bluuebunny/crossref_metadata_2025 huggingface dataset:
What is Standard Dose of Rivaroxaban in Elderly Asian Patients with Atrial Fibrillation: 20ms versus. 15mg?
Authors: Kim Sung Soo , Lee Ki Hong , Yoon Nam Sik , Park Hyung Wook , Cho Jeong Gwan
Published: November 2021

Although there is no age criterion for rivaroxaban dose reduction, elderly patients with atrial fibrillation (AF) are often prescribed an off-label reduced dose. We aimed to evaluate whether age is a necessary criterion for rivaroxaban dose reduction in Korean patients with AF. Among 2208 patients who prescribed warfarin or rivaroxaban, 552 patients over 75 years without renal dysfunction (creatinine clearance >50 mL/min) were compared based on propensity score matching. The rivaroxaban group was further divided into a 20 mg (R20; on-label) and a 15 mg (R15; off-label). Primary net clinical benefit (NCB) was defined as the composite of stroke, systemic embolism, major bleeding, and all-cause mortality. Secondary NCB was defined as the composite of stroke, systemic embolism, and major bleeding. Patients were followed for 1 year, or until the first outcome occurrence. Both rivaroxaban groups had comparable efficacy compared with warfarin. However, both R20 (0.9% vs 7.4%, p = .014) and R15 (2.3% vs 7.4%, p = .018) had a significant reduction in major bleeding. There were no differences in efficacy or safety outcomes between R20 and R15. R20 had significantly reduced primary (hazard ratio [HR] 0.33, 95% confidence interval [CI]: 0.12–0.93) and secondary (HR 0.31, 95% CI: 0.10–0.93) NCBs compared with warfarin. However, primary and secondary NCBs were not reduced in R15. In real-world practice with elderly patients with AF, off-label rivaroxaban dose reduction to 15 mg conferred no benefits. Therefore, guideline-adherent rivaroxaban 20 mg is favorable in elderly Korean patients with AF.
Greater trochanteric pain syndrome: focused shockwave therapy versus an ultrasound guided injection: a randomised control trial
Authors: Heaver Catriona , Pinches Megan , Kuiper Jan Herman , Thomas Geraint , Lewthwaite Simon , Burston Ben J , Banerjee Robin D
Published: November 2021

Background:

Greater trochanteric pain syndrome (GTPS) is a common problem with an incidence of 1.8–5.6 per 1000 population. Physiotherapy, anti-inflammatories, corticosteroid injections and surgery have all been described in the management of GTPS, with limited, temporal success. Extracorporeal shockwave therapy (ESWT) has been proposed as a potential non-invasive management option for this difficult presentation.

Method:

We ran a prospective, 2-arm, single-blinded, randomised control trial comparing focused shockwave therapy (f-ESWT) to an ultrasound guided corticosteroid injection. Primary outcome measure was the visual analogue pain score. Secondary outcome measures included the Harris Hip Score (HHS) and Trendelenburg test for function; SF-36 for quality of life (QoL); and a Likert scale question for subjective assessment of symptom improvement.

Results:

104 patients (10 males and 94 females), of mean age 61.5 years were recruited. 53 were randomised to receive ESWT and 51 to receive an image-guided injection. 11 patients were lost to follow-up. There were no significant differences in baseline scores between groups. At 3 months, pain, function and QoL scores had improved in both groups but were not statistically significant. The Trendelenburg test was significantly improved in the f-ESWT group with 80% patients being negative compared to 20% at baseline ( p < 0.001). At 12 months, across all outcomes, the ESWT group had significantly improved scores compared to the injection group; VAS 37.1 versus 55.0 ( p = 0.007, 95% confidence interval [CI], 6.3–30.8), HHS 69.7 versus 57.5 ( p = 0.002, 95% CI, −20.0 to −4.6) and SF-36 52.4 versus 47.7 ( p = 0.048, 95% CI, −9.31 to −0.04). The improvement in Trendelenburg test was maintained in the ESWT group, but the injection group had reverted to baseline ( p < 0.001).

Conclusions:

We have shown f-ESWT is an effective treatment for patients with GTPS. We would advocate f-ESWT as an effective non-invasive treatment modality for this challenging patient population. Trial Registration No. ISRCTN8338223
Accuracy of chest radiography compared to ultrasound for positioning the umbilical venous catheter in neonates: A meta-analysis and systematic review
Authors: Cao Juan , Zhang Yuzheng , Yin Yanling , Liu Yuxiu
Published: November 2021

This study was aimed to investigate the accuracy of anteroposterior chest radiography for tip position verification for the umbilical venous catheters in neonates compared to ultrasound. A search in the PubMed, Embase, the Cochrane Library, and EBSCO was conducted to evaluate all the related articles on umbilical venous catheter (UVC), ultrasound AND neonates updated to August, 2020. Study selection, data extraction, and quality assessment were performed independently by two investigators. Random effects model was used to estimate the pooled sensitivity, specificity, and diagnostic odds ratio (DOR). The summary receiver operator characteristic (SROC) curve was constructed, and the area under the SROC curve (AUC) was calculated. Fourteen related studies were finally included for meta-analysis. The overall diagnostic sensitivity and speciﬁcity of X-ray on tip verification of UVC were 0.90 (95% CI 0.71–0.97) and 0.82 (95% CI 0.53–0.95), respectively. The pooled DOR was 3.69 (95% CI 1.64–5.71). The AUC was 0.93 (95% CI 0.90–0.95). The meta-regression analysis suggested that study sample size, study design, different US confirming method, and different gold standard in original design might be potential sources of heterogeneity. Our conclusion is that the commonly used anteroposterior X-ray is not reliable in identifying the exact anatomical location of UVC tip in neonates. Studies suggested ultrasound or echocardiography with saline contrast injection could be the gold standard for verification of catheter location and should be considered whenever possible, especially in premature patients. More studies are needed to expand the use of ultrasound or echocardiography in tip position confirming of UVCs.
Bringing research back home: exploring Indigenous Melanesian tok stori as ontology
Authors: Sanga Kabini , Reynolds Martyn
Published: November 2021

Indigenous knowledge is generally understood to be knowledge developed by a particular group in their specific environment over an extended period of time. In academia generally, bodies of knowledge of differing origins are not often understood. This article employs ontology as a ground for developing relational clarity in the academy by considering two oral traditions—talanoa (a Polynesian conversational form) as represented in research and Melanesian tok stori (a Melanesian form of discursive group communication) understood through an Indigenous Solomon Islands ontology. The discussion of tok stori offers a window into the complex ontological thinking required of the academy when seeking to learn from the knowledge of Mala’ita Solomon Islands specifically, and from Indigenous groups generally. The value to the wider research community suggests that bringing research back home through approaches constructed on the way people act can capitalise on the logic of aligning ontology and practice in research.
Volume/shear work ratio influence on wear and stress of soil chisel tine modelled by DEM
Authors: Katinas Egidijus , Choteborsky Rostilav
Published: November 2021

Agricultural equipment is working in very high-stress conditions. However, it has a significant influence on the wear losses of soil processing parts. Chisel is operating at 30 cm working depth at a maximum of 12 km·h−1 working speed. Due to unpredictable soil conditions, chisel tines suffer high wear losses. It leads to time consumption and cost expenses during the soil preparation period. Wear resistance, and agronomical requirements (working depth, loosening of soil) are the main criteria of agricultural equipment producers. The discrete element method is a solution that simulates soil as sphere shape particles with soil properties. Wear results reveal the change of parts shape, acting forces, and stresses during the simulation in the virtual soil bin. The used Rocky DEM software uses a parameter C (volume/shear work ratio) to describe wear intensity, which varies for different geometry. Chisel tine geometry should be divided into sections with varied parameter C according to stress acting on the surface. The test conditions can be used for future wear analysis of varied tool geometry and protection (sintered tungsten carbide plates, hard-faced surface, etc.) agricultural tools to compare its durability in different soil conditions.
Comparison of three galenic forms of lamivudine in young West African children living with Human Immunodeficiency Virus
Authors: Pressiat Claire , Dainguy Evelyne , Tréluyer Jean-Marc , Yonaba Caroline , Urien Saik , Eboua François , Foissac Frantz , Dahourou Désiré Lucien , Bouazza Naïm , Malateste Karen , Desmonde Sophie , Pruvost Alain , Leroy Valériane , Hirt Déborah , Study Group The MONOD ANRS
Published: November 2021

Background

Few pharmacokinetic data were reported on dispersible tablets despite their increasing use. One hundred fifty HIV-infected children receiving lamivudine were enrolled in the MONOD ANRS 12,206 trial. Three galenic forms were administered: liquid formulation, tablet form and dispersible scored tablet.

Method

HIV-infected children <4 years old were enrolled in the MONOD ANRS 12,206 trial designed to assess the simplification of a successful 12-months lopinavir-based antiretroviral treatment with efavirenz. Lamivudine plasma concentrations were analysed using nonlinear mixed effects modelling approach.

Results

One hundred and fifty children (age: 2.5 years (1.9–3.2), weight 11.1 (9.5–12.5) kg (median (IQR)) were included in this study. Over the study period, 79 received only the syrup form, 29 children switched from syrup form to tablet 3TC/AZT form, 36 from syrup to the orodispersible ABC/3TC form and two from the 3TC/AZT form to the orodispersible ABC/3TC form. The 630 lamivudine concentrations were best described by a two-compartment model allometrically scaled. Galenic form had no significant effect on 3TC pharmacokinetic.

Conclusion

This trial provided an opportunity to compare three galenic forms (liquid formulation, tablet form and dispersible scored tablet) of lamivudine in the target population of young HIV–1-infected children. Galenic form had no significant effect on lamivudine pharmacokinetics.
Influence of recent direct-to-EVT trials on practical decision-making for the treatment of acute ischemic stroke patients
Authors: McDonough Rosalie , Ospel Johanna , Kashani Nima , Kappelhof Manon , Liu Jianmin , Yang Pengfei , Majoie Charles , Roos Yvo , Goyal Mayank
Published: November 2021

Background

Current guidelines recommend that eligible acute ischemic stroke (AIS) patients receive intravenous alteplase (IVT) prior to endovascular treatment (EVT). Six randomized controlled trials recently sought to determine the risks of administering IVT prior to EVT, five of which have been published/presented. It is unclear whether and how the results of these trials will change guidelines. With the DEBATE survey, we assessed the influence of the recent trials on physicians’ IVT treatment strategies in the setting of EVT for large vessel occlusion (LVO) stroke.

Methods

Participants were provided with 15 direct-to-mothership case-scenarios of LVO stroke patients and asked whether they would treat with IVT  +  EVT or EVT alone, a) before publication/presentation of the direct-to-EVT trials, and b) now (knowing the trial results). Logistic regression clustered by respondent was performed to assess factors influencing the decision to adopt an EVT-alone paradigm after publication/presentation of the trial results.

Results

289 participants from 37 countries provided 4335 responses, of which 13.5% (584/4335) changed from an IVT  +  EVT strategy to EVT alone after knowing the trial results. Very few switched from EVT alone to IVT  +  EVT (8/4335, 0.18%). Scenarios involving a long thrombus (RR 1.88, 95%CI:1.56–2.26), cerebral micro-hemorrhages (RR 1.78, 95%CI:1.43–2.23), and an expected short time to recanalization (RR 1.46 95%CI:1.19–1.78) had the highest chance of participants switching to an EVT-only strategy.

Conclusion

In light of the recent direct-to-EVT trials, a sizeable proportion of stroke physicians appears to be rethinking IVT treatment strategies of EVT-eligible mothership patients with AIS due to LVO in specific situations.
Experiences of living with postural tachycardia syndrome
Authors: Waterman Samantha , Opie Morwenna , Waterman Debbie , Langdon Dawn
Published: November 2021

Objective

Postural tachycardia syndrome (PoTS) is a disorder of the autonomic nervous system which involves a range of symptoms, worsened when adopting an orthostatic (upright) position. Symptoms can include tachycardia, dizziness, fainting, nausea as well as many others which, as is typical of a syndrome, vary from person to person. Although research is increasing into this condition, the unifying experiences of managing it on a daily basis have not been extensively investigated. This study aimed to capture participants’ experiences of living with PoTS.

Method

A longitudinal digital ethnographic approach was employed. Eight participants recorded daily video diaries discussing their experiences of PoTS and its impact for 17 days. Interpretative phenomenological analysis was utilised to analyse the data and identify connections across participants’ accounts.

Results

Four superordinate themes emerged: ‘loss of control and lack of agency over body’, ‘identity changes’, ‘lack of understanding from others’ and ‘adapting to cope with PoTS’.

Discussion

The findings demonstrated the complex and widespread impact these participants experience from their PoTS symptoms, including the consequent emotional difficulties that result from managing this condition. An overall lack of understanding about PoTS by others was emphasised, suggesting the requirement for better education and support services for this condition.
Management of surgical patients on opioid replacement therapy: An audit of current practice
Authors: Mayfield Karla , White Leigh , Nolan Timothy , Conner Xavier , Dittmer Brendan , ABI-Fares Catherine , Mitchell Andrew
Published: November 2021

Patients on opioid replacement therapy hospitalised with acute pain represent a clinical challenge and have poorer perioperative outcomes. There is limited evidence relating to acute pain management of this complex cohort. The primary objectives of this retrospective audit was to establish the number of patients who are admitted on opioid replacement therapy with an acute pain condition under surgical services and evaluate the management of these patients to determine consistency of pain management practices. Secondarily, we aimed to evaluate the documentation of opioid replacement therapy in clinical notes to determine adherence to operational protocols and record clinically relevant outcomes including infection or postoperative complication rates. Forty-four episodes of care for buprenorphine patients and 19 episodes of care for methadone patients were included. There was significant variability in inpatient opioid prescribing, including practice of dose modification, and there was high utilisation of additional opioids, although agent choice varied. Multimodal analgesia was utilised, especially following acute pain service review. There was an 11% readmission rate for complications of the initial presentation. Documentation at transitions of care was poor. There is a need for further clinical studies into specific acute pain management strategies, and their effect on clinically relevant outcomes, to guide consistent management practices.
Circulating innate lymphoid cell subtypes and altered cytokine profiles following an atherogenic high-fat diet
Authors: Mxinwa Vuyolwethu , Dludla Phiwayinkosi V. , Nyambuya Tawanda M. , Nkambule Bongani B.
Published: November 2021

Impaired Glc tolerance and hyperinsulinemia are a hallmark of type 2 diabetes (T2D) and are associated with an altered innate and adaptive immune response. In this study, we used a high-fat diet (HFD)-induced model of pre-diabetes to explore the pathological implications of altered innate lymphoid cell (ILC) profiles in a state of impaired Glc tolerance. Sixteen male C57BL/6 mice were randomized to receive two experimental diets ( n = 8 per group), low-fat (LFD), and HFD for 8–13 wk. We evaluated the levels of circulating innate lymphoid cells and their respective cytokines following HFD-feeding. The HFD group had impaired Glc tolerance, elevated insulin levels, and increased total cholesterol levels. Notably, the levels of circulating ILC1s were elevated following 13 wk of HFD-feeding. Moreover, the levels of TNF-α were decreased, but there were no changes in IFN-γ levels. Lastly, the levels of circulating ILC2s and ILC3s were comparable between the HFD and LFD group. The findings demonstrated that short-term HFD-feeding increases postprandial blood Glc, total cholesterol and insulin levels. However, the metabolic changes did not alter ILC2 and ILC3 levels and their respective cytokine profiles.
Legal challenges in bringing AI evidence to the criminal courtroom
Authors: Quezada-Tavárez Katherine , Vogiatzoglou Plixavra , Royer Sofie
Published: November 2021

Artificial Intelligence (AI) is rapidly transforming the criminal justice system. One of the promising applications of AI in this field is the gathering and processing of evidence to investigate and prosecute crime. Despite its great potential, AI evidence also generates novel challenges to the requirements in the European criminal law landscape. This study aims to contribute to the burgeoning body of work on AI in criminal justice, elaborating upon an issue that has not received sufficient attention: the challenges triggered by AI evidence in criminal proceedings. The analysis is based on the norms and standards for evidence and fair trial, which are fleshed out in a large amount of European case law. Through the lens of AI evidence, this contribution aims to reflect on these issues and offer new perspectives, providing recommendations that would help address the identified concerns and ensure that the fair trial standards are effectively respected in the criminal courtroom.
Utilization of a 3-D tissue engineered model to investigate the effects of perfusion on gynecologic cancer biology
Authors: Martinez Alba , Buckley Molly S , Scalise Carly B , Wang Dezhi , Katre Ashwini A , Birrer Michael J , Berry Joel L , Arend Rebecca C
Published: November 2021

Among gynecologic malignancies, ovarian cancer (OC) has the poorest survival rate, and its clinical management remains challenging due to the high rate of recurrence and chemoresistance. Improving survival for these patients is critical, although this requires the ability to translate preclinical studies to actual patient care: bench to bedside and back. Our objective was to develop a preclinical model that accurately represents tumor biology and its microenvironment. We utilized SKOV-3, OVCAR-8, and CS-99 cell lines to show that this model was suitable for in vitro assessment of cell proliferation. We tested OC cells independently and in co-culture with cancer associated fibroblasts (CAFs) or immune cells. Additionally, we used patient-derived ovarian carcinoma and carcinosarcoma samples to show that the system maintains the histologic morphology of the primary tissue after 7 days. Moreover, we tested the response to chemotherapy using both cell lines and patient-derived tumor specimens and confirmed that cell death was significantly higher in the treated group compared to the vehicle group. Finally, we immune profiled the 3-D model containing patient tissue after several days in the bioreactor system and revealed that the immune populations are still present. Our data suggest that this model is a suitable preclinical model to aid in research that will ultimately impact the treatment of patients with gynecologic cancer.
Does Worrying Matter? Priming and Attitudes Toward Mask Wearing in a Midwestern State
Authors: Huang Francis L. , Reinke Wendy , Herman Keith
Published: November 2021

Due to the spread of the coronavirus disease 2019 (COVID-19), the use of protective measures (e.g., mask wearing and social distancing) has become an important public health concern. Despite being an effective and low-cost measure, mask wearing in the U.S. is a contentious issue. We investigated data coming from a natural experiment ( n = 1,993) collected in a Midwestern state where survey questions about mask wearing and COVID-19 were presented in a random order. Primed respondents ( n = 1,011), who answered COVID-19 related questions prior to the mask questions, indicated no differences in the efficacy of masks in stopping the spread of the virus compared to nonprimed respondents ( n = 982). However, primed respondents who were not worried about getting sick were 37% less likely to believe in the efficacy of masks compared the nonprimed, nonworried respondents. Nonworried respondents represent a high-risk group who are likely not to wear a mask. Implications for the messages used in public health campaigns to elicit a change in behaviors are discussed.
Addressing the Long COVID Crisis: Integrative Health and Long COVID
Authors: Roth Alan , Chan Pan San , Jonas Wayne
Published: November 2021

While COVID-19 has killed millions of people globally, its lasting effects on the health and well-being of entire populations are just becoming clear. As many as 30% of those diagnosed with COVID-19 report continuing health-related problems, regardless of the severity of the initial infection. Given the infection rate in the world, that translates to between 5.4 and 17.9 million globally; about 700 000 in the US. The syndrome goes by many names; here we call it “long COVID.” Patients experience a wide range of symptoms, including serious organ system effects such as pulmonary fibrosis, myocarditis, new diabetes diagnoses, stroke, and other cerebrovascular events. They also experience ongoing pain, fatigue, and cognitive dysfunction. We suggest here that these patients require an integrative health approach, one that combines traditional medical management, non-pharmacological approaches, and behavior and lifestyle changes. Such an approach has been shown to be beneficial in other chronic illnesses such as fibromyalgia, chronic fatigue syndrome, and post-Lyme disease.
Better immediate and early postoperative outcomes of unicompartmental knee replacement comparing with total knee replacement: A matched cohort of patients with medial knee osteoarthritis
Authors: Yu Hiu-Kiu , Tang Bruce Yan-Ho , Wong Hok-Leung , Sasaki Sumire , Wong Tai-Fong
Published: November 2021

Introduction: This study compared the immediate and early postoperative outcomes of medial compartment knee osteoarthritis patients receiving unicompartmental knee replacement (UKR) with a matched cohort of total knee replacement (TKR). Methods: 26 UKR patients were matched with 26 TKR patients based on age, body mass index, pre-operative radiographic severity, range of motion (ROM), Knee Society score (KSS) and Feller patella score. Immediate postoperative outcomes were reflected by postoperative pain, blood loss, length of stay and the number of physiotherapy sessions attended. Early postoperative outcomes (ROM and KSS) were measured at 3 months and 1 year post-operatively. Results: UKR patients had less hemoglobin drop (UKR: 1.2 g/dL, TKR: 1.6 g/dL, p = 0.04), shorter length of stay (UKR: 4.3 days, TKR: 6.0 days, p < 0.001) and required less physiotherapy sessions for recovery (UKR: 6.9 sessions, TKR: 9.3 sessions, p < 0.05). There were no statistically significant differences in early post-operative pain score and postoperative analgesia use ( p > 0.05) between the two groups. Patients receiving UKR had significantly higher post-operative KSS (UKR: 155.9, TKR: 142.4, p = 0.005) and ROM (UKR: 115.8o, TKR: 98.8o, p < 0.001) at 3 months. The KSS and ROM of UKR group at 3 months was better than TKR group at 1-year follow-up. Conclusion: In patients with medial knee osteoarthritis, UKR showed less postoperative analgesic use and blood loss, shorter length of stay, shorter course of rehabilitation and faster recovery with better early KSS and ROM than TKR. Follow up is necessary for comparison in long term outcome and survivorship between the two groups.
Higher Clinician-Patient Communication Is Associated With Greater Satisfaction With HIV Care
Authors: Wachira Juddy , Mwangi Ann , Chemutai Diana , Nyambura Monica , Genberg Becky , Wilson Ira B.
Published: November 2021

Provider-patient communication (PPC) skills are key in promoting patient satisfaction. Our study examined the relationship between clinician PPC skills and patient satisfaction with care among virally unsuppressed adult HIV patients in Busia County, Kenya. This cross-sectional study was conducted among 360 HIV patients on first line antiretroviral regimen and having a recent viral load ≥400 copies HIV RNA/ml. We conducted logistic regression analysis. The mean age of participants was 48.2 years [standard deviation (SD): 12.05]. Overall, the mean score on clinician PPC skills was 33.3 (SD: 9.0). A high proportion (85%) of participants reported satisfaction with the HIV care services. After adjusting for covariates, the odds of being satisfied with care increased by 19% (adjusted odds ratio: 1.19, 95% CI: 1.11-1.30) for every one unit increase in the clinician PPC skills score. Promoting good PPC skills may be key to improving patient satisfaction with HIV care.
Book review: Peggy Mohan, Wanderers, Kings, Merchants: The Story of India Through Its Languages
Authors: Habib Irfan
Published: November 2021

Peggy Mohan, Wanderers, Kings, Merchants: The Story of India Through Its Languages (Gurgaon: Penguin/Viking), 2021, 341 + xvii pp., ₹599 (hb).
The protein-protein interaction ontology: for better representing and capturing the biological context of protein interaction
Authors: Li Mansheng , He Qiang , Yang Chunyuan , Ma Jie , He Fuchu , Chen Tao , Zhu Yunping
Published: November 2021

Background

With the rapid increase in the amount of Protein-Protein Interaction (PPI) data, the establishment of an event-centered PPI ontology that contains temporal and spatial vocabularies is urgently needed to clarify PPI biological annotations. In this paper, we propose a precisely designed schema - PPIO (PPI Ontology) for representing the biological context of PPIs.

Results

Inspired by the event model and the distinct characteristics of PPI events, PPIO consists of six core aspects of the information required for reporting a PPI event, including the interactor (who), the biological process (when), the subcellular location (where), the interaction type (how), the biological function (what) and the detection method (which). PPIO is implemented through the integration of appropriate terms from the corresponding vocabularies/ontologies, e.g., Gene Ontology, Protein Ontology, PSI-MI/MOD, etc. To assess PPIO, an approach based on PPIO in developed to extract PPI biological annotations from an open standard corpus “BioCreAtIvE-PPI”. The experiment results demonstrate PPIO’s high performance, a precision of 0.69, a recall of 0.72 and an F-score of 0.70.

Conclusions

PPIO is a well-constructed essential ontology in the interpretation of PPI biological context. The results of the experiments conducted on the BioCreAtIvE corpus demonstrate that PPIO is able to facilitate PPI annotation extraction from biomedical literature effectively and enrich essential annotation for PPIs.
Usefulness of ECG criteria to rule out left ventricular hypertrophy in older individuals with true left bundle branch block: an observational study
Authors: Tavares Caio Assis Moura , Samesima Nelson , Lazar Neto Felippe , Hajjar Ludhmila Abrahão , Godoy Lucas C. , Padrão Eduardo Messias Hirano , Facin Mirella , Jacob Filho Wilson , Farkouh Michael E. , Pastore Carlos Alberto
Published: November 2021

Background

Advanced age is associated with both left bundle branch block (LBBB) and hypertension and the usefulness of ECG criteria to detect left ventricular hypertrophy (LVH) in patients with LBBB is still unclear. The diagnostic performance and clinical applicability of ECG-based LVH criteria in patients with LBBB defined by stricter ECG criteria is unknown. The aim of this study was to compare diagnostic accuracy and clinical utility of ECG criteria in patients with advanced age and strict LBBB criteria.

Methods

Retrospective single-center study conducted from Jan/2017 to Mar/2018. Patients undergoing both ECG and echocardiogram examinations were included. Ten criteria for ECG-based LVH were compared using LVH defined by the echocardiogram as the gold standard. Sensitivity, specificity, predictive values, likelihood ratios, AUC, and the Brier score were used to compare diagnostic performance and a decision curve analysis was performed.

Results

From 4621 screened patients, 68 were included, median age was 78.4 years, (IQR 73.3–83.4), 73.5% with hypertension. All ECG criteria failed to provide accurate discrimination of LVH with AUC range between 0.54 and 0.67, and no ECG criteria had a balanced tradeoff between sensitivity and specificity. No ECG criteria consistently improved the net benefit compared to the strategy of performing routine echocardiogram in all patients in the decision curve analysis within the 10–60% probability threshold range.

Conclusion

ECG-based criteria for LVH in patients with advanced age and true LBBB lack diagnostic accuracy or clinical usefulness and should not be routinely assessed.
The timing of administering aspirin and nitroglycerin in patients with STEMI ECG changes alter patient outcome
Authors: Todoroski Kristijan B.
Published: November 2021

Background

Both chewed aspirin and sublingual nitroglycerin are fast acting medications and reach therapeutic levels within a few minutes. Current guidelines for managing acute coronary syndrome (ACS) do not recognize the importance of the order or timing of administering aspirin and nitroglycerin. This retrospective study aimed to examine if there was any benefit to the timing of giving aspirin before or after nitroglycerin in cases of ACS.

Methods

From the large National Emergency Medical Services Information System (NEMSIS) 2017 Version database, 2594 patients with acute coronary syndrome were identified (based on chest pain and their ECG finding) that received aspirin plus nitroglycerin in prehospital settings. Based on which medication was given first, the patients were separated in 2 groups: an aspirin-first and a nitroglycerin-first group. The 2246 patients who received aspirin first were further stratified based on the time between administration of aspirin and the first dose of nitroglycerin. The other 348 patients who received nitroglycerin first were similarly stratified.

Results

In patients with STEMI ischemia, giving nitroglycerin 10 min after aspirin dosing (compared to giving them simultaneously) leads to a greater than 20% reduction in need for additional nitroglycerin, a greater than 7% decrease in subjective pain experienced by the patient and reduced need for additional opioids. The aspirin-first group in total, had a 39.6% decrease in subjective pain experience after giving additional nitroglycerin compared to nitroglycerin-first group.

Conclusion

In patients with ACS, this study found that giving nitroglycerin 10 min after aspirin was associated with a reduction in subjective pain scores, as well as a reduced need for additional nitroglycerin or opioids. Future prospective trials examining the timing of aspirin vs. nitroglycerin are needed to confirm these findings.
Undertaking general practice quality improvement to improve cancer screening - a thematic analysis of provider experiences
Authors: Trankle Steven A. , Metusela Christine , Reath Jennifer
Published: November 2021

Background

Cancer is a major cause of illness and death, and its incidence and mortality can be reduced through effective screening. In order to improve below target screening rates in one region of Australia, the local Primary Health Network supported local general practices to implement a range of quality improvement initiatives.

Methods

We used a qualitative approach and interviewed 18 general practice staff and five Primary Health Network staff and contractors to understand their experiences with these quality improvement initiatives.

Results

In a thematic analysis, we identified four key themes related to program set-up and implementation; patient and community education and promotion; engaging patients and communities in screening; and general practice enhancement. Program roles were clear and understood, and the program received strong oversight and support. Practice staff felt supported and motivated. Information Technology was a challenge for many practices often requiring tailored assistance. Education provided by practices facilitated patient empowerment but practice staff noted difficulties engaging patients in screening. Practices were enhanced though strong leadership and teamwork and practice learning activities.

Conclusions

The tailored evidence-based quality improvement initiatives were considered effective in supporting general practices to increase their cancer screening. Key facilitators reported by participants included use of Plan-Do-Study-Act cycles, enhanced data entry and audit capacity, effective recall and reminder systems and maintaining staff motivation.
Soluble urokinase plasminogen activator receptor is associated with short-term mortality and enhanced reactive oxygen species production in acute-on-chronic liver failure
Authors: Wang Yunyun , Wu Fengtian , Chen Chao , Xu Lichen , Lin Wei , Huang Chunhong , Yang Ying , Wu Shanshan , Qi Jinjin , Cao Hanqin , Li Guojun , Hong Meng , Zhu Haihong
Published: November 2021

Background

Acute-on-chronic liver failure (ACLF) is a comprehensive syndrome characterized by an acute deterioration of liver function and high short-term mortality rates in patients with chronic liver disease. Whether plasma soluble urokinase plasminogen activator receptor (suPAR) is a suitable biomarker for the prognosis of patients with ACLF remains unknown.

Method

A prospective cohort of 282 patients with ACLF from three hospitals in China was included. 88.4% of the group was hepatitis B virus-related ACLF (HBV-related ACLF). Cox regression was used to assess the impact of plasma suPAR and other factors on 30- and 90-day mortality. Reactive oxygen species (ROS) production were detected to explore the role of suPAR in regulating neutrophil function in HBV-related ACLF.

Result

There was no difference in plasma suPAR levels between HBV-related and non-HBV-related ACLF. Patients with clinical complications had higher suPAR levels than those without these complications. A significant correlation was also found between suPAR and prognostic scores, infection indicators and inflammatory cytokines. Cox’s regression multivariate analysis identified suPAR ≥ 14.7 ng/mL as a predictor for both day 30 and 90 mortality (Area under the ROC curve: 0.751 and 0.742 respectively), independent of the MELD and SOFA scores in patients with ACLF. Moreover, we firstly discovered suPAR enhanced neutrophil ROS production under E.coli stimulation in patients with HBV-related ACLF.

Conclusions

suPAR was a useful independent biomarker of short-term outcomes in patients with ACLF and might play a key role in the pathogenesis.

Trial registration CNT, NCT02965560.
Two extraction-free reverse transcription loop-mediated isothermal amplification assays for detection of SARS-CoV-2
Authors: Lai Meng Yee , Bukhari Fatma Diyana Mohd , Zulkefli Nur Zulaikha , Ismail Ilyiana , Mustapa Nur Izati , Soh Tuan Suhaila Tuan , Hassan Afifah Haji , Peariasamy Kalaiarasu M. , Lee Yee Leng , Suppiah Jeyanthi , Thayan Ravindran , Lau Yee Ling
Published: November 2021

Background

Current assays for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rely on time consuming, costly and laboratory based methods for virus isolation, purification and removing inhibitors. To address this limitation, we propose a simple method for testing RNA from nasopharyngeal swab samples that bypasses the RNA purification step.

Methods

In the current project, we have described two extraction-free reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays for the detection of SARS-CoV-2 by using E gene and RdRp gene as the targets.

Results

Here, results showed that reverse transcription loop-mediated isothermal amplification assays with 88.4% sensitive (95% CI: 74.9–96.1%) and 67.4% sensitive (95% CI: 51.5–80.9%) for E gene and RdRp gene, respectively.

Conclusion

Without the need of RNA purification, our developed RT-LAMP assays for direct detection of SARS-CoV-2 from nasopharyngeal swab samples could be turned into alternatives to qRT-PCR for rapid screening.
Comprehensive analysis of lymph nodes metastasis associated genes in cervical cancer and its significance in treatment and prognosis
Authors: Yang Ping , Ruan Youqin , Yan Zhiling , Gao Yang , Yang Hongying , Wang Shaojia
Published: November 2021

Background

Cervical carcinoma is one of the most common malignant tumors of the female reproductive system. Lymph nodes metastasis, the most common metastasis, which can be detected even in small-size tumor patients, results in worse prognosis. Therefore, it is of great significance to explore novel lymph nodes metastasis associated biomarkers, which can predict the prognosis and provide a good reference for clinical decision making in cervical carcinoma patients. However, systematic and comprehensive studies related to the key molecules in lymph node metastasis in cervical carcinoma patients are still absent.

Methods

Transcriptome and clinical data of 307 cervical carcinoma patients were obtained from The Cancer Genome Atlas (TCGA). Then, survival of patients with and without lymph node metastasis was analyzed by Kaplan-Meier (K-M) curves. Differential expressed genes (DEGs) were detected between tumor and control samples using limma package and defined as lymph node metastasis related genes. Univariate and multivariate Cox regression analyses were carried out to screen robust prognostic gene signature. The risk score model and nomogram for predicting survival were constructed based on prognostic gene signature. The performance of the risk score model was evaluated by operating characteristic (ROC) curves. Based on risk score, patients were divided into low- and high- risk groups. DEGs, functional enrichment analysis and tumor microenvironment (immune infiltration and expressions of immune checkpoints) were detected in low- and high-risk groups.

Results

A total of 103 lymph node metastasis-associated genes were identified. Univariate and multivariate Cox regression analyses identified TEKT2, LPIN2, FABP4 and CXCL2 as prognostic gene signature. The risk score model was constructed and validated in cervical carcinoma patients. 345 DEGs identified between high- and low-risk groups were significantly enriched into immune-related biological processes. Furthermore, we found that the immune infiltration and expressions of immune checkpoints were significantly different between low- and high-risk groups.

Conclusion

Our study revealed that lymph node metastasis played an important role in the prognosis of cervical carcinoma patients. Furthermore, we established a risk score model based on lymph node metastasis related genes, which could accurately predict the survival of cervical carcinoma patients. Besides, our findings in tumor microenvironments of low- and high-risk groups improved our understanding of the relationship between lymph node metastasis related genes and cervical carcinoma.
The landscape of coding RNA editing events in pediatric cancer
Authors: Wen Ji , Rusch Michael , Brady Samuel W. , Shao Ying , Edmonson Michael N. , Shaw Timothy I. , Powers Brent B. , Tian Liqing , Easton John , Mullighan Charles G. , Gruber Tanja , Ellison David , Zhang Jinghui
Published: November 2021

Background

RNA editing leads to post-transcriptional variation in protein sequences and has important biological implications. We sought to elucidate the landscape of RNA editing events across pediatric cancers.

Methods

Using RNA-Seq data mapped by a pipeline designed to minimize mapping ambiguity, we investigated RNA editing in 711 pediatric cancers from the St. Jude/Washington University Pediatric Cancer Genome Project focusing on coding variants which can potentially increase protein sequence diversity. We combined de novo detection using paired tumor DNA-RNA data with analysis of known RNA editing sites.

Results

We identified 722 unique RNA editing sites in coding regions across pediatric cancers, 70% of which were nonsynonymous recoding variants. Nearly all editing sites represented the canonical A-to-I (n = 706) or C-to-U sites (n = 14). RNA editing was enriched in brain tumors compared to other cancers, including editing of glutamate receptors and ion channels involved in neurotransmitter signaling. RNA editing profiles of each pediatric cancer subtype resembled those of the corresponding normal tissue profiled by the Genotype-Tissue Expression (GTEx) project.

Conclusions

In this first comprehensive analysis of RNA editing events in pediatric cancer, we found that the RNA editing profile of each cancer subtype is similar to its normal tissue of origin. Tumor-specific RNA editing events were not identified indicating that successful immunotherapeutic targeting of RNA-edited peptides in pediatric cancer should rely on increased antigen presentation on tumor cells compared to normal but not on tumor-specific RNA editing per se.
A novel PDX modeling strategy and its application in metabolomics study for malignant pleural mesothelioma
Authors: Chen Zhongjian , Yang Chenxi , Guo Zhenying , Song Siyu , Gao Yun , Wang Ding , Mao Weimin , Liu Junping
Published: November 2021

Background

Malignant pleural mesothelioma (MPM) is a rare and aggressive carcinoma located in pleural cavity. Due to lack of effective diagnostic biomarkers and therapeutic targets in MPM, the prognosis is extremely poor. Because of difficulties in sample extraction, and the high rate of misdiagnosis, MPM is rarely studied. Therefore, novel modeling methodology is crucially needed to facilitate MPM research.

Methods

A novel patient-derived xenograft (PDX) modeling strategy was designed, which included preliminary screening of patients with pleural thickening using computerized tomography (CT) scan, further reviewing history of disease and imaging by a senior sonographer as well as histopathological analysis by a senior pathologist, and PDX model construction using ultrasound-guided pleural biopsy from MPM patients. Gas chromatography-mass spectrometry-based metabolomics was further utilized for investigating circulating metabolic features of the PDX models. Univariate and multivariate analysis, and pathway analysis were performed to explore the differential metabolites, enriched metabolism pathways and potential metabolic targets.

Results

After screening using our strategy, 5 out of 116 patients were confirmed to be MPM, and their specimens were used for modeling. Two PDX models were established successfully. Metabolomics analysis revealed significant metabolic shifts in PDX models, such as dysregulations in amino acid metabolism, TCA cycle and glycolysis, and nucleotide metabolism.

Conclusions

To sum up, we suggested a novel modeling strategy that may facilitate specimen availability for MM research, and by applying metabolomics in this model, several metabolic features were identified, whereas future studies with large sample size are needed.
Why parents agree or disagree for minimally invasive tissue sampling (MITS) to identify causes of death in under-five children and stillbirth in North India: a qualitative study
Authors: Das Manoja Kumar , Arora Narendra Kumar , Debata Pradeep , Chellani Harish , Rasaily Reeta , Gaikwad Harsha , Meena K. R. , Kaur Gurkirat , Malik Prikanksha , Joshi Shipra , Kumari Mahisha
Published: November 2021

Background

Information on exact causes of death and stillbirth are limited in low and middle income countries. Minimally invasive tissue sampling (MITS) is increasingly practiced in place of autopsy across several settings. A formative research documented the experiences of counselling and consenting for MITS in north India.

Methods

This exploratory qualitative study was conducted at a tertiary care hospital in Delhi. During the early implementation of MITS, observations of the counselling and consenting process (n = 13) for under-five child death and stillbirths were conducted. In-depth interviews with MITS team members (n = 3) were also conducted. Observation and interview data were transcribed and inductively analysed using thematic content analysis to identify emerging themes and codes.

Results

The MITS team participated in daily ward rounds for familiarisation with parents/families. Following death declaration the counselling was done in counselling corner of the ward or adjacent corridor. Mostly the counselling was targeted at the father and family members present, using verbal explanation and the consent document in local language. The key concerns raised by parents/family were possible disfigurement, time needed and possible benefits. Most of the parents consulted family members before consent. Among those who consented, desire for next pregnancy, previous pregnancy or neonatal loss and participation of treating senior doctor were the key factors. The negative experience of hospital care, poor comprehension and distance from residence were the factors for consent refusal. Lesser number of parents of deceased children consented for MITS compared to the neonates and stillbirths.

Conclusions

The initial experiences of obtaining consent for MITS were encouraging. Consent for MITS may be improved with active involvement of the treating doctors and nurses, better bereavement support, private counselling area along with improvement in quality of care and communication during hospitalisation. Special efforts and refinement in counselling are needed to improve consent for MITS in older children.