Pulmonary Hypertension in Patients with Chronic Fibrosing Idiopathic Interstitial Pneumonias

Background Pulmonary hypertension (PH) is a common finding in patients with chronic fibrosing idiopathic interstitial pneumonias (IIP). Little is known about the response to pulmonary vasodilator therapy in this patient population. COMPERA is an international registry that prospectively captures data from patients with various forms of PH receiving pulmonary vasodilator therapies. Methods We retrieved data from COMPERA to compare patient characteristics, treatment patterns, response to therapy and survival in newly diagnosed patients with idiopathic pulmonary arterial hypertension (IPAH) and PH associated with IIP (PH-IIP). Results Compared to patients with IPAH (n = 798), patients with PH-IIP (n = 151) were older and predominantly males. Patients with PH-IIP were treated predominantly with phosphodiesterase-5 inhibitors (88% at entry, 87% after 1 year). From baseline to the first follow-up visit, the median improvement in 6MWD was 30 m in patients with IPAH and 24.5 m in patients with PH-IIP (p = 0.457 for the difference between both groups). Improvements in NYHA functional class were observed in 22.4% and 29.5% of these patients, respectively (p = 0.179 for the difference between both groups). Survival rates were significantly worse in PH-IIP than in IPAH (3-year survival 34.0 versus 68.6%; p<0.001). Total lung capacity, NYHA class IV, and mixed-venous oxygen saturation were independent predictors of survival in patients with PH-IIP. Conclusions Patients with PH-IIP have a dismal prognosis. Our results suggest that pulmonary vasodilator therapy may be associated with short-term functional improvement in some of these patients but it is unclear whether this treatment affects survival

Characterization, treatment patterns, and patient-related outcomes of patients with Fragile X syndrome in Germany: final results of the observational EXPLAIN-FXS study

BACKGROUND: As data on the phenotype, characteristics and management of patients with Fragile X Syndrome (FXS) are limited, we aimed to collect such data in Germany in experienced centres involved in the treatment of such patients. METHODS: EXPLAIN-FXS is a prospective observational (non-interventional) study (registry) performed between April 2013 and January 2016 at 18 sites in Germany. Requirements for patient participation included confirmed diagnosis of FXS by genetic testing (>200 CGG repeats) and written informed consent. Patients were followed for up to 2 years. RESULTS: Seventy-five patients (84.0 % males, mean age 16.7 +/- 14.5 years, ranging from 2 - 82 years) were analysed. The mean 6-item score, determined according to Giangreco (J Pediatr 129:611-614, 1996), was 6.9 +/- 2.5 points. At least one neurological finding each was noted in 53 patients (69.7 %). Specifically, ataxia was noted in 5 patients (6.6 %), lack of fine motor skills in 40 patients, (52.6 %), muscle tonus disorder in 4 patients (5.3 %), and other neurological disorders in 39 patients (51.3 %). Spasticity was not noted in any patient. Seizures were reported in 6 patients (8.1 %), anxiety disorders in 22 patients (30.1 %), depression in 7 patients (9.6 %), ADHD/ADD in 36 patients (49.3 %), impairment of social behavior in 39 patients (53.4 %), and other comorbidities in 23 patients (31.5 %). The mean Aberrant Behaviour Checklist Community Edition (ABC-C) score on behavioral symptoms, obtained in 71 patients at first documentation, was 48.4 +/- 27.8 (median 45.0, range 5-115). The mean visual analogue scale (VAS) score, obtained in 59 patients at first documentation, was 84.9 +/- 14.6 points (median 90; range 50 - 100). CONCLUSIONS: This report describes the largest cohort of patients with FXS in Europe. The reported observations indicate a substantial burden of disease for patients and their caregivers. Based on these observations, an early expert psychiatric diagnosis is recommended for suspected FXS patients. Further recommendations include multimodal and multi-professional management that is tailored to the individual patient's needs

EXPLAIN Fragile-X: an explorative, longitudinal study on the characterization, treatment pathways, and patient-related outcomes of Fragile X Syndrome

BACKGROUND: Fragile X syndrome (FXS), caused by a mutation of the FMR1 gene on the X chromosome, is the most common inherited form of intellectual disability and autism spectrum disorders. Comprehensive data are lacking, however, on the characteristics and management patients with FXS in Germany. METHODS/DESIGN: EXPLAIN is a prospective, observational, longitudinal registry with a non-probability sampling approach. It collects data on patient characteristics, therapeutic interventions, psychosocial parameters (including those of family members and caregivers), quality of life of caregiver and patient, caregiver burden, and health economic parameters, such as hospitalisation time. It is designed to include data from 300 patients in ambulatory care from about 50 centres that employ psychiatrists, paediatricians, neurologists, and other relevant specialists, in Germany. The study was initiated in March, 2013. Patients will be followed for at least two years. DISCUSSION: The registry is expected to provide much-needed data on the characteristics and management of patients with FXS in Germany. It will also allow comparisons with other countries, and will enable gap analyses based on current guidelines for management of these patients. TRIAL REGISTRATION: The ClinicalTrials.gov identifier is NCT01711606

Characteristics, management and attainment of lipid target levels in diabetic and cardiac patients enrolled in Disease Management Program versus those in routine care: LUTZ registry

<p>Abstract</p> <p>Background</p> <p>Since 2002 the sick funds in Germany have widely implemented disease management programs (DMPs) for patients with type 2 diabetes mellitus (DM) and coronary heart disease (CHD). Little is known about the characteristics, treatment and target attainment lipid levels of these patients enrolled in DMPs compared to patients in routine care (non-DMP).</p> <p>Methods</p> <p>In an open, non-interventional registry (LUTZ) in Germany, 6551 physicians documented 15,211 patients with DM (10,110 in DMP, 5101 in routine care) and 14,222 (6259 in DMP, 7963 in routine care) over a follow-up period of 4 months. They received the NCEP ATP III guidelines as a reminder on lipid level targets.</p> <p>Results</p> <p>While demographic characteristics of DMP patients were similar to routine care patients, the former had higher rates of almost all cardiovascular comorbidities. Patients in DMPs received pharmacological treatment (in almost all drug classes) more often than non-DMP patients (e.g. antiplatelets: in DM 27.0% vs 23.8%; in CHD 63.0% vs. 53.6%). The same applied for educational measures (on life style changes and diet etc.). The rate of target level attainment for low density lipoprotein cholesterol (LDL-C) < 100 mg/dl was somewhat higher in DMP patients at inclusion compared to non-DMP patients (DM: 23.9% vs. 21.3%; CHD: 30.6% vs. 23.8%) and increased after 4 months (DM: 38.3% vs. 36.9%; CHD: 49.8% vs. 43.3%). Individual LDL-C target level attainment rates as assessed by the treating physicians were higher (at 4 months in DM: 59.6% vs. 56.5%; CHD: 49.8% vs 43.3%). Mean blood pressure (BP) and HbA_1cvalues were slightly lowered during follow-up, without substantial differences between DMP and non-DMP patients.</p> <p>Conclusion</p> <p>Patients with DM, and (to a greater extent) with CHD in DMPs compared to non-DMP patients in routine care have a higher burden of comorbidities, but also receive more intensive pharmacological treatment and educational measures. The present data support that the substantial additional efforts in DMPs aimed at improving outcomes resulted in quality gains for achieving target LDL-C levels, but not for BP or HbA_1c. Longer-term follow-up is needed to substantiate these results.</p

Interactions between rheumatologists and cardio-/pulmonologists in the assessment and use of outcome measures in pulmonary arterial hypertension related to systemic sclerosis

Objectives: Pulmonary arterial hypertension in patients with systemic sclerosis is a disease involving multiple organ systems. We investigated the differences in perceptions of how to measure PAH-SSc among cardiologists, pulmonologists and rheumatologists. We also examined how a Delphi exercise can improve agreement among these subspecialties. Methods: The outcome measures derived from the recent Delphi survey were used for a detailed analysis of the contribution of the various specialties contributing to it. We compared rheumatologists and cardiologist/pulmonologists with regards to preferences and ratings of various endpoints and the actual use of tools to measure these outcomes. We also examined the effects of the Delphi process among these groups. Results: We could show that the different expert groups each tended to contribute differently to the development of the core set of measures and that interactions in the Delphi process resulted in convergence of rankings. Despite agreement on the high importance of the domains in the Delphi, the use of tools within those domains was sometimes divergent and dependent on specialty. Conclusions: Based on these results, use of differing tools in the diagnosis and treatment of PAH-SSc can be anticipated. Further, the convergence of results provides evidence, for the first time, for the ability of various approaches in these disciplines to reach harmonious endpoints of care for PAHSSc patients. A collaborative, interdisciplinary approach is advantageous for PAH-SSc patients

Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials

Rationale Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. Methods The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology—a non-profit international organisation dedicated to consensus methodology in identification of outcome measures—conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). Results A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Conclusion Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field

oA novel nonparametric approach for estimating cut-offs in continuous risk indicators with application to diabetes epidemiology

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p

Selection effects may account for better outcomes of the German Disease Management Program for type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>The nationwide German disease management program (DMP) for type 2 diabetes was introduced in 2003. Meanwhile, results from evaluation studies were published, but possible baseline differences between DMP and usual-care patients have not been examined. The objective of our study was therefore to find out if patient characteristics as socio-demographic variables, cardiovascular risk profile or motivation for life style changes influence the chance of being enrolled in the German DMP for type 2 diabetes and may therefore account for outcome differences between DMP and usual-care patients.</p> <p>Methods</p> <p>Case control study comparing DMP patients with usual-care patients at baseline and follow up; mean follow-up period of 36 ± 14 months. We used chart review data from 51 GP surgeries. Participants were 586 DMP and 250 usual-care patients with type 2 diabetes randomly selected by chart registry. Data were analysed by multivariate logistic and linear regression analyses. Significance levels were p ≤ 0.05.</p> <p>Results</p> <p>There was a better chance for enrolment if patients a) had a lower risk status for diabetes complications, i.e. non-smoking (odds ratio of 1.97, 95% confidence interval of 1.11 to 3.48) and lower systolic blood pressure (1.79 for 120 mmHg vs. 160 mmHg, 1.15 to 2.81); b) had higher activity rates, i.e. were practicing blood glucose self-monitoring (1.67, 1.03 to 2.76) and had been prescribed a diabetes patient education before enrolment (2.32, 1.29 to 4.19) c) were treated with oral medication (2.17, 1.35 to 3.49) and d) had a higher GP-rated motivation for diabetes education (4.55 for high motivation vs. low motivation, 2.21 to 9.36).</p> <p>Conclusions</p> <p>At baseline, future DMP patients had a lower risk for diabetes complications, were treated more intensively and were more active and motivated in managing their disease than usual-care patients. This finding a) points to the problem that the German DMP may not reach the higher risk patients and b) selection bias may impair the assessment of differences in outcome quality between enrolled and usual-care patients. Suggestions for dealing with this bias in evaluation studies are being made.</p

The disease management program for type 2 diabetes in Germany enhances process quality of diabetes care - a follow-up survey of patient's experiences

<p>Abstract</p> <p>Background</p> <p>In summer 2003 a disease management program (DMP) for type 2 diabetes was introduced on a nationwide basis in Germany. Patient participation and continuity of care within the DMP are important factors to achieve long-term improvements in clinical endpoints. Therefore it is of interest, if patients experience any positive or negative effects of the DMP on their treatment that would support or hamper further participation. The main objective of the study was to find out if the German Disease Management Program (DMP) for type 2 diabetes improves process and outcome quality of medical care for patients in the light of their subjective experiences over a period of one year.</p> <p>Methods</p> <p>Cohort study with a baseline interview and a follow-up after 10.4 ± 0.64 months. Data on process and outcome measures were collected by telephone interviews with 444 patients enrolled and 494 patients not enrolled in the German DMP for type 2 diabetes. Data were analyzed by multivariate logistic regression analyses.</p> <p>Results</p> <p>DMP enrolment was significantly associated with a higher process quality of care. At baseline enrolled patients more often reported that they had attended a diabetes education course (OR = 3.4), have ≥ 4 contacts/year with the attending physician (OR = 3.3), have at least one annual foot examination (OR = 3.1) and one referral to an ophthalmologist (OR = 3.4) and possess a diabetes passport (OR = 2.4). Except for the annual referral to an ophthalmologist these parameters were also statistically significant at follow-up. In contrast, no differences between enrolled and not enrolled patients were found concerning outcome quality indicators, e.g. self-rated health, Glycated hemoglobin (GHb) and blood pressure. However, 16-36% of the DMP participants reported improvements of body weight and/or GHb and/or blood pressure values due to enrolment - unchanged within one year of follow-up.</p> <p>Conclusions</p> <p>In the light of patient's experiences the DMP enhances the process quality of medical care for type 2 diabetes in Germany. The lack of significant differences in outcome quality between enrolled and not enrolled patients might be due to the short program duration. Our data suggest that the DMP for type 2 diabetes should not be withdrawn unless an evidently more promising approach is found.</p

Impact of time since last caloric intake on blood glucose levels

Blood glucose (BG) is usually measured after a caloric restriction of at least 8 h; however evidence-based recommendations for the duration of a fasting status are missing. Here we analyze the effect of fasting duration on levels of BG to determine the minimal fasting duration to achieve comparable BG levels to conventional fasting measurements. We used data of a cross-sectional study on primary care patients, performed in October 2005. We included 28,024 individuals (age-range 18–99 years; 63% women) without known diabetes mellitus and without missing data for BG and fasting status. We computed general linear models, adjusting for age, sex, time of blood withdrawal, systolic blood pressure, waist circumference, total- and HDL-cholesterol, physical activity, smoking, intake of beta-blocker and alcohol. We tested the intra-individual variability with respect to fasting status. Overall, the mean BG differed only slightly between individuals fasting ≥8 h and those fasting <8 h (men: 5.1 ± 0.8 mmol/L versus 5.2 ± 1.2 mmol/L; women: 4.9 ± 0.7 mmol/L, 5.0 ± 1.0 mmol/L). After 3 h of fasting differences of BG diminished in men to −0.08 mmol/L (95%-CI: −0.15; −0.01 mmol/L), in women to −0.07 mmol/L (−0.12; −0.03 mmol/L) compared to individuals fasting ≥8 h. Noteworthy, age, time of day of blood withdrawal, physical activity, and intake of hard liquor influenced BG levels considerably. Our data challenge the necessity for a fasting duration of ≥8 h when measuring blood glucose, suggesting a random sampling or a fasting duration of 3 h as sufficient. Rather, our study indicates that essentially more effort on the assessment of additional external/internal factors on BG levels is necessary