ObjectivesPrior 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.Methods16S 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.ResultsCompared 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.ConclusionsGPA 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.

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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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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 PARTICIPANTSThe 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 MEASURESThe 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.