A patient centered assessment of the 2016 ACR-EULAR Myositis Response Criteria: evaluating the meaningfulness of response.

OBJECTIVES: The ACR-EULAR Myositis Response Criteria (Total Improvement Score [TIS]) is a composite measure calculated using changes in myositis core set measures. It is unclear if achieving improvement per TIS reflects improvement in any symptoms of myositis patients. In this study, we examined the association between achieving TIS improvement and patient-centered outcome measures (PCOMs). METHODS: Adults with myositis were enrolled in a prospective study with baseline and 6-month visits. Six core set measures were collected at each visit along with the following PCOMs: Fatigue (visual analogue scale [VAS] and short form 36 [SF36]), pain (VAS, SF36), health-related quality of life (SF-36), physical function (PROMIS-physical function, SF36, sit-to-stand, timed up-and-go, and six-min walk) and physical activity (actigraphy). Mann-Whitney U was used to compare PCOMs between improvement groups. Spearman correlation and regression models were used for correlation and association between TIS and PCOMs, respectively. RESULTS: Of 50 patients (six polymyositis, 24 dermatomyositis, 9 necrotizing myopathy, 11 anti-synthetase syndrome) enrolled (mean age: 52, 60% female), 21 patients satisfied the TIS improvement criteria at 6-months. PCOMs including fatigue, pain, quality of life, physical activity and physical function demonstrated significantly greater improvement in patients who had minimal TIS improvement compared with those with no improvement. Greater PCOM improvements were seen with moderate-major TIS improvement. TIS correlated moderately-strongly with most PCOMs. CONCLUSION: Achieving improvement criteria was accompanied by significant clinical improvements in fatigue, pain, health-related quality of life, physical function, and physical activity. These results support the use of TIS as a clinically meaningful metric of improvement.

Nonsteroidal Anti-inflammatory Drugs vs Cognitive Behavioral Therapy for Arthritis Pain: A Randomized Withdrawal Trial.

Importance: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for knee osteoarthritis. However, they are associated with uncertain long-term clinical benefit and significant toxic effects. Objective: To evaluate whether discontinuing NSAIDs and engaging in a telephone-based cognitive behavioral therapy (CBT) program is noninferior to continuing NSAIDs for patients with knee osteoarthritis. Design, Setting, and Participants: The Stopping NSAIDs for Arthritis Pain multicenter randomized withdrawal trial was conducted for 364 patients taking NSAIDs for knee osteoarthritis pain on most days of the week for at least 3 months between September 1, 2013, and September 30, 2018. Analysis was performed on an intent-to-treat basis. Interventions: Participants discontinued their current NSAID and took 15 mg per day of meloxicam daily during a 2-week run-in period. Those who remained eligible were randomized in a 1:1 ratio to receive meloxicam or placebo for 4 weeks (blinded phase 1). Participants receiving meloxicam then continued this medication for 10 weeks, while those receiving placebo participated in a 10-week CBT program (unblinded phase 2). Main Outcomes and Measures: The primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at 4 weeks with the noninferiority margin set at 1. Secondary outcomes included the area under the curve of the pain score after 4 weeks as well as the WOMAC pain score, area under the curve of the pain score, WOMAC disability score, and global impression of change after treatment at 14 weeks. Results: A total of 180 participants (161 men; mean [SD] age, 58. 2 [11.8] years) were randomized to receive placebo followed by CBT, and a total of 184 participants (154 men; mean [SD] age, 58.5 [10.0] years) were randomized to receive meloxicam. After adjustment for baseline pain and study site, the estimated mean difference in WOMAC pain score between the placebo and meloxicam groups after 4 weeks was 1.4 (95% CI, 0.8-2.0; noninferiority test P = .92). At week 14, the adjusted mean difference in WOMAC pain score between the placebo (followed by CBT) and meloxicam groups was 0.8 (95% CI, 0.2-1.4; noninferiority P = .28). There was no statistically significant difference in the global impression of change (mean difference in scores, -0.2; 95% CI, -0.4 to 0.1; P = .15) or lower extremity disability (mean difference in scores, 0.9; 95% CI, -1.4 to 3.2; P = .45) between the 2 groups after 14 weeks. Conclusions and Relevance: Among patients with knee osteoarthritis, placebo and CBT (after placebo) are inferior to meloxicam. However, the WOMAC pain score differences between the 2 groups were small, and there were no statistically significant differences in participants' global impression of change or function after 14 weeks. Trial Registration: ClinicalTrials.gov Identifier: NCT01799213.

Characterisation of the nasal microbiota in granulomatosis with polyangiitis.

OBJECTIVES: Prior studies have suggested a potential link between nasal microbes and granulomatosis with polyangiitis (GPA; Wegener's), but these studies relied on culture-dependent methods. This study comprehensively examined the entire community of nasal microbiota (bacteria and fungi) in participants with GPA compared with healthy controls using deep sequencing methods. METHODS: 16S rRNA and internal transcribed spacer gene sequencing were performed on nasal microbial DNA isolated from nasal swabs of 60 participants with GPA and 41 healthy controls. Alpha and beta diversity were assessed as well as the relative abundance of the most abundant bacterial and fungal taxa. The effects of covariates including disease activity and immunosuppressive therapies on microbial composition were evaluated. RESULTS: Compared with controls, participants with GPA had a significantly different microbial composition (weighted UniFrac p=0.04) and lower relative abundance of Propionibacterium acnes and Staphylococcus epidermidis (for both, false discovery rate-corrected p=0.02). Disease activity in GPA was associated with a lower abundance of fungal order Malasseziales compared with participants with GPA in remission (p=0.04) and controls (p=0.01). Use of non-glucocorticoid immunosuppressive therapy was associated with 'healthy' nasal microbiota while participants with GPA who were off immunosuppressive therapy had more dysbiosis (weighted UniFrac p=0.01). No difference in the relative abundance of Staphylococcus aureus was observed between GPA and controls. CONCLUSIONS: GPA is associated with an altered nasal microbial composition, at both the bacterial and fungal levels. Use of immunosuppressive therapies and disease remission are associated with healthy microbial communities.

Intra cranial granulomatous disease in common variable immunodeficiency: Case series and review of the literature.

BACKGROUND/PURPOSE: Common variable immunodeficiency (CVID) is typically characterized by hypogammaglobulinemia and often but not always recurrent infections. Paradoxically, 8-22% of patients with CVID develop granulomatous disease. Granulomata have been described in many organs including the lungs, skin, liver, spleen, kidneys, eyes, lymph nodes, and intestines. Data about central nervous system (CNS) involvement in CVID are extremely rare. We aim to describe a case series and include an extensive literature review of CNS involvement in CVID to understand the different features and patterns of the disease. METHODS: We searched the English Pubmed database for relevant articles between 1950 and 2014 using the Key Words "common variable immunodeficiency", "granulomatous disease", "brain", "sarcoidosis", and "sarcoid-like syndrome". Data from all case series, surveys, systematic reviews, and individual case reports, as well as retrospective studies were extracted. A total of 15 patients were reported in the literature. We combined our experience with four additional patients from The Cleveland Clinic between 2009 and 2014. Demographics, clinical features, laboratory and imaging findings, treatment and follow-up were extracted for the 19 patients and summarized descriptively. RESULTS: Female sex and Caucasian race represented 63.2% (12/19), and 80% of the patients, respectively. The mean age of CVID diagnosis was 24 years; mean age when the CNS disease was diagnosed was 21.5 years. 68.4% of the patients (13/19) had granulomas involving ≥2 organs including the central nervous system, 31.6% (6/19) had CNS granulomas only. Associated granulomatous diseases occurred in lungs (72.7%), lymph nodes (27.2%), spleen (27.2%), eyes (18.1%), liver (18.1%), parotid glands (9%), and skin (9%). Fifty-three percent (10/19) of the patients had documented recurrent infections, all of them being upper respiratory tract infections. CNS manifestations included seizures (31.6%), headaches (21%), vision loss (15.7%), decreased cognition (10.5%), focal weakness (5.2%), nystagmus (5.2%), ataxia (5.2%), coma (5.2%), polyuria, and polydipsia (5.2%). Brain mass was the most common radiologic finding (70%) followed by leptomeningeal enhancement (10%), non-specific white matter lesions (10%) and absence of normal signal of the neurohypophysis (10%). Brain pathology was available in 12 patients: findings included granulomatous disease in 83.3%, angiocentric granulomas in 50%, vasculitis without granulomas in 8.3%, and lymphocytic infiltrate of the meninges with diffuse non-caseating granulomas in 8.3%. Cerebrospinal fluid analysis revealed elevated total proteins with/or without lymphocytic pleocytosis in 80%. CONCLUSION: CNS disease is a rare challenging complication of CVID. Patients with brain involvement are generally female, Caucasian, and likely have lung involvement. Although immunoglobulin and steroids remain the first line of treatment, other immunosuppressive agents have shown some promise with regards to recurrent relapsing presentations.

New-onset hepatitis C virus-associated glomerulonephritis following sustained virologic response with direct-acting antiviral therapy
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Glomerulonephritis (GN) is an important extra-hepatic manifestation of infection with hepatitis C virus (HCV). HCV-associated GN occurs due to HCV-induced lymphoproliferation, leading to the generation of pathogenic immune complexes, including complexes containing cryoglobulins. The management of HCV-associated extra-hepatic disease is focused on viral eradication, with direct-acting antiviral agents leading to high rates of sustained virologic remission. There have been a few reports of relapsing cryoglobulinemic vasculitis after sustained virologic remission was achieved with interferon-based therapies. This report presents two cases of new-onset HCV-associated GN that occurred after sustained virologic response was achieved with direct-acting antiviral (DAA) therapy.
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Successful use of Rituximab in a patient with recalcitrant multisystemic eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare eosinophil-rich disorder characterised by necrotising granulomatous inflammation affecting small to medium sized vessels. Extrapulmonary manifestations can be life-threatening when heart, central nervous system (CNS), gastrointestinal tract or kidneys are affected. We describe a case of a 56-year-old woman with a long-standing history of asthma, who presented with an acute sudden painless loss of vision after she had been recently diagnosed with EGPA and induced with pulse steroids and cyclophosphamide. The patient had a complicated hospital course with multisystemic involvement of active vasculitis, involving heart, kidneys, muscles, eyes and CNS. The patient's devastating condition responded remarkably to Rituximab. The role of Rituximab in EGPA is not yet proven. Few cases are reported in the literature about the role of Rituximab in EGPA, of which only one described retinal artery occlusion as a presentation of a recently treated patient with EGPA.

Depressive symptoms among surrogate decision makers in Lebanese ICUs.

Surrogate decision making is advocated to protect the vulnerable patient. Family members of patients in intensive care units (ICUs) are prone to develop depressive symptoms which may undermine their decisional capacity. Lebanon is a multicultural country where paternalism still dominates the physician-patient relationship and ethics are far from being the subject of research and studies. This multicenter observational study in the Greater Beirut area attempts to estimate the prevalence of depressive symptoms among surrogates deciding on behalf of ICU patients and to correlate their severity with sociodemographic factors. During the period March-May 2011, direct interviews were conducted and the Patient Health Questionnaire-9 (PHQ-9) was administered to 56 family members who had given consent, regarding therapeutic options, on behalf of ICU patients in seven university hospitals. We looked for relationships, in these surrogates, between severity of depression and age, sex, marital status, level of education, religion and status as the patient's spouse. The prevalence of major depression among surrogates was 61% using a cutoff of 10 on the PHQ-9 scale. Among the surrogates with depression, 15% had untreated moderate-to-severe depression. Severity of depression and suicidal ideation were not related to any of the studied factors. Depressive symptoms are prevalent among family members deciding on behalf of ICU patients, rendering them vulnerable. Appropriate measures should be taken to identify and treat them.