Reliability of a novel point of care device for monitoring diabetic peripheral neuropathy.

We aimed to assess DPNCheck's reliability for repeated sural nerve conduction (NC) parameters. This post hoc analysis used data from the randomized controlled ACUDPN trial assessing NC of the N. Suralis every eight weeks over a 6-month period in 62 patients receiving acupuncture against diabetic peripheral neuropathy (DPN) symptoms. The reliability of DPNCheck for nerve conduction velocity and amplitude was assessed using intraclass correlation coefficients (ICC) and was calculated using data from single time points and repeated measures design. The results of the NC measurements were correlated with the Total Neuropathy Score clinical (TNSc). Overall, for both nerve velocity and amplitude, the reliability at each measurement time point can be described as moderate to good and the reliability using repeated measures design can be described as moderate. Nerve velocity and amplitude showed weak correlation with TNSc. DPNCheck's reliability results question its suitability for monitoring DPN's progression. Given the limitation of our analysis, a long-term, pre-specified, fully crossed study should be carried out among patients with DPN to fully determine the suitability of the device for DPN progression monitoring. This was the first analysis assessing the reliability of the DPNCheck for DPN progression monitoring using data from multiple collection time points.

Homeopathy for seasonal allergic rhinitis: rationale, design and methods of the three-armed randomized controlled HOMEOSAR trial.

BACKGROUND: Patients with seasonal allergic rhinitis (SAR) frequently use homeopathic therapy. Although there is some evidence that homeopathy may be effective in treating symptoms of SAR, there is a lack of high-quality clinical trials. Therefore, the aim of the homeopathy for SAR (HOMEOSAR) trial is to determine the efficacy of individualized or standardized homeopathic drug treatment compared to placebo regarding rhinitis-related quality of life in patients with SAR. METHODS: This randomized, placebo-controlled, double-blind, three-armed intervention study will be conducted at two university hospital outpatient clinics for complementary and integrative medicine in Berlin and in 12 office-based practices specializing in homeopathic treatment in Germany. A total of 270 patients with clinical symptoms of SAR and positive allergy test to birch and grass pollen will receive homeopathic anamnesis and subsequently be randomized into (a) standardized homeopathic drug treatment with Galphimia Glauca (potency D6), (b) individualized homeopathic drug treatment (D6), or (c) placebo. All three groups can receive on-demand rescue medication as needed. Treatment will consist of two consultations and daily intake of the study medication for 4 weeks during the pollen season. The primary outcome is the mean overall score of the Rhinitis Quality of Life Questionnaire (RQLQ) in weeks 3 and 4, analyzed using analysis of covariance (adjusted for baseline RQLQ overall score and study center). A closed testing procedure will be used to control the overall type I error comparing the 3 treatment groups. Secondary outcomes include the overall RQLQ and its seven domain scores, responder status (decrease in RQLQ overall score of at least 0.5 points compared to the baseline value), use of rescue medication, intensity of total and individual SAR symptoms based on visual analog scale, generic health-related quality of life, safety, utilization of health care resources and associated costs. In addition, a qualitative data analysis is planned. CONCLUSION: The results of our study will contribute to clarifying the possible therapeutic effects of homeopathic drug treatment for patients with SAR. TRIAL REGISTRATION: This study has been registered in the German Clinical Trial Registry with trial ID DRKS00018081 on June 09, 2020.

Long-term health sequelae and quality of life at least 6 months after infection with SARS-CoV-2: design and rationale of the COVIDOM-study as part of the NAPKON population-based cohort platform (POP).

PURPOSE: Over the course of COVID-19 pandemic, evidence has accumulated that SARS-CoV-2 infections may affect multiple organs and have serious clinical sequelae, but on-site clinical examinations with non-hospitalized samples are rare. We, therefore, aimed to systematically assess the long-term health status of samples of hospitalized and non-hospitalized SARS-CoV-2 infected individuals from three regions in Germany. METHODS: The present paper describes the COVIDOM-study within the population-based cohort platform (POP) which has been established under the auspices of the NAPKON infrastructure (German National Pandemic Cohort Network) of the national Network University Medicine (NUM). Comprehensive health assessments among SARS-CoV-2 infected individuals are conducted at least 6 months after the acute infection at the study sites Kiel, Würzburg and Berlin. Potential participants were identified and contacted via the local public health authorities, irrespective of the severity of the initial infection. A harmonized examination protocol has been implemented, consisting of detailed assessments of medical history, physical examinations, and the collection of multiple biosamples (e.g., serum, plasma, saliva, urine) for future analyses. In addition, patient-reported perception of the impact of local pandemic-related measures and infection on quality-of-life are obtained. RESULTS: As of July 2021, in total 6813 individuals infected in 2020 have been invited into the COVIDOM-study. Of these, about 36% wished to participate and 1295 have already been examined at least once. CONCLUSION: NAPKON-POP COVIDOM-study complements other Long COVID studies assessing the long-term consequences of an infection with SARS-CoV-2 by providing detailed health data of population-based samples, including individuals with various degrees of disease severity. TRIAL REGISTRATION: Registered at the German registry for clinical studies (DRKS00023742).

Acupuncture in diabetic peripheral neuropathy-protocol for the randomized, multicenter ACUDPN trial.

BACKGROUND: Acupuncture is used to treat patients with diabetic peripheral neuropathy; however, the evidence is unclear. We present the design and methodology of the ACUDPN (ACUpuncture in Diabetic Peripheral Neuropathy) trial, which investigates the effectiveness of acupuncture for the treatment of diabetic peripheral neuropathy (DPN) symptoms. The aim of this study is to investigate whether acupuncture is effective for the treatment of DPN symptoms. METHODS: This study is a two-armed, randomized, controlled, parallel group, open-label, confirmatory, multicenter trial (8-week intervention period plus 16 weeks of follow-up). Physicians in outpatient units in Germany who specialize in acupuncture treatment will treat 110 diabetes type II patients with clinical symptoms of peripheral neuropathy in the feet and legs with signs of neuropathy according to nerve conduction testing. The patients will be randomized in a 1:1 ratio to one of the following two groups: (a) semi-standardized acupuncture plus routine care or (b) routine care alone. Acupuncture will consist of 12 treatments per patient over 8 weeks. The primary outcome will be the overall DPN-related complaints in the extremities after 8 weeks as measured by the Visual Analog Scale (VAS). Further outcome measures will include DPN-related pain, the Neuropathic Pain Symptom Inventory (NPSI), Diabetic Peripheral Neuropathic Pain Impact (DPNPI) scores, and nerve conduction parameters of the sural nerve at weeks 8, 16, and 24. DISCUSSION: The results of this trial will be available in 2021 and will help clarify whether acupuncture can be considered effective for the treatment of DPN with regard to the subdimensions of the neuropathic clinical picture. TRIAL REGISTRATION: ClinicalTrials.gov NCT03755960 . Registered on 11 August 2018.

Deep Vein Thrombosis in Europe-Health-Related Quality of Life and Mortality.

OBJECTIVES: Deep vein thrombosis (DVT) is a major health-care burden in Europe, but exact estimates are lacking. This study reports results from the PREFER venous thromboembolism (VTE) study concerning health-related quality of life (HrQoL) and mortality of patients with DVT. METHODS: PREFER VTE was a prospective, observational study, conducted in 7 European countries, designed to provide data concerning treatment patterns, resource utilization, mortality, and QoL. First-time or recurrent patients with DVT were followed at 1, 3, 6, and 12 months. Health-related QoL-as measured by the EuroQoL 5-Dimension 5-Level instrument ( EQ-5D-5L)-was analyzed using Tobit regression with repeated measures, assessing the impact of baseline characteristics stratified by cancer activity. Mortality was analyzed using logistic regression. RESULTS: At baseline, patients with DVT had a 0.14 lower EQ-5D-5L index score (0.72 for total sample) compared to the reference UK population (0.85). The EQ-5D-5L index score improved from baseline to 12 months in patients with active cancer (from 0.70 to 0.79) and those without (0.72-0.87); 7.3% died within a year, a 5.2% excess mortality compared to the age- and gender-adfjusted general population. The 12-month mortality rate of DVT varied between 2.9% in the pooled data from Germany, Switzerland, or Austria and 15.4% in Italy. Furthermore, the mortality rate differed between patients with active cancer and those without (42.9% vs 4.7%). CONCLUSIONS: Deep vein thrombosis is associated with a substantial burden of illness in terms of HrQoL at baseline, which following treatment normalizes after 12 months and has a significant mortality rate. In addition, active cancer has a significant impact on mortality and the HrQoL of patients with DVT.

Performance anxiety in professional musicians: a systematic review on prevalence, risk factors and clinical treatment effects.

Music performance anxiety (MPA) is one of the most common disorders among professional musicians, nevertheless, little is known about the disease. With this systematic review, prevalence, risk factors and treatment procedures for MPA were assessed, and for the first time, quality assessments were carried out for all studies using standardized assessment tools. A systematic literature search was conducted via search algorithms in the databases MEDLINE, EMBASE, CINAHL, PsycArticles, PsycInfo and ERIC. Included were case reports, case-control, cohort, cross-sectional and intervention studies examining professional musicians with MPA. For quality assessment, adapted tools of the National Heart, Lung, and Blood Institute were used. A total of 43 studies were included (10 case reports, 21 intervention, 11 cross-sectional, one cohort study). Quality ratings ranged from -11 to 6 out of a maximum of 15/16 points for cross-sectional/cohort studies and -4 to 11 out of 18 points for intervention studies. The prevalence of MPA was between 16.5% and 60%. More women than men were affected and musicians older than 45-50 years reported less MPA than younger musicians. Regarding treatment cognitive behavioural therapy (CBT) and ß-blockers were most often researched with beneficial results for CBT. However, studies with adequate control groups for CBT interventions are needed to clarify its efficacy. Studies showed methodological weaknesses, especially in the selection of participants, recording of influencing factors, blinding of interventions, randomization of participants and analysis of comorbidity. Recommendations for further research are made.

Deep-vein thrombosis in Europe - Burden of illness in relationship to healthcare resource utilization and return to work.

OBJECTIVES: Deep-vein thrombosis (DVT) forms a major healthcare burden in Europe, but exact estimates concerning the economic burden on society are lacking. This study reports results from the PREFER in VTE study concerning resource utilization and absence from work in DVT patients. METHODS: The PREFER in VTE registry was a prospective, observational, multicenter study carried out in Europe (France, Italy, Spain, the UK, and DACH [Germany, Switzerland and Austria]), designed to provide data concerning treatment patterns, resource utilization, mortality and quality of life. Patients with a first-time and/or recurrent DVT, were recruited and followed for 12 months. Data about resource utilization concerns resource utilization related to DVT. Specifically, treatment pattern, re-hospitalization rate, length of hospital stay, ambulatory/office visit, and proportion of patients returning to work, were analyzed and presented. Subgroup analysis by country and active cancer were also conducted. The length of hospital stay was analyzed as a function of demographics, previous events and co-morbidities using zero-inflated binomial negative regression. Similarly, time until return to work was analyzed using Cox regression. RESULTS: A total of 2056 patients with DVT were recruited, with an average age of 60 years. Patients with active cancer were mostly treated with heparin (83.9%), while patients without active cancer were treated with combinations of heparin, VKA and DOACs. DOACs were less often used in Spain and Italy (<7.0%). Following the management of their initial DVT 20.5% of the patients with and 12.2% of patients without active cancer (n = 88; n = 1462) were hospitalized for on average 8.2 and 10.1 days, respectively. The hospitalization-rate was highest in Italy (16.7%) and lowest in France (7.7%). Furthermore, the average length of stay was highest in Italy (16.6 days) and lowest in DACH (5.2 days). Physician visits were highest in DACH (9.3), lowest in the UK (2.6). Of those working, 50% returned to work at 1 month; >30% did not return to work within the year. CONCLUSIONS: Medical treatment of DVT differed between patients with active cancer and those without. Post-VTE or VTE-related resource utilization differs remarkably between countries. Work-loss seems high, but questions may be raised concerning the causality due to the presence of co-morbidities.

Patient characteristics in German allergological practices - a nationwide survey.

INTRODUCTION: In Western societies a significant incidence and prevalence of allergic asthma and other allergic diseases is observable. The present study investigated epidemiological patterns of allergic diseases and the utilization of health care resources by subjects who are already under specialized allergological treatment. Furthermore the study was performed to identify factors which had a significant impact on accessibility to specific immunotherapy (SIT). METHODS: The study was based on a cross-sectional survey on patient characteristics, which was performed by participating physicians, who were specialized in the field of allergological disorders and SIT, in collaboration with their patients. The analysis of data was divided into descriptive analyses and an analytical part, in which influencing factors for accessibility to specific immunotherapy were investigated. Logistic regression models to identify several predictor variables were used. RESULTS: 495 physicians documented the data of 19,990 patients. 18,177 patients were included in the analyses. Patients had a mean age of 31.5 ± 15.5 years and 53.2% were female. The most frequent and most severe allergic disorders observable in German allergological practices were conjunctivitis and rhinitis. The seasonal symptoms occurred mainly during March to August, while seasonal disease manifestation was 2.5 times more frequent than perennial forms. The most received anti-symptomatic medications are antihistamines and corticosteroids. Patients who receive SIT were mainly treated using subcutaneous immunotherapy (SCIT) - only in lower age groups, the likelihood of receiving sublingual immunotherapy (SLIT) was increased. CONCLUSION: In Germany, conjunctivitis and rhinitis are the most severe allergic disorders in allergological practices. Compared to the German general patient population, people who were already in allergological treatment had better access to SIT.

Subcutaneous specific immunotherapy: Economic implications from the perspective of statutory health insurance - a population based cost-effectiveness estimation.

BACKGROUND: Specific immunotherapy is the only potentially curative therapy in patients with allergic rhinitis (AR) and allergic asthma (AA). The present study examined the effects of subcutaneous immunotherapy (SCIT) on the financial situation of the German statutory health insurance systems and measures the impact on AR/AA prevalence during the next decades. A further objective was to identify possible SCIT-treatment strategies in order to reach an efficient SCIT-use. METHODS: Taking population projections of the German Statistical Federal Office, the number of expected new cases (AR, AA) was calculated until 2050. Based on assumptions about the proportion of patients who received SCIT in the future, age cohorts run through a model-calculation based on Markov chains. Data on effectiveness were extracted from published literature. For determining the cost situation of SCIT pharmacies we used selling prices for Allergovit®. All future costs are discounted at a mean rate of 2%. The model calculation was supplemented by a Delphi panel. RESULTS: Based on the current situation, a total annual economic burden of 540 million Euros is to be expected for care of about yearly 6 million patients with AR and AA in Germany between 2011 and 2050. Several scenarios have shown that the use of SCIT seems to be associated with cost savings from the perspective of statutory health insurances, when SCIT is offered to a larger amount of patients with moderate to severe symptoms. That would result in reduced number of expensive patients who suffer from AA. The best effects on the future number of diseased patients could be achieved, however, if SCIT additionally would be applied to patients in earlier stages of disease. Due to the large number of patients receiving SCIT in such a scenario, the initial costs would not completely compensated by cost savings. Nevertheless, the additional costs of 300 to 350 Euros per additionally healed patient seem to be justifiable. CONCLUSION: From the perspective of the SHI, SCIT is a useful strategic option for preventing the progression of allergic diseases. Particularly with increased use in early disease stages, the number of healed patients is high. Potential cost savings may result from increased treatment rates in patients with advanced disease stages.

[Atrial fibrillation in Germany: A prospective cost of illness study]. / Vorhofflimmern in Deutschland--eine prospektive Krankheitskostenstudie.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in clinical practice and associated with a high risk of stroke, heart failure and hospitalization. This study examines the indication-specific costs of illness of AF patients in Germany. METHODS: The study was conducted nationwide with 54 general practitioners and internists, as well as 12 practicing cardiologists. The observational period per patient was one year. Costs were calculated from the perspective of the German statutory health insurance. The study collected the annual direct indication-specific costs and additional patient relevant outcomes. RESULTS: Indication-specific services of 361 patients (age: 75, male: 55%) documented by general practitioners and internists cause average costs of 582 € per patient. The highest cost are caused by hospitalization (289 €), followed by outpatient treatment costs (151 €) and costs of anticoagulation with 52 € per patient. Additional consulting of a cardiologist (115 patients) causes average costs of 81 €. Assuming that a patient with AF is treated once a year by a resident cardiologist, the average annual cost amounted to 664 €. CONCLUSION: The results of this prospectively cost of illness analysis for AF patients under real life conditions in Germany indicate a high socio-economic burden of AF.

[Cost evaluation of a model for integrated care of seriously mentally ill patients]. / Kostenevaluation eines Modells der Integrierten Versorgung für schwer psychisch Kranke.

BACKGROUND: The model for integrated care (IC) of those seriously mentally ill patients insured with the DAK-Gesundheit health insurance and various Betriebskrankenkassen (members of the VAG Mitte) from the regions Berlin, Brandenburg, Lower Saxony and Bremen allows a complex treatment in the outpatient setting which consists of psychiatrists, general practitioners and clinicians, psychiatric nursing, sociotherapy (only in Berlin), internal medicine quality circles, orientation on treatment guidelines and conceptual consensus with the relevant care clinics. The aim of the evaluation is to illustrate the health economic effects of IC. METHODS: In the period from 2006 to 2010 insured members of the DAK-Gesundheit and other involved health insurance companies with a serious mental illness, a significant impairment of social functioning and the need to be treated to avoid or substitute an in-hospital stay were included in the integrated care. The cost perspective was that of the statutory health insurance companies. For the health economic evaluation, the utilisation of continuous IC over 18 months was compared to the last 18 months prior to the inclusion in IC. The clinical findings were gathered quarterly during the IC using CGI (Clinical Global Impressions) and GAF (Global Assessment of Functioning Scale). RESULTS: A total of 1 364 patients receiving IC in 66 doctor's practices were documented (of those, 286 had diagnoses of ICD-10 F2, 724 ICD-10 F32-F39). The median age was 48.8 years, 69% were female. 24% had their own source of income, 40% were on the pension, and the rest of the patients were receiving transfer benefits in some form. In 54% of the cases IC was used to avoid an in-hospital stay, in 46% of the cases to substitute an in-hospital stay. The degree of the CGI was 5.5 on average at the time of inclusion and the GAF score was 36.5 on average. The 226 patients with continuous documentation over 18 months were included in the health economic analysis. The number of days spent in hospital was lower during the IC period as compared to the 18 months prior to IV (11.8 vs. 28.6 days, p<0.001), the inpatient costs were lower (5 929 ± 13 837 Euro vs. 2 458 ± 6 940 Euro, p<0.001), the total was not significantly changed (7 777 ± 14 263 Euro vs. 7 321 ± 7 910 Euro, p=0.65). The substantial reduction of inpatient costs was compensated by the additional costs for medication and the costs of the complex outpatient care. Results were comparable for the 2 subgroups of schizophrenic/schizoaffective (n=66, 40.9 vs. 17.9 days, p=0.03; inpatient cost 9 009 ± 15 677 Euro vs. 3 650 ± 8 486 Euro, p=0.02; total expenditures 11 789 ± 15 975 Euro vs. 9 623 ± 9 262 Euro, p=0.33) and unipolar depressive patients (n=90, 29.8 vs. 9.8 days, p=0.006; inpatient cost 5 664 ± 14 921 Euro vs. 1 967 ± 5 276 Euro, p=0.02; total expenditures 7 146 ± 15 164 Euro vs. 6 234 ± 6 292 Euro, p=0.57). CONCLUSION: The IC was able to considerably reduce the utilisation of inpatient treatment through offering a complex range of services in the outpatient setting and allowed for a weight-shift in a low-threshold comprehensive care structure without an increase in costs from the statutory health insurance companies' perspective. For a detailed description of clinical effects further studies are required.

Mindful walking in psychologically distressed individuals: a randomized controlled trial.

Background. The aim of this randomized, controlled study was to investigate the effectiveness of a mindful walking program in patients with high levels of perceived psychological distress. Methods. Participants aged between 18 and 65 years with moderate to high levels of perceived psychological distress were randomized to 8 sessions of mindful walking in 4 weeks (each 40 minutes walking, 10 minutes mindful walking, 10 minutes discussion) or to no study intervention (waiting group). Primary outcome parameter was the difference to baseline on Cohen's Perceived Stress Scale (CPSS) after 4 weeks between intervention and control. Results. Seventy-four participants were randomized in the study; 36 (32 female, 52.3 ± 8.6 years) were allocated to the intervention and 38 (35 female, 49.5 ± 8.8 years) to the control group. Adjusted CPSS differences after 4 weeks were -8.8 [95% CI: -10.8; -6.8] (mean 24.2 [22.2; 26.2]) in the intervention group and -1.0 [-2.9; 0.9] (mean 32.0 [30.1; 33.9]) in the control group, resulting in a highly significant group difference (P < 0.001). Conclusion. Patients participating in a mindful walking program showed reduced psychological stress symptoms and improved quality of life compared to no study intervention. Further studies should include an active treatment group and a long-term follow-up.

Can I help you? Physicians' expectations as predictor for treatment outcome.

BACKGROUND: Patients' expectations of acupuncture treatment have widely been investigated; however, little focus has been on the physicians' expectations. We aimed to investigate (1) which patient characteristics lead to different expectations of physicians, and (2) whether physicians' expectations predict pain reduction and physical functioning in acupuncture and usual care treatment for chronic pain. METHODS: In four large multi-centre, randomized trials patients with chronic pain were randomized to receive usual care alone or 10 additional acupuncture treatments. Data were pooled. Baseline characteristics of the three expectation groups were compared, and the physicians' expectation and its interaction with the treatment group were included in two linear regression models predicting pain reduction and change in physical functioning. Other patient characteristics were included for adjustment. RESULTS: 9900 patients treated by 2781 physicians were analysed. Age, education and disease-related variables differed in the expectation groups. There was no interaction between treatment group and expectation. Patients, for whom the physicians had expected substantial improvement, showed more pain reduction (p < 0.001) and better physical functioning (p < 0.001) than patients for whom moderate improvement was expected. No significant differences were found between expected moderate and expected lack of success. However, the proportion of explained variance that was due to physicians' expectations was small considering total explained variance. CONCLUSIONS: Physicians' high expectations at baseline predict better outcome, independent of the treatment. Since we adjusted for several patient variables including duration and severity of disease, this cannot be explained by prognostic factors only. Other explanations are discussed and recommended for future research.

[Cardiovascular diseases in the focus of health economics. The example of drug-eluting vascular stents in coronary heart disease]. / Herz-Kreislauf-Erkrankungen im Fokus der Gesundheitsökonomie. Das Beispiel medikamentenfreisetzender Gefäßstents bei koronarer Herzerkrankung.

Coronary heart disease is an important disorder in Western industrialized societies, with regard to both the epidemiologic and economic burden of illness. A modern therapeutic strategy consists of coronary interventions and the implantation of drug-eluting vascular stents. The cost-effectiveness of such drug-eluting stents has been an important subject of health-economic evaluation research in recent years. This article presents two examples of such studies and deals with the question whether existing study projects are able to provide sufficient evidence for allocation decisions in health care. On this basis we discuss important challenges for future health economic analysis. A key conclusion is the need for long-term and cross-sectoral evaluation strategies that could be based on routinely collected health care data. Supplemented by health economic results from clinical trials, the use of such data would lead to a broader data basis for allocation decisions in health care.

[Clinical and health economic challenges of personalized medicine]. / Herausforderungen an die klinische Evaluation und Gesundheitsökonomie auf dem Weg zur personalisierten Medizin.

Healthcare systems across the globe are currently challenged by aging populations, increases in chronic diseases and the difficult task of managing a healthcare budget. In this health economic climate, personalized medicine promises not only an improvement in healthcare delivery but also the possibility of more cost-effective therapies. It is important to remember, however, that personalized medicine has the potential to both increase and decrease costs. Each targeted therapy must be evaluated individually. However, standard clinical trial design is not suitable for personalized therapies. Therefore, both scientists and regulatory authorities will need to accept innovative study designs in order to validate personalized therapies. Hence correct economic evaluations are difficult to carry out due to lack of clear clinical evidence, longitudinal accounting and experience with patient/clinician behavior in the context of personalized medicine. In terms of reimbursement, payers, pharmaceutical companies and companion diagnostic manufacturers will also need to explore creative risk-sharing concepts. Germany is no exception to the challenges that face personalized medicine and for personalized medicine to really become the future of medicine many health economic challenges first need to be overcome. The health economic implications of personalized medicine remain unclear but it is certain that the expansion of targeted therapies in current healthcare systems will create a host of challenges.