bluuebunny/crossref_metadata_2025 huggingface dataset:
From Fatigue Surveys to Survey Fatigue - Notes from Daily Hematology Practice
Authors: Matzdorff Axel , Rüffer Jens U. , Meyer Oliver
Published: February 2021

Background: Monitoring fever, pain, and nausea has become a daily routine in hematology and oncology practice. Fatigue is also common but thematized much less often. Therefore, guidelines and professional organizations recommend implementing fatigue assessment in daily oncology practice. The current deficits can be explained by diverging scientific concepts, inconsistent definitions, and lack of consensus on measurement and therapy. As a quality improvement initiative and first step towards better fatigue assessment we wanted to find out which fatigue questionnaire is best suited for our patients.

Methods: On two educational meetings on general oncology issues we invited patients and healthy controls to participate in an anonymous survey. We distributed three different fatigue questionnaires (Fatigue Assessment Scale - FAS, Functional Assessment of Cancer Therapy-Fatigue-Scale - FACT-F, EORTC questionnaire on cancer related fatigue - EORTC QLQ-FA12, one for each participant) and asked to rate the questionnaires on a 5-point scale (1= fitting best to 5 = not fitting). We also counted the number of questions that had been left blank.

Results: Seventy-seven of 90 questionnaires were returned (85%). The average approval rating of the FAS questionnaire was 2.3 (patients n=10, score 2.0; controls n=35, score 2.3), of EORTC QLQ-FA12 2.4 (patients n=8, score 2.4; controls n=8, score 2.4), and of FACT-F 2.1 (patients n=9, score 2.0; controls n=7, score 2.3). The percentage of questions that had been left blank with FAS was 0.5%, 3% with EORTC QLQ-FA12, and 14% with FACT-F.

Conclusion: This survey did not measure fatigue and we do not know how many of our patients had fatigue. Its purpose was to assess the acceptance of three different fatigue questionnaires. The unexpected finding was that the average rating of all three questionnaires was remarkably similar and close to neutral. The number of blanks was highest with the EORTC QLQ-FA12 questionnaire which had more items than the two others. One explanation could be, that participants do not value questionnaires when they are long ("survey fatigue"). Maybe participants perceive fatigue as a personal failure and do not want to reveal this on a questionnaire, particularly not when there is a chance that this goes into their patient file. Questionnaires were developed for scientific research but might not be the right instrument to thematize fatigue in the setting of a busy hemato-oncology practice.

Disclosures

Matzdorff: Novartis Oncology: Consultancy, Other: Honoraria paid to institution; Amgen GmbH: Consultancy, Other: Honoraria paid to institution; Grifols Deutschland GmbH: Consultancy, Other: Honoraria paid to institution; Swedish Orphan Biovitrium GmbH: Consultancy, Other: Honoraria paid to institution; UCB Biopharma SRL: Consultancy, Other: Honoraria paid to institution; Roche Pharma AG: Other: Family stockownership. Meyer:Grifols Germany: Consultancy, Honoraria; Amgen GmbH: Honoraria; Novartis Pharma GmbH: Honoraria.
Real-World Outcomes of Patients Treated with Single-Agent Ibrutinib for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): A Systematic Review and Meta-Analysis
Authors: Cheung Matthew C. , Amitai Irina
Published: February 2021

BACKGROUND: Ibrutinib improves progression-free survival (PFS) compared to chemo-immunotherapy in both previously untreated and relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; hereafter, CLL) patients. Adverse events, such as atrial fibrillation, bleeding and fungal infections, are the leading cause of drug discontinuation. Observational studies of real-world patients suggest that the rate of ibrutinib-related adverse events is higher in practice than in clinical trials. Dose reductions and drug discontinuations are more common, which may affect outcomes, although evidence has been conflicting.

OBJECTIVES: The objective of this study is to systematically review and synthesize real-world toxicity and tolerability of CLL patients on ibrutinib.

METHODS: Prospective and retrospective cohort studies and case series of patients with CLL treated with single agent ibrutinib as first or subsequent line treatment outside of clinical trials were retrieved from the Pubmed, Embase, and CENTRAL databases. Studies were critically appraised using Joanna-Briggs Institute checklists. Meta-analyses of studies deemed of moderate to high quality were done if the risk of heterogeneity was low.

RESULTS: We screened 4458 titles and abstracts and moved 251 records to full-text review. 25 full-text studies were included in the qualitative analysis. Most studies were of low to moderate quality. Rates of any bleeding ranged from 5.4 to 54.1 events/100 persons-year. Rates of severe bleeding ranged from 0 to 6.4 events/100 persons-year. Rate of infection was 9.2 to 49.8 infections/100 persons-year. Rate of atrial fibrillation varied from 2.5 to 26.0 events/100 persons-year. Pooled estimate of risk of atrial fibrillation per 100 person-years was 7.0 (95% CI 5.8, 8.2) by meta-analysis of moderate quality studies. Rate of dose reductions varied from 15.1 to 26.8 events/100 person-years, and dose reductions did not affect outcomes. The rate of drug discontinuation varied from 6.4 to 55.2 events/100 person-years. The most common cause for drug discontinuation was adverse events.

CONCLUSION: The risk of atrial fibrillation is higher in the real-world than reported from clinical trials. There was a large range of prevalence of other bleeding and infection. These adverse events were the leading cause of dose reduction and drug discontinuation. This study has many limitations arising from heterogeneity of patient characteristics and outcomes ascertainment. This highlights the need for standardized post-marketing studies of new drugs and for inclusive criteria for inclusion into randomized controlled trials.

Disclosures

No relevant conflicts of interest to declare.
Examination of Real-World Outcomes and Health Care Resource Utilization in the Prevention and Treatment of Tumor Lysis Syndrome
Authors: Balcerski Wynter , Chatterjee Kaustav , Barnes Yvonne J , Drea Ed
Published: February 2021

BACKGROUND AND OBJECTIVE: Tumor lysis syndrome (TLS), a potentially fatal oncologic complication, can have a significant clinical and economic impact to patients and the healthcare system. The aim of this poster is to examine real world healthcare resource utilization assessments in patients treated with rasburicase for the prevention or management of tumor lysis hyperuricemia.

METHODS: Four separate oncology E.H.R. database recent publications were selected for assessment of the prevention and treatment of hyperuricemia associated with TLS. The separate databases include data from 400 hospitals across 42 states, 14,383 newly-diagnosed lymphoma patients across 101 hospitals in a non-profit community oncology network, 21 healthcare organizations accounting for a total of 26 million patients, and 750,000 community oncology patients that includes 25,000 active OCM practices. The separate studies queried databases for patients at high risk of hyperuricemia of TLS inclusive of tumor diagnosis, uric acid, LDH, WBC, uricosuric agent, site of care, and health resource utilization such as hospitalization and length of stay.

RESULTS:

See Table

CONCLUSIONS: Across the findings from 4 separate retrospective, real-world studies assessing the prevention and management of hyperuricemia of TLS, the application of criteria for the identification of patients at intermediate or high risk are not universally applied. Recognition of clinical risk factors for hyperuricemia of TLS are needed for the timely and appropriate selection of therapy to prevent hyperuricemia of chemotherapy.

Table

Disclosures

Balcerski: Sanofi Genzyme: Current Employment. Chatterjee:Sanofi: Current Employment. Barnes:Sanofi: Current Employment. Drea:Sanofi/Genzyme: Current Employment.
Defective palmitoylation of transferrin receptor triggers iron overload in Friedreich ataxia fibroblasts
Authors: Petit Floriane , Drecourt Anthony , Dussiot Michaël , Zangarelli Coralie , Hermine Olivier , Munnich Arnold , Rötig Agnès
Published: February 2021

Friedreich ataxia (FRDA) is a frequent autosomal recessive disease caused by a GAA repeat expansion in the FXN gene encoding frataxin, a mitochondrial protein involved in iron-sulfur cluster (ISC) biogenesis. Resulting frataxin deficiency affects ISC-containing proteins and causes iron to accumulate in the brain and heart of FRDA patients. Here we report on abnormal cellular iron homeostasis in FRDA fibroblasts inducing a massive iron overload in cytosol and mitochondria. We observe membrane transferrin receptor 1 (TfR1) accumulation, increased TfR1 endocytosis, and delayed Tf recycling, ascribing this to impaired TfR1 palmitoylation. Frataxin deficiency is shown to reduce coenzyme A (CoA) availability for TfR1 palmitoylation. Finally, we demonstrate that artesunate, CoA, and dichloroacetate improve TfR1 palmitoylation and decrease iron overload, paving the road for evidence-based therapeutic strategies at the actionable level of TfR1 palmitoylation in FRDA.
Targeting of canonical WNT signaling ameliorates experimental sclerodermatous chronic graft-versus-host disease
Authors: Zhang Yun , Shen Lichong , Dreißigacker Katja , Zhu Honglin , Trinh-Minh Thuong , Meng Xianyi , Tran-Manh Cuong , Dees Clara , Matei Alexandru-Emil , Chen Chih-Wei , Ditschkowski Markus , Krauss Stefan , Winkler Julia , Wolff Daniel , Ziemer Mirjana , Beilhack Andreas , Karrer Sigrid , Herr Wolfgang , Mackensen Andreas , Schett Georg , Spriewald Bernd M. , Distler Jörg H. W.
Published: February 2021

Chronic graft-versus-host disease (cGVHD) is a major life-threatening complication of allogeneic hematopoietic stem cell transplantation. The molecular mechanisms underlying cGVHD remain poorly understood, and targeted therapies for clinical use are not well established. Here, we examined the role of the canonical WNT pathway in sclerodermatous cGVHD (sclGVHD). WNT signaling was activated in human sclGVHD with increased nuclear accumulation of the transcription factor β-catenin and a WNT-biased gene expression signature in lesional skin. Treatment with the highly selective tankryase inhibitor G007-LK, the CK1α agonist pyrvinium, or the LRP6 inhibitor salinomycin abrogated the activation of WNT signaling and protected against experimental cGVHD, without a significant impact on graft-versus-leukemia effect (GVL). Treatment with G007-LK, pyrvinium, or salinomycin almost completely prevented the development of clinical and histological features in the B10.D2 (H-2d) → BALB/c (H-2d) and LP/J (H-2b) → C57BL/6 (H-2b) models of sclGVHD. Inhibition of canonical WNT signaling reduced the release of extracellular matrix from fibroblasts and reduced leukocyte influx, suggesting that WNT signaling stimulates fibrotic tissue remodeling by direct effects on fibroblasts and by indirect inflammation-dependent effects in sclGVHD. Our findings may have direct translational potential, because pyrvinium is in clinical use, and tankyrase inhibitors are in clinical trials for other indications.
Structure of blood coagulation factor VIII in complex with an anti–C1 domain pathogenic antibody inhibitor
Authors: Gish Joseph S. , Jarvis Lexi , Childers Kenneth C. , Peters Shaun C. , Garrels Connor S. , Smith Ian W. , Spencer H. Trent , Doering Christopher B. , Lollar Pete , Spiegel P. Clint
Published: February 2021

Antibody inhibitor development in hemophilia A represents the most significant complication resulting from factor VIII (fVIII) replacement therapy. Recent studies have demonstrated that epitopes present in the C1 domain contribute to a pathogenic inhibitor response. In this study, we report the structure of a group A anti–C1 domain inhibitor, termed 2A9, in complex with a B domain–deleted, bioengineered fVIII construct (ET3i). The 2A9 epitope forms direct contacts to the C1 domain at 3 different surface loops consisting of Lys2065-Trp2070, Arg2150-Tyr2156, and Lys2110-Trp2112. Additional contacts are observed between 2A9 and the A3 domain, including the Phe1743-Tyr1748 loop and the N-linked glycosylation at Asn1810. Most of the C1 domain loops in the 2A9 epitope also represent a putative interface between fVIII and von Willebrand factor. Lastly, the C2 domain in the ET3i:2A9 complex adopts a large, novel conformational change, translocating outward from the structure of fVIII by 20 Å. This study reports the first structure of an anti–C1 domain antibody inhibitor and the first fVIII:inhibitor complex with a therapeutically active fVIII construct. Further structural understanding of fVIII immunogenicity may result in the development of more effective and safe fVIII replacement therapies.
The impact of neutrophil extracellular trap from patients with systemic lupus erythematosus on the viability, CD11b expression and oxidative burst of healthy neutrophils
Authors: Fatemi Alimohammad , Alipour Razieh , Khanahmad Hossein , Alsahebfosul Fereshteh , Andalib Alireza , Pourazar Abbasali
Published: February 2021

Background

NET (neutrophil extracellular trap) has been shown to directly influence inflammation; in SLE (systemic lupus erythematosus), it is reportedly a plausible cause for the broken self-tolerance that contributes to this pathology. Meanwhile, the role of NET is not easily explicable, and there is a serious discrepancy in the role of NET in SLE pathology and generally inflammation; in particular, the interactions of neutrophils with NET have been rarely inspected. This study evaluates the effect of NET on neutrophils in the context of SLE. The neutrophils were incubated by the collected NET (from SLE patients and healthy controls) and their expression of an activation marker, viability and oxidative burst ability were measured.

Results

The level of cell mortality, CD11b expression and the oxidative burst capacity were elevated in NET-treated neutrophils. Also, the elevation caused by the SLE NET was higher than that produced by the healthy NET.

Conclusion

The decreased neutrophil viability was not due to the increase in apoptosis; rather, it was because of the augmentation of other inflammatory cell-death modes. The upregulation of CD11b implies that NET causes neutrophils to more actively contribute to inflammation. The increased oxidative burst capacity of neutrophils can play a double role in inflammation. Overall, the effects induced by NET on neutrophils help prolong inflammation; accordingly, the NET collected from SLE patients is stronger than the NET from healthy individuals.
Development and validation of a predictive score for ICU delirium in critically ill patients
Authors: Zhang Huijuan , Yuan Jing , Chen Qun , Cao Yingya , Wang Zhen , Lu Weihua , Bao Juan
Published: February 2021

Background

The incidence of delirium in intensive care unit (ICU) patients is high and associated with a poor prognosis. We validated the risk factors of delirium to identify relevant early and predictive clinical indicators and developed an optimized model.

Methods

In the derivation cohort, 223 patients were assigned to two groups (with or without delirium) based on the CAM-ICU results. Multivariate logistic regression analysis was conducted to identify independent risk predictors, and the accuracy of the predictors was then validated in a prospective cohort of 81 patients.

Results

A total of 304 patients were included: 223 in the derivation group and 81 in the validation group, 64(21.1%)developed delirium. The model consisted of six predictors assessed at ICU admission: history of hypertension (RR = 4.367; P = 0.020), hypoxaemia (RR = 3.382; P = 0.018), use of benzodiazepines (RR = 5.503; P = 0.013), deep sedation (RR = 3.339; P = 0.048), sepsis (RR = 3.480; P = 0.018) and mechanical ventilation (RR = 3.547; P = 0.037). The mathematical model predicted ICU delirium with an accuracy of 0.862 (P < 0.001) in the derivation cohort and 0.739 (P < 0.001) in the validation cohort. No significant difference was found between the predicted and observed cases of ICU delirium in the validation cohort (P > 0.05).

Conclusions

Patients’ risk of delirium can be predicted at admission using the early prediction score, allowing the implementation of early preventive interventions aimed to reduce the incidence and severity of ICU delirium.
Implementing ERAS: how we achieved success within an anesthesia department
Authors: Ellis Dan B. , Agarwala Aalok , Cavallo Elena , Linov Pam , Hidrue Michael K. , del Carmen Marcela G. , Sisodia Rachel
Published: February 2021

Background

The Massachusetts General Hospital is a large, quaternary care institution with 58 operating rooms, 164 anesthesiologists, 76 certified nurse anesthetists (CRNAs), an anesthesiology residency program that admits 25 residents annually, and 35 surgeons who perform laparoscopic, vaginal, and open hysterectomies. In March of 2018, our institution launched an Enhanced Recovery After Surgery (ERAS) pathway for patients undergoing hysterectomy. To implement the anesthesia bundle of this pathway, an intensive 14-month educational endeavor was created and put into effect. There were no subsequent additional educational interventions.

Methods

We retrospectively reviewed records of 2570 patients who underwent hysterectomy between October 2016 and March 2020 to determine adherence to the anesthesia bundle of the ERAS Hysterectomy pathway. RESULTS: Increased adherence to the four elements of the anesthesia bundle (p < 0.001) was achieved during the intervention period. Compliance with the pathway was sustained in the post-intervention period despite no additional actions.

Conclusions

Implementing the anesthesia bundle of an ERAS pathway in a large anesthesia group with diverse providers successfully occurred using implementation science-based approach of intense interventions, and these results were maintained after the intervention ceased.
Experiences of supporting older persons in completion of an exercise and nutrition intervention: an interview study with nursing home staff
Authors: Vikström S. , Grönstedt H. K. , Cederholm T. , Franzén E. , Faxén-Irving G. , Seiger Å. , Boström A.-M.
Published: February 2021

Background

The interactions between nursing home (NH) staff and their residents are crucial not only for the atmosphere at the NH but also for achieving care goals. In order to test the potential effects of daily physical activities (sit-to-stand (STS) exercises) combined with oral nutritional supplementation (ONS), a randomized intervention trial (the Older Person’s Exercise and Nutrition (OPEN) Study) was performed in NH residents. One aspect of the study was to interview and report the NH staff’s experiences of supporting the residents in fulfilling the intervention.

Methods

In this qualitative study, individual and focus group interviews were performed in eight NH facilities with NH staff who had assisted residents in performing the 12-week ONS/STS intervention. An interview guide developed for this study was used to assess staff experiences of the intervention and its feasibility. The transcribed interviews were analyzed inductively following a constant comparative method and with input from experts in the area, described in Grounded Theory as a reliable technique for researchers to form theory and hypothesis in unexplored areas.

Results

Three main themes relating to the health-promoting intervention emerged. These included: 1) insights into attitudes towards health in general and NH care specifically; 2) intervention-related challenges, frustrations and needs, and 3) aspects of collaboration and opportunities.

The overarching hypothesis derived from the analysis reads: A health-promoting intervention such as the OPEN-concept has great potential for integration into NH life if a combined empathic and encouraging attitude, and a structure to keep it sustainable, are in place.

Conclusions

NH staff experienced the health-promoting intervention as a potentially positive concept, although it was suggested that it works best if introduced as a general routine in the unit and is integrated into the daily planning of care.

Trial registration

ClinicalTrials.govIdentifier: NCT02702037. Date of trial registration February 26, 2016. The trial was registered prospectively
Accuracy of whole-body diffusion-weighted MRI (WB-DWI/MRI) in diagnosis, staging and follow-up of gastric cancer, in comparison to CT: a pilot study
Authors: De Vuysere Sofie , Vandecaveye Vincent , De Bruecker Yves , Carton Saskia , Vermeiren Koen , Tollens Tim , De Keyzer Frederik , Dresen Raphaëla Carmen
Published: February 2021

Background

Accurate staging of patients with gastric cancer is necessary for selection of the most appropriate and personalized therapy. Computed tomography (CT) is currently used as primary staging tool, being widely available with a relatively high accuracy for the detection of parenchymal metastases, but with low sensitivity for the detection of peritoneal metastases. Magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) has a very high contrast resolution, suggesting a higher diagnostic performance in the detection of small peritoneal lesions. The aim of this study was to retrospectively evaluate the added value of whole-body diffusion-weighted MRI (WB-DWI/MRI) to CT for detection of peritoneal carcinomatosis (PC) and distant metastases in the preoperative staging of gastric cancer.

Methods

This retrospective study included thirty-two patients with a suspicion of gastric cancer/recurrence, who underwent WB-DWI/MRI at 1.5 T, in addition to CT of thorax and abdomen. Images were evaluated by two experienced abdominal radiologists in consensus. Histopathology, laparoscopy and/or 1-year follow-up were used as reference standard.

Results

For overall tumour detection (n = 32), CT sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) was 83.3%, 100%, 100% and 82.4% respectively. For WB-DWI/MRI these values were 100%, 92.9%, 94.7% and 100%, respectively. For staging (n = 18) malignant lymph nodes and metastases, CT had a sensitivity, specificity/PPV/NPV of 50%/100%/100%/71.4%, and 15.4%/100%/100%/31.3% respectively. For WB-DWI/MRI, all values were 100%, for both malignant lymph nodes and metastases. WB-DWI/MRI was significantly better than CT in detecting tumour infiltration of the mesenteric root, serosal involvement of the small bowel and peritoneal metastases for which WB-DWI/MRI was correct in 100% of these cases, CT 0%.

Conclusions

WB-DWI/MRI is highly accurate for diagnosis, staging and follow-up of patients with suspected gastric cancer.
Atypical anti-glomerular basement membrane disease with anti-GBM antibody negativity and ANCA positivity: a case report
Authors: Guo Na , Yin Qinghua , Lei Song , He Yanjun , Fu Ping
Published: February 2021

Background

Anti-glomerular basement membrane (anti-GBM) disease is an organ-specific autoimmune disease that involves the lung and kidneys and leads to rapid glomerulonephritis progression, with or without diffuse alveolar hemorrhage, and even respiratory failure. Classic cases of anti-GBM disease are diagnosed based on the presence of the anti-GBM antibody in serum samples and kidney or lung biopsy tissue samples. However, atypical cases of anti-GBM disease are also seen in clinical practice.

Case presentation

We herein report the rare case of a patient with atypical anti-GBM disease whose serum was negative for the anti-GBM antibody but positive for the myeloperoxidase (MPO) anti-neutrophil cytoplasmic antibody (p-ANCA) and another atypical ANCA. Laboratory test results showed severe renal insufficiency with a creatinine level of 385 μmol/L. Renal biopsy specimen analysis revealed 100% glomeruli with crescents; immunofluorescence showed immunoglobulin G (IgG) linearly deposited alongside the GBM. Finally, the patient was discharged successfully after treatment with plasmapheresis, methylprednisolone and prednisone.

Conclusion

This patient, whose serum was negative for the anti-GBM antibody but positive for p-ANCA and another atypical ANCA, had a rare case of anti-GBM disease. Insights from this unusual case might help physicians diagnose rare forms of glomerulonephritis and treat affected patients in a timely manner.
Systematic review and subgroup analysis of the incidence of acute kidney injury (AKI) in patients with COVID-19
Authors: Xu Zhenjian , Tang Ying , Huang Qiuyan , Fu Sha , Li Xiaomei , Lin Baojuan , Xu Anping , Chen Junzhe
Published: February 2021

Background

Acute kidney injury (AKI) occurs among patients with coronavirus disease-19 (COVID-19) and has also been indicated to be associated with in-hospital mortality. Remdesivir has been authorized for the treatment of COVID-19. We conducted a systematic review to evaluate the incidence of AKI in hospitalized COVID-19 patients. The incidence of AKI in different subgroups was also investigated.

Methods

A thorough search was performed to find relevant studies in PubMed, Web of Science, medRxiv and EMBASE from 1 Jan 2020 until 1 June 2020. The systematic review was performed using the meta package in R (4.0.1).

Results

A total of 16,199 COVID-19 patients were included in our systematic review. The pooled estimated incidence of AKI in all hospitalized COVID-19 patients was 10.0% (95% CI: 7.0–12.0%). The pooled estimated proportion of COVID-19 patients who needed continuous renal replacement therapy (CRRT) was 4% (95% CI: 3–6%). According to our subgroup analysis, the incidence of AKI could be associated with age, disease severity and ethnicity. The incidence of AKI in hospitalized COVID-19 patients being treated with remdesivir was 7% (95% CI: 3–13%) in a total of 5 studies.

Conclusion

We found that AKI was not rare in hospitalized COVID-19 patients. The incidence of AKI could be associated with age, disease severity and ethnicity. Remdesivir probably did not induce AKI in COVID-19 patients. Our systematic review provides evidence that AKI might be closely associated with SARS-CoV-2 infection, which should be investigated in future studies.
Abnormal regional homogeneity and its relationship with symptom severity in cervical dystonia: a rest state fMRI study
Authors: Wei Shubao , Lu Chunhui , Chen Xiuqiong , Yang Lu , Wei Jing , Jiang Wenyan , Liu Yang , Li Hui Hui , Qin Yuhong , Lei Yiwu , Qin Chao , Hu Caiyou , Luo Shuguang
Published: February 2021

Background

Although several brain networks play important roles in cervical dystonia (CD) patients, regional homogeneity (ReHo) changes in CD patients have not been clarified. We investigated to explore ReHo in CD patients at rest and analyzed its correlations with symptom severity as measured by Tsui scale.

Methods

A total of 19 CD patients and 21 gender-, age-, and education-matched healthy controls underwent fMRI scans at rest state. Data were analyzed by ReHo method.

Results

Patients showed increased ReHo in the right cerebellum crus I and decreased ReHo in the right superior medial prefrontal cortex (MPFC). Moreover, the right precentral gyrus, right insula, and bilateral middle cingulate gyrus also showed increased ReHo values. A significantly positive correlation was observed between ReHo value in the right cerebellum crus I and symptom severity (p < 0.05).

Conclusions

Our investigation suggested abnormal ReHo existed in brain regions of the “pain matrix” and salience network (the right insula and bilateral middle cingulate gyrus), the motor network (the right precentral gyrus), the cerebellum and MPFC and further highlighted the significance of these networks in the pathology of CD.
Composite adverse outcomes in obstetric studies: a systematic review
Authors: Herman Dylan , Lor Kar Yee , Qadree Abdul , Horn Daphne , D’Souza Rohan
Published: February 2021

Background

Composite outcomes are increasingly being used in obstetric trials. The aim of this systematic review is to critically appraise the use of composite outcomes in obstetric RCTs with an intention of identifying limitations and providing potential solutions for future research.

Methods

The study protocol was prospectively registered. Medline, Embase, Cochrane Databases and www.clinicaltrials.gov were searched for randomized controlled trials (RCTs) published in English between 1999 and 2019, using search terms related to pregnancy and composite outcomes. Study eligibility criteria: RCTs involving an obstetric condition that reported on a composite outcome. Study appraisal and synthesis methods: Screening and data extraction were performed in duplicate, and a descriptive synthesis and critical appraisal of composite obstetric outcomes, is presented.

Results

Of the 4170 results screened, we identified 156 RCTs, reporting on 181 composite outcomes. Of these, 158 composite outcomes related to general morbidity and mortality, either exclusively maternal (n=20), fetal-neonatal [perinatal] (n=116) or maternal and perinatal (n=22) were included in the final analysis. Obstetric composite outcomes included between two and 16 components. Components that comprised these composite outcomes were often dissimilar in terms of severity and frequency of occurrence, unlikely to have similar relative risk reductions and sometimes unrelated to the study’s primary objective – important pre-requisites to consider while constructing composite outcomes. In addition, composite adverse obstetric outcomes often do not incorporate the perspectives of pregnant persons, embrace a holistic view of health or consider outcomes related to both members of the mother-fetus dyad.

Conclusions

Composite outcomes are being increasingly used as primary outcomes in obstetric RCTs, based on which study conclusions are drawn and clinical recommendations made. However, there is a lack of consistency with regard to what components should be included within a composite adverse obstetric outcome and how these components should be measured. The use of novel research methods such as concept mapping may be able to address some of the limitations with the development of composite adverse obstetric outcomes, to inform future research.
Macular perfusion analysed by optical coherence tomography angiography after uncomplicated phacoemulsification: benefits beyond restoring vision
Authors: Križanović Ana , Bjeloš Mirjana , Bušić Mladen , Elabjer Biljana Kuzmanović , Rak Benedict , Vukojević Nenad
Published: February 2021

Background

The purpose of the study is to investigate the changes of macular perfusion by OCT-angiography (OCT-A) after uncomplicated phacoemulsification.

Methods

OCT-A was performed before cataract surgery, 1 week, 1 month, and 3 months after surgery recording superficial vascular complex (SVC), nerve fiber layer vascular plexus (NFLVP), superficial vascular plexus (SVP), deep vascular complex (DVC), intermediate capillary plexus (ICP) and deep capillary plexus (DCP), as well as large choroidal blood vessels and choriocapillaris (CC). Explant area (EA), vessels area (VA), vessels percentage area (VPA), total number of junctions (TNJ), junctions density (JD), total vessels length (TVL), average vessels length (AVL), total number of end points (TNEP), and mean lacunarity (ML) throughout all layers were analysed.

Results

Significant changes of vascular parameters in 55 eyes of 55 patients mostly reached plateau one week after surgery and remained stable up to 3 m after surgery, occurring in all retinal layers but not in choroid and CC. The greatest increase in VPA (22.79%), TVL (16.71%), AVL (166.71%) and JD (29.49%) was in SVC. On the contrary, the greatest change of ML (− 53.41%) appeared in DVC.

Conclusions

This is the first OCT-A study demonstrating perfusion alterations in macula after phacoemulsification due to functional hyperaemia. We presume the effect is evoked by increased light intensity stimulation of retina after cataract removal. Accordingly, phacoemulsification in elderly population could have advantageous feature in addition to restoring visual acuity.
Effect of real-time ultrasound imaging for biofeedback on trunk muscle contraction in healthy subjects: a preliminary study
Authors: Lin Shanshan , Zhu Bo , Zheng Yiyi , Huang Guozhi , Zeng Qing , Wang Chuhuai
Published: February 2021

Background

Real-time ultrasound imaging (RUSI) has been increasingly used as a form of biofeedback when instructing and re-training muscle contraction. However, the effectiveness of the RUSI on a single sustained contraction of the lumbar multifidus (LM) and transversus abdominis (TrA) has rarely been reported. This preliminary study aimed to determine if the use of RUSI, as visual biofeedback, could enhance the ability of activation and continuous contraction of the trunk muscles including LM and TrA.

Methods

Forty healthy individuals were included and randomly assigned into the experimental group and control group. All subjects performed a preferential activation of the LM and/or TrA (maintained the constraction of LM and/or TrA for 30 s and then relaxed for 2 min), while those in the experimental group also received visual feedback provided by RUSI. The thickness of LM and/or TrA at rest and during contraction (Tc-max, T15s, and T30s) were extracted and recorded. The experiment was repeated three times.

Results

No significant differences were found in the thickness of LM at rest (P > 0.999), Tc-max (P > 0.999), and T15s (P = 0.414) between the two groups. However, the ability to recruit LM muscle contraction differed between groups at T30s (P = 0.006), with subjects in the experimental group that received visual ultrasound biofeedback maintaining a relative maximum contraction. Besides, no significant differences were found in the TrA muscle thickness at rest (P > 0.999) and Tc-max (P > 0.999) between the two groups. However, significant differences of contraction thickness were found at T15s (P = 0.031) and T30s (P = 0.010) between the two groups during the Abdominal Drawing-in Maneuver (ADIM), with greater TrA muscle contraction thickness in the experimental group.

Conclusions

RUSI can be used to provide visual biofeedback, which can promote continuous contraction, and improve the ability to activate the LM and TrA muscles in healthy subjects.
Mitigating saliva aerosol contamination in a dental school clinic
Authors: Yang Maobin , Chaghtai Asad , Melendez Marc , Hasson Hana , Whitaker Eugene , Badi Mustafa , Sperrazza Leona , Godel Jeffrey , Yesilsoy Cemil , Tellez Marisol , Orrego Santiago , Montoya Carolina , Ismail Amid
Published: February 2021

Background

Transmission of COVID-19 via salivary aerosol particles generated when using handpieces or ultrasonic scalers is a major concern during the COVID-19 pandemic. The aim of this study was to assess the spread of dental aerosols on patients and dental providers during aerosol-generating dental procedures.

Methods

This pilot study was conducted with one volunteer. A dental unit used at the dental school for general dental care was the site of the experiment. Before the study, three measurement meters (DustTrak 8534, PTrak 8525 and AeroTrak 9306) were used to measure the ambient distribution of particles in the ambient air surrounding the dental chair. The volunteer wore a bouffant, goggles, and shoe covers and was seated in the dental chair in supine position, and covered with a surgical drape. The dentist and dental assistant donned bouffant, goggles, face shields, N95 masks, surgical gowns and shoe covers. The simulation was conducted by using a high-speed handpiece with a diamond bur operating in the oral cavity for 6 min without touching the teeth. A new set of measurement was obtained while using an ultrasonic scaler to clean all teeth of the volunteer. For both aerosol generating procedures, the aerosol particles were measured with the use of saliva ejector (SE) and high-speed suction (HSS) followed a separate set of measurement with the additional use of an extra oral high-volume suction (HVS) unit that was placed close to the mouth to capture the aerosol in addition to SE and HSS. The distribution of the air particles, including the size and concentration of aerosols, was measured around the patient, dentist, dental assistant, 3 feet above the patient, and the floor.

Results

Four locations were identified with elevated aerosol levels compared to the baseline, including the chest of the dentist, the chest of patient, the chest of assistant and 3 feet above the patient. The use of additional extra oral high volume suction reduced aerosol to or below the baseline level.

Conclusions

The increase of the level of aerosol with size less than 10 µm was minimal during dental procedures when using SE and HSS. Use of HVS further reduced aerosol levels below the ambient levels.
An innovative pharmacology curriculum for medical students: promoting higher order cognition, learner-centered coaching, and constructive feedback through a social pedagogy framework
Authors: McHugh Douglas , Yanik Andrew J. , Mancini Michael R.
Published: February 2021

Background

Ongoing developments in medical education recognize the move to curricula that support self-regulated learning processes, skills of thinking, and the ability to adapt and navigate uncertain situations as much as the knowledge base of learners. Difficulties encountered in pursuing this reform, especially for pharmacology, include the tendency of beginner learners not to ask higher-order questions and the potential incongruency between creating authentic spaces for self-directed learning and providing external expert guidance. We tested the feasibility of developing, implementing, and sustaining an innovative model of social pedagogy as a strategy to address these challenges.

Methods

Constructivism, communities of practice, and networked learning theory were selected as lenses for development of the model. Three hundred sixty-five first-year medical students participated between 2014 and 2018; they were introduced to pharmacodynamics and pharmacokinetics via 15 online modules that each included: learning objectives, a clinical vignette, teaching video, cumulative concept map, and small group wiki assignment. Five-person communities organized around the 15 wiki assignments were a key component where learners answered asynchronous, case-based questions that touched iteratively on Bloom’s cognitive taxonomy levels. The social pedagogy model’s wiki assignments were explored using abductive qualitative data analysis.

Results

Qualitative analysis revealed that learners acquired and applied a conceptual framework for approaching pharmacology as a discipline, and demonstrated adaptive mastery by evaluating and interacting competently with unfamiliar drug information. Learners and faculty acquired habits of self-directed assessment seeking and learner-centered coaching, respectively; specifically, the model taught learners to look outward to peers, faculty, and external sources of information for credible and constructive feedback, and that this feedback could be trusted as a basis to direct performance improvement. 82–94% of learners rated the social pedagogy-based curriculum valuable.

Conclusions

This social pedagogy model is agnostic with regard to pharmacology and type of health professional learner; therefore, we anticipate its benefits to be transferable to other disciplines.
Correction to: Profile of children referred to primary health care physiotherapy: a longitudinal observational study in Norway
Authors: Evensen Kari Anne I. , Sellæg Siw , Stræte Anne-Cath , Hansen Anne E. , Meisingset Ingebrigt
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
COVID-19 pandemic and violence: rising risks and decreasing urgent care-seeking for sexual assault and domestic violence survivors
Authors: Muldoon Katherine A. , Denize Kathryn M. , Talarico Robert , Fell Deshayne B. , Sobiesiak Agnes , Heimerl Melissa , Sampsel Kari
Published: February 2021

Background

There is little information on care-seeking patterns for sexual assault and domestic violence during the COVID-19 pandemic. The objective of this study was to examine the changes in emergency department (ED) admissions for sexual assault and domestic violence since the COVID-19 pandemic was declared.

Methods

Observational ED admissions data from The Ottawa Hospital were analyzed from March 4 to May 5 (62 days) in 2020 (COVID-19 period) and compared to the same period in 2018 (pre-COVID-19). Total and mean weekly admissions were calculated for all-cause ED admissions and for sexual and domestic violence cases. A Poisson regression (without offset term) was used to calculate the weekly case count ratio and 95% confidence intervals (CI) between the two time periods. Case characteristics were compared using chi-square tests, and percent differences were calculated.

Results

Compared to pre-COVID-19, total ED admissions dropped by 1111.22 cases per week (32.9% reduction), and the Sexual Assault and Domestic Violence Program cases dropped 4.66 cases per week. The weekly case count ratio for sexual assault cases was 0.47 (95% CI 0.79–0.27), equivalent of 53.49% reduction in cases, and 0.52 (95% CI 0.93–0.29), equivalent to a 48.45% reduction in physical assault cases. The characteristics of presenting cases were similar by age (median 25 years), sex (88.57% female), assault type (57.14% sexual assault, 48.57% physical assault), and location (31.43% patient’s home, 40.00% assailant’s home). There was a significant increase in psychological abuse (11.69% vs 28.57%) and assaults occurring outdoors (5.19% vs 22.86%).

Conclusion

This study found a decrease in ED admissions for sexual assault and domestic violence during COVID-19, despite societal conditions that elevate risk of violence. Trends in care-seeking and assault patterns will require ongoing monitoring to inform the provision of optimal support for individuals experiencing violence, particularly as countries begin to re-open or lock-down again.
Overexpression of SP1 restores autophagy to alleviate acute renal injury induced by ischemia-reperfusion through the miR-205/PTEN/Akt pathway
Authors: Huang Chong , Chen Yan , Lai Bin , Chen Yan-Xia , Xu Cheng-Yun , Liu Yuan-Fei
Published: February 2021

Background

Acute kidney injury (AKI) is a major kidney disease with poor clinical outcome. SP1, a well-known transcription factor, plays a critical role in AKI and subsequent kidney repair through the regulation of various cell biologic processes. However, the underlying mechanism of SP1 in these pathological processes remain largely unknown.

Methods

An in vitro HK-2 cells with anoxia-reoxygenation injury model (In vitro simulated ischemic injury disease) and an in vivo rat renal ischemia-reperfusion injury model were used in this study. The expression levels of SP1, miR-205 and PTEN were detected by RT-qPCR, and the protein expression levels of SP1, p62, PTEN, AKT, p-AKT, LC3II, LC3I and Beclin-1 were assayed by western blot. Cell proliferation was assessed by MTT assay, and the cell apoptosis was detected by flow cytometry. The secretions of IL-6 and TNF-α were detected by ELISA. The targeted relationship between miR-205 and PTEN was confirmed by dual luciferase report assay. The expression and positioning of LC-3 were observed by immunofluorescence staining. TUNEL staining was used to detect cell apoptosis and immunohistochemical analysis was used to evaluate the expression of SP1 in renal tissue after ischemia-reperfusion injury in rats.

Results

The expression of PTEN was upregulated while SP1 and miR-205 were downregulated in renal ischemia-reperfusion injury. Overexpression of SP1 protected renal tubule cell against injury induced by ischemia-reperfusion via miR-205/PTEN/Akt pathway mediated autophagy. Overexpression of SP1 attenuated renal ischemia-reperfusion injury in rats.

Conclusions

SP1 overexpression restored autophagy to alleviate acute renal injury induced by ischemia-reperfusion through the miR-205/PTEN/Akt pathway.
Anti‐bacterial and wound healing‐promoting effects of zinc ferrite nanoparticles
Authors: Haghniaz Reihaneh , Rabbani Atiya , Vajhadin Fereshteh , Khan Taous , Kousar Rozina , Khan Abdul Rehman , Montazerian Hossein , Iqbal Javed , Libanori Alberto , Kim Han-Jun , Wahid Fazli
Published: February 2021

Background

Increasing antibiotic resistance continues to focus on research into the discovery of novel antimicrobial agents. Due to its antimicrobial and wound healing-promoting activity, metal nanoparticles have attracted attention for dermatological applications. This study is designed to investigate the scope and bactericidal potential of zinc ferrite nanoparticles (ZnFe2O4NPs), and the mechanism of anti-bacterial action along with cytocompatibility, hemocompatibility, and wound healing properties.

Results

ZnFe2O4NPs were synthesized via a modified co-precipitation method. Structure, size, morphology, and elemental compositions of ZnFe2O4NPs were analyzed using X-ray diffraction pattern, Fourier transform infrared spectroscopy, and field emission scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy. In PrestoBlue and live/dead assays, ZnFe2O4NPs exhibited dose-dependent cytotoxic effects on human dermal fibroblasts. In addition, the hemocompatibility assay revealed that the NPs do not significantly rupture red blood cells up to a dose of 1000 µg/mL. Bacterial live/dead imaging and zone of inhibition analysis demonstrated that ZnFe2O4NPs showed dose-dependent bactericidal activities in various strains of Gram-negative and Gram-positive bacteria. Interestingly, NPs showed antimicrobial activity through multiple mechanisms, such as cell membrane damage, protein leakage, and reactive oxygen species generation, and were more effective against gram-positive bacteria. Furthermore, in vitro scratch assay revealed that ZnFe2O4NPs improved cell migration and proliferation of cells, with noticeable shrinkage of the artificial wound model.

Conclusions

This study indicated that ZnFe2O4NPs have the potential to be used as a future antimicrobial and wound healing drug.
Health care workers’ experiences of managing foetal distress and birth asphyxia at health facilities in Northern Uganda
Authors: Ayebare Elizabeth , Ndeezi Grace , Hjelmstedt Anna , Nankunda Jolly , Tumwine James K. , Hanson Claudia , Jonas Wibke
Published: February 2021

Background

Birth asphyxia is one of the leading causes of intrapartum stillbirth and neonatal mortality worldwide. We sought to explore the experiences of health care workers in managing foetal distress and birth asphyxia to gain an understanding of the challenges in a low-income setting.

Methods

We conducted in-depth interviews with 12 midwives and 4 doctors working in maternity units from different health facilities in Northern Uganda in 2018. We used a semi-structured interview guide which included questions related to; health care workers’ experiences of maternity care, care for foetal distress and birth asphyxia, views on possible preventive actions and perspectives of the community. Audio recorded interviews were transcribed verbatim and analysed using inductive content analysis.

Results

Four categories emerged: (i) Understanding of and actions for foetal distress and birth asphyxia including knowledge, misconception and interventions; (ii) Challenges of managing foetal distress and birth asphyxia such as complexities of the referral system, refusal of referral, lack of equipment, and human resource problems, (iii) Expectations and blame from the community, and finally (iv) Health care worker’ insights into prevention of foetal distress and birth asphyxia.

Conclusion

Health care workers described management of foetal distress and birth asphyxia as complex and challenging. Thus, guidelines to manage foetal distress and birth asphyxia that are specifically tailored to the different levels of health facilities to ensure high quality of care and reduction of need for referral are called for. Innovative ways to operationalise transportation for referral and community dialogues could lead to improved birth experiences and outcomes.