Don MacDonald

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 (≥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%, ≥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.

Long-Term Prognosis and Comorbidities Associated with Psoriasis in the Newfoundland and Labrador Founder Population:

Background: Psoriasis is a common chronic immune-mediated inflammatory disorder of the skin with several associated comorbidities. Objective: To assess the prevalence of comorbidities in a cohort of psoriasis patients within the Canadian province of Newfoundland and Labrador (NL). Methods: This cross-sectional observational study investigated hospital-coded comorbidities associated with psoriasis in comparison to the general NL hospitalized population. Results: Patients died significantly younger than the general population, with patients having an earlier disease onset (≤ 25 years) dying at a younger age than those with a later onset (> 25 years; 59.3 vs 71.2; p = .001). Patients were hospitalized more frequently for several system disorders than the general population, and a potential association was observed between prognostic factors such as age at onset, disease severity, and HLA-Cw6 genotype and certain comorbid conditions. Conclusion: This study supports an association between psoriasis and other conditions, such as circulatory and endocrine diseases.

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 patients 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.

Systematized nomenclature of medicine clinical terms (SNOMED CT) to represent computed tomography procedures

OBJECTIVE To evaluate the ability of systematized nomenclature of medicine clinical terms (SNOMED CT) to represent computed tomography procedures in computed tomography dictionaries used in the Canadian province of Newfoundland and Labrador. METHODS This study was conducted in two stages. In the first stage computed tomography dictionaries were collected and consolidated to one master list. The duplicated procedure names were deleted from the list. In the second stage the unique data items from the master list were matched with the SNOMED CT concepts. Sensitivity, specificity, and positive and negative predictive values of SNOMED CT were investigated. RESULTS After eliminating 680 duplicate procedures from the total of 833, the study sample consisted of 153 data items. For pre-coordination, SNOMED CT had sensitivity of 56% and for post-coordination SNOMED CT had sensitivity of 98%. CONCLUSION Our results suggest that SNOMED CT is a valid nomenclature for representing computed tomography procedures.

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

&NA; 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. HighlightsSpina bifida (SB), a neural tube birth defect occurring within the first four weeks of pregnancy and is the most common life disabling birth defect.In this neurological condition the spinal column fails to develop properly—one or more vertebrae do not form completely leaving a gap in the spine.The aetiology of SB is unknown, but both genetic and environmental risk factors are considered important for its onset and progression.Risk factors for onset include maternal obesity, paternal Agent Orange exposure and lack of folic acid intake in the periconceptional period.All the risk factors mentioned above are modifiable hence should be targeted as preventative strategies to reduce the burden of SB.

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.

Determinants of neurological disease: Synthesis of systematic reviews

&NA; 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. HighlightsWith population aging, the burden of neurological disease is increasing worldwide.Understanding the factors affecting the onset and progression of neurological disease through systematic review is essential for the development of strategies to reduce the burden of these diseases.Systematic review identified biological, demographic, environmental, genetic, lifestyle and pharmacological risk factors for specific neurological conditions.Several risk factors were associated with the onset of multiple conditions. Pesticides, for example, were associated with an increased risk of Alzheimers disease, amyotrophic lateral sclerosis, primary brain tumours, and Parkinsons disease.Helmet use was associated with a reduction in onset of neurotrauma, as well as all neurologic conditions for which head injury was a risk factor.The findings presented here should be viewed as provisional, pending a more in‐depth evaluation of the weight of evidence.Further research will also serve to fill current data gaps, particularly regarding risk factors for the progression of neurological disease.In the interim, the modifiable risk factors may be considered as potential candidates for the development of targeted interventions to reduce the burden of neurological disease in Canada and internationally.

Epidemiology of severe burn among children in Newfoundland and Labrador, Canada

PURPOSE The objective of this study was to identify the epidemiologic characteristics of childhood burns in the province of Newfoundland and Labrador. METHODS A population-based study was carried out on children aged 0-16 years who were hospitalized due to burns in Newfoundland and Labrador between April 1995 and March 2001. Hospital and mortality data were obtained from the provincial hospital admission database and Mortality System, respectively. The Newfoundland and Labrador population was considered as a whole and as two separate geographic areas. RESULTS A total of 157 hospital admissions due to burns were identified during the study period. The rate of burns requiring hospitalization in the province was 22.3 per 100,000 person-years (P-Y). The rates for males and females was 27.7 and 16.6 per 100,000 P-Y, respectively (P=0.006). Infants (0-1 year) had the highest rate of burn (88.8 per 100,000 P-Y) followed by children aged 2-4 years (26.0 per 100,000 P-Y) (P<0.0001). Labrador, a region with high Aboriginal population (51.4 per 100,000 P-Y), had a higher rate of burn compared to Newfoundland (20.3 per 100,000 P-Y) (P<0.0001). Median age of patients with burns was 2 years for the island portion of the province and 9 years in Labrador (P<0.01). Overall, scald burn (52.2%) was the most frequent type of burn followed by flame (32.5%). In the island portion of the province, scald burn was the most common type of burn (56.4%), while in Labrador flame was the most frequent type (66.7%). Overall mortality rate due to burns was 0.9 per 100,000 P-Y. CONCLUSION Age (infants) and sex (male) are factors associated with burn in Newfoundland and Labrador. Study results indicate a difference in the epidemiologic pattern of burn between the island portion of the province, Newfoundland, and mainland Labrador. It is recommended that preventive programs be directed towards high risk groups to reduce the incidence of burns.

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

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.

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.