Search

Croissant de Garengeot's hernia is defined as the presence of an appendix in the femoral hernial sac. It is rare and occurs mostly in females. We report this hernia in a male patient along with the surgical management and review of literature. [ABSTRACT FROM AUTHOR]

Gastrointestinal metastasis of the breast cancer is rare and its management varies significantly from that of a primary bowel cancer. We report a case of invasive ductal cancer metastasizing to the rectum and masquerading as a rectal primary.A 60 year old caucasian woman presented with fresh rectal bleeding nine years after treatment of her primary breast cancer. The investigations revealed features suggestive of primary rectal malignancy and was managed accordingly. However, the surgical histopathology revealed poorly differentiated metastatic adenocarcinoma and the immunohistochemical evaluation confirmed origin from a breast primary. She had an uneventful post-operative recovery and remains disease free thus far.The continuing advancement in the management of breast cancer patients with resulting increase in the overall survival will lead to such unusual metastatic presentations. Hence, the awareness, identification and differentiation of such rare metastatic presentation are important in order to manage the patients appropriately in the future. [ABSTRACT FROM PUBLISHER]

Introduction: Biologic disease-modifying antirheumatic drugs (bDMARD) are often discontinued when a patient with rheumatoid arthritis (RA) is diagnosed with cancer. Our aim was to determine trends in bDMARD utilization in patients with RA and recently diagnosed cancer., Method: We examined two national claims databases to identify adults with RA and recently diagnosed colorectal, lung, or prostate cancer (Optum's de-identified Clinformatics® Data Mart Database 2008-2022, and Surveillance, Epidemiology, and End Results Program (SEER) Medicare-linked 2008-2017). We determined time trends in bDMARD and tumor necrosis factor inhibitor (TNFi) prescriptions during the first 3 years after cancer with Cochram-Armitage tests and multivariable logistic regression. Cancer cohorts were analyzed separately., Results: We included 3595 patients in all six cohorts (in Clinformatics® 503 with colorectal, 468 with lung, and 440 with prostate cancer; in SEER-Medicare 580 with colorectal, 1010 with lung, and 594 with prostate cancer). No significant increase was observed in bDMARD or TNFi utilization over time. Overall, use of bDMARD within the first 3 years of follow-up ranged from 16.7% (Clinformatics® lung cohort) to 29.7% (SEER-Medicare colorectal cohort). The major predictor of bDMARD utilization was prior use in the 3 months before cancer diagnosis (p < 0.001 for all cancers) and earlier cancer stage (p < 0.001 in colorectal and lung cancer and p = 0.05 in prostate cancer)., Conclusions: Use of bDMARD in patients with RA and recently diagnosed common cancers has not increased since 2008. Additional evidence on the safety of bDMARD in patients with early cancer is needed to ensure appropriate management of their RA. Key Points • Use of bDMARD and TNFi in patients with RA and early colorectal, lung, or prostate cancer has been stable since 2008, with no significant increases over time. • The major determinant of receiving bDMARD after cancer diagnosis was prior treatment with bDMARD in the prior 3 months before cancer. • Patients with advanced cancer stage and distant metastases were less likely to receive bDMARD and TNFi than those at early stages of disease., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: There have been concerns about the use of tumor necrosis factor inhibitors (TNFi) for autoimmune disease in patients with recently diagnosed cancer. We assessed the survival of patients with rheumatoid arthritis (RA) and newly diagnosed early breast cancer (BC) treated with TNFi in the first two years after BC diagnosis., Methods: We identified patients in two datasets: (1) Optum's de-identified Clinformatics ® Data Mart Database (CDM), (2) Surveillance, Epidemiology, and End Results program (SEER) and Texas Cancer Registry (TCR) Medicare-linked cohort. We grouped patients according to whether they received TNFi, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) only, or no DMARDs within 2 years after BC. Outcomes were overall survival (OS) and BC-specific survival (BCSS). We conducted landmark analyses at years 1 and 2, with multivariable Cox regressions using propensity scores for adjustment., Results: In the first year after BC, 165/970 (17.0%) and 201/1246 (16.1%) patients received TNFi in CDM and SEER/TCR-Medicare respectively. In the 1 year landmark, no significant differences in OS were observed between patients treated with TNFi and patients treated with csDMARDs only in CDM (hazard ratio [HR] = 0.77, 95% confidence interval [CI] 0.42-1.40) or SEER/TCR-Medicare (HR = 0.84, 95% CI 0.54-1.31). BCSS (SEER/TCR-Medicare) was better in patients receiving TNFi than in those receiving csDMARDs only (HR = 0.28, 95% CI 0.08-0.98). In CDM, glucocorticoid therapy had worse OS than those without glucocorticoids (HR = 2.18, 95% CI 1.13-4.18). This was also observed in SEER/TCR-Medicare (not statistically significant). Similar results were observed for the 2 year landmark., Conclusions: TNFi treatment during the first two years after early BC was not associated with worse survival., (© 2024. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Internalized stigma, also known as self-stigma, is negatively associated with a person's willingness to seek mental health services and follow their treatment plan. This can hinder a person's recovery, exacerbate their mental health illnesses, and reduce their quality of life. A primary directive of the Veteran Affairs Psychosocial Rehabilitation and Recovery Center (PRRC) program is to help veterans overcome their internalized stigma. This study is the first to evaluate the association between receiving PRRC services over time and veteran reported levels of internalized stigma based on Internalized Stigma of Mental Illness-Brief-10 scores using longitudinal PRRC Forms Data. The analysis was performed using a random-effects ordered logistic regression adjusting for veteran sociodemographic and clinical characteristics. Our study cohort consisted of 2,774 veterans who received PRRC services between fiscal years 2018 and 2021 and who had an intake form at the start of the PRRC service and at least one follow-up form. Our study found that veterans had lower odds of having a higher level of internalized stigma at the first follow-up relative to their intake ( OR : 0.80; 95% CI [0.70, 0.92]), and these odds continued to decrease with each subsequent follow-up. These results potentially indicate the effectiveness of the PRRC program in reducing levels of internalized stigma among the veterans. Our study also suggests the need for greater clinical attention and resources for subgroups such as older veterans, male veterans, and veterans with posttraumatic stress disorder, anxiety, or personality disorders, who reported higher levels of internalized stigma. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Objective: Biologic disease-modifying antirheumatic drugs (bDMARDs) are immunosuppressants, and there have been concerns that they might impact tumor immunity in patients with cancer with rheumatoid arthritis (RA). The purpose of this study was to describe the utilization trends of bDMARD in patients with RA after breast cancer (BC) diagnosis., Methods: We performed a retrospective cohort study of adults with RA and BC (2008 onward) from Optum's de-identified Clinformatics® Data Mart Database (CDM); the Surveillance, Epidemiology, and End Results Program (SEER) Medicare; and the Texas Cancer Registry (TCR) Medicare databases. We evaluated bDMARD utilization trends during the first three years after BC. We conducted multivariable logistic regression to evaluate the association of utilization with patient characteristics., Results: A total 1,412 patients were identified in CDM and 1,439 patients in SEER/TCR-Medicare. During the three months before BC diagnosis, 28.2% (CDM) and 26.9% (SEER/TCR-Medicare) patients had received bDMARDs. Within the first three years after diagnosis, 24.1% (CDM) and 26.4% (SEER/TCR-Medicare) were receiving bDMARDs. About 70% of the patients in the two cohorts received glucocorticoids with no significant time trend increases. The largest predictor of bDMARD utilization was prior use before BC (CDM: odds ratio [OR] 27.15, 95% confidence interval [CI] 19.29-38.19; SEER/TCR: OR 18.98, 95% CI 13.72-26.26). Regional and distant BC compared to in situ or localized were also associated with lower bDMARDs utilization in SEER/TCR-Medicare (OR 0.54, 95% CI 0.36-0.82; OR 0.31, 95% CI 0.13-0.77, respectively)., Conclusion: The utilization of tumor necrosis factor inhibitors and other bDMARDs in patients with RA and recent BC has not increased since 2008. Glucocorticoids utilization remained high. The largest predictor of bDMARD utilization was prior use before BC., (© 2024 American College of Rheumatology.)

Importance: Lack of timely follow-up of cancer-related abnormal test results can lead to delayed or missed diagnoses, adverse cancer outcomes, and substantial cost burden for patients. Care delivery models, such as the Veterans Affairs' (VA) Patient-Aligned Care Team (PACT), which aim to improve patient-centered care coordination, could potentially also improve timely follow-up of abnormal test results. PACT was implemented nationally in the VA between 2010 and 2012., Objective: To evaluate the long-term association between PACT implementation and timely follow-up of abnormal test results related to the diagnosis of 5 different cancers., Design, Setting, and Participants: This multiyear retrospective cohort study used 14 years of VA data (2006-2019), which were analyzed using panel data-based random-effects linear regressions. The setting included all VA clinics and facilities. The participants were adult patients who underwent diagnostic testing related to 5 different cancers and had abnormal test results. Data extraction and statistical analyses were performed from September 2021 to December 2023., Exposure: Calendar years denoting preperiods and postperiods of PACT implementation, and the PACT Implementation Progress Index Score denoting the extent of implementation in each VA clinic and facility., Main Outcome and Measure: Percentage of potentially missed timely follow-ups of abnormal test results., Results: This study analyzed 6 data sets representing 5 different types of cancers. During the initial years of PACT implementation (2010 to 2013), percentage of potentially missed timely follow-ups decreased between 3 to 7 percentage points for urinalysis suggestive of bladder cancer, 12 to 14 percentage points for mammograms suggestive of breast cancer, 19 to 22 percentage points for fecal tests suggestive of colorectal cancer, and 6 to 13 percentage points for iron deficiency anemia laboratory tests suggestive of colorectal cancer, with no statistically significant changes for α-fetoprotien tests and lung cancer imaging. However, these beneficial reductions were not sustained over time. Better PACT implementation scores were associated with a decrease in potentially missed timely follow-up percentages for urinalysis (0.3-percentage point reduction [95% CI, -0.6 to -0.1] with 1-point increase in the score), and laboratory tests suggestive of iron deficiency anemia (0.5-percentage point reduction [95% CI,-0.8 to -0.2] with 1-point increase in the score)., Conclusions and Relevance: This cohort study found that implementation of PACT in the VA was associated with a potential short-term improvement in the quality of follow-up for certain test results. Additional multifaceted sustained interventions to reduce missed test results are required to prevent care delays.

Objective: This study was undertaken to examine averted stroke in optimized stroke systems., Methods: This secondary analysis of a multicenter trial from 2014 to 2020 compared patients treated by mobile stroke unit (MSU) versus standard management. The analytical cohort consisted of participants with suspected stroke treated with intravenous thrombolysis. The main outcome was a tissue-defined averted stroke, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours attributed to thrombolysis and no acute infarction/hemorrhage on imaging. An additional outcome was stroke with early symptom resolution, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours attributed to thrombolysis., Results: Among 1,009 patients with a median last known well to thrombolysis time of 87 minutes, 159 (16%) had tissue-defined averted stroke and 276 (27%) had stroke with early symptom resolution. Compared with standard management, MSU care was associated with more tissue-defined averted stroke (18% vs 11%, adjusted odds ratio [aOR] = 1.82, 95% confidence interval [CI] = 1.13-2.98) and stroke with early symptom resolution (31% vs 21%, aOR = 1.74, 95% CI = 1.12-2.61). The relationships between thrombolysis treatment time and averted/early recovered stroke appeared nonlinear. Most models indicated increased odds for stroke with early symptom resolution but not tissue-defined averted stroke with earlier treatment. Additionally, younger age, female gender, hyperlipidemia, lower National Institutes of Health Stroke Scale, lower blood pressure, and no large vessel occlusion were associated with both tissue-defined averted stroke and stroke with early symptom resolution., Interpretation: In optimized stroke systems, 1 in 4 patients treated with thrombolysis recovered within 24 hours and 1 in 6 had no demonstrable brain injury on imaging. ANN NEUROL 2024;95:347-361., (© 2023 American Neurological Association.)

Cancer presents a formidable challenge, necessitating innovative therapies that maximize effectiveness while minimizing harm to healthy tissues. Nanotechnology has emerged as a transformative force in cancer treatment, particularly through nano-enabled photodynamic therapy (NE-PDT), which leverages precise and targeted interventions. NE-PDT capitalizes on photosensitizers activated by light to generate reactive oxygen species (ROS) that initiate apoptotic pathways in cancer cells. Nanoparticle enhancements optimize this process, improving drug delivery, selectivity, and ROS production within tumors. This review dissects NE-PDT's mechanistic framework, showcasing its potential to harness apoptosis as a potent tool in cancer therapy. Furthermore, the review explores the synergy between NE-PDT and complementary treatments like chemotherapy, immunotherapy, and targeted therapies, highlighting the potential to amplify apoptotic responses, enhance immune recognition of cancer cells, and inhibit resistance mechanisms. Preclinical and clinical advancements in NE-PDT demonstrate its efficacy across various cancer types. Challenges in translating NE-PDT into clinical practice are also addressed, emphasizing the need for optimizing nanoparticle design, refining dosimetry, and ensuring long-term safety. Ultimately, NE-PDT represents a promising approach in cancer therapy, utilizing the intricate mechanisms of apoptosis to address therapeutic hurdles. The review underscores the importance of understanding the interplay between nanoparticles, ROS generation, and apoptotic pathways, contributing to a deeper comprehension of cancer biology and novel therapeutic strategies. As interdisciplinary collaborations continue to thrive, NE-PDT offers hope for effective and targeted cancer interventions, where apoptosis manipulation becomes central to conquering cancer. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease., (© 2024 The Authors. WIREs Nanomedicine and Nanobiotechnology published by Wiley Periodicals LLC.)

Objective: To enhance RF safety when implantable medical devices are located within the body coil but outside the imaging region by using a secondary resonator (SR) to reduce electric fields, the corresponding specific absorption rate (SAR), and temperature change during MRI., Materials and Methods: This study was conducted using numerical simulations with an American Society for Testing and Materials (ASTM) phantom and adult human models of Ella and Duke from Virtual Family Models, along with corresponding experimental results of temperature change obtained using the ASTM phantom. The circular SR was designed with an inner diameter of 150 mm and a width of 6 mm. Experimental measurements were carried out using a 3 T Medical Implant Test System (MITS) body coil, electromagnetic (EM) field mapping probes, and an ASTM phantom., Results: The magnitudes of B 1 + (|B 1 + |) and SAR 1g were reduced by 15.2% and 5.85% within the volume of interest (VoI) of an ASTM phantom, when a SR that generates opposing electromagnetic fields was utilized. Likewise, the Δ|B 1 + | and ΔSAR 1g were reduced by up to 56.7% and 57.5% within the VoI of an Ella model containing a copper rod when an opposing SR was used., Conclusion: A novel method employing the designed SR, which generates opposing magnetic fields to partially shield a sample, has been proposed to mitigate the risk of induced-RF heating at the VoI through numerical simulations and corresponding experiments under various conditions at 3.0 T., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Few data exist on acute stroke treatment in patients with pre-existing disability (PD) since they are usually excluded from clinical trials. A recent trial of mobile stroke units (MSUs) demonstrated faster treatment and improved outcomes, and included PD patients., Aim: To determine outcomes with tissue plasminogen activator (tPA), and benefit of MSU versus management by emergency medical services (EMS), for PD patients., Methods: Primary outcomes were utility-weighted modified Rankin Scale (uw-mRS). Linear and logistic regression models compared outcomes in patients with versus without PD, and PD patients treated by MSU versus standard management by EMS. Time metrics, safety, quality of life, and health-care utilization were compared., Results: Of the 1047 tPA-eligible ischemic stroke patients, 254 were with PD (baseline mRS 2-5) and 793 were without PD (baseline mRS 0-1). Although PD patients had worse 90-day uw-mRS, higher mortality, more health-care utilization, and worse quality of life than non-disabled patients, 53% returned to at least their baseline mRS, those treated faster had better outcome, and there was no increased bleeding risk. Comparing PD patients treated by MSU versus EMS, 90-day uw-mRS was 0.42 versus 0.36 (p = 0.07) and 57% versus 46% returned to at least their baseline mRS. There was no interaction between disability status and MSU versus EMS group assignment (p = 0.67) for 90-day uw-mRS., Conclusion: PD did not prevent the benefit of faster treatment with tPA in the BEST-MSU study. Our data support inclusion of PD patients in the MSU management paradigm., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.C. Grotta has received grants from Patient-Centered Outcomes Research Institute (PCORI), NIH, Genentech, CSL Behring, and Chiesi; is a consultant for Frazer, advison the scientific advisory board for Haemonetics and Acticor, and on the DSMB for Prolong Pharma. J.L. Saver receives contracted hourly payments from Bayer, Biogen, Roche, Genentech, Medtronic, Novo Nordisk, and Occlutech for service on clinical trial steering committees and DSMBs. The remaining authors have no disclosures.

Importance: The comorbidity network represents multiple diseases and their relationships in a graph. Understanding comorbidity networks among critical care unit (CCU) patients can help doctors diagnose patients faster, minimize missed diagnoses, and potentially decrease morbidity and mortality., Objective: The main objective of this study was to identify the comorbidity network among CCU patients using a novel application of a machine learning method (graphical modeling method). The second objective was to compare the machine learning method with a traditional pairwise method in simulation., Method: This cross-sectional study used CCU patients' data from Medical Information Mart for the Intensive Care-3 (MIMIC-3) dataset, an electronic health record (EHR) of patients with CCU hospitalizations within Beth Israel Deaconess Hospital from 2001 to 2012. A machine learning method (graphical modeling method) was applied to identify the comorbidity network of 654 diagnosis categories among 46,511 patients., Results: Out of the 654 diagnosis categories, the graphical modeling method identified a comorbidity network of 2,806 associations in 510 diagnosis categories. Two medical professionals reviewed the comorbidity network and confirmed that the associations were consistent with current medical understanding. Moreover, the strongest association in our network was between "poisoning by psychotropic agents" and "accidental poisoning by tranquilizers" (logOR 8.16), and the most connected diagnosis was "disorders of fluid, electrolyte, and acid-base balance" (63 associated diagnosis categories). Our method outperformed traditional pairwise comorbidity network methods in simulation studies. Some strongest associations between diagnosis categories were also identified, for example, "diagnoses of mitral and aortic valve" and "other rheumatic heart disease" (logOR: 5.15). Furthermore, our method identified diagnosis categories that were connected with most other diagnosis categories, for example, "disorders of fluid, electrolyte, and acid-base balance" was associated with 63 other diagnosis categories. Additionally, using a data-driven approach, our method partitioned the diagnosis categories into 14 modularity classes., Conclusion and Relevance: Our graphical modeling method inferred a logical comorbidity network whose associations were consistent with current medical understanding and outperformed traditional network methods in simulation. Our comorbidity network method can potentially assist CCU doctors in diagnosing patients faster and minimizing missed diagnoses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Huepenbecker, Zhu, Rajan, Fujimoto and Luo.)

Objective: The intensity of an antibiotic stewardship intervention to achieve clinical impact is not known. We conducted a multisite dissemination project of an intervention to reduce treatment of asymptomatic bacteriuria (ASB) and studied: (1) the association between implementation metrics and clinical outcomes and (2) the cost of implementation., Design/setting/participants: A central site facilitated a multimodality intervention to decrease unnecessary urine cultures and antibiotic treatment in patients with ASB at 4 Veterans Affairs medical centers., Methods: The intervention consisted of a decision support aid algorithm and interactive teaching cases that provided in the moment audit and feedback on how to manage ASB. Implementation outcomes included minutes spent in intervention delivery, number of healthcare professionals reached, and number of sessions delivered. Clinical outcomes included days of antibiotic therapy (DOT), length of antibiotic therapy (LOT), and number of urine cultures ordered per 1000 bed days. Personnel reported weekly time logs., Results: Minutes spent in intervention delivery were inversely correlated with two clinical outcomes, DOT ( R -0.3, P = .04) and LOT ( R -0.3, P = .02). Number of healthcare professionals reached and number of sessions delivered were not correlated with clinical outcomes of DOT ( R -0.003, P = .98, R = -0.059, P = .69) or LOT ( R +0.073, P = .62, R -0.102, P = .49). Physician champions spent an average of 3.8% of effort on the intervention. The implementation cost was USD 22,299/year per site on average., Conclusions: The amount of time local teams spent in delivery of an antibiotic stewardship intervention was correlated with the desired decrease in antibiotic use. Implementing this successful antibiotic stewardship intervention required minimal time., Competing Interests: No authors report conflict of interest., (© The Author(s) 2023.)

Background: Research on risk factors for neuropsychiatric adverse events (NAEs) in smoking cessation with pharmacotherapy is scarce. We aimed to identify predictors and develop a prediction model for risk of NAEs in smoking cessation with medications using Bayesian regularization., Methods: Bayesian regularization was implemented by applying two shrinkage priors, Horseshoe and Laplace, to generalized linear mixed models on data from 1203 patients treated with nicotine patch, varenicline or placebo. Two predictor models were considered to separate summary scores and item scores in the psychosocial instruments. The summary score model had 19 predictors or 26 dummy variables and the item score model 51 predictors or 58 dummy variables. A total of 18 models were investigated., Results: An item score model with Horseshoe prior and 7 degrees of freedom was selected as the final model upon model comparison and assessment. At baseline, smokers reporting more abnormal dreams or nightmares had 16% greater odds of experiencing NAEs during treatment (regularized odds ratio (rOR) = 1.16, 95% credible interval (CrI) = 0.95 - 1.56, posterior probability P(rOR > 1) = 0.90) while those with more severe sleep problems had 9% greater odds (rOR = 1.09, 95% CrI = 0.95 - 1.37, P(rOR > 1) = 0.85). The prouder a person felt one week before baseline resulted in 13% smaller odds of having NAEs (rOR = 0.87, 95% CrI = 0.71 - 1.02, P(rOR < 1) = 0.94). Odds of NAEs were comparable across treatment groups. The final model did not perform well in the test set., Conclusions: Worse sleep-related symptoms reported at baseline resulted in 85%-90% probability of being more likely to experience NAEs during smoking cessation with pharmacotherapy. Treatment for sleep disturbance should be incorporated in smoking cessation program for smokers with sleep disturbance at baseline. Bayesian regularization with Horseshoe prior permits including more predictors in a regression model when there is a low number of events per variable., (© 2023. The Author(s).)

The purpose of this study is to examine the geographical patterns of adjuvant hormonal therapy adherence and persistence and the associated factors in insured Texan women aged 18-64 with early breast cancer. A retrospective cohort study was conducted using 5-year claims data for the population insured by the Blue Cross Blue Shield of Texas (BCBSTX). Women diagnosed with early breast cancer who were taking tamoxifen or aromatase inhibitors (AIs) for adjuvant hormonal therapy with at least one prescription claim were identified. Adherence to adjuvant hormonal therapy and persistence with adjuvant hormonal therapy were calculated as outcome measures. Women without a gap between two consecutively dispensed prescriptions of at least 90 days were considered to be persistently taking the medications. Patient-level multivariate logistic regression models with repeated regional-level adjustments and a Cox proportional hazards model with mixed effects were used to determine the geographical variations and patient-, provider-, and area-level factors that were associated with adjuvant hormonal therapy adherence and persistence. Of the 938 women in the cohort, 627 (66.8%) initiated adjuvant hormonal therapy. Most of the smaller HRRs have significantly higher or lower rates of treatment adherence and persistence rates relative to the median regions. The use of AHT varies substantially from one geographical area to another, especially for adherence, with an approximately two-fold difference between the lowest and highest areas, and area-level factors were found to be significantly associated with the compliance of AHT. There are geographical variations in AHT adherence and persistence in Texas. Patient-level and area-level factors have significant associations explaining these patterns.

Accumulation of aggregated and misfolded proteins, leading to endoplasmic reticulum stress and activation of the unfolded protein response, is a hallmark of several neurodegenerative disorders, including Alzheimer's and Parkinson's disease. Genetic screens are powerful tools that are proving invaluable in identifying novel modulators of disease associated processes. Here, we performed a loss-of-function genetic screen using a human druggable genome library, followed by an arrayed-screen validation, in human iPSC-derived cortical neurons. We identified and genetically validated 13 genes, whose knockout was neuroprotective against Tunicamycin, a glycoprotein synthesis inhibitor widely used to induce endoplasmic reticulum stress. We also demonstrated that pharmacological inhibition of KAT2B, a lysine acetyltransferase identified by our genetic screens, by L-Moses, attenuates Tunicamycin-mediated neuronal cell death and activation of CHOP, a key pro-apoptotic member of the unfolded protein response in both cortical and dopaminergic neurons. Follow-up transcriptional analysis suggested that L-Moses provided neuroprotection by partly reversing the transcriptional changes caused by Tunicamycin. Finally, L-Moses treatment attenuated total protein levels affected by Tunicamycin, without affecting their acetylation profile. In summary, using an unbiased approach, we identified KAT2B and its inhibitor, L-Moses, as potential therapeutic targets for neurodegenerative diseases., (© 2023. The Author(s).)

This study aims to characterize a new Ti-25Ta-25Nb-5Sn alloy for biomedical application. Microstructure, phase formation, mechanical and corrosion properties, along with the cell culture study of the Ti-25Ta-25Nb alloy with Sn content 5 mass% are presented in this article. The experimental alloy was processed in an arc melting furnace, cold worked, and heat treated. For characterization, optical microscopy, X-ray diffraction, microhardness, and Young's modulus measurements were employed. Corrosion behavior was also evaluated using open-circuit potential (OCP) and potentiodynamic polarization. In vitro studies with human ADSCs were performed to investigate cell viability, adhesion, proliferation, and differentiation. Comparison among the mechanical properties observed in other metal alloy systems, including CP Ti, Ti-25Ta-25Nb, and Ti-25Ta-25-Nb-3Sn showed an increase in microhardness and a decrease in the Young's modulus when compared to CP Ti. The potentiodynamic polarization tests indicated that the corrosion resistance of the Ti-25Ta-25Nb-5Sn alloy was similar to CP Ti and the experiments in vitro demonstrated great interactions between the alloy surface and cells in terms of adhesion, proliferation, and differentiation. Therefore, this alloy presents potential for biomedical applications with properties required for good performance.

Background: Treatment of patients with acute ischemic stroke on mobile stroke units (MSUs) improves outcomes compared with management by standard emergency medical services ambulances and is associated with more patients treated with intravenous tPA (tissue-type plasminogen activator) in the first golden hour after last known normal. We explored the predictors and outcomes of first-hour treatment (FHT) compared with later treatment in an alternating-week cluster-controlled trial of MSUs., Methods: We analyzed all patients treated with intravenous tPA in the BEST-MSU Study (Benefits of Stroke Treatment Delivered by a Mobile Stroke Unit Compared to Standard Management by Emergency Medical Services). After stratifying by treatment timeframe, we identified factors associated with FHT. We performed adjusted analyses of the association between FHT and clinical outcome and modeled the shape of the relationship between last known normal-to-treatment time and excellent outcome., Results: Among 941 tPA-treated patients, 206 (21.8%) had lytic started within 60 minutes. Treatment on the MSU, older age, male sex, alert by 911, faster arrival on-scene and imaging, more severe stroke, atrial fibrillation, and absence of heart failure and pretreatment antihypertensive treatment were associated with FHT. Compared with later treatment, FHT was associated with higher adjusted odds ratio for 90-day modified Rankin Scale score of 0 to 1 (odds ratio, 1.87 [95% CI, 1.25-2.84]; P =0.003). Among FHT patients, 68% achieved a 90-day modified Rankin Scale of 0 or 1 or returned to their baseline status. FHT was not associated with higher risk of hemorrhage and was associated with reduced risk of treating neurovascular mimics., Conclusions: FHT almost doubles the odds of excellent clinical outcome without increased risk compared with later treatment, which supports the use of MSUs.

The Peace of Mind Program is an evidence-based intervention to improve mammography appointment adherence in underserved women. The aim of this study was to assess effectiveness of the intervention and implementation of the intervention in safety net clinics. The intervention was implemented through a non-randomized stepped wedge cluster hybrid study design with 19 Federally Qualified Health Centers and charity care clinics within the Greater Houston area. A multivariable generalized estimating equation logistic regression was conducted to examine mammography appointment adherence. A survey assessing Consolidated Framework for Implementation Research constructs was also conducted with clinic staff prior to adoption and eight weeks post implementation. One-sided t-tests were conducted to analyze mean score changes between the surveys. A total of 4402 women (baseline period = 2078; intervention period = 2324) were included in the final regression analysis. Women in the intervention period were more likely to attend or reschedule their mammography appointment (OR = 1.30; p < 0.01) than those in the baseline period receiving usual care. Women who completed the intervention were more likely to attend or reschedule their mammography appointment than those who did not complete the intervention (OR = 1.62; p < 0.01). The mammography appointment no-show rates for those in the baseline period, in the intervention period, and who completed the intervention were, respectively, 22%, 19%, and 15%. A total of 15 clinics prior to adoption and eight clinics completed the survey at 8 weeks post implementation A statistically significant mean score decrease was observed in Inner Setting and in two Inner Setting CFIR constructs, Culture-Effort, and Implementation Climate. While the intervention improved mammography appointment adherence, there are opportunities to further integrate Consolidated Framework for Implementation Research constructs. Trial registration: Clinical trials registration number: NCT02296177., (© 2021. The Author(s).)

Background: Hematoma enlargement (HE) after intracerebral hemorrhage (ICH) is a therapeutic target for improving outcomes. Hemostatic therapies to prevent HE may be more effective the earlier they are attempted. An understanding of HE in first 1 to 2 hours specifically in the prehospital setting would help guide future treatment interventions in this time frame and setting., Methods: Patients with spontaneous ICH within 4 hours of symptom onset were prospectively evaluated between May 2014 and April 2020 as a prespecified substudy within a multicenter trial of prehospital mobile stroke unit versus standard management. Baseline computed tomography scans obtained <1, 1 to 2, and 2 to 4 hours postsymptom onset on the mobile stroke unit in the prehospital setting were compared with computed tomography scans repeated 1 hour later and at 24 hours in the hospital. HE was defined as >6 mL if baseline ICH volume was < 20 mL and 33% increase if baseline volume >20 mL. The association between time from symptom onset to baseline computed tomography (hours) and HE was investigated using Wilcoxon rank-sum test when time was treated as a continuous variable and using Fisher exact test when time was categorized. Kruskal-Wallis and Wilcoxon rank-sum tests evaluated differences in baseline volumes and HE. Univariable and multivariable logistic regression analyses were conducted to identify factors associated with HE and variable selection was performed using cross-validated L1-regularized (Lasso regression). This study adhered to STROBE guidelines (Strengthening the Reporting of Observational Studies in Epidemiology) for cohort studies., Results: One hundred thirty-nine patients were included. There was no difference between baseline ICH volumes obtained <1 hour (n=43) versus 1 to 2 hour (n=51) versus >2 hours (n=45) from symptom onset (median [interquartile range], 13 mL [6-24] versus 14 mL [6-30] versus 12 mL [4-19]; P =0.65). However, within the same 3 time epochs, initial hematoma growth (volume/time from onset) was greater with earlier baseline scanning (median [interquartile range], 17 mL/hour [9-35] versus 9 mL/hour [5-23]) versus 4 mL/hour [2-7]; P <0.001). Forty-nine patients had repeat scans 1 hour after baseline imaging (median, 2.3 hours [interquartile range. 1.9-3.1] after symptom onset). Eight patients (16%) had HE during that 1-hour interval; all of these occurred in patients with baseline imaging within 2 hours of onset (5/18=28% with baseline imaging within 1 hour, 3/18=17% within 1-2 hour, 0/13=0% >2 hours; P =0.02). HE did not occur between the scans repeated at 1 hour and 24 hours. No association between baseline variables and HE was detected in multivariable analyses., Conclusions: HE in the next hour occurs in 28% of ICH patients with baseline imaging within the first hour after symptom onset, and in 17% of those with baseline imaging between 1 and 2 hours. These patients would be a target for ultraearly hemostatic intervention.

Importance: Type 2 diabetes is a prevalent and morbid condition. Poor engagement with self-management can contribute to diabetes-associated distress and hinder diabetes control., Objective: To evaluate the implementation and effectiveness of Empowering Patients in Chronic Care (EPICC), an evidence-based intervention to improve diabetes-associated distress and hemoglobin A1c (HbA1c) levels after the intervention and after 6-month maintenance., Design, Setting, and Participants: This hybrid (implementation-effectiveness) randomized clinical trial was performed in Veterans Affairs clinics across Illinois, Indiana, and Texas from July 1, 2015, to June 30, 2017. Participants included adults with uncontrolled type 2 diabetes (HbA1c level >8.0%) who received primary care during the prior year in participating clinics. Data collection was completed on November 30, 2018, and data analysis was completed on June 30, 2020. All analyses were based on intention to treat., Interventions: Participants in EPICC attended 6 group sessions based on a collaborative goal-setting theory led by health care professionals. Clinicians conducted individual motivational interviewing sessions after each group. Usual care was enhanced (EUC) with diabetes education., Main Outcomes and Measures: The primary outcome consisted of changes in HbA1c levels after the intervention and during maintenance. Secondary outcomes included the Diabetes Distress Scale (DDS), Morisky Medication Adherence Scale, and Lorig Self-efficacy Scale. Secondary implementation outcomes included reach, adoption, and implementation (number of sessions attended per patient)., Results: A total of 280 participants with type 2 diabetes (mean [SD] age, 67.2 [8.4] years; 264 men [94.3]; 134 non-Hispanic White individuals [47.9%]) were equally randomized to EPICC or EUC. Participants receiving EPICC had significant postintervention improvements in HbA1c levels (F1, 252 = 9.12, Cohen d = 0.36 [95% CI, 0.12-0.59]; P = .003) and DDS (F1, 245 = 9.06, Cohen d = 0.37 [95% CI, 0.13-0.60]; P = .003) compared with EUC. During maintenance, differences between the EUC and EPICC groups remained significant for DDS score (F1, 245 = 8.94, Cohen d = 0.36 [95% CI, 0.12-0.59]; P = .003) but not for HbA1c levels (F1, 252 = 0.29, Cohen d = 0.06 [95% CI, -0.17 to 0.30]; P = .60). Improvements in DDS scores were modest. There were no differences between EPICC and EUC in improvements after intervention or maintenance for either adherence or self-efficacy. Among all 4002 eligible patients, 280 (7.0%) enrolled in the study (reach). Each clinic conducted all planned EPICC sessions and cohorts (100% adoption). The EPICC group participants attended a mean (SD) of 4.34 (1.98) sessions, with 54 (38.6%) receiving all 6 sessions., Conclusions and Relevance: A patient-empowerment approach using longitudinal collaborative goal setting and motivational interviewing is feasible in primary care. Improvements in HbA1c levels after the intervention were not sustained after maintenance. Modest improvements in diabetes-associated distress after the intervention were sustained after maintenance. Innovations to expand reach (eg, telemedicine-enabled shared appointments) and sustainability are needed., Trial Registration: ClinicalTrials.gov Identifier: NCT01876485.

A 40-year-old woman with silicone implants inserted 21 years before presented with sudden onset of painful right breast swelling. Clinical examination revealed a firm swollen breast with appearance of old bruising. Ultrasound showed fluid around the implant. Cytology of the fluid showed cells with large pleomorphic nuclei with prominent nucleoli including elongated forms and very occasional vacuoles. The cell block also contained small fragments with atypical spindle cells around slit-like spaces that were positive for CD31 and CD34. MRI showed a 25 mm serpiginous area of enhancement on the inner aspect of the fibrous capsule with haematoma between the capsule and the implant. The capsule and adjacent area were excised. Histology showed angiosarcoma extending from the inner aspect of the capsule into the cavity around the implant. The location of the tumour on the inner aspect of the capsule is the same site that breast implant associated anaplastic large cell lymphomas arise and suggests a possible causal link between the implant and the angiosarcoma. This case emphasises the value of cytological assessment of fluid around breast implants and the role of cell blocks and immunohistochemistry., (© 2022 Wiley Periodicals LLC.)

Background: Prehospital automated large vessel occlusion (LVO) detection in Mobile Stroke Units (MSUs) could accelerate identification and treatment of patients with LVO acute ischemic stroke. Here, we evaluate the performance of a machine learning (ML) model on CT angiograms (CTAs) obtained from 2 MSUs to detect LVO., Methods: Patients evaluated on MSUs in Houston and Los Angeles with out-of-hospital CTAs were identified. Anterior circulation LVO was defined as an occlusion of the intracranial internal carotid artery, middle cerebral artery (M1 or M2), or anterior cerebral artery vessels and determined by an expert human reader. A ML model to detect LVO was trained and tested on independent data sets consisting of in-hospital CTAs and then tested on MSU CTA images. Model performance was determined using area under the receiver-operator curve statistics., Results: Among 68 patients with out-of-hospital MSU CTAs, 40% had an LVO. The most common occlusion location was the middle cerebral artery M1 segment (59%), followed by the internal carotid artery (30%), and middle cerebral artery M2 (11%). Median time from last known well to CTA imaging was 88.0 (interquartile range, 59.5-196.0) minutes. After training on 870 in-hospital CTAs, the ML model performed well in identifying LVO in a separate in-hospital data set of 441 images with area under receiver-operator curve of 0.84 (95% CI, 0.80-0.87). ML algorithm analysis time was under 1 minute. The performance of the ML model on the MSU CTA images was comparable with area under receiver-operator curve 0.80 (95% CI, 0.71-0.89). There was no significant difference in performance between the Houston and Los Angeles MSU CTA cohorts., Conclusions: In this study of patients evaluated on MSUs in 2 cities, a ML algorithm was able to accurately and rapidly detect LVO using prehospital CTA acquisitions.

Purpose: There is increasing use of open-bore vertical MR systems that consist of two planar RF coils. A recent study showed that the RF-induced heating of a neuromodulation device was much lower in the open-bore system at the brain and the chest imaging landmarks. This study focused on the hip and knee implants and compared the specific absorption rate (SAR) distribution in human models in a 1.2T open-bore coil with that of a 1.5T conventional birdcage coil., Methods: Computational modeling results were compared against the measurement values using a saline phantom. The differences in RF exposure were examined between a 1.2T open-bore coil and a 1.5T conventional birdcage coil using SAR in an anatomical human model., Results: Modeling setups were validated. The body placed closed to the coil elements led to high SAR values in the birdcage system compared with the open-bore system., Conclusion: Our computational modeling showed that the 1.2T planar system demonstrated a lower intensity of SAR distribution adjacent to hip and knee implants compared with the 1.5T conventional birdcage system., (© 2021 International Society for Magnetic Resonance in Medicine. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Background: The Coronavirus Aid, Relief, and Economic Security Act of 2020 provided 'economic impact payments' (EIPs) of $1200 to US adults with annual personal income of $75 000 or less. This study examined the prospective association between EIP receipt and mental health outcomes., Methods: A nationally representative sample of 3169 middle-income and low-income US adults completed a baseline assessment of their health and well-being in May-June 2020 and a 3-month follow-up assessment during the period of the COVID-19 pandemic when EIPs were distributed., Results: Controlling for sociodemographic characteristics, EIP recipients had higher odds of reporting a positive COVID-19 test, endorsing a history of post-traumatic stress disorder and reporting any illicit drug use in the past month than participants who did not receive EIP. Participants who did not receive EIP were more likely to report a history of anxiety disorder or alcohol use disorder and recent suicidal ideation than EIP recipients. There was no association between EIP receipt and financial distress, although over one-third to over half of EIP recipients were not employed at baseline. Between baseline and 3-month follow-up, receipt of EIP was significantly associated with reduced medical conditions and alcohol use problems, but increased depression, suicidal ideation and COVID-19 era-related stress., Conclusion: The EIP provided a brief income stimulus to many adults in need but was not associated with improvements in financial distress or mental health among middle-income and low-income recipients. Long-term income security and employment may be more important to improving and sustaining positive mental health outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Cervical cancer screening rates are suboptimal in the US. Population-based assessment of reasons for not receiving screening is needed, particularly among women from historically underserved demographic groups., Objective: To estimate changes in US Preventive Service Task Force guideline-concordant cervical cancer screening over time and assess the reasons women do not receive up-to-date screening by sociodemographic factors., Design, Setting, and Participants: This pooled population-based cross-sectional study used data from the US National Health Interview Survey from 2005 and 2019. A total of 20 557 women (weighted, 113.1 million women) aged 21 to 65 years without previous hysterectomy were included. Analyses were conducted from March 30 to August 19, 2021., Exposures: Sociodemographic factors, including age, race and ethnicity, sexual orientation, rurality of residence, and health insurance type., Main Outcomes and Measures: Primary outcomes were US Preventive Services Task Force guideline-concordant cervical cancer screening rates and self-reported primary reasons for not receiving up-to-date screening. For 2005, up-to-date screening was defined as screening every 3 years for women aged 21 to 65 years. For 2019, up-to-date screening was defined as screening every 3 years with a Papanicolaou test alone for women aged 21 to 29 years and screening every 3 years with a Papanicolaou test alone or every 5 years with high-risk human papillomavirus testing or cotesting for women aged 30 to 65 years. Population estimation included sampling weights., Results: Among 20 557 women (weighted, 113.1 million women) included in the study, most were aged 30 to 65 years (16 219 women; weighted, 86.3 million women [76.3%]) and had private insurance (13 571 women; weighted, 75.8 million women [67.0%]). With regard to race and ethnicity, 997 women (weighted, 6.9 million women [6.1%]) were Asian, 3821 women (weighted, 19.5 million women [17.2%]) were Hispanic, 2862 women (weighted, 14.8 million women [13.1%]) were non-Hispanic Black, 12 423 women (weighted, 69.0 million women [61.0%]) were non-Hispanic White, and 453 women (weighted, 3.0 million women [2.7%]) were of other races and/or ethnicities (including Alaska Native and American Indian [weighted, 955 000 women (0.8%)] and other single and multiple races or ethnicities [weighted, 2.0 million women (1.8%)]). In 2019, women aged 21 to 29 years had a significantly higher rate of overdue screening (29.1%) vs women aged 30 to 65 years (21.1%; P < .001). In both age groups, the proportion of women without up-to-date screening increased significantly from 2005 to 2019 (from 14.4% to 23.0%; P < .001). Significantly higher rates of overdue screening were found among those of Asian vs non-Hispanic White race and ethnicity (31.4% vs 20.1%; P = .01), those identifying as LGBQ+ (gender identity was not assessed because of a small sample) vs heterosexual (32.0% vs 22.2%; P < .001), those living in rural vs urban areas (26.2% vs 22.6%; P = .04), and those without insurance vs those with private insurance (41.7% vs 18.1%; P < .001). The most common reason for not receiving timely screening across all groups was lack of knowledge, ranging from 47.2% of women identifying as LGBQ+ to 64.4% of women with Hispanic ethnicity. Previous receipt of a human papillomavirus vaccine was not a primary reason for not having up-to-date screening (<1% of responses). From 2005 to 2019, among women aged 30 to 65 years, lack of access decreased significantly as a primary reason for not receiving screening (from 21.8% to 9.7%), whereas lack of knowledge (from 45.2% to 54.8%) and not receiving recommendations from health care professionals (from 5.9% to 12.0%) increased significantly., Conclusions and Relevance: This cross-sectional study found that cervical cancer screening that was concordant with US Preventive Services Task Force guidelines decreased in the US between 2005 and 2019, with lack of knowledge reported as the biggest barrier to receiving timely screening. Campaigns addressing patient knowledge and provider communication may help to improve screening rates, and cultural adaptation of interventions is needed to reduce existing disparities.

Objective: Failure to follow-up on laboratory test results can lead to missed diagnoses, diagnostic delays, patient harm, and potential malpractice claims against providers. State-of-the-art tracking technologies such as the radio frequency identification (RFID) can potentially improve laboratory order processing and test result communication. We conducted a comparative evaluation of differences in completion rates for 5 testing process milestones and time to reach these process milestones, with and without RFID order tracking for skin biopsy orders., Methods: This observational study analyzed 48,515 orders from 20 dermatology providers, sent to 8 pathology laboratories in 2016 to 2017. Descriptive t tests and multiple Cox proportional hazard regressions were used to examine the differences in completion rates and times to the 5 testing process milestones, namely, (1) provider receipt of results, (2) provider review of results, (3) patient notification, (4) follow-up scheduling, and (5) order case closure, for orders processed with and without RFID order tracking., Results: Descriptive statistics illustrated that all 5 testing process milestone completion rates were statistically higher for RFID tracked orders compared with non-RFID tracked orders, and RFID tracked orders took 3 to 5 days lesser than non-RFID tracked orders to reach the 5 testing process milestones. Multiple cox proportional hazard regressions showed that the process milestones were achieved faster if orders were RFID tracked versus not (hazard ratios ranged from 1.3 to 4.9)., Conclusions: The RFID tracking technology considerably improved test result communication timeliness and reliability. Such technologies can be beneficial for laboratory order processing, and their effectiveness should be explored in other practice settings., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Studies face challenges with missing 5-level EQ-5D (EQ-5D-5L) data, often because of the need for longitudinal EQ-5D-5L data collection. There is a dearth of validated methodologies for dealing with missing EQ-5D-5L data in the literature. This study, for the first time, examined the possibility of using retrospectively collected EQ-5D-5L data as proxies for the missing data., Methods: Participants who had prospectively completed a 3rd month postdischarge EQ-5D-5L instrument (in-the-moment collection) were randomly interviewed to respond to a 2nd "retrospective collection" of their 3rd month EQ-5D-5L at 6th, 9th, or 12th month after hospital discharge. A longitudinal single imputation was also used to assess the relative performance of retrospective collection compared with the longitudinal single imputation. Concordances between the in-the-moment, retrospective, and imputed measures were assessed using intraclass correlation coefficients and weighted kappa statistics., Results: Considerable agreement was observed on the basis of weighted kappa (range 0.72-0.95) between the mobility, self-care, and usual activities dimensions of EQ-5D-5L collected in-the-moment and retrospectively. Concordance based on intraclass correlation coefficients was good to excellent (range 0.79-0.81) for utility indices computed, and excellent (range 0.93-0.96) for quality-adjusted life-years computed using in-the-moment compared with retrospective EQ-5D-5L. The longitudinal single imputation did not perform as well as the retrospective collection method., Conclusions: This study demonstrates that retrospective collection of EQ-5D-5L has high concordance with "in-the-moment" EQ-5D-5L and could be a valid and attractive alternative for data imputation when longitudinally collected EQ-5D-5L data are missing. Future studies examining this method for other disease areas and populations are required to provide more generalizable evidence., (Copyright © 2021 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Informing end-stage kidney disease patients about kidney transplantation options increases the likelihood of kidney transplant waiting list (WL) enrollment and live donor kidney transplant (LDKT) receipt. Patients in for-profit dialysis centers have lower rates of WL enrollment and LDKT receipt. This study examined if the ownership status of dialysis centers modified the association between informing patients about transplantation options and patients' transplantation status. Multilevel analysis using mixed-effect multinomial logistic regression was performed using the United States Renal Data System (USRDS) data (January 2005 to December 2017). The study showed that informing patients improved the odds of WL enrollment and LDKT receipt. However, the effect of informing patients on transplantation status was less pronounced at for-profit as compared with nonprofit centers (Nonprofit: WL enrollment OR: 2.23 [95% CI: 2.07-2.40], and LDKT receipt OR: 3.35 [95% CI: 2.65-4.25]. For-profit: WL enrollment OR: 1.73 [95% CI: 1.66-1.79], and LDKT receipt OR: 2.35 [95% CI: 2.08-2.66]), although the odds of informing patients was higher for for-profit centers, and type of patients informed were similar across both types of centers. Information provided by for-profit centers was potentially less effective than those provided by nonprofit centers. Standardized guidelines for transplantation information provision are needed in order to ensure similar informational quality across centers., (© 2021 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Background: There is a lack of data-driven evidence about the burden of homelessness, and lack of a holistic measure of effectiveness for evaluating interventions targeting homelessness. Quality-adjusted life years (QALYs) can help holistically capture the burden of homelessness, and facilitate the valuation and comparison of interventions designed to address homelessness., Objective: This study estimated utility values required to compute the QALYs associated with homelessness, and also examined individual-level characteristics that affect these values., Research Design: The study is cross-sectional and derived from a large national survey conducted during the coronavirus disease 2019 pandemic., Subjects: A sample of 6607 middle- and low-income adults in the United States., Measures: A self-completion standard gamble survey was used to estimate utility values associated with homelessness. Linear regression was used to analyze the association between individual-level characteristics and these utility values., Results: The study estimated the average utility value associated with homelessness as 43.4% among the study participants. This implies that 1 year of life as a homeless individual is perceived to be equivalent to less than half a year of life as a stably housed individual in good health. The study also found that individuals who have experienced homelessness and financial distress value life as a homeless person considerably less than those who have not had these experiences., Conclusions: The method developed in this study can be used to estimate QALYs in studies evaluating homelessness interventions, thereby establishing the societal value of these interventions and informing policy and budgetary decision-making. Future studies estimating the utility values associated with homelessness in the general population, as well as specific homeless groups, are required to provide more generalizable evidence., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The Internet is a major resource for surgery fellowship applicants, especially during the COVID-19 pandemic. Online information for surgical oncology and breast oncology training programs can be found on the Society of Surgical Oncology's webpage and fellowship institution websites. The goal of this study was to analyze the comprehensiveness of complex general surgical oncology and breast oncology fellowship websites., Materials and Methods: A list of all accredited surgical oncology and breast oncology fellowships was recorded from the Society of Surgical Oncology website and stratified by region. Then, a Google search was performed on each fellowship program to determine each institution's webpage. Two of the authors then analyzed 2 web resources, institutional website and Society of Surgical Oncology webpage, for each fellowship program to determine if information valued by applicants was provided., Results: Online information of 29 surgical oncology fellowships and 59 breast oncology fellowships was analyzed. Statistical differences were found among criteria in major information categories between Society of Surgical Oncology and institutional webpages for both fellowship types. Detailed criteria were more present on institutional rather than Society of Surgical Oncology webpages., Conclusion: For applicants to surgical oncology fellowships, institutional webpages provided the most pertinent information and may be used as a primary resource to guide fellowship application. For applicants to breast oncology fellowships, Society of Surgical Oncology webpages may be used as a primary resource to guide fellowship application. Both Society of Surgical Oncology and institutional pages lacked pertinent information regarding interview dates, and these resources should be updated to reflect program highlights as well as pertinent information for applicants., (© 2021 The Authors.)

Background: Mobile stroke units (MSUs) are ambulances with staff and a computed tomographic scanner that may enable faster treatment with tissue plasminogen activator (t-PA) than standard management by emergency medical services (EMS). Whether and how much MSUs alter outcomes has not been extensively studied., Methods: In an observational, prospective, multicenter, alternating-week trial, we assessed outcomes from MSU or EMS management within 4.5 hours after onset of acute stroke symptoms. The primary outcome was the score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes according to a patient value system, derived from scores on the modified Rankin scale of 0 to 6, with higher scores indicating more disability). The main analysis involved dichotomized scores on the utility-weighted modified Rankin scale (≥0.91 or <0.91, approximating scores on the modified Rankin scale of ≤1 or >1) at 90 days in patients eligible for t-PA. Analyses were also performed in all enrolled patients., Results: We enrolled 1515 patients, of whom 1047 were eligible to receive t-PA; 617 received care by MSU and 430 by EMS. The median time from onset of stroke to administration of t-PA was 72 minutes in the MSU group and 108 minutes in the EMS group. Of patients eligible for t-PA, 97.1% in the MSU group received t-PA, as compared with 79.5% in the EMS group. The mean score on the utility-weighted modified Rankin scale at 90 days in patients eligible for t-PA was 0.72 in the MSU group and 0.66 in the EMS group (adjusted odds ratio for a score of ≥0.91, 2.43; 95% confidence interval [CI], 1.75 to 3.36; P<0.001). Among the patients eligible for t-PA, 55.0% in the MSU group and 44.4% in the EMS group had a score of 0 or 1 on the modified Rankin scale at 90 days. Among all enrolled patients, the mean score on the utility-weighted modified Rankin scale at discharge was 0.57 in the MSU group and 0.51 in the EMS group (adjusted odds ratio for a score of ≥0.91, 1.82; 95% CI, 1.39 to 2.37; P<0.001). Secondary clinical outcomes generally favored MSUs. Mortality at 90 days was 8.9% in the MSU group and 11.9% in the EMS group., Conclusions: In patients with acute stroke who were eligible for t-PA, utility-weighted disability outcomes at 90 days were better with MSUs than with EMS. (Funded by the Patient-Centered Outcomes Research Institute; BEST-MSU ClinicalTrials.gov number, NCT02190500.)., (Copyright © 2021 Massachusetts Medical Society.)

Background: Hospital performance comparisons for transparency initiatives may be inadequate if peer comparison groups are poorly defined., Objective: The objective of this study was to evaluate a new approach identifying hospital peers for comparison., Design/setting: We used Mahalanobis distance as a new method of developing peer-specific groupings for hospitals to incorporate both external and internal complexity. We compared the overlap in groups with an existing method used by the Veterans' Health Administration's Office for Productivity, Efficiency, and Staffing (OPES)., Participants: One hundred twenty-two acute-care Veterans' Health Administration's Medical Facilities as defined in the OPES fiscal year 2014 report., Measures: Using 15 variables in 9 categories developed from expert input, including both hospital internal measures and community-based external measures, we used principal components analysis and calculated Mahalanobis distance between each hospital pair. This method accounts for correlation between variables and allows for variables having different variances. We identified the 50 closest hospitals, then eliminated any potential peer whose score on the first component was >1 SD from the reference hospital. We compared overlap with OPES measures., Results: Of 15 variables, 12 have SDs exceeding 25% of their means. The first 2 components of our analysis explain 24.8% and 18.5% of variation among hospitals. Eight of 9 variables scaling positively on the first component measure internal complexity, aligning with OPES groups. Four of 5 variables scaling positively on the second component but not the first are factors from the policy environment; this component reflects a dimension not considered in OPES groups., Conclusion: Individualized peers that incorporate external complexity generate more nuanced comparators to evaluate quality., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The American Heart Association recently raised the bar on the timely treatment of acute ischemic stroke (AIS) with intravenous alteplase. Our study looks at the effectiveness of this new standard, by examining the effect of varying door-to-needle times of alteplase initiation on the clinical, quality of care, and efficiency of care outcomes., Methods: This retrospective case-control study examined 752 AIS patients treated with intravenous alteplase in a large academic health system during 2015-2018, and compared their outcomes after treatment within 30, 45, and 60 min of arrival. The outcomes compared were: (1) clinical - discharge and 90-day modified Rankin Scale (mRS), and post-intravenous alteplase (24-h) NIH Stroke Scale (NIHSS); (2) quality of care - inpatient mortality, 30-day readmission, discharge to home, and disability at discharge; (3) efficiency of care - length of stay (LOS) and index stroke hospitalization costs. Adjusted logistic and linear regression analyses were used to estimate the effects, after controlling for baseline characteristics., Results: Based on the adjusted regression analyses, treatment within 30 min of arrival was associated with better post-treatment mRS and NIHSS scores, and the clinical benefits were reduced when the windows were expanded to within 45 or 60 min. An important finding of the study was that treatment within 30 min of arrival significantly reduced the average LOS., Interpretation: Early intravenous alteplase treatment significantly improved clinical and efficiency of care outcomes. This study provides evidence that meeting the new AHA Target Stroke recommendations will help hospitals improve patient clinical outcomes and reduce LOS, thereby improving the efficiency of care standards., (© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

ABSTRACT Opportunistic infections (OIs) are the primary cause of HIV-related morbidity and mortality. To reduce the risk, the ART eligibility criteria were revised to start treatment before advanced disease onset. We evaluated the effect of 2014 HIV clinical guideline changes in Uganda on opportunistic infections and survival among Youth Living with HIV (YLWH). This retrospective cohort analysis used administrative data from the District Health Information System (DHIS2) and the national referral hospital, to compare YLWH, 15-24 years old, who started ART pre-guideline (January 2012-June 2014) and post-guideline (July 2014-December 2016). We assessed the effect using multivariable logistic and Cox Proportional Hazards regression models, respectively. Post-guideline youth had 18% and 30% lower adjusted odds of having an OI at 6 (aOR: 0.82, 95%CI: 0.67, 0.99), and 12 months (aOR: 0.70, 95%CI: 0.58, 0.85) after ART initiation, compared to pre-guideline youth. No significant differences were observed in survival probabilities (Z = 2.56, P -value = 0.11) and adjusted hazard ratios (aHR: 1.55, 95%CI: 0.46, 5.28). Early ART initiation reduced the risk of OIs among YLWH. However, given the existence of geographical and clinical variations in the endemicity, morbidity and mortality associated with different OIs, additional research is still needed.

Background: Significant primary care provider (PCP) shortage exists in the United States. Expanding the scope of practice for nurse practitioners (NPs) and physician assistants (PAs) can help alleviate this shortage. The Department of Veterans' Affairs (VA) has been a pioneer in expanding the role of NPs and PAs in primary caregiving., Purpose: This study evaluated the health care costs associated with VA patients cared for by NPs and PAs versus primary care physicians (physicians)., Methods: A retrospective data analysis using two separate cohorts of VA patients, one with diabetes and the other with cardiovascular disease (CVD), was performed. The associations between PCP type and health care costs were analyzed using ordinary least square regressions with logarithmically transformed costs., Results: The analyses estimated 12% to 13% (US dollars [USD] 2,626) and 4% to 5% (USD 924) higher costs for patients assigned to physicians as compared with those assigned to NPs and PAs, after adjusting for baseline patient sociodemographics and disease burden, in the diabetes and CVD cohort, respectively. Given the average patient population size of a VA medical center, these cost differences amount to a total difference of USD 14 million/year per center and USD 5 million/year per center for diabetic and CVD patients, respectively., Implications for Practice: This study highlights the potential cost savings associated with primary caregiving by NPs and PAs. In light of the PCP shortage, the study supports increased involvement of NPs and PAs in primary caregiving. Future studies examining the reasons for these cost differences by provider type are required to provide more scientific evidence for regulatory decision making in this area., Competing Interests: Competing interests: C. M. Ballantyne—grant/research support: all significant (paid to institution, not individual): Abbott Diagnostic, Amarin, Amgen, Eli Lilly, Esperion, Novartis, Pfizer, Otsuka, Regeneron, Roche Diagnostic, Sanofi-Synthelabo, Takeda, NIH, AHA, ADA; consultant: Abbott Diagnostics, Amarin, Amgen*, Astra Zeneca*, Eli Lilly, Esperion, Genzyme, ISIS, Matinas BioPharma Inc, Merck*, Novartis, Pfizer*, Regeneron, Sanofi-Synthelabo. *Significant where noted (>USD 10,000); remainder modest (

Advances in cancer genomics have revealed genomic classes of acute myeloid leukemia (AML) characterized by class-defining mutations, such as chimeric fusion genes or in genes such as NPM1, MLL, and CEBPA. These class-defining mutations frequently synergize with internal tandem duplications in FLT3 (FLT3-ITDs) to drive leukemogenesis. However, ∼20% of FLT3-ITD-positive AMLs bare no class-defining mutations, and mechanisms of leukemic transformation in these cases are unknown. To identify pathways that drive FLT3-ITD mutant AML in the absence of class-defining mutations, we performed an insertional mutagenesis (IM) screening in Flt3-ITD mice, using Sleeping Beauty transposons. All mice developed acute leukemia (predominantly AML) after a median of 73 days. Analysis of transposon insertions in 38 samples from Flt3-ITD/IM leukemic mice identified recurrent integrations at 22 loci, including Setbp1 (20/38), Ets1 (11/38), Ash1l (8/38), Notch1 (8/38), Erg (7/38), and Runx1 (5/38). Insertions at Setbp1 led exclusively to AML and activated a transcriptional program similar, but not identical, to those of NPM1-mutant and MLL-rearranged AMLs. Guide RNA targeting of Setbp1 was highly detrimental to Flt3ITD/+/Setbp1IM+, but not to Flt3ITD/+/Npm1cA/+, AMLs. Also, analysis of RNA-sequencing data from hundreds of human AMLs revealed that SETBP1 expression is significantly higher in FLT3-ITD AMLs lacking class-defining mutations. These findings propose that SETBP1 overexpression collaborates with FLT3-ITD to drive a subtype of human AML. To identify genetic vulnerabilities of these AMLs, we performed genome-wide CRISPR-Cas9 screening in Flt3ITD/+/Setbp1IM+ AMLs and identified potential therapeutic targets, including Kdm1a, Brd3, Ezh2, and Hmgcr. Our study gives new insights into epigenetic pathways that can drive AMLs lacking class-defining mutations and proposes therapeutic approaches against such cases., (© 2021 by The American Society of Hematology.)

Objective: To review the global impact of the COVID-19 pandemic on stroke care-metrics and report data from a health system in Houston., Methods: We performed a meta-analysis of the published literature reporting stroke admissions, intracerebral hemorrhage (ICH) cases, number of thrombolysis (tPA) and thrombectomy (MT) cases, and time metrics (door to needle, DTN; and door to groin time, DTG) during the pandemic compared to prepandemic period. Within our hospital system, between January-June 2019 and January-June 2020, we compared the proportion of stroke admissions and door to tPA and MT times., Results: A total of 32,640 stroke admissions from 29 studies were assessed. Compared to prepandemic period, the mean ratio of stroke admissions during the pandemic was 70.78% [95% CI, 65.02%, 76.54%], ICH cases was 83.10% [95% CI, 71.01%, 95.17%], tPA cases was 81.74% [95% CI, 72.33%, 91.16%], and MT cases was 88.63% [95% CI, 74.12%, 103.13%], whereas DTN time was 104.48% [95% CI, 95.52%, 113.44%] and DTG was 104.30% [95% CI, 81.99%, 126.61%]. In Houston, a total of 4808 cases were assessed. There was an initial drop of ~30% in cases at the pandemic onset. Compared to 2019, there was a significant reduction in mild strokes (NIHSS 1-5) [N (%), 891 (43) vs 635 (40), P = 0.02]. There were similar mean (SD) (mins) DTN [44 (17) vs 42 (17), P = 0.14] but significantly prolonged DTG times [94 (15) vs 85 (20), P = 0.005] in 2020., Interpretation: The COVID-19 pandemic led to a global reduction in stroke admissions and treatment interventions and prolonged treatment time metrics., (© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Most clinical research stopped during COVID due to possible impact on data quality and personnel safety. We aimed to assess the impact of COVID on acute stroke clinical trial conduct at sites that continued to enroll patients during the pandemic. BEST-MSU is an ongoing study of Mobile Stroke Units (MSU) vs standard management of tPA-eligible acute stroke patients in the pre-hospital setting. MSU personnel include a vascular neurologist via telemedicine, and a nurse, CT technologist, paramedics and emergency medicine technicians on-board. During COVID, consent, 90-day modified Rankin Scale (mRS) and EQ5D were obtained by phone instead of in-person, but other aspects of management were similar to the pre-COVID period. We compared patient demographics, study metrics, and infection of study personnel during intra- vs pre-COVID eras. Five of 6 BEST-MSU sites continued to enroll during COVID. There were no differences in intra- (n = 57) vs pre- (n = 869) COVID enrolled tPA eligible patients' age, sex, race (38.6% vs 38.0% Black), ethnicity (15.8% vs 18.6% Hispanic), or NIHSS (median 11 vs 9). The percent of screened patients enrolled and adjudicated tPA eligible declined from 13.6% to 6.6% (p < .001); study enrollment correlated with local stay-at-home and reopening orders. There were no differences in alert to MSU arrival or arrival to tPA times, but MSU on-scene time was 5 min longer (p = .01). There were no differences in ED door to CT, tPA treatment or thrombectomy puncture times, hospital length of stay, discharge disposition, or remote vs in-person 90-day mRS or EQ5D. One MSU nurse tested positive but did not require hospitalization. Clinical research in the pre-hospital setting can be carried out accurately and safely during a pandemic. tPA eligibility rates declined, but otherwise there were no differences in patient demographics, deterioration of study processes, or serious infection of study staff. Trial registration: NCT02190500., Competing Interests: The authors have declared that no competing interests exist.

Background: The 90-day modified Rankin Scale is a widely used outcome after stroke but is sometimes hard to ascertain due to loss to follow-up. Missing outcomes can result in biased and/or inefficient estimates in clinical trials. The aim of this study is to assess the validity of acquiring the 90-day modified Rankin Scale at a later point of time when the patient has been lost at 90 days to impute the missing value., Methods: Participants who had prospectively completed a 90-day modified Rankin Scale questionnaire on their own in the Benefits of Stroke Treatment Using a Mobile Stroke Unit study were randomly interviewed to recall the 90-day modified Rankin Scale at 6, 9, or 12 months after hospital discharge over the phone. Concordance between the two scores was assessed using kappa and weighted kappa statistics. Logistic regression was used to identify factors associated with inconsistent reporting of the 90-day modified Rankin Scale., Results: Substantial agreement was observed between in-the-moment and retrospective 90-day modified Rankin Scale recalled at 6, 9, or 12 months (weighted kappa = 0.93, 95% confidence interval: 0.89-0.98; weighted kappa = 0.93, 95% confidence interval: 0.85-1.00 and weighted kappa = 0.89, 95% confidence interval: 0.82-0.95, respectively)., Conclusion: Retrospective recall of 90-day modified Rankin Scale at a later time point is a valid means to impute missing data in stroke clinical trials.