bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are Phage Lytic Proteins the Secret Weapon To Kill
Staphylococcus aureus
?
Authors: Gutiérrez Diana , Fernández Lucía , Rodríguez Ana , García Pilar 
Published: January 2018

ABSTRACT

Methicillin-resistant
Staphylococcus aureus
(MRSA) is one of the most threatening microorganisms for global human health. The current strategies to reduce the impact of
S. aureus
include a restrictive control of worldwide antibiotic use, prophylactic measures to hinder contamination, and the search for novel antimicrobials to treat human and animal infections caused by this bacterium. The last strategy is currently the focus of considerable research. In this regard, phage lytic proteins (endolysins and virion-associated peptidoglycan hydrolases [VAPGHs]) have been proposed as suitable candidates. Indeed, these proteins display narrow-spectrum antimicrobial activity and a virtual lack of bacterial-resistance development. Additionally, the therapeutic use of phage lytic proteins in
S. aureus
animal infection models is yielding promising results, showing good efficacy without apparent side effects. Nonetheless, human clinical trials are still in progress, and data are not available yet. This minireview also analyzes the main obstacles for introducing phage lytic proteins as human therapeutics against
S. aureus
infections. Besides the common technological problems derived from large-scale production of therapeutic proteins, a major setback is the lack of a proper legal framework regulating their use. In that sense, the relevant health authorities should urgently have a timely discussion about these new antimicrobials. On the other hand, the research community should provide data to dispel any doubts regarding their efficacy and safety. Overall, the appropriate scientific data and regulatory framework will encourage pharmaceutical companies to invest in these promising antimicrobials.
Adaptive Evolution of RH5 in Ape
Plasmodium
species of the
Laverania
Subgenus
Authors: Plenderleith Lindsey J. , Liu Weimin , MacLean Oscar A. , Li Yingying , Loy Dorothy E. , Sundararaman Sesh A. , Bibollet-Ruche Frederic , Learn Gerald H. , Hahn Beatrice H. , Sharp Paul M. 
Published: January 2018

ABSTRACT

Plasmodium falciparum
, the major cause of malaria morbidity and mortality in humans, has been shown to have emerged after cross-species transmission of one of six host-specific parasites (subgenus
Laverania
) infecting wild chimpanzees (
Pan troglodytes
) and western gorillas (
Gorilla gorilla
). Binding of the parasite-encoded ligand RH5 to the host protein basigin is essential for erythrocyte invasion and has been implicated in host specificity. A recent study claimed to have found two amino acid changes in RH5 that “drove the host shift leading to the emergence of
P. falciparum
as a human pathogen.” However, the ape
Laverania
data available at that time, which included only a single distantly related chimpanzee parasite sequence, were inadequate to justify any such conclusion. Here, we have investigated
Laverania Rh5
gene evolution using sequences from all six ape parasite species. Searching for gene-wide episodic selection across the entire
Laverania
phylogeny, we found eight codons to be under positive selection, including three that correspond to contact residues known to form hydrogen bonds between
P. falciparum
RH5 and human basigin. One of these sites (residue 197) has changed subsequent to the transmission from apes to humans that gave rise to
P. falciparum
, suggesting a possible role in the adaptation of the gorilla parasite to the human host. We also found evidence that the patterns of nucleotide polymorphisms in
P. falciparum
are not typical of
Laverania
species and likely reflect the recent demographic history of the human parasite.

IMPORTANCE
A number of closely related, host-specific malaria parasites infecting wild chimpanzees and gorillas have recently been described. The most important cause of human malaria,
Plasmodium falciparum
, is now known to have resulted from a cross-species transmission of one of the gorilla parasites. Overcoming species-specific interactions between a parasite ligand, RH5, and its receptor on host cells, basigin, was likely an important step in the origin of the human parasite. We have investigated the evolution of the
Rh5
gene and found evidence of adaptive changes during the diversification of the ape parasite species at sites that are known to form bonds with human basigin. One of these changes occurred at the origin of
P. falciparum
, implicating it as an important adaptation to the human host.
Identifying patients at risk of inhospital death or hospice transfer for early goals of care discussions in a US referral center: the HELPS model derived from retrospective data
Authors: Romero-Brufau Santiago , Whitford Daniel , Whitford Kevin J , Manning Dennis M , Huddleston Jeanne M 
Published: January 2018

ObjectiveCreate a score to identify patients at risk of death or hospice placement who may benefit from goals of care discussion earlier in the hospitalisation.DesignRetrospective cohort study to develop a risk index using multivariable logistic regression.SettingTwo tertiary care hospitals in Southeastern Minnesota.Participants92 879 adult general care admissions (50% male, average age 60 years).Primary and secondary outcome measuresOur outcome measure was an aggregate of inhospital death or discharge to hospice. Predictor variables for the model encompassed comorbidities, nutrition status, functional status, demographics, fall risk, mental status, Charlson Comorbidity Index and acuity of illness on admission. Resuscitation status, race, geographic area of residence and marital status were added as covariates to account for confounding.ResultsInhospital mortality and discharge to hospice were rare, with incidences of 1.2% and 0.8%, respectively. The Hospital End-of-Life Prognostic Score (HELPS) demonstrated good discrimination (C-statistic=0.866 in derivation set and 0.834 in validation set). The patients with the highest 5% of scores had an 8% risk of the outcome measure, relative risk 12.9 (10.9–15.4) when compared to the bottom 95%.ConclusionsHELPS is able to identify patients with a high risk of inhospital death or need for hospice at discharge. These patients may benefit from early goals of care discussions.
Evaluating dengue burden in Africa in passive fever surveillance and seroprevalence studies: protocol of field studies of the Dengue Vaccine Initiative
Authors: Lim Jacqueline Kyungah , Carabali Mabel , Lee Jung-Seok , Lee Kang-Sung , Namkung Suk , Lim Sl-Ki , Ridde Valéry , Fernandes Jose , Lell Bertrand , Matendechero Sultani Hadley , Esen Meral , Andia Esther , Oyembo Noah , Barro Ahmed , Bonnet Emmanuel , Njenga Sammy M , Agnandji Selidji Todagbe , Yaro Seydou , Alexander Neal , Yoon In-Kyu 
Published: January 2018

IntroductionDengue is an important and well-documented public health problem in the Asia-Pacific and Latin American regions. However, in Africa, information on disease burden is limited to case reports and reports of sporadic outbreaks, thus hindering the implementation of public health actions for disease control. To gather evidence on the undocumented burden of dengue in Africa, epidemiological studies with standardised methods were launched in three locations in Africa.Methods and analysisIn 2014–2017, the Dengue Vaccine Initiative initiated field studies at three sites in Ouagadougou, Burkina Faso; Lambaréné, Gabon and Mombasa, Kenya to obtain comparable incidence data on dengue and assess its burden through standardised hospital-based surveillance and community-based serological methods. Multidisciplinary measurements of the burden of dengue were obtained through field studies that included passive facility-based fever surveillance, cost-of-illness surveys, serological surveys and healthcare utilisation surveys. All three sites conducted case detection using standardised procedures with uniform laboratory assays to diagnose dengue. Healthcare utilisation surveys were conducted to adjust population denominators in incidence calculations for differing healthcare seeking patterns. The fever surveillance data will allow calculation of age-specific incidence rates and comparison of symptomatic presentation between patients with dengue and non-dengue using multivariable logistic regression. Serological surveys assessed changes in immune status of cohorts of approximately 3000 randomly selected residents at each site at 6-month intervals. The age-stratified serosurvey data will allow calculation of seroprevalence and force of infection of dengue. Cost-of-illness evaluations were conducted among patients with acute dengue by Rapid Diagnostic Test.Ethics and disseminationBy standardising methods to evaluate dengue burden across several sites in Africa, these studies will generate evidence for dengue burden in Africa and data will be disseminated as publication in peer-review journals in 2018.
‘I did try and point out about his dignity’: a qualitative narrative study of patients and carers’ experiences and expectations of junior doctors
Authors: Kostov Camille E , Rees Charlotte E , Gormley Gerard J , Monrouxe Lynn V 
Published: January 2018

ObjectivesFor many years, the voice of patients has been understood as a critical element for the improvement of care quality in healthcare settings. How well medical graduates are prepared for clinical practice is an important question, but one that has rarely been considered from patient and public perspectives. We aimed to fill this gap by exploring patients and carers’ experiences and expectations of junior doctors.DesignThis comprises part of a wider study on UK medical graduates’ preparedness for practice. A qualitative narrative methodology was used, comprising four individual and six group interviews.Participants25 patients and carers from three UK countries.AnalysisData were transcribed, anonymised and analysed using framework analysis.Main resultsWe identified three themes pertinent to answering our research question: (1) sources of knowledge (sources of information contributing to patients and carers’ perceptions of junior doctors’ impacting on expectations); (2) desires for student/trainee learning (experiences and expectations of medical training); and (3) future doctors (experiences and expectations of junior doctors). We also highlight metaphorical talk and humour, where relevant, in the quotes presented to give deeper insights into participants’ perspectives of the issues. Participants focused on personal and interpersonal aspects of being a doctor, such as respect and communication. There was a strong assertion that medical graduates needed to gain direct experience with a diverse range of patients to encourage individualised care. Participants narrated their experiences of having symptoms ignored and attributed to an existing diagnosis (‘diagnostic overshadowing’) and problems relating to confidentiality.ConclusionsOur findings support the view that patients and carers have clear expectations about junior doctors, and that patient views are important for preparing junior doctors for practice. There is a necessity for greater dialogue between patients, doctors and educators to clarify expectations and confidentiality issues around patient care.
Study protocol for One Health data collections, analyses and intervention of the Sino-Swedish integrated multisectoral partnership for antibiotic resistance containment (IMPACT)
Authors: Sun Qiang , Wang Yang , Hulth Anette , Xiao Yonghong , Nilsson Lennart E , Li Xuewen , Bi Zhenwang , Liu Yuqing , Yin Hong , Luo Yanbo , Nilsson Maud , Sun Chengtao , Zhu Yiqing , Zheng Beiwen , Chen Baoli , Sun Pan , Ding Lilu , Xia Xi , Ottoson Jakob , Löfmark Sonja , Dyar Oliver James , Börjesson Stefan , Lundborg Cecilia Stalsby 
Published: January 2018

IntroductionTo effectively minimise the emergence and dissemination of antibiotic resistant bacteria, a holistic One Health approach is called for. The Sino-Swedish Integrated Multisectoral Partnership for Antibiotic Resistance Containment is a cross-sectoral and integrated project on antibiotic resistance, conducted in Shandong Province in China. This paper outlines the overall study protocol for the project. To our knowledge, this is the first research programme aiming to take a true holistic approach across multiple sectors simultaneously in China, and the first to incorporate both antibiotic use and infection prevention and control in addition to antibiotic resistance patterns. The project aims to address gaps in current knowledge and seeks to improve the situation through a system-wide intervention. By using a One Health approach we can address important research questions that individual discipline investigations are unable to. The results obtained should thus more closely reflect the world in which human health, animal health and the environment are inextricably and intimately interlinked.Methods and analysisBoth quantitative and qualitative studies are included for households from 12 villages, their surrounding environment and a tertiary care hospital in a nearby town. The studies include analyses of antibiotic consumption for humans and pigs; qualitative and quantitative data on perceptions, knowledge and attitudes; faecal carriage of extended spectrum β-lactamase and carbapenemase-producingEnterobacteriaceaefrom pigs and humans, and occurrence in household drinking water, surface water, waste water and clinical bacterial isolates from the hospital. Carriage of methicillin-resistantStaphylococcus aureusin humans, household pigs and clinical bacterial isolates is also investigated. Furthermore, potential inter-relationships between these sources are analysed. A multifaceted One Health intervention is designed and implemented in 6 of the 12 villages. Repeated and continuous data collections take place over 2 years, where the repeated data collection is performed after 1 year of intervention. Comparisons are made between intervention and control villages, before and after the intervention.EthicsEthics approval was obtained from the first Affiliated Hospital, College of Medicine, Zhejiang University, China, reference number 2015#185 and 2015#283.
Qualitative findings on building a partnered approach to implementation of a group-based diabetes intervention in VA primary care
Authors: Arney Jennifer , Thurman Kimberly , Jones Lindsey , Kiefer Lea , Hundt Natalie E , Naik Aanand D , Woodard LeChauncy D 
Published: January 2018

ObjectiveConduct a formative evaluation to inform the implementation of ‘Empowering Patients in Chronic Care’ (EPIC), an evidence-based interdisciplinary group medical appointment intervention to improve collaborative goal-setting in patients with treated but uncontrolled diabetes.DesignThe formative evaluation involved qualitative, in-depth interviews with clinicians, structured according to the Promoting Action on Research in Health Services framework. Interviews elicited (1) participants’ knowledge regarding interdisciplinary group self-management and goal-setting programmes and how well clinicians embrace these interventions (evidence), (2) physical and social climate at each target facility and how the intervention can best be embedded into routine primary care (context) and (3) site-specific needs to be addressed by our implementation team and clinicians’ preparedness and intentions to participate in the intervention (facilitation).SettingClinicians were part of a primary care setting at one of five participating medical facilities within one Veterans Health Administration Veterans Affairs regional network.ParticipantsWe interviewed a snowball sample of 35 interdisciplinary clinicians engaged in diabetes management, practising leadership and administrators at target sites.ResultsMost participants had previous experience with diabetes group self-management programmes and viewed group appointments as an effective approach to enhancing care. Discussions about existing group appointments provided a context for evaluating potential barriers and facilitators to implementing EPIC into target sites. Interviews revealed clinicians’ expectations about the roles they would play in the intervention, their assessments of the roles and strategies to facilitate their performance in those roles.ConclusionsSuccessful implementation of evidence-based practices into routine care requires a partnered approach with engaged local staff. The intervention should address local goals and research objectives to encourage bidirectional engagement. Robust partnerships are nurtured further by sustained, open communication and must consider the context, target population and local experience to address barriers and facilitators to implementation.
The Suspected CANcer (SCAN) pathway: protocol for evaluating a new standard of care for patients with non-specific symptoms of cancer
Authors: Nicholson Brian D , Oke Jason , Friedemann Smith Claire , Phillips Julie-Ann , Lee Jennifer , Abel Lucy , Kelly Sadie , Gould Isabella , Mackay Toni , Kaveney Zoe , Anthony Suzie , Hayles Shelley , Lasserson Daniel , Gleeson Fergus 
Published: January 2018

IntroductionCancer survival in England lags behind most European countries, due partly to lower rates of early stage diagnosis. We report the protocol for the evaluation of a multidisciplinary diagnostic centre-based pathway for the investigation of ‘low-risk but not no-risk’ cancer symptoms called the Suspected CANcer (SCAN) pathway. SCAN is a new standard of care being implemented in Oxfordshire; one of a number of pathways implemented during the second wave of the Accelerate, Coordinate, Evaluate (ACE) programme, an initiative which aims to improve England’s cancer survival rates through establishing effective routes to early diagnosis.Methods and analysisTo evaluate SCAN, we are collating a prospective database of patients referred onto the pathway by their general practitioner (GP). Patients aged over 40 years, with non-specific symptoms such as weight loss or fatigue, who do not meet urgent cancer referral criteria or for whom symptom causation remains unclear after investigation via other existing pathways, can be referred to SCAN. SCAN provides rapid CT scanning, laboratory testing and clinic review within 2 weeks. We will follow all patients in the primary and secondary care record for at least 2 years. The data will be used to understand the diagnostic yield of the SCAN pathway in the short term (28 days) and the long term (2 years). Routinely collected primary and secondary care data from patients not referred to SCAN but with similar symptoms will also be used to evaluate SCAN. We will map the routes to diagnosis for patients referred to SCAN to assess cost-effectiveness. Acceptability will be evaluated using patient and GP surveys.Ethics and disseminationThe Oxford Joint Research Office Study Classification Group has judged this to be a service evaluation and so outside of research governance. The results of this project will be disseminated by peer-reviewed publication and presentation at conferences.
Time trends in peripheral artery disease incidence, prevalence and secondary preventive therapy: a cohort study in The Health Improvement Network in the UK
Authors: Cea-Soriano Lucía , Fowkes F Gerry R , Johansson Saga , Allum Alaster M , García Rodriguez Luis Alberto 
Published: January 2018

ObjectivesTo assess time trends in symptomatic peripheral artery disease (PAD) incidence and prevalence, and secondary preventive therapy.DesignCohort study using The Health Improvement Network.SettingUK primary care.ParticipantsIndividuals aged 50–89 years identified annually between 2000 and 2014. Participants with symptomatic PAD were identified using Read codes.Outcome measuresIncidence and prevalence of symptomatic PAD from 2000 to 2014, overall and by sex and age. Proportion of patients prescribed secondary preventive therapy with acetylsalicylic acid (ASA), clopidogrel, an ACE inhibitor, an angiotensin receptor blocker (ARB) and/or a statin.ResultsThe incidence of symptomatic PAD per 10 000 person-years decreased over time, from 38.6 (men: 51.0; women: 28.7) in 2000 to 17.3 (men: 23.1; women: 12.4) in 2014. The prevalence of symptomatic PAD decreased from 3.4% (men: 4.5%; women: 2.5%) in 2000 to 2.4% (men: 3.1%; women: 1.7%) in 2014. Incidence and prevalence decreases were observed in all age groups. The proportions of patients prescribed ASA monotherapy, clopidogrel monotherapy and dual antiplatelet therapy in the 2 months after PAD diagnosis were 42.7%, 2.9% and 2.5%, respectively, during 2000–2003, and 44.7%, 11.0% and 5.2%, respectively, during 2012–2014. For ACE inhibitor/ARB therapy and statins, proportions in the 2 months after diagnosis were 30.2% and 31.2%, respectively, during 2000–2003, and 45.1% and 65.9%, respectively, during 2012–2014.ConclusionThe incidence and prevalence of symptomatic PAD diagnosed in UK primary care are decreasing. A large proportion of the population with PAD in clinical practice does not receive guideline-recommended secondary prevention therapy.
Incidence and mortality of fractures by frailty level over 80 years of age: cohort study using UK electronic health records
Authors: Ravindrarajah Rathi , Hazra Nisha C , Charlton Judith , Jackson Stephen H D , Dregan Alex , Gulliford Martin C 
Published: January 2018

ObjectiveThis study aimed to estimate the association of frailty with incidence and mortality of fractures at different sites in people aged over 80 years.DesignCohort study.SettingUK family practices from 2001 to 2014.Participants265 195 registered participants aged 80 years and older.MeasurementsFrailty status classified into ‘fit’, ‘mild’, ‘moderate’ and ‘severe’ frailty. Fractures, classified into non-fragility and fragility, including fractures of femur, pelvis, shoulder and upper arm, and forearm/wrist. Incidence of fracture, and mortality within 90 days and 1 year, were estimated.ResultsThere were 28 643 fractures including: non-fragility fractures, 9101; femur, 12 501; pelvis, 2172; shoulder and upper arm, 4965; and forearm/wrist, 6315. The incidence of each fracture type was higher in women and increased with frailty category (femur, severe frailty compared with ‘fit’, incidence rate ratio (IRR) 2.4, 95% CI 2.3 to 2.6). Fractures of the femur (95–99 years compared with 80–84 years, IRR 2.7, 95% CI 2.6 to 2.9) and pelvis (IRR 2.9, 95% CI 2.5 to 3.3) were strongly associated with age but non-fragility and forearm fractures were not. Mortality within 90 days was greatest for femur fracture (adjusted HR, compared with forearm fracture 4.3, 95% CI 3.7 to 5.1). Mortality was higher in men and increased with age (HR 5.3, 95% CI 4.3 to 6.5 in those over 100 years compared with 80–84 years) but was less strongly associated with frailty category. Similar associations with fractures were seen at 1-year mortality.ConclusionsThe incidence of fractures at all sites was higher in women and strongly associated with advancing frailty status, while the risk of mortality after a fracture was greater in men and was associated with age rather than frailty category.