Risultati per: L'automisurazione della pressione arteriosa: I target pressori

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Large administrative databases hold promise for advancing biomedical care, like sails awaiting the winds of a clinically relevant question to navigate uncharted waters. However, making best use of those data for causal questions requires careful study design and analysis. Taking the helm, Alwang and colleagues have performed a multicenter, retrospective cohort and target trial emulation study (which seeks to emulate a randomized clinical trial [RCT]) to evaluate the comparative effectiveness of intravenous (IV) lactated Ringer vs normal saline in hospitalized patients with sickle cell disease (SCD) during vaso-occlusive episodes (VOEs), reported in JAMA Internal Medicine.

Annals of Internal Medicine, Ahead of Print.

Annals of Internal Medicine, Ahead of Print.

Objective
We assessed the association of early statin initiation with inpatient mortality among hospitalised COVID-19 patients.

Design, setting and participants
This observational study emulated a hypothetical target trial using electronic health records data from Northwestern Medicine Health System, Illinois, 2020–2022. We included patients who were ≥40 years, admitted ≥48 hours for COVID-19 from March 2020 to August 2022 and had no evidence of statin use before admission.

Interventions
Individuals who initiated any statins within 48 hours of admission were compared with individuals who did not initiate statins during this period.

Primary outcome measures
Inpatient mortality at hospital days 7, 14, 21 and 28 were determined using hospital records. Risk differences between exposure groups were calculated using augmented inverse propensity weighting (AIPW) with SuperLearner.

Results
A total of 8893 individuals (24.5% early statin initiators) were included. Early initiators tended to be older, male and have higher comorbidity burdens. Unadjusted day 28 mortality was higher in early initiators (6.0% vs 3.6%). Adjusted analysis showed slightly higher inpatient mortality risk at days 7 (RD: 0.5%, 95% CI: 0.2 to 0.8) and 21 (RD: 0.6%, 95% CI: 0.04 to 1.1), but not days 14 (RD: 0.4%, 95% CI: –0.03 to 0.9) and 28 (RD: 0.4%, 95% CI: –0.2 to 1.1). Sensitivity analyses using alternative modelling approaches showed no difference between groups.

Conclusions
Early statin initiation was not associated with lower mortality contrasting with findings of previous observational studies. Trial emulation helped in identifying and addressing sources of bias incompletely addressed by previous work. Statin use may be indicated for other conditions but not COVID-19.

Introduction
Continuous renal replacement therapy (CRRT) is a critical therapeutic intervention for patients with severe acute kidney injury in intensive care. However, premature filter clotting remains a significant challenge during CRRT, impacting treatment efficacy, costs and patient outcomes. Anticoagulation is essential to maintain circuit patency, with regional citrate anticoagulation (RCA) emerging as a preferred strategy due to its favourable bleeding profile. The standard target for post-filter ionised calcium (iCa) concentration during RCA-CRRT is set between 0.25 and 0.35 mmol/L, although evidence supporting this range is limited. We hypothesise that a higher post-filter iCa target (0.35–0.45 mmol/L) can provide comparable circuit patency while potentially reducing adverse effects associated with citrate administration.

Methods and analysis
This multicentre randomised controlled non-inferiority trial will compare a low post-filter iCa target (0.25–0.35 mmol/L) with a higher post-filter iCa target (0.35–0.45 mmol/L) in patients undergoing RCA-CRRT in the intensive care unit. A total of 412 CRRT sessions will be randomised with a 1:1 ratio into these two groups. The primary outcome is the incidence of filter clotting. Secondary outcomes include filter lifespan, post-filter iCa levels, citrate infusion rates, the occurrence of metabolic adverse effects, financial costs and blood loss.

Ethics and dissemination
The study has obtained approval from the ethics committee (Ethics Committee Est III, Nancy, France) and patients will be included after providing informed consent. The results will be disseminated at academic conferences and in peer-reviewed publications. All procedures were developed in order to assure data protection and confidentiality.

Trial registration number
NCT05814341.

Introduction
Very preterm babies are at risk of poor neurodevelopmental outcomes and death. Intraventricular haemorrhage (IVH) after birth is the most prevalent cause of this. Birth by caesarean section may protect against IVH in very preterm babies, but the evidence is limited. The aim is to identify and obtain the quantitative evidence needed to inform a future definitive clinical trial to determine the optimal mode of delivery in preterm birth.

Methods and analysis
We will use three broad workstreams (WS) to answer complementary questions. WSs 1 and 2 involve the analysis of routinely recorded national clinical data held in an established research database. In WS1 (October 2023–March 2024), we will use conventional methods to identify what is needed to undertake a trial: the population of interest, areas of equipoise and a plausible range of effect sizes. In WS2 (April 2024–October 2024), using an emulated target trial framework, we will attempt to make inferences about the treatment effect from such a future trial and will identify potential challenges in recruitment and estimate likely ‘intention-to-treat’ versus ‘per-protocol’ profiles; these analyses will also be useful for power calculations for future possible trials. In WS3 (October 2024–March 2025), we will convene a consensus meeting with key stakeholders, supported by a clinical trials unit, to develop a multicentre clinical trial to identify the optimal mode of birth for preterm deliveries.

Ethics and dissemination
In this study, we will use deidentified data held in the National Neonatal Research Database (NNRD), an established national population database; parents can opt out of their baby’s data being held in the NNRD. HRA/Health and Care Research Wales and National Health Service (NHS) study-specific Research Ethics Committee approval (London—Queen Square Research Ethics Committee) (Ref: 23/LO/0826) ethical approval has been obtained. Key outputs of the PRECIOUS (PREterm Caesarean/vaginal birth and IVH/OUutcomeS) study include the identification of the data, and accordingly of the multidisciplinary team required, to develop, gain funding and complete, a clinical trial to definitively identify the optimal mode of delivery for preterm infants and their mothers.

Circulation, Volume 150, Issue 10, Page 787-790, September 3, 2024.

Circulation, Ahead of Print. BACKGROUND:Empagliflozin and dapagliflozin have proven cardiovascular benefits in people with type 2 diabetes at high cardiovascular risk, but their comparative effectiveness is unknown.METHODS:This study used nationwide, population-based Danish health registries to emulate a hypothetical target trial comparing empagliflozin versus dapagliflozin initiation, in addition to standard care, among people with treated type 2 diabetes from 2014 through 2020. The outcome was a composite of myocardial infarction, ischemic stroke, heart failure (HF), or cardiovascular death (major adverse cardiovascular event). Participants were followed until an outcome, emigration, or death occurred; 6 years after initiation; or December 31, 2021, whichever occurred first. Logistic regression was used to compute inverse probability of treatment and censoring weights, controlling for 57 potential confounders. In intention-to-treat analyses, 6-year adjusted risks, risk differences, and risk ratios considering noncardiovascular death competing risks were estimated. Analyses were stratified by coexisting atherosclerotic cardiovascular disease and HF. A per-protocol design was performed as a secondary analysis.RESULTS:There were 36 670 eligible empagliflozin and 20 606 eligible dapagliflozin initiators. In the intention-to-treat analysis, the adjusted 6-year absolute risk of major adverse cardiovascular event was not different between empagliflozin and dapagliflozin initiators (10.0% versus 10.0%; risk difference, 0.0% [95% CI, −0.9% to 1.0%]; risk ratio, 1.00 [95% CI, 0.91 to 1.11]). The findings were consistent in people with atherosclerotic cardiovascular disease (risk difference, −2.3% [95% CI, −8.2% to 3.5%]; risk ratio, 0.92 [95% CI, 0.74 to 1.14]) and without atherosclerotic cardiovascular disease (risk difference, 0.3% [95% CI, −0.6% to 1.2%]; risk ratio, 1.04 [95% CI, 0.93 to 1.16]) and in people with HF (risk difference, 1.1% [95% CI, −6.5% to 8.6%]; risk ratio, 1.04 [95% CI, 0.79 to 1.37]) and without HF (risk difference, −0.1% [95% CI, −1.0% to 0.8%]; risk ratio, 0.99 [95% CI, 0.90 to 1.09]). The 6-year risks of major adverse cardiovascular event were also not different in the per-protocol analysis (9.1% versus 8.8%; risk difference, 0.2% [95% CI, −2.1% to 2.5%]; risk ratio, 1.03 [95% CI, 0.80 to 1.32]).CONCLUSIONS:Empagliflozin and dapagliflozin initiators had no differences in 6-year cardiovascular outcomes in adults with treated type 2 diabetes with or without coexisting atherosclerotic cardiovascular disease or HF.

The liver, the largest internal organ in the human body, is crucial in maintaining health and vitality. Acute liver injury (ALI) is a condition characterised by the death of hepatocytes due to necrosis and/or apoptosis. ALI can progress into a more severe and life-threatening condition known as acute liver failure (ALF). The major causes of ALI/ALF are drug-induced liver injury (DILI), viral and parasitic infections and hepatic ischaemia-reperfusion (IR) injury.1 Hepatic IR injury is a significant cause of liver injury that occurs in a variety of clinical contexts, including system shock, liver resection and liver transplantation. The underlying mechanisms of hepatic IR injury include oxygen and adenosine triphosphate (ATP) depletion, excessive inflammation, and the generation of reactive oxygen species following reperfusion. Liver transplantation is the standard treatment for end-stage liver diseases and ALF depending on the aetiology of the disease. However, the shortage of donor organs has…

Objective
Improving patient selection and development of biological therapies such as vedolizumab in IBD requires a thorough understanding of the mechanism of action and target binding, thereby providing individualised treatment strategies. We aimed to visualise the macroscopic and microscopic distribution of intravenous injected fluorescently labelled vedolizumab, vedo-800CW, and identify its target cells using fluorescence molecular imaging (FMI).

Design
Forty three FMI procedures were performed, which consisted of macroscopic in vivo assessment during endoscopy, followed by macroscopic and microscopic ex vivo imaging. In phase A, patients received an intravenous dose of 4.5 mg, 15 mg vedo-800CW or no tracer prior to endoscopy. In phase B, patients received 15 mg vedo-800CW preceded by an unlabelled (sub)therapeutic dose of vedolizumab.

Results
FMI quantification showed a dose-dependent increase in vedo-800CW fluorescence intensity in inflamed tissues, with 15 mg (153.7 au (132.3–163.7)) as the most suitable tracer dose compared with 4.5 mg (55.3 au (33.6–78.2)) (p=0.0002). Moreover, the fluorescence signal decreased by 61% when vedo-800CW was administered after a therapeutic dose of unlabelled vedolizumab, suggesting target saturation in the inflamed tissue. Fluorescence microscopy and immunostaining showed that vedolizumab penetrated the inflamed mucosa and was associated with several immune cell types, most prominently with plasma cells.

Conclusion
These results indicate the potential of FMI to determine the local distribution of drugs in the inflamed target tissue and identify drug target cells, providing new insights into targeted agents for their use in IBD.

Trial registration number
NCT04112212.

This Medical News story discusses the makeup of this fall’s updated COVID-19 vaccines.

Introduction
Gout is one of the most common forms of arthritis worldwide. Gout is particularly prevalent in Aotearoa/New Zealand and is estimated to affect 13.1% of Māori men, 22.9% of Pacific men and 7.4% of New Zealand European men. Effective long-term treatment requires lowering serum urate to