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Nevin Manimala Statistics

Infarct Evolution in Patients with Anterior Circulation Large-Vessel Occlusion Randomized to IV Alteplase and Endovascular Treatment versus Endovascular Treatment Alone

AJNR Am J Neuroradiol. 2023 Mar 23. doi: 10.3174/ajnr.A7826. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Infarct evolution after endovascular treatment varies widely among patients with stroke and may be affected by baseline characteristics and procedural outcomes. Moreover, IV alteplase and endovascular treatment may influence the relationship of these factors to infarct evolution. We aimed to assess whether the infarct evolution between baseline and follow-up imaging was different for patients who received IVT and EVT versus EVT alone.

MATERIALS AND METHODS: We included patients from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN)-NO IV trial with baseline CTP and follow-up imaging. Follow-up infarct volume was segmented on 24-hour or 1-week follow-up DWI or NCCT. Infarct evolution was defined as the follow-up lesion volume: CTP core volume. Substantial infarct growth was defined as an increase in follow-up infarct volume of >10 mL. We assessed whether infarct evolution was different for patients with IV alteplase and endovascular treatment versus endovascular treatment alone and evaluated the association of baseline characteristics and procedural outcomes with infarct evolution using multivariable regression.

RESULTS: From 228 patients with CTP results available, 145 patients had follow-up imaging and were included in our analysis. For patients with IV alteplase and endovascular treatment versus endovascular treatment alone, the baseline median CTP core volume was 17 (interquartile range = 4-35) mL versus 11 (interquartile range = 6-24) mL. The median follow-up infarct volume was 13 (interquartile range, 4-48) mL versus 17 (interquartile range = 4-50) mL. Collateral status and occlusion location were negatively associated with substantial infarct growth in patients with and without IV alteplase before endovascular treatment.

CONCLUSIONS: No statistically significant difference in infarct evolution was found in directly admitted patients who received IV alteplase and endovascular treatment within 4.5 hours of symptom onset versus patients who underwent endovascular treatment alone. Collateral status and occlusion location may be useful predictors of infarct evolution prognosis in patients eligible for IV alteplase who underwent endovascular treatment.

PMID:36958803 | DOI:10.3174/ajnr.A7826

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Direct Aspiration versus Combined Technique for Distal Medium-Vessel Occlusions: Comparison on a Human Placenta Model

AJNR Am J Neuroradiol. 2023 Mar 23. doi: 10.3174/ajnr.A7831. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Mechanical thrombectomy appears to be a promising option for distal medium-vessel occlusions, for which intravenous thrombolysis is effective but may be insufficient when used alone. This study aimed to determine the optimal technique for these distal mechanical thrombectomies using the human placenta model.

MATERIALS AND METHODS: Twenty-four procedures were performed, allowing comparison of direct aspiration (n = 12) versus the combined technique (n = 12). Two positions of the aspiration catheter were tested for each of these techniques: in direct contact with the clot and at a distance from it (5-10 mm). Two types of clots were tested: red blood cell-rich clots and fibrin-rich clots. First-pass recanalization and induced arterial collapse and traction were assessed.

RESULTS: The first-pass recanalization was less frequent for direct aspiration than for the combined technique, without reaching statistical significance (41.7% versus 75.0%, P = .098). Full collapse (P < .001) and extended arterial traction (P = .001) were significantly less frequent for direct aspiration. For direct aspiration with the aspiration catheter not in direct contact with the clot, there was not a single first-pass recanalization and there was systematic arterial collapse, resulting in a no-flow in the aspiration syringe.

CONCLUSIONS: The combined technique appears to be more harmful, and although direct aspiration has a lower rate of first-pass recanalization, it seems appropriate to try direct aspiration as a first-line procedure. However, if the aspiration catheter cannot reach the clot, it is not useful or even risky to try aspiration alone. These results need to be confirmed by clinical studies.

PMID:36958799 | DOI:10.3174/ajnr.A7831

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Clinical Profiles and Patterns of Neurodegeneration in Amyotrophic Lateral Sclerosis: A Cluster-Based Approach Based on MR Imaging Metrics

AJNR Am J Neuroradiol. 2023 Mar 23. doi: 10.3174/ajnr.A7823. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: The previous studies described phenotype-associated imaging findings in amyotrophic lateral sclerosis (ALS) with a prior categorization of patients based on clinical characteristics. We investigated the natural segregation of patients through a radiologic cluster-based approach without a priori patient categorization using 3 well-known prognostic MR imaging biomarkers in ALS, namely bilateral precentral and paracentral gyrus cortical thickness and medulla oblongata volume. We aimed to identify clinical/prognostic features that are cluster-associated.

MATERIALS AND METHODS: Bilateral precentral and paracentral gyri and medulla oblongata volume were calculated using FreeSurfer in 90 patients with amyotrophic lateral sclerosis and 25 healthy controls. A 2-step cluster analysis was performed using precentral and paracentral gyri (averaged pair-wise) and medulla oblongata volume.

RESULTS: We identified 3 radiologic clusters: 28 (31%) patients belonged to “cluster-1”; 51 (57%), to “cluster 2”; and 11 (12%), to “cluster 3.” Patients in cluster 1 showed statistically significant cortical thinning of the analyzed cortical areas and lower medulla oblongata volume compared with subjects in cluster 2 and cluster 3, respectively. Patients in cluster 3 exhibited significant cortical thinning of both paracentral and precentral gyri versus those in cluster 2, and this latter cluster showed lower medulla oblongata volume than cluster 3. Patients in cluster 1 were characterized by older age, higher female prevalence, greater disease severity, higher progression rate, and lower survival compared with patients in clusters 2 and 3.

CONCLUSIONS: Patients with amyotrophic lateral sclerosis spontaneously segregate according to age and sex-specific patterns of neurodegeneration. Some patients with amyotrophic lateral sclerosis showed an early higher impairment of cortical motor neurons with relative sparing of bulbar motor neurons (cluster 3), while others expressed an opposite pattern (cluster 2). Moreover, 31% of patients showed an early simultaneous impairment of cortical and bulbar motor neurons (cluster 1), and they were characterized by higher disease severity and lower survival.

PMID:36958798 | DOI:10.3174/ajnr.A7823

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Interventions to reduce repetitive ordering of low-value inpatient laboratory tests: a systematic review

BMJ Open Qual. 2023 Mar;12(1):e002128. doi: 10.1136/bmjoq-2022-002128.

ABSTRACT

BACKGROUND: Over-ordering of daily laboratory tests adversely affects patient care through hospital-acquired anaemia, patient discomfort, burden on front-line staff and unnecessary downstream testing. This remains a prevalent issue despite the 2013 Choosing Wisely recommendation to minimise unnecessary daily labs. We conducted a systematic review of the literature to identify interventions targeting unnecessary laboratory testing.

METHODS: We systematically searched MEDLINE, EMBASE, Cochrane Central and SCOPUS databases to identify interventions focused on reducing daily complete blood count, complete metabolic panel and basic metabolic panel labs. We defined interventions as ‘effective’ if a statistically significant reduction was attained and ‘highly effective’ if a reduction of ≥25% was attained.

RESULTS: The search yielded 5646 studies with 41 articles that met inclusion criteria. We grouped interventions into one or more categories: audit and feedback, cost display, education, electronic medical record (EMR) change, and policy change. Most interventions lasted less than a year and used a multipronged approach. All five strategies were effective in most studies with EMR change being the most commonly used independent strategy. EMR change and policy change were the strategies most frequently reported as effective. EMR change was the strategy most frequently reported as highly effective.

CONCLUSION: Our analysis identified five categories of interventions targeting daily laboratory testing. All categories were effective in most studies, with EMR change being most frequently highly effective.

PROSPERO REGISTRATION NUMBER: CRD42021254076.

PMID:36958791 | DOI:10.1136/bmjoq-2022-002128

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Mapping Global Bushmeat Activities to Improve Zoonotic Spillover Surveillance by Using Geospatial Modeling

Emerg Infect Dis. 2023 Apr;29(4):742-750. doi: 10.3201/eid2904.221022.

ABSTRACT

Human populations that hunt, butcher, and sell bushmeat (bushmeat activities) are at increased risk for zoonotic pathogen spillover. Despite associations with global epidemics of severe illnesses, such as Ebola and mpox, quantitative assessments of bushmeat activities are lacking. However, such assessments could help prioritize pandemic prevention and preparedness efforts. We used geospatial models that combined published data on bushmeat activities and ecologic and demographic drivers to map the distribution of bushmeat activities in rural regions globally. The resulting map had high predictive capacity for bushmeat activities (true skill statistic = 0.94). The model showed that mammal species richness and deforestation were principal drivers of the geographic distribution of bushmeat activities and that countries in West and Central Africa had the highest proportion of land area associated with bushmeat activities. These findings could help prioritize future surveillance of bushmeat activities and forecast emerging zoonoses at a global scale.

PMID:36957996 | DOI:10.3201/eid2904.221022

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Importance of moderate-to-vigorous physical activity during the COVID-19 pandemic: a systematic review and meta-analysis

J Basic Clin Physiol Pharmacol. 2023 Mar 24. doi: 10.1515/jbcpp-2023-0040. Online ahead of print.

ABSTRACT

Moderate-to-vigorous physical activity (MVPA) has been shown to have a favorable effect on many diseases as a complementary therapy and is a critical component of healthy living. During the pandemic era, physical activity has been promoted for resistance against coronavirus disease 2019 (COVID-19). However, there is scarce evidence on whether MVPA could reduce the infectivity and susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The objective of this meta-analysis was to determine the effect of MVPA on morbidity, mortality, and duration of hospitalization in COVID-19 patients. We performed a comprehensive search of five online databases for eligible studies up to September 9, 2021. Meta-analyses were conducted to determine the association between MVPA and COVID-19-related morbidity, hospitalization, and mortality. The odds ratio (OR) was applied as the summary statistic for the primary outcomes. Secondary analyses were conducted to evaluate the difference in the metabolic equivalent of tasks (METs) between the outcome and non-outcome groups with the mean difference as the pooled effect. This meta-analysis included eight observational studies. We found that MVPA significantly reduced the odds of contracting SARS-CoV-2 infection (OR=0.88; 95% confidence interval [CI] = 0.85-0.92), hospitalization (OR=0.56; 95% CI=0.35-0.92), and mortality (OR=0.42; 95% CI=0.21-0.81) due to COVID-19 compared to no physical activity. METs≥500 min/week were linked to decreased morbidity and mortality of COVID-19 (OR=0.94 [95% CI=0.90-0.98]; OR=0.56 [95% CI=0.38-0.83]). COVID-19 patients with MVPA demonstrated a lower risk of COVID-19-related morbidity, hospitalization, and mortality compared to those who were less active, highlighting the importance of an active lifestyle despite the pandemic situation where such activities are limited.

PMID:36957989 | DOI:10.1515/jbcpp-2023-0040

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Nevin Manimala Statistics

Immediate Fixation of Acetabular Fractures Through an Anterior Approach Does Not Increase Morbidity or Mortality

J Am Acad Orthop Surg. 2023 Mar 23. doi: 10.5435/JAAOS-D-22-00764. Online ahead of print.

ABSTRACT

INTRODUCTION: Acetabular fractures requiring an anterior approach have historically been delayed, allowing a stable clot to form before creating large surgical exposures. The purpose of this study was to determine whether immediate fixation of acetabular fractures within 24 hours using an anterior approach demonstrates notable difference in blood loss, length of stay (LOS), complications, or mortality compared with acetabular fractures treated after 24 hours.

METHODS: Ninety-three patients were optimized for surgery within 24 hours of injury. Thirty-two patients underwent fixation within 24 hours using an anterior approach to the acetabulum. Demographics, hours from injury to operating room, fracture classification, embolization, surgical approach, intraoperative cell salvage use, Charlson Comorbidity Index, American Society of Anesthesiologists class, Injury Severity Score, and Abbreviated Chest Injury Score were recorded. Estimated blood loss, transfusions, intensive care unit stay, total hospital LOS, complications, and mortality rates were compared.

RESULTS: No statistically significant differences were observed in fracture classification, blood loss, or intraoperative transfusions between the immediate and delayed fixation groups. Six patients in the delayed group (9.8%) returned to the operating room for a complication compared with one patient (3.1%) in the immediate group (P = 0.42). Three patients in the delayed group (4.9%) developed a surgical site infection compared with none (0%) in the immediate group (P = 0.55). The immediate group had an average LOS of 7 days compared with 11 days in the delayed fixation group (P = 0.01). No notable differences were observed in 30- or 90-day mortality rates.

DISCUSSION: Medically optimized patients with acetabular fractures who undergo immediate fixation through an anterior approach do not seem to have an associated increase in blood loss, transfusions, or mortality. Prompt surgical management may also be associated with a shorter preoperative and postoperative LOS.

LEVEL OF EVIDENCE: Therapeutic level III.

PMID:36952666 | DOI:10.5435/JAAOS-D-22-00764

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Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer

J Clin Oncol. 2023 Mar 23:JCO2201649. doi: 10.1200/JCO.22.01649. Online ahead of print.

ABSTRACT

PURPOSE: Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with current standard-of-care therapies. Homologous recombination repair (HRR) gene alterations, including BRCA1/2 alterations, can sensitize cancer cells to poly (ADP-ribose) polymerase inhibition, which may improve outcomes in treatment-naïve mCRPC when combined with androgen receptor signaling inhibition.

METHODS: MAGNITUDE (ClinicalTrials.gov identifier: NCT03748641) is a phase III, randomized, double-blinded study that evaluates niraparib and abiraterone acetate plus prednisone (niraparib + AAP) in patients with (HRR+, n = 423) or without (HRR-, n = 247) HRR-associated gene alterations, as prospectively determined by tissue/plasma-based assays. Patients were assigned 1:1 to receive niraparib + AAP or placebo + AAP. The primary end point, radiographic progression-free survival (rPFS) assessed by central review, was evaluated first in the BRCA1/2 subgroup and then in the full HRR+ cohort, with secondary end points analyzed for the full HRR+ cohort if rPFS was statistically significant. A futility analysis was preplanned in the HRR- cohort.

RESULTS: Median rPFS in the BRCA1/2 subgroup was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.6 v 10.9 months; hazard ratio [HR], 0.53; 95% CI, 0.36 to 0.79; P = .001). In the overall HRR+ cohort, rPFS was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.5 v 13.7 months; HR, 0.73; 95% CI, 0.56 to 0.96; P = .022). These findings were supported by improvement in the secondary end points of time to symptomatic progression and time to initiation of cytotoxic chemotherapy. In the HRR- cohort, futility was declared per the prespecified criteria. Treatment with niraparib + AAP was tolerable, with anemia and hypertension as the most reported grade ≥ 3 adverse events.

CONCLUSION: Combination treatment with niraparib + AAP significantly lengthened rPFS in patients with HRR+ mCRPC compared with standard-of-care AAP.

PMID:36952634 | DOI:10.1200/JCO.22.01649

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Software Application Profile: The daggle app-a tool to support learning and teaching the graphical rules of selecting adjustment variables using directed acyclic graphs

Int J Epidemiol. 2023 Mar 23:dyad038. doi: 10.1093/ije/dyad038. Online ahead of print.

ABSTRACT

MOTIVATION: Directed acyclic graphs (DAGs) are used in epidemiological research to communicate causal assumptions and guide the selection of covariate adjustment sets when estimating causal effects. For any given DAG, a set of graphical rules can be applied to identify minimally sufficient adjustment sets that can be used to adjust for bias due to confounding when estimating the causal effect of an exposure on an outcome. The daggle app is a web-based application that aims to assist in the learning and teaching of adjustment set identification using DAGs.

GENERAL FEATURES: The application offers two modes: tutorial and random. The tutorial mode presents a guided introduction to how common causal structures can be presented using DAGs and how graphical rules can be used to identify minimally sufficient adjustment sets for causal estimation. The random mode tests this understanding by presenting the user with a randomly generated DAG-a daggle. To solve the daggle, users must correctly identify a valid minimally sufficient adjustment set.

IMPLEMENTATION: The daggle app is implemented as an R shiny application using the golem framework. The application builds upon existing R libraries including pcalg to generate reproducible random DAGs, dagitty to identify all valid minimal adjustment sets and ggdag to visualize DAGs.

AVAILABILITY: The daggle app can be accessed online at [http://cbdrh.shinyapps.io/daggle]. The source code is available on GitHub [https://github.com/CBDRH/daggle] and is released under a Creative Commons CC BY-NC-SA 4.0 licence.

PMID:36952629 | DOI:10.1093/ije/dyad038

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Is micronucleus assay a suitable method for biomonitoring children exposed to X-ray? A systematic review with meta-analysis

Int J Radiat Biol. 2023 Mar 23:1-16. doi: 10.1080/09553002.2023.2194405. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study was to evaluate if the micronucleus test using oral epithelial cells is a suitable biomarker for biomonitoring children exposed to X-ray.

MATERIAL AND METHODS: A search was performed through the electronic databases PubMed/Medline, Scopus and Web of Science, all studies published up to February 2022 that examined the relationship between exposure of children to radiographic examinations and micronucleus.

RESULTS: The initial search in the electronic databases identified 108 records. 91 records were excluded because they were repeated or not related to the study. A total of 17 full-text manuscripts were screened for eligibility. Finally, a total of nine manuscripts met the inclusion criteria in the SR and six were included in the meta-analysis. Only two studies found a difference in micronucleus labeling. On the other hand, all studies showed that X-ray was able to induce cellular death in oral mucosa cells. Following the parameters of the Effective Practices in Public Health Project (EPHPP), five manuscripts reached moderate and strong scores, and four studies were categorized as weak at final rating. In the meta-analysis, the diamond advanced more towards the increase of micronuclei after the radiographic examination. With a statistically significant difference in micronucleated cells in children before and after radiographic examinations (SMD = 0.96, 95% CI, 0.07 to 1.84, p = 0.04), with Tau2=1.09; Chi2=53.37, and p < 0.001.

CONCLUSION: Radiographic examinations in children can cause genotoxic and cytotoxic damage in the oral epithelium with a large effect size.

PMID:36952616 | DOI:10.1080/09553002.2023.2194405