Plan-do-study-act (PDSA) interventions to improve real-world endoscopy unit productivity.

Background and study aims The Plan-Do-Study Act (PDSA) ramp is a framework that uses initial small changes to build consensus and momentum for subsequent, iterative process improvement. Our aim was to study its impact on endoscopy unit efficiency and throughput. Methods Following a granular time-and-motion analysis to evaluate baseline performance (phase 1) we instituted successive interventions and measured their impact on core efficiency metrics including procedure volume and turnover time (phases 2-3). Results We identified that inefficiency in turnover of anesthesia-supported endoscopy was the most crucial issue. Implementation of a pre-procedure anesthesia visit in phase 2 reduced turnover time by 15.5 minutes (95% confidence interval 3.9-27.1 minutes). Subsequent changes (phase 3) including front-loaded procedure scheduling and parallel in-room preparation resulted in an 18% increase in procedure volume. Conclusions The PDSA ramp model is an effective means of assessing operational processes, developing novel interventions, and building consensus to improve the real-world productivity in a resource-conscious manner.

Comparative effectiveness between two types of head-mounted magnification modes using a smartphone-based virtual display.

SIGNIFICANCE: This work shows the benefits of using two different magnification strategies to improve the reading ability of low-vision patients using a head-mounted technology. PURPOSE: The aim of this study was to conduct a comparative clinical trial evaluating the effectiveness of two magnification strategies in a head-mounted virtual reality display. METHODS: Eighty-eight eligible low-vision subjects were randomized into two arms: (1) the full-field magnification display or (2) the virtual bioptic telescope mode. Subjects completed baseline testing and received training on how to use the device properly and then took the device home for a 2- to 4-week intervention period. An adaptive rating scale questionnaire (Activity Inventory) was administered before and after the intervention (home trial) period to measure the effect of the system. A Simulator Sickness Questionnaire was also administered. Baseline and follow-up results were analyzed using Rasch analysis to assess overall effectiveness of each magnification mode for various functional domain categories. RESULTS: Both magnification modes showed a positive effect for reading, visual information, and the overall goals functional domain categories, with only reading reaching statistical significance after correction for multiple comparisons. However, there were no significant between-group differences between the two modes. The results of the Simulator Sickness Questionnaire showed that the magnification modes of the head-mounted display device were overall well tolerated among low-vision users. CONCLUSIONS: Both the full-field and virtual bioptic magnification strategies were effective in significantly improving functional vision outcomes for self-reported reading ability.

Bed-rest and exercise remobilization: Concurrent adaptations in muscle glucose and protein metabolism.

BACKGROUND: Bed-rest (BR) of only a few days duration reduces muscle protein synthesis and induces skeletal muscle atrophy and insulin resistance, but the scale and juxtaposition of these events have not been investigated concurrently in the same individuals. Moreover, the impact of short-term exercise-supplemented remobilization (ESR) on muscle volume, protein turnover and leg glucose uptake (LGU) in humans is unknown. METHODS: Ten healthy males (24 ± 1 years, body mass index 22.7 ± 0.6 kg/m2) underwent 3 days of BR, followed immediately by 3 days of ESR consisting of 5 × 30 maximal voluntary single-leg isokinetic knee extensions at 90°/s each day. An isoenergetic diet was maintained throughout the study (30% fat, 15% protein and 55% carbohydrate). Resting LGU was calculated from arterialized-venous versus venous difference across the leg and leg blood flow during the steady-state of a 3-h hyperinsulinaemic-euglycaemic clamp (60 mU/m2/min) measured before BR, after BR and after remobilization. Glycogen content was measured in vastus lateralis muscle biopsy samples obtained before and after each clamp. Leg muscle volume (LMV) was measured using magnetic resonance imaging before BR, after BR and after remobilization. Cumulative myofibrillar protein fractional synthetic rate (FSR) and whole-body muscle protein breakdown (MPB) were measured over the course of BR and remobilization using deuterium oxide and 3-methylhistidine stable isotope tracers that were administered orally. RESULTS: Compared with before BR, there was a 45% decline in insulin-stimulated LGU (P < 0.05) after BR, which was paralleled by a reduction in insulin-stimulated leg blood flow (P < 0.01) and removal of insulin-stimulated muscle glycogen storage. These events were accompanied by a 43% reduction in myofibrillar protein FSR (P < 0.05) and a 2.5% decrease in LMV (P < 0.01) during BR, along with a 30% decline in whole-body MPB after 2 days of BR (P < 0.05). Myofibrillar protein FSR and LMV were restored by 3 days of ESR (P < 0.01 and P < 0.01, respectively) but not by ambulation alone. However, insulin-stimulated LGU and muscle glycogen storage were not restored by ESR. CONCLUSIONS: Three days of BR caused concurrent reductions in LMV, myofibrillar protein FSR, myofibrillar protein breakdown and insulin-stimulated LGU, leg blood flow and muscle glycogen storage in healthy, young volunteers. Resistance ESR restored LMV and myofibrillar protein FSR, but LGU and muscle glycogen storage remained depressed, highlighting divergences in muscle fuel and protein metabolism. Furthermore, ambulation alone did not restore LMV and myofibrillar protein FSR in the non-exercised contralateral limb, emphasizing the importance of exercise rehabilitation following even short-term BR.

Prospective, randomised, parallel-group, open-label study to evaluate the effectiveness and safety of IMU-838, in combination with oseltamivir, in adults with COVID-19: the IONIC trial protocol.

BACKGROUND: Globally, there is a scarcity of effective treatments for SARS-CoV-2 infections (causing COVID-19). Repurposing existing medications may offer the best hope for treating patients with COVID-19 to curb the pandemic. IMU-838 is a dihydroorotate dehydrogenase inhibitor, which is an effective mechanism for antiviral effects against respiratory viruses. When used synergistically with oseltamivir, therapeutic effects have been observed against influenza and SARS-CoV-2 in rodents. The IMU-838 and Oseltamivir in the Treatment of COVID-19 (IONIC) trial is a randomised controlled trial that will investigate whether time to clinical improvement in patients with COVID-19 is improved following a 14-day course of IMU-838+oseltamivir versus oseltamivir alone. METHODS: IONIC trial is an open-label study in which participants will be randomised 1:1 in two parallel arms: the intervention arm (IMU-838+oseltamivir) and the control arm (oseltamivir only). The primary outcome is time to clinical improvement; defined as the time from randomisation to a two-point improvement on WHO ordinal scale; discharge from hospital, or death (whichever occurs first). The study is sponsored by the University Hospitals Coventry and Warwickshire NHS Trust and funded by LifeArc. DISCUSSION: The IONIC protocol describes an overarching trial design to provide reliable evidence on the effectiveness of IMU-838 (vidofludimus calcium) when delivered in combination with an antiviral therapy (oseltamivir) (IONIC intervention) for confirmed or suspected COVID-19 infection in adult patients receiving usual standard of care. ETHICS AND DISSEMINATION: This study has been independently reviewed and approved by Wales Research Ethics Committee. In addition, required regulatory approvals were received from Medicines and Healthcare products Regulatory Agency. TRIAL REGISTRATION NUMBER: EudraCT 2020-001805-21, ISRCTN53038326, NCT04516915.

Variability of noninvasive MRI and biological markers in compensated cirrhosis: insights for assessing disease progression.

BACKGROUND: We annually monitored stable compensated cirrhosis (CC) patients to evaluate serial variation in blood serum, liver stiffness, and multiparametric magnetic resonance imaging (mpMRI) measures to provide reference change values (RCV) and sample size measures for future studies. METHODS: Patients were recruited from a prospectively followed CC cohort, with assessments at baseline and annually over three years. We report on blood markers, transient elastography liver stiffness measures (LSM) and noninvasive mpMRI (volume, T1 mapping, blood flow, perfusion) of the liver, spleen, kidneys, and heart in a stable CC group and a healthy volunteer (HV) group. Coefficient of variation over time (CoVT) and RCV are reported, along with hazard ratio to assess disease progression. Sample size estimates to power future trials of cirrhosis regression on mpMRI are presented. RESULTS: Of 60 CC patients enrolled, 28 with stable CC were followed longitudinally and compared to 10 HVs. CoVT in mpMRI measures was comparable between CC and HV groups. CoVT of Enhanced Liver Fibrosis score was low (< 5%) compared to Fibrosis-4 index (17.9%) and Aspartate Aminotransferase-to-Platelet-Ratio Index (19.4%). A large CoVT (20.7%) and RCV (48.3%) were observed for LSM. CoVT and RCV were low for liver, spleen, and renal T1 values (CoVT < 5%, RCV < 8%) and volume (CoVT < 10%, RCV < 16%); haemodynamic measures were high (CoVT 12-25%, RCV 16-47%). CONCLUSIONS: Evidence of low CoVT and RCV in multiorgan T1 values. RCV and sample size estimates are provided for future longitudinal multiorgan monitoring in CC patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02037867 , Registered: 05/01/2013.

Implantable Cardioverter-defibrillator Magnetic Interference by the iPhone 12: Is It Clinically Significant?

The iPhone 12 series (Apple, Inc., Cupertino, CA, USA) contains a circular array of magnets around a central charging coil (compatible with "Magsafe" technology). The device was recently reported to have magnetic interference with implantable cardioverter-defibrillators (ICDs). We sought to test the electromagnetic interference of the iPhone 12 in inhibiting life-saving therapies of ICDs in clinical settings. After obtaining written informed consent, an iPhone 12 was placed over the device generators of 17 patients in the ICD clinic. Device interrogation was performed immediately before and after placing the iPhone over the ICD generator to evaluate for any inhibition of device therapies. To emulate a real-world scenario, the iPhone 12 was not placed directly over the skin above the device generator but instead was positioned over the patients' clothes. None of the device interrogations revealed interruption of device therapies due to the iPhone. We concluded that, despite the iPhone having shown in vitro interference of ICD functioning, its effects are not clinically relevant in vivo. Larger studies need to be performed to confirm this finding and guide safety recommendations regarding the use of iPhones containing magnets by patients with implanted ICDs.

Dearth of electrophysiology fellows: perspectives from cardiology fellows-in-training.

BACKGROUND: Over the last 6 years, there has been a high percentage of unfilled cardiac electrophysiology (EP) training spots each year. The authors aimed to investigate potential explanations for the unfilled positions based on a survey from the current Fellows-In-Training (FITs). METHODS: An attempt was made to reach the current cardiology FITs across all programs of the U.S. via email. An anonymous questionnaire was created consisting of 14 questions. Questions posed were regarding factors affecting each participant's interest in or lack of pursuing an EP fellowship. Descriptive statistics of the responses were performed. RESULTS: A total of 26% (35/134) respondents expressed their interest in applying to an EP fellowship. The most common reasons to apply to EP were: Interest in EP, procedural specialty, and work-life balance. Of the 99 respondents that were not applying to EP, the most common reasons not to apply were: Less interest in EP, two-year training duration, and complexity of the specialty. The top reasons for the fellows to believe there is a dearth of EP FITs were: two-year training duration, lack of interest in EP, and the complexity of the specialty. The changes that would encourage EP fellowship interest were: More exposure to EP training during general cardiology fellowship, shortening the EP training duration, and having more information available regarding employment opportunities. CONCLUSION: The study was able to identify factors responsible for vacancies in EP fellowship positions from the view of current cardiology FITs. Stakeholders at the national level involved in framing policies related to fellowship education would be able to utilize this information to address the shortage of EP FITs and increase recruitment to EP fellowships.

REducing Colonoscopies in patients without significant bowEl DiseasE: the RECEDE Study - protocol for a prospective diagnostic accuracy study.

INTRODUCTION: Demand for colonoscopies and CT colonography (CTC) is exceeding capacity in National Health Service Trusts. In many patients colonoscopies and CTCs show no significant bowel disease (SBD). Faecal Immunochemical Testing (FIT) is being introduced to prioritise patients for colonoscopies but is insufficient to identify non-SBD patients meaning colonoscopy and CTC demand remains high. The REducing Colonoscopies in patients without significant bowEl DiseasE (RECEDE) study aims to test urine volatile organic compound (VOC) analysis alongside FIT to improve detection of SBD and to reduce the number of colonoscopies and CTCs. METHODS AND ANALYSIS: This is a multicentre, prospective diagnostic accuracy study evaluating whether stool FIT plus urine VOC compared with stool FIT alone improves detection of SBD in patients referred for colonoscopy or CTC due to persistent lower gastrointestinal symptoms. To ensure SBD is not missed, the dual test requires a high sensitivity, set at 97% with 95% CI width of 5%. Our assumption is that to achieve this sensitivity requires 200 participants with SBD. Further assuming 19% of all participants will have SBD and 55% of all participants will return both stool and urine samples we will recruit 1915 participants. The thresholds for FIT and VOC results diagnosing SBD have been pre-set. If either FIT or VOC exceeds the respective threshold, the participant will be classed as having suspected SBD. As an exploratory analysis we will be testing different thresholds. The reference comparator will be a complete colonoscopy or CTC. Secondary outcomes will look at optimising the FIT and VOC thresholds for SBD detection. An economic evaluation, using a denovo decision analytic model, will be carried out determine the costs, benefits and overall cost-effectiveness of FIT +VOC vs FIT followed by colonoscopy. ETHICS AND DISSEMINATION: Ethical approval was obtained by Liverpool Central Research Ethics Committee (20/NW/0346). TRIAL REGISTRATION NUMBER: RECEDE is registered on Clinicaltrials.gov NCT04516785 & ISRCTN14982373. This protocol was written and published before results of the trial were available.

An integrative multiscale view of early cardiac looping.

The heart is the first organ to form and function during the development of an embryo. Heart development consists of a series of events believed to be highly conserved in vertebrates. Development of heart begins with the formation of the cardiac fields followed by a linear heart tube formation. The straight heart tube then undergoes a ventral bending prior to further bending and helical torsion to form a looped heart. The looping phase is then followed by ballooning, septation, and valve formation giving rise to a four-chambered heart in avians and mammals. The looping phase plays a central role in heart development. Successful looping is essential for proper alignment of the future cardiac chambers and tracts. As aberrant looping results in various congenital heart diseases, the mechanisms of cardiac looping have been studied for several decades by various disciplines. Many groups have studied anatomy, biology, genetics, and mechanical processes during heart looping, and have proposed multiple mechanisms. Computational modeling approaches have been utilized to examine the proposed mechanisms of the looping process. Still, the exact underlying mechanism(s) controlling the looping phase remain poorly understood. Although further experimental measurements are obviously still required, the need for more integrative computational modeling approaches is also apparent in order to make sense of the vast amount of experimental data and the complexity of multiscale developmental systems. Indeed, there needs to be an iterative interaction between experimentation and modeling in order to properly find the gap in the existing data and to validate proposed hypotheses. This article is categorized under: Cardiovascular Diseases > Genetics/Genomics/Epigenetics Cardiovascular Diseases > Computational Models Cardiovascular Diseases > Molecular and Cellular Physiology.

Postexercise urinary alpha-1 acid glycoprotein is not dependent on hypoxia.

Proteinuria is a transient physiological phenomenon that occurs with a range of physical activities and during ascent to altitude. Exercise intensity appears to dictate the magnitude of postexercise proteinuria; however, evidence also indicates the possible contributions from exercise-induced hypoxemia or reoxygenation. Using an environmental hypoxic chamber, this crossover-designed study aimed to evaluate urinary alpha-1 acid glycoprotein (α1-AGP) excretion pre/postexercise performed in hypoxia (HYP) and normoxia (NOR). Sixteen individuals underwent experimental sessions in normoxia (NOR, 20.9% O2) and hypoxia (HYP, 12.0% O2). Sessions began with a 2-h priming period before completing a graded maximal exercise test (GXT) on a cycle ergometer, which was followed by continuation of exposure for an additional 2 h. Physiological responses (i.e., blood pressure, heart rate, and peripheral oxygenation), Lake Louise Scores (LLSs), and urine specimens (analyzed for albumin and α1-AGP) were collected pre- and postexercise (after 30, 60, and 120 min). Peak power output was significantly reduced in HYP (193 ± 45 W) compared with NOR (249 ± 59 W, P < 0.01). Postexercise urinary α1-AGP was greater in NOR (20.04 ± 14.84 µg·min-1) than in HYP (15.08 ± 13.46 µg·min-1), albeit the difference was not significant (P > 0.05). Changes in urinary α1-AGP from pre- to post-30 min were not related to physiological responses or performance outcomes observed during GXT in NOR or HYP. Despite profound systemic hypoxemia with maximal exercise in hypoxia, postexercise α1-AGP excretion was not elevated above the levels observed following normoxic exercise.NEW & NOTEWORTHY By superimposing hypoxic exposure and maximal exercise, we were able to investigate the impact of hypoxia on postexercise proteinuria. Urinalysis for α1-AGP (via particle-enhanced immunoturbidimetry) in specimens collected pre-/postexercise enabled the sensitive detection of altered glomerular permeability. Data indicated that exercise intensity, rather than the degree of exercise-induced hypoxemia, determines postexercise proteinuria.

A governing equation for rotor and wavelet number in human clinical ventricular fibrillation: Implications for sudden cardiac death.

BACKGROUND: Ventricular fibrillation (VF) is characterized by multiple wavelets and rotors. No equation to predict the number of rotors and wavelets observed during fibrillation has been validated in human VF. OBJECTIVE: The purpose of this study was to test the hypothesis that a single equation derived from a Markov M/M/∞ birth-death process could predict the number of rotors and wavelets occurring in human clinical VF. METHODS: Epicardial induced VF (256-electrode) recordings obtained from patients undergoing cardiac surgery were studied (12 patients; 62 epochs). Rate constants for phase singularity (PS) (which occur at the pivot points of rotors) and wavefront (WF) formation and destruction were derived by fitting distributions to PS and WF interformation and lifetimes. These rate constants were combined in an M/M/∞ governing equation to predict the number of PS and WF in VF episodes. Observed distributions were compared to those predicted by the M/M/∞ equation. RESULTS: The M/M/∞ equation accurately predicted average PS and WF number and population distribution, demonstrated in all epochs. Self-terminating episodes of VF were distinguished from VF episodes requiring termination by a trend toward slower PS destruction, slower rates of PS formation, and a slower mixing rate of the VF process, indicated by larger values of the second largest eigenvalue modulus of the M/M/∞ birth-death matrix. The longest-lasting PS (associated with rotors) had shorter interactivation time intervals compared to shorter-lasting PS lasting <150 ms (∼1 PS rotation in human VF). CONCLUSION: The M/M/∞ equation explains the number of wavelets and rotors observed, supporting a paradigm of VF based on statistical fibrillatory dynamics.

Evaluation of photography using head-mounted display technology (ICAPS) for district Trachoma surveys.

BACKGROUND: As the prevalence of trachoma declines worldwide, it is becoming increasingly expensive and challenging to standardize graders in the field for surveys to document elimination. Photography of the tarsal conjunctiva and remote interpretation may help alleviate these challenges. The purpose of this study was to develop, and field test an Image Capture and Processing System (ICAPS) to acquire hands-free images of the tarsal conjunctiva for upload to a virtual reading center for remote grading. METHODOLOGY/PRINCIPAL FINDINGS: This observational study was conducted during a district-level prevalence survey for trachomatous inflammation-follicular (TF) in Chamwino, Tanzania. The ICAPS was developed using a Samsung Galaxy S8 smartphone, a Samsung Gear VR headset, a foot pedal trigger and customized software allowing for hands-free photography. After a one-day training course, three trachoma graders used the ICAPS to collect images from 1305 children ages 1-9 years, which were expert-graded remotely for comparison with field grades. In our experience, the ICAPS was successful at scanning and assigning barcodes to images, focusing on the everted eyelid with adequate examiner hand visualization, and capturing images with sufficient detail to grade TF. The percentage of children with TF by photos and by field grade was 5%. Agreement between grading of the images compared to the field grades at the child level was kappa = 0.53 (95%CI = 0.40-0.66). There were ungradable images for at least one eye in 199 children (9.1%), with more occurring in children ages 1-3 (18.5%) than older children ages 4-9 (4.2%) (χ2 = 145.3, p<0.001). CONCLUSIONS/SIGNIFICANCE: The prototype ICAPS device was robust, able to image 1305 children in a district level survey and transmit images from rural Tanzania to an online grading platform. More work is needed to improve the percentage of ungradable images and to better understand the causes of disagreement between field and photo grading.

In silicoevaluation and optimisation of magnetic resonance elastography of the liver.

Objective.Magnetic resonance elastography (MRE) is widely adopted as a biomarker of liver fibrosis. However,in vivoMRE accuracy is difficult to assess.Approach.Finite element model (FEM) simulation was employed to evaluate liver MRE accuracy and inform methodological optimisation. MRE data was simulated in a 3D FEM of the human torso including the liver, and compared with spin-echo echo-planar imaging MRE acquisitions. The simulated MRE results were compared with the ground truth magnitude of the complex shear modulus (∣G*∣) for varying: (1) ground truth liver ∣G*∣; (2) simulated imaging resolution; (3) added noise; (4) data smoothing. Motion and strain-based signal-to-noise (SNR) metrics were evaluated on the simulated data as a means to select higher-quality voxels for preparation of acquired MRE summary statistics of ∣G*∣.Main results.The simulated MRE accuracy for a given ground truth ∣G*∣ was found to be a function of imaging resolution, motion-SNR and smoothing. At typical imaging resolutions, it was found that due to under-sampling of the MRE wave-field, combined with motion-related noise, the reconstructed simulated ∣G*∣ could contain errors on the scale of the difference between liver fibrosis stages, e.g. 54% error for ground truth ∣G*∣ = 1 kPa. Optimum imaging resolutions were identified for given ground truth ∣G*∣ and motion-SNR levels.Significance.This study provides important knowledge on the accuracy and optimisation of liver MRE. For example, for motion-SNR ≤ 5, to distinguish between liver ∣G*∣ of 2 and 3 kPa (i.e. early-stage liver fibrosis) it was predicted that the optimum isotropic voxel size is 4-6 mm.

Intrinsic and extrinsic apoptosis responses in leukaemia cells following daunorubicin treatment.

BACKGROUND: Daunorubicin is used clinically in the treatment of myeloma, acute lymphatic and myelocytic leukaemia. The toxic lesions caused by daunorubicin induce various modes of cell death, including apoptosis. Apoptosis is highly regulated programmed cell death that can be initiated mainly via two pathways, through death receptors (extrinsic) or involvement of the mitochondria (intrinsic). Induction of apoptosis via these pathways has been alluded following treatment with daunorubicin, but never compared in acute lymphoblastic leukaemia over a time course. METHODS: This study investigated the mechanisms of daunorubicin induced apoptosis in the treatment of CCRF-CEM, MOLT-4 (acute T-lymphoblastic leukaemia) and SUP-B15 (acute B-lymphoblastic leukaemia) cells. Cells were treated with daunorubicin for 4 h, and then placed in recovery medium (without daunorubicin) for 4 h, 12 h and 24 h. Apoptotic response was analysing using annexin-V expression, caspase activity, mitochondrial membrane potential change and an array to detect 43 apoptotic proteins. RESULTS: Daunorubicin induced apoptosis in all leukemic cell lines, but with different levels and duration of response. Both apoptosis levels and caspase activity increased after four hours recovery then declined in CCRF-CEM and MOLT-4 cells. However, SUP-B15 cells displayed initially comparable levels but remained elevated over the 24 h assessment period. Changes in mitochondrial membrane potential occurred in both MOLT-4 and CCRF-CEM cells but not in SUP-B15 cells. Expression of apoptotic proteins, including Bcl-2, Bax, caspase 3 and FADD, indicated that daunorubicin potentially induced both extrinsic and intrinsic apoptosis in both CCRF-CEM and MOLT-4 cells, but only extrinsic apoptosis in SUP-B15 cells. CONCLUSIONS: This study describes variations in sensitivities and timing of apoptotic responses in different leukaemia cell lines. These differences could be attributed to the lack of functional p53 in coordinating the cells response following cytotoxic treatment with daunorubicin, which appears to delay apoptosis and utilises alternative signalling mechanisms that need to be further explored.

Effects on childhood infections of promoting safe and hygienic complementary-food handling practices through a community-based programme: A cluster randomised controlled trial in a rural area of The Gambia.

BACKGROUND: The Gambia has high rates of under-5 mortality from diarrhoea and pneumonia, peaking during complementary-feeding age. Community-based interventions may reduce complementary-food contamination and disease rates. METHODS AND FINDINGS: A public health intervention using critical control points and motivational drivers, delivered February-April 2015 in The Gambia, was evaluated in a cluster randomised controlled trial at 6- and 32-month follow-up in September-October 2015 and October-December 2017, respectively. After consent for trial participation and baseline data were collected, 30 villages (clusters) were randomly assigned to intervention or control, stratified by population size and geography. The intervention included a community-wide campaign on days 1, 2, 17, and 25, a reminder visit at 5 months, plus informal community-volunteer home visits. It promoted 5 key complementary-food and 1 key drinking-water safety and hygiene behaviours through performing arts, public meetings, and certifications delivered by a team from local health and village structures to all villagers who attended the activities, to which mothers of 6- to 24-month-old children were specifically invited. Control villages received a 1-day campaign on domestic-garden water use. The background characteristics of mother and clusters (villages) were balanced between the trial arms. Outcomes were measured at 6 and 32 months in a random sample of 21-26 mothers per cluster. There were no intervention or research team visits to villages between 6 and 32 months. The primary outcome was a composite outcome of the number of times key complementary-food behaviours were observed as a proportion of the number of opportunities to perform the behaviours during the observation period at 6 months. Secondary outcomes included the rate of each recommended behaviour; microbiological growth from complementary food and drinking water (6 months only); and reported acute respiratory infections, diarrhoea, and diarrhoea hospitalisation. Analysis was by intention-to-treat analysis adjusted by clustering. (Registration: PACTR201410000859336). We found that 394/571 (69%) of mothers with complementary-feeding children in the intervention villages were actively involved in the campaign. No villages withdrew, and there were no changes in the implementation of the intervention. The intervention improved behaviour adoption significantly. For the primary outcome, the rate was 662/4,351(incidence rate [IR] = 0.15) in control villages versus 2,861/4,378 (IR = 0.65) in intervention villages (adjusted incidence rate ratio [aIRR] = 4.44, 95% CI 3.62-5.44, p < 0.001), and at 32 months the aIRR was 1.17 (95% CI 1.07-1.29, p = 0.001). Secondary health outcomes also improved with the intervention: (1) mother-reported diarrhoea at 6 months, with adjusted relative risk (aRR) = 0.39 (95% CI 0.32-0.48, p < 0.001), and at 32 months, with aRR = 0.68 (95% CI 0.48-0.96, p = 0.027); (2) mother-reported diarrhoea hospitalisation at 6 months, with aRR = 0.35 (95% CI 0.19-0.66, p = 0.001), and at 32 months, with aRR = 0.38 (95% CI 0.18-0.80, p = 0.011); and (3) mother-reported acute respiratory tract infections at 6 months, with aRR = 0.67 (95% CI 0.53-0.86, p = 0.001), though at 32 months improvement was not significant (p = 0.200). No adverse events were reported. The main limitations were that only medium to small rural villages were involved. Obtaining laboratory cultures from food at 32 months was not possible, and no stool microorganisms were investigated. CONCLUSIONS: We found that low-cost and culturally embedded behaviour change interventions were acceptable to communities and led to short- and long-term improvements in complementary-food safety and hygiene practices, and reported diarrhoea and acute respiratory tract infections. TRIAL REGISTRATION: The trial was registered on the 17th October 2014 with the Pan African Clinical Trial Registry in South Africa with number (PACTR201410000859336) and 32-month follow-up as an amendment to the trial.

Hydroxychloroquine/Azithromycin Therapy and QT Prolongation in Hospitalized Patients With COVID-19.

OBJECTIVES: This study aimed to characterize corrected QT (QTc) prolongation in a cohort of hospitalized patients with coronavirus disease-2019 (COVID-19) who were treated with hydroxychloroquine and azithromycin (HCQ/AZM). BACKGROUND: HCQ/AZM is being widely used to treat COVID-19 despite the known risk of QT interval prolongation and the unknown risk of arrhythmogenesis in this population. METHODS: A retrospective cohort of COVID-19 hospitalized patients treated with HCQ/AZM was reviewed. The QTc interval was calculated before drug administration and for the first 5 days following initiation. The primary endpoint was the magnitude of QTc prolongation, and factors associated with QTc prolongation. Secondary endpoints were incidences of sustained ventricular tachycardia or ventricular fibrillation and all-cause mortality. RESULTS: Among 415 patients who received concomitant HCQ/AZM, the mean QTc increased from 443 ± 25 ms to a maximum of 473 ± 40 ms (87 [21%] patients had a QTc ≥500 ms). Factors associated with QTc prolongation ≥500 ms were age (p < 0.001), body mass index <30 kg/m2 (p = 0.005), heart failure (p < 0.001), elevated creatinine (p = 0.005), and peak troponin (p < 0.001). The change in QTc was not associated with death over the short period of the study in a population in which mortality was already high (hazard ratio: 0.998; p = 0.607). No primary high-grade ventricular arrhythmias were observed. CONCLUSIONS: An increase in QTc was seen in hospitalized patients with COVID-19 treated with HCQ/AZM. Several clinical factors were associated with greater QTc prolongation. Changes in QTc were not associated with increased risk of death.

Protocol driven periprocedural anticoagulation for left atrial ablation.

INTRODUCTION: A weight-based heparin dosing policy adjusted for preprocedural oral anticoagulation was implemented to reduce the likelihood of subtherapeutic dosing during left atrial catheter ablation procedures. We hypothesized that initiation of the protocol would result in a greater prevalence of therapeutic activated clotting time (ACT) values and decreased time to therapeutic ACT during left atrial ablation procedures. METHODS: A departmental protocol was initiated for which subjects received intravenous unfractionated heparin (UFH) to achieve and maintain a goal of ACT >300 s. Initial bolus dose was adjusted for pre-procedure oral anticoagulation and weight as follows: 50 units/kg for those receiving warfarin, 75 units/kg for those not anticoagulated, and 120 units/kg for those on direct oral anticoagulants (DOACs). A UFH infusion was initiated at 10% of the bolus per hour. One hundred consecutive left atrial ablation procedures treated with Protocol Guided heparin dosing were compared with a retrospective consecutive cohort of Usual Care heparin dosing. RESULTS: When the Usual Care and Protocol Guided cohorts were compared, significant findings were limited to those on pre-procedure DOAC. The initial UFH bolus increased from 99.3 ± 24.8 to 118.2 ± 22.8 units/kg (p < .001), the proportion of therapeutic ACT on the first draw after heparin administration increased from 57.7% to 76.6% (p = .010), and the time to therapeutic ACT after UFH administration decreased from 37.8 ± 19.8 to 30.2 ± 16.4 min (p = .032). CONCLUSION: A weight-based protocol for periprocedural UFH administration resulted in a higher proportion of therapeutic ACT values and decreased the time to therapeutic ACT for those on pre-procedure DOAC.

The MRI colonic function test: Reproducibility of the Macrogol stimulus challenge.

BACKGROUND: Magnetic resonance imaging (MRI) of the colonic response to a macrogol challenge drink can be used to assess the mechanisms underlying severe constipation. We measured the intrasubject reproducibility of MRI measures of colonic function to aid their implementation as a possible clinical test. METHODS: Healthy participants attended for MRI on two occasions (identical protocols, minimum 1 week apart). They underwent a fasted scan and then consumed the macrogol drink. Subjects were scanned at 60 and 120 minutes, with maximum value reached used for comparison. The colonic volume, water content, mixing of colonic content and the movement of the colon walls were measured. Coefficients of variation and intraclass correlation coefficients (ICC) were calculated. RESULTS: Twelve participants completed the study: nine female, mean age 26 years (SD 5) and body mass index 24.8 kg/m2 (SD 3.2). All measures consistently increased above baseline following provocation with macrogol. The volume, water content and content mixing had good intrasubject reproducibility (ICC volume = 0.84, water content = 0.93, mixing = 0.79, P < .001). With the wall movement, the response to the challenge was generally large, but more variable between visits resulting in a lower ICC overall (ascending colon = 0.65, descending colon = 0.76, P < .001). CONCLUSIONS: The colonic response to the macrogol stimulus as assessed by MRI is heterogeneous but large compared to baseline, with moderate to good reproducibility, making the test suitable to study potential pathologies underlying GI disorders such as constipation. More data are needed to better define the normal range for comparison with patient groups who may have both hypo- and hypermotile responses.

Woven Natural Fibre Reinforced Composite Materials for Medical Imaging.

Repeatable patient positioning is key to minimising the burden on planning radiotherapy treatment. There are very few materials commercially available which are suitable for use in all common imaging and treatment modalities such as magnetic resonance imaging (MRI), X-Ray computed tomography (CT) and radiotherapy. In this article, we present several such materials based on woven natural fibres embedded in a range of different resin materials which are suitable for such applications. By investigating a range of resins and natural fibre materials in combination and evaluating their performance in terms of MRI and X-Ray imaging, we show that a woven cotton material impregnated with a two-part epoxy resin provides a 15% improvement in passage of X-Rays and has no impact on the MRI signal (unlike the 40% MRI signal attenuation from carbon fibre), whilst also retaining a flexural modulus up to 71% of that of carbon fibre. These results demonstrate that natural fibre composites produced using such materials provide desirable properties for use in patient support and positioning devices for multi-modal imaging, without the need to significantly compromise on the strength of the material.