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The selection of appropriate outcomes is crucial when designing clinical trials in order to compare the effects of different interventions directly. For the findings to influence policy and practice, the outcomes need to be relevant and important to key stakeholders including patients and the public, health care professionals and others making decisions about health care. It is now widely acknowledged that insufficient attention has been paid to the choice of outcomes measured in clinical trials. Researchers are increasingly addressing this issue through the development and use of a core outcome set, an agreed standardised collection of outcomes which should be measured and reported, as a minimum, in all trials for a specific clinical area.Accumulating work in this area has identified the need for guidance on the development, implementation, evaluation and updating of core outcome sets. This Handbook, developed by the COMET Initiative, brings together current thinking and methodological research regarding those issues. We recommend a four-step process to develop a core outcome set. The aim is to update the contents of the Handbook as further research is identified.

BACKGROUND: Biologics are used for the treatment of rheumatoid arthritis and many other conditions. While the efficacy of biologics has been established, there is uncertainty regarding the adverse effects of this treatment. Since serious risks such as tuberculosis (TB) reactivation, serious infections, and lymphomas may be common to the biologics but occur in small numbers across the various indications, we planned to combine the results from biologics used in many conditions to obtain the much needed risk estimates. OBJECTIVES: To compare the adverse effects of tumor necrosis factor blocker (etanercept, adalimumab, infliximab, golimumab, certolizumab), interleukin (IL)-1 antagonist (anakinra), IL-6 antagonist (tocilizumab), anti-CD28 (abatacept), and anti-B cell (rituximab) therapy in patients with any disease condition except human immunodeficiency disease (HIV/AIDS). METHODS: Randomized controlled trials (RCTs), controlled clinical trials (CCTs) and open-label extension (OLE) studies that studied one of the nine biologics for use in any indication (with the exception of HIV/AIDS) and that reported our pre-specified adverse outcomes were considered for inclusion. We searched The Cochrane Library, MEDLINE, and EMBASE (to January 2010). Identifying search results and data extraction were performed independently and in duplicate. For the network meta-analysis, we performed mixed-effects logistic regression using an arm-based, random-effects model within an empirical Bayes framework. MAIN RESULTS: We included 163 RCTs with 50,010 participants and 46 extension studies with 11,954 participants. The median duration of RCTs was six months and 13 months for OLEs. Data were limited for tuberculosis (TB) reactivation, lymphoma, and congestive heart failure. Adjusted for dose, biologics as a group were associated with a statistically significant higher rate of total adverse events (odds ratio (OR) 1.19, 95% CI 1.09 to 1.30; number needed to treat to harm (NNTH) = 30, 95% CI 21 to 60) and withdrawals due to adverse events (OR 1.32, 95% CI 1.06 to 1.64; NNTH = 37, 95% CI 19 to 190) and an increased risk of TB reactivation (OR 4.68, 95% CI 1.18 to 18.60; NNTH = 681, 95% CI 143 to 14706) compared to control.The rate of serious adverse events, serious infections, lymphoma, and congestive heart failure were not statistically significantly different between biologics and control treatment. Certolizumab pegol was associated with significantly higher risk of serious infections compared to control treatment (OR 3.51, 95% CI 1.59 to 7.79; NNTH = 17, 95% CI 7 to 68). Infliximab was associated with significantly higher risk of withdrawals due to adverse events compared to control (OR 2.04, 95% CI 1.43 to 2.91; NNTH = 12, 95% CI 8 to 28). Indirect comparisons revealed that abatacept and anakinra were associated with a significantly lower risk of serious adverse events compared to most other biologics. Although the overall numbers are relatively small, certolizumab pegol was associated with significantly higher odds of serious infections compared to etanercept, adalimumab, abatacept, anakinra, golimumab, infliximab, and rituximab; abatacept was significantly less likely than infliximab and tocilizumab to be associated with serious infections. Abatacept, adalimumab, etanercept and golimumab were significantly less likely than infliximab to result in withdrawals due to adverse events. AUTHORS' CONCLUSIONS: Overall, in the short term biologics were associated with significantly higher rates of total adverse events, withdrawals due to adverse events and TB reactivation. Some biologics had a statistically higher association with certain adverse outcomes compared to control, but there was no consistency across the outcomes so caution is needed in interpreting these results.There is an urgent need for more research regarding the long-term safety of biologics and the comparative safety of different biologics. National and international registries and other types of large databases are relevant sources for providing complementary evidence regarding the short- and longer-term safety of biologics.

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.

BACKGROUND: Core outcome sets (COS) can enhance the relevance of research by ensuring that outcomes of importance to health service users and other people making choices about health care in a particular topic area are measured routinely. Over 200 COS to date have been developed, but the clarity of these reports is suboptimal. COS studies will not achieve their goal if reports of COS are not complete and transparent. METHODS AND FINDINGS: In recognition of these issues, an international group that included experienced COS developers, methodologists, journal editors, potential users of COS (clinical trialists, systematic reviewers, and clinical guideline developers), and patient representatives developed the Core Outcome Set-STAndards for Reporting (COS-STAR) Statement as a reporting guideline for COS studies. The developmental process consisted of an initial reporting item generation stage and a two-round Delphi survey involving nearly 200 participants representing key stakeholder groups, followed by a consensus meeting. The COS-STAR Statement consists of a checklist of 18 items considered essential for transparent and complete reporting in all COS studies. The checklist items focus on the introduction, methods, results, and discussion section of a manuscript describing the development of a particular COS. A limitation of the COS-STAR Statement is that it was developed without representative views of low- and middle-income countries. COS have equal relevance to studies conducted in these areas, and, subsequently, this guideline may need to evolve over time to encompass any additional challenges from developing COS in these areas. CONCLUSIONS: With many ongoing COS studies underway, the COS-STAR Statement should be a helpful resource to improve the reporting of COS studies for the benefit of all COS users.

BACKGROUND: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes. METHODS & FINDINGS: Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 × 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI 0.55-0.74) of African American adults with T2D to remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants. CONCLUSIONS: As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.

To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.

BACKGROUND: Only a few telemedicine applications have made their way into regular care. One reason is the lack of acceptance of telemedicine by potential end users. OBJECTIVE: The aim of this systematic review was to identify theoretical predictors that influence the acceptance of telemedicine. METHODS: An electronic search was conducted in PubMed and PsycINFO in June 2018 and supplemented by a hand search. Articles were identified using predefined inclusion and exclusion criteria. In total, two reviewers independently assessed the title, abstract, and full-text screening and then individually performed a quality assessment of all included studies. RESULTS: Out of 5917 potentially relevant titles (duplicates excluded), 24 studies were included. The Axis Tool for quality assessment of cross-sectional studies revealed a high risk of bias for all studies except for one study. The most commonly used models were the Technology Acceptance Model (n=11) and the Unified Theory of Acceptance and Use of Technology (n=9). The main significant predictors of acceptance were perceived usefulness (n=11), social influences (n=6), and attitude (n=6). The results show a superiority of technology acceptance versus original behavioral models. CONCLUSIONS: The main finding of this review is the applicability of technology acceptance models and theories on telemedicine adoption. Characteristics of the technology, such as its usefulness, as well as attributes of the individual, such as his or her need for social support, inform end-user acceptance. Therefore, in the future, requirements of the target group and the group's social environment should already be taken into account when planning telemedicine applications. The results support the importance of theory-guided user-centered design approaches to telemedicine development.

BACKGROUND: Telemedicine is defined by three characteristics: (1) using information and communication technologies, (2) covering a geographical distance, and (3) involving professionals who deliver care directly to a patient or a group of patients. It is said to improve chronic care management and self-management in patients with chronic diseases. However, currently available guidelines for the care of patients with diabetes, hypertension, or dyslipidemia do not include evidence-based guidance on which components of telemedicine are most effective for which patient populations. OBJECTIVE: The primary aim of this study was to identify, synthesize, and critically appraise evidence on the effectiveness of telemedicine solutions and their components on clinical outcomes in patients with diabetes, hypertension, or dyslipidemia. METHODS: We conducted an umbrella review of high-level evidence, including systematic reviews and meta-analyses of randomized controlled trials. On the basis of predefined eligibility criteria, extensive automated and manual searches of the databases PubMed, EMBASE, and Cochrane Library were conducted. Two authors independently screened the studies, extracted data, and carried out the quality assessments. Extracted data were presented according to intervention components and patient characteristics using defined thresholds of clinical relevance. Overall certainty of outcomes was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. RESULTS: (>8%). Telemedicine was not found to have a significant and clinically meaningful impact on blood pressure. Only reviews or meta-analyses reporting lipid outcomes in patients with diabetes were found. GRADE assessment revealed that the overall quality of the evidence was low to very low. CONCLUSIONS: The results of this umbrella review indicate that telemedicine has the potential to improve clinical outcomes in patients with diabetes. Although subgroup-specific effectiveness rates favoring certain intervention and population characteristics were found, the low GRADE ratings indicate that evidence can be considered as limited. Future updates of clinical care and practice guidelines should carefully assess the methodological quality of studies and the overall certainty of subgroup-specific outcomes before recommending telemedicine interventions for certain patient populations.

BACKGROUND: Although most patients with atopic dermatitis (AD) are effectively managed with topical medication, a significant minority require systemic therapy. Guidelines for decision making about advancement to systemic therapy are lacking. OBJECTIVE: To guide those considering use of systemic therapy in AD and provide a framework for evaluation before making this therapeutic decision with the patient. METHODS: A subgroup of the International Eczema Council determined aspects to consider before prescribing systemic therapy. Topics were assigned to expert reviewers who performed a topic-specific literature review, referred to guidelines when available, and provided interpretation and expert opinion. RESULTS: We recommend a systematic and holistic approach to assess patients with severe signs and symptoms of AD and impact on quality of life before systemic therapy. Steps taken before commencing systemic therapy include considering alternate or concomitant diagnoses, avoiding trigger factors, optimizing topical therapy, ensuring adequate patient/caregiver education, treating coexistent infection, assessing the impact on quality of life, and considering phototherapy. LIMITATIONS: Our work is a consensus statement, not a systematic review. CONCLUSION: The decision to start systemic medication should include assessment of severity and quality of life while considering the individual's general health status, psychologic needs, and personal attitudes toward systemic therapies.

BACKGROUND: Consensus-orientated Delphi studies are increasingly used in various areas of medical research using a variety of different rating scales and criteria for reaching consensus. We explored the influence of using three different rating scales and different consensus criteria on the results for reaching consensus and assessed the test-retest reliability of these scales within a study aimed at identification of global treatment goals for total knee arthroplasty (TKA). METHODS: We conducted a two-stage study consisting of two surveys and consecutively included patients scheduled for TKA from five German hospitals. Patients were asked to rate 19 potential treatment goals on different rating scales (three-point, five-point, nine-point). Surveys were conducted within a 2 week period prior to TKA, order of questions (scales and treatment goals) was randomized. RESULTS: Eighty patients (mean age 68 ± 10 years; 70% females) completed both surveys. Different rating scales (three-point, five-point and nine-point rating scale) lead to different consensus despite moderate to high correlation between rating scales (r = 0.65 to 0.74). Final consensus was highly influenced by the choice of rating scale with 14 (three-point), 6 (five-point), 15 (nine-point) out of 19 treatment goals reaching the pre-defined 75% consensus threshold. The number of goals reaching consensus also highly varied between rating scales for other consensus thresholds. Overall, concordance differed between the three-point (percent agreement [p] = 88.5%, weighted kappa [k] = 0.63), five-point (p = 75.3%, k = 0.47) and nine-point scale (p = 67.8%, k = 0.78). CONCLUSION: This study provides evidence that consensus depends on the rating scale and consensus threshold within one population. The test-retest reliability of the three rating scales investigated differs substantially between individual treatment goals. This variation in reliability can become a potential source of bias in consensus studies. In our setting aimed at capturing patients' treatment goals for TKA, the three-point scale proves to be the most reasonable choice, as its translation into the clinical context is the most straightforward among the scales. Researchers conducting Delphi studies should be aware that final consensus is substantially influenced by the choice of rating scale and consensus criteria.

The use of nonstandardized and inadequately validated outcome measures in atopic eczema trials is a major obstacle to practising evidence-based dermatology. The Harmonising Outcome Measures for Eczema (HOME) initiative is an international multiprofessional group dedicated to atopic eczema outcomes research. In June 2011, the HOME initiative conducted a consensus study involving 43 individuals from 10 countries, representing different stakeholders (patients, clinicians, methodologists, pharmaceutical industry) to determine core outcome domains for atopic eczema trials, to define quality criteria for atopic eczema outcome measures and to prioritize topics for atopic eczema outcomes research. Delegates were given evidence-based information, followed by structured group discussion and anonymous consensus voting. Consensus was achieved to include clinical signs, symptoms, long-term control of flares and quality of life into the core set of outcome domains for atopic eczema trials. The HOME initiative strongly recommends including and reporting these core outcome domains as primary or secondary endpoints in all future atopic eczema trials. Measures of these core outcome domains need to be valid, sensitive to change and feasible. Prioritized topics of the HOME initiative are the identification/development of the most appropriate instruments for the four core outcome domains. HOME is open to anyone with an interest in atopic eczema outcomes research.

BACKGROUND: The Harmonising Outcome Measures for Eczema (HOME) initiative has defined four core outcome domains for a core outcome set (COS) to be measured in all atopic eczema (AE) trials to ensure cross-trial comparison: clinical signs, symptoms, quality of life and long-term control. OBJECTIVES: The aim of this paper is to report on the consensus process that was used to select the core instrument to consistently assess symptoms in all future AE trials. METHODS: Following the HOME roadmap, two systematic reviews were performed which identified three instruments that had sufficient evidence of validity, reliability and feasibility to be considered for the final COS. RESULTS: At the fourth international HOME meeting, there was broad consensus among all stakeholders that the Patient-Oriented Eczema Measure (POEM) should be used as the core instrument (87·5% agreed, 9·4% unsure, 3·1% disagreed). CONCLUSIONS: All relevant stakeholders are encouraged to use POEM as the chosen instrument to measure the core domain of symptoms in all future AE clinical trials. Other instruments of interest can be used in addition to POEM.

BACKGROUND: It is not known whether modern volatile anesthetics are associated with less mortality and postoperative pulmonary or other complications in patients undergoing general anesthesia for surgery. METHODS: A systematic literature review was conducted for randomized controlled trials fulfilling following criteria: (1) population: adult patients undergoing general anesthesia for surgery; (2) intervention: patients receiving sevoflurane, desflurane, or isoflurane; (3) comparison: volatile anesthetics versus total IV anesthesia or volatile anesthetics; (4) reporting on: (a) mortality (primary outcome) and (b) postoperative pulmonary or other complications; (5) study design: randomized controlled trials. The authors pooled treatment effects following Peto odds ratio (OR) meta-analysis and network meta-analysis methods. RESULTS: Sixty-eight randomized controlled trials with 7,104 patients were retained for analysis. In cardiac surgery, volatile anesthetics were associated with reduced mortality (OR = 0.55; 95% CI, 0.35 to 0.85; P = 0.007), less pulmonary (OR = 0.71; 95% CI, 0.52 to 0.98; P = 0.038), and other complications (OR = 0.74; 95% CI, 0.58 to 0.95; P = 0.020). In noncardiac surgery, volatile anesthetics were not associated with reduced mortality (OR = 1.31; 95% CI, 0.83 to 2.05, P = 0.242) or lower incidences of pulmonary (OR = 0.67; 95% CI, 0.42 to 1.05; P = 0.081) and other complications (OR = 0.70; 95% CI, 0.46 to 1.05; P = 0.092). CONCLUSIONS: In cardiac, but not in noncardiac, surgery, when compared to total IV anesthesia, general anesthesia with volatile anesthetics was associated with major benefits in outcome, including reduced mortality, as well as lower incidence of pulmonary and other complications. Further studies are warranted to address the impact of volatile anesthetics on outcome in noncardiac surgery.

OBJECTIVE: Osteoarthritis (OA) is highly prevalent throughout the world, especially in the elderly population, and is strongly associated with patients' frailty. However, little is known about the prevalence and treatment of OA in elderly patients in routine clinical care in Germany. MATERIALS AND METHODS: As a part of Linking Patient-Reported Outcomes with CLAIms Data for Health Services Research in Rheumatology (PROCLAIR), a cross-sectional study using claims data from a large Germany statutory health insurance (BARMER) was conducted. We included people aged 60 years or older and assessed the prevalence of OA of the hip or knee, defined as having outpatient diagnoses (ICD: M16 or M17) in at least two quarters of 2014. The use of conservative treatment, including analgesics and physical therapy, and total joint replacement was studied. Analyses were stratified by age, sex, comorbidities, and level of care dependency defined by social law. RESULTS: A total of 595,754 patients (mean age: 74.9 years; 69.8% female) were diagnosed with OA (21.8%), with the highest prevalence in those between 80 and 89 years (31.0%) and in females compared to males (23.9% vs 18.3%). Prevalence decreased with increasing level of care dependency from 30.5% in patients with a low level (0/1) to 18.7% in the highest level of care dependency. A total of 63.4% of the patients with OA received analgesics, with higher use with increasing age. Physical therapy was prescribed to 43.1% of the patients, but use decreased with age. In all, 5.3% of the patients received total joint replacement in 2014. CONCLUSION: The lower frequency of coded OA with increasing level of care dependency may reflect underdiagnosis, and patients with many other medical problems seem to be at risk for inadequate recognition and treatment of their OA.

As of late 2019, the COVID-19 pandemic has been a challenge to health care systems worldwide. Rapidly rising local COVID-19 incidence rates, result in demand for high hospital and intensive care bed capacities on short notice. A detailed up-to-date regional surveillance of the dynamics of the pandemic, precise prediction of required inpatient capacities of care as well as a centralized coordination of the distribution of regional patient fluxes is needed to ensure optimal patient care. In March 2020, the German federal state of Saxony established three COVID-19 coordination centers located at each of its maximum care hospitals, namely the University Hospitals Dresden and Leipzig and the hospital Chemnitz. Each center has coordinated inpatient care facilities for the three regions East, Northwest and Southwest Saxony with 36, 18 and 29 hospital sites, respectively. Fed by daily data flows from local public health authorities capturing the dynamics of the pandemic as well as daily reports on regional inpatient care capacities, we established the information and prognosis tool DISPENSE. It provides a regional overview of the current pandemic situation combined with daily prognoses for up to seven days as well as outlooks for up to 14 days of bed requirements. The prognosis precision varies from 21% and 38% to 12% and 15% relative errors in normal ward and ICU bed demand, respectively, depending on the considered time period. The deployment of DISPENSE has had a major positive impact to stay alert for the second wave of the COVID-19 pandemic and to allocate resources as needed. The application of a mathematical model to forecast required bed capacities enabled concerted actions for patient allocation and strategic planning. The ad-hoc implementation of these tools substantiates the need of a detailed data basis that enables appropriate responses, both on regional scales in terms of clinic resource planning and on larger scales concerning political reactions to pandemic situations.

BACKGROUND: While different proposals exist for a guideline on reporting Delphi studies, none of them has yet established itself in the health and social sciences and across the range of Delphi variants. This seems critical because empirical studies demonstrate a diversity of modifications in the conduction of Delphi studies and sometimes even errors in the reporting. The aim of the present study is to close this gap and formulate a general reporting guideline. METHOD: In an international Delphi procedure, Delphi experts were surveyed online in three rounds to find consensus on a reporting guideline for Delphi studies in the health and social sciences. The respondents were selected via publications of Delphi studies. The preliminary reporting guideline, containing 65 items on five topics and presented for evaluation, had been developed based on a systematic review of the practice of Delphi studies and a systematic review of existing reporting guidelines for Delphi studies. Starting in the second Delphi round, the experts received feedback in the form of mean values, measures of dispersion, a summary of the open-ended responses and their own response in the previous round. The final draft of the reporting guideline contains the items on which at least 75% of the respondents agreed by assigning scale points 6 and 7 on a 7-point Likert scale. RESULTS: 1,072 experts were invited to participate. A total of 91 experts completed the first Delphi round, 69 experts the second round, and 56 experts the third round. Of the 65 items in the first draft of the reporting guideline, consensus was ultimately reached for 38 items addressing the five topics: Title and Abstract (n = 3), Context (n = 7), Method (n = 20), Results (n = 4) and Discussion (n = 4). Items focusing on theoretical research and on dissemination were either rejected or remained subjects of dissent. DISCUSSION: We assume a high level of acceptance and interdisciplinary suitability regarding the reporting guideline presented here and referred to as the "Delphi studies in social and health sciences-recommendations for an interdisciplinary standardized reporting" (DELPHISTAR). Use of this reporting guideline can substantially improve the ability to compare and evaluate Delphi studies.

Importance: Systemic treatments for atopic dermatitis are being evaluated primarily in placebo-controlled trials; network meta-analysis can provide relative efficacy and safety estimates for treatments that have not been compared head to head. Objective: To compare reported measures of efficacy and assessments of safety in clinical trials of systemic treatments for atopic dermatitis in a living 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 trial registries were searched through June 15, 2021. Study Selection: Randomized clinical trials examining 8 or more weeks of treatment with systemic immunomodulatory medications for moderate-to-severe atopic dermatitis were included after screening titles, abstracts, and papers in duplicate. Data Extraction and Synthesis: Data were abstracted in duplicate. Bayesian network meta-analyses and assessed Grading of Recommendations Assessment, Development and Evaluation certainty of evidence were performed. The updated analysis was completed from June to December 2021. Main Outcomes and Measures: Outcomes include change in Eczema Area and Severity Index (EASI), Patient Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), and Peak Pruritus Numeric Rating Scales (PP-NRS). Results: Since October 2019, 21 new studies were added, for a total of 60 trials with 16 579 patients. Up to 16 weeks of treatment in adults, abrocitinib, 200 mg daily (mean difference [MD], 2.2; 95% credible interval [CrI], 0.2-4.0; high certainty) and upadacitinib, 30 mg daily (MD, 2.7; 95% CrI, 0.6-4.7; high certainty) were associated with reduced EASI slightly more than dupilumab, 600 mg then 300 mg every 2 weeks. Abrocitinib, 100 mg daily (MD, -2.1; 95% CrI, -4.1 to -0.3; high certainty), baricitinib, 4 mg daily (MD, -3.2; 95% CrI, -5.7 to -0.8; high certainty), baricitinib, 2 mg daily (MD, -5.2; 95% CrI, -7.5 to -2.9; high certainty) and tralokinumab, 600 mg then 300 mg every 2 weeks (MD, -3.5; 95% CrI, -5.8 to -1.3; high certainty) were associated with reduced EASI slightly less than dupilumab. There was little or no difference between upadacitinib, 15 mg daily, and dupilumab (MD, 0.2; 95% CrI, -1.9 to 2.2; high certainty). The pattern of results was similar for POEM, DLQI, and PP-NRS. Conclusions and Relevance: In this systematic review and meta-analysis, abrocitinib, 200 mg; and upadacitinib, 30 mg daily, were associated with slightly better scores than dupilumab, and upadacitinib, 15 mg daily, was associated with similar scores to dupilumab. Abrocitinib, 100 mg daily, baricitinib, 4 mg and 2 mg daily, and tralokinumab, 300 mg, every 2 weeks were associated with slightly worse scores.

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.

Core outcome sets are critically important outcomes that should be measured in clinical trials. Their absence in atopic dermatitis is a form of research waste and impedes combining evidence to inform patient care. Here, we articulate the rationale for core outcome sets in atopic dermatitis and review the work of the international Harmonising Outcome Measures for Eczema group from its inception in Munich, 2010. We describe core domain determination (what should be measured), to instrument selection (how domains should be measured), culminating in the complete core outcome measurement set in Tokyo, 2019. Using a "road map," Harmonising Outcome Measures for Eczema includes diverse research methods including Delphi and nominal group techniques informed by systematic reviews of properties of candidate instruments. The 4 domains and recommended instruments for including in all clinical trials of atopic dermatitis are patient symptoms, measured by Patient-Oriented Eczema Measure and peak Numerical Rating Scale 11 for itch intensity over 24 hours, clinical signs measured using the Eczema Area and Severity Index, quality of life measured by the Dermatology Life Quality Index series for adults, children, and infants, and long-term control measured by either Recap of atopic eczema or Atopic Dermatitis Control Tool.

Although secondary data analyses have been established in recent years in health research, explicit recommendations for standardized, transparent and complete reporting of secondary data analyses do not exist as yet. Therefore, between 2009 and 2014, a first proposal for a specific reporting standard for secondary data analysis was developed (STROSA 1). Parallel to this national process in Germany, an international reporting standard for routine data analysis was initiated in 2013 (RECORD). Nevertheless, because of the specific characteristics of the German health care system as well as specific data protection requirements, the need for a specific German reporting standard for secondary data analyses became evident. Therefore, STROSA was revised and tested by a task force of 15 experts from the working group Collection and Use of Secondary Data (AGENS) of the German Society for Social Medicine and Prevention (DGSMP) and the German Society for Epidemiology (DGEpi) as well as from the working group Validation and Linkage of Secondary Data of the German Network for Health Services Research (DNVF). The consensus STROSA-2 checklist includes 27 criteria, which should be met in the reporting of secondary data analysis from Germany. The criteria have been illustrated and clarified with specific explanations and examples of good practice. The STROSA reporting standard aims at stimulating a wider scientific discussion on the practicability and completeness of the checklist. After further discussions and possibly resulting modifications, STROSA shall be implemented as a reporting standard for secondary data analyses from Germany. This will guarantee standardized and complete information on secondary data analyses enabling assessment of their internal and external validity.