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Hypertension (HTN) is recognized as a major modifiable risk factor for cardiovascular deaths in South Asia. Our aim was to furnish a comprehensive analysis of HTN prevalence, trends, control efforts, awareness, barriers in care delivery and associated factors, based on nationally derived evidence in Sri Lanka. A systematic search of online databases ( PubMed, Web of Science, Scopus ), local journals and repositories yielded 6704 results, of which 106 were included. Prevalence of HTN steadily increased from 23.7% (2005-2006) to 34.8% (2021). Associated factors identified were hyperhomocysteinaemia [odds ratio (OR) 2.80], overweight/obesity (OR 2.02), perceived job stress (OR 2.20-3.02), physical inactivity (OR 2.08-2.80), salt intake more than 5 g/day (OR 2.50), smoking (OR 2.31) and waist-to-height ratio more than or equal to 0.5 (OR 2.23). Cohort studies revealed poor blood pressure control and treatment adherence among patients. Pharmacological ( n  = 4) and nonpharmacological ( n  = 6) interventional studies were few. Studies on knowledge, attitudes and practices demonstrated a lack of public awareness. Despite the high prevalence of HTN in Sri Lanka, many cases remain undiagnosed, underscoring importance of targeted screening programmes and culture-specific public health education programmes., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction and Importance: Bile duct adenoma (BDA) is a rare benign liver neoplasm, with relatively few cases reported in literature., Case Presentation: A 55-year-old man diagnosed with symptomatic gallstone disease who underwent elective laparoscopic cholecystectomy. During the procedure, there were multiple liver nodules mimicking hepatic metastases. Histological examination and contrast-enhanced computed tomography (CECT) of the liver confirmed the diagnosis of BDA., Discussion: When incidental liver nodules are encountered intraoperatively, thorough evaluation is essential to confirm the diagnosis. Structured approach using histological examination and imaging (CECT of the liver/ MRI) confirmed the diagnosis of BDA., Conclusions: BDA is a rare benign liver neoplasm that can be challenging to differentiate from hepatocellular carcinoma or liver metastases. Accurate identification of BDA can prevent overtreatment or mismanagement., Competing Interests: Declaration of competing interest The Author(s) declares(s) that there is no conflict of interest., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Context: Functional abdominal pain disorders (FAPDs) are debilitating disorders with unknown current prevalence., Objective: To estimate global prevalence rates of FAPDs, their entities, and variations by diagnostic criteria, geography, gender, and age., Data Sources: Medline, Embase, CINAHL, PsycInfo, and Cochrane Library were searched through October 14, 2024., Study Selection: Epidemiological studies of birth cohorts, school based, and from general population samples reporting FAPD prevalence in children (aged 4-18 years) using the Rome criteria., Data Extraction: Two researchers independently performed screening, data extraction, and quality assessment., Results: A total of 66 studies, encompassing 201 134 participants from 29 countries, were included. The estimated global pooled prevalence of FAPDs was 11.7% (95% CI, 10.5%-13.1%). The most prevalent type was irritable bowel syndrome (5.8%; 95% CI, 4.5-7.4%), while functional abdominal pain-not otherwise specified was least prevalent (1.2%; 95% CI, 0.7%-2.1%)). Prevalence was highest using Rome III (13.2%; 95% CI, 11.3%-15.3%) and lowest under Rome IV criteria (9.0%; 95% CI, 6.7%-12.0%; P = .05). Girls had higher prevalence (14.4%; 95% CI, 12.5%-16.6%) than boys (9.4%; 95% CI, 7.8%-11.4%; P < .01). FAPDs were nonsignificantly more prevalent in Asia (13.0%; 95% CI, 10.4%-16.3%) compared to Europe (8.3%; 95% CI, 6.4%-10.7%) and North America (7.7%; 95% CI, 4.3-13.6; P = .09). No differences by age (P = .14) were recorded. Contributing factors include anxiety, depression, stress, negative life events, and poor sleep., Limitations: Language restrictions, significant interstudy heterogeneity, and underrepresentation from Africa., Conclusions and Relevance: FAPDs affect over 1 in 9 children worldwide, with higher prevalence in girls and those with psychological stressors., (Copyright © 2025 by the American Academy of Pediatrics.)

The immunogenicity of rabies vaccines is commonly measured by serological testing, which includes measuring rabies virus-neutralising antibody titre levels in the serum. Apart from humoral immunity, cellular immunity measurements are also helpful in assessing the immunogenicity and efficacy of rabies vaccinations. Recently, there has been an increased emphasis on cellular immunity measurements against rabies in humans and animals. This review aimed to systematically analyse the literature on the composition of cellular immune responses against rabies vaccination in laboratory dogs. A literature survey was conducted to collect suitable articles by searching the research databases PubMed, Web of Science and Scopus. Subsequently, a two-person screening was conducted to identify suitable articles based on predetermined inclusion and exclusion criteria. Data extraction was performed by two authors independently. A total of 1396 studies were identified from the initial search. Following the screening, six studies were selected for final review. Different methods of detecting immune parameters from peripheral blood mononuclear cells were identified from the studies. Reports have demonstrated positive outcomes of the use of adjuvants for cellular immunity development. Even though the lack of specific immunological techniques and the specific reagents have negatively affected these types of cellular immunity measurements, it was evident that combining both humoral and cellular immune parameters against the rabies antigen would provide a clearer picture of the level of responsiveness in animals towards vaccinations and the protection against the disease. The protocol for this review was published in the International Prospective Register of Systematic Review (CRD42022380023)., Competing Interests: Declaration of conflicting interestsThe author(s) declares no conflict of interest with respect to the research, authorship and/or publication of this article.

Homocystinuria due to cystathionine beta-synthase (CBS) deficiency is a rare metabolic disorder inherited as an autosomal recessive trait. Spectrum of genetic variants in CBS gene and their correlation with the phenotypes of homocystinuria in Sri Lankan patients have not been reported to date. The objective of this study was to identify the genotypes and genotype-phenotype correlations in a cohort of Sri Lankan patients with homocystinuria due to CBS deficiency. We determined the variants in CBS gene in 14 Sri Lankan patients with homocystinuria, from 9 unrelated families. The clinical features and the biochemical response to pyridoxine were studied for further correlations. Among the 14 patients, the common clinical features were ectopia lentis (100%), intellectual disability (92%) and marfanoid features (78%) at presentation while three of them had developed osteoporosis (21%). Median age at diagnosis was 8 years (range 2-12). Three pathogenic variants (c.1006C>T, c.785C>T and c.19del) and two likely pathogenic variants (c.869C>T, c.772G>A) in CBS gene were identified. Thirteen patients with homozygous genotypes were non-responsive to pyridoxine while the only patient with the compound heterozygous genotype (c.869C>T/c.772G>A) responded to pyridoxine treatment. The genotypic spectrum observed in Sri Lankan patients is unique and mostly associated with pyridoxine non-responsiveness. The majority of the patients were identified clinically at a later stage of the disease due to lack of a screening programme in the country. Therefore, it is important to improve the awareness of the disease among the clinicians in the interest of early diagnosis and early commencement of metabolic treatment., Competing Interests: The authors declare no conflicts of interest., (© 2025 The Author(s). JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.)

Background: Communication boards are a low-technology tool used to facilitate interactions with mechanically ventilated patients in intensive care units (ICUs). Research on the acceptability of communication boards in resource-limited intensive care settings is lacking., Aim: The aim of this study was to assess patients' and nurses' experienced acceptability of implementing a communication board in Sri Lankan ICUs., Design: This was a cross-sectional substudy of the intervention group patients and nurses who participated in a pilot randomised controlled trial that assessed the feasibility of implementing a communication board in two ICUs in one Sri Lankan hospital., Methods: In the parent trial conscious, ventilated adult ICU patients were recruited. This substudy included all patients in the intervention group in the parent trial and ICU nurses who used the communication board. Sekhon's generic acceptability questionnaire, adapted and translated into Sinhala, was administered to both patients and nurses. The questionnaire comprised eight items; seven items represented the seven constructs of the framework (possible scores ranging from 7 to 35), and a single item measured general acceptability. Descriptive and inferential statistics were used to analyse the data. Additionally, nurses were asked three open-ended questions regarding their views on using the communication board, and data were analysed using content analysis., Results: Of the 123 patients screened in the parent trial, 60 met the inclusion criteria and were randomised, with 30 randomly allocated to the intervention group. In total, 30 patients and 50 nurses completed the survey (response rate: 100%). Both patients and nurses rated all items positively except "burden". Patient and nurse total mean scores for the seven items, excluding the single-item general acceptability, were 27.5 (standard deviation: 2.6) and 27.2 (standard deviation: 2.2), respectively. Patients and nurses both scored high on the single-item general acceptability, with a median (interquartile range) of 4.0 (4.0-5.0) and 4.0 (4.0-4.0), respectively. Two patient items and five nurse items significantly correlated with the single-item general acceptability. Two categories, (i) drivers for using the communication board and (ii) obstacles to communication board use, were found through content analysis., Conclusion: This substudy demonstrated that the communication board was acceptable to both patients and nurses despite its perceived "burden"., Competing Interests: Declaration of competing interests The authors have no conflict of interest to declare., (Copyright © 2024 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Link Samahan® (LS), a product of Link Natural Products (Pvt) Limited, Sri Lanka contains extracts of 14 medicinal plants. It is used as a prophylactic against cold and cold related symptoms. It has immunomodulatory activity, specifically enhancing the humoral immune response., Objective: To investigate the anti-inflammatory activity (AIA) of LS and related mechanisms., Materials and Methods: In vivo AIA was assessed by the inhibition of carrageenan-induced rat paw-edema. Mechanisms of AIA were assessed in vitro by the inhibition of reactive oxygen species (ROS) and reactive nitrogen species (RNS) production and expression of inducible nitric oxide synthase (iNOS) gene using rat peritoneal cells., Results: LS showed an increasing inhibition in rat paw-edema up to 5 h compared to the biphasic pattern exhibited by the reference drug, Indomethacin. Inhibition by LS at the 1 st and 3 rd -5 th hours (44.7% and 73.0-74.6%) was comparable to indomethacin (47.4% and 83.6-76.5%; p > 0.05) whereas at the 2 nd hour, LS exhibited a significantly higher inhibition compared to indomethacin (66.7% vs 28.6%; p < 0.05). LS treatment significantly inhibited the ROS (superoxide; 47.2 ± 0.86%; p < 0.05) and RNS (nitrite; 54.0 ± 0.40%; p < 0.05) production in rat peritoneal cells. Further, specific inhibition of iNOS gene expression in rat peritoneal cells resulted in a significant reduction in RNS production whereas LS had lesser or no inhibitory effect on endothelial NOS and neuronal NOS gene expression., Conclusion: LS has potent anti-inflammatory activity and selective inhibition of iNOS activity. AIA of LS shown here supports its use as a prophylactic against cold and cold related symptoms., Competing Interests: Conflict of interest Ajita Mahendra Abeysekera is an advisor to Link Natural Products (Pvt) Ltd. Other authors declare that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Hypertension is the leading preventable cause of cardiovascular morbidity and mortality globally, with a disproportionate impact on low-income and middle-income countries like Sri Lanka. Effective blood pressure (BP) control improves outcomes in patients with hypertension. This study aimed to assess the prevalence of uncontrolled hypertension, and its correlates among Sri Lankan patients with hypertension in clinic settings., Methods: A cross-sectional study was done at the largest tertiary care hospital in Sri Lanka and patients with hypertension presenting to its medical clinics over a 6-month period were recruited. An interviewer-administered questionnaire captured sociodemographic, morbidity, and medication details from records. BP measurements were taken following standard guidelines with OMRON-X7 BP monitors. Multivariate logistic regression was used to identify significant associations ( P  < 0.05)., Results: Among 600 patients (mean age 64 ± 9 years, 43% men), 55% had uncontrolled hypertension. Most (62%) were on 1 or 2 antihypertensives, primarily renin-angiotensin blockers (91%), with minimal (<10%) thiazide use. Uncontrolled hypertension was less common among furosemide (10.5%) and spironolactone (21.5%) users but frequent among those on alpha-blockers (16.3%). Coronary artery disease (58%), heart failure (9%), and stroke (17%) were more common in men and those with longstanding hypertension. Beta-blockers were favoured in those with cardiac comorbidities, and dihydropyridines in those with stroke. Potential treatment resistance, seen in 11%, was associated with increased cardiac morbidity, while sociodemographic factors and family history had no significant impact on BP control or cardiovascular morbidity., Conclusion: Uncontrolled hypertension and cardiovascular morbidity were highly prevalent. The data suggest the need for optimized antihypertensive regimens, with reduced use of alpha-blockers and early and prioritized incorporation of diuretics., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate the feasibility of implementing a communication board in intensive care units in terms of participant recruitment and retention, intervention fidelity, and ability to collect patient outcome data., Design: A prospective, two-arm, unblinded, pilot randomised controlled trial., Research Methodology: Adult, conscious, mechanically ventilated intensive care patients were recruited between August and November 2023. All participants received routine communication practices; the intervention group also received the communication board. Prior to the study, all nurses were trained on using the communication board. Patient or proxy consent was obtained. Data were collected from patients, nurses, patients' medical records, and screening, tracking, intervention fidelity, and contamination logs., Main Outcome Measures: The primary outcome data was feasibility of participant recruitment, retention, and intervention fidelity, which was recorded daily until seven days of follow-up or pre-defined trial endpoints. Secondary patient outcomes (anxiety, satisfaction, ease of communication) were assessed at recruitment and approximately 24 h after recruitment or soon after extubation, whichever occurred first., Setting: Two intensive care units in one Sri Lankan tertiary care hospital., Results: Of the 123 patients, 60 (75.0%) were recruited and randomised (30 control; 30 intervention). All intervention group patients received the communication board (100% intervention fidelity), and 58 (96.7%) completed the follow-up. On recruitment, 12.5% of secondary patient outcome data was missing, and 9.9% on follow-up, predominantly associated with the 10-item ease of communication scale., Conclusions: Conducting a larger, definitive communication board trial is feasible but collecting secondary patient outcome data, especially ease of communication was challenging. Study procedures need to be refined prior to a larger trial., Implications for Clinical Practice: The use of communication boards in intensive care units may improve patient-centred care for ventilated patients but requires further, high quality effectiveness trials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: The authors report no conflict of interest.

A 68-year-old woman, after an Indian cobra (Naja naja) bite, developed anaphylaxis, Takotsubo cardiomyopathy, and Kounis syndrome. She was initially diagnosed with acute coronary syndrome after anaphylaxis due to exposure to cobra venom, indicating Kounis syndrome. The echocardiogram, electrocardiogram, and almost complete reversal of dyskinetic myocardium established Takotsubo cardiomyopathy. Adrenaline, initially given for anaphylaxis, and noradrenaline as an intravenous infusion for hypotension potentially precipitated the ATAK complex. The diagnosis was established by history, low blood pressure, elevated troponin, numerous dyskinetic segments in the echocardiogram, and normal coronary vessels in the angiogram., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Apis dorsata stings are amongst the most frequent insect-stings in Sri Lanka. A. dorsata venom consists of a mixture of components including PLA 2 , melittin, hyaluronidase and apamin. However, there are no studies done in Sri Lanka to evaluate the environmental influence in venom production. We, herein, tried to correlate the variations in those four venom components of A. dorsata with environmental factors (temperature, rainfall, wind speed and relative humidity). The venom components were analyzed using high-performance liquid chromatography (HPLC) and variations in environmental factors were gathered from the Department of Meteorology, Sri Lanka. Of the four components, PLA 2 (r = 0.718; p = 0.009 and r = 0.636; p = 0.026) and melittin r = 0.734; p = 0.007 and r = 0.582; p = 0.047) showed significant correlations with temperature and wind speed, respectively. Whilst relative humidity showed significant negative correlations with PLA 2 (r = - 0.634; p = 0.027) and melittin (r = -0.643; p = 0.024). There was no significant correlation of climatic parameters with hyaluronidase or apamin. The results indicated a variation in the composition of venom components with the month in which the venom was collected due to climatic influence and it should be considered when therapeutic grade venom preparations are produced., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Rajiva de Silva reports financial support was provided by National Science Foundation, Sri Lanka. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: We declare no competing interests.

This report summarizes the key findings of a workshop undertaken at the International Child Neurology Congress in 2024 by child neurologists with expertise in training education and invested colleagues. The workshop aimed to explore global issues which have impact on access to child neurology training. The major findings supported a great need for more training programs globally, that consensus is needed for the minimum standards of training, and that training programs can be strengthened via global health partnerships especially with collaborations from regions with more available resources. The group concurred that the phenomena of 'neurophobia' amongst general paediatricians and medical trainees, was a reality, and creates barriers both working with paediatric colleagues, as well as recruiting specialists to the field. Optimal teaching practices for child neurology should include the expansion of learning through global partnerships and virtual educational resources. Measures must be put into place for fledgling training programs, to support colleagues in less resourced settings and to avoid their burn-out. Collegial and collaborative work is essential to support the future of child neurology across the globe, both to reach the current capacity needs but also to meet the necessary growth in the field., Competing Interests: Declaration of competing interest The authors have declared no conflict of interest for the submitted manuscript on “Report from the Child Neurology Education and Training Workshop at the International Child Neurology Congress 2024: Expert's Addressing the Training Gap”., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective. The introduction of automatic tube current modulation (ATCM) has resulted in complex relationships between scanner parameters, patient body habitus, radiation dose, and image quality. ATCM adjusts tube current based on x-ray attenuation variations in the scan region, and overall patient dose depends on a combination of factors. This work aims to develop mathematical models that predict CT radiation dose and image noise in terms of attenuating diameter and all relevant scanner parameters. Approach. A homogenous phantom, equipped with the features to conduct discrete and continuous adaption tests, was developed to model ATCM in a Philips CT scanner. Scanner parameters were varied based on theoretical dose relationships, and a MATLAB script was developed to extract data from DICOM images. R statistical software was employed for data analysis, plotting, and regression modelling. Main Results. Phantom data provided the following insights: Median tube current decreased by 81% as tube potential varied from 80 kVp to 140 kVp. Doubling the DoseRight Index (DRI) from 12 to 24, at 24 cm diameter, produced a 294% increase in mA and a 46% decrease in noise. Mean mA increased by 53% whilst mean noise increased by 5.7% as helical pitch increased from 0.6 to 0.925. Changing rotation time from 0.33s to 0.75s gave a 56% reduction in mean mA and no change in image noise. Increasing detector collimation ( n × T ) resulted in higher tube currents and lower output image noise values, as n and T were varied independently. Interpreting these results to apply transformations relevant to each independent variable produced models for tube current and noise with adjusted R-squared values of 0.965 and 0.912, respectively. Significance. The models developed more accurately predict radiation dose and image quality for specific patients and scanner settings. They provide imaging professionals with a practical tool to optimize scan protocols according to patient diameters and clinical objectives., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

The south Asian region (SAR) is home to 1·74 billion people, corresponding to 22% of the global population. The region faces several challenges pertaining to changing epidemiology, rapid urbanisation, and social and economic concerns, which affect health outcomes. Primary health care (PHC) is a cost-effective strategy to respond to these challenges through integrated service delivery, multi-sectoral action, and empowered communities. The PHC approach has historically been an important cornerstone of health policy in SAR countries. However, the region is yet to fully reap the benefits of PHC-oriented health systems. Our introductory paper in this Lancet Series on PHC in the SAR describes the existing PHC delivery structure in five SAR nations (ie, Bangladesh, India, Nepal, Pakistan, and Sri Lanka) and critically appraises PHC performance to identify its enablers and barriers. The paper proposes investing in a shared culture of innovation and collaboration for revitalisation of PHC in the region., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Refractory hypothyroidism is associated with high morbidity and increased healthcare expenditure. In general, the use of the levothyroxine absorption test looks promising in evaluating refractory hypothyroidism but has shown significant variability in protocols in multiple settings. We intended to assess the usefulness of the levothyroxine absorption test in a low-resource setting and to assess the factors associated with refractory hypothyroidism. A cross-sectional study among age-matched 25 cases of refractory hypothyroidism and 24 treatment-responsive hypothyroid controls was conducted. A supervised levothyroxine absorption test was performed with levothyroxine 1000 μg tablets after a 10-h fast, and serum free tetraiodothyronine (FT4) levels were measured at 0, 1, 2, 3, 4, and 5 h. Descriptive statistics, chi-square test, Student's t-test, and logistic regression were used in the analysis. Results showed no significant difference in age, body weight, etiology of hypothyroidism, interfering medications, thyroxine storage, and ingestion technique in cases and controls. Cases had a longer duration of hypothyroidism and males had a higher peak FT4 concentration. During pooled analysis, serum FT4 peaked at 3 h with an increment of 149.4% (128.4-170.5%) from baseline and plateaued thereafter. The absolute value of FT4 at 3 h was 41.59 (s.d. 14.14) pmol/L (3.23 ng/dL). We concluded that there was no significant difference in the pattern of levothyroxine absorption in both groups. The most common cause of refractory disease was pseudo-malabsorption. Rapid supervised levothyroxine absorption test with two blood samples for FT4 at baseline and at the peak of absorption (3 h) is simple, convenient, and cost-effective, particularly in low-resource settings.

Information disorder is problematic in health because it can limit effective treatment options and preventive measures. Interviews were conducted to understand the current policies and practices better. The qualitative analysis resulted in three broad thematic areas, with 115 codes and 12 code groups. Since Sri Lanka is a low- to middle-income country, optimising available resources is crucial; alternative cost-free tools and freely accessible international standards and guidelines can be customised to meet the country's needs.

A method for separating M. oryzae from rice samples infected with multiple pathogens using basic laboratory equipment is described. We conducted a series of experiments to obtain a single spore of M. oryzae. This method can also be used to isolate spores from other fungal species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose of the study: The study aimed to develop and validate a holistically based follow-up pain assessment diary for patients with cancer pain in Sri Lanka. Design of the study: Mixed-method design adapted. Methods used: Developing a pain diary and testing its psychometric qualities were done in two phases. Comprehensive literature research and qualitative semistructured interviews with patients, clinical, and subject specialists created the pain diary items. Content, face, construct, criterion validity, and reliability were evaluated. Findings: The essential domains to be assessed were identified under six main categories; pain and related characteristics, physical, psychological, social, spiritual, and financial aspects. The average variance extracted from the subscales "Influence on daily life," "Gastric disturbances," and "Pain intensity" were 0.526, 0.562, and 0.696, respectively. The heterotrait-monotrait criterion values between subscales were from 0.691 to 0.44, which was lower than the threshold. Good to excellent correlation coefficients were demonstrated with the scores of reference tools. Cronbach's alpha was computed for each subscale and ranged from 0.75 to 0.92 and composite reliability from 0.921 to 0.826. Conclusions: Pain diary is a reliable and valid instrument for follow-up assessment of holistic pain experience enabling holistic nursing among patients with cancer pain in Sri Lanka.

Background: Vitamin D deficiency (VDD) is conventionally associated with inadequate sunlight exposure. Ironically, recent evidence suggests a rising prevalence in urban areas of tropical regions like Sri Lanka, where comprehensive data are unavailable. This study aimed to estimate the prevalence of low vitamin D status in urban adults and its impact on serum calcium., Methods: A population-based cross-sectional study was conducted among 1260 adults aged 35-74 years, living in Colombo, the most urban district in Sri Lanka. They were recruited from 63 administrative divisions, using multi-stage, probability-proportionate-to-size, cluster sampling. Non-fasting venous blood was collected without tourniquet. Low vitamin D (< 30.0 ng/mL), VDD (< 20 ng/mL) and vitamin D insufficiency (20.0-29.9 ng/mL) were determined using chemiluminescence assay method, and serum calcium using Calcium Gen2 reagent., Results: Among the population (53.3% females; mean age = 51.8 years), the prevalence of low vitamin D was 93.9% (95% CI: 92.5-95.2). This was primarily due to VDD (67.5%; 95% CI: 64.9.0-70.1%), with some insufficiency (26.4%; 95% CI: 24.0-28.9%). Most VDD cases (53.9.0%) were 'mild' (10.0- < 20.0 ng/mL) in severity, with fewer 'moderate' (12.8%) and 'severe' (0.8%) cases. Prevalence of VDD was highest in females, aged 35-44-years, living in 'highly urban' areas and of Tamil ethnicity. Further, VDD showed a decreasing trend with older age groups, while it was significantly more prevalent in females than males (72.6% vs. 61.7%; p < 0.01), across all age groups. Low serum calcium levels were observed in 9.8% of adults with low vitamin D, compared to 22.4% with normal vitamin D, implying that there could be factors other than vitamin D in maintaining serum calcium levels., Conclusions: Colombo District, representing urban settings in Sri Lanka faces a high prevalence of low vitamin D, primarily VDD, with higher rates in females, younger individuals and highly urban areas. These findings challenge assumptions about tropical regions being guaranteed of optimal vitamin D levels; and underscore the need for national vitamin D supplementation and food fortification programs, especially in high-risk urban settings in South Asian countries like Sri Lanka., (© 2024. The Author(s).)

Competing Interests: We declare no competing interests. ZCS and AI are staff members of the World Health Organization. They themselves alone are responsible for the views expressed in the article, which do not necessarily represent the views, decisions, or policies of the World Health Organization.

High-resolution melt (HRM) analysis is a closed-tube technique for detecting single nucleotide polymorphisms (SNPs). However, it has limited use in high-resolution melting devices, even those with high thermal accuracy (HTA). In addition to the cost of switching to these specialized devices, the presence of nearest neighbour neutral changes (class III, IV SNPs and small indels) made HRM-based assays a challenging task due to reduced sensitivity. This study aimed to design a common modified competitive amplification of differently melting amplicons (CADMA)-based assay to address these challenges by generating allele-specific qPCR products that are detectable on most qPCR platforms. For this study, SNPs were selected from all four classes of SNPs (class I: C/T or G/A mutation; class II: C/A or G/T mutation; class III: G/C mutation; class IV: A/T mutation). A single base pair and 19 bp indels were also chosen to simulate how CADMA primers could be designed for indels of varying lengths. The melting temperatures (Tm) were determined using IDT oligoAnalyzer. qPCR and melt data acquisition were performed on the CFX96 qPCR platform, and the melt curve data were analyzed using Precision Melt software (Bio-Rad, USA). The clusters for different genotypes were successfully identified with the aid of the control samples, and Tm predictions were carried out using the uMelt batch and Tm online tools for comparison. Using HRM-qPCR assays based on the modified CADMA method, genotyping of various SNPs was successfully carried out. For some SNPs, similarly shaped melt curves were observed for homozygotes and heterozygotes, making shape-based genotype prediction difficult. The Tm values calculated via the Blake and Delcourts (1998) method were the closest to the experimental Tm values after adjusting for the salt concentration. Since HRM assays usually depend on the ΔTm caused by mutations, they are prone to a high error rate due to nearest neighbour neutral changes. The technique developed in this study significantly reduces the failure rates in HRM-based genotyping and could be applied to any SNP or indel in any platform. It is crucial to have a deep understanding of the melt instrument, its accuracy and the nature of the target (SNP class or indel length and GC content of the flanking region). Furthermore, the availability of controls is essential for a high success rate., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Melioidosis is caused by community-acquired gram-negative bacillus Burkholderia pseudomallei which resides in soil and water. It was first described in 1912 in Burma and 1927 in Sri Lanka. Melioidosis presents with non-specific clinical and biochemical findings. Diagnosis is confirmed by the isolation of bacteria in cultures or demonstrating antibody response. Once the diagnosis is made, patients are managed with a course of intravenous antibiotics followed by a long course of oral antibiotics. Even with antibiotic treatments, most patients do not achieve complete recovery which results in chronic disease. Prolonged antibiotic therapy makes patients less compliant with treatment. Here we present a 50-year-old Sri Lankan male with diabetes mellitus presented with low-grade fever and back pain. He was found to have multiple abscesses involving the liver, spleen and left psoas muscle. Initially, he was evaluated for tuberculosis and later only melioidosis was diagnosed. The patient was managed with guided aspiration of abscesses and intravenous antibiotics. Subsequently, the patient defaulted on all treatments. It is important to consider melioidosis as a differential diagnosis in immunocompromised patients presented with multiple abscesses. It is important to maintain a registry for follow-up melioidosis patients to prevent becoming chronic melioidosis patients and to save healthcare costs., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Objectives: To explore patients' and nurses' views of potential facilitators, barriers, and prospective acceptability of implementing a communication board in Sri Lankan intensive care units., Design: A qualitative, descriptive study., Research Methodology: Eight patients who received mechanical ventilation and nine nurses who worked in adult medical and surgical intensive care units were purposively selected. Data were collected via audio-taped, semi-structured, face-to-face interviews in January/February 2023. Interview guide questions were informed by the knowledge-to-action framework and the theoretical framework of acceptability. Data were analysed using inductive and deductive content analysis. The 32-item checklist of the consolidated criteria for reporting qualitative research (COREQ) was used to ensure the quality of reporting., Setting: A 3,000 bed Sri Lankan teaching hospital with 18 intensive care units., Findings: Four categories reflecting patients' and nurses' anticipated use of the board were found. The first category described patients' and nurses' 'readiness to use the communication board' and their positive attitudes towards it. The second category focused on the 'potential benefits of the communication board', while the third category emphasised the 'individual patient characteristics' that should be taken into consideration when implementing communication boards. The final category described practical aspects related to 'integrating communication boards into routine practice'., Conclusion: This study demonstrates communication boards may improve communication between ventilated patients and nurses, and they are acceptable to end users. Adopting these tools may be a pivotal step to enhancing patient-centred care in demanding intensive care settings., Implications for Clinical Practice: An inability to communicate effectively with ventilated intensive care patients creates negative experiences for both patients and nurses. Communication boards may act as a medium to better understand patients' needs during mechanical ventilation.Understanding patients' and nurses' views is beneficial when designing patient-centred communication interventions in intensive care units., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Compared to the West, suicide prevention in the Southeast Asian (SEA) region is challenging due to resource constraints, a relatively greater contribution of social compared to psychological factors, and low levels of general awareness coupled with high stigma around suicide and mental illness. Collaboration and knowledge sharing are essential to circumvent these challenges. The Partnerships for Life (PfL) initiative of the International Association of Suicide Prevention aims to enhance knowledge sharing, foster collaboration between nations, and support the development and implementation of evidence-informed approaches to suicide prevention. In February 2024, the SEA region of the PfL conducted the first regional workshop on suicide prevention, in which representatives from 10 out of 12 SEA nations participated. In this paper, we outline the key priorities, challenges, strengths, and opportunities for suicide prevention in the region with a view to inform resource-effective suicide prevention strategies that have optimal utility and uptake., Competing Interests: Declaration of Competing Interest LV is the regional coordinator of the International Association for Suicide Prevention’s Partnerships for Life initiative for the Southeast Asian region. VM and AVC are regional co-coordinators for the Partnerships for Life initiative for the Southeast Asian region Other authors declare no conflicts of interest relevant to the contents of the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Obscure gastrointestinal bleeding represents about 5% of all gastrointestinal haemorrhages which is characterized by continuous or recurrent bleeding from an undetermined source after an initial bidirectional endoscopy. Meckel's diverticulum is a rare but recognized cause of obscure gastrointestinal bleeding. A carefully selected line of investigations is paramount to localize the causative lesion in obscure gastrointestinal bleeding which is a challenge in subacute cases. We present a case of 35-year-old female with thalassemia minor and mild anaemia presented with acute gastrointestinal bleeding from the ectopic pancreatic mucosa of an Meckel's diverticulum where only a small focus of gastric tissue was identified histologically during the follow-up. This case discusses the rarity of this histological presentation of Meckel's diverticulum as obscure gastrointestinal bleeding and the importance of intraoperative decision-making and intraoperative enteroscopy in cases of obscure gastrointestinal bleeding when other tests are negative., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2024.)

Morbidity management of filarial lymphedema remains a challenge even during the post-lymphatic filariasis elimination era in Sri Lanka despite provision of the predominantly hygiene-based WHO Essential Package of Care. Because prior studies have suggested that 6 weeks of doxycycline may reduce progression of limb lymphedema, we conducted a randomized, placebo-controlled, superiority study to evaluate this possibility in Sri Lanka. Patients aged 14 to 65 years with lymphedema in one or both legs received either 200 mg of doxycycline daily for 6 weeks or matching placebo. The primary efficacy endpoint was improvement or lack of progression in lymphedema stage at 24 months postenrollment. Secondary endpoints included change in lymphedema stage at 12 and 24 months, frequency of acute adenolymphangitis episodes, and perceived disability measured by the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0). Training and supplies for limb hygiene were provided throughout the study. Two hundred participants (100 in each arm) with lymphedema of Dreyer stages 1 to 3 were enrolled. By the end of the 2-year study, 29% of the doxycycline patients and 34% of those on placebo showed improvement (i.e., a decrease in lymphedema stage), whereas 11% and 15% of the two groups showed worsening of the lymphedema. Adenolymphangitis rates were comparable in the two groups (43 doxycycline and 38 placebo recipients), although attacks lasted slightly longer in placebo patients (6.5 days versus 5.2 days). In both groups, perceived disability improved initially, with partial rebound in the second year. Only 34 adverse events affecting 24 patients (11%) occurred during the 6-week treatment period. Although doxycycline did not significantly impact lymphedema progression in this study, the results clearly indicate that clinical and personal benefits can be obtained from intensive hygiene management alone.

Objective: Diagnostic role of autoantibodies (AAb) as serological biomarkers has not been specifically investigated in laryngeal cancer (LC) previously. The study investigates the presence of anti-LC AAbs and their potential as a biomarker for early diagnosis of LC, to improve patient outcome., Method: Anti-LC AAb levels were investigated in LC patients (n = 30) and healthy individuals (n = 30) by indirect enzyme-linked immunosorbent assay (ELISA). Patient AAb levels were analyzed with various clinical factors, primarily tumor stage., Results: AAb levels were significantly higher in LC patients than in the control group (P = .019). The diagnostic performance of AAb-level testing for LC detection presented a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 70% each. The positive likelihood (LR+) and negative likelihood (LR-) ratios were 2.33 and 0.43, respectively. AAb levels were independent of cancer stage (P = .708), duration since first appearance of symptoms (P = .228), duration of medical attention (P = .231), and degree of risk-factor exposure (P = .478)., Conclusion: Significant level of AAbs could be detected among LC patients with good diagnostic performance, irrespective of stage. Thus, anti-LC AAbs reflect potential to be utilized as predictive biomarkers in early diagnostics of LC., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: Addressing the challenge of cost-effective asthma diagnosis amidst diverse symptom patterns among patients, this study aims to develop a machine learning-based asthma prediction tool for self-detection of asthma. Methods: Data from 6,665 participants in the Sri Lanka Health and Ageing Study (2018-2019) are used for this research. Thirteen machine learning algorithms, including Logistic Regression, Support Vector Machine, Decision Tree, Random Forest, Naïve Bayes, K-Nearest Neighbors, Gradient Boost, XGBoost, AdaBoost, CatBoost, LightGBM, Multi-Layer Perceptron, and Probabilistic Neural Network, are employed. Results: A hybrid version of Logistic Regression and LightGBM outperformed other models, achieving an AUC of 0.9062 and 79.85% sensitivity. Key predictive features for asthma include wheezing, breathlessness with wheezing, shortness of breath attacks, coughing attacks, chest tightness, nasal allergies, physical activity, passive smoking, ethnicity, and residential sector. Conclusion: Combining Logistic Regression and LightGBM models can effectively predict adult asthma based on self-reported symptoms and demographic and behavioural characteristics. The proposed expert system assists clinicians and patients in diagnosing potential asthma cases., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr S.K. is a scientific consultant for George Clinical. Dr V.C.-S. is a speaker and consultant from Baxter Brazil. Dr S.S. has received an education grant from Amgen Canada. The rest of the authors have no relevant disclosures.

Ethnopharmacological Relevance: In vitro and in vivo studies have shown anti-viral and immunomodulatory actions in components of many traditional medicines. Various constituents of traditional medicines have been found to be effective against coronavirus disease (COVID-19) in several clinical trials and in-silico studies. Sudarshana cúrna, a polyherbal Ayurvedic medicine, has been used over thousands of years for a variety of infectious fevers., Aims of the Study: This study aimed to evaluate the efficacy and safety of Link Natural Sudarshana (LNS) tablets, in patients with COVID 19 disease. LNS is a polyherbal preparation comprising 49 medicinal plants included in the Sudarshana cúrna., Materials and Methods: A randomized parallel-group double-blind placebo-controlled multi-center phase II clinical trial was conducted in patients with mild to moderate COVID-19 disease. They were randomly allocated to intervention and control groups. The intervention group received LNS tablets whereas the control group received placebo tablets for 10 days or until the patient was discharged from the hospital. All patients received standard symptomatic treatment. The primary outcome, a reduction in mean log viral load was assessed at day 5 of treatment. The secondary outcomes, clinical progression and safety, were assessed by, monitoring changes in symptoms daily on a Likert scale ranging from 1 to 4 and laboratory tests respectively., Results: A total of 171 patients (treatment group 83, control group 88) completed the trial. There were no significant differences between the baseline status of the two groups except that body mass index was significantly higher in the placebo group. The mean log viral load reduction at day 5 was higher in the treatment group (2.20 ± 1.67) compared to the placebo group (1.93 ± 1.80), with a mean difference of -0.278. This difference was not statistically significant at the 5% significant level. Reduction of mean cumulative symptom score, which included 16 symptoms graded according to severity, was higher in the treatment group compared to the placebo group. This difference was not statistically significant. None of the study participants developed hypoxia. Among the 7 lymphopenia patients in the placebo group, 3 continued to have lymphopenia at day 10, whereas 9 lymphopenia patients in the treatment group, reverted to normal counts. C reactive proteins (CRP) showed a greater reduction in the treatment group. None reported adverse effects. No significant changes occurred in hematological and biochemical parameters that assessed safety., Conclusions: LNS is safe to use in COVID-19 patients and accelerated the decline in viral load, relieved symptoms, reduced CRP levels and reversed lymphopenia earlier, when compared to the placebo., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Colvin Goonaratna and Jennifer Perera are consultants to Link Natural Products (Pvt) Ltd for clinical trials., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The National Epilepsy Center (NEC) in Sri Lanka was established in 2017. Seizure outcome, effects on quality of life (QOL) and surgical complications among nonpediatric patients who underwent epilepsy surgery from October 2017 to February 2023 are described., Methods: Nineteen patients (≥14 years) underwent epilepsy surgery at the NEC. We used Engel classification and Quality of Life in Epilepsy 31 (QOLIE-31) questionnaire to assess seizure outcome and QOL respectively. Surgical complications were categorized into neurological and complications related to surgery., Results: Nine female and 10 male patients underwent surgery (mean age 27.5 years (range 14-44 years). The mean follow-up duration was 10.5 months (range 6-55 months). Twelve patients underwent temporal lobe resections. At 6-months follow-up, 83.3% (10/12) had favorable seizure outcomes with Engel class I/II. At 1-year follow-up 6/8 patients (75.0%) and at 2-year follow-up, 5/7 patients (71.4%) had a favorable outcome. Seven patients had extra-temporal lobe surgeries and one defaulted. Seizure freedom was observed in 6/6 at 6 months, 3/3 at 1-year, and 2/2 at 2-year follow-up. Five patients (26.3%) experienced minor post-operative surgical site infection. Two (11.1%) had persistent quadrantanopia. Meaningful improvement in QOL (change in QOLIE-31 score ≥11.8) was observed irrespective of seizure outcome or type of surgery (P < 0.001)., Conclusions: Epilepsy surgery is effective in developing countries. Seizure outcomes in our patients are comparable to those worldwide. Clinically important QOL improvement was observed in our series. This is the first published data on epilepsy surgery outcomes in nonpediatric patients from Sri Lanka., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In Sri Lanka, several tea grades are produced in factories located in different agro-climatic regions within three geographical elevations. The study aimed to determine the microbial quality of different tea grades and composite tea samples obtained from factories situated at diverse locations. The average APC, yeast & mould counts and coliforms in different tea grades ranged from 3.4 × 10 3 to 2.0 × 10 4  cfu/g, 4.8 × 10 2 to 2.5 × 10 3  cfu/g and 0.005 to 3.9 × 10 1 Most Probable Number (MPN)/g respectively. The tea samples collected from different factories had mean values of APC and yeast & mould as 5.3 × 10 3 ±1.3 × 10 3  cfu/g and 9.7 × 10 2 ±1.9 × 10 2  cfu/g. Escherichia coli ( E.coli ) and Salmonella were not detected either in tea grades or in composite samples. The identified microorganisms in tea samples belong to phyla Firmicutes, Proteobacteria, Ascomycota, Basidiomycota and Zygomycota. The samples collected from the mid country elevation had the highest counts of APC and yeast & mould counts were high in the low country elevation. More than 70 % of the tested samples comply with the SLTB guidelines given for the microbiological quality of black tea. The distribution of bacterial, yeast and mould and coliform densities of tea were significantly variable with respect to geographic areas., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:S. H. S. Karunaratne reports financial support was provided by Sri Lanka Treasury. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Hyponatraemia is an uncommon complication of external biliary drainage. We report on a 62-year-old male with hilar cholangiocarcinoma who developed refractory severe hyponatraemia despite sodium replacement during preoperative external biliary drainage. Nasojejunal bile refeeding restored sodium levels to normal., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Introduction: Field midwives (FMs) in Sri Lanka, who care for women and children, were challenged during the COVID-19 pandemic. During COVID-19, the majority of research found that healthcare professionals experienced anxiety and depression., Objective: This study examined anxiety, depression, and related factors among FMs during the COVID-19 pandemic in Sri Lanka., Methods: A descriptive cross-sectional approach was used with 145 FMs from randomly selected Medical Officer of Health (MOH) areas in the Matara district. The data were collected by an interviewer-administered questionnaire containing the Generalized Anxiety Disorder-7 and Patient Health Questionnaire-9 tools. Descriptive statistics, chi-square test, and logistic regression examined and presented the data., Results: Among the participants, 54.5%, 31.0%, 8.3, and 6.2% experienced minimal, mild, moderate, and severe anxiety. Whereas 46.2%, 32.4%, 17.2%, 1.4%, and 2.8% of the participants had no or minimal, mild, moderate, moderately severe, and severe depression. Being in a family of COVID-19-infected family members, relatives, or friends (OR = 0.33, p = 0.018) and being in a nuclear family (OR = 0.47, p = 0.033) were found to be risk factors against depression while having a history of chronic diseases (OR = 5.87, p = 0.002) and having a sufficient amount of personal protective equipment (OR = 2.52, p = 0.041) were found to be protective. Similarly, having a history of chronic diseases (OR = 4.89, p = 0.002) was found to be protective against anxiety., Conclusion: The majority of FMs had minimal anxiety and depression during the COVID-19 pandemic. The results will be valuable in formulating policies to support the psychological health of FMs in Sri Lanka., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Tuberculosis is a leading cause of death worldwide, especially in developing countries. It can affect any site in the body and have a myriad of presentations making diagnosis challenging. Tuberculous lymphadenitis in the abdomen is rare. We present a case of a 42-year-old man who presented with non-specific abdominal symptoms and was found to have an intraabdominal abscess on computed tomography scan of the abdomen. Endoscopic ultrasound-guided aspiration was performed, and tuberculosis was confirmed. This case highlights the importance of having a high clinical suspicion of tuberculosis even with vague symptoms in tuberculosis endemic countries. This would prevent unnecessary surgery as tuberculosis is responsive to anti-tuberculosis drugs., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background and Objectives: Spinal muscular atrophy (SMA) is a neurodegenerative disorder manifesting with progressive muscle weakness and atrophy. SMA type 1 used to be fatal within the first 2 years of life, but is now treatable with therapies targeting splicing modification and gene replacement. Nusinersen, risdiplam, and onasemnogene abeparvovec-xioi improve survival, motor strength, endurance, and ability to thrive, allowing many patients to potentially attain a normal life; all have been recently approved by major regulatory agencies. Although these therapies have revolutionized the world of SMA, they are associated with a high economic burden, and access to these therapies is limited in some countries. The primary objective of this study was to compare the availability and implementation of treatment of SMA from different regions of the world., Methods: In this qualitative study, we surveyed health care providers from 21 countries regarding their experiences caring for patients with SMA. The main outcome measures were provider survey responses on newborn screening, drug availability/access, barriers to treatment, and related questions., Results: Twenty-four providers from 21 countries with decades of experience (mean 26 years) in treating patients with SMA responded to the survey. Nusinersen was the most available therapy for SMA. Our survey showed that while genetic testing is usually available, newborn screening is still unavailable in many countries. The provider-reported treatment cost also varied between countries, and economic burden was a major barrier in treating patients with SMA., Discussion: Overall, this survey highlights the global inequality in managing patients with SMA. The spread of newborn screening is essential in ensuring improved access to care for patients with SMA. With the advancement of neurotherapeutics, more genetic diseases will soon be treatable, and addressing the global inequality in clinical care will require novel approaches to mitigate such inequality in the future., Competing Interests: V.D. Armengol reports no disclosures relevant to the manuscript; B.T. Darras reports grants and non-financial support from, and being the FIREFISH Study Steering Committee Chair and an ad hoc scientific advisory board member for Roche/Genentech, which manufactures risdiplam, grant support from and being an ad hoc scientific board member for Biogen, which manufactures nusinersen; non-financial support from and being an ad hoc scientific board member for Novartis Gene Therapies (AveXis), which manufactures onasemnogene abeparvovec, grant support for the ENDEAR, CHERISH, and CS2/CS12 studies from Ionis Pharmaceuticals, grants from and being an ad hoc scientific board member for Sarepta Pharmaceuticals, grants from PTC Therapeutics, Fibrogen, Summit, the US NIH and National Institute of Neurological Disorders and Stroke, Slaney Family Fund for SMA, Spinal Muscular Atrophy Foundation, CureSMA, and Working on Walking Fund, being an ad hoc scientific board member for Vertex, and a data and safety monitoring board member for Amicus Inc; A.A. Abulaban reports no disclosures relevant to the manuscript; A. Alshehri reports no disclosures relevant to the manuscript; N. Barišić is investigator for Roche clinical trials, served as advisor or consultant, speaker or member of Advisory Boards for: Roche, Novartis, PTC, and Biogen/Medis-Adria; T. Ben-Omran reports no disclosures relevant to the manuscript; G. Bernert has served on Advisory boards for Avexis/Novartis Gene Therapies, Biogen, PTC, Roche, Pfizer and Santhera, he has received funding for travel or speaker honoraria for Biogen, Novartis, Pfizer, PTC, Roche, Santhera, and Merz, he has served as PI for DELOS, SIDEROS (SANTHERA), LELANTOS 1 + 2 (Fibrogen), and STRIDE Registry (PTC); C. Castiglioni has participated in advisory and educational activities by Biogen, Roche and Novartis and received honoraria for these activities; Y.H. Chien has served on advisory boards for Biogen and Novartis Gene Therapies and received honoraria for educational activities; M.A. Farrar is funded by a National Health and Medical Research Council of Australia Investigator grant (APP1194940), she has served on advisory boards for Biogen, Roche and Novartis Gene Therapies and received honoraria for educational activities; G. Kandawasvika reports no disclosures relevant to the manuscript; S. Khadilkar reports no disclosures relevant to the manuscript; J.K. Mah received research grants as PI in studies sponsored by Biogen, Roche, and the Alberta Children's Hospital Foundation; C. Marini-Bettolo reports participation in Scientific Advisory boards and teaching initiatives for Avexis, Biogen, and Roche, she is involved as an investigator in clinical trials from Avexis, and she is principal investigator for the UK SMA patient registry funded by SMA UK; D. Osredkar reports participation in scientific advisory boards and teaching initiatives for Biogen, Medis, Novartis Gene Therapies, PTC, Roche, and Serapta, and he is PI in studies sponsored partly by Biogen and PTC; G. Pfeffer reports no disclosures relevant to the manuscript; F. Piazzon reports no disclosures relevant to the manuscript; I. Pitarch-Castellano has participated in advisory and educational activities by Biogen, Roche and Novartis; S. Quijano-Roy is PI for clinical trials of Biogen (DEVOTE), Novartis Gene Therapies (SMART), and Roche (OLEOS), has served on advisory boards for Biogen, Novartis GT and Roche, and has received travel and speaker honoraria from Biogen Novartis and Roche; K. Saito is funded by the Practical Research Project for Rare/Intractable Diseases of the Japan Agency for Medical Research and Development, AMED (grant number: 22ek0109472h0003), and she is Principal Investigator for clinical trials of Biogen (DEVOTE), Novartis Gene Therapies, Inc./Novartis (SPR1NT, LT-002), and Chugai (Roche) (SUNFISH), has served on advisory boards for Biogen, Novartis Gene Therapies, Inc./Novartis, and Chugai (Roche), and has received honoraria from Biogen, Novartis and Chugai; J.H. Shin reports no disclosures relevant to the manuscript; J.F. Vázquez-Costa is funded by grants of the Instituto de Salud Carlos III (JR19/00030, PI Vázquez), served on advisory boards for Biogen and Roche and received travel and speaker honoraria from Biogen and Roche; M.C. Walter has served on advisory boards for Avexis, Biogen, Novartis, Roche, Santhera, Sarepta, PTC Therapeutics, Ultragenyx, Wave Sciences, received funding for Travel or Speaker Honoraria from Novartis, Biogen, Ultragenyx, Santhera, PTC Therapeutics, and worked as an ad hoc consultant for AskBio, Audentes Therapeutics, Biogen Pharma GmbH, Fulcrum Therapeutics, Novartis, PTC Therapeutics, Roche; J. Wanigasinghe receives support as principal investigator from NIH grant 1R21HD093563-01; H. Xiong is one of the investigators of Biogen (DEVOTE), Roche (FIREFISH, SUNFISH) and Novartis (STEER), but has no conflicts of interest related to this study; R.C. Griggs serves as Co-PI of a training grant from the NINDS for the Experimental Therapeutics of Neurological Diseases. He receives grant funding from the NIH, the Muscular Dystrophy Association, and the Parent Project for Muscular Dystrophy in support of clinical trials, and he also receives support from PTC Therapeutics, Sarepta Pharmaceuticals and Santhera Pharmaceutics for clinical trial data, and he serves as Chair of a DSMB for Solid Pharmaceuticals, Chair of the Research Advisory Committee of the American Brain Foundation, inaugural Chair of the American Academy of Neurology Section on Experimental Neurotherapeutics, and he receives compensation as an Editor of Cecil Textbook of Medicine; B. Roy has served as a consultant for Alexion Pharmaceuticals (now part of AstraZeneca), Takeda Pharmaceuticals, and argenx, but he has no conflicts directly related to this work. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp. TAKE-HOME POINTS → Stark global disparities in access to disease-modifying therapy (DMT) for spinal muscular atrophy (SMA) currently exist, and these disparities are not driven simply by differences in countries' wealth.→ The economic burden of DMT was identified by a majority of survey respondents as a barrier to treatment of SMA, with several other barriers also noted.→ Most respondents reported access to genetic testing, but newborn screening is unavailable in several countries included in this survey and is only implemented regionally in others.→ Increased awareness of unequal access to treatment is the first step toward mitigating inequities in rare neurologic diseases., (© 2023 American Academy of Neurology.)

Flaviviruses such as dengue, Zika, and West Nile viruses are highly concerning pathogens that pose significant risks to public health. The NS1 protein is conserved among flaviviruses and is synthesized as a part of the flavivirus polyprotein. It plays a critical role in viral replication, disease progression, and immune evasion. Post-translational modifications influence NS1's stability, secretion, antigenicity, and interactions with host factors. NS1 protein forms extensive interactions with host cellular proteins allowing it to affect vital processes such as RNA processing, gene expression regulation, and cellular homeostasis, which in turn influence viral replication, disease pathogenesis, and immune responses. NS1 acts as an immune evasion factor by delaying complement-dependent lysis of infected cells and contributes to disease pathogenesis by inducing endothelial cell damage and vascular leakage and triggering autoimmune responses. Anti-NS1 antibodies have been shown to cross-react with host endothelial cells and platelets, causing autoimmune destruction that is hypothesized to contribute to disease pathogenesis. However, in contrast, immunization of animal models with the NS1 protein confers protection against lethal challenges from flaviviruses such as dengue and Zika viruses. Understanding the multifaceted roles of NS1 in flavivirus pathogenesis is crucial for effective disease management and control. Therefore, further research into NS1 biology, including its host protein interactions and additional roles in disease pathology, is imperative for the development of strategies and therapeutics to combat flavivirus infections successfully. This Review provides an in-depth exploration of the current available knowledge on the multifaceted roles of the NS1 protein in the pathogenesis of flaviviruses.

Aim: Pharmacogenomics is emerging in South Asia, including Sri Lanka, with potential to optimize drug therapy and reduce adverse effects. This review evaluates the state of pharmacogenomics research in Sri Lanka, emphasizing population-specific factors to guide future advancements. Materials & methods: A literature search was performed across PubMed/Web-of-Science/SciVerse-Scopus/Embase, and Sri Lanka Journals Online, along with searches for relevant theses in local health repositories/university databases. Studies were categorized into clinical correlational, descriptive or novel assay development studies. Results: Eleven published articles and eight theses were included. One study examined somatic variants ( KRAS gene), while all others focused on germline variants. There were two clinical correlational studies: tamoxifen adverse effects and CYP2D6 variants and FTO gene rs9939609 variants and weight gain caused by second-generation antipsychotics. Eight descriptive studies evaluated prevalence of CYP2D6 variants, HLA-B*15:02 allele, KRAS gene mutations and variants related to statin, warfarin and anticancer drug metabolism. Additionally, nine studies developed, validated and tested novel assays for detecting key pharmacogenomically important variants. Conclusion: While pharmacogenomics research in Sri Lanka has made strides, more clinical studies and broader genomic research are needed. Overcoming challenges related to funding, public awareness and regional collaboration is essential to advance personalized medicine and improve therapeutic outcomes in Sri Lanka and South Asia.