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Biomedical subjects

S Frankel

Publications and source records attributed to S Frankel.

At least 19 recordsLinked to original sources

Childhood housing conditions and later mortality in the Boyd Orr cohort.

STUDY OBJECTIVES: To examine associations between five measures of housing conditions during childhood and subsequent mortality from all causes, coronary heart disease, stroke, and cancer. DESIGN: Historical cohort study. SETTING: Data on housing conditions were collected from survey centres in 16 areas of England and Scotland. PARTICIPANTS: Children of families participating in the Carnegie Survey of Family Diet and Health in pre-war Britain (1937-1939). Analyses are based on a subset of 4168 people who were traced and alive on 1 January 1948. MAIN RESULTS: Poorer housing conditions were generally associated with increased adult mortality. After adjustment for childhood and adult socioeconomic factors, statistically significant associations were only found between lack of private indoor tapped water supply and increased mortality from coronary heart disease (hazard ratio 1.73, (95% CI 1.13, 2.64); and between poor ventilation and overall mortality (hazard ratio for people from households with poorest ventilation relative to best ventilation 1.30, 95% CI 0.97, 1.74). CONCLUSIONS: This study provides evidence that associations between housing conditions in childhood and mortality from common diseases in adulthood are not strong, but are in some respects distinguishable from those of social deprivation.

Adult↗

Method availability and the prevention of suicide--a re-analysis of secular trends in England and Wales 1950-1975.

BACKGROUND: In England and Wales in the 1960s there were marked declines in suicide rates. These reductions were partly attributable to the detoxification of the domestic gas supplies; however, their extent varied by age and gender, with the most striking effects seen in older men. The objective of this study was to investigate method-specific trends in suicide between 1950 and 1975 to elucidate possible explanations for the patterns seen in different demographic groups. METHODS: An analysis of age-standardised method-specific suicide rates for England and Wales between 1950 and 1975 was carried out using routinely available mortality and population statistics. RESULTS: As has previously been shown, there were marked reductions in suicides by gassing in men and women of all ages between 1960 and 1975. In women and younger men, the effects of these reductions on overall suicide rates were partially offset by rises in drug overdose deaths (method substitution), but there were no immediate increases in the use of other suicide methods. In contrast, in older men, reductions in suicide by gassing were accompanied by only a slight increase in overdose suicides as well as reductions in rates of suicide using all other methods. The modest rise in overdose fatalities in older men occurred despite the fact that they were more often prescribed barbiturates and tricyclic antidepressants than younger men. CONCLUSIONS: Accessibility to and the lethality of particular methods of suicide may have profound effects on overall suicide rates. Such effects appear to depend upon the popularity of the method and the extent to which alternative methods that are acceptable to the individual are available. Social and psychological interpretations of fluctuations in suicide rates should only be made after assessing the possible contribution to these of changes in method availability and lethality.

Adolescent↗

Hydroxychloroquine for the treatment of chronic graft-versus-host disease.

Chronic graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation. Both the disease and the medications used to treat it are associated with significant morbidity and mortality. The manifestations of chronic GVHD often resemble those of autoimmune disorders. Hydroxychloroquine (HCQ) is a 4-aminoquinoline antimalarial drug used for the treatment of autoimmune diseases. HCQ interferes with antigen processing and presentation, cytokine production, and cytotoxicity and is synergistic with cyclosporine and tacrolimus in vitro. Forty patients with steroid-resistant or steroid-dependent chronic GVHD were enrolled in a phase 2 trial of HCQ 800 mg (12 mg/kg) per day. Three complete responses and 14 partial responses were seen in 32 evaluable patients (53% response rate). All responders tolerated a >50% reduction in their steroid dose while receiving HCQ. Clinical response occurred at a median of 8 weeks (range, 4 to 24 weeks). No hematologic, hepatic, renal, or retinal toxicity was associated with HCQ. In light of its mechanisms of action, clinical activity for GVHD, and low toxicity profile, HCQ may be useful in a multiagent approach for the treatment of extensive chronic GVHD.

Adolescent↗

Transcutaneous immunization: a human vaccine delivery strategy using a patch.

Transcutaneous immunization, a topical vaccine application, combines the advantages of needle-free delivery while targeting the immunologically rich milieu of the skin. In animal studies, this simple technique induces robust systemic and mucosal antibodies against vaccine antigens. Here, we demonstrate safe application of a patch containing heat-labile enterotoxin (LT, derived from Escherichia coli) to humans, resulting in robust LT-antibody responses. These findings indicate that TCI is feasible for human immunization, and suggest that TCI may enhance efficacy as well as improve vaccine delivery.

Administration, Cutaneous↗

Use of PEG-rHuMGDF in platelet engraftment after autologous stem cell transplantation.

This paper summarizes a pilot, sequential dose-escalation study of PEG-rHuMGDF in patients with advanced malignancies who had delayed platelet recovery after autologous stem cell transplantation (ASCT). Patients were randomized to receive either placebo (n = 11) or PEG-rHuMGDF at 5 (n = 9), 10 (n = 6), or 25 (n = 7) microg/kg/day by subcutaneous injection for 14 days and were monitored for 5 weeks. Across all treatment groups, eight patients had platelet recovery to > or = 20 x 10(9)/l by day 21. The proportion of patients achieving platelet recovery, the median number of days and units of platelet transfusions were similar for the placebo and the PEG-rHuMGDF groups. PEG-rHuMGDF was well tolerated at all dosages. The incidence rates of adverse events in all groups were similar. No deaths on study, no drug-related serious adverse events, and no development of neutralizing antibodies to MGDF occurred.

Adult↗

The effects of dietary supplementation on growth and adult mortality: a re-analysis and follow-up of a pre-war study.

The aim of this study was to re-analyse a diet supplementation study conducted in the 1930s and investigate the effects of food supplementation on children's growth and later adult mortality. A non-randomised controlled trial was carried out in eight of the sixteen centres participating in the Carnegie Survey of Diet and Health in pre-war Britain (1937-39). Food supplements were given for 12 months either at school or as food parcels sent to the family home. 545 children aged 2-14 received food supplements and 494 children of a similar age acted as their controls. The children came from 465 families. The increase in childhood height and its components-leg length and trunk length-over 12 months follow-up were measured. Mortality from all causes over 60 years follow-up to 1998 was also assessed. There were important differences between fed and control children at baseline. Supplemented children came from larger families with poorer diets and most were examined, on average, 12 days later than control children. After adjustment for baseline imbalances those receiving supplements increased in height by 3.7 mm (95% CI 1.9-5.5) more than the controls. After adjustment, most of the difference in growth appeared to arise as a result of increases in leg length. After adjustment for confounding factors measured in childhood, no significant effect of childhood food supplements on adult mortality was seen. The age-adjusted hazard ratio for all cause mortality was higher in the supplemented compared to control subjects: 1.13 95% CI (0.77-1.64). We found that provision of childhood food supplements led to increased growth amongst supplemented children. The increases in height in this study were mainly as a result of increases in leg length and are similar to those found in a more recent randomised trial in South Wales. Whilst other analyses suggest that childhood height is important in predicting adult mortality patterns, we found no significant effect of childhood food supplements on adult mortality patterns in this study, although the study lacked statistical power to detect small but, nevertheless, important differences in mortality. Larger randomised trials with long term follow-up would be required to investigate the impact of childhood food supplementation on adult health.

Adolescent↗

How accurately are height, weight and leg length reported by the elderly, and how closely are they related to measurements recorded in childhood?

BACKGROUND: This paper examines (1) the accuracy of self-reported height, leg length and weight in a group of subjects aged 56-78; (2) whether recent measurement of height and weight influences the accuracy of self-reporting and (3) associations between childhood and adult height, leg length and BMI measured in old age. METHODS: All 3182 surviving members of the Boyd Orr cohort were sent postal questionnaires in 1997-1998 and a sub-sample (294) was also clinically examined. RESULTS: Self-reported height was overestimated and body mass index (BMI), based on reported height and weight, underestimated. The mean difference between self-report and measured values were for height: 2.1 cm in males and 1.7 cm in females; for BMI the difference was -1.3 kg/m(2) in males and -1.2 kg/m(2) in females. Shorter individuals and older subjects tended to over-report their height more than others. The overweight under-reported their weight to a greater extent. Recent measurement appeared to decrease over-reporting of height but not weight. Correlations between self-report and measured height and BMI were generally over 0.90, but weaker for leg length (r = 0.70 in males and 0.71 in females). Adult height and leg length were quite closely related to their relative values in childhood (correlation coefficients ranged from 0.66 to 0.84), but associations between adult and childhood BMI were weak (r = 0.19 in males and 0.21 in females). CONCLUSIONS: Self-reported measures of height and weight may be used in studies of the elderly although systematic reporting errors may bias effect estimates. As overweight individuals tend to under-report and the short and underweight tend to over-report, studies investigating associations of disease with height and weight using self-reported measures will underestimate effects. The weak associations between childhood and adult BMI indicate that associations between childhood adiposity and adult cardiovascular disease found in this cohort may reflect the specific effect of childhood overweight, rather than its persistence into adulthood. This suggests that avoidance of adiposity may be as important in childhood as in adulthood.

Aged↗

Childhood socioeconomic position and adult cardiovascular mortality: the Boyd Orr Cohort.

The relation between childhood socioeconomic position and adult cardiovascular mortality is examined in 3,750 individuals whose families took part in the Carnegie survey of family diet and health in England and Scotland between 1937 and 1939. The trend in coronary heart disease mortality across social position groups was not statistically significant at conventional levels (p = 0.12), while a strong linear trend was seen for stroke mortality (p = 0.01). Adjustment for the Townsend deprivation index of area of residence during adult life did not materially alter these findings, indicating that the effects of socioeconomic influences upon particular cardiovascular diseases differ according to the age at which they are experienced.

Age of Onset↗

Population requirement for primary hip-replacement surgery: a cross-sectional study.

BACKGROUND: There has been a long-standing failure in many countries to satisfy the demand for several elective surgical treatments, including total hip replacement. We set out to estimate the population requirement for primary total hip replacement in England. METHODS: We undertook a cross-sectional study of a stratified random sample of 28,080 individuals aged 35 and over from 40 general practices in inner-city, urban, and rural areas of Avon and Somerset, UK. Prevalent disease was identified through a two-stage process: a self-report screening questionnaire (22,978 of 26,046 responded) and subsequent clinical examination. Incident disease was estimated from the point prevalence by statistical modelling. The requirement for total hip replacement surgery was estimated on the basis of pain and loss of functional ability, with adjustment for evidence of comorbidity and patients' treatment preferences. FINDINGS: 3169 people reported hip pain on the screening questionnaire. 2018 were invited for clinical examination, and 1405 attended. The prevalence of self-reported hip pain was 107 per 1000 (95% CI 101-113) for men and 173 per 1000 (166-180) for women. The prevalence of hip disease severe enough to require surgery was 15.2 (12.7-17.8) per 1000 aged 35-85 years. The corresponding annual incidence of hip disease requiring surgery was estimated as 2.23 (1.56-2.90), which suggests an overall requirement in England of 46,600 operations per year for patients who expressed a preference for, and were suitable for, surgery; the recent actual provision in England was about 43,500. INTERPRETATION: This research suggests that the satisfaction of demand for total hip replacement, given agreed criteria for surgery, is a realistic objective.

Adult↗