The risk relationships between alcohol consumption, alcohol use disorder and alcohol use disorder mortality: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Increasing levels of alcohol use are associated with a risk of developing an alcohol use disorder (AUD), which, in turn, is associated with considerable burden. Our aim was to estimate the risk relationships between alcohol consumption and AUD incidence and mortality. METHOD: A systematic literature search was conducted, using Medline, Embase, PsycINFO and Web of Science for case-control or cohort studies published between 1 January 2000 and 8 July 2022. These were required to report alcohol consumption, AUD incidence and/or AUD mortality (including 100% alcohol-attributable deaths). The protocol was registered with PROSPERO (CRD42022343201). Dose-response and random-effects meta-analyses were used to determine the risk relationships between alcohol consumption and AUD incidence and mortality and mortality rates in AUD patients, respectively. RESULTS: Of the 5904 reports identified, seven and three studies from high-income countries and Brazil met the inclusion criteria for quantitative and qualitative syntheses, respectively. In addition, two primary US data sources were analyzed. Higher levels of alcohol consumption increased the risk of developing or dying from an AUD exponentially. At an average consumption of four standard drinks (assuming 10 g of pure alcohol/standard drink) per day, the risk of developing an AUD was increased sevenfold [relative risk (RR) = 7.14, 95% confidence interval (CI) = 5.13-9.93] and the risk of dying fourfold (RR = 3.94, 95% CI = 3.53-4.40) compared with current non-drinkers. The mortality rate in AUD patients was 3.13 (95% CI = 1.07-9.13) per 1000 person-years. CONCLUSIONS: There are exponential positive risk relationships between alcohol use and both alcohol use disorder incidence and mortality. Even at an average consumption of 20 g/day (about one large beer), the risk of developing an alcohol use disorder (AUD) is nearly threefold that of current non-drinkers and the risk of dying from an AUD is approximately double that of current non-drinkers.

Differential Associations of Alcohol Use With Ischemic Heart Disease Mortality by Socioeconomic Status in the US, 1997-2018.

Importance: People with low socioeconomic status (SES) experience greater burden from alcohol-attributable health conditions and mortality at equal levels of alcohol consumption compared with those with high SES. A U-shaped association has been established between alcohol use and ischemic heart disease (IHD), but no study has explored how such an association differs by SES in the US. Objective: To investigate how the association of alcohol use with ischemic heart disease mortality differs by SES in the general US population. Design, Setting, and Participants: This cohort study used record-linked, cross-sectional National Health Interview Survey data for US adults aged 25 years and older, covering 1997 to 2018 with mortality follow-up until 2019. Data analysis was performed from March to June 2023. Exposures: SES (operationalized using education attainment) and alcohol consumption were obtained from self-reported questionnaires. Main Outcomes and Measures: The outcome was time to IHD mortality or last presumed alive by December 31, 2019. Cox proportional hazard models were applied to evaluate the interaction of SES and alcohol use on IHD mortality, with age as the time scale. Sex-stratified analyses were performed, adjusting for race and ethnicity, marital status, smoking, body mass index, physical activity, and survey year. Fine-Gray subdistribution models were applied to account for competing risks. Results: This cohort study of 524 035 participants (mean [SD] age at baseline, 50.3 [16.2] years; 290 492 women [51.5%]) found a statistically significantly greater protective association of drinking less than 20 g per day (vs lifetime abstinence) with IHD mortality in the high-SES group compared with the low-SES group (interaction term hazard ratio [HR], 1.22 [95% CI, 1.02-1.45] in men; HR, 1.35 [95% CI, 1.09-1.67] in women). In addition, the differential associations of drinking less than 20 g per day with IHD mortality by SES were observed only among people with less than monthly heavy episodic drinking (HED) (interaction term, HR, 1.20 [95% CI, 1.01-1.43] in men; HR, 1.34 [95% CI, 1.08-1.67] in women); no difference was found in people with at least monthly HED. Among women there was a greater protective association of drinking less than 20 g per day with IHD mortality in the high-SES group than the middle-SES group (interaction term, HR, 1.35 [95% CI, 1.06-1.72]). Among men, the harmful association of drinking more than 60 g per day with IHD mortality in the low-SES group was largely explained by other behavioral risk factors (ie, smoking, body mass index, and physical activity). Conclusions and Relevance: This cohort study found a greater protective association between drinking less than 20 g per day with less than monthly HED and IHD mortality in the high-SES group compared with the low-SES group, in both sexes even after adjusting for key covariables and behavioral risk factors. The findings suggest that public health interventions on alcohol use should account for different socioeconomic backgrounds when assessing the level of risk related to alcohol exposure, bearing in mind that levels of consumption deemed safe regarding a specific outcome such as IHD may indeed be less safe or not safe across all sociodemographic groups.

Trajectory of health-related quality of life in parents of children treated with epilepsy surgery versus medical therapy.

PURPOSE: Child health-related quality of life (HRQOL) has been shown to improve after epilepsy surgery and is linked to parent HRQOL. We postulated that the HRQOL of parents whose children underwent epilepsy surgery would improve over two years compared to those treated with medical therapy. The aim of the study was to evaluate the trajectory of HRQOL of parents whose children received treatment with epilepsy surgery or medical therapy over two years. METHODS: This multi-center study recruited parents whose children were evaluated for epilepsy surgery. Parents completed measures of care-related QOL (CarerQOL) at the time of their children's surgical evaluation, 6 months, 1 year, and 2 years later. Additional measures included parent anxiety and depression, satisfaction with family relationships, family resources and demands, and child clinical variables. A linear mixed model was used to compare the trajectories of parent HRQOL of surgical and medical patients, adjusting for baseline clinical, parent, and family characteristics. RESULTS: There were 111 children treated with surgery and 154 with medical therapy. The trajectory of parent HRQOL was similar among parents of surgical and medical patients over the two-year follow-up. However, HRQOL of parents of surgical patients was 3.0 points higher (95%CI - 0.1, 6.1) across the follow-up period compared to parents of medical patients. Parents of seizure-free children reported 2.3 points (95%CI 0.2, 4.4) higher HRQOL relative to parents of non-seizure-free children across the two-year follow-up. CONCLUSION: Parent HRQOL did not improve after their children were treated with epilepsy surgery, possibly related to ongoing comorbidities in children.

Effectiveness of a mindfulness-based intervention for persons with early psychosis: A multi-site randomized controlled trial.

BACKGROUND: The Mindfulness Ambassador Program (MAP) is a group-based, facilitated mindfulness-based intervention (MBI). We sought to determine the effectiveness of MAP on reducing negative psychotic symptoms and enhancing mindfulness skills among persons experiencing early psychosis. METHODS: We conducted a pragmatic randomized controlled trial (RCT) at three early psychosis intervention (EPI) programs in Ontario, Canada. Participants (N = 59) were randomly assigned to receive MAP (n = 29) for 1-hour weekly sessions over 3 months, or to treatment as usual (TAU, n = 30). Assessments were conducted at baseline, 3 months, and 6 months using the Self-Evaluation of Negative Symptoms (SNS) and Kentucky Inventory of Mindfulness Skills (KIMS). Linear mixed methods were used to assess the joint effects of group and time. RESULTS: At 3 months, participants who received MAP (n = 17) demonstrated greater reductions on the SNS relative to TAU (n = 15), which were clinically and statistically significant (-4.1; 95%CI -7.5, -0.7; p = 0.019). At 6 months, the difference between MAP (n = 10) and TAU (n = 13) was no longer statistically significant (-1.2; 95%CI -5.2,2.7; p = 0.54). On the KIMS, no significant effects were found at 3 months (+0.3; 95%CI -2.0,2.5; p = 0.82) or 6 months (+0.4; 95%CI -2.2,2.9; p = 0.79). CONCLUSIONS: We conducted one of the first multi-site RCTs of a MBI for early psychosis. Our findings indicated that MAP was more effective in reducing negative symptoms compared to TAU in the short term. Earlier reductions in negative psychotic symptoms may help facilitate recovery in the long term.

How does alcohol use impact morbidity and mortality of liver cirrhosis? A systematic review and dose-response meta-analysis.

BACKGROUND: Alcohol consumption is the most important risk factor responsible for the disease burden of liver cirrhosis (LC). Estimates of risk relationships available usually neither distinguish between different causes such as alcohol-related LC or hepatitis-related LC, nor differentiate between morbidity and mortality as outcome. We aimed to address this research gap and identify dose-response relationships between alcohol consumption and LC, by cause and outcome. METHODS: A systematic review using PubMed/Medline and Embase was conducted, identifying studies that reported an association between level of alcohol use and LC. Meta-regression models were used to estimate the dose-response relationships and control for heterogeneity. RESULTS: Totally, 44 studies, and 1 secondary data source, with a total of 5,122,534 participants and 15,150 cases were included. Non-linear dose-response relationships were identified, attenuated for higher levels of consumption. For morbidity, drinking 25 g/day was associated with a RR of 1.81 (95% CI 1.68-1.94) compared to lifetime abstention; 50 g/day and 100 g/day corresponded to 3.54 (95% CI 3.29-3.81) and 8.15 (95% CI 7.46-8.91), respectively. For mortality, for 25 g/day, a RR of 2.65 (95% CI 2.22-3.16); for 50 g/day, a RR of 6.83 (95% CI 5.84-7.97); for 100 g/day, a RR of 16.38 (95% CI 13.81-19.42) were identified. A higher risk for alcohol-related and all-cause LC as compared to hepatitis C-related LC was found. CONCLUSION: Our results demonstrated higher acceleration for mortality compared to morbidity. The current findings will inform the way we quantify the burden due to LC attributable to alcohol use.

Trajectories of parent well-being in children with drug-resistant epilepsy.

OBJECTIVE: This longitudinal cohort study aimed to identify trajectories of parent well-being over the first 2 years after their child's evaluation for candidacy for epilepsy surgery, and to identify the baseline clinical and demographic characteristics associated with these trajectories. Parent well-being was based on parent depressive and anxiety symptoms and family resources (i.e., family mastery and social support). METHODS: Parents of 259 children with drug-resistant epilepsy (105 of whom eventually had surgery) were recruited from eight epilepsy centers across Canada at the time of their evaluation for epilepsy surgery candidacy. Participants were assessed at baseline and 6-month, 1-year, and 2-year follow-up. The trajectories of parents' depressive symptoms, anxiety symptoms, and family resources were jointly estimated using multigroup latent class growth models. RESULTS: The analyses identified three trajectories: an optimal-stable group with no/minimal depressive or anxiety symptoms, and high family resources that remained stable over time; a mild-decreasing-plateau group with mild depressive and anxiety symptoms that decreased over time then plateaued, and intermediate family resources that remained stable; and a moderate-decreasing group with moderate depressive and anxiety symptoms that decreased slightly, and low family resources that remained stable over time. Parents of children with higher health-related quality of life, fathers, and parents who had higher household income were more likely to have better trajectories of well-being. Treatment type was not associated with the trajectory groups, but parents whose children were seizure-free at the time of the last follow-up were more likely to have better trajectories (optimal-stable or mild-decreasing-plateau trajectories). SIGNIFICANCE: This study documented distinct trajectories of parent well-being, from the time of the child's evaluation for epilepsy surgery. Parents who present with anxiety and depressive symptoms and low family resources do not do well over time. They should be identified and offered supportive services early in their child's epilepsy treatment history.

Pre-Operative Predictors of Health-Related Quality of Life Two Years After Pediatric Epilepsy Surgery: A Prospective Cohort Study.

PURPOSE: Seizure freedom is an important predictor of health-related quality of life (HRQOL) after pediatric epilepsy surgery. This study aimed to identify the pre-operative predictors of HRQOL 2 years after epilepsy surgery in children with drug-resistant epilepsy. METHODS: This multicenter prospective cohort study assessed pre-operative predictors including child (demographics and clinical variables), caregiver (including caregiver depressive and anxiety symptoms) and family characteristics. HRQOL was assessed using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE)-55 pre-operatively and 2-years after surgery. Univariable linear regression analyses were done to identify significant preoperative predictors of HRQOL 2-years after surgery, followed by multivariable regression. RESULTS: Ninety-five children underwent surgery, mean age was 11.4 (SD=4.2) years, and 59 (62%) were male. Mean QOLCE scores were 57.4 (95%CI: 53.8, 61.0) pre-operatively and 65.6 (95%CI: 62.0, 69.1) after surgery. Univariable regression showed fewer anti-seizure medications (ß=-6.1 [95%CI: -11.2, -1.0], p = 0.019), older age at seizure onset (ß=1.6 [95%CI: 0.8, 2.4], p<0.001), higher pre-operative HRQOL (ß=0.7 [95%CI: 0.5, 0.8], p<0.001), higher family resources (ß=0.6 [95%CI: 0.3, 0.9], p<0.001), better family relationships (ß=1.7 [95%CI: 0.3, 3.1], p = 0.017) and lower family demands (ß=-0.9 [95%CI: -1.5, -0.4], p<0.001) were associated with higher HRQOL after surgery. Caregiver characteristics did not predict HRQOL after surgery (p>0.05). Multivariable regression showed older age at seizure onset (ß=4.6 [95%CI: 1.6, 7.6], p = 0.003) and higher pre-operative HRQOL (ß=10.2 [95%CI: 6.8, 13.6], p<0.001) were associated with higher HRQOL after surgery. CONCLUSION: This study underscores the importance of optimizing pre-operative HRQOL to maximize HRQOL outcome after pediatric epilepsy surgery.

Can lifestyle factors explain racial and ethnic inequalities in all-cause mortality among US adults?

BACKGROUND: Racial and ethnic inequalities in all-cause mortality exist, and individual-level lifestyle factors have been proposed to contribute to these inequalities. In this study, we evaluate the extent to which the association between race and ethnicity and all-cause mortality can be explained by differences in the exposure and vulnerability to harmful effects of different lifestyle factors. METHODS: The 1997-2014 cross-sectional, annual US National Health Interview Survey (NHIS) linked to the 2015 National Death Index was used. NHIS reported on race and ethnicity (non-Hispanic White, non-Hispanic Black, and Hispanic/Latinx), lifestyle factors (alcohol use, smoking, body mass index, physical activity), and covariates (sex, age, education, marital status, survey year). Causal mediation using an additive hazard and marginal structural approach was used. RESULTS: 465,073 adults (18-85 years) were followed 8.9 years (SD: 5.3); 49,804 deaths were observed. Relative to White adults, Black adults experienced 21.7 (men; 95%CI: 19.9, 23.5) and 11.5 (women; 95%CI: 10.1, 12.9) additional deaths per 10,000 person-years whereas Hispanic/Latinx women experienced 9.3 (95%CI: 8.1, 10.5) fewer deaths per 10,000 person-years; no statistically significant differences were identified between White and Hispanic/Latinx men. Notably, these differences in mortality were partially explained by both differential exposure and differential vulnerability to the lifestyle factors among Black women, while different effects of individual lifestyle factors canceled each other out among Black men and Hispanic/Latinx women. CONCLUSIONS: Lifestyle factors provide some explanation for racial and ethnic inequalities in all-cause mortality. Greater attention to structural, life course, healthcare, and other factors is needed to understand determinants of inequalities in mortality and to advance health equity.

Reducing alcohol use through alcohol control policies in the general population and population subgroups: a systematic review and meta-analysis.

We estimate the effects of alcohol taxation, minimum unit pricing (MUP), and restricted temporal availability on overall alcohol consumption and review their differential impact across sociodemographic groups. Web of Science, Medline, PsycInfo, Embase, and EconLit were searched on 08/12/2022 and 09/26/2022 for studies on newly introduced or changed alcohol policies published between 2000 and 2022 (Prospero registration: CRD42022339791). We combined data using random-effects meta-analyses. Risk of bias was assessed using the Newcastle-Ottawa Scale. Of 1887 reports, 36 were eligible. Doubling alcohol taxes or introducing MUP (Int$ 0.90/10 g of pure alcohol) reduced consumption by 10% (for taxation: 95% prediction intervals [PI]: -18.5%, -1.2%; for MUP: 95% PI: -28.2%, 5.8%), restricting alcohol sales by one day a week reduced consumption by 3.6% (95% PI: -7.2%, -0.1%). Substantial between-study heterogeneity contributes to high levels of uncertainty and must be considered in interpretation. Pricing policies resulted in greater consumption changes among low-income alcohol users, while results were inconclusive for other socioeconomic indicators, gender, and racial and ethnic groups. Research is needed on the differential impact of alcohol policies, particularly for groups bearing a disproportionate alcohol-attributable health burden. Funding: Research reported in this publication was supported by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under Award Number R01AA028009.

A longitudinal cohort study of mediators of health-related quality of life after pediatric epilepsy surgery or medical treatment.

OBJECTIVES: The purpose of this longitudinal cohort study was to examine the variables that influence health-related quality of life (HRQOL) after epilepsy surgery in children. We examined whether treatment type (surgical vs medical therapy) and seizure control are related to other variables that have been shown to influence HRQOL, namely depressive symptoms in children with epilepsy or their parents, and the availability of family resources. METHODS: In total, 265 children with drug-resistant epilepsy were recruited from eight epilepsy centers across Canada at the time of their evaluation for candidacy for epilepsy surgery and were assessed at baseline, 6-month, 1-year, and 2-year follow-up. Parents completed the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) and measures of family resources and depression; children completed depression inventories. Causal mediation analyses using natural effect models were used to evaluate the extent to which the relationship between treatment and HRQOL was explained by seizure control, child and parent depressive symptoms, and family resources. RESULTS: Overall, 111 children underwent surgery and 154 were treated with medical therapy only. The HRQOL scores of surgical patients were 3.4 points higher (95% confidence interval [CI]: -0.2, 7.0) relative to medical patients at the 2-year follow-up after adjusting for baseline covariates, with 66% of the effect of surgery attributed to seizure control. Child or parent depressive symptoms and family resources had negligible mediation effects between treatment and HRQOL. The effect of seizure control on HRQOL was not mediated by child or parent depressive symptoms, or by family resources. SIGNIFICANCE: The findings demonstrate that seizure control is on the causal pathway between epilepsy surgery and improved HRQOL in children with drug-resistant epilepsy. However, child and parent depressive symptoms and family resources were not significant mediators. The results highlight the importance of achieving seizure control to improve HRQOL.

Can lifestyle factors explain racial and ethnic inequalities in all-cause mortality among US adults?

Background: Racial and ethnic inequalities in all-cause mortality exist, and individual-level lifestyle factors have been proposed to contribute to these inequalities. In this study, we evaluate the extent to which the association between race and ethnicity and all-cause mortality can be explained by differences in the exposure and vulnerability to harmful effects of different lifestyle factors. Methods: The 1997-2014 cross-sectional, annual US National Health Interview Survey (NHIS) linked to the 2015 National Death Index was used. NHIS reported on race and ethnicity (non-Hispanic White, non-Hispanic Black, and Hispanic/Latinx), lifestyle factors (alcohol use, smoking, body mass index, physical inactivity), and covariates (sex, age, education, marital status, survey year). Causal mediation using an additive hazard and marginal structural approach was used. Results: 465,073 adults (18-85 years) were followed 8.9 years (SD:5.3); 49,804 deaths were observed. Relative to White adults, Black adults experienced 21.7 (men; 95%CI: 19.9, 23.5) and 11.5 (women; 95%CI: 10.1, 12.9) additional deaths per 10,000 person-years whereas Hispanic/Latinx women experienced 9.3 (95%CI: 8.1, 10.5) fewer deaths per 10,000 person-years; no statistically significant differences were identified between White and Hispanic/Latinx men. Notably, these differences in mortality were partially explained by both differential exposure and differential vulnerability to these lifestyle factors among Black women, while different effects of individual lifestyle factors canceled each other out among Black men and Hispanic/Latinx women. Conclusions: Lifestyle factors provide some explanation for racial and ethnic inequalities in all-cause mortality. Greater attention to structural, life course, healthcare, and other factors is needed to understand determinants of inequalities in mortality and advance health equity.

Trajectory of Health-Related Quality of Life After Pediatric Epilepsy Surgery.

Importance: Health-related quality of life (HRQOL) is regarded as a key outcome for evaluating treatment efficacy. However, it is uncertain how HRQOL evolves after epilepsy surgery compared with medical therapy, such as whether it continues to improve over time, improves and then remains stable, or deteriorates after a period of time. Objective: To assess trajectory of HRQOL over 2 years in children with drug-resistant epilepsy (DRE) treated with surgery compared with medical therapy. Design, Setting, and Participants: Prospective cohort study assessing HRQOL longitudinally over 2 years. Participants were children recruited from 8 epilepsy centers in Canada from 2014 to 2019 with suspected DRE aged 4 to 18 years who were evaluated for surgery. Data were analyzed from May 2014 to December 2021. Exposures: Epilepsy surgery or medical therapy. Main Outcomes and Measures: HRQOL was measured using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE)-55. HRQOL and seizure frequency were assessed at baseline, 6-month, 1-year, and 2-year follow-ups. Clinical, parent, and family characteristics were assessed at baseline. A linear mixed model was used to evaluate HRQOL over time, adjusting for baseline clinical, parent, and family characteristics. Results: There were 111 surgical and 154 medical patients (mean [SD] age at baseline was 11.0 [4.1] years; 118 [45%] were female). At baseline, HRQOL was similar among surgical and medical patients. HRQOL of surgical patients was 3.0 (95% CI, -0.7 to 6.8) points higher at 6-month, 4.9 (95% CI, 0.7 to 9.1) points higher at 1-year, and 5.1 (95% CI, 0.7 to 9.5) points higher at 2-year follow-ups compared with medical patients. Surgical patients experienced greater improvements in social functioning relative to medical patients, but not for cognitive, emotional, and physical functioning. At 2-year follow-up, 72% of surgical patients were seizure-free, compared with 33% of medical patients. Seizure-free patients reported higher HRQOL than those who were not. Conclusions and Relevance: This study provided evidence on the association between epilepsy surgery and children's HRQOL, with improvement in HRQOL occurring within the first year and remaining stable 2 years after surgery. By demonstrating that surgery improved seizure freedom and HRQOL, which has downstream effects such as better educational attainment, reduced health care resource utilization, and health care cost, these findings suggest that the high costs of surgery are justified, and that improved access to epilepsy surgery is necessary.

Evaluating the Quality of Written Feedback Within Entrustable Professional Activities in an Internal Medicine Cohort.

Background: Whether written comments in entrustable professional activities (EPAs) translate into high-quality feedback remains uncertain. Objective: We aimed to evaluate the quality of EPA feedback completed by faculty and senior residents. Methods: Using retrospective descriptive analysis, we assessed the quality of feedback from all EPAs for 34 first-year internal medicine residents from July 2019 to May 2020 at Western University in London, Ontario, Canada. We assessed feedback quality on 4 domains: timeliness, task orientation, actionability, and polarity. Four independent reviewers were blinded to names of evaluators and learners and were randomized to assess each EPA for the 4 domains. Statistical analyses were completed using R 3.6.3. Chi-square or Fisher's exact test and Cochran-Armitage test for trend were used to compare the quality of feedback provided by faculty versus student assessors, and to compare the effect of timely versus not timely feedback on task orientation, actionability, and polarity. Results: A total of 2471 EPAs were initiated by junior residents. Eighty percent (n=1981) of these were completed, of which 61% (n=1213) were completed by senior residents. Interrater reliability was almost perfect for timeliness (κ=0.99), moderate for task orientation (κ=0.74), strong for actionability (κ=0.81), and moderate for polarity (κ=0.62). Of completed EPAs, 47% (n=926) were timely, 85% (n=1697) were task oriented, 83% (n=1649) consisted of reinforcing feedback, 4% (n=79) contained mixed feedback, and 12% (n=240) had neutral feedback. Thirty percent (n=595) were semi- or very actionable. Conclusions: The written feedback in the EPAs was task oriented but was neither timely nor actionable. The majority of EPAs were completed by senior residents rather than faculty.

Simulation of Alcohol Control Policies for Health Equity (SIMAH) Project: Study Design and First Results.

Since about 2010, life expectancy at birth in the United States has stagnated and begun to decline, with concurrent increases in the socioeconomic divide in life expectancy. The Simulation of Alcohol Control Policies for Health Equity (SIMAH) Project uses a novel microsimulation approach to investigate the extent to which alcohol use, socioeconomic status (SES), and race/ethnicity contribute to unequal developments in US life expectancy and how alcohol control interventions could reduce such inequalities. Representative, secondary data from several sources will be integrated into one coherent, dynamic microsimulation to model life-course changes in SES and alcohol use and cause-specific mortality attributable to alcohol use by SES, race/ethnicity, age, and sex. Markov models will be used to inform transition intensities between levels of SES and drinking patterns. The model will be used to compare a baseline scenario with multiple counterfactual intervention scenarios. The preliminary results indicate that the crucial microsimulation component provides a good fit to observed demographic changes in the population, providing a robust baseline model for further simulation work. By demonstrating the feasibility of this novel approach, the SIMAH Project promises to offer superior integration of relevant empirical evidence to inform public health policy for a more equitable future.

Seizure outcome of pediatric magnetic resonance-guided laser interstitial thermal therapy versus open surgery: A matched noninferiority cohort study.

OBJECTIVE: Minimally invasive magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has been proposed as an alternative to open epilepsy surgery, to address concerns regarding the risk of open surgery. Our primary hypothesis was that seizure freedom at 1 year after MRgLITT is noninferior to open surgery in children with drug-resistant epilepsy (DRE). The secondary hypothesis was that MRgLITT has fewer complications and shorter hospitalization than surgery. The primary objective was to compare seizure outcome of MRgLITT to open surgery in children with DRE. The secondary objective was to compare complications and length of hospitalization of the two treatments. METHODS: This retrospective multicenter cohort study included children with DRE treated with MRgLITT or open surgery with 1-year follow-up. Exclusion criteria were corpus callosotomy, neurostimulation, multilobar or hemispheric surgery, and lesion with maximal dimension > 60 mm. MRgLITT patients were propensity matched to open surgery patients. The primary outcome was seizure freedom at 1 year posttreatment. The difference in seizure freedom was compared using noninferiority test, with noninferiority margin of -10%. The secondary outcomes were complications and length of hospitalization. RESULTS: One hundred eighty-five MRgLITT patients were matched to 185 open surgery patients. Seizure freedom at 1 year follow-up was observed in 89 of 185 (48.1%) MRgLITT and 114 of 185 (61.6%) open surgery patients (difference = -13.5%, one-sided 97.5% confidence interval = -23.8% to ∞, pNoninferiority  = .79). The lower confidence interval boundary of -23.8% was below the prespecified noninferiority margin of -10%. Overall complications were lower in MRgLITT compared to open surgery (10.8% vs. 29.2%, respectively, p < .001). Hospitalization was shorter for MRgLITT than open surgery (3.1 ± 2.9 vs. 7.2 ± 6.1 days, p < .001). SIGNIFICANCE: Seizure outcome of MRgLITT at 1 year posttreatment was inferior to open surgery. However, MRgLITT has the advantage of better safety profile and shorter hospitalization. The findings will help counsel children and parents on the benefits and risks of MRgLITT and contribute to informed decision-making on treatment options.

Behavioral stability of alcohol consumption and socio-demographic correlates of change among a nationally representative cohort of US adults.

AIMS: To estimate the probability of transitioning between different categories of alcohol use (drinking states) among a nationally representative cohort of United States (US) adults and to identify the effects of socio-demographic characteristics on those transitions. DESIGN, SETTING AND PARTICIPANTS: Secondary analysis of data from the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC), a prospective cohort study conducted in 2001-02 and 2004-05; a US nation-wide, population-based study. Participants included 34 165 adults (mean age = 45.1 years, standard deviation = 17.3; 52% women). MEASUREMENTS: Alcohol use was self-reported and categorized based on the grams consumed per day: (1) non-drinker (no drinks in past 12 months), (2) category I (women = ≤ 20; men = ≤ 40), (3) category II (women = 21-40; men = 41-60) and (4) category III (women = ≥ 41; men = ≥ 61). Multi-state Markov models estimated the probability of transitioning between drinking states, conditioned on age, sex, race/ethnicity and educational attainment. Analyses were repeated with alcohol use categorized based on the frequency of heavy episodic drinking. FINDINGS: The highest transition probabilities were observed for staying in the same state; after 1 year, the probability of remaining in the same state was 90.1% [95% confidence interval (CI) = 89.7%, 90.5%] for non-drinkers, 90.2% (95% CI = 89.9%, 90.5%) for category I, 31.8% (95% CI = 29.7, 33.9%) category II and 52.2% (95% CI = 46.0, 58.5%) for category III. Women, older adults, and non-Hispanic Other adults were less likely to transition between drinking states, including transitions to lower use. Adults with lower educational attainment were more likely to transition between drinking states; however, they were also less likely to transition out of the 'weekly HED' category. Black adults were more likely to transition into or stay in higher use categories, whereas Hispanic/Latinx adults were largely similar to White adults. CONCLUSIONS: In this study of alcohol transition probabilities, some demographic subgroups appeared more likely to transition into or persist in higher alcohol consumption states.

Trends in mortality from alcohol, opioid, and combined alcohol and opioid poisonings by sex, educational attainment, and race and ethnicity for the United States 2000-2019.

BACKGROUND: The ongoing opioid epidemic and increases in alcohol-related mortality are key public health concerns in the USA, with well-documented inequalities in the degree to which groups with low and high education are affected. This study aimed to quantify disparities over time between educational and racial and ethnic groups in sex-specific mortality rates for opioid, alcohol, and combined alcohol and opioid poisonings in the USA. METHODS: The 2000-2019 Multiple Cause of Death Files from the National Vital Statistics System (NVSS) were used alongside population counts from the Current Population Survey 2000-2019. Alcohol, opioid, and combined alcohol and opioid poisonings were assigned using ICD-10 codes. Sex-stratified generalized least square regression models quantified differences between educational and racial and ethnic groups and changes in educational inequalities over time. RESULTS: Between 2000 and 2019, there was a 6.4-fold increase in opioid poisoning deaths, a 4.6-fold increase in combined alcohol and opioid poisoning deaths, and a 2.1-fold increase in alcohol poisoning deaths. Educational inequalities were observed for all poisoning outcomes, increasing over time for opioid-only and combined alcohol and opioid mortality. For non-Hispanic White Americans, the largest educational inequalities were observed for opioid poisonings and rates were 7.5 (men) and 7.2 (women) times higher in low compared to high education groups. Combined alcohol and opioid poisonings had larger educational inequalities for non-Hispanic Black men and women (relative to non-Hispanic White), with rates 8.9 (men) and 10.9 (women) times higher in low compared to high education groups. CONCLUSIONS: For all types of poisoning, our analysis indicates wide and increasing gaps between those with low and high education with the largest inequalities observed for opioid-involved poisonings for non-Hispanic Black and White men and women. This study highlights population sub-groups such as individuals with low education who may be at the highest risk of increasing mortality from combined alcohol and opioid poisonings. Thereby the findings are crucial for the development of targeted public health interventions to reduce poisoning mortality and the socioeconomic inequalities related to it.

Different drugs, different sides: injection use of opioids alone, and not stimulants alone, predisposes to right-sided endocarditis.

OBJECTIVES: Many studies suggest that infective endocarditis (IE) in people who inject drugs is predominantly right sided, while other studies suggest left sided disease; few have differentiated by class of drug used. We hypothesised that based on differing physiological mechanisms, opioids but not stimulants would be associated with right sided IE. METHODS: A retrospective case series of 290 adult (age ≥18) patients with self-reported recent injection drug use, admitted for a first episode of IE to one of three hospitals in London Ontario between April 2007 and March 2018, stratified patients by drug class used (opioid, stimulant or both), and by site of endocarditis. Other outcomes captured included demographics, causative organisms, cardiac and non-cardiac complications, referral to addiction services, medical versus surgical management, and survival. RESULTS: Of those who injected only opioids, 47/71 (69%) developed right-sided IE, 17/71 (25%) developed left-sided IE and 4/71 (6%) had bilateral IE. Of those who injected only stimulants, 11/24 (46%) developed right-sided IE, 11/24 (46%) developed left-sided IE and 2/24 (8%) had bilateral IE. Relative to opioid-only users, stimulant-only users were 1.75 (95% CI 1.05 to 2.93; p=0.031) times more likely to have a left or bilateral IE versus right IE. CONCLUSIONS: While injection use of opioids is associated with a strong predisposition to right-sided IE, stimulants differ in producing a balanced ratio of right and left-sided disease. As the epidemic of crystal methamphetamine injection continues unabated, the rate of left-sided disease, with its attendant higher morbidity and mortality, may also grow.

Impact of number of anti-seizure medications on long-term health-related quality of life in children with epilepsy: A prospective cohort study.

PURPOSE: Health-related quality of life (HRQL) is compromised in children with epilepsy. We aimed to determine whether children diagnosed with epilepsy between ages 4-12 years who are exposed to a higher number of anti-seizure medication (ASM) over the first 2 years, have poorer HRQL 10 years after diagnosis. METHODS: Data were obtained from 195 children enrolled in the Health-Related Quality of Life in Children with Epilepsy Study (HERQULES) in Canada. HRQL was measured using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) completed by parents at baseline through to 10 years after diagnosis. The total number of ASM were reported by physicians four times in the first two years after diagnosis. Multivariable block-wise linear regression was used to assess the impact of ASM (categorized as none, one, or more than one), as well as clinical and family factors on children's HRQL 10 years after diagnosis. RESULTS: Children had a mean age of 7.9 ± 2.3 years at diagnosis and 92 (47%) were female. Mean QOLCE at baseline and 10 years was 72.04±14 and 78.7±16,respectively. Clinically meaningful improvement in HRQL from the 2 to 10-year follow-up was detected in 35% of children, reported similarly across all ASM treatment categories (p = .38). The number of ASM prescribed in the first two years was associated with HRQL at the 10-year follow-up, however this association was not significant when adjusting for clinical characteristics, family factors, and HRQL at the two-year follow-up (p = .75). Our data showed that HRQL at 2 years was the only variable associated with better HRQL scores at 10 years (p = <.001). CONCLUSION: In children with new onset epilepsy, exposure to a higher number of ASM, when accounting for clinical and family factors as well as HRQL at 2 years, is not independently associated with lower long-term HRQL. Early HRQL was found to be a good indicator of long-term HRQL, despite the number of ASMs prescribed.

Educational Attainment and Lifestyle Risk Factors Associated With All-Cause Mortality in the US.

IMPORTANCE: The US has experienced increasing socioeconomic inequalities and stagnating life expectancy. Past studies have not disentangled 2 mechanisms thought to underlie socioeconomic inequalities in health, differential exposure and differential vulnerability, that have different policy implications. OBJECTIVE: To evaluate the extent to which the association between socioeconomic status (SES) and all-cause mortality can be decomposed into a direct effect of SES, indirect effects through lifestyle factors (differential exposure), and joint effects of SES with lifestyle factors (differential vulnerability). DESIGN SETTING AND PARTICIPANTS: This nationwide, population-based cohort study used the cross-sectional US National Health Interview Survey linked to the National Death Index. Civilian, noninstitutionalized US adults aged 25 to 84 years were included from the 1997 to 2014 National Health Interview Survey and were followed up until December 31, 2015. Data were analyzed from May 1 to October 31, 2021. A causal mediation model using an additive hazard and marginal structural approach was used. EXPOSURES: Both SES (operationalized as educational attainment) and lifestyle risk factors (smoking, alcohol use, obesity, and physical inactivity) were assessed using self-reported questionnaires. MAIN OUTCOMES AND MEASURES: Time to all-cause mortality. RESULTS: Participants included 415 764 adults (mean [SD] age, 49.4 [15.8] years; 55% women; 64% non-Hispanic White), of whom 45% had low educational attainment and 27% had high educational attainment. Participants were followed up for a mean (SD) of 8.8 (5.2) years during which 49 096 deaths (12%) were observed. Low educational attainment (compared with high) was associated with 83.6 (men; 95% CI, 81.8-85.5) and 54.8 (women; 95% CI, 53.4-56.2) additional deaths per 10 000 person-years, of which 66% (men) and 80% (women) were explained by lifestyle factors. Inequalities in mortality were primarily a result of greater exposure and clustering of unhealthy lifestyle factors among low SES groups; with some exceptions among women, little evidence of differential vulnerability was identified. CONCLUSIONS AND RELEVANCE: In this cohort study, differential exposure to lifestyle risk factors was an important mediator of socioeconomic inequalities in mortality. Public health interventions are needed, particularly among low SES groups, to address smoking, physical inactivity, alcohol use, and the socioenvironmental contexts within which these risk factors develop.