bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for Borrelia bavariensis Infections of Ixodes uriae within Seabird Colonies of the North Atlantic Ocean
Authors: Munro Hannah J. , Ogden Nicholas H. , Lindsay L. Robbin , Robertson Gregory J. , Whitney Hugh , Lang Andrew S.
Published: August 2017

The first report of members of the spirochete genusBorreliain the seabird tick,Ixodes uriae, and seabird colonies occurred during the early 1990s. Since then,Borreliaspp. have been detected in these ticks and seabird colonies around the world. To date, the primary species detected has beenBorrelia garinii, with rare occurrences ofBorrelia burgdorferisensu strictoandBorrelia lusitaniae.During our research onBorreliaandI. uriaein seabird colonies of Newfoundland and Labrador, Canada, we have identifiedBorreliabavariensisinI. uriae. To our knowledge,B. bavariensishas previously been found only in the Eurasian tick speciesIxodes persulcatusandIxodes ricinus, and it was believed to be a rodent-specificBorreliaecotype. We foundB. bavariensiswithinI. uriaefrom three seabird colonies over three calendar years. We also reanalyzedB. gariniisequences collected fromI. uriaefrom Eurasian seabird colonies and determined that sequences from two Russian seabird colonies likely also representB. bavariensis. The CanadianB. bavariensissequences fromI. uriaeanalyzed in this study cluster with previously described sequences from Asia. Overall, this is an important discovery that illustrates and expands the range of hosts and vectors forB. bavariensis, and it raises questions regarding the possible mechanisms of pathogen dispersal from Asia to North America.

IMPORTANCETo our knowledge, this is the first documentation ofB. bavariensisoutside Eurasia. Additionally, the bacterium was found in a marine ecosystem involving the seabird tickI. uriaeand its associated seabird hosts. This indicates that the epizootiology ofB. bavariensistransmission is much different from what had been described, with this species previously believed to be a rodent-specific ecotype, and it indicates that this pathogen is established, or establishing, much more widely.
Transient MutS-Based Hypermutation System for Adaptive Evolution of Lactobacillus casei to Low pH
Authors: Overbeck Tom J. , Welker Dennis L. , Hughes Joanne E. , Steele James L. , Broadbent Jeff R.
Published: August 2017

This study explored transient inactivation of the gene encoding the DNA mismatch repair enzyme MutS as a tool for adaptive evolution of
Lactobacillus casei
. MutS deletion derivatives of
L. casei
12A and ATCC 334 were constructed and subjected to a 100-day adaptive evolution process to increase lactic acid resistance at low pH. Wild-type parental strains were also subjected to this treatment. At the end of the process, the Δ
mutS
lesion was repaired in representative
L. casei
12A and ATCC 334 Δ
mutS
mutant isolates. Growth studies in broth at pH 4.0 (titrated with lactic acid) showed that all four adapted strains grew more rapidly, to higher cell densities, and produced significantly more lactic acid than untreated wild-type cells. However, the adapted Δ
mutS
derivative mutants showed the greatest increases in growth and lactic acid production. Further characterization of the
L. casei
12A-adapted Δ
mutS
derivative revealed that it had a significantly smaller cell volume, a rougher cell surface, and significantly better survival at pH 2.5 than parental
L. casei
12A. Genome sequence analysis confirmed that transient
mutS
inactivation decreased DNA replication fidelity in both
L. casei
strains, and it identified genetic changes that might contribute to the lactic acid-resistant phenotypes of adapted cells. Targeted inactivation of three genes that had acquired nonsense mutations in the adapted
L. casei
12A Δ
mutS
mutant derivative showed that NADH dehydrogenase (
ndh
), phosphate transport ATP-binding protein PstB (
pstB
), and two-component signal transduction system (TCS) quorum-sensing histidine protein kinase (
hpk
) genes act in combination to increase lactic acid resistance in
L. casei
12A.

IMPORTANCE
Adaptive evolution has been applied to microorganisms to increase industrially desirable phenotypes, including acid resistance. We developed a method to increase the adaptability of
Lactobacillus casei
12A and ATCC 334 through transient inactivation of the DNA mismatch repair enzyme MutS. Here, we show this method was effective in increasing the resistance of
L. casei
to lactic acid at low pH. Additionally, we identified three genes that contribute to increased acid resistance in
L. casei
12A. These results provide valuable insight on methods to enhance an organism's fitness to complex phenotypes through adaptive evolution and targeted gene inactivation.
Crystal Structure and Substrate Specificity Modification of Acetyl Xylan Esterase from Aspergillus luchuensis
Authors: Komiya Dai , Hori Akane , Ishida Takuya , Igarashi Kiyohiko , Samejima Masahiro , Koseki Takuya , Fushinobu Shinya
Published: August 2017

Acetyl xylan esterase (AXE) catalyzes the hydrolysis of the acetyl bonds present in plant cell wall polysaccharides. Here, we determined the crystal structure of AXE from
Aspergillus luchuensis
(
Al
AXEA), providing the three-dimensional structure of an enzyme in the Esterase_phb family.
Al
AXEA shares its core α/β-hydrolase fold structure with esterases in other families, but it has an extended central β-sheet at both its ends and an extra loop. Structural comparison with a ferulic acid esterase (FAE) from
Aspergillus niger
indicated that
Al
AXEA has a conserved catalytic machinery: a catalytic triad (Ser119, His259, and Asp202) and an oxyanion hole (Cys40 and Ser120). Near the catalytic triad of
A
lAXEA, two aromatic residues (Tyr39 and Trp160) form small pockets at both sides. Homology models of fungal FAEs in the same Esterase_phb family have wide pockets at the corresponding sites because they have residues with smaller side chains (Pro, Ser, and Gly). Mutants with site-directed mutations at Tyr39 showed a substrate specificity similar to that of the wild-type enzyme, whereas those with mutations at Trp160 acquired an expanded substrate specificity. Interestingly, the Trp160 mutants acquired weak but significant type B-like FAE activity. Moreover, the engineered enzymes exhibited ferulic acid-releasing activity from wheat arabinoxylan.

IMPORTANCE
Hemicelluloses in the plant cell wall are often decorated by acetyl and ferulic acid groups. Therefore, complete and efficient degradation of plant polysaccharides requires the enzymes for cleaving the side chains of the polymer. Since the Esterase_phb family contains a wide array of fungal FAEs and AXEs from fungi and bacteria, our study will provide a structural basis for the molecular mechanism of these industrially relevant enzymes in biopolymer degradation. The structure of the Esterase_phb family also provides information for bacterial polyhydroxyalkanoate depolymerases that are involved in biodegradation of thermoplastic polymers.
Ornithine Decarboxylase-Mediated Production of Putrescine Influences Ganoderic Acid Biosynthesis by Regulating Reactive Oxygen Species in Ganoderma lucidum
Authors: Wu Chen-Gao , Tian Jia-Long , Liu Rui , Cao Peng-Fei , Zhang Tian-Jun , Ren Ang , Shi Liang , Zhao Ming-Wen
Published: August 2017

Putrescine is an important polyamine that participates in a variety of stress responses. Ornithine decarboxylase (ODC) is a key enzyme that catalyzes the biosynthesis of putrescine. A homolog of the gene encoding ODC was cloned from
Ganoderma lucidum
. In the
ODC
-silenced strains, the transcript levels of the
ODC
gene and the putrescine content were significantly decreased. The
ODC
-silenced strains were more sensitive to oxidative stress. The content of ganoderic acid was increased by approximately 43 to 46% in the
ODC
-silenced strains. The content of ganoderic acid could be recovered after the addition of exogenous putrescine. Additionally, the content of reactive oxygen species (ROS) was significantly increased by approximately 1.3-fold in the
ODC
-silenced strains. The ROS content was significantly reduced after the addition of exogenous putrescine. The gene transcript levels and the activities of four major antioxidant enzymes were measured to further explore the effect of putrescine on the intracellular ROS levels. Further studies showed that the effect of the ODC-mediated production of putrescine on ROS might be a factor influencing the biosynthesis of ganoderic acid. Our study reports the role of putrescine in large basidiomycetes, providing a basis for future studies of the physiological functions of putrescine in microbes.

IMPORTANCE
It is well known that ODC and the ODC-mediated production of putrescine play an important role in resisting various environmental stresses, but there are few reports regarding the mechanisms underlying the effect of putrescine on secondary metabolism in microorganisms, particularly in fungi.
G. lucidum
is gradually becoming a model organism for studying environmental regulation and metabolism. In this study, a homolog of the gene encoding ODC was cloned in
Ganoderma lucidum
. We found that the transcript level of the
ODC
gene and the content of putrescine were significantly decreased in the
ODC
-silenced strains. The content of ganoderic acid was significantly increased in the
ODC
-silenced strains. Further studies showed that the effect of the ODC-mediated production of putrescine on ROS might be a factor influencing the biosynthesis of ganoderic acid. Our study reports the role of putrescine in large basidiomycetes, providing a basis for future studies of the physiological functions of putrescine in microbes.
Transcriptional Analysis of an Ammonium-Excreting Strain of Azotobacter vinelandii Deregulated for Nitrogen Fixation
Authors: Barney Brett M. , Plunkett Mary H. , Natarajan Velmurugan , Mus Florence , Knutson Carolann M. , Peters John W.
Published: August 2017

Biological nitrogen fixation is accomplished by a diverse group of organisms known as diazotrophs and requires the function of the complex metalloenzyme nitrogenase. Nitrogenase and many of the accessory proteins required for proper cofactor biosynthesis and incorporation into the enzyme have been characterized, but a complete picture of the reaction mechanism and key cellular changes that accompany biological nitrogen fixation remain to be fully elucidated. Studies have revealed that specific disruptions of the antiactivator-encoding gene
nifL
result in the deregulation of the
nif
transcriptional activator NifA in the nitrogen-fixing bacterium
Azotobacter vinelandii
, triggering the production of extracellular ammonium levels approaching 30 mM during the stationary phase of growth. In this work, we have characterized the global patterns of gene expression of this high-ammonium-releasing phenotype. The findings reported here indicated that cultures of this high-ammonium-accumulating strain may experience metal limitation when grown using standard Burk's medium, which could be amended by increasing the molybdenum levels to further increase the ammonium yield. In addition, elevated levels of nitrogenase gene transcription are not accompanied by a corresponding dramatic increase in hydrogenase gene transcription levels or hydrogen uptake rates. Of the three potential electron donor systems for nitrogenase, only the
rnf1
gene cluster showed a transcriptional correlation to the increased yield of ammonium. Our results also highlight several additional genes that may play a role in supporting elevated ammonium production in this aerobic nitrogen-fixing model bacterium.

IMPORTANCE
The transcriptional differences found during stationary-phase ammonium accumulation show a strong contrast between the deregulated (
nifL
-disrupted) and wild-type strains and what was previously reported for the wild-type strain under exponential-phase growth conditions. These results demonstrate that further improvement of the ammonium yield in this nitrogenase-deregulated strain can be obtained by increasing the amount of available molybdenum in the medium. These results also indicate a potential preference for one of two ATP synthases present in
A. vinelandii
as well as a prominent role for the membrane-bound hydrogenase over the soluble hydrogenase in hydrogen gas recycling. These results should inform future studies aimed at elucidating the important features of this phenotype and at maximizing ammonium production by this strain.
How do different brands of size 1 laryngeal mask airway compare with face mask ventilation in a dedicated laryngeal mask airway teaching manikin?
Authors: Tracy Mark Brian , Priyadarshi Archana , Goel Dimple , Lowe Krista , Huvanandana Jacqueline , Hinder Murray
Published: August 2017

Background

International neonatal resuscitation guidelines recommend the use of laryngeal mask airway (LMA) with newborn infants (≥34 weeks’ gestation or >2 kg weight) when bag-mask ventilation (BMV) or tracheal intubation is unsuccessful. Previous publications do not allow broad LMA device comparison.

Objective

To compare delivered ventilation of seven brands of size 1 LMA devices with two brands of face mask using self-inflating bag (SIB).

Design

40 experienced neonatal staff provided inflation cycles using SIB with positive end expiratory pressure (PEEP) (5 cmH2O) to a specialised newborn/infant training manikin randomised for each LMA and face mask. All subjects received prior education in LMA insertion and BMV.

Results

12 415 recorded inflations for LMAs and face masks were analysed. Leak detected was lowest with i-gel brand, with a mean of 5.7% compared with face mask (triangular 42.7, round 35.7) and other LMAs (45.5–65.4) (p<0.001). Peak inspiratory pressure was higher with i-gel, with a mean of 28.9 cmH2O compared with face mask (triangular 22.8, round 25.8) and other LMAs (14.3–22.0) (p<0.001). PEEP was higher with i-gel, with a mean of 5.1 cmH2O compared with face mask (triangular 3.0, round 3.6) and other LMAs (0.6–2.6) (p<0.001). In contrast to other LMAs examined, i-gel had no insertion failures and all users found i-gel easy to use.

Conclusion

This study has shown dramatic performance differences in delivered ventilation, mask leak and ease of use among seven different brands of LMA tested in a manikin model. This coupled with no partial or complete insertion failures and ease of use suggests i-gel LMA may have an expanded role with newborn resuscitation as a primary resuscitation device.
Primary care physicians’ utilization of type 2 diabetes screening guidelines and referrals to behavioral interventions: a survey-linked retrospective study
Authors: Mehta Sandhya , Mocarski Michelle , Wisniewski Tami , Gillespie Karin , Narayan K M Venkat , Lang Kathleen
Published: August 2017

Objective

To assess primary care physicians’ (PCPs) knowledge of type 2 diabetes screening guidelines (American Diabetes Association (ADA) and 2008 US Preventive Services Task Force (USPSTF)), the alignment between their self-reported adherence and actual practice, and how often PCPs recommended diabetes prevention and self-management education programs (DPP/DSME).

Research design and methods

An online survey of PCPs to understand knowledge and adherence toward use of USPSTF/ADA guidelines and recommendation of DPP/DSME. Patient data from electronic medical records (EMRs) for each PCP were used to identify rates of screening in eligible patients as per guidelines and the two sources were compared to assess concordance.

Results

Of 305 surveyed physicians, 38% reported use of both guidelines (33% use ADA only, 25% USPSTF only). Approximately one-third of physicians who reported use of USPSTF/ADA guidelines had non-concordant EMR data. Similarly, while most PCPs reported they are ‘very likely’ to screen patients with risk factors listed in guidelines, for each criterion at least one-fourth (24%) of PCPs survey responses were non-concordant with EMRs. PCPs reported they provide referral to DPP and DSME on average to 45% and 67% of their newly diagnosed patients with pre-diabetes and diabetes, respectively.

Conclusion

Findings show disconnect between PCPs’ perceptions of adherence to screening guidelines and actual practice, and highlight limited referrals to DPP/DSME programs. More research is needed to understand barriers to guideline consistent screening and uptake of DPP/DSME, particularly in light of recent policy changes such as the linking USPSTF criteria to reimbursement and expected Medicare DPP reimbursement in 2018.
Association of tobacco advertising, promotion and sponsorship (TAPS) exposure and cigarette use among Nigerian adolescents: implications for current practices, products and policies
Authors: Chido-Amajuoyi Onyema G , Mantey Dale S , Clendennen Stephanie L , Pérez Adriana
Published: August 2017

Background

This study investigates the association between exposure to tobacco advertising, promotion and sponsorship (TAPS) and cigarette use behaviours among adolescents in five Nigerian regions. This is imperative given a 2015 WHO report on the global tobacco epidemic, revealing Nigeria has not met any of the MPOWER TAPS ban indicators instituted since 2008.

Methods

Secondary data analysis of the 2008 Global Youth Tobacco Survey for Nigeria. Participants were 1399 adolescents, representative of 5 Nigerian regions. Weighted multivariable logistic regression models were used to assess the relationship between TAPS exposure and (1) past 30-day (current) cigarette use, (2) ever cigarette use and (3) susceptibility to use cigarettes among never cigarette users. Sensitivity analysis via complete case analysis and multiple imputation were conducted.

Results

Ninety-five per cent of Nigerian adolescents reported exposure to TAPS. Among adolescents who had never smoked, 15% were susceptible to use cigarettes. Cumulative TAPS exposure was significantly associated with both an increased odds of current cigarette use (AOR: 1.73; 95% CI 1.09 to2.99) and ever cigarette use (AOR: 1.29; 95% CI 1.15 to1.45); as well as increased susceptibility to cigarette smoking (AOR: 1.18; 95% CI 1.03 to 1.34), among non-smokers.

Conclusion

Given study results, the emergence of new tobacco products and novel platforms for TAPS globally, implementation of existing policies and enhancement of efforts to attain comprehensive bans on all forms of direct and indirect TAPS in line with article 13 of the WHO Framework Convention on Tobacco Control are needed to reduce TAPS exposure and curtail tobacco use in Nigeria.
Causes of and contributors to infant mortality in a rural community of North India: evidence from verbal and social autopsy
Authors: Rai Sanjay Kumar , Kant Shashi , Srivastava Rahul , Gupta Priti , Misra Puneet , Pandav Chandrakant Sambhaji , Singh Arvind Kumar
Published: August 2017

Objective

To identify the medical causes of death and contribution of non-biological factors towards infant mortality by a retrospective analysis of routinely collected data using verbal and social autopsy tools.

Setting

The study site was Health and Demographic Surveillance System (HDSS), Ballabgarh, North India

Participants

All infant deaths during the years 2008–2012 were included for verbal autopsy and infant deaths from July 2012 to December 2012 were included for social autopsy.

Outcome measures

Cause of death ascertained by a validated verbal autopsy tool and level of delay based on a three-delay model using the INDEPTH social autopsy tool were the main outcome measures. The level of delay was defined as follows: level 1, delay in identification of danger signs and decision making to seek care; level 2, delay in reaching a health facility from home; level 3, delay in getting healthcare at the health facility.

Results

The infant mortality rate during the study period was 46.5/1000 live births. Neonatal deaths contributed to 54.3% of infant deaths and 39% occurred on the first day of life. Birth asphyxia (31.5%) followed by low birth weight (LBW)/prematurity (26.5%) were the most common causes of neonatal death, while infection (57.8%) was the most common cause of post-neonatal death. Care-seeking was delayed among 50% of neonatal deaths and 41.2% of post-neonatal deaths. Delay at level 1 was most common and occurred in 32.4% of neonatal deaths and 29.4% of post-neonatal deaths. Deaths due to LBW/prematurity were mostly followed by delay at level 1.

Conclusion

A high proportion of preventable infant mortality still exists in an area which is under continuous health and demographic surveillance. There is a need to enhance home-based preventive care to enable the mother to identify and respond to danger signs. Verbal autopsy and social autopsy could be routinely done to guide policy interventions aimed at reduction of infant mortality.
Can promoting awareness of fetal movements and focusing interventions reduce fetal mortality? A stepped-wedge cluster randomised trial (AFFIRM)
Authors: Heazell Alexander E P , Weir Christopher J , Stock Sarah J E , Calderwood Catherine J , Burley Sarah Cunningham , Froen J Frederik , Geary Michael , Hunter Alyson , McAuliffe Fionnuala M , Murdoch Edile , Rodriguez Aryelly , Ross-Davie Mary , Scott Janet , Whyte Sonia , Norman Jane E
Published: August 2017

Background

In 2013, the stillbirth rate in the UK was 4.2 per 1000 live births, ranking 24th out of 49 high-income countries, with an annual rate of reduction of only 1.4% per year. The majority of stillbirths occur in normally formed infants, with (retrospective) evidence of placental insufficiency the most common clinical finding. Maternal perception of reduced fetal movements (RFM) is associated with placental insufficiency and increased risk of subsequent stillbirth.

This study will test the hypothesis that the introduction of a package of care to increase women's awareness of the need for prompt reporting of RFM and standardised management to identify fetal compromise with timely delivery in confirmed cases, will reduce the rate of stillbirth. Following the introduction of a similar intervention in Norway the odds of stillbirth fell by 30%, but the efficacy of this intervention (and possible adverse effects and implications for service delivery) has not been tested in a randomised trial.

Methods

We describe a stepped-wedge cluster trial design, in which participating hospitals in the UK and Ireland will be randomised to the timing of introduction of the care package. Outcomes (including the primary outcome of stillbirth) will be derived from detailed routinely collected maternity data, allowing us to robustly test our hypothesis. The degree of implementation of the intervention will be assessed in each site. A nested qualitative study will examine the acceptability of the intervention to women and healthcare providers and identify process issues including barriers to implementation.

Ethics and dissemination

Ethical approval was obtained from the Scotland A Research Ethics Committee (Ref 13/SS/0001) and from Research and Development offices in participating maternity units. The study started in February 2014 and delivery of the intervention completed in December 2016. Results of the study will be submitted for publication in peer-reviewed journals and disseminated to local investigating sites to inform education and care of women presenting with RFM.

Trial registration number

www.clinicaltrials.govNCT01777022.

Version

Protocol Version 4.2, 3 February 2017.
Protocol for the mWellcare trial: a multicentre, cluster randomised, 12-month, controlled trial to compare the effectiveness of mWellcare, an mHealth system for an integrated management of patients with hypertension and diabetes, versus enhanced usual care in India
Authors: Jha Dilip , Gupta Priti , Ajay Vamadevan S , Jindal Devraj , Perel Pablo , Prieto-Merino David , Jacob Pramod , Nyong Jonathan , Venugopal Vidya , Singh Kavita , Goenka Shifalika , Roy Ambuj , Tandon Nikhil , Patel Vikram , Prabhakaran Dorairaj
Published: August 2017

Introduction

Rising burden of cardiovascular disease (CVD) and diabetes is a major challenge to the health system in India. Innovative approaches such as mobile phone technology (mHealth) for electronic decision support in delivering evidence-based and integrated care for hypertension, diabetes and comorbid depression have potential to transform the primary healthcare system.

Methods and analysis

mWellcare trial is a multicentre, cluster randomised controlled trial evaluating the clinical and cost-effectiveness of a mHealth system and nurse managed care for people with hypertension and diabetes in rural India. mWellcare system is an Android-based mobile application designed to generate algorithm-based clinical management prompts for treating hypertension and diabetes and also capable of storing health records, sending alerts and reminders for follow-up and adherence to medication. We recruited a total of 3702 participants from 40 Community Health Centres (CHCs), with ≥90 at each of the CHCs in the intervention and control (enhanced care) arms. The primary outcome is the difference in mean change (from baseline to 1 year) in systolic blood pressure and glycated haemoglobin (HbA1c) between the two treatment arms. The secondary outcomes are difference in mean change from baseline to 1 year in fasting plasma glucose, total cholesterol, predicted 10-year risk of CVD, depression, smoking behaviour, body mass index and alcohol use between the two treatment arms and cost-effectiveness.

Ethics and dissemination

The study has been approved by the institutional Ethics Committees at Public Health Foundation of India and the London School of Hygiene and Tropical Medicine. Findings will be disseminated widely through peer-reviewed publications, conference presentations and other mechanisms.

Trial registration

mWellcare trial is registered with Clinicaltrial.gov (Registration numberNCT02480062; Pre-results) and Clinical Trial Registry of India (Registration number CTRI/2016/02/006641). The current version of the protocol is Version 2 dated 19 October 2015 and the study sponsor is Public Health Foundation of India, Gurgaon, India (www.phfi.org).
The involvement of early stage breast cancer patients during oncology consultations in Italy: a multi-centred, randomized controlled trial of a question prompt sheet versus question listing
Authors: Bottacini Alessandro , Goss Claudia , Mazzi Maria Angela , Ghilardi Alberto , Buizza Chiara , Molino Annamaria , Fiorio Elena , Nortilli Rolando , Amoroso Vito , Vassalli Lucia , Brown Richard F
Published: August 2017

Objectives

To investigate, prior to an oncology consultation, the use of a pre-prepared list of evidence based questions, Question Prompt Sheet (QPS), compared with a Question List (QL), a patient self-generated list of questions.

Design

Multi-centred, randomised controlled trial.

Setting

Secondary-care patients attending three outpatient oncology clinics in Northern Italy.

Participants

308 women completed the study. Inclusion criteria were an age between 18 and 75 years, a recent diagnosis of early stage, non-metastatic breast cancer, adequate Italian language skills, no previous oncology visits and no evidence of cognitive impairment.

Intervention

Patients received the QPS or the QL prior to the consultation, completed it without suggestion or coaching session and delivered back before the visit.The consultations were audio-recorded and analysed for the number and content of questions. Multilevel linear models were used to compare the two groups.

Outcome measures

The primary outcome was the comparison of questions asked between QPS and QL group. Secondary outcomes included satisfaction about questions asked, satisfaction with decision, and level of anxiety.

Results

Patients in the QPS and QL group asked 13 and 16 questions respectively. The difference was not significant (b=1.7, CI –0.3 to 3.6, p=0.10). A mean of 22 questions was selected in the QPS, while a mean of 2 questions was written in the QL. Patients in the QPS group were significantly less satisfied (t=3.60, p<0.01) with questions asked but wanted less additional information (t=2.20, p<0.05). Levels of patient decisional satisfaction were equivalent between groups. Similarly, anxiety levels were equal between groups prior to the consultation and decreased in similar way after the consultation.

Conclusions

Both interventions have similar impact on patients’ participation in terms of question asking during the consultation. Future research is needed in order to explore which components of the interventions are really useful and efficacious.

Trial registration

ClinicalTrials.govNCT01510964
The SIMS trial: adjustable anchored single-incision mini-slings versus standard tension-free midurethral slings in the surgical management of female stress urinary incontinence. A study protocol for a pragmatic, multicentre, non-inferiority randomised controlled trial
Authors: Abdel-Fattah Mohamed , MacLennan Graeme , Kilonzo Mary , Assassa R Phil , McCormick Kirsty , Davidson Tracey , McDonald Alison , N’Dow James , Wardle Judith , Norrie John
Published: August 2017

Introduction

Single-incision mini-slings (SIMS) represent the third generation of midurethral slings. They have been developed with the aim of offering a true ambulatory procedure for treatment of female stress urinary incontinence (SUI) with reduced morbidity and earlier recovery while maintaining similar efficacy to standard midurethral slings (SMUS). The aim of this study is to determine the clinical and cost-effectiveness of adjustable anchored SIMS compared with tension-free SMUS in the surgical management of female SUI, with 3-year follow-up.

Methods and analysis

A pragmatic, multicentre, non-inferiority randomised controlled trial.

Primary outcome measure

The primary outcome measure is the patient-reported success rate measured by the Patient Global Impression of Improvement at 12 months. The primary economic outcome will be incremental cost per quality-adjusted life year gained at 12 months.

Secondary outcome measures

The secondary outcomes measures include adverse events, objective success rates, impact on other lower urinary tract symptoms, health-related quality of life profile and sexual function, and reoperation rates for SUI. Secondary economic outcomes include National Health Service and patient primary and secondary care resource use and costs, incremental cost-effectiveness and incremental net benefit.

Statistical analysis

The statistical analysis of the primary outcome will be by intention-to-treat and also a per-protocol analysis. Results will be displayed as estimates and 95% CIs. CIs around observed differences will then be compared with the prespecified non-inferiority margin. Secondary outcomes will be analysed similarly.

Ethics and dissemination

The North of Scotland Research Ethics Committee has approved this study (13/NS/0143). The dissemination plans include HTA monograph, presentation at international scientific meetings and publications in high-impact, open-access journals. The results will be included in the updates of the National Institute for Health and Care Excellence and the European Association of Urology guidelines; these two specific guidelines directly influence practice in the UK and worldwide specialists, respectively. In addition, plain English-language summary of the main findings/results will be presented for relevant patient organisations.

Trial registration number

ISRCTN93264234. The SIMS study is currently recruiting in 20 UK research centres. The first patient was randomised on 4 February 2014, with follow-up to be completed at the end of February 2020.
Getting the right balance? A mixed logit analysis of the relationship between UK training doctors’ characteristics and their specialties using the 2013 National Training Survey
Authors: Rodriguez Santana Idaira , Chalkley Martin
Published: August 2017

Objective

To analyse how training doctors’ demographic and socioeconomic characteristics vary according to the specialty that they are training for.

Design

Descriptive statistics and mixed logistic regression analysis of cross-sectional survey data to quantify evidence of systematic relationships between doctors’ characteristics and their specialty.

Setting

Doctors in training in the United Kingdom in 2013.

Participants

27 530 doctors in training but not in their foundation year who responded to the National Training Survey 2013.

Main outcome measures

Mixed logit regression estimates and the corresponding odds ratios (calculated separately for all doctors in training and a subsample comprising those educated in the UK), relating gender, age, ethnicity, place of studies, socioeconomic background and parental education to the probability of training for a particular specialty.

Results

Being female and being white British increase the chances of being in general practice with respect to any other specialty, while coming from a better-off socioeconomic background and having parents with tertiary education have the opposite effect. Mixed results are found for age and place of studies. For example, the difference between men and women is greatest for surgical specialties for which a man is 12.121 times more likely to be training to a surgical specialty (relative to general practice) than a woman (p-value<0.01). Doctors who attended an independent school which is proxy for doctor’s socioeconomic background are 1.789 and 1.413 times more likely to be training for surgical or medical specialties (relative to general practice) than those who attended a state school (p-value<0.01).

Conclusions

There are systematic and substantial differences between specialties in respect of training doctors’ gender, ethnicity, age and socioeconomic background. The persistent underrepresentation in some specialties of women, minority ethnic groups and of those coming from disadvantaged backgrounds will impact on the representativeness of the profession into the future. Further research is needed to understand how the processes of selection and the self-selection of applicants into specialties gives rise to these observed differences.
Protein misfolding, amyotrophic lateral sclerosis and guanabenz: protocol for a phase II RCT with futility design (ProMISe trial)
Authors: Bella Eleonora Dalla , Tramacere Irene , Antonini Giovanni , Borghero Giuseppe , Capasso Margherita , Caponnetto Claudia , Chiò Adriano , Corbo Massimo , Eleopra Roberto , Filosto Massimiliano , Giannini Fabio , Granieri Enrico , Bella Vincenzo La , Lunetta Christian , Mandrioli Jessica , Mazzini Letizia , Messina Sonia , Monsurrò Maria Rosaria , Mora Gabriele , Riva Nilo , Rizzi Romana , Siciliano Gabriele , Silani Vincenzo , Simone Isabella , Sorarù Gianni , Volanti Paolo , Lauria Giuseppe
Published: August 2017

Introduction

Recent studies suggest that endoplasmic reticulum stress may play a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) through an altered regulation of the proteostasis, the cellular pathway-balancing protein synthesis and degradation. A key mechanism is thought to be the dephosphorylation of eIF2α, a factor involved in the initiation of protein translation. Guanabenz is an alpha-2-adrenergic receptor agonist safely used in past to treat mild hypertension and is now an orphan drug. A pharmacological action recently discovered is its ability to modulate the synthesis of proteins by the activation of translational factors preventing misfolded protein accumulation and endoplasmic reticulum overload. Guanabenz proved to rescue motoneurons from misfolding protein stress both in in vitro and in vivo ALS models, making it a potential disease-modifying drug in patients. It is conceivable investigating whether its neuroprotective effects based on the inhibition of eIF2α dephosphorylation can change the progression of ALS.

Methods and analyses

Protocolised Management In Sepsis is a multicentre, randomised, double-blind, placebo-controlled phase II clinical trial with futility design. We will investigate clinical outcomes, safety, tolerability and biomarkers of neurodegeneration in patients with ALS treated with guanabenz or riluzole alone for 6 months. The primary aim is to test if guanabenz can reduce the proportion of patients progressed to a higher stage of disease at 6 months compared with their baseline stage as measured by the ALS Milano-Torino Staging (ALS-MITOS) system and to the placebo group. Secondary aims are safety, tolerability and change in at least one biomarker of neurodegeneration in the guanabenz arm compared with the placebo group. Findings will provide reliable data on the likelihood that guanabenz can slow the course of ALS in a phase III trial.

Ethics and dissemination

The study protocol was approved by the Ethics Committee of IRCCS ‘Carlo Besta Foundation’ of Milan (Eudract no. 2014-005367-32 Pre-results) based on the Helsinki declaration.
Satisfaction with rehabilitative health care services among German and non-German nationals residing in Germany: a cross-sectional study
Authors: Brzoska Patrick , Sauzet Odile , Yilmaz-Aslan Yüce , Widera Teresia , Razum Oliver
Published: August 2017

Objectives

Rehabilitation following medical conditions is largely offered as in-patient service in Germany. Foreign-national residents use rehabilitative services less often than Germans and attain less favourable treatment outcomes. These differences are independent of demographic, socioeconomic and health characteristics. Satisfaction with different aspects of rehabilitative care presumably affects the effectiveness of rehabilitative services. We compared the degree of satisfaction with different domains of the rehabilitative care process between Germans and non-German nationals residing in Germany.

Methods

We used data from a cross-sectional rehabilitation patient survey annually conducted by the German Statutory Pension Insurance Scheme. The sample comprises 274 513 individuals undergoing medical rehabilitation in 642 hospitals during the years 2007–2011. Participants rated their satisfaction with different domains of rehabilitation on multi-item scales. We dichotomised each scale to low/moderate and high satisfaction. For each domain, a multilevel adjusted logistic regression analysis was conducted to examine differences in the levels of satisfaction between German and non-German nationals. Average marginal effects (AMEs) and 99.5% CI were computed as effect estimates. AMEs represent differences in the probability for the occurrence of the outcome.

Results

Turkish nationals had a higher probability for being less satisfied with most aspects of their rehabilitation, with AMEs ranging between 0.05 (99.5% CI 0.00 to 0.09) for ‘satisfaction with psychological care’ and 0.11 (99.5% CI 0.08 to 0.14) for ‘satisfaction with treatments during rehabilitation’. Patients from former Yugoslavia and from Portugal/Spain/Italy/Greece were as satisfied as Germans with most aspects of their rehabilitation.

Conclusions

Turkish nationals are less satisfied with their rehabilitative care than other population groups. This may be attributable to the diversity of the population in terms of its expectations towards rehabilitation. Rehabilitative care institutions need to provide services that are sensitive to the needs of all clients. Diversity management can contribute to this process.
Reasons for non-adherence to cardiometabolic medications, and acceptability of an interactive voice response intervention in patients with hypertension and type 2 diabetes in primary care: a qualitative study
Authors: Kassavou Aikaterini , Sutton Stephen
Published: August 2017

Objectives

This study explored the reasons for patients’ non-adherence to cardiometabolic medications, and tested the acceptability of the interactive voice response (IVR) as a way to address these reasons, and support patients, between primary care consultations.

Design, method, participants and setting

The study included face-to-face interviews with 19 patients with hypertension and/or type 2 diabetes mellitus, selected from primary care databases, and presumed to be non-adherent. Thirteen of these patients pretested elements of the IVR intervention few months later, using a think-aloud protocol. Five practice nurses were interviewed. Data were analysed using multiperspective, and longitudinalthematic analysis.

Results

Negative beliefs about taking medications, the complexity of prescribed medication regimens, and the limited ability to cope with the underlying affective state, within challenging contexts, were mentioned as important reasons for non-adherence. Nurses reported time constraints to address each patient’s different reasons for non-adherence, and limited efficacy to support patients, between primary care consultations. Patients gave positive experiential feedback about the IVR messages as a way to support them take their medicines, and provided recommendations for intervention content and delivery mode. Specifically, they liked the voice delivering the messages and the voice recognition software. For intervention content, they preferred messages that were tailored, and included messages with ‘information about health consequences’, ‘action plans’, or simple reminders for performing the behaviour.

Conclusions

Patients with hypertension and/or type 2 diabetes, and practice nurses, suggested messages tailored to each patient’s reasons for non-adherence. Participants recommended IVR as an acceptable platform to support adherence to cardiometabolic medications between primary care consultations. Future studies could usefully test the acceptability, and feasibility, of tailored IVR interventions to support medication adherence, as an adjunct to primary care.
Systematic review of preoperative physical activity and its impact on postcardiac surgical outcomes
Authors: Kehler D Scott , Stammers Andrew N , Tangri Navdeep , Hiebert Brett , Fransoo Randy , Schultz Annette S H , Macdonald Kerry , Giacomontonio Nicholas , Hassan Ansar , Légaré Jean-Francois , Arora Rakesh C , Duhamel Todd A
Published: August 2017

Objectives

The objective of this systematic review was to study the impact of preoperative physical activity levels on adult cardiac surgical patients’ postoperative: (1) major adverse cardiac and cerebrovascular events (MACCEs), (2) adverse events within 30 days, (3) hospital length of stay (HLOS), (4) intensive care unit length of stay (ICU LOS), (5) activities of daily living (ADLs), (6) quality of life, (7) cardiac rehabilitation attendance and (8) physical activity behaviour.

Methods

A systematic search of MEDLINE, Embase, AgeLine and Cochrane library for cohort studies was conducted.

Results

Eleven studies (n=5733 patients) met the inclusion criteria. Only self-reported physical activity tools were used. Few studies used multivariate analyses to compare active versus inactive patients prior to surgery. When comparing patients who were active versus inactive preoperatively, there were mixed findings for MACCE, 30 day adverse events, HLOS and ICU LOS. Of the studies that adjusted for confounding variables, five studies found a protective, independent association between physical activity and MACCE (n=1), 30-day postoperative events (n=2), HLOS (n=1) and ICU LOS (n=1), but two studies found no protective association for 30-day postoperative events (n=1) and postoperative ADLs (n=1). No studies investigated if activity status before surgery impacted quality of life or cardiac rehabilitation attendance postoperatively. Three studies found that active patients prior to surgery were more likely to be inactive postoperatively.

Conclusion

Due to the mixed findings, the literature does not presently support that self-reported preoperative physical activity behaviour is associated with postoperative cardiac surgical outcomes. Future studies should objectively measure physical activity, clearly define outcomes and adjust for clinically relevant variables.

Registration

Trial registration numberNCT02219815. PROSPERO number CRD42015023606.
Prevalence of hepatitis C virus infection and its correlates in a rural area of southwestern China: a community-based cross-sectional study
Authors: Cheng Wanting , Yang Ya , Zhou Yibiao , Xiao Penglei , Shi Yan , Gao Jianchuan , Chen Yue , Liang Song , Yihuo Wuli , Song Xiuxia , Jiang Qingwu
Published: August 2017

Objectives

Hepatitis C virus (HCV) infection is a major public health problem in southwestern China. Our aim of the study was to assess the prevalence of HCV infection and its correlates in the Yi population of this region.

Methods

A community-based survey was conducted to investigate sociodemographic characteristics and other associated factors for HCV infection in a rural area of southwestern China. Blood samples were collected and tested for antibodies to HCV. Anti-HCV positive samples were further assessed for HCV RNA.

Results

A total of 2558 participants aged≥14 years were included in our analysis. Of them, 2.8% (95% CI 2.2% to 3.5%) were positive for HCV antibody. Multiple logistic regression analysis revealed that sex (male vs female: adjusted OR (aOR)=3.30, 95% CI 1.80 to 6.07), marital status (unmarried vs married: aOR=0.27, 95% CI 0.09 to 0.80), ever using injection drug (aOR=28.65, 95% CI 15.9 to 51.64) and ever having blood transfusion (aOR=7.64, 95% CI 1.94 to 30.16) were significantly associated with HCV infection (indicated by positive HCV antibody). Stratified analysis by HIV infection found that in HIV-negative individuals, sex (male vs female: aOR=3.84, 95% CI 1.88 to 7.85), ever using injection drug (aOR=22.15, 95% CI 8.45 to 58.04), having multiple sexual partners (aOR=2.57, 95% CI 1.26 to 5.23), and ever having blood transfusion (aOR=16.54, 95% CI 4.44 to 61.58) were significantly associated with HCV infection and in HIV-positive individuals, ever using injection drug (aOR=8.96, 95% CI 3.16 to 25.38) was associated with HCV infection.

Conclusion

The data suggested a higher risk of HCV infection in this area when compared with the rest of China and some unique associated factors. Rapid scale-up of targeted interventions are needed to prevent further transmission and consequent morbidities.