Increased Prevalence of Bell's Palsy in First Nations Populations with Type 2 Diabetes Mellitus in Manitoba.

Bell's palsy is acute facial palsy due to inflammation involving the facial nerve related to infections. Rates have not been noted to differ by ethnicity. We studied the lifetime prevalence in First Nations and all other Manitobans in people with type 2 diabetes mellitus aged 7 and older in 2013-2014 and 2016-2017.

Bariatric surgery decreases prescription drug costs for metabolic syndrome: a Canadian population-based cohort study.

Background: Obesity is a chronic disease that is significantly linked to metabolic syndrome. Bariatric surgery is considered the most effective treatment for obesity resulting in long-term weight loss and comorbidity resolution. Prior studies have demonstrated the overall cost effectiveness of bariatric surgery; however, there is little data regarding direct pharmaceutical costs.

Impact of being taken into out-of-home care: a longitudinal cohort study of First Nations and other child welfare agencies in Manitoba, Canada.

Background: Across Canada, Child Protection Services (CPS) disrupt Indigenous families by apprehending their children at alarmingly high rates. The harms borne by children in out-of-home care (OoHC) have been extensively documented. We examined the impact of OoHC on Manitoba children's health and legal system outcomes to provide rigorous evidence on how discretionary decision-making by CPS agencies can affect these outcomes.

Trend in Prescription Medication Utilization for Opioid Use Disorder and Alcohol Use Disorder From 2015 to 2021: A Population-wide Study in a Canadian Province.

Objective: To examine the quarterly incidence and prevalence of medications for opioid use disorder (OUD) and alcohol use disorder (AUD) from 2015 to 2021.

Methods: A retrospective population-wide observational study in Manitoba, Canada, was conducted using administrative claims data from the Manitoba Centre for Health Policy to examine the incidence and prevalence of OUD (methadone, buprenorphine-naloxone, buprenorphine) or AUD medications (naltrexone, acamprosate, disulfiram) per 10,000 individuals in each quarter between January 1, 2015, and December 31, 2021.

Results: There were 1179 and 451 individuals who received at least one prescription for OUD and AUD, respectively, in the first quarter of 2020.

Exploring Greater Flexibility for Chronic Toxicity Study Designs to Support Human Safety Assessment While Balancing 3Rs Considerations.

Chronic repeated-dose toxicity studies are required to support long-term dosing in late-stage clinical trials, providing data to adequately characterize adverse effects of potential concern for human safety. Different regulatory guidances for the design and duration of chronic toxicity studies are available, with flexibility in approaches often adopted for specific drug modalities. These guidances may provide opportunities to reduce time, cost, compound requirement and animal use within drug development programs if applied more broadly and considered outside their current scopes of use.

Maternal diabetes and fracture risk in offspring: a population-based analysis.

Factors affecting intrauterine environment exerts influence on skeletal health and fracture risk in later life. Diabetes during pregnancy is known to influence birth weight and is associated with fetal overgrowth. However, the effects of maternal diabetes on fracture risk in offspring is unknown.

Incidence and prevalence of type 2 diabetes in Manitoba children 2009-10 to 2017-18: First Nation versus all other Manitobans.

Aim: To describe the incidence and prevalence of type 2 diabetes in children in Manitoba over a ten-year period.

Methods: Population-based, provincial databases were linked to calculate the incidence and prevalence of type 2 diabetes in children < 18 years of age in Manitoba from 2009-10 to 2017-18. First Nation and all other Manitoban children are described separately.

Rate of Total Hip Replacement after Legg Calve Perthes Disease in a Canadian Province.

Legg Calve Perthes disease is a pediatric hip condition that leads to early hip degeneration. The efficacy of operative and nonoperative treatment is not well defined in the literature. Using the rate of total hip arthroplasty as a surrogate measure for symptomatic hip degeneration, the rate of total hip arthroplasty was compared in Legg Calve Perthes disease patients with and without previous surgical intervention in the province of Manitoba, Canada.

A matched-control study on the impact of depressive disorders following lumbar fusion for adult spinal deformity: an analysis of a nationwide administrative database.

Purpose: In recent years, depression rates have been on the rise, resulting in soaring mental health issues globally. There is paucity of literature about the impact of depression on lumbar fusion for adult spine deformity. The purpose of this study is to investigate whether patients with depressive disorders undergoing lumbar deformity fusion have higher rates of (1) in-hospital length of stay; (2) ninety-day medical and surgical complications; and (3) medical reimbursement.

Prescription drug usage as measure of comorbidity resolution after bariatric surgery: a population-based cohort study.

Background: Obesity is a chronic and progressive disease associated with significant morbidity, mortality, and health-care costs. Bariatric surgery is the most effective intervention for sustainable weight loss and resolution of obesity-related comorbidities. Studies examining comorbidity resolution largely rely on individual self-reported outcomes and electronic record reviews.

Comparison of baseline demographics and risk factors for aseptic loosening following primary total elbow arthroplasty.

Background: Aseptic loosening is a feared complication following total elbow arthroplasty (TEA); however, literature regarding factors that may contribute to this complication is limited. The aims of this investigation were to: (1) compare baseline demographics of patients who developed aseptic loosening following primary TEA; and (2) identify patient-specific risk factors for the development of loosening.

Methods: Retrospective analysis using a nationwide claims database was performed to identify patients who underwent primary TEA and developed aseptic loosening within 2 years (study n = 307, control n = 10,741).

Changes in Prevalence and Incidence at the Population Level of Type 2 Diabetes in First Nations and All Other Adults in Manitoba.

Objectives: The prevalence of type 2 diabetes (T2D) is increasing and Indigenous populations are at highest risk. Canadian data are crucial for health planning.

Methods: Population-based, de-identified, linked databases were used to calculate the incidence and prevalence of T2D for registered adult First Nations Manitobans and all other adult Manitobans from 2011-2012 to 2016-2017.

The use of recovery animals in nonclinical safety assessment studies with monoclonal antibodies: further 3Rs opportunities remain.

Assessment of reversibility from nonclinical toxicity findings in animals with potential adverse clinical impact is required during pharmaceutical development, but there is flexibility around how and when this is performed and if recovery animals are necessary. For monoclonal antibodies (mAbs) and in accordance with ICH S6(R1) if inclusion of recovery animals is warranted, this need only occur in one study. Data on study designs for first-in-human (FIH)-enabling and later-development toxicity studies were shared from a recent collaboration between the NC3Rs, EPAA, Netherlands Medicines Evaluation Board (MEB) and 14 pharmaceutical companies.

Re-evaluating the need for chronic toxicity studies with therapeutic monoclonal antibodies, using a weight of evidence approach.

To support registration of monoclonal antibodies (mAbs) for chronic indications, 6-month toxicity studies have historically been conducted. Experience with mAb development has shown a relatively benign and well-understood safety profile for this class, with most toxicity findings anticipated based on pharmacology. We evaluated whether a 6-month toxicity study is necessary to assess the long-term safety of mAbs.

Assessing the migrant mortality advantage among foreign-born and interprovincial migrants in Manitoba, Canada.

Objectives: Studies on mortality differentials between international immigrants and non-immigrants produced mixed results. The mortality of interprovincial migrants has been less studied. Our objectives were to compare mortality risk between international immigrants, interprovincial migrants, and long-term residents of the province of Manitoba, Canada, and identify factors associated with mortality among migrants.

Mental health comorbidity is common in children with type 2 diabetes.

Objective: To describe the prevalence of mental health comorbidity in children with type 2 diabetes compared to a matched population without diabetes and children with type 1 diabetes.

Research Design And Methods: Population-based cohorts of 528 youth (7-18 years of age) with prevalent type 2 diabetes, 1519 matched children without diabetes and 778 youth with type 1 diabetes were identified from a clinical registry and linked to provincial health care records to assess the prevalence of mental health comorbidity using ICD-9CM, ICD-10CA and ATC codes.

Results: The majority of children with type 2 diabetes were of First Nations heritage.

Hospitalization and comorbidity in children with type 2 diabetes.

Objective: To describe hospitalization rates and reasons for hospitalization in children with type 2 diabetes (T2D) and to compare these rates to a matched cohort without diabetes and to children with type 1 diabetes (T1D).

Methods: Population-based cohorts of 528 children (7-18 years of age) with prevalent T2D, 1519 matched control children without diabetes and 778 children with T1D were identified from a clinical registry and linked to health care records to assess hospitalizations and reasons for hospitalizations using ICD-9CM and ICD-10CA codes.

Results: Children with T2D are more likely than their matched controls and children with T1D to be admitted to hospital in the year prior to diagnosis {RR 2.

Pregestational Diabetes Exposure In Utero: Validation of a Definition for Use in Administrative Data.

Objective: Our aim in this study was to determine the best administrative data case definition for pregestational diabetes exposure.

Methods: We compared the performance of case definitions for pregestational diabetes exposure within the administrative health data housed in the Manitoba Population Health Research Repository at the Manitoba Centre for Health Policy with an identified population of women in whom the diagnosis of pregestational diabetes was known from the clinical database of the Manitoba Diabetes Education Resource for Children and Adolescents (DER-CA) (August 12, 1989 through January 28, 2015). The DER-CA database contains maternal diabetes status during pregnancy and also includes women diagnosed with type 2 diabetes in childhood whose pregnancies were thus all complicated by pregestational diabetes exposure.

Exploring the Definition of "Similar Toxicities": Case Studies Illustrating Industry and Regulatory Interpretation of ICH S6(R1) for Long-Term Toxicity Studies in One or Two Species.

ICH S6 (R1) states that safety evaluation of biotherapeutics should normally include 2 relevant species when available (i.e., a rodent and non-rodent species in which the test material is pharmacologically active), at least for short-term toxicology studies (generally supporting Phase I trials).

Cardiovascular disease and the risk of dementia: a survival analysis using administrative data from Manitoba.

Objectives: Recent research has shown that cardiovascular disease (CVD) raises the risk of dementia and other forms of cognitive decline. Generally, these studies are unable to model the time of diagnosis of CVD in their analyses and treat CVD as a time-fixed variable. Our objective was to assess the risk of being diagnosed with dementia for individuals diagnosed with CVD when CVD is time-dependent.

Refining Procedures within Regulatory Toxicology Studies: Improving Animal Welfare and Data.

During the development of potential new medicines or agrochemicals, an assessment of the safety profile to humans and environmental species is conducted using a range of different in silico and in vitro techniques in conjunction with metabolism and toxicity studies using animals. The required studies are outlined within international regulatory guidelines which acknowledge and support the application of the 3Rs to reduce the number of animals used or to refine the procedures performed when these studies are deemed to be necessary. The continued development of new technologies and adoption of best-practice approaches to laboratory animal housing and study procedures has generated a series of refinements that can be incorporated into animal studies throughout the package.

Use of pharmacotherapy for alcohol use disorder in Manitoba, Canada: A whole-population cohort study.

Objective: Update the evidence on use of pharmacotherapy for alcohol use disorder in a Canadian population.

Methods: Using whole-population administrative data from Manitoba, Canada, we identified all residents age 12+ who were first diagnosed with alcohol use disorder between April 1, 1996 and March 31, 2015, and compared characteristics of those who filled a prescription for naltrexone, acamprosate or disulfiram at least once during that period to those who did not fill a prescription for an alcohol use disorder medication.

Results: Only 1.