Medicine

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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty

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    Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci
    (Frontiers Research Foundation, 2023) de Las, F.L.; Schwande, K.L.; Brown, M.R.; Bentley, A.R.; Winkler, T.W.; Sung, Y.J.; Munroe, P.B.; Miller, C.L.; Aschard, H.; Aslibekyan, S.; Bartz, T.M.; Bielak, L.F.; Chai, J.F.; Cheng, C.Y.; Dorajoo, R.; Feitosa, M.F.; Guo, X.; Hartwig, F.P.; Horimoto, A.; Kolčić, I.; Lim, E.; Liu, Y.; Manning, A.K.; Marten, J.; Musani, S.K.; Noordam, R.; Padmanabhan, S.; Rankinen, T.; Richard, M.A.; Ridker, P.M.; Smith, A.V.; Vojinovic, D.; Zonderman, A.B.; Alver, M.; Boissel, M.; Christensen, K.; Freedman, B.I.; Gao, C.; Giulianini, F.; Harris, S.E.; He, M.; Hsu, F.C.; Kühnel, B.; Laguzzi, F.; Li, X.; Lyytikäinen, L.P.; Nolte, I.M.; Poveda, A.; Rauramaa, R.; Riaz, M.; Robino, A.; Sofer, T.; Takeuchi, F.; Tayo, B.O.; van der, M.P.J.; Verweij, N.; Ware, E.B.; Weiss, S.; Wen, W.; Yanek, L.R.; Zhan, Y.; Amin, N.; Arking, D.E.; Ballantyne, C.; Boerwinkle, E.; Brody, J.A.; Broeckel, U.; Campbell, A.; Canouil, M.; Chai, X.; Chen, Y.I.; Chen, X.; Chitrala, K.N.; Concas, M.P.; de Faire, U.; de Mutsert, R.; de Silva, H.J.; de Vries, P.S.; Do, A.; Faul, J.D.; Fisher, V.; Floyd, J.S.; Forrester, T.; Friedlander, Y.; Girotto, G.; Gu, C.C.; Hallmans, G.; Heikkinen, S.; Heng, C.K.; Homuth, G.; Hunt, S.; Ikram, M.A.; Jacobs, D.R.J.R.; Kavousi, M.; Khor, C.C.; Kilpeläinen, T.O.; Koh, W.P.; Komulainen, P.; Langefeld, C.D.; Liang, J.; Liu, K.; Liu, J.; Lohman, K.; Mägi, R.; Manichaikul, A.W.; McKenzie, C.A.; Meitinger, T.; Milaneschi, Y.; Nauck, M.; Nelson, C.P.; O'Connell, J.R.; Palmer, N.D.; Pereira, A.C.; Perls, T.; Peters, A.; Polašek, O.; Raitakari, O.T.; Rice, K.; Rice, T.K.; Rich, S.S.; Sabanayagam, C.; Schreiner, P.J.; Shu, X.; Sidney, S.; Sims, M.; Smith, J.A.; Starr, J.M.; Strauch, K.; Tai, E.S.; Taylor, K.D.; Tsai, M.Y.; Uitterlinden, A.G.; Heemst, D.V.; Waldenberger, M.; Wang, Y.; Wei, W.; Wilson, G.; Xuan, D.; Yao, J.; Yu, C.; Yuan, J.; Zhao, W.; Becker, D.M.; Bonnefond, A.; Bowden, D.W.; Cooper, R.S.; Deary, I.J.; Divers, J.; Esko, T.; Franks, P.W.; Froguel, P.; Gieger, C.; Jonas, J.B.; Kato, N.; Lakka, T.A.; Leander, K.; Lehtimäki, T.; Magnusson, P.K.E.; North, K.E.; Ntalla, I.; Penninx, B.; Samani, N.J.; Snieder, H.; Spedicati, B.; Harst, P.V.D.; Völzke, H.; Wagenknecht, L.E.; Weir, D.R.; Wojczynski, M.K.; Wu, T.; Zheng, W.; Zhu, X.; Bouchard, C.; Chasman, D.I.; Evans, M.K.; Fox, E.R.; Gudnason, V.; Hayward, C.; Horta, B.L.; Kardia, S.L.R.; Krieger, J.E.; Mook-Kanamori, D.O.; Peyser, P.A.; Province, M.M.; Psaty, B.M.; Rudan, I.; Sim, X.; Smith, B.H.; Dam, R.M.V.; Duijn, C.M.V.; Wong, T.Y.; Arnett, D.K.; Rao, D.C.; Gauderman, J.; Liu, C.; Morrison, A.C.; Rotter, J.I.; Fornage, M.
    INTRODUCTION: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes. METHODS: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: "Some College" (yes/no, for any education beyond high school) and "Graduated College" (yes/no, for completing a 4-year college degree). Genome-wide significant (p < 5 × 10-8) and suggestive (p < 1 × 10-6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals). RESULTS: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue. DISCUSSION: Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects.
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    Efficacy and safety of low-dose triple and quadruple combination pills vs monotherapy, usual care, or placebo for the initial management of hypertension: A systematic review and meta-analysis
    (American Medical Association, 2023) Wang, N.; Rueter, P.; Atkins, E.; Webster, R.; Huffman, M.; de Silva, A.; Chow, C.; Patel, A.; Rodgers, A.
    IMPORTANCE: Low-dose combination (LDC) antihypertensives consisting of 3 or 4 blood pressure (BP)-lowering drugs have emerged as a potentially important therapy for the initial management of hypertension. OBJECTIVE: To assess the efficacy and safety of LDC therapies for the management of hypertension. DATA SOURCES: PubMed and Medline were searched from date of inception until September 2022. STUDY SELECTION: Randomized clinical trials comparing LDC consisting of 3 or 4 BP-lowering drugs compared to either monotherapy, usual care, or placebo. DATA EXTRACTION AND SYNTHESIS: Data were extracted by 2 independent authors and synthesized using both random and fixed-effects models using risk ratios (RR) for binary outcomes and mean differences for continuous outcomes. MAIN OUTCOMES AND MEASURES: The primary outcome was mean reduction in systolic BP (SBP) between LDC and monotherapy, usual care, or placebo. Other outcomes of interest included the proportion of patients achieving BP less than 140/90 mm Hg, rates of adverse effects, and treatment withdrawal. RESULTS: Seven trials with a total of 1918 patients (mean [mean range] age, 59 [50-70] years; 739 [38%] female) were included. Four trials involved triple-component LDC and 3 involved quadruple-component LDC. At 4 to 12 weeks follow-up, LDC was associated with a greater mean reduction in SBP than initial monotherapy or usual care (mean reduction, 7.4 mm Hg; 95% CI, 4.3-10.5) and placebo (mean reduction, 18.0 mm Hg; 95% CI, 15.1-20.8). LDC was associated with a higher proportion of participants achieving BP less than 140/90 mm Hg at 4 to 12 weeks compared to both monotherapy or usual care (66% vs 46%; RR, 1.40; 95% CI, 1.27-1.52) and placebo (54% vs 18%; RR, 3.03; 95% CI, 1.93-4.77). There was no significant heterogeneity between trials enrolling patients with and without baseline BP-lowering therapy. Results from 2 trials indicated LDC remained superior to monotherapy or usual care at 6 to 12 months. LDC was associated with more dizziness (14% vs 11%; RR 1.28, 95% CI 1.00-1.63) but no other adverse effects nor treatment withdrawal. CONCLUSIONS AND RELEVANCE: The findings in the study showed that LDCs with 3 or 4 antihypertensives were an effective and well-tolerated BP-lowering treatment option for the initial or early management of hypertension.
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    Prevalence of suicidal behaviour among students living in Muslim-majority countries: systematic review and meta-analysis
    (Royal College of Psychiatrists, 2023) Arafat, S.M.Y.; Baminiwatta, A.; Menon, V.; Singh, R.; Varadharajan, N.; Guhathakurta, S.; Mahesar, R.A.; Rezaeian, M.
    BACKGROUND: Assessing suicidal behaviours among students would help to understand the burden and enhance suicide prevention. AIMS: We aimed to determine the prevalence of suicidal behaviour among students living in Muslim-majority countries. METHOD: We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic search was conducted in Medline, EMBASE and PsycINFO. Meta-analyses were performed to pool the lifetime, 1-year and point prevalence rates for suicidal ideation, plans and attempts. RESULTS: From 80 studies, 98 separate samples were included in this analysis. The majority (n = 49) were from the Eastern Mediterranean, and 61 samples were of university students. The pooled prevalence of suicidal ideation was 21.9% (95% CI 17.4%-27.1%) for lifetime, 13.4% (95% CI 11.1%-16.1%) for the past year and 6.4% (95% CI 4.5%-9%) for current. The pooled prevalence of suicide plans was 6.4% (95% CI 3.7%-11%) for lifetime, 10.7% (95% CI 9.1%-12.4%) for the past year and 4.1% (95% CI 2.7%-6.2%) for current. The pooled prevalence of suicide attempts was 6.6% (95% CI 5.4%-8%) for lifetime and 4.9% (95% CI 3.6%-6.5%) for the past year. The lifetime prevalence of suicidal ideation was highest (46.2%) in South-East Asia, but the 12-month prevalence was highest (16.8%) in the Eastern Mediterranean. CONCLUSIONS: The study revealed notably high rates of suicidal behaviours among students living in Muslim-majority countries. However, the quality of studies, differences in regional and cultural factors, stages of studentship and methods of measurement should be considered when generalising the study results.
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