An efficient penalized estimation approach for semiparametric linear transformation models with interval-censored data.

We consider efficient estimation of flexible transformation models with interval-censored data. To reduce the dimension of semiparametric models, the unknown monotone function is approximated via a monotone B-spline. A penalization technique is used to provide computationally efficient estimation of all parameters. To accomplish model fitting and inference, an easy to implement nested iterative expectation-maximization (EM) algorithm is developed for estimation, and a simple variance-covariance estimation approach is proposed which makes large-sample inference for the regression parameters possible. Theoretically, we show that the estimator of the unknown monotone increasing function achieves the optimal rate of convergence, and the estimators of the regression parameters are asymptotically normal and efficient under the appropriate selection of the order of the smoothing parameter and the knots of the spline space. The proposed penalized procedure is assessed through extensive numerical experiments and implemented in R package PenIC. The proposed methodology is further illustrated via a signal tandmobiel study.

Instruments to measure e-cigarette related constructs: a systematic review.

BACKGROUND: Electronic cigarettes (e-cigarettes) are relatively new tobacco products that are attracting public attention due to their unique features, especially their many flavor options and their potential as an alternative to cigarettes. However, uncertainties remain regarding the determinants and consequences of e-cigarette use because current research on e-cigarettes is made more difficult due to the lack of psychometrically sound instruments that measure e-cigarette related constructs. This systematic review therefore seeks to identify the instruments in the field that are designed to assess various aspects of e-cigarette use or its related constructs and analyze the evidence presented regarding the psychometric properties of the identified instruments. METHODS: This systematic review utilized six search engines: PubMed, Medline, CINAHL, PsycINFO, Web of Science, and EMBASE, to identify articles published in the peer-reviewed journals from inception to February 2022 that contained development or validation processes for these instruments. RESULTS: Eighteen articles describing the development or validation of 22 unique instruments were identified. Beliefs, perceptions, motives, e-cigarette use, and dependence, were the most commonly assessed e-cigarette related constructs. The included studies reported either construct or criterion validity, with 14 studies reporting both. Most studies did not report the content validity; for reliability, most reported internal consistencies using Cronbach's alpha, with 15 instruments reporting Cronbach's alpha > 0.70 for the scale or its subscales. CONCLUSIONS: Twenty-two instruments with a reported development or validation process to measure e-cigarette related constructs are currently available for practitioners and researchers. This review provides a guide for practitioners and researchers seeking to identify the most appropriate existing instruments on e-cigarette use based on the constructs examined, target population, psychometric properties, and instrument length. The gaps identified in the existing e-cigarette related instruments indicate that future studies should seek to extend the validity of the instruments for diverse populations, including adolescents. Instruments that explore additional aspects of e-cigarette use and e-cigarette related constructs to help build a strong theoretical background and expand our current understanding of e-cigarette use and its related constructs, should also be developed.

COMFORT communication in the ICU: Pilot test of a nurse-led communication intervention for surrogates.

AIM: This study was designed to investigate the feasibility, acceptability, and preliminary efficacy of a nurse-led communication intervention among surrogates in the intensive care unit (ICU) guided by the COMFORT (Connect; Options; Making meaning; Family caregivers; Openings; Relating; Team) communication model. BACKGROUND: As frontline communicators, nurses experience communication difficulties with surrogates who face complex informational and emotional barriers when making decisions for critically ill patients in the ICU. However, research on effective nurse communication focusing on both curative and end-of-life (EOL) care is lacking in the literature. DESIGN: A single-centre two-group pretest-posttest quasi-experiment. METHOD: The total sample included 41 surrogates of adult ventilated patients. Twenty participants were allocated to the intervention group who received a daily 20-min telephone call with content based on the COMFORT communication model. Twenty-one participants comprised the control group who received usual care. Participants completed a questionnaire before and after the study measuring satisfaction, anxiety and depression, decisional conflict, and quality of communication. The Transparent Reporting of Evaluations with Nonrandomized Designs (TREND) checklist was followed for nonrandomised controlled trials. RESULT: The intervention was feasible, with 19 of 20 surrogates completing the follow-up surveys, and 48 telephone conversations completed (48% of the planned phone calls). Surrogates' satisfaction was higher in the intervention group than in the control group after adjusting for the selected covariates (25.43 and 24.15, respectively; p = .512). Preliminary efficacy outcomes favouring the intervention included quality of communication with healthcare providers, but not surrogates' perceived depression/anxiety and decisional conflicts. CONCLUSION: Implementation of the intervention is feasible, acceptable, and favourable among surrogates to improve quality of communication with healthcare providers in the ICU. Further research is needed to determine whether the intervention could be implemented by nurses to improve surrogates' outcomes in other ICUs.

Dementia caregiver burdens predict overnight hospitalization and hospice utilization.

OBJECTIVES: To determine sociodemographics and caregiver burdens associated with overnight hospitalization, hospice utilization, and hospitalization frequency among persons with dementia (PWD). METHODS: Cross-sectional analysis of PWD (n = 899) of the National Health and Aging Trends Study linked to the National Study of Caregiving. Logistic and proportional odds regression determined the effects of caregiver burdens on overnight hospitalization, hospice use, and hospitalization frequency. Differences between PWD alive not-alive groups were compared on overnight hospitalization and frequency. RESULTS: Alive PWD (n = 804) were 2.36 times more likely to have an overnight hospital stay (p = 0.004) and 1.96 times more likely to have multiple hospitalizations when caregivers found it physically difficult to provide care (p = 0.011). Decedents aged 65-74 (n = 95) were 4.55 times more likely to experience overnight hospitalizations than 85+, hospitalizations were more frequent (odds ratio [OR] = 4.84), and there was a significant difference between PWD alive/not alive groups (p = 0.035). Decedents were 5.60 times more likely to experience an overnight hospitalization when their caregivers had financial difficulty, hospitalizations were more frequent when caregivers had too much to handle (OR = 8.44) and/or no time for themselves (OR = 10.67). When caregivers had no time for themselves, a significant difference between alive/not alive groups (p = 0.018) was detected in hospitalization frequency. PWD whose caregivers had emotional difficulty helping were 5.89 times more likely to utilize hospice than caregivers who did not report emotional difficulty. SIGNIFICANCE OF RESULTS: Care transitions among PWD at the end of life are impacted by the circumstances and experiences of their caregivers. Subjective caregiver burdens represent potentially modifiable risks for undesired care transitions and opportunities for promoting hospice use. Future work is warranted to identify and address these issues as they occur.

Radiotherapy is Associated With Improved Survival in Patients With Synovial Sarcoma Undergoing Surgery: A National Cancer Database Analysis.

BACKGROUND: Previous studies have demonstrated an association of perioperative radiotherapy (RT) with improved survival in patients with synovial sarcoma (SS) undergoing surgery, but the mechanism for this is unknown. In this study, we sought to further analyze this association using a hospital-based data set where data on chemotherapy administration and surgical margin status are available. METHODS: Using the National Cancer Database, we identified 1216 patients with SS (aged ≥18 y) from 2004-2012 undergoing surgery. Cox proportional hazards analysis was used to study the effect of clinicopathologic variables on overall survival (OS). RESULTS: Mean age at diagnosis was 41.5 y (range 18-90), and 71.3% of tumors were high grade; 22.9% underwent surgery alone, 59.6% received RT with surgery, 44.2% received chemotherapy with surgery, and 26.3% received trimodality therapy. Age, sex, grade, Charlson-Deyo score, and RT (hazard ratio, 0.676; 95% confidence interval, 0.519-0.880; P = 0.004) were associated with improved OS, whereas chemotherapy (hazard ratio, 1.20; 95% confidence interval, 0.899-1.60; P = 0.217) and surgical margin status were not. Trimodality therapy with surgery, RT, and chemotherapy was associated with improved OS when compared with therapy with surgery and chemotherapy alone. CONCLUSIONS: In patients with SS undergoing surgery, we observed a significant improved association of OS with the addition of RT when adjusting for comorbidity score, margin status, and receipt of chemotherapy. These data further support routine implementation of RT in the treatment of patients with SS, including those receiving aggressive multimodality and trimodality care.

Racial disparities of Black Americans hospitalized for decompensated liver cirrhosis.

BACKGROUND: Racial disparities have been reported in liver transplantation and chronic hepatitis C treatment outcomes. Determining causes of these disparities is important given the racially diverse American population and the economic burden associated with chronic liver disease. METHODS: A retrospective study was performed among 463 patients diagnosed with cirrhosis admitted from (January 1, 2013 to January 1, 2018) to a tertiary care academic medical center. Patients were identified based on the International Classification of Diseases (ICD-10) for cirrhosis or its complications. Demographic information, laboratory data, medical comorbidities, insurance and adherence to cirrhosis quality care indicators were recorded to determine their relationship to readmission rates and other healthcare outcomes. RESULTS: A total of 463 individual patients with cirrhosis were identified including Whites (n = 241), Hispanics (n = 106), Blacks (n = 50), Asian and Pacific Islander Americans (API, n = 27) and Other (n = 39). A significantly higher proportion of Blacks had Medicaid insurance compared to Whites (40% versus 20%, p = 0.0002) and Blacks had lower median income than Whites ($45,710 versus $54,844, p = 0.01). All groups received high quality cirrhosis care. Regarding healthcare outcomes, Black patients had the highest mean total hospital admissions (6.1 ± 6.3, p = 0.01) and the highest mean number of 30-day re-admissions (2.1 ± 3.7, p = 0.05) compared to all other racial groups. Multivariable proportional odds regression analysis showed that race was a statistically significant predictor of 90-day readmission (p = 0.03). CONCLUSIONS: Black Americans hospitalized for complications of cirrhosis may experience significant disparities in healthcare outcomes compared to Whites despite high quality cirrhosis care. Socioeconomic factors may contribute to these disparities.

Healthcare Disparities Identified Between Hmong and Other Asian Origin Groups Living with Chronic Hepatitis B Infection in Sacramento County 2014-2017.

Chronic hepatitis B (CHB) disproportionately affects non-US born Asians. The Hmong have been shown to have the highest rates of CHB and mortality from liver cancer compared to other Asian groups. From September 2014 to September 2017, testing for CHB within Sacramento County was conducted through community-based testing events and an electronic health record alert that identified Asian patients by surname. Demographic and laboratory data were collected for analysis and patients were followed through the study period to assess linkage to care and treatment to compare differences between Asian origin groups. Of 4350 patients tested for CHB, 318 (7.3%) were HBsAg positive, including 90 Chinese, 47 Hmong, and 101 Vietnamese. Hmong were more likely to have Medicaid insurance compared to other Asian origin groups (15%, p < 0.001). Hmong had significantly lower rates of hepatitis B DNA testing (p < 0.001), referral to hepatology (p < 0.001), attendance of first (p < 0.001) and second medical visit (p = 0.0003), and lower rates of antiviral treatment compared to other Asian origin groups. Hmong also had the highest proportion of non-English speakers (p < 0.001). Hmong patients in the Sacramento CHB testing and linkage to care program experience socioeconomic disadvantages compared to Vietnamese and Chinese patients. These factors may contribute to decreased linkage of care and decreased anti-viral treatment rates for CHB.

Assessing the Similarity between Random Copolymer Drug Glatiramer Acetate by Using LC-MS Data Coupling with Hypothesis Testing.

The full characterization of nonbiological complex drugs (NBCDs) is not possible, but analytical approaches are of urgent need to evaluate the similarity between different lots and compare with their follow-up versions. Here, we propose a hypothesis testing-based approach to assess the similarity/difference between random amino acid copolymer drugs using liquid chromatography mass spectrometry (LC-MS) analysis. Two glatiramer acetate (GA) drugs, commercially available Copaxone and in-house synthesized SPT, and a negative control were digested by Lys-C and followed by HILIC-MS analysis. After retention time alignment and feature identification, 1627 features matched to m/z values in an elemental composition database were considered as derived from active drug ingredients. A hypothesis testing approach, the sum of squared deviations test, was developed to process high-dimensional data derived from LC-MS spectra. The feasibility of this approach was first demonstrated by testing 5 versus 5 lots of Copaxone and Copaxone versus SPT, which suggested a significant similarity by obtaining the estimated 95th percentile of the distribution of the estimator (ρ̂(95%)) at 0.0056 (p-value = 0.0026) and 0.0026 (p-value < 0.0001), respectively. In contrast, the ρ̂ was 0.036 (p-value = 1.00), while comparing Copaxone and the negative control, implying a lack of similarity. We further synthesized nine stable isotope-labeled peptides to validate the proposed amino acid sequences in the database, demonstrating the correctness in sequence identification. The quantitation variations in our analytical procedures were determined to be 6.8-7.7%. This approach was found to have a great potential for evaluating the similarity between generic NBCDs and listed reference drugs, as well as to monitor the lot-to-lot variation.

Impaired proteostasis in senescent vascular endothelial cells: a perspective on estrogen and oxidative stress in the aging vasculature.

The heat shock response is an important cytoprotective mechanism for protein homeostasis and is an essential protective response to cellular stress and injury. Studies on changes in the heat shock response with aging have been mixed with regard to whether it is inhibited, and this, at least in part, reflects different tissues and different models. Cellular senescence is a key feature in aging, but work on the heat shock response in cultured senescent (SEN) cells has largely been limited to fibroblasts. Given the prevalence of oxidative injury in the aging cardiovascular system, we investigated whether SEN primary human coronary artery endothelial cells have a diminished heat shock response and impaired proteostasis. In addition, we tested whether this downregulation of heat shock response can be mitigated by 17ß-estradiol (E2), which has a critical cardioprotective role in women, as we have previously reported that E2 improves the heat shock response in endothelial cells (Hamilton KL, Mbai FN, Gupta S, Knowlton AA. Arterioscler Thromb Vasc Biol 24: 1628-1633, 2004). We found that SEN endothelial cells, despite their unexpectedly increased proteasome activity, had a diminished heat shock response and had more protein aggregation than early passage cells. SEN cells had increased oxidative stress, which promoted protein aggregation. E2 treatment did not decrease protein aggregation or improve the heat shock response in either early passage or SEN cells. In summary, cellular senescence in adult human endothelial cells is accompanied by increased oxidative stress and a blunting of proteostasis, and E2 did not mitigate these changes. NEW & NOTEWORTHY Senescent human endothelial cells have a diminished heat shock response and increased protein aggregates. Senescent human endothelial cells have increased basal oxidative stress, which increases protein aggregates. Physiological level of 17ß-estradiol did not improve proteostasis in endothelial cells.

Interhospital Variability in Quality Outcomes of Pancreatic Surgery.

BACKGROUND: Assessment of optimal patient outcomes from health care delivery is critical for success amidst current reform. We developed a composite index of quality for pancreaticoduodenectomy (PD) and compared high and low performers nationwide. METHODS: We performed a retrospective analysis of 17,220 patients undergoing elective PD between October 2010 and June 2014 using the Vizient database. A quality index score (QIS) was developed from five variables associated with optimal outcomes: postoperative complication rate, length of stay, 30-d readmission rate, mortality rate, and hospital volume. Value was defined as hospital-based QIS divided by mean hospital charges. High-value centers (top quintile) were compared to low-value centers (bottom quintile). RESULTS: The majority of high-value centers (79%) achieved top performer status in 1-2 of five quality categories though only 11% were low performer in at least one category. Conversely, 41% of low-value centers were top performers in at least one category, although rarely more than one (8%); 63% of low-value centers were low performers in two or more categories. There was no significant association between QIS and hospital charges (-570, 95% CI -1308 to 168, P = 0.13). CONCLUSIONS: High-value centers infrequently provided high quality surgical care across all five metrics but instead excelled in a few quality metrics while avoiding low performance in any quality metric. Although low-value centers could achieve excellence in one quality metric, they were frequently low performers in two or more outcomes. Improvements in value of PD can be achieved by a consistent effort across all quality metrics rather than efforts at constraining financial expenditures of health care delivery.

Quantification of ultraviolet (UV) radiation in the shade and in direct sunlight.

Ultraviolet (UV) radiation is associated with negative health effects, including sun damage and skin cancer. The purpose of this study is to compare the protective effects of the shade provided by a sun umbrella versus that provided by a tree. Sun sensors that register the level and dose of UV radiation were placed in the shade and in direct sunlight. Measurements were recorded every half hour between the hours of 12:30 p.m. and 3:00 p.m. in Sacramento, California. The results suggest that the level of UV radiation in the shade is not zero. The sensors located in tree shade indicated that over 5% of UV radiation was detected in the shade. The sensors located in sun-umbrella shade showed that greater than 17% of UV radiation reached the shade. The sun sensors used in our study collected UV radiation data relevant to UV index; however, they did not differentiate between UVA, UVB, visible, and infrared light. The amount of UV radiation detected in the shade is not zero, thus regular sunscreen use and other sun protective practices should be followed to reduce the risk of sun damage and skin cancer.

Effect of antiretroviral therapy on allele-associated Lp(a) level in women with HIV in the Women's Interagency HIV Study.

We previously demonstrated an association between lipoprotein (a) [Lp(a)] levels and atherosclerosis in human immunodeficiency virus (HIV)-seropositive women. The effects of antiretroviral therapy (ART) on Lp(a) levels in relation to apo(a) size polymorphism remain unclear. ART effects on allele-specific apo(a) level (ASL), an Lp(a) level associated with individual apo(a) alleles within each allele-pair, were determined in 126 HIV-seropositive women. ART effects were tested by a mixed-effects model across pre-ART and post-ART first and third visits. Data from 120 HIV-seronegative women were used. The mean age was 38 years; most were African-American (∼70%). Pre-ART ASLs associated with the larger (4.6 mg/dl vs. 8.0 mg/dl, P = 0.024) or smaller (13 mg/dl vs. 19 mg/dl, P = 0.041) apo(a) sizes were lower in the HIV-seropositive versus HIV-seronegative group, as was the prevalence of a high Lp(a) level (P = 0.013). Post-ART ASL and prevalence of high Lp(a) or apo(a) sizes and frequency of small size apo(a) (22 kringles) did not differ between the two groups. ART increased Lp(a) level (from 18 to 24 mg/dl, P < 0.0001) and both ASLs (P < 0.001). In conclusion, regardless of genetic control, Lp(a) can be modulated by HIV and its treatment. ART initiation abrogates HIV-induced suppression of Lp(a) levels and ASLs, contributing to promote CVD risk in HIV-seropositive individuals.

Impact of a smoke-free-living educational intervention for smokers and household nonsmokers: A randomized trial of Chinese American pairs.

BACKGROUND: Chinese American men smoke at a high rate, which puts household nonsmokers at risk. The objective of this study was to evaluate the effectiveness of a brief-intensity versus moderate-intensity smoke-free-living educational intervention for household pairs. METHODS: The authors conducted a randomized controlled trial of Cantonese-speaking Chinese American smoker and household nonsmoker pairs in San Francisco, California. Pairs were randomized to moderate-intensity or brief-intensity group sessions with their household partner. The moderate-intensity group received 2 group sessions, a laboratory report of their baseline smoke exposure, as measured by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and 3 follow-up calls over 6 months. The brief-intensity group received 1 group session on tobacco-cessation resources. Primary outcomes were biochemically validated, past-month smoking abstinence and elimination of nonsmoker household exposure at 12 months. RESULTS: Participant pairs (n = 203) were male smokers, one-half of whom did not intend to quit within 6 months, with mostly female spouses as household nonsmokers. Approximately three-quarters of nonsmokers in both groups already had smoke-free home rules. At 12 months, smokers in both groups had similar biochemically validated 30-day abstinence rates (moderate-intensity group, 0%-20.7%; brief-intensity group, 0%-20.0%; P = .002 over time). More smokers in the moderate-intensity group used subsequent cessation group classes (moderate-intensity group, 50%; brief-intensity group, 24%; P = .004). Household nonsmokers in both groups had similar biochemically validated rates of no home exposure (moderate-intensity group, 24.5%-42.2%; brief-intensity group, 24.8%-33.3%; P = .0001 over time). CONCLUSIONS: A moderate-intensity smoke-free-living educational intervention for Chinese-speaking household pairs was not more effective than a brief-intensity intervention for smoking abstinence and elimination of household nonsmoker exposure. Abstinence rates were similar to those achieved with standard group counseling. Cancer 2018;124:1590-8. © 2018 American Cancer Society.

Aspirin and clopidogrel high on-treatment platelet reactivity and genetic predictors in peripheral arterial disease.

OBJECTIVES: Our aims were to examine the prevalence and genetic predictors of aspirin and clopidogrel high on-treatment platelet reactivity (HoTPR), and associated adverse cardiovascular outcomes in patients with peripheral arterial disease (PAD). BACKGROUND: The association of aspirin and clopidogrel HoTPR with outcomes in PAD remains unclear. METHODS: This is a prospective cohort study of patients with angiographically documented PAD involving carotid and lower extremity arteries. Aspirin and clopidogrel HoTPR (using the VerifyNow Assay) and associated genetic predictors were compared to clinical outcomes. The primary end-point was a composite of major adverse cardiovascular events: all-cause mortality, myocardial infarction, stroke, target vessel revascularization (TVR) and limb-loss in patients who underwent extremity intervention. RESULTS: The study was stopped prematurely due to slow patient enrolment. Of 195 patients enrolled, the primary analysis was performed in 154 patients taking both drugs. Aspirin HoTPR was present in 31 (20%) and clopidogrel HoTPR in 76 (49%) patients. There was a trend toward more primary composite outcome events with PRU ≥ 235 (52% freedom-from-event rate vs. 70% for PRU < 235; P = 0.09). TVR was higher in those with PRU ≥ 235 (20 vs. 6%, unadjusted P = 0.02). There was no association between aspirin HoTPR and combined outcomes. Single nucleotide polymorphisms in serum paraoxonase/arylesterase 1 (PON1) gene was associated with aspirin HoTPR (P = 0.005) while SNP in phospholipase A2, group III (PLA2G3) gene was associated with clopidogrel HoTPR (P = 0.002). CONCLUSION: Clopidogrel HoTPR was significantly associated with TVR, while aspirin HoTPR was not associated with adverse clinical outcomes in patients with PAD.

Alterations in cancer stem-cell marker CD44 expression predict oncologic outcome in soft-tissue sarcomas.

BACKGROUND: Cancer stem cells (CSCs) have been shown to resist chemotherapy and promote metastasis after cytotoxic therapies. We sought to determine if the expression of CSC markers (aldehyde dehydrogenase [ALDH], CD44, and epidermal growth factor receptor [EGFR]) predicted outcomes in soft-tissue sarcoma (STS) patients. METHODS: We queried an institutional database of 23 STS patients and evaluated immunohistochemical expression of CSC markers ALDH, CD44, and EGFR. The Cancer Genome Atlas (TCGA) was also queried for STS clinical and genomic data. Disease-specific (DSS) and overall survival (OS) were assessed by univariate and Kaplan-Meier analysis. RESULTS: Of the 23 institutional patients, the majority was female, had high-grade tumors and had extremity tumors. With a median follow-up of 27 months, nine patients (39%) experienced distant recurrence, and four (17%) died of disease. Mean H-scores at diagnosis (±standard error of the mean) for CD44, ALDH1, and EGFR were 169 ± 27, 77 ± 15, and 144 ± 23, respectively. On univariate analysis, there was a trend for increased CD44 score to predict both worse DSS and OS (hazard ratio = 1.01, 95% confidence interval 1-1.02, P = 0.056), whereas ALDH and EGFR scores did not. Analysis of 74 TCGA STS cases with complete clinical and genomic data revealed that CD44 copy number alterations predicted worse DSS (9.89 months versus 72.5 months, P = 0.007) and a trend for worse OS (14.03 months versus 38.6 months, P = 0.12), whereas ALDH1 and EGFR copy number alteration did not. Multivariate analysis of the combined data sets was consistent with worse DSS among patients with higher CD44 expression. CONCLUSIONS: Institutional and national TCGA data show the association of elevated baseline CD44 expression with worse STS outcomes. Further study of CD44 as a possible novel STS biomarker appears indicated.

Lipoprotein(a) and HIV: Allele-Specific Apolipoprotein(a) Levels Predict Carotid Intima-Media Thickness in HIV-Infected Young Women in the Women's Interagency HIV Study.

OBJECTIVE: In the general population, lipoprotein(a) [Lp(a)] has been established as an independent causal risk factor for cardiovascular disease. Lp(a) levels are to a major extent regulated by a size polymorphism in the apolipoprotein(a) [apo(a)] gene. The roles of Lp(a)/apo(a) in human immunodeficiency virus (HIV)-related elevated cardiovascular disease risk remain unclear. APPROACH AND RESULTS: The associations between total plasma Lp(a) level, allele-specific apo(a) level, an Lp(a) level carried by individual apo(a) alleles, and common carotid artery intima-media thickness were assessed in 150 HIV-infected and 100 HIV-uninfected women in the WIHS (Women's Interagency HIV Study). Linear regression analyses with and without adjustments were used. The cohort was young (mean age, ≈31 years), with the majority being Blacks (≈70%). The prevalence of a small size apo(a) (≤22 Kringle repeats) or a high Lp(a) level (≥30 mg/dL) was similar by HIV status. Total plasma Lp(a) level (P=0.029) and allele-specific apo(a) level carried by the smaller apo(a) sizes (P=0.022) were significantly associated with carotid artery intima-media thickness in the HIV-infected women only. After accounting for confounders (age, race, smoking, body mass index, blood pressure, hepatitis C virus coinfection, menopause, plasma lipids, treatment status, CD4+ T cell count, and HIV/RNA viral load), the association remained significant for both Lp(a) (P=0.035) and allele-specific apo(a) level carried by the smaller apo(a) sizes (P=0.010) in the HIV-infected women. Notably, none of the other lipids/lipoproteins was associated with carotid artery intima-media thickness. CONCLUSIONS: Lp(a) and allele-specific apo(a) levels predict carotid artery intima-media thickness in HIV-infected young women. Further research is needed to identify underlying mechanisms of an increased Lp(a) atherogenicity in HIV infection.

Advancing Simulation-Based Education in Pain Medicine.

Background: The Accreditation Council for Graduate Medical Education (ACGME) has recently implemented milestones and competencies as a framework for training fellows in Pain Medicine, but individual programs are left to create educational platforms and assessment tools that meet ACGME standards. Objectives: In this article, we discuss the concept of milestone-based competencies and the inherent challenges for implementation in pain medicine. We consider simulation-based education (SBE) as a potential tool for the field to meet ACGME goals through advancing novel learning opportunities, engaging in clinically relevant scenarios, and mastering technical and nontechnical skills. Results: The sparse literature on SBE in pain medicine is highlighted, and we describe our pilot experience, which exemplifies a nascent effort that encountered early difficulties in implementing and refining an SBE program. Conclusions: The many complexities in offering a sophisticated simulated pain curriculum that is valid, reliable, feasible, and acceptable to learners and teachers may only be overcome with coordinated and collaborative efforts among pain medicine training programs and governing institutions.

Adiposity and weight gain during pregnancy associate independently with behavior of infant rhesus monkeys (Macaca mulatta).

Growing evidence identifies maternal adiposity as a potentially modifiable risk factor for adverse neurodevelopment. This retrospective cohort analysis examined whether maternal prepregnancy adiposity and gestational weight gain were associated with behavioral outcomes in 173 rhesus macaque infants at the California National Primate Research Center. Dams conceived indoors, had uncomplicated pregnancies, delivered vaginally, and reared infants indoors. Infants underwent standardized biobehavioral analysis at 90-120 days of age from 3/2001-5/2015. Offspring of mothers with greater baseline adiposity or gestational weight gain exhibited a pattern of poor adaptability characterized by greater emotionality as the assessments proceeded, blunted affective response to a human intruder challenge, and reduced interest in novel stimuli which is associated with poorer social functioning later in life. They also had lower cortisol levels following dexamethasone suppression, perhaps a response to cortisol excess during gestation. These results amplify growing public health concerns implicating maternal adiposity in impaired fetal neurobehavioral programming.

Penalized estimation for proportional hazards models with current status data.

We provide a simple and practical, yet flexible, penalized estimation method for a Cox proportional hazards model with current status data. We approximate the baseline cumulative hazard function by monotone B-splines and use a hybrid approach based on the Fisher-scoring algorithm and the isotonic regression to compute the penalized estimates. We show that the penalized estimator of the nonparametric component achieves the optimal rate of convergence under some smooth conditions and that the estimators of the regression parameters are asymptotically normal and efficient. Moreover, a simple variance estimation method is considered for inference on the regression parameters. We perform 2 extensive Monte Carlo studies to evaluate the finite-sample performance of the penalized approach and compare it with the 3 competing R packages: C1.coxph, intcox, and ICsurv. A goodness-of-fit test and model diagnostics are also discussed. The methodology is illustrated with 2 real applications.

Predictors of residual disease after unplanned excision of soft tissue sarcomas.

BACKGROUND: Unplanned excision of soft tissue sarcomas (STS) is an important quality of care issue given the morbidity related to tumor bed excision. Since not all patients harbor residual disease at the time of reexcision, we sought to determine predictors of residual STS following unplanned excision. METHODS: We identified 76 patients from a prospective database (January 1, 2008-September 30, 2014) who received a diagnosis of primary STS following unplanned excision on the trunk or extremities. We used univariable and multivariable analyses to evaluate predictors of residual STS as the primary endpoint. We calculated the sensitivity, specificity, and accuracy of interval magnetic resonance imaging (MRI) to predict residual sarcoma at reexcision. RESULTS: Mean age was 52 y, and 63.2% were male. 50% had fragmented unplanned excision. Among patients undergoing reexcision, residual STS was identified in 70%. On univariable analysis, MRI showing gross disease and fragmented excision were significant predictors of residual STS (odds ratio, 10.59; 95% CI, 2.14-52.49; P = 0.004 and odds ratio, 3.61; 95% CI, 1.09-11.94; P = 0.035, respectively). On multivariable analysis, tumor size predicted distant recurrence and overall survival. When we combined equivocal and positive MRI, the sensitivity and specificity of MRI for predicting residual STS were 86.7% (95% CI, 73.2%-95.0%) and 57.9% (95% CI, 33.5%-79.8%), with an overall accuracy of 78.1% (95% CI, 66.0%-87.5%). CONCLUSIONS: About 70% of patients undergoing repeat excision after unplanned excision of STS harbor residual sarcoma. Although interval MRI and fragmented excision appear to be the most significant predictors of residual STS, the accuracy of MRI remains modest, especially given the incidence of equivocal MRI.