Polypill Strategy in Secondary Cardiovascular Prevention.

BACKGROUND: A polypill that includes key medications associated with improved outcomes (aspirin, angiotensin-converting-enzyme [ACE] inhibitor, and statin) has been proposed as a simple approach to the secondary prevention of cardiovascular death and complications after myocardial infarction. METHODS: In this phase 3, randomized, controlled clinical trial, we assigned patients with myocardial infarction within the previous 6 months to a polypill-based strategy or usual care. The polypill treatment consisted of aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 or 40 mg). The primary composite outcome was cardiovascular death, nonfatal type 1 myocardial infarction, nonfatal ischemic stroke, or urgent revascularization. The key secondary end point was a composite of cardiovascular death, nonfatal type 1 myocardial infarction, or nonfatal ischemic stroke. RESULTS: A total of 2499 patients underwent randomization and were followed for a median of 36 months. A primary-outcome event occurred in 118 of 1237 patients (9.5%) in the polypill group and in 156 of 1229 (12.7%) in the usual-care group (hazard ratio, 0.76; 95% confidence interval [CI], 0.60 to 0.96; P = 0.02). A key secondary-outcome event occurred in 101 patients (8.2%) in the polypill group and in 144 (11.7%) in the usual-care group (hazard ratio, 0.70; 95% CI, 0.54 to 0.90; P = 0.005). The results were consistent across prespecified subgroups. Medication adherence as reported by the patients was higher in the polypill group than in the usual-care group. Adverse events were similar between groups. CONCLUSIONS: Treatment with a polypill containing aspirin, ramipril, and atorvastatin within 6 months after myocardial infarction resulted in a significantly lower risk of major adverse cardiovascular events than usual care. (Funded by the European Union Horizon 2020; SECURE ClinicalTrials.gov number, NCT02596126; EudraCT number, 2015-002868-17.).

Meningoencephalitis due to Mycobacterium lentiflavum in an immunocompromised patient: Case report.

The first case of meningoencephalitis due to Mycobacterium lentiflavum in an immunocompromised patient is reported. Clinical and radiological characteristics are described, as well as the treatment and prognosis of the patient.

Times to endovascular treatment following two triage models.

INTRODUCTION: Debate is ongoing regarding the best service model for achieving a prompt recanalization in LVO ischemic stroke with an indication for thrombectomy. We aim to assess differences between two of the existing models within our region. METHODS: We work in a cluster of three public hospitals (one hub and two spokes) forming a single functional neurology service in Madrid (Spain). Upon a LVO case out of regular hours, the interventional neuroradiologist drives to the hub hospital following the drive-the-doctor paradigm (DD). For any of the spokes, the patient is transferred to the nearest endovascular-capable hospital (drip-and-ship-DS) following the Madrid Stroke Plan. We compared times to endovascular procedures between cases managed under each model. RESULTS: Thirty-eight patients in the period April 2014-March 2021 meet the inclusion criteria (DD 27; DS 11). While baseline characteristics are comparable between groups, we observed a notable difference in the time delays favoring those managed under the DD model; with differences between median times of 105 min for hospital arrival-groin puncture (DD 140 [110-181]; DS 245 [222-310], p 0.0004); 122 min for CT-groin puncture (DD 100 [85-144]; DS 222 [200-255], p = 0.0001); and 98 min for hospital arrival-recanalization (DD 180 [140-209]; DS 278 [241-360], p = 0.0014). No differences were observed for NIHSS or mRS on discharge. CONCLUSIONS: Compared to the drip-and-ship, the drive-the-doctor triage model for patients with LVO ischemic stroke in primary centers seems to guarantee a shorter time to the start of the endovascular procedure and to recanalization in our region.

Oral anticoagulants: A plausible new treatment for Alzheimer's disease?

Alzheimer's disease (AD) and cardiovascular disease (CVD) are strongly associated. Both are multifactorial disorders with long asymptomatic phases and similar risk factors. Indeed, CVD signatures such as cerebral microbleeds, micro-infarcts, atherosclerosis, cerebral amyloid angiopathy and a procoagulant state are highly associated with AD. However, AD and CVD co-development and the molecular mechanisms underlying such associations are not understood. Here, we review the evidence regarding the vascular component of AD and clinical studies using anticoagulants that specifically evaluated the development of AD and other dementias. Most studies reported a markedly decreased incidence of composite dementia in anticoagulated patients with atrial fibrillation, with the highest benefit for direct oral anticoagulants. However, sub-analyses by differential dementia diagnosis were scarce and inconclusive. We finally discuss whether anticoagulation could be a plausible preventive/therapeutic approach for AD and, if so, which would be the best drug and strategy to maximize clinical benefit and minimize potential risks. LINKED ARTICLES: This article is part of a themed issue From Alzheimer's Disease to Vascular Dementia: Different Roads Leading to Cognitive Decline. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.6/issuetoc.

Effect of an algorithm for automatic placing of standardised test order sets on low-value appointments and attendance rates at four Spanish teaching hospitals: an interrupted time series analysis.

OBJECTIVE: Reducing backlogs for elective care is a priority for healthcare systems. We conducted an interrupted time series analysis demonstrating the effect of an algorithm for placing automatic test order sets prior to first specialist appointment on avoidable follow-up appointments and attendance rates. DESIGN: Interrupted time series analysis. SETTING: 4 academic hospitals from Madrid, Spain. PARTICIPANTS: Patients referred from primary care attending 10 033 470 outpatient appointments from 16 clinical specialties during a 6-year period (1 January 2018 to 30 June 2023). INTERVENTION: An algorithm using natural language processing was launched in May 2021. Test order sets developed for 257 presenting complaints from 16 clinical specialties were placed automatically before first specialist appointments to increase rates of diagnosis and initiation of treatment with discharge back to primary care. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes included rate of diagnosis and discharge to primary care and follow-up to first appointment index. The secondary outcome was trend in 'did not attend' rates. RESULTS: Since May 2021, a total of 1 175 814 automatic test orders have been placed. Significant changes in trend of diagnosis and discharge to primary care at first appointment (p=0.005, 95% CI 0.5 to 2.9) and 'did not attend' rates (p=0.006, 95% CI -0.1 to -0.8) and an estimated attributable reduction of 11 306 avoidable follow-up appointments per month were observed. CONCLUSION: An algorithm for placing automatic standardised test order sets can reduce low-value follow-up appointments by allowing specialists to confirm diagnoses and initiate treatment at first appointment, also leading to early discharge to primary care and a reduction in 'did not attend' rates. This initiative points to an improved process for outpatient diagnosis and treatment, delivering healthcare more effectively and efficiently.

Neutrophil ß1 adrenoceptor blockade blunts stroke-associated neuroinflammation.

BACKGROUND AND PURPOSE: Reperfusion therapy is the standard of care for ischaemic stroke; however, there is a need to identify new therapeutic targets able to ameliorate cerebral damage. Neutrophil ß1 adrenoceptors (ß1AR) have been linked to neutrophil migration during exacerbated inflammation. Given the central role of neutrophils in cerebral damage during stroke, we hypothesize that ß1AR blockade will improve stroke outcomes. EXPERIMENTAL APPROACH: Rats were subjected to middle cerebral artery occlusion-reperfusion to evaluate the effect on stroke of the selective ß1AR blocker metoprolol (12.5 mg·kg-1 ) when injected i.v. 10 min before reperfusion. KEY RESULTS: Magnetic resonance imaging and histopathology analysis showed that pre-reperfusion i.v. metoprolol reduced infarct size. This effect was accompanied by reduced cytotoxic oedema at 24 h and vasogenic oedema at 7 days. Metoprolol-treated rats showed reduced brain neutrophil infiltration and those which infiltrated displayed a high proportion of anti-inflammatory phenotype (N2, YM1+ ). Additional inflammatory models demonstrated that metoprolol specifically blocked neutrophil migration via ß1AR and excluded a significant effect on the glia compartment. Consistently, metoprolol did not protect the brain in neutrophil-depleted rats upon stroke. In patients suffering an ischaemic stroke, ß1AR blockade by metoprolol reduced circulating neutrophil-platelet co-aggregates. CONCLUSIONS AND IMPLICATIONS: Our findings describe that ß1AR blockade ameliorates cerebral damage by targeting neutrophils, identifying a novel therapeutic target to improve outcomes in patients with stroke. This therapeutic strategy is in the earliest stages of the translational pathway and should be further explored.

Missing outcome data management in acute stroke trials testing iv thrombolytics. Is there risk of bias?

INTRODUCTION: Missing outcome data may undermine interpretation of randomised clinical trials by weakening power and limiting apparent effect size. We assessed bias and inefficiency of two imputation methods commonly used in stroke trials evaluating the efficacy of iv thrombolysis. PATIENTS AND METHODS: We searched the virtual international stroke trials archive (VISTA)-acute for ischaemic stroke patients with 90-day modified Rankin scale as an outcome, and known thrombolysis status. We excluded any with missing 30-day modified Rankin scale. We planned two analyses; first, we calculated odds ratios for outcome in thrombolysed versus not thrombolysed from imputed-only data, (a) among patients with missing modified Rankin scale 90 and (b) among matched patients with intact data (using propensity score methods and relevant covariates). Imputation approaches were last observation carried forward (LOCF) or multiple imputation. Outcome comparisons used dichotomisation and shift analysis. Thereafter, we calculated whole-population odds ratios using LOCF and multiple imputation (also through dichotomisation and shift analysis); first with the original 1.5% missing outcome data, and then artificially increasing the burden (5%; 10%; 20%; 30%). RESULTS: We considered 9657 patients from eight of the studies included in VISTA, 3034 (31%) thrombolysed. Missing data replacement by LOCF with analysis by dichotomisation gave the highest estimate of thrombolysis influence. Imputing while increasing the burden of missing data progressively raised the odds ratios estimates, though thresholds for overestimation were 10% for LOCF; 20% for multiple imputation.Discussion: Replacing missing outcome data tended to overestimate differences of thrombolysed versus non-thrombolysed patients, but had minimal impact below a 10% burden of missing data.Conclusion: In the specific context of acute stroke trials testing iv thrombolytics, replacing missing data by carrying forward the last observation tended to overestimate treatment odds ratios more than multiple imputation.

Long-Term Anticoagulation in Secondary Ischemic Stroke Prevention: The Prospective Multicenter RESTAIC Registry.

Background and Objective: Oral anticoagulation (OAC) for secondary stroke prevention is recommended in atrial fibrillation (AF) and other sources of cardioembolic stroke. Our objectives were to explore the differences in ischemic and hemorrhagic events when using OAC for secondary stroke prevention according to the type of anticoagulant treatment and to analyze the number and reasons for OAC switches during long-term follow-up. Methods: Ischemic stroke (IS) patients who were discharged on OAC for secondary stroke prevention from January 2014 to October 2017 were recruited in a prospective, multicenter, hospital-based registry. Follow-up at 3 months was scheduled at the outpatient clinic with subsequent annual phone interviews for 3 years. Patients were classified into three study groups according to OAC at discharge: Vitamin K antagonist (VKA), Factor Xa inhibitor (FXa), or direct thrombin inhibitor (DTI). We compared stroke recurrences, intracranial hemorrhage, major bleeding, and all-cause mortality during the follow-up. We recorded any switches in OAC and the main reasons for the change. Results: A total of 241 patients were included. An anticoagulant was indicated in the presence of a source of cardioembolic stroke in 240 patients (99.6%) and lupus plus antiphospholipid syndrome in one patient. Up to 86 patients (35.6%) were on OAC before the index stroke; in 71 (82.5%) of them, this was VKA. At hospital discharge, 105 were treated with FXa (43.8%), 96 with VKA (39.6%), and 40 with DTI (16.6%). The cumulative incidences at 3 years were 17% for stroke recurrence, 1.6% for intracranial hemorrhage, 4.9% for major hemorrhage, and 22.8% for all-cause mortality, with no differences among the OAC groups in any outcomes. During the follow-up, 40 OAC switches were recorded (63% of them to FXa), mostly due to stroke recurrence. Conclusion: Long-term OAC in secondary stroke prevention is associated with a lower frequency of bleeding complications than stroke recurrences. No differences between anticoagulant drugs were found in any of the analyzed outcomes. The main cause for OAC switch during follow-up was stroke recurrence.

Neuroinfecciones en tiempos de COVID-19 / Neurological infections during the COVID-19 epidemic

No disponible

Neuroprotection or increased brain damage mediated by temperature in stroke is time dependent.

The control of temperature during the acute phase of stroke may be a new therapeutic target that can be applied in all stroke patients, however therapeutic window or timecourse of the temperature effect is not well established. Our aim is to study the association between changes in body temperature in the first 72 hours and outcome in patients with ischemic (IS) and hemorrhagic (ICH) stroke. We prospectively studied 2931 consecutive patients (2468 with IS and 463 with ICH). Temperature was obtained at admission, and at 24, 48 and 72 hours after admission. Temperature was categorized as low (<36°C), normal (36-37°C) and high (>37°C). As the main variable, we studied functional outcome at 3 months determined by modified Rankin Scale.Temperature in stroke patients is higher than in controls, and increases gradually in the first 72 hours after stroke. A positive correlation between temperature and stroke severity determined by NIHSS was found at 24 and 48 hours, but not at admission or 72 hours. In a logistic regression model, high temperature was associated with poor outcome at 24 hours (OR 2.05, 95% CI 1.59-2.64, p<0.0001) and 48 hours (OR 1.93, 95% CI 1.08-2.34, p = 0.007), but not at admission or 72 hours.Temperature increases in patients with stroke in the first 72 hours, with the harmful effect of high temperature occurring in the first 48 hours. The neuroprotective effect of low temperature occurs within the first 24 hours from stroke onset.

[Clopidogrel and stroke]. / Clopidogrel e ictus.

Despite the significant reduction in mortality, ischemic stroke is the leading cause of morbidity and mortality in adults in industrialized countries. Antiplatelet therapy has reduced the risk of stroke and other vascular events. Although most commonly used treatment is aspirin, other antiplatelet drugs with different mechanisms of action have been developed. Clopidogrel blocks platelet aggregation by inhibiting the adenosine diphosphate receptor and the subsequent activation of the complex IIb/IIIa. In addition to its antiplatelet action, it also has pleiotropic effects, reducing the inflammatory mechanisms that occur during ischemia. Clopidogrel has demonstrated a benefit over aspirin in preventing vascular events, especially in patients at high cardiovascular risk. In this paper we review the main studies that have been conducted with clopidogrel in preventing ischemic stroke, either as monotherapy or in combination with other antiplatelet agents.

Clopidogrel e ictus / Clopidogrel and stroke

A pesar de la importante reducción de su mortalidad, el ictus isquémico constituye la primera causa de morbimortalidad en el adulto en los países industrializados. El tratamiento antiagregante ha conseguido reducir el riesgo de ictus y otros episodios vasculares. Aunque el tratamiento más empleado es la aspirina, se han desarrollado otros antiagregantes con diferente mecanismo de acción. El clopidogrel bloquea la agregación plaquetaria al inhibir el receptor de adenosín difosfato y la subsecuente activación del complejo IIb/IIIa. Además de su poder antiagregante, también presenta efectos pleiotrópicos, disminuyendo los mecanismos inflamatorios que se producen durante la isquemia. El clopidogrel ha demostrado un beneficio con respecto a la aspirina en la prevención de episodios vasculares, sobre todo en pacientes de alto riesgo vascular. En este artículo revisamos los principales estudios que se han realizado con clopidogrel en la prevención de ictus isquémico, tanto en monoterapia como en combinación con otros antiagregantes (AU)

Despite the significant reduction in mortality, ischemic stroke is the leading cause of morbidity and mortality in adults in industrialized countries. Antiplatelet therapy has reduced the risk of stroke and other vascular events. Although ost commonly used treatment is aspirin, other antiplatelet drugs with different mechanisms of action have been developed. Clopidogrel blocks platelet aggregation by inhibiting the adenosine diphosphate receptor and the subsequent activation of the complex IIb/IIIa. In addition to its antiplatelet action, it also has pleiotropic effects, reducing the inflammatory mechanisms that occur during ischemia. Clopidogrel has demonstrated a benefit over aspirin in preventing vascular events, especially in patients at high cardiovascular risk. In this paper we review the main studies that have been conducted with clopidogrel in preventing ischemic stroke, either as monotherapy or in combination with other antiplatelet agents (AU)