A surveillance study to determine the accuracy of mild traumatic brain injury diagnosis in an emergency department: protocol for a retrospective cohort study

Introduction

Previous literature confirms that a mild traumatic brain injury (mTBI) may result in long-term emotional impacts and, in vulnerable subgroups, cognitive deficits. The accurate diagnosis of mTBI and its written documentation is an important first step towards providing appropriate and timely clinical care. Surveillance studies involving emergency department (ED) and hospital-based data need to be prioritised as these provide incident mTBI estimates. This project will advance existing research findings by estimating the occurrence of mTBI among those attending an ED and quantifying the accuracy of mTBI diagnoses recorded by ED staff through a comprehensive audit of ED records.

Methods and analysis

Retrospective chart reviews (between June 2015 and June 2016) of electronic clinical records from an ED in Sydney (New South Wales, Australia) will be conducted. The study population will include persons aged 18–65 years who attended the ED with any clinical features potentially indicative of mTBI. The WHO operational criteria for the clinical identification of mTBI cases is the presence of: (1) a Glasgow Coma Scale (GCS) of 13–15 after 30 min postinjury or on presentation to hospital; (2) one or more of the following: post-traumatic amnesia (PTA) of less than 24 hours' duration, confusion or disorientation, a witnessed loss of consciousness for ≤30 min and/or a positive CT brain scan. We estimate that 30 000 ED attendances will be screened and that a sample size of 500 cases with mTBI will be identified during this 1-year period, which will provide reliable estimates of mTBI occurrence in the ED setting.

Ethics and dissemination

The study was approved by the Northern Sydney Local Health District Ethics Committee. The committee deemed this study as low risk in terms of ethical issues. The written papers from this study will be submitted for publication in quality peer-reviewed medical and health journals. Study findings will be disseminated via presentations at national/international conferences and peer-reviewed journals.

http://ift.tt/2ud0ESN

Optimal dose of succinylcholine for laryngeal mask airway insertion: systematic review, meta-analysis and metaregression of randomised control trials

Objectives

To evaluate the optimal dose of succinylcholine for laryngeal mask airway (LMA) insertion and all related morbidities.

Design

Systematic review, meta-analysis and metaregression of randomised controlled trials (RCTs).

Data source and study eligibility criteria

A comprehensive search of RCTs in the PubMed, Embase, the Cochrane Library and the ClinicalTrials.gov registry up to July 2016 and articles that evaluated the use of succinylcholine chloride for LMA insertion were included in the analyses. The relative risk (RR) and the corresponding 95% CIs were determined.

Intervention

Succinylcholine as the coinduction agent and the doses were divided into mini (≤0.3 mg/kg) and low (0.3–1.0 mg/kg) doses for dose-dependent effect analyses.

Primary and secondary outcomes

The primary outcome was the first-attempt LMA insertion failure rate. Secondary outcomes included all related adverse events.

Results

Data from 10 RCTs comprising 625 participants showed that succinylcholine reduced the first-attempt LMA insertion failure rate (RR, 0.22; 95% CI 0.12 to 0.43), coughing and gagging (RR, 0.26; 95% CI 0.15 to 0.45) and laryngospasm (RR, 0.14; 95% CI 0.05 to 0.39). The use of succinylcholine did not result in a significant increase of postoperative myalgia (RR, 2.58; 95% CI 0.79 to 8.44) and did not reduce the risk of postoperative sore throat (RR, 0.76; 95% CI 0.55 to 1.03). Subgroup analysis further showed that low-dose succinylcholine reduced the LMA insertion failure rate and its related coughing and gagging when compared with mini dose.

Conclusion

The use of succinylcholine compared with none can facilitate LMA insertion and reduce insertion-related reflexes without significant postoperative myalgia. However, additional prospective studies with a larger sample size are required to fully evaluate the dose-dependent effect and complications of succinylcholine for LMA insertion.

http://ift.tt/2utiQCQ

Effect of single family rooms for preterm infants on neurodevelopment: study protocol for a systematic review

Introduction

Preterm infants are at an increased risk for neurodevelopmental delay. They have to endure many stressors in early life, including parent-infant separation, noise and painful procedures during hospitalisation in the highly technological environment of the modern neonatal ward. Currently, a shift is being noticed in the architectural design of neonatal wards towards single family rooms instead of the common open bay units. The influence of the hospital environment on health and specifically neurodevelopment in this vulnerable patient population remains under discussion.

Objectives

To assess the effect of single family rooms during hospitalisation primarily on neurodevelopment in preterm infants. Secondary outcome measures will be neonatal (ie, breastfeeding rates, sepsis, growth during hospital stay, length of hospital stay) and parental (ie, parental stress, satisfaction, participation, presence and self-efficacy).

Methods and analysis

The PRISMA-P 2015 (Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015) 17 items checklist was used for the generation of the protocol for this review. The following PICO was formulated: Population: preterm infants with need of hospitalisation in the neonatal ward; Intervention: single family rooms; Comparison: standard neonatal care in open bay units; Outcome: neurodevelopmental outcome of infants from 9 months onwards. If at least two studies, with low or moderate risk of bias, suitable for inclusion are found a meta-analysis will be performed. If quantitative synthesis is not appropriate the data will be presented descriptively.

Dissemination plans

This will be the first review, systematically assessing the effect of single family rooms on neurodevelopmental outcome in preterm infants. Clinical practice could possibly be optimised to ameliorate neurodevelopment in this vulnerable patient population based on these insights. This systematic review will be published in an international peer-reviewed journal.

Registration

We registered this systematic review protocol with the PROSPERO (International Prospective Register of Systematic Reviews) on 2 November 2016 (registration number: CRD42016050643).

Ethics

We will use data from patients enrolled in studies and/or trials already approved by the relevant ethical committees and therefore this systematic review requires no further permissions.

http://ift.tt/2v5tV0o

Integrating the perspectives of individuals with spinal cord injuries, their family caregivers and healthcare professionals from the time of rehabilitation admission to community reintegration: protocol for a scoping study on SCI needs

Introduction

There is fragmented information about the different needs following a spinal cord injury (SCI). Expressed SCI needs can be met or unmet, they change along the rehabilitation continuum (eg, acute, rehabilitation and reintegration into the community) and can be different for traumatic and non traumatic SCI. The general objective of this scoping study is to evaluate and integrate the needs of individuals with traumatic and non-traumatic SCI, their family caregivers and those reported by rehabilitation professionals from the time of rehabilitation admission to community reintegration. The specific objectives are to: (A) synthesise the needs of individuals with SCI as perceived by themselves, their family caregivers and rehabilitation professionals using two theoretical models, (B) classify needs as met and unmet, (C) explore the evolution of met/unmet needs from the time of rehabilitation admission to community reintegration and (D) provide recommendations to improve SCI care.

Methods and analysis

(A) identifying the most frequent met and unmet needs reported by adults with traumatic and non-traumatic SCI, their family caregivers and their rehabilitation professionals from the time of rehabilitation admission to community reintegration; (B) identifying relevant studies with a search in electronic databases; (C) charting the data based on categories refined and adjusted with a stakeholder group; (D) collating, summarising and reporting the results using two analytical frameworks (Maslow's hierarchical model of human needs and the Ferrans et al's model of health-related quality of life) and (E) a stakeholder consultation phase.

Ethics and dissemination

The results of this scoping study will allow understanding SCI needs from the time of rehabilitation admission to community reintegration from the perspective of different stakeholders. An integrated master report combining the needs of individuals with SCI from the perspectives of different stakeholders from the time of rehabilitation admission to community reintegration will follow the consultation meetings.

http://ift.tt/2uthati

Evaluation of DementiaNet, a network-based primary care innovation for community-dwelling patients with dementia: protocol for a longitudinal mixed methods multiple case study

Introduction

Primary healthcare professionals will increasingly be required to manage and optimise their treatment for patients with dementia. With DementiaNet, we aim to reduce the burden of dementia on healthcare services and society through implementation and facilitation of integrated network-based care with increased dementia expertise. DementiaNet is designed as a stepwise approach including clinical leadership, quality improvement cycles and interprofessional training, which are tailor-made to the local context. For example, the composition of the network and improvement goals are tailored to the local context and availability. Here, we describe the linked evaluation study which aims to provide insight in effectiveness, process and mechanism of the DementiaNet approach through an innovative evaluation design.

Methods and analysis

We designed a longitudinal, mixed methods, multiple case study. Study population consists of two levels: (i) local DementiaNet networks of primary care professionals and (ii) patients and informal caregivers who receive care from these networks. At the start and after 12 and 24 months, quantitative data are collected for each network on: level of network maturity, quality of care indicators and outcomes reported by informal caregivers of dementia patients. We assess changes in networks over time and the association with quality of care and informal caregiver-reported outcomes. Throughout the study, logs about each network are registered. Additionally, semi-structured interviews with network members and informal caregivers will provide insight in experiences and opinions regarding effects and mechanisms through which changes in quantitative outcomes are effectuated. Rich narratives will be constructed about the development of the local networks using collected data.

Ethics and dissemination

The study protocol was reviewed by the local medical ethics committee; formal judgement was not required (protocol number: 2015–2053). The findings of this study will be disseminated through peer-reviewed publications, conference presentations and presentations for healthcare professionals where appropriate.

http://ift.tt/2ud40VR

The postoperative handover: a focus group interview study with nurse anaesthetists, anaesthesiologists and PACU nurses

Objectives

To investigate different professionals' (nurse anaesthetists', anaesthesiologists', and postanaesthesia care unit nurses') descriptions of and reflections on the postoperative handover.

Design

A focus group interview study with a descriptive design using qualitative content analysis of transcripts.

Setting

One anaesthetic clinic at two hospitals in Sweden.

Participants

Six focus groups with 23 healthcare professionals involved in postoperative handovers. Each group was homogeneous regarding participant profession, resulting in two groups per profession: nurse anaesthetists (n=8), anaesthesiologists (n=7) and postanaesthesia care unit nurses (n=8).

Results

Patterns and five categories emerged: (1) having different temporal foci during handover, (2) insecurity when information is transferred from one team to another, (3) striving to ensure quality of the handover, (4) weighing the advantages and disadvantages of the bedside handover and (5) having different perspectives on the transfer of responsibility. The professionals' perceptions of the postoperative handover differed with regard to temporal foci and transfer of responsibility. All professional groups were insecure about having all information needed to ensure the quality of care. They strived to ensure quality of the handover by: focusing on matters that deviated from the normal course of events, aiding memory through structure and written information and cooperating within and between teams. They reported that the bedside handover enhances their control of the patient but also that it could threaten the patient's privacy and that frequent interruptions could be disturbing.

Conclusions

The present findings revealed variations in different professionals' views on the postoperative handover. Healthcare interventions are needed to minimise the gap between professionals' perceptions and practices and to achieve a shared understanding of postoperative handover. Furthermore, to ensure high-quality and safe care, stakeholders/decision makers need to pay attention to the environment and infrastructure in postanaesthesia care.

http://ift.tt/2utmQDp

Improving discharge care: the potential of a new organisational intervention to improve discharge after hospitalisation for acute stroke, a controlled before-after pilot study

Objective

Provision of a discharge care plan and prevention therapies is often suboptimal. Our objective was to design and pilot test an interdisciplinary, organisational intervention to improve discharge care using stroke as the case study using a mixed-methods, controlled before–after observational study design.

Setting

Acute care public hospitals in Queensland, Australia (n=15). The 15 hospitals were ranked against a benchmark based on a composite outcome of three discharge care processes. Clinicians from a 'top-ranked' hospital participated in a focus group to elicit their success factors. Two pilot hospitals then participated in the organisational intervention that was designed with experts and consumers.

Participants

Hospital clinicians involved in discharge care for stroke and patients admitted with acute stroke or transient ischaemic attack.

Intervention

A four-stage, multifaceted organisational intervention that included data reviews, education and facilitated action planning.

Primary and secondary outcome measures

Three discharge processes collected in Queensland hospitals within the Australian Stroke Clinical Registry were used to select study hospitals: (1) discharge care plan; (2) antihypertensive medication prescription and (3) antiplatelet medication prescription (ischaemic events only). Primary measure: composite outcome. Secondary measures: individual adherence changes for each discharge process; sensitivity analyses. The performance outcomes were compared 3 months before the intervention (preintervention), 3 months postintervention and at 12 months (sustainability).

Results

Data from 1289 episodes of care from the two pilot hospitals were analysed. Improvements from preintervention adherence were: antiplatelet therapy (88%vs96%, p=0.02); antihypertensive prescription (61%vs79%, p<0.001); discharge planning (72%vs94%, p<0.001); composite outcome (73%vs89%, p<0.001). There was an insignificant decay effect over the 12-month sustainability period (composite outcome: 89% postintervention vs 85% sustainability period, p=0.08).

Conclusion

Discharge care in hospitals may be effectively improved and sustained through a staged and peer-informed, organisational intervention. The intervention warrants further application and trialling on a larger scale.

http://ift.tt/2ucssa5

Associations between highly active antiretroviral therapy and the presence of HPV, premalignant and malignant cervical lesions in sub-Saharan Africa, a systematic review: current evidence and directions for future research

Objectives

In sub-Saharan Africa, substantial international funding along with evidence-based clinical practice have resulted in an unparalleled scale-up of access to antiretroviral treatment at a higher CD4 count. The role and timing of highly active antiretroviral therapy (HAART) in mediating cervical disease remains unclear. The aim of this article is to systematically review all evidence pertaining to Africa and identify research gaps regarding the epidemiological association between HAART use and the presence of premalignant/malignant cervical lesions.

Method

Five databases were searched until January 2017 to retrieve relevant literature from sub-Saharan Africa. Publications were included if they addressed prevalence, incidence or clearance of human papillomavirus (HPV) infection in women undergoing HAART as well as cytological or histological neoplastic abnormalities.

Results

22 studies were included, of which seven were prospective studies. Women receiving HAART are less likely to develop squamous intraepithelial lesions (SILs). There is evidence that duration of HAART along with the CD4 count may reduce the prevalence of high-risk HPV (HR-HPV), suggesting that without HAART, severe immunosuppression increases the risk of becoming or remaining infected with HR-HPV. Furthermore, according to existent literature, the CD4 count, rather than HAART coverage or its duration, plays a central role in the prevalence of cervical intraepithelial neoplasia (CIN) 2 and CIN 3.

Conclusion

Our findings suggest a positive impact of HAART duration, in conjunction and interaction with CD4 count, on reducing the prevalence of HR-HPV. The greatest treatment effect might be seen among women starting at the lowest CD4 count, which may have a more instrumental role in cervical oncogenesis than either HAART use or the treatment duration on the prevalence of CIN 2 and CIN 3. There is still insufficient evidence to show a clear association between HAART coverage and the incidence of invasive cervical cancer. Enhanced surveillance on the impact of HAART treatment is crucial.

http://ift.tt/2utrDVv

Early prediction of physical activity level 1 year after stroke: a longitudinal cohort study

Objective

To investigate which variables present prior and early after stroke may have an impact on the level of physical activity (PA) 1 year poststroke.

Design

Prospective longitudinal cohort and logistic regression analysis.

Setting

Stroke Unit at Sahlgrenska University Hospital, Gothenburg, Sweden.

Participants

117 individuals as part of the Stroke Arm Longitudinal Study (SALGOT) admitted to the stroke unit during a period of 18 months were consecutively recruited. The inclusion criteria were: first-time stroke, impaired upper extremity function, admitted to the stroke unit within 3 days since onset, local residency and ≥18 years old. The exclusion criteria were: upper extremity condition or severe multi-impairment prior to stroke, short life expectancy and non-Swedish speaking. 77 participants followed up at 1 year poststroke were included in the analysis.

Primary outcome

PA level 1 year after stroke was assessed using a 6-level Saltin-Grimby Scale, which was first dichotomised into mostly inactive or mostly active and second into low or moderate/high level of PA.

Results

Being mostly inactive 1 year after stroke could be predicted by age at stroke onset (OR 1.07, 95% CI 1.00 to 1.13, p=0.041), functional dependency at discharge (OR 7.01, 95% CI 1.73 to 28.43, p=0.006) and prestroke PA (OR 7.46, 95% CI 1.51 to 36.82, p=0.014). Having a low level of PA 1 year after stroke could be predicted by age at stroke onset (OR 1.13, 95% CI 1.06 to 1.21, p<0.001) and functional dependency at discharge (OR 3.62, 95% CI 1.09 to 12.04, p=0.036).

Conclusions

Previous low level of PA, older age and functional dependency all provided value in predicting low PA 1 year after stroke. These results indicate that age and simple clinical evaluations early after stroke may be useful to help clinicians identify persons at risk of being insufficiently active after stroke. Further research is needed to clarify if these findings may apply to the large population of stroke survivors.

Trial registration number

ClinicalTrials.gov (NCT01115348).

http://ift.tt/2ucWxWW

Improving risk factor management for patients with poorly controlled type 2 diabetes: a systematic review of healthcare interventions in primary care and community settings

Objectives

Poorly controlled type 2 diabetes mellitus (T2DM) is a major international health problem. Our aim was to assess the effectiveness of healthcare interventions, specifically targeting patients with poorly controlled T2DM, which seek to improve glycaemic control and cardiovascular risk in primary care settings.

Design

Systematic review.

Setting

Primary care and community settings.

Included studies

Randomised controlled trials (RCTs) targeting patients with poor glycaemic control were identified from Pubmed, Embase, Web of Science, Cochrane Library and SCOPUS. Poor glycaemic control was defined as HbA1c over 59 mmol/mol (7.5%).

Interventions

Interventions were classified as organisational, patient-oriented, professional, financial or regulatory.

Outcomes

Primary outcomes were HbA1c, blood pressure and lipid control. Two reviewers independently assessed studies for eligibility, extracted data and assessed study quality. Meta-analyses were undertaken where appropriate using random-effects models. Subgroup analysis explored the effects of intervention type, baseline HbA1c, study quality and study duration. Meta-regression analyses were undertaken to investigate identified heterogeneity.

Results

Forty-two RCTs were identified, including 11 250 patients, with most undertaken in USA. In general, studies had low risk of bias. The main intervention types were patient-directed (48%) and organisational (48%). Overall, interventions reduced HbA1c by –0.34% (95% CI –0.46% to –0.22%), but meta-analyses had high statistical heterogeneity. Subgroup analyses suggested that organisational interventions and interventions on those with baseline HbA1c over 9.5% had better improvements in HbA1c. Meta-regression analyses suggested that only interventions on those with population HbA1c over 9.5% were more effective. Interventions had a modest improvement of blood pressure and lipids, although baseline levels of control were generally good.

Conclusions

This review suggests that interventions for T2DM, in primary care, are better targeted at individuals with very poor glycaemic control and that organisational interventions may be more effective.

http://ift.tt/2utiHPO

Active Play in After-school Programmes: development of an intervention and description of a matched-pair cluster-randomised trial assessing physical activity play in after-school programmes

Introduction

Interventions delivered in after-school programmes (ASPs) have the potential to become a means of ensuring adequate physical activity among schoolchildren. This requires a motivational climate, allowing for self-determined play. If trained, ASP staff may represent a valuable resource for supporting such play. Increasing knowledge and supportive skills among ASP staff may also potentially increase their motivation for work. The purpose of this article is to describe the development of the 'Active Play in ASP' intervention, which aims to promote physical activity among first graders attending ASP, and to present a protocol for a matched-pair cluster-randomised trial to evaluate the intervention.

Methods and analysis

Informed by experiences from practice, evidence-based knowledge and theory, the intervention was developed in a stepwise process including focus group meetings and a small-scale pilot test. The intervention contains a course programme for ASP staff to increase their skills in how to support physical activity through play. In a cluster randomised controlled trial, the ASPs will be matched and randomly allocated to receive the 7-month intervention or to a control group. Outcomes will be assessed at baseline, after 7 and 19 months. First graders attending the ASPs included are eligible. The primary outcome will be accelerometer-determined minutes in moderate to vigorous physical activity in the ASP. The study uses a mixed methods approach including observations and interviews to provide rich descriptions of the concept of children's physical activity in ASP. Moreover, the trial will assess whether the ASP staff benefits from participation in the intervention in terms of increased work motivation. Lastly, process evaluations of programme fidelity, satisfaction and suggestions on improvement will be performed.

Ethics and dissemination

The study is approved by the Data Protection Official for Research (reference no 46008). Results will be presented in conferences and peer-reviewed journals.

Trial registration number

Clinical Trials (NCT02954614), pre-results.

http://ift.tt/2v5UVgs

Electroacupuncture to alleviate postoperative pain after a laparoscopic appendectomy: study protocol for a three-arm, randomised, controlled trial

Background

The purpose of this study is to evaluate the efficacy and safety of electroacupuncture (EA) for postoperative pain after laparoscopic appendectomy compared with sham electroacupuncture (SEA) and no acupuncture treatment.

Methods and analysis

This study is a protocol for a three-arm, randomised, patient-assessor-blinded (to the type of acupuncture treatment), controlled, parallel trial. 138 participants diagnosed with appendicitis and scheduled for laparoscopic appendectomy will be randomly assigned to the EA group (n=46), SEA group (n=46) or control group (n=46). The EA group will receive acupuncture treatment at both regional and distal acupuncture points with electrostimulation. The SEA group will receive sham acupuncture treatment with mock electrostimulation. Both EA and SEA groups will receive a total of four treatments 1 hour preoperative, 1 hour postoperative and during the morning and afternoon the day after surgery with the same routine postoperative pain control. The control group will receive only routine postoperative pain control. The primary outcome is the 11-point Pain Intensity Numerical Rating Scale (PI-NRS) at 24 hours after surgery. The secondary outcomes are the PI-NRS, analgesic consumption, opioid-related side effects, time to first passing flatus, quality of life and adverse events evaluated 6, 12, 24 and 36 hours and 7 days after surgery.

Ethics and dissemination

The study was planned in accordance with the Helsinki Declaration and the Korean Good Clinical Practice Guidelines to protect the participants and was approved by the institutional review board (IRB) of Kyung Hee University Medical Center (KMC IRB-1427–02). The results will be disseminated in peer-reviewed journals and presented at international conferences.

Trial registration number

Clinical Research Information Service (KCT0001328).

http://ift.tt/2utmQ6n

Challenges and facilitators for health professionals providing primary healthcare for refugees and asylum seekers in high-income countries: a systematic review and thematic synthesis of qualitative research

Objectives

To thematically synthesise primary qualitative studies that explore challenges and facilitators for health professionals providing primary healthcare for refugees and asylum seekers in high-income countries.

Design

Systematic review and qualitative thematic synthesis.

Methods

Searches of MEDLINE, EMBASE, PsycINFO, CINAHL and Web of Science. Search terms were combined for qualitative research, primary healthcare professionals, refugees and asylum seekers, and were supplemented by searches of reference lists and citations. Study selection was conducted by two researchers using prespecified selection criteria. Data extraction and quality assessment using the Critical Appraisal Skills Programme tool was conducted by the first author. A thematic synthesis was undertaken to develop descriptive themes and analytical constructs.

Results

Twenty-six articles reporting on 21 studies and involving 357 participants were included. Eleven descriptive themes were interpreted, embedded within three analytical constructs: healthcare encounter (trusting relationship, communication, cultural understanding, health and social conditions, time); healthcare system (training and guidance, professional support, connecting with other services, organisation, resources and capacity); asylum and resettlement. Challenges and facilitators were described within these themes.

Conclusions

A range of challenges and facilitators have been identified for health professionals providing primary healthcare for refugees and asylum seekers that are experienced in the dimensions of the healthcare encounter, the healthcare system and wider asylum and resettlement situation. Comprehensive understanding of these challenges and facilitators is important to shape policy, improve the quality of services and provide more equitable health services for this vulnerable group.

http://ift.tt/2wgoeLM

Using mixed methods to assess fidelity of delivery and its influencing factors in a complex self-management intervention for people with osteoarthritis and low back pain

Objectives and design

Despite an increasing awareness of the importance of fidelity of delivery within complex behaviour change interventions, it is often poorly assessed. This mixed methods study aimed to establish the fidelity of delivery of a complex self-management intervention and explore the reasons for these findings using a convergent/triangulation design.

Setting

Feasibility trial of the Self-management of Osteoarthritis and Low back pain through Activity and Skills (SOLAS) intervention (ISRCTN49875385), delivered in primary care physiotherapy.

Methods and outcomes

60 SOLAS sessions were delivered across seven sites by nine physiotherapists. Fidelity of delivery of prespecified intervention components was evaluated using (1) audio-recordings (n=60), direct observations (n=24) and self-report checklists (n=60) and (2) individual interviews with physiotherapists (n=9). Quantitatively, fidelity scores were calculated using percentage means and SD of components delivered. Associations between fidelity scores and physiotherapist variables were analysed using Spearman's correlations. Interviews were analysed using thematic analysis to explore potential reasons for fidelity scores. Integration of quantitative and qualitative data occurred at an interpretation level using triangulation.

Results

Quantitatively, fidelity scores were high for all assessment methods; with self-report (92.7%) consistently higher than direct observations (82.7%) or audio-recordings (81.7%). There was significant variation between physiotherapists' individual scores (69.8% - 100%). Both qualitative and quantitative data (from physiotherapist variables) found that physiotherapists' knowledge (Spearman's association at p=0.003) and previous experience (p=0.008) were factors that influenced their fidelity. The qualitative data also postulated participant-level (eg, individual needs) and programme-level factors (eg, resources) as additional elements that influenced fidelity.

Conclusion

The intervention was delivered with high fidelity. This study contributes to the limited evidence regarding fidelity assessment methods within complex behaviour change interventions. The findings suggest a combination of quantitative methods is suitable for the assessment of fidelity of delivery. A mixed methods approach provided a more insightful understanding of fidelity and its influencing factors.

Trial registration number

ISRCTN49875385; Pre-results.

http://ift.tt/2utpWHL

The Indigenous Counselling and Nicotine (ICAN) QUIT in Pregnancy Pilot Study protocol: a feasibility step-wedge cluster randomised trial to improve health providers' management of smoking during pregnancy

Introduction

Indigenous women have the highest smoking prevalence during pregnancy (47%) in Australia. Health professionals report lack of knowledge, skills and confidence to effectively manage smoking among pregnant women in general. We developed a behaviour change intervention aimed to improve health professionals' management of smoking in Indigenous pregnant women—the Indigenous Counselling And Nicotine (ICAN) QUIT in Pregnancy. This intervention includes webinar training for health professionals, an educational resources package for health professionals and pregnant women, free oral nicotine replacement therapy (NRT) for pregnant women, and audit and feedback on health professionals' performance.

The aim of this study is to test the feasibility and acceptability of the ICAN QUIT in Pregnancy intervention to improve health professionals' provision of evidence-based culturally responsive smoking cessation care to Australian Indigenous pregnant smokers.

Methods and analysis

This protocol describes the design of a step-wedge cluster randomised pilot study. Six Aboriginal Medical Services (AMSs) are randomised into three clusters. Clusters receive the intervention staggered by 1 month. Health professionals report on their knowledge and skills pretraining and post-training and at the end of the study. Pregnant women are recruited and followed up for 3 months. The primary outcome is the recruitment rate of pregnant women. Secondary outcomes include feasibility of recruitment and follow-up of participating women, and webinar training of health professionals, measured using a designated log; and measures of effectiveness outcomes, including quit rates and NRT prescription rates.

Ethics and dissemination

In accordance with the Aboriginal Health and Medical Research Council guidelines, this study has been developed in collaboration with a Stakeholder and Consumer Aboriginal Advisory Panel (SCAAP). The SCAAP provides cultural consultation, advice and direction to ensure that implementation is acceptable and respectful to the Aboriginal communities involved. Results will be disseminated to AMSs, Aboriginal communities and national Aboriginal bodies.

Registration details

This protocol (version 4, 14 October 2016) is registered with the Australian and New Zealand Clinical Trials Registry (Ref #: ACTRN12616001603404).

http://ift.tt/2utzkL7

Conceptualising paediatric health disparities: a metanarrative systematic review and unified conceptual framework

Objective

There exists a paucity of work in the development and testing of theoretical models specific to childhood health disparities even though they have been linked to the prevalence of adult health disparities including high rates of chronic disease. We conducted a systematic review and thematic analysis of existing models of health disparities specific to children to inform development of a unified conceptual framework.

Methods

We systematically reviewed articles reporting theoretical or explanatory models of disparities on a range of outcomes related to child health. We searched Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus (database inception to 9 July 2015). A metanarrative approach guided the analysis process.

Results

A total of 48 studies presenting 48 models were included. This systematic review found multiple models but no consensus on one approach. However, we did discover a fair amount of overlap, such that the 48 models reviewed converged into the unified conceptual framework. The majority of models included factors in three domains: individual characteristics and behaviours (88%), healthcare providers and systems (63%), and environment/community (56%), . Only 38% of models included factors in the health and public policies domain.

Conclusions

A disease-agnostic unified conceptual framework may inform integration of existing knowledge of child health disparities and guide future research. This multilevel framework can focus attention among clinical, basic and social science research on the relationships between policy, social factors, health systems and the physical environment that impact children's health outcomes.

http://ift.tt/2ut02Ui

A national surveillance project on chronic kidney disease management in Canadian primary care: a study protocol

Introduction

Effective chronic disease care is dependent on well-organised quality improvement (QI) strategies that monitor processes of care and outcomes for optimal care delivery. Although healthcare is provincially/territorially structured in Canada, there are national networks such as the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) as important facilitators for national QI-based studies to improve chronic disease care. The goal of our study is to improve the understanding of how patients with chronic kidney disease (CKD) are managed in primary care and the variation across practices and provinces and territories to drive improvements in care delivery.

Methods and analysis

The CPCSSN database contains anonymised health information from the electronic medical records for patients of participating primary care practices (PCPs) across Canada (n=1200). The dataset includes information on patient sociodemographics, medications, laboratory results and comorbidities. Leveraging validated algorithms, case definitions and guidelines will help define CKD and the related processes of care, and these enable us to: (1) determine prevalent CKD burden; (2) ascertain the current practice pattern on risk identification and management of CKD and (3) study variation in care indicators (eg, achievement of blood pressure and proteinuria targets) and referral pattern for specialist kidney care. The process of care outcomes will be stratified across patients' demographics as well as provider and regional (provincial/territorial) characteristics. The prevalence of CKD stages 3–5 will be presented as age–sex standardised prevalence estimates stratified by province and as weighted averages for population rates with 95% CIs using census data. For each PCP, age–sex standardised prevalence will be calculated and compared with expected standardised prevalence estimates. The process-based outcomes will be defined using established methods.

Ethics and dissemination

The CPCSSN is committed to high ethical standards when dealing with individual data collected, and this work is reviewed and approved by the Network Scientific Committee. The results will be published in peer-reviewed journals and presented at relevant national and international scientific meetings.

http://ift.tt/2ucOOrW

Identifying and prioritising systematic review topics with public health stakeholders: A protocol for a modified Delphi study in Switzerland to inform future research agendas

Introduction

The Cochrane Collaboration aims to produce relevant and top priority evidence that responds to existing evidence gaps. Hence, research priority setting (RPS) is important to identify which potential research gaps are deemed most important. Moreover, RPS supports future health research to conform both health and health evidence needs. However, studies that are prioritising systematic review topics in public health are surprisingly rare. Therefore, to inform the research agenda of Cochrane Public Health Europe (CPHE), we introduce the protocol of a priority setting study on systematic review topics in several European countries, which is conceptualised as pilot.

Methods and analysis

We will conduct a two-round modified Delphi study in Switzerland, incorporating an anonymous web-based questionnaire, to assess which topics should be prioritised for systematic reviews in public health. In the first Delphi round public health stakeholders will suggest relevant assessment criteria and potential priority topics. In the second Delphi round the participants indicate their (dis)agreement to the aggregated results of the first round and rate the potential review topics with the predetermined criteria on a four-point Likert scale. As we invite a wide variety of stakeholders we will compare the results between the different stakeholder groups.

Ethics and dissemination

We have received ethical approval from the ethical board of the University of Bremen, Germany (principal investigation is conducted at the University of Bremen) and a certificate of non-objection from the Canton of Zurich, Switzerland (fieldwork will be conducted in Switzerland). The results of this study will be further disseminated through peer reviewed publication and will support systematic review author groups (i.a. CPHE) to improve the relevance of the groups future review work. Finally, the proposed priority setting study can be used as a framework by other systematic review groups when conducting a priority setting study in a different context.

http://ift.tt/2uty0Ik

Observational study of vascular dementia in the Spanish elderly population according to type 2 diabetes status: trends in incidence, characteristics and outcomes (2004-2013)

Objectives

To examine trends overtime in the incidence and in-hospital outcomes of vascular dementia (VaD) hospitalisations in patients aged 70 years or over suffering and not suffering from type 2 diabetes mellitus (T2DM) between 2004 and 2013 in Spain.

Design

Retrospective study.

Setting

Spain.

Participants

National hospital discharge data were used; patients aged ≥70, discharged from a hospital with VaD as a primary diagnosis, were selected.

Main outcome measures

Overall incidence, therapeutic and diagnostic procedures, comorbidities, infectious complications, duration of hospital stays and in-hospital mortality (IHM).

Results

In total, 170 607 admissions for VaD (34.3% with T2DM) were identified. We found a significant upward linear trend in the incidence of VaD for men and women with and without diabetes between 2004 and 2013. The adjusted incidence was higher among people with T2DM over the study period. We found a higher incidence in men than women in all years under study. A positive association between T2DM and VaD hospitalisation was found among both men (IRR 2.14, 95% CI 2.11 to 2.16) and women (incidence rate ratio (IRR) 2.22; 95% CI 2.19 to 2.25). Pneumonia was significantly associated with a higher mortality (OR 2.59, 95% CI 2.52 to 2.67). We found that percutaneous endoscopic gastrostomy was associated with lower IHM (OR 0.37, 95% CI 0.31 to 0.45), while parenteral nutrition had the opposite effect (OR 1.29, 95% CI 1.18 to 1.41). There was no association between diabetes and higher IHM (OR 0.99, 95% CI 0.93 to 1.06). The time-trend analyses of the entire sample showed a significant reduction in mortality in patients with VaD (OR 0.98, 95% CI 0.97 to 0.99).

Conclusions

Incidence rates for VaD hospitalisations were twice as high in patients with diabetes compared with those without. Men had significantly higher incidence rates than women, regardless of diabetes status. In both groups studied, pneumonia and parenteral nutrition were associated with mortality while percutaneous endoscopic gastrostomy was associated with survival. Having diabetes was not associated with higher IHM after hospitalisation with VaD.

http://ift.tt/2ucEwYP

Paediatric asthma control under a community management model in China: a protocol for a prospective multicentre cohort study

Introduction

Childhood asthma is globally one of the most common respiratory disorders and accounts for more school absences and more hospitalizations than any other chronic illness. The worldwide economic burden of this disease exceeds those of HIV/AIDS and tuberculosis combined. Proper intervention and effective management is of paramount importance for the control and prognosis of paediatric asthma. Unfortunately, the rate of uncontrolled and partially controlled paediatric asthma in China is >90%. This study will use a new management model to investigate the status of asthma control and the adherence of patients to a medication protocol.

Methods

This prospective, multicentre, observational study will be conducted at 15 hospitals on children (n=800) diagnosed with asthma. Each patient will be assigned to either the nearest community hospital or Shanghai Children's Medical Center, whichever is closer to the patient's home, according to the decision of parents. Participants were divided into two groups: tertiary care hospital (Shanghai Children's Medical Center) follow-up group and community hospital follow-up group. The primary outcome will be the difference in the proportion of controlled, partially controlled and uncontrolled asthma among the two groups. Secondary outcomes will be the differences in adherence rate, lung function, exacerbations, growth development, total asthma-related unscheduled visits, days absent from school and loss of working days for the patient's caregiver. Data will be analysed on an intention-to-treat and a per-protocol basis.

Ethics and dissemination

Ethics approval was obtained from the Institutional Review Board of Shanghai Children's Medical Center affiliated with Shanghai Jiao Tong University of Medicine. We plan to publish the results of this study in a peer-reviewed journal article.

http://ift.tt/2wgh5ev

Variations in hospital costs after traffic injuries: the importance of sociodemographic aspects and comorbidities

Publication date: Available online 5 August 2017
Source:Injury
Author(s): Stefanie Devos, Griet Van Belleghem, Karen Pien, Ives Hubloue, Isidoor Lauwaert, Tom Vanlier, Lieven Annemans, Koen Putman
ObjectiveThe impact of sociodemographic aspects and comorbidities on the inpatient hospital care costs of traffic victims are not clear. The main goal of this study is to provide insights into the sociodemographic characteristics and clinical conditions (including comorbidities) of the victims that result in higher hospital costs.ParticipantsFor the period 2009 − 2011, people admitted to a hospital as a result of a road traffic crash (N=64,304) were identified in the national Minimal Hospital Dataset, after which they were linked to their respective claims data from the sickness funds.MethodsA generalized linear model was used to analyse hospital costs controlling for roadway user categories, demographics (gender, age, individual socioeconomic status (SES)), and clinical factors (the nature, location, and severity of injury, and comorbidities).ResultsThe median hospital cost was € 2,801 (IQR € 1,510–€ 7,175, 2015 Euros). There was no significant difference between gender. Low SES inpatients incurred 16% (95% CI: 14% − 18%) higher hospital costs than inpatients of high SES. The presence of comorbidities was associated with an increased hospital cost, however with varying magnitude. For example traffic victims suffering from dementia incur significantly higher hospital costs than those who were not (49% higher, 95% CI: 44% − 53%), whereas diabetes was associated with a smaller increase in costs compared to non-diabetics (13%, 95% CI: 10% −16%).ConclusionComorbidities and low SES are associated with higher hospital costs for traffic victims, notwithstanding their age, and the nature and the severity of their injury. The broad variability of hospital costs among trauma inpatients should be accounted for when reconsidering financing models. Furthermore, the strong predictive value of some comorbidities and SES on hospital costs should be considered when projections of future health care utilisation in traffic safety scenarios are prepared.



http://ift.tt/2hvDqBw

Membrane complement regulatory protein reduces the damage of transplanting autologous bone marrow mesenchymal stem cells by suppressing the activation of complement

Publication date: Available online 5 August 2017
Source:Injury
Author(s): Kai Xiao, Zhenhua Fang, Xinfeng Gao, Jingjing Zhao, Ruokun Huang, Ming Xie
There are few studies on the interaction of transplanting autologous bone marrow mesenchymal stem cells (BMSCs) and complement. In order to further explore the effect of complement on BMSCs, BMSCs were obtained from bone marrow of 20 cases clinical patients, and then experimented in vitro. The cytotoxicity of complement on the mesenchymal stem cells in autologous human serum (AHS) was measured by Europium cytotoxicity assay. The complement membrane attack complex (MAC) deposited on the membrane surface was detected by flow cytometry. Finally, the cytotoxicity on BMSCs was measured after mCRPs overexpression or knockdown. We found that More than 90% of cells derived from bone marrow were identified to be mesenchymal stem cells through detection of cell membrane surface markers by flow cytometry. BMSCs harvested from the 20 patients all had cytotoxicity after incubated with AHS, and the cytotoxicity was significant higher than that incubated with complement inactivated autologous human serum (iAHS). Complement attack complex (MAC) could be detected on the BMSCs incubated with AHS, which implied the complement activation. We also found that mCRPs CD55 and CD59 overexpressions can resist the cytotoxicity induced by complement activation, while mCRPs CD55 and CD59 knockdown can enhance the cytotoxicity. Thus, the results indicated that mCRPs could effectively protect BMSCs from attacks by complement by suppressing the activation of complement.



http://ift.tt/2fgMb1q

Effects of seeding adipose-derived stem cells on electrospun nanocomposite used as chest wall graft in a murine model

Publication date: Available online 4 August 2017
Source:Injury
Author(s): Johanna Buschmann, Eleni Balli, Samuel C. Hess, Wendelin J. Stark, Paolo Cinelli, Sonja Märsmann, Manfred Welti, Walter Weder, Wolfgang Jungraithmayr
ObjectivesMalignant neoplasms infiltrating the chest wall often requires resection of the thoracic wall. To replace the defect, Gore-Tex^® is usually employed as the gold standard material, however, Gore-Tex^® is inert and not degradable. Novel materials are nowadays available which allow a full bio-integration due to their non-toxic degradability. Additionally, stem cell seeding has the capacity to reduce inflammatory response towards such grafts, thus integrating it better into the host organism.



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The incidence and trauma mechanisms of acetabular fractures: a nationwide study in Finland between 1997 and 2014

Publication date: Available online 4 August 2017
Source:Injury
Author(s): Pasi P. Rinne, Minna K. Laitinen, Tuomas Huttunen, Pekka Kannus, Ville M. Mattila
PurposeInformation on the incidence of acetabular fractures of the pelvis is limited. Epidemiological data is often based on specific trauma registers, individual trauma centres or on trends of all pelvic fractures grouped together. The primary aim of this study was to determine the incidence and trends of hospital-treated acetabular fractures in the Finnish population from 1997 to 2014. The secondary aim was to assess the trauma mechanisms involved.MethodsThe Finnish National Hospital Discharge Register collects inpatient data from all public and private medical institutions in Finland and covers the entire Finnish population of 5.5 million. For this study, we selected all persons 18 years of age or older who were admitted to hospital for the treatment of an acetabular fracture between 1997 and 2014. The main outcome variable was the annual number of patients hospitalised with a main or secondary diagnosis of acetabular fracture of the pelvis.ResultsThe overall crude incidence of acetabular fractures increased slightly (from 6.4/100 000 persons/year to 8.1/100 000 persons/year) from 1997 to 2014 while the age-standardised incidence rate remained at a similar level (7.1/100 000/persons/year in 1997 and 7.2/100 000/persons/year in 2014). An incidence increase was observed in the elderly population, whereas the incidence of acetabular fractures in the younger population (mostly high energy traumas) remained stable. The most frequent trauma mechanism for acetabular fractures was fall on the same level (47%).ConclusionsThe incidence of acetabular fractures increased slightly in Finland between 1997 and 2014. This increase was observed especially in the elderly population and the ageing of the population largely explains the rise. The incidence of acetabular fractures in the younger population decreased. The most common trauma mechanism was falling on the same level.



http://ift.tt/2fgwtTX

Long-term follow-up evaluation of autologous chondrocyte implantation for symptomatic cartilage lesions of the knee: a single-centre prospective study

Publication date: Available online 4 August 2017
Source:Injury
Author(s): M. Berruto, P. Ferrua, S. Pasqualotto, F. Uboldi, A. Maione, P. Zedde, E. Usellini
IntroductionAutologous Chondrocyte Implantation (ACI) has been the first technique in reconstruction of a valid articular surface. The aim of this study was to evaluate clinical results of this technique at an average follow up of 162±27months (range 88-208) in a group of patients who underwent ACI.Materials and Methods32 patients were operated between 1997 and 2007 for chondral lesions or osteochondritis dissecans of the knee. Mean size of the defect was 5.48cm2±1.53 (range 2-9). Nine patients were treated with I generation technique and 23 with II generation. All patients were evaluated with Subjective IKDC and Tegner Activity Scales for clinical outcomes and with EQ-VAS for a quantitative measure of health after intervention, starting from pre-operative period and at regular follow up (minimum 88 months-maximum 208 months).ResultsA significant increment of all scores was noticed comparing preoperative and postoperative results. In particular medium IKDC score increased from 40.3±9.6 in preoperative evaluation to 74.2±11.6 at one year (p<0.00001) and to 83.9±10.4 at 5 years follow up (p<0.001). Mean IKDC values at the last follow-up were 80.3±14.2, showing no statistical differences with those obtained at five-year follow-up. Tegner Activity Scale values increased from 2.8±1.1 preoperatively to 4.1±1.1 (p<0.0001) after one year and to 6±1.1 at five years (p<0.0001). Mean Tegner Activity Scale values decreased to 4.8±1.4 at the last follow-up. EQ-VAS evaluation showed superposable results comparing the 5 years evaluation with the ones at a medium follow up of 162±27months.DiscussionThe most important finding is the reliability at long-term of ACI technique, which in our series gave excellent clinical results. No statistical differences were observed between first- and second-generation. Clinical outcomes were significantly better for defects in the femoral condyles, influenced by age (worse results over 30 years old).ConclusionsACI represents a valid technique for chondral and osteochondral lesions of the knee in a population heterogeneous for age, sex and activity level with good results even at a long term follow up.



http://ift.tt/2hvDbGC

A prospective analysis of injury rates, patterns and causes in Cliff and Splash Diving

Publication date: Available online 5 August 2017
Source:Injury
Author(s): Lukas Ernstbrunner, Armin Runer, Paul Siegert, Matthäus Ernstbrunner, Johannes Becker, Thomas Freude, Herbert Resch, Philipp Moroder
IntroductionInformation about injuries and its differences in Cliff Diving (CD) and Splash Diving (SD) are unknown. It was the aim to analyse (1) injury rates, patterns and causes; (2) difference (in injuries) between both disciplines; and to (3) identify targets for future injury prevention interventions.MethodsFrom April to November 2013, 81 cliff and 51 splash divers were prospectively surveyed with an encrypted, monthly e-mail-based questionnaire.ResultsDuring a total of 7,857h diving with an average diving height of 15m (±8), an overall injury rate of 7.9 injuries/1,000hours of sport exposure was reported. Cliff divers most commonly suffered from injuries of the foot and ankle (18%; n=24) and neck and cervical spine (14%; n=19). In SD, the lower limb was in 52% (n=43) and lower back (23%; n=19) were most frequently involved. In 79% (n=49) of the cases, the injury happened while entering the water. Cliff divers were in 52% (n=15) of the injuries in a feet-first or head-first position (14%; n=4) and splash divers were in 45% (n=9) of the injuries in a back- or buttocks-first position. Most of the injuries were bruises (47%; n=104) and muscle strains (13%; n=28). The injury risk during practice was significantly higher than in competition (11.3 vs. 4.5 injuries/1,000h; OR 2.5; p=0.001). The injury risk of experts (15.4/1,000h exposure) was significantly higher than in professionals (6.3/1,000h exposure; OR 2.4; 95% CI, 3.3-1.9; p<0.001), although the average diving height was higher in professionals (19m ±8 vs. 12m±6; p<0.001). Significantly more professionals performed dryland training compared to experts (p=0.006).ConclusionMost of the injuries are related to the water entry. The entry position plays a key role in injury patterns with pursuant differences comparing CD with SD. Although most of the injuries involved soft-tissue only, severe injuries have been reported. Targets for future injury prevention strategies include protection for the increased impaction at entry; adaption of the diving conditions in practice to those in competition; dryland training courses; and instruction of non-professional divers to teach appropriate diving techniques.



http://ift.tt/2fgXBlU

Non neurologic burst thoracolumbar fractures fixation: case-control study

Publication date: Available online 4 August 2017
Source:Injury
Author(s): Aymeric Amelot, Joseph Cristini, Alexis Moles, Celine Salaud, Olivier Hamel, Eric Bord, Kevin Buffenoir
Study designBurst fractures not associated with any neurological deficits are frequent but not therapeutic agreement on their management is available to date. This case-control study was conducted to try to help guide therapeutic decision in the treatment of such fractures.Materials and methodsThis case-control study includes consecutive retrospective evaluation of 25 case-patients treated by posterior short-segment fixation associated with kyphoplasty (SFK) in the treatment of A3 thoracolumbar unstable fractures, as compared to a control-group composed of 82 patients treated by long-segment (LF) pedicle screws.ResultsSFK patients bled significantly less than the LF patients (p=0.04). Assessment of deformation progression, vertebral height restoration and reduction of the regional kyphotic angle in the SFK and LF groups revealed no statistically significant superiority of one approach on another. In contrast, the height of endplates was significantly increased in the SFK group (p=0.006). The patients' pain levels were significantly improved in the SFK group (p=0.002). However, patients from the SFK group stood earlier postoperatively (1.7 vs 3.7 days, p=0.001).ConclusionWe believe that SFK in vertebral fractures is as efficient as LF for bone consolidation and spine stabilization. In addition, SFK patients may use fewer analgesics.



http://ift.tt/2hwkaDV

Paediatric fracture clinic re-design: incorporating a virtual fracture clinic

Publication date: Available online 4 August 2017
Source:Injury
Author(s): Paul M. Robinson, Francis Sim, Mark Latimer, Piers D. Mitchell
IntroductionThe use of virtual fracture clinics (VFCs) and home management protocols is increasing. The main aim of this research is to determine whether a paediatric home management programme and VFC can be used safely to manage a range of suitable fractures in children.Materials and MethodsProtocols for the home management of stable paediatric fractures were designed by two consultant paediatric orthopaedic surgeons. These were for children between the ages of 18 months and 15 years 364 days. A new tariff was negotiated with the clinical commissioning groups (CCGs) for a VFC new patient review. A prospective analysis was performed for the first 2 months of the programme. Further review periods were undertaken 6 months later and 12 months after that.ResultsSixty-five patients were reviewed in the first 10 VFCs (mean 6.5 cases per week). After 6 months, 164 patients were reviewed in a 3-month period in the VFC, a mean of 11 cases per week. A year later the number of patients reviewed in the VFC had continued to increase with a total of 253 patients in 3 months, mean 21 cases per week. This gave a saving to the CCG of £45,000 per year and to the hospital of £106,000 per year. There were no serious adverse consequences to any patients from the use of the pathway.Discussion and ConclusionWe have reported on the introduction of a paediatric VFC and a home management programme for stable paediatric fractures. We are not aware of any reports in the orthopaedic literature that have described such a comprehensive and innovative re-organisation of paediatric fracture services. We estimate that the NHS could save approximately £10.1 million if all hospitals in England introduced this.



http://ift.tt/2fgM3is

Blocking protein quality control to counter hereditary cancers

Abstract

Inhibitors of molecular chaperones and the ubiquitin-proteasome system have already been clinically implemented to counter certain cancers, including multiple myeloma and mantle cell lymphoma. The efficacy of this treatment relies on genomic alterations in cancer cells causing a proteostatic imbalance, which makes them more dependent on protein quality control (PQC) mechanisms than normal cells. Accordingly, blocking PQC, e.g. by proteasome inhibitors, may cause a lethal proteotoxic crisis in cancer cells, while leaving normal cells unaffected. Evidence, however, suggests that the PQC system operates by following a better-safe-than-sorry principle and is thus prone to target proteins that are only slightly structurally perturbed, but still functional. Accordingly, implementing PQC inhibitors may also, through an entirely different mechanism, hold potential for other cancers. Several inherited cancer susceptibility syndromes, such as Lynch syndrome and von Hippel-Lindau disease, are caused by missense mutations in tumor suppressor genes, and in some cases the resulting amino acid substitutions in the encoded proteins cause the cellular PQC system to target them for degradation, although they may still retain function. As a consequence of this over-meticulous PQC mechanism, the cell may end up with an insufficient amount of the abnormal, but functional, protein, which in turn leads to a loss-of-function phenotype and manifestation of the disease. Increasing the amounts of such proteins by stabilizing with chemical chaperones, or by targeting molecular chaperones or the ubiquitin-proteasome system, may thus avert or delay the disease onset. Here we review the potential of targeting the PQC system in hereditary cancer susceptibility syndromes. This article is protected by copyright. All rights reserved.

http://ift.tt/2fgKYaw

Validation of the Australian Midwifery Standards Assessment Tool (AMSAT): A tool to assess midwifery competence

Publication date: Available online 4 August 2017
Source:Women and Birth
Author(s): Linda Sweet, Maryam Bazargan, Lois McKellar, Joanne Gray, Amanda Henderson
BackgroundThere is no current validated clinical assessment tool to measure the attainment of midwifery student competence in the midwifery practice setting. The lack of a valid assessment tool has led to a proliferation of tools and inconsistency in assessment of, and feedback on student learning.ObjectiveThis research aimed to develop and validate a tool to assess competence of midwifery students in practice-based settings.DesignA mixed-methods approach was used and the study implemented in two phases. Phase one involved the development of the AMSAT tool with qualitative feedback from midwifery academics, midwife assessors of students, and midwifery students. In phase two the newly developed AMSAT tool was piloted across a range of midwifery practice settings and ANOVA was used to compare scores across year levels, with feedback being obtained from assessors.FindingsAnalysis of 150 AMSAT forms indicate the AMSAT as: reliable (Cronbach alpha greater than 0.9); valid—data extraction loaded predominantly onto one factor; and sensitivity scores indicating level of proficiency increased across the three years. Feedback evaluation forms (n=83) suggest acceptance of this tool for the purpose of both assessing and providing feedback on midwifery student's practice performance and competence.ConclusionThe AMSAT is a valid, reliable and acceptable midwifery assessment tool enables consistent assessment of midwifery student competence. This assists benchmarking across midwifery education programs.



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Viral cancer therapies: are they ready for combination with other immunotherapies?

Future Oncology, Ahead of Print.


http://ift.tt/2vz30uF

Cancer stem cell research in Iran: potentials and challenges

Future Oncology, Ahead of Print.


http://ift.tt/2u9XniZ

Local therapy for triple-negative breast cancer: a comprehensive review

Future Oncology, Ahead of Print.


http://ift.tt/2vyLB5m

Serum metabolomics can predict the outcome of first systematic transrectal prostate biopsy in patients with PSA

Future Oncology, Ahead of Print.


http://ift.tt/2uals9j

Treatment of adult acute lymphoblastic leukemia with inotuzumab ozogamicin

Future Oncology, Ahead of Print.


http://ift.tt/2vz82Hy

Are peptide vaccines viable in combination with other cancer immunotherapies?

Future Oncology, Ahead of Print.


http://ift.tt/2uai26I

Immunomodulatory effects of current cancer treatment and the consequences for follow-up immunotherapeutics

Future Oncology, Ahead of Print.


http://ift.tt/2vzaihV

The importance for immunoregulation for long-term cancer control

Future Oncology, Ahead of Print.


http://ift.tt/2u9Z5AW

“Is immunotherapy a viable option in treating mesothelioma?”

Future Oncology, Ahead of Print.


http://ift.tt/2vyUxYw

Cancer pain management: recommendations from a Latin-American experts panel

Future Oncology, Ahead of Print.


http://ift.tt/2u9Z4gs

Pharmacogenetics and the treatment of asthma

Pharmacogenomics, Ahead of Print.


http://ift.tt/2vBmMqr

Falls: the adverse drug reaction of the elderly and the impact of pharmacogenetics

Pharmacogenomics, Ahead of Print.


http://ift.tt/2wu84hk

Four PTEN-targeting co-expressed miRNAs and ACTN4-targeting miR-548b are independent prognostic biomarkers in human squamous cell carcinoma of the oral tongue

Abstract

The purpose of this study was to determine the prognostic value and oncogenic pathways associated to miRNA expression in squamous cell carcinoma of the oral tongue and to link these miRNA candidates with potential gene targets. We performed a miRNA screening within our institutional cohort (n = 58 patients) and reported five prognostic targets including a cluster of four co-expressed miRNAs (miR-18a, miR-92a, miR-103, and miR-205). Multivariate analysis showed that expression of miR-548b (p = 0.007) and miR-18a (p = 0.004, representative of co-expressed miRNAs) are independent prognostic markers for squamous cell carcinoma of the oral tongue. These findings were validated in The Cancer Genome Atlas (TCGA) cohort (n=131) for both miRNAs (miR-548b: p = 0.027; miR-18a: p = 0.001). Bioinformatics analysis identified PTEN and ACTN4 as direct targets of the four co-expressed miRNAs and miR-548b, respectively. Correlations between the five identified miRNAs and their respective targeted genes were validated in the two merged cohorts and were concordantly significant (miR-18a/PTEN: p < 0.0001; miR-92a/PTEN: p = 0.0008; miR-103/PTEN: p = 0.008; miR-203/PTEN: p = 0.019; miR-548b/ACTN4: p = 0.009). This article is protected by copyright. All rights reserved.

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TARGETING RNA-POLYMERASE I IN BOTH CHEMOSENSITIVE AND CHEMORESISTANT POPULATIONS IN EPITHELIAL OVARIAN CANCER

Purpose: A hallmark of neoplasia is increased ribosome biogenesis, and targeting this process with RNA polymerase I (Pol I) inhibitors has shown some efficacy.  We examined the contribution and potential targeting of ribosomal machinery in chemotherapy resistant and sensitive models of ovarian cancer.<br /><br />Experimental Design: Pol I machinery expression was examined, and subsequently targeted with the Pol I inhibitor CX-5461, in ovarian cancer cell lines, an immortalized surface epithelial line, and patient derived xenograft (PDX) models with and without chemotherapy.  Effects on viability, Pol I occupancy of rDNA, ribosomal content, and chemosensitivity were examined.<br /><br />Results: In PDX models, ribosomal machinery components were increased in chemotherapy-treated tumors compared to controls. 13 cell lines were sensitive to CX-5461, with IC50s 25nM - 2μM.  Interestingly two chemoresistant lines were 10.5- and 5.5-fold more sensitive than parental lines  . CX-5461 induced DNA damage checkpoint activation and G2/M arrest with increased H2AX staining.  Chemoresistant cells had 2-4-fold increased rDNA Pol I occupancy and increased rRNA synthesis, despite having slower proliferation rates, while ribosome abundance and translational efficiency were not impaired.  In five PDX models treated with CX-5461, one showed a complete response, one a 55% reduction in tumor volume, and one maintained stable disease for 45 days. <br />   <br />Conclusions: Pol I inhibition with CX-5461 shows high activity in ovarian cancer cell lines and PDX models, with an enhanced effect on chemoresistant cells. Effects occur independent of proliferation rates or dormancy. This represents a novel therapeutic approach that may have preferential activity in chemoresistant populations.

http://ift.tt/2vyZEb2

Phytochemical investigation and nephroprotective potential of Sida cordata in rat

Plants are an efficient source of natural antioxidant against free radicals causing kidney damages. Sida cordata ethyl acetate fraction has been reported for strong in vitro antioxidant potency, previously. In th...

http://ift.tt/2wu1KX4

Acute and sub-acute toxicity study of a Pakistani polyherbal formulation

Herbology is the prevailing system among the nationally-accepted alternative or complementary systems of medicine. The system is due to its general and patient-oriented methodology, is widely used in the gener...

http://ift.tt/2vATg3X

FOXA1-Dependent Enhancer Reprogramming Promotes Metastasis [Research Watch]

Recurrent enhancer changes accompany the metastatic transition in pancreatic cancer models.

http://ift.tt/2wtPben

Disrupting the APC-Asef Interaction Suppresses Cancer Cell Migration [Research Watch]

Structure-based design yields peptidomimetic APC–ARM pocket inhibitors that block Asef binding.

http://ift.tt/2vB7ORa

Fusobacterium nucleatum Promotes Autophagy-Mediated Chemoresistance [Research Watch]

Abundant F. nucleatum is associated with disease recurrence in patients with colorectal cancer.

http://ift.tt/2wtT6rg

PTPN2 Loss Sensitizes Tumor Cells to Immunotherapy [Research Watch]

Ptpn2 loss increases tumor cell IFN signaling to enhance antigen presentation and antitumor immunity.

http://ift.tt/2vyOlQ9

Why First-Line Nivolumab Is No Better than Chemo [News in Brief]

Patient selection could explain disparate results in recent NSCLC trials.

http://ift.tt/2ua1JXh

Neratinib Approved for HER2+ Breast Cancer [News in Brief]

Now an option for early-stage disease, but drug has modest survival benefit and some concerning side effects.

http://ift.tt/2vyVTCv

Core Regulatory Circuitries Mediate Neuroblastoma Heterogeneity [Research Watch]

Sympathetic noradrenergic and NCC-like transcriptional networks promote neuroblastoma heterogeneity.

http://ift.tt/2u9K7uQ

The effectiveness of advance care planning in improving end of life outcomes for people with dementia and their carers: A systematic review and critical discussion

End of life care for people with dementia can be poor, involving emergency hospital admissions, burdensome treatments of uncertain value and under-treatment of pain and other symptoms. Advance care planning (ACP) is identified, in England and elsewhere, as a means of improving end of life outcomes for people with dementia and their carers.

http://ift.tt/2vysYyi

Beyond simple planning: existential dimensions of conversations with patients at risk of dying from heart failure

Despite the recent promotion of communication guides to improve decision-making with patients nearing the end of their lives, these conversations remain challenging. Deeper and more comprehensive understanding of communication barriers that undermine discussions and decisions with patients at risk of dying from heart failure (HF) are vital for informing communication in healthcare.

http://ift.tt/2u9IvkG

Modulation of cholinergic, monoaminergic, and purinergic enzymes of the brain functions by bitter ( Vernonia amygdalina ) and water bitter ( Struchium sparganophora ) leaves extracts: comparison of phenolic constituents versus nootropic potentials

Abstract

This study investigated the possible neuroprotective properties of two commonly consumed tropical vegetables. The modulatory effects of Vernonia amygdalina (VA) and Struchium sparganophora (SS) on the activities of Na⁺/K⁺ ATPase, ecto-5′-nucleotidase, monoamine oxidase (MAO), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and FeSO₄-induced oxidative stress in rat brain homogenate were assessed. The result revealed that both vegetables inhibited AChE, BChE, MAO, and ecto-5'nucleotidase activities, but stimulated Na⁺/K⁺ ATPase activity in a concentration-dependent manner. The SS had a significantly higher (P ˂ 0.05) inhibitory effect on AChE (IC₅₀ = 4.83 μg/mL), BChE (IC₅₀ = 5.61 μg/mL), MAO (IC₅₀ = 26.11 μg/mL), ecto-5′ nucleotidase (IC₅₀ = 23.04 μg/mL) than VA [AChE (IC₅₀ = 7.53 μg/mL), BChE (IC₅₀ = 7.32 μg/mL), MAO (IC₅₀ = 26.11 μg/mL), and ecto-5′ nucleotidase (IC₅₀ = 42.35 μg/mL)]. Furthermore, SS (IC₅₀ = 28.30 μg/mL) had a significantly higher (P < 0.05) stimulatory effect on Na⁺/K⁺ ATPase activity than VA (IC₅₀ = 34.87 μg/mL). Both extracts exhibited a strong antioxidant properties as typified by their radicals (OH and DPPH) scavenging and Fe²⁺ chelating abilities, as well as inhibition of Fe²⁺-induced lipid peroxidation in rat brain homogenate. The HPLC fingerprint of VA and SS extracts revealed the presence of catechin, chlorogenic acid, caffeic acid, p-coumaric acid, rutin, orientin, quercitrin quercetin, and luteolin. The stimulation of Na⁺/K⁺ ATPase activity, inhibition of 5′-nucleotidase, AChE, BChE, and MAO activities as well as Fe²⁺-induced oxidative stress could be a possible mechanism through which VA and SS exerts neuroprotective properties.

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Balguti Kesaria Ayurvedic Medicine: FDA Warning - High Levels Of Lead

[Posted 08/04/2017] AUDIENCE: Consumers, Health Care Professionals ISSUE: The U.S. Food and Drug Administration is warning parents and caregivers not to use "Balguti Kesaria (or Kesaria Balguti) Ayurvedic Medicine" due to the risk of lead...

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The Gluten-Free Diet Epidemic: Socioeconomic Factors Predict Google Search Trends More Than Health Related Factors

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More sensitivity analysis of Share 35, HIV co-infection, delist, hospital cost on cost-effectiveness of DAAs for LT HCV patients

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Stereotactic Radiosurgery with or without Whole Brain Radiotherapy for Limited Brain Metastases: A Secondary Analysis of the NCCTG N0574 (Alliance) Randomized Controlled Trial

There are conflicting data regarding whether adjuvant whole brain radiotherapy (WBRT) improves survival among patients with 1-3 brain metastases and favorable prognostic factors. Our post-hoc analysis of the N0574 trial demonstrated that overall survival did not differ according to the use of WBRT among non-small cell lung cancer patients with favorable (p=0.63) or unfavorable (p=0.85) diagnosis-specific graded prognostic assessment scores. In patients with limited (1-3) brain metastases, stereotactic radiosurgery alone remains a preferred treatment approach.

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The differential diagnosis between pleural sarcomatoid mesothelioma and spindle cell/pleomorphic (sarcomatoid) carcinomas of the lung: Evidence-Based guidelines from the International Mesothelioma Panel and the MESOPATH National Reference Center

Immunohistochemistry is used to distinguish sarcomatoid malignant mesotheliomas (SMM) from spindle cell and pleomorphic carcinomas (SPC) but there are no guidelines on how to interpret cases that show overlapping or equivocal immunohistochemical findings. A systematic literature review of the immunophenotype of these lesions was performed and the experience with 587 SMM and 46 SPC at MESOPATH was collected. Data were analyzed with Comprehensive Meta-Analysis 2.0 software (Biostast, Englewood N.J.).

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Prognostic value of programmed death ligand 1, p53, and Ki-67 in patients with advanced stage colorectal cancer

Current prognostic indicators are ineffective for identifying advanced stage colorectal cancer (CRC) patients with high risk of recurrence after surgical resection. We investigated the prognostic value of p53, Ki-67, and programmed death ligand 1 (PD-L1) in 254 patients with stage II and III CRC. The expression of p53 was positive in 63% of cases. Up-regulation of p53 was associated with smaller tumor size (P=.001) and higher Ki-67 labeling index (LI) (P=.031). The tumor Ki-67 LI was high (≥ 20%) in 197 (78%) of the patients.

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Preservation of sputum samples with cetylpyridinium chloride (CPC) for tuberculosis cultures and Xpert MTB/RIF in a low-income country

Culture contamination with environmental bacteria is a major challenge in tuberculosis (TB) laboratories in hot and humid climate zones. We studied the effect of cetylpyridinium chloride (CPC) preservation on ...

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The invasome of Salmonella Dublin as revealed by whole genome sequencing

Salmonella enterica serovar Dublin is a zoonotic infection that can be transmitted from cattle to humans through consumption of contaminated milk and milk products. Outbreaks of human ...

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Risk factors associated with loss to follow-up from tuberculosis treatment in Tajikistan: a case-control study

There are very few studies on reasons for loss to follow-up from TB treatment in Central Asia. This study assessed risk factors for LTFU and compared their occurrence with successfully treated (ST) patients in...

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Compounded Curcumin Emulsion Product for Injection by ImprimisRx: FDA Investigation - Serious Adverse Events Associated with Use

Audience: Health Professional, Pharmacy [Posted 08/04/2017] ISSUE: Two patients administered infusions of curcumin (a component of the spice turmeric) compounded with  polyethylene glycol (PEG) 40 castor oil reportedly experienced immediate...

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Optimization of photochemical decomposition acetamiprid pesticide from aqueous solutions and effluent toxicity assessment by Pseudomonas aeruginosa BCRC using response surface methodology

Contamination of water resources by acetamiprid pesticide is considered one of the main environmental problems. The aim of this study was the optimization of acetamiprid removal from aqueous solutions by TiO2/Fe3

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The functional characteristics CCNI modulation of myeloid- derived suppressor cells in liver inflammation

Abstract

There is increasing awareness of the immunologic roles of liver mononuclear populations including myeloid-derived suppressor cells (MDSCs). We took advantage of a large well defined cohort of 148 patients with liver inflammation and 45 health controls to focus on the qualitative and quantitative characteristics of MDSCs. We investigated the frequency, phenotype and functional capacities of MDSCs using peripheral blood MDSCs in a cohort of 55 patients with PBC, 40 with AIH, 39 with CHB, 14 with NAFLD and 45 healthy controls, and thereafter a liver targeted determination in 27 PBC, 27 AIH, 20 CHB, 14 NAFLD and 6 controls. We thence focused on mechanisms of this expansion using PBC as an example using both UDCA naive and treated patients. HLA-DR^-/lowCD33⁺CD11b⁺CD14⁺CD15^- monocytic MDSCs were elevated in diseases characterized by liver inflammation compared to healthy controls. Using PBC as a focus there was a significant correlation between levels of circulating MDSCs and disease related biochemical markers (ALP, TBIL). Second, there were higher amounts of MDSCs in PBC patients that were responsive to UDCA. Third, MDSCs from PBC manifest potent immunosuppressive function. There was a significant correlation in the accumulation of hepatic MDSCs in the inflamed lesions of PBC with histological changes such as fibrosis. Lastly, CCN1, a highly expressed protein in impaired cholangiocytes and hepatocytes, contribute to MDSCs expansion and MDSC-inducible nitric oxide synthase (iNOS) associated immune suppression. In conclusion, CCN1 modulate expansion and suppressive function of MDSCs. Our data highlight the potential functions of CCN1 on MDSCs and suggest therapeutic implications in inflammatory liver diseases. This article is protected by copyright. All rights reserved.

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Sarcopenia in hiding: The risk and consequence of underestimating muscle dysfunction in NASH

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Up to one third of individuals with NAFLD will develop non-alcoholic steatohepatitis (NASH), which is associated with progression to cirrhosis and is rapidly becoming the leading indication for liver transplantation. Sarcopenia is defined as a progressive and generalized loss of skeletal muscle mass, strength and function. It is seen in up to 60% of patients with end-stage liver disease and portends a poor prognosis. Recent studies have shown sarcopenia is a novel risk factor for developing NAFLD.

Pathophysiological mechanisms relating sarcopenia and NASH may include insulin resistance (IR) and increased inflammation. IR leads to accumulation of triglycerides in both muscle tissue and the liver. It also exacerbates proteolysis and leads to muscle depletion. Chronic inflammation leads to liver injury and progression of fibrosis. The inflammatory milieu also stimulates protein catabolism. Viewing skeletal muscle as an endocrine organ that secretes various salutary myokines may help us understand its role in the development of steatosis. A better understanding of the pathophysiology will aid in developing physical and pharmacologic therapeutic interventions.

In this review, we will explore the complex inter-relationships between sarcopenia and NASH. We will discuss the impact of sarcopenia in patients with NASH and therapeutic options for the management of sarcopenia. This article is protected by copyright. All rights reserved.

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The contribution of health risk behaviours to excess mortality in American adults with chronic hepatitis C: A population cohort-study

ABSTRACT

BACKGROUND: In resource-rich countries, chronic hepatitis C (CHC) infection is associated with a sizeable excess mortality risk. The extent to which this is due to: (a) the biological sequelae of CHC infection, versus b) a high concomitant burden of health risk behaviours (HRBs), is unclear.

METHODS: We used data from the 1999-2010 US National-Health-and-Nutritional-Examination-Surveys (NHANES), which include detailed information on HRBs and CHC infection status. We calculated the prevalence of the five major HRBs – alcohol use; cigarette smoking, physical inactivity, unhealthy diet, and illicit drug use –according to CHC after adjusting for socio-demographic differences. Mortality status after survey interview was ascertained via linkage to the US National Death Index. To assess the contribution of HRBs to the excess mortality risk, we determined the all-cause mortality rate ratio (MRR) for individuals with CHC relative to individuals without, and then calculated the attenuation in this MRR following adjustment for HRBs.

RESULTS: This analysis included 27,468 adult participants of NHANES of which 363 tested positive for CHC. All HRBs were markedly more prevalent among individuals with CHC versus individuals without. CHC was associated with a 2.4-fold higher mortality rate after adjustment for socio-demographic factors (MRR:2.36;95%CI:1.60-3.49). Subsequent adjustment for all five HRBs attenuated this ratio by 50.7% to MRR:1.67(95%CI:1.14-2.44). Higher levels of attenuation (69.1%) were observed among individuals aged 45-70yrs, who form the target demographic for US birth cohort screening.

CONCLUSION: At least half the excess mortality risk for individuals with CHC in the US may be due to HRBs rather than CHC. The remedial response to hepatitis C must not neglect action on HRBs if it is to fully resolve the high mortality problem in this population. This article is protected by copyright. All rights reserved.

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Role of 2D Shear Wave Elastography in the Assessment Of Chronic Liver Diseases

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Compounded Curcumin Emulsion Product for Injection by ImprimisRx: FDA Investigation - Serious Adverse Events Associated with Use

Audience: Health Professional, Pharmacy [Posted 08/04/2017] ISSUE: Two patients administered infusions of curcumin (a component of the spice turmeric) compounded with  polyethylene glycol (PEG) 40 castor oil reportedly experienced immediate...

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In Melanoma, Personalized Treatment Vaccines Show Promise

Results of an early-phase trial showed that a treatment vaccine personalized to a specific patient's cancer generated a robust immune response against the cancer and may have helped to prevent it from returning.

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Off-duty paramedic saves man’s life at gym

Stephen Harris was touring the gym with his son when a man on an exercise machine collapsed

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Outcome after resection of Adrenocortical Carcinoma liver metastases: a retrospective study

Abstract

Background

Metastatic Adrenocortical Carcinoma (ACC) is a rare malignancy with a poor 5-year-survival rate (<15%). A surgical approach is recommended in selected patients if complete resection of distant metastasis can be achieved. To date there are only limited data on the outcome after surgical resection of hepatic metastases of ACC.

Methods

A retrospective analysis of the German Adrenocortical Carcinoma Registry was conducted. Patients with liver metastases of ACC but without extrahepatic metastases or incomplete tumour resection were included.

Results

Seventy-seven patients fulfilled these criteria. Forty-three patients underwent resection of liver metastases of ACC. Complete tumour resection (R0) could be achieved in 30 (69.8%). Median overall survival after liver resection was 76.1 months in comparison to 10.1 months in the 34 remaining patients with unresected liver metastases (p < 0.001). However, disease free survival after liver resection was only 9.1 months. Neither resection status (R0/R1) nor extent of liver resection were significant predictive factors for overall survival. Patients with a time interval to the first metastasis/recurrence (TTFR) of greater than 12 months or solitary liver metastases showed significantly prolonged survival.

Conclusions

Liver resection in the case of ACC liver metastases can achieve long term survival with a median overall survival of more than 5 years, but disease free survival is short despite metastasectomy. Time to recurrence and single versus multiple metastases are predictive factors for the outcome.

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Whole-genome analysis of human papillomavirus genotypes 52 and 58 isolated from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer

Abstract

Background

Human papillomavirus genotypes 52 and 58 (HPV52/58) are frequently detected in patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC) in East Asian countries including Japan. As with other HPV genotypes, HPV52/58 consist of multiple lineages of genetic variants harboring less than 10% differences between complete genome sequences of the same HPV genotype. However, site variations of nucleotide and amino acid sequences across the viral whole-genome have not been fully examined for HPV52/58. The aim of this study was to investigate genetic variations of HPV52/58 prevalent among Japanese women by analyzing the viral whole-genome sequences.

Methods

The entire genomic region of HPV52/58 was amplified by long-range PCR with total cellular DNA extracted from cervical exfoliated cells isolated from Japanese patients with CIN or ICC. The amplified DNA was subjected to next generation sequencing to determine the complete viral genome sequences. Phylogenetic analyses were performed with the whole-genome sequences to assign variant lineages/sublineages to the HPV52/58 isolates. The variability in amino acid sequences of viral proteins was assessed by calculating the Shannon entropy scores at individual amino acid positions of HPV proteins.

Results

Among 52 isolates of HPV52 (CIN1, n = 20; CIN2/3, n = 21; ICC, n = 11), 50 isolates belonged to lineage B (sublineage B2) and two isolates belonged to lineage A (sublineage A1). Among 48 isolates of HPV58 (CIN1, n = 21; CIN2/3, n = 19; ICC, n = 8), 47 isolates belonged to lineage A (sublineages A1/A2/A3) and one isolate belonged to lineage C. Single nucleotide polymorphisms specific for individual variant lineages were determined throughout the viral genome based on multiple sequence alignments of the Japanese HPV52/58 isolates and reference HPV52/58 genomes. Entropy analyses revealed that the E1 protein was relatively variable among the HPV52 isolates, whereas the E7, E4, and L2 proteins showed some variations among the HPV58 isolates.

Conclusions

Among the HPV52/58-positive specimens from Japanese women with CIN/ICC, the variant distributions were strongly biased toward lineage B for HPV52 and lineage A for HPV58 across histological categories. Different patterns of amino acid variations were observed in HPV52 and HPV58 across the viral whole-genome.

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Hypoglycemia After Initiation of Basal Insulin in Patients with Type 2 Diabetes in the United States: Implications for Treatment Discontinuation and Healthcare Costs and Utilization

Abstract

Introduction

Hypoglycemia and fear of hypoglycemia may contribute to basal insulin discontinuation, poor glycemic control, and increased healthcare burden in patients with type 2 diabetes (T2D). This study aimed to determine the impact of hypoglycemia soon after basal insulin initiation on treatment discontinuation and economic outcomes in patients with T2D.

Methods

Hypoglycemic events within 6 months of basal insulin initiation were identified using retrospective cohort data from patients with T2D, at least 18 years of age, initiated on basal insulin therapy in the Clinformatics™ Data Mart for Multiplan claims database from January 1, 2008, through August 31, 2012. Data were adjusted for baseline characteristics. Discontinuation was established for patients with 12-month follow-up data, while discontinuation risk was assessed in the extended analysis (6- to 24-month follow-up) by Cox regression analysis. Healthcare use and costs were determined.

Results

Of 55,608 patients, 4.5% experienced hypoglycemia within 6 months of basal insulin initiation. Patients with hypoglycemia were more likely to discontinue basal insulin within 12 months of initiation (79.0% vs. 74.2%; P < 0.001). Data, adjusted for baseline characteristics such as age, any baseline hypoglycemia, and use of oral antidiabetes drugs, showed that patients with hypoglycemia had a greater risk of discontinuation (hazard ratio 1.16; 95% confidence interval 1.03, 1.32; P = 0.0164), were more likely to have a hospitalization (41.0% vs. 24.3%; P < 0.001) or an ED visit (55.8% vs. 35.1%; P < 0.001), and had higher diabetes-related ($13,662 vs. $7506; P < 0.001) and all-cause ($30,719 vs. $19,079; P < 0.001) healthcare costs.

Conclusions

US patients with T2D who experienced hypoglycemia within 6 months of basal insulin initiation were more likely to discontinue treatment, accompanied by a greater healthcare burden.

Funding

Sanofi US, Inc.

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Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis

Objective

Primary sclerosing cholangitis (PSC) is a genetically complex, inflammatory bile duct disease of largely unknown aetiology often leading to liver transplantation or death. Little is known about the genetic contribution to the severity and progression of PSC. The aim of this study is to identify genetic variants associated with PSC disease progression and development of complications.

Design

We collected standardised PSC subphenotypes in a large cohort of 3402 patients with PSC. After quality control, we combined 130 422 single nucleotide polymorphisms of all patients—obtained using the Illumina immunochip—with their disease subphenotypes. Using logistic regression and Cox proportional hazards models, we identified genetic variants associated with binary and time-to-event PSC subphenotypes.

Results

We identified genetic variant rs853974 to be associated with liver transplant-free survival (p=6.07x10^–9). Kaplan-Meier survival analysis showed a 50.9% (95% CI 41.5% to 59.5%) transplant-free survival for homozygous AA allele carriers of rs853974 compared with 72.8% (95% CI 69.6% to 75.7%) for GG carriers at 10 years after PSC diagnosis. For the candidate gene in the region, RSPO3, we demonstrated expression in key liver-resident effector cells, such as human and murine cholangiocytes and human hepatic stellate cells.

Conclusion

We present a large international PSC cohort, and report genetic loci associated with PSC disease progression. For liver transplant-free survival, we identified a genome-wide significant signal and demonstrated expression of the candidate gene RSPO3 in key liver-resident effector cells. This warrants further assessments of the role of this potential key PSC modifier gene.

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HLA-DQ:gluten tetramer test in blood gives better detection of coeliac patients than biopsy after 14-day gluten challenge

Objective

Initiation of a gluten-free diet without proper diagnostic work-up of coeliac disease is a frequent and demanding problem. Recent diagnostic guidelines suggest a gluten challenge of at least 14 days followed by duodenal biopsy in such patients. The rate of false-negative outcome of this approach remains unclear. We studied responses to 14-day gluten challenge in subjects with treated coeliac disease.

Design

We challenged 20 subjects with biopsy-verified coeliac disease, all in confirmed mucosal remission, for 14 days with 5.7 grams per oral gluten daily. Duodenal biopsies were collected. Blood was analysed by multiplex assay for cytokine detection, and by flow cytometry using HLA-DQ:gluten tetramers.

Results

Nineteen participants completed the challenge. Villous blunting appeared at end of challenge in 5 of 19 subjects. Villous height to crypt depth ratio reduced with at least 0.4 concomitantly with an increase in intraepithelial lymphocyte count of at least 50% in 9 of 19 subjects. Interleukin-8 plasma concentration increased by more than 100% after 4 hours in 7 of 19 subjects. Frequency of blood CD4⁺ effector-memory gut-homing HLA-DQ:gluten tetramer-binding T cells increased by more than 100% on day 6 in 12 of 15 evaluated participants.

Conclusion

A 14-day gluten challenge was not enough to establish significant mucosal architectural changes in majority of patients with coeliac disease (sensitivity 25%–50%). Increase in CD4⁺ effector-memory gut-homing HLA-DQ:gluten tetramer-binding T cells in blood 6 days after gluten challenge is a more sensitive and less invasive biomarker that should be validated in a larger study.

Trial registration number

NCT02464150

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Nuclear orphan receptor NR2F6 as a safeguard against experimental murine colitis

Objective

Nuclear receptors are known to regulate both immune and barrier functions in the GI tract. The nuclear orphan receptor NR2F6 has been shown to suppress the expression of proinflammatory cytokines in T lymphocytes. NR2F6 gene expression is reduced in patients with IBS or UC, but its functional role and tissue dependency in healthy and inflamed gut have not yet been investigated.

Design

Intestinal inflammation was induced in wild-type, Nr2f6-deficient, Rag1-deficient or bone marrow-reconstituted mice by administration of chemical (dextran sodium sulfate (DSS)) and immunogenic (T cell transfer) triggers. Disease phenotypes were investigated by survival, body weight, colon length and analysis of immune cell infiltrates. Additionally, histology, intestinal permeability, tight junction proteins, bacterial fluorescence in situ hybridisation, apoptosis, cell proliferation and mucus production were investigated.

Results

Nr2f6-deficient mice were highly susceptible to DSS-induced colitis characterised by enhanced weight loss, increased colonic tissue destruction and immune cell infiltration together with enhanced intestinal permeability and reduced Muc2 expression. T cell transfer colitis and bone marrow reconstitution experiments demonstrated that disease susceptibility was not dependent on the expression of Nr2f6 in the immune compartment but on the protective role of NR2F6 in the intestinal epithelium. Mechanistically, we show that NR2F6 binds to a consensus sequence at –2 kb of the Muc2 promoter and transactivates Muc2 expression. Loss of NR2F6 alters intestinal permeability and results in spontaneous late-onset colitis in Nr2f6-deficient mice.

Conclusion

We have for the first time identified a fundamental and non-redundant role of NR2F6 in protecting gut barrier homeostasis.

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Gene expression profiling in uveal melanoma: technical reliability and correlation of molecular class with pathologic characteristics

A 15-gene expression profile test has been clinically validated and is widely utilized in newly diagnosed uveal melanoma (UM) patients to assess metastatic potential of the tumor. As most patients are treated ...

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Creation and Transplantation of an Adipose-derived Stem Cell (ASC) Sheet in a Diabetic Wound-healing Model

Adipose-derived stem cells (ASCs) are easily isolated and harvested from the fat of normal rats. ASC sheets can be created using cell-sheet engineering and can be transplanted into Zucker diabetic fatty rats exhibiting full-thickness skin defects with exposed bone and then covered with a bilayer of artificial skin.

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Merging the “Morphology–Performance–Fitness” Paradigm and Life-History Theory in the Eagle Lake Garter Snake Research Project

Abstract

The morphology–performance–fitness paradigm for testing selection on morphological traits has seen decades of successful application. At the same time, life-history approaches using matrix methods and perturbation studies have also allowed the direct estimate of selection acting on vital rates and the traits that comprise them. Both methodologies have been successfully applied to the garter snakes of the long-term Eagle Lake research project to reveal selection on morphology, such as color pattern, number of vertebrae, and gape size; and life-history traits such as birth size, growth rates, and juvenile survival. Here we conduct a reciprocal transplant study in a common laboratory environment to study selection on morphology and life-history. To place our results in the ecomorphology paradigm, we measure performance outcomes (feeding rates, growth, insulin-like growth factor 1 titers) of morphological variation (body size, condition) and their fitness consequences for juvenile survival—a trait that has large fitness sensitivities in these garter snake populations, and therefore is thought to be subject to strong selection. To better merge these two complementary theories, we end by discussing our findings in a nexus of morphology–performance–fitness–life history to highlight what these approaches, when combined, can reveal about selection in the wild.

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Predicting Life-History Trade-Offs with Whole-Organism Performance

Abstract

Whole-organism performance traits are key intermediaries between the organism and the environment. Because performance traits are energetically costly to both build and maintain, performance will compete with other life-history traits over a limited pool of acquired energetic resources at any given time, potentially leading to trade-offs in performance expression. Although these trade-offs can have important implications for organismal fitness we currently lack a conceptual framework for predicting both where trade-offs might be expected, and which traits may be especially prone to trade-offs with other fitness-related life-history traits. We propose such a framework based on an estimate of the energetic requirements of locomotion in vertebrates, the ecological cost of transport. By analyzing existing data on mammalian energetic budgets and life-history, we found that species with higher costs of locomotion also tended to be those with "slow" life histories that invest relatively less in current reproduction than "fast" life-history species. We discuss the potential implications of ectothermy for masking such relationships, and how this framework might be expanded upon in the future.

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The interplay of matrix metalloproteinase-8, transforming growth factor-β1 and vascular endothelial growth factor-C cooperatively contributes to the aggressiveness of oral tongue squamous cell carcinoma

The interplay of matrix metalloproteinase-8, transforming growth factor-β1 and vascular endothelial growth factor-C cooperatively contributes to the aggressiveness of oral tongue squamous cell carcinoma

British Journal of Cancer advance online publication, August 3 2017. doi:10.1038/bjc.2017.249

Authors: Pirjo Åström, Krista Juurikka, Elin S Hadler-Olsen, Gunbjørg Svineng, Nilva K Cervigne, Ricardo D Coletta, Juha Risteli, Joonas H Kauppila, Sini Skarp, Samuel Kuttner, Ana Oteiza, Meeri Sutinen & Tuula Salo

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Non-conventional role of haemoglobin beta in breast malignancy

Non-conventional role of haemoglobin beta in breast malignancy

British Journal of Cancer advance online publication, August 3 2017. doi:10.1038/bjc.2017.247

Authors: Marco Ponzetti, Mattia Capulli, Adriano Angelucci, Luca Ventura, Simona Delle Monache, Cinzia Mercurio, Alessia Calgani, Patrizia Sanità, Anna Teti & Nadia Rucci

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Randomised Phase 2 study of maintenance linsitinib (OSI-906) in combination with erlotinib compared with placebo plus erlotinib after platinum-based chemotherapy in patients with advanced non-small cell lung cancer

Randomised Phase 2 study of maintenance linsitinib (OSI-906) in combination with erlotinib compared with placebo plus erlotinib after platinum-based chemotherapy in patients with advanced non-small cell lung cancer

British Journal of Cancer advance online publication, August 3 2017. doi:10.1038/bjc.2017.226

Authors: Tudor-Eliade Ciuleanu, Samreen Ahmed, Joo-Hang Kim, Jörg Mezger, Keunchil Park, Michael Thomas, Jihong Chen, Srinivasu Poondru, Jan M VanTornout, Debbie Whitcomb & Fiona Blackhall

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The inflammatory potential of diet and ovarian cancer risk: results from two prospective cohort studies

The inflammatory potential of diet and ovarian cancer risk: results from two prospective cohort studies

British Journal of Cancer advance online publication, August 3 2017. doi:10.1038/bjc.2017.246

Authors: Fred K Tabung, Tianyi Huang, Edward L Giovannucci, Stephanie A Smith-Warner, Shelley S Tworoger & Elizabeth M Poole

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Reply to ‘Comment on ‘Transarterial chemo-embolisation of hepatocellular carcinoma: impact of liver function and vascular invasion’ ’

Reply to 'Comment on 'Transarterial chemo-embolisation of hepatocellular carcinoma: impact of liver function and vascular invasion' '

British Journal of Cancer advance online publication, August 3 2017. doi:10.1038/bjc.2017.241

Authors: Iman Waked & Philip J Johnson

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Choosing wisely: a model-based analysis evaluating the trade-offs in cancer benefit and diagnostic referrals among alternative HPV testing strategies in Norway

Choosing wisely: a model-based analysis evaluating the trade-offs in cancer benefit and diagnostic referrals among alternative HPV testing strategies in Norway

British Journal of Cancer advance online publication, August 3 2017. doi:10.1038/bjc.2017.248

Authors: Emily A Burger, Kine Pedersen, Stephen Sy, Ivar Sønbø Kristiansen & Jane J Kim

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Diagnostic value of CA19.9, circulating tumour DNA and circulating tumour cells in patients with solid pancreatic tumours

Diagnostic value of CA19.9, circulating tumour DNA and circulating tumour cells in patients with solid pancreatic tumours

British Journal of Cancer advance online publication, August 3 2017. doi:10.1038/bjc.2017.250

Authors: David Sefrioui, France Blanchard, Emmanuel Toure, Paul Basile, Ludivine Beaussire, Claire Dolfus, Anne Perdrix, Marianne Paresy, Michel Antonietti, Isabelle Iwanicki-Caron, Raied Alhameedi, Stephane Lecleire, Alice Gangloff, Lilian Schwarz, Florian Clatot, Jean-Jacques Tuech, Thierry Frébourg, Fabrice Jardin, Jean-Christophe Sabourin, Nasrin Sarafan-Vasseur, Pierre Michel & Frédéric Di Fiore

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