Does oral appliance efficacy in treating obstructive sleep apnea depend on the appliance specialist's experience?

PURPOSE: In France, oral appliances (OAs) are the first-line treatment for moderate and second-line treatment for severe obstructive sleep apnea-hypopnea syndrome. In general, the sleep specialist refers his/her patient to the appliance specialist for the impressions and the fitting. However, is there a relationship between the volume of activity of the appliance specialist and the efficacy of this device? METHODS: Our unit includes seven appliance otolaryngology specialists whose activities are highly variable (number of patients varying by a factor of almost 10). Data from a prospective follow-up registry of patients treated with an OA for moderate and severe obstructive sleep apnea-hypopnea syndrome were studied, and differences in outcomes between practitioners in the team were sought. RESULTS: Among 859 patients, OAs significantly reduced the apnea-hypopnea index. Even if the patients were not completely comparable from one practitioner to another, there was a significant heterogeneity in efficacy (complete or partial response of the apnea-hypopnea index and failure of OAs) between practitioners (p = 0.0038; 0.0011; 0.0007 respectively), with better results in practitioners with a higher level of OA activity. CONCLUSION: The findings suggest that it may be preferable to refer patients to OA practitioners who see a higher volume of patients with moderate or severe obstructive sleep apnea-hypopnea syndrome treated with an OA.

Elevated BLyS levels in patients with systemic lupus erythematosus: Associated factors and responses to belimumab.

INTRODUCTION: Patients with systemic lupus erythematosus (SLE) with B-lymphocyte stimulator (BLyS) levels ≥ 2 ng/mL are at increased risk of flare. A regression analysis was undertaken to identify routine clinical measures that correlate with BLyS ≥ 2 ng/mL. Efficacy and safety of belimumab 10 mg/kg were examined in patients with BLyS ≥ 2 ng/mL and < 2 ng/mL. METHODS: Data from BLISS-52 and -76 (N = 1684) were pooled post hoc. A univariate logistic regression was employed to identify factors predictive of baseline BLyS ≥ 2 ng/mL. Factors significant at the 0.05 level then entered a stepwise logistic regression as covariates. Efficacy endpoints included SLE responder index (SRI), ≥ 4-point reduction in Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and risk of severe flare over 52 weeks. Adverse events (AEs) were analyzed for each treatment arm and BLyS subgroup. RESULTS: Baseline predictors of BLyS ≥ 2 ng/mL included positive anti-Smith (≥ 15 U/mL), low complement (C) 3 (< 900 mg/L), anti-double-stranded DNA (anti-dsDNA) 80-200 and ≥ 200 IU/mL, immunosuppressant usage, proteinuria, elevated C-reactive protein (CRP), and low total lymphocyte count for all patients. Belimumab 10 mg/kg led to significantly greater SRI responses over 52 weeks versus placebo in both BLyS subgroups, though treatment differences were numerically greater at Week 52 in the BLyS ≥ 2 ng/mL group (24.1%, p < 0.0001) compared with BLyS < 2 ng/mL (8.2%, p = 0.0158). Results were similar for ≥ 4-point reduction in SELENA-SLEDAI. Risk of severe flare over 52 weeks was significantly reduced with belimumab 10 mg/kg versus placebo in the BLyS ≥ 2 ng/mL group (p = 0.0002). AEs were similar across treatment arms and BLyS subgroups. CONCLUSIONS: Positive anti-Smith, low C3, anti-dsDNA ≥ 80 IU/mL, immunosuppressant usage, proteinuria, elevated CRP, and low total lymphocyte count were predictors of BLyS ≥ 2 ng/mL. Monitoring these factors could identify patients with BLyS ≥ 2 ng/mL who are at risk of flare.

Self-reported health outcomes in patients with psoriasis and psoriatic arthritis randomized to two etanercept regimens.

BACKGROUND: Moderate/severe psoriasis combined with psoriatic arthritis (PsA) impairs health-related quality of life (QoL). Etanercept, a fully human tumour necrosis factor-α receptor fusion protein, is approved for treatment of both diseases. OBJECTIVE: To compare patient-reported health outcomes (PROs) of two etanercept regimens in patients with moderate/severe psoriasis and PsA. METHODS: In this randomized, double-blind, multicenter study, participants received etanercept 50 mg twice weekly (BIW; n = 379) or 50 mg weekly (QW; n = 373) for 12 weeks and open-label etanercept 50 mg QW for 12 additional weeks. PROs included: the EuroQOL-5D (EQ-5D), which measures general health status and consists of the utility index measuring five dimensions of health, and a visual analogue scale (VAS) allowing patients to assess health status; the Dermatology Life Quality Index (DLQI), which measures the impact of skin disease on QoL; the Health Assessment Questionnaire-Disability Index (HAQ-DI), an assessment of physical function; the Hospital Anxiety and Depression Scale (HADS), which screens for anxiety and depression symptoms; and individual questions on general health, disease activity, fatigue, itching, joint pain and morning stiffness. RESULTS: At baseline, patients reported QoL worse than that seen in many chronic medical conditions. Significant within-group improvements in each PRO occurred from baseline to Week 12 (P < 0.001) in both groups and were maintained at Week 24; DLQI, EQ-5D, HAQ-DI and self assessments improved significantly (P < 0.001) from baseline as early as Week 3. At Week 12, but not Week 24, improvement in DLQI, itching and psoriasis activity was greater in the BIW arm (P ≤ 0.004). Improvements in other PROs were always similar between groups. CONCLUSIONS: Greater improvements in PROs specific to skin disorders were seen with etanercept BIW than QW at Week 12, but not at Week 24. Both etanercept regimens led to sustained PRO improvements, starting as early as Week 3.

Combination of skin, joint and quality of life outcomes with etanercept in psoriasis and psoriatic arthritis in the PRESTA trial.

BACKGROUND: Psoriasis and psoriatic arthritis (PsA) affect skin, and/or joints and quality of life (QoL). OBJECTIVE: To better assess the success in multiple attributes in subjects with both active psoriasis and PsA, the objective was to quantify the proportion of those who achieved substantial improvement in a composite measure of skin symptoms, joint manifestations, and QoL, on one of two treatment regimens. METHODS: Subjects (n=752) with psoriasis and PsA (mean age: 46.5 years, 62.9% male) received etanercept (ETN) 50mg twice weekly (BIW; n = 379) or 50 mg weekly (QW; n=373) for 12 weeks, followed by open-label ETN 50mg QW for 12 weeks. Skin and joint symptoms and QoL were assessed using psoriasis area and severity index (PASI), American College of Rheumatology criteria (ACR) and Euro-QoL (EQ-5D), respectively. RESULTS: By week 24, 30.6% and 25.8% of subjects receiving ETN 50 mg BIW/QW and ETN 50 mg QW/QW, respectively (P = 0.198) achieved the composite measure of efficacy for skin plus joints plus QoL (PASI 75 + ACR 50 + EQ-5D VAS >82). CONCLUSION: At 24 weeks, 25.8-30.6% met the triad of rigorous efficacy outcomes. Evaluation of treatment efficacy should address the multiple components of this disease complex; therefore it may be important to consider this composite measure in future trials.

Improvements in patient-reported outcomes in moderate-to-severe psoriasis patients receiving continuous or paused etanercept treatment over 54 weeks: the CRYSTEL study.

OBJECTIVE: To assess patient-reported outcomes (PRO) in patients with moderate-to-severe plaque psoriasis receiving continuous or paused etanercept treatment. METHODS: In a multicentre European open-label study, one group (n = 352) received continuous therapy: 25 mg subcutaneously (SC) twice weekly (BIW) throughout 54-weeks. The other group (n = 359) received paused therapy: 50 mg SC BIW (

Sustained improvement in joint pain and nail symptoms with etanercept therapy in patients with moderate-to-severe psoriasis.

BACKGROUND: To determine the prevalence of joint and nail symptoms, impact of these symptoms on health-related quality of life (HR-QoL), and the effects of etanercept on them in patients with moderate-to-severe plaque psoriasis. METHODS: In CRYSTEL, patients with psoriasis received etanercept continuously (n = 357) or as paused therapy (n = 363) for 54 weeks. In post hoc analyses, baseline characteristics and after-treatment changes were evaluated in patients with baseline joint pain or nail psoriasis, pooling across treatment groups. Assessments of symptom severity and HR-QoL included the Subject Global Assessment question on joint pain, NAPSI, DLQI and EQ-5D. RESULTS: Of 711 patients, 64% reported joint pain and 79% nail psoriasis at baseline. Patients with baseline joint pain or nail psoriasis had significantly worse HR-QoL than unaffected patients. Mean baseline differences between patients with and without joint pain in DLQI (3.3), EQ-5D utility (0.2), and EQ-5D VAS (7.3) were clinically meaningful. In patients with nail psoriasis, a clinically meaningful difference in EQ-5D VAS (5.0) was seen. Etanercept significantly improved symptom severity and HR-QoL. Patients with joint pain had improvements of 47%, 61%, 29%, and 23% in mean joint pain score, DLQI, EQ-5D utility, and EQ-5D VAS, respectively, at Week 54. Patients with nail psoriasis had improvements of 51%, 63%, and 24% in NAPSI, DLQI, and EQ-5D VAS. CONCLUSION: In this study of moderate-to-severe plaque psoriasis, joint and nail symptoms were prevalent and patients with these symptoms had significantly greater HR-QoL impairment at baseline than unaffected patients. Etanercept provided significant improvement in symptom severity and HR-QoL.

Familial occurrence of systemic sclerosis, rheumatoid arthritis and other immunological disorders: report of two kindreds with study of HLA antigens and review of the literature.

We report two Caucasian families with systemic sclerosis and other connective tissue and immunological disorders, including rheumatoid arthritis, discoid lupus erythematosus, psoriasis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, asthma, Sjögren's syndrome, Raynaud's phenomenon and thyroid disease. In one of these families, two sisters are affected with systemic sclerosis. Clinical, serological, and HLA haplotype results are reported, along with a review of the medical literature on familial occurrence of systemic sclerosis.