Long-Term Follow-Up of Anti-Infliximab Antibodies in Patients With Radiographic Axial Spondyloarthritis: A Marker of Drug Survival and Tapering.

OBJECTIVE: The aim of this study was to evaluate the influence of anti-infliximab (IFX) antibodies on three different points of care: response/tolerance to IFX, tapering strategy, and in a subsequent treatment with a second tumor necrosis factor inhibitor (TNFi). METHODS: A prospective cohort of 60 patients with radiographic axial spondyloarthritis who received IFX were evaluated retrospectively regarding clinical/laboratorial data, IFX levels, and anti-IFX antibodies at baseline, after 6, 12 to 14, 22 to 24, 48 to 54, 96 to 102 weeks, and before tapering or switching. RESULTS: Anti-IFX antibodies were detected in 27 patients (45%), of whom 23 (85.1%) became positive in the first year of IFX treatment. In comparison to the group that was negative for anti-IFX antibodies, patients who were positive for anti-IFX antibodies demonstrated the following: less use of methotrexate as a concomitant treatment to IFX (5 [18.5%] vs 14 [42.4%]; P = 0.048), more infusion reactions at 22 to 24 weeks (P = 0.020) and 48 to 54 weeks (P = 0.034), more treatment failures (P = 0.028) at 48 to 54 weeks, reduced overall IFX survival (P < 0.001), and lower sustained responses (P = 0.044). Of note, patients who were positive for anti-IFX antibodies exhibited a shorter tapering survival (9.9 months [95% confidence interval (CI) 4.0-15.8] vs 63.4 months [95% CI 27.9-98.8]; P = 0.004) in comparison with patients who were negative for anti-IFX antibodies. Conversely, for patients who failed IFX, patients who were positive for anti-IFX antibodies had better clinical response to the second TNFi at three months (15 [83.3%] vs 3 [27.3%]; P = 0.005) and six months (15 [83.3%] vs 4 [36.4%]; P = 0.017) than the patients who were negative for anti-IFX antibodies after switching. CONCLUSION: This study provided novel data that anti-IFX antibodies is a parameter for reduced tapering survival, reinforcing its detection to guide clinical decision. Additionally, we confirmed in a long-term cohort the anti-IFX antibody association with worse IFX performance and as predictor of the second TNFi good clinical response.

Barriers, Facilitators, and Strategies for Developing a Culturally Informed Lifestyle Intervention for Native Hawaiian, CHamoru, and Filipino Breast Cancer Survivors: Mixed-Methods Findings from Focus Group Participants.

Breast cancer disproportionately impacts Native Hawaiian, CHamoru, and Filipino women. Few culturally informed interventions addressing breast cancer survivors exist and none have been developed or tested specifically for Native Hawaiian, CHamoru, and Filipino women. This study aimed to conduct focus groups with Native Hawaiian, CHamoru, and Filipino women previously diagnosed with breast cancer to inform future research in Guam and Hawai'i. Convenience sampling and grounded theory approaches were used. Focus group sessions were conducted during summer 2023 and included questions to understand the barriers, motivators, and implementation recommendations for lifestyle interventions aimed at reducing the risk for breast cancer recurrence among the target population. Data saturation was reached after a total of seven focus groups (an average of four survivors/group per site) were conducted (three in Hawai'i and four in Guam), which represented 28 breast cancer survivors. Themes from the focus groups emerged around developing support systems with other survivors, providing physical activity and nutrition intervention activities and materials in multiple formats, and incorporating activities and foods that accommodate the side effects of breast cancer treatments and are culturally relevant. The average desired intervention length was eight weeks. These findings will inform the development and feasibility testing of a culturally informed lifestyle intervention for breast cancer survivors in Guam and Hawai'i.

Safety and immunogenicity of influenza A(H3N2) component vaccine in juvenile systemic lupus erythematosus

Abstract Introduction Seasonal influenza A (H3N2) virus is an important cause of morbidity and mortality in the last 50 years in population that is greater than the impact of H1N1. Data assessing immunogenicity and safety of this virus component in juvenile systemic lupus erythematosus (JSLE) is lacking in the literature. Objective To evaluate short-term immunogenicity and safety of influenza A/Singapore (H3N2) vaccine in JSLE. Methods 24 consecutive JSLE patients and 29 healthy controls (HC) were vaccinated with influenza A/Singapore/ INFIMH-16-0019/2016(H3N2)-like virus. Influenza A (H3N2) seroprotection (SP), seroconversion (SC), geometric mean titers (GMT), factor increase in GMT (FI-GMT) titers were assessed before and 4 weeks post-vaccination. Disease activity, therapies and adverse events (AE) were also evaluated. Results JSLE patients and controls were comparable in current age [14.5 (10.1-18.3) vs. 14 (9-18.4) years, p = 0.448] and female sex [21 (87.5%) vs. 19 (65.5%), p = 0.108]. Before vaccination, JSLE and HC had comparable SP rates [22 (91.7%) vs. 25 (86.2%), p = 0.678] and GMT titers [102.3 (95% CI 75.0-139.4) vs. 109.6 (95% CI 68.2-176.2), p = 0.231]. At D30, JSLE and HC had similar immune response, since no differences were observed in SP [24 (100%) vs. 28 (96.6%), p = 1.000)], SC [4 (16.7%) vs. 9 (31.0%), p = 0.338), GMT [162.3 (132.9-198.3) vs. 208.1 (150.5-287.8), p = 0.143] and factor increase in GMT [1.6 (1.2-2.1) vs. 1.9 (1.4-2.5), p = 0.574]. SLEDAI-2K scores [2 (0-17) vs. 2 (0-17), p = 0.765] and therapies remained stable throughout the study. Further analysis of possible factors influencing vaccine immune response among JSLE patients demonstrated similar GMT between patients with SLEDAI < 4 compared to SLEDAI ≥ 4 ( p = 0.713), as well as between patients with and without current use of prednisone ( p = 0.420), azathioprine ( p = 1.0), mycophenolate mofetil ( p = 0.185), and methotrexate ( p = 0.095). No serious AE were reported in both groups and most of them were asymptomatic (58.3% vs. 44.8%, p = 0.958). Local and systemic AE were alike in both groups ( p > 0.05). Conclusion This is the first study that identified adequate immune protection against H3N2-influenza strain with additional vaccine-induced increment of immune response and an adequate safety profile in JSLE. ( www.clinicaltrials.gov , NCT03540823).

Primary dental care treatment in primary Sjögren's syndrome: a possible role in improving salivary flow rate.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is an inflammatory chronic disorder that mainly affects exocrine glands. Additionally, oral infections can aggravate the glandular dysfunction. However, data on primary dental care (PDC) treatment in pSS are scarce. This study aimed to appraise the impact of PDC on the Xerostomia Inventory (XI), unstimulated/stimulated salivary flow rates and salivary cytokine profile in pSS. METHODS: Fifty-two pSS patients and 52 sex- and age-matched control participants without systemic autoimmune diseases were included in a prospective study. At inclusion, all participants were assessed through a standardised protocol, measurement of salivary pro-inflammatory cytokines, and underwent PDC. Dental procedures included: oral hygiene guidance, restorative treatment of caries, surgical removal of residual roots and impacted or partially erupted teeth, cysts, supra and subgingival periodontal scaling and treatment of soft tissue disorders (removal of lesions and treatment of opportunistic infections). After 3 months, the clinical/laboratorial assessments were repeated. RESULTS: At inclusion, the Decayed, Missing and Filled Teeth (DMFT) index was higher in the pSS patients than in the control group (13.3±8.2 vs. 8.6±6.2, p=0.002), whereas periodontal parameters were comparable in both groups (p>0.05). After PDC, 26.9% of pSS patients showed a reduction of at least 6 points (clinical improvement) in XI, but mean XI remained unchanged (p=0.285). PDC resulted in an increase in mean unstimulated (p<0.001) and stimulated (p=0.001) salivary flow rates in pSS, with no change in salivary cytokine profile (p≥0.05). CONCLUSIONS: PDC promoted improvement in unstimulated and stimulated salivary flow rates in pSS. This novel finding reinforces the recommendation of this strategy for pSS patients. CLINICALTRIALS: gov (Identifier: NCT03711214).

Abatacept induced long-term non-progressive reduction in gamma-globulins and autoantibodies: dissociation from disease activity control.

OBJECTIVES: To evaluate long-term effects on gamma-globulins and autoantibodies of abatacept (ABA) versus tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA) patients. METHOD: Eighteen RA patients undergoing abatacept (ABA-RA) and 18 age/sex-matched patients treated with TNFi (TNFi-RA) were compared regarding clinical data, total gamma-globulins (TGG), specific subtypes (IgG, IgM, IgA), free light chains (FLC), IgM/IgG rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP3), and anti-mutated citrullinated vimentin (anti-MCV), assessed before and every 6 months, up to 24 months. EXCLUSION CRITERIA: previous abatacept/rituximab or low TGG (< 0.7 g/dL). RESULTS: At baseline, female sex (78 vs. 78%), age (55 vs. 53 years), DAS28 (5.73 vs. 5.67), TGG (1.4 vs. 1.35 g/dL), IgG (1168 vs. 1079 mg/dL), IgM (107 vs. 113 mg/dL), IgA (333 vs. 322 mg/dL), kappa (342 vs. 249 mg/dL), lambda (170 vs. 150 mg/dL), IgM-RF (76 vs. 53 UI), IgG-RF (63 vs. 25 UI), anti-CCP3 (216 vs. 189 UI), and anti-MCV (202 vs. 102 UI) were comparable in ABA-RA and TNFi-RA (p > 0.05). Similar disease activity improvement was observed in both groups. In ABA-RA, significant decreases (p < 0.05) were observed in TGG (1.4 vs. 1.05 g/dL), IgG (1168 vs. 997), IgA (333 vs. 278 mg/dL), kappa (342 vs. 257 mg/dL), lambda (170 vs. 144 mg/dL), IgM-RF (76 vs. 37 UI), IgG-RF (65 vs. 24 UI), anti-CCP3 (216 vs. 183 UI), and anti-MCV (202 vs. 60 UI) at 6 months, without further decreases. In contrast, TNFi-RA showed no decrease in any of such parameters. ABA-RA also had more often transient IgG levels under the lower limit of normality (66.7% vs. 33.3%, p = 0.046). No severe infection occurred. DAS28, ESR, and CRP correlated significantly to gamma-globulins and FLC at baseline (p < 0.05), but these correlations were longitudinally lost in ABA-RA, but not in TNFi-RA. CONCLUSION: ABA, but not TNFi, induces a safe, persistent, long-term, and non-progressive reduction in gamma-globulins and autoantibodies, including anti-MCV. This pattern is dissociated from disease activity control.Key Points• ABA induces a long-term and non-progressive reduction in gamma-globulins and FLC, which occurs regardless of disease activity control.• ABA-induced reduction in gamma-globulins and FLC promotes a dissociation of such parameters and disease activity.• The same pattern of reduction is observed in autoantibodies: IgM-RF, IgG-RF, anti-CCP3, and anti-MCV.• Low transient IgG can be observed in RA patients treated with ABA, but does not correlate to infection.

Anti-adalimumab antibodies kinetics: an early guide for juvenile idiopathic arthritis (JIA) switching.

OBJECTIVE: To assess the longitudinal production of anti-adalimumab antibody (AAA) and baseline risk factors for this antibody development in juvenile idiopathic arthritis (JIA) patients initiating adalimumab (ADA). METHOD: Thirty consecutive JIA patients under ADA therapy were prospectively followed. JIA clinical/laboratorial/treatment data and sera for ADA and AAA assays (ELISA and bridging ELISA) were obtained at baseline (BL), 2 months (2M), 3 months (3M), 6 months (6M), 12 months (12M), and 24 months (24M). Patients with therapy failure requiring ADA withdrawn had their sera evaluated at their last medical visit prior to biologic switch (blinded to ADA and AAA levels). RESULTS: AAA was absent at BL, first detected at 2M after ADA initiation in 2/30 (7%) patients with a significant increase at 3M (10/29 (34%), p = 0.013) and no major change in 6M (11/30 (37%)) and 12M (9/26 (35%)). Of note, at 3M, AAA levels correlated negatively with ADA levels (r = - 0.781, p = 0.0001). Analysis of BL predictors revealed a significantly higher risk of developing AAA in patients with female gender (OR 21; 95% CI 1.08-406.57; p = 0.044), ESR > 30 mm/1st hour (OR 5.44; 95% CI 1.04-28.53; p = 0.045), and leflunomide use (OR 9.33; 95% CI 1.51-57.66; p = 0.016). In contrast, concomitant use of methotrexate was protective for AAA appearance (OR 0.08; 95% CI 0.01-0.53; p = 0.009). After 12M of ADA, 60% of AAA-positive patients required drug switch for drug failure compared with 15% in AAA-negative group (p = 0.03). CONCLUSIONS: This study provides novel evidence of AAA production kinetics demonstrating a timely significant increase starting at 3M and stable throughout 24M. We also identified female gender, increased ESR, and leflunomide use as relevant risk factors for AAA production at BL, whereas methotrexate was protective. Early systematic monitoring of AAA at 3M may, therefore, guide drug switching in these patients.Key Points• Anti-adalimumab antibodies (AAA) production kinetics demonstrated a timely significant increase starting at 3M in juvenile idiopathic arthritis (JIA) patients under adalimumab therapy• Female gender, increased ESR, and leflunomide use were identified as relevant risk factors for AAA production in JIA, whereas methotrexate was protective.

Is serum uric acid a predictor of long-term renal outcome in lupus nephritis?

BACKGROUND/OBJECTIVE: Recent studies observed an association between increased serum uric acid (SUA) levels and renal damage in lupus. However, the predictive value of UA for the development of long-term renal dysfunction in lupus nephritis (LN) is still unknown. The aim of this study was to evaluate if SUA may be a predictor of long-term renal outcome in LN. METHODS: Eighty biopsy-proven LN patients > 7 years of follow-up were selected. SUA levels were measured in sera stored at - 70 °C. All patients had serum stored from LN baseline, and 32 also had stored serum from 6 and 12 months after LN. Renal outcome was addressed after 7 years of follow-up to determine if SUA could be a predictor of long-term renal outcome. A good long-term renal outcome in 7 years was defined as a creatinine clearance (CrCl) ≥ 90.0 mL/min/1.73 m2, and poor if CrCl < 90 mL/min/1.73 m2. Patients were divided in two groups according to the renal outcome to assess whether SUA levels at different time points of follow-up could differentiate such groups. An ROC curve was plotted to assess accuracy. RESULTS: SUA levels at baseline and 6 months were not able to differentiate good from poor long-term renal outcomes in LN (respectively p = 0.37, p = 0.28), but at 12 months (p = 0.02), they could clearly differentiate the two groups. ROC curve (12 months) accuracy was 0.76. SUA cutoff was 6.05 mg/dL (sensitivity = 0.67, specificity = 0.89, positive predictive value = 0.85, negative predictive value = 0.73). CONCLUSION: SUA levels < 6.05 mg/dL at 12 months of follow-up is a predictor of good long-term renal outcome in lupus nephritis. KEY POINTS: • Previous studies reported an association between increased serum uric acid level and short-term renal damage in lupus patients. • The predictive value of serum uric acid for the development of long-term renal dysfunction in lupus nephritis was never assessed. • At 12 months of follow-up serum uric acid clearly differentiated good from poor long-term renal outcome in lupus nephritis. • SUA level < 6.05 mg/dL at 12 months of follow-up was a predictor of good long-term renal outcome in lupus nephritis.

Ovarian reserve in young juvenile idiopathic arthritis patients.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) occurs during reproductive age, however, there are no systematic data regarding ovarian function in this disease. METHODS: Twenty-eight post-pubertal JIA patients and age-matched 28 healthy controls were studied. Complete ovarian function was assessed during the early follicular phase of the menstrual cycle including anti-Müllerian hormone (AMH), estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and antral follicle count (AFC) by ovarian ultrasound, and anti-corpus lutheum antibodies (anti-CoL). Demographic data, menstrual abnormalities, disease parameters and treatment were also evaluated. RESULTS: The mean current age (22.6 ± 6.59 vs. 22.5 ± 6.59 years, p = .952) was similar in JIA patients and healthy controls with a higher median menarche age [13(8-16) vs. 12(8-14) years, p = .029]. A lower median AMH levels [2.65(0.47-9.08) vs. 4.83(0.74-17.24) ng/mL, p = .029] with a higher LH [8.44 ± 4.14 vs. 6.03 ± 2.80 IU/L, p = .014] and estradiol levels [52.3(25.8-227.4) vs. 38.9(26.2-133.6) pg/mL, p = .008] were observed in JIA compared to control group. Anti-CoL and AFC were similar in both groups (p > .05). Further analysis of JIA patients revealed that current age, disease duration, number of active/limited joints, ESR, CRP, patient/physician VAS, JADAS 71, DAS 28, CHAQ, HAQ, patient/parents PedsQL, PF-SF 36, cumulative glucocorticoid and cumulative methotrexate doses were not correlated with AMH, FSH, estradiol levels or AFC (p > .05). CONCLUSION: The present study was the first to suggest diminished ovarian reserve, not associated to hypothalamic pituitary gonadal axis, in JIA patients during reproductive age. The impact of this dysfunction in future fertility of these patients needs to be evaluated in prospective studies.

Weekly enrollment and usage patterns in an Internet smoking cessation intervention.

BACKGROUND: Previous analyses of Google search queries identified circaseptan (weekly) rhythms in smoking cessation information seeking, with Google searches for "quit" and "smoking" peaking early in the week. Similar patterns were observed for smoking cessation treatment seeking, such as calls to quitlines. These findings suggest that smoking cessation behaviors may have a weekly rhythm that could be leveraged to improve smoking cessation efforts. AIMS: To assess whether weekly enrollment and usage patterns exist for an Internet smoking cessation intervention. METHODS: We used process data from a large, longstanding Internet smoking cessation intervention (www.becomeanex.org). Pearson's chi-squared tests were performed to identify day-of-the week differences in enrollment, first visit to site community pages, and quit date. Differences were considered statistically significant at the 1% level if p < 0.00167 due to multiple comparisons. Regression analysis was used to examine differences in engagement activity based on the day of the week a user enrolled. RESULTS: Website users (n = 69,237) were more likely to enroll on the site at the beginning of the week (Mondays and Tuesdays) (p < 0.0001). Current smokers who selected quit dates (n = 5574) preferred quit dates that came early in the week (Sundays and Mondays) compared to other weekdays (p < 0.0001). Generally, there were no significant differences in overall website utilization metrics by day of enrollment, but there were some exceptions. Use of interactive features to select quit dates, track cigarette use, and record coping strategies was generally lower for Friday/Saturday enrollees. CONCLUSIONS: Consistent with prior research, the beginning of the week appears to be a time when individuals are more likely to enroll in an Internet smoking cessation intervention and engage with its core features. Emphasizing marketing and promotional efforts during the beginning of the week could result in greater reach of Internet smoking cessation interventions.

Global approaches to regulating electronic cigarettes.

OBJECTIVES: Classify and describe the policy approaches used by countries to regulate e-cigarettes. METHODS: National policies regulating e-cigarettes were identified by (1) conducting web searches on Ministry of Health websites, and (2) broad web searches. The mechanisms used to regulate e-cigarettes were classified as new/amended laws, or existing laws. The policy domains identified include restrictions or prohibitions on product: sale, manufacturing, importation, distribution, use, product design including e-liquid ingredients, advertising/promotion/sponsorship, trademarks, and regulation requiring: taxation, health warning labels and child-safety standards. The classification of the policy was reviewed by a country expert. RESULTS: The search identified 68 countries that regulate e-cigarettes: 22 countries regulate e-cigarettes using existing regulations; 25 countries enacted new policies to regulate e-cigarettes; 7 countries made amendments to existing legislation; 14 countries use a combination of new/amended and existing regulation. Common policies include a minimum-age-of-purchase, indoor-use (vape-free public places) bans and marketing restrictions. Few countries are applying a tax to e-cigarettes. CONCLUSIONS: A range of regulatory approaches are being applied to e-cigarettes globally; many countries regulate e-cigarettes using legislation not written for e-cigarettes.

Metabolic syndrome in Sjögren's syndrome patients: a relevant concern for clinical monitoring.

Metabolic syndrome (MetS) has been described in autoimmune diseases. However, there are scarce data about MetS and adipocytokine profile in primary Sjögren's syndrome (pSS). Seventy-one female pSS patients (American-European Consensus Group Criteria, 2002) aged 18-65 years and 71 age-, race-matched control women were enrolled in this case-control study. Clinical data were collected by a standardized protocol. Blood levels of glucose, cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglycerides, interleukin-1beta (IL-1beta)/IL-6, B-cell activating factor (BAFF), insulin, and leptin/adiponectin/visfatin/resistin were determined. Patients and controls were comparable regarding body mass index (BMI), smoking, sedentariness, and menopause (p > 0.05). MetS (39.4 vs. 16.9 %, p = 0.005), hypertension (p = 0.004), and dyslipidemia (p = 0.002) were more frequent in patients than controls. IL-1beta, IL-6, BAFF, resistin, and adiponectin levels were higher in patients than controls (p < 0.05). pSS patients with MetS (n = 28) had higher BMI, waist circumference, cholesterol, LDL-C, triglycerides, insulin, leptin and HOMA-IR values, and greater hypertension and diabetes rates than pSS patients without MetS (n = 43) (p < 0.05). Current and/or previous prednisone use (75.0 vs. 62.8 %, p = 0.313), current (3.0 ± 4.5 vs. 1.6 ± 3.2 mg/day, p = 0.299), and cumulative prednisone doses (p = 0.495) were similar in both groups. Otherwise, IL-1beta level was higher in MetS patients than in non-MetS patients (p = 0.012), and this finding was confirmed (p = 0.048) by multivariate analysis with adjustments for age, ethnicity, prednisone use, current and cumulative prednisone doses, and duration of use. We identified high MetS frequency and abnormal adipocytokine profile in pSS. The association of MetS with elevated IL-1beta level suggests that inflammation plays an important role in its pathogenesis.

Characterizing periodic messaging interventions across health behaviors and media: systematic review.

BACKGROUND: Periodic prompts serve as tools for health behavior interventions to encourage and maintain behavior changes. Past literature reviews have examined periodic messages targeting specific behaviors (smoking, physical activity, diet, etc) or media (telephone, email, face-to-face, newsletter, etc) and have found them to be effective in impacting health behavior in the short term. OBJECTIVE: Our goal was to review the literature related to periodic messaging and prompts in order to explore typical characteristics, assess the role of prompt timing, identify common theoretical models used, and identify characteristics associated with the effectiveness of periodic prompts. METHODS: Electronic searches of PubMed, PsycINFO, CINAHL, and Web of Science were conducted in October 2012 and May 2013. Database search terms included variant terms for periods, prompts, interventions, media, and health behaviors. RESULTS: Forty-two of the 55 included research articles found that prompts resulted in significant positive behavioral outcomes for participants. Prompts were delivered via text messages, email, mailed communications, and in a few instances via phone. Generally, the provision of feedback and specific strategies to accomplish behavior change appears to be important for the success of periodic prompts. Rationale for prompt timing was rarely provided, although some studies did organize message content around days of the week or times perceived to be high risk for particular behaviors. Smoking cessation interventions tended to be organized around quit date. Among studies using theoretical models to inform their interventions, the transtheoretical model was most common. CONCLUSIONS: Periodic messaging interventions yield positive results for short-term health behavior changes. Interventions including feedback and prompts that included strategies were more likely to report significantly positive outcomes. Work remains to better understand elements that make periodic prompts successful and whether they are effective in producing long-term outcomes.

Dependence measures for non-cigarette tobacco products within the context of the global epidemic: a systematic review.

OBJECTIVES: Validated metrics of tobacco dependence exist, but their value for global surveillance of tobacco dependence and development of tobacco control interventions is not well understood. This paper reviews tobacco dependence metrics for non-cigarette products, and whether measures of tobacco dependence have been validated in low-income and middle-income countries (LMIC). DATA SOURCES: Searches were conducted in PubMed, Scopus, PsycINFO, EMBASE, CINAHL and Global Health databases using variant terms for types of tobacco, dependence, measures and validity/reliability. Articles discussing dependence theories and/or metrics were fully reviewed and synthesised. STUDY SELECTION: Searches yielded 2702 unique articles. Two independent coders identified 587 articles for abstract review, and 229 were subsequently fully reviewed. Findings from 50 eligible papers are summarised. DATA EXTRACTION: An initial thematic analysis concentrated on four concepts: general tobacco dependence, dependence metrics, tobacco dependence in LMIC and dependence on non-cigarette tobacco. DATA SYNTHESIS: Analysis identified 14 distinct tobacco dependence instruments. Existing metrics treat tobacco dependence as multifaceted. Measures have been developed almost exclusively around cigarette smoking, although some validation and application across products has occurred. Where cross-national validation has occurred, however, this has rarely included LMIC. CONCLUSIONS: For purposes of global surveillance of tobacco dependence, there is a compelling need for validated measures to apply universally across social contexts and a multitude of tobacco products. Alternatively, effective tobacco control interventions require validated dependence measures that integrate specific behavioural elements and social context of product use. While different measures of dependence are required to fulfil each of these goals, both have value in addressing the global tobacco epidemic.

EBV reactivation serological profile in primary Sjögren's syndrome: an underlying trigger of active articular involvement?

Antibody to Epstein-Barr virus (EBV) early antigen diffuse (anti-EA-D) is associated with viral replication. However, their possible associations with clinical/therapeutic features in primary Sjögren's syndrome (pSS) were not established. We evaluated 100 pSS patients (American-European Criteria) and 89 age/gender/ethnicity-matched healthy controls. Disease activity was measured by EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). Antibodies to EBV (anti-VCA IgG/IgM, anti-EBNA-1 IgG, anti-EA-D IgG) were determined by ELISA. Patients and controls had comparable frequencies and mean levels of anti-VCA IgG (90 vs. 86.5 %, p = 0.501; 2.6 ± 1.1 vs. 2.5 ± 1.1 AU/mL, p = 0.737) and anti-EBNA-1 IgG (92 vs. 94.4 %, p = 0.576; 141.3 ± 69.8 vs. 135.6 ± 67.5 RU/mL, p = 0.464). Anti-VCA IgM was negative in all cases. Noteworthy, higher frequency and increased mean levels of anti-EA-D were observed in patients than controls (36 vs. 4.5 %, p < 0.0001; 38.6 ± 57.4 vs. 7.9 ± 26.3 RU/mL, p < 0.0001). Further analysis of patients with (n = 36) and without (n = 64) anti-EA-D revealed comparable age/gender/ethnicity (p ≥ 0.551), current prednisone dose (4.8 ± 6.9 vs. 5.1 ± 10.4 mg/day, p = 0.319), and current uses of prednisone (52.8 vs. 37.5 %, p = 0.148) and immunosuppressants (44.4 vs. 31.3 %, p = 0.201). ESSDAI values were comparable (p = 0.102), but joint activity was more frequent (25 vs. 9.4 %, p = 0.045) in anti-EA-D positive patients. Anti-EA-D antibodies were not associated with anti-Ro/SSA (p = 1.000), anti-La/SSB (p = 0.652), rheumatoid factor (p = 1.000), anti-α-fodrin (p = 0.390) or antiphospholipid antibodies (p = 0.573), not suggesting cross-reactivity. The higher anti-EA-D frequency associated with joint activity raises the possibility that a subclinical EBV reactivation may trigger or perpetuate the articular involvement in pSS.

Antibodies to ribosomal P proteins in lupus nephritis: a surrogate marker for a better renal survival?

OBJECTIVE: To define if antibodies to ribosomal P proteins disclose a better lupus nephritis long-term survival. METHODS: Sixty consecutive SLE patients with biopsy-proven nephritis (2004 ISN/RPS) were evaluated for renal survival parameters. Inclusion criteria were at least one serum sample at: renal flares, biopsy, and last follow-up until 2008. Anti-P was detected by ELISA/immunoblot and anti-dsDNA by indirect immunofluorescence/ELISA. RESULTS: Eleven patients (18%) with anti-P+ (without anti-dsDNA) during renal flare were compared to 49 (82%) persistently negative for anti-P throughout the study. At the final follow-up post-biopsy (6.3±2.5 vs. 6.8±2.4 years, p=0.36), the comparison of anti-P+/anti-dsDNA- with anti-P- group revealed a trend to lower mean creatinine levels (0.9±0.3 vs. 2.3±2.1 mg/dl, p=0.07), lower frequency of dialysis (0% vs. 35%, p=0.025), and higher frequency of normal renal function (91% vs. 53%, p=0.037). The overall renal survival was significantly higher in anti-P+/anti-dsDNA- compared to anti-P- (11.0±4.5 vs. 9.2±4.5 years, p=0.033), anti-dsDNA+/anti-P- (vs. 8.7±4.7 years, p=0.017), and anti-P-/anti-dsDNA- (vs. 9.8±4.3 years, p=0.09) groups. CONCLUSION: Our data supports the notion that anti-P antibody in the absence of anti-dsDNA during nephritis flares is a valuable marker to predict a better long-term renal outcome in lupus patients.

Comprometimento da habilidade verbal no lúpus eritematoso sistêmico juvenil / Verbal ability impairment in juvenil e systemic lupus erythematosus

INTRODUÇÃO/OBJETIVO: Avaliar a frequência do comprometimento da habilidade verbal e possíveis fatores associados em pacientes portadores de Lúpus Eritematoso Sistêmico Juvenil (LESJ). PACIENTES E MÉTODOS: Estudo transversal de 36 crianças e adolescentes com LESJ, de um grupo de 57 pacientes, do Ambulatório de Reumatologia do Departamento de Pediatria e Clínica Médica da Santa Casa de Misericórdia de São Paulo. Por ocasião do diagnóstico e do estudo, foram analisados aspectos epidemiológicos, clínicos, socioeconômicos e de escolaridade. Os pacientes foram submetidos a testes cognitivos e exames laboratoriais, e foram avaliadas medidas de atividade da doença (SLEDAI) e do dano cumulativo (SLICC-DI) e o tratamento com corticoesteroide. Os pacientes foram submetidos a testes cognitivos (escalas Weschler de inteligência: WISC III e WAISS III), e os resultados foram avaliados de acordo com os aspectos epidemiológicos, clínicos, laboratoriais e terapêuticos. RESULTADOS: A média de idade ao diagnóstico foi de 11,2 ± 2 anos, a idade na época do estudo de 15,4 ± 4,7 anos, com 89 por cento do sexo feminino. Houve predomínio de pacientes da classe socioeconômica C (61,1 por cento). O comprometimento cognitivo detectado nesses pacientes foi frequente (58,3 por cento), sendo o comprometimento da habilidade verbal um dos domínios cognitivos mais constantes. Encontrou-se associação do comprometimento da habilidade verbal com baixa condição socioeconômica e dano cumulativo (P < 0,05), mas não com atividade da doença, presença de autoanticorpos e dose de corticoesteroide (P > 0,05). CONCLUSÕES: Alteração da habilidade verbal é frequente no LESJ e está associada à condição socioeconômica e ao dano cumulativo, devendo ser suspeitada e investigada, principalmente por se tratar de pacientes pediátricos, para que não haja comprometimento da qualidade de vida na fase adulta. Como não está relacionado à atividade da doença ou à presença de autoanticorpos, deve ser sempre avaliado na presença ou não desses fatores. Da mesma forma, deve-se avaliar independentemente das doses de corticoesteroide por não haver associação.

INTRODUCTION/OBJECTIVE: Evaluate the frequency of verbal ability impairment and associated factors in patients with juvenile systemic lupus erythematosus (JSLE). PATIENTS AND METHODS: Cross sectional study of 36 children and adolescents with JSLE of a group of 57 patients at the Clinic of Rheumatology, Department of Pediatrics and Medical Clinic of Santa Casa de Misericórdia de São Paulo. At the time of diagnosis and study, we analyzed the following epidemiological features: clinical, socioeconomic, and educational level. Patients underwent cognitive and laboratory tests and we assessed disease activity (SLEDAI), cumulative damage (SLICC-DI), and treatment with corticosteroids. The patients underwent cognitive tests (Wechsler Intelligence Scales: WISC III and Waiss III), and the results were evaluated according to epidemiological, clinical, laboratory and treatment features. RESULTS: The mean age at diagnosis was 11.2 ± 2 years and at the time of the study the mean age was 15.4 ± 4.7 years. There was predominance of women (89 percent) and of socioeconomic class C patients (61.1 percent). The cognitive impairment found in these patients was frequent (58.3 percent), affecting more often the verbal ability. We found association of verbal ability impairment with low socioeconomic status and cumulative damage (P < 0.05), but not with disease activity, presence of autoantibodies, and dose of corticosteroids (P > 0.05). CONCLUSIONS: Change in verbal ability is frequent in JSLE and is associated with socioeconomic status and cumulative damage, and should be suspected and investigated, particularly in pediatric patients to avoid quality of life impairment in adulthood. As it is not related with disease activity or presence of autoantibodies, it should always be assessed in the presence or absence of these factors. Likewise, the doses of corticosteroids should be independently evaluated.

Estudo longitudinal do anticorpo antilipoproteína lipase e sua relação com atividade de doença nos indivíduos com lúpus eritematoso sistêmico sem anticorpos anti-dsDNA / Longitudinal fluctuation of anti-lipoprotein lipase antibody is related with disease activity in systemic lupus erythematosus patients without anti-dsDNA antibodies

INTRODUÇÃO: O Lúpus Eritematoso Sistêmico (LES) se caracteriza por períodos de exacerbação e remissão clínica que frequentemente são acompanhados por alterações nos níveis séricos de anticorpos específicos, como o anti-dsDNA, que está presente em 40 por cento dos casos, associado principalmente à atividade renal. Recentemente houve a descrição de duas subpopulações de anticorpos antilipoproteína lipase (anti-LPL) no LES: uma com e a outra sem atividade anti-dsDNA. A possível relação desse último grupo de anticorpos com a atividade inflamatória de doença ainda não foi analisada no LES. OBJETIVOS: Avaliar longitudinalmente a associação dos níveis séricos dos anticorpos anti-LPL com atividade do LES em pacientes com anti-dsDNA persistentemente negativo. PACIENTES E MÉTODOS: Cinco pacientes com LES com anti-dsDNA persistentemente negativo mensurado por ELISA e por imunofluorescência indireta em crithidia luciliae e altos títulos de anti-LPL por ELISA (> 5 desvios-padrão (DP) da média de 20 controles normais) foram selecionados e acompanhados longitudinalmente durante um período mínimo de dois anos. RESULTADOS: Caso 1: Homem, 24 anos com LES desde 2001 apresentou hemorragia alveolar, proteinúria, hipertensão arterial sistêmica, eritema malar, aftas, artrite, FAN+, com SLEDAI (systemic lupus erythematosus disease activity index) = 16 e anti-LPL = 144UA. Tratado com pulso de metilprednisolona e prednisona com melhora clínica e SLEDAI = 0 e redução do anti-LPL (109UA). Nova atividade com acometimento renal em abril de 2002, SLEDAI = 10 e aumento de anti-LPL (150UA). Iniciada pulsoterapia de ciclofosfamida e metilprednisolona com boa resposta, SLEDAI = 0 e diminuição de anti-LPL (77UA) até a sua total negativação acompanhando a remissão do quadro no ano de 2003. Caso 2: Mulher, 32 anos, com LES desde 1997. Em setembro de 2001 iniciou vasculite cutânea, febre e rash, SLEDAI = 10, anti-LPL = 80UA. Em janeiro de 2002, teve atividade renal e HAS...

INTRODUCTION: Systemic lupus erythematosus (SLE) is characterized by periods of clinical flares and remission that are followed by alterations of sera specific autoantibodies such as anti-dsDNA, present in 40 percent of the cases and strongly associated with renal involvement. Recently, there was a description of two subpopulations of anti-lipoprotein lipase antibodies (anti-LPL) in SLE: with and without anti-dsDNA activity. A possible relationship between these antibodies with inflammatory activity of SLE was not analyzed. OBJECTIVES: To evaluate longitudinally the association between anti-LPL with lupus activity in patients persistently negatives for anti-dsDNA antibodies. PATIENTS AND METHODS: Five SLE patients with persistently negative anti-dsDNA measured by ELISA and indirect immunofluorescence using crithidia luciliae and high titers of anti-LPL by ELISA (> 5 SD) were selected and followed for at least 2 years. RESULTS: Case 1: A 24-year-old male with SLE since 2001, presented with alveolar hemorrhage, proteinuria, systemic hypertension, malar rash, oral ulcers, polyarthritis, positive ANA, SLEDAI=16 and anti-LPL=144U. He was treated with intravenous (IV) methylprednisolone followed by prednisone and had an excellent response. SLEDAI=0, anti-LPL decreased to 109U. New renal flare in April 2002, SLEDAI=10 and a new increment of anti-LPL (150U). IV Cyclophosphamide and methylprednisolone were started and he achieved remission, SLEDAI=0 and a decrease of anti-LPL (77U) until become negative in 2003. Case 2: A 32-year-old female had SLE since 1997. In September 2001 began cutaneous vasculitis, fever and rash, SLEDAI=10, anti-LPL=80U. In January 2002, she had renal involvement and systemic hypertension, SLEDAI=8 and anti-LPL= 25U. She received corticosteroid and cyclophosphamide and improved. In 2003, she was asymptomatic, SLEDAI=2 and anti-LPL=12U. Case 3: A 39-year-old male has SLE since 1997. He was stable, under chloroquine use...

Auto-antibodies do not influence development of atherosclerotic plaques in rheumatoid arthritis.

BACKGROUND: Many questions remain unanswered about premature atherosclerosis in rheumatoid arthritis (RA). Besides inflammation, some studies have suggested the role of autoantibodies on its pathogenesis. OBJECTIVE: The aim of this study was to investigate the presence of antibodies against phospholipids, beta2-glycoprotein1 (beta2-gp1), lipoprotein lipase, and heat shock proteins (Hsp) in RA patients and to evaluate their possible association with subclinical carotid atherosclerosis. METHODS: Seventy-one RA patients and 53 age- and sex-matched controls were selected to perform anticardiolipin antibodies (aCL) (IgG and IgM), anti-beta2-gp1 (IgG, IgM, and IgA), anti-lipoprotein lipase (anti-LPL), anti-Hsp 60, and anti-Hsp 65 by ELISA tests. Intima-medial thickness (IMT) of common carotid and presence of plaques were assessed by high-resolution B-mode ultrasonography. Exclusion criteria were smoking, diabetes, and arterial hypertension. Lipoproteins, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fibrinogen levels, as well as health assessment questionnaire (HAQ) and disease activity score (DAS) 28 were also evaluated. RESULTS: Age (48.93+/-12.31 vs. 45.37+/-9.37 years; p=0.20) and body mass index (BMI) (p=0.69) were similar in RA and controls, as well as female gender (p=0.56). The mean IMT was similar between RA and controls (0.721+/-0.16 vs. 0.667+/-0.14 mm, p=0.07) but the frequency of plaques was higher in RA (14.1% vs. 1.9%; p=0.02). In RA patients, IMT measurements did not differ according to the presence or absence of these antibodies: IgG aCL (0.62+/-0.64 vs. 0.72+/-0.17 mm, p=0.24), IgM aCL (0.65+/-0.79 vs. 0.73+/-0.17 mm, p=0.33), anti-Hsp 60 (0.78+/-0.20 vs. 0.71+/-0.16 mm, p=0.27), anti-Hsp 65 (0.73+/-0.16 vs. 0.72+/-0.17 mm, p=0.77), IgG anti-beta2-gp1 (0.73+/-0.16 vs. 0.71+/-0.17 mm, p=0.72), and anti-CCP (0.71+/-0.16 vs. 0.76+/-0.20mm, p=0.36). In addition, IMT did not correlate with antibodies titers: IgG aCL (r=-0.09, p=0.47), IgM aCL (r=-0.15, p=0.21), anti-Hsp 60 (r=0.10, p=0.42), anti-Hsp 65 (r=0.05, p=0.69), IgG anti-beta2-gp1 (r=-0.07, p=0.57), IgM anti-beta2-gp1 (r=-0.05, p=0.69), IgA anti-beta2-gp1 (r=0.03, p=0.79), and anti-CCP (r=-0.07, p=0.57). RA patients with plaques had a significantly higher age compared to those without plaques (p=0.001), as well as higher mean IMT (p<0.001), total cholesterol (p=0.001), and LDL (p=0.003). CONCLUSIONS: In RA a clear association between all autoantibodies studied herein and increased IMT or presence of plaques was not observed. The great prevalence of carotid atherosclerosis in RA was related to age, total and LDL cholesterol, as identified in normal population.

Antibodies to ribosomal P proteins: a potential serologic marker for lupus membranous glomerulonephritis.

OBJECTIVE: To evaluate the relevance of antibodies to ribosomal P proteins (anti-P antibodies) in discriminating histopathologic patterns of lupus nephritis. METHODS: The study group comprised 81 consecutive patients with systemic lupus erythematosus who underwent renal biopsy and for whom frozen serum was available at the time of biopsy. All biopsy specimens were reviewed in a blinded manner, according to the 2004 criteria of the International Society of Nephrology and the Renal Pathology Society. Anti-P antibodies were detected by enzyme-linked immunosorbent assay (ELISA)/immunoblot analysis, and anti-double-stranded DNA (anti-dsDNA) was detected by indirect immunofluorescence/ELISA. RESULTS: Anti-P antibodies were detected in 18 patients (22%). The demographic and clinical features of patients with and those without anti-P antibodies were similar. Remarkably, analyses of biopsy specimens revealed that the frequency of anti-P antibodies in patients with class V lupus nephritis was higher than the frequency among patients with other classes of renal disease (72% versus 28%; P = 0.005). Accordingly, anti-P antibody-positive patients had a higher mean (+/-SD) proteinuria level compared with anti-P antibody-negative patients (6.4 +/- 4.8 versus 4.7 +/- 3.9 gm/dl; P = 0.046). Renal function was preserved in 6 of 7 patients who had both isolated anti-P antibodies and class V lupus nephritis. In contrast, anti-dsDNA was associated with proliferative-class lupus nephritis (P = 0.050) and higher creatinine levels (P = 0.014). Furthermore, 7 of 9 patients with isolated anti-P antibodies had class V lupus nephritis, and, more importantly, 5 of these 7 patients (71%) displayed a pure membranous pattern. Conversely, a tendency toward the predominance of class V lupus nephritis (67%) with concomitant proliferative lesions was observed when anti-P antibody was associated with anti-dsDNA. CONCLUSION: Our data introduce anti-P antibody as a novel serologic marker for membranous lupus nephritis and support the notion that the presence of isolated anti-P antibodies may discriminate patients with pure class V lupus nephritis, whereas the simultaneous presence of anti-dsDNA antibodies suggests class V disease with concomitant proliferative lesions.

The clinical spectrum of antinuclear antibodies associated with the nuclear dense fine speckled immunofluorescence pattern.

OBJECTIVE: Autoantibodies to lens epithelium-derived growth factor (LEDGF) depict a distinctive nuclear dense fine speckled (DFS) pattern in the indirect immunofluorescence antinuclear antibody assay (IIF-ANA). Definition of the clinical spectrum associated with anti-LEDGF antibodies has been evolving over the last decade. We investigated the frequency, clinical spectrum, and immunologic specificity of the DFS pattern in a general clinical laboratory routine. METHODS. All serum samples entered for IIF-ANA determination within a 2 year period were examined for the DFS pattern. Positive samples with consistent clinical information were studied further by IIF with isotype-specific conjugate and immunoblot analysis. RESULTS: Among 13,641 ANA-positive samples, 5081 (37%) presented the DFS pattern. Within a 6 month nested period, there were 650 samples with DFS pattern, and consistent clinical data were available for 81 of these. DFS reactivity was mainly due to IgG. Most samples (86%) presented titer > or = 1/640. Eighty of the 81 DFS samples reacted with a 75 kDa band that comigrated with the band elicited by the standard anti-LEDGF serum. Antibodies that were affinity-purified from the 75 kDa band reproduced the DFS pattern on IIF-ANA. The clinical spectrum associated with DFS reactivity included autoimmune diseases (39%) and an array of nonautoimmune conditions (61%). Among the autoimmune patients, over half presented evidence of autoimmune thyroiditis. CONCLUSION: Anti-LEDGF/p75 antibodies are a common finding among ANA-positive individuals with no evidence of rheumatic autoimmune disease, and should be regarded as a low specificity finding even when in moderate or high titer.