Forecasting the impact of means restriction on the suicide mortality rate in the Region of the Americas: an ecological modeling study.

Background: The suicide mortality rate has been increasing in Region of the Americas, despite decreasing in all other World Health Organization (WHO) regions. Means restriction is an effective evidence-based intervention for suicide prevention. The objective of the current study was to estimate the impact of implementing national-level means restriction policies (i.e., firearm and pesticide restrictions) on the suicide mortality rate in the Region of the Americas. Methods: In this ecological modeling study, two counterfactual scenarios were investigated using sex-specific suicide mortality data from the WHO Global Health Estimates database for 2000 to 2019. Forecasted sex-specific age-standardized suicide mortality rates were then estimated for each country for 2020 to 2030. Counterfactual scenario 1 involved modeling the impact of a firearm or pesticide restriction implemented in 2020 for those countries where the respective means accounted for 40% or more of all suicides for at least one sex in 2019, while in counterfactual scenario 2 this threshold was reduced to 20% or more. Findings: It was estimated that if a firearm or pesticide restriction had been implemented in 2020 in those countries where the respective means accounted for 40% or more of all suicides for at least one sex in 2019, by 2030 the male and female suicide mortality rate in the Region of the Americas would be 20.5% (from 14.5 [95% Confidence Interval [CI]: 14.1, 15.0] per 100,000 males to 11.5 [95% CI: 11.1, 12.0] per 100,000 males) and 11.1% (from 4.5 [95% CI: 4.4, 4.7] per 100,000 females to 4.0 [95% CI: 3.9, 4.2] per 100,000 females) lower than the rate if no such restrictions were implemented, respectively. When the threshold was reduced to 20% or more, minimal additional gains in terms of number of suicides avoided and suicide mortality rate reduction would be achieved. Interpretation: The implementation of a firearm or pesticide restriction policy in countries where the respective means account for a large proportion of suicides (e.g., at least 40%) could aid the Region of the Americas in achieving the WHO target of a one third reduction in the suicide mortality rate by 2030. Funding: This work received no funding.

The impact of COVID-19-related national lockdowns on alcohol-related traffic collisions, injuries, and fatalities in Lithuania.

BACKGROUND: The national lockdowns that occurred all over the world in response to the Coronavirus Disease 2019 (COVID-19) pandemic have been found to have impacted alcohol use. The aim was to evaluate the impact of COVID-19-related national lockdowns on alcohol-related traffic collisions, injuries, and fatalities in Lithuania. METHODS: Using monthly data from the Lithuanian Road Police Service for January 2004 to December 2022, we performed interrupted time-series analyses using a generalized additive model to evaluate the impact of COVID-19-related national lockdowns on alcohol-related traffic collisions, injuries, and fatalities. In Lithuania, the COVID-19-related lockdowns occurred from March 2020 to June 2020 and from November 2020 to June 2021. RESULTS: Although overall rates for traffic collisions and injuries decreased during the COVID-19-related lockdowns in Lithuania, these lockdowns were associated with a 3.21% (95% CI: 1.19%, 5.23%) increase in the relative proportion of alcohol-related traffic collisions and a 2.46% (95% CI: 0.12%, 4.80%) increase in the relative proportion of alcohol-related traffic injuries. The association between the lockdowns and alcohol-related traffic fatalities was not statistically significant. CONCLUSION: The COVID-19-related national lockdowns in Lithuania were associated with a decrease in the overall rate of traffic collisions and injuries, but an increase in the relative proportion of alcohol-related traffic collisions and injuries.

Trend of alcohol use disorder as a percentage of all-cause mortality in North America.

OBJECTIVE: To evaluate the trend of alcohol use disorder (AUD) mortality as a percentage of all-cause mortality in Canada and the United States (US) between 2000 and 2019, by age group. RESULTS: Joinpoint regression showed that AUD mortality as a percentage of all-cause mortality significantly increased between 2000 and 2019 in both countries, and across all age groups (i.e., young adults (20-34 years), middle-aged adults (35-49 years), and older adults (50 + years)). The trend has been levelling off, and even reversing in some cases, in recent years. The average annual percentage change differed across countries and between age groups, with a greater increase among Canadian adults aged 35-49 years and among adults aged 50 + years in the US. Over the past two decades, AUD mortality as a percentage of all-cause mortality has been increasing among all adults in both Canada and the US.

Interrupted Time Series Design and Analyses in Health Policy Assessment.

Interrupted time series design is a quasi-experimental study design commonly used to evaluate the impact of a particular intervention (e.g., a health policy implementation) on a specific outcome. Two of the most often recommended analytical approaches to interrupted time series analysis are autoregressive integrated moving average (ARIMA) and Generalized Additive Models (GAM). We conducted simulation tests to determine the performance differences between ARIMA and GAM methodology across different policy effect sizes, with or without seasonality, and with or without misspecification of policy variables. We found that ARIMA exhibited more consistent results under certain conditions, such as with different policy effect sizes, with or without seasonality, while GAM were more robust when the model was misspecified. Given these findings, the variation between the models underscores the need for careful model selection and validation in health policy studies.

Evaluation of the risk relationship between average alcohol volume consumed and suicide in the USA: an analysis of mortality linked cohort data.

OBJECTIVE: Alcohol use disorder is an established risk factor for suicide; however, it is largely unknown whether subclinical levels of drinking may also contribute to the risk of suicide. The objective was to evaluate the relationship between average alcohol volume consumed per day and suicide. METHODS: Data from the annual, cross-sectional National Health Interview Survey, 1997-2018 in the USA, was obtained and linked to the 2019 National Death Index. The association between average alcohol volume consumed in grams per day (g/day) and suicide was quantified using Cox proportional hazards model (multiplicative) and Aalen's additive hazard model. All analyses were stratified by sex, and adjusted for education, marital status, psychological distress, race and ethnicity, and survey year. RESULTS: On the multiplicative scale, for males, former drinkers and those who consumed on average >40-60 g/day had about 43% (HR=1.43, 95% CI 1.03, 2.01) and 72% (HR=1.72, 95% CI 1.14, 2.60) greater risk of dying by suicide, compared with lifetime abstainers, respectively. There was no significant association found for former or current drinkers among females, on the multiplicative scale. On the additive scale, for males, drinking >40-60 g/day on average was associated with 22.7 (95% CI 6.0, 39.4) additional deaths per 100 000 person-years, while for females, being a former drinker and drinking >0-20 g/day on average was associated with 5.5 (95% CI 0.7, 10.4) and 1.9 (95% CI 0.2, 3.5) additional deaths per 100 000 person-years, compared with lifetime abstainers. The level of education was not found to modify the focal relationship for males or females. CONCLUSIONS: The findings suggest that the relationship between average alcohol volume consumed per day and suicide is nuanced. Additional research on the respective relationship is needed, including repeated measures of average alcohol consumption over time.

Feasibility and effectiveness of extended-release buprenorphine (XR-BUP) among correctional populations: a systematic review.

Background: Medications for opioid use disorder (MOUD) reduce risks for overdose among correctional populations. Among other barriers, daily dosing requirements hinder treatment continuity post-release. Extended-release buprenorphine (XR-BUP) may therefore be beneficial. However, limited evidence exists.Objectives: To conduct a systematic review examining the feasibility and effectiveness of XR-BUP among correctional populations.Methods: Searches were carried out in Pubmed, Embase, and PsychINFO in October 2023. Ten studies reporting on feasibility or effectiveness of XR-BUP were included, representing n = 819 total individuals (81.6% male). Data were extracted and narratively reported under the following main outcomes: 1) Feasibility; 2) Effectiveness; and 3) Barriers and Facilitators.Results: Studies were heterogeneous. Correctional populations were two times readier to try XR-BUP compared to non-correctional populations. XR-BUP was feasible and safe, with no diversion, overdoses, or deaths; several negative side effects were reported. Compared to other MOUD, XR-BUP significantly reduced drug use, resulted in similar or higher treatment retention rates, fewer re-incarcerations, and was cost-beneficial, with a lower overall monthly/yearly cost. Barriers to XR-BUP, such as side effects and a fear of needles, as well as facilitators, such as a lowered risk of opioid relapse, were also identified.Conclusion: XR-BUP appears to be a feasible and potentially effective alternative treatment option for correctional populations with OUD. XR-BUP may reduce community release-related risks, such as opioid use and overdose risk, as well as barriers to treatment retention. Efforts to expand access to and uptake of XR-BUP among correctional populations are warranted.

Impact of health spending on hospitalization rates in Baltic countries: a comparative analysis.

INTRODUCTION: This study examines the association between healthcare indicators and hospitalization rates in three high-income European countries, namely Estonia, Latvia, and Lithuania, from 2015 to 2020. METHOD: We used a sex-stratified generalized additive model (GAM) to investigate the impact of select healthcare indicators on hospitalization rates, adjusted by general economic status-i.e., gross domestic product (GDP) per capita. RESULTS: Our findings indicate a consistent decline in hospitalization rates over time for all three countries. The proportion of health expenditure spent on hospitals, the number of physicians and nurses, and hospital beds were not statistically significantly associated with hospitalization rates. However, changes in the number of employed medical doctors per 10,000 population were statistically significantly associated with changes of hospitalization rates in the same direction, with the effect being stronger for males. Additionally, higher GDP per capita was associated with increased hospitalization rates for both males and females in all three countries and in all models. CONCLUSIONS: The relationship between healthcare spending and declining hospitalization rates was not statistically significant, suggesting that the healthcare systems may be shifting towards primary care, outpatient care, and on prevention efforts.

A dose-response meta-analysis on the relationship between average amount of alcohol consumed and death by suicide.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 30g/day, and 1.71 (95% CI: 1.25, 2.33) and 11.75 (95% CI: 1.38, 100.33) for 50g/day, respectively. CONCLUSIONS: 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.

Examining inequities in access to opioid agonist treatment (OAT) take-home doses (THD): A Canadian OAT guideline synthesis and systematic review.

BACKGROUND: Daily supervised Opioid Agonist Treatment (OAT) medication has been identified as a barrier to treatment retention. Canadian OAT guidelines outline take-home dose (THD) criteria, yet, OAT prescribers use their clinical judgement to decide whether an individual is 'clinically stable' to receive THD. There is limited information regarding whether these decisions may result in inequitable access to THD, including in the context of updated COVID-19 guidance. The current Canadian OAT THD guideline synthesis and systematic review aimed to address this knowledge gap. METHODS: This systematic review included a two-pronged approach. First, we searched available academic literature in Embase, Medline, and PsychINFO up until October 12th, 2022, to identify studies that compared characteristics of individuals on OAT who had and had not been granted access to THD to explore potential inequities in access. Next, we identified all Canadian national and provincial OAT guidelines through a semi-structured grey literature search (conducted between September-October 2022) and extracted all THD 'stability' and allowances/timeline criteria to compare against characteristics identified in the literature search. Data from both review arms were synthesized and narratively presented. RESULTS: A total of n = 56 guidelines and n = 7 academic studies were included. The systematic review identified a number of patient characteristics such as age, sex, race/ethnicity, marital status, housing, employment, neighborhood income, drug use, mental health, health service utilization, as well as treatment duration that were associated with differential access to THD. The Canadian OAT THD guideline synthesis identified many of these same characteristics as 'stability' criteria, underscoring the potential for Canadian OAT guidelines to result in inequitable access to THD. CONCLUSIONS: This two-pronged literature review demonstrated that current guidelines likely contribute to inequitable OAT THD access due primarily to inconsistent 'stability' criteria across guidelines. More research is needed to understand differential OAT THD access with a focus on prescriber decision-making and evaluating associated treatment and safety outcomes. The development of a client-centered, equity-focused, and evidence-informed decision making framework that incorporates more clear definitions of 'stability' criteria and indications for prescriber discretion is warranted.

Sex-Specific Association of Alcohol Use Disorder With Suicide Mortality: A Systematic Review and Meta-Analysis.

Importance: Despite individual studies suggesting that sex differences exist in the association between alcohol use disorder (AUD) and suicide, most existing systematic reviews and meta-analyses have reported associations across the sexes. Objective: To estimate the sex-specific association between AUD and suicide mortality. Data Sources: Embase, MEDLINE (including MEDLINE In-Process), PsycINFO, PubMed, and Web of Science were searched from database inception to April 27, 2022. Study Selection: Inclusion criteria consisted of the following: (1) original, quantitative study, (2) inclusion of a measure of association and its corresponding measure of variability (or sufficient data to calculate these [eg, 95% CI]), and (3) results stratified by sex. Data Extraction and Synthesis: Data extraction was completed by one reviewer and then cross-checked by a second reviewer. Risk of bias was assessed by study design. Categorical random-effects meta-analyses were conducted to obtain sex-specific pooled estimates of the association between AUD and suicide mortality risk. Methodological moderators (ie, study design and comparator group) were assessed using sex-stratified meta-regressions. Main Outcomes and Measures: The association between AUD and suicide mortality. Results: A total of 16 347 unique records were identified in the systematic search; 24 studies were ultimately included for 37 870 699 participants (59.7% male and 40.3% female) (23 risk estimates for male and 17 for female participants). Participants ranged in age from 15 years to 65 years or older. Sex-specific meta-regression models indicated that study design (ie, longitudinal vs cross-sectional study design) affected the observed association between AUD and suicide mortality for both male participants (log odds ratio, 0.68 [95% CI, 0.08-1.28]; P = .03) and female participants (log odds ratio, 1.41 [95% CI, 0.57-2.24]; P < .001). For males and females, among longitudinal studies, the pooled odds ratios were 2.68 (95% CI, 1.86-3.87; I2 = 99% [n = 14]) and 2.39 (95% CI, 1.50-3.81; I2 = 90% [n = 11]), respectively. Conclusions and Relevance: This systematic review and meta-analysis yielded substantive evidence that AUD was associated with suicide mortality and that the association was similar across the sexes. The findings underscore the importance of identifying and treating AUD as part of a comprehensive suicide prevention strategy.

The use of machine learning on administrative and survey data to predict suicidal thoughts and behaviors: a systematic review.

Background: Machine learning is a promising tool in the area of suicide prevention due to its ability to combine the effects of multiple risk factors and complex interactions. The power of machine learning has led to an influx of studies on suicide prediction, as well as a few recent reviews. Our study distinguished between data sources and reported the most important predictors of suicide outcomes identified in the literature. Objective: Our study aimed to identify studies that applied machine learning techniques to administrative and survey data, summarize performance metrics reported in those studies, and enumerate the important risk factors of suicidal thoughts and behaviors identified. Methods: A systematic literature search of PubMed, Medline, Embase, PsycINFO, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Allied and Complementary Medicine Database (AMED) to identify all studies that have used machine learning to predict suicidal thoughts and behaviors using administrative and survey data was performed. The search was conducted for articles published between January 1, 2019 and May 11, 2022. In addition, all articles identified in three recently published systematic reviews (the last of which included studies up until January 1, 2019) were retained if they met our inclusion criteria. The predictive power of machine learning methods in predicting suicidal thoughts and behaviors was explored using box plots to summarize the distribution of the area under the receiver operating characteristic curve (AUC) values by machine learning method and suicide outcome (i.e., suicidal thoughts, suicide attempt, and death by suicide). Mean AUCs with 95% confidence intervals (CIs) were computed for each suicide outcome by study design, data source, total sample size, sample size of cases, and machine learning methods employed. The most important risk factors were listed. Results: The search strategy identified 2,200 unique records, of which 104 articles met the inclusion criteria. Machine learning algorithms achieved good prediction of suicidal thoughts and behaviors (i.e., an AUC between 0.80 and 0.89); however, their predictive power appears to differ across suicide outcomes. The boosting algorithms achieved good prediction of suicidal thoughts, death by suicide, and all suicide outcomes combined, while neural network algorithms achieved good prediction of suicide attempts. The risk factors for suicidal thoughts and behaviors differed depending on the data source and the population under study. Conclusion: The predictive utility of machine learning for suicidal thoughts and behaviors largely depends on the approach used. The findings of the current review should prove helpful in preparing future machine learning models using administrative and survey data. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022333454 identifier CRD42022333454.

The prevalence of alcohol-related deaths in autopsies performed in Lithuania between 2017 and 2020: a cross-sectional study.

BACKGROUND: Consumption of alcohol is a risk factor for non-communicable and infectious diseases, mental health problems, and can lead injuries and violence. The aim of this study was to evaluate the prevalence of alcohol-involved deaths among decedents who died of external causes and underwent autopsy in Lithuania. METHODS: Study includes age persons of any age (from 0 to 110 years) who died and were autopsied in Lithuania from 1 January 2017 to 31 December 2020. Data were obtained from the Lithuanian State Register of Deaths and Their Causes. RESULTS: Among external causes of death, the presence of alcohol was detected in 55.0% of cases. Male decedents had a significantly higher number of positive BAC level recorded, at 46.6%, compared with female decedents (32.1%; P < 0.001). The highest incidence of deaths where the alcohol was detected in the deceased's blood was found when the decedent was listed as being in the victims of assault group (71.5%, 95% CI 65.4-77.2). However, the highest median BAC score was found for those in the accidents group (59.7%, 95% CI: 58.2-61.2, BAC 2.42 ‰, IQR 1.86). CONCLUSIONS: The findings of this study suggest that alcohol use may be a contributing factor in a wide range of fatal incidents, including accidents, injuries, and cases of violent intent. Inequalities between males and females were identified, with a higher proportion of males with alcohol detected in blood at the time of death.

Trends of alcohol-attributable deaths in Lithuania 2001-2021: epidemiology and policy conclusions.

BACKGROUND: Lithuania, a Baltic country in the European Union, can be characterized by high alcohol consumption and attributable burden. The aim of this contribution is to estimate the mortality burden due to alcohol use for the past two decades based on different relative risk functions, identify trends, and analyse the associations of alcohol-attributable burden with alcohol control policies and life expectancy. METHODS: The standard methodology used by the World Health Organization for estimating alcohol-attributable mortality was employed to generate mortality rates for alcohol-attributable mortality, standardized for Lithuania's 2021 population distribution. Joinpoint analysis, T-tests, correlations, and regression analyses including meta-regressions were used to describe trends and associations. RESULTS: Age-standardized alcohol-attributable mortality was high in Lithuania during the two decades between 2001 and 2021, irrespective of which relative risks were used for the estimates. Overall, there was a downward trend, mainly in males, which was associated with four years of intensive implementation of alcohol control policies in 2008, 2009, 2017, and 2018. For the remaining years, the rates of alcohol-attributable mortality were stagnant. Among males, the correlations between alcohol-attributable mortality and life expectancy were 0.90 and 0.76 for Russian and global relative risks respectively, and regression analyses indicated a significant association between changes in alcohol-attributable mortality and life expectancy, after controlling for gross domestic product. CONCLUSIONS: Male mortality and life expectancy in Lithuania were closely linked to alcohol-attributable mortality and markedly associated with strong alcohol control policies. Further implementation of such policies is predicted to lead to further improvements in life expectancy.

Prototyping the implementation of a suicide prevention protocol in primary care settings using PDSA cycles: a mixed method study.

Introduction: In Canada, approximately 4,500 individuals die by suicide annually. Approximately 45% of suicide decedents had contact with their primary care provider within the month prior to their death. Current versus never smokers have an 81% increased risk of death by suicide. Those who smoke have additional risks for suicide such as depression, chronic pain, alcohol, and other substance use. They are more likely to experience adverse social determinants of health. Taken together, this suggests that smoking cessation programs in primary care could be facilitators of suicide prevention, but this has not been studied. Study objectives: The objectives of the study are to understand barriers/facilitators to implementing a suicide prevention protocol within a smoking cessation program (STOP program), which is deployed by an academic mental health and addiction treatment hospital in primary care clinics and to develop and test implementation strategies to facilitate the uptake of suicide screening and assessment in primary care clinics across Ontario. Methods: The study employed a three-phase sequential mixed-method design. Phase 1: Conducted interviews guided by the Consolidated Framework for Implementation Research exploring barriers to implementing a suicide prevention protocol. Phase 2: Performed consensus discussions to map barriers to implementation strategies using the Expert Recommendations for Implementing Change tool and rank barriers by relevance. Phase 3: Evaluated the feasibility and acceptability of implementation strategies using Plan Do Study Act cycles. Results: Eleven healthcare providers and four research assistants identified lack of training and the need of better educational materials as implementation barriers. Participants endorsed and tested the top three ranked implementation strategies, namely, a webinar, adding a preamble before depression survey questions, and an infographic. After participating in the webinar and reviewing the educational materials, all participants endorsed the three strategies as acceptable/very acceptable and feasible/very feasible. Conclusion: Although there are barriers to implementing a suicide prevention protocol within primary care, it is possible to overcome them with strategies deemed both acceptable and feasible. These results offer promising practice solutions to implement a suicide prevention protocol in smoking cessation programs delivered in primary care settings. Future efforts should track implementation of these strategies and measure outcomes, including provider confidence, self-efficacy, and knowledge, and patient outcomes.

Evaluation of the risk relationship between average alcohol volume consumed and suicide: An analysis of mortality linked cohort data.

Objective: To evaluate the relationship between average alcohol volume consumed per day and suicide. Methods: Data from the annual, cross-sectional US National Health Interview Survey, 1997-2018, was obtained, and linked to the 2019 National Death Index. The association between average alcohol volume consumed in grams per day (g/day) and suicide was quantified using Cox proportional hazards model (multiplicative) and Aalen's additive hazard model. All analyses were stratified by sex, and adjusted for education, marital status, race/ethnicity, and survey year. Results: On the multiplicative scale, for males, former drinkers and those who consumed on average (40, 60] g/day had about 53% (HR=1.53, 95% CI: 1.10, 2.13) and 77% (HR=1.77, 95% CI: 1.17, 2.66) greater risk of dying by suicide, compared to lifetime abstainers, respectively. There was no significant association found for former or current drinkers among females, on the multiplicative scale. On the additive scale, for males and females, being a former drinker was associated with 11.4 (95% CI: 2.3, 20.4) and 5.6 (95% CI: 0.8, 10.4) additional deaths per 100,000 person years, compared to lifetime abstainers. For males only, drinking (40, 60] g/day on average was associated with 23.2 (95% CI: 6.7, 39.7) additional deaths per 100,000 person years. Level of education was not found to modify the focal relationship for males or females. Conclusions: The findings suggest that the relationship between average alcohol volume consumed per day and suicide is nuanced. Additional research on the respective relationship is needed, including repeated measures of average alcohol consumption over time.

Impact of the WHO "best buys" for alcohol policy on consumption and health in the Baltic countries and Poland 2000-2020.

Alcohol use is a major risk factor for burden of disease. This narrative review aims to document the effects of major alcohol control policies, in particular taxation increases and availability restrictions in the three Baltic countries (Estonia, Latvia, and Lithuania) between 2000 and 2020. These measures have been successful in curbing alcohol sales, in general without increasing consumption of alcoholic beverages from unrecorded sources; although for more recent changes this may have been partly due to the COVID-19 pandemic. Moreover, findings from time-series analyses suggest improved health, measured as reductions in all-cause and alcohol-attributable mortality, as well as narrowing absolute mortality inequalities between lower and higher educated groups. For most outcomes, there were sex differences observed, with alcohol control policies more strongly affecting males. In contrast to this successful path, alcohol control policies were mostly dismantled in the neighbouring country of Poland, resulting in a rising death toll due to liver cirrhosis and other alcohol-attributable deaths. The natural experiment in this region of high-income European countries with high consumption levels highlights the importance of effective alcohol control policies for improving population health.

Alcohol-attributable mortality and alcohol control policy in the Baltic Countries and Poland in 2001-2020: an interrupted time-series analysis.

BACKGROUND: The Baltic countries-Lithuania, Latvia and Estonia-are characterized by a high rate of fully alcohol-attributable mortality, compared with Poland. Alcohol control policy measures implemented since 2001 in the Baltic countries included a restriction on availability and an increase in excise taxation, among others. The aim of the current study was to evaluate the relationship between alcohol control policy implementation and alcohol-attributable mortality in the Baltic countries and Poland. METHODS: Alcohol-attributable mortality data for 2001-2020 was defined by codes 100% alcohol-attributable for persons aged 15 years and older in the Baltic countries and Poland. Alcohol control policies implemented between 2001 and 2020 were identified, and their impact on alcohol-attributable mortality was evaluated using an interrupted time-series methodology by employing a generalized additive model. RESULTS: Alcohol-attributable mortality was significantly higher in the Baltic countries, compared with Poland, for both males and females. In the final reduced model, alcohol control policy significantly reduced male alcohol-attributable mortality by 7.60% in the 12 months post-policy implementation. For females, the alcohol control policy mean-shift effect was higher, resulting in a significant reduction of alcohol-attributable mortality by 10.77% in the 12 months post-policy implementation. The interaction effects of countries and policy tested in the full model were not statistically significant, which indicated that the impact of alcohol control policy on alcohol-attributable mortality did not differ across countries for both males and females. CONCLUSIONS: Based on the findings of the current study, alcohol control policy in the form of reduced availability and increased taxation was associated with a reduction in alcohol-attributable mortality among both males and females.

Modular chimeric cytokine receptors with leucine zippers enhance the antitumour activity of CAR T cells via JAK/STAT signalling.

The limited availability of cytokines in solid tumours hinders maintenance of the antitumour activity of chimeric antigen receptor (CAR) T cells. Cytokine receptor signalling pathways in CAR T cells can be activated by transgenic expression or injection of cytokines in the tumour, or by engineering the activation of cognate cytokine receptors. However, these strategies are constrained by toxicity arising from the activation of bystander cells, by the suboptimal biodistribution of the cytokines and by downregulation of the cognate receptor. Here we show that replacement of the extracellular domains of heterodimeric cytokine receptors in T cells with two leucine zipper motifs provides optimal Janus kinase/signal transducer and activator of transcription signalling. Such chimeric cytokine receptors, which can be generated for common γ-chain receptors, interleukin-10 and -12 receptors, enabled T cells to survive cytokine starvation without induction of autonomous cell growth, and augmented the effector function of CAR T cells in vitro in the setting of chronic antigen exposure and in human tumour xenografts in mice. As a modular design, leucine zippers can be used to generate constitutively active cytokine receptors in effector immune cells.