Adverse Events and Treatment Discontinuations of Antimuscarinics for the Treatment of Overactive Bladder in Older Adults: A Systematic Review and Meta-Analysis

Introduction Antimuscarinics should be used with caution in older adults with overactive bladder (OAB) due to anticholinergic adverse events (AEs). Systematic reviews and meta-analyses (SRMAs) have analyzed safety-related outcomes but have not specified risk in the elderly, the population at highest risk for AEs. The aim of this review is to explore and evaluate AEs and treatment discontinuations in adults 65 or older taking antimuscarinics for OAB. Methods Keywords were searched in MEDLINE, EMBASE, SCOPUS, and Cochrane Central Register for Controlled Trials. Randomized controlled trials (RCTs) along with sub-analyses and pooled analyses that compared antimuscarinics to placebo or another antimuscarinic were performed in February 2015. Studies assessing AEs or treatment discontinuations in a population of adults 65 or older were included. The Jadad Criteria and McHarm Tool were used to assess the quality of the trials. Results A total of 16 studies met the inclusion criteria. Eighty AEs and 27 reasons for treatment discontinuation were described in the included studies and further explored. Anticholinergic AEs were more common in antimuscarinics compared to placebo. Incidence of dizziness, dyspepsia, and urinary retention with fesoterodine, headache with darifenacin, and urinary tract infections with solifenacin were significantly higher compared to placebo. Treatment discontinuation due to AEs and dry mouth were higher in the antimuscarinics when compared to placebo in older adults. Conclusions Treatment for overactive bladder using antimuscarinics in adults aged 65 or older resulted in significant increases in risk for several AEs compared to placebo including anticholinergic and non-anticholinergic AEs

Axl-EGFR receptor tyrosine kinase hetero-interaction provides EGFR with access to pro-invasive signalling in cancer cells

© The Author(s) 2016. Acquired resistance to conventional and targeted therapies is becoming a major hindrance in cancer management. It is increasingly clear that cancer cells are able to evolve and rewire canonical signalling pathways to their advantage, thus evading cell death and promoting cell invasion. The Axl receptor tyrosine kinase (RTK) has been shown to modulate acquired resistance to EGFR-targeted therapies in both breast and lung cancers. Glioblastoma multiforme (GBM) is a highly infiltrative and invasive form of brain tumour with little response to therapy. Both Axl and EGFR have been identified as major players in gliomagenesis and invasiveness. However, the mechanisms underlying a potential signalling crosstalk between EGFR and Axl RTKs are unknown. The purpose of this study was to investigate this novel and unconventional interaction among RTKs of different families in human GBM cells. With the use of western blotting, in vitro kinase activity, co-immunoprecipitation and bimolecular fluorescence complementation assays, we show that EGF stimulates activation of Axl kinase and that there is a hetero-interaction between the two RTKs. Through small interfering RNA knockdown and quantitative PCR screening, we identified distinct gene expression patterns in GBM cells that were specifically regulated by signalling from EGFR-EGFR, Axl-Axl and EGFR-Axl RTK parings. These included genes that promote invasion, which were activated only via the EGFR-Axl axis (MMP9), while EGFR-EGFR distinctly regulated the cell cycle and Axl-Axl regulated invasion. Our findings provide critical insights into the role of EGFR-Axl hetero-dimerisation in cancer cells and reveal regulation of cell invasion via Axl as a novel function of EGFR signalling

Changes in Opioid Use After Florida's Restriction Law for Acute Pain Prescriptions

Several US states have enacted laws to limit either opioid prescription days’ supply or morphine milligram equivalents for the treatment of acute pain. On July 1, 2018, Florida implemented House Bill 21 (HB21), which limits the days’ supply of Schedule II opioids to 3 days for acute pain prescriptions. Prescribers can extend to a 7-day supply if they document an exception. This quality improvement study aims to assess the outcomes associated with Florida’s restriction law on opioid prescribing by evaluating the number of new opioid users and the number of units dispensed per prescription before and after the policy change

Trends in Use of Prescription Nonsteroidal Anti-inflammatory Medications before vs after Implementation of a Florida Law Restricting Opioid Prescribing for Acute Pain

Importance: Previous research has shown an immediate reduction in new opioid users and use after implementation of the opioid supply restriction laws. Assessment of the association between opioid restrictions and alternative treatment options, such as nonsteroidal anti-inflammatory drugs (NSAIDs), is needed to evaluate potential unintended consequences for patients requiring analgesia. Objective: To evaluate the association between an opioid restriction law in Florida and use of prescription NSAIDs. Design, Setting, and Participants: This quality improvement study used interrupted time series analyses accounting for autocorrelation to estimate immediate and trend changes in the prescribing and use of prescription NSAIDs in Florida before and after implementation of a state law limiting opioid prescriptions to a 3-day supply. Participants were enrollees in a single private health plan of a large university and health system employer in Florida from January 2015 to June 2019. Exposures: Prescriptions for NSAIDs, ascertained from pharmacy claims data. Main Outcomes and Measures: The following outcomes were calculated monthly per 1000 plan enrollees: (1) number of NSAID users; (2) mean days' supply of NSAIDs per prescription; and (3) mean number of NSAID prescriptions. Individuals were classified as NSAID users if they had at least 1 NSAID prescription in a given month. Analysis was stratified by route of NSAID administration (oral or nonoral). Results: Among 46783 NSAID users with 79089 NSAID prescriptions during the study period, the median age was 47 years (interquartile range, 35-57 years). After implementation of the opioid restriction law, the number of NSAID users immediately increased, but the difference was not significant (change, 0.82 per 1000 patients; 95% CI, -0.67 to 2.30 per 1000 patients). No significant change in the days' supply of oral NSAID users occurred (change, 0.21 days per prescription; 95% CI, -1.66 to 2.08 days per prescription). Before implementation of the law, there was a nonsignificant decreasing trend in NSAID prescriptions (rate of change, -0.03 per month per 1000 enrollees; 95% CI, -0.13 to 0.07 per month per 1000 enrollees; after implementation, there was a nonsignificant increase in the number of oral and nonoral NSAID prescriptions (change, 1.49 per 1000 enrollees; 95% CI, -3.38 to 6.37 per 1000 enrollees). Conclusions and Relevance: In this quality improvement study, prescribing and use of prescription NSAIDs did not increase after implementation of a law restricting opioid analgesic prescriptions in Florida. These findings suggest possible greater use of over-the-counter NSAIDs after implementation of the law, but further research is needed to evaluate changes in the use of nonopioid analgesics and alternative pain therapies

Changes in Prescribing by Provider Type Following a State Prescription Opioid Restriction Law

Background: Many states have implemented opioid days’ supply restriction policies, leading to reductions in opioid prescribing. Although research within certain provider types exist, no study has evaluated a restriction policy by various provider types. Objective: To evaluate changes in opioid utilization following a days’ supply restriction policy stratified by provider type: surgery, emergency medicine, primary care, specialty care, and dentistry. Design: Interrupted time series (ITS) Participants: Opioid prescription claims of patients in a private health plan serving a large Florida employer from 1/1/2015 to 3/31/2019. Provider types were determined using the Healthcare Provider Taxonomy Code associated with the national provider identifier (NPI). Interventions: Florida’s opioid restriction policy implemented on July 1, 2018. Main Measures: Changes in mean morphine milligram equivalent (MMEs), mean days’ supply, and mean number of units dispensed per opioid prescription before and after policy implementation. Key Results: There were 10,583 opioid initial prescriptions dispensed. Treating providers were classified as surgery (16.4%; n = 1732), emergency care (14.3%; n = 1516), primary care (21.2%; n = 2241), specialty care (11.4%; n = 1207), and dentistry providers (23.7%; n = 2511). Significant reductions in mean days’ supply were observed across most provider types ranging from 14% reduction for dentistry providers to 41% reduction for specialty care providers. Significant changes were observed for emergency care and specialty care providers with a 30% (p = 0.001)and 29% (p < 0.001) reduction in mean MME, respectively, and a 27% (p = 0.040) reduction in mean number of units dispensed in emergency care providers, after implementation. Pre-implementation trends in opioid prescribing varied by provider type impacting the effects of the opioid days’ supply restriction policy. Conclusions: Pre-policy opioid prescribing varied by provider type with a differential impact on mean MMEs, mean days’ supply, and mean number of units dispensed per prescription following implementation

Impact of co-investigators on pharmacy resident research publication

Objective: To explore influences of co-investigators on the successful publication of a pharmacy residency project.Methods: We analyzed published and non-published research presented at a regional pharmacy conference. Abstracts were matched 1:1 based on state and abstract year. We assessed university affiliation, number, degree, and H-Index of co-investigators on the abstract. Descriptive and inferential analyses were used to identify variables associated with resident publication.Results: University-affiliated programs (p=0.015), highest H-Index of a non-physician co-investigator (p=0.002), and positive H-Index (≥1) of a non-physician co-investigator (p=0.017) were significant predictors of resident publication on univariate analyses. There were no differences in the number of co-investigators (p=0.051), projects with physician co-investigators (p=1.000), or projects with Doctor of Philosophy (PhD) or Master of Science (MS) co-investigators (p=0.536) between published and non-published projects. Multivariate analysis found that the highest H-index of non-physician co-investigator remained significant as a predictor to resident publication (odds ratio (OR) 1.09, 95% Confidence Interval (CI) 1.01-1.17).Conclusions: The quality of co-investigators, as measured by an increasing H-Index, is associated with the successful publication of residency projects. More emphasis may need to be placed on resident research co-investigator selection and training to prepare pharmacy residents for research and scholarly activity