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Context: Lung cancer is the leading cause of cancer death. Most patients are diagnosed with advanced disease, resulting in a very low 5-year survival. Screening may reduce the risk of death from lung cancer.Objective: To conduct a systematic review of the evidence regarding the benefits and harms of lung cancer screening using low-dose computed tomography (LDCT). A multisociety collaborative initiative (involving the American Cancer Society, American College of Chest Physicians, American Society of Clinical Oncology, and National Comprehensive Cancer Network) was undertaken to create the foundation for development of an evidence-based clinical guideline.Data Sources: MEDLINE (Ovid: January 1996 to April 2012), EMBASE (Ovid: January 1996 to April 2012), and the Cochrane Library (April 2012).Study Selection: Of 591 citations identified and reviewed, 8 randomized trials and 13 cohort studies of LDCT screening met criteria for inclusion. Primary outcomes were lung cancer mortality and all-cause mortality, and secondary outcomes included nodule detection, invasive procedures, follow-up tests, and smoking cessation.Data Extraction: Critical appraisal using predefined criteria was conducted on individual studies and the overall body of evidence. Differences in data extracted by reviewers were adjudicated by consensus.Results: Three randomized studies provided evidence on the effect of LDCT screening on lung cancer mortality, of which the National Lung Screening Trial was the most informative, demonstrating that among 53,454 participants enrolled, screening resulted in significantly fewer lung cancer deaths (356 vs 443 deaths; lung cancer−specific mortality, 274 vs 309 events per 100,000 person-years for LDCT and control groups, respectively; relative risk, 0.80; 95% CI, 0.73-0.93; absolute risk reduction, 0.33%; P = .004). The other 2 smaller studies showed no such benefit. In terms of potential harms of LDCT screening, across all trials and cohorts, approximately 20% of individuals in each round of screening had positive results requiring some degree of follow-up, while approximately 1% had lung cancer. There was marked heterogeneity in this finding and in the frequency of follow-up investigations, biopsies, and percentage of surgical procedures performed in patients with benign lesions. Major complications in those with benign conditions were rare.Conclusion: Low-dose computed tomography screening may benefit individuals at an increased risk for lung cancer, but uncertainty exists about the potential harms of screening and the generalizability of results. [ABSTRACT FROM AUTHOR]

Background: This study was undertaken to characterize the relation between the survival of patients with stage IIIB/IV nonsmall cell lung cancer (NSCLC) and pack-years of cigarette smoking (graded according to the American Joint Committee on Cancer staging system).Methods: Data were analyzed from patients with stage IIIB/IV NSCLC who had completed a prospective smoking questionnaire. The impact of pack-years of cigarette smoking, age, sex, Karnofsky performance status (KPS), and the presence of weight loss >5% was evaluated on overall survival using univariate and multivariate analyses.Results: Smoking history and clinical data were available for 2010 patients with stage IIIB/IV NSCLC (1004 women and 1006 men). Approximately 70% of patients (1409 patients) had smoked >15 pack-years, 13% (270) were former and current smokers who had smoked < or = 15 pack-years, and 16% (331) were never-smokers (<100 lifetime cigarettes). Never-smokers had a longer median survival compared with former or current smokers (17.8 months vs 11.3 months; log-rank P < .001). Among smokers, patients with a < or = 15 pack-year history of smoking had a longer median survival than patients who had smoked >15 pack-years (14.6 months vs 10.8 months; log-rank P = .03). As the number of pack-years increased, the median overall survival decreased (log-rank P < .001). Multivariate analysis indicated that a history of smoking was an independent prognostic factor (hazard ratio, 1.36; P < .001).Conclusions: More cigarette smoking, measured in pack-years, was associated with decreased survival after a diagnosis of stage IIIB/IV NSCLC. Trials assessing survival in patients with stage IIIB/IV NSCLC should report a detailed cigarette smoking history for all patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Fragmentation across sites of care may impede efficient healthcare delivery. OBJECTIVES: The objectives of this study were to evaluate fragmentation of hospital care for chronically ill New York City (NYC) residents and its association with enrollment in the New York State (NYS) Medicaid program. RESEARCH DESIGN: We conducted a cross-sectional study using the NYS Department of Health's Statewide Planning and Research Cooperative System discharge database. We identified 53,031 NYC residents admitted 3 or more times to acute care hospitals between 2000 and 2002 with the same principal diagnosis of a specific chronic illness (diabetes, sickle cell anemia, psychosis, substance abuse, cancer, gastrointestinal disease, chronic obstructive pulmonary disease/asthma, coronary artery disease, or congestive heart failure). We also evaluated a larger cohort of 225,421 patients with >or=3 admissions for a specific chronic illness coded as either the principal or a secondary diagnosis. A generalized logit model was used to examine the relationship between fragmentation and each patient's primary insurance adjusted for diagnosis and demographic characteristics. MEASURES: Fragmentation was characterized as high, moderate, or low based on the number of distinct hospitals a patient visited relative to the patient's total number of hospitalizations over the 3-year interval. RESULTS: Among frequently hospitalized NYC residents with select chronic conditions, 17.1% experienced highly fragmented care. This rate was 9.9% for patients with commercial insurance, 24.4% for those with Medicaid, and 9.7% for those with Medicare. The unadjusted odds ratio describing high fragmentation of Medicaid enrollees compared with commercially insured patients was 3.82 (95% confidence interval [CI], 3.50-4.18) and, although attenuated, remained significant after adjustment for demographic characteristics (odds ratio, 1.33; 95% CI, 1.20-1.47). The strongest predictor of fragmentation was a diagnosis of psychosis (OR, 2.81; 95% CI, 2.43-3.25) or substance abuse (OR, 7.58; 95% CI, 6.55-8.77). CONCLUSIONS: In NYC, Medicaid enrollment is associated with greater fragmentation of hospital care, but this is largely attributable to the preponderance of Medicaid enrollees with diagnoses of psychosis and substance abuse. Strategies to improve the efficiency of healthcare delivery should focus on patients with mental illness who are frequently admitted to general hospitals. [ABSTRACT FROM AUTHOR]

Study Objectives: Investigators have been using severity-of-illness indexes such as APACHE II (acute physiology and chronic health evaluation score II) to describe patients with prolonged critical illness. However, little is known about the utility of these indexes for this patient population. We evaluated the ability of four severity-of-illness indexes to predict mortality rates in 182 patients with prolonged critical illness.Design: Retrospective inception cohort study.Setting: A single, urban, long-term, acute-care hospital in Chicago.Patients: One hundred eighty-two patients transferred from 37 acute-care hospital ICUs.Measurements and Results: We assessed four indexes: the acute physiology and chronic health evaluation II, the simplified acute physiology score II, the mortality prediction model II, and the logistic organ dysfunction system using variables measured on admission to the long-term acute-care hospital ICU. We found that none of these indexes distinguished well between the patients who lived and the patients who died (area under ROC [receiver operating characteristics] curve < 0.70 for all), nor did they assign correct probabilities of death to individual patients (Hosmer-Lemeshow goodness-of-fit statistics, p < 0.01 for all).Conclusions: Investigators and clinicians should use caution in using severity-of-illness measures developed for acutely ill patients to describe critically ill patients admitted to long-term care units. As clinical practice and research focus more on these latter patients, development of adequately performing severity-of-illness measures appropriate to this patient population will be needed. [ABSTRACT FROM AUTHOR]

Study Objectives: To critically review the available data on the diagnostic evaluation, risk stratification, and therapeutic management of patients with acute exacerbations of COPD.Design, Setting, and Participants: English-language articles were identified from the following databases: MEDLINE (from 1966 to week 5, 2000), EMBASE (from 1974 to week 18, 2000), HealthStar (from 1975 to June 2000), and the Cochrane Controlled Trials Register (2000, issue 1). The best available evidence on each subtopic then was selected for analysis. Randomized trials, sometimes buttressed by cohort studies, were used to evaluate therapeutic interventions. Cohort studies were used to evaluate diagnostic tests and risk stratification. Study design and results were summarized in evidence tables. Individual studies were rated as to their internal validity, external validity, and quality of study design. Statistical analyses of combined data were not performed.Measurement and Results: Limited data exist regarding the utility of most diagnostic tests. However, chest radiography and arterial blood gas sampling appear to be useful, while short-term spirometry measurements do not. In terms of the risk of relapse and the risk of death after hospitalization for an acute exacerbation, there are identifiable clinical variables that are associated with these outcomes. Therapies for which there is evidence of efficacy include bronchodilators, corticosteroids, and noninvasive positive-pressure ventilation. There is also support for the use of antibiotics in patients with more severe exacerbations. Based on limited data, mucolytics and chest physiotherapy do not appear to be of benefit, and oxygen supplementation appears to increase the risk of respiratory failure in an identifiable subgroup of patients.Conclusions: Although suggestions for appropriate management can be made based on available evidence, the supporting literature is spotty. Further high-quality research is needed and will require an improved, generally acceptable, and transportable definition of the syndrome "acute exacerbation of COPD" and improved methods for observing and measuring outcomes. [ABSTRACT FROM AUTHOR]

Background: Lung cancer typically exhibits symptoms only after the disease has spread, making cure unlikely. Because early-stage disease can be successfully treated, a screening technique that can detect lung cancer before it has spread might be useful in decreasing lung cancer mortality. Objectives: In this article, we review the evidence for and against screening for lung cancer with low-dose CT and offer recommendations regarding its usefulness for asymptomatic patients with no history of cancer. Results: Studies of lung cancer screening with chest radiograph and sputum cytology have failed to demonstrate that screening lowers lung cancer mortality rates. Published studies of newer screening technologies such as low-dose CT and "biomarker" screening report primarily on lung cancer detection rates and do not present sufficient data to determine whether the newer technologies will benefit or harm. Although researchers are conducting randomized trials of low-dose CT, results will not be available for several years. In the meantime, cost-effectiveness analyses and studies of nodule growth are considering practical questions but producing inconsistent findings. Conclusions: For high-risk populations, no screening modality has been shown to alter mortality outcomes. We recommend that individuals undergo screening only when it is administered as a component of a well-designed clinical trial with appropriate human subjects' protections. [ABSTRACT FROM AUTHOR]

Although virtually all individuals with advanced lung cancer succumb to the disease, a substantial portion of individuals diagnosed at an earlier stage can be cured. This dichotomy has provoked interest in lung cancer screening. To date, randomized controlled trials of chest x-ray and sputum cytology have failed to demonstrate that screening with either modality decreases lung cancer mortality; neither of these technologies can be recommended. Early studies of lung cancer screening with low-dose CT (LDCT) appear promising; however, only data from observational studies are available. We recommend that individuals should only be screened with LDCT in the context of well-designed clinical trials. [ABSTRACT FROM AUTHOR]

Study Objectives: To review the available data on the early detection of lung cancer, with a focus on three technologies: chest x-ray (CXR), sputum cytology, and low-dose CT (LDCT) scanning.Design, Setting, Participants: Review of published clinical studies of early detection technologies. The best available evidence on each topic was selected for analysis. Randomized trials were used to evaluate CXR and sputum cytology. Cohort studies, as well as studies providing evidence regarding rates of overdiagnosis and efficacy of initial treatment, were considered in evaluation of LDCT. Study design and results were summarized in evidence tables. Statistical analyses of combined data were not performed.Measurement and Results: Five randomized trials of CXR with or without sputum cytology have been conducted, each which reports disease-specific mortality as well as other end points. None of these studies provide support for the use of either CXR or sputum cytology for the early detection of lung cancer in asymptomatic individuals. Eight completed and ongoing trials of LDCT were identified. All of these studies report the frequency and stage distribution of lung cancers found during initial ("prevalence") screening, and several studies also report rates of detection at the time of annual follow-up. No outcome data on survival or treatment are available. A number of studies support the hypothesis of "overdiagnosis"--that some lung cancers detected by LDCT may behave in an indolent manner.Conclusions: The use of either CXR or sputum cytology for the early detection of lung cancer is not supported by the published evidence. The evidence for LDCT appears promising, in that the technology typically identifies lung cancer at an early stage, although corollary studies suggest that these findings in isolation may be misleading. Further high-quality research is needed to better define the role of LDCT in the evaluation of asymptomatic high-risk individuals. [ABSTRACT FROM AUTHOR]

Background: Despite controversy surrounding the use of funds arising from settlement agreements with the tobacco industry, little is known about the role of these funds in expenditures for state tobacco-control programs.Methods: We evaluated state expenditures for tobacco-control programs in fiscal year 2001 in the context of the amount of tobacco-settlement funds received and allocated to tobacco-control programs and in the context of other state-level economic and health data.Results: In 2001 the average state received $28.35 per capita from the tobacco settlement but allocated approximately 6 percent of these funds to tobacco-control programs. The average state dedicated $3.49 per capita (range, $0.10 to $15.47) to tobacco-control programs. The proportion of settlement funds allocated to tobacco-control programs varied from 0 to 100 percent and was strongly related to levels of tobacco-control funding (P<0.001). States with higher smoking rates tended to invest less per capita in tobacco-control programs (P=0.007), as did tobacco-producing states (the mean per capita expenditure was $1.20, as compared with $3.81 in non-tobacco-producing states; P<0.008). In a multivariate analysis, the proportion of the settlement revenue allocated to tobacco-control programs was the primary determinant of the level of total funding; the state tobacco-related health burden was unrelated to program funding.Conclusions: State health needs appear to have little effect on the funding of state tobacco-control programs. Because only a very small proportion of the tobacco settlement is being used for tobacco-control programs, the settlement represents an unrealized opportunity to reduce morbidity and mortality from smoking. [ABSTRACT FROM AUTHOR]

Lung cancer screening via annual low-dose computed tomography has poor adoption. We conducted a prospective case-control study among 958 individuals eligible for lung cancer screening to develop a blood-based lung cancer detection test that when positive is followed by a low-dose computed tomography. Changes in genome-wide cell-free DNA fragmentation profiles (fragmentomes) in peripheral blood reflected genomic and chromatin characteristics of lung cancer. We applied machine learning to fragmentome features to identify individuals who were more or less likely to have lung cancer. We trained the classifier using 576 cases and controls from study samples and validated it in a held-out group of 382 cases and controls. The validation demonstrated high sensitivity for lung cancer and consistency across demographic groups and comorbid conditions. Applying test performance to the screening eligible population in a 5-year model with modest utilization assumptions suggested the potential to prevent thousands of lung cancer deaths. Significance: Lung cancer screening has poor adoption. Our study describes the development and validation of a novel blood-based lung cancer screening test utilizing a highly affordable, low-coverage genome-wide sequencing platform to analyze cell-free DNA fragmentation patterns. The test could improve lung cancer screening rates leading to substantial public health benefits. See related commentary by Haber and Skates, p. 2025., (©2024 The Authors; Published by the American Association for Cancer Research.)

Circulating cell-free DNA (cfDNA) assays for monitoring individuals with cancer typically rely on prior identification of tumor-specific mutations. Here, we develop a tumor-independent and mutation-independent approach (DELFI-tumor fraction, DELFI-TF) using low-coverage whole genome sequencing to determine the cfDNA tumor fraction and validate the method in two independent cohorts of patients with colorectal or lung cancer. DELFI-TF scores strongly correlate with circulating tumor DNA levels (ctDNA) (r = 0.90, p < 0.0001, Pearson correlation) even in cases where mutations are undetectable. DELFI-TF scores prior to therapy initiation are associated with clinical response and are independent predictors of overall survival (HR = 9.84, 95% CI = 1.72-56.10, p < 0.0001). Patients with lower DELFI-TF scores during treatment have longer overall survival (62.8 vs 29.1 months, HR = 3.12, 95% CI 1.62-6.00, p < 0.001) and the approach predicts clinical outcomes more accurately than imaging. These results demonstrate the potential of using cfDNA fragmentomes to estimate tumor burden in cfDNA for treatment response monitoring and clinical outcome prediction., (© 2024. The Author(s).)

Purpose: The Medicare part D Low-Income Subsidy (LIS) improves access to oral cancer drugs, but provides no assistance for clinician-administered/part B drugs. This analysis assessed the association between LIS participation and receipt of optimal cancer treatment., Methods: We investigated initial systemic therapy using SEER-Medicare data (2015-2017) and National Comprehensive Cancer Network (NCCN) Evidence Blocks (EB) as the standard for treatment recommendations. We included cancer clinical scenarios wherein (1) ≥one treatment was optimal (higher efficacy and safety scores) versus other treatments; (2) identifiable in SEER-Medicare (eg, not defined by clinical data unavailable in registry data or claims); and (3) both EB and ASCO Value Framework agreed regarding optimal treatment. We fit logistic regression models to assess the association between receipt of systemic therapy ( v no therapy) and patient and provider characteristics. Contingent on receipt of treatment, we modeled the likelihood of receiving a treatment ranked (by EB scores) within the highest or lowest quartile for that cancer type., Results: Nine thousand two hundred and ninety patients were included across 11 clinical scenarios. Fifty-seven percent (5,336) of patients received any systemic therapy and 43% (3,954) received no systemic therapy. Compared with non-LIS participants, LIS participants were less likely to receive any systemic therapy versus no systemic therapy (odds ratio, 0.64 [95% CI, 0.57 to 0.72]). Contingent on receiving systemic therapy, LIS participants received treatment ranked within the worst quartile 24.8% of the time, compared with 21.9% of non-LIS patients (adjusted prevalence difference, 4.3% [95% CI, 0.5 to 8.2])., Conclusion: LIS participants were less likely to receive systemic therapy at all and were more likely to receive treatments that receive low NCCN EB scores.

Lung cancer mortality rates, particularly non-small cell lung cancer (NSCLC), continue to present a significant global health challenge, and the adoption of lung cancer screening remains limited, often influenced by inequities in access to healthcare. Despite clinical evidence demonstrating the efficacy of annual screening with low-dose computed tomography (LDCT) and recommendations from medical organizations including the U.S. Preventive Services Task Force (USPSTF), the national lung cancer screening uptake remains around 5% among eligible individuals. Advancements in the clinical management of NSCLC have recently become more personalized with the implementation of blood-based biomarker testing. Extensive research into tumor-derived cell-free DNA (cfDNA) through fragmentation offers a novel method for improving early lung cancer detection. This review assesses the screening landscape, explores obstacles to lung cancer screening, and discusses how a plasma whole genome fragmentome test (pWGFrag-Lung) can improve lung cancer screening participation and adherence.

Background: Industry payments to US cancer centers are poorly understood., Methods: US National Cancer Institute (NCI)-designated comprehensive cancer centers were identified (n = 51). Industry payments to NCI-designated comprehensive cancer centers from 2014 to 2021 were obtained from Open Payments and National Institutes of Health (NIH) grant funding from NIH Research Portfolio Online Reporting Tools (RePORT). Given our focus on cancer centers, we measured the subset of industry payments related to cancer drugs specifically and the subset of NIH funding from the NCI., Results: Despite a pandemic-related decline in 2020-2021, cancer-related industry payments to NCI-designated comprehensive cancer centers increased from $482 million in 2014 to $972 million in 2021. Over the same period, NCI research grant funding increased from $2 481  million to $2 724  million. The large majority of nonresearch payments were royalties and licensing payments., Conclusion: Industry payments to NCI-designated comprehensive cancer centers increased substantially more than NCI funding in recent years but were also more variable. These trends raise concerns regarding the influence and instability of industry payments., (© The Author(s) 2024. Published by Oxford University Press.)

Objective: To estimate the association between oncologists' receipt of payments from the pharmaceutical industry and delivery of non-recommended or low value interventions among their patients., Design: Cohort study., Setting: Fee-for-service Medicare claims., Participants: Medicare beneficiaries with a diagnosis of incident cancer (new occurrence of a cancer diagnosis code in proximity to claims for cancer treatment, and no such diagnosis codes during a ≥1 year washout period) during 2014-19, who met additional requirements identifying them as at risk for one of four non-recommended or low value interventions: denosumab for castration sensitive prostate cancer, granulocyte colony stimulating factors (GCSF) for patients at low risk for neutropenic fever, nab-paclitaxel for cancers with no evidence of superiority over paclitaxel, and a branded drug in settings where a generic or biosimilar version was available., Main Outcome Measures: Receipt of the non-recommended or low value drug for which the patient was at risk. The primary association of interest was the assigned oncologist's receipt of any general payments from the manufacturer of the corresponding non-recommended or low value drug (measured in Open Payments) within 365 days before the patient's index cancer date. The two modeling approaches used were general linear model controlling for patients' characteristics and calendar year, and general linear model with physician level indicator variables., Results: Oncologists were in receipt of industry payments for 2962 of 9799 patients (30.2%) at risk for non-recommended denosumab (median $63), 76 747 of 271 485 patients (28.3%) at risk for GCSF (median $60); 18 491 of 86 394 patients (21.4%) at risk for nab-paclitaxel (median $89), and 4170 of 13 386 patients (31.2%) at risk for branded drugs (median $156). The unadjusted proportion of patients who received non-recommended denosumab was 31.4% for those whose oncologist had not received payment and 49.5% for those whose oncologist had (prevalence difference 18.0%); the corresponding values for GCSF were 26.6% v 32.1% (5.5%), for nab-paclitaxel were 7.3% v 15.1% (7.8%), and for branded drugs were 88.3% v 83.5% (-4.8%). Controlling for patients' characteristics and calendar year, payments from industry were associated with increased use of denosumab (17.5% (95% confidence interval 15.3% to 19.7%)), GCSF (5.8% (5.4% to 6.1%)), and nab-paclitaxel (7.6% (7.1% to 8.1%)), but lower use of branded drugs (-4.6% (-5.8% to -3.3%)). In physician level indicator models, payments from industry were associated with increased use of denosumab (7.4% (2.5% to 12.2%)) and nab-paclitaxel (1.7% (0.9% to 2.5%)), but not with GCSF (0.4% (-0.3% to 1.1%)) or branded drugs (1.2% (-6.0 to 8.5%))., Conclusions: Within some clinical scenarios, industry payments to physicians are associated with non-recommended and low value drugs. These findings raise quality of care concerns about the financial relationships between physicians and industry., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the National Cancer Institute and Institute of Health Care management; no support from any organization for the submitted work for the submitted work. AMM declares stock ownership in DNA and Teladoc Health. NT declares employment and stock options at Delfi Diagnostics. PB declares consulting/advisory role at EQRx, leadership roles at Delfi Diagnostics and Oncology Analytics, travel expenses paid by Oncology Analytics, stock ownership at EQRx, Oncology Analytics, and Delfi Diagnostics, and research funding by Kaiser Permanente and Arnold Ventures. ANW declares consulting with Takeda and CorMedix., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The diagnostic workup of individuals suspected of having lung cancer can be complex and protracted because conventional symptoms of lung cancer have low specificity and sensitivity., Research Question: Among individuals with symptoms of lung cancer, can a blood-based approach to analyze cell-free DNA (cfDNA) fragmentation (the DNA evaluation of fragments for early interception [DELFI] score) enhance evaluation for the possible presence of lung cancer?, Study Design and Methods: Adults were referred to Bispebjerg Hospital (Copenhagen, Denmark) for diagnostic evaluation of initial imaging anomalies and symptoms consistent with lung cancer. Numbers and types of symptoms were extracted from medical records. cfDNA from plasma samples obtained at the prediagnostic visit was isolated, sequenced, and analyzed for genome-wide cfDNA fragmentation patterns. The relationships among clinical presentation, cancer status, and DELFI score were examined., Results: A total of 296 individuals were analyzed. Median DELFI scores were higher for those with lung cancer (n = 98) than those without cancer (n = 198; 0.94 vs 0.19; P < .001). In a multivariate model adjusted for age, smoking history, and presenting symptoms, the addition of the DELFI score improved the prediction of lung cancer for those who demonstrated symptoms (area under the receiver operating characteristic curve, 0.74-0.94)., Interpretation: The DELFI score distinguishes individuals with lung cancer from those without cancer better than suspicious symptoms do. These results represent proof-of-concept support that fragmentation-based biomarker approaches may facilitate diagnostic resolution for patients with concerning symptoms of lung cancer., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Rapid advancements in the area of early cancer detection have brought us closer to achieving the goals of finding cancer early enough to treat or cure it, while avoiding harms of overdiagnosis. We evaluate progress in the development of early cancer detection tests in the context of the current principles for cancer screening. We review cell-free DNA (cfDNA)-based approaches using mutations, methylation, or fragmentomes for early cancer detection. Lastly, we discuss the challenges in demonstrating clinical utility of these tests before integration into routine clinical care., Competing Interests: Competing interests: The authors declare the following competing interests: NCD, PBB, and AL report that they are employees of and have stock ownership in Delfi Diagnostics. RBS reports grants and personal fees from Delfi Diagnostics outside the submitted work; a patent for US-2022-0325343 licensed to Delfi Diagnostics; and is a founder of and holds equity in Delfi Diagnostics, and serves as the head of Data Science. This arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict-of-interest policies. GAM reports that his institution has received grants from SU2C-Dutch Cancer Society (KWF), Sysmex in-kind matching to KWF grant, MLDS and Health~Holland with in-kind matching from Exact Sciences, ZonMW with in-kind matching from HMF and Personal Genome Diagnostics (PGDx) and cash matching from CZ Health Insurance paid to the institution. GAM is named as a co-inventor on a patent issued for protein biomarkers for detection of colorectal cancer and patents pending related to biomarkers for colorectal cancer early detection and related cell-free DNA analyses. GAM is a participant in the Amgen Real-World Data group, for which he receives no compensation. GAM is a Board member and CSO of Health-RI, a Supervisory Board member of IKNL, a Co-national Node Leader of BBMRI-NL, and a National Node Director of EATRIS-NL. GAM is a co-founder, Board member, and CSO of CRCbioscreen BV. GAM reports research collaborations with Exact Sciences, Sysmex, Sentinel Ch. SpA, PGDx, Hartwig Medical Foundation, and Delfi Diagnostics, in which the companies have provided materials, equipment, and/or analyses. CLA reports that his institution has received grants or contracts from C2i Genomics, Delfi Diagnostics, and Natera. VEV is a founder of Delfi Diagnostics, serves on the Board of Directors and as an officer for this organization, and owns Delfi Diagnostics stock, which is subject to certain restrictions under university policy. Additionally, Johns Hopkins University owns equity in Delfi Diagnostics. VEV divested his equity in Personal Genome Diagnostics (PGDx) to LabCorp in February 2022. VEV is an inventor on patent applications submitted by Johns Hopkins University related to cancer genomic analyses and cell-free DNA for cancer detection that have been licensed to one or more entities, including Delfi Diagnostics, LabCorp, QIAGEN, Sysmex, Agios, Genzyme, Esoterix, Ventana and ManaT Bio. Under the terms of these license agreements, the University and inventors are entitled to fees and royalty distributions. VEV is an advisor to Viron Therapeutics and Epitope. These arrangements have been reviewed and approved by the Johns Hopkins University in accordance with its conflict-of-interest policies., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: About 10% of hospital inpatients are labelled with penicillin allergy in their electronic medical record (EMR). However, allergy is confirmed in less than 10% of these records. Consequently, 90% of patients are treated with broad-spectrum antibiotics, contributing to antimicrobial resistance. We aimed to explore experiences and practices of healthcare professionals that may explain incorrect labelling of penicillin allergy in Denmark and elucidate any consequences hereof., Methods: An electronic survey was distributed to physicians and nurses in six hospital units in Copenhagen and via social media. The survey was active from 19 March to 1 May 2020. Data were assessed using descriptive statistics and by thematic analysis., Results: The response rate was 44.6%. The survey had 369 participants; 152 physicians and 217 nurses. Half of the physicians and one in every five nurses had experienced problems treating patients with a penicillin allergy label. Physicians reported limited trust in allergy labels, and labelling practices varied. The risk that patients may be truly allergic was the main reason for not removing labels (72%), and a precautionary principle was identified related to penicillin allergy labelling., Conclusions: The penicillin allergy label is an independent factor of medication errors. Solutions to enhance patient safety may include education of physicians in allergy labelling, decision support, standardisation of the allergy registration in the various EMR systems used, and ideally also a national drug allergy register, which is accessible from all sectors., Funding: None., Trial Registration: Not relevant., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

In this investigation, cobalt ferrite nanoparticles (CFO NPs) were synthesized using a hydrothermal method. Then, silver nanoparticles (Ag NPs) were decorated on CFO NPs to form Ag/CFO NPs using jasmine extract as a reducing agent of Ag + ions. The properties of Ag/CFO NPs were characterized by X-ray powder diffraction, field-emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy, vibrating sample magnetometry, and catalytic tests in non-radiation conditions. The catalytic results indicated that the Ag/CFO NPs could activate peroxymonosulfate to generate sulfate radicals for the decomposition of different dyes such as methylene blue, methyl orange, and rhodamine B. For the Ag/CFO sample, Ag NPs validated the roles in dye adsorption, reduction of 4-nitrophenol, and improvement of antibacterial behavior. The growth inhibition activity of Ag/CFO NPs was observed against Pseudomonas aeruginosa (18.18 ± 2.48 mm) and Staphylococcus aureus (10.14 ± 0.72 mm). Furthermore, Ag/CFO NPs displayed good reusability after three consecutive runs. Therefore, Ag/CFO material is shown to be a potential multifunctional catalyst in wastewater treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Importance: Clinical trials play a critical role in the development of novel cancer therapies, and precise estimates of the frequency with which older adult patients with cancer participate in clinical trials are lacking., Objective: To estimate the proportion of older adult Medicare Fee-for-Service (FFS) beneficiaries with cancer who participate in interventional cancer clinical trials, using a novel population-based methodology., Design, Setting, and Participants: In this retrospective cohort study evaluating clinical trial participation among older adult patients with cancer from January 1, 2014, through June 30, 2020, claims data from Medicare FFS were linked with the ClinicalTrials.gov to determine trial participation through the unique National Clinical Trial (NCT) identifier. The proportion of patients with newly diagnosed or newly recurrent cancer in 2015 participating in an interventional clinical trial and receiving active cancer treatment from January 2014 to June 2020 was estimated. Data analysis was performed from November 18, 2020, to November 1, 2021., Exposures: Patients with cancer aged 65 years or older with Medicare FFS insurance, with and without active cancer treatment., Main Outcomes and Measures: Enrollment in clinical trials among all patients with cancer 65 years and older and among patients receiving active cancer treatments as defined by the presence of at least 1 NCT identifier corresponding to an interventional cancer clinical trial in Medicare claims., Results: Among 1 150 978 patients (mean [SD] age, 75.7 [8.4] years; 49.9% men and 50.1% women) with newly diagnosed or newly recurrent cancer in 2015, 12 028 (1.0%) patients had a billing claim with an NCT identifier indicating enrollment in an interventional cancer clinical trial between January 2014 and June 2020. In a subset of 429 343 patients with active cancer treatment, 8360 (1.9%) were enrolled in 1 or more interventional trials. Patients enrolled in a trial tended to be younger, male, a race other than Black, and residing in zip codes with high median incomes., Conclusions and Relevance: Findings of this cohort study show that clinical trial enrollment among older adult patients with cancer remains low, with only 1.0% to 1.9% of patients with newly diagnosed or recurrent cancer in 2015 participating in an interventional cancer clinical trial as measured by the presence of NCT identifiers in Medicare claims. These data provide a contemporary estimate of trial enrollment, persistent disparities in trial participation, and only limited progress in trial access over the past 2 decades.

Payments from the pharmaceutical industry to US physicians are common. In determining which payments rise to the level of an illegal kickback under the Anti-Kickback Statute (AKS), the Department of Health and Human Services' Office of Inspector General (OIG) has stated in nonbinding guidance that influencing or "swaying" physician prescribing is key. OIG has highlighted as a compliance standard the Pharmaceutical Research and Manufacturers of America Code on Interactions with Health Professions, which stipulates that permissible payments are those that do not interfere with prescribing. However, recent evidence has shown that most payments influence physician prescribing, driving higher prescription drug costs by increasing use of brand-name and low-value drugs. This evidence implies that many payments that are currently commonplace could be subject to prosecution under AKS. Given that these payments increase costs to patients and the health care system, there is a public interest in curtailing them. This article proposes a range of actions available to stakeholders-including industry, providers, regulators, and payers-to mitigate the cost-increasing effect of industry payments to physicians., (Copyright © 2022 by Duke University Press.)

Background: Drug manufacturers claim that the purpose of financial payments to physicians is to facilitate education about new drugs. This claim suggests 2 testable hypotheses: payments should not be associated with drug revenue and payments for each drug should decline over time as physicians become educated., Materials and Methods: We used open payments data on industry payments. We included payments for cancer drugs without generic/biosimilar competitors and used federal data sources to measure Medicare spending (a proxy for overall drug revenue) and a number of prescribers. We used generalized estimating equations (GEE) to model the drug-level association between industry payments and Medicare spending. Separately, we used GEE to estimate the change in payments with respect to the duration of time since initial FDA approval., Results: The sample included 89 drugs and 361 drug-year observations. The total value of industry payments for oncology drugs increased, from $53 333 854 in 2014 to $90 343 731 in 2018. There was no association between log-transformed mean, per-physician industry payments, and per-physician Medicare spending (estimate -0.001, 95%CI, -0.005 to 0.004). Payments for individual drugs decreased over time; estimated payments in the subsequent year for a drug with mean, per-physician payments of $1000 in the index year was: $681* for drugs 0-4 years since approval, $825 for 5-9 years, and $679* for ≥10 years (*P < .05)., Conclusions: Although industry-sponsored education may also serve marketing purposes, the absence of association between industry payments and Medicare spending and the decline in payments subsequent to approval are consistent with claims that industry payments function to facilitate physician education., (© The Author(s) 2022. Published by Oxford University Press.)

Background: The Prescription Drug User Fee Act (PDUFA) is due for reauthorization in 2022. Beyond creating the user fee program which now generates a majority of the Food and Drug Administration (FDA) Human Drugs Program budget, PDUFA has made numerous additional changes to FDA policy during its 29-year history. FDA's budgetary dependence on user fees may advantage the industry in negotiating favorable policy changes through PDUFA., Methods: The full texts of all prior PDUFA reauthorization bills and all submitted public comments and meeting minutes for the 2022 reauthorization were reviewed. Provisions affecting FDA regulatory authority and processes were identified., Findings: PDUFA legislation has instituted a broad range of changes to FDA policy, including evidentiary standards for drug approval, accelerated pathways for approval, industry involvement in FDA decision-making, rules regarding industry information dissemination to providers, and market entry of generic drugs. Negotiations over the 2022 reauthorization suggest that industry priorities include increased application of real-world evidence, regulatory certainty, and increased communication between FDA and industry during the drug application process., Conclusions: The need for PDUFA reauthorization every 5 years has created a recurring legislative vehicle through which far-ranging changes to FDA have been enacted, reshaping the agency's interactions and relationship with the regulated industry. The majority of policy changes enacted through PDUFA legislation have favored industry through decreasing regulatory standards, shortening approval times, and increasing industry involvement in FDA decision-making. FDA's budgetary dependence on the industry, the urgency of each PDUFA reauthorization's passage to maintain uninterrupted funding, and the industry's required participation in PDUFA negotiations may advantage the industry., Competing Interests: P.B.B. reports employment at Delphi Diagnostics, personal fees from Mercer, personal fees and nonfinancial support from United Rheumatology, personal fees from Foundation Medicine, personal fees from Grail, personal fees from Morgan Stanley, personal fees from NYS Rheumatology Society, personal fees and nonfinancial support from Oppenheimer & Co, personal fees from Cello Health, personal fees, nonfinancial support and other from Oncology Analytics, personal fees from Anthem, personal fees from Magellan Health, personal fees and nonfinancial support from Kaiser Permanente Institute for Health Policy, personal fees and nonfinancial support from Congressional Budget Office, personal fees and nonfinancial support from America’s Health Insurance Plans, grants from Kaiser Permanente, grants from Arnold Ventures, personal fees and nonfinancial support from Geisinger, personal fees from EQRx, personal fees from Meyer Cancer Center of Weill Cornell Medicine, and personal fees from National Pharmaceutical Council. The remaining authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)