Aintree – Effect of Fluticasone Furoate and Vilanterol on Exacerbations of Chronic Obstructive Pulmonary Disease in Patients with Moderate Airflow Obstruction.

Am J Respir Crit Care Med. 2017 Apr 1;195(7):881-888. doi: 10.1164/rccm.201607-1421OC

Martinez FJ1,2, Vestbo J3, Anderson JA4, Brook RD2, Celli BR5, Cowans NJ6, Crim C7, Dransfield M8, Kilbride S4, Yates J7, Newby DE9, Niewoehner D10, Calverley PM11; SUMMIT Investigators.

Author information:

1 Division of Pulmonary and Critical Care Medicine, Weill Cornell Medicine, New York, New York.

2 University of Michigan Health System, Ann Arbor, Michigan.

3 Division of Infection, Immunity and Respiratory Medicine, Manchester Academic Health Sciences Centre, The University of Manchester and South Manchester, Manchester, United Kingdom.

4 Research & Development, GlaxoSmithKline, Stockley Park, Middlesex, United Kingdom.

5 Pulmonary and Critical Care Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts.

6 Veramed Ltd., Twickenham, United Kingdom.

7 Research & Development, GlaxoSmithKline, Research Triangle Park, North Carolina.

8 University of Alabama Birmingham, Birmingham, Alabama.

9 Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.

10 University of Minnesota, Minneapolis, Minnesota; and.

11 University of Liverpool, Department of Medicine, Clinical Sciences Centre, University Hospital Aintree, Liverpool, United Kingdom.

Abstract

RATIONALE:

Inhaled corticosteroids have been shown to decrease exacerbations in patients with moderate to severe chronic obstructive pulmonary disease (COPD). Their effects in patients with milder airflow obstruction remain unclear.

OBJECTIVES:

This was an analysis of exacerbations in the SUMMIT (Study to Understand Mortality and Morbidity) study.

METHODS:

In a double-blind, randomized controlled trial, once-daily inhaled placebo, fluticasone furoate (FF; 100 μg), vilanterol (VI; 25 μg), or the combination of FF/VI was administered. The primary outcome was all-cause mortality. Exacerbations of COPD were an additional predefined endpoint. A total of 1,368 centers in 43 countries and 16,485 patients with moderate COPD and heightened cardiovascular risk were included in the study.

MEASUREMENTS AND MAIN RESULTS:

Compared with placebo, FF/VI reduced the rate of moderate and/or severe exacerbations by 29% (95% confidence interval [CI], 22-35; P < 0.001) and the rate of hospitalized exacerbations by 27% (95% CI, 13-39; P < 0.001). These relative effects were similar regardless of whether subjects had a history of exacerbation in the year before the study or an FEV1 <60% or ≥60% of predicted. The number needed to treat was not influenced by baseline FEV1 but was influenced by the history of exacerbations. FF/VI also reduced the rate of exacerbations treated with corticosteroids alone or with corticosteroids and antibiotics but not the rates of those treated with antibiotics alone.

CONCLUSIONS:

Patients with moderate chronic airflow obstruction experienced a reduction in exacerbations with FF/VI compared with placebo, irrespective of a history of exacerbations or baseline FEV1. Clinical trial registered with www.clinicaltrials.gov (NCT 01313676; GSK Study number 113782).

PMID: 27767328

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Aintree – Minimally Invasive Surgery for Pott’s Puffy Tumor: Is It Time for a Paradigm Shift in Managing a 250-Year-Old Problem?

Ann Otol Rhinol Laryngol. 2017 Jun;126(6):433-437. doi: 10.1177/0003489417698497. Epub 2017 Apr 4.

Leong SC1.

Author information:

1 Skull Base Unit, Department of Otorhinolaryngology – Head and Neck Surgery, Aintree University Hospital NHS Foundation Trust, Liverpool, UK.

Abstract

INTRODUCTION:

The aim of this study was to review the clinical outcomes and efficacy of endoscopic sinus surgery (ESS) in the management of Pott’s puffy tumor (PPT).

METHODS:

Literature PubMed review using a combination of MeSH terms and keywords was undertaken, combined with a single surgeon case series of 3 patients.

RESULTS:

A total of 29 (20 males, median age 25 years) cases were reviewed. The most common etiology was acute frontal sinusitis (62%), followed by a history of chronic rhinosinusitis (28%). Two patients presented with concomitant preseptal cellulitis and cutaneous fistula each, while another had pneumocephalus. The majority of cases (59%) had Draf 1 procedure. Three cases had Draf 3 procedure. Five cases were successfully treated by sinus balloon sinuplasty. Postoperatively, most patients had either oral or intravenous antibiotics of varying duration. There were no further complications following ESS. Both fistulas healed without requiring surgical debridement or closure.

CONCLUSION:

Some PPT cases can be managed endoscopically. The availability of powered angled instruments, high-definition video, and image guidance systems have provided the modern otolaryngologists with a credible alternative to traditional techniques. Furthermore, improved bioavailability of modern antibiotics may obviate the need for craniotomy and external drains.

PMID: 28376662

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Aintree – Cardiovascular outcomes with an inhaled beta2-agonist/corticosteroid in patients with COPD at high cardiovascular risk.

Heart. 2017 Apr 17. pii: heartjnl-2016-310897. doi: 10.1136/heartjnl-2016-310897. [Epub ahead of print]

Brook RD1, Anderson JA2, Calverley PM3,4, Celli BR5, Crim C6, Denvir MA7, Magder S8, Martinez FJ9, Rajagopalan S10, Vestbo J11, Yates J6, Newby DE12; SUMMIT Investigators.

Author information:

1 Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, USA robdbrok@umich.edu.

2 Research & Development, GlaxoSmithKline, Uxbridge, UK.

3 Department of Medicine, University of Liverpool, Liverpool, UK.

4 Clinical Sciences Centre, University Hospital Aintree, Liverpool, UK.

5 Pulmonary and Critical Care Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA.

6 Research & Development, GSK, Research Triangle Park, North Carolina, USA.

7 Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.

8 Research Institute of the McGill University Health Centre, McGill University, Montreal, Canada.

9 Joan and Sandy Weill Department of Medicine, Weill Cornell Medicine, New York, New York, USA.

10 Cardiovascular Medicine, University of Maryland, College Park, Maryland, USA.

11 Centre for Respiratory Medicine and Allergy, Manchester Academic Health Science Centre, The University of Manchester and South Manchester University Hospital NHS Foundation Trust, Manchester, UK.

12 British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.

Abstract

OBJECTIVES:

Cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) often coexist. We assessed the effect of inhaled COPD treatments on CVD outcomes and safety in patients with COPD and at heightened CVD risk.

METHODS:

The SUMMIT (Study to Understand Mortality and MorbidITy) was a multicentre, randomised, double-blind, placebo-controlled, event-driven trial in 16 485 patients with moderate COPD who had or were at high risk of CVD. Here, we assessed the prespecified secondary endpoint of time to first on-treatment composite CVD event (CVD death, myocardial infarction, stroke, unstable angina or transient ischaemic attack (TIA)) by Cox regression and by clinician-reported CVD adverse events across the four groups: once-daily inhaled placebo (n=4111), long-acting beta2-agonist (vilanterol (VI) 25 µg; n=4118), corticosteroid (fluticasone furoate (FF) 100 µg; n=4135) and combination therapy (FF/VI; n=4121).

RESULTS:

Participants were predominantly middle-aged (mean 65 (SD 8) years) men (75%) with overt CVD (66%). The composite CVD endpoint occurred in 688 patients (first event: sudden death (35%), acute coronary syndrome (37%) and stroke or TIA (23%)), and was not reduced in any treatment group versus placebo: VI (HR 0.99, 95% CI 0.80 to 1.22), FF (HR 0.90, 95% CI 0.72 to 1.11) and their combination (HR 0.93, 95% CI 0.75 to 1.14). Outcomes were similar among all subgroups. Adverse events, including palpitations and arrhythmias, did not differ by treatment.

CONCLUSIONS:

In patients with COPD with moderate airflow limitation and heightened CVD risk, treatment with inhaled VI, FF or their combination has an excellent safety profile and does not impact CVD outcomes.

TRIAL REGISTRATION NUMBER:

NCT01313676.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Free Article

PMID: 28416587

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Aintree – Transoral orthodromic temporalis muscle transfer technique for the paralysed midface: Our learning curve experience from the first 10 cases.

Clin Otolaryngol. 2017 Apr 21. doi: 10.1111/coa.12888. [Epub ahead of print]

Lazarova L1, Lesser TH1,2, Leong SC1,2.

Author information:

1 Facial Palsy Service, Department of Otorhinolaryngology – Head and Neck Surgery, Aintree University Hospital, Liverpool.

2 Skull Base Unit, Department of Otorhinolaryngology – Head and Neck Surgery, Aintree University Hospital, Liverpool.

Abstract

Sir Harold Gillies first described rotating a band of temporalis muscle over the zygoma where the muscle sling was augmented with strips of fascia lata to rehabilitate facial paralysis 1 . McLaughlin later modified this technique in the 1950s without inversion of the temporal muscle but in an orthodromic manner thus avoiding the soft tissue fullness over the zygomatic arch area and depression of the donor site 2 . Although several refinements of this technique have been described, all required skin incisions on the face until a transoral technique was described recently by this clinical group 3 . This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

PMID: 28429472

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Aintree – Ambulatory thyroidectomy: an anesthesiologist’s perspective.

Local Reg Anesth. 2017 Apr 5;10:31-39. doi: 10.2147/LRA.S111554. eCollection 2017.

Murray B1, Tandon S2, Dempsey G1.

Author information:

1 Department of Anaesthesia and Critical Care.

2 Department of Otolaryngology, Head & Neck Surgery, Aintree University Hospital NHS Foundation Trust, Liverpool, UK.

Abstract

Thyroidectomy has been performed on an inpatient basis because of concerns regarding postoperative complications. These include cervical hematoma, bilateral recurrent laryngeal nerve injury and symptomatic hypocalcemia. We have reviewed the current available evidence and aimed to collate published data to generate incidence of the important complications. We performed a literature search of Medline, EMBASE and the Cochrane database of randomized trials. One hundred sixty papers were included. Twenty-one papers fulfilled inclusion criteria. Thirty thousand four hundred fifty-three day-case thyroid procedures were included. Ten papers were prospective and 11 retrospective. The incidences of complications were permanent vocal cord paralysis 7/30259 (0.02%), temporary hypocalcemia 129/4444 (2.9%), permanent hypocalcemia 405/29203 (1.39%), cervical hematoma 145/30288 (0.48%) and readmission rate 105/29609 (0.35%). Analysis of cervical hematoma data demonstrated that in only 3/14 cases the hematoma presented as an inpatient, and in the remaining 11/14, it occurred late, with a range of 2-9 days. There is a paucity of data relating to anesthetic techniques associated with ambulatory thyroidectomy. Cost comparison between outpatient and inpatient thyroidectomy was reported in three papers. Cost difference ranged from $676 to $2474 with a mean saving of $1301 with ambulatory thyroidectomy. There is a body of evidence that suggests that ambulatory thyroidectomy in the hands of experienced operating teams within an appropriate setting can be performed with acceptable risk profile. In most circumstances, this will be limited to hemithyroidectomies to reduce or avoid the potential for additional morbidity. We have found little evidence to support the use of one anesthetic technique over another. The rates of hospital admission and readmission related to anesthetic factors appear to be low and predominantly related to pain and postoperative nausea and vomiting. A balanced anesthetic technique incorporating appropriate analgesic and antiemetic regimens is essential to avoid unnecessary hospital admission/readmission.

PMCID: PMC5388280 Free PMC Article

PMID: 28435323

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Aintree – Characterisation of drug-specific signalling between primary human hepatocytes and immune cells.

Toxicol Sci. 2017 Apr 21. doi: 10.1093/toxsci/kfx069. [Epub ahead of print]

Ogese MO1, Faulkner L2, Jenkins RE2, French NS2, Copple IM2, Antoine DJ2, Elmasry M2,3, Malik H3, Goldring CE2, Kevin Park B2, Betts C1, Naisbitt DJ2.

Author information:

1 Pathology Sciences, Drug Safety and Metabolism, AstraZeneca R&D, Darwin Building 310, Cambridge Science Park, Milton Rd, Cambridge CB4 0WG, United Kingdom.

2 MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, University of Liverpool, Ashton Street, Liverpool L69 3GE, United Kingdom.

3 North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool L9 7AL, UK.

Abstract

It is now apparent that antigen-specific T-cells are activated in certain patients with drug-induced liver injury (DILI). Since cross-talk between hepatocytes and immune cells is likely to be critical in determining the outcome of drug exposure, the aim of this study was to profile the signals released by drug-treated hepatocytes and to characterise the impact of these molecules on dendritic cells. Human hepatocytes were exposed to three drugs (flucloxacillin, amoxicillin and isoniazid) associated with DILI potentially mediated by the adaptive immune system as drug-specific T-cells have been isolated from DILI patients, and the metabolite nitroso-sulfamethoxazole (SMX-NO). Hepatocyte toxicity, cytokine release and activation of oxidative stress pathways were measured. Supernatants were transferred to monocyte-derived dendritic cells and cell phenotype and function were assessed. High-mobility group box 1 protein (HMGB1) and lactate dehydrogenase release as well as adenosine triphosphate depletion occurred in a drug-, time- and concentration-dependent manner with SMX-NO and flucloxacillin, whereas isoniazid and amoxicillin were non-toxic. Furthermore, drug-induced activation of Nrf2 marker genes was observed when hepatocytes were exposed to test drugs. The disulphide isoform of HMGB1 stimulated dendritic cell cytokine release and enhanced the priming of naive T cells. Incubation of dendritic cells with supernatant from drug-treated hepatocytes resulted in two distinct cytokine profiles. SMX-NO/flucloxacillin stimulated secretion of TNF-á, IL-6, IL-1á and IL-1-â. Isoniazid which did not induce significant hepatocyte toxicity, compared with SMX-NO and flucloxacillin, stimulated the release of a panel of cytokines including the above and IFN-γ, IL-12, IL-17A, IP-10 and IL-10. Collectively, our study identifies drug-specific signalling pathways between hepatocytes and immune cells that could influence whether drug exposure will result in an immune response and tissue injury.

© The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

PMID: 28444390

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Aintree – Postoperative radiotherapy for patients with oral squamous cell carcinoma with intermediate risk of recurrence: A case match study.

Head Neck. 2017 Apr 28. doi: 10.1002/hed.24780. [Epub ahead of print]

Barry CP1,2,3,4, Wong D1, Clark JR2,5, Shaw RJ1,6, Gupta R3,7, Magennis P1, Triantafyllou A1, Gao K2, Brown JS1,6.

Author information:

1 Liverpool Head and Neck Cancer Unit, Aintree University Hospital, Liverpool, Merseyside, United Kingdom.

2 Sydney Head and Neck Cancer Institute, Chris O Brien Lifehouse, Sydney, New South Wales, Australia.

3 National Maxillofacial Unit, St. James’s Hospital, Dublin, Ireland.

4 Dublin Dental University Hospital, Dublin, Ireland.

5 Central Clinical School, University of Sydney, Sydney, New South Wales, Australia.

6 Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, Merseyside, United Kingdom.

7 Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, Australia.

Abstract

BACKGROUND:

The purpose of this study was to determine the effect of postoperative radiotherapy (PORT) on recurrence and survival in patients with oral squamous cell carcinoma (OSCC) of intermediate recurrence risk.

METHODS:

Intermediate risk patients, defined as pT1, pT2, pN0, or pN1 with at least one adverse pathological feature (eg, lymphovascular/perineural invasion), were identified from the head and neck databases of the Liverpool Head and Neck Cancer Unit and the Sydney Head and Neck Cancer Institute. Patients who received surgery and PORT were case matched with patients treated by surgery alone based on pN, pT, margins, and pathological features.

RESULTS:

Ninety patients were matched into 45 pairs. There was significant improvement (P = .039) in locoregional control with PORT (84%) compared with surgery alone (60%), which was concentrated in the pN1 subgroup (P = .036), but not the pN0 subgroup (P = .331).

CONCLUSION:

PORT significantly improves locoregional control for intermediate risk OSCC.

© 2017 Wiley Periodicals, Inc.

PMID: 28452199

Aintree – The implementation of the Vessel Health and Preservation framework.

Br J Nurs. 2017 Apr 27;26(8):S18-S22. doi: 10.12968/bjon.2017.26.8.S18.

Weston V1, Nightingale A2, O’Loughlin C3, Ventura R3.

Author information:

1 Lead Nurse Infection Prevention and Control and IPS IV Forum Co-ordinator, St Helens and Knowsley Teaching Hospitals NHS Trust, Whiston Hospital.

2 Senior Lecturer in Perioperative studies, Edge Hill University, St Helens Road, Ormskirk, Lancashire.

3 IV Access Specialist Nurse, Aintree University Hospital NHS Foundation Trust, Liverpool.

Abstract

Vascular access is an important component of health care but is not without associated risks, some of which can be life-threatening. The Vessel Health and Preservation (VHP) framework was developed with the intention of providing frontline staff with a resource to assist in assessing and selecting the best vascular access device to meet individual patient needs and to preserve veins for future use. This article examines the impact of the introduction of the framework into a haematology ward in an acute hospital in the North West of England during a 3-month pilot study. The results indicate that the VHP framework gave nursing staff more autonomy to choose the appropriate vascular access device for their patients and improved staff knowledge around pH and osmolality of intravenous drugs. However it is clear that more in-depth evaluations need to be conducted to assess the impact of VHP on patient care and outcomes.

PMID: 28453315

Aintree – Peripheral intravenous cannulation: protecting patients and nurses.

Br J Nurs. 2017 Apr 27;26(8):S28-S33. doi: 10.12968/bjon.2017.26.8.S28.

Barton A1, Ventura R2, Vavrik B3.

Author information:

1 Advanced Nurse Practitioner-Vascular Access & IV Therapy, Frimley Health NHS Foundation Trust.

2 IV Access Specialist Nurse, Aintree University NHS Foundation Trust.

3 Registered Nurse, Medical Student, Queen’s University Belfast.

Abstract

Peripheral intravenous cannulation is a common clinical procedure in today’s healthcare setting. There are a range of different devices to choose from, and this article will consider the risk of catheter-related bloodstream infections and needlestick injuries, national and international guidelines on infection prevention and safety in intravenous access, the need for closed catheters, features of the Introcan Safety® 3 (B. Braun Melsungen AG) and research into peripheral cannulas.

PMID: 28453316

Aintree – SOARD Journal Club – a Dedicated Forum for the Critical Analysis of SOARD Publications.

Surg Obes Relat Dis. 2017 Apr;13(4):545-546. doi: 10.1016/j.soard.2017.01.026. pub 2017 Jan 17.

Khwaja HA1, Peterson RM2.

Author information:

1 Phoenix Health Bariatric Surgery Supercenter, University Hospital Aintree, Liverpool, United Kingdom.

2 Department of General and Minimally Invasive Surgery, University of Texas Health Science Center San Antonio, San Antonio, Texas. Electronic address: petersonr3@uthscsa.edu.

PMID: 28483349