Efficacy of Ivermectin Treatment on Disease Progression Among Adults With Mild to Moderate COVID-19 and Comorbidities: The I-TECH Randomized Clinical Trial.

Importance: Ivermectin, an inexpensive and widely available antiparasitic drug, is prescribed to treat COVID-19. Evidence-based data to recommend either for or against the use of ivermectin are needed. Objective: To determine the efficacy of ivermectin in preventing progression to severe disease among high-risk patients with COVID-19. Design, Setting, and Participants: The Ivermectin Treatment Efficacy in COVID-19 High-Risk Patients (I-TECH) study was an open-label randomized clinical trial conducted at 20 public hospitals and a COVID-19 quarantine center in Malaysia between May 31 and October 25, 2021. Within the first week of patients' symptom onset, the study enrolled patients 50 years and older with laboratory-confirmed COVID-19, comorbidities, and mild to moderate disease. Interventions: Patients were randomized in a 1:1 ratio to receive either oral ivermectin, 0.4 mg/kg body weight daily for 5 days, plus standard of care (n = 241) or standard of care alone (n = 249). The standard of care consisted of symptomatic therapy and monitoring for signs of early deterioration based on clinical findings, laboratory test results, and chest imaging. Main Outcomes and Measures: The primary outcome was the proportion of patients who progressed to severe disease, defined as the hypoxic stage requiring supplemental oxygen to maintain pulse oximetry oxygen saturation of 95% or higher. Secondary outcomes of the trial included the rates of mechanical ventilation, intensive care unit admission, 28-day in-hospital mortality, and adverse events. Results: Among 490 patients included in the primary analysis (mean [SD] age, 62.5 [8.7] years; 267 women [54.5%]), 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease (relative risk [RR], 1.25; 95% CI, 0.87-1.80; P = .25). For all prespecified secondary outcomes, there were no significant differences between groups. Mechanical ventilation occurred in 4 (1.7%) vs 10 (4.0%) (RR, 0.41; 95% CI, 0.13-1.30; P = .17), intensive care unit admission in 6 (2.4%) vs 8 (3.2%) (RR, 0.78; 95% CI, 0.27-2.20; P = .79), and 28-day in-hospital death in 3 (1.2%) vs 10 (4.0%) (RR, 0.31; 95% CI, 0.09-1.11; P = .09). The most common adverse event reported was diarrhea (14 [5.8%] in the ivermectin group and 4 [1.6%] in the control group). Conclusions and Relevance: In this randomized clinical trial of high-risk patients with mild to moderate COVID-19, ivermectin treatment during early illness did not prevent progression to severe disease. The study findings do not support the use of ivermectin for patients with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04920942.

Efficacy of Early Treatment With Favipiravir on Disease Progression Among High-Risk Patients With Coronavirus Disease 2019 (COVID-19): A Randomized, Open-Label Clinical Trial.

BACKGROUND: The role of favipiravir in preventing disease progression in coronavirus disease 2019 (COVID-19) remains uncertain. We aimed to determine its effect in preventing disease progression from nonhypoxia to hypoxia among high-risk COVID-19 patients. METHODS: This was an open-label, randomized clinical trial conducted at 14 public hospitals across Malaysia (February-July 2021) among 500 symptomatic, RT-PCR-confirmed COVID-19 patients, aged ≥50 years with ≥1 comorbidity, and hospitalized within first 7 days of illness. Patients were randomized 1:1 to favipiravir plus standard care or standard care alone. Favipiravir was administered at 1800 mg 2×/day on day 1 followed by 800 mg 2×/day until day 5. The primary endpoint was rate of clinical progression from nonhypoxia to hypoxia. Secondary outcomes included rates of mechanical ventilation, intensive care unit (ICU) admission, and in-hospital mortality. RESULTS: Of 500 patients randomized (mean [SD] age, 62.5 [8.0] years; 258 women [51.6%]; 251 [50.2%] had COVID-19 pneumonia), 487 (97.4%) patients completed the trial. Clinical progression to hypoxia occurred in 46 (18.4%) patients on favipiravir plus standard care and 37 (14.8%) on standard care alone (OR, 1.30; 95% CI: .81-2.09; P = .28). All 3 prespecified secondary endpoints were similar between both groups. Mechanical ventilation occurred in 6 (2.4%) vs 5 (2.0%) (OR, 1.20; 95% CI: .36-4.23; P = .76), ICU admission in 13 (5.2%) vs 12 (4.8%) (OR, 1.09; 95% CI: .48-2.47; P = .84), and in-hospital mortality in 5 (2.0%) vs 0 (OR, 12.54; 95% CI: .76-207.84; P = .08) patients. CONCLUSIONS: Among COVID-19 patients at high risk of disease progression, early treatment with oral favipiravir did not prevent their disease progression from nonhypoxia to hypoxia. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov (NCT04818320).

Mapping the Scientific Landscape of Diabetes Research in Malaysia (2000-2018): A Systematic Scientometrics Study.

The escalated burden of diabetes on the population's health has catalyzed rigorous scientific research to produce appropriate evidence for treatment and control. Malaysia suffers from the leading diabetes epidemic within the Western Pacific region. It is crucial to map the scientific landscape of diabetes research for the country to identify trends in productivity and determine whether research efforts are directed toward the needs-gaps priority for evidence synthesis that could be used for the drafting of policies and guidelines. This systematic scientometrics study was conducted to map the scientific research output (trends and distribution, citation frequency, keywords link visualization, and thematic cluster conceptualization) related to diabetes between 2000-2018 in Malaysia. Using three international databases (PubMed, EMBASE, Scopus) and one local database (MyCite), scientific publication records related to diabetes in Malaysia between 2000 and 2018 were retrieved and analyzed using quantitative and qualitative methodologies. Microsoft Excel 2016, EndNote X9.2, BibExcel 2016, GraphPad Prism 8.0.1, VOS viewer software 1.6.13, and R software version 1.3.959 were used to analyze the trend and contents of diabetes publications. A total of 2094 publication records that accounted for 35,497 citations were analyzed. Kuala Lumpur was the most scientifically productive state in Malaysia, contributing 754 papers. Medical Journal of Malaysia had the highest number of publications. The inflection point of the Malaysian diabetes research output was in 2013, with most publications being non-collaborative research works. Most publications originated from academia, especially from local public universities. The overall publication productivity of diabetes research in Malaysia was conceptualized into eleven thematic clusters, with clinical and animal studies being the most prevalent themes. The diabetes literature in Malaysia has grown steadily over the past 19 years. However, the cumulative evidence remains inadequate and is insufficiently powered to guide policymaking and the control of diabetes. It does not yet seem feasible to direct the diabetes epidemic curve to a plateau for the Malaysian population based on Malaysian diabetes publications.

A Systematic Review of the Economic Burden of Type 2 Diabetes in Malaysia.

Diabetes causes significant disabilities, reduced quality of life and mortality that imposes huge economic burden on societies and governments worldwide. Malaysia suffers a high diabetes burden in Asia, but the magnitude of healthcare expenditures documented to aid national health policy decision-making is limited. This systematic review aimed to document the economic burden of diabetes in Malaysia, and identify the factors associated with cost burden and the methods used to evaluate costs. Studies conducted between 2000 and 2019 were retrieved using three international databases (PubMed, Scopus, EMBASE) and one local database (MyCite), as well as manual searches. Peer reviewed research articles in English and Malay on economic evaluations of adult type 2 diabetes conducted in Malaysia were included. The review was registered with PROSPERO (CRD42020151857), reported according to PRISMA and used a quality checklist adapted for cost of illness studies. Data were extracted using a data extraction sheet that included study characteristics, total costs, different costing methods and a scoring system to assess the quality of studies reviewed. The review identified twelve eligible studies that conducted cost evaluations of type 2 diabetes in Malaysia. Variation exists in the costs and methods used in these studies. For direct costs, four studies evaluated costs related to complications and drugs, and two studies were related to outpatient and inpatient costs each. Indirect and intangible costs were estimated in one study. Four studies estimated capital and recurrent costs. The estimated total annual cost of diabetes in Malaysia was approximately USD 600 million. Age, type of hospitals or health provider, length of inpatient stay and frequency of outpatient visits were significantly associated with costs. The most frequent epidemiological approach employed was prevalence-based (n = 10), while cost analysis was the most common costing approach used. The current review offers the first documented evidence on cost estimates of diabetes in Malaysia.

Clinical characteristics and risk factors for severe COVID-19 infections in Malaysia: A nationwide observational study.

BACKGROUND: COVID-19 emerged as a major public health outbreak in late 2019. Malaysia reported its first imported case on 25th January 2020, and adopted a policy of extensive contact tracing and hospitalising of all cases. We describe the clinical characteristics of COVID-19 cases nationwide and determine the risk factors associated with disease severity. METHOD: Clinical records of all RT-PCR confirmed COVID-19 cases aged ≥12 years admitted to 18 designated hospitals in Malaysia between 1st February and 30th May 2020 with complete outcomes were retrieved. Epidemiological history, co-morbidities, clinical features, investigations, management and complications were captured using REDCap database. Variables were compared between mild and severe diseases. Univariate and multivariate regression were used to identify determinants for disease severity. FINDINGS: The sample comprised of 5889 cases (median age 34 years, male 71.7%). Majority were mild (92%), and 3.3% required intensive care, with 80% admitted within the first five days. Older age (≥51 years), underlying chronic kidney disease and chronic pulmonary disease, fever, cough, diarrhoea, breathlessness, tachypnoea, abnormal chest radiographs and high serum CRP (≥5 mg/dL) on admission were significant determinants for severity (p<0.05). The case fatality rate was 1.2%, and the three commonest complications were liver injuries (6.7%), kidney injuries (4%), and acute respiratory distress syndrome (2.3%). INTERPRETATIONS: Lower case fatality rate was possibly contributed by young cases with mild diseases and early hospitalisation. Abnormal chest radiographic findings in elderly with tachypnoea require close monitoring in the first five days to detect early deterioration.

Challenges in the classification and management of Asian youth-onset diabetes mellitus- lessons learned from a single centre study.

It remains widely perceived that early-onset Type 2 Diabetes (T2D) in children and adolescents is rare and clinically distinct from Type 1 Diabetes (T1D). We studied the challenges of classifying subtypes of early-onset diabetes using clinical features and biomarkers, and management of these patients. We reviewed retrospectively the record of patients < 25 years old who attended the diabetes clinic in Penang General Hospital, Malaysia between 1st December 2012 and 30th June 2015. We examined their clinical features, C-peptide and pancreatic autoantibodies. Comparisons were made between T1D and T2D for magnitude, demographics, metabolic status and complications. We studied 176 patients with a mean age of 20 ± 3.7 years, 43.2% had T1D, 13.6% had T2D, and 13.6% had mixed features of both. When tested, pancreatic autoantibodies were positive in 59.4% of the T1D. T2D presented two years later than T1D at 14.3 years, 20% were asymptomatic at presentation, and 50% required insulin supplementation despite fasting c-peptide of > 250 pmol/L. HbA1C of ≤ 8.0% (64 mmol/mol) was achieved in 30.3% of T1D, 58.3% of T2D on OAD and 16.7% of T2D on insulin. The T2D had greater cardiovascular risk with higher body mass index, more dyslipidaemia, higher blood pressure and earlier onset of nephropathy. The overlapping clinical features, variable autoimmunity, and beta-cell loss complicate classification of young diabetes. Pancreatic autoantibodies and C-peptide did not always predict diabetes subtypes nor respond to insulin. The poor metabolic control and high cardiovascular risk burden among the T2D highlight the need for population-based study and focused intervention.

Estimating dengue incidence and hospitalization in Malaysia, 2001 to 2013.

BACKGROUND: Epidemiologic measures of the dengue burden such as prevalence and incidence are important for policy-making and monitoring the progress of disease control. It is a common practice where epidemiologic and economic research estimate dengue burden based on notification data. However, a basic challenge in estimating the incidence of dengue is that a significant proportion of infected population are asymptomatic. It can be overcome by using mathematical models that relate observed prevalence and mortality to incidence. In this study, we estimate the trend of dengue incidence and hospitalization in Malaysia. METHODS: This study is based entirely on the available secondary data sources on dengue in Malaysia. The age-specific incidence of dengue between 2001 and 2013 was estimated using the prevalence and mortality estimates in an incidence-prevalence-mortality (IPM) model. Data on dengue prevalence were extracted from six sero-surveys conducted in Malaysia between 2001 and 2013; while statistics on dengue notification and Case Fatality Rate were derived from National Dengue Surveillance System. Dengue hospitalization data for the years 2009 to 2013 were extracted from the Health Informatics Centre and the volumes of dengue hospitalization for hospitals with missing data were estimated with Poisson models. RESULTS: The dengue incidence in Malaysia varied from 69.9 to 93.4 per 1000 population (pkp) between 2001 and 2013.The temporal trend in incidence rate was decreasing since 2001. It has been reducing at an average rate of 2.57 pkp per year from 2001 to 2013 (p = 0.011). The age-specific incidence of dengue decreased steadily with dengue incidence reaching zero by age > 70 years. Dengue notification rate has remained stable since 2001 and the number of notified cases each year was only a small fraction of the incident cases (0.7 to 2.3%). Similarly, the dengue hospitalization was larger but still a small fraction of the incident cases (3.0 to 5.6%). CONCLUSION: Dengue incidence can be estimated with the use of sero-prevalence surveys and mortality data. This study highlights a reducing trend of dengue incidence in Malaysia and demonstrates the discrepancy between true dengue disease burden and cases reported by national surveillance system. Sero-prevalence studies with representative samples should be conducted regularly to allow better estimation of dengue burden in Malaysia.

Efficacy of Oral Mixed Tocotrienols in Diabetic Peripheral Neuropathy: A Randomized Clinical Trial.

Importance: Management of painful diabetic peripheral neuropathy remains challenging. Most therapies provide symptomatic relief with varying degrees of efficacy. Tocotrienols have modulatory effects on the neuropathy pathway and may reduce neuropathic symptoms with their antioxidative and anti-inflammatory activities. Objective: To evaluate the efficacy of oral mixed tocotrienols for patients with diabetic peripheral neuropathy. Design, Setting, and Participants: The Vitamin E in Neuroprotection Study (VENUS) was a parallel, double-blind, placebo-controlled trial that recruited participants from January 30, 2011, to December 7, 2014, with 12 months of follow-up. This trial screened 14 289 patients with diabetes from 6 health clinics and ambulatory care units from 5 public hospitals in Malaysia. A total of 391 patients who reported neuropathic symptoms were further assessed with Total Symptom Score (TSS) and Neuropathy Impairment Score (NIS). Patients 20 years or older with a TSS of 3 or higher and an NIS of 2 or higher were recruited. Interventions: Patients were randomized to receive 200 mg of mixed tocotrienols twice daily or matching placebo for 12 months. Patients with hyperhomocysteinemia (homocysteine level ≥2.03 mg/L) received oral folic acid, 5 mg once daily, and methylcobalamin, 500 µg thrice daily, in both groups. Main Outcomes and Measures: The primary outcome was patient-reported neuropathy TSS (lancinating pain, burning pain, paresthesia, and asleep numbness) changes at 12 months. The secondary outcomes were NIS and sensory nerve conduction test result. Results: Of 391 eligible patients, 300 were recruited (130 [43.3%] male; mean [SD] age, 57.6 [8.9] years; mean [SD] duration of diabetes, 11.4 [7.8] years) and 229 (76.3%) completed the trial. The TSS changes between the tocotrienols and placebo groups at 12 months (-0.30; 95% CI, -1.16 to 0.56; P = .49) were similar. No significant differences in NIS (0.60; 95% CI, -1.37 to 2.65; P = .53) and sensory nerve conduction test assessments were found between both groups. In post hoc subgroup analyses, tocotrienols reduced lancinating pain among patients with hemoglobin A1C levels greater than 8% (P = .03) and normohomocysteinemia (homocysteine level <2.03 mg/L; P = .008) at 1 year. Serious adverse events in both groups were similar, except more infections were observed in the tocotrienols group (6.7% vs 0.7%, P = .04). Results reported were of modified intention-to-treat analyses. Conclusions and Relevance: Supplementation of oral mixed tocotrienols, 400 mg/d for 1 year, did not improve overall neuropathic symptoms. The preliminary observations on lancinating pain among subsets of patients require further exploration. Trial Registration: National Medical Research Registry Identifier: NMRR-10-948-7327 and clinicaltrials.gov Identifier: NCT01973400.

Preserved glucagon-like peptide-1 responses to oral glucose, but reduced incretin effect, insulin secretion and sensitivity in young Asians with type 2 diabetes mellitus.

OBJECTIVE: Youth onset type 2 diabetes mellitus (YT2DM) is a globally rising phenomenon with substantial Asians representation. The understanding of its pathophysiology is derived largely from studies in the obese African-American and Caucasian populations, while studies on incretin effect are scarce. We examined the insulin resistance, ß-cell function (BC), glucagon-like peptide (GLP)-1 hormone and incretin effect in Asian YT2DM. RESEARCH DESIGN AND METHODS: This case-control study recruited 25 Asian YT2DM and 15 healthy controls, matched for gender, ethnicity and body mass index. Serum glucose, insulin, C peptide and GLP-1 were sampled during 2-hour oral glucose tolerance tests (OGTTs) and 1-hour intravenous glucose tolerance tests (IVGTTs). Insulin sensitivity was derived from the Quantitative Insulin Sensitivity Check Index (QUICKI), Oral Glucose Insulin Sensitivity Index (OGIS) in OGTT and surrogate index of SI from the minimal model (calculated SI, CSI). Acute insulin response (AIR) was obtained from IVGTT. Total BC was computed as incremental area under the curve of insulin/incremental area under the curve of glucose, during OGTT (BCOG) and IVGTT (BCIV), respectively. Disposition index (DI) was calculated using the product of insulin sensitivity and insulin secretion. GLP-1 response to oral glucose was calculated as incremental area under the curve of GLP-1 (ΔAUCGLP-1). Per cent incretin effect was estimated as 100×(BCOG-BCIV)/BCOG). RESULTS: The YT2DM had marked impairment in BC (>80% reduction in AIR and BCOG, p<0.001) and lower QUICKI (p<0.001), OGIS (p<0.001) and CSI (p=0.015) compared with controls. There was no difference in GLP-1 at all time points and ΔAUCGLP-1 but the per cent incretin effect was reduced in the YT2DM compared with controls (12.1±8.93 vs 70.0±4.03, p<0.001). CONCLUSIONS: Asian YT2DM showed similar GLP-1 response to oral glucose as controls but reduced incretin effect, BC and insulin sensitivity. The lack of compensatory mechanisms, as shown by the DI may be partly ascribed to the impaired incretin effect, similar to that of adult T2DM. TRIAL REGISTRATION NUMBER: NMRR-12-1042-13254.

Rural-urban comparisons of dengue seroprevalence in Malaysia.

BACKGROUND: Each year an estimated 390 million dengue infections occur worldwide. In Malaysia, dengue is a growing public health concern but estimate of its disease burden remains uncertain. We compared the urban-rural difference of dengue seroprevalence and determined age-specific dengue seroprevalence in Malaysia. METHODS: We undertook analysis on 11,821 subjects from six seroprevalence surveys conducted in Malaysia between 2001 and 2013, which composed of five urban and two rural series. RESULTS: Prevalence of dengue increased with age in both urban and rural locations in Malaysia, which exceeded 90 % among those aged 70 years or beyond. The age-specific rates of the 5 urban surveys overlapped without clear separation among them, while prevalence was lower in younger subjects in rural series than in urban series, the trend reversed in older subjects. There were no differences in the seroprevalence by gender, ethnicity or region. Poisson regression model confirmed the prevalence have not changed in urban areas since 2001 but in rural areas, there was a significant positive time trend such that by year 2008, rural prevalence was as high as in urban areas. CONCLUSION: Dengue seroprevalence has stabilized but persisted at a high level in urban areas since 2001, and is fast stabilizing in rural areas at the same high urban levels by 2008. The cumulative seroprevalence of dengue exceeds 90 % by the age of 70 years, which translates into 16.5 million people or 55 % of the total population in Malaysia, being infected by dengue by 2013.

A Two-Year Review on Epidemiology and Clinical Characteristics of Dengue Deaths in Malaysia, 2013-2014.

BACKGROUND: Dengue infection is the fastest spreading mosquito-borne viral disease, which affects people living in the tropical and subtropical countries. Malaysia had large dengue outbreaks in recent years. We aimed to study the demographics and clinical characteristics associated with dengue deaths in Malaysia. METHODS: We conducted a retrospective review on all dengue deaths that occurred nationwide between 1st January 2013 and 31st December 2014. Relevant data were extracted from mortality review reports and investigational forms. These cases were categorized into children (<15 years), adults (15-59 years) and elderly (≥60 years) to compare their clinical characteristics. RESULTS: A total of 322 dengue deaths were reviewed. Their mean age was 40.7±19.30 years, half were females and 72.5% were adults. The median durations of first medical contact, and hospitalization were 1 and 3 days, respectively. Diabetes and hypertension were common co-morbidities among adults and elderly. The most common warning signs reported were lethargy and vomiting, with lethargy (p = 0.038) being more common in children, while abdominal pain was observed more often in the adults (p = 0.040). But 22.4% did not have any warning signs. Only 34% were suspected of dengue illness at their initial presentation. More adults developed severe plasma leakage (p = 0.018). More than half (54%) suffered from multi-organ involvement, and 20.2% were free from any organ involvement. Dengue deaths occurred at the median of 3 days post-admission. Dengue shock syndrome (DSS) contributed to more than 70% of dengue deaths, followed by severe organ involvement (69%) and severe bleeding (29.7%). CONCLUSION: In Malaysia, dengue deaths occurred primarily in adult patients. DSS was the leading cause of death, regardless of age groups. The atypical presentation and dynamic progression of severe dengue in this cohort prompts early recognition and aggressive intervention to prevent deaths. TRIAL REGISTRATION: National Medical Research Registry (NMRR, NMRR-14-1374-23352).

A Review of Stroke Research in Malaysia from 2000 – 2014

Over 100 articles related to stroke were found in a search through a database dedicated to indexing all literature with original data involving the Malaysian population between years 2000 and 2014. Stroke is emerging as a major public health problem. The development of the National Stroke Registry in the year 2009 aims to coordinate and improve stroke care, as well as to generate more data on various aspects of stroke in the country. Studies on predictors of survival after strokes have shown potential to improve the overall management of stroke, both during acute event and long term care. Stroke units were shown to be effective locally in stroke outcomes and prevention of stroke-related complications. The limited data looking at direct cost of stroke management suggests that the health economic burden in stroke management may be even higher. Innovative rehabilitation programmes including braincomputer interface technology were studied with encouraging results. Studies in traditional complementary medicine for strokes such as acupuncture, Urut Melayu and herbal medicine were still limited.

Measles-Mumps-Rubella vaccine for children with egg allergy: Is admission for inpatient vaccination necessary?

Introduction: Children who develop any hypersensitivity reaction to eggs are routinely referred to hospital for Measles-Mumps-Rubella (MMR) vaccination as inpatients to prevent anaphylaxis. We aimed to study the association between hypersensitivity reactions after egg exposure and similar reactions after MMR immunisation; and examine the necessity of hospital admission for vaccination. Methods: A prospective observational study was conducted in Paediatric Department in Bukit Mertajam Hospital, Penang, between March and December 2014. Children referred from local polyclinics for inpatient MMR vaccination because of a history of egg allergy were recruited. The children were observed in the ward for post vaccination allergic reactions. Concurrently, a group of children without egg allergy was recruited from those admitted for other illnesses but had recent MMR vaccination at polyclinics. Parents of these children were interviewed and asked if they had observed any reactions post vaccination. In both groups, sociodemographics, medical history and family history of atopy were collected. Results: Eighty-seven subjects were recruited in this study. Fifty-four infants with egg allergy had previous mild allergic reactions after exposure to eggs or egg-related products. They were associated with a family history of egg hypersensitivity, personal history of acute gastroenteritis and upper respiratory tract infections. Two of them developed cutaneous rashes post vaccination during observation, but none developed anaphylactic or anaphylactoid reactions. Two infants among those without egg allergy had post vaccination fever. There was no association between egg allergy and hypersensitivity reactions to MMR vaccine (p=0.632). Conclusions: MMR vaccine can be safely administered to children with mild egg allergy, hence admission for vaccination in the hospital is not warranted. Risk stratification is required to ensure only infants with severe reactions will be admitted for vaccination.

Impact of Vitamin D Replacement on Markers of Glucose Metabolism and Cardio-Metabolic Risk in Women with Former Gestational Diabetes--A Double-Blind, Randomized Controlled Trial.

Gestational Diabetes Mellitus (GDM) and vitamin D deficiency are related to insulin resistance and impaired beta cell function, with heightened risk for future development of diabetes. We evaluated the impact of vitamin D supplementation on markers of glucose metabolism and cardio metabolic risk in Asian women with former GDM and hypovitaminosis D. In this double blind, randomized controlled trial, 26 participants were randomized to receive either daily 4000 IU vitamin D3 or placebo capsules. 75 g Oral Glucose Tolerance Test (OGTT) and biochemistry profiles were performed at baseline and 6 month visits. Mathematical models, using serial glucose, insulin and C peptide measurements from OGTT, were employed to calculate insulin sensitivity and beta cell function. Thirty three (76%) women with former GDM screened had vitamin D level of <50 nmol/L at baseline. Supplementation, when compared with placebo, resulted in increased vitamin D level (+51.1 nmol/L vs 0.2 nmol/L, p<0.001) and increased fasting insulin (+20% vs 18%, p = 0.034). The vitamin D group also demonstrated a 30% improvement in disposition index and an absolute 0.2% (2 mmol/mol) reduction in HbA1c. There was no clear change in insulin sensitivity or markers of cardio metabolic risk. This study highlighted high prevalence of vitamin D deficiency among Asian women with former GDM. Six months supplementation with 4000 IU of vitamin D3 safely restored the vitamin D level, improved basal pancreatic beta-cell function and ameliorated the metabolic state. There was no effect on markers of cardio metabolic risk. Further mechanistic studies exploring the role of vitamin D supplementation on glucose homeostasis among different ethnicities may be needed to better inform future recommendations for these women with former GDM at high risk of both hypovitaminosis D and future diabetes.

General practitioners' attitudes and preparedness towards Clinical Decision Support in e-Prescribing (CDS-eP) adoption in the West of Ireland: a cross sectional study.

BACKGROUND: Electronic clinical decision support (CDS) is increasingly establishing its role in evidence-based clinical practice. Considerable evidence supports its enhancement of efficiency in e-Prescribing, but some controversy remains. This study evaluated the practicality and identified the perceived benefits of, and barriers to, its future adoption in the West of Ireland. METHODS: This cross sectional study was carried out by means of a 27-part questionnaire sent to 262 registered general practitioners in Counties Galway, Mayo and Roscommon. The survey domains encompassed general information of individual's practice, current use of CDS and the practitioner's attitudes towards adoption of CDS-eP. Descriptive and inferential analyses were performed to analyse the data collected. RESULTS: The overall response rate was 37%. Nearly 92% of respondents employed electronic medical records in their practice. The majority acknowledged the value of electronic CDS in improving prescribing quality (71%) and reducing prescribing errors (84%). Despite a high degree of unfamiliarity (73%), the practitioners were open to the use of CDS-eP (94%) and willing to invest greater resources for its implementation (62%). Lack of a strategic implementation plan (78%) is the main perceived barrier to the incorporation of CDS-eP into clinical practice, followed by i) lack of financial incentives (70%), ii) lack of standardized product software (61%), iii) high sensitivity of drug-drug interaction or medication allergy markers (46%), iv) concern about overriding physicians' prescribing decisions(44%) and v) lack of convincing evidence on the systems' effectiveness (22%). CONCLUSIONS: Despite favourable attitudes towards the adoption of CDS-eP, multiple perceived barriers impede its incorporation into clinical practice. These merit further exploration, taking into consideration the structure of the Irish primary health care system, before CDS-eP can be recommended for routine clinical use in the West of Ireland.