bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual topography of laminin corona on gallium arsenide nanowires
Authors: Gunnarsson Stefán Bragi , Mellace Cesare , Bernfur Katja , Sivakumar Sudhakar , Magnusson Martin H. , Cedervall Tommy
Published: October 2020

Nanowires (NWs) are novel nanomaterials with applications in everything from medical implants to solar cells. With increasing number of applications, it is increasingly likely that organisms are exposed to these materials either intentionally or by accident. It is, therefore, important to study their interactions with biological systems and biomolecules. Upon exposure to biological fluids, nanostructure surfaces are quickly covered by a biomolecule corona. The composition of the corona determines the nanostructure's biological fate. Furthermore, upon adsorption, the protein structure can be affected. In order to study the corona morphology, we used two model proteins, laminin of the extracellular matrix and the immune system enzyme myeloperoxidase. We image the protein corona directly by cryo-TEM and enhance resolution by labeling the corona with activated gold nanoparticles. Three-dimensional imaging of the protein corona further increases the resolution and reveals irregularities in corona topography. By doing so, we identified bimodal distribution of spacing between gold nanoparticles and the NW surface for laminin corona at 58 and 85 nm distance from the NWs’ surface. The dual topography of the corona is adding a new complexity of the protein corona surface and its interactions with the surrounding biology.
Crocodiles use both interaural level differences and interaural time differences to locate a sound source
Authors: Papet L. , Raymond M. , Boyer N. , Mathevon N. , Grimault N.
Published: October 2020

To explore how crocodilians locate a sound source, two Nile crocodiles (Crocodylus niloticus) were trained to swim towards an acoustic target. Using filtered versions of synthesized stimuli, the respective roles of interaural level differences (ILDs) and interaural time differences (ITDs), which are the two main cues providing information on sound source position, were tested. This study shows that crocodiles rely on both ILDs and ITDs to locate the spatial direction of a sound source and that their performance is lower when one of the cues is lacking.
KPC Beta-Lactamases Are Permissive to Insertions and Deletions Conferring Substrate Spectrum Modifications and Resistance to Ceftazidime-Avibactam
Authors: Hobson Claire Amaris , Bonacorsi Stéphane , Jacquier Hervé , Choudhury Alaksh , Magnan Mélanie , Cointe Aurélie , Bercot Béatrice , Tenaillon Olivier , Birgy André
Published: October 2020

To explore the mutational possibilities of insertions and deletions (indels) in the
Klebsiella pneumoniae
carbapenemase (KPC) beta-lactamase, we selected for ceftazidime-avibactam-resistant mutants. Of 96 screened mutants, we obtained 19 indels (2 to 15 amino acids), all located in the loops surrounding the active site. Three antibiotic susceptibility phenotypes emerged: an extended-spectrum-beta-lactamase-like phenotype, an activity restricted to ceftazidime, and a carbapenem-susceptible KPC-like phenotype.
Pharmacokinetic Model for Cefuroxime Dosing during Cardiac Surgery under Cardiopulmonary Bypass
Authors: Lanoiselée J. , Zufferey P. J. , Hodin S. , Tamisier N. , Gergelé L. , Palao J. C. , Campisi S. , Molliex S. , Morel J. , Delavenne X. , Ollier E.
Published: October 2020

Cefuroxime (CXM) is an antibiotic recommended for surgical site infection prevention in cardiac surgery. However, the dosing regimens commonly used do not sustain therapeutic concentrations throughout surgery. The aim of this study was to conduct a population analysis of CXM pharmacokinetics (PK), and to propose an optimized dosing regimen. Adult patients undergoing cardiac surgery under cardiopulmonary bypass (CPB) received a 1,500 mg CXM intravenous bolus followed by a 750 mg bolus at CPB priming, then every 2 h thereafter.
CaaX-Like Protease of Cyanobacterial Origin Is Required for Complex Plastid Biogenesis in Malaria Parasites
Authors: Meister Thomas R. , Tang Yong , Pulkoski-Gross Michael J. , Yeh Ellen
Published: October 2020

Plasmodium
parasites, which cause malaria, and related apicomplexans are important human and veterinary pathogens. These parasites represent a highly divergent and understudied branch of eukaryotes, and as such often defy the expectations set by model organisms. One striking example of unique apicomplexan biology is the apicoplast, an essential but nonphotosynthetic plastid derived from an unusual secondary (eukaryote-eukaryote) endosymbiosis. Endosymbioses are a major driver of cellular innovation, and apicoplast biogenesis pathways represent a hot spot for molecular evolution. We previously conducted an unbiased screen for apicoplast biogenesis genes in
P. falciparum
to uncover these essential and innovative pathways. Here, we validate a novel gene candidate from our screen and show that its role in apicoplast biogenesis does not match its functional annotation predicted by model eukaryotes. Our findings suggest that an uncharacterized chloroplast maintenance pathway has been reused for complex plastid biogenesis in this divergent branch of pathogens.
The Glycoprotease CpaA Secreted by Medically Relevant Acinetobacter Species Targets MultipleO-Linked Host Glycoproteins
Authors: Haurat M. Florencia , Scott Nichollas E. , Di Venanzio Gisela , Lopez Juvenal , Pluvinage Benjamin , Boraston Alisdair B. , Ferracane Michael J. , Feldman Mario F.
Published: October 2020

CpaA is a glycoprotease expressed by members of theAcinetobacter baumannii-calcoaceticuscomplex, and it is the first bona fide secreted virulence factor identified in these species. Here, we show that CpaA cleaves multiple targets precisely atO-glycosylation sites preceded by a Pro residue. This feature, together with the observation that sialic acid does not impact CpaA activity, makes this enzyme an attractive tool for the analysis ofO-linked human protein for biotechnical and diagnostic purposes. Previous work identified proteins involved in blood coagulation as targets of CpaA. Our work broadens the set of targets of CpaA, pointing toward additional roles in bacterium-host interactions. We propose that CpaA belongs to an expanding class of functionally defined glycoproteases that targets multipleO-linked host glycoproteins.
Broad-Spectrum Antimicrobial and Antibiofilm Activity of a Natural Clay Mineral from British Columbia, Canada
Authors: Behroozian Shekooh , Svensson Sarah L. , Li Loretta Y. , Davies Julian E.
Published: October 2020

The escalating emergence of multidrug-resistant (MDR) bacteria, together with the paucity of novel antimicrobial agents in antibiotic development, is recognized as a worldwide public health crisis. Kisameet clay (KC), found in British Columbia (BC), Canada, is a clay mineral with a long history of therapeutic applications among people of the First Nations. We previously reported the antibacterial activity of KC against a group of MDR clinical pathogens. Here, we demonstrate its activity against two major human-pathogenic fungal species, as well as against bacterial biofilms, which underlie many recalcitrant bacterial infections. In these studies, we also identified several geochemical characteristics of KC, such as metal ions and low pH, which are involved in its antibacterial activity. These findings provide a better understanding of the components of KC antibacterial activity and a basis for developing defined preparations of this clay mineral for therapeutic applications.
Survival Strategies of Pathogenic
Candida
Species in Human Blood Show Independent and Specific Adaptations
Authors: Kämmer Philipp , McNamara Sylvie , Wolf Thomas , Conrad Theresia , Allert Stefanie , Gerwien Franziska , Hünniger Kerstin , Kurzai Oliver , Guthke Reinhard , Hube Bernhard , Linde Jörg , Brunke Sascha
Published: October 2020

To ensure their survival, pathogens have to adapt immediately to new environments in their hosts, for example, during the transition from the gut to the bloodstream. Here, we investigated the basis of this adaptation in a group of fungal species which are among the most common causes of hospital-acquired infections, the
Candida
species. On the basis of a human whole-blood infection model, we studied which genes and processes are active over the course of an infection in both the host and four different
Candida
pathogens. Remarkably, we found that, while the human host response during the early phase of infection is predominantly uniform, the pathogens pursue largely individual strategies and each one regulates genes involved in largely disparate processes in the blood. Our results reveal that
C. albicans
,
C. glabrata
,
C. parapsilosis
, and
C. tropicalis
all have developed individual strategies for survival in the host. This indicates that their pathogenicity in humans has evolved several times independently and that genes which are central for survival in the host for one species may be irrelevant in another.
Subacromial decompression versus diagnostic arthroscopy for shoulder impingement: a 5-year follow-up of a randomised, placebo surgery controlled clinical trial
Authors: Paavola Mika , Kanto Kari , Ranstam Jonas , Malmivaara Antti , Inkinen Jari , Kalske Juha , Savolainen Vesa , Sinisaari Ilkka , Taimela Simo , Järvinen Teppo L
Published: October 2020

Objectives

To assess the long-term efficacy of arthroscopic subacromial decompression (ASD) by comparing it with diagnostic arthroscopy (primary comparison), a placebo surgical intervention, and with a non-operative alternative, exercise therapy (secondary comparison).

Methods

We conducted a multicentre, three group, randomised, controlled superiority trial. We included 210 patients aged 35–65 years, who had symptoms consistent with shoulder impingement syndrome for more than 3 months. 175 participants (83%) completed the 5 years follow-up. Patient enrolment began on 1 February 2005 and the 5-year follow-up was completed by 10 October 2018. The two primary outcomes were shoulder pain at rest and on arm activity measured with Visual Analogue Scale (VAS). Minimally important difference (MID) was set at 15. We used a mixed-model repeated measurements analysis of variance with participant as a random factor, the baseline value as a covariate and assuming a covariance structure with compound symmetry.

Results

In the primary intention to treat analysis (ASD vs diagnostic arthroscopy), there were no between-group differences that exceeded the MID for the primary outcomes at 5 years: the mean difference between groups (ASD minus diagnostic arthroscopy) in pain VAS were −2.0 (95% CI −8.5 to 4.6; p=0.56) at rest and −8.0 (−17.3 to 1.3; p=0.093) on arm activity. There were no between-group differences in the secondary outcomes or adverse events that exceeded the MID. In our secondary comparison (ASD vs exercise therapy), the mean differences between groups (ASD minus exercise therapy) in pain VAS were 1.0 (−5.6 to 7.6; p=0.77) at rest and −3.9 (−12.8 to 5.1; p=0.40) on arm activity. There were no significant between-group differences for the secondary outcomes or adverse events.

Conclusions

ASD provided no benefit over diagnostic arthroscopy (or exercise therapy) at 5 years for patients with shoulder impingement syndrome.
Is extensive cardiopulmonary screening useful in athletes with previous asymptomatic or mild SARS-CoV-2 infection?
Authors: Gervasi Salvatore Francesco , Pengue Luca , Damato Luca , Monti Riccardo , Pradella Silvia , Pirronti Tommaso , Bartoloni Alessandro , Epifani Francesco , Saggese Alessio , Cuccaro Francesco , Bianco Massimiliano , Zeppilli Paolo , Palmieri Vincenzo
Published: October 2020

Objective

During the COVID-19 pandemic, it is essential to understand if and how to screen SARS-CoV-2-positive athletes to safely resume training and competitions. The aim of this study is to understand which investigations are useful in a screening protocol aimed at protecting health but also avoiding inappropriate examinations.

Methods

We conducted a cohort study of a professional soccer team that is based on an extensive screening protocol for resuming training during the COVID-19 pandemic. It included personal history, antigen swabs, blood tests, spirometry, resting/stress-test ECG with oxygen saturation monitoring, echocardiogram, Holter and chest CT. We also compared the findings with prior data from the same subjects before infection and with data from SARS-CoV-2-negative players.

Results

None of the players had positive swab and/or anti-SARS-CoV-2 IgM class antibodies. Out of 30 players, 18 (60%) had IgG class antibodies. None had suffered severe SARS-CoV-2-related disease, 12 (66.7%) had complained of mild COVID-19-related symptoms and 6 (33.3%) were asymptomatic. None of the players we examined revealed significant cardiovascular abnormalities after clinical recovery. A mild reduction in spirometry parameters versus pre-COVID-19 values was observed in all athletes, but it was statistically significant (p<0.05) only in SARS-CoV-2-positive athletes. One SARS-CoV-2-positive player showed increased troponin I level, but extensive investigation did not show signs of myocardial damage.

Conclusion

In this small cohort of athletes with previous asymptomatic/mild SARS-CoV-2 infection, a comprehensive screening protocol including blood tests, spirometry, resting ECG, stress-test ECG with oxygen saturation monitoring and echocardiogram did not identify relevant anomalies. While larger studies are needed, extensive cardiorespiratory and haematological screening in athletes with asymptomatic/mild SARS-CoV-2 infection appears unnecessary.
Metabolomic, hormonal and physiological responses to hypoglycemia versus euglycemia during exercise in adults with type 1 diabetes
Authors: McCarthy Olivia , Pitt Jason , Churm Rachel , Dunseath Gareth J , Jones Charlotte , Bally Lia , Nakas Christos T , Deere Rachel , Eckstein Max L , Bain Stephen C , Moser Othmar , Bracken Richard M
Published: October 2020

Introduction

This study sought to compare the metabolomic, hormonal and physiological responses to hypoglycemia versus euglycemia during exercise in adults with type 1 diabetes (T1D).

Research design and methods

Thirteen individuals with T1D (hemoglobin; 7.0%±1.3% (52.6±13.9 mmol/mol), age; 36±15 years, duration diabetes; 15±12 years) performed a maximum of 45 min submaximal exercise (60%±6% V̇O2max). Retrospectively identified exercise sessions that ended in hypoglycemia ((HypoEx) blood glucose (BG)≤3.9 mmol/L) were compared against a participant-matched euglycemic condition ((EuEx) BG≥4.0, BG≤10.0 mmol/L). Samples were compared for detailed physiological and hormonal parameters as well as metabolically profiled via large scale targeted ultra-high-performance liquid chromatography coupled to tandem mass spectrometry. Data were assessed using univariate and multivariate analysis techniques with false discovery rate adjustment. Significant results were considered at p≤0.05.

Results

Cardiorespiratory and counterregulatory hormone responses, whole-body fuel use and perception of fatigue during exercise were similar under conditions of hypoglycemia and euglycemia (BG 3.5±0.3 vs 5.8±1.1 mmol/L, respectively p<0.001). HypoEx was associated with greater adenosine salvage pathway activity (5’-methylthioadenosine, p=0.023 and higher cysteine and methionine metabolism), increased utilization of glucogenic amino acids (glutamine, p=0.021, alanine, aspartate and glutamate metabolism and homoserine/threonine, p=0.045) and evidence of enhanced β-oxidation (lower carnitine p<0.001, higher long-chain acylcarnitines).

Conclusions

Exposure to acute hypoglycemia during exercise potentiates alterations in subclinical indices of metabolic stress at the level of the metabolome. However, the physiological responses induced by dynamic physical exercise may mask the symptomatic recognition of mild hypoglycemia during exercise in people with T1D, a potential clinical safety concern that reinforces the need for diligent glucose management.

Trial registration number

DRKS00013509.
Association of care workers’ job satisfaction and global happiness with change of functional performance of severely disabled elderly residents in nursing homes: a cohort and questionnaire study in Japan
Authors: Ikeda-Sonoda Shino , Ichihara Nao , Okochi Jiro , Takahashi Arata , Miyata Hiroaki
Published: October 2020

Objectives

There is growing concern regarding quality of work life (QWL) among care staff in nursing homes. However, little is known about the impact of QWL on nursing home residents’ functional performance. Recent literature suggests that job satisfaction and happiness of healthcare workers reflect their perceived QWL and impact the quality of their care. This study examined the association between job satisfaction and global happiness with change in functional performance of severely disabled elderly residents in nursing homes.

Design

A retrospective cohort study of nursing home residents combined with a questionnaire survey of their care staff.

Setting

Eighteen nursing homes in Japan.

Participants

Data were collected from 1000 residents with a required care level of 3–5 and from 412 care staff in nursing homes between October 2017 and March 2018.

Outcomes and explanatory variables

Functional performance was structurally assessed with ICF (International Classification of Functioning, Disability and Health) staging, composed of 52 items concerning activities of daily life, cognitive function and social participation, at baseline and 6 months later. Deterioration and improvement of functional performance were dichotomously defined as such change in any of the items. QWL of care staff was evaluated with a questionnaire including questions about job satisfaction and global happiness.

Results

Functional performance deteriorated and improved in 23.0% and 12.7% of residents, respectively. Global happiness of care staff was associated with lower probability of residents’ deterioration (adjusted OR, 0.61; CI 0.44 to 0.84). There was no significant correlation between job satisfaction or happiness of care staff and improvement of residents’ functional performance.

Conclusion

These results suggest that QWL of care staff is associated with changes in functional performance of elderly people with severe disabilities in nursing homes.
PartnerCARE—a psycho-oncological online intervention for partners of patients with cancer: study protocol for a randomised controlled feasibility trial
Authors: Bodschwinna Daniela , Lorenz Inga , Bauereiss Natalie , Gündel Harald , Baumeister Harald , Hoenig Klaus
Published: October 2020

Introduction

Cancer burdens not only the patient but also the partner to a comparable extent. Partners of patients with cancer are highly involved in the caring process and therefore often experience distress and report a low quality of life. Interventions for supporting partners are scarce. Existing ones are rarely used by partners because they are often time-consuming per se and offer only limited flexibility with regard to schedule and location. The online intervention PartnerCARE has been developed on the basis of caregiver needs and consists of six consecutive sessions and four optional sessions, which are all guided by an e-coach. The study aims to evaluate feasibility and acceptance of the online intervention PartnerCARE and the related trial process. In addition, first insights of the putative efficacy of PartnerCARE should be gained.

Methods and analysis

A two-arm parallel-group randomised controlled trial will be conducted to compare the PartnerCARE online intervention with a waitlist control group. The study aims to recruit in total n=60 partners of patients with any type of cancer across different access paths (eg, university medical centres, support groups, social media). Congruent with feasibility study objectives, the primary outcome comprises recruitment process, study procedure, acceptance and satisfaction with the intervention (Client Satisfaction Questionnaire adapted to Internet-based interventions), possible negative effects (Inventory of Negative Effects in Psychotherapy) and dropout rates. Secondary outcomes include quality of life, distress, depression, anxiety, caregiver burden, fear of progression, social support, self-efficacy, coping and loneliness. Online measurements will be performed by self-assessment at three time points (baseline/pre-randomisation, 2 months and 4 months after randomisation). Data analyses will be based on intention-to-treat principle.

Ethics and dissemination

Ethics approval has been granted by the Ethics Committee of the University of Ulm (No 390/18). Results from this study will be disseminated to relevant healthcare communities, in peer-reviewed journals and at scientific and clinical conferences.

Trial registration number

DRKS00017019.
Outbreak response intervention models of vaccine-preventable diseases in humans and foot-and-mouth disease in livestock: a protocol for a systematic review
Authors: Azam James M , Are Elisha B , Pang Xiaoxi , Ferrari Matthew J , Pulliam Juliet R C
Published: October 2020

Introduction

Outbreaks of vaccine-preventable diseases continue to threaten public health, despite the proven effectiveness of vaccines. Interventions such as vaccination, social distancing and palliative care are usually implemented, either individually or in combination, to control these outbreaks. Mathematical models are often used to assess the impact of these interventions and for supporting outbreak response decision making. The objectives of this systematic review, which covers all human vaccine-preventable diseases, are to determine the relative impact of vaccination compared with other outbreak interventions, and to ascertain the temporal trends in the use of modelling in outbreak response decision making. We will also identify gaps and opportunities for future research through a comparison with the foot-and-mouth disease outbreak response modelling literature, which has good examples of the use of modelling to inform outbreak response intervention decision making.

Methods and analysis

We searched on PubMed, Scopus, Web of Science, Google Scholar and some preprint servers from the start of indexing to 15 January 2020. Inclusion: modelling studies, published in English, that use a mechanistic approach to evaluate the impact of an outbreak intervention. Exclusion: reviews, and studies that do not describe or use mechanistic models or do not describe an outbreak. We will extract data from the included studies such as their objectives, model types and composition, and conclusions on the impact of the intervention. We will ascertain the impact of models on outbreak response decision making through visualisation of time trends in the use of the models. We will also present our results in narrative style.

Ethics and dissemination

This systematic review will not require any ethics approval since it only involves scientific articles. The review will be disseminated in a peer-reviewed journal and at various conferences fitting its scope.

PROSPERO registration number

CRD42020160803.
Lived experiences of palliative care among people living with HIV/AIDS: a qualitative study from Bihar, India
Authors: Nair Mohit , Kumar Pragya , Mahajan Raman , Harshana Amit , Richardson Kathryn , Moreto-Planas Laura , Burza Sakib
Published: October 2020

Objectives

This study aimed to assess the lived experiences of palliative care among critically unwell people living with HIV/AIDS (PLHA), caregivers and relatives of deceased patients. It also aimed to understand the broader palliative care context in Bihar.

Design

This was an exploratory, qualitative study which used thematic analysis of semistructured, in-depth interviews as well as a focus group discussion.

Setting

All interviews took place in a secondary care hospital in Patna, Bihar which provides holistic care to critically unwell PLHA.

Participants

We purposively selected 29 participants: 10 critically unwell PLHA, 5 caregivers of hospitalised patients, 7 relatives of deceased patients who were treated in the secondary care hospital and 7 key informants from community-based organisations.

Results

Critically ill PLHA emphasised the need for psychosocial counselling and opportunities for social interaction in the ward, as well as a preference for components of home-based palliative care, even though they were unfamiliar with actual terms such as ‘palliative care’ and ‘end-of-life care’. Critically unwell PLHA generally expressed preference for separate, private inpatient areas for end-of-life care. Relatives of deceased patients stated that witnessing patients’ deaths caused trauma for other PLHA. Caregivers and relatives of deceased patients felt there was inadequate time and space for grieving in the hospital. While both critically ill PLHA and relatives wished that poor prognosis be transparently disclosed to family members, many felt it should not be disclosed to the dying patients themselves.

Conclusions

Despite expected high inpatient fatality rates, PLHA in Bihar lack access to palliative care services. PLHA receiving end-of-life care in hospitals should have a separate dedicated area, with adequate psychosocial counselling and activities to prevent social isolation. Healthcare providers should make concerted efforts to inquire, understand and adapt their messaging on prognosis and end-of-life care based on patients’ preferences.
AGT-Reha-WK study: protocol for a non-inferiority trial comparing the efficacy and costs of home-based telerehabilitation for shoulder diseases with medical exercise therapy
Authors: Steiner Bianca , Elgert Lena , Haux Reinhold , Wolf Klaus-Hendrik
Published: October 2020

Introduction

Shoulder lesions rank among the top 15 diagnoses accounting for days of incapacity to work. Inpatient or full-day outpatient rehabilitation are some of the standard therapies. For sustainable rehabilitation, continuation of rehabilitation after discharge from a rehabilitation centre is vital. Besides medical exercise therapy (MET), home-based physical exercise programmes are used. To monitor exercise quantity and quality, AGT-Reha, a health-enabling technology for home rehabilitation, has been developed and evaluated in a pilot study for technical feasibility and acceptance. To integrate the digital therapeutic AGT-Reha into regular healthcare processes, an efficacy evaluation is required.

Methods and analysis

AGT-Reha-WK is a prospective, monocentric, non-randomised, unblinded non-inferiority trial. Primary objective is to investigate whether AGT-Reha enhanced home-based exercise training is non-inferior to MET as standard aftercare. Secondary objective is to compare the costs of both therapies. Efficacy as medical success (primary outcome) is examined with regard to ability to work, return to work and sustainability of training (secondary outcomes). The outcome measure for non-inferiority is shoulder function (pain and disability) assessed by the standardised Shoulder Pain and Disability Index (SPADI). The non-inferiority margin is set to 10 points on SPADI score using a 95% CI. Subjects will be recruited at the Rehabilitation Center Bad Pyrmont, Germany. The total number of subjects should be 84 (42 per group). Treatment takes 6 months per patient. Subjects will be assessed at four time points: pre-baseline (admission to rehabilitation centre), baseline (discharge from rehabilitation centre), post-therapy and follow-up (3 months post-therapy).

Ethics and dissemination

Ethics approval was granted by the Ethics Committee of Hannover Medical School (ethics approval no: 7313). Results of the trial are planned to be published in a peer-reviewed journal.

Trial registration number

German Clinical Trials Register DRKS00011596. Registered 2 June 2017. Recruitment started on 3 March 2017, and it is expected to continue until December 2020.

Protocol version

V2.0, 23 May 2018, Amendment 01: improved risk analysis, clarification of exclusion criteria to increase reproducibility, additional documentation with OpenClinica; these changes have no effect on structural equality.
COproduction VALUE creation in healthcare service (CO-VALUE): an international multicentre protocol to describe the application of a model of value creation for use in systems of coproduced healthcare services and to evaluate the initial feasibility, utility and acceptability of associated system-level value creation assessment approaches
Authors: Oliver Brant J , Batalden Paul B , DiMilia Peter Rocco , Forcino Rachel C , Foster Tina C , Nelson Eugene C , Garre Boel Anderson
Published: October 2020

Introduction

Coproduction introduces a fundamental shift in how healthcare service is conceptualised. The mechanistic idea of healthcare being a ‘product’ generated by the healthcare system and delivered to patients is replaced by that of a service co-created by the healthcare system and the users of healthcare services. Fjeldstad et al offer an approach for conceptualising value creation in complex service contexts that we believe is applicable to coproduction of healthcare service. We have adapted Fjeldstad’s value creation model based on a detailed case study of a renal haemodialysis service in Jonkoping, Sweden, which demonstrates coproduction characteristics and key elements of Fjeldstad’s model.

Methods and analysis

We propose a five-part coproduction value creation model for healthcare service: (1) value chain, characterised by a standardised set of processes that serve a commonly occurring need; (2) value shop, which offers a customised response for unique cases; (3) a facilitated value network, which involves groups of individuals struggling with similar challenges; (4) interconnection between shop, chain and network elements and (5) leadership. We will seek to articulate and assess the value creation model through the work of a community of practice comprised of a diverse international workgroup with representation from executive, financial and clinical leaders as well as other key stakeholders from multiple health systems. We then will conduct pilot studies of a qualitative self-assessment process in participating health systems, and ultimately develop and test quantitative measures for assessing coproduction value creation.

Ethics and dissemination

This study has been approved by the Dartmouth-Hitchcock Health Institutional Review Board (D-HH IRB) as a minimal risk research study. Findings and scholarship will be disseminated broadly through continuous engagement with health system stakeholders, national and international academic presentations and publications and an internet-based electronic platform for publicly accessible study information.
Impact of COPD case finding on clinical care: a prospective analysis of the TargetCOPD trial
Authors: Haroon Shamil , Adab Peymane , Dickens Andrew P , Sitch Alice J , Rai Kiran , Enocson Alexandra , Fitzmaurice David A , Jordan Rachel E
Published: October 2020

Objectives

To investigate the impact of chronic obstructive pulmonary disease (COPD) case finding on clinical care.

Design

We conducted a prospective observational analysis of data from a pragmatic cluster randomised controlled trial in primary care in the West Midlands, UK (TargetCOPD). This compared alternative methods of COPD case finding against usual care. Data were extracted from electronic healthcare records and self-reported questionnaires for a subset of patients with newly diagnosed COPD.

Setting

50 general practices that participated in the TargetCOPD trial.

Participants

Patients aged 40–79 years newly identified with COPD by targeted case finding or by usual care, from 10 August 2012 to 22 June 2014.

Primary and secondary outcome measures

The primary outcome was addition to a COPD register by the end of the trial. The secondary outcome was a clinical care score, derived from the sum of clinical assessments and relevant interventions. Associations between participant characteristics and the primary and secondary outcomes were assessed using multilevel regression.

Results

857 patients identified with COPD by case finding and 764 by usual care were included. Only 21.2% of case-found patients had been added to a COPD register, compared with 92.7% of those diagnosed by usual care. The odds of being added were greater in smokers (adjusted OR 8.68, 95% CI 2.53 to 29.8), and in those with lower percentage of predicted forced expiratory volume in 1 s (adjusted OR 0.96 per percentage rise, 95% CI 0.95 to 0.98). Patients who had been added to a COPD register had a significantly higher clinical care score (mean difference 5.06, 95% CI 4.36 to 5.75).

Conclusions

Only one in five case-found patients had been registered with COPD. Patients added to a COPD register received significantly higher levels of appropriate clinical care.

Trial registration number

ISRCTN14930255; Post-results.
Mixed-method evaluation of CARITAS: a hospital-to-community model of integrated care for dementia
Authors: Ha Ngoc Huong Lien , Chan Ivana , Yap Philip , Nurjono Milawaty , Vrijhoef Hubertus J M , Nicholas Sean Olivia , Wee Shiou-Liang
Published: October 2020

Objectives

The capability and capacity of the primary and community care (PCC) sector for dementia in Singapore may be enhanced through better integration. Through a partnership involving a tertiary hospital and PCC providers, an integrated dementia care network (CARITAS: comprehensive, accessible, responsive, individualised, transdisciplinary, accountable and seamless) was implemented. The study evaluated the process and extent of integration within CARITAS.

Design

Triangulation mixed-methods design and analyses were employed to understand factors underpinning network mechanisms.

Setting

The study was conducted at a tertiary hospital in the northern region of Singapore.

Participants

We recruited participants who were involved in the conceptualisation, design, development and implementation of the CARITAS Programme from a tertiary hospital and PCC providers.

Intervention

We used the Rainbow Model of Integrated Care-Measurement Tool (RMIC-MT) to assess integration from managerial perspectives. RMIC-MT comprises eight dimensions that play interconnected roles on a macro-level, meso-level and micro-level. We administered RMIC-MT to healthcare providers and conducted in-depth interviews with key CARITAS stakeholders.

Primary and secondary outcome measures

We assessed integration scores across eight dimensions of the RMIC-MT and factors underpinning network mechanisms.

Results

Compared with other dimensions, functional integration (mechanisms by which information and management modalities are linked) achieved the lowest mean score of 55. Other dimensions (eg, clinical, professional and organisational integration) scored about 70. Presence of inspiring clinical leaders and tacit interdependencies among partners strengthened the network. However, the lack of structured documentation and a shared information-technology platform hindered functional integration.

Conclusion

CARITAS has reached maturity in micro-levels and meso-levels of integration, while macro-integration needs further development. Integration can be enhanced by assessing service gaps, increasing engagement with stakeholders and providing a shared communication system.
Patient experience studies in the circumpolar region: a scoping review
Authors: Ingemann Christine , Hansen Nathaniel Fox , Hansen Nanna Lund , Jensen Kennedy , Larsen Christina Viskum Lytken , Chatwood Susan
Published: October 2020

Objectives

Patient experiences with health systems constitute a crucial pillar of quality care. Across the Arctic, patients’ interactions with the healthcare system are influenced by challenges of access, historical inequities and social determinants. This scoping review sought to describe the range and nature of peer-reviewed literature on patient experience studies conducted within the circumpolar region.

Design

In a partnership between Danish/Greenlandic, Canadian and American research teams, a scoping review of published research exploring patient experiences in circumpolar regions was undertaken.

Data sources

Seven electronic databases were queried: MEDLINE, Embase, Scopus, ‘Global Health 1910 to 2019 Week 11’, CINAHL, PsycINFO and SveMed+.

Eligibility criteria

Articles were eligible for inclusion if they (a) took place in the circumpolar region, (b) reported patients’ perspective and (c) were focussed primarily on patient experiences with care, rather than satisfaction with treatment outcome.

Data extraction and synthesis

Title and abstract screening, full-text review and data extraction was conducted by four researchers. Bibliometric information such as publication date and country of origin was extracted, as was information regarding study design and whether or not the article contained results relevant to the themes of Indigenous values, rural and remote context, telehealth and climate change. Two researchers then synthesised and characterised results relevant to these themes.

Results

Of the 2824 articles initially found through systematic searches in seven databases, 96 articles were included for data extraction. Findings from the review included unique features related to Indigenous values, rural and remote health, telehealth and climate change.

Conclusions

The review findings provide an overview of patient experiences measures used in circumpolar nations. These findings can be used to inform health system improvement based on patient needs in the circumpolar context, as well as in other regions that share common features. This work can be further contextualized through Indigenous methodologies such as sharing circles and community based participatory methods.
Reliability and reproducibility among different platforms for tumour BRCA testing in ovarian cancer: a study of the Italian NGS Network
Authors: Fumagalli Caterina , Guerini-Rocco Elena , Buttitta Fiamma , Iapicca Pierluigi , You Wenqi , Mauri Michela , Felicioni Lara , Troncone Giancarlo , Malapelle Umberto , Scarpa Aldo , Zamboni Giuseppe , Calistri Daniele , Barberis Massimo , Marchetti Antonio
Published: October 2020

Introduction

BRCA tumour testing is a crucial tool for personalised therapy of patients with ovarian cancer. Since different next-generation sequencing (NGS) platforms and BRCA panels are available, the NGS Italian Network proposed to assess the robustness of different technologies.

Methods

Six centres, using four different technologies, provided raw data of 284 cases, including 75 cases with pathogenic/likely pathogenic variants, for a revision blindly performed by an external bioinformatic platform.

Results

The third-party revision assessed that all the 284 raw data reached good quality parameters. The variant calling analysis confirmed all the 75 pathogenic/likely pathogenic variants, including challenging variants, achieving a concordance rate of 100% regardless of the panel, instrument and bioinformatic pipeline adopted. No additional variants were identified in the reanalysis of a subset of 41 cases.

Conclusions

BRCA tumour testing performed with different technologies in different centres, may achieve the realibility and reproducibility required for clinical diagnostic procedures.
Multimorbidity: the case for prevention
Authors: Head Anna , Fleming Kate , Kypridemos Chris , Pearson-Stuttard Jonathan , O’Flaherty Martin
Published: October 2020

Multimorbidity is of increasing concern for healthcare systems globally, particularly in the context of ageing population structures, such as in the European Union and the UK. Although there is growing attention on developing strategies to manage the health and healthcare burden of older patients with multimorbidity, little research or policy focus has been placed on how to best prevent the development of multimorbidity in future generations. In this research agenda piece, we argue for a shift from a sole focus on the management of multimorbidity in old age to a multimorbidity agenda that considers prevention and management throughout the life-course.
Impact of anatomic site on antigen-presenting cells in cancer
Authors: Zagorulya Maria , Duong Ellen , Spranger Stefani
Published: October 2020

Checkpoint blockade immunotherapy (CBT) can induce long-term clinical benefits in patients with advanced cancer; however, response rates to CBT vary by cancer type. Cancers of the skin, lung, and kidney are largely responsive to CBT, while cancers of the pancreas, ovary, breast, and metastatic lesions to the liver respond poorly. The impact of tissue-resident immune cells on antitumor immunity is an emerging area of investigation. Recent evidence indicates that antitumor immune responses and efficacy of CBT depend on the tissue site of the tumor lesion. As myeloid cells are predominantly tissue-resident and can shape tumor-reactive T cell responses, it is conceivable that tissue-specific differences in their function underlie the tissue-site-dependent variability in CBT responses. Understanding the roles of tissue-specific myeloid cells in antitumor immunity can open new avenues for treatment design. In this review, we discuss the roles of tissue-specific antigen-presenting cells (APCs) in governing antitumor immune responses, with a particular focus on the contributions of tissue-specific dendritic cells. Using the framework of the Cancer-Immunity Cycle, we examine the contributions of tissue-specific APC in CBT-sensitive and CBT-resistant carcinomas, highlight how these cells can be therapeutically modulated, and identify gaps in knowledge that remain to be addressed.
In situ decellularization of a large animal saccular aneurysm model: sustained inflammation and active aneurysm wall remodeling
Authors: King Robert M , Caroff Jildaz , Langan Erin T , Leporati Anita , Rodriguez-Rodriguez Aurora , Raskett Christopher M , Gupta Suresh , Puri Ajit S , Caravan Peter , Gounis Matthew J , Bogdanov, Jr. Alexei A
Published: October 2020

Objective

To investigate in situ decellularization of a large animal model of saccular aneurysm as a strategy for achieving aneurysmal growth and lasting inflammation.

Methods

18 New Zealand White rabbits were randomized 2:1 to receive endoluminal sodium dodecyl sulfate infusion (SDS, 1% solution, 45 min) following elastase or elastase-only treatment (control). All aneurysms were measured by digital subtraction angiography every 2 weeks. Every 2 weeks, three of the rabbits (two elastase + SDS, one control) underwent MRI, followed by contrast injection with myeloperoxidase (MPO)-sensing contrast agent. MRI was repeated 3 hours after contrast injection and the enhancement ratio (ER) was calculated. Following MRI, aneurysms were explanted and subjected to immunohistopathology.

Results

During follow-up MRI, the average ER for SDS-treated animals was 1.63±0.20, compared with 1.01±0.06 for controls (p<0.001). The width of SDS-treated aneurysms increased significantly in comparison with the elastase aneurysms (47% vs 20%, p<0.001). Image analysis of thin sections showed infiltration of MPO-positive cells in decellularized aneurysms and surroundings through the 12-week observation period while control tissue had 5–6 times fewer cells present 2 weeks after aneurysm creation. Immunohistochemistry demonstrated the presence of MPO-positive cells surrounding decellularized lesions at early time points. MPO-positive cells were found in the adventitia and in the thrombi adherent to the aneurysm wall at later time points.

Conclusions

In situ decellularization of a large animal model of saccular aneurysms reproduces features of unstable aneurysms, such as chronic inflammation (up to 12 weeks) and active aneurysm wall remodeling, leading to continued growth over 8 weeks.
Hemodynamics in aneurysm blebs with different wall characteristics
Authors: Salimi Ashkezari Seyedeh Fatemeh , Mut Fernando , Chung Bong Jae , Yu Alexander K , Stapleton Christopher J , See Alfred P , Amin-Hanjani Sepideh , Charbel Fady T , Rezai Jahromi Behnam , Niemelä Mika , Frösen Juhana , Maiti Spandan , Robertson Anne M , Cebral Juan R
Published: October 2020

Background

Blebs are important secondary structures of intracranial aneurysms associated with increased rupture risk and can affect local wall stress and hemodynamics. Mechanisms of bleb development and evolution are not clearly understood. We investigate the relationship between blebs with different wall characteristics and local hemodynamics and rupture sites.

Methods

Blebs with different wall appearances in intra-operative videos were analyzed with image-based computational fluid dynamics. Thin red blebs were compared against thick atherosclerotic/hyperplastic white/yellow blebs. Rupture points were identified in videos of ruptured aneurysms harboring blebs.

Results

Thin blebs tended to be closer to the inflow than atherosclerotic blebs of the same aneurysm (P=0.0234). Blebs near the inflow had higher velocity (P=0.0213), vorticity (P=0.0057), shear strain rate (P=0.0084), wall shear stress (WSS) (P=0.0085), and WSS gradient (P=0.0151) than blebs far from the inflow. In a subset of 12 ruptured aneurysms harboring blebs, rupture points were associated with thin blebs in 42% of aneurysms, atherosclerotic blebs in 25%, and were away from blebs in the remaining 33%.

Conclusions

Not all blebs are equal; some have thin translucent walls while others have thick atherosclerotic walls. Thin blebs tend to be located closer to the inflow than atherosclerotic blebs. Blebs near the inflow are exposed to stronger flows with higher and spatially variable WSS than blebs far from the inflow which tend to have uniformly lower WSS. Aneurysms can rupture at thin blebs, atherosclerotic blebs, and even away from blebs. Further study of wall failure in aneurysms with different bleb types is needed.
Effective action from the functional renormalization group
Authors: Ohta Nobuyoshi , Rachwał Lesław
Published: October 2020

We study the quantum gravitational system coupled to a charged scalar, Dirac fermions, and electromagnetic fields. We use the “exact” or “functional” renormalization group equation to derive the effective action $$\Gamma _0$$

Γ
0

by integrating the flow equation from the ultraviolet scale down to $$k=0$$

k
=
0

. The resulting effective action consists of local terms and nonlocal terms with unique coefficients.
Projection for Büchi Tree Automata with Constraints between Siblings
Authors: Landwehr Patrick , Löding Christof
Published: October 2020

We consider an extension of tree automata on infinite trees that can use equality and disequality constraints between direct subtrees of a node. Recently, it has been shown that the emptiness problem for these kind of automata with a parity acceptance condition is decidable and that the corresponding class of languages is closed under Boolean operations. In this paper, we show that the class of languages recognizable by such tree automata with a Büchi acceptance condition is closed under projection. This construction yields a new algorithm for the emptiness problem, implies that a regular tree is accepted if the language is non-empty (for the Büchi condition), and can be used to obtain a decision procedure for an extension of monadic second-order logic with predicates for subtree comparisons.
Inverse Problem in the Kuramoto Model with a Phase Lag: Application to the Sun
Authors: Blanter Elena , Shnirman Mikhail
Published: October 2020

We solve the inverse problem in the Kuramoto model with three nonidentical oscillators and a phase lag. The model represents a three-cell-in-depth radial profile of the solar meridional circulation in each solar hemisphere and describes the synchronization between the two components (toroidal and poloidal) of the solar magnetic field. We reconstruct natural frequencies of the top and the bottom oscillators from the evolution of their phases when the oscillators are phase-locked. The phase-locking allows to solve the inverse problem when the phase of the middle oscillator is not available. We present the exact solution and investigate its stability. The model reveals a crucial role of the phase lag in the inverse problem solution. We apply the model to the reconstruction of the deep meridional circulation of the Sun and discuss peculiarities of its evolution in terms of solar dynamo.