Biomedical subjects

Thomas Kohlmann

Publications and source records attributed to Thomas Kohlmann.

14 recordsLinked to original sources

PubMed2026

Time to subsequent therapy (TTST) as an endpoint in clinical studies: development of standardized documentation of subsequent therapy through systematic literature review, expert interviews, and Delphi survey.

BACKGROUND: The endpoint Time to Subsequent Therapy (TTST) is an intermediate endpoint used in research and regulatory assessments. TTST denotes initiation of subsequent therapy and is a clearly definable, clinically relevant event for healthcare professionals. However, it has not been systematically established to which extent TTST is subjectively meaningful to patients. The objective of this study was to define TTST as a patient-relevant intermediate endpoint. METHODS: The study examined five oncological indications (breast cancer, prostate cancer, melanoma, multiple myeloma, and non-small cell lung cancer) using a systematic literature review, analysis of case report forms used in international randomized controlled trials, review of German Federal Joint Committee (G-BA) documents, semi-structured interviews and a two-stage Delphi survey with healthcare professionals, patients, and relatives. RESULTS: A total of 35 individuals participated in qualitative interviews. Most of them rated TTST as particularly significant. The Delphi Survey included 264 interviewees in round one, and 117 in round two. Patient-relevance of TTST was confirmed by 81% of respondents (95% confidence interval 76%, 85%). Nine treatment scenarios that justify TTST were identified. To capture patient-relevance, prospective collection of reasons for and consequences of therapy change are required. A checklist with standardized response formats plus free-text fields was developed: a comprehensive master checklist for flexible, complete documentation and a short version focused on therapy change-specific items. CONCLUSIONS: TTST is an intermediate endpoint whose systematic documentation of characteristics demonstrating patient-relevance can be standardized in research and clinical practice using the developed checklists.

Humans↗

PubMed2006

Gender imbalance and risk factor interactions in heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is caused by antibodies against a "self" protein-platelet factor 4-bound to heparin. We observed an overrepresentation of the female gender in 290 patients who developed HIT after cardiac or orthopedic surgery compared with the representation found in national databases (study 1). Therefore, we investigated gender imbalance in HIT by logistic regression analysis of a randomized controlled trial of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) (study 2), and we analyzed individual patient data from 7 prospective studies comparing HIT frequency between UFH and LMWH, evaluating effects of gender, heparin (UFH vs LMWH), and patient type (surgical vs medical) (study 3). All 3 studies showed female overrepresentation, which for study 3 was a common odds ratio (OR) of 2.37 (95% confidence interval [95% CI], 1.37-4.09; P = .0015). Study 3 also showed an interaction between gender, heparin, and patient type. Although UFH was more likely than LMWH to cause HIT (P < .0001), this effect was predominantly seen in women compared with men (common OR, 9.22 vs 1.83; P = .020) and in surgical patients compared with medical patients (common OR, 13.93 vs 1.75; P = .005). We conclude that females are at greater risk for HIT and that using LMWH to prevent HIT may have greatest absolute benefit in females undergoing surgical thromboprophylaxis.

Databases, Factual↗

PubMed2006

Does a preceding hand wash and drying time after surgical hand disinfection influence the efficacy of a propanol-based hand rub?

BACKGROUND: Recently, a propanol-based hand rub has been described to exceed the efficacy requirements of the European standard EN 12791 in only 1.5 min significantly. But the effect of a 1 min preceding hand wash and the effect of one additional minute for evaporation of the alcohol after its application on the efficacy after a 1.5 min application time has never been studied. METHODS: We have investigated a propanol-based hand rub (Sterillium, based on 45% propan-2-ol, 30% propan-1-ol and 0.2% mecetronium etilsulfate) in three variations: with (A) and without (B) a 1 min hand wash before the disinfection of 1.5 min with immediate sampling after the disinfection; and (C) without a hand wash before the disinfection but with sampling 1 min after the disinfection. The efficacy of the three variations was compared to the reference treatment of EN 12791. All experiments were performed in a Latin-square design with 20 volunteers. Pre- and post-values (immediate and after 3 hr) were obtained according to EN 12791. RESULTS: The 3 min reference disinfection reduced resident hand bacteria on average by 1.8 log10 steps (immediate effect) and 1.4 log10-steps (sustained effect) respectively. Method A was equally effective as the reference (immediate efficacy: 1.5 log10-steps; sustained efficacy: 1.6 log10-steps). Method B seemed to be more effective (immediate efficacy: 2.3 log10-steps; sustained efficacy: 1.7 log10-steps). Method C revealed the best efficacy (immediate efficacy: 2.3 log10-steps; sustained efficacy: 2.0 log10-steps). A comparison of all three treatment variations and the reference treatment revealed a significant difference for the immediate efficacy (p = 0.026; Friedman test), but not for the sustained efficacy (p = 0.430). A post-hoc-test for the immediate efficacy indicated a significant difference between methods A and C (p < 0.05; Wilcoxon-Wilcox test). Hence, none of the treatment variations was significantly less effective than the reference treatment. CONCLUSION: An application of the propanol-based hand rub for 1.5 min after 1 min hand wash fulfills the efficacy requirements of EN 12791. The efficacy can be improved to some extent by omitting the preceding hand wash and by awaiting the evaporation of the alcohol which is clinical practice anyway. The preceding hand wash has the most negative effect on the immediate effect. Based on our data hands should not be routinely washed before the disinfection period unless there is a good reason for it such as visible soiling.

Anti-Infective Agents, Local↗

PubMed2006

Missing data due to a 'checklist misconception-effect'.

OBJECTIVES: To analyze the extent and relevance of a postulated "checklist misconception-effect" (a specific response pattern characterized by symptom-free persons not checking the "not at all"-category). METHODS: Our data is derived from a survey of blue collar workers (n = 228) who previously had filed in applications for medical rehabilitation benefits. We defined the "checklist misconception-effect" by the following response pattern: (1) at least one missing value and (2) at least one valid item response and (3) no 'not at all' responses. RESULTS: 75% of the responders had complete data, 16.2% a postulated 'checklist misconception-effect'. Substantial co-variations with socio-demographic characteristics or health status indicators could not be found. Additional imputation of missing values under the assumption of a "checklist misconception-effect" led to a reduction of missing data in the somatisation-subscale score from 12.3% to 0.4% compared to a simple manual-based calculation. Correlation with various external criteria (general health perception, level of functioning, depression) remained unchanged. CONCLUSIONS: Ignoring the "checklist misconception-effect" would overestimate symptom load. However, the validity of this effect has still to be proven in methodological studies.

Adult↗

PubMed2006

Subjective health complaints, health-related quality of life and physician visits: results of the study of health in Pomerania (SHIP).

OBJECTIVES: To investigate the relationship between subjective health complaints (SHCs), health-related quality of life and physician visits. METHOD: 3'773 participants of the Study of Health in Pomerania (SHIP) filled questionnaires and were interviewed. Data consisted of 1) 38 statements concerning SHCs, 2) the SF12, and 3) statements concerning visits to 11 different groups of physicians. Factor analysis was done on the SHC data, with a subsequent varimax rotation. Relationships between resulting factors and remaining variables were analysed using 1) the cumulative logit model for the first SF12 item (overall health evaluation), 2) linear regression for the physical and mental sum scores of the SF12, and 3) logistic regression for physician visits. RESULTS: Eight factors have eigenvalues greater than one and together explain 54.2% of total variance. Varimax rotated factors can be interpreted easily. Altogether, these factors, sex and age significantly affect the first SF12 item (Nagelkerke's R2 = 0.27), both sum scores (physical: R2adj. = 0.40; mental: R2adj. = 0.36), and all physician visits (Nagelkerke's R2 between 0.03 and 0.23). CONCLUSIONS: Subjective health complaints are important. Total sum scores of typical SHC questionnaires do not reflect all relevant aspects of SHCs.

Adult↗

PubMed2006

Thyroid disorders in employees of a nuclear power plant.

BACKGROUND: The thyroid gland is a potential target organ for radiation-related damage. The aim of this analysis was to investigate the association between occupational exposure to ionizing radiation and the risk of autoimmune thyroid disease as well as thyroid nodules and dysfunction in workers of a former nuclear power station. METHODS: Seventy-one male power station workers 38 to 57 years of age who had been exposed to a lifetime dose in the upper allowed range (accumulated lifetime dose 70 to 400 mSv) were compared to a population-based sample of 670 males who were not exposed to occupational radiation. Thyroid ultrasound was performed by the same observers. Laboratory parameters were analyzed in a central laboratory. RESULTS: After controlling analyses for age and further relevant confounders no significant differences with respect to thyroid nodules and markers of autoimmune thyroid disease were detected between exposed and nonexposed individuals. However, nuclear power plant employees had higher odds for elevated serum thyrotropin (TSH) levels than the reference group (odds ratio 4.54; 95% confidence interval 1.43; 13.91). CONCLUSIONS: Workers of a nuclear power plant with occupational exposure to ionizing radiation within the upper allowed dose range have an increased risk of elevated serum TSH levels. Further studies are required to confirm possible effects of occupational exposure to radiation on thyroid function.

Adult↗

PubMed2005

International development of the Parents' Index of Quality of Life in Atopic Dermatitis (PIQoL-AD).

OBJECTIVE: The international development of the Parents' Index of Quality of Life in Atopic Dermatitis (PIQoL-AD), a quality of life (QoL) instrument specific to parents of children with atopic dermatitis (AD) is described. METHOD: The instrument was developed simultaneously in several countries. Its content was derived from 65 qualitative interviews with parents in the UK, Netherlands and Italy. The measure was then produced for the UK, Netherlands, Italy, Germany, France, US and Spain. Field-test interviews were conducted with approximately 20 patients in each country to assess face and content validity. A two time-point survey was conducted with between 45 and 328 parents in each country to finalise the instrument through application of the Rasch model and to evaluate the psychometric properties of the final instrument. RESULTS: Application of the Rasch model to the survey data identified the final 28-item version. All language versions had good item fit, test-retest reliability (above 0.85), internal consistency and promising validity. CONCLUSIONS: The PIQoL-AD is a valuable instrument for inclusion in clinical trials and routine clinical practice. It provides distinct and complementary information to that of existing dermatology-specific measures and has been shown to be responsive to changes in QoL in clinical trials.

Child↗

PubMed2005

Reference intervals of serum thyroid function tests in a previously iodine-deficient area.

AIM: We undertook the present study to establish reference data for serum thyroid function tests in a previously iodine-deficient area. METHODS: Data from 4298 individuals, 20-79 years of age were available for the present analysis. Thyroid function (thyrotropin [TSH], free triiodothyronine [FT(3)], and free thyroxine [FT(4)]) and serum autoantibodies to thyroperoxidase (anti-TPOAb) were evaluated from blood samples. Thyroid structure and size were measured by ultrasound. RESULTS: A reference population was selected comprising 1488 persons (825 men) by excluding subjects with known thyroid diseases, and with yet unknown thyroid disorders such as goitre, inhomogeneous thyroid pattern, nodules, hypoechogenicity and anti-TPOAb seropositivity. Reference intervals for serum TSH, FT(3), and FT(4) were 0.25-2.12 mIU/L, 3.8-7.0 pmol/L, and 8.3-18.9 pmol/L, respectively. Reference serum TSH levels were not comparable to the reference values that were recently established for the U.S. population and most reference values slightly differed from the reference values provided by the manufacturers. CONCLUSIONS: The reference ranges of thyroid function tests in this formerly iodine-deficient region are distinct from the reference ranges that were established in areas with iodine sufficiency. Creating a reference population in the present setting should include thyroid ultrasound in order to exclude yet undiagnosed thyroid disorders.

Adult↗

PubMed2005

Clinical features of heparin-induced thrombocytopenia including risk factors for thrombosis. A retrospective analysis of 408 patients.

Immune mediated heparin induced thrombocytopenia (HIT) is a prothrombotic adverse effect of heparin. However, only a subgroup of patients with HIT develops thromboembolic complications. We aimed to identify risk factors for developing HITassociated thrombosis. We analyzed a registry of patients with clinical suspicion of HIT who tested positive using a sensitive functional assay. Patient information was obtained by a standardized questionnaire. By multivariate analysis the association of age, gender, type of patient population, and magnitude of the platelet count decline with the frequency, type (venous or arterial), and temporal pattern of thrombotic events was assessed. In 408 HIT patients we observed predominance of venous thrombosis (2.4:1), with 40% of patients developing a pulmonary embolism. However, in the subgroup of post-cardiovascular surgery patients there was predominance of arterial thrombosis (1:8.5). The type of arterial thrombosis (limb artery thrombosis > thrombotic stroke > myocardial infarction) was the converse of that observed with typical atherothrombotic clots in non-HIT populations. In 59.8% of patients HIT-related thrombosis manifested either on the same day a platelet count decrease >50% was documented (26.3%) or before the decrease in platelet counts (33.5%). The most important risk factors for thrombosis were orthopedic/trauma surgery and the magnitude of platelet count decrease. HIT-associated thrombosis occurs in a considerable proportion of patients before platelet counts decrease by more than 50%.

Adolescent↗

PubMed2005

Longitudinal relationships among transtheoretical model constructs for smokers in the precontemplation and contemplation stages of change.

BACKGROUND: This study examined the pattern, direction, and magnitude of longitudinal relationships among the constructs involved in the Transtheoretical Model (TTM). PURPOSE: The goal was to explore within-TTM relationships to create an integrated structural model that adequately represents the change process. METHOD: Data were collected as part of a representative general adult population study in Germany. A total of 688 smokers in the precontemplation and contemplation stages of change were assessed two times, 6 months apart, with respect to the TTM constructs. Structural equation modeling was used and a step approach was employed to evaluate the relationships between cognitive-affective processes, behavioral processes, the pros and cons of smoking, and self-efficacy, stratified for baseline stage of change. RESULTS: The model-building process resulted in two final structural equation models detailing longitudinal TTM relationships for precontemplation and contemplation. A structural invariance test showed that the precontemplation model also held for the contemplation sample and visa versa. CONCLUSIONS: The TTM constructs can be integrated in a longitudinal structural model. The findings provide empirical support for specific relationships that are posited in the TTM framework. However, differing relationships between TTM constructs for precontemplation and contemplation could not be established.

Adolescent↗

PubMed2004

Can health care utilization explain the association between socioeconomic status and back pain?

STUDY DESIGN: Cross-sectional population-based study. OBJECTIVES: To assess whether the association between socioeconomic status and severe back pain can be explained by the preceding health care utilization for back pain. SUMMARY OF BACKGROUND DATA: The ways in which socioeconomic status affects the occurrence of back pain are unclear. METHODS: Age- and gender-adjusted odds ratios with 95% confidence intervals for the association between indicators of socioeconomic status and severe current back pain (high intensity and/or high disability: no/yes) were investigated in an interview among 770 study participants out of 1113 study participants with a recent history of back pain in a survey among 2731 adults. RESULTS: The point prevalence of severe current back pain (39.8%) was related to educational level and health insurance status. Prior health care utilization for back pain was about 2-fold more prevalent in adults with severe current back pain. Members of private health insurance (odds ratio 0.60, 95% confidence interval 0.37-0.99) were less likely to report prior consultation of a general practitioner for back pain. Members of sick funds for white-collar workers (odds ratio 2.81, 95% confidence interval 1.43-5.51) and private insurance (odds ratio 2.81, 95% confidence interval 1.02-6.24) and individuals with intermediate educational level (odds ratio 1.76, 95% confidence interval 1.05-2.95) utilized more physical therapy for the treatment of back pain. After additionally adjusting for health care utilization, the associations between educational level or health insurance status and severe current back pain remained unchanged. CONCLUSIONS: The data suggest that education, health insurance status, and health care utilization are independently associated with severe current back pain in a society with universal access to health care.

Adult↗

PubMed2003

Factor V Leiden and the risk of stillbirth in a German population.

An association between the factor V Leiden variant and an increased risk of pregnancy loss has been reported. Most previous studies were performed with clinically recruited patients and controls. This approach may cause selection bias. The present analysis was performed with the aim to investigate the association between the factor V Leiden mutation and the risk of stillbirth in a population-based sample. The Study of Health in Pomerania (SHIP) is a survey that was carried out in North East Germany. A random sample from the population aged 20 to 79 years was taken. The total SHIP population comprised 4,310 participants. The presence of the factor V Leiden variant was determined by PCR and Mnl I digestion. The presence of the factor V Leiden variant was neither associated with the number of pregnancies nor with the number of children per women. Data from 1,768 females who had at least one pregnancy with known outcome was available for the present analysis. Seventy-three women (4.1%) reported at least one stillbirth. Women with and without the factor V Leiden mutation did not differ with respect to the number of women with at least one stillbirth (OR for factor V Leiden variant 1.57; 95%-CI 0.76 - 3.25). Furthermore, the number of women with two or more stillbirths, the number of stillbirths per affected woman and the number of stillbirths per number of pregnancies per woman was similar between both genotype groups. In conclusion, there is no association between the factor V Leiden mutation and the risk of stillbirth in a representative population sample.

Adult↗

PubMed2002

The effect of the Val34Leu polymorphism in the factor XIII gene in infants with a birth weight below 1500 g.

OBJECTIVES: The 34Leu polymorphism of the factor XIII gene is associated with a low rate of brain infarction and a higher incidence of primary intracerebral hemorrhage in adults. We evaluated the effect of the polymorphism on the subsequent development of isolated intracranial hemorrhage and white matter disease in preterm infants with a birth weight <1500 g (very low birth weight [VLBW] infants). STUDY DESIGN: We studied 531 VLBW infants and 301 control infants born at term. The factor XIII 34Leu polymorphism was detected by polymerase chain reaction and restriction enzyme digestion. RESULTS: Allele frequencies were not different from term and VLBW infants (Val/Val, 53.1% and 57.8%; Val/Leu, 38.8% and 37.6%; Leu/Leu, 8.0% and 4.5%, respectively). VLBW infants carrying the Leu/Val or Leu/Leu allele had a significant reduced risk of the development of white matter disease (3.6% vs 10.4% in infants without the polymorphism, P =.003). In a multivariate logistic regression analysis, only gestational age <28 weeks (odds ratio, 3.8; 95% confidence interval, 1.9-7.5; P <.001), and the factor XIII 34Leu allele (odds ratio, 0.3; 95% confidence interval, 0.1-0.7; P =.005) had significant prognostic value in predicting subsequent white matter disease. However, VLBW infants who carried the factor XIII 34Leu allele also had a moderately increased risk of the subsequent development of isolated intraventricular hemorrhage (14.3% vs 10.1% in infants without the mutation, P =.17). CONCLUSIONS: VLBW infants carrying the factor XIII 34Leu polymorphism had a decreased risk for white matter disorders.

Alleles↗

PubMed2002

Prescription and tolerability of meloxicam in day-to-day practice: postmarketing observational cohort study of 13,307 patients in Germany.

The goal of this study was to obtain data for prescription habits, tolerability for patients at high risk, and clinical effectiveness of meloxicam administered at 7.5 mg and 15 mg for various rheumatic diseases under real world prescribing conditions. This was a 3-month large-scale prospective observational cohort study in 4000 medical practices throughout Germany shortly after the introduction of meloxicam. To be eligible, patients had to have a diagnosis of acute or chronic active rheumatic disease for which nonsteroidal antiinflammatory drug (NSAID) therapy was required according to the prescribing information. In this study, 13,307 patients receiving meloxicam prescriptions (7.5 mg in 65% and 15 mg in 33%) were observed. The diagnoses of these patients included osteoarthritis (61%), rheumatoid arthritis (24%), ankylosing spondylitis (1.6%), and other rheumatic conditions (28%). A substantial proportion of high risk patients were enrolled: 12% with a previous history of a perforation, ulceration, and bleeding (PUB), 24% with at least one concomitant cardiovascular disorder, and 26% receiving concomitant antihypertensive medication. Many of the patients (58%) had received NSAIDs before meloxicam, including patients with insufficient prior treatment effectiveness (43%) and those with NSAID-related adverse drug reactions (21%). In 85% and 94% of the patients, respectively, effectiveness and tolerability were rated as good or very good. Quality of life and daily functions improved in 64% to 84% of the patients. Only 0.8% of the patients reported gastrointestinal (GI) adverse drug reactions. Four uncomplicated cases of gastric ulceration, one serious perforated gastric ulcer, and one serious ileus complication were reported after incorrect use or overdosing of meloxicam. Treatment with the selective cyclooxygenase-2 (COX-2) inhibitor meloxicam in doses of 7.5 mg and 15 mg resulted in meaningful treatment responses under real life conditions, despite inclusion of a substantial number of patients with insufficient effectiveness of previous use of non-COX-2 selective NSAIDs. All major GI toxicity (PUB) observed was owing to the fact that prescribing conditions were not respected appropriately. Despite a selection of high risk patients overall, GI, cardiovascular, and renal tolerability was favorable.

Journal Article↗