COVID-19 in multiple sclerosis and neuromyelitis optica spectrum disorder patients in Latin America: COVID-19 in MS and NMOSD patients in LATAM.

BACKGROUND: There is no data regarding COVID-19 in Multiple Sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) patients in Latin America. OBJECTIVE: The objective of this study was to describe the clinical characteristics and outcomes of patients included in RELACOEM, a LATAM registry of MS and NMOSD patients infected with COVID-19. METHODS: RELACOEM is a longitudinal, strictly observational registry of MS and NMOSD patients who suffer COVID-19 and Dengue in LATAM. Inclusion criteria to the registry were either: (1) a biologically confirmed COVID-19 diagnosis based on a positive result of a COVID-19 polymerase chain reaction (PCR) test on a nasopharyngeal swab; or (2) COVID-19-typical symptoms (triad of cough, fever, and asthenia) in an epidemic zone of COVID-19. Descriptive statistics were performed on demographic and clinical variables. The cohort was later stratified for MS and NMOSD and univariate and multivariate logistic regression analysis was performed to identify variables associated with hospitalizations/intensive critical units (ICU) admission. RESULTS: 145 patients were included in the registry from 15 countries and 51 treating physicians. A total of 129 (89%) were MS patients and 16 (11%) NMOSD. 81.4% patients had confirmed COVID-19 and 18.6% were suspected cases. 23 (15.8%) patients were hospitalized, 9 (6.2%) required ICU and 5 (3.4 %) died due to COVID-19. In MS patients, greater age (OR 1.17, 95% CI 1.05 - 1.25) and disease duration (OR 1.39, 95%CI 1.14-1.69) were associated with hospitalization/ICU. In NMOSD patients, a greater age (54.3 vs. 36 years, p=<0.001), increased EDSS (5.5 vs 2.9, p=0.0012) and disease duration (18.5 vs. 10.3 years, p=0.001) were significantly associated with hospitalization/ICU. CONCLUSION: we found that in MS patients, age and disease duration was associated with hospitalization and ICU admission requirement, while age, disease duration and EDSS was associated in NMOSD.

Consenso venezolano para el uso de la resonancia magnética en el diagnóstico y seguimiento de pacientes con esclerosis múltiple / Venezuelan consensus guidelines on the use of magnetic resonance in diagnosis and follow up of patients with multiple sclerosis

Introducción. El uso de la resonancia magnética (RM) en el diagnóstico y seguimiento de pacientes con esclerosis múltiple (EM) se ha incrementado considerablemente durante los últimos años. Diversos grupos de trabajo internacionales han intentado clarificar y normativizar el uso de la RM tanto en el momento del diagnóstico como durante el seguimiento de los pacientes. Sin embargo, en muchas ocasiones se extrapolan datos de otras regiones que no contemplan la realidad de cada lugar o son difíciles de implementar. Objetivo. Elaborar un consenso venezolano para el uso de la RM en el diagnóstico y seguimiento de pacientes con EM. Desarrollo. Un grupo de expertos de Venezuela, conformado por neurólogos y radiólogos, mediante metodología de ronda de encuestas a distancia y reuniones presenciales, llevó adelante la elaboración del consenso pretendido para el uso de la RM en el diagnóstico y seguimiento de pacientes con EM en Venezuela. Se establecieron 17 recomendaciones basadas en la evidencia publicada y en el criterio de los expertos que participaron. Las recomendaciones se enfocaron en el papel de las técnicas convencionales de RM, así como en el de la medición de la atrofia cerebral en pacientes con EM, tanto en el momento del diagnóstico como durante el seguimiento. Conclusión. Las recomendaciones establecidas en el presente consenso permitirán optimizar el cuidado y el seguimiento de los pacientes con EM en Venezuela (AU)

Introduction. The clinical use of magnetic resonance (MR) in patients with multiple sclerosis (MS) has advanced markedly over the past few years. Several groups around the world have developed consensus guidelines about the role of MR in MS at diagnosis and during follow up. However, in some regions is difficult to extrapolate the recommendations. Aim. To provide recommendations for the implementation of MR in MS patients at diagnosis and follow up in Venezuela. Development. A group of experts from Venezuela that included neurologists and radiologists, by using the online surveys methodology as well as face to face meetings developed the intended consensus for the use of MR during the diagnosis and follow up of MS patients in Venezuela. Seventeen recommendations were established based on published evidence and the expert opinion. Recommendations focused on the role of conventional MR techniques and brain atrophy measurement in MS patients both at diagnosis and during follow-up. Conclusions. The recommendations of this consensus guidelines attempts to optimize the health care and management of patients with MS in Venezuela (AU)

Biological and nonbiological complex drugs for multiple sclerosis in Latin America: regulations and risk management.

Biological drugs and nonbiological complex drugs with expired patents are followed by biosimilars and follow-on drugs that are supposedly similar and comparable with the reference product in terms of quality, safety and efficacy. Unlike simple molecules that can be copied and reproduced, biosimilars and follow-on complex drugs are heterogeneous and need specific regulations from health and pharmacovigilance agencies. A panel of 14 Latin American experts on multiple sclerosis from nine different countries met to discuss the recommendations regarding biosimilars and follow-on complex drugs for treating multiple sclerosis. Specific measures relating to manufacturing, therapeutic equivalence assessment and pharmacovigilance reports need to be implemented before commercialization. Physical, chemical, biological and immunogenic characterizations of the new product need to be available before clinical trials start. The new product must maintain the same immunogenicity as the original. Automatic substitution of biological and complex drugs poses unacceptable risks to the patient.

Rifampicin reduces susceptibility to ofloxacin in rifampicin-resistant Mycobacterium tuberculosis through efflux.

RATIONALE: Central dogma suggests that rifampicin resistance in Mycobacterium tuberculosis develops solely through rpoB gene mutations. OBJECTIVE: To determine whether rifampicin induces efflux pumps activation in rifampicin resistant M. tuberculosis strains thereby defining rifampicin resistance levels and reducing ofloxacin susceptibility. METHODS: Rifampicin and/or ofloxacin minimum inhibitory concentrations (MICs) were determined in rifampicin resistant strains by culture in BACTEC 12B medium. Verapamil and reserpine were included to determine their effect on rifampicin and ofloxacin susceptibility. RT-qPCR was applied to assess expression of efflux pump/transporter genes after rifampicin exposure. To determine whether verapamil could restore susceptibility to first-line drugs, BALB/c mice were infected with a MDR-TB strain and treated with first-line drugs with/without verapamil. MEASUREMENTS AND MAIN FINDINGS: Rifampicin MICs varied independently of rpoB mutation and genetic background. Addition reserpine and verapamil significantly restored rifampicin susceptibility (p = 0.0000). RT-qPCR demonstrated that rifampicin induced differential expression of efflux/transporter genes in MDR-TB isolates. Incubation of rifampicin mono-resistant strains in rifampicin (2 µg/ml) for 7 days induced ofloxacin resistance (MIC > 2 µg/ml) in strains with an rpoB531 mutation. Ofloxacin susceptibility was restored by exposure to efflux pump inhibitors. Studies in BALB/c mice showed that verapamil in combination with first-line drugs significantly reduced pulmonary CFUs after 1 and 2 months treatment (p < 0.05). CONCLUSION: Exposure of rifampicin resistant M. tuberculosis strains to rifampicin can potentially compromise the efficacy of the second-line treatment regimens containing ofloxacin, thereby emphasising the need for rapid diagnostics to guide treatment. Efflux pump inhibitors have the potential to improve the efficacy of anti-tuberculosis drug treatment.