Subjects -> MEDICAL SCIENCES (Total: 8810 journals)
    - ANAESTHESIOLOGY (121 journals)
    - CARDIOVASCULAR DISEASES (350 journals)
    - DENTISTRY (292 journals)
    - ENDOCRINOLOGY (152 journals)
    - FORENSIC SCIENCES (44 journals)
    - HEMATOLOGY (159 journals)
    - HYPNOSIS (4 journals)
    - INTERNAL MEDICINE (180 journals)
    - MEDICAL GENETICS (58 journals)
    - MEDICAL SCIENCES (2448 journals)
    - NURSES AND NURSING (372 journals)
    - OBSTETRICS AND GYNECOLOGY (211 journals)
    - ONCOLOGY (395 journals)
    - OTORHINOLARYNGOLOGY (84 journals)
    - PATHOLOGY (100 journals)
    - PEDIATRICS (277 journals)
    - PSYCHIATRY AND NEUROLOGY (846 journals)
    - RESPIRATORY DISEASES (108 journals)
    - RHEUMATOLOGY (79 journals)
    - SPORTS MEDICINE (83 journals)
    - SURGERY (412 journals)

INTERNAL MEDICINE (180 journals)                     

Showing 1 - 180 of 180 Journals sorted alphabetically
Abdomen     Open Access  
ACP Hospitalist     Full-text available via subscription   (Followers: 9)
ACP Internist     Full-text available via subscription   (Followers: 10)
ACP Journal Club     Full-text available via subscription   (Followers: 11)
Acta Clinica Belgica     Hybrid Journal   (Followers: 1)
Acute and Critical Care     Open Access   (Followers: 11)
Acute Medicine     Full-text available via subscription   (Followers: 9)
Advances in Hepatology     Open Access   (Followers: 4)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6)
African Journal of Primary Health Care & Family Medicine     Open Access   (Followers: 6)
African Journal of Thoracic and Critical Care Medicine     Open Access  
American Family Physician     Full-text available via subscription   (Followers: 38)
American Journal of Hypertension     Hybrid Journal   (Followers: 31)
Anales de Medicina Interna     Open Access   (Followers: 1)
Anatomy & Physiology : Current Research     Open Access   (Followers: 9)
Angiology     Hybrid Journal   (Followers: 5)
Annals of Colorectal Research     Open Access   (Followers: 1)
Annals of Internal Medicine     Full-text available via subscription   (Followers: 392)
AORN Journal     Hybrid Journal   (Followers: 27)
Apollo Medicine     Open Access  
Archives of Drug Information     Hybrid Journal   (Followers: 5)
Archivos de Medicina Interna     Open Access   (Followers: 1)
Asia Oceania Journal of Nuclear Medicine & Biology     Open Access   (Followers: 4)
Asian Pacific Journal of Tropical Disease     Full-text available via subscription   (Followers: 3)
Australasian Physical & Engineering Sciences in Medicine     Hybrid Journal   (Followers: 1)
BMI Journal : Bariátrica & Metabólica Iberoamericana     Open Access   (Followers: 1)
BMJ Open Diabetes Research & Care     Open Access   (Followers: 35)
BMJ Quality & Safety     Hybrid Journal   (Followers: 69)
Bone & Joint Journal     Hybrid Journal   (Followers: 138)
Brain Communications     Open Access   (Followers: 4)
Brain Science Advances     Open Access  
Canadian Journal of General Internal Medicine     Open Access   (Followers: 2)
Cardiovascular Medicine in General Practice     Full-text available via subscription   (Followers: 7)
Case Reports in Internal Medicine     Open Access   (Followers: 1)
Cell Death & Disease     Open Access   (Followers: 3)
Cellular and Molecular Gastroenterology and Hepatology     Open Access   (Followers: 3)
Cephalalgia     Hybrid Journal   (Followers: 8)
Cephalalgia Reports     Open Access   (Followers: 4)
Chronic Diseases and Injuries in Canada     Free   (Followers: 1)
Clinical Ethics     Hybrid Journal   (Followers: 13)
Clinical Liver Disease     Open Access   (Followers: 5)
Clinical Nutrition     Hybrid Journal   (Followers: 98)
Clinical Thyroidology     Full-text available via subscription   (Followers: 1)
CNE Pflegemanagement     Hybrid Journal  
Communication Law and Policy     Hybrid Journal   (Followers: 5)
Current Diabetes Reports     Hybrid Journal   (Followers: 30)
Current Hepatology Reports     Hybrid Journal  
Current Research: Integrative Medicine     Open Access  
CVIR Endovascular     Open Access   (Followers: 1)
Der Internist     Hybrid Journal   (Followers: 12)
Diabetes     Full-text available via subscription   (Followers: 603)
Diabetes Care     Full-text available via subscription   (Followers: 578)
Diabetes Internacional     Open Access  
Diabetes Spectrum     Full-text available via subscription   (Followers: 17)
Diagnosis     Hybrid Journal   (Followers: 1)
Egyptian Journal of Bronchology     Open Access  
Egyptian Journal of Internal Medicine     Open Access   (Followers: 1)
Egyptian Journal of Neurosurgery     Open Access  
Egyptian Liver Journal     Open Access   (Followers: 2)
Egyptian Spine Journal     Open Access  
EMC - Aparato Locomotor     Hybrid Journal  
Endovascular Neuroradiology / Ендоваскулярна нейрорентгенохірургія     Open Access   (Followers: 1)
eNeuro     Open Access   (Followers: 3)
Ergonomics     Hybrid Journal   (Followers: 24)
European Journal of Inflammation     Open Access   (Followers: 2)
European Journal of Internal Medicine     Full-text available via subscription   (Followers: 10)
European Journal of Translational Myology     Open Access  
European Radiology Experimental     Open Access   (Followers: 2)
Head and Neck Tumors     Open Access   (Followers: 1)
Health Sociology Review     Hybrid Journal   (Followers: 14)
HemaSphere     Open Access   (Followers: 2)
Hepatology Communications     Open Access  
Hepatoma Research     Open Access   (Followers: 3)
Human Physiology     Hybrid Journal   (Followers: 5)
ImmunoHorizons     Open Access  
Immunological Medicine     Open Access  
Infectious Diseases: Research and Treatment     Open Access   (Followers: 5)
Inflammation and Regeneration     Open Access   (Followers: 2)
Inflammatory Intestinal Diseases     Open Access  
Innere Medizin up2date     Hybrid Journal   (Followers: 1)
Internal and Emergency Medicine     Hybrid Journal   (Followers: 5)
Internal Medicine Journal     Hybrid Journal   (Followers: 9)
International Journal of Abdominal Wall and Hernia Surgery     Open Access   (Followers: 1)
International Journal of Anatomy and Research     Open Access   (Followers: 2)
International Journal of Angiology     Hybrid Journal  
International Journal of Artificial Organs     Hybrid Journal   (Followers: 3)
International Journal of Hyperthermia     Open Access  
International Journal of Internal Medicine     Open Access   (Followers: 3)
International Journal of Noncommunicable Diseases     Open Access  
International Journal of Psychiatry in Clinical Practice     Hybrid Journal   (Followers: 6)
Iranian Journal of Neurosurgery     Open Access   (Followers: 1)
Italian Journal of Anatomy and Embryology     Open Access   (Followers: 1)
JAC-Antimicrobial Resistance     Open Access   (Followers: 4)
JAMA Internal Medicine     Full-text available via subscription   (Followers: 364)
JCSM Clinical Reports     Open Access   (Followers: 3)
JHEP Reports     Open Access  
JIMD Reports     Open Access  
JMV - Journal de Médecine Vasculaire     Hybrid Journal   (Followers: 1)
Joint Commission Journal on Quality and Patient Safety     Hybrid Journal   (Followers: 41)
JOP. Journal of the Pancreas     Open Access   (Followers: 2)
Journal of Basic & Clinical Physiology & Pharmacology     Hybrid Journal   (Followers: 1)
Journal of Bone Oncology     Open Access   (Followers: 1)
Journal of Cancer & Allied Specialties     Open Access  
Journal of Clinical and Experimental Hepatology     Full-text available via subscription   (Followers: 3)
Journal of Clinical Movement Disorders     Open Access   (Followers: 3)
Journal of Community Hospital Internal Medicine Perspectives     Open Access  
Journal of Cutaneous Immunology and Allergy     Open Access  
Journal of Developmental Origins of Health and Disease     Hybrid Journal   (Followers: 2)
Journal of Endoluminal Endourology     Open Access  
Journal of Gastroenterology and Hepatology Research     Open Access   (Followers: 4)
Journal of General Internal Medicine     Hybrid Journal   (Followers: 23)
Journal of Hypertension     Hybrid Journal   (Followers: 14)
Journal of Infectious Diseases     Hybrid Journal   (Followers: 48)
Journal of Interdisciplinary Medicine     Open Access  
Journal of Internal Medicine     Hybrid Journal   (Followers: 11)
Journal of Liver : Disease & Transplantation     Hybrid Journal   (Followers: 7)
Journal of Medical Internet Research     Open Access   (Followers: 24)
Journal of Movement Disorders     Open Access   (Followers: 2)
Journal of Pain and Symptom Management     Hybrid Journal   (Followers: 46)
Journal of Pancreatic Cancer     Open Access  
Journal of Renal and Hepatic Disorders     Open Access  
Journal of Solid Tumors     Open Access   (Followers: 1)
Journal of Sports Medicine and Allied Health Sciences : Official Journal of the Ohio Athletic Trainers Association     Open Access   (Followers: 1)
Journal of the American Board of Family Medicine     Open Access   (Followers: 11)
Journal of the European Mosquito Control Association     Open Access  
Journal of Translational Internal Medicine     Open Access  
Jurnal Vektor Penyakit     Open Access  
La Revue de Medecine Interne     Full-text available via subscription   (Followers: 3)
Lege artis - Das Magazin zur ärztlichen Weiterbildung     Hybrid Journal   (Followers: 1)
Liver Cancer International     Open Access  
Liver Research     Open Access  
Molecular Diagnosis & Therapy     Hybrid Journal   (Followers: 3)
Molecular Therapy - Oncolytics     Open Access  
Multiple Sclerosis and Demyelinating Disorders     Open Access   (Followers: 7)
MYOPAIN. A journal of myofascial pain and fibromyalgia     Hybrid Journal   (Followers: 18)
Neuro-Oncology Advances     Open Access   (Followers: 1)
Neurobiology of Pain     Open Access   (Followers: 2)
Neurointervention     Open Access   (Followers: 6)
Neuromuscular Diseases     Open Access  
Nigerian Journal of Gastroenterology and Hepatology     Full-text available via subscription  
OA Alcohol     Open Access   (Followers: 5)
Oncological Coloproctology     Open Access  
Open Journal of Internal Medicine     Open Access  
Pleura and Peritoneum     Open Access  
Pneumo News     Full-text available via subscription  
Polish Archives of Internal Medicine     Full-text available via subscription   (Followers: 2)
Preventing Chronic Disease     Free   (Followers: 2)
Progress in Transplantation     Hybrid Journal   (Followers: 1)
Prostate International     Open Access   (Followers: 2)
Psychiatry and Clinical Psychopharmacology     Open Access   (Followers: 1)
Pulmonary Therapy     Open Access   (Followers: 2)
Quality of Life Research     Hybrid Journal   (Followers: 20)
Research and Practice in Thrombosis and Haemostasis     Open Access  
Revista Chilena de Fonoaudiología     Open Access   (Followers: 1)
Revista de la Sociedad Peruana de Medicina Interna     Open Access   (Followers: 4)
Revista del Instituto de Medicina Tropical     Open Access  
Revista Hispanoamericana de Hernia     Open Access   (Followers: 1)
Revista Médica Internacional sobre el Síndrome de Down     Full-text available via subscription   (Followers: 1)
Revista Virtual de la Sociedad Paraguaya de Medicina Interna     Open Access   (Followers: 1)
Romanian Journal of Diabetes Nutrition and Metabolic Diseases     Open Access   (Followers: 1)
Romanian Journal of Internal Medicine     Open Access  
Russian Journal of Child Neurology     Open Access   (Followers: 1)
Scandinavian Journal of Primary Health Care     Open Access   (Followers: 8)
Schlaf     Hybrid Journal  
Schmerzmedizin     Hybrid Journal  
Scientific Journal of the Foot & Ankle     Open Access   (Followers: 1)
SciMedicine Journal     Open Access   (Followers: 3)
SEMERGEN - Medicina de Familia     Full-text available via subscription   (Followers: 1)
The Journal of Critical Care Medicine     Open Access   (Followers: 9)
Therapeutic Advances in Chronic Disease     Open Access   (Followers: 8)
Therapeutic Advances in Musculoskeletal Disease     Hybrid Journal   (Followers: 6)
Thieme Case Report     Hybrid Journal   (Followers: 1)
Tijdschrift voor Urologie     Hybrid Journal  
Tissue Barriers     Hybrid Journal   (Followers: 1)
Transactions of the Royal Society of Tropical Medicine and Hygiene     Hybrid Journal   (Followers: 3)
Transgender Health     Open Access   (Followers: 3)
Trends in Anaesthesia and Critical Care     Full-text available via subscription   (Followers: 23)
US Cardiology Review     Open Access  
Vascular and Endovascular Review     Open Access   (Followers: 1)
Ожирение и метаболизм     Open Access  


Similar Journals
Journal Cover
Therapeutic Advances in Musculoskeletal Disease
Journal Prestige (SJR): 1.118
Citation Impact (citeScore): 3
Number of Followers: 6  
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1759-720X - ISSN (Online) 1759-7218
Published by Sage Publications Homepage  [1151 journals]
  • Future projections of opioid use and cost in patients with chronic
           osteoarthritis pain in Spain
    • Authors: Javier Rejas-Gutierrez, Antoni Sicras-Mainar, Josep Darbà
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Background:Opioids are widely used in moderate-to-severe chronic pain which is non-responsive to standard analgesics. Prescriptions have increased in Europe in the last decade, although remain lower than in USA. This work projected the future utilization and costs of opioids in chronic osteoarthritis (OA) pain in the Spanish National Health System (NHS).Methods:An epidemiological model was populated with the opioid dispensing trends from 2010 to 2019 using Spanish Medicinal Agency rates of opioid utilization in subjects over 18 years of age and the real-world OPIOIDS study to estimate chronic-OA-pain patients receiving opioids. A best-fitted trend analysis model was applied estimating the likely number of DHD (defined daily dose/1000 inhabitants per day) to calculate projected opioid utilization and costs for the period 2020–2029.Results:In 2010, an estimated 5.67 DHD were dispensed for the equivalent of 217,076 chronic OA pain patients per day [1.99 DHD, 76,084 refractory to non-steroidal anti-inflammatory drugs (NSAIDs)]. From these trends and OA prevalence, the projected number of DHDs is expected to increase more than threefold to 17.98 DHDs by the year 2029 for the equivalent of 727,356 chronic OA pain patients per day (8.18 DHD, 330,720 refractory to NSAIDs); 41.8% on strong opioids. The estimated cost was €116.9m (€45.0m in NSAID-refractory OA) in 2010 rising by 222% to €376.1m (€199.7m refractory to NSAIDs) by 2029.Conclusion:Chronic-OA-pain-related opioid dispensing and costs to the NHS are set to increase more than threefold from 2010 to 2029 in Spain. Using opioids for OA pain is concerning given disease chronicity and other related costs not computed in these projections.Plain language summary• Opioids are widely used in chronic pain which is non-responsive to standard analgesics. Prescriptions have increased in Europe, although remain lower than in USA. Osteoarthritis (OA) is a degenerative joint disease usually accompanied by pain. Despite not recommended, opioids use in OA have been expanded because this health condition is increasing with ageing and, also, because physicians both primary and specialist boosted their use.• This study aimed to quantify the current burden of opioids used for chronic moderate-to-severe OA pain by estimating the number of defined daily doses per 1000 inhabitants per day (DHD) and associated costs, and to forecast the likely burden on the National Health System (NHS) in Spain for the years 2020–2029.• In 2010, an estimated 5.67 DHDs were dispensed for the equivalent of 217,076 chronic OA pain patients per day. From these trends, the projected number of DHDs is expected to increase more than threefold to 17.98 DHDs by the year 2029 for the equivalent of 727,356 chronic OA pain patients per day; 41.8% on strong opioids. The estimated cost was €116.9m in 2010 rising by 222% to €376.1m by 2029.• Chronic OA-pain-related opioid dispensing and costs to the NHS are set to increase substantially (threefold to more than fourfold) from 2010 to 2029 in Spain. Thus, using opioids for OA pain is concerning given disease chronicity, aging population and other related costs not computed in these projections. Our findings can inform payors and clinicians about ongoing discussions on appropriate analgesic management for longer-term OA pain, including resource requirements at a national level. Clinicians who prescribe opioids for OA pain should consider the potential implications of side effects such as sedation, cognitive deterioration, incremental need of caregivers, particularly in older people, and carefully consider the risk–benefit balance.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-04-29T09:28:31Z
      DOI: 10.1177/1759720X211010599
      Issue No: Vol. 13 (2021)
  • Low-dose IL-2 therapy limits the reduction in absolute numbers of
           circulating regulatory T cells in rheumatoid arthritis
    • Authors: Sheng-Xiao Zhang, Jia Wang, Cai-Hong Wang, Rui-Huan Jia, Ming Yan, Fang-Yuan Hu, Guang-Ying Liu, Xue-Yu Liu, Jing Luo, Chong Gao, Xiao-Feng Li
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Background:Circulating regulatory T cells (Tregs) are responsible for mediating immune tolerance and maintaining immunological homeostasis. Decreases in Tregs may be involved in the onset of rheumatoid arthritis (RA). Low-dose interleukin-2 (IL-2) has been considered for the treatment of inflammatory diseases mediated by T cells. This study focused on the status of circulating CD4+T subsets and the clinical feasibility of IL-2 therapies in patients with RA.Methods:The subjects included 888 patients with RA and 100 healthy controls (HCs); 233 RA patients received IL-2 treatment with 0.5 million international units (MIU)/day from days 1 through 5. The demographic features, disease activity, and levels of CD4+T cells measured by modified flow cytometry were collected in all RA patients before and after treatment.Results:RA patients had lower absolute Treg counts (but not Th17) compared with HCs, which was associated with disease activity; previously treated RA patients had the fewest circulating Tregs (p 
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-04-28T12:22:12Z
      DOI: 10.1177/1759720X211011370
      Issue No: Vol. 13 (2021)
  • Direct oral anticoagulants and the risk of osteoporotic fractures in
           patients with non-valvular atrial fibrillation
    • Authors: Liang-Tseng Kuo, Su-Ju Lin, Victor Chien-Chia Wu, Jung-Jung Chang, Pao-Hsien Chu, Yu-Sheng Lin
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Background:The incidence of osteoporotic fracture increases with age, particularly in elderly populations with atrial fibrillation (AF). However, direct oral anticoagulants (DOACs) have less effect on osteoporotic fracture than vitamin K antagonists, it is unclear whether the risk of osteoporotic fracture is affected by different types and doses of DOACs in AF patients.Methods:This nationwide population-based cohort study included AF patients prescribed DOACs between 2011 and 2016 taken from the Taiwan National Health Insurance database. Adjusted hazard ratios (aHRs) for the risk of osteoporotic, hip, and spine fractures between DOAC users were compared using the Fine and Gray subdistribution hazard model to adjust for possible confounders.Results:A total of 56,795 patients who were prescribed DOACs were included in the present study. Among them, 24,597 patients received dabigatran, 26,968 received rivaroxaban, and 5230 received apixaban. After 2 years’ follow up, there was no significant difference in the incidence of osteoporotic, spine, or hip fracture among those receiving dabigatran, rivaroxaban, or apixaban. Subgroup analysis showed that patients taking dabigatran had a higher incidence of osteoporotic and hip fracture than those taking rivaroxaban and apixaban in cases with concomitant peripheral artery disease (PAD) or a history of hip fracture (p for interaction: 0.004 and 0.030, respectively). However, dabigatran users had a lower incidence of osteoporotic fracture and spine fracture in those receiving standard-dose DOACs compared with rivaroxaban and apixaban; whereas, they had a higher incidence of hip fractures when administered at low dose.Conclusion:AF patients with different DOACs did not have different risks of osteoporotic fracture overall. However, additional concomitant morbidities, such as PAD or a history of hip fracture, and standard/low doses might be associated with different risks for different DOACs. These findings should be taken into consideration in the clinic when the DOAC is being chosen.Plain language summaryDifferent direct oral anticoagulants had different impact on osteoporotic fractureAnticoagulation therapy is an essential therapy in atrial fibrillation (AF) patients, but osteoporotic fracture is another important issue in these patients prescribed with anticoagulants. However, no study has been conducted to evaluate the impact of different DOACs on different types of osteoporotic fractures. In our findings, although different DOACs had no significantly different impact on osteoporotic fractures, dabigatran users had a slightly higher incidence of osteoporotic and hip fractures among different DOACs, particularly in those have simultaneously had peripheral artery disease, a history of hip fracture. In addition, when AF patients taking low-dose DOACs, dabigatran users also have higher incidence of hip fracture than those taking other DOACs.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-04-27T10:07:02Z
      DOI: 10.1177/1759720X211011374
      Issue No: Vol. 13 (2021)
  • Analysis of factors that drives arthrocentesis for suspected septic joint
    • Authors: Cameron A. Roth, Tony Da Lomba, Rahul Dadwani, James Dahm, Jason Strelzow
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Introduction:This study aims to develop a simple diagnostic criterion that could be used to justify arthrocentesis in adults with suspected septic arthritis. Our hypothesis is that no single factor will be predictive for a decision to aspirate a questionable septic joint.Methods:A prospective observational cohort study was performed at a Level 1 Trauma institution including all patients over the age of 18 years referred to Orthopaedics through the Emergency Department or inpatient orthopaedic consultations for a suspected septic joint. Patient information recorded was age, laboratory markers (white blood cell count, erythrocyte sedimentation rate, C-reactive protein, physical exam findings (fever, pain with range-of-motion), and presence of smoking, diabetes, end-stage renal disease (ESRD) on dialysis, and body mass index > 30. Continuous data was analyzed using logistic regression, and nominal data was analyzed using a two-tailed Fisher’s exact test.Results:A total of 128 patients met inclusion criteria for this study; 71 patients underwent arthrocentesis for suspected septic joint. On analysis of risk factors, the demographics, laboratory markers, physical exam and comorbidities were not significant between the two groups. On subset analysis of the septic joints, we found the only risk factor to be significantly predictive of whether a joint was septic was the presence of ESRD on dialysis (p = 0.042).Conclusion:Past data have looked solely at predictive risk factors for septic arthritis; however, this study aims to predict what drives physicians towards aspirating a joint even before it is determined to be septic. We found no single factor was predictive of joint aspiration. Only ESRD on dialysis is predictive of whether a joint with concern for septic arthritis would ultimately be septic in our institution. The decision to aspirate continues to be best determined by clinician judgment in light of experience and available clinical information.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-04-23T06:21:35Z
      DOI: 10.1177/1759720X211002582
      Issue No: Vol. 13 (2021)
  • Ultrasonography predicts the results of labial salivary gland biopsy in
           patients with suspected Sjögren’s syndrome: a matrix risk model
    • Authors: Ying-Qian Mo, Shao-Yun Hao, Qian-Hua Li, Jin-Jian Liang, Yi Luo, Yu-Qing Lan, Jiang-Long Zhong, Jun-Wei Wang, Xue-Pei Zhang, Wen-Ke Huang, Lie Dai
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Objective:Although a positive result of labial salivary gland biopsy (LSGB) is critical for the diagnosis of Sjögren’s syndrome, rheumatologists prefer assessing the non-invasive objective items and hope to learn the predicted probability of positive LSGB before referring patients with suspected Sjögren’s syndrome to receive biopsy. This study aimed to explore the predictive value of combined B-mode ultrasonography (US) and shear-wave elastography (SWE) examination on LSGB results.Methods:A derivation cohort and later a validation cohort of patients with suspected Sjögren’s syndrome were recruited. All participants received clinical assessments, B-mode US and SWE examination on bilateral parotid and submandibular glands before LSGB. Positive LSGB was defined by a focus score ⩾1 per 4 mm2 of glandular tissue.Results:In the derivation cohort of 91 participants, either the total US scores or the total SWE values of four glands significantly distinguished patients with positive LSGB from those with negative results (area under the curve (AUC) = 0.956, 0.825, both p 
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-04-23T06:19:57Z
      DOI: 10.1177/1759720X211010592
      Issue No: Vol. 13 (2021)
  • Patient-reported outcomes from a randomized, double-blind, placebo
           controlled, phase III study of baricitinib versus placebo in patients with
           moderately to severely active rheumatoid arthritis and an inadequate
           response to methotrexate therapy: results from the RA-BALANCE study
    • Authors: Yue Yang, Jianhua Xu, Jian Xu, Xingfu Li, Jiankang Hu, Xiangpei Li, Xiao Zhang, Dongyi He, Chunde Bao, Zhijun Li, Guochun Wang, Cristiano A. F. Zerbini, Alberto J. Spindler, Carol L. Kannowski, Hanjun Wu, Fei Ji, Lujing Zhan, Mengru Liu, Zhanguo Li
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Introduction:To assess the effect of baricitinib on patient-reported outcomes (PROs) in patients with moderately to severely active rheumatoid arthritis (RA) who had an inadequate response to methotrexate (MTX).Methods:This was a 52-week, randomized, double-blind, placebo controlled, phase III study in patients with RA who had an inadequate response to MTX. Patients (n = 290) receiving stable background MTX were randomly assigned (1:1) to receive placebo or baricitinib 4 mg once daily with a primary endpoint at week 12. PROs assessed included Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient’s Global Assessment of Disease Activity, patient’s assessment of pain, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), European Quality of Life-5 Dimensions-5 Level index scores and visual analogue scale, and measures collected in electronic patient daily diaries: duration of morning joint stiffness, Worst Tiredness, and Worst Joint Pain. Treatment comparisons were made with logistic regression and analysis of covariance models for categorical and continuous variables, respectively.Results:Statistically significant (p ⩽ 0.05) improvements in all PROs were observed in the baricitinib 4 mg group compared to placebo as early as week 1 to week 4; and were sustained to week 24. These improvements were maintained until week 52 for the baricitinib group. A significantly larger proportion of patients met or exceeded the minimum clinically important difference for HAQ-DI (⩾0.22) and FACIT-F (3.56) profiles in the baricitinib group.Conclusion:Baricitinib provided significant improvements in PROs compared to placebo to 52 weeks of treatment in patients with RA who had an inadequate response to identifier:; NCT02265705; RA-BALANCE. Registered 13 October 2014
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-04-21T06:54:26Z
      DOI: 10.1177/1759720X211006964
      Issue No: Vol. 13 (2021)
  • Comparison of three treatment protocols with intra-articular low or
           intermediate molecular weight hyaluronic acid in early symptomatic knee
    • Authors: Felice Galluccio, Daniela D’Angela, Barbara Polistena, Francesco Porta, Tatiana Barskova, Lorenzo Tofani, Federico Spandonaro, Marco Matucci-Cerinic
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Introduction:Viscosupplementation with hyaluronic acid (HA) is indicated for non-responders to non-pharmacological therapy, to analgesics or when non-steroidal anti-inflammatory drugs (NSAIDs) are contraindicated. The aim of this study is to compare the efficacy, safety and costs of three different HA treatments (Sinovial® Forte, sinovial one and hyalgan).Patients and methods:Ninety patients with grade I/II Kellgren–Lawrence knee osteoarthritis were included in three groups, the first was treated with hyalgan (weekly for 5 weeks), the second with Sinovial® Forte (weekly for 3 weeks) and the third group with a single injection of sinovial one.Results:All three treatments were effective, with an average reduction in the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) score of 18.9 points for hyalgan, 18.04 points for Sinovial® Forte and 17.92 points for sinovial one. The comparison of the three groups did not show any statistical difference in terms of efficacy. National health system (NHS) and social costs are, respectively, €419.12 and €853.43 for hyalgan, €338.64 and €599.22 for Sinovial® Forte, €221.56 and €308.42 for sinovial one.Conclusion:All three treatments were equally effective with no statistically significant differences; thus, the treatment with sinovial one may be considered as clinically effective as the other two regimens, but with a very efficient cost profile in early symptomatic knee osteoarthritis.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-04-21T06:46:36Z
      DOI: 10.1177/1759720X21994024
      Issue No: Vol. 13 (2021)
  • Interactions of the microbiome with pharmacological and
           non-pharmacological approaches for the management of ageing-related
           musculoskeletal diseases
    • Authors: Maria Papageorgiou, Emmanuel Biver
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Despite major progress in the understanding of the pathophysiology and therapeutic options for common ageing-related musculoskeletal conditions (i.e. osteoporosis and associated fractures, sarcopenia and osteoarthritis), there is still a considerable proportion of patients who respond sub optimally to available treatments or experience adverse effects. Emerging microbiome research suggests that perturbations in microbial composition, functional and metabolic capacity (i.e. dysbiosis) are associated with intestinal and extra-intestinal disorders including musculoskeletal diseases. Besides its contributions to disease pathogenesis, the role of the microbiome is further extended to shaping individuals’ responses to disease therapeutics (i.e. pharmacomicrobiomics). In this review, we focus on the reciprocal interactions between the microbiome and therapeutics for osteoporosis, sarcopenia and osteoarthritis. Specifically, we identify the effects of therapeutics on microbiome’s configurations, functions and metabolic output, intestinal integrity and immune function, but also the effects of the microbiome on the metabolism of these therapeutics, which in turn, may influence their bioavailability, efficacy and side-effect profile contributing to variable treatment responses in clinical practice. We further discuss emerging strategies for microbiota manipulation as preventive or therapeutic (alone or complementary to available treatments) approaches for improving outcomes of musculoskeletal health and disease.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-04-21T06:44:23Z
      DOI: 10.1177/1759720X211009018
      Issue No: Vol. 13 (2021)
  • Osteopathic medicine for fibromyalgia: a sham-controlled randomized
           clinical trial
    • Authors: Joël Coste, Terkia Medkour, Jean-Yves Maigne, Marc Pérez, Françoise Laroche, Serge Perrot
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Background:Patients with fibromyalgia (FM) frequently resort to osteopathic or chiropractic treatment, despite very weak supporting evidence. We aimed to assess the efficacy of osteopathic manipulation in FM in a properly controlled and powered randomized clinical trial.Methods:Patients were randomized to osteopathic or sham treatment. Treatment was administered by experienced physical medicine physicians, and consisted of six sessions per patient, over 6 weeks. Treatment credibility and expectancy were repeatedly evaluated. Patients completed standardized questionnaires at baseline, during treatment, and at 6, 12, 24, and 52 weeks after randomization. The primary outcome was pain intensity (100-mm visual analog scale) during the treatment period. Secondary outcomes included fatigue, functioning, and health-related quality of life. We performed primarily intention-to-treat analyses adjusted for credibility, using multiple imputation for missing data.Results:In total, 101 patients (94% women) were included. Osteopathic treatment did not significantly decrease pain relative to sham treatment (mean difference during treatment: −2.2 mm; 95% confidence interval, −9.1 to 4.6 mm). No significant differences were observed for secondary outcomes. No serious adverse events were observed, despite a likely rebound in pain and altered functioning at week 12 in patients treated by osteopathy. Patient expectancy was predictive of pain during treatment, with a decrease of 12.9 mm (4.4–21.5 mm) per 10 points on the 0–30 scale. Treatment credibility and expectancy were also predictive of several secondary outcomes.Conclusion:Osteopathy conferred no benefit over sham treatment for pain, fatigue, functioning, and quality of life in patients with FM. These findings do not support the use of osteopathy to treat these patients. More attention should be paid to the expectancy of patients in FM management.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-04-17T05:37:20Z
      DOI: 10.1177/1759720X211009017
      Issue No: Vol. 13 (2021)
  • The sonographic identification of cortical bone interruptions in
           rheumatoid arthritis: a morphological approach
    • Authors: Edoardo Cipolletta, Gianluca Smerilli, Andrea Di Matteo, Jacopo Di Battista, Marco Di Carlo, Walter Grassi, Emilio Filippucci
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Bone erosions are the hallmark of structural damage in rheumatoid arthritis (RA). Among imaging techniques, ultrasonography (US) has emerged as an accurate, reliable, repeatable, low-cost and non-invasive imaging modality to detect erosive changes in RA. However, small interruptions of the cortical bone detectable by last generation US equipment do not necessarily represent bone erosions. According to the available data, in addition to cortical bone interruption itself, only a few morphological US findings have been proposed to define RA bone erosions. However, other additional features may be considered to facilitate the interpretation of US cortical bone interruptions in RA. These could be summarised using the following four domains: size, site, shape and scenery. This hypothesis article provides a critical literature review of US features characteristic of RA bone erosions and pictorial evidence supporting the potential role of a morphological analysis in the US identification of bone erosions in RA patients.Plain language summaryThe ultrasonographic morphology of cortical interruptions is helpful for the identification of bone erosions in rheumatoid arthritis: the “four Ss” approachBone erosions are characteristic features of rheumatoid arthritis. They are associated with a more aggressive disease and with irreversible physical disability. In recent years, ultrasonography has emerged as an accurate and reliable technique for the detection of bone erosions, that appear as interruptions of the cortical bone with variable size. However, cortical bone interruptions do not necessarily represent bone erosions. Since bone erosions represent the earliest evidence of the destructive behaviour of RA, their identification is crucial.Besides the cortical interruption itself, only a few morphological ultrasonographic features were proposed to characterise bone erosions in rheumatoid arthritis.We believe that a morphological approach, including size, site, shape and scenery, may be considered to facilitate the interpretation of ultrasonographic cortical bone interruptions in rheumatoid arthritis.In this hypothesis article we carried out a critical review of the scientific literature and provided extensive pictorial evidence of the ultrasonographic spectrum of cortical interruptions supporting the potential role of considering the “four Ss” for the ultrasonographic identification of bone erosions in rheumatoid arthritis.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-04-17T05:34:20Z
      DOI: 10.1177/1759720X211004326
      Issue No: Vol. 13 (2021)
  • Promising targets for therapy of osteoarthritis: a review on the Wnt and
           TGF-β signalling pathways
    • Authors: Chahrazad Cherifi, Silvia Monteagudo, Rik J. Lories
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Osteoarthritis (OA) is the most common chronic joint disorder worldwide, with a high personal burden for the patients and an important socio-economic impact. Current therapies are largely limited to pain management and rehabilitation and exercise strategies. For advanced cases, joint replacement surgery may be the only option. Hence, there is an enormous need for the development of effective and safe disease-modifying anti-OA drugs. A strong focus in OA research has been on the identification and role of molecular signalling pathways that contribute to the balance between anabolism and catabolism in the articular cartilage. In this context, most insights have been gained in understanding the roles of the transforming growth factor-beta (TGF-β) and the Wingless-type (Wnt) signalling cascades. The emerging picture demonstrates a high degree of complexity with context-dependent events. TGF-β appears to protect cartilage under healthy conditions, but shifts in its receptor use and subsequent downstream signalling may be deleterious in aged individuals or in damaged cartilage. Likewise, low levels of Wnt activity appear important to sustain chondrocyte viability but excessive activation is associated with progressive joint damage. Emerging clinical data suggest some potential for the use of sprifermin, a recombinant forms of fibroblast growth factor 18, a distant TGF-β superfamily member, and for lorecivivint, a Wnt pathway modulator.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-04-16T11:12:37Z
      DOI: 10.1177/1759720X211006959
      Issue No: Vol. 13 (2021)
  • Serum-derived extracellular vesicles inhibit osteoclastogenesis in
           active-phase patients with SAPHO syndrome
    • Authors: Yanpan Gao, Yanyu Chen, Lun Wang, Chen Li, Wei Ge
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Objective:Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic inflammatory disorder and the underlying pathogenesis is unclear. In this study, 88 SAPHO patients and 118 healthy controls were recruited to investigate the role of serum-derived extracellular vesicles (SEVs) in SAPHO syndrome.Methods:Quantitative proteomics was applied for SEVs proteome identification, and ELISA and Western blotting was performed to verify the results of mass spectrum data. In vitro osteoclastogenesis and osteogenesis assay was used to confirm the effects of SEVs on bone metabolism.Results:Tandem mass tagging-based quantitative proteomic analysis of SAPHO SEVs revealed differential expressed proteins involved in bone metabolism. Of these, serum amyloid A-1 (SAA1) and C-reactive protein (CRP) were upregulated. Higher SAA1 levels in SAPHO patients were confirmed by ELISA. In addition, SAA1 levels were positively correlated with CRP, an inflammatory marker related to the condition of patients. In vitro celluler studies confirmed that SAPHO SEVs inhibited osteoclastogenesis in patients mainly in the active phase of the disease. Further analysis demonstrated that Nucleolin was upregulated in osteoclasts of active-phase patients under SAPHO SEVs stimulation.Conclusion:In this study, we identified SAA1 as an additional inflammation marker that can potentially assist the diagnosis of SAPHO syndrome, and speculated that Nucleolin is a key regulator of osteoclastogenesis in active-phase patients.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-04-16T11:10:21Z
      DOI: 10.1177/1759720X211006966
      Issue No: Vol. 13 (2021)
  • Prevalence, therapy and tumour response in patients with rheumatic
           immune-related adverse events following immune checkpoint inhibitor
           therapy: a single-centre analysis
    • Authors: Sophia H. Verspohl, Tobias Holderried, Charlotte Behning, Peter Brossart, Valentin S. Schäfer
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Background:Immune checkpoint inhibitors (ICIs) improved cancer therapy by inducing a higher immune system activity. This effect can cause rheumatic immune-related adverse events (rh-irAEs), which have not yet been extensively studied.Methods:We analysed 437 patients between 2014 and 2019, treated with ipilimumab (anti-CTLA-4) and/or nivolumab (anti-PD-1) or pembrolizumab (anti-PD-1) at the Clinic for Internal Medicine III, Oncology, Haematology and Rheumatology at the University Hospital Bonn, Germany.Results:Of the 437 patients 60% were males. Patients were mainly treated for melanoma, lung cancer, head and neck tumour and urothelial carcinoma. At least one immune-related adverse event (irAE) was observed in 163 patients (37.3%), including rh-irAE. Most common side effects were rash, colitis and hepatitis. We identified 19 patients (4.3%) with a minimum of one rh-irAE due to ICI therapy; three of those had a pre-existing rheumatic disease. Arthralgia developed most frequently in eight patients (42.1%). Other rh-irAEs were: arthritis (n = 7; distinguished in rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis and undifferentiated arthritis), myalgia (n = 2) and myositis (n = 3). Most rh-irAEs were classified as moderately severe (Common Terminology Criteria of Adverse Events grade 2: 68.4%). Median time between starting ICI therapy and the occurrence of rh-irAE was 109 days (interquartile range 40–420 days). Fifteen patients (78.9%) were treated with glucocorticosteroids. In four cases additional therapy with methotrexate or tocilizumab was required. Even though patients benefited from ICI treatment, therapy had to be discontinued in six of the participants due to rh-irAE. Interestingly, patients with rh-irAE had a significantly higher tumour response compared with patients without rh-irAE (94.4% versus 43.5%; p 
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-04-13T06:36:27Z
      DOI: 10.1177/1759720X211006963
      Issue No: Vol. 13 (2021)
  • Factors affecting drug survival of an alternative TNF inhibitor and
           secukinumab in patients with ankylosing spondylitis switching from the
           first TNF inhibitor
    • Authors: Oh Chan Kwon, Jung Hwan Park, Min-Chan Park
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Background:To investigate factors associated with drug survival of an alternative tumour necrosis factor inhibitor (TNFi) and secukinumab (SEC) after switching from the first TNFi in patients with ankylosing spondylitis (AS).Methods:We included a total of 78 patients with AS who switched to an alternative TNFi (n = 56) or SEC (n = 22) from the first TNFi. Patient characteristics at the time of switching and drug discontinuation rate were compared between the two groups. Cox regression analyses were performed to evaluate factors associated with the risk of discontinuing the alternative TNFi and SEC.Results:The proportion of patients with syndesmophytes was numerically lower (28.6% versus 45.5%, p = 0.155) and the C-reactive protein (CRP) level was numerically higher [3.8 (1.0–15.4) mg/L versus 1.1 (0.5–3.5) mg/L, p = 0.060] in patients who received an alternative TNFi. The drug discontinuation rate (alternative TNFi: 35.7% versus SEC: 36.4%, p = 0.957) and reasons for discontinuation were similar (primary failure, p = 0.342; secondary failure, p > 0.999; and adverse events, p = 0.670) between the two groups. A higher CRP level at switching was associated with a lower risk (adjusted HR = 0.93, 95% CI = 0.87–0.99, p = 0.022) of discontinuing the alternative TNFi, and primary failure of the first TNFi was associated with a higher risk [adjusted HR (HR) = 5.20, 95% confidence interval (CI) = 1.91–14.11, p = 0.001]. Current smokers (adjusted HR = 5.77, 95% CI = 1.20–27.74, p = 0.029) and the presence of syndesmophytes (adjusted HR = 7.49, 95% CI = 1.39–40.23, p = 0.019) were associated with a higher risk of discontinuing SEC.Conclusion:When switching the drug from the first TNFi in patients with AS, an alternative TNFi could be preferable in patients with higher CRP levels or syndesmophytes, or current smokers, whereas SEC could be a better choice in patients who presented primary failure of the first TNFi in terms of drug survival.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-04-13T06:36:17Z
      DOI: 10.1177/1759720X211009021
      Issue No: Vol. 13 (2021)
  • Concomitant beta-blocker use is associated with a reduced rate of
           remission in patients with rheumatoid arthritis treated with
           disease-modifying anti-rheumatic drugs: a post hoc multicohort analysis
    • Authors: Ahmad Y. Abuhelwa, David J. R. Foster, Arkady Manning-Bennett, Michael J. Sorich, Susanna Proudman, Michael D. Wiese, Ashley M. Hopkins
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Background:Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease associated with increased risk of cardiovascular disease (CVD). Treatment for CVD may involve pharmacological agents that antagonise beta adrenergic receptors. These receptors may play an important role in immunology, and the effects of beta-blockers (BB) in RA is unknown. The aim of this study was to investigate the association between BB use and remission in patients with RA initiating tocilizumab +/− conventional synthetic (cs-) DMARD therapy.Methods:Data was pooled from five randomised trials investigating tocilizumab and/or csDMARD treatment in RA (primarily methotrexate). The association between BB use and remission according to the Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) was assessed by Cox proportional hazard analysis. Sensitivity analysis in patients with pre-existing CVD and an exploratory analysis of the impact of other CVD drugs were conducted.Results:Data were available from 5502 participants, 594 (10.8%) of whom were using systemic BB. BB use was associated with less frequent SDAI remission in the total [adjusted hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.57–0.87, p = 0.001] and CVD cohort [adjusted HR 0.72 (0.57–0.90, p = 0.005)]. The association was consistent between trials (interaction p = 0.44) and treatment arms (interaction p = 0.06). No significant association between remission and β1-receptor selectivity was identified (p = 0.16), and the association was independent from other cardiovascular drug use. Similar associations between BB use and CDAI remission were observed.Conclusion:In a large, pooled cohort of RA patients initiating csDMARDs and/or tocilizumab, BB use was independently associated with less frequent remission.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-04-13T06:36:02Z
      DOI: 10.1177/1759720X211009020
      Issue No: Vol. 13 (2021)
  • The importance of maternal pregnancy vitamin D for offspring bone health:
           learnings from the MAVIDOS trial
    • Authors: Rebecca J. Moon, Elizabeth M. Curtis, Stephen J. Woolford, Shanze Ashai, Cyrus Cooper, Nicholas C. Harvey
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Optimisation of skeletal mineralisation in childhood is important to reduce childhood fracture and the long-term risk of osteoporosis and fracture in later life. One approach to achieving this is antenatal vitamin D supplementation. The Maternal Vitamin D Osteoporosis Study is a randomised placebo-controlled trial, the aim of which was to assess the effect of antenatal vitamin D supplementation (1000 IU/day cholecalciferol) on offspring bone mass at birth. The study has since extended the follow up into childhood and diversified to assess demographic, lifestyle and genetic factors that determine the biochemical response to antenatal vitamin D supplementation, and to understand the mechanisms underpinning the effects of vitamin D supplementation on offspring bone development, including epigenetics. The demonstration of positive effects of maternal pregnancy vitamin D supplementation on offspring bone development and the delineation of underlying biological mechanisms inform clinical care and future public-health policies.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-04-08T10:31:54Z
      DOI: 10.1177/1759720X211006979
      Issue No: Vol. 13 (2021)
  • Associations between glucocorticoids, antiphospholipid antibodies and
           femur head necrosis in patients with SLE: a directed acyclic graph-based
           multicentre study
    • Authors: Shengbao Chen, Qianying Cai, Yanjun Xu, Qiong Fu, Yong Feng, Xiaoxiang Chen, Shengming Dai, Dongbao Zhao, Ce Zhan, Weidong Xu, Jiwei Wang, Yang Wang, Jinming Yu, Chunde Bao, Changqing Zhang
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Background:Osteonecrosis of the femoral head (ONFH) remains a major cause of disability in patients with systemic lupus erythematosus (SLE) and seriously impairs quality of life. This study aimed to investigate associations between glucocorticoids (GCs), antiphospholipid antibodies (aPLs), and ONFH in patients with SLE.Methods:We conducted a multicentre cohort study on patients with SLE and used a directed acyclic graph-based analysis strategy. Details of GC therapy, aPLs status, other drug administration and other SLE-related characteristics were collected. ONFH occurrence during follow-up was determined by magnetic resonance imaging. Multivariable logistic regression and generalized estimating equation models were performed to assess their effects on ONFH, and a simplified scoring system comprising these factors for short- and medium-term SLE-ONFH prediction was developed by receiver operating characteristic curve analysis.Results:Of 449 SLE patients with a median follow-up duration of 5.3 years, 41 (9.1%) developed ONFH. Independently risk factors of SLE-ONFH including: average daily GC dose with an adjusted odds ratio (aOR) of 1.1 and 95% confidence interval (CI) of 1.0–1.1; GC therapy duration (3–5 years: aOR 3.3, 95% CI 1.4–7.8; >5 years: aOR 8.0, 95% CI 3.3–19.4); initial intravenous GC (aOR 4.4, 95% CI 1.9–10.1); positive aPLs (aOR 2.8, 95% CI 1.4–5.8); and Arterial hypertension secondary to GC usage (aOR 5.2, 95% CI 1.4–19.1). And we successfully developed the simplified scoring system (SCORE model) with an area under the curve of 0.88 (95% CI 0.82–0.94).Conclusion:Based on the risk factors involved in the development of SLE-ONFH, a novel SCORE model was developed, which might be helpful for risk stratification of SLE-ONFH in clinical practice.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-03-29T10:25:31Z
      DOI: 10.1177/1759720X211002677
      Issue No: Vol. 13 (2021)
  • Cycling of tumor necrosis factor inhibitors versus switching to different
           mechanism of action therapy in rheumatoid arthritis patients with
           inadequate response to tumor necrosis factor inhibitors: a Bayesian
           network meta-analysis
    • Authors: Alberto Migliore, Giuseppe Pompilio, Davide Integlia, Joe Zhuo, Evo Alemao
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Introduction:For patients with rheumatoid arthritis (RA) with an inadequate response to tumor necrosis factor inhibitors (TNFi), main options include cycling onto a different TNFi or switching to a biologic/targeted synthetic disease-modifying antirheumatic drug with a different mechanism of action (MOA). This network meta-analysis (NMA) assessed comparative clinical efficacy of cycling versus switching.Methods:We conducted a literature search in MEDLINE, Embase, and Cochrane Library. Outcomes included proportion of patients with 20%, 50%, or 70% response to American College of Rheumatology criteria (ACR20/ACR50/ACR70 response), Disease Activity Score in 28 joints (DAS28) score below 2.6 or between 2.6 and 3.2, mean change in DAS28 score, mean reduction in and proportion of patients achieving a clinically meaningful reduction (⩾0.22) in Health Assessment Questionnaire score, number of serious adverse events (AEs), and withdrawals for any reason/due to AEs/lack of treatment efficacy. To account for the wide range of study populations and designs, we developed three models to conduct the NMA: fixed-effect, random-effects, and hierarchical Bayesian. PROSPERO ID: CRD42019122993.Results:We identified nine randomized controlled trials and 16 observational studies. The fixed-effect model suggested a 0.99 probability that switch was the better strategy for increasing odds of a clinically meaningful improvement in ACR50 [odds ratio (OR): 1.35 (95% credible interval (CI): 0.96–1.81)]. The fixed-effect model also suggested that switch was associated with lower rates of withdrawal for any reasons [OR: 0.53 (95% CI: 0.40–0.68)]. The random-effects and hierarchical Bayesian models suggested additional uncertainty as they considered more variability than the fixed-effect model.Discussion:Results suggest that switching to a drug with a different MOA is more effective and associated with lower rates of withdrawal than cycling to a different TNFi after failure of first-line TNFi. Further trials that directly compare cycling with switching are warranted to better assess comparative efficacy.Plain language summaryAssessment of the effectiveness of different drug treatment strategies in patients with rheumatoid arthritis: an analysis of the published literatureRheumatoid arthritis (RA) is a chronic disease in which inflammation affects joints along with the entire body; this may cause significant pain, joint damage, physical disability, a decreased quality of life, and an increased risk of death.Tumor necrosis factor inhibitors (TNFis) are a common choice as first-line drugs to treat RA. Although they are effective in many patients, therapy with a TNFi is not successful within the first year of treatment in approximately one-third of patients due to either a lack of efficacy or safety issues.When TNFi therapy is unsuccessful, the options are to “cycle” to another TNFi or to “switch” to another drug with a different mechanism of action (MOA). Further studies are needed to help doctors decide the best treatment strategy for their patients when treatment with an initial TNFi fails.This study analyzed 25 published studies in which patients were either “cycled” to another TNFi or “switched” to a drug with a different MOA after unsuccessful treatment with an initial TNFi.The results showed that “switching” to a drug with a different MOA was a better treatment strategy than “cycling” to another TNFi; “switching” increased the chance of clinically meaningful improvement in disease status and lowered the chance of having to stop treatment for any reason.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-03-29T10:20:48Z
      DOI: 10.1177/1759720X211002682
      Issue No: Vol. 13 (2021)
  • Moving toward targeting the right phenotype with the right platelet-rich
           plasma (PRP) formulation for knee osteoarthritis
    • Authors: Isabel Andia, Leire Atilano, Nicola Maffulli
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Intra-articular injections of platelet-rich plasma (PRP) and other novel blood-derived products developed specifically for osteoarthritis (OA) can provide pain relief and potential benefits in disease progression. Meta-analyses show the clinical superiority of PRP compared with other intra-articular injections, but results are modest and the effect sizes are small. PRP injections in knee OA are performed indiscriminately, but the clinical response varies enormously between patients because of an array of mixed OA phenotypes. Subgroup analyses are scarce; some studies stratify patients according to radiographic severity and found better results in early OA, without consensus for more advanced stages of the condition. Parallel identification of soluble and imaging biomarkers is essential to personalise and leverage PRP therapies. The inflammatory phenotype is most interesting from the PRP perspective because PRPs modulate inflammation by releasing a large pool of chemokines and cytokines, which interact with synovial fibroblasts and macrophages; in addition, they can modulate the innate immune response. No soluble biomarkers have been discovered that have implications for OA research and PRP interventions. Clinical examination of patients based on their inflammatory phenotype and imaging identification of pain sources and structural alterations could help discern who will respond to PRP. Synovial inflammation and bone marrow lesions are sources of pain, and intra-articular injections of PRP combined with subchondral bone injection can enhance clinical outcomes. Further refining ultrasound phenotypes may aid in personalising PRP therapies. Intra-articular delivery combined with injections in altered ligamentous structures, medial and coronal ligaments or premeniscal pes anserinus showed positive clinical outcomes. Although the evidence supporting these approaches are weak, they merit further consideration to refine PRP protocols and target the right OA phenotypes.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-03-29T10:16:47Z
      DOI: 10.1177/1759720X211004336
      Issue No: Vol. 13 (2021)
  • Reduction of anterior uveitis flares in patients with axial
           spondyloarthritis on certolizumab pegol treatment: final 2-year results
           from the multicenter phase IV C-VIEW study
    • Authors: Irene E. van der Horst-Bruinsma, Rianne E. van Bentum, Frank D. Verbraak, Atul Deodhar, Thomas Rath, Bengt Hoepken, Oscar Irvin-Sellers, Karen Thomas, Lars Bauer, Martin Rudwaleit
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Introduction:Acute anterior uveitis (AAU), affecting up to 40% of patients with axial spondyloarthritis (axSpA), risks permanent visual deficits if not adequately treated. We report 2-year results from C-VIEW, the first study to prospectively investigate certolizumab pegol (CZP) on AAU in patients with active axSpA at high risk of recurrent AAU.Patients and methods:C-VIEW (NCT03020992) was a 104-week (96 weeks plus 8-week safety follow-up), open-label, multicenter study. Eligible patients had active axSpA, human leukocyte antigen-B27 (HLA-B27) positivity and a history of recurrent AAU (⩾2 AAU flares in total; ⩾1 in the year prior to baseline). Patients received CZP 400 mg at weeks 0, 2 and 4, then 200 mg every 2 weeks to week 96. The primary efficacy endpoint was the AAU flare event rate during 96 weeks’ CZP versus 2 years pre-baseline.Results:Of 115 enrolled patients, 89 initiated CZP (male: 63%; radiographic/non-radiographic axSpA: 85%/15%; mean disease duration: 9.1 years); 83 completed week 96. There was a significant 82% reduction in AAU flare event rate during CZP versus pre-baseline [rate ratio (95% confidence interval): 0.18 (0.12–0.28), p 
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-03-29T10:15:07Z
      DOI: 10.1177/1759720X211003803
      Issue No: Vol. 13 (2021)
  • Early anti IL-1 treatment replaces steroids in refractory Kawasaki
           disease: clinical experience from two case reports
    • Authors: Maria Vincenza Mastrolia, Giulia Abbati, Claudia Signorino, Ilaria Maccora, Edoardo Marrani, Ilaria Pagnini, Gabriele Simonini
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Refractory Kawasaki disease (KD) is related to a major risk of coronary arteries abnormalities and its treatment is not standardized. In this regard, anakinra (ANA), an interleukin (IL)-1 receptor antagonist, represents an emerging therapeutic option. We report two cases of children, diagnosed with KD, nonresponsive to two doses of intravenous immunoglobulins, successfully treated with ANA, without a prior use of steroids. Patient 2 developed a coronary dilatation, that improved significantly after ANA therapy. Our experience highlights IL-1 blockade effectiveness in reducing KD inflammation and suggests ANA adoption as second-line therapy, with a timesaving and steroid-sparing strategy. Our results, combined with the evidence of the IL-1 key role in KD and coronary arteritis pathogenesis and to the recent clinical evidence reported by the KAWAKINRA trial, encourage an earlier recourse to ANA in patients with refractory KD, in order to fight inflammation, and to treat and prevent the development of coronary artery aneurysms. Further studies are needed to better define the place of IL-1 blockade in KD step-up treatment.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-03-29T10:12:47Z
      DOI: 10.1177/1759720X211002593
      Issue No: Vol. 13 (2021)
  • A comparison of clinical examination and ultrasound enthesitis indices in
           patients with psoriatic arthritis, adjusted for concomitant fibromyalgia
    • Authors: Mark Sapsford, Jobie Evans, Gavin Clunie, Deepak Jadon
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Objectives:To: (a) determine the extent of ultrasound (US)-detected peripheral enthesitis in a cohort of patients with psoriatic arthritis (PsA); (b) compare this with three clinical examination (CE) enthesitis indices; and (c) determine the effect of concurrent fibromyalgia on the evaluation of enthesitis.Methods:A prospective single-centre cross-sectional study of consecutive outpatients with established PsA undergoing clinical examination for enthesitis and US examination for inflammatory and structural lesions of enthesitis. Multivariable analyses tested for association between US scores, CE enthesitis indices and influence of concurrent fibromyalgia.Results:A total of 106 patients were assessed. Of these, 91/106 (85.8%) had CE enthesitis and 105/106 (99.1%) had ⩾1 US feature of enthesitis. There was a moderate correlation between US entheseal inflammation and both the Leeds Enthesitis Index (LEI) (Spearman rank, r = 0.36) and Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC) (r = 0.44). US entheseal damage did not correlate with CE enthesitis indices. Twenty-eight (26.4%) patients were classified as having concurrent fibromyalgia, in whom multivariable regression analyses demonstrated no correlation between US scores and CE enthesitis indices. PsA patients without fibromyalgia demonstrated a statistically significant association between both LEI (r = 0.48, p 
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-03-29T10:11:10Z
      DOI: 10.1177/1759720X211003812
      Issue No: Vol. 13 (2021)
  • Influence of colchicine prescription in COVID-19-related hospital
           admissions: a survival analysis
    • Authors: Alfredo Madrid-García, Inés Pérez, José Ignacio Colomer, Leticia León-Mateos, Juan A Jover, Benjamín Fernández-Gutiérrez, Lydia Abásolo-Alcazar, Luis Rodríguez-Rodríguez
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Aims:To analyze the association between colchicine prescription and COVID-19-related hospital admissions in patients with rheumatic and musculoskeletal diseases (RMDs).Methods:Patients attending a rheumatology outpatient clinic from a tertiary care center in Madrid, Spain, from 1 September 2019 to 29 February 2020 were included. Patients were assigned as exposed or unexposed based on whether they were prescribed with colchicine in their last visit to the clinic during the 6 months before the start of the observation period. Treatment changes during the observation period were also considered. The primary outcome was COVID-19-related hospital admissions between 1 March and 20 May 2020. Secondary outcome included COVID-19-related mortality. Several weighting techniques for data balancing, based and non-based on the propensity score, followed by Cox regressions were performed to estimate the association of colchicine prescription on both outcomes.Discussion:The number of patients entered in the study was 9379, with 406 and 9002 exposed and unexposed follow-up periods, respectively. Generalized Boosted Models (GBMs) and Empirical Balancing Calibration Weighting (EBCW) methods showed the best balance for COVID-19-related hospital admissions. Colchicine prescription did not show a statistically significant association after covariable balancing (p-value = 0.195 and 0.059 for GBM and EBCW, respectively). Regarding mortality, the low number of events prevented a success variable balancing and analysis.Conclusion:Colchicine prescription does not play a significant protective or risk role in RMD patients regarding COVID-19-related hospital admissions. Our observations could support the maintenance of colchicine prescription in those patients already being treated, as it is not associated with a worse prognosis.Plain language title:Colchicine influence in COVID-19-related hospital admissions
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-03-26T10:39:24Z
      DOI: 10.1177/1759720X211002684
      Issue No: Vol. 13 (2021)
  • Comparative efficacy and safety of Janus kinase inhibitors and biological
           disease-modifying antirheumatic drugs in rheumatoid arthritis: a
           systematic review and network meta-analysis
    • Authors: Chenghua Weng, Leixi Xue, Qing Wang, Wentian Lu, Jiajun Xu, Zhichun Liu
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Objective:To evaluate the comparative efficacy and safety of Janus kinase (JAK) inhibitors and biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) and an inadequate response to at least one disease-modifying antirheumatic drug (DMARD).Methods:PubMed, Embase, Cochrane library and were searched for relevant randomized controlled trials (RCTs) from inception to April 2020. The active drugs included three JAK inhibitors and eight bDMARDs while the control drugs included placebo or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Outcomes include American College of Rheumatology 20% response (ACR20), Disease Activity Score in 28 joints (DAS28), Health Assessment Questionnaire–Disability Index (HAQ-DI) and discontinuations for adverse events (AEs). We estimated summary odds ratios (ORs) and weighted mean differences (WMDs) using network meta-analysis with random effects.Results:Eighty-eight RCTs with 31,566 patients were included. All JAK inhibitors and bDMARDs were more effective than placebo in ACR20 (ORs ranging between 3.05 and 5.61), DAS28 (WMDs ranging between −1.91 and −0.80) and HAQ-DI (WMDs ranging between −0.34 and −0.21). Tocilizumab, certolizumab pegol and upadacitinib showed relatively good efficacy in these three outcomes according to their relative ranking. Notably, tocilizumab was more effective than other active drugs in DAS28 (WMDs ranging between −1.11 and −0.49). Compared with the lower recommended doses, increasing the doses of JAK inhibitors (baricitinib 4 mg versus 2 mg, tofacitinib 10 mg versus 5 mg and upadacitinib 30 mg versus 15 mg) cannot provide significant additional benefits. In terms of discontinuations for AEs, all active drugs showed no significant difference compared with placebo except certolizumab pegol [OR 1.65, 95% credible interval (CrI) 1.06–2.61] and rituximab (3.17, 1.11–10.80).Conclusions:Tocilizumab, certolizumab pegol and upadacitinib may have relatively good efficacy in patients with RA after treatment failure with csDMARDs. RA patients taking a JAK inhibitor may have a preference for a lower recommended dose.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-03-22T05:38:06Z
      DOI: 10.1177/1759720X21999564
      Issue No: Vol. 13 (2021)
  • Ultrasound for diagnosis and follow-up of chronic axillary vasculitis in
           patients with long-standing giant cell arteritis
    • Authors: Philipp Bosch, Christian Dejaco, Wolfgang A. Schmidt, Kenny D-. Schlüter, Gudrun Pregartner, Valentin S. Schäfer
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Aims:To assess intima-media thickness (IMT) changes measured by ultrasound in axillary arteries of giant cell arteritis (GCA) patients over time and to calculate an ultrasound cut-off value for the diagnosis of chronic axillary artery involvement in patients with longstanding GCA.Methods:Ultrasound of both axillary arteries was performed in 109 GCA patients at time of diagnosis and at several follow-up visits and in 40 healthy controls (HCs). IMT determined at the prospective follow-up visit was compared between GCA patients with (axGCA) and without (non-axGCA) vasculitis of axillary arteries at baseline, as well as with HCs. Changes in IMT were depicted. Receiver operating characteristics were performed for cut-off calculations. Inter-/intra-rater agreement was evaluated using stored images and intraclass correlation coefficient (ICC).Results:Seventy-three patients were in the axGCA and 36 in the non-axGCA group. Pathological IMT of axillary arteries (axGCA) declined in the first 18 months of treatment by −0.5 mm, (range −2.77 to 0.50), independent of age and gender. Median IMT, after median disease duration of 48 months (16–137), was 0.90 mm (0.46–2.20) in axGCA and 0.60 mm (0.42–1.0) in the non-axGCA group pooled with HCs. An IMT of 0.87 mm was highly specific (specificity 96%, sensitivity 61%) for diagnosis of chronic axGCA. Intra-rater and inter-reader agreement of ultrasound images were good [ICC 0.96–1.0 (three readers) and 0.87, respectively].Conclusion:Pathological IMT of the axillary artery declined under treatment. An IMT of 0.87 mm is highly specific for diagnosis of chronic vasculitis of axillary arteries in long-standing GCA patients.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-03-19T10:22:42Z
      DOI: 10.1177/1759720X21998505
      Issue No: Vol. 13 (2021)
  • Impact of sarcopenia on rehabilitation outcomes after total knee
           replacement in older adults with knee osteoarthritis
    • Authors: Chun-De Liao, Hung-Chou Chen, Shih-Wei Huang, Tsan-Hon Liou
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Introduction:Knee osteoarthritis (KOA) is associated with an increased risk of sarcopenia, and aging-related muscle deterioration continues after total knee replacement (TKR). Low skeletal muscle mass index may influence postoperative rehabilitation outcomes. Through this study, we aimed to investigate the impact of preoperative sarcopenia on clinical outcomes after postoperative rehabilitation in older Asian adults.Methods:A total of 190 older adults (39 men, 151 women) were enrolled from two previous trials and were classified as having no sarcopenia, class I sarcopenia, or class II sarcopenia according to definitions provided by the Asian Working Group for Sarcopenia (AWGS) and the European Working Group on Sarcopenia in Older People (EWGSOP). All patients were retrospectively analyzed before (T0) and after (T1) TKR rehabilitation and 10 months after surgery (T2). The outcome measures included the timed up-and-go test (TUGT), gait speed (GS), timed chair rise (TCR), and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical difficulty (WOMAC-PF). With patient characteristics and T0 scores as covariates, an analysis of variance was performed to identify intergroup differences in changes of all outcome measures at T1 and T2.Results:According to the definitions of both the AWGS and EWGSOP, patients with class I and class II sarcopenia exhibited minor changes in TUGT, GS, TCR, and WOMAC-PF at T1 and T2 (all p  0.05).Conclusions:Sarcopenia independently had negative impacts on the treatment effects of rehabilitation on physical mobility but not on pain outcome after TKR in older adults with KOA.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-03-12T10:18:04Z
      DOI: 10.1177/1759720X21998508
      Issue No: Vol. 13 (2021)
  • Prevalence of axial spondyloarthritis in patients with inflammatory bowel
           disease using cross-sectional imaging: a systematic literature review
    • Authors: Jobie Evans, Mark Sapsford, Scott McDonald, Kenneth Poole, Tim Raine, Deepak R. Jadon
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Background:Patients with inflammatory bowel disease (IBD) have an excess burden of axial spondyloarthritis (axSpA), which, if left untreated, may significantly impact on clinical outcomes. We aimed to estimate the prevalence of axSpA, including previously undiagnosed cases, in IBD patients from studies involving cross-sectional imaging and identify the IBD features potentially associated with axSpA.Methods:PubMed, Embase and Cochrane databases were searched systematically between 1990 and 2018. Article reference lists and key conference abstract lists from 2012 to 2018 were also reviewed. All abstracts were reviewed by two authors to determine eligibility for inclusion. The study inclusion criteria were (a) adults aged 18 years or above, (b) a clinical diagnosis of IBD and (c) reporting identification of sacroiliitis using cross-sectional imaging.Results:A total of 20 observational studies were identified: 12 used CT, 6 used MR and 2 utilised both computed tomography (CT) and magnetic resonance (MR) imaging. Sample sizes ranged from 25 to 1247 (a total of 4096 patients); 31 studies were considered to have low selection bias, 13 included two or more radiology readers, and 3 included rheumatological assessments. The prevalence of sacroiliitis, the most commonly reported axSpA feature, ranged from 2.2% to 68.0% with a pooled prevalence of 21.0% [95% confidence interval (CI) 17–26%]. Associated IBD features include increasing IBD duration, increasing age, male sex, IBD location, inflammatory back pain and peripheral arthritis. No significant difference in the prevalence of sacroiliitis between Crohn’s disease and ulcerative colitis was identified. Study limitations include variability in the individual study sample sizes and patient demographics.Conclusion:This review highlights the need for larger, well-designed studies using more sensitive imaging modalities and multivariable modelling to better estimate the prevalence of axSpA in IBD. An improved knowledge of the IBD phenotype(s) associated with axSpA and use of cross-sectional imaging intended for IBD assessment to screen for axSpA may help clinicians identify those patients most at risk.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-03-11T09:43:10Z
      DOI: 10.1177/1759720X21996973
      Issue No: Vol. 13 (2021)
  • Psoriatic arthritis and the association with cardiometabolic disease: a
           narrative review
    • Authors: Paras Karmacharya, Alexis Ogdie, Lihi Eder
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Psoriatic arthritis (PsA) is associated with a higher burden of cardiometabolic disorders, such as hypertension, dyslipidemia, diabetes, obesity, and cardiovascular disease (CVD), compared with the general population. These comorbidities are associated with the severity of disease, and adversely affect treatment outcomes in PsA. Comorbidities lead to increased physician visits and medications for patients and make the selection and maintenance of therapies challenging for physicians. Moreover, CVD is a leading cause of mortality in PsA. Therefore, optimal management of PsA should include not only treating the skin and joint disease, but also identifying comorbidities early, and managing them to improve long-term outcomes. Further studies are needed to understand the complex mechanisms, interactions, and trajectories of cardiometabolic comorbidities in psoriatic disease.Plain Language SummaryPsoriatic arthritis and the association with cardiometabolic diseasePsoriatic arthritis (PsA) is associated with a higher incidence and prevalence of cardiometabolic comorbidities compared with the general population, and higher than psoriasis and other inflammatory arthritides, such as rheumatoid arthritis and other spondyloarthritides.Obesity and hyperlipidemia are associated with an increased risk of developing PsA.Cardiometabolic comorbidities in PsA are associated with more severe disease and a lower likelihood of response to therapy.Suggested approaches to improve screening and management of CVD in PsA include education of family physicians and relevant specialists, development of mechanisms to improve communication between the rheumatologists and primary care providers, and novel models of care, including interdisciplinary cardio-rheumatology clinics.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-03-03T06:37:57Z
      DOI: 10.1177/1759720X21998279
      Issue No: Vol. 13 (2021)
  • Pathophysiology of musculoskeletal pain: a narrative review
    • Authors: Filomena Puntillo, Mariateresa Giglio, Antonella Paladini, Gaetano Perchiazzi, Omar Viswanath, Ivan Urits, Carlo Sabbà, Giustino Varrassi, Nicola Brienza
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Musculoskeletal pain (excluding bone cancer pain) affects more than 30% of the global population and imposes an enormous burden on patients, families, and caregivers related to functional limitation, emotional distress, effects on mood, loss of independence, and reduced quality of life. The pathogenic mechanisms of musculoskeletal pain relate to the differential sensory innervation of bones, joints, and muscles as opposed to skin and involve a number of peripheral and central nervous system cells and mediators. The interplay of neurons and non-neural cells (e.g. glial, mesenchymal, and immune cells) amplifies and sensitizes pain signals in a manner that leads to cortical remodeling. Moreover, sex, age, mood, and social factors, together with beliefs, thoughts, and pain behaviors influence the way in which musculoskeletal pain manifests and is understood and assessed. The aim of this narrative review is to summarize the different pathogenic mechanisms underlying musculoskeletal pain and how these mechanisms interact to promote the transition from acute to chronic pain.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-02-26T09:32:30Z
      DOI: 10.1177/1759720X21995067
      Issue No: Vol. 13 (2021)
  • Epidemiology of cardiac or orthopedic procedures in gout versus rheumatoid
           arthritis: a national time-trends study
    • Authors: Jasvinder A. Singh, John Cleveland
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Aims:To examine the secular trends in the number and rates of in-hospital cardiac and orthopedic procedures in people with gout and rheumatoid arthritis (RA), and the United States (US) general population, from 1998 to 2014.Methods:We examined the frequency of seven common cardiac and orthopedic procedures in hospitalized people with gout, RA, or the general population using the 1998–2014 US National Inpatient Sample (NIS). Poisson regression evaluated the differences in frequencies in 1998 versus 2014, between gout and RA, and within each cohort.Results:Both in-hospital cardiac and orthopedic procedures increased in gout and RA with time, in contrast with declining cardiac procedures in the general US population. Cardiac procedures were significantly higher in gout versus RA in 1998 (59% higher) and 2014 (92% higher). The rate of cardiac procedures increased from 36.6 to 82.8 in gout and from 20.1 to 33.1 in RA per 100,000 NIS claims from 1998 to 2014. Orthopedic procedures became more common than cardiac procedures in gout and RA by 2014. In RA, the cardiac–orthopedic procedure volume difference was significant in 1998 and 2014. We noted no significant difference between cardiac versus orthopedic procedures in 1998 in gout, but the difference was significant in 2014. Orthopedic procedures in gout were significantly lower than RA in 1998 (33% lower), but were significantly higher than RA in 2014 (5% higher).Conclusion:Increasing in-hospital cardiac procedures in gout and RA contrasting with declining general US population rates indicated that optimal management of systemic inflammation and an early diagnosis of gout and RA are needed. The rate of increase in orthopedic procedures exceeded that in cardiac procedures. A much greater volume and rate of increase in common in-hospital cardiac and orthopedic procedures in gout compared to RA indicates that an aggressive approach to treat-to-target in gout is needed to potentially reduce the associated healthcare burden and cost.Plain language summaryCardiac and orthopedic procedures rising faster for gout compared to rheumatoid arthritis in the United StatesWe performed a national US study of the most common cardiac versus orthopedic procedures from 1998 to 2014. We found that over time, the number and the rate of cardiac procedures increased in people with gout (2.2-fold higher) or rheumatoid arthritis (1.6-fold higher). This was surprising, since during the same time, we noted a decrease in cardiac procedures in the general U.S. population. The rate of cardiac procedures in gout was 2.5-fold higher than that in rheumatoid arthritis, 82.8 vs. 33.1 per 100,000 NIS claims in 2014. Interestingly, orthopedic procedures were more common than cardiac procedures in both gout and RA in all periods. Also, the difference in the numbers of cardiac vs. orthopedic procedures increased over time in both gout and RA. Gout outpaced rheumatoid arthritis for both the total number and the rate of cardiac or orthopedic procedures over time. Therefore, our study provides an understanding of an increasing procedure burden in gout compared to rheumatoid arthritis, and to the general U.S. people with these conditions.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-02-26T05:10:16Z
      DOI: 10.1177/1759720X20973916
      Issue No: Vol. 13 (2021)
  • How much does fat mass change affect serum uric acid levels among
           apparently clinically healthy Korean men'
    • Authors: Joong Kyong Ahn, Jiwon Hwang, Mi Yeon Lee, Mira Kang, Junghye Hwang, Eun-Mi Koh, Hoon-Suk Cha
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Objective:The aim of this study was to examine the impact of fat mass alteration on serum uric acid (SUA) levels in apparently clinically healthy men.Methods:We evaluated 27,387 men who consecutively underwent health check ups between 2015 and 2017. We assessed the likelihood of achieving a SUA level of
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-02-24T12:20:45Z
      DOI: 10.1177/1759720X21993253
      Issue No: Vol. 13 (2021)
  • A warning machine learning algorithm for early knee osteoarthritis
           structural progressor patient screening
    • Authors: Hossein Bonakdari, Afshin Jamshidi, Jean-Pierre Pelletier, François Abram, Ginette Tardif, Johanne Martel-Pelletier
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Aim:In osteoarthritis (OA) there is a need for automated screening systems for early detection of structural progressors. We built a comprehensive machine learning (ML) model that bridges major OA risk factors and serum levels of adipokines/related inflammatory factors at baseline for early prediction of at-risk knee OA patient structural progressors over time.Methods:The patient- and gender-based model development used baseline serum levels of six adipokines, three related inflammatory factors and their ratios (36), as well as major OA risk factors [age and bone mass index (BMI)]. Subjects (677) were selected from the Osteoarthritis Initiative (OAI) progression subcohort. The probability values of being structural progressors (PVBSP) were generated using our previously published prediction model, including five baseline structural features of the knee, i.e. two X-rays and three magnetic resonance imaging variables. To identify the most important variables amongst the 47 studied in relation to PVBSP, we employed the ML feature classification methodology. Among five supervised ML algorithms, the support vector machine (SVM) demonstrated the best accuracy and use for gender-based classifiers development. Performance and sensitivity of the models were assessed. A reproducibility analysis was performed with clinical trial OA patients.Results:Feature selections revealed that the combination of age, BMI, and the ratios CRP/MCP-1 and leptin/CRP are the most important variables in predicting OA structural progressors in both genders. Classification accuracies for both genders in the testing stage (OAI) were >80%, with the highest sensitivity of CRP/MCP-1. Reproducibility analysis showed an accuracy ⩾92%; the ratio CRP/MCP-1 demonstrated the highest sensitivity in women and leptin/CRP in men.Conclusion:This is the first time that such a framework was built for predicting knee OA structural progressors. Using this automated ML patient- and gender-based model, early prediction of knee structural OA progression can be performed with high accuracy using only three baseline serum biomarkers and two risk factors.Plain language summaryMachine learning model for early knee osteoarthritis structural progressionKnee osteoarthritis is a well-known debilitating disease leading to reduced mobility and quality of life – the main causes of chronic invalidity. Disease evolution can be slow and span many years; however, for some individuals, the progression/evolution can be fast. Current treatments are only symptomatic and conventional diagnosis of osteoarthritis is not very effective in early identification of patients who will progress rapidly. To improve therapeutic approaches, we need a robust prediction model to stratify osteoarthritis patients at an early stage according to risk of joint structure disease progression.We hypothesize that a prediction model using a machine learning system would enable such an early identification of individuals for whom osteoarthritis knee structure will degrade rapidly. Data were from the Osteoarthritis Initiative, a National Institute of Health (United States) databank, and the robustness and generalizability of the developed model was further evaluated using osteoarthritis patients from an external cohort. Using the supervised machine learning system (support vector machine), we developed an automated patient- and gender-based model enabling an early clinical prognosis for individuals at high risk of structural progressive osteoarthritis. In brief, this model employed at baseline (when the subject sees a physician) easily obtained features consisting of the two main osteoarthritis risk factors, age and bone mass index (BMI), in addition to the serum levels of three molecules. Two of these molecules belong to a family of factors names adipokines and one to a related inflammatory factor. In brief, the model comprising a combination of age, BMI, and the ratios CRP/MCP-1 and leptin/CRP were found very robust for both genders, and the high accuracy persists when tested with an external cohort conferring the gender-based model generalizability. This study offers a new automated system for identifying early knee osteoarthritis structural progressors, which will significantly improve clinical prognosis with real time patient monitoring.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-02-23T12:55:03Z
      DOI: 10.1177/1759720X21993254
      Issue No: Vol. 13 (2021)
  • Mesenchymal stromal cell products for intra-articular knee injections for
           conservative management of osteoarthritis
    • Authors: Isabel Andia, Nicola Maffulli
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Sports injuries and secondary joint problems, mainly of the knee, are common, especially in sports associated with high impact activities and/or torsional loading. The consequences can be career ending in elite athletes and reduce exercise activities in recreational people. Various cell products can be injected intra-articularly. First, fresh cellular mixtures can be prepared and injected in the same day, such as stromal vascular fraction of adipose tissue (SVF) and bone marrow concentrates (BMCs). Second, autologous mesenchymal stromal cells (MSCs) can be isolated from BMCs or SVF and, after several weeks of laboratory expansion, several millions of MSCs can be obtained for intra-articular injection. Finally, allogeneic MSCs from the bone marrow, adipose tissue or perinatal tissues of selected donors constitute an ‘off-the-shelf’ experimental treatment for injection delivery in patients with osteoarthritis of the knee. The perceived efficacy of all these products is based on the hypothesis of a paracrine mechanism of action: when living cells are delivered within the joint, they establish a molecular cross-talk with immune cells and local cell phenotypes, thereby modulating inflammation with subsequent modifications in the catabolic/degenerative milieu. Current clinical research examines whether injection delivery of MSCs translates into actual clinical benefits. Overall, clinical studies lack the quality needed to answer major research questions, including clinical and structural efficacy, optimal cell dose, and number of injections and specific protocol for cell delivery. Poor experimental designs are exacerbated by the diversity of patient phenotypes that hinder comparisons between treatments. Further understanding of disease pathology is paramount to develop potent function assays and understand whether the host tissue, the cell product or both should be primed before MSCs are injected intra-articularly.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-02-19T06:03:19Z
      DOI: 10.1177/1759720X21996953
      Issue No: Vol. 13 (2021)
  • Cyclin-dependent kinase 7 (CDK7) is an emerging prognostic biomarker and
           therapeutic target in osteosarcoma
    • Authors: Hangzhan Ma, Dylan C. Dean, Ran Wei, Francis J. Hornicek, Zhenfeng Duan
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Background:Overexpression of cyclin-dependent kinase 7 (CDK7) is a well-known pathogenic feature of various malignancies and a sign of a more dismal prognosis. As relatively little is known about CDK7 in osteosarcoma, we elected to evaluate its expression, prognostic value, and function.Methods:We began by analyzing the publicly available data sets on CDK7 expression, including RNA sequencing data from the Therapeutically Applicable Research to Generate Effective Treatments on Osteosarcoma (TARGET-OS) and the Gene Expression database of Normal and Tumor tissues 2 (GENT2). The correlation between patient tissue CDK7 expression and their clinicopathological features and prognosis was assessed via immunohistochemical staining of a unique tissue microarray constructed from osteosarcoma specimens. Furthermore, we analyzed CDK7 expression in osteosarcoma cell lines and tissues by Western blot. CDK7-specific siRNA and a highly-selective CDK7 inhibitor, BS-181, were applied to determine the function of CDK7 on osteosarcoma cell growth and proliferation. In addition, the effect of CDK7 inhibition on clonogenicity was evaluated using a clonogenic assay, and a 3D cell culture model was used to mimic CDK7 effects in an in vivo environment.Results:Our results demonstrate that higher CDK7 expression significantly correlates with recurrence, metastasis, and shorter overall survival in osteosarcoma patients. Therapeutically, we show that CDK7 knockdown with siRNA or selective inhibition with BS-181 decreases proliferation and induces apoptosis of osteosarcoma cells.Conclusion:This study supports CDK7 overexpression as an independent predictor of poor prognosis and promising therapeutic target for osteosarcoma.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-02-19T06:02:59Z
      DOI: 10.1177/1759720X21995069
      Issue No: Vol. 13 (2021)
  • Update on the therapeutic management of patients with either psoriatic
           arthritis or ulcerative colitis: focus on the JAK inhibitor tofacitinib
    • Authors: Maria Sole Chimenti, Paola Conigliaro, Livia Biancone, Roberto Perricone
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Psoriatic arthritis (PsA) and ulcerative colitis (UC) are immune-mediated diseases that cause significant burden worldwide. Recent advances in their management have improved patient outcomes. However, significant unmet needs still remain as not all patients respond to current treatments, and patients may lose responsiveness over time. An improved understanding of the pathophysiology of these diseases has brought about the development of novel disease-modifying agents, including interleukin inhibitors and, more recently, Janus kinase (JAK) inhibitors. With the approval of tofacitinib for the treatment of adults with active PsA and in adult patients with moderately-to-severely active UC, JAK inhibitors have recently entered the treatment armamentarium for PsA and UC. A number of other JAK inhibitors are also undergoing clinical development and are currently in phase III trials. This review provides an overview of the current therapeutic options for PsA and UC, with a focus on the JAK inhibitors.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-02-19T06:02:42Z
      DOI: 10.1177/1759720X20977777
      Issue No: Vol. 13 (2021)
  • Is central sensitization an important determinant of functional disability
           in patients with chronic inflammatory arthritides'
    • Authors: Giovanni Adami, Elisabetta Gerratana, Fabiola Atzeni, Camilla Benini, Elisabetta Vantaggiato, Denise Rotta, Luca Idolazzi, Maurizio Rossini, Davide Gatti, Angelo Fassio
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Background:Central sensitization (CS) is a condition characterized by a disproportionate response to pain stimuli. We sought to investigate the prevalence of CS in patients with inflammatory arthritides and its association with measures of disease activity and functional disability.Methods:We conducted an observational retrospective study in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) patients. We administered to all the subjects in the study the CS inventory (CSI), a questionnaire that has been used for the diagnosis of CS. Demographic and clinical characteristics were collected as well as measures or disease activity [i.e. Simple Disease Activity Index, Disease Activity Score in PsA (DAPSA)] and functional disability [Health Assessment Questionnaire Disability Index (HAQ-DI)]. Patients with fibromyalgia were excluded from the analyses. The primary outcome measure was the presence of functional disability as assessed by HAQ-DI >1.Results:We enrolled 150 patients with inflammatory arthritides (78 PsA and 72 RA). Prevalence of CS was observed in 35.3% of the overall sample (29% in RA, 42.9% in PsA). Binary logistic regressions showed a strong, independent and linear association between functional disability and CS in both PsA and RA patients. The strength of this association was greater in PsA than in RA.Conclusion:CS is an important determinant of functional disability in patients with chronic inflammatory arthritides. PsA appeared to be more vulnerable to CS. In addition, in the presence of CS, DAPSA did not adequately capture the occurrence of functional disability. Therefore, special attention should be paid to PsA patients, in whom the concomitant diagnosis of CS should be routinely ruled out.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-02-15T12:01:05Z
      DOI: 10.1177/1759720X21993252
      Issue No: Vol. 13 (2021)
  • Cardiovascular risk factors are negatively associated with rheumatoid
           arthritis disease outcomes
    • Authors: Kangping Cui, Mohammad Movahedi, Claire Bombardier, Bindee Kuriya
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Aims:Rheumatoid arthritis (RA) is associated with cardiovascular disease (CVD), but the influence of CVD risk factors on RA outcomes is limited. We examined if CVD risk factors alone are associated with RA disease activity and disability.Methods:We performed a cross-sectional analysis of participants in the Ontario Best Practices Research Initiative, RA registry. Patients were categorized into mutually exclusive CVD categories: (1) No established CVD and no CVD risk factors; (2) CVD risk factors only including ⩾1 of hypertension, dyslipidemia, diabetes, or smoking; or (3) history of established CVD event. Multivariable regression analyses examined the effect of CVD status on Disease Activity Score 28 (DAS28-ESR), Clinical Disease Activity Index (CDAI), and Health Assessment Questionnaire Disability Index (HAQ-DI) scores at baseline.Results:Of 2033 patients, 50% had at least 1 CVD risk factor, even in the absence of established CVD. The presence of ⩾1 CVD risk factor was independently associated with higher CDAI [β coefficient 1.59, 95% confidence interval (CI) 0.29–2.90, p = 0.02], DAS28-ESR (β coefficient 0.20, 95% CI 0.06–0.34, p = 0.01) and HAQ-DI scores (β coefficient 0.15, 95% CI 0.08–0.22, p 1 CVD risk factor was associated with higher disease activity and disability, compared with having one or no CVD risk factors.Conclusion:CVD risk factors alone, or in combination, are associated with higher disease activity and disability in RA. This emphasizes the importance of risk factor recognition and management, not only to prevent CVD, but also to improve potential RA outcomes.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-02-15T12:00:47Z
      DOI: 10.1177/1759720X20981217
      Issue No: Vol. 13 (2021)
  • The value of anti-CarP and anti-PAD4 as markers of rheumatoid arthritis in
           ACPA/RF negative rheumatoid arthritis patients
    • Authors: Bogdan Kolarz, Marek Ciesla, Ann K. Rosenthal, Magdalena Dryglewska, Maria Majdan
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Background:Anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF) are key factors in the American College of Rheumatology/European League Against Rheumatism rheumatoid arthritis (RA) classification criteria markers. However, about 30% of patients diagnosed with RA are seronegative, rationalizing the need for new serologic markers for RA. Antibodies against carbamylated proteins (anti-CarP) and against peptidyl-arginine deiminase type 4 (anti-PAD4) have been postulated to be useful RA markers. The purpose of this study is to evaluate the value of anti-CarP and anti-PAD4 in a well-characterized population of RA patients and healthy controls (HCs).Methods:A total of 122 RA patients and 30 HCs were enrolled in the study. Serum levels of ACPA, anti-PAD4, anti-CarP and RF were determined by enzyme-linked immunosorbent immunoassays (ELISAs). Synthetic carbamylated peptides were used in the ELISA assay to determine the protein targets of the anti-CarP antibodies.Results:Rates of ACPA, RF, anti-PAD4 and anti-CarP positivity were 85.2%, 67.2%, 55.7% and 46.7% in RA, and 0%, 0%, 6.7% and 6.7% in HC respectively. In the RA population, 25.4% of patients had all four types of antibodies positive, while 6.6% had no antibodies. There was a significant correlation between anti-PAD4 and ACPAs (rs = 0.39), RF and ACPAs, (rs = 0.3) and RF and anti-CarP, (rs = 0.3). There was no correlation between ACPAs and anti-CarP. Anti-CarP positivity was noted in 49 (47.1%) and 45 (54.9%) of ACPAs and RF positive patients respectively. In addition, five anti-CarP+ patients did not have ACPA nor RF.Conclusion:Anti-CarP but not anti-PAD4 may be a useful biomarker in identifying ACPA/RF negative RA patients. This antibody may identify an additional RA population who may benefit from early implementation of aggressive therapy.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-02-11T12:43:01Z
      DOI: 10.1177/1759720X21989868
      Issue No: Vol. 13 (2021)
  • Hospital admissions in inflammatory rheumatic diseases during the peak of
           COVID-19 pandemic: incidence and role of disease-modifying agents
    • Authors: Benjamin Fernandez-Gutierrez, Leticia Leon, Alfredo Madrid, Luis Rodriguez-Rodriguez, Dalifer Freites, Judit Font, Arkaitz Mucientes, Esther Culebras, Jose Ignacio Colome, Juan Angel Jover, Lydia Abasolo
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Aims:In this pandemic, it is essential for rheumatologists and patients to know the relationship between COVID-19 and inflammatory rheumatic diseases (IRDs). We wanted to assess the role of targeted synthetic or biologic disease-modifying antirheumatic drugs (ts/bDMARDs) and other variables in the development of moderate-severe COVID-19 disease in IRD.Methods:An observational longitudinal study was conducted during the epidemic peak in Madrid (1 March to 15 April 2020). All patients attended at the rheumatology outpatient clinic of a tertiary hospital in Madrid with a medical diagnosis of IRD were included. Main outcome: hospital admission related to COVID-19. Independent variable: ts/bDMARDs. Covariates: sociodemographic, comorbidities, type of IRD diagnosis, glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Incidence rate (IR) of hospital admission related to COVID-19 was expressed per 1000 patient-months. Cox multiple regression analysis was run to examine the influence of ts/bDMARDs and other covariates on IR of hospital admission related to COVID-19.Results:A total of 3951 IRD patients were included (5896 patient-months). Methotrexate was the csDMARD most used. Eight hundred and two patients were on ts/bDMARDs, mainly anti-TNF agents, and Rtx. Hospital admissions related to COVID-19 occurred in 54 patients (1.36%) with an IR of 9.15 (95% confidence interval: 7–11.9). In the multivariate analysis, older, male, comorbidities, and specific systemic autoimmune conditions (Sjögren, polychondritis, Raynaud, and mixed connective tissue disease) had more risk of hospital admissions. Exposition to ts/bDMARDs did not achieve statistical significance. Use of glucocorticoids, NSAIDs, and csDMARDs dropped from the final model.Conclusion:This study provides additional evidence in IRD patients regarding susceptibility to moderate–severe infection related to COVID-19.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-02-05T04:47:22Z
      DOI: 10.1177/1759720X20962692
      Issue No: Vol. 13 (2021)
  • Sustained clinical response and safety of etanercept in patients with
           early axial spondyloarthritis: 10-year results of the ESTHER trial
    • Authors: Fabian Proft, Anja Weiß, Murat Torgutalp, Mikhail Protopopov, Valeria Rios Rodriguez, Hildrun Haibel, Olaf Behmer, Joachim Sieper, Denis Poddubnyy
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Aims:Long-term data on TNFi treatment in patients with axSpA is scarce. The objective of this analysis was to assess long-term clinical efficacy of etanercept in early axSpA [including both non-radiographic and radiographic axSpA forms], who participated in the long-term (until year 10) extension of the ESTHER-trial.Methods:In the previously reported ESTHER-trial, patients with early active axSpA were randomized to treatment with etanercept (n = 40) or sulfasalazine (n = 36) during the first year. Patients in remission discontinued their therapy and were followed up until the end of year 2; in case of remission-loss, etanercept was (re)-introduced and continued until the end of year 10. If remission was not achieved at year 1, patients continued receiving (or were switched to) etanercept for up to 10 years.Results:A total of 19 patients (12 with r-axSpA and 7 with nr-axSpA at baseline) out of the initial 76 patients (= 25%) completed year 10 of the study. In the entire group, a sustained clinical response was seen over 10 years of follow up in the as-observed analysis. Completers were significantly more often male and showed lower values of patient and physician global assessments of disease activity, Ankylosing Spondylitis Disease Activity Score (ASDAS), and Ankylosing Spondylitis Quality of Life questionnaire (ASQoL) scores at baseline as compared with non-completers. When analyzing clinical data of the completers, mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) values were constantly below 2 and mean ASDAS below 2.1 during follow up with no statistically significant differences between the r-axSpA and nr-axSpA subgroups. A total of 39 serious adverse events were documented over the 10 years, while six of them were seen as possibly associated with the etanercept treatment, which led in five patients to treatment discontinuation.Conclusion:A sustained clinical response was observed over the 10 years of the study with comparable response and drop-out rates between r-axSpA and nr-axSpA. Etanercept was well tolerated across the entire treatment period and showed a good safety profile with no new safety signals.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-01-29T08:51:55Z
      DOI: 10.1177/1759720X20987700
      Issue No: Vol. 13 (2021)
  • A theoretical framework to improve the construct for chronic pain
           disorders using fibromyalgia as an example
    • Authors: Dinesh Kumbhare, Luigi Tesio
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Fibromyalgia (FM) is a frequent, complex condition of chronic musculoskeletal pain with no evidence for biological correlates. For this reason, despite many efforts from the medical community, its construct still appears ill defined. Promising candidate biomarkers are critically reviewed. A research agenda is proposed for developing a clearer construct of FM. The ideal theoretical framework is one of overcoming the illness–disease dichotomy and considering reciprocal interactions between biology and behaviour. This approach may foster research in other fields of pain medicine and of medicine in general.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-01-28T11:44:08Z
      DOI: 10.1177/1759720X20966490
      Issue No: Vol. 13 (2021)
  • The frequency of occult solid malignancy in patients with polymyalgia
           rheumatica-like symptoms
    • Authors: André Ramon, Caroline Guillibert-Karras, Laurence Milas-Julien, Jean-François Garrot, Jean-Francis Maillefert, Paul Ornetti
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Aims:We aim to evaluate the clinical usefulness of systematic screening for occult cancer in patients with polymyalgia rheumatic (PMR)-like symptoms in real-life practice.Methods:All patients seen by rheumatologists in Burgundy, France, between March 2016 and December 2018 for new-onset PMR that met the 2012 ACR/EULAR classification criteria were prospectively included. Patients underwent systematic screening including determination of the erythrocyte sedimentation rate, serum C-reactive protein levels, thoracic, abdominal and pelvic computed tomography (CT-TAP) and, in men, serum prostate-specific antigen. The standardized incidence ratio (SIR) for cancers was calculated using 2012 national estimates of cancer incidence. Potential predictive factors for the diagnosis of cancer were then evaluated using univariate and multivariate analyses.Results:Among the 118 patients included, nine cases of cancer were confirmed and diagnosed with CT-TAP: kidney carcinoma (n = 4), lung cancer (n = 2), pancreatic, colon, and ampullary carcinoma (n = 1 each). Among these cancers, five were localized (four kidney, and one ampullary carcinoma) and were treated with complete surgical resection. The expected incidence of cancer in the general population was 1.95, leading to an overall SIR of 4.6 (95% CI 2.4–8.9, p 
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-01-27T07:13:10Z
      DOI: 10.1177/1759720X20984275
      Issue No: Vol. 13 (2021)
  • Tumour necrosis factor inhibitor tapering in patients with ankylosing
           spondylitis at low disease activity: factors associated with flare
    • Authors: Oh Chan Kwon, Jung Hwan Park, Min-Chan Park
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Background:To investigate factors associated with flare in patients with ankylosing spondylitis (AS) who tapered tumour necrosis factor inhibitors (TNFis) after achievement of low disease activity (LDA) with the standard dose of TNFis.Methods:This retrospective cohort study included 101 patients with AS who tapered their first TNFis after achievement of LDA. The proportion of reduced versus standard doses of TNFi throughout the follow up in each patient was quantified using the time-averaged dose quotient (DQ). Clinical characteristics were compared between patients who did and did not experience flare after TNFi tapering. Multivariable Cox regression analysis was performed to identify factors associated with flare. Receiver operating characteristic curve analysis was performed to determine the cut-offs of these covariates that best predicted flare.Results:Of the total 101 patients, 45 (44.6%) patients experienced flare after TNFi tapering. Compared with patients who did not experience flare, those who experienced flare had a shorter disease duration (p = 0.006), shorter LDA duration before TNFi tapering (p 
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-01-22T06:43:29Z
      DOI: 10.1177/1759720X20986732
      Issue No: Vol. 13 (2021)
  • The role of ixekizumab in non-radiographic axial spondyloarthritis
    • Authors: Bon San Koo, Tae-Hwan Kim
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 13, Issue , January-December 2021.
      Among patients with axial spondyloarthritis (axSpA), non-radiographic axial spondyloarthritis (nr-axSpA) is distinguished from ankylosing spondylitis (AS) by a lack of obvious radiographic changes in the sacroiliac joint. Tumor necrosis factor inhibitor (TNFi) has been used as a highly effective treatment in patients with AS and has shown good efficacy and safety in clinical trials in patients with nr-axSpA. As the pathophysiological mechanism for axSpA has started to become better recognized, various drugs other than TNFi, all of which are related to the interleukin-17 (IL-17) axis, are being evaluated in patients with axSpA. IL-17 inhibitors, such as secukinumab and ixekizumab, are effective drugs for patients with AS. A recent clinical trial reported that ixekizumab, a monoclonal antibody against IL-17A, was also effective in patients with nr-axSpA. In a COAST-X study, ixekizumab was superior to a placebo for improving signs and symptoms in patients with nr-axSpA at weeks 16 and 52. The adverse events were no different from those found in previous ixekizumab studies, and no new safety signals were identified. However, when considering several IL-17 inhibitors, it is necessary to obtain sufficient data to identify the exacerbation of extra-articular manifestation. In terms of effectiveness and safety, ixekizumab may be an appropriate alternative to TNFi in nr-axSpA patients.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2021-01-13T06:49:34Z
      DOI: 10.1177/1759720X20986734
      Issue No: Vol. 13 (2021)
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
Tel: +00 44 (0)131 4513762

Your IP address:
Home (Search)
About JournalTOCs
News (blog, publications)
JournalTOCs on Twitter   JournalTOCs on Facebook

JournalTOCs © 2009-