bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal olmesartan exposure causing neonatal failure
Authors: Pérez-Iranzo Antonio , Ferreres Ana Nos , Bou Aranzazu Jarque 
Published: December 2018

Although angiotensin II receptor blockers (ARBs) are contraindicated during pregnancy, new cases are currently being reported.A 32-week preterm neonate was admitted after C-section due to maternal oligohydramnios. He presented with Potter phenotype, pulmonary hypoplasia with pneumothorax, systemic hypotension and anuria. He required chest drain insertion and continuous positive airway pressure (CPAP), volume expansion plus inotropic support with persistent renal failure. Mother confirmed olmesartan intake during entire pregnancy. Peritoneal dialysis was started with improvement in renal markers and progressive recovery of renal function. He has been followed up until the age of 2 years, observing improved renal function with a glomerular filtration rate (GFR) of 58 mL/min/1.72 m2.Both angiogenesis-converting enzyme inhibitor and ARBs affect nephrogenesis; ARBs being more harmful due to its higher activity. Although some patients may recover normal renal function, its teratogen effect may have fatal consequences. Thus, it is important to emphasise its harmful effects in neonates to avoid new cases.
Point-of-care washing of allogeneic red blood cells for the prevention of transfusion-related respiratory complications (WAR-PRC): a protocol for a multicenter randomised clinical trial in patients undergoing cardiac surgery
Authors: Warner Matthew A , Welsby Ian J , Norris Phillip J , Silliman Christopher C , Armour Sarah , Wittwer Erica D , Santrach Paula J , Meade Laurie A , Liedl Lavonne M , Nieuwenkamp Chelsea M , Douthit Brian , van Buskirk Camille M , Schulte Phillip J , Carter Rickey E , Kor Daryl J 
Published: December 2018

IntroductionThe transfusion-related respiratory complications, transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO), are leading causes of transfusion-related morbidity and mortality. At present, there are no effective preventive strategies with red blood cell (RBC) transfusion. Although mechanisms remain incompletely defined, soluble biological response modifiers (BRMs) within the RBC storage solution may play an important role. Point-of-care (POC) washing of allogeneic RBCs may remove these BRMs, thereby mitigating their impact on post-transfusion respiratory complications.Methods and analysisThis is a multicenter randomised clinical trial of standard allogeneic versus washed allogeneic RBC transfusion for adult patients undergoing cardiac surgery testing the hypothesis that POC RBC washing is feasible, safe, and efficacious and will reduce recipient immune and physiologic responses associated with transfusion-related respiratory complications. Relevant clinical outcomes will also be assessed. This investigation will enrol 170 patients at two hospitals in the USA. Simon’s two-stage design will be used to assess the feasibility of POC RBC washing. The primary safety outcomes will be assessed using Wilcoxon Rank-Sum tests for continuous variables and Pearson chi-square test for categorical variables. Standard mixed modelling practices will be employed to test for changes in biomarkers of lung injury following transfusion. Linear regression will assess relationships between randomised group and post-transfusion physiologic measures.Ethics and disseminationSafety oversight will be conducted under the direction of an independent Data and Safety Monitoring Board (DSMB). Approval of the protocol was obtained by the DSMB as well as the institutional review boards at each institution prior to enrolling the first study participant. This study aims to provide important information regarding the feasibility of POC washing of allogeneic RBCs and its potential impact on ameliorating post-transfusion respiratory complications. Additionally, it will inform the feasibility and scientific merit of pursuing a more definitive phase II/III clinical trial.RegistrationClinicalTrials.gov registration number isNCT02094118(Pre-results).
Radical cystectomy (bladder removal) against intravesical BCG immunotherapy for high-risk non-muscle invasive bladder cancer (BRAVO): a protocol for a randomised controlled feasibility study
Authors: Oughton Jamie B , Poad Heather , Twiddy Maureen , Collinson Michelle , Hiley Victoria , Gordon Kathryn , Johnson Mark , Jain Sunjay , Noon Aidan P , Chahal Rohit , Simms Matt , Dooldeniya Mohantha , Koenig Phillip , Goodwin Louise , Brown Julia M , Catto James W F 
Published: December 2018

IntroductionHigh-risk non-muscle invasive bladder cancer (HRNMIBC) is a heterogeneous disease that can be difficult to predict. While around 25% of cancers progress to invasion and metastases, the remaining majority of tumours remain within the bladder. It is uncertain whether patients with HRNMIBC are better treated with intravesical maintenance BCG (mBCG) immunotherapy or primary radical cystectomy (RC). A definitive randomised controlled trial (RCT) is needed to compare these two different treatments but may be difficult to recruit to and has not been attempted to date. Before undertaking such an RCT, it is important to understand whether such a comparison is possible and how best to achieve it.Methods and analysisBRAVO is a multi-centre, parallel-group, mixed-methods, individually randomised, controlled, feasibility study for patients with HRNMIBC. Participants will be randomised to receive either mBCG immunotherapy or RC. The primary objective is to assess the feasibility and acceptability of performing the definitive phase III trial via estimation of eligibility and recruitment rates, assessing uptake of allocated treatment and compliance with mBCG, determining quality-of-life questionnaire completion rates and exploring reasons expressed by patients for declining recruitment into the study. We aim to recruit 60 participants from six centres in the UK. Surgical trials with disparate treatment options find recruitment challenging from both the patient and clinician perspective. By building on the experiences of other similar trials through implementing a comprehensive training package aimed at clinicians to address these challenges (qualitative substudy), we hope that we can demonstrate that a phase III trial is feasible.Ethics and disseminationThe study has ethical approval (16/YH/0268). Findings will be made available to patients, clinicians, the funders and the National Health Service through traditional publishing and social media.Trial registration numberISRCTN12509361; Pre results.
Evaluation of a complex intervention (Engager) for prisoners with common mental health problems, near to and after release: study protocol for a randomised controlled trial
Authors: Kirkpatrick Tim , Lennox Charlotte , Taylor Rod , Anderson Rob , Maguire Michael , Haddad Mark , Michie Susan , Owens Christabel , Durcan Graham , Stirzaker Alex , Henley William , Stevenson Caroline , Carroll Lauren , Quinn Cath , Brand Sarah Louise , Harris Tirril , Stewart Amy , Todd Roxanne , Rybczynska-Bunt Sarah , Greer Rebecca , Pearson Mark , Shaw Jenny , Byng Richard 
Published: December 2018

IntroductionThe ‘Engager’ programme is a ‘through-the-gate’ intervention designed to support prisoners with common mental health problems as they transition from prison back into the community. The trial will evaluate the clinical and cost-effectiveness of the Engager intervention.Methods and analysisThe study is a parallel two-group randomised controlled trial with 1:1 individual allocation to either: (a) the Engager intervention plus standard care (intervention group) or (b) standard care alone (control group) across two investigation centres (South West and North West of England). Two hundred and eighty prisoners meeting eligibility criteria will take part. Engager is a person-centred complex intervention delivered by practitioners and aimed at addressing offenders’ mental health and social care needs. It comprises one-to-one support for participants prior to release from prison and for up to 20 weeks postrelease. The primary outcome is change in psychological distress measured by the Clinical Outcomes in Routine Evaluation-Outcome Measure at 6 months postrelease. Secondary outcomes include: assessment of subjective met/unmet need, drug and alcohol use, health-related quality of life and well-being-related quality of life measured at 3, 6 and 12 months postrelease; change in objective social domains, drug and alcohol dependence, service utilisation and perceived helpfulness of services and change in psychological constructs related to desistence at 6 and 12 months postrelease; and recidivism at 12 months postrelease. A process evaluation will assess fidelity of intervention delivery, test hypothesised mechanisms of action and look for unintended consequences. An economic evaluation will estimate the cost-effectiveness.Ethics and disseminationThis study has been approved by the Wales Research Ethics Committee 3 (ref: 15/WA/0314) and the National Offender Management Service (ref: 2015–283). Findings will be disseminated to commissioners, clinicians and service users via papers and presentations.Trial registration numberISRCTN11707331; Pre-results.
Cost-effectiveness of a community-delivered multicomponent intervention compared with enhanced standard care of obese adolescents: cost-utility analysis alongside a randomised controlled trial (the HELP trial)
Authors: Panca Monica , Christie Deborah , Cole Tim J , Costa Silvia , Gregson John , Holt Rebecca , Hudson Lee D , Kessel Anthony S , Kinra Sanjay , Mathiot Anne , Nazareth Irwin , Wataranan Jay , Wong Ian Chi Kei , Viner Russell M , Morris Stephen 
Published: December 2018

ObjectiveTo undertake a cost-utility analysis of a motivational multicomponent lifestyle-modification intervention in a community setting (the Healthy Eating Lifestyle Programme (HELP)) compared with enhanced standard care.DesignCost-utility analysis alongside a randomised controlled trial.SettingCommunity settings in Greater London, England.Participants174 young people with obesity aged 12–19 years.InterventionsIntervention participants received 12 one-to-one sessions across 6 months, addressing lifestyle behaviours and focusing on motivation to change and self-esteem rather than weight change, delivered by trained graduate health workers in community settings. Control participants received a single 1-hour one-to-one nurse-delivered session providing didactic weight-management advice.Main outcome measuresMean costs and quality-adjusted life years (QALYs) per participant over a 1-year period using resource use data and utility values collected during the trial. Incremental cost-effectiveness ratio (ICER) was calculated and non-parametric bootstrapping was conducted to generate a cost-effectiveness acceptability curve (CEAC).ResultsMean intervention costs per participant were £918 for HELP and £68 for enhanced standard care. There were no significant differences between the two groups in mean resource use per participant for any type of healthcare contact. Adjusted costs were significantly higher in the intervention group (mean incremental costs for HELP vs enhanced standard care £1003 (95% CI £837 to £1168)). There were no differences in adjusted QALYs between groups (mean QALYs gained 0.008 (95% CI −0.031 to 0.046)). The ICER of the HELP versus enhanced standard care was £120 630 per QALY gained. The CEAC shows that the probability that HELP was cost-effective relative to the enhanced standard care was 0.002 or 0.046, at a threshold of £20 000 or £30 000 per QALY gained.ConclusionsWe did not find evidence that HELP was more effective than a single educational session in improving quality of life in a sample of adolescents with obesity. HELP was associated with higher costs, mainly due to the extra costs of delivering the intervention and therefore is not cost-effective.Trial registration numberISRCTN99840111.
Antiretroviral therapy for pregnant women living with HIV or hepatitis B: a systematic review and meta-analysis
Authors: Siemieniuk Reed A , Foroutan Farid , Mirza Reza , Mah Ming Jinell , Alexander Paul E , Agarwal Arnav , Lesi Olufunmilayo , Merglen Arnaud , Chang Yaping , Zhang Yuan , Mir Hassan , Hepworth Elliot , Lee Yung , Zeraatkar Dena , Guyatt Gordon H 
Published: December 2018

ObjectiveTo assess the impact of various antiretroviral/antiviral regimens in pregnant women living with HIV or hepatitis B virus (HBV).DesignWe performed random effects meta-analysis for HIV-related outcomes and network meta-analysis for HBV outcomes, and used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to assess quality separately for each outcome.Data sourcesEmbase and Medline to February 2017.Eligibility criteriaFor maternal outcomes, we considered randomised controlled trials (RCTs) comparing tenofovir-based regimens with those with alternative nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). For child outcomes, we included RCTs and comparative observational studies of tenofovir-based regimens versus alternative NRTIs regimens or, for HBV, placebo.ResultsTen studies (seven RCTs) met the inclusion criteria for maternal and child outcomes, and an additional 33 studies (12 RCTs) met the inclusion criteria for HBV-specific outcomes. The most common comparison was tenofovir and emtricitabine versus zidovudine and lamivudine. There was no apparent difference between tenofovir-based regimens and alternatives in maternal outcomes, including serious laboratory adverse events (low certainty) and serious clinical adverse events (moderate certainty). There was no difference between NRTIs in vertical transmission of HIV: 1 more per 1000, 8 fewer to 10 more, low certainty; or vertical transmission of HBV: 7 fewer per 1000, 10 fewer to 38 more, moderate certainty. We found moderate certainty evidence that tenofovir/emtricitabine increases the risk of stillbirths and early neonatal mortality (51 more per 1000, 11 more to 150 more) and the risk of early premature delivery at <34 weeks (42 more per 1000, 2 more to 127 more).ConclusionsTenofovir/emtricitabine is likely to increase stillbirth/early neonatal death and early premature delivery compared with zidovudine/lamivudine, but certainty is low when they are not coprescribed with lopinavir/ritonavir. Other outcomes are likely similar between antiretrovirals.PROSPERO registration numberCRD42017054392.
Contractility surrogates derived from three-dimensional lead motion analysis and prediction of acute haemodynamic response to CRT
Authors: Ross Stian , Odland Hans Henrik , Fischer Trent , Edvardsen Thor , Gammelsrud Lars Ove , Haland Trine Fink , Cornelussen Richard , Hopp Einar , Kongsgaard Erik 
Published: December 2018

BackgroundPatient-specific left ventricular (LV) lead optimisation strategies with immediate feedback on cardiac resynchronisation therapy (CRT) effectiveness are needed. The purpose of this study was to compare contractility surrogates derived from biventricular lead motion analysis to the peak positive time derivative of LV pressure (dP/dtmax)in patients undergoing CRT implantation.MethodsTwenty-seven patients underwent CRT implantation with continuous haemodynamic monitoring. The right ventricular (RV) lead was placed in apex and a quadripolar LV lead was placed laterally. Biplane fluoroscopy cine films facilitated construction of three-dimensional RV–LV interlead distance waveforms at baseline and under biventricular pacing (BIVP) from which the following contractility surrogates were derived; fractional shortening (FS), time to peak systolic contraction and peak shortening of the interlead distance (negative slope). Acute haemodynamic CRT response was defined as LV ∆dP/dtmax≥ 10 %.ResultsWe observed a mean increase in dP/dtmaxunder BIVP (899±205 mm Hg/s vs 777±180 mm Hg/s, p<0.001). Based on ΔdP/dtmax, 18 patients were classified as acute CRT responders and nine as non-responders (23.3%±10.6% vs 1.9±5.3%, p<0.001). The baseline RV–LV interlead distance was associated with echocardiographic LV dimensions (end diastole: R=0.61, p=0.001 and end systole: R=0.54, p=0.004). However, none of the contractility surrogates could discriminate between the acute CRT responders and non-responders (ΔFS: −2.5±2.6% vs − 2.0±3.1%, p=0.50; Δtime to peak systolic contraction: −9.7±18.1% vs −10.8±15.1%, p=0.43 and Δpeak negative slope: −8.7±45.9% vs 12.5±54.8 %, p=0.09).ConclusionThe baseline RV–LV interlead distance was associated with echocardiographic LV dimensions. In CRT recipients, contractility surrogates derived from the RV–LV interlead distance waveform could not discriminate between acute haemodynamic responders and non-responders.
Autocrine TGFβ Is a Survival Factor for Monocytes and Drives Immunosuppressive Lineage Commitment
Authors: Gonzalez-Junca Alba , Driscoll Kyla E. , Pellicciotta Ilenia , Du Shisuo , Lo Chen Hao , Roy Ritu , Parry Renate , Tenvooren Iliana , Marquez Diana M. , Spitzer Matthew H. , Barcellos-Hoff Mary Helen 
Published: December 2018

Abstract
Transforming growth factor β (TGFβ) is an effector of immune suppression and contributes to a permissive tumor microenvironment that compromises effective immunotherapy. We identified a correlation between TGFB1 and genes expressed by myeloid cells, but not granulocytes, in The Cancer Genome Atlas lung adenocarcinoma data, in which high TGFB1 expression was associated with poor survival. To determine whether TGFβ affected cell fate decisions and lineage commitment, we studied primary cultures of CD14+ monocytes isolated from peripheral blood of healthy donors. We discovered that TGFβ was a survival factor for CD14+ monocytes, which rapidly executed an apoptotic program in its absence. Continued exposure to TGFβ in combination with granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 6 (IL6) amplified HLA-DRlowCD14+CD11b+CD33+ myeloid-derived suppressor cells (MDSCs) at the expense of macrophage and dendritic cell (DC) differentiation. MDSCs generated in the presence of TGFβ were more effective in suppressing T-cell proliferation and promoted the T regulatory cell phenotype. In contrast, inhibition of TGFβ signaling using a small-molecule inhibitor of receptor kinase activity in CD14+ monocytes treated with GM-CSF and IL6 decreased MDSC differentiation and increased differentiation to proinflammatory macrophages and antigen-presenting DCs. The effect of autocrine and paracrine TGFβ on myeloid cell survival and lineage commitment suggests that pharmacologic inhibition of TGFβ-dependent signaling in cancer would favor antitumor immunity.
Bivariate Genome-Wide Association Scan Identifies 6 Novel Loci Associated With Lipid Levels and Coronary Artery Disease
Authors: Siewert Katherine M. , Voight Benjamin F. 
Published: December 2018

Background:
Plasma lipid levels are heritable and genetically associated with risk of coronary artery disease (CAD). However, genome-wide association studies (GWAS) routinely analyze these traits independent of one another. Joint GWAS for two related phenotypes can lead to a higher powered analysis to detect variants contributing to both traits.

Methods:
We performed a bivariate GWAS to discover novel loci associated with both heart disease, using a CAD meta-analysis (122 733 cases and 424 528 controls), and lipid traits, using results from the Global Lipid Genetics Consortium (188 577 subjects).

Results:

We identified six previously unreported loci at genome-wide significance (
P
<5×10
−8
), three which were associated with triglycerides and CAD, two which were associated with LDL (low-density lipoprotein) cholesterol and CAD, and one associated with total cholesterol and CAD. At several of our loci, the GWAS signals jointly localize with genetic variants associated with expression level changes for more than one neighboring genes, indicating that these loci may be affecting disease risk through regulatory activity.

Conclusions:
We discovered six novel variants individually associated with both lipids and CAD.
The Relationship of Cardiometabolic Risk and Auditory Processing among African Americans: The Jackson Heart Study
Authors: Smith Erin , Bishop Charles E. , Spankovich Christopher , Su Dan , Valle Karen , Schweinfurth John 
Published: December 2018

ObjectivesThere is limited research in population‐based studies on auditory processing. The purpose of this work is to determine the prevalence of auditory processing impairment in the Jackson Heart Study cohort and to identify potential relationships with cardiometabolic risk factors.Study DesignCross‐sectional study.SettingJackson Heart Study in Jackson, Mississippi.SubjectsParticipants of an all–African American cardiovascular study cohort (n = 1314).MethodsThe Quick Speech‐in‐Noise and Dichotic Digits, Double Pairs tests were used to assess auditory processing. Logistic regression and multinomial logistic regression models were used to examine how participants’ cardiometabolic risk factors and audiologic characteristics were associated with speech perception in noise and binaural integration.ResultsQuick Speech‐in‐Noise and Dichotic Digits, Double Pairs testing showed a prevalence of auditory processing impairment in 69% and 71% of the cohort, respectively, which was significantly related to age, hearing thresholds, sex, and education level. With covariate adjustment in statistical models for age, sex, pure tone average, and education level, waist circumference, systolic blood pressure, and hypertension were statistically predictive of auditory processing impairment (P <. 05).ConclusionThe results suggest a high prevalence of auditory processing deficits in the Jackson Heart Study cohort. In addition, cardiometabolic and audiologic factors show a statistically significant independent relationship with auditory impairment measures.
Riluzole for treatment of men with methamphetamine dependence: A randomized, double-blind, placebo-controlled clinical trial
Authors: Farahzadi Mohammad-Hadi , Moazen-Zadeh Ehsan , Razaghi Emran , Zarrindast Mohammad-Reza , Bidaki Reza , Akhondzadeh Shahin 
Published: December 2018

Background: Riluzole is a glutamate regulator and effective in treatment of neuropsychiatric conditions. Aims: We assessed riluzole for treatment of methamphetamine dependence. Methods: In this randomized, double-blind, placebo-controlled clinical trial, male outpatients with methamphetamine dependence who were 18–65 years old received either 50 mg riluzole ( n=34) or placebo ( n=54) twice daily for 12 weeks. Patients were excluded in case of comorbid serious medical conditions or neurologic disorders, comorbid psychiatric disorders other than methamphetamine dependence requiring specific treatment interventions, simultaneous positive urine test result for substances of abuse other than methamphetamine, smoking >3 days per week, simultaneous consumption of medications which are contraindicated or have interaction with riluzole. Results: Concerning primary outcomes, the cumulative mean number of attended weekly visits was higher in the riluzole arm compared with the placebo arm approaching a statistically significant difference (riluzole, median (range)=13.00 (2.00–13.00); placebo=4.00 (2.00–13.00); Mann-Whitney U=505.00, p-value=0.073), and the weekly measured rate of positive methamphetamine urine test results was significantly lower in the riluzole arm by the end of the study (riluzole=1 (5.00%), placebo=9 (45.00%), p-value=0.004). Patients in the riluzole arm experienced significantly greater improvement on all the craving, withdrawal, and depression measures regarding mean score changes from baseline to endpoint. No significant difference was detected between the two arms in terms of incidence of adverse events. Conclusion: Future randomized clinical trials are needed to investigate proper dosing strategy in a more inclusive sample.