Browsing by Author "Dissanayake, V.H.W."

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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.
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.
Associations between disc space narrowing, anterior osteophytes and disability in chronic mechanical low back pain: a cross sectional study
(BioMed Central, 2017) Perera, R.S.; Dissanayake, P.H.; Senarath, U.; Wijayaratne, L.S.; Karunanayake, A.L.; Dissanayake, V.H.W.
BACKGROUND: Radiographic features of lumbar disc degeneration (LDD) are common findings in patients with chronic mechanical low back pain; however, its role in disability and intensity of pain is debatable. This study aims to investigate the associations of the x-ray features of LDD and lumbar spondylolisthesis with severity of disability and intensity of pain. METHODS: A cross-sectional study was conducted on 439 patients with chronic mechanical low back pain who attended the rheumatology clinic, National Hospital of Sri Lanka, Colombo, from May 2012 to May 2014. Severity of disability was measured using Modified Oswestry Disability Index and intensity of pain was assessed using numeric rating scale (0-100). X-ray features of LDD (disc space narrowing, anterior osteophytes and overall LDD) and spondylolisthesis were assessed in lateral recumbent lumbar x-rays (L1/L2 to L5/S1) and graded by a consultant radiologist blinded to clinical data. Generalised linear model with linear response was used to assess the associations of x-ray features of LDD with severity of disability and intensity of pain adjusting for age, gender, body mass index and pain radiating into legs. RESULTS: Mean age was 48.99 ± 11.21 and 323 (73.58%) were females. 87 (19.82%) were obese. Mean severity of disability was 30.95 ± 13.67 and mean intensity of pain was 45.50 ± 20.37. 69 (15.72%), 26 (5.92%) and 85 (19.36%) patients had grade 2 disc space narrowing, anterior osteophytes and overall LDD, respectively. 51 (11.62%) patients had lumbar spondylolisthesis. Grade of disc space narrowing and overall LDD were not associated with severity of disability or intensity of pain. The presence of lumbar spondylolisthesis was associated with severity of disability. Female gender and pain radiating into legs were associated with severity of disability and intensity of pain. Advancing age was associated with x-ray features of LDD and lumbar spondylolisthesis. CONCLUSIONS: Lumbar spondylolisthesis is associated with severity of disability in patients with chronic mechanical low back pain. Associations of x-ray features of LDD with severity of disability and intensity of pain are inconclusive. Female gender and pain radiating into legs are significant confounders.
Changing phenotype, early clinical course and clinical predictors of irritable bowel syndrome in Sri Lanka: a prospective, multi-centre descriptive study
(Sri Lanka Medical Association, 2017) Niriella, M.A.; Kodisinghe, S.K.; Nanayakkara, S.D.; Silva, K.T.M.; Rajapakshe, N.; Luke, D.; de Silva, A.P.; Navarathne, N.M.M.; Dissanayake, V.H.W.; Jayasekara, R.W.; de Silva, H.J.
INTRODUCTION & OBJECTIVES: Incidence of inflammatory bowel disease (IBD) is increasing in the Asia Pacific, with changes in phenotype and disease course been reported. METHODS: Ulcerative colitis (UC) and Crohn disease (CD) cases from four national referral centres were included. Phenotype was compared for cases [Group-1/G1-diagnosed between June/2003-December/2009, Group-2/G2-January/2010-June/2016]. Early clinical course (ECC) [complicated disease (Comp D-stricturing/penetrating CD, extensive-UC/pancolitis), treatment refractory disease (TRD-frequently-relapsing, steroid-dependent/refractory, biologics), disease complications (DC-perforation/bleeding/colectomy/malignancy)] among disease duration <3 years, and clinical predictors (CP) of CompD/TRD/DC among disease duration >1 year were also assessed. RESULTS: A total of 452-cases [G1: UC-89 (78.8%), CD-24 (21.2%); G2: UC-197 (58.1%), CD-142 (41.9%)] were included. G2 had a higher proportion of CD (p<0.001). In both groups, leftsided colitis (E2) for UC, ileo-colonic (L3)/non-stricturing, non-penetrating (B1) for CD predominated. More penetrating-CD (B3) in G2 (p<0.01) and more stricturing-CD (B2) in G1 (p<0.05) were noted. ECC was assessed in 293 patients [UC-168 (57.3%), CD-125 (42.7%)]. Among UC: extensive/pan-colitis (E3)-40 (24.5%), severe (S3)-38 (42.2%); among CD:severe episodes-15 (25.9%), stricturing (B2)/penetrating(B3)-18 (14.7%), perianal-disease (P)-29 (23.4%). TRD was seen in 19 (11.3%)-UC and 17 (10.1%)-CD. Immunomodulator use was-70 (41.7%)/93 (74.4%), and anti-TNF use was 3 (1.8%)/12 (9.6%) respectively for UC and CD. Complications for UC: bleeding-6 (3.6%), malignancy-1 (0.6%), surgery-3 (1.8%); for CD: stricture-6 (4.9%), perforation-3 (2.4%), malignancy-1 (0.8%), surgery-2 (1.6%). CP were assessed in 373 [UC-266 (71.3%), CD 107 (28.7%)]. EIM of joints predicted CompD in UC/CD (OR-1.94/OR-2.28). Family history (OR=8.64) and EIM of joints (OR=10.07) predicted DC in UC. CONCLUSION: There was an increase in CD during the study period, but no changes in disease phenotype for UC or CD. Although admissions with CompD were common for UC (but not CD), few patients had TRD or DCs indicating a relatively benign early disease course. Family history, EIM of joints predicted poor outcomes in UC, EIM of joints predicted a poor outcome in CD.
Demographics, pathological characteristics and survival in urothelial bladder cancer in a cohort of Sri Lankan patients.
(The Sri Lanka Medical Association, 2022) Malalasekera, A.P.; Ediriweera, D.; Goonewardena, S.A.S.; Perera, N.D.; Abeygunasekara, A.; Jayasekara, R.W.; Wettasinghe, K.; Dissanayake, V.H.W.; Lokuhetty, M.D.S.
INTRODUCTION: Bladder cancer has the 9th highest incidence among Sri Lankan males. This study describes the demographic profiles and survival in bladder cancer patients at two tertiary care centres in Sri Lanka. METHODS: A group of patients with urothelial bladder cancer, presenting for the first time for definitive treatment, were prospectively enrolled from 2013 to 2017. RESULTS: There were sixty-six patients, with median age of 65 years and male to female ratio of 7:1. Histopathologically pTa 24%, pT1 47% and pT2 29%. Of the pT1 tumours 61% were low grade (LG). The majority (71%) of non-muscle invasive bladder cancer (NMIBC) patients underwent transurethral resection of bladder tumour only. For the entire cohort the 5-year overall survival was 59% and cancer specific survival (CSS) was 65%. CSS in NMIBC was 75% and 30% in muscle invasive bladder cancer (MIBC). The 5-year female CSS (22%) was significantly lower than in males (71%). CONCLUSION: Our cohort has a high male to female ratio. The percentage of MIBC was lower than reported in previous Sri Lankan studies. Of the pT1 tumours there is a higher percentage of pT1 LG patients in comparison to Western reports. There is low utilisation of intravesical mitomycin / bacillus Calmette–Guérin (BCG) in the treatment of NMIBC. The 5-year CSS in the Sri Lankan (lower middle-income economy) cohort lies between the values of high-income economies and upper middle-income economies in Asia. The reasons for poor CSS among Sri Lankan women with bladder cancer needs to be further investigated.
Genetic associations of inflammatory bowel disease in a South Asian population
(Baishideng Publishing Group, 2018) Niriella, M.A.; Liyanage, I.K.; Kodisinghe, S.K.; Silva, A.P.; Rajapakshe, N.; Nanayakkara, S.D.; Luke, D.; Silva, T.; Nawarathne, M.; Peiris, R.K.; Kalubovila, U.P.; Kumarasena, S.R.; Dissanayake, V.H.W.; Jayasekara, R.W.; de Silva, H.J.
AIM: To estimate prevalence and phenotypic associations of selected inflammatory bowel disease (IBD)-associated genetic variants among Sri Lankan patients. METHODS: A case study of histologically confirmed ulcerative colitis (UC) or Crohn's disease (CD) patients with ≥ 1 year disease duration, who were compared to unrelated, gender-matched, healthy individuals as controls, was conducted at four major centers in Sri Lanka. Phenotypic data of the cases were obtained and all participants were genotyped for 16 selected genetic variants: IL12B:rs1045431, IL23R:rs11805303, ARPC2:rs12612347, IRGM:rs13361189, IL26/IL22:rs1558744, CDH1:rs1728785, IL10:rs3024505, FCGR2A:rs3737240, PTGER4:rs4613763, IL17REL/PIM3:rs5771069, HNF4a:rs6017342, STAT3:rs744166, SMURF1:rs7809799, LAMB1:rs886774, HLA-DRB5, DQA1, DRB1, DRA:rs9268853, MST1, UBA7, and APEH:rs9822268. The genotypes of all variants were in Hardy-Weinberg Equilibrium (P > 10-3). To account for multiple hypothesis testing, P-values < 0.003 were considered significant. RESULTS: A total of 415 patients and 465 controls were recruited. Out of the single nucleotide polymorphisms (SNPs) tested, the majority were not associated with IBD in Sri Lankans. Significant positive associations were noted between rs886774 (LAMB1-gene) and UC (odds ratio (OR) = 1.42, P = 0.001). UC patients with rs886774 had mild disease (OR = 1.66, P < 0.001) and remained in remission (OR = 1.48, P < 0.001). A positive association was noted between rs10045431 (IL 12B gene) and upper gastrointestinal involvement in CD (OR = 4.76, P = 0.002). CONCLUSION: This confirms the heterogeneity of allelic mutations in South Asians compared to Caucasians. Most SNPs and disease associations reported here have not been described in South Asians.
The new normal of medical education - challenges and opportunities
(South East Asia Regional Association for Medical Education (SEARAME), 2020) Karunathilake, I.M.; Dissanayake, V.H.W.; Yasawardena, S.; Abegunawardena, A.; Raviraj, S.; Wijesinghe, P.S.; Anthony, A.A.; Wijesinghe, R.A.N.K.; Bowatte, S.; Wickramaratne, N.; Pathirana, K.D.; Pilapitiya, S.; Edirisinghe, S.; Hettiarachchi, D.; Kohombange, C.; Olipeliyawa, A.
No abstract available
The Pattern of KRAS mutations in metastatic colorectal cancer: a retrospective audit from Sri Lanka
(Biomed Central, 2017) Sirisena, N.D.; Deen, K.I.; Mandawala, D.E.N.; Herath, P.; Dissanayake, V.H.W.
Activating mutations in the KRAS gene, found in approximately 53% of metastatic colorectal cancer (mCRC) cases, can render epidermal growth factor receptor (EGFR) inhibitors ineffective. Regional differences in these mutations have been reported. This is the first study which aims to describe the pattern of KRAS mutations in a Sri Lankan cohort of mCRC patients. RESULTS: The KRAS genotypes detected in mCRC patients which have been maintained in an anonymized database were retrospectively analyzed. Of the 108 colorectal tissue samples tested, 25 (23.0%) had KRAS mutations. Overall, there were 68 (63.0%) males and 40 (37.0%) females. Among the KRAS positive cases, there were 14 (56.0%) males and 11 (44.0%) females. Their age distribution ranged from 29 to 85 years with a median age of 61 years. There were 15 patients (60.0%) with point mutations in codon 12 while 10 (40.0%) had a single mutation in codon 13. The most common KRAS mutation identified was p.Gly13Asp (40.0%), followed by p.Gly12Val (24.0%). Other mutations included p.Gly12Cys (12.0%), p.Gly12Ser (12.0%), p.Gly12Asp (8.0%), and p.Gly12Arg (4.0%). The codon 13 mutation was a G>A transition (40.0%), while G>T transversions (32.0%), G>A transitions (24.0%), and G>C transversions (4.0%) were found in the codon 12 mutations. The frequency of KRAS mutations was similar to that reported for Asian patients. However, in contrast to several published studies, the G>A transition in codon 12 (c.35G>A; p.Gly12Asp), was not the most common mutation within codon 12 in our cohort. This may be a reflection of the genetic heterogeneity in the pattern of KRAS mutations in mCRC patients but valid conclusions cannot be drawn from these preliminary findings due to the small size of the study sample.
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.
Variants of ACAN are associated with severity of lumbar disc herniation in patients with chronic low back pain
(Public Library of Science, 2017) Perera, R.S.; Dissanayake, P.H.; Senarath, U.; Wijayaratne, L.S.; Karunanayake, A.L.; Dissanayake, V.H.W.
INTRODUCTION: Disc herniation is a complex spinal disorder associated with disability and high healthcare cost. Lumbar disc herniation is strongly associated with disc degeneration. Candidate genes of the aggrecan metabolic pathway may associate with the severity of lumbar disc herniation. OBJECTIVES: This study evaluated the association of single nucleotide variants (SNVs) of the candidate genes of the aggrecan metabolic pathway with the severity of lumbar disc herniation in patients with chronic mechanical low back pain. In addition, we assessed the in-silico functional analysis of the significant SNVs and association of their haplotypes with the severity of lumbar disc herniation. METHODS: A descriptive cross sectional study was carried out on 106 patients. Severity of disc herniation and disc degeneration were assessed on T2-weighted mid sagittal lumbar MRI scan. Sixty two exonic SNVs of ten candidate genes of aggrecan metabolic pathway (ACAN, IL1A, IL1B, IL6, MMP3, ADAMTS4, ADAMTS5, TIMP1, TIMP2 and TIMP3) were genotyped on a Sequenom MassARRAY iPLEX platform. Multivariable linear regression analysis was carried out using PLINK 1.9 software adjusting for age, gender, body mass index and severity of disc degeneration. Four online bioinformatics tools (Provean, SIFT, PolyPhen and Mutation Taster) were used for in-silico functional analysis. RESULTS: Mean age was 52.42 ± 9.42 years and 69.8% were females. The mean severity of disc herniation was 2.81 ± 1.98. The rs2272023, rs35430524, rs2882676, rs2351491, rs938609, rs3825994, rs1042630, rs698621 and rs3817428 variants and their haplotypes of ACAN were associated with the severity of lumbar disc herniation. However, only the rs35430524, rs938609 and rs3817428 variants of ACAN were detected as pathogenic by in-silico functional analysis. CONCLUSIONS: SNVs of ACAN and their haplotypes are associated with the severity of lumbar disc herniation. Functional genetic studies are necessary to identify the role of these significant SNVs in the pathogenesis of disc herniation.
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.