Risk and protective factors for cannabis, cocaine, and opioid use disorders: An umbrella review of meta-analyses of observational studies

Several meta-analyses of observational studies have addressed the association between risk and protective factors and cannabis/cocaine/opioid use disorders, but results are conflicting. No umbrella review has ever graded the credibility of this evidence (not significant/weak/suggestive/highly suggestive/convincing). We searched Pubmed-MEDLINE/PsycInfo, last search September 21, 2020. We assessed the quality of meta-analyses with the AMSTAR-2 tool. Out of 3,072 initial references, five were included, providing 19 associations between 12 putative risk/protective factors and cannabis/cocaine/opioid use disorders (cases: 4539; N=1,118,872,721). While 84% of the associations were statistically significant, none was convincing. One risk factor (smoking) had highly suggestive evidence for association with nonmedical use of prescription opioid medicines (OR=3.07, 95%CI:2.27 to 4.14). Convincing evidence emerged in sensitivity analyses on antisocial behavior and cannabis use disoder (OR 3.34, 95%CI 2.53-4.41). Remaining associations had weak evidence. The quality of meta-analyses was rated as moderate in two (40%), low in one (20%), and critically low in two (40%). Future research is needed to better profile risk/protective factors for cannabis/cocaine/opioid use disorders disorders informing preventive approaches

Efficacy and acceptability of pharmacological and non-pharmacological interventions for non-specific chronic low back pain:a protocol for a systematic review and network meta-analysis

Background: Despite the enormous financial and humanistic burden of chronic low back pain (CLBP), there is little consensus on what constitutes the best treatment options from a multitude of competing interventions. The objective of this network meta-analysis (NMA) is to determine the relative efficacy and acceptability of primary care treatments for non-specific CLBP, with the overarching aim of providing a comprehensive evidence base for informing treatment decisions. Methods: We will perform a systematic search to identify randomised controlled trials of interventions endorsed in primary care guidelines for the treatment of non-specific CLBP in adults. Information sources searched will include major bibliographic databases (MEDLINE, Embase, CENTRAL, CINAHL, PsycINFO and LILACS) and clinical trial registries. Our primary outcomes will be patient-reported pain ratings and treatment acceptability (all-cause discontinuation), and secondary outcomes will be functional ability, quality of life and patient/physician ratings of overall improvement. A hierarchical Bayesian class-based NMA will be performed to determine the relative effects of different classes of pharmacological (NSAIDs, opioids, paracetamol, anti-depressants, muscle relaxants) and non- pharmacological (exercise, patient education, manual therapies, psychological therapy, multidisciplinary approaches, massage, acupuncture, mindfulness) interventions and individual treatments within a class (e.g. NSAIDs: diclofenac, ibuprofen, naproxen). We will conduct risk of bias assessments and threshold analysis to assess the robustness of the findings to potential bias. We will compute the effect of different interventions relative to placebo/no treatment for both short- and long-term efficacy and acceptability. Discussion: While many factors are important in selecting an appropriate intervention for an individual patient, evidence for the analgesic effects and acceptability of a treatment are key factors in guiding this selection. Thus, this NMA will provide an important source of evidence to inform treatment decisions and future clinical guidelines

Environmental risk factors and biomarkers for autism spectrum disorder:an umbrella review of the evidence

Background Numerous studies have identified potential risk factors and biomarkers for autism spectrum disorder. We aimed to study the strength and validity of the suggested environmental risk factors or biomarkers of autism spectrum disorder. Methods We did an umbrella review and systematically appraised the relevant meta-analyses of observational studies. We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews for papers published between database inception and Oct 17, 2018, and screened the reference list of relevant articles. We obtained the summary effect, 95% CI, heterogeneity, and 95% prediction intervals. We examined small study effects and excess significance. We did analyses under credibility ceilings. This review is registered with PROSPERO, number CRD42018091704. Findings 46 eligible articles yielded data on 67 environmental risk factors (544 212 cases, 81 708 787 individuals) and 52 biomarkers (15 614 cases, 15 433 controls). Evidence of association was convincing for maternal age of 35 years or over (relative risk [RR] 1.31, 95% CI 1.18-1.45), maternal chronic hypertension (odds ratio [OR] 1.48, 1.29-1.70), maternal gestational hypertension (OR 1.37, 1.21-1.54), maternal overweight before or during pregnancy (RR 1.28, 1.19-1.36), pre-eclampsia (RR 1.32, 1.20-1.45), prepregnancy maternal antidepressant use (RR 1.48, 1.29-1.71), and maternal selective serotonin reuptake inhibitor (SSRI) use during pregnancy (OR 1.84, 1.60-2.11). Only two associations, maternal overweight before or during pregnancy and SSRI use during pregnancy, retained their high level of evidence under subset sensitivity analyses. Evidence from biomarkers was scarce, being supported by p values close to the significance threshold and too few cases. Interpretation Convincing evidence suggests that maternal factors, such as age and features of metabolic syndrome, are associated with risk of autism spectrum disorder. Although SSRI use during pregnancy was also associated with such risk when exposed and non-exposed groups were compared, this association could be affected by other confounding factors, considering that prepregnancy maternal antidepressant use was also convincingly associated with higher risk of autism spectrum disorder. Findings from previous studies suggest that one possible confounding factor is underlying maternal psychiatric disorders. Copyright (C) 2019 Elsevier Ltd. All rights reserved.Funding Agencies|Health Education England [ICA-CL-2017-03-001]; National Institute for Health Research (NIHR) [ICA-CL-2017-03-001]; NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust; Maudsley Charity; Kings College London; NIHR South London Collaboration for Leadership in Applied Health Research and Care</p

Incidence of Capillary Leak Syndrome as an Adverse Effect of Drugs in Cancer Patients: A Systematic Review and Meta-Analysis

Capillary leak syndrome (CLS) is a rare disease with profound vascular leakage, which can be associated with a high mortality. There have been several reports on CLS as an adverse effect of anti-cancer agents and therapy, but the incidence of CLS according to the kinds of anti-cancer drugs has not been systemically evaluated. Thus, the aim of our study was to comprehensively meta-analyze the incidence of CLS by different types of cancer treatment or after bone marrow transplantation (BMT). We searched the literatures (inception to July 2018) and among 4612 articles, 62 clinical trials (studies) were eligible. We extracted the number of patients with CLS, total cancer patients, name of therapeutic agent and dose, and type of cancer. We performed a meta-analysis to estimate the summary effects with 95% confidence interval and between-study heterogeneity. The reported incidence of CLS was categorized by causative drugs and BMT. The largest number of studies reported on CLS incidence during interleukin-2 (IL-2) treatment (n = 18), which yielded a pooled incidence of 34.7% by overall estimation and 43.9% by meta-analysis. The second largest number of studies reported on anti-cluster of differentiation (anti-CD) agents (n = 13) (incidence of 33.9% by overall estimation and 35.6% by meta-analysis) or undergoing BMT (n = 7 (21.1% by overall estimation and 21.7% by meta-analysis). Also, anti-cancer agents, including IL-2 + imatinib mesylate (three studies) and anti-CD22 monoclinal antibodies (mAb) (four studies), showed a dose-dependent increase in the incidence of CLS. Our study is the first to provide an informative overview on the incidence rate of reported CLS patients as an adverse event of anti-cancer treatment. This meta-analysis can lead to a better understanding of CLS and assist physicians in identifying the presence of CLS early in the disease course to improve the outcome and optimize management

Sleep insufficiency and incident diabetes mellitus among indigenous and minority populations in Greece

Objective: To investigate the potential association between sleep pathology and diabetes mellitus (DM) using self-reported questionnaires. Material and Methods: 957 adults aged between 19 and 86 years old were enrolled in this cross-sectional study. Multistage stratified cluster sampling was used and subjects were classified into three groups [short (8h) sleep duration]. Individuals were classified as diabetics if they responded positively to the questions: “Have you ever been told that you are diabetic or have high blood sugar by a health professional?” or “Are you on antidiabetic medication?”. Sleep quality, utilizing Epworth sleepiness scale, Athens insomnia scale, Pittsburgh sleep quality index and Berlin questionnaire, was also examined. Results: DM prevalence was higher among expatriated and Muslim Greeks (23.1% and 18.7%, respectively) compared to indigenous Greek Christians (4.4%). DM prevalence was significantly associated with short sleep duration (aOR=2.82, p<0.001), excessive daytime sleepiness (aOR=2.09, p=0.019) and poor sleep quality (aOR=2.56, p<0.001), while its relation with insomnia (aOR=1.63, p=0.065) and risk for obstructive sleep apnea (aOR=1.53, p=0.080) were of marginal statistical significance. Conclusion: This study indicates an association between sleep quantity, quality and DM and supports early pharmacological and cognitive behavioral interventions on sleep disturbances in order to reduce the burden of DM with increased focus on minority population needs

An umbrella review of candidate predictors of response, remission, recovery, and relapse across mental disorders

We aimed to identify diagnosis-specific/transdiagnostic/transoutcome multivariable candidate predictors (MCPs) of key outcomes in mental disorders. We conducted&nbsp;an umbrella review (protocol&nbsp; link ), searching MEDLINE/Embase (19/07/2022), including systematic reviews of studies reporting on MCPs of response, remission, recovery, or relapse, in DSM/ICD-defined mental disorders. From published predictors, we filtered MCPs, validating MCP criteria. AMSTAR2/PROBAST measured quality/risk of bias of systematic reviews/individual studies. We included 117 systematic reviews, 403 studies, 299,888 individuals with mental disorders, testing 796 prediction models. Only 4.3%/1.2% of the systematic reviews/individual studies were at low risk of bias. The most frequently targeted outcome was remission (36.9%), the least frequent was recovery (2.5%). Studies mainly focused on depressive (39.4%), substance-use (17.9%), and schizophrenia-spectrum (11.9%) disorders. We identified numerous MCPs within disorders for response, remission and relapse, but none for recovery. Transdiagnostic MCPs of remission included lower disease-specific symptoms (disorders = 5), female sex/higher education (disorders = 3), and&nbsp;quality of life/functioning (disorders = 2). Transdiagnostic MCPs of relapse included higher disease-specific symptoms (disorders = 5), higher depressive symptoms (disorders = 3), and younger age/higher anxiety symptoms/global illness severity/ number of previous episodes/negative life events (disorders = 2). Finally, positive trans-outcome MCPs for depression included less negative life events/depressive symptoms (response, remission, less relapse), female sex (response, remission) and better functioning (response, less relapse); for schizophrenia, less positive symptoms/higher depressive symptoms (remission, less relapse); for substance use disorder, marital status/higher education (remission, less relapse). Male sex, younger age, more clinical symptoms and comorbid mental/physical symptoms/disorders were poor prognostic factors, while positive factors included social contacts and employment, absent negative life events, higher education, early access/intervention, lower disease-specific and comorbid mental and physical symptoms/conditions, across mental disorders. Current data limitations include high risk of bias of studies and extraction of single predictors from multivariable models. Identified MCPs can inform future development, validation or refinement of prediction models of key outcomes in mental disorders

Risk and protective factors for personality disorders: an umbrella review of published meta-analyses of case-control and cohort studies

The putative risk/protective factors for several personality disorders remain unclear. The vast majority of published studies has assessed personality characteristics/traits rather than disorders. Thus, the current umbrella review of meta-analyses (MAs) aims to systematically assess risk or protective factors associated with personality disorders. We searched PubMed–MEDLINE/PsycInfo databases, up to August 31, 2020. Quality of MAs was assessed with AMSTAR-2, while the credibility of evidence for each association was assessed through standard quantitative criteria. Out of 571 initial references, five meta-analyses met inclusion criteria, encompassing 56 associations of 26 potential environmental factors for antisocial, dependent, borderline personality disorder, with a median of five studies per association, and median 214 cases per association. Overall, 35 (62.5%) of the associations were nominally significant. Six associations met class II (i.e., highly suggestive) evidence for borderline personality disorder, with large effect sizes involving childhood emotional abuse (OR = 28.15, 95% CI 14.76–53.68), childhood emotional neglect (OR = 22.86, 95% CI 11.55–45.22), childhood any adversities (OR = 14.32, 95% CI 10.80–18.98), childhood physical abuse (OR = 9.30, 95% CI 6.57–13.17), childhood sexual abuse (OR = 7.95, 95% CI 6.21–10.17), and childhood physical neglect (OR = 5.73, 95% CI 3.21–10.21), plus 16 further associations supported by class IV evidence. No risk factor for antisocial or dependent personality disorder was supported by class I, II, and III, but six and seven met class IV evidence, respectively. Quality of included meta-analyses was rated as moderate in two, critically low in three. The large effect sizes found for a broad range of childhood adversities suggest that prevention of personality disorders should target childhood-related risk factors. However, larger cohort studies assessing multidimensional risk factors are needed in the field

Fatores de risco de transtornos alimentares: revisão guarda-chuva de metanálises publicadas

Objetivo: Graduar as evidências sobre fatores de risco de transtornos alimentares (anorexia nervosa, bulimia nervosa e transtorno de compulsão alimentar periódica) com o método de revisão guarda-chuva. Métodos: Trata-se de revisão sistemática de estudos observacionais sobre fatores de risco de transtornos alimentares publicados no PubMed, PsycInfo, e Embase até 11 de dezembro de 2019. Recalculamos metanálises de efeitos aleatórios, heterogeneidade, efeito de estudo pequeno, viés de excesso de significância e intervalo de confiança de 95% e graduamos evidências significativas (p < 0,05) de convincentes a fracas, conforme os critérios estabelecidos. A qualidade foi avaliada com a ferramenta Assessment of Multiple Systematic Reviews 2 (AMSTAR-2). Resultados: Foram incluídas 9 das 2.197 metanálises, as quais apresentavam evidências de 50 fatores de risco, 29.272 sujeitos com transtornos alimentares e 1.679.385 controles. Embora não houvesse associação com evidências convincentes, evidências altamente sugestivas apoiaram a associação entre abuso sexual infantil e bulimia nervosa (k = 29, 1.103 casos com distúrbios alimentares, 8.496 controles, RC, 2,73, IC95% 1,96-3.79, p = 2,1x10-9, qualidade AMSTAR-2 moderada) e entre vitimização por provocação relacionada à aparência e quaisquer transtornos alimentares (k = 10, 1.341 casos com transtornos alimentares, 3.295 controles, RC 2,91, IC95% 2,05-4,12, p = 1,8x10-9, qualidade AMSTAR-2 moderada). Evidências sugestivas, fracas ou nenhuma evidência sustentaram 11, 29 e 8 associações, respectivamente. Conclusões: Evidência mais confiáveis indicam que eventos traumáticos e estressantes precoces são fatores de risco de transtornos alimentares. São necessários estudos de coorte colaborativos prospectivos maiores para identificar fatores de risco de transtornos alimentares, especialmente a anorexia nervos

Association between sleep insufficiency and dyslipidemia: a cross-sectional study among Greek adults in the primary care setting

Objective: To investigate the potential association between sleep insufficiency and dyslipidemia (DL) in the primary care setting using self-reported questionnaires. Material and Methods: 957 adults aged between 19 and 86 years old from the rural area of Thrace, Greece were enrolled in this cross-sectional study. Multistage stratifed cluster sampling was used and the subjects were classifed into three groups according to sleep duration [short (8h) sleep duration]. DL was defined by a positive response to the question “Have you ever been told by a doctor or health professional that your blood cholesterol or triglyceride levels were high?”, or if they were currently taking antilipidemic agents. Sleep quality, utilizing Epworth sleepiness scale, Athens insomnia scale, Pittsburgh sleep quality index and Berlin questionnaire, was also examined. Results: DL prevalence was significantly associated with short sleep duration (aOR=2.18, p<0.001) and insomnia (aOR=1.43, p=0.050), while its relation with poor sleep quality (aOR=1.31, p=0.094) and risk for obstructive sleep apnea (aOR=1.32, p=0.097) were of marginal statistical significance. Concerning insomnia subtypes, DL was significantly associated with difficulties maintaining sleep (aOR=2.99, p<0.001) and early morning awakenings (aOR=1.38, p=0.050), but not difficulties initiating sleep (aOR=1.18, p=0.328). Conclusion: This study reveals an association between sleep pathology and DL. Thus, early pharmacological and cognitive or behavioral interventions that improve sleep are deemed necessary in order to decrease DL burden

Global burden of primary liver cancer and its association with underlying aetiologies, sociodemographic status, and sex differences from 1990–2019: A DALY-based analysis of the Global Burden of Disease 2019 study

Background/Aims Global distribution of dominant liver cancer aetiologies has significantly changed over the past decades. This study analyzed the updated temporal trends of liver cancer aetiologies and sociodemographic status in 204 countries and territories from 1990 to 2019. Methods The Global Burden of Disease 2019 report was used for statistical analysis. In addition, we performed stratification analysis to five quintiles using sociodemographic index and 21 geographic regions. Results The crude numbers of liver cancer disease-adjusted life years (DALYs) and deaths significantly increased during the study period (DALYs; 11,278,630 in 1990 and 12,528,422 in 2019, deaths; 365,215 in 1990 and 484,577 in 2019). However, the Age-standardized DALY and mortality rates decreased. Hepatitis B virus (HBV) remains the leading cause of liver cancer DALYs and mortality, followed by hepatitis C virus (HCV), alcohol consumption, and non-alcoholic steatohepatitis/non-alcoholic fatty liver disease (NASH/NAFLD). Although Age-standardized DALY and mortality rates of liver cancer due to HBV and HCV have decreased, the rates due to alcohol consumption and NASH/NAFLD have increased. In 2019, the population of the East Asia region had the highest Age-standardized DALY and mortality rates, followed by high-income Asia-Pacific and Central Asia populations. Although East Asia and high-income Asia-Pacific regions showed a decrease during the study period, Age-standardized DALY rates increased in Central Asia. High-income North American and Australasian populations also showed a significant increase in Age-standardized DALY. Conclusions Liver cancer remains an ongoing global threat. The burden of liver cancer associated with alcohol consumption and NASH/NAFLD is markedly increasing and projected to continuously increase