Intravesical rAd-IFNα/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin-Refractory or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase II Randomized Study.

Purpose Many patients with high-risk non-muscle-invasive bladder cancer (NMIBC) are either refractory to bacillus Calmette-Guerin (BCG) treatment or may experience disease relapse. We assessed the efficacy and safety of recombinant adenovirus interferon alfa with Syn3 (rAd-IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG-refractory or relapsed NMIBC. Methods In this open-label, multicenter (n = 13), parallel-arm, phase II study ( ClinicalTrials.gov identifier: NCT01687244), 43 patients with HG BCG-refractory or relapsed NMIBC received intravesical rAd-IFNα/Syn3 (randomly assigned 1:1 to 1 × 10(11) viral particles (vp)/mL or 3 × 10(11) vp/mL). Patients who responded at months 3, 6, and 9 were retreated at months 4, 7, and 10. The primary end point was 12-month HG recurrence-free survival (RFS). All patients who received at least one dose were included in efficacy and safety analyses. Results Forty patients received rAd-IFNα/Syn3 (1 × 10(11) vp/mL, n = 21; 3 × 10(11) vp/mL, n = 19) between November 5, 2012, and April 8, 2015. Fourteen patients (35.0%; 90% CI, 22.6% to 49.2%) remained free of HG recurrence 12 months after initial treatment. Comparable 12-month HG RFS was noted for both doses. Of these 14 patients, two experienced recurrence at 21 and 28 months, respectively, after treatment initiation, and one died as a result of an upper tract tumor at 17 months without a recurrence. rAd-IFNα/Syn3 was well tolerated; no grade four or five adverse events (AEs) occurred, and no patient discontinued treatment because of an adverse event. The most frequently reported drug-related AEs were micturition urgency (n = 16; 40%), dysuria (n = 16; 40%), fatigue (n = 13; 32.5%), pollakiuria (n = 11; 28%), and hematuria and nocturia (n = 10 each; 25%). Conclusion rAd-IFNα/Syn3 was well tolerated. It demonstrated promising efficacy for patients with HG NMIBC after BCG therapy who were unable or unwilling to undergo radical cystectomy

Assessing Adverse Events in Madeira Primary

In last three decades, several epidemiological studies have been developed in order to assess the magnitude, nature and type of adverse events (AEs). Most of these studies focus on hospital settings, where the activities are more standardised, but imultaneously more complex and involving higher risks. However, in the last years, there is a growing movement and strong evidence that point out the importance of studying other healthcare contexts, such as primary care and long-term care. In Portugal, studies on primary care setting are scarce and still in the early stages. In this article, the authors describe the AEs assessment in Portuguese Primary Health Care (PHC) units in Madeira Island/Portugal. This study was quantitative, cross-sectional, observational and analytical, with probability sampling. We quantify and analyse the AEs registered by healthcare providers using the APEAS-PT formulary. A link to the APEAS–PT form was sent to 520 healthcare professionals (111 specialist in Family Medicine, 27 medical students, 382 nurses) who worked in 32 PHC centres. These professionals identified and analysed 85 AEs and 42 incidents, which corresponds to a prevalence of 3.9 AEs per 10,000 visits,with a 95% confidence interval (CI) between 3.7 and 4 AE. Most of the AEs were preventable (96%). The most frequent causal factors of AEs were associated with medication (69%), health care provided to users (54%), communication (41%) and diagnosis (22%). This analysis of AEs in Madeira island PHC contributed to reinforce patient safety culture and to better understand quaternary prevention.info:eu-repo/semantics/publishedVersio

Constraints on possible phase transitions above the nuclear saturation density

We compare different models for hadronic and quark phases of cold baryon-rich matter in an attempt to find a deconfinement phase transition between them. For the hadronic phase we consider Walecka-type mean-field models which describe well the nuclear saturation properties. We also use the variational chain model which takes into account correlation effects. For the quark phase we consider the MIT bag model, the Nambu-Jona-Lasinio and the massive quasiparticle models. By comparing pressure as a function of baryon chemical potential we find that crossings of hadronic and quark branches are possible only in some exceptional cases while for most realistic parameter sets these branches do not cross at all. Moreover, the chiral phase transition, often discussed within the framework of QCD motivated models, lies in the region where the quark phases are unstable with respect to the hadronic phase. We discuss possible physical consequences of these findings.Comment: 28 pages, 18 PostScript figures, submitted to Phys. Rev.

Exposure to animals and risk of oligoarticular juvenile idiopathic arthritis: a multicenter case-control study

<p>Abstract</p> <p>Background</p> <p>An inverse association between early contact with microbial compounds and respiratory allergies is well established. The protective effect of infant contact with animals was also shown for inflammatory bowel disease (IBD) and systemic lupus erythematosus (SLE). We aimed to test the association between animal contact in infancy and oligoarticular juvenile idiopathic arthritis (OA JIA).</p> <p>Methods</p> <p>Parents of children with OA JIA registered at the Hospital for Pediatric Rheumatology in Garmisch-Partenkirchen were asked to complete a questionnaire. Children who underwent strabismus surgery at six referral centers for ophthalmology served as controls. Children age 6 to 18 years born in Germany without malformations were included (238 cases; response 89% and 832 controls; response 86%). Data were analyzed using logistic regression models after adjusting for potential confounders.</p> <p>Results</p> <p>Neither place of living (urban vs. rural area), living on a farm, nor regular farm animal (adjusted odds ratio 0.79; 95% confidence interval 0.42-1.47) or pet contact (0.79; 0.55-1.14) during infancy were clearly related to case status. Allergic rhinitis was inversely related to OA JIA (0.57; 0.34-0.95).</p> <p>Neither place of living (urban vs. rural area), living on a farm, nor regular farm animal (adjusted odds ratio 0.79; 95% confidence interval 0.42-1.47) or pet contact (0.79; 0.55-1.14) during infancy were related to case status. Allergic rhinitis was inversely related to OA JIA (0.57; 0.34-0.95).</p> <p>Conclusions</p> <p>Contact with farm environments in infancy might not be associated with OA JIA. This finding is consistent with previous findings for diabetes mellitus type 1 but contradicts results for IBD and SLE.</p

Killer immunoglobulin-like receptor and human leukocyte antigen-C genotypes in rheumatoid arthritis primary responders and non-responders to anti-TNF-α therapy

The identification of patients who will respond to anti-tumor necrosis factor alpha (anti-TNF-α) therapy will improve the efficacy, safety, and economic impact of these agents. We investigated whether killer cell immunoglobulin-like receptor (KIR) genes are related to response to anti-TNF-α therapy in patients with rheumatoid arthritis (RA). Sixty-four RA patients and 100 healthy controls were genotyped for 16 KIR genes and human leukocyte antigen-C (HLA-C) group 1/2 using polymerase chain reaction sequence-specific oligonucleotide probes (PCR-SSOP). Each patient received anti-TNF-α therapy (adalimumab, etanercept, or infliximab), and clinical responses were evaluated after 3 months using the disease activity score in 28 joints (DAS28). We investigated the correlations between the carriership of KIR genes, HLA-C group 1/2 genes, and clinical data with response to therapy. Patients responding to therapy showed a significantly higher frequency of KIR2DS2/KIR2DL2 (67.7% R vs. 33.3% NR; P = 0.012). A positive clinical outcome was associated with an activating KIR–HLA genotype; KIR2DS2(+)HLA-C group 1/2 homozygous. Inversely, non-response was associated with the relatively inhibitory KIR2DS2(–)HLA-C group 1/2 heterozygous genotype. The KIR and HLA-C genotype of an RA patient may provide predictive information for response to anti-TNF-α therapy

Recommended practices for computerized clinical decision support and knowledge management in community settings: a qualitative study

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to identify recommended practices for computerized clinical decision support (CDS) development and implementation and for knowledge management (KM) processes in ambulatory clinics and community hospitals using commercial or locally developed systems in the U.S.</p> <p>Methods</p> <p>Guided by the Multiple Perspectives Framework, the authors conducted ethnographic field studies at two community hospitals and five ambulatory clinic organizations across the U.S. Using a Rapid Assessment Process, a multidisciplinary research team: gathered preliminary assessment data; conducted on-site interviews, observations, and field surveys; analyzed data using both template and grounded methods; and developed universal themes. A panel of experts produced recommended practices.</p> <p>Results</p> <p>The team identified ten themes related to CDS and KM. These include: 1) workflow; 2) knowledge management; 3) data as a foundation for CDS; 4) user computer interaction; 5) measurement and metrics; 6) governance; 7) translation for collaboration; 8) the meaning of CDS; 9) roles of special, essential people; and 10) communication, training, and support. Experts developed recommendations about each theme. The original Multiple Perspectives framework was modified to make explicit a new theoretical construct, that of Translational Interaction.</p> <p>Conclusions</p> <p>These ten themes represent areas that need attention if a clinic or community hospital plans to implement and successfully utilize CDS. In addition, they have implications for workforce education, research, and national-level policy development. The Translational Interaction construct could guide future applied informatics research endeavors.</p

Cinema-going trajectories in the digital age

The activity of cinema-going constantly evolves and gradually integrates the use of digital data and platforms to become more engaging for the audiences. Combining methods from the fields of Human Computer Interaction and Film Studies, we conducted two workshops seeking to understand cinema audiences’ digital practices and explore how the contemporary cinema-going experience is shaped in the digital age. Our findings suggest that going to the movies constitutes a trajectory during which cinemagoers interact with multiple digital platforms. At the same time, depending on their choices, they construct unique digital identities that represent a set of online behaviours and rituals that cinemagoers adopt before, while and after cinema-going. To inform the design of new, engaging cinemagoing experiences, this research establishes a preliminary map of contemporary cinema-going including digital data and platforms. We then discuss how audiences perceive the potential improvement of the experience and how that would lead to the construction of digital identities

It is time to talk about people: a human-centered healthcare system

Examining vulnerabilities within our current healthcare system we propose borrowing two tools from the fields of engineering and design: a) Reason's system approach [1] and b) User-centered design [2,3]. Both approaches are human-centered in that they consider common patterns of human behavior when analyzing systems to identify problems and generate solutions. This paper examines these two human-centered approaches in the context of healthcare. We argue that maintaining a human-centered orientation in clinical care, research, training, and governance is critical to the evolution of an effective and sustainable healthcare system

Latitude gradient influences the age of onset of rheumatoid arthritis : a worldwide survey

The age of onset of rheumatoid arthritis (RA) is an important outcome predictor. Northern countries report an age of RA onset of around 50 years, but apparently, variability exists across different geographical regions. The objective of the present study is to assess whether the age of onset of RA varies across latitudes worldwide. In a proof-of-concept cross-sectional worldwide survey, rheumatologists from preselected cities interviewed 20 consecutive RA patients regarding the date of RA onset (RAO, when the patient first noted a swollen joint). Other studied variables included location of each city, rheumatologist settings, latitudes (10A degrees increments, south to north), longitudes (three regions), intracountry consistency, and countries' Inequality-adjusted Human Development Index (IHDI). Data from 2481 patients (82% females) were obtained from 126 rheumatologists in 77 cities of 41 countries. Worldwide mean age of RAO was 44 +/- 14 years (95% CI 44-45). In 28% of patients, RA began before age 36 years and before age 46 years in 50% of patients. RAO was 8 years earlier around the Tropic of Cancer when compared with northern latitudes (p <0.001, 95% CI 3.5-13). Multivariate analysis showed that females, western cities, and latitudes around the Tropic of Cancer are associated with younger age of RAO (R (2) 0.045, p <0.001). A positive correlation was found between the age of RAO and IHDI (r = 0.7, p <0.01, R (2) 0.5). RA often begins at an early age and onset varies across latitudes worldwide. We postulate that countries' developmental status and their geographical and geomagnetic location influence the age of RAO.Peer reviewe