Pharmacokinetics of Envarsus in pediatric kidney transplant recipients - phase 1 pilot conversion study.

INTRODUCTION: Tacrolimus is the standard immunosuppressant for pediatric kidney transplants and is routinely administered twice daily (BD-tac). Envarsus (LCP-tac), an extended-release formulation, is approved for adults but not for pediatric patients. METHODS: We conducted a pilot open-label phase 1 study in stable pediatric kidney transplant recipients (age < 18 at the time of study). Our primary objective was to compare the pharmacokinetics (Pk) of LCP-tac versus BD-tac. We conducted two 24-h Pk studies: pre-conversion (BD-tac) and 4 weeks post-conversion to LCP-tac. Patients were followed for 6 months, with the option to continue LCP-tac. RESULTS: Five patients completed the study, with no returns to BD-tac. Median age was 15 years (range 11-17). LCP-tac exhibited an extended-release profile versus the bimodal profile of BD-tac. Time to maximum concentration was delayed (5 h vs. 1 h), and maximum concentration was lower (9.9 ng/mL vs. 14.4 ng/mL). Tacrolimus area under the curve (24 h) was comparable (141 ± 46.5 ng/mL vs. 164 ± 27.8 ng/mL). No new safety concerns arose. There were no rejection and no difference in eGFR at the study's end (1.5 mL/min/1.73 m2 , range - 1.7 to 2.3 mL/min/1.73 m2 ). Concentration/dose ratio was higher in LCP-tac (1.8 ± 0.64 vs. 0.8 ± 0.39). The final conversion ratio was 0.6 (BD-tac: LCP-tac). CONCLUSION: Our pilot study confirms the extended-release Pk profile and improved absorption of LCP-tac compared to BD-tac. A larger study is needed to further evaluate the population Pk characteristics in children.

Increasing SARS-CoV-2 seroprevalence among UK pediatric patients on dialysis and kidney transplantation between January 2020 and August 2021.

BACKGROUND: Coronavirus disease 2019 (COVID-19) was officially declared a pandemic by the World Health Organisation (WHO) on 11 March 2020, as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly across the world. We investigated the seroprevalence of anti-SARS-CoV-2 antibodies in pediatric patients on dialysis or kidney transplantation in the UK. METHODS: Excess sera samples were obtained prospectively during outpatient visits or haemodialysis sessions and analysed using a custom immunoassay calibrated with population age-matched healthy controls. Two large pediatric centres contributed samples. RESULTS: In total, 520 sera from 145 patients (16 peritoneal dialysis, 16 haemodialysis, 113 transplantation) were analysed cross-sectionally from January 2020 until August 2021. No anti-SARS-CoV-2 antibody positive samples were detected in 2020 when lockdown and enhanced social distancing measures were enacted. Thereafter, the proportion of positive samples increased from 5% (January 2021) to 32% (August 2021) following the emergence of the Alpha variant. Taking all patients, 32/145 (22%) were seropositive, including 8/32 (25%) with prior laboratory-confirmed SARS-CoV-2 infection and 12/32 (38%) post-vaccination (one of whom was also infected after vaccination). The remaining 13 (41%) seropositive patients had no known stimulus, representing subclinical cases. Antibody binding signals were comparable across patient ages and dialysis versus transplantation and highest against full-length spike protein versus spike subunit-1 and nucleocapsid protein. CONCLUSIONS: Anti-SARS-CoV-2 seroprevalence was low in 2020 and increased in early 2021. Serological surveillance complements nucleic acid detection and antigen testing to build a greater picture of the epidemiology of COVID-19 and is therefore important to guide public health responses. A higher resolution version of the Graphical abstract is available as Supplementary information.

The Evolution of Scientific Visualisations: A Case Study Approach to Big Data for Varied Audiences.

Visual representations of complex data are a cornerstone of how scientific information is shared. By taking large quantities of data and creating accessible visualisations that show relationships, patterns, outliers, and conclusions, important research can be communicated effectively to any audience. The nature of animal cognition is heavily debated with no consensus on what constitutes animal intelligence. Over the last half-century, the methods used to define intelligence have evolved to incorporate larger datasets and more complex theories-moving from relatively simple comparisons of brain mass and body mass to explorations of brain composition and how neuron count changes between specific groups of animals. The primary aim of this chapter is therefore to explore how visualisation choice influences the accessibility of complex scientific information, using animal cognition as a case study. As the datasets concerned with animal intelligence have increased in both size and complexity, have the visualisations that accompany them evolved as well? We first investigate how the basic presentation of visualisations (figure legends, inclusion of statistics, use of colour, etc.) has changed, before discussing alternative approaches that might improve communication with both scientific and general audiences. By building upon the types of visualisation techniques that everyone is taught at school (bar charts, XY scatter plots, pie charts, etc.), we show how small changes can improve our communication with both scientific and general audiences. We suggest that there is no single right way to visualise data, but careful consideration of the audience and the specific message can help, even where communications are constrained by time, technology, or medium.

Spoken propositional idea density, a measure to help second language English speaking students: A multicentre cohort study.

PURPOSE: Idea density has been shown to influence comprehension time for text in various populations. This study aims to explore the influence of spoken idea density on attainment in young, healthy subjects using demographic characteristics. METHODS: Students watched two online lectures and answered 10 multiple choice questions on them. Students received one more idea dense (MID) and one less idea dense (LID) lecture on two different subjects. RESULTS: Seventy-five students completed the study achieving a higher median score after a less idea-dense lecture (LID = 7(3), MID = 6(3), p = 0.04). Artificial neural network models revealed the first language as the main predictor of exam performance. The odds ratio (OR) of obtaining ≥70% after a more idea-dense lecture was six-time higher for the first language versus second language English speakers (OR = 5.963, 95% CI 1.080-32.911, p = 0.041). The odds ratio was not significant when receiving a less dense lecture (OR = 2.298, 95% CI 0.635-8.315, p = 0.205). Second-language speakers benefited from receiving a lower idea density, achieving a 10.8% score increase from high to low density, versus a 3.2% increase obtained by first language speakers. CONCLUSIONS: The propositional idea density of lectures directly influences students' comprehension, and disproportionately for second language speakers; revealing the possibility of reduced spoken idea density in levelling the attainment differential between first and second language speakers.

Dual pH-Responsive Macrophage-Targeted Isoniazid Glycoparticles for Intracellular Tuberculosis Therapy.

Tuberculosis (TB) is a global epidemic that kills over a million people every year, particularly in low-resource communities. Mycobacterium tuberculosis, the most common bacterium that causes TB, is difficult to treat, particularly in its latent phase, in part due to its ability to survive and replicate within the host macrophage. New therapeutic approaches resulting in better tolerated and shorter antibiotic courses that target intracellular bacteria are critical to effective treatment. The development of a novel, pH-responsive, mannosylated nanoparticle, covalently linked with isoniazid, a first-line TB antibiotic, is presented. This nanoparticle drug delivery agent has increased macrophage uptake and, upon exposure to the acidic phagolysosome, releases isoniazid through hydrolysis of a hydrazone bond, and disintegrates into a linear polymer. Full antibiotic activity is shown to be retained, with mannosylated isoniazid particles being the only treatment exhibiting complete bacterial eradication of intracellular bacteria, compared to an equivalent PEGylated system and free isoniazid. Such a system, able to effectively kill intracellular mycobacteria, holds promise for improved outcomes in TB infection.

Hydrogel and Organogel Formation by Hierarchical Self-Assembly of Cyclic Peptides Nanotubes.

Breaking away from the linear structure of previously reported peptide-based gelators, this study reports the first example of gel formation based on the use of cyclic peptides made of alternating d- and l-amino acids, known to self-assemble in solution to form long nanotubes. Herein, a library of cyclic peptides was systemically studied for their gelation properties in various solvents, uncovering key parameters driving both organogel and hydrogel formation. The hierarchical nature of the self-assembly process in water was characterised by a combination of electron microscopy imaging and small-angle X-ray scattering, revealing a porous network of entangled nanofibres composed by the aggregation of several cyclic peptide nanotubes. Rheology measurements then confirmed the formation of soft hydrogels.

Synthesis of Sub-100 nm Glycosylated Nanoparticles via a One Step, Free Radical, and Surfactant Free Emulsion Polymerization.

The facile synthesis of sub-100 nm glyco nanoparticles is presented via a one-step, free radical, and surfactant free emulsion polymerization. It is shown that by using sterically large, hydrophilic glycomonomers such as a lactose acrylamide with the charged azo initiator 4,4'-azobis(4-cyanovaleric acid), growing particles are stabilized enough to reproducibly produce well defined (PDi ≤ 0.1) glycoparticles with diameters below 100 nm.

Renal failure from birth-AKI or CKD? Questions.

A case is presented of a neonate born at 32 weeks of gestation with intra-uterine growth retardation. The renal scan performed at 31 weeks showed oligohydramnios but normal kidneys. The neonate was oliguric from birth and required early peritoneal dialysis. Her urine showed heavy proteinuria, and the plasma albumin was very low. Post-natal ultrasonography showed large bright kidneys with reduced corticomedullary differentiation but no dysplastia; arterial and venous flow was normal on Doppler ultrasound. The quiz discusses the differential diagnosis with particular reference to whether this picture represents acute kidney injury with expected improvement or chronic kidney disease. Further questions discuss mechanisms of renal failure in this situation. Finally, with reference to previous case reports and series, a correlation between a specific mutation and this severe phenotype is proposed.

Montelukast: a novel therapeutic option in eosinophilic peritonitis.

BACKGROUND: Eosinophilic peritonitis is a recognised complication of peritoneal dialysis and has an incompletely understood pathophysiology. Current treatment options, including change of dialysate, change of peritoneal dialysis modality, steroids or antihistamines, are supported only by case reports with a lack of controlled trials or evidence-based guidelines. Leukotrienes are proinflammatory arachidonic acid metabolites produced by leucocytes and are involved in eosinophil chemotaxis. Montelukast is an orally administered leukotriene receptor antagonist commonly used in managing childhood atopic illnesses and theoretically safe for use in patients with renal failure. CASE DIAGNOSIS AND TREATMENT: We describe the first reported case of recurrent, symptomatic, eosinophilic peritonitis in a 15-year-old girl successfully treated with leukotriene receptor antagonist montelukast after changes in dialysate and treatment with antihistamines failed to adequately control eosinophilic peritoneal infiltrates or symptoms. CONCLUSIONS: Current scientific understanding of leukotrienes and eosinophil migration suggest that montelukast may be a well-tolerated, safe and efficacious treatment for eosinophilic peritonitis complicating peritoneal dialysis. Further cases and comparative studies are required to develop an evidence base for treatment of this condition.

Decline in Left Ventricular Early Systolic Function with Worsening Kidney Function in Children with Chronic Kidney Disease: Insights from the 4C and HOT-KID Studies.

INTRODUCTION: Adults with childhood-onset chronic kidney disease (CKD) have an increased risk of cardiovascular disease. First-phase ejection fraction (EF1), a novel measure of early systolic function, may be a more sensitive marker of left ventricular dysfunction than other markers in children with CKD. OBJECTIVE: To examine whether EF1 is reduced in children with CKD. METHODS: Children from the 4C and HOT-KID studies were stratified according to estimated glomerular filtration rate (eGFR). The EF1 was calculated from the fraction of left ventricular (LV) volume ejected up to the time of peak aortic flow velocity. RESULTS: The EF1 was measured in children ages 10.9 ± 3.7 (mean ± SD) years, 312 with CKD and 63 healthy controls. The EF1 was lower, while overall ejection fraction was similar, in those with CKD compared with controls and decreased across stages of CKD (29.3% ± 3.7%, 23.5% ± 4.5%, 19.8% ± 4.0%, 18.5% ± 5.1%, and 16.7% ± 6.6% in controls, CKD 1, 2, 3, and ≥ 4, respectively, P < .001). The relationship of EF1 to eGFR persisted after adjustment for relevant confounders (P < .001). The effect size for association of measures of LV structure or function with eGFR (SD change per unit change in eGFR) was greater for EF1 (ß = 0.365, P < .001) than for other measures: LV mass index (ß = -0.311), relative wall thickness (ß = -0.223), E/e' (ß = -0.147), and e' (ß = 0.141) after adjustment for confounders in children with CKD. CONCLUSIONS: Children with CKD exhibit a marked and progressive decline in EF1 with falling eGFR. This suggests that EF1 is a more sensitive marker of LV dysfunction when compared to other structural or functional measures and that early LV systolic function is a key feature in the pathophysiology of cardiac dysfunction in CKD.

KidzMed e-learning to upskill student pharmacists to teach pill swallowing to children.

BACKGROUND: Appropriate medication use is essential in ensuring optimal pharmacotherapeutic outcomes. It is mistakenly assumed that adults can swallow solid oral dosage forms (SODFs, e.g. tablets/capsules colloquially referred to as 'pills'), without difficulty and that children cannot. KidzMed is a 'pill swallowing' training programme designed to teach effective SODF use in patients of all ages. It may be utilised by healthcare professionals to assist patients taking SODFs. E-learning was essential for training during COVID pandemic to reduce viral transmission. The aim of this study was to explore UK student pharmacists views of e-learning to support swallowing solid oral dosage forms. METHODS: This study used pre- and post-intervention online surveys on Microsoft Forms to evaluate self-directed eLearning about pill swallowing on MPharm programmes at three UK Universities using a 13-item survey. A combination of five-point Likert Scales and free-text items were used. The eLearning was available via the virtual learning environment at the University and embedded within existing curriculum. Descriptive statistical analysis was used to explore responses. RESULTS: In total, 113 of 340 (33%) students completed the survey. Seventy-eight percent (n = 65) reported the eLearning would enable them to teach adults and children to swallow SODFs successfully. Learners either agreed or strongly agreed that they felt comfortable to teach patients (95%, n = 62/113) and parents or carers (94%, n = 60) to swallow medications having completed the e-learning. Student pharmacists generally found eLearning as an acceptable way to reflect on their own experiences of 'pill' swallowing and how to support patients to swallow SODFs. CONCLUSION: The KidzMed eLearning was well received by student pharmacists. Further work is needed to explore whether skills translates into real life application in the clinical settings.

Intensive compared with less intensive blood pressure control to prevent adverse cardiac remodelling in children with chronic kidney disease (HOT-KID): a parallel-group, open-label, multicentre, randomised, controlled trial.

BACKGROUND: Optimal target blood pressure to reduce adverse cardiac remodelling in children with chronic kidney disease is uncertain. We hypothesised that lower blood pressure would reduce adverse cardiac remodelling. METHODS: HOT-KID, a parallel-group, open-label, multicentre, randomised, controlled trial, was done in 14 clinical centres across England and Scotland. We included children aged 2-15 years with stage 1-4 chronic kidney disease-ie, an estimated glomerular filtration rate (eGFR) higher than 15 mL/min per 1·73 m2-and who could be followed up for 2 years. Children on antihypertensive medication were eligible as long as it could be changed to angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) if they were not already receiving these therapies. Participants were randomly assigned (1:1) to standard treatment (auscultatory office systolic blood pressure target between the 50th and 75th percentiles) or intensive treatment (systolic target <40th percentile) by the chief investigator using a rapid, secure, web-based randomisation system. ACE inhibitors or ARBs were used as first-line agents, with the dose titrated every 2-4 weeks to achieve the target blood pressure levels. The primary outcome was mean annual difference in left ventricular mass index (LVMI) by echocardiography measured by a masked observer and was assessed in the intention-to-treat population, defined as all the children who underwent randomisation irrespective of the blood pressure reached. Secondary and safety outcomes were the differences between groups in mean left ventricular relative wall thickness, renal function, and adverse effects and were also assessed in the intention-to-treat population. This trial is registered with ISRCTN, ISRCTN25006406. FINDINGS: Between Oct 30, 2012, and Jan 5, 2017, 64 participants were randomly assigned to the intensive treatment group and 60 to the standard treatment group (median age of participants was 10·0 years [IQR 6·8-12·6], 69 [56%] were male and 107 [86%] were of white ethnicity). Median follow-up was 38·7 months (IQR 28·1-52·2). Blood pressure was lower in the intensive treatment group compared with standard treatment group (mean systolic pressure lower by 4 mm Hg, p=0·0012) but in both groups was close to the 50th percentile. The mean annual reduction in LVMI was similar for intensive and standard treatments (-1·9 g/m2·7 [95% CI -2·4 to -1·3] vs -1·2 g/m2·7 [-1·5 to 0·8], with a treatment effect of -0·7 g/m2·7 [95% CI -1·9 to 2·6] per year; p=0·76) and mean value in both groups at the end of follow-up within the normal range. At baseline, elevated relative wall thickness was more marked than increased LVMI and a reduction in relative wall thickness was greater for the intensive treatment group than for the standard treatment group (-0·010 [95% CI 0·015 to -0·006] vs -0·004 [-0·008 to 0·001], treatment effect -0·020 [95% CI -0·039 to -0·009] per year, p=0·0019). Six (5%) participants reached end-stage kidney disease (ie, an eGFR of <15 mL/min per 1·73 m2; three in each group) during the course of the study. The risk difference between treatment groups was 0·02 (95% CI -0·15 to 0·19, p=0·82) for overall adverse events and 0·07 (-0·05 to 0·19, p=0·25) for serious adverse events. Intensive treatment was not associated with worse renal outcomes or greater adverse effects than standard treatment. INTERPRETATION: These results suggest that cardiac remodelling in children with chronic kidney disease is related to blood pressure control and that a target office systolic blood pressure at the 50th percentile is close to the optimal target for preventing increased left ventricular mass. FUNDING: British Heart Foundation.

Advanced chronic kidney disease among UK children.

The UK Renal Registry currently collects information on UK children with kidney failure requiring long-term kidney replacement therapy (KRT), which supports disease surveillance and auditing of care and outcomes; however, data are limited on children with chronic kidney disease (CKD) not on KRT. METHODS: In March 2020, all UK Paediatric Nephrology centres submitted data on children aged <16 years with severely reduced kidney function as of December 2019, defined as an estimated glomerular filtration rate <30 mL/min/1.73 m2. RESULTS: In total, 1031 children had severe CKD, the majority of whom (80.7%) were on KRT. The overall prevalence was 81.2 (95% CI 76.3 to 86.3) per million of the age-related population. CONCLUSIONS: The prevalence of severe CKD among UK children is largely due to a high proportion of children on long-term KRT. Expanding data capture to include children with CKD before reaching failure will provide greater understanding of the CKD burden in childhood.

Pedagogic Interest Group: a novel and proven collaborative, adhocracy research group structure.

This article was migrated. The article was marked as recommended. Background: Teaching is a core activity for universities, and pedagogic research is essential for improving student experience, staff satisfaction, and research and teaching quality. Pedagogic research is often performed as a secondary research area or by part-time staff, requiring good collaboration. Existing research structures in universities often result in pedagogic research falling through the gaps and for quality work and pedagogic improvements to be missed. Aim: The aim was to develop a clear and flexible structure to improve participation and output of pedagogic research in the School of Pharmacy and Biomedical Sciences at the University of Central Lancashire. Method: A collaborative adhocracy called the Pedagogic Interest Group (PIG) was created in January 2020. It was designed to allow collaborative, flexible research projects to be easily set up by any staff member. The group supervises and organises a bespoke team of people for each project, drawing on all previously involved staff's expertise and contacts through an initial project meeting organised by an independent group chair. Each project group runs independently, with further help available from the group chairs. Results: Under the PIG structure, seven projects have been undertaken in less than one year. Two papers were published, one under review, two in preparation, one abstract accepted at an international conference, and fifteen funded undergraduate research projects completed. Part-time teaching staff are more involved in the research. Internally, three departments and externally, three other UK universities have been collaboratively involved in research projects. Conclusion: The PIG structure works and depends on staff's continued engagement and at least two independent chairs for impartiality and transparency.

Evaluation of students' performance and engagement using post-laboratory integrated assessments within a pharmacy course in the United Kingdom: a pilot cohort cross-over study.

INTRODUCTION: This pilot study investigated the impact of practice integrated, post-laboratory assessment on the scientific education and attitudes of first-year pharmacy students. Median assessment performance, achievement of full marks, and engagement in laboratory classes were evaluated. METHODS: The pilot randomised cross-over study was conducted at the University of Central Lancashire. Students were randomly assigned to two groups, and after undertaking four identical pharmaceutics laboratory classes, answered two science-based questions that were either integrated with practice using a contextualizing scenario or had no integration. Student performance and engagement were subsequently analysed. RESULTS: Thirty students completed the study. Students performed better in the integrated assessment (median 3.5; interquartile range [IQR] 2.00-4.00) compared to the non-integrated assessment (median 2; IQR 1.75-3.00) (P < .001). Twenty-five students (83%) achieved full marks with the integrated assessment (P = .006). Correlation (R2) for the integrated assessment was 0.90 and for the non-integrated assessment was 0.12. Engagement was positive in both groups but significantly improved in the domains of "instructor contribution" and "value of activity" (P = .01) when receiving the integrated assessment. CONCLUSIONS: Integrated and contextualized assessment of science teaching as a lone intervention increased pharmacy students' performance and engagement in laboratory classes without requiring any change to the teaching session itself.

Patient as teacher sessions contextualize learning, enhancing knowledge, communication, and participation of pharmacy students in the United Kingdom.

PURPOSE: This study aimed to evaluate the impact of Patient As Teacher (PAT) sessions on the knowledge, communication skills, and participation of pharmacy students in the United Kingdom. METHODS: During the academic year 2019-2020, year 1 and 2 pharmacy students at the University of Central Lancashire were invited to complete a questionnaire following PAT sessions. Data were analyzed by means of descriptive statistics, including mean and standard deviation (SD) for: continuous variables and reliability analysis. Pearson's Chi-Square or Fisher Exact Test, odds ratio, and Phi were used for analyzing dichotomous variables. Thematic analysis was used for free text comments. RESULTS: Sixty eight of 228 students participated, (response rate of 29.8%). No statistical difference was found between gender (p=0.090); a statistically significant difference was found between year (p=0.008). Cronbach's alpha (0.809) confirmed a good internal consistency. 97.0% of the students learned a lot, and 85.3% appreciated and valued the PAT sessions; 89.7% wanted more sessions. 92.7% perceived the sessions to contextualize their learning. Five questions were dichotomized by grouping the responses into negative and positive; 90.3% of responses were positive and did not show statistically significant differences in gender and year of study. Overall students' free text comments were positive, but active listening and consultation appeared in the positive and negative domains, highlighting the need for more student engagement. CONCLUSIONS: PAT sessions had a positive impact on students' knowledge, communication skills, and participation, and contextualized learning. They provide a valuable contribution to the pharmcy students' experience in the United Kingdom.

Peritoneal Dialysis Catheter Removal Post-Transplant - A Rare Case of Delayed Bowel Perforation.

Peritoneal dialysis (PD) is a well-established form of renal replacement therapy and the practice of leaving catheters in situ post-transplantation widely accepted. We present a rare complication: a child presenting with anal protrusion of the PD catheter.The patient is an 11-year-old boy with a background of renal dysplasia and congenital cutis laxa. Twenty-three weeks after dialysis was commenced, the patient underwent a renal transplant. Thirteen weeks post-transplant, the patient felt an unusual sensation after defecation. The curled end of the catheter was seen protruding from the anus. He was admitted, and investigations showed stable graft function, with abdominal X ray showing no free air.Intraoperative findings showed a small perforation of the sigmoid colon sealed off by adherence of several small intestinal loops. This was repaired laparoscopically after removal of the distal part of the catheter per rectum. No peritoneal contamination was seen. He was treated with 5 days of intravenous antibiotics and gradual introduction of enteral feeds. His graft function remained stable throughout.Timing of catheter removal varies, from the time of transplantation to over 3 months post-transplantation. Bowel perforation due to PD catheter insertion is rare and tends to occur at the time of insertion. Anal protrusion of a PD catheter in childhood is extremely rare and unrecorded in a pediatric patient with a connective tissue disorder. Our case highlights that serious complications can occur in the period between transplantation and elective PD catheter removal and that, in the immunocompromised patient, signs can be subtle.