Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC.

BACKGROUND: Amivantamab plus lazertinib (amivantamab-lazertinib) has shown clinically meaningful and durable antitumor activity in patients with previously untreated or osimertinib-pretreated EGFR (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC). METHODS: In a phase 3, international, randomized trial, we assigned, in a 2:2:1 ratio, patients with previously untreated EGFR-mutated (exon 19 deletion or L858R), locally advanced or metastatic NSCLC to receive amivantamab-lazertinib (in an open-label fashion), osimertinib (in a blinded fashion), or lazertinib (in a blinded fashion, to assess the contribution of treatment components). The primary end point was progression-free survival in the amivantamab-lazertinib group as compared with the osimertinib group, as assessed by blinded independent central review. RESULTS: Overall, 1074 patients underwent randomization (429 to amivantamab-lazertinib, 429 to osimertinib, and 216 to lazertinib). The median progression-free survival was significantly longer in the amivantamab-lazertinib group than in the osimertinib group (23.7 vs. 16.6 months; hazard ratio for disease progression or death, 0.70; 95% confidence interval [CI], 0.58 to 0.85; P<0.001). An objective response was observed in 86% of the patients (95% CI, 83 to 89) in the amivantamab-lazertinib group and in 85% of those (95% CI, 81 to 88) in the osimertinib group; among patients with a confirmed response (336 in the amivantamab-lazertinib group and 314 in the osimertinib group), the median response duration was 25.8 months (95% CI, 20.1 to could not be estimated) and 16.8 months (95% CI, 14.8 to 18.5), respectively. In a planned interim overall survival analysis of amivantamab-lazertinib as compared with osimertinib, the hazard ratio for death was 0.80 (95% CI, 0.61 to 1.05). Predominant adverse events were EGFR-related toxic effects. The incidence of discontinuation of all agents due to treatment-related adverse events was 10% with amivantamab-lazertinib and 3% with osimertinib. CONCLUSIONS: Amivantamab-lazertinib showed superior efficacy to osimertinib as first-line treatment in EGFR-mutated advanced NSCLC. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.).

Durvalumab versus placebo with chemoradiotherapy for locally advanced cervical cancer (CALLA): a randomised, double-blind, phase 3 trial.

BACKGROUND: Concurrent chemoradiotherapy has been the standard of care for locally advanced cervical cancer for over 20 years; however, 30-40% of treated patients have recurrence or progression within 5 years. Immune checkpoint inhibition has improved outcomes for patients with PD-L1 positive metastatic or recurrent cervical cancer. We assessed the benefit of adding durvalumab, a PD-L1 antibody, with and following chemoradiotherapy for locally advanced cervical cancer. METHODS: The CALLA randomised, double-blind, phase 3 trial included 105 hospitals across 15 countries. Patients aged at least 18 years with previously untreated locally advanced cervical cancer (adenocarcinoma, squamous, or adenosquamous; International Federation of Gynaecology and Obstetrics [FIGO] 2009 stage IB2-IIB lymph node positive, stage ≥III any lymph node status) and WHO or Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (1:1) through an interactive web response system using a permuted block size of 4 to receive durvalumab (1500 mg intravenously once every 4 weeks) or placebo with and following chemoradiotherapy, for up to 24 cycles. Chemoradiotherapy included 45 Gy external beam radiotherapy at 5 fractions per week concurrent with intravenous cisplatin (40 mg/m2) or carboplatin (area under the concentration-time curve 2) once weekly for 5 weeks, followed by image-guided brachytherapy (high-dose rate, 27·5-30 Gy or low-dose/pulse-dose rate, 35-40 Gy). Randomisation was stratified by disease stage status (FIGO stage and node status) and geographical region. Chemoradiotherapy quality was continuously reviewed. The primary endpoint was progression-free survival, assessed by the investigator using Response Evaluation Criteria in Solid Tumors, version 1.1, in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03830866. FINDINGS: Between Feb 15, 2019, and Dec 10, 2020, 770 women were randomly assigned (385 to durvalumab and 385 to placebo; median age 49 years [IQR 41-57]). Median follow-up was 18·5 months (IQR 13·2-21·5) in the durvalumab group and 18·4 months (13·2-23·7) in the placebo group. At data cutoff, median progression-free survival had not been reached (95% CI not reached-not reached) for either group (HR 0·84; 95% CI 0·65-1·08; p=0·17); 12-month progression-free survival was 76·0% (71·3-80·0) with durvalumab and 73·3% (68·4-77·5) with placebo. The most frequently reported grade 3-4 adverse events in both groups were anaemia (76 [20%] of 385 in the durvalumab group vs 56 [15%] of 384 in the placebo group) and decreased white blood cells (39 [10%] vs 49 [13%]). Serious adverse events occurred for 106 (28%) patients who received durvalumab and 89 (23%) patients who received placebo. There were five treatment-related deaths in the durvalumab group (one case each of urinary tract infection, blood loss anaemia, and pulmonary embolism related to chemoradiotherapy only; one case of endocrine disorder related to durvalumab only; and one case of sepsis related to both durvalumab and chemoradiotherapy). There was one treatment-related death in the placebo group (pneumonia related to chemoradiotherapy). INTERPRETATION: Durvalumab concurrent with chemoradiotherapy was well tolerated in participants with locally advanced cervical cancer, however it did not significantly improve progression-free survival in a biomarker unselected, all-comers population. Concurrent durvalumab plus chemoradiotherapy warrants further exploration in patients with high tumoral PD-L1 expression. Rigorous monitoring ensured high chemoradiotherapy compliance with advanced technology and allowed patients to receive optimal care. FUNDING: AstraZeneca.

Nivolumab plus rucaparib for metastatic castration-resistant prostate cancer: results from the phase 2 CheckMate 9KD trial.

BACKGROUND: CheckMate 9KD (NCT03338790) is a non-randomized, multicohort, phase 2 trial of nivolumab plus other anticancer treatments for metastatic castration-resistant prostate cancer (mCRPC). We report results from cohorts A1 and A2 of CheckMate 9KD, specifically evaluating nivolumab plus rucaparib. METHODS: CheckMate 9KD enrolled adult patients with histologically confirmed mCRPC, ongoing androgen deprivation therapy, and an Eastern Cooperative Oncology Group performance status of 0-1. Cohort A1 included patients with postchemotherapy mCRPC (1-2 prior taxane-based regimens) and ≤2 prior novel hormonal therapies (eg, abiraterone, enzalutamide, apalutamide); cohort A2 included patients with chemotherapy-naïve mCRPC and prior novel hormonal therapy. Patients received nivolumab 480 mg every 4 weeks plus rucaparib 600 mg two times per day (nivolumab dosing ≤2 years). Coprimary endpoints were objective response rate (ORR) per Prostate Cancer Clinical Trials Working Group 3 and prostate-specific antigen response rate (PSA50-RR; ≥50% PSA reduction) in all-treated patients and patients with homologous recombination deficiency (HRD)-positive tumors, determined before enrollment. Secondary endpoints included radiographic progression-free survival (rPFS), overall survival (OS), and safety. RESULTS: Outcomes (95% CI) among all-treated, HRD-positive, and BRCA1/2-positive populations for cohort A1 were confirmed ORR: 10.3% (3.9-21.2) (n=58), 17.2% (5.8-35.8) (n=29), and 33.3% (7.5-70.1) (n=9); confirmed PSA50-RR: 11.9% (5.9-20.8) (n=84), 18.2% (8.2-32.7) (n=44), and 41.7% (15.2-72.3) (n=12); median rPFS: 4.9 (3.7-5.7) (n=88), 5.8 (3.7-8.4) (n=45), and 5.6 (2.8-15.7) (n=12) months; and median OS: 13.9 (10.4-15.8) (n=88), 15.4 (11.4-18.2) (n=45), and 15.2 (3.0-not estimable) (n=12) months. For cohort A2 they were confirmed ORR: 15.4% (5.9-30.5) (n=39), 25.0% (8.7-49.1) (n=20), and 33.3% (7.5-70.1) (n=9); confirmed PSA50-RR: 27.3% (17.0-39.6) (n=66), 41.9 (24.5-60.9) (n=31), and 84.6% (54.6-98.1) (n=13); median rPFS: 8.1 (5.6-10.9) (n=71), 10.9 (6.7-12.0) (n=34), and 10.9 (5.6-12.0) (n=15) months; and median OS: 20.2 (14.1-22.8) (n=71), 22.7 (14.1-not estimable) (n=34), and 20.2 (11.1-not estimable) (n=15) months. In cohorts A1 and A2, respectively, the most common any-grade and grade 3-4 treatment-related adverse events (TRAEs) were nausea (40.9% and 40.8%) and anemia (20.5% and 14.1%). Discontinuation rates due to TRAEs were 27.3% and 23.9%, respectively. CONCLUSIONS: Nivolumab plus rucaparib is active in patients with HRD-positive postchemotherapy or chemotherapy-naïve mCRPC, particularly those harboring BRCA1/2 mutations. Safety was as expected, with no new signals identified. Whether the addition of nivolumab incrementally improves outcomes versus rucaparib alone cannot be determined from this trial. TRIAL REGISTRATION NUMBER: NCT03338790.

Clinical features associated with neurosyphilis in people living with HIV and late latent syphilis.

BACKGROUND: The diagnosis of neurosyphilis is a challenge, and the criteria for deciding when to perform a lumbar puncture are still controversial, especially in people living with HIV with a late latent syphilis diagnosis. METHODS: Retrospective analysis of demographic, clinical, and laboratory data of people with HIV and documented late latent syphilis or syphilis of unknown duration with a cerebrospinal fluid VDRL test. RESULTS: 122 patients were evaluated, of whom 52 had the diagnosis of neurosyphilis. Patients with and without neurosyphilis presented a similar viral load and lymphocyte CD4+ T-cell count. Neurological symptoms (OR 6.4, 95% CI 2.1-22.4; p < 0.01), serum VDRL titers of 1:32 (p<0.01), 1:64 (p = 0.055), and ≥1:128 (p < 0.001) were associated with neurosyphilis. Furthermore, serum VDRL ≥1:32 were associated with (OR 24.9, 95% CI 5.45-154.9; p < 0.001) or without (OR 6.5, 95% CI 2.0-29.2; p = 0.004) neurological symptoms with neurosyphilis; however, VDRL ≤1:16 with neurological symptoms can be associated with neurosyphilis (OR 7.6, 95% CI 1.03-64.3; p = 0.046). CONCLUSION: Neurological symptoms, particularly headache, were predictors of neurosyphilis in people with HIV irrespective of their viral load and lymphocyte CD4+ T-cell count in late latent syphilis. A serum VDRL ≥1:32 increased the risk of neurosyphilis in patients with or without any symptoms.

Nivolumab plus docetaxel in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer: results from the phase II CheckMate 9KD trial.

BACKGROUND: Docetaxel has immunostimulatory effects that may promote an immunoresponsive prostate tumour microenvironment, providing a rationale for combination with nivolumab (programmed death-1 inhibitor) for metastatic castration-resistant prostate cancer (mCRPC). METHODS: In the non-randomised, multicohort, global phase II CheckMate 9KD trial, 84 patients with chemotherapy-naive mCRPC, ongoing androgen deprivation therapy and ≤2 prior novel hormonal therapies (NHTs) received nivolumab 360 mg and docetaxel 75 mg/m2 every 3 weeks with prednisone 5 mg twice daily (≤10 cycles) and then nivolumab 480 mg every 4 weeks (≤2 years). The co-primary end-points were objective response rate (ORR) and prostate-specific antigen response rate (PSA50-RR; ≥50% decrease from baseline). RESULTS: The confirmed ORR (95% confidence interval [CI]) was 40.0% (25.7-55.7), and the confirmed PSA50-RR (95% CI) was 46.9% (35.7-58.3). The median (95% CI) radiographic progression-free survival (rPFS) and overall survival (OS) were 9.0 (8.0-11.6) and 18.2 (14.6-20.7) months, respectively. In subpopulations with versus without prior NHT, the ORR was 38.7% versus 42.9%, the PSA50-RR was 39.6% versus 60.7%, the median rPFS was 8.5 versus 12.0 months and the median OS was 16.2 months versus not reached. Homologous recombination deficiency status or tumour mutational burden did not appear to impact efficacy. The most common any-grade and grade 3-4 treatment-related adverse events were fatigue (39.3%) and neutropenia (16.7%), respectively. Three treatment-related deaths occurred (1 pneumonitis related to nivolumab; 2 pneumonias related to docetaxel). CONCLUSIONS: Nivolumab plus docetaxel has clinical activity in patients with chemotherapy-naïve mCRPC. Safety was consistent with the individual components. These results support further investigation in the ongoing phase III CheckMate 7DX trial. CLINICALTRIALS. GOV REGISTRATION: NCT03338790.

Rheumatological therapy in Prehispanic Mesoamerica.

Nahuatl medicine was remarkably advanced in Prehispanic Mesoamerica. Thoughts on health and disease were different to those prevalent in Europe in the sixteenth century because they included magic, religion and different kinds of animal, mineral and, notably, herbal medicine. These resources were used in a supplementary, not isolated, way by Nahua physicians (ticitl) according to patients' needs and beliefs. Most Nahua physicians had similar knowledge but there were some differences between rural and urban areas, and those who were also doctor-priests of a particular deity. After the European colonization of Mesoamerica, great efforts were made by Spaniards and Indians to recover the immense amount of ancient knowledge in Mesoamerica related to medicine. Some of this work, not all, is included in the Cruz-Badiano Codex, the Florentine Codex or Historia general de las cosas de la Nueva España, and the Francisco Hernández Codex. A review of these codices and the recent literature on the practice of Nahua Medicine was performed with particular interest in herbal medicine in rheumatic diseases, or symptoms probably related to rheumatic diseases, during the sixteenth century in the land currently known as Mexico.

Terapéutica reumatológica en la mesoamérica prehispánica / Rheumatological Therapy in Prehispanic Mesoamerica

La medicina náhuatl tenía un notable desarrollo en la Mesoamérica prehispánica. El concepto de salud y enfermedad era diferente al que en el siglo XVI prevalecía en Europa e incluía conceptos de magia, religión, empleo de recursos físicos, de animales, de minerales y, muy destacadamente, de la herbolaria. El médico nahua (ticitl) no utilizaba estos recursos en forma aislada sino de manera complementaria de acuerdo con las características de cada paciente. Los médicos compartían conocimientos generales comunes, pero había diferencias entre los que vivían en las zonas rurales, los de la ciudad y los médicos-sacerdotes. En los años que siguieron a las guerras de conquista se hicieron esfuerzos para recopilar las características de la medicina en Mesoamérica. Algunos de estos trabajos, no los únicos, son el Códice De la Cruz-Badiano, el Códice Florentino o Historia general de las cosas de la Nueva España y el Códice Francisco Hernández. Se llevó a cabo una revisión de estos códices y de la literatura reciente referente a la práctica médica náhuatl con énfasis en la herbolaria como recurso terapéutico para los padecimientos reumatológicos en el siglo XVI, en los territorios que ahora conocemos como México.(AU)

Nahuatl medicine was remarkably advanced in Prehispanic Mesoamerica. Thoughts on health and disease were different to those prevalent in Europe in the sixteenth century because they included magic, religion and different kinds of animal, mineral and, notably, herbal medicine. These resources were used in a supplementary, not isolated, way by Nahua physicians (ticitl) according to patients’ needs and beliefs. Most Nahua physicians had similar knowledge but there were some differences between rural and urban areas, and those who were also doctor-priests of a particular deity. After the European colonization of Mesoamerica, great efforts were made by Spaniards and Indians to recover the immense amount of ancient knowledge in Mesoamerica related to medicine. Some of this work, not all, is included in the Cruz-Badiano Codex, the Florentine Codex or Historia general de las cosas de la Nueva España, and the Francisco Hernández Codex. A review of these codices and the recent literature on the practice of Nahua Medicine was performed with particular interest in herbal medicine in rheumatic diseases, or symptoms probably related to rheumatic diseases, during the sixteenth century in the land currently known as Mexico.(AU)

Prevalence and risk factors of chronic kidney disease in an HIV positive Mexican cohort.

BACKGROUND: HIV subjects have several kidney pathologies, like HIV-associated nephropathy or antiretroviral therapy injury, among others. The global prevalence of Chronic Kidney Disease (CKD) is 8-16%; however, in HIV subjects, the prevalence varies between geographic regions (2-38%). The aim was to determine the prevalence of CKD and identify the associated risk factors. METHODS: A longitudinal descriptive study was carried out at the 'Hospital Civil de Guadalajara' Feb'18 - Jan'19. Basal clinical, demographic, opportunistic infections (OI), and laboratory data were obtained at months 0 and 3; inclusion criteria were ≥ 18 years old, naïve HIV + , urine albumin/creatinine ratio, serum creatinine & urine test, and signed informed consent. Descriptive and multiple logistic regression statistical analyses were made. RESULTS: One hundred twenty subjects were included; 92.5% were male, 33 ± 9.5 years, 60% consumed tobacco, 73% alcohol, and 59% some type of drug. The CKD prevalence was 15.8%. CKD patients had a higher risk of hepatitis C virus coinfection, Relative Risk (RR):5.9; HCV infection, RR:4.3; ≥ 30 years old, RR:3.9; C clinical-stage, RR:3.5; CD4+ T cells count < 200 cells/µL, RR: 2.4; and HIV-1 viral load ≥ 100,000 cop/mL, RR: 2.7. CONCLUSIONS: Our study showed a higher CKD prevalence in patients with HIV; higher CKD development with coinfections as Hepatitis C Virus and Mycobacterium tuberculosis. The identification and prompt management of CKD and coinfections should be considered to avoid the progression and to delay renal replacement therapy as long as possible.

Rheumatological Therapy in Prehispanic Mesoamerica. / Terapéutica reumatológica en la mesoamérica prehispánica.

Nahuatl medicine was remarkably advanced in Prehispanic Mesoamerica. Thoughts on health and disease were different to those prevalent in Europe in the sixteenth century because they included magic, religion and different kinds of animal, mineral and, notably, herbal medicine. These resources were used in a supplementary, not isolated, way by Nahua physicians (ticitl) according to patients' needs and beliefs. Most Nahua physicians had similar knowledge but there were some differences between rural and urban areas, and those who were also doctor-priests of a particular deity. After the European colonization of Mesoamerica, great efforts were made by Spaniards and Indians to recover the immense amount of ancient knowledge in Mesoamerica related to medicine. Some of this work, not all, is included in the Cruz-Badiano Codex, the Florentine Codex or Historia general de las cosas de la Nueva España, and the Francisco Hernández Codex. A review of these codices and the recent literature on the practice of Nahua Medicine was performed with particular interest in herbal medicine in rheumatic diseases, or symptoms probably related to rheumatic diseases, during the sixteenth century in the land currently known as Mexico.

Switching to Biosimilar SDZ-ADL in Patients with Moderate-to-Severe Active Rheumatoid Arthritis: 48-Week Efficacy, Safety and Immunogenicity Results From the Phase III, Randomized, Double-Blind ADMYRA Study.

BACKGROUND: Sandoz adalimumab SDZ-ADL (GP-2017) is an approved adalimumab biosimilar with similar efficacy and comparable safety and immunogenicity to reference adalimumab (ref-ADL) as confirmed by analytical, pharmacokinetic and confirmatory studies. ADMYRA, a phase III double-blind study, was conducted with an aim to generate efficacy, safety and immunogenicity comparability data in patients with moderate-to-severe rheumatoid arthritis (RA) having inadequate response to disease-modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX). The study also evaluated an aspect of 'switching' reference product to the biosimilar in terms of efficacy, safety and immunogenicity up to Week 48. METHODS: Eligible patients (N = 353) were randomized 1:1 to receive subcutaneous (sc) SDZ-ADL 40 mg (n = 177) or ref-ADL (n = 176) every other week from Week 0 to Week 24. At Week 24, all patients with at least a moderate response by Disease Activity Score-28 including high-sensitivity C-reactive protein (DAS28-CRP) in the SDZ-ADL group continued SDZ-ADL (n = 159), and in the ref-ADL group were switched to SDZ-ADL (n = 166), treated for up to 46 weeks. The primary endpoint was change in DAS28-CRP from baseline at Week 12. Other efficacy endpoints included proportion of patients with European League Against Rheumatism (EULAR) response, EULAR remission, Boolean remission, safety and immunogenicity. RESULTS: The DAS28-CRP score changes from baseline at Week 12 were similar between SDZ-ADL (- 2.16) and ref-ADL (- 2.18) with a mean difference (95% CI) of 0.02 (- 0.24 to 0.27), which was within the pre-specified equivalence margin of ± 0.6. After switching treatment from ref-ADL to SDZ-ADL, the mean DAS28-CRP change was similar between the SDZ-ADL and 'ref-ADL/switched SDZ-ADL' group (- 3.09 vs - 3.05). The proportion of patients with good/moderate EULAR response was 69.2%/29.0% in the SDZ-ADL group and 68.0%/29.6% in the 'ref-ADL/switched SDZ-ADL' group. The proportion of patients in EULAR remission was 51.4% and 54.4% and in Boolean remission was 16.8% and 21.6% for SDZ-ADL and 'ref-ADL/switched SDZ-ADL' groups, respectively. The secondary endpoints were similar across the treatment groups. The incidence of adverse events (AEs) and injection-site reactions were low and similar between SDZ-ADL and 'ref-ADL/switched SDZ-ADL' groups (AEs 70.6% vs 68.8%, injection-site reactions 4.0% vs 6.3%), and most of these patients experienced AEs of mild or moderate severity. Antidrug antibodies were detected in 24.2% and 25.6% of patients treated with SDZ-ADL and 'ref-ADL/switched SDZ-ADL', respectively, from baseline to Week 48, of which 72.5% in SDZ-ADL and 79.1% in 'ref-ADL/switched SDZ-ADL' groups were neutralizing. CONCLUSIONS: In patients with moderate-to-severe RA who had an inadequate response to DMARDs, SDZ-ADL demonstrated a similar efficacy and a comparable safety and immunogenicity profile to ref-ADL. Efficacy was sustained after switching from ref-ADL to SDZ-ADL with no impact on safety (NCT02744755).

Bioactive Components in Human Milk Along the First Month of Life: Effects of Iodine Supplementation during Pregnancy.

BACKGROUND/AIMS: Human milk is considered the most suitable food for infants. The potential benefits of breastfeeding can be explained by the presence of different growth and neurotrophic factors in human milk. This study was designed to detect some biomarkers in human milk, which could be involved in the infant neurodevelopment and in the regulation of the maturation of neonatal intestine (brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), glial fibrillary acidic protein (GFAP), fibroblast growth factor 21 (FGF21), lysophosphatidic acid (LPA) and autotaxin (ATX)), and compare them on the basis of the consumption of iodine supplements or multivitamins. METHODS: A prospective study included 37 healthy breastfeeding mothers, divided into 3 different groups: (1) 10 mothers who did not take supplements, (2) 17 mothers who took potassium iodine (KI) 200 µg/day and (3) 10 mothers who took a multivitamin supplement. RESULTS: The concentrations of BDNF, GDNF, GFAP, FGF21, LPA and ATX in human milk were not significantly different in women who took a multivitamin or KI supplement compared with those who did not take any supplement. CONCLUSIONS: The presence of neurotrophic factors in human milk is neither modified by the consumption of supplements nor by their type.

Desempeño del examen clínico objetivo estructurado como instrumento de evaluación en la certificación nacional como reumatólogo / Performance of an objective structured clinical examination in a national certification process of trainees in rheumatology

Objetivo. Determinar la validez de constructo y la confiabilidad de un examen clínico objetivo estructurado (ECOE) en la evaluación de una certificación nacional como reumatólogo. Método. En 2013 y 2014, se aplicaron sendos ECOE y evaluación teórica (ET) a 32 y 38 residentes aspirantes a la certificación de reumatólogo, respectivamente. Se incluyeron 12 y 15 estaciones calificadas mediante lista de cotejo validada. Previamente, 3 reumatólogos certificados realizaron sendas pruebas piloto. Se calculó la puntuación global del ECOE y se evaluó su desempeño. Resultados. En 2013, la media ± DE del ECOE fue de 7,1 ± 0,6) y ningún aspirante tuvo calificación reprobatoria (CR); la media de la ET fue de 6,5 ± 0,6 y 7 aspirantes (21,9%) tuvieron CR (< 6). En 2014, la media del ECOE fue de 6,7 ± 0,6) y 3 aspirantes (7,9%) tuvieron CR, de los cuales 2 reprobaron la ET; la media de la ET fue de 6,4 ± 0,5) y 7 aspirantes (18,5%) tuvieron CR, 2 de los cuales reprobaron el ECOE. En 2013, la correlación entre el ECOE y la ET fue de r = 0,44, p = 0,006. En ambos años, los reumatólogos certificados obtuvieron mejores calificaciones en el ECOE que los residentes. El porcentaje de aprobados en la ET fue mayor entre quienes aprobaron el ECOE que entre quienes lo reprobaron: 86% vs. 67%, p = 0,02. Se aplicaron 9 estaciones en ambos años y sus puntuaciones mostraron correlación de 0,81 a 0,95, p ≤ 0,01. Conclusión. El ECOE es una herramienta adecuada para evaluar las competencias clínicas de los aspirantes a la certificación (AU)

Objective. To assess reliability and validity of the objectively-structured clinical examination (OSCE) applied in postgraduate certification processes by the Mexican Board of Rheumatology. Method. Thirty-two (2013) and 38 (2014) Rheumatology trainees (RTs) underwent an OSCE consisting of 12 and 15 stations respectively, scored according to a validated check-list, as well as 300-multiple-choice 300 question examination (MCQ). Previously, 3 certified rheumatologists underwent a pilot-OSCE. A composite OSCE score was obtained for each participant and its performance examined. Results. In 2013, OSCE mean score was 7.1 ± 0.6 with none RT receiving a failing score while the MCQ score was 6.5 ± 0.6 and 7 (21.9%) RTs receiving a failing (< 6) score. In 2014, the OSCE score was 6.7 ± 0.6, with 3 (7.9%) RTs receiving a failing score (2 of them also failed MCQ) while the MCQ score was 6.4 ± 0.5 and 7 (18.5%) RTs were disqualified (2 of them also failed OSCE). A significant correlation between the MCQ and the OSCE scores was observed in the 2013 (r=0.44; P=0.006). Certified rheumatologists performed better than RTs at both OSCE. Overall, 86% of RTs obtaining an OSCE passing score also obtained a MCQ passing score, while this was only 67% (P=.02) among those who obtained an OSCE failing score. Nine stations were applied at both consecutive years. Their performance was similar in both certification processes, with correlation coefficients ranging from 0.81 to 0.95 (P≤0.01). Conclusion. The OSCE is a valid and reliable tool to assess the Rheumatology clinical skills in RTs (AU)

Performance of an objective structured clinical examination in a national certification process of trainees in rheumatology.

OBJECTIVE: To assess reliability and validity of the objectively-structured clinical examination (OSCE) applied in postgraduate certification processes by the Mexican Board of Rheumatology. METHOD: Thirty-two (2013) and 38 (2014) Rheumatology trainees (RTs) underwent an OSCE consisting of 12 and 15 stations respectively, scored according to a validated check-list, as well as 300-multiple-choice 300 question examination (MCQ). Previously, 3 certified rheumatologists underwent a pilot-OSCE. A composite OSCE score was obtained for each participant and its performance examined. RESULTS: In 2013, OSCE mean score was 7.1±0.6 with none RT receiving a failing score while the MCQ score was 6.5±0.6 and 7 (21.9%) RTs receiving a failing (< 6) score. In 2014, the OSCE score was 6.7±0.6, with 3 (7.9%) RTs receiving a failing score (2 of them also failed MCQ) while the MCQ score was 6.4±0.5 and 7 (18.5%) RTs were disqualified (2 of them also failed OSCE). A significant correlation between the MCQ and the OSCE scores was observed in the 2013 (r=0.44; P=0.006). Certified rheumatologists performed better than RTs at both OSCE. Overall, 86% of RTs obtaining an OSCE passing score also obtained a MCQ passing score, while this was only 67% (P=.02) among those who obtained an OSCE failing score. Nine stations were applied at both consecutive years. Their performance was similar in both certification processes, with correlation coefficients ranging from 0.81 to 0.95 (P≤0.01). CONCLUSION: The OSCE is a valid and reliable tool to assess the Rheumatology clinical skills in RTs.

Es necesario desarrollar el profesionalismo médico / It is necessary to develop medical professionalism

No disponible

[Cardiovascular risk of cyclooxygenase selective inhibitors]. / Riesgo cardiovascular derivado de los inhibidores selectivos de la ciclooxigenasa.

It has been estimated that 30 million people worldwide take an nonsteroidal antiinflammatory drug (NSAID) daily. The main clinical objectives of these drugs are both to reduce joint pain and to improve joint function. However, gastrointestinal adverse events lead to the development of cyclooxygenase selective inhibitors (COXIB) with a better gastrointestinal safety profile. Since 1999, COXIB shown capacity to develop cardiovascular adverse events. Subsequent discoveries confirm overall risk of cardiovascular events. The increased cardiovascular risk occurred both in patients who were taking aspirin and in those who were not. Similar results with different COXIB appears to be a class effect of the COX-2 inhibitors, so patient risk factors must be identified and used in treatment decision making. Patients with gastrointestinal risk factors and no cardiovascular risk may benefit from use of a gastroprotective agent plus a nonselective nonsteroidal antiinflammatory drugs as a COXIB. We review assays whose objective was to study cardiovascular security of nonsteroidal antiinflammatory drugs and COXIB for known advantages and limitations of these drugs.

Bromocriptine during pregnancy in systemic lupus erythematosus: a pilot clinical trial.

Bromocriptine (BRC) prevents postpartum flare in lupus patients. However, its potential role in protecting lupus pregnancy from maternal-fetal complications has not been studied. The objective of the study was to explore the role of oral BRC during pregnancy in patients with systemic lupus erythematosus (SLE). Pregnant SLE patients were randomized into two groups: group 1 received BRC 2.5 mg/day and prednisone 10 mg/day; group 2 received prednisone 10 mg/day. These treatments were administered from 25 to 35 weeks of gestation. Prolactin (PRL) levels were determined at 25, 30, and 35 weeks. The SLE Pregnancy Disease Activity Index, maternal-fetal outcome including preterm birth, fetal loss, premature rupture of membrane (PRM), low birth weight, and preeclampsia/eclampsia were evaluated. We studied 20 patients (10 in each group). A significant decrease of PRL levels in group 1 compared to group 2 at week 30 and at week 35 was found. No patients in the BRC group had flares and three from group 2 had SLE activity. None of the patients in group 1 had PRM but three patients in group 2 did. Eighty percent of pregnancies ended in birth at term in group 1 and 50% in group 2. There was no fetal loss in both groups. Mean birth weight was higher in group 1 than in group 2 (P < NS). BRC was well tolerated. This is the first clinical trial of BRC in SLE pregnancy. Our pilot study suggests that BRC may play a role in the prevention of maternal-fetal complications, such as PRM, preterm birth, and active disease.

Tratamiento inmunosupresor en pacientes con glomerulonefritis lúpica. Revisión de eventos adversos / Immunosuppresive treatment in patients with lupus glomerulonephritis. Review of adverse events

El pronóstico de la nefritis lúpica ha mejorado notablemente en las últimas décadas, debido al mejor conocimiento de la patogenia e historial natural de la enfermedad, mejores esquemas terapéuticos y a la disponibilidad de nuevos fármacos para las enfermedades intercurrentes. La ciclofosfamida (CFM) se considera aún la mejor alternativa terapéutica inicial para la nefritis proliferativa, si bien aún existe controversia en relación al mejor esquema de dosificación, duración del tratamiento y terapia de mantenimiento después de la inducción. Sin embargo, para el médico y el paciente son motivo de gran preocupación la presencia de eventos adversos tales como las infecciones graves, neoplasias o amenorrea permanente. Para los casos resistentes al tratamiento, se pueden considerar nuevos inmunosupresores y agentes inmunoablativos, análogos de nucleósidos y terapia biológica. En todos estos casos, sin embargo, será necesario contar con estudios a largo plazo que verifiquen que estos nuevos tratamientos, con satisfactoria respuesta inicial, mantengan la respuesta y con menores efectos secundarios(AU)

The prognosis of lupus nephritis has improved significantly over the past few decades. This has been partly contributed to by a better understanding of the natural history of the disease, improved treatment regimens, and the use of adjunctive treatments. Despite the development of new modalities, cyclophosphamide (CYC) remains the preferred initial treatment for severe proliferative lupus nephritis. Controversies continue about the best route, dosage, and duration of CYC treatment. However, adverse events as major infections, neoplasia and permanent amenorrhea, remain as a great concern for physicians and patients. For recalcitrant disease, new immunosuppresive and immunomodulating agents, nucleoside analogues and the biological response modifiers can be considered. New treatments directed against more specific targets may theoretically be associated with higher efficacy and lower toxicity. Longterm studies are needed with new treatments to verify this assumed lower toxicity(AU)

[Immunosuppresive treatment in patients with lupus glomerulonephritis. Review of adverse events]. / Tratamiento inmunosupresor en pacientes con glomerulonefritis lúpica. Revisión de eventos adversos.

The prognosis of lupus nephritis has improved significantly over the past few decades. This has been partly contributed to by a better understanding of the natural history of the disease, improved treatment regimens, and the use of adjunctive treatments. Despite the development of new modalities, cyclophosphamide (CYC) remains the preferred initial treatment for severe proliferative lupus nephritis. Controversies continue about the best route, dosage, and duration of CYC treatment. However, adverse events as major infections, neoplasia and permanent amenorrhea, remain as a great concern for physicians and patients. For recalcitrant disease, new immunosuppresive and immunomodulating agents, nucleoside analogues and the biological response modifiers can be considered. New treatments directed against more specific targets may theoretically be associated with higher efficacy and lower toxicity. Longterm studies are needed with new treatments to verify this assumed lower toxicity.