Medicine
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Item Unveiling the intricacies: Insight into gastroesophageal reflux disease(Baishideng Publishing Group, 2025-01) Wickramasinghe, N.; Devanarayana, N. M.Gastroesophageal reflux disease (GERD) poses a substantial global health challenge, with prevalence rates exhibiting geographical variation. Despite its widespread recognition, the exact prevalence and associated risk factors remain elusive. This article comprehensively analyzed the global burden of GERD, shedding light on its risk factors, underlying pathophysiological mechanisms, current diagnostic modalities, evolving management strategies tailored to diverse patient profiles, and complex determinants contributing to treatment failures. A deeper comprehension of GERD is achieved by dissecting these intricate facets, paving the way for enhanced clinical management and improved patient outcomes.Item Nature, prevalence and determinants of mental health problems experienced by adolescents in south Asia: a systematic review(Elsevier Ltd, 2025-01) Mudunna, C.; Weerasinghe, M.; Tran, T.; Antoniades, J.; Romero, L.; Chandradasa, M.; Fisher, J.BACKGROUND Adolescence is a sensitive phase of human development where individuals, aged 10-19 years, are particularly vulnerable to developing mental health problems (MHPs). South Asia, home to 24% of the world's population, is mostly comprised of low- and middle-income countries (LMIC). Most of the world's young people live in LMICs. This systematic review aims to assess the available evidence on the nature, prevalence and determinants of MHPs experienced by adolescents in south Asia. METHODS Following PRISMA guidelines, searches were conducted in four online databases (Ovid Medline, Ovid EMBASE, Ovid Global Health, Ovid PsycInfo), titles, abstracts, and full-texts were screened, data extracted and quality assessed. Extracted data were categorised into school-based studies (SBS) and non-school-based studies (NSBS). Data were further stratified according to country, MHPs and narratively synthesised. FINDINGS Of the 5847 records identified in the searches, 117 met inclusion criteria. Most (n = 87) were SBS. Key MHPs reported across countries include anxiety disorders and depression. Wide ranges of prevalence rates were reported for anxiety in Indian SBS (1.5-81.6%) and NSBS (1.8-88.1%), and for depression, Pakistani SBS (21-79%) and Indian NSBS (0.4-98.5%). Determinants include individual characteristics; violent victimisation; poor family/home/school environment/peer relationships; already experiencing MHPs and substance use/abuse. Increased physical activity, adequate nutrition, safe/positive homes/family environment, being unmarried females, higher maternal education, peer support/friendship, higher education level and engaging in extra-curricular activities were protective of mental well-being. INTERPRETATION Prevalence of MHPs among south Asian adolescents appears high. Determinants include social, cultural, environmental and socioeconomic factors often beyond individual control. Mental health policies and programs and research appropriate to the cultural context, that address social determinants of MHPs and evidence gaps, are needed to tackle the significant mental health burden among south Asian adolescents. FUNDING Authors CM and MW are supported by a Monash University Research Training Program Scholarship. JF is supported by the Finkel Professorial Fellowship funded by the Finkel Family Foundation.Item Global, regional, and national age-sex-specific burden of diarrhoeal diseases, their risk factors, and aetiologies, 1990-2021, for 204 countries and territories: a systematic analysis for the Global Burden of Disease Study 2021(Elsevier Science, 2024-12) Mettananda, S. (GBD 2021 Diarrhoeal Diseases Collaborators)BACKGROUND Diarrhoeal diseases claim more than 1 million lives annually and are a leading cause of death in children younger than 5 years. Comprehensive global estimates of the diarrhoeal disease burden for specific age groups of children younger than 5 years are scarce, and the burden in children older than 5 years and in adults is also understudied. We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 to assess the burden of, and trends in, diarrhoeal diseases overall and attributable to 13 pathogens, as well as the contributions of associated risk factors, in children and adults in 204 countries and territories from 1990 to 2021.METHODS We used the Cause of Death Ensemble modelling strategy to analyse vital registration data, verbal autopsy data, mortality surveillance data, and minimally invasive tissue sampling data. We used DisMod-MR (version 2.1), a Bayesian meta-regression tool, to analyse incidence and prevalence data identified via systematic reviews, population-based surveys, and claims and inpatient data. We calculated diarrhoeal disability-adjusted life-years (DALYs) as the sum of years of life lost (YLLs) and years lived with disability (YLDs) for each location, year, and age-sex group. For aetiology estimation, we used a counterfactual approach to quantify population-attributable fractions (PAFs). Additionally, we estimated the diarrhoeal disease burden attributable to the independent effects of risk factors using the comparative risk assessment framework.FINDINGS In 2021, diarrhoeal diseases caused an estimated 1·17 million (95% uncertainty interval 0·793-1·62) deaths globally, representing a 60·3% (50·6-69·0) decrease since 1990 (2·93 million [2·31-3·73] deaths). The most pronounced decline was in children younger than 5 years, with a 79·2% (72·4-84·6) decrease in diarrhoeal deaths. Global YLLs also decreased substantially, from 186 million (147-221) in 1990 to 51·4 million (39·9-65·9) in 2021. In 2021, an estimated 59·0 million (47·2-73·2) DALYs were attributable to diarrhoeal diseases globally, with 30·9 million (23·1-42·0) of these affecting children younger than 5 years. Leading risk factors for diarrhoeal DALYs included low birthweight and short gestation in the neonatal age groups, child growth failure in children aged between 1-5 months and 2-4 years, and unsafe water and poor sanitation in older children and adults. We estimated that the removal of all evaluated diarrhoeal risk factors would reduce global DALYs from 59·0 million (47·2-73·2) to 4·99 million (1·99-10·0) among all ages combined. Globally in 2021, rotavirus was the predominant cause of diarrhoeal deaths across all ages, with a PAF of 15·2% (11·4-20·1), followed by norovirus at 10·6% (2·3-17·0) and Cryptosporidium spp at 10·2% (7·03-14·3). In children younger than 5 years, the fatal PAF of rotavirus was 35·2% (28·7-43·0), followed by Shigella spp at 24·0% (15·2-37·9) and adenovirus at 23·8% (14·8-36·3). Other pathogens with a fatal PAF greater than 10% in children younger than 5 years included Cryptosporidium spp, typical enteropathogenicEscherichia coli, and enterotoxigenic E coli producing heat-stable toxin.INTERPRETATION The substantial decline in the global burden of diarrhoeal diseases since 1990, particularly in children younger than 5 years, supports the effectiveness of health interventions such as oral rehydration therapy, enhanced water, sanitation, and hygiene (WASH) infrastructure, and the introduction and scale-up of rotavirus vaccination. Targeted interventions and preventive measures against key risk factors and pathogens could further reduce this burden. Continued investment in the development and distribution of vaccines for leading pathogens remains crucial.Item Undetected falls among older adults attending medical clinics in four tertiary care centres in Sri Lanka; the need of a comprehensive geriatric assessment(BioMed Central, 2024-10) De Zoysa, W.; Rathnayake, N.; Palangasinghe, D.; Silva, S.; Jayasekera, P.; Mettananda, C.; Abeygunasekara, T.; Lekamwasam. S.OBJECTIVE Falls take a high priority among the prevalent medical conditions in old age. Despite this, a history of falls or the risk of future falls is not routinely assessed or properly managed in medical clinics in Sri Lanka. This study was done to evaluate the prevalence and factors associated with falls and recurrent falls among older adults attending medical clinics in four selected tertiary care centres in the country.METHODS A cross-sectional study was carried out at four centres (Teaching Hospital Karapitiya, Colombo South Teaching Hospital, Colombo North Teaching Hospital and University Hospital-Kotelawala Defence University) with 704 older adults, aged 65 years and above, attending medical clinics for more than six consecutive months. Information related to falls and possible associated factors (socio-demographic, behavioural, environmental and biological) were collected using an interviewer-administered questionnaire.Results: The Mean (SD) age of the participants was 72.5(5.5) years and 58.7% were females. Of the 704 total sample, 220 (31.3%, 95% CI 28-35%) participants experienced at least one fall after the age of 65, and 12.8% (95% CI 10-15%) (n = 90) experienced recurrent falls (two or more falls within the last 12 months). Falls were associated with gender, level of education, marital status, and physical dependence (p < 0.01). For those who had at least one fall, multiple logistic regression (MLR) revealed being single (p = 0.03, OR = 2.12, 95% CI; 1.052-4.304), being widowed/divorced/separated (p = 0.03, OR = 1.47, 95% CI; 1.039-2.093) compared to living with a spouse, presence of moderate (p = 0.007, OR = 1.72, 95% CI; 1.160-2.577) and severe (p = 0.001, OR = 2.98, 95% CI; 1.563-5.688) physical dependency compared to mild physical dependency as risk factors for falls. Having secondary education (p = 0.01, OR = 0.55, 0.350-0.876) was a protective factor for falls. For those with recurrent falls, MLR showed moderate physical dependency (p = 0.001, OR = 2.34, 95% CI; 1.442-3.821) compared to slight physical dependency as a risk factor.CONCLUSIONS Approximately one-third of the older adults attending medical clinics had experienced at least a single fall, and one-eighth have had recurrent falls, which were mostly unrecorded and not clinically assessed. Physical dependency was the major contributing factor to falls and recurrent falls. Falls assessment should be included in the routine clinical assessment of older adults attending outdoor medical clinics. Health professionals should be educated to detect and assess those at risk of falling and take appropriate measures to prevent or minimize falls.Item Risk factors for low resilience among grade 10 adolescents in the Gampaha District(Sri Lanka Medical Association, 2023) Manori, D.M.S.; Jayawardana, P.L.; Godamunne, P.INTRODUCTION: Resilience denotes the ability to withstand adversity and bounce back from difficult life events. OBJECTIVE: To determine risk factors for low resilience among Grade 10 adolescents in the District of Gampaha. METHODS: A case-control study with a computed sample size of 128 in each among cases (low resilience) and controls (high resilience) was conducted. Cases and controls were selected by applying simple random sampling to a descriptive study where the magnitude of resilience was determined. For data analysis bivariate (using chi-square test) followed by multiple logistic regression were applied. Results were expressed as adjusted odds ratios with 95% confidence intervals. RESULTS: Risk factors for low resilience were: one or both parents dead (AOR=3.4; 95% CI [1.1, 10.1]; p=0.031), mother’s educational level ≤GCE A/L (AOR=2.3; 95% CI [1.4, 3.6]; p=0.001), losing temper frequently (AOR=2.5; 95% CI [1.9, 3.4]; p<0.001), having <6 friends (AOR=1.4; 95% CI [1.03;1.9]; p<0.048), having <6 close friends (AOR=1.6; 95% CI [1.06, 2.5]; p=0.024), having conflicts with friends (AOR=2.0; 95% CI [1.03, 3.74]; p=0.040), lack of support from home (AOR=1.5; 95% CI [1.04, 2.20]; p=0.031), not seeking help when facing difficult situations (AOR=1.7; 95% CI [1.2, 2.3]; p=0.001), sleeping for <8 hours/day (AOR=1.4; 95% CI [1.2, 1.8]; p=0.007), lack of religious affiliations (AOR=2.6; 95% CI [1.2, 5.7]; p < 0.015) and non-attending Sunday school (AOR=2.1; 95% CI [1.5, 3.2]; p<0.001). CONCLUSION: Eleven risk factors were identified. Recommend conducting cognitive behavioural therapy-based interventions regularly at the school level targeting to minimize the impact of the above risk factors.Item The incidence and risk factors of postpartum diabetes in women from Bangladesh, India and Sri Lanka (South Asia) with prior gestational diabetes mellitus: Results from the LIVING study(Elsevier, 2023) Gupta, Y.; Kapoor, D.; Lakshmi, J.K.; Praveen, D.; Santos, J.A.; Billot, L.; Naheed, A.; de Silva, H.A.; Gupta, I.; Farzana, N.; John, R.; Ajanthan, S.; Bhatla, N.; Desai, A.; Pathmeswaran, A.; Prabhakaran, D.; Teede, H.; Zoungas, S.; Patel, A.; Tandon, N.; LIVING Collaborative GroupAIM: To study, the incidence and risk factors for postpartum diabetes (DM), in women with gestational diabetes mellitus (GDM) from South Asia (Bangladesh, India and Sri Lanka), followed for nearly two years after delivery. METHODS: Women with prior GDM diagnosed using IADPSG criteria were invited at 19 centres across Bangladesh, India and Sri Lanka for an oral glucose tolerance test (OGTT) following childbirth, and were enrolled in a randomized controlled trial. The glycaemic category (outcome) was defined from an OGTT based on American Diabetes Association criteria. RESULTS: Participants (n = 1808) recruited had a mean ± SD age of 31.0 ± 5.0 years. Incident DM was identified, between childbirth and the last follow-up, in 310 (17.1 %) women [incidence 10.75/100 person years], with a median follow-up duration of 1.82 years after childbirth. Higher age, lower education status, higher prior pregnancy count, prior history of GDM, family history of DM, and postpartum overweight/obese status were significantly associated with incident DM. Women in Bangladesh had a higher cumulative incidence of DM [16.49/100 person years] than in Sri Lanka [12.74/100 person years] and India [7.21/100 person years]. CONCLUSIONS: A high incidence of DM was found in women with prior GDM in South Asia, with significant variation between countries. Women from Bangladesh had a significantly higher pregnancy count, family history of DM and overweight/obese status, despite having significantly lower age, which could be responsible for their higher rates of DM. Registration of this study: The study was registered with the Clinical Trials Registry of India (CTRI/2017/06/008744), Sri Lanka Clinical Trials Registry (SLCTR/2017/001), and ClinicalTrials.gov (NCT03305939).Item Patterns of change of multisite pain over one year of follow-up and related risk factors(Philadelphia : Saunders, London, 2022) Ntani, G.; Coggon, D.; Felli, V.E.; Harari, F.; Barrero, L.H.; Felknor, S.A.; Rojas, M.; Serra, C.; Bonzini, M.; Merisalu, E.; Habib, R.R.; Sadeghian, F.; Wickremasinghe, A.R.; Matsudaira, K.; Nyantumbu-Mkhize, B.; Kelsall, H.L.; Harcombe, H.; Walker-Bone, K.Background: Multisite musculoskeletal pain is common and disabling. This study aimed to prospectively investigate distribution of musculoskeletal pain anatomically, and explore risk factors for increases/reductions in the number of painful sites. Methods: Using data from participants working in 45 occupational groups in 18 countries, we explored changes in reporting pain at 10 anatomical sites on two occasions 14 months apart. We used descriptive statistics to explore consistency over time in the number of painful sites, and their anatomical distribution. Baseline risk factors for increases/reductions by ≥3 painful sites were explored by random intercept logistic regression that adjusted for baseline number of painful sites. Results: Amongst 8,927 workers, only 20% reported no pain at either time point, and 16% reported ≥3 painful sites both times. After 14 months, the anatomical distribution of pain often changed but there was only an average increase of 0.17 painful sites. Some 14% workers reported a change in painful sites by ≥ 3. Risk factors for an increase of ≥ 3 painful sites included female sex, lower educational attainment, having a physically demanding job, and adverse beliefs about the work-relatedness of musculoskeletal pain. Also predictive were: older age, somatising tendency, and poorer mental health (each of which was also associated with lower odds of reductions of ≥ 3 painful sites). Conclusions: Longitudinally, the number of reported painful sites was relatively stable but the anatomical distribution varied considerably. These findings suggest an important role for central pain sensitisation mechanisms, rather than localised risk factors, among working adults.Item The power of genetic diversity in genome-wide association studies of lipids(Macmillan Journals Ltd, 2021) Graham, S.E.; Clarke, S.L.; Wu, K.H.; Kanoni, S.; Zajac, G.J.M.; Ramdas, S.; Surakka, I.; Ntalla, I.; Vedantam, S.; Winkler, T.W.; Locke, A.E.; Marouli, E.; Hwang, M.Y.; Han, S.; Narita, A.; Choudhury, A.; Bentley, A.R.; Ekoru, K.; Verma, A.; Trivedi, B.; Martin, H.C.; Hunt, K.A.; Hui, Q.; Klarin, D.; Zhu, X.; Thorleifsson, G.; Helgadottir, A.; Gudbjartsson, D.F.; Holm, H.; Olafsson, I.; Akiyama, M.; Sakaue, S.; Terao, C.; Kanai, M.; Zhou, W.; Brumpton, B.M.; Rasheed, H.; Ruotsalainen, S.E.; Havulinna, A.S.; Veturi, Y.; Feng, Q.; Rosenthal, E.A.; Lingren, T.; Pacheco, J.A.; Pendergrass, S.A.; Haessler, J.; Giulianini, F.; Bradford, Y.; Miller, J.E.; Campbell, A.; Lin, K.; Millwood, I.Y.; Hindy, G.; Rasheed, A.; Faul, J.D.; Zhao, W.; Weir, D.R.; Turman, C.; Huang, H.; Graff, M.; Mahajan, A.; Brown, M.R.; Zhang, W.; Yu, K.; Schmidt, E.M.; Pandit, A.; Gustafsson, S.; Yin, X.; Luan, J.; Zhao, J.H.; Matsuda, F.; Jang, H.M.; Yoon, K.; Medina-Gomez, C.; Pitsillides, A.; Hottenga, J.J.; Willemsen, G.; Wood, A.R.; Ji, Y.; Gao, Z.; Haworth, S.; Mitchell, R.E.; Chai, J.F.; Aadahl, M.; Yao, J.; Manichaikul, A.; Warren, H.R.; Ramirez, J.; Bork-Jensen, J.; Kårhus, L.L.; Goel, A.; Sabater-Lleal, M.; Noordam, R.; Sidore, C.; Fiorillo, E.; McDaid, A.F.; Marques-Vidal, P.; Wielscher, M.; Trompet, S.; Sattar, N.; Møllehave, L.T.; Thuesen, B.H.; Munz, M.; Zeng, L.; Huang, J.; Yang, B.; Poveda, A.; Kurbasic, A.; Lamina, C.; Forer, L.; Scholz, M.; Galesloot, T.E.; Bradfield, J.P.; Daw, E.W.; Zmuda, J.M.; Mitchell, J.S.; Fuchsberger, C.; Christensen, H.; Brody, J.A.; Feitosa, M.F.; Wojczynski, M.K.; Preuss, M.; Mangino, M.; Christofidou, P.; Verweij, N.; Benjamins, J.W.; Engmann, J.; Kember, R.L.; Slieker, R.C.; Lo, K.S.; Zilhao, N.R.; Le, P.; Kleber, M.E.; Delgado, G.E.; Huo, S.; Ikeda, D.D.; Iha, H.; Yang, J.; Liu, J.; Leonard, H.L.; Marten, J.; Schmidt, B.; Arendt, M.; Smyth, L.J.; Cañadas-Garre, M.; Wang, C.; Nakatochi, M.; Wong, A.; Hutri-Kähönen, N.; Sim, X.; Xia, R.; Huerta-Chagoya, A.; Fernandez-Lopez, J.C.; Lyssenko, V.; Ahmed, M.; Jackson, A.U.; Irvin, M.R.; Oldmeadow, C.; Kim, H.N.; Ryu, S.; Timmers, P.R.H.J.; Arbeeva, L.; Dorajoo, R.; Lange, L.A.; Chai, X.; Prasad, G.; Lorés-Motta, L.; Pauper, M.; Long, J.; Li, X.; Theusch, E.; Takeuchi, F.; Spracklen, C.N.; Loukola, A.; Bollepalli, S.; Warner, S.C.; Wang, Y.X.; Wei, W.B.; Nutile, T.; Ruggiero, D.; Sung, Y.J.; Hung, Y.J.; Chen, S.; Liu, F.; Yang, J.; Kentistou, K.A.; Gorski, M.; Brumat, M.; Meidtner, K.; Bielak, L.F.; Smith, J.A.; Hebbar, P.; Farmaki, A.E.; Hofer, E.; Lin, M.; Xue, C.; Zhang, J.; Concas, M.P.; Vaccargiu, S.; van der Most, P.J.; Pitkänen, N.; Cade, B.E.; Lee, J.; van der Laan, S.W.; Chitrala, K.N.; Weiss, S.; Zimmermann, M.E.; Lee, J.Y.; Choi, H.S.; Nethander, M.; Freitag-Wolf, S.; Southam, L.; Rayner, N.W.; Wang, C.A.; Lin, S.Y.; Wang, J.S.; Couture, C.; Lyytikäinen, L.P.; Nikus, K.; Cuellar-Partida, G.; Vestergaard, H.; Hildalgo, B.; Giannakopoulou, O.; Cai, Q.; Obura, M.O.; van Setten, J.; Li, X.; Schwander, K.; Terzikhan, N.; Shin, J.H.; Jackson, R.D.; Reiner, A.P.; Martin, L.W.; Chen, Z.; Li, L.; Highland, H.M.; Young, K.L.; Kawaguchi, T.; Thiery, J.; Bis, J.C.; Nadkarni, G.N.; Launer, L.J.; Li, H.; Nalls, M.A.; Raitakari, O.T.; Ichihara, S.; Wild, S.H.; Nelson, C.P.; Campbell, H.; Jäger, S.; Nabika, T.; Al-Mulla, F.; Niinikoski, H.; Braund, P.S.; Kolcic, I.; Kovacs, P.; Giardoglou, T.; Katsuya, T.; Bhatti, K.F.; de Kleijn, D.; de Borst, G.J.; Kim, E.K.; Adams, H.H.H.; Ikram, M.A.; Zhu, X.; Asselbergs, F.W.; Kraaijeveld, A.O.; Beulens, J.W.J.; Shu, X.O.; Rallidis, L.S.; Pedersen, O.; Hansen, T.; Mitchell, P.; Hewitt, A.W.; Kähönen, M.; Pérusse, L.; Bouchard, C.; Tönjes, A.; Chen, Y.I.; Pennell, C.E.; Mori, T.A.; Lieb, W.; Franke, A.; Ohlsson, C.; Mellström, D.; Cho, Y.S.; Lee, H.; Yuan, J.M.; Koh, W.P.; Rhee, S.Y.; Woo, J.T.; Heid, I.M.; Stark, K.J.; Völzke, H.; Homuth, G.; Evans, M.K.; Zonderman, A.B.; Polasek, O.; Pasterkamp, G.; Hoefer, I.E.; Redline, S.; Pahkala, K.; Oldehinkel, A.J.; Snieder, H.; Biino, G.; Schmidt, R.; Schmidt, H.; Chen, Y.E.; Bandinelli, S.; Dedoussis, G.; Thanaraj, T.A.; Kardia, S.L.R.; Kato, N.; Schulze, M.B.; Girotto, G.; Jung, B.; Böger, C.A.; Joshi, P.K.; Bennett, D.A.; de Jager, P.L.; Lu, X.; Mamakou, V.; Brown, M.; Caulfield, M.J.; Munroe, P.B.; Guo, X.; Ciullo, M.; Jonas, J.B.; Samani, N.J.; Kaprio, J.; Pajukanta, P.; Adair, L.S.; Bechayda, S.A.; de Silva, H.J.; Wickremasinghe, A.R.; Krauss, R.M.; Wu, J.Y.; Zheng, W.; den Hollander, A.I.; Bharadwaj, D.; Correa, A.; Wilson, J.G.; Lind, L.; Heng, C.K.; Nelson, A.E.; Golightly, Y.M.; Wilson, J.F.; Penninx, B.; Kim, H.L.; Attia, J.; Scott, R.J.; Rao, D.C.; Arnett, D.K.; Walker, M.; Koistinen, H.A.; Chandak, G.R.; Yajnik, C.S.; Mercader, J.M.; Tusié-Luna, T.; Aguilar-Salinas, C.A.; Villalpando, C.G.; Orozco, L.; Fornage, M.; Tai, E.S.; van Dam, R.M.; Lehtimäki, T.; Chaturvedi, N.; Yokota, M.; Liu, J.; Reilly, D.F.; McKnight, A.J.; Kee, F.; Jöckel, K.H.; McCarthy, M.I.; Palmer, C.N.A.; Vitart, V.; Hayward, C.; Simonsick, E.; van Duijn, C.M.; Lu, F.; Qu, J.; Hishigaki, H.; Lin, X.; März, W.; Parra, E.J.; Cruz, M.; Gudnason, V.; Tardif, J.C.; Lettre, G.; 't Hart, L.M.; Elders, P.J.M.; Damrauer, S.M.; Kumari, M.; Kivimaki, M.; van der Harst, P.; Spector, T.D.; Loos, R.J.F.; Province, M.A.; Psaty, B.M.; Brandslund, I.; Pramstaller, P.P.; Christensen, K.; Ripatti, S.; Widén, E.; Hakonarson, H.; Grant, S.F.A.; Kiemeney, L.A.L.M.; de Graaf, J.; Loeffler, M.; Kronenberg, F.; Gu, D.; Erdmann, J.; Schunkert, H.; Franks, P.W.; Linneberg, A.; Jukema, J.W.; Khera, A.V.; Männikkö, M.; Jarvelin, M.R.; Kutalik, Z.; Cucca, F.; Mook-Kanamori, D.O.; van Dijk, K.W.; Watkins, H.; Strachan, D.P.; Grarup, N.; Sever, P.; Poulter, N.; Rotter, J.I.; Dantoft, T.M.; Karpe, F.; Neville, M.J.; Timpson, N.J.; Cheng, C.Y.; Wong, T.Y.; Khor, C.C.; Sabanayagam, C.; Peters, A.; Gieger, C.; Hattersley, A.T.; Pedersen, N.L.; Magnusson, P.K.E.; Boomsma, D.I.; de Geus, E.J.C.; Cupples, L.A.; van Meurs, J.BJ.; Ghanbari, M.; Gordon-Larsen, P.; Huang, W.; Kim, Y.T.; Tabara, Y.; Wareham, N.J.; Langenberg, C.; Zeggini, E.; Kuusisto, J.; Laakso, M.; Ingelsson, E.; Abecasis, G.; Chambers, J.C.; Kooner, J.S.; de Vries, P.S.; Morrison, A.C.; North, K.E.; Daviglus, M.; Kraft, P.; Martin, N.G.; Whitfield, J.B.; Abbas, S.; Saleheen, D.; Walters, R.G.; Holmes, M.V.; Black, C.; Smith, B.H.; Justice, A.E.; Baras, A.; Buring, J.E.; Ridker, P.M.; Chasman, D.I.; Kooperberg, C.; Wei, W.Q.; Jarvik, G.P; Namjou, B.; Hayes, M.G.; Ritchie, M.D.; Jousilahti, P.; Salomaa, V.; Hveem, K.; Åsvold, B.O.; Kubo, M.; Kamatani, Y.; Okada, Y.; Murakami, Y.; Thorsteinsdottir, U.; Stefansson, K.; Ho, Y.L.; Lynch, J.A.; Rader, D.J.; Tsao, P.S.; Chang, K.M.; Cho, K.; O'Donnell, C.J.; Gaziano, J.M.; Wilson, P.; Rotimi, C.N.; Hazelhurst, S.; Ramsay, M.; Trembath, R.C.; van Heel, D.A.; Tamiya, G.; Yamamoto, M.; Kim, B.J.; Mohlke, K.L.; Frayling, T.M.; Hirschhorn, J.N.; Kathiresan, S.; Boehnke, M.; Natarajan, P.; Peloso, G.M.; Brown, C.D.; Morris, A.P.; Assimes, T.L.; Deloukas, P.; Sun, Y.V.; Willer, C.J.; VA Million Veteran Program; Global Lipids Genetics ConsortiumIncreased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use1. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels2, heart disease remains the leading cause of death worldwide3. Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS4-23 have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns24. Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately 295,000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine25, we anticipate that increased diversity of participants will lead to more accurate and equitable26 application of polygenic scores in clinical practice.Item Comprehensive evaluation of demographic, socio-economic and other associated risk factors affecting the occurrence of dengue incidence among Colombo and Kandy Districts of Sri Lanka: a cross-sectional study(BioMed Central, 2018) Udayanga, L.; Gunathilaka, N.; Iqbal, M.C.M.; Lakmal, K.; Amarasinghe, U.S.; Abeyewickreme, W.BACKGROUND: Comprehensive understanding of risk factors related to socio-economic and demographic status and knowledge, attitudes and practices (KAP) of local communities play a key role in the design and implementation of community-based vector management programmes, along with the identification of gaps in existing control activities. METHODS: A total of 10 Medical Officers of Health (MOH) areas recording high dengue incidence over the last five years were selected from Colombo (n = 5) and Kandy (n = 5) Districts, Sri Lanka. From each MOH area, 200 houses reporting past dengue incidence were selected randomly as test group (n = 1000 for each district) based on the dengue case records available at relevant MOH offices. Information on socio-economic and demographic status and knowledge, attitudes and practices were gathered using an interviewer administered questionnaire. The control group contained 200 households from each MOH area that had not reported any dengue case and the same questionnaire was used for the assessment (n = 1000 for each district). Statistical comparisons between the test and control groups were carried out using the Chi-square test of independence, cluster analysis, analysis of similarities (ANOSIM) and multi-dimensional scaling (MDS) analysis. RESULTS: Significant differences among the test and control groups in terms of basic demographic and socio-economic factors, living standards, knowledge, attitude and practices, were recognized (P < 0.05 at 95% level of confidence). The test group indicated similar risk factors, while the control group also shared more or less similar characteristics as depicted by the findings of cluster analysis and ANOSIM. Findings of the present study highlight the importance of further improvement in community education, motivation and communication gaps, proper coordination and integration of control programmes with relevant entities. Key infrastructural risk factors such as urbanization and waste collection, should be further improved, while vector controlling entities should focus more on the actual conditions represented by the public on knowledge, attitudes and personal protective practices. CONCLUSIONS: The design of flexible and community friendly intervention programmes to ensure the efficacy and sustainability of controlling dengue vectors through community based integrated vector management strategies, is recommended.