e-Consent in UK academic-led clinical trials: current practice, challenges and the need for more evidence

BACKGROUND: During the COVID-19 pandemic, in-person healthcare visits were reduced. Consequently, trial teams needed to consider implementing remote methods for conducting clinical trials, including e-Consent. Although some clinical trials may have implemented e-Consent prior to the pandemic, anecdotes of uptake for this method increased within academic-led trials. When the increased use of this process emerged, representatives from several large academic clinical trial groups within the UK collaborated to discuss ways in which trialists can learn from one another when implementing e-Consent. METHODS: A survey of UKCRC-registered Clinical Trials Units (CTUs) was undertaken in April–June 2021 to understand the implementation of and their views on the use of e-Consent and experiences from the perspectives of systems programmers and quality assurance staff on the use of e-Consent. CTUs not using e-Consent were asked to provide any reasons/barriers (including no suitable trials) and any plans for implementing it in the future. Two events for trialists and patient and public involvement (PPI) representatives were then held to disseminate findings, foster discussion, share experiences and aid in the identification of areas that the academic CTU community felt required more research. RESULTS: Thirty-four (64%) of 53 CTUs responded to the survey, with good geographical representation across the UK. Twenty-one (62%) of the responding CTUs had implemented e-Consent in at least one of their trials, across different types of trials, including CTIMPs (Clinical Trial of Investigational Medicinal Product), ATIMPs (Advanced Therapy Medicinal Products) and non-CTIMPs. One hundred ninety-seven participants attended the two workshops for wide-ranging discussions. CONCLUSION: e-Consent is increasingly used in academic-led trials, yet uncertainties remain amongst trialists, patients and members of the public. Uncertainties include a lack of formal, practical guidance and a lack of evidence to demonstrate optimal or appropriate methods to use. We strongly encourage trialists to continue to share their own experiences of the implementation of e-Consent

Assessing copper fertility of intrusive rocks using field portable X-Ray fluorescence (pXRF) data

Based on a global compilation of whole-rock geochemical data, Sr/Y and Sr/MnO are identified as effective discriminators between ore-forming and unprospective intrusions in the porphyry Cu setting. Intrusive rocks are classified into three fertility groups prospective, unprospective and mixed-signal designed to assist explorers as a discrimination tool, narrowing the exploration search space in porphyry Cu districts.Portable X-ray fluorescence (pXRF) data of Sr, Y and MnO were collected on pulp powders and rock slabs from six porphyry Cu (±Mo ± Au) districts. Pre- and post-mineralization intrusions from porphyry Cu districts have lower Sr/Y and Sr/MnO values than syn-mineralization intrusions from the same districts, although absolute values are variable between districts.pXRF data were compared to conventional whole-rock data to determine if pXRF data were appropriate substitutes for conventional whole-rock methods of evaluating the ore-forming potential of intrusive rocks. pXRF data collected on pulp material were found to be more accurate (within 16% of conventional methods) and more precise

A systematic review of the safety of lisdexamfetamine dimesylate

BACKGROUND: Here we review the safety and tolerability profile of lisdexamfetamine dimesylate (LDX), the first long-acting prodrug stimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD). METHODS: A PubMed search was conducted for English-language articles published up to 16 September 2013 using the following search terms: (lisdexamfetamine OR lisdexamphetamine OR SPD489 OR Vyvanse OR Venvanse OR NRP104 NOT review [publication type]). RESULTS: In short-term, parallel-group, placebo-controlled, phase III trials, treatment-emergent adverse events (TEAEs) in children, adolescents, and adults receiving LDX were typical for those reported for stimulants in general. Decreased appetite was reported by 25-39 % of patients and insomnia by 11-19 %. The most frequently reported TEAEs in long-term studies were similar to those reported in the short-term trials. Most TEAEs were mild or moderate in severity. Literature relating to four specific safety concerns associated with stimulant medications was evaluated in detail in patients receiving LDX. Gains in weight, height, and body mass index were smaller in children and adolescents receiving LDX than in placebo controls or untreated norms. Insomnia was a frequently reported TEAE in patients with ADHD of all ages receiving LDX, although the available data indicated no overall worsening of sleep quality in adults. Post-marketing survey data suggest that the rate of non-medical use of LDX was lower than that for short-acting stimulants and lower than or equivalent to long-acting stimulant formulations. Small mean increases were seen in blood pressure and pulse rate in patients receiving LDX. CONCLUSIONS: The safety and tolerability profile of LDX in individuals with ADHD is similar to that of other stimulants

A systems approach to prion disease

Prions cause transmissible neurodegenerative diseases and replicate by conformational conversion of normal benign forms of prion protein (PrPC) to disease-causing PrPSc isoforms. A systems approach to disease postulates that disease arises from perturbation of biological networks in the relevant organ. We tracked global gene expression in the brains of eight distinct mouse strain–prion strain combinations throughout the progression of the disease to capture the effects of prion strain, host genetics, and PrP concentration on disease incubation time. Subtractive analyses exploiting various aspects of prion biology and infection identified a core of 333 differentially expressed genes (DEGs) that appeared central to prion disease. DEGs were mapped into functional pathways and networks reflecting defined neuropathological events and PrPSc replication and accumulation, enabling the identification of novel modules and modules that may be involved in genetic effects on incubation time and in prion strain specificity. Our systems analysis provides a comprehensive basis for developing models for prion replication and disease, and suggests some possible therapeutic approaches

Asymptomatic bacteriuria in sickle cell disease: a cross-sectional study

BACKGROUND: It is known that there is significant morbidity associated with urinary tract infection and with renal dysfunction in sickle cell disease (SCD). However, it is not known if there are potential adverse outcomes associated with asymptomatic bacteriuria (ASB) infections in sickle cell disease if left untreated. This study was undertaken to determine the prevalence of ASB, in a cohort of patients with SCD. METHODS: This is a cross-sectional study of patients in the Jamaican Sickle Cell Cohort. Aseptically collected mid-stream urine (MSU) samples were obtained from 266 patients for urinalysis, culture and sensitivity analysis. Proteinuria was measured by urine dipsticks. Individuals with abnormal urine culture results had repeat urine culture. Serum creatinine was measured and steady state haematology and uric acid concentrations were obtained from clinical records. This was completed at a primary care health clinic dedicated to sickle cell diseases in Kingston, Jamaica. There were 133 males and 133 females in the sample studied. The mean age (mean ± sd) of participants was 26.6 ± 2.5 years. The main outcome measures were the culture of ≥ 10(5 )colony forming units of a urinary tract pathogen per milliliter of urine from a MSU specimen on a single occasion (probable ASB) or on consecutive occasions (confirmed ASB). RESULTS: Of the 266 urines collected, 234 were sterile and 29 had significant bacteriuria yielding a prevalence of probable ASB of 10.9% (29/266). Fourteen patients had confirmed ASB (prevalence 5.3%) of which 13 had pyuria. Controlling for genotype, females were 14.7 times more likely to have confirmed ASB compared to males (95%CI 1.8 to 121.0). The number of recorded visits for symptomatic UTI was increased by a factor of 2.5 (95% CI 1.4 to 4.5, p < 0.005) but serum creatinine, uric acid and haematology values were not different in patients with confirmed ASB compared with those with sterile urine. There was no association with history of gram negative sepsis. CONCLUSION: ASB is a significant problem in individuals with SCD and may be the source of pathogens in UTI. However, further research is needed to determine the clinical significance of ASB in SCD