SummaryBackgroundWe aimed to investigate whether gatifloxacin, a new generation and affordable fluoroquinolone, is better than chloramphenicol for the treatment of uncomplicated enteric fever in children and adults.MethodsWe did an open-label randomised superiority trial at Patan Hospital, Kathmandu, Nepal, to investigate whether gatifloxacin is more effective than chloramphenicol for treating uncomplicated enteric fever. Children and adults clinically diagnosed with enteric fever received either gatifloxacin (10 mg/kg) once a day for 7 days, or chloramphenicol (75 mg/kg per day) in four divided doses for 14 days. Patients were randomly allocated treatment (1:1) in blocks of 50, without stratification. Allocations were placed in sealed envelopes opened by the study physician once a patient was enrolled into the trial. Masking was not possible because of the different formulations and ways of giving the two drugs. The primary outcome measure was treatment failure, which consisted of at least one of the following: persistent fever at day 10, need for rescue treatment, microbiological failure, relapse until day 31, and enteric-fever-related complications. The primary outcome was assessed in all patients randomly allocated treatment and reported separately for culture-positive patients and for all patients. Secondary outcome measures were fever clearance time, late relapse, and faecal carriage. The trial is registered on controlled-trials.com, number ISRCTN 53258327.Findings844 patients with a median age of 16 (IQR 9–22) years were enrolled in the trial and randomly allocated a treatment. 352 patients had blood-culture-confirmed enteric fever: 175 were treated with chloramphenicol and 177 with gatifloxacin. 14 patients had treatment failure in the chloramphenicol group, compared with 12 in the gatifloxacin group (hazard ratio [HR] of time to failure 0·86, 95% CI 0·40–1·86, p=0·70). The median time to fever clearance was 3·95 days (95% CI 3·68–4·68) in the chloramphenicol group and 3·90 days (3·58–4·27) in the gatifloxacin group (HR 1·06, 0·86–1·32, p=0·59). At 1 month only, three of 148 patients were stool-culture positive in the chloramphenicol group and none in the gatifloxacin group. At the end of 3 months only one person had a positive stool culture in the chloramphenicol group. There were no other positive stool cultures even at the end of 6 months. Late relapses were noted in three of 175 patients in the culture-confirmed chloramphenicol group and two of 177 in the gatifloxacin group. There were no culture-positive relapses after day 62. 99 patients (24%) experienced 168 adverse events in the chloramphenicol group and 59 (14%) experienced 73 events in the gatifloxacin group.InterpretationAlthough no more efficacious than chloramphenicol, gatifloxacin should be the preferred treatment for enteric fever in developing countries because of its shorter treatment duration and fewer adverse events.FundingWellcome Trust.

Background Diabetes, particularly type 1 diabetes, at younger ages can be a largely preventable cause of death with the correct health care and services. We aimed to evaluate diabetes mortality and trends at ages younger than 25 years globally using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. MethodsWe used estimates of GBD 2019 to calculate international diabetes mortality at ages younger than 25 years in 1990 and 2019. Data sources for causes of death were obtained from vital registration systems, verbal autopsies, and other surveillance systems for 1990-2019. We estimated death rates for each location using the GBD Cause of Death Ensemble model. We analysed the association of age-standardised death rates per 100 000 population with the Socio-demographic Index (SDI) and a measure of universal health coverage (UHC) and described the variability within SDI quintiles. We present estimates with their 95% uncertainty intervals. FindingsIn 2019, 16 300 (95% uncertainty interval 14 200 to 18 900) global deaths due to diabetes (type 1 and 2 combined) occurred in people younger than 25 years and 73•7% (68•3 to 77•4) were classified as due to type 1 diabetes. The age-standardised death rate was 0•50 (0•44 to 0•58) per 100 000 population, and 15 900 (97•5%) of these deaths occurred in low to high-middle SDI countries. The rate was 0•13 (0•12 to 0•14) per 100 000 population in the high SDI quintile, 0•60 (0•51 to 0•70) per 100 000 population in the low-middle SDI quintile, and 0•71 (0•60 to 0•86) per 100 000 population in the low SDI quintile. Within SDI quintiles, we observed large variability in rates across countries, in part explained by the extent of UHC (r²=0•62). From 1990 to 2019, age-standardised death rates decreased globally by 17•0% (-28•4 to -2•9) for all diabetes, and by 21•0% (-33•0 to -5•9) when considering only type 1 diabetes. However, the low SDI quintile had the lowest decline for both all diabetes (-13•6% [-28•4 to 3•4]) and for type 1 diabetes (-13•6% [-29•3 to 8•9]). Interpretation Decreasing diabetes mortality at ages younger than 25 years remains an important challenge, especially in low and low-middle SDI countries. Inadequate diagnosis and treatment of diabetes is likely to be major contributor to these early deaths, highlighting the urgent need to provide better access to insulin and basic diabetes education and care. This mortality metric, derived from readily available and frequently updated GBD data, can help to monitor preventable diabetes-related deaths over time globally, aligned with the UN's Sustainable Development Targets, and serve as an indicator of the adequacy of basic diabetes care for type 1 and type 2 diabetes across nations. Funding Bill & Melinda Gates Foundation.

The reported prevalence of systemic lupus erythematosus (SLE) in the general population is 20-150 cases per 100,000 population. The female to male ratio ranges from 7-15:1. An estrogen effect has been suggested by a number of observations for this difference. In children, sex hormonal effects are presumably minimal and, thus, the female to male ratio is 3:1. We report a series of three male patients who presented at the B. P. Koirala Institute of Health Sciences and were diagnosed to have lupus nephritis (LN). This is probably the first case series from Nepal on adult male LN. Male patients with SLE present mainly with renal involvement and seizures rather than photophobia and skin manifestations. The outcome also seems to be more serious in males. Thus, we believe that although male patients with lupus are not commonly seen, the manifestations are life threatening and early detection of the disease will lead to better outcome of these patients.

Introduction: Pesticide poisoning is a major health problem worldwide. In Nepal the most common cause is suicidal and pesticides account for more than fifty percent of cases. The objective of the study was to look in detail regarding the pesticide poisoning cases admitted at BPKIHS; their epidemiological profile, presentation, treatment and their outcome during the hospital stay. Drug therapy included specific antidotal drugs; atropine and pralidoxime (PAM) and some nonspecificdrugs: antimicrobials and sedatives. Methods: It was a retrospective study which included 2621 patients with poisoning of which 1661 cases were related to pesticides. Results: The mean age at presentation was 29 years. The mean duration of hospital stay was 6.7 days. The majority of patients 81.16% showed improvement whereas 6.6% of patients died within 24 hours of admission and 3.54% after 48 hours of admission. Among all the patients 0.5% patients were given ICU care and all others were managed in the different units of medicine ward. The total amount of atropine administered varied considerably from patient to patient, according to the need. Most of the cases were under the influence of alcohol. All the patients had a psychiatry evaluation before discharge. Conclusions: Pesticide poisoning is increasing in incidence and it is one of the preventable public health problems and includes mainly the patients’ age group 20-30 years. Due to easy availability of pesticides it is the most preferred method of suicide, the main reasons being impulsive act and increased indebtedness in the society.  Keywords: pesticides; organophosphorous poisoning.

Introduction: Co-morbid depression impacts negatively on quality of life in Chronic Kidney Diseasepatients. It is unclear if self-reported depression rating scales can be used accurately for screening.The aim of this study was to estimate prevalence of depression in patients on hemodialysis usingPatient Health Questionnaire-9 and compare Patient Health Questionnaire-9, Max Hamilton Ratingscale and International Classification of Disease-10 for diagnosis of depression. Methods: It was descriptive cross-sectional study conducted from November 2017 till June 2018.Ethical approval was taken from Ethical Review Board, Nepal Health Research Council. Informedand written consent was taken. Patients undergoing hemodialysis at Nepal Medical College for >3 months duration were included in study. Patients on hemodialysis were asked to fill validatedNepali translated version of Patient Health Questionnaire -9. Psychiatrist administered MaxHamilton Rating scale for diagnosis and categorization of depression and confirmed depressionbased on International Classification of Disease -10. Statistical Package for Social Sciences version 20was used for statistical analysis. Results: Total of 100 patients completed study. Median age was 47.5 years. Prevalence of depressionwas 78 (78%) using Patient Health Questionnaire-9 and 65 (65%) using Max Hamilton Rating scaleand 51 (51%) using International Classification of Disease -10. Mean depression in males using PatientHealth Questionnaire -9 was 7±4.33 and in females was 11.04±5.90. The most common symptom wasfatigue among 82 (82%). Conclusions: There is a high prevalence of depression in patients with Chronic Kidney Disease onhemodialysis compared to general population.