scholarly journals A meta-analysis of controlled studies comparing the association between clozapine and other antipsychotic medications and the development of neutropenia

2019 ◽  
Vol 53 (5) ◽  
pp. 403-412 ◽  
Author(s):  
Nicholas Myles ◽  
Hannah Myles ◽  
Shelley Xia ◽  
Matthew Large ◽  
Robert Bird ◽  
...  

Background: In most countries, clozapine can only be prescribed with regular monitoring of white blood cell counts because of concerns that clozapine has a stronger association with neutropenia than other antipsychotics. However, this has not been previously demonstrated conclusively with meta-analysis of controlled studies. Methods: The aim of this study was to assess the strength of the association between clozapine and neutropenia when compared to other antipsychotic medications by a meta-analysis of controlled studies. An electronic search of Medline (1948–2018), PsycINFO (1967–2018) and Embase (1947–2018) using search terms (clozapine OR clopine OR clozaril OR zaponex) AND (neutropenia OR agranulocytosis) was undertaken. Random-effects meta-analysis using Mantel–Haenszel risk ratio was used to assess the strength of the effect size. Results: We located 20 studies that reported rates of neutropenia associated with clozapine and other antipsychotic medications. The risk ratio was not significantly increased in clozapine-exposed groups compared to exposure to other antipsychotic medications (Mantel–Haenszel risk ratio = 1.45, 95% confidence interval = [0.87, 2.42]). This also applied to severe neutropenia (absolute neutrophil count < 500 per µL) when compared to other antipsychotics (Mantel–Haenszel risk ratio = 1.65, 95% confidence interval = [0.58, 4.71]). The relative risk of neutropenia associated with clozapine exposure was not significantly associated with any individual antipsychotic medication. Conclusion: Data from controlled trials do not support the belief that clozapine has a stronger association with neutropenia than other antipsychotic medications. This implies that either all antipsychotic drugs should be subjected to haematological monitoring or monitoring isolated to clozapine is not justified.

Author(s):  
Sohrab Amiri ◽  
Sepideh Behnezhad

Background and objective Depression is a common mental disorder that leads to undesirable consequences. The study of the role of depression in disability pension can provide valuable insights. This study was conducted with the goal of systematic review and meta-analysis of the relationship between depression and disability pension. Methods PubMed, Scopus, PsycInfo, and Google Scholar databases were systematically searched until March 2018. Fifteen prospective cohort studies were selected and included in the meta-analysis. The random-effects method was used to combine the studies. Subgroup analysis was performed, and publication bias was also examined. Results Depression was a risk factor for disability pension (pooled risk ratio =1.68 and 95% confidence interval = 1.50–1.88). In men, pooled risk ratio was 1.82 for the effect of depression on the risk of disability pension (95% confidence interval = 1.45–2.28). In women, pooled risk ratio was 1.62 (95% confidence interval = 1.31–2.02). The results showed that there is publication bias. Conclusions Depression is a factor for retirement due to disability. Therefore, the prevention and treatment of depression can reduce socioeconomic and psychological consequences imposed on society.


2017 ◽  
Vol 52 (5) ◽  
pp. 415-424 ◽  
Author(s):  
Alby Elias ◽  
Vivek H Phutane ◽  
Sandy Clarke ◽  
Joan Prudic

Objective: Acute course of electroconvulsive therapy is effective in inducing remission from depression, but recurrence rate is unacceptably high following termination of electroconvulsive therapy despite continued pharmacotherapy. Continuation electroconvulsive therapy and maintenance electroconvulsive therapy have been studied for their efficacy in preventing relapse and recurrence of depression. The purpose of this meta-analysis was to examine the efficacy of continuation electroconvulsive therapy and maintenance electroconvulsive therapy in preventing relapse and recurrence of depression in comparison to antidepressant pharmacotherapy alone. Methods: We searched MEDLINE, Embase, PsycINFO, clinicaltrials.gov and Cochrane register of controlled trials from the database inception to December 2016 without restriction on language or publication status for randomized trials of continuation electroconvulsive therapy and maintenance electroconvulsive therapy. Two independent Cochrane reviewers extracted the data in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews and meta-analyses. The risk of bias was assessed using four domains of the Cochrane Collaboration Risk of Bias Tool. Outcomes were pooled using random effect model. The primary outcome was relapse or recurrence of depression. Results: Five studies involving 436 patients were included in the meta-analysis. Analysis of the pooled data showed that continuation electroconvulsive therapy and maintenance electroconvulsive therapy, both with pharmacotherapy, were associated with significantly fewer relapses and recurrences than pharmacotherapy alone at 6 months and 1 year after a successful acute course of electroconvulsive therapy (risk ratio = 0.64, 95% confidence interval = [0.41, 0.98], p = 0.04, risk ratio = 0.46, 95% confidence interval = [0.21, 0.98], p = 0.05, respectively). There was insufficient data to perform a meta-analysis of stand-alone continuation electroconvulsive therapy or maintenance electroconvulsive therapy beyond 1 year. Conclusion: There are only a few randomized trials of continuation electroconvulsive therapy and maintenance electroconvulsive therapy. The preliminary and limited evidence suggests the modest efficacy of continuation electroconvulsive therapy and maintenance electroconvulsive therapy with concomitant pharmacotherapy in preventing relapse and recurrence of depressive episodes for 1 year after the remission of index episode with the acute course of electroconvulsive therapy.


Lupus ◽  
2019 ◽  
Vol 28 (3) ◽  
pp. 334-346 ◽  
Author(s):  
K M Thong ◽  
T M Chan

Objectives Infection is an important concern in lupus nephritis treatment, but few studies have focused on this complication. Available data suggest marked variation in occurrence and outcome. This meta-analysis and review aims to provide an overview of infective complications, focusing on the risk factors and outcomes. Methods Original articles on lupus nephritis Class III/IV/V published in the period January 1980 to December 2016 were identified from the Pubmed/Medline electronic database. Meta-analysis of randomized controlled trials was performed to investigate total and serious infections at different phases of treatment and their associated factors. A descriptive review that included all studies was also performed, providing details on the types of infection, infection-related mortality, and potential impact of different eras on infection rates. Results A total of 56 studies (32 randomized controlled trials) were included. The incidence rates of overall and serious infections were higher during the induction than maintenance phase of therapy, with serious infections occurring at 8.2–50 and 3.5 per 100 patient-years, respectively. Recent data, predominantly from Asia, suggested lower rates of overall infections with induction regimens that included tacrolimus compared with mycophenolate (risk ratio 0.50, 95% confidence interval 0.33–0.76, p = 0.001). Mycophenolate as induction treatment was associated with lower overall infection risks than cyclophosphamide in non-Asians (risk ratio 0.60, 95% confidence interval 0.48–0.75, p < 0.001). The rates of serious infections were 4.1–25% in Asian and 4.4–8.5% in non-Asian countries; with infection-related mortality rates of 0–6.7% in Asian, compared to 0–2.1% in non-Asian locations. Conclusions Infection remains a serious complication during treatment of lupus nephritis, but the reported rates and outcomes varied markedly. Mycophenolate was associated with lower infection risk than cyclophosphamide in non-Asians. Infection-related deaths appeared more common in Asian patients.


2019 ◽  
pp. 102490791986424
Author(s):  
Peiyun Peng ◽  
Yunfeng Xia

Introduction: Pentoxifylline may be an important approach to treat neonatal sepsis. However, its use has not been well established. We conduct a systematic review and meta-analysis to evaluate the efficacy of pentoxifylline treatment for neonatal sepsis. Methods: PubMed, Embase, and the Cochrane Central Register of Controlled Trials are searched. Randomized controlled trials assessing the influence of pentoxifylline treatment on neonatal sepsis are included. Two investigators independently have searched articles, extracted data, and assessed the quality of included studies. This meta-analysis is performed using the random-effect model. Results: Seven randomized controlled trials involving 439 patients are included in the meta-analysis. Compared with control intervention for neonatal sepsis, pentoxifylline treatment is associated with reduced hospital stay (standard mean differences = −0.61; 95% confidence interval = −0.93 to −0.29; p = 0.0002) and metabolic acidosis (risk ratio = 0.38; 95% confidence interval = 0.22 to 0.66; p = 0.0006), but has no remarkable impact on mortality (risk ratio = 0.59; 95% confidence interval = 0.30 to 1.16; p = 0.13), serum tumor necrosis factor-α (standard mean differences = −0.38; 95% confidence interval = −1.29 to 0.52; p = 0.41), serum C-reactive protein (standard mean differences = −0.25; 95% confidence interval = −0.92 to 0.42; p = 0.47), plasma interleukin-6 (standard mean differences = −0.13; 95% confidence interval = −0.41 to 0.15; p = 0.37), disseminated intravascular coagulopathy (risk ratio = 0.55; 95% confidence interval = 0.25 to 1.21; p = 0.14), and oliguria/anuria (risk ratio = 0.77; 95% confidence interval = 0.28 to 2.16; p = 0.62). Conclusion: Pentoxifylline treatment may be associated with reduced mortality and hospital stay in neonatal sepsis with caution.


2016 ◽  
Vol 28 (7) ◽  
pp. 636-650 ◽  
Author(s):  
Mansour Farahani ◽  
Holly Mulinder ◽  
Alexander Farahani ◽  
Richard Marlink

The advent of antiretroviral therapy has significantly improved AIDS-related morbidity and mortality. Yet, among people living with HIV, deaths due to non-AIDS-defining illnesses have been on the rise. The objective of this study was to provide information about the global prevalence and distribution of non-AIDS causes of death in the last ten years among people living with HIV receiving antiretroviral therapy, by income levels of countries. We used broad search terms in Google Scholar, PubMed, and EMBASE to identify all studies that investigated the cause of death among people living with HIV receiving antiretroviral therapy, published after January 1, 2005. References were also identified from review articles and reference lists. Inclusion criteria were English language, the study’s end date was after 2005, all patients were HIV-positive, at least two-thirds of the patients were receiving antiretroviral therapy, at least one patient died of non-AIDS causes of death. Titles, abstracts, and articles were reviewed by at least two independent readers. Of 2951 titles identified in our original search, 151 articles were selected for further screening. We identified 19 studies meeting our full criteria, with patients from 55 different nations. Pooled non-AIDS causes of death prevalence estimates in high-income countries were 53.0% (95% confidence interval, 43.6–62.3), in developing countries 34.0% (95% confidence interval, 20.3–49.1), and in sub-Saharan countries 18.5% (95% confidence interval, 13.8–23.7). Statistically significant variation was noted within and between categories. Our findings show that a significant number of people living with HIV across the world die from cardiovascular disease, non-AIDS malignancies, and liver disease. There is a global need for further scrutiny in all regions to improve preventive measures and early detection according to distinct causes of death patterns.


Author(s):  
Erpeng Yang ◽  
Mingjing Wang ◽  
Ziqing Wang ◽  
Yujin Li ◽  
Xueying Wang ◽  
...  

AbstractTo assess the effects between MPL and JAK2V617F on the thrombosis risk and peripheral blood cell counts in patients with essential thrombocythemia (ET), we identified eligible studies from PubMed, Embase, and the Cochrane Library. Seven studies were ultimately included in this meta-analysis. All studies reported the peripheral blood cell counts of ET patients, and three of them reported the eligible thrombotic events. In comparing the effect of MPL versus JAK2V617F on thrombosis, 1257 ET patients (73 MPL + and 1184 JAK2V617F +) were included. MPL-positive (MPL +) ET patients had a higher risk of thrombosis than JAK2V617F-positive (JAK2V617F +) ET patients [RR = 1.80 (1.08–3.01), P = 0.025]. And 3453 ET patients (138 MPL + and 3315 JAK2V617F +) were included in the comparison of peripheral blood cell counts. Platelet counts of MPL + ET patients were higher than that of JAK2V617F + ET patients [WMD = 81.18 (31.77–130.60), P = 0.001]. MPL + ET patients had lower hemoglobin [WMD =  − 11.66 (− 14.32 to − 9.00), P = 0.000] and white blood cell counts [WMD =  − 1.01 (− 1.47 to − 0.56), P = 0.000] than JAK2V617F + ET patients. These findings indicate that the MPL mutation is a high-risk factor for thrombosis in ET patients, and it may be rational to include MPL mutation in the revised IPSET as a criterion for thrombosis prediction scores. And given the differences in peripheral blood, it is necessary to further study whether MPL + ET patients differ from JAK2V617F + ET patients in bleeding and survival.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Shariff ◽  
R Doshi ◽  
I Pedreira Vaz ◽  
D Adalja ◽  
A Krishnan ◽  
...  

Abstract Introduction Cardiogenic shock is linked with eminent morbidity and mortality despite advances in treatment modality. Adjuvant treatment modalities to provide mechanical haemodynamic support in the form of intra-aortic balloon pump (IABP) or Impella are being used among patients with cardiogenic shock. The Impella prunes left ventricular preload, whereas, IABP persuades after load reduction and both contribute to improved cardiac output. A few underpowered randomised control trials (RCTs) and observational studies compared short term mortality benefit of Impella juxtaposed to IABP among patients with cardiogenic shock. Purpose A meta-analysis of RCTs and observational studies researching the short-term mortality in cardiogenic shock comparing Impella to IABP was executed. Methods The databases PubMed, EMBASE and Cochrane were searched systematically to identify relevant RCTs and observational studies contrasting Impella to IABP and reporting 30-days mortality as outcomes. The search terms used were “Impella”, “IAPB”, “intra-aortic balloon pump” and all word variations were utilised. The search was conducted from the debut of the databases up to January 2020. Two reviewers independently and in tandem performed data screening and extraction from identified articles. Inverse variance method with Paule-Mandel estimator for tau2 and Hartung-Knapp adjustment was used to calculate Risk Ratio with 95% confidence interval. Heterogeneity was assessed using I2 statistics. Furthermore, we calculated the 95% predictive interval for the pooled estimate. All statistical analysis for this meta-analysis was carried out using R statistical software version 3.6.2 using the package meta ( ). Additionally, Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria were used to assess the certainty of evidence. Results Five studies constituting 728 patients were included in the final analysis. Two were RCTs (ISAR-SHOCK trial and IMPRESS in Severe Shock trial), one study was a propensity score matched observational study and two were unmatched observational studies. There was no difference in the risk of 30-days mortality in patients treated with Impella as compared to IABP [Risk Ratio: 0.97, 95% confidence interval: 0.66–1.41, I2: 32%]. To account for the heterogeneity, we calculated 95% predictive interval: 0.46–2.02. Thus, very low certainty of evidence concluded no difference in the risk of 30-days mortality among cardiogenic shock patients treated with Impella in opposition to IABP. Conclusion This meta-analysis comparing Impella juxtaposed with IABP demonstrated no difference in the risk of 30-days mortality among patients with cardiogenic shock. 30-days Mortality Funding Acknowledgement Type of funding source: None


Author(s):  
Chawan Kritsanaviparkporn ◽  
Phoomphut Sangaphunchai ◽  
Arucha Treesirichod

Background: Topical moisturizer is recommended for atopic dermatitis. Aims: The aim of the study was to investigate the knowledge gap regarding the efficacy of moisturizer in young patients. Methods: A systematic review and meta-analysis were conducted on randomised controlled trials comparing participant’s ≤15 years with atopic dermatitis, receiving either topical moisturizer or no moisturizer treatment. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. Results: Six trials were included (intervention n= 436; control n= 312). Moisturizer use extended time to flare by 13.52 days (95% confidence interval 0.05–26.99, I2 88%). Greater reduction in risk of relapse was observed during the first month of latency (pooled risk ratio 0.47, 95% confidence interval 0.31–0.72, I2 28%) compared to the second and third months (pooled risk ratio 0.65, 95% confidence interval 0.47–0.91, I2 35% and pooled risk ratio 0.63, 95% confidence interval 0.47–0.83, I2 33%, respectively).Treated patients were 2.68 times more likely to experience a three–six months remission (95% confidence interval1.18–6.09, I2 56%). Moisturizer minimally improved disease severity and quality of life. Limitations: There is a dire need to conduct randomised controlled trialswith more robust and standardised designs. Conclusion: Moisturizer benefits young patients with atopic dermatitis. However, more research is needed to better estimate its efficacy.


2020 ◽  
pp. 145749692095783
Author(s):  
E. Ekman ◽  
K. Lehtimäki ◽  
J. Syvänen ◽  
M. Saltychev

Background and Aims: To evaluate evidence on the superiority of plate fixation over intramedullary nail fixation in the treatment of distal tibial fractures regarding functional outcomes and complication rates. Material and Methods: Cochrane Controlled Trials Register, Medline, Embase, CINAHL, Scopus, and Web of Science databases were searched in December 2019. The risk of systematic bias was assessed according to the Cochrane Collaboration’s domain-based evaluation framework. Results: The search resulted in 514 records, the final sample included 10 randomized controlled trials (782 patients). There were statistically significant differences in operating time (−11.2, 95% confidence interval: −16.3 to −6.1 min), time to partial weight bearing (−0.96, 95% confidence interval: −1.8 to −0.1 weeks), time to full weight bearing (−2.2, 95% confidence interval: −4.32 to −0.01 weeks), the rates of deep infections (risk ratio = 0.37, 95% confidence interval: 0.19 to 0.69), and the rates of soft-tissue complications (risk ratio = 0.52, 95% confidence interval: 0.33 to 0.82) favoring intramedullary nail. Intraoperative blood loss (127.2, 95% confidence interval: 34.7 to 219.7 mL) and postoperative knee pain and stiffness (relative risk = 5.6, 95% confidence interval: 1.4–22.6) showed significant differences favoring plate fixation. When combining all complication rates, the difference was risk ratio = 0.77 (95% confidence interval: 0.63 to 0.95) favoring intramedullary nail. No significant differences in radiation time, length of incision, length of hospital stay, time to return to work, time to union, the rates of healing complications or secondary procedures, ankle pain or stiffness, or functional scores were found. Conclusion: This meta-analysis suggests that intramedullary nail might be slightly superior in reducing postoperative complications and result in slightly faster healing when compared to plate fixation.


2017 ◽  
Vol 24 (6) ◽  
pp. 412-423 ◽  
Author(s):  
T Christopher Bond ◽  
Erika Szabo ◽  
Susan Gabriel ◽  
Jean Klastersky ◽  
Omar Tomey ◽  
...  

Background Granulocyte colony-stimulating factors are effective at reducing the risk and duration of neutropenia. The current meta-analysis compared the neutropenia-related efficacy and safety of lipegfilgrastim to those of pegfilgrastim and filgrastim. Methods Embase was searched for trials examining the efficacy/safety of lipegfilgrastim, pegfilgrastim, or filgrastim. Outcomes included febrile neutropenia, severe neutropenia, duration of severe neutropenia, time to recovery of absolute neutrophil count, and incidence of bone pain. Direct comparisons were made using random-effects models. No trials directly compared lipegfilgrastim and filgrastim. Indirect comparisons were made between lipegfilgrastim and filgrastim with pegfilgrastim as the common comparator. Results This meta-analysis included a total of 5769 patients from 24 studies. Over all cycles, lipegfilgrastim showed a lower, nonsignificant risk of febrile neutropenia compared with pegfilgrastim. Lipegfilgrastim has a lower risk of febrile neutropenia versus filgrastim but was also not statistically significant. The risk ratio for severe neutropenia in cycle 1 was 0.80, a 20% reduction in favor of lipegfilgrastim. For cycles 2–4, the risk ratio was 0.53 (0.35, 0.79) for lipegfilgrastim versus pegfilgrastim. The risk of severe neutropenia in cycles 2–4 was also significantly lower for lipegfilgrastim (risk ratio 0.45, 0.27, 0.75, respectively). No significant differences were found for febrile neutropenia and severe neutropenia in cycle 1. However, in cycles 2–4, lipegfilgrastim was associated with significant and clinically meaningful reductions in risk of severe neutropenia versus either pegfilgrastim or filgrastim. Conclusions Compared with pegfilgrastim or filgrastim, lipegfilgrastim has a statistically significantly lower absolute neutrophil count recovery time; however, differences in duration of severe neutropenia and bone pain were nonsignificant.


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