Sujith J Chandy

Behaviour problems in children and adolescents with seizure disorder: associations and risk factors

PROBLEM Fifty million people worldwide have epilepsy of whom 33 million are children. Children and adolescents with epilepsy are known to have high rates of behaviour problems and psychiatric co-morbidity. No studies on this topic have been conducted in developing countries, although 90% of such children live in the developing world. METHODS The current study, set in Vellore in India, assessed the prevalence of psychopathology and its associations in children and adolescents with seizure disorder. One hundred and thirty two children were rated for psychopathology on the Child Behaviours Check List, and those who qualified as psychiatric cases were compared with those who did not. RESULTS Seizure disorder was associated with significant psychopathology in 53.8% children. Belonging to a higher income group and living in an urban area (OR: 7.61, 95% CI: 2.78-20.8, p=0.0001), having longer than 3 years of illness (OR: 2.39, 95% CI: 2.18-5.67, p=0.03) and being treated by more than one anti-epileptic drug (OR: 3.08, 95% CI: 1.09-8.72, p=0.03) independently predicted psychopathology. CONCLUSIONS Psychopathology reflected a complex interaction of seizures, socio-demographic factors and treatment related variables, in accord with studies in industrialised countries. Clinicians should be sensitive to identifying psychopathology since this may lead to effective interventions for this group of children.

Antimicrobial resistance surveillance among commensal Escherichia coli in rural and urban areas in Southern India.

Objective  To assess antimicrobial resistance (AMR) in Tamil Nadu, India.

A limited sampling strategy for tacrolimus in renal transplant patients

AIMS To develop and validate limited sampling strategy (LSS) equations to estimate area under the curve (AUC(0-12)) in renal transplant patients. METHODS Twenty-nine renal transplant patients (3-6 months post transplant) who were at steady state with respect to tacrolimus kinetics were included in this study. The blood samples starting with the predose (trough) and collected at fixed time points for 12 h were analysed by microparticle enzyme immunoassay. Linear regression analysis estimated the correlations of tacrolimus concentrations at different sampling time points with the total measured AUC(0-12). By applying multiple stepwise linear regression analysis, LSS equations with acceptable correlation coefficients (R(2)), bias and precision were identified. The predictive performance of these models was validated by the jackknife technique. RESULTS Three models were identified, all with R(2) > or = 0.907. Two point models included one with trough (C(0)) and 1.5 h postdose (C(1.5)), another with trough and 4 h postdose. Increasing the number of sampling time points to more than two increased R(2) marginally (0.951 to 0.990). After jackknife validation, the two sampling time point (trough and 1.5 h postdose) model accurately predicted AUC(0-12). Regression coefficient R(2) = 0.951, intraclass correlation = 0.976, bias [95% confidence interval (CI)] 0.53% (-2.63, 3.69) and precision (95% CI) 6.35% (4.36, 8.35). CONCLUSION The two-point LSS equation [AUC(0-12) = 19.16 + (6.75.C(0)) + (3.33.C1.5)] can be used as a predictable and accurate measure of AUC(0-12) in stable renal transplant patients prescribed prednisolone and mycophenolate.

Patterns of antibiotic use in the community and challenges of antibiotic surveillance in a lower-middle-income country setting: a repeated cross-sectional study in Vellore, South India.

OBJECTIVES There is considerable evidence linking antibiotic usage to bacterial resistance. Intervention strategies are needed to contain antibiotic use and thereby resistance. To plan appropriate strategies, it is imperative to undertake surveillance in the community to monitor antibiotic encounters and drivers of specific antibiotic misuse. Such surveillance is rarely in place in lower-middle-income countries (LMICs). This study describes antibiotic patterns and challenges faced while developing such surveillance systems in an LMIC. PATIENTS AND METHODS Surveillance of antibiotic encounters (prescriptions and dispensations) was carried out using a repeated cross-sectional design for 2 years in Vellore, south India. Every month, patients attending 30 health facilities (small hospitals, general practitioner clinics and pharmacy shops) were observed until 30 antibiotic encounters were attained in each. Antibiotic use was expressed as the percentage of encounters containing specific antibiotics and defined daily doses (DDDs)/100 patients. Bulk antibiotic sales data were also collected. RESULTS Over 2 years, a total of 52,788 patients were observed and 21,600 antibiotic encounters (40.9%) were accrued. Fluoroquinolones and penicillins were widely used. Rural hospitals used co-trimoxazole more often and urban private hospitals used cephalosporins more often; 41.1% of antibiotic prescriptions were for respiratory infections. The main challenges in surveillance included issues regarding sampling, data collection, denominator calculation and sustainability. CONCLUSIONS Patterns of antibiotic use varied across health facilities, suggesting that interventions should involve all types of health facilities. Although challenges were encountered, our study shows that it is possible to develop surveillance systems in LMICs and the data generated may be used to plan feasible interventions, assess impact and thereby contain resistance.

Antibiotic use and resistance: perceptions and ethical challenges among doctors, pharmacists and the public in Vellore, South India.

Inappropriate antibiotic use and resistance are major public health challenges. Interventional strategies require ascertaining the perceptions of major stakeholders and documenting the challenges to changing practice. Towards this aim, a qualitative study was conducted in Vellore, South India, using focus group discussions among doctors, pharmacists and public. There were eight groups with six to eight participants each. The themes explored were: understanding of infections, antibiotics and resistance; practices and pressure driving antibiotic use; and strategies for appropriate use. Data were transcribed, analysed, verified and a summary prepared with salient features and quotations. It was found that the public had minimal awareness of resistance, antibiotics and infections. They wanted symptomatic relief. Doctors reported prescribing antibiotics for perceived patient expectations and quick recovery. Business concerns contributed to antibiotics sales among pharmacists. Pharmaceutical industry incentives and healthcare provider competition were the main ethical challenges. Suggested interventional strategies by the participants included creating public awareness, better healthcare provider communication, improved diagnostic support, strict implementation of guidelines, continuing education, and strengthening of regulations. Perceived patient benefit, unrestricted autonomy and business-cum-industry pressures are promoting inappropriate use of antibiotics. Strategies improving responsible use will help preserve their effectiveness, and provide distributive justice and benefit for future generations.

Food marketing towards children: brand logo recognition, food-related behavior and BMI among 3-13-year-olds in a south Indian town.

Objectives To assess exposure to marketing of unhealthy food products and its relation to food related behavior and BMI in children aged 3–13, from different socioeconomic backgrounds in a south Indian town. Methods Child-parent pairs (n = 306) were recruited at pediatric clinics. Exposure to food marketing was assessed by a digital logo recognition test. Children matched 18 logos of unhealthy food (high in fat/sugar/salt) featured in promotion material from the food industry to pictures of corresponding products. Childrens nutritional knowledge, food preferences, purchase requests, eating behavior and socioeconomic characteristics were assessed by a digital game and parental questionnaires. Anthropometric measurements were recorded. Results Recognition rates for the brand logos ranged from 30% to 80%. Logo recognition ability increased with age (p<0.001) and socioeconomic level (p<0.001 comparing children in the highest and lowest of three socioeconomic groups). Adjusted for gender, age and socioeconomic group, logo recognition was associated with higher BMI (p = 0.022) and nutritional knowledge (p<0.001) but not to unhealthy food preferences or purchase requests. Conclusions Children from higher socioeconomic groups in the region had higher brand logo recognition ability and are possibly exposed to more food marketing. The study did not lend support to a link between exposure to marketing and poor eating behavior, distorted nutritional knowledge or increased purchase requests. The correlation between logo recognition and BMI warrants further investigation on food marketing towards children and its potential role in the increasing burden of non-communicable diseases in this part of India.

Impact of pediatric epilepsy on Indian families: Influence of psychopathology and seizure related variables

The impact of epilepsy on families has been little studied in the developing countries, where it is the most common neurological disorder among children. In Vellore, India, the impact on 132 families who had a child with epilepsy was rated with the Impact of Pediatric Epilepsy on the Family Scale (IPES). An adverse impact was experienced by 42% of families. Multivariate statistical analysis revealed four factors that were significantly associated with high impact: fewer years since diagnosis (OR=0.81, 95% CI=0.71-0.93), fewer months since last seizure (OR=0.58, 95% CI=0.39-0.87), treatment with multiple antiepileptic drugs (OR=4.34, 95% CI=1.22-15.52), and increased behavior problem scores on the Child Behavior Checklist (OR=1.10, 95% CI=1.05-1.14). Factor analysis of the IPES was also conducted as a comparison with earlier findings in a developed country. We suggest that early monotherapy should be employed whenever possible and that early recognition and treatment of associated psychological problems may help to reduce the burden on families.

A Reliable Limited Sampling Strategy for the Estimation of Mycophenolic Acid Area Under the Concentration Time Curve in Adult Renal Transplant Patients in the Stable Posttransplant Period

In renal transplant patients, there is an established relationship between mycophenolate area under the curve and clinical outcome. The authors have developed and validated a limited sampling strategy to estimate mycophenolic acid area under the curve to 12 hours (MPA AUC0-12) in a stable renal transplant Indian population prescribed a formulation of mycophenolate mofetil (Mofilet) along with prednisolone and tacrolimus. Intensive pharmacokinetic sampling was performed in 29 patients to measure mycophenolate concentration from trough to 12 hours postdose. Subsets of different timed concentrations against total measured 12-hour area under the curve were analyzed by linear regression. Three models were identified and linear regression analysis done. After all subset regression analysis, three, four, and five time point limited sampling strategies (LSS) were developed having correlation coefficients above 0.92. Validation of the models was performed using the jackknife method and their predictive performances were tested. After validation, the correlation coefficients for all three models were above 0.901. The five-point LSS had the best predictive performance with a bias (95% confidence interval) of 0.67% (-3.45 to 4.79) and mean precision 7.73%. In all patients except one, the five-point LSS estimation for total area under the curve was within ± 20% of the total measured AUC0-12. Trough concentration had a significant correlation with AUC0-12 (r2 = 0.69). However, if dosing in routine clinical practice was adjusted based only on trough concentration, 41% of our patients would require a different dose compared with monitoring using AUC0-12. The five-point LSS uses half-hourly samples from trough to 1.5 hour postdose with an additional sample at 3 hours. Ninety-three percent of our patients had a Cmax within 1.5 hour and inclusion of all the time points up to1.5 hour gave a better estimate of AUC0-12. This model simplifies area under the curve measurement with high precision in stable adult renal transplant patients.

High cost burden and health consequences of antibiotic resistance: the price to pay

INTRODUCTION Rising antibiotic resistance may negatively affect the health and cost of care for patients. This study aimed to determine the impact of antibiotic resistance on costs and health consequences for patients. METHODOLOGY A one-year observational study was conducted at Christian Medical College, Vellore, a tertiary care hospital, on patients admitted into medical wards with a preliminary diagnosis of suspected sepsis. Patients with confirmed bacteremia were analysed in two groups - resistant and susceptible - based on susceptibility of causative bacteria to the empiric antibiotics administered. Clinical data and details about costs incurred were collected from hospital records. Costs and health consequences were compared using Mann-Whitney U test and Fishers exact test. For median difference in costs, 95% bootstrap confidence interval was determined. RESULTS Overall, 220 patients were included. The median difference between resistant and susceptible groups in overall costs, antibiotic costs, and pharmacy costs was rupees (INR)/USD 41,993/700 (p = 0.001), 8,315/139 (p < 0.001) and 21,492/358 (p < 0.001), respectively. Health consequences such as intensive care admissions, complications, mortality, and length of stay were significantly higher in the resistant group as compared to susceptible group: 44% vs. 21% (p < 0.001), 56% vs. 37% (p = 0.006), 12% vs. 2% (p = 0.011), and 14 vs. 11 days (p = 0·027), respectively. CONCLUSIONS Antibiotic resistance has a significant impact on cost and health consequences. These findings provide a key message for policymakers and other stakeholders to initiate feasible strategies to tackle resistance and reduce the burden.

Using antibiotics responsibly: are we there yet?

Problems of antibiotic access and excess coexist in the world today and are compounded by rising rates of antibiotic resistance. We introduce two dimensions of responsibility to this context: responsible individual practices and a broad societal obligation centered on sustainability. Acting on these responsibilities requires recognizing the potential tensions between an individual optimum for antibiotic use and the societal optimum. We relate the tragedy of the commons metaphor to this situation to illustrate the complexity involved, and we draw on real-world experiences in Uganda, India, China and France. We conclude that we must form a global stewardship of antibiotics that can link access, innovation and conservation efforts across countries to ensure sustainable access to effective antibiotics for all who need them.