Association of Anemia with Clinical Symptoms Commonly Attributed to Anemia-Analysis of Two Population-Based Cohorts.

BACKGROUND: Fatigue, dyspnea, and lack of energy and concentration are commonly interpreted as indicative of symptomatic anemia and may thus play a role in diagnostic and therapeutic decisions. OBJECTIVE: To investigate the association between symptoms commonly attributed to anemia and the actual presence of anemia. METHODS: Data from two independent cohorts of the Study of Health in Pomerania (SHIP) were analyzed. Interview data, laboratory data, and physical examination were individually linked with claims data from the Association of Statutory Health Insurance Physicians. A complete case analysis using logistic regression models was performed to evaluate the association of anemia with symptoms commonly attributed to anemia. The models were adjusted for confounders such as depression, medication, insomnia, and other medical conditions. RESULTS: A total of 5979 participants (53% female, median age 55) were included in the analysis. Of those, 30% reported fatigue, 16% reported lack of energy, 16% reported lack of concentration, and 29% reported dyspnea and/or weakness. Anemia was prevalent in about 6% (379). The symptoms were more prevalent in participants with anemia. However, participants with anemia were older and had a poorer health status. There was no association in multivariate logistic regression models between the symptoms fatigue, lack of concentration, dyspnea, and/or weakness and anemia. Anemia was associated (OR: 1.45; 95% CI: 1.13-1.86) with lack of energy in the multivariate analysis. Other factors such as depression, insomnia, and medication were more strongly associated with the symptoms. CONCLUSION: The clinical symptoms commonly attributed to anemia are unspecific and highly prevalent both in non-anemic and anemic persons. Even in the presence of anemia, other diagnoses should be considered as causes such as depression, heart failure, asthma, and COPD, which are more closely associated with the symptoms. Further diagnostic research is warranted to explore the association of symptoms in different subgroups and settings in order to help clinical decision making.

Referral criteria for chronic kidney disease: implications for disease management and healthcare expenditure-analysis of a population-based sample.

BACKGROUND: Clinical practice guidelines recommend specialist referral according to different criteria. The aim was to assess recommended and observed referral rate and health care expenditure according to recommendations from: • Kidney Disease Improving Global Outcomes (KDIGO,2012) • National Institute for Health and Care Excellence (NICE,2014) • German Society of Nephrology/German Society of Internal Medicine (DGfN/DGIM,2015) • German College of General Practitioners and Family Physicians (DEGAM,2019) • Kidney failure risk equation (NICE,2021) METHODS: Data of the population-based cohort Study of Health in Pomerania were matched with claims data. Proportion of subjects meeting referral criteria and corresponding health care expenditures were calculated and projected to the population of Mecklenburg-Vorpommern. RESULTS: Data from 1927 subjects were analysed. Overall proportion of subjects meeting referral criteria ranged from 4.9% (DEGAM) to 8.3% (DGfN/DGIM). The majority of patients eligible for referral were ≥ 60 years. In subjects older than 60 years, differences were even more pronounced, and rates ranged from 9.7% (DEGAM) to 16.5% (DGfN/DGIM). Estimated population level costs varied between €1,432,440 (DEGAM) and €2,386,186 (DGfN/DGIM). From 190 patients with eGFR < 60 ml/min, 15 had a risk of end stage renal disease > 5% within the next 5 years. CONCLUSIONS: Applying different referral criteria results in different referral rates and costs. Referral rates exceed actually observed consultation rates. Criteria need to be evaluated in terms of available workforce, resources and regarding over- and underutilization of nephrology services.

Validation of Cardiovascular Risk Prediction by the Arriba Instrument.

BACKGROUND: It is recommended in cardiovascular prevention guidelines that treatment should be based on overall cardiovascular risk. The arriba instrument has been widely used for this purpose in Germany. The aim of this study is to validate risk prediction by arriba with the aid of morbidity and mortality data from the population- based Study of Health in Pomerania. METHODS: In a longitudinal analysis, the arriba instrument was used to calculate the 10-year overall cardiovascular risk at baseline for subjects who had not sustained any prior cardiovascular event. Cardiovascular event rates were determined from follow-up data, and discrimination and calibration measures for the risk determination algorithm were calculated. RESULTS: Data from 1973 subjects (mean age 51 ± 13 years, 48% men) were included in the analysis. After a median follow-up of 10.9 years, cardiovascular events had occurred in 196 subjects, or 9.8%. The ratio of predicted to observed event rate was 0.8 (95% confidence interval: [0.5; 1.1]), 1.3 [1.0; 1.8], and 1.1 [0.8; 1.4] for subjects at low, intermediate, and high cardiovascular risk, respectively. Arriba underestimated cardiovascular event rates in women and overestimated them in persons aged 30-44 and 45-59. The area under curve was 0.84 [95% CI 0.81; 0.86]. CONCLUSION: The discrimination scores of the arriba instrument resemble those of SCORE-Germany and PROCAM, but a better adjustment to the target population would be desirable. The results support the recommendation of the German Guideline for Cardiovascular Risk Counseling in General Practice for the use of the arriba instrument. An unresolved problem is the failure to consider intervention effects, resulting in an overall mild overestimation of risk.

The course of thyroid nodules and thyroid volume over a time period of up to 10 years: a longitudinal analysis of a population-based cohort.

OBJECTIVE: Thyroid disorders are common. Information on the long-term progression of morphologic disorders is scarce. The aim of this study was to describe the course of thyroid nodules and volume over a period of up to 10 years. DESIGN AND METHODS: Data from the population-based Study of Health in Pomerania were used for longitudinal analysis of 10 years, on average. Billing data from the Association of Statutory Health Insurance Physicians were matched to the data to exclude participants with thyroid surgery, radioiodine therapy and thyroid carcinoma. Changes in the number and size of thyroid nodules and thyroid volume were observed using ultrasound. RESULTS: A total of 1270 participants were included (53% female, median age at baseline 51 years). The proportion of subjects with at least one thyroid nodule increased from 34.9 to 47.5% after 10 years. The majority of participants had an unchanged or reduced number of nodules. About one-quarter had at least one nodule of size ≥ 1 cm. The proportion of participants with goitre increased from 35 to 37% after 10 years. Nevertheless, individual thyroid volume increased by < 1 mL (95% CI: 0.38-3.66) after adjusting for age and BMI irrespective of thyroid medication. CONCLUSION: Thyroid nodules and goitre are common. After 10 years, the number of nodules did not increase in about 70% of people. This proportion did not differ substantially when excluding people with thyroid medication. Thyroid volume increased slightly over the follow-up period. These changes do not seem clinically relevant. Our results support a more restrictive approach regarding follow-up diagnostics in asymptomatic patients with thyroid nodules or minimally enlarged thyroid.

[Patient safety in the treatment of rheumatic diseases : Laboratory monitoring in methotrexate treatment]. / Patientensicherheit in der Rheumatherapie : Labormonitoring bei Methotrexat.

BACKGROUND: Methotrexate (MTX) is the most commonly prescribed disease-modifying drug in the treatment of rheumatic diseases. Regular laboratory testing is recommended to recognize side effects, such as hepatotoxicity and myelotoxicity as well as decreases in renal function that may cause toxic MTX accumulation. Additionally, folic acid is recommended as prophylaxis against specific side effects. In this study we investigated whether laboratory monitoring and prescription of folic acid took place according to published recommendations. MATERIAL AND METHODS: Claims data from the statutory health insurance from 1 January 2009 to 31 December 2013 were retrospectively analyzed. A total of 40,087 adults with a rheumatic diagnosis (ICD10 codes M05-M18), no malignant disease and no previous MTX prescription within 12 months were extracted from the InGef (Institute for Applied Health Research in Berlin, formerly Health Risk Institute) research database. The frequency of recommended laboratory testing, appointments with rheumatologists and the prescription of folic acid prophylaxis were investigated. RESULTS: Of the patients 12,451 began treatment with MTX in the observation period. Between 42% and 46% of recommended blood counts, liver values and kidney function tests and 14% of urinalyses were performed according to recommendations. Of the patients 84% were seen regularly by a rheumatologist and 74% received a prescription for prophylactic folic acid. Serious conditions potentially resulting from MTX treatment were observed in 0.7-3.5 cases/1000 person years. DISCUSSION: Laboratory monitoring in the context of MTX treatment is carried out less frequently than recommended in the literature. Potential MTX-associated serious complications are rare from a practice perspective. On the one hand solutions are needed for a better coordination of laboratory monitoring. On the other hand more empirical evidence is needed regarding the benefits of laboratory monitoring and the appropriate intervals thereof.

Cerumen Impaction Removal in General Practices: A Comparison of Approved Standard Products.

BACKGROUND: Ear irrigation is a commonly used method for removing earwax in general practice. There is no firm evidence if no pre-treatment is as good as pre-treatment with various standard preparations. AIM: To assess the effectiveness of no pre-treatment compared to pre-treatment with commercially available cerumenolytics and to assess which preparation is best suited for pre-treatment. METHODS: This is a pragmatic observational study of patients with cerumen treated from a single GP with 3 different preparations or no preparation prior to standardized ear irrigation. Generalized linear mixed models with logit link function were performed to assess the effectiveness of pre-treatment with different preparations and no pre-treatment. The models were adjusted for age group (<70, ≥70) and sex. RESULTS: A total of 168 patients (298 ears, 58 % female, median age 65 years) consulted for obstructive cerumen, some of them several times. The cerumen was successfully removed in 70% (208/298). Comparing any preparation to no preparation (aggregated comparison), the odds ratio for complete clearance was 1.35 (95%confidence interval: 0.69-2.65). Comparing the preparations individually, the odds ratio of the docusate-sodium-based preparation was 1.87 (95% CI: 0.79-4.42) indicating a higher effectiveness. Although, not statistically significant. Ear irrigation was less successful for patients aged ≥ 70 years (OR = 0.48, 95% CI: 0.23-0.98). CONCLUSIONS: The aggregated comparison indicates a slight trend toward a higher effectiveness of any pre-treatment compared to no pre-treatment. The effect-size of docusate-sodium-based pre-treatment indicates a higher effectiveness of cerumen impaction removal. Nevertheless, superiority could not be shown conclusively according to the statistical significance given the restricted sample size.

Dual renin-angiotensin-aldosterone blockade: Implementation of published research and Dear Doctor letters in ambulatory care: A retrospective observational study using prescription data.

PURPOSE: This study aims to assess the implementation of published research, contraindications, and warnings on the prescription of dual renin-angiotensin-hormone system (RAS) blockade in ambulatory care in Germany. METHODS: Cohort study based on health claims data of 6.7 million subjects from 2008 to 2015. Yearly prevalence and incidence for dual RAS blockade with (a) angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers (ACEI + ARB) and (b) aliskiren and ACEI or ARB (aliskiren + ACEI/ARB) were calculated. We assessed prescriber specialty and associations between discontinuing dual RAS blockade with specialist (internal medicine, cardiology, nephrology) visits and hospital discharge in the previous year. RESULTS: A total of 2 984 517 patients were included (age 51.4 ± SD 18.4 y, 48.5% male). Prescription rates for ACEI + ARB decreased from 0.6% (n = 17 907) to 0.4% (n = 12 237) and for aliskiren + ACEI/ARB from 0.23% (n = 6634) to 0.03% (n = 818). Incident prescriptions decreased from 0.23% (n = 6705) to 0.19% (n = 5055) (ACE + ARB) and from 0.1% (n = 2796) to 0.005% (n = 142) (aliskiren + ACE/ARB); 59% of ACEI + ARB and 48% of aliskiren + ACE/ARB combinations were prescribed only by one physician. Of those, 73% (ACEI + ARB) and 58% (aliskiren + ACE/ARB) were primary care providers (PCPs). Discontinuing dual RAS blockade was associated with specialist care and hospital discharge in the previous year (specialist care: RR 1.4, 95% CI, 1.3-1.6; hospital visit: RR 1.5, 95% CI, 1.3-1.6). CONCLUSIONS: Our results suggest a delayed uptake of treatment recommendation for ACEI + ARB and a higher impact of Dear Doctor letters addressing PCPs directly compared with published research, contraindications, and warnings. Targeted continuous medical education, practice software alerts, and stronger involvement of pharmacists might improve the implementation of medication safety recommendations in ambulatory care.

Frequency of thyroid function tests and examinations in participants of a population-based study.

BACKGROUND: Thyroid disorders are common in the adult German population. Little is known about guideline implementation in clinical practice and the prevalence of diagnostic procedures in ambulatory care. The study aims to investigate the use of thyroid hormone measurements, thyroid ultrasound, thyroid scintiscan and associated costs in ambulatory care at population level. METHODS: Data were derived from two independent population-based cohorts of the Study of Health In Pomerania (SHIP). Ambulatory billing data from the Association of Statutory Health Insurance Physicians Mecklenburg-Vorpommern were individually linked for the period 2002-2016 with SHIP data. The main outcomes were the frequency of outpatient ultrasound, scintiscan, serum TSH level measurement, free triiodothyronine (fT3) and free thyroxine (fT4) measurement, TSH-receptor-antibodies and microsomal antibodies measurement within 1 year and 3 years prior to the study entrance of the participants. Multinomial logistic regression models were used to assess the association of age, sex, thyroid medication intake and Charlson-Comorbidity-Index with frequency of TSH measurements and ultrasound examinations. RESULTS: A total of 5552 participants (47% male, median age 55) were included in the analysis. 25% (1409/5552) had a diagnosed thyroid disorder or treatment, 40% (2191/5552) had clinical findings based on ultrasound or laboratory testing in SHIP only and 35% (1952/5552) neither a coded thyroid disorder or clinical finding nor thyroid medication. In the total study population 30% (1626/5552) received at least one TSH measurement, 6.8% (378/5552) at least one thyroid ultrasound and 2.6% (146/5552) at least one scintiscan within the past year before the study examination. Tests were performed more frequently in patients with thyroid medication and coded thyroid disorders. Hence, this group caused the highest expenditures. CONCLUSIONS: Given the high prevalence of thyroid disorders, diagnostic and monitoring tests should be used rationally with regard to costs. TSH levels should be monitored regularly in patients on thyroid medication. A consensus on monitoring frequency and iteration of monitoring of morphological thyroid disorders with TSH and ultrasound and specific guideline recommendations are needed. TRIAL REGISTRATION: Versorgungsforschung Deutschland (VfD_17_003880).

Fairness and objectivity of a multiple scenario objective structured clinical examination.

Introduction: The aim of the Objective Structured Clinical Examination (OSCE) is a standardized and fair assessment of clinical skills. Observing second clinical year medical students during a summative OSCE assessing a General Practice clerkship, we noticed that information exchange with peers led to a progressively faster and overly focused management of simulations. Therefore, we established a Multiple Scenario-OSCE (MS-OSCE) where all students had to manage the same chief complaint at a station but it's underlying scenarios being randomly changed during students' rotation through their parcours. We wanted to ensure they fully explore differential diagnosis instead of managing their task influenced by shared information. We wanted to assess if a MS-OSCE violates the assumption of objectivity and fairness given that students are not tested with the same scenarios. Methods: We developed and piloted five OSCE stations (chest pain, abdominal pain, back pain, fatigue and acute cough) with two or three different underlying scenarios each. At each station these scenarios randomly changed from student to student. Performance was assessed with a checklist and global rating. The effect of scenarios and raters on students' grades was assessed calculating the intraclass correlation coefficient with a fixed effect two level linear model. Results: A total of 169 students and 23 raters participated in the MS-OSCE. The internal consistency over all stations was 0.65 by Cronbach's alpha. The difference of the mean grades between the scenarios of a given chief complaint ranged from 0.03 to 0.4 on a 1 to 5 grading scale. The effect of scenarios on the variance of the final grades at each station ranged from 4% to 9% and of raters from 20% to 50% when adjusted for students' skills. Conclusions: The effect of different scenarios on the grades was relevant but small compared to the effect of raters on grades. Improving rater training is more important to ensure objectivity and fairness of MS-OSCE than providing the same scenario to all students.

[Prevalence of thyroid abnormality: a comparison of ambulatory claims data with data from a population-based study]. / Schilddrüsenveränderungen: Ein Vergleich ambulanter Abrechnungsdaten mit Daten einer populationsbasierten Studie.

BACKGROUND: Billing diagnoses are used for quality assurance, estimates of prevalence and resource allocation. Validity studies showed relevant limitations. In Germany, there are no population-based data on the agreement of outpatient billing diagnoses with clinical data of thyroid disorders. OBJECTIVES: The study investigated the agreement of ICD-diagnosed thyroid nodules, goitre, hyperthyroidism, hypothyroidism and thyroiditis with clinical and self-reported data from the population-based cohort study called the Study of Health in Pomerania (SHIP). MATERIALS AND METHODS: Billing data from the Association of Statutory Health Insurance Physicians Mecklenburg-Vorpommern were linked on an individual level for the period from 2002-2016 with data from SHIP. The agreement was evaluated using sensitivity, specificity and positive and negative predictive value (PPW, NPW). Data were weighted to ensure population representativeness. RESULTS: The data of 5746 participants were analysed (46% male, average age 55 years, SD [standard deviation] ± 15, min: 20 years, max: 93 years). Based on clinical data, 63% (3451/5511, missing values n = 235) and based on billing data 25% (1421/5746) of the participants had thyroid disorders. The sensitivity was 12-36%, the specificity was 84-98%, the PPW was highest for thyroid nodules (75%) and hypothyroidism (70%) and the NPW was between 63 and 94%, depending on the investigated thyroid disorder. CONCLUSIONS: Thyroid disorders are common and often undiagnosed. Billing data have a low sensitivity to identify clinically relevant thyroid disorders.

[Prevalence of Cardiovascular Risk Factors at The Population Level: A Comparison of Ambulatory Physician-Coded Claims Data With Clinical Data From A Population-Based Study]. / Untersuchung der Prävalenz kardiologischer Risikofaktoren in der Allgemeinbevölkerung: Ein Vergleich ambulanter ärztlicher Abrechnungsdaten mit Daten einer populationsbasierten Studie.

OBJECTIVE: The study assesses the validity of ICD-10 coded cardiovascular risk factors in claims data using gold-standard measurements from a population-based study for arterial hypertension, diabetes, dyslipidemia, smoking and obesity as a reference. METHODS: Data of 1941 participants (46 % male, mean age 58±13 years) of the Study of Health in Pomerania (SHIP) were linked to electronic medical records from the regional association of statutory health insurance physicians from 2008 to 2012 used for billing purposes. Clinical data from SHIP was used as a gold standard to assess the agreement with claims data for ICD-10 codes I10.- (arterial hypertension), E10.- to E14.- (diabetes mellitus), E78.- (dyslipidemia), F17.- (smoking) and E65.- to E68.- (obesity). RESULTS: A higher agreement between ICD-coded and clinical diagnosis was found for diabetes (sensitivity (sens) 84%, specificity (spec) 95%, positive predictive value (ppv) 80%) and hypertension (sens 72%, spec 93%, ppv 97%) and a low level of agreement for smoking (sens 18%, spec 99%, ppv 89%), obesity (sens 22%, spec 99%, ppv 99%) and dyslipidemia (sens 40%, spec 60%, ppv 70%). Depending on the investigated cardiovascular risk factor, medication, documented additional cardiovascular co-morbidities, age, sex and clinical severity were associated with the ICD-coded cardiovascular risk factor. CONCLUSION: The quality of ICD-coding in ambulatory care is highly variable for different cardiovascular risk factors and outcomes. Diagnoses were generally undercoded, but those relevant for billing were coded more frequently. Our results can be used to quantify errors in population-based estimates of prevalence based on claims data for the investigated cardiovascular risk factors.

Diagnosis and management of non-dialysis chronic kidney disease in ambulatory care: a systematic review of clinical practice guidelines.

BACKGROUND: Chronic kidney disease (CKD) is age-dependent and has a high prevalence in the general population. Most patients are managed in ambulatory care. This systematic review provides an updated overview of quality and content of international clinical practice guidelines for diagnosis and management of non-dialysis CKD relevant to patients in ambulatory care. METHODS: We identified guidelines published from 2012-to March 2018 in guideline portals, databases and by manual search. Methodological quality was assessed with the Appraisal of Guidelines for Research and Evaluation II instrument. Recommendations were extracted and evaluated. RESULTS: Eight hundred fifty-two publications were identified, 9 of which were eligible guidelines. Methodological quality ranged from 34 to 77%, with domains "scope and purpose" and "clarity of presentation" attaining highest and "applicability" lowest scores. Guidelines were similar in recommendations on CKD definition, screening of patients with diabetes and hypertension, blood pressure targets and referral of patients with progressive or stage G4 CKD. Definition of high risk groups and recommended tests in newly diagnosed CKD varied. CONCLUSIONS: Guidelines quality ranged from moderate to high. Guidelines generally agreed on management of patients with high risk or advanced CKD, but varied in regarding the range of recommended measurements, the need for referrals to nephrology, monitoring intervals and comprehensiveness. More research is needed on efficient management of patients with low risk of CKD progression to end stage renal disease.

Quality of care in patients with atrial fibrillation in primary care: a cross-sectional study comparing clinical and claims data.

Objectives: Atrial fibrillation (AF) is a common cardiac arrhythmia with increased risk of thromboembolic stroke. Oral anticoagulation (OAC) reduces stroke risk by up to 68%. The aim of our study was to evaluate quality of care in patients with AF in a primary health care setting with a focus on physician guideline adherence for OAC prescription and heart rate- and rhythm management. In a second step we aimed to compare OAC rates based on primary care data with rates based on claims data. Methods: We included all GP practices in the region Vorpommern-Greifswald, Germany, which were willing to participate (N=29/182, response rate 16%). Claims data was derived from the regional association of statutory health insurance physicians. Patients with a documented AF diagnosis (ICD-10-GM-Code ICD I48.-) from 07/2011-06/2012 were identified using electronic medical records (EMR) and claims data. Stroke and bleeding risk were calculated using the CHA2DS2-VASc and HAS-BLED scores. We calculated crude treatment rates for OAC, rate and rhythm control medications and adjusted OAC treatment rates based on practice and claims data. Adjusted rates were calculated including the CHA2DS2-VASc and HAS-BLED scores and individual factors affecting guideline based treatment. Results: We identified 927 patients based on EMR and 1,247 patients based on claims data. The crude total OAC treatment rate was 69% based on EMR and 61% based on claims data. The adjusted OAC treatment rates were 90% for patients based on EMR and 63% based on claims data. 82% of the AF patients received a treatment for rate control and 12% a treatment for rhythm control. The most common reasons for non-prescription of OAC were an increased risk of falling, dementia and increased bleeding risk. Conclusion: Our results suggest that a high rate of AF patients receive a drug therapy according to guidelines. There is a large difference between crude and adjusted OAC treatment rates. This is due to individual contraindications and comorbidities which cannot be documented using ICD coding. Therefore, quality indicators based on crude EMR data or claims data would lead to a systematic underestimation of the quality of care. A possible overtreatment of low-risk patients cannot be ruled out.

Utility of repeat serum cholesterol measurements for assessment of cardiovascular risk in primary prevention.

BACKGROUND: Measurement of total cholesterol is part of cardiovascular disease risk assessment in primary prevention. Frequently, old total cholesterol values are available. We assessed whether previously measured total cholesterol values could be used to estimate cardiovascular disease risk in primary prevention. DESIGN: A longitudinal analysis using data of a population-based prospective cohort study (Study of Health in Pomerania) over a period of 10 years. METHODS: Altogether, 1112 subjects (45% male, mean age 57.8 years, SD ± 6.8 years) without prior history of myocardial infarction or stroke were included. We calculated diagnostic test properties for SCORE-Germany estimates using 5- and 10-year-old total cholesterol values to predict high (≥5%) cardiovascular disease risk using estimates based on current total cholesterol as a gold standard. RESULTS: Mean total cholesterol decreased from 5.88 mmol/l (SD ± 1.21) at baseline to 5.73 mmol/l (SD ± 1.10) after 10 years. A high cardiovascular disease risk was found in 3.2% of subjects at baseline, in 4.9% after 5 years and in 16.2% after 10 years based on current total cholesterol values. SCORE-estimates using 5-year-old total cholesterol had a sensitivity of 90.9% (95% confidence interval 87.7-94.1) and specificity of 97.2% (95% confidence interval 96.4-98.0). For 10-year-old total cholesterol, sensitivity was 94.2% (95% confidence interval 91.6-96.8) and specificity 96.3% (95% confidence interval 95.3-97.2). CONCLUSIONS: We observed only minor changes of total cholesterol over time. SCORE-estimates using 5- or 10-year-old total cholesterol had a high sensitivity, specificity and test accuracy to identify subjects at high cardiovascular disease risk and resulted in low misclassification rates.

Effects of expiring reimbursability of pentaerythrityl tetranitrate (PETN, pentalong®) on anti-anginal therapy: an observational study.

PURPOSE: Pentaerythrityl tetranitrate (PETN) was the most commonly prescribed long-acting nitrate in Germany. We aimed to assess whether the discontinuation of PETN reimbursability in 2011 resulted in alternative prescriptions of anti-anginal medications or in a discontinuation of anti-anginal therapy. METHODS: This is an observational study using health claims data from one German federal state analysing all patients discontinuing a PETN treatment. Patients starting a new alternative anti-anginal treatment (long-acting nitrates, molsidome, ivabradine and ranolazine) were compared with patients without a new anti-anginal treatment with respect to use of short-acting nitrates, beta blockers (BBs) and calcium channel blockers (CCBs). RESULTS: Out of 12,909 patients, 12,763 (99%) discontinued PETN until 12/2012. Of these, 52% started an alternative anti-anginal treatment, 43% did not receive any alternative treatment and 5% were excluded from analysis. Before termination of PETN reimbursability, 65% of patients received BBs, 29% CCBs and 10% short-acting nitrates. In patients started on alternative anti-anginal treatment, prescription rates for short-acting nitrates, BBs and CCBs remained constant after discontinuing PETN. In patients without any alternative anti-anginal treatment, prescription rates for BBs and CCBs did not change meaningfully (<3%), and prescription rates for short-acting nitrates decreased from 9% to 6%. CONCLUSIONS: Half of the patients discontinued PETN without alternative. This did not lead to increased prescription rates of standard IHD medications or total medication number indicating that there might still be a high percentage of ischaemic heart disease patients treated unnecessarily with long-acting nitrates. The undertreatment with prognostically relevant first-line medications indicates a need for better guideline implementation activities.

Life- and person-centred help in Mecklenburg-Western Pomerania, Germany (DelpHi): study protocol for a randomised controlled trial.

BACKGROUND: The provision of appropriate medical and nursing care for people with dementia is a major challenge for the healthcare system in Germany. New models of healthcare provision need to be developed, tested and implemented on the population level. Trials in which collaborative care for dementia in the primary care setting were studied have demonstrated its effectiveness. These studies have been conducted in different healthcare systems, however, so it is unclear whether these results extend to the specific context of the German healthcare system.The objective of this population-based intervention trial in the primary care setting is to test the efficacy and efficiency of implementing a subsidiary support system on a population level for persons with dementia who live at home. METHODS AND STUDY DESIGN: The study was designed to assemble a general physician-based epidemiological cohort of people above the age of 70 who live at home (DelpHi cohort). These people are screened for eligibility to participate in a trial of dementia care management (DelpHi trial). The trial is a cluster-randomised, controlled intervention trial with two arms (intervention and control) designed to test the efficacy and efficiency of implementing a subsidiary support system for persons with dementia who live at home. This subsidiary support system is initiated and coordinated by a dementia care manager: a nurse with dementia-specific qualifications who delivers the intervention according to a systematic, detailed protocol. The primary outcome is quality of life and healthcare for patients with dementia and their caregivers. This is a multidimensional outcome with a focus on four dimensions: (1) quality of life, (2) caregiver burden, (3) behavioural and psychological symptoms of dementia and (4) pharmacotherapy with an antidementia drug and prevention or suspension of potentially inappropriate medication. Secondary outcomes include the assessment of dementia syndromes, activities of daily living, social support health status, utilisation of health care resources and medication. DISCUSSION: The results will provide evidence for specific needs in ambulatory care for persons with dementia and will show effective ways to meet those needs. Qualification requirements will be evaluated, and the results will help to modify existing guidelines and treatment paths. TRIAL REGISTRATION: NCT01401582.

The use and impact of national confidential enquiries in high-income countries.

OBJECTIVE: To describe the use and characteristics of national confidential enquiries (NCEs) into adverse outcomes of healthcare in high-income countries and to review the evidence of their impact. METHOD: Systematic search of bibliometric databases plus review of cited references and search of websites. Eleven characteristics of NCEs were extracted. Studies evaluating the impact of three NCEs were searched for. Data were extracted and tabulated, and a narrative review conducted. RESULTS: Establishment of NCEs has been limited with only 27 examples identified in over 50 years and only nine currently functioning. They have been particularly popular in the nations of the UK (17 of the 27) and in services around childbirth (15/27). NCEs mostly include all cases (19/23) and include adverse outcomes both during and after the initial hospital episode (17/23). The annual volume of cases varies from four to over 6000. With one exception, NCEs make no attempt to use 'controls.' Research evidence of the impact of the recommendations from three of the largest and longest running NCEs is poor, with no time-series analyses or experimental studies, and is restricted to considering their impact on the structure and process rather than the outcome of care. CONCLUSIONS: The lack of scientific evidence on the impact of NCEs on improving safety, combined with uncertainty as to the validity of their recommendations and their high cost, suggests the need for rigorous evaluation and a reconsideration of their contribution. One option is to nest NCEs within prospective national clinical audits.

Effects of immunoadsorption and subsequent immunoglobulin G substitution on cardiopulmonary exercise capacity in patients with dilated cardiomyopathy.

BACKGROUND: Recent data indicate that cardiac antibodies play an active role in the pathogenesis of dilated cardiomyopathy (DCM) and may contribute to cardiac dysfunction in patients with DCM. The present study investigated the influence of immunoadsorption with subsequent immunoglobulin G substitution (IA/IgG) on cardiopulmonary exercise capacity in patients with DCM. METHODS: Sixty patients with DCM (New York Heart Association II-IV, left ventricular ejection fraction < or =45%) were included in this single-center university hospital-based case-control study. Patients either were treated with IA/IgG (n = 30) or were followed without IA/IgG (n = 30). At baseline and after 3 months, we compared echocardiographic assessment of left ventricular function and spiroergometric exercise parameters. RESULTS: In contrast to controls, left ventricular ejection fraction improved significantly in the IA/IgG group from 33.0% +/- 1.2% to 40.1% +/- 1.5% (P < .001). In the control group, spiroergometric exercise parameters did not change during follow-up. After 3 months, maximum achieved power increased in the treatment group from 114.2 +/- 7.4 to 141.9 +/- 7.9 W (P = .02). Total exercise time increased in the treatment group from 812 +/- 29 to 919 +/- 30 seconds (P < .05). Peak oxygen uptake (Vo(2)) increased from 17.3 +/- 0.9 to 21.8 +/- 1.0 mL min(-1) kg(-1) after IA/IgG (P < .01). Oxygen pulse (peak Vo(2)/maximum heart rate) increased in the treatment group (10.7 +/- 0.7 vs 13.6 +/- 0.7 mL beat(-1) min(-1), P < .01). The Vo(2) at the gas exchange anaerobic threshold increased after 3 months in the treatment group from 10.3 +/- 0.5 to 13.2 +/- 0.5 mL min(-1) kg(-1) (P < .001). The ventilatory response to exercise (V(E)/Vco(2) slope) decreased after IA/IgG therapy from 32.3 +/- 1.5 to 28.7 +/- 0.9 (P = .02). CONCLUSIONS: In patients with DCM, IA/IgG therapy may induce improvement in echocardiographic and cardiopulmonary exercise parameters.

Methods and implementation of a central biosample and data management in a three-centre clinical study.

In our report we describe concept, strategies and implementation of a central biosample and data management (CSDM) system in the three-centre clinical study of the Transregional Collaborative Research Centre "Inflammatory Cardiomyopathy - Molecular Pathogenesis and Therapy" SFB/TR 19, Germany. Following the requirements of high system resource availability, data security, privacy protection and quality assurance, a web-based CSDM was developed based on Java 2 Enterprise Edition using an Oracle database. An efficient and reliable sample documentation system using bar code labelling, a partitioning storage algorithm and an online documentation software was implemented. An online electronic case report form is used to acquire patient-related data. Strict rules for access to the online applications and secure connections are used to account for privacy protection and data security. Challenges for the implementation of the CSDM resided at project, technical and organisational level as well as at staff level.

Towards risk factor assessment in inflammatory dilated cardiomyopathy: the SFB/TR 19 study.

BACKGROUND: Patients with idiopathic dilated cardiomyopathy (DCMid) account for about one-third of patients with heart failure. Recent studies found a myocardial viral genomic persistence in up to 67% of DCMid patients, indicating a possible inflammatory etiology (DCMi). Considering the importance of DCMi, we aimed to study the present knowledge on risk factors in DCMi. METHODS: Review of published literature on risk factors for DCMi/DCMid from 1989 through 2005 in Medline database and the Cochrane library (search terms 'epidemiology', 'risk factors', 'inflammatory dilated cardiomyopathy' and 'idiopathic dilated cardiomyopathy'). RESULTS: An extended array of risk factors in DCMid has been investigated in 11 studies. No studies addressing specifically DCMi, however, were found. Consistent associations with DCMid were reported only for diabetes mellitus, black race, male sex and estimated low income. Inconsistent results were observed for the presence of asthma, hypertension and smoking. Few studies addressed potential risk factors such as low education level, infectious diseases and environmental factors. CONCLUSIONS: Considering the high number of potential DCMi patients among patients with DCMid, results on risk factors for DCMid are likely relevant to at least a number of patients with DCMi. Future studies of risk factors in DCMi should include specific case classification and the application of standardized instruments for risk-factor assessment. The four-center SFB/TR 19 study aims to establish a prospective cohort of DCMi patients validated by endomyocardial biopsy.