Author Correction: Colonoscopy and fecal immunochemical testing versus usual care in diagnostic colorectal cancer screening: the SCREESCO randomized controlled trial.
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Published Erratum↗
Biomedical subjects
Chris Metcalfe
Publications and source records attributed to Chris Metcalfe.
Colonoscopy and fecal immunochemical testing versus usual care in diagnostic colorectal cancer screening: the SCREESCO randomized controlled trial.
There is a need to quantify the benefits and harms of colorectal cancer (CRC) screening using primary colonoscopy or fecal immunochemical testing (FIT) compared with usual care with no screening. Guidelines recommend screening in individuals aged 50-75 years using colonoscopy or FIT, and many screening programs use one-sample biennial FIT. Here we compare incidence of diagnosed CRCs and gastrointestinal and cardiovascular events between screening and usual care during the diagnostic phase of the SCREESCO trial. A randomized block method (no masking) assigned 278,280 individuals aged 60 years to once-only colonoscopy, 2 rounds of two-stool FIT with a low cutoff (10 μg g-1 feces) or usual care (control group) in a ratio of 1:6 for colonoscopy versus control and 1:2 for FIT versus control. In the analysis, 31,113 individuals were in the primary colonoscopy arm and 60,267 were in the FIT arm, and there were 186,671 primary colonoscopy controls, of whom 120,521 were also controls for comparison with the FIT arm. After a median follow-up of 4.8 years, the incidence rate of CRC was 107.9 in the colonoscopy arm and 99.9 in controls per 100,000 person-years (incidence rate ratio (IRR): 1.08, 95% confidence interval (CI): 0.91-1.28) and 96.0 in the FIT arm and 103.9 in controls (IRR: 0.92, 95% CI: 0.81-1.05). Rates of stage I-II CRC were higher in the colonoscopy arm (IRR: 1.38, 95% CI: 1.09-1.74) and in the FIT arm (IRR: 1.19, 95% CI: 0.99-1.43) versus controls. Rates of cardiovascular and gastrointestinal events were slightly higher in the intervention arms during the first year and were subsequently more similar to controls. Our findings of an increase in CRC detection implies a benefit of screening while the increase in adverse events suggests some initial harm. ClinicalTrials.gov: NCT02078804 .
Humans↗
Insulin-like growth factor-I and growth in height, leg length, and trunk length between ages 5 and 10 years.
OBJECTIVE: IGF-I, a major regulator of childhood growth, is also associated with the risk of several cancers in adult life. Adult height and particularly leg length are also associated with cancer risk. Prepubertal growth is more in leg than trunk length, and it has been suggested that leg length might be a biomarker of childhood IGF-I. However, there is little information on the association between childhood IGF-I and subsequent leg and trunk growth. In this study, we investigated the association of IGF-I measured at 5 and 7-8 yr with growth in height and the components of height (leg and trunk length) from 5 yr to 9-10 yr. PARTICIPANTS: A total of 675 children participated in the Avon Longitudinal Study of Parents and Children. RESULTS: IGF-I was strongly positively associated with growth in height in both sexes. Among boys, IGF-I was strongly associated with subsequent growth in both leg and trunk length, but there was no evidence that IGF-I was more strongly associated with one component of growth than the other. Among girls, IGF-I was strongly positively associated with growth in trunk but not leg length, although there was only weak evidence that these two associations differed in strength (P = 0.058). CONCLUSIONS: These results support the contention that the associations between height and cancer may be mediated by variation in childhood IGF-I. However, they provide no evidence to support the hypothesis that leg length is a better biomarker of childhood IGF-I levels than trunk length.
Anthropometry↗
Satisfaction with care: an independent outcome measure in surgical oncology.
BACKGROUND: Outcomes for treatment for upper gastrointestinal cancer traditionally include procedure-related morbidity and mortality and long-term survival. Patient-reported outcomes, such as quality of life (QOL) and satisfaction measures, add to standard end points, but associations between these factors are not fully understood. This study examined how patient satisfaction related to surgical morbidity, treatment type, and QOL outcomes after inpatient treatment for upper gastrointestinal cancer. METHODS: Consecutive patients who had completed treatment in one unit were invited to participate in this study and complete the European Organization for Research and Treatment of Cancer QLQ-PATSAT32 and QLQ-C30 questionnaires within 2 months of discharge. Regression analyses examined relationships between satisfaction and surgical morbidity (major complications and type of treatment) and between satisfaction and QOL variables, adjusting for age and sex. RESULTS: During the study, 181 patients were treated, 162 were eligible, and 139 returned both questionnaires (response rate, 86%). Of the study sample, the treatment outcome was potential cure in 105 (67 esophagectomy and 38 D2 gastrectomy), and 34 received palliative treatment. Thirty-seven patients (27%) had major complications. Patients who received palliative treatment reported satisfaction and QOL scores similar to those of patients who received curative treatment. However, patients who experienced major morbidity reported significantly worse QOL than those without morbidity (P<.01). Satisfaction scores were the same in patients with or without complications. There were no associations between satisfaction and QOL scores (r<.34). CONCLUSIONS: Patient satisfaction with hospital care is independent of morbidity, treatment type, and QOL outcomes. It may be used to feed back information to providers of health care to improve patients' experiences of treatment.
Adult↗
The importance of varying the event generation process in simulation studies of statistical methods for recurrent events.
Statistical methods for the analysis of recurrent events are often evaluated in simulation studies. A factor rarely varied in such studies is the underlying event generation process. If the relative performance of statistical methods differs across generation processes, then studies based upon one process may mislead. This paper describes the simulation of recurrent events data using four models of the generation process: Poisson, mixed Poisson, autoregressive, and Weibull. For each model four commonly used statistical methods for the analysis of recurrent events (Cox's proportional hazards method, the Andersen-Gill method, negative binomial regression, the Prentice-Williams-Peterson method) were applied to 200 simulated data sets, and the mean estimates, standard errors, and confidence intervals obtained. All methods performed well for the Poisson process. Otherwise, negative binomial regression only performed well for the mixed Poisson process, as did the Andersen-Gill method with a robust estimate of the standard error. The Prentice-Williams-Peterson method performed well only for the autoregressive and Weibull processes. So the relative performance of statistical methods depended upon the model of event generation used to simulate data. In conclusion, it is important that simulation studies of statistical methods for recurrent events include simulated data sets based upon a range of models for event generation.
Computer Simulation↗
New methods presented in statistical journals.
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Methods↗
Developmental effects in Japanese medaka (Oryzias latipes) exposed to nonylphenol ethoxylates and their degradation products.
The endocrine modulating potency of five alkylphenol compounds to fish, including nonylphenol (NP), three nonylphenol ethoxylate mixtures (NP1EO, NP4EO, NP9EO) and one nonylphenol ethoxycarboxylate (NP1EC) was assessed using in vivo tests conducted with Japanese medaka (Oryzias latipes). Medaka exposed to test materials from 1 day to 100 days post-hatch were monitored for alterations to sex ratios and secondary sex characteristics and development of gonadal intersex (i.e., testis-ova). The treatment with 100 microg l-1 NP (measured 29 microg l-1) induced gonadal intersex in over 80% of exposed males, mixed secondary sex characteristics in over 40% of exposed fish and suppression of the development of papillae on the anal fin of 100% of males. The 30 microg l-1 NP (measured 8.7 microg l-1) treatment induced gonadal intersex in only one of the 22 exposed males and mixed secondary sex characteristics in approximately 20% of the exposed fish. An elevated incidence of fish with mixed secondary sex characteristics and suppression of papillae development was also observed in the treatment with NP1EO at the highest test concentration of 300 microg l-1 (measured 105 microg l-1). There was no evidence of mixed secondary sex characteristics or gonadal intersex in treatments with the remaining test mixtures. This study confirms that NP is an estrogenic compound that could affect gonadal development in fish chronically exposed to concentrations in the range of 10 microg l-1. NP1EO is very weakly estrogenic at concentrations that are an order of magnitude higher than the lowest observed effect concentration for nonylphenol.
Animals↗
Release of persistent organic contaminants from carcasses of Lake Ontario Chinook salmon (Oncorhynchus tshawytscha).
About 20,000 Chinook salmon (Oncorhynchus tshawytscha) from Lake Ontario enter the Credit River, Ontario, Canada every fall to spawn and die. In this study, samples of muscle and eggs collected from female Chinook salmon entering the Credit River contained total PCBs, DDT compounds and other organochlorine (OC) compounds at mug/kg concentrations. Semi-permeable membrane devices (SPMDs) were deployed at a reference site above the spawning grounds and at two downstream sites at intervals over a 14-month period that spanned two spawning runs. There was an increase in the concentrations of total PCBs, total DDT and other classes of OCs in the SPMDs deployed at the two downstream sites during and after both spawning runs; indicating that the decay of salmon releases contaminants into the river. Based upon the concentrations of contaminants in the salmon tissues, approximately 75 g of total PCBs and 35 g of total DDT compounds would be transported annually into the Credit River from this source.
Animals↗
Intensive case management for severe psychotic illness: is there a general benefit for patients with complex needs? A secondary analysis of the UK700 trial data.
The UK700 trial failed to demonstrate an overall benefit of intensive case management (ICM) in patients with severe psychotic illness. This does not discount a benefit for particular subgroups, and evidence of a benefit of ICM for patients of borderline intelligence has been presented. The aim of this study is to investigate whether this effect is part of a general benefit for patients with severe psychosis complicated by additional needs. In the UK700 trial patients with severe psychosis were randomly allocated to ICM or standard case management. For each patient group with complex needs the effect of ICM is compared with that in the rest of the study cohort. Outcome measures are days spent in psychiatric hospital and the admission and discharge rates. ICM may be of benefit to patients with severe psychosis complicated by borderline intelligence or depression, but may cause patients using illicit drugs to spend more time in hospital. There was no convincing evidence of an effect of ICM in a further seven patient groups. ICM is not of general benefit to patients with severe psychosis complicated by additional needs. The benefit of ICM for patients with borderline intelligence is an isolated effect which should be interpreted cautiously until further data are available.
Critical Care↗
Cause-specific hospital admission and mortality among working men: association with socioeconomic circumstances in childhood and adult life, and the mediating role of daily stress.
BACKGROUND: The aim of this study was to investigate the association of childhood and adulthood social class with the occurrence of specific diseases, including those not associated with a high mortality rate, and to investigate daily stress as the mechanism for that part of any association which cannot be accounted for by established risk factors. METHODS: This was a prospective cohort study with 25 years of follow-up for cause-specific morbidity and mortality. A total of 5577 Scottish men were recruited from 27 workplaces in the West of Scotland. Childhood social class was determined from the occupation held by the individual's father, and adulthood social class from the individual's occupation at enrolment. Daily stress was measured at enrolment using the Reeder Stress Inventory. RESULTS: Health differentials were found for cardiovascular diseases, lung cancer, peptic ulcer, asthma, accidents and violence, alcohol-related diseases, and perhaps psychiatric illness. Adulthood circumstances were associated with the incidence of most diseases in adulthood, the exception being stroke, which was strongly associated with less privileged circumstances in childhood. Both childhood and adulthood circumstances contributed to the incidence of coronary heart disease. Daily stress did not underlie any of these associations once the influence of established risk factors had been taken into account. CONCLUSIONS: Socioeconomic circumstances in childhood and adulthood both contribute to health differentials in adulthood, the relative contributions depending upon the particular disease. Where known risk factors explained only part of the excess of a disease among individuals raised or living in less-privileged circumstances, there was no evidence to suggest that daily stress was the reason for the unexplained excess.
Activities of Daily Living↗
Analyzing the duration of recurrent events in clinical trials: a comparison of approaches using data from the UK700 trial of psychiatric case management.
In studies of chronic disease the outcome measure may be based upon the duration of recurring illness. Our example is the UK700 trial of psychiatric case management, where the total number of days spent in hospital over a 2-year follow-up was the primary outcome. Investigations of treatment effect modifiers were undertaken using an analysis of that primary outcome, a comparison of length of hospitalizations, and also a multi-state modeling approach. The days in hospital outcome was relatively straightforward to analyze, and allowed the complete randomized treatment groups to be compared. In contrast, the comparison of length of hospitalizations included only hospitalized patients, with censored observations not being well accommodated. The multi-state model provided separate treatment effect estimates for admission and discharge, this being more informative about how any reduction in days spent in hospital is achieved. Estimation of the treatment effects through the use of proportional hazards regression allowed appropriate incorporation of censored observations. However, with the multi-state model approach treatment effect estimates are not based upon comparisons of complete randomized treatment groups, as individuals are removed from the risk set for admission whilst at risk for discharge, and vice versa. We conclude that total duration is an appropriate primary outcome for clinical trials, but that multi-state models deserve greater use as an informative secondary analysis.
Case Management↗
Is subjective social status a more important determinant of health than objective social status? Evidence from a prospective observational study of Scottish men.
Both subjective and objective measures of lower social position have been shown to be associated with poorer health. A psychosocial, as opposed to material, aetiology of health inequalities predicts that subjective social status should be a stronger determinant of health than objective social position. In a workplace based prospective study of 5232 Scottish men recruited in the early 1970s and followed up for 25 years we examined the association between objective and subjective indices of social position, perceived psychological stress, cardiovascular disease risk factors and subsequent health. Lower social position, whether indexed by more objective or more subjective measures, was consistently associated with an adverse profile of established disease risk factors. Perceived stress showed the opposite association. The main subjective social position measure used was based on individual perceptions of workplace status (as well as their actual occupation, men were asked whether they saw themselves as "employees", "foremen", or "managers"). Compared to foremen, employees had a small and imprecisely estimated increased risk of all cause mortality, whereas managers had a more marked decreased risk. The strongest predictors of increased mortality were father's manual as opposed to non-manual occupation; lack of car access and shorter stature, (an indicator of material deprivation in childhood). In the fully adjusted analyses, perceived work-place status was only weakly associated with mortality. In this population it appears that objective material circumstances, particularly in early life, are a more important determinant of health than perceptions of relative status. Conversely, higher perceived stress was not associated with poorer health, presumably because, in this population, higher stress was not associated with material disadvantage. Together these findings suggest that, rather than targeting perceptions of disadvantage and associated negative emotions, interventions to reduce health inequalities should aim to reduce objective material disadvantage, particularly that experienced in early life.
Administrative Personnel↗
Exercise training in patients with chronic heart failure: more information is needed on outcomes in individual studies.
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Chronic Disease↗
Intra- and inter-species differences in persistent organic contaminants in the blubber of blue whales and humpback whales from the Gulf of St. Lawrence, Canada.
Biopsy samples of blubber from adult male and female blue whales, and from female and young-of-the-year humpback whales were collected during the summers of 1992-1999 in the Gulf of St. Lawrence, Canada. In blue whales, concentrations of 25 PCB congeners, DDT and metabolites and several other organochlorine compounds were present at higher concentrations in the blubber of males relative to females; reflecting maternal transfer of these persistent contaminants from females into young. Sex-related differences in concentrations were not observed with less persistent contaminants, such as HCHs. In humpback whale samples, there were no significant differences in the concentrations of PCBs and organochlorine compounds in the blubber of females and calves. These data indicate that calves quickly bioaccumulate contaminants by transplacental and lactational routes to concentrations that are in equilibrium with females. In comparisons between contaminant concentrations and patterns in the blubber of female blue and humpback whales, there were no significant differences in concentrations, but the proportions of some PCB congeners, HCH isomers, and DDT and its metabolites were different in the two baleen whale species. These may reflect differences in the diet of the two species, since fish comprise a large part of the diet of humpback whales and blue whales feed exclusively on euphausiid crustaceans (i.e. krill).
Adipose Tissue↗
Frequent job change and associated health.
The contemporary labour market is widely regarded as having become more "flexible". It is proposed that such flexibility is a characteristic of employment histories which will have effects on psychosocial status, health-related behaviour, and physical health. Recent increases in flexibility are unlikely to have accumulated over sufficient portions of individual employment histories for any effect on health to be apparent, but a "preview" of these effects may be gained from study of older cohorts. This cross-sectional study is based on data collected in the early 1970s from 5399 men and 945 women in paid work, recruited from 27 workplaces in the west of Scotland. A flexible employment history was defined as one encompassing a large number of changes between jobs. Perceived psychological stress, health behaviour (cigarette smoking, alcohol consumption, physical exercise), physiology (diastolic blood pressure, body mass index, forced expiratory volume, plasma cholesterol concentration) and current health (angina, myocardial ischaemia) were assessed. Those individuals who reported having experienced frequent job change were more likely to smoke, consume greater amounts of alcohol, and perhaps to exercise less. Similar findings were observed in both males and females, and for different age and socio-economic groups. We found no suggestion that this association was due to higher levels of psychosocial stress, and the expected consequences for health were not observed. Interpretation of these findings is not straightforward due to an uncertain direction of causation, and a possible selection bias. However, the observed relationship between frequent job changing and a higher incidence of health risk behaviours, in the absence of a relationship with poorer health, invites further research.
Adult↗
Self-reported stress and subsequent hospital admissions as a result of hypertension, varicose veins and haemorrhoids.
BACKGROUND: This study examines a cohort in which individuals of privileged socio-economic position report greater psychological stress. We have previously shown in this cohort that stress is unrelated to coronary heart disease as measured by hospital discharge diagnosis and cause-specific death. In contrast, stress and hospitalization for cardiovascular conditions not requiring mandatory admission were associated. We hypothesized that psychosocial factors, in particular reporting tendency, are the likely mediator of this association, and the present study considers this further. METHODS: A total of 5,596 men underwent a health screening during which they completed the Reeder Stress Inventory. Details of hospital admissions were retrieved from the Scottish Morbidity Records over a 21 year follow-up. Relationships between stress and admission were evaluated using proportional hazards regression. RESULTS: Compared with low stress, reported high stress was found to be associated with increased numbers of admissions for each of three most common cardiovascular causes of non-mandatory admission: adjusted hazard ratios were 3.43 for essential hypertension (95 per cent confidence interval (CI) 1.36-8.65), 1.91 for lower limb varicose veins (95 per cent CI 1.12-3.24), and 2.01 for haemorrhoids (95 per cent CI 1.16-3.51). Stress and blood pressure at baseline were not associated. CONCLUSION: The association between stress and admissions as a result of hypertension appears unlikely to be mediated by blood pressure. More likely is a mechanism based upon the reporting of symptoms, or the recording of discharge diagnoses. There is no obvious medical explanation for associations between stress and hospitalization as a result of varicose veins or haemorrhoids, and again it is likely that psychosocial factors provide the mechanism.
Adult↗
A contemporary validation of the Reeder Stress Inventory.
OBJECTIVES: To examine the construct validity of the RSI in a contemporary cohort. DESIGN: A cross-sectional investigation of 1,717 employed individuals who responded to the second stage of a study of occupational stress. METHODS: Scores on the RSI are compared to smoking and drinking habits, social class, and two measures of health (number of days sick leave, and number of visits to a GP during the previous year). The RSI was compared to three questionnaires measuring concepts related to stress: the 12-item General Health Questionnaire (GHQ-12), the Hospital Anxiety and Depression Scale (HADS), and the Karasek Job Strain Questionnaire. RESULTS: Higher levels of stress, as measured by the RSI, were associated with smoking a greater number of cigarettes, and, if the respondent drank alcohol, greater consumption of alcoholic drinks. High levels of stress were also associated with having taken more days sick leave, having made more frequent visits to a GP, and, somewhat unexpectedly, with being a teetotaller, and with holding a non-manual occupation. Of the questionnaire measures, the strongest association was between the RSI and HADS anxiety subscale, consistent with an overlap between the concepts of stress and anxiety. CONCLUSIONS: This study supports the construct validity of the RSI in a sample of employed individuals.
Adult↗
Gonadal differentiation in frogs exposed to estrogenic and antiestrogenic compounds.
Exposure of amphibians to endocrine disrupting compounds (EDCs) may alter differentiation of gonads, especially when exposures begin during early life stages. Gonadal differentiation was observed in leopard frogs (Rana pipiens) and wood frogs (Rana sylvatica) exposed as tadpoles to estrogenic (estradiol, ethinylestradiol, nonylphenol) and antiestrogenic compounds (an aromatase inhibitor, flavone, and an antiestrogen, ICI 182780). Exposure to all compounds at micrograms/L concentrations altered gonadal differentiation in some animals by inducing either complete feminization or an intersex condition, and altered testicular tubule morphology, increased germ cell maturation (vitellogenesis), and oocyte atresia. Comparisons between the two species indicate that R. pipiens are more susceptible to sex reversal and development of intersex gonads. However, R. sylvatica also showed alterations to testicular morphology, germ cell maturation, and ooctye atresia. These laboratory results indicate that amphibians could be susceptible to altered gonadal differentiation and development when exposed to estrogenic and antiestrogenic compounds in aquatic environments, such as those impacted by agricultural, industrial, and municipal runoff.
Animals↗