Changing from mandatory to optional genotyping results in higher acceptance of pharmacist-guided warfarin dosing

Aim: We evaluated the clinical acceptance and feasibility of a pharmacist-guided personalized consult service following its transition from a mandatory (mPGx) to optional (oPGx) CYP2C9/ VKORC1/ CYP4F2 genotyping for warfarin. Methods: A total of 1105 patients were included. Clinical acceptance and feasibility outcomes were analyzed using bivariate and multivariable analyses. Results: After transitioning to optional genotyping, genotype testing was still ordered in a large segment of the eligible population (52.1%). Physician acceptance of pharmacist-recommended doses improved from 83.9% (mPGx) to 86.6% (oPGx; OR: 1.3; 95% CI: 1.1–1.5; p = 0.01) with a shorter median genotype result turnaround time (oPGX: 23.6 hr vs mPGX: 25.1 hr ; p < 0.01). Conclusion: Ordering of genotype testing and provider acceptance of dosing recommendations remained high after transitioning to optional genotyping.

The Heart and Cannabis (THC) Cohort: Differences in Baseline Health and Behaviors by Cannabis Use

Background Evidence on the cardiovascular health effects of cannabis use is limited. We designed a prospective cohort study of older Veterans (66 to 68 years) with coronary artery disease (CAD) to understand the cardiovascular consequences of cannabis use. We describe the cohort construction, baseline characteristics, and health behaviors that were associated with smoking cannabis. Objective To understand the cardiovascular consequences of cannabis use. Design We designed a prospective cohort study of older Veterans (66 to 68 years) with CAD. Participants A total of 1,015 current cannabis smokers and 3,270 non-cannabis smokers with CAD. Main Measures Using logistic regression, we examined the association of baseline variables with smoking cannabis in the past 30 days. Results The current cannabis smokers and non-current smokers were predominantly male (97.2% vs 97.1%, p=0.96). Characteristics associated with recent cannabis use in multivariable analyses included lack of a high school education (odds ratio [OR] 2.15, 95% confidence interval [CI]: 1.10 to 4.19), financial difficulty (OR 1.47, 95% CI: 1.02 to 2.11), tobacco use (OR 3.02, 95% CI: 1.66 to 5.48), current drug use (OR 2.82, 95% CI: 1.06 to 7.46), and prior drug use (OR 2.84, 95% CI: 2.11 to 3.82). In contrast, compared to individuals with 0 to 1 comorbid conditions, those with 5 chronic conditions or more (OR 0.43, 95% CI: 0.27 to 0.70) were less likely to smoke cannabis. Conclusions In this older high-risk cohort, smoking cannabis was associated with higher social and behavioral risk, but with fewer chronic health conditions.

Sugar-sweetened beverage consumption and breast composition in a longitudinal study of Chilean girls

Background Frequent sugar-sweetened beverage (SSB) intake has been associated with indirect markers of breast cancer risk, such as weight gain in adolescents and early menarche. How SSB intake relates to breast composition in adolescent girls has not been explored. Methods We evaluated the association between prospective intake of SSB and breast density in a cohort of 374 adolescent girls participating in the Growth and Obesity Cohort Study in Santiago, Chile. Multivariable linear regression models were used to analyze the association between average daily SSB intake quartiles and breast composition (absolute fibroglandular volume [aFGV], percent fibroglandular volume [%FGV], total breast volume [tBV]). Models were adjusted for potential confounding by BMI Z-score, age, daily energy intake (g/day), maternal education, hours of daily television watching after school, dairy intake (g/day), meat intake (g/day), waist circumference, and menarche. To examine the sensitivity of the association to the number of dietary recalls for each girl, analyses were further stratified by girls with one dietary recall and girls with > one dietary recall. Results A total of 881 dietary recalls were available for 374 girls prior to the breast density assessment. More than 60% of the cohort had > one dietary recall available. In multivariable analyses, we found no association between SSB intake quartile and aFGV (Q2 vs Q1 β: − 5.4, 95% CI − 15.1, 4.4; Q3 vs Q1 β: 1.3, 95% CI − 8.6, 11.3; Q4 vs Q1 β: 3.0, 95% CI − 7.1, 13). No associations were noted for %FGV and tBV. Among girls with at least one dietary recall, we found no significant associations between SSB intake quartiles and %FGV, aFGV, or tBV. Conclusion Overall, we observed no evidence that SSB intake was associated with breast density in adolescent Chilean girls.

Prognostic value of hepatocyte growth factor for muscle-invasive bladder cancer

Purpose The HGF/MET pathway is involved in cell motility, angiogenesis, proliferation, and cancer invasion. We assessed the clinical utility of plasma HGF level as a prognostic biomarker in patients with MIBC. Methods We retrospectively analyzed 565 patients with MIBC who underwent radical cystectomy. Logistic regression and Cox regression models were used, and predictive accuracies were estimated using the area under the curve and concordance index. To estimate the clinical utility of HGF, DCA and MCID were applied. Results Plasma HGF level was significantly higher in patients with advanced pathologic stage and LN metastasis (p = 0.01 and p < 0.001, respectively). Higher HGF levels were associated with an increased risk of harboring LN metastasis and non-organ-confined disease (OR1.21, 95%CI 1.12–1.32, p < 0.001, and OR1.35, 95%CI 1.23–1.48, p < 0.001, respectively) on multivariable analyses; the addition of HGF improved the predictive accuracies of a standard preoperative model (+ 7%, p < 0.001 and + 8%, p < 0.001, respectively). According to the DCA and MCID, half of the patients had a net benefit by including HGF, but the absolute magnitude remained limited. In pre- and postoperative predictive models, a higher HGF level was significant prognosticator of worse RFS, OS, and CSS; in the preoperative model, the addition of HGF improved accuracies by 6% and 5% for RFS and CSS, respectively. Conclusion Preoperative HGF identified MIBC patients who harbored features of clinically and biologically aggressive disease. Plasma HGF could serve, as part of a panel, as a biomarker to aid in preoperative treatment planning regarding intensity of treatment in patients with clinical MIBC.

Outcome of ERCP related to case-volume

Background and aims In some studies, high endoscopic retrograde cholangiopancreatography (ERCP) case-volume has been shown to correlate to high success rate in terms of successful cannulation and fewer adverse events. The aim of this study was to analyze the association between ERCP success and complications, and endoscopist and centre case-volumes. Methods Data were obtained from the Swedish National Register for Gallstone Surgery and ERCP (GallRiks) on all ERCPs performed for Common Bile Duct Stone (CBDS) (n = 17,873) and suspected or confirmed malignancy (n = 6152) between 2009 and 2018. Successful cannulation rate, procedure time, intra- and postoperative complication rates and post-ERCP pancreatitis (PEP) rate, were compared with endoscopist and centre ERCP case-volumes during the year preceding the procedure as predictor. Results In multivariable analyses of the CBDS group adjusting for age, gender and year, a high endoscopist case-volume was associated with higher successful cannulation rate, lower complication and PEP rates, and shorter procedure time (p < 0.05). Centres with a high annual case-volume were associated with high successful cannulation rate and shorter procedure time (p < 0.05), but not lower complication and PEP rates. When indication for ERCP was malignancy, a high endoscopist case-volume was associated with high successful cannulation rate and low PEP rates (p < 0.05), but not shorter procedure time or low complication rate. Centres with high case-volume were associated with high successful cannulation rate and low complication and PEP rates (p < 0.05), but not shorter procedure time. Conclusions The results suggest that higher endoscopist and centre case-volumes are associated with safer ERCP and successful outcome.

Complications, prognostic factors, and long-term outcomes for dogs with brachycephalic obstructive airway syndrome that underwent H-pharyngoplasty and ala-vestibuloplasty: 423 cases (2011–2017)

OBJECTIVE To describe the H-pharyngoplasty procedure, report the outcomes of dogs with brachycephalic obstructive airway syndrome (BOAS) treated with ala-vestibuloplasty and H-pharyngoplasty with a CO2 laser, and identify prognostic factors. ANIMALS 423 dogs. PROCEDURES Medical records of dogs admitted for BOAS from 2011 to 2017 were reviewed. Dogs were included if they were treated with ala-vestibuloplasty and H-pharyngoplasty with a CO2 laser. Signalment, physical examination findings, grades at admission of clinical signs associated with respiratory and digestive systems, diagnostic test results, postoperative treatments, and short-term follow-up results were extracted from medical records. Long-term follow-up of > 12 months was evaluated via questionnaire. Generalized ordered logistic regression was used for bivariable and multivariable analyses. RESULTS Overall mortality rate was 2.6%. Median duration of follow-up was 36 months (12 to 91 months), and 341 (80.6%) dog owners completed the questionnaire. Major complications included respiratory distress (2.1%), heatstroke (0.5%), and bronchopneumonia (0.5%). No dogs required revision surgery. Improvement in signs associated with the respiratory and digestive systems was reported in 72% and 34% of the dogs, respectively, and owners’ satisfaction was high (97.1%). Risk of death increased by 29.8% (95% CI, 11.8% to 50.7%) for every 1-year increase in age. CONCLUSION AND CLINICAL RELEVANCE H-pharyngoplasty was possible in all dogs with BOAS, including those previously treated with conventional surgery and was associated with low morbidity and improved respiratory and digestive signs. H-pharyngoplasty combined with ala-vestibuloplasty may be an alternative treatment for even the most severely affected dogs.

Radiologic response as a prognostic factor in advanced hepatocellular carcinoma with macroscopic vascular invasion after transarterial chemoembolization and radiotherapy

Introduction: We evaluated the radiologic response rate of combined transarterial chemoembolization (TACE) plus radiotherapy (RT) in treatment-naïve patients with liver-confined hepatocellular carcinoma (HCC) with macroscopic vascular invasion (MVI) and analyzed its clinical importance in overall survival (OS) outcomes. Methods: Patients who were treated with TACE plus RT as a first-line treatment for HCC with MVI between January 2010 and December 2015 were retrospectively reviewed. Radiologic response was assessed according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) at 2- and 4-months after completion of RT. Landmark analysis at 2- and 4-months and time-dependent Cox regression analysis using response as a time-dependent covariate were performed for univariable and multivariable analyses. Results: The 2-month landmark analysis included 427 patients, and the 4-month landmark analysis included 355 patients after excluding patients without imaging studies for response evaluation at 4 months. Radiologic responses were observed in 210 (49.2%) patients at 2 months and 181 (51.8%) at 4 months. In multivariable analyses, radiologic response was identified as an independent prognosticator for OS at 2 months (median OS: responders, 23.1 months vs. non-responders, 8.0 months; hazard ratio [HR], 3.194; P < 0.001) and 4 months (median OS: responders, 26.5 months vs. non-responders, 9.3 months; HR, 4.534; P < 0.001). Conclusion: Radiologic response assessed by mRECIST was a significant prognostic factor for OS in patients with advanced-stage HCC showing MVI treated with combined TACE plus RT.

Clinical Features and Risk Factors for Gastrointestinal Complications in Dogs Treated Surgically for Thoracolumbar Intervertebral Disc Extrusion

Gastrointestinal (GI) complications and their clinical implications are poorly characterized in dogs treated surgically for acute thoracolumbar intervertebral disc extrusion (TL-IVDE). The objective of this retrospective study was to characterize GI signs (including vomiting, diarrhea, melena, and hematochezia) in dogs undergoing hemilaminectomy for acute TL-IVDE. One-hundred and sixteen dogs were included. Frequency, type and severity of GI signs during hospitalization, duration of hospitalization and outcome were obtained from the medical record. Potential risk factors for the development of GI signs were explored using univariable and multivariable analyses. Gastrointestinal signs occurred in 55/116 dogs (47%); 22/55 dogs (40%) had one episode and 21/55 (38%) had ≥5 episodes. Diarrhea was the most common (40/55, 73%) while melena was rare (1/55, 2%). GI signs developed in 8/11 dogs (73%) treated perioperatively with both non-steroidal anti-inflammatories and corticosteroids with or without a washout period and in 25/52 dogs (48%) treated prophylactically with proton pump inhibitors. Median hospitalization was 7 days (4–15 days) vs. 5 days (4–11 days) in dogs with or without GI signs, respectively. Duration of hospitalization was associated with development of any GI signs, diarrhea and more severe GI signs (p = 0.001, 0.005, 0.021, respectively). Pre-operative paraplegia with absent pain perception was identified on univariable analysis (p = 0.005) and longer anesthetic duration on multivariable analysis to be associated with development of more severe GI signs (p = 0.047). In dogs undergoing surgery for acute TL-IVDE, GI signs were common and associated with duration of hospitalization and anesthesia. The influence of specific medications and neurologic severity on development of GI signs requires further investigation.

Rheumatoid Arthritis is a Risk Factor for Refracture in Patients with Fragility Fractures

Objectives To determine whether patients with rheumatoid arthritis (RA) who have had fragility fractures are at an increased risk of refractures. Methods Patients with fragility fractures who were treated surgically at ten hospitals from 2008 to 2017 and who underwent follow-up for more than 24 months were either categorized into a group comprising patients with RA or a group comprising patients without RA (controls). The groups were matched 1:1 by propensity score matching. Accordingly, 240 matched participants were included in this study. The primary outcome was the refracture rate in patients with RA as compared to in the controls. Multivariable analyses were also conducted on patients with RA to evaluate the odds ratios (ORs) for the refracture rates. Results Patients with RA were significantly associated with increased rates of refractures during the first 24 months (OR: 2.714, 95% confidence interval [95% CI]: 1.015–7.255; P = 0.040). Multivariable analyses revealed a significant association between increased refracture rates and long-term RA (OR: 6.308, 95% CI: 1.195–33.292; P=0.030). Conclusions Patients with RA who have experienced fragility fractures are at an increased risk of refractures. Long-term RA is a substantial risk factor for refractures.

Outcomes Based on Plasma Biomarkers for the Phase 3 CELESTIAL Trial of Cabozantinib versus Placebo in Advanced Hepatocellular Carcinoma

<b><i>Introduction:</i></b> Cabozantinib, an inhibitor of MET, AXL, and VEGF receptors, significantly improved overall survival (OS) and progression-free survival (PFS) versus placebo in patients with previously treated advanced hepatocellular carcinoma (HCC). In this exploratory analysis, outcomes were evaluated according to plasma biomarker levels. <b><i>Methods:</i></b> Baseline plasma levels were evaluated for MET, AXL, VEGFR2, HGF, GAS6, VEGF-A, PlGF, IL-8, EPO, ANG2, IGF-1, VEGF-C, and c-KIT for 674/707 randomized patients; and Week 4 levels were evaluated for MET, AXL, VEGFR2, HGF, GAS6, VEGF-A, PlGF, IL-8, and EPO for 614 patients. OS and PFS were analyzed by baseline levels as dichotomized or continuous variables and by on-treatment changes at Week 4 as continuous variables; biomarkers were considered potentially prognostic if <i>p</i> &#x3c; 0.05 and predictive if <i>p</i> &#x3c; 0.05 for the interaction between treatment and the biomarker. Multivariable analyses adjusting for clinical covariates were also performed. <b><i>Results:</i></b> In the placebo group, high levels of MET, HGF, GAS6, IL-8, and ANG2 and low levels of IGF-1 were associated with shorter OS in univariate and multivariable analyses; these associations were also observed for MET, IL-8, and ANG2 in the cabozantinib group. Hazard ratios for OS and PFS favored cabozantinib over the placebo at low and high baseline levels for all biomarkers. No baseline biomarkers were predictive of a treatment benefit. Cabozantinib promoted pharmacodynamic changes in several biomarkers, including increases in VEGF-A, PlGF, AXL, and GAS6 levels and decreases in VEGFR2 and HGF levels; these changes were not associated with OS or PFS. <b><i>Conclusion:</i></b> Cabozantinib improved OS and PFS versus placebo at high and low baseline concentrations for all biomarkers analyzed. Low baseline levels of MET, HGF, GAS6, IL-8, and ANG2 and high levels of IGF-1 were identified as potential favorable prognostic biomarkers for survival in previously treated advanced HCC. Although cabozantinib promoted pharmacodynamic changes in several biomarkers, these changes were not associated with survival.