Subgroup analysis of a phase 2/3 study of rurioctocog alfa pegol in patients with severe hemophilia A: efficacy and safety in previously treated Korean patients

BACKGROUND: The efficacy and safety of extended half-life, full-length, pegylated recombinant factor VIII rurioctocog alfa pegol [BAX 855, ADYNOVATE (USA)/ADYNOVI (Europe); Baxalta US Inc., a Takeda company, Lexington, MA, USA] was investigated in previously treated Korean patients with severe hemophilia A (HA). METHODS: A post hoc data analysis from the international, multicenter, phase 2/3 PROLONG-ATE study of rurioctocog alfa pegol in patients with severe HA (NCT01736475) determined annualized bleeding rates (ABRs) and rates of adverse events (AEs) in Korean patients treated in this study. RESULTS: All 10 enrolled Korean patients receiving rurioctocog alfa pegol (9 prophylaxis, 1 on-demand) completed the study [median (range) age, 28.0 (12–50) yr; weight, 64.8 (45–90) kg; 8 patients had ≥1 target joint at screening]. Median (range) ABR was 1.9 (0.0–14.5) for patients on prophylaxis and 62.2 for the patient receiving on-demand treatment. The hemostatic efficacy of rurioctocog alfa pegol was rated “excellent” or “good” and only single infusions were required per bleeding episode. ABRs improved in most patients compared with prestudy values. No dose adjustments were required for prophylaxis, and the dosing frequency was reduced in 8 patients, compared with their previous prophylaxis regimen. No serious AEs were reported; all 9 nonserious AEs (in 3 patients) were mild in severity and unrelated to the study treatment. CONCLUSION: This post hoc analysis of a small group of Korean patients with severe HA indicated that rurioctocog alfa pegol was effective, and no serious AEs were observed. For most patients, the dosing frequency was also reduced compared with their previous regimen.

Paradigm Shift in the Study of Treatment Resistant Depression

Treatment-resistant depression (TRD) is a major public health problem. It is estimated that about 30% of patients with major depressive disorder do not show substantial clinical improvement to somatic or psychosocial treatment. Most of studies for TRD have focused on the subjects already known as TRD. Patients with unipolar depressive episodes that do not respond satisfactorily to numerous sequential treatment regimens were included in the TRD studies. Such post hoc experimental design can be regarded only as consequences of having TRD, rather than as causal risk factors for it. Although informative, data derived from such studies often do not allow a distinction to be made between cause and effect. So, we should shift paradigm toward examining the risk for developing TRD in untreated depressed patients. To deal with this problem, untreated depressed patients should be enrolled in the study to identify biological markers for treatment resistance. The peripheral or central biological markers should be explored before starting treatment. Subsequent systematic administration of treatments with appropriate monitoring in the subjects can determine the risk for developing treatment resistance in untreated individuals. Such information could give a cue to improve the initial diagnosis and provide more effective treatment for TRD.

Lukasiewicz logic based Fuzzy similarity classifier for Denver group chromosomal classification / Utilizando lógica de Lukasiewicz baseada em similaridade Fuzzy na classificação de cromossomos do tipo Denver group

This paper proposes a novel P1-weighted Lukasiewicz Logic based Fuzzy Similarity Classifier for classifying Denver Group of chromosomes and compares its performance with the other classifiers under study. A chromosome is classified to one of the seven groups from A to G, based on the Denver System of classification of chromosomes. Chromosomes within a particular Denver Group are difficult to identify, possessing almost identical characteristics for the extracted features. This work evaluates the performance of supervised classifiers including Naive Bayes, Support Vector Machine with Gaussian Kernel (SVM), Multilayer perceptron (MLP) and a novel, unsupervised, P1-weighted Lukasiewicz Logic based Fuzzy Similarity Classifier, in classifying the Denver Group of chromosomes. A fundamental review on fuzzy similarity based classification is presented. Experimental results clearly demonstrates that the proposed P1-weighted Lukasiewicz Logic based Fuzzy Similarity Classifier using the generalized Minkowski mean metric, produces the best classification results, almost identical to the Ground Truth values. One-way Analysis of Variance (ANOVA) at 95% and 99% level of confidence and Tukey's post-hoc analysis is performed to validate the selection of the classifier. The proposed P1-weighted Lukasiewicz Logic based Fuzzy Similarity Classifier gives the most promising classification results and can be applied to any large scale biomedical data and other applications.

Este trabalho propõe uma nova lógica P1pondera de Lukasiewicz de acordo com o classificador de similarida fuzzy para classificar cromossomas do Grupo Denver e compara o seu desempenho com os outros classificadores em estudo. Um cromossoma é classificado com um dos sete grupos de A a G, com base no Sistema de Denver de classificação de cromossomos. Cromossomos dentro de um grupo de Denver particular são difíceis de identificar, com características quase idênticas para os recursos extraídos. Este trabalho avalia o desempenho de classificadores supervisionados, incluindo Naive Bayes, Support Vector Machine com Gaussian Kernel (SVM), perceptron multicamadas (MLP) e um novo classificador sem supervisão, P1-weighted, lógica de Lukasiewicz de acordo com o classificador de similaridade Fuzzy para a classificação do Grupo Denver de cromossomos . Apresenta-se ma revisão fundamentada na classificação de acordo com similaridade difusa. Resultados experimentais demonstram claramente que Classificador Similaridade Fuzzy proposto de acordo com a lógica de Lukasiewicz P1-weighted usando a médica métrica de Minkowski para produz melhores resultados de classificação. Estes valores foram muito similares aos valores de Ground Truth . Análise de variancia (ANOVA) com 95% de grau de confiança e análise post-hoc de Tukey 99% foram realizadas para validar a seleção do classificador. Este classificador P1-weighted de lógica de Lukasiewicz está de acordo com o classificador de similaridade difusa oferecendo resultados declassificação mais promissoras. Portanto, podendo ser aplicado a dados biomédicos em larga escala além de outras aplicações.

F-18 Fluorodeoxyglucose PET/CT and Post Hoc PET/MRI in a Case of Primary Meningeal Melanomatosis

Primary meningeal melanomatosis is a rare, aggressive variant of primary malignant melanoma of the central nervous system, which arises from melanocytes within the leptomeninges and carries a poor prognosis. We report a case of primary meningeal melanomatosis in a 17-year-old man, which was diagnosed with 18F-fluorodeoxyglucose (F-18 FDG) PET/CT, and post hoc F-18 FDG PET/MRI fusion images. Whole-body F-18 FDG PET/CT was helpful in ruling out the extracranial origin of melanoma lesions, and in assessing the therapeutic response. Post hoc PET/MRI fusion images facilitated the correlation between PET and MRI images and demonstrated the hypermetabolic lesions more accurately than the unenhanced PET/CT images. Whole body F-18 FDG PET/CT and post hoc PET/MRI images might help clinicians determine the best therapeutic strategy for patients with primary meningeal melanomatosis.

La medicalización de los problemas sociales / Medicalization of social problems

El presente artículo analiza el tema de la medicalización de los problemas sociales como una extensión indebida del modelo médico. Esta medicalización tiene una triple consecuencia negativa que se caracteriza como: némesis metodológica, némesis clínica y némesis social. Se aportan ejemplos de la literatura médica contemporánea y se profundiza particularmente en la medicalización de la violencia social y en el abuso ideológico de la ciencia que esta demuestra tanto en el pasado como, lamentablemente, también en la actualidad.

The present article analyzed the topic of medicalization of social problems as an inappropriate extension of the medical model that brings about three negative consequences: methodological nemesis, clinical nemesis and social nemesis. Several examples were drawn from the current medical literature, with a special emphasis on the medicalization of social violence and the ideological misuse of science in the past and, unfortunately, at present.

The Appropriate Interpretation of Recent Clinical Trials: How to Read RCT in the Era of Advertizing-based Medicine

Although evidence-based medicine (EBM) has changed medical therapy from experience- or experiment-based medicine to the modern science-based medicine, nowadays it seems to be used as a tool of advertizing strategy of industries. Clinical trial is a fundamental component of EBM and it costs very much and are mostly conducted by the financial support of pharmaceutical industries at a tremendous expense. If anticipated results for the sponsor were not shown in the trial, a "spin" has been used to mislead readers as if positive results for test drugs or devices were obtained by emphasizing subgroup analysis, or searching favorable endpoint by post-hoc analysis. Clinical trials on angiotensin receptor blocker (ARB) are continuing succession of defeat all over world except two Japanese clinical trials, JIKEI HEART and KYOTO HEART studies. However, in both trials, subjective soft endpoints, such as angina pectoris or congestive heart failure were used despite of prospective randomized, open labeled, blinded endpoint design. In the era of advertizing-based medicine, It is important to read clinical trial data with critical view points.

Post-hoc Survey for Power of 119 Negative Results in Korean Journal of Anesthesiology / 대한마취과학회지

BACKGROUND: Statistical type II error has seemed to be ignored commonly by medical researchers. To control and present a power value could be helpful to reduce this type of error and to improve a quality of scientific decision making. We performed the post-hoc survey of the power of the negative results in Korean Journal of Anesthesiology (KJA). METHODS: One Hundred nineteen articles with negative results published in KJA during a year of 1997 were selected. We collected the numbers of the sample size and calculated the power of the given negative result only when applicable. And each author's attitude to negative results was taken by arbitrary criteria. RESULTS: Median sample size of these negative results was 16 12 (median interquartile range). We can calculate the power only in 43 articles of 119 negative results. Median power is 18.0% (interquartile range 26.0). In thirty six articles (83.8% of 43) the powers are proved to be under 80.0%. And 22 articles (51.2% of 43) have the powers even under 20.0%. We couldn't find any author who included either power or effect size in the article, and there was only one article in which its authors considered their inadequate number of sample size. CONCLUSIONS: We conclude that authors of KJA tend to ignore statistical type II error. In 119 negative results published in KJA during 1997, the calculated powers were very low and were not reported in the text.