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Abstract Objective Falls take a high priority among the prevalent medical conditions in old age. Despite this, a history of falls or the risk of future falls is not routinely assessed or properly managed in medical clinics in Sri Lanka. This study was done to evaluate the prevalence and factors associated with falls and recurrent falls among older adults attending medical clinics in four selected tertiary care centres in the country. Methods A cross-sectional study was carried out at four centres (Teaching Hospital Karapitiya, Colombo South Teaching Hospital, Colombo North Teaching Hospital and University Hospital-Kotelawala Defence University) with 704 older adults, aged 65 years and above, attending medical clinics for more than six consecutive months. Information related to falls and possible associated factors (socio-demographic, behavioural, environmental and biological) were collected using an interviewer-administered questionnaire. Results The Mean (SD) age of the participants was 72.5(5.5) years and 58.7% were females. Of the 704 total sample, 220 (31.3%, 95% CI 28–35%) participants experienced at least one fall after the age of 65, and 12.8% (95% CI 10–15%) (n = 90) experienced recurrent falls (two or more falls within the last 12 months). Falls were associated with gender, level of education, marital status, and physical dependence (p

Abstract Background Parental history of diabetes is an established risk factor for type 2 diabetes mellitus (T2DM). There is limited data on the association of parental history with the prevalence of T2DM in Sri Lanka. The study aims to examine the prevalence and correlation of parental history and factors such as the onset age, glycaemic control, and self-reported dietary compliance among T2DM patients. With a rising incidence of T2DM in Sri Lanka, understanding the impact of parental history on age at diagnosis and glycemic control can aid in targeted screening and interventions. Methods A cross-sectional study was carried out on 500 T2DM patients attending a diabetes clinic in Galle, the capital of Southern Sri Lanka with a multiethnic population. Convenient sampling strategy was followed in the recruitment process and a questionnaire-based method was used to collect the data. All the collected data was analysed using SPSS V 25.0. Results 51.2% had a parental history of T2DM, and those with a positive parental history were diagnosed six years earlier than those with a negative parental history (p

Abstract Background Population aging is a significant social problem in the twenty first century. Recent economic and social changes lead increasing number of elders to spend their lives in elderly homes. Institutionalized elders have to face many physical and psychological problems which negatively impact their quality of life. Geriatric depression (GD), catastrophizing pain (CP) and sleep disorders (SD) are some common problems among them. Methods Present study was designed to assess the prevalence of GD, CP and SD and their correlations in institutionalized elders. A descriptive cross-sectional study was conducted in elderly homes (n = 20) in the Galle district of Sri Lanka enrolling 310 subjects. GD, CP and SD were assessed using validated Sinhala versions of Geriatric Depression Scale (GDS), Pain Catastrophizing Scale (PCS) and Pittsburgh Sleep Quality Index (PSQI) respectively. Data were analyzed using SPSS version 25.0 for windows by using descriptive statistics, the Pearson’s chi-square test and Pearson’s bivariate correlation (p

Abstract Background Historically, geneticists have relied on genotyping arrays and imputation to study human genetic variation. However, an underrepresentation of diverse populations has resulted in arrays that poorly capture global genetic variation, and a lack of reference panels. This has contributed to deepening global health disparities. Whole genome sequencing (WGS) better captures genetic variation but remains prohibitively expensive. Thus, we explored WGS at “mid-pass” 1-7x coverage. Results Here, we developed and benchmarked methods for mid-pass sequencing. When applied to a population without an existing genomic reference panel, 4x mid-pass performed consistently well across ethnicities, with high recall (98%) and precision (97.5%). Conclusion Compared to array data imputed into 1000 Genomes, mid-pass performed better across all metrics and identified novel population-specific variants with potential disease relevance. We hope our work will reduce financial barriers for geneticists from underrepresented populations to characterize their genomes prior to biomedical genetic applications.

Abstract Objective Current guidelines on rectal cancer (RC) management recommend pre-operative MRI for loco-regional staging and CT for staging of metastases. This allows appropriate selection of patients for chemo-radiotherapy (CRT). However, MRI is not freely available in many low-income countries. We assessed the status of pre-operative imaging for RC in Sri Lanka and evaluated the performance of CT in RC staging. Results A pre-tested interview-administered questionnaire was used to assess the pre-operative use of MRI and CT in RC. CT findings from 37 RC patients were then compared with histopathology findings. Of the 64 surgeons interviewed, 57 (89.1%) did not request an MRI for their RC patients. Reasons cited included limited availability and long waiting times due to competing health needs. A CT was requested by all. In RC, the overall accuracy of CT for T staging was 43.2% and 29.7% of T1–T2 tumours were over-staged as T3. The overall accuracy of CT for regional lymph node staging was 70.3%. In summary, CT alone is not suitable for RC staging in any setting. It leads to over-staging and patients may thus receive unnecessary CRT. Steps must be taken to improve access to pre-operative MRI among Sri Lankan RC patients.

Abstract Background Chronic Kidney Disease - Mineral and Bone Disorder (CKD-MBD) is a significant cause of morbidity among haemodialysis patients and is associated with pathological changes in phosphate, calcium and parathyroid hormone (PTH). In the ACTIVE Dialysis study, extended hours dialysis reduced serum phosphate but did not cause important changes in PTH or serum calcium. This secondary analysis aimed to determine if changes in associated therapies may have influenced these findings and to identify differences between patient subgroups. Methods The ACTIVE Dialysis study randomised 200 participants to extended hours haemodialysis (≥24 h/week) or conventional haemodialysis (≤18 h/week) for 12 months. Mean differences between treatment arms in serum phosphate, calcium and PTH; and among key subgroups (high vs. low baseline phosphate/PTH, region, time on dialysis, dialysis setting and frequency) were examined using mixed linear regression. Results Phosphate binder use was reduced with extended hours (− 0.83 tablets per day [95% CI -1.61, − 0.04; p = 0.04]), but no differences in type of phosphate binder, use of vitamin D, dose of cinacalcet or dialysate calcium were observed. In adjusted analysis, extended hours were associated with lower phosphate (− 0.219 mmol/L [− 0.314, − 0.124; P

Abstract Background Acetyl xylan esterase plays an important role in the complete enzymatic hydrolysis of lignocellulosic materials. It hydrolyzes the ester linkages of acetic acid in xylan and supports and enhances the activity of xylanase. This study was conducted to identify and overexpress the acetyl xylan esterase (AXE) gene revealed by the genomic sequencing of the marine bacterium Ochrovirga pacifica. Results The AXE gene has an 864-bp open reading frame that encodes 287 aa and consists of an AXE domain from aa 60 to 274. Gene was cloned to pET-16b vector and expressed the recombinant AXE (rAXE) in Escherichia coli BL21 (DE3). The predicted molecular mass was 31.75 kDa. The maximum specific activity (40.08 U/mg) was recorded at the optimal temperature and pH which were 50 °C and pH 8.0, respectively. The thermal stability assay showed that AXE maintains its residual activity almost constantly throughout and after incubation at 45 °C for 120 min. The synergism of AXE with xylanase on beechwood xylan, increased the relative activity 1.41-fold. Conclusion Resulted higher relative activity of rAXE with commercially available xylanase on beechwood xylan showed its potential for the use of rAXE in industrial purposes as a de-esterification enzyme to hydrolyze xylan and hemicellulose-like complex substrates.

Abstract Background The increasing prevalence of type 2 diabetes and suboptimal glycaemic control in Kuwait requires novel, wide-reaching, low-cost interventions to motivate and mobilise individuals towards more effective self-management. More than 2 million people in Kuwait own mobile phones. We will test whether automated personalised health text messages based on principles of motivational interviewing and are responsive to biodata delivered remotely is potentially effective in improving glycaemic control compared to usual care. Methods This is a two-arm parallel single-blind randomised controlled trial of 572 individuals with type 2 diabetes in Kuwait. We will develop a culturally appropriate database of text messages supporting positive lifestyle changes in type 2 diabetes. A computer programme will deliver over 400 text messages over a 12-month period using algorithms which provide participants with information on diet and physical activity as well as personalised messages regarding motivators to change behaviours. Individuals aged 18–75 years with established type 2 diabetes who are fluent in Arabic or English and officially resident in Kuwait will be identified via screening of hospital diabetes clinic and primary care practices and invited to participate. A sample of 572 participants will be randomised to usual care or usual care plus the DATES text message intervention. Randomisation will be conducted by an independent Clinical Trials Unit and researchers collecting baseline and outcome data will be blinded to treatment allocation. The primary outcome is change in HbA1c and weight at 12 months in both study arms. Secondary outcomes will include changes in physical activity, fasting lipids and quality of life in both study arms. Discussion The potential of mobile phones in improving diabetes self-care in settings with a high prevalence of diabetes and widespread mobile phone usage has face validity. Mobile phones and text messaging are an understudied virtual communication media which can deliver discrete focused psychological support to motivate and enable diabetes self-care changes. Trial registration ISRCTN10342151. 11/03/2015.

Abstract Background People with type 1 diabetes who attend structured education training in self-management using flexible intensive therapy achieve improved blood glucose control and experience fewer episodes of severe hypoglycaemia. However, many struggle to sustain these improvements over time. To inform the design of more effective follow-up support we undertook a review of qualitative studies which have identified factors that influence and inform participants’ self-management behaviours after attending structured education and their need for support to sustain improvements in glycaemic control. Methods We undertook a meta-ethnography of relevant qualitative studies, identified using systematic search methods. Studies were included which focused on participants’ experiences of self-managing type 1 diabetes after attending structured education which incorporated training in flexible intensive insulin therapy. A line of argument approach was used to synthesise the findings. Results The search identified 18 papers from six studies. The studies included were judged to be of high methodological quality. The line of argument synthesis developed the Follow-Up Support for Effective type 1 Diabetes self-management (FUSED) model. This model outlines the challenges participants encounter in maintaining diabetes self-management practices after attending structured education, and describes how participants try to address these barriers by adapting, simplifying or personalising the self-management approaches they have learned. To help participants maintain the skills taught during courses, the FUSED model presents ten recommendations abstracted from the included papers to provide a logic model for a programme of individualised and responsive follow-up support. Conclusions This meta-ethnography highlights how providing skills training using structured education to people with type 1 diabetes does not necessarily result in participants adopting and sustaining recommended changes in behaviour. To help people sustain diabetes self-management skills after attending structured education, it is recommended that support be provided over the longer-term by appropriately trained healthcare professionals which is responsive to individuals’ needs. Although developed to inform support for people with type 1 diabetes, the FUSED model provides a framework that could also be applied to support individuals with other long term conditions which require complex self-management skills to be learned and sustained over time. Trial registration PROSPERO registration: CRD42017067961.

Abstract Background Quantification of toxic trace metals in biota is very important to monitor both ecosystem health and public health. Stomopneustes variolaris is a widespread species of sea urchin in the world that have edible gonads that are in high demand. This study attempted to examine the levels of accumulated toxic trace metals and their relationship between the test diameter and the gonad weight of the black sea urchin (S. variolaris) in Sri Lanka. Results As S. variolaris is highly abundant in southwest coast of Sri Lanka, three sampling sites were selected in this region (Mount-Lavinia, Beruwala and Tangalle). The concentration of toxic trace metals (Hg, Cd, Pb and As) in the gonads of S. variolaris was determined in randomly selected subset from the above samples. The levels of above metals in gonads did not exceed the permitted standard levels of the EU and Sri Lanka. The mean size and weight of S. variolaris collected from Mount-Lavinia was 5.55 ± 1.04 cm and 101.40 ± 57.76 g, respectively; for Beruwala it was 6.54 ± 0.86 cm and 147.90 ± 50.40 g, respectively, and for Tangalle it was 6.41 ± 1.05 cm and 150.50 ± 59.45 g respectively. There was a significant relationship between all the analysed trace metals and the test diameter and gonad weight of S. variolaris in Sri Lanka. Conclusions This study revealed that the trace metal levels in gonads of S. variolaris did not exceed the harmful level for human consumption.

Abstract Background Randomised controlled trials (RCTs) of complex interventions often begin with a pilot phase to test the proposed methods and refine the intervention before it is trialled. Although the Medical Research Council (MRC) recommends regular communication between the practitioners delivering the intervention and the researchers evaluating it during the pilot phase, there is a lack of practical guidance about how to undertake this aspect of pre-trial work. This paper describes a novel structured process for collaborative working, which we developed to iteratively refine a complex intervention prior to an RCT. We also describe an in-built qualitative study to learn lessons about how this approach could be used by future study teams. Methods This work forms part of a broader research programme to develop and trial a complex intervention for people with type 1 diabetes, called DAFNEplus. The intervention is being piloted in three National Health Service (NHS) diabetes centres in two waves, with refinements being incrementally implemented between each wave in response to real-time, collective learning (combining practitioner experience, process evaluation data and patient and public involvement via an advisory group). A structured ‘Collaborative Working Group’ (CWG) process, comprising monthly teleconferences and four strategically timed face-to-face meetings, is being used to identify and respond systematically to emerging implementation challenges and research findings. The group involves 25 members of the study team, including the multi-disciplinary practitioners delivering the intervention, the research teams conducting the process evaluation, the study manager and Chief Investigator. An in-built qualitative study comprising documentary analysis of meeting materials, discourse analysis of meeting transcripts, reflexive note taking, and thematic analysis of focus groups and interviews with CWG members is being undertaken to explore how the CWG works and how its processes and procedures might be improved. Discussion The CWG process offers a potential model for collaborative working in future pre-trial pilot phases and intervention development studies that operationalises MRC guidance to progressively develop a complex intervention and foster shared ownership through genuine collaboration. The findings from the qualitative study will provide insight into how to best support collaborative working to achieve optimal intervention design.

Abstract Background Between 2011 and 2013, global and national guidelines for preventing mother-to-child transmission (PMTCT) of HIV shifted to recommend Option B+, the provision of lifelong antiretroviral treatment for all HIV-infected pregnant women. Methods We aimed to analyse how Option B+ reached the policy agenda, and unpack the processes, actors and politics that explain its adoption, with a focus on examining UNICEF’s contribution to these events. Analysis drew on published articles and other documentation, 30 key informants interviews with staff at UNICEF, partner organisations and government officials, and country case studies. Cameroon, India, South Africa and Zimbabwe were each visited for 5–8 days. Interview transcripts were analysed using Dedoose software, reviewed several times and then coded thematically. Results A national policy initiative in Malawi in 2011, in which the country adopted Option B+, rather than existing WHO recommended regimens, irrevocably placed the policy on the global agenda. UNICEF and other organisations recognised the policy’s potential impact and strategically crafted arguments to support it, framing these around operational considerations, cost-effectiveness and values. As ‘policy entrepreneurs’, these organisations vigorously promoted the policy through a variety of channels and means, overcoming concerted opposition. WHO, on the basis of scanty evidence, released a series of documents towards the policy’s endorsement, paving the way for its widespread adoption. National-level policy transformation was rapid and definitive, distinct from previous incremental policy processes. Many organisations, including UNICEF, facilitated these changes in country, acting individually, or in concert. Conclusions The adoption of the Option B+ policy marked a departure from established processes for PMTCT policy formulation which had been led by WHO with the support of technical experts, and in which recommendations were developed following shifts in evidence. Rather, changes were spurred by a country-level initiative, and a set of strategically framed arguments that resonated with funders and country-level actors. This bottom-up approach, supported by normative agencies, was transformative. For UNICEF, alignment between the organisation’s country focus and the policy’s underpinning values, enabled it to work with partners and accelerate widespread policy change.

Abstract Background Competencies in psychological techniques delivered by primary care nurses to support diabetes self-management were compared between the intervention and control arms of a cluster randomised controlled trial as part of a process evaluation. The trial was pragmatic and designed to assess effectiveness. This article addresses the question of whether the care that was delivered in the intervention and control trial arms represented high fidelity treatment and attention control, respectively. Methods Twenty-three primary care nurses were either trained in motivational interviewing (MI) and cognitive behavioural therapy (CBT) skills or delivered attention control. Nurses’ skills in these treatments were evaluated soon after training (treatment arm) and treatment fidelity was assessed after treatment delivery for sessions midway through regimen (both arms) using the Motivational Interviewing Treatment Integrity (MITI) domains and Behaviour Change Counselling Index (BECCI) based on consultations with 151 participants (45% of those who entered the study). The MITI Global Spirit subscale measured demonstration of MI principles: evocation, collaboration, autonomy/support. Results After training, median MITI MI-Adherence was 86.2% (IQR 76.9–100%) and mean MITI Empathy was 4.09 (SD 1.04). During delivery of treatment, in the intervention arm mean MITI Spirit was 4.03 (SD 1.05), mean Empathy was 4.23 (SD 0.89), and median Percentage Complex Reflections was 53.8% (IQR 40.0–71.4%). In the attention control arm mean Empathy was 3.40 (SD 0.98) and median Percentage Complex Reflections was 55.6% (IQR 41.9–71.4%). Conclusions After MI and CBT skills training, detailed assessment showed that nurses had basic competencies in some psychological techniques. There appeared to be some delivery of elements of psychological treatment by nurses in the control arm. This model of training and delivery of MI and CBT skills integrated into routine nursing care to support diabetes self-management in primary care was not associated with high competency levels in all skills. Trial registration ISRCTN75776892; date registered: 19/05/2010.

Abstract Background Chronic abdominal pain is a common worldwide problem and known to be associated with psychological problems. This study evaluated the association between abdominal pain-predominant functional gastrointestinal disorders (AP-FGIDs), psychological maladjustment and personality traits in adolescents. Methods Adolescents aged 13–18 years were recruited from 5 randomly selected schools in Ampara district of Sri Lanka. AP-FGIDs were diagnosed using Rome III criteria. Translated and validated Rome III questionnaire (Child report form), personality questionnaire (PAQ) and PedsQL (Pediatric Quality of Life) inventory were used in data collection. Written consent was obtained from a parent and assent was obtained from every child recruited. The questionnaire was distributed in an examination setting to ensure confidentiality and privacy. Research assistants were present during data collection to assist on any necessary clarifications. Results A total of 1697 subjects were recruited [males 779 (45.9%), mean age 15.1 years, SD 1.6 years]. AP-FGIDs were present in 202 (11.9%). Those with AP-FGIDs had significantly higher mean scores for all personality traits (hostility and aggression, negative self-esteem, emotional unresponsiveness, emotional instability and negative world view), except dependency. Affected children had lower scores for all 4 domains of HRQoL (physical, emotional, social and school functioning), compared to controls (p

Abstract Background Group B Streptococcus (GBS) is the leading cause of neonatal sepsis in the developed world. Little is known about its epidemiology in the developing world, where the majority of deaths from neonatal infections occur. Maternal carriage of GBS is a prerequisite for the development of early onset GBS neonatal sepsis but there is a paucity of carriage data published from the developing world, in particular South East Asia. Methods We undertook a cross sectional study over a 13 month period in a remote South East Asian setting on the Thai-Myanmar border. During labour, 549 mothers had a combined vaginal rectal swab taken for GBS culture. All swabs underwent both conventional culture as well as PCR for GBS detection. Cultured GBS isolates were serotyped by latex agglutination, those that were negative or had a weak positive reaction and those that were PCR positive but culture negative were additionally tested using multiplex PCR based on the detection of GBS capsular polysaccharide genes. Results The GBS carriage rate was 12.0% (95% CI: 9.4-15.0), with 8.6% positive by both culture and PCR and an additional 3.5% positive by PCR alone. Serotypes, Ia, Ib, II, III, IV, V, VI and VII were identified, with II the predominant serotype. All GBS isolates were susceptible to penicillin, ceftriaxone and vancomycin and 43/47 (91.5%) were susceptible to erythromycin and clindamycin. Conclusions GBS carriage is not uncommon in pregnant women living on the Thai-Myanmar border with a large range of serotypes represented.

Abstract Background Unprovoked superficial thrombophlebitis and subsequent venous thromboembolism are well-described albeit rare presenting features of advanced visceral malignancy that often manifest too late for curative intervention to be beneficial. Case Presentation We present the first reported case of early gastric carcinoma presenting with these paraneoplastic phenomena in an otherwise healthy farmer. The early presentation allowed for a curative partial gastrectomy, which itself was complicated by the presence of a deep vein thrombosis extending into the inferior vena cava. Fortunately, stabilization of the clot allowed for surgery to proceed without the need for a caval filter. The patient was referred for adjuvant chemotherapy and has since made an excellent recovery. Conclusions This case provides new evidence for the presentation of superficial thrombophlebitis in early gastric carcinoma and the potential for curative surgery in such instances. A high index of suspicion and a prompt diagnostic workup are essential for timely planning and execution of surgery in these early albeit rare presentations.