bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the risk factors associated with conversion of intended deep anterior lamellar keratoplasty to penetrating keratoplasty
Authors: Myerscough James , Friehmann Asaf , Bovone Cristina , Mimouni Michael , Busin Massimo 
Published: September 2019

Background/aimsTo identify and evaluate risk factors associated with the need to convert intended deep anterior lamellar keratoplasty (DALK) to penetrating keratoplasty (PK).MethodsRetrospective institutional cohort study including all consecutive eyes undergoing intended DALK between May 2015 and October 2018 at ‘Villa Igea’ Hospital (Forli, Italy). The indications for surgery were categorised as (1) keratoconus without scarring; (2) keratoconus with scarring; (3) non-keratoconus without scarring; and (4) non-keratoconus with scarring. Multivariate binary logistic regression analysis was performed, introducing, as independent variables, those that reached a significance level of less than 0.05 in univariate analysis. The main outcome measure was whether or not conversion to a PK occurred.Results705 eyes were included, with conversion to PK occurring in 16.2% (n=114) of cases. The factors that remained significant in multivariate analysis were corneal scarring (OR=3.52, p<0.001), manual dissection (OR=42.66, p<0.001), type 2 bubble (OR=90.65, p<0.001) and surgeon inexperience (OR=10.86, p<0.001). A receiver operating characteristic (ROC) curve based on the factors significant in the multivariate binary logistic regression analysis achieved a sensitivity of 89.5% (95% CI 82.3% to 94.4%) and a specificity of 80.2% (95% CI 76.8% to 83.3%) with an area under the ROC curve of 0.91 (95% CI 0.88 to 0.93) (p<0.001)ConclusionOccurrence of a type 2 bubble, the need for manual dissection, the presence of scarring and surgeon inexperience are independent risk factors for the need to convert intended DALK to PK. Correct identification and management of the type of bubble achieved during pneumatic dissection is instrumental in minimising the rate of conversion to PK.
Protocol for the VAL-MAP 2.0 trial: a multicentre, single-arm, phase III trial to evaluate the effectiveness of virtual-assisted lung mapping by bronchoscopic dye injection and microcoil implementation in patients with small pulmonary nodules in Japan
Authors: Ueda Keiko , Uemura Yukari , Sato Masaaki 
Published: September 2019

IntroductionTumour localisation is important for successful resection of lung nodules with optimal resection margins in sublobar resection. Virtual-assisted bronchoscopic localisation technique combined with dye marking and microcoil placement (VAL-MAP 2.0) is a minimally invasive, virtual-assisted, bronchoscopic technique that combines dye marking and microcoil implementation. As indwelling microcoils can provide information on the depth from the lung surface, they can be applied for deeply located small lung tumours that are barely identifiable by surface dye marking. This proposed study will examine the effectiveness of VAL-MAP 2.0 in patients with small pulmonary nodules.Methods and analysisThis is a multicentre, prospective, single-arm, clinical trial. A total of 65 patients will be registered to undergo VAL-MAP 2.0 followed by thoracoscopic surgery. The primary outcome is successful resection, defined as resection of the lesion with optimal resection margins. The goal of the study is the achievement of a successful resection rate of 80%.Ethics and disseminationThe study was approved by the Clinical Research Review Boards of the University of Tokyo (approval number 218 003SP) for all institutes, and the Technical Review Board for Advanced Medicine Category B of the Ministry of Health, Labour and Welfare. Results of the primary and secondary endpoints will be submitted for publication in a peer-reviewed journal.Trial registration numberjRCTs031180099
Analysis of anticholinergic and sedative medicine effects on physical function, cognitive function, appetite and frailty: a cross-sectional study in Australia
Authors: Lim Renly , Kalisch Ellett Lisa M , Widagdo Imaina S , Pratt Nicole L , Roughead Elizabeth Ellen 
Published: September 2019

ObjectiveTo test the association between use of medicines with anticholinergic or sedative properties and physical function, cognitive function, appetite and frailty.Design, setting and participantsThis cross-sectional study analysed baseline data collected as part of the Australian Longitudinal Study of Ageing, a population-based cohort of 2087 participants aged 65 years or over living in South Australia.Main outcome measuresPhysical function was measured at baseline using measures including hand grip strength, walking speed, chair stands, activities of daily living and instrumental activities of daily living (IADL). Cognitive function was measured using Mini-Mental State Examination. Appetite was measured using Center for Epidemiologic Studies Depression question 2. Frailty was measured using frailty index. The association between use of anticholinergics or sedatives and physical or cognitive function, appetite, or frailty was assessed using analysis of covariance and ordinal or binary logistic regression.ResultsAlmost half of the population were using anticholinergics or sedatives (n=954, 45.7%). Use of anticholinergics was significantly associated with poorer grip strength, slower walking speed, poorer IADL and poorer appetite. Use of sedatives was significantly associated with poorer grip strength, slower walking speed and poorer IADL. We found no significant association between medicine use and cognitive function. Users of anticholinergics or sedatives were significantly more likely to be frail compared with non-users.ConclusionUse of medicines with anticholinergic or sedative properties is significantly associated with poorer physical function, poorer appetite and increased frailty. Early identification of signs and symptoms of deterioration associated with medicine use is particularly important in older people so that worsening frailty and subsequent adverse events are prevented.
Mental health specialist video consultations for patients with depression or anxiety disorders in primary care: protocol for a randomised controlled feasibility trial
Authors: Tönnies Justus , Hartmann Mechthild , Wensing Michel , Szecsenyi Joachim , Icks Andrea , Friederich Hans-Christoph , Haun Markus W 
Published: September 2019

IntroductionMost people suffering from depression and anxiety disorders are entirely treated in primary care. Due to growing challenges in ageing societies, for example, patients’ immobility and multimorbidity, the transition to specialised care becomes increasingly difficult. Although the co-location of general practitioners and mental health specialists improves the access to psychosocial care, integrated in-person approaches are not practical for rural and single-doctor practices with limited personnel and financial resources. Treating primary care patients via internet-based video consultations by remotely located mental health specialists bears the potential to overcome structural barriers and provide low-threshold care. The aim of this randomised controlled feasibility trial is to investigate the feasibility of implementing of mental health specialist video consultations in primary care practices.Methods and analysisFifty primary care patients with significant depression and/or anxiety symptomatology will be randomised in two groups receiving either the treatment as usual as provided by their general practitioner or up to five video consultations conducted by a mental health specialist. The video consultations focus on (1) systematic diagnosis plus proactive monitoring using validated clinical rating scales, (2) the establishment of an effective working alliance and (3) a stepped-care algorithm within integrated care adjusting treatments based on clinical outcomes. We will investigate the following outcomes: effectiveness of the recruitment strategies, patient acceptance of randomisation, practicability of the technical and logistical processes related to implementing video consultations in the practices’ workflows, feasibility of the data collection and clinical parameters.Ethics and disseminationThis trial has undergone ethical scrutiny and has been approved by the Medical Faculty of the University of Heidelberg Ethics Committee (S-634/2018). The findings will be disseminated to the research community through presentations at conferences and publications in scientific journals. This feasibility trial will prepare the ground for a large-scale, fully powered randomised controlled trial.Trial registration numberDRKS00015812.
Dealing with maedi visna in UK sheep flocks
Authors: Ogden Nicky , Davies Peers , Lovatt Fiona 
Published: September 2019

Background: Maedi visna (MV) is considered to be one of the ‘iceberg diseases’ of sheep; a group of infectious, production‐limiting diseases which are endemic to the UK. Characterised by slow, progressive onset, these diseases lie undetected and can have a large impact on flock efficiency. This group of diseases also includes border disease, caseous lymphadenitis, ovine Johne's disease and ovine pulmonary adenocarcinoma. The prevalence and effects of these diseases within different UK flock types remains unknown.Aim of the article: To highlight the increasing importance of MV within the national flock. Here, we discuss the production effects, diagnosis and control options for MV.
Importance of systematic deliberation and stakeholder presence: a national study of clinical ethics committees
Authors: Magelssen Morten , Pedersen Reidar , Miljeteig Ingrid , Ervik Håvard , Førde Reidun 
Published: September 2019

BackgroundCase consultation performed by clinical ethics committees (CECs) is a complex activity which should be evaluated. Several evaluation studies have reported stakeholder satisfaction in single institutions. The present study was conducted nationwide and compares clinicians’ evaluations on a range of aspects with the CEC’s own evaluation.MethodsProspective questionnaire study involving case consultations at 19 Norwegian CECs for 1 year, where consultations were evaluated by CECs and clinicians who had participated.ResultsEvaluations of 64 case consultations were received. Cases were complex with multiple ethical problems intertwined. Clinicians rated the average CEC consult highly, being both satisfied with the process and perceiving it to be useful across a number of aspects. CEC evaluations corresponded well with those of clinicians in a large majority of cases. Having next of kin/patients present was experienced as predominantly positive, though practised by only half of the CECs. The educational function of the consult was evaluated more positively when the CEC used a systematic deliberation method.ConclusionsCEC case consultation was found to be a useful service. The study is also a favourable evaluation of the Norwegian CEC system, implying that it is feasible to implement well-functioning CECs on a large scale. There are good reasons to involve the stakeholders in the consultations as a main rule.
Hypoxia preconditioning promotes endurance exercise capacity of mice by activating skeletal muscle Nrf2
Authors: Wang Linjia , Yang Simin , Yan Lu , Wei Hao , Wang Jianxiong , Yu Siwang , Kong Ah-Ng Tony , Zhang Ying 
Published: September 2019

Elite endurance athletes are used to train under hypoxic/high-altitude conditions, which can elicit certain stress responses in skeletal muscle and helps to improve their physical performance. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates cellular redox homeostasis and metabolism in skeletal muscle, playing important roles in adaptation to various stresses. In this study, Nrf2 knockout (KO) and wild-type (WT) mice were preconditioned to 48 h of hypoxia exposure (11.2% oxygen), and the effects of hypoxia preconditioning (HP) on exercise capacity and exercise-induced changes of antioxidant status, energetic metabolism, and mitochondrial adaptation in skeletal muscle were evaluated. Nrf2 knockout (KO) and wild-type (WT) mice were exposed to normoxia or hypoxia for 48 h before taking incremental treadmill exercise to exhaustion under hypoxia. The skeletal muscles were collected immediately after the incremental treadmill exercise to evaluate the impacts of HP and Nrf2 on the exercise-induced changes. The results indicate the absence of Nrf2 did not affect exercise capacity, although the mRNA expression of certain muscular genes involved in antioxidant, glycogen and fatty acid catabolism was decreased in Nrf2 KO mice. However, 48-h HP enhanced exercise capacity in WT mice but not in Nrf2 KO mice, and the exercise capacity of WT mice was significantly higher than that of Nrf2 KO mice. These findings suggest HP promotes exercise capacity of mice with the participation of the Nrf2 signal in skeletal muscle.NEW & NOTEWORTHY Hypoxia preconditioning (HP) activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signal, which was involved in HP-elicited adaptation responses to hypoxia, oxidative, and metabolic stresses in skeletal muscle. On the other hand, Nrf2 deficiency abolished the enhanced exercise capacity after the 48-h HP. Our results indicate that Nrf2 plays an essential role in the exercise capacity-enhancing effect of HP, possibly by modulating muscular antioxidative responses, the mRNA expression of muscular genes involved in glycogen and fatty acid metabolism, as well as mitochondrial biogenesis, and through the cross talk with AMPK and hypoxia-inducible factor-1α signaling.
Race/Ethnicity and Accuracy of Self-Reported Female First-Degree Family History of Breast and Other Cancers in the Northern California Breast Cancer Family Registry
Authors: John Esther M. , Canchola Alison J. , Sangaramoorthy Meera , Koo Jocelyn , Whittemore Alice S. , West Dee W. 
Published: September 2019

Abstract

Background:
Few studies have evaluated accuracy of self-reported family history of breast and other cancers in racial/ethnic minorities.

Methods:
We assessed the accuracy of cancer family history reports by women with breast cancer (probands) from the Northern California Breast Cancer Family Registry compared with 2 reference standards: personal cancer history reports by female first-degree relatives and California Cancer Registry records.

Results:
Probands reported breast cancer in first-degree relatives with high accuracy, but accuracy was lower for other cancers. Sensitivity (percentage correctly identifying relatives with cancer) was 93% [95% confidence interval (CI), 89.5–95.4] when compared with the relatives' self-report of breast cancer as the reference standard and varied little by proband race/ethnicity and other demographic factors, except for marginally lower sensitivity for Hispanic white probands (87.3%; 95% CI, 78.0–93.1; P = 0.07) than non-Hispanic white probands (95.1%; 95% CI, 88.9–98.0). Accuracy was also high when compared with cancer registry records as the reference standard, with a sensitivity of 95.5% (95% CI, 93.4–96.9) for breast cancer, but lower sensitivity for Hispanic white probands (91.2%; 95% CI, 84.4–95.2; P = 0.05) and probands with low English language proficiency (80%; 95% CI, 52.8–93.5; P &lt; 0.01).

Conclusions:
Non-Hispanic white, African American, and Asian American probands reported first-degree breast cancer family history with high accuracy, although sensitivity was lower for Hispanic white probands and those with low English language proficiency.

Impact:
Self-reported family history of breast cancer in first-degree relatives is highly accurate and can be used as a reliable standard when other validation methods are not available.
Vaccination of Young Women Decreases Human Papillomavirus Transmission in Heterosexual Couples: Findings from the HITCH Cohort Study
Authors: Wissing Michel D. , Burchell Ann N. , El-Zein Mariam , Tellier Pierre-Paul , Coutlée François , Franco Eduardo L. 
Published: September 2019

Abstract

Background:
Vaccination against human papillomaviruses (HPV) prevents HPV infections and, consequently, cervical lesions. However, the effect of vaccination on HPV transmission within couples is unknown.

Methods:
We used data from HITCH, a prospective cohort study of heterosexual couples (women ages 18–24 years) in Montreal, 2005 to 2013. Vaccination history was self-reported. Genital samples were tested for HPV DNA by PCR (linear array). Type-specific viral loads were quantified using real-time PCR. OR and HR were estimated using multilevel mixed-effects logistic regression and a parametric model for interval- censored survival-time data, respectively. Differences in viral loads were evaluated using the Friedman ANOVA test.

Results:
Among 497 couples, 12, 16, and 35 women received 1, 2, or 3 vaccination doses at baseline, respectively. Median age at vaccination was 18 years. Most women (92.1%) had their first coitus before vaccination. At baseline, partner concordance of persistent HPV6/11/16/18 infections was lower in vaccinated than unvaccinated women [adjusted OR = 0.10; 95% confidence interval (CI), 0.01–0.65] but not for non α7/α9/α10-HPV types (adjusted OR = 1.00; 95% CI, 0.44–2.29). Incidence of persistent α7/α9/α10 HPV types in women was inversely associated with vaccination status at baseline (adjusted HR = 0.12; 95% CI, 0.03–0.47). Likewise, male partners of vaccinated women had a lower incidence of α7/α9/α10 HPV infections (adjusted OR = 0.22; 95% CI, 0.05–0.95). Vaccinated women with HPV 6/11/16/18 infections had lower viral loads (P = 0.001) relative to unvaccinated women.

Conclusions:
Vaccination of sexually active women significantly reduced transmission of α7/α9/α10 HPV types in heterosexual couples.

Impact:
These results underscore and quantify the positive effect of HPV vaccination on HPV transmission within heterosexual couples.
Serum miR-223: A Validated Biomarker for Detection of Early-Stage Non–Small Cell Lung Cancer
Authors: D'Antona Paola , Cattoni Maria , Dominioni Lorenzo , Poli Albino , Moretti Francesca , Cinquetti Raffaella , Gini Elisabetta , Daffrè Elisa , Noonan Douglas M. , Imperatori Andrea , Rotolo Nicola , Campomenosi Paola 
Published: September 2019

Abstract

Background:
The published circulating miRNA signatures proposed for early-stage non–small cell lung cancer (NSCLC) detection are inconsistent and difficult to replicate. Reproducibility and validation of an miRNA simple signature of NSCLC are prerequisites for translation to clinical application.

Methods:
The serum level of miR-223 and miR-29c, emerging from published studies, respectively, as a highly sensitive and a highly specific biomarker of early-stage NSCLC, was measured with droplet digital PCR (ddPCR) technique in an Italian cohort of 75 patients with stage I–II NSCLC and 111 tumor-free controls. By ROC curve analysis we evaluated the miR-223 and miR-29c performance in discerning NSCLC cases from healthy controls.

Results:
Reproducibility and robust measurability of the two miRNAs using ddPCR were documented. In a training set (40 stage I–II NSCLCs and 56 controls), miR-223 and miR-29c, respectively, showed an AUC of 0.753 [95% confidence interval (CI), 0.655–0.836] and 0.632 (95% CI, 0.527–0.729) in identifying NSCLC. Combination of miR-223 with miR-29c yielded an AUC of 0.750, not improved over that of miR-223 alone. Furthermore, in an independent blind set (35 stage I–II NSCLCs and 55 controls), we validated serum miR-223 as an effective biomarker of stage I–II NSCLC (AUC = 0.808; 95% CI, 0.712–0.884), confirming the miR-223 diagnostic performance reported by others in Chinese cohorts.

Conclusions:
Using ddPCR technology, miR-223 was externally validated as a reproducible, effective serum biomarker of early-stage NSCLC in ethnically different subjects. Combination with miR-29c did not improve the miR-223 diagnostic performance.

Impact:
Serum miR-223 determination may be proposed as a tool for refining NSCLC risk stratification, independent of smoking habit and age.
Efficacy and Safety of Ticagrelor in Comparison to Clopidogrel in Elderly Patients With ST‐Segment–Elevation Myocardial Infarctions
Authors: Schmucker Johannes , Fach Andreas , Mata Marin Luis Alberto , Retzlaff Tina , Osteresch Rico , Kollhorst Bianca , Hambrecht Rainer , Pohlabeln Hermann , Wienbergen Harm 
Published: September 2019

Background

Current guidelines recommend the new‐generation P2Y12‐inhibitor ticagrelor for patients with acute
ST
‐segment–elevation myocardial infarctions (
STEMIs
). The aim of the present study was to assess efficacy and safety of ticagrelor for elderly patients with
STEMI
(≥75 years) in an
all‐comers
STEMI
registry.

Methods and Results

Patients with
STEMI
, aged ≥75 years, treated with primary percutaneous coronary intervention and documented in the Bremen
STEMI
Registry between 2006 and 2017 entered analysis. The primary efficacy outcome, major adverse cardiac and cerebrovascular events, was defined as a composite of death, myocardial reinfarction, and stroke. The safety outcome was defined as any significant bleeding event within 1 year. To estimate benefit/risk ratio, net adverse clinical events (major adverse cardiac and cerebrovascular events+bleedings) were calculated. Outcomes were estimated in propensity score–matched cohorts to adjust for possible confounders. Of a total of 7466 patients with
STEMI
, 1087, aged ≥75 years, were selected, of which 552 (51%) received clopidogrel and 535 (49%) received ticagrelor, with similar age (80.9±4.6 versus 80.9±4.6 years) and sex (51% versus 50% female) distributions between treatment arms. The primary efficacy outcome occurred in 32.4% of patients treated with clopidogrel versus 25.5% treated with ticagrelor (
P
=0.015), with the 1‐year mortality rate at 26.8% versus 21.1% (
P
=0.035). Because there was no difference in the safety outcome (clopidogrel versus ticagrelor, 4.9% versus 5.1%; not significant), net adverse clinical events were higher for clopidogrel than for ticagrelor: 37.3% versus 30.6% (
P
=0.028). In a propensity score–matched model, the advantage for ticagrelor on major adverse cardiac and cerebrovascular events remained significant (hazard ratio, 0.69; 95%
CI
, 0.49‐0.97;
P
=0.03), whereas 1‐year‐mortality (hazard ratio, 0.89; 95%
CI
, 0.67–1.27;
P
=0.5) and 1‐year bleeding events (hazard ratio, 1.1; 95%
CI
, 0.4–2.3;
P
=0.8) did not differ.

Conclusions

These results from propensity score–matched registry data show that for elderly patients with
STEMI,
ticagrelor compared with clopidogrel was associated with a reduction in major adverse cardiac and cerebrovascular events without a significant increase in bleeding events within 1 year.
Effects of Hypothetical Interventions on Ischemic Stroke Using Parametric G-Formula
Authors: Mokhayeri Yaser , Hashemi-Nazari Seyed Saeed , Khodakarim Soheila , Safiri Saeid , Mansournia Nasrin , Mansournia Mohammad Ali , Kaufman Jay S. , Naimi Ashley I. 
Published: September 2019

Background and Purpose—
Standard analytic approaches (eg, logistic regression) fail to adequately control for time-dependent confounding and, therefore, may yield biased estimates of the total effect of the exposure on the outcome. In the present study, we estimate the effect of body mass index, intentional physical activity, HDL (high-density lipoprotein) cholesterol, LDL (low-density lipoprotein) cholesterol, hypertension, and cigarette smoking on the 11-year risk of ischemic stroke by sex using the parametric g-formula to control time-dependent confounders.

Methods—

Using data from the MESA (Multi-Ethnic Study of Atherosclerosis), we followed 6809 men and women aged 45 to 84 years. We estimated the risk of stroke under 6 hypothetical interventions: maintaining body mass index <25 kg/m
2
, maintaining normotension (systolic blood pressure <140 and diastolic <90 mm Hg), quitting smoking, maintaining HDL >1.55 mmol/L, maintaining LDL <3.11 mmol/L, and exercising at least 210 minutes per week. The effects of joint hypothetical interventions were also simulated.

Results—
In men, the 11-year risk of ischemic stroke would be reduced by 85% (95% CI, 66–96) for all 6 hypothetical interventions. In women, this same effect was estimated as 55% (95% CI, 6–82).

Conclusions—
The hypothetical interventions explored in our study resulted in risk reduction in both men and women.