bluuebunny/crossref_metadata_2025 huggingface dataset:
Statin-associated muscle symptoms (SAMS) in primary prevention for cardiovascular disease in older adults: a protocol for a systematic review and meta-analysis of randomised controlled trials
Authors: Zhou Zhen , Albarqouni Loai , Breslin Monique , Curtis Andrea J , Nelson Mark
Published: September 2017

Introduction

Although statins are commonly used for prevention of cardiovascular disease, there is limited evidence about statin-related adverse effects in older people. Statin-related adverse events (AEs), especially the statin-associated muscle symptoms (SAMS), are the most common reasons for their discontinuation. Therefore, it is important to determine the risk of SAMS in the older population. We will undertake a systematic review and meta-analysis primarily focusing on the risk of SAMS and secondarily targeting myopathy, rhabdomyolysis, AEs and serious AEs, dropouts due to SAMS in run-in period, related permanent discontinuation rate of statins and creatine kinase level, among older people who received statins for primary prevention.

Methods and analysis

This study has been developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols statement. We will include randomised controlled trials in which statin was compared with placebo with at least 1 year follow-up among older adults aged ≥65. This review is an update of a Cochrane systematic review that included the articles published before 2012. Cochrane Central Register of Controlled Trials, Medline OvidSP and Embase electronic database searches will be performed to identify relevant articles, limiting the publication date from 1 January 2012 to 13 February 2017. There will be no language limitation. Two independent reviewers will screen titles and abstracts and full text in duplicate. Risk of bias and evidence quality will be assessed using the Cochrane Collaboration’s tool and the Grading of Recommendations Assessment, Development and Evaluation approach, respectively. A meta-analysis using pooled data will be undertaken, if appropriate. We will also perform metaregression and subgroup analyses to identify sources of heterogeneity.

Ethics and dissemination

This study is exempt from ethics approval due to the anonymous and aggregated data used. The outcomes will be disseminated by conference presentations and published in a peer-reviewed journal.

Trial registration number

CRD42017058436.
Why involve families in acute mental healthcare? A collaborative conceptual review
Authors: Dirik Aysegul , Sandhu Sima , Giacco Domenico , Barrett Katherine , Bennison Gerry , Collinson Sue , Priebe Stefan
Published: September 2017

Objectives

Family involvement is strongly recommended in clinical guidelines but suffers from poor implementation. To explore this topic at a conceptual level, a multidisciplinary review team including academics, clinicians and individuals with lived experience undertook a review to explore the theoretical background of family involvement models in acute mental health treatment and how this relates to their delivery.

Design

A conceptual review was undertaken, including a systematic search and narrative synthesis. Included family models were mapped onto the most commonly referenced underlying theories: the diathesis–stress model, systems theories and postmodern theories of mental health. Common components of the models were summarised and compared. Lastly, a thematic analysis was undertaken to explore the role of patients and families in the delivery of the approaches.

Setting

General adult acute mental health treatment.

Results

Six distinct family involvement models were identified: Calgary Family Assessment and Intervention Models, ERIC (Equipe Rapide d’Intervention de Crise), Family Psychoeducation Models, Family Systems Approach, Open Dialogue and the Somerset Model. Findings indicated that despite wide variation in the theoretical models underlying family involvement models, there were many commonalities in their components, such as a focus on communication, language use and joint decision-making. Thematic analysis of the role of patients and families identified several issues for implementation. This included potential harms that could emerge during delivery of the models, such as imposing linear ‘patient–carer’ relationships and the risk of perceived coercion.

Conclusions

We conclude that future staff training may benefit from discussing the chosen family involvement model within the context of other theories of mental health. This may help to clarify the underlying purpose of family involvement and address the diverse needs and world views of patients, families and professionals in acute settings.
Does public transport use prevent declines in walking speed among older adults living in England? A prospective cohort study
Authors: Rouxel Patrick , Webb Elizabeth , Chandola Tarani
Published: September 2017

Objectives

Although there is some evidence that public transport use confers public health benefits, the evidence is limited by cross-sectional study designs and health-related confounding factors. This study examines the effect of public transport use on changes in walking speed among older adults living in England, comparing frequent users of public transport to their peers who did not use public transport because of structural barriers (poor public transport infrastructure) or through choice.

Design

Prospective cohort study.

Setting

England, UK.

Participants

Older adults aged ≥60 years eligible for the walking speed test. 6246 individuals at wave 2 (2004–2005); 5909 individuals at wave 3 (2006–2007); 7321 individuals at wave 4 (2008–2009); 7535 individuals at wave 5 (2010–2011) and 7664 individuals at wave 6 (2012–2013) of the English Longitudinal Study of Ageing.

Main outcome measure

The walking speed was estimated from the time taken to walk 2.4 m. Fixed effects models and growth curve models were used to examine the associations between public transport use and walking speed.

Results

Older adults who did not use public transport through choice or because of structural reasons had slower walking speeds (−0.02 m/s (95% CI −0.03 to –0.003) and −0.02 m/s (95% CI −0.03 to –0.01), respectively) and took an extra 0.07 s to walk 2.4 m compared with their peers who used public transport frequently. The age-related trajectories of decline in walking speed were slower for frequent users of public transport compared with non-users.

Conclusions

Frequent use of public transport may prevent age-related decline in physical capability by promoting physical activity and lower limb muscle strength among older adults. The association between public transport use and slower decline in walking speed among older adults is unlikely to be confounded by health-related selection factors. Improving access to good quality public transport could improve the health of older adults.
Characteristics of patients included and enrolled in studies on the prognostic value of serum biomarkers for prediction of postconcussion symptoms following a mild traumatic brain injury: a systematic review
Authors: Mercier Eric , Tardif Pier-Alexandre , Emond Marcel , Ouellet Marie-Christine , de Guise Élaine , Mitra Biswadev , Cameron Peter , Le Sage Natalie
Published: September 2017

Objective

Mild traumatic brain injury (mTBI) has been insufficiently researched, and its definition remains elusive. Investigators are confronted by heterogeneity in patients, mechanism of injury and outcomes. Findings are thus often limited in generalisability and clinical application. Serum protein biomarkers are increasingly assessed to enhance prognostication of outcomes, but their translation into clinical practice has yet to be achieved. A systematic review was performed to describe the adult populations included and enrolled in studies that evaluated the prognostic value of protein biomarkers to predict postconcussion symptoms following an mTBI.

Data sources

Searches of MEDLINE, Embase, CENTRAL, CINAHL, Web of Science, PsycBITE and PsycINFO up to October 2016.

Data selection and extraction

Two reviewers independently screened for potentially eligible studies, extracted data and assessed the overall quality of evidence by outcome using the Grading of Recommendations Assessment, Development and Evaluation approach.

Results

A total of 23 298 citations were obtained from which 166 manuscripts were reviewed. Thirty-six cohort studies (2812 patients) having enrolled between 7 and 311 patients (median 89) fulfilled our inclusion criteria. Most studies excluded patients based on advanced age (n=10 (28%)), neurological disorders (n=20 (56%)), psychiatric disorders (n=17 (47%)), substance abuse disorders (n=13 (36%)) or previous traumatic brain injury (n=10 (28%)). Twenty-one studies (58%) used at least two of these exclusion criteria. The pooled mean age of included patients was 39.3 (SD 4.6) years old (34 studies). The criteria used to define a mTBI were inconsistent. The most frequently reported outcome was postconcussion syndrome using the Rivermead Post-Concussion Symptoms Questionnaire (n=18 (50%)) with follow-ups ranging from 7 days to 5 years after the mTBI.

Conclusions

Most studies have recruited samples that are not representative and generalisable to the mTBI population. These exclusion criteria limit the potential use and translation of promising serum protein biomarkers to predict postconcussion symptoms.
Differences in experiences of care between patients diagnosed with metastatic cancer of known and unknown primaries: mixed-method findings from the 2013 cancer patient experience survey in England
Authors: Wagland Richard , Bracher Mike , Drosdowsky Allison , Richardson Alison , Symons John , Mileshkin Linda , Schofield Penny
Published: September 2017

Objectives

To explore differences in experiences of care reported in the Cancer Patient Experience Survey (CPES) between patients with cancer of unknown primary (CUP) and those with metastatic disease of known primary (non-CUP); to determine insights pertaining to the experiences of care for CUP respondents from free-text comments.

Design

Two separate, but related, studies, involving secondary analysis of existing data. Using frequency matching of CUP and non-CUP patients, statistical comparisons of responses to CPES questions were conducted. Free-text comments from CUP respondents were analysed thematically.

Setting and participants

The CPES questionnaire comprises 63 closed questions measuring 8 areas that relate to experience of care and 3 free-text questions. Questionnaires were mailed to all adult patients (aged ≥16 years) in England with cancer admitted to hospital between 1 September 2013 and 30 November 2013.

Results

Matched analysis of closed response items from 2992 patients found significant differences between CUP (n=1496) and non-CUP patients (n=1496): CUP patients were more likely to want more written information about their type of cancer and tests received, to receive their diagnosis from a general practitioner (GP) and have seen allied health professionals, but less likely to have understood explanations of their condition or had surgery. Freetext responses (n=3055) were coded into 17 categories and provided deeper insight regarding patient information and interactions with GPs. CPES data may include a preponderance of patients with favourable CUP subtypes and patients initially identified as CUP but whose primary was subsequently identified.

Conclusions

These are the first large-scale studies to explore the experiences of care of CUP patients. The significant differences identified between the experiences of CUP and non-CUP patients suggest CUP patients require more psychosocial support and specific interventions to manage diagnostic uncertainty and the multiple investigations many CUP patients face. Substantial limitations were identified with the CPES data, emphasising the need for prospective studies.
A national survey exploring oral healthcare service provision across Australian community pharmacies
Authors: Freeman Christopher R , Abdullah Nabilah , Ford Pauline J , Taing Meng-Wong
Published: September 2017

Objectives

This study investigated pharmacists’ and pharmacy assistants’ current practices and perspectives with regard to oral healthcare provision across Australian community pharmacies.

Design

Cross-sectional study. A questionnaire for each pharmacist and pharmacy assistant cohort was developed and administered by online or postal means. Pearson’s χ2test was used to examine relationships between categorical variables.

Participants

Pharmacists and pharmacy assistants working within 2100 randomly selected Australian community pharmacies.

Results

The overall response rate was 58.5% (644/1100) for the pharmacist cohort and 28% (280/1000) for the pharmacy assistant cohort. This represents pharmacy staff responses from 803 community pharmacies across Australia (approximately 14.6%, 803/5500 of community pharmacies nationally). Overall, the majority of pharmacists (80.2%; 516/644) and pharmacy assistants (83.6%; 234/280) reported providing oral health advice/consultations to health consumers up to five times each week. More than half of community pharmacists and pharmacy assistants were involved in identifying signs and symptoms for oral health problems; and the majority believed health consumers were receptive to receiving oral health advice. Additionally, more than 80% of pharmacists and 60% of pharmacy assistants viewed extended oral healthcare roles positively and supported integrating them within their workplace; extended roles include provision of prevention, early intervention and referral to oral healthcare services. The most commonly reported barriers to enhance pharmacy staff involvement in oral healthcare within Australian community pharmacies include lack of knowledge, ongoing training and resources to assist practice.

Conclusion

This study highlights that Australian pharmacists have an important role in oral health and provides evidence supporting the need for growing partnerships/collaborations between pharmacy and dental healthcare professionals and organisations to develop, implement and evaluate evidence-based resources, interventions and services to deliver improved and responsive oral healthcare within Australian communities.
REducing STEroids in Relapsing Nephrotic syndrome: the RESTERN study— protocol of a national, double-blind, randomised, placebo-controlled, non-inferiority intervention study
Authors: Schijvens A M , Dorresteijn E M , Roeleveld N , ter Heine R , van Wijk J A E , Bouts A H M , Keijzer-Veen M G , van de Kar N C A J , van den Heuvel L P W J , Schreuder M F
Published: September 2017

Introduction

Oral corticosteroids are the first-line treatment for idiopathic childhood nephrotic syndrome. Most children experience several relapses, needing repeated courses of corticosteroid therapy. This exposes them to side effects and long-term complications. For most patients, long-term prognosis is for complete resolution of the disease over time and maintenance of normal kidney function. Therefore, it is vital to focus on minimising adverse events of the disease and its therapy. Unfortunately, no randomised controlled trials are available to determine the optimal corticosteroid treatment of an infrequent relapse of nephrotic syndrome. Recent studies show that treatment schedules for the first episode can safely be shortened to 2 months. The hypothesis of the REducing STEroids in Relapsing Nephrotic syndrome (RESTERN) study is that a 4-week reduction of alternate-day steroids after inducing remission is effective and safe, reduces steroid exposure by 35% on average and is therefore preferable.

Methods and analysis

The RESTERN study is a nationwide, double-blind, randomised, placebo-controlled, non-inferiority intervention study. Children aged 1–18 years with a relapse of steroid-sensitive nephrotic syndrome are eligible for this study. Study subjects (n=144) will be randomly assigned to either current standard therapy in the Netherlands or a reduced prednisolone schedule. The primary outcome of the RESTERN study is the time to first relapse after the final prednisolone dose. The secondary outcomes are the number or relapses, progression to frequent relapsing or steroid dependent nephrotic syndrome and the cumulative dosage of prednisolone during the study period.

Ethics and dissemination

This non-inferiority trial will be performed in accordance with the Declaration of Helsinki and has been approved by the medical ethical committee of Arnhem-Nijmegen and the Dutch Competent Authority (Central Committee on Research Involving Human Subjects, CCMO). After completion of this study, results will be published in national and international peer-reviewed scientific journals. Papers will be published according to CCMO guidelines. The final report will be made available to trial participants.

Trial registration number

NTR5670, EudraCT no 2016-002430-76.
Comparative analysis of the visual performance after implantation of the toric implantable collamer lens in stable keratoconus: a 4-year follow-up after sequential procedure (CXL+TICL implantation)
Authors: Doroodgar Farideh , Niazi Feazollah , Sanginabadi Azad , Niazi Sana , Baradaran-Rafii Alireza , Alinia Cyrus , Azargashb Eznollah , Ghoreishi Mohammad
Published: September 2017

Aims

To report on 4-year postoperative visual performance with the toric implantable collamer lens (TICL) for stable keratoconus after sequential procedure (corneal collagen crosslinking plus TICL implantation).

Methods

Forty eyes of 24 patients with stable keratoconus with myopia between 0.00 and −18.00 dioptres (D) and astigmatism between 1.25 and 8.00 D were evaluated in this prospective interventional study (https://clinicaltrials.gov/ct2/show/NCT02833649). We evaluated refraction, visual outcomes, astigmatic changes analysed by Alpins vector, contrast sensitivity, aberrometry, modulation transfer functions (MTFs), defocus curve, and operative and postoperative complications.

Results

At 4-year follow-up, 45% had 20/20 vision or better and 100% had 20/40 or better uncorrected visual acuity (UCVA). Vector analysis of refractive astigmatism shows that the surgically induced astigmatism (SIA) (3.20±1.46 D) was not significantly different from the target induced astigmatism (TIA) (3.14±1.42 D) (p=0.620). At 4 years postoperatively, none of the eyes showed a decrease in UCVA, in contrast to 24 eyes in which UCVA was increased by ≥1 lines, with contrast sensitivity and improvement in total aberrations and MTF value at 5 per degree (*p=0.004) after TICL implantation. The cumulative 4-year corneal endothelial cell loss was ≤5%. No patients reported dissatisfaction. At the end of follow-up, the vault was 658±54.33m (range, 500–711) and the intraocular pressure was 11.7±2.08 mm Hg. Occurrences of glare and night-driving troubles diminished after TICL surgery.

Conclusion

The results from this standardised clinical investigation support TICL implantation from clinical and optical viewpoints in patients with stable keratoconus.

Trial registration number

NCT02833649, Pre-results
High-intensity exercise training does not influence body weight but improves lipid oxidation in obese adults: a 6-week RCT
Authors: Jabbour Georges , Iancu Horia-Daniel
Published: September 2017

Objectives

This study examined the effects of 6 weeks of high-intensity training (HIT) on lipid oxidation (LO) rates during incremental exercises in obese adults.

Methods

Twenty-four obese adults were randomised into a no-exercise control group (n=12; body mass index=33.3 (4.8) kg.m−2) and a HIT group (18 sessions of 6×6 s of supramaximal cycling and 2 min passive intervals; n=12; body mass index=33.2 (2.8)kg.m−2). The percentage of LO contribution was computed at rest and for all workloads (25, 50, 75, 100 and 125 W) in both groups before and after training via a graded maximal cycling test.

Results

After training, the HIT group showed significantly higher LO at rest and at 25, 50 and 75 W compared with baseline (p<0.01) and the control group (p<0.01). Moreover, for the training group, the homoeostasis model assessment of insulin resistance (HOMA-IR) index decreased significantly from the baseline value (p<0.01) and the control group value (p<0.01). The increases in LO observed at rest and stages 25, 50 and 75 W were positively correlated with the declines in the HOMA-IR index (r=0.87, r=0.83, r=0.91 and r=0.88; p<0.01).

Conclusion

In obese adults, HIT increased lipid contributions to energy release at rest and in response to incremental exercise, while there were no changes in participants’ aerobic capacity. This supports the hypothesis that metabolic changes rather than improved aerobic capacity are important to improve LO.

Trial registration number

ISRCTN66508384. Stage: post-results.
Transradial access: lessons learned from cardiology
Authors: Snelling Brian M , Sur Samir , Shah Sumedh Subodh , Marlow Megan M , Cohen Mauricio G , Peterson Eric C
Published: September 2017

Innovations in interventional cardiology historically predate those in neuro-intervention. As such, studying trends in interventional cardiology can be useful in exploring avenues to optimise neuro-interventional techniques. One such cardiology innovation has been the steady conversion of arterial puncture sites from transfemoral access (TFA) to transradial access (TRA), a paradigm shift supported by safety benefits for patients. While neuro-intervention has unique anatomical challenges, the access itself is identical. As such, examining the extensive cardiology literature on the radial approach has the potential to offer valuable lessons for the neuro-interventionalist audience who may be unfamiliar with this body of work. Therefore, we present here a report, particularly for neuro-interventionalists, regarding the best practices for TRA by reviewing the relevant cardiology literature. We focused our review on the data most relevant to our audience, namely that surrounding the access itself. By reviewing the cardiology literature on metrics such as safety profiles, cost and patient satisfaction differences between TFA and TRA, as well as examining the technical nuances of the procedure and post-procedural care, we hope to give physicians treating complex cerebrovascular disease a broader data-driven understanding of TRA.
TREVO stent-retriever mechanical thrombectomy for acute ischemic stroke secondary to large vessel occlusion registry
Authors: Zaidat Osama O , Castonguay Alicia C , Nogueira Raul G , Haussen Diogo C , English Joey D , Satti Sudhakar R , Chen Jennifer , Farid Hamed , Borders Candace , Veznedaroglu Erol , Binning Mandy J , Puri Ajit , Vora Nirav A , Budzik Ron F , Dabus Guilherme , Linfante Italo , Janardhan Vallabh , Alshekhlee Amer , Abraham Michael G , Edgell Randall , Taqi Muhammad Asif , Khoury Ramy El , Mokin Maxim , Majjhoo Aniel Q , Kabbani Mouhammed R , Froehler Michael T , Finch Ira , Ansari Sameer A , Novakovic Roberta , Nguyen Thanh N
Published: September 2017

Background

Recent randomized clinical trials (RCTs) demonstrated the efficacy of mechanical thrombectomy using stent-retrievers in patients with acute ischemic stroke (AIS) with large vessel occlusions; however, it remains unclear if these results translate to a real-world setting. The TREVO Stent-Retriever Acute Stroke (TRACK) multicenter Registry aimed to evaluate the use of the Trevo device in everyday clinical practice.

Methods

Twenty-three centers enrolled consecutive AIS patients treated from March 2013 through August 2015 with the Trevo device. The primary outcome was deﬁned as achieving a Thrombolysis in Cerebral Infarction (TICI) score of ≥2b. Secondary outcomes included 90-day modified Rankin Scale (mRS), mortality, and symptomatic intracranial hemorrhage (sICH).

Results

A total of 634patients were included. Mean age was 66.1±14.8 years and mean baseline NIH Stroke Scale (NIHSS) score was 17.4±6.7; 86.7% had an anterior circulation occlusion. Mean time from symptom onset to puncture and time to revascularization were 363.1±264.5 min and 78.8±49.6 min, respectively. 80.3% achieved TICI ≥2b. 90-day mRS ≤2 was achieved in 47.9%, compared with 51.4% when restricting the analysis to the anterior circulation and within 6 hours (similar to recent AHA/ASA guidelines), and 54.3% for those who achieved complete revascularization. The 90-day mortality rate was 19.8%. Independent predictors of clinical outcome included age, baseline NIHSS, use of balloon guide catheter, revascularization, and sICH.

Conclusion

The TRACK Registry results demonstrate the generalizability of the recent thrombectomy RCTs in real-world clinical practice. No differences in clinical and angiographic outcomes were shown between patients treated within the AHA/ASA guidelines and those treated outside the recommendations.
A population-based incidence of M2 strokes indicates potential expansion of large vessel occlusions amenable to endovascular therapy
Authors: Rai Ansaar T , Domico Jennifer R , Buseman Chelsea , Tarabishy Abdul R , Fulks Daniel , Lucke-Wold Noelle , Boo SoHyun , Carpenter Jeffrey S
Published: September 2017

Background

M2 occlusions may result in poor outcomes and potentially benefit from endovascular therapy. Data on the rate of M2 strokes is lacking.

Methodology

Patients with acute ischemic stroke discharged over a period of 3 years from a tertiary level hospital in the ‘stroke belt’ were evaluated for M2 occlusions on baseline vascular imaging. Regional and national incidence was calculated from discharge and multicounty data.

Results

There were 2739 ICD-9 based AIS discharges. M2 occlusions in 116 (4%, 95% CI 3.5% to 5%) patients constituted the second most common occlusion site. The median National Institute of Health Stroke Scale (NIHSS) score was 12 (IQR 5–18). Good outcomes were observed in 43% (95% CI 34% to 53%), poor outcomes in 57% (95% CI 47% to 66%), and death occurred in 27% (95% CI 19% to 37%) of patients. Receiver operating characteristics curves showed the NIHSS to be predictive of outcomes (area under the curve 0.829, 95% CI 0.745 to 0.913, p<0.0001). An NIHSS score ≥9 was the optimal cut-off point for predicting poor outcomes (sensitivity 85.7%, specificity 67.4%). 71 (61%) patients had an NIHSS score ≥9 and 45 (39%) an NIHSS score <9. The rate of good-outcome was 22.6% for NIHSS score ≥9 versus 78.4% for NIHSSscore <9 (OR=0.08, 95% CI 0.03 to 0.21, p<0.0001). Mortality was 42% for NIHSS score ≥9 versus 2.7% for NIHSS score <9 (OR=26, 95% CI 3.3 to 202, p<0.0001). Infarct volume was 57 (±55.7) cm3for NIHSS score ≥9 versus 30 (±34)cm3for NIHSS score <9 (p=0.003). IV recombinant tissue plasminogen activator (rtPA) administered in 28 (24%) patients did not affect outcomes. The rate of M2 occlusions was 7 (95% CI 5 to 9)/100 000 people/year (3%, 95% CI 2% to 4%), giving an incidence of 21 176 (95% CI 15 282 to 29 247)/year. Combined with M1, internal carotid artery terminus and basilar artery, this yields a ‘large vessel occlusion (LVO)+M2’ rate of 31 (95% CI 26 to 35)/100 000 people/year and a national incidence of 99 227 (95% CI 84 004 to 112 005) LVO+M2 strokes/year.

Conclusion

M2 occlusions can present with serious neurological deficits and cause significant morbidity and mortality. Patients with M2 occlusions and higher baseline deficits (NIHSS score ≥9) may benefit from endovascular therapy, thus potentially expanding the category of acute ischemic strokes amenable to intervention.
Comparing different thrombectomy techniques in five large-volume centers: a ‘real world’ observational study
Authors: Hesse Amélie Carolina , Behme Daniel , Kemmling André , Zapf Antonia , Hokamp Nils Große , Frischmuth Isabelle , Maier Ilko , Liman Jan , Tsogkas Ioannis , Buhk Jan-Hendrik , Tran Julia , Fiehler Jens , Mpotsaris Anastasios , Schramm Peter , Berlis Ansgar , Knauth Michael , Psychogios Marios-Nikos
Published: September 2017

Background and purpose

Thrombectomy has become the standard of care for acute ischaemic stroke due to large vessel occlusion. Aim of this study was to compare the radiological outcomes and time metrics of the various thrombectomy techniques.

Methods

In this retrospective, multicenter study we analysed the data of 450 patients with occlusion of the anterior circulation, treated in five high-volume center from 2013 to 2016. The treatment techniques were divided in three categories: first-pass use of a large-bore aspiration-catheter; first-pass use of a stent-retriever; and primary combined approach (PCA) of an aspiration-catheter and stent-retriever. Primary endpoints were successful reperfusion and groin to reperfusion time. Secondary endpoints were the number of attempts and occurrence of emboli in new territory (ENT). The primary analysis was based on the intention to treat groups (ITT).

Results

The ITT-analysis showed significantly higher reperfusion rates, with 86% of successful reperfusion in the PCA-group compared with 73% in the aspiration group and 65% in the stent-retriever group. There was no significant difference in groin to reperfusion time regarding the used technique. The secondary analysis showed an impact of the technique on the number of attempts and the occurrence of ENTs. Lowest ENT rates and attempts were reported with the combined approach.

Conclusions

The combined first-pass deployment of a stent-retriever and an aspiration-catheter was the most effective technique for reperfusion of anterior circulation large vessel occlusion. Our results correlate with the latest single-centrere studies, reporting very high reperfusion rates with PCA variations.
Long term follow-up of bifurcation aneurysms treated with braided stent assisted coiling and complex T- and Y- stent constructs
Authors: Cheung Nicholas K , Chiu Albert HY , Cheung Andrew , Wenderoth Jason D
Published: September 2017

Background

Stent assisted coil embolization (SACE) of bifurcation aneurysms is challenging. Heterogeneous results have been achieved to date, but largely for laser cut stents. While braided stents offer multiple technical advantages, their long term efficacy has yet to be validated.

Objective

To report the first long term 18 month results for the durability of bifurcation aneurysms treated with braided stents.

Materials and methods

Over a 4 year period, 59 consecutive patients with 60 bifurcation aneurysms underwent elective braided SACE across three Australian neurovascular centers. 17 of these aneurysms underwent T- or Y-shaped stent constructs. All patients had immediate, 6 month and 18 month clinical and radiological follow-up. Radiological assessment was made on modified Raymond–Roy occlusion scores while clinical assessment was based on the modified Rankin Scale. Subgroup analysis of 17 aneurysms treated with multi-stent constructs was conducted.

Results

6 month follow-up data were available for 59 aneurysms and 18 month follow-up data for 58 aneurysms. Satisfactory aneurysm occlusion was achieved in 97% at inception and at 6 months, and 98% at 18 months. Good neurological outcomes were achieved in 95% at 18 months. Similar satisfactory results were achieved with the multi-stent construct cohort. Intraprocedural thromboembolic events were recorded in 5% and delayed events in 2%. Technical complications were found in 5%. All complication rate was 13%.

Conclusion

Braided SACE was safe, efficacious, and durable at the long term 18 month follow-up, including for multi-stent constructs. Preliminary results indicate favorable clinical and radiological outcomes compared with laser cut stents.
Significant reduction in hospital-acquired thrombosis: impact of national risk assessment and real-time feedback
Authors: Rowswell Huw Raymond , Nokes Timothy J C
Published: September 2017

Objective

Since 2010, National Health Service hospitals in England have been incentivised to risk assess for Venous Thromboembolism (VTE) in all adult patients admitted, using a national tool. We studied the impact of this, together with local real-time reporting of VTE events to senior clinicians, on cases of hospital-acquired thrombosis (HAT) diagnosed, since 2010.

Methods

This was an observational cohort study reviewing all cases of VTE diagnosed between January 2010 and December 2016 in a single teaching hospital. These were matched against the number of patients admitted to produce crude incidence rates per thousand admissions. Similarly, all cases associated with inadequate thromboprophylaxis (TP) measures were documented over the same period.

Results

By the end of 2010, with 70% compliance with VTE risk assessment, improving to 90% (the national target) early in 2011, there were 217 HAT events from 103 845 admissions. In 2016, there were 176 HAT events from 119 128 admissions, being a significant reduction, relative risk (RR) 0.718 (95% CI 0.589 to 0.875; p=0.001). In 2010, there were 50 of 217 HAT events associated with inadequate TP, falling to 7 of 176 in 2016, also a significant reduction, RR 0.140 (95% CI 0.065 to 0.300; p=0.0001).

Conclusions

National guidance on VTE prevention and mandatory risk assessment linked to local real-time reporting of VTE events are associated with significant reductions both in total HAT events and those associated with inadequate TP.
Influence of aromatase inhibitors therapy on the occurrence of rheumatoid arthritis in women with breast cancer: results from a large population-based study of the Italian Society for Rheumatology
Authors: Caprioli Marta , Carrara Greta , Sakellariou Garifallia , Silvagni Ettore , Scirè Carlo Alberto
Published: September 2017

Objectives

The purpose of this study was to evaluate the risk of developing rheumatoid arthritis (RA) in a population of patients with breast cancer treated with aromatase inhibitors (AIs) compared with tamoxifen.

Methods

Data were collected from the administrative healthcare database of Lombardy Region, Italy, from 2004 to 2013. This study follows a nested cohort design, including women with a diagnosis of breast cancer starting treatment with tamoxifen, anastrozole, exemestane or letrozole. The risk of RA related to the prescription of the different drugs was estimated by survival models for competing risks and the results are presented as hazard ratios (HRs) and 95% confidence intervals (95% CI), adjusted for age and cancer severity.

Results

Out of total 10 493 women with breast cancer with a median (IQR) age of 66 (57–74), 7533 (71.8%) started an active treatment with AIs or tamoxifen. In this subgroup a total of 113 new cases of RA developed during the 26 105.9 person-year of 10 186 exposure periods, including time varying exposures in the same patient. Using tamoxifen as reference category, AIs therapy was associated with an increased risk of RA (adjusted HR 1.62 (95%1.03–2.56)), in particular in patients receiving anastrozole, even after adjusting for age and level of neoplasia: (adjusted HR 1.75 (95%1.07–2.86)).

Conclusions

In a large population-based sample of women with breast cancer, exposure to AIs compared with tamoxifen is associated with a significantly increased risk of RA, which is not influenced by the cancer severity and the relationship of age with indication to specific drugs.
Identifying chronic heavy alcohol use in emergency general surgery patients: a pilot study
Authors: Matar Maher M , Jewett Brent , Fakhry Samir M , Wilson Dulaney A , Ferguson Pamela L , Anton Raymond F , Sakran Joseph V
Published: September 2017

Background

Chronic heavy alcohol (CHA) use has been associated with perioperative complications. Emergency general surgery (EGS) patients are not routinely screened for CHA. If screened, it is usually for hazardous use of alcohol, using a survey such as the Alcohol Use Disorders Identification Test (AUDIT). This study screened EGS patients for CHA use using serum carbohydrate-deficient transferrin (%dCDT) level, a biomarker that has been validated as an indicator for CHA use, as well as the AUDIT. The purpose of this study was to determine the percent of EGS patients with CHA (as indicated by elevated %dCDT), and the relationship between %dCDT and AUDIT. Secondary aims included comparing the characteristics of EGS patients with and without CHA use, and evaluating the association of CHA use with negative clinical outcomes.

Methods

EGS patients aged 21 and older admitted to the general surgery inpatient service of a tertiary hospital from July 2014 to June 2016 were invited to participate in this study. %dCDT levels above 1.7% were considered positive for CHA use, as were AUDIT scores ≥8.

Results

195 EGS patients were screened for inclusion and 91 (46.7%) agreed to participate. 14 (15.4%) were positive for hazardous alcohol use on AUDIT and 5 (5.5%) were positive for CHA by %dCDT. Positive predictive value of AUDIT for CHA was 21.4%. There was no correlation between positive scores on AUDIT and %dCDT.

Discussion

Identifying at risk patients early on in their hospital course may allow clinicians to institute treatments to mitigate and/or circumvent complications in such patients. This pilot study determined that 17.6% of participating EGS patients were positive for some type of alcohol misuse, but only 5.5% had CHA. Further research is needed to determine whether routine use of %dCDT would be beneficial in reducing perioperative complications in this patient population.

Level of evidence

III (diagnostic test).
Human‐directed aggressive behaviour as the main presenting sign in dogs subsequently diagnosed with diskospondylitis
Authors: Affenzeller Nadja , McPeake Kevin James , McClement Jamie , Zulch Helen
Published: September 2017

This is the first report of aggressive behaviour as the primary presenting sign in two dogs subsequently found to have chronic diskospondylitis, with neither dog showing other typical clinical signs of this condition. Mild signs of pain were elicited on physical examination in both dogs. Further medical investigation revealed signs indicative of chronic diskospondylitis (L7/S1) and treatment with analgesics and antibiotics was commenced. A marked improvement in behaviour was seen in both dogs when on treatment. Dog 1 stopped exhibiting unpredictable episodes of growling and biting when handled or approached and dog 2 stopped vocalising and occasional growling when handled or lifted. Gradual treatment withdrawal (dog 1 after six weeks and dog 2 after four weeks, respectively) caused a recurrence of behaviour signs thus further treatment was recommenced. Continued follow‐up over a year revealed the importance of long‐term use of analgesics to prevent behavioural deterioration when chronic lesions are present.
Osteomyelitis caused by β‐haemolytic Listeria species in a dog
Authors: Genain Marie‐Aude , Brioschi Valentina , Hare Cassia , Ortiz Ana , Herrtage M E
Published: September 2017

A 3.6‐year‐old neutered female labrador retriever was presented with one month’s history of left hindlimb lameness and a five‐day history of anorexia. A severe osteolytic and osteoproductive polyostotic bone lesion affecting the proximal aspect of the tibia and the distal aspect of the femur was seen on radiographs. Histopathological evaluation confirmed cellulitis, myositis, neutrophilic osteomyelitis and bone necrosis and culture revealed a pure growth of β‐haemolytic Listeria species. To the authors' knowledge this is the first report of osteomyelitis caused by Listeria species in a dog without any identified primary cause of infection.
Reduced Expression of VAMP8 in Lacrimal Gland Affected by Chronic Graft-versus-Host Disease
Authors: Fukui Masaki , Ogawa Yoko , Mukai Shin , Kamoi Mizuka , Asato Teru , Kawakami Yutaka , Tsubota Kazuo
Published: September 2017

Purpose. To investigate whether the SNARE protein vesicle-associated membrane protein 8 (VAMP8) was implicated in the development of chronic ocular graft-versus-host disease (GVHD). Methods. Firstly, the chronic GVHD (cGVHD) and Sjögren’s syndrome (SS)-impaired lacrimal gland (LG) tissue sections from humans for diagnostic purpose were evaluated for VAMP8 expression by histopathology and immunohistochemistry. Next, serial changes of tear secretion and VAMP8 expression at both protein and mRNA level of LG in an animal cGVHD model compared with the syngeneic control. Results. Decreased VAMP 8 expression in the cGVHD-affected human LG was detected in comparison with SS-affected LG. Tear secretion in the murine cGVHD model was significantly reduced compared with that in the syngeneic controls 8 weeks after BMT. Protein expression of VAMP8 in the cGVHD-affected LG in murine cGVHD was decreased in comparison with that in the controls. Gene expression of VAMP8 in the cGVHD-affected murine LG was significantly less than that in the syngeneic control 3 weeks after BMT. Conclusions. Our results suggested that expression of VAMP8 in the cGVHD-affected LG was decreased and accordingly tear secretion in cGVHD was reduced. Collectively, the reduction of VAMP8 expression in the cGVHD-affected LG can be involved in the pathogenic processes of cGVHD-induced dry eye disease.
Mutation Spectrum Induced by 8‐Bromoguanine, a Base Damaged by Reactive Brominating Species, in Human Cells
Authors: Shinmura Kazuya , Kato Hisami , Goto Masanori , Tao Hong , Inoue Yusuke , Nakamura Satoki , Yoshida Haruki , Tsuzaki Emi , Sugimura Haruhiko
Published: September 2017

To date, the types of mutations caused by 8‐bromoguanine (8BrG), a major base lesion induced by reactive brominating species during inflammation, in human cells and the 8BrG repair system remain largely unknown. In this study, we performed a supF forward mutation assay using a shuttle vector plasmid containing a single 8BrG in three kinds of human cell lines and revealed that 8BrG in DNA predominantly induces a G → T mutation but can also induce G → C, G → A, and delG mutations in human cells. Next, we tested whether eight kinds of DNA glycosylases (MUTYH, MPG, NEIL1, OGG1, SMUG1, TDG, UNG2, and NTHL1) are capable of repairing 8BrG mispairs with any of the four bases using a DNA cleavage activity assay. We found that both the SMUG1 protein and the TDG protein exhibit DNA glycosylase activity against thymine mispaired with 8BrG and that the MUTYH protein exhibits DNA glycosylase activity against adenine mispaired with 8BrG. These results suggest that 8BrG induces some types of mutations, chiefly a G → T mutation, in human cells, and some DNA glycosylases are involved in the repair of 8BrG.
Upregulation of FBXW7 Suppresses Renal Cancer Metastasis and Epithelial Mesenchymal Transition
Authors: Cai Yangke , Zhang Meng , Qiu Xiaofu , Wang Bingwei , Fu Yu , Zeng Jun , Bai Jian , Yang Guosheng
Published: September 2017

Background and Objective. FBXW7, known as a general tumor suppressor, is commonly lowly expressed in metastatic malignancies. We aim to investigate the potential influence of FBXW7 overexpression on renal cell carcinoma (RCC) metastasis. Methods. We employed quantitative real-time PCR (qRT-PCR) and Western blotting (WB) to quantify the FBXW7 expression in RCC cell lines. Upregulation of FBXW7 was performed in vitro on RCC cells using the lentivirus covering coding region FBXW7 cDNA sequence, and functional tests were performed to verify FBXW7 overexpression on migration and invasion of RCC cells. Moreover, WB was employed to determine the expressions of MMP-2, MMP-9, and MMP-13, as well as EMT markers in the transfected RCC cells. Results. FBXW7 was significantly downregulated in RCC cell lines, dominated by 786-O and ACHN, when compared to normal renal cell line HK-2. Moreover, upregulation of FBXW7 in 786-O and ACHN cell lines significantly inhibited cell migration and invasion, as well as EMT. Present study also showed that FBXW7 was involved in the migration and invasion of RCC cells via regulating the expressions of MMP-2, MMP-9, and MMP-13. Conclusion. Our findings demonstrate that upregulation of FBXW7 inhibits RCC metastasis and EMT. FBXW7 is a potential therapeutic target for RCC patients.
mTOR and HDAC Inhibitors Converge on the TXNIP/Thioredoxin Pathway to Cause Catastrophic Oxidative Stress and Regression of RAS-Driven Tumors
Authors: Malone Clare F. , Emerson Chloe , Ingraham Rachel , Barbosa William , Guerra Stephanie , Yoon Haejin , Liu Lin L. , Michor Franziska , Haigis Marcia , Macleod Kay F. , Maertens Ophélia , Cichowski Karen
Published: September 2017

Although agents that inhibit specific oncogenic kinases have been successful in a subset of cancers, there are currently few treatment options for malignancies that lack a targetable oncogenic driver. Nevertheless, during tumor evolution cancers engage a variety of protective pathways, which may provide alternative actionable dependencies. Here, we identify a promising combination therapy that kills NF1-mutant tumors by triggering catastrophic oxidative stress. Specifically, we show that mTOR and HDAC inhibitors kill aggressive nervous system malignancies and shrink tumors in vivo by converging on the TXNIP/thioredoxin antioxidant pathway, through cooperative effects on chromatin and transcription. Accordingly, TXNIP triggers cell death by inhibiting thioredoxin and activating apoptosis signal-regulating kinase 1 (ASK1). Moreover, this drug combination also kills NF1-mutant and KRAS-mutant non–small cell lung cancers. Together, these studies identify a promising therapeutic combination for several currently untreatable malignancies and reveal a protective nodal point of convergence between these important epigenetic and oncogenic enzymes.

Significance: There are no effective therapies for NF1- or RAS-mutant cancers. We show that combined mTOR/HDAC inhibitors kill these RAS-driven tumors by causing catastrophic oxidative stress. This study identifies a promising therapeutic combination and demonstrates that selective enhancement of oxidative stress may be more broadly exploited for developing cancer therapies. Cancer Discov; 7(12); 1450–63. ©2017 AACR.

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Somatic Superenhancer Duplications and Hotspot Mutations Lead to Oncogenic Activation of the KLF5 Transcription Factor
Authors: Zhang Xiaoyang , Choi Peter S. , Francis Joshua M. , Gao Galen F. , Campbell Joshua D. , Ramachandran Aruna , Mitsuishi Yoichiro , Ha Gavin , Shih Juliann , Vazquez Francisca , Tsherniak Aviad , Taylor Alison M. , Zhou Jin , Wu Zhong , Berger Ashton C. , Giannakis Marios , Hahn William C. , Cherniack Andrew D. , Meyerson Matthew
Published: September 2017

The Krüppel-like family of transcription factors plays critical roles in human development and is associated with cancer pathogenesis. Krüppel-like factor 5 gene (KLF5) has been shown to promote cancer cell proliferation and tumorigenesis and to be genomically amplified in cancer cells. We recently reported that the KLF5 gene is also subject to other types of somatic coding and noncoding genomic alterations in diverse cancer types. Here, we show that these alterations activate KLF5 by three distinct mechanisms: (i) Focal amplification of superenhancers activates KLF5 expression in squamous cell carcinomas; (ii) Missense mutations disrupt KLF5–FBXW7 interactions to increase KLF5 protein stability in colorectal cancer; (iii) Cancer type–specific hotspot mutations within a zinc-finger DNA binding domain of KLF5 change its DNA binding specificity and reshape cellular transcription. Utilizing data from CRISPR/Cas9 gene knockout screening, we reveal that cancer cells with KLF5 overexpression are dependent on KLF5 for their proliferation, suggesting KLF5 as a putative therapeutic target.

Significance: Our observations, together with previous studies that identified oncogenic properties of KLF5, establish the importance of KLF5 activation in human cancers, delineate the varied genomic mechanisms underlying this occurrence, and nominate KLF5 as a putative target for therapeutic intervention in cancer. Cancer Discov; 8(1); 108–25. ©2017 AACR.

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