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NRG Oncology/RTOG1205: A Randomized Phase II Trial of Concurrent Bevacizumab and Reirradiation Versus Bevacizumab Alone as Treatment for Recurrent Glioblastoma

J Clin Oncol. 2022 Oct 19:JCO2200164. doi: 10.1200/JCO.22.00164. Online ahead of print.

ABSTRACT

PURPOSE: To assess whether reirradiation (re-RT) and concurrent bevacizumab (BEV) improve overall survival (OS) and/or progression-free survival (PFS), compared with BEV alone in recurrent glioblastoma (GBM). The primary objective was OS, and secondary objectives included PFS, response rate, and treatment adverse events (AEs) including delayed CNS toxicities.

METHODS: NRG Oncology/RTOG1205 is a prospective, phase II, randomized trial of re-RT and BEV versus BEV alone. Stratification factors included age, resection, and Karnofsky performance status (KPS). Patients with recurrent GBM with imaging evidence of tumor progression ≥ 6 months from completion of prior chemo-RT were eligible. Patients were randomly assigned 1:1 to re-RT, 35 Gy in 10 fractions, with concurrent BEV IV 10 mg/kg once in every 2 weeks or BEV alone until progression.

RESULTS: From December 2012 to April 2016, 182 patients were randomly assigned, of whom 170 were eligible. Patient characteristics were well balanced between arms. The median follow-up for censored patients was 12.8 months. There was no improvement in OS for BEV + RT, hazard ratio, 0.98; 80% CI, 0.79 to 1.23; P = .46; the median survival time was 10.1 versus 9.7 months for BEV + RT versus BEV alone. The median PFS for BEV + RT was 7.1 versus 3.8 months for BEV, hazard ratio, 0.73; 95% CI, 0.53 to 1.0; P = .05. The 6-month PFS rate improved from 29.1% (95% CI, 19.1 to 39.1) for BEV to 54.3% (95% CI, 43.5 to 65.1) for BEV + RT, P = .001. Treatment was well tolerated. There were a 5% rate of acute grade 3+ treatment-related AEs and no delayed high-grade AEs. Most patients died of recurrent GBM.

CONCLUSION: To our knowledge, NRG Oncology/RTOG1205 is the first prospective, randomized multi-institutional study to evaluate the safety and efficacy of re-RT in recurrent GBM using modern RT techniques. Overall, re-RT was shown to be safe and well tolerated. BEV + RT demonstrated a clinically meaningful improvement in PFS, specifically the 6-month PFS rate but no difference in OS.

PMID:36260832 | DOI:10.1200/JCO.22.00164

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The National Response to Patients with Acute Coronary Syndrome during the First Wave of the COVID-19 Pandemic in Portugal

Acta Med Port. 2022 Oct 19. doi: 10.20344/amp.18610. Online ahead of print.

ABSTRACT

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to changes in healthcare institutions and medical assistance. Non-SARS-CoV-2 related diseases were indirectly affected by the pandemic. Nonetheless, their treatment remains crucial. Cardiovascular conditions such as acute coronary syndrome (ACS) are common, and it was necessary to adjust medical assistance to these diseases during the pandemic. This study aimed to assess the national impact and healthcare system response during the first wave of the pandemic in patients admitted for ACS.

MATERIAL AND METHODS: Multicenter retrospective study based on the Acute Coronary Syndrome Portuguese National Registry between the 1st January 2016 and the 28th February 2021. Two groups were defined: the previous year to the SARS-CoV-2 pandemic (March, April, May and June 2019) (952 patients) and the first wave of the pandemic (March, April, May and June 2020) (642 patients). Clinical course, time until reperfusion, in-hospital outcomes and follow-up at one year were compared between both periods.

RESULTS: There was a lower incidence of ACS between March and June 2020 compared with the same period in 2019, with a reduction of 32.6%. There were no statistically significant differences between the two periods regarding patient demographic characteristics (except for a higher prevalence of familiar cardi vascular history and chronic obstructive pulmonary disease in 2020 and higher prevalence of diabetes in 2019), clinical features, clinical management, in-hospital major adverse cardiac events, mortality and readmission at one-year follow-up. There was a trend towards longer delays until reperfusion, yet without statistical significance. The patients that developed ACS during the first wave of the SARS-CoV-2 pandemic were less often referred to percutaneous coronary intervention centers (p = 0.034) and were more frequently transferred to another hospital (p < 0.001).

CONCLUSION: During the first wave of the SARS-CoV-2 pandemic there was a nationwide reduction in demand of healthcare services due to ACS events. Even though the Portuguese healthcare system was under strain and forced to divert resources and medical assistance towards the pandemic management, it was capable of responding adequately to ACS.

PMID:36260808 | DOI:10.20344/amp.18610

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Prehospital Pediatric Asthma Care during COVID-19: Changes to EMS Treatment Protocols and Downstream Clinical Effects

Prehosp Emerg Care. 2022 Oct 19:1-13. doi: 10.1080/10903127.2022.2137864. Online ahead of print.

ABSTRACT

INTRODUCTION: During the COVID-19 pandemic, many emergency medical services (EMS) agencies modified treatment guidelines for clinical care and standard operating procedures. For the prehospital care of pediatric asthma exacerbations, modifications included changes to bronchodilator administration, systemic corticosteroid administration, and introduction of alternative medications. Since timely administration of bronchodilators and systemic corticosteroids has been shown to improve pediatric asthma clinical outcomes, we investigated the association of COVID-19 protocol modifications in the prehospital management of pediatric asthma on hospital admission rates and emergency department (ED) length-of-stay.

METHODS: This is a multicenter, retrospective, observational cohort study comparing prehospital pediatric asthma patients treated by EMS clinicians from four EMS systems before and after implementation of COVID-19 interim EMS protocol modifications. We included children ages 2 – 18 years who were treated and transported by ground EMS for respiratory-related prehospital primary complaints, and who also had asthma-related ED discharge diagnoses. Patient data and outcomes were compared from 12 months prior to and 12 months after the implementation of interim COVID-19 prehospital protocol modifications using univariate and multivariable statistics.

RESULTS: A total of 430 patients met inclusion criteria with a median age of 8 years. There was a slight male predominance (57.9%) and the majority of patients were African American (78.4%). There were twice as many patients treated prior to the COVID-19 protocol modifications (N = 287) compared to after (N = 143). There was a significant decrease in EMS bronchodilator administration from 76% to 59.4% of patients after COVID-19 protocol guidelines were implemented (p < 0.0001). Mixed effects models for hospital admission (to both pediatric inpatient units and pediatric intensive care units) as well as ED length-of-stay did not show any significant effect after the COVID-19 protocol change period (p = 0.18 and p = 0.55, respectively).

CONCLUSIONS: Despite a decrease in prehospital bronchodilator administration after COVID-19 changes to prehospital pediatric asthma management protocols, hospital admission rates and ED length-of-stay did not significantly increase. However, this finding is tempered by the marked decrease in study patients treated after COVID-19 prehospital protocol modifications. Given the potential for future waves of COVID-19 variants, further studies with larger patient populations are warranted.

PMID:36260781 | DOI:10.1080/10903127.2022.2137864

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Emergency Medical Services Clinicians Have a High Prevalence of Metabolic Syndrome

Prehosp Emerg Care. 2022 Oct 19:1-12. doi: 10.1080/10903127.2022.2138655. Online ahead of print.

ABSTRACT

Background: Metabolic syndrome is a constellation of risk factors associated with the development of cardiovascular disease and increased all-cause mortality. Data examining the prevalence of metabolic syndrome among emergency medical services (EMS) clinicians are limited.Methods: We conducted a cross-sectional study of EMS clinicians and firefighters from three fire departments with transport-capable EMS divisions. Data were collected from compulsory annual physical exams for 2021 that included age, sex, race, body mass index (BMI), waist circumference, blood pressure, cholesterol levels, and hemoglobin A1c level. These data were used to determine the prevalence of meeting metabolic syndrome criteria. We calculated descriptive statistics of demographics, anthropometrics, and metabolic syndrome criteria for EMS clinicians and firefighters. We used chi-square tests to compare the proportion of EMS clinicians and firefighters meeting criteria for the whole group and among age groups of <40 years old, 40 to 59 years old, and ≥60 years old. We used logistic regression to estimate the odds of meeting criteria in EMS clinicians compared to firefighters, adjusted for age, sex, race, and BMI.Results: We reviewed data for 65 EMS clinicians and 239 firefighters. For the combined cohort, 13.2% (40/304) were female and 95.1% (289/304) were White. The median age for EMS clinicians was 34 years versus 45 years in firefighters (p < 0.0001). Metabolic syndrome criteria were met in 27.3% (83/304) of the entire group. The prevalence of meeting criteria among EMS clinicians and firefighters was 33.9% (22/65) and 25.5% (61/239), respectively (p = 0.18). Of the participants who were younger than age 40, 36.6% (15/41) of EMS clinicians versus 9.1% (7/74) of firefighters met criteria for metabolic syndrome (p < 0.001). EMS clinicians had significantly higher odds of meeting criteria [OR 4.62 (p = 0.001)] compared to firefighters when adjusted for age, sex, race, and BMI.Conclusion: EMS clinicians had a high prevalence of metabolic syndrome at an early age, and had a higher adjusted odds of having metabolic syndrome compared to firefighters.

PMID:36260778 | DOI:10.1080/10903127.2022.2138655

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Are Video Recordings Reliable for Assessing Surgical Performance? A Prospective Reliability Study Using Generalizability Theory

Simul Healthc. 2022 Oct 18. doi: 10.1097/SIH.0000000000000672. Online ahead of print.

ABSTRACT

INTRODUCTION: Reliability is pivotal in surgical skills assessment. Video-based assessment can be used for objective assessment without physical presence of assessors. However, its reliability for surgical assessments remains largely unexplored. In this study, we evaluated the reliability of video-based versus physical assessments of novices’ surgical performances on human cadavers and 3D-printed models-an emerging simulation modality.

METHODS: Eighteen otorhinolaryngology residents performed 2 to 3 mastoidectomies on a 3D-printed model and 1 procedure on a human cadaver. Performances were rated by 3 experts evaluating the final surgical result using a well-known assessment tool. Performances were rated both hands-on/physically and by video recordings. Interrater reliability and intrarater reliability were explored using κ statistics and the optimal number of raters and performances required in either assessment modality was determined using generalizability theory.

RESULTS: Interrater reliability was moderate with a mean κ score of 0.58 (range 0.53-0.62) for video-based assessment and 0.60 (range, 0.55-0.69) for physical assessment. Video-based and physical assessments were equally reliable (G coefficient 0.85 vs. 0.80 for 3D-printed models and 0.86 vs 0.87 for cadaver dissections). The interaction between rater and assessment modality contributed to 8.1% to 9.1% of the estimated variance. For the 3D-printed models, 2 raters evaluating 2 video-recorded performances or 3 raters physically assessing 2 performances yielded sufficient reliability for high-stakes assessment (G coefficient >0.8).

CONCLUSIONS: Video-based and physical assessments were equally reliable. Some raters were affected by changing from physical to video-based assessment; consequently, assessment should be either physical or video based, not a combination.

PMID:36260767 | DOI:10.1097/SIH.0000000000000672

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Is conservative management of partial zone II flexor tendon laceration possible? A systematic literature review and meta-analysis

J Plast Surg Hand Surg. 2022 Oct 19:1-8. doi: 10.1080/2000656X.2022.2117704. Online ahead of print.

ABSTRACT

Background: There is still no consensus on managing zone II level partial flexor tendon lacerations, and the management of zone II partial flexor tendon injuries is controversial. No reliable large cohort studies or metaanalysis papers on partial flexor tendon laceration management are available in PubMed or Embase.Methods: We searched PubMed, Embase, Cochrane Library, Insight, Scopus, and Web of Science databases for primary research articles investigating outcomes of patients with partial flexor tendon injuries. The initial search was limited to human studies that were published from 1970-2021 and indexed as randomized controlled or clinical trials or observational, cross-sectional, or cohort studies. We used statistical package R version 4.1.2 for this meta-analysis.Results: The Standardised mean difference (SMD) of the common effects model was 2.020 (95% CI; 1.583-2.457; P < 0.0001), indicating that the results of conservative treatment without surgical intervention are similar to surgical intervention or better in some articles. The SMD of the random effect model was 7.093 (95% CI; 1.090-13.096; P < 0.0206), indicating the same result. Higgins’ I2 value was 97.6%, indicating serious heterogeneity.Conclusions: In this first meta-analysis on flexor zone II conservative treatment, five papers with publication bias were analyzed. It is meaningful to verify the result of conservative treatment statistically. Even though this is a heterogeneous paper, conservative treatment seems to have a lot of benefits for the patient, including offering a fairly solid longterm prognosis with very few complications.

PMID:36260732 | DOI:10.1080/2000656X.2022.2117704

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Models with higher effective dimensions tend to produce more uncertain estimates

Sci Adv. 2022 Oct 21;8(42):eabn9450. doi: 10.1126/sciadv.abn9450. Epub 2022 Oct 19.

ABSTRACT

Mathematical models are getting increasingly detailed to better predict phenomena or gain more accurate insights into the dynamics of a system of interest, even when there are no validation or training data available. Here, we show through ANOVA and statistical theory that this practice promotes fuzzier estimates because it generally increases the model’s effective dimensions, i.e., the number of influential parameters and the weight of high-order interactions. By tracking the evolution of the effective dimensions and the output uncertainty at each model upgrade stage, modelers can better ponder whether the addition of detail truly matches the model’s purpose and the quality of the data fed into it.

PMID:36260678 | DOI:10.1126/sciadv.abn9450

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Mapping of machine learning approaches for description, prediction, and causal inference in the social and health sciences

Sci Adv. 2022 Oct 21;8(42):eabk1942. doi: 10.1126/sciadv.abk1942. Epub 2022 Oct 19.

ABSTRACT

Machine learning (ML) methodology used in the social and health sciences needs to fit the intended research purposes of description, prediction, or causal inference. This paper provides a comprehensive, systematic meta-mapping of research questions in the social and health sciences to appropriate ML approaches by incorporating the necessary requirements to statistical analysis in these disciplines. We map the established classification into description, prediction, counterfactual prediction, and causal structural learning to common research goals, such as estimating prevalence of adverse social or health outcomes, predicting the risk of an event, and identifying risk factors or causes of adverse outcomes, and explain common ML performance metrics. Such mapping may help to fully exploit the benefits of ML while considering domain-specific aspects relevant to the social and health sciences and hopefully contribute to the acceleration of the uptake of ML applications to advance both basic and applied social and health sciences research.

PMID:36260666 | DOI:10.1126/sciadv.abk1942

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Causal inference from text: A commentary

Sci Adv. 2022 Oct 21;8(42):eade6585. doi: 10.1126/sciadv.ade6585. Epub 2022 Oct 19.

ABSTRACT

Statistical and machine learning methods help social scientists and other researchers make causal inferences from texts.

PMID:36260667 | DOI:10.1126/sciadv.ade6585

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Differences in the management of patients requiring an emergency resection for colonic cancer in two European populations

BJS Open. 2022 Sep 2;6(5):zrac126. doi: 10.1093/bjsopen/zrac126.

ABSTRACT

BACKGROUND: Patients with colonic cancer who require emergency colonic cancer surgery often experience poorer outcomes compared with their elective counterparts. In this setting, several treatments approaches are available. In 2009, Danish guidelines recommended treatment with stent for obstruction in left-sided tumours as a bridge to surgery, if expertise is accessible. The aim of this study was to compare the use of elective and emergency resections for colonic cancer and postoperative mortality in two similar demographic populations.

METHODS: All patients who underwent a major resection for colonic cancer, between 2005 and 2016 in Denmark and Yorkshire (UK) were identified. The proportion undergoing emergency surgery, the proportion receiving a stent procedure before their resection, and 30-day postoperative mortality were compared between the populations. Logistic regression was used to determine changes in the proportion of those undergoing emergency surgery and 30-day postoperative mortality.

RESULTS: Out of 45 397 patients treated during the study interval, 41 880 were selected. Emergency surgery decreased in Denmark from 16.6 per cent in 2005-07 to 12.9 per cent in 2014-16, but increased in Yorkshire (13.5 per cent to 16.8 per cent). Danish patients with left-sided tumours were less likely to undergo emergency surgery (risk ratio 0.90, 95 per cent c.i. 0.82 to 0.99) and an increase in stent use coincided with a statistically significant decrease in emergency surgery in these patients. Thirty-day postoperative mortality in all resections (elective and emergency) decreased in both populations, but a larger decrease was observed in Denmark (7.7 per cent to 3.0 per cent in Denmark and 7.1 per cent to 3.3 per cent in Yorkshire).

CONCLUSION: Patients in Denmark experienced a reduction in the use of emergency resection and increase in stenting procedures, following the policy implemented in some departments of converting potential emergency resections into elective resections.

PMID:36260651 | DOI:10.1093/bjsopen/zrac126