bluuebunny/crossref_metadata_2025 huggingface dataset:
Health-related quality of life and psychosocial impacts of a diagnosis of non-specific genital infection in symptomatic heterosexual men attending UK sexual health clinics: a feasibility study
Authors: Hill-Tout Rachel , Harding-Esch Emma M , Pacho Agata , Furegato Martina , Fuller Sebastian S , Sadiq Syed Tariq
Published: June 2018

Introduction

Non-specific genital infection (NSGI; non-Chlamydia trachomatis, non-Neisseria gonorrhoeae-associated urethritis) is a common diagnosis in symptomatic heterosexual men attending UK sexual health clinics (SHCs). but little is known about the psychosocial impact of this diagnosis.

Methods

We conducted an observational study among symptomatic heterosexual men attending SHCs to evaluate the psychosocial impact of an NSGI diagnosis compared with a diagnosis ofChlamydia trachomatis(CT),Neisseria gonorrhoeaeor no abnormalities detected focusing on the feasibility of our study methodology. Participants completed a computer-assisted self-interviewing (CASI) including two validated measures of psychosocial impact: the EQ-5D-5L health-related quality of life and Rosenberg Self-Esteem Scale, before diagnostic testing and 2 weeks after receiving test results (follow-up 1 (FU-1)) and a qualitative interview. We compared scores between diagnostic groups using paired t-tests, qualitative data were analysed thematically and feasibility was assessed by process analysis.

Results

60 men completed the baseline CASI (75% response rate). 46 (76.6%) were eligible for follow-up; 11/46 (23.9%) completed the follow-up CASI, and 3/11 (27.3%) completed the qualitative interview. 81.7% of all participants left CASI feedback at baseline: 73.5% reported the questionnaire as ‘fine’ or ‘very good’. Qualitative interview participants reported the study was acceptable. Compared with baseline, among patients completing FU-1, only patients with a diagnosis of NSGI (p<0.05) or CT (p<0.05) showed increased EQ-5D-5L Index, whereas patients with a diagnosis of NSGI (p=0.05) showed decreased mean Rosenberg Self-Esteem Scale score.

Conclusions

Although most participants indicated study acceptability at baseline, and we employed measures to increase retention (CASI questionnaires, reminder messages and a focus on men’s health), we experienced high loss to follow-up. We found that heterosexual men attending SHCs with symptoms of urethritis experience both positive and negative psychosocial impacts following their clinic attendance, which warrants further investigation.
History and publication trends in the diffusion and early uptake of indirect comparison meta-analytic methods to study drugs: animated coauthorship networks over time
Authors: Ban Joann K , Tadrous Mina , Lu Amy X , Cicinelli Erin A , Cadarette Suzanne M
Published: June 2018

Objective

To characterise the early diffusion of indirect comparison meta-analytic methods to study drugs.

Design

Systematic literature synthesis.

Data sources

Cochrane Database of Systematic Reviews, EMBASE, MEDLINE, Scopus and Web of Science.

Study selection

English language papers that used indirect comparison meta-analytic methods to study the efficacy or safety of three or more interventions, where at least one was a drug.

Data extraction

The number of publications and authors was plotted by year and type: methodological contribution, review or empirical application. Author and methodological details were summarised for empirical applications, and animated coauthorship networks were created to visualise contributors by country and affiliation type (academia, industry, government or other) over time.

Results

We identified 477 papers (74 methodological contributions, 42 reviews and 361 empirical applications) by 1689 distinct authors from 1997 to 2013. Prior to 2002, only three applications were published, with contributions from the USA (n=2) and Canada (n=1). The number of applications gradually increased annually with rapid uptake between 2011 and 2013 (n=254, 71%). Early diffusion occurred primarily in Europe with the first application credited to the UK in 2003. Application spread to other European countries in 2005, and may have been supported by regulatory requirements for drug approval. By the end of 2013, contributions included 49% credited to Europe (22% UK, 27% other), 37% credited to North America (11% Canada, 26% USA) and 14% from other regions.

Conclusion

Indirect comparison meta-analytic methods are an important innovation for health research. Although Canada and the USA were the first to apply these methods, Europe led their diffusion. The increase in uptake of these methods may have been facilitated by acceptance by regulatory agencies, which are calling for more comparative drug effect data to assist in drug accessibility and reimbursement decisions.
Common mental disorders among Indigenous people living in regional, remote and metropolitan Australia: a cross-sectional study
Authors: Nasir Bushra F , Toombs Maree R , Kondalsamy-Chennakesavan Srinivas , Kisely Steve , Gill Neeraj S , Black Emma , Hayman Noel , Ranmuthugala Geetha , Beccaria Gavin , Ostini Remo , Nicholson Geoffrey C
Published: June 2018

Objective

To determine, using face-to-face diagnostic interviews, the prevalence of common mental disorders (CMD) in a cohort of adult Indigenous Australians, the cultural acceptability of the interviews, the rates of comorbid CMD and concordance with psychiatrists’ diagnoses.

Design

Cross-sectional study July 2014–November 2016. Psychologists conducted Structured Clinical Interviews for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision Axis I Disorders (SCID-I) (n=544). Psychiatrists interviewed a subsample (n=78).

Setting

Four Aboriginal Medical Services and the general community located in urban, regional and remote areas of Southern Queensland and two Aboriginal Reserves located in New South Wales.

Participants

Indigenous Australian adults.

Outcome measures

Cultural acceptability of SCID-I interviews, standardised rates of CMD, comorbid CMD and concordance with psychiatrist diagnoses.

Results

Participants reported that the SCID-I interviews were generally culturally acceptable. Standardised rates (95% CI) of current mood, anxiety, substance use and any mental disorder were 16.2% (12.2% to 20.2%), 29.2% (24.2% to 34.1%), 12.4% (8.8% to 16.1%) and 42.2% (38.8% to 47.7%), respectively—6.7-fold, 3.8-fold, 6.9-fold and 4.2-fold higher, respectively, than those of the Australian population. Differences between this Indigenous cohort and the Australian population were less marked for 12-month (2.4-fold) and lifetime prevalence (1.3-fold). Comorbid mental disorder was threefold to fourfold higher. In subgroups living on traditional lands in Indigenous reserves and in remote areas, the rate was half that of those living in mainstream communities. Moderate-to-good concordance with psychiatrist diagnoses was found.

Conclusions

The prevalence of current CMD in this Indigenous population is substantially higher than previous estimates. The lower relative rates of non-current disorders are consistent with underdiagnosis of previous events. The lower rates among Reserve and remote area residents point to the importance of Indigenous peoples’ connection to their traditional lands and culture, and a potentially important protective factor. A larger study with random sampling is required to determine the population prevalence of CMD in Indigenous Australians.
A systematic review of epigenetic biomarkers in progression from non-dysplastic Barrett’s oesophagus to oesophageal adenocarcinoma
Authors: Nieto Tom , Tomlinson Claire L , Dretzke Janine , Bayliss Susan , Price Malcolm James , Dilworth Mark , Beggs Andrew D , Tucker Olga
Published: June 2018

Objectives

The objective of this systematic review is to identify and summarise studies which examine epigenetic biomarkers in patients with Barrett’s oesophagus (BO) and their association with progression to oesophageal adenocarcinoma (OADC). BO is a precursor lesion for OADC. There is no clinical test to predict patients who are likely to progress to OADC. An epigenetic biomarker could predict patients who are at high risk of progression from BO to OADC which could facilitate earlier diagnosis and spare those unlikely to develop cancer from regular invasive surveillance endoscopy.

Setting

A systematic search was conducted of the following databases: MEDLINE, MEDLINE in Process, EMBASE, Cochrane Central, ISI Conference Proceedings Citation Index and the British Library’s ZETOC. Studies were conducted in secondary and tertiary care settings.

Participants

All studies measuring epigenetic change in patients over 18 years old who progressed from non-dysplastic BO to OADC were included. Genetic, in vitro and studies which did not measure progression in the same patient cohort were excluded. Study inclusion and risk of bias of individual eligible studies were assessed in duplicate by two reviewers using a modified Quality in Prognostic Studies tool.

Results

14 studies met the inclusion criteria. 42 epigenetic markers were identified, and 5 studies developed models aiming to predict progression to OADC.

Conclusions

The evidence from this systematic review is suggestive of a role for p16 as an epigenetic biomarker for the progression of BO to OADC.

Prospero number

CRD42016038654.
Statewide cross-sectional survey of emergency departments’ adoption and implementation of the Ohio opioid prescribing guidelines and opioid prescribing practices
Authors: Penm Jonathan , MacKinnon Neil J , Mashni Rebecca , Lyons Michael S , Hooker Edmond A , Winstanley Erin L , Carlton-Ford Steve , Connelly Chloe , Tolle Erica , Boone Jill , Koechlin Kathleen , Defiore-Hyrmer Jolene
Published: June 2018

Study objective

To evaluate the implementation of the Ohio Emergency and Acute Care Facility Opioids and Other Controlled Substances Prescribing Guidelines and their perceived impact on local policies and practice.

Methods

The study design was a cross-sectional survey of emergency department (ED) medical directors, or appropriate person identified by the hospital, perception of the impact of the Ohio ED Opioid Prescribing Guidelines on their departments practice. All hospitals with an ED in Ohio were contacted throughout October and November 2016. Distribution followed Dillman’s Tailored Design Method, augmented with telephone recruitment. Hospital chief executive officers were contacted when necessary to encourage ED participation. Descriptive statistics were used to assess the impact of opioid prescribing policies on prescribing practices.

Results

A 92% response rate was obtained (150/163 EDs). In total, 112 (75%) of the respondents stated that their ED has an opioid prescribing policy, is adopting one or is implementing prescribing guidelines without a specific policy. Of these 112 EDs, 81 (72%) based their policy on the Ohio ED Opioid Prescribing Guidelines. The majority of respondents strongly agreed/agreed that the prescribing guidelines have increased the use of the prescription drug monitoring programme (86%) and have reduced inappropriate opioid prescribing (71%).

Conclusion

This study showed that the Ohio ED Opioid Prescribing Guidelines have been widely disseminated and that the majority of EDs in Ohio are using them to develop local policies. The majority of respondents believed that the Ohio opioid prescribing guidelines reduced inappropriate opioid prescribing. However, prescribing practices still varied greatly between EDs.
Outpatient antibiotic use in Dutch infants after 10-valent pneumococcal vaccine introduction: a time-series analysis
Authors: Fortanier Alexandre C , Venekamp Roderick P , Stellato Rebecca K , Sanders Elisabeth A M , Damoiseaux Roger A M J , Hoes Arno W , Schilder Anne M
Published: June 2018

Objective

This population-based cohort study assesses the impact of switching from a 7-valent pneumococcal conjugate vaccine (PCV) to a 10-valent PCV on outpatient antibiotic use in Dutch infants, and whether geographical vaccination coverage modifies this association.

Setting and participants

We extracted 2006–2013 anonymised antibiotic purchase data of 255 154 Dutch infants aged below 2 years from Achmea Health, a health insurance fund covering 28% of the national population.

Design and main outcome measure

Changes in monthly antibiotic use from 2006–2011 (PCV7) to 2011–2013 (PCV10) were estimated using time-series analysis accounting for seasonality and autocorrelation. Interaction terms for vaccination coverage (categorised into seven groups) and period were added to the model to test whether this association was vaccination coverage-dependent.

Results

275 337 antibiotic courses were used by 119 078 infants (461 352 person-years). PCV10 introduction was associated with a modest 1.6% overall reduction in antibiotic use (purchase rate ratio: 0.98, 95% CI: 0.98 to 0.99). Our model showed a significant difference in time trend in antibiotic use after PCV10 introduction (p=0.0084) with an increase in prescriptions in the PCV7 period (slope: 0.0023/month, 95% CI: −0.0001 to 0.0047) versus a decline in the PCV10 period (slope: −0.0089/month, 95% CI: −0.0150 to −0.0029). There was no evidence that PCV vaccination coverage affected this association, but since the largest rate ratios were observed in municipalities with the lowest vaccine coverage and had very wide accompanying CIs, our study might have insufficient power to detect such an association.

Conclusions

Switching from PCV7 to PCV10 was associated with a modest decline in outpatient antibiotic use in Dutch infants.
Accuracy and utility of using administrative healthcare databases to identify people with epilepsy: a protocol for a systematic review and meta-analysis
Authors: Mbizvo Gashirai K , Bennett Kyle , Simpson Colin R , Duncan Susan E , Chin Richard F M
Published: June 2018

Introduction

In an increasingly digital age for healthcare around the world, administrative data have become rich and accessible tools for potentially identifying and monitoring population trends in diseases including epilepsy. However, it remains unclear (1) how accurate administrative data are at identifying epilepsy within a population and (2) the optimal algorithms needed for administrative data to correctly identify people with epilepsy within a population. To address this knowledge gap, we will conduct a novel systematic review of all identified studies validating administrative healthcare data in epilepsy identification. We provide here a protocol that will outline the methods and analyses planned for the systematic review.

Methods and analysis

The systematic review described in this protocol will be conducted to follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE and Embase will be searched for studies validating administrative data in epilepsy published from 1975 to current (01 June 2018). Included studies will validate the International Classification of Disease (ICD), Ninth Revision (ICD-9) onwards (ie, ICD-9 code 345 and ICD-10 codes G40–G41) as well as other non-ICD disease classification systems used, such as Read Codes in the UK. The primary outcome will be providing pooled estimates of accuracy for identifying epilepsy within the administrative databases validated using sensitivity, specificity, positive and negative predictive values, and area under the receiver operating characteristic curves. Heterogeneity will be assessed using the I2statistic and descriptive analyses used where this is present. The secondary outcome will be the optimal administrative data algorithms for correctly identifying epilepsy. These will be identified using multivariable logistic regression models. 95% confidence intervals will be quoted throughout. We will make an assessment of risk of bias, quality of evidence, and completeness of reporting for included studies.

Ethics and dissemination

Ethical approval is not required as primary data will not be collected. Results will be disseminated in peer-reviewed journals, conference presentations and in press releases.

PROSPERO registration

CRD42017081212.
Long-term sickness absence of 32 chronic conditions: a Danish register-based longitudinal study with up to 17 years of follow-up
Authors: Nexo Mette Andersen , Carlsen Kathrine , Pedersen Jacob , Hetland Merete Lund , Watt Torquil , Hansen Sofie Mandrup , Bjorner Jakob Bue
Published: June 2018

Objectives

Sickness absence has been used as a central indicator of work disability, but has mainly been examined in single diseases, with limited follow-up time. This study identified the risk of long-term sickness absence (LTSA) of 32 chronic disease groups in the first year after diagnosis and the subsequent years.

Setting

We identified chronic disease groups prevalent in the work force (26 physical and 6 mental conditions) requiring all levels of care (primary, secondary, tertiary), by national registers of diagnoses from all hospital visits and prescribed medicine in Denmark from 1994 to 2011.

Participants

A general population sample within the working age range (18–59 years) was drawn by Statistics Denmark. Participants not working before and during the follow-up period were excluded. A total of 102 746 participants were included.

Primary and secondary outcome measures

HRs of transitions from work to LTSA of each of the chronic conditions were estimated in Cox proportional hazards models for repeated events—distinguishing between risk within the first (<1 year) and subsequent years of diagnosis (≥1 year) and an HR ratio (HRR): HR ≥1 year divided by HR <1 year.

Results

Almost all the conditions were associated with significantly increased risks of LTSA over time. The risks were generally more increased in men than in women. Three main patterns of LTSA were identified across diseases: strong decreases of LTSA from the first to subsequent years (eg, stroke in men <1 year: HR=7.55, 95% CI 6.45 to 8.85; ≥1 year HR=1.43, 95% CI 1.20 to 1.74; HRR=0.23). Moderate or small decreases in LTSA (HRR between 0.46 and 0.76). No changes (HRR between 0.92 and 0.95) or increases in elevated risks of LTSA over time (HRR between 1.02 and 1.16).

Conclusions

The 32 chronic diseases were associated with three different risk patterns of LTSA over time. These patterns implicate different strategies for managing work disability over time.
Conflict of interest among Italian medical oncologists: a national survey
Authors: DeCensi Andrea , Numico Gianmauro , Ballatori Enzo , Artioli Fabrizio , Clerico Mario , Fioretto Luisa , Livellara Virginia , Ruggeri Benedetta , Tomirotti Maurizio , Verusio Claudio , Roila Fausto
Published: June 2018

Objectives

To assess Italian medical oncologists’ opinion on the implications of conflict of interest (COI) on medical education, care and research, and to evaluate their direct financial relationships.

Design

National cross-sectional survey conducted between March and April 2017 among Italian oncologists.

Setting

Online survey sponsored by the Italian College of Medical Oncology Chiefs through its website.

Participants

Italian oncologists who filled out an anonymous questionnaire including 19 items and individual and working characteristics.

Main outcome measure

The proportion of medical oncologists perceiving COI as an outstanding issue and those receiving direct payments from industry.

Results

There were 321 respondents, representing 13% of Italian tenured medical oncologists. Overall, 62% declared direct payments from the pharmaceutical industry in the last 3 years. Sixty-eight per cent felt the majority of Italian oncologists have a COI with industry, but 59% suppose this is not greater than that of other specialties. Eighty-two per cent consider that most oncology education is supported by industry. More than 75% believe that current allocation of industry budget on marketing and promotion rather than research and development is unfair, but 75% consider it appropriate to receive travel and lodging hospitality from industry. A median net profit margin of €5000 per patient enrolled in an industry trial was considered appropriate for the employee institution. Sixty per cent agree to receive a personal fee for patients enrolled in industry trials, but 79% state this should be reported in the informed consent. Over 90% believe that scientific societies should publish a financial report of industry support. Finally, 79% disagree to being a coauthor of an article written by a medical writer when no substantial scientific contribution is made.

Conclusions

Among Italian oncologists COI is perceived as an important issue influencing costs, education, care and science. A more rigorous policy on COI should be implemented.
Relationship between sociodemographic factors and selection into UK postgraduate medical training programmes: a national cohort study
Authors: Kumwenda Ben , Cleland Jennifer A , Prescott Gordon J , Walker Kim , Johnston Peter W
Published: June 2018

Introduction

Knowledge about allocation of doctors into postgraduate training programmes is essential in terms of workforce planning, transparency and equity issues. However, this is a rarely examined topic. To address this gap in the literature, the current study examines the relationships between applicants’ sociodemographic characteristics and outcomes on the UK Foundation Training selection process.

Methods

A longitudinal, cohort study of trainees who applied for the first stage of UK postgraduate medical training in 2013–2014. We used UK Medical Education Database (UKMED) to access linked data from different sources, including medical school admissions, assessments and postgraduate training. Multivariable ordinal regression analyses were used to predict the odds of applicants being allocated to their preferred foundation schools.

Results

Applicants allocated to their first-choice foundation school scored on average a quarter of an SD above the average of all applicants in the sample. After adjusting for Foundation Training application score, no statistically significant effects were observed for gender, socioeconomic status (as determined by income support) or whether applicants entered medical school as graduates or not. Ethnicity and place of medical qualification were strong predictors of allocation to preferred foundation school. Applicants who graduated from medical schools in Wales, Scotland and Northern Ireland were 1.17 times, 3.33 times and 12.64 times (respectively), the odds of applicants who graduated from a medical school in England to be allocated to a foundation school of their choice.

Conclusions

The data provide supportive evidence for the fairness of the allocation process but highlight some interesting findings relating to ‘push-pull’ factors in medical careers decision-making. These findings should be considered when designing postgraduate training policy.
Development of a research platform for children with arthrogryposis multiplex congenita: study protocol for a pilot registry
Authors: Dahan-Oliel Noémi , Bedard Tanya , Darsaklis Vasiliki Betty , Hall Judith Goslin , van Bosse Harold J P , Hamdy Reggie C
Published: June 2018

Introduction

Arthrogryposis multiplex congenita (AMC) describes a heterogeneous group of conditions with multiple congenital contractures. These conditions may be attributed to genetic or other factors inducing decreased fetal movements, including maternal and paternal factors. Discovering the underlying genetic pathways has important repercussions for prevention, gene therapy and genetic counselling. The current literature mainly consists of small-scale, single-site studies, limiting comparability and pooling of findings across individual studies. A pilot registry for children presenting with AMC is proposed to provide the framework for a large-scale AMC registry. This registry will provide the platform to support high-quality studies to inform the distribution, clinical practice and genetics contributing to this group of conditions.

Methods and analysis

The registry will be piloted on 40 families of children from birth to 21 years of age presenting with AMC. Data will be collected on the child (demographic and newborn variables), mother and father (demographic, lifestyle habits and medical history). To promote standardised data collection, a manual of operations will be developed. Descriptive statistics will be used to summarise relevant data, regression analyses will be used to explore associations to generate hypotheses regarding factors contributing to AMC. Qualitative analysis will also be used to better describe the various phenotypes.

Ethics and dissemination

Ethics approval was obtained at the participating sites. The pilot registry will provide the platform for multisite AMC registry that will generate multiple research avenues to enhance current care and establish new therapies. Following this pilot study, the participant selection criteria will be refined and datasets will be expanded to include rehabilitation and surgical interventions, and genetic sequencing. The best timing for the questionnaire administration and frequency of follow-up prior to the implementation of a multisite AMC registry will be determined.
The impact of financial incentives to improve quality indicators in patients with diabetes in Swiss primary care: a protocol for a cluster randomised controlled trial
Authors: Meier Rahel , Muheim Leander , Senn Oliver , Rosemann Thomas , Chmiel Corinne
Published: June 2018

Introduction

There is only limited and conflicting evidence on the effectiveness of Pay-for-Performance (P4P) programmes, although they might have the potential to improve guideline adherence and quality of care. We therefore aim to test a P4P intervention in Swiss primary care practices focusing on quality indicators (QI) achievement in the treatment of patients with diabetes.

Methods and analysis

This is a cluster-randomised, two-armed intervention study with the primary care practice as unit of randomisation. The control group will receive bimonthly feedback reports containing last data of blood pressure and glycated haemoglobin (HbA1c) measurements. The intervention group will additionally be informed about a financial incentive for each percentage point improved in QI achievement. Primary outcomes are differences in process (measurement of HbA1c) and clinical QI (blood pressure control) between the two groups. Furthermore, we investigate the effect on non-incentivised QIs and on sustainability of the financial incentives. Swiss primary care practices participating in the FIRE (Family Medicine ICPC Research using Electronic Medical Record) research network are eligible for participation. The FIRE database consists of anonymised structured medical routine data from Swiss primary care practices. According to power calculations, 70 of the general practitioners contributing to the database will be randomised in either of the groups.

Ethics and dissemination

According to the Local Ethics Committee of the Canton of Zurich, the project does not fall under the scope of the law on human research and therefore no ethical consent is necessary. Results will be published in a peer-reviewed journal.

Trial registration number

ISRCTN13305645; Pre-results.
Postpartum ketoprofen treatment does not alter stress biomarkers in cows and calves experiencing assisted and unassisted parturition: a randomised controlled trial
Authors: Gladden Nicola , McKeegan Dorothy , Viora Lorenzo , Ellis Kathryn Amanda
Published: June 2018

Dystocia is considered painful and stressful for both the dam and the calf, although systematic evidence of this is limited. Few studies have investigated biochemical markers of stress and pain postpartum and whether any adverse effects are ameliorated by administration of analgesia. In this study, cow–calf pairs experiencing both mild to moderate farmer assistance and no assistance at parturition were randomly assigned to either treatment or placebo group in a two‐by‐two design (animals subject to veterinary intervention were excluded). The treatments were the NSAID ketoprofen or saline, administered within three hours of parturition. Blood samples taken in the immediate postpartum period, and at 24 hours, 48 hours and 7 days after parturition, were analysed for plasma concentrations of creatine kinase and cortisol (cows and calves) and plasma L‐lactate and total protein concentration (calves). Stress biomarkers were highest in the immediate postpartum period and declined over time (P<0.05). Cow plasma cortisol was higher in animals experiencing assisted parturition in the immediate postpartum period (P=0.023); by 24 hours no difference was evident. Intervention with NSAID analgesia did not result in beneficial changes in stress biomarkers. Based on biomarkers alone, this suggests limited benefits of NSAID treatment in unassisted or mild to moderately assisted parturition.
Perturbative solutions of the f(R)-theory of gravity in a central gravitational field and some applications
Authors: Ky Nguyen Anh , Ky Pham Van , Van Nguyen Thi Hong
Published: June 2018

Exact solutions of an f(R) -theory (of gravity) in a static central (gravitational) field have been studied in the literature quite well, but, to find and study exact solutions in the case of a non-static central field are not easy at all. There are, however, approximation methods of finding a solution in a central field which is not necessarily static. It is shown in this article that an approximate solution of an f(R)-theory in a general central field, which is not necessary to be static, can be found perturbatively around a solution of the Einstein equation in the general theory of relativity. In particular, vacuum solutions are found for f(R) of general and some special forms. Further, applications to the investigation of a planetary motion and light’s propagation in a central field are presented. An effect of an f(R)-gravity is also estimated for the SgrA*–S2 system. The latter gravitational system is much stronger than the Sun–Mercury system, thus the effect could be much stronger and, thus, much more measurable.
Downregulated GTCPH I/BH4 Pathway and Decreased Function of Circulating Endothelial Progenitor Cells and Their Relationship with Endothelial Dysfunction in Overweight Postmenopausal Women
Authors: Luo Ying , Huang Zhenhua , Liao Jinli , Liu Zhihao , Li Xiaopeng , Yao Shun , He Hao , Hu Dajun , Ren Zi , Zeng Haitao , Yan Quanneng , Zhan Hong
Published: July 2018

Endothelial progenitor cells (EPCs) have endogenous endothelium-reparative potential, but obesity impairs EPCs. Overweight premenopausal women have a normal number of circulating EPCs with functional activity, but whether EPCs in overweight postmenopausal women can repair obesity-related endothelial damage requires further investigation. For this purpose, we examined the function and number of circulating EPCs, evaluated vascular endothelial function, and explored the underlying mechanism. Compared with normal weight or overweight age-matched men, postmenopausal women (overweight or normal weight) had a diminished number of circulating EPCs and impaired vascular endothelial function, as detected by flow-mediated dilatation. Moreover, GTCPH I expression and the nitric oxide level in overweight postmenopausal women and men were significantly decreased. Together, our findings demonstrate that the number or function of circulating EPCs and endothelial function, which is partially regulated by the GTCPH I/BH4 signaling pathway, is not preserved in overweight postmenopausal women. The GTCPH I/BH4 pathway in circulating EPCs may be a potential therapeutic target for endothelial injury in overweight postmenopausal women.
Discovery of an Experimental Model of Unicuspid Aortic Valve
Authors: Weiss Robert M. , Chu Yi , Brooks Robert M. , Lund Donald D. , Cheng Justine , Zimmerman Kathy A. , Kafa Melissa K. , Sistla Phanicharan , Doshi Hardik , Shao Jian Q. , El Accaoui Ramzi N. , Otto Catherine M. , Heistad Donald D.
Published: June 2018

Background

The epithelial growth factor receptor family of tyrosine kinases modulates embryonic formation of semilunar valves. We hypothesized that mice heterozygous for a dominant loss‐of‐function mutation in epithelial growth factor receptor, which are
Egfr

Vel/+

mice, would develop anomalous aortic valves, valve dysfunction, and valvular cardiomyopathy.

Methods and Results

Aortic valves from
Egfr

Vel/+

mice and control mice were examined by light microscopy at 2.5 to 4 months of age. Additional
Egfr

Vel/+

and control mice underwent echocardiography at 2.5, 4.5, 8, and 12 months of age, followed by histologic examination. In young mice, microscopy revealed anatomic anomalies in 79% of
Egfr

Vel/+

aortic valves, which resembled human unicuspid aortic valves. Anomalies were not observed in control mice. At 12 months of age, histologic architecture was grossly distorted in
Egfr

Vel/+

aortic valves. Echocardiography detected moderate or severe aortic regurgitation, or aortic stenosis was present in 38% of
Egfr

Vel/+

mice at 2.5 months of age (N=24) and in 74% by 8 months of age. Left ventricular enlargement, hypertrophy, and reversion to a fetal myocardial gene expression program occurred in
Egfr

Vel/+

mice with aortic valve dysfunction, but not in
Egfr

Vel/+

mice with near‐normal aortic valve function. Myocardial fibrosis was minimal or absent in all groups.

Conclusions

A new mouse model uniquely recapitulates salient functional, structural, and histologic features of human unicuspid aortic valve disease, which are phenotypically distinct from other forms of congenital aortic valve disease. The new model may be useful for elucidating mechanisms by which congenitally anomalous aortic valves become critically dysfunctional.
Long‐Term Mortality of Older Patients With Acute Myocardial Infarction Treated in US Clinical Practice
Authors: Kochar Ajar , Chen Anita Y. , Sharma Puza P. , Pagidipati Neha J. , Fonarow Gregg C. , Cowper Patricia A. , Roe Matthew T. , Peterson Eric D. , Wang Tracy Y.
Published: June 2018

Background

There is limited information about the long‐term survival of older patients after myocardial infarction (
MI
).

Methods and Results

CRUSADE
(Can rapid risk stratification of unstable angina patients suppress adverse outcomes with early implementation of the ACC/AHA guidelines) was a registry of
MI
patients treated at 568 US hospitals from 2001 to 2006. We linked
MI
patients aged ≥65 years in
CRUSADE
to their Medicare data to ascertain long‐term mortality (defined as 8 years post index event). Long‐term unadjusted Kaplan–Meier mortality curves were examined among patients stratified by revascularization status. A landmark analysis conditioned on surviving the first year post‐
MI
was conducted. We used multivariable Cox regression to compare mortality risks between ST‐segment–elevation myocardial infarction and non–ST‐segment–elevation myocardial infarction patients. Among 22 295
MI
patients ≥ age 65 years (median age 77 years), we observed high rates of evidence‐based medication use at discharge: aspirin 95%, β‐blockers 94%, and statins 81%. Despite this, mortality rates were high: 24% at 1 year, 51% at 5 years, and 65% at 8 years. Eight‐year mortality remained high among patients who underwent percutaneous coronary intervention (49%), coronary artery bypass graft (46%), and among patients who survived the first year post‐
MI
(59%). Median survival was 4.8 years (25th, 75th percentiles 1.1, 8.5); among patients aged 65–74 years it was 8.2 years (3.3, 8.9) while for patients aged ≥75 years it was 3.1 years (0.6, 7.6). Eight‐year mortality was lower among ST‐segment–elevation myocardial infarction than non–ST‐segment–elevation myocardial infarction patients (53% versus 67%); this difference was not significant after adjustment (hazard ratio 0.94, 95% confidence interval, 0.88–1.00).

Conclusions

Long‐term mortality remains high among patients with
MI
in routine clinical practice, even among revascularized patients and those who survived the first year.
Systematic Review of Circulating, Biomechanical, and Genetic Markers for the Prediction of Abdominal Aortic Aneurysm Growth and Rupture
Authors: Groeneveld Menno E. , Meekel Jorn P. , Rubinstein Sidney M. , Merkestein Lisanne R. , Tangelder Geert Jan , Wisselink Willem , Truijers Maarten , Yeung Kak Khee
Published: June 2018

Background

The natural course of abdominal aortic aneurysms (
AAA
) is growth and rupture if left untreated. Numerous markers have been investigated; however, none are broadly acknowledged. Our aim was to identify potential prognostic markers for
AAA
growth and rupture.

Methods and Results

Potential circulating, biomechanical, and genetic markers were studied. A comprehensive search was conducted in PubMed, Embase, and Cochrane Library in February 2017, following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Study selection, data extraction, and methodological quality assessment were conducted by 2 independent researchers. Plausibility of markers was based on the amount of publications regarding the marker (more than 3), pooled sample size (more than 100), bias risk and statistical significance of the studies. Eighty‐two studies were included, which examined circulating (n=40), biomechanical (n=27), and genetic markers (n=7) and combinations of markers (n=8). Factors with an increased expansion risk included:
AAA
diameter (9 studies; n=1938; low bias risk), chlamydophila pneumonia (4 studies; n=311; medium bias risk), S‐elastin peptides (3 studies; n=205; medium bias risk), fluorodeoxyglucose uptake (3 studies; n=104; medium bias risk), and intraluminal thrombus size (5 studies; n=758; medium bias risk). Factors with an increased rupture risk rupture included: peak wall stress (9 studies; n=579; medium bias risk) and
AAA
diameter (8 studies; n=354; medium bias risk). No meta‐analysis was conducted because of clinical and methodological heterogeneity.

Conclusions

We identified 5 potential markers with a prognostic value for
AAA
growth and 2 for rupture. While interpreting these data, one must realize that conclusions are based on small sample sizes and clinical and methodological heterogeneity. Prospective and methodological consonant studies are strongly urged to further study these potential markers.
Impact of Angiographic Residual Stenosis on Clinical Outcomes After New‐Generation Drug‐Eluting Stents Implantation: Insights From a Pooled Analysis of the RESET and NEXT Trials
Authors: Watanabe Hiroki , Morimoto Takeshi , Shiomi Hiroki , Natsuaki Masahiro , Kawai Kazuya , Kozuma Ken , Igarashi Keiichi , Kadota Kazushige , Tanabe Kengo , Morino Yoshihiro , Hibi Kiyoshi , Akasaka Takashi , Abe Mitsuru , Suwa Satoru , Muramatsu Toshiya , Kobayashi Masakazu , Dai Kazuoki , Nakao Koichi , Tarutani Yasuhiro , Fujii Kenshi , Kimura Takeshi ,   the RESET and NEXT Investigators
Published: June 2018

Background

Previous intravascular ultrasound studies suggested the association of stent underexpansion with increased risk of stent thrombosis and restenosis. However, no previous study has addressed the association of the suboptimal angiographic result with target‐lesion revascularization (
TLR
) in patients receiving new‐generation drug‐eluting stents (
DES
).

Methods and Results

RESET
(Randomized evaluation of sirolimus‐eluting versus everolimus‐eluting stent trial) and
NEXT
(NOBORI biolimus‐eluting versus XIENCE/PROMUS everolimus‐eluting stent trial) are prospective, multicenter, randomized “
DES
versus
DES
” trials; 3196 patients and 3235 patients were enrolled in the
RESET
and
NEXT
, respectively. Using the pooled individual patient‐level data, the current study population consisted of 3679 patients who received single‐lesion treatment using new‐generation
DES
such as everolimus‐eluting stent and biolimus‐eluting stent. The study population was divided into 3 groups according to the residual in‐stent % diameter stenosis (%
DS
) after stent implantation by offline quantitative coronary angiography assessed in a core angiographic laboratory (optimal group: %
DS
<10%, intermediate group: %
DS
=10% to 20%, suboptimal group: %
DS
≧20%). The cumulative 3‐year incidence of
TLR
was significantly higher in the suboptimal group than in the intermediate and optimal groups (9.8% versus 5.8% versus 5.7%, log‐rank
P
=0.004). Even after adjusting for the clinical, angiographic, and procedural characteristics, the excess
TLR
risk of the suboptimal group relative to the optimal group remained significant (hazard ratio: 1.65, 95% confidence interval, 1.14–2.41,
P
=0.009). The excess
TLR
risk of the suboptimal group relative to the optimal group was consistently seen across all the subgroups including heavy calcification.

Conclusions

The residual angiographic in‐stent %
DS
≥20% was associated with increased risk for
TLR
in patients treated with the new‐generation
DES
.
Postural Hyperventilation as a Cause of Postural Tachycardia Syndrome: Increased Systemic Vascular Resistance and Decreased Cardiac Output When Upright in All Postural Tachycardia Syndrome Variants
Authors: Stewart Julian M. , Pianosi Paul , Shaban Mohamed A. , Terilli Courtney , Svistunova Maria , Visintainer Paul , Medow Marvin S.
Published: June 2018

Background

Postural tachycardia syndrome (
POTS
) is a heterogeneous condition. We stratified patients previously evaluated for
POTS
on the basis of supine resting cardiac output (
CO
) or with the complaint of platypnea or “shortness of breath” during orthostasis. We hypothesize that postural hyperventilation is one cause of
POTS
and that hyperventilation‐associated
POTS
occurs when initial reduction in
CO
is sufficiently large. We also propose that circulatory abnormalities normalize with restoration of
CO
2
.

Methods and Results

Fifty‐eight enrollees with POTS were compared with 16 healthy volunteer controls. Low
CO
in
POTS
was defined by a resting supine
CO
<4 L/min. Patients with shortness of breath had hyperventilation with end tidal
CO
2
<30 Torr during head‐up tilt table testing. There were no differences in height or weight between control patients and patients with POTS or differences between the
POTS
groups. Beat‐to‐beat blood pressure was measured by photoplethysmography, and
CO
was measured by ModelFlow. Systemic vascular resistance was defined as mean arterial blood pressure/
CO
. End tidal
CO
2
and cerebral blood flow velocity of the middle cerebral artery were only reduced during head‐up tilt in the hyperventilation group, whereas blood pressure was increased compared with control. We corrected the reduced end tidal
CO
2
in hyperventilation by addition of exogenous
CO
2
into a rebreathing apparatus. With added
CO
2
, heart rate, blood pressure,
CO,
and systemic vascular resistance in hyperventilation became similar to control.

Conclusions

We conclude that all
POTS
is related to decreased
CO
, decreased central blood volume, and increased systemic vascular resistance and that a variant of
POTS
is consequent to postural hyperventilation.
Continuous ST‐Monitoring Function of Implantable Cardioverter Defibrillator Detects Silent Ischemia in Patients With Coronary Artery Disease
Authors: Watanabe Tetsuya , Hirooka Keiji , Furukawa Yoshio , Yabuki Masanori , Hirata Akio , Kashiwase Kazunori , Shutta Ryu , Mine Takanao , Mizuno Hiroya , Tanaka Toshikazu , Doi Takahiro , Yoshida Akihiro , Okuyama Yuji , Nanto Shinsuke
Published: June 2018

Background

Newer implantable cardioverter defibrillators can monitor intracardiac ECGs , but their ability to detect ischemia is unclear. This study investigated the usefulness of implantable cardioverter defibrillators with an ST‐monitoring function in coronary artery disease patients.

Methods and Results

We conducted a prospective study of implantable cardioverter defibrillator patients with the ST‐monitoring function. One hundred seventy‐three patients who received implantable cardioverter defibrillators for primary or secondary prevention of sudden cardiac death. All patients underwent medical examinations at least every 6 months, with standard 12‐lead ECGs and device checks that included analysis of the ST‐monitoring function. Myocardial perfusion imaging or coronary angiography was performed during the follow‐up. The mean follow‐up duration was 23.3±7.7 months. Significant ST changes occurred in 15 patients (8.7%), of whom 14 were asymptomatic. The incidence of angina pectoris was significantly higher in the ST change (+) group than that in the ST change (−) group (28.6% versus 7.2%,
P
=0.03). In the patients who underwent myocardial perfusion imaging, the sensitivity, specificity, and negative predictive value of the ST‐monitoring feature to detect ischemia were 75.0%, 72.5%, and 93.5%, respectively. The sensitivity, specificity, and negative predictive value of the ST‐monitoring feature to predict residual stenosis evaluated using coronary angiography were 76.9%, 83.5%, and 97.5%, respectively. The percentage of patients with a septal right ventricular lead was significantly lower in the ST change (+) group than in the ST change (−) group (13.5% versus 33.5%,
P
=0.01).

Conclusions

If intracardiac ECGs ST changes are detected, it is necessary to use additional modalities even in asymptomatic patients.

Clinical Trial Registration

URL:
upload.umin.ac.jp
. Unique identifier: UMIN000011824.
Combating Corruption in the Twenty-First Century: New Approaches
Authors: Heywood Paul M.
Published: July 2018

Despite the focus placed on combating corruption over the last quarter-century, practical results have been disappointing. A small number of “success” stories cannot mask the fact that corruption continues to blight the lives of millions of citizens. This essay argues that part of the reason for the broad failure of anticorruption policies is that we have not specified clearly enough what we are seeking to address, and have paid insufficient attention to changes in how and where different forms of corruption operate in practice. Rather than sticking to unrealistic aspirations to “defeat” corruption, this essay argues that we should pay more attention to the positive promotion of integrity, supported by a better understanding of the drivers of individual behavior, particularly how these are more complex than suggested by the incentives-based literature. The final section of the essay outlines some practical measures we can take, underlining the need to focus reform efforts at both supra- and subnational levels in order to help move beyond what has become a sterile conversation about corruption.
A 20-year (1996–2015) trend in deaths as a result of burns in the Transkei subregion of South Africa
Authors: Meel Banwari L
Published: June 2018

Background

Deaths as a result of burns are unrecognised, under-reported and therefore under-estimated, especially in rural areas such as the Transkei subregion of South Africa. Burning to death is painful and preventable.

Objective

The aim of this study was to investigate a 20-year trend in deaths as a result of burns in the Transkei subregion of South Africa.

Method

A record review descriptive study was undertaken of all medico-legal autopsies performed from 1996 to 2015 at Mthatha Forensic Pathology Laboratory.

Results

In total 22,952 medico-legal autopsies were conducted at Mthatha Forensic Pathology Laboratory from 1996 to 2015. Of these, 689 (3%) were burn related. This gives an average of eight deaths resulting from burns per 100,000 of the population annually in this region. The highest rate (11.6/100,000) was recorded in 2007, and the lowest (3.3/100,000) in 2004. Males outnumbered females at a ratio of 1.6:1. Young children of aged 10 years old or younger accounted for 130 of the victims, amounting to a death rate of 1.51/100,000.

Conclusion

The number of deaths as a result of burning has more than doubled in the last 20 years (1996–2015) in the Transkei subregion of South Africa. Action to prevent these deaths is urgently required.