Influence of socio-economic status on Shiga toxin-producing Escherichia coli (STEC) infection incidence, risk factors and clinical features.

Shiga toxin-producing Escherichia coli (STEC) infection can cause serious illness including haemolytic uraemic syndrome. The role of socio-economic status (SES) in differential clinical presentation and exposure to potential risk factors amongst STEC cases has not previously been reported in England. We conducted an observational study using a dataset of all STEC cases identified in England, 2010-2015. Odds ratios for clinical characteristics of cases and foodborne, waterborne and environmental risk factors were estimated using logistic regression, stratified by SES, adjusting for baseline demographic factors. Incidence was higher in the highest SES group compared to the lowest (RR 1.54, 95% CI 1.19-2.00). Odds of Accident and Emergency attendance (OR 1.35, 95% CI 1.10-1.75) and hospitalisation (OR 1.71, 95% CI 1.36-2.15) because of illness were higher in the most disadvantaged compared to the least, suggesting potential lower ascertainment of milder cases or delayed care-seeking behaviour in disadvantaged groups. Advantaged individuals were significantly more likely to report salad/fruit/vegetable/herb consumption (OR 1.59, 95% CI 1.16-2.17), non-UK or UK travel (OR 1.76, 95% CI 1.40-2.27; OR 1.85, 95% CI 1.35-2.56) and environmental exposures (walking in a paddock, OR 1.82, 95% CI 1.22-2.70; soil contact, OR 1.52, 95% CI 2.13-1.09) suggesting other unmeasured risks, such as person-to-person transmission, could be more important in the most disadvantaged group.

Understanding pathways to social inequalities in childhood unintentional injuries: findings from the UK millennium cohort study.

BACKGROUND: Childhood unintentional injuries (UI) are common but continue to happen more often to children living in less advantaged socioeconomic circumstances (SEC). Our aim was to explore how early life factors mediate the association between SEC and UIs, using the UK Millennium Cohort Study. METHODS: We calculated risk ratios (RR) and 95% confidence intervals (95%CI) for parental report of UI occurring between age 3 and 5 years, using Poisson regression according to family income as a measure of SEC. We explored potentially mediating pathways by controlling associations between SEC and UI for groups of early life risks in three domains: factors that may influence environmental safety, supervision and the MCS child's abilities and behaviours. RESULTS: Twenty eight percent of children had a UI from 3 to 5 years old. Children from the lowest income quintile were more likely to be injured compared to those from the highest (RR 1.20 95%CI 1.05, 1.37). Sequentially controlling for early life factors that may influence environmental safety (RR 1.19 95%CI 1.02, 1.38), then supervision (RR 1.18, 95%CI 1.02, 1.36), and finally adding child's behaviour and abilities (RR 1.15, 95%CI 1.00, 1.34) into the model reduced the RR by 5, 10 and 25% respectively. CONCLUSIONS: Addressing factors that may influence environmental safety and supervision, and the child's abilities and behaviours only partly explains the increased UI risk between the highest and lowest income quintiles. Further research is required to explore factors mediating associations between SEC and specific mechanisms and types of injuries.

Do early-life exposures explain why more advantaged children get eczema? Findings from the U.K. Millennium Cohort Study.

BACKGROUND: Atopic dermatitis (eczema) in childhood is socially patterned, with higher incidence in more advantaged populations. However, it is unclear what factors explain the social differences. OBJECTIVES: To identify early-life risk factors for eczema, and to explore how early-life risk factors explain any differences in eczema. METHODS: We estimated odds ratios (ORs) for ever having had eczema by age 5 years in 14 499 children from the U.K. Millennium Cohort Study (MCS), with a focus on maternal, antenatal and early-life risk factors and socioeconomic circumstances (SECs). Risk factors were explored to assess whether they attenuated associations between SECs and eczema. RESULTS: Overall 35·1% of children had ever had eczema by age 5 years. Children of mothers with degree-level qualifications vs. no educational qualifications were more likely to have eczema (OR 1·52, 95% confidence interval 1·31-1·76), and there was a gradient across the socioeconomic spectrum. Maternal atopy, breastfeeding (1-6 weeks and ≥ 6 months), introduction of solids under 4 months or cow's milk under 9 months, antibiotic exposure in the first year of life and grime exposure were associated with an increased odds of having eczema. Female sex, Pakistani and Bangladeshi ethnicity, smoking during pregnancy, exposure to environmental tobacco smoke and having more siblings were associated with reduced odds for eczema. Controlling for maternal, antenatal and early-life characteristics (particularly maternal smoking during pregnancy, breastfeeding and number of siblings) reduced the OR for eczema to 1·26 (95% confidence interval 1·03-1·50) in the group with the highest educational qualifications compared with the least. CONCLUSIONS: In a representative U.K. child cohort, eczema was more common in more advantaged children. This was explained partially by early-life factors including not smoking during pregnancy, breastfeeding and having fewer siblings.

Deworming drugs for treating soil-transmitted intestinal worms in children: effects on growth and school performance.

BACKGROUND: In areas where intestinal worm infections occur, the World Health Organization recommends treating all school children at regular intervals with deworming drugs to improve growth and school performance. The evidence base for this policy needs to be established for countries to commit resources to implement these programmes. OBJECTIVES: To summarize the effects of deworming drugs used to treat soil-transmitted intestinal worms (nematode geohelminths) on growth and school performance in children. SEARCH STRATEGY: In May 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007, Issue 2), MEDLINE, EMBASE, LILACS, mRCT, and reference lists. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials (RCTs) comparing deworming drugs for geohelminth worms with placebo or no treatment in children aged 16 years or less, reporting on growth, nutritional status, school performance, or cognition tests. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the trials and evaluated methodological quality; one author extracted data, and another checked a sample. Continuous data were analysed using the weighted mean difference (WMD) with 95% confidence intervals (CI). The random-effects model (RE model) was used in the presence of statistically significant heterogeneity. MAIN RESULTS: Thirty-four RCTs, including six cluster-RCTs, met the inclusion criteria. Four trials had adequate allocation concealment, and three cluster-RCTs failed to take design effects into account in their analysis. Weight increased after one dose of a deworming drug (WMD 0.34 kg, 95% CI 0.05 to 0.64, RE model; 2448 children, 9 trials); however, there was considerable heterogeneity between trials that was not explained by background intestinal worm infection or intensity. A meta-analysis of multiple dose trials reporting on outcomes within a year of starting treatment showed no significant difference in weight gain (1714 children, 6 trials); however, one cluster-RCT did show effects on weight at one year in a subgroup analysis. In the seven multiple dose trials with follow up beyond 12 months, only one showed a significant increase in weight. Six of seven trials reported clear data on cognitive tests and school performance: five reported no significant effects, and one showed some improvements in three out of 10 cognitive tests. AUTHORS' CONCLUSIONS: Deworming drugs used in targeted community programmes may be effective in relation to weight gain in some circumstances but not in others. No effect on cognition or school performance has been demonstrated.

Exploration of cost effectiveness of active vaccination in the control of a school outbreak of hepatitis A in a deprived community in the United Kingdom.

In January 2006, an outbreak of hepatitis A occurred in a socio-economically deprived area of Liverpool, in the United Kingdom (UK), where extensive community outbreaks of hepatitis had previously occurred. A total of nine cases were confirmed. Five of these were linked within a primary school. The outbreak initially occurred among a close social contact group, but there was evidence of subsequent person-to-person transmission within a local primary school. The school was attended by 221 pupils (age range 4-12 years) with a total of 37 teaching and other staff (age range 22-71 years). Following local risk assessment, mass hepatitis A virus (HAV) vaccination was offered to all staff and pupils, as all were judged to be likely to have been in close contact with the affected pupils. A total of 188 of 217 eligible children (87%), and 33 of 37 staff (89%) were vaccinated. A salivary seroprevalence survey was conducted at the same time as vaccination to assess the benefit of this intervention in the school population. The survey confirmed high levels of susceptibility to hepatitis A in this setting (97.8%, 95% CI 91.6 to 99.62). The direct costs of intervention were estimated as euro5,000. The cost effectiveness of intervention varies widely (euro60.50 to euro2,099 per case avoided) depending on the expected attack rate, which is difficult to estimate due to heterogeneity in published studies.

Correlation of anti-emetic efficacy and plasma levels of ondansetron.

Intravenous ondansetron was administered at doses from 0.01 to 0.48 mg/kg every 4 h for three doses to patients receiving cisplatin 60-120 mg/m2 for the first time. Plasma samples were collected from 28 patients at baseline and at suitable times post-dose for pharmacokinetic analysis, and were assayed for ondansetron by high-pressure liquid chromatography. Plasma trough level was defined as the level before the third dose and 4 h area-under-the-curve (AUC4) was calculated with the linear trapezoidal method. Despite wide inter-patient variation, a correlation was seen between both trough level (r = 0.737, P less than 0.0001) and AUC4 (r = 0.903, P less than 0.001) related to dose. Trough level was also predictive of AUC4 (r = 0.824, P less than 0.0001). Frequency of complete protection (no emetic episodes) was equivalent throughout the AUC4 range, suggesting anti-emetic activity even at low AUC4. However, a trend toward better protection against failure (5 or more episodes) was seen when higher values of AUC4 were achieved, suggesting more consistent anti-emetic activity at moderate to high AUC4.

Light and electron microscopic features of tropical ulcer.

The histopathological features of 20 tropical ulcers with the electron microscopic findings on seven biopsy specimens are reported. The main findings were loss of epidermis associated with extensive dermal oedema, infiltration by polymorphonuclear leucocytes, and disruption of collagen bundles. The presence of micro-organisms at the site of tissue damage was shown and compared with the morphology of the organisms grown in culture. The most commonly identified bacteria were pleomorphic rods whose electron microscopic appearances accorded most closely with Fusobacteria grown in vitro. Spirochaetes, identified ultrastructurally as Treponema sp, were also present. There was no evidence of vasculitis to explain the rapid onset of ulceration, but necrotic changes seen in the dermis and the inflammatory cell infiltrate suggest that, associated with cell necrosis, bacteria previously shown in vitro have an important role in the pathogenesis of tropical ulcers.

Comparison of chemiluminescent DNA probe to cell culture for the screening of Chlamydia trachomatis in a gynecology clinic population.

Two hundred ninety-five endocervical swab specimens were obtained from patients presenting to a gynecology clinic in order to compare a nonradioactive chemiluminescent DNA probe with cell culture for detection of Chlamydia trachomatis. Discrepancies between cell culture and DNA probe were resolved by retesting and reculturing samples. In a population with a 10.8% prevalence, the corrected sensitivity, specificity, positive predictive value, and negative predictive value for the DNA probe were 80.6, 95.8, 71.4, and 97.3%, respectively. These results compare favorably to other non-culture methods such as direct fluorescent antibody and enzyme immunoassay tests for the detection of C trachomatis in populations with similar prevalence rates.

Tropical ulcer in Zambia.

The clinical features of 86 tropical ulcers in 64 subjects seen in hospitals and rural clinics in Zambia are described. Pre-ulcerative lesions were identified. 85% of the patients came from subsistence farming families. Few wore shoes but more than a quarter wore clothes below the knee at some time. No association with dental caries or gingivitis was observed. Ulcers were seen in some clinically well-nourished individuals of appropriate weight for height and occurred in areas where animal protein was plentiful. Family studies showed that concurrent cases within households were uncommon.

Anaerobic bacteria in tropical ulcer--the application of a new transport system for their isolation.

The successful isolation of anaerobes largely depends on adequate transportation of the specimens after collection. We are investigating the role of anaerobes in the pathogenesis of tropical ulcer and have used Hungate tubes with pre-reduced peptone yeast broth and agar as a transportation system. The medium included 0.05% cysteine and 0.03% sodium formaldehyde sulphoxylate as an Eh buffer. Resazurin 1 microgram/ml seved as an Eh indicator. We found the tubes convenient to use and very reliable at maintaining anaerobiasis.

An unusual cause of stroke in a young adult.

Cerebral vascular accidents of uncertain origin in any patient pose a burden on the family physician to uncover the underlying cause by means of a thorough and concise workup. Even though cardiac tumors are rare, missing the diagnosis may lead to devastating results. The case reported here is of a 40-year-old man with a left atrial myxoma as the cause of his embolic cerebral infarct.

Oxygen consumption in normally grown, small-for-dates and large-for-dates new-born infants.

1. Serial measurements of minimal oxygen consumption (V(O2)) have been obtained from nineteen healthy new-born infants in order to find out how body weight, gestational age and age after birth affected V(O2). The first measurement of V(O2) was done within 12 hr of birth, and further measurements were made at intervals until the baby left hospital.2. The majority of the infants (seventeen) weighed less than 2.5 kg at birth, and were ;premature' according to international definition. Gestational age, calculated from the mother's last menstrual period, was corroborated by clinical data and obstetrical history. The babies were divided into four groups according to birth weight and gestational age combined (see Table 1). Babies in the first two groups were the appropriate weight for dates (i.e. normally grown), babies in the other two groups were either small-for-dates or large-for-dates.3. At birth minimal V(O2) was closely correlated with birth weight in all babies and appeared to be directly proportional to it. The value for V(O2)/kg was similar in all groups. V(O2) was not related to gestational age per se. However, in the two normally grown groups V(O2) was roughly related to gestational age because birth weight was related to gestational age.4. In all babies minimal V(O2) rose progressively with increasing age after birth; a marked increase in V(O2) occured in the first week of life, despite a small decline in body weight.5. At a given age after birth differences in V(O2)/kg between the four groups were mostly less than 10%, and in general the differences were not statistically significant. Values for minimal V(O2) in all four groups were roughly:5 ml. O(2)/kg.min at < 12 hr of age.7 ml. O(2)/kg.min at 7-14 days of age.9 ml. O(3)/kg.min at about 2 months of age.6. It is concluded that:(a) At birth minimal V(O2) is largely determined by birth weight. V(O2)/kg is little affected by either rate of growth in utero or gestational age.(b) Minimal V(O2) is a function of age after birth as well as of body weight, and the value for V(O2)/kg increases as the baby gets older.

Schistosoma mansoni: activation of hemolytic activity in homogenates from live adult worms.

We have previously described hemolytic activity in extracts of lyophilized Schistosoma mansoni adult worms. In contrast, freshly homogenized live worms have little hemolytic activity. However, preincubation of the homogenate at 38 C, pH 5.1 for 22 hr resulted in an 18 fold increase in specific activity (Hb released/mg protein) due to dramatic increases in hemolytic activity and decreases in protein concentration. No activation occurred when the homogenate was boiled prior to preincubation or when preincubation was performed at 4 C. In addition, a thermostable inhibitor of hemolytic activity is present in freshly homogenized live adult S. mansoni. Hydrolysis of the inhibitor and activation of the hemolytic agent appear to be due in part to hydrolytic activity of one or more cysteinyl proteinases.

A retrospective study of tamoxifen and endometrial cancer in breast cancer patients.

OBJECTIVE: To assess the relationship between low-dose tamoxifen, usage and endometrial cancer in breast cancer patients. METHODS: In this case-control study, the records of the 1017 patients treated at Wilford Hall Medical Center for primary breast cancer between 1978 and 1989 were reviewed. Dose and duration of tamoxifen therapy were recorded as well as the presence of a uterus. Potential confounding variables including diabetes mellitus, hypertension, age, weight, tobacco use, and family history of breast or gynecologic cancer were recorded. RESULTS: Of the 1017 patients in the study, 56 had inadequate records and 375 had undergone a prior hysterectomy and these patients were excluded from the study, leaving 586 eligible patients. Of these 586 women with primary breast cancer and no previous hysterectomy, 108 patients had received tamoxifen, 10 mg twice a day for greater than 1 year. Four of the 108 patients subsequently developed endometrial adenocarcinoma. Four hundred seventy-eight breast cancer patients did not receive tamoxifen and 4 later developed endometrial adenocarcinoma. The odds ratio for the development of endometrial cancer when exposed to tamoxifen was 15.2 with a 95% confidence interval of 2.8-84.4. The patients exposed and not exposed to tamoxifen were compared for potential confounding variables and after controlling for the potential confounders, tamoxifen was found to be an independent risk factor for the development of endometrial cancer. CONCLUSIONS: Low-dose tamoxifen when given for greater than 1 year is associated with secondary endometrial cancer in patients with primary breast cancer.

Concentration guidelines for parenteral antibiotics in fluid-restricted patients.

A guideline for the preparation of peripherally administered antibiotics in fluid-restricted patients was developed. A maximum osmolality of 560 mOsmol/kg was selected since this corresponds to the theoretical osmolality of dextrose 5% in NaCl 0.9%, a solution commonly administered peripherally without significant incidence of phlebitis. Percentage concentrations corresponding to 560 mOsmol/kg of 26 intravenous antibiotics were calculated using sodium chloride equivalents. The antibiotics were reconstituted using sterile water, dextrose 5%, and NaCl 0.9% to provide an osmolality of 560 mOsmol/kg. The resulting solutions were measured for osmolality using a freezing-point depression osmometer. A total of 78 solutions were prepared and measured in triplicate. Of the 78 measured osmolalities, 67 (86 percent) were within 20 percent of the desired 560 mOsmol/kg. Only two osmolalities were more than 10 percent above the projected value. The percentage concentrations of 26 antibiotics in three solutions corresponding to 560 mOsmol/kg are presented. A method is also provided for tailoring concentrations to achieve desired osmolalities other than 560 mOsmol/kg.