tbuckley/cabot-search huggingface dataset:
Economic Evaluation of Population-Based <i>BRCA1</i> and <i>BRCA2</i> Testing in Canada
Authors: Li Sun, Xia Wei, Caitlin T. Fierheller, Lesa Dawson, Samuel Oxley, Ashwin Kalra, Jacqueline Sia, Fabio Feldman, Stuart Peacock, Kasmintan A. Schrader, Rosa Legood, Janice S. Kwon, Ranjit Manchanda
Journal: JAMA Network Open (2024)

Importance Population-based BRCA testing can identify many more BRCA carriers who will be missed by the current practice of BRCA testing based on family history (FH) and clinical criteria. These carriers can benefit from screening and prevention, potentially preventing many more breast and ovarian cancers and deaths than the current practice. Objective To estimate the incremental lifetime health outcomes, costs, and cost-effectiveness associated with population-based BRCA testing compared with FH-based testing in Canada. Design, Setting, and Participants For this economic evaluation, a Markov model was developed to compare the lifetime costs and outcomes of BRCA1/BRCA2 testing for all general population women aged 30 years compared with FH-based testing. BRCA carriers are offered risk-reducing salpingo-oophorectomy to reduce their ovarian cancer risk and magnetic resonance imaging (MRI) and mammography screening, medical prevention, and risk-reducing mastectomy to reduce their breast cancer risk. The analyses were conducted from both payer and societal perspectives. This study was conducted from October 1, 2022, to February 20, 2024. Main Outcomes and Measures Outcomes of interest were ovarian cancer, breast cancer, additional heart disease deaths, and incremental cost-effectiveness ratio ICER per quality-adjusted life-year (QALY). One-way and probabilistic-sensitivity-analyses (PSA) were undertaken to explore the uncertainty. Results In the simulated cohort of 1 000 000 women aged 30 years in Canada, the base case ICERs of population-based BRCA testing were CAD $32 276 (US $23 402.84) per QALY from the payer perspective or CAD $16 416 (US $11 903.00) per QALY from the societal perspective compared with FH-based testing, well below the established Canadian cost-effectiveness thresholds. Population testing remained cost-effective for ages 40 to 60 years but not at age 70 years. The results were robust for multiple scenarios, 1-way sensitivity, and PSA. More than 99% of simulations from payer and societal perspectives were cost-effective on PSA (5000 simulations) at the CAD $50 000 (US $36 254.25) per QALY willingness-to-pay threshold. Population-based BRCA testing could potentially prevent an additional 2555 breast cancers and 485 ovarian cancers in the Canadian population, corresponding to averting 196 breast cancer deaths and 163 ovarian cancer deaths per 1 000 000 population. Conclusions and Relevance In this economic evaluation, population-based BRCA testing was cost-effective compared with FH-based testing in Canada from payer and societal perspectives. These findings suggest that changing the genetic testing paradigm to population-based testing could prevent thousands of breast and ovarian cancers.
Active Visual Art Therapy and Health Outcomes
Authors: Ronja Joschko, Caroline Klatte, Weronika A. Grabowska, Stephanie Roll, Anne Berghöfer, Stefan N. Willich
Journal: JAMA Network Open (2024)

Importance Art therapy has a long-standing tradition in patient treatment. As scientific interest in its use has recently grown, a comprehensive assessment of active visual art therapy is crucial to understanding its potential benefits. Objective To assess the association of active visual art therapy with health outcomes across patient groups and comparators. Data Sources The systematic literature search included the Cochrane Library, Embase, MEDLINE, CINAHL, ERIC, American Psychological Association PsycArticles, American Psychological Association PsycInfo, PSYNDEX, the German Clinical Trials Register, and ClinicalTrials.gov. No filters regarding language were applied. The search covered all dates before March 2021. Data analysis was conducted from April 24 to September 8, 2023. Study Selection Randomized clinical trials with any type of patient population comparing the intervention with any control not using active visual art therapy were included. Two researchers independently screened the abstracts and full texts. Data Extraction and Synthesis Data extraction followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and study quality was evaluated using the Cochrane Risk of Bias tool. Data were synthesized using narrative summaries, forest plots, and random effects meta-analyses. Main Outcome and Measures In line with the protocol, all outcome measures of the included studies were extracted. Results The search identified 3104 records, of which 356 outcomes of 69 studies were included, with a total of approximately 4200 participants, aged 4 to 96 years, in the review. The meta-analyses included 50 studies and 217 outcomes of 2766 participants. Treatment indications included mental, neurological, and other somatic disorders, and prevention. Most outcome measures focused on depression, anxiety, self-esteem, social adjustment, and quality of life. Art therapy was associated with an improvement in 18% of the 217 outcomes compared with the controls (1%), while 81% showed no improvement. The standardized mean difference in the change from baseline of the meta-analyses of 0.38 (95% CI, 0.26-0.51) and posttest analysis of 0.19 (95% CI, 0.12-0.26) also indicated an improvement of outcomes associated with art therapy. Overall study quality was low. Conclusions and Relevance In this systematic review and meta-analysis of randomized clinical trials, visual art therapy was associated with therapeutic benefits for some outcomes, although most studies were of low quality. Further good-quality studies are needed to provide additional insights for its best possible integration into routine care.
Heterogeneity of Residual Disease After Neoadjuvant Systemic Therapy in Breast Cancer
Authors: Paolo Tarantino, Gabriel Hortobagyi, Sara M. Tolaney, Elizabeth A. Mittendorf
Journal: JAMA Oncology (2024)

Importance Over the past 2 decades, systemic therapy for early-stage breast cancer has gradually moved from the adjuvant to the neoadjuvant setting. Administration of systemic therapy before surgery leads to potential improvements in surgical outcomes and allows for the assessment of the pathologic response to treatment. For patients with residual disease (RD), 3 adjuvant strategies have been shown to improve outcomes: (1) adjuvant trastuzumab emtansine for ERBB2 -positive disease, (2) adjuvant capecitabine for triple-negative disease, and (3) adjuvant olaparib for patients with germline BRCA variants. Furthermore, studies are testing novel drugs in the postneoadjuvant setting. Given the potential to tailor adjuvant therapy based on the response to preoperative systemic therapy, recognizing the complexities of response to neoadjuvant therapy and moving beyond the binary paradigm of RD vs experiencing a pathologic complete response is becoming increasingly necessary. Observations Novel antibody-drug conjugates, anti- ERBB2 tyrosine kinase inhibitors, and immune checkpoint inhibitors are being evaluated as additional rescue options in phase 3 trials for patients with RD after neoadjuvant treatment. Concomitantly, the prognostic role of RD has been refined by the introduction of the residual cancer burden. In addition, the genomic landscape of RD has been found to be associated with long-term prognosis, as has the immune background of the disease evaluated via the presence of tumor-infiltrating lymphocytes. Lastly, the dynamics of circulating tumor DNA may allow for further improvement in prognostication by understanding which patients harbor detectable minimal RD. Conclusions and Relevance Escalating adjuvant treatment has led to meaningful survival improvements among patients with breast cancer and RD after neoadjuvant therapy. Uncovering the anatomic and biological intricacies of RD will allow for increased precision in postneoadjuvant treatments, moving beyond the binary paradigm of RD vs pathologic complete response, toward more tailored rescue strategies in the adjuvant setting.
Radiation-Associated Secondary Cancer in Patients With Breast Cancer Harboring <i>TP53</i> Germline Variants
Authors: Gustav Y. Cederquist, Lillian A. Boe, Michael Walsh, Gary M. Freedman, Kara N. Maxwell, Neil Taunk, Lior Z. Braunstein
Journal: JAMA Oncology (2024)

This cohort study examines the risk of radiation-associated sarcoma in patients with breast cancer harboring germline TP53 variants.
Tenecteplase vs Alteplase for Patients With Acute Ischemic Stroke
Authors: Xia Meng, Shuya Li, Hongguo Dai, Guozhi Lu, Weiwei Wang, Fengyuan Che, Yu Geng, Minghui Sun, Xiyan Li, Hao Li, Yongjun Wang
Journal: JAMA (2024)

Importance Tenecteplase is a bioengineered variant of alteplase with greater fibrin specificity and a longer half-life, allowing single-bolus administration. Evidence on the treatment effect of tenecteplase 0.25 mg/kg in Chinese patients with acute ischemic stroke (AIS) is limited. Objective To establish the noninferiority of tenecteplase to alteplase in patients with AIS within 4.5 hours of symptom onset. Design, Setting, and Participants The ORIGINAL study was a multicenter, active-controlled, parallel-group, randomized, open-label, blinded end point, noninferiority trial conducted between July 14, 2021, and July 14, 2023. Participants were recruited from 55 neurology clinics and stroke centers in China and were eligible if they had AIS with a National Institutes of Health Stroke Scale score of 1 to 25 with measurable neurologic deficit and were symptomatic for at least 30 minutes without significant improvement. Interventions Patients were randomized (1:1) within 4.5 hours of symptom onset to receive intravenous tenecteplase (0.25 mg/kg) or intravenous alteplase (0.9 mg/kg). Main Outcomes and Measures The primary outcome was the proportion of patients with a modified Rankin Scale (mRS) score of 0 or 1 (no symptoms or no significant disability) at day 90, tested for noninferiority (risk ratio [RR] margin, 0.937). Safety end points included symptomatic intracerebral hemorrhage (per European Cooperative Acute Stroke Study III definition) and 90-day all-cause mortality. Results Among the 1489 patients randomized, 1465 patients were included in the full analysis set (732 in the tenecteplase group; 733 in the alteplase group) and 446 (30.4%) were female. The primary outcome occurred in 72.7% (532/732) of patients receiving tenecteplase and 70.3% (515/733) receiving alteplase (RR, 1.03 [95% CI, 0.97-1.09]; noninferiority threshold met). Symptomatic intracerebral hemorrhage occurred in 9 patients (1.2%) in each group (RR, 1.01 [95% CI, 0.37-2.70]). The 90-day mortality rate was 4.6% (34/732) in the tenecteplase group and 5.8% (43/736) in the alteplase group (RR, 0.80 [95% CI, 0.51-1.23]). Conclusions and Relevance In patients with AIS eligible for intravenous thrombolysis within 4.5 hours after stroke onset, tenecteplase was noninferior to alteplase with respect to excellent functional outcome (mRS score of 0 or 1) at 90 days and had a similar safety profile. Findings from this study support tenecteplase as a suitable alternative to alteplase in this setting. Trial Registration ClinicalTrials.gov Identifier: NCT04915729
From bytes to bedside: a systematic review on the use and readiness of artificial intelligence in the neonatal and pediatric intensive care unit
Authors: Janno S Schouten, Melissa A C M Kalden, Eris van Twist, Irwin K M Reiss, Diederik A M P J Gommers, Michel E van Genderen, H Rob Taal
Journal: Intensive Care Medicine (2024)
Progress Toward Poliomyelitis Eradication — Pakistan, January 2023–June 2024
Authors: Miwako Kobayashi, Andrew J. Leidner, Ryan Gierke, Jennifer L. Farrar, Rebecca L. Morgan, Doug Campos-Outcalt, Robert Schechter, Katherine A. Poehling, Sarah S. Long, Jamie Loehr, Adam L. Cohen
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Since its launch in 1988, the Global Polio Eradication Initiative has made substantial progress toward the eradication of wild poliovirus (WPV), including eradicating two of the three serotypes, and reducing the countries with ongoing endemic transmission of WPV type 1 (WPV1) to just Afghanistan and Pakistan. Both countries are considered a single epidemiologic block. Despite the occurrence of only a single confirmed WPV1 case during the first half of 2023, Pakistan experienced widespread circulation of WPV1 over the subsequent 12 months, specifically in the historical reservoirs of the cities of Karachi, Peshawar, and Quetta. As of June 30, 2024, eight WPV1 cases had been reported in Pakistan in 2024, compared with six reported during all of 2023. These cases, along with more than 300 WPV1-positive environmental surveillance (sewage) samples reported during 2023-2024, indicate that Pakistan is not on track to interrupt WPV1 transmission. The country's complex sociopolitical and security environment continues to pose formidable challenges to poliovirus elimination. To interrupt WPV1 transmission, sustained political commitment to polio eradication, including increased accountability at all levels, would be vital for the polio program. Efforts to systematically track and vaccinate children who are continually missed during polio vaccination activities should be enhanced by better addressing operational issues and the underlying reasons for community resistance to vaccination and vaccine hesitancy.
Use of 21-Valent Pneumococcal Conjugate Vaccine Among U.S. Adults: Recommendations of the Advisory Committee on Immunization Practices — United States, 2024
Authors: Miwako Kobayashi, Andrew J. Leidner, Ryan Gierke, Jennifer L. Farrar, Rebecca L. Morgan, Doug Campos-Outcalt, Robert Schechter, Katherine A. Poehling, Sarah S. Long, Jamie Loehr, Adam L. Cohen
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

On June 17, 2024, the Food and Drug Administration approved 21-valent pneumococcal conjugate vaccine (PCV) (PCV21; CAPVAXIVE; Merck Sharp & Dohme, LLC) for adults aged ≥18 years. PCV21 does not contain certain serotypes that are included in other licensed pneumococcal vaccines but adds eight new serotypes. The Advisory Committee on Immunization Practices (ACIP) recommends use of a PCV for all adults aged ≥65 years, as well as adults aged 19-64 years with certain risk conditions for pneumococcal disease if they have not received a PCV or whose vaccination history is unknown. Previously, options included either 20-valent PCV (PCV20; Prevnar20; Wyeth Pharmaceuticals, Inc.) alone or a 15-valent PCV (PCV15; VAXNEUVANCE; Merck Sharp & Dohme, LLC) in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23; Pneumovax23; Merck Sharp & Dohme, LLC). Additional recommendations for use of PCV20 exist for adults who started their pneumococcal vaccination series with 13-valent PCV (PCV13; Prevnar13; Wyeth Pharmaceuticals, Inc.). The ACIP Pneumococcal Vaccines Work Group employed the Evidence to Recommendations framework to guide its deliberations on PCV21 vaccination among U.S. adults. On June 27, 2024, ACIP recommended a single dose of PCV21 as an option for adults aged ≥19 years for whom PCV is currently recommended. Indications for PCV have not changed from previous recommendations. This report summarizes evidence considered for these recommendations and provides clinical guidance for use of PCV21.
Progress Toward Achieving National HIV/AIDS Strategy Goals for Quality of Life Among Persons Aged ≥50 Years with Diagnosed HIV — Medical Monitoring Project, United States, 2017–2023
Authors: Linda Beer, Yunfeng Tie, Stacy M. Crim, John Weiser, Jennifer Taussig, Jason A. Craw, Kate A. Buchacz, Ashanté Dobbs, Charles B. Collins, Marie E. Johnston, Andrew De Los Reyes, Deborah Gelaude, Kamal Hughes, Rodel Desamu-Thorpe, Joseph Prejean
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Ensuring good quality of life (QoL) among persons with diagnosed HIV (PWH) is a priority of the National HIV/AIDS Strategy (NHAS), which established 2025 goals for improving QoL. Goals are monitored through five indicators: self-rated health, unmet needs for mental health services, unemployment, hunger or food insecurity, and unstable housing or homelessness. Among the growing population of PWH aged ≥50 years, progress toward these goals has not been assessed. Data collected during the 2017-2022 cycles of the Medical Monitoring Project, an annual complex sample survey of U.S. adults with diagnosed HIV, assessed progress toward NHAS 2025 QoL goals among PWH aged ≥50 years, overall and by age group. The recent estimated annual percentage change from baseline (2017 or 2018) to 2022 was calculated for each indicator. Among PWH aged ≥50 years, the 2025 goal of 95% PWH with good or better self-rated health is 46.2% higher than the 2022 estimate. The 2025 goals of a 50% reduction in the other indicators range from 26.3% to 56.3% lower than the 2022 estimates. Decreasing hunger or food insecurity by 50% among PWH aged ≥65 was the only goal met by 2022. If recent trends continue, other NHAS QoL 2025 goals are unlikely to be met. Multisectoral strategies to improve access to housing, employment, food, and mental health will be needed to meet NHAS 2025 goals for QoL among older PWH.
Use of <i>Haemophilus influenzae</i> Type b–Containing Vaccines Among American Indian and Alaska Native Infants: Updated Recommendations of the Advisory Committee on Immunization Practices ― United States, 2024
Authors: Jennifer P. Collins, Jamie Loehr, Wilbur H. Chen, Matthew Clark, Veronica Pinell-McNamara, Lucy A. McNamara
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Invasive Haemophilus influenzae type b (Hib) disease is a serious bacterial infection that disproportionally affects American Indian and Alaska Native (AI/AN) populations. Hib vaccination with a monovalent Hib conjugate vaccine consisting of Hib capsular polysaccharide (polyribosylribitol phosphate [PRP]) conjugated to outer membrane protein complex of Neisseria meningitidis serogroup B, PRP-OMP (PedvaxHIB, Merck and Co., Inc.) has historically been preferred for AI/AN infants, who are at increased risk for invasive Hib disease, because it provides substantial protection after the first dose. On June 26, 2024, CDC's Advisory Committee on Immunization Practices (ACIP) recommended that a hexavalent, combined diphtheria and tetanus toxoids and acellular pertussis (DTaP), inactivated poliovirus (IPV), Hib conjugate, and hepatitis B (HepB) vaccine, DTaP-IPV-Hib-HepB (Vaxelis, MSP Vaccine Company) should be included with monovalent PRP-OMP in the preferential recommendation for AI/AN infants because of the PRP-OMP Hib component. A primary Hib vaccination series consisting of either 1) monovalent PRP-OMP (2-dose series at ages 2 and 4 months) or 2) DTaP-IPV-Hib-HepB (3-dose series at ages 2, 4, and 6 months) is preferred for AI/AN infants. DTaP-IPV-Hib-HepB is only indicated for use in infants at ages 2, 4, and 6 months and should not be used for the booster doses of Hib, DTaP, or IPV vaccines. For the booster dose of Hib vaccine, no vaccine formulation is preferred for AI/AN children; any Hib vaccine (except DTaP-IPV-Hib-HepB) should be used. This report summarizes evidence considered for these recommendations and provides clinical guidance for the use of Hib-containing vaccines among AI/AN infants and children.
Real‐world efficacy and safety of luspatercept and predictive factors of response in patients with transfusion‐dependent β‐thalassemia
Authors: Daniele Lello Panzieri, Dario Consonni, Natalia Scaramellini, Guido Ausenda, Francesca Granata, Nancy Caponio, Lorena Duca, Simona Leoni, Silvia Elli, Marta Ferraresi, Vittorio Bolis, Cristina Curcio, Milena Agata Irrera, Diletta Maira, Giovanna Graziadei, Elena Cassinerio, Maria Domenica Cappellini, Rayan Bou‐Fakhredin, Valentina Brancaleoni, Irene Motta
Journal: American Journal of Hematology (2024)
Effectiveness of modified vaccinia Ankara-Bavarian Nordic vaccine against mpox infection: emulation of a target trial
Authors: Christine Navarro, Cindy Lau, Sarah A Buchan, Ann N Burchell, Sharifa Nasreen, Lindsay Friedman, Evaezi Okpokoro, Peter C Austin, Darrell H S Tan, Jonathan B Gubbay, Jeffrey C Kwong, Sharmistha Mishra
Journal: BMJ (2024)

To estimate the real world effectiveness of modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine against mpox infection.
Hepatocellular Carcinoma Immune Microenvironment Analysis: A Comprehensive Assessment with Computational and Classical Pathology
Authors: Caner Ercan, Salvatore Lorenzo. Renne, Luca Di Tommaso, Charlotte K.Y. Ng, Salvatore Piscuoglio, Luigi M. Terracciano
Journal: Clinical Cancer Research (2024)

Abstract Purpose: The spatial variability and clinical relevance of the tumour immune microenvironment (TIME) are still poorly understood for hepatocellular carcinoma (HCC). Here we aim to develop a deep learning (DL)-based image analysis model for the spatial analysis of immune cell biomarkers, and microscopically evaluate the distribution of immune infiltration. Experimental Design: Ninety-two HCC surgical liver resections and 51 matched needle biopsies were histologically classified according to their immunophenotypes: inflamed, immune-excluded, and immune-desert. To characterise the TIME on immunohistochemistry (IHC)-stained slides, we designed a multi-stage DL algorithm, IHC-TIME, to automatically detect immune cells and their localisation in TIME in tumour-stromal, centre-border segments. Results: Two models were trained to detect and localise the immune cells on IHC-stained slides. The framework models, i.e. immune cell detection models and tumour-stroma segmentation, reached 98% and 91% accuracy, respectively. Patients with inflamed tumours showed better recurrence-free survival than those with immune-excluded or immune desert tumours. Needle biopsies were found to be 75% accurate in representing the immunophenotypes of the main tumour. Finally, we developed an algorithm that defines immunophenotypes automatically based on the IHC-TIME analysis, achieving an accuracy of 80%. Conclusions: Our DL-based tool can accurately analyse and quantify immune cells on IHC-stained slides of HCC. The microscopical classification of the TIME can stratify HCCs according to the patient prognosis. Needle biopsies can provide valuable insights for TIME-related prognostic prediction, albeit with specific constraints. The computational pathology tool provides a new way to study the HCC TIME.
Cybersecurity and the blood supply: The vulnerabilities of the technological revolution
Authors: Jeremy W. Jacobs, Nicole De Simone, Miriam Andrea Duque, Yanyun Wu, Dawn C. Ward, Jennifer S. Woo, Laura D. Stephens, Elizabeth S. Allen, Mandy F. O'Leary, Sheharyar Raza, Garrett S. Booth, Brian D. Adkins
Journal: American Journal of Hematology (2024)