ORCID Profile
0000-0002-0576-8874
Current Organisation
University of Oxford
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Publisher: Oxford University Press (OUP)
Date: 23-08-2023
DOI: 10.1093/EURHEARTJ/EHAD535
Abstract: Effervescent formulations of paracetamol containing sodium bicarbonate have been reported to associate with increased blood pressure and a higher risk of cardiovascular diseases and all-cause mortality. Given the major implications of these findings, the reported associations were re-examined. Using linked electronic health records data, a cohort of 475 442 UK in iduals with at least one prescription of paracetamol, aged between 60 and 90 years, was identified. Outcomes in patients taking sodium-based paracetamol were compared with those taking non–sodium-based formulations of the same. Using a deep learning approach, associations with systolic blood pressure (SBP), major cardiovascular events (myocardial infarction, heart failure, and stroke), and all-cause mortality within 1 year after baseline were investigated. A total of 460 980 and 14 462 patients were identified for the non–sodium-based and sodium-based paracetamol exposure groups, respectively (mean age: 74 years 64% women). Analysis revealed no difference in SBP [mean difference −0.04 mmHg (95% confidence interval −0.51, 0.43)] and no association with major cardiovascular events [relative risk (RR) 1.03 (0.91, 1.16)]. Sodium-based paracetamol showed a positive association with all-cause mortality [RR 1.46 (1.40, 1.52)]. However, after further accounting of other sources of residual confounding, the observed association attenuated towards the null [RR 1.08 (1.01, 1.16)]. Exploratory analyses revealed dysphagia and related conditions as major sources of uncontrolled confounding by indication for this association. This study does not support previous suggestions of increased SBP and an elevated risk of cardiovascular events from short-term use of sodium bicarbonate paracetamol in routine clinical practice.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2023
DOI: 10.1161/HYPERTENSIONAHA.123.21496
Abstract: Whether the relative effects of blood pressure (BP)–lowering treatment on cardiovascular outcomes differ by sex, particularly when BP is not substantially elevated, has been uncertain. We conducted an in idual participant-level data meta-analysis of randomized controlled trials of pharmacological BP lowering. We pooled the data and categorized participants by sex, systolic BP categories in 10-mm Hg increments from to ≥170 mm Hg, and age categories spanning from to ≥85 years. We used fixed-effect 1-stage in idual participant-level data meta-analyses and applied Cox proportional hazard models, stratified by trial, to analyze the data. We included data from 51 randomized controlled trials involving 358 635 (42% women) participants. Over 4.2 years of median follow-up, a 5-mm Hg reduction in systolic BP decreased the risk of major cardiovascular events both in women and men (hazard ratio [95% CI], 0.92 [0.89–0.95] for women and 0.90 [0.88–0.93] for men P for interaction, 1). There was no evidence for heterogeneity of relative treatment effects by sex for the major cardiovascular disease, its components, or across the different baseline BP categories (all P for interaction, ≥0.57). The effects in women and men were consistent across age categories and the types of antihypertensive medications (all P for interaction, ≥0.14). The effects of BP reduction were similar in women and men across all BP and age categories at randomization and with no evidence to suggest that drug classes had differing effects by sex. This study does not substantiate sex-based differences in BP-lowering treatment.
Publisher: Public Library of Science (PLoS)
Date: 17-06-2021
DOI: 10.1371/JOURNAL.PMED.1003674
Abstract: Our knowledge of how to better manage elevated blood pressure (BP) in the presence of comorbidities is limited, in part due to exclusion or underrepresentation of patients with multiple chronic conditions from major clinical trials. We aimed to investigate the burden and types of comorbidities in patients with hypertension and to assess how such comorbidities and other variables affect BP levels over time. In this multiple landmark cohort study, we used linked electronic health records from the United Kingdom Clinical Practice Research Datalink (CPRD) to compare systolic blood pressure (SBP) levels in 295,487 patients (51% women) aged 61.5 (SD = 13.1) years with first recorded diagnosis of hypertension between 2000 and 2014, by type and numbers of major comorbidities, from at least 5 years before and up to 10 years after hypertension diagnosis. Time-updated multivariable linear regression analyses showed that the presence of more comorbidities was associated with lower SBP during follow-up. In hypertensive patients without comorbidities, mean SBP at diagnosis and at 10 years were 162.3 mm Hg (95% confidence interval [CI] 162.0 to 162.6) and 140.5 mm Hg (95% CI 140.4 to 140.6), respectively in hypertensive patients with ≥5 comorbidities, these were 157.3 mm Hg (95% CI 156.9 to 157.6) and 136.8 mm Hg (95% 136.4 to 137.3), respectively. This inverse association between numbers of comorbidities and SBP was not specific to particular types of comorbidities, although associations were stronger in those with preexisting cardiovascular disease. Retrospective analysis of recorded SBP showed that the difference in mean SBP 5 years before diagnosis between those without and with ≥5 comorbidities was −9 mm Hg (95% CI −9.7 to −8.3), suggesting that mean recorded SBP already differed according to the presence of comorbidity before baseline. Within 1 year after the diagnosis, SBP substantially declined, but subsequent SBP changes across comorbidity status were modest, with no evidence of a more rapid decline in those with more or specific types of comorbidities. We identified factors, such as prescriptions of antihypertensive drugs and frequency of healthcare visits, that can explain SBP differences according to numbers or types of comorbidities, but these factors only partly explained the recorded SBP differences. Nevertheless, some limitations have to be considered including the possibility that diagnosis of some conditions may not have been recorded, varying degrees of missing data inherent in analytical datasets extracted from routine health records, and greater measurement errors in clinical measurements taken in routine practices than those taken in well-controlled clinical study settings. BP levels at which patients were diagnosed with hypertension varied substantially according to the presence of comorbidities and were lowest in patients with multi-morbidity. Our findings suggest that this early selection bias of hypertension diagnosis at different BP levels was a key determinant of long-term differences in BP by comorbidity status. The lack of a more rapid decline in SBP in those with multi-morbidity provides some reassurance for BP treatment in these high-risk in iduals.
Publisher: BMJ
Date: 20-01-2022
DOI: 10.1136/HEARTJNL-2021-320171
Abstract: Evidence from randomised trials of pharmacological treatments on long-term blood pressure (BP) reduction is limited. We investigated the antihypertensive drug effects on BP over time and across different participant characteristics. We conducted an in idual patient-level data meta-analysis of 52 large-scale randomised clinical trials in the Blood Pressure Lowering Treatment Trialists’ Collaboration using mixed models to examine treatment effects on BP over 4 years of mean follow-up. There were 363 684 participants (42% women), with baseline mean age=65 years and mean systolic/diastolic BP=152/87 mm Hg, and among whom 19% were current smokers, 49% had cardiovascular disease, 28% had diabetes and 69% were taking antihypertensive treatment at baseline. Drugs were effective in lowering BP showing maximal effect after 12 months and gradually attenuating towards later years. Based on measures taken ≥12 months postrandomisation, mean systolic/diastolic BP difference (95% CI) between more and less intense BP-lowering treatment was −11.1 (−11.3 to −10.8)/−5.6 (−5.7 to −5.4) mm Hg between active treatment and placebo was −5.1 (−5.3 to −5.0)/−2.3 (−2.4 to −2.2) mm Hg and between active and control arms for drug comparison trials was −1.4 (−1.5 to −1.3)/−0.6 (−0.7 to −0.6) mm Hg. BP reductions were observed across different baseline BP values and ages, and by sex, history of cardiovascular disease and diabetes and prior antihypertensive treatment use. These findings suggest that BP-lowering pharmacotherapy is effective in lowering BP, up to 4 years on average, in people with different characteristics. Appropriate treatment strategies are needed to sustain substantive long-term BP reductions.
Publisher: Cold Spring Harbor Laboratory
Date: 23-02-2021
DOI: 10.1101/2021.02.19.21252066
Abstract: Evidence from randomised trials on long-term blood pressure (BP) reduction from pharmacologic treatment is limited. To investigate the effects of antihypertensive drugs on long-term BP change and examine its variation over time and among people with different clinical characteristics In idual participant-level data meta-analysis The Blood Pressure Lowering Treatment Trialists’ Collaboration involving 51 large-scale long-term randomised clinical trials 352,744 people (42% women) with mean age of 65 years and mean baseline systolic/diastolic BP of 152/87 mmHg, of whom 18% were current smokers, 50% had cardiovascular disease, 29% had diabetes, and 72% were taking antihypertensive treatment at baseline Pharmacological BP-lowering treatment Difference in longitudinal changes in systolic and diastolic BP between randomised treatment arms over an average follow-up of four years Drugs were effective in lowering BP, with the maximum effect becoming apparent after 12-month follow-up and with gradual attenuation towards later years. Based on measures taken ≥12 months post-randomisation, more intense BP-lowering treatment reduced systolic/diastolic BP (95% confidence interval) by −11.2 (−11.4 to −11.0)/−5.6 (−5.8 to −5.5) mmHg than less intense treatment active treatment by −5.1 (−5.3 to −5.0)/−2.3 (−2.4 to −2.2) mmHg lower than placebo, and active arm by −1.4 (−1.5 to −1.3)/−0.6 (−0.7 to −0.6) mmHg lower than the control arm for drug class comparison trials. BP reductions were consistently observed across a wide range of baseline BP values and ages, and by sex, history of cardiovascular disease and diabetes, and prior antihypertensive treatment use. Pharmacological agents were effective in lowering long-term BP among in iduals with a wide range of characteristics, but the net between-group reductions were modest, which is partly attributable to the intended trial goals.
Publisher: Public Library of Science (PLoS)
Date: 06-2021
DOI: 10.1371/JOURNAL.PMED.1003599
Abstract: Randomised evidence on the efficacy of blood pressure (BP)-lowering treatment to reduce cardiovascular risk in patients with atrial fibrillation (AF) is limited. Therefore, this study aimed to compare the effects of BP-lowering drugs in patients with and without AF at baseline. The study was based on the resource provided by the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC), in which in idual participant data (IPD) were extracted from trials with over 1,000 patient-years of follow-up in each arm, and that had randomly assigned patients to different classes of BP-lowering drugs, BP-lowering drugs versus placebo, or more versus less intensive BP-lowering regimens. For this study, only trials that had collected information on AF status at baseline were included. The effects of BP-lowering treatment on a composite endpoint of major cardiovascular events (stroke, ischaemic heart disease or heart failure) according to AF status at baseline were estimated using fixed-effect one-stage IPD meta-analyses based on Cox proportional hazards models stratified by trial. Furthermore, to assess whether the associations between the intensity of BP reduction and cardiovascular outcomes are similar in those with and without AF at baseline, we used a meta-regression. From the full BPLTTC database, 28 trials (145,653 participants) were excluded because AF status at baseline was uncertain or unavailable. A total of 22 trials were included with 188,570 patients, of whom 13,266 (7%) had AF at baseline. Risk of bias assessment showed that 20 trials were at low risk of bias and 2 trials at moderate risk. Meta-regression showed that relative risk reductions were proportional to trial-level intensity of BP lowering in patients with and without AF at baseline. Over 4.5 years of median follow-up, a 5-mm Hg systolic BP (SBP) reduction lowered the risk of major cardiovascular events both in patients with AF (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.83 to 1.00) and in patients without AF at baseline (HR 0.91, 95% CI 0.88 to 0.93), with no difference between subgroups. There was no evidence for heterogeneity of treatment effects by baseline SBP or drug class in patients with AF at baseline. The findings of this study need to be interpreted in light of its potential limitations, such as the limited number of trials, limitation in ascertaining AF cases due to the nature of the arrhythmia and measuring BP in patients with AF. In this meta-analysis, we found that BP-lowering treatment reduces the risk of major cardiovascular events similarly in in iduals with and without AF. Pharmacological BP lowering for prevention of cardiovascular events should be recommended in patients with AF.
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.ADDBEH.2013.09.013
Abstract: Tramadol hydrochloride is a common prescription pain reliever that is structurally similar to morphine and codeine with its analgesic effects identified as a mu-receptor agonist. Due to its opioid-like stimulant effects, the potential for tramadol misuse is a public health concern. As such, the aim of this investigation is to estimate the prevalence of tramadol misuse in a s le of Iranian adolescents and to assess the relationship between tramadol misuse and other substance use. This is the first phase of a prospective survey examining the prevalence of adolescent smoking status, substances use and related factors in Ilam city, Iran. Grade 10 male and female students (n=2000) were recruited using multistage s ling. Self-administered multiple-choice questionnaires were conducted with data analysed using cross tabulations and logistic regression models. The prevalence of lifetime tramadol misuse was 4.8% (7.6% males 1.8% females). Adjusted odds ratios and confidence intervals for lifetime tramadol misusers reporting substance use during the past month were 2.2 (1.1-4.4) for alcohol, 5.0 (1.5-21.9) for cannabis, 8.9 (2.7-29.4) for ecstasy, 0.5 (0.03-7.0) for meth hetamine and 2.3 (0.7-7.4) for opium. Tramadol could be a related factor or co-factor for adolescent alcohol, cannabis and ecstasy use. We recommend future longitudinal studies to investigate the possible role of tramadol as a gateway drug in the development of substance abuse.
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.WOMBI.2017.10.007
Abstract: Fear of childbirth is a problematic mental health issue during pregnancy. But, effective interventions to reduce this problem are not well understood. To examine effective interventions for reducing fear of childbirth. The Cochrane Central Register of Controlled Trials, PubMed, Embase and PsycINFO were searched since inception till September 2017 without any restriction. Randomised controlled trials and quasi-randomised controlled trials comparing interventions for treatment of fear of childbirth were included. The standardized mean differences were pooled using random and fixed effect models. The heterogeneity was determined using the Cochran's test and I Ten studies inclusive of 3984 participants were included in the meta-analysis (2 quasi-randomized and 8 randomized clinical trials). Eight studies investigated education and two studies investigated hypnosis-based intervention. The pooled standardized mean differences of fear for the education intervention and hypnosis group in comparison with control group were -0.46 (95% CI -0.73 to -0.19) and -0.22 (95% CI -0.34 to -0.10), respectively. Both types of interventions were effective in reducing fear of childbirth however our pooled results revealed that educational interventions may reduce fear with double the effect of hypnosis. Further large scale randomized clinical trials and in idual patient data meta-analysis are warranted for assessing the association.
Publisher: Public Library of Science (PLoS)
Date: 17-10-2017
Publisher: Springer Science and Business Media LLC
Date: 04-01-2013
Abstract: Suicide, a social phenomenon, is a major health problem in most countries. Yet data relating to the role social factors play in the development of this condition are lacking, with some factors shrouded in greater ambiguity than others. As such, this review aimed to determine the prevalence of social-related factors resulting in suicide and to present these findings through meta-analyses, allowing for causes of heterogeneity to be examined. Scientific databases including PubMed and Science direct were searched using sensitive keywords. Two researchers reviewed the eligibility of studies and extracted data. Meta-regression with the Mantel-Haenszel method was conducted using a random effect model, in addition to subgroup analysis and Egger’s test. A total of 2,526 articles were retrieved through the initial search strategy, producing 20 studies from 16 provinces for analysis. The most frequent cause of attempted suicide among the 20 analyzed articles was family conflict with 32% (95% CI: 26–38). Other related factors included marital problems (26% 95% CI: 20–33), economic constrains (12% 95% CI: 8–15) and educational failures (5% 95% CI: 3–8). Results of meta-regression analysis found that s le size significantly affects heterogeneity for the factor ‘family conflict’. Social factors such as family conflicts and marital problems have a noticeable role in Iranian suicidology.
Publisher: Oxford University Press (OUP)
Date: 12-09-2018
Publisher: BMJ
Date: 05-2019
DOI: 10.1136/BMJOPEN-2018-028698
Abstract: Previous research from the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC) and others has shown that pharmacological blood pressure (BP)- lowering substantially reduces the risk of major cardiovascular events, including ischaemic heart disease, heart failure and stroke. In this new phase, the aim is to conduct in idual patient-level data (IPD) meta-analyses involving eligible BP-lowering randomised controlled trials (RCTs) to address uncertainties relating to efficacy and safety of BP-lowering treatment. RCTs investigating the effect of pharmacological BP-lowering, with a minimum of 1000 patient-years of follow-up in each trial arm, are eligible. Our systematic review identified 100 potentially eligible trials. We requested their investigators/sponsors to contribute baseline, follow-up and outcomes data. As of June 2018, the collaboration has obtained data from 49 trials (n=315 046 participants), with additional data currently in the process of being transferred from four RCTs (n=34 642 participants). In addition, data harmonisation has commenced. Scientific activities of the collaboration are overseen by the Steering Committee with input from all collaborators. Detailed protocols for in idual meta-analyses will be developed and registered on public platforms. Ethics approval has been obtained for this new and extended phase of the BPLTTC, the largest collaboration of de-identified IPD from RCTs. It offers an efficient and ethical manner of re-purposing existing data to answer clinically important questions relating to BP treatment as well as methodological questions relating to IPD meta-analyses. Among the immediate impacts will include reliable quantification of effects of treatment modifiers, such as baseline BP, age and prior disease, on both vascular and non-vascular outcomes. Analyses will further assess the impact of BP-lowering on important, but less well understood, outcomes, such as new-onset diabetes and renal disease. Findings will be published in peer-reviewed medical journals on behalf of the collaboration.
Location: Iran (Islamic Republic of)
Location: Iran (Islamic Republic of)
Location: United Kingdom of Great Britain and Northern Ireland
Location: Iran (Islamic Republic of)
Location: Iran (Islamic Republic of)
Location: Iran (Islamic Republic of)
No related grants have been discovered for Milad Nazarzadeh.