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author:("loesche, Jens")
1.  Testosterone, Sex Hormone-Binding Globulin and the Metabolic Syndrome in Men: An Individual Participant Data Meta-Analysis of Observational Studies 
PLoS ONE  2014;9(7):e100409.
Background
Low total testosterone (TT) and sex hormone-binding globulin (SHBG) concentrations have been associated with the metabolic syndrome (MetS) in men, but the reported strength of association varies considerably.
Objectives
We aimed to investigate whether associations differ across specific subgroups (according to age and body mass index (BMI)) and individual MetS components.
Data sources
Two previously published meta-analyses including an updated systematic search in PubMed and EMBASE.
Study Eligibility Criteria
Cross-sectional or prospective observational studies with data on TT and/or SHBG concentrations in combination with MetS in men.
Methods
We conducted an individual participant data meta-analysis of 20 observational studies. Mixed effects models were used to assess cross-sectional and prospective associations of TT, SHBG and free testosterone (FT) with MetS and its individual components. Multivariable adjusted odds ratios (ORs) and hazard ratios (HRs) were calculated and effect modification by age and BMI was studied.
Results
Men with low concentrations of TT, SHBG or FT were more likely to have prevalent MetS (ORs per quartile decrease were 1.69 (95% CI 1.60-1.77), 1.73 (95% CI 1.62-1.85) and 1.46 (95% CI 1.36-1.57) for TT, SHBG and FT, respectively) and incident MetS (HRs per quartile decrease were 1.25 (95% CI 1.16-1.36), 1.44 (95% 1.30-1.60) and 1.14 (95% 1.01-1.28) for TT, SHBG and FT, respectively). Overall, the magnitude of associations was largest in non-overweight men and varied across individual components: stronger associations were observed with hypertriglyceridemia, abdominal obesity and hyperglycaemia and associations were weakest for hypertension.
Conclusions
Associations of testosterone and SHBG with MetS vary according to BMI and individual MetS components. These findings provide further insights into the pathophysiological mechanisms linking low testosterone and SHBG concentrations to cardiometabolic risk.
doi:10.1371/journal.pone.0100409
PMCID: PMC4096400  PMID: 25019163
2.  Investigating significant health trends in idiopathic pulmonary fibrosis (INSIGHTS-IPF): rationale, aims and design of a nationwide prospective registry 
BMJ Open Respiratory Research  2014;1(1):e000010.
Background
Guidelines on the diagnosis and management of idiopathic pulmonary fibrosis (IPF), a rare manifestation of chronic progressive fibrosing interstitial pneumonia, have been updated by ATS/ERS/JRS/ALAT in 2011. In Europe, data are limited on the characteristics and management of such patients.
Methods/design
Investigating significant health trends (INSIGHTS)-IPF is a prospective observational longitudinal registry designed to describe the characteristics and management of newly diagnosed (incident) and prevalent patients with IPF on the long term. The registry uses a non-probability sampling approach to collect data on characteristics, therapeutic interventions, health-related quality of life and health economic parameters. At least 500 patients in ambulatory care will be included consecutively in about 30 centres. The study has been initiated in November 2012, and currently (December 2013) follows 344 patients. ClinTrials.gov identifier is NCT01695408.
Discussion
INSIGHTS-IPF documents one of the largest IPF cohorts in Europe. The registry is expected to provide much-needed data on the characteristics and management situation of patients with IPF in Germany. It will allow comparisons with other countries. Gap analyses based on current guidelines for management of these patients will be possible.
doi:10.1136/bmjresp-2013-000010
PMCID: PMC4212719  PMID: 25478169
Rare lung diseases; Interstitial Fibrosis
3.  Mapping the EQ-5D index by UPDRS and PDQ-8 in patients with Parkinson’s disease 
Background
Clinical studies employ the Unified Parkinson’s Disease Rating Scale (UPDRS) to measure the severity of Parkinson’s disease. Evaluations often fail to consider the health-related quality of life (HrQoL) or apply disease-specific instruments. Health-economic studies normally use estimates of utilities to calculate quality-adjusted life years. We aimed to develop an estimation algorithm for EuroQol- 5 dimensions (EQ-5D)-based utilities from the clinical UPDRS or disease-specific HrQoL data in the absence of original utilities estimates.
Methods
Linear and fractional polynomial regression analyses were performed with data from a study of Parkinson’s disease patients (n=138) to predict the EQ-5D index values from UPDRS and Parkinson’s disease questionnaire eight dimensions (PDQ-8) data. German and European weights were used to calculate the EQ-5D index. The models were compared by R2, the root mean square error (RMS), the Bayesian information criterion, and Pregibon’s link test. Three independent data sets validated the models.
Results
The regression analyses resulted in a single best prediction model (R2: 0.713 and 0.684, RMS: 0.139 and 13.78 for indices with German and European weights, respectively) consisting of UPDRS subscores II, III, IVa-c as predictors. When the PDQ-8 items were utilised as independent variables, the model resulted in an R2 of 0.60 and 0.67. The independent data confirmed the prediction models.
Conclusion
The best results were obtained from a model consisting of UPDRS subscores II, III, IVa-c. Although a good model fit was observed, primary EQ-5D data are always preferable. Further validation of the prediction algorithm within large, independent studies is necessary prior to its generalised use.
doi:10.1186/1477-7525-11-35
PMCID: PMC3662160  PMID: 23497005
Parkinson’s disease; Quality of life; EuroQoL/EQ-5D; UPDRS; PDQ-8; Prediction
4.  Changes in the Prevalence, Treatment and Control of Hypertension in Germany? A Clinical-Epidemiological Study of 50.000 Primary Care Patients 
PLoS ONE  2012;7(12):e52229.
Introduction
Medical societies have developed guidelines for the detection, treatment and control of hypertension (HTN). Our analysis assessed the extent to which such guidelines were implemented in Germany in 2003 and 2001.
Methods
Using standardized clinical diagnostic and treatment appraisal forms, blood pressure levels and patient questionnaires for 55,518 participants from the cross-sectional Targets and Essential Data for Commitment of Treatment (DETECT) study (2003) were analyzed. Physician’s diagnosis of hypertension (HTNdoc) was defined as coding hypertension in the clinical appraisal questionnaire. Alternative definitions used were physician’s diagnosis or the patient’s self-reported diagnosis of hypertension (HTNdoc,pat), physician’s or patient’s self-reported diagnosis or a BP measurement with a systolic BP≥140 mmHg and/or a diastolic BP≥90 (HTNdoc,pat,bp) and diagnosis according to the National Health and Nutrition Examination Survey (HTNNHANES). The results were compared with the similar German HYDRA study to examine whether changes had occurred in diagnosis, treatment and adequate blood pressure control (BP below 140/90 mmHg) since 2001. Factors associated with pharmacotherapy and control were determined.
Results
The overall prevalence rate for hypertension was 35.5% according to HTNdoc and 56.0% according to NHANES criteria. Among those defined by NHANES criteria, treatment and control rates were 56.0% and 20.3% in 2003, and these rates had improved from 55.3% and 18.0% in 2001. Significant predictors of receiving antihypertensive medication were: increasing age, female sex, obesity, previous myocardial infarction and the prevalence of comorbid conditions such as coronary heart disease (CHD), hyperlipidemia and diabetes mellitus (DM). Significant positive predictors of adequate blood pressure control were CHD and antihypertensive medication. Inadequate control was associated with increasing age, male sex and obesity.
Conclusions
Rates of treated and controlled hypertension according to NHANES criteria in DETECT remained low between 2001 and 2003, although there was some minor improvement.
doi:10.1371/journal.pone.0052229
PMCID: PMC3532113  PMID: 23284945
6.  Psychometric Properties of the Depression Anxiety and Stress Scale-21 in Older Primary Care Patients 
Journal of affective disorders  2008;110(3):248-259.
The Depression Anxiety Stress Scale (DASS) was designed to efficiently measure the core symptoms of anxiety and depression and has demonstrated positive psychometric properties in adult samples of anxiety and depression patients and student samples. Despite these findings, the psychometric properties of the DASS remain untested in older adults, for whom the identification of efficient measures of these constructs is especially important.
To determine the psychometric properties of the DASS 21-item version in older adults, we analyzed data from 222 medical patients seeking treatment to manage worry. Consistent with younger samples, a three-factor structure best fit the data. Results also indicated good internal consistency, excellent convergent validity, and good discriminative validity, especially for the depression scale. Receiver operating curve analyses indicated that the DASS-21 predicted the diagnostic presence of generalized anxiety disorder and depression as well as other commonly used measures.
These data suggest that the DASS may be used with older adults in lieu of multiple scales designed to measure similar constructs, thereby reducing participant burden and facilitating assessment in settings with limited assessment resources.
doi:10.1016/j.jad.2008.01.023
PMCID: PMC2709995  PMID: 18304648
Depression Anxiety Stress Scale; Older Adults; GAD; Anxiety; Assessment
7.  oA novel nonparametric approach for estimating cut-offs in continuous risk indicators with application to diabetes epidemiology 
Background
Epidemiological and clinical studies, often including anthropometric measures, have established obesity as a major risk factor for the development of type 2 diabetes. Appropriate cut-off values for anthropometric parameters are necessary for prediction or decision purposes. The cut-off corresponding to the Youden-Index is often applied in epidemiology and biomedical literature for dichotomizing a continuous risk indicator.
Methods
Using data from a representative large multistage longitudinal epidemiological study in a primary care setting in Germany, this paper explores a novel approach for estimating optimal cut-offs of anthropomorphic parameters for predicting type 2 diabetes based on a discontinuity of a regression function in a nonparametric regression framework.
Results
The resulting cut-off corresponded to values obtained by the Youden Index (maximum of the sum of sensitivity and specificity, minus one), often considered the optimal cut-off in epidemiological and biomedical research. The nonparametric regression based estimator was compared to results obtained by the established methods of the Receiver Operating Characteristic plot in various simulation scenarios and based on bias and root mean square error, yielded excellent finite sample properties.
Conclusion
It is thus recommended that this nonparametric regression approach be considered as valuable alternative when a continuous indicator has to be dichotomized at the Youden Index for prediction or decision purposes.
doi:10.1186/1471-2288-9-63
PMCID: PMC2754490  PMID: 19744332
8.  CNI-1493 inhibits Aβ production, plaque formation, and cognitive deterioration in an animal model of Alzheimer's disease 
The Journal of Experimental Medicine  2008;205(7):1593-1599.
Alzheimer's disease (AD) is characterized by neuronal atrophy caused by soluble amyloid β protein (Aβ) peptide “oligomers” and a microglial-mediated inflammatory response elicited by extensive amyloid deposition in the brain. We show that CNI-1493, a tetravalent guanylhydrazone with established antiinflammatory properties, interferes with Aβ assembly and protects neuronal cells from the toxic effect of soluble Aβ oligomers. Administration of CNI-1493 to TgCRND8 mice overexpressing human amyloid precursor protein (APP) for a treatment period of 8 wk significantly reduced Aβ deposition. CNI-1493 treatment resulted in 70% reduction of amyloid plaque area in the cortex and 87% reduction in the hippocampus of these animals. Administration of CNI-1493 significantly improved memory performance in a cognition task compared with vehicle-treated mice. In vitro analysis of CNI-1493 on APP processing in an APP-overexpressing cell line revealed a significant dose-dependent decrease of total Aβ accumulation. This study indicates that the antiinflammatory agent CNI-1493 can ameliorate the pathophysiology and cognitive defects in a murine model of AD.
doi:10.1084/jem.20060467
PMCID: PMC2442637  PMID: 18573905

Results 1-8 (8)