Enteric fever: Diagnostic value of clinical features.

Objectives: to evaluate the diagnostic value of clinical symptoms and signs in enteric fever and to propose a clinical diagnostic criterion. Design: Prospective observational study Setting: Kathmandu Medical College, Teaching Hospital, Kathmandu, Nepal Materials and methods: febrile patients with clinical diagnosis of enteric fever were included in the study with the aim of confirming diagnosis with blood culture, or bone marrow culture and evaluating the diagnostic accuracy of various clinical signs and symptoms. Results: 64% of the clinically diagnosed cases had blood/ bone marrow culture positive. The diagnostic accuracy of the various symptoms and signs excluding fever was between 42%-75.5%. Majority of the symptom and sign did not have very high diagnostic accuracy. Hence a diagnostic criterion was proposed and clinical features with diagnostic accuracy more than 50% were taken into consideration. Major criteria included fever with diagnostic accuracy of 64%, headache with accuracy of 75.5% and relative bradycardia with an accuracy of 66%. Minor criteria included vomiting, diarrhoea, Splenomegaly, chills and abdominal pain /discomfort with diagnostic accuracy of 57%, 55%, 55%, 53% and 51% respectively. Finally after combination of various major and minor criteria a final diagnostic criterion was proposed having an accuracy of 66% and including both major and minor clinical symptom and sign. Conclusion: clinical diagnosis of enteric fever will be very helpful in a country like ours. Though none of the clinical symptoms and sign have very high diagnostic accuracy a diagnostic criteria may be helpful. Criteria including both major and minor signs and symptoms would be the most appropriate diagnostic tool as it includes the important abdominal symptoms and signs of enteric fever. Key words: enteric fever, clinical features, diagnostic criteria.     

Heterogeneities in Consumer Diet Quality and Health Outcomes of Consumers by Store Choice and Income

Obesity and other diet-related health conditions have received much attention in the public health literature over the past two decades. This study investigates the relationship between household food budget shares at different food outlets with diet quality and weight-related health outcomes in the United States. Our analysis used event-level food purchase data from the national household food acquisition and purchases survey (FoodAPS). We find that, after controlling for observables, food purchase location is significantly associated with diet quality and body mass index (BMI). Our findings indicate that larger food budget shares at convenience stores and restaurants are linked with poor diet quality based on the healthy eating index-2015 (HEI-2015) scores and higher BMI. We further explored potential heterogeneity on outcomes of interest across income groups. Results suggest heterogeneous effects may exist across income groups: low-income households, who spent a larger share of their food budget at convenience stores and fast-food restaurants are related to poor diet quality and more likely to be obese. Our findings will help improve understanding of the causes of diet-related health problems and may illuminate potential avenues of intervention to address obesity.     

Two year audit of perinatal mortality at Kathmandu Medical College Teaching Hospital.

Introduction: Perinatal mortality rate is a sensitive indicator of quality of care provided to women in pregnancy, at and after child birth and to the newborns in the first week of life. Regular perinatal audit would help in identifying all the factors that play a role in causing perinatal deaths and thus help in appropriate interventions to reduce avoidable perinatal deaths. Aims and objectives: This study was carried out to determine perinatal mortality rate (PMR) and the factors responsible for perinatal deaths at KMCTH in the two year period from November 2003 to October 2005 (Kartik 2060 B.S. to Ashoj 2062). Methodology: This is a prospective study of all the still births and early neonatal deaths in KMCTH during the two year period from November 2003 to October 2005. Details of each perinatal death were filled in the standard perinatal death audit forms of the Department of Pediatrics, KMCTH. Perinatal deaths were analyzed according to maternal characteristics like maternal age, parity, type of delivery and fetal characteristics like sex, birth weight and gestational age and classify neonatal deaths according to Wigglesworth's classification and comparison made with earlier similar study. Results: Out of the 1517 total births in the two year period, 22 were still births (SB) and 10 were early neonatal deaths (ENND). Out of the 22 SB, two were of < 1 kg in weight and out of 10 ENND, one was of <1 kg. Thus, perinatal mortality rate during the study period was 19.1 and extended perinatal mortality rate was 21.1 per 1000 births. The important causes of perinatal deaths were extreme prematurity, birth asphyxia, congenital anomalies and associated maternal factors like antepartum hemorrhage and most babies were of very low birth weight. According to Wigglesworth's classification, 43.8% of perinatal deaths were in Group I, 12.5% in Group II, 28.1% in Group III, 12.5% in Group IV and 12.5% in Group V. Discussion: The perinatal death audit done in KMCTH for 1 year period from September 2002 to August 2003 showed perinatal mortality rate of 30.7 and extended perinatal mortality rate of 47.9 per 1000 births. There has been a significant reduction in the perinatal mortality rate in the last 2 years at KMCTH. Main reasons for improvement in perinatal mortality rate were improvement in care of both the mothers and the newborns and the number of births have also increased significantly in the last 2 years without appropriate increase in perinatal deaths. Conclusion: Good and regular antenatal care, good care at the time of birth including appropriate and timely intervention and proper care of the sick neonates are important in reducing perinatal deaths. Prevention of preterm births, better care and monitoring during the intranatal period and intensive care of low birth weight babies would help in further reducing perinatal deaths. Key words: Perinatal mortality rate (PMR), still births, early neonatal death (ENND), Total perinatal death (PND).     

Melioidosis imported into Nepal

This is a report of the first recognized case of melioidosis in Nepal. Illness began 1 month after returning from Malaysia after a 1 y stay. The case highlights the importance of ascertaining the travel history in any patient with a suspected infectious disease in this age of global travel.     

Community-acquired acute renal failure

Acute renal failure usually occurs during hospitalization, but may also be present on admission to the hospital. To define the causes and outcomes of community-acquired acute renal failure, we undertook a prospective study of patients admitted to the hospital with acute elevations in serum creatinine concentrations. Over a 17-month period, all admission serum creatinine determinations were screened for patients with values greater than 177 mumol/L (2 mg/dL). These values were compared with baseline creatinines to select patients with an acute elevation in serum creatinine occurring outside the hospital. One hundred patients were entered into the study, with an overall incidence of 1% of hospital admissions. Seventy percent of the patients had prerenal azotemia, 11% had intrinsic acute renal failure, 17% had obstruction, and 2% could not be classified. Mean peak serum creatinine (318 +/- 18 mumol/L [3.6 +/- 0.2 mg/dL]) and mortality (7%) was lowest in the group with prerenal azotemia. In this group, volume contraction due to vomiting, decreased fluid intake, diarrhea, fever, glucosuria, or diuretics was the most common underlying cause. The group with intrinsic acute renal failure had the most severe renal failure and the highest mortality (55%). Although ischemic acute tubular necrosis is the most common cause of hospital-acquired intrinsic acute renal failure, this etiology was seen in only one patient. Drug-induced nephrotoxicity and infection-related causes were the most common underlying etiologies of intrinsic acute renal failure. Obstructive renal failure had a mortality of 24% and was most commonly due to benign prostatic hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Peripheral Blood Grafts for T Cell–Replete Haploidentical Transplantation Increase the Incidence and Severity of Cytokine Release Syndrome

T cell–replete post-transplant cyclophosphamide (PTCy)-based protocols have led to increasing use of haploidentical allogeneic hematopoietic cell transplantation (haploHCT). With this approach, bidirectional alloreactivity causing nonengraftment or severe graft-versus-host disease (GVHD) is no a longer major barrier to haploHCT. PTCy eliminates alloreactive lymphocytes but spares CD34⁺ stem cells and regulatory T lymphocytes, resulting in reliable hematopoietic recovery with relatively low incidence of GVHD. The immediate post-haploHCT course, usually before PTCy administration, is often complicated by cytokine release syndrome (CRS). The predictors of CRS and its effect on outcomes post-transplant have not been fully ascertained. We analyzed the outcomes of 66 patients who received haploHCT at our institution. Using published CRS criteria we identified 48 patients who developed CRS. In multivariate analysis peripheral blood grafts were significantly associated with grade ≥ 2 CRS, compared with bone marrow. Grade ≥ 2 CRS (compared with grade < 2) was not associated with differences in overall survival or nonrelapse mortality. Severe CRS was associated with a statistically nonsignificant trend toward higher incidences of grades III to IV acute GVHD, especially in the context of peripheral blood grafts. CRS is a common complication after T cell–replete peripheral blood haploHCT, but post-transplant survival outcomes may not be affected in those with severe CRS.     

Pharmacokinetics of High-Dose Propylene Glycol–Free Melphalan in Multiple Myeloma Patients Undergoing Autologous Hematopoietic Cell Transplantation

High-dose melphalan followed by autologous stem cell transplant (ASCT) is standard of care for eligible patients with multiple myeloma (MM). Evomela (propylene glycol–free melphalan HCl [PG-Free Mel]; Spectrum Pharmaceuticals, Irvine, CA) was approved by the US Food and Drug Administration as conditioning therapy for ASCT in MM in 2 daily 100-mg/m² doses for a total dose of 200?mg/m². In this phase II, open-label study PG-Free Mel (Evomela) conditioning was given at single dose of 200?mg/m² on day ?2 pre-ASCT to establish pharmacokinetic (PK) parameters and safety. Twenty-four patients (median age, 64 years) were enrolled between August 2016 and February 2017. Myeloablation followed by successful neutrophil engraftment occurred at a median of 10 days in all patients. Peak melphalan concentration was observed at 10 minutes after infusion, whereas there was considerable variation in the maximum plasma concentration (C_max) and area under concentration time curve (AUC). Median C_max was 7380?ng/mL (interquartile range [IQR], 6522 to 8027). Similarly, median AUC was 533,552?ng/mL?min (IQR, 450,850 to 662,936). PG-Free Mel had an acceptable safety profile regardless of the exposure, with no mortality and an overall response rate of 96% and a very good partial response rate of 75%. In conclusion, although PG-Free Mel at a single dose of 200?mg/m² was safe, considerable PK variability was observed with the highest quartile having an ~3-fold higher AUC than the first quartile, suggesting that strategies for higher targeted exposure could be explored in future trials to optimize clinical benefit.     

N-acetylcysteine (NAC) diminishes the severity of PCB 126-induced fatty liver in male rodents

Potent aryl hydrocarbon receptor agonists like PCB 126 (3,3',4,4',5-pentachlorobiphenyl) cause oxidative stress and liver pathology, including fatty liver. Our question was whether dietary supplementation with N-acetylcysteine (NAC), an antioxidant, can prevent these adverse changes. Male Sprague-Dawley rats were fed a standard AIN-93G diet (sufficient in cysteine) or a modified diet supplemented with 1.0% NAC. After one week, rats on each diet were exposed to 0, 1, or 5μmol/kg body weight PCB 126 by i.p. injection (6 rats per group) and euthanized two weeks later. PCB-treatment caused a dose-dependent reduction in growth, feed consumption, relative thymus weight, total glutathione and glutathione disulfide (GSSG), while relative liver weight, glutathione transferase activity and hepatic lipid content were dose-dependently increased with PCB dose. Histologic examination of liver tissue showed PCB 126-induced hepatocellular steatosis with dose dependent increase in lipid deposition and distribution. Dietary NAC resulted in a reduction in hepatocellular lipid in both PCB groups. This effect was confirmed by gravimetric analysis of extracted lipids. Expression of CD36, a scavenger receptor involved in regulating hepatic fatty acid uptake, was reduced with high dose PCB treatment but unaltered in PCB-treated rats on NAC-supplemented diet. These results demonstrate that NAC has a protective effect against hepatic lipid accumulation in rats exposed to PCB 126. The mechanism of this protective effect appears to be independent of NAC as a source of cysteine/precursor of glutathione.