BACKGROUND AND OBJECTIVES:Multimorbidity, the coexistence of two or more chronic conditions, affects about 40% of all adults and over half of adults over 60 years. The complexity of multimorbidity (MM) often renders traditional trial designs inadequate, unable to account for the context of interventions, including the interplay of multiple health conditions in daily life. This gap reduces the generalizability and applicability of their results. METHODS:This commentary aims to review the current state of trials targeting or involving patients with MM. Highlighting current limitations and drawing on insights from an international dedicated workshop in Bielefeld, Germany, we identify an ongoing and pressing need for innovative, patient-centered approaches to their design and conduct. RESULTS:We propose a shift toward more holistic and integrative experimental approaches, including developing interventions tailored to the characteristics and needs of patients with MM, establishing relevant outcomes, and enhancing data collection and process evaluation. We specifically advocate for adaptive trial designs, prespecified subgroup analyses, and the incorporation of patient-reported outcomes and experience measures such as burden of care to ensure that research is both comprehensive and reflective of the needs of patients living with MM, their caregivers, and of the clinicians participating in their care. Ethical considerations are discussed in our commentary as well, emphasizing the importance of patient safety, data protection, and informed consent. Finally, we call for the development of specific reporting guidance, such as a SPIRIT extension tailored to MM trials, to help researchers adapt standard protocols to the complex and heterogeneous reality of this population. CONCLUSION:This commentary aims to bridge the gap between research and practice, fostering the development of effective interventions that improve patient outcomes and enhance the quality of care for patients living with MM.

Abstract Background The cluster randomized controlled trial interprof ACT evaluated the effects of a complex intervention designed to improve collaboration between general practitioners (GPs) and registered nurses (RNs) in nursing homes (NHs). The intervention includes six components (“Name badges”, “Mandatory availability rules”, “Designated contact persons”, “Standardized GPs’ home visits”, “Pro re nata medication”, “Shared goal setting”). The findings showed a nonsignificant reduction in hospital admissions in the intervention group (IG) compared to the control group (CG) within twelve months. The aims of this process evaluation were to describe (1) the dose, reach and fidelity of implementation (“implementation performance”), (2) the effects on the quality of RN-GP collaboration, and (3) potential moderating factors. Methods Process evaluation with a mixed-methods triangulation design involving all clusters (17 NHs per IG and CG) and 323 nursing home residents (NHRs) (n = 166 IG, n = 157 CG): We collected quantitative and qualitative data from multiple perspectives (e.g., RNs, GPs, NHRs) at several measurement points. We quantitatively compared groups by means of medians, interquartile ranges, proportions (all outcome domains) or Mann‒Whitney U tests (implementation performance) and analyzed qualitative data inductively via content analysis. The key findings were triangulated narratively and via a joint display. Results Compared to those in the CG, we noted relevant improvements in the implementation of “Name badges”, “Mandatory availability rules”, “Designated contact persons” and “Pro re nata medication” in ≥50% of the IG clusters, of which the group difference for “Mandatory availability rules” reached statistical significance. The implementation performance of IG clusters was moderated by resource-related and other organizational attributes of NHs and GP offices and attributes of involved professionals, especially their attitudes and awareness. Implementation of the components induced greater standardization of care processes together with positive changes in interprofessional communication and coordination among GPs and RNs. Conclusions Implementation of the interprof ACT components varied between components and NHs but showed potential for improving RN-GP collaboration. The standardization of shared care procedures emerged as a key mediator for improvement. For larger and more sustainable implementation we recommend a stronger focus on locally available resources and communication of potential benefits for all involved parties. Trial registration ClinicalTrials.gov, NCT03426475; registered 07 February 2018, https://www.clinicaltrials.gov/study/NCT03426475?lead=NCT03426475%26;rank=1 .

In Germany, patients with chronic non-malignant diseases (CNMD) are predominantly treated by general practitioners (GPs). Yet, little is known about communication between GPs and specialist palliative home care (SPHC) teams in terms of care needs and care planning for patients. Our analysis therefore aims at GPs´, SPHC nurses’ and SPHC physician’s interaction during case conferences (CCs) on patients with CNMD following an initial comprehensive palliative care consultation. A total of 78 CCs were conducted between January 2020 and March 2021 by telephone and recorded by non-participating observers using pre-categorized protocol forms. Content, course and patterns of communication of the participating 25 GPs, 16 SPHC nurses and 11 SPHC physicians are investigated by secondary document analysis with methodical reference to Kuckartz’s structuring content analysis. CCs were characterized by a cooperative and welcoming atmosphere, focussing on the patient’s situation. CCs were mainly started and facilitated by the SPHC nurses. Most GPs showed great interest in nurses’ narrations and suggestions for improvement. GPs received important new information about their patients in some CCs. SPHC physicians mainly addressed medication regimens and emergency prevention. CCs’ participants interacted constructively in a positive atmosphere on an equal level. SPHC nurses hold a central role. We conclude that interprofessional CCs might support the improvement of health care of chronically ill patients by common reflection and the development of therapy goals and care plans. Increased structuring of CCs might trigger more specific treatment plans. KOPAL is registered on the German clinical trial register “Deutsches Register Klinischer Studien (DRKS)” (registration number DRKS00017795 17 November 2021, V.05).

Background International guidelines recommend risk-adapted depression screening in primary care. However, empirical evidence on the diagnostic accuracy of depression screening questionnaires in patients at risk for depression remains limited. Objective To evaluate the diagnostic accuracy of the Patient Health Questionnaire-9 (PHQ-9) for detecting major depressive disorder (MDD) in primary care, stratified by the presence of single depression-related risk factors and the amount of risk factors. Methods This secondary analysis used data from 985 primary care patients participating in the GET.FEEDBACK.GP trial who completed the PHQ-9, a depression-related risk factor assessment, and underwent evaluation for MDD using the Mini-International Neuropsychiatric Interview (MINI). Accounting for partial verification bias, this study applied an inverse probability weighting normalized for a sample of 985. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the area under the curve (AUC) were calculated for different PHQ-9 cut-off scores across single risk factors and the amount of risk factors. The analysis was pre-registered (https://osf.io/wzctq). Results Of 985 participants, 89 (9.1%) had a MDD diagnosis. The best-performing PHQ-9 cut-offs, stratified by the amount of risk factors, varied, ranging from 7 to 13, with a higher number of risk factors being associated with a higher best-performing PHQ-9 cut-off score. Sensitivity ranged from 0.78 to 0.99; specificity from 0.80 to 0.91. PPV ranged from 0.40 to 0.88 and NPV from 0.80 to 0.99. AUCs ranged from 0.92 to 0.97, indicating excellent diagnostic accuracy. Similar results were found when stratifying by single risk factors. Conclusions The PHQ-9 demonstrated high diagnostic accuracy for detecting MDD in patients at risk for depression. Although optimal cut-offs vary slightly according to the number and type of risk factors present, the findings support the validity of risk-adapted depression screening using the PHQ-9 in primary care.

INTRODUCTION:We evaluated the prognostic value of baseline plasma phosphorylated tau 217 ratio (%p-tau217) for predicting long-term progression in cognitively unimpaired (CU) older adults. METHODS:We analyzed 982 community-dwelling individuals followed annually for up to 12 years. Baseline %p-tau217 levels were quantified by mass spectrometry and stratified into four strata using previously defined cut-offs. Outcomes included longitudinal changes in cognition, neurodegeneration, and progression to mild cognitive impairment (MCI)/dementia. Results were replicated with immunoassays in the same and an independent primary care cohort (n = 1204). RESULTS:Participants with Elevated/High %p-tau217 exhibited accelerated cognitive decline, hippocampal atrophy, and significantly higher risks of progression to MCI (hazard ratio [HR] > 6.0) and dementia (HR > 9.9). The Low group demonstrated a 92.2% 10-year negative predictive value for any progression. DISCUSSION:Our results suggest that %p-tau217 is a robust prognostic biomarker, accurately distinguishing CU individuals at minimal risk from those at high risk of future AD-related clinical and neurodegenerative decline. Similar performance was achieved by immunoassays.

BACKGROUND:Many patients in intensive care cannot communicate their preferences about treatment, therapeutic goals, and expectations of quality of life, and physicians must therefore speak to their families to determine what they would want. We studied the accordance between patients' preferences about intensive care and the worst impairment of quality of life that they would be willing to accept and their families' assessment of these preferences. METHODS:Inpatients on non-intensive-care wards at risk for future need of intensive care and their relatives were separately asked about the patient's wishes concerning eight treatment options and six quality-of-life goals. Degrees of accordance were studied with simple matching and Manhattan Distance Scores, and associations between patient features and degrees of accordance were determined by linear regression analysis. RESULTS:Actual and presumed patient wishes agreed in 82.1% of cases on average. Depending on the measure in question, 1.0% to 8.6% of families wrongly thought that the patient would reject it, and 0% to 6.7% wrongly thought that the patient would accept it. The postulated and actual wishes of the patient about tolerable impairments of quality of life agreed in 86.4% of cases on average. Degrees of accordance were greater when the family members' wishes for themselves more closely resembled those of the patient (adjusted mean differences: 0.52, 95% confidence interval [0.39; 0.65], p < 0.001 and 0.66 [0.51; 0.81], p < 0.001). CONCLUSION:When patients' wishes are misjudged, the treatment they receive may not be in their best interest. Clear communication ahead of time between patients and their relatives, as well as the provision of information on this topic in advance by medical personnel, may lessen uncertainty about future intensive care.

Patient*innen mit chronischen, nicht-onkologischen Erkrankungen erhalten seltener spezialisierte Palliativversorgung (SAPV) als jene mit onkologischen Erkrankungen. Die KOPAL-Studie untersuchte die Durchführung einer zeitgerechten Fallbesprechung durch SAPV-Pflegefachpersonen (SAPV-PP), Palliativmediziner*in und Hausärzt*in. Ziel ist die Bewertung der Intervention aus SAPV-PP-Sicht. 16 thematisch fokussierte, narrative Interviews mit SAPV-PPs, Analyse mittels Grounded Theory. Im Falle einer SAPV-Zuweisung der Patient*innen sollte diese zeitgerecht und gemeinsam mit Hausärzt*innen erfolgen. Die Zusammenarbeit mit Hausärzt*innen erleben die SAPV-PPs als Balanceakt. Zudem fühlen sie sich durch die Intervention in ihrem Vorgehen im Patient*innengespräch eingeschränkt. Sie nehmen ihre gewohnte, beratende Rolle ein und erleben es als Belastung, wenn keine gemeinsame Versorgung erfolgt. Eine Zusammenarbeit von Hausärzt*innen und SAPV-PPs sollte frühzeitig unter besonderer Beachtung der Pflegeperspektive umgesetzt werden.

OBJECTIVE:One of the conclusions from the experience with the SARS-CoV-2 pandemic of 2020 to 2022 was the requirement for data on primary care/ambulatory care to assess the severity of the pandemic in a timely manner. Since most patients with COVID-19 in Germany had been primarily cared for by general practitioners, the question arose whether the incidence course of a pandemic can be mapped by means of a regular evaluation of GP workload and number of patients. METHODS:From January 2021 to June 2021, 12 replicative, internet-based cross-sectional surveys were conducted fortnightly. Invitations were sent out to all members of the German Society of General Practice/Family Medicine (DEGAM) and selected federal/regional member organizations of the German Association of General Practitioners. They were asked about increases in personal workload, number of patients with COVID-19, and other conditions of patient care. RESULTS:On average, 697 general practitioners (GPs) participated in each survey and completed a total of 8,369 questionnaires. The composition of participants remained consistent across the 12 survey periods, with 82.9-87.2 % being practice owners and 32.0-40.7 % working in group practices. Over time, the proportion of physicians reporting an increased workload reached a minimum of 24.2 % in February 2021; from March 2021 onward, there was a trend reversal with a peak (88.1 %) in May 2021. The change in the GPs' workload developed in phases that ran parallel to the official RKI reporting data on the COVID-19 incidence. The reported increase in the care deficit for patients with chronic diseases or social problems did not show a temporal dynamic comparable to the reported incidence trend. DISCUSSION:A replicative survey among GPs conducted between January 2021 and June 2021 revealed changes in the workload of general practitioners under pandemic conditions. The progression of the SARS-CoV-2 pandemic during the same period and the observed change in workload developed in parallel. The methodology used (an internet-based, replicative survey among GPs) could therefore be a low-threshold, resource-saving approach to assessing the course of a pandemic. Despite the increasing workload during the different waves of the pandemic, the care for chronically ill patients reported by the GPs was not subject to any pandemic-related dynamics.

In order to reduce the health burden and the health care costs caused by the most common mental disorders, health care systems throughout Europe have tried to improve services and treatment choices. Recently, a collaborative and stepped care (CSC) model for patients with depressive, anxiety, somatoform or alcohol-related disorders and their comorbidities was developed and implemented under routine care conditions in Germany. The aim of this study was to determine the cost-effectiveness of this CSC model from a societal perspective with a 12-month follow-up. This study was part of a cluster-randomized controlled trial to compare a CSC model with treatment as usual (TAU) in patients with depressive, anxiety, somatoform or alcohol-related disorders and their comorbidities in German routine care. The cost-effectiveness of the CSC model compared with TAU was analyzed based on the incremental cost-utility ratio (ICUR) with quality-adjusted life years (QALYs) based on the EQ-5D-5L index as measure of health effect. The uncertainty of the ICUR was assessed using cost-effectiveness acceptability curves based on net-benefit regressions. In total, n = 307 patients in the CSC and n = 308 patients in the TAU group were included, with a mean age of 38 and 43 years, respectively. There were no differences in mean QALYs and total costs between the CSC (0.86 QALY, 27,174€) and the TAU group (0.86 QALY, 26,441€). Only the adjusted mean costs for outpatient mental health services were higher in the CSC group (+685€; 95

BACKGROUND:Collaborative and stepped care (CSC) models are recommended in guidelines because of their effectiveness in treating depression and anxiety disorders. The evidence for other mental disorders is, however, limited. The aim of this study was to evaluate the effectiveness of a collaborative and stepped care model (COMET) for patients with depressive, anxiety, somatoform, and/or alcohol-related disorders and related comorbidities in the routine care setting in Germany. METHODS:A prospective, cluster-randomized, controlled, parallelgroup superiority trial was conducted; the subjects were patients in primary care practices. The primary endpoint was the change in mental health-related quality of life, assessed with the SF-36 Mental Health Component Summary Score (MCS) at 6 months in the intention-to-treat population. The secondary endpoints were symptom severity, remission, and response. RESULTS:Forty-one primary care offices were randomized either to COMET (n = 20) or treatment as usual (TAU, n = 21), and 615 patients were recruited (CSC: n = 307; TAU: n = 308). Data were available for 62% (COMET) and 55% (TAU) of the participants at 6 months. No significant group difference was found with respect to the primary endpoint (-1.96 ,95% confidence interval [-4.39; 0.48], p = 0.113) or any of the secondary endpoints. CONCLUSION:We found no superiority of the COMET model for the mental disorders addressed. Methodological issues, including differences at baseline and high dropout rates, make these findings challenging to interpret. Future studies should ensure comparability of groups, allocate resources for quality management, and investigate more suitable outcome measures, paying attention to factors of implementation.

Neuropsychiatric symptoms are common in Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD), yet their genetic underpinnings remain unclear. To gain insight into biological processes related to neuropsychiatric symptoms in dementia, we investigated whether polygenic risk scores (PRS) for psychiatric disorders - major depressive disorder (MDD), schizophrenia (SCZ), bipolar disorder (BD), and autism spectrum disorder (ASD) - are associated with neuropsychiatric symptoms in dementia. Data included genetic and neuropsychiatric data of 6240 AD patients, 428 FTD patients and 390 DLB patients from five European cohorts (ADC, GR@ACE, DELCODE, AgeCoDe, and DCN). PRS for MDD, BD, SCZ, and ASD were calculated using LDpred2. Neuropsychiatric symptoms were assessed using total scores from the Neuropsychiatric Inventory (NPI) (NPI-12 and NPI-Q) and Geriatric Depression scale (GDS). Associations between PRS and symptoms were examined using linear regression models, followed by meta-analyses. In FTD, higher SCZ-PRS associated with lower NPI scores in the meta-analysis (β = -0.12, p = .001). No associations were found in AD and DLB. This is the first study to show that genetic liability for SCZ associates with lower NPI in FTD, warranting further investigation.

Objective Patients with progressive chronic non-malignant diseases (CNMD) such as chronic obstructive pulmonary disease, congestive heart failure and dementia could benefit from specialist palliative home care (SPHC). The two-arm, cluster randomised controlled KOPAL trial was conducted to test the effectiveness of a timely SPHC nurse-patient consultation followed by an interprofessional telephone case conference between general practitioners and SPHC teams. This study was a component of the KOPAL trial and aims to explore general practitioners’ (GP) experiences with treating CNMD patients before and with case conferences and with the following consequences for treatment and interprofessional collaboration with SPHC teams.Design Qualitative evaluation of the KOPAL trial focussing on GPs’ perspective. Open guided interviews using narrative techniques analysed with grounded theory.Setting The KOPAL trial was conducted in Lower Saxony and the metropolitan region of Hamburg, Germany.Participants 24 GPs who participated in the intervention group of the trial were interviewed.Results Findings show that GPs have practice-specific routines when caring for people with CNMD. Interprofessional case conferences may lead to more awareness regarding gaps in primary palliative care, one’s own care routines or a lack of psychosocial support. Although gaining new insights, GPs follow three different strategies following the case conferences: (1) Maintain routines of care and disregard added value, (2) extend routines of care according to SPHC advice and (3) integration and partial change of care routines caused by SPHC support. These strategies are influenced by GPs’ perception of SPHC teams (eg, ambivalence towards SPHC).Conclusion Interprofessional case conferences to timely discuss care options could improve healthcare for patients with advanced CNMD by revealing gaps in care. Promoting a regular process of exchange between GPs and SPHC teams (such as through round tables) may improve a trusting cooperation.Trial registration number DRKSS00017795.