An evaluation of continuous subcutaneous infusions across seven NHS acute hospitals: is there potential for 48-hour infusions?

BACKGROUND: Continuous subcutaneous infusions (CSCIs) are commonly used in the United Kingdom as a way of administering medication to patients requiring symptom control when the oral route is compromised. These infusions are typically administered over 24 h due to currently available safety data. The ability to deliver prescribed medication by CSCI over 48 h may have numerous benefits in both patient care and health service resource utilisation. This service evaluation aims to identify the frequency at which CSCI prescriptions are altered at NHS Acute Hospitals. METHODS: Pharmacists or members of palliative care teams at seven acute NHS hospitals recorded anonymised prescription data relating to the drug combination(s), doses, diluent and compatibility of CSCIs containing two or more drugs on a daily basis for a minimum of 2 days, to a maximum of 7 days. RESULTS: A total of 1301 prescriptions from 288 patients were recorded across the seven sites, yielding 584 discrete drug combinations. Of the 584 combinations, 91% (n = 533) included an opioid. The 10 most-common CSCI drug combinations represented 37% of the combinations recorded. Median duration of an unchanged CSCI prescription across all sites was 2 days. CONCLUSION: Data suggests medication delivered by CSCI over 48 h may be a viable option. Before a clinical feasibility study can be undertaken, a pharmacoeconomic assessment and robust chemical and microbiological stability data will be required, as will the assessment of the perceptions from clinical staff, patients and their families on the acceptability of such a change in practice.

Complications of percutaneous thoracostomy in neonates and infants.

OBJECTIVE: Percutaneous thoracostomy tubes are widely used in neonates, infants and children. The technique has a low complication rate. Lung perforation by a pigtail catheter is described in a single case report. STUDY DESIGN: This is a multi-center case series of neonates and infants who experienced thoracic organ injury following percutaneous chest tube placement between 2006 and 2015. RESULT: Eleven patients had chest tube-related thoracic organ injury. In six, tubes were placed during resuscitation. Gestational ages ranged from 24+6 weeks to term. Most of the chest tubes were pigtail catheters, and the most common injury was lung lobe perforation. Pericardium and mediastinum were also sites of injury. Some patients had small pleural effusions, with no other complications identified. CONCLUSION: Thoracic organ injury by percutaneous catheters may be more common than previously appreciated. Clinical and radiological findings are non-specific, and the diagnosis may not be apparent until autopsy.

First-trimester diagnosis of Meckel-Gruber syndrome by fetal ultrasound with molecular identification of CC2D2A mutations by next-generation sequencing.

We describe a first-trimester ultrasound examination in which the finding of fetal encephalocele and the cystic appearance of the kidneys raised suspicion of Meckel-Gruber syndrome (MKS). On the basis of sonographic findings, the patient elected termination of pregnancy, and post-termination studies using next-generation sequencing of a gene panel revealed two mutations (one previously described and the other novel) in the gene CC2D2A. Mutations in CC2D2A are known to cause MKS and Joubert syndrome, thus providing molecular confirmation of the clinical suspicion of MKS and opening the possibility for future prenatal diagnosis. This case highlights the ability to detect important anomalies in the first trimester using ultrasound, even in low-risk situations. It also demonstrates the growing role of new sequencing technologies in fetal testing.

Breast fine needle aspiration cytology: a review of current practice in Australasia.

AIMS: To investigate breast fine needle aspiration (FNA) cytology in Australasia, in terms of laboratory demographics, specimens received and quality control (QC). METHODS: A questionnaire was sent to all laboratories enrolled in the FNA module of the Royal College of Pathologists of Australasia Cytopathology Quality Assurance Program (QAP), requesting information about specimens received in a 3-month period in 2001 and in 2008. RESULTS: Responses were received from 81/180 laboratories in 2001 and from 94/200 in 2008. The mean number of cases per 3 months was 137 in 2001 and 141 in 2008 and for the 42 laboratories responding on both occasions, the mean number of cases declined from 191 to 149 (P=0.001). The mean percentage of malignant cases was 11.7% in 2001 and 10.5% in 2008 and the mean percentages of unsatisfactory rates were 21.7% and 25.2%, respectively; 43.2% of laboratories in 2001 and 40.4% in 2008 reported fewer than 50 cases for the 3-month period. The unsatisfactory rate was inversely proportional to the number of cases received. Most QC (69.1% in 2001, 71.3% in 2008) was carried out by correlation with any later histology. With no histology available, 35.8% of laboratories in 2001 and 48.9% in 2008 did no further follow-up. Follow-up of all diagnostic categories increased from 30.9% in 2001 to 44% in 2008. CONCLUSIONS: Breast FNA cytology is still actively undertaken in Australasia, but numbers have declined. Unsatisfactory rates have reached the Australian recommended upper limit and are inversely proportional to the total number of cases received. Overall QC measures are unchanged and consideration of a review of breast FNA guidelines is suggested.

Immunoglobulin isotypes and functional anti-FVIII antibodies in response to FVIII treatment in Balb/c and C57BL/6 haemophilia A mice.

Previous studies have demonstrated that genetic factors play an important role in determining the likelihood of formation of anti-factor VIII (FVIII) antibodies in haemophilia A patients. We were interested in characterizing the spectrum of FVIII antibody formation and the primary and secondary immune responses after FVIII administration in two different exon 16-disrupted haemophilia A mouse strains, Balb/c and C57BL/6. Balb/c and C57BL/6 E16 haemophilia A mice were used in all experiments. Total FVIII antibodies and FVIII inhibitors were measured using ELISA and Bethesda assays respectively. T- and B-cell cytokines were quantified using ELISA and flow cytometry. FVIII antibodies, but not functional inhibitors were detectable 1 week after the first FVIII treatment in both strains. These antibodies mainly belonged to the IgM and IgA isotypes. After the fourth FVIII treatment, neutralizing anti-FVIII antibodies were detected in both mouse strains: Balb/c (mean inhibitory titer 58 BU) and C57BL/6 (mean inhibitory titer 82 BU). IgG1 levels were similar in both strains but the IgG2A and IgG2B subclasses were higher in C57BL/6 mice. The results of intracellular cytokine staining of T cells indicated that the FVIII-treated C57BL/6 mice produced more IL10 and Th1 cytokines than the FVIII-treated Balb/c mice. These studies show that C57BL/6 mice develop a stronger immune response towards FVIII than Balb/c mice. We propose that the enhanced Th1 and IL10 cytokine micro-environment induced in C57BL/6 mice is responsible for this difference. Therefore, genetic strain-dependent differences must be considered when evaluating immunological outcomes in mouse models of haemophilia A.

The molecular mechanisms of immunomodulation and tolerance induction to factor VIII.

Successful factor (F) VIII replacement therapy in hemophilia A patients is confounded by the generation of inhibitory anti-FVIII antibodies (Ab) in 25-30% of treated patients. These antibodies, termed 'inhibitors', significantly increase morbidity within the hemophilia population and lower the quality of life for these patients. For the past 30 years, immune tolerance induction (ITI) has been the standard therapy to elicit immunological tolerance to FVIII in the clinic. ITI works well in approximately 75% of patients, but it is expensive, can take years to show effect and is in many cases practically challenging. Therefore, new immunological tolerance induction strategies are now being designed and tested in hemophilia A animal models. This review attempts to provide a comprehensive description, at both the cellular and molecular levels, of these novel advances in tolerance induction and immunomodulation of FVIII. We begin by briefly reviewing why and how the immune system generates a protective response against exogenous FVIII. This leads to a discussion of the latest advances in FVIII tolerance/immunomodulation technology. These advances include interesting methodologies to induce B cell specific tolerance in FVIII primed humans and animals, as well as newer T cell-specific therapies that modify and/or block co-stimulation. We also discuss methods to manipulate FVIII loading of antigen-presenting cells.

Blood transfusion for caesarean delivery complicated by placenta praevia.

AIM: This study was undertaken to determine if the need for red cell blood transfusion in placenta praevia could be predicted. METHODS: Data from a retrospective observational study of 246 obstetric patients, with placenta praevia, from 1999 to 2005 were analysed to generate a model to predict requirement for transfusion. RESULTS: Seventy-one patients were transfused. Independent risk factors for transfusion were gestational age at delivery of 32-35 weeks [odds ratio (OR): 2.6; 95% confidence interval (CI): 1.1-6.4] and caesarean combined with hysterectomy (OR: 29.4; 95% CI: 5.9-145.9; P < 0.001). No independent risk of transfusion was associated with maternal age, race, parity, smoking status, type of anaesthesia, caesarean combined with arterial balloon occlusion, grade of placenta, accreta and previous uterine surgery. CONCLUSIONS: Gestational age at delivery and type of surgery required are predictors of transfusion during caesarean for placenta praevia. Arterial balloon occlusion does not appear to increase transfusion risk and may be considered as one of the techniques in management.

Reduction of the immune response to factor VIII mediated through tolerogenic factor VIII presentation by immature dendritic cells.

BACKGROUND: The development of neutralizing antibodies to factor FVIII (FVIII) represents the most serious complication in the treatment of hemophilia A. OBJECTIVE: We have explored the potential of using immature dendritic cells (iDCs) to present FVIII in a tolerogenic manner to T cells. METHODS: The iDCs were isolated from hemophilic murine bone marrow and pulsed with canine cFVIII (cFVIII-iDCs) in the presence or absence of the NFkappaB pathway blocking compound Andrographolide (Andro-cFVIII-iDCs). Three weekly intravenous infusions of one million cFVIII pulsed-iDCs were administered to a group of five hemophilic Balb/c mice. Anti-FVIII antibody levels were monitored by functional Bethesda assay after four weekly intravenous challenges with 2 IU of cFVIII. RESULTS: We have shown that cFVIII in the presence or absence of Andro is efficiently taken up by iDCs and that this process does not result in the maturation of DCs or the activation of co-cultured T cells. Following repeated infusion of the cFVIII-iDCs and Andro-cFVIII-iDCs into hemophilic mice, which were subsequently challenged with cFVIII, long-term reductions of FVIII inhibitors of 25% and 40%, respectively, were documented. Studies of cytokine release and T-cell phenotypes indicate that the mechanisms responsible for reducing immunologic responsiveness to cFVIII appear to involve an expansion of Foxp3 T regulatory cells in the case of cFVIII-iDC infusion and the elaboration of the immunosuppressive cytokines IL-10 and TGF-beta following andrographolide-treated cFVIII-iDCs. CONCLUSIONS: This study shows that tolerogenic presentation of cFVIII to the immune system can significantly reduce immunogenicity of the protein.

Description and validation of a rapid (1 h) flow cytometry test for enumerating thermophilic bacteria in milk powders.

AIMS: The aim of this study was to develop a rapid assay for enumerating thermophilic bacteria in milk powder. METHODS AND RESULTS: The BactiFlow flow cytometer was used to count bacteria based on esterase activity in viable bacterial cells. A protocol for total viable bacteria was modified by heat-treating the sample to selectively label thermophilic bacteria. Samples of milk powder dissolved in 0.1% peptone were treated with 0.8% ethylenediaminetetraacetic acid to reduce background interference because of denatured milk proteins. Either thermophilic bacteria were added to the dissolved milk powder or milk powder solutions were incubated at 55 degrees C for 2-3 h to enrich the natural thermophile population for testing. Results from the BactiFlow were compared with traditional plate count results. CONCLUSIONS: Thermophilic bacteria in milk powder can be enumerated within 1 h using the BactiFlow flow cytometer. SIGNIFICANCE AND IMPACT OF THE STUDY: Microbiological test results obtained within 1 h can potentially be used to monitor manufacturing processes, effectively trace problems and provide confidence in the manufacture of product.

Black patients with chronic hepatitis C have a lower sustained viral response rate than non-Blacks with genotype 1, but the same with genotypes 2/3, and this is not explained by more frequent dose reductions of interferon and ribavirin*.

In previous hepatitis C virus (HCV) treatment studies, Black patients not only had a lower sustained viral response (SVR) rate to interferon and ribavirin (RBV) than non-Black patients but also a higher frequency of HCV genotype 1 (GT-1) infection. The aim of this community-based study was to determine whether Black patients have a lower SVR rate independent of genotype. We prospectively enrolled 785 patients (24.8% Black, 71.5% White, 3.7% others) who received interferon alpha-2b 3 MU three times weekly + RBV 1000-1200 mg/day for 24 weeks (GT-2/3) or 48 weeks (GT-1). Black patients were more commonly infected with GT-1 (86.8%vs 64.8%, P < 0.001) and less frequently had an SVR compared with non-Black patients (8.4%vs 21.6%, P < 0.001). Within GT-1, Black patients had a lower SVR rate than non-Black patients (6.1%vs 14.1%, P = 0.004) but not within GT-2/3 (50.0%vs 36.5%, P = 0.47). Black patients had lower baseline haemoglobin levels (14.8 vs 15.3 g/dL, P < 0.001) and neutrophil counts (2900 vs 4100/mm(3), P < 0.001) and required more frequent dose reductions of RBV (29.8%vs 18.5%, P < 0.001) and interferon (4.7%vs 1.6%, P = 0.012). However, dose reductions were not associated with lower SVR rates while early treatment discontinuations were (2.9%vs 25.7%, P < 0.001). Independent predictors of SVR were GT-1 [odds ratio (OR) 0.33; 95% confidence interval (CI) 0.20-0.55; P < 0.001], Black race (OR 0.45; 95% CI 0.22-0.93; P = 0.030), and advanced fibrosis, stages 3 + 4 (OR 0.53; 95% CI 0.31-0.92; P = 0.023). In conclusion, Black patients infected with HCV GT-1 (but not GT-2/3) have a lower SVR rate than non-Black patients. This is not explained by their lower baseline haemoglobin levels and neutrophil counts that lead to higher rates of ribavirin and interferon dose reductions.

Ninety patients with nonalcoholic steatohepatitis: insulin resistance, familial tendency, and severity of disease.

OBJECTIVE: Nonalcoholic steatohepatitis (NASH) is a common but poorly understood liver disease. Our aim was to study a large group of patients referred for Hepatology consultation to further characterize this disorder, in particular its demographics and range of severity. We also sought to better understand its etiology and its relationship to the insulin resistance syndrome, known as the metabolic syndrome or syndrome X. METHODS: Retrospective review of 90 patients seen over a 4-yr period. RESULTS: Ninety patients aged 14-70 with NASH seen at the Liver Clinics at either the University of Tennessee or the Medical University of South Carolina. Eleven had complications of portal hypertension and seven of these had undergone or were awaiting transplantation. NASH was seen in nine families either in siblings or in subsequent generations. Diabetes or insulin resistance were present in almost all in this cohort of patients with NASH. Diabetes, hyperlipidemia, hypertension, and atherosclerotic disease, the components of syndrome X, were common in this population. CONCLUSION: NASH affects males and females equally, and presents over a wide age range. Despite its usually benign course, 28% of patients had cirrhosis and almost half of those had complications of portal hypertension, necessitating liver transplantation. Obesity was common in affected patients and cirrhosis was more common in the morbidly obese. Familial clustering was common, with 18% of patients having a similarly affected first degree relative. The clinical features that define syndrome X (diabetes, hypertension, hyperlipidemia, and atherosclerotic disease) are common in affected patients. Studies of glucose tolerance demonstrated unsuspected diabetes in six, and insulin resistance (the hallmark of syndrome X) in 85% of those tested. We hypothesize that NASH is a disorder of genetic etiology and is the hepatic manifestation of syndrome X, the insulin resistance syndrome.

Genetic characterization of angiomatoid fibrous histiocytoma identifies fusion of the FUS and ATF-1 genes induced by a chromosomal translocation involving bands 12q13 and 16p11.

This case report documents the first karyotypic, fluorescence in situ hybridization, and genetic analysis of an angiomatoid fibrous histiocytoma that arose and recurred in the arm of a 5.5-year-old girl. Complex rearrangements between chromosomes 2, 12, 16, and 17 were noted, as well as deletion in the long arm of chromosome 11. Flow cytometry revealed a normal cell population. The t(12;16) site was further investigated using reverse transcriptase-polymerase chain reaction. We found that the FUS (also known as TLS) gene from 16p11 combined with the ATF-1 gene from 12q13 to generate a chimeric FUS/ATF-1. The FUS gene is rearranged in the t(12;16)(q13;p11) that characterizes myxoid liposarcoma and in acute myeloid leukemia with t(16;21)(p11;q22), while the ATF-1 gene is rearranged in the t(12;22)(q13;q12) found recurrently in clear cell sarcomas (malignant melanoma of soft parts). Thus, the FUS/ATF-1 gene in angiomatoid fibrous histiocytoma is predicted to code for a protein that is very similar to the chimeric EWS/ATF-1 found in clear cell sarcoma.

Paternal and maternal depressed mood during the transition to parenthood.

BACKGROUND: The course of postnatal depression was examined in first-time mothers and fathers with emphasis on the role of personality and parental relationships as risk factors. METHOD: 157 couples were assessed at four points: antenatally and at 6, 12 and 52 weeks postnatally. Various measures of mood and personality were administered at each of these assessment points. RESULTS: Examination of the factors associated with depressed mood suggested that a woman's relationship with her own mother was important in the early postpartum stage, and also her level of interpersonal sensitivity and neuroticism. For the father, his relationship with either his mother or father and his level of neuroticism were associated with his mood level early on. By the end of the first year couple morbidity increased, with rates of distress being at their highest for both parents, and factors associated with depressed mood being linked to partner relationship variables, at least for mothers. At most time points, antenatal mood and partner relationship were significant predictor variables for the postnatal mood of both mothers and fathers. LIMITATIONS: The sample had a relatively high level of education and this should be taken into account when considering the generalisation of findings to less educated populations. At the time of conducting this study, the Edinburgh Postnatal Depression Scale (EPDS) had only been validated for use in the first few months postpartum, and thus we used another scale to measure the mother's mood at the other assessment points (the Beck Depression Inventory). Current research would suggest that the EPDS is valid both antenatally and at other times in the first year postpartum. CONCLUSION: Whilst there was some consistency for mothers and fathers in the variables that predict their postpartum adjustment, these being antenatal mood and partner relationship, there is also evidence that adjustment to parenthood was related to different variables at different times. Early adjustment was related to the couple's relationship with their own parents, as well as their own personality. Later adjustment was related to the couple's functioning and relationship.

Novel natural products from soil DNA libraries in a streptomycete host.

As a route to accessing the potential chemical diversity of uncultivable microbes from the soil, combinatorial biosynthetic libraries were constructed by cloning large fragments of DNA isolated from soil into a Streptomyces lividans host. Four novel compounds, terragines A (1), B (2), C (3), and D (4), were isolated from recombinant 436-s4-5b1, and another novel compound, terragine E (5), was isolated from 446-s3-102g1. The structures were determined by a combination of spectroscopic techniques, primarily 2D NMR.

Absent pulmonary valve with tricuspid atresia or severe tricuspid stenosis: report of three cases and review of the literature.

Absence of the pulmonary valve occurs usually in association with tetralogy of Fallot and occasionally with an atrial septal defect or as an isolated lesion. Very rarely it occurs with tricuspid atresia, intact ventricular septum, and dysplasia of the right ventricular free wall and of the ventricular septum. We present the clinical, anatomic, and histologic findings of a new case, and for the first time, the data from two patients with absent pulmonary valve and severe tricuspid stenosis, who exhibited similar histologic findings. We also reviewed the clinical and anatomic data of 24 previously published cases and compared them with the new cases. In all three new cases, the myocardium of the right ventricle was very abnormal. In the two cases with tricuspid stenosis, large segments of myocardium were replaced with sinusoids and fibrous tissue. In the case with tricuspid atresia, the right ventricular free wall contained only fibroelastic tissue. The ventricular septum in all three patients showed asymmetric hypertrophy and in two of the three patients, multiple sinusoids had replaced large segments of myocardial cells. The left ventricular free wall myocardium and the walls of the great arteries were unremarkable. Our data indicate that myocardial depletion involving the right ventricular free wall and the ventricular septum and its replacement by sinusoids and fibroelastic tissue occur not only in cases of absent pulmonary valve with tricuspid atresia but also in cases of absent pulmonary valve with tricuspid stenosis. The degree of myocardial depletion varies and is more severe when the tricuspid valve is atretic.

Hepatitis C infection among survivors of childhood cancer.

Preliminary reports have suggested that survivors of childhood cancer and aplastic anemia who are infected with the hepatitis C virus (HCV) have a low risk for progression to significant liver disease. Among our surviving patients who were transfused between 1961 and March 1992, 77 (6.6% of surviving patients tested thus far) have evidence of HCV infection, whereas 4 surviving patients who were transfused after March 1992 are HCV-infected. One patient chronically infected with HCV died of liver failure, and 2 patients died of hepatocellular carcinoma. To characterize the risk for these and other complications, 65 patients are enrolled in a longitudinal study of HCV infection, of whom 58 (89.2%) had circulating HCV RNA at the time of protocol enrollment, with genotypes 1A and 1B most commonly isolated. Most enrolled patients have few or no symptoms, carry out normal activities, and have normal liver function. To date, 35 patients have undergone liver biopsy for abnormal liver function since the diagnosis of primary malignancy; central pathology review shows 28 (80%) have chronic active hepatitis, 25 (71%) have fibrosis, and 3 (9%) have cirrhosis. These preliminary data suggest that though most survivors of childhood cancer who are infected with HCV are clinically well, some are at risk for clinically significant liver disease. Identification of other HCV-infected patients and prospective monitoring of this cohort are ongoing to determine the risk for, and to identify factors associated with the progression of, liver disease.

Enhanced production of microbial metabolites in the presence of dimethyl sulfoxide.

Bacterial strains grown in the presence of low concentrations of dimethyl sulfoxide (DMSO) exhibit significant qualitative and quantitative alterations in the production of secondary metabolites. This effect was confirmed for a variety of biosynthetic families, including chloramphenicol (chorismate), thiostrepton (peptide) and tetracenomycin (polyketide), and for natural and recombinant strains of streptomycetes; a similar effect was seen with antibiotic-producing bacilli such as B. circulans. Increase in antibiotic production was not the result of a change in the growth rate of these organisms, since yields of biomass were similar in media with and without DMSO (up to 3%). We suggest that the addition of compounds such as DMSO provides a means of examining the full biosynthetic potential of microbes and might be used to promote secondary metabolite production. The mode of action of DMSO is not known, but in the cases studied it may act at the level of translation.

Suicide among young Australians, 1964-1993: an interstate comparison of metropolitan and rural trends.

OBJECTIVES: (i) To compare suicide rates in 15-24 year old men and women; and (ii) for 15-24 year old men, to investigate differences in suicide rates between metropolitan and rural area, and changes in method-specific suicide rates and, in particular, firearm and hanging suicide rates in rural and metropolitan areas. DESIGN: Retrospective analysis of Australian Bureau of Statistics (ABS) suicide data (1964-1993). SETTING: All Australian States. SUBJECTS: Young women and men aged 15-24 years who died by suicide. RESULTS: Male youth suicide rates rose substantially over the 30 years in all Australian States, whereas female rates did not increase. Increases in suicide rates in young men in small rural towns consistently exceeded those in metropolitan areas in all Australian States. Metropolitan rates in 1964 were higher than those in small rural towns, but by 1993 the position was reversed. Medium-sized cities were the only areas where there was no consistent interstate trend. Differences were noted in suicide base rates in different States. High car exhaust suicide rates were noted in Western Australia, and high firearm suicide rates in Tasmania and Queensland. The ratio of firearm suicide rates in small rural areas to those in metropolitan areas rose in all mainland States, but the same ratio for hanging suicide rates changed little. CONCLUSIONS: All Australian States reflect national suicide trend in relation to sex and residential area. In some States, particular suicide methods predominate. A decreasing trend in overall firearm suicide rates in young men in all States from 1984 to 1993 conceals substantial increases in firearm suicide rates in small rural areas in all mainland States over the 30-year period. This, together with the marked rate ratio difference in firearm suicides between metropolitan and small rural areas, suggests that particular risk factors for suicide are operating in small rural areas. The fact that hanging rate ratios changed little suggests that more general factors in male youth suicide are also operating in all areas. A better understanding of similarities and differences in health risks faced by metropolitan and rural youth is required.

Coroners' records of rural and non-rural cases of youth suicide in New South Wales.

OBJECTIVE: The aim of this study is to compare the frequency of certain putative risk factors for youth suicide in New South Wales (especially use of alcohol, social class, unemployment, and internal migration) in metropolitan and rural settings. METHOD: A review of 137 files for 10-19-year-old subjects judged by the Coroner to have committed suicide in 1988-1990 was carried out. RESULTS: One hundred and fifteen males and 21 females were identified (one subjects sex was unavailable). The male-female ratio was higher in rural (13.0) areas than non-rural (4.9 chi 2 = 12.14, p < 0.01). Of 27 subjects migrating within Australia, most migrated in a rural direction, and most to rural shires. Unemployment was somewhat more common among rural (38.5%) than non-rural (28.9%) subjects (chi 2 = 0.75, p = 0.39). Eleven of 50 non-rural parents of the deceased, but none of the 11 rural parents, were ranked as being in social classes 2 or 3. Alcohol consumption appeared more common in rural shires (44%) than metropolitan areas (32.9%), but this was not statistically significant. Medical services were less utilised prior to death in rural (15%) than non-rural (25%) areas (chi 2 = 1.69, p = 0.19), and a psychiatric diagnosis was recorded more commonly in non-rural areas. CONCLUSIONS: Incomplete coronial file data and relatively small numbers limit this study's conclusions. Male suicides, principally by firearms, predominated in rural areas. Youth firearm access remains highly relevant to rural communities. Possible trends among rural subjects toward rural migration, higher unemployment, lower social class and lower medical attendance may point to resource deprivation among this group; these matters require further investigation.

Serious hepatitis A: an analysis of patients hospitalized during an urban epidemic in the United States.

BACKGROUND: Memphis and Shelby County, Tennessee, experienced an epidemic of hepatitis A in 1994 and 1995. More than 1700 cases were reported. OBJECTIVE: To characterize the clinical features of patients hospitalized during a large urban epidemic of hepatitis A. DESIGN: Retrospective chart review. SETTING: 15 acute care hospitals in Shelby County, Tennessee. PATIENTS: 256 patients hospitalized with acute hepatitis A. MEASUREMENTS: Laboratory findings (such as prothrombin time and bilirubin level), complications, and mortality. RESULTS: The median patient age was 26 years. Thirty-nine complications occurred in 35 patients. Twenty patients (8%) had extrahepatic complications, and 5 (2%) died. Patients 40 years of age and older were more likely to have serious complications, including death (P = 0.014). Sixty-seven patients (26%) presented with coagulopathy (prothrombin time > or = 3 seconds prolonged). Fifty-four patients (21%) had a bilirubin level greater than 170 micromol/L (10 mg/dL). CONCLUSIONS: During this epidemic, hepatitis A caused serious illness and death. Complications were more frequent in patients 40 years of age and older, but young, healthy persons were also at risk for severe complications.