Dynamic consent: a patient interface for twenty-first century research networks

Biomedical research is being transformed through the application of information technologies that allow ever greater amounts of data to be shared on an unprecedented scale. However, the methods for involving participants have not kept pace with changes in research capability. In an era when information is shared digitally at the global level, mechanisms of informed consent remain static, paper-based and organised around national boundaries and legal frameworks. Dynamic consent (DC) is both a specific project and a wider concept that offers a new approach to consent; one designed to meet the needs of the twenty-first century research landscape. At the heart of DC is a personalised, digital communication interface that connects researchers and participants, placing participants at the heart of decision making. The interface facilitates two-way communication to stimulate a more engaged, informed and scientifically literate participant population where individuals can tailor and manage their own consent preferences. The technical architecture of DC includes components that can securely encrypt sensitive data and allow participant consent preferences to travel with their data and samples when they are shared with third parties. In addition to improving transparency and public trust, this system benefits researchers by streamlining recruitment and enabling more efficient participant recontact. DC has mainly been developed in biobanking contexts, but it also has potential application in other domains for a variety of purposes.     

Development of decellularized conjunctiva as a substrate for the ex vivo expansion of conjunctival epithelium

This study was performed to develop a method to decellularize human conjunctiva and to characterize the tissue in terms of its deoxyribose nucleic acid (DNA) content, tensile strength, collagen denaturation, basement membrane, extracellular matrix components and its potential to support conjunctival epithelial growth. Human conjunctival tissues were subjected to a decellularization process involving hypotonic detergent and nuclease buffers. Variations in sodium dodecyl sulfate concentration (0.05–0.5%, w/v) were tested to determine the appropriate concentration of detergent buffer. DNA quantification, collagen denaturation, cytotoxicity and tensile strength were investigated. Human conjunctival cell growth by explant culture on the decellularized tissue substrate was assessed after 28 days in culture. Samples were fixed and paraffin embedded for immunohistochemistry including conjunctival epithelial cell markers and extracellular matrix proteins. Conjunctival tissue from 20 eyes of 10 donors (age range 65–92 years) was used. Decellularization of human conjunctiva was achieved to 99% or greater DNA removal (p < 0.001) with absence of nuclear staining. This was reproducible at the lowest concentration of sodium dodecyl sulfate (0.05% w/v). No collagen denaturation (p = 0.74) and no difference in tensile strength parameters was demonstrated following decellularization. No significant difference was noted in the immunolocalization of collagen IV, laminin and fibronectin, or in the appearance of periodic acid–Schiff‐stained basement membranes following decellularization. The decellularized tissue did not exhibit any cytotoxicity and explant culture resulted in the growth of stratified conjunctival epithelium. Allogeneic decellularized human conjunctiva can be successfully decellularized using the described protocol. It represents a novel substrate to support the expansion of conjunctival epithelium for ocular surface cellular replacement therapies. Copyright © 2017 John Wiley & Sons, Ltd.     

Radio Frequency Ablation and Pulsed Radiofrequency for Treating Peripheral Neuralgias

Purpose of Review

Peripheral nerve pain is common among patients with typical management including the use of pain medications, neuropathic agents, steroid injections, and nerve blocks. Additionally, the use of pulsed radiofrequency (PRF) and radiofrequency ablation (RFA) can be used in the management of chronic peripheral nerve pain. Previous studies investigating the effectiveness of RFA and PRF, typically case reports, have demonstrated that peripheral nerve RFA and PRF have the potential to provide relief of chronic pain for long duration. Our study aimed at testing efficacy of RFA/PRF for treating peripheral neuralgia. This was a retrospective review. We identified 16 patients who received 17 RFAs/PRFs. Outcomes of interest collected included pain scores before and after procedures, percent improvement in pain after each procedure, and duration of improvement until the time of data collection. In addition, demographic data including age, sex, and nerves involved were collected.

Recent Findings

Eleven patients (12 RFAs/PRFs) (80%) reported improvement after their procedure. Pain scores improved significantly from 6.3?±?2.3 before each procedure to 3.6?±?2.7 after each procedure (p?=?0.003). Eleven patients (12 RFAs/PRFs) reported an average improvement of 60.8%?±?35% after their procedure with an average duration of improvement of 128.8?±?106.8 days.

Summary

RFA and PRF can be used to treat chronic peripheral pain after conservative methods fail to do so. Large clinical trials are needed to confirm our finding.

     

Amphotropic or Gibbon Ape Leukemia Virus Retrovirus Binding and Transduction Correlates with the Level of Receptor mRNA in Human Hematopoietic Cell Lines

ABSTRACT: The low level of amphotropic retrovirus mediated gene transfer into human hematopoietic stem cells (HSC) has been an impediment to gene therapy for hematopoietic diseases (1). We have previously shown that mouse and human HSC have low levels of the mRNA encoding PiT-2, the amphotropic retrovirus receptor. We hypothesized that the low level of PiT-2 mRNA was responsible for the low frequency of transduction of HSC by amphotropic retroviral vectors (2). In this study we compared the level of PiT-2 and PiT-1, the Gibbon Ape Leukemia Virus receptor (GaLV), in 5 human tissue culture cell lines. PiT-2 and PiT-1 mRNA levels were highest in K562 cells and lowest in HL60 cells. In hematopoietic cell lines, the level of PiT-2 or PiT-1 mRNA correlated directly with retrovirus binding and transduction with the appropriate (amphotropic or GaLV) retrovirus vector. The level of expression of PiT-2 and PiT-1 mRNA could be increased by treatment of HL60 cells with either PMA or Interleukin-1α. The increase in the level of PiT-2 and PiT-1 mRNA correlated with increased transduction with both amphotropic and GaLV retroviral vectors. We conclude that the improved transduction was a direct effect of the increased levels of receptor mRNA and unrelated to changes in the cell cycle status.     

Dementia assessment in primary care: results from a study in three managed care systems

BACKGROUND: Prior research has found that dementia is often undiagnosed in primary care, but there has been limited research on whether physicians respond to symptoms, behaviors, or other events that may be indicators of dementia. METHODS: A cross-sectional cohort study design was used to screen 553 patients aged 75 years or older for dementia in 3 managed health care systems in Portland, Oregon. For participants determined to be cognitively impaired, their medical charts were reviewed to determine if they had experienced adverse events, had been clinically evaluated for possible dementia, had received a diagnosis of dementia, or had been offered treatment. RESULTS: Nearly 43% of participants were identified as cognitively impaired: 29.7% were classified as mildly cognitively impaired (MI) and 13.7% as moderately to severely cognitively impaired (MSI). Eighteen percent of the MI group and 34.8% of the MSI group had evidence in their medical chart of having been clinically evaluated for dementia. None of the MI group and only 4.3% of the MSI group had been offered a cholinesterase inhibitor. Nearly two thirds (61.6%) of the MI and three fourths (75.4%) of the MSI participants had experienced 1 or more adverse events. Of those who had experienced adverse events, less than one quarter (23.7%) in the MI group and less than one half (44.2%) in the MSI group had received a clinical evaluation for dementia. CONCLUSIONS: These findings suggest the need for greater attention by primary care physicians to the cognitive functioning of older patients, especially patients who experience adverse events that may be indicators of dementia.