tbuckley/cabot-search huggingface dataset:
Abstract 10611: Variation in Out-of-Hospital Cardiac Arrest Survival Across EMS Agencies
Authors: R Garcia, Bryan McNally, Saket Girotra, Paul S Chan
Journal: Circulation (2021)

Background: Although some studies have reported variation in out-of-hospital cardiac arrest (OHCA) survival by neighborhood and geographic region, little is known about variation in OHCA survival at the level of EMS agencies—which, unlike neighborhoods and regions, may have modifiable resuscitation practices. Methods: Within the national Cardiac Arrest Registry to Enhance Survival, we identified 258,320 non-traumatic OHCAs from 764 EMS agencies with ≥10 OHCAs annually between 2015-2019. Using multivariable hierarchical logistic regression, we computed risk-adjusted rates of survival to hospital admission for each EMS agency. We quantified the extent of variation in survival with the median odds ratios (MOR) and assessed the extent to which variation in survival was explained by two EMS agency resuscitation practices: time from 911 call to EMS arrival and the proportion of OHCAs at each EMS agency with termination of resuscitation (TOR) without meeting TOR futility criteria. Results: Of 258,320 persons with OHCA, mean age was 62.2 ± 17.0 years and 36.1% were female. Overall, 85.0% were of presumed cardiac etiology, 82.3% occurred at home, 44.0% were witnessed by a bystander, and ~75% were due to a non-shockable initial rhythm. Across the 764 EMS agencies, the median risk-adjusted rate of survival to hospital admission was 27.4% (IQR, 24.5% - 30.2%). The adjusted MOR was 1.35 (95% CI: 1.32, 1.39), suggesting that the odds of survival to hospital admission after an OHCA varied by 35% in two identical patients in one randomly selected EMS agency vs. another. EMS agencies in the lowest quartile of risk-adjusted survival had a mean EMS response time of 12.0 ± 3.4 minutes, whereas those in the highest quartile had a mean EMS response time of 9.0 ± 2.6 minutes ( P &lt;0.001). The mean proportion of OHCA cases where CPR was terminated in the field without meeting TOR futility criteria was 27.9% ±16.1% in quartile 1 and 18.9% ±11.4% in quartile 4 ( P &lt;0.001). Adjustment for the EMS-level variation in both resuscitation practices attenuated the MOR to 1.30 (95% CI: 1.27, 1.33). Conclusions: Rates of survival to hospital admission for OHCA vary significantly by EMS agency, and some of this variation in survival is explained by differences in EMS arrival time and TOR practice patterns.
Grit and Burnout in the Physician Workforce
Authors: Erene Stergiopoulos, Juveria Zaheer, Lisa M. Meeks
Journal: JAMA Surgery (2021)

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Implementation of State Vaccine Incentive Lottery Programs and Uptake of COVID-19 Vaccinations in the United States
Authors: Binod Acharya, Chandra Dhakal
Journal: JAMA Network Open (2021)

<h3>Importance</h3> There is limited evidence on whether COVID-19 vaccine incentive lotteries help to increase vaccine uptake. <h3>Objective</h3> To estimate whether and to what extent statewide implementation of lottery programs is associated with COVID-19 vaccine uptake. <h3>Design, Setting, and Participants</h3> This cross-sectional study used data from 403 714 adults who answered the question, "have you received a COVID-19 vaccine?" on the Household Pulse Survey (HPS) and state-level daily vaccination rates for 11 states implementing a vaccine lottery program (ie, treated states) and 28 states with no such program (ie, control states). A difference-in-difference (DiD) analysis used responses to the HPS question and compared changes in vaccine uptake between treated and control states. The augmented synthetic control (ASC) analysis compared state-level daily new vaccination rates in treated states with their synthetic versions constructed from a donor pool of control states. Data were analyzed from March 17 to July 5, 2021. <h3>Exposures</h3> Announcement of the vaccine lottery programs and states implementing such programs. <h3>Main Outcomes and Measures</h3> The outcome variable in the DiD analysis was the binary indicator of self-reported vaccination status. In the ASC analysis, it was the state-level daily new first vaccine dose administered per 100 000 people (logarithm scale). <h3>Results</h3> A total of 403 714 individuals (mean [SD] age, 52.7 [15.7] years; 239 563 [weighted percentage, 51.6%] women; 31 746 [weighted percentage, 11.9%] Black; 39 709 [weighted percentage, 18.2%] Hispanic; 334 034 [weighted percentage, 76.4%] White) responded to the question in HPS regarding vaccination status. Overall, 80 949 respondents (weighted percentage, 28.1%) in the HPS were unvaccinated. A pooled analysis from both methods indicated that the lottery programs were associated with increased vaccinations. The ASC analysis revealed that lottery programs were associated with an increase of 0.208 log points (95% CI, 0.004-0.412 log points), implying an average 23.12% increment in the new daily vaccination rate. In state-specific analyses, both methods suggested that the vaccine lottery programs were helpful in Ohio (0.09 log points;<i>P</i> &lt; .001), Maryland (0.26 log points;<i>P</i> &lt; .001), Oregon (0.15 log points;<i>P</i> = .002), and Washington (0.37 log points;<i>P</i> &lt; .001) but not in Arkansas, Kentucky, and West Virginia. The ASC analysis found that lottery programs were positively associated with vaccinations in New Mexico (0.32 log points;<i>P</i> &lt; .001) and New York (0.33 log points;<i>P</i> = .001). <h3>Conclusions and Relevance</h3> The findings of this study suggest that lottery programs may be associated with decreased COVID-19 vaccine hesitancy, but that success might differ across states. The findings could also be useful in the ongoing debate on persuading US residents who are not yet vaccinated.
EPCO-17. METHYLATION ANALYSIS OF MATCHED PRIMARY AND RECURRENT IDHmt ASTROCYTOMA; AN UPDATE FROM THE GLIOMA LONGITUDINAL ANALYSIS NL (GLASS-NL) CONSORTIUM
Authors: Wies Vallentgoed, Anneke Niers, Karin van  Garderen, Martin van den Bent, Kaspar Draaisma, Iris de Heer, Mathilde Kouwenhoven, Johan Kros, Ivonne Martin, Pierre Robe, Marion Smits, Mircea Tesileanu, Hinke van Thuijl, Roel Verhaak, Bart Westerman, Mark van de Wiel, Bauke Ylstra, Wendy de Leng, Pieter Wesseling, Pim French
Journal: Neuro-Oncology (2021)

Abstract The GLASS-NL consortium, was initiated to gain insight into the molecular mechanisms underlying glioma evolution and to identify markers of progression in IDH-mutant astrocytomas. Here, we present the first results of genome-wide DNA-methylation profiling of GLASS-NL samples. 110 adult patients were identified with an IDH-mutant astrocytoma at first diagnosis. All patients underwent a surgical resection of the tumor at least twice, separated by at least 6 months (median 40.9 months (IQR: 24.0, 64.7). In 37% and 18% of the cases, patients were treated with radiotherapy or chemotherapy respectively, before surgical resection of the recurrent tumor. DNA-methylation profiling was done on 235 samples from 103 patients (102 1st, 101 2nd, 29 3rd, and 3 4th resection). Copy number variations were also extracted from these data. Methylation classes were determined according to Capper et al. Overall survival (OS) was measured from date of first surgery. Of all primary tumors, the methylation-classifier assigned 85 (87%) to the low grade subclass and 10 (10%) to the high grade subclass. The relative proportion of high grade tumors increased ~three-fold at tumor recurrence (32/101, 32%) and even further in the second recurrence (15/29, 52%). Methylation classes were prognostic, both in primary and recurrent tumors. The overall DNA-methylation levels of recurrent samples was lower than that of primary samples. This difference is explained by the increased number of high grade samples at recurrence, since near identical DNA-methylation levels were observed in samples that remained low grade. In an unsupervised analysis, DNA-methylation data derived from primary and first recurrence samples of individual patients mostly (79%) cluster together. Recurrent samples that do not cluster with their primary tumor, form a separate group with relatively low genome-wide DNA-methylation. Our data demonstrate that methylation profiling identifies a shift towards a higher grade at tumor progression coinciding with reduced genome-wide DNA-methylation levels.
Associations of Serum Testosterone and Sex Hormone–Binding Globulin With Incident Cardiovascular Events in Middle-Aged to Older Men
Authors: Bu B. Yeap, Ross J. Marriott, Leen Antonio, Suchitra Raj, Girish Dwivedi, Christopher M. Reid, Bradley D. Anawalt, Shalender Bhasin, Adrian S. Dobs, David J. Handelsman, Graeme J. Hankey, Robin Haring, Alvin M. Matsumoto, Paul E. Norman, Terence W. O’Neill, Claes Ohlsson, Eric S. Orwoll, Dirk Vanderschueren, Gary A. Wittert, Frederick C.W. Wu, Kevin Murray
Journal: Annals of Internal Medicine (2021)

The influence of testosterone on risk for cardiovascular events in men is uncertain. Previous observational studies of sex hormones and incident cardiovascular disease in men have reported inconsistent findings, limited by cohort sizes and different selection criteria.To analyze associations of serum total testosterone and sex hormone-binding globulin (SHBG) with incident cardiovascular events in men.Cohort study.UK Biobank prospective cohort.Community-dwelling men aged 40 to 69 years.Testosterone and SHBG were assayed, and free testosterone was calculated. Cox proportional hazards regression was done, with outcomes of incident myocardial infarction (MI), hemorrhagic stroke (HS), ischemic stroke (IS), heart failure (HF), and major adverse cardiovascular events (MACE), adjusted for sociodemographic, lifestyle, and medical factors.Of 210 700 men followed for 9 years, 8790 (4.2%) had an incident cardiovascular event. After adjustment for key variables, lower total testosterone concentrations (quintile 1 vs. quintile 5) were not associated with incident MI (fully adjusted hazard ratio [HR], 0.89 [95% CI, 0.80 to 1.00]), HS (HR, 0.94 [CI, 0.70 to 1.26]), IS (HR, 0.95 [CI, 0.82 to 1.10]), HF (HR, 1.15 [CI, 0.91 to 1.45]), or MACE (HR, 0.92 [CI, 0.84 to 1.00]). Men with lower calculated free testosterone values had a lower incidence of MACE (HR, 0.90 [CI, 0.84 to 0.97]). Lower SHBG concentrations were associated with higher incidence of MI (HR, 1.23 [CI, 1.09 to 1.38]) and lower incidence of IS (HR, 0.79 [CI, 0.67 to 0.94]) and HF (HR, 0.69 [CI, 0.54 to 0.89]), but not with HS (HR, 0.81 [CI, 0.57 to 1.14]) or MACE (HR, 1.01 [CI, 0.92 to 1.11]).Observational study; single baseline measurement of testosterone and SHBG.Men with lower total testosterone concentrations were not at increased risk for MI, stroke, HF, or MACE. Calculated free testosterone may be associated with risk for MACE. Men with lower SHBG concentrations have higher risk for MI but lower risk for IS and HF, with causality to be determined.Western Australian Health Translation Network, Medical Research Future Fund, and Lawley Pharmaceuticals.
Adherence to a MIND-Like Dietary Pattern, Long-Term Exposure to Fine Particulate Matter Air Pollution, and MRI-Based Measures of Brain Volume: The Women’s Health Initiative Memory Study-MRI
Authors: Cheng Chen, Kathleen M. Hayden, Joel D. Kaufman, Mark A. Espeland, Eric A. Whitsel, Marc L. Serre, William Vizuete, Tonya S. Orchard, Xinhui Wang, Helena C. Chui, Mary E. D’Alton, Jiu-Chiuan Chen, Ka Kahe
Journal: Environmental Health Perspectives (2021)

Background: Previous studies suggest that certain dietary patterns and constituents may be beneficial to brain health. Airborne exposures to fine particulate matter [particulate matter with aerodynamic diameter ≤2.5μm (PM2.5)] are neurotoxic, but the combined effects of dietary patterns and PM2.5 have not been investigated. Objectives: We examined whether previously reported association between PM2.5 exposure and lower white matter volume (WMV) differed between women whose usual diet during the last 3 months before baseline was more or less consistent with a Mediterranean–DASH Intervention for Neurodegenerative Delay (MIND)-like diet, a dietary pattern that may slow neurodegenerative changes. Methods: This study included 1,302 U.S. women who were 65–79 y old and free of dementia in the period 1996–1998 (baseline). In the period 2005–2006, structural brain magnetic resonance imaging (MRI) scans were performed to estimate normal-appearing brain volumes (excluding areas with evidence of small vessel ischemic disease). Baseline MIND diet scores were derived from a food frequency questionnaire. Three-year average PM2.5 exposure prior to MRI was estimated using geocoded participant addresses and a spatiotemporal model. Results: Average total and temporal lobe WMVs were 0.74 cm3 [95% confidence interval (CI): 0.001, 1.48) and 0.19 cm3 (95% CI: 0.002, 0.37) higher, respectively, with each 0.5-point increase in the MIND score and were 4.16 cm3 (95% CI: –6.99, –1.33) and 1.46 cm3 (95% CI: –2.16, –0.76) lower, respectively, with each interquartile range (IQR) (IQR=3.22 μg/m3) increase in PM2.5. The inverse association between PM2.5 per IQR and WMV was stronger (p-interaction<0.001) among women with MIND scores below the median (for total WMV, –12.47 cm3; 95% CI: −17.17, −7.78), but absent in women with scores above the median (0.16 cm3; 95% CI: −3.41, 3.72), with similar patterns for WMV in the frontal, parietal, and temporal lobes. For total cerebral and hippocampus brain volumes or WMV in the corpus callosum, the associations with PM2.5 were not significantly different for women with high MIND scores and women with low MIND scores. Discussion: In this cohort of U.S. women, PM2.5 exposure was associated with lower MRI-based WMV, an indication of brain aging, only among women whose usual diet was less consistent with the MIND-like dietary pattern at baseline. https://doi.org/10.1289/EHP8036
Clinical utility of targeted next-generation sequencing assay in IDH-wildtype glioblastoma for therapy decision-making
Authors: Mary Jane Lim-Fat, Gilbert C Youssef, Mehdi Touat, J Bryan Iorgulescu, Sydney Whorral, Marie Allen, Rifaquat Rahman, Ugonma Chukwueke, J Ricardo McFaline-Figueroa, Lakshmi Nayak, Eudocia Q Lee, Tracy T Batchelor, Omar Arnaout, Pier Paolo Peruzzi, E Antonio Chiocca, David A Reardon, David Meredith, Sandro Santagata, Rameen Beroukhim, Wenya Linda Bi, Keith L Ligon, Patrick Y Wen
Journal: Neuro-Oncology (2021)

Abstract Background Targeted gene NGS testing is available through many academic institutions and commercial entities and is increasingly incorporated in practice guidelines for glioblastoma (GBM). This single-center retrospective study aimed to evaluate the clinical utility of incorporating NGS results in the management of GBM patients at a clinical trials-focused academic center. Methods We identified 1011 consecutive adult patients with pathologically confirmed GBM (IDHwt or IDHmut) who had somatic tumor sequencing (Oncopanel, ~500 cancer gene panel) at DFCI from 2013–2019. Clinical records of all IDHwt GBM patients were reviewed to capture clinical trial enrollment and off-label targeted therapy use based on NGS results. Results Of the 557 IDHwt GBM patients with sequencing, 182 entered clinical trials at diagnosis (32.7%) and 213 (38.2%) entered after recurrence. Sequencing results for 130 patients (23.3%) were utilized for clinical trial enrollment for either targeted therapy indications (6.9 % upfront and 27.7% at recurrent clinical trials and 3.1% for off-label targeted therapy) or exploratory studies (55.4% upfront and 6.9% recurrent clinical trials). Median overall survival was 20.1 months with no survival difference seen between patients enrolled in clinical trials compared to those who were not, in a posthoc analysis. Conclusions While NGS testing has become essential for improved molecular diagnostics, our study illustrates that targeted gene panels remain underutilized for selecting therapy in GBM-IDHwt. Targeted therapy and clinical trial design remain to be improved to help leverage the potential of NGS in clinical care.
Correction: High intensity focused ultrasound: a future alternative to surgery for the treatment of localized pancreatic tumors?
Authors: Martin Fabritius, Thomas Lambin, Elodie Cao, Jade Robert, Laurent Milot, Cyril Lafon, Mathieu Pioche
Journal: Endoscopy (2021)

Correction to: High intensity focused ultrasound: a future alternative to surgery for the treatment of localized pancreatic tumors?Endoscopy 2022; 54(01): E17-E18DOI: 10.1055/a-1338-0293
Abstract 11340: Increasing Mean Arterial Pressure or Cardiac Output in Comatose Out-of-Hospital Cardiac Arrest Patients Undergoing Targeted Temperature Management: Effects on Cerebral Tissue Oxygenation
Authors: Johannes Grand, Sebastian Wiberg, Jesper Kjaergaard, Christian Hassager
Journal: Circulation (2021)

Introduction: There are few data regarding the effects of norepinephrine-uptitration on global and regional hemodynamics in cardiac intensive care patients. Methods: We prospectively studied 10 OHCA patients at our cardiac intensive care unit. The trial consisted of 5 phases. The first 4 phases were achieved by titrating norepinephrine to reach targets of mean arterial pressure (MAP). First a MAP of 65 mmHg, second 75 mmHg, third 85 mmHg, fourth 65 mmHg again. The fifth phase was with a constant MAP of 65 mmHg but aiming at an increased PaCO2 from 6.5-7.3 kPa to increase cardiac output. During each phase, 20 minutes steady state was achieved before measurements. We measured hemodynamic variables with a Swan-Ganz catheter, arterial and mixed venous blood gases, and near-infrared spectroscopy at the forehead (cerebral oxygen saturation). Results: To obtain a MAP at 85 mmHg, norepinephrine was increased from 0.11±0.02 to 0.18±0.02 μg · kg–1 · min–1 (P &lt; 0.001). Norepinephrine uptitration significantly increased MAP, systemic vascular resistance and pulmonary artery pressure, without affecting cardiac output or heart rate. After phase 3, norepinephrine was decreased to basal values, and all variables returned to baseline. Increasing pCO2, resulted in a significant increase in cardiac output and cerebral oxygen saturation, while decreasing systemic vascular resistance. MAP (and NE dose) was unaffected by increasing pCO2. Conclusions: A short-term increase in MAP with norepinephrine in resuscitated OHCA-patients is associated with increased SVR and PVR without affecting cardiac output or NIRS of the brain. An increase in CO caused by an increase in pCO2 and thereby a decreased SVR increased NIRS potentially improving brain oxygenation.
Covid-19: Second judge says that “most complex covid patient in the world” should be allowed to die
Authors: Clare Dyer
Journal: BMJ (2021)

Covid-19: Second judge says that "most complex covid patient in the world" should be allowed to die Clare DyerA 56 year old woman described by doctors as "the most complex covid patient in the world" should have ventilation withdrawn and be allowed to die, a second High Court judge has ruled after her family successfully appealed against the original decision.The burdens of the treatment, including painful suctioning every two to three hours, outweigh the benefits of her life, Mrs Justice Theis concluded.2
Qualitative Research Methods in Chronic Disease: Introduction and Opportunities to Promote Health Equity
Authors: Rachel C. Shelton, Morgan M. Philbin, Shoba Ramanadhan
Journal: Annual Review of Public Health (2021)

Public health research that addresses chronic disease has historically underutilized and undervalued qualitative methods. This has limited the field's ability to advance (a) a more in-depth understanding of the factors and processes that shape health behaviors, (b) contextualized explanations of interventions' impacts (e.g., why and how something did or did not work for recipients and systems), and (c) opportunities for building and testing theories. We introduce frameworks and methodological approaches common to qualitative research, discuss how and when to apply them in order to advance health equity, and highlight relevant strengths and challenges. We provide an overview of data collection, sampling, and analysis for qualitative research, and we describe research questions that can be addressed by applying qualitative methods across the continuum of chronic disease research. Finally, we offer recommendations to promote the strategic application of rigorous qualitative methods, with an emphasis on priority areas to enhance health equity across the evidence generation continuum.
The adjuvanted recombinant zoster vaccine co-administered with the 13-valent pneumococcal conjugate vaccine in adults aged ≥50 years: A randomized trial
Authors: Ji-Young Min, Agnes Mwakingwe-Omari, Megan Riley, Lifeter Yenwo Molo, Jyoti Soni, Ginette Girard, Jasur Danier
Journal: Journal of Infection (2021)

Herpes zoster (HZ) results from reactivation of latent varicella-zoster virus. Adults at increased risk of HZ (due to immunocompromising conditions or older age) are also at risk of pneumococcal disease, both of which are preventable by vaccination. We evaluated simultaneous versus sequential administration of the adjuvanted recombinant zoster vaccine (RZV) and the 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged ≥50 years.In this phase IIIB multinational trial (NCT03439657), participants were randomized 1:1 to receive either the first RZV dose and PCV13 simultaneously followed by the second RZV dose two months later (Co-Ad, N = 449), or at two-month intervals, PCV13, the first RZV dose, and the second RZV dose sequentially (Control, N = 463). Objectives were to demonstrate that immune responses to both vaccines are non-inferior when co-administered compared to sequential administration and to evaluate the safety of their co-administration.The RZV vaccine response rate (VRR) in the Co-Ad group was 99.1% (95% confidence interval [CI]: 97.6-99.7), meeting the VRR success criterion. Non-inferiority criteria for the Co-Ad versus Control group were also met for anti-glycoprotein E antibodies (adjusted geometric mean concentration Control/Co-Ad ratio 1.07 [95%CI: 0.99-1.16]) and all PCV13 serotypes (adjusted antibody geometric mean titer Control/Co-Ad ratios 1.02 [95%CI: 0.86-1.22] to 1.36 [95%CI: 1.07-1.73]). Upon co-administration, the frequency of solicited local adverse events was consistent with the known safety profile of each individual vaccine, whereas solicited general adverse events were within the same range as for RZV alone.RZV co-administered with PCV13 had an acceptable safety profile. Humoral immune responses to both vaccines were non-inferior when co-administered compared to sequential administration. These results suggest that adults may benefit from receiving RZV and a PCV at the same healthcare visit.
The role of nanoparticle format and route of administration on self-amplifying mRNA vaccine potency
Authors: Giulia Anderluzzi, Gustavo Lou, Stuart Woods, Signe Tandrup Schmidt, Simona Gallorini, Michela Brazzoli, Russell Johnson, Craig W. Roberts, Derek T. O'Hagan, Barbara C. Baudner, Yvonne Perrie
Journal: Journal of Controlled Release (2021)