tbuckley/cabot-search huggingface dataset:
Prostate-Specific Membrane Antigen: Gateway to Management of Advanced Prostate Cancer
Authors: Lena M. Unterrainer, Jeremie Calais, Neil H. Bander
Journal: Annual Review of Medicine (2024)

Prostate-specific membrane antigen (PSMA) as a transmembrane protein is overexpressed by prostate cancer (PC) cells and is accessible for binding antibodies or low-molecular-weight radioligands due to its extracellular portion. Successful targeting of PSMA began with the development of humanized J591 antibody. Due to their faster clearance compared to antibodies, small-molecule radioligands for targeted imaging and therapy of PC have been favored in recent development efforts. PSMA positron emission tomography (PET) imaging has higher diagnostic performance than conventional imaging for initial staging of high-risk PC and biochemical recurrence detection/localization. However, it remains to be demonstrated how to integrate PSMA PET imaging for therapy response assessment and as an outcome endpoint measure in clinical trials. With the recent approval of 177 Lu-PSMA-617 by the US Food and Drug Administration for metastatic castration-resistant PC progressing after chemotherapy, the high value of PSMA-targeted therapy was confirmed. Compared to standard of care, PSMA-based radioligand therapy led to a better outcome and a higher quality of life. This review, focusing on the advanced PC setting, provides an overview of different approved and nonapproved PSMA-targeted imaging and therapeutic modalities and discusses the future of PSMA-targeted theranostics, also with an outlook on non-radiopharmaceutical-based PSMA-targeted therapies.
Substance Use, Suicidal Thoughts, and Psychiatric Comorbidities Among High School Students
Authors: Brenden Tervo-Clemmens, Jodi M. Gilman, A. Eden Evins, Kate H. Bentley, Matthew K. Nock, Jordan W. Smoller, Randi M. Schuster
Journal: JAMA Pediatrics (2024)

This cross-sectional study evaluates the dose-dependent association between alcohol, cannabis, and nicotine use and psychiatric symptoms among participants in the Substance Use and Risk Factor Survey and the Youth Risk Behavior Survey.
Immunogenicity of 2-Dose HPV Vaccine Series for Postpartum Women
Authors: Chailee F. Moss, Runzhi Wang, Saumya Sao, Betty Chou, Jamie Perin, Megan E. Lander, Sejal M. Thaker, Melindia Mann, Jenell S. Coleman
Journal: JAMA Network Open (2024)

Importance Postpartum human papillomavirus (HPV) vaccination is a promising strategy to increase HPV vaccination uptake in the US, particularly for reaching vaccine-naive women and those who lack health insurance beyond the pregnancy period. However, completion of the 3-dose vaccine regimen is challenging. Objective To evaluate the immunogenicity of a 2-dose postpartum HPV vaccination regimen (0 and 6 months) and assess whether it is noninferior to a 3-dose postpartum HPV vaccination regimen (0, 1-2, and 6 months) administered to historical controls. Design, Setting, and Participants A noninferiority, open-label, nonrandomized immunogenicity trial was conducted from August 4, 2020, to June 23, 2022, of postpartum patients aged 15 to 45 years who delivered at 2 hospitals in Baltimore, Maryland. Historical controls were adolescents and young women aged 16 to 26 years. Intervention Two doses of the nonavalent HPV vaccine administered 6 months apart. Main Outcomes and Measures The primary outcome was noninferiority (90% CI, lower bound &amp;amp;gt;0.67) of the geometric mean titer (GMT) ratio for HPV-16 among postpartum women compared with historical controls. Secondary outcomes were noninferiority of GMT ratios for the other 8 HPV types and percentage seroconversion for each HPV type. As a noninferiority trial, the primary analysis used the per-protocol analysis. Results Of 225 enrolled participants, the mean (SD) age at baseline was 29.9 (6.8) years, and 171 (76.0%) were HPV-16 seronegative at baseline. Of these 171 participants, 129 (75.4%) received a second vaccine dose and completed the subsequent 4-week serologic measurements. Relative to historical controls, the HPV-16 GMT ratio was 2.29 (90% CI, 2.03-2.58). At month 7, HPV-16 GMT was higher after the 2-dose regimen (7213.1 mMU/mL [90% CI, 6245.0-8331.4 mMU/mL]) than among historic controls after the 3-dose regimen (3154.0 mMU/mL [90% CI, 2860.2-3478.0 mMU/mL]). Similarly, the lower bound of the 90% CI of the GMT ratio was above 1 for the 8 HPV types 6, 11, 18, 31, 33, 45, 52, and 58. A total of 118 of 134 women (88.1%) seroconverted for HPV-16 after the first dose; 4 weeks after the second dose, the seroconversion rate was 99% or greater for all HPV types. Conclusions and Relevance This study suggests that immunogenicity of a 2-dose HPV vaccination regimen given 6 months apart among postpartum women was noninferior to a 3-dose regimen among young historical controls. Most women seroconverted after the first dose of the 2-dose regimen. These results demonstrate that postpartum vaccination using a reduced schedule may be a promising strategy to increase HPV vaccine series completion. Trial Registration ClinicalTrials.gov Identifier: NCT04274153
Physical Activity and Mental Health in Children and Adolescents With Neurodevelopmental Disorders
Authors: Chang Liu, Xiao Liang, Cindy H. P. Sit
Journal: JAMA Pediatrics (2024)

Children and adolescents with neurodevelopmental disorders experience mental health issues and are encouraged to be brought together in real-life treatment. However, physical activity, which is a promising method for boosting mental health, has only been examined in children and adolescents with certain types of neurodevelopmental disorders.
Is Nighttime Bracing Enough to Prevent Curve Progression of Adolescent Idiopathic Scoliosis?
Authors: Kosei Nagata
Journal: JAMA Network Open (2024)

Anastasios Charalampidis, MD, PhD; Elias Diarbakerli, PhD; Marlene Dufvenberg, MSc; Kourosh Jalalpour, MD; Acke Ohlin, MD, PhD; Anna Aspberg Ahl, MD; Hans Möller, MD, PhD; Allan Abbott, PhD; Paul Gerdhem, MD, PhD; CONTRAIS Study Group; Birgitta Öberg; Hans Tropp; Anna Grauers; Ylva Bodén; Mats Hoffsten; Per Näsman; Henrik Hedevik
Endovascular Treatment of Acute Ischemic Stroke After Cardiac Interventions in the United States
Authors: Adam de Havenon, Lily W. Zhou, Andrew B. Koo, Charles Matouk, Guido J. Falcone, Richa Sharma, John Ney, Liqi Shu, Shadi Yaghi, Hooman Kamel, Kevin N. Sheth
Journal: JAMA Neurology (2024)

Ischemic stroke is a serious complication of cardiac intervention, including surgery and percutaneous procedures. Endovascular thrombectomy (EVT) is an effective treatment for ischemic stroke and may be particularly important for cardiac intervention patients who often cannot receive intravenous thrombolysis. To examine trends in EVT for ischemic stroke during hospitalization of patients with cardiac interventions vs those without in the United States. This cohort study involved a retrospective analysis using data for 4888 US hospitals from the 2016-2020 National Inpatient Sample database. Participants included adults (age ≥18 years) with ischemic stroke (per codes from the International Statistical Classification of Diseases, Tenth Revision, Clinical Modification), who were organized into study groups of hospitalized patients with cardiac interventions vs without. Individuals were excluded from the study if they had either procedure prior to admission, EVT prior to cardiac intervention, EVT more than 3 days after admission or cardiac intervention, or endocarditis. Data were analyzed from April 2023 to October 2023. Cardiac intervention during admission. The odds of undergoing EVT by cardiac intervention status were calculated using multivariable logistic regression. Adjustments were made for stroke severity in the subgroup of patients who had a National Institutes of Health Stroke Scale (NIHSS) score documented. As a secondary outcome, the odds of discharge home by EVT status after cardiac intervention were modeled. Among 634 407 hospitalizations, the mean (SD) age of the patients was 69.8 (14.1) years, 318 363 patients (50.2%) were male, and 316 044 (49.8%) were female. A total of 12 093 had a cardiac intervention. An NIHSS score was reported in 218 576 admissions, 216 035 (34.7%) without cardiac intervention and 2541 (21.0%) with cardiac intervention (P < .001). EVT was performed in 23 660 patients (3.8%) without cardiac intervention vs 194 (1.6%) of those with cardiac intervention (P < .001). After adjustment for potential confounders, EVT was less likely to be performed in stroke patients with cardiac intervention vs those without (adjusted odds ratio [aOR], 0.27; 95% CI, 0.23-0.31), which remained consistent after adjusting for NIHSS score (aOR, 0.28; 95% CI, 0.22-0.35). Among individuals with a cardiac intervention, receiving EVT was associated with a 2-fold higher chance of discharge home (aOR, 2.21; 95% CI, 1.14-4.29). In this study, patients hospitalized with ischemic stroke and cardiac intervention may be less than half as likely to receive EVT as those without cardiac intervention. Given the known benefit of EVT, there is a need to better understand the reasons for lower rates of EVT in this patient population.
Iatrogenic Alzheimer’s disease in recipients of cadaveric pituitary-derived growth hormone
Authors: Gargi Banerjee, Simon F. Farmer, Harpreet Hyare, Zane Jaunmuktane, Simon Mead, Natalie S. Ryan, Jonathan M. Schott, David J. Werring, Peter Rudge, John Collinge
Journal: Nature Medicine (2024)

Abstract Alzheimer’s disease (AD) is characterized pathologically by amyloid-beta (Aβ) deposition in brain parenchyma and blood vessels (as cerebral amyloid angiopathy (CAA)) and by neurofibrillary tangles of hyperphosphorylated tau. Compelling genetic and biomarker evidence supports Aβ as the root cause of AD. We previously reported human transmission of Aβ pathology and CAA in relatively young adults who had died of iatrogenic Creutzfeldt–Jakob disease (iCJD) after childhood treatment with cadaver-derived pituitary growth hormone (c-hGH) contaminated with both CJD prions and Aβ seeds. This raised the possibility that c-hGH recipients who did not die from iCJD may eventually develop AD. Here we describe recipients who developed dementia and biomarker changes within the phenotypic spectrum of AD, suggesting that AD, like CJD, has environmentally acquired (iatrogenic) forms as well as late-onset sporadic and early-onset inherited forms. Although iatrogenic AD may be rare, and there is no suggestion that Aβ can be transmitted between individuals in activities of daily life, its recognition emphasizes the need to review measures to prevent accidental transmissions via other medical and surgical procedures. As propagating Aβ assemblies may exhibit structural diversity akin to conventional prions, it is possible that therapeutic strategies targeting disease-related assemblies may lead to selection of minor components and development of resistance.
Definitional and Methodological Errors in Pediatric Post–COVID-19 Condition Research Letter—Reply
Authors: Lyndsey Hahn, Joan Robinson, Piush J. Mandhane
Journal: JAMA Pediatrics (2024)

In Reply We thank Murdoch et al for their interest in our pediatric post–COVID-19 condition (PCC) research.1 Contrary to their suggestion, we believe our work is consistent with the referenced 20222 and 20233 World Health Organization (WHO) definitions of PCC.
Trends in Out-of-Pocket Costs for and Characteristics of Pharmacy-Dispensed Naloxone by Payer Type
Authors: Xinyi Jiang, Andrea E. Strahan, Kun Zhang, Gery P. Guy
Journal: JAMA (2024)

This study examines mean yearly out-of-pocket cost for naloxone dispensed from retail pharmacies by payer between 2018 and 2022 and by prescription characteristics and payer in 2022.
Cluster randomised controlled trial of specialist-led integrated COPD care (INTEGR COPD)
Authors: Ketan Patel, Anita Pye, Ross G Edgar, Helen Beadle, Paul R Ellis, Alice Sitch, Andrew P Dickens, Alice M Turner
Journal: Thorax (2024)

Objective Studies in hospital settings demonstrate that there is greater guideline adherence when care is delivered by a respiratory specialist, however, this has not been explored in primary care. The aim of this study is to determine the impact integrating respiratory specialists into primary care has on the delivery of guideline adherent chronic obstructive pulmonary disease (COPD) care. Methods 18 general practitioner (GP) practices were randomised to provide either usual or specialist-led COPD care. Patients at participating practices were included if they had an existing diagnosis of COPD. Outcomes were measured at the individual patient level. The primary outcome was guideline adherence, assessed as achieving four or more items of the COPD care bundle. Secondary outcome measures included quality of life, number of exacerbations, number of COPD-related hospitalisations and respiratory outpatient attendances. Results 586 patients from 10 practices randomised to the intervention and 656 patients from 8 practices randomised to the control arm of the study were included. The integration of respiratory specialists into GP practices led to a statistically significant (p&lt;0.001) improvement in the provision of guideline adherent care when compared with usual care in this cohort (92.7% vs 70.1%) (OR 4.14, 95% CI 2.14 to 8.03). Conclusion This is the first study to demonstrate that guideline adherence is improved through the integration of respiratory specialists into GP practices to deliver annual COPD reviews. To facilitate changes in current healthcare practice and policy, the findings of this paper need to be viewed in combination with qualitative research exploring the acceptability of specialist integration. Trial registration number NCT03482700 .
Definitional and Methodological Errors in Pediatric Post–COVID-19 Condition Research Letter
Authors: Blake Murdoch, Malgorzata Gasperowicz, Mark Ungrin
Journal: JAMA Pediatrics (2024)

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Ketamine Compared With Morphine for Out-of-Hospital Analgesia for Patients With Traumatic Pain
Authors: Clément Le Cornec, Marion Le Pottier, Hélène Broch, Alexandre Marguinaud Tixier, Emmanuel Rousseau, Said Laribi, Charles Janière, Vivien Brenckmann, Anne Guillerm, Florence Deciron, Amine Kabbaj, Joël Jenvrin, Morgane Péré, Emmanuel Montassier
Journal: JAMA Network Open (2024)

Importance Pain is a common out-of-hospital symptom among patients, and opioids are often prescribed. Research suggests that overprescribing for acute traumatic pain is still prevalent, even when limits restricting opioid prescriptions have been implemented. Ketamine hydrochloride is an alternative to opioids in adults with out-of-hospital traumatic pain. Objective To assess the noninferiority of intravenous ketamine compared with intravenous morphine sulfate to provide pain relief in adults with out-of-hospital traumatic pain. Design, Setting, and Participants The Intravenous Subdissociative-Dose Ketamine Versus Morphine for Prehospital Analgesia (KETAMORPH) study was a multicenter, single-blind, noninferiority randomized clinical trial comparing ketamine hydrochloride (20 mg, followed by 10 mg every 5 minutes) with morphine sulfate (2 or 3 mg every 5 minutes) in adult patients with out-of-hospital trauma and a verbal pain score equal to or greater than 5. Enrollment occurred from November 23, 2017, to November 26, 2022, in 11 French out-of-hospital emergency medical units. Interventions Patients were randomly assigned to ketamine (n = 128) or morphine (n = 123). Main Outcomes and Measures The primary outcome was the between-group difference in mean change in verbal rating scale pain scores measured from the time before administration of the study drug to 30 minutes later. A noninferiority margin of 1.3 was chosen. Results A total of 251 patients were randomized (median age, 51 [IQR, 34-69] years; 111 women [44.9%] and 140 men [55.1%] among the 247 with data available) and were included in the intention-to-treat population. The mean pain score change was −3.7 (95% CI, −4.2 to −3.2) in the ketamine group compared with −3.8 (95% CI, −4.2 to −3.4) in the morphine group. The difference in mean pain score change was 0.1 (95% CI, −0.7 to 0.9) points. There were no clinically meaningful differences for vital signs between the 2 groups. The intravenous morphine group had 19 of 113 (16.8% [95% CI, 10.4%-25.0%]) adverse effects reported (most commonly nausea [12 of 113 (10.6%)]) compared with 49 of 120 (40.8% [95% CI, 32.0%-49.6%]) in the ketamine group (most commonly emergence phenomenon [24 of 120 (20.0%)]). No adverse events required intervention. Conclusions and Relevance In the KETAMORPH study of patients with out-of-hospital traumatic pain, the use of intravenous ketamine compared with morphine showed noninferiority for pain reduction. In the ongoing opioid crisis, ketamine administered alone is an alternative to opioids in adults with out-of-hospital traumatic pain. Trial Registration ClinicalTrials.gov Identifier: NCT03236805
Multiomic Analysis of Neuroinflammation and Occult Infection in Sudden Infant Death Syndrome
Authors: Prashanth S. Ramachandran, Benjamin W. Okaty, Molly Riehs, Anne Wapniarski, Daniel Hershey, Hani Harb, Maham Zia, Elisabeth A. Haas, Sanda Alexandrescu, Lynn A. Sleeper, Sara O. Vargas, Mark P. Gorman, Steven Campman, Othon J. Mena, Keith Levert, Keith Hyland, Richard D. Goldstein, Michael R. Wilson, Robin L. Haynes
Journal: JAMA Neurology (2024)

Antemortem infection is a risk factor for sudden infant death syndrome (SIDS)-the leading postneonatal cause of infant mortality in the developed world. Manifestations of infection and inflammation are not always apparent in clinical settings or by standard autopsy; thus, enhanced resolution approaches are needed.
Changes in Homelessness Among US Veterans After Implementation of the Ending Veteran Homelessness Initiative
Authors: Thomas P. O’Toole, Lisa M. Pape, Vincent Kane, Monica Diaz, Anne Dunn, James L. Rudolph, Shereef Elnahal
Journal: JAMA Network Open (2024)

Homelessness is a persistent and growing problem. What role health systems should play and how that role is incorporated into larger strategic efforts are not well-defined. To compare homelessness among veterans with that in the general population during a 16-year study period before and after implementation of the Ending Veteran Homelessness Initiative, a program to rehouse veterans experiencing homelessness. This national retrospective cohort study using a mixed-methods approach examined annualized administrative (January 1, 2007, to December 31, 2022) and population data prior to (2007-2009) and during (2010-2022) the Ending Veteran Homelessness initiative. Participants included unhoused adults in the US between 2007 and 2022. Enrollment in Veterans Health Administration (VHA) Homeless Program Office components providing housing, case management, and wrap-around clinical and supportive services. Point-in-time (PIT) count data for unhoused veterans and nonveterans during the study period, number of Section 8 housing vouchers provided by Housing and Urban Development-Veterans Administration Supportive Housing, number of community grants awarded by Supportive Services for Veterans and Families, and total number of veterans housed each year. Semistructured interviews with VHA leadership were performed to gain insight into the strategy. In 2022, 33 129 veterans were identified in the PIT count. They were predominantly male (88.7%), and 40.9% were unsheltered. During the active years of the Ending Veteran Homelessness initiative, veteran homelessness decreased 55.3% compared with 8.6% for the general population. The proportion of veterans in this cohort also declined from 11.6% to 5.3%. This change occurred during a shift to "housing first" as agency policy to create low-barrier housing availability. It was also coupled with substantial growth in housing vouchers, grants to community partner agencies, and growth in VHA clinical and social programming to provide homeless-tailored wrap-around services and support once participants were housed. Key respondent interviews consistently cited the shift to housing first, the engagement with community partners, and use of real-time data as critical. In this cohort study of the federal Ending Veteran Homelessness initiative, after program implementation, there was a substantially greater decrease in homelessness among veterans than in the general population. These findings suggest an important role for health systems in addressing complex social determinants of health. While some conditions unique to the VHA facilitated the change in homelessness, lessons learned here are applicable to other health systems.
Injury incidence according to athlete impairment type during the 2012 and 2016 Summer Paralympic Games: a combined analysis of 101 108 athlete days
Authors: Faatima Adam, Wayne Derman, Martin Schwellnus, Pieter-Henk Boer, Esme Jordaan, Phoebe Runciman
Journal: British Journal of Sports Medicine (2024)

Objectives The relationship between sport-related injuries and Para athlete impairment type has not yet been comprehensively studied. This study aimed to describe injury incidence according to athlete impairment type during the London 2012 and Rio 2016 Summer Paralympic Games, by sex, age, Games period, chronicity and anatomical area. Methods A combined analysis of 7222 athletes was conducted comprising 101 108 athlete days, using pooled data. Internet sources were used to identify impairments of registered athletes. Impairment types: brain disorders (BD), limb deficiency, neuromuscular disorders (NMD), spinal cord-related disorders, visual impairment (VI) and ‘all others’ (OTH: impaired passive range of movement, intellectual impairment, leg length difference, short stature and unknown impairments). Results by impairment type are reported as univariate unadjusted incidences (injuries/1000 athlete days; 95% CIs). Statistical significance between impairment types was determined when 95% CIs did not overlap. Results The overall crude unadjusted incidence of injury was 11.1 (95% CI 10.4 to 11.9), significantly higher in VI (13.7 (95% CI 11.0 to 15.7)) and NMD (13.3 (95% CI 11.1 to 16.1)) compared with BD (9.1 (95% CI 7.7 to 10.8)). Acute (sudden onset) (8.6 (95% CI 7.3 to 10.1)) and lower limb (6.6 (95% CI 5.4 to 8.1)) injuries were higher among athletes with VI, while athletes with NMD had a higher incidence of repetitive (gradual onset) (5.9 (95% CI 4.3 to 8.0)) and upper limb (6.9 (95% CI 5.2 to 9.0)) injuries compared with other impairments. Conclusions Incidence and type of injuries differed between athlete impairment types. Athletes with VI or NMD sustained the highest incidence of injury, and athletes with BD had the lowest. Findings of this study can inform the management of competition-related injuries in Para athletes.