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Biomedical subjects

Til Stürmer

Publications and source records attributed to Til Stürmer.

At least 19 recordsLinked to original sources
PubMed2006

Personality, lifestyle, and risk of cardiovascular disease and cancer: follow-up of population based cohort.

OBJECTIVE: To study the relation between measures of personality and risk of cardiovascular disease and cancer in a large cohort. DESIGN: Follow-up of population based cohort. SETTING: Heidelberg, Germany. PARTICIPANTS: 5114 women and men aged 40-65 in 1992-5. MAIN OUTCOME MEASURES: Psychological traits assessed by several standardised personality questionnaires in 1992-5, related to cause of death (to 2002-3) or reported incidence of cardiovascular diseases and cancer (validated by treating doctors). Relative risks (and 95% confidence intervals) for combined morbidity and mortality according to five important personality traits were estimated using multivariable Cox proportional hazards models. RESULTS: During median follow-up of 8.5 years, 257 participants died and 72 were diagnosed with a heart attack, 62 with stroke, and 240 with cancer (morbidity and mortality combined). A high internal locus of control over disease was associated with a decreased risk of myocardial infarction (adjusted relative risk for an increase of 1 SD = 0.75; 95% confidence interval 0.58 to 0.96). An increase of 1 SD in time urgency was associated with a decreased risk of cancer (adjusted relative risk 0.83; 0.73 to 0.95). Other major personality traits--anger control, psychoticism, and symptoms of depression--were not consistently associated with myocardial infarction, stroke, or cancer. CONCLUSION: Internal locus of control over disease and time urgency seem to be associated with reduced risk for common chronic diseases, probably by affecting unmeasured health related behaviour. The other personality traits assessed had no major impact on cardiovascular disease and cancer.

Adult↗
PubMed2006

Variable selection for propensity score models.

Despite the growing popularity of propensity score (PS) methods in epidemiology, relatively little has been written in the epidemiologic literature about the problem of variable selection for PS models. The authors present the results of two simulation studies designed to help epidemiologists gain insight into the variable selection problem in a PS analysis. The simulation studies illustrate how the choice of variables that are included in a PS model can affect the bias, variance, and mean squared error of an estimated exposure effect. The results suggest that variables that are unrelated to the exposure but related to the outcome should always be included in a PS model. The inclusion of these variables will decrease the variance of an estimated exposure effect without increasing bias. In contrast, including variables that are related to the exposure but not to the outcome will increase the variance of the estimated exposure effect without decreasing bias. In very small studies, the inclusion of variables that are strongly related to the exposure but only weakly related to the outcome can be detrimental to an estimate in a mean squared error sense. The addition of these variables removes only a small amount of bias but can increase the variance of the estimated exposure effect. These simulation studies and other analytical results suggest that standard model-building tools designed to create good predictive models of the exposure will not always lead to optimal PS models, particularly in small studies.

Confounding Factors, Epidemiologic↗
PubMed2006

Prescription opioid use among older adults with arthritis or low back pain.

OBJECTIVE: To examine patterns of chronic opioid use in selected groups with arthritis and low back pain and compare them with patterns among persons with ischemic heart disease. METHODS: The study database consisted of Medicare beneficiaries who were enrolled in a drug benefit program for low-to-moderate income Pennsylvania residents. We identified selected patients who had a diagnosis of rheumatoid arthritis, osteoarthritis, chronic low back pain, or ischemic heart disease since 1995. Chronic opioid use, defined as at least six 30-day prescriptions in a year, was the endpoint of interest. We examined the proportion of patients meeting this definition during the period 1996-2001 and determined predictors based on multivariable Cox proportional hazards models. RESULTS: Four percent of subjects with rheumatoid arthritis used opioids chronically in 2001, compared with <1% in each of the other groups. There was no increase in the chronic use of opioids over the 6-year study period. Low-potency opioids were the most commonly prescribed preparations for chronic users from all patient groups. The prior use of medicines for psychiatric illness, including benzodiazepines or barbiturates, was associated with chronic prescription opioid use across all diagnoses. However, subjects with a prior diagnosis of psychiatric illness were less likely to receive chronic opioids. CONCLUSION: Chronic opioid use is relatively uncommon, even among older individuals with arthritis or low back pain. The proportion of these individuals receiving such medicines has not increased in the late 1990s. There seems to be a complex relationship between psychiatric medication use, psychiatric diagnoses, and the use of chronic opioids among these individuals.

Aged↗
PubMed2006

The course of high-sensitive C-reactive protein in correlation with pain and clinical function in patients with acute lumbosciatic pain and chronic low back pain - a 6 months prospective longitudinal study.

In this prospective longitudinal study with a follow-up of 6 months, the course of serum concentration of C-reactive protein was measured by an ultrasensitive immunoassay in 31 patients with acute lumbosciatic pain and 41 patients with chronic low back pain. High-sensitive CRP (hsCRP), pain and clinical function were assessed at ten fixed time-points during follow-up. The course of hsCRP values was assessed in relation to the course of pain and clinical function adjusting for possible confounding factors. At the beginning of the study, there were no statistically significant differences in mean hsCRP levels in patients with acute lumbosciatic pain (1.49mg/l) compared to the levels obtained in patients with chronic low back pain (1.30mg/l) and those in a control group from the general population (1.26mg/l). In patients with acute lumbosciatic pain, hsCRP declined significantly in the initial period of 3 weeks with a corresponding decrease in pain and improvement in function and clinical evaluation as assessed with the straight leg raising test (SLR), whereas after this period, the course of the hsCRP did not correspond with the clinical parameters. In patients with chronic low back pain, hsCRP remained approximately constant throughout the whole period with no correlation with pain or function. As a conclusion, according to this study levels of hsCRP do not have a major clinical relevance when evaluating the long-term course of patients with acute lumbosciatic pain and chronic low back pain and therefore should not be taken into primary consideration when decisions on therapy are made.

Acute Disease↗
PubMed2006

Cardiovascular outcomes in new users of coxibs and nonsteroidal antiinflammatory drugs: high-risk subgroups and time course of risk.

OBJECTIVE: Controversy persists regarding the cardiovascular risks of treatment with selective cyclooxygenase 2 inhibitors (coxibs) and nonselective nonsteroidal antiinflammatory drugs (NSAIDs). This study was undertaken to examine, in a large group of new users of coxibs and NSAIDs, the rate of cardiovascular events, their time course, and whether baseline cardiovascular risk modified the rate ratios (RRs) for future events. METHODS: This cohort study included Medicare beneficiaries who enrolled in a state-run prescription drug plan that fully covered NSAIDs and coxibs without restriction. All study patients started use of a coxib or NSAID after January 1, 1999. The primary composite end point was a hospital admission for either myocardial infarction or ischemic stroke. Predefined exposure groups included the 3 coxibs available in the US during the study period (celecoxib, rofecoxib, and valdecoxib), as well as oral formulations of diclofenac, ibuprofen, naproxen, and a composite of all other NSAIDs. We compared the rate of cardiovascular events associated with each of these agents with that in a reference group of patients who did not use NSAIDs or coxibs, but started other medications unrelated to cardiovascular risk. Daily exposure to all study drugs was assessed based on filled prescription data. A Cox proportional hazards model stratified on calendar year that included other baseline cardiovascular risk factors constituted the primary analysis. RESULTS: We identified 74,838 users of NSAIDs or coxibs, and 23,532 comparable users of other drugs comprised the reference group. Adjusted models demonstrated a significant elevation in the event rate for rofecoxib (RR 1.15, 95% confidence interval [95% CI] 1.06-1.25) and a significant reduction in the rate for naproxen (RR 0.75, 95% CI 0.62-0.92). No other coxib or NSAID was associated with a significant increase or decrease in cardiovascular event rate. The increased rate associated with rofecoxib was seen in the first 60 days of use (adjusted RR 1.14, 95% CI 1.01-1.29) and thereafter (adjusted RR 1.14, 95% CI 1.02-1.28). Kaplan-Meier event curves showed a similar pattern of risk (early and persistent separation of the event curves) among long-term rofecoxib users at low or high baseline cardiovascular risk. CONCLUSION: We found an increased cardiovascular event rate among users of rofecoxib, and a decreased rate with naproxen use. Other coxibs and NSAIDs did not appear to be associated with a difference in event rate compared with users of other drugs. The increase in rate associated with rofecoxib was seen within the first 60 days and persisted. There was no important modification of the event rate based on the patient's baseline cardiovascular risk.

Aged↗
PubMed2006

Insights into different results from different causal contrasts in the presence of effect-measure modification.

PURPOSE: Both propensity score (PS) matching and inverse probability of treatment weighting (IPTW) allow causal contrasts, albeit different ones. In the presence of effect-measure modification, different analytic approaches produce different summary estimates. METHODS: We present a spreadsheet example that assumes a dichotomous exposure, covariate, and outcome. The covariate can be a confounder or not and a modifier of the relative risk (RR) or not. Based on expected cell counts, we calculate RR estimates using five summary estimators: Mantel-Haenszel (MH), maximum likelihood (ML), the standardized mortality ratio (SMR), PS matching, and a common implementation of IPTW. RESULTS: Without effect-measure modification, all approaches produce identical results. In the presence of effect-measure modification and regardless of the presence of confounding, results from the SMR and PS are identical, but IPTW can produce strikingly different results (e.g., RR = 0.83 vs. RR = 1.50). In such settings, MH and ML do not estimate a population parameter and results for those measures fall between PS and IPTW. CONCLUSIONS: Discrepancies between PS and IPTW reflect different weighting of stratum-specific effect estimates. SMR and PS matching assign weights according to the distribution of the effect-measure modifier in the exposed subpopulation, whereas IPTW assigns weights according to the distribution of the entire study population. In pharmacoepidemiology, contraindications to treatment that also modify the effect might be prevalent in the population, but would be rare among the exposed. In such settings, estimating the effect of exposure in the exposed rather than the whole population is preferable.

Bias↗
PubMed2006

Colorectal cancer after start of nonsteroidal anti-inflammatory drug use.

PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, have been consistently shown to reduce the risk of colorectal cancer (CRC) in non-experimental studies, but little is known of the factors associated with starting and continuing regular NSAID use and their effect on the NSAID and CRC association. SUBJECTS AND METHODS: We performed a prospective cohort study of 22,071 healthy male physicians aged 40 to 84 years without indications or contraindications to regular NSAID use at baseline. Annual questionnaires assessed quantity of NSAID use, occurrence of cancer, and risk factors for CRC. Propensity for regular NSAID use (>60 days/year) was estimated using generalized estimating equations. We used a time-varying Cox proportional hazards model to estimate the association between duration since initiation of regular NSAID use and risk for CRC. RESULTS: Regular non-aspirin and any NSAID use increased from 0% to 12% and 1% to 56% over time, respectively and was predicted by age, body mass index, alcohol consumption, medication use, coronary artery disease, gastrointestinal diseases, arthritis, hypertension, and headaches. Over a median follow-up of 18 years, 495 physicians were diagnosed with CRC. There was no trend of CRC risk with increased duration of regular NSAID use. Five or more years of regular use of any NSAID were associated with a relative risk for CRC of 1.0 (95% confidence interval: 0.7-1.5), after adjustment for predictors of regular NSAID use. CONCLUSION: Regular NSAID use was not associated with a substantial risk reduction of CRC after controlling for time-varying predictors of both NSAID use and CRC.

Adult↗
PubMed2006

Indications for propensity scores and review of their use in pharmacoepidemiology.

Use of propensity scores to identify and control for confounding in observational studies that relate medications to outcomes has increased substantially in recent years. However, it remains unclear whether, and if so when, use of propensity scores provides estimates of drug effects that are less biased than those obtained from conventional multivariate models. In the great majority of published studies that have used both approaches, estimated effects from propensity score and regression methods have been similar. Simulation studies further suggest comparable performance of the two approaches in many settings. We discuss five reasons that favour use of propensity scores: the value of focus on indications for drug use; optimal matching strategies from alternative designs; improved control of confounding with scarce outcomes; ability to identify interactions between propensity of treatment and drug effects on outcomes; and correction for unobserved confounders via propensity score calibration. We describe alternative approaches to estimate and implement propensity scores and the limitations of the C-statistic for evaluation. Use of propensity scores will not correct biases from unmeasured confounders, but can aid in understanding determinants of drug use and lead to improved estimates of drug effects in some settings.

Bias↗
PubMed2006

Metabolic abnormalities and risk for colorectal cancer in the physicians' health study.

BACKGROUND: Obesity and diabetes are established risk factors for colorectal cancer but have mainly been assessed independently. There are few data about whether the metabolic syndrome, which refers to a clustering of cardiovascular disease risk factors thought to be related to insulin resistance, including obesity, type 2 diabetes, hyperlipidemia, and hypertension, is associated with colorectal cancer risk. METHODS: During and after the randomized trial of aspirin and beta-carotene, 22,071 healthy male physicians, initially ages 40 to 84 years, reported overweight (body mass index, >or=27 kg/m2), diabetes, elevated blood pressure (>or=130/85 mmHg or use of antihypertensive medication), hypercholesterolemia (>or=240 mg/dL or use of lipid-lowering medication), and occurrence of cancer on annual questionnaires. Adjusted relative risks (RR) and 95% confidence intervals (95% CI) for time-varying metabolic abnormalities and colorectal cancer were estimated using a multivariable proportional hazards model. RESULTS: During 369,966 person-years of follow-up (median, 19 years), 494 physicians developed colorectal cancer. With aging of the cohort, the prevalence of having two or more abnormalities increased from 13% to 35%. Overweight (RR, 1.4; 95% CI, 1.1-1.7) and diabetes (RR, 1.5; 95% CI, 1.1-2.0) were associated with increased risk for colorectal cancer, whereas elevated blood pressure (RR, 1.1; 95% CI, 0.9-1.3) and hypercholesterolemia (RR, 0.9; 95% CI, 0.7-1.1) were not. This model assessing metabolic abnormalities independently was more predictive for colorectal cancer than a model based on the number of abnormalities (each additional abnormality RR, 1.16; 95% CI, 1.05-1.29). CONCLUSIONS: Out of the markers of the metabolic syndrome assessed, overweight and diabetes are risk factors for colorectal cancer, whereas, in contrast to their role in cardiovascular disease, elevated blood pressure and hypercholesterolemia are not.

Adult↗
PubMed2005

A review of the application of propensity score methods yielded increasing use, advantages in specific settings, but not substantially different estimates compared with conventional multivariable methods.

OBJECTIVE: Propensity score (PS) analyses attempt to control for confounding in nonexperimental studies by adjusting for the likelihood that a given patient is exposed. Such analyses have been proposed to address confounding by indication, but there is little empirical evidence that they achieve better control than conventional multivariate outcome modeling. STUDY DESIGN AND METHODS: Using PubMed and Science Citation Index, we assessed the use of propensity scores over time and critically evaluated studies published through 2003. RESULTS: Use of propensity scores increased from a total of 8 reports before 1998 to 71 in 2003. Most of the 177 published studies abstracted assessed medications (N=60) or surgical interventions (N=51), mainly in cardiology and cardiac surgery (N=90). Whether PS methods or conventional outcome models were used to control for confounding had little effect on results in those studies in which such comparison was possible. Only 9 of 69 studies (13%) had an effect estimate that differed by more than 20% from that obtained with a conventional outcome model in all PS analyses presented. CONCLUSIONS: Publication of results based on propensity score methods has increased dramatically, but there is little evidence that these methods yield substantially different estimates compared with conventional multivariable methods.

Bias↗
PubMed2005

Analgesic use and risk of subsequent hypertension in apparently healthy men.

BACKGROUND: Prospective studies have suggested that women who self-select for use of analgesics have an increased risk of hypertension, but data in men are sparse. We tested whether apparently healthy male physicians who reported analgesic use had an increased risk of subsequent hypertension. METHODS: Prospective cohort study of 8229 participants in the Physicians' Health Study who were free of hypertension and completed detailed analgesic questionnaires. Hypertension was defined as self-reported blood pressure of 140/90 mm Hg or higher or use of antihypertensive medication. RESULTS: After a mean of 5.8 years' follow-up, 2234 men (27.2%) reported subsequent hypertension. We categorized the cumulative analgesic use in quintiles. After adjusting for potential confounders, men in the highest quintile had no statistically significant increased risk of hypertension (hazard ratio, 1.12; 95% confidence interval, 0.97-1.31) when compared with those in the lowest quintile. In subgroup analyses, we evaluated the cumulative use of nonsteroidal anti-inflammatory drugs, acetaminophen, and aspirin. Compared with never users, men who reported consuming at least 2500 pills had hazard ratios of 1.05 (95% confidence interval, 0.89-1.24) for nonsteroidal anti-inflammatory drugs, 1.08 (95% confidence interval, 0.87-1.34) for acetaminophen, and 1.16 (95% confidence interval, 0.92-1.48) for aspirin. The results were similar for analgesic use in the year preceding the analgesic questionnaire. CONCLUSION: In this large cohort, apparently healthy male physicians who self-selected for analgesic use had no significantly increased risk of subsequent hypertension, although a small to moderately increased risk cannot be excluded in observational studies.

Acetaminophen↗
PubMed2005

Adjusting effect estimates for unmeasured confounding with validation data using propensity score calibration.

Often, data on important confounders are not available in cohort studies. Sensitivity analyses based on the relation of single, but not multiple, unmeasured confounders with an exposure of interest in a separate validation study have been proposed. In this paper, the authors controlled for measured confounding in the main cohort using propensity scores (PS's) and addressed unmeasured confounding by estimating two additional PS's in a validation study. The "error-prone" PS exclusively used information available in the main cohort. The "gold standard" PS additionally included data on covariates available only in the validation study. Based on these two PS's in the validation study, regression calibration was applied to adjust regression coefficients. This propensity score calibration (PSC) adjusts for unmeasured confounding in cohort studies with validation data under certain, usually untestable, assumptions. The authors used PSC to assess the relation between nonsteroidal antiinflammatory drugs (NSAIDs) and 1-year mortality in a large cohort of elderly persons. "Traditional" adjustment resulted in a hazard ratio for NSAID users of 0.80 (95% confidence interval (CI): 0.77, 0.83) as compared with an unadjusted hazard ratio of 0.68 (95% CI: 0.66, 0.71). Application of PSC resulted in a more plausible hazard ratio of 1.06 (95% CI: 1.00, 1.12). Until the validity and limitations of PSC have been assessed in different settings, the method should be seen as a sensitivity analysis.

Aged↗
PubMed2005

Analytic strategies to adjust confounding using exposure propensity scores and disease risk scores: nonsteroidal antiinflammatory drugs and short-term mortality in the elderly.

Little is known about optimal application and behavior of exposure propensity scores (EPS) in small studies. In a cohort of 103,133 elderly Medicaid beneficiaries in New Jersey, the effect of nonsteroidal antiinflammatory drug use on 1-year all-cause mortality was assessed (1995-1997) based on the assumption that there is no protective effect and that the preponderance of any observed effect would be confounded. To study the comparative behavior of EPS, disease risk scores, and "conventional" disease models, the authors randomly resampled 1,000 subcohorts of 10,000, 1,000, and 500 persons. The number of variables was limited in disease models, but not EPS and disease risk scores. Estimated EPS were used to adjust for confounding by matching, inverse probability of treatment weighting, stratification, and modeling. The crude rate ratio of death was 0.68 for users of nonsteroidal antiinflammatory drugs. "Conventional" adjustment resulted in a rate ratio of 0.80 (95% confidence interval: 0.77, 0.84). The rate ratio closest to 1 (0.85) was achieved by inverse probability of treatment weighting (95% confidence interval: 0.82, 0.88). With decreasing study size, estimates remained further from the null value, which was most pronounced for inverse probability of treatment weighting (n = 500: rate ratio = 0.72, 95% confidence interval: 0.26, 1.68). In this setting, analytic strategies using EPS or disease risk scores were not generally superior to "conventional" models. Various ways to use EPS and disease risk scores behaved differently with smaller study size.

Aged↗
PubMed2004

Prevalence and determinants of antibiotic resistance in faecal Escherichia coli among unselected patients attending general practitioners in Southwest Germany.

PURPOSE: Widespread use of antibiotics is thought to be the main reason for the world-wide increase in antibiotic resistance. Although a great majority of antibiotics are prescribed outside hospitals, little is known about the prevalence and determinants of antibiotic resistance in the general population. METHODS: Escherichia coli (E. coli) was cultured from and minimal inhibitory concentrations against six commonly prescribed antibiotic substances were tested in 750 stool samples of 484 unselected, consecutive outpatients aged 40-74 years attending general practitioners. Odds ratios (OR) and their 95% confidence intervals (CI) for the association between potential risk factors and the prevalence of antibiotic resistance were estimated using generalised estimating equations. RESULTS: Prevalence of E. coli resistance against ampicillin, doxycycline, cotrimoxazole or quinolones was 24%. Current antibiotic use was strongly associated with antibiotic resistance, adjusted OR: 11.1, 95% CI: 2.3-53, but antibiotic resistance was unaffected by antibiotic use stopped weeks before. Recent hospitalisations were the only other significant predictor of an increased prevalence of resistance. CONCLUSIONS: The strong association between current use of antibiotics and colonisation with antibiotic resistant E. coli suggests a major role for selection of resistant strains while using antibiotics that seem to be quickly reversible, though.

Adult↗
PubMed2003

Provider delay among patients with breast cancer in Germany: a population-based study.

PURPOSE: Delaying the diagnosis and initiation of treatment of cancer is likely to result in tumor progression and a worse prognosis. We examined sources and consequences of provider delay among female breast cancer patients in a population-based study in Germany. PATIENTS AND METHODS: Three hundred eighty women, who were ages 18 to 80 years and who had invasive breast cancer, were interviewed with respect to the diagnostic process. Provider delay was defined as time from first presentation to a health care provider until initiation of cancer treatment. RESULTS: Median provider delay was 15 days and did not substantially differ by the specialty of first consulted physician. Delays in the diagnostic work-up were mainly because of erroneous initial suspicion of a benign breast disease or because of time constraints by patients or physicians. Provider delay over 3 months was found in 11% of all breast cancer cases and was associated with patient characteristics such as higher education (odds ratio [OR] = 2.6; 95% confidence interval [CI], 1.3 to 5.4), full-time employment (OR = 2.5; 95% CI, 1.1 to 5.5), family history of breast cancer (OR = 2.8; 95% CI, 1.2 to 6.2), and presenting with a non-breast symptom (OR = 4.3; 95% CI, 1.7 to 10.9). The association between duration of diagnostic work-up and stage at diagnosis was U shaped, with the highest proportions of metastasized breast cancer tumors among women with very short (< 7 days) or very long (> 3 months) duration. CONCLUSION: Diagnostic work-up is within reasonably short time limits among most patients with breast cancer in Germany. Although the association between delay and tumor stage seems to be complex, any delay in diagnostic work-up should be kept to a minimum.

Adult↗
PubMed2003

Relation among alcohol dehydrogenase 2 polymorphism, alcohol consumption, and levels of gamma-glutamyltransferase.

In human beings, alcohol is metabolized primarily by alcohol dehydrogenase 2 (ADH2) and acetaldehyde dehydrogenase 2 (ALDH2). Whereas polymorphisms of the ALDH2 are common in Asian persons, polymorphisms of the ADH2 seem to be more important in Caucasian individuals. The aim of this study was to assess the relation among ADH2 polymorphism, alcohol consumption, and levels of gamma-glutamyltransferase (GGT). The question was examined among 1,663 subjects (736 men and 927 women) participating in a national representative health and nutrition survey (VERA substudy of the German National Nutrition Survey). Alcohol consumption was assessed through responses to a semiquantitative food frequency questionnaire (FFQ), and the ADH2 restriction fragment length polymorphism (RFLP) Mae III and GGT levels were analyzed from frozen serum samples. The relations between the polymorphism and alcohol consumption and between alcohol consumption and GGT levels according to the polymorphism were assessed with the use of descriptive statistics and contingency table analysis. Of the subjects studied, 2.8% were homozygous or heterozygous for the ADH2*2 allele, and high levels of alcohol consumption (>20 g/day) were less common among these subjects (8.5%) than among subjects with the ADH2*1 allele (19.9%). Median levels of GGT increased with increasing levels of alcohol consumption. This increase tended to be stronger among subjects with the ADH2*2 allele than among other subjects, although differences were not statistically significant (P value for interaction=.1) given the small number of subjects with the polymorphism. These results are consistent with the hypothesis that subjects with the ADH2*2 allele, on the one hand, might tend to drink less alcohol but, on the other hand, might be at increased risk of alcohol-related effects on the liver with consumption of larger amounts of alcohol. However, this hypothesis needs to be evaluated among larger population samples.

Adult↗