bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiovascular outcomes in patients with chronic kidney disease and COVID-19: a multi-regional data-linkage study
Authors: Lambourg Emilie J. , Gallacher Peter J. , Hunter Robert W. , Siddiqui Moneeza , Miller-Hodges Eve , Chalmers James D. , Pugh Dan , Dhaun Neeraj , Bell Samira
Published: May 2022

Background

Data describing cardiovascular outcomes in patients with coronavirus disease 2019 (COVID-19) and chronic kidney disease (CKD) are lacking. We compared cardiovascular outcomes of patients with and without COVID-19, stratified by CKD status.

Methods

This retrospective, multi-regional data-linkage study utilised individual patient-level data from two Scottish cohorts. All patients tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Cohort 1 between 1 February 2020 and 31 March 2021 and in Cohort 2 between 28 February 2020 and 8 February 2021 were included.

Results

Overall, 86 964 patients were tested for SARS-CoV-2. There were 36 904 patients (mean±sdage 61±21 years; 58.1% women; 15.9% CKD; 10.1% COVID-19 positive) in Cohort 1 and 50 060 patients (mean±sdage 63±20 years; 62.0% women; 16.4% CKD; 9.1% COVID-19 positive) in Cohort 2. In CKD patients, COVID-19 increased the risk of cardiovascular death by more than two-fold within 30 days (cause-specific hazard ratio (csHR) meta-estimate 2.34, 95% CI 1.83–2.99) and by 57% at the end of study follow-up (csHR meta-estimate 1.57, 95% CI 1.31–1.89). Similarly, the risk of all-cause death in COVID-19 positiveversusnegative CKD patients was greatest within 30 days (HR 4.53, 95% CI 3.97–5.16). Compared with patients without CKD, those with CKD had a higher risk of testing positive (11.5%versus9.3%). Following a positive test, CKD patients had higher rates of cardiovascular death (11.1%versus2.7%), cardiovascular complications and cardiovascular hospitalisations (7.1%versus3.3%) than those without CKD.

Conclusions

COVID-19 increases the risk of cardiovascular and all-cause death in CKD patients, especially in the short-term. CKD patients with COVID-19 are also at a disproportionate risk of cardiovascular complications than those without CKD.
A systematic review with meta-analysis of biomarkers for detection of pulmonary arterial hypertension
Authors: Smits A. Josien , Botros Liza , Mol Marijke A.E. , Ziesemer Kirsten A. , Wilkins Martin R. , Vonk Noordegraaf Anton , Bogaard Harm Jan , Aman Jurjan
Published: May 2022

Rationale

The blood is a rich source of potential biomarkers for the diagnosis of idiopathic and hereditary pulmonary arterial hypertension (iPAH and hPAH, referred to as “PAH”). While a lot of biomarkers have been identified for PAH, the clinical utility of these biomarkers often remains unclear. Here, we performed an unbiased meta-analysis of published biomarkers to identify biomarkers with the highest performance for detection of PAH.

Methods

A literature search (in PubMed, Embase.com, Clarivate Analytics/Web of Science Core Collection and Wiley/Cochrane Library) was performed up to 28 January 2021. Primary end points were blood biomarker levels in PAHversusasymptomatic controls or patients suspected of pulmonary hypertension (PH) with proven normal haemodynamic profiles.

Results

149 articles were identified by the literature search. Meta-analysis of 26 biomarkers yielded 17 biomarkers that were differentially expressed in PAH and non-PH control subjects. Red cell distribution width, low density lipid-cholesterol, d-dimer, N-terminal prohormone of brain natriuretic protein (NT-proBNP), interleukin-6 (IL-6) and uric acid were biomarkers with the largest observed differences, largest sample sizes and a low risk of publication bias. Receiver operating characteristic curves and sensitivity/specificity analyses demonstrated that NT-proBNP had a high sensitivity, but low specificity for PAH. For the other biomarkers, insufficient data on diagnostic accuracy with receiver operating characteristic curves were available for meta-analysis.

Conclusion

This meta-analysis validates NT-proBNP as a biomarker with high sensitivity for PAH, albeit with low specificity. The majority of biomarkers evaluated in this meta-analysis lacked either external validation or data on diagnostic accuracy. Further validation studies are required as well as studies that test combinations of biomarkers to improve specificity.
Acoustic surveillance of cough for detecting respiratory disease using artificial intelligence
Authors: Gabaldón-Figueira Juan C. , Keen Eric , Giménez Gerard , Orrillo Virginia , Blavia Isabel , Doré Dominique Hélène , Armendáriz Nuria , Chaccour Juliane , Fernandez-Montero Alejandro , Bartolomé Javier , Umashankar Nita , Small Peter , Grandjean Lapierre Simon , Chaccour Carlos
Published: May 2022

Research question

Can smartphones be used to detect individual and population-level changes in cough frequency that correlate with the incidence of coronavirus disease 2019 (COVID-19) and other respiratory infections?

Methods

This was a prospective cohort study carried out in Pamplona (Spain) between 2020 and 2021 using artificial intelligence cough detection software. Changes in cough frequency around the time of medical consultation were evaluated using a randomisation routine; significance was tested by comparing the distribution of cough frequencies to that obtained from a model of no difference. The correlation between changes of cough frequency and COVID-19 incidence was studied using an autoregressive moving average analysis, and its strength determined by calculating its autocorrelation function (ACF). Predictors for the regular use of the system were studied using a linear regression. Overall user experience was evaluated using a satisfaction questionnaire and through focused group discussions.

Results

We followed-up 616 participants and collected >62 000 coughs. Coughs per hour surged around the time cohort subjects sought medical care (difference +0.77 coughs·h−1; p=0.00001). There was a weak temporal correlation between aggregated coughs and the incidence of COVID-19 in the local population (ACF 0.43). Technical issues affected uptake and regular use of the system.

Interpretation

Artificial intelligence systems can detect changes in cough frequency that temporarily correlate with the onset of clinical disease at the individual level. A clearer correlation with population-level COVID-19 incidence, or other respiratory conditions, could be achieved with better penetration and compliance with cough monitoring.
Current and novel treatment options for obstructive sleep apnoea
Authors: Randerath Winfried , de Lange Jan , Hedner Jan , Ho Jean Pierre T.F. , Marklund Marie , Schiza Sofia , Steier Jörg , Verbraecken Johan
Published: May 2022

Obstructive sleep apnoea is a challenging medical problem due to its prevalence, its impact on quality of life and performance in school and professionally, the implications for risk of accidents, and comorbidities and mortality. Current research has carved out a broad spectrum of clinical phenotypes and defined major pathophysiological components. These findings point to the concept of personalised therapy, oriented on both the distinct clinical presentation and the most relevant pathophysiology in the individual patient. This leads to questions of whether sufficient therapeutic options other than positive airway pressure (PAP) alone are available, for which patients they may be useful, if there are specific indications for single or combined treatment, and whether there is solid scientific evidence for recommendations. This review describes our knowledge on PAP and non-PAP therapies to address upper airway collapsibility, muscle responsiveness, arousability and respiratory drive. The spectrum is broad and heterogeneous, including technical and pharmaceutical options already in clinical use or at an advanced experimental stage. Although there is an obvious need for more research on single or combined therapies, the available data demonstrate the variety of effective options, which should replace the unidirectional focus on PAP therapy.
Assessment for residual disease after pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension
Authors: Butler Oisín , Ju Shinyoung , Hoernig Soeren , Vogtländer Kai , Bansilal Sameer , Heresi Gustavo A.
Published: May 2022

Objectives

Pulmonary endarterectomy (PEA) is recommended for eligible patients with chronic thromboembolic pulmonary hypertension (CTEPH) and is potentially curative. However, persistent/recurrent CTEPH post-PEA can occur. Here we describe symptom and diagnostic assessment rates for residual disease post-PEA and longitudinal diagnostic patterns before and after riociguat approval for persistent/recurrent CTEPH after PEA.

Methods

This US retrospective cohort study analysed MarketScan data (1 January 2002–30 September 2018) from patients who underwent PEA following a CTEPH/pulmonary hypertension (PH) claim with at least 730 days of continuous enrolment post-PEA. Data on pre-specified PH symptoms and the types and timings of diagnostic assessments were collected.

Results

Of 103 patients (pre-riociguat approval, n=55; post-riociguat approval, n=48), residual PH symptoms >3 months after PEA were reported in 89% of patients. Overall, 89% of patients underwent one or more diagnostic tests (mean 4.6 tests/patient), most commonly echocardiography (84%), with only 5% of patients undergoing right heart catheterisation (RHC). In the post-versuspre-riociguat approval subgroup, assessments were more specific for CTEPH with an approximately two-fold increase in 6-min walk distance andN-terminal prohormone of brain natriuretic protein measurements and ventilation/perfusion scans, and a four-fold increase in RHCs.

Conclusions

Low RHC rates suggest that many patients with PH symptoms post-PEA are not being referred for full diagnostic workup. Changes to longitudinal diagnostic patterns may indicate increased recognition of persistent/recurrent CTEPH post-PEA; however, there remains a need for greater awareness around the importance of continued follow-up for patients with residual PH symptoms post-PEA.
Post-Impact Motion Planning and Tracking Control for Autonomous Vehicles
Authors: Wang Cong , Wang Zhenpo , Zhang Lei , Yu Huilong , Cao Dongpu
Published: May 2022

There is an increasing awareness of the need to reduce traffic accidents and fatality due to vehicle collision. Post-impact hazards can be more serious as the driver may fail to maintain effective control after collisions. To avoid subsequent crash events and to stabilize the vehicle, this paper proposes a post-impact motion planning and stability control method for autonomous vehicles. An enabling motion planning method is proposed for post-impact situations by combining the polynomial curve and artificial potential field while considering obstacle avoidance. A hierarchical controller that consists of an upper and a lower controller is then developed to track the planned motion. In the upper controller, a time-varying linear quadratic regulator is presented to calculate the desired generalized forces. In the lower controller, a nonlinear-optimization-based torque allocation algorithm is proposed to optimally coordinate the actuators to realize the desired generalized forces. The proposed scheme is verified under comprehensive driving scenarios through hardware-in-loop tests.
Biclustering fMRI time series: a comparative study
Authors: Castanho Eduardo N. , Aidos Helena , Madeira Sara C.
Published: May 2022

Background

The effectiveness of biclustering, simultaneous clustering of rows and columns in a data matrix, was shown in gene expression data analysis. Several researchers recognize its potentialities in other research areas. Nevertheless, the last two decades have witnessed the development of a significant number of biclustering algorithms targeting gene expression data analysis and a lack of consistent studies exploring the capacities of biclustering outside this traditional application domain.

Results

This work evaluates the potential use of biclustering in fMRI time series data, targeting the Region × Time dimensions by comparing seven state-in-the-art biclustering and three traditional clustering algorithms on artificial and real data. It further proposes a methodology for biclustering evaluation beyond gene expression data analysis. The results discuss the use of different search strategies in both artificial and real fMRI time series showed the superiority of exhaustive biclustering approaches, obtaining the most homogeneous biclusters. However, their high computational costs are a challenge, and further work is needed for the efficient use of biclustering in fMRI data analysis.

Conclusions

This work pinpoints avenues for the use of biclustering in spatio-temporal data analysis, in particular neurosciences applications. The proposed evaluation methodology showed evidence of the effectiveness of biclustering in finding local patterns in fMRI time series data. Further work is needed regarding scalability to promote the application in real scenarios.
Postoperative but not preoperative depression is associated with cognitive impairment after cardiac surgery: exploratory analysis of data from a randomized trial
Authors: Lewis Choy , Dokucu Mehmet E. , Brown Charles H. , Balmert Lauren , Srdanovic Nina , Madhan Ashwin Shaan , Samra Sahej Singh , Csernansky John , Grafman Jordan , Hogue Charles W.
Published: May 2022

Background

In this study we hypothesize that depression is associated with perioperative neurocognitive dysfunction and altered quality of life one month after surgery.

Methods

Data were obtained as part of a study evaluating cerebral autoregulation monitoring for targeting arterial pressure during cardiopulmonary bypass. Neuropsychological testing was performed before surgery and one month postoperatively. Testing included the Beck Depression Inventory, a depression symptoms questionnaire (0–63 scale), as well as anxiety and quality of life assessments. Depression was defined as a Beck Depression Inventory score > 13.

Results

Beck Depression data were available from 320 patients of whom cognitive domain endpoints were available from 88–98% at baseline and 69–79% after surgery. This range in end-points data was due to variability in the availability of each neuropsychological test results between patients. Depression was present in 50 (15.6%) patients before surgery and in 43 (13.4%) after surgery. Baseline depression was not associated with postoperative domain-specific neurocognitive function compared with non-depressed patients. Those with depression one month after surgery, though, had poorer performance on tests of attention (p = 0.017), memory (p = 0.049), verbal fluency (p = 0.010), processing speed (p = 0.017), and fine motor speed (p = 0.014). Postoperative neurocognitive dysfunction as a composite outcome occurred in 33.3% versus 14.5% of patients with and without postoperative depression (p = 0.040). Baseline depression was associated with higher anxiety and lower self-ratings on several quality of life domains, these measures were generally more adversely affected by depression one month after surgery.

Conclusions

The results of this exploratory analysis suggests that preoperative depression is not associated with perioperative neurocognitive dysfunction, but depression after cardiac surgery may be associated with impairment in in several cognitive domains, a higher frequency of the composite neurocognitive outcome, and altered quality of life.

Trial Registration

www.clinicaltrials.gov, NCT00981474 (parent study).
Massive sympathetic nerve infiltration in advanced hepatic alveolar echinococcosis: a case report and review of the literature
Authors: Wang Zongding , Jiang Tiemin , Aji Tuerganaili , Wen Hao
Published: May 2022

Background

Alveolar echinococcosis is a zoonotic disease that mostly affects the liver, with vascular invasion and a protean clinical symptom. However, no reports of sympathetic nerve infiltration in hepatic alveolar echinococcosis have been reported. Here, we report a case of hepatic alveolar echinococcosis in a 33-year-old man. In this end-stage case, the lesion was heavily involved in the large vessels and biliary tract, and immunohistochemistry also incidentally revealed extensive nerve infiltration in the specimens after surgical treatment. Subsequently, neural classification was identified.

Case presentation

We herein report a case of advanced hepatic alveolar echinococcosis with macrovascular invasion and sympathetic nerve infiltration. In this case, inferior vena cava (IVC), the portal vein and bile duct were infiltrated. Ultimately, according to our experience, ex vivo liver resection and autotransplantation (ELRA) was the optimal treatment way to perform for this unresectable patient. Samples were collected from normal liver tissue, junction tissue and the lesion. Hematoxylin–eosin (HE) staining was used to confirm the diagnosis. Neural infiltration was observed by immunohistochemical staining with protein gene product 9.5 (PGP9.5). Fluorescence colocalization was determined with PGP9.5 and tyrosine hydroxylase (TH). These results suggest that a large amount of sympathetic nerve infiltration occurred at the junction.

Conclusion

This study suggests that advanced hepatic alveolar echinococcosis shows infiltrating growth, often invades the large vessels and biliary ducts, and may be accompanied by sympathetic nerve infiltration.
First case of a renal cyst infection caused by Desulfovibrio: a case report and literature review
Authors: Okamoto Yoshiki , Miyabe Yoei , Seki Momoko , Ushio Yusuke , Sato Keisuke , Kasama Eri , Akiyama Kenichi , Karasawa Kazunori , Uchida Keiko , Kikuchi Ken , Nitta Kosaku , Moriyama Takahito , Hoshino Junichi
Published: May 2022

Background

Genus Desulfovibrio species is a sulphate-reducing anaerobic gram-negative rod that resides in the human oral cavity and intestinal tract. It was reported as the causative pathogen of bacteraemia and abdominal infections, but not renal cyst infection, and Desulfovibrio fairfieldensis has higher pathogenicity than other Desulfovibrio species.

Case presentation

A 63-year-old man was on haemodialysis for end-stage renal failure due to autosomal dominant polycystic kidney disease. On admission, he had a persistent high-grade fever, right lumbar back pain, and elevated C-reactive protein levels. His blood and urine cultures were negative. He received ciprofloxacin and meropenem; however, there was no clinical improvement. Contrast-enhanced computed tomography and plain magnetic resonance imaging revealed a haemorrhagic cyst at the upper pole of the right kidney. The lesion was drained. Although the drainage fluid culture was negative, D. fairfieldensis was detected in a renal cyst using a polymerase chain reaction. After the renal cyst drainage, he was treated with oral metronidazole and improved without any relapse.

Conclusions

To the best of our knowledge, this is the first reported case of a renal cyst infection with Desulfovibrio species. D. fairfieldensis is difficult to detect, and polymerase chain reaction tests can detect this bacterium and ensure better management for a successful recovery.
Dissemination and implementation strategies for physical activity guidelines among adults with disability, chronic conditions, and pregnancy: a systematic scoping review
Authors: Morgan T. L. , Romani C. , Ross-White A. , Latimer-Cheung A. , Tomasone J. R.
Published: May 2022

Background

Physical activity guidelines for adults with disability, chronic conditions, and pregnancy (i.e., specific populations) have been developed to provide guidance for engaging in physical activity. However, specific populations remain considerably less physically active compared to the general population, presenting a knowledge-practice gap.

Purpose

The purpose of this systematic scoping review was to identify and evaluate strategies for disseminating and implementing physical activity guidelines among specific populations and/or stakeholders (e.g., healthcare professionals) in Canada.

Methods

Five search approaches (peer-reviewed literature databases, grey literature database, custom Google search engines, targeted web-based searches, and content expert consultation) identified records documenting and/or evaluating strategies that had been used to disseminate or implement guidelines from a predetermined list. Systematic and scoping review protocols were followed. Risk of bias assessments were conducted for all studies that evaluated strategies.

Results

Eighty-one records reported dissemination strategies (n = 42), implementation strategies (n = 28), or both (n = 11). Twenty-two studies reporting on 29 evaluated strategies were deemed “serious” or “high” risk of bias. Common guideline dissemination and implementation strategies are deliberated and recommendations for future practice are made.

Conclusions

Findings may inform future dissemination and implementation efforts for physical activity guidelines in Canada or similar countries.
Seroprevalence of SARS-CoV-2 antibody among urban Iranian population: findings from the second large population-based cross-sectional study
Authors: Zamani Mohammad , Poustchi Hossein , Mohammadi Zahra , Dalvand Sahar , Sharafkhah Maryam , Motevalian Seyed Abbas , Eslami Saeid , Emami Amir , Somi Mohammad Hossein , Yazdani-Charati Jamshid , Saki Nader , Karami Manoochehr , Najafi Farid , Mohebbi Iraj , Veisi Nasrollah , Hormati Ahmad , Pourfarzi Farhad , Ghadimi Reza , Ansari-Moghaddam Alireza , Sharifi Hamid , Roshandel Gholamreza , Mansour-Ghanaei Fariborz , Joukar Farahnaz , Shayanrad Amaneh , Eghtesad Sareh , Niavarani Ahmadreza , Delavari Alireza , Kaveh Soudeh , Feizesani Akbar , Markarian Melineh , Shafighian Fatemeh , Sadjadi Alireza , Darvishian Maryam , Malekzadeh Reza
Published: May 2022

Background

The first large serosurvey in Iran found a SARS-CoV-2 antibody seroprevalence of 17.1% among the general population in the first wave of the epidemic by April, 2020. The purpose of the current study was to assess the seroprevalence of COVID-19 infection among Iranian general population after the third wave of the disease.

Methods

This population-based cross-sectional study was conducted on 7411 individuals aged ≥10 years old in 16 cities across 15 provinces in Iran between January and March, 2021. We randomly sampled individuals registered in the Iranian electronic health record system based on their national identification numbers and invited them by telephone to a healthcare center for data collection. Presence of SARS-CoV-2-specific IgG and IgM antibodies was assessed using the SARS-CoV-2 ELISA kits. The participants were also asked about their recent COVID-19-related symptoms, including cough, fever, chills, sore throat, headache, dyspnea, diarrhea, anosmia, conjunctivitis, weakness, myalgia, arthralgia, altered level of consciousness, and chest pain. The seroprevalence was estimated after adjustment for population weighting and test performance.

Results

The overall population-weighted seroprevalence adjusted for test performance was 34.2% (95% CI 31.0-37.3), with an estimated 7,667,874 (95% CI 6,950,412-8,362,915) infected individuals from the 16 cities. The seroprevalence varied between the cities, from the highest estimate in Tabriz (39.2% [95% CI 33.0-45.5]) to the lowest estimate in Kerman (16.0% [95% CI 10.7-21.4]). In the 16 cities studied, 50.9% of the seropositive individuals did not report a history of symptoms suggestive of COVID-19, implying an estimation of 3,902,948 (95% CI 3,537,760-4,256,724) asymptomatic infected individuals.

Conclusions

Nearly one in three individuals were exposed to SARS-CoV-2 in the studied cities by March 2021. The seroprevalence increased about two-fold between April, 2020, and March, 2021.
Naringenin and cryptotanshinone shift the immune response towards Th1 and modulate T regulatory cells via JAK2/STAT3 pathway in breast cancer
Authors: Noori Shokoofe , Nourbakhsh Mitra , Imani Hossein , Deravi Niloofar , Salehi Niloufar , Abdolvahabi Zohreh
Published: May 2022

Background

Use of natural products has been proposed as an efficient method in modulation of immune system and treatment of cancers. The aim of this study was to investigate the potential of cryptotanshinone (CPT), naringenin, and their combination in modulating the immune response towards Th1 cells and the involvement of JAK2/STAT3 signaling pathway in these effects.

Methods

Mouse models of delayed type hypersensitivity (DTH) were produced and treated with naringenin and CPT. The proliferation of spleen cells were assessed by Bromodeoxyuridine (BrdU) assay. Flowcytometry and enzyme-linked immunosorbent assay (ELISA) tests were employed to evaluate subpopulation of T-lymphocytes and the levels of cytokines, respectively. The JAK/STAT signaling pathway was analyzed by Western blotting.

Results

We showed higher DTH, increased lymphocyte proliferation, decreased tumor growth and reduced JAK2/STAT3 phosphorylation in mice treated with naringenin and CPT. Moreover, a significant decline in the production of IL-4 and an upsurge in the production of IFN-γ by splenocytes were observed. Additionally, the population of intra-tumor CD4+CD25+Foxp3+T cells was significantly lower in naringenin + CPT treated animals than that in controls.

Conclusion

Naringenin-CPT combination could exert immunomodulatory effects, suggesting this combination as a novel complementary therapeutic regimen for breast cancer.
Effect of an endodontic e-learning application on students’ performance during their first root canal treatment on real patients: a pilot study
Authors: Färber Christoph Maria , Lemos Martin , Said Yekta-Michael Sareh
Published: May 2022

Background

E-learning has found its way into dental teaching in general and endodontic teaching in particular. The present study aimed to implement a newly developed multimedia learning application and assess its effect on students’ first root canal treatment on real patients. With the COVID-19 outbreak, the application’s performance was investigated during the pandemic.

Methods

A total of 138 students in the initial clinical endodontic course participated in this study. The control group (n = 49) followed the traditional curriculum, including practice on artificial teeth and face-to-face teaching events. In addition to the traditional curriculum, test group 1 (n = 54) had access to an endodontic e-learning application containing videos demonstrating artificial teeth and patient cases. With the COVID-19 outbreak, test group 2 (n = 35) had no face-to-face teaching; however, endodontic patient treatments were included. The quality of students’ first root canal treatment on real patients was compared using performance and radiographic assessment items. Statistical analysis was done using Kruskal–Wallis and chi-squared tests. Test groups received a questionnaire to assess the learning application. Test group 2 also completed a COVID-19-specific survey to measure students’ perceptions of how the pandemic affected their endodontic education.

Results

The results of endodontic treatments were significantly better for test group 1 (P < 0.001) and 2 (P < 0.001) than for the control group. Likewise, there were significantly fewer treatment errors in test group 1 (P < 0.001) and 2 (P < 0.001). No significant differences were found between test groups 1 and 2. Students of the test groups positively evaluated the e-learning application. Students of test group 2 expressed their fear of negative impacts on their course performance.

Conclusion

The e-learning application was well-received and seemed to improve endodontic education. The results imply that the quality of education may be maintained by implementing e-learning to compensate for face-to-face teaching. As no difference was found between online and face-to-face teaching, students’ and lecturers’ concerns that endodontic education is suffering because of the pandemic may be eased.
Exploration the role of a clinical supervisor to improve the professional skills of medical students: a content analysis study
Authors: Keshavarzi Mohammad Hasan , Azandehi Salimeh khalili , Koohestani Hamid Reza , Baradaran Hamid Reza , Hayat Ali Asghar , Ghorbani Ali Asghar
Published: May 2022

Background and purpose

Clinical supervision supports learners and paves the way for effective and efficient learning in clinical settings. This study aimed to explain the responsibilities of clinical supervisors in clinical education wards to improve the professional skills of medical students.

Materials and methods

In this qualitative study, we used the conventional content analysis approach. The sample consisted of 16 faculty members of medical sciences and medical graduates of Iranian universities. Purposeful sampling and semi-structured interviews were used to collect data. The Graneheim and Lundman method (2004) analyzed the data.

Results

From the analysis of interviews, 2 themes, 8 categories, and 18 subcategories were obtained. “Clinical supervisor responsibilities” as a theme includes the categories: “Creating motivation in learner”, “Learner’s need recognition”, “Performance evaluation”, “Creating learning opportunities”, and “Professional ethics education”. And, the sub-categories were: “Creating a supportive atmosphere”, “Task assignment”,“Understanding training needs”, “Understanding individual needs”, “Periodic evaluation”, “Proper feedback’, “Reduce work stress”, “Learner engagement’ , “Learning Facilitation”, “Attention to the patient’s treatment”, and “Ethical observance in relation to patients”.

As the second theme “Clinical supervisor characteristics” included the categories of: “Scientific competence”, “Leading role”, and “Ethical model”. Their sub-categories are clustered as: “Knowledge of educational concepts”, “Mastery of professional concepts”, “Effective communication skills”, “Understanding managerial concepts”, “High resilience”, “Career commitment “, and “social commitment” .

Conclusions

The clinical supervisor will improve the professional skills of medical students, which will improve the quality of services provided, train efficient graduates, and provide a safe and relaxing environment that leads to patient satisfaction.
Incentivizing performance in health care: a rapid review, typology and qualitative study of unintended consequences
Authors: Li Xinyu , Evans Jenna M.
Published: May 2022

Background

Health systems are increasingly implementing policy-driven programs to incentivize performance using contracts, scorecards, rankings, rewards, and penalties. Studies of these “Performance Management” (PM) programs have identified unintended negative consequences. However, no single comprehensive typology of the negative and positive unintended consequences of PM in healthcare exists and most studies of unintended consequences were conducted in England or the United States. The aims of this study were: (1) To develop a comprehensive typology of unintended consequences of PM in healthcare, and (2) To describe multiple stakeholder perspectives of the unintended consequences of PM in cancer and renal care in Ontario, Canada.

Methods

We conducted a rapid review of unintended consequences of PM in healthcare (n = 41 papers) to develop a typology of unintended consequences. We then conducted a secondary analysis of data from a qualitative study involving semi-structured interviews with 147 participants involved with or impacted by a PM system used to oversee 40 care delivery networks in Ontario, Canada. Participants included administrators and clinical leads from the networks and the government agency managing the PM system. We undertook a hybrid inductive and deductive coding approach using the typology we developed from the rapid review.

Results

We present a comprehensive typology of 48 negative and positive unintended consequences of PM in healthcare, including five novel unintended consequences not previously identified or well-described in the literature. The typology is organized into two broad categories: unintended consequences on (1) organizations and providers and on (2) patients and patient care. The most common unintended consequences of PM identified in the literature were measure fixation, tunnel vision, and misrepresentation or gaming, while those most prominent in the qualitative data were administrative burden, insensitivity, reduced morale, and systemic dysfunction. We also found that unintended consequences of PM are often mutually reinforcing.

Conclusions

Our comprehensive typology provides a common language for discourse on unintended consequences and supports systematic, comparable analyses of unintended consequences across PM regimes and healthcare systems. Healthcare policymakers and managers can use the results of this study to inform the (re-)design and implementation of evidence-informed PM programs.
Impact of pitavastatin on new-onset diabetes mellitus compared to atorvastatin and rosuvastatin: a distributed network analysis of 10 real-world databases
Authors: Seo Won-Woo , Seo Seung In , Kim Yerim , Yoo Jong Jin , Shin Woon Geon , Kim Jinseob , You Seng Chan , Park Rae Woong , Park Young Min , Kim Kyung-Jin , Rhee Sang Youl , Park Meeyoung , Jin Eun-Sun , Kim Sung Eun
Published: May 2022

Background

Statin treatment increases the risk of new-onset diabetes mellitus (NODM); however, data directly comparing the risk of NODM among individual statins is limited. We compared the risk of NODM between patients using pitavastatin and atorvastatin or rosuvastatin using reliable, large-scale data.

Methods

Data of electronic health records from ten hospitals converted to the Observational Medical Outcomes Partnership Common Data Model (n = 14,605,368 patients) were used to identify new users of pitavastatin, atorvastatin, or rosuvastatin (atorvastatin + rosuvastatin) for ≥ 180 days without a previous history of diabetes or HbA1c level ≥ 5.7%. We conducted a cohort study using Cox regression analysis to examine the hazard ratio (HR) of NODM after propensity score matching (PSM) and then performed an aggregate meta-analysis of the HR.

Results

After 1:2 PSM, 10,238 new pitavastatin users (15,998 person-years of follow-up) and 18,605 atorvastatin + rosuvastatin users (33,477 person-years of follow-up) were pooled from 10 databases. The meta-analysis of the HRs demonstrated that pitavastatin resulted in a significantly reduced risk of NODM than atorvastatin + rosuvastatin (HR 0.72; 95% CI 0.59–0.87). In sub-analysis, pitavastatin was associated with a lower risk of NODM than atorvastatin or rosuvastatin after 1:1 PSM (HR 0.69; CI 0.54–0.88 and HR 0.74; CI 0.55–0.99, respectively). A consistently low risk of NODM in pitavastatin users was observed when compared with low-to-moderate-intensity atorvastatin + rosuvastatin users (HR 0.78; CI 0.62–0.98).

Conclusions

In this retrospective, multicenter active-comparator, new-user, cohort study, pitavastatin reduced the risk of NODM compared with atorvastatin or rosuvastatin.
N6-methyladenosine methylation modification patterns reveal immune profiling in pancreatic adenocarcinoma
Authors: Xu Hao , Yin Lu , Xu Qianhui , Xiang Jingjing , Xu Rujun
Published: May 2022

Background

Several studies have revealed that N6-methyladenosine (m6A) regulation is involved in various biological processes and cancer progression. Nevertheless, the potential effects of m6A modifications in the tumor immune microenvironment (TIME) and on immune regulation in pancreatic adenocarcinoma (PAAD) remains unclear.

Methods

A consensus clustering algorithm was used to identify different m6A modification patterns and construct an m6A-associated gene signature based on 23 m6A regulators in PAAD. The CIBERSORT and ssGSEA algorithms were used to estimate the components of the immune cells in each sample. The PCA algorithm was used to develop the m6Ascore system for the evaluation of m6A modification patterns in each sample.

Results

Two m6A modification patterns with different biological properties and prognoses were identified in 176 PAAD patient samples. The features of TIME between the two patterns were similar, with two definite immune phenotypes: immune-inflamed and immune-excluded. Based on the m6A phenotype-associated signature genes, we constructed an m6Ascore system to investigate the m6A modification pattern of each sample, profile the dissection of physiological processes, immune infiltration, clinical prognosis, immunotherapy, and genetic variation. Patients with low m6Ascore scores had better clinical outcomes, enhanced immune infiltration, and lower expression of immunotherapeutic drug targets, such as CD274 and PDCD1LG2. Further research indicated that the m6Ascore and tumor mutation burden were significantly correlated, and patients with low m6Ascore had higher mutation rates in SMAD4 and TTN. Moreover, TNFRSF21 was significantly upregulated in PAAD tumor tissues and cell lines. Lower expression of TNFRSF21 had a prominent advantage in survival and was correlated with a low level of immune infiltration. PAAD samples with different TNFRSF21 expression levels showed significantly distinct sensitivities to chemotherapeutic agents.

Conclusions

This study revealed that m6A modification patterns could play an important role in the diversity and complexity of TIME, and the m6Ascore system could serve as an independent and powerful prognostic biomarker and is latently related to PAAD immunotherapies. Quantitative determination of m6A modification patterns in individual patients will be instrumental in mapping the TIME landscape and further optimizing precision immunotherapy.
Cutaneous reaction to ifosfamide plus mesna treated with desensitization challenge: a case report
Authors: Delgado-Prada Ana , Borrás Julián , Farzanegan Roxana , Torres Gorriz María Cruz , Germán-Sánchez Adrián , Cervera Aznar Raquel , Raducan Isabela , Castelló Jose Vicente , Sanchez-Hernandez Alfredo , Enrique Ernesto
Published: May 2022

Background

Ifosfamide is an alkylating agent used in the treatment of a wide range of tumours. Because of known side effects it is usually administered in combination with mesna, a thiol agent with uroprotective activity, to reduce them and increase the therapeutic dose. The most frequently administered regimens for ifosfamide are fractionated doses for 3 to 5 days, high-dose intravenous bolus, and continuous infusion over 24 to 72 h. Hypersensitivity reactions to ifosfamide plus mesna are not frequently described in the literature. Moreover, no reports exist concerning desensitization for this chemotherapy combination.

Case presentation

A 47-year-old man with stage IV renal sarcoma was treated with the combination of ifosfamide and mesna every 3 weeks in a 4-consecutive-day infusion protocol. During the second cycle of chemotherapy, he presented acute cutaneous symptoms. A 12-step desensitization protocol was proposed in view of the lack of knowledge of the possible hypersensitivity reactions to this combination of chemotherapy agents, and the multiple difficulties found during the study of the case.

Conclusions

The 12-step desensitization protocol was well tolerated. Therefore, it is an appropriate and safe option in the case of suspected allergy to ifosfamide plus mesna.
Tumor microenvironment responsive Mn3O4 nanoplatform for in vivo real-time monitoring of drug resistance and photothermal/chemodynamic synergistic therapy of gastric cancer
Authors: Li Hanrui , Cai Xiaoxia , Yi Tong , Zeng Yun , Ma Jingwen , Li Lei , Pang Liaojun , Li Na , Hu Hao , Zhan Yonghua
Published: May 2022

Background

Postoperative chemotherapy for gastric cancer often causes multidrug resistance (MDR), which has serious consequences for therapeutic effects. Individualized treatment based on accurate monitoring of MDR will greatly improve patient survival.

Results

In this article, a self-enhanced Mn3O4 nanoplatform (MPG NPs) was established, which can react with glutathione to produce Mn2+ to enhance T1-weighted magnetic resonance imaging (MRI) and mediate in vivo real-time MDR monitoring. In vitro MRI results showed that MRI signals could be enhanced in the presence of hydrogen peroxide and glutathione and at acidic pH. In vivo MRI results indicated that MPG NPs could specifically target MDR cells, thereby realizing real-time monitoring of MDR in gastric cancer. Furthermore, MPG NPs have good chemodynamic activity, which can convert the endogenous hydrogen peroxide of tumor cells into highly toxic hydroxyl radical through Fenton-like reaction at acidic pH to play the role of chemodynamic therapy. In addition, Mn3O4 can significantly enhance the chemodynamic therapy effect because of its good photothermal conversion effect. Furthermore, in situ photothermal/chemodynamic synergistic therapy obtained remarkable results, the tumors of the mice in the synergistic therapy group gradually became smaller or even disappeared.

Conclusions

MPG NPs have good biocompatibility, providing a good nanoplatform for real-time monitoring and precise diagnosis and treatment of MDR in gastric cancer.

Graphical Abstract
Tackling brain drain at Chinese CDCs: understanding job preferences of public health doctoral students using a discrete choice experiment survey
Authors: Liu Shimeng , Gu Yuanyuan , Yang Yi , Schroeder Elizabeth , Chen Yingyao
Published: May 2022

Background

Given the demands for public health and infectious disease management skills during COVID-19, a shortage of the public health workforce, particularly with skills and competencies in epidemiology and biostatistics, has emerged at the Centers for Disease Controls (CDCs) in China. This study aims to investigate the employment preferences of doctoral students majoring in epidemiology and biostatistics, to inform policy-makers and future employers to address recruitment and retention requirements at CDCs across China.

Methods

A convenience sampling approach for recruitment, and an online discrete choice experiment (DCE) survey instrument to elicit future employee profiles, and self-report of their employment and aspirational preferences during October 20 and November 12, 2020. Attributes included monthly income, employment location, housing benefits, children’s education opportunities, working environment, career promotion speed and bianzhi (formally established post).

Results

A total of 106 doctoral epidemiology and biostatistics students from 28 universities completed the online survey. Monthly income, employment location and bianzhi was of highest concern in the seven attributes measured, though all attributes were statistically significant and presented in the expected direction, demonstrating preference heterogeneity. Work environment was of least concern. For the subgroup analysis, employment located in a first-tier city was more likely to lead to a higher utility value for PhD students who were women, married, from an urban area and had a high annual family income. Unsurprisingly, when compared to single students, married students were willing to forgo more for good educational opportunities for their children. The simulation results suggest that, given our base case, increasing only monthly income from 10,000 ($ 1449.1) to 25,000 CNY ($ 3622.7) the probability of choosing the job in the third-tier city would increase from 18.1 to 53.8% (i.e., the location choice is changed).

Conclusion

Monthly income and employment location were the preferred attributes across the cohort, with other attributes then clearly ranked and delineated. A wider use of DCEs could inform both recruitment and retention of a public health workforce, especially for CDCs in third-tier cities where resource constraints preclude all the strategies discussed here.
Engaging people with lived experience on advisory councils of a national not-for-profit: an integrated knowledge translation case study of Heart & Stroke Mission Critical Area Councils
Authors: Lewis Krystina B. , Peter Nedra ,   Heart & Stroke Foundation of Canada, Faubert Christine , Harriman Mary Elizabeth , Lindsay Patrice , Simard Anne , Yip Cindy , Graham Ian D. , Kothari Anita
Published: May 2022

Background

In 2018, the Heart and Stroke Foundation of Canada transformed its approach to organizational strategic planning and priority-setting. The goal was to generate impact from bench to bedside to community, to improve the health of Canadians. It engaged researchers, clinician scientists, health systems leaders, and community members including people with lived experience (PWLE) on six Mission Critical Area (MCA) councils, each of which was co-chaired by a researcher or clinician scientist and a person with lived experience. Together, council members were tasked with providing advice to Heart & Stroke about the most relevant and impactful priorities of our time. The aim of this research was to explore the value of the MCA councils to Heart & Stroke, and to council members themselves. The research questions focused on understanding the process of managing and participating on the councils, the challenges and outcomes.

Methods

 Using an integrated knowledge translation approach, we conducted a case study with developmental evaluation over a 2-year time period (2018–2020). We collected qualitative data from various sources (Heart & Stroke team responsible for managing the councils, council co-chairs, council members, and key informants). We collected documents and analysed them for contextual background.

Results

 Participants noted that the MCA councils continuously evolved over the 2 years in various ways: from an uncertain direction to a concrete one, better integrating the voice of PWLE, and increased cohesiveness within and across MCA councils. This evolution was achieved in parallel with successes and challenges at three levels: the MCA councils and its members, Heart & Stroke, and Canadians. The MCA councils were disbanded in 2020, yet learnings, developments, initiatives and established partnerships remain as their legacy.

Conclusions

 Heart & Stroke’s intended objectives for the MCA councils, to promote engagement and dialogue among community members including PWLE, clinician scientists, and researchers, and to provide advice into Heart & Stroke’s strategic renewal process, were achieved. This collaborative structure and process for PWLE engagement within a community of multidisciplinary clinician scientists and researchers is possible yet requires flexibility, commitment to stakeholder relationship management, and considerable resources. These findings may be helpful for other not-for-profit and funding organizations interested in engaging the public and other stakeholders into their organizational activities.
The future of cancer immunotherapy for brain tumors: a collaborative workshop
Authors: Brown Christine E. , Bucktrout Samantha , Butterfield Lisa H. , Futer Olga , Galanis Evanthia , Hormigo Adilia , Lim Michael , Okada Hideho , Prins Robert , Marr Sara Siebel , Tanner Kirk
Published: May 2022

Harnessing the effector mechanisms of the immune system to combat brain tumors with antigen specificity and memory has been in research and clinical testing for many years. Government grant mechanisms and non-profit organizations have supported many innovative projects and trials while biotech companies have invested in the development of needed tools, assays and novel clinical approaches. The National Brain Tumor Society and the Parker Institute for Cancer Immunotherapy partnered to host a workshop to share recent data, ideas and identify both hurdles and new opportunities for harnessing immunotherapy against pediatric and adult brain tumors. Adoptively transferred cell therapies have recently shown promising early clinical results. Local cell delivery to the brain, new antigen targets and innovative engineering approaches are poised for testing in a new generation of clinical trials. Although several such advances have been made, several obstacles remain for the successful application of immunotherapies for brain tumors, including the need for more representative animal models that can better foreshadow human trial outcomes. Tumor and tumor microenvironment biopsies with multiomic analysis are critical to understand mechanisms of response and patient stratification, yet brain tumors are especially challenging for such biopsy collection. These workshop proceedings and commentary shed light on the status of immunotherapy in pediatric and adult brain tumor patients, including current research as well as opportunities for improving future efforts to bring immunotherapy to the forefront in the management of brain tumors.