Steroid induced osteonecrosis: An analysis of steroid dosing risk.

Osteonecrosis is a serious condition involving bone destruction that frequently requires surgical treatment to rebuild the joint. While there is an abundance of literature documenting corticosteroid related osteonecrosis, there is no consensus as to the relative risk of osteonecrosis after administration of steroids via parenteral, oral, topical, inhaled and other routes. This risk is an important prognostic indicator because identification and conservative intervention can potentially reduce morbidity associated with aggressive surgical treatment of osteonecrosis. This paper provides insight into establishing guidelines related to the risk of developing osteonecrosis as a result of corticosteroid use. Case studies, retrospective studies and prospective studies in humans on different corticosteroids and varied dosages were assessed. Most cases of osteonecrosis are secondary to systemically administered corticosteroids and/or high dose daily therapy, particularly in patients with underlying comorbidities including connective tissue diseases, hyperlipidemia, or previous trauma. Previous case reports of osteonecrosis related to inhaled or topical use of steroids are complicated by the fact that in the great majority of cases, the patients are also treated with systemic steroids prior to the development of osteonecrosis. Based on the literature, a set of recommendations regarding the risk of osteonecrosis in patients on steroids was formulated

A programme for risk assessment and minimisation of progressive multifocal leukoencephalopathy developed for vedolizumab clinical trials

Introduction Over the past decade, the potential for drug-associated progressive multifocal leukoencephalopathy (PML) has become an increasingly important consideration in certain drug development programmes, particularly those of immunomodulatory biologics. Whether the risk of PML with an investigational agent is proven (e.g. extrapolated from relevant experience, such as a class effect) or merely theoretical, the serious consequences of acquiring PML require careful risk minimisation and assessment. No single standard for such risk minimisation exists. Vedolizumab is a recently developed monoclonal antibody to α4β7 integrin. Its clinical development necessitated a dedicated PML risk minimisation assessment as part of a global preapproval regulatory requirement. Objective The aim of this study was to describe the multiple risk minimisation elements that were incorporated in vedolizumab clinical trials in inflammatory bowel disease patients as part of the risk assessment and minimisation of PML programme for vedolizumab. Methods A case evaluation algorithm was developed for sequential screening and diagnostic evaluation of subjects who met criteria that indicated a clinical suspicion of PML. An Independent Adjudication Committee provided an independent, unbiased opinion regarding the likelihood of PML. Results Although no cases were detected, all suspected PML events were thoroughly reviewed and successfully adjudicated, making it unlikely that cases were missed. Conclusion We suggest that this programme could serve as a model for pragmatic screening for PML during the clinical development of new drugs

Oncologic Emergencies: Immune-Based Cancer Therapies and Complications

Cancer therapies have undergone several recent advancements. Current cancer treatments include immune-based therapies comprised of checkpoint inhibitors, and adoptive immunotherapy; each treatment has the potential for complications that differ from chemotherapy and radiation. This review evaluates immune-based therapies and their complications for emergency clinicians. Therapy complications include immune-related adverse events (irAE), cytokine release syndrome (CRS), autoimmune toxicity, and chimeric antigen receptor (CAR) T-cell-related encephalopathy syndrome (CRES). Immune-related adverse events are most commonly encountered with checkpoint inhibitors and include dermatologic complications, pneumonitis, colitis/diarrhea, hepatitis, and endocrinopathies. Less common irAEs include nephritis, myocardial injury, neurologic toxicity, ocular diseases, and musculoskeletal complications. CRS and CRES are more commonly associated with CAR T-cell therapy. CRS commonly presents with flu-like illness and symptoms resembling sepsis, but severe myocardial and pulmonary disease may occur. Critically ill patients require resuscitation, broad-spectrum antibiotics, and hematology/oncology consultation

Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: fundamentals of care for uveitis (focus) initiative

Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic reviewof the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE,CINAHL,SCOPUS,BIOSIS, andWeb of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review.Atotal of 44 globally representativegroupmembersmet in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents

Analgesic Management of Pain in Elite Athletes: A Systematic Review

Objective: To identify the prevalence, frequency of use, and effects of analgesic pain management strategies used in elite athletes. Design: Systematic literature review. Data Sources: Six databases: Ovid/Medline, SPORTDiscus, CINAHL, Embase, Cochrane Library, and Scopus. Eligibility Criteria for Selecting Studies: Empirical studies involving elite athletes and focused on the use or effects of medications used for pain or painful injury. Studies involving recreational sportspeople or those that undertake general exercise were excluded. Main Results: Of 70 articles found, the majority examined the frequency with which elite athletes use pain medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, anesthetics, and opioids. A smaller set of studies assessed the effect of medications on outcomes such as pain, function, and adverse effects. Oral NSAIDs are reported to be the most common medication, being used in some international sporting events by over 50% of athletes. Studies examining the effects of pain medications on elite athletes typically involved small samples and lacked control groups against which treated athletes were compared. Conclusions: Existing empirical research does not provide a sufficient body of evidence to guide athletes and healthcare professionals in making analgesic medication treatment decisions. Based on the relatively robust evidence regarding the widespread use of NSAIDs, clinicians and policymakers should carefully assess their current recommendations for NSAID use and adhere to a more unified consensus-based strategy for multidisciplinary pain management in elite athletes. In the future, we hope to see more rigorous, prospective studies of various pain management strategies in elite athletes, thus enabling a shift from consensus-based recommendations to evidence-based recommendations

Appropriateness and efficacy of Spa therapy for musculoskeletal disorders. A Delphi method consensus initiative among experts in Italy.

OBJECTIVE: The aim of the study was to identify the main aspects concerning appropriateness and efficacy of Spa therapy for musculoskeletal pathologies. METHODS: A committee of 8 experts from Italian universities, public hospitals, territorial services, research institutes and patient associations was set up. Clinicians from Italian medical centers specialized in rheumatology, rehabilitation and thermal medicine took part in a Delphi process aimed at obtaining consensus statements among the participants. RESULTS: Large consensus was obtained for statements grouped under the following main themes: treatment indications; choice of treatment modality and treatment efficacy. CONCLUSIONS: The experts developed a number of consensus statements which may be used as a practical reference to guide the choice of physicians to treat musculoskeletal diseases with Spa therapy

How to do it: Vitamin D supplementation

Vitamin D testing and supplementation is of great interest to neurologists and their patients. Recommended nutritional intakes of vitamin D in the UK remain focused on bone health, despite increasing evidence for a role outside this area. Here we discuss how neurologists might approach vitamin D testing and supplementation, focusing on two conditions associated with vitamin D deficiency that have an increased risk of downstream complications resulting from these: multiple sclerosis and epilepsy. We set out a rationale for testing serum 25-hydroxyvitamin D concentrations and discuss our personal practice in terms of supplementation, with evidence where available

Lidocaine for systemic sclerosis: a double-blind randomized clinical trial

Background: Systemic sclerosis (scleroderma; SSc) is an orphan disease with the highest case-specific mortality of any connective-tissue disease. Excessive collagen deposit in affected tissues is a key for the disease's pathogenesis and comprises most of the clinical manifestations. Lidocaine seems to be an alternative treatment for scleroderma considering that: a) the patient's having excessive collagen deposits in tissues affected by scleroderma; b) the patient's demonstrating increased activity of the enzyme prolyl hydroxylase, an essential enzyme for the biosynthesis of collagen; and c) lidocaine's reducing the activity of prolyl hydroxylase. the aim of this study was to evaluate the efficacy and safety of lidocaine in treating scleroderma.Methods: A randomized double-blind clinical trial included 24 patients with scleroderma randomized to receive lidocaine or placebo intravenously in three cycles of ten days each, with a one-month interval between them. Outcomes: cutaneous (modified Rodnan skin score), oesophageal (manometry) and microvascular improvement (nailfold capillaroscopy); improvement in subjective self-assessment and in quality of life (HAQ).Results: There was no statistically significant difference between the groups for any outcome after the treatment and after 6-months follow-up. Improvement in modified Rodnan skin score occurred in 66.7% and 50% of placebo and lidocaine group, respectively (p = 0.408). Both groups showed an improvement in subjective self-assessment, with no difference between them.Conclusions: Despite the findings of a previous cohort study favouring the use of lidocaine, this study demonstrated that lidocaine at this dosage and means of administration showed a lack of efficacy for treating scleroderma despite the absence of significant adverse effects. However, further similar clinical trials are needed to evaluate the efficacy of lidocaine when administered in different dosages and by other means.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Brazilian Cochrane Ctr, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Discipline Emergency Med & Evidence Based Med, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Discipline Rheumatol, São Paulo, BrazilUniv Santo Amaro, Discipline Rheumatol, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Brazilian Cochrane Ctr, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Discipline Emergency Med & Evidence Based Med, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Discipline Rheumatol, São Paulo, BrazilFAPESP: 01-13895-9Web of Scienc

Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination.

Abstract OBJECTIVE: We characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination. METHODS: We evaluated clinical phenotypes, annualised relapse rates (ARR) prior and on immunotherapy and Expanded Disability Status Scale (EDSS), in 218 demyelinating episodes from 33 paediatric and 26 adult patients. RESULTS: The most common initial presentation in the cohort was optic neuritis (ON) in 54% (bilateral (BON) 32%, unilateral (UON) 22%), followed by acute disseminated encephalomyelitis (ADEM) (20%), which occurred exclusively in children. ON was the dominant phenotype (UON 35%, BON 19%) of all clinical episodes. 109/226 (48%) MRIs had no brain lesions. Patients were steroid responsive, but 70% of episodes treated with oral prednisone relapsed, particularly at doses <10\u2009mg daily or within 2 months of cessation. Immunotherapy, including maintenance prednisone (P=0.0004), intravenous immunoglobulin, rituximab and mycophenolate, all reduced median ARRs on-treatment. Treatment failure rates were lower in patients on maintenance steroids (5%) compared with non-steroidal maintenance immunotherapy (38%) (P=0.016). 58% of patients experienced residual disability (average follow-up 61 months, visual loss in 24%). Patients with ON were less likely to have sustained disability defined by a final EDSS of 652 (OR 0.15, P=0.032), while those who had any myelitis were more likely to have sustained residual deficits (OR 3.56, P=0.077). CONCLUSION: Relapsing MOG antibody-associated demyelination is strongly associated with ON across all age groups and ADEM in children. Patients are highly responsive to steroids, but vulnerable to relapse on steroid reduction and cessation

Bone health in patients with multiple sclerosis relapses

OBJECTIVES: To evaluate the bone health and vitamin D levels of a cohort of patients with relapses of multiple sclerosis (MS) and to propose an algorithm for the management of bone health in this patient group. METHODS: We prospectively studied 56 consecutive patients from our acute relapse clinic. 3 patients were excluded from analysis as they were not deemed to have experienced an acute MS relapse. Bone health was assessed with vitamin D levels and Dual Energy X-ray Absorptiometry (DEXA) scanning (10 patients failed to attend for DEXA). Statistical analyses were used to compare groups and identify predictive variables. A review of the literature led to a proposed management protocol. RESULTS: Pre-relapse the baseline EDSS was ≤6.5 in all subjects, and <4.0 in the majority (66%). Most received corticosteroids. 51% had low bone mineral density (BMD) as defined by a T-score less than −1.0 on DEXA scanning. Three were osteoporotic (T-score less than −2.5). Thirty one of fifty (62%) subjects were Vitamin D deficient (25(OH)D less than 50 nmol/L). A range of variables, including previous corticosteroid usage, were not significantly predictive of reduced BMD. CONCLUSIONS: There was a high frequency of both low BMD and Vitamin D deficiency in this cohort of relatively young and largely ambulatory patients experiencing MS relapses. Current tools, such as the WHO FRAX algorithm, are inadequate in assessing bone status and fracture risk in this patient group, predominantly as they are focused on older age groups. We propose a simple clinical management algorithm