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PubMed1995

Procedural debiasing of primacy/anchoring effects in clinical-like judgments.

Primacy (or anchoring) effects in clinical judgment occur when information presented at an early stage unduly influences a judgment compared to the effect of the same information presented at a later stage. Using recent theoretical models of these effects, three debiasing methods were developed and tested for their efficacy. Contrary to some recent failures to find anchoring effects, both single-cue and sequence anchoring manipulations produced medium-size effects on personality trait ratings and generalized to predictions of behavior. A consider-the-opposite procedure that involved cue sorting by diagnosticity debiased single-cue anchoring, but comparable results were obtained by subjects who simply took notes while reviewing each cue prior to judgment. Bias inoculation was marginally successful at reducing single-cue anchoring. Methodological issues as well as suggestions for future research are discussed.

Analysis of Variance↗
PubMed2000

Health services utilization of elderly Swiss: evidence from panel data.

The demand for health care services by the elderly is a topic of growing importance because of changes in the demographic structure in many countries. This paper provides estimates of the determinants of the demand for physician visits by the elderly, including the impact of a disability prevention intervention. We control for unobserved heterogeneity across individuals and the count data structure of the data by estimating random effects negative binomial models for all primary physician and specialist visits.

Aged↗
PubMed1999

Comparison of the responsiveness and relative effect size of the western Ontario and McMaster Universities Osteoarthritis Index and the short-form Medical Outcomes Study Survey in a randomized, clinical trial of osteoarthritis patients.

OBJECTIVE: This study compares the responsiveness and relative effect sizes of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) with the Medical Outcomes Study Short Form Health Survey (SF-36) in a randomized clinical trial for treatment of osteoarthritis (OA). METHODS: Patients with OA of the knee or hip were randomized to receive either placebo or 2,400 mg/day of ibuprofen for 28 days. Patients completed the WOMAC and SF-36 at baseline and days 7, 14, and 28 of the trial. RESULTS: Patients receiving ibuprofen showed significant improvement in WOMAC pain, physical functioning, and the total score, while improvement was detected only for bodily pain on the SF-36. The WOMAC detected significant differences between ibuprofen and placebo for pain and physical functioning, whereas the SF-36 detected differences for the bodily pain subscale. CONCLUSION: These results suggest the WOMAC has greater power to detect treatment differences than the SF-36, with respect to pain and physical functioning, in OA clinical trials.

Activities of Daily Living↗
PubMed2001

Biopsychosocial mediators and moderators of stress-health relationships in patients with recently diagnosed rheumatoid arthritis.

OBJECTIVE: To investigate the mediating and moderating roles of social support, coping, and physiological variables in the relationship between life events and health status. METHODS: Psychological and biological measurements were taken in 54 patients (38 women, 16 men, mean age +/- SD 56 +/-14.4 years) with recently diagnosed rheumatoid arthritis (RA). RESULTS: Life events were correlated with psychological distress, but not with disease activity. No mediators for the relationship of life events with psychological well-being and disease activity were observed. In 40 tests, 4 moderators were found: Problem-focused coping, perceived support, diastolic blood pressure, and total number of lymphocytes were moderators of the relationship between daily hassles and health status (P < or = 0.05). CONCLUSION: Our study provides limited support for the notion that the interactions of life stress with biopsychosocial variables have an impact on health. None of these variables were found to be crucial mediators of stress-health associations in recently diagnosed patients with RA, but some provocative evidence was given that biopsychosocial variables may have a minor impact on stress-health relationships.

Adaptation, Psychological↗
PubMedDate not supplied

Evidence on major gene control of cortical index in pedigree data from Middle Dalmatia, Croatia.

It was recently reported that the inheritance of the metacarpal cortical index (CI) in the Chuvashian population can be described in terms of a major gene (MG) model. By applying transmission probability tests, the hypothesis was accepted that not only baseline level of CI but also its sex-specific dependence on age were under control of the same putative large-effect gene. Using a pedigree sample from the population of the islands of Middle Dalmatia, Croatia (847 observed individuals in 278 pedigrees), data are presented to support the above findings. The following hypotheses were accepted: (i) inheritance of baseline CI in the Croatian population can be attributed to the effect of a MG responsible for about 42% of the variation; (ii) the same MG takes part in the control of the dependence of CI on age, particularly the age at onset of involutive bone changes (inflection point), and of the rate of decrease in CI with age (slope coefficient). Issues related to the assortative mating effect on CI and the determination of the most parsimonious model are discussed.

Adolescent↗
PubMed1995

Respiratory effects of chronic hydrogen sulfide exposure.

A cross-sectional study investigated whether the exposure of sewer workers to hydrogen sulfide (H2S) was associated with reduced lung function. Sixty-eight sewer workers and 60 water treatment workers performed spirometric tests. Job titles were used to classify the sewer workers according to presumed H2S exposure, and water treatment workers served as a comparison population presumed to have no occupational exposure to H2S. There was a statistically significant difference in mean FEV1/FVC values between sewer and water treatment workers of similar age, height, race, and smoking habits (-3.1, s.e. = 1.4). This deficit was greatest (-5.7, s.e. = 2.0) for sewer workers presumed to have high H2S exposure. Nonsmoking sewer workers presumed to have high H2S exposure achieved only 89% of their predicted FEV1/FVC value, whereas nonsmoking water treatment workers achieved nearly 98% of their predicted FEV1/FVC value. In conclusion, this study found evidence that chronic low level exposure to H2S may be associated with reduced lung function.

Adult↗
PubMed1992

Sensitivity to change of the health assessment questionnaire (HAQ) and other clinical and health status measures in rheumatoid arthritis: results of short-term clinical trials and observational studies versus long-term observational studies.

To obtain evidence concerning short-term and long-term efficacy of clinical and health status measures in rheumatoid arthritis (RA), we conducted two observational studies--a 6-month study of 233 patients receiving methotrexate and a 10-year study of 157 patients receiving multiple treatments in a rheumatic disease clinic. Results of the 6-month study yielded effect sizes for treatment similar to the meta-analyses reported by Felson [corrected] et al. (Arthritis Rheum 33:1449-1461, 1990) and the controlled trials of methotrexate reported by Weinblatt et al. (Arthritis Rheum 33:330-338, 1990), suggesting that observational studies provide valid measurements of treatment effect. The effect size for the Health Assessment Questionnaire (HAQ) was 0.5. By contrast, the 10-year study suggested that standard clinical variables changed little and were not useful in assessing RA outcome, while the effect size of the HAQ was -2.39. These data continue to underscore the differences between short-term trials and the long-term outcome of RA, and suggest an important place for the HAQ or similar instruments in all phases of RA evaluation and assessment.

Arthritis, Rheumatoid↗
PubMed2006

A note on robust inference from a conditional Poisson model.

A randomised controlled trial to evaluate a training programme for physician-patient communication required the analysis of paired count data. The impact of departures from the Poisson assumption when paired count data are analysed through use of a conditional likelihood is illustrated. A simple approach to providing robust inference is outlined and illustrated.

Algorithms↗
PubMed2006

An 'unconditional-like' structure for the conditional estimator of odds ratio from 2 x 2 tables.

In the estimation of the odds ratio (OR), the conditional maximum-likelihood estimate (cMLE) is preferred to the more readily computed unconditional one (uMLE). However, the exact cMLE does not have a closed form to help divine it from the uMLE or to understand in what circumstances the difference between the two is appreciable. Here, the cMLE is shown to have the same 'ratio of cross-products' structure as its unconditional counterpart, but with two of the cell frequencies augmented, so as to shrink the unconditional estimator towards unity. The augmentation involves a factor, similar to the finite population correction, derived from the minimum of the marginal totals.

Algorithms↗
PubMed2002

Davidson Trauma Scale (DTS): normative scores in the general population and effect sizes in placebo-controlled SSRI trials.

The Davidson Trauma Scale (DTS) was developed as a self-rating for use in diagnosing and measuring symptom severity and treatment outcome in post-traumatic stress disorder (PTSD); 630 subjects were identified by random digit dialing and evaluated for a history of trauma. Prevalence rates of PTSD and subthreshold PTSD with impairment were 2.2 and 4.1%, respectively. In this general population sample, 438 subjects endorsed at least one trauma, and four groups were generated: A) threshold PTSD (n = 13), B) subthreshold PTSD with impairment (n = 26), C) subthreshold PTSD without impairment (n = 78), and D) no PTSD (n = 321). Mean (SD) DTS score in the entire population was 11.0 +/- 18.1. Differences were found in four of the five pairwise between-group contrasts. In a second sample of 447 clinical trial participants from three SSRI vs. placebo studies, we assessed treatment effect size according to different measures. In all three clinical trials, effect size with the DTS was equal to, or better than, those found for the Impact of Event Scale (IES), Clinician Administered PTSD Scale (CAPS), and Structured Interview for PTSD (SIP). These results further affirm the utility of the DTS as a self-rating measure of PTSD symptom severity and in evaluating treatment response.

Adult↗
PubMed2003

Detecting genotype combinations that increase risk for disease: maternal-fetal genotype incompatibility test.

Biological mechanisms that involve gene-by-environment interactions have been hypothesized to explain susceptibility to complex familial disorders. Current research provides compelling evidence that one environmental factor, which acts prenatally to increase susceptibility, arises from a maternal-fetal genotype incompatibility. Because it is genetic in origin, a maternal-fetal incompatibility is one possible source of an adverse environment that can be detected in genetic analyses and precisely studied, even years after the adverse environment was present. Existing statistical models and tests for gene detection are not optimal or even appropriate for identifying maternal-fetal genotype incompatibility loci that may increase the risk for complex disorders. We describe a new test, the maternal-fetal genotype incompatibility (MFG) test, that can be used with case-parent triad data (affected individuals and their parents) to identify loci for which a maternal-fetal genotype incompatibility increases the risk for disease. The MFG test adapts a log-linear approach for case-parent triads in order to detect maternal-fetal genotype incompatibility at a candidate locus, and allows the incompatibility effects to be estimated separately from direct effects of either the maternal or the child's genotype. Through simulations of two biologically plausible maternal-fetal genotype incompatibility scenarios, we show that the type-I error rate of the MFG test is appropriate, that the estimated parameters are accurate, and that the test is powerful enough to detect a maternal-fetal genotype incompatibility of moderate effect size.

Bias↗
PubMed2003

Association mapping of complex diseases in linked regions: estimation of genetic effects and feasibility of testing rare variants.

Association mapping in linked regions is a current major approach for the identification of genes for complex diseases. Loci contributing to linkage, even with small values of sibling recurrence risk (lambda(s)), may be equivalent to substantial underlying genetic effects for association studies. For disease alleles with a frequency as low as 1%, highly reliable association studies (80% power for significance level alpha=10(-6)) require only 277, 781, and 1289 families or cases and controls for loci detected with lambda(s) of 1.5, 1.1, and 1.05, respectively, under a multiplicative genetic model. Under alternative models, provided epistatic effects are minor, larger achievable sample sizes will provide sufficient power to map almost any disease gene that may have initially contributed to linkage.

Bias↗
PubMed1994

Power of segregation analysis for detection of major gene effects on quantitative traits.

The power to detect major gene effects by rejection of the "no major gene" null hypothesis against a mixed model alternative was determined in random samples of nuclear families over a variety of conditions. Benchmarks have been developed using a varying number of families whose structure includes both parents and three children. Phenotypes were simulated assuming a Mendelian major gene under either recessive or dominant inheritance, with 0-30% residual polygenic heritability. Three trait prevalences--5, 10, and 20%--were considered in combination with increasing displacement between homozygous means, spanning a range of 14 to 36% of the phenotypic variance attributable to the major gene effect. All other assumptions of the traditional mixed model were adopted in the generating models. Segregation analysis was carried out on the simulated data sets and the proportion of samples out of 200 replications in which the null hypothesis q = 0 was rejected is reported as the power. Thus, failure to detect a major gene effect in this context is solely due to sampling variation, since no other perturbations were introduced. In general, there appears to be greater power to detect dominant major gene effects as opposed to recessive ones using otherwise comparable parameter values, and the effect of varying sibship size under dominant models appears to be greater as well. The use of joint vs. conditional likelihood calculations also was evaluated: substantial drops in power were observed when using conditional likelihoods under recessive inheritance, while the differences in power appeared to be nominal under dominant inheritance. The results of this investigation are offered as a guide to assist in the design of family studies whose aim is to detect major gene effects.

Bias↗
PubMed1995

Variation in HLA-associated risks of childhood insulin-dependent diabetes in the Finnish population: I. Allele effects at A, B, and DR loci. DiMe Study Group. Childhood Diabetes in Finland.

Variation in the risk of insulin-dependent diabetes mellitus (IDDM) across alleles at HLA-A, B, and DR loci was investigated in a population-based study of 801 families of children with newly diagnosed IDDM in Finland nationwide. Parallel analyses assessed the relative frequencies of alleles in IDDM children compared with age-matched sibling controls and with the four possible genotypes which could have been inherited from the parents. The joint effects of DR3 and DR4 alleles were investigated under dominant, recessive, and additive models of gene expression. The additive model gave the best fit, though the relative risk for DR4 homozygotes was smaller than predicted. To investigate other alleles, we fitted the standard multiplicative model for alleles at each locus. After controlling for the correlation among alleles, significantly elevated risks were found for B13, DR3, DR4, and DR14. Subjects with these alleles have more than twice the risk of IDDM as those without. Alleles A24 and B62 incurred relative risks between one and two. DR2 and DR5 were significantly negatively associated with IDDM, incurring less than half the risk. These findings support an independent role of class I antigens in the etiology of IDDM.

Adolescent↗
PubMed1995

Variation in HLA-associated risks of childhood insulin-dependent diabetes in the Finnish population: II. Haplotype effects. DiMe Study Group. Childhood Diabetes in Finland.

We fitted models for the main effects of alleles at the HLA-A, B, and DR loci and their haplotypes on the risk of insulin-dependent diabetes mellitus (IDDM). Empirical Bayes methods were used, assuming independent exchangeable normal priors for effects at each locus separately and for haplotype effects. A pure main effects model, pure haplotype effects model, and a combined model were fitted using Gibbs sampling. The main effects model showed that the DR locus had the largest variation in risk between alleles, followed by the B locus; significance tests for each allele in this model were in general agreement with those in the companion paper [Langholz et al. (1995) Genet Epidemiol 12:441-453], although all relative risks were shrunk toward 1.0 in the empirical Bayes analysis. The variance estimate for pure haplotype effects was substantially larger than for any of the three main effects considered in this analysis, but in the combined model, the DR locus showed larger variability than the haplotype deviations. We confirmed that haplotype A2/B56/DR4 previously reported to be common in Finnish diabetics does indeed confer unusually high risk (relative risk = 7.6, P < 0.001), but found this to be only 1.9 times higher than predicted by its component main effects (P = 0.046). All of the other haplotypes could be adequately explained by their main effects. Empirical Bayes methods provide a natural means of dealing with the problems of multiple comparisons, multicolinearity, and sparse data that complicate the analysis of HLA data.

Adolescent↗
PubMed2001

Dementia, cognitive impairment and mortality in persons aged 65 and over living in the community: a systematic review of the literature.

BACKGROUND: No recent attempt has been made to synthesise information on mortality and dementia despite the theoretical and practical interest in the topic. Our objective was to estimate the influence on mortality of cognitive impairment and dementia. METHODS: Data sources were Medline, Embase, personal files and colleagues' records. Studies were considered if they included a majority of persons aged 65 and over at baseline either drawn from a total community sample or drawn from a random sample from the community. Samples from health care facilities were excluded. The search located 68 community studies. Effect sizes were extracted from the studies and if they were not included in the published studies, effect sizes were calculated where possible: this was possible for 23 studies of cognitive impairment and 32 of dementia. No attempt was made to contact authors for missing data. RESULTS: For the studies of cognitive impairment Fisher's method (a vote counting method), gave a p-value (from eight studies) of 0.00001. For studies of dementia, age-adjusted confidence intervals (CI) were pooled (odds ratio (OR) 2.63 with 95% CI 2.17 to 3.21 from six studies). CONCLUSIONS: Levels of cognitive impairment commonly found in community studies give rise to an increased risk of mortality, and this appears to be true even for quite mild levels of impairment. The analysis confirms the increased risk of mortality for dementia, but reveals a dearth of information on the causes of the excess mortality and on possible effect modification by age, dementia subtype or other variables.

Age Distribution↗
PubMed2001

Proportional treatment effects for count response panel data: effects of binary exercise on health care demand.

We define conditional and marginal treatment effects appropriate for count data, and then conduct an empirical analysis for the effects of exercise on health care demand using panel data from the Health Retirement Study. The response variables are office visits to doctors and hospitalization days, and the treatments of interest are light and vigorous exercises. We found that short-run light exercise increases health care demand by 3-5%, whereas long-run light exercise decreases it by 3-6%. We also found that short-run vigorous exercise decreases health care demand by 1-2%, whereas long-run vigorous exercise decreases it by 1-3%. However, many of these numbers are not statistically significantly different from zero. These findings suggest that it will be difficult to reduce health care cost much by encouraging people to do more exercise--at least in the short-run.

Adult↗
PubMed2001

Estimating treatment effects in randomized clinical trials with non-compliance: the impact of maternal smoking on birthweight.

This paper assesses the causal impact of late-term (8th month) maternal smoking on birthweight using data from a randomized clinical trial, in which some women were encouraged not to smoke, while others were not. The estimation of treatment effects in this case is made difficult as a result of the presence of non-compliers, women who would not change their smoking status, regardless of the receipt of encouragement. Because these women are not at risk of changing treatment status, treatment effect distributions may be difficult to construct for them. Consequently, the paper focuses on obtaining the distribution of treatment impacts for the sub-set of compliers found in the data. Because compliance status is not observed for all subjects in the sample, a Bayesian finite mixture model is estimated that recovers the treatment effect parameters of interest. The complier average treatment effect implies that smokers give birth to infants weighing 348 g less than those of non-smokers, on average, although the 95% posterior density interval contains zero. The treatment effect is stronger for women who were moderate smokers prior to pregnancy, implying a birthweight difference of 430 g. However, the model predicts that only about 22% of the women in the sample were at risk of changing their smoking behaviour in response to encouragement to quit.

Bayes Theorem↗