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PurposeThe benefit of using the Zilver PTX drug-eluting stent (DES) in superficial femoral artery (SFA) lesions has been demonstrated in multiple clinical studies. This prospective, multicenter study evaluated the 1-year safety and effectiveness of the DES for the treatment of femoropopliteal lesions in a Chinese patient population.MethodsPatients with a single de novo or restenotic SFA lesion ≤140 mm and a Rutherford classification of 2 to 4 were treated with the DES. The primary endpoint was primary patency assessed by duplex ultrasound at 1-year. Secondary endpoints included adverse events, event-free survival (EFS), and freedom from target lesion revascularization (TLR). Clinical outcomes included Rutherford classification, ankle-brachial index (ABI), and the walking impairment questionnaire (WIQ).ResultsIn this study, 178 patients with symptomatic peripheral artery disease were enrolled at nine institutions in China. The average lesion length was 79.0 ± 48.6 mm (range 14.8–245.4 mm) and 50.0% of lesions were total occlusions. The 1-year primary patency rate was 81.9%. Covariate analysis revealed that lesion length (p < 0.01) was the only significant factor for patency. No paclitaxel-related adverse events or amputations were reported. The 1-year rate for EFS was 94.9% and freedom from TLR was 95.5%. Through 1-year, treatment with the DES resulted in statistically significant improvement in ABI and WIQ scores compared with pre-procedure (p < 0.001). Clinical improvement of at least 1 Rutherford class was achieved in 142 of 174 patients (81.6%).ConclusionThis study showed promising short-term results for the treatment of SFA lesions with Zilver PTX DES in Chinese patients.Unique identifierClinicalTrials.gov, identifier: NCT02171962.

Background: We are facing an ongoing pandemic of coronavirus disease 2019 (COVID-19), which is causing detrimental effects on mental health, including disturbing consequences on child maltreatment and intimate partner violence., Methods: We sought to identify predictors of child maltreatment and intimate partner violence from 380 participants (mean age 36.67 ± 10.61, 63.2% male; Time 3: June 2020) using modern machine learning analysis (random forest and SHAP values). We predicted that COVID-related factors (such as days in lockdown), parents' psychological distress during the pandemic (anxiety, depression), their personality traits, and their intimate partner relationship will be key contributors to child maltreatment. We also examined if there is an increase in family violence during the pandemic by using an additional cohort at two time points (Time 1: March 2020, N = 434; mean age 35.67 ± 9.85, 41.69% male; and Time 2: April 2020, N = 515; mean age 35.3 ± 9.5, 34.33%)., Results: Feature importance analysis revealed that parents' affective empathy, psychological well-being, outdoor activities with children as well as a reduction in physical fights between partners are strong predictors of a reduced risk of child maltreatment. We also found a significant increase in physical punishment (Time 3: 66.26%) toward children, as well as in physical (Time 3: 36.24%) and verbal fights (Time 3: 41.08%) among partners between different times., Conclusion: Using modernized predictive algorithms, we present a spectrum of features that can have influential weight on prediction of child maltreatment. Increasing awareness about family violence consequences and promoting parenting programs centered around mental health are imperative., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Todorovic, O’Leary, Ward, Devarasetty, Lee, Knox and Andari.)

Objectives: Routine preoperative axial imaging studies (CT/MRI) are not recommended for endometrioid endometrial cancer as they are unlikely to change management and may delay surgery. This study evaluated the association of receiving preoperative imaging on various outcomes., Methods: A population-based cohort of Endometrioid Endometrial Cancer cases from 2006 to 2016 were identified from the Cancer Registry in Ontario, Canada. Wait time to surgery, type of surgery and overall survival were evaluated in patients with and without preoperative imaging. Predictive factors for wait time > 56 days and aggressive surgery (radical hysterectomy / lymphadenectomy) were determined using multivariable regression analysis., Results: 13,050 cases were included. 22.6% of patients received preoperative imaging, mainly CT scans. Most patients (95.9%) received no neoadjuvant treatment. Patients with preoperative imaging were more likely to have neoadjuvant treatment (11.7% vs. 1.8%) and less likely to have surgery at 180 days post diagnosis (87.9% vs 94.6%). Patients with preoperative imaging had median wait time to surgery of 64 days (47-87), compared to 53 days (36-74) than those without imaging (p < 0.001). Multivariable modeling showed preoperative imaging was associated with decreased odds of having surgery within 56 days (OR = 0.68, 95% CI = 0.62-0.75), and increased odds (OR = 1.73, 95% CI = 1.53-1.95) of having aggressive surgery. The 5-year overall survival for patients with imaging was 84.8% versus 91.1% for patients without preoperative imaging., Conclusions: Preoperative imaging was associated with longer wait times to surgery, more aggressive surgery, surgery with a gynecologic oncologist and increased use of neoadjuvant and adjuvant treatment. In early-stage disease there was no observed improvement in overall survival for patients with preoperative imaging. Further research on potential benefits of preoperative imaging in higher risk patients is required., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To compare recent immigrants and long-term residents in Ontario, Canada, on established health service quality indicators of end-of-life cancer care., Design: Retrospective, population-based cohort study of cancer decedents between 2004 and 2015., Setting: Ontario, Canada., Participants: We grouped 13 085 immigrants who arrived in Ontario in 1985 or later into eight major ethnic groups based on birth country, mother tongue and surname, and compared them to 229 471 long-term residents who were ≥18 years at the time of death., Primary and Secondary Outcome Measures: Aggressive care, defined as a composite of ≥2 emergency department visits, ≥2 new hospitalisations or an intensive care unit admission within 30 days of death; and supportive care, defined as a physician house call within 2 weeks, or palliative nursing or personal support worker home visit within 6 months of death. Multivariable logistic regression was used to examine the association between immigration status and the odds of each main outcome., Results: Compared with long-term residents, immigrants overall and by ethnic group had higher rates of aggressive care (13.7% vs 17.5%, respectively; p<0.001). Among immigrants, Southeast Asians had the highest use while White-Eastern and Western Europeans had the lowest. Supportive care use was similar between long-term residents and immigrants (50.0% vs 50.5%, respectively; p=0.36), though lower among Southeast Asians (46.6%) and higher among White-Western Europeans (55.6%). After adjusting for sociodemographic characteristics and comorbidities, immigrants remained more likely than long-term residents to receive aggressive care (OR: 1.15, 95% CI 1.09 to 1.21), yet were less likely to receive supportive care (OR: 0.95, 95% CI 0.91 to 0.98)., Conclusions: Among cancer decedents in Ontario, immigrants are more likely to use aggressive healthcare services at the end of life than long-term residents, while supportive care varies by ethnicity. Contributors to variation in end-of-life care require further study., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In the 2011 US hospital prevalence survey of healthcare-associated infections and antimicrobial use 50% of patients received antimicrobial medications on the survey date or day before. More hospitals have since established antimicrobial stewardship programs. We repeated the survey in 2015 to determine antimicrobial use prevalence and describe changes since 2011., Methods: The Centers for Disease Control and Prevention's Emerging Infections Program sites in 10 states each recruited ≤25 general and women's and children's hospitals. Hospitals selected a survey date from May-September 2015. Medical records for a random patient sample on the survey date were reviewed to collect data on antimicrobial medications administered on the survey date or day before. Percentages of patients on antimicrobial medications were compared; multivariable log-binomial regression modeling was used to evaluate factors associated with antimicrobial use., Results: Of 12 299 patients in 199 hospitals, 6084 (49.5%; 95% CI, 48.6-50.4%) received antimicrobials. Among 148 hospitals in both surveys, overall antimicrobial use prevalence was similar in 2011 and 2015, although the percentage of neonatal critical care patients on antimicrobials was lower in 2015 (22.8% vs 32.0% [2011]; P = .006). Fluoroquinolone use was lower in 2015 (10.1% of patients vs 11.9% [2011]; P < .001). Third- or fourth-generation cephalosporin use was higher (12.2% vs 10.7% [2011]; P = .002), as was carbapenem use (3.7% vs 2.7% [2011]; P < .001)., Conclusions: Overall hospital antimicrobial use prevalence was not different in 2011 and 2015; however, differences observed in selected patient or antimicrobial groups may provide evidence of stewardship impact., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Objectives: Clinical practice guidelines recommend against routine preoperative axial imaging studies (CT/MRI) for endometrial cancer, except for cases of locally advanced disease or aggressive histologies. This study utilized population-based data to evaluate the use of preoperative imaging and factors associated with its use., Methods: A population-based cohort of women diagnosed with endometrial cancer from 2006 to 2016 were identified from the Ontario Cancer Registry in Ontario, Canada. Patients were excluded if they had: hysterectomy prior to the date of diagnosis, non-epithelial histology or a prior cancer diagnosis within 5 years. Preoperative imaging (CT or MRI) rates were calculated over time. Predictive factors for preoperative imaging use were determined using multi-variable regression analysis., Results: 17,718 cases were eligible for analysis. From 2006 to 2016, the proportion of patients receiving preoperative imaging increased from 22.2% to 39.3%. In a subgroup of patients with low-risk disease (stage 1, endometrioid adenocarcinoma), imaging increased from 16.3% to 29.5%. Multivariate analysis showed an association between preoperative imaging and advanced stage, advanced grade, non-endometrioid morphology, surgery with a gynecologic oncologist, surgery at a teaching hospital and a later year of diagnosis. From 2006 to 2016, the yearly incidence of endometrial cancer increased from 22.3/100,000 to 36.1/100,000, representing a mean annual increase of 3.6% per year., Conclusions: Endometrial cancer incidence and the use of preoperative imaging are increasing. Factors most associated with preoperative imaging are high-risk features. However, preoperative imaging is still being performed in low-risk patients, indicating non-adherence to guidelines, which has implications for constrained healthcare resources., Competing Interests: Declaration of Competing Interest There were no conflicts of interest to disclose., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Importance: Hospital antimicrobial consumption data are widely available; however, large-scale assessments of the quality of antimicrobial use in US hospitals are limited., Objective: To evaluate the appropriateness of antimicrobial use for hospitalized patients treated for community-acquired pneumonia (CAP) or urinary tract infection (UTI) present at admission or for patients who had received fluoroquinolone or intravenous vancomycin treatment., Design, Setting, and Participants: This cross-sectional study included data from a prevalence survey of hospitalized patients in 10 Emerging Infections Program sites. Random samples of inpatients on hospital survey dates from May 1 to September 30, 2015, were identified. Medical record data were collected for eligible patients with 1 or more of 4 treatment events (CAP, UTI, fluoroquinolone treatment, or vancomycin treatment), which were selected on the basis of common infection types reported and antimicrobials given to patients in the prevalence survey. Data were analyzed from August 1, 2017, to May 31, 2020., Exposure: Antimicrobial treatment for CAP or UTI or with fluoroquinolones or vancomycin., Main Outcomes and Measures: The percentage of antimicrobial use that was supported by medical record data (including infection signs and symptoms, microbiology test results, and antimicrobial treatment duration) or for which some aspect of use was unsupported. Unsupported antimicrobial use was defined as (1) use of antimicrobials to which the pathogen was not susceptible, use in the absence of documented infection signs or symptoms, or use without supporting microbiologic data; (2) use of antimicrobials that deviated from recommended guidelines; or (3) use that exceeded the recommended duration., Results: Of 12 299 patients, 1566 patients (12.7%) in 192 hospitals were included; the median age was 67 years (interquartile range, 53-79 years), and 864 (55.2%) were female. A total of 219 patients (14.0%) were included in the CAP analysis, 452 (28.9%) in the UTI analysis, 550 (35.1%) in the fluoroquinolone analysis, and 403 (25.7%) in the vancomycin analysis; 58 patients (3.7%) were included in both fluoroquinolone and vancomycin analyses. Overall, treatment was unsupported for 876 of 1566 patients (55.9%; 95% CI, 53.5%-58.4%): 110 of 403 (27.3%) who received vancomycin, 256 of 550 (46.6%) who received fluoroquinolones, 347 of 452 (76.8%) with a diagnosis of UTI, and 174 of 219 (79.5%) with a diagnosis of CAP. Among patients with unsupported treatment, common reasons included excessive duration (103 of 174 patients with CAP [59.2%]) and lack of documented infection signs or symptoms (174 of 347 patients with UTI [50.1%])., Conclusions and Relevance: The findings suggest that standardized assessments of hospital antimicrobial prescribing quality can be used to estimate the appropriateness of antimicrobial use in large groups of hospitals. These assessments, performed over time, may inform evaluations of the effects of antimicrobial stewardship initiatives nationally.

Importance: Prostate cancer is the third leading cause of cancer-related death in men in the United States. Although serious, most of these diagnoses are not terminal. Inherited risk for prostate cancer is associated with aggressive disease and poorer outcomes, indicating a critical need for increased genetic screening to identify disease-causing variants that can pinpoint individuals at increased risk for metastatic castration-resistant prostate cancer., Objective: To identify positive (pathogenic, likely pathogenic, and increased risk) germline variants in a large prostate cancer cohort and to evaluate the usefulness of current practice guidelines in recognizing individuals at increased risk for prostate cancer who would benefit from diagnostic genetic testing., Design, Setting, and Participants: Cross-sectional study of data from 3607 men with a personal history of prostate cancer who underwent germline genetic testing between 2013 and 2018 and were unselected for family history, stage of disease, or age at diagnosis. Referral-based testing was performed at a Clinical Laboratory Improvement Amendments/College of American Pathologists-certified diagnostic laboratory. All analysis took place between February 2017 and August 2018., Main Outcomes and Measures: The frequency and distribution of positive germline variants, and the percentage of individuals with prostate cancer who met National Comprehensive Cancer Network (NCCN) guidelines for germline genetic testing., Results: Of 3607 men (mean [SD] age at testing, 67 [9.51] years; mean age at diagnosis, 60 [9.05] years) with a personal diagnosis of prostate cancer who were referred for genetic testing, 620 (17.2%) had positive germline variants, of which only 30.7% were variants in BRCA1/2. Positive variants in HOXB13, a gene associated only with prostate cancer risk, were identified in 30 patients (4.5%). DNA mismatch repair variants with substantial known therapeutic implications were detected in 1.74% of variants in the total population tested. Examination of self-reported family histories indicated that 229 individuals (37%) with positive variants in this cohort would not have been approved for genetic testing using the NCCN genetic/familial breast and ovarian guidelines for patients with prostate cancer., Conclusions and Relevance: Current NCCN guidelines and Gleason scores cannot reliably stratify patients with prostate cancer for the presence or absence of pathogenic germline variants. Most positive genetic test results identified in this study have important management implications for patients and their families, which underscores the need to revisit current guidelines.

Background: Genetic testing capability and guidelines are rapidly expanding to assess inherited prostate cancer (PCA). Clinical genetic data from multigene testing can provide insights into the germline pathogenic variant (PV) spectrum and correlates in men with PCA unselected for metastatic disease to optimize identification of men for genetic evaluation and management., Methods: A retrospective cross-sectional analysis was conducted of de-identified clinical genetic testing data from a large commercial genetic testing laboratory in the US. ICD-10 claims codes were used to identify men with PCA, along with family history data. Gleason score was abstracted from test request forms. Overall PV rate among men with PCA was estimated, along with PVs in DNA repair genes. Family history and Gleason score association to germline DNA repair PVs was assessed using Fisher's exact test with correction for false-discovery., Results: As of August 2017, genetic results were available on 1328 men with PCA. Overall PV rate was 15.6%, with 10.9% of PV in DNA repair genes. PVs were most commonly identified in BRCA2 (4.5%), CHEK2 (2.2%), ATM (1.8%), and BRCA1 (1.1%). Breast cancer family history was significantly associated with germline DNA repair PVs (OR 1.89, [95%CI 1.33, 2.68], P = 0.003). Among men with Gleason score>= 6 (n = 706), Gleason> = 8 was significantly associated with DNA repair PVs (OR 1.85 [95%CI 1.22, 2.80], P = 0.004)., Conclusions: A substantial proportion of men with PCA unselected for metastatic disease carry germline DNA repair PVs. Breast cancer family history and high Gleason score are important predictors to identify men with PCA who may carry germline DNA repair PVs. Our findings support current NCCN guidelines and have implications for genetic assessment, therapeutic management, and cascade testing for men with PCA and their families., (© 2018 Wiley Periodicals, Inc.)

Background: A point-prevalence survey that was conducted in the United States in 2011 showed that 4% of hospitalized patients had a health care-associated infection. We repeated the survey in 2015 to assess changes in the prevalence of health care-associated infections during a period of national attention to the prevention of such infections., Methods: At Emerging Infections Program sites in 10 states, we recruited up to 25 hospitals in each site area, prioritizing hospitals that had participated in the 2011 survey. Each hospital selected 1 day on which a random sample of patients was identified for assessment. Trained staff reviewed medical records using the 2011 definitions of health care-associated infections. We compared the percentages of patients with health care-associated infections and performed multivariable log-binomial regression modeling to evaluate the association of survey year with the risk of health care-associated infections., Results: In 2015, a total of 12,299 patients in 199 hospitals were surveyed, as compared with 11,282 patients in 183 hospitals in 2011. Fewer patients had health care-associated infections in 2015 (394 patients [3.2%; 95% confidence interval {CI}, 2.9 to 3.5]) than in 2011 (452 [4.0%; 95% CI, 3.7 to 4.4]) (P<0.001), largely owing to reductions in the prevalence of surgical-site and urinary tract infections. Pneumonia, gastrointestinal infections (most of which were due to Clostridium difficile [now Clostridioides difficile]), and surgical-site infections were the most common health care-associated infections. Patients' risk of having a health care-associated infection was 16% lower in 2015 than in 2011 (risk ratio, 0.84; 95% CI, 0.74 to 0.95; P=0.005), after adjustment for age, presence of devices, days from admission to survey, and status of being in a large hospital., Conclusions: The prevalence of health care-associated infections was lower in 2015 than in 2011. To continue to make progress in the prevention of such infections, prevention strategies against C. difficile infection and pneumonia should be augmented. (Funded by the Centers for Disease Control and Prevention.).

Background: An estimated 5-10% of breast and ovarian cancers are due to hereditary causes such as hereditary breast and ovarian cancer (HBOC) syndrome. Medicare, the third-party payer that covers 44 million patients in the United States, has implemented a set of clinical criteria to determine coverage for the testing of the BRCA1 and BRCA2 genes. These criteria, developed to identify carriers of BRCA1/2 variants, have not been evaluated in the panel testing era. This study investigated a series of Medicare patients undergoing genetic testing for HBOC to determine the efficacy of genetic testing criteria in identifying patients with hereditary risk., Methods: This study retrospectively examined de-identified data from a consecutive series of Medicare patients undergoing genetic testing based on personal and family history of breast and gynecologic cancer. Ordering clinicians indicated whether patients did or did not meet established criteria for BRCA1/2 genetic testing. The genetic test results were compared between the group that met the criteria and the group that did not. Patients in families with known pathogenic (P) or likely pathogenic (LP) variants were excluded from the primary analysis., Results: Among 4196 unique Medicare patients, the rate of P/LP variants for the patients who met the criteria for genetic testing was 10.5%, and for those who did not, the rate was 9% (p = 0.26)., Conclusions: The results of this study indicate that a substantial number of Medicare patients with clinically actionable genetic variants are being missed by current testing criteria and suggest the need for significant expansion and simplification of the testing criteria for HBOC.

Background: To provide a standardized, risk-adjusted method for summarizing antibiotic use (AU), enable hospitals to track their AU over time and compare their AU data to national benchmarks, the Centers for Disease Control and Prevention developed the Standardized Antimicrobial Administration Ratio (SAAR)., Methods: Hospitals reporting to the National Healthcare Safety Network (NHSN) AU Option collect and submit aggregated AU data electronically as antimicrobial days of therapy per patient days present. SAARs were developed for specific NHSN adult and pediatric patient care locations and cover five antimicrobial agent categories: (1) broad-spectrum agents predominantly used for hospital-onset/multi-drug resistant bacteria; (2) broad-spectrum agents predominantly used for community-acquired infections; (3) anti-methicillin-resistant Staphylococcus aureus agents; (4) agents predominantly used for surgical site infection prophylaxis; and (5) all antibiotic agents. The SAAR is an observed-to-predicted use ratio where predicted use is estimated from a statistical model; a SAAR of 1 indicates that observed use and predicted use are equal., Results: Most location-level SAARs were statistically significantly different than 1: adult locations up to 52% lower than 1 and up to 41% higher than 1. Median SAARs in adult and pediatric ICUs had a range of 0.667-1.119. SAAR distributions serve as an external comparison to national SAARs., Conclusions: This is the first aggregate AU metric that uses point-of-care, antimicrobial administration data electronically reported to a national surveillance system to enable risk-adjusted, AU comparisons across multiple hospitals. Endorsed by the National Quality Forum, SAARs provide AU benchmarks that stewardship programs can use to help drive improvements.

Organ fibrosis, including idiopathic pulmonary fibrosis, is associated with significant morbidity and mortality. Because currently available therapies have limited effect, there is a need to better understand the mechanisms by which organ fibrosis occurs. We have recently reported that transforming growth factor (TGF)-β, a key cytokine that promotes fibrogenesis, induces the expression of the enzymes of the de novo serine and glycine synthesis pathway in human lung fibroblasts, and that phosphoglycerate dehydrogenase (PHGDH; the first and rate-limiting enzyme of the pathway) is required to promote collagen protein synthesis downstream of TGF-β. In this study, we investigated whether inhibition of de novo serine and glycine synthesis attenuates lung fibrosis in vivo. We found that TGF-β induces mRNA and protein expression of PHGDH in murine fibroblasts. Similarly, intratracheal administration of bleomycin resulted in increased expression of PHGDH in mouse lungs, localized to fibrotic regions. Using a newly developed small molecule inhibitor of PHGDH (NCT-503), we tested whether pharmacologic inhibition of PHGDH could inhibit fibrogenesis both in vitro and in vivo. Treatment of murine and human lung fibroblasts with NCT-503 decreased TGF-β-induced collagen protein synthesis. Mice treated with the PHGDH inhibitor beginning 7 days after intratracheal instillation of bleomycin had attenuation of lung fibrosis. These results indicate that the de novo serine and glycine synthesis pathway is necessary for TGF-β-induced collagen synthesis and bleomycin-induced pulmonary fibrosis. PHGDH and other enzymes in the de novo serine and glycine synthesis pathway may be a therapeutic target for treatment of fibrotic diseases, including idiopathic pulmonary fibrosis.

Objectives: To examine access to palliative care between different disease trajectories and compare to other geographic areas., Design: A retrospective population-based decedent cohort study using linked administrative data., Setting: Ontario, Canada., Participants: Ontario decedents between 1 April 2010 and 31 December 2012. Patients were categorised into disease trajectories: terminal illness (eg, cancer), organ failure (eg, chronic heart failure), frailty (eg, dementia), sudden death or other., Interventions: Receipt of palliative care services from institutional and community settings, derived from a validated list of palliative care codes from multiple administrate databases., Outcome Measures: Receiving any palliative care services in the last year of life (yes/no), intensity (total days) and time of initiation of palliative care, in hospital and community sectors. Multivariable analysis examined the association between disease trajectory and the receipt of palliative care in the last year of life., Results: We identified 235 159 decedents in Ontario. In the last year of life, 88% of terminal illness, 44% of organ failure and 32% of frailty decedents accessed at least one palliative care service. Most care was provided during an inpatient hospitalisation. Terminal illness decedents received twice as many palliative care days (mean of 49 days) compared with organ failure and frailty decedents. Patients with terminal illness initiated palliative care median of 107 days before death compared with median of 19 days among those using the US Medicare hospice benefit., Conclusions: Terminal illness decedents are more likely to receive any palliative care, with increased intensity and earlier before death than organ failure or frailty decedents. These data serve as a useful comparison for other countries with similar and different healthcare systems and eligibility criteria., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Clinicians ordering multi-gene next-generation sequencing panels for hereditary breast cancer risk have a variety of test panel options. Many panels include lesser known breast cancer genes or genes associated with other cancers. The authors hypothesized that using broader gene panels increases the identification of clinically significant findings, some relevant and others incidental to the testing indication. They examined clinician ordering patterns and compared the yield of pathogenic or likely pathogenic (P/LP) variants in non-BRCA genes of female breast cancer patients., Methods: This study analyzed de-identified personal and family histories in 1085 breast cancer cases with P/LP multi-gene panel findings in non-BRCA cancer genes and sorted them into three groups by the panel used for testing: group A (breast cancer genes only), group B (commonly assessed cancers: breast, gynecologic, and gastrointestinal), and group C (a more expanded set of tumors). The frequency of P/LP variants in genes with established management guidelines was compared and evaluated for consistency with personal and family histories., Results: This study identified 1131 P/LP variants and compared variants in clinically actionable genes for breast and non-breast cancers. Overall, 91.5% of these variants were in genes with management guidelines. Nearly 12% were unrelated to personal or family history., Conclusion: Broader panels were used for 85.6% of our cohort (groups B and C). Although pathogenic variants in non-BRCA genes are reportedly rare, the study found that most were in clinically actionable genes. Expanded panel testing improved the identification of hereditary cancer risk. Small, breast-limited panels may miss clinically relevant findings in genes associated with other heritable cancers.

The antimicrobial use (AU) option within the National Healthcare Safety Network summarizes antimicrobial prescribing data as a standardized antimicrobial administration ratio (SAAR). A hospital's antimicrobial stewardship program found that greater involvement of an infectious disease physician in prospective audit and feedback procedures was associated with reductions in SAAR values across multiple antimicrobial categories. Infect Control Hosp Epidemiol 2017;38:721-723.

TGF-β promotes excessive collagen deposition in fibrotic diseases such as idiopathic pulmonary fibrosis (IPF). The amino acid composition of collagen is unique due to its high (33%) glycine content. Here, we report that TGF-β induces expression of glycolytic genes and increases glycolytic flux. TGF-β also induces the expression of the enzymes of the de novo serine synthesis pathway (phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH)) and de novo glycine synthesis (serine hydroxymethyltransferase 2 (SHMT2)). Studies in fibroblasts with genetic attenuation of PHGDH or SHMT2 and pharmacologic inhibition of PHGDH showed that these enzymes are required for collagen synthesis. Furthermore, metabolic labeling experiments demonstrated carbon from glucose incorporated into collagen. Lungs from humans with IPF demonstrated increased expression of PHGDH and SHMT2. These results indicate that the de novo serine synthesis pathway is necessary for TGF-β-induced collagen production and suggest that this pathway may be a therapeutic target for treatment of fibrotic diseases including IPF., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Context: Despite being commonplace in health care systems, little research has described home care nursing's effectiveness to reduce acute care use at the end of life., Objectives: To examine the temporal association between home care nursing rate on emergency department (ED) visit rate in the subsequent week during the last six months of life., Methods: We conducted a retrospective cohort study of end-of-life cancer decedents in Ontario, Canada, from 2004 to 2009 by linking administrative databases. We examined the association between home care nursing rate of one week with the ED rate in the subsequent week closer to death, controlling for covariates and repeated measures among decedents. Nursing was dichotomized into standard and end-of-life care intent., Results: Our cohort included 54,576 decedents who used home care nursing services in the last six months before death, where 85% had an ED visit and 68% received end-of-life home care nursing. Patients receiving end-of-life nursing at any week had a significantly reduced ED rate in the subsequent week of 31% (relative rate [RR] 0.69; 95% confidence interval [CI] 0.68, 0.71) compared with standard nursing. In the last month of life, receiving end-of-life nursing and standard nursing rate of more than five hours/week was associated with a decreased ED rate of 41% (RR 0.59, 95% CI 0.58, 0.61) and 32% (RR 0.68, 95% CI 0.66, 0.70), respectively, compared with standard nursing of one hour/week., Conclusion: Our study showed a temporal association between receiving end-of-life nursing in a given week during the last six months of life, and of more standard nursing in the last month of life, with a reduced ED rate in the subsequent week., (Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Uterine cancer is a major cancer of women, with outcomes potentially worsening with delayed diagnosis or hysterectomy, the main treatment. Yet cancer surgery wait times are not reported by cancer site. This study sought to examine changes in wait times for uterine cancer surgery between 2000 and 2009 and to identify predictors of longer surgery wait times., Methods: Population-based retrospective analysis of a cohort of uterine cancer patients diagnosed between April 2000 and March 2009. Using linked administrative data, all cases in which a patient had hysterectomy following diagnosis were identified. Wait time was defined as days from diagnosis of uterine cancer (day 0) to hysterectomy. Regression analysis was used to examine the relationship between covariates and wait time., Results: Wait times increased steadily between 2000 and 2006 from a median of 34 to 54 days, followed by a plateau until 2009-during which patients waited a median of between 53 and 55 days for surgery after diagnosis. Overall, 55% of patients had a wait time longer than 6 weeks after diagnosis. Predictors of a wait time greater than 6 weeks included older age, region, lower income, later year of diagnosis, surgery by a gynaecologic oncologist, non-sarcoma histology group and having surgery in a teaching hospital., Conclusion: Over half of uterine cancer patients waited longer than the recommended 6 weeks for surgery. Future reporting of cancer wait times by each disease site regularly would help to identify progress to reduce wait times and opportunities for improvement., (© 2013.)

Background: Substantial staff time and costs are incurred in the collection of data for cancer clinical trials. Anecdotal experience suggests that much of these data are never used in the analysis or reporting of a trial., Purpose: To quantify data items collected in cancer clinical trials and calculate what percentage is used in subsequent published manuscripts., Methods: Cancer clinical trials completed by the Ontario Clinical Oncology Group (OCOG) between 2003 and 2012 and the corresponding primary outcome publication were identified. The number of data items collected on each trial's case report form (CRF) was counted and sorted into 18 categories including eligibility, baseline characteristics, medical history, toxicity, and recurrence. The data items were then counted within the corresponding published manuscripts to determine percent of data used overall and within each section., Results: In all, 8 trials, with 9 corresponding publications, were evaluated. The CRF analysis revealed that the total collected items per subject ranged from 186 to 1035 per trial with a median of 599. Across all the publications, a median of 96 data items (18%) were reported in each manuscript, ranging from 11% to 27% per trial. In 8 of the 18 categories, 4% or less of collected data items were used., Limitations: The number of trials reviewed is small and were conducted from a single clinical trial coordinating centre. The main outcome of the number of data items used in the published manuscript is a surrogate for trial information considered valuable by investigators. Some data may be deemed important by investigators but not included in manuscripts., Conclusions: In this analysis of publications from 8 clinical trials, a small amount of data collected was ultimately used in peer-reviewed journal manuscripts. A large amount of data collected in cancer trials appears to go unused and could be omitted from CRFs, thus simplifying data collection and improving trial efficiency.