Rosemary F. Head

Cardiovascular disease in a cohort exposed to the 1940–45 Channel Islands occupation

BackgroundTo clarify the nature of the relationship between food deprivation/undernutrition during pre- and postnatal development and cardiovascular disease (CVD) in later life, this study examined the relationship between birth weight (as a marker of prenatal nutrition) and the incidence of hospital admissions for CVD from 1997–2005 amongst 873 Guernsey islanders (born in 1923–1937), 225 of whom had been exposed to food deprivation as children, adolescents or young adults (i.e. postnatal undernutrition) during the 1940–45 German occupation of the Channel Islands, and 648 of whom had left or been evacuated from the islands before the occupation began.MethodsThree sets of Cox regression models were used to investigate (A) the relationship between birth weight and CVD, (B) the relationship between postnatal exposure to the occupation and CVD and (C) any interaction between birth weight, postnatal exposure to the occupation and CVD. These models also tested for any interactions between birth weight and sex, and postnatal exposure to the occupation and parish of residence at birth (as a marker of parish residence during the occupation and related variation in the severity of food deprivation).ResultsThe first set of models (A) found no relationship between birth weight and CVD even after adjustment for potential confounders (hazard ratio (HR) per kg increase in birth weight: 1.12; 95% confidence intervals (CI): 0.70 – 1.78), and there was no significant interaction between birth weight and sex (p = 0.60). The second set of models (B) found a significant relationship between postnatal exposure to the occupation and CVD after adjustment for potential confounders (HR for exposed vs. unexposed group: 2.52; 95% CI: 1.54 – 4.13), as well as a significant interaction between postnatal exposure to the occupation and parish of residence at birth (p = 0.01), such that those born in urban parishes (where food deprivation was worst) had a greater HR for CVD than those born in rural parishes. The third model (C) found no interaction between birth weight and exposure to the occupation (p = 0.43).ConclusionThese findings suggest that the levels of postnatal undernutrition experienced by children, adolescents and young adults exposed to food deprivation during the 1940–45 occupation of the Channel Islands were a more important determinant of CVD in later life than the levels of prenatal undernutrition experienced in utero prior to the occupation.

Flaws in the U.S. Food and Drug Administration’s Rationale for Supporting the Development and Approval of BiDil as a Treatment for Heart Failure Only in Black Patients

The U.S. Food and Drug Administrations (FDA) rationale for supporting the development and approval of BiDil (a combination of hydralazine hydrochloride and isosorbide dinitrate; H-I) for heart failure specifically in black patients was based on under-powered, post hoc subgroup analyses of two relatively old trials (V-HeFT I and II), which were further complicated by substantial covariate imbalances between racial groups. Indeed, the only statistically significant difference observed between black and white patients was found without any adjustment for potential confounders in samples that were unlikely to have been adequately randomized. Meanwhile, because the accepted baseline therapy for heart failure has substantially improved since these trials took place, their results cannot be combined with data from the more recent trial (A-HeFT) amongst black patients alone. There is therefore little scientific evidence to support the approval of BiDil only for use in black patients, and the FDAs rationale fails to consider the ethical consequences of recognizing racial categories as valid markers of innate biological difference, and permitting the development of group-specific therapies that are subject to commercial incentives rather than scientific evidence or therapeutic imperatives. This paper reviews the limitations in the scientific evidence used to support the approval of BiDil only for use in black patients; calls for further analysis of the V-HeFT I and II data which might clarify whether responses to H-I vary by race; and evaluates the consequences of commercial incentives to develop racialized medicines. We recommend that the FDA revise the procedures they use to examine applications for race-based therapies to ensure that these are based on robust scientific claims and do not undermine the aims of the 1992 Revitalization Act.

A qualitative exploration of the production of Hospital Episode Statistics in a Guernsey hospital: implications for regional comparisons of UK health data

Hospital Episode Statistics (HES) are widely used in the UK for audit and research. This often includes comparisons between different geographical regions, but there is some doubt as to the reliability of comparisons made using these data. Previous studies have focused on the quantitative accuracy of the coding, but not the full data chain. This study is a qualitative examination of the production of HES in a small hospital in Guernsey, which is not part of the NHS. Interviews were conducted with key participants in the production of HES to determine how the data were created, and the strengths and weaknesses of this system. We found that face-to-face communication between administrative and clinical staff was felt to contribute to the accuracy of the HES codes, and that a lack of detail in the case-notes was felt to be more problematic than the accuracy of the coders themselves. These findings have implications for the comparison of HES between NHS Trusts, since the processes involved in producing the data will be different in larger hospitals with less contact between coders and clinicians. It is therefore important to bear this in mind when making comparisons between such diverse sources of HES.

CHOLESTEROL LEVELS IN LATER LIFE AMONGST UK CHANNEL ISLANDERS EXPOSED TO THE 1940-45 GERMAN OCCUPATION AS CHILDREN, ADOLESCENTS AND YOUNG ADULTS

Background: To clarify the nature of the relationship between: food deprivation and undernutrition during pre- and postnatal development; and cholesterol levels in later life, this study examined the relationship between birth weight (as a marker of prenatal nutrition) and cholesterol levels among 396 Guernsey islanders (born in 1923–1937), 87 of whom (22%) had been exposed to food deprivation as children, adolescents or young adults (i.e. to postnatal undernutrition) during the 1940–45 German occupation of the Channel Islands, and 309 of Whom (78%) had left or been evacuated from the islands before the occupation began. Methods: Three sets of multiple regression models were used to investigate: Model A — the relationship between birth weight and cholesterol levels; Model B — the relationship between postnatal exposure to the occupation and cholesterol levels; and Model C — any interaction between birth weight, postnatal exposure to the occupation and cholesterol levels. Model A and Model B also tested for any interactions between: birth weight/occupation exposure and sex; and birth weight/occupation exposure and parish of residence at birth (as a marker of parish of residence during the occupation and related variation in the severity of food deprivation). Results: Before (and after) adjusting for potential confounders, no statistically significant relationships were observed between either birth weight (before adjustment: 0.09mmol/1 per kg increase, 95% CI: −0.30, 0.16; after adjustment: 0.08mmol/1 per kg increase, 95%CI: −0.17, 0.34) or exposure to the occupation (before adjustment: 0.01 mmol/l for exposed group, 95%CI: −0.24, 0.27; after adjustment: 0.041llmol/1 for exposed group, 95%CI: −0.26, 0.33) and cholesterol levels in later life. There was also little evidence of significant relationships between birth weight, exposure to the occupation and cholesterol levels in later life when Model A and Model B were stratified by sex or parish of residence at birth, although there was a significant positive relationship between birth weight and cholesterol levels in women (0.44mmol/1 per kg increase, 95%CI: 0.07, 0.81). Conclusions: These analyses provide little support for the theory that birth weight is inversely related to cholesterol levels in later life, and do not offer any evidence in support of a relationship between undernutrition in childhood, adolescence and early adulthood and cholesterol levels in later life. However, further research may determine whether undernutrition at different stages of the life-course may influence cholesterol levels in later life.

What evidence is there that adjustment for adult height influences the relationship between birth weight and blood pressure

Background: The inverse association between birth weight and blood pressure may partly be the result of inappropriate adjustment for adult body size, but it remains unclear whether adjustment for adult height elicits this effect. Aim: The study investigated the impact of adjustment for adult height on the relationship between birth weight and blood pressure. Methods: A systematic search of Medline® from 1996 to 2006 was conducted using the terms ‘birth weight’, ‘blood pressure’ and ‘hypertension’, and any papers containing linear regression analyses of blood pressure on birth weight for populations with an average age of 25+ were eligible for inclusion in comparative meta-analyses. Results: None of the 30 studies identified had published regression coefficients for blood pressure on birth weight before and after adjustment for adult height, and only two studies were found to adjust for adult height at all. Data from these studies were obtained, and it was found that adjustment for height made the association between birth weight and systolic blood pressure (SBP) more negative in one study but less negative in the other. When compared with meta-analyses of comparable models, it was found that both studies were substantially different from the combined estimate of the relationship between birth weight and SBP. Conclusions: Both the differences between the two selected studies and their differences from the combined estimates obtained by meta-analysis are likely to be due to differences in the age of the participants. The relationship between birth weight and SBP tended to become more strongly inverse in studies with older participants. Additionally, the correlations between height and SBP were found to change from positive to negative with increasing age, which explained the differential impact of adjustment for height in the two selected studies. It therefore appears that adjustment for height may have little effect for older participants, but more so for younger participants.