Physicochemical compatibility of caffeine citrate and caffeine base injections with parenteral medications used in neonatal intensive care settings.

PURPOSE: To investigate the physicochemical compatibility of caffeine citrate and caffeine base injections with 43 secondary intravenous (IV) drugs used in Neonatal Intensive Care Unit (NICU) settings. METHODS: Caffeine citrate (20 mg/mL or 10 mg/mL) or caffeine base injection (10 mg/mL) were mixed in a volume ratio of 1:1 with the secondary drug solution to simulate Y-site co-administration procedures in NICUs. Physical compatibility was evaluated based on visual observation for 2 h, against a black and white background and under polarised light, for changes in colour, precipitation, haze and evolution of gas. Chemical compatibility was determined from caffeine concentration measurements, using a validated high-performance liquid chromatography assay. RESULTS: Six of the 43 secondary drugs tested (aciclovir, amphotericin (liposomal), furosemide, hydrocortisone, ibuprofen and ibuprofen lysine) were physically incompatible with caffeine citrate undiluted injection (20 mg/mL), at their high-end, clinically relevant concentrations for NICU settings. However, when tested at lower concentrations, hydrocortisone (1 mg/mL) was physicochemically compatible, whereas furosemide (0.2 mg/mL) was physically incompatible with caffeine citrate. The six drugs which showed physical incompatibility with caffeine citrate 20 mg/mL injection were also physically incompatible with caffeine citrate 10 mg/mL solution. All 43 secondary drugs tested were physicochemically compatible with caffeine base injection. CONCLUSIONS: Most secondary test drugs, except aciclovir, amphotericin (liposomal), furosemide, hydrocortisone, ibuprofen and ibuprofen lysine, were physicochemically compatible with caffeine citrate injection. Caffeine base injection was physicochemically compatible with all 43 test drugs tested.

Prognostic gene expression signature for high-grade serous ovarian cancer.

BACKGROUND: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC. PATIENTS AND METHODS: Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies. RESULTS: Expression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02-2.71; P < 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to -), 5.4 (4.6-7.0), 3.8 (3.3-4.6), 3.2 (2.9-3.7) and 2.3 (2.1-2.6) years. CONCLUSION: The OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches.

Transcriptomic analysis of immunoglobulin novel antigen receptor (IgNAR) heavy chain constant domains of brownbanded bamboo shark (Chiloscyllium punctatum).

Cartilaginous fish are the evolutionarily oldest group of animals which possess antibodies, T cell receptors and major histocompatibility complex (MHC). The immunoglobulin novel antigen receptor (IgNAR) found in cartilaginous fish is a heavy chain homodimer which lacks light chain. The presence of non-canonical cysteine molecules and lack of CDR2 region make it more significant. To synthesize active binding domains based on variable region of IgNAR (VNAR), knowledge on the constant region dynamics play a significant role. The IgNAR exhibit species variations in its primary sequence features; hence, this study was conducted to determine the IgNAR heavy chain constant domain of the brownbanded bamboo shark (Chiloscyllium punctatum). Peripheral blood leukocytes (PBL) isolated from adult bamboo sharks were used to synthesize a cDNA library. A total of four billion residues of two million sequences (average length 218.41 bp) were obtained. Assembled sequences were aligned with published cartilaginous fish IgNAR constant region sequences. Transcriptome analysis revealed two distinct types of IgNAR in the brownbanded bamboo shark. Also, constant-1 domain sequences displayed 13 unique sequences which may reflect the least number of IgNAR gene clusters. The phylogenetic analysis revealed the closest relationship with the nurse shark (Ginglymostoma cirratum) followed by the wobbegong shark (Orectolobus maculatus) which belong to the same order Orectolobiformes. Analysis of the constant domains of the brownbanded bamboo shark IgNAR revealed an evolutionarily conserved nature and this knowledge can be used to design primers for VNAR cloning. Furthermore, knowledge on the structural features in IgNAR constant domains that increase the stability could be useful in the process of stabilizing human immunoglobulins.

How many doctors should we train for Sri Lanka? System dynamics modelling for training needs

Introduction: Over the years, Sri Lanka has achieved remarkable health gains for the money spent on health. Currently about 1450 doctors enter the health system annually. While some advocate opening up of new medical schools to address an apparent shortage of doctors in the country, others argue against it. Objective: To identify the number of doctors Sri Lanka need. Methodology: System dynamics, an analytical modelling approach and a methodology for studying complex feedback systems was used. Two sub models of "need" and "supply" were developed and simulated for a period of 15 years from 2017 to 2032 Results: At present the doctor to population ratio is 1:671 and 91% of the need has been met. This study shows that currently there is a shortage of doctors in the country. However, the supply will match the need by 2025/26. Increasing the number of doctors, will result in oversupply of doctors towards the latter part of the next decade. Conclusions: There is no acute necessity to open up new Medical Schools. However comprehensive health workforce analysis needs to be done once in 5 years and the number of doctors to be trained, decided accordingly.

Congenital generalized lipodystrophy: identification of novel variants and expansion of clinical spectrum.

Congenital generalized lipodystrophy (CGL) is an autosomal recessive disorder with two major subtypes. Variants in AGPAT2 result in CGL type 1 with milder manifestations, whereas BSCL2 variants cause CGL type 2 with more severe features. Muscle hypertrophy caused by lack of adipose tissue is present early in life in CGL patients. Our aim was to investigate 10 CGL patients from 7 different countries and report genotype-phenotype relationships. Genetic analysis identified disease-causing variants in AGPAT2 (five patients) and in BSCL2 (five patients), including three novel variants; c.134C>A (p.Ser45*), c.216C>G (p.Tyr72*) in AGPAT2 and c.458C>A (p.Ser153*) in BSCL2. We also report possible novel clinical features such as anemia, breast enlargement, steatorrhea, intraventricular hemorrhage and nephrolithiasis in CGL patients. Generalized lipodystrophy and muscular hypertrophy were the only features in all of our patients. Hepatomegaly was the second common feature. Some manifestations were exclusively noticed in our CGL2 patients; hypertrichosis, high-pitched voice and umbilical hernia. Bone cysts and history of seizures were noticed only in CGL1 patients. The findings of this study expand our knowledge of genotype-phenotype correlations in CGL patients. These results have important clinical applications in diagnosis and management of the CGL patients as well as in genetic counseling in families at-risk.

Motor function and behaviour across the ALS-FTD spectrum.

BACKGROUND: Behavioural/functional disturbances, characteristic of frontotemporal dementia (FTD), are also a feature of amyotrophic lateral sclerosis (ALS) and patients with combined ALS and FTD (FTD-ALS). AIM OF THE STUDY: To investigate the progression of behavioural disturbances in ALS and FTD using the FTD functional rating scale (FTDFRS). METHODS: Patients with ALS, FTD-ALS and FTD were recruited from specialist clinics. Baseline assessments included the FTDFRS and the ALS functional rating scale-revised (ALSFRS-R). Baseline assessments were included, as were longitudinal assessments in a proportion of patients. RESULTS: In total, 21 ALS, 12 FTD-ALS and 14 behavioural variant FTD (bvFTD) patients were included in the study. Moderate or severe behavioural disturbance was common in patients with ALS at baseline (47.6%), although less frequent than in bvFTD patients; patients with FTD-ALS displayed intermediate impairment. The ALSFRS-R showed the opposite pattern and did not correlate with the FTDFRS. During the follow-up period, significant (P < 0.05) behavioural deterioration was demonstrated in patients with bvFTD and FTD-ALS, with a trend for decline in patients with ALS (P = 0.06). CONCLUSION: Motor disturbance is the primary marker of disease severity in ALS, but behavioural and functional impairment are common, and may decline independently of motor function. As such, the FTDFRS may provide valuable information in the assessment and monitoring of ALS.

Appropriate use of echocardiography in an Australian regional centre.

BACKGROUND: The 2011 Appropriate Use Criteria (AUC) were developed by the American Society of Echocardiography (ASE) to provide guidance for referring physicians in response to growing concerns about unnecessary transthoracic echocardiogram (TTE) requests. When applied in multiple centres overseas, the rate of inappropriate referrals was as high as 22%. AIM: To assess the applicability of, and the level of adherence to the 2011 AUC in an Australian regional hospital where the AUC have not been tested systematically. METHODS: A retrospective analysis of 1000 inpatient and outpatient TTE referrals was conducted between January 2014 and June 2014 at Bendigo Hospital, a major regional referral hospital. RESULTS: Ninety-eight percent of the TTE referrals were classifiable. The most common indication for ordering TTE was to evaluate symptoms potentially related to a cardiac aetiology. Of the classifiable referrals, 77% were appropriate, 20.3% were inappropriate and 2.7% were uncertain. The most common inappropriate indications were routine surveillance of the left ventricular (LV) function in stable chronic cardiac conditions and routine perioperative evaluation of the LV function with no symptoms or signs of cardiovascular disease. Inappropriate referrals were significantly more frequent in outpatients compared with inpatients (24.4% vs 9.6%, P < 0.001). CONCLUSION: This study provides a novel insight into the ordering of TTEs in regional Australia. In this study, one in five referrals had an inappropriate indication and could be avoided. This may have significant implications for healthcare resources in regional centres, and strategies to reduce inappropriate echocardiography ordering need to be implemented.

Acute and long-term management of food allergy: systematic review.

BACKGROUND: Allergic reactions to food can have serious consequences. This systematic review summarizes evidence about the immediate management of reactions and longer-term approaches to minimize adverse impacts. METHODS: Seven bibliographic databases were searched from their inception to September 30, 2012, for systematic reviews, randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, controlled before-and-after and interrupted time series studies. Experts were consulted for additional studies. There was no language or geographic restrictions. Two reviewers critically appraised the studies using the appropriate tools. Data were not suitable for meta-analysis due to heterogeneity so were narratively synthesized. RESULTS: Eighty-four studies were included, but two-thirds were at high risk of potential bias. There was little evidence about acute management for non-life-threatening reactions. H1-antihistamines may be of benefit, but this evidence was in part derived from studies on those with cross-reactive birch pollen allergy. Regarding long-term management, avoiding the allergenic food or substituting an alternative was commonly recommended, but apart from for infants with cow's milk allergy, there was little high-quality research on this management approach. To reduce symptoms in children with cow's milk allergy, there was evidence to recommend alternatives such as extensively hydrolyzed formula. Supplements such as probiotics have not proved helpful, but allergen-specific immunotherapy may be disease modifying and therefore warrants further exploration. CONCLUSIONS: Food allergy can be debilitating and affects a significant number of people. However, the evidence base about acute and longer-term management is weak and needs to be strengthened as a matter of priority.

EAACI food allergy and anaphylaxis guidelines. Primary prevention of food allergy.

Food allergy can have significant effects on morbidity and quality of life and can be costly in terms of medical visits and treatments. There is therefore considerable interest in generating efficient approaches that may reduce the risk of developing food allergy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Prevention and is part of the EAACI Guidelines for Food Allergy and Anaphylaxis. It aims to provide evidence-based recommendations for primary prevention of food allergy. A wide range of antenatal, perinatal, neonatal, and childhood strategies were identified and their effectiveness assessed and synthesized in a systematic review. Based on this evidence, families can be provided with evidence-based advice about preventing food allergy, particularly for infants at high risk for development of allergic disease. The advice for all mothers includes a normal diet without restrictions during pregnancy and lactation. For all infants, exclusive breastfeeding is recommended for at least first 4-6 months of life. If breastfeeding is insufficient or not possible, infants at high-risk can be recommended a hypoallergenic formula with a documented preventive effect for the first 4 months. There is no need to avoid introducing complementary foods beyond 4 months, and currently, the evidence does not justify recommendations about either withholding or encouraging exposure to potentially allergenic foods after 4 months once weaning has commenced, irrespective of atopic heredity. There is no evidence to support the use of prebiotics or probiotics for food allergy prevention.

Primary prevention of food allergy in children and adults: systematic review.

BACKGROUND: Food allergies can have serious physical, social, and financial consequences. This systematic review examined ways to prevent the development of food allergy in children and adults. METHODS: Seven bibliographic databases were searched from their inception to September 30, 2012, for systematic reviews, randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, controlled before-and-after studies, interrupted time series studies, and prospective cohort studies. Experts were consulted for additional studies. There were no language or geographic restrictions. Two reviewers appraised the studies using appropriate tools. Data were not suitable for meta-analysis due to heterogeneity, so were narratively synthesized. RESULTS: Seventy-four studies were included, one-third of which were of high quality. There was no good evidence to recommend that pregnant or breastfeeding women should change their diet or take supplements to prevent allergies in infants at high or normal risk. There were mixed findings about the preventive benefits of breastfeeding for infants at high or normal risk, but there was evidence to recommend avoiding cow's milk and substituting with extensively or partially hydrolyzed whey or casein formulas for infants at high risk for the first 4 months. Soy milk and delaying the introduction of solid foods beyond 4 months did not have preventive benefits in those at high or normal risk. There was very little evidence about strategies for preventing food allergy in older children or adults. CONCLUSIONS: There is much to learn about preventing food allergy, and this is a priority given the high societal and healthcare costs involved.

EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy.

Food allergy can result in considerable morbidity, impact negatively on quality of life, and prove costly in terms of medical care. These guidelines have been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Guidelines for Food Allergy and Anaphylaxis Group, building on previous EAACI position papers on adverse reaction to foods and three recent systematic reviews on the epidemiology, diagnosis, and management of food allergy, and provide evidence-based recommendations for the diagnosis and management of food allergy. While the primary audience is allergists, this document is relevant for all other healthcare professionals, including primary care physicians, and pediatric and adult specialists, dieticians, pharmacists and paramedics. Our current understanding of the manifestations of food allergy, the role of diagnostic tests, and the effective management of patients of all ages with food allergy is presented. The acute management of non-life-threatening reactions is covered in these guidelines, but for guidance on the emergency management of anaphylaxis, readers are referred to the related EAACI Anaphylaxis Guidelines.

Association between child maltreatment and constipation: a school-based survey using Rome III criteria.

OBJECTIVE: Child abuse leads to multiple physical and psychosomatic sequelae. The aim of the present study was to evaluate the association between child abuse and constipation among schoolchildren. METHODS: Children 13 to 18 years of age were selected from 4 semiurban schools in Gampaha District, Sri Lanka. A self-administered questionnaire was used for data collection. Information regarding sociodemographic factors and gastrointestinal symptoms, child abuse, and somatisation were collected. Constipation was diagnosed using Rome III criteria. RESULTS: A total of 1792 children were included in the analysis (boys 975 [54.4%], mean age 14.4 years, standard deviation [SD] 1.3 years). One hundred thirty-eight (7.7%) fulfilled Rome III criteria for constipation. The number of children exposed to physical, emotional, and sexual abuse were, respectively, 438 (24.4%), 396 (22.1%), and 51 (2.8%). The prevalence of constipation was significantly higher in those exposed to sexual (5.8% vs 2.6% P = 0.03), emotional (40.9% vs 20.8%, P < 0.0001), and physical abuse (41.6% vs 23.2%, P < 0.0001). Mean somatisation score was higher in the total group of abused children with constipation (mean 18.6, SD 12.5) compared with those without (mean 13.9, SD 12.3; P = 0.027). Children with a history of abuse did not seek health care more often than children without this history. Patient-perceived severity of bowel symptoms was higher in children with physical abuse (23.7 vs 19.7 P = 0.001) and emotional abuse (25.4 vs 19.3 P < 0.0001). CONCLUSIONS: Childhood constipation shows a significant association with physical, sexual, and emotional abuse. Children with constipation complain of more somatic symptoms and bowel symptoms when they are exposed to abuse.

Evaluation of a programme in population health management for GP trainees.

OBJECTIVES: There is an increasing focus on improving outcomes for populations. General practice has a key role to play in achieving better patient outcomes. A programme in population health management was developed for GP trainees in their fourth year. The objective was to evaluate this educational intervention for impact upon learners, and lessons learned in the delivery of this innovative programme. METHODS: The evaluation approach combined qualitative and quantitative approaches involving GP trainees, GP trainers, and faculty. RESULTS: Involvement in the programme had a positive impact upon trainees' knowledge of population health management, developed transferable skills, and encouraged a shift in mindset to considering the needs of a practice population. The impact upon patients and practices is also described. Lessons learned for enhancing the programme are explained. CONCLUSIONS: Encouraging GP trainees to become involved with population health has significant benefits for their professional development. The Royal College of General Practitioners (RCGP) curriculum should consider incorporating population health competencies.

What influences stroke survivors with physical disabilities to be physically active? A qualitative study informed by the Theoretical Domains Framework.

BACKGROUND: Although the benefits of regular physical activity (PA) after stroke are well established, many stroke survivors do not achieve recommended PA levels. To date, studies exploring determinants to PA have not used a behaviour change theory and focused on stroke survivors with physical disabilities. As a precursor to an intervention development study, we aimed to use the Theoretical Domains Framework (TDF) to identify factors influencing PA in stroke survivors with physical disabilities in Singapore. METHODS: Between November 2021 and January 2022, we conducted interviews with 19 community-dwelling stroke survivors with a weak arm and/or leg. An interview guide based on the TDF was developed. We analysed the data deductively by coding interview transcripts into the theoretical domains of the TDF, and then inductively by generating themes and belief statements. To identify relevant TDF domains, we prioritised the domains based on the frequencies of the belief statements, presence of conflicting belief statements and evidence of strong belief statements. RESULTS: Eight of the 14 TDF domains were relevant, and included environmental context and resources, knowledge, social influences, emotion, reinforcement, behavioural regulation, skills and beliefs about capabilities. The lack of access, suitable equipment and skilled help often limited PA participation at public fitness spaces such as parks, gyms and swimming pools (environmental context and resources). While a few stroke survivors expressed that they had the skills to engage in regular PA, most expressed not knowing how much and how hard to work, which exercises to do, which equipment to use and how to adapt exercises and equipment (knowledge and skills). This often left them feeling afraid to try new activities or venture out to new places for fear of the unknown or adverse events (e.g., falls) (emotion). For some, doing the activities in a group encourage them to get out and engage in PA (social influences). CONCLUSIONS: In stroke survivors with physical disabilities, environmental context and resources had a significant influence on PA participation, and this often had a spill over effect into other domains. Our results inform a complex behaviour change intervention to improve PA after stroke, and has implications for intervention design for people with physical disabilities.

Development of a pharmaceutical science systematic review process using a semi-automated machine learning tool: Intravenous drug compatibility in the neonatal intensive care setting.

Our objective was to establish and test a machine learning-based screening process that would be applicable to systematic reviews in pharmaceutical sciences. We used the SPIDER (Sample, Phenomenon of Interest, Design, Evaluation, Research type) model, a broad search strategy, and a machine learning tool (Research Screener) to identify relevant references related to y-site compatibility of 95 intravenous drugs used in neonatal intensive care settings. Two independent reviewers conducted pilot studies, including manual screening and evaluation of Research Screener, and used the kappa-coefficient for inter-reviewer reliability. After initial deduplication of the search strategy results, 27 597 references were available for screening. Research Screener excluded 1735 references, including 451 duplicate titles and 1269 reports with no abstract/title, which were manually screened. The remainder (25 862) were subject to the machine learning screening process. All eligible articles for the systematic review were extracted from <10% of the references available for screening. Moderate inter-reviewer reliability was achieved, with kappa-coefficient ≥0.75. Overall, 324 references were subject to full-text reading and 118 were deemed relevant for the systematic review. Our study showed that a broad search strategy to optimize the literature captured for systematic reviews can be efficiently screened by the semi-automated machine learning tool, Research Screener.

The Physicochemical Compatibility of Sildenafil Injection with Parenteral Medications Used in Neonatal Intensive Care Settings.

Sildenafil is used to treat pulmonary hypertension in neonatal intensive care unit (NICU) settings. As multiple intravenous (IV) medications are co-administered in NICU settings, we sought to investigate the physicochemical compatibility of sildenafil with a range of IV drugs. Sildenafil 600 mcg/mL or 60 mcg/mL was mixed 1:1 with the secondary drug solution to simulate Y-site co-administration procedures. Physical compatibility was evaluated by visual observation against a black and white background and under polarized light for two hours for changes in colour, precipitation, haze and evolution of gas. Chemical compatibility was determined from sildenafil concentrations, using a validated, stability-indicating high-performance liquid chromatography assay. Sildenafil 600 mcg/mL was physicochemically compatible with 29 of the 45 drugs tested at 'high-end' clinical concentrations and physically incompatible with 16 drugs and six '2-in-1' parenteral nutrition solutions. Sildenafil 600 mcg/mL was compatible with lower, clinically relevant concentrations of calcium gluconate, heparin and hydrocortisone. Aciclovir, amoxicillin, ampicillin, ibuprofen lysine, indometacin, phenobarbitone and rifampicin were incompatible with sildenafil 600 mcg/mL, however these IV medications were compatible with sildenafil 60 mcg/mL. Sildenafil 600 mcg/mL and 60 mcg/mL were incompatible with amphotericin, flucloxacillin, furosemide, ibuprofen, meropenem and sodium bicarbonate. Sildenafil compatibility with commonly used syringe filters was also investigated. Sildenafil solution was compatible with nylon syringe filters, however, absorption/adsorption loss occurred with polyethersulfone and cellulose ester filters.

The epidemiology of anaphylaxis in Europe: a systematic review.

BACKGROUND: Anaphylaxis is an acute, potentially fatal, multi-organ system, allergic reaction caused by the release of chemical mediators from mast cells and basophils. Uncertainty exists around epidemiological measures of incidence and prevalence, risk factors, risk of recurrence, and death due to anaphylaxis. This systematic review aimed to (1) understand and describe the epidemiology of anaphylaxis and (2) describe how these characteristics vary by person, place, and time. METHODS: Using a highly sensitive search strategy, we identified systematic reviews of epidemiological studies, descriptive and analytical epidemiological investigations, and studies involving analysis of routine data. RESULTS: Our searches identified a total of 5,843 potentially eligible studies, of which 49 satisfied our inclusion criteria. Of these, three were suitable for pooled estimates of prevalence. The incidence rates for all-cause anaphylaxis ranged from 1.5 to 7.9 per 100,000 person-years. These data indicated that an estimated 0.3% (95% CI 0.1-0.5) of the population experience anaphylaxis at some point in their lives. Food, drugs, stinging insects, and latex were the most commonly identified triggers. CONCLUSIONS: Anaphylaxis is a common problem, affecting an estimated 1 in 300 of the European population at some time in their lives. Future research needs to focus on better understanding of the trends across Europe and identifying those most likely to experience fatal reactions.

The prevalence of diabetes and thyroid related autoantibodies in Sri Lankan children with type 1 diabetes and their unaffected siblings - The utility of a new screening assay.

Background: There is limited information about diabetes and thyroid related autoantibodies in children with type 1 diabetes (T1D) or their siblings in Sri Lanka. Objectives: To assess in T1D children and their unaffected siblings the prevalence of autoantibodies to (1) glutamic acid decarboxylase (GADA), insulinoma associated antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) using 3 Screen ICA™ (3-Screen) and individual ELISA assays; (2) insulin (IAA); and (3) thyroid peroxidase (TPOA), thyroglobulin (TgA) and the TSH receptor (TSHRA). Methods: We selected - (a) consecutive T1D children, and (b) their unaffected siblings of both sexes, from the T1D Registry at Lady Ridgeway Hospital, Colombo. Results: The median age (IQR) of 235 T1D children and 252 unaffected siblings was 11 (8.4, 13.2) and 9 (5.4, 14.9) years respectively, and the duration of T1D was 23 (7, 54) months. (1) T1D children (a) 79.1% were 3-Screen positive; (b) all 3-Screen positives were individual antibody positive (GADA in 74%; IA-2A 31.1%; ZnT8A 38.7%); (c) and were younger (p=0.01 vs 3-Screen negatives); (d) multiple autoantibodies were present in 45.1%; (e) IA-2A (p=0.002) and ZnT8A (p=0.006) prevalence decreased with T1D duration. (f) TPOA and TgA prevalence was higher in T1D children compared to unaffected siblings (28%, p=0.001 and 31%, p=0.004, respectively). (2) Unaffected siblings (a) 6.3% were 3-Screen positive (p=0.001 vs T1D), and 2.4% were positive for IAA; (b) four subjects had two diabetes related autoantibodies, one of whom developed dysglycaemia during follow-up. Conclusions: The 3-Screen assay, used for the first time in Sri Lankan T1D children and their siblings as a screening tool, shows a high prevalence of T1D related Abs with a high correlation with individual assays, and is also a helpful tool in screening unaffected siblings for future T1D risk. The higher prevalence of thyroid autoantibodies in T1D children is consistent with polyglandular autoimmunity.