Late skin fibrosis in systemic sclerosis: a study from the EUSTAR cohort.

OBJECTIVES: The early trajectory of skin fibrosis provides insights into the disease course of systemic sclerosis (SSc) including mortality; however, little is known about late skin fibrosis. The aims of our study were to ascertain the prevalence and characteristics of late skin fibrosis in SSc. METHODS: We developed and tested three conceptual scenarios of late (>5 years after first non-RP feature) skin fibrosis including new worsening of skin disease, and failure to improve after worsening within 5-year window. We defined skin worsening as change in modified Rodnan skin score (mRSS) ≥5 units or ≥25%. Using strict inclusion criteria including complete mRSS, we identified 1,043 (out of 19 115) patients within the EUSTAR database for our analysis. We further restricted analysis within 887 (out of 1043) patients who had lcSSc or dcSSc at baseline. RESULTS: One-fifth of patients among the whole cohort (n = 208/1043, 19.9%) experienced mRSS worsening, including in patients with lcSSc or dcSSc at baseline (n = 193/887, 21.8%). This was largely due to new skin worsening after the 5-year window or failure to improve with worsening within the 5-year window. Patients with lower baseline mRSS and lcSSc were more likely to develop late skin fibrosis. Anti-Scl-70 was associated with progression from baseline lcSSc to dcSSc, and anticentromere was protective. CONCLUSIONS: Late skin fibrosis is not uncommon in SSc. We have identified different patterns relevant to clinical practice and trial design. Late skin fibrosis is a neglected manifestation of SSc and warrants further investigation including to determine clinical outcomes and optimal therapeutic strategy.

Digital pitting scars are associated with a severe disease course and death in systemic sclerosis: a study from the EUSTAR cohort.

OBJECTIVE: Digital pitting scars (DPS) are frequent, but little studied in SSc to date. METHODS: An analysis of SSc patients enrolled in the EUSTAR database. Primary objectives were to (i) examine DPS prevalence; (ii) examine whether DPS are associated with digital ulcers (DUs) and active digital ischaemia (DUs or gangrene); and (iii) describe other associations with DPS including internal organ complications. Secondary objectives were whether DPS are associated with (i) functional impairment; (ii) structural microvascular disease; and (iii) mortality. Descriptive statistics and parametric/non-parametric tests were used. Binary logistic regression was used to examine the association between DPS and DUs, active digital ischaemia and mortality. RESULTS: A total of 9671 patients were included with reported DPS at any time point (n = 4924) or 'never' DPS (n = 4747). The majority (86.9%) were female and mean age was 55.7 years. DPS were associated with longer disease and Raynaud's duration (both P ≤ 0.001). DPS were associated with interstitial lung disease, pulmonary hypertension, conduction blocks, telangiectases, calcinosis (all P ≤ 0.001) and joint synovitis (P = 0.021). Patients were more likely to have more severe capillaroscopic abnormality and greater hand functional impairment. Multivariable logistic regression analyses showed that DPS were associated (odds ratio) with DUs: 22.03 (19.51-24.87), active digital ischaemia: 6.30 (5.34-7.42) and death: 1.86 (1.48-2.36). CONCLUSION: DPS are associated with a severe disease course including death. The impact of DPS on hand function and ischaemia is significant. The presence of DPS should alert the clinician to a poor prognosis and need to optimize the therapeutic strategy.

Assessment of the Sources of Information by Patients With Rheumatic Diseases.

OBJECTIVE: The aim of this study was to ascertain the frequency of use, search intent (SI), level of accessibility, and degree of reliability of sources of information (SOIs) in rheumatology. METHODS: A survey among adult outpatients with rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and spondyloarthritis was conducted. They were asked if they had procured information from 12 selected SOIs during the past year. Search intent was defined as the source they would like to consult. Accessibility and reliability were assessed through 0-to-10 scales (minimum and maximum, respectively). RESULTS: Four hundred two patients were surveyed. They had consulted a median of 3 SOIs (interquartile range, 2-6) but described a higher SI: median of 5 SOIs (interquartile range 3-8); p = 0.001.The most consulted SOIs were the physician (83%), other patients (45%), and Facebook (36%). The main differences between SI and the searches actually performed were observed in community lectures by health care professionals (49%), scientific societies (48%), and associations of patients (27%); p < 0.001. These 3 sources showed low level of accessibility. Facebook, press, radio, and YouTube were the least reliable sources. CONCLUSIONS: Patients consulted a median of 3 SOIs but reported a significantly higher SI. Although patients demand more information, the request is leveled at SOIs with difficult accessibility but high reliability.

Description of the resources for rheumatology training and speciality certification and recertification requirements in Argentina.

The objective of the study was to analyse resources for rheumatology training, and speciality certification and recertification requirements in Argentina. Information was gathered regarding vacancies, entry requirements, duration and validity of the specialist degree in every residency and postgraduate course in adult rheumatology. The following aspects were analysed: monitoring authority, certification and recertification requirements, and mandatory recertification. Six out of 36 universities offer rheumatology postgraduate courses. Out of 65 vacancies, 36 (55%) are implemented by a National Public University in the Autonomous City of Buenos Aires (CABA), and 46 (70%) are in CABA. There are 32 vacancies for rheumatology residencies in 7 out of 24 districts, 16 of them (50%) in CABA. There are 2- to 3-year postgraduate courses; entry requirements range from 1-year experience in internal medicine to either complete residency or specialist degree in internal medicine. Training formats vary from full-time university residency to either university-based courses with part-time dedication in a rheumatology service without residency or non-university courses with part-time dedication. Not every specialist degree is automatically homologated in every jurisdiction. Provincial governments and colleges of physicians are the certification and recertification authorities; medical school was included in one district. Recertification is mandatory in only 8 districts; 40-50% of the process is achieved by merely practising as a rheumatologist. Most of the training resources are concentrated in CABA. Although there are various options, not all of them are automatically homologated. Recertification is not mandatory nationwide, and a significant part of the process involves practising as a rheumatologist.

Spanish Validation of the GEPARD Questionnaire for the Detection of Psoriatic Arthritis in Argentinian Patients with Psoriasis.

BACKGROUND/OBJECTIVE: Psoriatic arthritis (PsA) is preceded by psoriasis in approximately 80% of cases. Dermatologists are pivotal for early detection. It is important to have simple tools that allow the detection of PsA in patients with skin psoriasis. The aim of our study was to evaluate the performance of an adapted version of the GEPARD Questionnaire in Spanish in Argentinian patients with psoriasis. METHODS: This is a cross-sectional study. A new Spanish (Argentinian) (GEPARDa) translated version of the original questionnaire (German) was developed and then tested as a diagnostic tool in patients with psoriasis, PsA, osteoarthritis associated to psoriasis, and osteoarthritis, all evaluated by rheumatologists who used the CASPAR criteria. RESULTS: Eighty-three patients were included (55 [66.3%] women with a mean age of 50.7 years [SD 6.3]). Forty-four patients had PsA (29 [34.9%] patients had previous diagnosis of PsA, and 15 [18%] were newly diagnosed after referral by their dermatologists), and 39 patients were without PsA (18 [21.6%] patients had psoriasis without articular involvement, 6 [7.22%] had psoriasis associated with osteoarthritis, and 15 [18%] had osteoarthritis). An area under the curve of 0.9554 (SD 0.01; 95% CI 0.91-0.99) was calculated considering the CASPAR criteria as the gold standard. With a cutoff of ≥6 the questionnaire showed a sensitivity of 88.64%, a specificity of 89.74%, a positive likelihood ratio of 8.6, and a negative likelihood ratio of 0.12. CONCLUSIONS: The GEPARDa version has proven to be a diagnostic tool with excellent performance so that it can be considered a valid tool for the detection of PsA in Argentinian patients.

Use of systemic glucocorticoids in patients with psoriatic arthritis by Argentinian and other Latin-American rheumatologists.

To analyse the administration of systemic glucocorticoids (SGC) to patients with Psoriatic arthritis (PsA). Online, anonymous, multiple-choice, closed-ended survey on SGC use in PsA, dose, duration of therapy, and the reason for administration. One hundred and twenty rheumatologists from Argentina (ARG) and 75 from other countries in Latin-America (LAT) completed the survey. Only 6% of the respondents indicated that they did not prescribe SGC, and 65% claimed that they administered them to less than 10% of their patients. Among those physicians who used SGC, 71% prescribed between 5 and 10 mg/day of prednisone, and only 5% over 10 mg/day. Seventy-three percent of the respondents administered SGC for less than 3 months, and 93% associated them with DMARDs, Biological Therapy (BT), or DMARDs plus BT. Clinical indications for SGC were (more than one option was possible): peripheral arthritis (79%), dactylitis (23%), enthesitis (20%), cutaneous involvement (11%), and axial involvement (8%). Thirty-four percent of ARG physicians versus 21% of LAT used SGC in over 10% of their patients (p 0.07) while 76.5% of ARG versus 59% of LAT administered doses higher than 5 mg/day of prednisone (p 0.01). SGC were indicated by most of the rheumatologists surveyed, but only to a reduced number of patients with PsA, at low doses, for short periods of time, associated with DMARDs/BT, and with the aim of treating peripheral joint manifestations. Argentinian physicians tended to prescribe SGC to more patients and at slightly higher doses.

Lung Ultrasound as a Screening Method for Interstitial Lung Disease in Patients With Systemic Sclerosis.

BACKGROUND: Patients with systemic sclerosis (SSc) undergo chest radiographs and high-resolution computed tomography (HRCT) of the thorax both for interstitial lung disease (ILD) detection and for disease progression monitoring. OBJECTIVE: The aim of this study was to assess whether lung ultrasound (LUS) is a useful screening tool for ILD in patients with SSc in comparison with HRCT. METHODS: This was a longitudinal cohort study carried out from December 2015 to April 2016. An LUS was performed to examine B-lines in 67 consecutive patients who met the 2013 American College of Rheumatology/European League Against Rheumatism classification criteria for SSc and had a previous HRCT. B-lines were quantified and classified according to the score modified from Picano. Severity and extent of lung involvement on the HRCT were determined by means of the Warrick score. RESULTS: Twenty-nine patients had both abnormal HRCT (Warrick score >7) and abnormal LUS, 2 had a mild score (6-15 B-lines), and 27 had either moderate or severe scores (≥16 B-lines). Of the 38 patients with negative HRCT, 25 presented some degree of lung involvement on the LUS. Thus, LUS has a sensitivity of 100% and a specificity of 34%. Receiver operating characteristic curve analysis showed the analytic relation between the number of B-lines and the presence of ILD on the HRCT (area under the curve, 0.80; 95% confidence interval, 0.69-0.90). CONCLUSIONS: Lung ultrasound may be a method to detect abnormal lung findings in a noninvasive manner in patients with SSc. Because of its high sensitivity, a low score almost rules out the need for an HRCT.

Analysis of the data on pregnancy and lactation provided by patient information leaflets of anti-rheumatic drugs in Argentina.

To analyse the level of consistency and updating of the information on pregnancy and lactation provided by patient information leaflets (PILs) of the antirheumatic drugs approved in Argentina. Inconsistencies between the 2016 EULAR Task Force recommendations on the use of anti-rheumatic drugs during pregnancy and lactation and the information provided by PILs of the same drugs approved in Argentina were analysed along with inconsistencies within the PILs of different registered trademarks of these drugs. Eighty-eight PILs of 32 drugs were analysed. Out of the 88 PILs, 50% presented information inconsistencies as to pregnancy. Medications comprised in this group were: hydroxychloroquine, sulfasalazine, azathioprine, tacrolimus, cyclosporine, NSAIDs (during the first two trimesters), celecoxib, some glucocorticoids, colchicine, and some anti-TNF drugs (etanercept, adalimumab and infliximab) during part of the pregnancy. As for lactation, 56% had information inconsistencies. Medications encompassed in this group were: hydroxychloroquine, chloroquine, sulfasalazine, azathioprine, tacrolimus, cyclosporine, NSAIDs, celecoxib, meprednisone, prednisone, colchicine, and anti-TNF drugs. Out of 17 drugs that had more than one registered trademark, information inconsistencies on pregnancy were found in the PILs of sulfasalazine, diclofenac, ibuprofen and methylprednisolone. Concerning lactation, inconsistencies were present in the PILs of hydroxychloroquine, sulfasalazine, diclofenac, ibuprofen, meprednisone, and colchicine. At least half of the PILs of anti-rheumatic drugs analysed in this study had information inconsistencies on pregnancy and lactation. This is a serious state of affairs because the consensual decision-making process between patient and professional may be compromised, which, in turn, may give rise to medical-legal issues.

Intercentre variance in patient reported outcomes is lower than objective rheumatoid arthritis activity measures: a cross-sectional study.

Objective: To assess intercentre variability in the ACR core set measures, DAS28 based on three variables (DAS28v3) and Routine Assessment of Patient Index Data 3 in a multinational study. Methods: Seven thousand and twenty-three patients were recruited (84 centres; 30 countries) using a standard protocol in the Quantitative Standard Monitoring of Patients with RA study. Analysis of variance (ANOVA) and mixed-effect analysis of covariance models were used to model the relationship between study centre and different patient-reported and physician-reported RA activity measures. These models were built to adjust for the remaining ACR core set measure (for each ACR core set measure or each composite index), socio-demographics and medical characteristics. ANOVA and analysis of covariance models yielded similar results, and ANOVA tables were used to present variance attributable to recruiting centre. Results: The proportion of variances attributable to recruiting centre was lower for patient reported outcomes (PROs: pain, HAQ, patient global) compared with objective measures (joint counts, ESR, physician global) in all models. In the full model, variance in PROs attributable to recruiting centre ranged from 1.53% for patient global to 3.71% for HAQ compared with objective measures that ranged from 5.92% for physician global to 9.25% for ESR; and was lower for Routine Assessment of Patient Index Data 3 (2.6%) compared with DAS28v3 (11.75%). Conclusion: Intercentre variability in PROs is lower than objective measures of RA activity demonstrating that PROs may be more comparable across centres, and the need for standardization of objective measures.

Breastfeeding initiation, duration, and reasons for weaning in patients with systemic lupus erythematosus.

To assess breastfeeding in patients with systemic lupus erythematosus (SLE), a cross-sectional study of patients with SLE compared to a non-SLE sample was performed. Patients who had pregnancies subsequent to their diagnosis of SLE and who were followed up in the hospital were interviewed. The group of non-SLE mothers consisted of patients who had no known rheumatic disease at the time of their pregnancy, and who were approached at the hospital paediatrics service waiting room. Thirty-six pregnancies in 31 patients with SLE and the same number of non-SLE mothers were studied. The number of SLE patients who did not initiate breastfeeding was higher than that of non-SLE mothers (19.4 vs 5.6%, respectively; p 0.07). The average duration of breastfeeding in SLE patients was 6 months (SD 6 months) versus 12 months (SD 8 months) in non-SLE mothers (log rank p: 0.003). Fifty-three percent of the non-SLE mothers indicated no particular reason for weaning, and considered that they had nursed their children a suitable amount of time. Conversely, SLE patients often set weaning in motion on the grounds that they had been placed on medication (41%). However, when the treatment was analysed, in 6 out of 12 cases, it consisted of low doses of either corticosteroids or hydroxychloroquine. Patients with SLE showed reduced rates of initiating breastfeeding. They also showed reduced duration of breastfeeding, and the reason for cessation was frequently cited to be therapies which were actually of low risk. Breastfeeding duration could be optimised by improving the level of information provided to patients.

[Cognitive dysfunction in systemic lupus erythematosus in relation to disease activity and damage]. / Disfunción cognitiva en lupus eritematoso sistémico y su asociación con actividad y daño.

Systemic lupus erythematosus (SLE) is a rheumatic disease, which during its evolution may present neurocognitive dysfunction with fronto-subcortical compromise. However, there is no enough published evidence regarding the relationship between cognitive dysfunction and SLE activity and SLE induced damage. The objective of the study was to analyze this association. We designed an observational cross-sectional study including 84 patients with SLE. We used the SLEDAI index to evaluate activity and the SLICC index to evaluate cumulative damage. We used neuropsychological tests to assess the presence of cognitive symptoms, global cognitive function, verbal and visual memory, visual-construction, semantic verbal fluency, processing speed and working memory. Scores more than 1.5 standard deviations below adjusted normal values were considered as cognitive dysfunction. We observed a statistically significant association between the higher value of SLEDAI and working memory impairment and a higher value of SLICC and viso-construction and semantic verbal fluency impairment. The association observed in SLE patients between disease activity or damage and some cognitive domains may be involving different pathophysiological brain mechanisms of different areas with different degrees of severity and vulnerability.

The non-silent epidemic: low back pain as a primary cause of hospitalisation.

Low back pain (LBP) is the most common cause of pain in adults and the second health condition that prompts patients to seek ambulatory medical care visits. To analyse the impact of LBP on hospitalisations in healthcare facilities within the official subsector in Argentina between 2006 and 2010. Discharges in which the original diagnosis had been either adult LBP or lumbosciatica were assessed. The data comprised age, gender, province of residence, average length of stay (LOS) in the hospital, intra-hospital death, and the Provincial Human Development Index (PHDI). 17,859 discharges had an original diagnosis of LBP and 10,948 of lumbosciatica, which jointly accounted for 18.7 % of all the discharges documented for Diseases of Osteomuscular System and Connective Tissue (DOMS). Hospital discharges of female patients represented 53.7 %. The average age upon admission was 47.7 years in men versus 47.9 in women. The average LOS was slightly higher in men (4.2 vs. 3.8 days, p 0.01). In provinces with a PHDI below the national average, a surgical procedure was performed in 3.1 % of the discharges versus 4.1 % in the provinces with a PHDI above the national average (p < 0.001). LBP was the most frequent cause of hospitalisation due to DOMS. It occurred with a slightly higher frequency in women and prompted short hospitalisations. A surgical procedure was carried out during hospitalisation in very few cases, but the percentage of surgeries during hospitalisation was higher in provinces with a PHDI above the national average.

The association of fatigue, comorbidity burden, disease activity, disability and gross domestic product in patients with rheumatoid arthritis. Results from 34 countries participating in the Quest-RA program.

OBJECTIVES: The aim is to assess the prevalence of comorbidities and to further analyse to which degree fatigue can be explained by comorbidity burden, disease activity, disability and gross domestic product (GDP) in patients with rheumatoid arthritis (RA). METHODS: Nine thousands eight hundred seventy-four patients from 34 countries, 16 with high GDP (>24.000 US dollars [USD] per capita) and 18 low-GDP countries (<24.000 USD) participated in the Quantitative Standard monitoring of Patients with RA (QUEST-RA) study. The prevalence of 31 comorbid conditions, fatigue (0-10 cm visual analogue scale [VAS] [10=worst]), disease activity in 28 joints (DAS28), and physical disability (Health Assessment Questionnaire score [HAQ]) were assessed. Univariate and multivariate linear regression analyses were performed to assess the association between fatigue and comorbidities, disease activity, disability and GDP. RESULTS: Overall, patients reported a median of 2 comorbid conditions of which hypertension (31.5%), osteoporosis (17.6%), osteoarthritis (15.5%) and hyperlipidaemia (14.2%) were the most prevalent. The majority of comorbidities were more common in high-GDP countries. The median fatigue score was 4.4 (4.8 in low-GDP countries and 3.8 in high-GDP countries, p<0.001). In low-GDP countries 25.4% of the patients had a high level of fatigue (>6.6) compared with 23.0% in high-GDP countries (p<0.001). In univariate analysis, fatigue increased with increasing number of comorbidities, disease activity and disability in both high- and low-GDP countries. In multivariate analysis of all countries, these 3 variables explained 29.4% of the variability, whereas GDP was not significant. CONCLUSIONS: Fatigue is a widespread problem associated with high comorbidity burden, disease activity and disability regardless of GDP.

Speciality training in rheumatology: Promotion, repetition and dropout rates in the city of Buenos Aires.

OBJECTIVES: To evaluate the trajectory of students enrolled in the specialty training in rheumatology. METHODS: Retrospective analysis (2009-2016). Promotion, repetition, and dropout rates were determined. Analysis was performed to define variables associated with academic success. RESULTS: Out of 119 students, the actual promotion rate was 66.4%, 11.8% failed an exam (at least) and completed the course after the stipulated time, and the dropout rate was 7.6%. Among residents, the promotion rate was 82.5% vs. 48.2% among the rest (p < 0.001), the lagging students' repetition rate was 3.2% vs. 21.4% among the rest (p 0.005), and the dropout rate was 3.2% vs. 12.5% among the rest (p = 0.06). A higher average score in medical school increased the chances of success in the postgraduate programme (OR 3.41 CI 95% 2.0-6.4; p < 0.001). CONCLUSIONS: The residency was associated with higher rates of academic success in postgraduate studies. The average score in medical school can help identify students at risk of failure.

The development of candidate composite disease activity and responder indices for psoriatic arthritis (GRACE project).

OBJECTIVE: To develop new composite disease activity indices for psoriatic arthritis (PsA). METHODS: Data from routine clinic visits at multiple centres were collected in a systematic manner. Data included all domains identified as important in randomised controlled trials in PsA. Decisions to change treatment were used as surrogates for high disease activity. New indices were developed by multiple linear regression (psoriatic arthritis disease activity score: PASDAS) and empirically, utilising physician-defined cut-offs for disease activity (arithmetic mean of desirability functions: AMDF). These were compared with existing composite measures: Composite Psoriatic arthritis Disease Activity Index (CPDAI), Disease Activity for PSoriatic Arthritis (DAPSA), and Disease Activity Score for rheumatoid arthritis (DAS28). RESULTS: 161/503 (32%) subjects had treatment changes. Although all measures performed well, compared with existing indices, PASDAS was better able to discriminate between high and low disease activity (area under receiver operating curves (ROC)) curve with 95% CI: PASDAS 0.773 (0.723, 0.822); AMDF 0.730 (0.680, 0.780); CPDAI 0.719 (0.668, 0.770); DAPSA 0.710 (0.654, 0.766); DAS28 0.736 (0.680, 0.792). All measures were able to discriminate between disease activity states in patients with oligoarthritis, although area under the receiver operating curves (AUC) were generally smaller. In patients with severe skin disease (psoriasis area and severity index>10) both nonparametric and AUC curve statistics were nonsignificant for all measures. CONCLUSIONS: Two new composite measures to assess disease activity in PsA have been developed. Further testing in other datasets, including comparison with existing measures, is required to validate these instruments.

Publication outcomes of abstracts presented at the Argentine Congress of Rheumatology.

OBJECTIVE: To analyse the outcome of scientific abstracts submitted to the Argentine Congress of Rheumatology (ACOR) in 2000, 2005, 2010, and 2015. METHODS: Every abstract submitted to the ACOR was analysed. The number of these manuscripts published was determined through Google Scholar and PubMed searches. The impact of the scientific journals was established through the SCImago Journal (SJR) indicator. RESULTS: Considering the 727 abstracts evaluated, 10.2% of the articles were found in journals indexed by Google Scholar, and 6.6% in PubMed: 4.7% were published in 2000, 9.4% in 2005, 14.6% in 2010, and 11.9% in 2015 (Log Rank test 0.008), with a statistically significant increase between 2010 and 2015 compared to 2000 (HR 3.3; 95% CI 1.5-7; p 0.002 and HR 2.9; CI 1.4-6.3; p 0.005 respectively). The median SJR of the journals was 0.46 and 67.6% had SJR available. CONCLUSIONS: The publication rate was low, and only a few articles were published in the most prestigious journals within the speciality.

Patient's global assessment of disease activity and patient's assessment of general health for rheumatoid arthritis activity assessment: are they equivalent?

OBJECTIVES: To assess (A) determinants of patient's global assessment of disease activity (PTGL) and patient's assessment of general health (GH) scores of rheumatoid arthritis (RA) patients; (B) whether they are equivalent as individual variables; and (C) whether they may be used interchangeably in calculating common RA activity assessment composite indices. METHODS: Data of 7023 patients from 30 countries in the Quantitative Standard Monitoring of Patients with RA (QUEST-RA) was analysed. PTGL and GH determinants were assessed by mixed-effects analyses of covariance models. PTGL and GH equivalence was determined by Bland-Altman 95% limits of agreement (BALOA) and Lin's coefficient of concordance (LCC). Concordance between PTGL and GH based Disease Activity Score 28 (DAS28), Clinical Disease Activity Index (CDAI) and Routine Assessment of Patient Index Data 3 (RAPID3) indices were calculated using LCC, and the level of agreement in classifying RA activity in four states (remission, low, moderate, high) using κ statistics. RESULTS: Significant differences in relative and absolute contribution of RA and non-RA related variables in PTGL and GH ratings were noted. LCC of 0.64 and BALOA of -4.41 to 4.54 showed that PTGL and GH are not equivalent. There was excellent concordance (LCC 0.95-0.99) for PTGL and GH based DAS28, CDAI and RAPID3 indices, and >80% absolute agreement (κ statistics 0.75-0.84) in RA activity state classification for all three indices. CONCLUSIONS: PTGL and GH ratings differ in their determinants. Although they are individually not equivalent, they may be used interchangeably for calculating composite indices for RA activity assessment.

Drugs Recommended in Adult Rheumatic Diseases, But Considered for Off-Label Use in Argentina.

BACKGROUND: Off-label (OL) drug use is the prescription of a drug for indications other than those authorised in its technical datasheet. The objective of this study was to identify drugs recommended in rheumatology but considered for off-label use in Argentina. METHODS: A list of medications for certain selected rheumatic conditions was compiled. A drug was considered recommended if it was endorsed by a) at least one Argentine or Pan-American treatment guideline or consensus, or b) two international treatment guidelines, or c) one international treatment guideline and one selected textbook. Approval of these drugs for any condition in Argentina until December 31st, 2018 was explored, and medicines were divided into those with on-label indications and those considered for OL use. RESULTS: One hundred and thirty-six medications were analysed in 13 clinical conditions. Sixty-seven OL recommendations (49%) were found, and several drugs had more than one. All the conditions included the recommendation of at least 1 OL drug except osteoporosis and rheumatoid arthritis. The frequency of OL recommendations for the following conditions was 100%: calcium pyrophosphate dihydrate crystal deposition disease, polymyalgia rheumatica, Sjögren syndrome, and systemic sclerosis. The drugs with the highest number of OL recommendations were methotrexate (in 7 conditions), and glucocorticoids and mycophenolate (in 4). There were 2 OL recommendations for rituximab and 1 for abatacept. CONCLUSIONS: Almost all the rheumatic disorders analysed involved the recommendation of at least 1 OL medication, and in 4 conditions all the recommendations were OL. Most OL drugs recommended in rheumatology are neither biological nor small-molecule therapies.

The effects of tibolone in older postmenopausal women.

BACKGROUND: Tibolone has estrogenic, progestogenic, and androgenic effects. Although tibolone prevents bone loss, its effects on fractures, breast cancer, and cardiovascular disease are uncertain. METHODS: In this randomized study, we assigned 4538 women, who were between the ages of 60 and 85 years and had a bone mineral density T score of -2.5 or less at the hip or spine or a T score of -2.0 or less and radiologic evidence of a vertebral fracture, to receive once-daily tibolone (at a dose of 1.25 mg) or placebo. Annual spine radiographs were used to assess for vertebral fracture. Rates of cardiovascular events and breast cancer were adjudicated by expert panels. RESULTS: During a median of 34 months of treatment, the tibolone group, as compared with the placebo group, had a decreased risk of vertebral fracture, with 70 cases versus 126 cases per 1000 person-years (relative hazard, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001), and a decreased risk of nonvertebral fracture, with 122 cases versus 166 cases per 1000 person-years (relative hazard, 0.74; 95% CI, 0.58 to 0.93; P=0.01). The tibolone group also had a decreased risk of invasive breast cancer (relative hazard, 0.32; 95% CI, 0.13 to 0.80; P=0.02) and colon cancer (relative hazard, 0.31; 95% CI, 0.10 to 0.96; P=0.04). However, the tibolone group had an increased risk of stroke (relative hazard, 2.19; 95% CI, 1.14 to 4.23; P=0.02), for which the study was stopped in February 2006 at the recommendation of the data and safety monitoring board. There were no significant differences in the risk of either coronary heart disease or venous thromboembolism between the two groups. CONCLUSIONS: Tibolone reduced the risk of fracture and breast cancer and possibly colon cancer but increased the risk of stroke in older women with osteoporosis. (ClinicalTrials.gov number, NCT00519857.)

Drugs Recommended in Adult Rheumatic Diseases, But Considered for Off-Label Use in Argentina.

BACKGROUND: Off-label (OL) drug use is the prescription of a drug for indications other than those authorised in its technical datasheet. The objective of this study was to identify drugs recommended in rheumatology but considered for off-label use in Argentina. METHODS: A list of medications for certain selected rheumatic conditions was compiled. A drug was considered recommended if it was endorsed by a) at least one Argentine or Pan-American treatment guideline or consensus, or b) two international treatment guidelines, or c) one international treatment guideline and one selected textbook. Approval of these drugs for any condition in Argentina until December 31st, 2018 was explored, and medicines were divided into those with on-label indications and those considered for OL use. RESULTS: One hundred and thirty-six medications were analysed in 13 clinical conditions. Sixty-seven OL recommendations (49%) were found, and several drugs had more than one. All the conditions included the recommendation of at least 1 OL drug except osteoporosis and rheumatoid arthritis. The frequency of OL recommendations for the following conditions was 100%: calcium pyrophosphate dihydrate crystal deposition disease, polymyalgia rheumatica, Sjögren syndrome, and systemic sclerosis. The drugs with the highest number of OL recommendations were methotrexate (in 7 conditions), and glucocorticoids and mycophenolate (in 4). There were 2 OL recommendations for rituximab and 1 for abatacept. CONCLUSIONS: Almost all the rheumatic disorders analysed involved the recommendation of at least 1 OL medication, and in 4 conditions all the recommendations were OL. Most OL drugs recommended in rheumatology are neither biological nor small-molecule therapies.