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310 records · Page 18Linked to original sources

Development and validation of a comprehensive prognostic model for 28-day ICU mortality in non-traumatic subarachnoid hemorrhage: an analysis based on the MIMIC-IV database.

BACKGROUND: Due to the complex pathophysiology of non-traumatic subarachnoid hemorrhage (SAH), accurate risk prediction remains a challenge. Our aim is to develop and validate a comprehensive prognostic model that integrates demographic characteristics, vital signs, laboratory parameters, and more, to provide clinical decision-making support in real-world practice. METHODS: We conducted a retrospective cohort study of 785 Non-traumatic subarachnoid hemorrhage patients. The cohort was randomly divided into a training set (n = 549) and a validation set (n = 236). Feature selection was performed using LASSO regression, followed by backward stepwise Cox regression for optimization. A nomogram was constructed based on independent predictive factors, and model performance was assessed using discrimination, calibration, and decision curve analysis. To prevent immortal-time bias, all predictors were anchored to a fixed early (first-24-hour) measurement window, treatment variables were modelled as binary indicators rather than cumulative exposures, and a five-model sensitivity analysis with baseline-severity adjustment was performed. RESULTS: The development of our model followed a systematic approach: first, 15 potential predictive factors were selected via LASSO regression, which were then refined to 12 independent predictors using backward stepwise Cox regression. The final predictive factors included: Ventilation, AHT, Nimodipine 60 mg, Age, SAPS.II, Input amount, Calcium total, Platelet count, White blood cells, Anion gap, pH, and Chloride. The integrated model demonstrated excellent predictive ability for 7-day, 14-day, and 21-day mortality in both the training set (AUC: 0.972, 0.934, 0.898) and the validation set (AUC: 0.968, 0.948, 0.911). Calibration curves and decision curve analysis confirmed the model's reliability and clinical utility across different time points. We constructed a nomogram for individualized risk prediction. Univariate Kaplan-Meier survival analysis demonstrated significant stratification of survival outcomes by each predictor, while restricted cubic spline analysis revealed non-linear relationships between continuous variables and mortality risk. Random survival forest analysis identified the top three predictive factors (Nimodipine 60 mg, Ventilation, AHT) and compared them with our full 12-variable model, confirming superior performance of the integrated model at all time points. At the 28-day primary endpoint, the model achieved a time-dependent AUC of 0.898 (training) and 0.904 (validation); after restricting predictors to the early baseline window, the leakage-controlled model retained good discrimination (validation C-index 0.803). CONCLUSIONS: Our ICU 28-day mortality prognosis model demonstrated robust performance in predicting ICU 28-day mortality in non-traumatic subarachnoid hemorrhage. The model, through the nomogram, provides individualized risk assessment, aiding clinical decision-making and patient stratification.

Humans

Smoke-Free Home Intervention in Permanent Supportive Housing: A Cluster Randomized Clinical Trial.

IMPORTANCE: Chronic diseases related to tobacco use and secondhand smoke exposure are the leading causes of death among formerly homeless adults living in permanent supportive housing (PSH) in the US. OBJECTIVE: To evaluate the efficacy of a brief, smoke-free home intervention in promoting voluntary smoke-free home adoption among PSH residents. DESIGN, SETTING, AND PARTICIPANTS: In this cluster randomized clinical trial, data collection occurred from January 11, 2022, to March 31, 2025. Participants were residents aged 18 years or older who smoked cigarettes at home in 40 multiunit PSH sites in the San Francisco Bay area, randomized to intervention or waiting list control clusters, and housing staff who worked at the study sites. INTERVENTION: Residents in intervention sites received one-on-one in-person coaching from research staff on adopting a smoke-free home; waiting list control site residents received no interventions during the study but were offered the intervention once the intervention group completed follow-up. Staff in both intervention and control sites received training on providing brief tobacco cessation coaching. MAIN OUTCOMES AND MEASURES: Primary outcomes were smoke-free home adoption for at least 90 days and 7-day carbon monoxide-verified point prevalence abstinence (PPA; expired carbon monoxide level ≤5 ppm) at 6 months. Secondary outcomes were any adoption (≥1 day) of a smoke-free home in the past 90 days among residents and changes in Smoking Knowledge, Attitudes, and Practices (S-KAP) scores among staff. RESULTS: The trial enrolled 400 residents (mean [SD] age, 54.5 [10.7] years; 251 [63.1%] male), 191 in the intervention and 209 in the control cluster. At 6 months, 13 residents (6.8%) in the intervention and 10 (4.8%) in the control group adopted a smoke-free home for at least 90 days (odds ratio [OR], 1.45; 95% CI, 0.69-3.07). Few residents achieved 7-day PPA, though more intervention residents (12 [6.3%]) achieved it compared with controls (2 [1.0%]) (OR, 6.94; 95% CI, 1.69-28.45). Intervention residents had greater odds than control residents of any smoke-free home adoption of at least 1 day (121 [63.4%] vs 77 [36.8%]; adjusted OR, 3.83 [95% CI, 2.63-5.57]). Among staff, mean (SD) S-KAP scores increased at 6 months vs baseline for beliefs (by 0.21 [0.55] points) and practices (by 0.24 [0.61] points) pertaining to providing cessation treatment. CONCLUSIONS AND RELEVANCE: In this cluster randomized clinical trial, the brief intervention did not result in a significant increase in smoke-free home adoption for at least 90 days, though more residents in the intervention than the control group attempted adoption for at least 1 day. These findings support the scalability of this approach to reduce smoking in PSH, but more intensive interventions may be needed to sustain intervention effects. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04855357.

Humans

Ketoacidosis with SGLT2 inhibitors in routine clinical practice of type 2 diabetes: Scandinavian cohort and nested case-control study.

BACKGROUND: SGLT2 inhibitors increase the risk of ketoacidosis, but data from routine clinical practice are scarce. We used nationwide registers with the aim of assessing the incidence, risk factors, and prognosis of ketoacidosis during SGLT2 inhibitor treatment in patients with type 2 diabetes. METHODS: In this cohort and nested case-control study we used data from three Scandinavian countries. In a cohort of SGLT2 inhibitor-treatment episodes among patients with type 2 diabetes aged at least 18 years in Sweden, Denmark, and Norway, we estimated ketoacidosis incidence. Using a nested case-control design (matched on age, sex, region of birth, calendar time, and time since treatment initiation), we assessed risk factors and precipitating or co-occurring events. Changes in diabetes medications were evaluated. FINDINGS: The study period was Jan 1, 2013, to Dec 31, 2021, in Denmark and Sweden, and Jan 1, 2013, to Dec 31, 2022, in Norway. We included 322&#x2008;597 treatment episodes among 282&#x2008;282 patients with type 2 diabetes (mean age 63 years, 116&#x2008;521 [36&#xb7;1%] of 322&#x2008;597 women). During a median (IQR) follow-up of 1&#xb7;3 (0&#xb7;7-2&#xb7;8) years, 1452 ketoacidosis events occurred (incidence 2&#xb7;43 per 1000 person-years). Although highest shortly after initiation, risk persisted throughout follow-up. Strong risk factors included high HbA1c (&#x2265;83 vs &#x2264;52 mmol/mol: odds ratio [OR] 15&#xb7;37 [95% CI 11&#xb7;50-20&#xb7;53]), malnutrition (OR 10&#xb7;54 [7&#xb7;32-15&#xb7;18]), previous ketoacidosis (OR 10&#xb7;40 [7&#xb7;09-15&#xb7;24]), low BMI (<20 kg/m2vs 20 to <25 kg/m2: OR 9&#xb7;98 [5&#xb7;68-17&#xb7;53]), and recent hypoglycaemia (OR 5&#xb7;22 [2&#xb7;60-10&#xb7;49]). Infection was the most common precipitating or co-occurring event (454 [31&#xb7;8%] of 1428 vs 862 [6&#xb7;1%] of 14&#x2008;233 for ketoacidosis cases vs controls; OR 7&#xb7;60 [6&#xb7;62-8&#xb7;71]). The strongest associations were observed for alcohol intoxication, acute renal events, acute abdomen, stroke, and major surgery, although associations for some transient exposures, particularly milder conditions, might have been overestimated because of under-registration among controls. Exploratory analyses suggested that the observed associations were largely general to patients with type 2 diabetes rather than specific to SGLT2 inhibitor use. At 1 year after ketoacidosis, 211 (25&#xb7;1%) of 842 remained on SGLT2 inhibitors and insulin use increased from 269 (31&#xb7;9%) of 842 to 615 (73&#xb7;0%) of 842. INTERPRETATION: Ketoacidosis risk with SGLT2 inhibitors varies greatly by patient characteristics and is not confined to early in treatment. Risk should be assessed throughout treatment, and patients should be instructed to pause treatment during acute illness and stress. FUNDING: Region Stockholm, Swedish Society of Medicine, Karolinska Institutet.

Journal Article

Once-weekly IcoSema versus once-daily insulin glargine U100 in type 2 diabetes management (COMBINE 4): an open-label, multicentre, treat-to-target, randomised, phase 3b trial.

BACKGROUND: Stepwise treatment intensification is recommended for managing type 2 diabetes, including insulin initiation when non-insulin glucose-lowering medications are insufficient. Guidelines recommend combining a GLP-1 receptor agonist with basal insulin to improve glycaemic efficacy while reducing weight gain and hypoglycaemia risk. COMBINE 4 evaluated the efficacy and safety of IcoSema, a once-weekly combination therapy of basal insulin icodec and semaglutide (a GLP-1-receptor agonist) versus insulin glargine U100 (glargine U100) in people with type 2 diabetes on oral glucose-lowering medications. METHODS: COMBINE 4 was a 40-week, randomised, open-label, treat-to-target, phase 3b trial conducted across 97 sites in nine countries. Adults (aged &#x2265;18 years) with type 2 diabetes (HbA1c &#x2265;8&#xb7;0%) receiving oral glucose-lowering medications were randomly allocated in a 1:1 ratio without stratification to IcoSema or once-daily glargine U100. The titration target was 3&#xb7;9-5&#xb7;0 mmol/L (70-90 mg/dL). The primary endpoint was change in HbA1c and the secondary confirmatory endpoint was change in bodyweight, both from baseline to week 40, evaluated in all randomly allocated participants. Adverse events were recorded during weeks 0-45. This trial is registered with ClinicalTrials.gov (NCT06269107) and is complete. FINDINGS: Of 653 individuals screened between Feb 15 and Aug 6, 2024, 151 did not meet screening criteria and 17 withdrew before initiating treatment; 243 were randomised to IcoSema and 242 to glargine U100. Of the 485 randomly allocated participants, 286 (59%) were male and 199 (41%) were female, and median age was 58 years (range 26-82). For HbA1c, from baseline (9&#xb7;57% for IcoSema and 9&#xb7;50% for glargine U100), mean change to week 40 was greater with IcoSema versus glargine U100 (-3&#xb7;32 vs -2&#xb7;44 percentage points; estimated treatment difference [ETD] -0&#xb7;88 percentage points [95% CI -1&#xb7;12 to -0&#xb7;63]), confirming superiority of IcoSema (p<0&#xb7;001). From baseline to week 40, mean bodyweight decreased with IcoSema and increased with glargine U100 (-0&#xb7;79 vs 3&#xb7;81 kg; ETD -4&#xb7;61 kg [95% CI -5&#xb7;46 to -3&#xb7;75]), confirming superiority of IcoSema (p<0&#xb7;001). Rate of combined clinically significant (blood glucose <3&#xb7;0 mmol/L [<54 mg/dL], confirmed with a blood glucose meter) or severe hypoglycaemia (severe cognitive impairment requiring external assistance for recovery) was statistically significantly lower with IcoSema versus glargine U100 (0&#xb7;29 vs 0&#xb7;59 episodes per person-year of exposure; estimated rate ratio 0&#xb7;56 [95% CI 0&#xb7;32 to 0&#xb7;97]; p=0&#xb7;04). Gastrointestinal disorders were the most frequently reported adverse events with IcoSema. INTERPRETATION: Once-weekly IcoSema demonstrated superior HbA1c reduction and bodyweight change, with lower rates of clinically significant or severe hypoglycaemia, versus glargine U100, suggesting that IcoSema might be an effective once-weekly treatment option for insulin-naive individuals with type 2 diabetes inadequately controlled on oral glucose-lowering medications. FUNDING: Novo Nordisk.

Humans