bluuebunny/crossref_metadata_2025 huggingface dataset:
Lnc-ATG9B-4 aggravates progress of hepatocellular carcinoma through cell proliferation and migration by upregulating CDK5
Authors: Li Ming , Wei Le , Liu Pin-Yue , Zhang Xue-Mei , Liu Fang , Yang Fen , Hu Xiang-Shang , Mo Zhong-Cheng
Published: October 2020

Long noncoding RNAs play an important role in the occurrence, invasion, as well as metastasis of various human cancers, including hepatocellular carcinoma. Long noncoding RNAs can affect the biological functions of hepatocellular carcinoma cells by regulating various genes; however, only a small fraction of molecular mechanisms of long noncoding RNAs have been elucidated. In the present study, lnc AC010973.1 (lnc-ATG9B-4) was first identified by microarray analysis from 8 patients with hepatocellular carcinoma and confirmed by quantitative PCR in 176 patients with hepatocellular carcinoma. We demonstrated that lnc-ATG9B-4 was tightly relative to the tumorous size, TNM stages, portal vein tumor thrombus (PVTT), the tumor capsule, metastasis, degree of differentiation, and poor prognosis of hepatocellular carcinoma according to long-term follow-up data. In hepatocellular carcinoma cells, overexpression of lnc-ATG9B-4 promoted proliferation, invasion, as well as migration, while inhibiting lnc-ATG9B-4 by siRNA significantly attenuated the proliferation, invasion, as well as migration. Interestingly, lnc-ATG9B-4 increased the expression of cyclin-dependent kinase 5 (CDK5), which was closely related to the development and chemotherapy sensitivity of hepatocellular carcinoma. In summary, our results revealed that lnc-ATG9B-4 suggests an unfavorable prognosis of hepatocellular carcinoma and facilitates the proliferation, invasion, as well as migration of hepatocellular carcinoma cells by upregulating CDK5. This research suggests that lnc-ATG9B-4 may be a new biomarker for predicting the prognosis of hepatocellular carcinoma; meanwhile, targeting lnc-ATG9B-4 might serve as a potential strategy for the treatment hepatocellular carcinoma.
Permissive HLA-DPB1 mismatches in HCT depend on immunopeptidome divergence and editing by HLA-DM
Authors: Meurer Thuja , Crivello Pietro , Metzing Maximilian , Kester Michel , Megger Dominik A. , Chen Weiqiang , van Veelen Peter A. , van Balen Peter , Westendorf Astrid M. , Homa Georg , Layer Sophia E. , Turki Amin T. , Griffioen Marieke , Horn Peter A. , Sitek Barbara , Beelen Dietrich W. , Falkenburg J. H. Frederik , Arrieta-Bolaños Esteban , Fleischhauer Katharina
Published: October 2020

In hematopoietic cell transplantation (HCT), permissive HLA-DPB1 mismatches between patients and their unrelated donors are associated with improved outcomes compared with nonpermissive mismatches, but the underlying mechanism is incompletely understood. Here, we used mass spectrometry, T-cell receptor-β (TCRβ) deep sequencing, and cellular in vitro models of alloreactivity to interrogate the HLA-DP immunopeptidome and its role in alloreactive T-cell responses. We find that permissive HLA-DPB1 mismatches display significantly higher peptide repertoire overlaps compared with their nonpermissive counterparts, resulting in lower frequency and diversity of alloreactive TCRβ clonotypes in healthy individuals and transplanted patients. Permissiveness can be reversed by the absence of the peptide editor HLA-DM or the presence of its antagonist, HLA-DO, through significant broadening of the peptide repertoire. Our data establish the degree of immunopeptidome divergence between donor and recipient as the mechanistic basis for the clinically relevant permissive HLA-DPB1 mismatches in HCT and show that permissiveness is dependent on HLA-DM–mediated peptide editing. Its key role for harnessing T-cell alloreactivity to HLA-DP highlights HLA-DM as a potential novel target for cellular and immunotherapy of leukemia.
Generating realistic null hypothesis of cancer mutational landscapes using SigProfilerSimulator
Authors: Bergstrom Erik N. , Barnes Mark , Martincorena Iñigo , Alexandrov Ludmil B.
Published: October 2020

Background

Performing a statistical test requires a null hypothesis. In cancer genomics, a key challenge is the fast generation of accurate somatic mutational landscapes that can be used as a realistic null hypothesis for making biological discoveries.

Results

Here we present SigProfilerSimulator, a powerful tool that is capable of simulating the mutational landscapes of thousands of cancer genomes at different resolutions within seconds. Applying SigProfilerSimulator to 2144 whole-genome sequenced cancers reveals: (i) that most doublet base substitutions are not due to two adjacent single base substitutions but likely occur as single genomic events; (ii) that an extended sequencing context of ± 2 bp is required to more completely capture the patterns of substitution mutational signatures in human cancer; (iii) information on false-positive discovery rate of commonly used bioinformatics tools for detecting driver genes.

Conclusions

SigProfilerSimulator’s breadth of features allows one to construct a tailored null hypothesis and use it for evaluating the accuracy of other bioinformatics tools or for downstream statistical analysis for biological discoveries. SigProfilerSimulator is freely available at https://github.com/AlexandrovLab/SigProfilerSimulator with an extensive documentation at https://osf.io/usxjz/wiki/home/.
IP4M: an integrated platform for mass spectrometry-based metabolomics data mining
Authors: Liang Dandan , Liu Quan , Zhou Kejun , Jia Wei , Xie Guoxiang , Chen Tianlu
Published: October 2020

Background

Metabolomics data analyses rely on the use of bioinformatics tools. Many integrated multi-functional tools have been developed for untargeted metabolomics data processing and have been widely used. More alternative platforms are expected for both basic and advanced users.

Results

Integrated mass spectrometry-based untargeted metabolomics data mining (IP4M) software was designed and developed. The IP4M, has 62 functions categorized into 8 modules, covering all the steps of metabolomics data mining, including raw data preprocessing (alignment, peak de-convolution, peak picking, and isotope filtering), peak annotation, peak table preprocessing, basic statistical description, classification and biomarker detection, correlation analysis, cluster and sub-cluster analysis, regression analysis, ROC analysis, pathway and enrichment analysis, and sample size and power analysis. Additionally, a KEGG-derived metabolic reaction database was embedded and a series of ratio variables (product/substrate) can be generated with enlarged information on enzyme activity. A new method, GRaMM, for correlation analysis between metabolome and microbiome data was also provided. IP4M provides both a number of parameters for customized and refined analysis (for expert users), as well as 4 simplified workflows with few key parameters (for beginners who are unfamiliar with computational metabolomics). The performance of IP4M was evaluated and compared with existing computational platforms using 2 data sets derived from standards mixture and 2 data sets derived from serum samples, from GC–MS and LC–MS respectively.

Conclusion

IP4M is powerful, modularized, customizable and easy-to-use. It is a good choice for metabolomics data processing and analysis. Free versions for Windows, MAC OS, and Linux systems are provided.
Breeding strategies for animal resilience to weather variation in meat sheep
Authors: Sánchez-Molano Enrique , Kapsona Vanessa V. , Oikonomou Stavroula , McLaren Ann , Lambe Nicola , Conington Joanne , Banos Georgios
Published: October 2020

Background

The alteration in weather patterns expected due to climate change will affect farm animal performance, probably resulting in lower quantity and quality of available products. A potential mitigation strategy would be to breed selected animals for enhanced resilience to climate change. In this context, resilience would reflect stable animal performance in spite of weather variation. The objectives of this study were to (i) derive and characterise novel animal resilience phenotypes, (ii) investigate their genetic profiles and (iii) assess the impact of integrating them in breeding strategies for genetic improvement in meat sheep.

Results

Random regression models were used to jointly analyse live body weight measured in different time points throughout the growth phases of 4469 Scottish Blackface sheep and weather variables during the same period to derive novel resilience phenotypes. The genetic analysis of these phenotypes revealed significant genetic variance and heritability, and an antagonistic genetic correlation with some animal performance traits. Simulated breeding strategies demonstrated that a relative emphasis of 10% on resilience compared to other traits would enhance performance stability against weather volatility without compromising animal growth.

Conclusions

Novel resilience traits exhibited sufficient genetic variation to be amenable to genetic improvement with selective breeding and are recommended to be included in future breeding goals.
Short-duration, submaximal intensity exercise stress combined with adenosine triphosphate decreases artifacts in myocardial perfusion single-photon emission computed tomography
Authors: Shinoda Yukinori , Tachibana Koichi , Minamisaka Tomoko , Fukuoka Hidetada , Inui Hirooki , Ueno Keisuke , Inoue Soki , Mine Kentaro , Ueda Kumpei , Hoshida Shiro
Published: October 2020

Background

Myocardial perfusion single-photon emission computed tomography (SPECT) imaging with stress is a useful examination for detecting coronary artery disease. Since the presence of artifacts is remaining challenges, we aimed to define the minimum intensity of low-grade exercise stress levels combined with drug stress to reduce undesired artifacts and their related factors.

Methods

We divided patients with suspicious coronary artery disease into 4 groups as follows: group A, adenosine triphosphate (ATP) for 6 min; group A + 25 W, ATP + 25 W exercise for 6 min; group A + 35 W, ATP + 35 W exercise for 6 min; group A + 45 W, ATP + 45 W exercise for 6 min) and enrolled only those whose summed stress scores were < 3. Undesired artifacts were evaluated on the basis of heart-to-liver activity (H/L) ratio and heart-to-10 pixels below the heart (H/below the H) ratio.

Results

The logarithmic values of H/L and H/below the H ratios were significantly higher in groups A + 35 W and A + 45 W than in group A (p < 0.05, each). In all the patients, the logarithmic values of H/L and H/below the H ratios positively correlated with the increment of rate pressure product (RPP, p = 0.002 and p = 0.005, respectively) after stress in the univariate analysis. The left ventricular end-diastolic volume (LVEDV) after stress (p = 0.002) negatively correlated with the logarithmic value of H/below the H ratio, but not H/L ratio. Although the increment of RPP was independently associated with the logarithmic values of both H/L (p = 0.001) and H/below the H ratios (p = 0.005), LVEDV was also independently associated with the logarithmic value of H/below the H ratio (p < 0.001) in multivariate regression analysis under adjusting with age and sex.

Conclusion

ATP plus ≥35 W exercise stress for 6 min was useful for reducing undesired artifacts after stress in myocardial perfusion SPECT. LVEDV after stress in addition to the increment of RPP was independently associated with the H/below the H ratio, but not the H/L ratio.
Proficiencies of military medical officers in intubating difficult airways
Authors: Lim Jonathan ZM , Chew Shi Hao , Chin Benjamin ZB , Siew Raymond CH
Published: October 2020

Background

This study sheds light on the proficiency of military medical officers who had received between 2 and 3 years of post-graduate training, in the handling of the difficult airway in a trauma manikin simulator using direct and video laryngoscopes.

Method

One hundred thirty-three doctors from the Singapore Armed Forces Medical Officer Cadet Course were assessed using high-fidelity simulator models with standardised difficult airways (simulator with tongue-swelling and cervical collar). They used the Macintosh direct laryngoscope (DL), King Vision channelled-blade laryngoscope (KVC), King Vision non-channelled blade laryngoscope (KVNC), and the McGrath (MG) laryngoscope on the same model in a randomised sequence. The intubation success rates and time to intubation were recorded and analysed for the study.

Results

The medical officers had a 71.4% intubation success rate with the DL on the difficult airway trauma simulator model and the mean time to intubation of 40.1 s. With the KVC, the success rate is 86.5% with mean intubation time of 40.4 s. The KVNC produced 24.8% success rate, with mean time to intubation of 53.2 s. The MG laryngoscope produced 85.0% success rate, with a mean time of intubation of 37.4 s.

Conclusion

Military medical officers with 2–3 years of post-graduate training had a success rate of 71.4% success rate intubating a simulated difficult airway in a trauma setting using a DL. Success rates were improved with the use of KVC and the MG laryngoscope, but was worse with the KVNC.
Early detection of non-invasive ventilation failure among acute respiratory failure patients in the emergency department
Authors: Liengswangwong W. , Yuksen C. , Thepkong T. , Nakasint P. , Jenpanitpong C.
Published: October 2020

Background

Non-invasive mechanical ventilation (NIV) has become an alternative to an invasive artificial airway for the management of acute respiratory failure (ARF). NIV failure causes delayed intubation, which eventually has been associated with increased morbidity and mortality. This study aimed to develop the clinical scoring system of NIV failure in ARF patients.

Methods

This study was a diagnostic, retrospectively cross-sectional, and exploratory model at the Emergency Medicine Department in Ramathibodi Hospital between February 2017 and December 2017. We included all of the acute respiratory failure patients aged > 18 years and received non-invasive ventilation (NIV). Clinical factors associated with NIV failure were recorded. The predictive model and prediction score for NIV failure were developed by multivariable logistic regression analysis.

Result

A total of 329 acute respiratory failure patients have received NIV success (N = 237) and failure (N = 92). This study showed that NIV failure was associated with heart rate >  110 bpm, systolic BP <  110 mmHg, SpO2 < 90%, arterial pH < 7.30 and serum lactate. The clinical scores were classified into three groups: low, moderate, and high.

Conclusion

We suggested that the novel clinical scoring of the NIV failure in this study may use as a good predictor for NIV failure in the emergency room.
Improving stamina and mobility with preop walking in surgical patients with frailty traits –OASIS IV: randomized clinical trial study protocol
Authors: Hoque Laboni , Dewolf Ryan , Meyers David , White Daniel K. , Mazor Kathleen M. , Stefan Mihaela , Crawford Sybil , Alavi Karim , Yates Jennifer , Maxfield Mark , Lou Feiran , Uy Karl , Walz Matthias , Kapoor Alok
Published: October 2020

Background

Frail older surgical patients face more than a two-fold increase in postoperative complications, including myocardial infarction, deep vein thrombosis, pulmonary embolism, pneumonia, ileus, and others. Many of these complications occur because of postoperative loss of stamina and poor mobility. Preoperative exercise may better prepare these vulnerable patients for surgery. We present the protocol for our ongoing randomized trial to assess the impact of a preoperative walking intervention with remote coaching and pedometer on outcomes of stamina (six-minute walk distance- 6MWD) and mobility (postoperative steps) in older adults with frailty traits.

Methods

We will be conducting a randomized clinical trial with a total of 120 patients permitting up to a 33% rate of attrition, to reach a final sample size of 80 (with 40 patients for each study arm). We will include patients who are age 60 or higher, score 4 or greater on the Edmonton Frailty Scale assessment, and will be undergoing a surgical operation that requires a 2 or more night hospital stay to be eligible for our trial. Using block randomization stratified on baseline 6MWD, we will assign patients to wear a pedometer. At the end of three baseline days, an athletic trainer (AT) will provide a daily step count goal reflecting a 10–20% increase from baseline. Subsequently, the AT will call weekly to further titrate the goal or calls more frequently if the patient is not meeting the prescribed goal. Controls will receive general walking advice. Our main outcome is change in 6MWD on postoperative day (POD) 2/3 vs. baseline. We will also collect 6MWD approximately 4 weeks after surgery and daily in-hospital steps.

Conclusion

If changes in a 6MWD and step counts are significantly higher for the intervention group, we believe this will confirm our hypothesis that the intervention leads to decreased loss of stamina and mobility. Once confirmed, we anticipate expanding to multiple centers to assess the interventional impact on clinical endpoints.

Trial registration

The randomized clinical trial was registered on clinicaltrials.gov under the identifier NCT03892187 on March 27, 2019.
Trends and epidemiological analysis of hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and human T-cell lymphotropic virus among Iranian blood donors: strategies for improving blood safety
Authors: Omidkhoda Azadeh , Razi Bahman , Arabkhazaeli Ali , Amini Kafi-Abad Sedigheh
Published: October 2020

Background

Blood transfusion is associated with potential risks of transfusion-transmitted infections (TTIs). Different strategies are needed to monitor blood safety and screen the donors’ efficacy, such as evaluation of the prevalence and trends of TTIs. This study was conducted to evaluate the prevalence and trends of TTIs, including hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and human T-cell lymphotropic virus (HTLV 1/2), and the impact of the donors’ characteristics such as age, sex, and donor status on the prevalence of TTIs in blood donors in seven large provinces of Iran from 2010 to 2018.

Methods

This study was conducted on the data collected from all blood donations in seven Iranian Blood Transfusion Centers including Ardabil, Alborz, Guilan, West Azarbaijan, North, Razavi, and South Khorasan from April 2010 to March 2018. Demographic characteristics, number of donations, donor status, and screening and confirmatory serological results of all blood donations were collected from Iranian Blood Transfusion Organizations (IBTO) national database. The prevalence and trend of HBV, HCV, HIV, and HTLV 1/2 infections were reported according to the donation year and donor’s characteristics.

Results

The analysis of the prevalence and trend of TTIs in 3,622,860 blood donors showed a significant decreasing trend in first-time and regular donors. Additionally, compared to first- time donors, regular donors made safer blood donations with lower risks of HBV, HIV, HCV and HTLV 1/2 (P < 0.0001). Although the prevalence of HTLV 1/2 and HBV was higher in females, TTIs had a significant decreasing trend in males and females. Finally, it was found that the prevalence of HBV and HTLV 1/2 increased with age up to 40–49 years and then decreased thereafter.

Conclusions

The decreasing trends of TTIs in Iranian donors during 9 years may indicate that the various strategies implemented by IBTO have been effective in recent years. Other factors such as a decrease in the prevalence of specific TTIs in the general population might have also contributed to these declines.
The chronic kidney disease perception scale (CKDPS): development and construct validation
Authors: Anuar Haryati , Shah Shamsul Azhar , Abdul Gafor Abdul Halim , Mahmood Mohd Ihsani
Published: October 2020

Background

Chronic kidney disease has become a major health problem around the world. It displays no symptoms until the later stages. Therefore, its early detection is crucial, and a suitable intervention is necessary to halt its development. The aim of this study was to develop and validate a recently formulated Chronic Kidney Disease Perception Scale (CKDPS) for diabetic patients based on Social Psychology, and their perceptions based on the Health Belief Model (HBM).

Methods

The newly developed CKDPS instrument was tested on 300 patients with diabetes mellitus in a cross-sectional study. The number of domains, model-fit index, construct validity, and internal consistency of this instrument were determined using exploratory (EFA) and confirmatory factor analysis (CFA).

Results

The EFA yielded nine domains: illness identity, timeline motivation, medical practice and co-operation for Social Psychology, and perceived benefit, perceived barriers, perceived susceptibility, perceived severity, and perceived cue to action for HBM. Four items with low factor loading were removed. CFA yielded the following fit indices for Social Psychology: the goodness of fit index (GFI) = 0.889, comparative fit index (CFI) = 0.934, root mean square error of approximation (RMSEA) = 0.053, normed chi-square (NC) = 1.831; and the following for HBM: GFI = 0.834, CFI = 0.957, RMSEA = 0.053, NC = 1.830. Values of Cronbach’s α ranged between 0.760 and 0.909.

Conclusions

The CKDPS includes 61 questions across nine domains, divided under two categories of Social Psychology and HBM. It is also a valid and reliable tool for measuring diabetic patients’ perception of CKD prevention that can be used in larger studies.
Quality assessment of evidence-based clinical practice guidelines for the management of pregnant women with sickle cell disease using the AGREE II instrument: a systematic review
Authors: Amer Yasser S. , Sabr Yasser , ElGohary Ghada M. , Altaki Amer M. , Khojah Osamah T. , El-Malky Ahmed , Alzahrani Musa F.
Published: October 2020

Background

The management of pregnant women with sickle cell disease (SCD) poses a major challenge for maternal healthcare services owing to the potential for complications associated with morbidity and mortality. Trustworthy evidence-based clinical practice guidelines (CPGs) have a major impact on the positive outcomes of appropriate healthcare. The objective of this study was to critically appraise the quality of recent CPGs for SCD in pregnant women.

Methods

Clinical questions were identified and the relevant CPG and bibliographic databases were searched and screened for eligible CPGs. Each CPG was appraised by four independent appraisers using the AGREE II Instrument. Inter-rater analysis was conducted.

Results

Four eligible CPGs were appraised: American College of Obstetricians and Gynecologists (ACOG), National Heart, Lung, and Blood Institute (NHLBI), National Institute of Health and Care Excellence (NICE), and Royal College of Obstetricians and Gynaecologists (RCOG). Among them, the overall assessments of three CPGs (NICE, RCOG, NHLBI) scored greater than 70%; these findings were consistent with the high scores in the six domains of AGREE II, including:[1] scope and purpose,[2] stakeholder involvement,[3] rigor of development,[4] clarity of presentation,[5] applicability, and [6] editorial independence domains. Domain [3] scored (90%, 73%, 71%), domain [5] (90%, 46%, 47%), and domain [6] (71%, 77%, 52%) for NICE, RCOG, and NHLBI, respectively. Overall, the clinical recommendations were not significantly different between the included CPGs.

Conclusions

Three evidence-based CPGs presented superior methodological quality. NICE demonstrated the highest quality followed by RCOG and NHLBI and all three CPGs were recommended for use in practice.
Vogt-Koyanagi-Harada disease: a retrospective and multicentric study of 41 patients
Authors: Diallo K. , Revuz S. , Clavel-Refregiers G. , Sené T. , Titah C. , Gerfaud-Valentin M. , Seve P. , Jaussaud R.
Published: October 2020

Background

East and South East Asian subjects as well as Amerindians and Hispanic subjects are predominantly affected by Vogt-Koyanagi-Harada disease.

In Europe, only few studies have described the clinical features and treatment of this disease, especially in France.

Methods

This retrospective case series was based on data collected from patients with a VKH disease diagnosed from January 2000 to March 2017, provided by three French Tertiary Centers.

Results

Forty-one patients (16 men and 25 women) were diagnosed: average age at diagnosis was 38.7 years. Patients were mainly from Maghreb (58%), but ethnic origins were multiple. Pleiocytosis was observed in 19 cases (63%) and 17 out of 41 patients showed audio vestibular signs (41%), and 11 showed skin signs (27%). Thirty-four were treated with corticosteroids (83%), 11 with an immunosuppressant treatment (27%) and 5 with biological therapy drugs (13%). Relapse was observed in 41% patients, even though final average visual acuity had improved. We did not find any significant clinical difference in the population from Maghreb compared to other populations, but for age and sex trends, since there was a majority of younger women.

Conclusion

We report here the second largest French cohort reported to date to our knowledge. The multiethnicity in our study suggests that VKH disease should be evoked whatever patients’ ethnicity.
The prevalence and causes of visual impairment among children in Kenya – the Kenya eye study
Authors: Muma Shadrack , Obonyo Stephen
Published: October 2020

Background

Visual impairment is the partial or complete loss of vision in which the presenting visual acuity lie between 6/18-no perceptions of light. In Kenya, little attention has been directed towards children vision and causes of visual impairment. Therefore, this study was designed to investigate the prevalence and causes of visual impairment in the children population of Kenya.

Methods

This cross-sectional population-based study included 3400 (1800, 52.9% female) randomly selected children with a mean age of 12 ± 2 years (range 5–16 years). Visual acuity was taken using Snellens chart at 6 m. Anterior and posterior segment was assessed using slit lamp and indirect ophthalmoscope. The World Health Organization definition formed the baseline for calculating the mean prevalence of visual impairment.

Results

Visual acuity measurements were available for 3240 (95.3%) participants. The mean prevalence of visual impairment based on pin-hole value was 1.7 ± 0.3% using World Health Organization definition. The prevalence of visual impairment based on presenting visual acuity value was 2.4 ± 0.7% using the World Health Organization definition. Multivariate analysis demonstrated that the presence of visual impairment on pin-hole increased significantly with increasing age (odds ratio 1.230, P = .021) and uncorrected refractive error (odds ratio 0.834, P = .032) according to World Health Organization definition. Cases of uncorrected refractive error remained the major cause for presenting visual impairment. Causes of visual impairment due to presenting visual acuity were nystagmus (14%), amblyopia (24%) and uncorrected refractive error (62%).

Conclusion

The prevalence of visual impairment in Kenya is associated with age. Uncorrected refractive error remains the major causes of visual impairment.
Understanding the nature of association between anxiety phenotypes and anorexia nervosa: a triangulation approach
Authors: Lloyd E. Caitlin , Sallis Hannah M. , Verplanken Bas , Haase Anne M. , Munafò Marcus R.
Published: October 2020

Background

Evidence from observational studies suggests an association between anxiety disorders and anorexia nervosa (AN), but causal inference is complicated by the potential for confounding in these studies. We triangulate evidence across a longitudinal study and a Mendelian randomization (MR) study, to evaluate whether there is support for anxiety disorder phenotypes exerting a causal effect on AN risk.

Methods

Study One assessed longitudinal associations of childhood worry and anxiety disorders with lifetime AN in the Avon Longitudinal Study of Parents and Children cohort. Study Two used two-sample MR to evaluate: causal effects of worry, and genetic liability to anxiety disorders, on AN risk; causal effects of genetic liability to AN on anxiety outcomes; and the causal influence of worry on anxiety disorder development. The independence of effects of worry, relative to depressed affect, on AN and anxiety disorder outcomes, was explored using multivariable MR. Analyses were completed using summary statistics from recent genome-wide association studies.

Results

Study One did not support an association between worry and subsequent AN, but there was strong evidence for anxiety disorders predicting increased risk of AN. Study Two outcomes supported worry causally increasing AN risk, but did not support a causal effect of anxiety disorders on AN development, or of AN on anxiety disorders/worry. Findings also indicated that worry causally influences anxiety disorder development. Multivariable analysis estimates suggested the influence of worry on both AN and anxiety disorders was independent of depressed affect.

Conclusions

Overall our results provide mixed evidence regarding the causal role of anxiety exposures in AN aetiology. The inconsistency between outcomes of Studies One and Two may be explained by limitations surrounding worry assessment in Study One, confounding of the anxiety disorder and AN association in observational research, and low power in MR analyses probing causal effects of genetic liability to anxiety disorders. The evidence for worry acting as a causal risk factor for anxiety disorders and AN supports targeting worry for prevention of both outcomes. Further research should clarify how a tendency to worry translates into AN risk, and whether anxiety disorder pathology exerts any causal effect on AN.
Psychological distress among Iranian health-care providers exposed to coronavirus disease 2019 (COVID-19): a qualitative study
Authors: Alizadeh Azizeh , Khankeh Hamid Reza , Barati Mohammad , Ahmadi Yazdan , Hadian Arash , Azizi Maryam
Published: October 2020

Background

Novel corona virus, named COVID-19, has spread rapidly to other countries like Italy, Iran and South Korea and affected all people, especially health-care providers. Therefore, due to the rapid spread of the disease in Iran, the aim of the present study was to explore psychological distress experienced by Iranian health-care providers in the first few weeks of the corona virus outbreak.

Methods

The present qualitative study was conducted on 18 Iranian health-care providers exposed to COVID − 19 using a content analysis method. Purposeful sampling was used to select the participants and continued until data saturation was reached. Data were collected using semi-structured interviews and then the qualitative data were analyzed through direct content analysis.

Results

By analyzing 236 primary codes, two main categories were extracted from the experiences of health-care providers during corona virus outbreak. The first category included Occupational demands with three sub-categories: nature of illness, Organizational demands and social demands. The second category was Supportive resources included personal support and social support.

Conclusions

The results of this study found that there were some barriers and challenges to medical personnel exposed to COVID-19 that caused psychological distress. Some of these problems related to the nature of illness, others related to social and organizational demands and some of supportive resources buffer the relationship between occupational demands and psychological distress.
The impact of hearing impairment on early academic achievement in Aboriginal children living in remote Australia: a data linkage study
Authors: Su Jiunn-Yih , Guthridge Steven , He Vincent Yaofeng , Howard Damien , Leach Amanda Jane
Published: October 2020

Background

The prevalence of otitis media (OM) and related hearing loss has remained persistently high among some groups of Australian Aboriginal children who are also reported to have poor academic outcomes. The general literature remains inconclusive about the association between OM-related hearing loss and academic performance in primary school. This study aimed to investigate this association in Aboriginal children living in the Northern Territory (NT) of Australia.

Methods

A retrospective, observational cohort study was conducted for 2208 NT Aboriginal children, aged about 8 years, living in remote and very remote communities. The explanatory variable was audiometrically determined hearing level as recorded in the Remote Hearing Assessment dataset. The outcome variable consisted of scale scores in the five domains of the National Assessment Program – Literacy and Numeracy (NAPLAN) for Year 3. Other linked datasets used in the study included school attendance records, perinatal records and community level information on relative remoteness, socioeconomic disadvantage and housing crowdedness. Fixed effects linear regression models were used for statistical analyses.

Results

Compared with children with normal hearing and after controlling for a range of covariates, children with mild hearing impairment (HI) scored lower in Writing and Spelling by 15.0 points (95% CI: − 22.4 to − 7.6, p < 0.0005) and 5.0 points (95% CI: − 9.6 to − 0.3, p = 0.037), equivalent to 7.3 and 2.1% of the mean score, respectively. Children with moderate or worse HI scored lower in Writing and Numeracy by 13.4 points (95% CI, − 24.8 to − 1.9, p = 0.022) and 15.2 points (95% CI, − 27.6 to − 2.7, p = 0.017), both equivalent to 6.3% of the mean score the respective domain. Other factors associated with poorer NAPLAN results included being male, lower Year 2 school attendance, low birthweight, average household size> 5 persons, living in a very remote community and speaking English as a second language.

Conclusions

OM-related HI was independently associated with poorer early year academic achievement in Aboriginal children living in remote NT communities. Interventions to improve academic outcomes for Aboriginal children must incorporate actions to address the negative impact associated with HI through early detection, effective treatment and ongoing support for affected children.
Differences in Achilles tendon stiffness in people with gout: a pilot study
Authors: Otter Simon , Payne Catherine , Jones Anna-Marie , Webborn Nick , Watt Peter
Published: October 2020

Background

Gout has been associated with weaker foot/leg muscles and altered gait patterns. There is also evidence of on-going foot pain and an increased risk of tendinopathy, with the Achilles and patella tendons most frequently affected in gout. Additionally, the inflammation associated with gout may change tissue elasticity. Ultrasound imaging utilising shear wave elastography (SWE) offers a non-invasive method of quantifying changes in tendon stiffness. SWE findings have not previously been reported in individuals with gout. We sought to determine differences in Achilles tendon stiffness in people with gout compared to controls (non-gout).

Methods

A cross sectional study comparing 24 people with gout and 26 age/sex-matched controls. Clinical and demographic data were collated, and US imaging used to determine tendon thickness, presence of gouty tophi and/or aggregates and levels of angiogenesis. Ten shear wave elastography (SWE) measures were taken along the centre of a longitudinal section of the mid-portion of each Achilles tendon. Prior to data collection, intra-observer error was good (>0.69). Data were summarised using descriptive statistics and a repeated measures ANCOVA was used to compare SWE measures between the two groups for the left and right foot separately after accounting for Body Mass Index (BMI).

Results

A small proportion of those with gout presented with intra-tendon aggregates and/or intra-tendon tophi in one or both tendons. There was no statistically significant difference in tendon thickness between groups. Neo-vascularity was present in a third of gout participants. SWE findings demonstrated significantly reduced tendon stiffness in those with gout compared to controls: right Achilles mdiff =1.04 m/s (95% CI (0.38 to 1.7) p = 0.003 and left Achilles mdiff = 0.7 m/s (95% CI 0.09 to 1.32) p = 0.025. No relationship between the presence of tophi and SWE values were detected.

Conclusion

Subjects with chronic gout show significantly reduced Achilles tendon stiffness compared to non-gout controls. From a clinical standpoint, our findings were similar to SWE measurements in subjects with Achilles tendinopathy and who did not have gout.
The risk factors related to the severity of pain in patients with Chronic Prostatitis/Chronic Pelvic Pain Syndrome
Authors: Chen Jing , Zhang Haomin , Niu Di , Li Hu , Wei Kun , Zhang Li , Yin Shuiping , Liu Longfei , Zhang Xiansheng , Zhang Meng , Liang Chaozhao
Published: October 2020

Background

Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a disease with diverse clinical manifestations, such as pelvic pain or perineal pain. Although recent studies found several risk factors related to the pain severity of CP/CPPS patients, results were inconsistent. Here, we aimed to identify novel risk factors that are closely related to the severity of pain in patients with CP/CPPS.

Methods

We retrospectively collected the clinical records from patients with CP/CPPS from March 2019 to October 2019. The questionnaire was used to obtain related parameters, such as demographics, lifestyle, medical history, etc. To identify potential risk factors related to pain severity, we used the methods of univariate and multivariate logistic regression analyses. Further, to confirm the relationship between these confirmed risk factors and CP/CPPS, we randomly divided CP/CPPS patients into the training and the validation cohorts with a ratio of 7:3. According to the co-efficient result of each risk factor calculated by multivariate logistic regression analysis, a predicting model of pain severity was established. The receiver operating characteristic curve (ROC), discrimination plot, calibration plot, and decision curve analyses (DCA) were used to evaluate the clinical usage of the current model in both the training and validation cohorts.

Results

A total of 272 eligible patients were enrolled. The univariate and multivariate logistic regression analysis found that age [odds ratio (OR): 2.828, 95% confidence intervals (CI): 1.239–6.648, P = 0.004], holding back urine (OR: 2.413, 95% CI: 1.213–4.915, P = 0.005), anxiety or irritability (OR: 3.511, 95% CI: 2.034–6.186, P < 0.001), contraception (OR: 2.136, 95% CI:1.161–3.014, P = 0.029), and smoking status (OR: 1.453, 95% CI: 1.313–5.127, P = 0.013) were the risk factors of pain severity. We then established a nomogram model, to test whether these factors could be used to predict the pain severity of CP/CPPS patients in turn. Finally, ROC, DCA, and calibration analyses proved the significance and stability of this nomogram, further confirmed that these factors were closely related to the pain severity of CP/CPPS patients.

Conclusions

We identify age, holding back urine, anxiety or irritability, contraception, and smoking are risk factors closely related to the pain severity in patients with CP/CPPS. Our results provide novel inspirations for clinicians to design the personalized treatment plan for individual CP/CPPS patient who has suffered different encounters.
Laparoscopic resection of a large clinically silent paraganglioma at the organ of Zuckerkandl: a rare case report and review of the literature
Authors: Ren Xiang , Shang Jiwen , Ren Ruimin , Zhang Huajun , Yao Xue
Published: October 2020

Background

Large paraganglioma of the Zuckerkandl organ (POZ) is extremely rare. The patient can occasionally be paucisymptomatic, further obscuring the diagnosis and carrying high mortality. Recommended treatment for large paraganglioma (PGL) is open surgical removal. We report a case of successful laparoscopic resection of a large POZ with normal blood pressure in a 45-year-old man.

Case presentation

A 45-year-old man was hospitalized because of hyperglycemia. Computed tomography of the abdomen and the serum and urinary catecholamine levels confirmed the diagnosis of large POZ. But his blood pressure was normal and he underwent laparoscopic tumor excision successfully. During 6 months follow-up after laparoscopy, serum and urinary catecholamines were normal but glycaemia remained high level. DNA analysis of the succinate dehydrogenase complex subunits B (SDHB) and SDHD revealed no mutation.

Conclusions

POZ is an unusual mass and preoperative diagnosis can be difficult in clinically silent cases. PGL cannot be excluded in patients with normal blood pressure. Even a large POZ can be excised laparoscopically by following proper techniques.
Adherence to breast cancer guidelines is associated with better survival outcomes: a systematic review and meta-analysis of observational studies in EU countries
Authors: Ricci-Cabello Ignacio , Vásquez-Mejía Adrián , Canelo-Aybar Carlos , Niño de Guzman Ena , Pérez-Bracchiglione Javier , Rabassa Montserrat , Rigau David , Solà Ivan , Song Yang , Neamtiu Luciana , Parmelli Elena , Saz-Parkinson Zuleika , Alonso-Coello Pablo
Published: October 2020

Background

Breast cancer (BC) clinical guidelines offer evidence-based recommendations to improve quality of healthcare for patients with or at risk of BC. Suboptimal adherence to recommendations has the potential to negatively affect population health. However, no study has systematically reviewed the impact of BC guideline adherence -as prognosis factor- on BC healthcare processes and health outcomes. The objectives are to analyse the impact of guideline adherence on health outcomes and on healthcare costs.

Methods

We searched systematic reviews and primary studies in MEDLINE and Embase, conducted in European Union (EU) countries (inception to May 2019). Eligibility assessment, data extraction, and risk of bias assessment were conducted by one author and crosschecked by a second. We used random-effects meta-analyses to examine the impact of guideline adherence on overall survival and disease-free survival, and assessed certainty of evidence using GRADE.

Results

We included 21 primary studies. Most were published during the last decade (90%), followed a retrospective cohort design (86%), focused on treatment guideline adherence (95%), and were at low (80%) or moderate (20%) risk of bias. Nineteen studies (95%) examined the impact of guideline adherence on health outcomes, while two (10%) on healthcare cost. Adherence to guidelines was associated with increased overall survival (HR = 0.67, 95%CI 0.59–0.76) and disease-free survival (HR = 0.35, 95%CI 0.15–0.82), representing 138 more survivors (96 more to 178 more) and 336 patients free of recurrence (73 more to 491 more) for every 1000 women receiving adherent CG treatment compared to those receiving non-adherent treatment at 5 years follow-up (moderate certainty). Adherence to treatment guidelines was associated with higher costs, but adherence to follow-up guidelines was associated with lower costs (low certainty).

Conclusions

Our review of EU studies suggests that there is moderate certainty that adherence to BC guidelines is associated with an improved survival. BC guidelines should be rigorously implemented in the clinical setting.

Trial registration

PROSPERO (CRD42018092884).
Key stakeholder experiences of an integrated healthcare pilot in Australia: a thematic analysis
Authors: Trankle Steven A. , Usherwood Tim , Abbott Penelope , Roberts Mary , Crampton Michael , Girgis Christian M. , Riskallah John , Chang Yashu , Saini Jaspreet , Reath Jennifer
Published: October 2020

Background

In Australia and other developed countries, chronic illness prevalence is increasing, as are costs of healthcare, particularly hospital-based care. Integrating healthcare and supporting illness management in the community can be a means of preventing illness, improving outcomes and reducing unnecessary hospitalisation. Western Sydney has high rates of diabetes, heart and respiratory diseases and the NSW State Ministry of Health funded a range of key strategies through the Western Sydney Integrated Care Program (WSICP) to integrate care across hospital and community settings for patients with these illnesses. Complementing our previously reported analysis related to specific WSICP strategies, this research provided information concerning overall experiences and perspectives of WSICP implementation and integrated care generally.

Methods

We administered 125 in-depth interviews in two rounds over 12 months with 83 participants including patients and their carers, care facilitators, hospital specialists and nurses, allied health professionals, general practitioners and primary care nurses, and program managers. Half of the participants (n = 42) were interviewed twice. We conducted an inductive, thematic analysis on the interview transcripts.

Results

Key themes related to the set-up and operationalising of WSICP; challenges encountered; and the added value of the program. Implementing WSICP was a large and time consuming undertaking but challenges including those with staffing and information technology were being addressed. The WSICP was considered valuable in reducing hospital admissions due to improved patient self-management and a focus on prevention, greater communication and collaboration between healthcare providers across health sectors and an increased capacity to manage chronic illness in the primary care setting.

Conclusions

Patients, carers and health providers experienced the WSICP as an innovative integrated care model and valued its patient-centred approach which was perceived to improve access to care, increase patient self-management and illness prevention, and reduce hospital admissions. Long-term sustainability of the WSICP will depend on retaining key staff, more effectively sharing information including across health sectors to support enhanced collaboration, and expanding the suite of activities into other illness areas and locations. Enhanced support for general practices to manage chronic illness in the community, in collaboration with hospital specialists is critical. Timely evaluation informs ongoing program implementation.