IgE to cross-reactive carbohydrate determinants (CCD) in childhood: Prevalence, risk factors, putative origins.

BACKGROUND: IgE antibodies to cross-reactive carbohydrate determinants (CCD) are usually clinically irrelevant but they can be a cause of false positive outcomes of allergen-specific IgE tests in vitro. Their prevalence and levels have been so far cross-sectionally examined among adult allergic patients and much less is known about their origins and relevance in childhood. METHODS: We examined CCD with a cross-sectional approach in 1263 Italian pollen allergic children (Panallergen in Paediatrics, PAN-PED), as well as with a longitudinal approach in 612 German children (Multicenter Allergy Study, MAS), whose cutaneous and IgE sensitization profile to a broad panel of allergen extracts and molecules was already known. The presence and levels of IgE to CCD were examined in the sera of both cohorts using bromelain (MUXF3) as reagent and a novel chemiluminescence detection system, operating in a solid phase of fluorescently labelled and streptavidin-coated paramagnetic microparticles (NOVEOS, HYCOR, USA). RESULTS: IgE to CCD was found in 22% of the Italian pollen allergic children, mainly in association with an IgE response to grass pollen. Children with IgE to CCD had higher total IgE levels and were sensitized to more allergenic molecules of Phleum pratense than those with no IgE to CCD. Among participants of the German MAS birth cohort study, IgE to CCD emerged early in life (even at pre-school age), with IgE sensitization to group 1 and 4 allergen molecules of grasses, and almost invariably persisted over the full observation period. CONCLUSIONS: Our results contribute to dissect the immunological origins, onset, evolution and risk factors of CCD-sIgE response in childhood, and raise the hypothesis that group 1 and/or 4 allergen molecules of grass pollen are major inducers of these antibodies through an antigen-specific, T-B cell cognate interaction.

Self-care strategies for medical students: an uncontrolled mixed-methods evaluation of a mind-body-medicine group course.

BACKGROUND: High stress during medical education and its detrimental effects on student health is well documented. This exploratory evaluation study assesses a 10-week Mind-Body-Medicine student course, created to promote student self-care at Charité Universitätsmedizin Berlin, Germany. METHODS: During 2012-2019, uncontrolled quantitative and qualitative data were gathered from 112 student participants. Outcomes including changes in perceived stress (PSS), mindfulness (FMI/MAAS), self-reflection (GRAS), self-efficacy (GSE), empathy (SPF), and health-related quality of life (SF-12) were measured between the first (T0) and last sessions (T1). Qualitative data were obtained in focus groups at course completion and triangulated with quantitative data. RESULTS: Quantitative outcomes showed decreases in perceived stress and increased self-efficacy, mindfulness, self-reflection, and empathy. In focus groups, students reported greater abilities to self-regulate stressful experiences, personal growth and new insights into integrative medicine. Triangulation grounded these effects of MBM practice in its social context, creating an interdependent dynamic between experiences of self and others. CONCLUSION: After completing an MBM course, students reported reduced perceived stress, increased self-efficacy, mindfulness, empathy and positive engagement with integrative concepts of doctor-patient relationships. Further research with larger randomized confirmatory studies is needed to validate these benefits.

Development, Implementation, and Evaluation of an e-Learning in Integrative Oncology for Physicians and Students Involving Experts and Learners: Experiences and Recommendations.

In this project, an e-Learning program for complementary and integrative medicine in oncology was systematically developed, implemented, and evaluated in a stepwise procedure. Learning objectives and content were defined within the KOKON project network, considering the educational competencies for integrative oncology. To design a valuable e-Learning, experts were involved in all relevant steps of the process, as well as stakeholders from various target groups (undergraduates: medicine students, postgraduates: oncology physicians). We used mixed methods including quantitative surveys, progress tests, and qualitative focus groups. The developed e-Learning program led to a significant measurable knowledge gain about complementary and integrative medicine. In parallel, physicians and students were subjectively satisfied with the training. For the majority of e-Learning elements, the needs of both target groups are comparable. Furthermore, both groups emphasized the value of formative assessment tools for gaining knowledge. From the various surveys and experiences collected in this project, we derive recommendations for others developing e-Learning programs.

A singleplex IgE test to a mixture of molecules from multiple airborne allergen sources: Innovating in vitro screening of respiratory allergies.

BACKGROUND: In vitro immunoglobulin E (IgE) tests can be better standardized if based on molecules rather than extracts. However, singleplex screening tests for respiratory or food allergies are still based on extracts only. TARGET: To validate a novel singleplex IgE screening test for respiratory allergies, based on a mix of major allergenic molecules Der p 1, Der p 2, Fel d 1, Can f 1, Can f 2, Can f 3, Can f 5, Bet v 1, Phl p 1, and Art v 1 (Molecular SX01, NOVEOS, HYCOR, USA), and requiring only four microliters (µl) of serum. METHODS: We examined six subsets of sera from participants of the German Multicenter Allergy Study (MAS) birth cohort enrolling 1314 newborns during 1990: (1) monosensitized (n = 58); (2) polysensitized (n = 24); (3) nonsensitized, with total IgE levels above (n = 24) or (4) below (n = 24) 300 kU/L; (5) sensitized to milk and/or egg but not to airborne allergens (n = 24); and (6) sera of children aged ≤5 years at their earliest IgE monosensitization to airborne allergens (n = 41). Sera were analyzed with the novel molecular SX01 test (NOVEOS) and with three categories of comparators: ImmunoCAP Phadiatop SX01, extracts, and molecules of D. pteronyssinus, cat, dog, grass, and birch. Sensitivity, specificity, positive and negative predictive values were calculated. Quantitative interrelationships were determined using Spearman's rank-order correlation coefficient and Bland-Altmann plots. RESULTS: The molecular SX01 test predicted the outcome of IgE tests based on molecules, extracts, or Phadiatop in 188 (96.4%), 171 (87.7%), and 171 (87.7%) of the 195 sera, respectively. Accordingly, sensitivity was 93.5%, 89.0%, and 82.4%, whereas specificity was 100%, 97.6%, and 96.1% when compared with molecular, extract, and Phadiatop tests, respectively. Inconsistent outcomes were largely confined to sera with IgE-Ab levels around the cutoff value of 0.35 kU/L, except for 5/195 (2.5%) sera, containing high levels of IgE to Phl p 5 and/or Alt a 1 only. IgE levels measured by the molecular SX01 test and with IgE tests to molecules, extracts, and Phadiatop were highly correlated (rho 0.90; p < .001), (rho 0.87, p < .001), (rho 0.84, p < .001), respectively. The novel molecular SX01 test detected IgE-Ab in 27/28 (sensitivity 96.4%) of the sera of preschool children at their earliest IgE sensitization to the same molecules. DISCUSSION: Our study validates the prototype of a novel category of IgE test, based on molecular mixes. The test's rather good precision and accuracy in early screening IgE sensitization to airborne allergens in German children may be further improved by adding a few other molecules, such as Phl p 5 and Alt a 1.

SARS-CoV-2 infections in professional orchestra and choir musicians-a prospective cohort study.

During the COVID-19 pandemic, rehearsal and concert activities of professional orchestras and choirs were severely restricted based on the assumption of particularly high infection risks associated with wind instruments and singing. Therefore, our primary objective was to determine the incidence of SARS-CoV-2 infections in orchestra and choir musicians compared to controls. We also assessed influenza, flu, upper respiratory tract infections, and course of illness. Musicians from professional orchestras and choirs and controls from 23 institutions throughout Germany were included in a prospective cohort study. Data were collected from October 2020 to June 2021 by weekly online surveys. A mixed-effects cox proportional hazards model was used to assess the effect of exposure by professional activity on SARS-CoV-2 infection. In 1,097 participants (46.7 years (SD 10.3); 46.8% female; 705 orchestra, 154 choir, and 238 control subjects) 40 SARS-CoV-2 infections occurred. Cases per person-years were 0.06 in orchestras, 0.11 in choirs, and 0.03 in controls. Hazard ratios compared to controls were 1.74 (95% CI 0.58 to 5.25, p = 0.320) for orchestra musicians and 2.97 (0.87 to 10.28, p = 0.087) for choir singers. Infection source was suspected predominantly in private contexts. Disease courses were mild to moderate. Other respiratory infections were reported in 6.1% of study weeks in orchestras, 10.1% in choirs, and 8.0% in controls. Sick leave days of total study days were 0.5, 2.1 and 1.3%, respectively. This epidemiologic study during the pandemic in professional musicians indicates no increased risk of SARS-CoV-2 infections in orchestra musicians and a trend towards increased risk in choir singers compared to controls. However, the exact routes of infection could not be validated. If appropriate hygiene concepts are adhered to, safe orchestra and choir activity appears possible in pandemic times.

Der p 23-specific IgE response throughout childhood and its association with allergic disease: A birth cohort study.

BACKGROUND: The Dermatophagoides pteronyssinus molecule Der p 23 is a major allergen whose clinical relevance has been shown in cross-sectional studies. We longitudinally analysed the trajectory of Der p 23-specific IgE antibody (sIgE) levels throughout childhood and youth, their early-life determinants and their clinical relevance for allergic rhinitis and asthma. METHODS: We obtained sera and clinical data of 191 participants of the German Multicentre Allergy Study, a prospective birth cohort. Serum samples from birth to 20 years of age with sIgE reactivity to Der p 23 in a customised semiquantitative microarray were newly analysed with a singleplex quantitative assay. Early mite exposure was assessed by measuring the average content of Der p 1 in house dust at 6 and 18 months. RESULTS: Der p 23-sIgE levels were detected at least once in 97/191 participants (51%). Prevalence of Der p 23 sensitisation and mean sIgE levels increased until age 10 years, plateaued until age 13 years and were lowest at age 20 years. Asthma, allergic rhinitis (AR) and atopic dermatitis (AD) were more prevalent in Der p 23-sensitised children, including those with monomolecular but persistent sensitisation (11/97, 11%). A higher exposure to mites in infancy and occurrence of AD before 5 years of age preceded the onset of Der p 23 sensitisation, which in turn preceded a higher incidence of asthma. CONCLUSIONS: Der p 23 sensitisation peaks in late childhood and then decreases. It is preceded by early mite exposure and AD. Asthma and AR can occur in patients persistently sensitised to Der p 23 as the only mite allergen, suggesting the inclusion of molecular testing of Der p 23-sIgE for subjects with clinical suspicion of HDM allergy but without sIgE to other major D.pt. allergens.

Acupuncture and osteopathic medicine for atopic dermatitis: a three-armed, randomized controlled explorative clinical trial.

BACKGROUND: Patients with atopic dermatitis (AD) frequently use acupuncture (ACU) and osteopathic medicine (OM), although their therapeutic benefits are unclear. AIM: To investigate the effectiveness of ACU and OM in patients with AD. METHODS: In a three-armed, single-centre, randomized controlled open explorative clinical trial, adult patients with AD received ACU, OM or no study intervention (control group; CG) plus routine care. Outcomes included disease severity (SCORing Atopic Dermatitis; SCORAD), itching intensity (visual analogue scale; VAS), frequency of topical corticosteroid (TCS) use over 7 days and cost-effectiveness. Endpoints were analysed by analysis of covariance adjusted for the respective baseline value and TCS use. RESULTS: Overall, 121 patients (92 women, 29 men) with a mean ± SD age of 31.4 ± 10.5 years were randomized. After 12 weeks, the adjusted means (95% CI) for ACU, OM and control were, respectively, 22.3 (18.3-26.3), 26.4 (22.6-30.2) and 23.7 (19.9-27.5) for SCORAD (P = 0.32); 27.9 (19.5-36.4), 35.0 (26.9-43.0) and 42.3 (34.7-50.0) for VAS itching (P < 0.05); and 2.3 (0.8-3.9), 1.9 (0.4-3.5) and 4.3 (2.6-6.0), for TCS use (P = 0.10). ACU and OM were not cost-effective compared with the CG. CONCLUSION: Although no differences in disease severity were found, our findings indicate that ACU might reduce itching in patients with AD. Furthermore, ACU and OM showed a trend towards reducing TCS use.

Ayurveda in Knee Osteoarthritis-Secondary Analyses of a Randomized Controlled Trial.

Background: Ayurveda is widely practiced in South Asia in the treatment of osteoarthritis (OA). The aim of these secondary data analyses were to identify the most relevant variables for treatment response and group differences between Ayurvedic therapy compared to conventional therapy in knee OA patients. Methods: A total of 151 patients (Ayurveda n = 77, conventional care n = 74) were analyzed according to the intention-to-treat principle in a randomized controlled trial. Different statistical approaches including generalized linear models, a radial basis function (RBF) network, exhausted CHAID, classification and regression trees (CART), and C5.0 with adaptive boosting were applied. Results: The RBF network implicated that the therapy arm and the baseline values of the WOMAC Index subscales might be the most important variables for the significant between-group differences of the WOMAC Index from baseline to 12 weeks in favor of Ayurveda. The intake of nutritional supplements in the Ayurveda group did not seem to be a significant factor in changes in the WOMAC Index. Ayurveda patients with functional limitations > 60 points and pain > 25 points at baseline showed the greatest improvements in the WOMAC Index from baseline to 12 weeks (mean value 107.8 ± 27.4). A C5.0 model with nine predictors had a predictive accuracy of 89.4% for a change in the WOMAC Index after 12 weeks > 10. With adaptive boosting, the accuracy rose to 98%. Conclusions: These secondary analyses suggested that therapeutic effects cannot be explained by the therapies themselves alone, although they were the most important factors in the applied models.

App-Based Relaxation Exercises for Patients With Chronic Neck Pain: Pragmatic Randomized Trial.

BACKGROUND: Chronic neck pain is a highly prevalent condition. Learning a relaxation technique is recommended by numerous guidelines for chronic neck pain. Smartphone apps can provide relaxation exercises; however, their effectiveness, especially in a self-care setting, is unclear. OBJECTIVE: The aim of this pragmatic randomized trial is to evaluate whether app-based relaxation exercises, including audio-based autogenic training, mindfulness meditation, or guided imagery, are more effective in reducing chronic neck pain than usual care alone. METHODS: Smartphone owners aged 18 to 65 years with chronic (>12 weeks) neck pain and the previous week's average neck pain intensity ≥4 on the Numeric Rating Scale (0=no pain to 10=worst possible pain) were randomized into either an intervention group to practice app-based relaxation exercises or a control group (usual care and app for data entry only). For both groups, the follow-up data were collected using app-based diaries and questionnaires. The primary outcome was the mean neck pain intensity during the first 3 months based on daily measurements. Secondary outcomes included neck pain based on weekly measurements, pain acceptance, neck pain-related stress, sick-leave days, pain medication intake, and adherence, which were all measured until the 6-month follow-up. For the primary analysis, analysis of covariance adjusted for baseline neck pain intensity was used. RESULTS: We screened 748 participants and enrolled 220 participants (mean age 38.9, SD 11.3 years; mean baseline neck pain 5.7, SD 1.3 points). The mean neck pain intensity in both groups decreased over 3 months; however, no statistically significant difference between the groups was found (intervention: 4.1 points, 95% CI 3.8-4.4; control: 3.8 points, 95% CI 3.5-4.1; group difference: 0.3 points, 95% CI -0.2 to 0.7; P=.23). In addition, no statistically significant between-group differences regarding neck pain intensity after 6 months, responder rate, pain acceptance, pain medication intake, or sick-leave days were observed. There were no serious adverse events that were considered related to the trial intervention. In week 12, only 40% (44/110) of the participants in the intervention group continued to practice the exercises with the app. CONCLUSIONS: The study app did not effectively reduce chronic neck pain or keep the participants engaged in exercising in a self-care setting. Future studies on app-based relaxation interventions should take into account the most recent scientific findings for behavior change techniques. TRIAL REGISTRATION: ClinicalTrials.gov NCT02019134; https://clinicaltrials.gov/ct2/show/NCT02019134. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/1745-6215-15-490.

Strategies to Enhance Retention in a Cohort Study Among Adults of Turkish Descent Living in Berlin.

Retention is important for statistical power and external validity in long-term cohort studies. The aims of our study were to evaluate different retention strategies within a cohort study of adults of Turkish descent in Berlin, Germany, and to compare participants and non-participants. In 2011-2012, a population-based study was conducted among adults of Turkish descent to primarily examine recruitment strategies. 6 years later, the participants were re-contacted and invited to complete a self-report questionnaire regarding their health status, health care utilization, and satisfaction with medical services. The retention strategy comprised letters in both German and Turkish, phone calls, and home visits (by bilingual staff). We calculated the response rate and retention rate, using definitions of the American Association for Public Opinion Research, as well as the relative retention rate for each level of contact. Associations of baseline recruitment strategy, sociodemographic, migration-related and health-related factors with retention were investigated by logistic regression analysis. Of 557 persons contacted, 249 (44.7%) completed the questionnaire. This was 50.1% of those whose contact information was available. The relative retention rate was lowest for phone calls (8.9%) and highest for home visits (18.4%). Participants were more often non-smokers and German citizens than non-participants. For all remaining factors, no association with retention was found. In this study, among adults of Turkish descent, the retention rate increased considerably with every additional level of contact. Implementation of comprehensive retention strategies provided by culturally matched study personnel may lead to higher validity and statistical power in studies on migrant health issues.

Predictors of Changes in Physical Activity and Sedentary Behavior during the COVID-19 Pandemic in a Turkish Migrant Cohort in Germany.

The new coronavirus (COVID-19) pandemic and the resulting response measures have led to severe limitations of people's exercise possibilities with diminished physical activity (PA) and increased sedentary behavior (SB). Since for migrant groups in Germany, no data is available, this study aimed to investigate factors associated with changes in PA and SB in a sample of Turkish descent. Participants of a prospective cohort study (adults of Turkish descent, living in Berlin, Germany) completed a questionnaire regarding COVID-19 related topics including PA and SB since February 2020. Changes in PA and SB were described, and sociodemographic, migrant-related, and health-related predictors of PA decrease and SB increase were determined using multivariable regression analyses. Of 106 participants, 69% reported a decline of PA, 36% reported an increase in SB. PA decrease and SB increase seemed to be associated with inactivity before the pandemic as well as with the female sex. SB increase appeared to be additionally associated with educational level and BMI. The COVID-19 pandemic and the response measures had persistent detrimental effects on this migrant population. Since sufficient PA before the pandemic had the strongest association with maintaining PA and SB during the crisis, the German government and public health professionals should prioritize PA promotion in this vulnerable group.

Current practice of stakeholder engagement: researchers' experiences in North America, DACH countries and China.

Aim: To explore the current practice of stakeholder engagement in clinical trials and its evaluation in North America (USA and Canada), DACH countries (Germany, Austria and Switzerland) and China. Participants & methods: We conducted a web-based, anonymous, international, cross-sectional online survey for clinical researchers. Data were analyzed using descriptive and explorative statistical analysis including analysis of variance and analysis of covariance. Results: Stakeholder engagement is more prominent and higher accepted among researchers in North America. Researchers in DACH countries have less knowledge of the stakeholder engagement method and are less likely to apply it. Conclusion: Stakeholder engagement is perceived very differently among participants from DACH countries, North America and China. For a broader acceptance and implementation institutional support and motivational conditions might be needed.

Association of Acculturation Status with Longitudinal Changes in Health-Related Quality of Life-Results from a Cohort Study of Adults with Turkish Origin in Germany.

Health-related quality of life (HRQL) among migrant populations can be associated with acculturation (i.e., the process of adopting, acquiring and adjusting to a new cultural environment). Since there is a lack of longitudinal studies, we aimed to describe HRQL changes among adults of Turkish descent living in Berlin and Essen, Germany, and their association with acculturation. Participants of a population-based study were recruited in 2012-2013 and reinvited six years later to complete a questionnaire. Acculturation was assessed at baseline using the Frankfurt acculturation scale (integration, assimilation, separation and marginalization). HRQL was assessed at baseline (SF-8) and at follow-up (SF-12) resulting in a physical (PCS) and mental (MCS) sum score. Associations with acculturation and HRQL were analyzed with linear regression models using a time-by-acculturation status interaction term. In the study 330 persons were included (65% women, mean age ± standard deviation 43.3 ± 11.8 years). Over the 6 years, MCS decreased, while PCS remained stable. While cross-sectional analyses showed associations of acculturation status with both MCS and PCS, temporal changes including the time interaction term did not reveal associations of baseline acculturation status with HRQL. When investigating HRQL in acculturation, more longitudinal studies are needed to take changes in both HRQL and acculturation status into account.

Effects of training oncology physicians advising patients on complementary and integrative therapies on patient-reported outcomes: A multicenter, cluster-randomized trial.

BACKGROUND: Many patients with cancer do not disclose complementary medicine use but want their physician's advice on this matter. This study evaluated whether using blended learning (e-learning plus a workshop) to train oncology physicians in providing advice on complementary and integrative medicine (CIM) therapies to their patients with cancer, in addition to distributing an information leaflet on reputable CIM websites, had different effects on patient-reported outcomes for the consultation than only distributing the leaflet. METHODS: In this multicenter, cluster-randomized trial, patients from private practices/hospital departments, recruited by 48 oncology physicians randomly allocated to an intervention group (CIM consultation plus information leaflet) or a control group (information leaflet), received CIM information. Patient-reported outcomes included satisfaction (Patient Satisfaction With Information on Cancer Treatment), readiness to make a decision (Preparation for Decision Making), and physician-patient communication (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire and Communication 26 [EORTC QLQ-COMU26]) for the consultation. Qualitative interviews were conducted with a physician subsample. RESULTS: A total of 291 patients (128 in the intervention group and 169 in the control group) advised by 41 physicians participated. Patients in the intervention group rated physician-patient communication higher on all EORTC QLQ-COMU26 scales (mean total score, 84.3 [95% CI, 79.5-89.2] vs 73.6 [95% CI, 69.3-78.0]; P = .002), were more satisfied with the advice (mean, 4.2 [95% CI, 4.0-4.4] vs 3.7 [95% CI, 3.5-3.8]; P < .001), and were readier to make a decision (mean, 63.5 [95% CI, 57.4-69.6] vs 53.2 [95% CI, 47.8-58.7]; P = .016) than the control group. Physicians who reported patients in both settings seemed satisfied with the advice given. CONCLUSIONS: This study evaluated a novel education intervention for training oncology physicians in providing CIM advice in routine care. Providing structured CIM consultations had positive effects on patient satisfaction, readiness to make decisions, and physician-patient communication.

Correction to: Effectiveness and cost-effectiveness of treatment with additional enrollment to a homeopathic integrated care contract in Germany.

An amendment to this paper has been published and can be accessed via the original article.

Physical Activity Trajectories among Persons of Turkish Descent Living in Germany-A Cohort Study.

Physical activity (PA) behavior is increasingly described as trajectories taking changes over a longer period into account. Little is known, however, about predictors of those trajectories among migrant populations. Therefore, the aim of the present cohort study was to describe changes of PA over six years and to explore migration-related and other predictors for different PA trajectories in adults of Turkish descent living in Berlin. At baseline (2011/2012) and after six years, sociodemographics, health behavior, and medical information were assessed. Four PA trajectories were defined using data of weekly PA from baseline and follow-up: "inactive", "decreasing", "increasing", and "stable active". Multivariable regression analyses were performed in order to determine predictors for the "stable active" trajectory, and results were presented as adjusted odds ratios (aOR) with 95% confidence intervals (95%CI). In this analysis, 197 people (60.9% women, mean age ± standard deviation 49.9 ± 12.8 years) were included. A total of 77.7% were first-generation migrants, and 50.5% had Turkish citizenship. The four PA trajectories differed regarding citizenship, preferred questionnaire language, and marital status. "Stable active" trajectory membership was predicted by educational level (high vs. low: aOR 4.20, 95%CI [1.10; 16.00]), citizenship (German or dual vs. Turkish only: 3.60 [1.20; 10.86]), preferred questionnaire language (German vs. Turkish: 3.35 [1.05; 10.66]), and BMI (overweight vs. normal weight: 0.28 [0.08; 0.99]). In our study, migration-related factors only partially predicted trajectory membership, however, persons with citizenship of their country of origin and/or with poor language skills should be particularly considered when planning PA prevention programs.

Effectiveness and cost-effectiveness of treatment with additional enrollment to a homeopathic integrated care contract in Germany.

BACKGROUND: A number of German statutory health insurance companies are offering integrated care contracts for homeopathy (ICCHs) that cover the reimbursement of homeopathic treatment. The effectiveness and cost-effectiveness of these contracts are highly debated. METHODS: To evaluate the effectiveness and cost-effectiveness of treatment after an additional enrollment in an ICCH, a comparative, prospective, observational study was conducted in which participants in the ICCH (HOM group) were compared with matched (on diagnosis, sex and age) insured individuals (CON group) who received usual care alone. Those insured with either migraine or headache, allergic rhinitis, asthma, atopic dermatitis and depression were included. Primary effectiveness outcomes were the baseline adjusted scores of diagnosis-specific questionnaires (e.g. RQLQ, AQLQ, DLQI, BDI-II) after 6 months. Primary cost-effectiveness endpoints were the baseline adjusted total costs from an insurer perspective in relation to the achieved quality-adjusted life years (QALYs). Costs were derived from health claims data and QALYs were calculated based on SF-12 data. RESULTS: Data from 2524 participants (1543 HOM group) were analyzed. The primary effectiveness outcomes after six months were statistically significant in favor of the HOM group for migraine or headache (Δ = difference between groups, days with headache: - 0.9, p = 0.042), asthma (Δ-AQLQ(S): + 0.4, p = 0.014), atopic dermatitis (Δ-DLQI: - 5.6, p ≤ 0.001) and depression (Δ-BDI-II: - 5.6, p ≤ 0.001). BDI-II differences reached the minimal clinically important difference. For all diagnoses, the adjusted mean total costs over 12 months were higher in the HOM group from an insurer perspective, with migraine or headache, atopic dermatitis and depression suggesting cost-effectiveness in terms of additional costs per QALY gained. CONCLUSION: After an additional enrollment in the ICCH, the treatment of participants with depression showed minimally clinically relevant improvements. From an insurer perspective, treatment with an ICCH enrollment resulted in higher costs over all diagnoses but seemed to be cost-effective for migraine or headache, atopic dermatitis and depression according to international used threshold values. Based on the study design and further limitations, our findings should be considered cautiously and no conclusions regarding the effectiveness of specific treatment components can be made. Further research is needed to overcome limitations of this study and to confirm our findings. TRIAL REGISTRATION: clinicaltrials.gov , NCT01854580. Registered 15 March 2013 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01854580.

Orally applied bacterial lysate in infants at risk for atopy does not prevent atopic dermatitis, allergic rhinitis, asthma or allergic sensitization at school age: Follow-up of a randomized trial.

BACKGROUND: The allergy preventive effects of gut immune modulation by bacterial compounds are still not fully understood. OBJECTIVE: We sought to evaluate the effect of bacterial lysate applied orally from the second until seventh months of life on the prevalence of allergic diseases at school age. METHODS: In a randomized, placebo-controlled trial, 606 newborns with at least one allergic parent received orally a bacterial lysate consisting of heat-killed Gram-negative Escherichia coli Symbio and Gram-positive Enterococcus faecalis Symbio or placebo from week 5 until the end of month 7. A total of 402 children were followed until school age (6-11 years) for the assessment of current atopic dermatitis (AD), allergic rhinitis (AR), asthma and sensitization against aeroallergens. RESULTS: AD was diagnosed in 11.0% (22/200) of children in the active and in 10.4% (21/202) of children in the placebo group. AR was diagnosed in 35% (70/200) of children in the active and in 38.1% (77/202) children in the placebo group. Asthma was diagnosed in 9% (18/199) of children in the active and in 6.6% (13/197) of children in the placebo group. Sensitization occurred in 46.5% (66/142) of participants in the active and 51.7% (76/147) in the placebo group. CONCLUSION: An oral bacterial lysate of heat-killed Gram-negative Escherichia coli and Gram-positive Enterococcus faecalis applied during the first 7 months of life did not influence the development of AD, asthma and AR at school age.

Reliability of Ayurvedic Diagnosis for Knee Osteoarthritis Patients: A Nested Diagnostic Study Within a Randomized Controlled Trial.

Background: Ayurveda is a traditional Indian system of medicine. The customized Ayurvedic approach consists of a combination of several diagnostic procedures and subsequent individualized therapeutic interventions. Evaluation of inter-rater reliability (IRR) of Ayurvedic diagnoses has rarely been performed. The aim of this study was to evaluate IRR of Ayurvedic diagnosis for patients with knee osteoarthritis. Methods: A diagnostic reliability study of 30 patients and 4 Ayurvedic experts was nested in a randomized controlled trial. Patients were diagnosed in a sequential order by all experts utilizing a semistructured patient history form. A nominal group technique as consensus procedure was performed to reach agreement on the items to be diagnosed. An IRR analysis using Fleiss' and Cohen's kappa statistics was performed to determine a chance-corrected measure of agreement among raters. Results: One hundred and twenty different ratings and 30 consensus ratings were performed and analyzed. While high percentages of agreement for main diagnostic entities and the final Ayurveda diagnosis (95% consensus agreement on main diagnosis) could be observed, this was not reflected in the corresponding kappa values, which largely yielded fair-to-poor inter-rater agreement kappas for central diagnostic aspects such as prakriti and agni (κ values between 0 and 0.4). Notably, agreement on disease-related entities was better than that on constitutional entities. Conclusions: This is the first diagnostic study embedded in a clinical trial on patients with knee osteoarthritis utilizing a multimodality whole systems approach. Results showed a contrast between the high agreement of the consented final diagnosis and disagreement on certain diagnostic details. Future diagnostic studies should have larger sample sizes and a methodology more tailored to the specificities of traditional whole systems of medicine. Equal emphasis will need to be placed on all core diagnostic components of Ayurveda, both constitutional and disease specific, using detailed structured history taking forms.

The Value of Treatment Processes in Germany: A Discrete Choice Experiment on Patient Preferences in Complementary and Conventional Medicine.

BACKGROUND: The effects of health interventions are often complex, and it is argued that they comprise more than pure changes in clinical parameters. Aspects of the treatment process, so-called 'benefits beyond health', are often overlooked in the evaluation of health interventions but can be of value to the patients. OBJECTIVES: The aim of this study was to assess patients' preferences and willingness to pay regarding the treatment process and its attributes in patients using acupuncture, homeopathy or general medicine (GM). METHODS: A systematic literature search, six semi-structured interviews and a stakeholder involvement were conducted to determine the attributes of the treatment process. Five process attributes and one cost attribute were used to construct the experimental design of the discrete choice experiment (DCE) (6 × 3), a cross sectional survey method. Patients were recruited by outpatient physicians practicing in Berlin and Munich, Germany. Process attributes were effects-coded. Data were analyzed in a conditional logit regression. RESULTS: Data from 263 patients were analyzed. DCE results showed that the treatment process attributes 'active listening' and 'time' were most relevant to all patients. Preferences for the attributes 'holistic treatment' (more relevant to the acupuncture and homeopathy groups) and 'information' (more relevant to the GM group) seemed to differ slightly between the groups. Willingness-to-pay values were higher in the acupuncture and homeopathy groups. CONCLUSIONS: The time physicians take and the extent to which they listen attentively are most important and are equally important to all patients. These results may contribute to the debate about more patient-centered healthcare. They support a strengthening of medical consultations in the German healthcare system. We suggest giving physicians the opportunity to spend more time with their patients, which may be achieved by changing the general conditions of remuneration (e.g., improved reimbursement of medical consultations). GERMAN CLINICAL TRIAL REGISTER: DRKS00013160.