ORCID Profile
0000-0001-6011-6951
Current Organisations
Institute of Tropical Medicine Antwerp
,
Hôpital Erasme
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Publisher: SAGE Publications
Date: 08-09-2009
Abstract: Background Clinical research in trauma patients poses multiple challenges in study design. These reflect the heterogeneity of injury and treatment, the paucity of acceptable study endpoints aside from mortality, and the difficulties inherent in obtaining informed consent in acutely ill populations. A current ex le of this problem is the study of recombinant factor VIIa (rFVIIa), which has attracted considerable interest as a systemic procoagulant agent for use in trauma patients with exsanguinating hemorrhage. Purpose To report on the implementation of an international trial — CONTROL — intended to assess the efficacy and safety of rFVIIa in trauma, and discuss trauma research study design in light of this experience. Methods The CONTROL trial international steering committee confronted a number of barriers in the design of the CONTROL trial. They addressed methodologies for (1) standardizing entry criteria for trauma patients suffering inherently heterogeneous injuries, (2) obtaining informed consent in an acutely injured population with altered levels of consciousness, (3) avoiding futile care, while recruiting subjects with incompletely diagnosed injuries, (4) standardizing trauma intensive care across different investigating sites and countries, and (5) establishing study endpoints that were both clinically relevant and convincing to regulatory authorities. The resulting study methodology is reported. Results The CONTROL trial began active recruitment in October 2005, and was halted on June 11, 2008 because the observed mortality in the 576 enrolled patients was so far below expectations that the study would lack sufficient statistical power at the planned number of subjects to demonstrate a benefit. The utility of the endpoints selected for study will not be known until completion of data analysis. Limitations Any clinical trial in trauma patients must cope with the urgency of care required, issues of patient heterogeneity, standardization of care across multiple centers, and the difficulties of obtaining informed consent. Conclusion Research in acutely hemorrhaging trauma patients presents numerous scientific and ethical challenges. The methodology of the CONTROL study is presented as an ex le of how some of these challenges can be approached and managed, and of the pitfalls that may arise. Clinical Trials 2009 6: 467—479. ctj.sagepub.com
Publisher: Elsevier BV
Date: 12-2014
DOI: 10.1016/J.JCRC.2014.08.004
Abstract: Life-sustaining treatment (LST) limitation for elderly patients is highly controversial. In that context, it is useful to evaluate the attitudes to LST in the elderly among experienced intensive care unit (ICU) physicians with different backgrounds and cultures. A panel of 22 international ICU physicians from 13 countries responded to a questionnaire related to withholding (WH) and withdrawing (WD) LST in elderly patients using a semi-Likert scale. Most experts disagree or strongly disagree (77%) that age should be used as the sole criterion for WH or WD LST, and almost all disagree (91%) that there should be a specific age for such decision making. However, the vast majority (91%) acknowledge that age should be an important consideration in conjunction with other factors. Disagreement for consideration of prioritizing the young over the old in normal ICU operations was reported in 68%, whereas in an emergency triage situation, disagreement dropped to 18%. There is a consensus among ICU physicians that age cannot be the sole criterion on which health care decisions should be made. In that perspective, it is important to provide data showing that outcome differences between elderly and nonelderly patients are partly related to decisions to forgo LSTs.
Publisher: American College of Physicians
Date: 18-11-2008
Publisher: American Thoracic Society
Date: 2019
Publisher: Springer Science and Business Media LLC
Date: 04-05-2021
DOI: 10.1186/S12916-021-01974-X
Abstract: During the millennium development goals period, reduction in under-five mortality (U5M) and increases in child health intervention coverage were characterised by sub-national disparities and inequities across Kenya. The contribution of changing risk factors and intervention coverage on the sub-national changes in U5M remains poorly defined. Sub-national county-level data on U5M and 43 factors known to be associated with U5M spanning 1993 and 2014 were assembled. Using a Bayesian ecological mixed-effects regression model, the relationships between U5M and significant intervention and infection risk ecological factors were quantified across 47 sub-national counties. The coefficients generated were used within a counterfactual framework to estimate U5M and under-five deaths averted (U5-DA) for every county and year (1993–2014) associated with changes in the coverage of interventions and disease infection prevalence relative to 1993. Nationally, the stagnation and increase in U5M in the 1990s were associated with rising human immunodeficiency virus (HIV) prevalence and reduced maternal autonomy while improvements after 2006 were associated with a decline in the prevalence of HIV and malaria, increase in access to better sanitation, fever treatment-seeking rates and maternal autonomy. Reduced stunting and increased coverage of early breastfeeding and institutional deliveries were associated with a smaller number of U5-DA compared to other factors while a reduction in high parity and fully immunised children were associated with under-five lives lost. Most of the U5-DA occurred after 2006 and varied spatially across counties. The highest number of U5-DA was recorded in western and coastal Kenya while northern Kenya recorded a lower number of U5-DA than western. Central Kenya had the lowest U5-DA. The deaths averted across the different regions were associated with a unique set of factors. Contributions of interventions and risk factors to changing U5M vary sub-nationally. This has important implications for targeting future interventions within decentralised health systems such as those operated in Kenya. Targeting specific factors where U5M has been high and intervention coverage poor would lead to the highest likelihood of sub-national attainment of sustainable development goal (SDG) 3.2 on U5M in Kenya.
Publisher: Springer Science and Business Media LLC
Date: 22-11-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2010
Publisher: Oxford University Press (OUP)
Date: 25-06-2013
DOI: 10.1093/JAC/DKT261
Abstract: Continuous infusion (CI) of high-dose vancomycin is often used to treat life-threatening infections caused by less-susceptible Gram-positive bacteria. However, this approach has not been well studied in patients on continuous renal replacement therapy (CRRT). The aim of this study was to evaluate the adequacy of a new CI vancomycin regimen in septic patients undergoing CRRT. In this prospective study we measured vancomycin concentrations obtained with a new CI regimen for CRRT, which included a loading dose of 35 mg/kg given over a 4 h period followed by a daily dose of 14 mg/kg. Vancomycin concentrations were measured: at the end of the loading dose (T1) 12 h after the onset of therapy (T2) and 24 h after the onset of therapy (T3). Drug concentrations (at T2 and T3) were considered adequate if between 20 and 30 mg/L. CRRT intensity was calculated as: dialysate rate (mL/kg/h) + ultrafiltration rate (mL/kg/h). Vancomycin population pharmacokinetics were calculated using non-linear mixed-effects modelling. We studied 32 patients who received median (IQR) loading and daily vancomycin doses of 2750 mg (2250-3150) and 1100 mg (975-1270), respectively. Drug concentrations were: T1, 44 mg/L (38-58) T2, 27 mg/L (24-31) and T3, 23 mg/L (19-31). Vancomycin concentrations were adequate in 22/32 patients (69%) at T2 and in 20/32 (63%) at T3. The two relevant covariates that significantly affected drug concentrations were body weight and CRRT intensity. This new vancomycin regimen allowed the rapid achievement of target drug concentrations in the majority of patients. CRRT intensity had an influence on vancomycin clearance.
Publisher: BMJ
Date: 04-2021
DOI: 10.1136/BMJGH-2020-004544
Abstract: To improve child survival, it is necessary to describe and understand the spatial and temporal variation of factors associated with child survival beyond national aggregates, anchored at decentralised health planning units. Therefore, we aimed to provide subnational estimates of factors associated with child survival while elucidating areas of progress, stagnation and decline in Kenya. Twenty household surveys and three population censuses conducted since 1989 were assembled and spatially aligned to 47 subnational Kenyan county boundaries. Bayesian spatio-temporal Gaussian process regression models accounting for inadequate s le size and spatio-temporal relatedness were fitted for 43 factors at county level between 1993 and 2014. Nationally, the coverage and prevalence were highly variable with 38 factors recording an improvement. The absolute percentage change (1993–2014) was heterogeneous ranging between 1% and 898%. At the county level, the estimates varied across space and over time with a majority showing improvements after 2008 which was preceded by a period of deterioration (late-1990 to early-2000). Counties in Northern Kenya were consistently observed to have lower coverage of interventions and remained disadvantaged in 2014 while areas around Central Kenya had and historically have had higher coverage across all intervention domains. Most factors in Western and South-East Kenya recorded moderate intervention coverage although having a high infection prevalence of both HIV and malaria. The heterogeneous estimates necessitates prioritisation of the marginalised counties to achieve health equity and improve child survival uniformly across the country. Efforts are required to narrow the gap between counties across all the drivers of child survival. The generated estimates will facilitate improved benchmarking and establish a baseline for monitoring child development goals at subnational level.
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.JTCVS.2015.07.051
Abstract: The aim of this study was to compare outcomes in patients undergoing cardiac surgery who are aged 60 years or more or less than 60 years after implementation of a restrictive or a liberal transfusion strategy. This is a substudy of the Transfusion Requirements After Cardiac Surgery (TRACS) randomized controlled trial. In this subgroup analysis, we separated patients into those aged 60 years or more (elderly) and those aged less than 60 years randomized to a restrictive or a liberal strategy of red blood cell transfusion. The primary outcome was a composite defined as a combination of 30-day all-cause mortality and severe morbidity. Of the 502 patients included in the Transfusion Requirements After Cardiac Surgery study, 260 (51.8%) were aged 60 years or more and 242 (48.2%) were aged less than 60 years and were included in this study. The primary end point occurred in 11.9% of patients in the liberal strategy group and 16.8% of patients in the restrictive strategy group (P = .254) for those aged 60 years or more and in 6.8% of patients in the liberal strategy group and 5.6% of patients in the restrictive strategy group for those aged less than 60 years (P = .714). However, in the older patients, cardiogenic shock was more frequent in patients in the restrictive transfusion group (12.8% vs 5.2%, P = .031). Thirty-day mortality, acute respiratory distress syndrome, and acute renal injury were similar in the restrictive and liberal transfusion groups in both age groups. Although there was no difference between groups regarding the primary outcome, a restrictive transfusion strategy may result in an increased rate of cardiogenic shock in elderly patients undergoing cardiac surgery compared with a more liberal strategy. Cardiovascular risk of anemia may be more harmful than the risk of blood transfusion in older patients.
Publisher: American Medical Association (AMA)
Date: 07-05-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2011
Publisher: Wiley
Date: 25-11-2013
DOI: 10.1111/JGS.12544
Abstract: To determine the effect of age on patterns of infection and on outcomes in in iduals with infection. Analysis of data from an international, observational, point‐prevalence study: E xtended P revalence of I nfection in I ntensive C are ( EPIC II ). Intensive care units ( ICU s N = 1,265) in 75 countries. All adults present in a participating ICU on May 8, 2007. In iduals with an infection were included and classified according to age (18–44, 45–64, 65–74, 75–84, ≥85). Demographic, physiological, bacteriological, and therapeutic data were collected on the day of the study. Outcome data were collected until hospital discharge or for 60 days. Of the 13,796 adults enrolled in EPIC II , 7,087 (51.4%) had an infection. Of these, 330 (4.7%) were aged 85 and older, 1,405 (19.8%) were 75 to 84, 1,713 (24.2%) were 65 to 74, 2,358 (33.3%) were 45 to 64, and 1,281 (18.1%) were 18 to 44. Severity of illness did not differ between groups. Those aged 85 and older had fewer bloodstream infections than those younger than 75, fewer central nervous system infections than those who were younger than 65, and more abdominal infections than those who were younger than 45. A microbiological diagnosis was established less frequently in participants aged 85 and older than in younger participants. Gram‐negative microorganisms were more frequently isolated in those aged 85 and older than in other groups. ICU and hospital mortality were significantly higher in participants aged 85 and older than in those who were younger than 65. A large proportion of in iduals in the ICU with infection are aged 65 and older. Patterns of infection, including site and type of microorganism, vary according to age. Being aged 85 and older was an independent risk factor for mortality in in iduals in the ICU with infection.
Publisher: Springer Science and Business Media LLC
Date: 2011
DOI: 10.1186/CC10438
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.JCRC.2016.06.001
Abstract: The role of the critical care specialist has been unequivocally established in the management of severely ill patients throughout the world. Data show that the presence of a critical care specialist in the intensive care unit (ICU) environment has reduced morbidity and mortality, improved patient safety, and reduced length of stay and costs. However, many ICUs across the world function as "open ICUs," in which patients may be admitted under a primary physician who has not been trained in critical care medicine. Although the concept of the ICU has gained widespread acceptance amongst medical professionals, hospital administrators and the general public recognition and the need for doctors specializing in intensive care medicine has lagged behind. The curriculum to ensure appropriate training around the world is erse but should ideally meet some minimum standards. The World Federation of Societies of Intensive and Critical Care Medicine has set up a task force to address issues concerning the training, functions, roles, and responsibilities of an ICU specialist.
Publisher: Wiley
Date: 22-07-2013
DOI: 10.1111/ECI.12123
Abstract: The objective of this study is to assess the impact of dysnatraemia on mortality among intensive care unit (ICU) patients in a large, international cohort. Analysis of the Extended Prevalence of Infection in Intensive Care (EPIC II) study, a 1-day (8 May 2007) worldwide multicenter, prospective point prevalence study. Hyponatraemia was categorized as mild (130-134 mM/L), moderate (125-129 mM/L) or severe ( 155 mM/L). Patients with normal serum sodium (135-145 mM/L) constituted the reference group. The main outcome was hospital mortality. Analysis was conducted separately for patients admitted on the study day (25.8%) and those already present on the ICU (74.2%). Serum sodium was measured in 13 276 of the 13 796 patients (96.2%). A total of 3815 patients (28.7%) had dysnatraemia: 12.9% with hyponatraemia and 15.8% with hypernatraemia. The prevalence of dysnatraemia was significantly greater in patients already present on the ICU prior to the study day than for those just admitted (13.1% vs. 12.3% for hyponatraemia and 17.1% vs. 12.1% for hypernatraemia, both P < 0.001). Hospital mortality rates were higher in patients with dysnatraemia than in those with normal sodium levels and were directly related to the severity of hypo- and hypernatraemia. This association between dysnatraemia and mortality was similar in infected and noninfected patients (P = 0.061). Dysnatraemia is more frequent during the ICU stay than on the day of admission. Dysnatraemia in the ICU - even mild - is an independent predictor of increased hospital mortality.
Publisher: Springer Science and Business Media LLC
Date: 16-01-2018
DOI: 10.1007/S00134-018-5055-6
Abstract: Owing to an oversight by the authors, Figure 2 in this article was not the version intended for publication. The correct Figure 2, reproduced here, features footnote symbols and Figure 2b includes three studies as described in the main text.
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.JCRC.2016.04.017
Abstract: End-of-life care in the intensive care unit (ICU) was identified as an objective in a series of Task Forces developed by the World Federation of Societies of Intensive and Critical Care Medicine Council in 2014. The objective was to develop a generic statement about current knowledge and to identify challenges relevant to the global community that may inform regional and local initiatives. An updated summary of published statements on end-of-life care in the ICU from national Societies is presented, highlighting commonalities and differences within and between international regions. The complexity of end-of-life care in the ICU, particularly relating to withholding and withdrawing life-sustaining treatment while ensuring the alleviation of suffering, within different ethical and cultural environments is recognized. Although no single statement can therefore be regarded as a criterion standard applicable to all countries and societies, the World Federation of Societies of Intensive and Critical Care Medicine endorses and encourages the role of Member Societies to lead the debate regarding end-of-life care in the ICU within each country and to take a leading role in developing national guidelines and recommendations within each country.
Publisher: American Medical Association (AMA)
Date: 02-12-2009
Abstract: Infection is a major cause of morbidity and mortality in intensive care units (ICUs) worldwide. However, relatively little information is available about the global epidemiology of such infections. To provide an up-to-date, international picture of the extent and patterns of infection in ICUs. The Extended Prevalence of Infection in Intensive Care (EPIC II) study, a 1-day, prospective, point prevalence study with follow-up conducted on May 8, 2007. Demographic, physiological, bacteriological, therapeutic, and outcome data were collected for 14,414 patients in 1265 participating ICUs from 75 countries on the study day. Analyses focused on the data from the 13,796 adult (>18 years) patients. On the day of the study, 7087 of 13,796 patients (51%) were considered infected 9084 (71%) were receiving antibiotics. The infection was of respiratory origin in 4503 (64%), and microbiological culture results were positive in 4947 (70%) of the infected patients 62% of the positive isolates were gram-negative organisms, 47% were gram-positive, and 19% were fungi. Patients who had longer ICU stays prior to the study day had higher rates of infection, especially infections due to resistant staphylococci, Acinetobacter, Pseudomonas species, and Candida species. The ICU mortality rate of infected patients was more than twice that of noninfected patients (25% [1688/6659] vs 11% [ 682/6352], respectively P < .001), as was the hospital mortality rate (33% [2201/6659] vs 15% [ 942/6352], respectively P < .001) (adjusted odds ratio for risk of hospital mortality, 1.51 95% confidence interval, 1.36-1.68 P < .001). Infections are common in patients in contemporary ICUs, and risk of infection increases with duration of ICU stay. In this large cohort, infection was independently associated with an increased risk of hospital death.
Publisher: Springer Science and Business Media LLC
Date: 12-2017
Publisher: Springer Science and Business Media LLC
Date: 18-09-2019
DOI: 10.1186/S13054-019-2597-0
Abstract: Metabolic alterations in the critically ill have been studied for more than a century, but the heterogeneity of the critically ill patient population, the varying duration and severity of the acute phase of illness, and the many confounding factors have hindered progress in the field. These factors may explain why management of metabolic alterations and related conditions in critically ill patients has for many years been guided by recommendations based essentially on expert opinion. Over the last decade, a number of randomized controlled trials have been conducted, providing us with important population-level evidence that refutes several longstanding paradigms. However, between-patient variation means there is still substantial uncertainty when translating population-level evidence to in iduals. A cornerstone of metabolic care is nutrition, for which there is a multifold of published guidelines that agree on many issues but disagree on others. Using a series of nine questions, we provide a review of the latest data in this field and a background to promote efforts to address the need for international consistency in recommendations related to the metabolic care of the critically ill patient. Our purpose is not to replace existing guidelines, but to comment on differences and add perspective.
Publisher: Cold Spring Harbor Laboratory
Date: 14-11-2022
DOI: 10.1101/2022.11.14.22282287
Abstract: Neonatal mortality might be higher in urban areas. This paper aims to minimize challenges related to misclassification of neonatal deaths and stillbirths, and oversimplification of the variation in urban environments to accurately estimate the direction and strength of the association between urban residence and neonatal erinatal mortality in Tanzania. The Tanzania Demographic and Health Survey (DHS) 2015-16 was used to assess birth outcomes for 8,915 pregnancies among 6,156 women of reproductive age, by urban or rural categorization in the DHS and based on satellite imagery. The coordinates of 527 DHS clusters were spatially overlaid with the 2015 Global Human Settlement Layer, showing the degree of urbanisation based on built environment and population density. A three-category urbanicity measure (core urban, semi-urban, and rural) was defined and compared to the binary DHS measure. Travel time to the nearest hospital was modelled using least-cost path algorithm for each cluster. Bivariate and multi-level multivariable logistic regression models were constructed to explore associations between urbanicity and neonatal erinatal deaths. Both perinatal and neonatal mortality rates were highest in core urban and lowest in rural clusters. Bivariate models showed higher odds of neonatal death (OR=1.85 95% CI: 1.12, 3.08) and perinatal death (OR=1.60 95% CI 1.12, 2.30) in core urban compared to rural clusters. In multivariable models, these associations had the same direction and size, but were no longer statistically significant. Travel time to nearest hospital was not associated with neonatal or perinatal mortality. Addressing the higher rates of neonatal and perinatal mortality in densely populated urban areas is critical for Tanzania to meet national and global reduction targets. Urban populations are erse, and certain neighbourhoods or sub-groups may be disproportionately affected by poor birth outcomes. Research must s le within and across urban areas to differentiate, understand and minimize risks specific to urban settings. - Urban advantage in health outcomes has been questioned, both for adult and child mortality - An analysis of neonatal mortality using Demographic and Health Survey data in Tanzania in 2015-16 showed double risk in urban compared to rural areas - This phenomenon might be occurring in other sub-Saharan African countries - Categorisation of locations as urban or rural on the 2015-16 Demographic and Health Survey in Tanzania is both simplistic and inaccurate - Risks of neonatal and perinatal mortality are highest in core, densely populated urban areas in mainland Tanzania, and lowest in rural areas - Travel time to nearest public hospital was not associated with neonatal or perinatal mortality in mainland Tanzania - Extent of urbanicity as an exposure follows a spectrum and needs to be measured and understood as such - Explanatory models specific to neonatal and perinatal mortality in core urban areas are urgently needed to guide actions toward reducing existing high rate - Known risk factors such as anaemia and young maternal age continue to play a role in neonatal and perinatal mortality and must be urgently addressed.
Publisher: Elsevier BV
Date: 10-2011
DOI: 10.1016/J.IJANTIMICAG.2011.05.013
Abstract: Controversy continues regarding whether the presence of meticillin resistance increases mortality risk in Staphylococcus aureus infections. In this study, we assessed the role of meticillin resistance in survival of patients with S. aureus infection included in the EPIC II point-prevalence study of infection in critically ill patients performed on 8 May 2007. Demographic, physiological, bacteriological and therapeutic data were collected for 13796 adult patients in 1265 participating Intensive Care Units (ICUs) from 75 countries on the study day. ICU and hospital outcomes were recorded. Characteristics of patients with meticillin-sensitive S. aureus (MSSA) and meticillin-resistant S. aureus (MRSA) infections were compared. Co-morbidities, age, Simplified Acute Physiology Score (SAPS) II, site of infection, geographical region and MRSA/MSSA were entered into a multivariate model, and adjusted odds ratios (ORs) [95% confidence interval (CI)] for ICU and hospital mortality rates were calculated. On the study day, 7087 (51%) of the 13796 patients were classified as infected. There were 494 patients with MRSA infections and 505 patients with MSSA infections. There were no significant differences between the two groups in use of mechanical ventilation or haemofiltration/haemodialysis. Cancer and chronic renal failure were more prevalent in MRSA than in MSSA patients. ICU mortality rates were 29.1% and 20.5%, respectively (P<0.01) and corresponding hospital mortality rates were 36.4% and 27.0% (P<0.01). Multivariate analysis of hospital mortality for MRSA infection showed an adjusted OR of 1.46 (95% CI 1.03-2.06) (P=0.03). In ICU patients, MRSA infection is therefore independently associated with an almost 50% higher likelihood of hospital death compared with MSSA infection.
Publisher: Springer Science and Business Media LLC
Date: 27-01-2017
DOI: 10.1007/S00134-017-4677-4
Abstract: Because of its high incidence and clinical complexity, sepsis is a major challenge to clinicians and researchers and a global burden to healthcare systems and society. Despite recent progress, short- and long-term morbidity, mortality and costs remain high in both developed and developing countries. Thus, further improvements in supportive interventions and organisation of care are likely to have a substantial impact upon global health. In this narrative review, invited experts describe the challenges and progress to be made in sepsis research and care in the near future. We focus on supportive care (pulmonary, endocrine, renal, and nutritional support, mediator modulation and precision medicine), organisational themes (guidelines, outcome measures and stakeholder involvement) and clinical research as key areas to improving the care and outcomes of patients with sepsis.
Publisher: Springer Science and Business Media LLC
Date: 09-05-2018
Publisher: American Society for Microbiology
Date: 06-2011
DOI: 10.1128/AAC.01708-10
Abstract: Despite the development of novel antibiotics active against Gram-positive bacteria, vancomycin generally remains the first treatment, although rapidly achieving concentrations associated with maximal efficacy provides an unresolved challenge. The objective of this study was to conduct a population pharmacokinetic analysis of vancomycin in a large population of critically ill patients. This was a retrospective data collection of 206 adult septic critically ill patients who were administered vancomycin as a loading dose followed by continuous infusion. The concentration-versus-time data for vancomycin in serum was analyzed by a nonlinear mixed-effects modeling approach using NONMEM. Monte Carlo simulations were performed using the final covariate model. We found that the best population pharmacokinetic model consisted of a one-compartment linear model with combined proportional and additive residual unknown variability. The volume of distribution of vancomycin (1.5 liters/kg) was described by total body weight and clearance (4.6 liters/h) by 24-hour urinary creatinine clearance (CrCl), normalized to body surface area. Simulation data showed that a 35-mg/kg loading dose was necessary to rapidly achieve vancomycin concentrations of 20 mg/liter. Daily vancomycin requirements were dependent on CrCl, such that a patient with a CrCl of 100 ml/min/1.73 m 2 would require at least 35 mg/kg per day by continuous infusion to maintain target concentrations. In conclusion, we have found that higher-than-recommended loading and daily doses of vancomycin seem to be necessary to rapidly achieve therapeutic serum concentrations in these patients.
Publisher: Mary Ann Liebert Inc
Date: 08-2014
DOI: 10.1089/SUR.2012.228
Abstract: Infectious complications are frequent in severe acute pancreatitis (SAP) but multinational epidemiologic data are lacking. The aim of the study was to analyze the characteristics of the infectious complications and antimicrobial use in this setting. One-day point prevalence study of infection in critically ill patients (Extended Prevalence of Infection in the ICU-II study), performed in 1,265 ICUs in 75 countries. Of the 13,796 patients in the study, 159 were admitted with SAP. One-hundred sixteen (73%) had infections: 31% intra-abdominal, 16% extra-abdominal, and 26% both. Gram-negative bacteria were more prevalent than gram-positive organisms, anaerobes, or fungi. Therapeutically, penicillins and other beta-lactams were used most frequently. Prophylactic antibiotics were administered to 24% of the patients with SAP. Infections are frequent in patients admitted with SAP most are intra-abdominal infections. Microbiology is erse with gram-negative micro-organisms most frequently isolated. Most patients admitted to the ICU for SAP receive antibiotics at some point.
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.JCRC.2016.06.014
Abstract: Demand for intensive care unit (ICU) resources often exceeds supply, and shortages of ICU beds and staff are likely to persist. Triage requires careful weighing of the benefits and risks involved in ICU admission while striving to guarantee fair distribution of available resources. We must ensure that the patients who occupy ICU beds are those most likely to benefit from the ICU's specialized technology and professionals. Although prognosticating is not an exact science, preference should be given to patients who are more likely to survive if admitted to the ICU but unlikely to survive or likely to have more significant morbidity if not admitted. To provide general guidance for intensivists in ICU triage decisions, a task force of the World Federation of Societies of Intensive and Critical Care Medicine addressed 4 basic questions regarding this process. The team made recommendations and concluded that triage should be led by intensivists considering input from nurses, emergency medicine professionals, hospitalists, surgeons, and allied professionals. Triage algorithms and protocols can be useful but can never supplant the role of skilled intensivists basing their decisions on input from multidisciplinary teams. Infrastructures need to be organized efficiently both within in idual hospitals and at the regional level. When resources are critically limited, patients may be refused ICU admission if others may benefit more on the basis of the principle of distributive justice.
Publisher: Elsevier BV
Date: 05-2015
Publisher: Springer Science and Business Media LLC
Date: 2013
DOI: 10.1186/CC12547
Publisher: Massachusetts Medical Society
Date: 12-03-2015
DOI: 10.1056/NEJMC1500327
Publisher: Springer Science and Business Media LLC
Date: 18-01-2017
DOI: 10.1007/S00134-017-4683-6
Abstract: To provide an update to "Surviving Sepsis C aign Guidelines for Management of Sepsis and Septic Shock: 2012". A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.
Publisher: Springer Science and Business Media LLC
Date: 04-12-2017
DOI: 10.1007/S00134-017-5004-9
Abstract: Polymyxin B-immobilized hemoperfusion (PMX-HP) is an adjuvant therapy for sepsis or septic shock that clears circulating endotoxin. Prior trials have shown that PMX-HP improves surrogate endpoints. We aimed to conduct an evidence synthesis to evaluate the efficacy and safety of PMX-HP in critically ill adult patients with sepsis or septic shock. We searched for randomized controlled trials (RCTs) in MEDLINE, EMBASE, the Cochrane Library, the Health Technology Assessment Database, CINAHL, "Igaku Chuo Zasshi", the National Institute of Health Clinical Trials Register, the World Health Organization International Clinical Trials Registry Platform, the University Hospital Medical Information Network Clinical Trials Registry, the reference lists of retrieved articles, and publications by manufacturers of PMX-HP. The primary outcomes were 28-day all-cause mortality, the number of patients with at least one serious adverse event, and organ dysfunction scores. The GRADE methodology for the certainty of evidence was used. Six trials (857 participants weighted mean age 62.5 years) proved eligible. Patient-oriented primary outcomes were assessed. The pooled risk ratio (RR) for 28-day mortality associated with PMX-HP was 1.03 [95% confidence interval (CI) 0.78-1.36 I There is currently insufficient evidence to support the routine use of PMX-HP to treat patients with sepsis or septic shock. PROSPERO International Prospective Register of Systematic Reviews (CRD42016038356).
Publisher: American Society for Microbiology
Date: 08-2016
DOI: 10.1128/AAC.00330-16
Abstract: Despite the development of new agents with activity against Gram-positive bacteria, vancomycin remains one of the primary antibiotics for critically ill septic patients. Because sepsis can alter antimicrobial pharmacokinetics, the development of an appropriate dosing strategy to provide adequate concentrations is crucial. The aim of this study was to prospectively validate a new dosing regimen of vancomycin given by continuous infusion (CI) to septic patients. We included all adult septic patients admitted to a mixed intensive care unit (ICU) between January 2012 and May 2013, who were treated with a new vancomycin CI regimen consisting of a loading dose of 35 mg/kg of body weight given as a 4-h infusion, followed by a daily CI dose adapted to creatinine clearance (CrCL), as estimated by the Cockcroft-Gault formula (median dose, 2,112 [1,500 to 2,838] mg). Vancomycin concentrations were measured at the end of the loading dose (T1), at 12 h (T2), at 24 h (T3), and the day after the start of therapy (T4). Vancomycin concentrations of 20 to 30 mg/liter at T2, T3, and T4 were considered adequate. A total of 107 patients (72% male) were included. Median age, weight, and CrCL were 59 (interquartile range [IQR], 48 to 71) years, 75 (IQR, 65 to 85) kg, and 94 (IQR, 56 to 140) ml/min, respectively. Vancomycin concentrations were 44 (IQR, 37 to 49), 25 (IQR, 21 to 32), 22 (IQR, 19 to 28), and 26 (IQR, 22 to 29) mg/liter at T1, T2, T3, and T4, respectively. Concentrations were adequate in 56% (60/107) of patients at T2, in 54% (57/105) at T3, and in 73% (41/56) at T4. This vancomycin regimen permitted rapid attainment of target concentrations in serum for most patients. Concentrations were insufficient in only 16% of patients at 12 h of treatment.
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1093/BJA/AEU300
Publisher: Springer Science and Business Media LLC
Date: 08-11-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2019
DOI: 10.1213/ANE.0000000000003972
Abstract: Wired electrocardiogram monitors are an important component of current perioperative monitoring. Wireless monitoring units could help reduce the number of cables attached to patients and thus improve anesthesia ergonomics and patient management. However, there is concern that electromagnetic interference generated by electrosurgical units may prevent effective wireless signals in the operating room. To evaluate the extent of this problem, we developed a Bluetooth electrocardiogram prototype monitor and compared its electrocardiogram traces to those captured with a standard wired electrocardiogram monitor in our operating room. Bluetooth electrocardiogram and standard electrocardiogram traces captured from 10 patients undergoing surgical procedures that required use of an electrosurgical unit were compared by analysis of the durations of the P wave, QRS complex, and T wave and the position of the ST segment from the isoelectric line. The impact of the electrosurgical units on the Bluetooth electrocardiogram and S-electrocardiogram recordings was also assessed. There were no clinically relevant differences in P wave, QRS complex, or T-wave durations (0.006, 0.004, and 0.017 seconds, respectively) between Bluetooth electrocardiogram and standard electrocardiogram or in the position of the ST segment from the isoelectric line (0.02 mV). Mean differences were near zero, and Bland–Altman limits of agreement for in idual differences were narrow (−0.035 to 0.047, −0.03 to 0.038, and −0.112 to 0.078 seconds for P wave, QRS complex, and T-wave durations, respectively, and −0.13 to 0.17 mV for ST segment position). Electrosurgical units use electrically disrupted Bluetooth electrocardiogram and standard electrocardiogram signals, but there was no electromagnetic interference effect on the Bluetooth electrocardiogram signals. Wireless electrocardiogram using Bluetooth can be reliably used in the operating room. The electrosurgical unit induces electric rather than electromagnetic artifacts, thus affecting wired and wireless electrocardiogram in a similar fashion.
Publisher: Springer Science and Business Media LLC
Date: 13-03-2017
DOI: 10.1007/S00134-017-4757-5
Abstract: We present areas of uncertainty concerning intensive care unit-acquired weakness (ICUAW) and identify areas for future research. Age, pre-ICU functional and cognitive state, concurrent illness, frailty, and health trajectories impact outcomes and should be assessed to stratify patients. In the ICU, early assessment of limb and diaphragm muscle strength and function using nonvolitional tests may be useful, but comparison with established methods of global and specific muscle strength and physical function and determination of their reliability and normal values would be important to advance these techniques. Serial measurements of limb and respiratory muscle strength, and systematic screening for dysphagia, would be helpful to clarify if and how weakness of these muscle groups is independently associated with outcome. ICUAW, delirium, and sedatives and analgesics may interact with each other, lifying the effects of each in idual factor. Reduced mobility in patients with hypoactive delirium needs investigations into dysfunction of central and peripheral nervous system motor pathways. Interventional nutritional studies should include muscle mass, strength, and physical function as outcomes, and prioritize elucidation of mechanisms. At follow-up, ICU survivors may suffer from prolonged muscle weakness and wasting and other physical impairments, as well as fatigue without demonstrable weakness on examination. Further studies should evaluate the prevalence and severity of fatigue in ICU survivors and define its association with psychiatric disorders, pain, cognitive impairment, and axonal loss. Finally, methodological issues, including accounting for baseline status, handling of missing data, and inclusion of patient-centered outcome measures should be addressed in future studies.
Publisher: Springer Science and Business Media LLC
Date: 12-2015
Publisher: BMJ
Date: 04-2023
DOI: 10.1136/BMJGH-2022-011253
Abstract: Recent studies suggest that the urban advantage of lower neonatal mortality in urban compared with rural areas may be reversing, but methodological challenges include misclassification of neonatal deaths and stillbirths, and oversimplification of the variation in urban environments. We address these challenges and assess the association between urban residence and neonatal erinatal mortality in Tanzania. The Tanzania Demographic and Health Survey (DHS) 2015–2016 was used to assess birth outcomes for 8915 pregnancies among 6156 women of reproductive age, by urban or rural categorisation in the DHS and based on satellite imagery. The coordinates of 527 DHS clusters were spatially overlaid with the 2015 Global Human Settlement Layer, showing the degree of urbanisation based on built environment and population density. A three-category urbanicity measure (core urban, semi-urban and rural) was defined and compared with the binary DHS measure. Travel time to the nearest hospital was modelled using least-cost path algorithm for each cluster. Bivariate and multilevel multivariable logistic regression models were constructed to explore associations between urbanicity and neonatal erinatal deaths. Both neonatal and perinatal mortality rates were highest in core urban and lowest in rural clusters. Bivariate models showed higher odds of neonatal death (OR=1.85 95% CI 1.12 to 3.08) and perinatal death (OR=1.60 95% CI 1.12 to 2.30) in core urban compared with rural clusters. In multivariable models, these associations had the same direction and size, but were no longer statistically significant. Travel time to the nearest hospital was not associated with neonatal or perinatal mortality. Addressing high rates of neonatal and perinatal mortality in densely populated urban areas is critical for Tanzania to meet national and global reduction targets. Urban populations are erse, and certain neighbourhoods or subgroups may be disproportionately affected by poor birth outcomes. Research must capture, understand and minimise risks specific to urban settings.
Publisher: Springer Science and Business Media LLC
Date: 03-1993
DOI: 10.1007/BF01720538
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2015
DOI: 10.1097/ALN.0000000000000511
Abstract: Several studies have indicated that a restrictive erythrocyte transfusion strategy is as safe as a liberal one in critically ill patients, but there is no clear evidence to support the superiority of any perioperative transfusion strategy in patients with cancer. In a randomized, controlled, parallel-group, double-blind (patients and outcome assessors) superiority trial in the intensive care unit of a tertiary oncology hospital, the authors evaluated whether a restrictive strategy of erythrocyte transfusion (transfusion when hemoglobin concentration & g/dl) was superior to a liberal one (transfusion when hemoglobin concentration & g/dl) for reducing mortality and severe clinical complications among patients having major cancer surgery. All adult patients with cancer having major abdominal surgery who required postoperative intensive care were included and randomly allocated to treatment with the liberal or the restrictive erythrocyte transfusion strategy. The primary outcome was a composite endpoint of mortality and morbidity. A total of 198 patients were included as follows: 101 in the restrictive group and 97 in the liberal group. The primary composite endpoint occurred in 19.6% (95% CI, 12.9 to 28.6%) of patients in the liberal-strategy group and in 35.6% (27.0 to 45.4%) of patients in the restrictive-strategy group (P = 0.012). Compared with the restrictive strategy, the liberal transfusion strategy was associated with an absolute risk reduction for the composite outcome of 16% (3.8 to 28.2%) and a number needed to treat of 6.2 (3.5 to 26.5). A liberal erythrocyte transfusion strategy with a hemoglobin trigger of 9 g/dl was associated with fewer major postoperative complications in patients having major cancer surgery compared with a restrictive strategy.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2002
DOI: 10.1097/00003246-200207000-00039
Abstract: To describe the development, organization, and operation of several collaborative groups conducting investigator-initiated multicenter clinical research in adult critical care. To review the process by which investigator-initiated critical care clinical research groups were created using ex les from Europe, Australia, the United States, and Canada. Various models of group structure and function are discussed, highlighting complementary approaches to protocol development, multicenter study management, and project funding. Published peer review research and unpublished terms of reference documents on the structure and function of these groups. The overall goal of clinical critical care research groups engaged in multicenter studies is to improve patient outcomes through conducting large, rigorous investigations. Research programs we reviewed included the following: a) multicenter epidemiologic studies and surveys b) technology evaluations of mechanical ventilation c) investigations focused on three priority fields (acute lung injury, infection, and acute brain injury) d) a series of randomized trials of treatments for one syndrome (acute respiratory distress syndrome) and e) erse methodologies addressing several clinical problems. The structure and function of these research groups differ according to their historical development, research culture, and enabling resources. Specific protocols emerge from clinical questions generated by investigators or from collectively prioritized research agendas. Project funding includes government support, peer-review grants, intensive care foundations, industry, local hospital funds, and hybrid models. Infrastructure for study management varies widely. Several national and international groups have engaged in investigator-initiated multicenter critical care research. The development, organization, and operational methods of these groups illustrate several collaborative models for clinical investigations in the intensive care unit. Common characteristics of these groups are a cohesive spirit, a sense of mission to achieve shared research goals, and acknowledgment that such an organization is much more than the sum of its parts.
Publisher: Elsevier BV
Date: 2010
Publisher: Massachusetts Medical Society
Date: 08-03-2001
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2017
DOI: 10.1097/CCM.0000000000002255
Abstract: To provide an update to “Surviving Sepsis C aign Guidelines for Management of Sepsis and Septic Shock: 2012.” A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.
Publisher: Springer Science and Business Media LLC
Date: 26-03-2013
Abstract: Allogeneic red blood cell (RBC) transfusion has been proposed as a negative indicator of quality in cardiac surgery. Hospital length of stay (LOS) may be a surrogate of poor outcome in transfused patients. Data from 502 patients included in Transfusion Requirements After Cardiac Surgery (TRACS) study were analyzed to assess the relationship between RBC transfusion and hospital LOS in patients undergoing cardiac surgery and enrolled in the TRACS study. According to the status of RBC transfusion, patients were categorized into the following three groups: 1) 199 patients (40%) who did not receive RBC, 2) 241 patients (48%) who received 3 RBC units or fewer (low transfusion requirement group), and 3) 62 patients (12%) who received more than 3 RBC units (high transfusion requirement group). In a multivariable Cox proportional hazards model, the following factors were predictive of a prolonged hospital length of stay: age higher than 65 years, EuroSCORE, valvular surgery, combined procedure, LVEF lower than 40% and RBC transfusion of 3 units. RBC transfusion is an independent risk factor for increased LOS in patients undergoing cardiac surgery. This finding highlights the adequacy of a restrictive transfusion therapy in patients undergoing cardiac surgery. Clinicaltrials.gov identifier: NCT01021631 .
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2015
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.JTCVS.2013.02.003
Abstract: Although hyperlactatemia after cardiac surgery is common, the implications of raised levels remain controversial. The aim of this study was to evaluate whether high lactate levels after cardiac surgery are predictors of major complications including mortality. This was a substudy of TRACS (Transfusion Requirements After Cardiac Surgery), which was designed as a prospective, randomized, controlled trial evaluating the effects of a transfusion strategy on morbidity and mortality. Of the 502 patients enrolled, 52 (10%) had at least 1 major complication. Patients with complications were older, had a higher EuroSCORE, lower left ventricular ejection fraction, lower preoperative hemoglobin, a higher prevalence of renal disease, and received more blood transfusions than the group without complications. Lactate levels were higher in the group with complications at the end of surgery (3.6 mmol/L [2.8-5.1] vs 3.3 mmol/L [2.2-4.8] P = .018), immediately after intensive care unit (ICU) admission (0 hour) (4.4 mmol/L [3.1-8.4] vs 4 mmol/L [2.6-6.4] P = .048) 6 hours (4 mmol/L [2.7-5.8] vs 2.6 mmol/L [2-3.6], P < .001), and 12 hours after admission (2.3 mmol/L [1.8-3.2] vs 1.7 mmol/L [1.3-2] P < .001). In a multivariate model, higher age (odds ratio [OR], 1.048, 95% confidence interval [CI], 1.011-1.086 P = .010), left ventricular ejection fraction (LVEF) lower than 40% (OR, 3.03 95% CI, 1.200-7.510 P = .019 compared with LVEF of 40%-59% OR, 3.571 95% CI, 1.503-8.196 P = .004 compared with LVEF higher than 60%), higher EuroSCORE (OR, 1.138 95% CI 1.007-1.285 P = .038), red blood cell transfusion (OR, 1.230 95% CI, 1.086-1.393 P = .001), and lactate levels 6 hours after ICU admission (OR, 3.28, 95% CI 1.61-6.69 P = .001) are predictors of major complications. Hyperlactatemia 6 hours after ICU admission is an independent risk factor for worse outcomes in adult patients after cardiac surgery.
Publisher: Elsevier BV
Date: 06-2013
DOI: 10.1016/J.IJANTIMICAG.2013.01.018
Abstract: Treatment of resistant bacteria such as meticillin-resistant Staphylococcus aureus (MRSA) relies on achieving adequate antibiotic concentrations at the site of infection. Strategies to attain such targets in septic critically ill patients receiving renal replacement therapy (RRT) are uncommon but could be useful for increasing the likelihood of therapeutic dosing. The aim of this study was to conduct a population pharmacokinetic (PK) analysis in septic patients undergoing continuous RRT and to determine which parameters were associated with inadequate vancomycin concentrations. In total, 81 patients with 199 blood s les were included in the study. All patients received vancomycin dosing according to the local protocol, which included a weight-based loading dose followed by continuous infusion. The vancomycin concentration-time points were adequately described with a one-compartment model with zero order input. The median population PK estimate for vancomycin clearance (CL) was 2.9 L/h [interquartile range (IQR) 2.4-3.4 L/h] and for volume of distribution (Vd) was 0.8 L/kg (IQR 0.6-1.1 L/kg). The goodness-of-fit plots for the model were adequate. When covariates were tested, none were found to adequately explain changing vancomycin CL or Vd in the population PK model. In particular, the lack of correlation between CL and RRT settings was likely due to the multiple confounders known to influence antibiotic prescription in this setting. These data provide a cautionary tale of the challenges of describing pharmacokinetics in critically ill patients receiving RRT and highlights the need for a detailed, prospective, multicentre study to better inform dosing practice.
Publisher: Massachusetts Medical Society
Date: 15-08-2013
DOI: 10.1056/NEJME1304035
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: Kenya
No related grants have been discovered for Jean-Louis Vincent.