Journal/Magazine Articles
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This collection contains original research articles, review articles and case reports published in local and international peer reviewed journals by the staff members of the Faculty of Medicine
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Item Efficacy and safety of a novel low-dose triple single-pill combination compared with placebo for initial treatment of hypertension(Elsevier Biomedical, 2024) Rodgers, A.; Salam, A.; Schutte, A.E.; Cushman, W.C.; De Silva, H.A.; Tanna, G.L.D.; Grobbee, D.; Narkiewicz, K.; Ojji, D.B.; Poulter, N.R.; Schlaich, M.P.; Oparil, S.; Spiering, W.; Williams, B.; Jr, J.T.W.; Gutierez, A.; Sanni, A.; Lakshman, P.; McMullen, D.; Ranasinghe, G.; Gianacas, C.; Shanthakumar, M.; Liu, X.; Wang, N.; Whelton, P.BACKGROUND Single-pill combinations of 3 or more low-dose blood pressure (BP)-lowering drugs hold promise for initial or early treatment of hypertension.OBJECTIVES We conducted a placebo-controlled trial of a new single-pill combination containing low doses of telmisartan, amlodipine, and indapamide in 2 dose options to assess efficacy and safety.METHODS This international, randomized, double-blind, placebo-controlled, parallel-group trial enrolled adults with hypertension receiving 0 to 1 BP-lowering drugs. After a 2-week placebo run-in during which any BP-lowering medication was stopped, participants were eligible if home systolic BP (SBP) was 130 to 154 mm Hg. Participants were randomized in a 2:2:1 ratio to GMRx2 ¼ dose (telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg), GMRx2 ½ dose (telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg), or placebo. The primary efficacy outcome was difference in change in home SBP from randomization to week 4, and primary safety outcome was treatment discontinuation due to an adverse event.RESULTS From June 14, 2021 to October 18, 2023, a total of 295 participants (mean age: 51 years; 56% female) were randomized and 96% completed the trial. Baseline mean home BP was 139/86 mm Hg and clinic BP was 138/86 mm Hg after placebo run-in. The placebo-corrected least square mean differences in home SBP at Week 4 were -7.3 mm Hg (95% CI: -4.5 to -10.2) for GMRx2 ¼ dose and -8.2 mm Hg (95% CI: -5.2 to -11.3) for GMRx2 ½ dose; reductions for clinic BP were 8.0/4.0 and 9.5/4.9 mm Hg. At Week 4, clinic BP control (<140/90 mm Hg) was 37%, 65%, and 70% for placebo, GMRx2 ¼ dose, and GMRx2 ½ dose, respectively (both doses P < 0.001 vs placebo). Placebo, GMRx2-triple ¼, and GMRx2 ½ treatment discontinuation due to an adverse event occurred in 1 (1.6%), 0, and 6 (5.1%), respectively; out of normal range serum sodium or potassium was observed in 4 (6.3%), 12 (10.6%), and 12 (10.1%), respectively, but no participant had a serum sodium <130/>150 mmol/L or potassium <3.0/>6.0 mmol/L. Serious adverse events were reported by 2 participants in the placebo and GMRx2 ½ groups and none in the GMRx2 ¼ group.CONCLUSIONS In a population with mild-to-moderate BP elevation, both dose versions of the novel low-dose triple single-pill combination showed good tolerability and clinically relevant BP reductions compared with placebo. (Efficacy and Safety of GRMx2 Compared to Placebo for the Treatment of Hypertension: NCT04518306).Item Predictors of response to electroconvulsive therapy in major depressive disorder: A review of research findings(Springer, 2024) Baminiwatta, A.; Menon, V.PURPOSE OF REVIEW In the context of the current global move towards precision medicine, considering the adverse effects, costs and efficacy limitations of electroconvulsive therapy (ECT) in major depression, this review aimed to identify predictors of ECT response based on recent research.RECENT FINDINGS Established predictors such as older age, psychotic symptoms, melancholic features, shorter episode duration, higher baseline severity, medication failure, and comorbid personality disorder were replicated in recent studies. Genetic polymorphisms showed little utility, whereas potentially useful epigenetic predictors were identified. Neurotrophic factors offer some predictive value. Some evidence for inflammatory markers emerged. Structural neuroimaging mainly implicates the hippocampal structures, amygdala, cingulate cortex, and other frontal lobe regions. Functional neuroimaging suggests an important role of brain functional connectivity, especially involving the default mode network.SUMMARY Many previously recognized demographic and clinical predictors of ECT response were supported, but evidence for biological predictors remains largely inconclusive, and requires further exploration and replication in future research.Item Characteristics and survival of advanced untreated hepatocellular carcinoma of non-viral etiology(Indian Society of Gastroenterology, 2024) Ekanayaka, S.P.N.; Luke, N.; Thilakarathne, S.B.; Dassanayake, A.; Gunetilleke, M.B.; Niriella, M.A.; Siriwardana, R.C.INTRODUCTION AND OBJECTIVES Hepatocellular carcinoma (HCC) is an aggressive tumor and presents late. The underlying etiology of HCC is changing rapidly. HCC in Sri Lanka is unique due to its predominant non-viral etiology (nvHCC) but lacks survival data.METHOD Data was collected from patients who presented with HCC from 2011 to 2018. There were 560/568 (98.6%) nvHCC. The patients who were not candidates for tumor-specific treatment (149/560 [26.7%]) were selected. Population characteristics, demographic data, tumor characteristics, survival and factors affecting survival were analyzed.RESULTS The median age was 64 years (range 30-88) and 86% (n = 129) were males. As many as 124 (83%) were cirrhotic. The overall performance score was 80%. Nearly 21/124 tumors were detected in cirrhotic screening. Tumors were single nodular in 32 (21%), up to three nodules in 28 (18%), more than three nodules in 33 (22%) and diffusely infiltrating in 56 (37%). The major venous invasions were present in 78 (52.3%). Extra-hepatic tumor spread was seen in 19 (12.7%) (lungs 13 [72.2%], bones 2 [11.1%]). The median survival of patients receiving palliative care was three months (1-43 months). Tumor size and cirrhotic status were significant predictors in univariate analysis.CONCLUSION A quarter of nvHCCs were not amenable to treatment at presentation as they had dismal survival.Item Navigating through 65 years of insights: lessons learned on functional abdominal pain in children(Springer Verlag, 2024) Rajindrajith, S.; Boey, C.C.M.; Devanarayana, N.M.; Niriella, M.A.; Thapar, N.; Benninga, M.A.In 1958, Apley and Naish authored a groundbreaking paper in Archives of Disease in Childhood, elucidating the epidemiology and risk factors of recurrent abdominal pain in children-a subject that had confounded clinicians of their time. Surprisingly, even after 65 years, there are several unanswered questions regarding the etiology, pathophysiology, and management of pediatric abdominal pain. Contrary to the prevailing notion that children naturally outgrow functional abdominal pain, compelling evidence suggests it's possible these children develop a number of clinically significant psychological issues that could profoundly impact their quality of life and, consequently, future health and educational outcomes. In this light, we aimed to comprehensively review the current literature to update the knowledge of practicing clinicians on functional abdominal pain, summarizing the evidence from the last 65 years.Conclusion: The enduring unanswered questions surrounding childhood abdominal pain continue to challenge clinicians, resulting in unnecessary investigations, thereby contributing to substantial healthcare expenditures. It is also evident that children with long-standing symptoms would progress to adulthood with the potential to develop irritable bowel syndrome and many psychological disturbances. Several key interventions using pharmacological agents, such as amitriptyline, showed that some of these drugs are no more effective than the placebo in clinical trials. Several research during the recent past suggest that psychological interventions such as gut-directed hypnotherapy alleviate symptoms and ensure better prognosis in the long run. Therefore, clinicians and researchers must join hands to explore the pathophysiological mechanisms underpinning functional abdominal pain and novel therapeutic strategies to ensure the well-being of these children. What is Known: • Functional abdominal pain disorders are common among children, with a worldwide prevalence of 13.5% of children suffering from at least one of these disorders • These disorders contribute to a significant reduction in the quality of life of affected children and their families and lead to an array of psychological problems What is New: • The biological basis of functional abdominal pain is becoming more explicit, including complex interactions between altered microbiome, deranged motility, and psychological dysfunction with gut-brain interactions • Novel approaches giving minimal emphasis on pharmacological interventions and exploring psychological interventions are showing promising results.Item A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease(Springer, 2024) Zhang, H.; Targher, G.; Byrne, C.D.; Kim, S.U.; Wong, V.W.; Valenti, L.; Glickman, M.; Ponce, J.; Mantzoros, C.S.; Crespo, J.; Gronbaek, H.; Yang, W.; Eslam, M.; Wong, R.J.; Machado, M.V.; Yu, M.; Ghanem, O.M.; Okanoue, T.; Liu, J.; Lee, Y.; Xu, X.; Pan, Q.; Sui, M.; Lonardo, A.; Yilmaz, Y.; Zhu, L.; Moreno, C.; Miele, L.; Lupsor-Platon, M.; Zhao, L.; LaMasters, T.L.; Gish, R.G.; Zhang, H.; Nedelcu, M.; Chan, W.K.; Xia, M.; Bril, F.; Shi, J.; Datz, C.; Romeo, S.; Sun, J.; Liu, D.; Sookoian, S.; Mao, Y.; Méndez-Sánchez, N.; Wang, X.; Pyrsopoulos, N.T.; Fan, J.; Fouad, Y.; Sun, D.; Giannini, C.; Chai, J.; Xia, Z.; Jun, D.W.; Li, G.; Treeprasertsuk, S.; Li, Y.; Cheung, T.T.; Zhang, F.; Goh, G.B.; Furuhashi, M.; Seto, W.; Huang, H.; Sessa, A.D.; Li, Q.; Cholongitas, E.; Zhang, L.; Silveira, T.R.; Sebastiani, G.; Adams, L.A.; Chen, W.; Qi, X.; Rankovic, I.; Ledinghen, V.D.; Lv, W.; Hamaguchi, M.; Kassir, R.; Müller-Wieland, D.; Romero-Gomez, M.; Xu, Y.; Xu, Y.; Chen, S.; Kermansaravi, M.; Kuchay, M.S.; Lefere, S.; Parmar, C.; Lip, G.Y.H.; Liu, C.; Åberg, F.; Lau, G.; George, J.; Sarin, S.K.; Zhou, J.; Zheng, M.; Niriella, M.A. (MAFLD ICD-11 coding collaborators)BACKGROUND With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11.METHODS Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members.RESULTS A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p = 0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%).CONCLUSIONS This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.Item Mistakes in utilising histopathology for the management of liver disease(Taylor & Francis, 2024) Niriella, M.A.; Kanagarajah, D.; Hewavisenthi, J.D.S.; De Silva, H.J.INTRODUCTION Liver biopsy has become selective due to its invasiveness, potential adverse effects, patient acceptance and cost. Furthermore, the emergence of noninvasive tests (NITs) has challenged the necessity of liver biopsies in specific clinical situations. However, liver biopsy continues to play a crucial role in disease diagnosis, prognosis, and evaluating treatment compliance and response in selected patients.AREAS COVERED In this narrative review, we discuss the errors and the shortcomings that can occur at various stages, from the initial patient selection for a liver biopsy to the final reporting phase, and strategies to address them. Clinicians and pathologists must take all necessary precautions to mitigate potential shortcomings that could compromise the value of liver biopsies.EXPERT OPINION The increasing sophistication of NITs offers a safer, more convenient, and potentially more cost-effective approach to diagnosing chronic liver disease, especially for assessing the degree of liver fibrosis. As NITs continue to evolve, liver biopsy will likely transition to a more targeted role, ensuring optimal patient care in the ever-changing field of hepatology. However, liver biopsy will continue to have a pivotal role in assessing acute liver disease where the diagnostic yield of the liver biopsy still outweighs that of NITs.Item Development of a low cost semiquantitative polymerase chain reaction assay for molecular diagnosis of williams syndrome(Clinical Laboratory Publications, 2024) Ranaweera, D.M.; de Silva, D.C.; Samarasinghe, D.; Perera, S.; Kugalingam, N.; Samarasinghe, S.R.; Madushani, W.Y.; Jayaweera, H.H.E.; Gunewardene, S.; Muneeswaran, K.; Gnanam, V.S.; Chandrasekharan, N.V.BACKGROUND: Williams Beuren Syndrome (WBS) is a well-recognized and common genetic cause of congenital heart defects, developmental delay, hypercalcemia, and characteristic facial features. It is caused by a 1.5 - 1.8 Mb heterozygous deletion of chromosome 7q11.23 with loss of around 28 coding genes. The aim of this study was to develop a low-cost, semi-quantitative PCR (sqPCR) method to detect the chromosome 7q11.23 deletion. METHODS: Twenty-four suspected WBS cases were recruited following ethical clearance and informed consent. Blood was obtained, DNA extracted and spectrophotometrically quantified using standard methods. To detect the deletion by dosage analysis, a target region within a gene located in the WBS commonly deleted region of 7q11.23 was amplified together with a control region in a duplex sqPCR assay. The control region was telomeric to the WBS commonly deleted region and was located in chromosome 7q31.2. The two target regions within the deleted region namely a locus within ELN and a marker in the intergenic region between FZD9 and FKBP6 and designated IFF, were amplified in separate duplex sqPCR assays. The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene was used as the control for normalization. Included in the assay were a non-deleted and deleted individuals' samples. RESULTS: Nineteen patients were identified to have the deletion while five did not. All 24 patients' results were confirmed by whole exome sequencing and 11 also by fluorescence in-situ hybridization (FISH). CONCLUSIONS: The data obtained indicates the sqPCR assay developed in this study to be an accurate and reliable diagnostic test for WBS. Most Sri Lankan patients with WBS are diagnosed clinically, as many parents of affected WBS children are unable to afford currently available molecular diagnostic testing. This low cost sqPCR test is therefore likely to benefit Sri Lankan WBS patients, by enabling genetic testing for confirming or refuting a clinical diagnosis of WBS and may be of use in other low and middle income countries.Item Suicide among psychiatrists: From healers to seekers of mental health care(Elsevier, 2024) Shoib, S.; Saeed, F.; Ahmed, S.; Park, C.; Roza, T.H.; Nazari, S.K.; Armiya'u, A.Y.; Berardis, D.; Mahesar, R.A.; Chandradasa, M.Addressing suicide and mental health issues among psychiatrists, particularly during a crisis such as the COVID-19 pandemic is important. several factors contribute to this risk, such as long duty hours, burnout, emotional exhaustion, exposure to secondary trauma, and the impact of the pandemic on the mental health of healthcare workers. This paper emphasizes the urgent need for interventions at individual and organizational levels to address burnout and mental health issues among psychiatrists. Supporting the mental resilience of mental health professionals will improve the mental health of the community.Item Exploring clinical reasoning in child language assessment through decoloniality(Taylor & Francis Group, 2024) Samaraweera, B.P.; Pillay, M.; Muttiah, N.; Moodley, L.PURPOSE: Clinical reasoning has been taught, practised, and researched under Western epistemologies, which have been fallible in addressing the complexity of clinical reasoning within Indigenous cultures and societies. We explored how speech-language pathologists in Sri Lanka negotiate and value Indigenous and Western perspectives in clinical reasoning within a decolonial framework. METHOD: This study used participatory research methodology within the decolonised qualitative research paradigm to produce data collaboratively with eight Sri Lankan speech-language pathologists. Oral history narratives and object-based textual reflections generated the necessary data for the study. Systematic visual-textual analysis and reflexive thematic analysis were carried out iteratively, and the data analysis and interpretation were undertaken collaboratively with the participants. RESULT: We generated four key themes about professional education, individuality in practice, holistic thinking, and balancing interests and priorities. The results demonstrate that social, political, and economic forces impact practitioners' clinical reasoning. CONCLUSION: Practising science in its original form within Indigenous contexts is challenging. Colonial roots and imperialism impact the delivery of appropriate services in socially and politically marginalised communities. Practitioners' self-awareness about authentic identities and practical wisdom can develop culturally relevant knowledge for equitable practice.Item A rare case of abrupt onset vascular lump in the newborn; neonatal kaposiform haemangioendothelioma(Batticaloa Medical Association, 2023) Dayasiri, K.; de Abrew, G.; Samaraweera, S.; Thadchanamoorthy, V.