Impact of Telemedicine on Access to Care for Rural Transgender and Gender-Diverse Youth.

OBJECTIVE: To explore the impact of telemedicine on access to gender-affirming care for rural transgender and gender diverse youth. STUDY DESIGN: A retrospective analysis of data drawn from the electronic medical records of a clinic that provides approximately 10 000 adolescent and young adult visits per year and serves patients seeking gender health care. The no-show rate was examined as a proxy for access to care due to anticipated challenges with recruiting a representative sample of a historically marginalized population. Logistic regression with generalized estimating equations was conducted to model the association between the odds of a no-show visit and covariates of interest. RESULTS: Telemedicine visits, rural home address, gender health visits, longer travel time, and being younger than 18 years old were associated with lower odds of a no-show in univariate models (n = 17 928 visits). In the adjusted model, the OR of no-shows for gender health visits was 0.56 (95% CI 0.42-0.74), adjusting for rurality, telemedicine, age (< or >18 years), and travel time to the clinic. CONCLUSIONS: In this study, telemedicine was associated with reduced no-shows overall, and especially for rural, transgender and gender diverse youth, and patients who hold both identities. Although the no-show rate does not fully capture barriers to access, these findings provide insight into how this vulnerable population may benefit from expanded access to telemedicine for rural individuals whose communities may lack providers with the skills to serve this population.

Heart rate patterns predicting cerebral palsy in preterm infants.

BACKGROUND: Heart rate (HR) patterns can inform on central nervous system dysfunction. We previously used highly comparative time series analysis (HCTSA) to identify HR patterns predicting mortality among patients in the neonatal intensive care unit (NICU) and now use this methodology to discover patterns predicting cerebral palsy (CP) in preterm infants. METHOD: We studied NICU patients <37 weeks' gestation with archived every-2-s HR data throughout the NICU stay and with or without later diagnosis of CP (n = 57 CP and 1119 no CP). We performed HCTSA of >2000 HR metrics and identified 24 metrics analyzed on HR data from two 7-day periods: week 1 and 37 weeks' postmenstrual age (week 1, week 37). Multivariate modeling was used to optimize a parsimonious prediction model. RESULTS: Week 1 HR metrics with maximum AUC for CP prediction reflected low variability, including "RobustSD" (AUC 0.826; 0.772-0.870). At week 37, high values of a novel HR metric, "LongSD3," the cubed value of the difference in HR values 100 s apart, were added to week 1 HR metrics for CP prediction. A combined birthweight + early and late HR model had AUC 0.853 (0.805-0.892). CONCLUSIONS: Using HCTSA, we discovered novel HR metrics and created a parsimonious model for CP prediction in preterm NICU patients. IMPACT: We discovered new heart rate characteristics predicting CP in preterm infants. Using every-2-s HR from two 7-day periods and highly comparative time series analysis, we found a measure of low variability HR week 1 after birth and a pattern of recurrent acceleration in HR at term corrected age that predicted CP. Combined clinical and early and late HR features had AUC 0.853 for CP prediction.

Intimate partner violence during the perinatal period by disability status: Findings from a United States population-based analysis.

AIMS: The aim of the current study was to compare the prevalence of intimate partner violence (IPV) during the perinatal period among respondents with self-reported disability compared with those without a disability. DESIGN: We conducted a secondary analysis of nationally representative data from the Pregnancy Risk Assessment Monitoring System data from 24 participating United States between 2018 and 2020. METHODS: A cross-sectional sample of 43,837 respondents provided data on disability, including difficulty in vision, hearing, ambulation, cognition, communication and self-care. The exposure was perinatal IPV, defined as experiencing abuse by a current or ex-partner in the year before or during pregnancy. Regression models were used to calculated odds of IPV by disability status while accounting for relevant sociodemographic characteristics. RESULTS: Respondents who self-reported disabilities experienced IPV at a higher rate than those without disabilities, both before and during pregnancy. In fully adjusted models, respondents with disabilities had about 2.6 times the odds of experiencing IPV before pregnancy, and about 2.5 times the odds of experiencing IPV during pregnancy, compared with those without disabilities. CONCLUSION: Respondents with disabilities experienced IPV at higher rates than the general population, and thus are at increased risk for adverse maternal, neonatal and infant health outcomes. IMPACT: Perinatal IPV is a significant issue globally, and our findings suggest perinatal IPV is particularly salient for persons with disability. Findings highlight the need to screen women with disabilities for IPV during the perinatal period as well as the importance of providing them appropriate, accessible information, resources and referrals.

Depressive symptoms during the perinatal period by disability status: Findings from the United States Pregnancy Risk Assessment Monitoring System.

AIMS: The aim of the current study was to compare the prevalence of depressive symptoms during the perinatal period among respondents with a disability as compared to those without a disability. DESIGN: We conducted a secondary analysis of nationally representative data from the Pregnancy Risk Assessment Monitoring System data from 24 participating United States between 2018 and 2020. METHODS: A cross-sectional sample of 37,989 respondents provided data on disability, including difficulty in vision, hearing, ambulation, cognition, communication and self-care. The outcome of interest was perinatal depressive symptoms, defined as experiencing depressive symptoms during the antenatal period or postpartum period. Regression models were used to calculate odds of depressive symptoms during these two time periods by disability status while controlling for relevant sociodemographic characteristics and depressive symptoms prior to pregnancy. RESULTS: Respondents with disabilities experienced a higher prevalence of depressive symptoms in both the antenatal period and postpartum period as compared to those without disabilities. In fully adjusted models, respondents with disabilities had 2.4 times the odds of experiencing depressive symptoms during pregnancy and 2.1 times the odds of experiencing postpartum depressive symptoms as compared to respondents without disabilities. CONCLUSION: Respondents with disabilities experience a higher prevalence of depressive symptoms throughout the perinatal period thereby increasing the risk for adverse maternal, neonatal and infant health outcomes. IMPACT: Perinatal depression is a significant public health issue globally, and our findings suggest that persons with disability are at an increased risk for depressive symptoms both during pregnancy and in the postpartum period. Our findings represent a call to action to improve clinical and supportive services for women with disabilities during the perinatal period to improve their mental health and the consequent health of their offspring. PATIENT OR PUBLIC CONTRIBUTION: We thank our Community Advisory Board members who have been instrumental in the conception of this study.

Statewide Analysis Reveals Period of Well-Child Visit Attendance for Earlier Diagnosis of Autism Spectrum Disorder.

OBJECTIVE: To explore the relationship between well-child visit (WCV) attendance during early childhood and age at autism spectrum disorder (ASD) diagnosis using data drawn from a statewide all-payer claims database. STUDY DESIGN: We used a correlational study design with longitudinal data drawn from the Virginia All-Payer Claims Database. All children born in 2011 with a diagnosis of ASD were included (n = 253). Survival analysis determined the impact of WCV attendance on ASD diagnosis at each American Academy of Pediatrics-recommended early childhood visit, and the 5-year visit. RESULTS: Survival analysis revealed a significant impact of WCV attendance at the 24-month, 3-, and 4-year visits on earlier ASD diagnosis. Children who attended the 24-month visit were diagnosed nearly 10 months earlier than those who did not. Overall, children with ASD attended fewer than 50% of visits during early childhood. CONCLUSIONS: Promoting consistent WCV attendance during early childhood is an actionable strategy for improving early identification of ASD. Further exploration is needed to determine barriers to visit attendance and the impact of patterns of early childhood WCV attendance on age of ASD diagnosis. Development and implementation of interventions to promote adherence to the American Academy of Pediatrics-recommended visits is needed.

Attempts to conceive and the COVID-19 pandemic: data from the Apple Women's Health Study.

BACKGROUND: Previous studies have suggested that emergent events may affect pregnancy planning decisions. However, few have investigated the effect of factors related to the COVID-19 pandemic on pregnancy planning, measured by attempting conception, and how attempting conception status may differ by individual-level factors, such as social status or educational level. OBJECTIVE: This study aimed to examine the effects of factors related to the COVID-19 pandemic, until March 2021, on attempting conception status and to assess the effect measure modification by educational level and subjective social status. STUDY DESIGN: We conducted a longitudinal analysis within a subgroup of 21,616 participants in the Apple Women's Health Study who enrolled from November 2019 to March 2021, who met the inclusion criteria, and who responded to the monthly status menstrual update question on attempting conception status (yes or no). Participants reporting hysterectomy, pregnancy, lactation, or menopause were excluded. We used generalized estimating equation methodology to fit logistic regression models that estimate odds ratios and 95% confidence intervals for the association between the proportion of participants attempting conception and the month of response (compared with a prepandemic reference month of February 2020) while accounting for longitudinal correlation and adjusting for age, race and ethnicity, and marital status. We stratified the analysis by social status and educational level. RESULTS: We observed a trend of reduced odds of attempting conception, with an 18% reduction in the odds of attempting conception in August 2020 and October 2020 compared with the prepandemic month of February 2020 (August odds ratio: 0.82 [95% confidence interval, 0.70-0.97]; October odds ratio: 0.82 [95% confidence interval, 0.69-0.97). The participants with lower educational level (no college education) experienced a sustained reduction in the odds of attempting to conceive from June 2020 to March 2021 compared with February 2020, with up to a 24% reduction in the odds of attempting to conceive in October 2020 (odds ratio, 0.76; 95% confidence interval, 0.59-0.96). Among participants that were college educated, we observed an initial reduction in the odds of attempting to conceive starting in July 2020 (odds ratio 0.73; 95% confidence interval, 0.54-0.99) that returned near prepandemic odds. Moreover, we observed a reduction in the odds of attempting to conceive among those with low subjective social status, with a decline in the odds of attempting to conceive beginning in July 2020 (odds ratio, 0.83; 95% confidence interval, 0.63-1.10) and continuing until March 2021 (odds ratio, 0.79; 95% confidence interval, 0.59-1.06), with the greatest reduction in odds in October 2020 (odds ratio, 0.67; 95% confidence interval, 0.50-0.91). CONCLUSION: Among women in the Apple Women's Health Study cohort, our findings suggested a reduction in the odds of attempting to conceive during the COVID-19 pandemic, until March 2021, particularly among women of lower educational level and lower perceived social status.

Design and methods of the Apple Women's Health Study: a digital longitudinal cohort study.

BACKGROUND: Prospective longitudinal cohorts assessing women's health and gynecologic conditions have historically been limited. OBJECTIVE: The Apple Women's Health Study was designed to gain a deeper understanding of the relationship among menstrual cycles, health, and behavior. This paper describes the design and methods of the ongoing Apple Women's Health Study and provides the demographic characteristics of the first 10,000 participants. STUDY DESIGN: This was a mobile-application-based longitudinal cohort study involving survey and sensor-based data. We collected the data from 10,000 participants who responded to the demographics survey on enrollment between November 14, 2019 and May 20, 2020. The participants were asked to complete a monthly follow-up through November 2020. The eligibility included installed Apple Research app on their iPhone with iOS version 13.2 or later, were living in the United States, being of age greater than 18 years (19 in Alabama and Nebraska, 21 years old in Puerto Rico), were comfortable in communicating in written and spoken English, were the sole user of an iCloud account or iPhone, and were willing to provide consent to participate in the study. RESULTS: The mean age at enrollment was 33.6 years old (±standard deviation, 10.3). The race and ethnicity was representative of the US population (69% White and Non-Hispanic [6910/10,000]), whereas 51% (5089/10,000) had a college education or above. The participant geographic distribution included all the US states and Puerto Rico. Seventy-two percent (7223/10,000) reported the use of an Apple Watch, and 24.4% (2438/10,000) consented to sensor-based data collection. For this cohort, 38% (3490/9238) did not respond to the Monthly Survey: Menstrual Update after enrollment. At the 6-month follow-up, there was a 35% (3099/8972) response rate to the Monthly Survey: Menstrual Update. 82.7% (8266/10,000) of the initial cohort and 95.1% (2948/3099) of the participants who responded to month 6 of the Monthly Survey: Menstrual Update tracked at least 1 menstrual cycle via HealthKit. The participants tracked their menstrual bleeding days for an average of 4.44 (25%-75%; range, 3-6) calendar months during the study period. Non-White participants were slightly more likely to drop out than White participants; those remaining at 6 months were otherwise similar in demographic characteristics to the original enrollment group. CONCLUSION: The first 10,000 participants of the Apple Women's Health Study were recruited via the Research app and were diverse in race and ethnicity, educational attainment, and economic status, despite all using an Apple iPhone. Future studies within this cohort incorporating this high-dimensional data may facilitate discovery in women's health in exposure outcome relationships and population-level trends among iPhone users. Retention efforts centered around education, communication, and engagement will be utilized to improve the survey response rates, such as the study update feature.

Heart Rate and Pulse Oximetry Dynamics in the First Week after Birth in Neonatal Intensive Care Unit Patients and the Risk of Cerebral Palsy.

OBJECTIVE: Infants in the neonatal intensive care unit (NICU) are at high risk of adverse neuromotor outcomes. Atypical patterns of heart rate (HR) and pulse oximetry (SpO2) may serve as biomarkers for risk assessment for cerebral palsy (CP). The purpose of this study was to determine whether atypical HR and SpO2 patterns in NICU patients add to clinical variables predicting later diagnosis of CP. STUDY DESIGN: This was a retrospective study including patients admitted to a level IV NICU from 2009 to 2017 with archived cardiorespiratory data in the first 7 days from birth to follow-up at >2 years of age. The mean, standard deviation (SD), skewness, kurtosis and cross-correlation of HR and SpO2 were calculated. Three predictive models were developed using least absolute shrinkage and selection operator regression (clinical, cardiorespiratory and combined model), and their performance for predicting CP was evaluated. RESULTS: Seventy infants with CP and 1,733 controls met inclusion criteria for a 3.8% population prevalence. Area under the receiver operating characteristic curve for CP prediction was 0.7524 for the clinical model, 0.7419 for the vital sign model, and 0.7725 for the combined model. Variables included in the combined model were lower maternal age, outborn delivery, lower 5-minute Apgar's score, lower SD of HR, and more negative skewness of HR. CONCLUSION: In this study including NICU patients of all gestational ages, HR but not SpO2 patterns added to clinical variables to predict the eventual diagnosis of CP. Identification of risk of CP within the first few days of life could result in improved therapy resource allocation and risk stratification in clinical trials of new therapeutics. KEY POINTS: · SD and skewness of HR have some added predictive value of later diagnosis of CP.. · SpO2 measures do not add to CP prediction.. · Combining clinical variables with early HR measures may improve the prediction of later CP..

Anesthesiologist Age and Sex Influence Patient Perceptions of Physician Competence.

BACKGROUND: Uncovering patients' biases toward characteristics of anesthesiologists may inform ways to improve the patient-anesthesiologist relationship. The authors previously demonstrated that patients prefer anesthesiologists displaying confident body language, but did not detect a sex bias. The effect of anesthesiologists' age on patient perceptions has not been studied. In this follow-up study, it was hypothesized that patients would prefer older-appearing anesthesiologists over younger-appearing anesthesiologists and male over female anesthesiologists. METHODS: Three hundred adult, English-speaking patients were recruited in the Preanesthesia Evaluation and Testing Center. Patients were randomized (150 per group) to view a set of four videos in random order. Each 90-s video featured an older female, older male, younger female, or younger male anesthesiologist reciting the same script describing general anesthesia. Patients ranked each anesthesiologist on confidence, intelligence, and likelihood of choosing the anesthesiologist to care for their family member. Patients also chose the one anesthesiologist who seemed most like a leader. RESULTS: Three hundred patients watched the videos and completed the questionnaire. Among patients younger than age 65 yr, the older anesthesiologists had greater odds of being ranked more confident (odds ratio, 1.92; 95% CI, 1.41 to 2.64; P < 0.001) and more intelligent (odds ratio, 2.24; 95% CI, 1.62 to 3.11; P < 0.001), and had greater odds of being considered a leader (odds ratio, 2.62; 95% CI, 1.72 to 4.00; P < 0.001) when compared with younger anesthesiologists. The preference for older anesthesiologists was not observed in patients age 65 and older. Female anesthesiologists had greater odds of being ranked more confident (odds ratio, 1.46; 95% CI, 1.13 to 1.87; P = 0.003) and more likely to be chosen to care for one's family member (odds ratio, 1.80; 95% CI, 1.40 to 2.31; P < 0.001) compared with male anesthesiologists. The ranking preference for female anesthesiologists on these two measures was observed among white patients and not among nonwhite patients. CONCLUSIONS: Patients preferred older anesthesiologists on the measures of confidence, intelligence, and leadership. Patients also preferred female anesthesiologists on the measures of confidence and likelihood of choosing the anesthesiologist to care for one's family member.

Developing the Total Health Profile, a Generalizable Unified Set of Multimorbidity Risk Scores Derived From Machine Learning for Broad Patient Populations: Retrospective Cohort Study.

BACKGROUND: Multimorbidity clinical risk scores allow clinicians to quickly assess their patients' health for decision making, often for recommendation to care management programs. However, these scores are limited by several issues: existing multimorbidity scores (1) are generally limited to one data group (eg, diagnoses, labs) and may be missing vital information, (2) are usually limited to specific demographic groups (eg, age), and (3) do not formally provide any granularity in the form of more nuanced multimorbidity risk scores to direct clinician attention. OBJECTIVE: Using diagnosis, lab, prescription, procedure, and demographic data from electronic health records (EHRs), we developed a physiologically diverse and generalizable set of multimorbidity risk scores. METHODS: Using EHR data from a nationwide cohort of patients, we developed the total health profile, a set of six integrated risk scores reflecting five distinct organ systems and overall health. We selected the occurrence of an inpatient hospital visitation over a 2-year follow-up window, attributable to specific organ systems, as our risk endpoint. Using a physician-curated set of features, we trained six machine learning models on 794,294 patients to predict the calibrated probability of the aforementioned endpoint, producing risk scores for heart, lung, neuro, kidney, and digestive functions and a sixth score for combined risk. We evaluated the scores using a held-out test cohort of 198,574 patients. RESULTS: Study patients closely matched national census averages, with a median age of 41 years, a median income of $66,829, and racial averages by zip code of 73.8% White, 5.9% Asian, and 11.9% African American. All models were well calibrated and demonstrated strong performance with areas under the receiver operating curve (AUROCs) of 0.83 for the total health score (THS), 0.89 for heart, 0.86 for lung, 0.84 for neuro, 0.90 for kidney, and 0.83 for digestive functions. There was consistent performance of this scoring system across sexes, diverse patient ages, and zip code income levels. Each model learned to generate predictions by focusing on appropriate clinically relevant patient features, such as heart-related hospitalizations and chronic hypertension diagnosis for the heart model. The THS outperformed the other commonly used multimorbidity scoring systems, specifically the Charlson Comorbidity Index (CCI) and the Elixhauser Comorbidity Index (ECI) overall (AUROCs: THS=0.823, CCI=0.735, ECI=0.649) as well as for every age, sex, and income bracket. Performance improvements were most pronounced for middle-aged and lower-income subgroups. Ablation tests using only diagnosis, prescription, social determinants of health, and lab feature groups, while retaining procedure-related features, showed that the combination of feature groups has the best predictive performance, though only marginally better than the diagnosis-only model on at-risk groups. CONCLUSIONS: Massive retrospective EHR data sets have made it possible to use machine learning to build practical multimorbidity risk scores that are highly predictive, personalizable, intuitive to explain, and generalizable across diverse patient populations.

Rural Disparities in Early Childhood Well Child Visit Attendance.

PURPOSE: Children should attend well child visits (WCVs) during early childhood so that developmental disorders may be identified as early as possible, so treatment can begin. The aim of this research was to determine if rurality impacts access to WCV during early childhood, and if altering rurality measurement methods impacts outcomes. DESIGN AND METHODS: We utilized a longitudinal correlational design with early childhood data gathered from the Virginia All Payer Claims Database, which contains claims data from Medicaid and the majority of Virginia commercial insurance payers (n = 6349). WCV attendance was evaluated against three rurality metrics: a traditional metric using Rural-Urban Commuting Area codes, a developed land variable, and a distance to care variable, at a zip code level. RESULTS: Two of the rurality methods revealed that rural children attend fewer WCVs than their urban counterparts, (67% vs. 50% respectively, using a traditional metric; and a 0.035 increase in WCV attendance for every percent increase in developed land). Differences were attenuated by insurance payer; children with Medicaid attend fewer WCVs than those with private insurance. CONCLUSIONS: Young children in rural Virginia attend fewer WCVs than their non-rural counterparts, placing them at higher risk for missing timely developmental disorder screenings. The coronavirus disease pandemic has been associated with an abrupt and significant reduction in vaccination rates, which likely indicates fewer WCVs and concomitant developmental screenings. Pediatric nurses should encourage families of young children to develop a plan for continued WCVs, so that early identification of developmental disorders can be achieved.

Simplified molecular classification of lung adenocarcinomas based on EGFR, KRAS, and TP53 mutations.

BACKGROUND: Gene expression profiling has consistently identified three molecular subtypes of lung adenocarcinoma that have prognostic implications. To facilitate stratification of patients with this disease into similar molecular subtypes, we developed and validated a simple, mutually exclusive classification. METHODS: Mutational status of EGFR, KRAS, and TP53 was used to define seven mutually exclusive molecular subtypes. A development cohort of 283 cytology specimens of lung adenocarcinoma was used to evaluate the associations between the proposed classification and clinicopathologic variables including demographic characteristics, smoking history, fluorescence in situ hybridization and molecular results. For validation and prognostic assessment, 63 of the 283 cytology specimens with available survival data were combined with a separate cohort of 428 surgical pathology specimens of lung adenocarcinoma. RESULTS: The proposed classification yielded significant associations between these molecular subtypes and clinical and prognostic features. We found better overall survival in patients who underwent surgery and had tumors enriched for EGFR mutations. Worse overall survival was associated with older age, stage IV disease, and tumors with co-mutations in KRAS and TP53. Interestingly, neither chemotherapy nor radiation therapy showed benefit to overall survival. CONCLUSIONS: The mutational status of EGFR, KRAS, and TP53 can be used to easily classify lung adenocarcinoma patients into seven subtypes that show a relationship with prognosis, especially in patients who underwent surgery, and these subtypes are similar to classifications based on more complex genomic methods reported previously.

Electrocardiographic left atrial abnormality in patients presenting with ischemic stroke.

BACKGROUND: P wave indices represent electrocardiographic marker of left atrial pathology. We hypothesized that P wave would be more abnormal in patients presenting with ischemic stroke than a comparable group without ischemic stroke. METHODS: We compared P wave terminal force in V1 (PTFV1) between patients admitted with ischemic stroke (case) and patients followed in cardiology clinic (control) at a single medical center. Using logistic regression models, we tested for an association between abnormal PTFV1 (> 4000 µV ms) and ischemic stroke. We also defined several optimal cut-off values of PTFV1 using a LOESS plot and estimated odds ratio of ischemic stroke when moving from one cut-point level to the next higher-level. RESULTS: A total of 297 patients (case 147, control 150) were included. PTFV1 was higher in patients with vs. those without ischemic stroke (median 4620 vs 3994 µV ms; p=0.006). PTFV1 was similar between cardioembolic/cryptogenic and other stroke subtypes. In multivariable analyses adjusting for sex, obesity, age, and hypertension, the association between abnormal PTFV1 and ischemic stroke ceased to be significant (OR 1.53 [0.95, 2.50], p=0.083). Increase to the next cutoff level of PTFV1 (900, 2000, 3000, 4000, 5000, and 6000 µV ms) was associated with 18% increase in odds of having ischemic stroke (vs. no ischemic stroke) (OR 1.18 [1.02, 1.36], p=0.026). CONCLUSION: Patients presenting with acute ischemic stroke are more likely to have abnormal PTFV1. These findings from a real-world clinical setting support the results of cohort studies that left atrial pathology manifested as abnormal PTFV1 is associated with ischemic stroke.

Influence of Sex and Body Language on Patient Perceptions of Anesthesiologists.

BACKGROUND: Patient perception of physician competence is important. The role of body language and physician sex on patient perceptions has not been investigated. The authors hypothesized that patients perceive anesthesiologists displaying confident body language as more competent and that patients would prefer male anesthesiologists. METHODS: Two hundred adult patients presenting to the Preanesthesia Evaluation and Testing Center at the University of Virginia Health System were recruited to participate using consecutive sampling. Patients viewed four 90-s videos in random order. Each video featured a male or female actor displaying confident, high-power poses or unconfident, low-power poses. Each actor recited the same script describing general anesthesia. Patients were randomized (100 per group) to view one of two sets of videos to account for any actor preferences. Participants ranked each actor anesthesiologist on perceived confidence, intelligence, and likelihood of choosing that anesthesiologist to care for their family member. Participants also chose the one actor anesthesiologist who seemed most like a leader. RESULTS: Two hundred patients watched the videos and completed the questionnaire. Actor anesthesiologists displaying confident, high-power body language had greater odds of being ranked as more confident (odds ratio, 2.27; 95% CI, 1.76 to 2.92; P < 0.0001), more intelligent (odds ratio, 1.69; 95% CI, 1.13 to 2.18; P < 0.0001), more likely chosen to care for one's family member (odds ratio, 2.34; 95% CI, 1.82 to 3.02; P < 0.0001), and more likely to be considered a leader (odds ratio, 2.60; 95% CI, 1.86 to 3.65; P < 0.0001). Actor anesthesiologist sex was not associated with ranking for any response measures. CONCLUSIONS: Patients perceive anesthesiologists displaying confident body language as more confident, more intelligent, more like a leader, and are more likely to choose that anesthesiologist to care for their family member. Differences in patient perceptions based on sex of the anesthesiologist were not detected.

Generative retrieval results in positive academic emotions and long-term retention of cardiovascular anatomy using transthoracic echocardiography.

With increasing medical knowledge, procedural, and diagnostic skills to learn, it is vital for educators to make the limited amount of teaching time available to students effective and efficient. Generative retrieval is an effective and efficient learning tool, improving long-term retention through the practice of retrieval from memory. Forty medical students were randomized to learn normal cardiovascular anatomy using transthoracic echocardiography video clips in a generative retrieval (GR) or standard practice (SP) group. GR participants were required to verbally identify each unlabeled cardiovascular structure after viewing the video. After answering, participants viewed the correctly labeled video. SP participants viewed the same video clips labeled with the correct cardiovascular structure for the same amount of total time without verbally generating an answer. All participants were tested for intermediate (1-wk), late (1-mo), and long-term (6- to 9-mo) retention of cardiovascular anatomy. Additionally, a three-question survey was incorporated to assess perceptions of the learning method. There was no difference in pretest scores. The GR group demonstrated a trend toward improvement in recall at 1 wk [GR = 74.3 (SD 12.3); SP = 65.4 (SD 16.7); P = 0.10] and 1 mo [GR = 69.9 (SD15.6); SP = 64.3 (SD 15.4); P = 0.33]. At the 6- to 9-mo time point, there was a statistically significant difference in scores [GR = 74.3 (SD 9.9); SP = 65.0 (SD 14.1); P = 0.042]. At nearly every time point, learners had a statistically significantly higher perception of effectiveness, enjoyment, and satisfaction with GR. In addition to improved recall, GR is associated with increased perceptions of effectiveness, enjoyment, and satisfaction, which may lead to increased engagement, time spent studying, and improved retention.

Depressive Symptoms Are Associated with Self-Reported Physical Limitations That Are Activity Dependent in a Cross-Sectional Analysis of Subjects with Chronic Obstructive Pulmonary Disease.

One in four patients with chronic obstructive pulmonary disease (COPD) has depression. However, the effect of depressive symptoms on self-reported physical function among patients with COPD is not fully defined. We tested the hypothesis that depressive symptoms among patients with COPD are associated with increased self-reporting of physical limitations in a nationally representative sample of adults living in the USA. We sampled 775 adults with obstructive lung disease and history of regular smoking from 2007 to 2012 National Health and Nutrition Examination Survey (NHANES). Multivariable logistic regression was used to estimate odds ratios for the association between depressive symptoms and self-reported difficulty performing three activities. We used a Patient Health Questionnaire (PHQ-9) score ≥ 10 to define depressive symptoms. Covariates in the multivariable analysis were age, gender, percent predicted forced expiratory volume in 1 second, current smoking, low-income status, and number of co-morbidities. In models predicting any difficulty walking a quarter mile, walking up 10 stairs, and walking between rooms on a level surface, adjusted odds ratio estimates (95% CI) for depressive symptoms were 2.03 (1.06, 3.88), 3.40 (1.77, 6.50), and 4.92 (2.29, 10.60), respectively. The presence of depressive symptoms was associated with increased self-reported difficulty with physical activities in our sample. Unexpectedly, the effect of depressive symptoms was greater with easier activities in our sample. These results suggest that depressive symptoms are associated with activity-dependent self-reporting of physical limitations among patients with COPD.

Clofarabine Plus Busulfan is an Effective Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Lymphoblastic Leukemia: Long-Term Study Results.

We investigated the long-term safety and disease control data obtained with i.v. busulfan (Bu) combined with clofarabine (Clo) in patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (HSCT). A total of 107 patients, median age 38 years (range, 19 to 64 years) received a matched sibling donor (n = 52) or matched unrelated donor (n = 55) transplant for ALL in first complete remission (n = 62), second complete remission (n = 28), or more advanced disease (n = 17). Nearly one-half of the patients had a high-risk cytogenetic profile as defined by the presence of t(9;22) (n = 34), t(4;11) (n = 4), or complex cytogenetics (n = 7). Clo 40 mg/m2 was given once daily, with each dose followed by pharmacokinetically dosed Bu infused over 3 hours daily for 4 days, followed by hematopoietic cell infusion after 2 days of rest. The Bu dose was based on the drug clearance as determined by a test Bu dose of 32 mg/m2. The target daily area under the curve was 5500 µmol/min for patients aged <60 years and 4000 µmol/min for patients aged >59 years. With a median follow-up of 3.3 years among surviving patients (range, 1 to 5.8 years), the 2-year progression-free survival (PFS) for patients undergoing HSCT in first complete remission (CR1), second complete remission (CR2), or more advanced disease was 62%, 34%, and 35%, respectively. The regimen was well tolerated, with nonrelapse mortality (NRM) of 10% at 100 days and 31% at 2 years post-HSCT. The incidence of grade II-IV and III-IV acute graft-versus-host disease (GVHD) was 35% and 10%, respectively; 18% patients developed extensive chronic GVHD. The 2-year overall survival (OS) for patients undergoing HSCT in CR1, CR2, or more advanced disease was 70%, 57%, and 35%, respectively. Among 11 patients aged >59 years treated with reduced-dose Bu in CR1 (n = 7) or CR2 (n = 4), 4 remain alive and disease-free, with a median follow-up of 2.6 years (range, 2 to 4.7 years). Only the presence of minimal residual disease at the time of transplantation was associated with significantly worse PFS and OS in multivariate analysis. Our data indicate that the Clo-Bu combination provides effective disease control while maintaining a favorable safety profile. OS and NRM rates compare favorably with those for traditional myeloablative total body irradiation-based conditioning regimens.

Pre-transplantation minimal residual disease with cytogenetic and molecular diagnostic features improves risk stratification in acute myeloid leukemia.

Our aim was to improve outcome prediction after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia by combining cytogenetic and molecular data at diagnosis with minimal residual disease assessment by multicolor flow-cytometry at transplantation. Patients with acute myeloid leukemia in first complete remission in whom minimal residual disease was assessed at transplantation were included and categorized according to the European LeukemiaNet classification. The primary outcome was 1-year relapse incidence after transplantation. Of 152 patients eligible, 48 had minimal residual disease at the time of their transplant. Minimal residual disease-positive patients were older, required more therapy to achieve first remission, were more likely to have incomplete recovery of blood counts and had more adverse risk features by cytogenetics. Relapse incidence at 1 year was higher in patients with minimal residual disease (32.6% versus 14.4%, P=0.002). Leukemia-free survival (43.6% versus 64%, P=0.007) and overall survival (48.8% versus 66.9%, P=0.008) rates were also inferior in patients with minimal residual disease. In multivariable analysis, minimal residual disease status at transplantation independently predicted 1-year relapse incidence, identifying a subgroup of intermediate-risk patients, according to the European LeukemiaNet classification, with a particularly poor outcome. Assessment of minimal residual disease at transplantation in combination with cytogenetic and molecular findings provides powerful independent prognostic information in acute myeloid leukemia, lending support to the incorporation of minimal residual disease detection to refine risk stratification and develop a more individualized approach during hematopoietic stem cell transplantation.

Impact of androgen receptor expression in fluoxymesterone-treated estrogen receptor-positive metastatic breast cancer refractory to contemporary hormonal therapy.

PURPOSE: The purpose of this study is to evaluate survival outcome in patients with hormone receptor (HR)-positive (+) metastatic breast cancer (MBC) who received fluoxymesterone after disease progression while receiving contemporary hormonal therapy, as well as the association between estrogen receptor (ER)/androgen receptor (AR) status and survival outcome in these patients. METHODS: We retrospectively identified 103 patients treated with fluoxymesterone for HR + MBC from 2000 to 2014 and with at least one previous hormonal therapy in a metastatic setting. RESULTS: A median of 3 (range 1-10) hormonal therapies (aromatase inhibitors, tamoxifen, and/or fulvestrant) were received before fluoxymesterone; 33 patients discontinued fluoxymesterone before progression because of physician decision or adverse events including toxicity in 14 patients. Of the remaining 70 patients, 2 (3 %) had complete response, 7 (10 %) partial response, and 21 (30 %) stable disease for at least 6 months, yielding a clinical benefit rate of 43 %. The median PFS was 3.9 months (95 % CI 3.2-5.3 months). Multivariate analysis revealed no significant association between PFS and the type or number of prior systemic treatments. All 39 patients who had archived tumor slides available for AR staining had ER + carcinoma; 10 had ≥1 % but <10 %, 18 had ≥10 %, and 11 had no AR nuclear expression. AR positivity with various cutoffs (i.e. any AR + cells, ≥1 % AR + cells, or ≥10 % AR + cells) was not significantly associated with survival outcome. CONCLUSIONS: Fluoxymesterone can be considered for patients whose ER + MBC progresses on contemporary hormonal therapy, regardless of the level of AR expression.

Operative and Oncologic Outcomes in 9861 Patients with Operable Breast Cancer: Single-Institution Analysis of Breast Conservation with Oncoplastic Reconstruction.

BACKGROUND: Oncoplastic reconstruction is an approach that enables patients with locally advanced or adversely located tumors to undergo breast conserving surgery (BCS). The objectives were to identify the use of BCS with oncoplastic reconstruction (BCS + R) and determine the operative and oncologic outcomes compared with other breast surgical procedures for breast cancer. METHODS: This retrospective cohort study interrogated a single institution's prospectively maintained databases to identify patients who underwent surgery for breast cancer between 2007 and 2014. Surgeries were categorized as BCS, BCS + R, total mastectomy (TM), or TM with immediate reconstruction (TM + R). Demographic and clinicopathologic characteristics and postoperative complications were analyzed. RESULTS: There were 10,607 operations performed for 9861 patients. Median follow-up was 3.4 years (range, 0-9.1 years). The use of BCS + R had a nearly fourfold increase in the percentage of all breast cancer surgeries during the study period; 75 % of patients who underwent BCS + R had a T1 or T2 tumor. There was no difference in the use of BCS + R compared with BCS for any quadrant of the breast except the lower outer quadrant (11.1 vs. 6.8 %; p < .0001). BCS + R had a lower rate of seroma formation (13.4 vs. 18 %; p = .002) and positive or close margins compared with BCS (5.8 vs. 8.3 %; p = .04). There was no difference in overall survival or recurrence-free survival when comparing BCS and BCS + R. CONCLUSIONS: Patients undergoing BCS + R are not disadvantaged in terms of complications and short-term (3-year) outcomes compared with BCS patients or patients who underwent TM.