Longitudinal quality of life after sublobar resection and stereotactic body radiation therapy for early-stage non-small cell lung cancer.

BACKGROUND: Many patients with early-stage lung cancer are not candidates for lobectomy because of various factors, with treatment options including sublobar resection or stereotactic body radiation therapy (SBRT). Limited information exists regarding patient-centered outcomes after these treatments. METHODS: Subjects with stage I-IIA non-small cell lung cancer (NSCLC) at high risk for lobectomy who underwent treatment with sublobar resection or SBRT were recruited from five medical centers. Quality of life (QOL) was compared with the Short Form 8 (SF-8) for physical and mental health and Functional Assessment of Cancer Therapy-Lung (FACT-L) surveys at baseline (pretreatment) and 7 days, 30 days, 6 months, and 12 months after treatment. Propensity score methods were used to control for confounders. RESULTS: Of 337 subjects enrolled before treatment, 63% received SBRT. Among patients undergoing resection, 89% underwent minimally invasive video-assisted thoracic surgery or robot-assisted resection. Adjusted analyses showed that SBRT-treated patients had both higher physical health SF-8 scores (difference in differences [DID], 6.42; p = .0008) and FACT-L scores (DID, 2.47; p = .004) at 7 days posttreatment. Mental health SF-8 scores were not different at 7 days (p = .06). There were no significant differences in QOL at other time points, and all QOL scores returned to baseline by 12 months for both groups. CONCLUSIONS: SBRT is associated with better QOL immediately posttreatment compared with sublobar resection. However, both treatment groups reported similar QOL at later time points, with a return to baseline QOL. These findings suggest that sublobar resection and SBRT have a similar impact on the QOL of patients with early-stage lung cancer deemed ineligible for lobectomy.

Greater executive dysfunction in patients post-COVID-19 compared to those not infected.

BACKGROUND: A number of patients post-coronavirus disease-19 (COVID-19) report cognitive impairment (CI), even months after acute infection. We aimed to assess if COVID-19 is associated with increased incidence of CI in comparison to controls. METHODS: We analyzed data from the Mount Sinai Health System Post-COVID-19 Registry in New York City, a prospective cohort of patients post-COVID-19 ≥18 years of age and non-infected controls. CI was defined by scores ≥ 1.0 standard deviation below population norms, and was assessed using well-validated measures of attention, working memory, processing speed, executive functioning/cognitive flexibility, language, learning, and memory. Logistic regression models assessed odds for CI in each domain in patients post-COVID-19 vs. controls after adjusting for potential confounders. In exploratory analyses, we assessed odds for CI by site of acute COVID-19 care as a proxy for disease severity. FINDINGS: 417 patients post-COVID-19 and 151 controls (mean age 49 years, 63% female, 21% Black, 17% Latinx) were included. In adjusted analyses, patients were significantly more likely than controls to have CI in executive functioning (odds ratio [OR]: 2.19; 95% confidence interval [CI]: 1.03 to 4.67), particularly those treated in outpatient (OR: 2.22; 95% CI: 1.02 to 4.82) and inpatient hospital (OR: 3.59; 95% CI: 1.27 to 10.16) settings. There were no significant associations between CI in other domains and history of COVID-19 or site of acute care. INTERPRETATION: Patients post-COVID-19 have greater odds of executive dysfunction, suggesting that focused cognitive screening may be prudent, even in those with mild to moderate disease. Studies should explore the pathophysiology and potential treatments for CI in this population. FUNDING: This work was funded by the Icahn School of Medicine at Mount Sinai.

Prostate Cancer Screening and Incidence among Aging Persons Living with HIV.

PURPOSE: The risk of prostate cancer among persons living with human immunodeficiency virus (PWH) is not well understood and may be obscured by different opportunities for detection. MATERIALS AND METHODS: We identified 123,472 (37,819 PWH and 85,653 comparators) men enrolled in the Veterans Aging Cohort Study, a prospective national cohort of PWH and demographically matched, uninfected comparators in 2000-2015. We calculated rates of prostate specific antigen (PSA) testing by human immunodeficiency virus (HIV) status and fit multivariable Poisson models comparing the rates of PSA testing, prostate biopsy, and cancer incidence. RESULTS: The mean age at enrollment was 52 years. Rates of PSA testing were lower in PWH versus uninfected comparators (0.58 versus 0.63 tests per person-year). Adjusted rates of PSA screening and prostate biopsy were lower among PWH (incidence rate ratio [IRR] 0.87, 95% CI 0.75-0.84 and IRR 0.79 95% CI 0.74-0.83, respectively). The crude IRR for prostate cancer was lower in PWH versus controls (IRR 0.90, 95% CI 0.83-0.97). However, in a multivariable model adjusting for PSA testing, cancer incidence was similar by HIV status (IRR=0.93, 95% CI 0.86-1.01, p=0.08). Among patients who received a prostate biopsy, incidence of prostate cancer did not differ significantly by HIV status (IRR 1.06, 95% CI 0.98-1.15, p=0.15). Among incident cancers, there were significant differences in the distributions of Gleason grade (p=0.05), but not cancer stage (p=0.14) by HIV status. CONCLUSIONS: When accounting for less PSA testing among PWH, the incidence of prostate cancer was similar by HIV status. These findings suggest that less screening contributed to lower observed incidence of prostate cancer in PWH.

Paediatric integrated care in the primary care setting: A scoping review of populations served, models used and outcomes measured.

BACKGROUND: Paediatric integrated care (PIC), which involves primary care and behavioural health clinicians working together with patients and families, has been promoted as a best practice in the provision of care. In this context, behavioural health includes behavioural elements in the care of mental health and substance abuse conditions, chronic illness and physical symptoms associated with stress, and addressing health behaviours. Models of and contexts in which PIC has been applied vary, as do the outcomes and measures used to determine its value. Thus, this study seeks to better understand (1) what paediatric subpopulations are receiving integrated care, (2) which models of PIC are being studied, (3) what PIC outcomes are being explored and what measures and strategies are being used to assess those outcomes, and (4) whether the various models are resulting in positive outcomes. These questions have significant policy and clinical implications, given current national- and state-level efforts aimed at promoting integrated health care. METHODS: This study utilized Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews to identify relevant articles published between January 1994 and 30 June 2020. The search utilized three databases: PubMed, PsycInfo and CINAHL. A total of 28 articles met the eligibility criteria for inclusion. RESULTS: Overall, acceptability of PIC appears to be high for patients and providers, with access, screening and engagement generally increasing. However, several gaps in the knowledge base on PIC were uncovered, and for some studies, ascertaining which models of integrated care were being implemented proved difficult. CONCLUSION: PIC has the potential to improve access to and quality of behavioural health care, but more research is needed to understand what models of PIC prove most beneficial and which policies and conditions promote cost efficiency. Rigorous evaluation of patient outcomes, provider training, institutional buy-in and system-level changes are needed.

Electrocautery ablation of anal high-grade squamous intraepithelial lesions: Effectiveness and key factors associated with outcomes.

BACKGROUND: Electrocautery ablation (EA) is a common treatment modality for patients with anal high-grade squamous intraepithelial lesions (HSILs), but to the authors' knowledge its effectiveness has been understudied. The objective of the current study was to determine ablation outcomes and to identify clinicopathological factors associated with postablation disease recurrence. METHODS: A total of 330 people living with HIV with de novo intra-anal HSIL who were treated with EA from 2009 to 2016 were studied retrospectively. Using long-term, surveillance high-resolution anoscopy biopsy data, treatment failures were classified as local recurrence (HSIL noted at the treated site at the time of surveillance) or overall recurrence (HSIL noted at treated or untreated sites). The associations between these outcomes and clinical factors were analyzed using Cox proportional hazards models. RESULTS: Approximately 88% of participants were men who have sex with men. The median age of study  participants was 45.5 years (range, 35-51 years) and approximately 49% had multiple index HSILs (range, 2-6 index HSILs). At a median of 12.2 months postablation (range, 6.3-20.9 months postablation), approximately 45% of participants had developed local recurrence whereas 60% had developed overall recurrence. Current cigarette smoking, HIV viremia (HIV-1 RNA ≥100 copies/mL), and multiple index HSILs were found to be predictive of local recurrence. Overall recurrence was more common in current smokers and those with multiple index lesions. In multivariable models that included human papillomavirus (HPV) genotypes, baseline and persistent infections with HPV-16 and/or HPV-18 were found to be significantly associated with both local and overall recurrence. CONCLUSIONS: EA is an effective treatment modality for anal HSIL in people living with HIV, but rates of disease recurrence are substantial. Multiple index HSILs, HIV viremia, current cigarette smoking, and both baseline and persistent infection with HPV-16 and/or HPV-18 appear to negatively impact treatment success. Ongoing surveillance is imperative to capture recurrence early and improve long-term treatment outcomes.

Predicting Pediatric Emergency Severity Index Level Based on Emergency Department Pre-Arrival Information.

PURPOSE: This study examines the use of phone referral information to predict Emergency Severity Index triage levels as a proxy to anticipate emergency department nursing resource allocation in a pediatric hospital. It also assesses the relationship between these pre-arrival triage levels and hospital admission. DESIGN AND METHODS: Emergency nurses with specialized training used standardized phone referral information to assign triage levels to 481 patients before their arrival. Upon patient arrival, independent triage levels were assigned. The two levels were then compared and patient disposition was collected. Descriptive statistics and Cohen's kappa were used to assess agreement between the two emergency severity index levels. RESULTS: Moderate agreement was found between the pre-arrival and arrival triage levels. The majority of patients (71.3%) with a pre-arrival triage level of 1 or 2 (the most acute levels) were admitted to the hospital. These patients were also more likely to be admitted to the intensive care unit than were patients with a pre-arrival triage level≥3. CONCLUSIONS AND PRACTICE IMPLICATIONS: The ability to predict triage levels for incoming patients could give the emergency department charge nurse the ability to plan ahead so that appropriate nursing staffing is available upon arrival. The knowledge that patients assigned a pre-arrival triage level of 1 or 2 are more likely to be admitted gives the emergency department the ability to plan for bed placement and inpatient nursing resources earlier, potentially resulting in decreased emergency department length of stay. More study on these potential benefits is needed.

Infected Congenital Epicardial Cyst Presenting as Acute Abdomen.

A previously healthy 3-year-old boy presented to the emergency department with abdominal pain, fever, and emesis. Laboratory and radiologic evaluation for causes of acute abdomen were negative; however, review of the abdominal x-ray demonstrated cardiomegaly with the subsequent diagnosis of pericardial cyst by echocardiogram and computed tomography. The patient underwent surgical decompression and attempted removal of the cystic structure revealing that the cyst originated from the epicardium. His abdominal pain and fever resolved postoperatively and he completed a 3-week course of ceftriaxone for treatment of Propionibacterium acnes infected congenital epicardial cyst. Emergency department physicians must maintain a broad differential in patients with symptoms of acute abdomen to prevent complications from serious cardiac or pulmonary diseases that present with symptoms of referred abdominal pain.

A Review of Anatomy, Physiology, and Benign Pathology of the Nipple.

The nipple and areola are pigmented areas of modified skin that connect with the underlying gland of the breast via ducts. The fairly common congenital anomalies of the nipple include inversion, clefts, and supernumerary nipples. The anatomy of the nipple areolar complex is discussed as a foundation to review anatomical variants, and the physiologic development of the nipple, including changes in puberty and pregnancy, as well as the basis of normal physiologic discharge, are addressed. Skin conditions affecting the nipple include eczema, which, while similar to eczema occurring elsewhere on the body, poses unique aspects in terms of diagnosis and treatment. This article concludes with discussion on the benign abnormalities that develop within the nipple, including intraductal papilloma and nipple adenoma.

Comparison of Stage I Non-Small-Cell Lung Cancer Treatments for Patients Living With HIV: A Simulation Study.

INTRODUCTION: Non-small-cell lung cancer (NSCLC) is a leading cause of death for people living with HIV (PWH). Nevertheless, there are no clinical trial data regarding the management of early-stage lung cancer in PWH. Using data from large HIV and cancer cohorts we parameterized a simulation model to compare treatments for stage I NSCLC according to patient characteristics. MATERIALS AND METHODS: To parameterize the model we analyzed PWH and NSCLC patient outcomes and quality of life data from several large cohort studies. Comparative effectiveness of 4 stage I NSCLC treatments (lobectomy, segmentectomy, wedge resection, and stereotactic body radiotherapy) was estimated using evidence synthesis methods. We then simulated trials comparing treatments according to quality adjusted life year (QALY) gains by age, tumor size and histology, HIV disease characteristics and major comorbidities. RESULTS: Lobectomy and segmentectomy yielded the greatest QALY gains among all simulated age, tumor size and comorbidity groups. Optimal treatment strategies differed by patient sex, age, and HIV disease status; wedge resection was among the optimal strategies for women aged 80 to 84 years with tumors 0 to 2 cm in size. Stereotactic body radiotherapy was included in some optimal strategies for patients aged 80 to 84 years with multimorbidity and in sensitivity analyses was a non-inferior option for many older patients or those with poor HIV disease control. CONCLUSION: In simulated comparative trials of treatments for stage I NSCLC in PWH, extensive surgical resection was often associated with the greatest projected QALY gains although less aggressive strategies were predicted to be non-inferior in some older, comorbid patient groups.

Strategic Surge Responses in the COVID-19 era: Operational Themes, Innovative Solutions and Lessons Learned by Three Freestanding Pediatric Emergency Departments.

The prolonged COVID-19 pandemic has created unique and complex challenges in operational and capacity planning for pediatric emergency departments, as initial low pediatric patient volumes gave way to unpredictable patient surges during Delta and Omicron variants. Compounded by widespread hospital supply chain issues, staffing shortages due to infection and attrition, and a concurrent pediatric mental health crisis, the surges have pushed pediatric emergency department leaders to re-examine traditionally defined clinical processes, and adopt innovative operational strategies. This study describes the strategic surge response and lessons learned by 3 major freestanding academic pediatric emergency departments in the western United States to help inform current and future pediatric pandemic preparedness.

Intraoperative Fluorescence Guidance for Breast Cancer Lumpectomy Surgery.

BACKGROUND: Although lumpectomy and mastectomy provide equivalent survival for patients with breast cancer, local recurrence after lumpectomy increases breast cancer mortality. Positive lumpectomy margins, which imply incomplete tumor removal, are the strongest predictor of local recurrence and are identified days after surgery, necessitating a second surgery. METHODS: In this prospective trial, we assessed margin status with or without pegulicianine fluorescence-guided surgery (pFGS) for stages 0 to 3 breast cancers. To prevent surgeons from performing smaller than standard lumpectomies in anticipation of pFGS assistance, patients were randomly assigned 10:1 to pFGS or control groups, thus randomization was not designed to provide a control group for evaluating device performance. In patients undergoing pFGS, additional pFGS-guided cavity margins were excised at sites of pegulicianine signal. We evaluated three coprimary end points: the percentage of patients for whom pFGS-guided margins contained cancer, sensitivity, and specificity. RESULTS: Overall, 406 patients received 1.0 mg/kg intravenous pegulicianine followed by lumpectomy. Among 392 patients randomly assigned, 316 had invasive cancers, and 76 had in situ cancers. In 27 of 357 patients undergoing pFGS, pFGS-guided margins removed tumor left behind after standard lumpectomy, 22 from cavity orientations deemed negative on standard margin evaluation. Second surgeries were avoided by pFGS in 9 of 62 patients with positive margins. On per-margin analysis, pFGS specificity was 85.2%, and sensitivity was 49.3%. Pegulicianine administration was stopped for adverse events in six patients. Two patients had grade 3 serious adverse events related to pegulicianine. CONCLUSIONS: The use of pFGS in breast cancer surgery met prespecified thresholds for removal of residual tumor and specificity but did not meet the prespecified threshold for sensitivity. (Funded by Lumicell, Inc. and the National Institutes of Health; Clinicaltrials.gov number, NCT03686215.)

Factors Affecting Implementation of Simulation-Based Education After Faculty Training in a Low-Resource Setting.

INTRODUCTION: Simulation instructor training is a recognized key component of health care simulation implementation, including in low-resource settings. PediSTARS India (Pediatric Simulation Training and Research Society) has developed and delivered several instructor training courses and more recently a 3-level faculty development program. However, there is variability in adoption of simulation at workplaces. The goal of this study was to identify factors that influence translation of instructor training into workplace simulation. METHODS: At the conclusion of their faculty development program, participants of the 2018 PediSTARS simulation instructor workshop were invited to participate in a qualitative study with an online questionnaire followed by a semistructured interview. The 3 key questions explored the "enablers," "barriers," and "changes needed" at workplaces for simulation-based training. The responses were analyzed and classified into broad themes. RESULTS: Of the 76 participants of the workshop, 11 were interviewed. The enablers were classified under 3 themes; "management support," "trained team" and "smart sourcing." Barriers were "lack of infrastructure," "lack of time," and "lack of simulation culture." The proposed changes were to "raise awareness," "strengthen systems," and "curricular integration." CONCLUSIONS: This study demonstrates the importance of institutional leadership support for simulation-based training and also that new instructors should focus on training teams in the workplace and mapping simulation activities to existing curricula. These results have wide applicability to a variety of health care settings and instructor training programs. Collaboration between organizations for further research about the impact of simulation-based training on patient safety and outcomes is also required.

Evolution of a Simulation Faculty Development Program in a Low-Resource Setting.

SUMMARY STATEMENT: The PediSTARS Faculty Development Program is a novel approach for simulation faculty training with an aim to increase the pool of trained simulation faculty in India and neighboring countries that could then facilitate simulation-based training, both at their own workplaces and in the PediSTARS simulation-based workshops that provide training in pediatric and neonatal emergencies. This commentary describes the evolution of the faculty development program, the initial process, the feedback obtained, the changes undertaken, the progress made to date, and the challenges ahead. There is also an emphasis on the key generalizable principles that can be applicable to other low-resource settings.

Description of Audiologic, Developmental, Ophthalmologic, and Neurologic Diagnoses at a Primary Care Clinic for Children in Foster Care.

OBJECTIVES: This study aimed to describe the prevalence of medically diagnosed audiologic, developmental, ophthalmologic, and neurologic conditions in a foster care primary care clinic and to identify any associations among these diagnoses and patient characteristics, placement type, and maltreatment type. METHODS: This study used the electronic medical records for patients (n = 4977), aged 0 to 20 years, with at least 1 visit to an academic-affiliated medical center primary care clinic exclusively serving children in foster care between January 1, 2017, and December 31, 2020. This study was a retrospective chart review. Descriptive statistics were calculated. Bivariate logistic regression analysis was used to determine associations between the outcome variables and each independent variable. Multivariable logistic regression analysis was performed using only significant independent variables from the bivariate analysis. RESULTS: Overall, 3.5% of children had an audiologic diagnosis, 42% had a developmental diagnosis, 9.0% had an ophthalmologic diagnosis, and 4.5% had a neurologic diagnosis. There were increased odds of developmental delay with child neglect and medical complexity and decreased odds with Hispanic ethnicity, Black race, female sex, obesity, and shelter placement. CONCLUSION: These findings add to the limited data regarding medically diagnosed audiologic, developmental, ophthalmologic, and neurologic conditions for children in foster care in a primary care setting. A medical home may help children in foster care, who experience many barriers to comprehensive health care, to better identify and address these health conditions. Future studies are needed that examine health outcomes of children in foster care with these health conditions followed in a medical home.

Optimizing the use of adjuvant chemotherapy in non-small cell lung cancer patients with comorbidities.

Veterans with locoregional non-small cell lung cancer (NSCLC) may benefit from adjuvant chemotherapy. However, comorbidities and other factors may impact the harms and benefits of this treatment. Here, we identified the optimal indications for adjuvant chemotherapy in Veterans with NSCLC, chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), and/or coronary artery disease (CAD). We used data from randomized controlled trials (RCTs) and Veterans Administration (VA) databases to enhance a simulation model. Then, we conducted in-silico RCTs comparing adjuvant chemotherapy vs observation among Veterans with stage II-IIIA NSCLC. Among Veterans without COPD or CKD, adjuvant chemotherapy was the optimal strategy regardless of the presence or absence of CAD except for patients >70 years with squamous cell carcinoma. Conversely, most veterans without COPD but with CKD were optimally managed with observation. Veterans with COPD but without CKD, benefited from adjuvant chemotherapy if they were ≤70 years with stage II-IIIA adenocarcinoma or <60 years with stage II-IIIA squamous cell carcinoma. Adjuvant chemotherapy was only beneficial for Veterans with both COPD and CKD among stage II-IIIA adenocarcinoma <60 years of age. Veterans with stages II-IIIA squamous cell carcinoma, COPD, and CKD were optimally managed with observation. Many Veterans with comorbidities are optimally managed with observation post-surgical resection. However, we also identified several groups of Veterans whom the benefits of adjuvant chemotherapy outweighed the risks of early toxicity. Our findings could inform patient-provider discussions and potentially reduce physicians' uncertainty about the role of adjuvant chemotherapy in this population.

Lung cancer incidence among world trade center rescue and recovery workers.

BACKGROUND: Many World Trade Center disaster (WTC) rescue and recovery workers (WTC RRWV) were exposed to toxic inhalable particles. The impact of WTC exposures on lung cancer risk is unclear. METHODS: Data from the WTC Health Program General Responders Cohort (WTCGRC) were linked to health information from a large New York City health system to identify incident lung cancer cases. Incidence rates for lung cancer were then calculated. As a comparison group, we created a microsimulation model that generated expected lung cancer incidence rates for a WTC- and occupationally-unexposed cohort with similar characteristics. We also fitted a Poisson regression model to determine specific lung cancer risk factors for WTC RRWV. RESULTS: The incidence of lung cancer for WTC RRWV was 39.5 (95% confidence interval [CI]: 30.7-49.9) per 100,000 person-years. When compared to the simulated unexposed cohort, no significant elevation in incidence was found among WTC RRWV (incidence rate ratio [IRR] 1.34; 95% CI: 0.92-1.96). Predictors of lung cancer incidence included age, smoking intensity, and years since quitting for former smokers. In adjusted models evaluating airway obstruction and individual pre-WTC occupational exposures, only mineral dust work was associated with lung cancer risk (IRR: 2.03; 95% CI: 1.07-3.86). DISCUSSION: In a sample from a large, prospective cohort of WTC RRWV we found a lung cancer incidence rate that was similar to that expected of a WTC- and occupationally-unexposed cohort with similar individual risk profiles. Guideline-concordant lung cancer surveillance and periodic evaluations of population-level lung cancer risk should continue in this group.

Adverse Events Following Limited Resection versus Stereotactic Body Radiation Therapy for Early Stage Lung Cancer.

Rationale: Approximately a quarter of patients with early stage lung cancer are not medically fit for lobectomy. Limited resection and stereotactic body radiation therapy (SBRT) have emerged as alternatives for these patients. Given the equipoise on the effectiveness of the two treatments, treatment-related adverse events (AEs) could have a significant impact on patients' decision-making and treatment outcomes. Objectives: To compare the AE profile between SBRT versus limited resection. Methods: Data were derived from a prospective cohort of patients with stage I-IIA non-small cell lung cancer who were deemed as high-risk for lobectomy recruited from five centers across the United States. Propensity scores and inverse probability weighting were used to compare the rates of 30- and 90-day AEs among patients treated with limited resection versus SBRT. Results: Overall, 65% of 252 patients underwent SBRT. After adjusting for propensity scores, there was no significant difference in developing at least one AE comparing SBRT to limited resection (odds ratio [OR]: 1.00; 95% confidence interval [CI]: 0.65-1.55 and OR: 1.27; 95% CI: 0.84-1.91 at 30 and 90 days, respectively). SBRT was associated with lower risk of infectious AEs than limited resection at 30 days (OR: 0.05; 95% CI: 0.01-0.39) and 90 days posttreatment (OR: 0.41; 95% CI: 0.17-0.98). Additionally, SBRT was associated with persistently elevated risk of fatigue (OR: 2.47; 95% CI: 1.34-4.54 at 30 days and OR: 2.69; 95% CI: 1.52-4.77 at 90 days, respectively), but significantly lower risks of respiratory AEs (OR: 0.36; 95% CI: 0.20-0.65 and OR: 0.51; 95% CI: 0.31-0.86 at 30 and 90 days, respectively). Conclusions: Though equivalent in developing at least one AE, we found that SBRT is associated with less toxicity than limited resection in terms of infectious and respiratory AEs but higher rates of fatigue that persisted up to 3 months posttreatment. This information, combined with data about oncologic effectiveness, can help patients' decision-making regarding these alternative therapies.