Peter Reitmeir

Helmholtz Zentrum München, München, Bavaria, Germany

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Publications (14)70.99 Total impact

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    ABSTRACT: Background Health states can be valued by those who currently experience a health state (experienced health states [EHS]) or by the general public, who value a set of given health states (GHS) described to them. There has been debate over which method is more appropriate when making resource allocation decisions. Objective This article informs this debate by assessing whether differences between these methods have an effect on the mean EQ-5D-3L tariff scores of different patient groups. Methods The European tariff based on GHS valuations was compared with a German EHS tariff. Comparison was made in the context of EQ-5D-3L health states describing a number of diagnosed chronic diseases (stroke, diabetes, myocardial infarction, and cancer) taken from the Cooperative Health Research in the Augsburg Region population surveys. Comparison was made of both the difference in weighting of the dimensions of the EQ-5D-3L and differences in mean tariff scores for patient groups. Results Weighting of the dimensions of the EQ-5D-3L were found to be systematically different. The EHS tariff gave significantly lower mean scores for most, but not all, patient groups despite tariff scores being lower for 213 of 243 EQ-5D-3L health states using the GHS tariff. Differences were found to vary between groups, with the largest change in difference being 5.45 in the multiple stoke group. Conclusions The two tariffs have systematic differences that in certain patient groups could drive the results of an economic evaluation. Therefore, the choice as to which is used may be critical when making resource allocation decisions.
    Value in Health 01/2014; · 2.19 Impact Factor
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    ABSTRACT: BACKGROUND: To date, there is hardly any study focussing on the question how the concept of HRQL could deepen our understanding of health inequalities. The study aims at describing this potential by analysing data for adults from Germany. METHODS: The analyses are based on three national, representative surveys conducted from 2006 to 2008. HRQL was assessed by the EuroQol-5D (EQ-5D), the descriptive part (problems in five dimensions) and the valuation of health by visual analogue scale (VAS) rendering a value between '0' (worst) and '100' (best imaginable). The major independent variable is educational level (high vs. low). Four other variables were included (i.e. age, sex, per capita income and chronic disease). Multivariate analyses were performed by logistic and linear regression. RESULTS: Data were available for 5676 persons aged ≥20 years (response rate 73%). The prevalence of 'moderate or severe problems' is especially high in the dimension 'pain/discomfort' (low resp. high educational level: 46.3% resp. 25.0%). The mean VAS-value is 79.8 (low resp. high educational level: 75.3 resp. 83.6). Bivariate and multivariate analyses show that similar differences in VAS-values can be seen even after restricting the analyses to participants with a chronic disease. CONCLUSION: Empirical analyses concerning HRQL could further our understanding of health inequalities. They indicate that low status groups are faced with a double burden, first by increased levels of health impairments, and second by lower levels of HRQL once health is impaired. Thus, the extent of health inequalities could be underestimated if measures of HRQL are not taken into account.
    The European Journal of Public Health 03/2012; · 2.52 Impact Factor
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    ABSTRACT: To compare in patients with inflammatory bowel disease the performance of a value set for the EQ-5D based on experienced health states (EHSs) with value sets based on given health states (GHSs). A value set based on EHSs and valuation by the visual analogue scale (VAS) in the German general population was compared with a German and a U.K. value set, both based on GHSs and time-trade off valuation. Accuracy in the prediction of actual VAS ratings by patients was assessed using correlation and mean absolute error. Construct validity was tested by correlation with established disease activity indices and test-retest reliability by intraclass correlation between two measurements. Data originated from a survey of 270 patients with Crohn's disease and 232 patients with ulcerative colitis. EHS-VAS correlates best with actual VAS ratings for all patients but not for all subgroups. EHS-VAS has the lowest mean absolute error for almost all analyzed groups except for measured differences between two time points. Regarding test-retest reliability in all patients, EHS-VAS correlations were closest to those of actual VAS ratings. EHS-VAS renders experience-based valuations but not decision utilities. GHS-based approaches cover severe health states more extensively, but study patients reported health states similar to those of a general population. Compared to GHS time-trade off value sets, the EHS-VAS value set predicted EQ-5D VAS valuations by patients with inflammatory bowel disease equally well and partly better. It performed partly better with respect to test-retest reliability and the same with respect to construct validity.
    Value in Health 01/2012; 15(1):151-7. · 2.19 Impact Factor
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    ABSTRACT: Delineation of the immune correlates of protection in natural infection or after vaccination is a mandatory step for vaccine development. Although the most recent techniques allow a sensitive and specific detection of the cellular immune response, a consensus on the best strategy to assess their magnitude and breadth is yet to be reached. Within the AIDS Vaccine Integrated Project (AVIP http://www.avip-eu.org) we developed an antigen scanning strategy combining the empirical-based approach of overlapping peptides with a vast array of database information. This new system, termed Variable Overlapping Peptide Scanning Design (VOPSD), was used for preparing two peptide sets encompassing the candidate HIV-1 vaccine antigens Tat and Nef. Validation of the VOPSD strategy was obtained by direct comparison with 15mer or 20mer peptide sets in a trial involving six laboratories of the AVIP consortium. Cross-reactive background responses were measured in 80 HIV seronegative donors (HIV-), while sensitivity and magnitude of Tat and Nef-specific T-cell responses were assessed on 90 HIV+ individuals. In HIV-, VOPSD peptides generated background responses comparable with those of the standard sets. In HIV-1+ individuals the VOPSD pools showed a higher sensitivity in detecting individual responses (Tat VOPSD vs. Tat 15mers or 20mers: p≤0.01) as well as in generating stronger responses (Nef VOPSD vs. Nef 20mers: p<0.001) than standard sets, enhancing both CD4 and CD8 T-cell responses. Moreover, this peptide design allowed a marked reduction of the peptides number, representing a powerful tool for investigating novel HIV-1 candidate vaccine antigens in cohorts of HIV-seronegative and seropositive individuals.
    Journal of immunological methods 09/2011; 375(1-2):46-56. · 2.35 Impact Factor
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    ABSTRACT: Topical calcineurin inhibitors are licensed for the treatment of atopic dermatitis; however, the efficacy of tacrolimus in cutaneous lupus erythematosus (CLE) has only been shown in single case reports. In a multicenter, randomized, double-blind, vehicle-controlled trial, we sought to evaluate the efficacy of tacrolimus 0.1% ointment for skin lesions in CLE. Thirty patients (18 female, 12 male) with different subtypes of CLE were included, and two selected skin lesions in each patient were treated either with tacrolimus 0.1% ointment or vehicle twice daily for 12 weeks. The evaluation included scoring of clinical features, such as erythema, hypertrophy/desquamation, edema, and dysesthesia. Significant improvement (P < .05) was seen in skin lesions of CLE patients treated with tacrolimus 0.1% ointment after 28 and 56 days, but not after 84 days, compared with skin lesions treated with vehicle. Edema responded most rapidly to tacrolimus 0.1% ointment and the effect was significant (P < .001) in comparison to treatment with vehicle after 28 days. Clinical score changes in erythema also showed remarkable improvement (P < .05) after 28 days, but not after 56 and 84 days. Moreover, patients with lupus erythematosus tumidus revealed the highest degree of improvement. None of the patients with CLE demonstrated any major side effects. The study was limited by the small sample size. Explorative subgroup analyses revealed that topical application of tacrolimus 0.1% ointment may provide at least temporary benefit, especially in acute, edematous, non-hyperkeratotic lesions of CLE patients, suggesting that calcineurin inhibitors may represent an alternative treatment for the various disease subtypes.
    Journal of the American Academy of Dermatology 07/2011; 65(1):54-64, 64.e1-2. · 4.91 Impact Factor
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    ABSTRACT: Engineered nanoparticles (ENPs) are produced and used in increasing quantities for industrial products, food, and drugs. The fate of ENPs after usage and impact on health is less known. Especially as air pollution, suspended nanoparticles have raised some attention, causing diseases of the lung and cardiovascular system. Human health risks may arise from inhalation of ENPs with associated inflammation, dispersion in the body, and exposure of vulnerable organs (e.g., heart, brain) and tissues with associated toxicity. However, underlying mechanisms are largely unknown. Furthermore future use of ENPs in therapeutic applications is being researched. Therefore knowledge about potential cardiovascular risks due to exposure to ENPs is highly demanded, but there are no established biological testing models yet. Therefore, we established the isolated beating heart (Langendorff heart) as a model system to study cardiovascular effects of ENPs. This model enables observation and analysis of electrophysiological parameters over a minimal time period of 4 h without influence by systemic effects and allows the determination of stimulated release of substances under influence of ENPs. We found a significant dose and material dependent increase in heart rate accompanied by arrhythmia evoked by ENPs made of flame soot (Printex 90), spark discharge generated soot, anatas (TiO(2)), and silicon dioxide (SiO(2)). However, flame derived SiO(2) (Aerosil) and monodisperse polystyrene lattices exhibited no effects. The increase in heart rate is assigned to catecholamine release from adrenergic nerve endings within the heart. We propose the isolated Langendorff heart and its electrophysiological characterization as a suitable test model for studying cardiovascular ENP toxicity.
    ACS Nano 06/2011; 5(7):5345-53. · 12.06 Impact Factor
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    ABSTRACT: Lung mucociliary clearance is impaired in patients with chronic obstructive pulmonary disease (COPD). Treatment guidelines recommend that patients with COPD receive maintenance therapy with long-acting beta-agonists and anticholinergic agents. Twenty-four patients with mild to moderate COPD received formoterol (12 μg, twice daily from Turbuhaler® dry powder inhaler (DPI)) or tiotropium (18 μg, once daily from Handihaler® DPI) for 14 days. They also received single doses of formoterol, tiotropium, salbutamol (200 μg) and placebo. A radioaerosol technique was used to assess the effects on mucus clearance of 14 days treatment with formoterol or tiotropium, as well as single doses of these drugs. The 4 h whole lung retention of radioaerosol was significantly higher after 14 days treatment with tiotropium (P = 0.016), but not after 14 days treatment with formoterol. However, patients bronchodilated after 14 days treatment with both drugs, so that the deposited radioaerosol may have had an increased distance to travel in order to be cleared by mucociliary action. A single dose of formoterol enhanced radioaerosol clearance significantly compared to other single dose treatments (P < 0.05). Formoterol (12 μg) enhances mucus clearance in patients with mild to moderate COPD when given as a single dose, and may do so when given for 14 days. Studies of longer duration would be needed in order to assess the effects of the study drugs on mucus clearance when they are used for long-term maintenance therapy.
    Respiratory medicine 03/2011; 105(6):900-6. · 2.33 Impact Factor
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    ABSTRACT: Inhalation of fine particulate matter (<2.5 μm; fine PM) has been shown to increase the risk for cardiovascular events. In this letter, we reappraise the role of tissue factor (TF) antigen and we also summarize changes in measured coagulation proteins in humans and rodents by other studies with fine PM. By considering all studies including ours, we conclude that monitoring the overall coagulation state by measuring capacity assays such as thrombin generation, and quantification of TF activity would be more suitable than determining single coagulation proteins (such as TF antigen) in order to better assess the systemic prothrombotic effects of fine PM.
    Particle and Fibre Toxicology 03/2011; 8:12; author reply 12. · 9.18 Impact Factor
  • Reiner Leidl, Peter Reitmeir
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    ABSTRACT: Decision makers responsible for allocation of healthcare resources may require that health states are valued by the population for whom they are making decisions. To achieve this, health-state descriptions can be combined with a value set that reflects the valuations of the target population. In the decision-utility approach, such a value set is at least partly based on wants and expectations regarding given health states. This may reflect aspects different from the health state experienced and valued by a respondent. To derive a value set that is completely based on experienced health states, emphasising the patient's perspective, and test its predictive performance in comparison with established approaches. Problem descriptions and rating scale valuations of the EQ-5D were drawn from two representative German population surveys in 2006 and 2007. Two models based on given health states but differing in valuation method (1a, b) were analysed, along with three models based on experienced health states: (2) ordinary least squares regression; (3) scale-transformed regression; and (4) a generalized linear model with binomial error distribution and constraint parameter estimation. The models were compared with respect to issues in specification, and accuracy in predicting the actual valuations of experienced health states in a new data set, using correlation, mean error and ranking measures for the latter. In addition, the impact of standardizing experience-based index models for age and sex of the subjects was investigated. Models 1 (a, b), 2 and 3 partly led to plausible and comparable parameter estimates, but also led to problems of insignificance and inconsistencies in some of the estimates. Model 4 achieved consistency and featured partly equivalent and partly better predictive accuracy. Using this model, mean valuations of health states were much better predicted by the experience-based approach than by the decision-utility approach, especially for health states that frequently (>10) occurred in the population sample. Standardizing the experience-based index models for age and sex further improved predictive accuracy and strengthened the position of model 4. A value set for the EQ-5D can be plausibly estimated from experience-based valuations. The approach offers an alternative to decision makers who prefer experience-based valuation over decision utilities in the measurement of health outcome. Although usefulness in population samples was shown, use in a clinical context will first require indication-specific tests. Current limitations include use in a general population only, and a restricted range of health states covered.
    PharmacoEconomics 01/2011; 29(6):521-34. · 2.86 Impact Factor
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    ABSTRACT: Several epidemiological studies associated exposure to increased levels of particulate matter in Augsburg, Germany with cardiovascular mortality and morbidity. To elucidate the mechanisms of cardiovascular impairments we investigated the cardiopulmonary responses in spontaneously hypertensive rats (SHR), a model for human cardiovascular diseases, following intratracheal instillation of dust samples from Augsburg. 250 μg, 500 μg and 1000 μg of fine ambient particles (aerodynamic diameter <2.5 μm, PM₂(.)₅-AB) collected from an urban background site in Augsburg during September and October 2006 (PM₂(.)₅ 18.2 μg/m³, 10,802 particles/cm3) were instilled in 12 months old SHRs to assess the inflammatory response in bronchoalveolar lavage fluid (BALF), blood, lung and heart tissues 1 and 3 days post instillation. Radio-telemetric analysis was performed to investigate the cardiovascular responses following instillation of particles at the highest dosage based on the inflammatory response observed. Exposure to 1000 μg of PM₂(.)₅-AB was associated with a delayed increase in delta mean blood pressure (ΔmBP) during 2(nd)-4(th) day after instillation (10.0 ± 4.0 vs. -3.9 ± 2.6 mmHg) and reduced heart rate (HR) on the 3rd day post instillation (325.1 ± 8.8 vs. 348.9 ± 12.5 bpm). BALF cell differential and inflammatory markers (osteopontin, interleukin-6, C-reactive protein, and macrophage inflammatory protein-2) from pulmonary and systemic level were significantly induced, mostly in a dose-dependent way. Protein analysis of various markers indicate that PM₂(.)₅-AB instillation results in an activation of endothelin system (endothelin1), renin-angiotensin system (angiotensin converting enzyme) and also coagulation system (tissue factor, plasminogen activator inhibitor-1) in pulmonary and cardiac tissues during the same time period when alternation in ΔmBP and HR have been detected. Our data suggests that high concentrations of PM₂(.)₅-AB exposure triggers low grade PM mediated inflammatory effects in the lungs but disturbs vascular homeostasis in pulmonary tissues and on a systemic level by affecting the renin angiotensin system, the endothelin system and the coagulation cascade. These findings are indicative for promotion of endothelial dysfunction, atherosclerotic lesions, and thrombogeneis and, thus, provide plausible evidence that susceptible-predisposed individuals may develop acute cardiac events like myocardial infarction when repeatedly exposed to high pollution episodes as observed in epidemiological studies in Augsburg, Germany.
    Particle and Fibre Toxicology 09/2010; 7:27. · 9.18 Impact Factor
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    ABSTRACT: Long-term survival of HIV-1 infected individuals is usually achieved by continuous administration of combination antiretroviral therapy (ART). An exception to this scenario is represented by HIV-1 infected nonprogressors (NP) which maintain relatively high circulating CD4+ T cells without clinical symptoms for several years in the absence of ART. Several lines of evidence indicate an important role of the T-cell response in the modulation of HIV-1 infection during the acute and chronic phase of the disease. We analyzed the functional and the differentiation phenotype of Nef- and Tat-specific CD8+ T cells in a cohort of HIV-1 infected NP in comparison to progressors, ART-treated seropositive individuals and individuals undergoing a single cycle of ART interruption. We observed that a distinctive feature of NP is the presence of Nef-specific CD45RA+ CD8+ T cells secreting MIP-1beta but not IFN-gamma. This population was present in 7 out of 11 NP. CD45RA+ IFN-gammaneg MIP-1beta+ CD8+ T cells were not detected in HIV-1 infected individuals under ART or withdrawing from ART and experiencing a rebounding viral replication. In addition, we detected Nef-specific CD45RA+ IFN-gammaneg MIP-1beta+ CD8+ T cells in only 1 out of 10 HIV-1 infected individuals with untreated progressive disease. The novel antigen-specific CD45RA+ IFN-gammaneg MIP-1beta+ CD8+ T cell population represents a new candidate marker of long-term natural control of HIV-1 disease progression and a relevant functional T-cell subset in the evaluation of the immune responses induced by candidate HIV-1 vaccines.
    AIDS Research and Therapy 01/2010; 7:20. · 2.54 Impact Factor
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    ABSTRACT: The EuroQol (EQ)-5D questionnaire is a generic instrument measuring health-related quality of life. Its validity, reliability, and responsiveness were assessed in a large sample of Crohn's disease (CD) and ulcerative colitis (UC) patients. The EQ-5D was completed initially (270 CD and 232 UC subjects) and after 4 weeks (447 subjects) with a transition question rating health change. Responsiveness of EQ visual analog scale (EQ-VAS) and the United Kingdom (UK-index) and German EQ-5D index (EQ-index) scores to reported changes in health was evaluated by standardized response means (SRM) and meaningful differences (MDs). EQ-VAS and EQ-index scores correlated well with disease activity indices and differed significantly between active disease and remission groups. All scores were reliable in test-retest (ICC: EQ-VAS: 0.89; UK-index: 0.76; German EQ-index: 0.72). According to SRM, EQ-VAS was more responsive for deterioration in health than for improvement in health and was more responsive than index scores. Index scores were most responsive for deterioration in health in subjects in remission and for improved health in subjects with active disease. MDs for improved health (EQ-VAS: 10.9; UK EQ-index: 0.076; German EQ-index: 0.050) and deteriorated health (EQ-VAS: -14.4; UK EQ-index: -0.109; German EQ-index: -0.067) were significant, but MD of EQ-VAS also differed significantly according to disease activity. The EQ-5D generates valid, reliable, and responsive preference-based evaluations of health in CD and UC. EQ-VAS scores were more responsive than EQ-5D index scores. Thus, small health differences that are important from the patient's perspective may not be reflected in the EQ-index.
    Inflammatory Bowel Diseases 06/2009; 16(1):42-51. · 5.12 Impact Factor
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    ABSTRACT: In the mouse Pax6 function is critical in a dose-dependent manner for proper eye development. Pax6 contiguous gene deletions were shown to be homozygous lethal at an early embryonic stage. Heterozygotes express belly spotting and extreme microphthalmia. The eye phenotype is more severe than in heterozygous Pax6 intragenic null mutants, raising the possibility that deletions are functionally different from intragenic null mutations or that a region distinct from Pax6 included in the deletions affects eye phenotype. We recovered and identified the exact regions deleted in three new Pax6 deletions. All are homozygous lethal at an early embryonic stage. None express belly spotting. One expresses extreme microphthalmia and two express the milder eye phenotype similar to Pax6 intragenic null mutants. Analysis of Pax6 expression levels and the major isoforms excluded the hypothesis that the deletions expressing extreme microphthalmia are directly due to the action of Pax6 and functionally different from intragenic null mutations. A region distinct from Pax6 containing eight genes was identified for belly spotting. A second region containing one gene (Rcn1) was identified for the extreme microphthalmia phenotype. Rcn1 is a Ca(+2)-binding protein, resident in the endoplasmic reticulum, participates in the secretory pathway and expressed in the eye. Our results suggest that deletion of Rcn1 directly or indirectly contributes to the eye phenotype in Pax6 contiguous gene deletions.
    Genetics 06/2009; 182(4):1077-88. · 4.39 Impact Factor
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    ABSTRACT: Exposure to particulate matter is a risk factor for cardiopulmonary disease but the underlying molecular mechanisms remain poorly understood. In the present study we sought to investigate the cardiopulmonary responses on spontaneously hypertensive rats (SHRs) following inhalation of UfCPs (24 h, 172 mug.m-3), to assess whether compromised animals (SHR) exhibit a different response pattern compared to the previously studied healthy rats (WKY). Cardiophysiological response in SHRs was analyzed using radiotelemetry. Blood pressure (BP) and its biomarkers plasma renin-angiotensin system were also assessed. Lung and cardiac mRNA expressions for markers of oxidative stress (hemeoxygenase-1), blood coagulation (tissue factor, plasminogen activator inhibitor-1), and endothelial function (endothelin-1, and endothelin receptors A and B) were analyzed following UfCPs exposure in SHRs. UfCPs-mediated inflammatory responses were assessed from broncho-alveolar-lavage fluid (BALF). Increased BP and heart rate (HR) by about 5% with a lag of 1-3 days were detected in UfCPs exposed SHRs. Inflammatory markers of BALF, lung (pulmonary) and blood (systemic) were not affected. However, mRNA expression of hemeoxygenase-1, endothelin-1, endothelin receptors A and B, tissue factor, and plasminogen activator inhibitor showed a significant induction (~2.5-fold; p < 0.05) with endothelin 1 being the maximally induced factor (6-fold; p < 0.05) on the third recovery day in the lungs of UfCPs exposed SHRs; while all of these factors - except hemeoxygenase-1 - were not affected in cardiac tissues. Strikingly, the UfCPs-mediated altered BP is paralleled by the induction of renin-angiotensin system in plasma. Our finding shows that UfCPs exposure at levels which does not induce detectable pulmonary neutrophilic inflammation, triggers distinct effects in the lung and also at the systemic level in compromised SHRs. These effects are characterized by increased activity of plasma renin-angiotensin system and circulating white blood cells together with moderate increases in the BP, HR and decreases in heart rate variability. This systemic effect is associated with pulmonary, but not cardiac, mRNA induction of biomarkers reflective of oxidative stress; activation of vasoconstriction, stimulation of blood coagulation factors, and inhibition of fibrinolysis. Thus, UfCPs may cause cardiovascular and pulmonary impairment, in the absence of detectable pulmonary inflammation, in individuals suffering from preexisting cardiovascular diseases.
    Particle and Fibre Toxicology 01/2009; 5:19. · 9.18 Impact Factor