Effects on suicidal risk: Comparison of clozapine to other newer medicines indicated to treat schizophrenia or bipolar disorder

2021 ◽  
pp. 026988112110297
Author(s):  
Alberto Forte ◽  
Maurizio Pompili ◽  
Benedetta Imbastaro ◽  
Gabriele Pasquale De Luca ◽  
Martina Mastrangelo ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Confidence Intervals ◽  
Suicidal Behavior ◽  
Meta Analysis ◽  
Random Effect ◽  
Paired Comparisons ◽  
Suicidal Risk ◽  
Odds Ratios ◽  
Unique Effect ◽  
Reduce Risk

Background: Clozapine is the only treatment with regulatory-recognition of lowering suicidal risk, at least in schizophrenia patients. It remains uncertain whether such effects extend to other drugs for psychosis. Methods: We searched for reports on rates of suicidal behavior during treatment with clozapine and other modern drugs for psychosis (aripiprazole, olanzapine, risperidone, quetiapine, and ziprasidone) versus comparison or control treatments and analyzed the contrasts by random-effect meta-analysis to obtain pooled odds ratios (ORs) with 95% confidence intervals (CIs). Results: We identified 35 paired comparisons of modern drugs for psychosis versus comparison or control treatments in 18 reports. There was moderate overall superiority of all agents tested over alternatives (OR = 0.522, p = 0.004). With clozapine, this effect was large (OR = 0.229, p < 0.0001) and consistent (7/7 trials), but significant antisuicidal effects were not found with other drugs for psychosis in 28 other trials (OR = 0.941, p = 0.497). Apparent efficacy of specific agents ranked: risperidone ⩾ olanzapine ⩾ aripiprazole ⩾ ziprasidone ⩾ mixed drugs for psychosis ⩾ quetiapine, but none of these differences was significant. Conclusions: An ability of clozapine to reduce risk of suicides and attempts in schizophrenia patients appears to be a unique effect not shared with other modern medicines indicated for schizophrenia or bipolar disorder.

Abstract 3789: Nessun Dorma : Have the Risks of Rosiglitazone been Exaggerated?

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
George A Diamond ◽  
Sanjay Kaul
Keyword(s):  
Confidence Intervals ◽  
Effect Size ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Cardiovascular Death ◽  
Sensitivity Analyses ◽  
Odds Ratios ◽  
True Effect Size ◽  
Index Study ◽  
The Stability

Background A highly publicized meta-analysis of 42 clinical trials comprising 27,844 diabetics ignited a firestorm of controversy by charging that treatment with rosiglitazone was associated with a “…worrisome…” 43% greater risk of myocardial infarction ( p =0.03) and a 64% greater risk of cardiovascular death ( p =0.06). Objective The investigators excluded 4 trials from the infarction analysis and 19 trials from the mortality analysis in which no events were observed. We sought to determine if these exclusions biased the results. Methods We compared the index study to a Bayesian meta-analysis of the entire 42 trials (using odds ratio as the measure of effect size) and to fixed-effects and random-effects analyses with and without a continuity correction that adjusts for values of zero. Results The odds ratios and confidence intervals for the analyses are summarized in the Table . Odds ratios for infarction ranged from 1.43 to 1.22 and for death from 1.64 to 1.13. Corrected models resulted in substantially smaller odds ratios and narrower confidence intervals than did uncorrected models. Although corrected risks remain elevated, none are statistically significant (*p<0.05). Conclusions Given the fragility of the effect sizes and confidence intervals, the charge that roziglitazone increases the risk of adverse events is not supported by these additional analyses. The exaggerated values observed in the index study are likely the result of excluding the zero-event trials from analysis. Continuity adjustments mitigate this error and provide more consistent and reliable assessments of true effect size. Transparent sensitivity analyses should therefore be performed over a realistic range of the operative assumptions to verify the stability of such assessments especially when outcome events are rare. Given the relatively wide confidence intervals, additional data will be required to adjudicate these inconclusive results.

scholarly journals Tryptophan Catabolites in Bipolar Disorder: A Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Kaat Hebbrecht ◽  
Katrien Skorobogatov ◽  
Erik J. Giltay ◽  
Violette Coppens ◽  
Livia De Picker ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Cerebrospinal Fluid ◽  
Methodological Quality ◽  
Meta Analysis ◽  
Random Effect ◽  
Healthy Controls ◽  
Significant Difference ◽  
Subgroup Analyses ◽  
Tryptophan Catabolites

ObjectiveTryptophan catabolites (TRYCATs) are implicated in the pathophysiology of mood disorders by mediating immune-inflammation and neurodegenerative processes. We performed a meta-analysis of TRYCAT levels in bipolar disorder (BD) patients compared to healthy controls.MethodsA systematic literature search in seven electronic databases (PubMed, Embase, Web of Science, Cochrane, Emcare, PsycINFO, Academic Search Premier) was conducted on TRYCAT levels in cerebrospinal fluid or peripheral blood according to the PRISMA statement. A minimum of three studies per TRYCAT was required for inclusion. Standardized mean differences (SMD) were computed using random effect models. Subgroup analyses were performed for BD patients in a different mood state (depressed, manic). The methodological quality of the studies was rated using the modified Newcastle-Ottawa Quality assessment Scale.ResultsTwenty-one eligible studies were identified. Peripheral levels of tryptophan (SMD = -0.44; p &lt; 0.001), kynurenine (SMD = - 0.3; p = 0.001) and kynurenic acid (SMD = -.45; p = &lt; 0.001) were lower in BD patients versus healthy controls. In the only three eligible studies investigating TRP in cerebrospinal fluid, tryptophan was not significantly different between BD and healthy controls. The methodological quality of the studies was moderate. Subgroup analyses revealed no significant difference in TRP and KYN values between manic and depressed BD patients, but these results were based on a limited number of studies.ConclusionThe TRYCAT pathway appears to be downregulated in BD patients. There is a need for more and high-quality studies of peripheral and central TRYCAT levels, preferably using longitudinal designs.

scholarly journals Association between BRCA1 polymorphisms rs799917 and rs1799966 and breast cancer risk: a meta-analysis

2019 ◽  
Vol 47 (4) ◽  
pp. 1409-1416
Author(s):  
Meiming Yang ◽  
Xiaoli Du ◽  
Feng Zhang ◽  
Shifang Yuan
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Confidence Intervals ◽  
Subgroup Analysis ◽  
Meta Analysis ◽  
Recessive Model ◽  
Dominant Model ◽  
Odds Ratios

Background Several studies have reported correlations between BRCA1 polymorphisms rs799917 and rs1799966 with the risk of breast cancer (BC). However, this relationship remains controversial. Methods We conducted a meta-analysis of seven studies to assess the associations between BRCA1 rs799917 and rs1799966 and BC risk, with the aim of more accurately determining the potential correlation. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated to evaluate the correlation of rs799917 and rs1799966 with BC risk. Results There was no overall correlation between BRCA1 rs799917 and BC risk (TT vs CC: OR = 0.87, 95% CI = 0.66–1.16; CT vs CC: OR = 1.02, 95% CI = 0.89–1.15; dominant model: OR = 0.99, 95% CI = 0.88–1.11; recessive model: OR = 0.87, 95% CI = 0.65–1.16). Subgroup analysis by ethnicity also revealed no significant correlation between rs799917 and BC risk in either Asians or Caucasians. There was also no significant association between BRCA1 rs1799966 and BC risk (GG vs AA: OR = 0.70, 95% CI = 0.33–1.47; AG vs AA: OR = 0.68, 95% CI = 0.35–1.30; dominant model: OR = 0.76, 95% CI = 0.49–1.06; recessive model: OR = 0.82, 95% CI = 0.49–1.36). Conclusion BRCA1polymorphisms rs799917 and rs1799966 were not significantly associated with BC risk in this meta-analysis.

scholarly journals GSTT1 Null Genotype and Susceptibility to Children Acute Leukemia in Chinese Population: Evidence from a Meta-Analysis

2019 ◽  
Vol 18 ◽  
pp. 153303381986736
Author(s):  
De-qiang Ma
Keyword(s):  
Acute Leukemia ◽  
Confidence Intervals ◽  
Chinese Population ◽  
Southern China ◽  
Lymphoblastic Leukemia ◽  
Random Effect ◽  
Random Effect Model ◽  
Odds Ratios ◽  
Glutathione S Transferase ◽  
Childhood Acute Leukemia

Objectives: Increasing number of studies has focused on studying the relationship between glutathione S-transferase T1 polymorphism and children acute leukemia, among which discrepancies have risen. The aim of this study is to provide a more exact assessment of glutathione S-transferase T1 polymorphism and children acute leukemia among certain Chinese population. Methods: Studies were identified using PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure and Chinese Biology Medicine from beginning to July 2018. The strength of association was quantified by pooling odds ratios and 95% confidence intervals using fixed-effect or random-effect model according to the heterogeneity. Results: Overall, a positive relationship was found in null genotype of glutathione S-transferase T1 polymorphism on the risk of childhood acute leukemia among all Chinese populations (odds ratios: 1.52; 95% confidence intervals = 1.19-1.94). Similarly, consistent results were found in subgroup of Southern China (odds ratios: 1.48; 95% confidence intervals: 1.08-2.02), Northern China (odds ratios: 1.59; 95% confidence intervals: 1.09-2.33), acute lymphoblastic leukemia (odds ratios: 1.61; 95% confidence intervals: 1.19-2.17), “age > 18 years” (odds ratios: 1.59; 95% confidence intervals: 1.09-2.33), “age < 18 years” (odds ratios: 1.48; 95% confidence intervals: 1.08-2.02), and population-based studies (odds ratios: 1.60; 95% confidence intervals: 1.16-2.20). Conclusions: Collectively, finding from the current study indicated that GSTT1 null polymorphism may be susceptible on childhood acute leukemia among Chinese.

scholarly journals SMAD3 gene rs12901499 polymorphism increased the risk of osteoarthritis

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Hao-Yu Yang ◽  
Wen-Hao Hu ◽  
Tao Jiang ◽  
Hui Zhao
Keyword(s):  
Sensitivity Analysis ◽  
Knee Osteoarthritis ◽  
Family Member ◽  
Confidence Intervals ◽  
Subgroup Analysis ◽  
Meta Analysis ◽  
Hip Osteoarthritis ◽  
Odds Ratios ◽  
Increased Risk ◽  
Growing Body

A growing body of evidence suggested that smad family member 3 gene rs12901499 polymorphism was associated with the risk of osteoarthritis. However, the results of previous studies were conflicting. In the present study, we assessed whether smad family member 3 gene rs12901499 polymorphism was associated with the risk of osteoarthritis by the meta-analysis. We searched in the databases of PubMed, Embase, and CNKI. Pooled odds ratios and 95% confidence intervals were calculated. Seven papers involving 11 studies (5344 cases and 9080 controls) analyzed the association between smad family member 3 gene rs12901499 polymorphism and osteoarthritis risk. This meta-analysis confirmed that smad family member 3 gene rs12901499 polymorphism increased the risk of osteoarthritis. Stratification analysis of ethnicity found that rs12901499 polymorphism increased the risk of osteoarthritis among both Asians and Caucasians [G vs A: Asians, OR and 95%CI, 1.34(1.07, 1.69), P=0.012; Caucasians, OR and 95%CI, 1.21(1.13, 1.29), P<0.001]. In addition, subgroup analysis by type of osteoarthritis revealed that smad family member 3 gene rs12901499 polymorphism was correlated with the increased risk of hip osteoarthritis, but not associated with knee osteoarthritis. Sensitivity analysis did not draw different findings. In conclusion, this meta-analysis indicates that smad family member 3 gene rs12901499 polymorphism increased the risk of osteoarthritis.

scholarly journals The Study of Diagnostic Value of Bipolarity Index for Bipolar Disorder in China: Meta-analysis of Sensitivity and Specificity

2020 ◽  
Author(s):  
Fengli Sun ◽  
Zhu Jianfeng ◽  
Tao Hejian ◽  
Jin Weidong
Keyword(s):  
Bipolar Disorder ◽  
Predictive Value ◽  
Case Reports ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Diagnostic Value ◽  
Psychiatric Clinic ◽  
Significant Heterogeneity ◽  
Study Results

Abstract BackgroundThe diagnosis of bipolar disorder is still one of the key problems in psychiatric clinic. Although DSM-5 has made some important changes, it has not completely changed the missed diagnosis and misdiagnosis of bipolar disorder.It was very important that diagnostic scale was used in clinic.But the study results of assist diagnostic scale for bipolar disorder should been concluded and analyzed.Bipolarity index was one of assist diagnostic scale,which should be analyzed comprehensively.MethodsWe searched CBM, CNKI , WANFANG and CSSCI in Chinese to find literature from Julyr 31 2004 to July 31 2020 related to Bipolarity Index in diagnosis for bipolar disorder ,among which results such as comments, letters, reviews and case reports were excluded. The rate of sensitivity,specificity,accuracy,positive predictive value and negative predictive value in diagnosis was synthesized and discussed.ResultsA total of 1237 subjects were included in 5 studies. Random effect model is used to account for the data by Revman 5.2. The results showed that the sensitivity of BI in diagnostic was 0.93 (95% CI: 0.93–1.00), the specificity was 85% (95% CI: 0.69–0.96). the positive predict value was 74% (95% CI: 0.53–0.91).the negative predict value was 95% (95% CI: 0.81–1.00).and accuracy was 86% (95% CI: 0.77–0.93). Significant heterogeneity was detected across studies regarding these incidence estimates. ConclusionThe idea diagnostic value of BI was found. although the significant heterogeneity detected in studies.We must interpret the results with caution and also put attention to this result,which include comparison to other diagnostic scale,perfecting sue of BI in clinical psychiatry.

scholarly journals Obesity Increases the Severity and Mortality of Influenza and COVID-19: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 11 ◽  
Author(s):  
Xue Zhao ◽  
Xiaokun Gang ◽  
Guangyu He ◽  
Zhuo Li ◽  
You Lv ◽  
...  
Keyword(s):  
Systematic Review ◽  
Morbid Obesity ◽  
Risk Factor ◽  
Confidence Intervals ◽  
Web Of Science ◽  
Meta Analysis ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Systematic Search ◽  
Odds Ratios

Since December 2019, COVID-19 has aroused global attention. Studies show the link between obesity and severe outcome of influenza and COVID-19. Thus, we aimed to compare the impacts of obesity on the severity and mortality of influenza and COVID-19 by performing a meta-analysis. A systematic search was performed in MEDLINE, EMASE, ClinicalTrials.gov, and Web of Science from January 2009 to July 2020. The protocol was registered onto PROSPERO (CRD42020201461). After selection, 46 studies were included in this meta-analysis. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were analyzed. We found obesity was a risk factor for the severity and mortality of influenza (ORsevere outcome = 1.56, CI: 1.28-1.90; ORmortality = 1.99, CI: 1.15-3.46). For COVID-19, obesity was a significant risk factor only for severe outcome (OR = 2.07, CI: 1.53-2.81) but not for mortality (OR = 1.57, CI: 0.85-2.90). Compared with obesity, morbid obesity was linked with a higher risk for the severity and mortality of both influenza (OR = 1.40, CI: 1.10-1.79) and COVID-19 (OR = 3.76, CI: 2.67-5.28). Thus, obesity should be recommended as a risk factor for the prognosis assessment of COVID-19. Special monitoring and earlier treatment should be implemented in patients with obesity and COVID-19.

TNF-α and LT-α Polymorphisms and the Risk of Leukemia: A Meta-analysis

2016 ◽  
Vol 103 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Li-li Gong ◽  
Fei-fei Han ◽  
Ya-li Lv ◽  
He Liu ◽  
Zi-rui Wan ◽  
...  
Keyword(s):  
Confidence Intervals ◽  
Meta Analysis ◽  
Multivariable Analysis ◽  
Odds Ratios ◽  
Tnf Α ◽  
Subgroup Analyses

Aim The aim of this study is to investigate whether TNF-α or LT-α polymorphisms are associated with the risk of leukemia. Methods A meta-analysis was performed to examine the association between the TNF-α −308 G>A and LT-α +252 A>G polymorphisms and the incidence of leukemia. We also performed subgroup analyses based on the classification of leukemias. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the association. Results A total of 19 publications comprising 1,509 cases and 4,075 controls were selected in the study. An association between the risk of leukemia and the LT-α +252 AA genotype was found (GG + AG vs. AA, OR = 0.485, 95% CI 0.368-0.639, p = 0.000). After multivariable analysis TNF-α polymorphism showed no consistent association with leukemia. Conclusions This meta-analysis suggests that the LT-α +252 AA polymorphism is associated with the risk of leukemia.

scholarly journals Association of Immune and Inflammatory Gene Polymorphism With the Risk of IgA Nephropathy: A Systematic Review and Meta-Analysis of 45 Studies

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaonan Ding ◽  
Yan Mei ◽  
Zhi Mao ◽  
Lingling Long ◽  
Qiuxia Han ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Iga Nephropathy ◽  
Association Studies ◽  
Meta Analysis ◽  
Random Effect ◽  
Genetic Association Studies ◽  
Nucleotide Polymorphisms ◽  
Odds Ratios ◽  
Single Nucleotide ◽  
Pubmed Database

IgA nephropathy is the most prevalent primary glomerulonephritis worldwide, with identical immunopathological characteristics caused by multiple etiologies as well as influenced by geographical and ethnical factors. To elucidate the role of immunologic and inflammatory mechanisms in the susceptibility to IgA nephropathy, we explored single nucleotide polymorphisms of related molecules in the immune pathways. We searched the PubMed database for studies that involved all gene variants of molecules in the 20 immunologic and inflammatory pathways selected from the Kyoto Encyclopedia of Genes and Genomes database. The odds ratios with their corresponding 95% confidence intervals in six genetic models (allele model, dominant model, homozygote model, heterozygote model, overdominant model, and recessive model) were summarized using fixed or random effect models. Subgroup analysis was conducted based on different ethnicities with generalized odds ratios. Heterogeneity was evaluated using the Q and I2 tests. Begg’s funnel plot and Egger’s linear regression test were used to evaluating possible publication bias among the included studies, and sensitivity analysis was used to test the stability of the overall results. A total of 45 studies met our selection criteria and eight related genetic association studies were retrieved, including 320 single-nucleotide polymorphisms from 20 candidate pathways, ranging from 2000 to 2021. A total of 28,994 healthy people versus 20,600 IgA nephropathy patients were enrolled. Upon meta-analyzed results that TGFB1 (rs1800469, rs1982073, rs1800471), IL-1B (rs1143627), IL-18 (rs1946518), and TLR1 (rs5743557) showed effect with or without ethnicity difference. And 10 variants presented stable and robust related to IgA nephropathy. This research showed that genetic variants are related to the immunologic and inflammatory effects of IgA nephropathy pathogenesis. The meta-analysis results supported the previous researches, and may help deepen the understanding of pathogenesis and explore new targets for IgA nephropathy-specific immunotherapy.

scholarly journals Association between Two Common Polymorphisms and Risk of Hepatocellular Carcinoma: Evidence from an Updated Meta-Analysis

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Zhaoming Wang ◽  
Lei Zhang ◽  
Xuesong Shi ◽  
Huayu Xu ◽  
Ting Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Confidence Intervals ◽  
Meta Analysis ◽  
Asian Population ◽  
Odds Ratios ◽  
Individual Susceptibility

Background. Recent studies suggested that two common polymorphisms, miR-146a G>C and miR-196a2 C>T, may be associated with individual susceptibility to hepatocellular carcinoma (HCC). However, the results remain conflicting rather than conclusive.Object. The aim of this study was to assess the association between miR-146a G>C and miR-196a2 C>T polymorphisms and the risk of HCC.Methods. A meta-analysis of 17 studies (10938 cases and 11967 controls) was performed. Odds ratios and 95% confidence intervals were used to evaluate the strength of the association.Results. For miR-146a G>C, the variant genotypes were associated with a decreased risk of HCC (CC versus GG: OR = 0.780 and 95% CI 0.700–0.869; GC/CC versus GG: OR = 0.865 and 95% CI 0.787–0.952; CC versus GC/GG: OR = 0.835 and 95% CI 0.774–0.901). For miR-196a2 C>T, significant association was also observed (TT versus CC: OR = 0.783, 95% CI: 0.649–0.943, andP=0.010; CT versus CC: OR = 0.831, 95% CI 0.714–0.967, andP=0.017; CT/TT versus CC: OR = 0.817, 95% CI 0.703–0.949, andP=0.008).Conclusion. The two common polymorphisms miR-146a G>C and miR-196a2 C>T were associated with decreased HCC susceptibility, especially in Asian population.

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