Beta-adrenergic glaucoma drugs reduce lymphatic clearance from the eye: A sequential photoacoustic imaging study.

Our study aims to determine whether the beta-adrenergic system is involved in the regulation of lymphatic drainage from the eye. For this purpose, we assessed the effect of 2 topical beta-adrenergic blockers, timolol and betaxolol, commonly used as glaucoma drugs, on lymphatic clearance of albumin from the aqueous humor to neck lymph nodes. Adult mice were treated with either topical timolol, a non-selective ß-blocker, 0.5% (n = 8), or topical betaxolol, a selective ß1-adrenergic blocker, 0.5% (n = 6) twice daily for 14 days and compared to respective control groups (n = 5 and n = 7). Changes in lymphatic clearance from the eye were assessed using a quantitative in vivo photoacoustic imaging approach. In all subjects, right eye and neck lymph nodes were longitudinally assessed by sequential photoacoustic imaging just prior to near-infrared dye injection into the anterior chamber of the eye, and 20 min, 2 and 4 h after injection. Repeat measurements of mean pixel intensities (MPIs) of right eyes and nodes were performed at all timepoints. The areas under the curves (AUC) were calculated and the AUC of the treated-group was compared to that of controls using the Mann-Whitney U test. The slopes of MPI of each region of interest over time were compared using the linear mixed model after adjusting for IOP decrease after treatment and other parameters such as sex and body weight. In the timolol-treated group, right neck nodes showed significant decrease in AUC signal intensity compared with controls (P = 0.003), and significant decrease in slope of MPI compared with controls (P = 0.0025). In the betaxolol-treated group, right neck nodes showed significant decrease in AUC signal intensity compared with controls (P = 0.02), and significant decrease in slope of MPI compared with controls (P = 0.0069). Topical treatment with timolol and betaxolol reduced lymphatic clearance of albumin from the aqueous humor to the neck lymph nodes. This finding may be relevant for the management of secondary glaucomas and inflammatory eye disease in which the clearance of accumulated proteins and antigen from the eye is important to disease recovery and sight protection. This study suggests that the beta-adrenergic system plays a role in the regulation of lymphatic clearance from the eye.

A novel photoacoustic-fluorescent contrast agent for quantitative imaging of lymphatic drainage.

In vivo near-infrared (NIR) photoacoustic imaging (PAI) studies using novel contrast agents require validation, often via fluorescence imaging. Bioconjugation of NIR dyes to proteins is a versatile platform to obtain contrast agents for specific biomedical applications. Nonfluorescent NIR dyes with higher photostability present advantages for quantitative PAI, compared to most fluorescent NIR dyes. However, they don't provide a fluorescence signal required for fluorescence imaging. Here, we designed a hybrid PA-fluorescent contrast agent by conjugating albumin with a NIR nonfluorescent dye (QC-1) and a visible spectrum fluorescent dye, a BODIPY derivative. The new hybrid tracer QC-1/BSA/BODIPY (QBB) had a low minimum detectable concentration (2.5µM), a steep linear range (2.4-54.4 µM; slope 3.39 E -5), and high photostability. Tracer signal was measured in vivo using PAI to quantify its drainage from eye to the neck and its localization in the neck lymph node was validated with postmortem fluorescence imaging.

Retinal Spheroids and Axon Pathology Identified in Amyotrophic Lateral Sclerosis.

Purpose: To determine whether patients with amyotrophic lateral sclerosis (ALS) show retinal axon pathology. Methods: Postmortem eyes from 10 patients with ALS were sectioned and compared with 10 age-matched controls. Retinal sections were evaluated with periodic acid Schiff and phosphorylated (P-NF) and nonphosphorylated (NP-NF) forms of neurofilament with SMI 31 and 32 antibodies. Spheroids identified in the retinal nerve fiber layer were counted and their overall density was calculated in central, peripheral, and peripapillary regions. P-NF intensity was quantified. Morphometric features of ALS cases were compared with age-matched controls using the exact Wilcoxon matched-pairs signed-rank test. Results: Distinct periodic acid Schiff-positive round profiles were identified in the retinal nerve fiber layer of patients with ALS and were most commonly observed in the peripapillary and peripheral retina. The density of periodic acid Schiff-positive spheroids was significantly greater in patients with ALS compared with controls (P = 0.027), with increased density in the peripapillary region (P = 0.047). Spheroids positive for P-NF and NP-NF were detected. P-NF-positive spheroid density was significantly increased in patients with ALS (P = 0.004), while the density of NP-NF spheroids did not differ significantly between ALS and control groups (P > 0.05). P-NF immunoreactivity in the retinal nerve fiber layer was significantly greater in patients with ALS than in controls (P = 0.002). Conclusions: Retinal spheroids and axon pathology discovered in patients with ALS, similar to hallmark findings in spinal cord motor neurons, point to disrupted axon transport as a shared pathogenesis. Retinal manifestations detected in ALS suggest a novel biomarker detectable by noninvasive retinal imaging to help to diagnose and monitor ALS disease.

Vulnerable road-user deaths in Brazil: a Bayesian hierarchical model for spatial-temporal analysis.

Reducing the road traffic injuries burden is relevant to many sustainable development goals (SDG), in particular SDG3 - to establish good health and well-being. To describe the spatial-temporal trends and identify hotspot regions for fatal road traffic injuries, a Bayesian hierarchical Poisson model was used to analyze data on vulnerable road users (bicyclist, motorcyclist and pedestrians) in Brazil from 1999 to 2016. During the study period, mortality rates for bicyclists remained almost unchanged (0.6 per 100,000 people) but rose dramatically for motorcyclists (from 1.0 in 1999 to 6.0 per 100,000 people in 2016) and decreased for pedestrians (from 6.3 to 3.0 per 100,000 people). Spatial analyses accounting for socio-economic factors showed that the central and northeastern microregions of Brazil are hotspot areas for fatal injuries among motorcyclists while the southern areas are for pedestrians.

Age-related decline of lymphatic drainage from the eye: A noninvasive in vivo photoacoustic tomography study.

We aim to determine whether lymphatic drainage from the eye changes with age. Using quantitative photoacoustic tomography, groups of young and older mice were studied in the live state. 10 CD-1 mice of 2-3 months (5M/5F) were studied in addition to 13 older mice of 12-13 months (6M/7F). In each of 23 mice, near-infrared tracer (a near-infrared dye, QC-1 conjugated with Bovine Serum Albumin) was injected into the right eye, and imaging of ipsilateral cervical lymph nodes was performed with laser pulses at 11 different wavelengths prior to and 20 min, 2, 4 and 6 h after injection. Mean pixel intensities (MPIs) of nodes were calculated at each imaging session. The areas under the curves (AUC) were calculated for both groups of mice and compared using the t-test. The slopes of MPI of each region of interest were compared using the linear mixed model before and after adjusting for sex, body weight and intraocular pressure of the right eye. The mean intraocular pressure of right eyes before injection was similar in older and younger groups (12.77 ± 2.01 mmHg and 12.90 ± 2.38 mmHg, respectively; p = 0.888). In each mouse, the photoacoustic signal was detected in the right cervical lymph nodes at the 2-h time point following tracer injection into the right eye. At the 4 and 6 h imaging times, a steady increase of tracer signal was observed. Areas under the curve in the right cervical nodes were decreased significantly in older mice compared to younger mice (p = 0.007). The slopes of MPI in the nodes were significantly decreased in old mice compared to young mice both before and after adjusting for sex, body weight and intraocular pressure of the right eye (p = 0.003). In conclusion, lymphatic drainage from the eye is significantly reduced in older eyes. This finding suggests that impaired lymphatic clearance of aqueous humor, proteins and antigens from the eye may contribute to age-related disease of the eye such as glaucoma and inflammatory eye disease.

Geospatial, racial, and educational variation in firearm mortality in the USA, Mexico, Brazil, and Colombia, 1990-2015: a comparative analysis of vital statistics data.

BACKGROUND: Firearm mortality is a leading, and largely avoidable, cause of death in the USA, Mexico, Brazil, and Colombia. We aimed to assess the changes over time and demographic determinants of firearm deaths in these four countries between 1990 and 2015. METHODS: In this comparative analysis of firearm mortality, we examined national vital statistics data from 1990-2015 from four publicly available data repositories in the USA, Mexico, Brazil, and Colombia. We extracted medically-certified deaths and underlying population denominators to calculate the age-specific and sex-specific firearm deaths and the risk of firearm mortality at the national and subnational level, by education for all four countries, and by race or ethnicity for the USA and Brazil. Analyses were stratified by intent (homicide, suicide, unintentional, or undetermined). We quantified avoidable mortality for each country using the lowest number of subnational age-specific and period-specific death rates. FINDINGS: Between 1990 and 2015, 106·3 million medically-certified deaths were recorded, including 2 472 000 firearm deaths, of which 851 000 occurred in the USA, 272 000 in Mexico, 855 000 in Brazil, and 494 000 in Colombia. Homicides accounted for most of the firearm deaths in Mexico (225 000 [82·7%]), Colombia (463 000 [93·8%]), and Brazil (766 000 [89·5%]). Suicide accounted for more than half of all firearm deaths in the USA (479 000 [56·3%]). In each country, firearm mortality was highest among men aged 15-34 years, accounting for up to half of the total risk of death in that age group. During the study period, firearm mortality risks increased in Mexico and Brazil but decreased in the USA and Colombia, with marked national and subnational geographical variation. Young men with low educational attainment were at increased risk of firearm homicide in all four countries, and in the USA and Brazil, black and brown men, respectively, were at the highest risk. The risk of firearm homicide was 14 times higher in black men in the USA aged 25-34 years with low educational attainment than comparably-educated white men (1·52% [99% CI 1·50-1·54] vs 0·11% [0·10-0·12]), and up to four times higher than in comparably-educated men in Brazil, Colombia, and Mexico. In the USA, the risk of firearm homicide was more than 30 times higher in black men with post-secondary education than comparably educated white men. If countries could achieve the same firearm mortality rates nationally as in their lowest-burden states, 1 777 800 firearm deaths at all ages and in both sexes could be avoided, including 1 028 000 deaths in men aged 15-34 years. INTERPRETATION: Firearm mortality in the USA, Mexico, Brazil, and Colombia is highest among young adult men, and is strongly associated with race and ethnicity, and low education levels. Reductions in firearm deaths would improve life expectancy, particularly for black men in the USA, and would reduce racial and educational disparities in mortality. FUNDING: Canadian Institutes of Health Research and the University of Toronto Connaught Global Challenge.

Divergence and convergence in cause-specific premature adult mortality in Mexico and US Mexican Hispanics from 1995 to 2015: analyses of 4.9 million individual deaths.

Background: Mexicans and US Mexican Hispanics share modifiable determinants of premature mortality. We compared trends in mortality at ages 30-69 in Mexico and among US Mexican Hispanics from 1995 to 2015. Methods: We examined nationally representative statistics on 4.2 million Mexican and 0.7 million US deaths to examine cause-specific mortality. We used lung cancer indexed methods to estimate smoking-attributable deaths stratified by high and lower burden Mexican states. Results: In 1995-99, Mexican men had about 30% higher relative risk of death from all causes than US Mexican Hispanic men, and this difference nearly doubled to 58% by 2010-15. The divergence between Mexican and US Mexican Hispanic women over this time period was less marked. Among US Mexican Hispanics, declines in the risk of smoking-attributable death constituted about 25-30% of the declines in the overall risk of death. However, among Mexican men the declines in the risk of smoking-attributable deaths were offset by increases in causes of death not due to smoking. Homicide rates (mostly from guns) rose among men in Mexico from 2005 to 2010, but not among Mexican women or US Mexican Hispanic men or women. The probability at 30-69 years of death from cardiac disease diverged significantly between Mexicans and US Mexican Hispanics, reaching 10% and 5% for men, and 7% and 2% for women, respectively. Conclusions: Large differences in premature mortality between otherwise genetically and culturally similar groups arise from a few modifiable factors, most notably smoking, untreated diabetes and homicide.

Smoking and binge-drinking among adolescents, Ontario, Canada: Does the school neighbourhood matter?

This study examines whether access to alcohol and tobacco around the school relates to higher or lower odds of cigarette smoking and binge-drinking among Ontario high school students. The 2013 Ontario Student Drug Use and Health Survey provides data on self-reported smoking and drinking, individual covariates and subjective socio-economic status for 6142 students (grades 9-12) in Ontario, Canada. Locations of schools were geocoded and 1.6km network buffers defined the school neighbourhoods. Multi-level logistic regression examines individual and school neighbourhood factors with smoking and binge drinking as the dependent variable. Higher density of retail outlets increased the odds of smoking, but not the odds of binge-drinking. Older age, lower SES and being male increased the odds of smoking; while older age and being male also increased the odds of binge-drinking. Lower SES and higher population density decreased the odds of binge-drinking. Proximity to tobacco and alcohol outlets was not significant. Findings showed that a greater number of outlets in the school neighbourhood is significantly associated with higher odds of smoking, but not binge-drinking. School neighbourhood access to tobacco outlets should be considered when formulating policy interventions to reduce smoking for adolescents.

Looking beyond cigarettes: Are Ontario adolescents with asthma less likely to smoke e-cigarettes, marijuana, waterpipes or tobacco cigarettes?

OBJECTIVES: The purpose of this paper is to examine whether high school students in Ontario with asthma smoke cigarettes, waterpipes, marijuana or e-cigarettes more or less than those without asthma. METHODS: The 2013 Ontario Student Drug Use and Health Survey provides self-report data on tobacco cigarettes, waterpipes, marijuana and e-cigarette smoking and asthma rates from 109 high schools in Ontario, Canada. Individual and social characteristics were also collected. Multiple binary logistic regression models measures the association with the various types of smoking in relation to asthma. RESULTS: Adolescents with asthma have higher odds of smoking e-cigarettes or smoking any type including either cigarettes, waterpipes, marijuana or e-cigarettes. Respondents of lower socio-economic status had a higher odds of smoking marijuana or any type. Boys were more likely to smoke waterpipes, e-cigarettes or any type, while students in higher grades had a higher odds of smoking cigarettes, waterpipes, marijuana or any type. CONCLUSIONS: Results from this study suggest that adolescents with asthma have a higher odds of smoking e-cigarettes than those without asthma, but no relationship was found for cigarettes, waterpipes or marijuana. Findings present some new challenges as technology changes how adolescents can smoke. Public health campaigns should target adolescents, especially those with asthma, to raise their awareness of the risks of all types of smoking including e-cigarettes.

The search for healthy schools: A multilevel latent class analysis of schools and their students.

The objective of this study was to establish and investigate a taxonomy of school health among high school students in Ontario, Canada. Data analyzed were based on 3358 9th-12th graders attending 103 high schools who participated in the 2011 Ontario Student Drug Use and Health Survey. Based on 10 health-related indicators, multilevel latent class analysis was used to extract 4 student-level latent classes and 3 school-level latent classes. Unhealthy schools (19% of schools) had the lowest proportion of healthy students (39%) and the highest proportion of substance-using (31%) and unhealthy (18%) students. Healthy schools (66%) contained the highest proportion of healthy students (56%) and smaller proportions of substance-using (22%) and unhealthy students (8%). Distressed schools (15%) were similar to healthy schools in terms of the proportions of healthy and unhealthy students. Distressed schools, however, were characterized by having the largest proportion of distressed students (35%) and the lowest proportion of substance-using students (4%). Meaningful categories of schools with respect to healthy environments can be identified and these categories could be used for focusing interventions and evaluating school health programs.

Ten-year trends in overweight/obesity among Ontario middle and high school students and their use in establishing baseline measures for government reduction targets.

OBJECTIVES: Public health concern about increasing levels of child/youth overweight and obesity has resulted in initiatives to address this issue. In 2012, the Ontario Ministry of Health and Long-Term Care (MOHLTC) established a target to reduce childhood obesity by 20% within five years. In this paper, we examine trends and establish baseline levels of overweight/obesity to assess the impacts of population-level interventions. METHODS: We analyzed 10 years (2003-2013) of data accumulated from six cycles of the Ontario Student Drug Use and Health Survey using logistic regression to assess trends in the prevalence of overweight/obesity among middle and high school students. The 2013 data are used to begin monitoring progress toward achieving the MOHLTC target. RESULTS: From 2003 through 2013, the prevalence of overweight/obesity among middle school students in the province remained stable overall and among all subgroups except 7th-grade females, who showed a significant linear decline. Among high school students, the prevalence of overweight/obesity showed a significant linear increase and an increase among 11th graders, females, and 10th- and 11th-grade females specifically. The prevalence remained stable but elevated among 9th- and 12th-grade females as well as among males in all grades. In 2013 (baseline for the MOHLTC target), 25.1% of students in grades 7-12 were overweight or obese, implying a presumed 2018 target of 20.1%. CONCLUSION: Ten-year trends in overweight/obesity indicate stability among males and significant linear increases in some female subgroups. Also, baseline data (2013) will facilitate the monitoring of future interventions aimed at achieving the 2018 MOHLTC target.

Differential predictors of ART adherence among HIV-monoinfected versus HIV/HCV-coinfected individuals.

Although adherence is an important key to the efficacy of antiretroviral therapy (ART), many people living with HIV (PLWH) fail to maintain optimal levels of ART adherence over time. PLWH with the added burden of Hepatitis C virus (HCV) coinfection possess unique challenges that potentially impact their motivation and ability to adhere to ART. The present investigation sought to (1) compare ART adherence levels among a sample of HIV/HCV-coinfected versus HIV-monoinfected patients, and (2) identify whether ART-related clinical and psychosocial correlates differ by HCV status. PLWH receiving ART (N = 215: 105 HIV/HCV-coinfected, 110 HIV-monoinfected) completed a comprehensive survey assessing ART adherence and its potential correlates. Medical chart extraction identified clinical factors, including liver enzymes. Results demonstrated that ART adherence did not differ by HCV status, with 83.7% of coinfected patients and 82.4% of monoinfected patients reporting optimal (i.e., ≥95%) adherence during a four-day recall period (p = .809). Multivariable logistic regression demonstrated that regardless of HCV status, optimal ART adherence was associated with experiencing fewer adherence-related behavioral skills barriers (AOR = 0.56; 95%CI = 0.43-0.73), lower likelihood of problematic drinking (AOR = 0.15; 95%CI = 0.04-0.67), and lower likelihood of methamphetamine use (AOR = 0.14; 95%CI = 0.03-0.69). However, among HIV/HCV-coinfected patients, optimal adherence was additionally associated with experiencing fewer ART adherence-related motivational barriers (AOR = 0.23; 95%CI = 0.08-0.62) and lower likelihood of depression (AOR = 0.06; 95%CI = 0.00-0.84). Findings suggest that although HIV/HCV-coinfected patients may face additional, distinct barriers to ART adherence, levels of adherence commensurate with those demonstrated by HIV-monoinfected patients might be achievable if these barriers are addressed.

Multiple health-risk behaviour and psychological distress in adolescence.

OBJECTIVE: To examine the prevalence and correlates of psychological distress in a school-based sample of Canadian adolescents. METHOD: Self-reported data of demographics, weight status, physical activity, screen-time, diet, substance use, and psychological distress were derived from a representative sample of 2935 students in grades 9 to 12 (M(age) = 15.9 years) from the 2009 Ontario Student Drug Use and Health Survey. RESULTS: Overall prevalence of psychological distress was 35.1%. Significant associations were shown between psychological distress and the following: being female, tobacco use, not meeting physical activity and screen-time recommendations, and inadequate consumption of breakfast and vegetables. CONCLUSIONS: These findings highlight the need for targeting greater physical health promotion for adolescents at risk of mental health problems.

Social relationships as a major determinant in the valuation of health states.

PURPOSE: To empirically determine the impact of the capacity to sustain social relationships on valuing health states. METHODS: 68 clinical experts conducted a health state valuation exercise in five sites using pairwise comparison, ranking, and person trade-off as elicitation methods. 23,840 pairwise comparisons of a total of 379 health states were analyzed by conditional logistic regression. RESULTS: Social relationships had a clear monotonic association with perceived disability: the more limited the capacity to sustain social relationships, the more disabling the resulting health state valuations. The highest level of limitations with respect to social relationships was associated with slightly lower impact on health state valuations compared to the highest level of limitations in physical functioning. CONCLUSIONS: Social relationships showed an independent contribution to health state valuations and should be included in health state measures.

Mode shifting in school travel mode: examining the prevalence and correlates of active school transport in Ontario, Canada.

BACKGROUND: Studies examining the correlates of school transport commonly fail to make the distinction between morning and afternoon school trips. The purpose of this study was to examine the prevalence and correlates of mode shift from passive in the morning to active in the afternoon among elementary and secondary school students in Ontario, Canada. METHODS: Data were derived from the 2009 cycle of the Ontario Student Drug Use and Health Survey (OSDUHS). 3,633 students in grades 7 through 12 completed self-administered questionnaires. Socio-demographic, behavioural, psychological, and environmental predictors of active school transport (AST) were assessed using logistic regression. RESULTS: Overall, 47% and 38% of elementary school students reported AST to and from school, respectively. The corresponding figures were 23% and 32% for secondary school students. The prevalence of AST varied temporarily and spatially. There was a higher prevalence of walking/biking found for elementary school students than for secondary school students, and there was an approximate 10% increase in AST in the afternoon. Different correlates of active school transport were also found across elementary and secondary school students. For all ages, students living in urban areas, with a shorter travel time between home and school, and having some input to the decision making process, were more likely to walk to and from school. CONCLUSIONS: Future research examining AST should continue to make the analytic distinction between the morning and afternoon trip, and control for the moderating effect of age and geography in predicting mode choice. In terms of practice, these variations highlight the need for school-specific travel plans rather than 'one size fits all' interventions in promoting active school transport.

Trajectory classes of decline in health-related quality of life in Parkinson's disease: a pilot study.

OBJECTIVE: To analyze the change in health-related quality-of-life (HRQoL) in patients with Parkinson's disease (PD) and to identify different classes of HRQoL decline. METHODS: A longitudinal cohort study was performed to assess clinical parameters (unified PD rating scale, Beck Depression Inventory) and HRQoL data (EuroQol, Parkinson's Disease Questionnaire [PDQ]-39) at baseline, 3, 6, 12, 24, and 36 months. A total of 145 patients with PD were consecutively recruited in the county of Northern Hessia, Germany, between January and June 2000. A latent growth mixture model was applied to analyse the heterogeneity in HRQoL trajectories. RESULTS: We successfully applied latent mixture growth modeling in order to identify different classes of HRQoL trajectories in PD. Three growth models were developed and each resulted in a four-class model of distinct patterns using the generic EuroQol instruments' outcomes (EuroQol-5 Dimensions and visual analogue scale) and the disease-specific PDQ-39. The four classes were defined by individual trajectory characteristics. Classes one and two represented trajectories with moderate declines over 36 months, but with different initial intercepts. Class three consisted mainly of patients who passed away during the observation period and therefore had a large HRQoL decline. Class four was characterized by a low level of HRQoL at baseline and a significant subsequent decline. CONCLUSIONS: The findings provide a more elaborate understanding of the variability in HRQoL reduction in PD over time. The classification of different HRQoL subgroups may help to explain the response of PD patients to the natural history of the disease. Future research will enable the identification of HRQoL responder subgroups on different treatment regimens.

An exploratory approach to analyzing alcohol control policy opinions held by Ontario adults.

Telephone interview data from a representative sample of 1,216 Ontario adults were analyzed using latent class analysis to determine whether distinct and homogeneous classes of individuals could be identified based on their responding patterns to 11 alcohol policy items. Five latent classes were identified and labeled as: dedicated liberalizers, moderate liberalizers, moderate controllers, dedicated controllers, and an ambivalent class. Multinomial regression analysis indicated that demographic and alcohol factors differentiated the classes. Those most opposed to alcohol controls, dedicated liberalizers, were more likely to be male, younger and heavier drinkers. Given their young age it is possible that further erosion of public support for alcohol controls may be expected.

Alcohol as a risk factor for liver cirrhosis: a systematic review and meta-analysis.

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.

Alcohol consumption and the risk of morbidity and mortality for different stroke types--a systematic review and meta-analysis.

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.

Typologies of cannabis users and associated characteristics relevant for public health: a latent class analysis of data from a nationally representative Canadian adult survey.

Cannabis is the most prevalently used illicit drug in Canada. Current policy consists primarily of universal use prohibition rather than interventions targeting specific risks and harms relevant for public health. This study aimed to identify distinct groups of cannabis users based on defined use characteristics in the Canadian population, and examine the emerging groups' associations with differential risk and harm outcomes. One thousand three hundred and three current (i.e. use in the past three months) cannabis users, based on data from the representative cross-sectional 2004 Canadian Addiction Survey (N = 13,909), were statistically assessed by a 'latent class analysis' (LCA). Emerging classes were examined for differential associations with socio-demographic, health and behavioral indicators on the basis of chi-square and analysis of variance techniques. Four distinct classes based on use patterns were identified. The class featuring earliest onset and highest frequency of use [22% of cannabis user sample or 2.2% (95% confidence interval (CI) = 1.8-2.7%) of the Canadian adult population] was disproportionately linked to key harms, including other illicit drug use, health problems, cannabis use and driving, and cannabis use problems. A public health framework for cannabis use is needed in Canada, meaningfully targeting effective interventions towards the minority of users experiencing elevated levels of risks and harms.