Where do Children Die and what are the Causes? Under-5 Deaths in the Metro West Geographical Service Area of the Western Cape; South Africa; 2011

BACKGROUND:Accurate child mortality data are essential to plan health interventions to reduce child deaths.OBJECTIVES:To review the deaths of children aged etlt;5 years during 2011 in the Metro West geographical service area (GSA) of the Western Cape Province (WC); South Africa; from routine data sources.METHODSA retrospective study of under-5 deaths in the Metro West GSA was done using the WC Local Mortality Surveillance System (LMSS); the Child Healthcare Problem Identification Programme (Child PIP) and the Perinatal Problem Identification Programme (PPIP); and linking where possible.RESULTS:The LMSS reported 700 under-5 deaths; Child PIP 99 and PPIP 252; with an under-5 mortality rate of 18 deaths per 1 000 live births. The leading causes of death were pneumonia (25%); gastroenteritis (10%); prematurity (9%) and injuries (9%). There were 316 in-hospital deaths (45%) and 384 out-of-hospital deaths (55%). Among children aged etlt;1 year; there were significantly more pneumonia deaths out of hospital than in hospital (144 (49%) v. 16 (6%); petlt;0.001). Among children aged 1 - 4 years there were significantly more injury-related deaths out of hospital than in hospital (43 (47%) v. 4 (9%); petlt;0.001). In 56 (15%) of the cases of out-of-hospital death the child had visited a public healthcare facility within 1 week of death. Thirty-six (64%) of these children had died of pneumonia orgastroenteritis. CONCLUSIONS:Health interventions targeted at reducing under-5 deaths from pneumonia; gastroenteritis; prematurity and injuries need to be implemented across the service delivery platform in the Metro West GSA. It is important to consider all routine data sources in the evaluation of child mortality

Nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is a condition characterized by hepatomegaly, elevated serum aminotransferase levels, and a histologic picture similar to alcoholic hepatitis in the absence of alcohol abuse. Most patients with NASH are obese women, and many have diabetes mellitus, hypercholesterolemia, or hypertriglyceridemia. NASH has also been associated with a number of metabolic conditions, surgical procedures, and drug treatments. Most patients are asymptomatic. The most common sign of NASH is hepatomegaly. Stigmata of chronic liver disease are rare. Laboratory abnormalities include a 2-4-fold elevation of serum aminotransferase levels; other liver function test results are usually normal. Histologically, there is moderate to severe macrovesicular steatosis and lobular hepatitis with necrosis or ballooning degeneration and/or fibrosis. The pathogenesis of NASH is poorly understood, but lipid peroxidation and oxidative stress are the leading culprits. The natural history of NASH is unknown, but NASH seems to be a stable disease in most patients. Treatment of NASH is unproven, but weight reduction is recommended in obese patients. Small pilot studies of several drugs have shown promise, but large randomized clinical trials are awaited. Orthotopic liver transplantation is the treatment of choice for end-stage liver disease secondary to NASH.

The impact of interferon plus ribavirin on response to therapy in black patients with chronic hepatitis C. The International Hepatitis Interventional Therapy Group.

BACKGROUND & AIMS: Black patients with chronic hepatitis C have lower response rates than white patients to interferon monotherapy. The factors responsible for these differences are unknown, as is the impact of combination antiviral therapy on responsiveness among ethnic groups. We evaluated the impact of race on response to therapy in these patients. METHODS: A total of 1744 patients with chronic hepatitis C were randomized in 2 recent clinical trials to receive 24 or 48 weeks of interferon monotherapy or interferon-ribavirin combination therapy. RESULTS: Sustained virologic responses occurred in 27% of 1600 whites, 11% of 53 blacks (P = 0.01 vs. white), 44% of 32 Asians, and 16% of 27 Hispanics. No black patient had a sustained virologic response to interferon monotherapy, but 20% and 23% had sustained responses to 24 and 48 weeks, respectively, of combination therapy. Among black patients, 96% had hepatitis C genotype 1 compared with 65% of white subjects (P < 0.0001). Sustained response rates were similar for black and white patients with genotype 1 infection (23% vs. 22%, respectively). Compared with whites, black patients were older, weighed more, and had higher median Histologic Activity Index scores but did not differ in sex, baseline alanine aminotransferase or hepatitis C virus (HCV)-RNA levels, degree of fibrosis or percentage with cirrhosis, or other demographic variables. White subjects had a significantly greater reduction in HCV-RNA levels than blacks at weeks 4, 12, 24, and 48 of therapy, but only for black patients treated with interferon monotherapy. The decreased reduction of HCV-RNA reduction among blacks was eliminated by combination therapy. CONCLUSIONS: These observations suggest that the impaired responsiveness of black patients to interferon monotherapy can be overcome partially by combination interferon-ribavirin therapy.

The significance of hepatitis G virus in serum of patients with sporadic fulminant and subfulminant hepatitis of unknown etiology.

Excluding acute hepatic failure caused by drugs, the etiology of fulminant hepatitis (FH) remains unknown in many patients. There are conflicting data about a possible pathogenic role for the hepatitis G virus (HGV) in patients with cryptogenic fulminant hepatitis (non-A-E FH). We investigated the presence of circulating HGV in 36 patients with well-documented non-A-E fulminant and 5 patients with subfulminant hepatitis from 3 geographic locations in the United States. Serum HGV RNA was determined by reverse transcriptase-polymerase chain reaction using primers from the NS5 region of the HGV genome. HGV RNA was also measured before and after liver transplantation in 5 patients and at different time points in 7 patients. Serum samples were recoded and reanalyzed for HGV RNA using different primer sets to assess the validity of the HGV RNA assay. HGV was present in serum of 14 of the 36 patients (38.8%) with non-A-E fulminant hepatitis. Twenty percent of patients from the Northeast, 11% of the patients from the Southeast, and 50% from the Mid-Atlantic regions of the United States had circulating HGV RNA. The use of therapeutic blood products was significantly associated with the presence of serum HGV RNA (P <.02). Retesting for HGV RNA with different primers was positive in all but 1 case. HGV RNA is not causally related to non-A-E fulminant hepatitis. The finding of HGV RNA in serum from these patients is likely related to the administration of blood product transfusion after the onset of fulminant hepatitis.

Hepatitis C virus genotypes and viremia and hepatocellular carcinoma in the United States.

OBJECTIVE: Hepatitis C virus (HCV) is a well recognized cause of hepatocellular carcinoma (HCC). The pathogenic significance of HCV genotypes in hepatocarcinogenesis is undefined. The aim of this study was to investigate the genotypic distribution and viremic level of HCV in patients with HCV-associated cirrhosis with or without HCC. METHODS: A total of 28 HCV-infected patients with HCC (HCC+) and 38 patients with HCV-associated cirrhosis without HCC (HCC-) were studied. HCV genotype was assessed by the genotype-specific polymerase chain reaction (PCR) method of Okamoto and restriction fragment length polymorphism (RFLP) of the 5' untranslated region (5' UTR). Hepatitis C viremia was quantitated with the branched-chain DNA (bDNA) assay. RESULTS: Using the Okamoto method, we found genotype 1b in 64% of the HCC+ group and 74% of the HCC- group, 36% of the HCC+ group and 16% of the HCC- group were coinfected with a combination of genotype 1b and another genotype. Using the RFLP method, we found genotype 1b in 41% of the HCC+ group and in 24% of the HCC- group. Other genotypes accounted for 18% of the HCC+ group and 55% of the HCC- group; no combination genotypes were identified. Poor concordance occurred between the two genotyping methods. Mean bDNA levels were not significantly different between the two groups. CONCLUSIONS: Our study demonstrates that no particular HCV genotypes were associated with HCC and genotype did not appear to influence the development of HCV-associated HCC.

Transgenic expression of tpr-met oncogene leads to development of mammary hyperplasia and tumors.

Receptor tyrosine kinases are important in cell signal transduction and proliferation. Abnormal expression of tyrosine kinases often leads to malignant transformation. C-met is a tyrosine kinase receptor and its ligand is hepatocyte growth factor (HGF). HGF/c-met plays diverse role in regulation of cell growth, shape and movement. Constitutively activated met, such as tpr-met, is a potent oncogene in vitro, but its carcinogenic role in vivo remains unclear. Our study demonstrates that expression of tpr-met leads to development of mammary tumors and other malignancies in transgenic mice, and suggests that deregulated met expression may be involved in mammary carcinogenesis.

Association of hepatitis C virus and hepatocellular carcinoma in the United States.

Hepatocellular carcinoma (HCC) is a common cause of death from cancer on a worldwide basis. Chronic hepatitis B virus (HBV) infection is a well-documented pathogenic factor in the etiology of HCC, accounting for the majority of cases in certain geographic areas where HBV chronic-infection rates are high. Recent studies have implicated hepatitis C virus (HCV) infection as another major etiologic agent of hepatitis B surface antigen (HBsAg)-negative HCC. Studies in Europe have demonstrated that HCV infection is commonly associated with HCC; the prevalence rates of HCV ranged from 39% to 77% of HCC patients in these studies. In areas where HBV infection is endemic, such as Africa and Japan, the prevalence rates of anti-HCV in individuals with HCC have been reported at 29% and 68%, respectively. The significance of HCV and HBV infections in contributing to the occurrence of HBsAg-negative HCC has not been well established in the United States. The clinical consequences of infection with different genotypes of HCV (defined by nucleotide sequence divergence) are largely unknown: several studies have suggested differences among genotypes in terms of clinical expression, disease progression, and response to treatment with interferon. Our recent studies demonstrated that HCV and occult HBV infections account for the majority of cryptogenic HCC cases in the United States. Preliminary studies on the prevalence of HCV genotypes in patients with or without HCC but otherwise matched for hepatic histology did not reveal any association of specific genotype(s) with development of HCC.

Alcoholism treatment in Canada: a review of current programs and policy issues.

An overview of the specialized alcoholism treatment field in Canada is presented based on a 1976 national survey of 338 programs. Descriptive information on these programs is presented to provide an understanding of the state of current treatment efforts and to identify emersent policy issues in this field. Programs activities are described under six headings: (1) the pattern of program development, (2) types of treatment agencies, (3) treatment capacity and utilization, (4) the characteristics of persons using treatment services, (5) approaches employed in treatment, and (6) program costs and financing of alcoholism treatment. Findings from the national study are related to three policy issues: access, quality, and cost. The need for future research aimed at these issues is discussed.

Dental education and early careers of Canadian dentists: changes in attitudes, aspirations, and behavior.

Longitudinal data on two cohorts of Canadian dental students are examined in order to determine the nature of the changes in attitudes and aspirations which students experience during their undergraduate dental training and the extent to which attitudes and aspirations which students hold on graduation are consistent with subsequent attitudes and behavior in practice. Data are presented on three dimensions of career-related attitudes and behavior: (1) aspirations toward and actual involvement in alternative practice settings, (2) attitudes and behavior related to selected professional and community activities, and (3) attitudes toward specific issues in dentistry. The results indicate that the dental school has little influence on students for the dimensions considered and suggest that analysis of both student backgrounds and the early practice experience of dental graduates may be the key to understanding the career behavior of dental graduates.

The professional objectives of canadian dental students.

Data from a 1971 national study of Canadian dental education are used as a basis for examining the relative importance which dental students and faculty place on the professional objectives of economic gain and service. Students (N = 1,247) were asked to rank a set of career attributes in terms of their importance both for themselves and for other students. Dental school faculty (N = 510) were asked to assess whether students under emphasized or overemphasized a group of 16 parallel objectives. The results indicate substantial variations between the professional objectives of individual students, those ascribed to others by students, and the faculty's perception of student objectives.