bluuebunny/crossref_metadata_2025 huggingface dataset:
Determining best outcomes from community‐acquired pneumonia and how to achieve them
Authors: Hadfield Jane , Bennett Lesley
Published: November 2017

Community‐acquired pneumonia (CAP) is a common acute medical illness with a standard, effective treatment that was introduced before the evidenced‐based medicine era. Mortality rates have improved in recent decades but improvements have been minimal when compared to other conditions such as acute coronary syndromes. The standardized approach to treatment makes CAP a target for comparative performance and outcome measures. While easy to collect, simplistic outcomes such as mortality, readmission and length of stay are difficult to interpret as they can be affected by subjective choices and health care resources. Proposed clinical‐ and patient‐reported outcomes are discussed below and include measures such as the time to clinical stability (TTCS) and patient satisfaction, which can be compared between health institutions. Strategies to improve these outcomes include use of a risk stratification tool, local antimicrobial guidelines with antibiotic stewardship and care bundles to include early administration of antibiotics and early mobilization.
Endobronchial drug delivery: Expanding techniques and possibilities in interventional pulmonology
Authors: Steinfort Daniel P.
Published: November 2017

See related Article
Epidemiology and impact of bloodstream infections among kidney transplant recipients: A retrospective single‐center experience
Authors: Shendi Ali M. , Wallis Gabriel , Painter Helena , Harber Mark , Collier Sophie
Published: November 2017

Background

Bloodstream infection (BSI) represents an important source of morbidity and mortality, as well as an increasing therapeutic challenge, among solid organ transplant recipients. Understanding the epidemiological and microbiological characteristics of BSI following renal transplantation is paramount to the implementation of appropriate preventative and therapeutic measures.

Methods

We conducted a retrospective review of all BSI episodes occurring between July 2009 and April 2016 in adult patients, who received a renal transplant at Royal Free London hospital.

Results

A total of 116 episodes of BSI occurred in 87 patients, 43 (49.4%) of them men. The mean age at BSI was 54.37 ± 12.81 years. Late‐onset BSI (>12 months post transplant) represented 55.2%, with the median time to BSI being 16.28 month. Sixty‐seven patients had single BSI and 20 had recurrent episodes. Enterobacteriaceae were responsible for 73.7% of BSI, with Escherichia coli the commonest causative organism (46.6%). The urinary tract was the most frequent source of infection in 56.9%. Among the E. coli infections, 100% of the tested isolates were sensitive to meropenem, ertapenem, tigecycline, and fosfomycin, and >90% were sensitive to piperacillin‐tazobactam, amikacin, and colistin. Lower susceptibility rates were encountered for ceftriaxone (70.6%), amoxicillin‐clavulanic acid (48.1%), cotrimoxazole (40.4%), trimethoprim (37.3%), and amoxicillin (21.6%). During BSI, the median serum creatinine increased from a reference of 131 μmol/L to a peak of 219 μmol/L. Acute kidney injury (AKI) complicated 75/116 BSI episodes (64.7%)—stage 1: 34, stage 2: 31, and stage 3 AKI: 10 episodes. After 3 months, the median creatinine remained elevated at 146 μmol/L. The 3‐month mortality rate was 8% (7/87), and the death‐censored graft loss was 6.9% (6/87). No significant difference was seen between BSI of urinary and non‐urinary sources in the incidence of AKI (χ2 = 0.24, P = .6) or the percentage of creatinine change between baseline and peak and 3‐month creatinines (P = .2 and .7 respectively).

Conclusions

Urinary tract infection remains the commonest source of systemic infection among kidney transplant recipients and resistance to commonly used frontline antibiotics is common; thus, prevention and early detection are paramount. The appropriate choice of initial empirical antibiotic is vital to improve the outcome. Each unit needs to understand the epidemiology of organisms causing BSI in their transplant patients and their antibiotic susceptibilities.
Biomechanical properties of feline ventral abdominal wall and celiotomy closure techniques
Authors: Reina Rodriguez Fernando S. , Buckley Conor T. , Milgram Joshua , Kirby Barbara M.
Published: November 2017

Objective

To compare biomechanical properties and mechanism of failure of 3 regions of ventral abdominal wall in cats by using 2 suture materials, 2 suture bite‐to‐stitch intervals (SBSI), and full‐thickness versus fascia‐only closure.

Study Design

Randomized, cadaveric, ex vivo mechanical testing.

Sample Population

16 adult cat cadavers, 3 samples per cat.

Methods

Three regions of ventral abdominal wall were mechanically tested (N = 48 samples). Preumbilical, umbilical (U), and postumbilical (POU) regions were harvested by using a template. The thickness of the linea alba was recorded. Six samples without celiotomy served as controls. Twenty‐eight samples were randomized to SBSI (2 × 2 or 5 × 5 mm) and suture material (3‐0 polyglactin 910 or 3‐0 polydioxanone) for simple continuous celiotomy closure. Fourteen samples were randomized to full‐thickness or fascia‐only closure. Samples were tested by linear distraction; tensile strength and mechanism of failure were recorded. Effects of body weight, thickness of linea alba, anatomic region, SBSI, type of closure, and suture material were evaluated by mixed model linear analysis. Load to failure was compared between males and females, full‐thickness and fascia‐only closure by independent t test, with P < .05 considered statistically significant.

Results

The POU region achieved lower loads to failure. Load to failure was greater in males compared with females. No difference was detected between full‐thickness and fascia‐only closure. Failure most commonly occurred by tearing of suture through tissues. Tissue failure with suture line loosening occurred mainly in the 5 × 5‐mm SBSI group.

Conclusion

The POU region is biomechanically weak and may therefore be predisposed to incisional herniation.
Educating youth swine exhibitors on influenza A virus transmission at agricultural fairs
Authors: Nolting J. M. , Midla J. , Whittington M. S. , Scheer S. D. , Bowman A. S.
Published: November 2017

Influenza A virus (IAV) is a major zoonotic pathogen that threatens global public health. Novel strains of influenza A viruses pose a significant risk to public health due to their pandemic potential, and transmission of influenza A viruses from animals to humans is an important mechanism in the generation and introduction of IAVs that threaten human health. The purpose of this descriptive correlational study was to develop real‐life training scenarios to better inform swine exhibitors of the risks they may encounter when influenza A viruses are present in swine. Educational activities were implemented in five Ohio counties where exhibition swine had historically been shedding influenza A viruses during the county fair. A total of 146 youth swine exhibitors participated in the educational programme, and an increase in the knowledge base of these youth was documented. It is expected that educating youth exhibitors about exposure to influenza A virus infections in the swine they are exhibiting will result in altered behaviours and animal husbandry practices that will improve both human and animal health.
Measuring quantitative effects of methylation on transcription factor–DNA binding affinity
Authors: Zuo Zheng , Roy Basab , Chang Yiming Kenny , Granas David , Stormo Gary D.
Published: November 2017

We describe a new method for measuring the effects of epigenetic marks on protein-DNA interactions.
Two-dimensional limit of crystalline order in perovskite membrane films
Authors: Hong Seung Sae , Yu Jung Ho , Lu Di , Marshall Ann F. , Hikita Yasuyuki , Cui Yi , Hwang Harold Y.
Published: November 2017

A topological crystalline to amorphous phase transition predicted in 2D systems is observed in freestanding oxide films.
Tailor-made temperature-dependent thermal conductivity via interparticle constriction
Authors: Nutz Fabian A. , Retsch Markus
Published: November 2017

Mesostructuring and geometric constriction control the temperature-dependent thermal transport properties in granular matter.
Strained hybrid perovskite thin films and their impact on the intrinsic stability of perovskite solar cells
Authors: Zhao Jingjing , Deng Yehao , Wei Haotong , Zheng Xiaopeng , Yu Zhenhua , Shao Yuchuan , Shield Jeffrey E. , Huang Jinsong
Published: November 2017

Strain discovered in hybrid perovskite films made by existing methods affects perovskite solar cells’ intrinsic stability.
A PIP
2
-derived amplification loop fuels the sustained initiation of B cell activation
Authors: Xu Chenguang , Xie Hengyi , Guo Xingdong , Gong Haipeng , Liu Lei , Qi Hai , Xu Chenqi , Liu Wanli
Published: November 2017

A PIP
2
-derived amplification loop fuels the sustained initiation of B cell activation.
License to kill: IFN-λ regulates antifungal activity of neutrophils
Authors: Schnepf Daniel , Staeheli Peter
Published: November 2017

Interferon-λ mediates antifungal immunity by stimulating neutrophils to generate reactive oxygen species. See the related research article by

Espinosa
et al
.
Including children and young people in assessments: a practical guide
Authors: Green Lydia M C , Friend Amanda J , Bardgett Rebecca J M , Darling Jonathan C
Published: November 2017

The ability to interact with children and young people (CYP), appropriately examine and competently interpret signs is an essential skill for many medical practitioners and allied healthcare professionals; yet, how do we ensure competence in our students and trainees? One method is to include CYP in both formative and summative assessments; this provides an invaluable opportunity for examiners not only to evaluate the clinical interaction but also to gain an understanding of the CYP experience and what characteristics they value in a ‘good children’s doctor’. This paper explores the benefits and challenges of involving CYP in assessments and provides practical advice for course organisers, assessors and students when encountering CYP in assessment.
Interpretation of health news items reported with or without spin: protocol for a prospective meta-analysis of 16 randomised controlled trials
Authors: Haneef Romana , Yavchitz Amélie , Ravaud Philippe , Baron Gabriel , Oranksy Ivan , Schwitzer Gary , Boutron Isabelle
Published: November 2017

Introduction

We aim to compare the interpretation of health news items reported with or without spin. ‘Spin’ is defined as a misrepresentation of study results, regardless of motive (intentionally or unintentionally) that overemphasises the beneficial effects of the intervention and overstates safety compared with that shown by the results.

Methods and analysis

We have planned a series of 16 randomised controlled trials (RCTs) to perform a prospective meta-analysis. We will select a sample of health news items reporting the results of four types of study designs, evaluating the effect of pharmacological treatment and containing the highest amount of spin in the headline and text. News items reporting four types of studies will be included: (1) preclinical studies; (2) phase I/II (non-randomised) trials; (3) RCTs and (4) observational studies. We will rewrite the selected news items and remove the spin. The original news and rewritten news will be appraised by four types of populations: (1) French-speaking patients; (2) French-speaking general public; (3) English-speaking patients and (4) English-speaking general public. Each RCT will explore the interpretation of news items reporting one of the four study designs by each type of population and will include a sample size of 300 participants. The primary outcome will be participants’ interpretation of the benefit of treatment after reading the news items: (What do you think is the probability that treatment X would be beneficial to patients? (scale, 0 (very unlikely) to 10 (very likely)).

This study will evaluate the impact of spin on the interpretation of health news reporting results of studies by patients and the general public.

Ethics and dissemination

This study has obtained ethics approval from the Institutional Review Board of the Institut national de la santé et de la recherche médicale (INSERM) (registration no: IRB00003888). The description of all the steps and the results of this prospective meta-analysis will be available online and will be disseminated as a published article. On the completion of this study, the results will be sent to all participants.

PROSPERO registration number

CRD42017058941.
Early vasopressor use following traumatic injury: a systematic review
Authors: Hylands Mathieu , Toma Augustin , Beaudoin Nicolas , Frenette Anne Julie , D’Aragon Frédérick , Belley-Côté Émilie , Charbonney Emmanuel , Møller Morten Hylander , Laake Jon Henrik , Vandvik Per Olav , Siemieniuk Reed Alexander , Rochwerg Bram , Lauzier François , Green Robert S , Ball Ian , Scales Damon , Murthy Srinivas , Kwong Joey S W , Guyatt Gordon , Rizoli Sandro , Asfar Pierre , Lamontagne François
Published: November 2017

Objectives

Current guidelines suggest limiting the use of vasopressors following traumatic injury; however, wide variations in practice exist. Although excessive vasoconstriction may be harmful, these agents may help reduce administration of potentially harmful resuscitation fluids. This systematic review aims to compare early vasopressor use to standard resuscitation in adults with trauma-induced shock.

Design

Systematic review.

Data sources

We searched MEDLINE, EMBASE, ClinicalTrials.gov and the Central Register of Controlled Trials from inception until October 2016, as well as the proceedings of 10 relevant international conferences from 2005 to 2016.

Eligibility criteria for selecting studies

Randomised controlled trials and controlled observational studies that compared the early vasopressor use with standard resuscitation in adults with acute traumatic injury.

Results

Of 8001 citations, we retrieved 18 full-text articles and included 6 studies (1 randomised controlled trial and 5 observational studies), including 2 published exclusively in abstract form. Across observational studies, vasopressor use was associated with increased short-term mortality, with unadjusted risk ratios ranging from 2.31 to 7.39. However, the risk of bias was considered high in these observational studies because patients who received vasopressors were systematically sicker than patients treated without vasopressors. One clinical trial (n=78) was too imprecise to yield meaningful results. Two clinical trials are currently ongoing. No study measured long-term quality of life or cognitive function.

Conclusions

Existing data on the effects of vasopressors following traumatic injury are of very low quality according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. With emerging evidence of harm associated with aggressive fluid resuscitation and, in selected subgroups of patients, with permissive hypotension, the alternatives to vasopressor therapy are limited. Observational data showing that vasopressors are part of usual care would provide a strong justification for high-quality clinical trials of early vasopressor use during trauma resuscitation.

Trial registration number

CRD42016033437.
Contribution of short sleep duration to ethnic differences in cardiovascular disease: results from a cohort study in the Netherlands
Authors: Anujuo Kenneth , Agyemang Charles , Snijder Marieke B , Jean-Louis Girardin , Born Bert-Jan van den , Peters Ron J G , Stronks Karien
Published: November 2017

Objectives

We analysed association between short sleep duration and prevalence of cardiovascular disease (CVD) in a multiethnic population living in the Netherlands, and the contribution of short sleep to the observed ethnic differences in the prevalence of CVD, independent of CVD risk factors.

Methods

20 730 participants (aged 18–71 years) of the HELIUS (Healthy Life in an Urban Setting) Study were investigated. Self-reported sleep duration was classified as: short (<7 hours/night) and healthy (7–9 hours/night). Prevalence of CVD was assessed using the Rose Questionnaire on angina pectoris, intermittent claudication and possible myocardial infarction. Association of short sleep duration with prevalent CVD and the contribution of short sleep to the observed ethnic differences in the prevalence of CVD were analysed using adjusted prevalence ratio(s) (PRs) with 95% CI.

Results

Results indicate that short sleep was associated with CVD among all ethnic groups with PRs ranging from 1.41 (95% CI 1.21 to 1.65) in Moroccans to 1.62 (95% CI 1.20 to 2.18) in Dutch after adjustment for age, sex and conventional CVD risk factors. The independent contributions of short sleep (in percentage) to ethnic differences in CVD compared with Dutch were 10%, 15%, 15%, 5% and 5% in South-Asian Surinamese, African-Surinamese, Ghanaian, Turkish and Moroccan, respectively.

Conclusion

Short sleep contributed to ethnic differences in CVD independent of well-known CVD risk factors particularly in Surinamese and Ghanaian groups. Reducing sleep deprivation may be a relevant entry point for reducing increased CVD risks among the various ethnic minority groups.
Physical activity in former elite cricketers and strategies for promoting physical activity after retirement from cricket: a qualitative study
Authors: Filbay Stephanie R , Bishop Felicity L , Peirce Nicholas , Jones Mary E , Arden Nigel K
Published: November 2017

Objectives

The health benefits of professional sport dissipate after retirement unless an active lifestyle is adopted, yet reasons for adopting an active or inactive lifestyle after retirement from sport are poorly understood. Elite cricket is all-encompassing, requiring a high volume of activity and unique physical demands. We aimed to identify influences on physical activity behaviours in active and insufficiently active former elite cricketers and provide practical strategies for promoting physical activity after cricket retirement.

Design

18 audio-recorded semistructured telephone interviews were performed. An inductive thematic approach was used and coding was iterative and data-driven facilitated by NVivo software. Themes were compared between sufficiently active and insufficiently active participants.

Setting

All participants formerly played professional cricket in the UK.

Participants

Participants were male, mean age 57±11 (range 34–77) years, participated in professional cricket for 12±7 seasons and retired on average 23±9 years previously. Ten participants (56%) were classified as sufficiently active according to the UK Physical Activity Guidelines (moderate-intensity activity ≥150 min per week or vigorous-intensity activity ≥75 min per week). Eight participants did not meet these guidelines and were classified as insufficiently active.

Results

Key physical activity influences were time constraints, habit formation, intrinsic and extrinsic motivation, physical activity preferences, pain/physical impairment and cricket coaching. Recommendations for optimising physical activity across the lifespan after cricket retirement included; prioritise physical activity, establish a physical activity plan prior to cricket retirement and don’t take a break from physical activity, evaluate sources of physical activity motivation and incorporate into a physical activity plan, find multiple forms of satisfying physical activity that can be adapted to accommodate fluctuations in physical capabilities across the lifespan and coach cricket.

Conclusions

Physically active and less active retired cricketers shared contrasting attributes that informed recommendations for promoting a sustainable, physically active lifestyle after retirement from professional cricket.
SubclinicalPropionibacterium acnesinfection estimation in the intervertebral disc (SPInE-ID): protocol for a prospective cohort
Authors: Astur Nelson , Martins Delio E , Wajchenberg Marcelo , Ferretti Mario , Menezes Fernando G , Doi Andre M , Rosemberg Laercio A , Santos Durval C B , Iutaka Alexandre S , Rodrigues Luciano M R , Martino Marines D V , Pagura Jorge R , Kihara Filho Eduardo N , Lenza Mario
Published: November 2017

Introduction

Low back pain and vertebral endplate abnormalities are common conditions within the population. Subclinical infection caused by indolent pathogens can potentially lead to these findings, with differentiation between them notably challenging from a clinical perspective. Progressive infection of the intervertebral disc has been extensively associated with increasing low back pain, withPropionibacterium acnesspecifically implicated with in relation to sciatica. The main purpose of this study is to identify if the presence of an infective pathogen within the intervertebral disc is primary or is a result of intraoperative contamination, and whether this correlates to low back pain.

Methods and analysis

An open prospective cohort study will be performed. Subjects included within the study will be between the ages of 18 and 65 years and have a diagnosis of lumbar disc herniation requiring open decompression surgery. Excised herniated disc fragments, muscle and ligamentum flavum samples will be collected during surgery and sent to microbiology for tissue culture and pathogen identification. Score questionnaires for pain, functionality and quality of life will be given preoperatively and at 1, 3, 6 and 12 months postoperatively. A MRI will be performed 12 months after surgery for analysis of Modic changes and baseline comparison. The primary endpoint is the rate of disc infection in patients with symptomatic degenerative disc disease. The secondary endpoints will be performance scores, Modic incidence and volume.

Ethics and dissemination

This study was approved by our Institutional Review Board and was only initiated after it (CAAE 65102617.2.0000.0071). Patients agreeing to participate will sign an informed consent form before entering the study. Results will be published in a peer reviewed medical journal irrespective of study findings. If shown to be the case, this would have profound effects on the way physicians treat chronic low back pain, even impacting health costs.

Trials registration number

NCT0315876; Pre-results.
Protocol of the sepsivit study: a prospective observational study to determine whether continuous heart rate variability measurement during the first 48 hours of hospitalisation provides an early warning for deterioration in patients presenting with infection or sepsis to the emergency department of a Dutch academic teaching hospital
Authors: Quinten Vincent M , van Meurs Matijs , Renes Maurits H , Ligtenberg Jack J M , ter Maaten Jan C
Published: November 2017

Introduction

One in five patients with sepsis deteriorates within 48 hours after hospital admission. Regrettably, a clear tool for the early detection of deterioration is still lacking. The SepsiVit study aims to determine whether continuous heart rate variability (HRV) measurement can provide an early warning for deterioration in patients presenting with suspected infection or sepsis to the emergency department (ED).

Methods and analysis

The protocol of a prospective observational study in the ED. We will include 171 adult medical patients presenting with suspected infection or sepsis and at least two systemic inflammatory response syndrome criteria. Patients with known pregnancy, cardiac transplantation or not admitted to our hospital are excluded.

High sample frequency ECG signals (500 Hz), respiratory rate, blood pressure and peripheral oxygen saturation will be recorded continuously during the first 48 hours of hospitalisation using a bedside patient monitor (Philips IntelliVue MP70). Primary endpoint is patient deterioration, defined as the development of organ dysfunction, unplanned intensive care unit admission or in-hospital mortality. The ECG data will be used for offline HRV analysis. We will compare the HRV between two groups (deterioration/no deterioration) and analyse whether HRV provides an early warning for deterioration. Furthermore, we will create a multivariate predictive model for deterioration based on heart rate, respiratory rate and HRV. As planned secondary analyses, we (1) perform a subgroup analysis for patients with pneumosepsis and urosepsis and (2) determine whether HRV using lower sample frequencies (1 Hz or less) suffices to predict deterioration.

Ethics and dissemination

The Institutional Review Board of the University Medical Center Groningen granted a waiver for the study (METc 2015/164). Results will be disseminated through international peer-reviewed publications and conference presentations. A lay summary of the results will be provided to the study participants.

Trial registration number

NTR6168; Pre-results.
Effect of ephedrine and phenylephrine on brain oxygenation and microcirculation in anaesthetised patients with cerebral tumours: study protocol for a randomised controlled trial
Authors: Koch Klaus Ulrik , Tietze Anna , Aanerud Joel , Öettingen Gorm von , Juul Niels , Sørensen Jens Christian Hedemann , Nikolajsen Lone , Østergaard Leif , Rasmussen Mads
Published: November 2017

Introduction

During brain tumour surgery, vasopressor drugs are commonly administered to increase mean arterial blood pressure with the aim of maintaining sufficient cerebral perfusion pressure. Studies of the commonly used vasopressors show that brain oxygen saturation is reduced after phenylephrine administration, but unaltered by ephedrine administration. These findings may be explained by different effects of phenylephrine and ephedrine on the cerebral microcirculation, in particular the capillary transit-time heterogeneity, which determines oxygen extraction efficacy. We hypothesised that phenylephrine is associated with an increase in capillary transit-time heterogeneity and a reduction in cerebral metabolic rate of oxygen compared with ephedrine. Using MRI and positron emission tomography (PET) as measurements in anaesthetised patients with brain tumours, this study will examine whether phenylephrine administration elevates capillary transit-time heterogeneity more than ephedrine, thereby reducing brain oxygenation.

Methods and analysis

This is a double-blind, randomised clinical trial including 48 patients scheduled for surgical brain tumour removal. Prior to imaging and surgery, anaesthetised patients will be randomised to receive either phenylephrine or ephedrine infusion until mean arterial blood pressure increases to above 60 mm Hg or 20% above baseline. Twenty-four patients were allocated to MRI and another 24 patients to PET examination. MRI measurements include cerebral blood flow, capillary transit-time heterogeneity, cerebral blood volume, blood mean transit time, and calculated oxygen extraction fraction and cerebral metabolic rate of oxygen for negligible tissue oxygen extraction. PET measurements include cerebral metabolic rate of oxygen, cerebral blood flow and oxygen extraction fraction. Surgery is initiated after MRI/PET measurements and subdural intracranial pressure is measured.

Ethics and dissemination

This study was approved by the Central Denmark Region Committee on Health Research Ethics (12 June 2015; 1-10-72-116-15). Results will be disseminated via peer-reviewed publication and presentation at international conferences.

Trial registration number

NCT02713087; Pre-results. 2015-001359-60; Pre-results.
Fixation stability of the upward gaze in patients with myasthenia gravis: an eye-tracker study
Authors: Mihara Miharu , Hayashi Atsushi , Fujita Kazuya , Kakeue Ken , Tamura Ryoi
Published: November 2017

Objective

To quantify fixation stability of the upward gaze in patients with myasthenia gravis (MG) using an eye tracker.

Methods and analysis

In this study, 21 normal subjects, 5 patients with MG with diplopia, 5 patients with MG without diplopia and 6 patients with superior oblique (SO) palsy were included. Subjects fixated on a target in the upward direction for 1 min. The horizontal (X) and vertical (Y) eye positions were recorded using an eye tracker. Fixation stability was first quantified using the bivariate contour ellipse areas (BCEA) of fixation points as an index of whole stability. Then, the SDs of the X and Y eye positions (SDX and SDY, respectively) were quantified as indices of directional stability, with the data divided into three 20 s fractions to detect temporal fixation fluctuation.

Results

BCEAs were larger in patients with MG (both with and without diplopia) than normal subjects and patients with SO palsy, without significant differences among the three 20 s fractions. Compared with normal subjects, SDXs were larger only in patients with MG with diplopia; SDYs were larger in both patients with MG with and without diplopia. In addition, SDYs in patients with MG with diplopia were larger than those in patients with MG without diplopia and patients with SO palsy. Furthermore, a significant difference among the three 20 s fractions was detected for SDYs in patients with MG with diplopia.

Conclusion

Patients with MG, especially those with diplopia, exhibit fixation instability in the upward gaze. Non-invasive quantification of fixation stability with an eye tracker is useful for precisely identifying MG-specific fatigue characteristics.

Trial registration number

UMIN000023468; pre-results.
Neither non-toxigenicStaphylococcus aureusnor commensalS.epidermidiactivates NLRP3 inflammasomes in human conjunctival goblet cells
Authors: Li Dayu , Hodges Robin R , Bispo Paulo , Gilmore Michael S , Gregory-Ksander Meredith , Dartt Darlene A
Published: November 2017

Purpose

The conjunctiva is a wet mucosal surface surrounding the cornea that is continuously exposed to pathogens. Nevertheless, persistent inflammation is not observed. We examined if the NOD-like receptor pyrin domain 3 (NLRP3) inflammasome functions as a sensor that distinguishes commensal and non-pathogenic bacteria from pathogenic bacteria in human conjunctival goblet cells.

Methods

Goblet cells were grown from human conjunctiva and co-cultured with commensalStaphylococcus epidermidis, isogenic non-toxigenicS. aureusACL135 and as a control toxigenicS. aureusRN6390. Activation of the NLRP3 inflammasome was determined by measuring changes in NF-κB activity, expression of pro-interleukin (IL)-1β and NLRP3, activation of caspase-1 and secretion of mature IL-1β. Goblet cell mucin secretion was measured in parallel.

Results

While all three strains of bacteria were able to bind to goblet cells, neither commensalS. epidermidisnor isogenic non-toxigenicS. aureusACL135 was able to stimulate an increase in (1) NF-κB activity, (2) pro-IL-1β and NLRP3 expression, (3) caspase-1 activation, (4) mature IL-1β and (5) mucin secretion. ToxigenicS. aureus,the positive control, increased these values: knockdown of NLRP3 with small interfering RNA (siRNA) completely abolished the toxigenicS. aureus-induced expression of pro-IL-1β and secretion of mature IL-1β.

Conclusions

We conclude that NLRP3 serves as a sensor capable of discriminating commensal and non-pathogenic bacteria from pathogenic bacteria in conjunctival goblet cells, and that activation of the NLRP3 inflammasome induced by pathogenic bacteria mediates secretion of both mature IL-1β and large secretory mucins from these cells.
Mortality among referrals to a community-based intermediate care team
Authors: Lakkappa Bharath , Shah Sanjay , Rogers Stephen , Holman Leanne Helen
Published: November 2017

Objectives

Intermediate care services have been introduced to help mitigate unnecessary hospital demand and premature placement in long-term residential care. Many patients are elderly and/or with complex comorbidities, but little consideration has been given to the palliative care needs of patients referred to intermediate care services. The objective of this study is to determine the proportion of patients referred to a community-based intermediate care team who died during care and up to 24 months after discharge and so to help inform the development of supportive and palliative care in this setting.

Methods

A retrospective cohort study of all 4770 adult patients referred to Northamptonshire Intermediate Care Team (ICT) between 11 April 2010 and 10 April 2011.

Results

Of 4770 patients referred, 60% were 75 years or older and 32% were 85 years of age or older. 4.0% of patients died during their ICT stay and 11% within 30 days of discharge. At the end of 12 months, 25% of the patients had died, increasing to 32% before the end of the second year. About 34% of all deaths occurred during the ICT stay or within 30 days of discharge, and a further 46% by the end of the first year. Male gender and higher age were associated with greater likelihood of death.

Conclusions

It is important for ICT clinicians to consider immediate and longer-term palliative care needs among patients referred to ICTs. Care models involving ICTs and palliative care teams working together could enable more people with end-stage non-cancer illnesses to die at home.
Addressing decisional conflict about fertility preservation: helping young female cancer survivors’ family planning decisions
Authors: Müller Madleina , Urech Corinne , Boivin Jacky , Ehrbar Verena , Moffat Rebecca , Daellenbach Rosanna Zanetti , Rochlitz Christoph , Tschudin Sibil
Published: November 2017

Background

Health professionals are challenged by a growing number of young long-term cancer survivors with their specific needs with regard to family planning. This study aimed at assessing decisional conflict (DC) in young female cancer patients regarding fertility preservation, identifying demographic, fertility and fertility preservation related factors, which may affect DC, and assessing the helpfulness of various decision-supports.

Methods

A retrospective, cross-sectional, web-based survey via an online questionnaire available in three languages with specific items concerning cancer, fertility, fertility preservation and the validated Decisional Conflict Scale targeted at current or former female cancer patients aged 18–45 years, with cancer types or treatment potentially affecting reproductive function.

Results

The 155 participating women showed considerable DC, especially with regard to missing information and support. DC was significantly lower in patients when the risk of infertility was discussed with a health professional, when they had undergone any procedure to preserve fertility, and when they had a university education. A longer time interval since cancer diagnosis was associated with higher DC. The most helpful decision-support tools were specialised websites and leaflets.

Conclusions

Young female cancer patients’ DC with regard to fertility preservation is very high. Information and support seem to be deficient. More information through standardised information tools might be an effective strategy to lower their DC at the time when treatment decisions need to be taken, and to improve their reproductive health after they have overcome cancer in the future.
Genome-wide association study of telomere length among South Asians identifies a second RTEL1 association signal
Authors: Delgado Dayana A , Zhang Chenan , Chen Lin S , Gao Jianjun , Roy Shantanu , Shinkle Justin , Sabarinathan Mekala , Argos Maria , Tong Lin , Ahmed Alauddin , Islam Tariqul , Rakibuz-Zaman Muhammad , Sarwar Golam , Shahriar Hasan , Rahman Mahfuzar , Yunus Mohammad , Jasmine Farzana , Kibriya Muhammad G , Ahsan Habibul , Pierce Brandon L
Published: November 2017

Background

Leucocyte telomere length (TL) is a potential biomarker of ageing and risk for age-related disease. Leucocyte TL is heritable and shows substantial differences by race/ethnicity. Recent genome-wide association studies (GWAS) report ~10 loci harbouring SNPs associated with leucocyte TL, but these studies focus primarily on populations of European ancestry.

Objective

This study aims to enhance our understanding of genetic determinants of TL across populations.

Methods

We performed a GWAS of TL using data on 5075 Bangladeshi adults. We measured TL using one of two technologies (qPCR or a Luminex-based method) and used standardised variables as TL phenotypes.

Results

Our results replicate previously reported associations in the TERC and TERT regions (P=2.2×10−8 and P=6.4×10−6, respectively). We observed a novel association signal in the RTEL1 gene (intronic SNP rs2297439; P=2.82×10−7) that is independent of previously reported TL-associated SNPs in this region. The minor allele for rs2297439 is common in South Asian populations (≥0.25) but at lower frequencies in other populations (eg, 0.07 in Northern Europeans). Among the eight other previously reported association signals, all were directionally consistent with our study, but only rs8105767 (ZNF208) was nominally significant (P=0.003). SNP-based heritability estimates were as high as 44% when analysing close relatives but much lower when analysing distant relatives only.

Conclusions

In this first GWAS of TL in a South Asian population, we replicate some, but not all, of the loci reported in prior GWAS of individuals of European ancestry, and we identify a novel second association signal at the RTEL1 locus.
Genetics of Parkinson’s disease and related disorders
Authors: Zhang Pei-Lan , Chen Yan , Zhang Chen-Hao , Wang Yu-Xin , Fernandez-Funez Pedro
Published: November 2017

Parkinson’s disease (PD) is a complex and heterogeneous neurological condition characterised mainly by bradykinesia, resting tremor, rigidity and postural instability, symptoms that together comprise the parkinsonian syndrome. Non-motor symptoms preceding and following clinical onset are also helpful diagnostic markers revealing a widespread and progressive pathology. Many other neurological conditions also include parkinsonism as primary or secondary symptom, confounding their diagnosis and treatment. Although overall disease course and end-stage pathological examination single out these conditions, the significant overlaps suggest that they are part of a continuous disease spectrum. Recent genetic discoveries support this idea because mutations in a few genes (α-synuclein, LRRK2, tau) can cause partially overlapping pathologies. Additionally, mutations in causative genes and environmental toxins identify protein homeostasis and the mitochondria as key mediators of degeneration of dopaminergic circuits in the basal ganglia. The evolving mechanistic insight into the pathophysiology of PD and related conditions will contribute to the development of targeted and effective symptomatic treatments into disease-modifying therapies that will reduce the burden of these dreadful conditions.
Review of determinants of national medical leadership development
Authors: Keijser Wouter , Poorthuis Max , Tweedie Judith , Wilderom Celeste
Published: November 2017

Increasingly, physician engagement in management, quality and innovation is being recognised as vital, requiring ‘medical leadership’ (ML) competencies. Besides numerous local institutional efforts and despite the high level of autonomy of the medical profession and the education of its members, in some countries, national level activities are focusing on developing ML competencies to guide physicians in more effectively engaging in these non-medical activities. Up to this date, little is known about effective strategies and tactics for developing ML on a national level. This study investigates existing literature on determinants and interventions for national ML development. We performed a scoping review and subsequent systematic literature review of published reviews, using PubMed, Scopus, Web of Science, Ovid MEDLINE and Science Direct in search for eligible papers between 2011 and 2016. Full-text versions of 43 papers were studied, and a snowballing method was deployed. Data extraction included grounded theory coding, and synthesis of data was done iteratively during data clinics. Analysis of the seven included papers resulted in five discrete categories of determinants of and 10 distinct interventions relevant to national development of ML approaches. None of the papers reported on any specific phasing of national ML development. Our data suggest that local and national level activities in ML development should consider multifaceted and multilevel approaches, taking into account resistance to change and redesign of institutionalised logics that accompany changing positions and reconstruction of professional identities of physicians.
Nudging, informed consent and bullshit
Authors: Simkulet William
Published: November 2017

Some philosophers have argued that during the process of obtaining informed consent, physicians should try to nudge their patients towards consenting to the option the physician believes best, where a nudge is any influence that is expected to predictably alter a person’s behaviour without (substantively) restricting her options. Some proponents of nudging even argue that it is a necessary and unavoidable part of securing informed consent. Here I argue that nudging is incompatible with obtaining informed consent. I assume informed consent requires that a physician tells her patient the truth about her options and argue that nudging is incompatible with truth-telling. Instead, nudging satisfies Harry Frankfurt’s account of bullshit.
Assessment of thrombus length in acute ischemic stroke by post-contrast magnetic resonance angiography
Authors: Ganeshan Ramanan , Nave Alexander H , Scheitz Jan F , Schindlbeck Katharina A , Haeusler Karl Georg , Nolte Christian H , Villringer Kersten , Fiebach Jochen B
Published: November 2017

Objectives

Post-contrast magnetic resonance angiography (PC-MRA) enables visualization of vessel segments distal to an intra-arterial thrombus in acute ischemic stroke. We hypothesized that PC-MRA also allows clot length measurement in different intracranial vessels.

Methods

Patients with MRI-confirmed ischemic stroke and intracranial artery occlusion within 24 hours of symptom onset were prospectively evaluated. PC-MRA was added to a standard stroke MRI protocol. Thrombus length was measured on thick slab maximum intensity projection images. Clinical outcome at hospital discharge was assessed by modified Rankin Scale (mRS).

Results

Thirty-four patients (median age 72 years) presenting with a median National Institutes of Health Stroke Scale score of 11 and a median onset to imaging time of 116 min were included. PC-MRA enabled precise depiction of proximal and distal terminus of the thrombus in 31 patients (91%), whereas in three patients (9%) PC-MRA presented a partial occlusion. Median thrombus length in patients with complete occlusion was 9.9 mm. In patients with poor outcome (mRS ≥3) median thrombus length was significantly longer than in those with good outcome (mRS ≤2;P=0.011).

Conclusions

PC-MRA demonstrates intra-arterial thrombus length at different vessel occlusion sites. Longer thrombus length is associated with poor clinical outcome.

Clinical trial registration

NCT02077582; Results.
Unusual clinical presentation of cryptococcosis in an immunocompetent cat
Authors: Sanchini Lucia , Reading Mark , Williams Tim , Archer Joy
Published: November 2017

This case report describes an atypical presentation of cryptococcal infection in a cat initially presented with multiple persistent pruritic exudative skin lesions, which did not subside following administration of antibiotics and corticosteroids. Both fungal culture and feline immunodeficiency virus (FIV)/feline leukaemia virus (FeLV) ELISA test yielded negative results. Cytological examination of the skin scrapings was consistent with infection by Cryptococcus, which was confirmed by both postmortem inspection and histopathological examination of the lesions. The observed multifocal skin lesions are the result of haematogenous dissemination of the yeast, which is generally seen in immunocompromised cats. Clinical signs of systemic infection by Cryptococcus include apathy and cachexia and may or may not follow classical nasal disease. Surprisingly, the cat described in this report was immunocompetent, presented in good general condition and with no nasal discharge.
Emphysematous gastritis associated with Clostridium perfringens type A in a cat
Authors: Burn Jessica , Rousset Nicolas , Henderson Debra W , Legge Carolyn , Uzal Francisco A
Published: November 2017

A ten‐year‐old male neutered Maine Coon cat was presented with lethargy, weakness, dehydration and inappetence of 48 hours' duration. Initial ultrasound revealed gastric distension, a normal gastric wall and segmental circumferential thickening of the jejunum wall. The cat initially improved with supportive care, but deteriorated on the second day of hospitalisation. Repeat ultrasound examination and radiography 24 hours after presentation showed marked gastric wall thickening with emphysematous changes. At gastroscopy, severe gastric mucosal discoloration was seen, suggestive of necrosis. Euthanasia was performed post‐gastroscopy due to the deteriorating clinical signs and a suspicion of generalised gastric wall necrosis. Postmortem examination and results of ancillary tests confirmed moderate necrosuppurative and emphysematous gastritis, and focal, mild, necrosuppurative and emphysematous enteritis associated with Clostridium perfringens type A infection. C perfringens infection is rare in small animals; however, it can cause severe and sometimes fatal gastrointestinal disease if the bacteria invade and colonise the gastrointestinal wall.
Repetitive vegetative propagation of first-year sea buckthorn (Hippophae rhamnoides L.) cuttings
Authors: Dale Adam , Galić Dragan
Published: November 2017

Sea buckthorn (Hippophae rhamnoides L.) is used in beverages, pharmaceuticals, cosmetic products, and animal feeds. Although sea buckthorn has been shown to be easy to propagate vegetatively, currently, there is little information on reliable techniques to vegetatively propagate the plant repetitively within a single year. To address this, three experiments were conducted to study whether season and chilling affected the successful rooting of cuttings. Four cultivars, ‘Chuskaya’, ‘Golden Rain’, ‘Lord’, and ‘Sunny’, were used in the season- and chilling-effect experiments. Hardwood and softwood cuttings from field-grown plants did not root from October to December. The percent of rooted cuttings in January was cultivar-dependent. The number and percent of rooted greenhouse-produced cuttings were significantly affected by length of chilling. Most cuttings were produced and the highest percent rooted when the plants chilled for at least 6 wk. ‘Lord’ had the most and ‘Golden Rain’ the least number of rooted cuttings. This study indicated that greenhouse-grown stock plants were a viable source of sea buckthorn cuttings for vegetative propagation. When combined with field-grown sources, it is possible to produce sea buckthorn planting material year-round.