Achievement of Remission Endpoints with Secukinumab Over 3 Years in Active Ankylosing Spondylitis: Pooled Analysis of Two Phase 3 Studies

INTRODUCTION: Clinical remission in patients with ankylosing spondylitis (AS) has been determined using composite indices such as the AS Disease Activity Score inactive disease (ASDAS-ID), Assessment of SpondyloArthritis international Society criteria partial remission (ASAS-PR), and low Bath AS Disease Activity Index (BASDAI) scores. The objective of this exploratory analysis was to evaluate the proportion of secukinumab-treated patients with AS achieving remission defined based on the ASDAS-ID (score < 1.3), ASAS-PR or BASDAI score ≤  2. METHODS: The analysis pooled data from the MEASURE 1 and 2 studies over 3 years. The proportion of patients who achieved ASDAS-ID, ASAS-PR, or BASDAI ≤ 2 with secukinumab was compared with placebo at week 16; results for secukinumab-treated patients were summarized through week 156. Sustainability of each criterion was assessed from week 16 to 156 using shift analysis. The association between each of these criteria and specific patient-reported outcomes (PROs), such as health-related quality of life, function, fatigue, and work impairment, was also explored. RESULTS: At week 16, a higher proportion of secukinumab-treated patients versus placebo achieved ASDAS-ID (17.6 vs. 3.5%), ASAS-PR (15.4 vs. 4.1%), or BASDAI ≤ 2 (22.3 vs. 6.4%) criteria (all P < 0.0001), which were sustained through 156 weeks. Shift analysis showed that the majority of secukinumab-treated patients achieving remission at week 16 maintained their status at week 156 (ASDAS-ID, 57.1%; ASAS-PR, 68.0% and BASDAI ≤ 2, 74.3%). Remission was also associated with improved PROs over 156 weeks. CONCLUSIONS: Secukinumab-treated patients maintained ASDAS-ID, ASAS-PR, or BASDAI ≤ 2 from week 16 up to 3 years. Patients who achieved at least one of the three responses/states, reported improvement in PROs, which suggests an association of clinical remission/ID with PROs in patients with active AS. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01358175, NCT01863732, and NCT01649375

PET brain imaging in HIV-associated neurocognitive disorders (HAND) in the era of combination antiretroviral therapy

Effective combination antiretroviral therapy (cART) has lead to a significant reduction in the prevalence and incidence of central nervous system (CNS) HIV-associated brain disease, particularly CNS opportunistic infections and HIV encephalitis. Despite this, cognitive deficits in people living with HIV, also known as HIV-associated neurocognitive disorders (HAND) have become more prevalent in recent years. The pathogenesis of HAND is likely to be multifactorial, however recent evidence suggests that brain microglial activation is the most likely pathogenic mechanism. Recent developments in positron emission tomography (PET) brain neuroimaging using novel brain radioligands targeting a variety of physiological changes in the brains of HIV-positive individuals have improved our understanding of the mechanisms associated with the development of HAND. This review will highlight recent PET brain neuroimaging studies in the cART era, focusing on physiological and neurochemical changes associated with HAND in people living with HIV

Latent Patient Network Learning for Automatic Diagnosis

Recently, Graph Convolutional Networks (GCNs) has proven to be a powerful machine learning tool for Computer Aided Diagnosis (CADx) and disease prediction. A key component in these models is to build a population graph, where the graph adjacency matrix represents pair-wise patient similarities. Until now, the similarity metrics have been defined manually, usually based on meta-features like demographics or clinical scores. The definition of the metric, however, needs careful tuning, as GCNs are very sensitive to the graph structure. In this paper, we demonstrate for the first time in the CADx domain that it is possible to learn a single, optimal graph towards the GCN's downstream task of disease classification. To this end, we propose a novel, end-to-end trainable graph learning architecture for dynamic and localized graph pruning. Unlike commonly employed spectral GCN approaches, our GCN is spatial and inductive, and can thus infer previously unseen patients as well. We demonstrate significant classification improvements with our learned graph on two CADx problems in medicine. We further explain and visualize this result using an artificial dataset, underlining the importance of graph learning for more accurate and robust inference with GCNs in medical applications

Predicting Distribution of Aedes Aegypti and Culex Pipiens Complex, Potential Vectors of Rift Valley Fever Virus in Relation to Disease Epidemics in East Africa.

The East African region has experienced several Rift Valley fever (RVF) outbreaks since the 1930s. The objective of this study was to identify distributions of potential disease vectors in relation to disease epidemics. Understanding disease vector potential distributions is a major concern for disease transmission dynamics. DIVERSE ECOLOGICAL NICHE MODELLING TECHNIQUES HAVE BEEN DEVELOPED FOR THIS PURPOSE: we present a maximum entropy (Maxent) approach for estimating distributions of potential RVF vectors in un-sampled areas in East Africa. We modelled the distribution of two species of mosquitoes (Aedes aegypti and Culex pipiens complex) responsible for potential maintenance and amplification of the virus, respectively. Predicted distributions of environmentally suitable areas in East Africa were based on the presence-only occurrence data derived from our entomological study in Ngorongoro District in northern Tanzania. Our model predicted potential suitable areas with high success rates of 90.9% for A. aegypti and 91.6% for C. pipiens complex. Model performance was statistically significantly better than random for both species. Most suitable sites for the two vectors were predicted in central and northwestern Tanzania with previous disease epidemics. Other important risk areas include western Lake Victoria, northern parts of Lake Malawi, and the Rift Valley region of Kenya. Findings from this study show distributions of vectors had biological and epidemiological significance in relation to disease outbreak hotspots, and hence provide guidance for the selection of sampling areas for RVF vectors during inter-epidemic periods

A New Chanidae (Ostariophysii: Gonorynchiformes) from the Cretaceous of Brazil with Affinities to Laurasian Gonorynchiforms from Spain

Based on specimens originally referred to as “Dastilbe minor”, a nomem-nudum, we describe a new genus of Chanidae †Nanaichthys longipinnus nov. gen. and sp. which exhibits several diagnostic characters such as the absence of orbitosphenoid and basisphenoid, anteriorly displaced quadrate-mandibular articulation, laterally expanded supraneurals, an acute angle between the preopercular limbs, expansion at the angle between the preopercular limbs, and a curved maxillary articular process. Its occurrence and supposed relationship within the Chanidae reinforce the influence of the Mediterranean Tethys over the Gondwanan main rift system prior to the Aptian/Albian highstands

Health and Sickness Absence in Denmark: A Study of Elderly-Care Immigrant Workers

The objective of this study is to investigate patterns of sickness absence in light of health status among immigrants. Cross-sectional data from 2005 was used and the study population consisted of 3,121 healthcare assistants and healthcare helpers working in the elderly-care sector in Denmark. A multinomial logistic regression was employed to investigate the relationship between health indicator, sickness absence and being an immigrant. Our findings show that, on one hand, immigrants have worse health status, but on the other, they have significantly lower sickness absence than their Danish counterparts, even after factors such as age and gender are controlled for. The results show that the relationship between being an immigrant and sickness absence differs according to health status. Our findings are in line with Steer and Rhode’s theoretical framework, according to which attendance to work is a function of ability and motivation to be at work

The Antioxidant Potential of the Mediterranean Diet in Patients at High Cardiovascular Risk: An In-Depth Review of the PREDIMED

Cardiovascular disease (CVD) is the leading global cause of death. Diet is known to be important in the prevention of CVD. The PREDIMED trial tested a relatively low-fat diet versus a high-fat Mediterranean diet (MedDiet) for the primary prevention of CVD. The resulting reduction of the CV composite outcome resulted in a paradigm shift in CV nutrition. Though many dietary factors likely contributed to this effect, this review focuses on the influence of the MedDiet on endogenous antioxidant systems and the effect of dietary polyphenols. Subgroup analysis of the PREDIMED trial revealed increased endogenous antioxidant and decreased pro-oxidant activity in the MedDiet groups. Moreover, higher polyphenol intake was associated with lower incidence of the primary outcome, overall mortality, blood pressure, inflammatory biomarkers, onset of new-onset type 2 diabetes mellitus (T2DM), and obesity. This suggests that polyphenols likely contributed to the lower incidence of the primary event in the MedDiet groups. In this article, we summarize the potential benefits of polyphenols found in the MedDiet, specifically the PREDIMED cohort. We also discuss the need for further research to confirm and expand the findings of the PREDIMED in a non-Mediterranean population and to determine the exact mechanisms of action of polyphenols

Radiographers supporting radiologists in the interpretation of screening mammography: a viable strategy to meet the shortage in the number of radiologists.

BackgroundAn alternative approach to the traditional model of radiologists interpreting screening mammography is necessary due to the shortage of radiologists to interpret screening mammograms in many countries.MethodsWe evaluated the performance of 15 Mexican radiographers, also known as radiologic technologists, in the interpretation of screening mammography after a 6 months training period in a screening setting. Fifteen radiographers received 6 months standardized training with radiologists in the interpretation of screening mammography using the Breast Imaging Reporting and Data System (BI-RADS) system. A challenging test set of 110 cases developed by the Breast Cancer Surveillance Consortium was used to evaluate their performance. We estimated sensitivity, specificity, false positive rates, likelihood ratio of a positive test (LR+) and the area under the subject-specific Receiver Operating Characteristic (ROC) curve (AUC) for diagnostic accuracy. A mathematical model simulating the consequences in costs and performance of two hypothetical scenarios compared to the status quo in which a radiologist reads all screening mammograms was also performed.ResultsRadiographer's sensitivity was comparable to the sensitivity scores achieved by U.S. radiologists who took the test but their false-positive rate was higher. Median sensitivity was 73.3 % (Interquartile range, IQR: 46.7-86.7 %) and the median false positive rate was 49.5 % (IQR: 34.7-57.9 %). The median LR+ was 1.4 (IQR: 1.3-1.7 %) and the median AUC was 0.6 (IQR: 0.6-0.7). A scenario in which a radiographer reads all mammograms first, and a radiologist reads only those that were difficult for the radiographer, was more cost-effective than a scenario in which either the radiographer or radiologist reads all mammograms.ConclusionsGiven the comparable sensitivity achieved by Mexican radiographers and U.S. radiologists on a test set, screening mammography interpretation by radiographers appears to be a possible adjunct to radiologists in countries with shortages of radiologists. Further studies are required to assess the effectiveness of different training programs in order to obtain acceptable screening accuracy, as well as the best approaches for the use of non-physician readers to interpret screening mammography