A Bayesian model to analyse the association of comorbidities with biosimilar treatment retention in a non-medical switch scenario in patients with inflammatory rheumatic musculoskeletal diseases.

OBJECTIVES: To analyse clinical outcomes of a non-medical switch from originator adalimumab (ADA) to its ABP501 biosimilar (ABP) over 6 months in patients with inflammatory rheumatic musculoskeletal diseases (RMD) in relation to comorbidity as a risk factor for therapy discontinuation. METHODS: RMD patients switching from originator ADA to ABP were identified from a large routine database from October 2018 onwards. Documented clinical data at the time of non-medical switching (baseline), and at 3 and 6 months were collected. Comorbidities were represented by the Charlson Comorbidity Index (CCI) at baseline and patients were categorized based on CCI > 0. Differences in the ABP retention rate over 6 months between patients with CCI = 0 and patients with CCI > 0 were analysed using Bayesian exponential regression. RESULTS: A total of 111 patients with axial spondyloarthritis (n = 68), rheumatoid arthritis (n = 23) and psoriatic arthritis (n = 15), were identified, 74.8% of whom had continued treatment with ABP after 6 months, while a smaller proportion had either switched to another ADA biosimilar (10.8%), switched back to originator ADA (7.2%), switched to a different biologic (3.6%), or dropped out (3.6%). At baseline, a CCI > 0 was found in 38% of patients. Cardiovascular comorbidities (40%) were most prevalent followed by diseases of the skin (33%), the gastrointestinal tract (20%) and the eye (20%). ABP treatment was continued after 6 months in 74% of patients with CCI = 0 and in 76% with CCI > 0. Bayesian analysis showed only a small difference (months) in the APB continuation rate between groups (estimate 0.0012, 95% credible interval (CrI) -0.0337 to 0.0361). Adjusting for age, sex, and disease subtype revealed somewhat shorter retention rates for patients with CCI > 0, but the distribution of the difference included 0 (estimate -0.0689, 95% CrI -0.2246 to 0.0234). CONCLUSION: In a non-medical switch scenario of RMD patients, there was no evidence for a considerable difference in ABP retention rates over 6 months between comorbidity groups.

A Study on the Effectiveness of Musculoskeletal Corticosteroid Injections for Reducing Patient Symptom Scores in Primary Care Practice.

OBJECTIVES: To present data on the effectiveness of corticosteroid injections (CSI) in reducing symptom scores for musculoskeletal conditions in patients treated in an NHS primary care CSI service. The data will also examine whether adding local anaesthetic to the corticosteroid preparation affects the overall patient outcomes in symptom scores. METHODS: A Patient-reported outcomes (PRO) questionnaire was used to collect data. Patients were asked to complete the questionnaire post-CSI. Patients were asked to rate their symptoms on a score of 0-6 before and after their injection. Data were calculated using standard deviation and paired t-test to assess the effectiveness of CSI in reducing symptom scores. RESULTS: Overall, 172 patients (79.6%) reported an improvement in symptomatology post CSI. Improvements were seen across all injection sites. Of those taking medication for their symptoms, 73 patients (55.7%) reported that they were able to reduce their medication. Data did not suggest that adding local anaesthetic to the injectate resulted in better patient outcomes. Post-injection symptom scores were statistically similar across all clinicians. CONCLUSION: 83.7% of patients experienced a reduction in symptom scores post injection. Adding lidocaine to the injectate preparation did not result in any statistically significant improvement in patient outcome. Over half of the participants were able to reduce their medication post injection, which demonstrates this is a highly effective primary care service for treatment/management of some MSK conditions.

Ozone therapy in musculoskeletal medicine: a comprehensive review.

Musculoskeletal disorders encompass a wide range of conditions that impact the bones, joints, muscles, and connective tissues within the body. Despite the ongoing debate on toxicity and administration, ozone demonstrated promise in managing several musculoskeletal disorders, modulating pain and inflammation. A literature search was conducted. The research design, methods, findings, and conclusions of the studies were then examined to evaluate the physiological effects, clinical application, controversies, and safety of the application of ozone in musculoskeletal medicine. Ozone application demonstrates considerable therapeutic applications in the management of musculoskeletal disorders, including fractures, osteoarthritis, and chronic pain syndromes. Despite these advantages, studies have raised concerns regarding its potential toxicity and emphasized the importance of adhering to stringent administration protocols to ensure safety. Additionally, heterogeneities in patient reactions and hazards from oxidizing agents were observed. Given its anti-inflammatory and analgesic qualities, ozone therapy holds potential in the management of several musculoskeletal disorders. Additional high-quality research with long follow-up is required to refine indications, efficacy and safety profile. Finally, for wider clinical acceptability and utilization, the development of international recommendations is essential.

Challenges of designing and conducting cohort studies and clinical trials in populations of pregnant people.

Rheumatic and musculoskeletal diseases often affect individuals of childbearing age. The incidence and prevalence of rheumatic and musculoskeletal diseases is rising. More pregnancies in patients with rheumatic and musculoskeletal diseases are anticipated and some rheumatic and musculoskeletal diseases are associated with pregnancy complications (eg, miscarriages, fetal deaths, preterm births, and hypertensive disorders in pregnancy). Despite the need to understand the use of drugs to treat rheumatic and musculoskeletal diseases in pregnancy, clinical trials in pregnancy are rare, therapeutics in pregnancy are understudied, and pregnant individuals are routinely excluded as premarketing trial participants. Data on the effectiveness and safety of disease-modifying antirheumatic drugs are most often based on post-marketing observational data. Observational studies assessing the bidirectional relationship between rheumatic and musculoskeletal diseases and pregnancy, as well as interventional studies of treatments during pregnancy, are scarce. Historical reluctance to perform studies in what was deemed an at-risk group persists in pharmaceutical companies, regulatory bodies, and ethics boards. Additionally, patients must be engaged partners, which requires trust that the research respects the needs and interests of the patient and complies with the rules intended to protect the pregnant person and the fetus from harm. In this Series paper, we share challenges we have encountered in conducting prospective cohort studies and interventional trials of postmarketing approved medications, assessing pregnancy specific outcomes in pregnant women with rheumatic and musculoskeletal diseases in the EU, the UK, and the USA. We discuss the changing landscape around trials in pregnancy and present possible solutions to our challenges.

Relaxin as a treatment for musculoskeletal fibrosis: What we know and future directions.

Fibrotic changes in musculoskeletal diseases arise from the abnormal buildup of fibrotic tissue around the joints, leading to limited mobility, compromised joint function, and diminished quality of life. Relaxin (RLX) attenuates fibrosis by accelerating collagen degradation and inhibiting excessive extracellular matrix (ECM) production. Further, RLX disrupts myofibroblast activation by modulating the TGF-ß/Smads signaling pathways, which reduces connective tissue fibrosis. However, the mechanisms and effects of RLX in musculoskeletal pathologies are emerging as increasing research focuses on relaxin's impact on skin, ligaments, tendons, cartilage, joint capsules, connective tissues, and muscles. This review delineates the actions of relaxin within the musculoskeletal system and the challenges to its clinical application. Relaxin shows significant potential in both in vivo and in vitro studies for broadly managing musculoskeletal fibrosis; however, challenges such as short biological half-life and sex-specific responses may pose hurdles for clinical use.

Prognostic Factors and Treatment Effect Modifiers for Physical Health, Opioid Prescription, and Health Care Utilization in Patients With Musculoskeletal Disorders in Primary Care: Exploratory Secondary Analysis of the STEMS Randomized Trial of Direct Access to Physical Therapist-Led Care.

OBJECTIVE: The aims of the study were to identify prognostic factors associated with health care outcomes in patients with musculoskeletal (MSK) conditions in primary care and to determine whether characteristics associated with choice of care modify treatment effects of a direct-access physical therapist-led pathway in addition to general practitioner (GP)-led care compared to GP-led care alone. METHODS: A secondary analysis of a 2-parallel-arm, cluster randomized controlled trial involving general practices in the United Kingdom was conducted. Practices were randomized to continue offering GP-led care or to also offer a direct-access physical therapist-led pathway. Data from adults with MSK conditions who completed the 6-month follow-up questionnaire were analyzed. Outcomes included physical health, opioid prescription, and self-reported health care utilization over 6 months. Treatment effect modifiers were selected a priori from associations in observational studies. Multivariable regression models identified potential prognostic factors, and interaction analysis tested for potential treatment effect modifiers. RESULTS: Analysis of 767 participants indicated that baseline pain self-efficacy, pain severity, and having low back pain statistically predicted outcomes at 6 months. Higher pain self-efficacy scores at baseline were associated with improved physical health scores, reduced opioid prescription, and less health care utilization. Higher bodily pain at baseline and having low back pain were associated with worse physical health scores and increased opioid prescription. Main interaction analyses did not reveal that patients' age, level of education, duration of symptoms, or MSK presentation influenced response to treatment, but visual trends suggested those in the older age group proceeded to fewer opioid prescriptions and utilized less health care when offered direct access to physical therapy. CONCLUSIONS: Patients with MSK conditions with lower levels of pain self-efficacy, higher pain severity, and presenting with low back pain have less favorable clinical and health care outcomes in primary care. Prespecified characteristics did not modify the treatment effect of the offer of a direct-access physical therapist-led pathway compared to GP-led care. IMPACT: Patients with MSK conditions receiving primary care in the form of direct-access physical therapist-led or GP-led care who have lower levels of self-efficacy, higher pain severity, and low back pain are likely to have a less favorable prognosis. Age and duration of symptoms should be explored as potential patient characteristics that modify the treatment response to a direct-access physical therapist-led model of care.

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.

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.

Effects of serial radon spa therapy on pain and peripheral immune status in patients suffering from musculoskeletal disorders- results from a prospective, randomized, placebo-controlled trial.

In this randomized, placebo-controlled cross-over trial we aimed to investigate if radon spa therapy exerts more pain relief than exposure to warm water alone. In addition, immunological parameters were assessed in both treatment groups. In the RAD-ON02 trial, 116 patients suffering from musculoskeletal disorders (MSDs) received either serial radon spa or solely warm water baths. Pain intensity was assessed by determination of different pain parameters on a visual analogue scale and by pressure point dolorimetry at baseline and at weeks 4, 12 and 24. The longitudinal immune status of the patients was analyzed by a flow cytometry-based assay from peripheral blood at the time points of pain assessments. There were no side effects attributable to radon exposure observed. However, radon spa was superior to warm water applications at week 4 in terms of pain reduction. Pain and morning stiffness at the time of assessment were significantly reduced after radon spa (p<0.001, p<0.01) but not after warm water baths. The dolorimetry resulted in a significantly higher exerted pressure strength in patients after radon spa (p<0.001), but not after warm water applications. During the long-term follow-up, both treatment modalities reduced pain to a similar degree and pain modulation was not distorted by the participants' intake of analgesics. No significant changes in the immune status attributable specifically to radon were found, even though the increase in regulatory T cell counts occurs earlier after radon baths than after sole warm water baths and a higher level of significance is reached after radon spa at week 24. Serial radon spa has additive pain-relieving effects. The immunological parameters assessed in our study appear not to be directly linked to the pain reduction caused by radon exposure, at least in MSD patients with predominantly degenerative diseases. Clinical trial registration: https://www.clinicaltrialsregister.eu/ctr-search/search?query=rad-on02, identifier 2016-002085-31; https://drks.de/search/de/trial, identifier DRKS00016019.

NSAID use in orthopedic surgery: A review of current evidence and clinical practice guidelines.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a valuable class of medications for orthopedic surgeons and often play a pivotal role in pain control. However, there are many common stipulations resulting in avoidance of its use in the treatment of musculoskeletal disease. This review summarizes the mechanism of action of NSAIDs as well as provides an overview of commonly used NSAIDs and the differences between them. It provides a concise summary on the osseous effects of NSAIDs with regard to bone healing and heterotopic ossification. Most of all, it serves as a guide or reference for orthopedic providers when counseling patients on the risks and benefits of NSAID use, as it addresses the common stipulations encountered: "It irritates my stomach," "I have a history of bariatric surgery," "I'm already on a blood thinner," "I've had a heart attack," and "I've got kidney problems" and synthesizes both current research and society recommendations regarding safe use and avoidance of NSAIDs.

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.

United Kingdom physiotherapists injection therapy practice for musculoskeletal complaints: A cross-sectional survey.

BACKGROUND: Physiotherapists in the United Kingdom (UK), who have received additional training can adopt injection therapy for the treatment of musculoskeletal (MSK) disorders. OBJECTIVES: The objective of this practice survey was to explore (i) the frequency of use of injection therapy by UK physiotherapists for MSK disorders; and (ii) the clinical reasoning for selection of injectate, dose and pre/post injection practice. DESIGN: Cross-sectional online survey. METHODS: The online survey was disseminated via social media and professional networks over a 3-month period. Responses to closed multiple choice survey questions were analysed with descriptive data, with reporting of confidence intervals at 95%. Open questions were analysed using content analysis. RESULTS: The survey received 320 responses. The majority (86.6%, n = 277) used landmark guided approaches. The highest frequency of injections administered were for trigger digits, sub acromial pain and the knee joint. Corticosteroid drugs were widely used (99.7%, n = 319, CI 95% 98 to 100) with Triamcinolone (Kenalog) being the most frequently utilised for both joints (58.8%, n = 160, 53 to 65) and soft tissues (46.3%, n = 126, 40 to 52). Drug choice was largely based on availability in clinic (47.1%, n = 128, 41 to 53). Drug doses for common injection sites varied among the respondents with variation also evident in pre and post-injection practice. CONCLUSION: Marked variation across some elements of injection therapy practice was evident. Notable differences in corticosteroid preparation used, the doses of drug injected, and the use of local anaesthetic were reported by respondents. Injecting physiotherapists should endeavour to ensure practice is aligned to best available evidence.

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.

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.

Opioid Prescribing for Chronic Musculoskeletal Conditions: Trends over Time and Implementation of Safe Opioid-Prescribing Practices.

OBJECTIVES: This study aimed (1) to determine the impact of a clinical decision support (CDS) tool on rate of opioid prescribing and opioid dose for patients with chronic musculoskeletal conditions and (2) to identify prescriber and facility characteristics associated with adherence to the Centers for Disease Control and Prevention guideline for prescribing opioids for chronic pain in this population.We conducted an interrupted time series analysis to assess trends in percentage of patients from 2016 to 2020, receiving an opioid and the average opioid dose, as well as the change associated with implementation of the CDS toolkit. We conducted a retrospective cohort study to assess the association between prescriber and facility characteristics and safe opioid-prescribing practices. METHODS: We assessed the impact of the CDS intervention on percent of patients receiving an opioid and average opioid dose (morphine milligram equivalents). We operationalized safe opioid prescribing as a composite score of several behaviors (i.e., prescribing naloxone, initiating a pain agreement, prescribing <90 MME, avoiding extended-release prescriptions for opioid-naïve patients, and avoiding coprescribing opioids and benzodiazepines) and used a hierarchical linear regression model to assess associations between prescriber and facility characteristics and safe opioid prescribing. RESULTS: This CDS intervention had a modest but statistically significant 1.6% reduction on the percent of patients (n = 1,290,746) receiving an opioid (mean: 15% preintervention; 10% postintervention). The average dose of opioid prescriptions did not significantly change. Advanced practice providers and prescribers with higher percentages of patients aged 18 to 64 exhibited safer opioid prescribing, while prescribers with higher percentages of white patients and larger numbers of patients on opioids exhibited less safe opioid prescribing. CONCLUSION: A CDS intervention was associated with a small improvement in percent of patients receiving an opioid, but not on average dose. Clinicians are not prescribing opioids for chronic musculoskeletal conditions frequently, when they do, they are generally adhering to guidelines.

Curcumin nanoparticles and the therapeutic potential of curcumin for musculoskeletal disorders.

Musculoskeletal disorders (MSD) are a collection of degenerative conditions impacting the body's bones, joints, muscles, tendons, ligaments, and nerves. MSDs affect approximately 1.71 billion individuals worldwide and are a significant cause of disability. Curcumin is a polyphenolic compound with anti-inflammatory, antioxidant, and antitumor properties. In this review, we will discuss the research progress of structural analogs, derivatives, and nanomaterials that can improve the bioavailability of this natural drug. Curcumin may potentially retard the progression of osteoporosis, osteoarthritis, and rheumatoid arthritis. These effects may be related to curcumin's targeting of multiple signalling pathways.

Combined extract (Curcuma longa-Glycyrrhiza glabra) alleviates the inflammations of Achilles tendinopathy in Wistar rats.

OBJECTIVE: Achilles tendinopathy is a frequent pathological condition in adults with overused ankles, causing microtrauma, inducing tenocyte apoptosis and inflammatory response. Common treatment involves oral prescription or injection of anti-inflammatory agents, surgery, or shock-wave therapy. However, prolonged administration is not advisable due to adverse effects. Therefore, a novel and safe regimen is needed. Curcuma longa and Glycyrrhiza glabra extracts are known for their anti-inflammatory effects owing to their active compounds (curcumin and glycyrrhizin, respectively). This study aimed to determine the effect of combined extracts of Curcuma longa and Glycyrrhiza glabra on tendon healing in an animal model of Achilles tendinopathy (Wistar rats). MATERIALS AND METHODS: This study took place from February to May 2022 and compared the regimens administered to 32 animal models of Wistar rats with 4 healthy rats as a control group to determine the most effective therapeutic regimen: immobilization, immobilization with ibuprofen, or immobilization with the combined extract. The outcomes were measured to find which intervention provided the lowest inflammatory markers [High Mobility Group Box-1 (HMGB-1), Tumor Necrosis Factor-α (TNF-α), Chemokin motif ligand 12 (CXCL-12)], and improved tissue morphology represented by the BONAR score, decreased cross-sectional area (CSA), and increased Macrophage 2 (M2) differentiation. RESULTS: After Achilles tendinopathy was induced, total immobilization (I1) was proven to be the most effective with the lowest CSA, whereas immobilization+175 mg/kg Curcuma longa+110 mg/kg Glycyrrhiza glabra extract (I5) was the most effective with the lowest HMGB-1 levels and the lowest CXCL-12 levels. Immobilization+131 mg/kg Curcuma longa+82.5 mg/kg Glycyrrhiza glabra extract (I6) was the most effective with the lowest Bonar score, while immobilization+87.5 mg/kg Curcuma longa+55 mg/kg Glycyrrhiza glabra extract (I7) was proven to be the most effective with the highest M2 coverage area and the lowest TNF-α levels. CONCLUSIONS: We found that combined extract therapy was the most effective intervention for treating Achilles tendinopathy due to its ability to provide the lowest inflammatory markers.

Trends in consultations and prescribing for rheumatic and musculoskeletal diseases: an electronic primary care records study.

BACKGROUND: Rheumatic and musculoskeletal diseases (RMDs) are common and generally managed in primary care through supported self-care, physiotherapy, analgesia, and specialist referral where indicated. The COVID-19 pandemic led to abrupt changes in primary care delivery, including moves to remote consulting, pauses on group-based self-care, and restricted referrals. AIM: To describe how patterns of UK primary healthcare consultations and analgesic prescribing relating to RMDs changed during the COVID-19 pandemic. DESIGN AND SETTING: Observational study using routinely collected national primary care electronic health record data from the Clinical Practice Research Datalink between 1 April 2017 and 1 October 2021. METHOD: RMD and analgesic SNOMED-CT codes were derived through consensus and published work. Prevalent and incident RMD-related consultations were determined, and RMD consultations matched to prevalent and incident analgesia prescriptions. Joinpoint regression was used to describe trends over time. RESULTS: Prevalent and incident RMD consultations steadily increased until March 2020 when a substantial drop occurred as pandemic- related restrictions were introduced; levels had not recovered to pre-pandemic highs by October 2021. While incident and prevalent analgesic prescribing also reduced around March 2020, the proportion of patients with an RMD consultation prescribed any analgesic increased from 27.72% in February 2020 to 38.15% in April 2020, with increases across all analgesic groups. A higher proportion of strong opioid prescriptions was seen in the most deprived areas. CONCLUSION: Pandemic-associated restrictions led to fewer primary care consultations and relative increases in analgesic prescribing, including strong opioids, for RMDs in the UK. Policymakers must consider the impact of these changes in future healthcare resource planning.

Towards a consensus for nurse education of methotrexate for people with rheumatic and musculoskeletal diseases: A scoping review.

INTRODUCTION: Patient education (PE) is a key role of nurses, which includes providing information, training, and support about methotrexate (MTX), an anchor drug in rheumatology. However, there is a wide variation in the access to rheumatology nurse consultations in Europe, and there is a lack of consensus regarding the delivery, context and timing of PE in these cases. This study aimed to provide a comprehensive overview of the existing research on nurse education of MTX for children/youth and adults with Rheumatic and Musculoskeletal Diseases (RMDs). METHODS: This scoping review was conducted in accordance with Arksey and O'Malley's framework. A search on PubMed (MEDLINE), Scopus and Cochrane Database, and CINAHL, from inception until March 2022 was conducted. Articles on PE with a focus on MTX exclusively were included. Published and unpublished studies, from any world region, conducted with a qualitative, quantitative, or mixed-methods design and focused on defined research questions, were eligible for inclusion. Broad inclusion criteria were used if a research paper on PE focused on MTX for people with RMDs (PE or patient engagement, self-management, medication knowledge, or health literacy in patients). The reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses - Extension for Scoping Reviews (PRISMA-ScR) checklist. Two independent reviewers performed standardized data extraction and synthesis. RESULTS: From 292 references identified, the total number of studies which met the inclusion criteria was relatively small (n = 14). The results identified that knowledge of MTX improves when education by nurses is provided. CONCLUSION: This scoping review showed that there is no universal worldwide strategy for MTX education of children/youths and adults with RMDs. However, PE regarding MTX can be delivered in different forms, resulting in better satisfaction and adherence. More randomized controlled trials with powered samples are required.