bluuebunny/crossref_metadata_2025 huggingface dataset:
The efficacy of a leukotriene receptor antagonist in the treatment of human rectal aberrant crypt foci: a nonrandomized, open-label, controlled trial
Authors: Higurashi Takuma , Arimoto Jun , Ashikari Keiichi , Takatsu Tomohiro , Misawa Noboru , Yoshihara Tsutomu , Matsuura Tetsuya , Fuyuki Akiko , Ohkubo Hidenori , Nakajima Atsushi
Published: August 2020

Background

Leukotriene receptor antagonists (LTRAs) are broadly used for the management of allergic asthma and have recently been indicated to inhibit carcinogenesis and cancer cell growth. In colorectal cancer (CRC) chemoprevention studies, the occurrence of adenoma or CRC itself is generally set as the trial endpoint. Although the occurrence rate of CRC is the most confident endpoint, it is inappropriate for chemoprevention studies because CRC incidence rate is low in the general population and needed for long-term monitoring. Aberrant crypt foci (ACF), defined as lesions containing crypts that are larger in diameter and darker in methylene blue staining than normal crypts, are regarded to be a fine surrogate biomarker of CRC. Therefore, this prospective study was designed to explore the chemopreventive effect of LTRA on colonic ACF formation and the safety of the medicine in patients scheduled for a poly resection as a pilot trial leading the CRC chemoprevention trial.

Methods

This study is a nonrandomized, open-label, controlled trial in patients with colorectal ACF and polyps scheduled for a polypectomy. Participants meet the inclusion criteria will be recruited, and the number of ACF in the rectum will be counted at the baseline colonoscopic examination. Next, the participants will be assigned to the LTRA or no treatment group. Participants in the LTRA group will continue 10 mg of oral montelukast for 8 weeks, and those in the no treatment group will be observed without the administration of any additional drugs. At the end of the 8-week LTRA intervention period, a polypectomy will be conducted to evaluate the changes in the number of ACF, and cell proliferation in the normal colorectal epithelium will be analyzed.

Discussion

This will be the first study to investigate the effect of LTRAs on colorectal ACF formation in humans.

Trial registration

This trial has been registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry asUMIN000029926. Registered 10 November 2017.
A case report of exudative retinal detachment derived from orbital cellulitis in mainland China
Authors: Song Wei , Du Cheng , Zhang Yongjie
Published: August 2020

Background

Orbital cellulitis is a rare cause of exudative retinal detachment. Hereby, we aimed to report the first case of exudative retinal detachment derived from orbital cellulitis in mainland China.

Case presentation

A 16-year-old girl developed severe left orbital cellulitis in 4 days. Two exudative retinal detachment lesions were presented in her left eye retina. Blood cultures were performed which identified Staphylococcus aureus. However, the cause for the orbital cellulitis was not idenitfied in this patient. Systemic application of antibiotics together with topical antibiotics and corticosteroid was effective to the improvement of orbital cellulitis and resolution of exudative retinal detachment.

Conclusions

The treatment of such clinical condition is that of orbital cellulitis in general. The exudative retinal detachment can resolve to a great extent upon cure of the underlying disease, followed by visual acuity recovery.
Correction to: Thickness profiles of the corneal epithelium along the steep and flat meridians of astigmatic corneas after orthokeratology
Authors: Zhou Jiaqi , Xue Feng , Zhou Xingtao , Naidu Rajeev Krishnan , Qian Yishan
Published: August 2020

An amendment to this paper has been published and can be accessed via the original article.
Schizophrenia patients with a metabolically abnormal obese phenotype have milder negative symptoms
Authors: Wang Juan , Zhang Yulong , Liu Zhiwei , Yang Yating , Zhong Yi , Ning Xiaoshuai , Zhang Yelei , Zhao Tongtong , Xia Lei , Geng Feng , Tao Rui , Fan Mei , Ren Zhenhua , Liu Huanzhong
Published: August 2020

Background

Schizophrenia patients with a metabolically abnormal obese (MAO) phenotype have been shown poor cardiovascular outcomes, but the characteristics of their current psychiatric symptoms have not been characterized. This study mainly explored the psychiatric symptoms of schizophrenia patients with the MAO phenotype.

Methods

A total of 329 patients with schizophrenia and 175 sex- and age-matched people without schizophrenia from Anhui Province in China were enrolled. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate the mental symptoms of the schizophrenia patients. The MAO phenotype was defined as meeting 1–4 metabolic syndrome criteria (excluding waist circumference) and having a body mass index (BMI) ≥ 28 kg/m2. And, metabolically healthy normal-weight (MHNW) phenotype was defined as meeting 0 criteria for metabolic syndrome and 18.5 ≤ BMI < 24 kg/m2.

Results

Overall, 15.8% of the schizophrenia patients and 9.1% of the control group were consistent with the MAO phenotype, and the prevalence of MAO in the schizophrenia group was higher than that in the control group. Among the patients with schizophrenia, the MAO group had lower negative factor, cognitive factor and total PANSS scores than the MHNW group. However, when confounding factors were controlled, only the negative factor remained lower significantly.

Conclusion

We found that schizophrenia patients with the MAO phenotype had reduced negative symptoms, which may indicate an internal mechanism linking metabolic disorders and negative symptoms.

Trial registration

This study was registered in the China Clinical Trial Registration Center (No. chiCTR 1,800,017,044).
Barriers in access to healthcare services for individuals with disorders of sex differentiation in Bangladesh: an analysis of regional representative cross-sectional data
Authors: Khan Alam , Fahad T. M. , Manik Md Imran Nur , Ali Hazrat , Ashiquazzaman Md. , Mollah Md Ibrahim , Zaman Tanjeena , Islam Md Shariful , Rahman Moizur , Rahman Aminur , Rahman Mostafizur , Naz Tarannum , Pavel Mahmud Arif , Khan Md. Nuruzzaman
Published: August 2020

Background

Worldwide people in disorder of sex development (DSD) faces multiple barriers while seeking their social rights, particularly healthcare services. We aimed to explore the healthcare opportunities available to them, using patterns of healthcare utilization and difficulties faced by DSD population in accessing healthcare services in Bangladesh.

Methods

Data from a total of 945 DSD population and 71 medical staff were analyzed, collected from three major divisions (Dhaka, Chittagong, and Rajshahi) in Bangladesh during the period of January to December of 2017. A structured questionnaire was used to collect data via face-to-face interviews. Descriptive statistic was used to determine the frequencies of the visit by the DSD population in healthcare facilities as well as to analyze difficulties experienced by the DSD population in getting healthcare services. Multivariate regression analysis was used to explore the association between perceived barriers in getting healthcare services and failures of the DSD population to receive the healthcare services.

Results

Present data revealed that around 80% of DSD population sought healthcare services from government healthcare facilities, where the overall success rate in getting healthcare services was less than 50%. The DSD population reported a number of reasons for failures in getting healthcare services, including non-friendly interaction by non-clinical hospital’s staff, non-friendly interaction by physicians, public fright as general people do not want to mingle with a DSD person, undesirable excess public interest in DSD individuals, and limitation of the treatment opportunities of hospitals to merely male or female patients. Among the stated reasons, the most frequently reported reason was non-friendly interaction by physicians (50.27%), followed by undesirable excess public interest in DSD individuals (50.16%).

Conclusion

DSD population in Bangladesh have limited access to healthcare facilities and facing multiple barriers to get healthcare services. Initiatives from the government and social organizations are important to ensure their access to healthcare services.
Trends of the leprosy control indicators in Benin from 2006 to 2018
Authors: Gnimavo Ronald Sètondji , Djossou Parfait , Sopoh Ghislain Emmanuel , Anagonou Gimatal Esaï , Barogui Yves Thierry , Wadagni Akpéédjé Anita Carolle , Houezo Jean-Gabin , Johnson Roch Christian
Published: August 2020

Background

Leprosy, or Hansen’s disease, is a chronic infectious disease caused by Mycobacterium leprae. The purpose of this study was to describe the epidemiological characteristics of leprosy in Benin from 2006 to 2018.

Methods

This descriptive retrospective study included data from January 2006 to December 2018. The data of all patients treated in the leprosy treatment centres (LTCs) of the Republic of Benin were obtained from the LTC registers and analysed using Stata/SE 11.0 software. Quantum GIS (Geographic Information System) version 2.18.23 software was used for mapping. The main indicators of leprosy were calculated according to the World Health Organization (WHO) recommendations.

Results

During the study period, a total of 2785 (annual average of 214) new cases of leprosy were diagnosed. The median age of the patients was 38 years, with extremes ranging from 6 to 88 years. The sex ratio (males/females) was 1.18 (1509/1276). The departments of Plateau, Atacora, and Zou were the most endemic; their leprosy detection rate per 100,000 population during these thirteen years were 6.46 (479/7414297), 5.38 (534/9932880) and 5.19 (526/10134877), respectively. The leprosy detection rate declined from 3.8 to 1.32 per 100,000 inhabitants. The proportion of paediatric cases varied from 8.56 to 2.67% as the proportion of multibacillary forms increased from 72.95 to 90%. From 2006 to 2018, 622 leprosy patients detected had grade 2 disability (G2D) at screening, indicating an average rate of 5.06 (622/122877474) cases with G2D per million population. The proportion of grade 2 disabilities increased from 21.23 to 32% during the study period. The majority of new leprosy cases among foreign-born persons were Nigerian (85.71%). The completion of multidrug therapy (MDT) for paucibacillary (PB) and multibacillary (MB) leprosy cases ranged from 96.36 to 95.65% and from 90.53 to 94.12%, respectively.

Conclusion

In Benin, leprosy remains a major health challenge; it is important to revitalize the epidemiological surveillance system to achieve its elimination by 2030.
Prevalence of non-communicable diseases and its risk factors among Ijegun-Isheri Osun residents in Lagos State, Nigeria: a community based cross-sectional study
Authors: Idris Israel Oluwaseyidayo , Oguntade Ayodipupo Sikiru , Mensah Ekow Adom , Kitamura Noriko
Published: August 2020

Background

The rapid epidemiologic transition of diseases has adverse implications for low-and middle-income countries (LMICs) like Nigeria due to their limited healthcare, weaker health systems and the westernization of lifestyle. There is a need to evaluate the enormity or otherwise of non-communicable diseases (NCDs) burden in such low resource settings. We performed this survey to determine the prevalence of NCDs and its risk factors among the Ijegun- Isheri Osun community residents of Lagos, Nigeria.

Methods

A community-based cross-sectional survey was performed on 215 respondents recruited consecutively during a population preventive health campaign. Prevalence of three NCDs (hypertension, diabetes and dyslipidaemia) were calculated. Associations between each of these NCDs and selected risk factors were determined using chi square test. Multivariable logistic regression was used to estimate the risk factors of each of the three NCDs.

Results

The prevalence of hypertension was 35.3% (95% CI 29.0–42.1), diabetes 4.6% (95% CI 2.2–8.4) and dyslipidaemia 47.1% (95% CI 41.1–54.8). Among the NCD risk factors, the prevalence of smoking was 41.3% (95% CI 34.2–48.6), alcohol consumption 72.5% (95% CI 65.5–78.7), and physical activity 52.9 (95% CI 45.5–60.2). The independent significant predictors of hypertension were age ≥ 60 years (aOR 4.56; 95% CI: 1.72–12.09) and dyslipidaemia (aOR 5.01; 95% CI: 2.26–11.13). Age ≥ 60 years (aOR 8.83; 95% CI: 1.88–41.55) was an independent predictor of diabetes. Age ≥ 60 years (aOR 29.32; 95% CI: 4.78–179.84), being employed (aOR 11.12; 95% CI: 3.10–39.92), smoking (aOR 2.34; 95% CI: 1.03–5.33) and physical activity (aOR 0.34; 95% CI: 0.15–0.76) were independent predictors of having dyslipidaemia.

Conclusions

The prevalence of hypertension, diabetes and dyslipidaemia and their associated risk factors are high among the respondents of Ijegun-Isheri Osun community of Lagos state, Nigeria. This highlights the need for further implementation research and policy directions to tackle NCD burden in urban communities in Nigeria. These strategies must be community specific, prioritizing the various risk factors and addressing them accordingly.
Social comorbidities? A qualitative study mapping syndemic theory onto gender-based violence and co-occurring social phenomena among Brazilian women
Authors: Xavier Hall Casey D. , Evans Dabney P.
Published: August 2020

Background

Gender-based violence is a globally recognized social problem impacting women and girls worldwide. Intimate partner violence (IPV) represents the most common form of gender-based violence. Among the countries grappling with gender-based violence is Brazil, which has identified high rates of IPV along with co-occurring social conditions such as adverse childhood experiences, community violence, and substance use. While the syndemic framework has incorporated IPV into understandings of HIV and other diseases, none have explicitly applied syndemic framework to understand IPV and co-occurring social conditions -- referred to here as “social comorbidities” -- in the absence of a biological outcome. This study aims to: (1) Examine perspectives on violence and relevant social comorbidities (substance use, community violence, and childhood abuse) among women living in Santo André, São Paulo State, Brazil; and (2) Apply the syndemic framework to a set of social comorbidities among women living in Santo André, São Paulo State, Brazil.

Methods

This thematic analysis applies a syndemic framework to 28 in-depth interviews with women in Santo André, Brazil. Interviews were recorded and transcribed verbatim in Portuguese. Our analysis examined themes relating to IPV, community violence, substance use, and other individual experiences and community issues using syndemics as an organizing framework (e.g. diseases, adverse interactions, disparity conditions, and enhanced disease transmission).

Results

Most participants described experiencing multiple social comorbidities including IPV, adverse childhood experiences, community violence, family violence, and substance use. Adverse interactions included increased financial conflicts, a sense of isolation, and increased severity of violence due to substance use. Long term enhanced “disease” progression included injury, increased mental health symptoms, femicide, and death.

Conclusions

Our results suggest that using a syndemic framework to understand IPV in the context of social comorbidities could be useful for understanding how these social phenomena may mutually reinforce each other and cause adverse interactions. Similar applications across other social phenomena may also be possible.
“Public health is global”: examining Indian stakeholders’ perspectives on Global Health education
Authors: Sawleshwarkar Shailendra , Zodpey Sanjay , Negin Joel
Published: August 2020

Background

Global health education has attracted significant attention in recent years from academic institutions in developed countries. In India however, a recent analysis found that delivery of global health education is fragmented and called for academic institutions to work towards closing the developing country/developed country dichotomy. Our study explored the understanding of global health in the Indian setting and opportunities for development of a global health education framework in Indian public health institutions.

Methods

The study involved semi-structured interviews with staff of Indian public health institutes and other key stakeholders in global health in India. The interview questions covered participants’ interpretation of global health and their opinion about global health education in India. Thematic analysis was conducted. A theoretical framework developed by Smith and Shiffman to explain political priority for global health initiatives was adapted to guide our analysis to explore development of global health education in Indian public health institutions.

Results

A total of 17 semi-structured interviews were completed which involved 12 faculty members from five public health institutes and five stakeholders from national and multilateral organisations. Global health was viewed as the application of public health in real-world setting and at a broader, deeper and transnational scale. The understanding of global health was informed by participants’ exposure to work experiences and interaction with overseas faculty. Most common view about the relationship between global health and public health was that public health has become more global and both are interconnected. Integration of global health education into public health curriculum was supported but there were concerns given public health was still a new discipline in India. Most participants felt that global health competencies are complementary to public health competencies and build on core public health skills. Employability, faculty exposure to global health and ‘sensitisation’ of all stakeholders were key barriers to offering global health education programs.

Conclusion

Global health as a concept and educational practice is embryonic in India but there is considerable potential to grow in order to ensure that education meets the needs of future practitioners of global health in the context of sustainable development.
The effect of distance between holes on the structural stability of subchondral bone in microfracture surgery: a finite element model study
Authors: Yin Xiang Yun , Park Do Young , Kim Young Jick , Ahn Hye Jung , Yoo Seung-Hyun , Min Byoung-Hyun
Published: August 2020

Background

Microfracture is a surgical technique that involves creating multiple holes of 3–4 mm depth in the subchondral bone to recruit stem cells in the bone marrow to the lesion, inducing fibrocartilage repair and knee cartilage regeneration. Recently, it has been reported that increasing the exposed area of the lower cartilaginous bone (drilling a lot of holes) increases the outflow of stem cells, which is expected to affect the physical properties of the subchondral bone when the exposed area is large. The purpose of this study was to analyse the effect of the distance between the holes in the microfracture procedure on the structural stability of the osteochondral bone using a finite element method.

Methods

In this study, lateral aspects of the femoral knee, which were removed during total knee arthroplasty were photographed using microtomography. The model was implemented using a solitary walks program, which is a three-dimensional simplified geometric representation based on the basic microtomography data. A microfracture model was created by drilling 4 mm-deep holes at 1, 1.5, 2, 2.5, 3, 4, and 5 mm intervals in a simplified three-dimensional (3D) geometric femoral model. The structural stability of these models was analysed with the ABAQUS program. We compared the finite element model (FEM) based on the microtomography image and the simplified geometric finite element model.

Results

Von Mises stress of the subchondral bone plate barely increased, even when the distance between holes was set to 1 mm. Altering the distance between the holes had little impact on the structural stability of the subchondral bone plate. Safety factors were all below 1.

Conclusions

Although we did not confirm an optimal distance between holes, this study does provide reference data and an epidemiological basis for determining the optimal distance between the holes used in the microfracture procedure.
Accuracy on the preoperative assessment of patients with adolescent idiopathic scoliosis using biplanar low-dose stereoradiography: a comparison with computed tomography
Authors: Yeung Kwong Hang , Man Gene Chi Wai , Lam Tsz Ping , Ng Bobby Kin Wah , Cheng Jack Chun Yiu , Chu Winnie Chiu Wing
Published: August 2020

Background

Although computed tomography (CT) is commonly used to diagnose the scoliotic spine in patients with adolescent idiopathic scoliosis (AIS) preoperatively, it is limited by the high radiation and prone scanning position. Recently, a new biplanar stereoradiography (EOS) was used to image the scoliotic spine in an upright posture with significantly less radiation in non-severe AIS subjects. However, its reliability to assess preoperative AIS patients remains unreported. Hence, the purpose of this study is to compare the scoliotic curvature between prone (CT) and upright positions (EOS) in preoperative AIS patients.

Methods

Thirty-three pre-operative AIS patients (mean age:18.4 ± 4.2) were recruited. EOS was used to scan the whole thoracic spine at upright position. Whereas on the same day, a conventional CT scan was used to evaluate the spine in prone position. The three-dimensional reconstruction of EOS and CT of the spine were then generated. Using previous validated techniques, multiple scoliotic parameters in both modalities were determined. The agreement between the two modalities was compared using the Bland-Altman test, whereas the correlation was assessed by the intraclass correlation coefficient (ICC).

Results

The mean ICC (prone and upright) of intra-rater/inter-rater reliabilities for the measured parameters were 0.985,0.961/0.969,0.903, respectively. Thoracic Cobb angles, intervertebral wedging and lumbar lordosis correlated significantly between upright EOS imaging radiographs (62.9 ± 9.3°,6.4 ± 2.9° and 48.8 ± 12.4°) and prone CT (47.3 ± 10.0°,5.8 ± 2.7° and 27.9 ± 11.4°; P < 0.001). The apical vertebral wedging and apical intervertebral disc wedging showed a good correlation among the two modalities (upright, 6.5 ± 3.5° and 6.4 ± 2.9°; prone, 6.5 ± 3.6° and 5.8 ± 2.7°; R2 ≥ 0.94; P < 0.01). Similarly, there was significant correlation in apical intervertebral rotation (R2 = 0.834; P < 0.01) between the prone CT (3.4 ± 3.0°) and upright EOS (3.8 ± 3.2°). In addition, the Cobb angle was significantly larger in upright EOS (62.9 ± 9.3°) than in prone CT (47.3 ± 10.0°, P < 0.01) position. There was significant underestimation on scoliotic severity in the prone position when compared with upright position.

Conclusions

Importantly, the image acquisition and reconstruction from EOS can better provide accurate three-dimensional spinal representations of the scoliotic curvature in preoperative AIS patients. Moreover, our findings suggested that scoliotic curvatures in preoperative AIS patients can be largely represented by both imaging modalities despite the difference in body positioning.
Efficient generation of GGTA1-deficient pigs by electroporation of the CRISPR/Cas9 system into in vitro-fertilized zygotes
Authors: Tanihara Fuminori , Hirata Maki , Nguyen Nhien Thi , Sawamoto Osamu , Kikuchi Takeshi , Doi Masako , Otoi Takeshige
Published: August 2020

Background

Xenoantigens are a major source of concern with regard to the success of interspecific xenografts.GGTA1encodes α1,3-galactosyltransferase, which is essential for the biosynthesis of galactosyl-alpha 1,3-galactose, the major xenoantigen causing hyperacute rejection.GGTA1-modified pigs, therefore, are promising donors for pig-to-human xenotransplantation. In this study, we developed a method for the introduction of the CRISPR/Cas9 system into in vitro-fertilized porcine zygotes via electroporation to generateGGTA1-modified pigs.

Results

We designed five guide RNAs (gRNAs) targeting distinct sites inGGTA1.After the introduction of the Cas9 protein with each gRNA via electroporation, the gene editing efficiency in blastocysts developed from zygotes was evaluated. The gRNA with the highest gene editing efficiency was used to generateGGTA1-edited pigs. Six piglets were delivered from two recipient gilts after the transfer of electroporated zygotes with the Cas9/gRNA complex. Deep sequencing analysis revealed that five out of six piglets carried a biallelic mutation in the targeted region ofGGTA1,with no off-target events. Furthermore, staining with isolectin B4 confirmed deficientGGTA1function inGGTA1biallelic mutant piglets.

Conclusions

We establishedGGTA1-modified pigs with high efficiency by introducing a CRISPR/Cas9 system into zygotes via electroporation. Multiple gene modifications, including knock-ins of human genes, in porcine zygotes via electroporation may further improve the application of the technique in pig-to-human xenotransplantation.
A rare case of fulminant type 1 diabetes mellitus accompanied by both acute pancreatitis and myocarditis - case report
Authors: Egashira Fujiko , Kawashima Midori , Morikawa Ai , Kosuda Minami , Ishihara Hisamitsu , Watanabe Kentaro
Published: August 2020

Background

Fulminant type 1 diabetes mellitus (FT1D) is a newly established subtype of type 1 diabetes. Its etiology has not been fully elucidated. Several cases with FT1D have exhibited pancreatitis or myocarditis.

Case presentation

We report a 31-year-old Japanese woman who showed upper abdominal pain and was admitted to a local hospital. She was initially diagnosed with acute pancreatitis based on serum amylase elevation and swelling of the pancreas on computed tomography. Four days after admission, she developed diabetic ketoacidosis and was transferred to our hospital. Her symptoms and laboratory findings met the FT1D criteria. On the 3rd hospital day, electrocardiography (ECG) showed ST-segment elevation, and serum cardiac enzymes were markedly elevated. Because she exhibited late gadolinium enhancement in the apical wall on contrast-enhanced cardiac magnetic resonance imaging, she was diagnosed as acute myocarditis. Abnormal ECG findings and elevations of biomarkers associated with myocarditis showed improvement on the next day.

Conclusions

This is the first case of FT1D accompanied by both pancreatitis and myocarditis and suggests that the pathophysiology of FT1D is related to the common etiology of acute pancreatitis and myocarditis.
Developing and testing a nurse-led intervention to support bereavement in relatives in the intensive care (BRIC study): a protocol of a pre-post intervention study
Authors: van Mol Margo M. C. , Wagener Sebastian , Latour Jos M. , Boelen Paul A. , Spronk Peter E. , den Uil Corstiaan A. , Rietjens Judith A. C.
Published: August 2020

Background

When a patient is approaching death in the intensive care unit (ICU), patients’ relatives must make a rapid transition from focusing on their beloved one’s recovery to preparation for their unavoidable death. Bereaved relatives may develop complicated grief as a consequence of this burdensome situation; however, little is known about appropriate options in quality care supporting bereaved relatives and the prevalence and predictors of complicated grief in bereaved relatives of deceased ICU patients in the Netherlands. The aim of this study is to develop and implement a multicomponent bereavement support intervention for relatives of deceased ICU patients and to evaluate the effectiveness of this intervention on complicated grief, anxiety, depression and posttraumatic stress in bereaved relatives.

Methods

The study will use a cross-sectional pre-post design in a 38-bed ICU in a university hospital in the Netherlands. Cohort 1 includes all reported first and second contact persons of patients who died in the ICU in 2018, which will serve as a pre-intervention baseline measurement. Based on existing policies, facilities and evidence-based practices, a nurse-led intervention will be developed and implemented during the study period. This intervention is expected to use 1) communication strategies, 2) materials to make a keepsake, and 3) a nurse-led follow-up service. Cohort 2, including all bereaved relatives in the ICU from October 2019 until March 2020, will serve as a post-intervention follow-up measurement. Both cohorts will be performed in study samples of 200 relatives per group, all participants will be invited to complete questionnaires measuring complicated grief, anxiety, depression and posttraumatic stress. Differences between the baseline and follow-up measurements will be calculated and adjusted using regression analyses. Exploratory subgroup analyses (e.g., gender, ethnicity, risk profiles, relationship with patient, length of stay) and exploratory dose response analyses will be conducted.

Discussion

The newly developed intervention has the potential to improve the bereavement process of the relatives of deceased ICU patients. Therefore, symptoms of grief and mental health problems such as depression, anxiety and posttraumatic stress, might decrease.

Trial registration

Netherlands Trial Register Registered on 27/07/2019 as NL 7875, www.trialregister.nl
Simulation via instant messaging-Birmingham advance (SIMBA) model helped improve clinicians’ confidence to manage cases in diabetes and endocrinology
Authors: Melson Eka , Davitadze Meri , Aftab Manal , Ng Cai Ying , Ooi Emma , Blaggan Parisha , Chen Wentin , Hanania Thia , Thomas Lucretia , Zhou Dengyi , Chandan Joht Singh , Senthil Latha , Arlt Wiebke , Sankar Sailesh , Ayuk John , Karamat Muhammad Ali , Kempegowda Punith
Published: August 2020

Background

Simulation-based learning (SBL) has been increasingly used in both undergraduate and postgraduate medical training curricula. The aim of Simulation via Instant Messaging-Birmingham Advance (SIMBA) is to create a simple virtual learning environment to improve trainees’ self-reported confidence in diabetes and Endocrinology.

Methods

This study was done as part of the continuous professional development for Health Education England West Midlands speciality trainees in diabetes and Endocrinology. Standardized transcripts of anonymized real-life endocrinology (endocrine session) and diabetes cases (diabetes session) were used in the simulation model. Trainees interacted with moderators through WhatsApp® in this model. All cases were then discussed in detail by a consultant endocrinologist with reference to local, national and international guidelines. Trainee acceptance rate and improvement in their self-reported confidence levels post-simulation were assessed.

Results

70.8% (n = 17/24) and 75% (n = 18/24) strongly agreed the simulation session accommodated their personal learning style and the session was engaging. 66.7% (n = 16/24) strongly felt that the simulation was worth their time. In the endocrine session, there was a significant improvement in trainees’ confidence in the management of craniopharyngioma (p = 0.0179) and acromegaly (p = 0.0025). There was a trend towards improved confidence levels to manage Cushing’s disease and macroprolactinoma. In diabetes session, there was a significant improvement in trainees’ confidence to interpret continuous glucose monitor readings (p = 0.01). There was a trend towards improvement for managing monogenic diabetes, hypoglycaemic unawareness and interpreting Libre readings. Overall, there was a significant improvement in trainees’ confidence in managing cases that were discussed post-simulation.

Conclusion

SIMBA is an effective learning model to improve trainees’ confidence to manage various diabetes and endocrine case scenarios. More sessions with a variety of other speciality case scenarios are needed to further assess SIMBA’s effectiveness and application in other areas of medical training.
The relationship between job satisfaction and turnover intention among nurses in Axum comprehensive and specialized hospital Tigray, Ethiopia
Authors: Gebregziabher Dawit , Berhanie Eskedar , Berihu Hagos , Belstie Addis , Teklay Girmay
Published: August 2020

Background

Nurses’ turnover is a global concern which if not handled well can harm the productivity of an organization. The high turnover rate of health workers critically affects the health system, particularly in countries with limited resources. Hence, effective retention strategies require clear identification of the variables at the workplace that determines nurses’ decision in staying in or leaving their employer organization. The aim of this study is to assess the relationship between job satisfaction and turnover intention among nurses in Axum Comprehensive and Specialized Hospital Tigray, Ethiopia.

Methods

The research was conducted using institution based cross-sectional study design. A total of 148 nurses were included in the study using a systematic random sampling technique. The study was conducted from January 2018 to June, 2019. Data were collected using semi-structured self-administered questionnaires. It was entered into Epidemiological information version 7 and then analyzed using Statistical Package for Social Sciences version 22. Bivariate logistic regression analysis was employed to examine the statistical association between the outcome variable and selected independent variables. All variables with P value < 0.05 in the bivariate analysis were included in the multivariable analysis.

Result

Out of 148 nurses, more than half (64.9%) had the intention to leave the organization. The finding of this study showed that the level of job satisfaction was significantly associated with the overall intention. Nurses who were unsatisfied on their job autonomy were 2.55 (95% CI: 1.194, 5.466) more likely to intend to leave their workplace than nurses who reported to be satisfied. Nurses who were unsatisfied on training opportunity were also 2.55 (95% CI: 1.167, 5.571) times more likely to leave their job than nurses who reported to be satisfied.

Conclusion

The overall turnover intention of nurses was found to be high and significantly associated with dissatisfaction on autonomy, and training opportunity. Therefore, continuous effort should be made by ward managers to enhance nurses’ satisfaction onjob autonomy, and training opportunity.
Absences from work among healthcare workers: are they related to influenza shot adherence?
Authors: Antinolfi Francesca , Battistella Claudio , Brunelli Laura , Malacarne Francesca , Bucci Francesco Giuseppe , Celotto Daniele , Cocconi Roberto , Brusaferro Silvio
Published: August 2020

Background

The coverage for influenza vaccination among healthcare workers (HCWs) is inadequate in many countries despite strong recommendations; is there evidence that influenza vaccination is effective in preventing absenteeism? Aim of the study is to evaluate the influenza vaccination coverage and its effects on absences from work among HCWs of an Italian academic healthcare trust during the 2017–2018 influenza season.

Methods

We performed a retrospective study to identify predictive characteristics for vaccination, and a retrospective cohort study to establish the effect of vaccination on absences among the vaccinated and non-vaccinated cohorts between December 2017 and May 2018. Overall absence rates over the whole observation period and sub-rates over 14-days intervals were calculated; then comparison between the two groups were conducted applying Chi-square test.

Results

Influenza vaccination coverage among 4419 HCWs was 14.5%. Age, university degree, medical care area and physician profile were positively associated with vaccine uptake. Globally during influenza season non-vaccinated HCWs lost 2.47/100 person-days of work compared to 1.92/100 person-days of work among vaccinated HCWs (p < 0.001); significant differences in absences rates resulted when focusing on the influenza epidemic peak.

Conclusions

Factors predicting influenza uptake among HCWs were male sex, working within medical care area and being a physician. Absenteeism among HCWs resulted to be negatively correlated with vaccination against influenza. These findings add evidence to the urgent need to implement better influenza vaccination strategies towards HCWs to tackle vaccine hesitancy among professionals.
A realist evaluation approach to explaining the role of context in the impact of a complex eHealth intervention for improving prevention of cardiovascular disease
Authors: Coorey Genevieve , Peiris David , Neubeck Lis , Redfern Julie
Published: August 2020

Background

Reduction of cardiovascular disease (CVD) is a worldwide health priority and innovative uses of technology-based interventions may assist patients with improving prevention behaviours. Targeting these interventions to recipients most likely to benefit requires understanding how contexts of use influence responsiveness to the intervention, and how this interaction favours or discourages health behaviour. Using a realist evaluation approach, the aim of this study was to examine the contextual factors influencing behaviour change within a multi-feature eHealth intervention with personalised data integration from the primary care electronic health record (EHR).

Methods

Realist evaluation of qualitative data from the Consumer Navigation of Electronic Cardiovascular Tools (CONNECT) randomised trial (N = 934). Thirty-six participants from the intervention group (N = 486) who had completed 12 months of study follow-up were interviewed. Coding of transcripts was structured around configurations of contexts, mechanisms, and outcomes of intervention use. Contextual narratives were derived from thematic analysis of the interviews.

Results

Mechanisms favouring positive health behaviour occurred when participants responded to four interactive features of the intervention. Facilitating mechanisms included greater cognitive engagement whereby participants perceived value and benefit, and felt motivated, confident and incentivised. Participants moved from being unconcerned (or unaware) to more task-oriented engagement with personal CVD risk profile and prevention. Increased personalisation occurred when modifiable CVD risk factors became relatable to lifestyle behaviour; and experiences of feeling greater agency/self-efficacy emerged. Use and non-use of the intervention were influenced by four overarching narratives within the individual’s micro-level and meso-level environments: illness experiences; receptiveness to risk and prevention information; history of the doctor-patient relationship; and relationship with technology.

Conclusions

Intervention-context interactions are central to understanding how change mechanisms activate within complex interventions to exert their impact on recipients. Intervention use and non-use were context-dependent, underscoring the need for further research to target eHealth innovations to those most likely to benefit.
Association of Bacteroides acidifaciens relative abundance with high-fibre diet-associated radiosensitisation
Authors: Then Chee Kin , Paillas Salome , Wang Xuedan , Hampson Alix , Kiltie Anne E.
Published: August 2020

Background

Patients with pelvic malignancies often receive radiosensitising chemotherapy with radiotherapy to improve survival; however, this is at the expense of increased normal tissue toxicity, particularly in elderly patients. Here, we explore if an alternative, low-cost, and non-toxic approach can achieve radiosensitisation in mice transplanted with human bladder cancer cells. Other investigators have shown slower growth of transplanted tumours in mice fed high-fibre diets. We hypothesised that mice fed a high-fibre diet would have improved tumour control following ionising radiation (IR) and that this would be mediated through the gut microbiota.

Results

We investigated the effects of four different diets (low-fibre, soluble high-fibre, insoluble high-fibre, and mixed soluble/insoluble high-fibre diets) on tumour growth in immunodeficient mice implanted with human bladder cancer flank xenografts and treated with ionising radiation, simultaneously investigating the composition of their gut microbiomes by 16S rRNA sequencing. A significantly higher relative abundance ofBacteroides acidifacienswas seen in the gut (faecal) microbiome of the soluble high-fibre group, and the soluble high-fibre diet resulted in delayed tumour growth after irradiation compared to the other groups. Within the soluble high-fibre group, responders to irradiation had significantly higher abundance ofB. acidifaciensthan non-responders. When all mice fed with different diets were pooled, an association was found between the survival time of mice and relative abundance ofB. acidifaciens. The gut microbiome in responders was predicted to be enriched for carbohydrate metabolism pathways, and in vitro experiments on the transplanted human bladder cancer cell line suggested a role for microbial-generated short-chain fatty acids and/or other metabolites in the enhanced radiosensitivity of the tumour cells.

Conclusions

Soluble high-fibre diets sensitised tumour xenografts to irradiation, and this phenotype was associated with modification of the microbiome and positively correlated withB. acidifaciensabundance. Our findings might be exploitable for improving radiotherapy response in human patients.
Deciphering serous ovarian carcinoma histopathology and platinum response by convolutional neural networks
Authors: Yu Kun-Hsing , Hu Vincent , Wang Feiran , Matulonis Ursula A. , Mutter George L. , Golden Jeffrey A. , Kohane Isaac S.
Published: August 2020

Background

Ovarian cancer causes 151,900 deaths per year worldwide. Treatment and prognosis are primarily determined by the histopathologic interpretation in combination with molecular diagnosis. However, the relationship between histopathology patterns and molecular alterations is not fully understood, and it is difficult to predict patients’ chemotherapy response using the known clinical and histological variables.

Methods

We analyzed the whole-slide histopathology images, RNA-Seq, and proteomics data from 587 primary serous ovarian adenocarcinoma patients and developed a systematic algorithm to integrate histopathology and functional omics findings and to predict patients’ response to platinum-based chemotherapy.

Results

Our convolutional neural networks identified the cancerous regions with areas under the receiver operating characteristic curve (AUCs) > 0.95 and classified tumor grade with AUCs > 0.80. Functional omics analysis revealed that expression levels of proteins participated in innate immune responses and catabolic pathways are associated with tumor grade. Quantitative histopathology analysis successfully stratified patients with different response to platinum-based chemotherapy (P = 0.003).

Conclusions

These results indicated the potential clinical utility of quantitative histopathology evaluation in tumor cell detection and chemotherapy response prediction. The developed algorithm is easily extensible to other tumor types and treatment modalities.
An authoritative algorithm most appropriate for the prediction of pulmonary embolism in patients with AECOPD
Authors: Xiong Wei , Du He , Xu Mei , Ding Wei , Sun Jinyuan , Han Fengfeng , Guo Xuejun
Published: August 2020

Background

Contemporarily authoritative algorithms for the prediction of acute pulmonary embolism (PE) comprise the Standard algorithm, the Age-adjusted algorithm, the YEARS algorithm, the PERC algorithm, and the PEGeD algorithm. To date, little is known with respect to which algorithm is most appropriate for the PE prediction in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

Methods

The patients with AECOPD who underwent the confirmed chest imaging investigations of PE due to the likelihood of PE predicted by the Standard algorithm were retrospectively reviewed. The patients were reassessed by the other four algorithms to reveal which algorithm had the best diagnostic accuracy for the likelihood prediction of PE for patients with AECOPD.

Results

The results showed that the PEGeD algorithm(88.6, 80.7, 50.4, 97.0%, 4.591, 0.141, 0.693, 82.1%) performed better overall in the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, Youden index, and diagnostic accuracy, in comparison with the Age-adjusted algorithm (78.6, 74.1, 40.1, 94.0%, 3.034, 0.289, 0.527, 74.9%), the YEARS algorithm (71.4, 76.6, 40.3, 92.4%, 3.051, 0.373, 0.480,75.6%), the PERC algorithm (98.6, 1.6, 18.2, 83.3%, 1.002, 0.875, 0.002, 19.2%). The difference of number of patients who were necessary to undergo chest imaging examinations and missed diagnoses resulted from each algorithm between the PEGeD algorithm and the Standard algorithm, the Age-adjusted algorithm, the YEARS algorithm, as well as the PERC algorithm were [− 789 (− 68.1%), N/A], [− 42 (− 3.6%),-21 (− 1.8%)], [− 3 (− 0.3%),-36 (− 3.1%)],[− 771 (− 66.6%), 21 (1.8%)], respectively.

Conclusions

To date, the PEGeD algorithm is the most appropriate strategy among the authoritative algorithms for the likelihood prediction of pulmonary embolism in patients with AECOPD.
Correction to: Identification of prognosis-related genes and construction of multi-regulatory networks in pancreatic cancer microenvironment by bioinformatics analysis
Authors: Li Tong , Liu Qiaofei , Zhang Ronghua , Liao Quan , Zhao Yupei
Published: August 2020

An amendment to this paper has been published and can be accessed via the original article.
CircZFR functions as a sponge of miR-578 to promote breast cancer progression by regulating HIF1A expression
Authors: Chen Zhuo , Wang Fang , Xiong Youyi , Wang Nan , Gu Yuanting , Qiu Xinguang
Published: August 2020

Background

Breast cancer (BC) is the most common malignancy among women. Emerging studies have demonstrated that circular RNA (circRNA) zinc finger RNA binding protein (circZFR) serves as a crucial regulator in many human cancers. However, the role and mechanism of circZFR in BC tumorigenesis remain unclear.

Methods

The levels of circZFR, miR-578 and hypoxia-inducible factor 1α (HIF1A) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Cell viability, colony formation, apoptosis, migration and invasion capacities in vitro were determined by using the Cell Counting Kit-8 (CCK-8), standard colony formation, flow cytometry and transwell assays, respectively. Glucose uptake, lactate product and adenosine triphosphate (ATP) levels of cells in vitro were measured using the commercial human assay kits. Targeted relationships among circZFR, miR-578 and HIF1A in BC cell lines were verified by dual-luciferase reporter and RNA pulldown assays. Animal studies were performed to assess the effect of circZFR on tumor growth in vivo.

Results

Our data indicated that circZFR was overexpressed in BC tissues and cells, and the increased circZFR level predicted poor prognosis of BC patients. CircZFR silencing or miR-578 overexpression repressed BC cell viability, colony formation, migration, invasion, and glycolysis and enhanced cell apoptosis in vitro. CircZFR silencing also hampered tumor growth in vivo. Mechanistically, circZFR acted as a sponge of miR-578, and circZFR silencing hindered BC cell malignant behaviors by miR-578. HIF1A was a functional target of miR-578 in regulating BC cell viability, colony formation, migration, invasion, glycolysis and apoptosis in vitro. Furthermore, circZFR modulated HIF1A expression through sponging miR-578.

Conclusion

Our findings first identified that the silencing of circZFR suppressed BC malignant progression in vitro via the regulation of the miR-578/HIF1A axis, providing evidence for the crucial involvement of circZFR in BC pathogenesis.