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Extrapolating from toxicity data to occupational exposure limits: some considerations.

This paper evaluates procedures relevant to extrapolating from toxicity data in man and animals to Occupational Exposure Limits. It examines effects at or around the "No Observed Adverse Effect Level' (NOAEL) and the magnitude of safety factors which can be applied in developing occupational exposure limits for non-stochastic effects. The relationship between incidence of stochastic effect and occupational exposure limit is also discussed.

Clinical Protocols

On randomized controlled trials and lifestyle interventions.

Randomized controlled trials (RCT) are viewed as the ultimate method for evaluation. The author claims that RCT do not enable full evaluation of lifestyle interventions in particular. Lifestyle interventions usually affect several diseases not measured by RCTs and the people who have undergone these interventions also have an impact on the lifestyle in their immediate environment. These potential biases indicate that RCTs underestimate the value of lifestyle interventions.

Bias

Differential response to early nutrition supplementation: long-term effects on height at adolescence.

BACKGROUND: The classical risk approach to predicting who benefits from an intervention is unsound because it relies on the theoretical assumption that those at risk will necessarily benefit. A better approach to systematically test who benefits from nutrition supplementation is proposed using interactive models. METHODS: Differential effects of nutrition supplementation during early childhood on stature at adolescence were studied in 245 males and 215 females to identify determinants of long-term benefit from food supplementation. Factors studied included family socioeconomic status (SES) and children's home diet and diarrhoea during the first 3 years of life. To determine whether a factor conferred benefit, the statistical significance of the interaction between this factor and the intervention was tested. Data from the INCAP supplementation trial in Guatemala and from the follow-up of the same subjects at adolescence were used. RESULTS: Ordinary least squares (OLS) showed that high rates of diarrhoea in males and poor SES in females were significant determinants of benefit from supplementation at adolescence, and that the effects were mediated by length at 3 years old. Results of two-stage least squares (2SLS) analysis showed that length at 36 months, maturation and maternal height were significant determinants of height at adolescence but SES was not. CONCLUSIONS: Nutrition supplementation in early childhood has long-lasting effects on body size and the larger benefits acquired by some groups of children remain throughout early adulthood. The relevance of these findings for screening and targeting of nutritional interventions is discussed.

Adolescent

Aging and total cholesterol levels: cohort, period, and survivorship effects.

This analysis describes the association of age with the serum total cholesterol level in 5,010 participants in a geriatric health screening program. Cholesterol levels were measured annually in participants monitored for up to 12 years. The association of age with cholesterol level is described via three approaches: cross-sectional analysis, descriptive longitudinal analysis, and longitudinal analysis using statistical modeling. The results were compared to examine the influence of cohort, period, and survivorship effects on the association between age and cholesterol. In cross-sectional analysis, the cholesterol level was fairly constant for the ages of 65 to 75 years, but decreased by 21% over the age range from 75 to 95 years. Descriptive longitudinal analysis suggested that both cohort and period effects were influencing the cross-sectional findings. In longitudinal analysis adjusting for both cohort and period effects, the findings were similar to those from cross-sectional analysis for the ages of 65 to 75 years, but from the ages of 75 to 95 years, cholesterol decreased by only 9%--half as great a decline as that estimated from cross-sectional analysis. When longitudinal data were limited to those with complete follow-up, the predicted decline for the age range from 75 to 95 years was only 6%. Although this flattening of the age trend was suggestive, there was no conclusive evidence that it reflected an association between baseline cholesterol and loss to follow-up.

Age Factors

Efficacy of comprehensive rehabilitation programs and back school for patients with low back pain: a meta-analysis.

BACKGROUND AND PURPOSE: The use of back school as a treatment for low back pain is widespread, but determining the efficacy of this approach is complicated by variations in back schools and study methods across clinical trials. The purpose of this study was to conduct a meta-analysis to synthesize existing evidence on the efficacy of back school as either a primary intervention or a part of a comprehensive rehabilitation program for patients with low back pain. METHODS: The results of 19 prospective randomized controlled trials were evaluated. Quantitative reviewing procedures were used to calculate the effect sizes that compared patients receiving back school with those in a control or comparison group. Effect sizes were computed for 206 hypothesis tests involving 2,373 patients. RESULTS: The average effect size for comprehensive rehabilitation programs that included back school (d = 0.28) was larger than the average effect size for programs that offered back school as the primary intervention (d = -0.14). When effect sizes were stratified by program type and outcome, the comprehensive programs were superior to primary back school programs with respect to pain reduction, increased spinal mobility, and increased strength. Both types of programs showed reasonable success with education/compliance outcomes (d = 0.27-0.28). Lower effect sizes were found among the types of programs for disability and work/vocational outcomes (d < or = 0.20). CONCLUSIONS AND DISCUSSION: Back schools were most efficacious when coupled with a comprehensive rehabilitation program. Efficacy was supported for the treatment of pain and physical impairments and for education/compliance outcomes. Work/vocational and disability outcomes, however, were not improved substantially beyond control levels in comprehensive or primary back school programs. [Di Fabio RP. Efficacy of comprehensive rehabilitation programs and back school for patients with low back pain: a meta-analysis.

Comprehensive Health Care

Tap or bottled water consumption and spontaneous abortion: a 1986 case-control study in California.

To investigate whether drinking tap or bottled water during pregnancy affects the risk of spontaneous abortion, we asked questions about water consumption in a large case-control study (626 cases, 1,300 controls). The study ascertained cases from hospital pathology laboratory reports of pregnancies that began in 1986 and obtained controls from birth certificates. The crude odds ratio for consumption of any vs no cold tapwater at home during the first trimester was 1.2 (95% confidence interval = 1.0-1.5), with no dose-response effect. The crude odds ratio for any bottled water consumption was 0.79 (95% confidence interval = 0.65-0.96), with a downward trend by amount consumed. Adjusting for many potential confounders did not alter these associations appreciably, although some variables appeared to be effect modifiers. The point estimates were stronger among women who were more difficult to contact, suggesting the possibility of bias.

Abortion, Spontaneous

Just another day in a woman's life? Part II: Nature and consistency of women's long-term memories of their first birth experiences.

Twenty women who attended the author's natural childbirth classes between 1968 and 1974 were the informants in this study of long-term memories of their first childbirths. The data from each informant consisted of 1) a labor and birth questionnaire, including an open-ended account of her labor, written shortly after her baby was born; 2) a similar questionnaire and account written in 1988 and 1989; and 3) a transcribed interview during which her memories and perceptions were discussed and any discrepancies between the questionnaires were explored. The questionnaires were compared for consistency of recall, and the interviews consulted for further clarification. Specific memories were excerpted, compared, classified, tabulated, and summarized. Findings were that, years later, women's memories are generally accurate, and many are strikingly vivid, especially of onset of labor; rupture of the membranes; arrival at the hospital; actions of doctors, nurses, and partners; particular interventions; the birth; and first contact with the baby. Most memory lapses or confusion were minor. Evidence of a halo effect was observed as well.

Adaptation, Psychological

Single-blind studies of the effects of improved periodontal health on metabolic control in type 1 diabetes mellitus.

Uncontrolled studies have suggested a beneficial effect of periodontal treatment on metabolic control of insulin-dependent diabetes mellitus (IDDM). We therefore conducted controlled single-blind studies, using current metabolic status indicators in IDDM subjects free of significant complications other than periodontal diseases. In the 1st study, 41 IDDM subjects with gingivitis and early periodontitis were randomly assigned to treatment (oral hygiene and scaling) or control groups. The study was completed by 16 experimental and 15 control subjects. Reassessment after 2 months showed a Hawthorne effect in the control group, and no difference between groups. However, further analysis showed a relationship between individual metabolic control variation and gingival inflammation. A 2nd study enrolled 23 IDDM subjects with advanced periodontitis, who were randomised to treatment (full initial therapy including root planning) or control groups. Only 1 subject failed to complete the study, owing to illness. In this study, a significant response to periodontal treatment was not accompanied by any improvement in metabolic control. These results support the concept that the effect of metabolic control may be predominant in the relationship between IDDM and periodontal health.

Adolescent

The effect of a five-month delay on children's and adults' eyewitness memory.

Child witnesses must endure a delay of around six months between observing or being the victim of an alleged offence and being required to give evidence in a criminal court. While the legal profession seem to believe that young children's memories are particularly sensitive to the passage of time, developmental psychology can offer little relevant data to support or refute this presumption. In the present study, children aged six and nine years and adults witnessed a staged event and were subsequently interviewed in the days following the event and/or five months later. Results indicate that while all witnesses forgot information over this period, the younger children (six years) recalled slightly less information than the older children and the adults. The total amount of incorrect information recalled did not increase over the same period. Two different interviewing techniques were used--cued recall vs. 'enhanced' recall--the latter incorporating some aspects of the cognitive interview procedure. No differences were found relating to the interview techniques employed. The results underline the importance of recording initial interviews with child witnesses wherever possible.

Adult

Postal survey on airborne occupational exposure and respiratory disorders in Norway: causes and consequences of non-response.

STUDY OBJECTIVE: The aim was to examine causes for non-response in a community survey, and how non-response influences prevalence estimates of some exposure and disease variables, and associations between the variables. DESIGN: This was a cross sectional questionnaire study with two reminder letters. The questionnaire asked for information on smoking habits, occupational airborne exposure and respiratory disorders. SETTING: A random sample of 4992 subjects from the general population aged 15-70 years of Hordaland County, Norway. MAIN RESULTS: The overall response rate was 90%, with a 63% response to the initial letter. The response rates to the first and second reminder letters were 56% and 36% respectively. In 20% of the non-respondents an uncompleted questionnaire was returned with cause for non-response; in two thirds of these the cause for non-response was that the subject was not resident at the mailing address. A home visit to a random sample of 50 urban non-respondents provided further information on 29 subjects. A wrong address at the Central Population Registry and the subject's feeling of lack of personal benefit from a postal survey were the major reasons for non-response. Smokers were late respondents and subjects with respiratory disorders tended to be early respondents. CONCLUSION: The main reasons for non-response were a wrong mailing address and a feeling of lack of personal benefit from responding. Using only the initial letter would have changed the estimated prevalence of smokers from 39% to 35%. Otherwise, the estimated prevalence of the exposure and disease variables as well as the associations between them were only slightly changed after including the respondents to the first and second reminder letters.

Adolescent

Investigating the proxy effect and the saliency principle in household based postal questionnaires.

STUDY OBJECTIVE: The aim was to investigate two possible sources of bias inherent in using a household based postal questionnaire, the "proxy effect", inaccurate reporting about characteristics of others, and the "saliency principle", reporting of only the most salient features. This is of importance in surveys concerned with screening the population to identify individuals with certain characteristics, and so possibly relying on one member of the household to reply on behalf of all others. DESIGN AND SETTING: A two stage survey of disablement in the population was undertaken. A first phase postal questionnaire was sent to 25,168 households in Calderdale, West Yorkshire, England, to ascertain the prevalence of physical disability and of troubles with the joints. The second phase comprised in depth interviews with a sample of individuals identified in the first phase as being disabled. RESPONDENTS: A total of 21,889 postal questionnaires were returned (87%) representing households containing 42,826 people aged 16 years and over. A disproportionately stratified random sample of 950 respondents reporting disability was taken in the second phase. Of these 891 were still available, and 838 (94%) were interviewed. MEASUREMENTS AND MAIN RESULTS: The postal questionnaire found that almost 29% of those who lived "alone" (without another adult) reported some level of disability, compared to only 10% of those who lived with others. The difference remained significant after standardisation. This apparent underreporting or "proxy effect" was present for reporting about disability overall, but not for severe disability (dependence on help of others), which suggests the operation of the "saliency principle". Reporting on joint troubles appeared to be affected by the proxy effect both for any joint problems, and when more than five joints were affected. Analysis of a small set of postal questionnaires from respondents who reported joint problems only at interview and where we could identify who had completed the postal questionnaire supports the hypothesis of a proxy effect; two thirds of the original postal questionnaires had been completed by a proxy. The results were further complicated by an interaction between reporting of disability and joint troubles: the greater the level of disability, the less likely the reporting of joint troubles. CONCLUSIONS: The findings have general implications for studies involving postal household screening questionnaires, and raises additional concerns about those that are multitopic in content. In surveys of symptoms and minor disability, a proxy effect is likely to be operative. This effect is not apparent for obvious and long standing problems such as dependence on others for help. However the interaction between the reporting of disability and joint symptoms carries important implications for the development of multitopic postal screening questionnaires.

Adolescent

The person-trade-off approach to valuing health care programs.

The person-trade-off technique is a way of estimating the social values of different health care interventions. Basically it consists in asking people how many outcomes of one kind they consider equivalent in social value to X outcomes of another kind. The paper outlines a number of the author's previous studies using the technique. The studies suggest that while the technique is theoretically appealing for resource-allocation purposes, it is in practice quite demanding. It needs to be applied in fairly large groups of subjects to keep random measurement error at an acceptable level. Possible framing effects include the effects of argument presentation and the choice of start points in numerical exercises. To control for these effects, it seems important to take subjects through a multistep procedure, in which they are induced to carefully consider the various arguments that might be relevant in each exercise and to reconsider initial responses in the light of their implications. The investigator must also think through which decision context he or she wishes to study and make his or her choice of context very clear when reporting the results. In spite of these problems, the person-trade-off technique deserves greater attention in the field of cost-utility analysis.

Bias

Assessing preferences about the DNR order: does it depend on how you ask?

Despite increasing emphasis on advance directives, there has been little methodologic work to assess preferences about the "do not resuscitate" (DNR) order. This developmental work assessed, in a non-patient group, the performance of a probability-trade-off task designed to assess DNR attitudes, in terms of framing effects and stability of preferences. 105 female nursing students each completed one of two versions of the task. In version I (n = 58), the trade-off moved to increasingly negative descriptions of the outcomes of resuscitation (decreasing chance of survival and increasing risk of brain death), whereas in version II (n = 47), the trade-off moved to increasingly positive descriptions. One week later, repeat assessments were obtained for versions I (n = 35) and II (n = 28). The DNR preference scores were lower and more stable when the task moved to increasingly positive descriptions; perhaps this version of the task tends to weaken risk aversion. These results imply that care should be used in applying a probability trade-off task to the assessment of DNR preferences, since artefactual effects could be induced.

Attitude to Health

Clinical evaluation of the rocker bottom crutch.

One hundred fifty hospitalized patients referred to a physical therapy department for crutch walking instruction were evaluated in a randomized, controlled crossover study with "rocker bottom" and conventional axillary crutches. A large training effect was observed with each crutch, but no significant differences (all P greater than .05) of gait speed, stride length, heart rate, stability, or feeling of security were noted between the groups. Thus, rocker bottom crutches, despite potential stability and energy conservation benefits, were found to be no more effective than conventional axillary crutches in this hospital setting.

Aged

Synthesis of research findings through meta-analysis.

Meta-analysis is an alternative, quantitative approach to the analysis and synthesis of multiple investigations of the same clinical question. The statistical approaches that have been developed since Glass coined the term meta-analysis in 1976 are discussed. Clinicians will find meta-analysis helpful when there are conflicting research findings about perplexing clinical problems.

Bias

The effects of cluster sampling in an African urban setting.

Cluster sampling was popularised by the sampling procedure promoted by the WHO/UNICEF for the evaluation of the expanded programme of immunisation (EPI). Without a clear understanding of the limitations of the sampling strategy used, this sampling strategy has been extended to other types of surveys. This article shows how to approach the assessment of cluster sampling techniques scientifically by calculating design effects (DEFFs) and rates of homogeneity (roh) and illustrates this scientific assessment with three case studies from Alexandra in South Africa. We report on the DEFFs and rohs for variables studied in these surveys. The DEFF for all the variables relating to housing tended to exceed two and was as high as 6.99 for the variable new development. The variables relating to health service utilisation and health practices, namely immunisation status, nutrition status, presence of Road to Health Cards (RTDCs), breast-feeding and knowledge of diarrhoea and oral rehydration all had a DEFF close to one. The variables relating to contraception use, literacy and schooling had DEFFs close to one and a half. For a few variables the DEFFs were below one and the rates of homogeneity less than zero. The highest values of roh were for environment factors (all above 0.1433). Rohs for factors related to utilization of PHC services were mostly between 0.0200 and 0.0499. No single class of factors seemed to be related to very low values of roh. These results are then discussed.

Cluster Analysis