Effect of maternal and infant covariates on sibship correlation in birth weight

Birth weight on 12,644 singleton infants from 6,196 sibships born in Maryland between 1980 and 1984 were used to estimate the effects of nine maternal and infant covariates on the sibship correlation in birth weight. Assuming a homogeneous correlation across all families, the estimated intraclass correlation was 0.4664 (+/- 0.0099). This high sibship correlation makes it possible to predict, with reasonable accuracy, the birth weight of a child given information on previous sibs, as well as covariates on the mother and/or infant pertinent to a given pregnancy. The reduction in variance associated with incorporating information on the nine covariates used here was approximately equal to that obtained by conditioning on a single previous sib. Testing for heterogeneity in correlation among different groups of families showed that a crude measure of parity (first live birth vs. other), time between births, mother's marital status, and maternal age at the birth of the last child significantly influenced the sibship correlation in birth weight.     

Clinical trials seen shifting overseas.

A Tufts University study released in mid-2003 indicates that increasing numbers of clinical trials for U.S.-produced pharmaceutical are being conducted outside the United States, mainly by contract research organizations. This process speeds up clinical trials, but raises ethical issues of the possible coercion or exploitation of more vulnerable and naive patient populations.     

Sustainability of pyrethroid-impregnated bednets for malaria control in Afghan communities.

Between 1992 and 1995 a series of studies was undertaken to assess the long-term suitability of pyrethroid-impregnated bednets (PIBs) for malaria control in Afghan refugee communities in two villages in North-West Frontier Province, Pakistan. During 1992, 86% of bednet owners volunteered to have their bednets re-impregnated, and a further 15% of families purchased nets at two-thirds of cost price. From 1992 onwards, 27% of the villagers returned to Afghanistan, and annual house spraying campaigns were introduced to protect those still resident but sleeping without bednets. Within 3 years, these campaigns, together with PIBs, reduced the annual incidence of malaria by 87%, from 597 to 78 cases per 1000 population. Nevertheless, 65% of resident families continued to re-impregnate their nets annually with permethrin. To assess whether PIBs were still being used and were still protective, in view of these reduced transmission rates, we carried out a case--control study in 1994 on febrile or otherwise symptomatic patients presenting at village health centres. Comparison of the slide-positivity rates of PIB users and those without bednets showed that regular usage reduced the odds of contracting falciparum and vivax malaria to 0.22 (95% confidence interval (CI): 0.09-0.55) and 0.31 (95% CI: 0.19-0.51), respectively. There was no evidence of a sex- or age-bias in bednet use or in protective effect. The results indicate that a community-based PIB programme is an appropriate malaria control measure in areas where management or security problems make traditional house-spraying campaigns impossible. A relevant finding for those involved in the monitoring of bednet distribution projects is that the local coverage of bednets and the local impact on malaria, even when introduced to remote areas, can be estimated very cheaply by health centre microscopists who simply catalogue blood film diagnoses according to patients'' bednet use practices.     

FEASIBILITY OF CONDUCTING CARDIOVASCULAR OUTCOME RESEARCH IN AUSTRALIAN GENERAL PRACTICE: RESULTS FROM THE ANBP2 PILOT STUDY

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.     

Effects of risk-associated human dietary macrocomponents on processes related to carcinogenesis in human-flora-associated (HFA) rats

Dietary fat, beef protein and fibre have been shown to modulatecancer risk in humans and the present study examined the biologicaleffects in human-flora-associated (HFA) rats of altering intakelevels within the normal human range. Two control groups, oneHFA and the other germfree (GF), consumed a human diet low infat, fibre and beef for 4 weeks; three other groups consumedhuman diets similar except for independent 3-fold increasesin fat, beef protein or fibre. After 2 weeks on the diets, magneticallyrecoverable microcapsules were given orally to the rats andsubsequently recovered from the faeces to assess endogenouscross-linking agents. After 4 weeks, measurements were madeof gut microfloral enzyme activities, hepatic activation ofdietary mutagens and hepatic DNA adducts by ³²P-postlabelling.Activation in vitro of the dietary mutagens 2-amino-3-methyl-3H-imidazo[4,5-f]quinolline (IQ) and 2-amino-l-methyl-6- phenytimidazo[4,5-b]pyridine(PhIP) by hepatic S9, formation of endogenous hepatic DNA adductsin vivo and the ß-glucuronidase activity of caecalcontents were all increased in the sequence high fat > highfibre > high beef = control. Of the two DNA adducts foundin all HFA rats, only one was present in GF controls, indicatingthat the human gut microflora (subject to human dietary modulation)either releases a DNA-adducting product able to act outsidethe gastrointestinal tract, or stimulates the generation ofsuch a product by mammalian processes. Caecal nitrate reductaseactivity was highest in rats fed the high beef diet, whilstentrapment of cross-linking agents was highest in those fedthe high fibre diet. These results show that risk-related componentsof human diets interact with human gut microflora to modulatethe production of endogenous DNA-adducting and cross-linkingsubstances.