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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item Spatiotemporal distribution of cutaneous leishmaniasis in Sri Lanka and future case burden estimates(Public Library of Science, 2021) Karunaweera, N.D.; Senanayake, S.; Ginige, S.; Silva, H.; Manamperi, N.; Samaranayake, N.; Dewasurendra, R.; Karunanayake, P.; Gamage, D.; de Silva, N.; Senarath, U.; Zhou, G.BACKGROUND: Leishmaniasis is a neglected tropical vector-borne disease, which is on the rise in Sri Lanka. Spatiotemporal and risk factor analyses are useful for understanding transmission dynamics, spatial clustering and predicting future disease distribution and trends to facilitate effective infection control. METHODS: The nationwide clinically confirmed cutaneous leishmaniasis and climatic data were collected from 2001 to 2019. Hierarchical clustering and spatiotemporal cross-correlation analysis were used to measure the region-wide and local (between neighboring districts) synchrony of transmission. A mixed spatiotemporal regression-autoregression model was built to study the effects of climatic, neighboring-district dispersal, and infection carryover variables on leishmaniasis dynamics and spatial distribution. Same model without climatic variables was used to predict the future distribution and trends of leishmaniasis cases in Sri Lanka. RESULTS: A total of 19,361 clinically confirmed leishmaniasis cases have been reported in Sri Lanka from 2001-2019. There were three phases identified: low-transmission phase (2001-2010), parasite population buildup phase (2011-2017), and outbreak phase (2018-2019). Spatially, the districts were divided into three groups based on similarity in temporal dynamics. The global mean correlation among district incidence dynamics was 0.30 (95% CI 0.25-0.35), and the localized mean correlation between neighboring districts was 0.58 (95% CI 0.42-0.73). Risk analysis for the seven districts with the highest incidence rates indicated that precipitation, neighboring-district effect, and infection carryover effect exhibited significant correlation with district-level incidence dynamics. Model-predicted incidence dynamics and case distribution matched well with observed results, except for the outbreak in 2018. The model-predicted 2020 case number is about 5,400 cases, with intensified transmission and expansion of high-transmission area. The predicted case number will be 9115 in 2022 and 19212 in 2025. CONCLUSIONS: The drastic upsurge in leishmaniasis cases in Sri Lanka in the last few year was unprecedented and it was strongly linked to precipitation, high burden of localized infections and inter-district dispersal. Targeted interventions are urgently needed to arrest an uncontrollable disease spread.Item Variants of acan gene associate with severity of lumbar disc degeneration(Sri Lanka Medical Association, 2016) Perera, G.L.R.S.; Wijayaratne, L.S.; Senarath, U.; Dissanayake, P.H.; Karunanayake, A.L.; Dissanayake, V.H.W.INTRODUCTION AND OBJECTIVES: Structural integrity of aggrecan (coded by ACAN gene) plays a major role in lumbar disc degeneration (LDD). Single nucleotide polymorphisms (SNPs) of ACAN gene have been implicated in LDD. The study aimed to determine the associations between SNPs of ACAN gene and the severity of disc space narrowing (DSN) and osteophytes (OS) of lumbar spine in patients with chronic mechanical low back pain (CMLBP). METHOD: A descriptive cross-sectional study was carried out on 120 patients with CMLBP. Lateral lumbar X-rays were assessed for severity of DSN and OS using a semiquantitative scores (grade 0-3). Twenty-seven exonic SNPs of the ACAN gene were genotyped on a Sequenom mass array iPLEX platform. Multiple linear regression analysis was carried out adjusting for age and body mass index. RESULTS: Mean age was 51.46 ± 10.43 years. 82 (68.3%) were females. 30 (25%) were obese. 31 (25.8%) and 47 (39.2%) had grade 1 DSN and AOS respectively, while 42 (35%) and 13 (10.8%) had grade ≥ 2 DSN and AOS, respectively. “A” allele of rs2882676 (regression coefficient (β) = -0.25, p<0.03), “A” allele of rs1042630 (β = -0.28, p<0.01) and “T” allele of rs1042631 (β = -0.28, p<0.02) were negatively associated with the severity of DSN. “T” allele of rs16942341 (β = 0.4, p<0.02) and “G” allele of rs28407189 (β = 0.4, p<0.02) were positively associated with the severity of AOS. CONCLUSION: SNPs of ACAN gene are associated with severity of degenerative changes of the lumbar spine.Item Single nucleotide variants of candidate genes in aggrecan metabolic pathway are associated with lumbar disc degeneration and modic changes(Public Library of Science, 2017) Perera, R.S.; Dissanayake, P.H.; Senarath, U.; Wijayaratne, L.S.; Karunanayake, A.L.; Dissanayake, V.H.W.INTRODUCTION: Lumbar disc degeneration (LDD) is genetically determined and severity of LDD is associated with Modic changes. Aggrecan is a major proteoglycan in the intervertebral disc and end plate. Progressive reduction of aggrecan is a main feature of LDD and Modic changes. OBJECTIVES: The study investigated the associations of single nucleotide variants (SNVs) of candidate genes in the aggrecan metabolic pathway with the severity of LDD and Modic changes. In-silico functional analysis of significant SNVs was also assessed. METHODS: A descriptive cross sectional study was carried out on 106 patients with chronic mechanical low back pain. T1, T2 sagittal lumbar MRI scans were used to assess the severity of LDD and Modic changes. 62 SNVs in ten candidate genes (ACAN, IL1A, IL1B, IL6, MMP3, ADAMTS4, ADAMTS5, TIMP1, TIMP2 and TIMP3) were genotyped on Sequenom MassARRAY iPLEX platform. Multiple linear regression analysis was carried out using PLINK 1.9 in accordance with additive genetic model. In-silico functional analysis was carried out using Provean, SIFT, PolyPhen and Mutation Taster. RESULTS: Mean age was 52.42±9.42 years. 74 (69.8%) were females. The rs2856836, rs1304037, rs17561 and rs1800587 variants of the IL1A gene were associated with the severity of LDD and Modic changes. The rs41270041 variant of the ADAMTS4 gene and the rs226794 variant of the ADAMTS5 gene were associated with severity of LDD while the rs34884997 variant of the ADAMTS4 gene, the rs55933916 variant of the ADAMTS5 gene and the rs9862 variant of the TIMP3 gene were associated with severity of Modic changes. The rs17561 variant of the IL1A gene was predicted as pathogenic by the PolyPhen prediction tool. CONCLUSIONS: SNVs of candidate genes in ACAN metabolic pathway are associated with severity of LDD and Modic changes in patients with chronic mechanical low back pain. Predictions of in-silico functional analysis of significant SNVs are inconsistent.Item Association between pain and disability in patients with chronic mechanical low back pain(Sri Lanka Medical Association, 2015) Perera, G.L.R.S.; Wijayaratne, L.S.; Senarath, U.; Dissanayake, P.H.; Karunanayake, A.L.; Dissanayake, V.H.W.INTRODUCTION AND OBJECTIVES: Low back pain is the leading cause of years lived with disability in developed countries as well as in South Asian countries. The aim of this study is to evaluate the association between the intensity of pain and disability in patients with chronic mechanical low back pain (CMLBP) who attended the rheumatology clinic, National Hospital of Sri Lanka (NHSL). METHOD: This is a descriptive study on 675 patients with CMLBP who attended the rheumatology clinic, NHSL, from May 2012 to May 2014, recruited according to inclusion and exclusion criteria. Intensity of pain was measured using the 101-point numerical pain rating scale (NRS) and the disability was measured using the modified Oswestry Disability Index (MODI). A multiple linear regression model adjusted for age, gender, level of education, duration and frequency of pain and duration of treatment was used to assess the association between the intensity of pain and disability. RESULTS: Majority (482, 71.4%) were females. Mean age was 49.19 ± 11.75 years. Mean score for NRS was 46.79 ± 20.38 and for MODI was 31.77 ± 14.16, while 84.3% had daily pain. Intensity of pain was positively associated with the disability (p<0.01) and the standardized regression coefficient was +0.627 after adjusting for confounders. Frequency of pain, female gender and aging were positively associated with disability (p<0.05) while level of education, and durations of pain and treatment did not reach significant level. Conclusion: Intensity of pain explains 63% of the disability associated with CMLBP. Frequency of pain, female gender and age were also associated with disability.Item Anthropometric patterns among patients with chronic mechanical low back pain(Sri Lanka Medical Association, 2014) Perera, G.L.R.S.; Wijayaratne, L.S.; Senarath, U.; Dissanayake, P.H.; Karunonayake, A.L.; Dissanayake, V.H.W.INTRODUCTION AND OBJECTIVES: Anthropometric parameters may have an association with chronic mechanical low back pain (CMLBP). Our aim was to evaluate the anthropometric patterns; body mass index (BMI), waist circumference (WCJ and waist to height ratio (WHtR) among patients with CMLBP. METHODS: A total of 519 patients with CMLBP were recruited from a cohort of patients attending the rheumatology clinic at the National Hospital of Sri Lanka. Anthropometric parameters were measured using recommended techniques. Independent samples t test and one way ANOVA were used to compare the means of anthropometric parameters. The means of BM1, WC of the patients were compared with means of a national representative sample of Sri Lankan adults. Asian anthropometric cut offs were used to define obesity and abdominal obesity. RESULTS: 372 (71.7%) were females and mean age was 49.64 years (50=1.81). The mean BMI was 26.31 kg/m2 ($0=4.77), WC 85.98cm (50=10.65) and WHtR 0.56 (SD=0.08). Females had significantly higher BMI 27.24 kg/m2 ($0=4.68), WC 86.84cm (SD=10.59) and WHtR 0.577 (50=0.072) compared to males' BMI 23.95 kg/m2, SD=4.14), WC 83.79cm, (50=10.51) and WHtR 0.512 ($0=0.661) (p<0.05). Mean BMI, WC and WHtR increased with age (/xQ.OOl). CMLBP patients had high BMI and WC compared to the national representative sample of Sri Lankan adults (p<0.001). Females had more obesity and abdominal obesity compared to males (p<0.001). CONCLUSIONS: High BMI and WC were seen in patients with CMLBP and the values increased with age. Females were obese and had high abdominal obesity, which may have contributed to CMLBP.