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Effect of tocilizumab, sarilumab, and baricitinib on mortality among patients hospitalized for COVID-19 treated with corticosteroids: a systematic review and meta-analysis.
Albuquerque, AM, Eckert, I, Tramujas, L, Butler-Laporte, G, McDonald, EG, Brophy, JM, Lee, TC
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2023;(1):13-21
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Abstract
BACKGROUND Randomized controlled trials (RCT) established the mortality reduction by tocilizumab (Actemra), baricitinib (Olumiant), and sarilumab (Kevzara) in hospitalized COVID-19 patients. However, uncertainty remains about which treatment performs best in patients receiving corticosteroids. OBJECTIVES To estimate probabilities of noninferiority between baricitinib and sarilumab compared to tocilizumab in patients treated with corticosteroids. DATA SOURCES PubMed, Embase, Cochrane Library, and MedRxiv. STUDY ELIGIBILITY CRITERIA Eligible RCTs assigning hospitalized adults with COVID-19 treated with corticosteroids to tocilizumab or baricitinib or sarilumab versus standard of care or placebo (control). METHODS Reviewers independently abstracted published data and assessed study quality with the Risk of Bias 2 tool. Unpublished data, if required, were requested from authors of included studies. The outcome of interest was all-cause mortality at 28 days. PARTICIPANTS Twenty-seven RCTs with 13 549 patients were included. Overall, the risk of bias was low. Bayesian pairwise meta-analyses were used to aggregate results of each treatment versus control. The average odds ratio for mortality was 0.78 (95% credible interval [CrI]: 0.65, 0.94) for tocilizumab; 0.78 (95% CrI: 0.56, 1.03) for baricitinib; and 0.91 (95% CrI: 0.60, 1.40) for sarilumab. The certainty of evidence (GRADE) ranged from moderate to low. Bayesian meta-regressions with multiple priors were used to estimate probabilities of noninferiority (margin of 13% greater effect by tocilizumab). Compared to tocilizumab, there were ≤94% and 90% probabilities of noninferiority with baricitinib and sarilumab, respectively. RESULTS All but two studies included data with only indirect evidence for the comparison of interest. CONCLUSIONS Among hospitalized COVID-19 treated with corticosteroids, there are high probabilities that both baricitinib and sarilumab are associated with similar mortality reductions in comparison to tocilizumab.
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Treatment and prescribing trends of antihypertensive drugs in 2.7 million UK primary care patients over 31 years: a population-based cohort study.
Rouette, J, McDonald, EG, Schuster, T, Brophy, JM, Azoulay, L
BMJ open. 2022;(6):e057510
Abstract
OBJECTIVES To describe the prescribing trends of antihypertensive drugs in primary care patients and assess the trajectory of antihypertensive drug prescriptions, from first-line to third-line, in patients with hypertension according to changes to the United Kingdom (UK) hypertension management guidelines. DESIGN Population-based cohort study. SETTING AND PARTICIPANTS We used the UK Clinical Practice Research Datalink, an electronic primary care database representative of the UK population. Between 1988 and 2018, we identified all adult patients with at least one prescription for a thiazide diuretic, angiotensin-converting enzyme (ACE) inhibitor, angiotensin receptor blocker, beta-blocker or calcium channel blocker (CCB). PRIMARY AND SECONDARY OUTCOME MEASURES We estimated the period prevalence of patients with antihypertensive drug prescriptions for each calendar year over a 31-year period. Treatment trajectory was assessed by identifying patients with hypertension newly initiating an antihypertensive drug, and treatment changes were defined by a switch or add-on of a new class. This cohort was stratified before and after 2007, the year following important changes to UK hypertension management guidelines. RESULTS The cohort included 2 709 241 patients. The prevalence of primary care patients with antihypertensive drug prescriptions increased from 7.8% (1988) to 21.9% (2018) and was observed for all major classes except thiazide diuretics. Patients with hypertension initiated thiazide diuretics (36.8%) and beta-blockers (23.6%) as first-line drugs before 2007, and ACE inhibitors (39.9%) and CCBs (31.8%) after 2007. After 2007, 17.3% were not prescribed guideline-recommended first-line agents. Overall, patients were prescribed a median of 2 classes (IQR 1-2) after first-line treatment. CONCLUSION Nearly one-quarter of primary care patients were prescribed antihypertensive drugs by the end of the study period. Most patients with hypertension initiated guideline-recommended first-line agents. Not all patients, particularly females, were prescribed recommended agents however, potentially leading to suboptimal cardiovascular outcomes. Future research should aim to better understand the implication of this finding.
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Dihydropyridine Calcium Channel Blockers and Risk of Pancreatic Cancer: A Population-Based Cohort Study.
Rouette, J, McDonald, EG, Schuster, T, Brophy, JM, Azoulay, L
Journal of the American Heart Association. 2022;(24):e026789
Abstract
Background Recent studies have reported that dihydropyridine calcium channel blockers (dCCBs) may increase the risk of pancreatic cancer, but these studies had methodological limitations. We thus aimed to determine whether dCCBs are associated with an increased risk of pancreatic cancer compared with thiazide diuretics, a clinically relevant comparator. Methods and Results We conducted a new user, active comparator, population-based cohort study using the UK Clinical Practice Research Datalink. We identified new users of dCCBs and new users of thiazide diuretics between 1990 and 2018, with follow-up until 2019. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% CIs for pancreatic cancer, comparing dCCBs with thiazide diuretics. Models were weighted using standardized morbidity ratio weights based on calendar time-specific propensity scores. We also conducted secondary analyses by cumulative duration of use, time since initiation, and individual drugs and assessed for the presence of effect modification by age, sex, smoking status, body mass index, history of chronic pancreatitis, and diabetes. The cohort included 344 480 initiators of dCCBs and 357 968 initiators of thiazide diuretics, generating 3 360 745 person-years of follow-up. After a median follow-up of 4.5 years, the weighted incidence rate per 100 000 person-years was 37.2 (95% CI, 34.1-40.4) for dCCBs and 39.4 (95% CI, 36.1-42.9) for thiazide diuretics. Overall, dCCBs were not associated with an increased risk of pancreatic cancer (weighted HR, 0.93; 95% CI, 0.80-1.09). Similar results were observed in secondary analyses. Conclusions In this large, population-based cohort study, dCCBs were not associated with an increased risk of pancreatic cancer compared with thiazide diuretics. These findings provide reassurance regarding the long-term pancreatic cancer safety of these drugs.
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Diagnostic accuracy of serum (1-3)-β-D-glucan for Pneumocystis jirovecii pneumonia: a systematic review and meta-analysis.
Del Corpo, O, Butler-Laporte, G, Sheppard, DC, Cheng, MP, McDonald, EG, Lee, TC
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2020;(9):1137-1143
Abstract
BACKGROUND Pneumocystis jirovecii pneumonia (PJP) can be a life-threatening opportunistic infection in immunocompromised hosts. The diagnosis can be challenging, often requiring semi-invasive respiratory sampling. The serum 1,3-β-D-glucan (BDG) assay has been proposed as a minimally invasive test for the presumptive diagnosis of PJP. METHOD We carried out a systematic review and meta-analysis using articles in the English language published between January 1960 and September 2019. We estimated the pooled sensitivity and specificity of BDG testing using a bivariate random effects approach and compared test performance in human immunodeficiency virus (HIV) and non-HIV subgroups with meta-regression. Data from the pooled sensitivity and specificity were transformed to generate pre- and post-test probability curves. RESULTS Twenty-three studies were included. The pooled sensitivity and specificity of serum BDG testing for PJP were 91% (95%CI 87-94%) and 79% (95%CI 72-84%) respectively. The sensitivity in patients with HIV was better than in patients without (94%, 95%CI 91-96%) versus 86% (95%CI 78-91%) (p 0.02), with comparable specificity (83%, 95%CI 69-92% versus 83%, 95%CI 72-90%) (p 0.10). A negative BDG was only associated with a low post-test probability of PJP (≤5%) when the pre-test probability was low to intermediate (≤20% in non-HIV and ≤50% in HIV). CONCLUSIONS Among patients with a higher likelihood of PJP, the pooled sensitivity of BDG is insufficient to exclude infection. Similarly, for most cases, the pooled specificity is inadequate to diagnose PJP. Understanding the performance of BDG in the population being investigated is therefore essential to optimal clinical decision-making.