Risk Factors for Prolonged Opioid Use Following Total Hip Arthroplasty and Total Knee Arthroplasty: A Narrative Review of Recent Literature.

OBJECTIVE: To provide pharmacists and other health care professionals with the knowledge required to minimize the risk of prolonged opioid use following total hip arthroplasty (THA) and total knee arthroplasty (TKA). DATA SOURCES: A literature search of PubMed and Embase was performed, and included the search terms: (opioid OR opiate OR opium) AND (risk factor OR predict*) AND (arthroplasty OR replacement) NOT shoulder. STUDY SELECTION AND DATA EXTRACTION: Randomized control trials, cohort studies (both prospective and retrospective), systematic reviews, and meta-analyses were included if risk ratios (RRs) or odds ratios (ORs) were reported and published within the last 5 years. DATA SYNTHESIS: ]Twenty studies met inclusion criteria, including 2 meta-analyses and 2 prospective studies. There were several risk factors that overlapped between studies and presented clinically significant risks for prolonged opioid use following THA and TKA surgery. Of these, age < 65 (RRs: 1.15-9.36), preoperative opioid use (RRs: 1.09-7.81), larger quantities of opioids prescribed at discharge (RRs: 1.26-8.81), and TKA surgery (RRs: 1.73-6.07) were the most significant. Several risk factors were recently described, including migraines (RRs: 1.14-5.11) and fibromyalgia (RRs: 1.1-2.3) that may be of interest for further research. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review presents a discussion of the factors associated with prolonged opioid use following THA and TKA surgeries, which are among the most common orthopedic surgeries. CONCLUSIONS: Prescribers should carefully consider patient-specific factors when prescribing opioids as there are several factors, including age, surgery type, and medical conditions that can predispose patients to prolonged opioid use.

Cancer and the breakdown of multicellularity: What Dictyostelium discoideum, a social amoeba, can teach us.

Ancient pathways promoting unicellularity and multicellularity are associated with cancer, the former being pro-oncogenic and the latter acting to suppress oncogenesis. However, there are only a limited number of non-vertebrate models for studying these pathways. Here, we review Dictyostelium discoideum and describe how it can be used to understand these gene networks. D. discoideum has a unicellular and multicellular life cycle, making it possible to study orthologs of cancer-associated genes in both phases. During development, differentiated amoebae form a fruiting body composed of a mass of spores that are supported atop a stalk. A portion of the cells sacrifice themselves to become non-reproductive stalk cells. Cheating disrupts the principles of multicellularity, as cheater cells alter their cell fate to preferentially become spores. Importantly, D. discoideum has gene networks and several strategies for maintaining multicellularity. Therefore, D. discoideum can help us better understand how conserved genes and pathways involved in multicellularity also influence cancer development, potentially identifying new therapeutic avenues.

Hydrogen peroxide treatment and its impacts on Lepeophtheirus salmonis originating from the Bay of Fundy, Canada.

Hydrogen peroxide (H2 O2 ) is used to treat sea lice infections of farmed salmonids in the Atlantic and Pacific Oceans and issues with resistance to this treatment, and others are a major threat to the sustainability of the industry. The objectives of this study were to determine how H2 O2 exposure affects survival and antioxidant-related gene expression in salmon lice (Lepeophtheirus salmonis) collected from the Bay of Fundy, New Brunswick. The maximum recommended dose of H2 O2 is 1,800 mg/L, while the EC50 values (with 95% CI) for the population tested were 1,486 (457, 2,515) mg/L for males and 2,126 (984, 3,268) mg/L for females. Neither temperature nor pretreatment with emamectin benzoate (EMB) impacted survival after H2 O2 exposure. RT-qPCR was performed on pre-adult sea lice exposed to H2 O2 and showed that four genes classically involved in the response to oxidative stress were unchanged between treated and control groups. Seven genes were found to be significantly upregulated in males and one in females. This is the first report on the efficacy and molecular responses of Atlantic Canada sea lice to H2 O2 treatment.

Environmental scan of current strategies to decrease sedative-hypnotic drug use and promote sleep in hospital patients.

BACKGROUND: Sedative-hypnotic drugs are often initiated in hospital to manage insomnia and anxiety. Guidelines discourage their use, particularly in older adults, due to risks of falls, fractures, and delirium. AIM: To identify publicly available resources to decrease the use of sedative-hypnotic drugs and promote sleep in hospital. METHOD: An advanced Google search with 6 search strategies was conducted. Key websites were also identified and searched. Hospital- or community-based resources using non-pharmacologic measures to reduce sedative-hypnotic drug use and/or to promote sleep were included if they were publicly available in English within the past 5 years. Full text screening and data extraction was performed independently by 2 reviewers; a third reviewer resolved disagreements by consensus. RESULTS: A total of 79 resources met inclusion criteria, with 65 (82.3%) providing education and 31 (39.2%) describing sleep hygiene strategies. Other resources included deprescribing (17, 21.5%), relaxation training (13, 16.5%), cognitive behavioural therapy for insomnia (9, 11.4%), and policies (7, 8.9%). The resources primarily targeted patients (59, 74.7%) followed by healthcare providers (9, 11.4%). There were 9 resources (11.4%) that applied to both community and hospital settings, and another 2 (2.5%) designed specifically for hospital. CONCLUSION: Many resources were available to patients and healthcare providers to reduce inappropriate or ineffective use of sedative-hypnotic drugs and promote better sleep. Specific resources for the hospital setting were infrequent and recommended that clinicians stop hospital-initiated sedatives when patients are discharged. Identified resources can be adapted by healthcare organizations to develop sedative-hypnotic prescribing programs and policies.

Opioid Prescribing Habits of Orthopedic Surgeons Following Total Hip Arthroplasty and Total Knee Arthroplasty: A Pilot Study.

Background: Adequate pain management is important in patients' recovery from total hip arthroplasty (THA) and total knee arthroplasty (TKA). Objective: To determine whether risk factors for prolonged opioid use are considered when discharge prescriptions for postoperative pain are written following THA and TKA. Methods: Opioid prescriptions written between June 14 and July 9, 2021, for patients who underwent THA or TKA were analyzed. Data were also collected on the patients' age, sex, type of surgery, type of anesthesia (regional or general), preoperative use of opioids, and preoperative use of antidepressants. Results: Among the 59 patients included in the study, the most common prescriptions were for hydromorphone 2 mg (n = 15, 25%) and hydromorphone 1 mg (n = 15, 25%). At discharge, patients received a median of 400 morphine milligram equivalents (MMEs). There was no significant difference in the quantity of opioids (MMEs) prescribed at discharge in relation to surgery type (p = 0.63), sex (p = 0.44), preoperative antidepressant use (p = 0.22), or preoperative opioid use (p = 0.97). There also appeared to be no correlation between a patient's age and MMEs at discharge (p = 0.21; r 2 = 0.028). None of these variables could be used to predict which patients would receive more than 400 MMEs. Conclusions: Patient-specific factors appeared not to be taken into consideration when opioids were prescribed for postoperative pain among patients who underwent THA or TKA.

Contexte: Une gestion adéquate de la douleur est importante pour le rétablissement des patients après une arthroplastie totale de la hanche (ATH) et une arthroplastie totale du genou (ATG). Objectif: Déterminer si les facteurs de risque relatifs à l'utilisation prolongée d'opioïdes sont pris en compte lors de la rédaction d'ordonnances de congé pour douleurs postopératoires après une ATH et une ATG. Méthodes: Les prescriptions d'opioïdes rédigées entre le 14 juin et le 9 juillet 2021 pour les patients ayant subi une ATH ou une ATG ont été analysées. Des données ont également été recueillies sur l'âge, le sexe, le type de chirurgie, le type d'anesthésie (locale ou générale), l'utilisation préopératoire d'opioïdes et l'utilisation préopératoire d'antidépresseurs. Résultats: Parmi les 59 patients compris dans l'étude, les prescriptions les plus fréquentes étaient l'hydromorphone 2 mg (n = 15; 25 %) et l'hydromorphone 1 mg (n = 15; 25 %). Les patients recevaient une médiane de 400 équivalents milligrammes de morphine (MME) au moment du congé. Aucune différence significative quant à la quantité d'opioïdes (mesurée en MME) prescrits au moment du congé en fonction du type de chirurgie (p = 0,63), du sexe (p = 0,44), de l'utilisation préopératoire d'antidépresseurs (p = 0,22) ou de l'utilisation préopératoire d'opioïdes (p = 0,97) n'a été observée. Il ne semblait pas non plus y avoir de corrélation entre l'âge d'un patient et les MME au moment du congé (p = 0,21; r 2 = 0,028). Aucune de ces variables ne pouvait être utilisée pour prédire quels patients recevraient plus de 400 MME. Conclusions: Les facteurs spécifiques au patient ne semblaient pas être pris en compte lors de la prescription d'opioïdes pour la douleur postopératoire chez les patients ayant subi une ATH ou une ATG.

LncRNA PART1 Promotes Proliferation and Migration, Is Associated with Cancer Stem Cells, and Alters the miRNA Landscape in Triple-Negative Breast Cancer.

Triple-negative breast cancers (TNBCs) are aggressive, lack targeted therapies and are enriched in cancer stem cells (CSCs). Novel therapies which target CSCs within these tumors would likely lead to improved outcomes for TNBC patients. Long non-coding RNAs (lncRNAs) are potential therapeutic targets for TNBC and CSCs. We demonstrate that lncRNA prostate androgen regulated transcript 1 (PART1) is enriched in TNBCs and in Aldefluorhigh CSCs, and is associated with worse outcomes among basal-like breast cancer patients. Although PART1 is androgen inducible in breast cancer cells, analysis of patient tumors indicates its androgen regulation has minimal clinical impact. Knockdown of PART1 in TNBC cell lines and a patient-derived xenograft decreased cell proliferation, migration, tumor growth, and mammosphere formation potential. Transcriptome analyses revealed that the lncRNA affects expression of hundreds of genes (e.g., myosin-Va, MYO5A; zinc fingers and homeoboxes protein 2, ZHX2). MiRNA 4.0 GeneChip and TaqMan assays identified multiple miRNAs that are regulated by cytoplasmic PART1, including miR-190a-3p, miR-937-5p, miR-22-5p, miR-30b-3p, and miR-6870-5p. We confirmed the novel interaction between PART1 and miR-937-5p. In general, miRNAs altered by PART1 were less abundant than PART1, potentially leading to cell line-specific effects in terms miRNA-PART1 interactions and gene regulation. Together, the altered miRNA landscape induced by PART1 explains most of the protein-coding gene regulation changes (e.g., MYO5A) induced by PART1 in TNBC.