JURNAL AGROTEKNOLOGI
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Left atrial strain predicts cardiovascular response to exercise in young adults with suboptimal blood pressure
No full textAims
To investigate the left ventricular response to exercise in young adults with hypertension, and identify whether this response can be predicted from changes in left atrial function at rest.
Methods
A total of 127 adults aged 18–40 years who completed clinical blood pressure assessment and echocardiography phenotyping at rest and during cardiopulmonary exercise testing, were included. Measurements were compared between participants with suboptimal blood pressure ≥120/80mm Hg (n = 68) and optimal blood pressure <120/80mm Hg (n = 59). Left ventricular systolic function during exercise was obtained from an apical four chamber view, while resting left atrial function was assessed from apical four and two chamber views.
Results
Participants with suboptimal blood pressure had higher left ventricular mass (p = 0.031) and reduced mitral E velocity (p = 0.02) at rest but no other cardiac differences. During exercise, their rise in left ventricular ejection fraction was reduced (p = 0.001) and they had higher left ventricular end diastolic and systolic volumes (p = 0.001 and p = 0.001, respectively). Resting cardiac size predicted left ventricular volumes during exercise but only left atrial booster pump function predicted the left ventricular ejection fraction response (urn:x-wiley:07422822:media:echo15149:echo15149-math-0001= .29, p = 0.011). This association persisted after adjustment for age, sex, body mass index, and mean arterial pressure.
Conclusion
Young adults with suboptimal blood pressure have a reduced left ventricular systolic response to exercise, which can be predicted by their left atrial booster pump function at rest. Echocardiographic measures of left atrial function may provide an early marker of functionally relevant, subclinical, cardiac remodelling in young adults with hypertension
Determinants of primaquine and carboxyprimaquine exposures in children and adults with Plasmodium vivax malaria
No full textBackground
Primaquine is the only widely available drug for radical cure of Plasmodium vivax malaria. There is uncertainty whether the pharmacokinetic properties of primaquine are altered significantly in childhood or not.
Methods
Glucose-6-phosphate dehydrogenase normal patients with uncomplicated P. vivax malaria were randomized to receive either chloroquine (25mg base/kg) or dihydroartemisinin-piperaquine (dihydroartemisinin 7mg/kg and piperaquine 55mg/kg) plus primaquine; given either as 0.5 mg base/kg/day for 14 days or 1 mg/kg/day for 7 days. Pre-dose day 7 venous plasma concentrations of chloroquine, desethylchloroquine, piperaquine, primaquine and carboxyprimaquine were measured. Methemoglobin levels were measured on day 7.
Results
Day 7 primaquine and carboxyprimaquine concentrations were available for 641 patients. After adjustment for the primaquine mg/kg daily dose, day of sampling, partner drug, and fever clearance, there was a significant non-linear relationship between age and trough primaquine and carboxyprimaquine concentrations, and day methemoglobin levels. Compared to adults 30 years of age, children 5 years of age had trough primaquine concentrations 0.53 (95% CI: 0.39- 0.73) fold lower, trough carboxyprimaquine concentrations 0.45 (95% CI: 0.35- 0.55) fold lower, and day 7 methemoglobin levels 0.87 (95% CI: 0.58-1.27) fold lower. Increasing concentrations of piperaquine and chloroquine and poor metabolizer CYP 2D6 alleles were associated with higher day 7 primaquine and carboxyprimaquine concentrations. Higher blood methemoglobin concentrations were associated with a lower risk of recurrence.
Conclusion
Young children have lower primaquine and carboxyprimaquine exposures, and lower levels of methemoglobinemia, than adults. Young children may need higher weight adjusted primaquine doses than adults
An optically heated atomic source for compact ion trap vacuum systems
No full textWe present a design for an atomic oven suitable for loading ion traps, which is operated via optical heating with a continuous-wave multimode diode laser. The absence of the low-resistance electrical connections necessary for Joule heating allows the oven to be extremely well thermally isolated from the rest of the vacuum system. Extrapolating from high-flux measurements of an oven filled with calcium, we calculate that a target region number density of 100 cm−3, suitable for rapid ion loading, will be produced with 175(10) mW of heating laser power, limited by radiative losses. With simple feedforward to the laser power, the turn-on time for the oven is 15 s. Our measurements indicate that an oven volume 1000 times smaller could still hold enough source metal for decades of continuous operation
Simulation-based design of pragmatic trials in psoriatic arthritis using propensity scores
No full textDesign of clinical trials requires careful decision-making across several dimensions, including endpoints, eligibility criteria, and subgroup enrichment. Clinical trial simulation can be an informative tool in trial design, providing empirical evidence by which to evaluate and compare the results of hypothetical trials with varying designs. In this paper, we introduce a novel simulation-based approach using observational data to inform the design of a future pragmatic trial. To account for likely confounding by indication, we utilize propensity score-adjusted models to simulate hypothetical trials under alternative endpoints and enrollment criteria. We apply our approach to the design of pragmatic trials in psoriatic arthritis, using observational data embedded within the Tight Control of Inflammation in Early Psoriatic Arthritis study to simulate hypothetical open-label trials comparing treatment with tumor necrosis factor-α inhibitors to methotrexate. We first validate our simulations of a trial with traditional enrollment criteria and endpoints against a recently published trial. Next, we compare simulated treatment effects in patient populations defined by traditional and broadened enrollment criteria, where the latter is consistent with a future pragmatic trial. In each trial, we also consider five candidate primary endpoints. Our results highlight how changes in the enrolled population and primary endpoints may qualitatively alter study findings and the ability to detect heterogeneous treatment effects between clinical subgroups. These considerations, among others, are important for designing a future pragmatic trial aimed at having high external validity with relevance for real-world clinical practice. Our approach may be generalized to the study of other conditions where existing trial data are limited or do not generalize well to real-world clinical practice, but where observational data are available
Enhancing the Summative Assessment of Practical Science: A Systemic Approach. Project Calibrate Final Report
No full textProject Calibrate is a collaboration between the Department of Education at the University of Oxford and AQA Research. The project which took place from 2018-2021 aimed to design, implement and test summative assessments of practical science. This report presents the overall approach, the publications as well as engagement activities, and other outputs of the project
Employing learning health system principles to advance research on severe neonatal and paediatric illness in Kenya
No full textWe have worked to develop a Clinical Information Network (CIN) in Kenya as an early form of learning health systems (LHS) focused on paediatric and neonatal care that now spans 22 hospitals. CIN's aim was to examine important outcomes of hospitalisation at scale, identify and ultimately solve practical problems of service delivery, drive improvements in quality and test interventions. By including multiple routine settings in research, we aimed to promote generalisability of findings and demonstrate potential efficiencies derived from LHS. We illustrate the nature and range of research CIN has supported over the past 7 years as a form of LHS. Clinically, this has largely focused on common, serious paediatric illnesses such as pneumonia, malaria and diarrhoea with dehydration with recent extensions to neonatal illnesses. CIN also enables examination of the quality of care, for example that provided to children with severe malnutrition and the challenges encountered in routine settings in adopting simple technologies (pulse oximetry) and more advanced diagnostics (eg, Xpert MTB/RIF). Although regular feedback to hospitals has been associated with some improvements in quality data continue to highlight system challenges that undermine provision of basic, quality care (eg, poor access to blood glucose testing and routine microbiology). These challenges include those associated with increased mortality risk (eg, delays in blood transfusion). Using the same data the CIN platform has enabled conduct of randomised trials and supports malaria vaccine and most recently COVID-19 surveillance. Employing LHS principles has meant engaging front-line workers, clinical managers and national stakeholders throughout. Our experience suggests LHS can be developed in low and middle-income countries that efficiently enable contextually appropriate research and contribute to strengthening of health services and research systems
Core outcome set for preventive intervention trials in chronic and episodic migraine (COSMIG): an international, consensus-derived and multistakeholder initiative
No full textObjective Typically, migraine prevention trials focus on reducing migraine days. This narrow focus may not capture all that is important to people with migraine. Inconsistency in outcome selection across trials limits the potential for data pooling and evidence synthesis. In response, we describe the development of core outcome set for migraine (COSMIG).
Design A two-stage approach sought to achieve international, multistakeholder consensus on both the core domain set and core measurement set. Following construction of a comprehensive list of outcomes, expert panellists (patients, healthcare professionals and researchers) completed a three-round electronic-Delphi study to support a reduction and prioritisation of core domains and outcomes. Participants in a consensus meeting finalised the core domains and methods of assessment. All stages were overseen by an international core team, including patient research partners.
Results There was a good representation of patients (episodic migraine (n=34) and chronic migraine (n=42)) and healthcare professionals (n=33) with high response and retention rates. The initial list of domains and outcomes was reduced from >50 to 7 core domains for consideration in the consensus meeting, during which a 2-domain core outcome set was agreed.
Conclusion International and multistakeholder consensus emerged to describe a two-domain core outcome set for reporting research on preventive interventions for chronic and episodic migraine: migraine-specific pain and migraine-specific quality of life. Intensity of migraine pain assessed with an 11-point Numerical Rating Scale and the frequency as the number of headache/migraine days over a specified time period. Migraine-specific quality of life assessed using the Migraine Functional Impact Questionnaire
Parents’ concerns and beliefs about temperature measurement in children: a qualitative study
No full textBackground
Nearly 40% of parents with children aged 6 to 17 months consult a healthcare professional when their child has a high temperature. Clinical guidelines recommend temperature measurement in these children, but little is known about parents’ experiences of and beliefs about temperature measurement. This study aimed to explore parents’ concerns and beliefs about temperature measurement in children.
Methods
Semi-structured qualitative interviews were conducted from May 2017 to June 2018 with 21 parents of children aged 4 months to 5.5 years, who were purposively sampled from the METRIC study (a method comparison study comparing non-contact infrared thermometers to axillary and tympanic thermometers in acutely ill children). Data analysis followed a thematic approach.
Results
Parents described the importance of being able to detect fever, in particular high fevers, and how this then influenced their actions. The concept of “accuracy” was valued by parents but the aspects of performance which were felt to reflect accuracy varied. Parents used numerical values of temperature in four main ways: determining precision of the thermometer on repeat measures, detecting a “bad” fever, as an indication to administer antipyretics, or monitoring response to treatment. Family and social networks, the internet, and medical professionals and resources, were all key sources of advice for parents regarding fever, and guiding thermometer choice.
Conclusions
Temperature measurement in children has diagnostic value but can either empower, or cause anxiety and practical challenges for parents. This represents an opportunity for both improved communication between parents and healthcare professionals, and technological development, to support parents to manage febrile illness with greater confidence in the home
Mass spectrometry reveals potential of β-lactams as SARS-CoV-2 Mpro inhibitors.
No full textThe main viral protease (Mpro) of SARS-CoV-2 is a nucleophilic cysteine hydrolase and a current target for anti-viral chemotherapy. We describe a high-throughput solid phase extraction coupled to mass spectrometry Mpro assay. The results reveal some β-lactams, including penicillin esters, are active site reacting Mpro inhibitors, thus highlighting the potential of acylating agents for Mpro inhibition