Efficacy and adverse events of oral isotretinoin for acne: a systematic review.

Despite many years of clinical use of isotretinoin, a comprehensive review of evidence for isotretinoin therapy in patients with acne is lacking. We searched MEDLINE, Embase, Cochrane Central, relevant web pages and bibliographies for randomized controlled trials in acne evaluating isotretinoin vs. control (placebo or other therapy). Data were extracted and summarized descriptively. Eleven trials were identified (total 760 patients randomized), containing mostly men. Mean treatment ages ranged from 18 to 47·9 years and participants generally had moderate-to-severe acne. Across all trials, isotretinoin therapy reduced acne lesion counts by a clinically relevant amount, and always by a greater amount than control, which was either placebo (two studies), oral antibiotics (seven studies) or other control (two studies). Across trials with an overall low risk of bias, two of three demonstrated statistically significant differences between isotretinoin and control. The frequency of adverse events was twice as high with isotretinoin (751 events) than with control (388 events). More than half of all adverse events were dermatological and related to dryness. Adverse events from isotretinoin causing participant withdrawal from trials (12 patients) included Stevens-Johnson syndrome, cheilitis, xerosis, acne flare, photophobia, elevated liver enzymes, decreased appetite, headaches and depressed mood. This review suggests that isotretinoin is effective in reducing acne lesion counts, but adverse events are common. This study was registered with PROSPERO number CRD42015025080.

Patterns of association of chronic medical conditions and major depression.

AIMS: Age and sex-related patterns of association between medical conditions and major depressive episodes (MDE) are important for understanding disease burden, anticipating clinical needs and for formulating etiological hypotheses. General population estimates are especially valuable because they are not distorted by help-seeking behaviours. However, even large population surveys often deliver inadequate precision to adequately describe such patterns. In this study, data from a set of national surveys were pooled to increase precision, supporting more precise characterisation of these associations. METHODS: The data were from a series of Canadian national surveys. These surveys used comparable sampling strategies and assessment methods for MDE. Chronic medical conditions were assessed using items asking about professionally diagnosed medical conditions. Individual-level meta-analysis methods were used to generate unadjusted, stratified and adjusted prevalence odds ratios for 11 chronic medical conditions. Random effects models were used in the meta-analysis. A procedure incorporating rescaled replicate bootstrap weights was used to produce 95% confidence intervals. RESULTS: Overall, conditions characterised by pain and inflammation tended to show stronger associations with MDE. The meta-analysis uncovered two previously undescribed patterns of association. Effect modification by age was observed in varying degrees for most conditions. This effect was most prominent for high blood pressure and cancer. Stronger associations were found in younger age categories. Migraine was an exception: the strength of association increased with age, especially in men. Second, especially for conditions predominantly affecting older age groups (arthritis, diabetes, back pain, cataracts, effects of stroke and heart disease) confounding by age was evident. For each condition, age adjustment resulted in strengthening of the associations. In addition to migraine, two conditions displayed distinctive patterns of association. Age adjusted odds ratios for thyroid disease reflected a weak association that was only significant in women. In epilepsy, a similar strength of association was found irrespective of age or sex. CONCLUSIONS: The prevalence of MDE is elevated in association with most chronic conditions, but especially those characterised by inflammation and pain. Effect modification by age may reflect greater challenges or difficulties encountered by young people attempting to cope with these conditions. This pattern, however, does not apply to migraine or epilepsy. Neurobiological changes associated with these conditions may offset coping-related effects, such that the association does not weaken with age. Prominent confounding by age for several conditions suggests that age adjustments are necessary in order to avoid underestimating the strength of these associations.

Seasonal variation in major depressive episode prevalence in Canada.

BACKGROUND: The purpose of this paper is to describe variation, over the months of the year, in major depressive episode (MDE) prevalence. This is an important aspect of the epidemiological description of MDE, and one that has received surprisingly little attention in the literature. Evidence of seasonal variation in MDE prevalence has been weak and contradictory. Most studies have sought to estimate the prevalence of seasonal affective disorder using cut-points applied to scales assessing mood seasonality rather than MDE. This approach does not align with modern classification in which seasonal depression is a diagnostic subtype of major depression rather than a distinct category. Also, some studies may have lacked power to detect seasonal differences. We addressed these limitations by examining the month-specific occurrence of conventionally defined MDE and by pooling data from large epidemiological surveys to enhance precision in the analysis. METHOD: Data from two national survey programmes (the National Population Health Survey and the Canadian Community Health Survey) were used, providing ten datasets collected between 1996 and 2013, together including over 500,000. These studies assessed MDE using a short form version of the Composite International Diagnostic Interview (CIDI) for major depression, with one exception being a 2012 survey that used a non-abbreviated version of the CIDI. The proportion of episodes occurring in each month was evaluated using items from the diagnostic modules and statistical methods addressing complex design features of these trials. Overall month-specific pooled estimates and associated confidence intervals were estimated using random effects meta-analysis and a gradient was assessed using a meta-regression model that included a quadratic term. RESULTS: There was considerable sampling variability when the month-specific proportions were estimated from individual survey datasets. However, across the various datasets, there was sufficient homogeneity to justify the pooling of these estimated proportions, producing large gains in precision. Seasonal variation was clearly evident in the pooled data. The highest proportion of episodes occurred in December, January and February and the lowest proportions occurred in June, July and August. The proportion of respondents reporting MDE in January was 70% higher than August, suggesting an association with implications for health policy. The pattern persisted with stratification for age group, sex and latitude. CONCLUSIONS: Seasonal effects in MDE may have been obscured by small sample sizes in prior studies. In Canada, MDE has clear seasonal variation, yet this is not addressed in the planning of services. These results suggest that availability of depression treatment should be higher in the winter than the summer months.

Childhood adversity and subsequent mental health status in adulthood: screening for associations using two linked surveys.

AIMS: Accumulating evidence links childhood adversity to negative health outcomes in adulthood. However, most of the available evidence is retrospective and subject to recall bias. Published reports have sometimes focused on specific childhood exposures (e.g. abuse) and/or specific outcomes (e.g. major depression). Other studies have linked childhood adversity to a large and diverse number of adult risk factors and health outcomes such as cardiovascular disease. To advance this literature, we undertook a broad examination of data from two linked surveys. The goal was to avoid retrospective distortion and to provide a descriptive overview of patterns of association. METHODS: A baseline interview for the Canadian National Longitudinal Study of Children and Youth collected information about childhood adversities affecting children aged 0-11 in 1994. The sampling procedures employed in a subsequent study called the National Population Health Survey (NPHS) made it possible to link n = 1977 of these respondents to follow-up data collected later when respondents were between the ages of 14 and 27. Outcomes included major depressive episodes (MDE), some risk factors and educational attainment. Cross-tabulations were used to examine these associations and adjusted estimates were made using the regression models. As the NPHS was a longitudinal study with multiple interviews, for most analyses generalized estimating equations (GEE) were used. As there were multiple exposures and outcomes, a statistical procedure to control the false discovery rate (Benjamini-Hochberg) was employed. RESULTS: Childhood adversities were consistently associated with a cluster of potentially related outcomes: MDE, psychotropic medication use and smoking. These outcomes may be related to one another since psychotropic medications are used in the treatment of major depression, and smoking is strongly associated with major depression. However, no consistent associations were observed for other outcomes examined: physical inactivity, excessive alcohol consumption, binge drinking or educational attainment. CONCLUSIONS: The conditions found to be the most strongly associated with childhood adversities were a cluster of outcomes that potentially share pathophysiological connections. Although prior literature has suggested that a very large number of adult outcomes, including physical inactivity and alcohol-related outcomes follow childhood adversity, this analysis suggests a degree of specificity with outcomes potentially related to depression. Some of the other reported adverse outcomes (e.g. those related to alcohol use, physical inactivity or more distal outcomes such as obesity and cardiovascular disease) may emerge later in life and in some cases may be secondary to depression, psychotropic medication use and smoking.

Retrospective and prospectively assessed childhood adversity in association with major depression, alcohol consumption and painful conditions.

BACKGROUND: Considerable evidence now links childhood adversity to a variety of adult health problems. Unfortunately, almost all of these studies have relied upon retrospective assessment of childhood events, creating a vulnerability to bias. In this study, we sought to examine three associations using data sources that allowed for both prospective and retrospective assessment of childhood events. METHODS: A 1994 national survey of children between the ages of 0 and 11 collected data from a 'person most knowledgeable' (usually the mother) about a child. It was possible to link data for n = 1977 of these respondents to data collected from the same people in a subsequent adult study. The latter survey included retrospective reports of childhood adversity. We examined three adult health outcomes in relation to prospectively and retrospectively assessed childhood adversity: major depressive episodes, excessive alcohol consumption and painful conditions. RESULTS: A strong association between childhood adversities (as assessed by both retrospective and prospective methods) and major depression was identified although the association with retrospective assessment was stronger. Weaker associations were found for painful conditions, but these did not depend on the method of assessment. Associations were not found for excessive alcohol consumption irrespective of the method of assessment. CONCLUSIONS: These findings help to allay concerns that associations between childhood adversities and health outcomes during adulthood are merely artefacts of recall bias. In this study, retrospective and prospective assessment strategies produced similar results.

Patterns of disability, care needs, and quality of life of people with Parkinson's disease in a general population sample.

OBJECTIVE: To quantify patterns of disability, care needs, and quality of life in a national community-dwelling sample of people with Parkinson's disease (PD) in Canada. METHODS: Data from Statistics Canada's Participation and Activity Limitations Survey was used in the analysis. This survey is a post-censual survey that collected data from 28,630 household residents with reported activity limitations in the 2006 Canadian census. Frequencies of specific impairments and care needs as well as mean quality of life ratings were estimated. These estimates were adjusted for age and sex using linear regression modeling. Sampling weights were used to adjust for design effects, ensuring that the estimates were representative of the national population. RESULTS: The estimated prevalence of PD was 0.1% (100 per 100,000 people), consistent with previous estimates. People with PD reported a significantly elevated prevalence of mobility (88.5%), communication (47.9%), pain (68.6%), memory (26.2%) and seeing (47.7%) limitations relative to those with disabilities of other origins. Significantly more people with PD required help with instrumental activities of daily living and activities of daily living. Health related quality of life, measured by the health utility index, was significantly lower in people with PD (mean value 0.46) compared to disabled people without PD (mean value 0.70). CONCLUSIONS: People living in the community with PD have a significant burden of disability. Health related quality of life is also quite poor in people with PD compared to other disabled populations. This study helps to quantify the significant care needs of people with PD.