Efficacy Of Baricitinib in Patients With Moderate-To-Severe Rheumatoid Arthritis Up to 6.5 Years Of Treatment: Results Of A Long-Term Study.

OBJECTIVES: To evaluate the long-term efficacy of once-daily baricitinib 4 mg or 2 mg in patients with active rheumatoid arthritis who had inadequate response (IR) to MTX, csDMARDs, or bDMARDs. METHODS: Data from three completed phase III studies, RA-BEAM (MTX-IR), RA-BUILD (csDMARD-IR), and RA-BEACON (bDMARD-IR), and one completed long-term extension study (RA-BEYOND) were analyzed up to 6.5 years (340 weeks [RA-BEAM] and 336 weeks [RA-BUILD and RA-BEACON]). Low disease activity (LDA) (Simplified Disease Activity Index [SDAI] ≤11), clinical remission (SDAI ≤3.3), and physical function (Health Assessment Questionnaire Disability Index [HAQ-DI] ≤0.5) were the main outcomes assessed. Completer and non-responder imputation (NRI) analyses were conducted on each population. RESULTS: At week 340 or 336, LDA was achieved in 37%/83% of MTX-IR, 35%/83% of csDMARD-IR, and 23%/73% of bDMARD-IR patients treated with baricitinib 4 mg, assessed by NRI/completer analyses, respectively. Remission was achieved in 20%/40% of MTX-IR, 13%/32% of csDMARD-IR, and 9%/30% of bDMARD-IR patients treated with baricitinib 4 mg, assessed by NRI/completer analyses, respectively. HAQ-DI ≤0.5 was reached in 31%/51% of MTX-IR, 25%/46% of csDMARD-IR, and 24%/38% of bDMARD-IR patients treated with baricitinib 4 mg, assessed by NRI/completer analyses, respectively. CONCLUSION: Treatment with baricitinib 4 mg or 2 mg demonstrated efficacy up to 6.5 years with maintained LDA/remission results across SDAI, CDAI and DAS28-hsCRP consistent with previously reported data, and was well tolerated.

Polypharmacy and Drug Interactions in the COVID-19 Pandemic.

The COVID-19 pandemic generated a great impact on health systems. We compared evolution, polypharmacy, and potential drug-drug interactions (P-DDIs) in COVID-19 and non-COVID-19 hospitalizations during first wave of pandemic. Prescriptions for hospitalized patients ≥ 18 years (COVID-19 and non-COVID-19 rooms) between April and September 2020 were included. The computerized medical decision support system SIMDA and the physician order entry system Hdc.DrApp.la were used. Patients in COVID-19 rooms were divided into detectable and non-detectable, according to real-time reverse transcription polymerase chain reaction (RT-PCR). Number of drugs, prescribed on day 1, after day 1, and total; polypharmacy, excessive polypharmacy, and P-DDIs were compared. 1,623 admissions were evaluated: 881 COVID-19, 538 detectable and 343 non-detectable, and 742 non-COVID-19. Mortality was 15% in COVID-19 and 13% in non-COVID-19 (RR [non-COVID-19 vs. COVID-19]: 0.84 [95% CI] [0.66-1.07]). In COVID-19, mortality was 19% in detectable and 9% in non-detectable (RR: 2.07 [1.42-3.00]). Average number of drugs was 4.54/patient (SD ± 3.06) in COVID-19 and 5.92/patient (±3.24) in non-COVID-19 (p<0.001) on day 1 and 5.57/patient (±3.93) in COVID-19 and 9.17/patient (±5.27) in non-COVID-19 (p<0.001) throughout the hospitalization. 45% received polypharmacy in COVID-19 and 62% in non-COVID-19 (RR: 1.38 [1.25-1.51]) and excessive polypharmacy 7% in COVID-19 and 14% in non-COVID-19 (RR: 2.09 [1.54-2.83]). The frequency of total P-DDIs was 0.31/patient (±0.67) in COVID-19 and 0.40/patient (±0.94) in non-COVID-19 (p=0.022). Hospitalizations in the COVID-19 setting are associated with less use of drugs, less polypharmacy and less P-DDIs. Detectable patients had higher mortality.

Cardiovascular events and risk in patients with systemic lupus erythematosus: Systematic literature review and meta-analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease that typically affects women aged 16-55 years. Cardiovascular disease (CVD) is a well-recognized complication of SLE. This systematic literature review and meta-analysis evaluated the relative risk (RR; compared with non-SLE controls), absolute risk (AR; as incidence proportion, n/N), and incidence rate (IR) of CVD events (including stroke, myocardial infarction [MI], and CVD [composite or undefined]) in adult patients with SLE. The RR of CV risk factors (including hypertension, diabetes, and metabolic syndrome [MetS]) was also examined. METHODS: PubMed and Embase were searched on September 10, 2020. Observational studies published between January 2010 and September 2020 that reported RR, AR, and/or IR of CVD events, or RR of CV risk factors, were eligible. Pooled risk estimates were calculated using a random-effects model. RESULTS: Forty-six studies (16 cross-sectional, 15 retrospective cohort, 14 prospective cohort, and 1 case-control) were included in meta-analyses. Most studies were considered high quality (Critical Appraisal Skills Programme checklists). Compared with adults without SLE, patients with SLE had statistically significantly higher RRs (95% CIs) of stroke (2.51 [2.03-3.10]; 12 studies), MI (2.92 [2.45-3.48]; 11 studies), CVD (2.24 [1.94-2.59]; 8 studies), and hypertension (2.70 [1.48-4.92]; 7 studies). RRs of diabetes (1.24 [0.78-1.96]; 3 studies) and MetS (1.49 [0.95-2.33]; 7 studies) were elevated but not significant. RRs of stroke and MI were generally higher in younger versus older patients with SLE. In patients with SLE, the pooled estimate of AR (95% CI) was 0.03 (0.02-0.05), 0.01 (0.00-0.02), and 0.06 (0.03-0.10) for stroke (7 studies), MI (6 studies), and CVD (8 studies), respectively. The pooled estimate of IR per 1000 person-years (95% CI) was 4.72 (3.35-6.32), 2.81 (1.61-4.32), and 11.21 (8.48-14.32) for stroke (10 studies), MI (6 studies), and CVD (8 studies), respectively. Although heterogeneity (based on I2 value) was high in most analyses, sensitivity analyses confirmed the robustness of the pooled estimates. CONCLUSIONS: This meta-analysis found an increased risk of stroke, MI, CVD, and hypertension in patients with SLE compared with the general population, despite substantial heterogeneity across the included studies.

Resistance to Prostaglandin E2 Promotes Monocyte Activation During Chronic HIV Infection.

BACKGROUND: Monocyte activation is a driver of inflammation in the course of chronic HIV infection. Prostaglandin E2 (PGE2) is known to mediate anti-inflammatory effects, notably the inhibition of tumor necrosis factor- (TNF-) production by monocytes. We aim to investigate the effects of PGE2 on activation of monocytes in chronic HIV infection and the mechanisms through which PGE2 modulates their inflammatory signature. METHODS: We recruited a group of people with HIV (PWH) and matched healthy uninfected persons. We compared plasma levels of PGE2, monocyte activation, and sensitivity of monocytes to the inhibitory actions mediated by PGE2. RESULTS: We found increased plasma levels of PGE2 in PWH, and an activated phenotype in circulating monocytes, compared with uninfected individuals. Monocytes from PWH showed a significant resistance to the inhibitory actions mediated by PGE2; the concentration of PGE2 able to inhibit 50 of the production of TNF- by lipopolysaccharide-stimulated monocytes was 10 times higher in PWH compared with uninfected controls. Furthermore, the expression of phosphodiesterase 4B, a negative regulator of PGE2 activity, was significantly increased in monocytes from PWH. CONCLUSIONS: Resistance to the inhibitory actions mediated by PGE2 could account, at least in part, for the inflammatory profile of circulating monocytes in PWH.

Systematic Literature Review and Meta-analysis of Venous Thromboembolism Events in Systemic Lupus Erythematosus.

The objective of this work was to conduct a systematic literature review (SLR) and meta-analysis (MA) to evaluate the relative risk (RR) of venous thromboembolism (VTE) events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients with systemic lupus erythematosus (SLE) compared with patients without SLE, as well as the absolute risk (AR) (measured by incidence proportion) and incidence rate (IR) of VTE events in patients with SLE. The SLR was conducted using Embase, MEDLINE, and MEDLINE In-Process to identify observational studies evaluating the risk of VTE, DVT, and PE events in adult patients with SLE compared with the general population, published January 2000 to September 2020. Random-effects models were used as the primary approach in the MA. Heterogeneity was assessed on the basis of the I2 value. Sensitivity analyses were performed to assess the robustness of results to various conditions, and subgroup analysis was performed for the AR of VTE by antiphospholipid status (aPLs) and antiphospholipid syndrome (APS). Of the 50 publications included for data extraction, 44 contained data for consideration in the MA of any one of the measures of interest (RR, AR, or IR) for VTE, DVT, or PE. The pooled RR indicates statistically significantly higher risk of VTE (RR 4.38, 95% confidence interval 2.63-7.29) in patients with SLE compared with the general population. Considerable heterogeneity was present in nearly all MA (I2 = 75-100%). Moreover, a higher pooled AR of VTE was estimated in patients with SLE with aPLs (n/N = 0.13) and APS (n/N = 0.63) compared with patients with SLE without aPLs/APS (n/N = 0.07). Overall, there was evidence of an increased risk of VTE, DVT, and PE in patients with SLE compared with the general population.

Treatment Patterns and Clinical Characteristics of Patients with Systemic Lupus Erythematosus and Musculoskeletal Symptoms: A Retrospective, Observational Study.

INTRODUCTION: Musculoskeletal (MSK) symptoms, including arthritis and arthralgia, are common manifestations of systemic lupus erythematosus (SLE); definitions of activity patterns in SLE differ across studies. This study described clinical characteristics and treatment patterns of patients with SLE-MSK over time and by disease activity patterns from a real-world setting. METHODS: This retrospective descriptive analysis includes a subset of patients with SLE from the Hopkins Lupus Cohort with identified MSK involvement by scores on the arthritis domain of the Safety of Estrogens in Systemic Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) or Lupus Activity Index. Clinical characteristics and treatment patterns were described for patients with at least two visits over the observation period (2010-2019) for the SLE-MSK population based on three disease activity patterns: chronically active (MSK-CA), relapsing-remitting (MSK-RR), and long quiescence (MSK-LQ). RESULTS: The SLE-MSK subpopulation included 664 patients (4069 person-years). The most frequently used medications over the observation period were antimalarials (95%), corticosteroids (92%), immunosuppressants (58%), and nonsteroidal anti-inflammatory drugs (NSAIDs) (48%); 7% of patients used biologics. The highest use of corticosteroids was in the MSK-CA group (90.5% of follow-up time), followed by MSK- RR (83.9%), and MSK-LQ (46.5%). Mean prednisone dose was significantly higher in MSK-RR (8.5 mg) compared to MSK-CA (6.5 mg). CONCLUSIONS: This descriptive analysis highlights the impact of prevalent manifestations such as arthritis on the chronic use of corticosteroids, immunosuppressants, and NSAIDs to manage disease activity in patients with SLE, suggesting there is a need for new therapeutic options that enable a lower use of medication when treating lupus.

A Narrative Literature Review Comparing the Key Features of Musculoskeletal Involvement in Rheumatoid Arthritis and Systemic Lupus Erythematosus.

Although the clinical approach to the management of musculoskeletal manifestations in systemic lupus erythematosus (SLE) is often similar to that of rheumatoid arthritis (RA), there are distinct differences in immunopathogenesis, structural and imaging phenotypes and therapeutic evidence. Additionally, there are few published comparisons of these diseases. The objective of this narrative literature review is to compare the immunopathogenesis, structural features, magnetic resonance imaging (MRI) and musculoskeletal ultrasound (MSUS) studies and management of joint manifestations in RA and SLE. We highlight the key similarities and differences between the two diseases. Overall, the literature evaluated indicates that synovitis and radiographical progression are the key features in RA, while inflammation without swelling, tendinitis and tenosynovitis are more prominent features in SLE. In addition, the importance of defining patients with RA by the presence or absence of autoantibodies and categorizing patients with SLE by synovitis detected by musculoskeletal ultrasound and by structural phenotype (non-deforming, non-erosive arthritis, Jaccoud's arthropathy and 'Rhupus') with respect to joint manifestations will also be discussed. An increased understanding of the joint manifestations in RA and SLE may inform evidence-based clinical decisions for both diseases.

Achieving pain control in early rheumatoid arthritis with baricitinib monotherapy or in combination with methotrexate versus methotrexate monotherapy.

OBJECTIVES: This post hoc analysis assessed speed, magnitude and maintenance of pain improvement in patients with early rheumatoid arthritis (RA) receiving baricitinib, baricitinib and methotrexate (MTX), or MTX over 1 year. Cumulative pain and quality of life benefits were also assessed. METHODS: Randomised, double-blind, phase 3 study RA-BEGIN (NCT01711359) compared baricitinib 4 mg (N=159), baricitinib 4 mg +MTX (N=215) and MTX (N=210) in patients with RA who had no or limited prior disease-modifying antirheumatic drug treatment. Pain was assessed on a 0-100 mm Visual Analogue Scale (VAS). Proportion of patients with ≥30%, ≥50% and ≥70% pain improvement from baseline; ≤20 mm and ≤10 mm on the pain VAS; and time to achieve pain improvement thresholds were assessed over 52 weeks, as were Patient Global Assessment (PtGA) and 36-Item Short Form Health Survey Physical Component Score (SF-36 PCS) outcomes. RESULTS: Baricitinib monotherapy or combination with MTX provides greater (least square mean changes (LSM) from baseline -40 mm and -43 mm, respectively) and more rapid (median 12 and 8 weeks to ≥70% improvement, respectively) pain relief than MTX alone (LSM -31 mm, median 20 weeks to ≥70% improvement) over 52 weeks. Baricitinib, alone or combination, provides 9-10 additional weeks of limited to no pain, similar gain in achievable wellness measured through PtGA, and 5-7 additional weeks with change in SF-36 PCS ≥5 vs MTX over 1 year. CONCLUSIONS: Patients treated with baricitinib reported significantly greater and more rapid pain relief, more weeks with limited to no pain, and clinically meaningful improvements in physical health than patients treated with MTX alone over 1 year.

Safety of baricitinib for the treatment of rheumatoid arthritis over a median of 4.6 and up to 9.3 years of treatment: final results from long-term extension study and integrated database.

OBJECTIVE: To report long-term safety from the completed extension trial of baricitinib, an oral selective Janus kinase inhibitor, in patients with active rheumatoid arthritis (RA). METHODS: Treatment-emergent adverse events are summarised from an integrated database (9 phase III/II/Ib and 1 long-term extension) of patients who received any baricitinib dose (All-bari-RA). Standardised incidence ratio (SIR) for malignancy (excluding non-melanoma skin cancer (NMSC)) and standardised mortality ratio (SMR) were estimated. Additional analysis was done in a subset of patients who had ever taken 2 mg or 4 mg baricitinib. RESULTS: 3770 patients received baricitinib (14 744 patient-years of exposure (PYE)). All-bari-RA incidence rates (IRs) per 100 patient-years at risk were 2.6, 3.0 and 0.5 for serious infections, herpes zoster and major adverse cardiovascular events (MACE), respectively. In patients aged ≥50 with ≥1 cardiovascular risk factor, the IR for MACE was 0.77 (95% CI 0.56 to 1.04). The IR for malignancy (excluding NMSC) during the first 48 weeks was 0.6 and remained stable thereafter (IR 1.0). The SIR for malignancies excluding NMSC was 1.07 (95% CI 0.90 to 1.26) and the SMR was 0.74 (95% CI 0.59 to 0.92). All-bari-RA IRs for deep vein thrombosis (DVT)/pulmonary embolism (PE), DVT and PE were 0.5 (95% CI 0.38 to 0.61), 0.4 (95% CI 0.26 to 0.45) and 0.3 (95% CI 0.18 to 0.35), respectively. No clear dose differences were noted for exposure-adjusted IRs (per 100 PYE) for deaths, serious infections, DVT/PE and MACE. CONCLUSIONS: In this integrated analysis including long-term data of baricitinib from 3770 patients (median 4.6 years, up to 9.3 years) with active RA, baricitinib maintained a similar safety profile to earlier analyses. No new safety signals were identified. TRIAL REGISTRATION NUMBER: NCT01185353, NCT00902486, NCT01469013, NCT01710358, NCT02265705, NCT01721044, NCT01721057, NCT01711359 and NCT01885078.

Factors Associated with Health-Related Quality of Life in Psoriatic Arthritis Patients: A Longitudinal Analysis.

INTRODUCTION: Psoriatic arthritis (PsA) is considered a multifaceted disease, with patients reporting low health-related quality of life (HRQoL). Data on disease burden are substantial and there exists a need for properly designed studies to learn more about the evolution of HRQoL in this condition. This study aims to identify factors associated to HRQoL evolution in PsA patients followed-up in a real-world setting in Spain. METHODS: We conducted a retrospective longitudinal observational study including incident patients from the rheumatology outpatient clinic of Hospital Clínico San Carlos (Madrid, Spain), diagnosed for the first time of PsA, defined as having received any ICD9/ICD10 diagnosis code of PsA, from 2007 to 2016, and followed-up until loss of follow-up, death, or November 2017. The influence of demographic and clinical variables in baseline HRQoL [assessed with the Rosser Classification Index (RCI)] was analyzed using bivariable and multivariable generalized linear models. The influence of those variables and of treatment-related factors in repeated measures of HRQoL was analyzed using bivariable and multivariable generalized estimating equations (GEE) models nested by patient. RESULTS: Two hundred and thirty patients were included in the analysis, with 3384 registered visits. At baseline, older age, a previous diagnosis of obesity, and the presence of enthesitis were significantly associated with worse HRQoL. During follow-up, using an exchangeable working correlation structure, the presence of enthesitis was also associated with worse HRQoL, coefficient (95% CI) - 0.006 (- 0.01 to - 0.002), p = 1.00E-03; conversely, treatment with methotrexate or antimalarials was associated with better HRQoL with 0.007 (0.001-0.014), p = 0.020 and 0.003 (0.001-0.005), p = 3.00E-03, respectively. CONCLUSIONS: Musculoskeletal manifestations and comorbidities exert a deleterious effect in HRQoL of PsA patients. Therefore, the optimal management of this condition needs to also address these manifestations in order to try to restore the QoL of these patients.

Patient Experiences, Satisfaction, and Expectations with Current Systemic Lupus Erythematosus Treatment: Results of the SLE-UPDATE Survey.

OBJECTIVES: To provide information on systemic lupus erythematosus (SLE) patients' experiences, satisfaction, and expectations with treatments and examine the association between treatment satisfaction and patient-reported outcomes (PRO). METHODS: A cross-sectional, non-interventional, online survey of US adult patients with SLE was conducted in 2019. The survey consisted of 104 questions about SLE and the following PRO instruments: LupusPRO™, Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue, Work Productivity and Activity Impairment (WPAI), an 11-point Worst Pain Numerical Rating scale (NRS), and an 11-point Worst Joint Pain NRS. RESULTS: Five hundred participants (75% female, 76% White/Caucasian, mean age 42.6 ± 12.7 years, 63% with an associate degree or higher) completed the survey. Most participants were "completely" or "somewhat satisfied" with their treatments, although satisfaction rates were lower for corticosteroids (65%), immunosuppressants (71%), and anti-malarials (55%) than for belimumab (intravenous or subcutaneous) (86%) and rituximab (94%). Treatments were more often considered "burdensome" or "very burdensome" for belimumab (67%) and rituximab (63%) than for corticosteroids (48%), immunosuppressants (49%), and anti-malarials (30%). Pain and productivity assessments supported substantial impairment for the majority of participants, even those who indicated that they were completely satisfied with treatments. The treatment goals most commonly reported as "very important" were reducing fatigue, pain, and the frequency or severity of flares. Three-quarters of participants (76.6%) indicated that their physician's goals for their therapy matched their own goals "very" or "somewhat closely." Despite high levels of satisfaction, most participants (63.0%) indicated that their physicians had not asked about their treatment goals during the past 3 months. CONCLUSION: SLE patients reported high rates of satisfaction with current therapies despite identifying substantial treatment burdens, residual pain, and fatigue. Reduced fatigue, pain, and flares were the most important treatment goals for these patients.

Corticosteroid dosing and opioid use are high in patients with SLE and remain elevated after belimumab initiation: a retrospective claims database analysis.

OBJECTIVES: To investigate corticosteroid and opioid use among patients with SLE and to examine the impact of belimumab initiation on the use of other SLE therapies. METHODS: We identified adult patients with SLE (International Classification of Diseases, 9th Revision/10th Revision 710.0 and M32) between 1 January 2012 and 31 May 2018 (earliest SLE diagnosis=index date) within MarketScan administrative claims data. Patients were followed from index date for a minimum of 12 months and until the earlier of disenrolment in their health plan or study end (31 May 2018). Corticosteroid utilisation, corticosteroid dose (in prednisone equivalents) and opioid utilisation (overall, by strength (weak, strong) and by duration (chronic use defined as >90 days of cumulative drug supply)) were measured during follow-up. Oral corticosteroid and opioid use were compared in the 6 months before and after initiation of belimumab. RESULTS: There were 49 413 patients with SLE eligible for analysis (mean (SD) age: 50.1 (14.0) years, 90.2% female). Of these, 68.5% received corticosteroids, and the average number of prescriptions was 4.59 (4.11) over the first 12 months of follow-up. Among patients with oral corticosteroids, average daily dose was 19.4 (14.2) mg and 59.6% had an average daily dose of ≥15 mg. Half (52.6%) had at least one opioid prescription and of these, 34.6% had chronic use over the first 12 months of follow-up. Among patients initiating belimumab during follow-up (n=1710), oral corticosteroid use decreased by 9.1% (p=0.001), and average daily dose decreased from 14.5 (18.4) mg to 11.9 (18.0) mg (p<0.001) in the 6 months after initiation compared with the 6 months prior. Initiation of belimumab had no impact on prevalence of opioid use. CONCLUSIONS: A high proportion of patients with SLE are treated with corticosteroids to control SLE and opioid therapy to manage chronic pain. While there was no change in opioid use, oral corticosteroid use and dose intensity decreased following initiation of belimumab.

To what extend is nail ultrasound discriminative between psoriasis, psoriatic arthritis and healthy subjects?

To assess the discriminative utility of nail features detected by B-mode (BM) and color Doppler (CD) ultrasound (US) between patients with psoriasis (PsO) and psoriatic arthritis (PsA) and healthy controls. Sixty patients with PsA, 21 patients with PsO, and 20 healthy controls were prospectively included. All patients underwent a dermatologic assessment and PsA patients also a rheumatologic assessment. All patients and controls underwent a US assessment of the finger nails that included a BM score for nail plate integrity and four different CD scores based on the amount and location of CD signals in the nail bed/matrix. In addition, we measured the thickness of the nail bed (TNB) and nail plate (TNP). The BM score and the CD score based on the amount of signals in the nail bed in contact with the ventral plate discriminated between the control group (median, range 0.0, 0-4 and 2.0, 0-9, respectively) and the PsO/PsA group (median, range: 7.0, 0-31 and 5.14, 0-13, respectively) (p < 0.05) with or without clinical nail involvement. The CD scores based on the percentage of the nail bed/matrix occupied by Doppler signals did not discriminate between controls and PsO/PsA patients. TNB and TNP were significantly higher in psoriatic nails with or without clinical involvement than in control nails. In PsO/PsA patients, the BM score, TNB and TNP were significantly higher in clinically involved nail than in clinically non-involved nails. Our results showed discriminative utility of BM US and some CD US features for PsO/PsA nails.

Vitamin D levels and their impact on mineral metabolism in HIV infected patients: an exploratory study.

Vitamin D has immunomodulating properties. The nuclear receptor for vitamin D is expressed in several immune cells, which convert 25-hydroxyvitamin D (25OHD) to the active form 1,25 hydroxyvitamin D [1,25(OH)2 D]. Under conditions of infection, 1,25(OH)2 D promotes production of cathelicidin (an antimicrobial peptide) in monocytes and activated macrophages. In vitro studies have shown the ability of cathelicidin to inhibit replication of human immunodeficiency virus (HIV-1) in T CD4 lymphocytes and macrophages. OBJECTIVE: To evaluate vitamin D levels and their impact on mineral metabolism in HIV infected patients. MATERIALS AND METHODS: Seventy-four clinical records of HIV/AIDS patients seen at the outpatients clinic were reviewed. The following data were collected: age, sex, time since diagnosis of HIV, HIV-1 viral load, CD4 counts (absolute value and percentage), and mineral metabolism determinations: 25OHD, intact parathormone (iPTH); serum calcium (sCa); serum phosphorus (sP) and serum crosslaps (sCTX). Vitamin D levels were stratified as follows: optimal: ≥30ng/ml; insufficient: 21-29ng/ml; moderately deficient: 20≥ -25OHD- >10 ng/ml and severely deficient ≤10 ng/ml. RESULTS: Fifty-five clinical records were included; 82% of patients had 25OHD levels below 30ng/ml (insufficient: 23.6%, moderately deficient: 36.4%; and severely deficient: 21.8%). A significantly higher serum PTH levels in the moderately and severely deficient groups than in the optimal and insufficient groups was observed (p<0.05 and p<0.03 respectively). A weak negative correlation was observed between serum 25OHD and PTH levels (r=-0.268; p<0.004). CONCLUSION: Sub-optimal vitamin D levels are frequently observed in HIV/AIDS patients on antiretroviral therapy (ART). Systematic assessment of mineral metabolism is considered necessary in HIV/AIDS positive patients.

Increase in IS256 transposition in invasive vancomycin heteroresistant Staphylococcus aureus isolate belonging to ST100 and its derived VISA mutants.

In Staphylococcus aureus, transposition of IS256 has been described to play an important role in biofilm formation and antibiotic resistance. This study describes the molecular characterization of two clinical heterogeneous vancomycin-intermediate S. aureus (hVISA) isolates recovered from the same patient (before and after antibiotic treatment) and two VISA derivatives obtained by serial passages in the presence of vancomycin. Our results showed that antibiotic treatment (in vivo and in vitro) could enhance IS256 transposition, being responsible for the eventual loss of agr function. As far as we know this is the first study that reports the increase of IS256 transposition in isogenic strains after antibiotic treatment in a clinical setting.

Structural damage in rheumatoid arthritis: comparison between tendon damage evaluated by ultrasound and radiographic damage.

OBJECTIVE: To compare structural damage assessed by conventional radiography and tendon damage assessed by musculoskeletal US (MSUS) at wrist and ankle in RA patients. METHODS: We evaluated 72 consecutive patients [56 (77.8%) females] with RA. The MSUS evaluation consisted in a B-mode examination of bilateral extensor carpi ulnaris and tibialis posterior tendons. Tendon damage was defined and scored according to OMERACT. A total score for the tendon damage score (TDS) was calculated by summing the grades for each tendon. For the radiographic evaluations we used the van der Heijde score; a total radiographic score (RTS) was calculated by summing a bone erosion score (ERS) and a joint space narrowing score (JSNS). RESULTS: We evaluated 288 tendons. The mean (s.d.) of TDS was 2.3 (1.8). Fifty-four (75%) patients presented tendon damage of at least one tendon. From all evaluated tendons, 134 (46.5%) had no tendon damage, 146 (50.7%) had grade 1 and 8 (2.8%) had grade 2 tendon damage. The mean (s.d.) for RTS was 91.4 (97), for ERS was 47.3 (61.9) and for JSNS was 44.1 (37.2). We found a significant correlation between disease duration and both TDS and RTS (r = 0.413 and r = 0.560, respectively; P < 0.0001). We found a good significant correlation between TDS and all variables of radiographic structural damage (RTS, r = 0.65; ERS, r = 0.637; JSNS, r = 0.618; P < 0.001). CONCLUSION: The MSUS assessment of only four tendons can be an additional feasible method to assess structural damage in RA patients.

Evaluation of the impact of fibromyalgia in disease activity and treatment effect in spondyloarthritis.

BACKGROUND: Fibromyalgia (FM) can coexist with Spondyloarthritis (SpA) leading to diagnostic and treatment dilemmas, especially in the presence of enthesitis. With this study we aimed to estimate the prevalence of FM in SpA and to compare the clinical/disease features and TNF inhibitors (TNFi) in patients with/without FM. METHOD: FM was defined by a score = > 5/6 of the Fibromyalgia Rapid Screening Tool (FiRST). SpA patients (according to the rheumatologist) and consecutively consulting in the day care hospital but also in the outpatient clinic at the rheumatology department of a tertiary care university hospital were included. Demographics, disease characteristics, activity and severity and TNFi treatment were compared in patients with and without FM; retention rate of the first TNFi and associated factors were explored (Kaplan Meier and Cox regression). RESULTS: Of the 196 enrolled SpA patients, 42 (21.4 %) were positively screened for FM. No statistically significant differences in the prevalence of FM were found with regard to the fulfillment of the ASAS criteria for peripheral/axial SpA, nor with regard to the fulfillment of the imaging vs. clinical arm of the ASAS criteria. However, patients with coexisting FM presented significantly with more enthesitis, higher disease activity (BASDAI and VAS) and poorer function scores (BASFI). No differences were found with regard to the initiation of TNFi treatment (79.0 % vs. 70.0 %, respectively), but the retention rate of the first TNFi after 2 years was shorter in the group of patients with FM (28.1 % (95 % CI 12.5-44.0) vs. 41.7 % (95 % CI 32.2-51.3), p = 0.01). CONCLUSION: This study confirms that coexistent FM in SpA might impact the patient-reported outcome indices for disease activity and function, and the retention rate of TNFi treatment.

Ultrasound-detected activity in rheumatoid arthritis on methotrexate therapy: Which joints and tendons should be assessed to predict unstable remission?

The aim of the study was to investigate the predictive value of different reduced joint ultrasound (US) assessments of synovitis and tenosynovitis in relation to unstable remission in a cohort of rheumatoid arthritis (RA) patients on methotrexate therapy. Forty-seven RA patients (38 women, 9 men), being treated with methotrexate (MTX), in clinical remission as judged by their consultant rheumatologist were evaluated for disease activity according to the Disease Activity Score (DAS) 28 at baseline and 6 months. Sustained remission and unstable remission were defined according to the baseline and 6-month DAS28 and changes in RA therapy during the follow-up. Each patient underwent at baseline a B-mode and power Doppler (PD) assessment of 44 joints and 20 tendons/tendon compartments by a rheumatologist blinded to the clinical and laboratory data. B-mode synovial hypertrophy (SH), synovial PD signal, B-mode tenosynovitis, and Doppler tenosynovitis were scored 0-3. The presence and index of synovial PD signal in 44 joints [odds ratio (OR) 8.21 (p = 0.016) and OR 2.20 (p = 0.049), respectively] and in 12 joints [OR 5.82 (p = 0.041) and OR 4.19 (p = 0.020), respectively], the presence of SH in wrist and MCP joints [OR 4.79 (p = 0.045)], and the presence of synovial PD signal in wrist-MCP-ankle-MTP joints [OR 4.62 (p = 0.046)] were predictors of unstable remission. The 12-joint or wrist-hand-ankle-MTP US assessments can predict unstable remission in RA patients in apparent clinical remission being treated with MTX.

Predictive value of Doppler ultrasound-detected synovitis in relation to failed tapering of biologic therapy in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the predictive value of synovitis detected by Doppler US in relation to failed tapering of biologic therapy (BT) in RA patients in sustained clinical remission. METHODS: A total of 77 RA patients (52 women, 25 men) in sustained clinical remission, treated with a stable dosage of BT were prospectively recruited. BT was tapered according to an agreed strategy implemented in clinical practice (i.e. increasing the interval between doses for s.c. BT and reducing the dose for i.v. BT). BT tapering failure was assessed at 6 and 12 months. Doppler US investigation of 42 joints for the presence and grade (0-3) of B-mode synovial hypertrophy and synovial power Doppler signal (i.e. Doppler synovitis) was performed at baseline by a rheumatologist blinded to clinical and laboratory data. Hand and foot radiographs were obtained at baseline and at 12-month follow-up. RESULTS: Of the 77 patients, 46 (59.7%) were on s.c. BT and 31 (40.3%) on i.v. BT. At 12 months, 35 patients (45.5%) presented BT tapering failure, 23 of them (29.9% of all patients) in the first 6 months of BT tapering. In logistic regression analysis, the baseline DAS28 and the global score of Doppler synovitis were identified as independent predictors of BT tapering failure at 12 and 6 months. The presence of Doppler synovitis was the strongest predictor for BT tapering failure. No patient showed radiographic progression. CONCLUSION: Our results suggest that the presence of Doppler-detected synovitis may predict BT tapering failure in RA patients in sustained clinical remission.

Comparison between full and tapered dosages of biologic therapies in psoriatic arthritis patients: clinical and ultrasound assessment.

The primary objective of this study was to describe and compare clinical and musculoskeletal (MS) ultrasound (US) features between psoriatic arthritis (PsA) patients treated with full and tapered dosage of biologic (b) disease-modified antirheumatic drugs (DMARDs). The secondary objective was to compare clinical and MSUS features between PsA patients treated with bDMARDs with and without concomitant synthetic (s) DMARDs. We evaluated 102 patients with PsA treated with bDMARDs. The bDMARD dosage tapering had been made in patients with a maintained remission or minimal disease activity (MDA) according to their attending rheumatologist and with the patient acceptance. The bDMARD tapering consisted of the following: increase the interval between doses for subcutaneous bDMARDs or reduction of the dose for intravenous bDMARDs. The clinical evaluation consisted of a dermatologic and rheumatologic assessment of disease activity. The presence of B-mode and Doppler synovitis, tenosynovitis, enthesopathy, and paratenonitis was investigated by a rheumatologist blinded to drug dosage, clinical assessments, and laboratory results. Seventy-four (72.5 %) patients received full dosage of bDMARDs and 28 (27.5 %) received tapered dosage. The duration with biologic therapy and with current biologic therapy was significantly higher in patients with tapered dosages (p = 0.008 and p = 0.001, respectively). We found no significant differences between clinical, laboratory, and US variables, both for BM and CD between patients with full and tapered dosage and between patients with and without concomitant sDMARD. Clinical assessment, MSUS variables, and MDA status are similar in patients receiving full and tapered dosage of bDMARDs.