Assessment of health-related quality of life as an outcome measure in granulomatosis with polyangiitis (Wegener's)

Objective

To assess a generic measure of health‐related quality of life (HRQOL) as an outcome measure in granulomatosis with polyangiitis (Wegener's) (GPA).

Methods

Subjects were participants in the Wegener's Granulomatosis Etanercept Trial (WGET) or the Vasculitis Clinical Research Consortium Longitudinal Study (VCRC‐LS). HRQOL was assessed with the Short Form 36 (SF‐36) health survey that includes physical and mental component summary scores (PCS and MCS, respectively). Disease activity was assessed with the Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG).

Results

The data from 180 subjects in the WGET (median followup 2.3 years, mean number of visits 10) and 237 subjects in the VCRC‐LS (median followup 2.0 years, mean number of visits 8) were analyzed. A 1 unit increase in the BVAS/WG corresponded to a 1.15 unit (95% confidence interval [95% CI] 1.02, 1.29) decrease for the PCS and a 0.93 (95% CI 0.78, 1.07) decrease for the MCS in the WGET, and to a 1.16 unit decrease for the PCS (95% CI 0.94, 1.39) and a 0.79 unit decrease for the MCS (95% CI 0.51, 1.39) in the VCRC‐LS. In both arms of the WGET study, SF‐36 measures improved rapidly during the first 6 weeks of treatment followed by gradual improvement among patients achieving sustained remission (0.5 improvement in PCS per 3 months), but worsened slightly (0.03 decrease in PCS every 3 months) among patients not achieving sustained remission (P = 0.005).

Conclusion

HRQOL, as measured by the SF‐36, is reduced among patients with GPA. SF‐36 measures are modestly associated with other disease outcomes and discriminate between disease states of importance in GPA.     

Sialylation levels of anti–proteinase 3 antibodies are associated with the activity of granulomatosis with polyangiitis (Wegener's)

Objective

To investigate whether the glycosylation and sialylation levels of anti–proteinase 3 (anti‐PR3) antibodies could affect their pathogenicity, and whether these levels could be correlated with the activity of granulomatosis with polyangiitis (Wegener's) (GPA).

Methods

Forty‐two serum samples positive for anti‐PR3 antibodies from 42 patients with active or weakly active/inactive GPA were included. Anti‐PR3 antibodies were assayed by enzyme‐linked immunosorbent assay, and their levels of glycosylation and sialylation were assessed by enzyme‐linked lectin assay. The glycosylation and sialylation levels of IgG purified from the serum of healthy donors and patients with active, remitted, or weakly active disease were assessed by permethylation and mass spectrometry analysis of glycans, following neuraminidase digestion. The neutrophil oxidative burst induced by purified IgG was assayed by spectrofluorimetry.

Results

The mean sialylation ratio of anti‐PR3 antibodies was significantly lower in patients with active disease than in patients with weakly active or inactive disease, and this was inversely correlated with the Birmingham Vasculitis Activity Score (BVAS) (P < 0.0001). Similar results were obtained using the BVAS/GPA. The area under the receiver operating characteristic curve for the sialylation ratio of anti‐PR3 antibodies, as a test to determine the activity of GPA, was 0.82 (P = 0.0006). The characterization of N‐glycans showed a decrease in 2,6‐linked sialylated N‐glycans and an increase in dHex₁Hex₃HexNAc₄ (mass/charge 1,836) agalactosylated structures in purified IgG from patients with active disease compared with controls. The anti‐PR3 antibody–induced oxidative burst of neutrophils was inversely correlated with the sialylation levels of anti‐PR3 IgG.

Conclusion

The sialylation level of anti‐PR3 antibodies contributes to the clinical activity of GPA, by modulating the oxidative burst of neutrophils induced by these autoantibodies.

     

Hypersomnolence in fibromyalgia syndrome

OBJECTIVE: To evaluate hypersomnolence in patients affected by fibromyalgia syndrome. METHODS: Thirty consecutive patients affected by fibromyalgia syndrome (FMS) (28 F) completed a sleep questionnaire and underwent the following evaluations: lung function tests; polysomnography; the Epworth sleepiness scale (ESS), which measures sleep complaints and daytime hypersomnolence; and the visual analogical scale (VAS) to detect subjective pain, fatigue, anxiety and depression. RESULTS: The FMS patients were divided into two groups based on their ESS score. Patients complaining of daytime hypersomnolence had a higher number of tender points (15 +/- 2 vs. 12 +/- 1, p < 0.01), a higher subjective pain score (72 +/- 15 vs. 52 +/- 13, p < 0.05), and more fatigue (p < 0.05). The diffusing capacity of the lung (Tlco) was more impaired and the occurrence of periodic breathing was higher. FMS patients complaining of daytime somnolence had significantly less efficient sleep than the FMS patients with no daytime somnolence (p < 0.05), i.e. a lower proportion of stage 3 sleep (5 +/- 2% vs. 12 +/- 3%; p < 0.001), stage 4 sleep (1 +/- 0.5% vs. 4 +/- 1%; p < 0.001), and twice as many arousals per hour of sleep (p < 0.01). The respiratory pattern of FMS patients with hypersomnolence showed a higher occurrence of periodic breathing (p < 0.05). The short length of apneas and hypopnoeas did not affect the apnea/hypopnea index (5.1 +/- 3 vs. 7 +/- 4; ns), but FMS patients with daytime hypersomnolence had a greater number of desaturations per hour of sleep (11 +/- 6 vs. 6 +/- 5; p < 0.05). Pulmonary volumes did not differ between the two groups. The EES score was significantly correlated in FMS patients, and even more markedly in the FMS patients with hypersomnolence, TLco, A/I, and disease duration. The ESS score was correlated significantly with the number of tender points only in FMS patients with daytime hypersomnolence. CONCLUSION: The occurrence of daytime hypersomnolence in FMS patients is linked to a greater severity of fibromyalgia symptoms and to more severe polysomnographic alterations.     

Pregabalin for the treatment of fibromyalgia syndrome: Results of a randomized,double‐blind,placebo‐controlled trial

Objective

Fibromyalgia syndrome (FMS) is characterized by widespread musculoskeletal pain and lowered pain threshold. Other prominent symptoms include disordered sleep and fatigue. FMS affects an estimated 2% of the population, predominantly women. This trial was designed to evaluate the efficacy and safety of pregabalin, a novel α₂‐δ ligand, for treatment of symptoms associated with FMS.

Methods

This multicenter, double‐blind, 8‐week, randomized clinical trial compared the effects of placebo with those of 150, 300, and 450 mg/day pregabalin on pain, sleep, fatigue, and health‐related quality of life in 529 patients with FMS. The primary outcome variable was the comparison of end point mean pain scores, derived from daily diary ratings of pain intensity, between each of the pregabalin treatment groups and the placebo group.

Results

Pregabalin at 450 mg/day significantly reduced the average severity of pain in the primary analysis compared with placebo (−0.93 on a 0–10 scale) (P ≤ 0.001), and significantly more patients in this group had ≥50% improvement in pain at the end point (29%, versus 13% in the placebo group; P = 0.003). Pregabalin at 300 and 450 mg/day was associated with significant improvements in sleep quality, fatigue, and global measures of change. Pregabalin at 450 mg/day improved several domains of health‐related quality of life. Dizziness and somnolence were the most frequent adverse events. Rates of discontinuation due to adverse events were similar across all 4 treatment groups.

Conclusion

Pregabalin at 450 mg/day was efficacious for the treatment of FMS, reducing symptoms of pain, disturbed sleep, and fatigue compared with placebo. Pregabalin was well tolerated and improved global measures and health‐related quality of life.

     

Measuring fatigue in rheumatoid arthritis: A cross‐sectional study to evaluate the Bristol Rheumatoid Arthritis Fatigue Multi‐Dimensional questionnaire,visual analog scales,and numerical rating scales

Objective

Current patient‐reported outcome measures of fatigue in rheumatoid arthritis (RA) have limitations, providing only a global perspective. This study constructed a questionnaire (the Bristol RA Fatigue Multi‐Dimensional Questionnaire [BRAF‐MDQ]) from 45 preliminary questions derived from analysis of patient interviews and surveys and explored its structure for fatigue dimensions. The BRAF‐MDQ and short BRAF numerical rating scales (NRS) and visual analog scales (VAS) for severity, effect, and ability to cope with fatigue were evaluated for validity.

Methods

Two hundred twenty‐nine RA patients with fatigue (VAS score ≥5 of 10) completed preliminary BRAF and comparator fatigue scales. Iterative analyses informed item removal or retention in the BRAF‐MDQ and identification of subscales (using Cronbach's alpha for internal consistency and factor analysis to identify dimensions). The BRAF‐MDQ and short scales were tested in relation to potentially associated variables for criterion and construct validity (Spearman's correlation).

Results

The 20‐item BRAF‐MDQ had good internal consistency (Cronbach's α = 0.932), criterion validity (correlation with other fatigue scales: r = 0.643–0.813), and construct validity (correlations with disability, mood, helplessness, and pain: r = 0.340–0.627). Factor analysis showed 4 distinct dimensions (physical fatigue, living with fatigue, cognition fatigue, and emotional fatigue), which correlated well with the RA Multidimensional Assessment of Fatigue scale (r = 0.548–0.834). The BRAF VAS and NRS showed similar criterion and construct validity.

Conclusion

The BRAF instruments include standardized NRS and VAS for fatigue severity, effect, and coping, are RA specific, and have evidence to support validity. The BRAF‐MDQ uniquely measures 4 separate dimensions, which may facilitate development of individually‐tailored fatigue management programs.     

A disease‐specific activity index for Wegener's granulomatosis: Modification of the Birmingham Vasculitis Activity Score

Objective

To refine and validate the Birmingham Vasculitis Activity Score (BVAS) as a disease‐specific activity index for Wegener's granulomatosis (WG).

Methods

Sixteen members of the International Network for the Study of the Systemic Vasculitides (INSSYS) revised the BVAS, with 3 goals: to reduce the redundancy of some component items, to enhance its ability to capture important disease manifestations specific to WG, and to streamline the instrument for use in clinical research. We defined the items and weighted them empirically as either minor (e.g., nasal crusting = 1 point) or major (e.g., alveolar hemorrhage = 3 points). We then validated the new, disease‐specific BVAS/WG in 2 simulation exercises and a clinical case series that involved 117 patients with WG.

Results

We removed 38 items from the original BVAS, revised 9 items, and added 7 new items. Correlations between the scores on the BVAS/WG and the physician's global assessment (PGA) of disease activity were high, even when patients in remission were excluded. In the clinical case series, Spearman's rank correlation coefficient between the BVAS/WG and the PGA was r = 0.81 (95% confidence interval 0.73–0.87). The interobserver reliability using intraclass (within‐case) correlation coefficients in the 2 simulation exercises was r = 0.93 for the BVAS/WG and r = 0.88 for the PGA in the first and r = 0.91 for the BVAS/WG and r = 0.88 for the PGA in the second. There was no significant observer effect in the scoring of the BVAS/WG or the PGA. The discriminant validity of the BVAS/WG was good: r = 0.73 (95% confidence interval 0.43–0.83).

Conclusion

The BVAS/WG is a valid, disease‐specific activity index for WG. Tested in simulation exercises and in actual patients, the BVAS/WG correlates well with the PGA, is sensitive to change, and has good inter‐ and intraobserver reliability. The INSSYS will use the BVAS/WG to assess the primary outcome in a phase II/III trial of etanercept in WG.

     

Revision endoscopic sinus surgery rates by chronic rhinosinusitis subtype

Background

Revision surgery rates following endoscopic sinus surgery (ESS) range between 7% and 50% and are influenced by many factors. This study investigates ESS outcomes for chronic rhinosinusitis (CRS) subtypes.

Methods

Retrospective review of adult CRS patients undergoing ESS with a single surgeon (2010‐2015) was conducted. Outcomes were analyzed by CRS subtypes.

Results

ESS was performed in 424 CRS patients (CRS with nasal polyps [CRSwNP], n = 170; CRS without polyps [CRSsNP], n = 254). Most patients (309; 72.9%) could not be specifically subtyped; 115 (27.1%) were subtyped as follows: aspirin‐exacerbated respiratory disease (AERD), n = 47 (11.1%); allergic fungal sinusitis (AFS), n = 39 (9.2%); immunodeficiency, n = 21 (5.0%); granulomatosis with polyangiitis (GPA), n = 5 (1.2%); and eosinophilic granulomatosis with polyangiitis (EGPA), n = 3 (0.7%). All subgroups experienced clinically meaningful reduction in postoperative 22‐item Sino‐Nasal Outcome Test (SNOT‐22) scores. At median follow‐up of 28 months (interquartile range [IQR], 10–47 months), 19 patients (4%) underwent revision ESS (CRSwNP, n = 6; CRSsNP, n = 13). Revision ESS rates were 3.5% and 5.1% for CRSwNP and CRSsNP, respectively. Revision ESS rate for subtypes were: AERD 2%; AFS 2%; immunodeficiency 14%; GPA 40%; EGPA 0%; and “all other CRS” 4% at median follow‐up duration of 36, 28, 41, 37, 44, and 26 months, respectively.

Conclusion

All CRS subtypes demonstrated clinically meaningful improvement in postoperative SNOT‐22 scores following ESS. Our overall revision ESS rate was 4% (3.5% in CRSwNP). AFS, AERD, and EGPA groups demonstrated low revision rates, while immunodeficiency and GPA patients required more revision surgery. A contemporary understanding of CRSwNP subtypes facilitated surgical and medical strategies in improving outcomes for AERD, AFS, and EGPA patients. CRSsNP subtypes with immunodeficiency and GPA merit further investigation to optimize outcomes.

     

Association between pain, radiographic severity, and centrally-mediated symptoms in women with knee osteoarthritis

Objective

To examine the relationship between pain, radiographic severity, and a common set of co‐occurring centrally‐mediated symptoms (fatigue, sleep quality, and depression) in women with knee osteoarthritis.

Methods

Participants underwent knee radiographs, and had repeated assessments of pain severity and other centrally‐mediated symptoms during a 5‐day home monitoring period. To examine associations between pain severity (the average of pain over the home monitoring period), measures of osteoarthritis radiographic severity (Kellgren/Lawrence grade, minimum joint space width), centrally‐mediated symptoms, and demographics (age) were used. Symptoms of fatigue, sleep efficiency, and depression were used in a composite measure representing centrally‐mediated symptoms.

Results

Using a series of linear regression models in which each variable was entered hierarchically (n = 54), the final model showed that 27% of the variance in pain severity was explained by age, radiographic severity, and centrally‐mediated symptoms. Centrally‐mediated symptoms explained an additional 10% of the variance in pain severity after the other 2 variables were entered.

Conclusion

Both radiographic severity and centrally‐mediated symptoms were independently and significantly associated with pain severity in women with knee osteoarthritis. In addition to more severe radiographic features, women with higher centrally‐mediated symptoms had greater pain severity. Treatments for women with symptomatic knee osteoarthritis may be optimized by addressing both peripheral and central sources of pain.     

Sodium oxybate relieves pain and improves function in fibromyalgia syndrome: A randomized,double‐blind,placebo‐controlled,multicenter clinical trial

Objective

To evaluate the safety and efficacy of sodium oxybate for management of the symptoms of fibromyalgia syndrome (FMS).

Methods

Patients with FMS (according to the American College of Rheumatology 1990 criteria) were randomized, after discontinuing their prestudy medications for FMS, to receive 4.5 gm or 6 gm of sodium oxybate or matching placebo once per night for 8 weeks. The primary outcome variable (POV) was a composite score for changes from baseline in 3 coprimary self‐report measures: patient's pain rating (in daily electronic diaries) on a visual analog scale (PVAS), the Fibromyalgia Impact Questionnaire (FIQ) score, and the Patient Global Impression of Change (PGI‐C). A beneficial response rate for the POV composite score was defined as ≥20% improvement in the PVAS and FIQ scores plus a rating of “much better” or “very much better” on the PGI‐C. Secondary measures included subjective sleep outcomes (on the Jenkins Scale for Sleep) and quality‐of‐life measures. The analyses were based on an intent‐to‐treat (ITT) population.

Results

The ITT population included 188 patients with FMS, 78% of whom completed the trial. Significant benefit was observed with both dosages of sodium oxybate, according to changes in the POV and subjective sleep quality. Improvements in the PVAS score were significantly correlated with sleep outcomes. Sodium oxybate was well tolerated overall; dose‐related nausea (≤28% of patients) and dizziness (≤18% of patients) tended to resolve with continued therapy.

Conclusion

Sodium oxybate therapy was well tolerated and significantly improved the symptoms of FMS. Further study of sodium oxybate as a novel therapeutic option for FMS is warranted.

     

Factors associated with fatigue in early arthritis: Results from a multicenter national French cohort study

Objective

Fatigue frequently occurs in patients with early arthritis (EA). Determinants of its severity are unknown. We aimed to identify the factors associated with fatigue in EA and changes in fatigue after 1 year of followup.

Methods

The Evaluation et Suivi de Polyarthrites Indifférenciées Récentes (Assessment and Followup of Early Undifferentiated Arthritis) cohort study is a multicenter, prospective, national cohort of patients with EA. At baseline and every 6 months up to 1 year, we recorded sociodemographic, clinical, and treatment characteristics, Arthritis Impact Measurement Scales 2 Short Form (AIMS2‐SF) and Short Form 36 (SF‐36) scores for health‐related quality of life (HRQOL), and fatigue severity by a visual analog scale (f‐VAS) and the SF‐36 vitality score (fatigue_SF36).

Results

We included 813 patients (77% women, mean ± SD age 48 ± 13 years). At baseline, fatigue as assessed by the f‐VAS or fatigue_SF36 was independently associated with young age, female sex, low education level, smoking, increased Disease Activity Score in 28 joints (DAS28), waking up at night, Sjögren's syndrome, and worse AIMS2‐SF physical, affect, and symptom scores. At 1‐year followup, a favorable change in fatigue scores was associated with increased baseline AIMS2‐SF physical and affect scores (better quality of life), high baseline fatigue scores, and improved 1‐year AIMS2‐SF affect scores. Age, sex, and change in AIMS2‐SF physical score, DAS28, and hemoglobin or C‐reactive protein level were inconsistently associated with change in fatigue scores. The AIMS2‐SF affect score explained most of the variance in baseline fatigue score and was an important factor in 1‐year change in fatigue score.

Conclusion

Fatigue in EA is multifactorial. Its level and its course are strongly associated with HRQOL, notably the affect dimension. These results should help professionals inform patients about fatigue, explore its causes, and develop tailored interventions.     

Rituximab therapy for systemic vasculitis associated with rheumatoid arthritis: Results from the AutoImmunity and Rituximab Registry

Objective

Rituximab improves articular symptoms in rheumatoid arthritis (RA) and it recently has been shown to be an effective induction therapy for antineutrophil cytoplasmic antibody–associated vasculitis. We assessed the efficacy and safety of rituximab in a real‐life clinical setting among patients with systemic rheumatoid vasculitis (SRV).

Methods

We analyzed data from the AutoImmunity and Rituximab registry, which includes patients with autoimmune diseases treated with rituximab.

Results

Of the 1,994 patients with RA enrolled in the registry, 17 were treated with rituximab for active SRV. At baseline, the mean Birmingham Vasculitis Activity Score for RA (BVAS/RA) was 9.6, with a mean prednisone dosage of 19.2 mg/day. After 6 months of rituximab therapy, 12 patients (71%) achieved complete remission of their vasculitis, 4 had a partial response, and 1 died with uncontrolled vasculitis. Mean BVAS/RA was reduced to 0.6 and mean prednisone dosage to 9.7 mg/day. At 12 months, 14 patients (82%) were in sustained complete remission. Severe infection occurred in 3 patients, corresponding to a 6.4 per 100 patient‐years rate. In the 6 patients who received further rituximab as maintenance therapy between months 6 and 12, no relapse of vasculitis was observed. However, among the 9 patients who did not, a relapse was observed in 3 patients who were treated with methotrexate alone. Remission was reestablished by reintroducing rituximab in 2 cases.

Conclusion

Complete remission of SRV was achieved in nearly three‐fourths of patients receiving rituximab in daily practice, with a significant decrease in daily prednisone dosage and an acceptable toxicity profile. Rituximab represents a suitable therapeutic option to induce remission in SRV, but maintenance therapy seems to be necessary.     

Assessment of sleepiness,fatigue, and depression among Gulf Cooperation Council commercial airline pilots

Purpose

No studies have assessed the prevalence of fatigue, depression, sleepiness, and the risk of obstructive sleep apnea (OSA) among commercial airlines pilots in the Gulf Cooperation Council (GCC).

Methods

This was a quantitative cross­sectional study conducted among pilots who were on active duty and had flown during the past 6 months for one of three commercial airline companies. We included participants with age between 20 and 65 years. Data were collected using a predesigned electronic questionnaire composed of questions related to demographic information in addition to the Fatigue Severity Scale (FSS), the Berlin Questionnaire, the Epworth Sleepiness Scale (ESS), and the Hospital Anxiety and Depression Scale (HADS).

Results

The study included 328 pilots with a mean age ± standard deviation of 41.4 ± 9.7 years. Overall, 224 (68.3%) pilots had an FSS score ≥ 36 indicating severe fatigue and 221 (67.4%) reported making mistakes in the cockpit because of fatigue. One hundred and twelve (34.1%) pilots had an ESS score ≥ 10 indicating excessive daytime sleepiness and 148 (45.1%) reported falling asleep at the controls at least once without previously agreeing with their colleagues. One hundred and thirteen (34.5%) pilots had an abnormal HADS depression score (≥ 8), and 96 (29.3%) pilots were at high risk for OSA requiring further assessment.

Conclusion

Fatigue, sleepiness, risk of OSA, and depression are prevalent among GCC commercial airline pilots. Regular assessment by aviation authorities is needed to detect and treat these medical problems.

     

Efficacy of multicomponent treatment in fibromyalgia syndrome: A meta‐analysis of randomized controlled clinical trials

Objective

To systematically review the efficacy of multicomponent treatment of fibromyalgia syndrome (FMS).

Methods

We screened Medline, PsychINFO, Scopus, and the Cochrane Library (through December 2007), as well as reference sections of original studies, reviews, and evidence‐based guidelines. Randomized controlled trials (RCTs) on the multicomponent treatment (at least 1 educational or other psychological therapy with at least 1 exercise therapy) of FMS were analyzed.

Results

We included 9 (of 14) RCTs with 1,119 subjects (median treatment time 24 hours) in the meta‐analysis. Effects were summarized using standardized mean differences (SMDs) or weighted mean differences (WMDs). There was strong evidence that multicomponent treatment reduces pain (SMD ?0.37; 95% confidence interval [95% CI] ?0.62, ?0.13), fatigue (WMD ?0.85; 95% CI ?1.50, ?0.20), depressive symptoms (SMD ?0.67; 95% CI ?1.08, ?0.26), and limitations to health‐related quality of life (HRQOL) (SMD ?0.59; 95% CI ?0.90, ?0.27) and improves self‐efficacy pain (SMD 0.54; 95% CI 0.26, 0.82) and physical fitness (SMD 0.30; 95% CI 0.02, 0.57) at posttreatment. There was no evidence of its efficacy on pain, fatigue, sleep disturbances, depressive symptoms, HRQOL, or self‐efficacy pain in the long term. There was strong evidence that positive effects on physical fitness (SMD 0.30; 95% CI 0.09, 0.51) can be maintained in the long term (median followup 7 months).

Conclusions

There is strong evidence that multicomponent treatment has beneficial short‐term effects on the key symptoms of FMS. Strategies to maintain the benefits of multicomponent treatment in the long term need to be developed.

     

Improvement in health-related quality of life in MPO-ANCA-associated vasculitis patients treated with cyclophosphamide plus prednisolone: an analysis of 18 months of follow-up data from the JMAAV study

Objectives

To examine the improvement in health-related quality of life (HRQOL) in association with disease activity in myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis patients treated with cyclophosphamide plus prednisolone.

Methods

According to the Japanese Patients with MPO-ANCA-Associated Vasculitis (JMAAV) study protocol, a total of 48 patients with newly diagnosed MPO-ANCA-associated vasculitis received a standardized cyclophosphamide plus prednisolone regimen, and their clinical courses were followed for 18?months following their entry into the study. Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS) 2003. HRQOL was assessed using MOS Short-Form 36 (SF-36) v2. BVAS new/worse, BVAS persistent, and SF-36 domain scores (norm-based) were calculated for the 32 eligible patients.

Results

The mean SF-36 domain scores were significantly lower than the Japanese general population norm. Stepwise multiple linear regression analysis showed that the presence of new or worsening features of the nervous system was significantly associated with a deterioration in physical function. During the 18?months of follow-up, there were significant improvements in BVAS new/worse and all SF-36 domains except for general health and role emotional.

Conclusion

MPO-ANCA-associated vasculitis patients experienced a considerable deterioration in HRQOL. The standardized cyclophosphamide plus prednisolone regimen of the JMAAV study induced remission in the majority of patients, and the induction of remission accompanied a recovery in HRQOL.     

Factors associated with excessive daytime sleepiness in patients with severe obstructive sleep apnea

Purpose

Although excessive daytime sleepiness (EDS) is one of the key symptoms of obstructive sleep apnea (OSA), associations between OSA and EDS have been inconsistent, even in patients with severe OSA. To that end, our goal was to investigate factors associated with EDS based on the Epworth Sleepiness Scale (ESS) score in a large clinical population with severe OSA (apnea–hypopnea index ≥30).

Methods

This cross-sectional study included 1,126 consecutive adult patients referred for their first in-laboratory polysomnogram for suspicion of OSA. All patients completed a routine questionnaire including demographics, race, co-morbidities, sleep history, ESS, short-form quality of life questionnaire-12 (SF-12), the Center for Epidemiologic Studies Depression scale, and medications used. Severe OSA was diagnosed in 498 patients. After excluding patients taking narcotics, hypnotics, benzodiazepines, antidepressants, or those with diagnosis of depression, 355 patients remained in the final analytic cohort. Patients were divided into quartiles based on the ESS and comparisons were made between the lowest quartile (ESS?≤?6; n?=?105) and highest quartile (ESS?≥?13; n?=?97).

Results

Compared to the ESS?≤?6 group, patients in the ESS?≥?13 group had a significantly higher 3 % oxygen desaturation index and a significantly lower oxygen saturation nadir during sleep (p?<?0.05). Moreover, patients with severe OSA in the highest quartile of ESS had higher depressive symptomatology.

Conclusions

In patients with severe OSA, intermittent hypoxemia and depressive symptoms are important contributing factors to EDS.     

The distribution and outcome of vasculitic syndromes among Egyptians: A multi-centre study including 630 patients

Aim of the work.

Studies describing the epidemiology of vasculitis in the Middle East and Africa are limited. The aim of this multi-centre study is to describe the distribution and outcome of vasculitic syndromes among Egyptian vasculitis patients seen by rheumatologists.

Etanercept combined with conventional treatment in Wegener's granulomatosis: A six‐month open‐label trial to evaluate safety

Objective

To evaluate the safety of etanercept (Enbrel) in patients receiving conventional treatment for Wegener's granulomatosis (WG).

Methods

We performed a 6‐month open‐label trial of etanercept (25 mg subcutaneously twice weekly) which was added to standard therapies for WG (glucocorticoids, methotrexate, cyclophosphamide, azathioprine, cyclosporine) and prescribed according to disease severity. Evaluations of clinical response were determined by the Birmingham Vasculitis Activity Score for WG (BVAS/WG) in 20 patients with persistently active disease or with new flares of previously established WG. Fourteen of the 20 patients (70%) had etanercept added as the only new therapeutic variable.

Results

Injection site reactions (ISRs) were the most common adverse event related to etanercept (8 episodes in 5 patients [25%]; <1% of all injections). All ISRs were mild. Two patients had a combined total of 5 hospitalizations (1 patient had 4), but no hospitalizations were attributable solely to etanercept‐related adverse events. One patient with severe subglottic stenosis developed pneumococcal tracheobronchitis and subsequently had a localized Herpes zoster infection. Nineteen patients (95%) were still taking etanercept at 6 months, the single exception being a patient who developed progression of orbital (retro‐bulbar) disease at 4 months. There were no deaths. The mean BVAS/WG at entry was 3.6 (range 1–8), which decreased at 6 months to 0.6 (P < 0.001, 95% confidence interval [95% CI] −4.0 to −2.1). Among the 14 patients in whom etanercept was the only new treatment variable, the mean daily prednisone dose decreased from 12.9 mg at entry to 6.4 mg at 6 months. This comparison did not achieve statistical significance (difference −6.5; P = 0.19, 95% CI −16.6 to +3.6). Sixteen of the patients (80%) achieved BVAS/WG scores of 0 at some point. However, intermittently active disease was observed in 15 patients (75%).

Conclusion

In this open‐label trial, etanercept used in combination with standard treatments was well‐tolerated in patients with WG. Adverse events were few. BVAS/WG scores improved at 6 months, but intermittently active WG (occasionally severe) was common. A randomized, double‐masked trial to assess the efficacy of etanercept in WG has begun.

     

Cognitive behavioral therapy for the treatment of juvenile fibromyalgia: A multisite,single‐blind,randomized, controlled clinical trial

Objective

Juvenile fibromyalgia syndrome (FMS) is a chronic musculoskeletal pain disorder in children and adolescents for which there are no evidence‐based treatments. The objective of this multisite, single‐blind, randomized clinical trial was to test whether cognitive–behavioral therapy (CBT) was superior to fibromyalgia (FM) education in reducing functional disability, pain, and symptoms of depression in juvenile FMS.

Methods

Participants were 114 adolescents (ages 11–18 years) with juvenile FMS. After receiving stable medications for 8 weeks, patients were randomized to either CBT or FM education and received 8 weekly individual sessions with a therapist and 2 booster sessions. Assessments were conducted at baseline, immediately following the 8‐week treatment phase, and at 6‐month followup.

Results

The majority of patients (87.7%) completed the trial per protocol. Intent‐to‐treat analyses showed that patients in both groups had significant reductions in functional disability, pain, and symptoms of depression at the end of the study, and CBT was significantly superior to FM education in reducing the primary outcome of functional disability (mean baseline to end‐of‐treatment difference between groups 5.39 [95% confidence interval 1.57, 9.22]). Reduction in symptoms of depression was clinically significant for both groups, with mean scores in the range of normal/nondepressed by the end of the study. Reduction in pain was not clinically significant for either group (<30% decrease in pain). There were no study‐related adverse events.

Conclusion

In this controlled trial, CBT was found to be a safe and effective treatment for reducing functional disability and symptoms of depression in adolescents with juvenile FMS.

     

Liver involvement in ANCA-associated vasculitis

The aim of the study was to investigate the incidence, the clinical course and outcome of liver involvement and autoimmune hepatic diseases in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Liver function tests (LFT) (i.e. aspartate and alanine aminotransferase [AST, ALT], gamma-glutamyl transpeptidase [gamma-GT], alkaline phosphatase [ALP] and total bilirubin) were analysed at disease onset in therapy-naïve patients and during remission in patients with granulomatosis with polyangiitis (GPA, n?=?67), microscopic polyangiitis (MPA, n?=?28) and eosinophilic granulomatosis with polyangiitis (EGPA, n?=?14). Results were correlated to the Birmingham Vasculitis Activity Score version 3 (BVAS v.3). Also, serologic tests for other autoimmune hepatic diseases were performed in these patients. During the active state, LFT abnormalities could be detected in 54 AAV patients (49.4 %). ALT, gamma-GT and ALP were significantly higher in GPA patients compared to MPA or EGPA patients at disease onset (p?<?0.05). Increased values for gamma-GT in GPA patients correlated with the BVAS (p?<?0.01) and were associated with pulmonary involvement, pulmonary-renal syndrome and a longer time to remission. Increased LFT in GPA patients decreased subsequently towards normal levels after initiation of therapy (p?<?0.01). No case of severe liver involvement or autoimmune hepatic liver diseases was found in AAV patients. Liver involvement was mainly restricted to GPA patients, is associated with the disease activity and indicates a poorer outcome in patients with GPA. Progressive liver involvement or autoimmune hepatic diseases were not observed.     

Circulating markers of vascular injury and angiogenesis in antineutrophil cytoplasmic antibody–associated vasculitis

Objective

To identify biomarkers that distinguish between active antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) and remission in a manner superior or complementary to established markers of systemic inflammation.

Methods

Markers of vascular injury and angiogenesis were measured before and after treatment in a large clinical trial in AAV: 163 subjects enrolled in the Rituximab in ANCA‐Associated Vasculitis trial were screened for the present study. Serum levels of E‐selectin, intercellular adhesion molecule 3 matrix metalloproteinase protein 1 (MMP‐1), MMP‐3, MMP‐9, P‐selectin, thrombomodulin, and vascular endothelial growth factor were measured at study screening (time of active disease) and at month 6. Erythrocyte sedimentation rate (ESR) and C‐reactive protein (CRP) levels had been measured at the time of the clinical visit. The primary outcome measure was the difference in marker level between screening and month 6 among patients whose disease was in remission (Birmingham Vasculitis Activity Score for Wegener's granulomatosis [BVAS/WG] score of 0) at month 6.

Results

All patients had severe active vasculitis at screening (mean ± SD BVAS/WG score 8.6 ± 3.2). Among the 123 patients whose disease was clinically in remission at month 6, levels of all markers except E‐selectin showed significant declines. MMP‐3 levels were also higher among the 23 patients with active disease at month 6 than among the 123 patients whose disease was in remission. MMP‐3 levels correlated weakly with ESR and CRP levels.

Conclusion

Many markers of vascular injury and angiogenesis are elevated in severe active AAV and decline with treatment, but MMP‐3 appears to distinguish active AAV from remission better than the other markers studied. Further study of MMP‐3 is warranted to determine its clinical utility in combination with conventional markers of inflammation and ANCA titers.