Medicine
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Item Patterns of alcohol use and occurrence of alcoholic fatty liver disease: a prospective, community cohort, 7-year follow-up study(Sri Lanka Medical Association, 2017) Niriella, M.A.; de Silva, S.T.; Kasturiratne, A.; Perera, K.R.; Subasinghe, S.K.C.E.; Kodisinghe, S.K.; Piyaratna, T.A.C.L.; Vithiya, K.; Dassanayake, A.S.; de Silva, A.P.; Pathmeswaran, A.; Wickremasinghe, A.R.; Kato, N.; de Silva, H.J.INTRODUCTION & OBJECTIVES: Data is limited on alcoholic fatty liver disease (AFLD). We investigated patterns of alcohol use and AFLD, among urban, adult, Sri Lankans. METHODS: Study population (selected by age-stratified random sampling from Ragama MOH-area) was screened initially in 2007 (35-64 years) and re-evaluated in 2014. On both occasions they were assessed by structured-interview, anthropometric measurements, liver ultrasound, biochemical and serological tests. AFLD was diagnosed on ultrasound criteria, unsafe alcohol consumption (Asian standards: males>14units, females>7units per week) and absence of hepatitis B/C markers. Controls were individuals with unsafe alcohol consumption, but had no ultrasound criteria of AFLD. Case-control genetic-association for PNPLA3 (rs738409) polymorphism for AFLD was performed. RESULTS: A total of 2983/3012 (99%) had complete data. 272/2983(9.1%) were unsafe-drinkers [males- 70; mean-age 51.9 (SD-8.0) years]. 86/2983 (2.9%) of the cohort and 86/272 (31.6%) of unsafe-drinkers had AFLD [males-85; mean-age 50.2 (SD-8.6) years]. Males [p<0.001], increased waist circumference (WC) [p=0.001], BMI>23kg/m2 [p<0.001], raised triglycerides (TG) [p<0.001], low education level (LEL-not completed secondary-education) [p<0.01] and low monthly household-income (23kg/m2 [p<0.001], raised TG [p<0.001] and LEL [p<0.05] independently predicted incident-AFLD. The genetic association study [133-cases (combined 2007-2014), 97-controls] showed no association with AFLD at PNPLA3 (rs738409). CONCLUSION: The prevalence of AFLD was 2.9% in 2007 and annual incidence among heavy drinkers, after 7-year follow-up was 5.7%. Incident-AFLD was associated with males, obesity, raised TG and LEL.Item Incidence, prevalence and demographic and life style risk factors for obesity among urban, adult Sri Lankans: a community cohort follow-up study(Sri Lanka Medical Association, 2017) Niriella, M.A.; de Silva, S.T.; Kasturiratne, A.; Kottachchi, D.; Ranasinghe, R.M.A.G.; Dassanayake, A.S.; de Silva, A.P.; Pathmeswaran, A.; Wickremasinghe, A.R.; Kato, N.; de Silva, H.J.INTRODUCTION & OBJECTIVES: Obesity is a global problem. Data from the South Asian region is limited. METHODS: In a cohort follow-up study we investigated obesity among urban, adult, Sri Lankans (35-64y; selected by age-stratified random sampling from Ragama-MOH area; initial screening 2007; re-evaluation 2014). On both occasions structured interview, anthropometry, liver ultrasound, biochemical and serological tests were performed. Total body fat (TBF) and visceral fat percentage (VFP) were assessed by impedance in 2014. General-obesity (GO) was BMI>25kg/m2. Central-obesity (CO) was waist circumference (WC)>90cm males and WC>80cm females. Multinomial logistic regression was fitted to assess associations. RESULTS: In 2007 (n=2967), 614 (20.7%) were overweight [51.9%-women], 1161(39.1%) had GO [65.9%-women] and 1584(53.4%) had CO [71%-women]. Females (p<0.001), raised-TG (p<0.001), low-HDL (p<0.001), diabetes (p<0.001), hypertension (p<0.001), NAFLD (p<0.001), and low household income (p<0.001) were significantly associated with prevalent GO and CO respectively. Additionally, increased-age (p=0.05), low-educational level (p<0.001) and unhealthy eating (p<0.001) were associated with prevalent CO. Inadequate physical activity was not associated with either. 2137 (72%) attended follow-up in 2014. Of those who were initially non-obese who attended follow-up, 189/1270 (14.9%) [64% women] had developed GO (annual-incidence 2.13%) and 206/947 (21.9%) [56.3% women] had developed CO (annual incidence 3.12%) after 7 years. TBF and VFP significantly correlated with incident GO and CO (p<0.001). Female gender (OR-1.78, p<0.001; 2.81, p<0.001) and NAFLD (OR-2.93, p<0.001; OR-2.27, p<0.001) independently predicted incident GO and CO respectively. CONCLUSION: The prevalence and incidence of GO and CO were high in this cohort. Both incident GO and CO were strongly associated with female gender and NAFLD.Item Lean non-alcoholic fatty liver disease (Lean-NAFLD): characteristics and risk factors from a community cohort follow up study(Sri Lanka Medical Association, 2016) Niriella, M.A.; de Silva, S.T.; Kasturiratne, A.; Perera, K.R.; Subasinghe, S.K.C.E.; Kodisinghe, S.K.; Piyaratna, T.A.C.L.; Vithiya, K.; Dassanayake, A.S.; de Silva, A.P.; Pathmeswaran, A.; Wickremasinghe, A.R.; Kato, N.; de Silva, H.J.INTRODUCTION AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is usually associated with obesity. However, some NAFLD patients are lean. We assessed the characteristics and risk factors for lean-NAFLD. METHOD: In a community cohort follow up study (initial screening-2007, re-evaluation-2014), NAFLD was established on USS criteria and exclusion of alcohol overuse and secondary causes. Lean (BMI <23 kg/m2) and non-lean (BMI ≥23 kg/m2) NAFLD were compared. The two groups were compared for differences in gender, diabetes, hypertension, hypertriglyceridemia, low-HDL, weight and waist circumference (WC) at baseline. They were also compared for differences in development of incident diabetes, hypertension, hypertriglyceridemia, low-HDL, and change in weight and WC. RESULTS: 678 (69.6%) individuals with NAFLD detected in 2007 presented for follow up in 2014. 78(11.5%) [males-32(41%); mean-age 53.7(SD-7.1) years] were lean and 600(88.5%) [males-191(31.8%); mean-age 52.3(SD-7.5) years] were non-lean. Hypertension (p=0.007) and a smaller WC (<90cm for males, <80cm for females) (p<0.001) were associated with lean-NAFLD. After 7 years, change in BMI was less (p=0.022) among lean-NAFLD. There were no differences in change in WC or incident metabolic co-morbidities. Of those who did not have NAFLD in 2007, 746 developed incident NAFLD in 2014; lean-NAFLD 193/746 (25.9%) [males-100(51.8%); mean age 59.6(SD-7.5)], non-lean-NAFLD 553/746 (74.1%) [males-201(36.3%); mean age 58.2(SD-7.7)]. On logistic regression analysis, presence of diabetes (p=0.002, OR 2.1) and raised WC (p=0.003, OR 1.7) were associated with incident lean-NAFLD. CONCLUSIONS: Among individuals with NAFLD, lean-NAFLD is associated with hypertension and smaller WC. In the community, diabetes and bigger WC predict incident lean-NAFLD.Item Incidence and risk factors for non-alcoholic fatty liver disease in an urban, adult Sri Lankan population – a community cohort follow-up study(Sri Lanka Medical Association, 2016) Niriella, M.A.; Kasturiratne, A.; de Silva, S.T.; Perera, K.R.; Subasinghe, S.K.C.E.; Kodisinghe, S.K.; Piyarathna, T.A.C.L.; Vithiya, K.; Dassanayake, A.S.; de Silva, A.P.INTRODUCTION: In 2007, we reported a 33% prevalence of non-alcoholic fatty liver disease (NAFLD) and its association with PNPLA3(rs738409) gene polymorphism in an urban, adult Sri Lankan population. OBJECTIVES: This study investigated incidence and risk factors for NAFLD after seven years follow-up. METHOD: The study population (42-71-year-olds, selected by age-stratified random sampling from the Ragama MOH area) was screened initially in 2007 and re-evaluated in 2014. On both occasions they were assessed by structured interview, anthropometric measurements, liver ultrasound, biochemical and serological tests. NAFLD was diagnosed on established ultrasound criteria, safe alcohol consumption and absence of hepatitis B/C markers. Non-NAFLD controls did not have any ultrasound criteria for NAFLD. An updated case-control genetic association study for 10 selected genetic variants and incident NAFLD was also performed. RESULTS: 2155/2985 (72.2%) of the original cohort attended follow-up [1244-women, 911-men; mean-age 59.2(SD, 7.7) years]. 1322 [839 women; mean-age 58.9 (SD, 7.6) years] had NAFLD. Out of 795 [466 women] who initially did not have NAFLD, 365 [226 women, mean-age 58.6(SD,7.9) years] had developed NAFLD after 7 years (annual incidence-6.6%). Increased waist circumference [p=0.001], BMI>23kg/m2 [p<0.001] and raised plasma triglycerides [p<0.05] independently predicted incident NAFLD. The updated genetic association study (1310 cases, 427 controls) showed borderline association with NAFLD at 2/10 candidate loci: PPP1R3B(rs4240624), PNPLA3(rs738409) (one-tailed p=0.044 and 0.033, respectively). CONCLUSIONS: In this community cohort follow-up study, the annual incidence of NAFLD was 6.6%. Incident NAFLD was associated with features of metabolic syndrome, and showed tendency of association with PNPLA3 and PPP1R3B gene polymorphisms.Item Modified mismatch polymerase chain reaction-restriction fragment length polymorphism detected mutations in codon 12 and 13 of exon 2 of K-ras gene in colorectal cancer patients and its association with liver metastases: Data from a South Asian country(Medknow Publications, 2016) Faleel, F.D.; Zoysa, M.I.; Lokuhetti, M.D.; Gunawardene, Y.I.N.S.; Chandrasekharan, N.V.; Dassanayake, R.S.AIM: Mutations in K-ras codon 12 and 13 of exon 2 are known to affect prognosis and impart resistance to anti-epidermal growth factor monoclonal antibody therapy in colorectal carcinoma (CRC). Our aim was to investigate the utility value of modified mismatch polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay to detect mutation in K-ras codons of CRC patients and to relate the mutational status to liver metastasis. METHODOLOGY: Mismatch PCR-RFLP was developed to detect K-ras mutations in DNA isolated from paraffinized tumor tissue of thirty CRC patients. All patients had 5 year follow-up data to detect liver metastasis. Cross-tabulations were generated between K-ras mutations and the metastatic status. The Chi-square test was used to indicate statistical significance of the association. RESULTS: Of the 30 CRC patients investigated, K-ras mutations of codons 12 and/or 13 of exon 2 were detected in 14 (46.6%). Meanwhile, 13 patients (43.3%) were observed to have developed liver metastases. There was a significant association between the presence of the K-ras mutation in codon 12 and the occurrence of liver metastasis (χ2 = 4.693, P = 0.030) on the contrary to the mutation in codon 13 to which such occurrence of liver metastases was not seen (χ2 = 1.884, P = 0.169). CONCLUSION: Codon 12 of exon 2 of K--ras gene detected by modified mismatch PCR-RFLP assay is significantly associated with liver metastasis in CRC patients during the first 5 years after surgery. Thus, modified mismatch PCR-RFLP protocol is a suitable method in this setting to detect K-ras gene mutations predicting liver metastasis in CRC patients.Item Recurrence of graft steatosis after liver transplantation for cryptogenic cirrhosis in recently commenced liver transplant program(Springer India, 2016) Siriwardana, R.C.; Niriella, M.A.; Dassanayake, A.S.; Liyanage, C.A.H.; Gunetilleke, B.; de Silva, H.J.Non-alcoholic fatty liver disease (NAFLD) seems to recur in at least one third of patients transplanted for non-alcoholic steatohepatitis (NASH)-related cirrhosis. While, NASH recurrence does not seem to affect overall graft and patient survival up to 10 years, cardiovascular and infection-related morbidity and mortality seem to be increased in these patients. This report looks at the graft histology in patients who were transplanted for NASH-related cirrhosis after short-term follow up. We report a high prevalence of recurrent NAFLD in liver grafts post-transplant among five patients. The degree of steatosis noted among the recipients is alarming.Item Classification of neck/shoulder pain in epidemiological research: a comparison of personal and occupational characteristics, disability and prognosis among 12,195 workers from 18 countries(Elsevier-North-Holland, 2016) Sarquis, L.M.; Coggon, D.; Ntani, G.; Walker-Bone, K.; Palmer, K.T.; Felli, V.E.; Harari, R.; Barrero, L.H.; Felknor, S.A.; Gimeno, D.; Cattrell, A.; Vargas-Prada, S.; Bonzini, M,; Solidaki, E.; Merisalu, E.; Habib, R.R.; Sadeghian, F.; Kadir, M.M.; Warnakulasuriya, S.S.; Matsudaira, K.; Nyantumbu, B.; Sim, M.R.; Harcombe, H.; Cox, K.; Marziale, M.H.; Harari, F.; Freire, R.; Harari, N.; Monroy, M.V.; Quintana, L.A.; Rojas, M.; Harris, E.C.; Serra, C.; Martinez, J.M.; Delclos, G.; Benavides, F.G.; Carugno, M.; Ferrario, M.M.; Pesatori, A.C.; Chatzi, L.; Bitsios, P.; Kogevinas, M.; Oha, K.; Tiina; Freimann; Sadeghian, A.; Peiris-John, R.J.; Sathiakumar, N.; Wickremasinghe, A.R.; Yoshimura, N.; Kelsall, H.L.; Hoe, V.C.; Urquhart, D.M.; Derrett, S.; McBride, D.; Herbison, P.; Gray, A.; Salazar Vega, E.J.To inform case-definition for neck/shoulder pain in epidemiological research, we compared levels of disability, patterns of association and prognosis for pain that was limited to the neck or shoulders (LNSP) and more generalised musculoskeletal pain that involved the neck or shoulder(s) (GPNS). Baseline data on musculoskeletal pain, disability and potential correlates were collected by questionnaire from 12,195 workers in 47 occupational groups (mostly office workers, nurses, and manual workers) in 18 countries (response rate = 70%). Continuing pain after a mean interval of 14 months was ascertained through a follow-up questionnaire in 9,150 workers from 45 occupational groups. Associations with personal and occupational factors were assessed by Poisson regression and summarised by prevalence rate ratios (PRRs). The one-month prevalence of GPNS at baseline was much greater than that of LNSP (35.1% vs. 5.6%), and it tended to be more troublesome and disabling. Unlike LNSP, the prevalence of GPNS increased with age. Moreover, it showed significantly stronger associations with somatising tendency (PRR 1.6 vs. 1.3) and poor mental health (PRR 1.3 vs. 1.1); greater variation between the occupational groups studied (prevalence ranging from 0% to 67.6%) that correlated poorly with the variation in LNSP; and was more persistent at follow-up (72.1% vs. 61.7%). Our findings highlight important epidemiological distinctions between sub-categories of neck/shoulder pain. In future epidemiological research that bases case definitions on symptoms, it would be useful to distinguish pain which is localised to the neck or shoulder from more generalised pain that happens to involve the neck/shoulder region.Item Incidence and risk factors for Non-Alcoholic Fatty Liver Disease in an urban, adult Sri Lankan population – a community cohort follow-up study(Sage Publishing, 2015) Niriella, M.; Kasturiratne, A.; de Silva, S.; Perera, R.; Subasinghe, C.; Kodisinghe, K.; Priyantha, C.; Rishikeshavan, V.; Dassanayake, A.; de Silva, A.; Pathmeswaran, A.; Kato, N.; de Silva, H.J.INTRODUCTION: We previously reported a community prevalence of 33% for NAFLD in an urban, adult Sri Lankan population. We also found a significant association between patatin-like phospholipase domain containing 3 (PNPLA3) gene rs738409 polymorphism, and susceptibility to NAFLD in the same population, after testing 10 selected single nucleotide polymorphisms (SNPs) in a case control study. AIMS & METHODS: The aim of this study was to assess the incidence and risk factors for NAFLD in this population after seven years of follow-up. The study population consisted of 42-71-year-old adults, originally selected by age stratified random sampling from electoral lists from Ragama, Sri Lanka. The target population was screened initially in 2007 and subsequently invited back for re-evaluation in 2014. On both occasions they were assessed using a structured interview, clinical and anthropometric measurements, liver ultrasound, and biochemical and serological tests. NAFLD was diagnosed on established ultrasound criteria for fatty liver (two out of three criteria: increased echogenecity of the liver compared to kidney and spleen, obliteration of the vascular architecture of the liver and deep attenuation of the ultrasonic signal), safe alcohol consumption (Asian standards: 514 units/week for men, 57 units/week for females) and absence of hepatitis B and C markers. Non-NAFLD controls were defined as subjects who did not have any of the ultrasound criteria for NAFLD. We also performed an updated case-control study to investigate associations of selected genetic variants with incident NAFLD [SNPs: PNPLA3 (rs738409), LYPLAL1 (rs12137855), GCKR (rs780094), PPP1R3B (rs4240624) and NCAN (rs2228603), APOC3 (rs2854117 and rs2854116), ADIPOR2 (rs767870) and STAT3 (rs6503695 and rs9891119)]. RESULTS: Of the 2985 original study participants, 2155 (72.2%) (1244 women and 911 men; mean age 59.2 years [SD, 7.7]) participated in the follow-up assessment. 1322 [mean age 58.9 years (SD, 7.6), 483 (53.0%) men and 839 (67.4%) women] had NAFLD. Out of 795 [466 (58.6%) women] participants who did not have NAFLD in the original study, 365 [226 (61.9%) women, mean age 58.6 years (SD, 7.9)] had developed NAFLD after 7 years, giving an annual incidence rate 6.6%. On multivariate analysis, increased waist circumference [OR 1.96(1.30 – 2.97), p=0.001], BMI4 23 kg/m2 [OR 2.93(1.99 – 4.30), p50.001] and raised plasma triglycerides (TG) [OR 1.49(1.03 – 2.13), p=0.03] were independently predictive of incident NAFLD in this cohort, while raised BP and reduced HDL, were not. In the updated association study involving 1310 cases and 427 controls, we found borderline association with NAFLD at two of the 10 candidate loci: rs4240624 at PPP1R3B and rs738409 at PNPLA3 (one-tailed P=0.044 and 0.033, respectively). CONCLUSION: In this community cohort follow-up study in an urban, adult population in Sri Lanka, the annual incidence of NAFLD was 6.6%. Incident NAFLD was associated with features of the metabolic syndrome, and showed tendency of association at PNPLA3 and PPP1R3B gene polymorphisms. Disclosure of Interest: None declaredItem Evaluation of the effectiveness of the national vitamin A supplementation programme among school children in Sri Lanka(Cambridge University Press, 2007) Madatuwa, T.M.; Mahawithanage, S.T.C.; Chandrika, U.G.; Jansz, E.R.; Wickremasinghe, A.R.The Ministry of Health in Sri Lanka commenced a vitamin A supplementation programme of school children with a megadose of 105 micromol (100,000 IU) vitamin A in school years 1, 4 and 7 (approximately 5-, 9- and 12-year-olds, respectively) in 2001. We evaluated the vitamin A supplementation programme of school children in a rural area of Sri Lanka. A cross-sectional study was conducted among children supplemented with an oral megadose of vitamin A (105 micromol; n 452) and children not supplemented (controls; n 294) in Grades 1-5. Children were clinically examined and a sample of blood was taken for serum vitamin A concentration estimation by HPLC. Socio-demographic information was obtained from children or mothers. Supplemented children had a higher proportion of males and stunted children, were younger and lived under poorer conditions as compared to controls. There was no difference in the prevalences of eye signs and symptoms of vitamin A deficiency in the two groups. Supplemented children had higher serum vitamin A concentrations than controls (1.4 (SD 0.49) micromol/l v. 1.2 (SD 0.52) micromol/l). The serum vitamin A concentrations were 1.6 (SD 0.45), 1.4 (SD 0.50), 1.3 (SD 0.44) and 1.1 (SD 0.43) micromol/l in children supplemented within 1, 1-6, 7-12 and 13-18 months of supplementation, respectively. Vitamin A concentrations were significantly greater than controls if supplementation was carried out within 6 months after adjustment. The oral megadose of 105 micromol vitamin A maintained serum vitamin A concentrations for 6 months in school children.Item Prospective evaluation of sutured, continuous, and interrupted single layer colonic anastomoses(Taylor and Francis, 1995) Deen, K.I.; Smart, P.J.OBJECTIVE: To evaluate the merits of continuous and interrupted colonic anastomoses. DESIGN: Prospective non-randomised study. SETTING: District hospital, UK. SUBJECTS: 53 Patients (24 male and 29 female) of whom 26 underwent continuous and 27 interrupted sutured colonic anastomoses. MAIN OUTCOME MEASURES: Mortality at 30 days, time taken to complete anastomosis, anastomotic dehiscence and anastomotic stricture. RESULTS: No patient died within 30 days. There were no significant differences in (median, range) time taken to complete the anastomosis (continuous: 15 (7-23) minutes; interrupted: 26 (10-34) minutes, p = 0.27); anastomotic leak rate (continuous 1; interrupted 1) and anastomotic stricture (continuous 1 and interrupted 1). Patients were followed up for a mean of 15 months after continuous and 18 months after interrupted colonicanastomoses. CONCLUSION: As both techniques were equally safe, it is probable that the type of colonic anastomosis done will remain a matter of individual preference.