Prescribing issues experienced by people living with Phenylketonuria in the UK

Background: Foods for Special Medical purposes (Phe-free protein substitutes [PS] and low protein foods [LPFs]) are central to successful dietary management of patients with phenylketonuria (PKU). In the UK, PS and LPFs are prescribed by primary care general practitioners (GPs) and dispensed by high street pharmacists or via home delivery companies. As patients and carers commonly reported access issues with PS and LPFs through the National Society for PKU (NSPKU) helpline, the NSPKU collected more information about the extent of prescriptions issues via a questionnaire. Methods: A cross sectional online survey was carried out (consisting of 7 multiple choice and 3 open questions). The questionnaire was available via the NSPKU website over a nine-month period (15th May 2018 to 31st January 2019). Carers or patients with PKU were invited to participate if they had any problems accessing PS and LPF over a 9-month period. Results: There were 252 responses. 65% for children and 35% for adults, aged ≥18y with PKU. 59% (n=146/246) of responses described difficulties accessing basic LPF (bread, pasta) and 33% (n=81/248) PS. 36% (n=88/248) said problems had re-occurred during >1y, and 40% (n=99/248) for < 3 months. 59% (n= 146/246) had supply issues with LPF and 33% (n= 81/246) with PS. 18% (n=42/234) reported that the local NHS authority had refused, restricted or had a policy to block treatment access; 27% (n=63/234) cited GPs declining requests or restricting prescription amounts. 21% (n=49/234) could not access all their products via a pharmacy, 40% (n=93/234) said their home delivery system failed, and 15% (n=34/234) of the dispensed prescribed products were out of date, incorrect, damaged or poor quality. For patients and carers these issues caused: stress (87%, n=210/241); they considered PKU was not taken seriously by professionals (66%, n=160/241); they reduced patient access to LPF and PS (53%, n=128/241); and affected the patients’ health (53%, n=128/241)

Living with Phenylketonuria: lessons from the PKU community

Introduction: We report the practical, social and psychological issues of living with phenylketonuria (PKU) from one of the largest surveys that has been completed by both adults with PKU and parents/caregivers of children. Methods: In the UK, parents/caregivers of children and adults with PKU were invited to complete an online survey between November 2017 to January 2018 by the NSPKU (National Society for Phenylketonuria). Results: 631 participants (adults, n=338; parents/caregivers of children, n=293) with PKU completed the questionnaire. Problems experienced by children with PKU were: difficulty with maintaining focus (48%,n=114/236), educational difficulties (28%, n=67/236), anxiety or depression (29%, n=68/236), and gastrointestinal symptoms (34%, n=97/282). Fifty one per cent (n=120/236) described social exclusion; 17% (n=41/236) had relationship issues with friends or family. Problems experienced by adults were: depression or anxiety (52%, n=148/286), difficulty maintaining focus (54%, n=154/286), and low mood (54%, n=180/334). Difficulties were experienced with relationships (34%, n=96/286); social exclusion (44%, n=126/286); and gastrointestinal issues (n=34%, n=112/334). Common medications used included antidepressants (40%, n=131/331) and anxiolytics (18%, n=60/334). Discussions: Adults with PKU or caregivers/parents of children identified significant neurocognitive, mental health and general health issues. Limits on socialisation, perception of social isolation and dietary stigma are major obstacles which are difficult to overcome with conventional dietary management

Reproductive experience of women living with phenylketonuria

Introduction: Many women with PKU are well-informed about the risks of maternal PKU but there are several barriers to achieving satisfactory metabolic control before and during pregnancy. Many studies have documented the outcome of maternal PKU infants, but very little has been reported about the experiences of women of reproductive age with PKU, particularly about their psychosexual development, pre-conception, pregnancy and postnatal experience. Methods: In the UK, in a subsection of an online questionnaire conducted by the National Society for PKU (NSPKU) about living with PKU, women aged 18 years and over completed 9 closed questions about their pre-conception, pregnancy and post-natal experiences and an open-ended question on their reproductive health. Results: 300 women aged 18 years and over with PKU completed this questionnaire with 37% (n= 111/300) of women already having children. 56% (n= 71/128) of pregnancies were planned and a further 18% (n= 23/128) of women had both planned and unplanned pregnancies. Most women (73%, n=200/273) expressed concerns, fears and distress about pregnancy and two thirds of women who had at least one pregnancy stated that having PKU made pregnancy more stressful and difficult. 60% (n= 164/273) were concerned that they may cause harm to a baby, 58% (n= 159/273) worried about their ability to manage a strict diet during pregnancy, 54% (n= 147/273) had anxiety about their ability to maintain blood Phe within target range, and 48% (n= 132/273) feared having an unplanned pregnancy. Postnatally, 48% (n= 45/93) had low mood or sadness, 42% (n= 38/93) were depressed, 34% (n= 32/93) felt unable to cope, 33% (n= 31/93) said they could not manage their PKU and care for their baby, 14% (n= 13/93) struggled with child care needs and 4% (n= 4/94) worried they might hurt themselves or their baby through being unable to manage their diet. Conclusions: Many women with PKU have unmet sexual and reproductive health needs Pregnancy fears are prominent from adolescence onwards and for some women overarching concerns about their ability to cope with pregnancy led to a decision not to have children. Interventions are needed to reduce the psychological impact of the risk of maternal PKU syndrome and assist with safe pregnancies. Post-natal experiences of women with PKU give rise to concern

Preparation and biological investigation of luminescent water soluble CdTe nanoparticles

In this study CdTe quantum dots have been successfully prepared in aqueous medium using several different thiol stabilizers. The resulting nanocrystals were purified and the photoluminescence efficiency was subsequently enhanced through post preparative procedures such as photochemical etching and ageing. An optical study was carried out on the resulting CdTe nanocrystals as proof as their improvement. Preliminary tests of the thiol stabilised QDs as potential biolabels have been performed. It has been shown that L-cysteine stabilised QDs localising to the outer cell membrane in living cells. TGA stabilised CdTe QDs can potentially serve as live cell imaging tools as they exhibit strong luminescence and excellent photostability. In addition, the ability of TGA stabilised CdTe QDs to traverse the cell membrane of macrophages is a formidable quality that may potentially be harnessed for imaging and therapeutics. Modulating the delivery of QDs to subcellular locations in living cells opens a myriad of potential applications ranging from drug delivery to examination of intracellular processes

Aortic regurgitation in athletes: The challenges of echocardiographic interpretation

Background Bicuspid aortic valve (BAV) is the most common congenital cardiac defect and prone to premature degeneration causing aortic regurgitation (AR). The assessment of AR in athletic individuals poses several challenges as the pathological left ventricle (LV) remodelling caused by AR may overlap with the physiological remodelling of intense exercise. The purpose of this study is to highlight these challenges, review the existing literature and discuss how to tackle these conundrums. As a real-world example, we compare the resting transthoracic echocardiographic (TTE) findings in a cohort of individuals with BAV and AR, sub-grouped into “highly active” or “lightly active”. Methods Adult male subjects with an index TTE performed at a tertiary referral centre between 2019 and 2022 were included if the TTE confirmed a BAV and at least moderate AR. Further strict inclusion criteria were applied and parameters of valve disease severity was made in accordance with existing guidelines. Subjects completed a physical activity questionnaire over the telephone, and were classified into either group 1: “highly active” or group 2: “lightly active” based on their answers. Demographics and TTE parameters were compared between the two groups. Results 30 male subjects (mean age 44±13 years) with BAV-AR were included – 17 were highly active, and 13 lightly active. There was no significant difference in age (group 1, 45±12.7yrs vs group 2, 42±17yrs; p=0.49), height (p=0.45), weight (p=0.268) or severity of AR, when quantitative assessment was possible. Group 1 had a significantly higher stroke volume (131±17mls vs 102±13 mls; p=0.027), larger LV volumes, diastolic dimensions and significantly larger bi-atrial and right ventricular size. This LV dilatation in the context of AR and athleticism poses a diagnostic and management conundrum. Despite this, none of these 17 highly active individuals demonstrated any of the traditional criteria used to consider surgery. Conclusion There is significant overlap between the physiological adaptations to exercise and those caused by AR. Multi-modality imaging and stress testing can aid clinicians in diagnostic and management decisions in exercising individuals when there is discordance between AR severity and symptoms

Control-oriented modelling and simulation of a variable-frequency efficiency-optimized flyback converter

Driven by the requirement for a fairly accurate and fast simulation of a variable frequency digital controlled flyback converter, this paper develops a control-oriented mathematical model, which retains the essential dynamic characteristics of the real system, but offers significant computational complexity reduction compared to a full modelling approach. In addition to the model simplification, an approach to further improve the simulation speed, through a specific implementation of the differential equation solver, is also considered. To verify the accuracy of the proposed model, different tests with both open-loop and closed-loop flyback converters are performed. The results from both simulation and experiment show good agreement in all the test cases

The extent, variability, and attitudes towards volunteering among undergraduate nursing students: implications for pedagogy in nurse education

In the aftermath of the Francis Report nurses are being called to account for an apparent lack of care and compassion, leading to debate around pedagogy in nurse education. Absent from this debate is a consideration of student volunteering within undergraduate nursing programmes and its potential to promote student nurses self-esteem and to enhance the development of critical thinking skills. The aim of this study was therefore to understand the extent of and attitudes towards volunteering among nursing students. A mixed methods approach using a specifically developed questionnaire, followed by in-depth interviews to ascertain extent, variability, and attitudes towards volunteering revealed low levels of volunteering among nursing students. Limited time, limited access, and lack of academic support were cited as reasons. Nevertheless, students displayed positive attitudes towards volunteering. While volunteering has been shown to impact upon students abilities to think critically, to develop personal values and respond to the needs of others, volunteering within the UK undergraduate nursing programme considered is neither structured nor formalized. Nurse educators should pay attention to the positive benefits of volunteering for nursing students and consider ways in which volunteering might be incorporated into the curriculum

Convergent validity of ratings of perceived exertion during resistance exercise in healthy participants: A systematic review and meta-analysis

Background: The validity of ratings of perceived exertion (RPE) during aerobic training is well established; however, it’s validity during resistance exercise is less clear. This meta-analysis used the known relationships between RPE and exercise intensity (EI), heart rate (HR), blood lactate (BLa), blood pressure (BP) and electromyography (EMG) to determine the convergent validity of RPE as a measure of resistance exercise intensity and physiological exertion, during different forms of resistance exercise. Additionally, this study aims to assess the effect of several moderator variables on the strength of the validity coefficients, so that clearer guidance can be given on the use of RPE during resistance exercise. Methods: An online search of 4 databases and websites (PubMed, Web of science, SPORT Discus and Research Gate) was conducted up to 28 February 2020. Additionally, the reference lists of the included articles were inspected manually for further unidentified studies. The inclusion criteria were; healthy participants of any age, a rating scale used to measure RPE, resistance exercise of any type, one cohort receiving no other intervention, and must present data from one of the following outcome measures: EI, HR, BP, EMG or BLa. Weighted mean effect sizes (r) were calculated using a random-effects model. Heterogeneity was assessed using the Tau2 and I2 statistics. Moderator analysis was conducted using random-effects meta-regression. Results: One-hundred and eighteen studies were included in the qualitative synthesis, with 75 studies (99 unique cohorts) included in the meta-analysis. The overall weighted mean validity coefficient was large (0.88; 95% CI 0.84 to 0.91) and between studies heterogeneity was very large (Tau2 = 0.526, I2 = 96.1%). Studies using greater workload ranges, isometric muscle actions, and those that manipulated workload or repetition time, showed the highest validity coefficients. Conversely, sex, age, training status, RPE scale used, and outcome measure did not have an effect. Conclusions: RPE provides a valid measure of exercise intensity and physiological exertion during resistance exercise, with effect sizes comparable or greater than those shown during aerobic exercise. Therefore, RPE may provide an easily accessible means of prescribing and monitoring resistance exercise training. Registration: The systematic review protocol was registered on the PROSPERO database (CRD42018102640)

HOw patients view extended half‐life products: impressions from real‐world experience (The HOPE study)

Introduction Extended half‐life (EHL) clotting factors have been shown to offer people with haemophilia (PwH) protection from bleeding with fewer infusions, which might reduce treatment burden. Aim The HOw Patients view Extended half‐life products (HOPE) study aimed to explore, understand and describe patient expectations around the prophylactic use of EHL products and to establish whether these expectations were met through individual follow‐up analysis. Methods The HOPE study was a prospective, qualitative cohort study conducted among PwH who had switched to Fc fusion protein EHL products in routine clinical care and who had not been recruited to clinical trials of these products. Semi‐structured audio‐recorded interviews were undertaken over two time points; transcripts were analysed to systematically generate theory from data that contains both inductive and deductive thinking. Results Forty‐three interviews were conducted with 25 participants. Most participants were positive about EHL treatment and intended to continue using them. Reduced frequency of infusions meant lives were less disrupted or dominated by haemophilia, and there was less perceived stress on overused veins. For those PwH who did not reduce infusion frequency, there were other perceived benefits from EHLs with respect to greater protection with higher trough levels and fewer bleeds. Conclusion Patients switching to EHL treatments believe these products will result in fewer infusions and less disruption of everyday life, leaving them feeling more protected with fewer bleeds and increased activity levels, as well as enhanced well‐being and mental health. Understanding patient expectation and experience around using products adds real‐world data to clinical trial experience