Effectiveness and Safety of Antibiotics for Preventing Pneumonia and Improving Outcome after Acute Stroke: Systematic Review and Meta-analysis

Pneumonia is a common complication after stroke which increases morbidity and mortality. This systematic review was conducted to evaluate the efficacy and safety of antibiotics for the prevention of pneumonia after acute stroke. Medline, EMBASE, and Cochrane databases were searched for randomized controlled trials comparing preventive antibiotics to placebo or no antibiotics after acute stroke. The primary outcome was poststroke pneumonia. Secondary outcomes were all infections, urinary tract infections, death, dependency, length of hospital stay, and adverse events. Treatment effects were summarized using random effects metaanalysis. Six trials (4111 patients) were eligible for inclusion. The median National Institute of Health Stroke Scale score in included trials ranged from 5 to 16.5. The proportion of dysphagia ranged from 26% to 100%. Preventive antibiotics were commenced within 48 hours after acute stroke. Compared to control, preventive antibiotics reduced the risk of poststroke pneumonia (RR .75, 95%CI ·.57-.99), and all infections (RR .58, 95%CI .48-.69). There was no significant difference in the risks of dependency (RR 0.99, 95%CI 0·80-1·11), or mortality (RR .96, 95%CI .78-1.19) between the preventive antibiotics and control groups. Preventive antibiotics did not increase the risk of elevated liver enzymes (RR 1.20, 95% CI .97-1.49). Preventive antibiotics had uncertain effects on the risks of other adverse events. Preventive antibiotics reduced the risk of post-stroke pneumonia. However, there is insufficient evidence to currently recommend routine use of preventive antibiotics after acute stroke. [Abstract copyright: Copyright © 2018. Published by Elsevier Inc.

Frequency, Predictors, Management and Outcome of Post-Stroke Pneumonia

Introduction: Pneumonia is a common complication of acute stroke, occurring in up to one quarter of cases. Those who develop post-stroke pneumonia are at an increased risk of death or poor functional recovery. Despite significant advances in the treatment of stroke in the last few years uncertainty remains regarding the frequency of post-stroke pneumonia. Whether prophylactic antibiotics are effective, and the appropriateness of other management strategies to improve stroke outcomes, remains uncertain. Aims: To systematically review the evidence on post-stroke pneumonia to determine: (i) the frequency, predictors, management and outcome of post-stroke pneumonia, and (ii) whether there are effective and safe interventions to prevent pneumonia and improve the management and outcome of post-stroke pneumonia. Methods: All observational studies published before October 2017 were assessed for studies with adult patients (age ≥18 years) admitted within 30 days of acute ischaemic or haemorrhagic stroke with prospective consecutive recruitment and quantification of the proportion of people who developed pneumonia after acute stroke. Studies were included in the frequency review if they were of adult patients with acute stroke where an assessment of pneumonia was performed within 30 days of ictus (Systematic review registration: PROSPERO CRD20171221). All randomised controlled trials published before December 2016 with adult patients (age ≥18 years) admitted within 30 days of acute ischaemic or haemorrhagic stroke comparing prophylactic antibiotics for the prevention of pneumonia with placebo, no treatment or standard care were included in the management review (Systematic review registration: PROSPERO CRD42016053133). Data were identified from Medline (Medical Literature Analysis and Retrieval System Online) via Ovid, EMBASE (Excerpta Medical Database), CENTRAL (Cochrane Central Register of Controlled Trials), CINAHL (Cumulative index to nursing and allied health literature) and PsycINFO electronic databases. Results: Data were available from 47 observational studies (n=139,432 participants) and 6 trials (n=4,111 participants). The pooled frequency of post-stroke pneumonia was 12.3% (95% confidence interval [CI] 11%-13.6%, I2=98%). In pre-specified subgroup analyses, the pooled frequency of post-stroke pneumonia in 2011-2017 was 13.5% (95% CI 11.8%-15.3%, I2=98%) and this was comparable with earlier periods (P interaction=0.31). The pooled estimate of frequency of post-stroke pneumonia in the studies including only patients treated in stroke units was 7.1% (95% CI 5.8% -8.5%, I2=84%) which was significantly lower than for those treated in other locations (P interaction=0.005). The pooled frequency of post-stroke infection was 21% (95%CI 13%-29.3%; I2=99%) and of post-stroke urinary tract infection was 7.9% (95% CI 6.7%-9.3%; I2=96%). Compared to controls, preventive antibiotics reduced the risk of post-stroke pneumonia (relative risk [RR] 0·75, 95% [CI 0·57-0·99), and all infections (RR 0.58, 95%CI 0.48-0.69). There was no significant difference in the risks of dependency (RR 0.99, 95%CI 0·88-1·11), or mortality (RR 0·96, 95%CI 0·78-1·19) between the preventive antibiotic and control groups. Preventive antibiotics had uncertain effects on the risk of adverse events. Conclusions: Despite advances in the availability of acute stroke interventions, the frequency of post stroke pneumonia remains high at more than 10%. Pooled estimates indicate that the frequency of pneumonia has remained stable over recent decades. The frequency of post-stroke pneumonia is lower in patients who receive stroke unit care as compared to care in other hospital areas. While preventive antibiotics do reduce the risk of post-stroke pneumonia, uncertainty remains over whether this translates into improvements in other clinical outcomes. As such, there is insufficient evidence to recommend routine use of preventive antibiotics in the management of patients with acute stroke

Vertebrobasilar dissections: case series comparing patients with and without dissecting aneurysms

Vertebrobasilar dissections are being increasingly diagnosed due to better awareness and increased availability of modern imaging techniques of the intracranial and extracranial arteries. The clinical presentation and outcome in patients with vertebrobasilar dissections may be complicated by dissecting aneurysms. The aim of this retrospective study was to compare the clinical profile of patients with vertebrobasilar dissections with and without dissecting aneurysms, and to determine predisposing factors to the development of aneurysms. Thirty patients (19 [63%] male; median age 44.5 years) were identified. The patients were divided into two groups, an aneurysmal dissection group with seven patients and a non-aneurysmal dissection group with 23 patients. Eight (27%) patients presented with dissection after trivial trauma, three (10%) following high-speed vehicular trauma, two (7%) were associated with infection, but most (57%) were apparently spontaneous. Migraine with aura (p = 0.008) and female sex (p = 0.03) were observed more frequently in the aneurysmal dissection group. Though vascular risk factors other than hypertension and atrial fibrillation were seen in a greater percentage of patients in the non-aneurysmal dissection group, this was not statistically significant. Patients were treated with antiplatelet agents (n = 8) or warfarin (n = 13) or underwent an endovascular intervention (n = 6). Post-discharge data were available in 19 patients, of whom 14 (74%) were independent at a median follow-up of 4 months. Female sex and migraine with aura may predispose to the formation of acute dissecting aneurysms and this requires further research. Larger, prospective studies are required to ascertain epidemiologic and etiologic factors predisposing patients to the development of both intracranial and extracranial dissecting aneurysms in the vertebrobasilar circulation

Endovascular Thrombectomy for Ischemic Stroke Increases Disability-Free Survival, Quality of Life, and Life Expectancy and Reduces Cost

BackgroundEndovascular thrombectomy improves functional outcome in large vessel occlusion ischemic stroke. We examined disability, quality of life, survival and acute care costs in the EXTEND-IA trial, which used CT-perfusion imaging selection.MethodsLarge vessel ischemic stroke patients with favorable CT-perfusion were randomized to endovascular thrombectomy after alteplase versus alteplase-only. Clinical outcome was prospectively measured using 90-day modified Rankin scale (mRS). Individual patient expected survival and net difference in Disability/Quality-adjusted life years (DALY/QALY) up to 15 years from stroke were modeled using age, sex, 90-day mRS, and utility scores. Level of care within the first 90 days was prospectively measured and used to estimate procedure and inpatient care costs (US$reference year 2014).ResultsThere were 70 patients, 35 in each arm, mean age 69, median NIHSS 15 (IQR 12–19). The median (IQR) disability-weighted utility score at 90 days was 0.65 (0.00–0.91) in the alteplase-only versus 0.91 (0.65–1.00) in the endovascular group (p = 0.005). Modeled life expectancy was greater in the endovascular versus alteplase-only group (median 15.6 versus 11.2 years, p = 0.02). The endovascular thrombectomy group had fewer simulated DALYs lost over 15 years [median (IQR) 5.5 (3.2–8.7) versus 8.9 (4.7–13.8), p = 0.02] and more QALY gained [median (IQR) 9.3 (4.2–13.1) versus 4.9 (0.3–8.5), p = 0.03]. Endovascular patients spent less time in hospital [median (IQR) 5 (3–11) days versus 8 (5–14) days, p = 0.04] and rehabilitation [median (IQR) 0 (0–28) versus 27 (0–65) days, p = 0.03]. The estimated inpatient costs in the first 90 days were less in the thrombectomy group (average US$15,689 versus US$30,569, p = 0.008) offsetting the costs of interhospital transport and the thrombectomy procedure (average US$10,515). The average saving per patient treated with thrombectomy was US$4,365.ConclusionThrombectomy patients with large vessel occlusion and salvageable tissue on CT-perfusion had reduced length of stay and overall costs to 90 days. There was evidence of clinically relevant improvement in long-term survival and quality of life.Clinical Trial Registrationhttp://www.ClinicalTrials.gov NCT01492725 (registered 20/11/2011)

Healthy life-year costs of treatment speed from arrival to endovascular thrombectomy in patients with ischemic stroke

Importance The benefits of endovascular thrombectomy (EVT) are time dependent. Prior studies may have underestimated the time-benefit association because time of onset is imprecisely known. Objective To assess the lifetime outcomes associated with speed of endovascular thrombectomy in patients with acute ischemic stroke due to large-vessel occlusion (LVO). Data Sources PubMed was searched for randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time, and for which a peer-reviewed, complete primary results article was published by August 1, 2020. Study Selection All randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time were included. Data Extraction/Synthesis Patient-level data regarding presenting clinical and imaging features and functional outcomes were pooled from the 7 retrieved randomized clinical trials of stent retriever thrombectomy devices (entirely or predominantly) vs medical therapy. All 7 identified trials published in a peer-reviewed journal (by August 1, 2020) contributed data. Detailed time metrics were collected including last known well–to-door (LKWTD) time; last known well/onset-to-puncture (LKWTP) time; last known well–to-reperfusion (LKWR) time; door-to-puncture (DTP) time; and door-to-reperfusion (DTR) time. Main Outcomes and Measures Change in healthy life-years measured as disability-adjusted life-years (DALYs). DALYs were calculated as the sum of years of life lost (YLL) owing to premature mortality and years of healthy life lost because of disability (YLD). Disability weights were assigned using the utility-weighted modified Rankin Scale. Age-specific life expectancies without stroke were calculated from 2017 US National Vital Statistics. Results Among the 781 EVT-treated patients, 406 (52.0%) were early-treated (LKWTP ≤4 hours) and 375 (48.0%) were late-treated (LKWTP >4-12 hours). In early-treated patients, LKWTD was 188 minutes (interquartile range, 151.3-214.8 minutes) and DTP 105 minutes (interquartile range, 76-135 minutes). Among the 298 of 380 (78.4%) patients with substantial reperfusion, median DTR time was 145.0 minutes (interquartile range, 111.5-185.5 minutes). Care process delays were associated with worse clinical outcomes in LKW-to-intervention intervals in early-treated patients and in door-to-intervention intervals in early-treated and late-treated patients, and not associated with LKWTD intervals, eg, in early-treated patients, for each 10-minute delay, healthy life-years lost were DTP 1.8 months vs LKWTD 0.0 months; P < .001. Considering granular time increments, the amount of healthy life-time lost associated with each 1 second of delay was DTP 2.2 hours and DTR 2.4 hours. Conclusions and Relevance In this study, care delays were associated with loss of healthy life-years in patients with acute ischemic stroke treated with EVT, particularly in the postarrival time period. The finding that every 1 second of delay was associated with loss of 2.2 hours of healthy life may encourage continuous quality improvement in door-to-treatment times