Machine Learning Models Predict the Need of Amputation and/or Peripheral Artery Revascularization in Hypertensive Patients Within 7-Years Follow-Up.

Lower extremity amputation and requirement of peripheral artery revascularization are common outcomes of undiagnosed peripheral artery disease patients. In the current work, prediction models for the need of amputation or peripheral revascularization focused on hypertensive patients within seven years follow up are employed. We applied machine learning (ML) models using classifiers such as Extreme Gradient Boost (XGBoost), Random Forest (RF) and Adaptive Boost (AdaBoost), that will allow clinicians to identify the patients at risk of these two endpoints using simple clinical data. We used the non-interventional cohort of the getABI study in the primary care setting, selecting 4,191 hypertensive patients out of 6,474 patients with age over 65 years old and followed up for vascular events or death up to 7 years. During this follow up period, 150 patients underwent either amputation or peripheral revascularization or both. Accuracy, Specificity, Sensitivity and Area under the receiver operating characteristic curve (AUC) were estimated for each machine learning model. The results demonstrate Random Forest as the most accurate model for the prediction of the composite endpoint in hypertensive patients within 7 years follow-up, achieving 73.27 % accuracy.Clinical Relevance-This study assists clinicians to better predict and treat these serious outcomes, amputation and peripheral revascularization in hypertensive patients.

The Efficacy of Short-Term Bridging Strategies With High- and Low-Dose Prednisolone on Radiographic and Clinical Outcomes in Active Early Rheumatoid Arthritis: A Double-Blind, Randomized, Placebo-Controlled Trial.

OBJECTIVE: In active early rheumatoid arthritis (RA), glucocorticoids are often used for bridging, due to the delayed action of methotrexate. This study was undertaken to compare the effect of 3 bridging strategies, including high-dose and low-dose prednisolone, on radiographic and clinical outcomes. METHODS: Adult RA patients from 1 rheumatology hospital and 23 rheumatology practices who presented with moderate/high disease activity were randomized (1:1:1) to receive 60 mg prednisolone (high-dose prednisolone [HDP]) or 10 mg prednisolone (low-dose prednisolone [LDP]) daily (tapered to 0 mg within 12 weeks) or placebo. The 12-week intervention period was followed by 40 weeks of therapy at the physicians' discretion. The primary outcome measure was radiographic change at 1 year measured using the total modified Sharp/van der Heijde score (SHS). Disease activity was assessed with the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR). RESULTS: Of 395 randomized patients (HDP, n = 132; LDP, n = 131; placebo, n = 132), 375 (95%) remained in the modified intention-to-treat analysis. Mean ± SD changes in SHS scores in the 3 groups after 1 year were comparable: mean ± SD 1.0 ± 2.0 units in the HDP group, 1.1 ± 2.2 units in the LDP group, and 1.1 ± 1.5 units in the placebo group. The primary analysis showed no superiority of HDP compared to placebo (estimated difference of the mean change -0.04 [95% confidence interval (95% CI) -0.5, 0.4]). At week 12, the mean DAS28-ESR differed: -0.6 (95% CI -1.0, -0.2) for HDP versus placebo; -0.8 (95% CI -1.2, -0.5) for LDP versus placebo. At week 52, there was no significant difference in DAS28-ESR between the 3 groups (range 2.6-2.8). Serious adverse events occurred similarly often. CONCLUSION: Short-term glucocorticoid bridging therapy at a high dose showed no benefit with regard to progression of radiographic damage at 1 year.

The Structured Delegation of Medical Care Services for Patients With Inflammatory Rheumatic Diseases.

BACKGROUND: In some areas of Germany, there is a shortage of specialist physicians for patients with inflammatory rheumatic diseases. Delegating certain medical care services to qualified, specialized rheumatological assistants (SRAs) might be an effective way to supplement the available capacity for specialized medical care. METHODS: Patients under stable treatment for rheumatoid arthritis (RA) or psoriatic arthritis (PsA) were included in this trial, which was designed to demonstrate, in a first step, the non-inferiority of a form of care involving delegation of physicians' tasks to SRAs (team-based care), in comparison to standard care, with respect to changes in disease activity at one year. "Non-inferiority," in this context, means either superiority or else an irrelevant extent of inferiority. In a second step, in case non-inferiority could be shown, the superiority of team-based care with respect to changes in patients' health-related quality of life would be tested as well. Disease activity was measured with the Disease Activity Score 28, and health-related quality of life with the EQ-5D-5L. This was a randomized, multicenter, rater-blinded trial with two treatment arms (team-based care and standard care). The statistical analysis was performed with mixed linear models (DRKS00015526). RESULTS: From September 2018 to June 2019, 601 patients from 14 rheumatological practices and 3 outpatient rheumatological clinics in the German states of North Rhine-Westphalia and Lower Saxony were randomized to either team-based or standard care. Team-based care was found to be non-inferior to standard care with respect to changes in disease activity (adjusted difference = -0.19; 95% confidence interval [-0.36; -0.02]; p <0.001 for non-inferiority). Superiority with respect to health-related quality of life was not demonstrated (adjusted difference = 0.02 [-0.02; 0.05], p = 0.285). CONCLUSION: Team-based care, with greater integration of SRAs, is just as good as standard care in important respects. Trained SRAs can effectively support rheumatologists in the care of stable patients with RA or PsA.

Effects of Three Different Methods Defining Onset of Peripheral Artery Disease on the Assessments of Incidence and Important Predictors - Results from the German Epidemiological Trial on Ankle Brachial Index (getABI).

PURPOSE: The common definition of asymptomatic peripheral artery disease (PAD) by a single determination of the ankle brachial index (ABI) has some uncertainty due to measurement errors. This may impact estimates of PAD incidence and assessment of PAD risk factors. To investigate this issue, we used three methods to define asymptomatic PAD and made use of data from the German Epidemiological Trial on Ankle Brachial Index (getABI). PATIENTS AND METHODS: A total of 6,880 unselected subjects aged ≥65 years, enrolled by 344 trained general practitioners, had ABI assessments at baseline and four visits during follow-up. The first approach defined asymptomatic PAD onset as soon as a single ABI value was below 0.9 (single ABI). The second approach employed a regression method using all available ABI values (regression A), while for the third approach (regression B), an extended regression beyond the last valid ABI value for the observation time of the study was allowed. For each approach, we calculated PAD incidence rates and assessed the effect of important PAD predictors using multivariable Cox proportional hazards regression. RESULTS: The regression method A showed the lowest (25.0 events per 1,000 person years) and the single ABI method the highest incidence rate (41.2). The regression methods assigned greater impact to several risk factors of incident PAD. Using regression A, the hazard ratios (HR) of active smoking (2.36; 95% CI 1.92 to 2.90) and of diabetes (1.33; 95% CI 1.13 to 1.56), using regression B the HR of older age (1.72; 95% CI 1.50 to 1.97) were about twice as high as the corresponding HR of the single ABI approach. CONCLUSION: Use of the single ABI method leads to higher PAD incidence rates and to lower impact of important PAD predictors compared to regression methods. For an alert risk factor management, multiple ABI determination may be useful.

Reduction of Potentially Inappropriate Medication in the Elderly.

BACKGROUND: Medications with an unfavorable risk-benefit profile in the elderly, and for which there are safer alternatives, are designated as potentially inappropriate medications (PIM). The RIME trial (Reduction of Potentially Inappropriate Medication in the Elderly) was based on PRISCUS, a list of PIM that was developed in 2010 for the German pharmaceuticals market. In this trial, it was studied whether special training and the PRISCUS card could lessen PIM and undesired drug-drug interactions (DDI) among elderly patients in primary care. METHODS: A three-armed, cluster-randomized, controlled trial was carried out in two regions of Germany. 137 primary care practices were randomized in equal numbers to one of two intervention groups-in which either the primary care physicians alone or the entire practice team received special training-or to a control group with general instructions about medication. The primary endpoint was the percentage of patients with at least one PIM or DDI (PIM/DDI) per practice. The primary hypothesis was that at 1 year this endpoint would be more effectively lowered in the intervention groups compared to the control group. RESULTS: Among 1138 patients regularly taking more than five drugs, 453 (39.8%) had at least one PIM/DDI at the beginning of the trial. The percent - ages of PIM/DDI at the beginning of the trial and 1 year later were 43.0% and 41.3% in the intervention groups and 37.0% and 37.6% in the control group. The estimated intervention effect of any intervention (69 practices) versus control (68 practices) was 2.3% (p = 0.36), while that of team training (35 practices) versus physician training (34 practices) was 4.3% (p = 0.22). CONCLUSION: The interventions in the RIME trial did not significantly lower the percentage of patients with PIM or DDI.

Predicting hospital admissions from individual patient data (IPD): an applied example to explore key elements driving external validity.

OBJECTIVE: To explore factors that potentially impact external validation performance while developing and validating a prognostic model for hospital admissions (HAs) in complex older general practice patients. STUDY DESIGN AND SETTING: Using individual participant data from four cluster-randomised trials conducted in the Netherlands and Germany, we used logistic regression to develop a prognostic model to predict all-cause HAs within a 6-month follow-up period. A stratified intercept was used to account for heterogeneity in baseline risk between the studies. The model was validated both internally and by using internal-external cross-validation (IECV). RESULTS: Prior HAs, physical components of the health-related quality of life comorbidity index, and medication-related variables were used in the final model. While achieving moderate discriminatory performance, internal bootstrap validation revealed a pronounced risk of overfitting. The results of the IECV, in which calibration was highly variable even after accounting for between-study heterogeneity, agreed with this finding. Heterogeneity was equally reflected in differing baseline risk, predictor effects and absolute risk predictions. CONCLUSIONS: Predictor effect heterogeneity and differing baseline risk can explain the limited external performance of HA prediction models. With such drivers known, model adjustments in external validation settings (eg, intercept recalibration, complete updating) can be applied more purposefully. TRIAL REGISTRATION NUMBER: PROSPERO id: CRD42018088129.

Effectiveness of the application of an electronic medication management support system in patients with polypharmacy in general practice: a study protocol of cluster-randomised controlled trial (AdAM).

INTRODUCTION: Clinically complex patients often require multiple medications. Polypharmacy is associated with inappropriate prescriptions, which may lead to negative outcomes. Few effective tools are available to help physicians optimise patient medication. This study assesses whether an electronic medication management support system (eMMa) reduces hospitalisation and mortality and improves prescription quality/safety in patients with polypharmacy. METHODS AND ANALYSIS: Planned design: pragmatic, parallel cluster-randomised controlled trial; general practices as randomisation unit; patients as analysis unit. As practice recruitment was poor, we included additional data to our primary endpoint analysis for practices and quarters from October 2017 to March 2021. Since randomisation was performed in waves, final study design corresponds to a stepped-wedge design with open cohort and step-length of one quarter. SCOPE: general practices, Westphalia-Lippe (Germany), caring for BARMER health fund-covered patients. POPULATION: patients (≥18 years) with polypharmacy (≥5 prescriptions). SAMPLE SIZE: initially, 32 patients from each of 539 practices were required for each study arm (17 200 patients/arm), but only 688 practices were randomised after 2 years of recruitment. Design change ensures that 80% power is nonetheless achieved. INTERVENTION: complex intervention eMMa. FOLLOW-UP: at least five quarters/cluster (practice). recruitment: practices recruited/randomised at different times; after follow-up, control group practices may access eMMa. OUTCOMES: primary endpoint is all-cause mortality and hospitalisation; secondary endpoints are number of potentially inappropriate medications, cause-specific hospitalisation preceded by high-risk prescribing and medication underuse. STATISTICAL ANALYSIS: primary and secondary outcomes are measured quarterly at patient level. A generalised linear mixed-effect model and repeated patient measurements are used to consider patient clusters within practices. Time and intervention group are considered fixed factors; variation between practices and patients is fitted as random effects. Intention-to-treat principle is used to analyse primary and key secondary endpoints. ETHICS AND DISSEMINATION: Trial approved by Ethics Commission of North-Rhine Medical Association. Results will be disseminated through workshops, peer-reviewed publications, local and international conferences. TRIAL REGISTRATION: NCT03430336. ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT03430336).

Bisphosphonate drug holidays: Risk of fractures and mortality in a prospective cohort study.

PURPOSE: This study examined osteoporotic fractures and mortality in patients pretreated with bisphosphonates (BPs) during BP holidays and ongoing BP use. METHODS: Interview-based prospective observational study in a cohort of 1973 patients with BP treatment for at least 80% of the total time of the preceding 4 years. Patients were recruited from 146 primarily endocrinological, orthopedic and rheumatological practices and clinics across Germany between May 2013 and June 2015. Outcomes were analyzed by Cox proportional hazards regression in relation to treatment status at the time of the first interview (model 1) or using time-dependent treatment variables (model 2). Temporal changes in fracture risk during BP holidays were evaluated by comparisons among 3 incremental levels of simple moving averages of BP treatment during the preceding 12 months (BP-SMA levels 0%, >0% to <50%, and ≥50%). RESULTS: For an observation period of up to 25 months, the adjusted hazard ratios (HRs) in model 1 for BP holidays compared to ongoing BP use were 0.87 (95% confidence interval [CI] 0.59-1.28) for major osteoporotic fractures (MOFs), 0.95 (95% CI 0.70-1.28) for any clinical osteoporotic fracture, 0.96 (95% CI 0.55-1.68) for clinical vertebral fractures, and 0.86 (95% CI 0.50-1.48) for mortality. The risk of MOFs was higher for the BP-SMA level 0%, corresponding to a time >12 months since the start of a BP holiday, than for the BP-SMA level >0% to <50%, corresponding mainly to a time >6 to ≤12 months since the start of a BP holiday (adjusted HR 2.28, 95% CI 1.07-4.86). We found an interaction between prevalent vertebral fractures (PVFs) and BP-SMA-related time to first MOF for BP-SMA as a continuous variable (p for interaction 0.046 in the adjusted model). The adjusted HR for MOFs for the BP-SMA level 0% compared to the BP-SMA level >0% to <50% was 3.53 (95% CI 1.19-10.51) with a PVF but was 1.44 (95% CI 0.49-4.22) without a PVF. CONCLUSIONS: Fracture risk and mortality in patients with preceding BP treatment did not significantly differ between BP holidays and ongoing BP use for an observation period up to 25 months when outcomes were analyzed in relation to treatment at the time of the first interview. However, in the presence of a PVF, the risk of MOFs was higher for a BP-SMA level corresponding to a time >12 months since the start of a BP holiday than for a BP-SMA level corresponding mainly to a time >6 to ≤12 months since the start of a BP holiday. The presence of a PVF may increase the relative risk of MOFs associated with a longer BP holiday.

NT-proBNP for risk prediction of cardiovascular events and all-cause mortality: The getABI-study.

BACKGROUND: Beside their role in the diagnosis of heart failure in symptomatic patients with dyspnea, natriuretic peptides have been suggested to improve risk prediction of cardiac events and mortality in asymptomatic cohorts. We aimed to evaluate the prognostic value of NT-proBNP for cardiovascular and all-cause mortality above traditional risk factors in a prospective cohort study of unselected elderly patients in a representative primary care setting. METHODS: We followed 6382 patients of the getABI-study for 7 years. Associations of NT-proBNP levels (≤125; 125-300; >300pg/ml for all) with all-cause and cardiovascular mortality were assessed using cox regression analysis. RESULTS: The incidence of all-cause and cardiovascular mortality was higher in subjects with higher levels of NT-proBNP (all-cause mortality/cardiovascular mortality: 35.4%/6% for NT-proBNP > 300 pg/ml; 16.2%/40% for NT-proBNP 125-300 pg/ml vs. 11.4%/4% for NT-proBNP ≤ 125 pg/ml. Participants with a NT-proBNP levels > 300pg/ml had increased incidence of hard endpoint (hazard ratio (HR) (95% confidence interval (CI)): 3.62 (3.15-4.17) for all-cause mortality, and 6.38 (4.84-8.41) for cardiovascular mortality). These associations remained after adjustment for traditional risk factors and cardiac medications and diseases (HR = 2.64 (2.26-3.08) for all-cause mortality, and HR = 3.93 (2.90-5.32) for cardiovascular mortality). CONCLUSION: Our results show strong associations of higher NT-proBNP levels with cardiovascular and all-cause mortality in an unselected, large population of elderly patients in the primary care setting independent of traditional risk factors indicating that NT-proBNP can help identifying subjects at high risk for cardiac events.

Nurse-led care versus physician-led care in the management of rheumatoid arthritis and psoriatic arthritis (StaerkeR): study protocol for a multi-center randomized controlled trial.

BACKGROUND: In Germany, the care of patients with inflammatory arthritis could be improved. Although specialized rheumatology nurses could take over substantial aspects of patient care, this hardly occurs in Germany. Thus, the aim of the study is to examine structured nursing consultation in rheumatology practices. METHODS/DESIGN: In total, 800 patients with a stable course of rheumatoid arthritis or psoriatic arthritis in 20 centers in North Rhine-Westphalia and Lower Saxony will be randomized to either nurse-led care or standard care. Participating nurses will study for a special qualification in rheumatology and trial-specific issues. It is hypothesized that nurse-led care is non-inferior to standard care provided by rheumatologists with regard to a reduction of disease activity (DAS28) while it is hypothesized to be superior regarding changes in health-related quality of life (EQ-5D-5L) after 1 year. Secondary outcomes include functional capacity, patient satisfaction with treatment, and resource consumption. DISCUSSION: Since there is insufficient care of rheumatology patients in Germany, the study may be able to suggest improvements. Nurse-led care has the potential to provide more efficient and effective patient care. This includes a more stringent implementation of the treat-to-target concept, which may lead to a higher percentage of patients reaching their treatment targets, thereby improving patient-related outcomes, such as quality of life, functional capacity, and participation. Additionally, nurse-led care may be highly cost-effective. Finally, this project may form the basis for a sustainable implementation of nurse-led care in standard rheumatology care in Germany. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00015526. Registered on 11 January 2019.

German Acupuncture Trials (GERAC) for chronic low back pain: randomized, multicenter, blinded, parallel-group trial with 3 groups.

BACKGROUND: To our knowledge, verum acupuncture has never been directly compared with sham acupuncture and guideline-based conventional therapy in patients with chronic low back pain. METHODS: A patient- and observer-blinded randomized controlled trial conducted in Germany involving 340 outpatient practices, including 1162 patients aged 18 to 86 years (mean +/- SD age, 50 +/- 15 years) with a history of chronic low back pain for a mean of 8 years. Patients underwent ten 30-minute sessions, generally 2 sessions per week, of verum acupuncture (n = 387) according to principles of traditional Chinese medicine; sham acupuncture (n = 387) consisting of superficial needling at nonacupuncture points; or conventional therapy, a combination of drugs, physical therapy, and exercise (n = 388). Five additional sessions were offered to patients who had a partial response to treatment (10%-50% reduction in pain intensity). Primary outcome was response after 6 months, defined as 33% improvement or better on 3 pain-related items on the Von Korff Chronic Pain Grade Scale questionnaire or 12% improvement or better on the back-specific Hanover Functional Ability Questionnaire. Patients who were unblinded or had recourse to other than permitted concomitant therapies during follow-up were classified as nonresponders regardless of symptom improvement. RESULTS: At 6 months, response rate was 47.6% in the verum acupuncture group, 44.2% in the sham acupuncture group, and 27.4% in the conventional therapy group. Differences among groups were as follows: verum vs sham, 3.4% (95% confidence interval, -3.7% to 10.3%; P = .39); verum vs conventional therapy, 20.2% (95% confidence interval, 13.4% to 26.7%; P < .001); and sham vs conventional therapy, 16.8% (95% confidence interval, 10.1% to 23.4%; P < .001. CONCLUSIONS: Low back pain improved after acupuncture treatment for at least 6 months. Effectiveness of acupuncture, either verum or sham, was almost twice that of conventional therapy.

The effect of time-to-surgery on outcome in elderly patients with proximal femoral fractures.

BACKGROUND: Whether reducing time-to-surgery for elderly patients suffering from hip fracture results in better outcomes remains subject to controversial debates. METHODS: As part of a prospective observational study conducted between January 2002 and September 2003 on hip-fracture patients from 268 acute-care hospitals all over Germany, we investigated the relationship of time-to-surgery with frequency of post-operative complications and one-year mortality in elderly patients (age > or =65) with isolated proximal femoral fracture (femoral neck fracture or pertrochanteric femoral fracture). Patients with short (< or =12 h), medium (> 12 h to < or =36 h) and long (> 36 h) times-to-surgery, counting from the time of the fracture event, were compared for patient characteristics, operative procedures, post-operative complications and one-year mortality. RESULTS: Hospital data were available for 2916 hip-fracture patients (mean age (SD) in years: 82.1 (7.4), median age: 82; 79.7% women). Comparison of groups with short (n = 802), medium (n = 1191) and long (n = 923) time-to-surgery revealed statistically significant differences in a few patient characteristics (age, American Society of Anesthesiologists ratings classification and type of admission) and in operative procedures (total hip endoprosthesis, hemi-endoprosthetic implants, other osteosynthetic procedures). However, comparison of these same groups for frequency of postoperative complications revealed only some non-significant associations with certain complications such as post-operative bleeding requiring treatment (early surgery patients) and urinary tract infections (delayed surgery patients). Both unadjusted rates of one-year all-cause mortality (between 18.1% and 20.5%), and the multivariate-adjusted hazard ratios (HR for time-to-surgery: 1.04; p = 0.55) showed no association between mortality and time-to-surgery. CONCLUSION: Although this study found a trend toward more frequent post-operative complications in the longest time-to-surgery group, there was no effect of time-to-surgery on mortality. Shorter time-to-surgery may be associated with somewhat lower rates of post-operative complications such as decubitus ulcers, urinary tract infections, thromboses, pneumonia and cardiovascular events, and with somewhat higher rates of others such as post-operative bleeding or implant complications.

Social Gradients in Myocardial Infarction and Stroke Diagnoses in Emergency Medicine.

BACKGROUND: Persons of lower socio-economic status are at higher risk of disease, especially with respect to severe and chronic illnesses. To date, there have not been any studies with large case numbers regarding acute medical emergencies in this population. METHODS: In a retrospective study, data were obtained on all cases treated by emergency physicians in Bochum, Germany, in 2014/2015, including the diagnoses that were made by the emergency physicians. There were a total of 16 767 cases. The local unemployment rate was taken as an indicator of the socioeconomic situation of a neighborhood; it was defined as the percentage of registered unemployed persons among persons aged 15 to 64 with their domicile in the neighborhood. 12 168 cases were grouped by emergency medical diagnosis and analyzed with respect to the three most heavily represented diagnostic categories (cardiovascular, neurological, and pulmonary emergencies), which accounted for nearly two-thirds of all diagnoses. RESULTS: The overall rates of deployment involving emergency physicians were found to be positively correlated with the unemployment rate. After adjustment for age, sex, and possible confounders, this correlation was statistically significant (p<0.01). The indirectly standardized rate ratio (IRR) for the overall case-activity rate ranged from 0.841 (95% confidence interval: [0.808; 0.875]) with less than 5% unemployment to 1.212 [1.168; 1.256] with 9.5% unemployment or higher. The same finding was obtained with respect to diagnosis-specific case activity in each of the three main diagnostic categories (cardiovascular, neurological, and pulmonary emergencies), as well as for the respective commonest individual diagnoses (acute coronary syndrome/circulatory arrest [1498 cases], transient ischemic attack/ischemic stroke/intracerebral hemorrhage [1274 cases], and asthma/chronic obstructive pulmonary disease [663 cases]). CONCLUSION: This study shows that the case-activity rate of the emergency medical services is significantly higher in socially disadvantaged neighborhoods, both with respect to total numbers and with respect to individual diseases. It demonstrates a problem affecting society as a whole, which should be taken into account in the organization of medical rescue services.

Randomised controlled comparison of the Health Survey Short Form (SF-12) and the Graded Chronic Pain Scale (GCPS) in telephone interviews versus self-administered questionnaires. Are the results equivalent?

BACKGROUND: The most commonly used survey methods are self-administered questionnaires, telephone interviews, and a mixture of both. But until now evidence out of randomised controlled trials as to whether patient responses differ depending on the survey mode is lacking. Therefore this study assessed whether patient responses to surveys depend on the mode of survey administration. The comparison was between mailed, self-administered questionnaires and telephone interviews. METHODS: A four-armed, randomised controlled two-period change-over design. Each patient responded to the same survey twice, once in written form and once by telephone interview, separated by at least a fortnight. The study was conducted in 2003/2004 in Germany. 1087 patients taking part in the German Acupuncture Trials (GERAC cohort study), who agreed to participate in a survey after completing acupuncture treatment from an acupuncture-certified family physician for headache, were randomised. Of these, 823 (664 women) from the ages of 18 to 83 (mean 51.7) completed both parts of the study. The main outcome measure was the comparison of the scores on the 12-Item Short-Form Health Survey (SF-12) and the Graded Chronic Pain Scale (GCPS) questionnaire for the two survey modes. RESULTS: Computer-aided telephone interviews (CATI) resulted in significantly fewer missing data (0.5%) than did mailed questionnaires (2.8%; p < 0.001). The analysis of equivalence revealed a difference between the survey modes only for the SF-12 mental scales. On average, reported mental status score was 3.5 score points (2.9 to 4.0) lower on the self-administered questionnaire compared to the telephone interview. The order of administration affected results. Patients who responded to the telephone interview first reported better mental health in the subsequent paper questionnaire (mean difference 2.8 score points) compared to those who responded to the paper questionnaire first (mean difference 4.1 score points). CONCLUSION: Despite the comparatively high cost of telephone interviews, they offer clear advantages over mailed self-administered questionnaires as regards completeness of data. Only items concerning mental status were dependent on the survey mode and sequence of administration. Items on physical status were not affected. Normative data for standardized telephone questionnaires could contribute to a better comparability with the results of the corresponding standardized paper questionnaires.

Herbal medicinal products - Evidence and tradition from a historical perspective.

BACKGROUND: Aside from the fully licensed herbal medicines there are products on the European pharmaceutical market which are registered by virtue of their longstanding traditional use. The normal registration procedure does not apply to them because presently they do not meet the legal requirements for a full license as set out in the relevant European Union Directive. One of these requirements, "proof of tradition", has so far been dealt with in different ways and fails to meet the criteria of good practice. METHOD: This analysis is based on a selective literature search in PubMed and in databases of medical and pharmaceutical history, interviews with licensing experts, a consensus meeting attended by researchers with a background in general medicine, phytotherapy, medical and pharmaceutical history, biometry, ethnopharmacology, pharmacognosy and the pharmaceutical industry. RESULTS AND DISCUSSION: The 2004 EU Directive, which governs the registration of Traditional Herbal Medicinal Products and demands proof of tradition, is a regulatory construct and, above all, the outcome of a political process that has ended in a pragmatic compromise. The concept of tradition applied in the Directive does not sufficiently reflect the semantic breadth of the term. The only condition defined is that a specific commercial preparation needs to have been on the market for 30 years (15 of them inside the EU). Such an approach does not make full scientific use of the evidence available because the information excerpted from historical sources, if adequately processed, may yield valuable insights. This applies to indications, modes of application, efficacy and product safety (innocuousness). Such criteria should enter in full into the benefit-risk-analysis of applied preparations, in the registration process as well as in the therapeutic practice. CONCLUSION: When registering Traditional Herbal Medicinal Products the criterion of evidence-based medicine will only be met if all the facts available are assessed and evaluated, over and above the formally stipulated regulatory provisions (30 years, product reference). To this end, the scientific methods (from among the natural, life or cultural sciences), which are recognized as authoritative in each case, must be applied.

Patients with femoral or distal forearm fracture in Germany: a prospective observational study on health care situation and outcome.

BACKGROUND: Distal radius and proximal femoral fractures are typical injuries in later life, predominantly due to simple falls, but modulated by other relevant factors such as osteoporosis. Fracture incidence rates rise with age. Because of the growing proportion of elderly people in Western industrialized societies, the number of these fractures can be expected to increase further in the coming years, and with it the burden on healthcare resources. Our study therefore assessed the effects of these injuries on the health status of older people over time. The purpose of this paper is to describe the study method, clinical parameters of fracture patients during hospitalization, mortality up to one and a half years after discharge in relation to various factors such as type of fracture, and to describe changes in mobility and living situation. METHODS: Data were collected from all consecutive patients (no age limit) admitted to 423 hospitals throughout Germany with distal radius or femoral fractures (57% acute-care, femoral and forearm fractures; 43% rehabilitation, femoral fractures only) between January 2002 and September 2003. Polytrauma and coma patients were excluded. Demographic characteristics, exact fracture location, mobility and living situation, clinical and laboratory parameters were examined. Current health status was assessed in telephone interviews conducted on average 6-7 months after discharge. Where telephone contact could not be established, at least survival status (living/deceased/date of death) was determined. RESULTS: The study population consisted of 12,520 femoral fracture patients (86.8% hip fractures), average age 77.5 years, 76.5% female, and 2,031 forearm fracture patients, average age 67.6 years, 81.6% female. Women's average age was 6.6 (femoral fracture) to 10 years (forearm fracture) older than men's (p < 0.0001). Only 4.6% of femoral fracture patients experienced changes in their living situation post-discharge (53% because of the fracture event), although less than half of subjects who were able to walk without assistive devices prior to the fracture event (76.7%) could still do so at time of interview (34.9%). At time of interview, 1.5% of subjects were bed-ridden (0.2% before fracture). Forearm fracture patients reported no change in living situation at all. Of the femoral fracture patients 119 (0.95%), and of the forearm fracture patients 3 (0.15%) died during hospital stay. Post-discharge (follow-up one and a half years) 1,463 femoral fracture patients died (19.2% acute-care patients, 8.5% rehabilitation patients), but only 60 forearm fracture patients (3.0%). Ninety percent of femoral fracture deaths happened within the first year, approximately 66% within the first 6 months. More acute-care patients with a pertrochanteric fracture died within one year post-discharge (20.6%) than patients with a cervical fracture (16.1%). CONCLUSION: Mortality after proximal femoral fracture is still alarmingly high and highest after pertrochanteric fracture. Although at time of interview more than half of femoral fracture patients reported reduced mobility, most patients (96%) attempt to live at home. Since forearm fracture patients were on average 10 years younger than femoral fracture patients, forearm fractures may be a means of diagnosing an increased risk of later hip fractures.

Comparison of the efficacy and safety of two starting dosages of prednisolone in early active rheumatoid arthritis (CORRA): study protocol for a randomized controlled trial.

BACKGROUND: Although glucocorticoids are widely used in the treatment of patients with early rheumatoid arthritis, the best dosage of glucocorticoids with regards to efficacy and safety is not known.The aim of the study 'Comparison of the efficacy and safety of two starting dosages of prednisolone in early active rheumatoid arthritis' (CORRA) is to compare two standard glucocorticoid starting dosages and the non-use of glucocorticoids in the treatment of patients with early active rheumatoid arthritis on the background of the established 'anchor' therapy with methotrexate. METHODS/DESIGN: CORRA is an investigator-initiated, randomized, multicenter, double-blind, placebo-controlled trial with two treatment arms, starting with 60 mg or 10 mg prednisolone per day, tapered down to 5 mg prednisolone within eight weeks, and one placebo arm, each arm comprising 150 patients. The duration of the intervention is 12 weeks. In parallel, all patients will be treated with methotrexate (usual dosage 15 mg/week). The primary efficacy endpoint is the progression of radiographic joint damage after one year compared to baseline. Important secondary endpoints are the percentage of patients in remission, patient global assessment of disease activity, and changes of functional capacity. Safety monitoring is performed.The statistical analysis is performed in three hierarchical steps. The first step is an analysis of covariance (α = 0.05) to compare the group with the initial prednisolone dosage of 60 mg and the placebo group. In case of a statistically significant result, the comparison of the group starting with 10 mg prednisolone with the placebo group will be performed as a second step (α = 0.05). In case of superiority of the 10 mg prednisolone group versus the placebo group, the third step will be a non-inferiority test for the 10 mg prednisolone group versus the 60 mg prednisolone group (α = 0.025). DISCUSSION: The CORRA trial will yield information concerning the optimal glucocorticoid dosage schedule in the treatment of patients with early rheumatoid arthritis. TRIAL REGISTRATION: This trial was registered on 19 November 2013 at ClinicalTrials.gov. REGISTRATION NUMBER: NCT02000336.

Prevalence of anemia in elderly patients in primary care: impact on 5-year mortality risk and differences between men and women.

BACKGROUND: Increased mortality in patients with anemia has been demonstrated in disabled, seriously ill or hospitalized patients. In industrialized nations with their aging societies, however, elderly but apparently healthy family-physician patients are an important demographic group from a public-health perspective. We therefore set out to evaluate the prevalence of anemia in this group and associations between anemia and 5-year all-cause mortality, adjusted for multiple other established risk factors and chronic diseases. METHODS: This was a monitored, prospective cohort study in Germany with 344 representative family physicians who documented, consecutively, elderly patients (aged >or= 65 years). Extensive fasting plasma parameters were collected at baseline. Anemia at inclusion was defined according to World Health Organization criteria (hemoglobin below 12 g/dl in women and 13 g/dl in men). All participants were followed up for death of any cause for 5.3 years. RESULTS: Among the 6880 individuals, 2905 men and 3975 women, aged 65-95 (mean age 72.5), mild anemia (hemoglobin levels >or=10 g/dl) was found in 6.1% of women and 8.1% of men. Among those patients, 36.1% of anemic men and 15.0% of anemic women died. In a Cox proportional hazards analysis, multiple adjusted for potential confounders including major comorbidities, a near doubling of the 5-year mortality risk in anemic men (hazard ratio [HR] 1.9; 95% confidence interval [CI] 1.5-2.4) was found, while in anemic women there was no risk increase at all (HR 1.1; 95% CI 0.8-1.6). Even if patients with the lowest hemoglobin concentration (<11 g/dl for women, <12 g/dl for men) are singled out for multiple-adjusted analysis, anemia in men was related to a significant mortality risk (HR 3.3; 95% CI 2.1-5.1), but not in women (HR 1.85; 95% CI 0.97-3.53). CONCLUSION: In typical elderly patients without severe comorbidities, mild anemia was significantly associated with greater mortality in men but not in women. Given the impact of sex on outcomes of older subjects with mild anemia, the current definition of anemia should be adjusted for elderly males towards a higher hemoglobin threshold. Interventional trials will be needed to determine whether a consistent correction of anemia improves mortality of older men.