Public preferences on written informed consent for low-risk pragmatic clinical trials in Spain

Aims: Pragmatic randomized clinical trials (pRCTs) collect data that have the potential to improve medical care significantly. However, these trials may be undermined by the requirement to obtain written informed consent, which can decrease accrual and increase selection bias. Recent data suggest that the majority of the US public endorses written consent for low-risk pRCTs. The present study was designed to assess whether this view is specific to the US. Methods: The study took the form of a cross-sectional, probability-based survey, with a 2 × 2 factorial design, assessing support for written informed consent vs. verbal consent or general notification for two low-risk pRCTs in hypertension, one comparing two drugs with similar risk/benefit profiles and the other comparing the same drug being taken in the morning or at night. The primary outcome measures were respondents' personal preference and hypothetical recommendation to a research ethics committee regarding the use of written informed consent vs. the alternatives. Results: A total of 2008 adults sampled from a probability-based online panel responded to the web-based survey conducted in May 2016 (response rate: 61%). Overall, 77% of respondents endorsed written consent. In both scenarios, the alternative of general notification received significantly more support (28.7–37.1%) than the alternative of verbal consent (12.7–14.0%) (P = 0.001). Forty per cent of respondents preferred and/or recommended general notification rather than written consent. Conclusions: The results suggested that, rather than attempting to waive written consent, current pRCTs should focus on developing ways to implement written consent that provide sufficient information without undermining recruitment or increasing selection bias. The finding that around 40% of respondents endorsed general notification over written consent raises the possibility that, with educational efforts, the majority of Spaniards might accept general notification for low-risk pRCTsThis work was supported in part by the Victor Grifols i Lucas Foundation (Barcelona, Spain:http://www.fundaciogrifols.org/en/web/fundacio/home). The present work was funded in part by intramural research funds of the US NIH Clinical Cente

Wicked Problems and Gnarly Results: Reflecting on Design and Evaluation Methods for Idiosyncratic Personal Information Management Tasks

This paper is a case study of an artifact design and evaluation process; it is a reflection on how right thinking about design methods may at times result in sub-optimal results. Our goal has been to assess our decision making processthroughout the design and evaluation stages for a software prototype in order to consider where design methodology may need to be tuned to be more sensitive to the domain of practice, in this case software evaluation in personal information management. In particular, we reflect on design methods around (1) scale of prototype, (2) prototyping and design process, (3) study design, and (4) study population

Inverse Landau-Khalatnikov Transformation and Infrared Critical Exponents of (2+1)-dimensional Quantum Electrodynamics

By applying an inverse Landau-Khalatnikov transformation, connecting (resummed) Schwinger-Dyson treatments in non-local and Landau gauges of $QED_3$, we derive the infrared behaviour of the wave-function renormalization in the Landau gauge, and the associated critical exponents in the normal phase of the theory (no mass generation). The result agrees with the one conjectured in earlier treatments. The analysis involves an approximation, namely an expansion of the non-local gauge in powers of momenta in the infrared. This approximation is tested by reproducing the critical number of flavours necessary for dynamical mass generation in the chiral-symmetry-broken phase of $QED_3$.Comment: 13 pages LATEX, 1 Figure (included automatically

Identification of miR-379/miR-656 (C14MC) cluster downregulation and associated epigenetic and transcription regulatory mechanism in oligodendrogliomas

Introduction Although role of individual microRNAs (miRNAs) in the pathogenesis of gliomas has been well studied, their role as a clustered remains unexplored in gliomas. Methods In this study, we performed the expression analysis of miR-379/miR-656 miRNA-cluster (C14MC) in oligodendrogliomas (ODGs) and also investigated the mechanism underlying modulation of this cluster. Results We identified significant downregulation of majority of the miRNAs from this cluster in ODGs. Further data from The Cancer Genome Atlas (TCGA) also confirmed the global downregulation of C14MC. Furthermore, we observed that its regulation is maintained by transcription factor MEF2. In addition, epigenetic machinery involving DNA and histone-methylation are also involved in its regulation, which is acting independently or in synergy. The post- transcriptionally regulatory network of this cluster showed enrichment of key cancer-related biological processes such as cell adhesion and migration. Also, there was enrichment of several cancer related pathways viz PIK3 signaling pathway and glioma pathways. Survival analysis demonstrated association of C14MC (miR-487b and miR-409-3p) with poor progression free survival in ODGs. Conclusion Our work demonstrates tumor-suppressive role of C14MC and its role in pathogenesis of ODGs and therefore could be relevant for the development of new therapeutic strategies

Spiky Strings on I-brane

We study rigidly rotating strings in the near horizon geometry of the 1+1 dimensional intersection of two orthogonal stacks of NS5-branes, the so called I-brane background. We solve the equations of motion of the fundamental string action in the presence of two form NS-NS fluxes that the I-brane background supports and write down general form of conserved quantities. We further find out two limiting cases corresponding to giant magnon and single spike like strings in various parameter space of solutions.Comment: 17 pages, major restructuring of text, added a referenc

Impact of generic alendronate cost on the cost-effectiveness of osteoporosis screening and treatment

Introduction: Since alendronate became available in generic form in the Unites States in 2008, its price has been decreasing. The objective of this study was to investigate the impact of alendronate cost on the cost-effectiveness of osteoporosis screening and treatment in postmenopausal women. Methods: Microsimulation cost-effectiveness model of osteoporosis screening and treatment for U.S. women age 65 and older. We assumed screening initiation at age 65 with central dual-energy x-ray absorptiometry (DXA), and alendronate treatment for individuals with osteoporosis; with a comparator of "no screening" and treatment only after fracture occurrence. We evaluated annual alendronate costs of $20 through$800; outcome measures included fractures; nursing home admission; medication adverse events; death; costs; quality-adjusted life-years (QALYs); and incremental cost-effectiveness ratios (ICERs) in 2010 U.S. dollars per QALY gained. A lifetime time horizon was used, and direct costs were included. Base-case and sensitivity analyses were performed. Results: Base-case analysis results showed that at annual alendronate costs of $200 or less, osteoporosis screening followed by treatment was cost-saving, resulting in lower total costs than no screening as well as more QALYs (10.6 additional quality-adjusted life-days). When assuming alendronate costs of$400 through $800, screening and treatment resulted in greater lifetime costs than no screening but was highly cost-effective, with ICERs ranging from$714 per QALY gained through $13,902 per QALY gained. Probabilistic sensitivity analyses revealed that the cost-effectiveness of osteoporosis screening followed by alendronate treatment was robust to joint input parameter estimate variation at a willingness-to-pay threshold of$50,000/QALY at all alendronate costs evaluated. Conclusions: Osteoporosis screening followed by alendronate treatment is effective and highly cost-effective for postmenopausal women across a range of alendronate costs, and may be cost-saving at annual alendronate costs of $200 or less. © 2012 Nayak et al

A qualitative study of community pharmacists' opinions on the provision of osteoporosis disease state management services in Malaysia

Background: Osteoporosis has significant impact on healthcare costs and quality of life. Amongst the models for collaborative disease state management services published internationally, there is sparse evidence regarding the role of community pharmacists in the provision of osteoporosis care. Hence, the aim of our study was to explore community pharmacists' opinions (including the barriers and facilitators) and scope of osteoporosis disease state management services by community pharmacists in Malaysia, informing a vision for developing these services. Methods: Semi-structured individual interviews and focus groups discussions were conducted with community pharmacists from October 2013 to July 2014. Three trained researchers interviewed the participants. Interviews were recorded and transcribed verbatim. Data were analyzed thematically using an interpretative description approach. Results: Nineteen community pharmacists with 1-23 years of experience were recruited (in depth interviews: n = 9; focus group discussions: n = 10). These participants reflected on their experience with osteoporosis-related enquiries, which included medication counseling, bone density screening and referral of at-risk patients. Key barriers were the lack of numerous factors: public awareness of osteoporosis, accurate osteoporosis screening tools for community pharmacists, pharmacists' knowledge on osteoporosis disease and medications, time to counsel patients about bone health, collaboration between pharmacists and doctors, and support from the government and professional body. The pharmacists wanted more continuing education on osteoporosis, osteoporosis awareness campaigns, a simple, unbiased osteoporosis education material, and inter-professional collaboration practices with doctors, and pharmacists' reimbursement for osteoporosis care. Conclusions: The involvement of community pharmacists in the provision of osteoporosis disease state management was minimal. Only ad-hoc counseling on osteoporosis prevention was performed by community pharmacists. Development and trial of collaborative osteoporosis disease state management services in community pharmacy could be facilitated by training, support and remuneration

CAR-T cell. the long and winding road to solid tumors

Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host's defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles

Choroidal melanoma metastasizing to maxillofacial bones

BACKGROUND: Melanomas are malignant neoplasm of melanocytic origin, commonly seen on skin and various mucous membranes. Melanomas are the commonest intraocular malignant tumour in the adults. CASE PRESENTATION: A 50-year-old female presented with complains of painless progressive swelling in right cheek region of two months duration. Examination revealed a 6 × 4 cm bony hard swelling in right zygomatic region near and below lateral canthus of right eye with loss of vision. Investigations revealed it to be a choroidal melanoma metastatising to the zygomatic bone. Patient was successfully treated by surgery. CONCLUSION: Choroidal melanoma, which commonly metastasizes to liver and lungs, never involves the lymph nodes and metastasis to facial bones is rare. Here we report a case of choroidal melanoma metastasizing to maxillofacial bones