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Purpose This article reports the development of the NOMAD intervention, a model of multidisciplinary team conferences designed to improve care coordination and treatment for patients with multimorbidity and diabetes. Managing multiple chronic conditions increases care complexity, and multidisciplinary approaches may enhance care coherence, optimise treatment, and improve quality of life. Method Guided by the Medical Research Council framework for developing complex interventions, we established a working group, formulated a programme theory, and conducted a preliminary test with qualitative interviews of patients and physicians. The intervention targets patients with diabetes and concurrent chronic conditions affecting the heart, lungs, or kidneys. Results The NOMAD intervention was developed as a structured model of regular, in-person multidisciplinary team conferences involving specialists in endocrinology, cardiology, respiratory medicine, nephrology, and pharmacology. A key component was the integration of patient-reported outcomes to enhance patient-centred care, highlighting the aspect of quality of life. Conclusion This development process provides a foundation for feasibility testing and future evaluation of NOMAD’s impact in a randomised trial. Our experiences may also inform researchers and healthcare providers developing similar multidisciplinary interventions for complex patient populations.

Introduction Multidisciplinary Team Conferences (MDTs) are complex interventions in the modern healthcare system and they promote a model of coordinated patient care and management. However, MDTs within chronic diseases are poorly defined. Therefore, the aim of this scoping review was to summarise the current literature on physician-led in-hospital MDTs in chronic non-malignant diseases. Method Following the PRISMA-ScR guideline for scoping reviews, a search on MDT interventions in adult patients, with three or more medical specialties represented, was performed. Results We identified 2790 studies, from which 8 studies were included. The majority of studies were non-randomised and focused on a single disease entity such as infective endocarditis, atrial fibrillation, IgG4-related disease, or arterial and venous thrombosis. The main reason for referral was confirmation or establishment of a diagnosis, and the MDT members were primarily from medical specialties gathered especially for the MDT. Outcomes of the included studies were grouped into process indicators and outcome indicators. Process indicators included changes in diagnostic confirmation as well as therapeutic strategy and management. All studies reporting process indicators demonstrated significant changes before and after the MDT. Conclusion MDTs within chronic diseases appeared highly heterogeneous with respect to structure, reasons for referral, and choice of outcomes. While process indicators, such as change in diagnosis, and treatment management/plan seem improved, such have not been demonstrated through outcome indicators.

Background The prevalence of diabetes and coexisting multimorbidity rises worldwide. Treatment of this patient group can be complex. Providing an evidence-based, coherent, and patient-centred treatment of patients with multimorbidity poses a challenge in healthcare systems, which are typically designed to deliver disease-specific care. We propose an intervention comprising multidisciplinary team conferences (MDTs) to address this issue. The MDT consists of medical specialists in five different specialities meeting to discuss multimorbid diabetes patients. This protocol describes a feasibility test of MDTs designed to coordinate care and improve quality of life for people with diabetes and multimorbidity. Methods A mixed-methods one-arm feasibility test of the MDT. Feasibility will be assessed through prospectively collected data. We will explore patient perspectives through patient-reported outcomes (PROs) and assess the feasibility of electronic questionnaires. Feasibility outcomes are recruitment, PRO completion, technical difficulties, impact of MDT, and doctor preparation time. During 17 months, up to 112 participants will be recruited. We will report results narratively and by the use of descriptive statistics. The collected data will form the basis for a future large-scale randomised trial. Discussion A multidisciplinary approach focusing on better management of diabetic patients suffering from multimorbidity may improve functional status, quality of life, and health outcomes. Multimorbidity and diabetes are highly prevalent in our healthcare system, but we lack a solid evidence-based approach to patient-centred care for these patients. This study represents the initial steps towards building such evidence. The concept can be efficiency tested in a randomised setting, if found feasible to intervention providers and receivers. If not, we will have gained experience on how to manage diabetes and multimorbidity as well as organisational aspects, which together may generate hypotheses for research on how to handle multimorbidity in the future. Administrative information Protocol version: 01 Trial registration NCT05913726 — registration date: 21 June 2023

Accurate cardiovascular risk estimation in dialysis patients remains challenging because different pathogenetic mechanisms act simultaneously in this heterogeneous population. Radiographic calcification, aortic stiffness and wave reflection, have each individually been proven to be reliable surrogate markers for outcome. We aimed to explore to what extent these parameters intermutually provide complementary or overlapping information. Abdominal aortic calcification scoring of a plain lateral abdominal X-ray, carotid-femoral pulse wave velocity (PWV), and central augmentation index (AIx) were measured in 1084 dialysis patients, recruited from 47 European dialysis centers. Abdominal calcification correlated well with PWV ( R = 0.44, P < 0.001) but poorly with AIx ( R = 0.07, P = 0.04). Next to abdominal calcification, tertiles of PWV were associated with a stepwise increase age, blood pressure, and cardiovascular history, and tertiles of AIx with age, heart rate, and anthropometric factors. In multivariate analysis, only PWV remained significantly associated with calcification score. In addition to age and blood pressure, stiffness was mainly related to diabetes and calcification score ( R 2 = 0.39, P < 0.001), whereas AIx was more dependent on anthropometry, gender and heart rate ( R 2 = 0.36, P < 0.001). Information on aortic calcification and arterial abnormalities can be obtained by simple and inexpensive methodologies. Variation in wave reflections was mainly explained by anthropometric parameters. Stiffness and calcification partly provided complementary information, particularly in low-risk patients. In this group, likely to benefit most from preventive strategies and commonly considered for renal transplantation, evaluation of cardiovascular risk could be made more accurate by the assessment of both aortic calcification and arterial stiffness.

The aim of this preclinical study was to evaluate the characteristics of the monoclonal antibody Rebmab200, which is a humanized version of the ovarian-specific murine antibody MX35. This investigation contributes to the foundation for future clinical α-radioimmunotherapy of minimal residual ovarian cancer with 211At-Rebmab200. Here, the biodistribution of 211At-Rebmab200 was evaluated, as was the utility of 99mTc-Rebmab200 for bioimaging. Rebmab200 was directly compared with its murine counterpart MX35 in terms of its in-vitro capacity for binding the immobilized NaPi2B epitope and live cells; we also assessed its biodistribution in nude mice carrying subcutaneous OVCAR-3 tumors. Tumor antigen and cell binding were similar between Rebmab200 and murine MX35, as was biodistribution, including normal tissue uptake and in-vivo tumor binding. We also demonstrated that 99mTc-Rebmab200 can be used for single-photon emission computed tomography of subcutaneous ovarian carcinomas in tumor-bearing mice. Taken together, our data support the further development of Rebmab200 for radioimmunotherapy and diagnostics.

Objective We aimed to better clarify the role of germline variants of the FCG2 receptor, FCGR2A-H131R and FCGR3A-V158F, on the therapeutic efficacy of cetuximab in metastatic colorectal cancer (mCRC). A large cohort with sufficient statistical power was assembled. Design To show a HR advantage of 0.6 in progression-free survival (PFS) for FCGR2A-HH versus the rest and FCGR3A-VV versus the rest, with an 80% power, 80 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) wild-type (KRAS-WT) and 52 KRAS-WT patients are required, respectively. This leads to a total sample size of 952 and 619 patients, respectively. Samples were collected from 1123 mCRC patients from 15 European centres treated with cetuximab alone or in combination with chemotherapy. Fc gamma receptor (FCGR) status was centrally genotyped. Two additional externally genotyped series were included. Results Incidences of FCGR2A-HH and FCGR3A-VV in KRAS-WT patients were 220/660 (33%) and 109/676 (16.1%) respectively. There was no difference in median PFS (mPFS) for KRAS-WT patients with FCGR2A-HH (22.0 weeks; 95% CI18.8 to 25.2) versus non-HH (22.0 weeks; 95% CI 19.4 to 24.6) or for FCGR3A-VV (16.4 weeks; 95% CI 13.0 to 19.8) versus non-VV (23 weeks; 95% CI 21.1 to 24.9) (p=0.06). Median overall survival, response rate and disease control rate assessments showed no benefit for either HH or VV. Conclusions No differences in mPFS were found between the FCGR polymorphisms HH and the others and VV versus the others in KRAS-WT mCRC patients refractory to irinotecan, oxaliplatin and 5-fluorouracil treated with cetuximab. We cannot confirm the effects of other IgG1 antibodies, which may be weaker than previously suggested. Other markers may be needed to study the actual host antibody response to cetuximab.

Introduction Natalizumab has proved to be more effective than fingolimod in reducing disease activity in relapsing-remitting multiple sclerosis (RRMS). Whether this association is universal for all patient groups remains to be determined. Objective The aim of this study was to compare the relative effectiveness of natalizumab and fingolimod in RRMS subgroups defined by the baseline demographic and clinical characteristics of interest. Methods Patients with RRMS who were given natalizumab or fingolimod were identified in a merged cohort from three international registries. Efficacy outcomes were compared across subgroups based on patients’ sex, age, disease duration, Expanded Disability Status Scale (EDSS) score, and disease and magnetic resonance imaging (MRI) activity 12 months prior to treatment initiation. Study endpoints were number of relapses (analyzed with weighted negative binomial generalized linear model) and 6-month confirmed disability worsening and improvement events (weighted Cox proportional hazards model), recorded during study therapy. Each patient was weighted using inverse probability of treatment weighting based on propensity score. Results A total of 5148 patients (natalizumab 1989; fingolimod 3159) were included, with a mean ± standard deviation age at baseline of 38 ± 10 years, and the majority (72%) were women. The median on-treatment follow-up was 25 (quartiles 15–41) months. Natalizumab was associated with fewer relapses than fingolimod (incidence rate ratio [IRR]; 95% confidence interval [CI]) in women (0.76; 0.65–0.88); in those aged ≤ 38 years (0.64; 0.54–0.76); in those with disease duration ≤ 7 years (0.63; 0.53–0.76); in those with EDSS score < 4 (0.75; 0.64–0.88), < 6 (0.80; 0.70–0.91), and ≥ 6 (0.52; 0.31–0.86); and in patients with pre-baseline relapses (0.74; 0.64–0.86). A higher probability of confirmed disability improvement on natalizumab versus fingolimod (hazard ratio [HR]; 95% CI) was observed among women (1.36; 1.10–1.66); those aged > 38 years (1.34; 1.04–1.73); those with disease duration > 7 years (1.33; 1.01–1.74); those with EDSS score < 6 (1.21; 1.01–1.46) and ≥ 6 (1.93; 1.11–3.34); and patients with no new MRI lesion (1.73; 1.19–2.51). Conclusions Overall, in women, younger patients, those with shorter disease durations, and patients with pre-treatment relapses, natalizumab was associated with a lower frequency of multiple sclerosis relapses than fingolimod. It was also associated with an increased chance of recovery from disability among most patients, particularly women and those with no recent MRI activity.