bluuebunny/crossref_metadata_2025_split huggingface dataset:
OPtimising Treatment for MIld Systolic hypertension in the Elderly (OPTiMISE): protocol for a randomised controlled non-inferiority trial
Authors: Sheppard James P , Burt Jenni , Lown Mark , Temple Eleanor , Benson John , Ford Gary A , Heneghan Carl , Hobbs F D Richard , Jowett Sue , Little Paul , Mant Jonathan , Mollison Jill , Nickless Alecia , Ogburn Emma , Payne Rupert , Williams Marney , Yu Ly-Mee , McManus Richard J 
Published: October 2018

IntroductionRecent evidence suggests that larger blood pressure reductions and multiple antihypertensive drugs may be harmful in older people, particularly frail individuals with polypharmacy and multimorbidity. However, there is a lack of evidence to support deprescribing of antihypertensives, which limits the practice of medication reduction in routine clinical care. The aim of this trial is to examine whether antihypertensive medication reduction is possible in older patients without significant changes in blood pressure control at follow-up.Methods and analysisThis trial will use a primary care-based, open-label, randomised controlled trial design. A total of 540 participants will be recruited, aged ≥80 years, with systolic blood pressure <150 mm Hg and receiving ≥2 antihypertensive medications. Participants will have no compelling indication for medication continuation and will be considered to potentially benefit from medication reduction due to existing polypharmacy, comorbidity and frailty. Following a baseline appointment, individuals will be randomised to a strategy of medication reduction (intervention) with optional self-monitoring or usual care (control). Those in the intervention group will have one antihypertensive medication stopped. The primary outcome will be to determine if a reduction in medication can achieve a proportion of participants with clinically safe blood pressure levels at 12-week follow-up (defined as a systolic blood pressure <150 mm Hg), which is non-inferior (within 10%) to that achieved by the usual care group. Qualitative interviews will be used to understand the barriers and facilitators to medication reduction. The study will use economic modelling to predict the long-term effects of any observed changes in blood pressure and quality of life.Ethics and disseminationThe protocol, informed consent form, participant information sheet and all other participant facing material have been approved by the Research Ethics Committee (South Central—Oxford A; ref 16/SC/0628), Medicines and Healthcare products Regulatory Agency (ref 21584/0371/001–0001), host institution(s) and Health Research Authority. All research outputs will be published in peer-reviewed journals and presented at national and international conferences.Trial registration numberEudraCT 2016-004236-38;ISRCTN97503221; Pre-results.
Health information technology uses for primary prevention in preventive medicine: a scoping review protocol
Authors: Alturkistani Abrar , Majeed Azeem , Car Josip , Brindley David , Wells Glenn , Meinert Edward 
Published: October 2018

IntroductionThe use of health information technologies (HITs) has been associated with positive benefits such as improved health outcomes and improved health services. Results from empirical studies reported potential benefits of HITs in preventive medicine measures such as primary prevention. This review will examine the broad range of HITs and their uses and effectiveness in primary prevention.Methods and analysisWe will conduct searches in relevant databases (MEDLINE, EMBASE, the Cochrane Methodology Register, Cochrane Database of Systematic Reviews, CINAHL, SCOPUS and Web of Science) using Arksey and O’Malley’s scoping review methodology. The scoping review will include all study designs to identify the literature on HIT uses. Two reviewers will independently screen the literature following our screening criteria and using a data abstraction form. Findings will be summarised quantitatively (using numerical counts of HITs) and qualitatively (using narrative synthesis).Ethics and disseminationThe study will synthesise data from published literature and will not require an ethical approval. The results of the review will be disseminated through a peer-reviewed journal.
Plasma concentrations of second-line antituberculosis drugs in relation to minimum inhibitory concentrations in multidrug-resistant tuberculosis patients in China: a study protocol of a prospective observational cohort study
Authors: Davies Forsman Lina , Niward Katarina , Hu Yi , Zheng Rongrong , Zheng Xubin , Ke Ran , Cai Weiping , Hong Chao , Li Yang , Gao Yazhou , Werngren Jim , Paues Jakob , Kuhlin Johanna , Simonsson Ulrika S H , Eliasson Erik , Alffenaar Jan-Willem , Mansjö Mikael , Hoffner Sven , Xu Biao , Schön Thomas , Bruchfeld Judith 
Published: October 2018

IntroductionIndividualised treatment through therapeutic drug monitoring (TDM) may improve tuberculosis (TB) treatment outcomes but is not routinely implemented. Prospective clinical studies of drug exposure and minimum inhibitory concentrations (MICs) in multidrug-resistant TB (MDR-TB) are scarce. This translational study aims to characterise the area under the concentration–time curve of individual MDR-TB drugs, divided by the MIC forMycobacterium tuberculosisisolates, to explore associations with markers of treatment progress and to develop useful strategies for clinical implementation of TDM in MDR-TB.Methods and analysisAdult patients with pulmonary MDR-TB treated in Xiamen, China, are included. Plasma samples for measure of drug exposure are obtained at 0, 1, 2, 4, 6, 8 and 10 hours after drug intake at week 2 and at 0, 4 and 6 hours during weeks 4 and 8. Sputum samples for evaluating time to culture positivity and MIC determination are collected at days 0, 2 and 7 and at weeks 2, 4, 8 and 12 after treatment initiation. Disease severity are assessed with a clinical scoring tool (TBscore II) and quality of life evaluated using EQ-5D-5L. Drug concentrations of pyrazinamide, ethambutol, levofloxacin, moxifloxacin, cycloserine, prothionamide and para-aminosalicylate are measured by liquid chromatography tandem-mass spectrometry and the levels of amikacin measured by immunoassay. Dried blood spot on filter paper, to facilitate blood sampling for analysis of drug concentrations, is also evaluated. The MICs of the drugs listed above are determined using custom-made broth microdilution plates and MYCOTB plates with Middlebrook 7H9 media. MIC determination of pyrazinamide is performed in BACTEC MGIT 960.Ethics and disseminationThis study has been approved by the ethical review boards of Karolinska Institutet, Sweden and Fudan University, China. Informed written consent is given by participants. The study results will be submitted to a peer-reviewed journal.Trial registration numberNCT02816931; Pre-results.
Financial Incentives to Increase Uptake of Pediatric HIV Testing (FIT): study protocol for a randomised controlled trial in Kenya
Authors: Wagner Anjuli D , Njuguna Irene N , Neary Jillian , Omondi Vincent O , Otieno Verlinda A , Babigumira Joseph , Maleche-Obimbo Elizabeth , Wamalwa Dalton C , John-Stewart Grace C , Slyker Jennifer A 
Published: October 2018

IntroductionIndex case testing (ICT) to identify HIV-infected children is efficient but has suboptimal uptake. Financial incentives (FI) have overcome financial barriers in other populations by offsetting direct and indirect costs. A pilot study found FI to be feasible for motivating paediatric ICT among HIV-infected female caregivers. This randomised trial will determine the effectiveness of FI to increase uptake of paediatric ICT.Methods and analysisThe Financial Incentives to Increase Uptake of Pediatric HIV Testing trial is a five-arm, unblinded, randomised controlled trial that determines whether FI increases timely uptake of paediatric ICT. The trial will be conducted in multiple public health facilities in western Kenya. Each HIV-infected adult enrolled in HIV care will be screened for eligibility: primary caregiver to one or more children of unknown HIV status aged 0–12 years. Eligible caregivers will be individually randomised at the time of recruitment in equal 1:1:1:1:1 allocation to one of five arms (US$0 (control), US$1.25, US$2.50, US$5.00 and US$10.00). The trial aims to randomise 800 caregivers. Incentives will be disbursed at the time of child HIV testing using mobile money transfer or cash. Arms will be compared in terms of the proportion of adults who complete testing for at least one child within 2 months of randomisation and time to testing. A cost-effectiveness analysis of FI for paediatric ICT will also be conducted.Ethics and disseminationThis study was reviewed and approved by the University of Washington Institutional Review Board and the Kenyatta National Hospital Ethics and Research Committee. Trial results will be disseminated to healthcare workers at study sites, regional and national policymakers, and with patient populations at study sites (regardless of enrolment in the trial). Randomised trials of caregiver-child FI interventions pose unique study design, ethical and operational challenges, detailed here as a resource for future investigations.Trial registration numberNCT03049917; Pre-results.
16p13.11 microduplication in 45 new patients: refined clinical significance and genotype–phenotype correlations
Authors: Allach El Khattabi Laïla , Heide Solveig , Caberg Jean-Hubert , Andrieux Joris , Doco Fenzy Martine , Vincent-Delorme Caroline , Callier Patrick , Chantot-Bastaraud Sandra , Afenjar Alexandra , Boute-Benejean Odile , Cordier Marie Pierre , Faivre Laurence , Francannet Christine , Gerard Marion , Goldenberg Alice , Masurel-Paulet Alice , Mosca-Boidron Anne-Laure , Marle Nathalie , Moncla Anne , Le Meur Nathalie , Mathieu-Dramard Michèle , Plessis Ghislaine , Lesca Gaetan , Rossi Massimiliano , Edery Patrick , Delahaye-Duriez Andrée , De Pontual Loïc , Tabet Anne Claude , Lebbar Aziza , Suiro Lesley , Ioos Christine , Natiq Abdelhafid , Chafai Elalaoui Siham , Missirian Chantal , Receveur Aline , François-Fiquet Caroline , Garnier Pascal , Yardin Catherine , Laroche Cécile , Vago Philippe , Sanlaville Damien , Dupont Jean Michel , Benzacken Brigitte , Pipiras Eva 
Published: October 2018

BackgroundThe clinical significance of 16p13.11 duplications remains controversial while frequently detected in patients with developmental delay (DD), intellectual deficiency (ID) or autism spectrum disorder (ASD). Previously reported patients were not or poorly characterised. The absence of consensual recommendations leads to interpretation discrepancy and makes genetic counselling challenging. This study aims to decipher the genotype–phenotype correlations to improve genetic counselling and patients’ medical care.MethodsWe retrospectively analysed data from 16 013 patients referred to 12 genetic centers for DD, ID or ASD, and who had a chromosomal microarray analysis. The referring geneticists of patients for whom a 16p13.11 duplication was detected were asked to complete a questionnaire for detailed clinical and genetic data for the patients and their parents.ResultsClinical features are mainly speech delay and learning disabilities followed by ASD. A significant risk of cardiovascular disease was noted. About 90% of the patients inherited the duplication from a parent. At least one out of four parents carrying the duplication displayed a similar phenotype to the propositus. Genotype–phenotype correlations show no impact of the size of the duplicated segment on the severity of the phenotype. However, NDE1 and miR-484 seem to have an essential role in the neurocognitive phenotype.ConclusionOur study shows that 16p13.11 microduplications are likely pathogenic when detected in the context of DD/ID/ASD and supports an essential role of NDE1 and miR-484 in the neurocognitive phenotype. Moreover, it suggests the need for cardiac evaluation and follow-up and a large study to evaluate the aortic disease risk.
Establishing an Efficient Care Paradigm for Trigger Finger
Authors: Usmani Rashad H. , Abrams Samuel S. , Merrell Gregory A. 
Published: October 2018

Background: To identify the time course for efficacy of corticosteroid injections in the treatment of trigger finger. Methods: A prospective single-center observational study was conducted, consisting of 38 patients with 41 trigger digits that were injected. Enrolled patients completed an initial Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire to determine the severity of their symptoms. Following the injection, patients were contacted at scheduled time points for up to 12 weeks to determine if, and when, objective resolution of symptoms occurred. Patients who received additional treatment, such as a second injection or surgery, and those who did not have objective relief of symptoms by 12 weeks were classified as failed. Upon symptom resolution or injection failure, patients were given a DASH exit questionnaire. Results: 30 of 41 injected trigger digits resolved and 11 failed treatment with a single corticosteroid injection. The latest that any study participant experienced resolution of symptoms was 69 days. At 38 days, the rate of resolution of the study population slowed significantly. Conclusions: Although symptomatic resolution of trigger finger from a single corticosteroid injection can occur early on, a follow-up of 4 weeks (28 days) does not allow enough time for symptom resolution. The earliest a surgeon and patient should consider a secondary treatment is at 38 days. After 69 days without resolution, both surgeon and patient can be confident that further treatment is needed.
Manipulating fenestrations in young and old liver sinusoidal endothelial cells
Authors: Hunt Nicholas J. , Lockwood Glen P. , Warren Alessandra , Mao Hong , McCourt Peter A. G. , Le Couteur David G. , Cogger Victoria C. 
Published: October 2018

Fenestrations are pores within liver sinusoidal endothelial cells (LSECs) that enable the transfer of substrates (particularly insulin and lipoproteins) between blood and hepatocytes. With increasing age, there are marked reductions in fenestrations, referred to as pseudocapillarization. Currently, fenestrations are thought to be regulated by vascular endothelial growth factor and nitric oxide (NO) pathways promoting remodeling of the actin cytoskeleton and cell membrane lipid rafts. We investigated the effects of drugs that act on these pathways on fenestrations in old (18–24 mo) and young mice (3–4 mo). Isolated LSECs were incubated with either cytochalasin 7-ketocholesterol, sildenafil, amlodipine, simvastatin, 2, 5-dimethoxy-4-iodoamphetamine (DOI), bosentan, TNF-related apoptosis-inducing ligand (TRAIL) or nicotinamide mononucleotide (NMN). LSECs were visualized under scanning electron microscopy to quantify fenestration porosity, diameter, and frequency, as well as direct stochastic optical reconstruction microscopy to examine actin and NO synthase. In young and old LSECs, fenestration porosity, diameter and frequency were increased by 7-ketocholesterol, while porosity and/or frequency were increased with NMN, sildenafil, amlodipine, TRAIL, and cytochalasin D. In old mice only, bosentan and DOI increased fenestration porosity and/or frequency. Modification of the actin cytoskeleton was observed with all agents that increased fenestrations, while NO synthase was only increased by sildenafil, amlodipine, and TRAIL. In conclusion, agents that target NO, actin, or lipid rafts promote changes in fenestrations in mice LSECs. Regulation of fenestrations occurs via both NO-dependent and independent pathways. This work indicates that age-related defenestration can be reversed pharmacologically, which has potential translational relevance for dyslipidemia and insulin resistance.NEW & NOTEWORTHY We demonstrate the effects of multiple nitric oxide-dependent and -independent pharmaceutical agents on fenestrations of the liver sinusoidal endothelium. Fenestrations are reorganized in response to nicotinamide mononucleotide, sildenafil, amlodipine, and TNF-related apoptosis-inducing ligand. This work indicates that age-related defenestration can be reversed pharmacologically, which has potential translational relevance for dyslipidemia and insulin resistance in old age.
A nutrient cocktail prevents lipid metabolism alterations induced by 20 days of daily steps reduction and fructose overfeeding: result from a randomized study
Authors: Damiot Anthony , Demangel Rémi , Noone John , Chery Isabelle , Zahariev Alexandre , Normand Sylvie , Brioche Thomas , Crampes François , de Glisezinski Isabelle , Lefai Etienne , Bareille Marie Pierre , Chopard Angèle , Drai Jocelyne , Collin-Chavagnac Delphine , Heer Martina , Gauquelin-Koch Guillemette , Prost Michel , Simon Patrick , Py Guillaume , Blanc Stéphane , Simon Chantal , Bergouignan Audrey , O’Gorman Donal J. 
Published: October 2018

Physical inactivity and sedentary behaviors are independent risk factors for numerous diseases. We examined the ability of a nutrient cocktail composed of polyphenols, omega-3 fatty acids, vitamin E, and selenium to prevent the expected metabolic alterations induced by physical inactivity and sedentary behaviors. Healthy trained men ( n = 20) (averaging ∼14,000 steps/day and engaged in sports) were randomly divided into a control group (no supplementation) and a cocktail group for a 20-day free-living intervention during which they stopped exercise and decreased their daily steps (averaging ∼3,000 steps/day). During the last 10 days, metabolic changes were further triggered by fructose overfeeding. On days 0, 10, and 20, body composition (dual energy X-ray), blood chemistry, glucose tolerance [oral glucose tolerance test (OGTT)], and substrate oxidation (indirect calorimetry) were measured. OGTT included 1% fructose labeled with (U-13C) fructose to assess liver de novo lipogenesis. Histological changes and related cellular markers were assessed from muscle biopsies collected on days 0 and 20. While the cocktail did not prevent the decrease in insulin sensitivity and its muscular correlates induced by the intervention, it fully prevented the hypertriglyceridemia, the drop in fasting HDL and total fat oxidation, and the increase in de novo lipogenesis. The cocktail further prevented the decrease in the type-IIa muscle fiber cross-sectional area and was associated with lower protein ubiquitination content. The circulating antioxidant capacity was improved by the cocktail following the OGTT. In conclusion, a cocktail of nutrient compounds from dietary origin protects against the alterations in lipid metabolism induced by physical inactivity and fructose overfeeding. NEW & NOTEWORTHY This is the first study to test the efficacy of a novel dietary nutrient cocktail on the metabolic and physiological changes occurring during 20 days of physical inactivity along with fructose overfeeding. The main findings of this study are that 1) reduction in daily steps leads to decreased insulin sensitivity and total fat oxidation, resulting in hyperlipemia and increased de novo lipogenesis and 2) a cocktail supplement prevents the alterations on lipid metabolism.
Detecting Clouds Associated with Jet Engine Ice Crystal Icing
Authors: Haggerty Julie , Defer Eric , De Laat Adrianus , Bedka Kristopher , Moisselin Jean-Marc , Potts Rodney , Delanoë Julien , Parol Frédéric , Grandin Alice , Divito Stephanie 
Published: October 2018

AbstractIn the past two decades, more than 150 jet engine power-loss and damage events have been attributed to a phenomenon known as ice crystal icing (ICI). Ingestion of large numbers of ice particles into the engine core are thought to be responsible for these events, which typically occur at high altitudes near large convective systems in tropical air masses. In recent years, scientists, engineers, aviation regulators, and airlines from around the world have collaborated to better understand the relevant meteorological processes associated with ICI events, solve critical engineering problems, develop new certification standards, and devise mitigation strategies for the aviation industry. One area of research is the development of nowcasting techniques based on available remote sensing technology and numerical weather prediction (NWP) models to identify areas of high ice water content (IWC) and enable the provision of alerts to the aviation industry. Multiple techniques have been developed using geostationary and polar-orbiting satellite products, NWP model fields, and ground-based radar data as the basis for high-IWC products. Targeted field experiments in tropical regions with high incidence of ICI events have provided data for product validation and refinement of these methods. Beginning in 2015, research teams have assembled at a series of annual workshops to exchange ideas and standardize methods for evaluating performance of high-IWC detection products. This paper provides an overview of the approaches used and the current skill for identifying high-IWC conditions. Recommendations for future work in this area are also presented.
Australia’s ‘Better Access’ scheme: Has it had an impact on population mental health?
Authors: Jorm Anthony F 
Published: October 2018

Background: Australia introduced the Better Access scheme in late 2006, which resulted in a large increase in the provision of mental health services by general practitioners (GPs), clinical psychologists, other psychologists and allied health professionals. It is unknown whether this increase in services has had an effect on the mental health of the population. Methods: The following data were examined: per capita use of mental health services provided by GPs, clinical psychologists, other psychologists, allied health professionals and psychiatrists from 2006 to 2015 according to the Australian Government Department of Human Services; prevalence of psychological distress in adults (as measured by the K10) from National Health Surveys in 2001, 2004–2005, 2007–2008, 2011–2012 and 2014–2015; and the annual suicide rate from 2001 to 2015 according to the Australian Bureau of Statistics. Results: The large increase in the use of mental health services after the introduction of the Better Access scheme had no detectable effect on the prevalence of very high psychological distress or the suicide rate. Conclusion: Better Access has not had a detectable effect on the mental health of the Australian population.
Increased Frontal Lobe Volume as a Neural Correlate of Gray-Collar Offending
Authors: Ling Shichun , Raine Adrian , Yang Yaling , Schug Robert A. , Portnoy Jill , Ho Moon-Ho Ringo 
Published: October 2018

Objectives: A process model of white-collar crime postulates that the etiology of this form of crime is incomplete without consideration of individual differences in neurobiology. Based on prior research, this study tests the primary hypothesis that “gray-collar crime” (GCC; offending on the margin of more serious white-collar crimes) would be associated with increased frontal lobe volume. Secondary analyses explored which frontal subregions, if any, would be associated with gray-collar offending. Method: Gray-collar offending and blue-collar criminal offending were assessed in 129 community males. Total frontal lobe, anterior cingulate, superior frontal, middle frontal, inferior frontal, and orbitofrontal volumes were assessed using magnetic resonance imaging. Results: Increased frontal volume was associated with increased gray-collar offending. Frontal volume remained significant after controlling for ethnicity, age, intelligence, whole brain volume, and blue-collar crime covariates, explaining 4.6 percent of the variance in GCC. Within the frontal lobe, findings were localized to superior frontal and anterior cingulate cortex, both before and after controlling for covariates. Conclusions: Findings provide preliminary evidence of increased frontal volume as a neural correlate of gray-collar offending and support a process model which hypothesizes that frontal lobe volume may provide some individuals with an advantage in perpetrating criminal offenses in occupational and avocational settings.