No es el mismo pero ¿es igual? Cycling de agentes biológicos en artritis reumatoide. Experiencia en el Instituto Mexicano del Seguro Social / Not the same, but is it the same? Cycling of biologic agents in rheumatoid arthritis. Experience in the Instituto Mexicano del Seguro Social

Introducción: Los datos disponibles para los biocomparables comercializados actualmente no son concluyentes con respecto al potencial impacto del cambio por razones no médicas sobre la eficacia, la seguridad y la inmunogenicidad en los pacientes. En el futuro se expandirán las opciones de tratamiento biológico, biocomparable, no bio-comparables y otros de síntesis química, por lo que es importante conocer cómo se comporta la persistencia al tratamiento tras un cambio por razón no médica, que ya ocurre como un hecho habitual en los servicios médicos de seguridad social en México, ya que esto nos ayudará a entender los mejores estándares de tratamiento para pacientes con enfermedades inmunomediadas crónicas. Objetivos: El objetivo primario fue evaluar el impacto del cambio por razón no médica en pacientes con artritis reumatoide (AR) estables tratados con biológico innovador sobre la persistencia en el tratamiento, después de cambiar a un biocomparable o a un no biocomparable, en relación con los pacientes que continúan con el biológico innovador. Diseño del estudio: Estudio observacional (no intervencionista) de cohortes emparejado donde se comparó una cohorte histórica obtenida por la revisión de historias médicas de pacientes estables que no fueron cambiados de tratamiento por al menos 6meses, con dos cohortes de pacientes que fueron cambiados de tratamiento por razones no médicas a otro fármaco con la misma diana terapéutica (cycling). Resultados: Se incluyeron 264 pacientes con diagnóstico de AR (ACR/EULAR, 2010): 132 pacientes que fueron cambiados de tratamiento por razones no médicas por un fármaco de mecanismo similar de acción y 132 pacientes que no fueron cambiados de tratamiento. De los 264 pacientes participantes en el estudio, 230 pacientes (87,1%) corresponden al sexo femenino. El promedio de edad fue de 53,9años, la edad mínima 16años y la máxima 84 años. (AU)

Introduction: Available data for biocomparable drugs are not enough to make clear decisions with respect to the potential consequences of a change for non-medical reasons in efficacy, security and inmunogenicity in patients. In the near future, options on biological treatments, biocomparable drugs, non biocomparable drugs and new chemical synthesis options will grow. Therefore, it is important to know how patients behave in persistence of treatment after a change for non-medical reasons, which already happens on a regular basis in social security institutions in Mexico. This information will help us to better understand the standard of treatment for patients with chronic immunomediated conditions. Objective: The primary objective was to measure the impact of change for non-medical reasons in patients with rheumatoid arthritis (RA) treated with an innovative biological on persistence of treatment after changing to a biocomparable drug or a non-biocomparable drug, compared with those patients staying with the innovative biological. Study design: This is an observational study (non-interventionist) of paired cohorts, where an historic cohort obtained by review of clinical records of stable patients in which no modifications to treatment were made for at least six months is compared with two cohorts of patients whose treatments were switched to another treatment with the same therapeutic mechanism for-non-medical reasons (cycling). Results: We included 264 RA patients (ACR/EULAR, 2010); 132 were switched for non-medical reasons, and 132 were not switched. Two-hundred and thirty (87.1%) were female. Average age was 53.9years, ranging from 16 to 84years. Two-hundred and sixty-three patients were Latino (99.6%); one was Caucasian.(AU)

Not the same, but is it the same? Cycling of biologic agents in rheumatoid arthritis. Experience in the Instituto Mexicano del Seguro Social.

INTRODUCTION: Available data for biocomparable drugs are not enough to make clear decisions with respect to the potential consequences of a change for non-medical reasons in efficacy, security and inmunogenicity in patients. In the near future, options on biological treatments, biocomparable drugs, non biocomparable drugs and new chemical synthesis options will grow. Therefore, it is important to know how patients behave in persistence of treatment after a change for non- medical reasons, which already happens on a regular basis in social security institutions in Mexico. This information will help us to better understand the standard of treatment for patients with chronic immunomediated conditions. OBJECTIVE: The primary objective was to measure the impact of change for non-medical reasons in patients with rheumatoid arthritis (RA) treated with an innovative biological on persistence of treatment after changing to a biocomparable drug or a non-biocomparable drug, compared with those patients staying with the innovative biological. STUDY DESIGN: This is an observational study (non-interventionist) of paired cohorts, where an historic cohort obtained by review of clinical records of stable patients in which no modifications to treatment were made for at least six months is compared with two cohorts of patients whose treatments were switched to another treatment with the same therapeutic mechanism for-non-medical reasons (cycling). RESULTS: We included 264 RA patients (ACR/EULAR, 2010); 132 were switched for non-medical reasons, and 132 were not switched. Two-hundred and thirty (87.1%) were female. Average age was 53.9 years, ranging from 16 to 84 years. Two-hundred and sixty-three patients were Latino (99.6%); one was Caucasian. Persistence of treatment 12 months after the change was 84.8% (85.8% in Enbrel/Infinitam, 78.9% for Remicade/Remsima). No statistical difference was found with respect to RA clinical activity measured by DAS28 12 months after the switch (P > .05). In the 134 switched patients, 20 discontinued the new treatment due to lack of efficacy of the new drug and were changed to a different drug with a different biologic target. Although no differences were found in the cohorts of switched patients with respect to DAS 28 after 12 months of use, we did find differences in the frequency of adverse events. Forty-two patients had an adverse event in the drug switch cohorts: 33 in the Enbrel-Infinitam group and 9 in the Remicade-Remsima group. CONCLUSIONS: The persistence of treatment after switching from an innovative drug to a biocomparable or a non- biocomparable in RA patients did not show statistically significative differences in our cohorts, but we did find a higher number of adverse events when comparing those who were changed with those who continued on an innovative drug. Twenty patients in the switch groups had to receive a new drug with a different biological target due to lack of efficacy of the switched drug.

Not the same, but ¿is it the same? Cycling of biologic agents in rheumatoid arthritis. Experience in the Instituto Mexicano del Seguro Social. / No es el mismo pero ¿es igual? Cycling de agentes biológicos en artritis reumatoide. Experiencia en el Instituto Mexicano del Seguro Social.

INTRODUCTION: Available data for biocomparable drugs are not enough to make clear decisions with respect to the potential consequences of a change for non-medical reasons in efficacy, security and inmunogenicity in patients. In the near future, options on biological treatments, biocomparable drugs, non biocomparable drugs and new chemical synthesis options will grow. Therefore, it is important to know how patients behave in persistence of treatment after a change for non-medical reasons, which already happens on a regular basis in social security institutions in Mexico. This information will help us to better understand the standard of treatment for patients with chronic immunomediated conditions. OBJECTIVE: The primary objective was to measure the impact of change for non-medical reasons in patients with rheumatoid arthritis (RA) treated with an innovative biological on persistence of treatment after changing to a biocomparable drug or a non-biocomparable drug, compared with those patients staying with the innovative biological. STUDY DESIGN: This is an observational study (non-interventionist) of paired cohorts, where an historic cohort obtained by review of clinical records of stable patients in which no modifications to treatment were made for at least six months is compared with two cohorts of patients whose treatments were switched to another treatment with the same therapeutic mechanism for-non-medical reasons (cycling). RESULTS: We included 264 RA patients (ACR/EULAR, 2010); 132 were switched for non-medical reasons, and 132 were not switched. Two-hundred and thirty (87.1%) were female. Average age was 53.9years, ranging from 16 to 84years. Two-hundred and sixty-three patients were Latino (99.6%); one was Caucasian. Persistence of treatment 12months after the change was 84.8% (85.8% in Enbrel/Infinitam, 78.9% for Remicade/Remsima). No statistical difference was found with respect to RA clinical activity measured by DAS28 12months after the switch (P>.05). In the 134 switched patients, 20 discontinued the new treatment due to lack of efficacy of the new drug and were changed to a different drug with a different biologic target. Although no differences were found in the cohorts of switched patients with respect to DAS28 after 12months of use, we did find differences in the frequency of adverse events. Forty-two patients had an adverse event in the drug switch cohorts: 33 in the Enbrel-Infinitam group and 9 in the Remicade-Remsima group. CONCLUSIONS: The persistence of treatment after switching from an innovative drug to a biocomparable or a non-biocomparable in RA patients did not show statistically significative differences in our cohorts, but we did find a higher number of adverse events when comparing those who were changed with those who continued on an innovative drug. Twenty patients in the switch groups had to receive a new drug with a different biological target due to lack of efficacy of the switched drug.

Cross-cultural adaptation and validation of the Gait, Arms, Legs, Spine locomotor screening test for detecting musculoskeletal disorders in Mexican adults.

AIM: Developed in the United Kingdom, the Gait, Arms, Legs and Spine (GALS) sensitive screening test enables doctors to examine joints and positions at rest and during motion. Therefore, patients with an early diagnosis for musculoskeletal (MSK) disorders, can enjoy a better quality of life than those diagnosed at a later stage. The objective was to adapt and validate a Mexican-Spanish version of the GALS measurement instrument for MSK disorders in Mexican adults. MATERIALS AND METHODS: We conducted a cross-sectional diagnostic test study among 18- 60-year-old adults in a hospital in the city of Guadalajara, Mexico. Based on international guidelines, we divided our work into 2 phases: first, we developed and adapted a cross-cultural, Mexican-Spanish version of the GALS; second, we validated the instrument as a diagnostic test among Mexican patients. RESULTS: The adapted version yielded the following scores as a measurement instrument: 0.92 under Cronbach's alpha, 0.695 (95% CI, 0.592-0.797) in the kappa index, 98.2% (95% CI, 90.3%-100%) in sensitivity, 80.6% (95% CI, 72.9%-86.9%) in specificity, and 5.06 for positive likelihood ratio. It also covered an area of 0.89 (95% CI, 0.85-0.93) under the receiver operating characteristic curve. CONCLUSIONS: The GALS diagnostic test proved valid for detecting MSK disorders among Mexican adults. It can be used by specialized physicians, family doctors, general practitioners and even physicians in training.

Trends of Informed Consent forms for industry-sponsored clinical trials in rheumatology over a 17-year period: Readability, and assessment of patients' health literacy and perceptions.

OBJECTIVE: To assess trends in the length and readability of informed consent forms (ICFs) for industry-sponsored multinational clinical trials (RCTs) in rheumatology over a 17-year period. Additionally, to assess the health literacy (HL) and perceptions of ICFs among participants of current RCTs. METHODS: The readability of ICFs conducted at an outpatient rheumatology clinic between 1999 and 2016 were assessed using the INFLESZ scale. Patients' HL was assessed using SALHSA-50 and STOFHLA. Patient opinions were assessed using a self-reported, in-office questionnaire with an independent patient sample who had signed an ICF in the past 6 months. RESULTS: Thirty-nine ICFs about 22 drugs from 13 pharmaceutical companies were analyzed. The global mean readability was 57 ± 3 (95% CI: 56-58), and all ICFs were categorized as either "somewhat difficult to read" or "average." Readability remained at these levels without significant changes from 1999 to 2016. The mean length of the ICFs written between 1999 and 2005 was 13 ± 5 pages, with a significant increase thereafter (mean 22 ± 8 pages, p = 0.004). Depending on the instrument, of 95 patients participating in the HL assessment, between 18% and 44% had limited HL. Of 90 patients participating in the perceptions questionnaire, 84% reported understanding the ICF well. However, 2-57% misunderstood basic concepts, including the study drug name and placebo. CONCLUSIONS: The disparity between the readability of ICFs with patients' HL and their comprehension of ICFs continues, even after decades of attempts of regulatory agencies and numerous published suggestions.

Autoantibodies in prediction of the development of rheumatoid arthritis among healthy relatives of patients with the disease.

OBJECTIVE: Although blood bank-based studies have shown that rheumatoid arthritis (RA)-related autoantibodies are present before the onset of RA, information on their positive predictive value (PPV) for development of RA in healthy individuals is scarce. This study was undertaken to assess the 5-year PPV of serum IgM rheumatoid factor (IgM-RF) and anti-cyclic citrullinated peptide (anti-CCP) for the development of RA among healthy relatives of patients with RA. METHODS: Healthy relatives of RA patients were invited to participate in a cohort study. At baseline, information on participants' medical history was obtained, and serum levels of IgM-RF and anti-CCP antibodies were determined (by nephelometry and second-generation anti-CCP enzyme-linked immunosorbent assay, respectively). The subjects were followed up every 4 months via a structured interview (Community Oriented Program for Control of Rheumatic Diseases [COPCORD] questionnaire). When the COPCORD questionnaire indicated possible arthritis, subjects underwent an in-office rheumatology assessment including joint count. The study end point was defined as fulfillment of the American College of Rheumatology criteria for RA. RESULTS: Eight hundred nineteen initially healthy relatives of 252 patients with RA were included (69% female, 41% offspring, mean ± SD age 35 ± 12 years). Eleven (1.3%) were positive for both anti-CCP-2 and RF, 12 (1.5%) only for anti-CCP-2, and 16 (2%) only for RF. RA developed in 17 (2.1%) of the relatives during the 5-year followup (3,313 person-years for the seronegative group and 60.8 person-years for the anti-CCP-2-positive group). The PPV was 64% when both anti-CCP-2 and RF were positive and 58% when only anti-CCP-2 was positive. Offspring of patients with RA had an independent 3-fold increased risk of developing RA. CONCLUSION: Results of the present study indicate that the magnitude of risk for developing RA in healthy relatives of patients with RA can be estimated using simple routine laboratory tests.

Divergent perceptions in health-related quality of life between family members and patients with rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis.

The aim of this study was to assess whether family members perceive health-related quality of life (HRQoL) of family members with rheumatic illnesses differently from the perceptions of these patients themselves. Cross-sectional study of consecutive patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and ankylosing spondylitis (AS) attending two outpatient rheumatic clinics. HRQoL was assessed using the Spanish version of the World Health Organization Disability Assessment Scale (WHODAS-II) questionnaire; the "proxy" version is available for relatives. All patients and one proxy per patient separately answered the questionnaire at the clinic. Differences were determined by coefficients of determination (r (2)), Z scores, and meaningful differences of 30 %. Two hundred and ninety-one patients (111 SLE, 100 RA, and 80 AS) and their respective proxies were included. The mean age was 35 ± 13 years in SLE, 49.5 ± 14 years in RA, and 40 ± 14 years in AS patients. Divergent perceptions between patients and their proxies were found in 57 % of the SLE group, in 69 % of the RA group, and in 47 % of the AS group as per WHODAS-II global score. Stronger disagreement occurred for all the three groups in domains representing cognition and interaction with other people: around 60 % in the SLE group, 80 % in the RA group, and 40 % in the AS group. A substantial proportion of family members perceived the HRQoL of rheumatic family members differently from the perception of the patients themselves, most of the time biased toward underestimation, suggesting problems in the dynamics of efficient communication and social support.

The number needed to offend: a cross-sectional study of potential offensiveness of rheumatic diagnostic labels.

This study aims to explore the different connotations and potential offensiveness of ten mechanistic labels in newly referred Mexican patients with rheumatic symptoms as well as in Mexican and Canadian rheumatologists. Patients with musculoskeletal complaints newly referred for a rheumatology assessment were interviewed consecutively before they saw the rheumatologist. Patients were asked to choose one of nine feelings provoked by ten different illness mechanism labels. Rheumatologists gave a medical diagnosis after seeing the patients. Mexican and Canadian rheumatologists were invited to answer a structured questionnaire about their feelings at the moment they identified each of the ten different provided scenarios. Patients' and rheumatologists' feelings were classified as "offended" or "nonoffended." The "offensive score" was used to calculate a "number needed to offend" (NNO). One hundred and fifty patients were included. Inherited, immunological, and inflammatory labels had the fewest negative connotations (NNOs 17, 12, and 14, respectively), and psychological, functional, idiopathic, and sleep disturbance labels had the most (NNO 2 and 3, respectively). Functional labels were almost four times more offensive than organic labels. Stratified by rheumatologist diagnosis, patients with functional disorders were more accepting of organic-based mechanistic labels. A higher potential to offend was observed when patients with functional somatic conditions were given functional mechanistic labels (NNOs 1 to 4). The survey was completed by 186 Mexican rheumatologists and 71 Canadian rheumatologists. Primarily functional disorders such as somatization and anxiety had a high potential to evoke offensive feelings (NNOs 3 to 7). No significant differences in the NNO were found between Mexican and Canadian rheumatologists. Getting or giving mechanistic/explanatory labels is emotional. Both patients and rheumatologists experienced offended feelings with functional or idiopathic labels.

Cost of medication errors in rheumatic patients in Mexico.

This study aims to measure the frequency of medication error (ME) in rheumatology outpatients of the Social Security System (SS) in Mexico and to measure the costs by comparing the days lost at work as direct consequence of the medication error against the theoretical cost of no error in the process. A prospective 6-month survey was conducted in a reference hospital in Guadalajara, Mexico. ME was defined as any discrepancy between the prescription and medicine taken by patients. The origin of the discrepancy was identified and registered. We present 381 patients: 292 with rheumatoid arthritis, 57 with ankylosing spondylitis, and 32 with systemic lupus erythematosus. One hundred twenty seven (33%) had medication errors. Ninety eight (77%) got worse in their condition due to ME. Forty percent of MEs were due to patients' decisions, 41% to a lack of availability of medication which should have been provided by SS, and 18% to a non-justified medical decision by primary-care providers. Patients lost in average 3 working days each month because of the ME. The cost of ME is high. In the case analyzed, opportune access to treatment represents a lower cost for the system, but it represents a significant loss of days at work each month. ME is a signal of a system failure. Inter-professional teamwork is needed to perfect the system.

Fifteen-year trends of long-term disability and sick leaves in ankylosing spondylitis.

The aim of this study is to assess the trends in work disability and sick leave in ankylosing spondylitis (AS). In 1993 and 2007, patients diagnosed with AS that attended to a secondary- or a tertiary-care outpatient rheumatology clinics were evaluated for demographics, disease characteristics, axial mobility, working status, and work days missed due to sick leave or permanent disability. Factors that impacted labor status were identified by multiple regression analysis. In 1993, 91 study individuals (mean age 35 years, mean disease duration 10 ± 8 years) included 28 (31%) on permanent disability and 63 currently working; of these 63, 42 (67%) had missed at least 1 work day in the previous 12 months (mean 69 ± 63 days). In the next 5 years, the annual permanent disability was 3%. In 2007, 185 study individuals (mean age 42, mean disease duration 12 ± 10 years) included 53 (39%) on permanent disability and 132 active workers; 35 (66%) out of the 53 began permanent disability between 1999 and 2007 (2.1% annual disability rate), and 53 (40%) out of 132 active workers missed at least 1 work day in the previous 12 months (mean 52 ± 63 days). Only age predicted disability, with 10% and 11% increases in risk per year in 1993 and 2007, respectively (hazard ratios 1.09 and 1.11, respectively; p = 0.03 for both). Although the impact of AS on work seems to decrease slightly during the last 15 years, the actual impact is still substantial. An important proportion of patients went on permanent disability in the three decades before retirement. Extrapolating these results to official data for the year 2005, we may infer that between 1.3 million and nearly 15 million working days were missed that year due to AS.

Tendinous and ligamentous derangements in systemic lupus erythematosus.

OBJECTIVE: We assessed the prevalence of selected clinical and radiological features of tendinous and ligamentous derangements in a consecutive sample of patients with systemic lupus erythematosus (SLE). METHODS: Consecutive patients with SLE with no comorbidities attending a tertiary care center were prospectively assessed and underwent plain radiographic evaluation of the pelvis. Radiographs were analyzed by 2 blinded observers; radiographic sacroiliitis was graded 0 to IV. To better assess sacroiliac (SI) involvement, a computed tomography (CT) scan of the SI joints was performed in patients with grade III sacroiliitis. Hip joints and pubis were also assessed as described. RESULTS: Of the 192 included patients, 89% were female, mean age was 36 years, and mean disease duration was 10 years. Inflammatory low back pain was reported by 10% of patients. Sacroiliitis of any grade was observed in 31 patients (16%), and grade III (confirmed on CT scan) sacroiliitis was observed in 6% (95% CI 3% to 9%). Osteitis pubis was diagnosed in 6% (95% CI 3% to 10%) and coxofemoral migration in 8% (95% CI 2% to 9%). Jaccoud's arthropathy was found in 23%. Demographic and clinical variables were not statistically associated with radiographic sacroiliitis. CONCLUSION: Sacroiliitis and other tendinous and ligamentous derangements are not uncommon in patients with SLE. Based on these features and on previous reports, the term "SLE-related tendinous and ligamentous derangements" may be used to establish a common framework for further research and reporting.

Drug allergies may be more frequent in systemic lupus erythematosus than in rheumatoid arthritis.

OBJECTIVE: To measure the frequency of drug allergies in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), and register the causal drug, the type, and severity of the reaction. MATERIAL AND METHODS: Direct interview and chart review in patients with RA and SLE were conducted. We registered demographic data, drug allergies, the causal drug, how causality was assessed, and the type and severity of the allergic reaction. We include as drug allergies only those cases in which the result of exposure and re-exposure was known or in which a physician evaluating the original event established the causality link with the suspected drug. Differences between groups were assessed by chi test. RESULTS: Two hundred ninety-three RA and 58 patients with SLE were included. Fifty-three of the patients with RA (18%) and 20 of the patients with SLE (34.3%, P = 0.049) reported drug allergies. Most of them presented skin rash as their clinical expression of allergy (73%); anaphylaxis was reported in 4 cases (5%). Allergy to sulfa drugs is found more frequently in SLE (P = 0.0079). No differences were found when comparing the frequency of other drug allergies, such as penicillin and metamizole. DISCUSSION: Drug allergies are more frequent in SLE than in RA. Sulfa drugs are still the most frequent cause of drug allergies in SLE. Allergies because of drugs forbidden in the United States but easily available in specific ethnic groups are frequent in patients with SLE and RA. Their specific consumption must be intentionally assessed in cases of suspected drug allergies.

Agudeza diagnóstica del examen físico de rodilla en la artritis reumatoide: estudio clínico y sonográfico del derrame articular y quiste de Baker / Diagnostic accuracy of physical examination of the knee in rheumatoid arthritis: clinical and ultrasonographic study of joint effusion and Baker’s cyst

Introducción: En pacientes con artritis reumatoide (AR),el dolor en las rodillas puede ser inflamatorio, mecánico oextraarticular. La exploración física (EF) no siempredetecta el derrame articular o el quiste de Baker (QB) enlas rodillas de estos pacientes.Objetivo: Determinar la agudeza diagnóstica de la EF enel diagnóstico de derrame articular y QB en pacientes conAR evaluados con ultrasonografía osteomuscular(USME), la técnica de imagen de referencia.Material y método: Se utilizaron 3 equipos de ultrasonidomarca Toshiba Tosbee, Toshiba Capasee y SiemensSonoline, con transductores lineares de 7,5 MHz paradetectar derrame y QB en rodillas de pacientes con ARvalorados previamente por clínica por un reumatólogo,quien dictaminó si los había. Se registraron edad, sexo,duración de la AR, factor reumatoide, tratamiento, clasefuncional de AR (CFAR) y diagnóstico clínico previo alUSME.Resultados: Se evaluó a 40 pacientes (80 rodillas) conAR, el 80% eran mujeres, la edad promedio fue 61,3 ±15 años y la duración de la enfermedad, 9,5 ± 11,3 años;el factor reumatoide fue positivo en el 80% de los casos;CFAR I (3 pacientes), CFAR II (27), CFAR III (8),CFAR IV (2); el 55% de los pacientes recibíanmetotrexato. Hubo dolor referido por el paciente en 26rodillas (32,5%). Se comunicó derrame por USME en49 rodillas (61,2%) y QB en 14 (17,5%); derrame porEF en 35 rodillas (43,7%) y corroborado por USME en31 rodillas (38,75%), QB por clínica en 12 rodillas(15%) y corroborado por USME en 6 rodillas (7,5%).La sensibilidad de la EF para la detección de derrame fue 0,63 y la especificidad, 0,87; para la detección de QBfueron 0,43 y 0,91, respectivamente.Conclusiones: La EF mostró una agudeza diagnósticaaceptable para el clínico. El uso complementario de laUSME en la EF de los pacientes con AR puede ser unfactor decisivo en la conducta terapéutica y diagnóstica enpacientes con AR y afección de rodillas(AU)

Introduction: In patients with rheumatoid arthritis (RA),knee pain can be inflammatory, mechanical or extraarticular.The physical examination (PE) doesn’t alwaysdetect the presence of knee joint effusion or Baker’s cyst(BC) in the knees of these patients.Objective: To determine the diagnostic accuracy of PE inthe diagnosis of effusion and BC in patients with RAevaluated with musculoskeletal ultrasound (MSUS),using this technique as the gold standard for comparison.Material and method: Three different models ofultrasound machines with a 7.5 MHz linear probe wereused (Toshiba Tosbee, Toshiba Capasee and SiemensSonoline). A rheumatologist evaluated the presence orabsence of knee joint effusion or BC in patients. Weregistered age, gender, time of evolution of RA,rheumatoid factor, treatment, functional class of RA(FCRA) and previous clinical diagnosis to the MSUSstudy.Results: 40 patients (80 knees) with RA were evaluated.Eighty percent were women, mean age 61.3 ± 15 years.Time since onset of RA was 9.5 ± 11.3 years, rheumatoidfactor was positive in 80%, FCRA I (3 patients), FCRA II (27), FCRA III (8), FCRA IV (2). Fifty five percent ofthe patients received methotrexate. Patients reffered painin 26 knees (32.5%). Joint effusion was reported by theclinician in 35 knees (43.7%) and corroborated by MSUSin 31 knees (38.75%), BC was reported by the clinician in12 knees (15%) and corroborated by MSUS in 6 knees(7.5%). The sensitivity of the PE for detection of jointeffusion was 0.63 and specificity of 0.87, for the detectionof BC was 0.43 and 0.91, respectively.Conclusions: The PE showed acceptable diagnosticaccuracy for the clinician. The complementary use of theMSUS can change the therapeutic and diagnosticapproach in patients with RA(AU)

Cyclophosphamide boluses induce micronuclei expression in buccal mucosa cells of patients with systemic lupus erythematosus independent of cytochrome P450 2D6 status.

OBJECTIVE: To assess the effect of cyclophosphamide (CYC) and the influence of CYP2D6 polymorphism on micronuclei expression in patients with systemic lupus erythematosus (SLE). METHODS: Micronuclei (MN) assays were performed in oral mucosa sweeps of 49 patients with SLE, receiving and not receiving CYC therapy, and 43 healthy controls. In patients receiving CYC the MN assay was repeated 14 days after CYC administration. SLE patients underwent determination of the CYP2D6 allele expressed in peripheral blood by polymerase chain reaction amplification. These results were compared with CYP2D6 distribution in a healthy population from the same geographic area. The results were analyzed by Mann-Whitney U and chi-square tests. RESULTS: Twenty-four patients with SLE received CYC boluses. The mean age of SLE patients was 32 +/- 10 years; mean disease duration was 7 +/- 6 years. Basal expression of MN was similar in the groups investigated and increased significantly in those exposed to CYC (CYC group 44%, no CYC group 5%, healthy controls 9%; p = 0.001). We found no association between the CYP2D6 allele expressed and MN induction. Poor metabolizers were overrepresented in SLE subjects as compared with 139 healthy controls (p < 0.05). CONCLUSION: Genotoxicity, as assessed by the MN assay, is increased in patients with SLE after CYC boluses. The CYP2D6 allele expressed in SLE patients does not have a role in CYC induced chromosomal injury.

New insights into culture driven disorders.

Rheumatologists frequently encounter patients whose illnesses lack face-value; that is, they lack the typical objective features of pathology that rheumatologists traditionally rely on for diagnosis and developing effective treatment approaches: namely fibromyalgia, chronic fatigue syndrome, Gulf War syndrome, chronic whiplash, chronic low back pain, etc. In this article, we examine this group of illnesses as culture-driven disorders to emphasize the central importance of various societal constraints in the ultimate presentation of patients with these illnesses. We will examine them by first understanding the purpose they serve, the underlying factors that compel societal institutions to sanctify these disorders as diseases, and how research is beginning to examine the behaviour that captures and packages these symptoms to produce their clinical presentation. With this research understanding, rheumatologists may be able to offer patients more useful action plans, but likely changes in societal approaches to the expressions of distress and changes in disability and compensation systems will also be required.

Validation of the Spanish version of a screening questionnaire for the detection of systemic lupus erythematosus.

The aim of this study was to assess the sensitivity, specificity, positive and negative predictive values of the translation of a screening questionnaire for systemic lupus erythematosus (SLE) in Spanish-speaking populations. The questionnaire was applied to secondary-care outpatients in a rheumatology clinic. Sensitivity, specificity, predictive positive and negative values of the instrument, and the best cut-off point to discriminate between SLE patients and other conditions, were determined. Fifty-two subjects answered the questionnaire (21 patients with SLE, 15 with a possible diagnosis of SLE who eventually proved not to have the disease, and 16 healthy volunteers), which can be answered in 2 min. The best cut-off point was three affirmative answers (95% specificity, 84% sensitivity, 80% predictive positive and 96% predictive negative values). The questionnaire can discriminate between SLE cases and other conditions. Sensitivity and specificity are close to those of the original English version. Applying this instrument can help to acquire informed estimates of SLE prevalence.

Las enfermedades reumáticas en el México colonial / Rheumatic diseases in colonial Mexico

Las obras médicas publicadas en la Nueva España entre los siglos XVI y XVIII no han sido tomadas en cuenta hasta ahora en la búsqueda de descripciones de la artritis reumatoide y de otras enfermedades reumáticas previas a las descripciones hechas por Sydenham. Revisamos la mayoría de las obras médicas publicadas en la Nueva España desde la llegada de los españoles hasta el siglo XVIII y dividimos a las enfermedades descritas con manifestaciones articulares en cuatro grupos de acuerdo con sus manifestaciones clínicas principales: dolor sin inflamación en una región anatómica, dolor sin inflamación en varias articulaciones e inflamación en las articulaciones, y manifestaciones articulares relacionadas con procesos contagiosos. Encontramos que cien años antes que Sydenham, se diferenciaba entre la gota y la artritis reumatoide por su forma de evolución, y presentamos la más antigua descripción conocida de las artritis reactivas