tbuckley/cabot-search huggingface dataset:
Hearing Loss, Incident Parkinson Disease, and Treatment With Hearing Aids
Authors: Lee E. Neilson, Kelly M. Reavis, Jack Wiedrick, Gregory D. Scott
Journal: JAMA Neurology (2024)

Importance The risk of developing Parkinson disease (PD) after objective hearing loss is unknown. PD studies using self-reported hearing loss are insensitive, and objective data are lacking. Objective To examine the association of hearing loss with incident PD in US veterans and its effect modification by well-established prodromal conditions and hearing aids. Design, Setting, and Participants This cohort study analyzed electronic health record data from the US Department of Veterans Affairs for veterans who had an audiogram from January 1, 1999, to December 30, 2022. Individuals with data missing or a preexisting PD diagnosis were excluded. Exposure Audiogram-confirmed hearing loss. Main Outcomes and Measures Cumulative incidence of PD was calculated with adjustment for competing risk of death. Results Among 7 296 051 veterans with an audiogram, 3 596 365 were included. They were mostly male (n = 3 452 898 [96%]) and had a mean (SD) age of 67 (10.3) years. A total of 750 010 individuals (20.8%) had normal hearing at the time of audiometry examination; among those with hearing loss, 1 080 651 (30.0%), 1 039 785 (28.9%), 568 296 (15.8%), and 157 623 (4.3%) individuals had mild (20-&amp;amp;lt;35 dB), moderate (35-&amp;amp;lt;50 dB), moderate to severe (50-&amp;amp;lt;65 dB), and severe to profound (65-120 dB) hearing loss, respectively. Age, gender, and smoking history were balanced between all exposed and unexposed groups with further adjustment for race, ethnicity, and frailty. At 10 years after the baseline audiogram, the numbers of additional cases of PD were 6.1 (95% CI, 4.5-7.79, 15.8 (95% CI, 12.8-18.8), 16.2 (95% CI, 11.9-20.6), and 12.1 (95% CI, 4.5-19.6) among veterans with mild, moderate, moderate to severe, and severe to profound hearing loss, respectively, compared with those with normal hearing. When combined with established prodromal conditions, hearing loss was associated with 5.7 (95% CI, 2.2-9.2) additional cases of PD at 10 years compared with either condition alone. With prompt hearing aid dispensation, incident cases of PD decreased by 21.6 cases (95% CI, 19.5-23.6) at 10 years. Conclusions and Relevance Hearing loss appears to be an independent risk factor for later development of PD. Hearing aids attenuate this risk, and therefore widespread screening for hearing loss and appropriate use of hearing aids may reduce the incidence of PD. Additional studies are needed to examine the mechanisms underlying the association between hearing loss and PD.
Strategies to Help Patients Navigate High Prescription Drug Costs
Authors: Hussain S. Lalani, Catherine S. Hwang, Aaron S. Kesselheim, Benjamin N. Rome
Journal: JAMA (2024)

In the US, many patients struggle to afford prescription drugs, leading to adverse health outcomes. To improve cost-related medication nonadherence, prescribers and clinical staff must understand how to assist patients in overcoming high prescription drug costs.
Prevalence of Hearing Loss and Hearing Aid Use Among Persons Living With Dementia in the US
Authors: Carrie L. Nieman, Emmanuel E. Garcia Morales, Alison R. Huang, Nicholas S. Reed, Sevil Yasar, Esther S. Oh
Journal: JAMA Network Open (2024)

Importance Dementia and hearing loss are prevalent and represent public health priorities, but little is known about the prevalence of hearing loss among persons living with dementia at a population level. Objective To estimate the prevalence of hearing loss and hearing aid use among a nationally representative sample of persons living with dementia. Design, Setting, and Participants In this cross-sectional study, we analyzed data from Medicare beneficiaries who participated in round 11 of the National Health and Aging Trends Study (NHATS). The analytic sample included participants who had complete audiometric data and a dementia classification, and survey weights were applied to yield nationally representative estimates. Data were collected from June to November 2021, and analyzed from October 12, 2023, to February 27, 2024. Exposures Audiometric measures of hearing loss and self-reported hearing aid use. Main Outcomes and Measures National prevalence estimates of possible and probable dementia and hearing loss were estimated by applying NHATS survey weights of sex and age to the population aged 71 years or older based on the US Census Bureau’s 2020 American Community Survey data. Results The analytic sample comprised 2613 NHATS participants (74.6% aged 71-79 years and 25.4% aged ≥80 years; 52.9% female). Overall prevalence of hearing loss among participants with dementia was estimated at 79.4% (95% CI, 72.1%-85.3%). The prevalence of hearing loss increased with age, from 61.1% (95% CI, 37.7%-80.2%) among participants aged 71 to 74 years to 94.2% (95% CI, 88.8%-97.0%) among those aged 85 years or older. Among participants with hearing loss, 21.7% (95% CI, 16.2%-28.3%) reported hearing aid use. Conclusions and Relevance In this cross-sectional study, the findings suggest that hearing loss is highly prevalent among individuals with dementia, with a low prevalence of hearing aid use. These findings reveal a potential opportunity for intervention.
Risk of Inflammatory Central Nervous System Diseases After Tumor Necrosis Factor–Inhibitor Treatment for Autoimmune Diseases
Authors: Wenhui Xie, Yunchuang Sun, Wei Zhang, Nanbo Zhu, Shiyu Xiao
Journal: JAMA Neurology (2024)

Importance Tumor necrosis factor (TNF) inhibitors have been used extensively to treat various autoimmune diseases. However, there are ongoing debates about the risk of inflammatory central nervous system (CNS) disease events following TNF inhibitor therapy, as well as uncertainty about how this risk varies across different autoimmune diseases or TNF-blocking agents. Objective To evaluate the risk of inflammatory CNS diseases after anti-TNF initiation and assess the difference in risk among different types of underlying autoimmune diseases or TNF inhibitors. Data Sources Separate searches were conducted across PubMed, Embase, and the Cochrane Library from inception until March 1, 2024. Study Selection Observational studies assessing the association between anti-TNF therapy and inflammatory CNS diseases relative to a comparator group. Data Extraction and Synthesis Study eligibility assessment and data extraction were independently conducted by 2 investigators following PRISMA guidelines. The risk ratio (RR) was used as the effect measure of the pooled analysis. Main Outcomes and Measures The primary outcome was the risk of incident inflammatory CNS events after anti-TNF therapy for autoimmune diseases. Secondary analyses were performed based on different types of underlying autoimmune diseases and TNF inhibitors. Results Eighteen studies involving 1 118 428 patients with autoimmune diseases contributing more than 5 698 532 person-years of follow-up were analyzed. The incidence rates of new-onset inflammatory CNS events after initiating TNF inhibitors ranged from 2.0 to 13.4 per 10 000 person-years. Overall, exposure to TNF inhibitors was associated with a 36% increased risk of any inflammatory CNS disease compared to conventional therapies (RR, 1.36; 95% CI, 1.01-1.84; I 2 , 49%), mainly attributed to demyelinating diseases (RR, 1.38; 95% CI, 1.04-1.81; I 2 , 31%). Secondary analyses revealed a similar risk of inflammatory CNS diseases across different types of underlying autoimmune diseases (rheumatic diseases: RR, 1.36; 95% CI, 0.84-2.21; inflammatory bowel disease 1.49; 95% CI, 0.93-2.40; P for subgroup = .74) and TNF inhibitors (anti-TNF monoclonal antibodies vs etanercept: RR, 1.04; 95% CI, 0.93-1.15; I 2 , 0%). Conclusions and Relevance Compared to conventional therapies, exposure to TNF inhibitors was associated with a 36% increased risk of inflammatory CNS diseases, irrespective of background autoimmune disease or TNF inhibitor type.
Trends in Cancer Incidence and Potential Associated Factors in China
Authors: Mandi Li, Meijing Hu, Lin Jiang, Jiao Pei, Cairong Zhu
Journal: JAMA Network Open (2024)

Importance Timely analysis of cancer incidence trends is crucial for cancer prevention and control, which is a public health priority in China. Objective To estimate incidence trends for 32 cancers in China from 1983 to 2017 and project changes to 2032, assessing distinct changes due to risk factors and an aging population. Design, Setting, and Participants This population-based cohort study used data from the Cancer Incidence in Five Continents database (1983-2017). New cases of 32 cancers were collected. Data were analyzed from October 15, 2023, to May 23, 2024. Main Outcomes and Measures Age-standardized incidence rate (AIR) standardized to the World Health Organization World Standard Population, average annual percentage changes (AAPC) using joinpoint regression, and percentage change due to aging and risk factors, using Møller decomposition analysis, stratified by cancer and sex. Results A total of 3 677 027 new cancer cases (54.9% male, 45.1% female) were included in the analysis. Increased AIRS were observed for 11 cancers in males and 14 in females from 1983 to 2017, with trends expected to continue until 2032. Thyroid cancer showed the highest increase (AAPC: 7.82% in males; 95% CI, 6.92%-10.38%; 8.59% in females; 95% CI, 7.84%-10.42%), followed by prostate (4.71%; 95% CI, 3.12%-9.95%) and kidney (3.61%; 95% CI, 3.11%-5.82%) cancers in males, and cervical (4.43%; 95% CI, 3.36%-9.44%) and kidney (3.66%; 95% CI, 2.98%-6.86%) cancers in females. The AIRs of lung cancer tended to decrease in males but increase in females during 1983-2017. In contrast, the AIRs of stomach, liver, larynx, and nose and sinuses cancers decreased from 1983 to 2032. From 2018 to 2032, cancer cases were projected to increase primarily due to risk factors for 18 cancers in males and 11 in females, while aging would be associated with the increase in other cancers. Conclusions and Relevance In this population-based cohort study of incident cancer in the general population, the cancer landscape in China is evolving, with an increasing incidence primarily due to risk factors in 20 cancers and aging in others. Primary prevention efforts to reduce risk exposure are crucial, and further basic research is needed. Additionally, second prevention efforts are imperative to improve cancer survival, particularly among older individuals.
Genome Sequencing After Exome Sequencing in Pediatric Epilepsy
Authors: Alissa M. D’Gama, Wanqing Shao, Lacey Smith, Hyun Yong Koh, Maya Davis, Julia Koh, Brandon T. Oby, Cesar I. Urzua, Beth Rosen Sheidley, Shira Rockowitz, Annapurna Poduri
Journal: JAMA Neurology (2024)

This cohort study examined the yield and use of genome sequencing after nondiagnostic exome sequencing for pediatric patients with unexplained epilepsy between August 2018 and May 2023.
High-Risk Medications in Persons Living With Dementia
Authors: Sonal Singh, Xiaojuan Li, Noelle M. Cocoros, Mary T. Antonelli, Ramya Avula, Sybil L. Crawford, Inna Dashevsky, Hassan Fouayzi, Thomas P. Harkins, Kathleen M. Mazor, Ashley I. Michnick, Lauren Parlett, Mark Paullin, Richard Platt, Paula A. Rochon, Cassandra Saphirak, Mia Si, Yunping Zhou, Jerry H. Gurwitz
Journal: JAMA Internal Medicine (2024)

Importance Individuals with Alzheimer disease (AD) and Alzheimer disease–related dementias (ADRD) may be at increased risk for adverse outcomes relating to inappropriate prescribing of certain high-risk medications, including antipsychotics, sedative-hypnotics, and strong anticholinergic agents. Objective To evaluate the effect of a patient/caregiver and prescriber-mailed educational intervention on potentially inappropriate prescribing to patients with AD or ADRD. Design, Setting, and Participants This prospective, open-label, pragmatic randomized clinical trial, embedded in 2 large national health plans, was conducted from April 2022 to June 2023. The trial included patients with AD or ADRD and use of any of 3 drug classes targeted for deprescribing (antipsychotics, sedative-hypnotics, or strong anticholinergics). Interventions Patients were randomized to 1 of 3 arms: (1) a mailing of educational materials specific to the medication targeted for deprescribing to both the patient and their prescribing clinician; (2) a mailing to the prescribing clinician only; or (3) a usual care arm. Main Outcomes and Measures Analysis was performed using a modified intention-to-treat approach. The primary study outcome was the dispensing of the medication targeted for deprescribing during a 6-month study observation period. Secondary outcomes included changes in medication-specific mean daily dose and health service utilization. Results Among 12 787 patients included in the modified intention-to-treat analysis, 8742 (68.4%) were female, and the mean (SD) age was 77.3 (9.4) years. The cumulative incidence of being dispensed a medication targeted for deprescribing was 76.7% (95% CI, 75.4-78.0) in the patient and prescriber mailing group, 77.9% (95% CI, 76.5-79.1) in the prescriber mailing only group, and 77.5% (95% CI, 76.2-78.8) in the usual care group. Hazard ratios were 0.99 (95% CI, 0.94-1.04) for the patient and prescriber group and 1.00 (95% CI, 0.96-1.06) for the prescriber only group compared with the usual care group. There were no differences between the groups for secondary outcomes. Conclusions and Relevance These findings suggest medication-specific educational mailings targeting patients with AD or ADRD and their clinicians are not effective in reducing the use of high-risk medications. Trial Registration ClinicalTrials.gov Identifier: NCT05147428
Recurrent Respiratory Papillomatosis in the Post–Human Papillomavirus Vaccination Era
Authors: Z. Jason Qian, Daniel Peñaranda, Tulio A. Valdez, Karthik Balakrishnan, Matthew T. Brigger
Journal: JAMA Pediatrics (2024)

This cross-sectional study examines the incidence of juvenile-onset recurrent respiratory papillomatosis and HPV vaccination rates from 2007 to 2022 in the US.
Community Health Workers Linking Clinics and Schools and Asthma Control
Authors: Tyra Bryant-Stephens, Chen C. Kenyon, Colleen Tingey, Andrea Apter, Julie Pappas, Natalie Minto, Yvonne S. Stewart, Justine Shults
Journal: JAMA Pediatrics (2024)

Importance Childhood asthma is characterized by pervasive disparities, including 3-fold higher hospitalization rates and 7-fold higher death rates for Black children compared with White children. To address asthma disparities, one must intervene in all lived environments. Objective To determine if a community health worker (CHW) intervention to connect the primary care, home, and school for low-income minoritized school-aged children with asthma and their caregivers improves asthma control. Design, Setting, and Participants This study was a hybrid effectiveness/implementation trial using a 2 × 2 factorial, cluster randomized clinical trial design of 36 schools crossed with participant-level randomization into a clinic-based CHW intervention. The study was conducted from May 2018 to June 2022. The intervention took place in primary care offices, homes, and 36 West Philadelphia, Pennsylvania, public and charter schools. Children aged 5 to 13 years with uncontrolled asthma were recruited from local primary care practices. Interventions Asthma management, trigger remediation, and care coordination occurred in school, home, and primary care settings. Children were followed up for 12 months. The Yes We Can Children’s Asthma Program, Open Airways For Schools Plus, and school-based asthma therapy were implemented. Main Outcomes and Measures Improvement in asthma control, as measured by the Asthma Control Questionnaire, comparing the mean difference between groups 1 year after randomization with their baseline (difference in differences). Both primary care and school interventions were dramatically disrupted by the COVID-19 pandemic; therefore, stratified analyses were performed to assess per-protocol intervention efficacy before the pandemic disruptions. Results A total of 1875 participants were approached, 1248 were excluded, and 1 was withdrawn. The 626 analyzed study participants (mean [SD] age, 8.7 [2.4] years; 363 male [58%]) self-identified as Black race (96%) and non-Hispanic ethnicity (98%). Although all groups had statistically significant improvements in asthma control from baseline to 12 months (P− group: −0.46; 95% CI, −0.58 to −0.33; P+ group: −0.57; 95% CI, −0.74 to −0.44; S− group: −0.47; 95% CI, −0.58 to −0.35; S+ group: −0.59; 95% CI, −0.74 to −0.44), none of the difference-in-differences estimates from the primary prespecified models showed a clinically meaningful improvement in asthma control. Analysis from the prepandemic interval, however, demonstrated that children in the combined clinic-school intervention had a statistically significant improvement in asthma control scores compared with control (−0.79; 95% CI, −1.40 to −0.18). Conclusions and Relevance This randomized clinical trial provides preliminary evidence that connecting all lived environments for care of children can be accomplished through linkages with CHWs.
Amyloid-β (Aβ) immunotherapy induced microhemorrhages are linked to vascular inflammation and cerebrovascular damage in a mouse model of Alzheimer’s disease
Authors: Xavier Taylor, Harun N. Noristani, Griffin J. Fitzgerald, Herold Oluoch, Nick Babb, Tyler McGathey, Lindsay Carter, Justin T. Hole, Pascale N. Lacor, Ronald B. DeMattos, Yaming Wang
Journal: Molecular Neurodegeneration (2024)

Abstract Background Anti-amyloid-β (Aβ) immunotherapy trials have revealed amyloid-related imaging abnormalities (ARIA) as the most prevalent and serious adverse events linked to pathological changes in cerebral vasculature. Recent studies underscore the critical involvement of perivascular macrophages and the infiltration of peripheral immune cells in regulating cerebrovascular damage. Specifically, Aβ antibodies engaged at cerebral amyloid angiopathy (CAA) deposits trigger perivascular macrophage activation and the upregulation of genes associated with vascular permeability. Nevertheless, further research is needed to understand the immediate downstream consequences of macrophage activation, potentially exacerbating CAA-related vascular permeability and microhemorrhages linked to Aβ immunotherapy. Methods This study investigates immune responses induced by amyloid-targeting antibodies and CAA-induced microhemorrhages using RNA in situ hybridization, histology and digital spatial profiling in an Alzheimer's disease (AD) mouse model of microhemorrhage. Results In the present study, we have demonstrated that bapineuzumab murine surrogate (3D6) induces profound vascular damage, leading to smooth muscle cell loss and blood–brain barrier (BBB) breakdown. In addition, digital spatial profiling (DSP) reveals that distinct immune responses contribute to vascular damage with peripheral immune responses and perivascular macrophage activation linked to smooth muscle cell loss and vascular fibrosis, respectively. Finally, RNA in situ hybridization identifies two distinct subsets of Trem2 + macrophages representing tissue-resident and monocyte-derived macrophages around vascular amyloid deposits. Overall, these findings highlight multifaceted roles of immune activation and vascular damage in driving the development of microhemorrhage. Conclusions In summary, our study has established a significant link between CAA-Aβ antibody immune complex formation, immune activation and vascular damage leading to smooth muscle cell loss. However, the full implications of this cascade on the development of microhemorrhages requires further exploration. Additional investigations are warranted to unravel the precise molecular mechanisms leading to microhemorrhage, the interplay of diverse immune populations and the functional roles played by various Trem2 + macrophage populations in response to Aβ immunotherapy.
Chinese Expert Consensus on the Combination of Targeted Therapy and Immunotherapy with Locoregional Therapy for Intermediate/Advanced Hepatocellular Carcinoma
Authors: Xinyu Bi, Yinying Lu, Bo Chen, Zhengqiang Yang, Zhixian Hong, Hanping Wang, Yongkun Sun, Xiaodong Wang, Chunwang Yuan, Daobing Zeng, Zhen Huang, Aiping Zhou, Wen Zhang, Shunda Du, Jianjun Zhao, Jianguo Zhou, Yirui Zhai, Xu Che, Hong Zhao, Haitao Zhao, Jianqiang Cai
Journal: Liver Cancer (2024)

Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality; it ranks as the second most common cause of cancer deaths in China. Most HCC patients are first diagnosed at an advanced stage. In recent years, targeted therapy combined with immunotherapy has become the preferred regimen for systemic treatment of intermediate-advanced HCC, while targeted therapy combined with immunotherapy plus local treatment could further improve the efficacy in many clinical studies. To better guide the clinical treatment for effective and safe combination therapy, our interdisciplinary panel on the treatment of intermediate-advanced HCC comprising hepatologists, hepatobiliary surgeons, oncologists, radiologists, interventional radiologists, and traditional Chinese medicine physicians have formulated this consensus based on current clinical studies and clinical medication experience for reference. The consensus contained 15 recommendations, including the applicable population and management, local treatment selection, conversion strategy, treatment strategy after tumor progression and management of common adverse reactions.
Meeting the Unmet Needs in Rare Cancer
Authors: Ning Li, Shuhang Wang, Guo Zhao
Journal: JAMA (2024)

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Response to Comment on Hsieh et al. COVID-19 Vaccination Prior to SARS-CoV-2 Infection Reduced Risk of Subsequent Diabetes Mellitus: A Real-World Investigation Using U.S. Electronic Health Records. Diabetes Care 2023;46:2193–2200
Authors: Tina Y.I. Jin Hsieh, Renin Chang, Su-Boon Yong, Pei-Lun Liao, Yao-Min Hung, James Cheng-Chung Wei
Journal: Diabetes Care (2024)