The TELEhealth Shared decision-making Coaching and Navigation in Primary carE (TELESCOPE) intervention: a study protocol for delivering shared decision-making for lung cancer screening by patient navigators.

Background: Lung cancer screening (LCS) can reduce lung cancer mortality but has potential harms for patients. A shared decision-making (SDM) conversation about LCS is required by the Centers for Medicare & Medicaid Services (CMS) for LCS reimbursement. To overcome barriers to SDM in primary care, this protocol describes a telehealth decision coaching intervention for LCS in primary care clinics delivered by patient navigators. The objective of the study is to evaluate the effectiveness of the intervention and its implementation potential, compared with an enhanced usual care (EUC) arm. Methods: Patients (n = 420) of primary care clinicians (n = 120) are being recruited to a cluster randomized controlled trial. Clinicians are randomly assigned to 1) TELESCOPE intervention: prior to an upcoming non-acute clinic visit, patients participate in a telehealth decision coaching session about LCS delivered by trained patient navigators and nurse navigators place a low-dose CT scan (LDCT) order for each TELESCOPE patient wanting LCS, or 2) EUC: patients receive enhanced usual care from a clinician. Usual care is enhanced by providing clinicians in both arms with access to a Continuing Medical Education (CME) webinar about LCS and an LCS discussion guide. Patients complete surveys at baseline and 1-week after the scheduled clinic visit to assess quality of the SDM process. Re-navigation is attempted with TELESCOPE patients who have not completed the LDCT within 3 months. One month before being due for an annual screening, TELESCOPE patients whose initial LCS showed low-risk findings are randomly assigned to receive a telehealth decision coaching booster session with a navigator or no booster. Electronic health records are abstracted at 6, 12 and 18 months after the initial decision coaching session (TELESCOPE) or clinic visit (EUC) to assess initial and annual LCS uptake, imaging results, follow-up testing for abnormal findings, cancer diagnoses, treatment, and tobacco treatment referrals. This study will evaluate factors that facilitate or interfere with program implementation using mixed methods. Discussion: We will assess whether a decision coaching and patient navigation intervention can feasibly support high-quality SDM for LCS and guideline-concordant LCS uptake for patients in busy primary care practices serving diverse patient populations. Trial Registration: This study was registered at ClinicalTrials.gov (NCT05491213) on August 4, 2022.

The Association Between State Characteristics and Latinx People's Treated Hypertension in Established and New Latinx Destination States: A Multilevel Analysis.

This study sought to quantify the contributions of state-level factors including income inequality, state's legislature political control, and Medicaid expansion in new and established Latinx destination states on Latinx individuals' treated hypertension. Mixed-effects logistic regression analyses were conducted to analyze 2017 Behavioral Risk Factor Surveillance System data from 7524 Latinx adults nested within 39 states. Overall, 70% reported being pharmacologically treated for hypertension, and 66% resided in established destination states. Compared with Latinx people in established destination states, Latinx people in new destinations had lower odds of having treated hypertension (odds ratio [OR] = 0.72, 95% CI = 0.54-0.95). Within established Latinx destinations, the odds of treated hypertension were lower in states where legislatures expanded Medicaid than in states that did not expand Medicaid (OR = 0.84, 95% CI = 0.79-0.89). However, after controlling for the effects of individual-level factors, this association was no longer statistically significant. In new Latinx destination states, Medicaid expansion, legislatures' political control, and income inequality were not associated with treated hypertension. The study results highlight the importance of considering both individual- and state-level factors, as the interplay of such factors could hinder the successful implementation of cardiovascular risk reduction interventions.

Molecular and clinical effects of aromatase inhibitor therapy on skeletal muscle function in early-stage breast cancer.

We evaluated biochemical changes in skeletal muscle of women with breast cancer initiating aromatase inhibitors (AI), including oxidation of ryanodine receptor RyR1 and loss of stabilizing protein calstabin1, and detailed measures of muscle function. Fifteen postmenopausal women with stage I-III breast cancer planning to initiate AI enrolled. Quadriceps muscle biopsy, dual-energy x-ray absorptiometry, isokinetic dynamometry, Short Physical Performance Battery, grip strength, 6-min walk, patient-reported outcomes, and serologic measures of bone turnover were assessed before and after 6 months of AI. Post-AI exposure, oxidation of RyR1 significantly increased (0.23 ± 0.37 vs. 0.88 ± 0.80, p < 0.001) and RyR1-bound calstabin1 significantly decreased (1.69 ± 1.53 vs. 0.74 ± 0.85, p < 0.001), consistent with dysfunctional calcium channels in skeletal muscle. Grip strength significantly decreased at 6 months. No significant differences were seen in isokinetic dynamometry measures of muscle contractility, fatigue resistance, or muscle recovery post-AI exposure. However, there was significant correlation between oxidation of RyR1 with muscle power (r = 0.60, p = 0.02) and muscle fatigue (r = 0.57, p = 0.03). Estrogen deprivation therapy for breast cancer resulted in maladaptive changes in skeletal muscle, consistent with the biochemical signature of dysfunctional RyR1 calcium channels. Future studies will evaluate longer trajectories of muscle function change and include other high bone turnover states, such as bone metastases.

Adherence to Annual Lung Cancer Screening in a Centralized Academic Program.

BACKGROUND: Adherence to lung cancer screening (LCS) protocols is critical for achieving mortality reductions. However, adherence rates, particularly for recommended annual screening among patients with low-risk findings, are often sub-optimal. We evaluated annual LCS adherence for patients with low-risk findings participating in a centralized screening program at a tertiary academic center. PATIENTS AND METHODS: We conducted a retrospective, observational cohort study of a centralized lung cancer screening program launched in July 2018. We performed electronic medical review of 337 patients who underwent low-dose CT (LDCT) screening before February 1, 2021 (to ensure ≥ 15 months follow up) and had a low-risk Lung-RADS score of 1 or 2. Captured data included patient characteristics (smoking history, Fagerstrom score, environmental exposures, lung cancer risk score), LDCT imaging dates, and Lung-RADS results. The primary outcome measure was adherence to annual screening. We used multivariable logistic regression models to identify factors associated with adherence. RESULTS: Overall, 337 patients had an initial Lung-RADS result of 1 (n = 189) or 2 (n = 148). Among this cohort, 139 (73.5%) of Lung-RADS 1 and 111 (75.0%) of Lung-RADS 2 patients completed the annual repeat LDCT within 15 months, respectively. The only patient characteristic associated with adherence was having Medicaid coverage; compared to having private insurance, Medicaid patients were less adherent (adjusted OR = 0.37, 95% CI = 0.15-0.92). No other patient characteristic was associated with adherence. CONCLUSION: Our centralized screening program achieved a high initial annual adherence rate. Although LCS has first-dollar insurance coverage, other socioeconomic concerns may present barriers to annual screening for Medicaid recipients.

Implementing a Telehealth Shared Counseling and Decision-Making Visit for Lung Cancer Screening in a Veterans Affairs Medical Center.

Background: Veterans suffer substantial morbidity and mortality from lung cancer. Lung cancer screening (LCS) with low-dose computed tomography (LDCT) can reduce mortality. Guidelines recommend counseling and shared decision-making (SDM) to address the benefits and harms of screening and the importance of tobacco cessation before patients undergo screening. Observations: We implemented a centralized LCS program at the Iowa City Veterans Affairs Medical Center with a nurse program coordinator (NPC)-led telephone visit. Our multidisciplinary team ensured that veterans referred from primary care met eligibility criteria, that LDCT results were correctly coded by radiology, and that pulmonary promptly evaluated abnormal LDCT. The NPC mailed a decision aid to the veteran and scheduled a SDM telephone visit. We surveyed veterans after the visit using validated measures to assess knowledge, decisional conflict, and quality of decision making. We conducted 105 SDM visits, and 91 veterans agreed to LDCT. Overall, 84% of veterans reported no decisional conflict, and 59% reported high-quality decision making. While most veterans correctly answered questions about the harms of radiation, false-positive results, and overdiagnosis, few knew when to stop screening, and most overestimated the benefit of screening and the predictive value of an abnormal scan. Tobacco cessation interventions were offered to 72 currently smoking veterans. Conclusions: We successfully implemented an LCS program that provides SDM and tobacco cessation support using a centralized telehealth model. While veterans were confident about screening decisions, knowledge testing indicated important deficits, and many did not engage meaningfully in SDM. Clinicians should frame the decision as patient centered at the time of referral, highlight the importance of SDM, and be able to provide adequate decision support.

Location and Types of Treatment for Prostate Cancer After the Veterans Choice Program Implementation.

Importance: The Veterans Choice Program (VCP) was implemented in 2014 to help veterans gain broader access to specialized care outside of the Veterans Health Administration (VHA) facilities by providing them with purchased community care (CC). Objective: To describe the prevalence and patterns in VCP-funded purchased CC after the implementation of the VCP among veterans with prostate cancer. Design, Setting, and Participants: This cohort study used VHA administrative data on veterans with prostate cancer diagnosed between January 1, 2015, and December 31, 2018. These veterans were regular VHA primary care users. Analyses were performed from March to July 2023. Exposures: Driving distance (in miles) from residence to nearest VHA tertiary care facility. The location (VHA or purchased CC) in which treatment decisions were made was ascertained by considering 3 factors: (1) location of the diagnostic biopsy, (2) location of most of the postdiagnostic prostate-specific antigen laboratory testing, and (3) location of most of the postdiagnostic urological care encounters. Main Outcomes and Measures: The main outcome was receipt of definitive treatment and proportion of purchased CC by treatment type (radical prostatectomy [RP], radiotherapy [RT], or active surveillance) and by distance to nearest VHA tertiary care facility. Quality was evaluated based on receipt of definitive treatment for Gleason grade group 1 prostate cancer (low risk/limited treatment benefit by guidelines). Results: The cohort included 45 029 veterans (mean [SD] age, 67.1 [6.9] years) with newly diagnosed prostate cancer; of these patients, 28 866 (64.1%) underwent definitive treatment. Overall, 56.8% of patients received definitive treatment from the purchased CC setting, representing 37.5% of all RP care and 66.7% of all RT care received during the study period. Most patients who received active surveillance management (92.5%) remained within the VHA. Receipt of definitive treatment increased over the study period (from 5830 patients in 2015 to 9304 in 2018), with increased purchased CC for patients living farthest from VHA tertiary care facilities. The likelihood of receiving definitive treatment of Gleason grade group 1 prostate cancer was higher in the purchased CC setting (adjusted relative risk ratio, 1.79; 95% CI, 1.65-1.93). Conclusions and Relevance: This cohort study found that the percentage of veterans receiving definitive treatment in VCP-funded purchased CC settings increased significantly over the study period. Increased access, however, may come at the cost of low care quality (overtreatment) for low-risk prostate cancer.

Impact of Muscle Measures on Outcome in Patients Receiving Endocrine Therapy for Metastatic Breast Cancer: Analysis of ECOG-ACRIN E2112.

BACKGROUND: Observational data investigating the relationship between body habitus and outcomes in breast cancer have been variable and inconsistent, largely centered in the curative setting and focused on weight-based metrics. This study evaluated the impact of muscle measures on outcomes in patients with metastatic breast cancer receiving endocrine-based therapy. METHODS: Baseline CT scans were collected from ECOG-ACRIN E2112, a randomized phase III placebo-controlled study of exemestane with or without entinostat. A CT cross-sectional image at the L3 level was extracted to obtain skeletal muscle mass and attenuation. Low muscle mass (LMM) was defined as skeletal muscle index <41 cm2/m2 and low muscle attenuation (LMA) as muscle density <25 HU or <33 HU if overweight/obese by body mass index (BMI). Multivariable Cox proportional hazard models determined the association between LMM or LMA and progression-free survival (PFS) and overall survival (OS). Correlations between LMM, LMA, and patient-reported outcomes were determined using 2-sample t tests. RESULTS: Analyzable CT scans and follow-up data were available for 540 of 608 patients. LMM was present in 39% (n=212) of patients and LMA in 56% (n=301). Those with LMA were more likely to have obesity and worse performance status. LMM was not associated with survival (PFS hazard ratio [HR]: 1.13, P=.23; OS HR: 1.05, P=.68), nor was LMA (PFS HR: 1.01, P=.93; OS HR: 1.00, P=.99). BMI was not associated with survival. LMA, but not LMM, was associated with increased frequency of patient-reported muscle aches. CONCLUSIONS: Both low muscle mass and density are prevalent in patients with hormone receptor-positive metastatic breast cancer. Muscle measures correlated with obesity and performance status; however, neither muscle mass nor attenuation were associated with prognosis. Further work is needed to refine body composition measurements and select optimal cutoffs with meaningful endpoints in specific breast cancer populations, particularly those living with metastatic disease.

Evaluation of a Novel Question Prompt List in Pediatric Surgical Oncology.

INTRODUCTION: Parents of children with cancer describe interactions with clinicians as emotionally distressing. Patient engagement in treatment discussions decreases decisional conflict and improves decision quality which may limit such distress. We have shown that parents prefer to engage surgeons by asking questions, but parents may not know what to ask. Question Prompt Lists (QPLs), structured lists of questions designed to help patients ask important questions, have not been studied in pediatric surgery. We developed a QPL designed to empower parents to ask meaningful questions during pediatric surgical oncology discussions. We conducted a mixed methods analysis to assess the acceptability, appropriateness, and feasibility of using the QPL. METHODS: Key stakeholders at an academic children's hospital participated in focus groups to discuss the QPL. Focus groups were recorded and transcribed. Participants were surveyed regarding QPL acceptability, appropriateness, and feasibility. Thematic content analysis of transcripts was performed. RESULTS: Four parents, five nurses, five nurse practitioners, five oncologists, and four surgeons participated. Seven key themes were identified: (1) QPL as a tool of empowerment; (2) stick to the surgical details; (3) QPLs can impact discussion quality; (4) time consuming, but not overly disruptive; (5) parental emotion may impact QPL use; (6) provide QPLs prior to surgical consultation in both print and digital formats; and (7) expansion of QPLs to other disciplines. Over 70% of participants agreed that the QPL was acceptable, appropriate, and feasible. CONCLUSIONS: Our novel QPL is acceptable, appropriate, and feasible to use with parents of pediatric surgical oncology patients.

The influence of acute dietary nitrate supplementation on skeletal muscle fatigue and recovery in older women.

Older individuals fatigue more rapidly during, and recover more slowly from, dynamic exercise. Women are particularly vulnerable to these deleterious effects of aging, which increases their risk of falling. We have shown that dietary nitrate (NO3 - ), a source of nitric oxide (NO) via the NO3 - → nitrite (NO2 - ) → NO pathway, enhances muscle speed and power in older individuals in the non-fatigued state; however, it is unclear if it reduces fatigability and/or improves recoverability in this population. Using a double-blind, placebo-controlled, crossover design, we studied 18 older (age 70 ± 4 years) women who were administered an acute dose of beetroot juice (BRJ) containing either 15.6 ± 3.6 or <0.05 mmol of NO3 - . Blood samples were drawn throughout each ~3 h visit for plasma NO3 - and NO2 - analysis. Peak torque was measured during, and periodically for 10 min after, 50 maximal knee extensions performed at 3.14 rad/s on an isokinetic dynamometer. Ingestion of NO3 - -containing BRJ increased plasma NO3 - and NO2 - concentrations by 21 ± 8 and 4 ± 4 fold, respectively. However, there were no differences in muscle fatigue or recovery. Dietary NO3 - increases plasma NO3 - and NO2 - concentrations but does not reduce fatigability during or enhance recoverability after high intensity exercise in older women.

Significant Incidental Findings in the National Lung Screening Trial.

Importance: Low-dose computed tomography (LDCT) lung screening has been shown to reduce lung cancer mortality. Significant incidental findings (SIFs) have been widely reported in patients undergoing LDCT lung screening. However, the exact nature of these SIF findings has not been described. Objective: To describe SIFs reported in the LDCT arm of the National Lung Screening Trial and classify SIFs as reportable or not reportable to the referring clinician (RC) using the American College of Radiology's white papers on incidental findings. Design, Setting, and Participants: This was a retrospective case series study of 26 455 participants in the National Lung Screening Trial who underwent at least 1 screening examination with LDCT. The trial was conducted from 2002 to 2009, and data were collected at 33 US academic medical centers. Main Outcomes and Measures: Significant incident findings were defined as a final diagnosis of a negative screen result with significant abnormalities that were not suspicious for lung cancer or a positive screen result with emphysema, significant cardiovascular abnormality, or significant abnormality above or below the diaphragm. Results: Of 26 455 participants, 10 833 (41.0%) were women, the mean (SD) age was 61.4 (5.0) years, and there were 1179 (4.5%) Black, 470 (1.8%) Hispanic/Latino, and 24 123 (91.2%) White individuals. Participants were scheduled to undergo 3 screenings during the course of the trial; the present study included 75 126 LDCT screening examinations performed for 26 455 participants. A SIF was reported for 8954 (33.8%) of 26 455 participants who were screened with LDCT. Of screening tests with a SIF detected, 12 228 (89.1%) had a SIF considered reportable to the RC, with a higher proportion of reportable SIFs among those with a positive screen result for lung cancer (7632 [94.1%]) compared with those with a negative screen result (4596 [81.8%]). The most common SIFs reported included emphysema (8677 [43.0%] of 20 156 SIFs reported), coronary artery calcium (2432 [12.1%]), and masses or suspicious lesions (1493 [7.4%]). Masses included kidney (647 [3.2%]), liver (420 [2.1%]), adrenal (265 [1.3%]), and breast (161 [0.8%]) abnormalities. Classification was based on free-text comments; 2205 of 13 299 comments (16.6%) could not be classified. The hierarchical reporting of final diagnosis in NLST may have been associated with an overestimate of severe emphysema in participants with a positive screen result for lung cancer. Conclusions and Relevance: This case series study found that SIFs were commonly reported in the LDCT arm of the National Lung Screening Trial, and most of these SIFs were considered reportable to the RC and likely to require follow-up. Future screening trials should standardize SIF reporting.

Short-term beetroot juice supplementation improves muscle speed and power but does not reduce blood pressure or oxidative stress in 65-79 y old men and women.

We have previously demonstrated that acute ingestion of inorganic nitrate (NO3-)-rich beetroot juice (BRJ), a source of nitric oxide (NO) via the NO3- → nitrite (NO2-) → NO pathway, can improve muscle speed and power in older individuals. It is not known, however, whether this effect is maintained or perhaps even enhanced with repeated ingestion, or if tolerance develops as with organic nitrates, e.g., nitroglycerin. Using a double-blind, placebo-controlled, crossover design, we therefore studied 16 community-dwelling older (age 71 ± 5 y) individuals after both acute and short-term (i.e., daily for 2 wk) BRJ supplementation. Blood samples were drawn and blood pressure was measured periodically during each ∼3 h experiment, with muscle function determined using isokinetic dynamometry. Acute ingestion of BRJ containing 18.2 ± 6.2 mmol of NO3- increased plasma NO3- and NO2- concentrations 23 ± 11 and 2.7 ± 2.1-fold over placebo, respectively. This was accompanied by 5 ± 11% and 7 ± 13% increases in maximal knee extensor speed (Vmax) and power (Pmax), respectively. After daily supplementation for 2 wk, BRJ ingestion elevated NO3- and NO2- levels 24 ± 12 and 3.3 ± 4.0-fold, respectively, whereas Vmax and Pmax were 7 ± 9% and 9 ± 11% higher than baseline. No changes were observed in blood pressure or in plasma markers of oxidative stress with either acute or short-term NO3- supplementation. We conclude that both acute and short-term dietary NO3- supplementation result in similar improvements in muscle function in older individuals. The magnitudes of these improvements are sufficient to offset the decline resulting from a decade or more of aging and are therefore likely to be clinically significant.

Review of the Food and Drug Administration's Center for Drug Evaluation and Research Program for New Molecular Entities: Trends and Regulatory Requirements in Mid-Cycle Communications.

The United States Food and Drug Administration (FDA) implemented "the Program" in 2012 to promote greater transparency and increased communication between the FDA and applicants of New Molecular Entity (NME) New Drug Applications (NDA) and original Biologics License Applications (BLA). We examined 128 publicly available NME NDA and original BLA approval packages reviewed and approved under the Program with the goal to educate regulatory professionals about the content and timing of communications from FDA to the Sponsor. This research found that the timing of communications between FDA and the Sponsor through the Mid-Cycle Communication (MCC) was consistent with the 21st-century Desk Reference Guide (DRG); 90% of internal FDA Mid-Cycle Meetings, MCCs with the applicant, and corresponding issuance of MCC minutes were within the target date. The content and format of the MCC were also consistent with the DRG and across disciplines. Almost all MCCs reviewed included a discussion on significant review issues, including major safety concerns. FDA's preliminary opinion on the necessity of a Risk Evaluation and Mitigation Strategy (REMS), which was predictive of REMS requirement at approval. The FDA's MCC comment on advisory committee meeting plans was highly predictive; if the MCC indicated an AC was planned, an AC meeting was held 91% of the time. With respect to the MCC, this research found the DRG and relevant FDA Manual of Policies and Procedures to be reliable resources to predict the FDA's planned actions associated with the review of a NME NDA or original BLA.

After PSA screening, MRI-targeted vs. systematic biopsy detected fewer clinically insignificant prostate cancers.

SOURCE CITATION: Hugosson J, Månsson M, Wallström J, et al. Prostate cancer screening with PSA and MRI followed by targeted biopsy only. N Engl J Med. 2022;387:2126-37. 36477032.

Timely Curative Treatment and Overall Mortality Among Veterans With Stage I NSCLC.

Introduction: Early stage lung cancer (LC) outcomes depend on the receipt of timely therapy. We aimed to determine the proportions of Veterans with stage I NSCLC in the age group eligible for LC screening (LCS) receiving timely curative treatment (≤12 wk after diagnosis), the factors associated with timely treatment and modality, and the factors associated with overall mortality. Methods: Retrospective cohort study in Veterans aged 55 to 80 years when diagnosed with stage I NSCLC during 2011 to 2015. We used multivariate logistic regression models to determine factors associated with receiving timely therapy and receiving surgery versus stereotactic body radiation therapy (SBRT). We used multivariate Cox proportional hazards regression analysis to determine factors associated with overall mortality. Results: We identified 4796 Veterans with stage I NSCLC; the cohort was predominantly older, White males, current or former smokers, and living in urban areas. Overall, 84% underwent surgery and 16% underwent SBRT. The median time to treatment was 63 days (61 d for surgery; 71 d for SBRT), with 30% treated more than 12 weeks. Unmarried Veterans with higher social deprivation index were less likely to receive timely therapy. Black race, female sex, and never smoking were associated with lower overall mortality. Older Veterans receiving treatment >12 wk, with higher comorbidity index, and squamous cell carcinoma had higher overall mortality. Conclusions: A total of 30% of the Veterans with stage I NSCLC in the age group eligible for LCS received curative treatment more than 12 weeks after diagnosis, which was associated with higher overall mortality. Delays in LC treatment could decrease the mortality benefits of LCS among the Veterans.