bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomised multicentre clinical trial to evaluate voriconazole pre-emptive genotyping strategy in patients with risk of aspergillosis: vorigenipharm study protocol
Authors: Monserrat Villatoro Jaime , García García Irene , Bueno David , de la Cámara Rafael , Estébanez Miriam , López de la Guía Ana , Abad-Santos Francisco , Antón Cristina , Mejía Gina , Otero María José , Ramírez García Elena , Frías Iniesta Jesús , Carcas Antonio , Borobia Alberto M 
Published: April 2023

IntroductionInvasive aspergillosis is the most important cause of morbidity and mortality in patients with haematological diseases. At present, voriconazole is the first-line treatment for invasive fungal disease. The pharmacokinetic interindividual variability of voriconazole depends on genetic factors. CYP450 is involved in 70%–75% of total metabolism of voriconazole, mainly CYP3A4 and CYP2C19, with the remaining 25%–30% of metabolism conducted by monooxygenase flavins. CYP2C19 single nucleotide polymorphisms could explain 50%–55% of variability in voriconazole metabolism.Materials and methodsThe main objective is to compare efficiency of pre-emptive voriconazole genotyping with routine practice. The primary outcome is serum voriconazole on the fifth day within the therapeutic range. The secondary outcome is the combined variables of therapeutic failure and adverse events within 90 days of first administration, associated with voriconazole. A total of 146 patients at risk of invasive aspergillosis who will potentially receive voriconazole will be recruited, and CYP2C19 will be genotyped. If the patient ultimately receives voriconazole, they will be randomised (1:1 experimental/control). In the experimental arm, patients will receive a dose according to a pharmacogenetic algorithm, including CYP2C19 genotype and clinical and demographic information. In the control arm, patients will receive a dose according to clinical practice guidelines. In addition, a Spanish National Healthcare System (NHS) point-of-view cost-effectiveness evaluation will be performed. Direct cost calculations for each arm will be performed.ConclusionThis trial will provide information about the viability and cost-effectiveness of the implementation of a pre-emptive voriconazole genotyping strategy in the Spanish NHS.Ethics and disseminationA Spanish version of this protocol has been evaluated and approved by the La Paz University Hospital Ethics Committee and the Spanish Agency of Medicines and Medical Devices. Trial results will be submitted for publication in an open peer-reviewed medical speciality-specific publication.Trial registration numberEudra-CT: 2019-000376-41 andNCT04238884.
Cohort profile: FACE, prospective follow-up of chronic heart failure patients with sleep-disordered breathing indicated for adaptive servo ventilation
Authors: Tamisier Renaud , Damy Thibaud , Davy Jean-Marc , Verbraecken Johan A , Bailly Sébastien , Lavergne Florent , Palot Alain , Goutorbe Frédéric , Pépin Jean-Louis , d'Ortho Marie-Pia 
Published: April 2023

PurposeFACE is a prospective cohort study designed to assess the effect of adding adaptive servoventilation (ASV) to standard care on morbidity and mortality in patients with chronic heart failure (HF) with preserved (HFpEF), mid-range (HFmrEF) or reduced ejection fraction (HFrEF) who have sleep-disordered breathing (SDB) with an indication for ASV. We describe the study design, ongoing data collection and baseline participant characteristics.ParticipantsConsecutive patients with HFpEF, HFmrEF or HFrEF plus SDB with central sleep apnoea (CSA) and indication for ASV were enrolled in the study cohort between November 2009 and December 2018; the ASV group includes those treated with ASV and the control group consists of patients who refused ASV or stopped treatment early. Follow-up is based on standard clinical practice, with visits at inclusion, after 3, 12 and 24 months of follow-up. Primary endpoint is the time to first event: all-cause death or unplanned hospitalisation (or unplanned prolongation of a planned hospitalisation) for worsening of HF, cardiovascular death or unplanned hospitalisation for worsening of HF, and all-cause death or all-cause unplanned hospitalisation.Findings to date503 patients have been enrolled, mean age of 72 years, 88% male, 31% with HFrEF. HF was commonly of ischaemic origin, and the number of comorbidities was high. SDB was severe (median Apnoea–Hypopnoea Index 42/hour), and CSA was the main indication for ASV (69%). HF was highly symptomatic; most patients were in NYHA class II (38%) or III (29%).Future plansPatient follow-up is ongoing. Given the heterogeneous nature of the enrolled population, a decision was made to use latent class analysis to define homogeneous patient subgroups, and then evaluate outcomes by cluster, and in the ASV and control groups (overall and within patient clusters). First analysis will be performed after 3 months, a second analysis at the 2-year follow-up.Trial registration numberNCT01831128.
Association between prescribed central nervous system depressant drugs, comorbidity and cognition among hospitalised older patients: a cross-sectional study
Authors: Siddiqui Tahreem Ghazal , Cheng Socheat , Gossop Michael , Kristoffersen Espen Saxhaug , Grambaite Ramune , Lundqvist Christofer 
Published: April 2023

ObjectivesCentral nervous system depressants (CNSDs) such as opioids, benzodiazepine and Z-hypnotics are commonly used. However, CNSDs may influence cognitive function, especially in older hospitalised patients with comorbidities. The aim was to examine the association between CNSD use and cognitive function in older patients. We assessed global and domain specific cognitive function, among hospitalised older patients, including covariates for comorbidity, anxiety and depression.DesignCross-sectional hospital-based study.SettingsData was collected consecutively from inpatients at somatic wards of a general university hospital.ParticipantsOlder patients between 65 and 90 years with/without CNSD use for ≥4 weeks.Outcome measuresThe main outcome was cognitive function assessed by Cognistat. Secondary outcomes were routine clinical tests in the wards (mini-mental state examination (MMSE), trail making test (TMT) A and B, and clock drawing tests). Analyses were bivariate and multiple linear regression, adjusted for age, gender, and education. Covariates were comorbidity, depression and anxiety scores.ResultsThe main result indicated that CNSD users (n=100) had (β=–3.4, 95% CI 6.27 to –0.58, p=0.017) lower Cognistat score than non-users (n=146), adjusted for age, gender, education, anxiety and depression, but not significant when including covariate for comorbidity (β= –2.50 - 5.45; –0.46, p=0.097). Comorbidity was associated with cognitive function (β=−0.77, 95% CI −1.22 to −0.14, p=0.014). Cognistat subdimensions associated with CNSD use were language (p=0.017) and calculation (p=0.003). In clock drawing test, users had lower scores than non-users (β=−0.80, 95% CI 1.24 to −0.36, p=0.004), but no significant difference was found with MMSE and TMT A or B. Z-hypnotics were associated with reduced cognitive function.ConclusionAmong older hospitalised patients, global cognition and specific cognitive functions were associated with long-term use of CNSD medication as well as with somatic comorbidity.Trial registration numberNCT0316208122 May 2017.
Adolescent transition to adult care for HIV-infected adolescents in Kenya (ATTACH): study protocol for a hybrid effectiveness-implementation cluster randomised trial
Authors: Njuguna Irene N , Beima-Sofie Kristin , Mburu Caren W , Mugo Cyrus , Neary Jillian , Itindi Janet , Onyango Alvin , Richardson Barbra A , Rubin Means Arianna , Sharma Monisha , Weiner Bryan J , Wagner Anjuli D , Oyiengo Laura , Wamalwa Dalton , John-Stewart Grace 
Published: April 2023

IntroductionSuccessfully transitioning adolescents to adult HIV care is critical for optimising outcomes. Disclosure of HIV status, a prerequisite to transition, remains suboptimal in sub-Saharan Africa. Few interventions have addressed both disclosure and transition. An adolescent transition package (ATP) that combines disclosure and transition tools could support transition and improve outcomes.Methods and analysisIn this hybrid type 1 effectiveness-implementation cluster randomised controlled trial, 10 HIV clinics with an estimated ≥100 adolescents and young adults age 10–24 living with HIV (ALWHIV) in Kenya will be randomised to implement the ATP and compared with 10 clinics receiving standard of care. The ATP includes provider tools to assist disclosure and transition. Healthcare providers at intervention clinics will receive training on ATP use and support to adapt it through continuous quality improvement cycles over the initial 6 months of the study, with continued implementation for 1 year. The primary outcome is transition readiness among ALWHIV ages 15–24 years, assessed 6 monthly using a 22-item readiness score. Secondary outcomes including retention and viral suppression among ALWHIV at the end of the intervention period (month 18), implementation outcomes (acceptability, feasibility, fidelity, coverage and penetration) and programme costs complement effectiveness outcomes. The primary analysis will be intent to treat, using mixed-effects linear regression models to compare transition readiness scores (overall and by domain (HIV literacy, self-management, communication, support)) over time in control and intervention sites with adjustment for multiple testing, accounting for clustering by clinic and repeated assessments. We will estimate the coefficients and 95% CIs with a two- sided α=0.05.Ethics and disseminationThe study was approved by the University of Washington Institutional Review Board and the Kenyatta National Hospital Ethics and Research Committee. Study results will be shared with participating facilities, county and national policy-makers.Trials registration numberNCT03574129.
Rotator cuff-related shoulder pain: does the type of exercise influence the outcomes? Protocol of a randomised controlled trial
Authors: Dubé Marc-Olivier , Desmeules François , Lewis Jeremy , Roy Jean-Sébastien 
Published: April 2023

IntroductionLifetime prevalence of shoulder pain is 70%, and approximately 50% of people with shoulder pain will experience pain for more than a year. Rotator cuff-related shoulder pain (RCRSP) is the most common shoulder condition and the main non-surgical intervention is exercise therapy. For approximately 30% of people with RCRSP, this approach does not lead to a significant reduction in symptoms. This may be due to an inappropriate dosage or choice of exercises. The aim of this investigation is to compare the short, mid and long-term effects, in terms of symptoms, functional limitations, kinesiophobia and pain catastrophising, of three different shoulder rehabilitation approaches (education, strengthening, motor control) in adults with RCRSP.Methods and analysisIn this single-blind (assessor), parallel-group, randomised clinical trial, 123 adults presenting with RCRSP will take part in a 12-week rehabilitation programme. They will be randomly assigned to one of three groups (education only, strengthening approach or motor control-focused approach). Abbreviated version of the Disabilities of the Arm, Shoulder and Hand Questionnaire, the primary outcome, Western Ontario Rotator Cuff Index and Brief Pain Inventory will evaluate symptoms and functional limitations, while Tampa Scale of Kinesiophobia and Pain Catastrophizing Scale will evaluate pain-related fear and catastrophising at baseline and at 3, 6, 12 and 24 weeks. Ultrasonographic acromiohumeral distances and tendon thickness will be assessed at baseline and 12 weeks. Intervention groups will be compared on outcomes with intention-to-treat analyses using two-way repeated measures analysis of variance if the data are normally distributed or non-parametric analysis of longitudinal data if they are not.Ethics and disseminationEthics approval was obtained from the Sectorial Rehabilitation and Social Integration Research Ethics Committee of the Centre Intégré Universitaire de Santé et de Services Sociaux de la Capitale Nationale (CIUSSS-CN). Results will be disseminated through international publications in peer-reviewed journals, in addition to international conference presentations.Trial registration numberNCT03892603.
A study protocol for a multicentre, prospective, before-and-after trial evaluating the feasibility of implementing targeted SEDation after initiation of mechanical ventilation in the emergency department (The ED-SED Pilot Trial)
Authors: Fuller Brian M , Roberts Brian W , Mohr Nicholas M , Pappal Ryan D , Stephens Robert J , Yan Yan , Carpenter Chris , Kollef Marin H , Avidan Michael Simon 
Published: April 2023

IntroductionSedation is a cornerstone therapy in the management of patients receiving mechanical ventilation and is highly influential on outcome. Early sedation depth appears especially influential, as early deep sedation is associated with worse outcome when compared with light sedation. Our research group has shown that patients receiving mechanical ventilation in the emergency department (ED) are exposed to deep sedation commonly, and ED sedation depth is impactful on intensive care unit (ICU) care and clinical outcomes. While extensive investigation has occurred for patients in the ICU, comparatively little data exist from the ED. Given the influence that ED sedation seems to carry, as well as a lack of ED-based sedation trials, there is significant rationale to investigate ED-based sedation as a means to improve outcome.Methods and analysisThis is a multicentre (n=3) prospective, before-and-after pilot trial examining the feasibility of implementing targeted sedation in the immediate postintubation period in the ED. A cohort of 344 patients receiving mechanical ventilation in ED will be included. Feasibility outcomes include: (1) participant recruitment; (2) proportion of Richmond Agitation-Sedation Scale (RASS) scores in the deep sedation range; (3) reliability (agreement) of RASS measurements performed by bedside ED nurses; and (4) adverse events. The proportion of deep sedation measurements before and after the intervention will be compared using the χ2test. Logistic regression will be used to compare before-and-after differences, adjusting for potential confounders. The inter-rater correlation coefficient will be used to assess paired observations between a study team member and bedside ED nurses, and to describe reliability of RASS measurements.Ethics and disseminationThe Human Research Protection Office at Washington University in St. Louis School of Medicine has approved the study. The publication of peer-reviewed manuscripts and the presentation of abstracts at scientific meetings will be used to disseminate the work.RegistrationClinicalTrials.gov identifierNCT04410783.
Bilateral Remote Ischaemic Conditioning in Children (BRICC) trial: protocol for a two-centre, double-blind, randomised controlled trial in young children undergoing cardiac surgery
Authors: Drury Nigel E , Bi Rehana , Woolley Rebecca L , Stickley John , Morris Kevin P , Montgomerie James , van Doorn Carin , Dunn Warwick B , Madhani Melanie , Ives Natalie J , Kirchhof Paulus , Jones Timothy J 
Published: April 2023

IntroductionMyocardial protection against ischaemic-reperfusion injury is a key determinant of heart function and outcome following cardiac surgery in children. However, with current strategies, myocardial injury occurs routinely following aortic cross-clamping, as demonstrated by the ubiquitous rise in circulating troponin. Remote ischaemic preconditioning, the application of brief, non-lethal cycles of ischaemia and reperfusion to a distant organ or tissue, is a simple, low-risk and readily available technique which may improve myocardial protection. The Bilateral Remote Ischaemic Conditioning in Children (BRICC) trial will assess whether remote ischaemic preconditioning, applied to both lower limbs immediately prior to surgery, reduces myocardial injury in cyanotic and acyanotic young children.Methods and analysisThe BRICC trial is a two-centre, double-blind, randomised controlled trial recruiting up to 120 young children (age 3 months to 3 years) undergoing primary repair of tetralogy of Fallot or surgical closure of an isolated ventricular septal defect. Participants will be randomised in a 1:1 ratio to either bilateral remote ischaemic preconditioning (3×5 min cycles) or sham immediately prior to surgery, with follow-up until discharge from hospital or 30 days, whichever is sooner. The primary outcome is reduction in area under the time-concentration curve for high-sensitivity (hs) troponin-T release in the first 24 hours after aortic cross-clamp release. Secondary outcome measures include peak hs-troponin-T, vasoactive inotrope score, arterial lactate and central venous oxygen saturations in the first 12 hours, and lengths of stay in the paediatric intensive care unit and the hospital.Ethics and disseminationThe trial was approved by the West Midlands-Solihull National Health Service Research Ethics Committee (16/WM/0309) on 5 August 2016. Findings will be disseminated to the academic community through peer-reviewed publications and presentation at national and international meetings. Parents will be informed of the results through a newsletter in conjunction with a local charity.Trial registration numberNCT12923441.
COVID-19 pandemic: a qualitative study with an opportunity-centric approach from an ICU perspective in a teaching hospital. Upsides worth to secure?
Authors: Klein Dorthe O , Moelans Bodine , Savelberg Wilma , van der Horst Iwan C C , Van Mook Walther N K A , Rennenberg Roger J M W 
Published: April 2023

ObjectivesDuring the COVID-19 pandemic, the staff in the intensive care unit (ICU) was materially, physically and emotionally challenged. This qualitative study investigated the effects that ICU staff experienced and were considered of value to be permanently implemented.SettingICU in an university medical centre during the first wave of the COVID-19 pandemic.DesignAn opportunity-centric approach was applied in individual semi-structured interviews to optimise the achieved results and was guided by the theoretical model of appreciative inquiry (AI).ParticipantsFifteen ICU staff members (8 nurses and 7 intensivists) participated.ResultsWorking during the COVID-19 pandemic catalysed interprofessional collaboration and team learning in the ICU on an individual and team level, centred around a common goal: taking care of critically ill patients with COVID-19. The effect of interprofessional collaboration was that provisions were taken care of quicker than usual, without bureaucratic delays. However, this effect was experienced to be transient. Also, ICU staff perceived limited possibilities to help patients and families around the palliative phase, and they perceived a lack of appreciation from higher management. This is a point of future attention: how to make this perceived lack of appreciation more visible to all (ICU) staff.ConclusionRegarding our primary question, the ICU staff voiced that the direct communication and collaboration are the most important elements of the COVID-19 peak they would like to preserve. Furthermore, it was learnt that consolation and support for family members should not be forgotten. Considering the results, we believe that further research concerning team reflexivity might contribute to (or enhance) our knowledge about working together during and after a crisis.
Multicentre study protocol comparing standard NRP to deveLoped Educational Modules for Resuscitation of Neonates in the Delivery Room with Congenital Heart Disease (LEARN-CHD)
Authors: Levy Philip , Thomas Alyssa R , Law Brenda Hiu Yan , Joynt Chloe , Gupta Ruby , Elshenawy Summer , Reed Danielle , Pavlek Leeann R , Shepherd Jennifer , Gowda Sharada , Johnson Beth Ann , Ball Molly , Ali Noorjahan 
Published: April 2023

IntroductionInfants born with critical congenital heart defects (CCHDs) have unique transitional pathophysiology that often requires special resuscitation and management considerations in the delivery room (DR). While much is known about neonatal resuscitation of infants with CCHDs, current neonatal resuscitation guidelines such as the neonatal resuscitation programme (NRP) do not include algorithm modifications or education specific to CCHDs. The implementation of CCHD specific neonatal resuscitation education is further hampered by the large number of healthcare providers (HCPs) that need to be reached. Online learning modules (eLearning) may provide a solution but have not been designed or tested for this specific learning need. Our objective in this study is to design targeted eLearning modules for DR resuscitation of infants with specific CCHDs and compare HCP knowledge and team performance in simulated resuscitations among HCPs exposed to these modules compared with directed CCHD readings.Methods and analysisIn a prospective multicentre trial, HCP proficient in standard NRP education curriculum are randomised to either (a) directed CCHD readings or (b) CCHD eLearning modules developed by the study team. The efficacy of these modules will be evaluated using (a) individual preknowledge/postknowledge testing and (b) team-based resuscitation simulations.Ethics and disseminationThis study protocol is approved by nine participating sites: the Boston Children’s Hospital Institutional Review Board (IRB-P00042003), University of Alberta Research Ethics Board (Pro00114424), the Children’s Wisconsin IRB (1760009-1), Nationwide Children’s Hospital IRB (STUDY00001518), Milwaukee Children’s IRB (1760009-1) and University of Texas Southwestern IRB (STU-2021-0457) and is under review at following sites: University of Cincinnati, Children’s Healthcare of Atlanta, Children’s Hospital of Los Angeles and Children’s Mercy-Kansas City. Study results will be disseminated to participating individuals in a lay format and presented to the scientific community at paediatric and critical care conferences and published in relevant peer-reviewed journals.