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Background: India became the first country in the WHO South-East Asia Region (SEAR) to introduce the rotavirus vaccine (RVV) in the Universal immunization programme (UIP) in 2016 with nationwide expansion by 2019. It was a landmark move to reduce the diarrheal disease burden in under-five children. To assess the implementation process of introduction of RVV, Post Introduction Evaluation (PIE) was conducted in March 2022. Methods: The evaluation was conducted across 14 states, 28 districts and 28 health facilities to obtain a nationwide geographical inclusion. Stakeholders involved in program decision-making, planning, training, vaccine delivery, logistics, and communication from all levels (National, state, district, health facility, health worker, caregiver) were interviewed using standardized data collection tool for PIE (adapted from the standard WHO PIE questionnaire) and scripted on a digital tool. Results: A total of 260 interviews were conducted. Political willingness, well-planned preparedness activities, securing vaccines timely, strong supply chain monitoring, availability of domestic RVV products, quality trainings and intense communication activities were the key factors identified for the successful RVV introduction. Key activities during the introduction included cold chain space assessment, trainings of healthcare workforce, dissemination of job aids, updation of recording & reporting formats and strengthening of AEFI surveillance. Lack of community awareness for immunization in a few areas, fear of AEFI amongst some caregivers and local issues with Alternate Vaccine Delivery (AVD) were some reported challenges in achieving high coverage for RVV. Conclusions: Overall, the nationwide roll-out of RVV was smooth and the vaccine has been well-accepted in the community. The assessment emphasizes on having a well-strategized operational and communication planning, which is very crucial for any new vaccine introduction.
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BACKGROUND: With the expanding eligibility for endovascular therapy (EVT) of patients presenting in the late window (6-24 hours after last known well), we aimed to derive a score to predict favorable outcomes associated with EVT versus best medical management. METHODS AND RESULTS: A multinational observational cohort of patients from the CLEAR (Computed Tomography for Late Endovascular Reperfusion) study with proximal intracranial occlusion (2014-2022) was queried (n=58 sites). Logistic regression analyses were used to derive a 9-point score for predicting good functional outcome (modified Rankin Scale score 0-2 or return to premorbid modified Rankin Scale score) at 90 days, with sensitivity analyses for prespecified subgroups conducted using bootstrapped random forest regressions. Secondary outcomes included 90-day functional independence (modified Rankin Scale score 0-2), poor outcome (modified Rankin Scale score 5-6), and 90-day survival. The score was externally validated with a single-center cohort (2014-2023). Of the 3231 included patients (n=2499 EVT), a 9-point score included age, early computed tomography ischemic changes, and stroke severity, with higher points indicating a higher probability of a good functional outcome. The areas under the curve for the primary outcome among EVT and best medical management subgroups were 0.72 (95% CI, 0.70-0.74) and 0.87 (95% CI, 0.84-0.90), respectively, with similar performance in the external validation cohort (area under the curve, 0.71 [95% CI, 0.66-0.76]). There was a significant interaction between the score and EVT for good functional outcome, functional independence, and poor outcome (all Pinteraction<0.001), with greater benefit favoring patients with lower and midrange scores. CONCLUSIONS: This score is a pragmatic tool that can estimate the probability of a good outcome with EVT in the late window. REGISTRATION: URL: https://www.Clinicaltrials.gov; Unique identifier: NCT04096248.
Subject(s)
Endovascular Procedures , Thrombectomy , Humans , Male , Female , Endovascular Procedures/methods , Aged , Thrombectomy/methods , Middle Aged , Treatment Outcome , Time Factors , Ischemic Stroke/physiopathology , Ischemic Stroke/therapy , Recovery of Function , Functional Status , Predictive Value of Tests , Risk Assessment/methods , Time-to-Treatment , Tomography, X-Ray ComputedABSTRACT
Background and aims: The Rotavirus vaccine (RVV) introduction is a landmark event in the history of Indian public health as for the first time a novel, low-cost indigenous vaccine was introduced in a short timeline between 2016 and 2019. As per WHO mandate, post-introduction evaluation (PIE) be conducted within 6 to 12 months of vaccine introduction to provide an understanding of the operational aspects of the program. For RVV PIE, an innovative approach to developing and deploying a digitized tool was employed. The present study aims to document the processes followed for digitizing the data collection and analysis tools. Methods: The development of the RVV-PIE digital tool was undertaken in two phases. In the first phase, conceptualization and iteration of the modified WHO PIE tool were undertaken. Questions were organized sequentially to ensure natural progression in responses. The finalized questionnaire was converted to a digital version and extensive dummy data was entered to improve automated qualitative data analysis. Phase 2 involved updating the draft tool and incorporating changes to provide a field-tested version for deployment. Results: The digital version of the tool was successfully developed. The GPS functionality of the tool allowed live tracking of data collection making the process more accountable. The tool was prepopulated with reference materials and data points for easy reference and retrieval by the evaluators. The digitization of the tool also allowed easy visualization of data through maps, charts, and graphs on a real-time user-friendly dashboard. Conclusions: The digitization of the PIE tool for RVV in India has been a great learning experience where the dire situation of an ongoing pandemic catapulted us towards a more efficient and comprehensive process innovation. The RVV PIE tool could serve as a customizable digital PIE tool for other health programs heralding an era of a more effective and proficient process of PIE.
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BACKGROUND: Tandem lesions consist of cervical internal carotid artery (ICA) stenosis or occlusion, most commonly of atherosclerosis or dissection etiology, plus a large vessel occlusion. In this study, we compare outcomes in patients with atherosclerosis versus dissection of the cervical ICA. METHODS: This multicenter retrospective cohort study includes data from tandem lesion patients who underwent endovascular treatment from 2015 to 2020. Atherosclerosis was defined as ICA stenosis/occlusion associated with a calcified lesion and dissection by the presence of a tapered or flame-shaped lesion and intramural hematoma. Primary outcome: 90-day functional independence (modified Rankin Scale score, 0-2); secondary outcomes: 90-day favorable shift in the modified Rankin Scale score, modified Thrombolysis in Cerebral Infarction score 2b-3, modified Thrombolysis in Cerebral Infarction score 2c-3, symptomatic intracranial hemorrhage, parenchymal hematoma type 2, petechial hemorrhage, distal embolization, early neurological improvement, and mortality. Analysis was performed with matching by inverse probability of treatment weighting. RESULTS: We included 526 patients (68 [59-76] years; 31% females); 11.2% presented dissection and 88.8%, atherosclerosis. Patients with dissection were younger, had lower rates of hypertension, hyperlipidemia, diabetes, and smoking history. They also exhibited higher rates of ICA occlusion, multiple stents (>1), and lower rates of carotid self-expanding stents. After matching and adjusting for covariates, there were no differences in 90-day functional independence. The rate of successful recanalization was significantly lower in the dissection group (adjusted odds ratio, 0.38 [95% CI, 0.16-0.91]; P=0.031), which also had significantly higher rates of distal emboli (adjusted odds ratio, 2.53 [95% CI, 1.15-5.55]; P=0.021). There were no differences in other outcomes. Acute ICA stenting seemed to increase the effect of atherosclerosis in successful recanalization. CONCLUSIONS: This study reveals that among patients with acute stroke with tandem lesions, cervical ICA dissection is associated with higher rates of distal embolism and lower rates of successful recanalization than atherosclerotic lesions. Using techniques to minimize the risk of distal embolism may mitigate this contrast. Further prospective randomized trials are warranted to fully understand these associations.
Subject(s)
Endovascular Procedures , Humans , Female , Middle Aged , Male , Aged , Retrospective Studies , Endovascular Procedures/methods , Carotid Artery, Internal, Dissection/diagnostic imaging , Carotid Artery, Internal, Dissection/surgery , Carotid Artery, Internal, Dissection/therapy , Carotid Stenosis/surgery , Carotid Stenosis/complications , Treatment Outcome , EmbolismABSTRACT
BACKGROUND: Studies comparing bridging intravenous thrombolysis (IVT) with direct endovascular therapy (EVT) in patients with acute ischemic stroke who present late are limited. We aimed to compare the clinical outcomes and safety of bridging IVT in patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent EVT 6 to 24 hours after time last known well. METHODS: We enrolled patients with anterior circulation large vessel occlusion stroke and a National Institutes of Health Stroke Scale score of ≥6 from 20 centers across 10 countries in the multicenter retrospective CLEAR study (CT for Late Endovascular Reperfusion) between January 2014 and May 2022. We used inverse probability of treatment weighting modeling adjusted for clinical and imaging confounders to compare functional outcomes, reperfusion success, symptomatic intracranial hemorrhage, and mortality between EVT patients with and without prior IVT. RESULTS: Of 5098 patients screened for eligibility, we included 2749 patients, of whom 549 received bridging IVT before EVT. The timing of IVT was not recorded. Witnessed stroke onset and transfer rates were higher in the bridging IVT group (25% versus 12% and 77% versus 55%, respectively, P value for both <0.0001), and time intervals between stroke onset and treatment were shorter (time last known well-start of EVT median 560 minutes [interquartile range, 432-791] versus 724 minutes [interquartile range, 544-912]; P<0.0001). After adjustment for confounders, there was no difference in functional outcome at 3 months (adjusted common odds ratio for modified Rankin Scale shift, 1.03 [95% CI, 0.89-1.19]; P=0.72) or successful reperfusion (adjusted odds ratio, 1.19 [95% CI, 0.81-1.75]; P=0.39). There were no safety concerns associated with bridging IVT versus direct EVT (symptomatic intracranial hemorrhage: adjusted odds ratio, 0.75 [95% CI, 0.38-1.48]; P=0.40; mortality: adjusted odds ratio, 1.14 [95% CI, 0.89-1.46]; P=0.31). Results were unchanged when the analysis was limited to patients who received IVT >6 hours after last known well. CONCLUSIONS: In patients with an anterior circulation large vessel occlusion stroke who underwent EVT 6 to 24 hours from last known well, bridging IVT was not associated with a difference in outcomes compared with direct EVT. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096248.
Subject(s)
Endovascular Procedures , Ischemic Stroke , Thrombolytic Therapy , Humans , Male , Female , Aged , Ischemic Stroke/therapy , Ischemic Stroke/drug therapy , Ischemic Stroke/surgery , Endovascular Procedures/methods , Middle Aged , Thrombolytic Therapy/methods , Treatment Outcome , Retrospective Studies , Aged, 80 and over , Fibrinolytic Agents/therapeutic use , Fibrinolytic Agents/administration & dosage , Time-to-Treatment , Brain Ischemia/drug therapy , Brain Ischemia/therapyABSTRACT
BACKGROUND AND OBJECTIVES: There is uncertainty whether patients with large vessel occlusion (LVO) presenting in the late 6-hour to 24-hour time window can be selected for endovascular therapy (EVT) by noncontrast CT (NCCT) and CT angiography (CTA) for LVO detection. We evaluated the clinical outcomes of patients selected for EVT by NCCT compared with those medically managed in the extended time window. METHODS: This multinational cohort study was conducted at 66 sites across 10 countries. Consecutive patients with proximal anterior LVO stroke selected for EVT by NCCT or medically managed and presenting within 6-24 hours of time last seen well (TSLW) from January 2014 to May 2022 were included. The primary end point was the 90-day ordinal shift in the modified Rankin Scale (mRS) score. Inverse probability treatment weighting (IPTW) and multivariable methods were used. RESULTS: Of 5,098 patients screened, 839 patients were included, with a median (interquartile range) age of 75 (64-83) years; 455 (54.2%) were women. There were 616 patients selected to undergo EVT by NCCT (73.4%) and 223 (26.6%) who were medically managed. In IPTW analyses, there was a more favorable 90-day ordinal mRS shift in patients selected by NCCT to EVT vs those who were medically managed (odds ratio [OR] 1.99, 95% CI 1.53-2.59; p < 0.001). There were higher rates of 90-day functional independence (mRS 0-2) in the EVT group (40.1% vs 18.4%, OR 3.31, 95% CI 2.11-5.20; p < 0.001). sICH was nonsignificantly higher in the EVT group (8.5% vs 1.4%, OR 3.77, 95% CI 0.72-19.7, p = 0.12). Mortality at 90 days was lower in the EVT vs MM group (23.9% vs 32.3%, OR 0.61, 95% CI 0.45-0.83, p = 0.002). DISCUSSION: In patients with proximal anterior LVO in the extended time window, there was a lower rate of disability and mortality in patients selected with NCCT and CTA to EVT compared with those who were medically managed. These findings support the use of NCCT as a simpler and more inclusive approach to patient selection in the extended window. TRIAL REGISTRATION INFORMATION: This study was registered at ClinicalTrials.gov under NCT04096248. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with proximal anterior circulation occlusion presenting with ischemic stroke from 6 to 24 hours, compared with medical management, those undergoing thrombectomy based on NCCT have reduced disability and mortality at 90 days.
Subject(s)
Endovascular Procedures , Thrombectomy , Humans , Female , Aged , Male , Thrombectomy/methods , Aged, 80 and over , Middle Aged , Endovascular Procedures/methods , Computed Tomography Angiography , Tomography, X-Ray Computed , Cohort Studies , Time-to-Treatment , Treatment Outcome , Cerebral AngiographyABSTRACT
Background: Estimates suggest that 78,000 children died due to rotavirus gastroenteritis annually between 2011 and 2013 in India. The north eastern state of Assam reported 38.4% pediatric diarrheal admissions testing positive for rotavirus. Rotavirus vaccine (RVV) was introduced in Assam in 2017 following which the National Family Health Survey-5 (NFHS-5) (2019) revealed low RVV coverage in Assam with wide variation between the districts. the current study was conceptualized and undertaken to capture the enablers and barriers to RVV coverage in Assam. Methods: Qualitative study conducted in 5 randomly selected districts in Assam. Participants (key informants) were recruited by purposive sampling at each level of the health system including healthcare officials, service providers and caregivers based on availability. Thirty-five in-depth interviews (IDIs) and five focus group discussions (FGDs) were conducted. Interviews were tape recorded and transcribed. Data was coded and analyzed using the thematic framework approach. Results: Findings from the qualitative data collection were collated and analyzed under 7 identified themes. Difficult terrain, limited service provider availability and no catch-up training for new recruits were some of the barriers to RVV coverage. In contrast, Information, Education & Communication (IEC) in vernacular language, RVV safety profile, development partner support and adequate RVV supply were identified as some of the enablers of RVV coverage. Conclusion: Few broad recommendations to overcome identified barriers include comprehensive inter-sectoral coordination, regular monitoring and frequent refresher training sessions. There is a need for a future study utilizing existing coverage data and larger sample size to triangulate the findings of this study.
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BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder affecting the skinfold regions. There is growing appreciation of the need for socioeconomic factors to be included in multidisciplinary assessments of HS. However, knowledge regarding HS and workplace function is limited. OBJECTIVES: To assess the relationship between HS and workplace function. METHODS: Cinahl, Embase, MedLine, PsycInfo and PubMed were systematically searched to collect data from studies in which validated surveys of workplace function were administered to HS patients. RESULTS: Out of 1,932 publications, twelve studies were included in this review and seven reported sufficient data for meta-analysis. Included studies encompassed 5,187 HS patients and no controls. All studies employed the Work Productivity and Activity Impairment questionnaire, reporting percentage scores for absenteeism, presenteeism, total work productivity impairment (TWPI) and total activity impairment (TAI). Pooled mean scores for HS were calculated as 10.17% (95%CI 8.68-11.66) for absenteeism, 31.13% (95%CI 25.02-37.23) for presenteeism, 34.25% (95%CI 29.37-39.14) for TWPI, and 42.23% (95%CI 38.56-45.89) for TAI. Significant heterogeneity was identified and most studies were of 'poor' to 'fair' quality. CONCLUSIONS: Current evidence suggests considerable impairment of workplace functioning in HS patients. Our findings point to a significant unmet treatment need with respect to improving working capability in HS. The extant literature is inadequate to reliably assess the mechanisms underlying this effect or to comparatively assess the capabilities of HS therapies to improve workplace function.
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Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are essentially different manifestations of the same disease that are similarly managed. A number of molecular and cytogenetic variables with prognostic implications have been identified. Undetectable minimal residual disease at the end of treatment with chemoimmunotherapy or venetoclax-based combination regimens is an independent predictor of improved survival among patients with previously untreated or relapsed/refractory CLL/SLL. The selection of treatment is based on the disease stage, presence or absence of del(17p) or TP53 mutation, immunoglobulin heavy chain variable region mutation status, patient age, performance status, comorbid conditions, and the agent's toxicity profile. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with CLL/SLL.
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Leukemia, Lymphocytic, Chronic, B-Cell , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Prognosis , ImmunotherapyABSTRACT
BACKGROUND AND AIMS: There is no clear consensus on ideal systolic blood pressure (SBP) target post-endovascular thrombectomy (EVT) in patients with acute ischemic stroke. This study intends to investigate the relationship between reducing SBP and clinical outcomes and to determine the therapeutic efficacy of moderate and intensive SBP reduction post EVT. METHODS: A comprehensive search was conducted across five electronic databases to identify studies relevant to our analysis. Data from these studies were then analyzed using pooled relative risk (RR) along with their corresponding 95 % confidence intervals (CI) for our categorical outcomes. functional independence at 90 days post-EVT was defined as a modified Rankin score (mRS) 0-2. RESULTS: Our meta-analysis included eight studies with 2922 patients: 1376 patients were treated with intensive SBP reduction, 306 with moderate SBP reduction, and 1243 with standard SBP reduction. There was no difference in the risk of functional independence at 90 days post-EVT with both intensive-SBP reduction (target 120-140 mmHg, relative risk (RR) =1.05, 95 % CI 0.82, 1.34, p = 0.72) and moderate-SBP reduction (>160 mm Hg) (RR= 0.95, 95 % CI 0.69, 1.31, p = 0.76) compared with standard SBP reduction (>180 mm Hg). The risk of symptomatic intracranial hemorrhage (sICH) did not significantly differ between standard-SBP reduction and intensive-SBP reduction (RR = 0.93, 95 % CI 0.66, 1.31, p = 0.36) or moderate-SBP reduction (0.72 (95 % CI [0.28, 1.87], p = 0.50) groups, respectively. Intensive-SBP reduction significantly decreased the risk of hemicraniectomy. CONCLUSIONS: We did not identify any difference in functional independence at 90 days in acute ischemic stroke patients with either intensive-SBP reduction or moderate-SBP reduction compared with standard SBP reduction post-EVT.
Subject(s)
Blood Pressure , Endovascular Procedures , Ischemic Stroke , Recovery of Function , Thrombectomy , Humans , Thrombectomy/adverse effects , Endovascular Procedures/adverse effects , Ischemic Stroke/physiopathology , Ischemic Stroke/diagnosis , Ischemic Stroke/therapy , Ischemic Stroke/etiology , Treatment Outcome , Risk Factors , Aged , Time Factors , Male , Female , Middle Aged , Functional Status , Antihypertensive Agents/therapeutic use , Disability Evaluation , Aged, 80 and overABSTRACT
BACKGROUND: Quality measures determine reimbursement rates and penalties in value-based payment models. Frailty impacts these quality metrics across surgical specialties. We compared the discriminatory thresholds for the risk analysis index (RAI), modified frailty index-5 (mFI-5) and increasing patient age for the outcomes of extended length of stay (LOS [eLOS]), prolonged LOS within 30 days (pLOS), and protracted LOS (LOS > 30). METHODS: Patients ≥18 years old who underwent neurosurgical procedures between 2012 and 2020 were queried from the ACS-NSQIP. We performed receiver operating characteristic analysis, and multivariable analyses to examine discriminatory thresholds and identify independent associations. RESULTS: There were 411,605 patients included, with a median age of 59 years (IQR, 48-69), 52.2% male patients, and a white majority 75.2%. For eLOS: RAI C-statistic 0.653 (95% CI: 0.652-0.655), versus mFI-5 C-statistic 0.552 (95% CI: 0.550-0.554) and increasing patient age C-statistic 0.573 (95% CI: 0.571-0.575). Similar trends were observed for pLOS- RAI: 0.718, mFI-5: 0.568, increasing patient age: 0.559, and for LOS>30- RAI: 0.714, mFI-5: 0.548, and increasing patient age: 0.506. Patients with major complications had eLOS 10.1%, pLOS 26.5%, and LOS >30 45.5%. RAI showed a larger effect for all three outcomes, and major complications in multivariable analyses. CONCLUSION: Increasing frailty was associated with three key quality metrics that is, eLOS, pLOS, LOS > 30 after neurosurgical procedures. The RAI demonstrated a higher discriminating threshold compared to both mFI-5 and increasing patient age. Preoperative frailty screening may improve quality metrics through risk mitigation strategies and better preoperative communication with patients and their families.
Subject(s)
Frailty , Length of Stay , Neurosurgical Procedures , Humans , Middle Aged , Male , Female , Frailty/diagnosis , Aged , Length of Stay/statistics & numerical data , Risk Assessment , Neurosurgical Procedures/statistics & numerical data , Quality Indicators, Health Care , Retrospective Studies , Adult , Age FactorsABSTRACT
While most friction burns are adequately managed in an outpatient setting, many may require hospital admission, operative excision, and extended care. To this day, there is a wide variance in friction burn management. Our goal is to review the etiology, management, and outcomes of such burns warranting hospitalization. We conducted a retrospective review of all friction burns admitted to a single, American Burn Association-verified burn center from January 1, 2016 to December 31, 2020. A total of 28 (34%) patients required surgery for their friction burns and 15 (18%) ultimately required a split-thickness skin graft. The mean number of operations was 2.4 (95% CI 1.6-3.1). Overall, the operative group was younger (29.9 vs 38.3 years, P = .026), more likely to have a concomitant traumatic brain injury (25% vs 7%, P = .027), and had a longer hospital length of stay (17.5 vs 3.9 days, P < .001). Both groups had a similar overall TBSA (8.5% vs 10.0%, P = .35), but the operative group had a larger surface area comprised of third-degree burns (3.05% vs 0.2%, P < .001). Overall, friction burns resulting in hospital admission are associated with high-energy traumatic mechanisms and concomitant injuries. Patients who need operative intervention for their burns typically require multiple procedures often culminating in a split-thickness skin graft. While non-operative management of friction burns with topical agents has been found to be successful, patients with higher injury severity scores should be monitored very closely as they may require surgical excision.
Subject(s)
Burns , Friction , Skin Transplantation , Humans , Burns/therapy , Male , Retrospective Studies , Adult , Female , Length of Stay/statistics & numerical data , Patient Discharge , Burn Units , Middle Aged , HospitalizationABSTRACT
BACKGROUND: Endovascular therapy (EVT) stands as an established and effective intervention for acute ischemic stroke in patients harboring tandem lesions (TLs). However, the optimal anesthetic strategy for EVT in TL patients remains unclear. This study aims to evaluate the impact of distinct anesthetic techniques on outcomes in acute ischemic stroke patients presenting with TLs. METHODS: Patient-level data, encompassing cases from 16 diverse centers, were aggregated for individuals with anterior circulation TLs treated between January 2015 and December 2020. A stratification based on anesthetic technique was conducted to distinguish between general anesthesia (GA) and procedural sedation (PS). Multivariable logistic regression models were built to discern the association between anesthetic approach and outcomes, including the favorable functional outcome defined as 90-day modified Rankin Score (mRS) of 0-2, ordinal shift in mRS, symptomatic intracranial hemorrhage (sICH), any hemorrhage, successful recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) score ≥2b), excellent recanalization (mTICI 3), first pass effect (FPE), early neurological improvement (ENI), door-to-groin and recanalization times, intrahospital mortality, and 90-day mortality. RESULTS: Among 691 patients from 16 centers, 595 patients (GA 38.7%, PS 61.3%) were included in the final analysis. There were no significant differences noted in the door-to-groin time (80 (46-117.5) mins vs 54 (21-100), P=0.607) and groin to recanalization time (59 (39.5-85.5) mins vs 54 (38-81), P=0.836) among the groups. The odds of a favorable functional outcome (36.6% vs 52.6%; adjusted OR (aOR) 0.56, 95% CI 0.38 to 0.84, P=0.005) and a favorable shift in the 90-day mRS (aOR 0.71, 95% CI 0.51 to 0.99, P=0.041) were lower in the GA group. No differences were noted for sICH (3.9% vs 4.7%, P=0.38), successful recanalization (89.1% vs 86.5%, P=0.13), excellent recanalization (48.5% vs 50.3%, P=0.462), FPE (53.6% vs 63.4%, P=0.05), ENI (38.9% vs 38.8%, P=0.138), and 90-day mortality (20.3% vs 16.3%, P=0.525). An interaction was noted for favorable functional outcome between the type of anesthesia and the baseline Alberta Stroke Program Early CT Score (ASPECTS) (P=0.033), degree of internal carotid artery (ICA) stenosis (P<0.001), and ICA stenting (P<0.001), and intraparenchymal hematoma between the type of anesthesia and intravenous thrombolysis (P=0.019). In a subgroup analysis, PS showed better functional outcomes in patients with age ≤70 years, National Institutes of Health Stroke Scale (NIHSS) score <15, and acute ICA stenting. CONCLUSIONS: Our findings suggest that the preference for PS not only aligns with comparable procedural safety but is also associated with superior functional outcomes. These results prompt a re-evaluation of current anesthesia practices in EVT, urging clinicians to consider patient-specific characteristics when determining the optimal anesthetic strategy for this patient population.
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BACKGROUND: Thrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.5 hours is limited. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well. Patients had to have evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging. The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death) at day 90. Safety outcomes included death and symptomatic intracranial hemorrhage. RESULTS: The trial enrolled 458 patients, 77.3% of whom subsequently underwent thrombectomy; 228 patients were assigned to receive tenecteplase, and 230 to receive placebo. The median time between the time the patient was last known to be well and randomization was approximately 12 hours in the tenecteplase group and approximately 13 hours in the placebo group. The median score on the modified Rankin scale at 90 days was 3 in each group. The adjusted common odds ratio for the distribution of scores on the modified Rankin scale at 90 days for tenecteplase as compared with placebo was 1.13 (95% confidence interval, 0.82 to 1.57; P = 0.45). In the safety population, mortality at 90 days was 19.7% in the tenecteplase group and 18.2% in the placebo group, and the incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively. CONCLUSIONS: Tenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by Genentech; TIMELESS ClinicalTrials.gov number, NCT03785678.).
Subject(s)
Brain Ischemia , Ischemic Stroke , Perfusion Imaging , Tenecteplase , Thrombectomy , Tissue Plasminogen Activator , Humans , Brain Ischemia/diagnostic imaging , Brain Ischemia/drug therapy , Brain Ischemia/mortality , Brain Ischemia/surgery , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/adverse effects , Fibrinolytic Agents/therapeutic use , Intracranial Hemorrhages/chemically induced , Intracranial Hemorrhages/diagnostic imaging , Perfusion , Perfusion Imaging/methods , Stroke/diagnostic imaging , Stroke/drug therapy , Stroke/mortality , Stroke/surgery , Tenecteplase/administration & dosage , Tenecteplase/adverse effects , Tenecteplase/therapeutic use , Thrombectomy/adverse effects , Thrombectomy/methods , Tissue Plasminogen Activator/administration & dosage , Tissue Plasminogen Activator/adverse effects , Tissue Plasminogen Activator/therapeutic use , Treatment Outcome , Double-Blind Method , Ischemic Stroke/diagnostic imaging , Ischemic Stroke/drug therapy , Ischemic Stroke/mortality , Ischemic Stroke/surgery , Infarction, Middle Cerebral Artery/diagnostic imaging , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/surgery , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/drug therapy , Carotid Artery Diseases/surgery , Brain/blood supply , Brain/diagnostic imaging , Time-to-TreatmentABSTRACT
The doping of engineered nanomaterials (ENMs) is a key tool for manipulating the properties of ENMs (e.g., electromagnetic, optical, etc.) for different therapeutic applications. However, adverse health outcomes and the cellular biointeraction of doped ENMs, compared to undoped counterparts, are not fully understood. Previously, we have shown that doping manganese oxide nanoparticles with ZnO (ZnO-MnO2 NPs) improved their catalytic properties. In this study, we assessed the toxicity of ZnO-MnO2 NPs in Raw 264.7 cells. NPs were prepared via an eco-friendly, co-precipitation method and characterized by several techniques, including transmission and scanning electron microscopy, X-ray diffraction, and Fourier transform infrared. The physicochemical properties of ZnO-MnO2 NPs, including size, morphology, and crystalline structure, were almost identical to MnO2 NPs. However, ZnO-MnO2 NPs showed slightly larger particle aggregates and negative charge in cell culture media. Exposure to ZnO-MnO2 NPs resulted in lower toxicity based on the cell viability and functional assay (phagocytosis) data. Exposure to both NPs resulted in the activation of the cell inflammatory response and the generation of reactive oxygen species (ROS). Despite this, exposure to ZnO-MnO2 NPs was associated with a lower toxicity profile, and it resulted in a higher ROS burst and the activation of the cell antioxidant system, hence indicating that MnO2 NP-induced toxicity is potentially mediated via other ROS-independent pathways. Furthermore, the cellular internalization of ZnO-MnO2 NPs was lower compared to MnO2 NPs, and this could explain the lower extent of toxicity of ZnO-MnO2 NPs and suggests Zn-driven ROS generation. Together, the findings of this report suggest that ZnO (1%) doping impacts cellular biointeraction and the consequent toxicological outcomes of MnO2 NPs in Raw 264.7 cells.
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BACKGROUND: Racial and ethnic disparities have been observed in the multidisciplinary management of pancreatic ductal adenocarcinoma. Intraductal papillary mucinous neoplasm is the most common identifiable precursor to pancreatic ductal adenocarcinoma, where early surgical intervention before the development of an invasive intraductal papillary mucinous neoplasm improves survival. The association of race/ethnicity with the risk of identifying invasive intraductal papillary mucinous neoplasms during resection has not been previously defined. METHODS: The American College of Surgeons National Quality Improvement Program targeted pancreatectomy database (2014-2021) was queried for patients with race/ethnicity data who underwent resection of an intraductal papillary mucinous neoplasm. Backward Wald logistic regression modeling (P ≤ 0.05 for entry; P > .10 for removal) was used to identify independent predictors of invasion. RESULTS: A total of 4,505 cases of resected intraductal papillary mucinous neoplasms were identified, with 923 (20.5%) demonstrating invasive intraductal papillary mucinous neoplasms. The cohort of individuals other than non-Hispanic Whites were significantly more likely to have invasive intraductal papillary mucinous neoplasms (White, 19.9%; Black, 24.2%; Asian, 23.7%; Hispanic, 22.6%; P = .026). Such disparity could not be explained by greater comorbidity, as non-White patients were significantly younger (age <65 years: 41.7% vs 33.2%, P < .001) and had better physical status (American Society of Anesthesiologists score ≤2: 28.8% vs 25.2%, P = .053). After controlling for clinicodemographic variables, being an individual of race/ethnicity other than White was independently associated with higher odds of invasive intraductal papillary mucinous neoplasms (odds ratio, 1.280; 95% confidence interval, 1.046-1.566; P = .017). No differences in postoperative morbidity were observed. CONCLUSION: In a national cohort of patients with resected intraductal papillary mucinous neoplasms, individuals who identified as being of race/ethnicity other than White were significantly more likely to have invasive intraductal papillary mucinous neoplasms during surgical resection.
Subject(s)
Carcinoma, Pancreatic Ductal , Neoplasms, Cystic, Mucinous, and Serous , Pancreatic Neoplasms , Humans , United States/epidemiology , Aged , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/pathology , Pancreatectomy , Pancreatic Ducts/surgery , Neoplasms, Cystic, Mucinous, and Serous/surgery , Neoplasm Invasiveness , Retrospective StudiesABSTRACT
Scimitar syndrome is a rare congenital cardiopulmonary anomaly; it is also called venolobar syndrome, hypogenic lung syndrome, and Halasz syndrome. The syndrome is characterized by cardiac dextroposition, right lung and pulmonary artery hypoplasia as well as complete or partial anomalous pulmonary venous drainage of the right lung. We report a case of a 22-month-old full-term male child with a severe form of scimitar syndrome diagnosed at birth. The X-ray demonstrated dextrocardia and right lung hypoplasia, while the echocardiography clearly illustrated the scimitar vein. The patient had multiple ER visits and hospitalizations due to asthma exacerbation that was aggravated by recurrent respiratory tract infections; he responded well to asthma medications during his admissions yet compliance to his prophylactic asthma medications was poor at home.
ABSTRACT
BACKGROUND: The association between sex and outcome after endovascular thrombectomy of acute ischemic stroke is unclear. The aim of this study was to compare the clinical and safety outcomes between men and women treated with endovascular thrombectomy in the late 6-to-24-hour window period. METHODS: This multicenter, retrospective observational cohort study included consecutive patients who underwent endovascular thrombectomy of anterior circulation stroke in the late window from 66 clinical sites in 10 countries from January 2014 to May 2022. The primary outcome was the 90-day ordinal modified Rankin Scale score. Secondary outcomes included 90-day functional independence (FI), return of Rankin (RoR) to prestroke baseline, FI or RoR, symptomatic intracranial hemorrhage, and mortality. Multivariable and inverse probability of treatment weighting methods were used. We explored the interaction of sex with baseline characteristics on the outcomes ordinal modified Rankin Scale and FI or RoR. RESULTS: Of 1932 patients, 1055 were women and 877 were men. Women were older (77 versus 69 years), had higher rates of atrial fibrillation, hypertension, and greater prestroke disability, but there was no difference in baseline National Institutes of Health Stroke Scale score. Inverse probability of treatment weighting analysis showed no difference between women and men in ordinal modified Rankin Scale (odds ratio, 0.98 [95% CI, 0.79-1.21]), FI or RoR (odds ratio, 0.98 [95% CI, 0.78-1.22]), severe disability or mortality (odds ratio, 0.99 [95% CI, 0.80-1.23]). The multivariable analysis of the above end points was concordant. There were no interactions between baseline characteristics and sex on the outcomes of ordinal modified Rankin Scale and FI or RoR. CONCLUSIONS: In late presenting patients with anterior circulation stroke treated with endovascular thrombectomy in the 6 to 24-hour window, there was no difference in clinical or safety outcomes between men and women.
Subject(s)
Atrial Fibrillation , Ischemic Stroke , Stroke , United States , Humans , Female , Male , Sex Characteristics , Retrospective Studies , Stroke/surgerySubject(s)
Adenine , Benzamides , Piperidines , Pyrazines , Pyrazoles , Pyrimidines , Humans , Piperidines/therapeutic use , Adenine/analogs & derivatives , Benzamides/therapeutic use , Pyrimidines/adverse effects , Pyrimidines/therapeutic use , Pyrimidines/administration & dosage , Pyrazoles/therapeutic use , Pyrazoles/adverse effects , Pyrazoles/administration & dosage , Pyrazines/therapeutic use , Pyrazines/adverse effects , Pyrazines/administration & dosage , Sulfonamides/therapeutic use , Sulfonamides/adverse effects , Aminobutyrates/therapeutic use , Aminobutyrates/adverse effects , Male , Female , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/adverse effects , Aged , Thiazoles/therapeutic use , Thiazoles/adverse effects , Thiazoles/administration & dosage , Genomics/methods , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Middle Aged , MutationABSTRACT
BACKGROUND: There is conflicting evidence as to whether intra-arterial thrombolysis (IAT) adds benefit in patients with acute stroke who undergo mechanical thrombectomy (MT). METHODS: We conducted a systematic review to identify studies that evaluate IAT in patients with acute stroke who undergo MT. Data were extracted from relevant studies found through a search of PubMed, Scopus, and Web of Science until February 2023. Statistical pooling with random effects meta-analysis was undertaken to evaluate odds of functional independence, mortality, and near-complete or complete angiographic recanalization with IAT compared to no IAT. RESULTS: A total of 18 studies were included (3 matched, 14 unmatched, and 1 randomized). The odds ratio (OR) for functional independence (modified Rankin Scale: 0-2) at 90 days was 1.14 (95% confidence interval (CI): 0.95-1.37, p = 0.17, 16 studies involving 7572 patients) with IAT with moderate between-study heterogeneity (I2 = 38.1%). The OR for functional independence with IAT was 1.28 (95% CI: 0.92-1.78, p = 0.15) in studies that were either matched or randomized and 1.24 (95% CI: 0.97-1.58, p = 0.08) in studies with the highest quality score. IAT was associated with higher odds of near-complete or complete angiographic recanalization (OR: 1.65, 95% CI: 1.03-2.65, p = 0.04) in studies that were either matched or of randomized comparisons. CONCLUSION: Although the odds of functional independence appeared to be higher with IAT and MT compared with MT alone, none of the results were statistically significant. A prominent effect of the design and quality of the studies was observed on the association between IAT and functional independence at 90 days.