The Puerto Rico Department of Health (PRDH) seeks to identify dengue epidemics as early as possible with high specificity.

Development and prospective application of an early warning system for dengue epidemics using routine historical surveillance data. A weekly intercept-only negative binomial regression model was fitted using historical probable and confirmed dengue data. A range of threshold definitions was explored using three model-estimated percentiles of weekly dengue case counts.

Dengue is endemic in Puerto Rico with irregular occurrence of large epidemics with substantial impact on health burden and health systems. Probable and confirmed dengue data are routinely collected from all hospitals and private clinics.

A total of 86 282 confirmed or probable dengue virus cases were reported from 1 January 1986 to 30 June 2024, with an annual mean of 2212 cases (median: 1533; range: 40–10 356).

The model was fitted retrospectively to mimic real-time epidemic detection and assessed based on sensitivity and specificity of epidemic detection.

The 75th percentile threshold aligned best with historical epidemic classifications, balancing false alarms and missed detections. This model provides a robust method for defining thresholds, accounting for skewed data, using all historical data and improving on traditional methods like endemic channels.

In March 2024, PRDH declared a public health emergency due to an early, out-of-season surge in cases that exceeded the epidemic alert threshold developed in this study. This real-time application highlights the value of these thresholds to support dengue epidemic detection and public health response. Integrating thresholds with other tools and strategies can enhance epidemic preparedness and management.

Digital inclusion (which includes skills, accessibility and connectivity to the internet and digital devices) is a ‘super social determinant of health’ because it affects many aspects of life that influence health. Older people are especially vulnerable to digital exclusion. Existing digital inclusion interventions are commonly offered opportunistically to people who come into contact with services, or in specific locations. The lack of systematic identification of need unintentionally excludes older people who may be most in need of support, and that support is not addressing their needs.

This multi-method project includes six workstreams: (1) A survey of people aged 65+ to ask about digital use and engagement. Survey data will be used to develop a model that predicts digital exclusion from data available in primary care records. (2) Testing, via a further survey, the external validity of the model to identify those who are digitally excluded. (3) Interviews with community service providers to identify, understand and define the components of existing digital inclusion services for older people. Concurrently, a rapid review of the literature will identify evidence for interventions aimed at supporting digitally excluded adults aged 65+. (4) Interviews with people aged 65+ representing a range of digital use will explore factors from the COM-B model that influence digital behaviours—their capability (C), opportunity (O) and motivation (M) relating to digital engagement. Analysis outputs will identify the intersectional nature of barriers or facilitators to digital inclusion. (5) Co-production workshops with older people and community service providers will identify key components of interventions that are required to address digital exclusion. Components will be mapped against existing interventions, and the ‘best fit’ intervention(s) refined. An implementation plan will be developed in parallel. (6) Feasibility testing of the refined intervention(s) to assess acceptability and obtain feedback on content and delivery mechanisms.

This study was approved by the Yorkshire & The Humber - Bradford Leeds Research Ethics Committee on 23 October 2023 (ref. 23/YH/0234). Findings will be disseminated in academic journals and shared at webinars, seminars, conferences and events arranged by organisations operating across the digital inclusion and older people fields.

https://www.isrctn.com/ISRCTN18306736

To describe the prevalence of cardiovascular disease (CVD) at the time of diagnosis of adult-onset type 1 (T1D) and type 2 (T2D) diabetes, in a recent cohort and compare to a previous cohort from the same region. Further, to explore factors influencing the prevalence of pre-existing CVD, including age, sex, body mass index (BMI) and C-peptide; in the later cohort also heart failure, hyperlipidaemia, tobacco use and physical activity.

Two prospective cross-sectional cohort studies compared.

All primary health care centres and hospitals in Kalmar and Kronoberg counties in Southeastern Sweden.

Adults with newly diagnosed T1D or T2D (classified by combination of islet antibodies and C-peptide) in 1998–2001 and 2016–2017.

Prevalence of hypertension and CVD at diagnosis of diabetes, and associations with beta-cell function, in two cohorts collected 15 years apart. Further, to explore factors influencing the prevalence of hypertension and CVD, and level of C-peptide.

In patients with newly diagnosed T2D, mean age-at-onset had decreased (66±14.1 years vs 63±12.6, p≤0.001) and mean BMI had increased (29.0±5.4 vs 31.4±5.8 kg/m², p≤0.001). Prevalence of pre-existing myocardial infarction had decreased in both T1D (18% vs 7%, p=0.03) and T2D (25% vs 11%, p≤0.001). Pre-existing hypertension had increased in both T1D (23% vs 40%, p=0.01) and T2D (44% vs 61%, p≤0.001). C-peptide level was lower and was associated with several cardiovascular conditions in newly diagnosed T2D in 2016–2017 (p=0.048 p≤0.001).

Patients with newly diagnosed T2D were younger, with higher BMI, compared with 15 years earlier, a challenge for diabetes care. Prevalence of pre-existing myocardial infarction had decreased notably, in line with, but still less than in the general population; while pre-existing hypertension had increased, in both diabetes types. C-peptide was associated with several cardiovascular conditions in newly diagnosed T2D in the recent cohort, which warrants further investigation.

Atopic dermatitis (AD) is a chronic, relapsing, heterogeneous skin disease affecting 2%–7% of adults, with roughly 30% having moderate-to-severe disease. AD symptoms, like intense itching and skin pain, carry a substantial disease burden that negatively impacts patients’ quality of life (QoL) and psychosocial well-being. Lebrikizumab is a novel, high-affinity monoclonal antibody that selectively binds to and neutralises interleukin-13 with high potency. Three clinical trials with lebrikizumab (ADvocate 1 and 2; ADhere) demonstrated significant clinical benefit in patients with AD, while the 3-year long-term extension study of lebrikizumab (ADjoin) further demonstrated long-term efficacy and safety in patients with AD. The ADTrust study will evaluate patient well-being, their relationship with their skin, long-term effectiveness, and safety of lebrikizumab, treatment satisfaction, and long-term effect of lebrikizumab treatment on different aspects of patients’ lives, including itch, pain, sleep, fatigue, work impairment and overall QoL among adult patients with moderate-to-severe AD in a real-world setting.

This non-interventional, prospective, observational, real-world evidence study will involve approximately 150 sites across Europe and approximately 1200 adults with moderate-to-severe AD treated with lebrikizumab for 2 years. The primary endpoint is patient well-being assessed by the 5-item WHO Well-Being Index (WHO-5) questionnaire. Key secondary endpoints include clinical effectiveness (Eczema Area and Severity Index and Investigator’s Global Assessment Scale), disease symptomatology and control (Patient-Oriented Eczema Measure, 24-hour peak pruritus, skin pain, fatigue and sleep quality Numerical Rating Scale, and safety and tolerability. Other validated endpoints will evaluate physician-reported and patient-reported QoL and treatment satisfaction (Dermatology Life Quality Index, Treatment Satisfaction Questionnaire-9), patients’ work productivity and impairment (Work Productivity and Activity Impairment (WPAI)-AD) and disease control (AD Control Tool). Novel experimental endpoints will also be evaluated with the aim to assess patients’ relationship with their skin (SkinLove questionnaire), disease control (intensity and frequency of flares) and an Effectiveness Diary^+© (a brief monthly survey on a voluntary basis with the aim to assess the long-term impact of lebrikizumab on three fundamental aspects of the patients’ life: the well-being (WHO-5), the itch intensity (24 hours peak pruritus) and the frequency and intensity of flares). Statistical analyses will be descriptive and explorative and based on observed cases. Missing data imputation may be used to handle missing data for primary endpoints and secondary effectiveness endpoints.

This study will be conducted according to the protocol, which has ethics committee approval (Hamburg Ethic Committee in Germany: 2024-101358-BO-ff), and all applicable laws and regulatory requirements for each participating country. The results will be disseminated through scientific publications and congress presentations.

NCT06815380 (Pre-results).

Model-based cost-effectiveness analysis (CEA) of pharmaceuticals informs reimbursement and pricing in many healthcare systems, and it is essential that CEA evidence is valid and reliable. Several studies have reported lacking transparency in CEA studies. In this study protocol, we describe a study that will investigate whether model-based CEA studies of cancer drugs are transparent and informative enough to enable the reproduction of study findings.

This study protocol outlines a study where we will identify CEA studies indexed in MEDLINE from 2015 to 2023 based on predefined search terms. We will include English-language CEA studies evaluating pharmaceutical treatments based on decision-analytical modelling methods that report cost-effectiveness results using life-years, quality-adjusted life-years and/or disability-adjusted life-years as health outcome metric(s). Two authors will screen abstracts and full text for inclusion. We anticipate that a maximum of 150 studies will be included after a full-text review. A data extraction template is designed to capture information used to determine reproducibility together with other information that will be analysed as potential determinants of reproducibility in logistic and linear regression analyses.

This study design has been deemed exempt from ethical approval. All collected data will be made available in an online repository that will host the study protocol and other supplementary data. Results from this proposed study will be published in peer-reviewed journals and at scientific conferences and workshops.

Breast cancer-related lymphoedema (BCRL) at the arm and/or trunk/breast is a highly feared complication following breast cancer treatment and can be objectified using the state-of-the-art criteria based on volume, extracellular water ratio or skin thickness measurements. Although the incidence of objective BCRL is decreasing due to advances in breast cancer treatment, many patients report a sensation of swelling without the presence of objective BCRL, referred to as subjective BCRL. As little is known about the prevalence and the transitions between different BCRL states (no-subjective-objective) over time, as well as about the underlying mechanisms and contributing factors of subjective BCRL, this will be investigated in the LymphSens study.

230 patients with a new diagnosis of unilateral breast cancer will be included in a multicentre longitudinal study. Measurements are performed from presurgery to 12 months postsurgery. The primary objective (aim 1) is to determine the prevalence rate of subjective and objective BCRL at 1, 6 and 12 month(s) postsurgery, as well as transitions between BCRL states (no-subjective-objective BCRL) by a multinomial logistic regression model with generalised estimating equations and transition matrices, respectively. A second objective (aim 2) is to determine factors related to four potential underlying mechanisms (lymphatic, nociceptive, neuropathic and central sensory processing problems) that contribute to the occurrence of subjective BCRL in comparison with no self-reported swelling and objective BCRL. As a third objective (aim 3), within the group of patients with subjective BCRL, we will determine factors related to these four underlying mechanisms that contribute to the severity of subjective BCRL. The analyses for aim 2 and aim 3 will be conducted both at specific time points, that is, 1, 6 and 12 month(s) postsurgery using exploratory analysis and across all time points collectively using multivariable binary logistic regression models or multivariable longitudinal models for repeated measures.

The LymphSens study protocol received approval from the Ethics Committee of UZ Leuven (S68133) and UZ Antwerp/University of Antwerp (5676-003252). The results of the LymphSens study will be presented at conferences and published in peer-reviewed journals.

NCT06324721.

This study aimed to explore what intervention specificities or attributes newly diagnosed individuals with multiple sclerosis (MS) find important and to explore possible reasons behind their evaluations.

A stepwise approach began with a systematic literature review to identify significant attributes. Patients with MS then assessed these attributes through an online survey, which included a ranking exercise and open-ended questions. Finally, the results were evaluated by the clinical team to select the most relevant factors for personalised care.

From June 2023 to December 2023, all consecutive patients referred to the MS Center of Careggi University Hospital were screened for inclusion. Following recruitment, cognitive and physical assessments were administered at the Don Gnocchi Centre. All participants were interviewed by an experienced neuropsychologist.

Participants were enrolled in the RELIABLE clinical trial, which included a ranking exercise and open-ended question. In the ranking exercise, patients prioritised levels of treatment attributes: treatment effects, methods of intervention, type of monitoring, monitoring, mode and mental support. The open-ended questions addressed the reasons behind the level rankings.

Participants’ rankings revealed the most important levels of each attribute. The highest-ranked method of intervention was disease-modifying treatment, which received 164 points. For mental support, individual psychotherapy was deemed most important with 149 points. Preservation of cognitive function, a key treatment effect, received 144 points. Clinical check-ups were the top type of monitoring with 129 points. Lastly, the hybrid mode of monitoring (half remote/half in-person) was ranked with 77 points. Open-ended responses provided insights into the reasons behind these preferences, emphasising the importance of maintaining mobility, cognitive function and emotional well-being. The clinical team evaluated these findings, confirming that the selected attributes were both clinically relevant and aligned with patient priorities. This evaluation process ensured that the treatment specificities chosen for individualised care were comprehensive and reflective of patient needs.

By identifying and prioritising key treatment attributes, this research highlights the multifaceted nature of MS management and emphasises the importance of aligning treatment options with patient preferences. Addressing these factors through further quantitative preference assessments is essential for preventative MS care, improving patient outcomes and promoting a more patient-centred approach to treatment.

Many women need to use medications during breastfeeding. Very few medications have been adequately monitored, tested and labelled with safety information for this use. Prednisolone is one of these drugs. We aim to conduct a multicentre low-intervention clinical trial to determine the concentration of prednisolone in plasma of breastfed infants of lactating women treated with prednisolone. In addition, we will measure the concentration in maternal plasma and breast milk and calculate the daily infant dose (DID) and relative infant dose (RID). Infant cortisol levels will be analysed as a measure of clinical effects in the infants.

The study will be conducted at departments of obstetrics and gynaecology and specialist maternity and paediatric outpatient clinics in Sweden. We aim to include 30 lactating women treated with prednisolone and their breastfed infants. Breast milk and blood will be collected merely to study the secretion of prednisolone into breast milk and transfer to the infant. Participants will be treated with prednisolone according to their physician’s prescription. Study visits take place when the infant is approximately 6–8 weeks old. Milk and blood sampling of the mother will be performed at 1 hour after drug intake, in conjunction with the infant being fed. Blood sampling of the infant will be performed 2 hours after the feed. Breast milk and plasma will be biobanked for future research. Recruitment was initiated in 2024 and is ongoing. Patient representatives from the Swedish Rheumatism Association were involved in the planning of the study, and the organisation is providing information about the study on their website.

The clinical trial was approved by the Swedish Medical Product Agency (Dnr. 5.1.1-2023-104170). The results will be published in peer-reviewed scientific journals and disseminated at scientific meetings and through patient organisations’ websites.

The clinical trial protocol is available via the Clinical Trial Information System at the European Medicines Agency (No. 2023-508913-18-00). It is also registered and publicly accessible at the EU PAS Register (EUPAS 1000000059).

As the global population ages, the incidence of cardiometabolic diseases and associated healthcare costs rise. There is a critical need for preventive interventions enabling long-lasting treatment effects to address the decline in physical performance and metabolic health among older adults. The RESTART (RE-inventing Strategies for healthy Ageing: Recommendations and Tools) randomised controlled trial (RCT) aims to evaluate whether a complex lifestyle intervention can improve and maintain cardiorespiratory fitness, muscle strength and body composition among older adults with elevated cardiometabolic risk.

This is the study protocol for the RESTART trial, a two-arm, open-label, parallel-group RCT conducted in Tromsø, Norway, targeting adults aged 60–75 with obesity, a sedentary lifestyle and high cardiovascular risk. Participants are block-randomised (1:1) into either an intervention or active control group. The initial intervention phase (12 months) includes: (a) supervised high-intensity aerobic and strength training (≥85% of maximum capacity) performed two times weekly, (b) behavioural counselling based on acceptance and commitment therapy during six group sessions and (c) dietary guidance based on national nutrition recommendations during two group/two individual sessions. After 12 months, participants are gradually introduced to exercise sessions offered by local organisations and fitness centres, to enable independent maintenance of lifestyle change. The primary outcome is a change in cardiorespiratory fitness (VO_2max) at 24 months. Secondary and tertiary outcomes include additional parameters potentially sensitive to lifestyle change, such as 1-repetition maximum muscle strength, muscular power, device-measured physical activity levels, body composition, waist circumference, body weight, cognitive function and self-reported health-related quality of life. Data collection is scheduled at baseline, 6, 12 and 24 months, with health economic and qualitative analyses to evaluate the intervention’s impact and participant experiences.

Ethical approval for the RESTART trial was obtained from the Regional Committee for Medical Research Ethics in Northern Norway. Results will be disseminated through peer-reviewed publications, conferences and community-based channels targeting older adults, healthcare providers and municipal health organisations. This trial will also inform public health strategies for lifestyle interventions among ageing populations.

NCT06122441.