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.

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.

Improvement of Pain Symptoms in Musculoskeletal Diseases After Multimodal Spa Therapy in the Austrian Gastein Valley-A Study Based on Longitudinal Registry Data.

Objective: The study aim was to investigate the course of pain in rest and motion in seven different rheumatic diseases (RMD), prior and after multimodal spa therapy including low-dose radon treatment and at 3-, 6-; and 9-month follow up. Methods: Complete data from the radon indication registry including information on 561 subjects with RMD were analysed to explore the association of timepoint of measurement with pain in rest and motion. For this purpose, linear regression models adjusted for RMD-type, age, sex and body mass index (BMI) were applied. Results: The mean age of the sample was 55 years, the average body mass index was 26.8, and 275 subjects were women. Pain scores were significantly improved at all-time points compared to baseline. Pain courses were different for each RMD with the largest improvement seen in fibromyalgia. Conclusion: Timing spa facility visits according to RMD-specific pain courses may result in sustained pain reduction.

Letrozole-induced inflammatory arthritis and tendinopathy in pediatric rheumatology setting.

Musculoskeletal symptoms associated with the use of aromatase inhibitors are a well-known side effect of these drugs and are more prevalent in postmenopausal women. Aromatase inhibitor-associated symptoms are not overt inflammatory processes so are described as arthralgia syndrome. In contrast, aromatase inhibitor-associated inflammatory conditions such as myopathies, vasculitis, and rheumatoid arthritis were also reported. To our knowledge, inflammatory arthritis or tendinopathy associated with aromatase inhibitors were not reported in children despite their increased off-label use in the pediatric setting. Herein, we report a girl with inflammatory arthritis and tendinopathy associated with letrozole treatment.

Pilot study of tocilizumab monotherapy for active chronic periaortitis.

OBJECTIVES: To investigate the effectiveness and safety of TCZ (tocilizumab) monotherapy for chronic periaortitis (CP) patients at acute active stage. METHODS: Twelve patients with definite or possible diagnosis of CP were enrolled and received intravenous infusions of TCZ (8 mg/kg) every 4 weeks for at least 3 months. Clinical features, laboratory and imaging findings were recorded at baseline and during the follow-up. The primary endpoint was the rate of partial and complete remission after 3 months TCZ monotherapy and the secondary endpoint was the frequency of treatment related adverse events. RESULTS: Three patients (27.3%) achieved partial remission and seven patients (63.6%) obtained complete remission after 3 months TCZ treatment. The total remission rate achieved 90.9%. All patients reported improvement in clinical symptoms. Inflammatory markers such as erythrocyte sedimentation rate and C reactive protein decreased to normal levels after TCZ treatment. Nine patients (81.8%) showed remarkable shrinkage of perivascular mass greater than or equal to 50% on CT. CONCLUSION: Our study showed that TCZ monotherapy contributed to remarkable clinical and laboratory improvement in CP patients and could be an alternative treatment option for CP.

Enfermedad musculoesquelética en población trabajadora: perfil de los afectados y manejo farmacológico / Musculoesqueletic diseases in working population: subjects' profile and pharmacological management

El presente estudio describe las enfermedades musculoesqueléticas (EME) de una cohorte de trabajadores de tipo manual, así como el uso de los fármacos indicados para el control del dolor. Estudio observacional retrospectivo llevado a cabo en el ámbito del Aragon Workers' Health Study (AWHS). Se ha analizado la prevalencia de las diferentes EME, la tasa de utilización de fármacos empleados en el tratamiento del dolor y el número de dosis diarias definidas (DDD) consumidas. El 15,4% de los trabajadores estudiados fueron diagnosticados de, al menos, una EME. De ellos, el 54,1% tenía sobrepeso y el 74,0% eran mayores de 55 años. La tasa de utilización de los antiinflamatorios no esteroideos (AINE) fue del 69,5%, y de los analgésicos no opiáceos, del 29,9%. Los datos presentados ponen de manifiesto la utilización elevada y, en algunos casos, continuada que existe de tratamientos analgésicos y antiinflamatorios. (AU)

The present study describes the musculoskeletal diseases (MSD) of a cohort of manual workers, as well as the use of drugs indicated for pain control. Retrospective observational study carried out within the framework of the Aragon Workers' Health Study (AWHS). The prevalence of the different EMEs, the rate of use of drugs used in the treatment of pain and the number of defined daily doses (DDD) consumed have been analysed. 15.4% of the workers studied were diagnosed with at least one EME. Of them, 54.1% were overweight and 74.0% were older than 55 years. The utilization rate of non-steroidal anti-inflammatory drugs (NSAIDs) was 69.5%, and of non-opioid analgesics, 29.9%. The data presented show the high use and, in some cases, the continuous use of analgesic and anti-inflammatory treatments. (AU)

2022 American College of Rheumatology Guideline for Vaccinations in Patients With Rheumatic and Musculoskeletal Diseases.

OBJECTIVE: To provide evidence-based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs). METHODS: This guideline follows American College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review for the PICO questions, graded the quality of evidence, and produced an evidence report. An expert Voting Panel reviewed the evidence and formulated recommendations. The panel included adult and pediatric rheumatology providers, infectious diseases specialists, and patient representatives. Consensus required ≥70% agreement on both the direction and strength of each recommendation. RESULTS: This guideline includes expanded indications for some vaccines in patients with RMDs, as well as guidance on whether to hold immunosuppressive medications or delay vaccination to maximize vaccine immunogenicity and efficacy. Safe approaches to the use of live attenuated vaccines in patients taking immunosuppressive medications are also addressed. Most recommendations are conditional and had low quality of supporting evidence. CONCLUSION: Application of these recommendations should consider patients' individual risk for vaccine-preventable illness and for disease flares, particularly if immunosuppressive medications are held for vaccination. Shared decision-making with patients is encouraged in clinical settings.

2022 American College of Rheumatology Guideline for Vaccinations in Patients With Rheumatic and Musculoskeletal Diseases.

OBJECTIVE: To provide evidence-based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs). METHODS: This guideline follows American College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review for the PICO questions, graded the quality of evidence, and produced an evidence report. An expert Voting Panel reviewed the evidence and formulated recommendations. The panel included adult and pediatric rheumatology providers, infectious diseases specialists, and patient representatives. Consensus required ≥70% agreement on both the direction and strength of each recommendation. RESULTS: This guideline includes expanded indications for some vaccines in patients with RMDs, as well as guidance on whether to hold immunosuppressive medications or delay vaccination to maximize vaccine immunogenicity and efficacy. Safe approaches to the use of live attenuated vaccines in patients taking immunosuppressive medications are also addressed. Most recommendations are conditional and had low quality of supporting evidence. CONCLUSION: Application of these recommendations should consider patients' individual risk for vaccine-preventable illness and for disease flares, particularly if immunosuppressive medications are held for vaccination. Shared decision-making with patients is encouraged in clinical settings.

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.