Characterization of Y chromosome diversity in newfoundland and labrador: evidence for a structured founding population.

The population of Newfoundland and Labrador (NL) is largely derived from settlers who migrated primarily from England and Ireland in the 1700s-1800s. Previously described as an isolated founder population, based on historical and demographic studies, data on the genetic ancestry of this population remains fragmentary. Here we describe the largest investigation of patrilineal ancestry in NL. To determine the paternal genetic structure of the population, 1,110 Y chromosomes from an NL-based cohort were analyzed using 5,761 Y-specific SNPs. We identified 160 distinct terminal haplogroups, the majority of which (71.4%) belong to the R1b haplogroup. When compared with global reference populations, the NL population haplogroup composition and frequencies primarily resemble those observed in English and Irish ancestral source populations. There is also evidence of genetic contributions from Basque, French, Portuguese, and Spanish fishermen and early settlers who frequented NL. Interestingly, the observed population structure shows geographical and religious clustering that can be associated with the settlement of the ancestral source populations from predominantly Protestant, England, and Catholic, Ireland respectively. For example, the R1b-M222 haplogroup, seen in people of Irish descent, is found clustered in the Irish-settled Southeast region of NL. The clustering and expansion of Y haplogroups in conjunction with the geographical and religious clusters illustrate that limited subsequent in-migration, geographic isolation, and societal factors have contributed to the genetic substructure of the NL population and its designation as a founder population.

A 12-Month Follow-Up of the Effects of a Digital Diabetes Prevention Program (VP Transform for Prediabetes) on Weight and Physical Activity Among Adults With Prediabetes: Secondary Analysis.

BACKGROUND: The prevalence of diabetes is increasing rapidly. Previous research has demonstrated the efficacy of a diabetes prevention program (DPP) in lifestyle modifications that can prevent or delay the onset of type 2 diabetes among individuals at risk. Digital DPPs have the potential to use technology, in conjunction with behavior change science, to prevent prediabetes on a national and global scale. OBJECTIVE: The aim of this study is to investigate the effects of a digital DPP (Virgin Pulse [VP] Transform for Prediabetes) on weight and physical activity among participants who had completed 12 months of the program. METHODS: This study was a secondary analysis of retrospective data of adults with prediabetes who were enrolled in VP Transform for Prediabetes for 12 months of the program. The program incorporates interactive mobile computing, remote monitoring, an evidence-based curriculum, behavior tracking tools, health coaching, and online peer support to prevent or delay the onset of type 2 diabetes. RESULTS: The sample (N=1095) was comprised of people with prediabetes who completed at least 9 months of the VP Transform for Prediabetes program. Participants were 67.7% (n=741) female, with a mean age of 53.6 (SD 9.75) years. After 12 months, participants decreased their weight by an average of 10.9 lbs (5.5%; P<.001) and increased their physical activity by 91.2 (P<.001) minutes. CONCLUSIONS: These results suggest that VP Transform for Prediabetes is effective at preventing type 2 diabetes through a significant reduction in body weight and increase of physical activity. Furthermore, these results suggest that the DPP remains effective 12 months after beginning the program. A prospective randomized controlled clinical study is warranted to validate these findings.

Proptosis and Diplopia Response With Teprotumumab and Placebo vs the Recommended Treatment Regimen With Intravenous Methylprednisolone in Moderate to Severe Thyroid Eye Disease: A Meta-analysis and Matching-Adjusted Indirect Comparison.

IMPORTANCE: Thyroid eye disease can be a debilitating autoimmune disorder characterized by progressive proptosis or diplopia. Teprotumumab has been compared with placebo in randomized clinical trials, but not with intravenous methylprednisolone (IVMP), which sometimes is used in clinical practice for this condition. OBJECTIVE: To conduct a matching-adjusted indirect comparison of teprotumumab vs IVMP vs placebo. DATA SOURCES: Deidentified patient-level data from teprotumumab trials and aggregate-level data from literature on the most recommended regimen of IVMP. STUDY SELECTION: PubMed and Embase were searched for randomized/observational studies using key terms and controlled vocabulary. Full texts of eligible articles were reviewed and cataloged. DATA EXTRACTION AND SYNTHESIS: Conducted by 1 reviewer (R.A.Q.) and 1 verifier (R.B.), including study characteristics, eligibility criteria, baseline characteristics, and outcomes. MAIN OUTCOMES AND MEASURES: Changes in proptosis by millimeter and diplopia response (percentage with ≥1 grade reduction) from baseline to week 12 in patients receiving IVMP and placebo, and to week 24 in patients receiving teprotumumab. RESULTS: The search identified 1019 records, and 6 through manual searches, alerts, and secondary references. After excluding duplicates and screening full-text records, 12 IVMP studies were included in the matching-adjusted indirect comparison (11 for proptosis change [n = 419], 4 for diplopia response [n = 125], and 2 teprotumumab [n = 79] and placebo [n = 83] comparator studies). Treatment with IVMP resulted in a proptosis difference of -0.16 mm (95% CI, -1.55 to 1.22 mm) from baseline to week 12 vs placebo. The proptosis treatment difference between IVMP and teprotumumab of -2.31 mm (95% CI, -3.45 to -1.17 mm) favored teprotumumab. Treatment with IVMP (odds ratio, 2.69; 95% CI, 0.94-7.70) was not favored over placebo in odds of diplopia response; however, teprotumumab was favored over IVMP (odds ratio, 2.32; 95% CI, 1.07-5.03). CONCLUSIONS AND RELEVANCE: This meta-analysis suggests that use of IVMP is associated with a small, typically not clinically relevant, change from baseline in proptosis vs placebo, with modest changes in diplopia. While this nonrandomized comparison suggests that use of teprotumumab, compared with IVMP, is associated with greater improvements in proptosis and may be twice as likely to have a 1 grade or higher reduction in diplopia, randomized trials comparing these 2 treatments would be warranted to determine if 1 treatment is superior to the other to a clinically relevant degree.

The effects of recreational cannabis use on glycemic outcomes and self-management behaviours in people with type 1 and type 2 diabetes: a rapid review.

BACKGROUND: Recent surveys of Canadian cannabis users reflect increasing consumption rates, some of whom may have diabetes. However, healthcare providers have limited information resources on the effects of recreational cannabis in people with diabetes. This rapid review was commissioned by Diabetes Canada to synthesize available evidence to guide recommendations for care of people 13 years of age and older who live with diabetes. METHODS: PubMed, Embase and PsycINFO databases were searched from January 2008 to January 2019. Study selection, data abstraction and quality appraisal were completed by pairs of reviewers working independently and discrepancies were resolved by a third reviewer with pilot tests completed before each stage to ensure consistency. Data collected from included studies were tabulated and summarized descriptively. RESULTS: The search resulted in 1848 citations of which 59 publications were selected for screening, resulting in six observational studies (2 full-text articles and 4 conference abstracts) that met the pre-defined criteria for inclusion. Five studies reported higher glycated hemoglobin (HbA1c) in people with type 1 diabetes (T1D) who consumed recreational cannabis. In one study, students aged 17 to 25 years living with T1D self-reported poorer glycemic control and higher HbA1c when smoking cannabis. In one study of adults with T1D, cannabis use within the previous 12 months was associated with almost double the risk of diabetic ketoacidosis compared with no cannabis use (odds ratio [OR] 1.98; confidence interval [CI] [95% CI] 1.01-3.91). Risks for peripheral arterial occlusion and myocardial infarction were found to be higher in people with type 2 diabetes (T2D) who consumed recreational cannabis, and worse renal parameters were also reported in two separate studies of T1D and T2D. CONCLUSIONS: Recreational cannabis use may negatively impact diabetes metabolic factors and self-management behaviours in people with T1D. In people with T2D, recreational cannabis may increase risks for peripheral arterial occlusion, myocardial infarction and renal disease. However, the evidence base of this rapid review was limited to six observational studies of poor to fair methodological quality, and thus, further robust, higher quality research is required to confirm the potential impact of cannabis on diabetes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019122829.