bluuebunny/crossref_metadata_2025_split huggingface dataset:
Village-Integrated Eye Worker trial (VIEW): rationale and design of a cluster-randomised trial to prevent corneal ulcers in resource-limited settings
Authors: O’Brien Kieran S , Byanju Raghunandan , Kandel Ram Prasad , Poudyal Bimal , Gautam Mariya , Gonzales John A , Porco Travis C , Whitcher John P , Srinivasan Muthiah , Upadhyay Madan , Lietman Thomas M , Keenan Jeremy D 
Published: August 2018

IntroductionCorneal opacity is a leading cause of blindness worldwide. In resource-limited settings, untreated traumatic corneal abrasions may result in infection and ultimately, opacity. Although antimicrobial treatment of corneal ulcers may successfully cure infections, the scarring that accompanies the resolution of infection can still result in visual impairment. Prevention may be the optimal approach for reducing corneal blindness. Studies have employed community health workers to provide prompt administration of antimicrobials after corneal abrasions to prevent infections, but these studies were not designed to determine the effectiveness of such a programme.Methods and analysisThe Village-Integrated Eye Worker trial (VIEW) is a cluster-randomised trial designed to assess the effectiveness of a community health worker intervention to prevent corneal ulcers. Twenty-four Village Development Committees (VDCs) in Nepal were randomised to receive a corneal ulcer prevention programme or to no intervention. Female Community Health Volunteers (FCHVs) in intervention VDCs are trained to diagnose corneal abrasions, provide antimicrobials and to refer participants when needed. An annual census is conducted over 3 years in all study VDCs to assess the incidence of corneal ulceration via corneal photography (primary outcome). Masked outcome assessors grade corneal photographs to determine the presence or absence of incident corneal opacities. The primary analysis is negative binomial regression to compare the incidence of corneal ulceration by study arm.Ethics and disseminationThe University of California San Francisco Committee on Human Research, Nepal Netra Jyoti Sangh and the Nepal Health Research Council have given ethical approval for the trial. The results of this trial will be presented at local and international meetings and submitted to peer-reviewed journals for publication.Trial registration numberNCT01969786; Pre-results.
Morita Therapy for depression (Morita Trial): a pilot randomised controlled trial
Authors: Sugg Holly Victoria Rose , Richards David A , Frost Julia 
Published: August 2018

ObjectiveTo address uncertainties prior to conducting a fully powered randomised controlled trial of Morita Therapy plus treatment as usual (TAU) versus TAU alone, or to determine that such a trial is not appropriate and/or feasible.DesignPilot parallel group randomised controlled feasibility trial.Setting and participantsParticipants aged ≥18 years with Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV major depressive disorder, with or without DSM-IV anxiety disorder(s), recruited from general practice record searches in Devon, UK.InterventionsWe randomised participants on a 1:1 basis stratified by symptom severity, concealing allocation using a secure independent web-based system, to receive TAU (control) or 8–12 sessions of Morita Therapy, a Japanese psychological therapy, plus TAU (intervention).OutcomesRates of recruitment, retention and treatment adherence; variance and estimated between-group differences in follow-up scores (on the Patient Health Questionnaire 9 (PHQ-9) (depressive symptoms); Generalised Anxiety Disorder Questionnaire 7 (anxiety symptoms); Short Form 36 Health Survey Questionnaire/Work and Social Adjustment Scale (quality of life); Morita Attitudinal Scale for Arugamama (attitudes)) and their correlation with baseline scores.ResultsWe recruited 68 participants, 5.1% (95% CI 3.4% to 6.6%) of those invited (34 control; 34 intervention); 64/68 (94%; 95% CI 88.3% to 99.7%) provided 4-month follow-up data. Participants had a mean age of 49 years and mean PHQ-9 score of 16.8; 61% were female. Twenty-four of 34 (70.6%) adhered to the minimum treatment dose. The follow-up PHQ-9 (future primary outcome measure) pooled SD was 6.4 (95% CI 5.5 to 7.8); the magnitude of correlation between baseline and follow-up PHQ-9 scores was 0.42 (95% CI 0.19 to 0.61). Of the participants, 66.7% and 30.0% recovered in the intervention and control groups, respectively; 66.7% and 13.3% responded to treatment in the intervention and control groups, respectively.ConclusionsA large-scale trial of Morita Therapy would require 133 participants per group and is feasible with minor modifications to the pilot trial protocol. Morita Therapy shows promise in treating depression and may provide patients with a distinct alternative to current treatments.Trial registration numberISRCTN17544090; Pre-results.
Efficacy and tolerance of early administration of tranexamic acid in patients with cirrhosis presenting with acute upper gastrointestinal bleeding: a study protocol for a multicentre, randomised, double-blind, placebo-controlled trial (the EXARHOSE study)
Authors: Heidet Matthieu , Amathieu Roland , Audureau Etienne , Augusto Oriane , Nicolazo de Barmon Violaine , Rialland Amandine , Schmitz David , Pierrang François , Marty Jean , Chollet-Xémard Charlotte , Thirion Olivier , Jacob Line 
Published: August 2018

IntroductionThe management of acute upper gastrointestinal bleeding (UGIB) is challenging in patients with cirrhosis, as it is responsible for severe complications and high mortality rates. Tranexamic acid (TXA) may help control the bleeding by counterbalancing cirrhosis-related hyperfibrinolysis. Still, there is a lack of unbiased data to conclude on its efficacy. The aim of this study is to evaluate the efficacy of TXA in the early treatment of acute UGIB in patients with cirrhosis.Methods and analysisThis study is a multicentre, randomised, double-blind, placebo-controlled trial, for adult patients with cirrhosis presenting with an acute UGIB and allocated to one of two arms: TXA or placebo (saline). Physicians from emergency mobile services, emergency departments (EDs) or intensive care units (ICUs) can include patients. Besides study intervention, standard care for UGIB will be performed as recommended. Intervention will consist an intravenous infusion of 10 mL of TXA (1 g) or saline, immediately followed by three identical intravenous infusions over 8 hours each (total dose of 4 g of TXA or 40 mL of placebo over 24 hours). Main analyses will be conducted in intention to treat on every patient included, then in modified intention to treat on patients with underlying lesion of portal hypertension visualised by endoscopy. The main objective is to show efficacy of TXA until day 5 on a composite criterion (bleeding control, rebleeding episodes and mortality). Secondary objectives aim at showing the efficacy of TXA on each individual component of the main outcome measure and others at 6 weeks and later (transjugular intrahepatic portosystemic shunt procedure, cirrhosis-specific complications, length of stay in ICU and in hospital, safety and tolerance of TXA, liver transplantation). Included patients will be followed up to 1 year after inclusion.500 patients will be necessary to show a reduction in the prevalence of the primary outcome from 30% to 18% with a bilateral alpha risk of 5% and a power of 80%.Ethics and disseminationEthical approval has been obtained from the Comité de Protection des Personnes Ile-de-France 1 (CPP-IDF1). Results will be disseminated via publications in peer-review medical journals and scientific forums.Protocol versionThis protocol is based on the latest version, as established on 11 October 2017 and validated by the IRB CPP Ile-de-France 1.Trial registration numberNCT03023189.
Social tenants’ health: evaluating the effectiveness of landlord interventions
Authors: Cheshire Paul Charles , Gibbons Stephen , Mouland Jemma 
Published: August 2018

BackgroundThe National Health Service (NHS) scores well internationally on access to healthcare. But access has been measured on methods likely to undersample the more disadvantaged. Social landlords have access to more disadvantaged groups and may be able to improve health outcomes for their tenants and reduce their NHS usage by simple interventions.MethodsThis is a randomised controlled trial of 547 London social housing ‘general needs’ tenants over 50 years of age. Participants were given a health assessment, then split into a control group or one of two treated groups. Following early assessment 25 participants had to be withdrawn to receive intensive treatment because of currently untreated major health problems. Participants were followed up over 18 months and changes in health outcomes and NHS usage measured.ResultsCompared with the control the most intensively treated group showed non-significant improvements on health outcomes but a significant reduction in NHS resource use, on conventional costings worth some £760 per person. All 25 participants transferred to the most intensively treated group after their early health assessments showed improvement on all health outcomes at final assessment, but these improvements were not statistically significant.ConclusionsDrawing a sample from disadvantaged but not the most seriously disadvantaged groups in London revealed 4.5% of the population to have very serious untreated health problems. The reason for lack of treatment was mainly non-registration with a general practitioner or psychiatric issues. Simple interventions to a targeted group were found to produce significant reductions in NHS usage and other, although non-significant, health benefits.Trial registration numberIDISRCTN96259142.
Synthetic control methodology as a tool for evaluating population-level health interventions
Authors: Bouttell Janet , Craig Peter , Lewsey James , Robinson Mark , Popham Frank 
Published: August 2018

BackgroundMany public health interventions cannot be evaluated using randomised controlled trials so they rely on the assessment of observational data. Techniques for evaluating public health interventions using observational data include interrupted time series analysis, panel data regression-based approaches, regression discontinuity and instrumental variable approaches. The inclusion of a counterfactual improves causal inference for approaches based on time series analysis, but the selection of a suitable counterfactual or control area can be problematic. The synthetic control method builds a counterfactual using a weighted combination of potential control units.MethodsWe explain the synthetic control method, summarise its use in health research to date, set out its advantages, assumptions and limitations and describe its implementation through a case study of life expectancy following German reunification.ResultsAdvantages of the synthetic control method are that it offers an approach suitable when there is a small number of treated units and control units and it does not rely on parallel preimplementation trends like difference in difference methods. The credibility of the result relies on achieving a good preimplementation fit for the outcome of interest between treated unit and synthetic control. If a good preimplementation fit is established over an extended period of time, a discrepancy in the outcome variable following the intervention can be interpreted as an intervention effect. It is critical that the synthetic control is built from a pool of potential controls that are similar to the treated unit. There is currently no consensus on what constitutes a ‘good fit’ or how to judge similarity. Traditional statistical inference is not appropriate with this approach, although alternatives are available. From our review, we noted that the synthetic control method has been underused in public health.ConclusionsSynthetic control methods are a valuable addition to the range of approaches for evaluating public health interventions when randomisation is impractical. They deserve to be more widely applied, ideally in combination with other methods so that the dependence of findings on particular assumptions can be assessed.
At-risk children with asthma (ARC): a systematic review
Authors: Buelo Audrey , McLean Susannah , Julious Steven , Flores-Kim Javier , Bush Andy , Henderson John , Paton James Y , Sheikh Aziz , Shields Michael , Pinnock Hilary 
Published: August 2018

IntroductionAsthma attacks are responsible for considerable morbidity and may be fatal. We aimed to identify and weight risk factors for asthma attacks in children (5–12 years) in order to inform and prioritise care.MethodsWe systematically searched six databases (May 2016; updated with forward citations January 2017) with no language/date restrictions. Two reviewers independently selected studies for inclusion, assessed study quality and extracted data. Heterogeneity precluded meta-analysis. Weighting was undertaken by an Expert Panel who independently assessed each variable for degree of risk and confidence in the assessment (based on study quality and size, effect sizes, biological plausibility and consistency of results) and then achieved consensus by discussion. Assessments were finally presented, discussed and agreed at a multidisciplinary workshop.ResultsFrom 16 109 records, we included 68 papers (28 cohort; 4 case-control; 36 cross-sectional studies). Previous asthma attacks were associated with greatly increased risk of attack (ORs between 2.0 and 4.1). Persistent symptoms (ORs between 1.4 and 7.8) and poor access to care (ORs between 1.2 and 2.3) were associated with moderately/greatly increased risk. A moderately increased risk was associated with suboptimal drug regimen, comorbid atopic/allergic disease, African-American ethnicity (USA), poverty and vitamin D deficiency. Environmental tobacco smoke exposure, younger age, obesity and low parental education were associated with slightly increased risk.DiscussionAssessment of the clinical and demographic features identified in this review may help clinicians to focus risk reduction management on the high-risk child. Population level factors may be used by health service planners and policymakers to target healthcare initiatives.Trial registration numberCRD42016037464.
Fiber ring-cavity laser based on semiconductor optical amplifier
Authors: Luo Min , Cao Wei , Chen Haiyan 
Published: August 2018

A fiber ring-cavity laser based on InP/InGaAsP multi-quantum wells semiconductor optical amplifier is proposed and experimentally demonstrated. The laser uses InP/InGaAsP multi-quantum as well as the gain medium and fiber Bragg grating as the wavelength selector. It’s demonstrated that the center wavelength of the output amplified spontaneous emission spectrum for the InP/InGaAsP multiple-quantum wells appears blue shift when its injection current increases. A lasing at central wavelength of 1549.66 nm with the maximum output power of 1.524 mW is obtained with electro-optical efficiency of 1.1% at injection current of 220 mA and the fiber Bragg grating operating temperature of 23[Formula: see text]C. The threshold injection current of the laser is 78 mA. When the operating temperature of fiber Bragg grating increases from 8[Formula: see text]C to 28[Formula: see text]C, the center wavelength of output laser increases from 1549.27 to 1549.59 nm. It shows that the laser has good temperature stability.
Kub5-HeraRPRD1B Deficiency Promotes “BRCAness” and Vulnerability to PARP Inhibition in BRCA-proficient Breast Cancers
Authors: Motea Edward A. , Fattah Farjana J. , Xiao Ling , Girard Luc , Rommel Amy , Morales Julio C. , Patidar Praveen , Zhou Yunyun , Porter Andrew , Xie Yang , Minna John D. , Boothman David A. 
Published: August 2018

Abstract

Purpose:
Identification of novel strategies to expand the use of PARP inhibitors beyond BRCA deficiency is of great interest in personalized medicine. Here, we investigated the unannotated role of Kub5-HeraRPRD1B (K-H) in homologous recombination (HR) repair and its potential clinical significance in targeted cancer therapy.

Experimental Design:
Functional characterization of K-H alterations on HR repair of double-strand breaks (DSB) were assessed by targeted gene silencing, plasmid reporter assays, immunofluorescence, and Western blots. Cell survival with PARP inhibitors was evaluated through colony-forming assays and statistically analyzed for correlation with K-H expression in various BRCA1/2 nonmutated breast cancers. Gene expression microarray/qPCR analyses, chromatin immunoprecipitation, and rescue experiments were used to investigate molecular mechanisms of action.

Results:
K-H expression loss correlates with rucaparib LD50 values in a panel of BRCA1/2 nonmutated breast cancers. Mechanistically, K-H depletion promotes BRCAness, where extensive upregulation of PARP1 activity was required for the survival of breast cancer cells. PARP inhibition in these cells led to synthetic lethality that was rescued by wild-type K-H reexpression, but not by a mutant K-H (p.R106A) that weakly binds RNAPII. K-H mediates HR by facilitating recruitment of RNAPII to the promoter region of a critical DNA damage response and repair effector, cyclin-dependent kinase 1 (CDK1).

Conclusions:
Cancer cells with low K-H expression may have exploitable BRCAness properties that greatly expand the use of PARP inhibitors beyond BRCA mutations. Our results suggest that aberrant K-H alterations may have vital translational implications in cellular responses/survival to DNA damage, carcinogenesis, and personalized medicine.
Some Critical Comments on Zimmerman’s Ignorance and Moral Obligation
Authors: Bykvist Krister 
Published: August 2018

In his recent book, Michael Zimmerman continues to defend the Prospective View, according to which moral obligation depends on evidence about both empirical and evaluative factors. In my commentary, I shall first focus on Zimmerman’s framework in which different moral theories are defined and distinguished. I argue that Zimmerman fails to formulate a clear and coherent distinction between The Prospective View and the Objective View, which he rejects. Then I turn to the so-called constraint #2, a crucial premise in Zimmerman’s master argument against the Objective View. Here I argue that it should be given up so that we can give the right verdict in cases of fundamental moral uncertainty. More specifically, I shall argue that a morally conscientious agent can rationally choose the option that is guaranteed to be morally wrong in a Jackson-case of fundamental moral uncertainty. Finally, I shall argue that the Prospective View, in its most recent guise – according to which moral obligation depends on empirical and evaluative evidence the agent has actually availed herself of – has very troubling substantive implications that go against all traditional moral theories, as well as an earlier version of Zimmerman’s Prospective View.
How the 21st Century Cures Act Can Mitigate the Ever Growing Problem of Mass Incarceration
Authors: Bard Jennifer S. 
Published: August 2018

By the time this article is published, our collective memory of the school shooting in Parkland, Florida could have faded or, even worse, been superseded by another mass shooting. Although details are still sparse, the perpetrator appears to be a 19-year-old man with a well-documented history of behavior disturbing enough to invoke referrals to mental health treatment, but not so disturbing as to warrant either commitment or even arrest. Unfortunately, the picture presented is one most familiar in the public imagination of how people with mental illness interact with the criminal justice system. In actuality, the violence of the perpetrator's crime makes him very untypical of the vast majority of people with mental illness who are no more likely to be violent than any other member of the general public.This Article will first describe the current situation in which people with mental illness have become part of the growing mass incarceration problem in the United States.
Real-World Data Analytics Fit for Regulatory Decision-Making
Authors: Schneeweiss Sebastian , Glynn Robert J. 
Published: August 2018

Healthcare database analyses (claims, electronic health records) have been identified by various regulatory initiatives, including the 21st Century Cures Act and Prescription Drug User Fee Act (“PDUFA”), as useful supplements to randomized clinical trials to generate evidence on the effectiveness, harm, and value of medical products in routine care. Specific applications include accelerated drug approval pathways and secondary indications for approved medical products. Such real-world data (“RWD”) analyses reflect how medical products impact health outside a highly controlled research environment. A constant stream of data from the routine operation of modern healthcare systems that can be analyzed in rapid cycles enables incremental evidence development for regulatory decision-making.Key evidentiary needs by regulators include 1) monitoring of medication performance in routine care, including the effectiveness, safety and value; 2) identifying new patient strata in which a drug may have added value or unacceptable harms; and 3) monitoring targeted utilization. Four broad requirements have been proposed to enable successful regulatory decision-making based on healthcare database analyses (collectively, “MVET”): Meaningful evidence that provides relevant and context-informed evidence sufficient for interpretation, drawing conclusions, and making decisions; valid evidence that meets scientific and technical quality standards to allow causal interpretations; expedited evidence that provides incremental evidence that is synchronized with the decision-making process; and transparent evidence that is audible, reproducible, robust, and ultimately trusted by decision-makers.Evidence generation systems that satisfy MVET requirements to a high degree will contribute to effective regulatory decision-making. Rapid-cycle analytics of healthcare databases is maturing at a time when regulatory overhaul increasingly demands such evidence. Governance, regulations, and data quality are catching up as the utility of this resource is demonstrated in multiple contexts.
Expansion of the Priority Review Voucher Program Under the 21st Century Cures Act: Implications for Innovation and Public Health
Authors: Sinha Michael S. , Jain Nina , Hwang Thomas , Kesselheim Aaron S. 
Published: August 2018

The U.S. federal government awards a priority review voucher (“PRV”) to a pharmaceutical manufacturer after the Food and Drug Administration (“FDA”) approves a product for one of a list of voucher-eligible indications. The voucher, which can be transferred or sold, allows the company to accelerate the review timeline of another product for any indication. The PRV program was proposed in 2006 as an incentive for research and development for neglected diseases, such as dengue and leishmaniasis.Neglected tropical diseases (“NTDs”) predominantly affect the world’s poorest populations and are associated with significant morbidity and mortality. Despite their global public health importance, neglected diseases were estimated to account for less than 1% of pharmaceutical research and development expenditures. The voucher program was intended to address this gap between investment and disease burden: “[t]he major obstacle to stimulating the R&D of new medicines for neglected diseases is lowincome nations' inability to pay for such medicines.” The voucher would provide an additional financial incentive to fund clinical development of these products without requiring additional appropriations from Congress.