bluuebunny/crossref_metadata_2025 huggingface dataset:
Open-label dose-extending placebos for opioid use disorder: a protocol for a randomised controlled clinical trial with methadone treatment
Authors: Belcher Annabelle M , Cole Thomas O , Greenblatt Aaron D , Hoag Stephen W , Epstein David H , Wagner Michael , Billing Amy S , Massey Ebonie , Hamilton Kristen R , Kozak Zofia K , Welsh Christopher J , Weintraub Eric , Wickwire Emerson M , Wish Eric D , Kaptchuk Ted J , Colloca Luana
Published: June 2019

Introduction

More than 2 million individuals in the USA have an opioid use disorder (OUD). Methadone maintenance treatment is the gold standard of medication-based treatment for OUD, but high-dose methadone is associated with cardiotoxicity and respiratory complications, among other side effects. These adverse effects make enhancing the effectiveness of lower doses of methadone an attractive therapeutic goal. Long recognised for its capacity to enhance treatment outcomes for a wide range of neuropsychiatric disorders including pain, the placebo effect offers an as-yet untested avenue to such an enhancement. This approach is particularly compelling given that individuals with substance use disorder tend to have higher salience attribution and may thereby be more sensitive to placebo effects. Our study combines two promising clinical methodologies—conditioning/dose-extension and open-label placebo—to investigate whether placebo effects can increase the effective potency of methadone in treatment-seeking OUD patients.

Methods and analysis

A total of 120 newly enrolled treatment-seeking OUD patients will be randomly assigned to one of two different groups: either methadone plus daily placebo dose-extension (PDE; treatment group) or methadone/treatment as usual (control). Participants will meet with study team members five times over the course of 3 months of treatment with methadone (baseline, 2 weeks, and 1, 2 and 3 months postbaseline). Throughout this study time period, methadone dosages will be adjusted by an addiction clinician blind to patient assignment, per standard clinical methods. The primary outcome is methadone dose at 3 months. Secondary outcomes include self-report of drug use; 3-month urine toxicology screen results; and treatment retention. Exploratory outcomes include several environmental as well as personality factors associated with OUD and with propensity to demonstrate a placebo effect.

Ethics and dissemination

Human subjects oversight for this study is provided by the University of Maryland, Baltimore and University of Maryland, College Park Institutional Review Boards. Additionally, the study protocol is reviewed annually by an independent Data and Safety Monitoring Board. Study results will be disseminated via research conference presentations and peer-reviewed publications.

Trial registration number

NCT02941809.
Primary care use of laboratory tests in Northern Ireland’s Western Health and Social Care Trust: a cross-sectional study
Authors: Bucholc Magda , O’Kane Maurice , Mullan Ciaran , Ashe Siobhan , Maguire Liam
Published: June 2019

Objectives

To describe the laboratory test ordering patterns by general practitioners (GPs) in Northern Ireland Western Health and Social Care Trust (WHSCT) and explore demographic and socioeconomic associations with test requesting.

Design

Cross-sectional study.

Setting

WHSCT, Northern Ireland.

Participants

55 WHSCT primary care medical practices that remained open throughout the study period 1 April 2011–31 March 2016.

Outcomes

To identify the temporal patterns of laboratory test ordering behaviour for eight commonly requested clinical biochemistry tests/test groups in WHSCT. To analyse the extent of variations in laboratory test requests by GPs and to explore whether these variations can be accounted for by clinical outcomes or geographical, demographic and socioeconomic characteristics.

Results

The median number of adjusted test request rates over 5 consecutive years of the study period decreased by 45.7% for urine albumin/creatinine ratio (p<0.000001) and 19.4% for lipid profiles (p<0.000001) while a 60.6%, 36.6% and 29.5% increase was observed for HbA1c(p<0.000001), immunoglobulins (p=0.000007) and prostate-speciﬁc antigen (PSA) (p=0.0003), respectively. The between-practice variation in test ordering rates increased by 272% for immunoglobulins (p=0.008) and 500% for HbA1c(p=0.0001). No statistically significant relationship between ordering activity and either demographic (age and gender) and socioeconomic factors (deprivation) or Quality and Outcome Framework scores was observed. We found the rural–urban differences in between-practice variability in ordering rates for lipid profiles, thyroid profiles, PSA and immunoglobulins to be statistically significant at the Bonferroni-adjusted significance level p<0.01.

Conclusions

We explored potential factors of the interpractice variability in the use of laboratory tests and found that differences in requesting activity appear unrelated to either demographic and socioeconomic characteristics of GP practices or clinical outcome indicators.
Dr Foster global frailty score: an international retrospective observational study developing and validating a risk prediction model for hospitalised older persons from administrative data sets
Authors: Soong John T Y , Gammall Jurgita , Liew Danny , Peden Carol Jane , Bottle Alex , Bell Derek , Cooper Carolyn , Hopper Adrian
Published: June 2019

Objectives

This study aimed to examine the prevalence of frailty coding within the Dr Foster Global Comparators (GC) international database. We then aimed to develop and validate a risk prediction model, based on frailty syndromes, for key outcomes using the GC data set.

Design

A retrospective cohort analysis of data from patients over 75 years of age from the GC international administrative data. A risk prediction model was developed from the initial analysis based on seven frailty syndrome groups and their relationship to outcome metrics. A weighting was then created for each syndrome group and summated to create the Dr Foster Global Frailty Score. Performance of the score for predictive capacity was compared with an established prognostic comorbidity model (Elixhauser) and tested on another administrative database Hospital Episode Statistics (2011-2015), for external validation.

Setting

34 hospitals from nine countries across Europe, Australia, the UK and USA.

Results

Of 6.7 million patient records in the GC database, 1.4 million (20%) were from patients aged 75 years or more. There was marked variation in coding of frailty syndromes between countries and hospitals. Frailty syndromes were coded in 2% to 24% of patient spells. Falls and fractures was the most common syndrome coded (24%). The Dr Foster Global Frailty Score was significantly associated with in-hospital mortality, 30-day non-elective readmission and long length of hospital stay. The score had significant predictive capacity beyond that of other known predictors of poor outcome in older persons, such as comorbidity and chronological age. The score’s predictive capacity was higher in the elective group compared with non-elective, and may reflect improved performance in lower acuity states.

Conclusions

Frailty syndromes can be coded in international secondary care administrative data sets. The Dr Foster Global Frailty Score significantly predicts key outcomes. This methodology may be feasibly utilised for case-mix adjustment for older persons internationally.
Here one year, gone the next? Investigating persistence of frequent emergency department attendance: a retrospective study in Australia
Authors: Lago Luise , Westley-Wise Victoria , Mullan Judy , Lambert Kelly , Zingel Rebekah , Carrigan Thomas , Triner Wayne , Eagar Kathy
Published: June 2019

Objectives

Patients are presenting to emergency departments (EDs) with increasing complexity at rates beyond population growth and ageing. Intervention studies target patients with 12 months or less of frequent attendance. However, these interventions are not well targeted since most patients do not remain frequent attenders. This paper quantifies temporary and ongoing frequent attendance and contrasts risk factors for each group.

Design

Retrospective population-based study using 10 years of longitudinal data.

Setting

An Australian geographic region that includes metropolitan and rural EDs.

Participants

332 100 residents visited any ED during the study period.

Main outcome measure

Frequent attendance was defined as seven or more visits to any ED in the region within a 12-month period. Temporary frequent attendance was defined as meeting this threshold only once, and ongoing more than once. Risk factors for temporary and ongoing frequent attenders were identified using logistic regression models for adults and children.

Results

Of 8577 frequent attenders, 80.1% were temporary and 19.9% ongoing (12.9% repeat, 7.1% persistent). Among adults, ongoing were more likely than temporary frequent attenders to be young to middle aged (aged 25–64 years), and less likely to be from a high socioeconomic area or be admitted. Ongoing frequent attenders had higher rates of non-injury presentations, in particular substance-related (OR=2.5, 99% CI 1.1 to 5.6) and psychiatric illness (OR=2.9, 99% CI 1.8 to 4.6). In comparison, children who were ongoing were more likely than temporary frequent attenders to be aged 5–15 years, and were not more likely to be admitted (OR=2.7, 99% CI 0.7 to 10.9).

Conclusions

Future intervention studies should distinguish between temporary and ongoing frequent attenders, develop specific interventions for each group and include rigorous evaluation.
Prevalence of frailty in older adults in outpatient physiotherapy in an urban region in the western part of Germany: a cross-sectional study
Authors: Braun Tobias , Thiel Christian , Ziller Carina , Rasche Julia , Bahns Carolin , Happe Lisa , Retzmann Theresa , Grüneberg Christian
Published: June 2019

Objective

To investigate the prevalence of frailty in older people in outpatient physiotherapy services in an urban region in the western part of Germany.

Design

Cross-sectional study.

Setting

Outpatient physiotherapy clinics were recruited in the municipal area of the city of Bochum, Germany, and selected randomly.

Participants

Older adults aged 65 years and older seeking outpatient physiotherapy.

Primary and secondary outcome measures

Prevalence of frailty was assessed based on the frailty phenotype model of physical frailty and the accumulation of deficit model, expressed as a Frailty Index. Prevalence was calculated for the whole sample and according to age-related, sex-related and diagnosis-related subgroups.

Results

A total of 258 participants (74±6 years, 62% female) from 11 out of 130 (8%) different physiotherapy clinics were included. Participants’ main indication for physiotherapy was an orthopaedic or surgical condition (75%). According to the model of a physical frailty phenotype, 17.8% (95% CI 13.2 to 22.5) participants were frail and 43.4% (95% CI 37.4 to 49.5) were prefrail. The Frailty Index identified 31.0% (95% CI 25.4 to 36.7) of individuals as frail. In both models, prevalence increased with age and was higher in women than in men. Slow gait speed (34%), reduced muscle strength (34%) and exhaustion (28%) were the most prevalent indicators of physical frailty.

Conclusions

Frailty is comparatively common in older patients attending physiotherapy care in Germany, with one out of three individuals being frail and every second individual being physically frail or prefrail.

Trial registration number

DRKS00009384; Results.
Research priorities and potential methodologies to inform care in subsequent pregnancies following stillbirth: a web-based survey of healthcare professionals, researchers and advocates
Authors: Wojcieszek Aleena M , Heazell Alexander EP , Middleton Philippa , Ellwood David , Silver Robert M , Flenady Vicki
Published: June 2019

Objectives

To identify research priorities and explore potential methodologies to inform care in subsequent pregnancies following a stillbirth.

Design

Web-based survey by invitation.

Participants

Multidisciplinary panel of 79 individuals involved in stillbirth research, clinical practice and/or advocacy from the international stillbirth research community (response rate=64%).

Outcome measures

Importance of 16 candidate research topics and perceived utility and appropriateness of randomised controlled trial (RCT) methodology for the evaluation of four pertinent interventions: (1) medical therapies for placental dysfunction (eg, antiplatelet agents); (2) additional antepartum fetal surveillance (eg, ultrasound scans); (3) early planned birth from 37 weeks’ gestation and (4) different forms of psychosocial support for parents and families.

Results

Candidate research topics that were rated as ‘important and urgent’ by the greatest proportion of participants were: medical therapies for placental dysfunction (81%); additional antepartum fetal surveillance (80%); the development of a core outcomes dataset for stillbirth research (79%); targeted antenatal interventions for women who have risk factors (79%) and calculating the risk of recurrent stillbirth according to specific causes of index stillbirth (79%). Whether RCT methodologies were considered appropriate for the four selected interventions varied depending on the criterion being assessed. For example, while 72% of respondents felt that RCTs were ‘the best way’ to evaluate medical therapies for placental dysfunction, fewer respondents (63%) deemed RCTs ethical in this context, and approximately only half (52%) felt that such RCTs were feasible. There was considerably less support for RCT methodology for the evaluation of different forms of psychosocial support, which was reinforced by free-text comments.

Conclusions

Five priority research topics to inform care in pregnancies after stillbirth were identified. There was support for RCTs in this area, but the panel remained divided on the ethics and feasibility of such trials. Engagement with parents and families is a critical next step.
Unmet care needs of community-dwelling stroke survivors: a protocol for systematic review and theme analysis of quantitative and qualitative studies
Authors: Lin Beilei , Ding Chunge , Mei Yongxia , Wang Panpan , Ma Fayang , Zhang Zhen-Xiang
Published: June 2019

Introduction

Stroke is a leading cause of disability worldwide. The average hospital length of stay ranges from 3 to 28 days, and after discharge home the stroke survivors will live with physical, cognitive, even psychological disorders for the rest of their lives. It is essential to review the unmet needs of stroke survivors.

Methods and analysis

A systematic review of previous quantitative and qualitative studies reporting the unmet needs of stroke survivors in their homes will be conducted. The following six databases will be searched from inception to December 2018 for relevant articles: PubMed, EMBASE, CINAHL, PsycINFO, SCOPUS and China Biology Medicine. We will include studies limited to human and published in English or Chinese, and the patients with stroke should discharge home rather than any other professional organisations including nursing homes or community rehabilitation units and so on. Data of quantitative research will be standardised for comparison, thematic analysis will be used for qualitative data and a narrative synthesis and pooled analysis of the main outcomes will be reported.

Ethics and dissemination

This review will be submitted to an international professional journal, and the detailed search strategies and analysis flowchart will be openly included as supplements. This study does not require ethical approval as no patient’s identifiable data will be used. Our findings will give a new look at the aspect of stroke survivors’ unmet needs in their long-term recovery stage, especially the trajectories of unmet needs at different timepoints. What is more, this review will demonstrate the long-term unmet needs of stroke survivors from different countries, will compare any variations between high-income and low-income regions, and the geographical differences of needs will be mapped if necessary. We will endeavour to provide as much information as possible to healthcare professionals and public health policy makers in order to promote further medical reform.

Trial registration number

CRD42018112181.
Joint impact of dementia and frailty on healthcare utilisation and outcomes: a retrospective cohort study of long-stay home care recipients
Authors: Maxwell Colleen J , Mondor Luke , Hogan David B , Campitelli Michael A , Bronskill Susan E , Seitz Dallas P , Wodchis Walter P
Published: June 2019

Objectives

To examine the associations between dementia and 1-year health outcomes (urgent hospitalisation, long-term care (LTC) admission, mortality) among long-stay home care recipients and the extent to which these associations vary by clients’ frailty level.

Design

A retrospective cohort study using linked clinical and health administrative databases.

Setting

Home care in Ontario, Canada.

Participants

Long-stay (≥60 days) care clients (n=153 125) aged ≥50 years assessed between April 2014 and March 2015.

Main outcome measures

Dementia was ascertained with a validated administrative data algorithm and frailty with a 66-item frailty index (FI) based on a previously validated FI derived from the clinical assessment. We examined associations between dementia, FI and their interactions, with 1-year outcomes using multivariable Fine-Gray competing risk (urgent hospitalisation and LTC admission) and Cox proportional hazards (mortality) models.

Results

Clients with dementia (vs without) were older (mean±SD, 83.3±7.9 vs 78.9±11.3 years, p<0.001) and more likely to be frail (30.3% vs 24.2%, p<0.001). In models adjusted for FI (as a continuous variable) and other confounders, clients with dementia showed a lower incidence of urgent hospitalisation (adjusted subdistribution HR (sHR)=0.84, 95% CI: 0.83 to 0.86) and mortality rate (adjusted HR=0.87, 95% CI: 0.84 to 0.89) but higher incidence of LTC admission (adjusted sHR=2.60, 95% CI: 2.53 to 2.67). The impact of dementia on LTC admission and mortality was significantly modified by clients’ FI (p<0.001 interaction terms), showing a lower magnitude of association (ie, attenuated positive (for LTC admission) and negative (for mortality) association) with increasing frailty.

Conclusions

The strength of associations between dementia and LTC admission and death (but not urgent hospitalisation) among home care recipients was significantly modified by their frailty status. Understanding the public health impact of dementia requires consideration of frailty levels among older populations, including those with and without dementia and varying degrees of multimorbidity.
Effects of combination drugs on antihypertensive medication adherence in a real-world setting: a Korean Nationwide Study
Authors: Kim Seung Jae , Kwon Oh Deog , Cho BeLong , Oh Seung-Won , Lee Cheol Min , Choi Ho-Chun
Published: June 2019

Objectives

We tried to clarify, by using representative national data in a real-world setting, whether single-pill combinations (SPCs) of antihypertensives actually improve medication adherence.

Design

A nationwide population-based study.

Setting

We used a 2.2% cohort (n=1 048 061) of the total population (n=46 605 433) that was randomly extracted by National Health Insurance of Korea from 2008 to 2013.

Participants

We included patients (n=116 677) who were prescribed with the same antihypertensive drugs for at least 1 year and divided them into groups of angiotensin II receptor blocker (ARB)-only, calcium channel blocker (CCB)-only, multiple-pill combinations (MPCs) and SPCs of ARB/CCB.

Primary outcome measures

Medication possession ratio (MPR), a frequently used indirect measurement method of medication adherence.

Results

Adjusted MPR was higher in combination therapy (89.7% in SPC, 87.2% in MPC) than monotherapy (81.6% in ARB, 79.7% in CCB), and MPR of SPC (89.7%, 95% CI 89.3 to 90.0) was higher than MPR of MPC (87.2%, 95% CI 86.7 to 87.7) (p<0.05). In subgroup analysis, adherence of SPC and MPC was 92.3% (95% CI 91.5 to 93.0) vs 88.1% (95% CI 87.1 to 89.0) in those aged 65–74 years and 89.3% (95% CI 88.0 to 90.7) vs 84.8% (95% CI 83.3 to 92.0) in those ≥75 years (p<0.05). According to total pill numbers, adherence of SPC and MPC was 90.9% (CI 89.8 to 92.0) vs 85.3% (95% CI 84.1 to 86.5) in seven to eight pills and 91.2% (95% CI 89.3 to 93.1) vs 82.5% (95% CI 80.6 to 84.4) in nine or more (p<0.05). The adherence difference between SPC and MPC started to increase at five to six pills and at age 50–64 years (p<0.05). When analysed according to elderly status, the adherence difference started to increase at three to four pills in the elderly (≥65 years) and at five to six in the non-elderly group (20–64 years) (p<0.05). These differences all widened further with increasing age and the total medications.

Conclusion

SPC regimens demonstrated higher adherence than MPC, and this tendency is more pronounced with increasing age and the total number of medications.
Community determinants of COPD exacerbations in elderly patients in Poland: protocol for a retrospective Big Data observational cohort study
Authors: Zakowska Izabela , Kosiek Katarzyna , Kowalczyk Anna , Grabowski Jacek , Godycki-Cwirko Maciek
Published: June 2019

Introduction

Analyses of large sets of electronic health-related data (Big Data), including local community indicators, may improve knowledge of the outcomes of chronic diseases among patients and healthcare systems. Our study will estimate the prevalence of chronic obstructive pulmonary disease (COPD) and its exacerbations in elderly patients in the Lodz region, Poland; it will also evaluate local community factors potentially associated with disease exacerbations and rank local communities according to health and local community indicators.

Methodsand analysis

Local community factors, including medical/health, socioeconomic and environmental values potentially associated with COPD exacerbations will be identified. A retrospective analysis of a cohort of about half a million people 65 years old and older, living in local communities of the Lodz region in 2016 will be performed. Relevant data will be extracted from databases, including those of the National Health Fund, Tax Office and National Statistics Centre. This cross-sectional study will include data for a 1 year period, from 1 January until 31 December 2016. The data will first be checked for quality, cleaned and analysed using data mining techniques, and then multilevel logistic regression will be used to discover the community determinants of COPD exacerbations.

Ethics and dissemination

The study protocol has been approved by the Bioethical Committee of Medical University of Lodz (RNN/248/18/KE, 10 July 2018). Our findings will be published in peer-reviewed journals and reports.
Improving transition outcomes in adolescents with permanent hearing loss
Authors: Spyridakou Chrysa , Mendis Surangi , DeVal Daniel
Published: June 2019

Young people with permanent hearing loss need to transition into adult services and engagement with the transition process is required to achieve this. Although there are clear national recommendations about the transition process and transfer to the adult services limited evidence has been published about the implementation and efficacy of transition programmes in young adults with permanent hearing loss. The primary aim of this quality improvement project was to significantly increase the number of teenagers with a clear transition protocol documented in their notes. The secondary aims were to ensure good medical and audiological outcomes based on all completing their medical investigations prior to transfer to the adult services and also based on a survey regarding attitudes to hearing aids use. A multiphase intervention programme was developed ; (1) staff update with national transition protocols, (2) development of a clear transition protocol, (3) allocated key worker (4) access and (5) engagement. Through these interventions we increased the number of teenagers who had a clear transition protocol documented in their notes from 11% to 91%. 84% of our teenagers had completed their medical investigations, although documented discussion about the investigations had been done with 100% of the cohort. 9.2 % of adolescents felt pressurised to use hearing aids compared to 35% prior to the interventions. This project resulted in clear, measurable conclusions and we have shown that we better understand the needs of our

patients and the improvement is sustainable.
Use of quick response (QR) codes to achieve timely feedback in clinical simulation settings
Authors: Onimowo Jemina Oremeyi , Knowles Gary , Wrighton Gemma , Shah Manisha
Published: June 2019

For clinical simulation to be of maximum benefit, obtaining timely feedback from participants is vital in ensuring suitable improvements are made in the content and delivery of teaching in this setting. This report reviews the literature and describes the use of quick response (QR) codes instead of paper feedback forms following simulation-based learning sessions for fourth-year medical students. This newly implemented electronic method of collecting feedback has resulted in an increase in feedback response rate, reduction in administrative workload and a reduced carbon footprint. We also discuss other QR code-based innovations currently being implemented in this setting.
Botulinum neurotoxin treatment in jerky and tremulous functional movement disorders: a double-blind, randomised placebo-controlled trial with an open-label extension
Authors: Dreissen Yasmine Emma Maria , Dijk Joke M , Gelauff Jeannette M , Zoons Evelien , van Poppelen Daniël , Contarino Maria Fiorella , Zutt Rodi , Post Bart , Munts Alexander G , Speelman Johannes D , Cath Danielle C , de Haan Rob J , Koelman Johannes HTM , Tijssen Marina A J
Published: June 2019

Objective

To study the effect of botulinum neurotoxin (BoNT) treatment in jerky and tremulous functional movement disorders (FMD).

Methods

Patients with invalidating, chronic (>1 year) symptoms were randomly assigned to two subsequent treatments with BoNT or placebo every 3 months with stratification according to symptom localisation. Improvement on the dichotomised Clinical Global Impression-Improvement scale (CGI-I) (improvement vs no change or worsening) at 4 months, assessed by investigators blinded to the allocated treatment was the primary outcome. Subsequently all patients were treated with BoNT in a ten month open-label phase.

Results

Between January 2011 and February 2015 a total of 239 patients were screened for eligibility of whom 48 patients were included. No difference was found on the primary outcome (BoNT 16 of 25 (64.0%) vs Placebo 13 of 23 patients (56.5%); proportional difference 0.075 (95% CI −0.189 to 0.327; p=0.77). Secondary outcomes (symptom severity, disease burden, disability, quality of life and psychiatric symptoms) showed no between-group differences. The open-label phase showed improvement on the CGI-I in 19/43 (44.2%) of remaining patients, with a total of 35/43 (81.4%) improvement compared with baseline.

Conclusions

In this double-blind randomised controlled trial of BoNT for chronic jerky and tremulous FMD, we found no evidence of improved outcomes compared with placebo. Motor symptoms improved in a large proportion in both groups which was sustained in the open-label phase. This study underlines the substantial potential of chronic jerky and tremulous FMD patients to recover and may stimulate further exploration of placebo-therapies in these patients.

Trial registration number

NTR2478
Evolution of prodromal parkinsonian features in a cohort ofGBAmutation-positive individuals: a 6-year longitudinal study
Authors: Avenali Micol , Toffoli Marco , Mullin Stephen , McNeil Alisdair , Hughes Derralynn A , Mehta A , Blandini Fabio , Schapira Anthony H V
Published: June 2019

Objectives

GBA1mutations are a frequent risk factor for Parkinson disease (PD). The aim of this study is to evaluate clinical features in a group ofGBA1mutation–positive individuals over a 6-year follow-up.

Methods

This is a longitudinal study on a cohort ofGBA1-positive carriers. We enrolled 31 patients with Gaucher disease type 1 (GD), 29GBA1heterozygous carriers (HetGBAgroup) and 30 controls (HC) at baseline and followed them for 6 years. We assessed baseline motor and non-motor signs of PD in all subjects using clinical questionnaires and scales (reduced Unified Multiple System Atrophy Rating Scale (UMSARS), Montreal Cognitive assessment (MoCA), University of Pennsylvania Smell Identification Test (UPSIT), REM Sleep Behavior Disorder screening questionnaire (RBDsq), Movement Disorders Society Unified Parkinson’s Disease Rating Scale motor subscale (MDS-UPDRS III) and Beck Depression Inventory (BDI). We repeated these at the 6-year follow-up alongside venous blood sampling for measurement of glucocerebrosidase enzymatic activity (GCase). We explored whether the GCase activity level was altered in leucocytes of these subjects and how it was related to development of PD.

Results

We observed a significant worsening in UMSARS, RBDsq, MDS-UPDRS III and BDI scores at the 6-year follow-up compared with baseline in both the GD and HetGBAgroups. Intergroup comparisons showed that GD subjects had significantly worse scores in UPSIT, UMSARS, MoCA and MDS-UPDRS III than HC, while HetGBAdisplayed worse outcomes in UPSIT and MDS-UPDRS III compared with HC. InGBA1mutation–positive individuals (HetGBAand GD), an UPSIT score of 23 at baseline was correlated with worse outcome at 6 years in UPSIT, MoCA, MDS-UPDRS III and BDI.

Conclusion

In this 6-year-long longitudinal study,GBA1mutation–positive subjects showed a worsening in motor and non-motor prodromal PD features.
Catering of coalition soldiers during the deployment on a military operation and the impact on their life satisfaction
Authors: Vašek Tomáš , Zdara J , Suchanek Z
Published: June 2019

Food and catering and its impact on health and life satisfaction of coalition soldiers during their deployment on a military operation in the Middle East area was the aim of our research. Our fundamental research question was how food and catering in the military operational environment affects the life satisfaction and health of deployed soldiers.
Shenzhen stroke emergency map improves access to rt-PA for patients with acute ischaemic stroke
Authors: Ye Shisheng , Hu Shiyu , Lei Zhihao , Li Zhichao , Li Weiping , Sui Yi , Ren Lijie
Published: June 2019

Prehospital delay is one of the major causes of low rate of intravenous recombinant tissue plasminogen activator (rt-PA) thrombolysis for acute ischaemic stroke in China. Regional emergency systems have been proven a successful approach to improve access to thrombolysis. Shenzhen is a high population density city with great geographical disparity of healthcare resources, leading to limited access to rt-PA thrombolysis for most patients with acute ischaemic stroke. To improve rapid access to rt-PA thrombolysis in Shenzhen, a Shenzhen stroke emergency map was implemented by Shenzhen healthcare administrations. This map comprised certification of qualified local hospitals, identification of patients with stroke, acute stroke transport protocol and maintenance of the map. We conducted a retrospective observational study to compare consecutive patients with acute stroke arriving at qualified local hospitals before and after implementation of the Shenzhen stroke emergency map. After implementation of the map, the rate of patients receiving rt-PA thrombolysis increased from 8.3% to 9.7% (p=0.003), and the rate of patients treated with endovascular thrombectomy increased from 0.9% to 1.6% (p<0.001). Sixteen of 20 hospitals have an increase in the number of patients with stroke treated with rt-PA thrombolysis. The median time between receipt of the call and arrival on the scene reduced significantly (17.0 min vs 9.0 min, p<0.001). In Shenzhen Second People’s Hospital, the median onset-to-needle time and door-to-needle time were reduced (175.5 min vs 149.5 min, p=0.039; 71.5 min vs 51.5 min, p<0.001). No statistically significant differences were found in the proportion of rt-PA-treated patients within various geographical distances. Currently, there are more than 40 cities in China implementing a stroke emergency map. The Shenzhen stroke emergency map improves access to rt-PA thrombolysis for acute ischaemic stroke, and the novel model has been expanded to multiple areas in China. Future efforts should be conducted to optimise the stroke emergency map.
Nonlinear Free Vibration Analysis of a Toroidal Pressure Vessel under Constrained Volume Condition
Authors: Jiammeepreecha Weeraphan , Chucheepsakul Somchai
Published: June 2019

This paper focussed on the large displacement nonlinear free vibration of a toroidal pressure vessel in free space under constrained volume condition. Three states of the toroidal pressure vessel surface comprising the initial unstrained surface, reference surface, and vibrating surface were considered in the energy functional of the toroidal pressure vessel system based on the principle of virtual work. For the reference surface, it was assumed that the toroidal pressure vessel has a circular cross-section and is subjected to uniform internal pressure. Nonlinear numerical solutions were obtained utilizing the FEM and a modified direct iteration technique, and compared with those generated by ABAQUS. More importantly, this study showed that the fundamental nonlinear natural frequency of a toroidal pressure vessel under the constrained volume condition was lower than that of the published results for an inflated toroidal membrane and shell.
Trabecular cutting: a novel surgical therapy to increase diastolic compliance
Authors: Oglesby Meagan , Escobedo Danny , Escobar Gladys Patricia , Fatemifar Fatemeh , Sako Edward Y. , Bailey Steven R. , Han Hai-Chao , Feldman Marc D.
Published: June 2019

Heart failure with preserved ejection fraction (HFpEF) is a common cause of hospital admission in patients over 65 yr old and has high mortality. HFpEF is characterized by left ventricular (LV) hypertrophy that reduces compliance. Current HFpEF therapies control symptoms, but no existing medications or therapies can sustainably increase LV compliance. LV trabeculae develop hypertrophy and fibrosis that contribute to reduced LV compliance. This study expands our previous results in ex vivo human hearts to show that severing LV trabeculae increases diastolic compliance in an ex vivo working rabbit heart model. Trabecular cutting was performed in ex vivo rabbit hearts set up in a working heart perfusion system perfused with oxygenated Krebs-Henseleit buffer. A hook was inserted in the LV to cut trabeculae. End-systolic and end-diastolic pressure-volume relationships during transient preload reduction were recorded using an admittance catheter in the following three groups: control (no cutting; n = 9), mild cutting (15 cuts; n = 5), and aggressive cutting (30 cuts; n = 5). In a second experiment, each heart served as its own control. Hemodynamic data were recorded before and after trabecular cutting ( n = 10) or sham cutting ( n = 5) within the same heart. In the first experiments, trabecular cutting did not affect systolic function ( P > 0.05) but significantly increased overall diastolic compliance ( P = 0.009). Greater compliance was seen as trabecular cutting increased ( P = 0.002, r2 = 0.435). In the second experiment, significant increases in systolic function ( P = 0.048) and diastolic compliance ( P = 0.002) were seen after trabecular cutting compared with baseline. In conclusion, trabecular cutting significantly increases diastolic compliance without reducing systolic function.

NEW & NOTEWORTHY We postulate that, in mammalian hearts, free-running trabeculae carneae exist to provide tensile support to the left ventricle and minimize diastolic wall stress. Because of hypertrophy and fibrosis of trabeculae in patients with left ventricular hypertrophy, this supportive role can become pathologic, worsening diastolic compliance. We demonstrate a novel operation involving cutting trabeculae as a method to acutely increase diastolic compliance in patients presenting with heart failure and diastolic dysfunction to improve their left ventricle compliance.
Human Papillomavirus and Coronary Artery Disease in Climacteric Women: Is There an Association?
Authors: Brito Luciane Maria Oliveira , Brito Haissa Oliveira , Corrêa Rita da Graça Carvalhal Frazão , de Oliveira Neto Clariano Pires , Costa Joyce Pinheiro Leal , Monteiro Sally Cristina Moutinho , Vidal Flávia Castello Branco , Nascimento Maria do Desterro Soares Brandão , de Figueiredo Neto José Albuquerque , Gil da Costa Rui Miguel , Galvão-Moreira Leonardo Victor , da Silva Ismael Dale Cotrim Guerreiro
Published: June 2019

Background. Cardiovascular diseases are leading causes of death worldwide. Recent studies suggest that infection by some viruses, including the human papillomavirus (HPV), may increase the risk of developing atheromatous lesions on coronary arteries. However, there is a lack of data regarding the possible association between HPV infection and coronary artery disease (CAD) in women. Objective. To investigate whether HPV infection is associated with the occurrence of CAD among climacteric women. Methods. The presence of CAD and cervical HPV DNA was investigated in 52 climacteric women. Social and demographic variables and metabolic profiles were also investigated. Results. Among 27 women with CAD, 16 were positive for HPV, whereas 11 were negative. The presence of cervical HPV was strongly associated with CAD, after adjusting for demographic variables, health and sexual behaviors, comorbidities, and known cardiovascular risk factors. HPV-positive women showed a greater likelihood of having CAD (odds ratio [OR] = 3.74; 95% confidence interval [CI]: 1.16 to 11.96) as compared with HPV-negative women, particularly those infected with high-risk HPV types (OR = 4.90; 95% CI: 1.26 to 19.08). Conclusion. These results support the hypothesis that HPV infection might be associated with CAD among climacteric women, though further studies are needed to investigate the mechanisms involved.
Newmark-FDTD Formulation for Modified Lorentz Dispersive Medium and Its Equivalence to Auxiliary Differential Equation-FDTD with Bilinear Transformation
Authors: Choi Hongjin , Cho Jeahoon , Park Yong Bae , Jung Kyung-Young
Published: June 2019

The finite-difference time-domain (FDTD) method has been popularly utilized to analyze the electromagnetic (EM) wave propagation in dispersive media. Various dispersion models were introduced to consider the frequency-dependent permittivity, including Debye, Drude, Lorentz, quadratic complex rational function, complex-conjugate pole-residue, and critical point models. The Newmark-FDTD method was recently proposed for the EM analysis of dispersive media and it was shown that the proposed Newmark-FDTD method can give higher stability and better accuracy compared to the conventional auxiliary differential equation- (ADE-) FDTD method. In this work, we extend the Newmark-FDTD method to modified Lorentz medium, which can simply unify aforementioned dispersion models. Moreover, it is found that the ADE-FDTD formulation based on the bilinear transformation is exactly the same as the Newmark-FDTD formulation which can have higher stability and better accuracy compared to the conventional ADE-FDTD. Numerical stability, numerical permittivity, and numerical examples are employed to validate our work.
Blood Pressure Variability Predicts Poor In-Hospital Outcome in Spontaneous Intracerebral Hemorrhage
Authors: Divani Afshin A. , Liu Xi , Di Napoli Mario , Lattanzi Simona , Ziai Wendy , James Michael L. , Jafarli Alibay , Jafari Mostafa , Saver Jeffrey L. , Hemphill J. Claude , Vespa Paul M. , Mayer Stephan A. , Petersen Alexander
Published: June 2019

Background and Purpose—

There is increasing evidence that higher systolic blood pressure variability (SBPV) may be associated with poor outcome in patients with intracerebral hemorrhage (ICH). We explored the association between SBPV and in-hospital ICH outcome.

Methods—

We collected 10-years of consecutive data of spontaneous ICH patients at 2 healthcare systems. Demographics, medical history, laboratory tests, computed tomography scan data, in-hospital treatments, and neurological and functional assessments were recorded. Blood pressure recordings were extracted up to 24 hours postadmission. SBPV was measured using SD, coefficient of variation, successive variation (SV), range and 1 novel index termed functional SV. The effects of SBPV on the functional outcome at discharge were evaluated by multivariate logistic and ordinal regression analyses for dichotomous and trichotomous modified Rankin Scale categorizations, respectively. In secondary analyses, associations between SBPV, history of hypertension, and hematoma expansion were explored.

Results—

The analysis included 762 subjects. All 5 SBPV indices were significantly associated with the probability of unfavorable outcome (modified Rankin Scale score, 4–6) in logistic models. In ordinal models, SD, coefficient of variation, range, and functional SV were found to have a significant effect on the probabilities of poor (modified Rankin Scale score, 3–4) and severe/death (modified Rankin Scale score, 5–6) outcomes. Normotensive patients had significantly lower mean SBPV compared with the untreated-hypertension cohort for all SBPV indices and compared with treated-hypertension patients for 3 out of 5 SBPV indices. Lower mean SBPV of treated-hypertension subjects compared with untreated-hypertension subjects was only detected in the SV and functional SV indices (
P
=0.045). None of the SBPV indices were significantly associated with the probability of hematoma expansion.

Conclusions—

Higher SBPV in the first 24 hours of admission was associated with unfavorable in-hospital outcome among ICH patients. Further prospective studies are warranted to understand any cause-effect relationship and whether controlling for SBPV may improve the ICH outcome.
References to the Coral Islands in Huang Zhong’s Hai yu 海語
Authors: Ptak Roderich
Published: June 2019

There are many studies on the history of the islands in the South China Sea. The present article looks at the references to these islands in one source, Huang Zhong’s 黄衷 Hai yu 海語 (preface 1536). This mainly concerns two entries in that work. One entry bears the title Wanli shitang 萬里石塘, the other is called Wanli changsha 萬里長沙. The article presents English translations of these entries together with detailed comments. These comments are necessary because both entries contain several terms and passages that are difficult to understand. The comments investigate questions related to the geography and other phenoma of this area. This involves citations from contemporary sources as well as from some earlier and later works. In that sense the article may classify as a long philological note, or a collection of glosses, on a particular aspect described in one important mid-Ming text.
The Sri Lankan spiny eel, Macrognathus pentophthalmos (Teleostei: Mastacembelidae), and its enigmatic decline
Authors: PETHIYAGODA ROHAN , SILVA ANJANA , MADUWAGE KALANA , KARIYAWASAM LALITH
Published: June 2019

The Sri Lankan population of the spiny eel previously assigned to Macrognathus aral Schneider (Teleostei: Mastacembelidae) is shown to be a distinct species, for which the name M. pentophthalmos Gronow is available. Macrognathus pentophthalmos is distinguished from its closest congener, M. aral, by having 14–16 dorsal spines and a pre-dorsal length of 43.3–46.8% of standard length (SL) (vs. dorsal spines 18–22 and pre-dorsal length 35.5–40.8% SL in M. aral). Macrognathus pentophthalmos differs from its only other Indian congener, M. guentheri Day, among other characters, by having 24 pairs of rostral tooth plates (vs. rostral tooth plates absent). With the present designation of a neotype, Rhynchobdella orientalis Bloch & Schneider (type locality East Indies to Sri Lanka) becomes an objective junior synonym of M. aculeatus Bloch. Although assessed as ‘common’ in 1980, the population of M. pentophthalmos suffered a precipitous decline in the following decade, the causes of which are unknown. The species may now be extinct.
Tropical and Midlatitude Impact on Seasonal Polar Predictability in the Community Earth System Model
Authors: Blanchard-Wrigglesworth Edward , Ding Qinghua
Published: June 2019

The impact on seasonal polar predictability from improved tropical and midlatitude forecasts is explored using a perfect-model experiment and applying a nudging approach in a GCM. We run three sets of 7-month long forecasts: a standard free-running forecast and two nudged forecasts in which atmospheric winds, temperature, and specific humidity (U, V, T, Q) are nudged toward one of the forecast runs from the free ensemble. The two nudged forecasts apply the nudging over different domains: the tropics (30°S–30°N) and the tropics and midlatitudes (55°S–55°N). We find that the tropics have modest impact on forecast skill in the Arctic or Antarctica both for sea ice and the atmosphere that is mainly confined to the North Pacific and Bellingshausen–Amundsen–Ross Seas, whereas the midlatitudes greatly improve Arctic winter and Antarctic year-round forecast skill. Arctic summer forecast skill from May initialization is not strongly improved in the nudged forecasts relative to the free forecast and is thus mostly a “local” problem. In the atmosphere, forecast skill improvement from midlatitude nudging tends to be largest in the polar stratospheres and decreases toward the surface.
Key Role of Cytochrome C for Apoptosis Detection Using Raman Microimaging in an Animal Model of Brain Ischemia with Insulin Treatment
Authors: Russo Vanessa , Candeloro Patrizio , Malara Natalia , Perozziello Gerardo , Iannone Michelangelo , Scicchitano Miriam , Mollace Rocco , Musolino Vincenzo , Gliozzi Micaela , Carresi Cristina , Morittu Valeria M. , Gratteri Santo , Palma Ernesto , Muscoli Carolina , Di Fabrizio Enzo , Mollace Vincenzo
Published: June 2019

Brain ischemia represents a leading cause of death and disability in industrialized countries. To date, therapeutic intervention is largely unsatisfactory and novel strategies are required for getting better protection of neurons injured by cerebral blood flow restriction. Recent evidence suggests that brain insulin leads to protection of neuronal population undergoing apoptotic cell death via modulation of oxidative stress and mitochondrial cytochrome c (CytC), an effect to be better clarified. In this work, we investigate on the effect of insulin given intracerebroventricular (ICV) before inducing a transient global ischemia by bilateral occlusion of the common carotid arteries (BCCO) in Mongolian gerbils (MG). The transient (3 min) global ischemia in MG is observed to produce neurodegenerative effect mainly into CA3 hippocampal region, 72 h after cerebral blood restriction. Intracerebroventricular microinfusion of insulin significantly prevents the apoptosis of CA3 hippocampal neurons. Histological observation, after hematoxylin and eosin staining, puts in evidence the neuroprotective role of insulin, but Raman microimaging provides a clearer insight in the CytC mechanism underlying the apoptotic process. Above all, CytC has been revealed to be an outstanding, innate Raman marker for monitoring the cells status, thanks to its resonant scattering at 530 nm of incident wavelength and to its crucial role in the early stages of cells apoptosis. These data support the hypothesis of an insulin-dependent neuroprotection and antiapoptotic mechanism occurring in the brain of MG undergoing transient brain ischemia. The observed effects occurred without any peripheral change on serum glucose levels, suggesting an alternative mechanism of insulin-induced neuroprotection.