| 101. |
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| 102. |
- Raghavan, Maanasa, et al.
(författare)
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Genomic evidence for the Pleistocene and recent population history of Native Americans
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 349:6250
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Tidskriftsartikel (refereegranskat)abstract
- Howand when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we found that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (ka) and after no more than an 8000-year isolation period in Beringia. After their arrival to the Americas, ancestral Native Americans diversified into two basal genetic branches around 13 ka, one that is now dispersed across North and South America and the other restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians (including Siberians) and, more distantly, Australo-Melanesians. Putative "Paleoamerican" relict populations, including the historical Mexican Pericues and South American Fuego-Patagonians, are not directly related to modern Australo-Melanesians as suggested by the Paleoamerican Model.
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| 103. |
- Singh, Jagmeet P., et al.
(författare)
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Phased target trial design and meta-analysis in a head-to-head treatment comparison
- 2023
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Ingår i: Pharmacoepidemiology and Drug Safety. - : John Wiley & Sons. - 1053-8569 .- 1099-1557. ; 32:Suppl. 1, s. 444-444
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: For conditions with rare clinical outcomes, real-world treatment comparisons are challenging to design and prone to confounding.Objectives: To present a robust methodologic approach for rigorous and transparent assessment of rare outcomes using real-world data.Methods: We emulated a target trial using an active comparator, new-user design to compare dronedarone to sotalol for rhythm control in atrial fibrillation (AF) as both are recommended for similar patient phenotypes. Using one protocol, a pre-specified stepwise approach was implemented across 4 datasets (Optum CDM; IBM MarketScan; Veterans Affairs Electronic Health Records; Swedish National Patient Register). Meta-analysis was used to ensure sufficient capture of specific, rare primary outcomes (cardiovascular (CV) hospitalization and ventricular proarrhythmia) and to evaluate consistency of findings across patient populations. Steps 1–3 focused on cohort selection, propensity score matching (PSM), baseline equipoise and residual confounding assessment via negative control outcome analyses. In steps 4–6, outcomes in the individual cohorts were analyzed using an as-treated approach and Cox proportional hazards models. Step 7 included a heterogeneity assessment, meta-analysis using fixed effects models, and hypothesis testing using a hierarchical approach. In step 8, sensitivity analyses, including E-values and Inverse Probability of Censoring Weighting, were conducted to verify the robustness of findings.Results: In step 1, 35,467 sotalol and 27,955 dronedarone patients with AF who were antiarrhythmic drug-naive were identified across databases. In steps 2–3, 23,275 dronedarone patients were PS-matched to 23,275 sotalol patients. Baseline covariates were well-balanced and little-to-no residual confounding was observed via the negative control analyses. Individual HRs were estimated in steps 4–6, and, when no significant heterogeneity between databases was observed, hazard ratios (HRs) were pooled across datasets in step 7. For example, for CV hospitalization, dronedarone was superior to sotalol with no heterogeneity (HR: 0.91; 95% CI: 0.85, 0.97; Cochran Q p-value: 0.32). Eleven sensitivity analyses were conducted in step 8 and confirmed that findings were generally robust.Conclusions: An active comparator, new-user design using the target trial approach coupled with meta-analysis generated consistent findings across databases and countries using one protocol. Similar methods, including a pre-specified stepwise approach, negative control outcome, and tests for robustness should be considered for real-world studies where specific, rare outcomes need to be examined in a rigorous and transparent way.
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| 104. |
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| 105. |
- Florez, J, et al.
(författare)
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Testing of diabetes-associated WFS1 polymorphisms in the Diabetes Prevention Program
- 2007
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 51:3, s. 451-457
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Wolfram syndrome (diabetes insipidus, diabetes mellitus, optic atrophy and deafness) is caused by mutations in the WFS1 gene. Recently, single nucleotide polymorphisms (SNPs) in WFS1 have been reproducibly associated with type 2 diabetes. We therefore examined the effects of these variants on diabetes incidence and response to interventions in the Diabetes Prevention Program (DPP), in which a lifestyle intervention or metformin treatment was compared with placebo.Methods: We genotyped the WFS1 SNPs rs10010131, rs752854 and rs734312 (H611R) in 3,548 DPP participants and performed Cox regression analysis using genotype, intervention and their interactions as predictors of diabetes incidence. We also evaluated the effect of these SNPs on insulin resistance and beta cell function at 1 year.Results: Although none of the three SNPs was associated with diabetes incidence in the overall cohort, white homozygotes for the previously reported protective alleles appeared less likely to develop diabetes in the lifestyle arm. Examination of the publicly available Diabetes Genetics Initiative genome-wide association dataset revealed that rs10012946, which is in strong linkage disequilibrium with the three WFS1 SNPs (r 2 = 0.88–1.0), was associated with type 2 diabetes (allelic odds ratio 0.85, 95% CI 0.75–0.97, p = 0.026). In the DPP, we noted a trend towards increased insulin secretion in carriers of the protective variants, although for most SNPs this was seen as compensatory for the diminished insulin sensitivity.Conclusions/interpretation: The previously reported protective effect of select WFS1 alleles may be magnified by a lifestyle intervention. These variants appear to confer an improvement in beta cell function.
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| 106. |
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| 107. |
- Freedman, Ben, et al.
(författare)
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Screening for Atrial Fibrillation A Report of the AF-SCREEN International Collaboration
- 2017
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Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 135:19, s. 1851-
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Tidskriftsartikel (refereegranskat)abstract
- Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed in September 2015 to promote discussion and research about AF screening as a strategy to reduce stroke and death and to provide advocacy for implementation of country-specific AF screening programs. During 2016, 60 expert members of AF-SCREEN, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare sections of a draft document. In August 2016, 51 members met in Rome to discuss the draft document and consider the key points arising from it using a Delphi process. These key points emphasize that screen-detected AF found at a single timepoint or by intermittent ECG recordings over 2 weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. With regard to the methods of mass screening, handheld ECG devices have the advantage of providing a verifiable ECG trace that guidelines require for AF diagnosis and would therefore be preferred as screening tools. Certain patient groups, such as those with recent embolic stroke of uncertain source (ESUS), require more intensive monitoring for AF. Settings for screening include various venues in both the community and the clinic, but they must be linked to a pathway for appropriate diagnosis and management for screening to be effective. It is recognized that health resources vary widely between countries and health systems, so the setting for AF screening should be both country-and health system-specific. Based on current knowledge, this white paper provides a strong case for AF screening now while recognizing that large randomized outcomes studies would be helpful to strengthen the evidence base.
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| 108. |
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| 109. |
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| 110. |
- Mungovan, S. F., et al.
(författare)
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Preoperative exercise interventions to optimize continence outcomes following radical prostatectomy
- 2021
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Ingår i: Nature Reviews Urology. - : Springer Science and Business Media LLC. - 1759-4812 .- 1759-4820. ; 18, s. 259-81
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Tidskriftsartikel (refereegranskat)abstract
- Incontinence is a common complication of radical prostatectomy and can have a considerable effect on quality of life for men who have survived prostate cancer. In the past, management of postoperative incontinence has focused on rehabilitation and postsurgical management, but prehabilitation, in the form of pelvic floor muscle exercises and training, has the potential to improve postprostatectomy continence outcomes, provide patients with agency for their own health and improve quality of life in men who have been treated for prostate cancer. Urinary incontinence is a common and predictable consequence among men with localized prostate cancer who have undergone radical prostatectomy. Despite advances in the surgical technique, urinary continence recovery time remains variable. A range of surgical and patient-related risk factors contributing to urinary incontinence after radical prostatectomy have been described, including age, BMI, membranous urethral length and urethral sphincter insufficiency. Physical activity interventions incorporating aerobic exercise, resistance training and pelvic floor muscle training programmes can positively influence the return to continence in men after radical prostatectomy. Traditional approaches to improving urinary continence after radical prostatectomy have typically focused on interventions delivered during the postoperative period (rehabilitation). However, the limited efficacy of these postoperative approaches has led to a shift from the traditional reactive model of care to more comprehensive interventions incorporating exercise-based programmes that begin in the preoperative period (prehabilitation) and continue after surgery. Comprehensive prehabilitation interventions include appropriately prescribed aerobic exercise, resistance training and specific pelvic floor muscle instruction and exercise training programmes. Transperineal ultrasonography is a non-invasive and validated method for the visualization of the action of the pelvic floor musculature, providing real-time visual biofeedback to the patient during specific pelvic floor muscle instruction and training. Importantly, the waiting time before surgery can be used for the delivery of comprehensive prehabilitation exercise-based interventions to increase patient preparedness in the lead-up to surgery and optimize continence and health-related quality-of-life outcomes following radical prostatectomy.
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