Sodium-glucose cotransporter (SGLT) inhibitors have shown substantial benefit in reducing cardiovascular and kidney events across diverse clinical populations, but the underlying physiological mechanisms remain unclear. However, existing mechanistic studies on renal and cardiovascular haemodynamics show variability in design, have limited statistical power and yield inconsistent outcomes, thus limiting the ability to draw generalisable conclusions. To address this gap, we conducted a systematic review and proposed the first meta-analysis to aggregate individual participant-level data from mechanistic studies to identify consistent physiological patterns and enhance understanding of the therapeutic effects of SGLT inhibition.

Gold-standard measured glomerular filtration rate (mGFR) was selected as the primary outcome for this systematic review, which aimed to identify all completed mechanistic studies investigating the effects of SGLT inhibition. Electronic databases including Ovid MEDLINE; Ovid Embase; Cochrane Database of Systematic Reviews; and Cochrane Central Register of Controlled Trials were searched using a detailed search strategy. In total, 24 studies (n=1296) were identified. This systematic review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Key variables including demographics, medical history, concomitant medications, vital signs, mGFR, renal haemodynamics, urine and plasma biochemistry, tubular sodium handling, echocardiography, cardiac output monitoring, arterial stiffness and fluid volume will be extracted. A one-stage individual participant data meta-analysis under a Bayesian framework will be conducted, using hierarchical models to simultaneously analyse data from all eligible studies. The risk of bias due to missing results will be assessed. Sensitivity analyses and subgroup evaluations will be incorporated to explore sources of heterogeneity and assess robustness of findings.

Ethics approval was obtained from University Health Network, Toronto, Canada. Findings from the Mechanisms of SGLT Inhibitor Action and Physiological Mediators (MOSAIC) meta-analysis will be published in peer-reviewed journals and results will be disseminated at scientific conferences.

CRD420251001413.

To explore how sexuality and sexual boundary violations are perceived and experienced in healthcare teams and organisations.

Qualitative focus group study.

Mental health and disability care.

In total, 56 people participated across 15 focus groups in three healthcare organisations. Participants included client experts (former clients), healthcare professionals such as a psychologist, speech therapist, sexologist and personal coach, team leaders, managers and directors.

We identified 14 different types of situations in which sexuality and sexual boundary violations play a role on four different levels: between clients, between clients and healthcare professionals, between healthcare professionals and on the management level. Situations ranged from attraction and intimacy between clients and/or professionals, promoting sexual health of clients, gut feelings and speaking up, transgressive behaviour from clients and professionals, false accusations and investigations into allegations.

Situations regarding sexuality and sexual boundary violations are varied and complex. They unfold at different levels of interaction within the organisation. To deal with this and come to practical approaches, it is important that clients, professionals and managers engage in reflection and dialogue about their experiences, opinions and perspectives.

Rapid identification of high-risk and low-risk patients presenting to the emergency department (ED) influences clinical management and can help optimise patient outcomes as well as resource allocation. This study aims to externally validate the Risk Stratification in the Emergency Department in Acutely Ill Older Patients (RISE UP) score in adult patients in the ED with suspected infection. Furthermore, generalisability was assessed by comparing the discriminatory ability of the RISE UP with the quick Sequential Organ Failure Assessment (qSOFA) as well as the Modified Early Warning Score (MEWS) and National Early Warning Score (NEWS).

Retrospective cohort study.

Single-centre study in the ED of a tertiary, university-affiliated hospital.

Adult patients with suspected infection presenting at the ED for internal medicine from 2016 to 2022.

The primary outcome was all-cause 30-day mortality. Secondary outcomes were all-cause 14-day mortality, 7-day mortality and intensive care unit (ICU) admission.

Prognostic performance was evaluated using discrimination (area under the receiver operating characteristic curve (AUC)) and a calibration plot.

Of the included 5038 ED visits, there was a 30-day mortality of 7.1%. Discrimination of RISE UP for 30-day mortality was good (AUC 0.809; 95% CI 0.786 to 0.832) and significantly higher than that for the other risk scores: qSOFA (AUC 0.675; 95% CI 0.644 to 0.707), MEWS (AUC 0.688; 95% CI 0.658 to 0.718) and NEWS (AUC 0.725; 95% CI 0.696 to 0.754) (p

The RISE UP score outperformed the qSOFA, MEWS and NEWS in predicting 30-day mortality. It is generalisable to an adult infection-specific cohort and may facilitate distinction between high-risk and low-risk patients in the ED, particularly to rule out poor outcomes.