[Benefit assessment of diagnostics - Dealing with incomplete evidence]. / Nutzenbewertung von Diagnostik ­ Umgang mit unvollständiger Evidenz.

Incomplete evidence in diagnostic studies results from missing or too few randomised test-treatment studies or from studies of too low quality. In order to be able to carry out a benefit assessment, it is helpful in the first step to design a hypothetical randomised test-treatment study. In the second step, the linked evidence approach can be used to link the evidence of the individual components of the test-treatment pathway and to assess the potential benefits and risks. In the third step, based on the linked evidence approach, decision analytic models can be used to quantify the benefit-risk ratio. In the case of incomplete evidence, the assessment can thus be made by linking the individual components of the test-treatment pathway, provided that their evidence is sufficient.

Effectiveness of a complex regional advance care planning intervention to improve care consistency with care preferences: study protocol for a multi-center, cluster-randomized controlled trial focusing on nursing home residents (BEVOR trial).

BACKGROUND: According to recent legislation, facilitated advance care planning (ACP) for nursing home (NH) residents is covered by German sickness funds. However, the effects of ACP on patient-relevant outcomes have not been studied in Germany yet. This study investigates whether implementing a complex regional ACP intervention improves care consistency with care preferences in NH residents. METHODS: This is a parallel-group cluster-randomized controlled trial (cRCT) with 48 NHs (≈ 3840 resident beds) between 09/2019 and 02/2023. The intervention group will receive a complex, regional ACP intervention aiming at sustainable systems redesign at all levels (individual, institutional, regional). The intervention comprises comprehensive training of ACP facilitators, implementation of reliable ACP processes, organizational development in the NH and other relevant institutions of the regional healthcare system, and education of health professionals caring for the residents. Control group NHs will deliver care as usual. Primary outcome is the hospitalization rate during the 12-months observation period. Secondary outcomes include the rate of residents whose preferences were known and honored in potentially life-threatening events, hospital days, index treatments like resuscitation and artificial ventilation, advance directives, quality of life, psychological burden on bereaved families, and costs of care. The NHs will provide anonymous, aggregated data of all their residents on the primary outcome and several secondary outcomes (data collection 1). For residents who have given informed consent, we will evaluate care consistency with care preferences and further secondary outcomes, based on chart reviews and short interviews with residents, surrogates, and carers (data collection 2). Process evaluation will aim to explain barriers and facilitators, economic evaluation the cost implications. DISCUSSION: This study has the potential for high-quality evidence on the effects of a complex regional ACP intervention on NH residents, their families and surrogates, NH staff, and health care utilization in Germany. It is the first cRCT investigating a comprehensive regional ACP intervention that aims at improving patient-relevant clinical outcomes, addressing and educating multiple institutions and health care providers, besides qualification of ACP facilitators. Thereby, it can generate evidence on the potential of ACP to effectively promote patient-centered care in the vulnerable population of frail and often chronically ill elderly. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT04333303 . Registered 30 March 2020.

A Care Concept of Community Health Nursing Interventions for Adults With Chronic Health Conditions in an Urban Area: Protocol for a Randomized Controlled Field Trial (CoSta Study).

BACKGROUND: Implementing community health nursing programs is a new field of application in the primary health sector of Germany. Hence, there is limited evidence of effective community-based and nurse-led interventions with regard to the German health care system. International research findings are mostly not transferable. The Community Health Nursing in der Stadt (CoSta; ie, "Community Health Nursing in the City") project is the first study that examines a community health nurse-led intervention for adults with chronic health conditions. OBJECTIVE: This study protocol describes the design and methods of a randomized controlled field trial that will investigate if a community health nurse-based intervention has an impact on health-related quality of life in adults with chronic conditions. METHODS: The study was designed as a randomized controlled trial that will be conducted under real-life conditions in the field. In a 4-month period, patients with at least 1 chronic International Classification of Diseases, Tenth Revision, diagnosis will be enrolled. Participants will be randomly allocated to an intervention group or a control group. The sample size was assumed based on an effect size of 0.50 with a significance level of .05, using a 2-sided (2-tailed), 2-sample unequal variance t test. The control group will be treated as usual. The intervention group will receive-in addition to the usual treatment-preventive home visits; consultations; and educative training, which will be offered by 2 community health nurses for up to 12 months. Both groups will be followed up at baseline, after 6 months, and after 12 months. The primary outcome measure is the mental component summary score from the 36-Item Short Form Health Survey after 12-months. Secondary patient outcomes will be included. The study received ethics approval from the Competence Health Center's institutional review board at the University of Applied Sciences Hamburg (procedure number: 2020-14). RESULTS: The CoSta project was funded by the Federal Ministry of Education and Research Germany (contract number: 13FH019SX8). In total, 187 participants were recruited at the beginning of August 2021. Further, 92 were excluded and 94 were randomized. Data collection will be conducted until the end of 2022. CONCLUSIONS: Our study will provide data with regard to the effectiveness of community nurse-led interventions that focus on the treatment of vulnerable adults with chronic health conditions in a community health center. In secondary analyses, the associations among influencing social factors (education, income, and employment) will be examined. We expect results that will help reduce the research-to-practice gap. TRIAL REGISTRATION: German Clinical Trials Register DRKS00026164; https://tinyurl.com/yckxc5ut. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37965.

Interdisciplinary, internet-based trans health care (i²TransHealth): study protocol for a randomised controlled trial.

INTRODUCTION: Living in an area with no or deficient structures for trans health care is disadvantageous for trans people. By providing an internet-based health care programme, i²TransHealth aims at reducing structural disadvantages for trans people living in areas lacking specialised care. The e-health intervention consists of video consultations and a 1:1 chat with a study therapist. Additionally, the i²TransHealth network cooperates with physicians, who especially offer crisis intervention close to the participants' place of residence. The aim of this study is to evaluate the (cost-)effectiveness of the internet-based health care programme for trans people compared with a control (waiting) group. The following research questions will be examined with a sample of 163 trans people: Does a 4-month treatment with the i²TransHealth internet-based health care programme improve patient-reported health-outcomes? Is i²TransHealth cost-effective compared with standard care from a societal or health care payers' perspective? Does the participation in and support by i²TransHealth lead to an increase of trans-related expertise in the physician network? METHODS AND ANALYSIS: In a randomised controlled trial, the outcomes of an internet-based health care programme for trans people will be investigated. In the intervention group, participants are invited to use i²TransHealth for 4 months. Participants allocated to the control group will be able to start with their transition-related care after 4 months of study participation. The primary outcome measure is defined as the reduction of psychosomatic symptoms, as assessed by the Brief Symptom Inventory-18, 4 months after using the i²TransHealth programme. Participants in both groups will undergo an assessment at baseline and 4 months after using i²TransHealth. ETHICS AND DISSEMINATION: Positive ethical approval was obtained from the Hamburg Medical Association (PV7131). The results will be disseminated to service users and their families via media, to health care professionals via professional training and meetings and to researchers via conferences and publications. TRIAL REGISTRATION NUMBER: NCT04290286. PROTOCOL VERSION: 22 December 2021 (V.1.0).

The efficacy of automated feedback after internet-based depression screening: Study protocol of the German, three-armed, randomised controlled trial DISCOVER.

BACKGROUND: Depression is one of the most disabling disorders worldwide, yet it often remains undetected. One promising approach to address both early detection and disease burden is depression screening followed by direct feedback to patients. Evidence suggests that individuals often seek information regarding mental health on the internet. Thus, internet-based screening with automated feedback has great potential to address individuals with undetected depression. OBJECTIVES: To determine whether automated feedback after internet-based depression screening reduces depression severity as compared to no feedback. METHODS: The internet-based, observer-blinded DISCOVER RCT aims to recruit a total of 1074 individuals. Participants will be screened for depression using the Patient Health Questionnaire (PHQ-9). In case of a positive screening result (PHQ-9 ≥ 10), participants with undetected depression will be randomised into one of three balanced study arms to receive either (a) no feedback (control arm), (b) standard feedback, or (c) tailored feedback on their screening result. The tailored feedback version will be adapted to participants' characteristics, i.e. symptom profile, preferences, and demographic characteristics. The primary hypothesis is that feedback reduces depression severity six months after screening compared to no feedback. The secondary hypothesis is that tailored feedback is more efficacious compared to standard feedback. Further outcomes are depression care, help-seeking behaviour, health-related quality of life, anxiety, somatic symptom severity, intervention acceptance, illness beliefs, adverse events, and a health economic evaluation. Follow-ups will be conducted one month and six months after screening by self-report questionnaires and clinical interviews. According to a statistical analysis plan, the primary outcome will be analysed on an intention-to-treat basis applying multilevel modelling. DISCUSSION: The results of the DISCOVER RCT will inform about how automated feedback after internet-based screening could improve early detection and resolution of depression. Ways of dissemination and how the trial can contribute to an understanding of help-seeking behaviour processes will be discussed. If the results show that automated feedback after internet-based depression screening can reduce depression severity, the intervention could be easily implemented and might substantially reduce the disease burden of individuals with undetected depression. ETHICAL APPROVAL: The study is approved by the Ethics Committee of the Hamburg Medical Association. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov in November 2020 (identifier: NCT04633096).

Biomarker-Guided Risk Assessment for Acute Kidney Injury: Time for Clinical Implementation?

Acute kidney injury (AKI) is a common and serious complication in hospitalized patients, which continues to pose a clinical challenge for treating physicians. The most recent Kidney Disease Improving Global Outcomes practice guidelines for AKI have restated the importance of earliest possible detection of AKI and adjusting treatment accordingly. Since the emergence of initial studies examining the use of neutrophil gelatinase-associated lipocalin (NGAL) and cycle arrest biomarkers, tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein (IGFBP7), for early diagnosis of AKI, a vast number of studies have investigated the accuracy and additional clinical benefits of these biomarkers. As proposed by the Acute Dialysis Quality Initiative, new AKI diagnostic criteria should equally utilize glomerular function and tubular injury markers for AKI diagnosis. In addition to refining our capabilities in kidney risk prediction with kidney injury biomarkers, structural disorder phenotypes referred to as "preclinical-" and "subclinical AKI" have been described and are increasingly recognized. Additionally, positive biomarker test findings were found to provide prognostic information regardless of an acute decline in renal function (positive serum creatinine criteria). We summarize and discuss the recent findings focusing on two of the most promising and clinically available kidney injury biomarkers, NGAL and cell cycle arrest markers, in the context of AKI phenotypes. Finally, we draw conclusions regarding the clinical implications for kidney risk prediction.

Evaluation of two family-based intervention programs for children affected by rare disease and their families - research network (CARE-FAM-NET): study protocol for a rater-blinded, randomized, controlled, multicenter trial in a 2x2 factorial design.

BACKGROUND: Families of children with rare diseases (i.e., not more than 5 out of 10,000 people are affected) are often highly burdened with fears, insecurities and concerns regarding the affected child and its siblings. Although families caring for children with rare diseases are known to be at risk for mental disorders, the evaluation of special programs under high methodological standards has not been conducted so far. Moreover, the implementation of interventions for this group into regular care has not yet been accomplished in Germany. The efficacy and cost-effectiveness of a family-based intervention will be assessed. METHODS/DESIGN: The study is a 2x2 factorial randomized controlled multicenter trial conducted at 17 study centers throughout Germany. Participants are families with children and adolescents affected by a rare disease aged 0 to 21 years. Families in the face-to-face intervention CARE-FAM, online intervention WEP-CARE or the combination of both will be treated over a period of roughly 6 months. Topics discussed in the interventions include coping, family relations, and social support. Families in the control condition will receive treatment as usual. The primary efficacy outcome is parental mental health, measured by the Structured Clinical Interview for DSM-IV (SCID-I) by blinded external raters. Further outcomes will be assessed from the parents' as well as the children's perspective. Participants are investigated at baseline, 6, 12 and 18 months after randomization. In addition to the assessment of various psychosocial outcomes, a comprehensive health-economic evaluation will be performed. DISCUSSION: This paper describes the implementation and evaluation of two family-based intervention programs for Children Affected by Rare Disease and their Family's Network (CARE-FAM-NET) in German standard care. A methodologically challenging study design is used to reflect the complexity of the actual medical care situation. This trial could be an important contribution to the improvement of care for this highly burdened group. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00015859 (registered 18 December 2018) and ClinicalTrials.gov : NCT04339465 (registered 8 April 2020). Protocol Version: 15 August 2020 (Version 6.1). Trial status: Recruitment started on 1 January 2019 and will be completed on 31 March 2021.

Economic impact of heart failure with preserved ejection fraction: insights from the ALDO-DHF trial.

AIMS: Although heart failure (HF) with preserved ejection fraction (HFpEF) is a leading cause for hospitalization, its overall costs remain unclear. Therefore, we assessed the health care-related costs of ambulatory HFpEF patients and the effect of spironolactone. METHODS AND RESULTS: The aldosterone receptor blockade in diastolic HF trial is a multicentre, prospective, randomized, double-blind, placebo-controlled trial conducted between March 2007 and April 2011 at 10 sites in Germany and Austria that included 422 ambulatory patients [mean age: 67 years (standard deviation: 8); 52% women]. All subjects suffered from chronic New York Heart Association (NYHA) class II or III HF and preserved left ventricular ejection fraction of 50% or greater. They also showed evidence of diastolic dysfunction. Patients were randomly assigned to receive 25 mg of spironolactone once daily (n = 213) or matching placebo (n = 209) with 12 months of follow-up. We used a single-patient approach to explore the resulting general cost structure and included medication, number of general practitioner and cardiologist visits, and hospitalization in both acute and rehabilitative care facilities. The average annual costs per patient in this cohort came up to €1, 118 (±2,475), and the median costs were €332. We confirmed that the main cost factor was hospitalization and spironolactone did not affect the overall costs. We identified higher HF functional class (NYHA), male patients with low haemoglobin level, with high oxygen uptake (VO2 max) and coronary artery disease, hyperlipidaemia, and atrial fibrillation as independent predictors for higher costs. CONCLUSIONS: In this relatively young, oligosymptomatic, and with regard to the protocol without major comorbidities patient cohort, the overall costs are lower than expected compared with the HFrEF population. Further investigation is needed to investigate the impact of, for example, comorbidities and their effect over a longer period of time. Simultaneously, this analysis suggests that prevention of comorbidities are necessary to reduce costs in the health care system.