Multimorbidity contributes significantly to poor population health outcomes while straining healthcare systems. Although some multimorbid patients experience an accelerated health decline (a decline in well-being or functional status that cannot be attributed to the natural ageing-related health deterioration), others can remain stable for years. Identifying risk factors for accelerated health decline in persons with multimorbidity could help prevent complications and reduce unnecessary interventions. Our review, therefore, aims to map the evidence on the clinical, biographical and healthcare-related factors associated with an accelerated health decline in multimorbid individuals.

We will use the evidence-mapping review methodology. We will perform a systematic comprehensive literature search in Medline via Pubmed, Cochrane Library, EMBASE, Web of Science and Google Scholar using two broad concepts: ‘multimorbidity’ and ‘longitudinal studies’. We will search with MeSH terms (eg, ‘Multimorbidity’ (Majr), ‘Longitudinal Studies’ (Majr)) and free text words (eg, multimorbidity, multiple chronic condition*, longitudinal), from inception to date of the final search. All original quantitative studies involving participants in primary care and related healthcare settings will be included. Abstract/titles and full-text screening and data extraction will be performed independently by two or more researchers to minimise selection and reporting bias, with conflicts resolved by consensus. The data will be analysed qualitatively, and topics will be extracted to create evidence clusters. Risk factors will be classified in groups and cross-referenced against the outcomes from respective studies into combinations of exposure-outcome clusters. The resulting evidence clusters will be described narratively and presented as bubble plots. The search, initiated in January 2023, will be updated following this protocol review to reflect the most current evidence; exact dates will be reported in the results manuscript.

Due to the nature of the proposed evidence map, ethics approval will not be required. Results from our research will be disseminated through publications in peer-reviewed journals and presentations at local, national and international conferences.

https://osf.io/q72xa/

‘Hotspotters’ are patients with complex care needs, defined by problems in multiple life domains and high acute care use. These patients often receive mismatched care, resulting in overuse of care and increased healthcare costs. As reliable data on effective interventions for this population are scarce, the goal of this study is to assess the cost-effectiveness of proactive, personalised, integrated care for this group.

The Hotspotters Project is planned as a stepped wedge cluster randomised controlled trial in 20 primary care practices in the Netherlands. All practices and participants will begin with standard care during the control period (2–8 months), followed by an intervention (12 months) consisting of a positive health intake with goal setting, multidisciplinary meetings, a personalised care plan and proactive care management. The study will conclude with a follow-up (2–8 months), resulting in a total study duration of 22 months. We plan to include 200 patients with (a) problems on two or more life domains and (b) at least two acute care encounters in the previous year. Possible Hotspotters are identified using an Adjusted Clinical Groups-based algorithm or via a local primary healthcare team.

Questionnaires and routine care data will be used to gather data on cost-effectiveness, which will then be assessed using multilevel analysis, with levels for the individual, cluster and duration of control period. Secondary outcomes will include psychological outcomes on self-regulation (proactive coping, patient activation, self-efficacy and intention), experience of care (satisfaction, perceived autonomy support and qualitative data from focus groups) and quality of life, qualitative analysis of the Positive Health approach, implementation outcomes and process evaluation including integration of care.

The Ethics Committee of Leiden University Medical Centre granted approval (METC-LDD, P21.123). Results will be shared through peer-reviewed publication and (inter)national conference presentations.

NCT05878054.

Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more spontaneous pregnancy losses from the time of conception until 24 weeks of gestation. Currently, an underlying cause can be identified in only a minority of the losses. Potentially, an impaired maternal immune response targeting the semiallograft pregnancy may lead to miscarriage. While prior studies have explored the use of immune-suppressing corticosteroids to modulate the maternal immune system and hopefully improve pregnancy outcome, the absence of sufficiently powered randomised controlled trials (RCT) underscores the need for further research. The primary aim of this study is to evaluate if prednisolone administration in early pregnancy (20 mg daily for 6 weeks, then tapering doses for 2 weeks) in women with unexplained RPL leads to a higher live birth rate (LBR) in comparison to placebo. Additionally, the study assesses the tolerability, safety and the cost-effectiveness of this intervention. Finally, we will explore the effect of prednisolone in various subgroups (based on maternal age, number of previous pregnancy losses, presence of specific antibodies and pre-pregnancy endometrial immune cell level).

This ongoing multicentre, double-blind RCT will randomise 490 women with unexplained RPL and pregnancy

This study was submitted under the Clinical Trial Regulation (CTR) in Clinical Trials Information System (CTIS) for assessment by the Central Committee on Research Involving Human Subjects (CCMO) under Clinical Trial number: 2023-503220-76-01. It received full approval on 29/01/2024. Study findings will be presented at conferences and published in a peer-reviewed journal. Participants will be informed about the results by publishing them on the publicly available website of the study.

This trial is registered in ClinicalTrials.gov (ID NCT05725512) and in CTIS (2023-503220-76-01).