bluuebunny/crossref_metadata_2025 huggingface dataset:
Compound FC-10696 Inhibits Egress of Marburg Virus
Authors: Han Ziying , Ye Hong , Liang Jingjing , Shepley-McTaggart Ariel , Wrobel Jay E. , Reitz Allen B. , Whigham Alison , Kavelish Katrina N. , Saporito Michael S. , Freedman Bruce D. , Shtanko Olena , Harty Ronald N.
Published: April 2021

Marburg virus (MARV) VP40 protein (mVP40) directs egress and spread of MARV, in part, by recruiting specific host WW domain-containing proteins via its conserved PPxY late (L) domain motif to facilitate efficient virus-cell separation. We reported previously that small-molecule compounds targeting the viral PPxY/host WW domain interaction inhibited VP40-mediated egress and spread.
The Diadenylate Cyclase CdaA Is Critical for Borrelia turicatae Virulence and Physiology
Authors: Jackson-Litteken Clay D. , Ratliff C. Tyler , Kneubehl Alexander R. , Siletti Cheta , Pack Lindsay , Lan Renny , Huynh TuAnh N. , Lopez Job E. , Blevins Jon S.
Published: April 2021

Relapsingfever (RF), caused by spirochetes of the genusBorrelia, is a globally distributed, vector-borne disease with high prevalence in developing countries. To date, signaling pathways required for infection and virulence of RFBorreliaspirochetes are unknown.Cyclicdi-AMP(c-di-AMP), synthesized bydiadenylatecyclases (DACs), is a second messenger predominantly found in Gram-positive organisms that is linked to virulence and essential physiological processes.
The Expression and Nuclear Retention Element of Polyadenylated Nuclear RNA Is Not Required for Productive Lytic Replication of Kaposi’s Sarcoma-Associated Herpesvirus
Authors: Gutierrez Isaura Vanessa , Dayton Jacob , Harger Shannon , Rossetto Cyprian C.
Published: April 2021

KSHV is an oncogenic herpesvirus that establishes latency and exhibits episodes of reactivation. KSHV disease pathologies are most often associated with the lytic replication of the virus.
Enhancement of Antibody-Dependent Cellular Cytotoxicity and Phagocytosis in Anti-HIV-1 Human-Bovine Chimeric Broadly Neutralizing Antibodies
Authors: Edwards Jack M. , Heydarchi Behnaz , Khoury Georges , Salazar-Quiroz Natalia A. , Gonelli Christopher A. , Wines Bruce , Hogarth P. Mark , Kristensen Anne B. , Parsons Matthew S. , Purcell Damian F. J.
Published: April 2021

Despite successful antiviral chemotherapy, human immunodeficiency virus (HIV) is still a lifelong persistent virus, and no vaccine yet prevents HIV transmission. Topical microbicides offer an important alternative method to prevent sexual transmission of HIV-1.
Prazoles Targeting Tsg101 Inhibit Release of Epstein-Barr Virus following Reactivation from Latency
Authors: Mannemuddhu Sai Sudha , Xu Huanzhou , Bleck Christopher K. E. , Tjandra Nico , Carter Carol , Bhaduri-McIntosh Sumita
Published: April 2021

Production of virions is necessary for the ubiquitous Epstein-Barr virus (EBV) to persist in humans and can set the stage for development of EBV cancers in at-risk individuals. In our attempts to identify inhibitors of the EBV lytic phase, we previously found that a prazole proton pump inhibitor, known to block the interaction of ubiquitin with the ESCRT-1 factor Tsg101, blocks production of EBV.
3D Numerical Modeling of the Summit Lake Lava Flow, Yellowstone, USA
Authors: Tsepelev I. A. , Ismail-Zadeh A. T. , Melnik O. E.
Published: April 2021

Abstract—Volcanic eruptions belong to the extreme events that change the Earth’s landscape and affect global climate and environment. Although special attention is given to super-eruptions, the non-explosive rhyolitic (highly viscous) eruptions and large lava flows are no less important. In this paper, we study an ancient lava flow with a volume of ~50 km3 in the Summit Lake region, ​​Yellowstone, which is one of the best studied large intraplate igneous provinces. We develop three-dimensional (3D) numerical models of isothermal lava flow to analyze the influence of the underlying surface and lava flow viscosity on the advancement and duration of the flow. The modeled dynamics of flow propagation fairly well agrees with the measured values provided that the average angle of inclination of the underlying surface slightly differs from the present-day value (by ~1.3°) presumably due to the pressure change in the magma chamber during the eruption. With the increase in lava viscosity, the flow slows down and its thickness increases leading to a change in the flow morphology.
Recurrent pleural effusion secondary to endometriosis: a rare malady
Authors: Chittemsetti Seethala , Baikunje Nandakishore , Hosmane Giridhar Belur , Bhat Shubha
Published: April 2021

Thoracic endometriosis is a rare entity, wherein thoracic endometrial tissue deposition occurs. Recurrent pleural effusion is one of its manifestations. Diagnosis and treatment are often challenging, owing to the rarity of the condition and recurrences. We present an interesting case of a young woman of childbearing age who presented with recurrent haemorrhagic pleural effusion. She was referred to our centre after her initial video-assisted thoracoscopic biopsy was inconclusive. She was re-evaluated, and video-assisted thoracoscopic biopsy confirmed thoracic endometriosis. She underwent pleurodesis two times and currently on hormonal treatment, maintaining well.
Afebrile scrub typhus infection with cardiac manifestation
Authors: Manappallil Robin George , Nambiar Jayasree , Anil Revathy
Published: April 2021

Scrub typhus is an acute febrile disease transmitted via bites from mite larvae (chigger) infected with Orientia tsutsugamushi. Arrhythmias, ischaemic changes and QT prolongation are some of the observed ECG abnormalities. The patient being reported presented with angina and was found to have sinus bradycardia with ST elevation in inferior leads and T wave inversion in lateral leads. His coronary angiography was normal. Further evaluation leads to the diagnosis of scrub typhus infection. Following doxycycline therapy, his ECG became normal. Afebrile scrub typhus infection with cardiac manifestation is an uncommon scenario.
Iatrogenic common peroneal nerve injury during harvesting of semitendinosus tendon for anterior cruciate ligament reconstruction
Authors: Mens Raf , van Houten Albert , Brokelman Roy Bernardus Gerardus , Hoogeslag Roy
Published: April 2021

We present a case of iatrogenic injury to the common peroneal nerve (CPN) occurring due to harvesting of a hamstring graft, using a posterior mini-incision technique. A twitch of the foot was noted on retraction of the tendon stripper. After clinically diagnosing a CPN palsy proximal to the knee, the patient was referred to a neurosurgeon within 24 hours. An electromyography (EMG) was not obtained since it cannot accurately differentiate between partial and complete nerve injury in the first week after injury. Because the nerve might have been transacted by the tendon stripper, surgical exploration within 72 hours after injury was indicated. An intraneural haematoma was found and neurolysis was performed to decompress the nerve. Functioning of the anterior cruciate ligament was satisfactory during follow-up. Complete return of motor function of the CPN was observed at 1-year follow-up, with some remaining hypoaesthesia.
Incarcerated paraoesophageal hernia complicated with distal oesophageal perforation: a combined laparoscopic and endoscopic approach
Authors: Correia de Sá Tiago , Silva Jorge , Freitas Carla
Published: April 2021

Paraoesophageal hernias are common, but symptoms are not always present nor pathognomonic of this condition, and patients may be suffering for many years before a diagnosis is made. Incarceration and strangulation are rare, but they are life-threatening complications, warranting an emergent surgical repair. Hiatal hernia incarceration causing distal oesophagus perforation is even rarer. To our knowledge, this is the first case report in adult patients. Despite many advances in care, a high grade of suspicion is needed to diagnose this condition, and the mortality rate for an oesophageal perforation remains high, achieving 50% in some series. We present the surgical management of a case of hiatal hernia incarceration with distal oesophagus perforation by combined laparoscopy and upper endoscopy.
Management of straddling thrombus through patent foramen ovale complicating pulmonary embolism
Authors: Bhat Vijeth , lane Stuart , Orde Sam
Published: April 2021

A 60-year-old man was admitted to intensive care unit with the diagnosis of pulmonary embolism. Bedside transthoracic echocardiography revealed the extension of the thrombus into left atrium and ventricle through patent foramen ovale (PFO). A straddling thrombus also described as impending paradoxical embolism is a rare condition when thrombus embolised to the heart gets caught in PFO. Morbidity is extremely high in case of systemic embolisation. Due to rarity, the treatment options are mainly individualised and no guidelines exist. There are few treatment strategies described in literature from surgical to interventional radiology to conservative approach. Treatment strategy should take individual parameters such as patient’s age, haemodynamic stability, bleeding risk and comorbidities into consideration. Our patient successfully underwent emergency surgical thrombectomy.
Kawasaki disease with acute myocarditis in an adolescent
Authors: Shimizu Masato , Kaneda Toshio , Sekino Nagaaki , Nishizawa Takashi
Published: April 2021

A previously healthy 16-year-old adolescent was admitted to our hospital with fever, sore throat, diarrhoea, strawberry tongue, rashes on lower extremities, and pain in the neck, abdomen and joints. He was initially diagnosed with IgA vasculitis triggered by acute pharyngitis. Despite antibiotic treatment, he gradually developed multiorgan failure and cardiac shock. Cardiac catheterisation did not show any signs of coronary artery disease. Subsequently, he developed serious rhabdomyolysis and peripheral extremity necrosis, suggesting peripheral arteritis. Although blood culture results were negative, he received endotoxin adsorption therapy, but it was ineffective. Hence, we suspected Kawasaki disease (KD). We administered high-dose intravenous immunoglobulin therapy (2 g/kg), which was effective. He gradually recovered without major complications and was given ambulatory discharge 43 days after admission. Early diagnosis and administration of intensive care in adolescents with KD with acute myocarditis are critical but challenging.
Utilisation of musculoskeletal ultrasonography for the evaluation of septic arthritis in a patient presenting to the emergency department with fever during the era of COVID-19
Authors: Perez Jiodany , Sorensen Stefani , Rosselli Michael
Published: April 2021

Prompt recognition and treatment of septic arthritis are crucial to prevent significant morbidity and mortality in affected patients. During the current COVID-19 pandemic, anchoring bias may make an already challenging diagnosis like septic arthritis more difficult to diagnose quickly and efficiently. Musculoskeletal (MSK) point of care ultrasonography (POCUS) is an imaging modality that can be used to quickly and efficiently obtain objective findings that may help a clinician establish the diagnosis of septic arthritis. We report a case where MSK POCUS was a key element in establishing the diagnosis of glenohumeral joint septic arthritis and subdeltoid septic bursitis for a patient that presented to the emergency department with a fever during the era of the COVID-19 pandemic.
A systematic examination of international funding flows for Ebola virus and Zika virus outbreaks 2014–2019: donors, recipients and funding purposes
Authors: Quirk Emily Jade , Gheorghe Adrian , Hauck Katharina
Published: April 2021

Introduction

There has been no systematic comparison of how the policy response to past infectious disease outbreaks and epidemics was funded. This study aims to collate and analyse funding for the Ebola epidemic and Zika outbreak between 2014 and 2019 in order to understand the shortcomings in funding reporting and suggest improvements.

Methods

Data were collected via a literature review and analysis of financial reporting databases, including both amounts donated and received. Funding information from three financial databases was analysed: Institute of Health Metrics and Evaluation’s Development Assistance for Health database, the Georgetown Infectious Disease Atlas and the United Nations Financial Tracking Service. A systematic literature search strategy was devised and applied to seven databases: MEDLINE, EMBASE, HMIC, Global Health, Scopus, Web of Science and EconLit. Funding information was extracted from articles meeting the eligibility criteria and measures were taken to avoid double counting. Funding was collated, then amounts and purposes were compared within, and between, data sources.

Results

Large differences between funding reported by different data sources, and variations in format and methodology, made it difficult to arrive at precise estimates of funding amounts and purpose. Total disbursements reported by the databases ranged from $2.5 to $3.2 billion for Ebola and $150–$180 million for Zika. Total funding reported in the literature is greater than reported in databases, suggesting that databases may either miss funding, or that literature sources overreport. Databases and literature disagreed on the main purpose of funding for socioeconomic recovery versus outbreak response. One of the few consistent findings across data sources and diseases is that the USA was the largest donor.

Conclusion

Implementation of several recommendations would enable more effective mapping and deployment of outbreak funding for response activities relating to COVID-19 and future epidemics.
‘Food for Life and Palliation (FLiP)’: a qualitative study for understanding and empowering dignity and identity for terminally ill patients in Asia
Authors: Patinadan Paul Victor , Tan-Ho Geraldine , Choo Ping Ying , Low Casuarine Xinyi , Ho Andy Hau Yan
Published: April 2021

Objectives

With ‘eating’ posited as Singapore’s domestic pastime, food experiences for Singaporeans constitute national, social, ethnic and personal identities. However, though they form significant parts of Singaporean existence across the lifespan, studies and observations about food experiences for individuals at the end of life remain noticeably absent. Extant literature continues to focus on nutritional practice during illness and the active dying process, forgoing the rich lived experiences of food in the lives of patients and their families. The current work sought to qualitatively extricate through a constructivist phenomenological approach, the ‘food voices’ of Singaporean palliative care patients and their families. It also simultaneously aimed to assess the role of food in bolstering their subjective feelings of dignity and identity, while also considering resultant clinical implications.

Setting

Homes of patients within the Singaporean palliative care setting.

Participants

A subset of qualitative data (n=25) in the form of dyadic interviews with terminally ill patients and a family caregiver was generated from a larger family dignity intervention study that explored the experience of living and dying among Asian palliative care patients and their families.

Results

Framework analysis with both inductive and deductive approaches informed by the a priori domain of food resulted in the generation of four major themes, each with three subthemes. These were organised into the Food for Life and Palliation model. They include: (1) feeding identity and familial bonds, (2) liminal subsistence in illness transition, (3) food becoming lineage, and (4) compassionate nourishment.

Conclusions

Clinical implications are considered; including food-focused interventions that enhance dignity, promote meaning-making and facilitate legacy construction. Developmental suggestions are also directed at industry partners producing end-of-life nutrition products.
Air pollution, physical activity and ischaemic heart disease: a prospective cohort study of interaction effects
Authors: Raza Wasif , Krachler Benno , Forsberg Bertil , Sommar Johan Nilsson
Published: April 2021

Objective

To assess a possible interaction effect between physical activity and air pollution on first incidence of ischaemic heart disease (IHD).

Design

Prospective cohort study.

Setting

Umeå, Northern Sweden.

Participants

We studied 34 748 adult participants of Västerbotten Intervention Programme cohort from 1990 to January 2014. Annual particulate matter concentrations (PM2.5and PM10) at the participants’ residential addresses were modelled and a questionnaire on frequency of exercise and active commuting was completed at baseline. Cox proportional hazards modelling was used to estimate (1) association with physical activity at different levels of air pollution and (2) the association with particulate matter at different levels of physical activity.

Outcome

First incidence of IHD.

Results

Over a mean follow-up of 12.4 years, there were 1148 IHD cases. Overall, we observed an increased risk of IHD among individuals with higher concentrations of particles at their home address. Exercise at least twice a week was associated with a lower risk of IHD among participants with high residential PM2.5(hazard ratio (HR) 0.60; 95% CI: 0.44 to 0.82) and PM10(HR 0.55; 95% CI: 0.4 to 0.76). The same beneficial effect was not observed with low residential PM2.5(HR 0.94; 95% CI: 0.72 to 1.22) and PM10(HR 0.99; 95% CI: 0.76 to 1.29). An increased risk associated with higher long-term exposure to particles was only observed among participants that exercised in training clothes at most one a week and among those not performing any active commuting. However, only the interaction effect on HRs for exercise was statistically significant.

Conclusion

Exercise was associated with a lower risk of first incidence of IHD among individuals with higher residential particle concentrations. An air pollution-associated risk was only observed among those who exercised less. The findings support the promotion of physical activity and a mitigation of air pollution.
Symptom burden in multimorbidity: a population-based combined questionnaire and registry study from Denmark
Authors: Willadsen Tora Grauers , Siersma Volkert , Nicolaisdottir Dagny Ros , Jarbol Dorte , Guassora Ann Dorrit , Reventlow Susanne , Køster-Rasmussen Rasmus
Published: April 2021

Objective

Patients with multimorbidity may carry a large symptom burden. Symptoms are often what drive patients to seek healthcare and they also assist doctors with diagnosis. We examined whether symptom burden is additive in people with multimorbidity compared with people with a single morbidity.

Design

This is a longitudinal cohort study drawing on questionnaire and Danish national registry data. Multimorbidity was defined as having diagnoses from at least two out of ten morbidity groups. Associations between morbidity groups and symptom burden were estimated with multivariable models.

Participants

In 2012, 47 452 participants from the Danish Symptom Cohort answered a questionnaire about symptoms (36 symptoms in total), including whether symptoms were affecting their daily activities (impairment score) and their worries about present symptoms (worry score) (the highest score among the 36 symptoms on a 0–4 scale).

Main outcome measure

The primary outcome was symptom burden.

Results

Participants without morbidity reported 4.77 symptoms (out of 36 possible). Participants with one, two or three morbidities reported more symptoms than patients without morbidity (0.95 (CI 0.86 to 1.03), 1.87 (CI 1.73 to 2.01) and 2.89 (CI 2.66 to 3.12), respectively). Furthermore, they reported a higher impairment score (0.36 (0.32 to 0.39), 0.65 (0.60 to 0.70) and 1.06 (0.98 to 1.14)) and a higher worry score (0.34 (0.31 to 0.37), 0.62 (0.57 to 0.66) and 1.02 (0.94 to 1.10)) than participants without morbidity. In 45 possible combinations of multimorbidity (participants with two morbidities), interaction effects were additive in 37, 41 and 36 combinations for the number of symptoms, impairment score and worry score, respectively.

Conclusion

Participants without morbidity reported a substantial number of symptoms. Having a single morbidity or multimorbidity resulted in approximately one extra symptom for each extra morbidity. In most combinations of multimorbidity, symptom burden was additive.
How to manage quarantine—adherence, psychosocial consequences, coping strategies and lifestyle of patients with COVID-19 and their confirmed contacts: study protocol of the CoCo-Fakt surveillance study, Cologne, Germany
Authors: Joisten Christine , Kossow Annelene , Book Julian , Broichhaus Lukas , Daum Monika , Eisenburger Nina , Fabrice Alisa , Feddern Sven , Gehlhar Andreas , Graf Anna Carlotta , Grüne Barbara , Lorbacher Markus , Nießen Johannes , Noethig Wanja , Schmidt Nikola , Tappiser Marc , Wiesmüller Gerhard A
Published: April 2021

Introduction

The current coronavirus (SARS-CoV-2) pandemic has placed unprecedented restrictions on people’s lives and routines. To counteract the exponential spread of this virus, a lockdown was implemented in Germany in March 2020. Infected persons and their contacts were also quarantined. Compliance with quarantine measures is essential for containing the spread of the virus and avoiding incalculable consequences in terms of morbidity and mortality. On the other hand, prolonged homestays, particularly quarantining, may lead to fear, panic, anxiety and depression. Hence, determining the psychological response in people during quarantine and their coping strategies is relevant for the counselling and support of affected persons by healthcare workers.

Methods and analysis

The CoCo-Fakt-Survey (Cologne-Corona-Beratung und Unterstützung Für Index- und KontAKt-Personen während der Quarantäne-ZeiT; Cologne-Corona counselling and support for index and contacts during the quarantine period—author’s translation) will examine a cohort of persons in Cologne quarantined since the beginning of the SARS-CoV-2 outbreak during March 2020. The questionnaire will include demographic data, transmission route, health status, knowledge of and adherence to quarantine measurements, psychological impact on individuals and their family members including children, mental health status, and lifestyle (physical activity/sedentary behaviour, relaxation techniques, nutrition, smoking). All Cologne residents who needed to be quarantined due to a coronavirus infection and the individuals with whom they had contact will be surveyed.

Ethics and dissemination

No risks have been identified and no complications are expected. Ethics approval was obtained from the Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen Human Ethics Research Committee (351/20), and the research will be conducted in accordance with the approved protocol. The results will be disseminated through peer-reviewed journals and social medicine conferences.
Association between participation in the government subsidy programme for domestic travel and symptoms indicative of COVID-19 infection in Japan: cross-sectional study
Authors: Miyawaki Atsushi , Tabuchi Takahiro , Tomata Yasutake , Tsugawa Yusuke
Published: April 2021

Objective

To investigate the association between participation in government subsidies for domestic travel (subsidise up to 50% of all travel expenses) introduced nationally in Japan on 22 July 2020 and the incidence of symptoms indicative of COVID-19 infections.

Design

Cross-sectional analysis of nationally representative survey data.

Setting

Internet survey conducted between 25 August and 30 September 2020 in Japan. Sampling weights were used to calculate national estimates.

Participants

25 482 survey respondents (50.3% (12 809) women; mean (SD) age, 48.8 (17.4) years).

Main outcome measures

Incidence rate of five symptoms indicative of the COVID-19 infection (high fever, sore throat, cough, headache, and smell and taste disorder) within the past month of the survey, after adjustment for characteristics of individuals and prefecture fixed effects (effectively comparing individuals living in the same prefecture).

Results

At the time of the survey, 3289 (12.9%) participated in the subsidy programme. After adjusting for potential confounders, we found that participants in the subsidy programme exhibited higher incidence of high fever (adjusted rate, 4.7% for participants vs 3.7% for non-participants; adjusted OR (aOR) 1.83; 95% CI 1.34 to 2.48; p<0.001), sore throat (19.8% vs 11.3%; aOR 2.09; 95% CI 1.37 to 3.19; p=0.002), cough (19.0% vs 11.3%; aOR 1.96; 95% CI 1.26 to 3.01; p=0.008), headache (29.2% vs 25.5%; aOR 1.24; 95% CI 1.08 to 1.44; p=0.006) and smell and taste disorder (2.6% vs 1.8%; aOR 1.98; 95% CI 1.15 to 3.40; p=0.01) compared with non-participants. These findings remained qualitatively unaffected by additional adjustment for the use of 17 preventative measures (eg, social distancing, wearing masks and handwashing) and fear against the COVID-19 infection.

Conclusions

The participation of the government subsidy programme for domestic travel was associated with a higher probability of exhibiting symptoms indicative of the COVID-19 infection.
An evaluation of the implementation of quality improvement (QI) in primary care dentistry: a multi-method approach
Authors: Cassie Heather , Mistry Vinay , Beaton Laura , Black Irene , Clarkson Janet E , Young Linda
Published: April 2021

Objectives

Ensuring that healthcare is patient-centred, safe and harm free is the cornerstone of the NHS. The Scottish Patient Safety Programme (SPSP) is a national initiative to support the provision of safe, high-quality care. SPSP promotes a coordinated approach to quality improvement (QI) in primary care by providing evidence-based methods, such as the Institute for Healthcare Improvement’s Breakthrough Series Collaborative methodology. These methods are relatively untested within dentistry. The aim of this study was to evaluate the impact to inform the development and implementation of improvement collaboratives as a means for QI in primary care dentistry.

Design

A multimethod study underpinned by the Theoretical Domains Framework and the Kirkpatrick model. Quantitative data were collected using baseline and follow-up questionnaires, designed to explore beliefs and behaviours towards improving quality in practice. Qualitative data were gathered using interviews with dental team members and practice-based case studies.

Results

One hundred and eleven dental team members completed the baseline questionnaire. Follow-up questionnaires were returned by 79 team members. Twelve practices, including two case studies, participated in evaluation interviews. Findings identified positive beliefs and increased knowledge and skills towards QI, as well as increased confidence about using QI methodologies in practice. Barriers included time, poor patient and team engagement, communication and leadership. Facilitators included team working, clear roles, strong leadership, training, peer support and visible benefits. Participants’ knowledge and skills were identified as an area for improvement.

Conclusions

Findings demonstrate increased knowledge, skills and confidence in relation to QI methodology and highlight areas for improvement. This is an example of partnership working between the Scottish Government and NHSScotland towards a shared ambition to provide safe care to every patient. More work is required to evaluate the sustainability and transferability of improvement collaboratives as a means for QI in dentistry and wider primary care.
Effect of a multimethod quality improvement intervention on antipsychotic medication use among residents of long-term care
Authors: Hanson Heather M , Léveillé Tova , Cole Mollie , Soril Lesley JJ , Clement Fiona , Wagg Adrian , Silvius James
Published: April 2021

Background

Antipsychotic medications are used to address neuropsychiatric symptoms associated with dementia. Evidence suggests that among older adults with dementia, their harms outweigh their benefits. A quality improvement initiative was conducted to address inappropriate antipsychotic medication use in long-term care (LTC) in the province of Alberta.

Methods

We conducted a multimethod evaluation of the provincial implementation of the project in 170 LTC sites over a 3-year project period incorporating a quasi-experimental before–after design. Using a three-component intervention of education and audit and feedback delivered in a learning workshop innovation collaborative format, local LTC teams were supported to reduce the number of residents receiving antipsychotic medications in the absence of a documented indication. Project resources were preferentially allocated to supporting sites with the highest baseline antipsychotic medication use. Changes in antipsychotic medication use, associated clinical and economic outcomes, and the effects of the project on LTC staff, physicians, leaders and administrators, and family members of LTC residents were assessed at the conclusion of the implementation phase.

Results

The province-wide initiative was delivered with a 75% implementation fidelity. Inappropriate antipsychotic medication use declined from 26.8% to 21.1%. The decrease was achieved without unintended consequences in other outcomes including physical restraint use or aggressive behaviours. The project was more expensive but resulted in less inappropriate use of antipsychotics than the pre-project period (incremental cost per inappropriate antipsychotic avoided of $5 678.71). Accounts from family, organisational leaders, and LTC staff were supportive of the project activities and outcomes.

Conclusion

This quality improvement initiative was successfully delivered across an entire delivery arm of the continuing care sector. Quality of care in LTC was improved.
Developing the COVID-19 intensive care medical equipment distribution platform: outcomes and lessons learned
Authors: Akinluyi Emmanuel Adeoluwa , Stell David , Perera Nayanee , Sibley-Allen Christopher
Published: April 2021

During the first wave of the coronavirus pandemic, the UK government took the decision to centralise the procurement, allocation and distribution of mission-critical intensive care unit (ICU) medical equipment. Establishing new supply chains in the context of global shortages presented significant challenges. This report describes the development of an innovative platform developed rapidly and voluntarily by clinical engineers, to mobilise the UK’s shared medical equipment inventory, in order to match ICU capacity to dynamically evolving clinical demand. The ‘Coronavirus ICU Medical Equipment Distribution’ platform was developed to optimise ICU equipment allocation, distribution, collection, redeployment and traceability across the National Health Service. Although feedback on the platform has largely been very positive, the platform was built for a scenario that did not fully materialise in the UK and this affected the implementation approach. As such, it was not used to its full potential. Nonetheless, the platform and the insights derived and disseminated in its development have been extremely valuable. It provides a prototype for not only optimising system capacity in future pandemic scenarios but also a means for maximally exploiting the large amount of new equipment in the UK health system, as a result of the coronavirus pandemic. This early stage innovation has demonstrated that a system-wide pooled information resource can benefit the operations of individual organisations. It has also generated numerous lessons to be borne in mind in innovation projects.
Emergency department attendances during the COVID-19 pandemic: a retrospective analysis of attendances following Irish governmental pandemic measures
Authors: Sless Ryan Taylor , Hayward Nathaniel Edward , Ryan Paul MacDaragh , Deasy Conor , Dasari Kantikiran
Published: April 2021

Background

COVID-19 has resulted in the death of over 1 million people to date. Following government-implemented regulations, there has been concern over the apparent decline in emergency department (ED) attendances and the resultant health legacy. Therefore, we aimed to characterise the attendances to an Irish tertiary hospital ED following the implementation of these regulations during the COVID-19 pandemic.

Methods

This retrospective observational study investigated all attendances to the Cork University Hospital ED from 15 February to 11 April in 2020 and 2017–2019. Attendances were stratified into four periods: Before COVID (BC) (15 February to 5 March), After COVID (AC) (6 March to 12 March), Educational Closure (EC) (13 March to 27 March) and Stay Home (SH) (28 March to 11 April), as per government regulations. Triage presentations of abdominal pain, shortness of breath, chest pain, headache and trauma were examined. Data were analysed by independent t-tests and χ2analysis.

Results

There were 8261 attendances to the ED in the 2020 time period compared with a mean of 10 389 attendances during the corresponding periods in 2017–2019. There was a significant decrease in daily attendances in 2020 compared with 2017–2019 in the AC (142 vs 188, p=0.02), EC (122 vs 184, p<0.001) and SH (121 vs 181, p<0.001) periods, including significant decreases in abdominal pain (AC: 9 vs 22, EC: 10 vs 19, SH: 11 vs 18, p<0.001), chest pain (AC: 9 vs 15, EC: 8 vs 15, SH: 9 vs 15, p<0.01), headache (AC: 5 vs 11, EC: 4 vs 9, SH: 4 vs 9, p<0.01) and trauma (AC: 3 vs 5, EC: 2 vs 6, SH: 3 vs 5, p<0.01).

Conclusion

Our findings suggest that the combination of government-imposed restrictions and perceived risk of attending an ED during a pandemic may contribute to reduced attendances. Public confidence in EDs is necessary to reduce collateral damage caused by failure to seek medical attention during a pandemic; adequate infrastructure to allow social distancing and isolation capacity in EDs is a necessity.
Endoscopic full-thickness plication for the treatment of PPI-dependent GERD: results from a randomised, sham controlled trial
Authors: Kalapala Rakesh , Karyampudi Arun , Nabi Zaheer , Darisetty Santosh , Jagtap Nitin , Ramchandani Mohan , Gupta Rajesh , Lakhtakia Sundeep , Goud Rajesh , Venkat Rao G , Sharma Prateek , Reddy D Nageshwar
Published: April 2021

Background

The majority of endoscopic antireflux procedures for GERD are cumbersome to use and randomised long-term data are sparse. We conducted such a trial to determine the efficacy and safety of a novel, easy to use endoscopic full-thickness fundoplication (EFTP) device in patients with GERD.

Design

Patients with proton pump inhibitor (PPI)-dependent GERD were randomised to either EFTP or a sham procedure in 1:1 ratio. The primary endpoint was ≥50% improvement in the health-related quality of life (GERD-HRQL) score at 3 months. Secondary end points included improvement in GERD-HRQL, reflux symptom scores, PPI usage, oesophageal acid exposure and reflux episodes and endoscopic findings at 3, 6 and 12 months.

Results

Seventy patients were randomised; 35 in each group with a median (IQR) age of 36 (29–42) years, 71.4% males. 70% had non-erosive reflux disease on endoscopy with a mean DeMeester score of 18.9 (±19.93). The mean (±SD) duration of EFTP procedure was 17.4 (±4) min. The primary end point was more frequently achieved in the EFTP group (65.7% vs 2.9%; p<0.001). Median (IQR) % improvement in GERD-HRQL was significantly higher in the EFTP group at 6 (81.4 (60.9–100.0) versus 8.0 (2.2–21.6); p<0.001) and 12 (92.3 (84.4–100.0) versus 9.1 (4.8–36.0); p<0.001) months. In the EFTP group, 62.8% patients were off-PPI at 12 months compared with 11.4% in the sham group (p<0.001). pH-metry parameters partially improved at 3 months, (n=70; total reflux episodes in EFTP arm and non-acid reflux episodes for EFTP vs sham) but not at 12 months (n=27); endoscopic oesophagitis was seen in 0% in the treatment (n=18) and 5 (29.4%) in the control group (n=17) at 12 months. No major procedure-related adverse events were encountered in either group.

Conclusion

EFTP using a novel device is safe and effective in improving quality of life in patients with PPI dependent mostly non-erosive reflux disease at short and long terms; objective parameters showed a limited response rate.

Trial registration number

NCT03322553.
Heterogeneous distribution of tau pathology in the behavioural variant of Alzheimer’s disease
Authors: Singleton Ellen , Hansson Oskar , Pijnenburg Yolande A. L. , La Joie Renaud , Mantyh William G , Tideman Pontus , Stomrud Erik , Leuzy Antoine , Johansson Maurits , Strandberg Olof , Smith Ruben , Berendrecht Evi , Miller Bruce L , Iaccarino Leonardo , Edwards Lauren , Strom Amelia , Wolters Emma E , Coomans Emma , Visser Denise , Golla Sandeep S V , Tuncel Hayel , Bouwman Femke , Van Swieten John Cornelis , Papma Janne M , van Berckel Bart , Scheltens Philip , Dijkstra Anke A. , Rabinovici Gil D , Ossenkoppele Rik
Published: April 2021

Objective

The clinical phenotype of the rare behavioural variant of Alzheimer’s disease (bvAD) is insufficiently understood. Given the strong clinico-anatomical correlations of tau pathology in AD, we investigated the distribution of tau deposits in bvAD, in-vivo and ex-vivo, using positron emission tomography (PET) and postmortem examination.

Methods

For the tau PET study, seven amyloid-β positive bvAD patients underwent [18F]flortaucipir or [18F]RO948 PET. We converted tau PET uptake values into standardised (W-)scores, adjusting for age, sex and mini mental state examination in a ‘typical’ memory-predominant AD (n=205) group. W-scores were computed within entorhinal, temporoparietal, medial and lateral prefrontal, insular and whole-brain regions-of-interest, frontal-to-entorhinal and frontal-to-parietal ratios and within intrinsic functional connectivity network templates. For the postmortem study, the percentage of AT8 (tau)-positive area in hippocampus CA1, temporal, parietal, frontal and insular cortices were compared between autopsy-confirmed patients with bvAD (n=8) and typical AD (tAD;n=7).

Results

Individual regional W-scores ≥1.96 (corresponding to p<0.05) were observed in three cases, that is, case #5: medial prefrontal cortex (W=2.13) and anterior default mode network (W=3.79), case #2: lateral prefrontal cortex (W=2.79) and salience network (W=2.77), and case #7: frontal-to-entorhinal ratio (W=2.04). The remaining four cases fell within the normal distributions of the tAD group. Postmortem AT8 staining indicated no group-level regional differences in phosphorylated tau levels between bvAD and tAD (all p>0.05).

Conclusions

Both in-vivo and ex-vivo, patients with bvAD showed heterogeneous distributions of tau pathology. Since key regions involved in behavioural regulation were not consistently disproportionally affected by tau pathology, other factors are more likely driving the clinical phenotype in bvAD.
Time to get serious about distributed leadership: lessons to learn for promoting leadership development for non-consultant career grade doctors in the UK
Authors: Lagunes Cordoba Emmeline , Shale Suzanne , Evans Rachel Clare , Tracy Derek
Published: April 2021

COVID-19 has exposed the National Health Service (NHS) to the greatest challenge in its existence, highlighting the need for nimble, reactive and inclusive leadership. It is set against a backdrop of a workforce recruitment and retention crisis predicted to worsen in coming years. There is a need to do things differently in healthcare, including better diversity and distribution of leadership. We make the case for senior non-consultant doctors, in the UK more usually referred to as specialty and associate specialist or locally employed doctors. These skilled, experienced medics have much to offer yet are frequently overlooked, with little guidance or support from central organisations and medical colleges or within NHS Trusts themselves. In this commentary, we suggest ways this workforce might be better tapped into, to the benefit of patients and healthcare systems, as well as the doctors themselves.
Making a case for the inclusion of refractory and severe mental illness as a sole criterion for Canadians requesting medical assistance in dying (MAiD): a review
Authors: Bahji Anees , Delva Nicholas
Published: April 2021

Background

Following several landmark rulings and increasing public support for physician-assisted death, in 2016, Canada became one of a handful of countries legalising medical assistance in dying (MAiD) with Bill C-14. However, the revised Bill C-7 proposes the specific exclusion of MAiD where a mental disorder is the sole underlying medical condition (MAiD MD-SUMC).

Aim

This review explores how some persons with serious and persistent mental illness (SPMI) could meet sensible and just criteria for MAiD under the Canadian legislative framework.

Methods

We review the proposed Bill C-7 criteria (capacity, voluntariness, irremediability and suffering) as well as the nuances involved in separating a well-reasoned request for assisted suicide from what might be solely a manifestation of a SPMI.

Findings

In this paper, we argue against the absolute exclusion of patients with SPMIs from accessing MAiD. Instead, we propose that in some circumstances, MAiD MD-SUMC may be justifiable while remaining the last resort. Conducting MAiD eligibility assessments removes the need to introduce diagnosis-specific language into MAiD legislation. Competent psychiatric patients who request MAiD should not be treated any differently from other eligible candidates. Many individuals with psychiatric disorders will be incapable of consenting to MAiD. The only ethical option is to assess eligibility for MAiD on an individual basis and include as legitimate candidates those who suffer solely from psychiatric illness who have the decisional capacity to consent to MAiD.
Anticoagulation in COVID-19: current concepts and controversies
Authors: Chandra Atanu , Chakraborty Uddalak , Ghosh Shrestha , Dasgupta Sugata
Published: April 2021

Rising incidence of thromboembolism secondary to COVID-19 has become a global concern, with several surveys reporting increased mortality rates. Thrombogenic potential of the SARS-CoV-2 virus has been hypothesised to originate from its ability to produce an exaggerated inflammatory response leading to endothelial dysfunction. Anticoagulants have remained the primary modality of treatment of thromboembolism for decades. However, there is no universal consensus regarding the timing, dosage and duration of anticoagulation in COVID-19 as well as need for postdischarge prophylaxis. This article seeks to review the present guidelines and recommendations as well as the ongoing trials on use of anticoagulants in COVID-19, identify discrepancies between all these, and provide a comprehensive strategy regarding usage of these drugs in the current pandemic.
Adult-onset subacute sclerosing panencephalitis
Authors: Nair Sruthi S , Vysakha K V , Menon Ramshekhar N , Sundaram Soumya
Published: April 2021

Subacute sclerosing panencephalitis (SSPE) is a lethal slow viral disease of the central nervous system caused by a defective measles virus. The onset is mostly in childhood, manifesting clinically as decline in academic performance, behavioural changes, motor dysfunction and myoclonus. Adult-onset SSPE is rare and can present as rapidly progressive dementia. We present a young man of Indian origin with adult-onset SSPE with rapidly progressive dementia but no localising neurological signs. The diagnostic clues were parieto-occipital white matter changes on MR brain scan and history of childhood fever with rash. High titres of antimeasles antibody in cerebrospinal fluid confirmed the diagnosis. The long latency from primary measles virus infection to symptom onset can be misleading in adults. SSPE should be considered in adults with dementia, especially in tropical countries where vaccination coverage is suboptimal.
Wasp sting-related allergic encephalitis
Authors: Maramattom Boby Varkey
Published: April 2021

A 48-year-old man presented with a headache and disorientation after multiple wasp stings. Following admission, he developed seizures and was intubated. We provisionally diagnosed wasp sting-related allergic encephalitis and treated this with intravenous methylprednisolone and intravenous immunoglobulin. He recovered uneventfully over several days.
Outcomes of major trauma among patients with chronic kidney disease and receiving dialysis in Nova Scotia: a retrospective analysis
Authors: Pratt Ryan , Erdogan Mete , Green Robert , Clark David , Vinson Amanda , Tennankore Karthik
Published: April 2021

Background

The risk of death and complications after major trauma in patients with chronic kidney disease (CKD) is higher than in the general population, but whether this association holds true among Canadian trauma patients is unknown.

Objectives

To characterize patients with CKD/receiving dialysis within a regional major trauma cohort and compare their outcomes with patients without CKD.

Methods

All major traumas requiring hospitalization between 2006 and 2017 were identified from a provincial trauma registry in Nova Scotia, Canada. Trauma patients with stage ≥3 CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) or receiving dialysis were identified by cross-referencing two regional databases for nephrology clinics and dialysis treatments. The primary outcome was in-hospital mortality; secondary outcomes included hospital/intensive care unit (ICU) length of stay (LOS) and ventilator-days. Cox regression was used to adjust for the effects of patient characteristics on in-hospital mortality.

Results

In total, 6237 trauma patients were identified, of whom 4997 lived within the regional nephrology catchment area. CKD/dialysis trauma patients (n=101; 28 on dialysis) were older than patients without CKD (n=4896), with higher rates of hypertension, diabetes, and cardiovascular disease, and had increased risk of in-hospital mortality (31% vs 11%, p<0.001). No differences were observed in injury severity, ICU LOS, or ventilator-days. After adjustment for age, sex, and injury severity, the HR for in-hospital mortality was 1.90 (95% CI 1.33 to 2.70) for CKD/dialysis compared with patients without CKD.

Conclusion

Independent of injury severity, patients without CKD/dialysis have significantly increased risk of in-hospital mortality after major trauma.