S3 Guideline Atopic dermatitis: Part 1 - General aspects, topical and non-drug therapies, special patient groups.

This S3 guideline was created based on the European S3 guideline, with special consideration of the medical conditions in the German-speaking region and incorporating additions from the previous German-language version. The interdisciplinary guideline commission consisted of representatives from the German Dermatological Society, the Professional Association of German Dermatologists, the Austrian Society of Dermatology and Venereology, the Swiss Society of Dermatology and Venereology, the German Society for Allergology and Clinical Immunology, the German Society for Pediatric and Adolescent Medicine, the Professional Association of Pediatricians and Adolescent Medicine, the Society for Pediatric Allergology and Environmental Medicine, the German Society for Pediatric Rehabilitation and Prevention, the German Society for Psychosomatic Medicine and Medical Psychotherapy, the German Network for Health Services Research, the German Eczema Association and the German Allergy and Asthma Association. This first part of the guideline focuses on the definition and diagnostic aspects of atopic dermatitis (AD), addressing topical therapy as well as non-pharmacological treatment approaches such as UV therapy, psychoeducational therapy, dietary interventions for AD, allergen immunotherapy for AD, and complementary medicine. This part of the guideline also covers specific aspects of AD in children and adolescents, during pregnancy and lactation, and in the context of family planning. Additionally, it addresses occupational aspects of AD and highlights the perspective of the patients. The second part of the guideline, published separately, addresses the systemic therapy of AD.

Socioeconomic differences in the utilization of diagnostic imaging and non-pharmaceutical conservative therapies for spinal diseases.

BACKGROUND: A different utilization of health care services due to socioeconomic status on the same health plan contradicts the principle of equal treatment. We investigated the presence and magnitude of socioeconomic differences in utilization of diagnostic imaging and non-pharmaceutical conservative therapies for patients with spinal diseases. METHODS: The cohort study based on routine healthcare data from Germany with 11.7 million patient-years between 2012 and 2016 for patients with physician-confirmed spinal diseases (ICD-10: M40-M54), occupation and age 20 to 64 years. A Poisson model estimated the effects of the socioeconomic status (school education, professional education and occupational position) for the risk ratio of receiving diagnostic imaging (radiography, computed tomography, magnetic resonance imaging) and non-pharmaceutical conservative therapies (physical therapy including exercise therapy, manual therapy and massage, spinal manipulative therapy, acupuncture). RESULTS: Patients received diagnostic imaging in 26%, physical therapy in 32%, spinal manipulative therapy in 25%, and acupuncture in 4% of all patient-years. Similar to previous survey-based studies higher rates of utilization were associated with higher socioeconomic status. These differences were most pronounced for manual therapy, exercise therapy, and magnetic resonance imaging. CONCLUSIONS: The observed differences in health care utilization were highly related to socioeconomic status. Socioeconomic differences were higher for more expensive health services. Further research is necessary to identify barriers to equitable access to health services and to take appropriate action to decrease existing social disparities.

Lack of Harmonized Adherence Criteria in Allergen Immunotherapy Prevents Comparison of Dosing and Application Strategies: A Scoping Review.

Allergen immunotherapy (AIT) involves the application of increasing doses of allergen extract (as oral, sublingual, or subcutaneous immunotherapy) until immunologic tolerance is reached. Successful AIT relies on the consistent administration of allergen extract; therefore, adherence to these treatments is vital for compelling long-term results. Our review discusses the current terminology from adherence research in general, summarizes 25 current studies on adherence research in AIT in a scoping literature review, and delineates recommendations for tools and parameters for adherence research, aiming to improve outcomes in AIT. Almost every adherence study in AIT published to date used different tools, parameters, and data sources for measuring adherence and persistence rates. Unfortunately, an easily accessible, objective parameter or biomarker for monitoring treatment adherence and success has not yet been established for AIT. This situation calls for the development of an international core outcomes set for AIT that defines what is exactly meant by AIT adherence and how AIT adherence should be consistently measured. Therefore, we exemplarily present results and conclusions from adherence research in chronic diseases other than allergology. We aim to facilitate the development of advanced methods, considering the challenging disease specificities of these parameters in a routine care setting of AIT.

Mapping exercise and status update of eight established registries within the TREatment of ATopic eczema Registry Taskforce.

BACKGROUND: The TREatment of ATopic eczema (TREAT) Registry Taskforce is a collaborative international network of registries collecting data of atopic eczema (AE) patients receiving systemic and phototherapy with the common goal to provide long-term real-world data on the effectiveness, safety and cost-effectiveness of therapies. A core dataset, consisting of domains and domain items with corresponding measurement instruments, has been developed to harmonize data collection. OBJECTIVES: We aimed to give an overview of the status and characteristics of the eight established TREAT registries, and to perform a mapping exercise to examine the degree of overlap and pooling ability between the national registry datasets. This will allow us to determine which research questions can be answered in the future by pooling data. METHODS: All eight registries were asked to share their dataset and information on the current status and characteristics. The overlap between the core dataset and each registry dataset was identified (according to the domains, domain items and measurement instruments of the TREAT core dataset). RESULTS AND CONCLUSIONS: A total of 4702 participants have been recruited in the eight registries as of 1st of May 2022. Of the 69 core dataset domain items, data pooling was possible for 69 domain item outcomes in TREAT NL (the Netherlands), 61 items in A-STAR (UK and Ireland), 38 items in TREATgermany (Germany), 36 items in FIRST (France), 33 items in AtopyReg (Italy), 29 items in Biobadatop (Spain), 28 items in SCRATCH (Denmark) and 20 items in SwedAD (Sweden). Pooled analyses across all registries can be performed on multiple important domain items, covering the main aims of analysing data on the (cost-)effectiveness and safety of AE therapies. These results will facilitate future comparative or joint analyses.

Evaluation of a flexible and integrative psychiatric care model in a department of child and adolescent psychiatry in Tübingen, Germany: study protocol (EVA_TIBAS).

BACKGROUND: Model projects for flexible and integrated treatment (FIT) in Germany aim at advancing the quality of care for people with mental disorders. A new FIT model project was established in 2017 at the Department of child and adolescent psychiatry (KJP) of the University Hospital Tübingen (Universitätsklinikum Tübingen, UKT). The study design of EVA_TIBAS presented here describes the evaluation of the FIT model project at the KJP of the UKT. This evaluation aims at quantifying the anticipated FIT model project changes, which are to improve patients' cross-sectoral care at the same maximum cost as standard care. METHODS: EVA_TIBAS is a controlled cohort study using a mix of quantitative and qualitative methods. The FIT evaluation consists of three modules. In Module A, anonymized claims data of a statutory health insurance fund will be used to compare outcomes (duration of inpatient and day care psychiatric treatment, inpatient and day care psychiatric length of stay, outpatient psychiatric treatment in hospital, inpatient hospital readmission, emergency admission rate, direct medical costs) of patients treated in the model hospital with patients treated in structurally comparable control hospitals (estimated sample size = ca. 600 patients). In Module B, patient-reported outcomes (health related quality of life, symptom burden, return to psychosocial relationships (e.g. school, friends, hobbies), treatment satisfaction, societal costs) will be assessed quantitatively using validated questionnaires for the model and two control hospitals (estimated sample size = ca. 300 patients). A subsequent health economic evaluation will be based on cost-effectiveness analyses from both the insurance fund's and the societal perspective. In Module C, about 30 semi-structured interviews will examine the quality of offer, effects and benefits of the service offered by the social service of the AOK Baden-Württemberg (for stabilizing the overall situation of care in the family) in the model hospital. A focus group discussion will address the quality of cooperation between employees of the university hospital and the social services. DISCUSSION: The results of this evaluation will be used to inform policy makers whether this FIT model project or aspects of it should be implemented into standard care. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov PRS (ID: NCT04727359 , date: 27 January 2021).

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.

Interventions for mycosis fungoides.

BACKGROUND: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available, which may induce clinical remission for a time. This is an update of a Cochrane Review first published in 2012: we wanted to assess new trials, some of which investigated new interventions. OBJECTIVES: To assess the effects of interventions for MF in all stages of the disease. SEARCH METHODS: We updated our searches of the following databases to May 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched 2 trials registries for additional references. For adverse event outcomes, we undertook separate searches in MEDLINE in April, July and November 2017. SELECTION CRITERIA: Randomised controlled trials (RCTs) of local or systemic interventions for MF in adults with any stage of the disease compared with either another local or systemic intervention or with placebo. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The primary outcomes were improvement in health-related quality of life as defined by participants, and common adverse effects of the treatments. Key secondary outcomes were complete response (CR), defined as complete disappearance of all clinical evidence of disease, and objective response rate (ORR), defined as proportion of patients with a partial or complete response. We used GRADE to assess the certainty of evidence and considered comparisons of psoralen plus ultraviolet A (PUVA) light treatment as most important because this is first-line treatment for MF in most guidelines. MAIN RESULTS: This review includes 20 RCTs (1369 participants) covering a wide range of interventions. The following were assessed as either treatments or comparators: imiquimod, peldesine, hypericin, mechlorethamine, nitrogen mustard and intralesional injections of interferon-α (IFN-α) (topical applications); PUVA, extracorporeal photopheresis (ECP: photochemotherapy), and visible light (light applications); acitretin, bexarotene, lenalidomide, methotrexate and vorinostat (oral agents); brentuximab vedotin; denileukin diftitox; mogamulizumab; chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine; a combination of chemotherapy with electron beam radiation; subcutaneous injection of IFN-α; and intramuscular injections of active transfer factor (parenteral systemics). Thirteen trials used an active comparator, five were placebo-controlled, and two compared an active operator to observation only. In 14 trials, participants had MF in clinical stages IA to IIB. All participants were treated in secondary and tertiary care settings, mainly in Europe, North America or Australia. Trials recruited both men and women, with more male participants overall. Trial duration varied from four weeks to 12 months, with one longer-term study lasting more than six years. We judged 16 trials as at high risk of bias in at least one domain, most commonly performance bias (blinding of participants and investigators), attrition bias and reporting bias. None of our key comparisons measured quality of life, and the two studies that did presented no usable data. Eighteen studies reported common adverse effects of the treatments. Adverse effects ranged from mild symptoms to lethal complications depending upon the treatment type. More aggressive treatments like systemic chemotherapy generally resulted in more severe adverse effects. In the included studies, CR rates ranged from 0% to 83% (median 31%), and ORR ranged from 0% to 88% (median 47%). Five trials assessed PUVA treatment, alone or combined, summarised below. There may be little to no difference between intralesional IFN-α and PUVA compared with PUVA alone for 24 to 52 weeks in CR (risk ratio (RR) 1.07, 95% confidence interval (CI) 0.87 to 1.31; 2 trials; 122 participants; low-certainty evidence). Common adverse events and ORR were not measured. One small cross-over trial found once-monthly ECP for six months may be less effective than twice-weekly PUVA for three months, reporting CR in two of eight participants and ORR in six of eight participants after PUVA, compared with no CR or ORR after ECP (very low-certainty evidence). Some participants reported mild nausea after PUVA but no numerical data were given. One participant in the ECP group withdrew due to hypotension. However, we are unsure of the results due to very low-certainty evidence. One trial comparing bexarotene plus PUVA versus PUVA alone for up to 16 weeks reported one case of photosensitivity in the bexarotene plus PUVA group compared to none in the PUVA-alone group (87 participants; low-certainty evidence). There may be little to no difference between bexarotene plus PUVA and PUVA alone in CR (RR 1.41, 95% CI 0.71 to 2.80) and ORR (RR 0.94, 95% CI 0.61 to 1.44) (93 participants; low-certainty evidence). One trial comparing subcutaneous IFN-α injections combined with either acitretin or PUVA for up to 48 weeks or until CR indicated there may be little to no difference in the common IFN-α adverse effect of flu-like symptoms (RR 1.32, 95% CI 0.92 to 1.88; 82 participants). There may be lower CR with IFN-α and acitretin compared with IFN-α and PUVA (RR 0.54, 95% CI 0.35 to 0.84; 82 participants) (both outcomes: low-certainty evidence). This trial did not measure ORR. One trial comparing PUVA maintenance treatment to no maintenance treatment, in participants who had already had CR, did report common adverse effects. However, the distribution was not evaluable. CR and OR were not assessable. The range of treatment options meant that rare adverse effects consequently occurred in a variety of organs. AUTHORS' CONCLUSIONS: ​​There is a lack of high-certainty evidence to support decision making in the treatment of MF. Because of substantial heterogeneity in design, missing data, small sample sizes, and low methodological quality, the comparative safety and efficacy of these interventions cannot be reliably established on the basis of the included RCTs. PUVA is commonly recommended as first-line treatment for MF, and we did not find evidence to challenge this recommendation. There was an absence of evidence to support the use of intralesional IFN-α or bexarotene in people receiving PUVA and an absence of evidence to support the use of acitretin or ECP for treating MF. Future trials should compare the safety and efficacy of treatments to PUVA, as the current standard of care, and should measure quality of life and common adverse effects.

Chronic hand eczema in Germany: 5-year follow-up data from the CARPE registry.

BACKGROUND: The CARPE registry was set up in 2009 to prospectively investigate the management of patients with chronic hand eczema (CHE). OBJECTIVES: To report comprehensive follow-up data from the CARPE registry. PATIENTS AND METHODS: We investigated sociodemographic and clinical characteristics, provision of medical care, physician-assessed outcomes, and patient-reported outcomes (PROs). Data were collected between 2009 and 2016, with up to 5 years of follow-up, and are reported descriptively. RESULTS: Overall, 1281 patients were included in the registry (53.7% female). Mean age was 47.0 years. Of the patients, 793 and 231 completed the 2-year follow-up and 5-year follow-up, respectively. At baseline, 5.4% had changed or given up their job because of CHE, the average duration of CHE was 6.1 years, and, in 22.4%, the CHE was severe according to physician global assessment. Systemic treatment (alitretinoin, acitretin, and methotrexate) was prescribed at least once to 39.0% of the patients during the course of the follow-up. Disease severity, quality of life and treatment satisfaction improved over time, and the proportion of patients receiving systemic treatments decreased. CONCLUSIONS: Under continued dermatological care, substantial improvements in disease severity and PROs over time was achieved during the course of the CARPE registry, even in patients with long-standing and severe hand eczema.

Indication Criteria for Total Knee Arthroplasty in Patients with Osteoarthritis - A Multi-perspective Consensus Study.

Background and Objectives Knee osteoarthritis (OA) is a significant public health burden. Rates of total knee arthroplasty (TKA) in OA vary substantially between geographical regions, most likely due to the lack of standardised indication criteria. We set out to define indication criteria for the German healthcare system for TKA in patients with knee OA, on the basis of best evidence and transparent multi-stakeholder consensus. Methods We undertook a complex mixed methods study, including an iterative process of systematic appraisal of existing evidence, Delphi consensus methods and stakeholder conferences. We established a consensus panel representing key German national societies of healthcare providers (orthopaedic surgeons, rheumatologists, pain physicians, psychologists, physiotherapists), payers, and patient representatives. A priori defined consensus criteria were at least 70% agreement and less than 20% disagreement among the consensus panel. Agreement was sought for (1) core indication criteria defined as criteria that must be met to consider TKA in a normal patient with knee OA, (2) additional (not obligatory) indication criteria, (3) absolute contraindication criteria that generally prohibit TKA, and (4) risk factors that do not prohibit TKA, but usually do not lead to a recommendation for TKA. Results The following 5 core indication criteria were agreed within the panel: 1. intermittent (several times per week) or constant knee pain for at least 3 - 6 months; 2. radiological confirmation of structural knee damage (osteoarthritis, osteonecrosis); 3. inadequate response to conservative treatment, including pharmacological and non-pharmacological treatment for at least 3 - 6 months; 4. adverse impact of knee disease on patient's quality of life for at least 3 - 6 months; 5. patient-reported suffering/impairment due to knee disease. Additional indication criteria, contraindication criteria, and risk factors for adverse outcome were also agreed by a large majority within the multi-perspective stakeholder panel. Conclusion The defined indication criteria constitute a prerequisite for appropriate provision of TKA in patients with knee OA in Germany. In eligible patients, shared-decision making should eventually determine if TKA is performed or not. The next important steps are the implementation of the defined indication criteria, and the prospective investigation of predictors of success or failure of TKA in the context of routine care provision in Germany.

When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council.

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.

"Allergic mood" - Depressive and anxiety symptoms in patients with seasonal allergic rhinitis (SAR) and their association to inflammatory, endocrine, and allergic markers.

A growing number of studies show an association between seasonal allergic rhinitis (SAR) with depression and anxiety. The underlying mechanisms of a link between SAR and affect, however, are still unclear. The objective of the present study was to investigate depressive symptoms and anxiety in SAR patients and their association to inflammatory and endocrine parameters. SAR patients (n=41) and non-allergic, healthy controls (n=42) were assessed during (pollen season) and out of symptomatic periods (non-pollen season). Inflammatory cytokine profile (Interleukin [IL]-2, IL-4, IL-6, IL-8, IL-10, IL-17, IFN-γ, TNF-α), Immunoglobulin-E (IgE), hair cortisol concentrations (HCC), as well as sleep quality were measured. The present data show that during acute allergic inflammation SAR patients experienced a significant increase in Beck Depression Inventory (BDI-) II scores when (a) compared to the asymptomatic period and (b) when compared to the non-allergic controls, while no differences in anxiety were observed. Increased BDI-II scores in SAR patients were significantly associated with levels of IL-6 as well as IL-6/IL-10 and IFN-γ/IL-10 ratios and further, to an early age at manifestation of SAR and poor sleep quality. These findings support a close relationship between acute allergic processes and affective states, with inflammatory cytokines, sleep, and age of manifestation as potentially relevant mediators.

Cancer patients' control preferences in decision making and associations with patient-reported outcomes: a prospective study in an outpatient cancer center.

PURPOSE: "Shared decision making" has been proposed as a prerequisite of patient-centered care. However, little is known on factors, which may influence cancer patients' decision control preferences (DCP) in routine care. This study investigated possible determinants of the patients' DCP with respect to patient characteristics and patient-reported outcomes (PROs). METHODS: Consecutive patients presenting at a comprehensive cancer center between May 2014 and October 2014 were offered a self-administered electronic questionnaire including standardized PRO measures and patients' DCP. Results were linked with patient characteristics from the hospital information system and analyzed using cross-sectional methods. RESULTS: Out of 126 patients participating, 102 (81%; 65% male; mean age 62 years) completed the DCP-item. Overall, 49% (n = 50) preferred shared treatment decision responsibility, 29% (n = 30) preferred to leave the control to his/her physician, whereas 22% (n = 22) preferred to be in control of his/her treatment decision. Higher age (p = 0.035) and elevated distress levels (p = 0.038) were significantly associated with an increased willingness to leave the decision control to the physician. Further sociodemographic and PRO measures were not associated with patients' DCP. CONCLUSION: Our findings demonstrate that DCP assessment in routine cancer care is possible and provides important information to the treating oncologist. Information on DCP combined with PRO may contribute to more individualized decision making in cancer care.

Reliability of specific physical examination tests for the diagnosis of shoulder pathologies: a systematic review and meta-analysis.

BACKGROUND: Shoulder pain in the general population is common and to identify the aetiology of shoulder pain, history, motion and muscle testing, and physical examination tests are usually performed. OBJECTIVE: The aim of this systematic review was to summarise and evaluate intrarater and inter-rater reliability of physical examination tests in the diagnosis of shoulder pathologies. METHODS: A comprehensive systematic literature search was conducted using MEDLINE, EMBASE, Allied and Complementary Medicine Database (AMED) and Physiotherapy Evidence Database (PEDro) through 20 March 2015. Methodological quality was assessed using the Quality Appraisal of Reliability Studies (QAREL) tool by 2 independent reviewers. RESULTS: The search strategy revealed 3259 articles, of which 18 finally met the inclusion criteria. These studies evaluated the reliability of 62 test and test variations used for the specific physical examination tests for the diagnosis of shoulder pathologies. Methodological quality ranged from 2 to 7 positive criteria of the 11 items of the QAREL tool. CONCLUSIONS: This review identified a lack of high-quality studies evaluating inter-rater as well as intrarater reliability of specific physical examination tests for the diagnosis of shoulder pathologies. In addition, reliability measures differed between included studies hindering proper cross-study comparisons. TRIAL REGISTRATION NUMBER: PROSPERO CRD42014009018.

Early comprehensive care of preterm infants-effects on quality of life, childhood development, and healthcare utilization: study protocol for a cohort study linking administrative healthcare data with patient reported primary data.

BACKGROUND: About 9 % of all children in Germany are born preterm. Despite significant improvements of medical care, preterm infants are at a greater risk to develop short and long term health complications. Negative consequences of preterm birth include neurodevelopmental disabilities, behavioral problems or learning disorders. Most data on effects of prematurity are derived from single or multi-center studies and not population-based. Since some of the long term problems of preterm delivery are associated with a disturbed parent-child interaction originating in the neonatal period, several intervention programs became available aiming to strengthen the early parent-child relationship. However, there is insufficient knowledge regarding the psychosocial and socioeconomic impact of these interventions. Prior to introducing them into routine care, those effects have to be rigorously evaluated. The population-based cohort study EcoCare-PIn (Early comprehensive Care of Preterm Infants-effects on quality of life, childhood development, and healthcare utilization) will investigate the following primary research questions: 1) What are the short- and long-term consequences of preterm birth with regard to parental stress, parent-child relationship, childhood development, quality of life and healthcare utilization including costs? 2) Does early family-centered psychosocial care prevent the hypothesized negative consequences of preterm birth on the above mentioned outcomes? METHODS/DESIGN: EcoCare-PIn examines the research questions by means of a linkage of a) pseudonymized administrative individual-level claims data from the German statutory health insurance AOK PLUS on approximately 140,000 children born between 2007 and 2013 in Saxony, and b) primary data collected from the parents/caregivers of all very low birth weight (<1,500 g; n = 1,000) and low birth weight infants (1,500 to 2,500 g; n = 5,500) and a matched sample of infants above 2,500 g birth weight (n = 10,000). DISCUSSION: In Saxony, approximately 50 % of all individuals are insured at the AOK PLUS. The linkage of patient-level administrative and primary data is a novel approach in neonatal research and probably the only way to overcome shortcomings of studies solely relying on one data source. The study results are based on an observation period of up to 8 years and will directly inform perinatal healthcare provision in Saxony and Germany as a whole.

A Questionnaire Study to Assess the Value of the Vulnerable Elders Survey, G8, and Predictors of Toxicity as Screening Tools for Frailty and Toxicity in Geriatric Cancer Patients.

BACKGROUND: The aim of this study was to identify an appropriate screening instrument for the identification of frail elderly patients in a tertiary cancer center. In order to improve cancer care for older patients, the use of a geriatric assessment (GA) has been proposed to identify frail patients or those who are at a higher risk for chemotherapy-related toxicities. In busy clinical routine, an appropriate screening instrument could be used to spare time- and resource-consuming application of GA. PATIENTS AND METHODS: We administered the Vulnerable Elders Survey (VES-13), G8 questionnaire, and Predictors of Toxicity (POT) as well as a GA at the first visit of 84 consecutive patients at a single Comprehensive Cancer Center. Analysis for patients' characteristics as well as sensitivity, specificity, and positive and negative predictive value (npv) was conducted. RESULTS: The median age of the patients was 73 years (range 63-93 years), 61.9% were male, most (63%) suffered from gastrointestinal tumors, 39.3% had a multiple cancer diagnosis, and 53.6% had metastasis. 30 (35.7%) individuals were classified as 'frail' by the GA. Sensitivity of G8 was 38.3%, and the npv was 63.8%. Sensitivity for VES-13 was 57.1%, and npv was 76.3%. Sensitivity of POT was 72.7%, and the npv was 80.6%. CONCLUSION: For the first time, the VES-13, G8, and POT are compared in a sample of older German patients. The POT seems to be a sufficient screening tool to identify frail patients in a tertiary referral cancer center and helps to save time and resources compared with a complete GA.

Electronic real-time assessment of patient-reported outcomes in routine care-first findings and experiences from the implementation in a comprehensive cancer center.

PURPOSE: Cancer patients suffer from a variety of physical and mental complaints. Since physician assessment of symptoms seems insufficient to reveal the complete range of patients' ailments, patient-reported outcomes (PRO) have become of key importance in modern cancer treatment. The implementation and first results of a systematic electronic real-time assessment of PRO in routine care is described. METHODS: Consecutive patients presenting for the first time to a German comprehensive cancer center were asked to fill in an adaptive self-administered electronic questionnaire consisting of standardized PRO measures. After completion, patient-reported data was linked to the patients' medical files for discussion in the first consultation with the treating physician. Interviews with staff were conducted to identify barriers in implementation. RESULTS: Out of 160 cancer patients, 126 (79 %; mean age 63 years, 67 % males) agreed to participate. The number of recruited patients increased over time. Of participating patients, 67 % provided complete information on all PRO-related scales. On average, 31 min (range 3-140) were required to fill in the questionnaire. Of participating patients, 53.0 % comprised need for psychooncological support and 62 % revealed moderate to severe psychosocial distress. The mean score for global quality of life according to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) was 55.2 (SD ±25.6). CONCLUSIONS: Comprehensive oncological treatment needs to consider disease symptoms, quality of life, preferences, and comorbidities of individual patients in a structured, standardized, and transparent way. Our findings indicate that an adaptive, self-administered electronic assessment tool for cancer patients to report a broad set of PRO can be feasibly implemented and is well accepted by patients in a realistic setting.

[Indication for total knee arthroplasty: evidence mapping]. / Indikation zur endoprothetischen Versorgung des Kniegelenks - ein Evidence Mapping.

BACKGROUND: Joint replacement surgery is one of the most often performed routine procedures for the treatment of knee osteoarthritis in Germany. Currently, there is no consensus on indication criteria for total knee arthroplasty (TKA). OBJECTIVES: The topic indication for TKA was processed using six guiding questions concerning: 1) Common practice in determining the indication for TKA; 2) Inclusion criteria in clinical trials; 3) Treatment goals/goal criteria; 4) Predictors for goal attainment; 5) Economic aspects of determining a TKA indication; 6) Guidelines of the "Working Group of Scientific Medical Societies" (AWMF) in other areas. METHODS: The evidence mapping was conducted by systematically searching Medline via Ovid, the Cochrane Library, through hand searching national guidelines and selected journals as well as the AWMF guideline portal. RESULTS OF THE GUIDING QUESTIONS: 1) In Germany there is currently no consented guideline regarding indications for TKA surgery. 2) Indication criteria for clinical trials are: diagnosed osteoarthritis of the knee, limitations of age and BMI. The most common criteria for exclusion include rheumatoid/inflammatory arthritis, secondary diagnoses and allergies. 3) As yet, no international initiatives have been identified which, by involving all relevant stakeholders, have reached consensus regarding the indication criteria for TKA. 4) A variety of predictors were identified with effects on individual treatment goals acting in different directions. 5) Very few studies were identified concerning economic aspects of determining TKA indication. 6) Comparable AWMF guidelines are currently not available. CONCLUSION: The findings of this study suggest that specific systematic reviews are needed to explore the following questions: What are the treatment goals of a TKA intervention? For whom are these relevant? And how are they measured? Continuous analyses are recommended in the field of predictors for a positive TKA outcome.

Efficacy and safety of systemic treatments for moderate-to-severe atopic dermatitis: a systematic review.

BACKGROUND: Many patients with moderate-to-severe atopic dermatitis (AD) require systemic immunomodulating treatment to achieve adequate disease control. OBJECTIVE: We sought to systematically evaluate the efficacy and safety of systemic treatments for moderate-to-severe AD. METHODS: A systematic literature search was performed in MEDLINE, EMBASE, and CENTRAL (until June 2012). Randomized controlled trials (RCTs) evaluating systemic immunomodulating treatments for moderate-to-severe AD were included. Selection, data extraction, quality assessment, and generation of treatment recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach were performed independently by 2 reviewers. Efficacy outcomes were clinical signs, symptoms, quality of life, and the course of AD. Safety data were compared by calculating the weekly incidence rates (as percentages) for adverse events. RESULTS: Thirty-four RCTs with 12 different systemic treatments and totaling 1653 patients were included. Fourteen trials consistently indicate that cyclosporin A efficaciously improves clinical signs of AD. Cyclosporin A is recommended as first-line treatment for short-term use. A second-line treatment option is azathioprine, but efficacy is lower, and evidence is weaker. Methotrexate can be considered a third-line treatment option. Recommendations are impossible for mycophenolate, montelukast, intravenous immunoglobulins, and systemic glucocorticosteroids because of limited evidence. A meta-analysis was not performed because of a lack of standardization in outcome measures. CONCLUSION: Although 12 different interventions for moderate-to-severe AD have been studied in 34 RCTs, strong recommendations are only possible for the short-term use of cyclosporin A. Methodological limitations in the majority of trials prevent evidence-based conclusions. Large head-to-head trials evaluating long-term treatments are required.

Physical examination tests for the diagnosis of posterior cruciate ligament rupture: a systematic review.

STUDY DESIGN: Systematic literature review. OBJECTIVES: To summarize and evaluate research on the accuracy of physical examination tests for diagnosis of posterior cruciate ligament (PCL) tear. BACKGROUND: Rupture of the PCL is a severe knee injury that can lead to delayed rehabilitation, instability, or chronic knee pathologies. To our knowledge, there is currently no systematic review of studies on the diagnostic accuracy of clinical examination tests to evaluate the integrity of the PCL. METHODS: A comprehensive systematic literature search was conducted in MEDLINE from 1946, Embase from 1974, and the Allied and Complementary Medicine Database from 1985 until April 30, 2012. Studies were considered eligible if they compared the results of physical examination tests performed in the context of a PCL physical examination to those of a reference standard (arthroscopy, arthrotomy, magnetic resonance imaging). Methodological quality assessment was performed by 2 independent reviewers using the revised version of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. RESULTS: The search strategy revealed 1307 articles, of which 11 met the inclusion criteria for this review. In these studies, 11 different physical examination tests were identified. Due to differences in study types, different patient populations, and methodological quality, meta-analysis was not indicated. Presently, most physical examination tests have not been evaluated sufficiently enough to be confident in their ability to either confirm or rule out a PCL tear. CONCLUSIONS: The diagnostic accuracy of physical examination tests to assess the integrity of the PCL is largely unknown. There is a strong need for further research in this area. Level of Evidence Diagnosis, level 3a.

Metal ion concentrations in body fluids after implantation of hip replacements with metal-on-metal bearing--systematic review of clinical and epidemiological studies.

INTRODUCTION: The use of metal-on-metal (MoM) total hip arthroplasty (THA) increased in the last decades. A release of metal products (i.e. particles, ions, metallo-organic compounds) in these implants may cause local and/or systemic adverse reactions. Metal ion concentrations in body fluids are surrogate measures of metal exposure. OBJECTIVE: To systematically summarize and critically appraise published studies concerning metal ion concentrations after MoM THA. METHODS: Systematic review of clinical trials (RCTs) and epidemiological studies with assessment of metal ion levels (cobalt, chromium, titanium, nickel, molybdenum) in body fluids after implantation of metalliferous hip replacements. Systematic search in PubMed and Embase in January 2012 supplemented by hand search. Standardized abstraction of pre- and postoperative metal ion concentrations stratified by type of bearing (primary explanatory factor), patient characteristics as well as study quality characteristics (secondary explanatory factors). RESULTS: Overall, 104 studies (11 RCTs, 93 epidemiological studies) totaling 9.957 patients with measurement of metal ions in body fluids were identified and analyzed. Consistently, median metal ion concentrations were persistently elevated after implantation of MoM-bearings in all investigated mediums (whole blood, serum, plasma, erythrocytes, urine) irrespective of patient characteristics and study characteristics. In several studies very high serum cobalt concentrations above 50 µg/L were measured (detection limit typically 0.3 µg/L). Highest metal ion concentrations were observed after treatment with stemmed large-head MoM-implants and hip resurfacing arthroplasty. DISCUSSION: Due to the risk of local and systemic accumulation of metallic products after treatment with MoM-bearing, risk and benefits should be carefully balanced preoperatively. The authors support a proposed "time out" for stemmed large-head MoM-THA and recommend a restricted indication for hip resurfacing arthroplasty. Patients with implanted MoM-bearing should receive regular and standardized monitoring of metal ion concentrations. Further research is indicated especially with regard to potential systemic reactions due to accumulation of metal products.