Characterization and Management of Adverse Reactions in Patients With Advanced Endometrial Cancer Receiving Lenvatinib Plus Pembrolizumab.

BACKGROUND: Lenvatinib plus pembrolizumab significantly improved efficacy compared with chemotherapy in patients with advanced endometrial cancer (aEC) regardless of microsatellite instability status or histologic subtype, who had disease progression following prior platinum-based therapy, in Study-309/KEYNOTE-775. The safety profile of the combination was generally consistent with that of each monotherapy drug and of the combination in patients with endometrial cancer and other solid tumors. Given the medical complexity of patients with aEC, this paper aims to characterize key adverse reactions (ARs) of the combination treatment and review management strategies, providing a guide for AR management to maximize anticancer benefits and minimize treatment discontinuation. MATERIALS AND METHODS: In Study-309/KEYNOTE-775, patients received lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously every 3 weeks) or chemotherapy (doxorubicin or paclitaxel). The incidence and median time to the first onset of ARs, dose modifications, and concomitant medications are described. Key ARs characterized include hypothyroidism, hypertension, fatigue, diarrhea, musculoskeletal disorders, nausea, decreased appetite, vomiting, stomatitis, weight decreased, proteinuria, and palmar-plantar erythrodysesthesia syndrome. RESULTS: As expected, the most common any-grade key ARs included: hypothyroidism, hypertension, fatigue, diarrhea, and musculoskeletal disorders. Grades 3-4 key ARs with incidence ≥10% included: hypertension, fatigue, and weight decreased. Key ARs first occurred within approximately 3 months of treatment initiation. AR management strategies consistent with the prescribing information and the study protocol are discussed. CONCLUSION: Successful AR management strategies for lenvatinib plus pembrolizumab include education of the patient and entire treatment team, preventative measures and close monitoring, and judicious use of dose modifications and concomitant medications. CLINICALTRIALS.GOV ID: NCT03517449.

Drug persistence in patients with rheumatic and musculoskeletal diseases during a major economic crisis: results from a nationwide cross-sectional online survey.

To evaluate the drug persistence in patients with rheumatic and musculoskeletal diseases (RMDs) during the current economic crisis in Lebanon and to estimate predictors of persistence. A nationwide multicentric cross-sectional study using an online questionnaire was conducted in Lebanon with patients with chronic inflammatory rheumatic diseases (CIRDs) and non-inflammatory RMDs controls between July and October 2022. Disease-modifying antirheumatic drugs (DMARDs) were categorized as conventional synthetic (cs), biological (b), subcutaneous (SC) or intravenous (IV), and targeted synthetic (ts). Persistence was defined as "number of tablets or injections taken during the past month versus prescribed". The percentage of patients who discontinued or changed treatment due to cost or non-availability was reported. Factors associated with persistence were identified using multivariable linear regression. The study included 317 patients with RMDs (286 CIRDs); mean age 49.5 years, 68% females, 58% reporting currently low economic level. Persistence at one month was low for tsDMARDs (36%) and bDMARDs (SC55%, IV63%), and acceptable for csDMARDs (88%). A persistence ≥80% was found in 23.3% of patients on tsDMARDs, 42.9% on SC bDMARDs, 45.0% on IV bDMARDs, and 74.7% on csDMARDs. During the past 6 months, 55.8% of CIRD patients discontinued or changed treatment due to non-availability (45.3%) or cost (21.2%). Persistence was positively associated with finding alternative sources such as buying abroad (36%), depending on friends or families abroad (20%), charities (10%), and negatively associated with unemployment and low financial status. Persistence was significantly compromised for essential antirheumatic drugs and was mostly driven by treatment unavailability and cost.

Ketorolac Injections for Musculoskeletal Conditions: A Narrative Review.

Musculoskeletal conditions of the upper and lower extremities are commonly treated with corticosteroid injections. Ketorolac, a parenteral nonsteroidal anti-inflammatory drug, represents an alternative injectant for common shoulder, hip, and knee conditions. A review of the current literature was conducted on the efficacy of ketorolac injection in musculoskeletal diseases. Several studies support the use and efficacy of ketorolac injection in subacromial bursitis, adhesive capsulitis, and hip and knee osteoarthritis. Given the systemic effects of glucocorticoid injections, ketorolac may be a safe and effective alternative in patients with musculoskeletal disease. However, more evidence is required to better understand the effects ketorolac has on the human body during inflammatory processes.

Ethnobotany and phytochemistry of plants used to treat musculoskeletal disorders among Skaw Karen, Thailand.

CONTEXT: Musculoskeletal system disorders (MSD) are prevalent around the world affecting the health of people, especially farmers who work hard in the field. Karen farmers use many medicinal plants to treat MSD. OBJECTIVE: This study collects traditional plant-based remedies used by the Skaw Karen to treat MSD and evaluates their active phytochemical compounds. MATERIALS AND METHODS: The ethnobotanical study was conducted in six Karen villages in Chiang Mai province using semi-structured interviews were of 120 informants. The data were analyzed using ethnobotanical indices including use values (UV), choice value (CV), and informant consensus factor (ICF). Consequently, the 20 most important species, according to the indices, were selected for phytochemical analysis using LC-MS/MS. RESULTS: A total of 3731 use reports were obtained for 139 species used in MSD treatment. The most common ailments treated with those plants were muscular pain. A total of 172 high-potential active compounds for MSD treatment were identified. Most of them were flavonoids, terpenoids, alkaloids, and steroids. The prevalent phytochemical compounds related to treat MSD were 9-hydroxycalabaxanthone, dihydrovaltrate, morroniside, isoacteoside, lithocholic acid, pomiferin, cucurbitacin E, leonuriside A, liriodendrin, and physalin E. Sambucus javanica Reinw. ex Blume (Adoxaceae), Betula alnoides Buch.-Ham. ex D.Don (Betulaceae), Blumea balsamifera (L.) DC. (Asteraceae), Plantago major L. (Plantaginaceae) and Flacourtia jangomas (Lour.) Raeusch. (Salicaceae) all had high ethnobotanical index values and many active compounds. DISCUSSION AND CONCLUSIONS: This study provides valuable information, demonstrating low-cost medicine plants that are locally available. It is a choice of treatment for people living in remote areas.

Influence of the COVID-19 Pandemic on Medical Management and on Healthcare Delivery of Immune-Mediated Rheumatic and Musculoskeletal Diseases during the First Pandemic Period February to July 2020: A Systematic Review.

(1) Background and Objectives: The COVID-19 pandemic influenced the management of patients with immune-mediated rheumatic and musculoskeletal diseases (imRMDs) in various ways. The goal of our systematic review was to determine the influence of the first period of the COVID-19 pandemic (February 2020 to July 2020) on the management of imRMDs regarding the availability of drugs, adherence to therapy and therapy changes and on healthcare delivery. (2) Materials and Methods: We conducted a systematic literature search of PubMed, Cochrane and Embase databases (carried out 20-26 October 2021), including studies with adult patients, on the influence of the COVID-19 pandemic on the management of imRMDs. There were no restrictions regarding to study design except for systematic reviews and case reports that were excluded as well as articles on the disease outcomes in case of SARS-CoV-2 infection. Two reviewers screened the studies for inclusion, and in case of disagreement, a consensus was reached after discussion. (3) Results: A total of 5969 potentially relevant studies were found, and after title, abstract and full-text screening, 34 studies were included with data from 182,746 patients and 2018 rheumatologists. The non-availability of drugs (the impossibility or increased difficulty to obtain a drug), e.g., hydroxychloroquine and tocilizumab, was frequent (in 16-69% of patients). Further, medication non-adherence was reported among patients with different imRMDs and between different drugs in 4-46% of patients. Changes to preexisting medication were reported in up to 33% of patients (e.g., reducing the dose of steroids or the cessation of biological disease-modifying anti-rheumatic drugs). Physical in-office consultations and laboratory testing decreased, and therefore, newly implemented remote consultations (particularly telemedicine) increased greatly, with an increase of up to 80%. (4) Conclusions: The COVID-19 pandemic influenced the management of imRMDs, especially at the beginning. The influences were wide-ranging, affecting the availability of pharmacies, adherence to medication or medication changes, avoidance of doctor visits and laboratory testing. Remote and telehealth consultations were newly implemented. These new forms of healthcare delivery should be spread and implemented worldwide to routine clinical practice to be ready for future pandemics. Every healthcare service provider treating patients with imRMDs should check with his IT provider how these new forms of visits can be used and how they are offered in daily clinical practice. Therefore, this is not only a digitalization topic but also an organization theme for hospitals or outpatient clinics.

EULAR points to consider for therapeutic drug monitoring of biopharmaceuticals in inflammatory rheumatic and musculoskeletal diseases.

OBJECTIVE: To develop EULAR points-to-consider for therapeutic drug monitoring (TDM) of biopharmaceuticals in inflammatory rheumatic and musculoskeletal diseases (RMDs). METHODS: The points-to-consider were developed in accordance with EULAR standardised operation procedures by a multidisciplinary task force from eight European countries, based on a systematic literature review and expert consensus. Level of evidence and strength of the points-to-consider were determined, and mean levels of agreement among the task force were calculated using a 10-point rating scale. RESULTS: Six overarching principles and 13 points-to-consider were formulated. The level of agreement among the task force for the overarching principles and points-to-consider ranged from 8.4 to 9.9.The overarching principles define TDM and its subtypes, and reinforce the underlying pharmacokinetic/pharmacodynamic principles, which are relevant to all biopharmaceutical classes. The points-to-consider highlight the clinical utility of the measurement and interpretation of biopharmaceutical blood concentrations and antidrug antibodies in specific clinical scenarios, including factors that influence these parameters. In general, proactive use of TDM is not recommended but reactive TDM could be considered in certain clinical situations. An important factor limiting wider adoption of TDM is the lack of both high quality trials addressing effectiveness and safety of TDM and robust economic evaluation in patients with RMDs. Future research should focus on providing this evidence, as well as on further understanding of pharmacokinetic and pharmacodynamic characteristics of biopharmaceuticals. CONCLUSION: These points-to-consider are evidence-based and consensus-based statements for the use of TDM of biopharmaceuticals in inflammatory RMDs, addressing the clinical utility of TDM.

Biochemical Markers of Musculoskeletal Health and Aging to be Assessed in Clinical Trials of Drugs Aiming at the Treatment of Sarcopenia: Consensus Paper from an Expert Group Meeting Organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the Centre Académique de Recherche et d'Expérimentation en Santé (CARES SPRL), Under the Auspices of the World Health Organization Collaborating Center for the Epidemiology of Musculoskeletal Conditions and Aging.

In clinical trials, biochemical markers provide useful information on the drug's mode of action, therapeutic response and side effect monitoring and can act as surrogate endpoints. In pharmacological intervention development for sarcopenia management, there is an urgent need to identify biomarkers to measure in clinical trials and that could be used in the future in clinical practice. The objective of the current consensus paper is to provide a clear list of biochemical markers of musculoskeletal health and aging that can be recommended to be measured in Phase II and Phase III clinical trials evaluating new chemical entities for sarcopenia treatment. A working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) proposed classifying biochemical markers into 2 series: biochemical markers evaluating musculoskeletal status and biochemical markers evaluating causal factors. For series 1, the group agreed on 4 biochemical markers that should be assessed in Phase II or Phase III trials (i.e., Myostatin-Follistatin, Brain Derived Neurotrophic Factor, N-terminal Type III Procollagen and Serum Creatinine to Serum Cystatin C Ratio - or the Sarcopenia Index). For series 2, the group agreed on 6 biochemical markers that should be assessed in Phase II trials (i.e., the hormones insulin-like growth factor-1 (IGF-I), dehydroepiandrosterone sulphate, and cortisol, and the inflammatory markers C-reactive protein (CRP), interleukin-6 and tumor necrosis factor-α), and 2 in Phase III trials (i.e., IGF-I and CRP). The group also proposed optional biochemical markers that may provide insights into the mode of action of pharmacological therapies. Further research and development of new methods for biochemical marker assays may lead to the evolution of these recommendations.

[On the use of type I tropocollagen for local injection therapy of spine, upper and lower extremity disorders].

A meeting of Interdisciplinary Expert Panel with leading specialists in the field of orthopedics/traumatology, surgery, rheumatology, and neurology was held in Moscow on February 10, 2023. The purpose of the meeting was to discuss the current status of local injection therapy (LIT) in Russia and the rationale behind the use of collagen-based products for various musculoskeletal disorders. The experts considered the following issues: (1) General contraindications to the use of medical products based on tropocollagen as well as an algorithm for actions in case of adverse events; (2) Guidelines regarding LIT in general and LIT using tropocollagen in particular, including in combination with other LIT products; (3) Particular indications and approaches to the treatment of patients with abnormal changes in appendicular joints and spine with damage to both intra-articular structures and periarticular soft tissue.

Safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine (COVAX) physician-reported registry.

OBJECTIVES: To describe the safety of vaccines against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal disease (I-RMD). METHODS: Physician-reported registry of I-RMD and non-inflammatory RMD (NI-RMDs) patients vaccinated against SARS-CoV-2. From 5 February 2021 to 27 July 2021, we collected data on demographics, vaccination, RMD diagnosis, disease activity, immunomodulatory/immunosuppressive treatments, flares, adverse events (AEs) and SARS-CoV-2 breakthrough infections. Data were analysed descriptively. RESULTS: The study included 5121 participants from 30 countries, 90% with I-RMDs (n=4604, 68% female, mean age 60.5 years) and 10% with NI-RMDs (n=517, 77% female, mean age 71.4). Inflammatory joint diseases (58%), connective tissue diseases (18%) and vasculitis (12%) were the most frequent diagnostic groups; 54% received conventional synthetic disease-modifying antirheumatic drugs (DMARDs), 42% biological DMARDs and 35% immunosuppressants. Most patients received the Pfizer/BioNTech vaccine (70%), 17% AstraZeneca/Oxford and 8% Moderna. In fully vaccinated cases, breakthrough infections were reported in 0.7% of I-RMD patients and 1.1% of NI-RMD patients. I-RMD flares were reported in 4.4% of cases (0.6% severe), 1.5% resulting in medication changes. AEs were reported in 37% of cases (37% I-RMD, 40% NI-RMD), serious AEs in 0.5% (0.4% I-RMD, 1.9% NI-RMD). CONCLUSION: The safety profiles of SARS-CoV-2 vaccines in patients with I-RMD was reassuring and comparable with patients with NI-RMDs. The majority of patients tolerated their vaccination well with rare reports of I-RMD flare and very rare reports of serious AEs. These findings should provide reassurance to rheumatologists and vaccine recipients and promote confidence in SARS-CoV-2 vaccine safety in I-RMD patients.

Risk and prognosis of SARS-CoV-2 infection and vaccination against SARS-CoV-2 in rheumatic and musculoskeletal diseases: a systematic literature review to inform EULAR recommendations.

OBJECTIVES: Perform a systematic literature review (SLR) on risk and prognosis of SARS-CoV-2 infection and vaccination against SARS-CoV-2 in patients with rheumatic and musculoskeletal diseases (RMDs). METHODS: Literature was searched up to 31 May 2021, including (randomised) controlled trials and observational studies with patients with RMD. Pending quality assessment, data extraction was performed and risk of bias (RoB) was assessed. Quality assessment required provision of (1) an appropriate COVID-19 case definition, and (2a) a base incidence (for incidence data) or (2b) a comparator, >10 cases with the outcome and risk estimates minimally adjusted for age, sex and comorbidities (for risk factor data). RESULTS: Of 5165 records, 208 were included, of which 90 passed quality assessment and data were extracted for incidence (n=42), risk factor (n=42) or vaccination (n=14). Most studies had unclear/high RoB. Generally, patients with RMDs do not face more risk of contracting SARS-CoV-2 (n=26 studies) or worse prognosis of COVID-19 (n=14) than individuals without RMDs. No consistent differences in risk of developing (severe) COVID-19 were found between different RMDs (n=19). Disease activity is associated with worse COVID-19 prognosis (n=2), possibly explaining the increased risk seen for glucocorticoid use (n=13). Rituximab is associated with worse COVID-19 prognosis (n=7) and possibly Janus kinase inhibitors (n=3). Vaccination is generally immunogenic, though antibody responses are lower than in controls. Vaccine immunogenicity is negatively associated with older age, rituximab and mycophenolate. CONCLUSION: This SLR informed the July 2021 update of the European Alliance of Associations for Rheumatology recommendations for the management of RMDs in the context of SARS-CoV-2.

Pain and Prescription Opioid Use Among US Construction Workers: Findings From the 2011‒2018 Medical Expenditure Panel Survey.

Objectives. To examine prescription opioid and nonopioid analgesic use among US construction workers and their associations with pain conditions and sociodemographic factors. Methods. We analyzed data for about 9000 (weighted 11.5 million per year) construction workers who responded to the Medical Expenditure Panel Survey from 2011 to 2018. We applied both descriptive statistics and multiple logistic regression procedures in the analyses. Results. An estimated 1.2 million (10.0%) of construction workers used prescription opioid analgesics annually. The adjusted odds of prescription opioid use were significantly higher for workers suffering from work-related injuries (adjusted odds ratio [AOR] = 3.82; 95% confidence interval [CI] = 2.72, 5.37), non‒work-related injuries (AOR = 3.37; 95% CI = 2.54, 4.46), and musculoskeletal disorders (AOR = 2.31; 95% CI = 1.80, 2.95) after we controlled for potential confounders. Adjusted odds of prescription opioid use were also higher among workers with poorer physical health (AOR = 1.95; 95% CI = 1.42, 2.69) or mental health disorders (AOR = 1.95; 95% CI = 1.41, 2.68). Conclusions. Work- and non‒work-related injuries and musculoskeletal disorders significantly increased prescription opioid use among construction workers. To prevent opioid use disorders, multipronged strategies should be approached. (Am J Public Health. 2022;112(S1):S77-S87. https://doi.org/10.2105/AJPH.2021.306510).

The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review.

BACKGROUND: Preclinical studies have shown a therapeutic role of the mechanistic/mammalian target of rapamycin complex 1 (mTORC1) inhibition with rapamycin and its analogues (rapalogues) on several age-related musculoskeletal disorders (MSKD). However, the applicability to humans of these findings is unknown. OBJECTIVE: To assess the efficacy of rapalogues on age-related MSKD in humans. METHODS: We conducted a systematic review according to the PRISMA guidelines. MEDLINE, EMBase, EMCare, and Cochrane Central Registry of Controlled Trials were searched for original studies examining the effects of rapalogues on outcomes linked to the age-related MSKD in humans. This review is registered in the PROSPERO database (University of New York; registration number CRD42020208167). RESULTS: Fourteen studies met the inclusion criteria and were analyzed. The effect of rapamycin and other rapalogues, including everolimus and temsirolimus, on bone, muscle and joints have been evaluated in humans; however, considerable variability concerning the subjects' age, inclusion criteria, and drug administration protocols was identified. In bone, the use of rapamycin is associated with a decrease in bone resorption markers dependent on osteoclastic activity. In muscle, rapamycin and rapalogues are associated with a reduction in muscle protein synthesis in response to exercise. In the context of rheumatoid arthritis, rapamycin and rapalogues have been associated with clinical improvement and a decrease in inflammatory activity. CONCLUSION: Although there are studies that have evaluated the effect of rapamycin and rapalogues on MSKD in humans, the evidence supporting its use is still incipient, and the clinical implication of these results on the development of osteoporosis, sarcopenia, or osteosarcopenia has not been studied, opening an interesting field for future research.

Substance P, A Promising Therapeutic Target in Musculoskeletal Disorders.

A large number of studies have focused on the role of substance P (SP) and the neurokinin-1 receptor (NK1R) in the pathogenesis of a variety of medical conditions. This review provides an overview of the role of the SP-NK1R pathway in the pathogenesis of musculoskeletal disorders and the evidence for its role as a therapeutic target for these disorders, which are major public health problems in most countries. To summarize, the brief involvement of SP may affect tendon healing in an acute injury setting. SP combined with an adequate conjugate can be a regenerative therapeutic option in osteoarthritis. The NK1R antagonist is a promising agent for tendinopathy, rheumatoid arthritis, and osteoarthritis. Research on the SP-NK1R pathway will be helpful for developing novel drugs for osteoporosis.

Contemporary Clinical Isolates of Staphylococcus aureus from Pediatric Osteomyelitis Patients Display Unique Characteristics in a Mouse Model of Hematogenous Osteomyelitis.

Osteomyelitis can result from the direct inoculation of pathogens into bone during injury or surgery or from spread via the bloodstream, a condition called hematogenous osteomyelitis (HOM). HOM disproportionally affects children, and more than half of cases are caused by Staphylococcus aureus. Laboratory models of osteomyelitis mostly utilize direct injection of bacteria into the bone or implantation of foreign material and therefore do not directly interrogate the pathogenesis of pediatric hematogenous osteomyelitis. In this study, we inoculated mice intravenously and characterized the resultant musculoskeletal infections using two strains isolated from adults (USA300-LAC and NRS384) and five new methicillin-resistant S. aureus isolates from pediatric osteomyelitis patients. All strains were capable of creating stable infections over 5 weeks, although the incidence varied. Micro-computed tomography (microCT) analysis demonstrated decreases in the trabecular bone volume fraction but little effect on bone cortices. Histological assessment revealed differences in the precise focus of musculoskeletal infection, with various mixtures of bone-centered osteomyelitis and joint-centered septic arthritis. Whole-genome sequencing of three new isolates demonstrated distinct strains, two within the USA300 lineage and one USA100 isolate. Interestingly, this USA100 isolate showed a distinct predilection for septic arthritis compared to the other isolates tested, including NRS384 and LAC, which more frequently led to osteomyelitis or mixed bone and joint infections. Collectively, these data outline the feasibility of using pediatric osteomyelitis clinical isolates to study the pathogenesis of HOM in murine models and lay the groundwork for future studies investigating strain-dependent differences in musculoskeletal infection.

Influence of COVID-19 pandemic on decisions for the management of people with inflammatory rheumatic and musculoskeletal diseases: a survey among EULAR countries.

OBJECTIVES: To investigate how the first wave of COVID-19 pandemic influenced decisions of rheumatologists and health professionals in rheumatology regarding the management of patients with inflammatory rheumatic and musculoskeletal diseases (RMDs). METHODS: An English-language questionnaire was developed by a EULAR working group and distributed via national rheumatology societies of EULAR countries, EMEUNET and individual working group members. Responses were collected using an online survey tool. Descriptive statistics were calculated. RESULTS: We analysed 1286 responses from 35/45 EULAR countries. Due to containment measures, 82% of respondents indicated cancellation/postponement of face-to-face visits of new patients (84% of them offering remote consultation) and 91% of follow-up visits (96% with remote consultation). The majority of respondents (58%) perceived that the interval between symptom onset and first rheumatological consultations was longer during containment restrictions than before. Treatment decisions were frequently postponed (34%), and the majority (74%) of respondents stated that it was less likely to start a biological disease modifying anti-rheumatic drug (DMARD)/targeted synthetic DMARD during the pandemic, mainly because of patients' fear, limited availability of screening procedures and decreased availability of rheumatological services. Use of (hydroxy)chloroquine (HCQ) and tocilizumab (TCZ) for the COVID-19 indication was reported by 47% and 42% of respondents, respectively, leading to a shortage of these drugs for RMDs indications according to 49% and 14% of respondents, respectively. CONCLUSION: Measures related to containment of COVID-19 pandemic led to a perceived delay between symptom onset and a first rheumatological visit, postponement of treatment decisions, and shortage of HCQ and TCZ, thereby negatively impacting early treatment and treat-to-target strategies.

Investigation of biofilm production and its association with genetic and phenotypic characteristics of OM (osteomyelitis) and non-OM orthopedic Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus is a primary pathogen of orthopedic infections. By mediating antimicrobial resistance, S. aureus biofilm plays an important role in the recalcitrance of orthopedic infections, especially for the intractable osteomyelitis (OM). This study investigated the relationship between biofilm production and various genetic or phenotypic characteristics among orthopedic S. aureus strains. METHODS: A total of 137 orthopedic S. aureus isolates were enrolled and divided into OM and non-OM groups. Biofilm production was evaluated using the crystal violet assay. Genetic and phenotypic characteristics including MRSA identification, MLST and spa typing, carriage of virulence genes, drug resistance, and patients' inflammatory responses indicators were characterized. The relationship between biofilm production and above-mentioned features was respectively analyzed among all isolates and compared between OM and non-OM isolates. RESULTS: Biofilm production presented no significant difference between OM (including 9 MRSA isolates) and non-OM (including 21 MRSA isolates) strains. We found that ST88, t377 and ST630-MSSA-t377 strains produced very strong biofilms, while MLST types of ST15, ST25, ST398, ST5, ST59 and spa types of t002, t2325, t437 tended to produce weaker biofilms. Strains with the following profiles produced stronger biofilms: fib(+)-hlgv(+)-lukED(+)-sei(-)-sem(-)-seo(-) for all isolates, sei(-)-sem(-)-seo(-) for OM isolates, and cna (+)-fib (+)-hlgv (+)-lukED (+)-seb(-)-sed(-) for non-OM isolates. In addition, not any single drug resistance was found to be related to biofilm production. We also observed that, among OM patients, strains with stronger biofilms caused weaker inflammatory responses. CONCLUSION: Some genetic or phenotypic characteristics of orthopedic strains were associated with biofilm production, and this association could be different among OM and non-OM strains. The results are of great significance for better understanding, evaluating and managing different kinds of biofilm-associated orthopedic infections, and provide potential targets for biofilm clearance.

The effect of music on pain and subjective experience in image-guided musculoskeletal corticosteroid injections: a randomized controlled trial.

PURPOSE: To investigate the role of music on subjects undergoing routine image-guided musculoskeletal corticosteroid injections and its effect on post-procedure pain and subjective overall experience. MATERIALS AND METHODS: This prospective study was IRB-approved and HIPAA-compliant. A total of 126 subjects referred for outpatient image-guided musculoskeletal corticosteroid injections were enrolled in the study and randomized into a music offered group ((+)MO) and a no music offered group ((-)MO). (+)MO subjects were given the opportunity to listen to music during their corticosteroid injection. All subjects were then given an anonymous survey on which they recorded their pre-procedural and post-procedural pain on a scale from 0 to 9 and rated their overall experience and how likely they were to recommend our department for musculoskeletal procedures on scales from 1 to 5. RESULTS: (+)MO subjects had significantly lower post-procedural pain (p = 0.013) and significantly greater decrease in pain (p = 0.031) compared to (-)MO subjects. Among the (+)MO subjects, there was no statistically significant difference in post-procedure pain (p = 0.34) or change in pain (p = 0.62) if music was accepted or declined. However, subjects who listened to music did have lower post-procedural pain compared to those who did not listen to music (p = 0.012), although the differences in the decrease of pain between the two groups did not quite reach statistical significance (p = 0.062). CONCLUSIONS: Playing music during image-guided musculoskeletal corticosteroid injections may reduce patients' post-procedure pain. Offering patients some measure of control over their procedure may be a factor that contributes to decreased post-procedure pain as well.

Acceptance and Commitment Therapy Delivered via a Mobile Phone Messaging Robot to Decrease Postoperative Opioid Use in Patients With Orthopedic Trauma: Randomized Controlled Trial.

BACKGROUND: Acceptance and commitment therapy (ACT) is a pragmatic approach to help individuals decrease avoidable pain. OBJECTIVE: This study aims to evaluate the effects of ACT delivered via an automated mobile messaging robot on postoperative opioid use and patient-reported outcomes (PROs) in patients with orthopedic trauma who underwent operative intervention for their injuries. METHODS: Adult patients presenting to a level 1 trauma center who underwent operative fixation of a traumatic upper or lower extremity fracture and who used mobile phone text messaging were eligible for the study. Patients were randomized in a 1:1 ratio to either the intervention group, who received twice-daily mobile phone messages communicating an ACT-based intervention for the first 2 weeks after surgery, or the control group, who received no messages. Baseline PROs were completed. Two weeks after the operative intervention, follow-up was performed in the form of an opioid medication pill count and postoperative administration of PROs. The mean number of opioid tablets used by patients was calculated and compared between groups. The mean PRO scores were also compared between the groups. RESULTS: A total of 82 subjects were enrolled in the study. Of the 82 participants, 76 (38 ACT and 38 controls) completed the study. No differences between groups in demographic factors were identified. The intervention group used an average of 26.1 (SD 21.4) opioid tablets, whereas the control group used 41.1 (SD 22.0) tablets, resulting in 36.5% ([41.1-26.1]/41.1) less tablets used by subjects receiving the mobile phone-based ACT intervention (P=.004). The intervention group subjects reported a lower postoperative Patient-Reported Outcome Measure Information System Pain Intensity score (mean 45.9, SD 7.2) than control group subjects (mean 49.7, SD 8.8; P=.04). CONCLUSIONS: In this study, the delivery of an ACT-based intervention via an automated mobile messaging robot in the acute postoperative period decreased opioid use in selected patients with orthopedic trauma. Participants receiving the ACT-based intervention also reported lower pain intensity after 2 weeks, although this may not represent a clinically important difference. TRIAL REGISTRATION: ClinicalTrials.gov NCT03991546; https://clinicaltrials.gov/ct2/show/NCT03991546.

Musculoskeletal Pain Medication Use in Middle Age and Older Adults in 15 European Countries and Israel.

BACKGROUND: The experience of musculoskeletal pain is widespread among adults and entails high costs to both individuals and society. Few studies look at disparities in pain management. AIMS: To examine factors associated with the presence of musculoskeletal pain and the use of pain medication use among individuals aged 50+. DESIGN: Cross-sectional analysis of data from the SHARE. PARTICIPANTS: 64,281 community-dwelling individuals in 15 European countries and Israel. METHODS: Bivariate analysis and logistic regression were used to identify factors associated with the presence of musculoskeletal pain and pain medication use. RESULTS: Among our population, the prevalence of musculoskeletal pain at the time of the survey was 40.1%. Women had more pain than men (odds ratio [OR] = 1.477, confidence interval [CI] = 1.428-1.528), those who were 60-69 years old had less pain than younger individuals (OR = 0.927, CI = 0.883-0.973), whereas those who were 80+ years old had more pain than younger individuals (OR = 1.280, CI = 1.199-1.367). About 50% of those with musculoskeletal pain take no medication to manage it. Predictors of pain medication use include male sex (OR = 1.468, CI = 1.389-1.553), more education (OR = 1.034, CI = 1.023-1.041), and better ability to cope economically (OR = 1.446, CI = 1.368-1.527). Those over 70 are less likely than younger individuals to be taking medication to manage their pain (70-79: OR = 0.822, CI = 0.761-0.887), (80+: OR = 0.619, CI = 0.566-0.677). CONCLUSIONS: Nurses should be aware of the association of education and income with pain-medication use, which suggests that pain medication use is less accessible to those with fewer resources. Pain is a significant public-health problem, and access to medicine deserves attention from nurses, healthcare workers and policymakers.

Utilization of Botulinum Toxin for Musculoskeletal Disorders.

Rehabilitation from musculoskeletal injuries is challenging with multiple intrinsic and extrinsic factors influencing athletes, conditions, and length of recovery. Multidisciplinary treatment strategies aim to address pathophysiology, mechanical, and psychosocial factors of injuries. An essential element in the recovery from musculoskeletal injuries is pain control and the return of physiologic function. There have been significant advancements in the understanding of pain and, therefore, new techniques and management strategies are being used. Botulinum neurotoxin (BoNT) has demonstrated valuable biopharmaceutical properties to provide neuromuscular blockade, which, in some cases, can help to return biomechanical and functional physiologic loss. There is developing literature in BoNT's ability to block pain in the treatment of painful musculoskeletal conditions. Critical analysis of the literature is necessary given the paucity of high-quality, evidence-based literature in the treatment of these conditions. This article reviews the utilization of BoNT in chronic exertional compartment syndrome, osteoarthritis, lateral epicondylosis, plantar fasciopathy, and myofascial pain syndrome.