Effects of Early Emollient Use in Children at High Risk of Atopic Dermatitis: A German Pilot Study.

Several small studies have indicated that daily emollient use from birth might delay, suppress or prevent atopic dermatitis (AD). Two larger trials did not confirm this; however, a recent smaller study indicated a protective effect if daily emollient use is used in the first 2 months of life. Further research is needed to evaluate the effect of emollient use on development of AD. The current study randomly assigned 50 newborns who were at high risk of developing AD (1:1) to receive general infant skin-care advice (control group), or skin-care advice plus emollient with advice to apply emollient at least once daily until 1 year of age (intervention group). Repeated skin examinations, skin physiology measurements and skin microbiome profiling were performed. Of the children in the intervention and control groups, 28% and 24%, respectively, developed AD (adjusted Relative Risk (RR) 1.19, p = 0.65, adjusted risk difference 0.05). Skin pH decreased and transepidermal water loss and stratum corneum hydration increased over time in both groups with no significant differences. In the intervention group skin microbiome alpha diversity increased earlier, and the abundance of Streptococcus and Staphylococcus species were significantly reduced at month 1. Daily early emollient use in children with high risk of AD was safe, but it did not significantly reduce the risk of developing AD or impact skin physiology development.

Implementing longitudinal integrated curricula: Systematic review of barriers and facilitators.

PURPOSE: The increase of longitudinal integrated curricula in medical schools worldwide represents the shift towards an outcome-oriented education. This novel model allows comprehensive student-patient interactions over time and integrates the educational content across disciplines. According to quantitative research, students, patients, doctors and communities benefit from this educational model in terms of participant satisfaction, learning outcomes and clinician recruitment. However, quantitative research does not provide detailed information on programme implementation processes. Therefore, this review aims to summarise facilitators and barriers of programme implementation reported in qualitative and mixed methods studies. METHOD: The authors reviewed the literature about facilitators and barriers for the implementation of longitudinal integrated curricula in undergraduate medical education programmes. The systematic search was conducted in MEDLINE, Embase and PsycINFO on 2 December 2019. The authors used the CASP checklist for qualitative research for the critical appraisal and summarised the results across studies using thematic content analysis. RESULTS: The authors screened 1682 reports. Twenty studies examining 17 different curricula met the inclusion criteria. Most curricula were implemented in the United States (n = 6/17), Australia (n = 5/17) or Canada (n = 4/17). Programme implementation is facilitated and hampered by its educational components (eg continuity of supervision, safe learning environments), organisational structures (eg community involvement) and participating students' and staff' motivation and personality. The critical appraisal revealed that several studies lacked transparent documentation and adequate reflection on the researcher-participant relationship (n = 20/20), data collection instruments (n = 12/20) and recruitment strategy (n = 4/20). CONCLUSIONS: The authors derived practical recommendations for the implementation of undergraduate, patient-centred, integrated medical curricula. Programme managers need to define and communicate common objectives with all participants. They should clarify the implementation of the objectives in all processes in a transparent and structured manner. Considering reporting guidelines, future studies in this field should document more transparently the methods used to gain qualitative insights and the researchers' personal involvement.

Impact of regionalisation and case-volume on neonatal and perinatal mortality: an umbrella review.

OBJECTIVE: This umbrella review summarises and critically appraises the evidence on the effects of regulated or high-volume perinatal care on outcome among very low birth weight/very preterm infants born in countries with neonatal mortality <5/1000 births. INTERVENTION/EXPOSITION: Perinatal regionalisation, centralisation, case-volume. PRIMARY OUTCOMES: Death. SECONDARY OUTCOMES: Disability, discomfort, disease, dissatisfaction. METHODS: On 29 November 2019 a systematic search in MEDLINE and Embase was performed and supplemented by hand search. Relevant systematic reviews (SRs) were critically appraised with A MeaSurement Tool to Assess systematic Reviews 2. RESULTS: The literature search revealed 508 hits and three SRs were included. Effects of perinatal regionalisation were assessed in three (34 studies) and case-volume in one SR (6 studies). Centralisation has not been evaluated. The included SRs reported effects on 'death' (eg, neonatal), 'disability' (eg, mental status), 'discomfort' (eg, maternal sensitivity) and 'disease' (eg, intraventricular haemorrhages). 'Dissatisfactions' were not reported. The critical appraisal showed a heterogeneous quality ranging from moderate to critically low. A pooled effect estimate was reported once and showed a significant favour of perinatal regionalisation in terms of neonatal mortality (OR 1.60, 95% CI 1.33-1.92). The qualitative evidence synthesis of the two SRs without pooled estimate suggests superiority of perinatal regionalisation in terms of different mortality and non-mortality outcomes. In one SR, contradictory results of lower neonatal mortality rates were reported in hospitals with higher birth volumes. CONCLUSIONS: Regionalised perinatal care seems to be a crucial care strategy to improve the survival of very low birth weight and preterm births. To overcome the low and critically low methodological quality and to consider additional clinical and patient-reported results that were not addressed by the SRs included, we recommend an updated SR. In the long term, an international, uniformly conceived and defined perinatal database could help to provide evidence-based recommendations on optimal strategies to regionalise perinatal care. PROSPERO REGISTRATION NUMBER: CRD42018094835.

Systemic Immunomodulatory Treatments for Patients With Atopic Dermatitis: A Systematic Review and Network Meta-analysis.

Importance: Most clinical trials assessing systemic immunomodulatory treatments for patients with atopic dermatitis are placebo-controlled. Objective: To compare the effectiveness and safety of systemic immunomodulatory treatments for patients with atopic dermatitis in a systematic review and network meta-analysis. Data Sources: The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Latin American and Caribbean Health Science Information database, Global Resource of Eczema Trials database, and clinical trial registries were searched from inception to October 28, 2019. Study Selection: English-language randomized clinical trials of 8 weeks or more of treatment with systemic immunomodulatory medications for moderate to severe atopic dermatitis were included. Titles, abstracts, and articles were screened in duplicate. Of 10 324 citations, 39 trials were included. Data Extraction and Synthesis: Data were extracted in duplicate, and the review adhered to Preferred Reporting Items for Systematic Reviews and Meta-analyses for Network Meta-Analyses guidelines. Random-effects bayesian network meta-analyses were performed and certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. Main Outcomes and Measures: Prespecified outcomes were change in signs of disease, symptoms, quality of life, itch, withdrawals, and serious adverse events. Results: A total of 39 trials with 6360 patients examining 20 medications and placebo were included. Most trials were conducted for adults receiving up to 16 weeks of therapy. Dupilumab, 300 mg every 2 weeks, was associated with improvement in the Eczema Area and Severity Index score vs placebo (mean difference, 11.3-point reduction; 95% credible interval [CrI], 9.7-13.1 [high certainty]). Cyclosporine (standardized mean difference, -1.1; 95% CrI, -1.7 to -0.5 [low certainty]) and dupilumab (standardized mean difference, -0.9; 95% CrI, -1.0 to -0.8 [high certainty]) were similarly effective vs placebo in clearing clinical signs of atopic dermatitis and may be superior to methotrexate (standardized mean difference, -0.6; 95% CrI, -1.1 to 0.0 [low certainty]) and azathioprine (standardized mean difference, -0.4; 95% CrI, -0.8 to -0.1 [low certainty]). Several investigational medications for atopic dermatitis are promising, but data to date are limited to small early-phase trials. Safety analyses were limited by low event rates. Conclusions and Relevance: Dupilumab and cyclosporine may be more effective for up to 16 weeks of treatment than methotrexate and azathioprine for treating adult patients with atopic dermatitis. More studies directly comparing established and novel treatments beyond 16 weeks are needed and will be incorporated into future updates of this review.

The moderating role of allergy immunotherapy in asthma progression: Results of a population-based cohort study.

BACKGROUND: Allergic asthma causes substantial morbidity and constitutes a public health burden, which increases with asthma severity. There is evidence that allergy immunotherapy (AIT) prevents the progression of allergic rhinitis (AR) to asthma. However, evidence is missing on the potential of AIT to prevent progression from milder to more severe asthma. METHODS: This population-based cohort study utilized healthcare data (2005 to 2014) from a statutory health insurance in Germany. The severity of asthma was classified according to the treatment steps recommended by the global initiative for asthma (GINA). The effect of AIT on the transition between the GINA steps was analyzed using multivariable Cox regression models adjusted for age and sex. RESULTS: From the total cohort of 1,739,440 patients, 39,167 individuals aged 14 years or older were classified as having incident asthma during the observation period and were included in the study. From these, 4111 patients (10.5%) received AIT. AIT exposure was associated with a significantly decreased likelihood of asthma progression from GINA step 1 to GINA step 3 (HR 0.87; 95% CI 0.80-0.95) and GINA step 3 to GINA step 4 (HR 0.66; 95% CI 0.60-0.74). GINA medication for step 2 and step 5 was rarely prescribed. CONCLUSIONS: This observational study in a real-world setting indicates that patients with allergic asthma who receive AIT are less likely to experience progression of asthma severity than asthma patients not receiving AIT.

Systemic immunomodulatory treatments for atopic dermatitis: protocol for a systematic review with network meta-analysis.

INTRODUCTION: There are numerous new systemic treatments for atopic dermatitis in various stages of development and most are being compared with placebo rather than active comparators. In order to understand the relative efficacy and safety of existing and new treatments for atopic dermatitis, robust mixed comparisons (ie, direct and indirect) would be beneficial. To address this gap, this protocol describes methods for a systematic review and network meta-analysis of systemic treatments for atopic dermatitis. METHODS AND ANALYSIS: We will update the search of a previous systematic review, including searches of the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Latin American and Caribbean Health Science Information database and the Global Resource of EczemA Trials database in addition to clinical trial protocol registries. Title, abstract and full paper screening as well as data extraction will be conducted in duplicate by independent researchers. Primary outcomes include efficacy with regards to clinician-reported signs and patient-reported symptoms and safety with regards to withdrawal from treatment due to adverse events and the occurrence of serious adverse events. Secondary outcomes will include change in quality of life and itch severity. Where possible and appropriate, network meta-analysis will be performed for each outcome using a random-effects model within a Bayesian framework. If appropriate, the review will be transitioned to a living review with continuous updating of the analysis. ETHICS AND DISSEMINATION: Dissemination in a peer-reviewed scientific journal is planned. PROSPERO REGISTRATION NUMBER: CRD42018088112; Pre-results.

The influence of cross-sectoral treatment models on patients with mental disorders in Germany: study protocol of a nationwide long-term evaluation study (EVA64).

BACKGROUND: Close, continuous and efficient collaboration between different professions and sectors of care is necessary to provide patient-centered care for individuals with mental disorders. The lack of structured collaboration between in- and outpatient care constitutes a limitation of the German health care system. Since 2012, a new law in Germany (§64b Social code book (SGB) V) has enabled the establishment of cross-sectoral and patient-centered treatment models in psychiatry. Such model projects follow a capitation budget, i.e. a total per patient budget of inpatient and outpatient care in psychiatric clinics. Providers are able to choose the treatment form and adapt the treatment to the needs of the patients. The present study (EVA64) will investigate the effectiveness, costs and efficiency of almost all model projects established in Germany between 2013 and 2016. METHODS/DESIGN: A health insurance data-based controlled cohort study is used. Data from up to 89 statutory health insurance (SHI) funds, i.e. 79% of all SHI funds in Germany (May 2017), on inpatient and outpatient care, pharmaceutical and non-pharmaceutical treatments and sick leave for a period of 7 years will be analyzed. All patients insured by any of the participating SHI funds and treated in one of the model hospitals for any of 16 pre-defined mental disorders will be compared with patients in routine care. Sick leave (primary outcome), utilization of inpatient care (primary outcome), utilization of outpatient care, continuity of contacts in (psychiatric) care, physician and hospital hopping, re-admission rate, comorbidity, mortality, disease progression, and guideline adherence will be analyzed. Cost and effectivity of model and routine care will be estimated using cost-effectiveness analyses. Up to 10 control hospitals for each of the 18 model hospitals will be selected according to a pre-defined algorithm. DISCUSSION: The evaluation of complex interventions is an important main task of health services research and constitutes the basis of evidence-guided advancement in health care. The study will yield important new evidence to guide the future provision of routine care for mentally ill patients in Germany and possibly beyond. TRIAL REGISTRATION: This study was registered in the database "Health Services Research Germany" (trial number: VVfD_EVA64_15_003713 ).

Health utilities for controlled and uncontrolled chronic hand eczema in healthcare employees.

BACKGROUND: Health utilities provide a universally applicable method for measuring the relative preferences or values of specific health states. Health economic studies use health utilities to estimate disease burden and the cost-effectiveness of interventions. Chronic hand eczema (CHE) affects many individuals and adversely affects work productivity. Health utilities for CHE from the perspective of healthcare professionals are lacking. OBJECTIVES: To assess health utilities for CHE from the perspectives of employees in the healthcare sector and affected patients. METHODS: A cross-sectional study with volunteers from the healthcare sector (n = 126) and patients (n = 32) was conducted to establish health utilities (ranging from 1 = perfect health to 0 = death) for mild and severe CHE. RESULTS: The median health utilities of the healthy volunteers derived with the time trade-off method were 0.97 (mean: 0.92) for mild CHE and 0.77 (mean: 0.75) for severe CHE. The median health utilities for mild and severe CHE from the perspective of affected patients were 0.98 (mean: 0.91) and 0.82 (mean: 0.77), respectively. Differences in health utilities between the two study groups were not significant. CONCLUSION: CHE constitutes a considerable burden from the perspective of healthcare employees. Effective control of CHE constitutes an important public health goal.

Therapy Decision Support Based on Recommender System Methods.

We present a system for data-driven therapy decision support based on techniques from the field of recommender systems. Two methods for therapy recommendation, namely, Collaborative Recommender and Demographic-based Recommender, are proposed. Both algorithms aim to predict the individual response to different therapy options using diverse patient data and recommend the therapy which is assumed to provide the best outcome for a specific patient and time, that is, consultation. The proposed methods are evaluated using a clinical database incorporating patients suffering from the autoimmune skin disease psoriasis. The Collaborative Recommender proves to generate both better outcome predictions and recommendation quality. However, due to sparsity in the data, this approach cannot provide recommendations for the entire database. In contrast, the Demographic-based Recommender performs worse on average but covers more consultations. Consequently, both methods profit from a combination into an overall recommender system.

Cost-effectiveness of systemic treatments for moderate-to-severe psoriasis in the German health care setting.

Systemic treatments of moderate-to-severe psoriasis differ substantially in terms of effectiveness and costs. Comprehensive economic-evaluations of all systemic treatments for psoriasis from a societal perspective are missing. The objective of our study was to compare the cost-effectiveness all systemic treatments approved for moderate-to-severe psoriasis from a societal perspective, by including all cost categories. An incremental cost-effectiveness-analysis was performed for all systemic treatments for psoriasis, currently recommended by the German S3-Guideline i.e. methotrexate, cyclosporine, fumaric acid esters, and retinoids, adalimumab, etanercept, infliximab and ustekinumab. We used a Markov model with time-dependent transition probabilities and a time horizon of 2 years to investigate incremental cost-effectiveness ratios. Both direct and indirect costs were considered to reflect the societal perspective. Effectiveness outcome was PASI-75 response. One-way and probabilistic sensitivity analyses explored the effect of treatment duration, discount rate, effectiveness, and the perspective (societal vs. healthcare system) on the findings. According to the base-case analysis a cost-effective treatment pathway for moderate-to-severe psoriasis starts with methotrexate, followed by ustekinumab 90 mg and infliximab, if methotrexate does not achieve or maintain PASI-75 response. Sensitivity analyses confirmed the general robustness of these findings with methotrexate being most cost-effective. However, from a third-party-payer perspective (without indirect cost) conventional therapies were generally more cost-effective than biologics. From a value-based healthcare perspective, methotrexate should be the systemic treatment of first choice, ustekinumab 90 mg second choice and infliximab third choice for patients with moderate-to-severe psoriasis. From a societal perspective, the other treatments are less efficient according to our model. From a third-party-payer perspective conventional therapies are more cost-effective than biologics.

Correlation between Dermatology Life Quality Index (DLQI) scores and Work Limitations Questionnaire (WLQ) allows the calculation of percent work productivity loss in patients with psoriasis.

Data on indirect costs are vital for cost-effectiveness studies from a societal perspective. In contrast to quality of life, information on productivity loss is rarely collected in psoriasis trials. We aimed to identify a model to deduce indirect costs (presenteeism and absenteeism) of psoriasis from the Dermatologic Life Quality Index (DLQI) of affected patients to facilitate health economic evaluations for psoriasis. We undertook a cross-sectional mapping study including 201 patients with physician-diagnosed psoriasis and investigated the relationship between quality of life (DLQI) and productivity loss (Work Limitations Questionnaire, WLQ--using the "output demands" subscale) using linear bootstrap regression analysis to set up an equation model allowing the calculation of percent work productivity loss per DLQI unit increase. DLQI and WLQ scores were significantly correlated (r = 0.47; p < 0.0001) The final equation model suggests a 0.545 and 0.560% decrease in productivity due to presenteeism and absenteeism per DLQI unit increase, with y-intercepts at 1.654 and 0.536, respectively. In the absence of data on indirect cost, work productivity loss due to psoriasis can be estimated from DLQI scores using the equations, Y = 0.545 × DLQI score + 1.654 for presenteeism (%) and Y = 0.560 × DLQI score + 0.536 for absenteeism (%).