bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple endocrinopathies, hypercalcaemia and pancreatitis following combined immune checkpoint inhibitor use- case report and review of literature
Authors: Newman Christine , Kgosidalwa Oratile , Hakami Osamah A. , Kennedy Carmel , Grogan Liam , Agha Amar 
Published: February 2021

Abstract
Background
Immune checkpoint inhibitors (ICIs) are a novel class of oncological agents which are used to treat a number of malignancies. To date seven agents have been approved by the Food and Drug Administration (FDA) to treat both solid and haematological malignancies. Despite their efficacy they have been associated with a number of endocrinopathies. We report a unique case of hypophysitis, thyroiditis, severe hypercalcaemia and pancreatitis following combined ICI therapy.

Case presentation
A 46-year old Caucasian female with a background history of malignant melanoma and lung metastases presented to the emergency department with lethargy, nausea, palpitations and tremors. She had been started on a combination of nivolumab and ipilimumab 24 weeks earlier. Initial investigations revealed thyrotoxicosis with a thyroid stimulating hormone (TSH) of < 0.01 (0.38–5.33) mIU/L, free T4 of 66.9 (7–16) pmol/.L. TSH receptor and thyroperoxidase antibodies were negative. She was diagnosed with thyroiditis and treated with a beta blocker. Six weeks later she represented with polyuria and polydipsia. A corrected calcium of 3.54 (2.2–2.5) mmol/l and parathyroid hormone (PTH) of 9 (10–65) pg/ml confirmed a diagnosis of non-PTH mediated hypercalcaemia. PTH-related peptide and 1, 25-dihydroxycholecalciferol levels were within the normal range. Cross-sectional imaging and a bone scan out ruled bone metastases but did reveal an incidental finding of acute pancreatitis – both glucose and amylase levels were normal. The patient was treated with intravenous hydration and zoledronic acid. Assessment of the hypothalamic-pituitary-adrenal (HPA) axis uncovered adrenocorticotrophic hormone (ACTH) deficiency with a morning cortisol of 17 nmol/L. A pituitary Magnetic Resonance Image (MRI) was unremarkable. Given her excellent response to ICI therapy she remained on ipilimumab and nivolumab. On follow-up this patient’s thyrotoxicosis had resolved without anti-thyroid mediations – consistent with a diagnosis of thyroiditis secondary to nivolumab use. Calcium levels normalised rapidly and remained normal. ACTH deficiency persisted, and she is maintained on oral prednisolone.

Conclusion
This is a remarkable case in which ACTH deficiency due to hypophysitis; thyroiditis; hypercalcaemia and pancreatitis developed in the same patient on ipilimumab and nivolumab combination therapy. We postulate that hypercalcaemia in this case was secondary to a combination of hyperthyroidism and secondary adrenal insufficiency.
Effectiveness of face-to-face, blended and e-learning in teaching the application of local anaesthesia: a randomised study
Authors: Bock Anna , Kniha Kristian , Goloborodko Evgeny , Lemos Martin , Rittich Anne Barbara , Möhlhenrich Stephan Christian , Rafai Nicole , Hölzle Frank , Modabber Ali 
Published: February 2021

Abstract
Background
Local anaesthesia plays a key role in many aspects of a dentist’s work. The required skills to perform anaesthesia successfully are acquired at university. To take advantage of the possibilities for new teaching formats, a blended learning concept for the local anaesthesia course was developed. The aim of the study was to compare the effectiveness of face-to-face, blended and e-learning in teaching in local anaesthesia by assessing students’ knowledge gain, performance of practical skills and satisfaction with the course.

Methods
All participants (n = 37) were randomly allocated into three groups. After acquiring the theoretical background in the blended learning, e-learning or lecture groups, a test to assess knowledge gain was performed. The performance of the practical skills was assessed in a small-group seminar. Student attitudes were evaluated with a questionnaire.

Results
The blended group showed significantly better results (mean = 17, SD =1.5) in theoretical knowledge gain than the other two groups (e-learning group: mean = 14.7, SD = 2.2; lecture group: mean = 14.8, SD =2.3). When comparing the results of the clinical skills assessment, there was no significant difference among all three groups (p > 0.017). The participants confirmed a high overall satisfaction with the course, in particular with the blended learning approach.

Conclusion
This study indicates that blended learning improves the learning outcome for theoretical knowledge in teaching local anaesthesia more than either face-to-face learning or e-learning alone. Furthermore, the blended learning approach is highly appreciated by the students. For acquiring practical skills, this study shows that blended learning is as effective as other teaching methods.
Digital tools in the informed consent process: a systematic review
Authors: Gesualdo Francesco , Daverio Margherita , Palazzani Laura , Dimitriou Dimitris , Diez-Domingo Javier , Fons-Martinez Jaime , Jackson Sally , Vignally Pascal , Rizzo Caterina , Tozzi Alberto Eugenio 
Published: February 2021

Abstract
Background
Providing understandable information to patients is necessary to achieve the aims of the Informed Consent process: respecting and promoting patients’ autonomy and protecting patients from harm. In recent decades, new, primarily digital technologies have been used to apply and test innovative formats of Informed Consent. We conducted a systematic review to explore the impact of using digital tools for Informed Consent in both clinical research and in clinical practice. Understanding, satisfaction and participation were compared for digital tools versus the non-digital Informed Consent process.

Methods
We searched for studies on available electronic databases, including Pubmed, EMBASE, and Cochrane. Studies were identified using specific Mesh-terms/keywords. We included studies, published from January 2012 to October 2020, that focused on the use of digital Informed Consent tools for clinical research, or clinical procedures. Digital interventions were defined as interventions that used multimedia or audio–video to provide information to patients. We classified the interventions into 3 different categories: video only, non-interactive multimedia, and interactive multimedia.

Results
Our search yielded 19,579 publications. After title and abstract screening 100 studies were retained for full-text analysis, of which 73 publications were included. Studies examined interactive multimedia (29/73), non-interactive multimedia (13/73), and videos (31/73), and most (34/38) studies were conducted on adults. Innovations in consent were tested for clinical/surgical procedures (26/38) and clinical research (12/38). For research IC, 21 outcomes were explored, with a positive effect on at least one of the studied outcomes being observed in 8/12 studies. For clinical/surgical procedures 49 outcomes were explored, and 21/26 studies reported a positive effect on at least one of the studied outcomes.

Conclusions
Digital technologies for informed consent were not found to negatively affect any of the outcomes, and overall, multimedia tools seem desirable. Multimedia tools indicated a higher impact than videos only. Presence of a researcher may potentially enhance efficacy of different outcomes in research IC processes. Studies were heterogeneous in design, making evaluation of impact challenging. Robust study design including standardization is needed to conclusively assess impact.
Methylenetetrahydrofolate reductase gene polymorphism, global DNA methylation and blood pressure: a population based study from North India
Authors: Yadav Suniti , Longkumer Imnameren , Joshi Shipra , Saraswathy Kallur Nava 
Published: February 2021

AbstractBackgroundHypertension is a complex disorder affected by gene-environment interactions. Methylenetetrahydrofolate reductase (MTHFR) gene is one of the genes in One Carbon Metabolic (OCM) pathway that affects both blood pressure and epigenetic phenomenon.MTHFRC677T gene polymorphism leads to reduced methylation capacity via increased homocysteine concentrations. Global DNA methylation (5mC%) also gets affected in conditions such as hypertension. However, no study is found to understand hypertension in terms of both genetics and epigenetics. The present study aims to understand the relation between methylation,MTHFRC677T gene polymorphism and hypertension. It also tries to understand relation (if any) between methylation and anti-hypertensive drugs.MethodsThis is a cross-sectional study where data were collected from a total of 1634 individuals of either sex in age group 35–65 years. Hypertensives (SBP ≥ 140 mm Hg and DBP ≥ 90 mm Hg) (on treatment/not on treatment) and absolute controls were 236 (cases) and 307 (controls), respectively. All the samples were subjected toMTHFRC677T gene polymorphism screening (PCR–RFLP) and global DNA methylation assay (ELISA based colorimetric assay). Results of both the analyses were obtained on 218 cases, 263 controls.ResultsMedian 5mC% was relatively lower among cases (p > 0.05) compared to controls, despite controlling for confounders (age, sex, smoking, alcohol, diet) (r2-0.92, p-0.08). Cases not on medication had significantly reduced 5mC% compared to controls (p < 0.05), despite adjusting for confounders (r2-0.857, p-0.01). Among cases (irrespective of treatment), there was a significant variation in 5mC% across the three genotypes i.e. CC, CT and TT, with no such variation among controls. Cases (not on medication) with TT genotype had significantly lower methylation levels compared to the TT genotype controls and cases (on medication) (p < 0.01).ConclusionGlobal DNA hypomethylation seems to be associated with hypertension and antihypertensive drugs seem to improve methylation. Hypertensive individuals with TT genotype but not on medication are more likely to be prone to global DNA hypomethylation. Important precursors in OCM pathway include micronutrients such as vitamin B-12, B-9 and B-6; their nutritional interventions (either dietary or supplement) may serve as strategies to prevent hypertension at population level. However, more epidemiological-longitudinal studies are needed for further validation.
Compound heterozygous variants in LAMC3 in association with posterior periventricular nodular heterotopia
Authors: De Angelis Carla , Byrne Alicia B. , Morrow Rebecca , Feng Jinghua , Ha Thuong , Wang Paul , Schreiber Andreas W. , Babic Milena , Taranath Ajay , Manton Nick , King-Smith Sarah L. , Schwarz Quenten , Arts Peer , Scott Hamish S. , Barnett Christopher 
Published: February 2021

Abstract
Background
Periventricular nodular heterotopia (PNH) is a malformation of cortical development characterized by nodules of abnormally migrated neurons. The cause of posteriorly placed PNH is not well characterised and we present a case that provides insights into the cause of posterior PNH.

Case presentation
We report a fetus with extensive posterior PNH in association with biallelic variants in LAMC3. LAMC3 mutations have previously been shown to cause polymicrogyria and pachygyria in the occipital cortex, but not PNH. The occipital location of PNH in our case and the proposed function of LAMC3 in cortical development suggest that the identified LAMC3 variants may be causal of PNH in this fetus.

Conclusion
We hypothesise that this finding extends the cortical phenotype associated with LAMC3 and provides valuable insight into genetic cause of posterior PNH.
CiliOPD: a ciliopathy-associated COPD endotype
Authors: Perotin Jeanne-Marie , Polette Myriam , Deslée Gaëtan , Dormoy Valérian 
Published: February 2021

AbstractThe pathophysiology of chronic obstructive pulmonary disease (COPD) relies on airway remodelling and inflammation. Alterations of mucociliary clearance are a major hallmark of COPD caused by structural and functional cilia abnormalities. Using transcriptomic databases of whole lung tissues and isolated small airway epithelial cells (SAEC), we comparatively analysed cilia-associated and ciliopathy-associated gene signatures from a set of 495 genes in 7 datasets including 538 non-COPD and 508 COPD patients. This bio-informatics approach unveils yet undescribed cilia and ciliopathy genes associated with COPD including NEK6 and PROM2 that may contribute to the pathology, and suggests a COPD endotype exhibiting ciliopathy features (CiliOPD).
Deploying triple artemisinin-based combination therapy (TACT) for malaria treatment in Africa: ethical and practical considerations
Authors: Tindana Paulina , de Haan Freek , Amaratunga Chanaki , Dhorda Mehul , van der Pluijm Rob W. , Dondorp Arjen M. , Cheah Phaik Yeong 
Published: February 2021

AbstractMalaria remains a major cause of morbidity and mortality in Africa, particularly in children under five years of age. Availability of effective anti-malarial drug treatment is a cornerstone for malaria control and eventual malaria elimination. Artemisinin-based combination therapy (ACT) is worldwide the first-line treatment for uncomplicated falciparum malaria, but the ACT drugs are starting to fail in Southeast Asia because of drug resistance. Resistance to artemisinins and their partner drugs could spread from Southeast Asia to Africa or emerge locally, jeopardizing the progress made in malaria control with the increasing deployment of ACT in Africa. The development of triple artemisinin-based combination therapy (TACT) could contribute to mitigating the risks of artemisinin and partner drug resistance on the African continent. However, there are pertinent ethical and practical issues that ought to be taken into consideration. In this paper, the most important ethical tensions, some implementation practicalities and preliminary thoughts on addressing them are discussed. The discussion draws upon data from randomized clinical studies using TACT combined with ethical principles, published literature and lessons learned from the introduction of artemisinin-based combinations in African markets.
An unusual case of Cardiobacterium valvarum causing aortic endograft infection and osteomyelitis
Authors: Hauser Eric G. , Nizamuddin Imran , Yarusi Brett B. , Krueger Karen M. 
Published: February 2021

Abstract
Background
HACEK (Haemophilus spp., Aggregatibacter spp., Cardiobacterium spp., Eikenella corrodens, and Kingella spp.) group organisms are responsible for 0.8% to 6% of all infective endocarditis cases, with Cardiobacterium spp. being the third most commonly implicated HACEK microorganism. Within this genus is Cardiobacterium valvarum (C. valvarum), a novel organism described in 2004. To date, only 15 cases of C. valvarum infection have been reported in the English-language literature, and have primarily been cases of infective endocarditis in patients with valvular disease. C. valvarum has not been reported to cause infections spreading to the surrounding bone.

Case presentation
We present a case of a 57-year-old man with a history of aortic dissection followed by aortic endograft replacement who presented with back pain. He was found to have radiographic evidence of an infected aortic endograft, along with vertebral osteomyelitis, discitis, and epidural phlegmon. Blood cultures identified C. valvarum as the causative organism. The patient was treated with ceftriaxone and surgical intervention was deferred due to the patient’s complex anatomy. His course was complicated by septic cerebral emboli resulting in cerebrovascular accident.

Conclusions
This case report highlights C. valvarum, a rare and emerging HACEK group microorganism that warrants consideration in high-risk patients with evidence of subacute infection and disseminated disease. While C. valvarum classically presents as infective endocarditis, extra-cardiac manifestations have also been described. As demonstrated in this case, endograft involvement and osteomyelitis may occur in rare circumstances.
Current status and related factors of turnover intention of primary medical staff in Anhui Province, China: a cross-sectional study
Authors: Chen Guimei , Sang Lingzhi , Rong Jian , Yan Huosheng , Liu Hongzhang , Cheng Jing , Wang Li , Ding Hong , Chen Ren 
Published: February 2021

Abstract
Background
The shortage of primary medical staff is an important issue in the management of health human resources, and it is also a problem that all countries in the world need to face together. Since 2009, China has implemented a new series of medical system reforms and the shortage and loss of primary medical staff have been alleviated accordingly. However, China has a large population and it is difficult to distribute health human resources evenly across regions. This study aimed to explore the current status of turnover intention and its relationship with psychological capital, social support, and job burnout, as well as how these factors influence turnover intention of primary medical staff in Anhui province, China.

Methods
Using structured questionnaires to collect data, including demographic characteristics, turnover intention, psychological capital, social support, and Chinese Maslach Burnout Inventory scale. A total of 1152 primary medical workers of Anhui were investigated. Data were analyzed by t-test, analysis of variance (ANOVA), Pearson correlation analysis, and multiple linear regression model.

Results
Total scores of turnover intention, psychological capital, social support, and job burnout of subjects were 14.15 ± 4.35, 100.09 ± 15.98, 64.93 ± 13.23 and 41.07 ± 9.437, respectively. Multiple linear regression showed the related factors of turnover intention were age, job position, work unit, and scores of job burnout. Pearson correlation showed psychological capital and social support were negatively correlated with turnover intention, while the score of job burnout was positively correlated with turnover intention.

Conclusion
The improvement of psychological capital and social support and the reduction of job burnout may play an important role in reducing turnover intention of primary medical staff. Primary medical managers should strengthen the humanistic care for primary medical staff, optimize the incentive mechanism, and improve internal management of medical institutions for stability.
Outcomes, mechanisms and contextual factors of positive psychology interventions for health workers: a systematic review of global evidence
Authors: Kletter Maartje , Harris Bronwyn , Brown Celia 
Published: February 2021

AbstractBackgroundInterventions using positive psychology (PP), which build on positive qualities of healthcare personnel and institutions, could potentially enhance organisational performance in healthcare. The aim of this systematic review was to identify if PP interventions have an impact on organisational performance of healthcare personnel, and if so, how this impact can be achieved. We developed a logic model to explain the impact of PP interventions on organisational performance.MethodsWe searched Web of Science, Medline, Psychinfo, Embase, Scopus and CINAHL (from inception until March 2019) and references of included articles to identify studies that evaluated the impact of a PP intervention for health personnel. Study quality was assessed using the SQUIRE checklist for quality improvement studies. Data were extracted about study details, setting, participants, intervention, method of evaluation and results. Outcomes, mechanisms and contexts were coded in nVivo. Data synthesis was guided by Lewis’ theory of the impact of PP interventions on organisational performance and Kneale et al.’s method for logic model development. Collected data were integrated into a logic model explaining initial inputs, processes, and intermediate outcomes of PP interventions that lead to improved organisational performance in healthcare settings.ResultsWe retrieved 4638 articles and identified five through references of included articles of which 29 studies (31 articles) met our inclusion criteria. Most articles were of low quality (n = 19) and outcome measures varied widely. We identified 54 different outcomes of PP interventions, including ‘improved well-being’ and ‘improved interaction and support’. Forty-nine mechanisms were identified including ‘recognising and reframing negative interpretations’. Twenty four contextual factors were identified of which seven acted as barriers. ‘Managerial support’ was a facilitator mentioned in eight studies. All identified outcomes, mechanisms and contextual factors were integrated into a logic model explaining how interventions using PP can impact organisational performance in healthcare.ConclusionFew identified outcomes were statistically significant, however, trends in both quantitative and qualitative outcomes show that PP interventions can increase well-being and interaction and support and thus improve organisational performance in healthcare. The developed logic model can be used in the implementation and evaluation of interventions using PP for health personnel.
Interprofessional collaboration among health professionals in cleft lip and palate treatment and care in the public health sector of South Africa
Authors: Hlongwa Phumzile , Rispel Laetitia C. 
Published: February 2021

Abstract
Background
Collaboration among different categories of health professionals is essential for quality patient care, especially for individuals with cleft lip and palate (CLP). This study examined interprofessional collaboration (IPC) among health professionals in all CLP specialised centres in South Africa’s public health sector.

Methods
During 2017, a survey was conducted among health professionals at all the specialised CLP centres in South Africa’s public health sector. Following informed consent, each member of the CLP team completed a self-administered questionnaire on IPC, using the Interprofessional Competency Framework Self-Assessment Tool. The IPC questionnaire consists of seven domains with 51 items: care expertise (8 items); shared power (4 items); collaborative leadership (10 items); shared decision-making (2 items); optimising professional role and scope (10 items); effective group function (9 items); and competent communication (8 items). STATA®13 was used to analyse the data. Descriptive analysis of participants and overall mean scores were computed for each domain and analysed using ANOVA. All statistical tests were conducted at 5% significance level.

Results
We obtained an 87% response rate, and 52 participants completed the questionnaire. The majority of participants were female 52% (n = 27); with a mean age of 41.9 years (range 22–72). Plastic surgeons accounted for 38.5% of all study participants, followed by speech therapists (23.1%), and professional nurses (9.6%). The lowest mean score of 2.55 was obtained for effective group function (SD + -0.50), and the highest mean score of 2.92 for care expertise (SD + -0.37). Explanatory factor analysis showed that gender did not influence IPC, but category of health professional predicted scores on the five categories of shared power (p = 0.01), collaborative leadership (p = 0.04), optimising professional role and scope (p = 0.03), effective group function (p = 0.01) and effective communication (p = 0.04).

Conclusion
The seven IPC categories could be used as a guide to develop specific strategies to enhance IPC among CLP teams. Institutional support and leadership combined with patient-centred, continuing professional development in multi-disciplinary meetings will also enrich IPC.