An Investigation of Comorbid Disease and Health Service Utilization Among Patients With Moderate to Severe Psoriasis in Newfoundland and Labrador.

Psoriasis is an inflammatory skin condition affecting 2% to 3% of the population and is associated with several comorbidities, including cardiovascular disease, depression, inflammatory bowel disease, metabolic syndrome, mood disorder, psoriatic arthritis, and weight gain. Psoriasis is treated with a number of topical and systemic therapies, including biologic drugs that directly target proinflammatory cytokines. This cross-sectional retrospective study investigated comorbid conditions reported in the Newfoundland and Labrador psoriasis population, outcomes associated with therapeutic treatment, and use of health care resources. Of the psoriasis comorbidities investigated, psoriatic arthritis was significantly associated with the use of biologic therapy while a failure to respond to biologics was associated with a higher incidence of cardiovascular disease. Patients responsive to biologic treatment had fewer hospital stays than patients treated with other therapies. Our results suggest that biologic therapies have a cardioprotective effect and reduce the number of hospital visits in patients whose symptoms are responsive to treatment.

The Newfoundland and Labrador Bariatric Surgery Cohort Study: Rational and Study Protocol.

BACKGROUND: In Canada, there has been a disproportionate increase in adults with Class II (BMI 35.0-39.9 kg/m2) or Class III obesity (BMI ≥ 40 kg/m2) affecting 9 % of Canadians with increases projected. Individuals affected by severe obesity (BMI ≥ 35) are at increased risk of high blood pressure, cardiovascular disease, diabetes, cancer, impaired quality of life, and premature mortality. Bariatric surgery is the most effective treatment for severe obesity. Laparoscopic sleeve gastrectomy (LSG), a relatively new type of bariatric surgery, is growing in popularity as a treatment. The global prevalence of LSG increased from 0 to 37.0 % between 2003 and 2013. In Canada and the US, between 2011 and 2013, the number of LSG surgeries increased by 244 % and LSG now comprises 43 % of all bariatric surgeries. Since 2011, Eastern Health, the largest regional health authority in Newfoundland and Labrador (NL), Canada has performed approximately 100 LSG surgeries annually. METHODS: A population-based prospective cohort study with pre and post surgical assessments at 1, 3, 6, 12, 18, 24 months and annually thereafter of patients undergoing LSG. This study will report on short - to mid-term (2-4 years) outcomes. Patients (n = 200) followed by the Provincial Bariatric Surgery Program between 19 and 70 years of age, with a BMI between 35.0 and 39.9 kg/m2 and an obesity-related comorbidity or with a BMI ≥ 40 kg/m2 are enrolled. The study is assessing the following outcomes: 1) complications of surgery including impact on nutritional status 2) weight loss/regain 3) improvement/resolution of comorbid conditions and a reduction in prescribed medications 4) patient reported outcomes using validated quality of life tools, and 5) impact of surgery on health services use and costs. We hypothesize a low complication rate, a marked reduction in weight, improvement/resolution of comorbid conditions, a reduction in related medications, improvement in quality of life, and a decrease in direct healthcare use and costs and indirect costs compared to pre-surgery. DISCUSSION: Limited data on the impact of LSG as a stand-alone procedure on a number of outcomes exist. The findings from this study will help to inform evidence-based practice, clinical decision-making, and the development of health policy.

Do Biologics Protect Patients With Psoriasis From Myocardial Infarction? A Retrospective Cohort.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory disorder that affects approximately 2% to 3% of the population, which translates to 17 million in North America and Europe and approximately 170 million people worldwide. Although psoriasis can occur at any age, most cases develop before age 40 years. Some larger studies have noted bimodal age at onset with the first peak occurring at approximately age 30 years and the second peak at around 55 to 60 years, but most patients have a younger age of onset (15-30 years). Psoriasis is associated with multiple comorbidities, decreased quality of life, and decreased longevity of life. Two recent systematic reviews and a meta-analysis concluded that psoriasis patients are at increased risk of major adverse cardiovascular events. Multiple studies confirm that many of the comorbidities found in patients with psoriasis are also important risk factors for cardiovascular disease, stroke, diabetes mellitus, hypertension, hyperlipidemia, obesity, and metabolic syndrome. METHODS: We conducted a retrospective cohort study using charts from a dermatology clinic combined with an administrative database of patients with moderate to severe psoriasis in Newfoundland and Labrador, Canada. We examined the role of clinical predictors (age of onset of psoriasis, age, sex, biologic use) in predicting incident myocardial infarction (MI). RESULTS: Logistic regression revealed that age of onset (odds ratio [OR], 8.85; P = .005), advancing age (OR, 1.07; P < .0001), and being male (OR, 3.64; P = .018) were significant risk factors for the development of MI. Neither biologic therapy nor duration of biologic therapy were statistically significant risk factors for the development of MI. Our study found that in patients with psoriasis treated with biologics, there was a nonsignificant trend in reduced MI by 78% (relative risk, 0.18; 95% confidence interval, 0.24-1.34; P = .056). CONCLUSION: Our study demonstrated a trend toward decreased MI in patients with moderate to severe psoriasis on biologics. Patients with an early age of onset of psoriasis (<25 years) were nearly 9 times more likely to have an MI. Clinicians should consider appropriate cardiovascular risk reduction strategies in patients with psoriasis.

Adverse drug reactions in elderly hospitalized patients: a 12-year population-based retrospective cohort study.

BACKGROUND: Although research has identified some risk factors for first-time adverse drug reactions (ADRs), little is known about the risks associated with the number of ADRs. Modeling ADR counts is relatively complex because of the rarity of the events, requiring careful consideration of appropriate models that best present the observed data. OBJECTIVE: To determine the incidence of ADRs among elderly hospitalized patients, assess patient-related risk factors for the number of ADRs, and review drug classes commonly responsible for ADRs. METHODS: This retrospective cohort study used a population-based large administrative database on hospital separations from all acute care hospitals in the Canadian province of Newfoundland and Labrador. Patients aged 65 years or older with at least 1 hospital admission from April 1, 1995, to March 31, 2007, were included. Comorbidities, Charlson Comorbidity Index (CCI), and sociodemographic factors were assessed as predictors of ADR counts. A zero-inflated negative binomial regression model was used for analysis. RESULTS: The study cohort contained 64,446 patients. The incidence of ADRs was 15.2 per 1000 person-years (95% CI 14.8 to 15.7). Of those having an ADR, 15.4% had recurrent ADRs. The most common drug category implicated in ADRs was cardiovascular agents (17.7%). A dose-response relationship was found between CCI and ADR counts (rate ratio [RR] 1.67, 95% CI 1.41 to 1.98 for CCI 2-3; RR 2.38, 95% CI 1.98 to 2.87 for CCI 4-5; and RR 3.83, 95% CI 3.21-4.57 for CCI ≥6). Comorbid conditions including congestive heart failure (RR 1.58, 95% CI 1.33 to 1.89), diabetes (RR 2.42, 95% CI 1.64 to 3.56), and cancer (RR 3.12, 95% CI 2.58 to 3.76) were strong predictors. Rural areas (RR 1.22, 95% CI 1.01 to 1.46) were associated with increased risk for ADRs, whereas age and sex had no effect. CONCLUSIONS: Comorbidity from chronic diseases and severity of illness, rather than individual characteristics (advancing age and sex), increased the likelihood of ADRs. Changes in the delivery of care focusing on the monitoring of prescribed drugs in elderly patients with comorbidities could mitigate ADRs.

Referring physicians' perceived benefits of PACS: a regional survey pre- and post-PACS implementation.

Referring physicians in theWestern Health Authority of Newfoundland and Labrador were administered a survey before and after PACS was implemented across all acute sites in the province.The survey had 31.7% and 35.0% response rates, respectively. There was considerable support found for PACS both pre- and post-implementation in the areas of exam access and review, PACS functionality, quality of reports, efficiency, and site-to-site professional consultations.There was limited support that PACS reduced hospital length of stay. Surveys such as the one employed in this study provide an opportunity to measure the perceived benefit and challenges of PACS in a relatively cost effective manner.

Adverse drug events in adult patients leading to emergency department visits.

BACKGROUND: Adverse drug events (ADEs) occurring in the community and treated in emergency departments (EDs) have not been well studied. OBJECTIVE: To determine the prevalence, severity, and preventability of ADEs in patients presenting at EDs in 2 university-affiliated tertiary care hospitals in the Canadian province of Newfoundland and Labrador. METHODS: A retrospective chart review was conducted on a stratified random sample (n = 1458) of adults (> or =18 y) who presented to EDs from January 1 to December 31, 2005. Prior to the chart review, the sample frame was developed by first eliminating visits that were clearly not the result of an ADE. The ED summary of each patient was initially reviewed by 2 trained reviewers in order to identify probable ADEs. All eligible charts were subsequently reviewed by a clinical team, consisting of 2 pharmacists and 2 ED physicians, to identify ADEs and determine their severity and preventability. RESULTS: Of the 1458 patients presenting to the 2 EDs, 55 were determined to have an ADE or a possible ADE (PADE). After a sample-weight adjustment, the prevalence of ADEs/PADEs was found to be 2.4%. Prevalence increased with age (0.7%, 18-44 y; 1.9%, 45-64 y; 7.8%, > or =65 y) and the mean age for patients with ADEs was higher than for those with no ADEs (69.9 vs 63.8 y; p < 0.01). A higher number of comorbidities and medications was associated with drug-related visits. Approximately 29% of the ADEs/PADEs identified were considered to be preventable, with 42% requiring hospitalization. Cardiovascular agents (37.4%) were the most common drug class associated with ADEs/PADEs. CONCLUSIONS: Adult ADE-related ED visits are frequent in Newfoundland and Labrador, and in many cases are preventable. Further efforts are needed to reduce the occurrence of preventable ADEs leading to ED visits.

Adverse drug events among children presenting to a hospital emergency department in Newfoundland and Labrador, Canada.

OBJECTIVES: The aim of this study was to examine epidemiologic characteristics of Adverse Drug Events (ADEs) among children and adolescents presenting to an Emergency Department (ED) in Newfoundland and Labrador (NL), Canada. MATERIALS AND METHODS: This study was conducted in three phases and included an ED chart review of visits to the Janeway Hospital in St. John's, NL, between 27th April 2006 and 26th April 2007. The first phase narrowed the sampling frame by excluding visits highly unlikely to be drug-related. In the second phase, a random sample of ED charts was selected for review by two research nurses using a Trigger Assessment Tool that classified ED visits according to their likelihood of being drug related ('high', 'moderate', 'low', 'very low', or 'no' probability). The third phase included a full chart review of all 'high', 'moderate', 'low', and 'very low' probability ADE charts, carried out independently by two ED pediatricians and two clinical pharmacists. Each ADE was also scored for severity and preventability, and consensus was reached among all four reviewers during meetings held at the end of this phase. RESULTS: In this study, 69 patients presented to the ED either due to an ADE or a possible ADE (PADE). After a sample-weight adjustment, the prevalence of ADEs/PADEs was found to be 2.1%. The number of co-morbidities was inversely associated with medication-related visits. There was no significant difference found between patients with and without medication related visits with respect to mean age of the patient and the mean number of current medications being taken. Of the 69 confirmed ADE/PADEs, none were fatal, six (8.7%) were serious/life-threatening, and 63 (91.3%) were considered significant. Antimicrobial agents (45.0%) were the most common drug classes associated with ADEs/PADEs. Approximately 20% of the 69 ADEs/PADEs identified were considered preventable. CONCLUSIONS: In St. John's NL, emergency department visits as a result of ADEs are common among the pediatric population and in many cases preventable. Age and number of current medications do not appear to be associated with ED visits related with ADE. Antimicrobial agents were found to be to the cause of most ADEs/PADEs.

Role of social support in the relationship between sexually transmitted infection and depression among young women in Canada.

BACKGROUND: Individuals with a self-reported history of sexually transmitted infection (STI) are at high risk for depression. However, little is known about how social support affects the association between STI and depression among young women in Canada. METHODS: Data were drawn from the Canadian Community Health Survey (CCHS), conducted in 2005. A total of 2636 women aged 15-24 years who provided information on STI history were included in the analysis. Depression was measured by a depression scale based on the Composite International Diagnostic Interview Short-Form (CIDI-SF). The 19-item Medical Outcomes Study (MOS) Social Support Survey assessed functional social support. A log-binomial model was used to estimate the prevalence ratio (PR) for self-reported STI history associated with depression and to assess the impact of social support on the association. RESULTS: The adjusted PR for self-reported STI history associated with depression was 1.61 (95% CI, 1.03 to 2.37), before social support was included in the model. The association between STI history and depression was no longer significant when social support was included in the model (adjusted PR, 1.28; 95% CI, 0.83 to 1.84). The adjusted PRs for depression among those with low and intermediate levels of social support versus those with a high level of social support were 5.62 (95% CI, 3.50 to 9.56) and 2.19 (1.38 to 3.68), respectively. CONCLUSIONS: Social support is an important determinant of depression and reduces the impact of self-reported STI on depression among young women in Canada.

Diabetes and its impact on health-related quality of life: a life table analysis.

PURPOSE: To investigate the health burden of diabetes and determine its impact on health-related quality of life (HRQOL) in a population with a high prevalence of chronic conditions. METHODS: A representative sample of the Canadian province of Newfoundland and Labrador (NL) was used to estimate prevalence of diabetes and mean health utility index (HUI), a utility-based measure of HRQOL. Diabetes-deleted life expectancy (LE) and health-adjusted life expectancy (HALE) were derived to measure HRQOL. RESULTS: Diabetic individuals comprised 6.8% of the sample and accounted for 14% of total deaths from 2001 to 2005. Life Expectancy at age 15 was 61.3 years for men and 66.7 years for women, of which 53.0 and 57.0 years, respectively, were spent with perfect health (86.4 and 85.5%). Eliminating diabetes would extend both the overall LE and HALE for men by 1.3 and 1.4 years, and women by 2.0 and 1.7 years, respectively. People with diabetes had a significantly lower HRQOL than people without diabetes (mean HUI: 0.78 vs. 0.88, P < 0.01). CONCLUSION: The burden of illness from diabetes in NL is considerable. Using cause-eliminated LE and HALE provides a robust approach for assessing HRQOL that may have important implications for diabetes surveillance, prevention, and management strategies.

Unintentional injuries among children and adolescents in Aboriginal and non-Aboriginal communities, Newfoundland and Labrador, Canada.

OBJECTIVES: To compare epidemiologic characteristics of unintentional injuries among children and adolescents in Aboriginal and non-Aboriginal communities in the Province of Newfoundland and Labrador (NL), Canada. STUDY DESIGN: A comparative population-based study of unintentional injuries among individuals 0-19 years was conducted among Aboriginal and non-Aboriginal communities in NL. METHODS: The provincial hospital discharge and mortality data were analyzed for a 6-year period, April 1995 to March 2001. Rates and rate ratios related to hospital discharge and mortality due to unintentional injuries were calculated to assess variation of rates. The 2-independent sample binomial proportion test was used to compare rates between Aboriginal and non-Aboriginal communities. RESULTS: The overall hospital discharge rates of unintentional injury in Aboriginal and non-Aboriginal communities were 1,132.0 and 614.2 per 100,000 population, respectively (p(2)<0.001). For both Aboriginal and non-Aboriginal communities, the rate among males was higher than that of females (p(2)<0.001). The mortality rate was found to be higher in Aboriginal communities than non-Aboriginal communities (84.3 vs. 10.2 per 100,000 population) (p(2)<0.001). CONCLUSIONS: The rate of unintentional injury among children and adolescents in Aboriginal communities is higher than non-Aboriginal communities. Sex (male) and place of residence (Aboriginal communities) were strong predictors of unintentional injury in NL.

Molecular phylogeny of sturgeon mimiviruses and Bayesian hierarchical modeling of their effect on wild Lake Sturgeon (Acipenser fulvescens) in Central Canada.

Sturgeon mimiviruses can cause a lethal disease of the integumentary systems of sturgeon (Acipenseridae). Here we provide phylogeographic evidence that sturgeon mimivirus is endemic in endangered populations of wild Lake Sturgeon within Canada's Hudson Bay drainage basin. Namao virus (NV) variants were diagnosed in 24% of Lake Sturgeon samples (n = 1329) collected between 2010-2015. Lake Sturgeon populations with the highest virus prevalence were from the Nelson River (58%) in 2015, Saskatchewan River (41%) in 2010 and South Saskatchewan River (36%) in 2011. Bayesian phylogenetic reconstructions suggested that four NV variants, designated HBDB I-IV, co-circulate temporally and spatially within and between the genetically and biogeographically distinct Lake Sturgeon populations. Evidence from recapture studies suggested that Lake Sturgeon across the basin are persistently infected with NV at prevalence and titer (103.6 equivalent plasmid copies per µg DNA) levels consistent with the hypothesis that wild Lake Sturgeon populations serve as a maintenance population and reservoir for sturgeon mimiviruses. Bayesian hierarchical modeling of NV in the Landing River population of Lake Sturgeon suggested that host weight and age were the best predictors of sturgeon mimivirus presence and titer, respectively, whereas water flow rate, level and temperature, and number of previous captures did not significantly improve model fit. A negative relationship was estimated between sturgeon mimivirus presence and Lake Sturgeon weight and between virus titer and Lake Sturgeon age.

Characterizing toxicity of metal-contaminated sediments from the Upper Columbia River, Washington, USA, to benthic invertebrates.

Sediments from the Upper Columbia River, Washington, USA, are contaminated with metals from smelting operations. We conducted short-term and long-term tests with the midge Chironomus dilutus and the amphipod Hyalella azteca and short-term tests with the freshwater mussel Lampsilis siliquoidea with 54 sediments from the Upper Columbia River to characterize thresholds for toxicity of metals to benthic invertebrates. Test sediments were screened for toxicity by comparisons with low-metal reference sediments. Toxic effects on amphipods occurred primarily in sediments from the upstream (riverine) reach, and toxic effects on midges occurred in sediments from both the upstream reach and the downstream (reservoir) reach. Little toxicity was observed in mussel tests. Toxicity thresholds (20% effect concentrations [EC20s]) for metals in sediment and porewater were estimated from logistic concentration-response models. Copper (Cu) concentrations in the simultaneously extracted metal fraction of sediments and bioavailable Cu in porewater, as characterized by biotic ligand models, had consistent associations with toxicity endpoints. Concentration-response models for sediment Cu produced EC20s for 6 endpoints, with long-term amphipod survival and reproduction being the most sensitive. A logistic regression model fitted to an endpoint sensitivity distribution for sediment Cu predicted that approximately one-half of the sediments tested would be toxic to at least one endpoint and that approximately 20% of test sediments would be toxic to more than half of the endpoints. These results indicate that sediments from the upstream reach of the Upper Columbia River, which contain high concentrations of metals associated with slags, cause a wide range of toxic effects in laboratory tests and are likely to have adverse effects on benthic invertebrate communities. Environ Toxicol Chem 2018;37:3102-3114. Published 2018 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Hospitalization due to pneumonia among Innu, Inuit and non-Aboriginal communities, Newfoundland and Labrador, Canada.

OBJECTIVES: The objective of this study was to compare hospitalization rates due to pneumonia between Innu/Inuit communities in Labrador and non-Aboriginal communities on the Northern Peninsula of Newfoundland, Canada. METHODS: This is a comparative study using data on hospitalization due to pneumonia for the period from April 1, 1995 to March 31, 2001, for the Innu/Inuit communities in Labrador and a sample of non-Aboriginal communities on the Northern Peninsula of Newfoundland. Data were obtained from the provincial hospital database. Hospitalization rates among the study groups were compared by age, gender, and type of pneumonia. RESULTS: The hospitalization rate due to pneumonia for the Innu/Inuit communities was 11.6 compared to 3.0 per 1000 population for non-Aboriginal communities (p<0.01x10(-4)). Among the Innu/Inuit communities, infants had the highest rate of hospitalization due to pneumonia (93.4 per 1000 population), while the elderly (10.2 per 1000 population) were found to have the highest rate among the non-Aboriginal sample. Overall hospitalization rate for the Innu communities (16.9 per 1000 population) was higher than that for Inuit communities (8.4 per 1000 population) (p<0.01x10(-4)). CONCLUSIONS: Aboriginal communities, particularly the Innu communities, had higher rates of hospitalization due to pneumonia compared to the non-Aboriginal sample. Findings of this study will be used as a foundation for more specific studies in an effort to increase our understanding of pneumonia and associated risk factors.

A systematic review of the risks factors associated with the onset and natural progression of spina bifida.

The purpose of this study was to systematically assess and synthesize the world literature on risk factors for the onset and natural progression of spina bifida, thereby providing a basis for policy makers to identify appropriate risk management measures to mitigate the burden of disease in Canada. Searches of several health literature databases from inception to February 2013 were conducted by a health sciences librarian. A total of three meta-analyses that studied a risk factor for the onset of spina bifida were included. Pooled results showed that paternal exposure to Agent Orange (RR=2.02; 95% CI 1.48-2.74) and maternal obesity prior to pregnancy (OR=2.24; 95% CI 1.86-2.74) each increased the risk of having a child with spina bifida. Paternal exposure to organic solvents was also close to the limit of significance (OR=1.59; 95% CI 0.99-2.56). A total of 63 observational studies, encompassing hundreds of potential risk factors, were included for risk factors for the onset of disease. One meta-analysis and four observational studies examined the impact of genetic risk factors. Only specified mutations in the 5,10-methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase (DHFR) genes were found to be linked to disease onset. One observational study evaluated a risk factor for the natural progression of disease. An extensive number of potential risk factors for the onset of spina bifida have been studied, though most lack sufficient evidence to confirm an association. Currently, strong evidence exists to suggest a causal association for maternal obesity prior to pregnancy, and paternal exposure to Agent Orange.

Factors associated with the onset and progression of neurotrauma: A systematic review of systematic reviews and meta-analyses.

Neurotrauma, including traumatic brain injury (TBI) and spinal cord injury (SCI), is a preventable condition that imposes an important burden on the Canadian society. In this study, the current evidence on risk factors for the onset and progression of neurotrauma is systematically reviewed and synthesized. Searches of the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE), Medline and Medline in Process (via OVID), EMBASE and PsycINFO from inception to February 2013 were conducted to identify relevant systematic reviews and meta-analyses published in English or French. Two referees screened and assessed the quality of the studies using the AMSTAR tool. Thirty-two studies examined at least one risk factor for the onset of neurotrauma. Thirteen studies passed the quality assessment and the majority evaluated the impact of protective equipment in sports. Helmets effectively reduce TBI from bicycling, skiing, snowboarding, ice hockey and motorcycling. There was no evidence of a protective effect of helmets for SCI. No studies contributed evidence on risk factors for the onset of SCI. Of two studies examining risk factors for the progression of neurotrauma, only injury severity was found to be associated with poorer post-injury outcomes. Substantial evidence supports the use of helmets for the prevention of TBI in sports and motorcycling and face shields in ice hockey. Addressing bicycle helmet legislation across Canada may be an effective option for reducing TBI caused by bicycle accidents. Limited evidence on relevant risk factors for spinal cord injuries and neurotrauma progression was available.

A systematic review of the risks factors associated with the onset and natural progression of hydrocephalus.

The purpose of this study was to systematically assess and synthesize the world literature on risk factors for the onset and natural progression of hydrocephalus, thereby providing a basis for policy makers to identify appropriate risk management measures to mitigate the burden of disease in Canada. Evidence for risk factors was limited for both onset and progression. Two meta-analyses that examined a risk factor for onset met the inclusion criteria. One found a significant protective effect of prenatal vitamins among case control studies, but not cohort/randomized controlled trials (RCTs). The second found maternal obesity to be a significant risk factor for congenital hydrocephalus. Significant risk factors among 25 observational studies included: biological (multiple births, maternal parity, common cold with fever, maternal thyroid disease, family history, preterm birth, hypertension, ischemic heart disease, ischemic ECG changes, higher cerebrospinal fluid protein concentration following vestibular schwannoma); lifestyle (maternal obesity, high-density lipoprotein (HDL) cholesterol, maternal diabetes, maternal age), healthcare-related (caesarean section, interhospital transfer, drainage duration following subarachnoid hemorrhage, proximity to midline for craniectomy following traumatic brain injury); pharmaceutical (prenatal exposure to: tribenoside, metronidazole, anesthesia, opioids); and environmental (altitude, paternal occupation). Three studies reported on genetic risk factors: no significant associations were found. There are major gaps in the literature with respect to risk factors for the natural progression of hydrocephalus. Only two observational studies were included and three factors reported. Many risk factors for the onset of hydrocephalus have been studied; for most, evidence remains limited or inconclusive. More work is needed to confirm any causal associations and better inform policy.

A systematic review of the risks factors associated with the onset and natural progression of epilepsy.

Epilepsy is a neurological condition that affects more than 50 million individuals worldwide. It presents as unpredictable, temporary and recurrent seizures often having negative physical, psychological and social consequences. To inform disease prevention and management strategies, a comprehensive systematic review of the literature on risk factors for the onset and natural progression of epilepsy was conducted. Computerized bibliographic databases for systematic reviews, meta-analyses, observational studies and genetic association studies published between 1990 and 2013 describing etiological risk factors for epilepsy was searched. The quality of systematic reviews was validated using the AMSTAR tool and articles were reviewed by two referees. A total of 16,958 articles went through stage one review of abstracts and titles. A total of 76 articles on genetic and non-genetic risk factors for the onset and progression of epilepsy met the eligibility criteria for data extraction. Dozens of risk factors were significantly associated with onset of epilepsy. Inconsistent levels of evidence for risk of onset included family history of epilepsy, history of febrile seizures, alcohol consumption, CNS and other infections, brain trauma, head injury, perinatal stroke, preterm birth and three genetic markers. Limited evidence showed that symptomatic epilepsy, focal seizures/syndromes, slow waves on EEG, higher seizure frequency, high stress or anxiety, and lack of sleep decreased the odds of seizure remission. High quality studies were rare and while a large body of work exists, relatively few systematic reviews were found.

Association of insulin dosage with mortality or major adverse cardiovascular events: a retrospective cohort study.

BACKGROUND: Existing studies have shown conflicting evidence regarding the safety of exogenous insulin therapy in patients with type 2 diabetes. In particular, observational studies have reported an increased risk of death and cardiovascular disease among users of higher versus lower doses of insulin. We aimed to quantify the association between increasing dosage of insulin exposure and death and cardiovascular events, while taking into account time-dependent confounding and mediation that might have biased previous studies. METHODS: We did a cohort study using primary care records from the UK-based Clinical Practice Research Datalink (CPRD). New users of metformin monotherapy were identified in the period between Jan 1, 2001, and Dec 31, 2012. We then identified those in this group with a new prescription for insulin. Insulin exposure was categorised into groups according to the mean dose (units) per day within 180-day time segments throughout each patient's follow-up. Relative differences in mortality and major adverse cardiovascular events (non-fatal myocardial infarction, non-fatal stroke, cardiovascular-related mortality) were assessed using conventional multivariable Cox proportional hazards models. Marginal structural models were then applied to reduce bias introduced by the time-dependent confounders affected by previous treatment. FINDINGS: We identified 165 308 adults with type 2 diabetes in the CPRD database. After applying our exclusion criteria, 6072 (mean age 60 years [SD 12·5], 3281 [54%] men, mean HbA1c 8·5% [SD 1·75], and median follow-up 3·1 years [IQR 1·7-5·3) were new add-on insulin users and were included in the study cohort; 3599 were new add-on insulin users and were included in the subcohort linked to hospital records and death certificate information. Crude mortality rates were comparable between insulin dose groups; <25 units per day (46 per 1000 person-years), 25 to <50 units per day (39 per 1000 person-years), 50 to <75 units per day (27 per 1000 person-years), 75 to <100 units per day (34 per 1000 person-years), and at least 100 units per day (32 per 1000 person-years; p>0·05 for all; mean rate of 31 deaths per 1000 person-years [95% CI 29-33]). With adjustment for baseline covariates, mortality rates were higher for increasing insulin doses: less than 25 units per day [reference group]; 25 to <50 units per day, hazard ratio (HR) 1·41 [95% CI 1·12-1·78]; 50 to <75 units per day, 1·37 [1·04-1·80]; 75 to <100 units per day, 1·85 [1·35-2·53]; and at least 100 units per day, 2·16 [1·58-2·93]. After applying marginal structural models, insulin dose was not associated with mortality in any group (p>0·1 for all). INTERPRETATION: In conventional multivariable regression analysis, higher insulin doses are associated with increased mortality after adjustment for baseline covariates. However, this effect seems to be confounded by time-dependent factors such as insulin exposure, glycaemic control, bodyweight gain, and the occurrence of cardiovascular and hypoglycaemic events. This study provides reassurance of the overall safety of insulin use in the treatment of type 2 diabetes and contributes to our understanding of the contrasting conclusions from non-randomised and randomised studies regarding dose-dependent effects of insulin on cardiovascular events and mortality. FUNDING: Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and the Newfoundland and Labrador Research and Development Corporation.

Determinants of neurological disease: Synthesis of systematic reviews.

Systematic reviews were conducted to identify risk factors associated with the onset and progression of 14 neurological conditions, prioritized as a component of the National Population Health Study of Neurological Conditions. These systematic reviews provided a basis for evaluating the weight of evidence of evidence for risk factors for the onset and progression of the 14 individual neurological conditions considered. A number of risk factors associated with an increased risk of onset for more than one condition, including exposure to pesticides (associated with an increased risk of AD, amyotrophic lateral sclerosis, brain tumours, and PD; smoking (AD, MS); and infection (MS, Tourette syndrome). Coffee and tea intake was associated with a decreased risk of onset of both dystonia and PD. Further understanding of the etiology of priority neurological conditions will be helpful in focusing future research initiatives and in the development of interventions to reduce the burden associated with neurological conditions in Canada and internationally.

Childhood type 1 diabetes mellitus in Newfoundland and Labrador, Canada.

The aim of this study was to calculate incidence and hospitalization rates of childhood type 1 diabetes mellitus (T1DM) in Newfoundland and Labrador, and to assess hospitalization trends and associated factors. Data for all patients aged 0-19 years with a diagnosis of T1DM was obtained from the clinical database management system (CDMS) for a 7-year period between April 1, 1995 and March 31, 2002. Incidence was calculated for the 0-7 years age group. A total of 894 T1DM hospital separations among children aged 0-19 years were identified, representing a hospitalization rate of 88.6 per 100,000 person-years (P-Y). The CDMS identified 518 incidences of hospitalization (51.2 per 100,000 P-Y). The overall hospitalization rate increased over the study period (P((2))=0.065). Hospitalization rates for males and females were 77.3 and 100.2 per 100,000 P-Y, respectively (P((2))=0.00011). Of the 894 hospitalization separations, 216 hospitalizations were for diabetic ketoacidosis (DKA) (21.4 per 100,000 P-Y). Female gender and older age were found to be predictive factors of DKA. The incidence rate of T1DM among children aged 0-7 years was 19.0 per 100,000 P-Y. Newfoundland and Labrador has one of the highest incidence rates of T1DM in the world. Hospitalization rates for DKA and non-DKA increased slightly over the study period. Age and sex patterns suggest that DKA is a particular challenge among adolescent girls. Preventive strategies are needed, particularly in areas of the province with the highest rates.