Mitophagy Controls the Activities of Tumor Suppressor p53 to Regulate Hepatic Cancer Stem Cells.

Autophagy is required for benign hepatic tumors to progress into malignant hepatocellular carcinoma. However, the mechanism is unclear. Here, we report that mitophagy, the selective removal of mitochondria by autophagy, positively regulates hepatic cancer stem cells (CSCs) by suppressing the tumor suppressor p53. When mitophagy is enhanced, p53 co-localizes with mitochondria and is removed by a mitophagy-dependent manner. However, when mitophagy is inhibited, p53 is phosphorylated at serine-392 by PINK1, a kinase associated with mitophagy, on mitochondria and translocated into the nucleus, where it binds to the NANOG promoter to prevent OCT4 and SOX2 transcription factors from activating the expression of NANOG, a transcription factor critical for maintaining the stemness and the self-renewal ability of CSCs, resulting in the reduction of hepatic CSC populations. These results demonstrate that mitophagy controls the activities of p53 to maintain hepatic CSCs and provide an explanation as to why autophagy is required to promote hepatocarcinogenesis.

Performance measurement part I: Foundational knowledge for measure development.

As medicine is moving toward performance and outcome-based payment and is transitioning away from productivity-based systems, value is now being appraised in healthcare through "performance measures." Over the past few decades, assessment of clinical performance in health care has been essential in ensuring safe and cost-effective patient care. The Centers for Medicare & Medicaid Services is further driving this change with measurable, outcomes-based national payer incentive payment systems. With the continually evolving requirements in health care reform focused on value-based care, there is a growing concern that clinicians, particularly dermatologists, may not understand the scientific rationale of health care quality measurement. As such, in order to help dermatologists understand the health care measurement science landscape to empower them to engage in the performance measure development and implementation process, the first article in this 2-part continuing medical education series reviews the value equation, historic and evolving policy issues, and the American Academy of Dermatology's approach to performance measurement development to provide the required foundational knowledge for performance measure developers.

Performance measurement part II: A guide to developing dermatology performance measures.

Throughout the 21st century, national and local governments, private health sectors, health insurance companies, healthcare professionals, labor unions, and consumers have been striving to develop an effective approach to evaluate, report, and improve the quality of healthcare. As medicine improves and health systems grow to meet patient needs, the performance measurement system of care effectiveness must also evolve. Continual efforts should be undertaken to effectively measure quality of care to create a more informed public, improve health outcomes, and reduce healthcare costs. As such, recent policy reform has necessitated that performance systems be implemented in healthcare, with the "performance measure" being the foundation of the system in which all of healthcare must be actively engaged in to ensure optimal care for patients. The development of performance measures can be highly complex, particularly when creating specialty-specific performance measures. To help dermatologists understand the process of creating dermatology-specific performance measures to engage in creating or implementing performance measures at the local or national levels, this article in the two-part continuing medical education series reviews the types, components, and process of developing, reviewing, and implementing performance measures.

Initial experience with enhanced recovery after surgery (ERAS) and early discharge protocols after robotic extended totally extraperitoneal (eTEP) hernia surgery.

BACKGROUND: Though robotic adoption for eTEP surgery has decreased technical barriers to minimally invasive repairs of large ventral hernias, relatively few studies have examined outcomes of robotic-specific eTEP surgery. This study evaluates safety, feasibility, and early outcomes of ERAS/same-day discharge protocols for robotic eTEP ventral hernia repairs. METHODS: A retrospective chart review was performed for all robotic eTEP hernia surgeries at a single institution between 2019 and 2022. Analysis included patient demographics, hernia characteristics, intraoperative data, and post-operative outcomes at 30 days. ERAS protocol included: judicious use of urinary catheters with removal at end of case if placed, bilateral transversus abdominus plane (TAP) blocks, post-operative abdominal wall binder, and opioid-sparing perioperative analgesia. Patients were discharged same day from post-anesthesia care unit (PACU) if they lacked comorbidities requiring observation post-anesthesia and demonstrated stable vital signs, adequate pain control, ability to void, and ability to ambulate. Hospital length of stay (LOS) was considered 0 for same-day PACU discharges or hospitalizations < 24 h. RESULTS: 102 patients were included in this case series. 69% (70/102) of patients were discharged same-day (mean LOS 0.47 ± 0.80 days). Within 30 post-operative days, 3% (3/102) of patients presented to the ER, 2% (2/102) were readmitted to the hospital, and 1% (1/102) required reoperation. There was 1 serious complication (Clavien-Dindo grade 3/4) with an aggregate complication rate of 7.8%. CONCLUSIONS: Our initial experience with ERAS protocols and same-day discharges after robotic eTEP repair demonstrates this approach is safe and feasible with acceptable short-term patient outcomes. Compared to traditional open surgery for large ventral hernias, robotic eTEP may enable significant reductions in hospital LOS as adoption increases.

The modern anesthesiologist's manual: the development and maintenance of an anesthesia case reference application.

Anesthesia clinicians care for patients undergoing a wide range of procedures, making access to reliable references crucial. However, existing resources have key limitations. This technical report describes the development of an in-house anesthesia case reference application designed for use in a tertiary academic hospital. Additionally, it details our experiences in maintaining this system over a 22-month period and compares this system to alternative resources. Utilizing JavaScript and the React library, we developed a cross-platform perioperative reference application. Over fifty articles, encompassing anesthetic considerations for various surgical disciplines, have been created. Furthermore, we conducted a preliminary analysis of analytics data. In the 22 months since the application's inception, the application has garnered over 22,000 views from local users. While there are more than 150 registered users, the number of unregistered users accessing the application on the hospital network remains unknown. Notably, 70% of users accessed the application through a mobile device. The most popular articles centered around procedures with diverse and specific surgeon preferences. Currently, the reported case reference application is routinely utilized by anesthesia clinicians at our institution. Future endeavors will concentrate on establishing a robust content management workflow to broaden the coverage of topics.

Risk prediction with imperfect survival outcome information from electronic health records.

Readily available proxies for the time of disease onset such as the time of the first diagnostic code can lead to substantial risk prediction error if performing analyses based on poor proxies. Due to the lack of detailed documentation and labor intensiveness of manual annotation, it is often only feasible to ascertain for a small subset the current status of the disease by a follow-up time rather than the exact time. In this paper, we aim to develop risk prediction models for the onset time efficiently leveraging both a small number of labels on the current status and a large number of unlabeled observations on imperfect proxies. Under a semiparametric transformation model for onset and a highly flexible measurement error model for proxy onset time, we propose the semisupervised risk prediction method by combining information from proxies and limited labels efficiently. From an initially estimator solely based on the labeled subset, we perform a one-step correction with the full data augmenting against a mean zero rank correlation score derived from the proxies. We establish the consistency and asymptotic normality of the proposed semisupervised estimator and provide a resampling procedure for interval estimation. Simulation studies demonstrate that the proposed estimator performs well in a finite sample. We illustrate the proposed estimator by developing a genetic risk prediction model for obesity using data from Mass General Brigham Healthcare Biobank.

Online Forums as a Tool for Broader Inclusion of Voices on Health Care Communication Experiences and Serious Illness Care: Mixed Methods Study.

BACKGROUND: Existing health care research, including serious illness research, often underrepresents individuals from historically marginalized communities. Capturing the nuanced perspectives of individuals around their health care communication experiences is difficult. New research strategies are needed that increase engagement of individuals from diverse backgrounds. OBJECTIVE: The aim of this study was to develop a mixed methods approach with qualitative online forums to better understand health communication experiences of individuals, including people from groups historically marginalized such as Black and Latino individuals; older adults; and people with low income, disability, or serious illness. METHODS: We used a multiphase mixed methods, community-informed research approach to design study instruments and engage participants. We engaged a diverse group of collaborators with lived experience of navigating the health care system who provided feedback on instruments, added concepts for testing, and offered guidance on creating a safe experience for participants (phase 1). We conducted a national quantitative survey between April and May 2021 across intrapersonal, interpersonal, and systems-level domains, with particular focus on interpersonal communication between patients and clinicians (phase 2). We conducted two asynchronous, qualitative online forums, a technique used in market research, between June and August 2021, which allowed us to contextualize the learnings and test concepts and messages (phase 3). Using online forums allowed us to probe more deeply into results and hypotheses from the survey to better understand the "whys" and "whats" that surfaced and to test public messages to encourage action around health. RESULTS: We engaged 46 community partners, including patients and clinicians from a Federally Qualified Health Center, to inform study instrument design. In the quantitative survey, 1854 adults responded, including 50.5% women, 25.2% individuals over 65 years old, and 51.9% individuals with low income. Nearly two-thirds identified as non-Hispanic white (65.7%), 10.4% identified as non-Hispanic Black, and 15.5% identified as Hispanic/Latino. An additional 580 individuals participated in online forums, including 60.7% women, 17.4% individuals over 65 years old, and 49.0% individuals with low income. Among the participants, 70.3% identified as non-Hispanic white, 16.0% as non-Hispanic Black, and 9.5% as Hispanic/Latino. We received rich, diverse input from our online forum participants, and they highlighted satisfaction and increased knowledge with engagement in the forums. CONCLUSIONS: We achieved modest overrepresentation of people who were over 65 years old, identified as non-Hispanic Black, and had low income in our online forums. The size of the online forums (N=580) reflected the voices of 93 Black and 55 Hispanic/Latino participants. Individuals who identify as Hispanic/Latino remained underrepresented, likely because the online forums were offered only in English. Overall, our findings demonstrate the feasibility of using the online forum qualitative approach in a mixed methods study to contextualize, clarify, and expound on quantitative findings when designing public health and clinical communications interventions.

Reliability and Validity of the East Asia-Pacific Early Child Development Scales: A Longitudinal Validation Study in China.

This study examined the test-retest reliability and predictive validity of the East Asia-Pacific Early Child Development Scales (EAP-ECDS) Short Form. In China, preschools typically provide children with educational activities in age-segregated classrooms - Kindergarten Level 1 (K1) (3 to 4 years), Kindergarten Level 2 (K2) (4 to 5 years), and Kindergarten Level 3 (K3) (5 to 6 years). A total of 709 children in K2 (Mage = 57.85 months, SD = 4.77) were randomly selected from 29 kindergartens in Shanghai municipality and Guizhou province of China. Children were assessed using the EAP-ECDS in K2 and K3. School readiness was assessed in K3, and literacy and mathematics achievement were assessed in Grade 2. Pearson's correlation coefficient and intraclass correlation coefficient (ICC = 0.73) indicated that the tool had good test-retest reliability across K2 and K3. Regarding predictive validity, K2 EAP-ECDS predicted K3 school readiness (ß = 0.26), Grade 2 language and literacy (ß = 0.18) and mathematics (ß = 0.22) after adjusting for age, gender, socioeconomic status, and region. Findings support using the tool to measure the holistic development of preschool-aged children in China and the region.

Paving the way for universal medical student training in serious illness communication: the Massachusetts Medical Schools' Collaborative.

BACKGROUND: Patients with serious illness look to their clinicians for discussion and guidance on high-stakes treatment decisions, which are complex, emotional and value-laden. However, required training in serious illness communication is rare in U.S. medical schools, with efforts at curricular reform stymied by competing institutional demands, lack of resources and accreditation requirements. We describe an approach to building and scaling medical student training in serious illness communication through the creation of a statewide collaborative of medical schools. METHODS: The Massachusetts Medical Schools' Collaborative is a first-of-its-kind group that promotes longitudinal, developmentally-based curricula in serious illness communication for all students. Convened externally by the Massachusetts Coalition for Serious Illness Care, the collaborative includes faculty, staff, and students from four medical schools. RESULTS: The collaborative started with listening to member's perspectives and collectively developed core competencies in serious illness communication for implementation at each school. We share early lessons on the opportunities, challenges and sustainability of our statewide collective action to influence curricular reform, which can be replicated in other topic areas. CONCLUSIONS: Our next steps include curriculum mapping, student focus groups and faculty development to guide successful and enduring implementation of the competencies to impact undergraduate medical education in Massachusetts and beyond.

Publishing fast and slow: A path toward generalizability in psychology and AI.

Artificial intelligence (AI) shares many generalizability challenges with psychology. But the fields publish differently. AI publishes fast, through rapid preprint sharing and conference publications. Psychology publishes more slowly, but creates integrative reviews and meta-analyses. We discuss the complementary advantages of each strategy, and suggest that incorporating both types of strategies could lead to more generalizable research in both fields.

Developing and evaluating risk prediction models with panel current status data.

Panel current status data arise frequently in biomedical studies when the occurrence of a particular clinical condition is only examined at several prescheduled visit times. Existing methods for analyzing current status data have largely focused on regression modeling based on commonly used survival models such as the proportional hazards model and the accelerated failure time model. However, these procedures have the limitations of being difficult to implement and performing sub-optimally in relatively small sample sizes. The performance of these procedures is also unclear under model misspecification. In addition, no methods currently exist to evaluate the prediction performance of estimated risk models with panel current status data. In this paper, we propose a simple estimator under a general class of nonparametric transformation (NPT) models by fitting a logistic regression working model and demonstrate that our proposed estimator is consistent for the NPT model parameter up to a scale multiplier. Furthermore, we propose nonparametric estimators for evaluating the prediction performance of the risk score derived from model fitting, which is valid regardless of the adequacy of the fitted model. Extensive simulation results suggest that our proposed estimators perform well in finite samples and the regression parameter estimators outperform existing estimators under various scenarios. We illustrate the proposed procedures using data from the Framingham Offspring Study.

Changes in Biomarkers of Cigarette Smoke Exposure After 6 Days of Switching Exclusively or Partially to Use of the JUUL System with Two Nicotine Concentrations: A Randomized Controlled Confinement Study in Adult Smokers.

INTRODUCTION: Evidence suggests that cigarette smokers who switch to electronic nicotine delivery systems (ENDS) reduce their exposure to harmful toxicants and carcinogens. It is unclear if dual-use is associated with decreases in exposure to toxicants. METHODS: This parallel-group confinement study assessed changes in biomarkers of exposure (BOEs) over six days among healthy adult smokers who were randomized into 1 of 11 study groups: eight JUUL-brand System (JUUL) groups (4 JUUL flavors [Virginia Tobacco, Menthol, Mint, Mango] × 2 nicotine concentrations [5.0% or 3.0% by weight]); Dual-Use group used preferred JUUL flavor (5.0% nicotine) and ≤50% usual brand (UB) cigarettes/day; UB Cigarette group and one group abstained from all tobacco/nicotine product use (Abstinence group). Urine and blood analysis assessed changes in primary BOE endpoints (NNAL, 3-HPMA, MHBMA, S-PMA COHb) and secondary BOE endpoints (NNN, HMPMA, CEMA, 1-OHP, O-toluidine, 2-NA, 4-ABP) among 279 adult smokers. RESULTS: In JUUL groups, median percent reductions in primary BOEs (Day 6-Baseline) were 90%-≥100% of Abstinence; there were no significant differences between JUUL groups and Abstinence. All reductions in JUUL groups were substantially and statistically significantly greater than reductions in the UB Cigarette group (ps < 0.025). Median reductions in primary BOEs in the Dual-Use group were 43%-55% of Abstinence. Similar results were observed for secondary BOEs. CONCLUSION: This study suggests that the use of JUUL as a complete or partial substitute (i.e., dual-use with ≥50% reduction in cigarette consumption) for combustible cigarettes can substantially reduce exposure to multiple toxins associated with cigarette smoking. IMPLICATIONS: This study adds to the growing body of evidence supporting the utility of ENDS products as potentially reduced-harm alternatives to cigarettes for adult smokers. Adult smokers who switched completely from cigarette smoking to use of the JUUL System ("JUUL") in two nicotine concentrations (5.0% and 3.0%) and four flavors significantly reduced their exposure to multiple classes of cigarette-related toxicants. Additionally, smokers who used JUUL and continued smoking but reduced their daily cigarette consumption by ≥50% (dual users) also significantly reduced their toxicant exposure compared to cigarette smoking.

A Sequential Multiple Assignment Randomized Trial (SMART) study of medication and CBT sequencing in the treatment of pediatric anxiety disorders.

BACKGROUND: Treatment of a child who has an anxiety disorder usually begins with the question of which treatment to start first, medication or psychotherapy. Both have strong empirical support, but few studies have compared their effectiveness head-to-head, and none has investigated what to do if the treatment tried first isn't working well-whether to optimize the treatment already begun or to add the other treatment. METHODS: This is a single-blind Sequential Multiple Assignment Randomized Trial (SMART) of 24 weeks duration with two levels of randomization, one in each of two 12-week stages. In Stage 1, children will be randomized to fluoxetine or Coping Cat Cognitive Behavioral Therapy (CBT). In Stage 2, remitters will continue maintenance-level therapy with the single-modality treatment received in Stage 1. Non-remitters during the first 12 weeks of treatment will be randomized to either [1] optimization of their Stage 1 treatment, or [2] optimization of Stage 1 treatment and addition of the other intervention. After the 24-week trial, we will follow participants during open, naturalistic treatment to assess the durability of study treatment effects. Patients, 8-17 years of age who are diagnosed with an anxiety disorder, will be recruited and treated within 9 large clinical sites throughout greater Los Angeles. They will be predominantly underserved, ethnic minorities. The primary outcome measure will be the self-report score on the 41-item youth SCARED (Screen for Child Anxiety Related Disorders). An intent-to-treat analysis will compare youth randomized to fluoxetine first versus those randomized to CBT first ("Main Effect 1"). Then, among Stage 1 non-remitters, we will compare non-remitters randomized to optimization of their Stage 1 monotherapy versus non-remitters randomized to combination treatment ("Main Effect 2"). The interaction of these main effects will assess whether one of the 4 treatment sequences (CBT➔CBT; CBT➔med; med➔med; med➔CBT) in non-remitters is significantly better or worse than predicted from main effects alone. DISCUSSION: Findings from this SMART study will identify treatment sequences that optimize outcomes in ethnically diverse pediatric patients from underserved low- and middle-income households who have anxiety disorders. TRIAL REGISTRATION: This protocol, version 1.0, was registered in ClinicalTrials.gov on February 17, 2021 with Identifier: NCT04760275 .

Prescribing Isotretinoin for Transgender Patients: A Call to Action and Recommendations.

Case Scenerio: A 26-year-old patient presents to the dermatology clinic with severe nodulocystic scarring acne. The patient identifies as a transgender male and notes that he has been receiving hormone replacement therapy for the past 4 years with weekly intramuscular testosterone injections.

Standardized Postpartum Follow-Up for Women with Pregnancy Complications: Barriers to Access and Perceptions of Maternal Cardiovascular Risk.

OBJECTIVE: Certain obstetrical complications are known to increase a woman's risk of future cardiovascular disease (CVD). The Maternal Health Clinic (MHC) provides postpartum cardiovascular risk counselling and follow-up; however, half of women referred do not attend. This study aimed to identify barriers to access, as well as whether attendance at the MHC improved the accuracy of patients' CVD risk perception. METHODS: MHC patients completed a CVD risk perception questionnaire prior to being assessed and 3 months after their appointment ("attendees"). Calculated lifetime CVD risk scores were compared with perceived risk to assess accuracy of risk perception. Patients who did not attend their MHC appointment ("non-attendees") were administered the questionnaire by phone and asked about perceived barriers to access. RESULTS: Sixty-seven of 137 eligible attendees (48.9%) completed both the pre- and post-MHC questionnaires. Significantly more participants accurately estimated their absolute CVD risk after their MHC appointment, although the majority continued to underestimate their risk. Among non-attendees, 81 of 130 women (62.3%) completed the questionnaire. The most common barriers to access cited were being too busy with childcare, accessing follow-up with the patient's family doctor instead, and difficulty attending their appointment. CONCLUSION: Lack of time and inconvenience were two common barriers to accessing the MHC. Improved collaboration with primary care providers and use of telemedicine may help to mitigate these issues. Both attendees and non-attendees appeared to have an inadequate perception of CVD risk. Standardized postpartum CVD risk screening and counselling may be an effective method of providing these women with risk education and improving the accuracy of their risk perception.

Patient-Reported Pain in Patients with Breast Cancer Who Receive Radiotherapy.

BACKGROUND: Patients who receive radiation treatment (RT) for breast cancer often report pain, which contributes negatively to quality of life (QoL). AIMS: To identify demographic, treatment, and disease characteristics associated with pain and changes in pain before and after RT using the Edmonton Symptom Assessment Scale (ESAS). DESIGN: Retrospective study. SETTINGS: Odette Cancer Centre. PARTICIPANTS: Patients diagnosed with nonmetastatic breast cancer from January 2011-June 2017 with at least one ESAS completed pre-RT and one completed post-RT. METHODS: Data on systemic treatment, radiation, patient demographics, and disease stage were extracted. To identify factors associated with pain before and after RT and changes in pain, univariate and multivariate general linear regression analysis were conducted. p < .05 was considered statistically significant. RESULTS: This study included 1,222 female patients with a mean age of 59 years. ESAS was completed an average of 28 days before RT (baseline) and 142 days after RT, respectively. In multivariable analysis, higher baseline pain scores were associated with having recently completed adjuvant chemotherapy (p = .002) and eventual receipt of locoregional (p = .026) or chest wall (p = .003) radiation. Adjuvant chemotherapy (p = .002) and chest wall radiation (p = .03), were associated with a significant reduction in pain score after radiotherapy, while locoregional RT was associated with a higher pain score after RT (p < .001). CONCLUSIONS: Patients with locoregional RT had higher baseline pain that remained elevated after RT completion and should be screened for pain and provided with pain management and support when necessary.

The use of Goeckerman therapy in managing erythrodermic psoriasis resistant to multiple medications.

Erythrodermic psoriasis is a relatively rare, more dangerous inflammatory variant of psoriasis associated with high morbidity and mortality. It can be exceptionally challenging to manage, defeating even the most experienced dermatologist's arsenal of treatment strategies. Goeckerman therapy, a regimen of ultraviolet B phototherapy and crude coal tar, has demonstrable efficacy in severe and recalcitrant plaque-type psoriasis. However, its utility in erythrodermic psoriasis has not been explored within the dermatology literature. Herein, we present a patient with a long-standing history of erythrodermic psoriasis refractory to eleven treatment modalities including four biologic agents, who had his erythroderma 'turned around' following Goeckerman therapy. 'Turned around' is used to describe dramatically reducing a patient's cutaneous inflammation so that previously recalcitrant disease can now respond to maintenance therapy. The importance of a one to three week 'cool down' period of topical corticosteroid therapy prior to phototherapy or crude coal tar use is highlighted in this case as well. Although Goeckerman therapy is no longer regularly used, it remains one of the most efficacious treatments available for intractable psoriasis, attracting patients from all over the country desperate for symptom relief. This case suggests it may be useful in 'turning around' extremely difficult-to-treat erythrodermic psoriasis as well.

Pre-exposure prophylaxis for preventing acquisition of HIV: A cross-sectional study of patients, prescribers, uptake, and spending in the United States, 2015-2016.

BACKGROUND: In 2015, there were approximately 40,000 new HIV diagnoses in the United States. Pre-exposure prophylaxis (PrEP) is an effective strategy that reduces the risk of HIV acquisition; however, uptake among those who can benefit from it has lagged. In this study, we 1) compared the characteristics of patients who were prescribed PrEP with individuals newly diagnosed with HIV infection, 2) identified the specialties of practitioners prescribing PrEP, 3) identified metropolitan statistical areas (MSAs) within the US where there is relatively low uptake of PrEP, and 4) reported median amounts paid by patients and third-party payors for PrEP. METHODS AND FINDINGS: We analyzed prescription drug claims for individuals prescribed PrEP in the Integrated Dataverse (IDV) from Symphony Health for the period of September 2015 to August 2016 to describe PrEP patients, prescribers, relative uptake, and payment methods in the US. Data were available for 75,839 individuals prescribed PrEP, and findings were extrapolated to approximately 101,000 individuals, which is less than 10% of the 1.1 million adults for whom PrEP was indicated. Compared to individuals with newly diagnosed HIV infection, PrEP patients were more likely to be non-Hispanic white (45% versus 26.2%), older (25% versus 19% at ages 35-44), male (94% versus 81%), and not reside in the South (30% versus 52% reside in the South).Using a ratio of the number of PrEP patients within an MSA to the number of newly diagnosed individuals with HIV infection, we found MSAs with relatively low uptake of PrEP were concentrated in the South. Of the approximately 24,000 providers who prescribed PrEP, two-thirds reported primary care as their specialty. Compared to the types of payment methods that people living with diagnosed HIV (PLWH) used to pay for their antiretroviral treatment in 2015 to 2016 reported in the Centers for Disease Control and Prevention (CDC) HIV Surveillance Special Report, PrEP patients were more likely to have used commercial health insurance (80% versus 35%) and less likely to have used public healthcare coverage or a publicly sponsored assistance program to pay for PrEP (12% versus 45% for Medicaid). Third-party payors covered 95% of the costs of PrEP. Overall, we estimated the median annual per patient out-of-pocket spending on PrEP was approximately US$72. Limitations of this study include missing information on prescription claims of patients not included in the database, and for those included, some patients were missing information on patient diagnosis, race/ethnicity, educational attainment, and income (34%-36%). CONCLUSIONS: Our findings indicate that in 2015-2016, many individuals in the US who could benefit from being on PrEP were not receiving this HIV prevention medication, and those prescribed PrEP had a significantly different distribution of characteristics from the broader population that is at risk for acquiring HIV. PrEP patients were more likely to pay for PrEP using commercial or private insurance, whereas PLWH were more likely to pay for their antiretroviral treatment using publicly sponsored programs. Addressing the affordability of PrEP and otherwise promoting its use among those with indications for PrEP represents an important opportunity to help end the HIV epidemic.

Symptom correlates of dyspnea in advanced cancer patients using the Edmonton Symptom Assessment System.

PURPOSE: Dyspnea is frequently experienced in advanced cancer patients and is associated with poor prognosis and functional decline. This study used the Edmonton Symptom Assessment System (ESAS) to characterize the relationship between dyspnea and concurrent symptoms experienced by advanced cancer patients. METHODS: A prospective database was collected and analyzed to extract patient demographics and ESAS scores. Logistic regression analysis and generalized estimating equations (GEE) identified correlations of other ESAS symptoms in three categories: severity of dyspnea (none, mild, moderate, severe), moderate/severe dyspnea (ESAS ≥ 4), and presence of dyspnea (ESAS ≥ 1), at patients' first visit and over time, respectively. RESULTS: Multivariable analysis revealed drowsiness (p = 0.001), and anxiety (p = 0.01) and appetite loss (p = 0.02) were associated with increased severity of dyspnea at first visit. Over time, tiredness (p = 0.02), drowsiness (p = 0.04), nausea (p = 0.02), and anxiety (p = 0.0006) were more likely to experience increased dyspnea severity. Tiredness (p = 0.0003), depression (p = 0.03), and appetite loss (p = 0.003) were significant for moderate/severe dyspnea at first visit. Over multiple visits, tiredness (p < 0.0001), anxiety (p = 0.0008), and appetite loss (p = 0.0008) had higher probabilities of moderate/severe dyspnea. For the presence of dyspnea at the first visit, anxiety (p = 0.03) and drowsiness (p = 0.002) were significantly correlated with an increased frequency of dyspnea. Over time, anxiety (p < 0.0001) and drowsiness (p < 0.0001) remained significant with the addition of nausea (p = 0.0007). CONCLUSIONS: The highly interactive relationship between dyspnea and other common cancer symptoms necessitates the development of comprehensive symptom assessments and utilization of multimodal management approaches that consider concurrent symptoms for improved identification and treatment of dyspnea.

Psychological morbidity in women diagnosed with ductal carcinoma in situ compared with women with early breast cancer receiving radiotherapy.

PURPOSE: Despite having an excellent prognosis, patients with ductal carcinoma in situ (DCIS) report significant anxiety and depression following diagnosis. This study evaluated psychological morbidity using the Edmonton Symptom Assessment Scale (ESAS) in patients with DCIS compared with women with early-stage invasive breast cancer (EIBC) receiving radiotherapy (RT). METHODS: We identified patients diagnosed with DCIS or EIBC (stage I or II breast cancer) from 2011 to 2017 who had at least one ESAS completed pre- and post-RT. Data on systemic treatment, radiation, patient demographics, and disease stage were extracted from existing databases. Psychological morbidity was evaluated through measurement of depression, anxiety, and overall wellbeing within the ESAS. The Wilcoxon rank-sum test or chi-square test was performed for continuous or categorical variables. RESULTS: This study included 137 women with DCIS and 963 women with EIBC. ESAS was completed on average 28 days before RT (baseline) and 142 days after RT. Baseline ESAS scores showed significantly higher rates of depression among women with EIBC compared with those with DCIS (p = 0.006). Patients with EIBC also reported higher levels of anxiety and lower overall wellbeing than patients with DCIS, but this difference was not statistically significant. Post-RT ESAS scores showed significantly higher anxiety in patients with EIBC compared with DCIS (p = 0.049). Post-RT measures of anxiety and overall wellbeing were higher in patients with EIBC but differences were not statistically significant. CONCLUSION: Women with DCIS experience relatively less psychological morbidity than women with EIBC, pre- and post-RT.