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To the Editor Dr Taccone and colleagues’ randomized clinical trial has important implications for managing critically ill patients with acute brain injury and anemia. The challenge of balancing anemia and hypoxia-related secondary brain injury against potential transfusion-related complications remains substantial.
In Reply We appreciated the opportunity to address the points raised in the thoughtful Letters regarding the TRAIN trial and its comparison with the HEMOTION trial. The difference in treatment duration between the 2 trials (ie, up to 28 days vs until ICU discharge, respectively) is indeed an important consideration. In a prior study, transfusion strategies were maintained for a maximum of 14 days, with hemoglobin values between groups tending to converge toward the end of the study period. The decision to extend the duration of transfusion thresholds in the TRAIN trial was based on the anticipated prolonged ICU stay in patients with brain injury and anemia and the hypothesis that prolonged exposure to distinct hemoglobin levels could yield a greater impact on outcomes. However, in the TRAIN study, monitoring of hemoglobin levels outside the ICU was limited to values requested by the treating physicians, potentially affecting the precision of between-group comparisons. Although the median ICU length of stay was longer in the TRAIN trial compared with the HEMOTION trial (21 vs 15 days, respectively), it remains challenging to attribute the observed differences in neurological outcomes between the 2 studies solely on this finding. Although further post hoc analyses of the TRAIN trial could help elucidate this issue, early deaths may serve as a competing risk and confound the validity of analyses related to treatment duration.
To the Editor The recently published TRAIN randomized clinical trial provided new evidence that a liberal transfusion strategy with a hemoglobin threshold of 9 g/dL significantly improved neurological outcomes at 180 days compared with a restrictive strategy with a threshold of 7 g/dL in patients with acute brain injury. Although the comparison between the TRAIN trial and the HEMOTION trial has already been well documented, we would like to highlight a previously unnoted major difference between these 2 trials, the treatment duration.
Background
Electroacupuncture (EA) is commonly used in clinical settings as a significant method for treating a variety of pain and cerebrovascular disorders. Despite its widespread use, there is limited information on the impact of perioperative EA on postoperative stroke. This study aimed to investigate whether preoperative EA therapy could reduce the occurrence of acute stroke in patients undergoing interventional surgery for intracranial aneurysms.
Methods/design
This single-centre, double-blind, placebo-controlled, randomised clinical trial aims to recruit 280 patients undergoing embolisation of intracranial aneurysms under general anaesthesia. Participants will be randomly assigned to either the EA group or sham electroacupuncture (SEA) group. The EA group will receive treatment half an hour before surgery, while the SEA group will receive sham acupuncture. The primary outcome will be the occurrence of acute stroke within 7 days post surgery. Secondary outcomes include the incidence of symptomatic and occult stroke within the same timeframe, the occurrence of cerebral vasospasm during the operation and the number of intraoperative cerebrovascular dissections.
Ethics and dissemination
This study has been approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (2023-SR-538.A1). The study started on 17 May 2024, and it is expected to end on 31 March 2025. The results of our study will be published in peer-reviewed journals.
Trial registration number
ChiCTR2300076960.
This cohort study compares kidney outcomes between initiation of empagliflozin vs dapagliflozin in adults with type 2 diabetes who were receiving antihyperglycemic treatment.
Autore/Fonte: Circulation
Objectives
To investigate the impact of allopurinol use on the risk of first-ever acute coronary syndrome (ACS) event in patients with gout.
Methods
Using national and regional register data, we included all patients with a gout diagnosis at primary or specialised care in Western Sweden in the period 2007–2017 (n=18 862; 67% male patients). Patients with a prior history of coronary heart disease (CHD) were excluded. Follow-up started at the first gout diagnosis and ended at the first-ever ACS event, death or study end. The main outcome was the risk of first-ever ACS in: (1) allopurinol users versus non-users, by defining three categories of allopurinol exposure: exposed to 100 mg, >100 mg and no exposure (reference) and (2) allopurinol initiators (within 125 days) versus long-term users (reference). Multivariable logistic regression analysis was used to calculate ORs and 95% CIs.
Results
In analysis 1 (n=18 862), 15.3% (n=2892) were exposed to 100 mg, 9.1% (n=1717) to >100 mg and 75.6% (n=14 253) were not exposed. Allopurinol users were older and had more comorbidities compared with non-users. Allopurinol exposure (100 mg and >100 mg) was associated with significantly lower odds of first-ever ACS (OR 0.77; 95% CI 0.63 to 0.94, and OR 0.61; 95% CI 0.47 to 0.81, respectively). In Analysis 2, allopurinol initiators (n=489) had significantly higher odds of first-ever ACS compared with long-term users (n=2916) (OR 1.68; 95% CI 1.03 to 2.75).
Conclusions
In patients with gout and without CHD, long-term allopurinol use protects against first-ever ACS compared with non-users. In contrast, allopurinol initiators, possibly having more systemic inflammation, had a higher risk of first-ever ACS compared with long-term users.
Stroke, Ahead of Print. BACKGROUND:Decades of experimental and clinical data revealed that spreading depolarizations (SDs) play a central causal role in the development of cortical lesions after acute brain injury. However, clinical documentation of events at the onset of focal ischemic stroke and during the initial phase of cortical injury development is lacking because electroencephalography monitoring of SD typically starts hours or days later. Here, we used nonhuman primates to map electrophysiological pathology through focal ischemic stroke’s onset and acute stage.METHODS:Craniotomies were performed over both hemispheres on 4 male and 1 female nemestrina and rhesus macaques aged 23 years to 32 years. Subdural electrode arrays were placed bilaterally over the middle cerebral artery territory, recording from 24 electrodes 1 cm apart on the left cortex and 7 on the right. After 30 minutes of baseline monitoring, the left middle cerebral artery and, in some cases, also the left internal carotid or anterior cerebral arteries were permanently occluded with aneurysmal clips.RESULTS:Repetitive SDs occurred during the next 3 hours, followed by terminal SD during euthanasia. No epileptiform activity was observed in any of the 5 animals. Nonspreading electrical silence developed in the ischemic core within seconds of ischemic onset, followed by terminal SD and SD-initiated negative ultraslow potential after several minutes. These events defined the ischemic core and led to histologically confirmed cell damage. Initial and subsequent transient SDs caused spreading depression of spontaneous activity in the normally perfused surrounding cortex without any signs of histological damage. Cardiocirculatory arrest at the end of experiments first induced nonspreading depression of activity followed by SD and, eventually, the SD-initiated negative ultraslow potential, which indicated brain death.CONCLUSIONS:Results in gyrencephalic nonhuman primates hold significant implications for understanding the role of SD in acute brain injury development and for the clinical translation and diagnosis of pathologies manifested in the SD continuum.
Circulation, Ahead of Print. Aim:The “2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes” incorporates new evidence since the “2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction” and the corresponding “2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes” and the “2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction.” The “2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes” and the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization” retire and replace, respectively, the “2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease.”Methods:A comprehensive literature search was conducted from July 2023 to April 2024. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.Structure:Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.
Objective
This study developed and validated a stacked ensemble machine learning model to predict the risk of acute kidney injury in patients with acute pancreatitis complicated by sepsis.
Design
A retrospective study based on patient data from public databases.
Participants
This study analysed 1295 patients with acute pancreatitis complicated by septicaemia from the US Intensive Care Database.
Methods
From the MIMIC database, data of patients with acute pancreatitis and sepsis were obtained to construct machine learning models, which were internally and externally validated. The Boruta algorithm was used to select variables. Then, eight machine learning algorithms were used to construct prediction models for acute kidney injury (AKI) occurrence in intensive care unit (ICU) patients. A new stacked ensemble model was developed using the Stacking ensemble method. Model evaluation was performed using area under the receiver operating characteristic curve (AUC), precision-recall (PR) curve, accuracy, recall and F1 score. The Shapley additive explanation (SHAP) method was used to explain the models.
Main outcome measures
AKI in patients with acute pancreatitis complicated by sepsis.
Results
The final study included 1295 patients with acute pancreatitis complicated by sepsis, among whom 893 cases (68.9%) developed acute kidney injury. We established eight base models, including Logit, SVM, CatBoost, RF, XGBoost, LightGBM, AdaBoost and MLP, as well as a stacked ensemble model called Multimodel. Among all models, Multimodel had an AUC value of 0.853 (95% CI: 0.792 to 0.896) in the internal validation dataset and 0.802 (95% CI: 0.732 to 0.861) in the external validation dataset. This model demonstrated the best predictive performance in terms of discrimination and clinical application.
Conclusion
The stack ensemble model developed by us achieved AUC values of 0.853 and 0.802 in internal and external validation cohorts respectively and also demonstrated excellent performance in other metrics. It serves as a reliable tool for predicting AKI in patients with acute pancreatitis complicated by sepsis.
Objective
Chronic kidney disease (CKD) is associated with a high economic burden, which is exacerbated by the high susceptibility to drug-related problems (DRPs) in this patient population. This study aimed to evaluate the cost-benefit ratio of medication reconciliation supplemented with medication review for inpatients with CKD, compared with the absence of this intervention.
Design
This was a cost-benefit analysis conducted along with a prospective interventional study.
Setting
The study was conducted at two hospitals in Jordan between February and May 2023.
Participants
The prospective interventional study included 142 admitted patients with CKD.
Interventions
Patients received medication reconciliation at admission and discharge as well as medication review throughout admission.
Primary and secondary outcome measures
The primary outcome measures were the net benefit and the benefit-to-cost ratio of the intervention. A cost-benefit analysis was conducted from the healthcare system perspective by assessing the cost of the service (the pharmacist time required to complete the service per patient) and the economic benefit, including total and per-patient cost savings and cost avoidance.
Results
The total estimated cost of all DRPs in the absence of interventions (cost avoidance) was $83 052 (average of $585±308 per patient); among which $20 623 was attributed to medication discrepancies. The cost savings were estimated at –$467. The supplemented medication reconciliation service was estimated to cost $714. As a result, the estimated net benefit totalled $81 871, averaging $577 per patient, with a benefit-to-cost ratio of 115.7:1 over the 4-month study period.
Conclusions
Delivering a supplemented medication reconciliation service by a clinical pharmacist for patients with CKD is cost beneficial from the healthcare perspective in Jordan, an example of a low- and middle-income country. This finding further confirms the pivotal role of clinical pharmacists in multidisciplinary healthcare teams.
VII Rapporto Farmacia, forti disparità regionali e generazionali
Objective
Targeted temperature management (TTM), through its physiological effects on intracranial pressure, may impede the progression to brain death (BD) in severe anoxic brain injury post-cardiac arrest (CA). We examined the potential association between the use of TTM and the occurrence of BD after CA.
Design
Monocentric, retrospective study.
Setting
Intensive care unit, Versailles Hospital, France.
Participants
Comatose survivors of CA who died from BD or postanoxic encephalopathy (PAE) after 24 hours.
Main outcome measures
PAE deaths corresponded to withdrawal of life-sustaining therapy (WLST) due to irreversible postanoxic coma or vegetative state according to prognostication guidelines. BD corresponded to the cessation of cerebral vascularisation secondary to intracranial hypertension. The diagnosis of BD was definite by clinical diagnosis of deep coma according to the Glasgow Coma Scale 3, loss of all brainstem reflexes and the demonstration of apnoea during a hypercapnia test. A cerebral omputed tomography (CT) scan or two isoelectric and unreactive electroencephalograms were used to confirm BD. To identify the independent association between TTM and BD, we conducted a multivariable logistic regression analysis.
Results
Out of 256 patients included between 2005 and 2021, 54.3% received TTM for at least 24 hours, and 56 patients (21.9%) died from BD. In the multivariable analysis, TTM for 24 hours or more was not associated with a decrease in BD (Odds Ratio 1.08, 95% CI 0.51 to 2.32). Factors associated with BD included a total duration of no-flow plus low-flow exceeding 30 min, CA due to neurological causes or hanging and a high arterial partial pressure of carbon dioxide between days 1 and 2 after admission.
Conclusions
This exploratory analysis of post-CA patients with severe anoxic brain injury did not find an association between TTM ≥24 hours and a reduction in BD. Further studies are needed to identify specific subgroups of post-CA patients for whom TTM may be especially futile or even harmful.
Yang X, He X, Pan D, et al. Intra-arterial alteplase for acute ischaemic stroke after mechanical thrombectomy (PEARL): rationale and design of a multicentre, prospective, open-label, blinded-endpoint, randomised controlled trial. BMJ Open 2024;14:e091059. doi: 10.1136/bmjopen-2024091059 This article was previously published with an error. The follow-up visit at ‘48±12 hours’ was inadvertently omitted from ‘Follow-up Procedures’ under the Methods section. To accurately reflect all key assessment points, the text has been updated to: Study visits will occur at 24±12 hours, 48±12 hours, day 7±1 or at discharge (whichever occurs first), and day 90±7. The follow-up schedule is displayed in table 1. Accordingly, table 1 has been updated to include the missing ‘48±12 hours after randomisation’ visit, during which NIHSS scores, adverse event monitoring, and concomitant medication use are documented. The missing ‘48±12 hours’ follow-up visit has also been added to the timeline in figure 2, to align with…
Stroke, Ahead of Print. BACKGROUND:Acute intermittent hypoxia (AIH) is a novel therapeutic intervention that facilitates recovery of function, but the tolerability and effectiveness have not been tested in people living with chronic stroke. The purpose here was to examine whether AIH is tolerable and effective in this population.METHODS:Ten participants with a unilateral, hemispheric stroke were assessed before and after 4 sessions of AIH separated by ≥48 hours in a case series at Shirley Ryan AbilityLab (Chicago). Physician-assessed signs and symptoms (assessed via: repeated symptom reviews, National Institutes of Health Stroke Scale, cranial nerve assessment, a muscle strength test, the Brunnstrom scale, sensory changes, reflexes, assessment of heart and lung status, Fugl-Meyer test, Chedoke-McMaster Stroke Assessment, Modified Ashworth Scale for Spasticity, and Delis Kaplan Executive Function System Color-Word Interference Test) and bilateral upper limb strength (grip and elbow flexion) were assessed before, ≈15 to 30 minutes, and ≈60 minutes after the intervention.RESULTS:AIH was well-tolerated and there were no adverse events observed. After AIH, grip strength (12.91% and 16.53% improvement at 30 and 60 minutes post-AIH, respectively) and elbow flexion force (5.87% and 7.01% improvement at 30 and 60 minutes post-AIH, respectively) improved in the more-affected limb.CONCLUSIONS:AIH is potentially safe and effective for improving strength in the more-affected limb in people living with hemiparetic stroke. Future work should explore the use of AIH to enhance task-specific training-induced plasticity.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT04019522.
This cross-sectional study explores whether hospital participation in the Acute Hospital Care at Home program continued to increase following the extension of the program and the characteristics of participating hospitals.
