Diversity in proof appraisal

We investigated whether mathematicians typically agree about the qualities of mathematical proofs. Between-mathematician consensus in proof appraisals is an implicit assumption of many arguments made by philosophers of mathematics, but to our knowledge the issue has not previously been empirically investigated. We asked a group of mathematicians to assess a specific proof on four dimensions, using the framework identified by Inglis and Aberdein (2015). We found widespread disagreement between our participants about the aesthetics, intricacy, precision and utility of the proof, suggesting that a priori assumptions about the consistency of mathematical proof appraisals are unreasonable

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Carfilzomib en el tratamiento de mieloma múltiple: revisión sistemática de la literatura y experiencia colombiana basada en RIPS / Carfilzomib for the Treatment of Multiple Myeloma: Systematic Review of the Literature and Colombian Experience Based on RIPS / Carfilzomib no tratamento do mieloma múltiplo: revisão da literatura e da experiência colombiana baseada em RIPS

Introducción: El mieloma múltiple es un tumor maligno y progresivo de las células B asociado a lesiones osteolíticas, inmunodeficiencia y disfunción renal que ha sido tratado desde 2008 con bortezomib con el cual se logró un aumento del tiempo de sobrevida de los pacientes, sin embargo su uso se vio limitado por efectos adversos dependientes de la dosis, en especial la neuropatía periférica dolorosa. Recientemente ha entrado en uso carfilzomib (agente inhibidor de proteosoma de segunda generación) aprobado por la FDA en 2012 como agente único para tratamiento de enfermedad refractaria y recaídas de mieloma múltiple. Objetivo: Realizar una revisión de la literatura y determinar la experiencia colombiana con el medicamento carfilzomib teniendo en cuenta las estadísticas nacionales consignadas en los registros individuales de prestación de servicios de salud. Además se describe la situación de un caso clínico. Metodología: La revisión se hizo con base en literatura indexada en PubMed; como criterio de inclusión se tuvo en cuenta que los artículos a revisar fueran estudios clínicos de fase 2 y 3 de carfilzomib en manejo de mieloma múltiple. Respecto a la experiencia colombiana se identificaron 37 pacientes colombianos con mieloma múltiple diagnosticado entre 2003 y 2012 y a quienes se hubiera prescrito carfilzomib, teniendo en cuenta información proporcionada por Biotoscana. Resultados: En total se localizaron 8 estudios clínicos con asignación al azar que evidencian efectos adversos no hematológicos como fatiga (367 de los 678 pacientes, 54%), y náusea (323 pacientes, 48%). En el caso de los RIPS, de los 37 pacientes, 22 pacientes recibieron de 1 a 8 ciclos de carfilzomib (promedio 3.0, mediana 3). Se evaluó la respuesta clínica en 9 de ellos, encontrándose 4 pacientes (22%) en respuesta parcial muy buena, 4 pacientes (22%) en respuesta parcial, 1 paciente (6%) con enfermedad estable. Conclusiones: Se encontró diferencia entre los efectos adversos que se reportan en Colombia y los que se han reportado globalmente, predominando en nuestros pacientes la fatiga; asimismo se concluye que la experiencia con nuevos medicamentos no ha sido suficientemente documentada. [Castañeda C, Pantoja MC, Montaño L, Rosselli D. Carfilzomib en el tratamiento de mieloma múltiple: revisión sistemática de la literatura y experiencia colombiana basada en RIPS. MedUNAB 2015; 17(2):X:X] Introduction: Multiple myeloma is a B-cell malignant and progressive tumor, associated with osteolytic lesions, immunodeficiency and renal dysfunction, that has been treated since 2008 with Bortezomib, which achieved an increase in patients survival, however its use was limited due to dose dependent adverse effects, especially painful peripheral neuropathy, it has recently come into use Carfilzomib (a second generation proteasome inhibitor agent) approved by the FDA in 2012 as the only agent for treatment of refractory disease and relapsing of multiple myeloma. Objective: To conduct a literature review and determine the Colombian experience with the drug Carfilzomib, considering national statistics contained in the individual records of health service delivery, plus the status of a case is described. Methodology: for the review was considered literature indexed in PubMed, as an inclusion criterion was considered clinical studies Phase 2 and 3 that reviewed Carfilzomib in handling multiple myeloma. Regarding the Colombian experience, taking information provided by Biotoscana, 37 multiple myeloma Colombian patients diagnosed between 2003 and 2012 and who had been prescribed Carfilzomib were identified. Results: A total of eight randomized trials shown on hematologic adverse effects such as fatigue (367 of 678 patients, 54%), and nausea (323 patients, 48%). For the RIPS of 37 patients, 22 patients received 1 to 8 cycles Carfilzomib (3.0 average, median 3). Clinical response in 9 of them, 4 patients (22%) very good partial response, 4 patients (22%) partial response, 1 patient (6%) with stable disease was assessed. Conclusions: We found difference between the side effects reported in Colombia from the ones who have been reported globally, fatigue prevails in our patients, also experience with new drugs has not been sufficiently documented. [Castañeda C, Pantoja MC, Montaño L, Rosselli D. Carfilzomib for the Treatment of Multiple Myeloma: Systematic Review of the Literature and Colombian Experience Based on RIPS. MedUNAB 2015; 17(2):X:X] Introdução: O mieloma múltiplo é um tumor maligno e progressivo das células B associado com lesões osteolíticas, imunodeficiência e disfunção renal que tem sido tratados desde 2008 com bortezomib com o qual se conseguiu um aumento no tempo de sobrevida dos pacientes, entretanto a seu uso foi limitado pelos efeitos colaterais dose dependente, especialmente a neuropatia periférica dolorosa. Recentemente se introduziu o uso Carfilzomib (agente inibidor do proteosoma de segunda geração), aprovado pelo FDA em 2012 como única droga para o tratamento da doença refratária e recidiva do mieloma múltiplo. Objetivo: Realizar revisão da literatura e determinar a experiência colombiana com a droga Carfilzomib considerando as estatísticas nacionais contidas nos prontuários individuais de prestação de serviços de saúde, além de descrever um caso clínico. Metodologia: Para a revisão foi levantada a literatura indexada no PubMed, sendo o critério de inclusão os estudos clínicos de fase 2 e 3 de Carfilzomib no tratamento do mieloma múltiplo. Em relação a experiência colombiana, foram identificados 37 pacientes colombianos com mieloma múltiplo diagnosticado entre 2003 e 2012 e que foram submetidos a prescrição de Carfilzomib, levando em conta as informações fornecidas pela BIOTOSCANA. Resultados: Foram localizados 8 estudos clínicos randomizados que evidenciaram efeitos colaterais não hematológicos tais como fadiga (367 de 678 pacientes, 54%) e náuseas (323 pacientes, 48%). Para os RIPS, 22 dos 37 pacientes receberam de 1 a 8 ciclos de Carfilzomib (média=3,0, mediana=3). Foi avaliada a resposta clínica em 9 pacientes, sendo 4(22%) com resposta parcial muito boa, 4(22%) resposta parcial e 1 (6%) com doença estável. Conclusões: Encontramos diferença entre os efeitos colaterais relatados na Colômbia em relação aos relatados mundialmente, com predominância da fadiga em nossos pacientes e se conclue que a experiência com novas drogas não foi suficientemente documentada. [Castañeda C, Pantoja MC, Montaño L, Rosselli D. Carfilzomib no tratamento do mieloma múltiplo: revisão da literatura e da experiência colombiana baseada em RIPS. MedUNAB 2015; 17(2):X:X