bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a Human Respiratory Syncytial Virus Cell Entry Inhibitor by Using a Novel Lentiviral Pseudotype System
Authors: Haid Sibylle , Grethe Christina , Bankwitz Dorothea , Grunwald Thomas , Pietschmann Thomas 
Published: December 2015

ABSTRACT

Lentiviral budding is governed by group-specific antigens (Gag proteins) and proceeds in the absence of cognate viral envelope proteins, which has been exploited to create pseudotypes incorporating envelope proteins from nonlentiviral families. Here, we report the generation of infectious lentiviral pseudoparticles incorporating human respiratory syncytial virus (hRSV) F protein alone (hRSV-Fpp) or carrying SH, G, and F proteins (hRSV-SH/G/Fpp). These particles recapitulate key infection steps of authentic hRSV particles, including utilization of glycosaminoglycans and low-pH-independent cell entry. Moreover, hRSV pseudoparticles (hRSVpp) can faithfully reproduce phenotypic resistance to a small-molecule fusion inhibitor in clinical development (BMS-433771) and a licensed therapeutic F protein-targeting antibody (palivizumab). Inoculation of several human cell lines from lung and liver revealed more than 30-fold differences in susceptibility to hRSVpp infection, suggesting differential expression of hRSV entry cofactors and/or restriction factors between these cell types. Moreover, we observed cell-type-dependent functional differences between hRSVpp carrying solely F protein or SH, G, and F proteins with regard to utilization of glycosaminoglycans. Using hRSVpp, we identified penta-
O
-galloyl-β-
d
-glucose (PGG) as a novel hRSV cell entry inhibitor. Moreover, we show that PGG also inhibits cell entry of hRSVpp carrying F proteins resistant to BMS-433771 or palivizumab. This work sheds new light on the mechanisms of hRSV cell entry, including possible strategies for antiviral intervention. Moreover, hRSVpp should prove valuable to dissect hRSV envelope protein functions, including the interaction with cell entry factors.

IMPORTANCE
Lentiviral pseudotypes are highly useful to specifically dissect the functions of viral and host factors in cell entry, which have been exploited for numerous viruses. Here, we successfully created hRSVpp and show that they faithfully recapitulate key characteristics of parental hRSV cell entry. Importantly, hRSVpp accurately mirror hRSV resistance to small-molecule fusion inhibitors and clinically approved therapeutic antibodies. Moreover, we observed highly different susceptibilities of cell lines to hRSVpp infection and also differences between hRSVpp types (with F protein alone or with SH, G, and F proteins) in regard to cell entry. This indicates differential expression of host factors determining hRSV cell entry between these cell lines and highlights the fact that the hRSVpp system is useful to explore the functional properties of hRSV envelope protein combinations. Therefore, this system will be highly useful to study hRSV cell entry and host factor usage and to explore antiviral strategies targeting hRSV cell entry.
Supporting decisions to increase the safe discharge of children with febrile illness from the emergency department: a systematic review and meta-analysis
Authors: Irwin A D , Wickenden J , Le Doare K , Ladhani S , Sharland M 
Published: December 2015

BackgroundDespite fewer serious infections presenting to the children's emergency department (ED), hospital admissions of children with febrile illness have increased. We review evidence for the use of decision rules to increase the safe discharge of these children from the ED.MethodsA systematic review of prospective studies of decision rules for the discharge of children with febrile illness, and prediction rules for the diagnosis of serious infections in children presenting to ED. We reviewed the MEDLINE database, Cochrane Library and hand searched the bibliographies of related studies. The search was limited to the English language.ResultsThirty-three studies were identified. Fourteen reported low-risk criteria to rule out serious bacterial infection (SBI) in infants less than 3 months of age. In this group, clinical tools such as the Rochester and Philadelphia criteria support the safe discharge of low-risk infants without empirical antibiotics. Seventeen studies reported prediction rules in older children, though only four included children over 3 years. Two impact studies based upon multivariable prediction models failed to demonstrate any impact on rates of discharge from ED.ConclusionsThe use of clinical prediction models can improve discrimination between serious and self-limiting infections in children. The application of low-risk thresholds may help to rule out serious infections and discharge children from the ED without empirical antibiotics. A growing evidence base for prediction rules has so far failed to translate into validated rules to aid decision-making. Future work should evaluate decision rules in well designed impact studies, focusing on the need for hospital admission and antibiotic therapy.
The psychological response to injury in student athletes: a narrative review with a focus on mental health
Authors: Putukian Margot 
Published: December 2015

BackgroundInjury is a major stressor for athletes and one that can pose significant challenges. Student athletes must handle rigorous academic as well as athletic demands that require time as well as significant physical requirements. Trying to perform and succeed in the classroom and on the playing field has become more difficult as the demands and expectations have increased. If an athlete is injured, these stressors increase.Main thesisStress is an important antecedent to injuries and can play a role in the response to, rehabilitation and return to play after injury. The psychological response to injury can trigger and/or unmask mental health issues including depression and suicidal ideation, anxiety, disordered eating, and substance use/abuse. There are barriers to mental health treatment in athletes. They often consider seeking help as a sign of weakness, feeling that they should be able to ‘push through’ psychological obstacles as they do physical ones. Athletes may not have developed healthy coping behaviours making response to injury especially challenging.PurposeI discuss the current state of knowledge regarding the psychological response to injury and delineate resources necessary to direct the injured athlete to a mental health care provider if appropriate.
Starting antidepressant use: a qualitative synthesis of UK and Australian data
Authors: Anderson Claire , Kirkpatrick Susan , Ridge Damien , Kokanovic Renata , Tanner Claire 
Published: December 2015

ObjectiveTo explore people's experiences of starting antidepressant treatment.DesignQualitative interpretive approach combining thematic analysis with constant comparison. Relevant coding reports from the original studies (generated using NVivo) relating to initial experiences of antidepressants were explored in further detail, focusing on the ways in which participants discussed their experiences of taking or being prescribed an antidepressant for the first time.Participants108 men and women aged 22–84 who had taken antidepressants for depression.SettingRespondents recruited throughout the UK during 2003–2004 and 2008 and 2012–2013 and in Australia during 2010–2011.ResultsPeople expressed a wide range of feelings about initiating antidepressant use. People's attitudes towards starting antidepressant use were shaped by stereotypes and stigmas related to perceived drug dependency and potentially extreme side effects. Anxieties were expressed about starting use, and about how long the antidepressant might begin to take effect, how much it might help or hinder them, and about what to expect in the initial weeks. People worried about the possibility of experiencing adverse effects and implications for their senses of self. Where people felt they had not been given sufficient time during their consultation information or support to take the medicines, the uncertainty could be particularly unsettling and impact on their ongoing views on and use of antidepressants as a viable treatment option.ConclusionsOur paper is the first to explore in-depth patient existential concerns about start of antidepressant use using multicountry data. People need additional support when they make decisions about starting antidepressants. Health professionals can use our findings to better understand and explore with patients’ their concerns before their patients start antidepressants. These insights are key to supporting patients, many of whom feel intimidated by the prospect of taking antidepressants, especially during the uncertain first few weeks of treatment.
Research is ‘a step into the unknown’: an exploration of pharmacists’ perceptions of factors impacting on research participation in the NHS
Authors: Lowrie Richard , Morrison Graeme , Lees Rosalind , Grant Christopher H , Johnson Chris , MacLean Fiona , Semple Yvonne , Thomson Alison , Harrison Heather , Mullen Alexander B , Lannigan Norman , Macdonald Sara 
Published: December 2015

ObjectiveThis study explored National Health Service (NHS) pharmacists’ perceptions and experiences of pharmacist-led research in the workplace.DesignSemistructured, face-to-face discussions continued until distinct clusters of opinion characteristics formed. Verbatim transcripts of audio-recordings were subjected to framework analysis.SettingInterviews were carried out with 54 pharmacists with diverse backgrounds and roles from general practices and secondary care in the UK's largest health authority.ResultsThe purpose and potential of health services research (HSR) was understood and acknowledged to be worthwhile by participants, but a combination of individual and system-related themes tended to make participation difficult, except when this was part of formal postgraduate education leading to a qualification. Lack of prioritisation was routinely cited as the greatest barrier, with motivation, confidence and competence as additional impediments. System-related themes included lack of practical support and pharmacy professional issues. A minority of highly motivated individuals managed to embed research participation into routine activity.ConclusionsMost pharmacists realised the desirability and necessity of research to underpin pharmacy service expansion, but a combination of individual and professional level changes is needed to increase activity. Our findings provide a starting point for better understanding the mindset of hospital-based and general practice-based pharmacists towards research, as well as their perceived barriers and supports.
Long-term efficacy and safety of incobotulinumtoxinA and conventional treatment of poststroke arm spasticity: a prospective, non-interventional, open-label, parallel-group study
Authors: Dressler Dirk , Rychlik Reinhard , Kreimendahl Fabian , Schnur Nicole , Lambert-Baumann Judith 
Published: December 2015

ObjectiveTo compare the efficacy and safety of incobotulinumtoxinA with conventional antispastic therapy for poststroke arm spasticity in routine clinical practice over a 1-year period.DesignProspective, non-interventional, open-label, parallel-group study.Setting47 centres in Germany.ParticipantsPatients with poststroke arm spasticity; 108 receiving incobotulinumtoxinA, 110 conventional therapy.InterventionConventional antispastic treatment including oral antispastic medications, physiotherapy and occupational therapy or 3-monthly incobotulinumtoxinA injections plus conventional therapy if required.Main outcome measuresThe main outcome measure was changes in muscle tone (Ashworth Scale) over the 1-year treatment period. Changes in functional disability (Disability Assessment Scale) and quality of life (Short-Form-12 Health Survey) were additionally assessed. Ratings for therapy outcome (Goal Attainment Scale), and efficacy and tolerability of treatment (Global Clinical Impression Scale) were also obtained.ResultsMuscle tone improved for all spasticity patterns with the Ashworth Scale responder rates between 63% and 86% (incobotulinumtoxinA) and 16–27% (conventional therapy). Median improvement in functional disability was –1.0 (incobotulinumtoxinA) and 0.0 (conventional measures) for all domains. Treatment goals were attained by 93% of incobotulinumtoxinA patients and 30% of patients under conventional therapy. Most physicians (93%) and patients (90%) rated efficacy as good or very good under incobotulinumtoxinA; the proportions were much lower under conventional therapy (36% and 37%). Tolerability under incobotulinumtoxinA was considered good or very good by 99% of physicians and patients (76% and 66%, respectively, under conventional therapy). Quality of life under incobotulinumtoxinA improved by 8.0 (physical score) and 10.8 (mental score) and by 0.8 and 5.7, respectively, under conventional therapy.ConclusionsIncobotulinumtoxinA combined with rehabilitation and oral medication produces a much more robust improvement in all aspects of arm spasticity than conventional antispastic treatment. Effects are stable over a period of 1 year, whereas adverse effects are negligible. IncobotulinumtoxinA should be considered the treatment of choice for poststroke arm spasticity.
Patient satisfaction and perceived quality of care: evidence from a cross-sectional national exit survey of HIV and non-HIV service users in Zambia
Authors: Dansereau Emily , Masiye Felix , Gakidou Emmanuela , Masters Samuel H , Burstein Roy , Kumar Santosh 
Published: December 2015

ObjectiveTo examine the associations between perceived quality of care and patient satisfaction among HIV and non-HIV patients in Zambia.SettingPatient exit survey conducted at 104 primary, secondary and tertiary health clinics across 16 Zambian districts.Participants2789 exiting patients.Primary independent variablesFive dimensions of perceived quality of care (health personnel practice and conduct, adequacy of resources and services, healthcare delivery, accessibility of care, and cost of care).Secondary independent variablesRespondent, visit-related, and facility characteristics.Primary outcome measurePatient satisfaction measured on a 1–10 scale.MethodsIndices of perceived quality of care were modelled using principal component analysis. Statistical associations between perceived quality of care and patient satisfaction were examined using random-effect ordered logistic regression models, adjusting for demographic, socioeconomic, visit and facility characteristics.ResultsAverage satisfaction was 6.9 on a 10-point scale for non-HIV services and 7.3 for HIV services. Favourable perceptions of health personnel conduct were associated with higher odds of overall satisfaction for non-HIV (OR=3.53, 95% CI 2.34 to 5.33) and HIV (OR=11.00, 95% CI 3.97 to 30.51) visits. Better perceptions of resources and services were also associated with higher odds of satisfaction for both non-HIV (OR=1.66, 95% CI 1.08 to 2.55) and HIV (OR=4.68, 95% CI 1.81 to 12.10) visits. Two additional dimensions of perceived quality of care—healthcare delivery and accessibility of care—were positively associated with higher satisfaction for non-HIV patients. The odds of overall satisfaction were lower in rural facilities for non-HIV patients (OR 0.69; 95% CI 0.48 to 0.99) and HIV patients (OR=0.26, 95% CI 0.16 to 0.41). For non-HIV patients, the odds of satisfaction were greater in hospitals compared with health centres/posts (OR 1.78; 95% CI 1.27 to 2.48) and lower at publicly-managed facilities (OR=0.41, 95% CI=0.27 to 0.64).ConclusionsPerceived quality of care is an important driver of patient satisfaction with health service delivery in Zambia.
Safety and effectiveness of long-acting versus intermediate-acting insulin for patients with type 1 diabetes: protocol for a systematic review and individual patient data network meta-analysis
Authors: Veroniki Areti Angeliki , Straus Sharon E , Ashoor Huda M , Hamid Jemila S , Yu Catherine , Tricco Andrea C 
Published: December 2015

IntroductionThe choice of a basal insulin regimen to manage type 1 diabetes mellitus (T1DM) may have different risks of adverse events and effectiveness, due to the difference in the effectiveness of these agents across patient characteristics (eg, baseline glycosylated haemoglobin; A1C). Currently, there is a lack of high quality evidence to support the tailoring of insulin regimens according to an individual's needs. The aim of this study is to update our previous systematic review and perform an individual patient data network meta-analysis (IPD-NMA) to evaluate the comparative safety and effectiveness of long-acting versus intermediate-acting insulin in different subgroups of patients with T1DM.Methods and analysisWe will update our previous literature search from January 2013 onwards searching relevant electronic databases (eg, MEDLINE), as well as perform grey literature search through relevant society/association websites, and conference abstracts, and scan reference lists of the eligible studies. We will include randomised clinical trials of any duration examining long-acting versus intermediate-acting insulin preparations for adult patients with T1DM. We will focus on A1Cand severe hypoglycaemia outcomes. For each pairwise treatment comparison, we will combine all IPD from all studies in a single multilevel model, where each study is a different cluster. For a connected network of trials, we will perform an IPD-NMA to identify potential effect modifiers, and estimate the most effective and safe treatments for patients with different characteristics. If we are not successful in obtaining IPD for at least one study, we will include aggregated data (AD) abstracted from the included RCTs in our analysis, combining IPD and AD into a single model. We will report our results using the PRISMA-IPD statement.Ethics and disseminationThe results of this systematic review and IPD-NMA will be of interest to stakeholders and will help in improving existing guideline recommendations.PROSPERO registry numberCRD42015023511.
Declines in stillbirth and neonatal mortality rates in Europe between 2004 and 2010: results from the Euro-Peristat project
Authors: Zeitlin Jennifer , Mortensen Laust , Cuttini Marina , Lack Nicholas , Nijhuis Jan , Haidinger Gerald , Blondel Béatrice , Hindori-Mohangoo Ashna D 
Published: December 2015

BackgroundStillbirth and neonatal mortality rates declined in Europe between 2004 and 2010. We hypothesised that declines might be greater for countries with higher mortality in 2004 and disproportionally affect very preterm infants at highest risk.MethodsData about live births, stillbirths and neonatal deaths by gestational age (GA) were collected using a common protocol by the Euro-Peristat project in 2004 and 2010. We analysed stillbirths at ≥28 weeks GA in 22 countries and live births ≥24 weeks GA for neonatal mortality in 18 countries. Per cent changes over time were assessed by calculating risk ratios (RR) for stillbirth, neonatal mortality and preterm birth rates in 2010 vs 2004. We used meta-analysis techniques to derive pooled RR using random-effects models overall, by GA subgroups and by mortality level in 2004.ResultsBetween 2004 and 2010, stillbirths declined by 17% (95% CI 10% to 23%), with a range from 1% to 39% by country. Neonatal mortality declined by 29% (95% CI 23% to 35%) with a range from 9% to 67%. Preterm birth rates did not change: 0% (95% CI −3% to 3%). Mortality declines were of a similar magnitude at all GA; mortality levels in 2004 were not associated with RRs.ConclusionsStillbirths and neonatal deaths declined at all gestational ages in countries with both high and low levels of mortality in 2004. These results raise questions about how low-mortality countries achieve continued declines and highlight the importance of improving care across the GA spectrum.
Effect of short-term positive airway pressure on blood pressure in controlled hypertensive patients with obstructive sleep apnoea syndrome: a prospective cohort study
Authors: de Morais Lima José Heriston , da Cruz Santos Amilton , Barros Sandra Emília Benício , Soares de Abreu Morais Pollyana , Figueiroa José Natal , Alves João Guilherme B 
Published: December 2015

AbstractBackgroundObstructive sleep apnoea syndrome (OSAS) is associated with cardiovascular disease, especially in patients with high blood pressure. Continuous positive airway pressure (CPAP) seems to contribute to blood pressure control in patients with OSAS, mainly those with uncontrolled hypertension. However, the effect of CPAP on controlled hypertensive patients with OSAS is not known.ObjectiveTo evaluate the effects of CPAP on blood pressure of controlled hypertensive patients with OSAS.DesignProspective cohort study.Patients36 recently diagnosed patients with OSAS and hypertension controlled with oral antihypertensive medication.MethodsCPAP was performed for 5 days. Systolic and diastolic blood pressure were recorded at baseline and 5 days later using 24 h ambulatory blood pressure measurement.ResultsMean (SD) 24 h systolic blood pressure was reduced from 128.9 (3.4) to 126.5 (3.5), p&lt;0.001 and mean (SD) 24 h diastolic blood pressure was reduced from 86.9 (3.3) to 84.8 (3.3), p&lt;0.001. A reduction in the proportion of ‘non-dippers’ in the participants was registered (from 40.6% at baseline to 18.2%).ConclusionsA short course of CPAP may reduce systolic and diastolic blood pressure in patients with OSAS and controlled hypertension.Trial registration numberRBR – 386qsg; Brazilian Clinical Trials Registry (REBEC).
TNF-α in a molecularly targeted therapy of psoriasis and psoriatic arthritis
Authors: Wcisło-Dziadecka Dominika , Zbiciak-Nylec Martyna , Brzezińska-Wcisło Ligia , Mazurek Urszula 
Published: December 2015

AbstractPsoriasis is a chronic immunological skin disease and patients with this disorder typically experience a significant decrease in their quality of life. The disease is traditionally managed with topical and systemic agents (retinoids, ciclosporin A, methotrexate), but these treatment options are often long-term and their effects can be inconsistent and not ideal. The use of biological drugs in dermatological treatment is relatively new and began in the early 2000s. It should be noted that, in most countries, in order for biological treatment to be administered, specific criteria must be met. The current treatment options for psoriasis and psoriatic arthritis include tumour necrosis factor alpha (TNF-α) blockers, interleukin (IL)-12 and IL-23 inhibitors, T cell inhibitors and B cell inhibitors. These classes of biological drugs are characterised by protein structure as well as high molecular weight and their effectiveness is evaluated based on the Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA) and the Dermatology Life Quality Index (DLQI). TNF-α antagonists are one such class of biological drugs which includes infliximad, etanercept and adalimumab. Infliximab is a chimeric protein that is administered via intravenous infusions as a monotherapy in psoriasis vulgaris. Etanercept is indicated for use in both psoriasis vulgaris and psoriatic arthritis and it is the only drug that can be used as a treatment for children under the age of 8 with psoriasis. The drug is administered subcutaneously. Finally, adalimumab is a fully human monoclonal antibody that neutralises both free and membrane-bound TNF-α and is used in the treatment of psoriasis vulgaris and psoriatic arthritis. This article reviews the latest research in the use of TNF-α for the treatment of moderate to severe psoriasis and psoriatic arthritis. The results of research in this field are promising and confirm the effectiveness and safety of biological drugs as dermatological treatments for psoriasis. In particular, adalimumab, etanercept and infliximab are promising therapeutic options for patients with moderate to severe psoriasis and psoriatic arthritis who are unresponsive to conventional treatment strategies and they can significantly improve the quality of lives in patients with this disease.