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Abstract Background Post-acute sequelae of SARS-CoV-2 infection (PASC) symptoms have broad impact, and may affect individuals regardless of COVID-19 severity, socioeconomic status, race, ethnicity, or age. A prominent PASC symptom is cognitive dysfunction, colloquially referred to as “brain fog” and characterized by declines in short-term memory, attention, and concentration. Cognitive dysfunction can severely impair quality of life by impairing daily functional skills and preventing timely return to work. Methods RECOVER-NEURO is a prospective, multi-center, multi-arm, phase 2, randomized, active-comparator design investigating 3 interventions: (1) BrainHQ is an interactive, online cognitive training program; (2) PASC-Cognitive Recovery is a cognitive rehabilitation program specifically designed to target frequently reported challenges among individuals with brain fog; (3) transcranial direct current stimulation (tDCS) is a noninvasive form of mild electrical brain stimulation. The interventions will be combined to establish 5 arms: (1) BrainHQ; (2) BrainHQ + PASC-Cognitive Recovery; (3) BrainHQ + tDCS-active; (4) BrainHQ + tDCS-sham; and (5) Active Comparator. The interventions will occur for 10 weeks. Assessments will be completed at baseline and at the end of intervention and will include cognitive testing and patient-reported surveys. All study activities can be delivered in Spanish and English. Discussion This study is designed to test whether cognitive dysfunction symptoms can be alleviated by the use of pragmatic and established interventions with different mechanisms of action and with prior evidence of improving cognitive function in patients with neurocognitive disorder. If successful, results will provide beneficial treatments for PASC-related cognitive dysfunction. Trial registration ClinicalTrials.gov NCT05965739. Registered on July 25, 2023.

Background and Aims: Gastric cancer (GC) is a leading cause of cancer incidence and mortality globally. Population screening is limited by the low incidence and prevalence of GC in the United States. A risk prediction algorithm to identify high-risk patients allows for targeted GC screening. We aimed to determine the feasibility and performance of a logistic regression model based on electronic health records to identify individuals at high risk for noncardia gastric cancer (NCGC). Methods: We included 614 patients who had a diagnosis of NCGC between ages 40 and 80 years and who were seen at our large tertiary medical center in multiple states between 2010 and 2021. Controls without a diagnosis of NCGC were randomly selected in a 1:10 ratio of cases to controls. Multiple imputation by chained equations for missing data followed by logistic regression on imputed datasets was used to estimate the probability of NCGC. Area under the curve and the 0.632 estimator was used as the estimate for discrimination. Results: The 0.632 estimator value was 0.731, indicating robust model performance. Probability of NCGC was higher with increasing age (odds ratio [OR] = 1.16, 95% confidence interval [CI]: 1.04–1.3), male sex (OR = 1.97; 95% CI: 1.64–2.36), Black (OR = 3.07; 95% CI: 2.46–3.83) or Asian race (OR = 4.39; 95% CI: 2.60–7.42), tobacco use (OR = 1.61; 95% CI: 1.34–1.94), anemia (OR = 1.35; 95% CI: 1.09–1.68), and pernicious anemia (OR = 6.12, 95% CI: 3.42–10.95). Conclusion: We demonstrate the feasibility and good performance of an electronic health record–based logistic regression model for estimating the probability of NCGC. Future studies will refine and validate this model, ultimately identifying a high-risk cohort who could be eligible for NCGC screening.

Background: Hereditary angioedema with C1-inhibitor deficiency (HAE-C1INH) is a rare autosomal disorder presenting with recurrent angioedema. Estrogen-containing medications trigger angioedema in some patients, and conversely, progesterone may decrease attack frequency. The mechanism by which estrogen may exacerbate angioedema in HAE-C1INH is not well characterized. Objective: Our aim was to investigate the link between estrogen and bradykinin constituents to better understand the specific underlying triggers that may exacerbate angioedema in patients with HAE-C1INH. Methods: As estrogen is contraindicated for patients with HAE-C1INH, females without a history of angioedema were recruited to evaluate whether estrogen-containing oral contraceptive pills (OCPs) alter plasma protein levels of bradykinin, cleaved high-molecular-weight kininogen (cHK), and activated factor XII (FXIIa). Blood (plasma) was collected before initiation of OCP administration and 3 months thereafter. High-molecular-weight kininogen (HK) was measured by ELISA and FXIIa and cHK were analyzed by Western blot analysis. Results: A total of 12 adult females without HAE-CINH (aged

Introduction: Individuals with a history of smoking and a high risk of lung cancer often have a high prevalence of smoking-related comorbidities. The presence of these comorbidities might alter the benefit-to-harm ratio of lung cancer screening by influencing the risk of complications, quality of life, and competing risks of death. Nevertheless, individuals with chronic diseases are underrepresented in screening clinical trials. In this study, we use microsimulation modeling to determine the impact of chronic diseases on lung cancer benefits and harms. Methods: We extended a validated lung cancer screening microsimulation model that comprehensively recapitulates an individual’s lung cancer development, progression, detection, follow-up, treatment, and survival. We parameterized the model to reflect the impact of chronic diseases on complications from invasive testing, quality of life, and mortality in individuals in five-year age categories between the ages of 50 and 80 years. Outcomes included life-years (LY) gained per 100,000 in patients with chronic obstructive pulmonary disease, diabetes mellitus, heart disease, and history of stroke compared with screening-eligible individuals without comorbidities. Results: Among individuals between the ages of 50 and 54 years, we found that the presence of a comorbidity altered the LY gained from screening per 100,000 individuals depending on the comorbidity: 4296 LY with no comorbidities; 3462 LY, 3260 LY, 3031 LY, and 3257 LY with chronic obstructive pulmonary disease, heart disease, diabetes mellitus, and stroke, respectively. We observed greater reductions in LY gained in individuals with two comorbidities; we observed similar patterns for individuals between the ages of 55 and 59 years, 60 and 64 years, 65 and 69 years, 70 and 74 years, and 75 and 80 years. Conclusions: Comorbidities reduce LY gained from screening per 100,000 compared with no comorbidities, and our results can be used by clinicians when discussing the benefits and harms of screening in their patients with comorbidities.

Abstract Background Immune checkpoint inhibitors targeting the programmed cell death protein‐1 (PD‐1) and programmed death ligand‐1 (PD‐L1) axis (collectively referred to as PD[L]1i) have demonstrated clinical benefits in non‐small cell lung cancer (NSCLC) patients. The purpose of this United States‐based real‐world study is to examine changes in the landscape of first‐line therapies for NSCLC since the introduction of PD(L)1i. Methods Patients with NSCLC initiating first‐line treatment between May 1, 2017, and October 31, 2020, were identified in the IBM MarketScan® database. Patients were assigned groups based on first‐line therapy: PD(L)1i monotherapy, chemotherapy alone, PD(L)1i with chemotherapy, or targeted therapy for patients with actionable driver mutations. Results A total of 5431 patients with NSCLC starting first‐line treatment were identified: chemotherapy alone 2568 (47%), PD(L)1i with chemotherapy 1364 (25%), PD(L)1i monotherapy 790 (15%), and targeted therapy 709 (13%). The use of PD(L)1i monotherapy and targeted therapy remained consistent, while the percentage of patients receiving PD(L)1i with chemotherapy more than doubled. Over a third of patients in 2019 and 2020 received chemotherapy alone. Patients aged ≥65 years (odds ratio [OR]: 0.80; 95% confidence interval [CI]: 0.68–0.95), females (OR: 0.86; 95% CI: 0.74–0.98), and those with respiratory (OR: 0.82; 95% CI: 0.71–0.94) or kidney (OR: 0.56; 95% CI: 0.40–0.77) disease were less likely to have received PD(L)1i with chemotherapy than patients that received chemotherapy alone. Conclusions Since the approval of PD(L)1i for NSCLC, their use has significantly increased for first‐line treatment, especially when used in combination with chemotherapy. A significant proportion of patients received chemotherapy alone.

Summary: Background: In this study, we compare management of patients with high-risk chronic obstructive pulmonary disease (COPD) in the United States to national and international guidelines and quality standards, including the COllaboratioN on QUality improvement initiative for achieving Excellence in STandards of COPD care (CONQUEST). Methods: Patients were identified from the DARTNet Practice Performance Registry and categorized into three high-risk cohorts in each year from 2011 to 2019: newly diagnosed (≤12 months after diagnosis), already diagnosed, and patients with potential undiagnosed COPD. Patients were considered high-risk if they had a history of exacerbations or likely exacerbations (respiratory consult with prescribed medication). Descriptive statistics for 2019 are reported, along with annual trends. Findings: In 2019, 10% (n = 16,610/167,197) of patients met high-risk criteria. Evidence of spirometry for diagnosis was low; in 2019, 81% (n = 1228/1523) of patients newly diagnosed at high-risk had no record of spirometry/peak expiratory flow in the 12 months pre- or post-diagnosis and 43% (n = 651/1523) had no record of COPD symptom review. Among those newly and already diagnosed at high-risk, 52% (n = 4830/9350) had no evidence of COPD medication. Interpretation: Findings suggest inconsistent adherence to evidence-based guidelines, and opportunities to improve identification, documentation of services, assessment, therapeutic intervention, and follow-up of patients with COPD. Funding: This study was conducted by the Observational and Pragmatic Research Institute (OPRI) Pte Ltd and was partially funded by Optimum Patient Care Global and AstraZeneca Ltd. No funding was received by the Observational & Pragmatic Research Institute Pte Ltd (OPRI) for its contribution.

Abstract Background Medical centers with varying levels of expertise treat gastroenteropancreatic neuroendocrine tumors (GEP-NETs), which are relatively rare tumors. This study assesses the impact of center volume on GEP-NET treatment outcomes. Methods We used the Surveillance, Epidemiology, and End Results (SEER) registry linked to Medicare claims data. The data includes patients diagnosed between 1995 and 2010 who had no health maintenance organization (HMO) coverage, participated in Medicare parts A and B, were older than 65 at diagnosis, had tumor differentiation information, and had no secondary cancer. We identified medical centers at which patients received GEP-NET treatment (surgery, chemotherapy, somatostatin analogues, or radiation therapy) using Medicare claims data. Center volume was divided into 3 tiers – low, medium, and high – based on the number of unique GEP-NET patients treated by a medical center over 2 years. We used Kaplan-Meier curves and Cox regression to assess the association between volume and disease-specific survival. Results We identified 899 GEP-NET patients, of whom 37, 45, and 18% received treatment at low, medium volume, and high-volume centers, respectively. Median disease-specific survival for patients at low and medium tiers were 1.4 years and 5.3 years, respectively, but was not reached for patients at high volume centers. Results showed that patients treated at high volume centers had better survival than those treated in low volume centers (HR: 0.63, 95% CI: 0.4–0.9), but showed no difference in outcomes between medium and high-volume centers. Conclusions Our results suggest that for these increasingly common tumors, referral to a tertiary care center may be indicated. Physicians caring for GEP-NET patients should consider early referral to high volume centers.

Abstract Objective Although the prognostic role of human papilloma virus (HPV) status in oropharyngeal head and neck squamous cell carcinoma (SCC) is well established, growing evidence shows that there may be a prognostic role for HPV status in hypopharyngeal SCC. The objective of this study was to determine the prognostic role of HPV status in hypopharyngeal SCC. Methods We performed a retrospective, population‐based analysis of 1934 adult patients with HNSCC diagnosed between 2010‐2016 and treated with a combination of surgery and/or radiotherapy, with or without chemotherapy, and a subset of 641 patients with hypopharyngeal SCC and known HPV status included in the Surveillance, Epidemiology, and End Results (SEER) Head and Neck with HPV Status Database. Patient data were used to determine the adjusted 2‐year cancer‐specific survival (CSS) and overall survival (OS) for the entire cohort and the specific subgroup of hypopharyngeal cancer patients with known HPV status. Results Of the 1934 hypopharynx SCC cases, HPV status was unknown in 1294 (66.9%), and 167 (8.6%) were HPV positive; among hypopharynx cases with known HPV status, 21.6% were HPV positive. In models adjusting for sex, age, race/ethnicity, marital status and stage, patients with HPV‐positive hypopharyngeal tumors had improved CSS compared with patients with HPV‐negative tumors (CSS: HR: .57, 95% CI = .38 to .86, P = .008; OS: HR: .49, 95% CI = .34 to .71, P =

BackgroundVeterans are at increased risk of lung cancer and many have comorbidities such as chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD). We used simulation modeling to assess projected outcomes associated with different management strategies of Veterans with stage I non-small cell lung cancer (NSCLC) with COPD and/or CAD.Patients and methodsUsing data from a cohort of 14,029 Veterans (years 2000-2015) with NSCLC we extended a well-validated mathematical model of lung cancer to represent the management and outcomes of Veterans with stage I NSCLC with COPD, with or without comorbid CAD. We simulated multiple randomized trials to compare treatment with lobectomy, limited resection, or stereotactic body radiation therapy (SBRT). Model output estimated expected quality adjusted life years (QALY) of Veterans with stage I NSCLC according to age, tumor size, histologic subtype, COPD severity and CAD diagnosis.ResultsFor Veterans ConclusionsThe harm/benefit ratio of treatments for stage I NSCLC among Veterans may vary according to COPD severity and the presence of CAD. This information can be used to direct future research study design for Veterans with stage I lung cancer and COPD and/or CAD.

ObjectivesWhile previous cost-effectiveness studies on pembrolizumab in stage IV non-small cell lung cancer (NSCLC) have found these regimens to be cost-effective, their reliance on randomized controlled trial (RCT) data with strict inclusion criteria limits generalizability to patients with comorbidities. We estimated the cost-effectiveness of first-line pembrolizumab for patients with various comorbidities.Materials and methodsIn our base case analysis, we studied pembrolizumab plus chemotherapy (pembrolizumab combination therapy) versus chemotherapy alone. In a secondary analysis, we considered only patients with PD-L1 expression of at least 50% (PD-L1-high) and evaluated pembrolizumab monotherapy, pembrolizumab combination therapy, and chemotherapy alone. Microsimulation models were developed for the base case and the PD-L1-high analyses. To estimate outcomes of patients with differing comorbidities, we combined survival data from patients with few or no comorbidities from the RCTs with estimates from the general population obtained from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Comorbidity burden level was divided into three groups based on the Charlson score (equal to 0, 1, or 2+); patients with various other specific comorbidities were also analyzed. Incremental cost-effectiveness ratios (ICER) were compared to a willingness-to-pay (WTP) threshold of $100,000/quality-adjusted life-year (QALY).ResultsIn the Charlson 0, Charlson 1, and Charlson 2+ patient populations, estimated ICERs for pembrolizumab combination therapy in the base case model were $173,919/QALY, $175,165/QALY, and $181,777/QALY, respectively, compared to chemotherapy. In the PD-L1-high model, the Charlson 0, Charlson 1, and Charlson 2+ patients had ICERs of $147,406/QALY, $149,026/QALY, and $154,521/QALY with pembrolizumab combination therapy versus chemotherapy. Pembrolizumab monotherapy was weakly dominated for each comorbidity group in the PD-L1-high model.ConclusionFor patients with stage IV NSCLC and varying comorbidity burden, first-line treatment with pembrolizumab does not represent a cost-effective strategy compared to chemotherapy. Resources should be focused on collecting immunotherapy survival data for more representative NSCLC patient populations.

Objectives Disadvantaged older adults may benefit from social support in adhering to their medications, but the multidimensional nature of social relationships makes it difficult to identify the most relevant domain. We examined associations of structural and functional support with medication adherence among a cohort of older adults with asthma.Design Cross-sectional analysis of the Asthma Beliefs and Literacy in the Elderly cohort study.Setting Outpatient clinics in New York, New York, and Chicago, Illinois, USA.Participants English-speaking and Spanish-speaking older adults (≥60 years) with asthma.Outcome measures Medication adherence was measured using dose counts from inhaler and self-report.Results Among 383 participants, the mean age was 67 years, 38% identified as Hispanic, 33% identified as black, 52% reported monthly incomes ≤US$1350 and 64% demonstrated poor adherence to their asthma controller medication. Structural and functional support were weakly correlated (r=−0.15, p=0.005). In adjusted analyses, structural support was not associated with medication adherence. Participants who received infrequent functional support in managing their medications had lower odds of poor adherence according to dose counts (OR 0.51, 95% CI 0.26 to 0.98), but not when assessed via self-report (OR 0.81, 95% CI 0.44 to 1.48).Conclusion The receipt of frequent functional support in managing medications was associated with poor adherence to asthma controller medications. Further research is needed to better understand the manner and context which functional support operates in relation to medication adherence among older adults.

Diseases of the respiratory system are a leading cause of morbidity, mortality and disability worldwide. The lungs are constantly exposed to a myriad of noxious agents present in ambient air, such as particles, chemicals and infectious organisms. At least 2 billion people are exposed globally to the toxic smoke produced by combustion of biomass fuel, inefficiently burned in poorly ventilated indoor stoves or fireplaces used for cooking or warming. One billion people inhale polluted outdoor air, and another billion are exposed primarily or secondarily to tobacco smoke. As a consequence, respiratory disease is a major cause of morbidity, disability and death worldwide primarily affecting individuals of low socioeconomic status, who are exposed to crowding, environmental exposures and poor living conditions.

Purpose: Reporting adverse events is a critical element of a clinical trial publication. In 2003, the Consolidated Standards of Reporting Trials (CONSORT) group generated recommendations regarding the appropriate reporting of adverse events. The degree to which these recommendations are followed in oncology publications has not been comprehensively evaluated., Methods: A review of citations from PubMed, Medline, and Embase published between Jan 1, 2009 and December 31, 2011, identified eligible randomized, controlled phase III trials in metastatic solid malignancies. Publications were assessed for 14 adverse event-reporting elements derived from the CONSORT harms extension statement; a completeness score (range, 0 to 14) was calculated by adding the number of elements reported. Linear regression analysis identified which publication characteristics associated with reporting completeness., Results: A total of 175 publications, with data for 96,125 patients, were included in the analysis. The median completeness score was eight (range, three to 12). Most publications (96%) reported only adverse events occurring above a threshold rate or severity, 37% did not specify the criteria used to select which adverse events were reported, and 88% grouped together adverse events of varying severity. Regression analysis revealed that trials without a stated funding source and with an earlier year of publication had significantly lower completeness scores., Conclusion: Reporting of adverse events in oncology publications of randomized trials is suboptimal and characterized by substantial selectivity and heterogeneity. The development of oncology-specific standards for adverse event reporting should be established to ensure consistency and provide critical information required for medical decision-making.