Implementation of an in-patient hip fracture liaison services to improve initiation of osteoporosis medication use within 1-year of hip fracture: a population-based time series analysis using the RE-AIM framework.

A hip fracture liaison service that was implemented in 2 hospitals in Alberta, Canada, co-managed by a nurse and physician, was effective for improving initiation of osteoporosis medication following hip fracture. PURPOSE: To examine implementation of an in-patient hip fracture liaison service (H-FLS) to improve osteoporosis medication use after hip fracture using the RE-AIM framework (reach, effectiveness, adoption, implementation, maintenance). METHODS: Using population-based administrative data from 7 quarters before and up to 7 quarters after H-FLS implementation, we examined new starts, continued use, and overall use (new starts + continued use) of osteoporosis medication after hip fracture. A total of 1427 patients 50 years and older that underwent hip fracture surgery at 1 of 2 tertiary hospitals in a Canadian province and survived to 12 months post-fracture were included. We also compared treatment initiation rates by sex and hospital. RESULTS: Of the 1427 patients, 1002 (70.2%) were female (mean age = 79.3 ± 11.9 years) and 425 (29.8%) were male (mean age = 73.8 ± 13.8 years). Based on pre-fracture residence within the health zone, 1101 (69%) were considered eligible (Reach). New starts of osteoporosis medication increased from 24.7% pre- to 43.9% post-implementation of the H-FLS (p < 0.001) (effectiveness). The proportion of patients prescribed osteoporosis medication prior to a hip fracture remained consistent (15.1% pre-; 14.7% post-implementation; p = 0.88) with a resultant improvement in overall medication use from 39.8% pre- to 58.6% post-implementation (p < 0.001). Both sites significantly improved medication initiation (site 1: 27.9% pre- to 40.3% post-implementation; site 2: 19.6% pre- to 50.0% post-implementation; p < 0.001 for both) (adoption). Medication initiation in females improved from 26.0% pre- to 43.4% post-implementation while initiation in males improved from 21.7% pre- to 45.1% post-implementation (p < 0.001[females]; p = 0.001[males]) (implementation). Post-implementation, elevated initiation rates were retained over the 7 quarters (p = 0.81) (maintenance). CONCLUSIONS: An H-FLS based in two tertiary hospital sites significantly improved use of osteoporosis medications after hip fracture in both males and females.

The impact of time to surgery after hip fracture on mortality at 30- and 90-days: Does a single benchmark apply to all?

INTRODUCTION: Delays to surgery after hip fracture have been associated with mortality Uncertainty remains as to what timing benchmark should be utilized as a marker of quality of care and how other patient factors might also influence the impact of time to surgery on mortality. The goal of this study was to determine how time to surgery affects 30- and 90-day mortality by age and to explore the impact of preoperative comorbid burden and sex. PARTICIPANTS: We used population-based administrative data from a Canadian province collected from 01April2008 to 31March2015. Of 12,713 Albertans 50-years and older who experienced a hip fracture and underwent surgery within 100 h of admission, 11,996 (94.8%) provided data. METHODS: Time to surgery was analyzed in hours from admission to surgery. Age and the interaction between age and time to surgery were evaluated using logistic regression. Charlson co-morbidity score and sex were also considered in the analysis. Survival was evaluated at 30-and 90-days post hip fracture using a provincial registry. RESULTS: The average age of the cohort was 79.6 ± 11.2 years and 8,412 (70.1%) were female. Overall, 586 (4.9%) patients died within 30-days and 1,023 (8.5%) died within 90-days of hip fracture. Mortality increased significantly with increasing time to surgery (30-day mortality odds ratio [OR] = 1.03; 95%CI 1.01-1.05: 90-day mortality OR = 1.03; 95% CI 1.01-1.04). Mortality also increased substantially with increasing age; those ≥85 years were 19.63 (95% CI 6.83-67.33) and 15.66 (95%CI 7.20-37.16) times the odds more likely to die relative to those between 50-64 years of age at 30-days and 90-days postoperatively respectively. Further, those who were ≥85 years were more significantly affected by increasing time to surgery than those who were 50-64 years of age at both 30-days (p = 0.04) and 90-days (p = 0.025) post-fracture. Males and those with a higher comorbid burden also had higher odds of dying after controlling for time to surgery (p < 0.001) CONCLUSION: Time to surgery following hip fracture may have a differential effect on 30- and 90-day survival dependent on age. Older patients appear to be at higher risk of dying with surgical delays than younger patients.

CpG-based immunotherapy impairs antitumor activity of BRAF inhibitors in a B-cell-dependent manner.

Combining immunotherapy with targeted therapy has increasingly become an appealing therapeutic paradigm for cancer treatment due to its great potential for generating durable and synergistic antitumor response. In this study, however, we unexpectedly found that two types of CpG-based tumor peptide vaccine treatments consistently negated the antitumor activity of a selective BRAF inhibitor in tumors with BRAF mutation rather than showing a synergistic antitumor effect. Our further studies demonstrated that CpG alone was sufficient to dampen BRAF inhibitor-induced antitumor responses, suggesting that the impaired antitumor activity of the BRAF inhibitor observed in mice receiving CpG-based peptide vaccine is mainly dependent upon the use of CpG. Mechanistically, CpG increased the number of circulating B cells, which produced elevated amounts of tumor necrosis factor-α (TNFα) that contributed to the increased tumor resistance to BRAF inhibitors. More importantly, B-cell depletion or TNFα neutralization can restore the antitumor effect of BRAF inhibition in mice receiving CpG treatment, indicating that TNFα-secreting B cells play an indispensable role in BRAF inhibitor resistance induced by CpG. Taken together, our results strongly suggest that precautions must be implemented when designing combinatorial approaches for cancer treatment, because distinct regimens, despite their respective therapeutic benefit as monotherapy, may together provide antagonistic clinical outcomes.

Malaysianol B, an oligostilbenoid derivative from Dryobalanops lanceolata.

A new oligostilbenoid tetramer, malaysianol B (1), was isolated from the acetone extract of the stem bark of Dryobalanops lanceolata along with seven oligostilbenoids tetramers; hopeaphenol (2), stenophyllol A (3), nepalensinol B (4), vaticanol B (5) and C (6), upunaphenol D (7), and flexuosol A (8). The structures of the isolated compounds were established on the basis of their spectroscopic data evidence. The antibacterial activity of the isolated compounds was evaluated using resazurin microtitre-plate assay.

Comparative effectiveness of alternative clinical pathways for primary hip and knee joint replacement patients: a pragmatic randomized, controlled trial.

OBJECTIVE: Total hip replacement (THR) and total knee replacement (TKR) (arthroplasty) surgery for end-stage osteoarthritis (OA) are ideal candidates for optimization through an algorithmic care pathway. Using a comparative effectiveness study design, we compared the effectiveness of a new clinical pathway (NCP) featuring central intake clinics, dedicated inpatient resources, care guidelines and efficiency benchmarks vs. the standard of care (SOC) for THR or TKR. METHODS: We compared patients undergoing primary THR and TKR who received surgery in NCP vs. SOC in a randomised controlled trial within the trial timeframe. 1,570 patients (1,066 SOC and 504 NCP patients) that underwent surgery within the study timeframe from urban and rural practice settings were included. The primary endpoint was improvement in Western Ontario and McMaster University osteoarthritis index (WOMAC) overall score over 12 months post-surgery. Secondary endpoints were improvements in the physical function (PF) and bodily pain (BP) domains of the Short Form 36 (SF-36). RESULTS: NCP patients had significantly greater improvements from baseline WOMAC scores compared to SOC patients after adjusting for covariates (treatment effect=2.56; 95% confidence interval (CI) [1.10-4.01]). SF-36 BP scores were significantly improved for both hip and knee patients in the NCP (treatment effect=3.01, 95% CI [0.70-5.32]), but SF-36 PF scores were not. Effects of the NCP were more pronounced in knee patients. CONCLUSION: While effect sizes were small compared with major effects of the surgery itself, an evidence-informed clinical pathway can improve health related quality of life (HRQoL) of hip and knee arthroplasty patients with degenerative joint disorder in routine clinical practice for up to 12 months post-operatively. CLINICALTRIALS.GOV IDENTIFIER: NCT00277186.

Upregulation of lactate dehydrogenase A by ErbB2 through heat shock factor 1 promotes breast cancer cell glycolysis and growth.

ErbB2 has been shown to activate signaling molecules that may regulate glucose metabolism. However, there is no evidence reported to directly link ErbB2 to glycolysis, and the mechanism underlying ErbB2-enhanced glycolysis is poorly understood. In this study, we investigated the role and mechanism of ErbB2 in regulating glycolysis. We found that ErbB2-overexpressing cells possessed a significantly higher level of glycolysis when compared to the ErbB2-low-expressing cells, and the downregulation of ErbB2 markedly decreased glycolysis. Overexpression of ErbB2 increased the expression of glycolysis-regulating molecules lactate dehydrogenase A (LDH-A) and heat shock factor 1 (HSF1). ErbB2 activated HSF1, indicated by the increased HSF1 trimer formation, and promoted HSF1 protein synthesis. HSF1 bound to LDH-A promoter and the downregulation of HSF1 reduced the expression of LDH-A and subsequently decreased cancer cell glycolysis and growth. Moreover, the glycolysis inhibitors, 2-deoxyglucose and oxamate, selectively inhibited the growth of ErbB2-overexpressing cells. Taken together, this study shows that in human breast cancer cells, ErbB2 promotes glycolysis at least partially through the HSF1-mediated upregulation of LDH-A. This pathway may have a major role in regulating glucose metabolism in breast cancer cells. These novel findings have important implications for the design of new approaches to target ErbB2-overexpressing breast cancers.

Chlorambucil-induced pulmonary disease: a case report and review of the literature.

A 77-year-old man developed pneumonitis while on chlorambucil therapy for chronic lymphocytic leukemia, with a cumulative dose of 2700 mg. The condition improved promptly with the discontinuation of the drug and initiation of steroids. A case report and review of the literature are presented in this paper.