Search

Abstract Background Graft rejection and chronic CNI toxicity remain obstacles to organ transplant success. Current formulations of tacrolimus, such as Prograf® and Advagraf™, exhibit limitations in terms of pharmacokinetics and tolerability, related in part to suboptimal bioavailability. As dosing non-compliance can result in graft rejection, the once daily formulation of tacrolimus, Advagraf™, was developed (vs 2x/day Prograf®). Benefits of Advagraf™ are counterbalanced by delayed achievement of therapeutic trough levels and need for up to 50% higher doses to maintain Prograf®-equivalent troughs. Envarsus® is also a prolonged-release once-daily tacrolimus formulation, developed using MeltDose™ drug-delivery technology to increase drug bioavailability; improved bioavailability results in low patient drug absorption variability and less pronounced peak-to-trough fluctuations. In phase III de novo kidney transplant studies, Envarsus® proved non-inferior to twice-daily tacrolimus; however, no phase IV studies show superiority of Envarsus® vs Advagraf™ in de novo liver transplant (LTx) recipients. Methods The EnGraft compares bioavailability and tests superiority of Envarsus® (test arm) versus Advagraf™ (comparator arm) in de novo LTx recipients. A total of 268 patients from 15 German transplant centres will be randomised 1:1 within 14 days post-LTx. The primary endpoint is dose-normalised trough level (C/D ratio) measured 12 weeks after randomisation. Secondary endpoints include the number of dose adjustments, time to reach first defined trough level and incidence of graft rejections. Additionally, clinical and laboratory parameters will be assessed over a 3-year period. Discussion C/D ratio is an estimate for tacrolimus bioavailability. Improving bioavailability and increasing C/D ratio using Envarsus could reduce renal dysfunction and other tacrolimus-related toxicities; previous trials have shown that a higher C/D ratio (i.e. slower tacrolimus metabolism) is not only associated with improved renal function but also linked to reduced neurotoxic side effects. A higher C/D ratio could improve clinical outcomes for LTx recipients; EnGraft has begun, with one third of patients recruited by January 2022. Trial registration This trial has been registered (4 May 2020) in the EU Clinical Trials Register, EudraCT-Nummer: 2020–000796-20. Additionally, this trial has been registered (22 January 2021) at ClinicalTrials.gov: NCT04720326. The trial received a favourable opinion from the concerned lead ethics committee at the University of Regensburg, under the reference 20–1842-112.

Abstract Background Anaemia in pregnancy remains prevalent in Nepal and causes severe adverse health outcomes. Methods This non-blinded cluster-randomised controlled trial in the plains of Nepal has two study arms: (1) Control: routine antenatal care (ANC); (2) Home visiting, iron supplementation, Participatory Learning and Action (PLA) groups, plus routine ANC. Participants, including women in 54 non-contiguous clusters (mean 2582; range 1299–4865 population) in Southern Kapilbastu district, are eligible if they consent to menstrual monitoring, are resident, married, aged 13–49 years and able to respond to questions. After 1–2 missed menses and a positive pregnancy test, consenting women

Abstract Background This case study’s novelty lies in the potential to link a new sign in pulmonary embolism diagnosis which does not increase cost but could lead to more rapid treatment. Early intervention in these cases is vital to decrease morbidity and mortality. Case presentation An otherwise healthy 20-year-old female patient presents to the emergency department for evaluation of a syncopal episode which occurred just prior to arriving to the emergency department. Patient also complains of ongoing shortness of breath while performing activities of daily living for 3 weeks. In this patient with no known valvular disease, physical exam revealed a systolic murmur heard only posteriorly. Subsequent emergency department workup revealed bilateral massive pulmonary emboli. Implications A new flow murmur heard in atypical locations could be an early sign to aid in the detection and diagnosis of pulmonary embolism. This is especially important in rural community hospitals with limited access to advanced imaging modalities.

The increasing availability and capabilities of mobile phones make them a feasible means of data collection. Electronic Data Capture (EDC) systems have been used widely for public health monitoring and surveillance activities, but documentation of their use in complicated research studies requiring multiple systems is limited. This paper shares our experiences of designing and implementing a complex multi-component EDC system for a community-based four-armed cluster-Randomised Controlled Trial in the rural plains of Nepal, to help other researchers planning to use EDC for complex studies in low-income settings. We designed and implemented three interrelated mobile phone data collection systems to enrol and follow-up pregnant women (trial participants), and to support the implementation of trial interventions (women’s groups, food and cash transfers). 720 field staff used basic phones to send simple coded text messages, 539 women’s group facilitators used Android smartphones with Open Data Kit Collect, and 112 Interviewers, Coordinators and Supervisors used smartphones with CommCare. Barcoded photo ID cards encoded with participant information were generated for each enrolled woman. Automated systems were developed to download, recode and merge data for nearly real-time access by researchers. The systems were successfully rolled out and used by 1371 staff. A total of 25,089 pregnant women were enrolled, and 17,839 follow-up forms completed. Women’s group facilitators recorded 5717 women’s groups and the distribution of 14,647 food and 13,482 cash transfers. Using EDC sped up data collection and processing, although time needed for programming and set-up delayed the study inception. EDC using three interlinked mobile data management systems (FrontlineSMS, ODK and CommCare) was a feasible and effective method of data capture in a complex large-scale trial in the plains of Nepal. Despite challenges including prolonged set-up times, the systems met multiple data collection needs for users with varying levels of literacy and experience.

Evidence supports direct referral for imaging by physical therapists. Accuracy and self-efficacy for imaging decisions have not been investigated in entry-level doctor of physical therapy (DPT) students. The purpose of this study was to understand the relationship between entry-level DPT instruction and accuracy and self-efficacy for imaging referral due to acute knee trauma. A second purpose was to identify relationships between accuracy and self-efficacy. An online survey was sent via e-mail to program directors in accredited DPT programs in the United States with an invitation to forward the survey to DPT students. The survey captured demographic information and included five questions that assessed the respondent's ability to apply the Ottawa Knee Rules (OKR). Self-efficacy was assessed using the Physiotherapist Student Self-Efficacy (PSE) questionnaire, a self-rated 5-point Likert scaled tool. Of 240 surveys, DPT students who completed imaging coursework had greater accuracy and higher self-efficacy (68.0% correct (95% CI, 63.6–72.5), PSE = 3.67, P <.001) compared to students who had not (45.8% correct (95% CI, 40.8–50.7), PSE = 2.67, P <.001). Conclusion: Accuracy by DPT students who completed imaging coursework was significantly improved and comparable to values from autonomous providers. [ABSTRACT FROM AUTHOR]