Development of a core outcome set for clinical trials in childhood asthma: a survey of clinicians, parents, and young people

In clinical trials in childhood asthma, outcomes reflecting short-term disease activity are frequently measured, whilst functional status, quality of life (QoL), and long-term treatment effects are rarely assessed. There is also non-uniformity across studies in the selection and measurement of outcomes within these domains. The development of a core outcome set has the potential to reduce heterogeneity between trials, lead to research that is more likely to have measured relevant outcomes, and enhance the value of evidence synthesis by reducing the risk of outcome reporting bias and ensuring that all trials contribute usable information

Development and inter-rater reliability of the Liverpool adverse drug reaction causality assessment tool.

To develop and test a new adverse drug reaction (ADR) causality assessment tool (CAT)

A Novel Peptide Hydrogel for an Antimicrobial Bandage Contact Lens

A peptide hydrogel with an antimicrobial activity is developed as a bandage contact lens. The antimicrobial activity is enhanced with the addition of the biomolecules penicillin G or poly‐ε‐lysine and is positive against Staphylococcus aureus and Escherichia coli . The lens is also noncytotoxic toward a human corneal epithelial cell line and as a consequence is of great potential as a drug‐eluting bandage lens replacing conventional corneal ulcer treatment

Neuroimaging of tissue microstructure as a marker of neurodegeneration in the AT(N) framework: defining abnormal neurodegeneration and improving prediction of clinical status

Background: Alzheimer’s disease involves accumulating amyloid (A) and tau (T) pathology, and progressive neurodegeneration (N), leading to the development of the AD clinical syndrome. While several markers of N have been proposed, efforts to define normal vs. abnormal neurodegeneration based on neuroimaging have been limited. Sensitive markers that may account for or predict cognitive dysfunction for individuals in early disease stages are critical. Methods: Participants (n = 296) defined on A and T status and spanning the AD-clinical continuum underwent multi-shell diffusion-weighted magnetic resonance imaging to generate Neurite Orientation Dispersion and Density Imaging (NODDI) metrics, which were tested as markers of N. To better define N, we developed age- and sex-adjusted robust z-score values to quantify normal and AD-associated (abnormal) neurodegeneration in both cortical gray matter and subcortical white matter regions of interest. We used general logistic regression with receiver operating characteristic (ROC) and area under the curve (AUC) analysis to test whether NODDI metrics improved diagnostic accuracy compared to models that only relied on cerebrospinal fluid (CSF) A and T status (alone and in combination). Results: Using internal robust norms, we found that NODDI metrics correlate with worsening cognitive status and that NODDI captures early, AD neurodegenerative pathology in the gray matter of cognitively unimpaired, but A/T biomarker-positive, individuals. NODDI metrics utilized together with A and T status improved diagnostic prediction accuracy of AD clinical status, compared with models using CSF A and T status alone. Conclusion: Using a robust norms approach, we show that abnormal AD-related neurodegeneration can be detected among cognitively unimpaired individuals. Metrics derived from diffusion-weighted imaging are potential sensitive markers of N and could be considered for trial enrichment and as outcomes in clinical trials. However, given the small sample sizes, the exploratory nature of the work must be acknowledged

Patient-Specific Prosthetic Fingers by Remote Collaboration - A Case Study

The concealment of amputation through prosthesis usage can shield an amputee from social stigma and help improve the emotional healing process especially at the early stages of hand or finger loss. However, the traditional techniques in prosthesis fabrication defy this as the patients need numerous visits to the clinics for measurements, fitting and follow-ups. This paper presents a method for constructing a prosthetic finger through online collaboration with the designer. The main input from the amputee comes from the Computer Tomography (CT) data in the region of the affected and the non-affected fingers. These data are sent over the internet and the prosthesis is constructed using visualization, computer-aided design and manufacturing tools. The finished product is then shipped to the patient. A case study with a single patient having an amputated ring finger at the proximal interphalangeal joint shows that the proposed method has a potential to address the patient's psychosocial concerns and minimize the exposure of the finger loss to the public.Comment: Open Access articl

Characterization of Tunable Poly-ε-Lysine-Based Hydrogels for Corneal Tissue Engineering

A family of poly-ε-lysine hydrogels can be synthesized by crosslinking with bis-carboxylic acids using carbodiimide chemistry. In addition to creating hydrogels using a simple cast method, a fragmented method is used to introduce increased porosity within the hydrogel structure. Both methods have created tunable characteristics ranging in their mechanical properties, transparency, and water content, which is of interest to corneal tissue engineering and can be tailored to specific cellular needs and applications. With a worldwide shortage of cornea donor tissue available for transplant and limitations including rejection and potential infection, a synthetic material that can be used as a graft, or a partial thickness corneal replacement, would be an advantageous treatment method. These hydrogels can be tuned to have similar mechanical and transparency properties to the human cornea. They also support the attachment and growth of corneal epithelial cells and the integration of corneal stromal cells

Effective Feedback to Improve Primary Care Prescribing Safety (EFIPPS) a pragmatic three-arm cluster randomised trial:designing the intervention (ClinicalTrials.gov registration NCT01602705)

Peer reviewedPublisher PD

In Males with Adequate Dietary Needs Who Present No Sleep Disturbances, Is an Acute Intake of Zinc Magnesium Aspartate, Following Either Two Consecutive Nights of 8 or 4 h of Sleep Deprivation, Beneficial for Sleep and Morning Stroop Interference Performance?

PURPOSE: Purpose: We examined whether supplementation of zinc magnesium aspartate (ZMA) in two groups of males, either partially sleep-restricted (4 h) or with habitual sleep (8 h) for 2 nights, was beneficial for sleep and subsequent morning Stroop performance. METHODS: Participants were randomly allocated to two independent groups who either had 4 h (33 males) or 8 h (36 males) sleep for two nights. Using a double-blinded, randomised counterbalanced design, they then completed five sessions, (i) two familiarisation sessions including 7 days of sleep and dietary intake, (ii) three conditions with 4 h or 8 h sleep and either NoPill control (NoPill), placebo (PLAC) or ZMA (ZMA). Sleep was assessed by actimetry and sleep questionnaires, and cognitive performance was assessed by the Stroop test. The data were analysed using a general linear model with repeated measures. RESULTS: A main effect for "sleep" (4 or 8 h) was found, where more opportunity to sleep resulted in better "sleep" metrics (both objective and subjective) as well as better Stroop scores (lower colour-interference and word-interference scores and lower error in words). No main effect for "Pill" was found other than the mood state depression, where subjective ratings for the PLAC group were lower than the other two conditions. Interactions were found in anger, ease to sleep and waking time. CONCLUSION: Having 8 h opportunity to sleep resulted in better "sleep" metrics as well as better Stroop scores compared to 4 h. Supplementation of ZMA for 4 or 8 h for 2 nights had no effect on subsequent morning cognitive performance but reduced sleep or total sleep time by ~0.46 h compared to the other conditions. An interaction was found where sleep time was reduced by ~0.94 h in the ZMA group in the 8 h condition compared to NoPill or PLAC

Inappropriate prescribing and adverse drug events in older people

Inappropriate prescribing (IP) in older patients is highly prevalent and is associated with an increased risk of adverse drug events (ADEs), morbidity, mortality and healthcare utilisation. Consequently, IP is a major safety concern and with changing population demographics, it is likely to become even more prevalent in the future. IP can be detected using explicit or implicit prescribing indicators. Theoretically, the routine clinical application of these IP criteria could represent an inexpensive and time efficient method to optimise prescribing practice. However, IP criteria must be sensitive, specific, have good inter-rater reliability and incorporate those medications most commonly associated with ADEs in older people. To be clinically relevant, use of prescribing appropriateness tools must translate into positive patient outcomes, such as reduced rates of ADEs. To accurately measure these outcomes, a reliable method of assessing the relationship between the administration of a drug and an adverse clinical event is required. The Naranjo criteria are the most widely used tool for assessing ADE causality, however, they are often difficult to interpret in the context of older patients. ADE causality criteria that allow for the multiple co-morbidities and prescribed medications in older people are required. Ultimately, the current high prevalence of IP and ADEs is unacceptable. IP screening criteria need to be tested as an intervention to assess their impact on the incidence of ADEs in vulnerable older patients. There is a role for IP screening tools in everyday clinical practice. These should enhance, not replace good clinical judgement, which in turn should be based on sound pharmacogeriatric training

Effects of an Acute Dose of Zinc Monomethionine Asparate and Magnesium Asparate (ZMA) on Subsequent Sleep and Next-Day Morning Performance (Countermovement Jumps, Repeated Sprints and Stroop Test)

The goal of the present study was to determine whether an acute dose of a zinc-containing nutritional supplement (ZMA) has any effects on sleep and morning performance in recreationally trained males. Nineteen males participated in a repeated-measures within-subjects study to assess objective and subjective measures of sleep, completed counter-movement jumps (CMJ) and repeated sprint morning performance (RSP). Three days of baseline food intake showed no major deficiencies of zinc, magnesium or vitamin B6 for all participants (11.9 ± 3.4, 395 ± 103 and 2.7 ± 0.9 mg.day−1, respectively). Sleep (22:30–06:30 h) was assessed via actimetry, and either a control (no tablets, NoPill), dextrose placebo (PLAC) or ZMA was ingested 30–60 min before retiring to bed for two nights. The participants undertook the three conditions (NoPill, PLAC or ZMA) administered in a counterbalanced order. The data were analyzed using general linear models with repeated measures. In healthy active males who consume diets of adequate micronutrients, sleep normally and maintain good sleep hygiene (time to bed and wake times), ZMA supplementation had no beneficial effect on RSP or performance in the Stroop test (p > 0.05) but did improve CMJ height (p 0.05). Supplementation of ZMA for two nights had no effect on sleep, RSP or cognitive function. The NoPill condition elucidated the effects of the intervention under investigation