bluuebunny/crossref_metadata_2025 huggingface dataset:
Dofetilide for suppression of atrial fibrillation in hypertrophic cardiomyopathy: A case series and literature review
Authors: Moore JoEllyn C. , Trager Lena , Anzia Lucille E. , Saliba Walid , Bassiouny Mohamed , Bhargava Mandeep , Chung Mina , Desai Milind , Garberich Ross , Lever Harry , Lindsay Bruce D. , Sengupta Jay , Tchou Patrick , Wazni Oussama , Wilkoff Bruce L.
Published: February 2018

Background

Limited medical options are available for rhythm control in patients with atrial fibrillation (AF) and hypertrophic cardiomyopathy (HCM). There are no published reports of dofetilide use in this population.

Methods

A retrospective chart review was conducted on 1,404 patients loaded on dofetilide for AF suppression at the Cleveland Clinic from 2008 to 2012, 25 of whom were found to have HCM.

Results

The HCM cohort was 32% female, 76% with persistent AF, mean age of 59 ± 10 years, and mean ejection fraction of 54 ± 9 %. Of the 25 patients, 21 were discharged on dofetilide, three discontinued during loading due to QTc prolongation, and one due to inefficacy. There were no adverse events during loading. Of those discharged on dofetilide, 11/21 (52%) were still on it at a median follow‐up of 396 (198, 699) days at the time of the chart review. For those in whom it was discontinued, the median time on the drug was 301 (111, 738) days. Of the 10 patients who discontinued dofetilide during follow‐up, six were due to inefficacy, one postablation, one postheart transplant, one due to death secondary to lung cancer, and one due to worsening edema.

Conclusions

Dofetilide was well tolerated in this group of patients with AF and HCM and it facilitated management of AF in 21/25 (84%) patients. Further research is needed to assess the safety and efficacy of dofetilide in order to develop evidence‐based guidelines for the pharmacological management of AF in this population.
Olive (Olea europaea) leaf extract alters the cytokine profile of Leishmania major‐infected macrophages: New insight into the underlying mechanism
Authors: Kheirandish F. , Mosaffa N. , Tarahi M. J. , Fallahi Sh.
Published: February 2018

This study aimed to identify the effects of olive leaf extract (OLE) on IFNγ, TNFα, TGFβ and nitric oxide (NO) resulted from macrophages infected with Leishmania major (L. major) amastigotes in the culture medium. High‐performance liquid chromatography (HPLC) was used to analyse the level of Oleuropein in plant extract. To evaluate the immunomodulatory effects of OLE, the isolated BALB/c mice peritoneal macrophages were infected with L. major promastigotes and treated with 6.25, 12.5 and 25 μg/mL concentrations of OLE. To assess the cytokines, supernatants of cell cultures were harvested after 12, 24 and 48 hours. Cytokine production was evaluated by ELISA. Nitrite accumulation in the culture medium was assessed using the Griess reaction. The level of Oleuropein in the extract was 18.45% by HPLC. According to results, the production of IFNγ and TNFα was significantly increased when the infected and/or not infected macrophages with L. major promastigotes were affected by different concentrations of OLE. Conversely, the production of TGFβ was significantly decreased under the same conditions. Furthermore, the colorimetric determination of NO accumulation in the culture medium indicated that OLE has no effect on NO production. The study corroborates the immunomodulatory effects of OLE on L. major‐infected macrophages.
Transcription factors PRE3 and WOX11 are involved in the formation of new lateral roots from secondary growth taproot in A. thaliana
Authors: Baesso B. , Chiatante D. , Terzaghi M. , Zenga D. , Nieminen K. , Mahonen A.P. , Siligato R. , Helariutta Y. , Scippa G.S. , Montagnoli A.
Published: February 2018

The spatial deployment of lateral roots determines the ability of a plant to interact with the surrounding environment for nutrition and anchorage. This paper shows that besides the pericycle, the vascular cambium becomes active in Arabidopsis thaliana taproot at a later stage of development and is also able to form new lateral roots.

To demonstrate the above, we implemented a two‐step approach in which the first step leads to development of a secondary structure in A. thaliana taproot, and the second applies a mechanical stress on the vascular cambium to initiate formation of a new lateral root primordium.

GUS staining showed PRE3, DR5 and WOX11 signals in the cambial zone of the root during new lateral root formation. An advanced level of wood formation, characterized by the presence of medullar rays, was achieved.

Preliminary investigations suggest the involvement of auxin and two transcription factors (PRE3/ATBS1/bHLH135/TMO7 and WOX11) in the transition of some vascular cambium initials from a role as producers of xylem/phloem mother cells to founder cells of a new lateral root primordium.
Studies on lead and cadmium toxicity in Dianthus carthusianorum calamine ecotype cultivated in vitro
Authors: Muszyńska E. , Hanus‐Fajerska E. , Ciarkowska K.
Published: February 2018

Information on metallophytes during reclamation of land contaminated with heavy metals is sparse. We investigated the response of D. carthusianorum calamine ecotype to Pb and Cd stress. We focused on in vitro selection of tolerant plant material for direct use in chemically degraded areas.

Shoot cultures were treated with various concentrations of Pb or Cd ions. Plantlet status was estimated as micropropagation efficiency, growth tolerance index (GTI) and through physiological analysis. Moreover, determination of plant Pb, Cd and other elements was performed.

The application of Pb(NO3)2 resulted in stronger growth inhibition than application of CdCl2. In the presence of Pb ions, a reduction was observed of both, the micropropagation coefficient to 1.1–1.8 and the GTI to 48%. In contrast, Cd ions had a positive influence on tested cultures, expressed as an increase of GTI up to 243% on medium enriched with 1.0 μm CdCl2. Moreover, photosynthetic pigment content in shoots cultivated on media with CdCl2 was higher than in control treatment. The adaptation to Cd was associated with decreased accumulation of phenols in the order: 0.0 μm > 1.0 μm > 3.0 μm > 5.5 μm CdCl2. It seems that high tolerance to Cd is related to K uptake, which is involved in antioxidant defence.

This work presents an innovative approach to the impact of Cd ions on plant growth and suggests a potential biological role of this metal in species from metalliferous areas.
Reports from the Field: Earned Local Media in Presidential Campaigns
Authors: Darr Joshua P.
Published: February 2018

Presidential campaigns that understand the behaviors and interests of media organizations are rewarded with increased exposure in the news. Campaigns attract attention from local media by appealing to the news values of proximity and conflict. I compare campaign coverage in areas with and without a local campaign presence using an original, nationwide data set from three recent U.S. presidential elections and find that candidates receive more stories in the local press in areas where they establish a presence. By subsidizing locally framed content, campaigns can increase their local earned media, with larger effects in competitive states and areas without investments in previous elections.
gBOIN: A Unified Model-Assisted Phase I Trial Design Accounting for Toxicity Grades, and Binary or Continuous End Points
Authors: Mu Rongji , Yuan Ying , Xu Jin , Mandrekar Sumithra J. , Yin Jun
Published: February 2018

The landscape of oncology drug development has recently changed with the emergence of molecularly targeted agents and immunotherapies. These new therapeutic agents appear more likely to induce multiple low or moderate grade toxicities rather than dose limiting toxicities. Various model-based dose finding designs and toxicity severity scoring systems have been proposed to account for toxicity grades, but they are difficult to implement because of the use of complicated dose–toxicity models and the requirement to refit the model at each decision of dose escalation and de-escalation. We propose a generalized Bayesian optimal interval design, gBOIN, that accommodates various existing toxicity grade scoring systems under a unified framework. As a model-assisted design, gBOIN derives its optimal decision rule on the basis of the exponential family of distributions but is carried out in a simple way as the algorithm-based design: its decision of dose escalation and de-escalation involves only a simple comparison of the sample mean of the end point with two prespecified dose escalation and de-escalation boundaries. No model fitting is needed. We show that gBOIN has the desirable finite property of coherence and a large sample property of consistency. Numerical studies show that gBOIN yields good performance that is comparable with or superior to that of some existing, more complicated model-based designs. A Web application for implementing gBOIN is freely available from http://www.trialdesign.org.
Detection of membrane protein–protein interaction in planta based on dual‐intein‐coupled tripartite split‐GFP association
Authors: Liu Tzu‐Yin , Chou Wen‐Chun , Chen Wei‐Yuan , Chu Ching‐Yi , Dai Chen‐Yi , Wu Pei‐Yu
Published: February 2018

Despite the great interest in identifying protein–protein interactions (PPIs) in biological systems, only a few attempts have been made at large‐scale PPI screening in planta. Unlike biochemical assays, bimolecular fluorescence complementation allows visualization of transient and weak PPIs in vivo at subcellular resolution. However, when the non‐fluorescent fragments are highly expressed, spontaneous and irreversible self‐assembly of the split halves can easily generate false positives. The recently developed tripartite split‐GFP system was shown to be a reliable PPI reporter in mammalian and yeast cells. In this study, we adapted this methodology, in combination with the β‐estradiol‐inducible expression cassette, for the detection of membrane PPIs in planta. Using a transient expression assay by agroinfiltration of Nicotiana benthamiana leaves, we demonstrate the utility of the tripartite split‐GFP association in plant cells and affirm that the tripartite split‐GFP system yields no spurious background signal even with abundant fusion proteins readily accessible to the compartments of interaction. By validating a few of the Arabidopsis PPIs, including the membrane PPIs implicated in phosphate homeostasis, we proved the fidelity of this assay for detection of PPIs in various cellular compartments in planta. Moreover, the technique combining the tripartite split‐GFP association and dual‐intein‐mediated cleavage of polyprotein precursor is feasible in stably transformed Arabidopsis plants. Our results provide a proof‐of‐concept implementation of the tripartite split‐GFP system as a potential tool for membrane PPI screens in planta.
Single organelle dynamics linked to 3D structure by correlative live‐cell imaging and 3D electron microscopy
Authors: Fermie Job , Liv Nalan , ten Brink Corlinda , van Donselaar Elly G. , Müller Wally H. , Schieber Nicole L. , Schwab Yannick , Gerritsen Hans C. , Klumperman Judith
Published: February 2018

Live‐cell correlative light‐electron microscopy (live‐cell‐CLEM) integrates live movies with the corresponding electron microscopy (EM) image, but a major challenge is to relate the dynamic characteristics of single organelles to their 3‐dimensional (3D) ultrastructure. Here, we introduce focused ion beam scanning electron microscopy (FIB‐SEM) in a modular live‐cell‐CLEM pipeline for a single organelle CLEM. We transfected cells with lysosomal‐associated membrane protein 1‐green fluorescent protein (LAMP‐1‐GFP), analyzed the dynamics of individual GFP‐positive spots, and correlated these to their corresponding fine‐architecture and immediate cellular environment. By FIB‐SEM we quantitatively assessed morphological characteristics, like number of intraluminal vesicles and contact sites with endoplasmic reticulum and mitochondria. Hence, we present a novel way to integrate multiple parameters of subcellular dynamics and architecture onto a single organelle, which is relevant to address biological questions related to membrane trafficking, organelle biogenesis and positioning. Furthermore, by using CLEM to select regions of interest, our method allows for targeted FIB‐SEM, which significantly reduces time required for image acquisition and data processing.
Apheresis buffy coat collection without photoactivation has no effect on apoptosis, cell proliferation, and total viability of mononuclear cells collected using photopheresis systems
Authors: Szczepiorkowski Zbigniew M. , Burnett Christine A. , Dumont Larry J. , Abhyankar Sunil H.
Published: February 2018

BACKGROUND

Extracorporeal photopheresis (ECP) has been approved for the treatment of advanced cutaneous T‐cell lymphoma since 1988. While the precise mechanisms resulting in clinical effects are not fully understood, the photoactivation of mononuclear cells (MNCs) using ultraviolet A (UVA) light and methoxsalen is believed to be the predominant initiating process. The effects of MNC passage through the instrument without photoactivation are unknown. The objective of this study was to evaluate the effect of cell processing through the photopheresis instruments on MNCs.

STUDY DESIGN AND METHODS

Fourteen healthy male subjects underwent one simulated ECP procedure without reinfusion of buffy coats (BCs) in a two‐center, open‐label, prospective trial. Baseline peripheral blood BC, apheresis‐separated untreated BC (BC1), and photoactivated BC (BC2) were evaluated in culture for viability by dye exclusion, apoptosis by annexin V binding, and cell proliferation response to phytohemagglutinin (PHA) stimulation by bromodeoxyuridine (BrdU) incorporation.

RESULTS

Photoactivation (BC2) resulted in 88% expression of annexin V by Day 1 of culture compared with 37 and 39% for baseline and untreated BC1. Cell viability by propidium iodide exclusion was reduced to 10% in BC2 on Day 1 versus 65 and 60% for baseline and BC1. The proliferative response to PHA stimulation was 97% inhibited in the photoactivated BC2.

CONCLUSIONS

These results demonstrate that the mechanical processes used for cell separation and processing of the BC in the absence of photoactivation do not induce a significant amount of apoptosis compared to the standard ECP with methoxsalen and UVA photoactivation.
Opinions of Art Teachers on the Standards of the International Society for Technology in Education: The Case of Western Mediterranean Region, Turkey
Authors: Konak Armağan
Published: February 2018

The purpose of this study, which is based on qualitative data, is to reveal the opinions of art teachers on the teacher standards set by the International Society for Technology in Education.It has been observed that the majority of participants of a study group are not aware of these standards, use social networks but do not use mobile applications, use the Internet for information-research purposes, and follow a news from the Internet. The participants think that students should be directed to conscious Internet use and must be educated accordingly.The study group is of the opinion that technology and the teachers’ field knowledge should be included in education training to facilitate the learning of students and to stimulate their creativity. Group members also believe that classical education and original activity design should be utilized in the design and development of learning experiences and evaluation activities, and the use of technology and applications that focus on students in order to be an example on studying and learning in this information age is needed. According to the participants, art teachers should inform students about conscious use of the Internet, and teach them to integrate life-long learning with real-life situations by participating in professional development-leadership activities. One of the participants thinks that excessive use of technology during classes will make students become used to excessive comfort. Another participant is of the opinion that the use of technology in the learning environment will not be useful.As a result of the study, the following suggestions are offered.Art teachers can be informed about teacher standards.Art teachers can be given training about involving technology in teaching-learning processes, about learning experiences and the design of the evaluation activities, and life-long learning and professional development.Studies that emphasize the importance of the use of technological resources in education can be conducted.Art teachers can be informed about conscious Internet use.
Life Stories of Parents with Autistic Children
Authors: Kocabıyık Oya Onat , Fazlıoğlu Yeşim
Published: February 2018

The major aim of this study was to determine how children diagnosed with autism shapes their parents’ lives by specifying parents’ life stories. The study group consisted of 10 parents who have children with autism. Parents who have participated in the study were determined through a preliminary interview prior to the study and in-depth interviews were conducted with volunteer parents. In the study, "Life Story Interview" list was implemented to examine the content of life stories that shape parents’ lives. The data obtained from the research were analyzed using data analysis phases of interpretative phenomenology which is one of the qualitative research models. By analyzing the data obtained in the research, 10 major themes emerged. These major themes include; diagnosis, feeling, hopes and plans, concerns and questions, social reactions / stigmatization, parenting roles, coping with, sensitivity to disease, meaning of life and development. Analyses revealed that parents with autistic children undergo through a wide variety of emotions, challenges and difficulties during their daily lives and also that good coping skill is the key to normal functioning within the family which had an autistic child.
A Study on Metacognitive Thinking Skills of University Students
Authors: Coşkun Yemliha
Published: February 2018

The purpose of this study is to investigate the university students’ metacognition thinking skills. The research is a descriptive study in the screening model.The study was carried out with 407 students from the faculties of physical education and sports, education science and letters, business administration, theology, engineering, forestry and agriculture at Kahramanmaras Sutcu Imam University during the 2016-2017 academic year. They were selected by convenience sampling method. 'Personal Information Form' and ‘Metacognitive Thinking Skills Scale’, used as data collection tools. The research data were analyzed through use of SPSS 15.0. The study has concluded that university students have higher levels of metacognitive thinking ability together with their, 'thinking skill, reflective thinking skill intended for problem solving, decision making skill, alternative evaluation' sub dimensions. There has been an increase in the level of metacognitive thinking skill as well as the increase in the class level. Students studying in the faculty of theology were determined to have the highest level of highest metacognitive thinking skills. This was followed by students studying in education, physical education and sports, science-letters, forestry, agriculture and business administration respectively.
The Greek Education System and Implications for the Turkish Education System
Authors: Karabulut Nuriye
Published: February 2018

The purpose of the current study is to make a detailed introduction to the Greek education system and to compare it with the Turkish education system to come up with some implications for the latter. To this end, the literature was reviewed. A general introduction was made to Greece and its education system was examined considering its goals, structure and process dimensions. Similar and different aspects of the Greek and Turkish education system were discussed and various suggestions were developed. The Greek and Turkish education systems have many similarities such as having a centralized structure, students’ obligation to take a general exam to get a place at university, provision of the primary and secondary education by the state. On the other hand, these two systems differ from each in many respects such as conception of secular education, duration of compulsory education, financing of higher education, administrative structure of schools, prevalence of evening classes, appointment of principals and inspection of schools. As a result of the comparison of these two education systems, in short it can be said that: If teachers’ opinions are taken into consideration in the appointment of school principals, greater importance is attached to self-assessment, development-oriented inspection is put into effect and inspectors are obliged to have a master’s degree to be an inspector in Turkey, then some important contributions can be made to the development of the Turkish education system.
Exoplanet Science in the Classroom: Learning Activities for an Introductory Physics Course
Authors: Della-Rose Devin , Carlson Randall , de La Harpe Kimberly , Novotny Steven , Polsgrove Daniel
Published: February 2018

Discovery of planets outside our solar system, known as extra-solar planets or exoplanets for short, has been at the forefront of astronomical research for over 25 years. Reports of new discoveries have almost become routine; however, the excitement surrounding them has not. Amazingly, as groundbreaking as exoplanet science is, the basic physics is quite accessible to first-year physics students, as discussed in previous TPT articles. To further illustrate this point, we developed an iOS application that generates synthetic exoplanet data to provide students and teachers with interactive learning activities. Using introductory physics concepts, we demonstrate how to estimate exoplanet mass, radius, and density from the app output. These calculations form the basis for a diverse range of classroom activities. We conclude with a summary of exoplanet science resources for teachers.
Video spectroscopy with the RSpec Explorer
Authors: Lincoln James
Published: February 2018

The January 2018 issue of The Physics Teacher saw two articles that featured the RSpec Explorer as a supplementary lab apparatus. The RSpec Explorer provides live video spectrum analysis with which teachers can demonstrate how to investigate features of a diffracted light source. In this article I provide an introduction to the device as well as a variety of suggestions for using it, some of which go beyond its originally intended design.
Robust passive reconstruction of dynamic transfer function in dual-output systems
Authors: Lanza di Scalea Francesco , Sternini Simone , Liang Albert Y.
Published: February 2018

The focus of this paper is the estimation of the dynamic transfer function between two outputs of a linear system subjected to an uncontrolled and generally unknown excitation, and accounting for possible uncorrelated noise present at both outputs. Several applications of this case exist in the passive identification of dynamic systems including the health monitoring and/or non-destructive evaluation of structures subjected to natural “ambient” excitations. It is well known that noise-robust transfer function estimation of a single-input-single-output system can be achieved by a normalized cross-power spectrum operation. This paper shows that, for the subject case of a dual-output system, particular caution must be placed in the choice of the normalization factor to apply to the cross-power spectrum of the two outputs. In particular, an “inter-segment” averaging method is proposed for the normalization factor in combination with the classical “intra-segment” averaging of the cross-power spectrum in order to estimate the transfer function between the two outputs without the influence of the excitation spectrum and of the uncorrelated noise at the two receivers. Validating results are presented for synthetic signals and for experimental signals from an application to high-speed ultrasonic rail inspection exploiting the train wheels as the “ambient” excitation.
Pharmacokinetics of Second-Line Antituberculosis Drugs in Children with Multidrug-Resistant Tuberculosis in India
Authors: Hemanth Kumar Agibothu Kupparam , Kumar Alok , Kannan Thiruvengadam , Bhatia Rakesh , Agarwal Dipti , Kumar Santosh , Dayal Rajeshwar , Singh Sheo Pratap , Ramachandran Geetha
Published: February 2018

We studied the pharmacokinetics of levofloxacin (LFX), pyrazinamide (PZA), ethionamide (ETH), and cycloserine (CS) in children with multidrug-resistant tuberculosis (MDR-TB) who were being treated according to the Revised National TB Control Programme (RNTCP) guidelines in India. This observational, pharmacokinetic study was conducted in 25 children with MDR-TB at the Sarojini Naidu Medical College, Agra, India, who were being treated with a 24-month daily regimen. Serial blood samples were collected after directly observed administration of drugs. Estimations of plasma LFX, PZA, ETH, and CS were undertaken according to validated methods by high-performance liquid chromatography. Adverse events were noted at 6 months of treatment. The peak concentration (
C
max
) of LFX was significantly higher in female than male children (11.5 μg/ml versus 7.3 μg/ml;
P
= 0.017). Children below 12 years of age had significantly higher ETH exposure (area under the concentration-time curve from 0 to 8 h [AUC
0–8
]) than those above 12 years of age (17.5 μg/ml · h versus 9.4 μg/ml;
P
= 0.030). Multiple linear regression analysis showed significant influence of gender on
C
max
of ETH and age on
C
max
and AUC
0–8
of CS. This is the first and only study from India reporting on the pharmacokinetics of LFX, ETH, PZA, and CS in children with MDR-TB treated in the Government of India program. More studies on the safety and pharmacokinetics of second-line anti-TB drugs in children with MDR-TB from different settings are required.
Membrane Curvature and the Tol-Pal Complex Determine Polar Localization of the Chemoreceptor Tar in Escherichia coli
Authors: Saaki Terrens N. V. , Strahl Henrik , Hamoen Leendert W.
Published: February 2018

Chemoreceptors are localized at the cell poles of
Escherichia coli
and other rod-shaped bacteria. Over the years, different mechanisms have been put forward to explain this polar localization, including stochastic clustering, membrane curvature-driven localization, interactions with the Tol-Pal complex, and nucleoid exclusion. To evaluate these mechanisms, we monitored the cellular localization of the aspartate chemoreceptor Tar in different deletion mutants. We did not find any indication for either stochastic cluster formation or nucleoid exclusion. However, the presence of a functional Tol-Pal complex appeared to be essential to retain Tar at the cell poles. Interestingly, Tar still accumulated at midcell in
tol
and in
pal
deletion mutants. In these mutants, the protein appears to gather at the base of division septa, a region characterized by strong membrane curvature. Chemoreceptors, like Tar, form trimers of dimers that bend the cell membrane due to a rigid tripod structure. The curvature approaches the curvature of the cell membrane generated during cell division, and localization of chemoreceptor tripods at curved membrane areas is therefore energetically favorable, as it lowers membrane tension. Indeed, when we introduced mutations in Tar that abolish the rigid tripod structure, the protein was no longer able to accumulate at midcell or the cell poles. These findings favor a model where chemoreceptor localization in
E. coli
is driven by strong membrane curvature and association with the Tol-Pal complex.

IMPORTANCE
Bacteria have exquisite mechanisms to sense and adapt to the environment they live in. One such mechanism involves the chemotaxis signal transduction pathway, in which chemoreceptors specifically bind certain attracting or repelling molecules and transduce the signals to the cell. In different rod-shaped bacteria, these chemoreceptors localize specifically to cell poles. Here, we examined the polar localization of the aspartate chemoreceptor Tar in
E. coli
and found that membrane curvature at cell division sites and the Tol-Pal protein complex localize Tar at cell division sites, the future cell poles. This study shows how membrane curvature can guide localization of proteins in a cell.
Simple limbal epithelial transplantation (SLET) in failed cultivated limbal epithelial transplantation (CLET) for unilateral chronic ocular burns
Authors: Basu Sayan , Mohan Sashwanthi , Bhalekar Swapnil , Singh Vivek , Sangwan Virender
Published: February 2018

Aims

Cultivated limbal epithelial transplantation (CLET) fails in around 20%–30% of cases. This study aimed to report the clinical outcomes of autologous simple limbal epithelial transplantation (SLET) in eyes with recurrent unilateral limbal stem cell deficiency (LSCD) due to failure of CLET.

Methods

This was a prospective case series which included 30 eyes of 30 patients who underwent SLET between 2010 and 2016 after failure of one (n=24) or two (n=6) previous CLET procedures for chronic unilateral ocular burns. The primary outcome measure was success of SLET defined on the basis of relative improvement in five objective criteria: best corrected visual acuity (BCVA), and grades of symblepharon, corneal conjunctivalisation, vascularisation and opacification.

Results

At a mean follow-up of 2.3 years, 24 (80%) of the 30 eyes maintained a successful outcome. Kaplan-Meier analysis showed a 5-year survival probability of 77%±8%. At 1 year postoperatively statistically significant improvement was noted in BCVA (logarithm of the minimum angle of resolution of 3 to 1) and in the median grades of corneal conjunctivalisation (2 to 0), vascularisation (2 to 0) and opacification (2 to 1) (P≤0.0026). In 62.5% of successful cases, BCVA improved to 20/200 or better. The success rate of SLET in failed CLET was better than that of repeat CLET (53.5%, P=0.011). None of the donor eyes developed any complications.

Conclusion

SLET is an effective alternative to CLET in eyes with recurrence of LSCD after previously failed CLET procedures. Since SLET is single-staged and less expensive, it is probably preferable to repeating CLET.
Can lay health workers support the management of hypertension? Findings of a cluster randomised trial in South Africa
Authors: Goudge Jane , Chirwa Tobias , Eldridge Sandra , Gómez-Olivé Francesc Xavier F , Kabudula Chodziwadziwa , Limbani Felix , Musenge Eustasius , Thorogood Margaret
Published: February 2018

Introduction

In low/middle-income countries with substantial HIV and tuberculosis epidemics, health services often neglect other highly prevalent chronic conditions, such as hypertension, which as a result are poorly managed. This paper reports on a study to assess the effect on hypertension management of lay health workers (LHW) working in South African rural primary healthcare clinics to support the provision of integrated chronic care.

Methods

A pragmatic cluster randomised trial with a process evaluation in eight rural clinics assessed the effect of adding two LHWs supporting nurses in providing chronic disease care in each intervention clinic over 18 months. Control clinics continued with usual care. The main outcome measure was the change in the difference of percentage of clinic users who had elevated cardiovascular risk associated with high blood pressure (BP) before and after the intervention, as measured by two cross-sectional population surveys.

Results

There was no improvement in BP control among users of intervention clinics as compared with control clinics. However, the LHWs improved clinic functioning, including overall attendance, and attendance on the correct day. All clinics faced numerous challenges, including rapidly increasing number of users of chronic care, unreliable BP machines and cuffs, intermittent drug shortages and insufficient space.

Conclusion

LHWs improved the process of providing care but improved BP control required improved clinical care by nurses which was compromised by large and increasing numbers of patients, the dominance of the vertically funded HIV programme and the poor standards of equipment in clinics.

Trial registration number

ISRCTN12128227.
Does insurance enrolment increase healthcare utilisation among rural-dwelling older adults? Evidence from the National Health Insurance Scheme in Ghana
Authors: van der Wielen Nele , Channon Andrew Amos , Falkingham Jane
Published: February 2018

Introduction

This paper examines the relationship between national health insurance enrolment and the utilisation of inpatient and outpatient healthcare for older adults in rural areas in Ghana. The Ghanaian National Health Insurance Scheme (NHIS) aims to improve affordability and increase the utilisation of healthcare. However, the system has been criticised for not being responsive to the needs of older adults. The majority of older adults in Ghana live in rural areas with poor accessibility to healthcare. With an ageing population, a specific assessment of whether the scheme has benefitted older adults, and also if the benefit is equitable, is needed.

Methods

Using the Ghanaian Living Standards Survey from 2012 to 2013, this paper uses propensity score matching to estimate the effect of enrolment within the NHIS on the utilisation of inpatient and outpatient care among older people aged 50 and over.

Results

The raw results show higher utilisation of healthcare among NHIS members, which persists after matching. NHIS members were 6% and 9% more likely to use inpatient and outpatient care, respectively, than non-members. When these increases were disaggregated for outpatient care, the non-poor and females were seen to benefit more than their poor and male counterparts. For inpatient care, the benefits of enrolment were equal by poverty status and sex. However, overall, poor older adults use health services much less than the non-poor older adults even when enrolled.

Conclusion

The results indicate that NHIS coverage does increase healthcare utilisation among rural older adults but that inequalities remain. The poor are still at a great disadvantage in their use of health services overall and benefit less from enrolment for outpatient care. The receipt of healthcare is significantly influenced by a set of auxiliary barriers to access to healthcare even where insurance should remove the financial burden of ad hoc out of pocket payments.
’Well, it literally stops me from having a life when it’s really bad': a nested qualitative interview study of patient views on the use of self-management treatments for the management of recurrent sinusitis (SNIFS trial)
Authors: Leydon Geraldine M , McDermott Lisa , Thomas Tammy , Halls Amy , Holdstock-Brown Ben , Petley Stephen , Wiseman Clare , Little Paul
Published: February 2018

Objective

To explore the experience and perceptions of illness, the decision to consult a general practitioner and the use of self-management approaches for chronic or recurrent sinusitis.

Design

Qualitative semistructured interview study.

Setting

UK primary care.

Participants

32 participants who had been participating in the ‘SNIFS’ (Steam inhalation and Nasal Irrigation For recurrent Sinusitis) trial in the South of England.

Method

Thematic analysis of semistructured telephone interviews.

Results

Participants often reported dramatic impact on both activities and their quality of life. Participants were aware of both antibiotic side effects and resistance, but if they had previously been prescribed antibiotics, many patients believed that they would be necessary for the future treatment of sinusitis. Participants used self-help treatments for short and limited periods of time only. In the context of the trial, steam inhalation used for recurrent sinusitis was described as acceptable but is seen as having limited effectiveness. Nasal irrigation was viewed as acceptable and beneficial by more patients. However, some participants reported that they would not use the treatment again due to the uncomfortable side effects they experienced, which outweighed any symptom relief, which may have resulted had they continued.

Conclusions

Steam inhalation is acceptable but seen as having limited effectiveness. Nasal irrigation is generally acceptable and beneficial for symptoms, but detailed information on the correct procedure and potential benefits of persisting may increase acceptability and adherence in those patients who find it uncomfortable.

Trial registration number

ISRCTN 88204146.
Impact of variation in functions and delivery on the effectiveness of behavioural and mood management interventions for smoking cessation in people with depression: protocol for a systematic review and meta-analysis
Authors: Taylor Gemma , Aveyard Paul , Meer Regina Van der , Toze Daniel , Stuijfzand Bobby , Kessler David , Munafò Marcus
Published: February 2018

Introduction

Tobacco is the world’s leading preventable cause of disease and death. People with depression are twice as likely to smoke and are less responsive to standard tobacco treatments as compared with the general population. A Cochrane systematic review of randomised controlled trials of smoking cessation treatment for smokers with current or historical depression found that adding mood management to usual smoking treatment improved quit rates. However, the review did not examine if variation in intervention delivery or intervention functions impacted on treatment effectiveness.

With the aim of providing information to develop tailored approaches to treating smoking for people with current depression, we will add-on to the Cochrane review in three ways: (1) use the Template for Intervention Description and Replication checklist to determine if variations in mood management delivery have impact on intervention effectiveness, (2) use the Taxonomy of Behaviour Change techniques for smoking cessation to examine which behaviour change functions are most effective for smoking cessation in people with current depression and (3) examine the difference in change in depression scores between intervention and control arms.

Methods and analysis

We will include randomised controlled trials of smokers with current depression as identified by a previous Cochrane review and the in-progress update of this Cochrane review. We will use meta-regression to examine (1) if variations in delivery of mood management impact on smoking cessation intervention effectiveness, (2) determine which behaviour change functions are most effective for smoking cessation and (3) use meta-analysis of the difference in change in depression scores between treatment arms from baseline to follow-up to determine if offering smoking cessation treatment causes psychological harm.

Ethics anddissemination

Ethical approval is not required for this study. We will disseminate the findings of this work at national and international conferences, and to relevant patient panels.

PROSPERO registration number

CRD42017070741.
Pulmonary sarcoidosis with and without extrapulmonary involvement: a cross-sectional and observational study in China
Authors: Li Cheng-Wei , Tao Ru-Jia , Zou Dan-Feng , Li Man-Hui , Xu Xin , Cao Wei-Jun
Published: February 2018

Objectives

Sarcoidosis is a multisystem disease characterised by the formation of granulomas within various organs, mainly the lungs. Several studies from different countries have been undertaken to investigate sarcoidosis with extrapulmonary involvement except from China. The objective of this study is to investigate a comparative clinical analysis in patients with pulmonary sarcoidosis with and without extrapulmonary involvement from China.

Methods

Data from inpatients diagnosed with sarcoidosis at Shanghai Pulmonary Hospital (Shanghai, China) between January 2009 and December 2014 were retrospectively collected and analysed. Six hundred and thirty-six patients with biopsy-proven sarcoidosis were included in the study, including 378 isolated pulmonary sarcoidosis and 258 pulmonary sarcoidosis plus extrapulmonary involvement.

Results

Two hundred and fifty-eight (40.6%) patients with pulmonary sarcoidosis had extrapulmonary involvement. Extrapulmonary localisations were detected mostly in extrathoracic lymph nodes (n=147) and skin (n=86). Statistically significant differences were demonstrated between patients with pulmonary sarcoidosis plus extrapulmonary involvement and patients with isolated pulmonary sarcoidosis for fatigue (16.6%vs8.3%, P<0.05), serum ACE (SACE) levels (79.0±46.9 IU/L vs 69.7±38.7 IU/L, P<0.05), and high-resolution CT (HRCT) findings (53.8%vs46.2%, P<0.05).

Conclusions

Extrapulmonary involvement is common in patients with pulmonary sarcoidosis, with the most common sites being extrathoracic lymph nodes and skin. Patients with sarcoidosis with extrapulmonary involvement are more symptomatic (fatigue), have higher SACE levels and more deteriorating HRCT findings, to which clinicians should pay attention.
Characteristics and publication fate of unregistered and retrospectively registered clinical trials submitted toThe BMJover 4 years
Authors: Loder Elizabeth , Loder Stephen , Cook Sophie
Published: February 2018

Objectives

We sought to evaluate the characteristics and publication fate of improperly registered clinical trials submitted to a medical journal (The BMJ) over a 4-year period to identify common types of registration issues and their relation to publication outcomes.

Design

Research articles submitted toThe BMJand identified as unregistered or retrospectively registered by editors were included if they reported outcomes of a clinical trial. Relevant data regarding the trials were then extracted from each paper. Trials were categorised as prospectively registered, registered in an unapproved registry, unregistered or other, and explanations for registration deficiencies were grouped into six categories. We searched PubMed and Google to determine whether, where and when improperly registered studies were subsequently published and whether registration issues were disclosed.

Results

123 research papers reporting apparently unregistered or retrospectively registered clinical trials were identified. 110 studies (89.4%) were retrospectively registered, nine (7.3%) were unregistered, three (2.4%) had been registered in an unapproved registry and one study originally lacking registration details was later discovered to have been prospectively registered. 82 studies (66.6%) were funded entirely or in part by government sources, and only seven studies (5.7%) received funding from industry. Of those papers submitted toThe BMJthrough the end of 2015, 67 of the 70 papers rejected for registration problems (95.7%) were subsequently published in another journal. The registration problem was disclosed in only 2 (2.9%).

Conclusions

Improper registration remains a problem, particularly for clinical trials that are government or foundation-funded. Nonetheless, improperly registered trials are almost always published, suggesting that medical journal editors may not actively enforce registration requirements.
Identifying positively deviant elderly medical wards using routinely collected NHS Safety Thermometer data: an observational study
Authors: Baxter Ruth , Taylor Natalie , Kellar Ian , Pye Victoria , Mohammed Mohammed A , Lawton Rebecca
Published: February 2018

Objective

The positive deviance approach seeks to identify and learn from exceptional performers. Although a framework exists to apply positive deviance within healthcare organisations, there is limited guidance to support its implementation. The approach has also rarely explored exceptional performance on broad outcomes, been implemented at ward level, or applied within the UK. This study develops and critically appraises a pragmatic method for identifying positively deviant wards using a routinely collected, broad measure of patient safety.

Design

A two-phased observational study was conducted. During phase 1, cross-sectional and temporal analyses of Safety Thermometer data were conducted to identify a discrete group of positively deviant wards that consistently demonstrated exceptional levels of safety. A group of matched comparison wards with above average performances were also identified. During phase 2, multidisciplinary staff and patients on the positively deviant and comparison wards completed surveys to explore whether their perceptions of safety supported the identification of positively deviant wards.

Setting

34 elderly medical wards within a northern region of England, UK.

Participants

Multidisciplinary staff (n=161) and patients (n=188) clustered within nine positively deviant and comparison wards.

Results

Phase 1: A combination of analyses identified five positively deviant wards that performed best in the region, outperformed their organisation and performed consistently well over 12 months. Five above average matched comparator wards were also identified. Phase 2: Staff and patient perceptions of safety generally supported the identification of positively deviant wards using Safety Thermometer data, although patient perceptions of safety were less concordant with the routinely collected data.

Conclusions

This study tentatively supports a pragmatic method of using routinely collected data to identify positively deviant elderly medical wards; however, it also highlights the various challenges that are faced when conducting the first stage of the positive deviance approach.

Trial registration number

UK Clinical Research Network Portfolio (reference-18050).
Management of atrial fibrillation in patients with rheumatic mitral stenosis
Authors: Iung Bernard , Leenhardt Antoine , Extramiana Fabrice
Published: February 2018

Atrial fibrillation (AF) is frequent in patients with rheumatic mitral stenosis (MS). Pressure overload leads to marked structural and electrical remodelling of left atrium. The frequency of persistent AF increases with age and paroxysmal, asymptomatic, AF seems even more frequent. The occurrence of AF worsens the haemodynamic tolerance of MS and markedly increases the risk of thromboembolic events. AF has a negative impact on the natural history of MS and on its outcome after commissurotomy. The respective indications of rhythm and rate control should be adapted to patient characteristics, particularly the consequences of MS, and take into account the high risk of recurrence of AF. Oral anticoagulant therapy is mandatory when AF complicates MS, regardless of its severity and CHA2DS2-VASc score. Non-vitamin K antagonists oral anticoagulants are not recommended in moderate-to-severe MS due to the lack of data. Percutaneous mitral commissurotomy does not appear to prevent the occurrence of AF in MS but should be considered as the first-line therapy when AF is associated with severe symptomatic MS, followed by the discussion of cardioversion or ablation. AF ablation should be considered in patients with mitral disease requiring intervention, but the ideal timing and techniques are difficult to determine due to the lack of appropriate specific randomised trials in patients with MS.