Surgeon views on firearm safety counseling in clinical practice: A cross-sectional survey.

BACKGROUND: Firearms are commonplace in the United States, and one proposed strategy to decrease risk of firearm injury is to have physicians counsel their patients about safe firearm ownership. Current rates of firearm safety counseling by surgeons who care for injured people are unknown. METHODS: This study used an anonymous cross-sectional survey derived from previously published survey instruments and was piloted (n = 13) at the annual meeting of the American Association for the Surgery of Trauma (2022). The finalized survey was distributed using a quick response code during two sessions at the 2022 American College of Surgeons Clinical Congress. Eligible participants included the surgeons and surgical trainees who attended these sessions. RESULTS: One hundred fourteen individuals completed the survey (20% response rate), and a majority were male (n = 71 [62.3%]), attending surgeons (n = 108 [94.7%]), and specialized in acute care surgery (n = 72 [63.2%]). Few participants (n = 43 [37.7%]) reported counseling patients on firearm safety as part of their routine clinical practice; however, the majority (n = 102 [89.5%]) believed that surgeons should provide firearm safety counseling. Counseling rates did not vary significantly by age, sex, surgical specialty, or region of practice, but attitudes toward counseling did differ by firearm safety counseling practices ( p = 0.03) and region of practice (0.04). Noted barriers to counseling included lack of time (n = 47 [41.2%]), perceived lack of training (n = 43 [37.7%]), and lack of firearm knowledge/experience (n = 36 [31.6%]). CONCLUSION: Most surgeon respondents did not provide firearm safety counseling to their patients despite the fact the majority believed they should. This suggests that counseling interventions that do not solely rely on surgeons for implementation could increase the number of patients who receive firearm safety guidance during clinical encounters. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Coinhibition of topoisomerase 1 and BRD4-mediated pause release selectively kills pancreatic cancer via readthrough transcription.

Pancreatic carcinoma lacks effective therapeutic strategies resulting in poor prognosis. Transcriptional dysregulation due to alterations in KRAS and MYC affects initiation, development, and survival of this tumor type. Using patient-derived xenografts of KRAS- and MYC-driven pancreatic carcinoma, we show that coinhibition of topoisomerase 1 (TOP1) and bromodomain-containing protein 4 (BRD4) synergistically induces tumor regression by targeting promoter pause release. Comparing the nascent transcriptome with the recruitment of elongation and termination factors, we found that coinhibition of TOP1 and BRD4 disrupts recruitment of transcription termination factors. Thus, RNA polymerases transcribe downstream of genes for hundreds of kilobases leading to readthrough transcription. This occurs during replication, perturbing replisome progression and inducing DNA damage. The synergistic effect of TOP1 + BRD4 inhibition is specific to cancer cells leaving normal cells unaffected, highlighting the tumor's vulnerability to transcriptional defects. This preclinical study provides a mechanistic understanding of the benefit of combining TOP1 and BRD4 inhibitors to treat pancreatic carcinomas addicted to oncogenic drivers of transcription and replication.

Mindfulness-based stress reduction for men on active surveillance for prostate cancer and their spouses: Design and methodology of a randomized controlled trial.

BACKGROUND: Although active surveillance (AS) is an increasingly adopted treatment paradigm for management of very low risk prostate cancer, many men and their partners face a variety of AS-related psychosocial stressors. Stressors may include anxiety and fear of progression, which may negatively affect short- and long-term psychosocial adjustment and influence early withdrawal from AS in order to seek definitive therapies such as surgery or radiation. Here we describe the protocol for an NCI-funded trial, which seeks to examine the efficacy of mindfulness training compared with a time/attention-matched health promotion control condition in a geographically generalizable sample of men on AS and their spouses. METHODS: Using a randomized, controlled, partially double-blinded study design, this study involves the delivery of 8 weeks of standardized mindfulness training (MBSR; mindfulness-based stress reduction) and patient reported outcomes over a 12-month period (proposed enrollment of 80 men on AS and spouses), compared with a health promotion control (proposed enrollment of 80 men on AS and spouses) that has been matched for time and attention. Baseline (T1) measures (e.g., anxiety, fear of progression, quality of life) are administered just prior to randomization to the two study arms, followed by repeated assessments at 2 months (T2), 6 months (T3) and 12 months (T4). CONCLUSION: This study has the potential to offer men and their partners on AS with important educational and self-regulatory skills to better cope and adjust with known stressors related to being placed on this protocol.

DNA damage, DNA repair and carcinogenicity: Tobacco smoke versus electronic cigarette aerosol.

The allure of tobacco smoking is linked to the instant gratification provided by inhaled nicotine. Unfortunately, tobacco curing and burning generates many mutagens including more than 70 carcinogens. There are two types of mutagens and carcinogens in tobacco smoke (TS): direct DNA damaging carcinogens and procarcinogens, which require metabolic activation to become DNA damaging. Recent studies provide three new insights on TS-induced DNA damage. First, two major types of TS DNA damage are induced by direct carcinogen aldehydes, cyclic-1,N2-hydroxy-deoxyguanosine (γ-OH-PdG) and α-methyl-1, N2-γ-OH-PdG, rather than by the procarcinogens, polycyclic aromatic hydrocarbons and aromatic amines. Second, TS reduces DNA repair proteins and activity levels. TS aldehydes also prevent procarcinogen activation. Based on these findings, we propose that aldehydes are major sources of TS induce DNA damage and a driving force for carcinogenesis. E-cigarettes (E-cigs) are designed to deliver nicotine in an aerosol state, without burning tobacco. E-cigarette aerosols (ECAs) contain nicotine, propylene glycol and vegetable glycerin. ECAs induce O6-methyl-deoxyguanosines (O6-medG) and cyclic γ-hydroxy-1,N2--propano-dG (γ-OH-PdG) in mouse lung, heart and bladder tissues and causes a reduction of DNA repair proteins and activity in lungs. Nicotine and nicotine-derived nitrosamine ketone (NNK) induce the same types of DNA adducts and cause DNA repair inhibition in human cells. After long-term exposure, ECAs induce lung adenocarcinoma and bladder urothelial hyperplasia in mice. We propose that E-cig nicotine can be nitrosated in mouse and human cells becoming nitrosamines, thereby causing two carcinogenic effects, induction of DNA damage and inhibition of DNA repair, and that ECA is carcinogenic in mice. Thus, this article reviews the newest literature on DNA adducts and DNA repair inhibition induced by nicotine and ECAs in mice and cultured human cells, and provides insights into ECA carcinogenicity in mice.

Early Physiological and Adrenal Effects of Budesonide Mixed with Surfactant in Large Observational Preterm Cohort Study.

BACKGROUND: The combination of surfactant and budesonide has been shown to decrease BPD rates and severity. Budesonide may be released systemically from lungs, and the effects on the immature adrenal glands are not known. OBJECTIVE: The aim of this study was to determine if adrenal suppression rates are higher in preterm infants receiving budesonide with surfactant compared to surfactant alone. METHODS: A retrospective chart review of 608 infants ≤1,250 g received intubation for surfactant therapy from 2013 through 2020. In August 2016, budesonide was added to surfactant for these infants. Indicators of adrenal suppression, including mean blood pressures, plasma electrolyte levels, hydrocortisone use, and the use of vasoactive medications, were analyzed for the first 14 days after birth. Respiratory variables, biochemical signs of adrenal insufficiency, and neonatal morbidities were analyzed. RESULTS: There was no difference in hydrocortisone administration in the first 14 days between infants receiving budesonide with surfactant (n = 314) or surfactant alone (n = 294) (23% vs. 19%, p = 0.38). Budesonide exposed infants received hydrocortisone 3 days later than surfactant only infants (median DOL 5 vs. 2, p < 0.001). Infants receiving budesonide had higher blood pressures, required less dopamine (19% vs. 39%, p < 0.001) and dobutamine (2% vs. 6%, p = 0.02). Budesonide exposed infants were discharged home after a shorter NICU stay (85 days vs. 94 days, p = 0.02) and at a younger gestational age (39 vs. 40 weeks, p = 0.001). CONCLUSIONS: The use of surfactant and budesonide does not alter the rate of hydrocortisone use, but does delay the timing of treatment initiation and decreases the use of vasoactive medications.

Skin tone preferences and their influence on skin care behaviors.

Knowledge regarding skin tone preferences and their influence on skincare behaviors among people of color is limited. The objective of this study was to determine whether there is a difference between ideal and actual skin tone among people of color and whether this difference is associated with tanning and sunscreen use. This was a one-time, voluntary, anonymous, electronic survey designed in REDCap and delivered through ResearchMatch, a national electronic, recruitment tool. Eligible participants were at least 18 years old and self-identified as Black, Asian, Latinx, American Indian/Alaskan Native or Mixed Race. In total, 548 completed survey results were analyzed using SAS. Only the Latinx population was found to have a significant preference for tanner skin (p < 0.05). The Latinx population had significantly more subjects that participated in outdoor tanning than both the Black (p < 0.0001) and Asian population (p < 0.05). Latinx participants who indicated a preference for tanner skin were 2.8 times more likely to never use sunscreen than those without this preference (OR = 2.821, CI = 1.029-7.732, p < 0.05). Our findings have implications for how dermatologists screen, treat, and educate Latinx and skin of color populations.

A Pilot Study Assessing Aspects of Sexual Function Predicted to Be Important After Treatment for Prostate Cancer in Gay Men: An Underserved Domain Highlighted.

Purpose: Existing questionnaires assessing sexual function after prostate cancer (PCa) were developed in predominantly heterosexual male cohorts and may measure function incompletely in gay men. We sought to determine if there are sexual function domains relevant to gay men that are not captured by the Expanded Prostate Cancer Index Composite (EPIC) sexual function assessment. Methods: Fifty-three gay men with PCa responded to an online survey regarding the applicability of the sexual function domain in the validated EPIC questionnaire. They were then queried about whether the prostate is a source of sexual pleasure and the importance of measuring sexual satisfaction as it relates to receptive anal intercourse. Results: A majority of gay men with PCa found the EPIC sexual function tool to be applicable when measuring erectile function (76.5%). Of the men queried, 64.2% felt that the prostate is a source of sexual pleasure and 52.8% felt it important to measure sexual satisfaction associated with receptive anal intercourse. A larger proportion of gay men who engaged in receptive anal intercourse, compared with those who did not engage in receptive anal intercourse, felt that the prostate is a source of sexual pleasure (100% vs. 57.1%), and thought it important to measure sexual satisfaction as it relates to receptive anal intercourse after PCa treatment (90.0% vs. 45.2%). Conclusions: Our findings highlight the need to create a validated questionnaire to measure sexual satisfaction from receptive anal intercourse to help care for men engaging in receptive anal intercourse after PCa treatment.

Estrogen receptor-α in female skeletal muscle is not required for regulation of muscle insulin sensitivity and mitochondrial regulation.

OBJECTIVE: Estrogen receptor-α (ERα) is a nuclear receptor family member thought to substantially contribute to the metabolic regulation of skeletal muscle. However, previous mouse models utilized to assess the necessity of ERα signaling in skeletal muscle were confounded by altered developmental programming and/or influenced by secondary effects, making it difficult to assign a causal role for ERα. The objective of this study was to determine the role of skeletal muscle ERα in regulating metabolism in the absence of confounding factors of development. METHODS: A novel mouse model was developed allowing for induced deletion of ERα in adult female skeletal muscle (ERαKOism). ERαshRNA was also used to knockdown ERα (ERαKD) in human myotubes cultured from primary human skeletal muscle cells isolated from muscle biopsies from healthy and obese insulin-resistant women. RESULTS: Twelve weeks of HFD exposure had no differential effects on body composition, VO2, VCO2, RER, energy expenditure, and activity counts across genotypes. Although ERαKOism mice exhibited greater glucose intolerance than wild-type (WT) mice after chronic HFD, ex vivo skeletal muscle glucose uptake was not impaired in the ERαKOism mice. Expression of pro-inflammatory genes was altered in the skeletal muscle of the ERαKOism, but the concentrations of these inflammatory markers in the systemic circulation were either lower or remained similar to the WT mice. Finally, skeletal muscle mitochondrial respiratory capacity, oxidative phosphorylation efficiency, and H2O2 emission potential was not affected in the ERαKOism mice. ERαKD in human skeletal muscle cells neither altered differentiation capacity nor caused severe deficits in mitochondrial respiratory capacity. CONCLUSIONS: Collectively, these results suggest that ERα function is superfluous in protecting against HFD-induced skeletal muscle metabolic derangements after postnatal development is complete.

Using Electronic Health Records to Measure Quality Improvement Efforts: Findings from a Large Practice Facilitation Initiative.

BACKGROUND: Federal incentives for electronic health record (EHR) use typically require quality measure reporting over calendar year or 90-day periods. However, required reporting periods may not align with time frames of real-world quality improvement (QI) efforts. This study described primary care practices' ability to obtain measures with reporting periods aligning with a large QI initiative. METHODS: Researchers conducted a substudy of a randomized trial testing practice facilitation strategies for preventive cardiovascular care. Three quality measures (aspirin for ischemic vascular disease; blood pressure control for hypertension; smoking screening/cessation) were collected quarterly over one year. The primary outcome was a binary indicator of whether a practice facilitator obtained all three measures with "rolling 12-month" reporting periods (that is, the year preceding each study quarter). RESULTS: The study included 107 practices, 63 (58.9%) of which met the primary outcome of obtaining all measures with rolling 12-month reporting periods. Smaller practices were less likely to meet the primary outcome (p < 0.001). Practices used 11 different EHRs, 3 of which were unable to consistently produce rolling 12-month measures; at 33 practices (30.8%) using these 3 EHRs, facilitators met a secondary outcome of obtaining prior calendar year and rolling 3-month measures. Facilitators reported barriers to data collection such as practices lacking optional EHR features, and EHRs' inability to produce reporting periods across two calendar years. CONCLUSION: EHR vendors' compliance with federal reporting requirements is not necessarily sufficient to support real-world QI work. Improvements are needed in the flexibility and usability of EHRs' quality measurement functions, particularly for smaller practices.

A Trans-Ethnic Genome-Wide Association Study of Uterine Fibroids.

Uterine fibroids affect up to 77% of women by menopause and account for up to $34 billion in healthcare costs each year. Although fibroid risk is heritable, genetic risk for fibroids is not well understood. We conducted a two-stage case-control meta-analysis of genetic variants in European and African ancestry women with and without fibroids classified by a previously published algorithm requiring pelvic imaging or confirmed diagnosis. Women from seven electronic Medical Records and Genomics (eMERGE) network sites (3,704 imaging-confirmed cases and 5,591 imaging-confirmed controls) and women of African and European ancestry from UK Biobank (UKB, 5,772 cases and 61,457 controls) were included in the discovery genome-wide association study (GWAS) meta-analysis. Variants showing evidence of association in Stage I GWAS (P < 1 × 10-5) were targeted in an independent replication sample of African and European ancestry individuals from the UKB (Stage II) (12,358 cases and 138,477 controls). Logistic regression models were fit with genetic markers imputed to a 1000 Genomes reference and adjusted for principal components for each race- and site-specific dataset, followed by fixed-effects meta-analysis. Final analysis with 21,804 cases and 205,525 controls identified 326 genome-wide significant variants in 11 loci, with three novel loci at chromosome 1q24 (sentinel-SNP rs14361789; P = 4.7 × 10-8), chromosome 16q12.1 (sentinel-SNP rs4785384; P = 1.5 × 10-9) and chromosome 20q13.1 (sentinel-SNP rs6094982; P = 2.6 × 10-8). Our statistically significant findings further support previously reported loci including SNPs near WT1, TNRC6B, SYNE1, BET1L, and CDC42/WNT4. We report evidence of ancestry-specific findings for sentinel-SNP rs10917151 in the CDC42/WNT4 locus (P = 1.76 × 10-24). Ancestry-specific effect-estimates for rs10917151 were in opposite directions (P-Het-between-groups = 0.04) for predominantly African (OR = 0.84) and predominantly European women (OR = 1.16). Genetically-predicted gene expression of several genes including LUZP1 in vagina (P = 4.6 × 10-8), OBFC1 in esophageal mucosa (P = 8.7 × 10-8), NUDT13 in multiple tissues including subcutaneous adipose tissue (P = 3.3 × 10-6), and HEATR3 in skeletal muscle tissue (P = 5.8 × 10-6) were associated with fibroids. The finding for HEATR3 was supported by SNP-based summary Mendelian randomization analysis. Our study suggests that fibroid risk variants act through regulatory mechanisms affecting gene expression and are comprised of alleles that are both ancestry-specific and shared across continental ancestries.

Evaluation of pharmacokinetic/pharmacodynamic and clinical outcomes with 6-hourly empiric piperacillin-tazobactam dosing in hematological malignancy patients with febrile neutropenia.

BACKGROUND: Piperacillin-tazobactam is commonly used in neutropenic sepsis at standard doses that do not account for inter-individual differences in age, bodyweight and renal function. This study was designed to assess the rate of attainment of pharmacokinetic/pharmacodynamic (PK/PD) targets in patients receiving piperacillin/tazobactam therapy and to evaluate the effect on clinical outcomes. METHODS: Patients undergoing intensive chemotherapy for aggressive hematological malignancies were enrolled and treated with piperacillin/tazobactam 4 g/0.5 g every 6 h as initial antimicrobial therapy for first fever. Plasma drug concentrations were assayed at 50% and 100% of the dosing interval and compared with target MIC breakpoint of 16 mg/L to calculate the primary endpoints of 50% and 100% time above MIC (fT > MIC), respectively. Secondary endpoints included time to clinical cure, length of hospital stay, duration of antibiotics, and clinical treatment success. RESULTS: Fifty-eight percent (14/24) of patients achieved 50% fT > MIC while only 4% (1/24) achieved 100% fT > MIC. Higher creatinine clearance was significantly associated with lower trough drug concentration and appeared to be the dominant reason for the poor PK/PD target attainment. Median time to clinical cure, duration of antibiotic therapy, and hospital length of stay was 3, 13 and 21 days, respectively. There were no statistically significant differences in these outcomes between patients who did and did not achieve 100% fT > MIC. CONCLUSIONS: A significant majority of febrile neutropenic patients fail to achieve PK/PD targets with 6-hourly piperacillin dosing, although the clinical implications of this finding are unclear. Larger studies are needed to assess any impact on morbidity and mortality. This trial is registered on the ANZCTR (ACTRN12618000110280).

Induced in vivo knockdown of the Brca1 gene in skeletal muscle results in skeletal muscle weakness.

KEY POINTS: Breast cancer 1 early onset gene codes for the DNA repair enzyme, breast cancer type 1 susceptibility protein (BRCA1). The gene is prone to mutations that cause a loss of protein function. BRCA1/Brca1 has recently been found to regulate several cellular pathways beyond DNA repair and is expressed in skeletal muscle. Skeletal muscle specific knockout of Brca1 in mice caused a loss of muscle quality, identifiable by reductions in muscle force production and mitochondrial respiratory capacity. Loss of muscle quality was associated with a shift in muscle phenotype and an accumulation of mitochondrial DNA mutations. These results demonstrate that BRCA1 is necessary for skeletal muscle function and that increased mitochondrial DNA mutations may represent a potential underlying mechanism. ABSTRACT: Recent evidence suggests that the breast cancer 1 early onset gene (BRCA1) influences numerous peripheral tissues, including skeletal muscle. The present study aimed to determine whether induced-loss of the breast cancer type 1 susceptibility protein (Brca1) alters skeletal muscle function. We induced genetic ablation of exon 11 in the Brca1 gene specifically in the skeletal muscle of adult mice to generate skeletal muscle-specific Brca1 homozygote knockout (Brca1KOsmi ) mice. Brca1KOsmi exhibited kyphosis and decreased maximal isometric force in limb muscles compared to age-matched wild-type mice. Brca1KOsmi skeletal muscle shifted toward an oxidative muscle fibre type and, in parallel, increased myofibre size and reduced capillary numbers. Unexpectedly, myofibre bundle mitochondrial respiration was reduced, whereas contraction-induced lactate production was elevated in Brca1KOsmi muscle. Brca1KOsmi mice accumulated mitochondrial DNA mutations and exhibited an altered mitochondrial morphology characterized by distorted and enlarged mitochondria, and these were more susceptible to swelling. In summary, skeletal muscle-specific loss of Brca1 leads to a myopathy and mitochondriopathy characterized by reductions in skeletal muscle quality and a consequent kyphosis. Given the substantial impact of BRCA1 mutations on cancer development risk in humans, a parallel loss of BRCA1 function in patient skeletal muscle cells would potentially result in implications for human health.

A case study evaluating the portability of an executable computable phenotype algorithm across multiple institutions and electronic health record environments.

Electronic health record (EHR) algorithms for defining patient cohorts are commonly shared as free-text descriptions that require human intervention both to interpret and implement. We developed the Phenotype Execution and Modeling Architecture (PhEMA, http://projectphema.org) to author and execute standardized computable phenotype algorithms. With PhEMA, we converted an algorithm for benign prostatic hyperplasia, developed for the electronic Medical Records and Genomics network (eMERGE), into a standards-based computable format. Eight sites (7 within eMERGE) received the computable algorithm, and 6 successfully executed it against local data warehouses and/or i2b2 instances. Blinded random chart review of cases selected by the computable algorithm shows PPV ≥90%, and 3 out of 5 sites had >90% overlap of selected cases when comparing the computable algorithm to their original eMERGE implementation. This case study demonstrates potential use of PhEMA computable representations to automate phenotyping across different EHR systems, but also highlights some ongoing challenges.

Design of healthy hearts in the heartland (H3): A practice-randomized, comparative effectiveness study.

BACKGROUND: The Healthy Hearts in the Heartland (H3) study is part of a nationwide effort, EvidenceNOW, seeking to better understand the ability of small primary care practices to improve "ABCS" clinical quality measures: appropriate Aspirin therapy, Blood pressure control, Cholesterol management, and Smoking cessation. H3 aimed to assess feasibility of implementing Point-of-Care (POC) or POC plus Population Management (POC + PM) quality improvement (QI) strategies to improve ABCS at practices in Illinois, Indiana, and Wisconsin. We describe the design and randomization of the H3 study. METHODS: We conducted a two-arm (1:1, POC:POC + PM), practice-randomized, comparative effectiveness study in 226 primary care practices across four "waves" of randomization with a 12-month intervention period, followed by a six-month sustainability period. Randomization controlled imbalance in nine baseline variables through a modified constrained algorithm. Among others, we used initial, unverified estimates of baseline ABCS values. RESULTS: We randomized 112 and 114 practices to POC and POC + PM arms, respectively. Randomization ensured baseline comparability for all nine key variables, including the ABCS measures indicating proportion of patients at the practice level meeting each quality measure. Median(Inner Quartile Range) values were A: 0.78(0.66-0.86) in POC arm vs. 0.77(0.63-0.86) in POC + PM arm, B: 0.64(0.53-0.73) vs. 0.64(0.53-0.75), C: 0.78(0.63-0.86) vs. 0.75(0.64-0.81), S: 0.80(0.65-0.81) vs. 0.79(0.61-0.91). DISCUSSION: Surrogate estimates for the true ABCS at baseline coupled with the unique randomization logic achieved adequate baseline balance on these outcomes. Similar practice- or cluster-randomized trials may consider adaptations of this design. Final analyses on 12- and 18-month ABCS outcomes for the H3 study are forthcoming. TRIAL REGISTRATION: This trial is registered on ClinicalTrials.gov (Initial post: 11/05/2015; identifier: NCT02598284; https://clinicaltrials.gov/ct2/show/NCT02598284?term=NCT02598284&rank=1).

Induced Cre-mediated knockdown of Brca1 in skeletal muscle reduces mitochondrial respiration and prevents glucose intolerance in adult mice on a high-fat diet.

The breast cancer type 1 susceptibility protein (Brca1) is a regulator of DNA repair in mammary gland cells; however, recent cell culture evidence suggests that Brca1 influences other processes, including those in nonmammary cells. In this study, we sought to determine whether Brca1 is necessary for metabolic regulation of skeletal muscle using a novel in vivo mouse model. We developed an inducible skeletal muscle-specific Brca1knockout (BRCA1KOsmi) model to test whether Brca1 expression is necessary for maintenance of metabolic function of skeletal muscle when exposed to a high-fat diet (HFD). Our data demonstrated that deletion of Brca1 prevented HFD-induced alterations in glucose and insulin tolerance. Irrespective of diet, BRCA1KOsmi mice exhibited significantly lower ADP-stimulated complex I mitochondrial respiration rates compared to age-matched wild-type (WT) mice. The data show that Brca1 has the ability to localize to the mitochondria in skeletal muscle and that BRCA1KOsmi mice exhibit higher whole-body CO2 production, respiratory exchange ratio, and energy expenditure, compared with the WT mice. Our results demonstrate that loss of Brca1 in skeletal muscle leads to dysregulated metabolic function, characterized by decreased mitochondrial respiration. Thus, any condition that results in loss of Brca1 function could induce metabolic imbalance in skeletal muscle.-Jackson, K. C., Tarpey, M. D., Valencia, A. P., Iñigo, M. R., Pratt, S. J., Patteson, D. J., McClung, J. M., Lovering, R. M., Thomson, D. M., Spangenburg, E. E. Induced Cre-mediated knockdown of Brca1 in skeletal muscle reduces mitochondrial respiration and prevents glucose intolerance in adult mice on a high-fat diet.

A Comparison of High-Dose Cytarabine During Induction Versus Consolidation Therapy in Newly Diagnosed AML.

The proportion of patients with acute myeloid leukemia (AML) cured is increased by administering high-dose cytarabine (HiDAC). It remains uncertain whether to administer HiDAC as induction or consolidation, and whether ≥1 cycle of HiDAC is required. Our retrospective study of 416 adult AML patients, excluding good risk cytogenetics, compared a single cycle of HiDAC-based therapy followed by 2 cycles of standard-dose cytarabine (SDAC) (HiDAC induction cohort) with SDAC-based chemotherapy followed by 2 cycles of HiDAC-based chemotherapy (HiDAC consolidation cohort). Complete remission (CR) rate was greater in the HiDAC induction cohort (90% vs 78%, P < 0.01) which did not lead to an improved overall survival (48% vs 43%, P = 0.18) or disease-free survival (DFS) (39% vs 45%, P = 0.95). We noted that, after censoring for allogeneic hematopoetic stem cell transplant (alloHSCT) in CR1, the cumulative incidence of relapse was lower in the HiDAC consolidation cohort in patients with intermediate risk cytogenetics (68% vs 44%, P = 0.01), which lead to a greater DFS (30% vs 47%, P = 0.095). In the patients with adverse risk cytogenetics, the RR was numerically greater in the HiDAC consolidation cohort (52% vs 80%, P = 0.60) which lead to a lower DFS (27% vs 4%, P = 0.11). Our data show that, although the HiDAC induction cohort (1 cycle of HiDAC) achieved a greater CR rate, there were no overall survival differences between the 2 cohorts, and that the HiDAC consolidation cohort (2 cycles of HiDAC) had a lower RR and greater DFS in those patients with intermediate risk cytogenetics who did not undergo alloHSCT in CR1.

Does the presence of cardiovascular disease risk factors or established disease influence the dietary intake of affected adults and their children residing in the same household? A secondary analysis of the Australian Health Survey (2011-2013).

BACKGROUND: Diet is an important contributor to risk of cardiovascular disease (CVD) and integral in management and delaying progression. Little is known however about whether increased CVD risk or established CVD has any influence on dietary intakes of Australian adults or children residing in the same household. This study aimed to determine whether the presence of CVD or CVD risk factors influences dietary intake of Australian adults and if the presence of an adult with increased CVD risk influences the dietary intake of a child living in the same household. METHODS: Data were sourced from the 2011-2013 Australian Health Survey for: (1) adults ≥18 years with risk factors or established CVD and (2) children 2-17 years residing in the same household as adults with CVD risk factors or established CVD. Selected nutrient intakes (total fat, saturated fat plus trans fat, alpha-linolenic acid, total long chain omega 3 fatty acids, fibre and sodium) collected by repeated 24 h recalls were compared to national dietary recommendations and to the intakes of all other adults and children surveyed. Standard errors of the estimates were calculated using the replicate weights method, and an alpha value of <0.05 considered statistically significant. RESULTS: Six thousand two hundred sixty five of 9435 adults surveyed were identified as having CVD risk factors or established disease and of these 1609 had a child in the same household that also contributed data in this survey. No differences were observed in adjusted mean dietary intakes between those without risk factors or established CVD and those with, except for total energy and sodium which were significantly lower in the adults with CVD risk factors and/or established disease. However sodium intakes across both groups were higher than recommended targets. There were no differences for selected nutrients between children residing with affected adults and other children surveyed. CONCLUSIONS: While intakes of Australian adults with CVD risk factors or established disease were favourable for sodium, compared to unaffected adults, there is still scope for improvement as many Australian adults, despite CVD risk, are unable to achieve targets for selected nutrients. Effective dietary behaviour change strategies and resources are urgently needed.

Psychometric evaluation and design of patient-centered communication measures for cancer care settings.

OBJECTIVE: To evaluate the psychometric properties of questions that assess patient perceptions of patient-provider communication and design measures of patient-centered communication (PCC). METHODS: Participants (adults with colon or rectal cancer living in North Carolina) completed a survey at 2 to 3 months post-diagnosis. The survey included 87 questions in six PCC Functions: Exchanging Information, Fostering Health Relationships, Making Decisions, Responding to Emotions, Enabling Patient Self-Management, and Managing Uncertainty. For each Function we conducted factor analyses, item response theory modeling, and tests for differential item functioning, and assessed reliability and construct validity. RESULTS: Participants included 501 respondents; 46% had a high school education or less. Reliability within each Function ranged from 0.90 to 0.96. The PCC-Ca-36 (36-question survey; reliability=0.94) and PCC-Ca-6 (6-question survey; reliability=0.92) measures differentiated between individuals with poor and good health (i.e., known-groups validity) and were highly correlated with the HINTS communication scale (i.e., convergent validity). CONCLUSION: This study provides theory-grounded PCC measures found to be reliable and valid in colorectal cancer patients in North Carolina. Future work should evaluate measure validity over time and in other cancer populations. PRACTICE IMPLICATIONS: The PCC-Ca-36 and PCC-Ca-6 measures may be used for surveillance, intervention research, and quality improvement initiatives.

Distance from hospital impacts adverse event detection after outpatient endoscopy.

BACKGROUND AND AIMS: Monitoring adverse events (AEs) after GI endoscopy is an endorsed quality measure but is challenging to implement in practice. Patients with major AEs may seek care elsewhere after endoscopy. We aimed to determine the hospital utilization patterns of patients with AEs after ambulatory endoscopy. METHODS: We used the HealthLNK Data Repository, which uses a software application for integration of deidentified, patient-level clinical data across institutions. Data for patients undergoing outpatient endoscopy from 2010 to 2011 at 5 Chicago-area hospitals were used. Early mortality was defined as death no more than 2 months after the outpatient procedure. AEs were defined as a hospital admission for perforation, bleeding, or pancreatitis the same or following month after endoscopy. RESULTS: During the study period, 42,842 outpatient procedures were performed in 22,898 unique individuals. Early mortality occurred in 86 patients (.4%). Per-patient mortality was greatest after outpatient ERCP (2.5%, P < .0001). Of 86 patients with early mortality, 36 (42%) were not hospitalized at the index hospital after endoscopy. Patients who did not return to the index hospital lived farther from the index hospital (P = .02). In total, 8.3% of ambulatory endoscopies were associated with potential endoscopy-related AEs. The observed rate of potential AEs trended downward as patients' home zip codes moved farther from the index hospital (P = .01). CONCLUSIONS: Nearly half of patients who die soon after outpatient endoscopy are not hospitalized at their index hospital after endoscopy. The observed AE rate was higher for patients living closer to the index hospital, suggesting that patients who live farther away are less likely to return to the index hospital for emergency care. Novel methods to efficiently track outcomes after outpatient endoscopy are needed.