bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebral ischemic and hemorrhagic complications of coronavirus disease 2019
Authors: Sweid Ahmad , Hammoud Batoul , Bekelis Kimon , Missios Symeon , Tjoumakaris Stavropoula I , Gooch Michael R , Herial Nabeel A , Zarzour Hekmat , Romo Victor , DePrince Maureen , Rosenwasser Robert H , Jabbour Pascal
Published: June 2020

Background

The coronavirus disease 2019 is associated with neurological manifestations including stroke.

Objectives

We present a case series of coronavirus disease 2019 patients from two institutions with acute cerebrovascular pathologies. In addition, we present a pooled analysis of published data on large vessel occlusion in the setting of coronavirus disease 2019 and a concise summary of the pathophysiology of acute cerebrovascular disease in the setting of coronavirus disease 2019.

Methods

A retrospective study across two institutions was conducted between 20 March 2020 and 20 May 2020, for patients developing acute cerebrovascular disease and diagnosed with coronavirus disease 2019. We performed a literature review using the PubMed search engine.

Results

The total sample size was 22 patients. The mean age was 59.5 years, and 12 patients were female. The cerebrovascular pathologies were 17 cases of acute ischemic stroke, 3 cases of aneurysm rupture, and 2 cases of sinus thrombosis. Of the stroke and sinus thrombosis patients, the mean National Institute of Health Stroke Scale was 13.8 ± 8.0, and 16 (84.2%) patients underwent a mechanical thrombectomy procedure. A favorable thrombolysis in cerebral infarction score was achieved in all patients. Of the 16 patients that underwent a mechanical thrombectomy, the mortality incidence was five (31.3%). Of all patients (22), three (13.6%) patients developed hemorrhagic conversion requiring decompressive surgery. Eleven (50%) patients had a poor functional status (modified Rankin Score 3–6) at discharge, and the total mortality incidence was eight (36.4%).

Conclusions

Despite timely intervention and favorable reperfusion, the mortality rate in coronavirus disease 2019 patients with large vessel occlusion was high in our series and in the pooled analysis. Notable features were younger age group, involvement of both the arterial and venous vasculature, multivessel involvement, and complicated procedures due to the clot consistency and burden.
Non-invasive Electroarthrography Measures Load-Induced Cartilage Streaming Potentials via Electrodes Placed on Skin Surrounding an Articular Joint
Authors: Changoor Adele , Garon Martin , Quenneville Eric , Bull Shelley B. , Gordon Karen , Savard Pierre , Buschmann Michael D. , Hurtig Mark B.
Published: June 2020

Objective

We aimed to demonstrate that electroarthrography (EAG) measures streaming potentials originating in the cartilage extracellular matrix during load bearing through electrodes adhered to skin surrounding an articular joint.

Design

Equine metacarpophalangeal joints were subjected to simulated physiological loads while (1) replacing synovial fluid with immersion buffers of different electrolyte concentrations and (2) directly degrading cartilage with trypsin.

Results

An inverse relationship between ionic strength and EAG coefficient was detected. Compared to native synovial fluid, EAG coefficients increased ( P < 0.05) for 5 of 6 electrodes immersed in 0.1X phosphate-buffered saline (PBS) (0.014 M NaCl), decreased ( P < 0.05) for 4 of 6 electrodes in 1X PBS (0.14 M NaCl), and decreased ( P < 0.05) for all 6 electrodes in 10X PBS (1.4 M NaCl). This relationship corresponds to similar studies where streaming potentials were directly measured on cartilage. EAG coefficients, obtained after trypsin degradation, were reduced ( P < 0.05) in 6 of 8, and 7 of 8 electrodes, during simulated standing and walking, respectively. Trypsin degradation was confirmed by direct cartilage assessments. Streaming potentials, measured by directly contacting cartilage, indicated lower cartilage stiffness ( P < 10−5). Unconfined compression data revealed reduced Em, representing proteoglycan matrix stiffness ( P = 0.005), no change in Ef, representing collagen network stiffness ( P = 0.15), and no change in permeability ( P = 0.24). Trypsin depleted proteoglycan as observed by both dimethylmethylene blue assay ( P = 0.0005) and safranin-O stained histological sections.

Conclusion

These data show that non-invasive EAG detects streaming potentials produced by cartilage during joint compression and has potential to become a diagnostic tool capable of detecting early cartilage degeneration.
Why educated youth inclined toward extremism: A case of higher education institutes of Pakistan
Authors: Ismail Muhammad , Shah Azmat Ali , Saleem Kashif , Khan Alveena
Published: June 2020

This article highlights the determinants leading to extremist behavior, i.e. the push and pull factors. The pull factors include: humanitarian causes; radical Islamic ideology; stipulation of a “purpose and mission”; propaganda through media; attraction to martyrdom; and misinterpretation of religious ideas by religious and non-religious extremists. The push factors are local conditions that force people to hold close the violent ideology of radical or extremist Islam. These comprise: local reaction against Americanization/globalization; lack of basic human rights; authoritarian/oppressive political systems; corruption/lack of meritocracy; high youth unemployment; state collapse; and porous borders. To investigate the causes of extremism in higher education institutes, Positivist philosophy (survey method) was adopted. A self-administered structured questionnaire was used to collect data from a sample of educated youth from all over Pakistan, collected via the probability sampling technique. It was revealed that ‘Promotion of Martyrdom’ was highly correlated with extremism, and contributed more than other variables to causing extremism.
Cap-assisted endoscopic sclerotherapy for internal hemorrhoids: technique protocol and study design for a multi-center randomized controlled trial
Authors: Wu Xia , Wen Quan , Cui Bota , Liu Yafei , Zhong Min , Yuan Yu , Wu Lihao , Zhang Xiaoyin , Hu Yunlian , Lv Muhan , Wu Qianneng , He Suyu , Jin Yan , Tian Shuxin , Wan Rong , Wang Xin , Xu Long , Bai Jianling , Huang Guangming , Ji Guozhong , Zhang Faming
Published: June 2020

Background:

Cap-assisted endoscopic sclerotherapy is a new interventional therapy for internal hemorrhoids and rectal prolapse under colonoscopy. The proper length of the endoscopic injection needle is the core for performing cap-assisted endoscopic sclerotherapy well with more benefits and less complications. However, no data are currently available to guide endoscopists to consider the length of injection needle before cap-assisted endoscopic sclerotherapy. This study is designed to evaluate the efficacy and safety of cap-assisted endoscopic sclerotherapy with long or short injection needle in the treatment of internal hemorrhoids.

Methods:

This is a nationwide multi-center, prospective, single-blind and randomized controlled trial. Patients with grade I-II internal hemorrhoids who have failed to conservative treatments and grade III internal hemorrhoids who are not suitable for surgery or refuse surgery will be included. Participants will be randomized 1:1 into either long or short injection needle group. The primary outcome is the recurrence rate of internal hemorrhoids 24 weeks after cap-assisted endoscopic sclerotherapy. The secondary outcomes are as follows: (1) symptom severity score, (2) three-level EuroQoL five dimensions health scale scores, (3) occurrence of adverse events and severe adverse events, and (4) patients’ attitudes toward cap-assisted endoscopic sclerotherapy. Data collection will be conducted before and during operation, the 1st day, 1st week, 2nd week, and 24th week after cap-assisted endoscopic sclerotherapy.

Discussion:

The outcome of this study is expected to provide a practical clinical protocol of cap-assisted endoscopic sclerotherapy for patients with internal hemorrhoids and promote the use of this new endoscopic technique.

Trial registration:

ClinicalTrials.gov, NCT03917056. Registered on 12 April 2019.
Dynamic Modeling and Analysis of 5-PSS/UPU Parallel Mechanism with Elastically Active Branched Chains
Authors: Li Yanbiao , Zheng Hang , Chen Bo , Sun Peng , Wang Zesheng , Shuai Kun , Yue Yi
Published: June 2020

To study the characteristics of the 5-prismatic–spherical–spherical (PSS)/universal–prismatic–universal (UPU) parallel mechanism with elastically active branched chains, the dynamics modeling and solutions of the parallel mechanism were investigated. First, the active branched chains and screw sliders were considered as spatial beam elements and plane beam element models, respectively, and the dynamic equations of each element model were derived using the Lagrange method. Second, the equations of the 5-PSS/UPU parallel mechanism were obtained according to the kinematic coupling relationship between the active branched chains and moving platform. Finally, based on the parallel mechanism dynamic equations, the natural frequency distribution of the 5-PSS/UPU parallel mechanism in the working space and elastic displacement of the moving platform were obtained. The results show that the natural frequency of the 5-PSS/UPU parallel mechanism under a given motion situation is greater than its operating frequency. The maximum position error is − 0.096 mm in directionY, and the maximum orientation error is − 0.29° around theX-axis. The study provides important information for analyzing the dynamic performance, dynamic optimization design, and dynamic control of the 5-PSS/UPU parallel mechanism with elastically active branched chains.
Short-term efficacy and safety of lasmiditan, a novel 5-HT1F receptor agonist, for the acute treatment of migraine: a systematic review and meta-analysis
Authors: Hou Min , Xing Haiyan , Li Chen , Wang Xianfeng , Deng Dongmei , Li Juan , Zhang Pan , Chen Jianhong
Published: June 2020

Background

Migraine has been recognized as one of common diseases in the world whose current treatment options are not ideal. Lasmiditan, an oral 5-hydroxytryptamine (HT)1Freceptor agonist, appears more promising for the acute treatment of migraine because of considerably better effect profiles with no severe adverse events (AEs). This review aimed to systematically evaluate the efficacy and safety of lasmiditan from the results of randomized controlled trials (RCTs).

Methods

PubMed, Cochrane Library, Embase were searched on lasmiditan for the acute treatment of migraine from inception of the databases to Feb 1, 2020. Pain free and pain relief, global impression (very much/much better), and no/mild disability at 2 h in efficacy; total treatment-emergent adverse events (TEAEs), dizziness, nausea, fatigue, paraesthesia and somnolence in safety were extracted from the included studies. A systematic review and meta-analysis was performed using Review Manager Software version 5.3 (RevMan 5.3).

Results

Four RCTs with a total of 4960 subjects met our inclusion criteria. The overall effect estimate showed that lasmiditan was significantly superior to placebo in terms of pain free (RR 1.71, 95% CI 1.55–1.87), pain relief (RR 1.40, 95% CI 1.33–1.47), global impression (very much/much better) (RR 1.55, 95% CI 1.44–1.67), and no/mild disability (RR 1.15, 95% CI 1.10–1.20) at 2 h. For the safety, significant number of patients experienced TEAEs with lasmiditan than with placebo (RR 2.77, 95% CI 2.53–3.03), most TEAEs were central nervous system (CNS)-related and included dizziness (RR 5.81, 95% CI 4.72–7.14), nausea (RR 2.58, 95% CI 1.87–3.57), fatigue (RR 5.38, 95% CI 3.78–7.66), paraesthesia (RR 4.48, 95% CI 3.33–6.02), and somnolence (RR 2.82, 95% CI 2.18–3.66).

Conclusions

This meta-analysis suggests that lasmiditan is effective for the acute treatment of migraine with a higher incidence of CNS-related adverse reactions compared with placebo. Long-term, open-label, multi-dose trials are required to verify the current findings.
A comprehensive systematic review of CSF proteins and peptides that define Alzheimer’s disease
Authors: Pedrero-Prieto Cristina M. , García-Carpintero Sonia , Frontiñán-Rubio Javier , Llanos-González Emilio , Aguilera García Cristina , Alcaín Francisco J. , Lindberg Iris , Durán-Prado Mario , Peinado Juan R. , Rabanal-Ruiz Yoana
Published: June 2020

Background

During the last two decades, over 100 proteomics studies have identified a variety of potential biomarkers in CSF of Alzheimer’s (AD) patients. Although several reviews have proposed specific biomarkers, to date, the statistical relevance of these proteins has not been investigated and no peptidomic analyses have been generated on the basis of specific up- or down- regulation. Herein, we perform an analysis of all unbiased explorative proteomics studies of CSF biomarkers in AD to critically evaluate whether proteins and peptides identified in each study are consistent in distribution; direction change; and significance, which would strengthen their potential use in studies of AD pathology and progression.

Methods

We generated a database containing all CSF proteins whose levels are known to be significantly altered in human AD from 47 independent, validated, proteomics studies. Using this database, which contains 2022 AD and 2562 control human samples, we examined whether each protein is consistently present on the basis of reliable statistical studies; and if so, whether it is over- or under-represented in AD. Additionally, we performed a direct analysis of available mass spectrometric data of these proteins to generate an AD CSF peptide database with 3221 peptides for further analysis.

Results

Of the 162 proteins that were identified in 2 or more studies, we investigated their enrichment or depletion in AD CSF. This allowed us to identify 23 proteins which were increased and 50 proteins which were decreased in AD, some of which have never been revealed as consistent AD biomarkers (i.e. SPRC or MUC18). Regarding the analysis of the tryptic peptide database, we identified 87 peptides corresponding to 13 proteins as the most highly consistently altered peptides in AD. Analysis of tryptic peptide fingerprinting revealed specific peptides encoded by CH3L1, VGF, SCG2, PCSK1N, FBLN3 and APOC2 with the highest probability of detection in AD.

Conclusions

Our study reveals a panel of 27 proteins and 21 peptides highly altered in AD with consistent statistical significance; this panel constitutes a potent tool for the classification and diagnosis of AD.
Critical relationships in managing students’ emotional responses to science (and evolution) instruction
Authors: Scharmann Lawrence C. , Grauer Bette L.
Published: June 2020

Background

If an instructional environment that is conducive to learning generally requires the development of good student–teacher relationships, then a classroom atmosphere of trust is an especially important consideration when we engage students in the teaching and learning of evolution. Emotional scaffolding, therefore, is crucial to the successful teaching and learning of evolution. Quinlan (Coll Teach 64:101–111, 2016) refers to four key relationships necessary to construct this scaffolding—students with teachers being merely one of the four key relationships comprising a comprehensive emotional scaffolding—the others being students with subject matter, students with other students, and students with their developing selves. Our purpose here is to examine the types of student emotional responses that secondary science teachers reported as emerging in their science classes and categorize students’ behavioral responses as being representative of the four key relationships, identified by Quinlan (Coll Teach 64:101–111, 2016), as necessary for promoting both enhanced learning and individual student growth.

Results

The results of this current study are highly encouraging in that respect. Each of the eight teachers were able to identify the development of each of the four key relationships identified by Quinlan as crucial for instructional success. In addition, where individual teacher profiles were statistically different than the aggregate profile across all eight teachers, it was due to a trade-off in emphasis of the development of one relationship in preference to another.

Conclusion

The most salient recommendations to manage emotional responses to evolution instruction are to: (1) Foster relationships that engage students in positive conversations; (2) Construct relationships in an appropriate sequence—Teacher–Student and Subject–Student first, followed by student–student and finally nurturing students with developing selves; (3) Use non-threatening assessments; and (4) Allow students to privately express their honest feelings about the science being learned.
Matrix factorization with neural network for predicting circRNA-RBP interactions
Authors: Wang Zhengfeng , Lei Xiujuan
Published: June 2020

Background

Circular RNA (circRNA) has been extensively identified in cells and tissues, and plays crucial roles in human diseases and biological processes. circRNA could act as dynamic scaffolding molecules that modulate protein-protein interactions. The interactions between circRNA and RNA Binding Proteins (RBPs) are also deemed to an essential element underlying the functions of circRNA. Considering cost-heavy and labor-intensive aspects of these biological experimental technologies, instead, the high-throughput experimental data has enabled the large-scale prediction and analysis of circRNA-RBP interactions.

Results

A computational framework is constructed by employing Positive Unlabeled learning (P-U learning) to predict unknown circRNA-RBP interaction pairs with kernel model MFNN (Matrix Factorization with Neural Networks). The neural network is employed to extract the latent factors of circRNA and RBP in the interaction matrix, the P-U learning strategy is applied to alleviate the imbalanced characteristics of data samples and predict unknown interaction pairs. For this purpose, the known circRNA-RBP interaction data samples are collected from the circRNAs in cancer cell lines database (CircRic), and the circRNA-RBP interaction matrix is constructed as the input of the model. The experimental results show that kernel MFNN outperforms the other deep kernel models. Interestingly, it is found that the deeper of hidden layers in neural network framework does not mean the better in our model. Finally, the unlabeled interactions are scored using P-U learning with MFNN kernel, and the predicted interaction pairs are matched to the known interactions database. The results indicate that our method is an effective model to analyze the circRNA-RBP interactions.

Conclusion

For a poorly studied circRNA-RBP interactions, we design a prediction framework only based on interaction matrix by employing matrix factorization and neural network. We demonstrate that MFNN achieves higher prediction accuracy, and it is an effective method.
BMI differences among in-hospital management and outcomes in patients with atrial fibrillation: findings from the Care for Cardiovascular Disease project in China
Authors: Deng Fuxue , Zhang Yan , Zhao Qiang , Deng Yangyang , Gao Shanshan , Zhang Lisha , Dong Mengya , Yuan Zuyi , Lei Xinjun ,   on behalf of the CCC-AF investigators
Published: June 2020

Background

Underweight or obese status influences the prognosis of atrial fibrillation (AF). However, the association between stratification of body mass index (BMI) and in-hospital outcomes in patients with AF, remains lacking in China.

Methods

Using data from the Improving Care for Cardiovascular Disease in China-AF project, which was launched in February 2015 and recruited 150 hospitals in China, we compared characteristics, in-hospital treatments and clinical outcomes among the stratifications of BMI for Asians.

Results

A total of 15,867 AF patients with AF were enrolled, including 830 (5.23%) underweight, 4965 (31.29%) with normal weight, 3716 (23.42%) overweight, 5263 (33.17%) obese class I and 1093 (6.89%) obese class II participants. Compared with normal weight patients, underweight, overweight, and obese patients showed increased percentages of CHADS2 scores (3–6) and CHA2DS2-VASc scores (5–9). During hospitalization, overweight or obese patients showed greater use of rhythm control medications, anticoagulant drugs, and intervention therapies than underweight–normal weight patients. In adjusted logistic models, BMI was a strong predictor of in-hospital mortality. Especially, underweight BMI was associated with higher incidence of in-hospital mortality, with an adjusted odds ratio of 2.08 (95% confidence interval, 1.56–4.46; p = 0.04) than overweight and obese BMI.

Conclusions

Asian patients with AF and high BMI received more medical treatments and presented less adverse in-hospital outcomes compared with those with underweight–normal weight. Although low BMI may be associated with other comorbidities and advanced age, underweight BMI retained a negative correlation with all-cause mortality in the patients with AF during hospitalization.
Recent trends and variations in general practitioners’ involvement in accident care in Switzerland: an analysis of claims data
Authors: Höglinger Marc , Knöfler Fabio , Schaumann-von Stosch Rita , Scholz-Odermatt Stefan M. , Eichler Klaus
Published: June 2020

Abstract/summary

Background

As in other countries, there is concern and some fragmentary evidence that GPs’ central role in the Swiss healthcare system as the primary provider of care might be changing or even be in decline. Our study gives a systematic account of GPs’ involvement in accident care from 2008 to 2016 and identifies changes in GPs’ involvement in this typical field of primary care: how frequently GPs were involved along the care pathway, to what extent they figured as initial care provider, and what their role in the care pathway was.

Methods

Using a claims dataset from the largest Swiss accident insurer with two million accident cases, we constructed individual care pathways, i.e., when and from which providers patients received care. We calculated probabilities for the involvement of various care provider groups, for initial care provision, and for the role of GPs in patients’ care pathways, adjusted for injury and patient characteristics using multinomial regression.

Results

In 2014, GPs were involved in 70% of all accident cases requiring outpatient care but no inpatient stay, and provided initial care in 56%. While involvement stayed at about the same level for accidents occurring from 2008 to 2014, the share of accidents where GPs provided initial care decreased by 4 percentage points. The share of cases where GPs acted as sole care provider decreased by 7 percentage points down to 44%. At the same time, accident cases involving care from an ED at any point in time increased from 38 to 46% and the share receiving initial care from an ED from 30 to 35 percentage points – apparently substituting for the declining involvement of GPs in initial care. GPs’ involvement in accident care is higher in rural compared to urban regions, among elderly compared to younger patients, and among Swiss compared to non-Swiss citizens.

Conclusions

GPs play a key role in accident care with considerable variation depending on region and patient profile. From 2008 to 2014, there is a remarkable decline in GPs’ provision of initial care after an accident. This is a strong indication that the GPs’ role in the Swiss healthcare system is changing.
Percutaneous stent placement for malignant hilar biliary obstruction: side-by-side versus stent-in-stent technique
Authors: Zhou Wei-Zhong , Liu Sheng , Yang Zheng-Qiang , Xian Yu-Tao , Xu Hong-dou , Wu Jun-zheng , Shi Hai-Bin
Published: June 2020

Background

Currently, side-by-side (SBS) and stent-in-stent (SIS) are the two main techniques for stent deployment to treat hilar biliary obstructions. Previous studies comparing these two techniques are very limited, and thus, no consensus has been reached on which technique is better. The purpose of this study is to compare the clinical efficacy and safety of SBS and SIS deployment via a percutaneous approach for malignant hilar biliary obstruction.

Methods

From July 2012 to April 2019, 65 patients with malignant hilar biliary obstruction who underwent bilateral stenting using either the SBS or SIS techniques were included in this study. Among them, 27 patients underwent SIS stent insertion (SIS group), and the remaining 38 patients underwent SBS stent insertion (SBS group). Technical success, improvement of jaundice, complications, duration of stent patency, and overall survival were evaluated.

Results

Technical success was achieved in all patients in the two groups. The serum bilirubin level decreased more rapidly 1 week after the procedures in the SBS group than in the SIS group (P = 0.02). Although the total complication rate did not differ between the two groups, cholangitis was found to be more frequent in the SIS group (P = 0.04). The median stent patency was significantly longer in the SBS group (149 days) than in the SIS group (75 days; P = 0.02). The median overall survival did not significantly differ between the two groups (SBS vs. SIS, 155 days vs. 143 days; P > 0.05).

Conclusions

Percutaneous transhepatic bilateral stenting using either the SBS or SIS technique is safe and effective in the management of malignant hilar biliary obstruction. However, SBS offers a quicker improvement of jaundice, a lower incidence of cholangitis after the procedure, and a longer stent patency period than SIS.
Use of Immunostaining for the diagnosis of Lymphovascular invasion in superficial Barrett’s esophageal adenocarcinoma
Authors: Hosono Isao , Miyahara Ryoji , Furukawa Kazuhiro , Funasaka Kohei , Sawada Tsunaki , Maeda Keiko , Yamamura Takeshi , Ishikawa Takuya , Ohno Eizaburo , Nakamura Masanao , Kawashima Hiroki , Yokoi Takio , Tsukamoto Tetsuya , Hirooka Yoshiki , Fujishiro Mitsuhiro
Published: June 2020

Background

The prevalence of Barrett’s esophageal adenocarcinoma (BEA) is increasing in Japan. Accurate assessment of lymphovascular invasion (LVI) after endoscopic resection or surgery is essential in evaluating treatment response. This study aimed to assess the usefulness of immunostaining in determining the extent of LVI in superficial BEA.

Methods

We retrospectively included 41 patients who underwent endoscopic resection or surgery between January 2007 and July 2018. In all cases, 3-μm serial sections from paraffin-embedded resected specimens were used for hematoxylin and eosin (H-E) staining and immunostaining for D2–40 and CD31. Two specialized gastrointestinal pathologists (T.Y. and T.T.), blinded to clinical information, independently evaluated the extent of LVI from these specimens. The LVI-positivity rate was evaluated with respect to the depth of invasion, changes in the positivity rate on immunostaining, pathological characteristics of patients with LVI, lymph node metastasis or relapse, and course after treatment.

Results

H-E staining alone identified LVI in 7 patients (positivity rate: 17.1%). Depths of invasion were categorized based on extension to the submucosa (SM) or deeper. On immunostaining for D2–40 and CD31, additional positivity was detected in 2 patients with SM1 and 1 SM3, respectively; LVI was detected in 10 patients (positivity rate: 24.4%). LVI-positivity rates with invasion of the superficial muscularis mucosa (SMM)/lamina propria mucosa (LPM)/deep muscularis mucosa (DMM), SM 1, 2, and 3 were 0, 75, 28.6, and 55.6%, respectively.

Conclusions

Combined H-E staining and immunostaining is useful in diagnosing LVI in superficial BEA, particularly in endoscopically resected specimens.
Perceived risks, concession travel pass access and everyday technology use for out-of-home participation: cross-sectional interviews among older people in the UK
Authors: Gaber Sophie Nadia , Nygård Louise , Kottorp Anders , Charlesworth Georgina , Wallcook Sarah , Malinowsky Camilla
Published: June 2020

Background

The health-promoting qualities of participation as an opportunity for social and cognitive engagement are well known. Use of Everyday Technology such as Smartphones or ATMs, as enabling or disabling factors for out-of-home participation is however under-researched, particularly among older people with and without dementia. Out-of-home participation involves participation in places and activities outside of a person’s home, in public space. Situated within the context of an increasingly technological society, the study investigated factors such as perceived risks, access to a concession travel pass and use of Everyday Technologies, and their relationship with out-of-home participation, among older people in the UK.

Methods

One hundred twenty-eight older people with and without dementia in urban and rural environments in the UK, were interviewed using the Participation in ACTivities and Places OUTside Home (ACT-OUT) Questionnaire and the Everyday Technology Use Questionnaire (ETUQ). Associations between Everyday Technology use, perceived risk of falling, functional impairment, access to a concession travel pass and out-of-home participation were investigated using ordinal regression.

Results

A higher probability of Everyday Technology use (Odds Ratio [OR] = 1.492; 95% Confidence Interval [CI] = 1.041–1.127), perceived risk of falling outside home (OR = 2.499; 95% CI = 1.235–5.053) and, access to a concession travel pass (OR = 3.943; 95% CI = 1.970–7.893) were associated with a higher level of out-of-home participation. However, other types of risk (getting lost; feeling stressed or embarrassed) were not associated with out-of-home participation. Having a functional impairment was associated with a low probability of a higher level of out-of-home participation (OR = .470; 95% CI = .181–1.223). Across the sample, ‘outside home’ Everyday Technologies were used to a higher degree than ‘portable’ Everyday Technologies which can be used both in and outside home.

Conclusions

The study provides insights into perceived risks, access to a concession travel pass and use of Everyday Technologies, and their relationship with out-of-home participation, among older people in the UK. Increased knowledge about factors associated with out-of-home participation may help to guide targeted health and social care planning.
Association between walking 5000 step/day and fall incidence over six months in urban community-dwelling older people
Authors: Aranyavalai T. , Jalayondeja C. , Jalayondeja W. , Pichaiyongwongdee S. , Kaewkungwal J. , Laskin J. J.
Published: June 2020

Background

Walking is the most common population-wide campaign for health promotion in older people. However, the cutoff threshold for walking steps/day to identify the older people who are at risk of falling is not recommended. Therefore, the objectives were to investigate the association between all possible risk factors including physical performance, physical activity and fall incidence over the six-month in community-dwelling older people who had low-risk of falling and to identify walking threshold (steps/day) for reducing risk of fall.

Methods

The older people who aged ≥60 years and had free of falling for 1 year were invited to participate in this study. They lived in five communities in Bangkok Thailand. Demographics and physical performances were collected at baseline. Walking (step/day) and 24-h physical activity (PA) were monitored for 5 consecutive days by the Actical® accelerometer wrapped on non-dominant wrists. The Physical Activity Scale for the Elderly (PASE) questionnaire was used to record activities in the past 7 days by interview. A monthly calendar was used to record fall incidence over the 6 months. Unadjusted and adjusted hazard ratio (HR) with 95% confidence interval (CI) were analyzed using the Cox’s proportional hazard regression. The Kaplan Meier curve illustrated the probability to survive from fall over the 6 months.

Results

Of 255, 33 older people (12.94%) reported first-fall incidence over the 6 months. Fall incidence density rate was 0.79 per 1000 person-day. Our findings showed that significant association between fall incidence and behavioral risk factors including PASE scores < 100 (HR = 3.53; 95% CI: 1.24–10.04), walking < 5000 steps/day (HR = 3.6; 95% CI: 1.76–7.31) and moderate to vigorous intensity of PA at < 60 min/week (HR = 3.66; 95% CI: 1.12–12.01). Fall incidence were related to the following risk factors: age (HR = 3.54; 95% CI: 1.37–9.11), took polypharmacy/antipsychotics (HR = 4.32; 95% CI: 2.12–8.79), presence of urinary incontinence (HR = 2.87; 95% CI: 1.45–5.68), low functional mobility by Timed Up and Go ≥13.5 s (HR = 6.43; 95% CI: 2.65–15.57).

Conclusions

This study proposed walking ≥5000 steps/day as a cutoff threshold to recommend for reducing risk of falling in community-dwelling older people who had low-risk of falling.
The association between a fracture risk tool and frailty: Geelong Osteoporosis Study
Authors: Tembo Monica C. , Holloway-Kew Kara L. , Mohebbi Mohammadreza , Sui Sophia X. , Hosking Sarah M. , Brennan-Olsen Sharon L. , Williams Lana J. , Kotowicz Mark A. , Pasco Julie A.
Published: June 2020

Background

Frailty is characterised by age-related declines in physical, psychological and social functioning. Features of frailty overlap with risk factors for fragility fractures. The aim of this study was to investigate the association between the fracture risk assessment tool (FRAX®) and frailty.

Methods

In cross-sectional analysis, frailty status was determined for participants aged 60-90 yr at 15-year follow-up of the Geelong Osteoporosis Study, using a modified Fried frailty phenotype. Using the FRAX on-line tool, scores for hip and major osteoporotic fracture (MOF) were calculated with and without bone mineral density (BMD). Using the area under Receiver Operating Characteristic (AUROC) curves, and FRAX scores calculated at the baseline visit for these participants, we investigated the association of FRAX and frailty 15 years later.

Results

Forty-seven of 303 women (15.5%) and 41 of 282 men (14.5%) were frail at the 15-year visit. There was a gradient of increasing median FRAX scores from robust to frail. For example, for women, median MOF-FRAX without BMD increased from 5.9 for the robust to 7.5 for the pre-frail and 14.0 for the frail (p < 0.001). In secondary analyses, an association was observed between FRAX and frailty over 15 years, with the highest AUROC for women being 0.72 for MOF-FRAX with BMD, and for men, 0.76 hip-FRAX without BMD.

Conclusion

An association was observed between FRAX and frailty where frail men and women had higher FRAX-scores compared to the other groups. Preliminary data suggest that FRAX, with or without BMD, may be useful in enhancing the information on frailty. Further research using larger datasets will be required to explore this.
Canine serological survey and dog culling and its relationship with human visceral leishmaniasis in an endemic urban area
Authors: Bermudi Patricia Marques Moralejo , Costa Danielle Nunes Carneiro Castro , Nunes Caris Maroni , Tolezano Jose Eduardo , Hiramoto Roberto Mitsuyoshi , Rodas Lilian Aparecida Colebrusco , Cipriano Rafael Silva , Blangiardo Marta , Chiaravalloti-Neto Francisco
Published: June 2020

Background

Visceral leishmaniasis is an important but neglected disease that is spreading and is highly lethal when left untreated. This study sought to measure the Leishmania infantum seroprevalence in dogs, the coverage of its control activities (identification of the canine reservoir by serological survey, dog culling and insecticide spraying) and to evaluate its relationship with the occurrence of the disease in humans in the municipalities of Araçatuba and Birigui, state of São Paulo, Brazil.

Methods

Information from 2006 to 2015 was georeferenced for each municipality and modeling was performed for the two municipalities together. To do this, latent Gaussian Bayesian models with the incorporation of a spatio-temporal structure and Poisson distribution were used. The Besag-York-Mollie models were applied for random spatial effects, as also were autoregressive models of order 1 for random temporal effects. The modeling was performed using the INLA (Integrated Nested Laplace Approximations) deterministic approach, considering both the numbers of cases as well as the coverage paired year by year and lagged at one and two years.

Results

Control activity coverage was observed to be generally low. The behavior of the temporal tendency in the human disease presented distinct patterns in the two municipalities, however, in both the tendency was to decline. The canine serological survey presented as a protective factor only in the two-year lag model.

Conclusions

The canine serological coverage, even at low intensity, carried out jointly with the culling of the positive dogs, suggested a decreasing effect on the occurrence of the disease in humans, whose effects would be seen two years after it was carried out.
Effectiveness and tolerability of intravenous pentamidine for Pneumocystis carinii pneumonia prophylaxis in adult hematopoietic stem cell transplant patients: a retrospective study
Authors: Awad Wedad B. , Asaad Alaa , Al-Yasein Nardin , Najjar Rula
Published: June 2020

Background

Pneumocystis cariniipneumonia (PCP) prophylaxis is recommended after hematopoietic stem cell transplantation (HSCT). In patients who are unable to take first-line prophylaxis, trimethoprim/sulfamethoxazole, aerosolized pentamidine is recommended. This drug may not, however, be available at all institutions, and its administration requires special techniques. Therefore, intravenous pentamidine (IVP) has been used in adult patients as an alternative, despite limited data. We evaluated the effectiveness and tolerability of IVP for PCP prophylaxis in adult patients who had undergone HSCT.

Methods

A single-center retrospective study was conducted of adult patients who had undergone allogenic or autologous HSCT between January 2014 and September 2018 and had received at least three doses of IVP for PCP prophylaxis. The IVP dose was 4 mg/kg administered monthly. Data on PCP infection and adverse reactions were collected from both patients’ electronic medical records and the pharmacy adverse drug reactions documentation system. Patients were followed from the start of IVP up to 6 months after discontinuation of therapy. A confirmed PCP infection was defined as radiographic evidence of PCP and positive staining of a respiratory specimen. Descriptive statistics were used to analyze the study outcomes.

Results

During the study period, 187 patients were included. The median age was 36.4 years (range, 18–64), 58% were male, and 122 (65%) had received allogeneic HSCT while the remainder autologous HSCT. The median number of IVP doses administered per patient was 5 (range, 3–29). During the study period, none of the patients had evidence of confirmed PCP infection. However; there were two cases with high clinical suspicion of PCP infection (i.e. required anti-pneumocystis therapy) and one reported case of central nervous system toxoplasmosis while receiving IVP for PCP prophylaxis. Only one case of nausea associated with IVP administration was reported.

Conclusions

In a cohort of adult patients with HSCT who received IVP for PCP prophylaxis, there was no evidence of confirmed PCP infection, and the treatment appeared to be well tolerated. Prospective studies should be conducted to confirm the efficacy and tolerability of IVP.
Identifying genetic variants and pathways associated with extreme levels of fetal hemoglobin in sickle cell disease in Tanzania
Authors: Nkya Siana , Mwita Liberata , Mgaya Josephine , Kumburu Happiness , van Zwetselaar Marco , Menzel Stephan , Mazandu Gaston Kuzamunu , Sangeda Raphael , Chimusa Emile , Makani Julie
Published: June 2020

Background

Sickle cell disease (SCD) is a blood disorder caused by a point mutation on the beta globin gene resulting in the synthesis of abnormal hemoglobin. Fetal hemoglobin (HbF) reduces disease severity, but the levels vary from one individual to another. Most research has focused on common genetic variants which differ across populations and hence do not fully account for HbF variation.

Methods

We investigated rare and common genetic variants that influence HbF levels in 14 SCD patients to elucidate variants and pathways in SCD patients with extreme HbF levels (≥7.7% for high HbF) and (≤2.5% for low HbF) in Tanzania. We performed targeted next generation sequencing (Illumina_Miseq) covering exonic and other significant fetal hemoglobin-associated loci, including BCL11A, MYB, HOXA9, HBB, HBG1, HBG2, CHD4, KLF1, MBD3, ZBTB7A and PGLYRP1.

Results

Results revealed a range of genetic variants, including bi-allelic and multi-allelic SNPs, frameshift insertions and deletions, some of which have functional importance. Notably, there were significantly more deletions in individuals with high HbF levels (11% vs 0.9%). We identified frameshift deletions in individuals with high HbF levels and frameshift insertions in individuals with low HbF. CHD4 and MBD3 genes, interacting in the same sub-network, were identified to have a significant number of pathogenic or non-synonymous mutations in individuals with low HbF levels, suggesting an important role of epigenetic pathways in the regulation of HbF synthesis.

Conclusions

This study provides new insights in selecting essential variants and identifying potential biological pathways associated with extreme HbF levels in SCD interrogating multiple genomic variants associated with HbF in SCD.
Quality use of medicines in patients with chronic kidney disease
Authors: Castelino Ronald L. , Saunder Timothy , Kitsos Alex , Peterson Gregory M. , Jose Matthew , Wimmer Barbara , Khanam Masuma , Bezabhe Woldesellassie , Stankovich Jim , Radford Jan
Published: June 2020

Background

Chronic kidney disease (CKD) affects drug elimination and patients with CKD require appropriate adjustment of renally cleared medications to ensure safe and effective pharmacotherapy. The main objective of this study was to determine the extent of potentially inappropriate prescribing (PIP; defined as the use of a contraindicated medication or inappropriately high dose according to the kidney function) of renally-cleared medications commonly prescribed in Australian primary care, based on two measures of kidney function. A secondary aim was to assess agreement between the two measures.

Methods

Retrospective analysis of routinely collected de-identified Australian general practice patient data (NPS MedicineWise MedicineInsight from January 1, 2013, to June 1, 2016; collected from 329 general practices). All adults (aged ≥18 years) with CKD presenting to general practices across Australia were included in the analysis. Patients were considered to have CKD if they had two or more estimated glomerular filtration rate (eGFR) recorded values < 60 mL/min/1.73m2, and/or two urinary albumin/creatinine ratios ≥3.5 mg/mmol in females (≥2.5 mg/mmol in males) at least 90 days apart. PIP was assessed for 49 commonly prescribed medications using the Cockcroft-Gault (CG) equation/eGFR as per the instructions in the Australian Medicines Handbook.

Results

A total of 48,731 patients met the Kidney Health Australia (KHA) definition for CKD and had prescriptions recorded within 90 days of measuring serum creatinine (SCr)/estimated glomerular filtration rate (eGFR). Overall, 28,729 patients were prescribed one or more of the 49 medications of interest. Approximately 35% (n = 9926) of these patients had at least one PIP based on either the Cockcroft-Gault (CG) equation or eGFR (CKD-EPI; CKD-Epidemiology Collaboration Equation). There was good agreement between CG and eGFR while determining the appropriateness of medications, with approximately 97% of the medications classified as appropriate by eGFR also being considered appropriate by the CG equation.

Conclusion

This study highlights that PIP commonly occurs in primary care patients with CKD and the need for further research to understand why and how this can be minimised. The findings also show that the eGFR provides clinicians a potential alternative to the CG formula when estimating kidney function to guide drug appropriateness and dosing.
The initial engraftment of tumor cells is critical for the future growth pattern: a mathematical study based on simulations and animal experiments
Authors: Hoffmann Bertin , Lange Tobias , Labitzky Vera , Riecken Kristoffer , Wree Andreas , Schumacher Udo , Wedemann Gero
Published: June 2020

Background

Xenograft mouse tumor models are used to study mechanisms of tumor growth and metastasis formation and to investigate the efficacy of different therapeutic interventions. After injection the engrafted cells form a local tumor nodule. Following an initial lag period of several days, the size of the tumor is measured periodically throughout the experiment using calipers. This method of determining tumor size is error prone because the measurement is two-dimensional (calipers do not measure tumor depth). Primary tumor growth can be described mathematically by suitable growth functions, the choice of which is not always obvious. Growth parameters provide information on tumor growth and are determined by applying nonlinear curve fitting.

Methods

We used self-generated synthetic data including random measurement errors to research the accuracy of parameter estimation based on caliper measured tumor data. Fit metrics were investigated to identify the most appropriate growth function for a given synthetic dataset. We studied the effects of measuring tumor size at different frequencies on the accuracy and precision of the estimated parameters. For curve fitting with fixed initial tumor volume, we varied this fixed initial volume during the fitting process to investigate the effect on the resulting estimated parameters. We determined the number of surviving engrafted tumor cells after injection using ex vivo bioluminescence imaging, to demonstrate the effect on experiments of incorrect assumptions about the initial tumor volume.

Results

To select a suitable growth function, measurement data from at least 15 animals should be considered. Tumor volume should be measured at least every three days to estimate accurate growth parameters. Daily measurement of the tumor volume is the most accurate way to improve long-term predictability of tumor growth. The initial tumor volume needs to have a fixed value in order to achieve meaningful results. An incorrect value for the initial tumor volume leads to large deviations in the resulting growth parameters.

Conclusions

The actual number of cancer cells engrafting directly after subcutaneous injection is critical for future tumor growth and distinctly influences the parameters for tumor growth determined by curve fitting.