ORCID Profile
0000-0001-5957-2490
Current Organisations
Southern Cross University
,
University of Technology Sydney
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Publisher: Wiley
Date: 10-1996
DOI: 10.1111/J.1539-6924.1996.TB00815.X
Abstract: Characterizing the dose-effect relationship and estimating acceptable exposure levels are the primary goals of quantitative risk assessment. A semiparametric approach is proposed for risk assessment with continuously measured or quantitative outcomes which has advantages over existing methods by requiring fewer assumptions. The approach is based on pairwise ranking between the response values in the control group and those in the exposed groups. The work generalizes the rank-based Wilcoxon-Mann-Whitney test, which for the two-group comparison is effectively a test of whether a response from the control group is different from (larger than) a response in an exposed group. We develop a regression framework that naturally extends this metric to model the dose effect in terms of a risk function. Parameters of the regression model can be estimated with standard software. However, inference requires an additional step to estimate the variance structure of the estimated parameters. An effective dose (ED) and associated lower confidence limit (LED) are easily calculated. The method is supported by a simulation study and is illustrated with a study on the effects of aconiazide. The method offers flexible modeling of the dose effect, and since it is rank-based, it is more resistant to outliers, nonconstant variance, and other departures from normality than previously described approaches.
Publisher: Wiley
Date: 09-2001
DOI: 10.1111/J.0006-341X.2001.00671.X
Abstract: We describe a method for assessing dose-response effects from a series of case-control and cohort studies in which the exposure information is interval censored. The interval censoring of the exposure variable is dealt with through the use of retrospective models in which the exposure is treated as a multinomial response and disease status as a binary covariate. Polychotomous logistic regression models are adopted in which the dose-response relationship between exposure and disease may be modeled in a discrete or continuous fashion. Partial conditioning is possible to eliminate some of the nuisance parameters. The methods are applied to the motivating study of the relationship between chorionic villus s ling and the occurrence of terminal transverse limb reduction.
Publisher: Environmental Health Perspectives
Date: 04-2005
DOI: 10.1289/EHP.7436
Abstract: Our recent study showed a dose-response relationship between environmental tobacco smoke (ETS) and the risk of early pregnancy loss. Smoking is known to affect female reproductive hormones. We explored whether ETS affects reproductive hormone profiles as characterized by urinary pregnanediol-3-glucuronide (PdG) and estrone conjugate (E1C) levels. We prospectively studied 371 healthy newly married nonsmoking women in China who intended to conceive and had stopped contraception. Daily records of vaginal bleeding, active and passive cigarette smoking, and daily first-morning urine specimens were collected for up to 1 year or until a clinical pregnancy was achieved. We determined the day of ovulation for each menstrual cycle. The effects of ETS exposure on daily urinary PdG and E1C levels in a +/-10 day window around the day of ovulation were analyzed for conception and nonconception cycles, respectively. Our analysis included 344 nonconception cycles and 329 conception cycles. In nonconception cycles, cycles with ETS exposure had significantly lower urinary E1C levels (beta = -0.43, SE = 0.08, p < 0.001 in log scale) compared with the cycles without ETS exposure. There was no significant difference in urinary PdG levels in cycles having ETS exposure (beta = -0.07, SE = 0.15, p = 0.637 in log scale) compared with no ETS exposure. Among conception cycles, there were no significant differences in E1C and PdG levels between ETS exposure and nonexposure. In conclusion, ETS exposure was associated with significantly lower urinary E1C levels among nonconception cycles, suggesting that the adverse reproductive effect of ETS may act partly through its antiestrogen effects.
Publisher: American Diabetes Association
Date: 12-07-2014
DOI: 10.2337/DC13-2625
Abstract: We investigated microvascular event risk in people with type 2 diabetes and assessed whether N-terminal pro–B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT) improved prediction. We performed a case-cohort study, including 439 incident cases of microvascular events (new or worsening nephropathy or retinopathy) and 2,946 noncase subjects identified from participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. NT-proBNP and hsTnT were measured in stored plasma s les using automated commercial assays. After adjustment for age, sex, and randomized treatment, the hazard ratios for microvascular events per 1-SD increase in the log-transformed hsTnT and NT-proBNP were 1.67 (95% CI 1.51–1.85) and 1.63 (1.44–1.84), respectively. After further adjustment for classical and diabetes-related cardiovascular disease risk factors, the hazard ratios attenuated to 1.40 (1.24–1.58) and 1.41 (1.24–1.60), respectively. While the C statistic did not improve on addition of hsTnT or NT-proBNP for the total microvascular end point, a combination of both markers improved the prediction of nephropathy (P = 0.033) but not retinopathy (P = 0.72). The corresponding net reclassification indices in a three–risk category model (& %, 10–15%, and & % 5-year risk) for all microvascular events were 7.31% (95% CI 2.24–12.79) for hsTNT addition, 6.23% (1.74–11.5) for NT-proBNP addition, and 7.1% (1.5–12.9) for both markers together. These data suggest that cardiac biomarkers moderately improve microvascular event risk prediction, in particular the risk of nephropathy. Further studies examining the value of this approach for trial design and clinical use are warranted.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-1992
DOI: 10.1097/00000421-199210000-00007
Abstract: EST 2287 was a Phase II clinical trial conducted by the Eastern Cooperative Oncology Group (ECOG) designed to evaluate trimetrexate in patients with advanced, measurable, inoperable squamous cell carcinoma of the esophagus. The drug was given at a dose of 12 mg/m2 daily for 5 days every 21 days to patients with carcinoma of the esophagus. The purpose of this study was to evaluate treatment efficacy in terms of tumor response and to assess the toxicity. According to a two-stage stopping rule, the study closed after 15 patients had entered. There were no responses to treatment, and median survival from study entry was 4.3 months. There was one treatment-related death caused by infection. One patient experienced life-threatening hematologic toxicity. Overall severe or worse toxicity occurred in more than half of the patients. It is concluded that additional trials of trimetrexate at this dose and schedule in patients with carcinoma of the esophagus are not warranted.
Publisher: Wiley
Date: 25-06-2013
DOI: 10.1002/ENV.2217
Publisher: Oxford University Press (OUP)
Date: 06-2000
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-1998
DOI: 10.1097/00043764-199812000-00002
Abstract: Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels, as well as urinary levels of FSH, LH, and E1C, a metabolite of testosterone, were measured to investigate the adverse reproductive effects of organophosphate pesticides among Chinese factory workers who were occupationally exposed to ethylparathion and methamidophos. Thirty-four exposed workers were randomly chosen and recruited from a large pesticide factory, and 44 unexposed workers were selected from a nearby textile factory. A quantitative pesticide exposure assessment was performed among a subset of the exposed and unexposed workers. Information on potential confounders was collected in an interview. A single blood s le was collected at the end of a work shift, when each subject also donated a semen s le. Three first-voided urine s les were collected from each worker on 3 consecutive days. Urinary p-nitrophenol level at 1 hour after the work shift correlated with serum (r = 0.71, P < 0.01) and urinary (r = 0.51, P = 0.04) FSH levels. Stratifying by the subjects' exposure status, we found a significant negative correlation among the exposed group between urinary FSH level and sperm count (r = -0.61, P < 0.01) and between urinary FSH level and sperm concentration (r = -0.53, P = 0.03). Pesticide exposure alone was significantly associated with serum LH level (beta [coefficient of exposure effect] = 0.79 95% confidence interval [CI] = 0.42, 1.16) but not with serum FSH or testosterone or with any urinary hormone levels. With adjustment for age, rotating shift work, current cigarette smoking, and current alcohol consumption, exposure significantly increased the serum LH level by 1.1 mIU/mL (95% CI = 0.34, 1.82). Meanwhile, the serum FSH level was slightly elevated (beta [coefficient of exposure effect] = 1.38 95% CI = -0.09, 2.85) and the serum testosterone level was decreased (beta = -55.13 95% CI = -147.24, 37) with increased pesticide exposure. Age and rotating shift work appeared to act as confounders. We conclude that organophosphate pesticides have a small effect on male reproductive hormones, suggestive of a secondary hormonal disturbance after testicular damage.
Publisher: Massachusetts Medical Society
Date: 08-09-1988
DOI: 10.1056/NEJM198809083191001
Abstract: Pain is highly prevalent in frail older people who often have multiple co-morbidities and multiple medicines. Rational prescribing of analgesics in frail older people is complex due to heterogeneity in drug disposition, comorbid medical conditions, polypharmacy and variability in analgesic response in this population. A critical issue in managing older people with pain is the need for judicious choice of analgesics based on a comprehensive medical and medication history. Care is needed in the selection of analgesic medicine to avoid drug-drug or drug-disease interactions. People living with dementia and cognitive impairment have suboptimal pain relief which in part may be related to altered pharmacodynamics of analgesics and challenges in the systematic assessment of pain intensity in this patient group. In the absence of rigorously controlled trials in frail older people and those with cognitive impairment a pharmacologically-guided approach can be used to optimize pain management which requires a systematic understanding of the pharmacokinetics and pharmacodynamics of analgesics in frail older people with or without changes in cognition.
Publisher: Wiley
Date: 12-1999
DOI: 10.1111/J.1749-6632.1999.TB08086.X
Abstract: This paper discusses some of the statistical issues that arise from developmental toxicity studies, wherein pregnant mice are exposed to chemicals in order to assess possible adverse effects on developing fetuses. We begin with a review of some current approaches to risk assessment, based on NOAELs, and provide justification for the use of methods based on dose-response models. Due to the hierarchical nature of the data, such models are more complicated in the present context than, say, in cancer studies. For ex le, multivariate binary outcomes arise when each fetus in a litter is assessed for the presence of malformations and/or low birth weight. We describe a multivariate exponential family model that works well for these data and that is flexible in terms of allowing response rates to depend on cluster side. Maximum likelihood estimation of model parameters and the construction of score tests for dose effect are briefly discussed. Results are illustrated with data from several NTP studies.
Publisher: Oxford University Press (OUP)
Date: 24-06-2003
Abstract: We propose a Bayesian model for physiologically based pharmacokinetics of 1,3-butadiene (BD). BD is classified as a suspected human carcinogen and exposure to it is common, especially through cigarette smoke as well as in urban settings. The main aim of the methodology and analysis that are presented here is to quantify variability in the rates of BD metabolism by human subjects. A three-compartmental model is described, together with informative prior distributions for the population parameters, all of which represent real physiological variables. The model is described in detail along with the meanings and interpretations of the associated parameters. A four-compartment model is also given for comparison. Markov chain Monte Carlo methods are described for fitting the model proposed. The model is fitted to toxicokinetic data obtained from 133 healthy subjects (males and females) from the four major racial groups in the USA, with ages ranging from 19 to 62 years. Subjects were exposed to 2 parts per million of BD for 20 min through a face mask by using a computer-controlled exposure and respiratory monitoring system. Stratification by ethnic group results in major changes in the physiological parameters. Sex and age were also tested but not found to have a significant effect.
Publisher: Wiley
Date: 24-06-2022
DOI: 10.1002/STA4.462
Abstract: Evidence from animal models and epidemiological studies has linked prenatal alcohol exposure (PAE) to a broad range of long‐term cognitive and behavioural deficits. However, there is a paucity of evidence regarding the nature and levels of PAE associated with increased risk of clinically significant cognitive deficits. To derive robust and efficient estimates of the effects of PAE on cognitive function, we have developed a hierarchical meta‐analysis approach to synthesize information regarding the effects of PAE on cognition, integrating data on multiple outcomes from six U.S. longitudinal cohort studies. A key assumption of standard methods of meta‐analysis, effect sizes are independent, is violated when multiple intercorrelated outcomes are synthesized across studies. Our approach involves estimating the dose–response coefficients for each outcome and then pooling these correlated dose–response coefficients to obtain an estimated “global” effect of exposure on cognition. In the first stage, we use in idual participant data to derive estimates of the effects of PAE by fitting regression models that adjust for potential confounding variables using propensity scores. The correlation matrix characterizing the dependence between the outcome‐specific dose–response coefficients estimated within each cohort is then run, while accommodating incomplete information on some outcome. We also compare inferences based on the proposed approach to inferences based on a full multivariate analysis.
Publisher: American Diabetes Association
Date: 2000
Abstract: While small clinical trials have shown that improved glycemic control reduces the risk of progression of microalbuminuria to proteinuria, two recent clinical trials did not confirm this finding. We sought to reconcile the contradictory evidence by examining the dose-response relationship between hyperglycemia and progression of microalbuminuria to proteinuria in in iduals with type 1 diabetes and microalbuminuria (n = 312) who were followed for 4 years with repeated assessments of urinary albumin excretion. Since 33 patients did not participate in follow-up (10.6%), data for 279 patients were analyzed. Urinary albumin excretion level worsened to proteinuria in 40 (4.1 per 100 person-years). To examine the dose-response relationship, baseline HbA1c was ided into four roughly equal groups using the cut points 8, 9, and 10%. The incidence rate varied significantly among the four groups (P = 0.008). Among those with HbA1c & .0%, the incidence rate of progression was only 1.3 per 100 person-years, while it was 5.1, 4.2, and 6.7 per 100 person-years in the three other groups. We used generalized additive models to examine the dose-response curve using HbA1c as a continuous variable and found that the risk of progression rises steeply between an HbA1c of 7.5-8.5% and then remains approximately constant across higher levels. In conclusion, the results of this study suggest that, in patients with microalbuminuria, the risk of progression to overt proteinuria can be reduced by improved glycemic control only if the HbA1c is maintained below 8.5%. Moreover, below that value, the risk declines as the level of HbA1c decreases.
Publisher: Informa UK Limited
Date: 2004
DOI: 10.1080/13547500400010122
Abstract: Little is known about the relevance of genetic polymorphisms to arsenic-related bladder cancer. A preliminary case-control study was conducted to explore the association between genetic polymorphisms of GSTT1, p53 codon 72 and bladder cancer in southern Taiwan, a former high arsenic exposure area. Fifty-nine urinary transitional cell carcinoma (TCC) patients from a referral centre in south-western Taiwan and 81 community controls matched on residence were recruited from 1996 to 1999. A questionnaire was administered to obtain arsenic exposure and general health information. Genotypes of p53 codon 72 and GSTT1 were analysed by polymerase chain reaction-restriction fragment length polymerase. The combined variant genotypes (heterozygous or homozygous variant) of p53 codon 72 and GSTT1 null were observed in 29% of cases and in 44% of controls, respectively. In this preliminary study, bladder cancer risk was slightly elevated for subjects carrying the variant genotype of p53 codon 72 or in subjects carrying the GSTT1 null genotype. Variants in p53 codon 72 increased the risk of bladder cancer among smokers. However, the results were not statistically significant and larger confirmatory studies are needed to clarify the role of candidate gene polymorphisms and bladder cancer risk in arsenic exposed populations.
Publisher: JSTOR
Date: 12-1993
DOI: 10.2307/2532254
Publisher: BMJ
Date: 27-10-2011
DOI: 10.1136/EMERMED-2011-200230
Abstract: To describe the incidence, characteristics and outcomes of patients with influenza-like symptoms presenting to 27 public hospital emergency departments (EDs) in Queensland, Australia. A descriptive retrospective study covering 5 years (2005-9) of historical data from 27 hospital EDs was undertaken. State-wide hospital ED Information System data were analysed. Annual comparisons between influenza and non-influenza cases were made across the southern hemisphere influenza season (June-September) each year. Influenza-related presentations increased significantly over the 5 years from 3.4% in 2005 to 9.4% in 2009, reflecting a 276% relative increase. Differences over time regarding characteristics of patients with influenza-like symptoms, based on the influenza season, occurred for admission rate (decreased over time from 28% in 2005 to 18% in 2009), length of stay (decreased over time from a median of 210 min in 2005 to 164 min in 2009) and access block (increased over time from 33% to 41%). Also, every year there was a significantly (p<0.001) higher percentage of access block in the influenza cohort than in the non-influenza cohort. Although there was a large increase over time in influenza-related ED presentations, most patients were discharged home from the ED. Special consideration of health service delivery management (eg, establishing an 'influenza clinic border protection and public rollout of vaccination, beginning with those most at risk') for this group of patients is warranted but requires evaluation. These results may inform planning for service delivery models during the influenza season.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2003
Publisher: Wiley
Date: 2001
DOI: 10.1002/SIM.993
Abstract: We discuss the use of local likelihood methods to fit proportional hazards regression models to right and interval censored data. The assumed model allows for an arbitrary, smoothed baseline hazard on which a vector of covariates operates in a proportional manner, and thus produces an interpretable baseline hazard function along with estimates of global covariate effects. For estimation, we extend the modified EM algorithm suggested by Betensky, Lindsey, Ryan and Wand. We illustrate the method with data on times to deterioration of breast cosmeses and HIV-1 infection rates among haemophiliacs.
Publisher: Informa UK Limited
Date: 06-1995
Publisher: Wiley
Date: 09-07-2008
DOI: 10.1002/SIM.3324
Publisher: SAGE Publications
Date: 04-2006
DOI: 10.1191/0962280206SM434OA
Abstract: Women tend to repeat reproductive outcomes, with past history of an adverse outcome being associated with an approximate two-fold increase in subsequent risk. These observations support the need for statistical designs and analyses that address this clustering. Failure to do so may mask effects, result in inaccurate variance estimators, produce biased or inefficient estimates of exposure effects. We review and evaluate basic analytic approaches for analysing reproductive outcomes, including ignoring reproductive history, treating it as a covariate or avoiding the clustering problem by analysing only one pregnancy per woman, and contrast these to more modern approaches such as generalized estimating equations with robust standard errors and mixed models with various correlation structures. We illustrate the issues by analysing a s le from the Collaborative Perinatal Project dataset, demonstrating how the statistical model impacts summary statistics and inferences when assessing etiologic determinants of birth weight.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2003
DOI: 10.1097/01.JOM.0000058336.05741.E8
Abstract: Arsenic is a known carcinogen, but data are especially lacking on the health effects of low-level exposure, and on the health significance of methylation ability. We conducted a case-control study (76 cases and 224 controls from 1996 to 1999) in southwestern Taiwan to explore the association among primary and secondary arsenic methylation index (PMI and SMI, respectively), cumulative arsenic exposure (CAE), and the risk of skin cancer. As compared with the controls, the skin cancer group reported more sun exposure (P = 0.02) and had a lower BMI (P = 0.03), as well as lower education level (P = 0.01). Skin cancer patients and controls were similar with regard to age, gender, smoking and alcohol consumption. Given a low SMI ( 15 mg/L-year was associated with an increased risk of skin cancer (OR, 7.48 95% CI, 1.65-33.99) compared to a CAE < or = 2 mg/L-year. Given the same level of PMI, SMI, and CAE, men had a higher risk of skin cancer (OR, 4.04 95% CI, 1.46-11.22) when compared to women. Subjects with low SMI and high CAE have a substantially increased risk of skin cancer. Males in all strata of arsenic exposure and methylation ability had a higher risk of skin cancer than women.
Publisher: Oxford University Press (OUP)
Date: 15-05-1996
Abstract: Phase II studies of fluorouracil (5-FU) administered by protracted intravenous infusion have suggested an improved response rate and decreased toxicity profile when compared with 5-FU given by bolus injection in patients with metastatic colorectal cancer. Additional studies have suggested further enhancement of infusion 5-FU activity when it is combined with low-dose weekly cisplatin administration. This phase III study in adults with metastatic colorectal cancer was planned as a comparison of objective response rates, toxicity, and survival in patients receiving bolus versus protracted-infusion 5-FU with or without cisplatin. Four hundred ninety-seven previously untreated patients with advanced, measurable metastatic colorectal cancer were randomly assigned to receive treatment A (bolus 5-FU at 500 mg/m2 for 5 days followed in 2 weeks by weekly bolus 5-FU at 600 mg/m2), treatment B (bolus 5-FU at 500 mg/m2 for 5 days followed in 2 weeks by weekly bolus 5-FU at 600 mg/m2, plus weekly cisplatin at 20 mg/m2), treatment C (5-FU at 300 mg/m2 per day by continuous infusion), or treatment D (5-FU at 300 mg/m2 per day by continuous infusion plus weekly cisplatin at 20 mg/m2). All drugs were administered intravenously. Enrollment in the trial occurred from August 1987 through December 1990, and follow-up was through September 1995. The Kaplan-Meier method was used to estimate overall and disease-free survival, and Cox regression models were used to assess the effects of patient characteristics on survival. All P values resulted from two-sided tests. Objective tumor response was observed in 28 (18%) of 153 patients receiving treatment A, in 45 (28%) of 159 patients receiving treatment C (C versus A P = .045), and in 47 (31%) of 153 patients receiving treatment D (D versus A P = .016). Because of excessive toxicity, treatment B was discontinued after only 12 patients had begun treatment. Median time to disease progression was 5.1 months for patients in arm A compared with 6.2 and 6.5 months for patients in arms C and D, respectively (C versus A, P = .007 D versus A, P = .017). Patterns of toxic effects differed substantially among the treatment arms. Forty-five percent of the patients receiving bolus 5-FU alone (A) experienced grade 3-4 leukopenia, with two sepsis-related deaths. Hand-foot syndrome and mucositis were the major treatment-limiting toxic effects for patients in the two treatment arms involving infusion. Despite the improvement in response rates and time to disease progression with infusion 5-FU with or without cisplatin (C and D, respectively) (P = .003), the overall survival for the three groups (A, C, and D) was similar (P = .307). This may have been due in part to a longer median survival time of 10.4 months for patients in arm A, compared with an anticipated survival of 7 months. 5-FU given as a continuous infusion produced a higher objective response rate, a modest prolongation in time to disease progression, and less life-threatening myelosuppression in patients than bolus 5-FU. Concomitant treatment with low-dose cisplatin caused added toxicity and complexity of treatment and did not provide a major clinical benefit. No statistically significant survival differences were observed among the three treatment groups.
Publisher: Springer Science and Business Media LLC
Date: 19-01-2010
Publisher: JSTOR
Date: 06-1985
DOI: 10.2307/2530877
Publisher: Elsevier BV
Date: 11-2003
Abstract: Low maternal prepregnancy BMI is associated with adverse birth outcomes, but the BMI at which risk increases is not well defined. We assessed whether the relationship between prepregnancy BMI and birth outcomes is influenced by the extent to which mothers were underweight in a prospective study in Anhui, China. The women (n = 575) were 20-34 y old, married, nulliparous and nonsmokers. All measures of infant growth increased with increasing maternal BMI until a plateau was reached at a BMI of 22-23 kg/m2. Infants born to the 27% of women who were severely underweight before pregnancy (BMI < or = 18.5 kg/m2) were at increased risk for fetal growth deficits associated with infant morbidity. Compared with a normal BMI, being severely underweight was associated with mean (+/- SEM) reductions of 219 +/- 40 g in infant birthweight and 6.7 +/- 1.3% in the birthweight ratio and an 80% increase in risk of intrauterine growth restriction [odds ratio (OR) 1.8 95% CI: 1.0, 3.3 P = 0.05]. Being severely underweight was also associated with smaller infant head circumference and lower ponderal index. Being moderately underweight (18.5 < BMI < 19.8 kg/m2) was not significantly associated with adverse pregnancy outcomes. Gestational age and risk of preterm birth were not associated with maternal BMI. More than half of the women in this study were underweight before pregnancy. Although being moderately underweight was not associated with increased risk of adverse pregnancy outcomes, being severely underweight was an important risk factor for reduced fetal growth.
Publisher: Informa UK Limited
Date: 12-2001
Publisher: Oxford University Press (OUP)
Date: 05-07-2021
DOI: 10.1111/RSSA.12716
Abstract: Propensity score methodology has become increasingly popular in recent years as a tool for estimating causal effects in observational studies. Much of the related research has been directed at settings with binary or discrete exposure variables with more recent work involving continuous exposure variables. In environmental epidemiology, a substantial proportion of in iduals is often completely unexposed while others may experience heavy exposure leading to an exposure distribution with a point mass at zero and a heavy right tail. We suggest a new approach to handle this type of exposure data by constructing a propensity score based on a two-part model and show how this model can be used to more reliably adjust for covariates of a semi-continuous exposure variable. We also consider the case when a misspecified propensity score is used in a regression adjustment and derive an explicit form of the bias. We show that the potential bias gets smaller as the estimated propensity score gets closer to the true expectation of the exposure variable given a set of observed covariates. While this result pertains to a more general setting, we use it to evaluate the potential bias in settings in which the true exposure has a semi-continuous structure. We also evaluate and compare the performance of our proposed method through simulation studies relative to a simpler linear regression-based propensity score for a continuous exposure variable as well as through direct covariate adjustment. Overall, we find that using a propensity score constructed via a two-part model significantly improves the regression estimate when the exposure variable is semi-continuous in nature. Specifically when the proportion of non-exposed subjects is high and the effects of covariates on exposure and outcome are strong, the proposed two-part propensity score method outperforms the more standard competing methods. We illustrate our method using data from the Detroit Longitudinal Cohort Study in which the exposure variable reflects gestational alcohol exposure featuring zero values and a long tail.
Publisher: Oxford University Press (OUP)
Date: 12-2016
DOI: 10.1111/J.1740-9713.2016.00982.X
Abstract: Making effective public policy decisions is challenging at the best of times, but especially in the context of environmental regulation, which typically requires managing opposing interests and strong opinions from industry and private citizens. In this case study, Louise Ryan, Matt Wand and Alan Malecki show how statistical analysis can help resolve conflict and inform effective decision-making under uncertainty
Publisher: Elsevier BV
Date: 12-1989
DOI: 10.1016/0360-3016(89)90536-1
Abstract: A Phase I-II trial testing the addition of systemic cisplatin (CDDP) to local hyperthermia and radiation was conducted to determine the dose of cisplatin that is tolerable once weekly for 6 weeks and to estimate the therapeutic potential of this trimodality combination in patients with locally advanced malignancies. Cisplatin at 20 mg/m2 (4 patients), 30 mg/m2 (8 patients), and 40 mg/m2 (12 patients) was given rapidly (over 5-10 min) i.v. after prehydration with 1 liter of normal saline. After approximately two-thirds of the cisplatin dose had been delivered, microwave hyperthermia was begun and continued for 60 min the target minimum tumor temperature was 43 degrees C. Following hyperthermia, a 400 cGy fraction of radiation was delivered to the tumor. On other days during the treatment weeks, additional 200 cGy fractions were given to total doses of 6,000-6600 cGy in patients with full radiation tolerance or 2400-3600 cGy in patients with limited radiation tolerance. The 24 patients in this trial had a median age of 57 years and the predominant sites/tumor types were head and neck/squamous cell carcinoma (9) and chest wall/breast adenocarcinoma (9). Seventeen of the 24 treated tumors (70%) had previously been irradiated. Eighteen patients (75%) had received prior chemotherapy and nine patients (38%) had previously been treated with cisplatin. Bone marrow suppression was dose limiting in patients heavily pretreated with chemotherapy and chest wall radiation. No significant toxicities were observed at the 20 and 30 mg/m2 dose levels, but 5 of the 12 patients (42%) treated at 40 mg/m2 required modification of the cisplatin dose because of blood count suppression in four patients and mild renal dysfunction in one patient. Each of the patients with bone marrow suppression, however, had been heavily pretreated except for one patient with thrombocytopenia due to hypersplenism. Nausea and vomiting were mild with use of a standard, multiagent antiemetic regimen. Twelve patients (50%) attained a complete regression (CR) and 12 patients (50%) a partial regression (PR). Complete regression appeared to correlate with small tumor volumes (115 cc for CR versus 199 cc for PR patients) and higher tumor temperatures (4.6 average minimum equivalent minutes at 43 degrees C in CR versus 2.0 min in PR patients). Local toxicities included second degree burns in 12 patients (50%) and third degree burns in 6 (25%), but all burns healed in 4-12 weeks without surgical intervention.(ABSTRACT TRUNCATED AT 400 WORDS)
Publisher: Informa UK Limited
Date: 09-2003
Publisher: SAGE Publications
Date: 06-2004
DOI: 10.1191/0962280204SM364RA
Abstract: This article discusses the growing interest in the use of biomarker data in environmental health research and considers some of the challenging statistical issues that arise. We specify a modeling framework that links environmental exposure, biomarkers and outcome, and discuss in conceptual terms how such a formulation could be used to inform dose response modeling for the purpose of quantitative risk assessment. We then analyse some biomarker data from a case-control study designed to elucidate the mechanisms of smoking induced lung cancer. Because of s le size limitations, we use a likelihood-based analysis which subsumes both cohort and case-control designs as special cases. Our analysis allows us to 1) investigate the extent to which the markers explain the pathway from exposure to outcome 2) quantify the degree to which biomarker data can improve on predicting outcome over and above exposure and 3) estimate the association among multiple markers.
Publisher: Informa UK Limited
Date: 09-1992
Publisher: Informa UK Limited
Date: 08-2002
Publisher: Wiley
Date: 2000
DOI: 10.1002/1097-0274(200011)38:5<555::AID-AJIM8>3.0.CO;2-E
Abstract: An exploratory, cross-sectional retrospective study was conducted to examine the effects of benzene exposure on menstrual problems. The study was based on a survey administered to over 3,000 women who worked in a large petrochemical company in Beijing, China. An abnormal menstrual cycle length (AMCL), defined as an average menstrual cycle length of greater than 35 days or less than 21 days, is the major outcome of interest. After 7 years of benzene exposure, the adjusted odds ratio of having AMCL for each additional 5 years of exposure was 1.71 (95% CI 1.27-2.31). Feeling stressed at work was also an important predictor. This study suggests a significant association of benzene exposure and perceived stress with menstrual disturbance. A prospective study is needed to confirm this finding.
Publisher: Wiley
Date: 06-2002
Abstract: To develop a method for predicting concurrently both hospital survival and length of stay (LOS) for seriously ill or injured patients, with particular attention to the competing risks of death or discharge alive as determinants of LOS. Previously collected 1995-1996 registry data on 2,646 cases of injured patients from three trauma centers in Maine. Time intervals were determined for which the rates of discharge or death were relatively constant. Poisson regression was used to develop a model for each type of terminal event, with risk factors on admission contributing proportionately to the subsequent rates for each outcome in each interval. Mean LOS and cumulative survival were calculated from a combination of the resulting piecewise exponential models. Age, Glasgow Coma Scale, Abbreviated Injury Scores, and specific mechanisms of injury were significant predictors of the rates of death and discharge, with effects that were variable in different time intervals. Predicted probability of survival and mean LOS from the model were similar to actual values for categorized patient groups. Piecewise exponential models may be useful in predicting LOS, especially if determinants of mortality are separated from determinants of discharge alive.
Publisher: Informa UK Limited
Date: 03-2004
Publisher: American Chemical Society (ACS)
Date: 23-05-2006
DOI: 10.1021/ES052477M
Abstract: Multi-tiered s ling approaches are common in environmental and occupational exposure assessment, where exposures for a given in idual are often modeled based on simultaneous measurements taken at multiple indoor and outdoor sites. The monitoring data from such studies is hierarchical by design, imposing a complex covariance structure that must be accounted for in order to obtain unbiased estimates of exposure. Statistical methods such as structural equation modeling (SEM) represent a useful alternative to simple linear regression in these cases, providing simultaneous and unbiased predictions of each level of exposure based on a set of covariates specific to the exposure setting. We test the SEM approach using data from a large exposure assessment of diesel and combustion particles in the U.S.trucking industry. The exposure assessment includes data from 36 different trucking terminals across the United States s led between 2001 and 2005, measuring PM2.5 and its elemental carbon (EC), organic carbon (OC) components, by personal monitoring, and s ling at two indoor work locations and an outdoor "background" location. Using the SEM method, we predict the following: (1) personal exposures as a function of work-related exposure and smoking status (2) work-related exposure as a function of terminal characteristics, indoor ventilation, job location, and background exposure conditions and (3) background exposure conditions as a function of weather, nearby source pollution, and other regional differences across terminal sites. The primary advantage of SEMs in this setting is the ability to simultaneously predict exposures at each of the s ling locations, while accounting for the complex covariance structure among the measurements and descriptive variables. The statistically significant results and high R2 values observed from the trucking industry application supports the broader use of this approach in exposure assessment modeling.
Publisher: Wiley
Date: 24-07-2003
DOI: 10.1002/BDRA.10078
Abstract: An increased frequency of major limb malformations, especially terminal transverse limb defects, have been described in several studies of birth defects in children who had been exposed to the prenatal diagnosis procedure known as chorionic villus s ling (CVS). Vascular disruption has been proposed as the mechanism behind the fetal effect. We postulate that this mechanism is more likely to affect one or two middle fingers, rather than all five fingers. A recent report of the frequency of defects in any or all fingers in an unexposed control population enabled us to assess whether CVS is associated with an increased frequency of defects involving one or two fingers, as well as terminal transverse limb defects. The frequency of limb-reduction defects affecting one or more fingers or toes, including those with constriction rings and tissue loss, in published studies of 20,236 children who had been exposed to CVS was compared with the frequency in 161,252 newborn infants who had not been exposed to CVS. Children with recognized genetic disorders were excluded. Several aspects of the limb deficiencies were more common in the CVS-exposed infants than in unexposed controls. The former were more likely to have: 1) any type of limb deficiency involving one or more fingers (p < .001) 2) absence/ hypoplasia of two fingers (p < .001) and 3) absence/hypoplasia of all five fingers (p = .015). The absence of the distal portion of the third finger was a distinctive type of limb-reduction defect in CVS-exposed infants. The occurrence of deficiencies in one or two fingers, including those designated as "amniotic band deformities," are as common as terminal transverse limb defects in CVS-exposed infants, and both are much more common than in unexposed infants. The absence of the distal portion of the third finger, with tapering and stiff joints, appears to be a distinctive effect of exposure to CVS.
Publisher: Wiley
Date: 09-1999
DOI: 10.1002/(SICI)1097-0274(199909)36:3<379::AID-AJIM5>3.0.CO;2-8
Abstract: Serum paraoxonase has been associated with the metabolism of organophosphate pesticides in humans. Molecular analysis of the human paraoxonase gene (PON1) has revealed that Arg192 homozygotes have a greater detoxifying capability than Gln192 homozygotes. We examined the effects of PON1 genotypes on male reproductive outcomes and its interaction with exposure to organophosphate pesticides. We studied 60 Chinese pesticide-factory workers and 89 textile-factory workers who were unexposed to pesticides. The respective allele frequencies of Arg192 and Gln192 were 0.62 and 0.38. Pesticide exposure among 36 exposed subjects and 12 unexposed subjects, regardless of gender, was assessed by personal measurement of pesticide residues over an entire 8-hr shift and measurement of urinary p-nitrophenol level over a 24-hr period. We analyzed semen and hormone data collected from male subjects. When the three PON1 genotypes were analyzed separately, a gene dose effect was not detected. We used the unexposed Arg192 homo/heterozygotes as the reference group, and re-analyzed the data. Exposed Arg192 homo/heterozygotes had significantly lower sperm count (chi 2 = 9.01, P < 0.01) and lower percentage of sperm with normal morphology (chi 2 = 4.18, P < 0.05) than the reference group. Both unexposed Gln192 homozygotes (chi 2 = 4.90, P < 0.05) and exposed Arg192 homo/heterozygotes (chi 2 = 10.00, P < 0.01) showed significantly lower sperm concentrations than the reference group. In addition, exposed Arg192 homo/heterozygotes had significantly higher serum LH levels (chi 2 = 7.94, P < 0.01) than the reference group. Because of a small s le size, our findings are highly preliminary. Nevertheless, it calls for further investigation of the interaction between the PON1 genotype and organophosphate pesticide exposure on male reproductive outcomes.
Publisher: Environmental Health Perspectives
Date: 05-1997
DOI: 10.1289/EHP.97105514
Abstract: The relationship between maternal exposure to air pollution during periods of pregnancy (entire and specific periods) and birth weight was investigated in a well-defined cohort. Between 1988 and 1991, all pregnant women living in four residential areas of Beijing were registered and followed from early pregnancy until delivery. Information on in idual mothers and infants was collected. Daily air pollution data were obtained independently. The s le for analysis included 74,671 first-parity live births were gestational age 37-44 weeks. Multiple linear regression and logistic regression were used to estimate the effects of air pollution on birth weight and low birth weight (< 2,500 g), adjusting for gestational age, residence, year of birth, maternal age, and infant gender. There was a significant exposure-response relationship between maternal exposures to sulfur dioxide (SO2) and total suspended particles (TSP) during the third trimester of pregnancy and infant birth weight. The adjusted odds ratio for low birth weight was 1.11 (95% CI, 1.06-1.16) for each 100 micrograms/m3 increase in SO2 and 1.10 (95% CI, 1.05-1.14) for each 100 micrograms/m3 increase in TSP. The estimated reduction in birth weight was 7.3 g and 6.9 g for each 100 micrograms/m3 increase in SO2 and in TSP, respectively. The birth weight distribution of the high-exposure group was more skewed toward the left tail (i.e., with higher proportion of births < 2,500 g) than that of the low-exposure group. Although the effects of other unmeasured risk factors cannot be excluded with certainty, our data suggests that TSP and SO2, or a more complex pollution mixture associated with these pollutants, contribute to an excess risk of low birth weight in the Beijing population.
Publisher: American Society for Clinical Investigation
Date: 04-1995
DOI: 10.1172/JCI117814
Publisher: Wiley
Date: 11-12-2008
DOI: 10.1002/BDRA.20528
Abstract: Dominant hemimelia (Dh) is an autosomal dominant mutation that arose spontaneously in mice. Dh animals are asplenic and they exhibit asymmetric hindlimb defects in association with reduced numbers of lumbar vertebrae. These defects suggest that Dh acts early in embryonic development to affect patterning of the anterior-posterior (A-P) and left-right axes. This study was undertaken to determine whether retinoic acid (RA), which is involved in A-P patterning and coordination of bilaterally synchronized somitogenesis, affects phenotypic expression of the Dh gene. Thirty-four pregnant females were given, by oral intubation, a single dose of 50 or 75 mg all-trans RA per kilogram body weight at GD 9, 10, or 11. The pregnant females were then euthanized at GD 18 and fetuses removed by cesarean section. A total of 326 fetuses were identified by phenotype and linked DNA and their skeletons were analyzed. There was a differential effect of RA on the axial skeleton and hindlimb of Dh/+ mice as compared to their wild-type littermates. Dose- and stage-specific effects on sternebrae and vertebrae were observed. The effects of RA dosing on numbers of sternebrae and vertebrae suggest that Dh embryos have a primary defect in retinoid-mediated A-P patterning. Dosing with RA may produce the observed effects on phenotypic expression of Dh/+ by indirectly or directly modifying an already existing altered Hox expression pattern. As the relationship between axial patterning and the asymmetric limb is unknown, Dh is an important model for studying this relationship.
Publisher: Wiley
Date: 2004
DOI: 10.1002/SIM.1918
Abstract: Many authors in recent years have proposed extensions of familiar survival analysis methodologies to apply in dependent data settings, for ex le, when data are clustered or subject to repeated measures. However, these extensions have been considered largely in the context of right censored data. In this paper, we discuss a parametric frailty model for the analysis of clustered and interval censored failure time data. Details are presented for the specific case where the underlying time to event data follow a Weibull distribution. Maximum likelihood estimates will be obtained using commercially available software and the empirical efficiency of these estimators will be explored via a simulation study. We also discuss a score test to make inferences about the magnitude and significance of over-dispersion in clustered data settings. These methods will be illustrated using data from the East Boston Asthma Study.
Publisher: Massachusetts Medical Society
Date: 12-04-2001
Publisher: Elsevier BV
Date: 07-2007
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2005
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-1993
DOI: 10.1097/00001648-199303000-00011
Abstract: Over 1.5 billion prescriptions were filled by pharmacies in 1990, but little information exists on the effect that pharmaceutical agents have on female reproductive capacity. As part of a case-control study of risk factors for primary ovulatory infertility, we examined self-reported use of several prescription and nonprescription medications in 597 women with ovulatory infertility and 3,833 controls admitted for delivery at seven hospitals. Only women reporting use of a drug for at least 6 months, beginning before the onset of infertility in cases and before conception in controls, were considered exposed. An elevated risk of ovulatory infertility was found for women who ever used thyroid preparations [relative risk (RR) = 2.3, 95% confidence interval (CI) = 1.5-3.5] or antidepressants (RR = 2.9, 95% CI = 0.9-8.3), although the latter estimate was based on only five cases who reported having taken antidepressants. Current users of tranquilizers and ever-users for more than 2 years were also at greater risk of infertility than never-users (RR = 3.2, 95% CI = 1.1-8.5 and RR = 2.9, 95% CI = 0.8-11, respectively). Women who used asthma medication before age 21 had more than a twofold increase in risk of ovulatory infertility (RR = 2.5, 95% CI = 1.0-5.9).
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-1997
DOI: 10.1097/00005373-199706000-00025
Abstract: Mortality is an important measurement of injury outcomes, but measurements reflecting disability or cost are also important. Hospital length of stay (LOS) has been used as an outcome variable, but reduced LOS could be achieved either by improved care or by increased mortality. A solution to this statistical problem of "competing risks" would enable injury outcomes based on LOS to be modeled using time-to-event methods. Time-to-event methodology was applied to 2,106 cases with complete data from the 1991-1994 registry of a regional trauma center. LOS was used as the outcome variable, modified by assigning an arbitrarily long LOS to any fatal case. A combination of proportional hazards and logistic regression models was used to explore the effects of potential predictive variables, including Trauma Score (TS), Injury Severity Score (ISS), components of TS or ISS, age, sex, alcohol use, and whether a patient was transferred. The "TRISS" combination of TS, ISS, and age previously shown to predict mortality also predicted "modified LOS" (Wald p value less than 0.001 for each variable). Models using only age and certain components of ISS or TS fit our data even better, with fewer parameters. Other variables were not predictive. Modified Kaplan-Meier plots provided easily interpreted graphical results, combining both mortality and LOS information. With a simple modification to allow for competing risks, time-to-event methods enable more informative modeling of injury outcomes than binary (lived/died) methods alone. Such models may be useful for describing and comparing groups of hospitalized trauma patients.
Publisher: JSTOR
Date: 1993
DOI: 10.2307/2986233
Publisher: Environmental Health Perspectives
Date: 11-2009
DOI: 10.1289/EHP.0900840
Publisher: Hindawi Limited
Date: 2003
DOI: 10.1080/1357714031000114156
Abstract: Purpose Because we had observed in the synovial sarcoma subgroup of a broad phase III advanced soft tissue sarcoma study a significantly greater objective regression rate from ifosfamide+doxorubicin (88%) than from doxorubicin alone (20%) ( P = 0.02), the Eastern Cooperative Oncology Group (ECOG) decided to further assess this two drug combination in a subsequent Phase II study. Patients Between 1994 and 1999, twelve adult patients with advanced synovial sarcomas were enrolled to receive, as their initial chemotherapy, ifosfamide 7.5 gm/m 2 plus doxorubicin 60 mg/m 2 , given intravenously over two consecutive days every 3 weeks. Methods Each day for 2 days doxorubicin 30 mg/m 2 was infused over 5 min through a running i.v., followed by ifosfamide 3750 mg/m 2 over 4 h. Continuous i.v. fluid was infused at 300 mL/h for 3 h on day 1, before chemotherapy was begun then the infusion was continued at 100 mL/h for a total of 3 days. Mesna 750 mg/m 2 was given 15 min before ifosfamide and at 4 and 8 h after ifosfamide on days 1 and 2 of each treatment cycle. Filgrastim (G-CSF) 5 μg/kg was given subcutaneously each day for 14 days beginning on day 3 of each treatment cycle to limit the severity of neutropenia. Results Five of our 12 patients (42%) experienced partial regression of their advanced synovial sarcomas however, this first stage result was borderline for proceeding to the second planned stage of accrual and our case accrual was quite poor. Thus, the study was closed after stage one accrual. Our patients received a median of four cycles of chemotherapy (range: 1 to 6). All patients experienced at least grade 3 neutropenia (grade 4 in nine of them), and one patient died of treatment-related sepsis following the initial cycle of chemotherapy. Median survival was 11 months.
Publisher: Oxford University Press (OUP)
Date: 15-06-2001
Abstract: Tofu is a commonly consumed food in China. Tofu may interfere with lead absorption and retention because of its high calcium content. In this observational study, the authors examined whether dietary tofu intake was associated with blood lead levels among young adults in Shenyang, China. The analyses included 605 men and 550 women who completed baseline questionnaires and had blood lead measurements taken in 1996-1998 as part of a prospective cohort study on reproductive health. Mean blood lead levels were 13.2 microg/dl in men and 10.1 microg/dl in women. Blood lead levels were negatively associated with tofu intake in both genders. A linear trend test showed a 3.7% (0.5-microg/dl) decrease in blood lead level with each higher category of tofu intake (p = 0.003). The highest tofu intake group (> or =750 g/week) had blood lead levels 11.3% lower (95% confidence interval: 4.1, 18.0) than those of the lowest tofu intake group (<250 g/week). In all regression models, data were adjusted for gender, age, height, body mass index, district, cigarette smoking, alcohol drinking, education, occupation, use of vitamin supplements, season, and dietary intake of meat, fish, vegetables, eggs, and milk. In conclusion, the authors found a significant inverse dose-response relation between tofu consumption and blood lead levels in this Chinese population.
Publisher: Wiley
Date: 02-06-2017
DOI: 10.1002/SIM.7349
Abstract: Nonresponses and missing data are common in observational studies. Ignoring or inadequately handling missing data may lead to biased parameter estimation, incorrect standard errors and, as a consequence, incorrect statistical inference and conclusions. We present a strategy for modelling non-ignorable missingness where the probability of nonresponse depends on the outcome. Using a simple case of logistic regression, we quantify the bias in regression estimates and show the observed likelihood is non-identifiable under non-ignorable missing data mechanism. We then adopt a selection model factorisation of the joint distribution as the basis for a sensitivity analysis to study changes in estimated parameters and the robustness of study conclusions against different assumptions. A Bayesian framework for model estimation is used as it provides a flexible approach for incorporating different missing data assumptions and conducting sensitivity analysis. Using simulated data, we explore the performance of the Bayesian selection model in correcting for bias in a logistic regression. We then implement our strategy using survey data from the 45 and Up Study to investigate factors associated with worsening health from the baseline to follow-up survey. Our findings have practical implications for the use of the 45 and Up Study data to answer important research questions relating to health and quality-of-life. Copyright © 2017 John Wiley & Sons, Ltd.
Publisher: American Medical Association (AMA)
Date: 03-2002
DOI: 10.1001/ARCHPEDI.156.3.241
Abstract: It has been hypothesized that day care--related infections may explain the inverse relation between day care attendance in early life and asthma in childhood. To examine the relation between day care attendance or respiratory tract illnesses in the first year of life and wheezing and asthma in the first 4 years of life among children with a parental history of atopy who were followed up from birth. Day care attendance in the first year of life was inversely associated with geometric mean total serum IgE level (12.9 [+/-1 SD = 3.3, 51.4] IU/mL for day care vs 18.5 [[+/-1 SD = 5.3, 64.7] IU/mL for no day care P =.03) at 2 years of age but not significantly associated with wheezing at or after 2 years of age. Having at least 1 physician-diagnosed lower respiratory tract illness in the first year of life was significantly associated with recurrent wheezing (odds ratio [OR], 2.0 95% confidence interval [CI], 1.0-4.1) and asthma (OR, 2.5 95% CI, 1.1-5.5) at 4 years of age, but not with any wheezing (infrequent and frequent) at 3 years or older. Illnesses of the upper respiratory tract (> or = 1 physician-diagnosed upper respiratory tract illness or > or = 3 episodes of nasal catarrh) in the first year of life were associated with any wheezing (frequent and infrequent) between the ages of 1 and 4 years, but not with recurrent wheezing or asthma at 4 years of age. Our results suggest that among children with a parental history of atopy the protective effect of day care attendance in early life against the development of atopy has begun by 2 years of age, and that a protective effect of day care attendance in early life against wheezing may not be observed until after 4 years of age.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 1989
Abstract: European and American investigators have reported response rates of 38% to 83% for ifosfamide alone in pretreated sarcomas. In a phase II trial of ifosfamide 2.0g/m2 days 1 to 4 with mesna uroprotection in 124 patients with previously failed sarcomas, four (3%) responded completely (95% exact confidence interval, 1% to 8%) and 26 (21%) had a complete or partial response (95% exact confidence interval, 14% to 29%). The median time to progression was 5 and 9 months for partial and complete responders, respectively. In the subset of soft tissue sarcomas, the response rate for the patients receiving bolus administration was 26%, compared with 9% for the patients receiving a continuous infusion schedule (P = .03). The response rates among patients with soft tissue and bony sarcomas with a performance score of 0-2 and 0-1 prior to chemotherapy administration were 20% and 40%, respectively. Somnolence or confusion developed in 19%. Neurotoxicity was significantly associated with poor performance status (P less than .01), elevated creatinine (P less than .01), and low bicarbonate levels (P = .05). A serum bicarbonate less than 20 developed in 31% of the patients and was significantly associated with older age (P = .01), elevated creatinine (P = .02), and female sex (P = .06). Hematuria was significantly associated with no uroprotection (the first four patients did not receive mesna because it was unavailable), but was not associated with prior cyclophosphamide, pelvic radiotherapy, age, or bolus v continuation infusion schedule. Thus, ifosfamide is active in failed sarcomas and warrants further study in previously untreated patients with sarcoma.
Publisher: Wiley
Date: 08-1999
DOI: 10.1002/(SICI)1097-0274(199908)36:2<230::AID-AJIM2>3.0.CO;2-6
Abstract: A study of the prevalence of sperm aneuploidy among pesticide factory workers was conducted in Anhui, China. We recruited 75 men: 32 subjects from a large pesticide-manufacturing plant and 43 subjects from a nearby textile factory free of pesticide exposure. Each subject met the following criteria: age of 20-40 years continuous work in the plant for 3 months prior to the study, no congenital anomalies or acquired disease of the external genitalia and no history of recent febrile illness or mumps. Within one hour after collection from each subject, semen was evaluated in terms of several parameters and smear slides were prepared. Exposure assessment revealed that workers in the pesticide plant were exposed to ethyl parathion or methamidophos, each of which is a potent organophosphate pesticide, at a median level of 0.02 mg/m3 (8-hour time weighted average as measured by personal pump) while workers in the control plant had no such occupational exposure. Twenty-nine semen slides (13 from the exposed group and 16 from the unexposed group) were randomly chosen for aneuploidy scoring by the three-color fluorescence in situ hybridization (FISH) method with scorers being unaware of exposure status. Median semen parameters were as follows for exposed (and unexposed) men: abstinence period, 3 days (4 days) sperm concentration, 52.8x10(6)/ml (53.1x10(6)/ml) proportion of sperm with normal motility, 50.5% (61.3%) and proportion of sperm with normal morphology, 59% (61.5%). The specific chromosome abnormalities of interest were disomy for chromosome 18 and the three different types of sex chromosome disomy (i.e. XX, XY, YY disomy). The crude proportion of all aneuploidy combined was 0.30% and 0.19% for sperm from exposed and unexposed men, respectively. Poisson regression with overdispersion adjustment yielded significantly different crude risks of aneuploidy - 3.03 and 1.94 per 1,000 sperm from exposed and unexposed men, respectively - giving a rate ratio of 1.56 (95% CI, 1.06-2.31). The regression coefficients remained statistically significant after adjustment for inter-technician variability giving a rate ratio of 1.51 (95% CI, 1. 04-2.20). We conclude that occupational exposure to organophosphate pesticides moderately increases the prevalence of sperm aneuploidy.
Publisher: Springer Science and Business Media LLC
Date: 12-2003
Publisher: Oxford University Press (OUP)
Date: 09-2000
Publisher: Human Kinetics
Date: 10-2020
Abstract: Introduction : Assessments of executive functions (EFs) with varying levels of perceptual information or action fidelity are common talent-diagnostic tools in soccer, yet their validity still has to be established. Therefore, a longitudinal development of EFs in high-level players to understand their relationship with increased exposure to training is required. Methods : A total of 304 high-performing male youth soccer players (10–21 years old) in Germany were assessed across three seasons on various sport-specific and non-sport-specific cognitive functioning assessments. Results : The posterior means (90% highest posterior density) of random slopes indicated that both abilities predominantly developed between 10 and 15 years of age. A plateau was apparent for domain-specific abilities during adolescence, whereas domain-generic abilities improved into young adulthood. Conclusion : The developmental trajectories of soccer players’ EFs follow the general populations’ despite long-term exposure to soccer-specific training and game play. This brings into question the relationship between high-level experience and EFs and renders including EFs in talent identification questionable.
Publisher: Springer Science and Business Media LLC
Date: 28-01-2004
Publisher: Wiley
Date: 12-2020
DOI: 10.1111/INSR.12432
Publisher: Wiley
Date: 17-06-2016
DOI: 10.1002/GEPI.21986
Publisher: American Medical Association (AMA)
Date: 28-08-2002
DOI: 10.1001/ARCHPEDI.156.8.818
Abstract: Effective screening for exposure to violence (ETV) in the pediatric setting depends on informant reliability and recognition of patients at increased risk. Pediatricians screening for children's ETV often rely on parent reporting. That there would be poor caretaker-child concordance given that children would report events occurring outside the home not witnessed by the caretaker and that ETV would be higher among immigrant families. To examine concordance between caretaker and child self-report of the child's ETV in a preadolescent population and to explore factors related to increased risk. Community-based survey. Urban community health center. One hundred sixty-five caretaker-child pairs. The ETV was assessed by means of a standardized interview questionnaire on location and frequency of ETV. A Rasch model was used to develop summary scores of ETV (frequency and severity). Caretaker-child concordance on reports of child's ETV was poor. The kappa statistics ranged from -0.04 for seeing someone knifed to 0.39 for witnessing a shooting. Children reported ETV more often in their neighborhood or at school, whereas caretakers reported more events near or at home. Univariate predictors of child's self-reported ETV were female sex (beta +/- SE, -10.1 +/- 4.6 P =.03) and caretaker being orced (beta +/- SE, 12.6 +/- 6.0 P =.04). In multivariate analyses, country of origin predicted child's ETV, adjusting for child's age and sex, and caretaker educational status and marital status. Caretakers and their children have poor agreement on reports of the child's ETV. Intervention strategies around ETV should include assessment of the child independent of caretaker report for preadolescents. Screening may be more effective if pediatricians are aware of factors related to increased risk, including immigration status and caretaker marital status.
Publisher: Elsevier BV
Date: 12-2002
Abstract: To determine whether different alleles of the ADH2 gene (ADH2-1, ADH2-2 and ADH2-3) with differing levels of enzymatic activity can alter the risk of fetal alcohol effects. ADH2 genotypes were performed on 404 pregnant high-risk women and 139 infants as part of a larger study of alcohol use in pregnancy. Mothers were interviewed about alcohol use during pregnancy, and their infants were examined for alcohol-related features without knowledge of the exposure status. The ADH2-1/3 genotype was more prevalent among black women (46%) than expected (33%) the rate among white women was low as expected (2%). More black women who reported high alcohol use during the pregnancy had the ADH2-1/3 genotype compared with those who reported no alcohol use (70% vs 44%). Sixty percent of the affected black infants had the ADH2-1/3 genotype compared with 29% of the unaffected infants (P <.045). The maternal genotype correlated with her chance of having an infant with alcohol-related physical features (odds ratio = 2.49). This association remained significant after accounting for confounders, such as smoking and maternal weight gain. Alcohol exposure was not significantly associated with infant outcome in black infants after accounting for genotype, smoking, and maternal weight gain, but this association could only be tested in 10 infants of mothers with high exposure. Women with the ADH2-1/3 genotype may be at greater risk for having an affected infant, which may be the result of greater ingestion of alcohol.
Publisher: Oxford University Press (OUP)
Date: 07-11-2006
Abstract: The ubiquitous use of phthalate esters in plastics, personal care products and food packaging materials results in widespread general population exposure. In this report, we extend our preliminary study on the relationship between urinary concentrations of phthalate metabolites and sperm DNA damage among a larger s le of men and include measurements of mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), two oxidative metabolites of di-(2-ethylhexyl) phthalate (DEHP). Among 379 men from an infertility clinic, urinary concentrations of phthalate metabolites were measured using isotope-dilution high-performance liquid chromatography-tandem mass spectrometry. Sperm DNA damage measurements, assessed with the neutral comet assay, included comet extent (CE), percentage of DNA in tail (Tail%) and tail distributed moment (TDM). Monoethyl phthalate (MEP), a metabolite of diethyl phthalate, was associated with increased DNA damage, confirming our previous findings. Mono-(2-ethylhexyl) phthalate (MEHP), a metabolite of DEHP, was associated with DNA damage after adjustment for the oxidative DEHP metabolites. After adjustment for MEHHP, for an interquartile range increase in urinary MEHP, CE increased 17.3% [95% confidence interval (CI) = 8.7-25.7%], TDM increased 14.3% (95% CI = 6.8-21.7%) and Tail% increased 17.5% (95% CI = 3.5-31.5%). Sperm DNA damage was associated with MEP and with MEHP after adjusting for DEHP oxidative metabolites, which may serve as phenotypic markers of DEHP metabolism to 'less toxic' metabolites. The urinary levels of phthalate metabolites among these men were similar to those reported for the US general population, suggesting that exposure to some phthalates may affect the population distribution of sperm DNA damage.
Publisher: Wiley
Date: 03-2000
DOI: 10.1002/(SICI)1096-9926(200003)61:3<196::AID-TERA7>3.0.CO;2-T
Publisher: Oxford University Press (OUP)
Date: 29-04-2007
Publisher: American Public Health Association
Date: 2008
Abstract: Objectives. We assessed whether maternal depressive symptoms and parenting self-efficacy were associated with child growth delay. Methods. We collected data from a random s le of 595 low-income mothers and their children aged 6 to 24 months in Teresina, Piauí, Brazil, including information on sociodemographic characteristics, mothers’ depressive symptoms and parenting self-efficacy, and children’s anthropometric characteristics. We used adjusted logistic regression models in our analyses. Results. Depressive symptoms among mothers were associated with 1.8 times higher odds (95% confidence interval [CI] = 1.1, 2.9) of short stature among children. Parenting self-efficacy was not associated with short stature, nor did it mediate or modify the relationship between depressive symptoms and short stature. Maternal depressive symptoms and self-efficacy were not related to child underweight. Conclusions. Our results showed that among low-income Brazilian families maternal depressive symptoms, but not self-efficacy, were associated with short stature in children aged 6 to 24 months after adjustment for known predictors of growth.
Publisher: Wiley
Date: 07-1994
Abstract: The purpose of this paper is to demonstrate the application of generalized estimating equations to assess an exposure effect using multiple birth outcomes. This multivariate approach provides the flexibility of regression modeling and improved power, as compared to series of univariate analyses or collapsing the multiple end-points to a single indicator of affectedness. Motivating the discussion will be a large cohort study designed to assess the effects of anticonvulsant medications on a variety of birth outcomes, including major malformations, and growth and weight parameters, as well as a broad spectrum of minor physical anomalies. Because the study is still in progress, the aim here is not to present a definitive analysis, but to present and describe the application of these recently developed statistical methods to analyze studies with multiple outcomes. For simplicity, we will focus on the control and drug-exposed groups only from that study (ignoring the seizure history group), and we will concentrate on an analysis of minor physical anomalies.
Publisher: Informa UK Limited
Date: 12-1985
Publisher: Wiley
Date: 15-10-2011
DOI: 10.1002/1097-0142(19930515)71:10<2995::AID-CNCR2820711018>3.0.CO;2-P
Abstract: Each year, 6000 people die in the United States from metastatic melanoma. Further study of factors affecting the prognosis of patients with this disease is needed. The authors analyzed response and survival data from 635 patients who had entered three Eastern Cooperative Oncology Group trials for metastatic melanoma. Factors associated with poorer survival after study entry included poor performance status and the presence of symptoms, such as reduced appetite, fever, or nausea/vomiting. Male patients had poor survival, as did patients entering the study less than 1 year after a documented recurrence to study entry. As expected, characteristics of the initial primary disease (treatment and symptoms) had little association with survival after entering the advanced disease protocol. Two summary measures of the extent of metastatic involvement had a strong influence on survival. These were the number of nonbone metastases and the clinician's assessment as to the most significant metastatic site. Patients with the liver as their clinically most significant metastatic site had a poorer prognosis than those otherwise classified, including those with central nervous system metastases. The prognosis also worsened with an increasing number of sites of nonbone metastases, including skin and soft tissue. Tumor response occurred in only 11% of the patients. Patients with poor performance status and those with lung involvement had a significantly lower response rate than did others. Although the frequency of response was low, patients with objective responses survived significantly longer than did the nonresponders (based on an analysis appropriately adjusted for the time of response using a time-dependent proportional-hazards model). These results provide useful guidelines for the design and analysis of clinical trials in metastatic melanoma.
Publisher: Mary Ann Liebert Inc
Date: 12-2011
Publisher: Oxford University Press (OUP)
Date: 09-1997
Abstract: We propose a latent variable model for mixed discrete and continuous outcomes. The model accommodates any mixture of outcomes from an exponential family and allows for arbitrary covariate effects, as well as direct modelling of covariates on the latent variable. An EM algorithm is proposed for parameter estimation and estimates of the latent variables are produced as a by-product of the analysis. A generalized likelihood ratio test can be used to test the significance of covariates affecting the latent outcomes. This method is applied to birth defects data, where the outcomes of interest are continuous measures of size and binary indicators of minor physical anomalies. Infants who were exposed in utero to anticonvulsant medications are compared with controls.
Publisher: Springer Science and Business Media LLC
Date: 28-05-2009
Publisher: Wiley
Date: 06-2000
DOI: 10.1111/J.0006-341X.2000.00593.X
Abstract: We propose a scaled linear mixed model to assess the effects of exposure and other covariates on multiple continuous outcomes. The most general form of the model allows a different exposure effect for each outcome. An important special case is a model that represents the exposure effects using a common global measure that can be characterized in terms of effect sizes. Correlations among different outcomes within the same subject are accommodated using random effects. We develop two approaches to model fitting, including the maximum likelihood method and the working parameter method. A key feature of both methods is that they can be easily implemented by repeatedly calling software for fitting standard linear mixed models, e.g., SAS PROC MIXED. Compared to the maximum likelihood method, the working parameter method is easier to implement and yields fully efficient estimators of the parameters of interest. We illustrate the proposed methods by analyzing data from a study of the effects of occupational pesticide exposure on semen quality in a cohort of Chinese men.
Publisher: Oxford University Press (OUP)
Date: 1988
Publisher: Springer Science and Business Media LLC
Date: 08-05-2017
Publisher: Informa UK Limited
Date: 10-06-2010
Publisher: Informa UK Limited
Date: 03-2003
Abstract: The Pro/Pro polymorphism of p53 codon 72 has been reported to be related to bladder and lung cancer, but its relationship with skin cancer is unclear. We assessed the hypothesis that there is a relationship between the p53 codon 72, Pro/Pro polymorphism, cumulative arsenic exposure, and the risk of skin cancer in a hospital-based case-control study in southwestern Taiwan. From 1996 to 1999, 93 newly-diagnosed skin cancer patients at the National Cheng-Kung University (NCKU) Hospital and 71 community controls matched on residence were recruited in southwestern Taiwan. The genotype of p53 codon 72 (Arg/Arg, Arg/Pro, or Pro/Pro) was determined for all subjects by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP). A questionnaire was administered to each subject for collection of demographic information, personal habits, disease history, diet information, and other relevant questions. The Pro/Pro (homozygous) genotype was more frequent in skin cancer patients (cases, 20% controls, 12% P = 0.37). Subjects with the susceptible genotype Pro/Pro and heterozygous (intermediate) genotype Pro/Arg had 2.18 and 0.99 times risk of skin cancer than the wild type Arg/Arg (95% confidence interval, 0.74-4.38 95% confidence interval, 0.44-2.21), respectively. Compared with subjects with 18.5 < BMI 18.5 had 5.78 times risk of skin cancer (95% confidence interval, 1.06 to 31.36) after adjusting for other risk factors. There was no interaction between BMI and genotype, but the s le size was small. The risk of skin cancer did not significantly vary by tumor cell-type. The risk of skin cancer is increased in in iduals with the Pro/Pro genotype. Larger, confirmatory studies are needed to clarify the role of constitutional polymorphisms in p53 and skin cancer risk.
Publisher: Wiley
Date: 27-08-2004
Publisher: Wiley
Date: 04-2000
DOI: 10.1002/(SICI)1096-9926(200004)61:4<277::AID-TERA6>3.0.CO;2-W
Publisher: Wiley
Date: 26-08-2021
DOI: 10.1111/ACER.14686
Abstract: Cognitive and behavioral sequelae of prenatal alcohol exposure (PAE) continue to be prevalent in the United States and worldwide. Because these sequelae are also common in other neurodevelopmental disorders, researchers have attempted to identify a distinct neurobehavioral profile to facilitate the differential diagnosis of fetal alcohol spectrum disorders (FASD). We used an innovative, in idual participant meta‐analytic technique to combine data from six large U.S. longitudinal cohorts to provide a more comprehensive and reliable characterization of the neurobehavioral deficits seen in FASD than can be obtained from smaller s les. Meta‐analyses were performed on data from 2236 participants to examine effects of PAE (measured as oz absolute alcohol/day (AA/day)) on IQ, four domains of cognition function (learning and memory, executive function, reading achievement, and math achievement), sustained attention, and behavior problems, after adjusting for potential confounders using propensity scores. The effect sizes for IQ and the four domains of cognitive function were strikingly similar to one another and did not differ at school age, adolescence, or young adulthood. Effect sizes were smaller in the more middle‐class Seattle cohort and larger in the three cohorts that obtained more detailed and comprehensive assessments of AA/day. PAE effect sizes were somewhat weaker for parent‐ and teacher‐reported behavior problems and not significant for sustained attention. In a meta‐analysis of five aspects of executive function, the strongest effect was on set‐shifting. The similarity in the effect sizes for the four domains of cognitive function suggests that PAE affects an underlying component or components of cognition involving learning and memory and executive function that are reflected in IQ and academic achievement scores. The weaker effects in the more middle‐class cohort may reflect a more cognitively stimulating environment, a different maternal drinking pattern (lower alcohol dose/occasion), and/or better maternal prenatal nutrition. These findings identify two domains of cognition—learning/memory and set‐shifting—that are particularly affected by PAE, and one, sustained attention, which is apparently spared.
Publisher: Wiley
Date: 09-1992
DOI: 10.1111/J.1539-6924.1992.TB00696.X
Abstract: This paper reviews and compares several approaches to fitting dose-response models to developmental toxicity data. The main issue of interest is how to appropriately account for litter effects. Among the approaches reviewed are Beta Binomial models, models that attempt to characterize the litter effect through the use of covariates, and models that avoid the complication of correlated offspring by modeling "affected litter" rather than fetus-specific outcomes. Finally, we discuss our recommended approach, which is to use Generalized Estimating Equations, or quasi-likelihood. We give a number of reasons for preferring the latter and illustrate its application with an ex le.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2004
Publisher: Oxford University Press (OUP)
Date: 15-05-2004
DOI: 10.1093/AJE/KWH128
Abstract: Results of studies on paternal smoking and spontaneous abortions have been inconsistent. The authors examined the effect of paternal smoking on the risk of pregnancy loss in a prospective cohort of 526 newly married, nonsmoking, female textile workers in China between 1996 and 1998. Upon stopping contraception, subjects provided daily urine specimens and records of vaginal bleeding for up to 1 year or until clinical pregnancy. Daily urinary human chorionic gonadotropin was assayed to detect conception and early pregnancy losses, and pregnancies were followed to detect clinical spontaneous abortions. Subjects were grouped by the number of cigarettes that husbands reported smoking daily: nonsmokers (group 1, n = 216), fewer than 20 cigarettes (group 2, n = 239), and 20 or more cigarettes (group 3, n = 71). Compared with that for group 1, the adjusted odds ratio of early pregnancy loss of any conception for group 2 was 1.04 (95% confidence interval (CI): 0.67, 1.63) and for group 3 was 1.81 (95% CI: 1.00, 3.29). The adjusted hazard ratio of conception for group 2 was 0.90 (95% CI: 0.70, 1.18) and for group 3 was 0.96 (95% CI: 0.66, 1.39), while the adjusted hazard ratio of clinical pregnancy for group 2 was 0.93 (95% CI: 0.72, 1.20) and for group 3 was 0.78 (95% CI: 0.55, 1.12). The authors conclude that heavy paternal smoking increased the risk of early pregnancy loss through maternal and/or paternal exposure.
Publisher: Wiley
Date: 12-2000
DOI: 10.1111/J.0006-341X.2000.01139.X
Abstract: We propose a semiparametric approach to the proportional hazards regression analysis of interval-censored data. An EM algorithm based on an approximate likelihood leads to an M-step that involves maximizing a standard Cox partial likelihood to estimate regression coefficients and then using the Breslow estimator for the unknown baseline hazards. The E-step takes a particularly simple form because all incomplete data appear as linear terms in the complete-data log likelihood. The algorithm of Turnbull (1976, Journal of the Royal Statistical Society, Series B 38, 290-295) is used to determine times at which the hazard can take positive mass. We found multiple imputation to yield an easily computed variance estimate that appears to be more reliable than asymptotic methods with small to moderately sized data sets. In the right-censored survival setting, the approach reduces to the standard Cox proportional hazards analysis, while the algorithm reduces to the one suggested by Clayton and Cuzick (1985, Applied Statistics 34, 148-156). The method is illustrated on data from the breast cancer cosmetics trial, previously analyzed by Finkelstein (1986, Biometrics 42, 845-854) and several subsequent authors.
Publisher: Elsevier BV
Date: 12-1997
Publisher: Environmental Health Perspectives
Date: 12-2004
DOI: 10.1289/EHP.7234
Abstract: Most of the general population is exposed to carbaryl and other contemporary-use insecticides at low levels. Studies of laboratory animals, in addition to limited human data, show an association between carbaryl exposure and decreased semen quality. In the present study we explored whether environmental exposures to 1-naphthol (1N), a metabolite of carbaryl and naphthalene, and 3,5,6-trichloro-2-pyridinol (TCPY), a metabolite of chlorpyrifos and chlorpyrifos-methyl, are associated with decreased semen quality in humans. Subjects (n=272) were recruited through a Massachusetts infertility clinic. In idual exposures were measured as spot urinary concentrations of 1N and TCPY adjusted using specific gravity. Semen quality was assessed as sperm concentration, percent motile sperm, and percent sperm with normal morphology, along with sperm motion parameters (straight-line velocity, curvilinear velocity, and linearity). Median TCPY and 1N concentrations were 3.22 and 3.19microg/L, respectively. For increasing 1N tertiles, adjusted odds ratios (ORs) were significantly elevated for below-reference sperm concentration (OR for low, medium, and high tertiles = 1.0, 4.2, 4.2, respectively p-value for trend =0.01) and percent motile sperm (1.0, 2.5, 2.4 p-value for trend = 0.01). The sperm motion parameter most strongly associated with 1N was straight-line velocity. There were suggestive, borderline-significant associations for TCPY with sperm concentration and motility, whereas sperm morphology was weakly and nonsignificantly associated with both TCPY and 1N. The observed associations between altered semen quality and 1N are consistent with previous studies of carbaryl exposure, although suggestive associations with TCPY are difficult to interpret because human and animal data are currently limited.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 1988
Abstract: All mesothelioma patients identified by a computer search of pathologic diagnoses at the Dana-Farber Cancer Institute (DFCI) between 1965 and 1985 were the subjects of this analysis. A total of 180 patients were identified, 136 with pleural and 37 with peritoneal mesothelioma. There were five pericardial and two testicular primaries. Of the two decades included in the study, later patients were significantly older, with a more advanced disease stage, and a lower performance status than those accrued early in the study. Factors at diagnosis associated with a significantly prolonged survival for all patients with mesothelioma included a 0 to 1 performance status, absence of chest pain, age less than 50 years, and epithelial histology. Factors at diagnosis associated with prolonged survival for the subset of patients with pleural mesothelioma included epithelial histology, 0 to 1 performance status, the absence of chest pain, an interval of greater than 6 months from onset of symptoms, and treatment with chemotherapy and pleuropneumonectomy. This last result must be interpreted with caution, since this was not a randomized study.
Publisher: Wiley
Date: 15-04-1999
DOI: 10.1002/(SICI)1097-0258(19990415)18:7<890::AID-SIM90>3.0.CO;2-7
Publisher: Informa UK Limited
Date: 03-05-2021
DOI: 10.1080/13557858.2019.1613518
Abstract: This study aimed to understand the experiences of bilingual nurses asked to interpret in the Emergency Department (ED), and the subsequent impact on safety climate. Australian ED clinicians assess and treat high numbers of linguistically erse patients, many with limited English proficiency. New South Wales Health policy mandates the use of accredited interpreters when collecting personal and health information, and when obtaining consent for medical procedures. Semi-structured interviews with 12 nurses (representing 12 languages) from two metropolitan EDs were audio-recorded and analysed using qualitative content analysis, guided by Glendon & Stanton's model of organisational climate and culture. Analysis revealed widespread underlying assumptions that engaging interpreters is difficult, time-consuming and costly. Bilingual ED nurses with variable language fluency were used across organisations as the first choice due to clinical urgency, task urgency, and hospital workflow pressures. While the use of nurse interpreters facilitated timely assessment for the benefit of patients, it equally led to increased nurse workload, missed or misinterpreted information and subsequent perceived clinical risk. These practices were supported and facilitated by unit level managerial and multidisciplinary team practices, physician pressure and the nurses' own values and beliefs. While some, (but not all) participants were aware of the interpreter policy, they were torn between their acknowledgement of risky translation practices and their desire to support their colleagues to provide timely, culturally-competent assessment and care. Findings suggests a 'top-down' approach to translation policy has failed to influence the local safety culture and practices and does not address a climate created by clinical urgency and workflow. Formal training and accreditation of bilingual nurses, and/or embedded interpreters for common language groups may reduce risks for non-English speaking patients.
Publisher: Wiley
Date: 30-01-1998
DOI: 10.1002/(SICI)1097-0258(19980130)17:2<219::AID-SIM735>3.0.CO;2-O
Abstract: In standard time-to-event or survival analysis, occurrence times of the event of interest are observed exactly or are right-censored, meaning that it is only known that the event occurred after the last observation time. There are numerous methods available for estimating the survival curve and for testing and estimation of the effects of covariates in this context. In some situations, however, the times of the events of interest may only be known to have occurred within an interval of time. In clinical trials, for ex le, patients are often seen at pre-scheduled visits but the event of interest may occur in between visits. These data are interval-censored. Owing to the lack of well-known statistical methodology and available software, a common ad hoc approach is to assume that the event occurred at the end (or beginning or midpoint) of each interval, and then apply methods for standard time-to-event data. However, this approach can lead to invalid inferences, and in particular will tend to underestimate the standard errors of the estimated parameters. The purpose of this tutorial is to illustrate and compare available methods which correctly treat the data as being interval-censored. It is not meant to be a full review of all existing methods, but only those which are available in standard statistical software, or which can be easily programmed. All approaches will be illustrated on two data sets and compared with methods which ignore the interval-censored nature of the data. We hope this tutorial will allow those familiar with the application of standard survival analysis techniques the option of applying appropriate methods when presented with interval-censored data.
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.CANEP.2015.03.001
Abstract: Preventing risk factor exposure is vital to reduce the high burden from lung cancer. The leading risk factor for developing lung cancer is tobacco smoking. In Australia, despite apparent success in reducing smoking prevalence, there is limited information on small area patterns and small area temporal trends. We sought to estimate spatio-temporal patterns for lung cancer risk factors using routinely collected population-based cancer data. The analysis used a Bayesian shared component spatio-temporal model, with male and female lung cancer included separately. The shared component reflected lung cancer risk factors, and was modelled over 477 statistical local areas (SLAs) and 15 years in Queensland, Australia. Analyses were also run adjusting for area-level socioeconomic disadvantage, Indigenous population composition, or remoteness. Strong spatial patterns were observed in the underlying risk factor estimates for both males (median Relative Risk (RR) across SLAs compared to the Queensland average ranged from 0.48 to 2.00) and females (median RR range across SLAs 0.53-1.80), with high risks observed in many remote areas. Strong temporal trends were also observed. Males showed a decrease in the underlying risk across time, while females showed an increase followed by a decrease in the final 2 years. These patterns were largely consistent across each SLA. The high underlying risk estimates observed among disadvantaged, remote and indigenous areas decreased after adjustment, particularly among females. The modelled underlying risks appeared to reflect previous smoking prevalence, with a lag period of around 30 years, consistent with the time taken to develop lung cancer. The consistent temporal trends in lung cancer risk factors across small areas support the hypothesis that past interventions have been equally effective across the state. However, this also means that spatial inequalities have remained unaddressed, highlighting the potential for future interventions, particularly among remote areas.
Publisher: Springer Science and Business Media LLC
Date: 12-2007
DOI: 10.1007/S10985-007-9068-7
Abstract: In large epidemiological studies, budgetary or logistical constraints will typically preclude study investigators from measuring all exposures, covariates and outcomes of interest on all study subjects. We develop a flexible theoretical framework that incorporates a number of familiar designs such as case control and cohort studies, as well as multistage s ling designs. Our framework also allows for designed missingness and includes the option for outcome dependent designs. Our formulation is based on maximum likelihood and generalizes well known results for inference with missing data to the multistage setting. A variety of techniques are applied to streamline the computation of the Hessian matrix for these designs, facilitating the development of an efficient software tool to implement a wide variety of designs.
Publisher: Informa UK Limited
Date: 1997
Publisher: Wiley
Date: 09-2019
Abstract: The advent of the big data age has changed the landscape for statisticians. Public and private organizations alike these days are interested in capturing and analyzing complex customer data in order to improve their service and drive efficiency gains. However, the large volume of data involved often means that standard statistical methods fail and new ways of thinking are needed. Although great gains can be obtained through the use of more advanced computing environments or through developing sophisticated new statistical algorithms that handle data in a more efficient way, there are also many simpler things that can be done to handle large data sets in an efficient and intuitive manner. These include the use of distributed analysis methodologies, clever subs ling, data coarsening, and clever data reductions that exploit concepts such as sufficiency. These kinds of strategies represent exciting opportunities for statisticians to remain front and center in the data science world.
Publisher: Environmental Health Perspectives
Date: 04-2009
DOI: 10.1289/EHP.11846
Publisher: Elsevier BV
Date: 02-2012
DOI: 10.1016/J.NEUROIMAGE.2011.10.014
Abstract: The hippoc us is affected at an early stage in the development of Alzheimer's disease (AD). With the use of structural magnetic resonance (MR) imaging, we can investigate the effect of AD on the morphology of the hippoc us. The hippoc al shape variations among a population can be usually described using statistical shape models (SSMs). Conventional SSMs model the modes of variations among the population via principal component analysis (PCA). Although these modes are representative of variations within the training data, they are not necessarily discriminative on labeled data or relevant to the differences between the subpopulations. We use the shape descriptors from SSM as features to classify AD from normal control (NC) cases. In this study, a Hotelling's T2 test is performed to select a subset of landmarks which are used in PCA. The resulting variation modes are used as predictors of AD from NC. The discrimination ability of these predictors is evaluated in terms of their classification performances with bagged support vector machines (SVMs). Restricting the model to landmarks with better separation between AD and NC increases the discrimination power of SSM. The predictors extracted on the subregions also showed stronger correlation with the memory-related measurements such as Logical Memory, Auditory Verbal Learning Test (AVLT) and the memory subscores of Alzheimer Disease Assessment Scale (ADAS).
Publisher: Informa UK Limited
Date: 2009
Publisher: Wiley
Date: 10-2008
DOI: 10.1002/JTS.20362
Publisher: Wiley
Date: 09-08-2018
DOI: 10.1002/SIM.7693
Publisher: Wiley
Date: 15-04-2003
DOI: 10.1002/CNCR.11290
Abstract: The current study was conducted to evaluate the antitumor activity and toxicity of gemcitabine in patients with advanced sarcoma. Twenty-five patients with advanced sarcomas, who previously were untreated for metastatic disease, were treated on an Eastern Cooperative Oncology Group Phase II study. Patients ranged in age from 27 to 79 years, with a median age of 59 years. The most common histology was leiomyosarcoma (54%). The grades of the tumors were high in 40%, moderate in 24% and low in 12%. Gemcitabine was given at a dose of 1250 mg/m(2) as a 30-minute infusion weekly for 3 weeks followed by 1 week of rest. One of the 25 patients (4%) (90% confidence interval [90% CI], 0-18%) achieved a partial response lasting 8 months. The estimated overall median survival was 15 months. The 1-year estimated survival rate was 63% (90% CI, 47-84%). The estimated median progression-free survival (PFS) was 13 months with a 1-year PFS rate of 56% (90% CI, 41-76%). Grade 3-4 toxicities (by CTC criteria) were observed in all 25 patients. No lethal toxicity (Grade 5) related to treatment was found. The results of the current study demonstrated that gemcitabine given at this schedule and dose in this population of patients with advanced sarcoma had limited activity.
Publisher: Institute of Mathematical Statistics
Date: 06-2009
DOI: 10.1214/08-AOAS226
Publisher: Wiley
Date: 06-2010
DOI: 10.1002/SIM.3892
Publisher: American Medical Association (AMA)
Date: 03-1998
DOI: 10.1001/ARCHOPHT.116.3.366
Abstract: To evaluate whether the removal of the eye after radiotherapy alters the rates of metastatic death in patients with melanoma of the choroid. Using an extension of the Cox model, we based our analysis on a cohort of 1541 consecutive patients with unilateral choroidal or ciliary body melanoma treated with protons (70 cobalt-gray equivalent in 5 to 7 fractions) at the Harvard University (Boston, Mass) cyclotron between July 1, 1975, through December 31, 1993, and who were observed prospectively up to September 30, 1995. Patient survival and the status of the treated eye were updated annually. By September 1995 (median follow-up among survivors, 8 years), 137 patients underwent enucleation after radiotherapy for complications (n=103) or tumor regrowth (n=34). The overall 10-year rate of eye retention was 89% (95% confidence interval, 87%-91%). Of the 1541 patients, 300 died of tumor metastasis, 38 following enucleation of the affected eye (mean interval from enucleation to death, 25 months). The multivariate rate ratio for metastatic death associated with enucleation (modeled as a time-dependent covariate) was 0.9 (95% confidence interval, 0.6-1.4) for enucleation due to complications and 3.8 (95% confidence interval, 2.3-6.3) for enucleation associated with tumor regrowth. In the absence of tumor viability, enucleation after primary irradiation for choroidal melanoma has no deleterious effect on patients' survival. Enucleation concurrent with tumor regrowth is associated with high death rates growth of the tumor in the eye may presage systemic recurrence and death from metastasis.
Publisher: Environmental Health Perspectives
Date: 03-2002
DOI: 10.1289/EHP.02110229
Abstract: There have been numerous studies that suggest that sperm concentrations (sperm counts) are declining in men. However, other studies suggest that sperm counts are not declining or may be increasing in some areas. Although there is disagreement on whether there is a downward temporal trend in sperm counts, the studies provide evidence that sperm counts vary by geographic location. It has been hypothesized that the geographic variation in sperm concentrations may be due to environmental exposures, lifestyle factors, or some unknown causes. To determine whether contemporary ambient levels of polychlorinated biphenyls (PCBs) and p,p-DDE are associated with altered semen quantity and quality, we selected a study population without specific exposure to PCBs or p,p-DDE. The present study presents the results from a pilot study on the relationship between serum PCBs and p,p-DDE and semen quality in 29 subjects recruited from the Massachusetts General Hospital Andrology Laboratory. Of the 29 subjects, 3 had sperm concentrations < 20 million/mL, 7 had < 50% motile sperm, 9 had < 4% normal morphology, and 6 were below normal in more than one semen parameter. The 18 subjects with normal spermatozoa concentration, motility, and morphology were used as comparison subjects. The mean (SE) concentration of the sum of PCBs and p,p-DDE was 242 ng/g lipids (34.0) and 354 ng/g lipids (120), respectively, for men with below normal motility as compared to 202 ng/g lipids (16.6) and 240 ng/g lipids (31.1), respectively, for the comparison subjects. The data showed general trends that were suggestive of an association between PCBs and p,p-DDE and abnormal motility, as well as with sperm concentration and morphology. A full-scale study is currently in progress.
Publisher: Oxford University Press (OUP)
Date: 04-2002
Abstract: To examine the reliability of HCG as a biomarker for early pregnancy loss, five experienced researchers independently assessed data from 153 menstrual cycles, determining whether each cycle represented 'no conception,' a 'continuing conception' or a 'conception lost.' Urine s les were analysed by immunoradiometric assay using a combination of capture antibodies for the intact heterodimer (B109) and for an epitope common to the beta subunit and the beta core fragment (B204). For each cycle, HCG data were presented as graphs of daily assay results. Summary statistics for HCG assays from 46 women who had undergone bilateral tubal ligation represented baseline values. Pairwise agreement among the assessors for any of the three options ranged from 78-89%. At least three experts agreed for 147 cycles (96%), accounting for 28 conception losses and 19 continuing conceptions. The multi-rater kappa was 0.62 for the conception lost category and 0.68 for continuing conceptions, indicating substantial agreement. The main sources of disagreement involved deciding whether there was sufficient information for assessment, interpreting cycle parameters such as cycle length or bleeding event, and interpreting a distinct HCG rise pattern that does not exceed the baseline value obtained from the sterilized women.
Publisher: Environmental Health Perspectives
Date: 07-2000
DOI: 10.1289/EHP.00108655
Abstract: The U.S. Environmental Protection Agency is under a congressional mandate to revise its current standard for arsenic in drinking water. We present a risk assessment for cancers of the bladder, liver, and lung from exposure to arsenic in water, based on data from 42 villages in an arseniasis-endemic region of Taiwan. We calculate excess lifetime risk estimates for several variations of the generalized linear model and for the multistage-Weibull model. Risk estimates are sensitive to the model choice, to whether or not a comparison population is used to define the unexposed disease mortality rates, and to whether the comparison population is all of Taiwan or just the southwestern region. Some factors that may affect risk could not be evaluated quantitatively: the ecologic nature of the data, the nutritional status of the study population, and the dietary intake of arsenic. Despite all of these sources of uncertainty, however, our analysis suggests that the current standard of 50 microg/L is associated with a substantial increased risk of cancer and is not sufficiently protective of public health.
Publisher: Oxford University Press (OUP)
Date: 21-11-2022
Abstract: To celebrate the 60th anniversary of the Statistical Society of Australia, we put the spotlight on four members past and present. Interviews and profiles by Louise Ryan, John Henstridge and Jessica Kasza
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2011
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2008
Publisher: Springer Science and Business Media LLC
Date: 09-2004
Publisher: Elsevier BV
Date: 09-1998
DOI: 10.1016/S0022-3476(98)70267-7
Abstract: To examine the efficacy of a combination of 4 blood markers of alcohol use in detecting alcohol-abusing pregnant women. Two new markers of alcohol use, whole blood-associated acetaldehyde and carbohydrate-deficient transferrin, and 2 traditional markers of alcohol use, gamma-glutamyl transpeptidase and mean red blood cell volume, were measured in the blood of pregnant women. Each woman was interviewed about alcohol and drug use, medical and obstetric histories, and nutrition. Each infant was examined by a clinician who was blinded to exposure status. All of the women who reported drinking an average of 1 or more ounces of absolute alcohol per day had at least 1 positive blood marker. The infants of mothers with 2 or more positive markers had significantly smaller birth weights, lengths, and head circumferences than the infants with negative maternal screens. The presence of 2 or more positive markers was more predictive of infant outcome than any self-reporting measure. These markers, which detect more at-risk pregnant women than self-reporting methods, could lead to better efforts at detection and prevention of alcohol-induced fetal damage.
Publisher: American Academy of Pediatrics (AAP)
Date: 11-2008
Abstract: OBJECTIVE. The goal was to determine whether cumulative exposure to violence in childhood and adolescence contributes to disparities in self-rated health among a nationally representative s le of US adolescents. METHODS. The National Longitudinal Survey of Youth 1997 is an ongoing, 8-year (1997–2004), longitudinal, cohort study of youths who were 12 to 18 years of age at baseline (N = 8224). Generalized estimating equations were constructed to investigate the relationship between cumulative exposure to violence and risk for poor health. RESULTS. At baseline, 75% of subjects reported excellent or very good health, 21.5% reported good health, and 4.5% reported fair or poor health. Cumulative violence exposures (witnessed gun violence, threat of violence, repeated bullying, perceived safety, and criminal victimization) were associated with a graded increase in risk for poor health and reduced the strength of the relationship between household income and poor health. In comparison with subjects with no violence exposure, risk for poor self-rated health was 4.6 times greater among subjects who reported ≥5 forms of cumulative exposure to violence, controlling for demographic features and household income. Trend analysis revealed that, for each additional violence exposure, the risk of poor health increased by 38%. Adjustment for alcohol use, drug use, smoking, depressive symptoms, and family and neighborhood environment reduced the strength of the relationships between household income and cumulative exposure to violence scores and poor self-rated health, which suggests partial mediation of the effects of socioeconomic status and cumulative exposure to violence by these factors. CONCLUSIONS. In this nationally representative s le, social inequality in risk for poor self-rated health during the transition from adolescence to adulthood was partially attributable to disparities in cumulative exposure to violence. A strong graded association was noted between cumulative exposure to violence and poor self-rated health in adolescence and young adulthood.
Publisher: JSTOR
Date: 1985
DOI: 10.2307/2347885
Publisher: Springer Science and Business Media LLC
Date: 14-07-2009
Publisher: Informa UK Limited
Date: 09-2003
Publisher: JSTOR
Date: 06-1996
DOI: 10.2307/2532903
Publisher: Institute of Mathematical Statistics
Date: 11-2003
Publisher: Environmental Health Perspectives
Date: 1994
DOI: 10.1289/EHP.94102S19
Abstract: The three-state illness-death model provides a useful way to characterize data from a rodent tumorigenicity experiment. Most parametrizations proposed recently in the literature assume discrete time for the death process and either discrete or continuous time for the tumor onset process. We compare these approaches with a third alternative that uses a piecewise continuous model on the hazards for tumor onset and death. All three models assume proportional hazards to characterize tumor lethality and the effect of dose on tumor onset and death rate. All of the models can easily be fitted using an Expectation Maximization (EM) algorithm. The piecewise continuous model is particularly appealing in this context because the complete data likelihood corresponds to a standard piecewise exponential model with tumor presence as a time-varying covariate. It can be shown analytically that differences between the parameter estimates given by each model are explained by varying assumptions about when tumor onsets, deaths, and sacrifices occur within intervals. The mixed-time model is seen to be an extension of the grouped data proportional hazards model [Mutat. Res. 24:267-278 (1981)]. We argue that the continuous-time model is preferable to the discrete- and mixed-time models because it gives reasonable estimates with relatively few intervals while still making full use of the available information. Data from the ED01 experiment illustrate the results.
Publisher: Oxford University Press (OUP)
Date: 03-2005
Abstract: Phthalates are used in personal and consumer products, food packaging materials, and polyvinyl chloride plastics and have been measured in the majority of the general population of the USA. Consistent experimental evidence shows that some phthalates are developmental and reproductive toxicants in animals. This study explored the association between environmental levels of phthalates and altered reproductive hormone levels in adult men. Between 1999 and 2003, 295 men were recruited from Massachusetts General Hospital. Selected phthalate metabolites were measured in urine. Linear regression models explored the relationship between specific gravity-adjusted urinary phthalate monoester concentrations and serum levels of reproductive hormones, including FSH, LH, sex hormone-binding globulin, testosterone, and inhibin B. An interquartile range (IQR) change in monobenzyl phthalate (MBzP) exposure was significantly associated with a 10% [95% confidence interval (CI): -16, -4.0] decrease in FSH concentration. Additionally, an IQR change in monobutyl phthalate (MBP) exposure was associated with a 4.8% (95% CI: 0, 10) increase in inhibin B but this was of borderline significance. Although we found associations between MBP and MBzP urinary concentrations and altered levels of inhibin B and FSH, the hormone concentrations did not change in the expected patterns. Therefore, it is unclear whether these associations represent physiologically relevant alterations in these hormones, or whether they represent associations found as a result of conducting multiple comparisons.
Publisher: Oxford University Press (OUP)
Date: 1995
Publisher: American Public Health Association
Date: 04-2004
Abstract: Objectives. We explored a postulated association between daily driving time and knee pain. Methods. We used data from the Taxi Drivers’ Health Study to estimate 1-year prevalence of knee pain as assessed by the Nordic musculoskeletal questionnaire. Results. Among 1242 drivers, the prevalence of knee pain, stratified by duration of daily driving (≤ 6, 6 through 8, 8 through 10, and 10 hours), was 11%, 17%, 19%, and 22%, respectively. Compared with driving 6 or fewer hours per day, the odds ratio of knee pain prevalence for driving more than 6 hours per day was 2.52 (95% confidence interval = 1.36, 4.65) after we adjusted for socioeconomic, work-related, and personal factors in the multiple logistic regression. Conclusions. The dose-related association between driving duration and knee pain raises concerns about work-related knee joint disorders among professional drivers.
Publisher: Oxford University Press (OUP)
Date: 19-11-2013
Publisher: Wiley
Date: 27-06-2005
DOI: 10.1002/ENV.713
Publisher: BMJ
Date: 10-2000
Abstract: The association between birth weight and exposure to benzene, work stress, and other occupational and environmental hazards was investigated. In a large petrochemical industry, 792 pregnant workers were enrolled and followed up through delivery between May 1996 and December 1998. Exposure to benzene and other solvents was assessed by an industrial hygienist based on each woman's job title and workplace information. Other occupational and environmental exposures and personal information, including perceived work stress, exposure to noise, physical exertion at work, and passive smoking, were obtained by an interview questionnaire. Univariate and multivariate regression models were used to examine the in idual and combined associations of occupational and environmental exposures with birth weight, with adjustment for major confounders including gestational age. In the univariate model, birth weight was negatively associated with exposure to benzene (-58 g (95% confidence interval (95% CI), -115 to -2)) and with work stress (-84 g (95% CI, -158 to -10)). In the multivariate model, there was a significant interaction between exposure to benzene and work stress relative to reduced birth weight, after adjustment for other environmental and occupational exposures and personal variables. Adjusted mean birth weight was 3445 g (95% CI 3401 to 3489) among those with neither exposure, 3430 g for those with exposure to benzene only, 3426 g for those with work stress only, and 3262 g (95% CI 3156 to 3369) for those with both exposures. In other words, there was 183 g (95% CI 65 to 301) reduction in birth weight among those with both exposure to benzene and work stress compared with those with neither exposure. Other work or environmental factors could not explain these findings. Low level exposure to benzene and work stress interact to reduce birth weight in this population.
Publisher: Oxford University Press (OUP)
Date: 08-1999
Abstract: In risk assessment, evaluating a health effect at a duration of exposure that is untested involves assuming that equivalent multiples of concentration (C) and duration (T) of exposure have the same effect. The limitations of this approach (attributed to F. Haber, Zur Geschichte des Gaskrieges [On the history of gas warfare], in Funf Vortrage aus den Jahren 1920-1923 [Five lectures from the years 1920-1923], 1924, Springer, Berlin, pp. 76-92), have been noted in several studies. The study presented in this paper was designed to specifically look at dose-rate (C x T) effects, and it forms an ideal case study to implement statistical models and to examine the statistical issues in risk assessment. Pregnant female C57BL/6J mice were exposed, on gestational day 7, to ethylene oxide (EtO) via inhalation for 1.5, 3, or 6 h at exposures that result in C x T multiples of 2100 or 2700 ppm-h. EtO was selected because of its short half-life, documented developmental toxicity, and relevance to exposures that occur in occupational settings. Concurrent experiments were run with animals exposed to air for similar periods. Statistical analysis using models developed to assess dose-rate effects revealed significant effects with respect to fetal death and resorptions, malformations, crown-to-rump length, and fetal weight. Animals exposed to short, high exposures of EtO on day 7 of gestation were found to have more adverse effects than animals exposed to the same C x T multiple but at longer, lower exposures. The implication for risk assessment is that applying Haber's Law could potentially lead to an underestimation of risk at a shorter duration of exposure and an overestimation of risk at a longer duration of exposure. Further research, toxicological and statistical, are required to understand the mechanism of the dose-rate effects, and how to incorporate the mechanistic information into the risk assessment decision process.
Publisher: Wiley
Date: 04-1993
Abstract: The purpose of this paper is to present a statistical model for analyzing the joint effects of exposure on fetal death, fetal weight, and malformation in a developmental toxicity study. In addition to allowing for the usual litter effect, the model allows for correlations between different outcomes measured on the same fetus. Fitting the model requires first focusing on non-live outcomes by modeling the probability of fetal death or resorption as a function of dose. Then outcomes among live fetuses are modeled using a two-stage regression approach. The first stage models fetal weight as a function of dose and the second stage models fetal malformation as a function of dose, as well as residuals from the weight model. The regression coefficients from the malformation model have intuitive interpretations in terms of correlations between littermates and between different outcomes measured within the same fetus. Not only does the approach provide a useful way to investigate the relationship between adverse fetal outcomes, it also yields a natural framework for conducting quantitative risk assessment. A procedure is proposed for quantifying overall risk by incorporating the three outcomes in order to estimate safe dose levels and corresponding lower confidence limits. The method is illustrated using data from an experiment in mice conducted through the National Toxicology Program.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2006
DOI: 10.1097/01.EDE.0000190602.14691.70
Abstract: Urinary metabolites of several nonpersistent insecticides have been measured in a high percentage of men in the general population, suggesting widespread environmental exposures to these compounds. The present study explored the association of urinary concentrations of 3,5,6-trichloro-2-pyridinol (TCPY), a metabolite of chlorpyrifos and chlorpyrifos-methyl, and 1-naphthol (1N), a metabolite of carbaryl and naphthalene, with serum reproductive hormone levels in adult men. Subjects (n = 268) were the male partners in couples presenting to a Massachusetts infertility clinic in years 2000 through 2003. TCPY and 1N were measured in a spot urine s le from each subject and adjusted for dilution using specific gravity. Reproductive hormones (follicle-stimulating hormone, leuteinizing hormone, inhibin B, testosterone, and sex hormone-binding globulin) were measured in serum collected from subjects during the same clinic visit. Multiple linear regression models showed an inverse association between TCPY and testosterone concentration. An interquartile range (IQR) increase in TCPY was associated with a decline of 25 ng/dL (95% confidence interval = -40 to -10) in testosterone concentration. The association appeared to be dose-dependent when exposure was ided into quintiles. The highest TCPY quintile was associated with a testosterone decline of 83 ng/dL (-128 to -39) compared with the lowest TCPY quintile. We also found inverse associations between TCPY and free androgen index and between 1N and testosterone, and suggestive inverse associations between TCPY and leuteinizing hormone and between 1N and free androgen index. In adult men, TCPY and 1N were associated with reduced testosterone levels. On a population level, these reductions are of potential public health importance because of widespread exposure to these nonpersistent insecticides.
Publisher: Wiley
Date: 11-12-2017
DOI: 10.1002/SIM.7543
Abstract: In many settings, an analysis goal is the identification of a factor, or set of factors associated with an event or outcome. Often, these associations are then used for inference and prediction. Unfortunately, in the big data era, the model building and exploration phases of analysis can be time-consuming, especially if constrained by computing power (ie, a typical corporate workstation). To speed up this model development, we propose a novel subs ling scheme to enable rapid model exploration of clustered binary data using flexible yet complex model set-ups (GLMMs with additive smoothing splines). By reframing the binary response prospective cohort study into a case-control-type design, and using our knowledge of s ling fractions, we show one can approximate the model estimates as would be calculated from a full cohort analysis. This idea is extended to derive cluster-specific s ling fractions and thereby incorporate cluster variation into an analysis. Importantly, we demonstrate that previously computationally prohibitive analyses can be conducted in a timely manner on a typical workstation. The approach is applied to analysing risk factors associated with adverse reactions relating to blood donation.
Publisher: Springer Science and Business Media LLC
Date: 2002
Publisher: Springer Science and Business Media LLC
Date: 12-2005
Publisher: Elsevier BV
Date: 10-2001
DOI: 10.1016/S1047-2797(01)00239-3
Abstract: Spontaneous abortion (SAB), the most common adverse pregnancy outcome, affects approximately 15% of clinically recognized pregnancies. Except for advanced maternal age and smoking, there are not well-established risk factors for SAB. Animal models associate increased fetal resorption or abortion with exposure to the pesticide dichlorodiphenyl trichloroethane (DDT), but epidemiologic investigations of DDT and SAB are inconsistent. We undertook a pilot investigation of the hypothesized association of DDT with SAB. Participants in this case-control study were selected from a longitudinal study of reproductive effects of rotating shifts among female Chinese textile workers who were married, ages 22-34, nulliparous without history of SAB or infertility, and planning pregnancy. From 412 pregnancies, 42 of which ended in SAB, 15 SAB cases and 15 full-term controls were randomly selected and phlebotomized. Serum was analyzed for p,p'-DDT, o,p'-DDT, their metabolites (DDE and DDD), and other organochlorines including polychlorinated biphenyls. Cases and controls were nonsmokers and did not differ in age (mean 25 years), body mass index (BMI), passive smoke exposure, or workplace exposures. Cases had significantly (p < 0.05) higher serum levels of p,p'-DDE (22 vs.12 ng/g) and o,p'-DDE (0.09 vs. 0.05 ng/g) than controls. After adjustment for age and BMI, each ng/g serum increase in p,p'-DDE was associated with a 1.13 (CI, 1.02-1.26) increased odds of SAB. With adjustment of serum DDE levels for excretion via breastfeeding, DDE-associated increased odds of SAB remained significant with up to 7% declines in maternal serum DDE levels for each month of breastfeeding. A potential increased risk of SAB is associated with maternal serum DDE levels.
Publisher: Oxford University Press (OUP)
Date: 1989
Publisher: American Academy of Pediatrics (AAP)
Date: 12-2002
Abstract: Objective. Bottle feeding in the bed or crib before sleep time has been associated with an increased risk of wheezing in the first year of life. We examined whether bottle feeding in the bed or crib before sleep time in the first year of life is associated with wheezing in the first 5 years of life. Methods. In a prospective cohort study of 448 children with parental history of atopy followed from birth, we examined the relation between the number of bimonthly parental reports of bottle feeding in the bed or crib before sleep time in the first year of life (range: 0–6 reports) and parental report of wheezing in the first 5 years of life. Additional outcome measures included recurrent wheezing (≥2 episodes of wheezing in the previous year) and asthma (physician-diagnosed asthma and ≥1 episode of wheezing in the previous year) at the age of 5 years. Results. The risk of recurrent wheezing and asthma at 5 years of age increased significantly with each additional report of bottle feeding in the bed or crib before sleep time in the first year of life. The risk of wheezing between the ages of 1 and 5 years increased with each additional report of bottle feeding in the bed or crib before sleep time in the first year of life. As an ex le, a child whose parents reported bottle feeding in the bed or crib before sleep time on 3 occasions in the first year of life had 1.5 times higher risk of wheezing between the ages of 1 and 5 years than a child whose parents did not report bottle feeding in the bed or crib before sleep time in the first year of life (95% confidence interval for relative risk: 1.12–2.12). Conclusions. Among children with parental history of atopy, bottle feeding in the bed or crib before sleep time in the first year of life is a risk factor for recurrent wheezing and asthma at 5 years of age and a risk factor for wheezing between the ages of 1 and 5 years.
Publisher: Wiley
Date: 12-1993
Publisher: Environmental Health Perspectives
Date: 04-2007
DOI: 10.1289/EHP.9303
Publisher: Elsevier BV
Date: 08-2005
DOI: 10.1016/J.JACI.2005.05.015
Abstract: Infant endotoxin exposure has been proposed as a factor that might protect against allergy and the early childhood immune responses that increase the risk of IgE production to allergens. Using a prospective study design, we tested the hypothesis that early-life endotoxin exposure is associated with allergen- and mitogen-induced cytokine production and proliferative responses of PBMCs isolated from infants with a parental history of physician-diagnosed asthma or allergy. We assessed household dust endotoxin at age 2 to 3 months and PBMC proliferative and cytokine responses to cockroach allergen (Bla g 2), dust mite allergen (Der f 1), cat allergen (Fel d 1), and the nonspecific mitogen PHA at age 2 to 3 years. We found that increased endotoxin levels were associated with decreased IL-13 levels in response to cockroach, dust mite, and cat allergens, but not mitogen stimulation. Endotoxin levels were not correlated with allergen- or mitogen-induced IFN-gamma, TNF-alpha, or IL-10. Increased endotoxin levels were associated with decreased lymphocyte proliferation after cockroach allergen stimulation. An inverse, although nonsignificant, association was also found between endotoxin and proliferation to the other tested stimuli. Increased early-life exposure to household endotoxin was associated with reduced allergen-induced production of the TH2 cytokine IL-13 and reduced lymphoproliferative responses at age 2 to 3 years in children at risk for allergy and asthma. Early-life endotoxin-related reduction of IL-13 production might represent one pathway through which increased endotoxin decreases the risk of allergic disease and allergy in later childhood.
Publisher: Wiley
Date: 06-2002
DOI: 10.1111/J.0006-341X.2002.00287.X
Abstract: We propose a new class of semiparametric frailty models for spatially correlated survival data. Specifically, we extend the ordinary frailty models by allowing random effects accommodating spatial correlations to enter into the baseline hazard function multiplicatively. We prove identifiability of the models and give sufficient regularity conditions. We propose drawing inference based on a marginal rank likelihood. No parametric forms of the baseline hazard need to be assumed in this semiparametric approach. Monte Carlo simulations and the Laplace approach are used to tackle the intractable integral in the likelihood function. Different spatial covariance structures are explored in simulations and the proposed methods are applied to the East Boston Asthma Study to detect prognostic factors leading to childhood asthma.
Publisher: Elsevier BV
Date: 05-1997
Publisher: American Medical Association (AMA)
Date: 06-2015
DOI: 10.1001/JAMADERMATOL.2014.3593
Abstract: The total cost of psoriasis in the United States is unknown. Defining the US economic burden of psoriasis is needed because it provides the foundation for research, advocacy, and educational efforts. To determine the US economic burden of psoriasis from a societal perspective. PubMed and MEDLINE databases were searched between January 1, 2008, and September 20, 2013, for economic investigations on the direct, indirect, intangible, and comorbidity costs of adult psoriasis in the United States. The base year costs were adjusted to 2013 US dollars using the Consumer Price Index for All Urban Consumers and multiplied by the estimated number of US patients with psoriasis in 2013 to determine the 2013 psoriasis cost burden. Among 100 identified articles, 22 studies were included in the systematic review. The direct psoriasis costs ranged from $51.7 billion to $63.2 billion, the indirect costs ranged from $23.9 billion to $35.4 billion, and medical comorbidities were estimated to contribute $36.4 billion annually in 2013 US dollars. Patients with psoriasis would pay a lifetime cost of $11,498 for relief of physical symptoms and emotional health however, intangible cost data are limited. The annual US cost of psoriasis amounted to approximately $112 billion in 2013. The economic burden of psoriasis is substantial and significant in the United States.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-1991
DOI: 10.1097/00000421-199102000-00007
Abstract: Twenty-three patients with advanced inoperable squamous cell carcinoma of the esophagus were treated with aminothiadiazole (A-TD) 125 mg/m2 weekly plus allopurinol daily in a phase II cooperative group trial. No patients responded to treatment 17 patients progressed, three showed stable disease, and three were unevaluable. There were no life-threatening hematologic or metabolic toxicities. The median survival from study entry was 5 months. A-TD is not active in advanced squamous cell carcinoma of the esophagus.
Publisher: Elsevier BV
Date: 10-1998
Abstract: Safety assessment for noncancer health effects generally has been based upon iding a no observed adverse effect (NOAEL) by uncertainty (safety) factors to provide an acceptable daily intake (ADI) or reference dose (RfD). Since the NOAEL does not utilize all of the available dose-response data, allows higher ADI from poorer experiments, and may have an unknown, unacceptable level of risk, the benchmark dose (BD) with a specified, controlled low level of risk has become popular as an adjunct to the NOAEL or the low observed adverse effect level (LOAEL) in the safety assessment process. The purpose of this paper is to summarize statistical procedures available for calculating BDs and their confidence limits for noncancer endpoints. Procedures are presented and illustrated for quantal (binary), quasicontinuous (proportion), and continuous data. Quasicontinuous data arise in developmental studies where the measure of an effect for a fetus is quantal (normal or abnormal) but the experimental unit is the mother (litter) so that results can be expressed as the proportion of abnormal fetuses per litter. However, the correlation of effects among fetuses within a litter poses some additional statistical problems. Also, developmental studies usually include some continuous measures, such as fetal body weight or length. With continuous data there generally is not a clear demarcation between normal and adverse measurements. In such cases, extremely high and/or low measurements at some designated percentile(s) can be considered abnormal. Then the probability (risk) of abnormal in iduals can be estimated as a function of dose. The procedure for estimating a BD with continuous data is illustrated using neurotoxicity data. When multiple measures of adverse effects are available, a BD can be estimated based on a selected endpoint or the appearance of any combination of endpoints. Multivariate procedures are illustrated using developmental and reproductive toxicity data.
Publisher: Environmental Health Perspectives
Date: 11-1985
DOI: 10.1289/EHP.8563211
Abstract: We present and discuss several methods for analyzing rodent tumorigenicity experiments. Two approaches are based on the age and tumor status (present/absent) of each animal at the time of death, and assume either that the tumor type is nonlethal or instantly lethal. Two other approaches avoid such restrictive assumptions about tumor lethality by requiring additional types of data. One method assumes that animals are randomly sacrificed at various ages throughout the study. The second approach requires that each animal which develops the tumor be classified as dying either from the tumor or from other causes.
Publisher: Springer Science and Business Media LLC
Date: 2013
Publisher: Elsevier BV
Date: 09-2007
Publisher: Oxford University Press (OUP)
Date: 15-06-1993
DOI: 10.1093/OXFORDJOURNALS.AJE.A116644
Abstract: Several studies have reported an association between caffeine intake and delay to conception. To study this relation further, the authors examined caffeine use in 1,050 women with primary infertility and 3,833 women who had recently given birth during the period 1981-1983 in the United States and Canada. The cases were separated by the cause of their infertility: ovulatory factor, tubal disease, cervical factor, endometriosis, or idiopathic infertility. The relative risks of each type of infertility associated with caffeine were calculated using separate logistic regression models and controlling for relevant confounding factors, such as age, center, cigarette smoking, lifetime number of sexual partners, alcohol consumption, contraception, body mass index, and exercise. A significant increase in the risk of infertility due to tubal disease or endometriosis was observed for the upper levels of caffeine intake, indicating a threshold effect. For tubal infertility, a relative risk of 1.5 (95% confidence interval (CI) 1.1-2.0) was found in women who consumed more than 7 g of caffeine per month as compared with those who consumed 3 g or less per month. For endometriosis, the relative risk was 1.9 (95% CI 1.2-2.9) in women who consumed 5.1-7 g/month and 1.6 (95% CI 1.1-2.4) in those with an intake of more than 7 g/month. These data suggest that caffeine deserves further study with regard to its effects on the female reproductive system.
Publisher: Wiley
Date: 23-10-2000
Publisher: JSTOR
Date: 12-1993
DOI: 10.2307/2532240
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2008
Publisher: Springer Science and Business Media LLC
Date: 27-10-2007
Publisher: Elsevier BV
Date: 04-2006
Publisher: Environmental Health Perspectives
Date: 03-2006
DOI: 10.1289/EHP.7916
Abstract: An established exposure-response relationship exists between water arsenic levels and skin lesions. Results of previous studies with limited historical exposure data, and laboratory animal studies suggest that diet may modify arsenic metabolism and toxicity. In this study, we evaluated the effect of diet on the risk of arsenic-related skin lesions in Pabna, Bangladesh. Six hundred cases and 600 controls loosely matched on age and sex were enrolled at Dhaka Community Hospital, Bangladesh, in 2001-2002. Diet, demographic data, and water s les were collected. Water s les were analyzed for arsenic using inductively coupled plasma mass spectroscopy. Betel nut use was associated with a greater risk of skin lesions in a multivariate model [odds ratio (OR) = 1.67 95% confidence interval (CI), 1.18-2.36]. Modest decreases in risk of skin lesions were associated with fruit intake 1-3 times/month (OR = 0.68 95%CI, 0.51-0.89) and canned goods at least 1 time/month (OR = 0.41 95% CI, 0.20-0.86). Bean intake at least 1 time/day (OR = 1.89 95% CI, 1.11-3.22) was associated with increased odds of skin lesions. Betel nut use appears to be associated with increased risk of developing skin lesions in Bangladesh. Increased intake of fruit and canned goods may be associated with reduced risk of lesions. Increased intake of beans may be associated with an increased risk of skin lesions. The results of this study do not provide clear support for a protective effect of vegetable and overall protein consumption against the development of skin lesions, but a modest benefit cannot be excluded.
Publisher: JSTOR
Date: 1987
DOI: 10.2307/2347543
Publisher: American Diabetes Association
Date: 2004
Abstract: OBJECTIVE—To explore the relationship between depressive symptoms and incidence of type 2 diabetes in women. RESEARCH DESIGN AND METHODS—We conducted an analysis of 72,178 female nurses aged 45–72 years who did not have diagnosed diabetes and who answered the Medical Outcomes Study 36-Item Short-Form Health Status Survey (SF-36) at baseline in 1992. We calculated relative risks (RR) of type 2 diabetes for women with presence of depressive symptoms (i.e., Five-Item Mental Health Index [MHI-5] score & ). RESULTS—During 4 years of follow-up (282,317 person-years), 973 incident cases of type 2 diabetes were documented. Age-adjusted RR of developing type 2 diabetes for women with presence of depressive symptoms was 1.55 (95% CI 1.27–1.90). Additional adjustment for BMI resulted in a RR of developing type 2 diabetes of 1.36 (1.11–1.67). The multivariate RR of developing type 2 diabetes was 1.22 (1.00–1.50). After excluding women diagnosed with diabetes between 1992 and 1994, 472 incident cases of type 2 diabetes were documented for the follow-up period from 1994 to 1996 (148,889 person-years). The multivariate RR of developing type 2 diabetes for women with depressive symptoms was 1.29 (0.96–1.72). CONCLUSIONS—Our data suggest that depressive symptoms are associated with a modest increase in the risk of type 2 diabetes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2004
DOI: 10.1097/01.EDE.0000121378.62340.A7
Abstract: It is often difficult and expensive to make direct measurements of an in idual's occupational or environmental exposures in large epidemiologic studies. In this study, we used information collected in validation studies to develop a prediction rule for assessing exposure in a study with no direct measurement. We established a prediction rule through mixed-effect modeling of direct measurement data and information on observable exposure predictors and their interactions. Specifically, we used 383 measures of whole-body vibration from 247 professional taxi drivers and attempted to quantify vibration exposures for in iduals in a large study on low back pain. Using the "jackknife method," we found that our prediction rule had an acceptably low relative prediction error of 11% (95% confidence interval-10-12%). Implementing the prediction rule would result in measurement errors independent of low back pain and of all identified and observable predictors of whole-body vibration. We applied the predicted levels to compute each person's daily exposure, and found a strong association between the predicted daily whole-body vibration exposure and prevalence of low back pain. This supported the construct validity of the exposure prediction rule. The predictive and construct validity of our prediction rule suggests that this general statistical approach can be useful in other occupational settings to improve the quality of exposure assessment.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2009
Publisher: Elsevier BV
Date: 09-1981
DOI: 10.1016/0003-2697(81)90327-4
Abstract: To systematically study the effects of the number of d electrons of the first transition metal ions (Fe, Co, Ni, Cu and Zn) on the formation and stability of metal flavonoid complexes, we took the quercetin/M2+ complex as a model system to investigate the structures and properties of these complexes. Based on considerable structural information obtained through ESI-MSn, all of the first transition metal ions (Fe2+, Co2+, Ni2+, Cu2+ and Zn2+) were found to form different complexes with quercetin, while with the number of chelating flavonoids decreasing along with the reduction of the metal ionic radius. Quercetin forms different complexes with the above metal alent ions through its 5-OH and 4-carbonyl groups the complex stability is highly dependent on both the metallic ion and the flavonoid chelator itself. As for the central ion (M2+), when chelated with quercetin to form the complex, the stability of the complex decreased in the following order: Cu2+ > Ni2+ > Co2+ > Fe2+ > Zn2+. With flavonoid: metal stoichiometries at 2:1, the complexes formed between quercetin and metal ions (Fe2+, Ni2+, Co2+ and Zn2+) have the similar fragmentation mechanism, while Cu2+ displayed different fragmentation mechanism due to the concurrent oxidation.
Publisher: Wiley
Date: 29-09-2015
Abstract: The aim of the study was to determine if oxygen delivered through humidified high flow nasal cannulae (HHFNC) reduced the need for escalation in ventilation management and work of breathing in the ED patients presenting with acute undifferentiated shortness of breath compared with standard oxygen therapy. This was an unblinded randomised control trial conducted at two hospital EDs in Sydney, Australia. Eligible patients presenting with shortness of breath were randomised to HHFNC or standard oxygen therapy. Primary outcomes were the need to escalate ventilation therapy or a reduction in respiratory rate of 20% or more within 2 h of commencement. One hundred patients were enrolled in the trial. The intervention group receiving HHFNC was associated with a higher proportion of patients with a reduced respiratory rate at 2 h (66.7% vs 38.5%, P = 0.005) and a lower proportion of patients requiring escalation in ventilation therapy (4.2% vs 19%, P = 0.02) compared with standard oxygen therapy. The use of high flow nasal cannula oxygenation was associated with improved respiratory state in selected patients presenting to the ED with acute undifferentiated shortness of breath.
Publisher: Springer Science and Business Media LLC
Date: 26-09-2006
Abstract: The mechanisms for the association between birth by cesarean section and atopy and asthma are largely unknown. To examine whether cesarean section results in neonatal secretion of cytokines that are associated with increased risk of atopy and/or asthma in childhood. To examine whether the association between mode of delivery and neonatal immune responses is explained by exposure to the maternal gut flora (a marker of the vaginal flora). CBMCs were isolated from 37 neonates at delivery, and secretion of IL-13, IFN-γ, and IL-10 (at baseline and after stimulation with antigens [dust mite and cat dander allergens, phytohemagglutinin, and lipopolysaccharide]) was quantified by ELISA. Total and specific microbes were quantified in maternal stool. The relation between mode of delivery and cord blood cytokines was examined by linear regression. The relation between maternal stool microbes and cord blood cytokines was examined by Spearman's correlation coefficients. Cesarean section was associated with increased levels of IL-13 and IFN-γ. In multivariate analyses, cesarean section was associated with an increment of 79.4 pg/ml in secretion of IL-13 by CBMCs after stimulation with dust mite allergen (P 0.001). Among children born by vaginal delivery, gram-positive anaerobes and total anaerobes in maternal stool were positively correlated with levels of IL-10, and gram-negative aerobic bacteria in maternal stool were negatively correlated with levels of IL-13 and IFN-γ. Cesarean section is associated with increased levels of IL-13 and IFN-γ, perhaps because of lack of labor and/or reduced exposure to specific microbes (e.g., gram-positive anaerobes) at birth.
Publisher: Elsevier BV
Date: 04-2005
DOI: 10.1016/J.JACI.2004.12.1138
Abstract: Asthma is common in minority and disadvantaged populations, whereas atopic disorders other than asthma appear to be less prevalent. It is unclear whether the same holds true for objective markers of sensitization. To determine the association of asthma, atopic disorders, and specific sensitization with race and socioeconomic factors. We analyzed total and specific IgE among 882 women (577 white, 169 black, and 136 Hispanic) who delivered a child at a large tertiary hospital in Boston, Mass, and who were screened for participation in a family and birth cohort study. Race/ethnicity and other characteristics were obtained from screening questionnaires. Addresses were geocoded, and 3 census-based geographic area socioeconomic variables were derived from block group information from the 1990 US Census. Black and Hispanic women were more likely to come from areas with low socioeconomic indicators and were more likely to have asthma than white women. However, these women were less likely to have hay fever and eczema than their white counterparts. Compared with white women, black women had higher mean total IgE levels had greater proportions of sensitization to indoor, outdoor, and fungal allergens and were more than twice as likely to be sensitized to > or =3 aeroallergens. The racial/ethnic disparities in atopic disorders may represent either underdiagnosis or underreporting and suggest that allergy testing may be underused in some populations. Differences in total IgE levels and specific allergen sensitization are likely a result of the complex interplay between exposures associated with socioeconomic disadvantage.
Publisher: Wiley
Date: 08-1991
Abstract: Exposure to developmental toxicants may cause fetal malformations, increase prenatal death rates and reduce fetal weight at term. However, there has been little formal study of the relationship among these effects. Certainly, no statistical methods are currently available to jointly analyze these effects of exposure. As a preliminary step in developing such methods, simple exploratory analyses were conducted using a series of ten studies conducted for the National Toxicology Program. Because fetal weight and malformation status were both reported for all live fetuses, the data permitted an exploration of the correlation between these two outcomes. The data show a clear pattern wherein malformed fetuses tended to be lighter at term than nonmalformed fetuses. While these patterns cannot be used to draw inferences regarding the biological relationship between fetal weight and malformation, they do suggest the potential value in developing statistical models for the joint effect of exposure on fetal weight and malformations.
Publisher: Elsevier BV
Date: 04-2012
DOI: 10.1016/J.AUEC.2021.04.003
Abstract: To determine the incidence, characteristics (including timeframe) and predictors of patients discharged from the Emergency Department (ED) that later return and require admission. A retrospective cross-sectional study examining all return visits to three EDs in Sydney, Australia, over a 12-month period. Patients returning within 28 days from ED discharge with the same or similar complaint were classified as a return visit to ensure capture of all return visits. Descriptive and inferential statistics were used to analyse the data and logistic regression was performed to predict factors associated with return visits with general admission, and return visits admitted to critical care. There were 1,798 (30%) return visits which resulted in admission, mostly to a non-critical care area (1,679, 93%). The current NSW 48 -h time frame used to define a return visit in NSW captured half of all admitted returns (49.5%) and just over half (59.2%) of critical care admissions. Variables associated with an admission to critical care were age (OR 1.02, 95% CI 1.01, 1.03), initial presentation (index visit) made to a lower level ED (OR 3.76 95% CI 2.06, 6.86), Triage Category 2 (OR 3.67 95% CI 2.04, 6.60) and a cardiac diagnosis (OR 5.76, 95% CI 3.01, 11.01). This model had adequate discriminant ability with AUROC = 0.825. A small number of return visits result in admission, especially to critical care. These patients are at risk of poor outcomes. As such, clinicians should have increased index of suspicion for patients who return that are older, present with cardiac problems, or have previously presented to a lower level ED. Revision of the current timeframe that defines a return visit ought to be considered by policy makers to improve the accuracy of this widely used key performance indicator.
Publisher: Elsevier BV
Date: 11-1999
Publisher: Institute of Mathematical Statistics
Date: 05-1995
Publisher: Elsevier
Date: 1994
Publisher: Springer Science and Business Media LLC
Date: 06-02-2007
Publisher: American Thoracic Society
Date: 2011
Publisher: Wiley
Date: 20-01-2016
DOI: 10.1111/BIOM.12474
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.IENJ.2021.101125
Abstract: Unplanned return visits to the emergency department (ED) have been associated with adverse outcomes and may reflect the quality of care delivered. Several studies speculate the reasons for return and suggest clinician behaviour as potentially influencing a patient's decision to return to the ED. There is little research about this issue from the clinician's perspective, which is necessary to inform future practice improvement. A descriptive cross sectional design was employed to ascertain perspectives on identification and management of return visits occurring within 48 hours of discharge. An electronic survey was distributed to all medical, nursing, and clerical staff at one ED. Descriptive statistics were used for quantitative data and content analysis was performed on textual data. Results were categorised as barriers or facilitators, then mapped to the Theoretical Domains Framework. A response rate of 59.7% (n=86/144) was achieved. Staff reported increased levels of concern for this patient group but not all staff were aware of the policy for managing return patients (40.7%). Five barriers and three facilitators were identified that mapped to eight influencers of behaviour including knowledge, memory and environmental factors. Overall, staff were aware of return patients but lacked familiarity with policy and processes to identify and commence relevant protocols. Further review of current practice as well as the patient perspective is required before any intervention to improve practice is developed.
Publisher: Environmental Health Perspectives
Date: 09-2003
DOI: 10.1289/EHP.6175
Abstract: Scientific and public concern exists about potential reproductive health effects of persistent chlorinated organic chemicals, such as polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), and dichlorodiphenyldichloroethylene (DDE, the most stable daughter compound of DDT). To explore the hypothesis that environmental exposures to PCBs and DDE are associated with altered semen parameters, we conducted a cross-sectional study of 212 male partners of subfertile couples who presented to the Massachusetts General Hospital Andrology Laboratory. Semen parameters were analyzed as both a continuous measure and dichotomized based on World Health Organization reference values for sperm concentration (< 20 million/mL), motility (< 50% motile), and Kruger strict criteria for morphology (< 4% normal). The comparison group for the dichotomized analysis was men with all three semen parameters above the reference values. In serum, 57 PCB congeners and p,p -DDE were measured by congener-specific analysis using gas chromatography with electron capture detection. There were dose-response relationships among PCB-138 and sperm motility (odds ratio per tertile, adjusted for age, abstinence, and smoking, and p-value for trend were, respectively, 1.00, 1.68, 2.35, and p-value = 0.03) and morphology (1.00, 1.36, 2.53, p-value = 0.04). There was limited evidence of an inverse relationship between sum of PCBs, as well as those PCBs classified as cytochrome P450 enzyme inducers, with sperm motility and sperm morphology, as well as limited evidence of an inverse association between p,p -DDE and sperm motility. The lack of a consistent relationship among semen parameters and other in idual PCB congeners and groupings of congeners may indicate a difference in spermatotoxicity between congeners.
Publisher: Elsevier BV
Date: 09-2023
Publisher: Wiley
Date: 11-06-2019
DOI: 10.1002/SIM.8180
Publisher: Wiley
Date: 04-03-2004
DOI: 10.1002/J.1939-4640.2004.TB02790.X
Abstract: The general population is exposed to phthalates through consumer products, diet, and medical devices. The present study explored whether phthalates, reproductive toxins in laboratory animals, were associated with altered sperm movement characteristics in men. Two-hundred twenty subjects provided a semen s le for computer-aided sperm analysis (CASA) and a urine s le for measurement of phthalate monoesters, monoethyl (MEP), monobenzyl (MBzP), mono-n-butyl (MBP), mono-2-ethylhexyl (MEHP), and monomethyl (MMP). Three CASA parameters, straight-line velocity (VSL), curvilinear velocity (VCL), and linearity (LIN), were used as measures of sperm progression, sperm vigor, and swimming pattern, respectively. There were suggestive dose-response relationships (shown as the predicted change in mean sperm motion parameter for the second and third tertiles compared with the first tertile P value for trend) for MBzP with VSL (-2.36 microm/s, -2.81 microm/s P =.09) and VCL (-1.67 microm/s, -2.45 microm/s P =.4). There were suggestive negative associations between MBP and VSL (-3.07 microm/s, -2.87 microm/s P =.08) and VCL (-3.25 microm/s, -3.46 microm/s P =.2), and between MEHP with VSL (-1.09 microm/s, -2.73 microm/s P =.1) and VCL (-0.29 microm/s, -2.93 microm/s P =.3). In contrast to the other phthalates, MEP was positively associated with VSL and VCL but negatively associated with LIN. No consistent relationship was found for MMP and any sperm motion parameter. Although we did not find statistically significant associations, trends between CASA parameters, sperm velocity, and forward progression, and increased urinary levels of MBP, MBzP, and MEHP warrant further follow-up.
Publisher: Oxford University Press (OUP)
Date: 11-2004
Publisher: Springer Science and Business Media LLC
Date: 29-07-2016
Publisher: Wiley
Date: 02-05-2007
DOI: 10.1111/J.1541-0420.2007.00806.X
Abstract: Increasingly used in health-related applications, latent variable models provide an appealing framework for handling high-dimensional exposure and response data. Item response theory (IRT) models, which have gained widespread popularity, were originally developed for use in the context of educational testing, where extremely large s le sizes permitted the estimation of a moderate-to-large number of parameters. In the context of public health applications, smaller s le sizes preclude large parameter spaces. Therefore, we propose a penalized likelihood approach to reduce mean square error and improve numerical stability. We present a continuous family of models, indexed by a tuning parameter, that range between the Rasch model and the IRT model. The tuning parameter is selected by cross validation or approximations such as Akaike Information Criterion. While our approach can be placed easily in a Bayesian context, we find that our frequentist approach is more computationally efficient. We demonstrate our methodology on a study of methylation silencing of gene expression in bladder tumors. We obtain similar results using both frequentist and Bayesian approaches, although the frequentist approach is less computationally demanding. In particular, we find high correlation of methylation silencing among 16 loci in bladder tumors, that methylation is associated with smoking and also with patient survival.
Publisher: Elsevier BV
Date: 04-1992
DOI: 10.1016/0273-2300(92)90047-D
Abstract: The use of the no observed adverse effect level (NOAEL) in setting allowable exposure levels for noncancer endpoints is a source of controversy. Based on computer simulations and empirical studies, several authors have criticized the use of the NOAEL in terms of its sensitivity to s le size and its high s ling variability from experiment to experiment. The purpose of this paper is to derive the statistical distribution of the NOAEL. Using Weibull models, we investigate the impact of the shape of the underlying dose-response curve on the distribution of the NOAEL. The results confirm previous criticisms of the NOAEL and show that average risk levels associated with the NOAEL may be substantial. These results provide additional motivation for developing alternative approaches to risk assessment.
Publisher: Elsevier BV
Date: 2007
DOI: 10.1016/J.SOCSCIMED.2006.09.021
Abstract: Prevalence of child undernutrition remains high in many developing countries. In settings with scarce resources, modifiable maternal social conditions may influence feeding and parenting practices, in turn affecting child growth. This study aims to quantify the association between maternal social support and depression to children's physical growth outcomes in Teresina, Piauí, northeast Brazil. Interviews were conducted with a random s le of 595 mothers of children 6-24 months old in four low-income sections of Teresina, Piauí. We collected data on sociodemographic factors, mothers' social support, mothers' depressive symptomatology, and child's weight and recumbent length. Weight-for-height z-scores (WHZ), height-for-age z-scores (HAZ) and weight-for-age z-scores (WAZ) were calculated using the National Center for Chronic Disease Prevention and Health Promotion Center SAS program based on the 2000 Centers for Disease Control reference growth curves. Multivariable linear regression was used to model the association between maternal social support and depression to child growth, adjusting for biological and socio-demographic variables. Interviewer and neighborhood variation was accounted for through the inclusion of random effects. In adjusted models, material support, measured by number of friends or family members available to mothers when needing food or milk, was related to 0.3 higher average WHZ and 0.2 higher average WAZ in their children. Maternal positive social interaction, which reflects engagement in leisure-time activities with others, was associated with 0.3 higher average WHZ. Mothers' affectionate support was related to 0.2 higher average children's WHZ and WAZ, whereas social support for resolving a conflict was associated with 0.2 lower average HAZ. Maternal depression was not associated with child growth. It is concluded that inadequate growth in children may be sensitive to maternal social support.
Publisher: Mary Ann Liebert Inc
Date: 12-1992
Abstract: Interferons (IFNs)-alpha and -beta were administered to patients with metastatic sarcomas in two different Eastern Cooperative Oncology Group studies. In one study, patients received IFN-alpha 2b, 20 million units/m2 i.v. 5 days/week x 4, then 10 million units s.c.t.i.w. In the second study, patients received IFN-beta ser 180 million units t.i.w. Of 87 patients evaluable for response, there were three responses in 64 patients (5%) treated with IFN-alpha-2b and no responses in 23 patients treated with IFN-beta ser. Severe or life-threatening fatigue with decline in performance status complicated treatment of 37% of patients receiving IFN-alpha 2b and 17% of patients receiving IFN-beta ser. Further investigation of IFNs in sarcomas should depend on evidence from preclinical studies demonstrating synergistic effects of IFNs combined with a cytoreductive modality which has proven activity in these malignancies.
Publisher: Informa UK Limited
Date: 12-2005
Publisher: Wiley
Date: 10-10-2008
Publisher: Wiley
Date: 04-1993
Abstract: The purpose of this study was to determine the effect of transforming growth factor beta 1 (TGF beta 1) on inorganic pyrophosphate (PPi) elaboration from articular tissues to better understand the pathophysiology of calcium pyrophosphate dihydrate (CPPD) crystal deposition in the joint. PPi was measured in the media of adult porcine articular tissue in organ culture and monolayer cultures. TGF beta 1 strongly stimulated PPi elaboration by porcine fibrocartilage and hyaline cartilage. It modestly increased PPi elaboration by ligament, and had no effect on PPi elaborated by synovium. Of all cell types tested in cell culture, only chondrocytes responded to TGF beta 1 by significantly increasing PPi elaboration. TGF beta 1 stimulates PPi elaboration from hyaline cartilage, fibrocartilage, and ligament, indicating that there is in situ CPPD crystal formation in these tissues. The ability of tissues to respond to TGF beta 1 by increasing PPi elaboration correlates with the prevalence of CPPD crystal deposition found clinically. The unique response of chondrocyte monolayers to TGF beta 1 reinforces the key role of the chondrocyte in PPi elaboration in the joint. These findings support an etiologic role for responsiveness to TGF beta 1 in CPPD disease.
Publisher: Informa UK Limited
Date: 1996
Publisher: JSTOR
Date: 1989
DOI: 10.2307/2347683
Publisher: Informa UK Limited
Date: 1996
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2009
Publisher: Oxford University Press (OUP)
Date: 07-2003
Publisher: Wiley
Date: 2008
DOI: 10.1002/SIM.3053
Abstract: The classical statistical paradigm emphasizes the development and application of methods to account for s ling variability. Many modern day applications, however, require consideration of other sources of uncertainty that are not so easy to quantify. This paper presents a case study involving an assessment of the impact of in-utero methylmercury exposure on the Intelligence Quotient (IQ) of young children. We illustrate how familiar techniques such as hierarchical modeling, Bayesian methods and sensitivity analysis can be used to aid decision making in settings that involve substantial uncertainty.
Publisher: MDPI AG
Date: 22-04-2022
Abstract: Time series data from environmental monitoring stations are often analysed with machine learning methods on an in idual basis, however recent advances in the machine learning field point to the advantages of incorporating multiple related time series from the same monitoring network within a ‘global’ model. This approach provides the opportunity for larger training data sets, allows information to be shared across the network, leading to greater generalisability, and can overcome issues encountered in the in idual time series, such as small datasets or missing data. We present a case study involving the analysis of 165 time series from groundwater monitoring wells in the Namoi region of Australia. Analyses of the multiple time series using a variety of different aggregations are compared and contrasted (with single time series, subsets, and all of the time series together), using variations of the multilayer perceptron (MLP), self-organizing map (SOM), long short-term memory (LSTM), and a recently developed LSTM extension (DeepAR) that incorporates autoregressive terms and handles multiple time series. The benefits, in terms of prediction performance, of these various approaches are investigated, and challenges such as differing measurement frequencies and variations in temporal patterns between the time series are discussed. We conclude with some discussion regarding recommendations and opportunities associated with using networks of environmental data to help inform future resource-related decision making.
Publisher: Informa UK Limited
Date: 09-1989
Publisher: Environmental Health Perspectives
Date: 07-2003
DOI: 10.1289/EHP.5756
Abstract: Phthalates are industrial chemicals widely used in many commercial applications. The general population is exposed to phthalates through consumer products as well as through diet and medical treatments. To determine whether environmental levels of phthalates are associated with altered DNA integrity in human sperm, we selected a population without identified sources of exposure to phthalates. One hundred sixty-eight subjects recruited from the Massachusetts General Hospital Andrology Laboratory provided a semen and a urine s le. Eight phthalate metabolites were measured in urine by using high-performance liquid chromatography and tandem mass spectrometry data were corrected for urine dilution by adjusting for specific gravity. The neutral single-cell microgel electrophoresis assay (comet assay) was used to measure DNA integrity in sperm. VisComet image analysis software was used to measure comet extent, a measure of total comet length (micrometers) percent DNA in tail (tail%), a measure of the proportion of total DNA present in the comet tail and tail distributed moment (TDM), an integrated measure of length and intensity (micrometers). For an interquartile range increase in specific gravity-adjusted monoethyl phthalate (MEP) level, the comet extent increased significantly by 3.6 micro m [95% confidence interval (95% CI), 0.74-6.47] the TDM also increased 1.2 micro m (95% CI, -0.05 to 2.38) but was of borderline significance. Monobutyl, monobenzyl, monomethyl, and mono-2-ethylhexyl phthalates were not significantly associated with comet assay parameters. In conclusion, this study represents the first human data to demonstrate that urinary MEP, at environmental levels, is associated with increased DNA damage in sperm.
Publisher: Informa UK Limited
Date: 11-2000
Publisher: Elsevier BV
Date: 2007
DOI: 10.1016/J.JACI.2006.09.002
Abstract: Increased cord blood IgE levels, in conjunction with a family history of atopy, are associated with the development of allergic diseases in children. However, little is known about predictors of cord blood IgE levels. Our objective was to identify predictors of cord blood IgE levels among infants at increased risk of atopy. Cord blood IgE levels were measured in 874 infants who were screened for participation in a birth cohort. Questionnaires were administered after birth of the infant, and maternal and cord blood was obtained for measurement of IgE levels. Logistic and tobit regression models were used to study the association between perinatal factors and cord blood IgE levels. In multivariable models infant male sex, increased maternal total IgE level, maternal allergen sensitization, Hispanic ethnicity, and residence in low-income areas were associated with detectable or increased cord blood IgE levels, whereas increasing maternal age was associated with undetectable or lower cord blood IgE levels. Although maternal smoking during pregnancy was positively associated with cord blood IgE levels in univariable models, the effect did not persist after adjusting for potential confounders. Maternal allergen sensitization, markers of socioeconomic disadvantage and race/ethnicity, maternal age, and infant sex might influence fetal production of IgE. We found no association of maternal parity, mode of delivery, gestational age, or season of birth with cord blood IgE levels. The identification of these definable familial and environmental factors that predict cord blood IgE levels might help in the early detection of infants at risk for atopic disorders.
Publisher: Environmental Health Perspectives
Date: 04-2003
DOI: 10.1289/EHP.5878
Abstract: Stressors as subtle as night work or shift work can lead to irregular menstrual cycles, and changes in reproductive hormone profiles can adversely affect bone health. This study was conducted to determine if stresses associated with the disruption of regular work schedule can induce alterations in ovarian function which, in turn, are associated with transient bone resorption. Urine s les from 12 rotating shift workers from a textile mill in Anqing, China, were collected in 1996-1998 during pairs of sequential menstrual cycles, of which one was longer than the other (28.4 vs. 37.4 days). Longer cycles were characterized by a prolonged follicular phase. Work schedules during the luteal-follicular phase transition (LFPT) preceding each of the two cycles were evaluated. All but one of the shorter cycles were associated with regular, forward phase work shift progression during the preceding LFPT. In contrast, five longer cycles were preceded by a work shift interrupted either by an irregular shift or a number of "off days." Urinary follicle-stimulating hormone levels were reduced in the LFPT preceding longer cycles compared with those in the LFPT preceding shorter cycles. There was greater bone resorption in the follicular phase of longer cycles than in that of shorter cycles, as measured by urinary deoxypyridinoline. These data confirm reports that changes in work shift can lead to irregularity in menstrual cycle length. In addition, these data indicate that there may be an association between accelerated bone resorption in menstrual cycles and changes of regularity in work schedule during the preceding LFPT.
Publisher: Informa UK Limited
Date: 09-2004
Publisher: American Thoracic Society
Date: 07-2002
DOI: 10.1164/RCCM.2109074
Abstract: Five retrospective studies have reported an association between antibiotic use in early life and asthma in childhood. We studied the relationship between the use of oral antibiotics in the first year of life and asthma, allergic rhinitis, and eczema at age 5 years among 448 children with a parental history of atopy monitored from birth. After adjustment for potential confounders, we found no significant association between antibiotic use in the first year of life and asthma (odds ratio [OR] for one versus no courses of antibiotics, 0.5 95% confidence interval [CI] for OR, 0.2 to 1.5 OR for two or more versus no courses of antibiotics, 1.0 95% CI for OR, 0.5 to 2.2), recurrent wheezing, allergic rhinitis, or eczema at age 5 years. There was no significant association between antibiotic use in the first year of life and having at least one of three atopic diseases (asthma, allergic rhinitis, or eczema) at age 5 years (OR for one versus no courses of antibiotics, 0.7 95% CI, 0.4 to 1.4 OR for two or more versus no courses of antibiotics, 0.9 95% CI, 0.5 to 1.4). Our findings do not support the hypothesis that antibiotic use in early life is associated with the subsequent development of asthma and atopy in childhood.
Publisher: Wiley
Date: 07-2001
DOI: 10.1046/J.1365-3016.2001.00009.X
Abstract: Preterm delivery (PTD) appears to be a complex trait determined by both genetic and environmental factors. Few studies have examined genetic influence on PTD. The overall goal of our study is to examine major candidate genes of PTD and to test gene-environment interactions. Our study includes 500 preterm trios, including 500 preterm babies and their parents and 500 maternal age-matched term controls. We will perform the transmission/disequilibrium test (TDT) on candidate genes thought to be important in each of the four biological pathways of PTD: (1) decidual chorioamionotic inflammation: interleukin 1 (IL-1), IL-6, and tumour necrosis factor (TNF) (2) maternal and fetal stress: corticotropin-releasing hormone (CRH) (3) uteroplacental vascular lesions: methylenetereahydrofolate reductase (MTHFR) and (4) susceptibility to environmental toxins: GSTM1, GSTT1, CYP1A1, CYP2D6, CYP2E1, NAT2, NQO1, ALDH2, and EPHX. We will also perform standard case-control analyses on the 500 preterm cases and 500 term controls to examine gene-environment interactions. The major environmental, nutritional and social factors as well as clinical variables known or suspected to be associated with PTD will be used to test for gene-environment interactions. This study integrates epidemiological and clinical data as well as genetic markers along major pathogenic pathways of PTD. The findings from this study should improve our understanding of genetic influences on PTD and gene-environment interactions.
Publisher: Wiley
Date: 09-2001
DOI: 10.1111/J.0006-341X.2001.00941.X
Abstract: The problem of testing a dose-response relationship in the presence of exchangeably correlated binary data has been addressed using a variety of models. Most commonly used approaches are derived from likelihood or generalized estimating equations and rely on large-s le theory to justify their inferences. However, while earlier work has determined that these methods may perform poorly for small or sparse s les, there are few alternatives available to those faced with such data. We propose an exact trend test for exchangeably correlated binary data when groups of correlated observations are ordered. This exact approach is based on an exponential model derived by Molenberghs and Ryan (1999) and Ryan and Molenberghs (1999) and provides natural analogues to Fisher's exact test and the binomial trend test when the data are correlated. We use a graphical method with which one can efficiently compute the exact tail distribution and apply the test to two ex les.
Publisher: Wiley
Date: 11-1987
DOI: 10.1002/1097-0142(19871101)60:9<2141::AID-CNCR2820600903>3.0.CO;2-4
Abstract: Of 86 patients entered in an Eastern Cooperative Oncology Group (ECOG) random Phase II study of mitoxantrone (DHAD) and cisplatin (DDP) in primary liver cancer, 69 were eligible. Nine of the 13 ineligible patients were excluded after a pathology review. Sixty-one percent of the patients were North American, and 39% were South African. The most common severe or the worst toxicity on DHAD was hematologic and to DDP, hematologic and vomiting. Of the 69 eligible patients, 21 experienced severe, life-threatening or fatal toxic reactions. Two patients treated with DDP had partial responses. With a 95% confidence interval, the true response rate to DHAD was less than 8%, and to DDP, less than 17%. The median survival time was 14 weeks on both drugs. Assuming a proportional hazards model, factors that are significantly associated with survival are patient performance status, the presence of the symptoms, raised bilirubin and hepatomegaly, and clinical evidence of cirrhosis. Any differences between survival rates for South African and North American patients were largely explainable by these factors.
Publisher: Springer Science and Business Media LLC
Date: 12-1998
Abstract: Seventy-three eligible, chemotherapy-naive, ambulatory patients with advanced pancreatic carcinoma were allocated to one of two treatment regimens: 35 received PALA (1250 mg/m2 daily x 5 every 4 weeks) and 38 were given SAM (streptozotocin 400 mg/m2 i.v. daily x 5, doxorubicin 45 mg/m2 i.v. on day 1 and 22, and methyl CCNU 60 mg/m2 orally on days 1 and 22 every 6 weeks). Doses were modified for myelo-, gi-, or cardiotoxicity. Adequate organ, bone marrow and cardiac function a measurable lesion adequate caloric intake and a life expectancy of 2 months were required for treatment on this trial. One patient on each regimen had a partial response for response rates of 3% (95% confidence intervals, 0.08 to 17%). Median survival on the PALA arm was 5 months and median time to treatment failure was 2.6 months. SAM patients experienced median overall and progression free survivals of 3.4 and 1.9 months, respectively. The severe toxicity observed was almost exclusively myelosuppression on both regimens. One patient receiving SAM had lethal leukopenic sepsis during the first cycle as the only treatment-related death. Neither PALA nor SAM offer any therapeutic utility to patients with advanced pancreatic cancer.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 2000
DOI: 10.1200/JCO.2000.18.1.148
Abstract: PURPOSE: A randomized phase III clinical trial of adjuvant active specific immunotherapy (ASI) with an autologous tumor cell–bacillus Calmette-Guérin (BCG) vaccine was conducted to determine whether surgical resection plus ASI was more beneficial than resection alone in stage II and III colon cancer patients. PATIENTS AND METHODS: Patients (n = 412) with colon cancer (297 with stage II disease, 115 with stage III disease) were randomly allocated to an observation arm or to a treatment arm in which they received three weekly intradermal vaccine injections of 10 7 irradiated autologous tumor cells beginning approximately 4 weeks after surgery. The first two weekly injections also contained 10 7 BCG organisms. Patients were observed for determination of time to recurrence and disease-free and overall survival. RESULTS: This was a negative study in that after a 7.6-year median follow-up period, there were no statistically significant differences in clinical outcomes between the treatment arms. However, there were disease-free survival (P = .078) and overall survival (P = .12) trends in favor of ASI when treatment compliance was evaluated, ie, patients who received the intended treatment had a delayed cutaneous hypersensitivity (DCH) response to the third vaccination (induration ≥5 mm). Also, the magnitude of the DCH response correlated with improved prognosis. The 5-year survival proportion was 84.6% for those with indurations greater than 10 mm, compared with 45.0% for those with indurations less than 5 mm. CONCLUSIONS: When all randomized patients were evaluated, no significant clinical benefit was seen with ASI in surgically resected colon cancer patients with stage II or III colon cancer. However, there was an indication that treatment compliance with effective immunization results in disease-free and overall survival benefits.
Publisher: Springer Science and Business Media LLC
Date: 09-1997
DOI: 10.1007/BF02694505
Publisher: Wiley
Date: 12-2005
DOI: 10.1111/J.1541-0420.2005.00376.X
Abstract: In an accelerated longitudinal design (ALD), in iduals enter the study at different points of their growth trajectory and are observed over a short time span relative to the entire time span of interest. ALD data are combined across independent units to provide an estimate of an overall population curve and predictions of in idual patterns of change. As a modest extension of the work of Ruppert et al. (2003, Semiparametric Regression, Cambridge University Press), we develop a computationally efficient procedure for the application of longitudinal semiparametric methods under ALD s ling schemes. We compare balanced and complete longitudinal designs to ALDs using the Berkeley Growth Study data and apply our method to longitudinal magnetic resonance imaging (MRI) brain structure size (volume) measurements from an ongoing developmental study. Potential applications extend beyond growth studies to many other fields in which cost and feasibility constraints impose restrictions on s le size and on the numbers and timings of repeated measurements across subjects.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 09-1989
DOI: 10.1200/JCO.1989.7.9.1208
Abstract: In this phase II trial, 105 eligible patients with no prior chemotherapy and advanced sarcoma received doxorubicin, ifosfamide, and dacarbazine (DTIC) with mesna uroprotection (MAID). Starting doses of these drugs were 60, 7,500, and 900 mg/m2 ided over 72 hours by continuous infusion, respectively. Mesna was given for 84 to 96 hours at 2,500 mg/m2/d. Myelosuppression was dose limiting, causing the only toxic death (sepsis). Nonhematologic toxicity consisted predominantly of anorexia and vomiting. Severe mucositis, macroscopic hematuria, renal tubular acidosis, renal failure, and CNS toxicity occurred in less than 5% of cycles. No cardiotoxicity was detected. The overall response rate (10% complete response [CR]) was 47% (95% confidence intervals, 5% to 18% and 37% to 57%, respectively). Most responses (approximately 70%) were observed within two cycles. Median times to progression were 10 and 9 months, respectively. Histologic high tumor grade, lesions less than 5 cm, and less than 1 year from diagnosis to study entry correlated with the probability of response. The median survival was 16 months. Time from diagnosis to study entry, performance status, and extent of disease, but not histologic grade, correlated with survival. Following CR, two patients remain disease-free at 32 and 16 months. Of the 15 additional patients rendered disease-free with surgery, two remain disease-free at 30 and 18 months with no further therapy. While most relapses occurred in sites of prior involvement, death from CNS metastases occurred in 11 of the 80 patients with high-grade sarcomas, of whom seven were still responding systematically (three complete responders). Because of its substantial response in this phase II trial, the MAID regimen is being compared with doxorubicin and DTIC alone in advanced sarcomas and to observation in the adjuvant treatment of high-grade sarcomas in randomized trials.
Publisher: Springer Science and Business Media LLC
Date: 2003
Abstract: The mechanism of arsenic detoxification in humans remains unclear. Data are especially lacking for low-level arsenic exposure. We hypothesize that arsenic methylation ability, defined as the ratios of monomethylarsonic acid (MMA(V))/inorganic arsenic (primary arsenic methylation index, PMI) and dimethylarsinic acid (DMA(V))/ MMA(V) (secondary arsenic methylation index, SMI), may modify the association between cumulative arsenic exposure (CAE, mg/L-year) and the risk of bladder cancer. In this study we investigated the relationship among arsenic methylation ability, CAE, and the risk of bladder cancer in a hospital-based case-control study in southwestern Taiwan. From January 1996 to December 1999 we identified 49 patients with newly diagnosed cases of bladder cancer at the National Cheng-Kung University (NCKU) Medical Center controls consisted of 224 fracture and cataract patients selected from the same medical center. The levels of four urinary arsenic species: arsenite (As(III)), arsenate (As(V)), MMA(V), and DMA(V)) were determined in all subjects by using the high-performance liquid chromatography hydride-generation atomic absorption spectrometry (HPLC-HGAAS). CAE was estimated by using published data collected in a survey from 1974 to 1976. Compared to a CAE 12 mg/L-year was associated with an increased risk of bladder cancer (multivariate odds ratio (OR) 4.23, 95% confidence interval (CI) 1.12-16.01), in the setting of a low SMI (< or = 4.8). Compared to women, smoking men (OR 6.23, 95% CI 1.88-20.62) and non-smoking men (OR 3.25, 95% CI 0.95-11.06) had higher risks of bladder cancer. Given the same level of PMI, smoking men (OR 9.80, 95% CI 2.40-40.10) and non-smoking men (OR 4.45, 95% CI 1.00-19.84) had a higher risk of bladder cancer when compared to women. With the same level of SMI, both smoking men (OR 6.28, 95% CI 1.76-22.39) and non-smoking men (OR 3.31, 95% CI 0.84-12.97) had a higher risk of bladder cancer when compared to women. Subjects with low SMI have a substantially increased risk of bladder cancer, especially when combined with high CAE levels.
Publisher: Oxford University Press (OUP)
Date: 05-2002
Abstract: Although the comet assay has potential value for measuring DNA damage in large epidemiological human sperm studies, it is impractical to perform the assay daily on fresh semen s les. Therefore, before its use in epidemiological studies, the reliability of the comet assay in measuring DNA damage in cryopreserved sperm should be compared with that in fresh human sperm. Semen s les from 16 men were cryopreserved in liquid nitrogen (LN) using four methods: flash freezing with and without cryopreservative, and programmable freezing with and without cryopreservative. Neutral microgel electrophoresis was performed and comets were stained with YOYO-1. Comet length was measured using an eyepiece micrometer at x400 magnification. The highest correlation was between comet assay results obtained from fresh human semen compared with semen flash frozen without cryopreservative (R = 0.88). However, the method of cryopreservation, as compared with other sources of variability, accounted for only 6% of the variability. Inter-in idual variability accounted for 20%, and in idual sperm-to-sperm variability within an ejaculate accounted for 65%. Flash-freezing in LN without cryopreservative most closely reproduced the results obtained using fresh human semen s les, and thereby represents the most appropriate cryopreservation method for human semen in epidemiological studies utilizing the neutral comet assay.
Publisher: Informa UK Limited
Date: 03-2006
Publisher: Oxford University Press (OUP)
Date: 26-10-2010
DOI: 10.1111/J.1467-9876.2010.00737.X
Abstract: The paper describes the use of a longitudinal tobit model to characterize cognitive decline over a 13-year period in a cohort of 2087 elderly Australians. Use of a tobit formulation allows for the so-called ‘ceiling effect’ wherein many subjects achieve perfect test scores. A Bayesian hierarchical joint model is presented that allows for random subject-specific intercepts and slopes, as well as for informative dropout. Results suggest several potential areas of intervention. For ex le, there is a clear dose–response effect of exercise whereby increasing levels of exercise are associated with higher cognitive scores.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 07-1993
DOI: 10.1200/JCO.1993.11.7.1269
Abstract: This three-armed phase III study in adults with advanced soft tissue sarcomas was planned as a comparison of objective regression rates, toxicity, and survival of patients receiving doxorubicin alone, ifosfamide plus doxorubicin, and mitomycin plus doxorubicin plus cisplatin. Between December 1987 and July 1990, 279 patients with histologically confirmed sarcomas were enrolled to receive treatment A (doxorubicin 80 mg/m2), treatment B (ifosfamide 7.5 g/m2 plus doxorubicin 60 mg/m2), or treatment C (mitomycin 8 mg/m2 plus doxorubicin 40 mg/m2 plus cisplatin 60 mg/m2). Of 262 assessable patients, 74 (29%) achieved objective tumor regression. Objective regression occurred in 20% of the 90 patients who received doxorubicin alone (complete remission [CR] rate, 2%), in 34% of the 88 who received ifosfamide plus doxorubicin (CR rate, 3%), and in 32% of the 84 who received mitomycin plus doxorubicin plus cisplatin (CR rate, 7%). With grade 3 or greater myelosuppression in 53% of group A, 80% of group B, and 55% of group C, regimen B was significantly more myelosuppressive than either regimen A or C (P = .01) with two, three, and one treatment-related deaths, respectively. Synovial sarcomas were responsive to ifosfamide plus doxorubicin, especially among patients younger than 40 years of age. Ifosfamide plus doxorubicin produced a significantly higher regression rate (P = .03) than did doxorubicin alone however, this was achieved at a level of myelosuppression significantly more intense than that produced by the single agent or by the three-drug combination. Mitomycin, doxorubicin, and cisplatin also appeared to be more active than the single agent however, at a myelosuppression level similar to that of doxorubicin alone, this trend (P = .07) did not attain the usual level for significance. No significant survival differences were observed.
Publisher: Elsevier BV
Date: 11-1997
Abstract: The Functional Observational Battery (FOB) is a neurotoxicity screening assay composed of 25-30 descriptive, scalar, binary, and continuous endpoints. These outcomes have been grouped into six biologically logical domains as a means to interpret the neuroactive properties of tested chemicals (V. C. Moser, 1992, J. Am. Coll. Toxicol. 10(6), 661-669). However, no data-based exploration of these functional domains has been done. We investigated the degree to which experimental data correspond to the domain groupings by examining severity scores from 10 chemicals tested using a standardized protocol for acute exposure (V. C. Moser et al., 1995, J. Toxicol. Environ. Health 45, 173-210) and identifying endpoint groupings (factors) that best describe the interrelationships in the data, allowing a statistical assessment of whether the FOB endpoints break into domains. We also used a standard measure of bivariate association to confirm the results of the factor analysis. Our results show that while there are clear relationships among variables that compose some domains, there is often substantial correlation among endpoints in different domains. In addition, we investigated a related issue concerning the relative power of the chosen endpoint groupings for identifying significant domain effects. Results from a randomization analysis of the 10 chemicals suggest that the neurophysiologic domain structuring may provide some degree of statistical efficiency for identifying effects.
Publisher: Springer Science and Business Media LLC
Date: 21-10-2009
Publisher: Wiley
Date: 02-2011
DOI: 10.5694/J.1326-5377.2011.TB02940.X
Abstract: To describe the use of surveillance and forecasting models to predict and track epidemics (and, potentially, pandemics) of influenza. We collected 5 years of historical data (2005-2009) on emergency department presentations and hospital admissions for influenza-like illnesses (International Classification of Diseases [ICD-10-AM] coding) from the Emergency Department Information System (EDIS) database of 27 Queensland public hospitals. The historical data were used to generate prediction and surveillance models, which were assessed across the 2009 southern hemisphere influenza season (June-September) for their potential usefulness in informing response policy. Three models are described: (i) surveillance monitoring of influenza presentations using adaptive cumulative sum (CUSUM) plan analysis to signal unusual activity (ii) generating forecasts of expected numbers of presentations for influenza, based on historical data and (iii) using Google search data as outbreak notification among a population. All hospitals, apart from one, had more than the expected number of presentations for influenza starting in late 2008 and continuing into 2009. (i) The CUSUM plan signalled an unusual outbreak in December 2008, which continued in early 2009 before the winter influenza season commenced. (ii) Predictions based on historical data alone underestimated the actual influenza presentations, with 2009 differing significantly from previous years, but represent a baseline for normal ED influenza presentations. (iii) The correlation coefficients between internet search data for Queensland and statewide ED influenza presentations indicated an increase in correlation since 2006 when weekly influenza search data became available. This analysis highlights the value of health departments performing surveillance monitoring to forewarn of disease outbreaks. The best system among the three assessed was a combination of routine forecasting methods coupled with an adaptive CUSUM method.
Publisher: Environmental Health Perspectives
Date: 03-2009
DOI: 10.1289/EHP.11251
Publisher: Oxford University Press (OUP)
Date: 06-2001
Abstract: The estimation of the incidence of tumours in an animal carcinogenicity study is complicated by the occult nature of the tumours involved (i.e. tumours are not observable before an animal’s death). Also, the lethality of tumours is generally unknown, making the tumour incidence function non-identifiable without interim sacrifices, cause-of-death data or modelling assumptions. Although Kaplan–Meier curves for overall survival are typically displayed, obtaining analogous plots for tumour incidence generally requires fairly elaborate model fitting. We present a case-study of tetrafluoroethylene to illustrate a simple method for estimating the incidence of tumours as a function of more easily estimable components. One of the components, tumour prevalence, is modelled by using a generalized additive model, which leads to estimates that are more flexible than those derived under the usual parametric models. A multiplicative assumption for tumour lethality allows for the incorporation of concomitant information, such as the size of tumours. Our approach requires only terminal sacrifice data although additional sacrifice data are easily accommodated. Simulations are used to illustrate the estimator proposed and to evaluate its properties. The method also yields a simple summary measure of tumour lethality, which can be helpful in interpreting the results of a study.
Publisher: Wiley
Date: 12-03-2023
DOI: 10.1111/JAN.15617
Abstract: The aim of this study was to explore the reasons for and experiences of patients who make an unplanned return visit to the emergency department. This study forms the qualitative phase of a larger explanatory sequential mixed methods study and is informed by interpretive description. The paper was prepared using the consolidated criteria for reporting qualitative research. Semi‐structured patient interviews were conducted over a 3‐month period (July–September 2021). Data were analysed using reflexive thematic analysis. Interviews from 13 participants generated findings related to experiences at and following their initial visit that contributed to their decision to return to the emergency department. Four themes were developed: (1) Patients experience barriers to feeling heard and having their concerns addressed (2) Patients have little choice but to place their trust in clinicians (3) Patients unexpectedly experience persistent symptoms which cannot be managed at home and (4) Patients develop a sense of urgency about having their condition treated. A negative experience at the initial ED visit may have dual conflicting impacts. It can contribute to patients' perceived need for a return visit because they are ill‐equipped to manage their condition at home, and it can also contribute to their initial reluctance to return to the ED when symptoms persist. Nurses and other clinicians working in ED need to actively build patient's experiential trust through clear communication, timely consultation and shared decision‐making at discharge, which in turn can increase patient's confidence and capability to self‐manage their condition. This study adds to the current body of literature about return visits by highlighting that a more positive experience of ED may assist patients to make better‐informed decisions about when and how to seek treatment and minimize unnecessary and unplanned return visits. Whilst not an intended topic for exploration in this study, the COVID‐19 pandemic influenced patients' experiences at both initial and return ED visits and limited their ability to access primary healthcare options. These experiences contributed to patients' decisions to make a return visit.
Publisher: Environmental Health Perspectives
Date: 10-2005
DOI: 10.1289/EHP.7844
Abstract: Studies have repeatedly demonstrated that sensitization to fungi, such as Alternaria, is strongly associated with allergic rhinitis and asthma in children. However, the role of exposure to fungi in the development of childhood allergic rhinitis is poorly understood. In a prospective birth cohort of 405 children of asthmatic/allergic parents from metropolitan Boston, Massachusetts, we examined in-home high fungal concentrations (> 90th percentile) measured once within the first 3 months of life as predictors of doctor-diagnosed allergic rhinitis in the first 5 years of life. In multivariate Cox regression analyses, predictors of allergic rhinitis included high levels of dust-borne Aspergillus [hazard ratio (HR) = 3.27 95% confidence interval (CI), 1.50-7.14], Aureobasidium (HR = 3.04 95% CI, 1.33-6.93), and yeasts (HR = 2.67 95% CI, 1.26-5.66). The factors controlled for in these analyses included water damage or mild or mildew in the building during the first year of the child's life, any lower respiratory tract infection in the first year, male sex, African-American race, fall date of birth, and maternal IgE to Alternaria > 0.35 U/mL. Dust-borne Alternaria and nonsporulating and total fungi were also predictors of allergic rhinitis in models excluding other fungi but adjusting for all of the potential confounders listed above. High measured fungal concentrations and reports of water damage, mold, or mildew in homes may predispose children with a family history of asthma or allergy to the development of allergic rhinitis.
Publisher: Elsevier BV
Date: 08-1998
Publisher: American Academy of Pediatrics (AAP)
Date: 09-2004
Abstract: Background. Perinatal factors, including gestational age and birth weight, influence the development of atopy in early life. However, the role of these factors in the development of asthma in later life among children who do not develop perinatal respiratory disease remains unclear. Methods. Four hundred fifty-four infants who had a history of allergy or asthma in at least 1 parent, were born in the 36th week of gestation or later, and did not develop perinatal respiratory distress were monitored for at least 6 years. Associations between predictor variables and asthma and wheeze were assessed with multivariate logistic regression and repeated-event analyses. Results. Although we previously observed a relationship between low birth weight and persistent wheeze in the first 1 year of life, we did not observe similar associations between low birth weight and asthma at 6 years of age (odds ratio [OR]: 1.05 95% confidence interval [CI]: 0.40–2.73). However, a strong relationship was found between low-normal gestational age and asthma at 6 years of age (OR: 4.7 95% CI: 2.1–10.5). The effects of low-normal gestational age were significantly greater among boys than among girls (boys: OR: 8.15 95% CI: 2.98–22.3 girls: OR: 1.90 95% CI: 0.38–13.83). Longitudinal analysis of the relationship between gestational age and wheeze during the 6 years of observation confirmed these gender differences. Conclusions. Among children at high risk of developing atopic disease, late prematurity might be an important additional determinant of asthma later in life, and these effects are gender specific.
Publisher: Informa UK Limited
Date: 30-12-2010
Publisher: Wiley
Date: 12-2005
DOI: 10.1111/J.1541-0420.2005.00364.X
Abstract: The case-cohort design for longitudinal data consists of a subcohort s led at the beginning of the study that is followed repeatedly over time, and a case s le that is ascertained through the course of the study. Although some members in the subcohort may experience events over the study period, we refer to it as the "control-cohort." The case s le is a random s le of subjects not in the control-cohort, who have experienced at least one event during the study period. Different correlations among repeated observations on the same in idual are accommodated by a two-level random-effects model. This design allows consistent estimation of all parameters estimable in a cohort design and is a cost-effective way to study the effects of covariates on repeated observations of relatively rare binary outcomes when exposure assessment is expensive. It is an extension of the case-cohort design (Prentice, 1986, Biometrika73, 1-11) and the bidirectional case-crossover design (Navidi, 1998, Biometrics54, 596-605). A simulation study compares the efficiency of the longitudinal case-cohort design to a full cohort analysis, and we find that in certain situations up to 90% efficiency can be obtained with half the s le size required for a full cohort analysis. A bootstrap method is presented that permits testing for intra-subject homogeneity in the presence of unidentifiable nuisance parameters in the two-level random-effects model. As an illustration we apply the design to data from an ongoing study of childhood asthma.
Publisher: Oxford University Press (OUP)
Date: 1993
Publisher: Wiley
Date: 08-08-2016
DOI: 10.1002/SIM.7071
Abstract: Most of the few published models used to obtain small-area estimates of relative survival are based on a generalized linear model with piecewise constant hazards under a Bayesian formulation. Limitations of these models include the need to artificially split the time scale, restricted ability to include continuous covariates, and limited predictive capacity. Here, an alternative Bayesian approach is proposed: a spatial flexible parametric relative survival model. This overcomes previous limitations by combining the benefits of flexible parametric models: the smooth, well-fitting baseline hazard functions and predictive ability, with the Bayesian benefits of robust and reliable small-area estimates. Both spatially structured and unstructured frailty components are included. Spatial smoothing is conducted using the intrinsic conditional autoregressive prior. The model was applied to breast, colorectal, and lung cancer data from the Queensland Cancer Registry across 478 geographical areas. Advantages of this approach include the ease of including more realistic complexity, the feasibility of using in idual-level input data, and the capacity to conduct overall, cause-specific, and relative survival analysis within the same framework. Spatial flexible parametric survival models have great potential for exploring small-area survival inequalities, and we hope to stimulate further use of these models within wider contexts. Copyright © 2016 John Wiley & Sons, Ltd.
Publisher: Oxford University Press (OUP)
Date: 03-2001
Abstract: The analysis of animal carcinogenicity data is complicated by various statistical issues. A topic of recent debate is how to control for the effect of the animal’s body weight on the outcome of interest, the onset of tumours. We propose a method which incorporates historical information from the control animals in previously conducted experiments. We allow non-linearity in the effects of body weight by modelling the relationship nonparametrically through a penalized spline. A simple extension of the penalized spline model allows the relationship between weight and the onset of tumour to vary from one experiment to another.
Publisher: Institute of Mathematical Statistics
Date: 05-1995
Publisher: Springer Science and Business Media LLC
Date: 12-1999
DOI: 10.1007/BF02785872
Publisher: Oxford University Press (OUP)
Date: 18-02-2013
Publisher: Informa UK Limited
Date: 06-2004
Publisher: Wiley
Date: 09-2023
DOI: 10.1111/ANZS.12397
Publisher: Wiley
Date: 10-1989
Abstract: Clinicians often wish to use data from clinical trials or hospital databases to study disease natural history. Of particular interest are estimated survival and prognostic factors. In this context, it may be appropriate to measure survival from diagnosis or some other time origin, possibly prior to study entry. We describe the application of methods for truncated survival data, and compare these with the standard product limit estimator and proportional hazards models in the measurement of survival from entry. Theoretical considerations suggest that analysis of survival from entry may under- or overestimate the survival distribution of interest, depending on the shape of the true underlying hazard. Analogous results hold for the coefficients from a proportional hazards model. We illustrate our findings with data from a multicenter clinical trial and a hospital database.
Publisher: Elsevier
Date: 1999
Publisher: Wiley
Date: 11-1998
DOI: 10.1002/(SICI)1097-0142(19981101)83:9<1908::AID-CNCR5>3.0.CO;2-6
Abstract: To assess the toxicity, local response, and survival associated with multimodality therapy in a cooperative group setting, patients with biopsy-proven clinical Stage I or II adenocarcinoma of the esophagus (staged according to 1983 American Joint Committee on Cancer criteria) or gastroesophageal junction were treated with concomitant radiation and chemotherapy followed by esophagectomy. Radiotherapy was administered in daily 2-gray (Gy) fractions 5 days a week until a total of 60 Gy was reached. 5-fluorouracil (5-FU) was infused continuously at a dose of 1000 mg/m2/day for 96 hours on Days 2-5 and 28-31. On Day 2, a 10 mg/m2 bolus of mitomycin was injected intravenously. Esophagectomy was performed 4-8 weeks following completion of the radiotherapy. During the 18-month study period (August 1991 through January 1993), 46 eligible patients were accrued from 21 institutions. Eight patients were Stage I and 38 Stage II. Eighty-seven percent of patients (40 of 46) received 6000 centigray (cGy), and all received >5000 cGy. Seventy-eight percent of patients (36 of 46) received >90% of the planned 5-FU dose. Follow-up ranged from 11 to 36 months (median, 22 months). There were eight treatment-related deaths two were preoperative (from adult respiratory distress syndrome) and six were postoperative. Complete or partial response prior to esophagectomy was observed in 63% of cases, stable disease in 15%, and progression in 20%. Thirty-three patients underwent esophagectomy (transhiatal, n=14 Ivor Lewis, n=16 other, n=3). No tumor was found in the specimens resected from 8 of these 33 patients this represented a pathologic complete response rate of 17% overall and 24% for those who underwent esophagectomy. Overall median survival was 16.6 months, 1-year survival 57%, and 2-year survival 27%. Survival was significantly worse for patients with circumferential cancers (median, 18.1 months vs. 8.3 months P <0.05). High dose radiation therapy with concurrent 5-FU and mitomycin may be administered to patients with esophageal adenocarcinoma with acceptable morbidity. However, in a cooperative group setting, esophagogastrectomy following intensive chemoradiotherapy is associated with excessive morbidity and mortality. Circumferential tumor growth is a significant adverse prognostic factor.
Publisher: Elsevier
Date: 2000
Publisher: Environmental Health Perspectives
Date: 11-2005
DOI: 10.1289/EHP.7632
Abstract: Endotoxin exposure has been proposed as an environmental determinant of allergen responses in children. To better understand the implications of using a single measurement of house dust endotoxin to characterize exposure in the first year of life, we evaluated room-specific within-home and between-home variability in dust endotoxin obtained from 470 households in Boston, Massachusetts. Homes were s led up to two times over 5-11 months. We analyzed 1,287 dust s les from the kitchen, family room, and baby's bedroom for endotoxin. We fit a mixed-effects model to estimate mean levels and the variation of endotoxin between homes, between rooms, and between s ling times. Endotoxin ranged from 2 to 1,945 units per milligram of dust. Levels were highest during summer and lowest in the winter. Mean endotoxin levels varied significantly from room to room. Cross-sectionally, endotoxin was moderately correlated between family room and bedroom floor (r = 0.30), between family room and kitchen (r = 0.32), and between kitchen and bedroom (r = 0.42). Adjusting for season, the correlation of endotoxin levels within homes over time was 0.65 for both the bedroom and kitchen and 0.54 for the family room. The temporal within-home variance of endotoxin was lowest for bedroom floor s les and highest for kitchen s les. Between-home variance was lowest in the family room and highest for kitchen s les. Adjusting for season, within-home variation was less than between-home variation for all three rooms. These results suggest that room-to-room and home-to-home differences in endotoxin influence the total variability more than factors affecting endotoxin levels within a room over time.
Publisher: BMJ
Date: 1998
DOI: 10.1136/OEM.55.1.31
Abstract: To assess the association between petrochemical exposure and spontaneous abortion, a retrospective epidemiological study in a large petrochemical complex in Beijing, China was conducted. Plant employment records identified 3105 women who were married, were 20-44 years of age, and had never smoked. Of those, 3070 women (98.8%) reported at least one pregnancy. From this group, 2853 (93%) of the women participated in the study. According to their plant employment record, about 57% of these women workers reported occupational exposure to petrochemicals during the first trimester of their pregnancy. Trained interviewers administered a standardised questionnaire to this group of women and their husbands, collecting information on reproductive history, pregnancy outcomes, employment history, occupational exposure, smoking habits, alcohol consumption, indoor air pollution, and demographic variables. The results from the womens' first pregnancies were analysed. There was a significantly increased risk of spontaneous abortion for women working in all of the production plants with frequent exposure to petrochemicals (8.8% range of 5.8%-9.8%) compared with those working in nonchemical plants (2.2% range of 0.0%-7.1%). Also, when a comparison was made between exposed and non-exposed groups within each plant, exposure to petrochemicals was consistently associated with an increased risk of spontaneous abortion. The overall odds ratio (OR) was 2.7 (95% confidence interval (95% CI) 1.8 to 3.9) after adjusting for potential confounders. When the analysis was performed with the exposure information obtained from the women' interview responses for (self reported) exposures, the estimated OR for spontaneous abortions was 2.9 (95% CI 2.0 to 4.0). The analysis was repeated by excluding those 452 women who provided inconsistent reports between recalled exposure and work history, and a comparable risk of spontaneous abortion (OR 2.9 95% CI 2.0 to 4.4) was found. In analyses for exposure to specific chemicals, an increased risk of spontaneous abortion was found with exposure to most chemicals, and the results for benzene (OR 2.5 95% CI 1.7 to 3.7), gasoline (OR 1.8 95% CI 1.1 to 2.9), and hydrogen sulphide (OR 2.3 95% CI 1.2 to 4.4) were significant. An increased risk of spontaneous abortion was found associated with the exposure to petrochemicals, including benzene, gasoline, and hydrogen sulphide.
Publisher: Oxford University Press (OUP)
Date: 06-2006
Publisher: Wiley
Date: 08-1994
DOI: 10.1111/J.1539-6924.1994.TB00276.X
Abstract: We review approaches to dose-response modeling and risk assessment for binary data from developmental toxicity studies. In particular, we focus on jointly modeling fetal death and malformation and use a continuation ratio formulation of the multinomial distribution to provide a model for risk. Generalized estimating equations are used to account for clustering of animals within litters. The fitted model is then used to calculate doses corresponding to a specified level of excess risk. Two methods of arriving at a lower confidence limit or Benchmark dose are illustrated and compared. We also discuss models based on single binary end points and compare our approach to a binary analysis of whether or not the animal was 'affected' (either dead or malformed). The models are illustrated using data from four developmental toxicity studies in EG, DEHP, TGDM, and DYME conducted through the National Toxicology Program.
Publisher: Wiley
Date: 03-12-2008
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2006
Publisher: Oxford University Press (OUP)
Date: 03-1990
Publisher: Wiley
Date: 1991
Abstract: Mortality related to causes other than the treated disease may have a significant impact on overall survival in long-term clinical trials. We present a model that adjusts for age-related competing mortality when cause of death is missing or only partially available. Through use of a piecewise exponential survival model, we extend relative survival methods to continuous follow-up data, allowing the competing mortality to differ from that of the general population by a scale parameter. An EM algorithm provides a simple way to compute the maximum likelihood estimators (MLEs) and to test hypotheses using widely available software. We compare the bias and relative efficiency of this model to a piecewise exponential Cox model for overall survival. Theoretical results are confirmed by simulations and illustrated with data from a clinical trial in colorectal cancer. This ex le also shows how age-related and disease-related mortality can be confounded in an analysis of overall survival. We conclude with a discussion of the advantages and disadvantages of the model.
Publisher: Institute of Mathematical Statistics
Date: 06-1989
Publisher: Wiley
Date: 06-2006
Publisher: MDPI AG
Date: 03-02-2017
Publisher: Wiley
Date: 25-03-2018
Abstract: Spatial models for disease mapping should ideally account for covariates measured both at in idual and area levels. The newly available "indiCAR" model fits the popular conditional autoregresssive (CAR) model by accommodating both in idual and group level covariates while adjusting for spatial correlation in the disease rates. This algorithm has been shown to be effective but assumes log-linear associations between in idual level covariates and outcome. In many studies, the relationship between in idual level covariates and the outcome may be non-log-linear, and methods to track such nonlinearity between in idual level covariate and outcome in spatial regression modeling are not well developed. In this paper, we propose a new algorithm, smooth-indiCAR, to fit an extension to the popular conditional autoregresssive model that can accommodate both linear and nonlinear in idual level covariate effects while adjusting for group level covariates and spatial correlation in the disease rates. In this formulation, the effect of a continuous in idual level covariate is accommodated via penalized splines. We describe a two-step estimation procedure to obtain reliable estimates of in idual and group level covariate effects where both in idual and group level covariate effects are estimated separately. This distributed computing framework enhances its application in the Big Data domain with a large number of in idual/group level covariates. We evaluate the performance of smooth-indiCAR through simulation. Our results indicate that the smooth-indiCAR method provides reliable estimates of all regression and random effect parameters. We illustrate our proposed methodology with an analysis of data on neutropenia admissions in New South Wales (NSW), Australia.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-1989
Publisher: Springer Science and Business Media LLC
Date: 09-2003
Publisher: Wiley
Date: 09-10-2014
DOI: 10.1002/ENV.2305
Publisher: Springer Science and Business Media LLC
Date: 22-09-2008
Abstract: A modest number of prospective studies of the composition of the intestinal microbiota and eczema in early life have yielded conflicting results. To examine the relationship between the bacterial ersity of the gut and the development of eczema in early life by methods other than stool culture. Fecal s les were collected from 21 infants at 1 and 4 months of life. Nine infants were diagnosed with eczema by the age of 6 months (cases) and 12 infants were not (controls). After conducting denaturating gradient gel electrophoresis (DGGE) of stool s les, we compared the microbial ersity of cases and controls using the number of electrophoretic bands and the Shannon index of ersity ( H' ) as indicators. Control subjects had significantly greater fecal microbial ersity than children with eczema at ages 1 (mean H' for controls = 0.75 vs. 0.53 for cases, P = 0.01) and 4 months (mean H' for controls = 0.92 vs. 0.59 for cases, P = 0.02). The increase in ersity from 1 to 4 months of age was significant in controls (P = 0.04) but not in children who developed eczema by 6 months of age (P = 0.32). Our findings suggest that reduced microbial ersity is associated with the development of eczema in early life.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2006
Publisher: Informa UK Limited
Date: 07-1999
Abstract: The authors examined the association between the risk of spontaneous abortion and the type of drinking water source in a rural Chinese population. Information about pregnancy outcomes and various exposures was collected by means of a detailed interview questionnaire. 2,876 pregnancies occurring in 1989-1993 among 2,201 nonsmoking and non-alcohol-drinking women were analyzed by logistic regression. Generalized estimating equations were used to adjust for correlations between multiple pregnancies in the same woman. The use of pond water as a drinking water source was associated with a higher risk of spontaneous abortion than the use of well or river water (odds ratio, 1.63 95% confidence interval, 1.11 to 2.39), adjusting for potential confounders. More studies are needed to identify the agents responsible for the observed association. The results of this study emphasize the importance of monitoring potential drinking-water contamination in communities.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2000
DOI: 10.1097/00043764-200010000-00004
Abstract: This study investigated the association between occupational pesticide exposure and semen quality among Chinese workers. Male workers, 32 who were exposed to organophosphate pesticides and 43 who were not exposed were recruited from two nearby factories and interviewed. Following a work shift, semen and urine s les were collected for pesticide metabolite analysis. Semen s les were analyzed for sperm concentration, percentage of motility, and percentage of normal structure. Within the exposed group, the mean end-of-shift urinary p-nitrophenol levels were 0.22 and 0.15 mg/L for the high- and low-exposure subgroups, respectively. Linear regression analysis of in idual semen parameters revealed a significant reduction of sperm concentration (35.9 x 10(6) vs 62.8 x 10(6), p < 0.01) and percentage of motility (47% vs 57%, p = 0.03) but not percentage of sperm with normal structure (57% vs 61%, p = 0.13). Multivariate modeling showed a significant overall shift in the mean semen parameter. Occupational exposure to ethylparathion and methamidophos seems to have a moderately adverse effect on semen quality.
Publisher: Elsevier BV
Date: 11-2002
Abstract: It has been postulated that exposure to bacterial endotoxins and animals early in life might confer protection against the development of asthma and allergies. We investigated the longitudinal effects of exposure to house dust endotoxin (HDE), allergen levels, and the presence of a dog in the home on wheezing in young children over a 4-year period. Two hundred twenty-six children younger than 5 years were followed for 4 years. Endotoxin and allergen levels were measured from house dust collected at baseline. Longitudinal associations were investigated by using a proportional hazards technique that allowed for multiple outcomes per subject. Exposure to high concentrations of HDE of greater than the median level was associated with an increased risk for wheezing over the period of observation (multivariate relative risk, 1.52 95 % CI, 1.07-2.14), but this risk rapidly decreased over time (P for trend =.005). Exposure to cockroach allergen was associated with increased risk for wheezing, whereas exposure to cat allergen and the presence of a dog in the home were both associated with decreased risk for wheezing. The risks associated with cockroach allergen, cat allergen, and dog did not change over the period of observation. The negative associations between exposures to dogs and cat allergen and wheeze appear to be independent of the effects of endotoxin and suggest that separate mechanisms might mediate the effects of HDE exposure and pet exposure on the developing immune system.
Publisher: American Thoracic Society
Date: 05-2003
Publisher: Informa UK Limited
Date: 03-2000
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2001
DOI: 10.1097/00043764-200106000-00012
Abstract: To investigate the association between organic solvent exposure and menstrual disturbance, we conducted a cross-sectional study among 1408 petrochemical workers in China. Based on an industrial hygiene evaluation, we classified the workshops according to the presence or absence of organic solvents (benzene, styrene, toluene, or xylene). We used logistic regression to estimate odds ratios and 95% confidence intervals for prolonged menstrual cycle length (oligomenorrhea: average cycle length > 35 days during the previous year) associated with the exposure. After adjustment for confounders, each additional year of work in an exposed workshop was associated with a 7% increase in oligomenorrhea (odds ratio, 1.07 95% confidence interval, 1.00 to 1.14). Compared with no exposure, 3 or more years of exposure was associated with a 53% increase in oligomenorrhea (odds ratio, 1.53 95% confidence interval, 1.00 to 2.34). We concluded that exposure to organic solvents is associated with a trend toward increased frequency of oligomenorrhea.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Wiley
Date: 04-1999
DOI: 10.1002/(SICI)1097-0274(199904)35:4<321::AID-AJIM1>3.0.CO;2-L
Abstract: To evaluate the relationship between long-term exposure to cotton dust and Gram-negative bacterial endotoxin on lung function, we conducted an 11-year follow-up study of cotton textile workers in Shanghai, China. Workers at a nearby silk-thread manufacturing mill were used as a referent population. Ninety percent of the original cohort of 445 cotton and 467 silk textile workers--both active and retired--were identified for testing in the 11th year. Questionnaires and spirometric testing were performed, as well as cotton dust and endotoxin s ling at three points over the 11-year follow-up period: at baseline, at Year 5, and at Year 11. After excluding deaths and subjects on sick-leave, 84% of the original cohort had complete health and environmental data. The data were reanalyzed using generalized estimating equations feedback model which allow for subject transfer over time between work areas, various exposure levels to dust and endotoxin, and FEV1. Cotton workers had a larger loss of FEV1 during the first 5 years of study (-40 mls/yr) as compared with the second 6 years of follow-up (-18 mls/yr). During the same periods, the average decline among silk workers was slightly higher in the first period, but was more consistent (-30 mls/yr vs. -27 mls/yr), and these differences could not be explained by worker selection or dropout. When cumulative exposure to dust and endotoxin were estimated and used in a multivariate model (GEE) for FEV1 loss, cumulative dust, but not endotoxin, was associated with 11-year loss in FEV1 after adjustments for confounders. There was evidence of feedback between dust-exposure levels and FEV1, indicating the existence of a healthy-worker survivor effect. After accounting for a healthy-worker survivor effect, we found a significant relationship between dust exposure and FEV1 decline. Our results suggest that cotton dust is more strongly associated with chronic airflow limitation than associated endotoxins. Further work is needed to clarify potential reversibility after cessation of exposure, and the relative contributions of dust, endotoxin, and tobacco to chronic respiratory impairment in cotton and other vegetable-exposed workers.
Publisher: Wiley
Date: 07-2000
DOI: 10.1002/1521-4036(200007)42:3<279::AID-BIMJ279>3.0.CO;2-F
Publisher: JSTOR
Date: 12-1996
DOI: 10.2307/2532862
Publisher: Wiley
Date: 03-1999
DOI: 10.1111/J.0006-341X.1999.00238.X
Abstract: We propose a smooth hazard estimator for interval-censored survival data using the method of local likelihood. The model is fit using a local EM algorithm. The estimator is more descriptive than traditional empirical estimates in regions of concentrated information and takes on a parametric flavor in regions of sparse information. We derive two different standard error estimates for the smooth curve, one based on asymptotic theory and the other on the bootstrap. We illustrate the local EM method for times to breast cosmesis deterioration (Finkelstein, 1986, Biometrics 42, 845-854) and for times to HIV-1 infection for in iduals with hemophilia (Kroner et al., 1994, Journal of AIDS 7, 279-286). Our hazard estimates for each of these data sets show interesting structures that would not be found using a standard parametric hazard model or empirical survivorship estimates.
Publisher: Springer Science and Business Media LLC
Date: 04-2004
Publisher: JSTOR
Date: 12-1996
DOI: 10.2307/2532865
Publisher: Environmental Health Perspectives
Date: 07-2006
DOI: 10.1289/EHP.8827
Abstract: We assessed determinants of cord serum polychlorinated biphenyl (PCB) levels among 720 infants born between 1993 and 1998 to mothers living near a PCB-contaminated Superfund site in Massachusetts, measuring the sum of 51 PCB congeners (capital sigmaPCB) and ascertaining maternal address, diet, sociodemographics, and exposure risk factors. Addresses were geocoded to obtain distance to the Superfund site and neighborhood characteristics. We modeled log10(capital sigmaPCB) as a function of potential in idual and neighborhood risk factors, mapping model residuals to assess spatial correlates of PCB exposure. Similar analyses were performed for light (mono-tetra) and heavy (penta-deca) PCBs to assess potential differences in exposure pathways as a function of relative volatility. PCB-118 (relatively prevalent in site sediments and cord serum) was assessed separately. The geometric mean of capital sigmaPCB levels was 0.40 (range, 0.068-18.14) ng/g serum. Maternal age and birthplace were the strongest predictors of capital sigmaPCB levels. Maternal consumption of organ meat and local dairy products was associated with higher and smoking and previous lactation with lower capital sigmaPCB levels. Infants born later in the study had lower capital sigmaPCB levels, likely due to temporal declines in exposure and site remediation in 1994-1995. No association was found between capital sigmaPCB levels and residential distance from the Superfund site. Similar results were found with light and heavy PCBs and PCB-118. Previously reported demographic (age) and other (lactation, smoking, diet) correlates of PCB exposure, as well as local factors (consumption of local dairy products and Superfund site dredging) but not residential proximity to the site, were important determinants of cord serum PCB levels in the study community.
Publisher: Oxford University Press (OUP)
Date: 12-2006
Publisher: Wiley
Date: 23-12-2020
DOI: 10.1002/SIM.8824
Publisher: Elsevier BV
Date: 2020
DOI: 10.2139/SSRN.3673629
Publisher: Wiley
Date: 07-1987
Abstract: The Mantel-Haenszel test provides a straightforward method to combine results from several clinical trials when only summary information, such as the proportion of deaths, is available for each trial. More efficient tests, such as the stratified logrank test, should be used if the survival and censoring times are known for all in iduals, but in practice, the cost and effort of obtaining this information may be prohibitive. The purpose of this paper is to derive a general expression for the asymptotic relative efficiency (ARE) of the Mantel-Haenszel test with respect to the stratified logrank test, and to compute the ARE in situations which are likely to be of practical interest. The results show that under realistic assumptions about the survival distribution, losses to follow-up and duration of accrual, the ARE frequently exceeds 80 per cent. An ex le is given to show the usefulness of the approach when combining proportions of deaths from several cancer clinical trials.
Publisher: JSTOR
Date: 03-1992
DOI: 10.2307/2532747
Publisher: Oxford University Press (OUP)
Date: 15-10-2000
Abstract: This study investigated whether the association between low level benzene exposure and shortened gestation is modified by two susceptibility genes, CYP1A1 and GSTT1. This report includes 542 (302 nonexposed, 240 benzene-exposed) nonsmoking and nondrinking mothers of singleton live births at Beijing Yanshan Petrochemical Corporation between June 1995 and June 1997. Epidemiologic and clinical data and blood s les were obtained from mothers. Multiple linear regression models were used to estimate the associations of benzene exposure and genetic susceptibility with gestational age, adjusting for maternal age, education, parity, stress, passive smoking, prepregnancy weight and height, and infant's sex. Without consideration of genotype, benzene exposure was associated with a decrease in mean gestational age of 0.29 (standard error (SE), 0.12) week. When stratified by the maternal CYP1A1 genotype, the estimated decrease was 0.54 (SE, 0.12) week for the AA group, which was significantly greater (p = 0.003) than that for the Aa/aa group, which showed no decrease in gestational age. When both CYP1A1 and GSTT1 were considered, the greatest decrease was found among exposed mothers with the CYP1A1 AA-GSTT1 absent group (0.79 (SE, 0.25) week) and the CYP1A1 AA-GSTT1 present group (0.50 (SE, 0.22) week). Among the nonexposed, genetic susceptibility alone did not confer a significant adverse effect. This study provides evidence of gene-environment interaction and supports further assessment of the role of genetic susceptibility in the evaluation of reproductive toxins.
Publisher: Wiley
Date: 05-1999
DOI: 10.1002/(SICI)1099-095X(199905/06)10:3<279::AID-ENV352>3.0.CO;2-X
Publisher: Archives of Pathology and Laboratory Medicine
Date: 06-1999
DOI: 10.5858/1999-123-0524-MAOPFO
Abstract: Objective.—Hepatocellular carcinoma is a malignancy found worldwide that has typically poor prognosis despite treatment. Although several studies have dealt with prognostic factors, just a few detailed analyses of large series correlating the pathology of hepatocellular carcinoma with prognosis are available. The present study was undertaken to address this limitation. Patients and Methods.—Our prior clinical study described 432 patients, but sufficient tissue was available for evaluation in only 299 patients. Of these, 224 s les contained primary hepatocellular carcinoma, while the remainder contained only metastatic tumor. Characteristics evaluated included degree of tumor differentiation, associated cirrhosis or hepatitis, presence of cytoplasmic inclusion bodies, and blood vessel invasion by the neoplasm. Results.—Of the 224 patients, 71% were male, 65% white, and 73% over the age of 45 years. Ninety-one percent were from North America. A total of 42 patients were found to have cirrhosis. Thirty-five percent had cytoplasmic inclusion bodies, and 25% showed evidence of blood vessel invasion. Tumor response rates (tumor shrinkage) were low (8%) regardless of treatment. Presence of cytoplasmic eosinophilic inclusion bodies and blood vessel invasion were not associated with increased survival. Some histopathologies (pelioid, spindle cell, fibrolamellar) were associated with a better prognosis. Patients with a predominant trabecular pattern (43%) did particularly poorly. Although sex was significantly associated with survival using a univariate analysis, this effect disappeared in a multivariate Cox model that adjusted simultaneously for other factors. Conclusion.—This investigation suggests that histologic subtype and clinical features may provide useful prognostic information in hepatocellular carcinoma. Poorer survival was observed in males, older patients with poorly differentiated tumors, or when associated with cirrhosis. Age younger than 45 years was a good prognostic factor, and presence of cirrhosis had an adverse effect on survival.
Publisher: Environmental Health Perspectives
Date: 2008
DOI: 10.1289/EHP.9955
Publisher: Human Kinetics
Date: 10-2005
DOI: 10.1123/JPAH.2.4.397
Abstract: Limited data address psychosocial and environmental correlates of physical activity. We assessed associations of regular and recent leisure-time physical activity with physical/mental well-being, social support, and civic trust and reciprocity in a working-class Boston neighborhood. We surveyed 409 adults in 1999 to 2000 using methodology from the Behavioral Risk Factor Surveillance System. Adjusted for demographic variables, correlates of regular physical activity included feeling energetic/healthy (odds ratio [OR] = 1.7, 95% confidence interval [CI] 1.3 to 2.3 for each one of four categories), feeling worried/tense/anxious (OR = 0.7, 95% CI 0.5 to 1.0), pain interfering with usual activities (OR = 0.5, 95% CI 0.3 to 0.8), feeling sad/blue/depressed (OR = 0.7, 95% CI, 0.5 to 0.9), inadequate sleep/rest (OR = 0.8, 95% CI 0.6 to 1.0) and feeling satisfied with life (OR = 1.6, 95% CI 1.0 to 2.6, for very satisfied versus other). We found similar associations for participation in any physical activity. Lack of energy, anxiety, pain, sadness, poor sleep, and dissatisfaction with life were associated with low physical activity levels.
Publisher: Oxford University Press (OUP)
Date: 06-03-2015
Publisher: Springer Science and Business Media LLC
Date: 2000
Publisher: Institute of Mathematical Statistics
Date: 11-2015
DOI: 10.1214/15-STS528
Publisher: Springer Science and Business Media LLC
Date: 2007
Publisher: SAGE Publications
Date: 04-2000
Publisher: Environmental Health Perspectives
Date: 03-2007
DOI: 10.1289/EHP.9152
Publisher: Wiley
Date: 08-12-2013
DOI: 10.1002/SIM.6050
Publisher: Wiley
Date: 30-10-1996
DOI: 10.1002/(SICI)1097-0258(19961030)15:20<2191::AID-SIM358>3.0.CO;2-D
Abstract: Methylmercury (MeHg), a long-lasting organic pollutant, is known to induce cytotoxic effects in mammalian cells. Epidemiological studies have suggested that environmental exposure to MeHg is linked to the development of diabetes mellitus (DM). The exact molecular mechanism of MeHg-induced pancreatic β-cell cytotoxicity is still unclear. Here, we found that MeHg (1-4 μM) significantly decreased insulin secretion and cell viability in pancreatic β-cell-derived RIN-m5F cells. A concomitant elevation of mitochondrial-dependent apoptotic events was observed, including decreased mitochondrial membrane potential and increased proapoptotic (
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.AUEC.2018.12.003
Abstract: Unplanned return visits account for up to 5% of Emergency Department presentations in Australia and have been associated with adverse events and increased costs. A large number of studies examine the incidence, characteristics and outcomes of unplanned return visits but few studies examine the reasons for return from a patient perspective. The objective of this integrative review was to determine the incidence, characteristics, outcomes and reasons for unplanned return visits to Emergency Departments. An integrative literature review design was employed to conduct a structured search of the literature using the databases CINAHL, MEDLINE, PubMed, ProQuest and EMBASE (inception to June 2018). Results were screened using predefined criteria and final studies collated and appraised using a quality assessment tool. Fifty-two primary research articles were included in the review. The timeframe used to capture unplanned return visits varied and the incidence ranged between 0.07% and 33%. The majority of patients who return unplanned to the Emergency Department are subsequently discharged (51% and 90%) without an adverse event. There is no consensus on the timeframe employed to classify unplanned return visits to the Emergency Department and the commonly used 72h lacks evidence. Routine statewide data linkage to capture return visits to other facilities is needed to ensure accurate data about this vulnerable patient group. Further research that focuses on patient and clinician perspectives is required to facilitate the development of local strategies to reduce the incidence of avoidable unplanned return visits.
Publisher: Elsevier BV
Date: 09-1998
DOI: 10.1016/S0360-3016(98)00232-6
Abstract: Squamous carcinoma of the thoracic esophagus has an extremely poor prognosis. This study, EST-1282, was undertaken by the Eastern Cooperative Oncology Group (ECOG) to determine whether the combined use of 5-fluorouracil (5-FU), mitomycin C, and radiation therapy improved the disease-free survival and overall survival of patients with carcinoma of the esophagus, compared to those who received radiation therapy alone. Two- and 5-year survivals were 12% and 7% in the radiation alone arm and 27% and 9% in the chemoradiation arm. Patients treated with chemoradiation had a longer median survival (14.8 months), compared to patients receiving radiation therapy alone (9.2 months). This difference was statistically significant. The same pattern of survival was noted in almost all subgroups independent of whether surgical resection was performed.
Publisher: Wiley
Date: 12-2000
DOI: 10.1111/J.0006-341X.2000.01268.X
Abstract: In this article, we present an estimation approach for solving nonlinear constrained generalized estimating equations that can be implemented using object-oriented software for nonlinear programming, such as nlminb in Splus or fmincon and lsqnonlin in Matlab. We show how standard estimating equation theory includes this method as a special case so that our estimates, when unconstrained, will remain consistent and asymptotically normal. To illustrate this method, we fit a nonlinear dose-response model with nonnegative mixed bound constraints to clustered binary data from a developmental toxicity study. Satisfactory confidence intervals are found using a nonparametric bootstrap method when a common correlation coefficient is assumed for all the dose groups and for some of the dose-specific groups.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2005
Publisher: Wiley
Date: 10-1990
Abstract: In an effort to ease staffing burdens and potentially improve patient outcome in an intensive care unit (ICU) environment, we are developing a real-time system to accurately and efficiently diagnose cardiopulmonary emergencies. The system is being designed to utilize all relevant routinely-monitored physiological data in order to automatically diagnose potentially fatal events. The initial stage of this project involved formulating the overall system design and appropriate methods for real-time data acquisition, data storage, data trending, waveform analysis, and implementing diagnostic rules. Initially, we defined a conceptual analysis of the minimum physiologic data set, and the monitoring time-frames (trends) which would be required to diagnose cardiopulmonary emergencies. Following that analysis, we used a fuzzy logic diagnostic engine to analyze physiological data during a simulated arrhythmic cardiac arrest (ACA) in order to assess the validity of our diagnostic methodology. We used rate, trend, and morphologic data extracted from the following signals: expired CO2 time-concentration curve (capnogram), electrocardiogram, and arterial blood pressure. The system performed well: The fuzzy logic engine effectively diagnosed the likelihood of ACA from the subtle hemodynamic trends which preceded the complete arrest. As the clinical picture worsened, the fuzzy logic-based system accurately indicated the change in patient condition. Termination of the simulated arrest was rapidly detected by the diagnostic engine. In view of the effectiveness of this fuzzy logic implementation, we plan to develop additional fuzzy logic modules to diagnose other cardiopulmonary emergencies.
Publisher: Wiley
Date: 11-05-2016
DOI: 10.1111/VOX.12407
Abstract: Vein visualization technology (VVT) devices use near-infrared light to assist location of peripheral veins. The current study investigated the impact of VVT on donor experience and collection success for young blood donors at the Australian Red Cross Blood Service. The study in donors aged 18 to 30 years used a two intervention to one control randomized trial design with 285 new and 587 returning donors recruited at two sites. Donors reported presyncopal symptoms, phlebotomy pain, anxiety and intentions to redonate along with other measures. Participating phlebotomists rated usefulness of the technology. Flow rates, collection volumes and other donation information were taken from routine data. No significant differences were found between control and intervention groups on presyncopal symptoms, phlebotomy pain, anxiety, intentions to redonate, flow rates, collection volumes or vasovagal reactions (all P's > 0·05). Phlebotomist ratings of VVT were significantly more positive when they had less than 5 years of experience (P < 0·01) or when the vein was not visible to the naked eye (P < 0·01). Results suggest that VVT does not improve the donation experience for younger blood donors. Staff reports indicate that VVT may have some utility for assisting with difficult phlebotomies.
Publisher: Informa UK Limited
Date: 09-1989
Publisher: Elsevier BV
Date: 2007
DOI: 10.1016/J.JACI.2006.09.012
Abstract: The relation between respiratory illnesses in early life and the development of asthma and atopy in childhood is incompletely understood. We sought to examine the relationship between respiratory illnesses in early life and atopic diseases at school age. We performed a prospective birth cohort study of the relationship between respiratory illnesses in the first year of life and asthma, atopy (sensitization to >or=1 allergen), and allergic rhinitis at school age in 440 children with a parental history of atopy. Logistic regression was used to examine the relationship between respiratory illnesses and asthma, atopy, and allergic rhinitis. The relationship between respiratory illnesses in early life and repeated measures of wheezing between the ages of 1 and 7 years was investigated by using a proportional hazards models. Physician-diagnosed croup (adjusted odds ratio [OR], 0.30 95% CI, 0.12-0.72) and having 2 or more physician-diagnosed ear infections (adjusted OR, 0.58 95% CI, 0.35-0.98) in the first year of life were inversely associated with atopy at school age. Physician-diagnosed bronchiolitis before age 1 year was significantly associated with asthma at age 7 years (adjusted OR, 2.77 95% CI, 1.23-6.22). Recurrent nasal catarrh (>or=3 episodes of a runny nose) in the first year of life was associated with allergic rhinitis at age 7 years (adjusted OR, 2.99 95% CI, 1.03-8.67). The relationship between early-life respiratory illnesses and asthma and atopy is complex and likely dependent on the type of infection and immune response it initiates. Certain respiratory illnesses in early life modify the risk of atopy and asthma at school age.
Publisher: Springer Science and Business Media LLC
Date: 20-04-2010
Publisher: Wiley
Date: 03-2009
DOI: 10.1111/J.1541-0420.2008.01022.X
Abstract: Classical diagnostics for structural equation models are based on aggregate forms of the data and are ill suited for checking distributional or linearity assumptions. We extend recently developed goodness-of-fit tests for correlated data based on subject-specific residuals to structural equation models with latent variables. The proposed tests lend themselves to graphical displays and are designed to detect misspecified distributional or linearity assumptions. To complement graphical displays, test statistics are defined the null distributions of the test statistics are approximated using computationally efficient simulation techniques. The properties of the proposed tests are examined via simulation studies. We illustrate the methods using data from a study of in utero lead exposure.
Publisher: Informa UK Limited
Date: 03-07-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2006
Publisher: Informa UK Limited
Date: 05-2002
DOI: 10.1080/00039890209602938
Abstract: The authors investigated the association of birth weight with maternal and paternal exposure to organic solvents in 1,222 couples employed in a large petrochemical corporation in Beijing, China, during the period between 1994 and 1998. A trained interviewer assessed parental exposures to organic solvents. The authors used generalized additive models to examine the association between birth weight and parental exposure to organic solvents. After the authors adjusted for potential confounders, maternal exposure to solvents was significantly associated with reduced birth weight (-81.7 gm, 95% confidence interval = -106.3, -3.1), and reduced birth weights of female babies and of younger mothers' babies were statistically significant. Maternal exposure to organic solvents was associated with reduced birth weight in this population, but paternal exposure to organic solvents was not similarly associated.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2005
Publisher: Informa UK Limited
Date: 12-2007
Publisher: Elsevier BV
Date: 09-2002
Publisher: Informa UK Limited
Date: 12-2006
Publisher: American Diabetes Association
Date: 12-2001
DOI: 10.2337/DIABETES.50.12.2842
Abstract: Cigarette smoking and poor glycemic control are risk factors for diabetic nephropathy in type 1 diabetes. However, the specifics of the relation of these risk factors to the onset of this complication have not been elucidated. To investigate these issues, we followed for 4 years 943 Joslin Clinic patients aged 15–44 years with type 1 diabetes who had normoalbuminuria during the 2-year baseline period. Microalbuminuria developed in 109 of the 943 in iduals, giving an incidence rate of 3.3/100 person-years. The risk of onset of microalbuminuria was predicted somewhat more precisely by the measurements during the 1st and 2nd years preceding onset than by all the measurements during the longer (4-year) interval, suggesting attenuation of the impact of past hyperglycemia over time. Point estimates of the incidence rate (per 100 person-years) according to quartiles of HbA1c during the 1st and 2nd years preceding the outcome were 1.3 in the 1st, 1.5 in the 2nd, 3.1 in the 3rd, and 6.9 in the 4th (P = 1.3 × 10−9). Point estimates of the incidence rate (per 100 person-years) according to smoking status were 7.9 for current smokers, 1.8 for past smokers, and 2.2 for those who had never smoked (P = 2.0 × 10−7). In a multiple logistic model, the independent effects of HbA1c level and cigarette smoking remained highly significant, but their magnitudes were reduced. Using the same covariates in a generalized additive model, we examined the shape of the relationship between HbA1c and onset of microalbuminuria and found significant nonlinearity in the logarithm of odds scale (P = 0.04). The slope was steeper with HbA1c & % than & %. Furthermore, the change in the slope was magnified among current smokers. In conclusion, patients with type 1 diabetes who smoke and have an HbA1c & % have the highest risk of onset of microalbuminuria.
Publisher: JSTOR
Date: 11-2000
DOI: 10.2307/3434958
Publisher: American Society of Clinical Oncology (ASCO)
Date: 05-2001
DOI: 10.1200/JCO.2001.19.9.2413
Abstract: PURPOSE: To investigate mechanism-directed regimens in maximizing the efficacy of fluorouracil (5-FU) in advanced colorected cancer. PATIENTS AND METHODS: Based on promising phase II data, a randomized comparison of various methods for the biochemical modulation of 5-FU was undertaken in patients with advanced colorectal cancer. The control group received single-agent 5-FU as a 24-hour infusion weekly. Patients (N = 1,120) with no prior chemotherapy for metastatic disease were randomized to one of the following arms: arm A, 5-FU 2,600 mg/m 2 by 24-hour infusion, weekly arm B, N-phosphonoacetyl-l-aspartic acid 250 mg/m 2 day l, 5-FU 2,600 mg/m 2 by 24-hour infusion day 2, weekly arm C, 5-FU 600 mg/m 2 with oral leucovorin (LV) 125 mg/m 2 hourly for the preceding 4 hours, weekly arm D, 5-FU 600 mg/m 2 with intravenous (IV) LV 600 mg/m 2 , weekly arm E, 5-FU 750 mg/m 2 /d IV by continuous infusion for 5 days, then 750 mg/m 2 weekly, and recombinant interferon alfa-2a 9 million units subcutaneously three times weekly. Median follow-up was 4.8 years. RESULTS: Of the 1,098 assessable patients, 57% had measurable disease. The toxicity of all the regimens was tolerable. Grade 4 or worse toxicity occurred in 11%, 11%, 30%, 24%, and 22% on each arm, respectively diarrhea was the most common adverse effect. These toxicity patterns favored significantly (P .001) the 24-hour infusion arms. Median survival (months) by arm was A, 14.8 B, 11.9 C, 13.5 D, 13.6 and E, 15.2. These survival durations did not differ significantly. CONCLUSION: We conclude that a weekly infusion regimen of 5-FU is significantly less toxic than and as effective as 5-FU bolus regimens modulated by either LV or interferon in patients with metastatic colorectal cancer.
Publisher: Informa UK Limited
Date: 04-2003
DOI: 10.1080/10473289.2003.10466174
Abstract: The need to assess correlation in settings where multiple measurements are available on each of the variables of interest often arises in environmental science. However, this topic is not covered in introductory statistics texts. Although several ad hoc approaches can be used, they can easily lead to invalid conclusions and to a difficult choice of an appropriate measure of the correlation. Lam et al. approached this problem by using maximum likelihood estimation in cases where the replicate measurements are linked over time, but the method requires specialized software. We reanalyze the data of Lam et al. using PROC MIXED in SAS and show how to obtain the parameter estimates of interest with just a few lines of code. We then extend Lam et al.'s method to settings where the replicate measurements are not linked. Analysis of the unlinked case is illustrated with data from a study designed to assess correlations between indoor and outdoor measurements of benzene concentration in the air.
Publisher: Wiley
Date: 2000
DOI: 10.1002/1096-9926(200012)62:6<406::AID-TERA7>3.0.CO;2-E
Publisher: American Thoracic Society
Date: 15-07-2003
Start Date: 2015
End Date: End date not available
Funder: Bill and Melinda Gates Foundation
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