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Background: Alcohol use is an important risk factor for suicidal behavior, with a heightened risk found among women. The objective of this study is to determine the gender-specific risk of suicidal behaviors (suicide attempt and death by suicide) for different levels and dimensions of alcohol use—i.e., for (1) average alcohol volume consumed, (2) binge drinking, and (3) individuals with an alcohol use disorder. Methods: We will systematically search the available literature for primary studies on the risk relationships specified above. Using a predetermined set of keywords, a comprehensive systematic literature search will be conducted in the following electronic databases: Embase, PsycINFO, PubMed, and Web of Science. The basic inclusion criteria will be (1) an original, quantitative (cohort, case–control or cross-sectional) study; with (2) a measure of risk of at least one dimension of our alcohol exposures in relation to at least one of our outcomes of interest (suicide attempt or death by suicide), and its corresponding measure of variability is reported (or sufficient data to calculate these); and (3) estimates of risk stratified by gender. Studies (1) that use only qualitative labels of alcohol use, and (2) where suicide attempt and non-suicidal self-harm cannot be disaggregated will be excluded. There will be no restrictions on language, geographical region, or year of publication. Two reviewers will independently perform the search and systematic assessment of each identified study and subsequent extraction of data. Categorical random-effects meta-analyses will be conducted to obtain gender-specific pooled risk estimates. Risk of bias will be assessed using the Risk of Bias In Non-randomised Studies—of Interventions tool and the Grading of Recommendations Assessment, Development and Evaluation approach will be used to rate the quality of evidence. Discussion: This study will synthesize all available data on the gender-specific relationship between various dimensions of alcohol use and suicidal behavior simultaneously in a coherent framework. We will provide risk estimates with the detail needed to better understand the respective risk relationships and appreciate the burden of alcohol-attributable suicide. Systematic review registration: PROSPERO CRD42022320918. [ABSTRACT FROM AUTHOR]

Reduction of long-term mortality risk, an important clinical outcome for people in alcohol dependence treatment, can rarely be established in randomized controlled trials (RCTs). We calculated the reduction in all-cause mortality risk using data from short-term (6 and 12 months) double-blind RCTs comparing as-needed nalmefene treatment to placebo, and mortality risks from meta-analyses on all-cause-mortality risk by reduction of drinking in people with alcohol dependence. A reduction in drinking in the RCTs was defined by shifts in drinking risk levels established by the European Medicines Agency. Results showed that the reduction of drinking in the nalmefene group was associated with a reduction in mortality risk by 8% (95% CI: 2%, 13%) when compared to the placebo group. Sensitivity analyses confirmed a significant effect. Thus comparing the difference between nalmefene and placebo in reduction in drinking levels with results on all-cause mortality risk from meta-analyses indicated a clinically relevant reduction in mortality risk. Given the high mortality risk of people with alcohol dependence, abstinence or a reduction in drinking have been shown to reduce mortality risk and should be considered treatment goals. [ABSTRACT FROM AUTHOR]

Objective To refine estimates of the burden of alcohol-related oesophageal cancer in Japan. Methods We searched PubMed for published reviews and original studies on alcohol intake, aldehyde dehydrogenase polymorphisms, and risk for oesophageal cancer in Japan, published before 2014. We conducted random-effects meta-analyses, including subgroup analyses by aldehyde dehydrogenase variants. We estimated deaths and loss of disability-adjusted life years (DALYs) from oesophageal cancer using exposure distributions for alcohol based on age, sex and relative risks per unit of exposure. Findings We identified 14 relevant studies. Three cohort studies and four case-control studies had dose–response data. Evidence from cohort studies showed that people who consumed the equivalent of 100 g/day of pure alcohol had an 11.71 fold, (95% confidence interval, CI: 2.67-51.32) risk of oesophageal cancer compared to those who never consumed alcohol. Evidence from case-control studies showed that the increase in risk was 33.11 fold (95% CI: 8.15-134.43) in the population at large. The difference by study design is explained by the 159 fold (95% CI: 27.2-938.2) risk among those with an inactive aldehyde dehydrogenase enzyme variant. Applying these dose–response estimates to the national profile of alcohol intake yielded 5279 oesophageal cancer deaths and 102 988 DALYs lost - almost double the estimates produced by the most recent global burden of disease exercise. Conclusion Use of global dose–response data results in an underestimate of the burden of disease from oesophageal cancer in Japan. Where possible, national burden of disease studies should use results from the population concerned. [ABSTRACT FROM AUTHOR]

Introduction and Aims The present analysis contributes to understanding the societal distribution of alcohol-attributable harm by investigating socioeconomic inequality and related gender differences in alcohol-attributable mortality. Design and Methods A systematic literature search was performed on Web of Science, MEDLINE, PsycINFO and ETOH from their inception until February 2013. Articles were included when they reported data on alcohol-attributable mortality by socioeconomic status ( SES), operationalised as education, occupation, employment status or income. Gender-specific relative risks ( RR) comparing low with high SES were pooled using random effects meta-analyses. Gender differences were additionally investigated in random effects meta-regressions. Results Nineteen articles from 14 countries were included. For women, significant RRs across all measures of SES, except employment status, were found, ranging between 1.75 [95% confidence interval ( CI) 1.21-2.54; occupation] and 4.78 (95% CI 2.57-8.87; income). For men, all measures of SES showed significant RRs ranging between 2.88 (95% CI 2.45-3.40; income) and 12.25 (95% CI 11.45-13.10; employment status). While RRs for men were in general slightly higher, only for occupation this gender difference was above chance ( P = 0.01). Results refer to deaths 100% attributable to alcohol. Discussion and Conclusions The results are predominantly based on data from high-income countries, limiting generalisability. Alcohol-attributable mortality is strongly distributed to the disadvantage of persons with a low SES. Marked gender differences in this inequality were found for occupation. Possibly male-dominated occupations of low SES were more strongly related to risky drinking cultures compared with female-dominated occupations of the same SES. [ABSTRACT FROM AUTHOR]

Background: Alcohol consumption is a major global risk factor for mortality and morbidity. Much discussion has revolved around the diverse findings on the complex relationship between alcohol consumption and the leading cause of death and disability, ischemic heart disease (IHD). Methods: We conducted a systematic search of the literature up to August 2014 using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify meta-analyses and observational studies examining the relationship between alcohol drinking, drinking patterns, and IHD risk, in comparison to lifetime abstainers. In a narrative review we have summarized the many meta-analyses published in the last 10 years, discussing the role of confounding and experimental evidence. We also conducted meta-analyses examining episodic heavy drinking among on average moderate drinkers. Results: The narrative review showed that the use of current abstainers as the reference group leads to systematic bias. With regard to average alcohol consumption in relation to lifetime abstainers, the relationship is clearly J-shaped, supported by short-term experimental evidence and similar associations within strata of potential confounders, except among smokers. Women experience slightly stronger beneficial associations and also a quicker upturn to a detrimental effect at lower levels of average alcohol consumption compared to men. There was no evidence that chronic or episodic heavy drinking confers a beneficial effect on IHD risk. People with alcohol use disorder have an elevated risk of IHD (1.5- to 2-fold). Results from our quantitative meta-analysis showed that drinkers with average intake of <30 g/day and no episodic heavy drinking had the lowest IHD risk (relative risk = 0.64, 95% confidence interval 0.53 to 0.71). Drinkers with episodic heavy drinking occasions had a risk similar to lifetime abstainers (relative risk = 1.12, 95% confidence interval 0.91 to 1.37). Conclusions: Epidemiological evidence for a beneficial effect of low alcohol consumption without heavy drinking episodes is strong, corroborated by experimental evidence. However, episodic and chronic heavy drinking do not provide any beneficial effect on IHD. Thus, average alcohol consumption is not sufficient to describe the risk relation between alcohol consumption and IHD. Alcohol policy should try to reduce heavy drinking patterns. [ABSTRACT FROM AUTHOR]

Background: Factors underlying socioeconomic inequalities in mortality are not well understood. This study contributes to our understanding of potential pathways to result in socioeconomic inequalities, by examining alcohol consumption as one potential explanation via comparing socioeconomic inequalities in alcohol-attributable mortality and all-cause mortality.Methods: Web of Science, MEDLINE, PsycINFO and ETOH were searched systematically from their inception to second week of February 2013 for articles reporting alcohol-attributable mortality by socioeconomic status, operationalized by using information on education, occupation, employment status or income. The sex-specific ratios of relative risks (RRRs) of alcohol-attributable mortality to all-cause mortality were pooled for different operationalizations of socioeconomic status using inverse-variance weighted random effects models. These RRRs were then combined to a single estimate.Results: We identified 15 unique papers suitable for a meta-analysis; capturing about 133 million people, 3 741 334 deaths from all causes and 167 652 alcohol-attributable deaths. The overall RRRs amounted to RRR = 1.78 (95% confidence interval (CI) 1.43 to 2.22) and RRR = 1.66 (95% CI 1.20 to 2.31), for women and men, respectively. In other words: lower socioeconomic status leads to 1.5-2-fold higher mortality for alcohol-attributable causes compared with all causes.Conclusions: Alcohol was identified as a factor underlying higher mortality risks in more disadvantaged populations. All alcohol-attributable mortality is in principle avoidable, and future alcohol policies must take into consideration any differential effect on socioeconomic groups. [ABSTRACT FROM AUTHOR]

Background: Alcohol use disorders (AUD) are highly disabling. Recent studies reported much higher relative risks for all-cause mortality in AUD patients compared with earlier studies. Systematic evidence regarding cause-specific mortality among AUD patients has been unavailable to date.Methods: Studies were identified through MEDLINE, EMBASE and Web of Science up to August 2012. Following MOOSE guidelines, prospective and historical cohort studies assessing cause-specific mortality risk from AUD patients at baseline compared with the general population were selected. Data on several study characteristics, including AUD assessment, follow-up period, setting, location and cause-specific mortality risk compared with the general population were abstracted. Random-effect meta-analyses were conducted.Results: Overall, 17 observational studies with 6420 observed deaths among 28 087 AUD patients were included. Pooled standardized mortality ratios (SMRs) after 10 years of follow-up among men were 14.8 (95% confidence interval: 8.7–24.9) for liver cirrhosis, 18.0 (11.2–30.3) for mental disorders, 6.6 (5.0–8.8) for death by injury and around 2 for cancer and cardiovascular diseases. SMRs were substantially higher in women, with fewer studies available. For many outcomes the risk has been increasing substantially over time.Conclusions: Cause-specific mortality among AUD patients was high in all major categories compared with the general population. There has been a lack of recent research, and future studies should focus on the influence of comorbidities on excess mortality risk among AUD patients. Efforts to reduce these risks should be a priority, given that successful treatment reduces mortality risk substantially for a relatively common psychiatric disease. [ABSTRACT FROM PUBLISHER]

Aims To conduct a systematic review and meta-analysis on all-cause mortality in people with alcohol use disorders. Methods Using the Meta-analysis Of Observational Studies in Epidemiology ( MOOSE) guidelines, studies were identified through MEDLINE, EMBASE, and Web of Science up to August, 2012. Prospective and historical cohort studies including a comparison of alcohol use disorder with a control group investigating all-cause mortality risk were included. Results This meta-analysis included 81 observational studies with 221 683 observed deaths among 853 722 people with alcohol use disorder. In men, the relative risk ( RR) among clinical samples was 3.38 (95% confidence interval [ CI]: 2.98-3.84); in women it was 4.57 (95% CI: 3.86-5.42). Alcohol use disorders identified in general population surveys showed a twofold higher risk compared with no alcohol use disorder in men; no data were available for women. RRs were markedly higher for those ≤40 years old (ninefold in men, 13-fold in women) while still being at least twofold among those aged 60 years or older. Conclusions Mortality in people with alcohol use disorders is markedly higher than thought previously. Women have generally higher mortality risks than men. Among all people with alcohol use disorders, people in younger age groups and people in treatment show substantially higher mortality risk than others in that group. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims Most, but not all, epidemiological studies suggest a cardioprotective association for low to moderate average alcohol consumption. The objective was to quantify the dose-response relationship between average alcohol consumption and ischaemic heart disease (IHD) stratified by sex and IHD end-point (mortality versus morbidity). Methods A systematic search of published studies using electronic databases (1980-2010) identified 44 observational studies (case-control or cohort) reporting a relative risk measure for average alcohol intake in relation to IHD risk. Generalized least-squares trend models were used to derive the best-fitting dose-response curves in stratified continuous meta-analyses. Categorical meta-analyses were used to verify uncertainty for low to moderate levels of consumption in comparison to long-term abstainers. Results The analyses used 38 627 IHD events (mortality or morbidity) among 957 684 participants. Differential risk curves were found by sex and end-point. Although some form of a cardioprotective association was confirmed in all strata, substantial heterogeneity across studies remained unexplained and confidence intervals were relatively wide, in particular for average consumption of one to two drinks/day. Conclusions A cardioprotective association between alcohol use and ischaemic heart disease cannot be assumed for all drinkers, even at low levels of intake. More evidence on the overall benefit-risk ratio of average alcohol consumption in relation to ischaemic heart disease and other diseases is needed in order to inform the general public or physicians about safe or low-risk drinking levels. [ABSTRACT FROM AUTHOR]

Background: The relationship between alcohol consumption and ischaemic heart disease (IHD) risk is complex and several issues remain unresolved because many studies used rather crude exposure measures often based on one or two questions. The objective of this study was to investigate the association between heavy drinking occasions and IHD mortality while controlling for average daily alcohol intake and separating former drinkers from lifetime abstainers.Methods: Cox regression analyses were used with IHD mortality as the outcome in a sample of 9934 participants of the US National Alcohol Surveys conducted in 1984 and 1995.Results: To the end of 2006, 326 deaths from IHD were recorded in the 11- to 22-year follow-up period. Any past heavy drinking occasions in former drinkers [hazard ratio (HR) = 2.06; 95% confidence interval (95% CI): 1.10-3.85] compared with former drinkers without such drinking occasions, and any heavy drinking occasion in current drinkers at baseline (HR = 2.05; 95% CI: 1.03-3.98) compared with current drinkers with average daily intake of one to two drinks, were associated with higher IHD mortality in men and any heavy drinking occasions among drinkers of up to 1 drink average consumption in women with similar effect size. Confounding effects from age, race, education, employment, income, marital status, geographical region, depression score, survey period or other drug use were small.Conclusions: Among former and current drinkers, heavy drinking occasions should be taken into account when examining the complex association of alcohol consumption on IHD mortality risk. [ABSTRACT FROM AUTHOR]

Current abstainers from alcohol have been identified as an inadequate reference group in epidemiologic studies of the effects of alcohol, because inclusion of former drinkers might lead to overestimation of the protective effects and underestimation of the detrimental effects of drinking alcohol. The authors’ objective in the current study was to quantify this association for ischemic heart disease (IHD). Electronic databases were systematically searched for relevant case-control or cohort studies published from 1980 to 2010. Thirty-eight articles fulfilled the inclusion criteria, contributing a total of 5,613 IHD events and 12,097 controls among case-control studies and 1,387 events with combined endpoints and 7,183 events stratified by endpoint among 232,621 persons at risk among cohort studies. Pooled estimates for the subset stratified by sex and endpoint showed a significantly increased risk among former drinkers compared with long-term abstainers for IHD mortality ( among men; relative risk = 1.25, 95% confidence interval: 1.15, 1.36; among women relative risk = 1.54, 95% confidence interval: 1.17, 2.03). For IHD morbidity, the estimates for both sexes were close to unity and not statistically significant. Results were robust in several sensitivity analyses. In future studies, researchers should separate former drinkers from the reference category to obtain unbiased effect estimates. Implications for the overall beneficial and detrimental effects of alcohol consumption on IHD are discussed below. [ABSTRACT FROM PUBLISHER]

Contrary to a cardioprotective effect of moderate regular alcohol consumption, accumulating evidence points to a detrimental effect of irregular heavy drinking occasions (>60 g of pure alcohol or ≥5 drinks per occasion at least monthly) on ischemic heart disease risk, even for drinkers whose average consumption is moderate. The authors systematically searched electronic databases from 1980 to 2009 for case-control or cohort studies examining the association of irregular heavy drinking occasions with ischemic heart disease risk. Studies were included if they reported either a relative risk estimate for intoxication or frequency of ≥5 drinks stratified by or adjusted for total average alcohol consumption. The search identified 14 studies (including 31 risk estimates) containing 4,718 ischemic heart disease events (morbidity and mortality). Using a standardized protocol, the authors extracted relative risk estimates and their variance, in addition to study characteristics. In a random-effects model, the pooled relative risk of irregular heavy drinking occasions compared with regular moderate drinking was 1.45 (95% confidence interval: 1.24, 1.70), with significant between-study heterogeneity (I2 = 53.9%). Results were robust in several sensitivity analyses. The authors concluded that the cardioprotective effect of moderate alcohol consumption disappears when, on average, light to moderate drinking is mixed with irregular heavy drinking occasions. [ABSTRACT FROM PUBLISHER]

In this article the authors reflect on Mendelian research studies which have suggested that there is not a link between moderate alcohol use and the prevention of coronary heart disease. They suggest that the studies make assumptions which may not be warranted. They argue that additional research on the relationship between moderate alcohol consumption and the prevention of coronary heart disease needs to be conducted to verify the results of the Mendelian studies.

The authors discuss the need for newer data regarding the use of cannabis by youth. They mention the increased levels of tetrahydrocannabinol and its impact, the greater risk factors for mental illness, and the increased use of marijuana with its legalization as contributing to this need.

A letter to the editor is presented in response to the article "A reply to Roerecke & Rehm: continuing questions about alcohol and health benefits" by T. Stockwell in the 2013 issue of "Addiction."

The article presents the author's comments on the impact of alcohol on the cardiovascular system. According to the authors, the cardioprotective effect of alcohol has been established in medical epidemiology, but problems are associated with most of the studies. The authors say that various cardiovascular conditions such as ischaemic heart disease and ischaemic stroke are harmfully impacted by alcohol, including haemorrhagic stroke, hypertensive diseases, and atrial fibrillation.

Background: Depressive disorders (DD) and alcohol use disorders (AUD) frequently co-occur. They are key to understanding the current increases in "deaths of despair" among individuals with lower socioeconomic status (SES). The aim of this study was to assess the prospective bidirectional associations between AUD and DD, as well as the effect of SES on these two conditions.Methods: The National Epidemiologic Survey on Alcohol and Related Conditions is a cohort study representative of the US adult population, which began in 2001-2002, with follow-up interviews conducted 3 years later. SES was primarily operationalized as educational attainment. AUD, DD, and their levels of severity were defined according to the DSM-5 criteria.Results: The risk of developing an incident DD increased gradually with the recency and the severity of AUD at baseline, but the converse was not observed. Lower SES was an independent risk for incident AUD or DD. SES did not modify the prospective association between AUD and DD.Limitations: The absence of interaction between SES and moderate or severe AUD for the incident DD must be considered with caution due to the limited number of DD cases reported in these AUD categories.Conclusions: This result is consistent with a causal relationship between AUD and DD, and suggests that therapeutic interventions for AUD may also have beneficial effects to lower DD rates. The independent effects of a lower SES and AUD on DD may result in a vulnerable population cumulating disorders with heavy consequences on health and social well-being. [ABSTRACT FROM AUTHOR]

Commentary to: Selection biases in observational studies affect associations between ‘moderate’ alcohol consumption and mortality [ABSTRACT FROM AUTHOR]

Purpose: The prevalence of postoperative emergence delirium in paediatric patients (pedED) following desflurane anaesthesia is considerably high at 50–80%. Although several pharmacological prophylactic strategies have been introduced to reduce the risk of pedED, conclusive evidence about the superiority of these individual regimens is lacking. The aim of the current study was to assess the potential prophylactic effect and safety of individual pharmacotherapies in the prevention of pedED following desflurane anaesthesia. Methods: This frequentist model network meta-analysis (NMA) of randomized controlled trials (RCTs) included peer-reviewed RCTs of either placebo-controlled or active-controlled design in paediatric patients under desflurane anaesthesia. Results: Seven studies comprising 573 participants were included. Overall, the ketamine + propofol administration [odds ratio (OR) = 0.05, 95% confidence intervals (95%CIs) 0.01–0.33], dexmedetomidine alone (OR = 0.13, 95%CIs 0.05–0.31), and propofol administration (OR = 0.30, 95%CIs 0.10–0.91) were associated with a significantly lower incidence of pedED than the placebo/control groups. In addition, only gabapentin and dexmedetomidine were associated with a significantly higher improvement in the severity of emergence delirium than the placebo/control groups. Finally, the ketamine + propofol administration was associated with the lowest incidence of pedED, whereas gabapentin was associated with the lowest severity of pedED among all of the pharmacologic interventions studied. Conclusions: The current NMA showed that ketamine + propofol administration was associated with the lowest incidence of pedED among all of the pharmacologic interventions studied. Future large-scale trials to more fully elucidate the comparative benefits of different combination regimens are warranted. Trial registration: PROSPERO CRD42021285200. [ABSTRACT FROM AUTHOR]

The author discusses the effect of alcohol consumption on all-cause mortality and implications for burden-of-disease studies and for low risk-drinking guidelines. Topics discussed include adverse and protective effects of alcohol on body, protective impact of light drinking, and determination of true comparisons to abstention in Western high-income countries.

A response by Michael Roerecke and Jürgen Rehm to a commentary "Commentary on Roerecke & Rehm (2012): The state of the science on moderate drinking and health – a case of heterogeneity in and heterogeneity out?" by T. Stockwell in the 2012 issue of Addiction is presented.

Background: Although alcohol consumption has long been considered as a risk factor for chronic disease, the relationship to cardiovascular disease (CVD) is complex and involves at least two dimensions: average volume of alcohol consumption and patterns of drinking. The objective of this contribution was to estimate the burden of CVD mortality caused by alcohol consumption.Methods: Risk assessment modelling with alcohol-attributable CVD mortality as primary outcome. The mortality burden of ischaemic heart disease (IHD) and ischaemic stroke (IS) attributable to alcohol consumption was estimated using attributable-fraction methodology. Relative Risk (RR) data for IHD and IS were obtained from the most comprehensive meta-analyses (except for Russia and surrounding countries where alcohol RR data were obtained from a large cohort study). Age-group specific RRs were calculated, based on large studies. Data on mortality were obtained from the World Health Organization's Global Health Estimates and alcohol consumption data were obtained from the Global Information System on Alcohol and Health. Risk of former drinkers was modelled taking into account global differences in the prevalence of sick quitters among former drinkers. Alcohol-attributable mortality estimates for all other CVD causes except IHD and IS were obtained from the 2014 Global Status Report on Alcohol and Health.Results: An estimated 780,381 CVD deaths (441,893 and 338,490 CVD deaths among men and women respectively) were attributable to alcohol consumption globally in 2012, accounting for 1.4 % of all deaths and 26.6 % of all alcohol-attributable deaths. This is in contrast to the previously estimated 1,128,273 CVD deaths attributable to alcohol consumption globally, and represents a decrease of 30.8 % in alcohol-attributable CVD mortality and of 10.6 % in the global burden of all alcohol-attributable deaths.Conclusions: When the most comprehensive and recent systematic reviews and meta-analyses are taken as bases, the net impact of alcohol consumption on CVD is lower than previously estimated. [ABSTRACT FROM AUTHOR]

Background and Aims Cannabis use is associated with several adverse health effects. However, little is known about the cannabis-attributable burden of disease. This study quantified the age-, sex- and adverse health effect-specific cannabis attributable (1)mortality, (2) years of life lost due to premature mortality (YLLs), (3) years of life lost due to disability (YLDs) and (4) disability-adjusted life years (DALYs) in Canada in 2012. Design Epidemiological modeling. Setting Canada. Participants Canadians aged ≥ 15 years in 2012. Measurements Using comparative risk assessment methodology, cannabis-attributable fractions were computed using Canadian exposure data and risk relations from large studies or meta-analyses. Outcome data were obtained from Canadian databases and the World Health Organization. The 95% confidence intervals (CIs)were computed using Monte Carlo methodology. Findings Cannabis use was estimated to have caused 287 deaths (95% CI = 108, 609), 10 533 YLLs (95% CI = 4760, 20 833), 55 813 YLDs (95% CI = 38 175, 74 094) and 66 346 DALYs (95% CI = 47 785, 87 207), based on causal impacts on cannabis use disorders, schizophrenia, lung cancer and road traffic injuries. Cannabis-attributable burden of disease was highest among young people, and males accounted for twice the burden than females. Cannabis use disorders were the most important single cause of the cannabis-attributable burden of disease. Conclusions The cannabis-attributable burden of disease in Canada in 2012 included 55 813 years of life lost due to disability, caused mainly by cannabis use disorders. Although the cannabis attributable burden of disease was substantial, it was much lower compared with other commonly used legal and illegal substances. Moreover, the evidence base for cannabis-attributable harms was smaller. [ABSTRACT FROM AUTHOR]

Non-medical prescription opioid use (NMPOU) constitutes a substantial clinical and public health concern in North America. Although there is evidence of elevated rates of mental health problems among people with NMPOU, the extent of these correlations specifically in treatment samples has not been systematically assessed. A systematic review and meta-analysis were conducted for Axis-1 psychiatric diagnoses and symptoms with a principal focus on depression and anxiety disorders in substance use treatment samples reporting NMPOU at admission to treatment (both criteria within past 30 days). 11 unique studies (all from either the United States or Canada) met inclusion criteria and were included in the meta-analysis. The pooled prevalence of ‘any’ mental health problems (both diagnosis and symptoms) among substance abuse treatment patients reporting NMPOU was 43% (95% CI: 32%–54%; I2 for inter-study heterogeneity: 99.5%). The pooled prevalence of depression diagnosis among substance abuse treatment patients reporting NMPOU was 27% (95% CI: 9%–45%; I2: 99.2%); the pooled prevalence of anxiety diagnosis in the sample was 29% (95% CI: 14%–44%; I2: 98.7%). The prevalence rates of psychiatric problems (both diagnosis and symptoms), depression diagnosis and anxiety diagnosis are disproportionately high in substance use treatment samples reporting NMPOU relative to general population rates. Adequate and effective clinical strategies are needed to address co-occurring NMPOU and mental health in substance use treatment systems, especially given rising treatment demand for NMPOU. Efforts are needed to better understand the temporal and causal relationships among NMPOU, mental health problems, and treatment seeking in order to improve interventions. [Copyright &y& Elsevier]

To determine whether sub-clinical levels of drinking may contribute to suicide risk, and whether the risk differs by sex, we aimed to evaluate the relationship between average amount of alcohol consumed per day and death by suicide. A systematic literature search was performed in Embase, Medline, PsycINFO, PubMed, and Web of Science from database inception up to April 27, 2022. The search strategies incorporated a combination of medical subject headings and keywords for "alcohol use" and "suicide". One-stage dose-response meta-analyses using a restricted maximum likelihood random-effect estimator were conducted to explore the relationship between average alcohol volume consumed and suicide, by sex. Three different shapes of the dose-response relationship–linear (on the log-scale), quadratic, and restrictive cubic splines–were tested. A total of eight studies were included (three studies for females (n=781,205), and eight studies for males (n=1,215,772)). A linear dose-response relationship between average alcohol volume consumed and the log-risk of suicide was identified for both males and females. For males and females, a relative risk (RR) of 1.11 (95% CI: 1.05, 1.18) and 1.64 (95% CI: 1.07, 2.51) for suicide when consuming an average of 10 g of pure alcohol per day compared to lifetime abstention, 1.38 (95% CI: 1.14, 1.66) and 4.39 (95% CI: 1.21, 15.88) for 30 g/day, and 1.71 (95% CI: 1.25, 2.33) and 11.75 (95% CI: 1.38, 100.33) for 50 g/day, respectively. As consumption increases, the risk of suicide increases proportionally. The risk of suicide associated with average daily alcohol consumption may be elevated for females, compared with males. Albeit, more research is needed, particularly among females. • This is the first evidence synthesis on the dose-response relationship between average alcohol consumption and death by suicide. • Average alcohol consumption appears to have a linear dose-response relationship with the log-risk of suicide for both sexes. • The risk of suicide associated with average daily alcohol consumption may be elevated for females, compared with males. [ABSTRACT FROM AUTHOR]

Introduction: There is evidence to suggest that tobacco use is associated with suicide attempts. However, it is unclear whether such an association can be extended to include secondhand smoke exposure. Using nationally representative data of school-attending adolescents from 33 countries, we examined the association of tobacco use and exposure to secondhand smoke with suicide attempts.Methods: We used data from the Global School-based Student Health Survey, a cross-sectional survey conducted among adolescents 12-15 years of age. We used logistic regression to estimate the country-specific associations. We then conducted random effect meta-analyses to obtain overall and country-income level pooled estimates. Lastly, we used logistic regression analyses to investigate a dose-response association of cigarette smoking and exposure to secondhand smoke with suicide attempts.Results: A positive association between tobacco use and suicide attempts among adolescents was present regardless of country-income level (low income: odds ratio 4.98, 95% CI: 3.11-7.96; lower middle income: 3.47, 2.91-4.15; upper middle income: 3.09, 2.75-3.47; and high income: 3.18, 2.63-3.84) and gender (boys: 3.28, 2.86-3.76; girls: 3.86, 3.30-4.51). Exposure to secondhand smoke was associated with suicide attempts, albeit weakly, among girls only (1.26, 1.14-1.39; boys: 1.00, 0.87-1.15). There was some evidence that a dose-response association of cigarette smoking and exposure to secondhand smoke with suicide attempts may only exist among girls.Conclusions: Adolescents who use tobacco, and adolescent girls exposed to secondhand smoke were found to be more likely to attempt suicide; however, future longitudinal studies are warranted to assess causality.Implications: Our findings indicate that routine screening of adolescents for tobacco use should be implemented globally, especially when assessing suicidal behaviors and risk. Future longitudinal and intervention studies are warranted to assess causality and whether prevention efforts such as tobacco control interventions and programmes targeting tobacco use and exposure to secondhand smoke among adolescents could ultimately lead to a reduction in the occurrence of suicide attempts. [ABSTRACT FROM AUTHOR]

• Less than weekly cannabis use during youth was significantly associated with health service use for mood and anxiety disorders (MADs). • Weekly or more cannabis use was not significantly associated with MAD health service use. • Interaction analyses suggested no effect modification by sex or age (additive or multiplicative). Epidemiologic research suggests a modest association between youth cannabis use and mood and anxiety disorders (MADs). However, current evidence is based mostly on cohort studies using data from the 20th century when cannabis was significantly less potent than today. We linked population-based survey data from 2009 to 2012 with administrative records of health services covered under universal healthcare up to 2017. The cohort included youth aged 12 to 24 years at baseline living in Ontario, Canada with no prior MAD health service use (n = 8,252). We conducted a multivariable Cox model to estimate the association between cannabis use frequency (never,

A letter to the editor is presented in response to a commentary by Wayne Hall on the authors' article "The Burden of Disease Attributable to Cannabis--Implications for Policy" in volume 111 of the periodical.

Objective. To estimate the prevalence of alcohol consumption during pregnancy among the general population of Latin America and the Caribbean, by country, in 2012. Methods. Three steps were taken: a comprehensive, systematic literature search; meta- analyses, assuming a random-effects model for countries with published studies; and regression modelling (data prediction) for countries with either no published studies or too few to obtain an estimate. Results. Based on 24 existing studies, the pooled prevalence of alcohol consumption during pregnancy among the general population was estimated for Brazil (15.2%; 95% confidence interval [95%CI]: 10.4%-20.8%) and Mexico (1.2%; 95%CI: 0.0%-2.7%). The prevalence of alcohol consumption during pregnancy among the general population was predicted for 31 countries and ranged from 4.8% (95%CI: 4.2%-5.4%) in Cuba to 23.3% (95%CI: 20.1%-26.5%) in Grenada. Conclusions. Greater prevention efforts and measures are needed in the countries of Latin America and the Caribbean to prevent pregnant women from consuming alcohol during pregnancy and decrease the rates of Fetal Alcohol Spectrum Disorder. Additional high quality studies on the prevalence of alcohol consumption during pregnancy in Latin America and the Caribbean are also needed. [ABSTRACT FROM AUTHOR]

Background and aims Alcohol use is a major contributor to injuries, mortality and the burden of disease. This review updates knowledge on risk relations between dimensions of alcohol use and health outcomes to be used in global and national Comparative Risk Assessments (CRAs). Methods Systematic review of reviews and meta-analyses on alcohol consumption and health outcomes attributable to alcohol use. For dimensions of exposure: volume of alcohol use, blood alcohol concentration and patterns of drinking, in particular heavy drinking occasions were studied. For liver cirrhosis, quality of alcohol was additionally considered. For all outcomes (mortality and/or morbidity): cause of death and disease/injury categories based on International Classification of Diseases (ICD) codes used in global CRAs; harm to others. Results In total, 255 reviews and meta-analyses were identified. Alcohol use was found to be linked causally to many disease and injury categories, with more than 40 ICD-10 three-digit categories being fully attributable to alcohol. Most partially attributable disease categories showed monotonic relationships with volume of alcohol use: the more alcohol consumed, the higher the risk of disease or death. Exceptions were ischaemic diseases and diabetes, with curvilinear relationships, and with beneficial effects of light to moderate drinking in people without heavy irregular drinking occasions. Biological pathways suggest an impact of heavy drinking occasions on additional diseases; however, the lack of medical epidemiological studies measuring this dimension of alcohol use precluded an in-depth analysis. For injuries, except suicide, blood alcohol concentration was the most important dimension of alcohol use. Alcohol use caused marked harm to others, which has not yet been researched sufficiently. Conclusions Research since 2010 confirms the importance of alcohol use as a risk factor for disease and injuries; for some health outcomes, more than one dimension of use needs to be considered. Epidemiological studies should include measurement of heavy drinking occasions in line with biological knowledge. [ABSTRACT FROM AUTHOR]

Background and Aims Unrecorded alcohol constitutes about 30% of all alcohol consumed globally. The aims of this systematic review were to determine the epidemiology (occurrence, types, prevalence) of unrecorded alcohol consumption in different countries/regions, analyse the chemical composition of unrecorded alcohol and examine health outcomes caused by the consumption of unrecorded alcohol, based on either epidemiology or toxicology. Methods A systematic search for, and qualitative analysis of, papers with empirical results on the different categories of unrecorded alcohol, based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses ( PRISMA) guidelines. Results Unrecorded alcohol was widespread in all regions of the world. Artisanal fermented beverages and spirits were the most common categories of unrecorded alcohol globally, and were available on all continents. In India, industrially produced spirits (country spirits) were most prevalent. In Russia and countries of the former Soviet Union, surrogate alcohols complemented artisanal spirits. Cross-border shopping was the most prevalent method of obtaining unrecorded alcohol in parts of Europe. Ethanol was the most harmful ingredient of unrecorded alcohol, and health consequences due to other ingredients found in unrecorded alcohol were scarce. However, as unrecorded alcohol is usually the least expensive form of alcohol available in many countries, it may contribute to higher rates of chronic and irregular heavy drinking. Conclusions Very large amounts of alcohol are produced globally that go unrecorded. The primary harm from this kind of alcohol arises from the fact that it is typically much cheaper than licit alcohol. [ABSTRACT FROM AUTHOR]

Background Alcohol use disorders ( AUD) have long been considered to be some of the most disabling mental disorders; however, empirical data on the burden of disease associated with AUD have been sparse. The objective of this article is to quantify the burden of disease (in disability-adjusted life years [ DALYs] lost), deaths, years of life lost due to premature mortality ( YLL), and years of life lost due to disability ( YLD) associated with AUD for the United States in 2005. Methods Statistical modeling was based on epidemiological indicators derived from the National Epidemiologic Survey on Alcohol and Related Conditions. Formal consistency analyses were applied. Risk relations were taken from recent meta-analyses and the disability weights from the burden of disease study of the National Institutes of Health. Monte Carlo simulations were used to derive confidence intervals. All analyses were performed by sex and age. Sensitivity analyses were undertaken on key indicators. Results In the United States in 2005, 65,000 deaths, 1,152,000 YLL, 2,443,000 YLD, and 3,595,000 DALYs were associated with AUD. For individuals 18 years of age and older, AUD were associated with 3% of all deaths (5% for men and 1% for women), and 5% of all YLL (7% for men and 2% for women). The majority of the burden of disease associated with AUD stemmed from YLD, which accounted for 68% of DALYs associated with AUD (66% for men and 74% for women). The youngest age group had the largest proportion of DALYs associated with AUD stemming from YLD. Conclusions Using data from a large representative survey (checked for consistency) and by combining these data with the best available evidence, we found that AUD were associated with a larger burden of disease than previously estimated. To reduce this disease burden, implementation of prevention interventions and expansion of treatment are necessary. [ABSTRACT FROM AUTHOR]

Introduction and Aims. Alcohol is an established risk factor for liver cirrhosis. It remains unclear, however, whether this relationship follows a continuous dose-response pattern or has a threshold. Also, the influences of sex and end-point (i.e. mortality vs. morbidity) on the association are not known. To address these questions and to provide a quantitative assessment of the association between alcohol intake and risk of liver cirrhosis, we conducted a systematic review and meta-analysis of cohort and case-control studies. Design and Methods. Studies were identified by a literature search of Ovid MEDLINE, EMBASE, Web of Science, CINAHL, PsychINFO, ETOH and Google Scholar from January 1980 to January 2008 and by searching the references of retrieved articles. Studies were included if quantifiable information on risk and related confidence intervals with respect to at least three different levels of average alcohol intake were reported. Both categorical and continuous meta-analytic techniques were used to model the dose-response relationship. Results. Seventeen studies met the inclusion criteria. We found some indications for threshold effects. Alcohol consumption had a significantly larger impact on mortality of liver cirrhosis compared with morbidity. Also, the same amount of average consumption was related to a higher risk of liver cirrhosis in women than in men. Discussion and Conclusions. Overall, end-point was an important source of heterogeneity among study results. This result has important implications not only for studies in which the burden of disease attributable to alcohol consumption is estimated, but also for prevention. [Rehm J, Taylor B, Mohapatra S, Irving H, Baliunas D, Patra J, Roerecke M. Alcohol as a risk factor for liver cirrhosis: A systematic review and meta-analysis. Drug Alcohol Rev 2010] [ABSTRACT FROM AUTHOR]

Aims As part of a larger study to estimate the global burden of disease and injury attributable to alcohol: to evaluate the evidence for a causal impact of average volume of alcohol consumption and pattern of drinking on diseases and injuries; to quantify relationships identified as causal based on published meta-analyses; to separate the impact on mortality versus morbidity where possible; and to assess the impact of the quality of alcohol on burden of disease. Methods Systematic literature reviews were used to identify alcohol-related diseases, birth complications and injuries using standard epidemiological criteria to determine causality. The extent of the risk relations was taken from meta-analyses. Results Evidence of a causal impact of average volume of alcohol consumption was found for the following major diseases: tuberculosis, mouth, nasopharynx, other pharynx and oropharynx cancer, oesophageal cancer, colon and rectum cancer, liver cancer, female breast cancer, diabetes mellitus, alcohol use disorders, unipolar depressive disorders, epilepsy, hypertensive heart disease, ischaemic heart disease (IHD), ischaemic and haemorrhagic stroke, conduction disorders and other dysrhythmias, lower respiratory infections (pneumonia), cirrhosis of the liver, preterm birth complications and fetal alcohol syndrome. Dose–response relationships could be quantified for all disease categories except for depressive disorders, with the relative risk increasing with increased level of alcohol consumption for most diseases. Both average volume and drinking pattern were linked causally to IHD, fetal alcohol syndrome and unintentional and intentional injuries. For IHD, ischaemic stroke and diabetes mellitus beneficial effects were observed for patterns of light to moderate drinking without heavy drinking occasions (as defined by 60+ g pure alcohol per day). For several disease and injury categories, the effects were stronger on mortality compared to morbidity. There was insufficient evidence to establish whether quality of alcohol had a major impact on disease burden. Conclusions Overall, these findings indicate that alcohol impacts many disease outcomes causally, both chronic and acute, and injuries. In addition, a pattern of heavy episodic drinking increases risk for some disease and all injury outcomes. Future studies need to address a number of methodological issues, especially the differential role of average volume versus drinking pattern, in order to obtain more accurate risk estimates and to understand more clearly the nature of alcohol–disease relationships. [ABSTRACT FROM AUTHOR]

Justice policy is typically based more on political considerations than on research results. One way to break down barriers between researchers and policy-makers is to encourage partnerships. AUTO21, a member of the Networks of Centres of Excellence program, is designed to facilitate partnerships. The Antisocial Behaviour and the Automobile project focuses on auto theft, driving under the influence of alcohol and cannabis, and road rage/driver aggression. The research areas that have had the greatest policy impact benefited from strong partnerships with organizations that have the visibility, authority, and resources to implement significant changes in program funding and social policy. These areas also have an extensive body of prior research. [ABSTRACT FROM AUTHOR]

Background: Observational studies have suggested a complex relationship between alcohol consumption and stroke, dependent on sex, type of stroke and outcome (morbidity vs. mortality). We undertook a systematic review and a meta-analysis of studies assessing the association between levels of average alcohol consumption and relative risks of ischemic and hemorrhagic strokes separately by sex and outcome. This meta-analysis is the first to explicitly separate morbidity and mortality of alcohol-attributable stroke and thus has implications for public health and prevention. Methods: Using Medical Subject Headings (alcohol drinking, ethanol, cerebrovascular accident, cerebrovascular disorders, and intracranial embolism and thrombosis and the key word stroke), a literature search of MEDLINE, EMBASE, CINAHL, CABS, WHOlist, SIGLE, ETOH, and Web of Science databases between 1980 to June 2009 was performed followed by manual searches of bibliographies of key retrieved articles. From twenty-six observational studies (cohort or case-control) with ischemic or hemorrhagic strokes the relative risk or odds ratios or hazard ratios of stroke associated with alcohol consumption were reported; alcohol consumption was quantified; and life time abstention (manually estimated where data for current abstainers were given) was used as the reference group. Two reviewers independently extracted the information on study design, participant characteristics, level of alcohol consumption, stroke outcome, control for potential confounding factors, risk estimates and key criteria of study quality using a standardized protocol. Results: The dose-response relationship for hemorrhagic stroke had monotonically increasing risk for increasing consumption, whereas ischemic stroke showed a curvilinear relationship, with a protective effect of alcohol for low to moderate consumption, and increased risk for higher exposure. For more than 3 drinks on average/day, in general women had higher risks than men, and the risks for mortality were higher compared to the risks for morbidity. Conclusions: These results indicate that heavy alcohol consumption increases the relative risk of any stroke while light or moderate alcohol consumption may be protective against ischemic stroke. Preventive measures that should be initiated are discussed. [ABSTRACT FROM AUTHOR]

Aims To analyze the dose–response relationship between average daily alcohol consumption and the risk of hypertension via systematic review and meta-analysis. Design A computer-assisted search was completed for 10 databases, followed by hand searches of relevant articles. Only studies with longitudinal design, quantitative measurement of alcohol consumption and biological measurement of outcome were included. Dose–response relationships were assessed by determining the best-fitting model via first- and second-degree fractional polynomials. Various tests for heterogeneity and publication bias were conducted. Findings A total of 12 cohort studies were identified from the literature from the United States, Japan and Korea. A linear dose–response relationship with a relative risk of 1.57 at 50 g pure alcohol per day and 2.47 at 100 g per day was seen for men. Among women, the meta-analysis indicated a more modest protective effect than reported previously: a significant protective effect was reported for consumption at or below about 5 g per day, after which a linear dose–response relationship was found with a relative risk of 1.81 at 50 g per day and of 2.81 at an average daily consumption of 100 g pure alcohol per day. Among men, Asian populations had higher risks than non-Asian populations. Conclusions The risk for hypertension increases linearly with alcohol consumption, so limiting alcohol intake should be advised for both men and women. [ABSTRACT FROM AUTHOR]

Objective: To clarify the dose-response relationship between alcohol consumption and type 2 diabetes.Research Design and Methods: A systematic computer-assisted and hand search was conducted to identify relevant articles with longitudinal design and quantitative measurement of alcohol consumption. Adjustment was made for the sick-quitter effect. We used fractional polynomials in a meta-regression to determine the dose-response relationships by sex and end point using lifetime abstainers as the reference group.Results: The search revealed 20 cohort studies that met our inclusion criteria. A U-shaped relationship was found for both sexes. Compared with lifetime abstainers, the relative risk (RR) for type 2 diabetes among men was most protective when consuming 22 g/day alcohol (RR 0.87 [95% CI 0.76-1.00]) and became deleterious at just over 60 g/day alcohol (1.01 [0.71-1.44]). Among women, consumption of 24 g/day alcohol was most protective (0.60 [0.52-0.69]) and became deleterious at about 50 g/day alcohol (1.02 [0.83-1.26]).Conclusions: Our analysis confirms previous research findings that moderate alcohol consumption is protective for type 2 diabetes in men and women. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- To clarify the dose-response relationship between alcohol consumption and type 2 diabetes. RESEARCH DESIGN AND METHODS -- A systematic computer-assisted and hand search was conducted to identify relevant articles with longitudinal design and quantitative measurement of alcohol consumption. Adjustment was made for the sick-quitter effect. We used fractional polynomials in a meta-regression to determine the dose-response relationships by sex and end point using lifetime abstainers as the reference group. RESULTS -- The search revealed 20 cohort studies that met our inclusion criteria. A U-shaped relationship was found for both sexes. Compared with lifetime abstainers, the relative risk (RR) for type 2 diabetes among men was most protective when consuming 22 g/day alcohol (RR 0.87 [95% CI 0.76-1.00]) and became deleterious at just over 60 g/day alcohol (1.01 [0.71-1.44]). Among women, consumption of 24 g/day alcohol was most protective (0.60 [0.52-0.69]) and became deleterious at about 50 g/day alcohol (1.02 [0.83-1.26]). CONCLUSIONS -- Our analysis confirms previous research findings that moderate alcohol consumption is protective for type 2 diabetes in men and women. [ABSTRACT FROM AUTHOR]

Driving under the influence of cannabis (DUIC) is detrimental to road safety. Risk perception is a strong determinant of DUIC behaviour, yet little is known about the factors influencing DUIC risk perception in the general population. The objective of this study was to identify factors associated with risk perceptions of motor vehicle collision and legal consequences due to DUIC and examine whether these perceptions were associated with DUIC behaviour. Data were derived from the 2017 CAMH Monitor, a cross-sectional telephone survey of adults aged 18+ years in Ontario, Canada (n = 1813). Multivariable logistic regression analyses were performed. Approximately 90% of adults overall agreed that DUIC increases motor vehicle collision risk compared to 55% of those reporting past-year DUIC. Being male, less educated, and using cannabis at least monthly were associated with disagreeing that DUIC increases motor vehicle collision risk. Being male, young, and using cannabis at least monthly were associated with agreeing that DUIC is safer than driving under the influence of alcohol (DUIA). Being male and using cannabis less than monthly were associated with agreeing that the chances of getting caught for DUIC are higher than DUIA. Safety but not legal risk perceptions were associated with DUIC behaviour among cannabis-using drivers. Cannabis legalization provides a timely opportunity for DUIC prevention strategies. This study suggests that policymakers should target male cannabis users and highlight the safety risks of DUIC. Further research is needed to assess the effectiveness of prevention measures and the impact of cannabis legalization on DUIC perceptions and behaviour. [ABSTRACT FROM AUTHOR]

This updated network meta-analysis aims at exploring whether the concurrent use of midazolam or antiemetics may enhance the efficacy of other pharmacological regimens for delirium prophylaxis in pediatric population after general anesthesia (GA). Network meta-analysis (PROSPERO registration: CRD42020179483). Postoperative recovery area. Pediatric patients undergoing GA with sevoflurane. Pharmacological interventions applied during GA with sevoflurane. This network meta-analysis of randomized controlled trials (RCTs) was conducted with a frequentist model. PubMed, Embase, ProQuest, ScienceDirect, Cochrane CENTRAL, ClinicalKey, Web of Science, and ClinicalTrials.gov were searched from their inception dates to April 12, 2020, for RCTs of either placebo-controlled or active-controlled design containing information on the incidence of emergence delirium in pediatric patients undergoing sevoflurane anesthesia. Seventy studies comprising 6904 participants were included for the analysis of 30 pharmacological interventions. Based on surface under the cumulative ranking curve (SUCRA) analysis, midazolam was ranked the lowest in therapeutic effect (SUCRA: 20%), while antiemetics as a monotherapy had no effect on delirium prophylaxis. However, there was a trend that most combination therapies with midazolam or antiemetics were superior to monotherapies for delirium prophylaxis. Subgroup analyses based on age (i.e., ≤7 years) and a validated scoring system (i.e., the Pediatric Anesthesia Emergence Delirium scale) for delirium also suggested a better efficacy of combination therapies than monotherapies. Overall, combination therapies with midazolam or antiemetics did not have a negative impact on the incidence of postoperative nausea and vomiting, length of stay in the postanesthesia care unit, or time to extubation. The dexmedetomidine-midazolam-antiemetic combination was the most effective strategy for the prevention of emergence delirium. This network meta-analysis suggested that the incorporation of midazolam or antiemetics as adjuncts for combination therapies may have synergistic effects against pediatric postoperative emergence delirium. Future large-scale placebo-controlled RCTs are warranted to validate our findings. • Most combined regimens were better than monotherapies against emergence delirium. • Triple therapies were more effective than dual therapies, followed by monotherapies. • Dexmedetomidine-midazolam-antiemetic combination had the best prophylactic effect. [ABSTRACT FROM AUTHOR]

Study Objective: This updated network meta-analysis aims at exploring whether the concurrent use of midazolam or antiemetics may enhance the efficacy of other pharmacological regimens for delirium prophylaxis in pediatric population after general anesthesia (GA).Design: Network meta-analysis (PROSPERO registration: CRD42020179483).Setting: Postoperative recovery area.Patients: Pediatric patients undergoing GA with sevoflurane.Interventions: Pharmacological interventions applied during GA with sevoflurane.Measurements: This network meta-analysis of randomized controlled trials (RCTs) was conducted with a frequentist model. PubMed, Embase, ProQuest, ScienceDirect, Cochrane CENTRAL, ClinicalKey, Web of Science, and ClinicalTrials.gov were searched from their inception dates to April 12, 2020, for RCTs of either placebo-controlled or active-controlled design containing information on the incidence of emergence delirium in pediatric patients undergoing sevoflurane anesthesia.Main Results: Seventy studies comprising 6904 participants were included for the analysis of 30 pharmacological interventions. Based on surface under the cumulative ranking curve (SUCRA) analysis, midazolam was ranked the lowest in therapeutic effect (SUCRA: 20%), while antiemetics as a monotherapy had no effect on delirium prophylaxis. However, there was a trend that most combination therapies with midazolam or antiemetics were superior to monotherapies for delirium prophylaxis. Subgroup analyses based on age (i.e., ≤7 years) and a validated scoring system (i.e., the Pediatric Anesthesia Emergence Delirium scale) for delirium also suggested a better efficacy of combination therapies than monotherapies. Overall, combination therapies with midazolam or antiemetics did not have a negative impact on the incidence of postoperative nausea and vomiting, length of stay in the postanesthesia care unit, or time to extubation. The dexmedetomidine-midazolam-antiemetic combination was the most effective strategy for the prevention of emergence delirium.Conclusions: This network meta-analysis suggested that the incorporation of midazolam or antiemetics as adjuncts for combination therapies may have synergistic effects against pediatric postoperative emergence delirium. Future large-scale placebo-controlled RCTs are warranted to validate our findings. [ABSTRACT FROM AUTHOR]

• Adult ADHD symptoms are strongly associated with psychological distress. • ADHD symptoms not linked to drinking problems after adjusting for other variables. • ADHD symptoms not associated with gambling problems before or after adjustment. • One of the first studies to assess the role of brain injury in these relationships. Recognition of ADHD in the adult population is relatively recent. Epidemiological research examining the mental health impact of ADHD in adulthood is thus limited. The objective of this study was to examine whether adult ADHD symptoms are associated with psychological distress, hazardous drinking, and problem gambling, after controlling for traumatic brain injury and sociodemographic characteristics. We analyzed data from a population-based survey administered in 2015 and 2016 to adults aged 18 years and over in Ontario, Canada (N = 3,817). Logistic regression was used to construct unadjusted and multivariable models for each of the three focal relationships. In the unadjusted models, ADHD symptoms were significantly related to psychological distress (OR = 9.3; 95% CI:6.1, 14.0) and hazardous drinking (OR = 2.1; 95% CI: 1.3, 3.4), but not to problem gambling (OR = 1.5; 0.5, 4.3). After adjustment, ADHD symptoms were significantly related to psychological distress (OR = 7.1; 95% CI: 4.6, 11.1), but not hazardous drinking (OR = 1.4; 95% CI: 0.8, 2.5) or problem gambling (OR = 0.6; 95% CI: 0.2, 2.5). This study further highlights the importance of clinicians assessing for concomitant ADHD and psychological distress in adults. [ABSTRACT FROM AUTHOR]