Inshore and offshore marine migration pathways of Atlantic salmon post-smolts from multiple rivers in Scotland, England, Northern Ireland, and Ireland.

The migratory behavior of Atlantic salmon (Salmo salar) post-smolts in coastal waters is poorly understood. In this collaborative study, 1914 smolts, from 25 rivers, in four countries were tagged with acoustic transmitters during a single seasonal migration. In total, 1105 post-smolts entered the marine study areas and 438 (39.6%) were detected on a network of 414 marine acoustic receivers and an autonomous underwater vehicle. Migration pathways (defined as the shortest distance between two detections) of up to 575 km and over 100 days at sea were described for all 25 populations. Post-smolts from different rivers, as well as individuals from the same river, used different pathways in coastal waters. Although difficult to generalize to all rivers, at least during the year of this study, no tagged post-smolts from rivers draining into the Irish Sea were detected entering the areas of sea between the Hebrides and mainland Scotland, which is associated with a high density of finfish aquaculture. An important outcome of this study is that a high proportion of post-smolts crossed through multiple legislative jurisdictions and boundaries during their migration. This study provides the basis for spatially explicit assessment of the impact risk of coastal pressures on salmon during their first migration to sea.

Co-designing an online treatment decision aid for men with low-risk prostate cancer: Navigate.

Objectives: To develop an online treatment decision aid (OTDA) to assist patients with low-risk prostate cancer (LRPC) and their partners in making treatment decisions. Patients and methods: Navigate, an OTDA for LRPC, was rigorously co-designed by patients with a confirmed diagnosis or at risk of LRPC and their partners, clinicians, researchers and website designers/developers. A theoretical model guided the development process. A mixed methods approach was used incorporating (1) evidence for essential design elements for OTDAs; (2) evidence for treatment options for LRPC; (3) an iterative co-design process involving stakeholder workshops and prototype review; and (4) expert rating using the International Patient Decision Aid Standards (IPDAS). Three co-design workshops with potential users (n = 12) and research and web-design team members (n = 10) were conducted. Results from each workshop informed OTDA modifications to the OTDA for testing in the subsequent workshop. Clinician (n = 6) and consumer (n = 9) feedback on usability and content on the penultimate version was collected. Results: The initial workshops identified key content and design features that were incorporated into the draft OTDA, re-workshopped and incorporated into the penultimate OTDA. Expert feedback on usability and content was also incorporated into the final OTDA. The final OTDA was deemed comprehensive, clear and appropriate and met all IPDAS criteria. Conclusion: Navigate is an interactive and acceptable OTDA for Australian men with LRPC designed by men for men using a co-design methodology. The effectiveness of Navigate in assisting patient decision-making is currently being assessed in a randomised controlled trial with patients with LRPC and their partners.

Prescription opioid utilization patterns, and associated outcomes, among privately insured patients prescribed opioids to manage pain associated with osteoarthritis.

OBJECTIVE: To describe utilization patterns, negative clinical outcomes and economic burden of patients diagnosed with osteoarthritis (OA) of the hip and/or knee who received a prescription for tramadol or non-tramadol opioids vs. non-opioid drugs. METHODS: Optum Healthcare Solutions, Inc. commercial claims data were used (1/2012--3/2017). Adults with ≥2 diagnoses of OA of the hip and/or knee, and ≥30 days supply of pain medications were identified during the three-year period from the date of first prescription (index date) after the first OA diagnosis. Drug utilization statistics in the follow-up period were summarized by initial treatment (i.e. tramadol, non-tramadol opioids, non-opioid drugs). Opioid initiators were matched to those initiated on non-opioid treatments using a propensity score model accounting for baseline characteristics. Matched pairs analysis compared outcomes for these cohorts. RESULTS: Of 62,715 total patients, 15,270 (24.3%) initiated treatment with opioids, including 3,513 (5.6%) on tramadol and 11,757 (18.7%) on non-tramadol opioids. Opioid initiators had more comorbidities, higher baseline healthcare costs, and were more likely to have OA of the hip. Among non-opioid initiators, 27.5% switched to tramadol and 63% switched to non-tramadol opioids. Among tramadol initiators, 71% switched to non-tramadol opioids. Patients initiated on opioids had 20.4% (p < .01) higher all-cause healthcare costs and higher percentages experiencing multiple negative clinical outcomes (all p < .01) compared to matched controls. CONCLUSIONS: Most patients with OA of the hip and/or knee either initiate on or switch to opioids for long-term management of OA-related pain despite known risks. This highlights the need for new treatments that delay or prevent use of opioids.

Hamamelis virginiana L. Leaf Extracts Inhibit the Growth of Antibiotic-Resistant Gram-Positive and Gram-Negative Bacteria.

Virginian witch hazel (WH; Hamamelis virginiana L.; family: Hamamelidaceae) is a North American plant that is used traditionally to treat a variety of ailments, including bacterial infections. Solvents of varying polarity (water, methanol, ethyl acetate, hexane and chloroform) were used to prepare extracts from this plant. Resuspensions of each extract in an aqueous solution were tested for growth-inhibitory activity against a panel of bacteria (including three antibiotic-resistant strains) using agar disc diffusion and broth microdilution assays. The ethyl acetate, hexane and chloroform extracts were completely ineffective. However, the water and methanolic extracts were good inhibitors of E. coli, ESBL E. coli, S. aureus, MRSA, K. pneumoniae and ESBL K. pneumoniae growth, with the methanolic extract generally displaying substantially greater potency than the other extracts. Combining the active extracts with selected conventional antibiotics potentiated the bacterial growth inhibition of some combinations, whilst other combinations remained non-interactive. No synergistic or antagonistic interactions were observed for any WH extracts/antibiotic combinations. Gas chromatography-mass spectrometry analysis of the extracts identified three molecules of interest that may contribute to the activities observed, including phthalane and two 1,3-dioxolane compounds. Putative modes of action of the active WH extracts and these molecules of interest are discussed herein.

Material extrusion of thermoplastic acrylic for intraoral devices: Technical feasibility and evaluation.

With global demand for 3D printed medical devices on the rise, the search for safer, inexpensive, and sustainable methods is timely. Herein, we assessed the practicality of the material extrusion process for acrylic denture bases of which successful outcomes can be extended to implant surgical guides, orthodontic splints, impression trays, record bases and obturators for cleft palates or other maxillary defects. Representative materials comprising denture prototypes and test samples were designed and built with in-house polymethylmethacrylate filaments using varying print directions (PDs), layer heights (LHs) and reinforcements (RFs) with short glass fiber. The study undertook a comprehensive evaluation of the materials to determine their flexural, fracture, and thermal properties. Additional analyses for tensile and compressive properties, chemical composition, residual monomer, and surface roughness (Ra) were completed for parts with optimum parameters. Micrographic analysis of the acrylic composites revealed adequate fiber-matrix compatibility and predictably, their mechanical properties improved simultaneously with RFs and decreased LHs. Fiber reinforcement also improved the overall thermal conductivity of the materials. Ra, on the other hand, improved visibly with decreased RFs and LHs and the prototypes were effortlessly polished and characterized with veneering composites to mimic gingival tissues. In terms of chemical stability, the residual methyl methacrylate monomer contents are well below standards threshold for biological reactions. Notably, 5 vol% acrylic composites built with 0.05 mm LH in 0° on z-axis produced optimum properties that are superior to those of conventional acrylic, milled acrylic and 3D printed photopolymers. Finite element modeling successfully replicated the tensile properties of the prototypes. It may well be argued that the material extrusion process is cost-effective; however, the speed of manufacturing could be longer than that of established methods. Although the mean Ra is within an acceptable range, mandatory manual finishing and aesthetic pigmentation are required for long-term intraoral use. At a proof-of-concept level, it is evident that the material extrusion process can be applied to build inexpensive, safe, and robust thermoplastic acrylic devices. The broad outcomes of this novel study are equally worthy of academic reflection, and further translation to the clinic.

Evaluation of the validity and screening performance of a revised single-item fear of cancer recurrence screening measure (FCR-1r).

OBJECTIVE: Fear of cancer recurrence (FCR) is highly prevalent among cancer survivors, but irregularly identified in practice. Single-item FCR measures suitable for integration into broader psychosocial screening are needed. This study evaluated the validity of a revised version of the original FCR-1 (FCR-1r) and screening performance alongside the Edmonton Symptom Assessment System - Revised (ESAS-r) anxiety item. METHODS: The FCR-1r was adapted from the FCR-1 and modelled on the ESAS-r. Associations between FCR-1r and FCR Inventory-Short Form (FCRI-SF) scores determined concurrent validity. Relationships of FCR-1r scores with variables related (e.g., anxiety, intrusive thoughts) and unrelated (e.g., employment/marital status) to FCR determined convergent and divergent validity respectively. A Receiver-Operating Characteristic analysis examined screening performance and cut-offs for the FCR-1r and ESAS-r anxiety item. RESULTS: 107 participants were recruited in two studies (Study 1, July-October 2021, n = 54; Study 2: November 2021-May 2022, n = 53). The FCR-1r demonstrated concurrent validity against the FCRI-SF (r = 0.83, p < 0.0001) and convergent validity versus the Generalised Anxiety Disorder-7 (r = 0.63, p < 0.0001) and Impact of Event Scale-Revised Intrusion subscale (r = 0.55, p < 0.0001). It did not correlate with unrelated variables (e.g., employment/marital status), indicating divergent validity. An FCR-1r cut-off ≥5/10 had 95% sensitivity and 77% specificity for detecting clinical FCR (area under the curve (AUC) = 0.91, 95% CI 0.85-0.97, p < 0.0001); ESAS-r anxiety cut-off ≥4 had 91% sensitivity and 82% specificity (AUC = 0.87, 95% CI 0.77-0.98, p < 0.0001). CONCLUSIONS: The FCR-1r is a valid and accurate tool for FCR screening. Further evaluation of the screening performance of the FCR-1r versus the ESAS-r anxiety item in routine care is needed.

Don't bring COVID home for Christmas - analysing emerging themes during COVID-19 through lenses of care homes and universities in Finland, Northern Ireland, Scotland and Sweden.

BACKGROUND: In autumn of 2020, the UK Secretary of State for Health and Social Care pleaded with young people to 'not kill your gran' when returning home, after he confirmed the surge in coronavirus cases at that time was associated with students away from home for the first time. Meanwhile residents continued to die in care homes across the NPA Region. AIMS: To examine the impact of COVID-19 on communities through the twin lenses of University Campuses and Care Homes from November 2020 to March 2021.To generalise findings to society as a whole through the NPA Covid-19 themes of clinical aspects, health and wellbeing, technology solutions, citizen engagement/community response and economic impacts. METHODS: Surveys and 1:1 interviews via zoom or telephone gathered data. Informed consent was obtained from all participants including students, care home residents, the families of care home residents and care home workers. They were recruited via flyers and completing a Survey Monkey questionnaire. RESULTS: Mistakes made at Government level is also a common feature. In Scotland and Northern Ireland this was centred around the movement of people from hospital into the care home sector without sufficient testing, preparedness (PPE/isolation) or resources, whilst in Sweden and Finland it focused more on a reliance on soft law. The project was selected to be presented virtually at the European Regions week as well as at the the Arctic Circle Assembly in Iceland in October 2021. DISCUSSION: Among students, there was little awareness that they might be asymptomatic and could infect vulnerable contacts by bringing COVID home for Christmas In care homes, residents continued to die, and experiments took place using digital interventions to monitor social distancing and afford more access for family members.

Evaluation of the diffusion of triamcinolone and demeclocycline through the dentinal tubules and apical foramen: A mass spectrometry study.

Aim: The aim of this study was to investigate the diffusion of triamcinolone and demeclocycline from an endodontic paste when used unmodified, versus when combined in equal parts with a calcium hydroxide paste, in terms of diffusion through the dentinal tubules versus through the apical foramen. Methodology: Medicaments were placed in endodontically prepared roots that were kept in vials of Milli-Q water. The five experimental groups in the study were (1) control - no medicament, (2) medicament containing triamcinolone and demeclocycline (T&D) and occluded apex, (3) T&D paste and patent apex, (4) T&D + calcium hydroxide (Ca(OH)2) occluded apex, and (5) T&D + Ca(OH)2 and patent apex. The triamcinolone and demeclocycline concentrations were measured with solid-phase extraction and ultra-high performance liquid chromatography-mass spectrometry, after 1, 3, 8, and 24 h, and after 1 week. Results: Most of the triamcinolone and demeclocycline diffused through the apical foramen, with sparse diffusion through the dentinal tubules. The T&D paste mixed with Ca(OH)2 in equal amounts showed greater than the expected 50% reduction in the diffusion of triamcinolone and demeclocycline from mass dilution alone (89% and 80%, respectively). Conclusions: These results stress the importance of maintaining apical patency, for allowing diffusion of active components of the drugs to target tissues in the periapical environment.

Risk Factors Associated with Falls and Fractures Following Prescription of Opioids Among Privately Insured Patients with Osteoarthritis.

Background: While prior research has shown that patients with osteoarthritis (OA) who are prescribed opioids have higher rates of falls and fractures following drug initiation, there is a limited body of work establishing a comprehensive model of factors that influence the risk of falls or fractures among these patients. Objective: Opioids are associated with negative clinical outcomes, including increased risk of falls and fractures. This study assessed the frequency, treatment characteristics, and risk factors associated with falls or fractures among patients with OA taking opioids. Methods: Optum Healthcare Solutions, Inc data (January 2012-March 2017) were used to identify patients over 18 with at least 2 diagnoses of hip and/or knee OA, and at least 90 days' supply of opioids. Patients with cancer were excluded. Falls or fractures outcomes were assessed in the 36-month follow-up period after the date of the first opioid prescription after first OA diagnosis. Demographic, treatment, and clinical characteristics associated with falls or fractures were assessed using logistic regression. Results: Of 16 663 patients meeting inclusion criteria, 3886 (23%) had at least 1 fall or fracture during follow-up. Of these 3886 patients, 1349 (35%) had at least 1 fall with an average of 3 fall claims, and 3299 (85%) patients had at least 1 fracture with an average of 8 claims during follow-up. Spine (15.8%) and hip (12.5%) fractures were most common. Median time to fall or fracture was 18.6 and 13.9 months, respectively. Significant (P<.05) risk factors associated with at least 1 fall or fracture during the follow-up period included alcohol use (odds ratio [OR], 3.41), history of falling (OR, 2.19), non-tramadol opioid use (OR, 1.31), age (OR, 1.03), benzodiazepine use (OR, 1.21), and at least 1 osteoporosis diagnosis (OR, 2.06). Discussion: This study is among only a few that clearly identifies the substantial impact and frequency of falls and fractures associated with prescribing non-tramadol opioids to patients with OA. Findings suggest that fall or fracture risks need to be considered when managing OA pain with opioids. Conclusion: Falls and fractures impose a major clinical burden on patients prescribed opioids for OA-related pain management. Falls or fracture risks should be an important consideration in the ongoing treatment of patients with OA.

Study protocol for the evaluation of Fear-Less: a stepped-care program for fear of cancer recurrence in survivors with early-stage disease.

BACKGROUND: Fear of cancer recurrence (FCR) is a significant unmet need amongst cancer survivors and is consistently associated with psychological distress and impaired quality of life. Psychological interventions for FCR, such as ConquerFear, have demonstrated efficacy in reducing FCR and improving emotional wellbeing. Unfortunately, there are barriers to the uptake of evidence-based FCR treatments in clinical practice. A stepped-care FCR treatment model may overcome these barriers and has demonstrated potential in people with advanced melanoma. This study aims to evaluate the acceptability, feasibility, and impact of a stepped-care FCR treatment model (Fear-Less) in people with other cancer types, who have completed treatment with curative intent. METHODS: Sixty people with early-stage cancer (defined as individuals who have received treatment with curative intent and with no metastatic disease) will be screened for FCR using the Fear of Cancer Recurrence Inventory-Short Form (FCRI-SF). Individuals reporting moderate FCR (FCRI-SF between 13 and 21) will be offered a clinician-guided self-management resource; those reporting high FCR (FCRI-SF ≥ 22) will be offered individual therapy according to the ConquerFear protocol. Participants will complete purpose-built evaluation surveys assessing their FCR screening and intervention experiences. Clinicians will also complete a survey regarding their experiences of the treatment model. Fear-Less will be evaluated in terms of (1) acceptability (i.e., patient and clinician experience), (2) feasibility (i.e., referral uptake, treatment adherence, and time taken to screen and deliver interventions), and (3) impact (i.e., pre- to post-intervention FCR changes). DISCUSSION: The Fear-Less stepped-care model is a novel framework for screening FCR and stratifying survivors to the appropriate level of treatment. Our study will provide an indication of whether Fear-Less is a feasible and acceptable FCR model of care amongst survivors with early-stage disease and inform further investigations of this model. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR); ACTRN12622000818730 .

All-Cause Health Care and Work Loss Burden Associated With Nonsteroidal Anti-Inflammatory Drug and Opioid Treatment in Employed Patients With Osteoarthritis.

INTRODUCTION: This study estimated all-cause health care resource utilization (HRU) and costs and work loss outcomes associated with pain management of employed patients with osteoarthritis of the hip and/or knee. METHODS: Optum Health Care Solutions data were analyzed for employed patients prescribed nonsteroidal anti-inflammatory drugs, tramadol, or nontramadol opioids following diagnoses of osteoarthritis of the hip and/or knee. A pre-post design was used to evaluate changes in all-cause HRU and costs, and work loss days and associated costs. RESULTS: Costs rose for patients in all three cohorts (up to 198.3% for health care costs [tramadol] and up to 178.7% for work loss costs [tramadol]). Greatest increases in all-cause HRU included inpatient visits (237.9% [nonsteroidal anti-inflammatory drugs]; 600% [tramadol]). CONCLUSIONS: Study results provide evidence of increases in all-cause HRU and costs and work loss days and associated costs.

Association between staff turnover and nursing home quality - evidence from payroll-based journal data.

BACKGROUND: Staff turnover is considered an important indicator of nursing home quality. We used auditable staffing data from the Centers for Medicare & Medicaid Services (CMS) Payroll-Based Journal (PBJ) system to calculate turnover measures for nurse staff and administrators and examined the relationship between turnover and nursing home quality. METHODS: Our analyses included data from 13,631 nursing homes that submitted complete staffing data through PBJ for 2018Q3 - 2019Q4. We identified turnover based on gaps in days worked by eligible employees, allowing us to calculate turnover measures that do not depend on termination dates reported by nursing homes, which are not captured in PBJ. We linked staff turnover measures to nursing home quality measures and star ratings published on CMS' Care Compare website in January 2020 and examined the relationship between turnover and quality of care. We used ordinary least squared models for continuous outcomes and ordered logit models for categorical outcomes, controlling for facility, and county characteristics. RESULTS: Mean annual turnover rates were about 44% for RNs and 46% for total nurse staff. On average, there was one administrator leaving each nursing home during this period although about half of nursing homes had no administrator turnover. Turnover rates varied greatly across nursing homes. For-profit and larger nursing homes had higher turnover rates. Higher turnover was consistently associated with lower quality of care. CONCLUSIONS: Our study highlights the importance of staff turnover due to its relationship to nursing home quality. In January 2022, CMS started posting turnover measures on Care Compare to allow consumers to use this information in their assessment of nursing home quality and to motivate nursing homes to implement innovative strategies to retain staff. While these actions are challenging, they are nonetheless warranted for improving the quality of care for nursing home residents.

Drug utilization, clinical and economic outcomes of patients with osteoarthritis of the hip and/or knee treated with long-term use of traditional NSAIDs, topical NSAIDs, and COX-2 inhibitors.

OBJECTIVES: To describe and compare baseline characteristics, healthcare and drug utilization, and negative clinical outcomes of commercially-insured patients diagnosed with OA of the hip and/or knee who initiated treatment on traditional oral NSAIDs (tNSAIDs), topical NSAIDs, or cyclooxygenase-2 inhibitors (COX-2s). METHODS: A commercial claims database (1/2012-3/2017) was used to identify patients ≥18 years old, with ≥2 diagnoses of hip and/or knee OA, and ≥90 days supply of NSAIDs. Patients were assigned to cohorts based on the type of NSAID initially prescribed and observed in the 6 months before (baseline) and 36 months after (follow-up) the date of their first NSAID prescription after the first OA diagnosis. Analyses estimated baseline demographic and clinical characteristics and follow-up period drug utilization. Logistic regressions assessed the risk of gastrointestinal (GI) and acute renal failure (ARF) events. RESULTS: tNSAIDs were the most frequently prescribed treatment. During the follow-up period, less than 15% of patients prescribed tNSAIDs switched to either COX-2s or topical NSAIDs and 37% of patients prescribed a COX-2 and 56% of patients prescribed a topical NSAID switched to tNSAIDs. GI and ARF events during the follow-up period ranged from 7.3-8.1% and 8.0-11.0%, respectively, across cohorts. The tNSAIDs and COX-2s cohorts had increased risk of both types of events relative to patients prescribed topical NSAIDs, controlling for other characteristics. CONCLUSIONS: Analyses characterize the long-term real-world utilization of NSAIDs and associated outcomes for patients with OA of the hip and/or knee. Study results highlight the likelihood of switching and the risk of negative clinical outcomes associated with long-term use.

Gender and Social Inequalities in Awareness of Coronary Artery Disease in European Countries.

Coronary artery disease (CAD) is the single leading cause of death in Europe and the most common form of cardiovascular disease. Little is known about awareness in the European population. A cross-sectional telephone survey of 2609 individuals from six European countries was conducted to gather information on perceptions of CAD, risk factors, preventive measures, knowledge of heart attack symptoms and ability to seek emergency medical care. Level of awareness was compared according to gender, age, socioeconomic status (SES) and educational level. Women were approximately five times less likely than men to consider heart disease as a main health issue or leading cause of death (OR = 0.224, 95% CI: 0.178-0.280, OR = 0.196, 95% CI: 0.171-0.226). Additionally, women were significantly less likely to have ever had a cardiovascular screening test (OR = 0.515, 95% CI: 0.459-0.578). Only 16.3% of men and 15.3% of women were able to spontaneously identify the main symptoms of a heart attack. Almost half of the sample failed to state that they would call emergency services in case of a cardiac event. Significant differences according to age, SES and education were found for many indicators amongst both men and women. Development of a European strategy targeting improved awareness of CAD and reduced gender and social inequalities within the European population is warranted.

Clinical and economic burden of prescribing tramadol and other opioids for patients with osteoarthritis in a commercially insured population in the United States.

ABSTRACT: In 2019, the American College of Rheumatology conditionally recommended tramadol and conditionally recommended against nontramadol opioids for patients with hip and knee osteoarthritis. Although tramadol is known to be less prone to opioid use disorders, little is known about the differing magnitude of negative clinical outcomes, health care resource utilization, and costs of tramadol relative to nontramadol opioids. Administrative claims records for commercially insured patients with osteoarthritis who were prescribed opioids were used to compare clinical and cost outcomes during a 3-year follow-up period by conducting a pre-post analysis and a matched case-cohort analysis. Data for 14,491 patients were analyzed: 4048 (28%) were initiated on tramadol, and 10,443 (72%) were initiated on nontramadol opioids. After matching, 4048 patients per cohort were analyzed. In each empirical analysis, tramadol patients did develop opioid use disorders; however, opioid use disorder rates were 3.5-fold higher in the nontramadol cohort (1.2% vs 4.2%). In addition, rates of other opioid-related clinical outcomes (falls, fractures, nausea, fatigue, and constipation) were also directionally lower among the tramadol cohort, although quantitatively similar (<5% difference) to the nontramadol cohort. Finally, in both analyses, the nontramadol cohort incurred higher levels of inpatient and emergency department visits and all-cause costs during the 3-year follow-up period. However, tramadol patients incur a higher incremental change (+$24,013) in costs relative to their pretreatment baseline compared with nontramadol (+$18,191). These real-world findings demonstrated lower risks with tramadol relative to other opioids, albeit risks and increased health care costs were present with tramadol, highlighting the need for further strategies to improve outcomes.

A harm reduction model to assess the impact of new treatments for pain over standard of care among patients with osteoarthritis.

BACKGROUND: Osteoarthritis (OA) affects millions of adults in the United States and can result in substantial pain, functional impairment, and significant clinical and economic burden. To manage chronic pain associated with OA, treatment guidelines recommend a variety of pharmacologic treatments, including traditional oral nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors (COX-2s), and opioids. While these drug treatments can be effective at pain management, they are also associated with significant clinical and economic burden. New treatments for chronic pain among patients with OA of the hip and/or knee have the potential to reduce the occurrence of such negative clinical outcomes, including cardiovascular events, renal events, and opioid use disorder (OUD), thereby reducing health care resource use (HRU) and medical costs. OBJECTIVE: To develop a harm reduction model (HRM) to assess potential reductions of negative clinical outcomes, HRU, and medical costs associated with the use of new treatments in place of oral NSAIDs, tramadol, and non-tramadol opioids among patients with OA of the hip and/or knee in the United States. METHODS: The HRM model integrated findings from the literature and inputs from a variety of sources, along with assumptions regarding potential ability of new treatments to replace existing treatments and market penetration into a unified framework to estimate outcomes and costs. The model outputs included estimated per-patient and population-level reductions in negative clinical outcomes associated with prescribing new treatments in place of oral NSAIDs or opioids along with number needed to treat (NNT) associated with new treatments. The model assumed that new treatments will primarily be used in place of non-tramadol opioids, but more modest adoption in place of oral NSAIDs and tramadol. RESULTS: Among patients with OA of the hip and/or knee who were prescribed oral NSAIDs, tramadol, or non-tramadol opioids for chronic use (≥ 90 days), the HRM estimated total cost savings of $3.8 billion, $5.1 billion, and $29.9 billion, respectively, from prescribing new treatments for OA pain over a 36-month period. The reduced economic burden was driven by significant reductions in the incidence of negative clinical outcomes. Estimates of the NNT to avoid a negative clinical event related to NSAID and opioid treatment initiation were low for most outcomes. Estimates of NNT associated with NSAID use ranged from 4 to 17 patients, depending on outcome, and estimates of NNT associated with opioid use was 35 non-tramadol and 134 tramadol patients for OUD and ranged from 6 to 21 patients for the other clinical outcomes, depending on treatment and outcome. CONCLUSIONS: Results from the HRM suggest that prescribing new treatments in place of oral NSAIDs and/or opioids for OA pain results in a potentially substantial reduction in patients experiencing negative clinical outcomes and reductions in all-cause HRU and costs. DISCLOSURES: This study was sponsored by Pfizer and Eli Lilly and Company. Silverman was a paid consultant to Pfizer and Eli Lilly and Company in connection with this study. Beck and Schepman are employees of Pfizer with stock and/or stock options. Robinson is an employee and minor stockholder of Eli Lilly and Company. Rice, White, and Fernan are employees of the Analysis Group, who were paid consultants to Pfizer and Eli Lilly and Company for this study and development of the manuscript.

Beyond a Zero-Sum Game: How Does the Impact of COVID-19 Vary by Gender?

Epidemics and pandemics, like COVID-19, are not gender neutral. Much of the current work on gender, sex, and COVID-19, however, has seemed implicitly or explicitly to be attempting to demonstrate that either men or women have been hardest hit, treating differences between women and men as though it is not important to understand how each group is affected by the virus. This approach often leaves out the effect on gender and sexual minorities entirely. Believing that a more nuanced approach is needed now and for the future, we brought together a group of gender experts to answer the question: how are people of different genders impacted by COVID-19 and why? Individuals working in women's, men's, and LGBTQ health and wellbeing wrote sections to lay out the different ways that women, men, and gender and sexual minorities are affected by COVID-19. We demonstrate that there is not one group "most affected," but that many groups are affected, and we need to move beyond a zero-sum game and engage in ways to mutually identify and support marginalized groups.

Chemical Composition, Antibacterial Activity, and Antibiotic Potentiation of Boswellia sacra Flueck. Oleoresin Extracts from the Dhofar Region of Oman.

The emergence of MDR bacterial pathogens has directed antibiotic discovery research towards alternative therapies and traditional medicines. Boswellia sacra oleoresin (frankincense) was used to treat bacterial infections in traditional Arabian and Asian healing systems for at least 1000 years. Despite this, B. sacra extracts have not been rigorously tested for inhibitory activity against gastrointestinal pathogens or bacterial triggers of autoimmune diseases. Solvent extracts were prepared from Boswellia sacra oleoresins obtained from three regions near Salalah, Oman. MIC values were quantified against gastrointestinal pathogens and bacterial triggers of selected autoimmune diseases by disc diffusion and broth dilution methods. The antibacterial activity was also evaluated in combination with conventional antibiotics, and the class of interaction was determined by ΣFIC analysis. Isobolograms were used to determine the optimal ratios for synergistic combinations. Toxicity was evaluated by ALA and HDF cell viability bioassays. The phytochemical composition of the volatile components of all extracts was identified by nontargeted GC-MS headspace analysis. All methanolic extracts inhibited the growth of all of the bacteria tested, although the extracts prepared using Najdi oleoresin were generally more potent than the Sahli and Houjari extracts. Combinations of the methanolic B. sacra extracts and conventional antibiotics were significantly more effective in inhibiting the growth of several bacterial pathogens. In total, there were 38 synergistic and 166 additive combinations. Approximately half of the synergistic combinations contained tetracycline. All B. sacra extracts were nontoxic in the ALA and HDF cell viability assays. Nonbiased GC-MS headspace analysis of the methanolic extracts putatively identified a high diversity of monoterpenoids, with particularly high abundances of α-pinene. The antibacterial activity and lack of toxicity of the B. sacra extracts indicate their potential in the treatment and prevention of gastrointestinal and autoimmune diseases. Furthermore, the extracts potentiated the activity of several conventional antibiotics, indicating that they may contain resistance-modifying compounds.

The association of nursing home quality ratings and spread of COVID-19.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has severely affected nursing home residents. Given the continued high incidence of COVID-19, and the likelihood that new variants and other infectious agents may cause future outbreaks, we sought to understand the relationship of nursing home quality ratings and measures of COVID-19 outbreak severity and persistence. DESIGN: We analyzed nursing home facility-level data on COVID-19 cases and deaths, county-level COVID-19 rates, and nursing home data from the Centers for Medicare & Medicaid Services (CMS), including ratings from the CMS Nursing Home Five-Star Quality Rating System. We used regression analysis to examine the association between star ratings and cumulative COVID-19 incidence and mortality as well as persistent high resident incidence. SETTING: All nursing homes in the CMS COVID-19 Nursing Home Dataset reporting data that passed quality assurance checks for at least 20 weeks and that were included in the January 2021 Nursing Home Care Compare update. PARTICIPANTS: Residents of the included nursing homes. MEASUREMENTS: Cumulative resident COVID-19 incidence and mortality through January 10, 2021; number of weeks with weekly resident incidence of COVID-19 in the top decile nationally. RESULTS: As of January 10, 2021, nearly all nursing homes (93.6%) had reported at least one case of COVID-19 among their residents, more than three-quarters (76.9%) had reported at least one resident death, and most (83.5%) had experienced at least 1 week in the top decile of weekly incidence. In analyses adjusted for facility and county-level characteristics, we found generally consistent relationships between higher nursing home quality ratings and lower COVID-19 incidence and mortality, as well as with fewer high-incidence weeks. CONCLUSION: Nursing home quality ratings are associated with COVID-19 incidence, mortality, and persistence. Nursing homes receiving five-star ratings, for overall quality as well as for each domain, had lower COVID-19 rates among their residents.