Behavioural Outcome in Children with Congenital Adrenal Hyperplasia: Experience of a Single Centre

The aim of this study was to determine the behavioral outcome in children with CAH and to identify the risk factors that may influence it. Participants (aged 6–18 years) included 29 girls and 20 boys with CAH and unaffected siblings (25 girls and 17 boys). Psychological adjustment was assessed with parent reports on the Child Behavior Checklist (CBCL). Information about disease characteristics was obtained from medical records. Our study reveals that there was higher incidence of parent-reported problem of anxious/depressed and withdrawn/depressed behaviours, somatic complaints, social, thought, and attention problems, and rule-breaking, aggressive, internalizing, and externalizing behaviour among children with CAH compared to controls. The prevalence of internalizing behaviour problems was higher in CAH boys compared with that of controls. Psychosocial adjustment of girls with CAH was found to be similar to unaffected female controls and was within the normal population range. Family income may be associated with behavioral outcome. Glucocorticoid dose may reflect disease severity which may be associated with behavioral outcome. We conclude that internalizing behavioral problem was prevalent among boys with CAH reflecting maladaptive adjustment in coping with chronic illness. This highlighted the importance of psychological and social support for the patients and their families

Out-patient intravaginal misoprostol versus in-patient intravaginal misoprostol for the treatment of first trimester incomplete miscarriage in UKMMC: a randomised controlled trial.

A prospective randomised controlled trial was conducted at a tertiary medical center on 154 patients for the treatment of spontaneous first trimester incomplete miscarriage. The intervention group (n=77) received out-patient administration of misoprostol whereas the control group (n=77) received in-patient administration of misoprostol. The intravaginal misoprostol dosage administered was 800mcg 8 hourly to maximum of 3 doses. They were reassessed at Day 7. The primary outcome evaluated were success of evacuation, side effects, cost and patient acceptability. The secondary outcomes evaluated were mean reduction of endometrial thickness, days of passing out POC, duration of bleeding and mean reduction in hemoglobin. Assessment for treatment failure was done at day 7. Surgical evacuation was then offered

Assessment of P-gp and MRP1 activities using MultiDrugQuant Assay Kit : a preliminary study of correlation between protein expressions and its functional activities in newly diagnosed acute leukaemia patients.

Multidrug resistance (MDR) is believed to be responsible for poor response of patients towards chemotherapy particularly patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). The best-characterized resistance mechanism is the one mediated by permeability-glycoprotein (P-gp) encoded by MDR1 gene, which is responsible for drug efflux. We studied P-gp and multidrug resistance-associated protein 1 (MRP1) expression and functional activities in 43 newly diagnosed acute leukemia cases (19 paediatric ALL cases and 24 adult AML cases). The expression and functional activities were examined using flow cytometry and MultiDrugQuant assay kit (involving calcein AM uptake and efflux). P-gp and MRP1 expression and its functional activities were observed in 68.4% of paediatric ALL. In adult AML cases, all cases expressed MRP1 and its functional activities but only 58.3% were positive for P-gp and its functional activities. We were able to show a significant correlation between the expression of the multidrug resistant protein (P-gp and MRP1) and their functional activity in adult AML and paediatric ALL samples

Validation of Self-Reported Smoker and Second Hand Smoke Exposure by Urinary Cotinine within The Malaysian Cohort Project

Background: Validation of self-reported questionnaire is very crucial in ensuring the quality and reliability of data collection. Objective: The aim of this study were i) to validate the questionnaire on tobacco smoke intake and second hand smoke exposure among The Malaysian Cohort (TMC) subjects through the determination of urinary cotinine levels, ii) to determine the optimal cut-off point of urine cotinine that discriminates smokers from non-smokers and iii) to estimate misclassification rate between self-reported smoking and urinary cotinine level.Methods: Urine samples from a total of 775 The Malaysian Cohort subjects (104 smokers, 102 former smokers and 569 non-smokers) were obtained and urinary cotinine levels were determined by high-performance liquid chromatography (HPLC). Differences between groups were compared using Kruskal Wallis and Mann-Whitney tests. The Receiver Operating Characteristic (ROC) curved was performed to define the optimal urinary cotinine cut-off point.Results: Urinary cotinine concentration significantly (p<0.001) correlated with smoking status (r=0.46), the average number of cigarettes smoked per day (r=0.53), duration of smoking (r=0.33) and number of cigarettes packed per year (r=0.47). Smokers and second hand smokers have significantly higher median cotinine levels (978.40 and 21.31 respectively) compared to non-smokers (15.52) and non-exposed (13.60) subjects. Cotinine level at cut-off value of 1.51 ng/mg creatinine is able to distinguish smokers and non-smokers with a sensitivity of 84.62% and specificity of 81.97%.Conclusion: The Malaysian Cohort self-reported smoking questionnaire is a reliable tool in assessing the use of tobacco and second hand smoke exposure among the subjects

Clinical features and risk factors for HIV encephalopathy in children

A prospective cohort study was conducted to determine the incidence of progressive encephalopathy (PE) and its associated clinical manifestations amongst a cohort of HIV infected children attending the HIV/AIDS clinic of the Pediatric Institute, Kuala Lumpur Hospital, Malaysia. Neurological and neurobehavioral assessments were performed in 55 children with HIV over a 24-month study period. Parameters assessed were physical and neurological assessments, CD4 counts, CD4 percentages, RNA viral loads and an IQ assessment at four monthly intervals. PE was diagnosed when patient developed at least one of the definitive criteria for PE based on the Consensus of Pediatric Neurology / Psychology Working Group, AIDS Clinical Trial 1996. The incidence of encephalopathy was 18.2% (n=10) in 2002. All the patients had hepatosplenomegaly, lymphadenopathy, abnormal deep tendon reflexes and five had impairment in brain growth. The CD4 counts and CD4 percentages were more likely to be associated with PE compared to the non-PE group

Preliminary study shows novel variant detected in the screening of RET gene in Malaysian patients with Hirschsprung’s disease

Hirschsprung’s disease (HSCR) is a disorder associated with congenital absence of ganglion cells in the gastrointestinal tract. Molecular analyses have identified variants in various genes including RET, GDNF, EDN3 and EDNRB that are involved in the development, migration and survival of neural cells. Variants in the receptor tyrosine kinase (RET) are most common and have been identified in 10-20% of sporadic HSCR patients. The objective of this study was to screen for RET gene variants in Malaysian patients with HSCR. Thirty-two patients with HSCR and 30 normal controls were recruited for this study. Mutations were screened using the Polymerase Chain Reaction – Denaturing High Performance Liquid Chromatography (PCR-dHPLC) approach. Mutations identified were then confirmed using Sanger sequencing. We identified one novel rare variant in exon 4 (A268A c807 G>C) in one patient. We also identified the common coding sequence variantsA45A (c135G>A), A432A (c1296A>G), L769L (c2307 T>G) and the G691S in our cohort of patients. In conclusion, our Malaysian patients with HSCR diseases showed the presence of similar RET gene common variants which have been described in other populations. We have also identified a novel variant in exon 4 (A268A)

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication