Christoph E. Minder

Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis

BACKGROUND Insulin-like growth factor (IGF)-I and its main binding protein, IGFBP-3, modulate cell growth and survival, and are thought to be important in tumour development. Circulating concentrations of IGF-I might be associated with an increased risk of cancer, whereas IGFBP-3 concentrations could be associated with a decreased cancer risk. METHODS We did a systematic review and meta-regression analysis of case-control studies, including studies nested in cohorts, of the association between concentrations of IGF-I and IGFBP-3 and prostate, colorectal, premenopausal and postmenopausal breast, and lung cancer. Study-specific dose-response slopes were obtained by relating the natural log of odds ratios for different exposure levels to blood concentrations normalised to a percentile scale. FINDINGS We identified 21 eligible studies (26 datasets), which included 3609 cases and 7137 controls. High concentrations of IGF-I were associated with an increased risk of prostate cancer (odds ratio comparing 75th with 25th percentile 1.49, 95% CI 1.14-1.95) and premenopausal breast cancer (1.65, 1.26-2.08) and high concentrations of IGFBP-3 were associated with increased risk of premenopausal breast cancer (1.51, 1.01-2.27). Associations were larger in assessments of plasma samples than in serum samples, and in standard case-control studies compared with nested studies. INTERPRETATION Circulating concentrations of IGF-I and IGFBP-3 are associated with an increased risk of common cancers, but associations are modest and vary between sites. Although laboratory methods need to be standardised, these epidemiological observations could have major implications for assessment of risk and prevention of cancer.

Educational inequalities in cause-specific mortality in middle-aged and older men and women in eight western European populations

BACKGROUND Studies of socioeconomic disparities in patterns of cause of death have been limited to single countries, middle-aged people, men, or broad cause of death groups. We assessed contribution of specific causes of death to disparities in mortality between groups with different levels of education, in men and women, middle-aged and old, in eight western European populations. METHODS We analysed data from longitudinal mortality studies by cause of death, between Jan 1, 1990, and Dec 31, 1997. Data were included for more than 1 million deaths in 51 million person years of observation. FINDINGS Absolute educational inequalities in total mortality peaked at 2127 deaths per 100000 person years in men, and at 1588 deaths per 100000 person years in women aged 75 years and older. In this age-group, rate ratios were greater than 1.00 for total mortality and all specific causes of death, apart form prostate cancer in men and lung cancer in women, showing increased mortality in low versus high educational groups. In men, cardiovascular diseases accounted for 39% of the difference between low and high educational groups in total mortality, cancer for 24%, other diseases for 32%, and external causes for 5%. Among women, contributions were 60%, 11%, 30%, and 0%, respectively. The contributions of cerebrovascular disease, other cardiovascular diseases, pneumonia, and COPD strongly increased by age, whereas those of cancer and external causes declined. Although relative inequalities in total mortality were closely similar in all populations, we noted striking differences in the contribution of specific causes to these inequalities. INTERPRETATION Research needs to be broadened to include older populations, other diseases, and populations from different parts of Europe. Effective interventions should be developed and implemented to reduce exposure to cardiovascular risk factors in low-educational groups.

On the epidemiology of running injuries The 1984 Bern Grand-Prix study

Using a survey questionnaire design, we investigated the incidence, site, and nature of jogging injuries among all participants of a popular 16 km race. The response rate was 83.6%. Of 4,358 male joggers, 45.8% had sustained jogging injuries during the 1 year study period, 14.2% had required medical care, and 2.3% had missed work because of jogging injuries. Occur rence of jogging injuries was independently associated with higher weekly mileage (P < 0.001), history of previous running injuries (P < 0.001), and competitive training motivation (P = 0.03). Higher mileage was also associated with more frequent medical consultations due entirely to jogging-related injuries. In 33 to 44 year olds (N = 1,757), the number of years of running was inversely related to incidence of injuries (P = 0.02). Injuries were not significantly related to race running speed, training surface, characteristics of running shoes, or relative weight. Achillodynia and calf muscle symptoms were the two most common overuse injuries and occurred significantly more often among older run ners with increased weekly mileage. We conclude that jogging injuries are frequent, that the number of firmly established etiologic factors is low, and that, in recom mending jogging, moderation should be the watchword.

Socioeconomic inequalities in mortality among elderly people in 11 European populations

Study objective: To describe mortality inequalities related to education and housing tenure in 11 European populations and to describe the age pattern of relative and absolute socioeconomic inequalities in mortality in the elderly European population. Design and Methods: Data from mortality registries linked with population census data of 11 countries and regions of Europe were acquired for the beginning of the 1990s. Indicators of socioeconomic status were educational level and housing tenure. The study determined mortality rate ratios, relative indices of inequality (RII), and mortality rate differences. The age range was 30 to 90+ years. Analyses were performed on the pooled European data, including all populations, and on the data of populations separately. Data were included from Finland, Norway, Denmark, England and Wales, Belgium, France, Austria, Switzerland, Barcelona, Madrid, and Turin. Main results: In Europe (populations pooled) relative inequalities in mortality decreased with increasing age, but persisted. Absolute educational mortality differences increased until the ages 90+. In some of the populations, relative inequalities among older women were as large as those among middle aged women. The decline of relative educational inequalities was largest in Norway (men and women) and Austria (men). Relative educational inequalities did not decrease, or hardly decreased with age in England and Wales (men), Belgium, Switzerland, Austria, and Turin (women). Conclusions: Socioeconomic inequalities in mortality among older men and women were found to persist in each country, sometimes of similar magnitude as those among the middle aged. Mortality inequalities among older populations are an important public health problem in Europe.

Effects of exposure to 16.7 Hz magnetic fields on urinary 6-hydroxymelatonin sulfate excretion of Swiss railway workers

Abstract: The aim of our study was to examine the effects of 16.7 Hz electromagnetic‐field exposure on pineal melatonin production in healthy humans. The study was based on comparing urinary 6‐hydroxymelatonin sulfate (6‐OHMS) levels of 108 male railway workers between leisure periods and days following the start of service on electrically powered engines (66 engineers) or working beneath transmission lines (42 railway employees such as train attendants and station managers; controls). A repeated measures design was used, i.e., each volunteer served as his own control. The exposure averaged 20 μTesla in the most exposed workers and around 1 μTesla in the least exposed. Apart from magnetic exposure the workers were subject to a shift work schedule with daily advances between 15 min and 1 hr. Melatonin was assessed by sampling urinary 6‐OHMS both in the morning and the early evening.

Ruling a diagnosis in or out with “SpPIn” and “SnNOut”: a note of caution

Dr X is back from her annual leave. Dr Y, the locum doctor, reports on the patients he saw during her absence, including a 40 year old teacher who had sprained her right ankle. Returning from a conference, she had stumbled while walking down the stairs with a heavy bag. Examination revealed a moderately swollen lateral right ankle. The patient was able to walk but was clearly in pain. Her breath smelt of alcohol. Dr Y had applied the Ottawa ankle rules—decision rules designed to exclude fractures of the malleolus and the midfoot—and found no bone tenderness.1 He had previously visited the website of a centre for evidence based medicine2 and printed out a list of diagnostic tests that can rule out, or rule in, the condition in question without requiring further investigations. The probability of disease, given a positive or negative test result (post-test probability), is usually obtained by calculating the likelihood ratio of the test result and using formulas based on Bayess theorem (see box 1), or a nomogram,3 to convert the estimated probability of the suspected diagnosis before the test result was known (pretest probability) into a post-test probability, which takes the result into account.4 Likelihood ratios indicate how many times more likely a test result is to be expected in a patient with the disease compared with a person free of the disease and thus measure a tests ability to modify pretest probabilities. David Sackett and others have argued that such calculations are unnecessary when a test is highly sensitive or highly specific.4–6 In this situation the likelihood ratio of a negative test will generally be very small, and the likelihood ratio of a positive test very large. A negative test will thus rule out, and a positive result …

Adverse Event Assessment of Antimuscarinics for Treating Overactive Bladder: A Network Meta-Analytic Approach

Background Overactive bladder (OAB) affects the lives of millions of people worldwide and antimuscarinics are the pharmacological treatment of choice. Meta-analyses of all currently used antimuscarinics for treating OAB found similar efficacy, making the choice dependent on their adverse event profiles. However, conventional meta-analyses often fail to quantify and compare adverse events across different drugs, dosages, formulations, and routes of administration. In addition, the assessment of the broad variety of adverse events is dissatisfying. Our aim was to compare adverse events of antimuscarinics using a network meta-analytic approach that overcomes shortcomings of conventional analyses. Methods Cochrane Incontinence Group Specialized Trials Register, previous systematic reviews, conference abstracts, book chapters, and reference lists of relevant articles were searched. Eligible studies included randomized controlled trials comparing at least one antimuscarinic for treating OAB with placebo or with another antimuscarinic, and adverse events as outcome measures. Two authors independently extracted data. A network meta-analytic approach was applied allowing for joint assessment of all adverse events of all currently used antimuscarinics while fully maintaining randomization. Results 69 trials enrolling 26′229 patients were included. Similar overall adverse event profiles were found for darifenacin, fesoterodine, transdermal oxybutynin, propiverine, solifenacin, tolterodine, and trospium chloride but not for oxybutynin orally administered when currently used starting dosages were compared. Conclusions The proposed generally applicable transparent network meta-analytic approach summarizes adverse events in an easy to grasp way allowing straightforward benchmarking of antimuscarinics for treating OAB in clinical practice. Most currently used antimuscarinics seem to be equivalent first choice drugs to start the treatment of OAB except for oral oxybutynin dosages of ≥10 mg/d which may have more unfavorable adverse event profiles.

Education level inequalities and transportation injury mortality in the middle aged and elderly in European settings

Objective: To study the differential distribution of transportation injury mortality by educational level in nine European settings, among people older than 30 years, during the 1990s. Methods: Deaths of men and women older than 30 years from transportation injuries were studied. Rate differences and rate ratios (RR) between high and low educational level rates were obtained. Results: Among men, those of low educational level had higher death rates in all settings, a pattern that was maintained in the different settings; no inequalities were found among women. Among men, in all the settings, the RR was higher in the 30–49 age group (RR 1.46, 95% CI 1.32 to 1.61) than in the age groups 50–69 and ⩾70 years, a pattern that was maintained in the different settings. For women for all the settings together, no differences were found among educational levels in the three age groups. In the different settings, only three had a high RR in the youngest age group, Finland (RR 1.33, 95% CI 1.01 to 1.74), Belgium (RR 1.38; 95% CI 1.13 to 1.67), and Austria (RR 1.49, 95% CI 0.75 to 2.96). Conclusion: This study provides new evidence on the importance of socioeconomic inequalities in transportation injury mortality across Europe. This applies to men, but not to women. Greater attention should be placed on opportunities to select intervention strategies tailored to tackle socioeconomic inequalities in transportation injuries.

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.

A Randomized Trial of Effects of Health Risk Appraisal Combined With Group Sessions or Home Visits on Preventive Behaviors in Older Adults

BACKGROUND To explore effects of a health risk appraisal for older people (HRA-O) program with reinforcement, we conducted a randomized controlled trial in 21 general practices in Hamburg, Germany. METHODS Overall, 2,580 older patients of 14 general practitioners trained in reinforcing recommendations related to HRA-O-identified risk factors were randomized into intervention (n = 878) and control (n = 1,702) groups. Patients (n = 746) of seven additional matched general practitioners who did not receive this training served as a comparison group. Patients allocated to the intervention group, and their general practitioners, received computer-tailored written recommendations, and patients were offered the choice between interdisciplinary group sessions (geriatrician, physiotherapist, social worker, and nutritionist) and home visits (nurse). RESULTS Among the intervention group, 580 (66%) persons made use of personal reinforcement (group sessions: 503 [87%], home visits: 77 [13%]). At 1-year follow-up, persons in the intervention group had higher use of preventive services (eg, influenza vaccinations, adjusted odds ratio 1.7; 95% confidence interval 1.4-2.1) and more favorable health behavior (eg, high fruit/fiber intake, odds ratio 2.0; 95% confidence interval 1.6-2.6), as compared with controls. Comparisons between intervention and comparison group data revealed similar effects, suggesting that physician training alone had no effect. Subgroup analyses indicated favorable effects for HRA-O with personal reinforcement, but not for HRA-O without reinforcement. CONCLUSIONS HRA-O combined with physician training and personal reinforcement had favorable effects on preventive care use and health behavior.