Process, structural, and outcome quality indicators to support perioperative opioid stewardship: a rapid review.

Opioids are effective analgesics but can cause harm. Opioid stewardship is key to ensuring that opioids are used effectively and safely. There is no agreed set of quality indicators relating to the use of opioids perioperatively. This work is part of the Yorkshire Cancer Research Bowel Cancer Quality Improvement programme and aims to develop useful quality indicators for the improvement of care and patient outcomes at all stages of the perioperative journey.A rapid review was performed to identify original research and reviews in which quality indicators for perioperative opioid use are described. A data tool was developed to enable reliable and reproducible extraction of opioid quality indicators.A review of 628 abstracts and 118 full-text publications was undertaken. Opioid quality indicators were identified from 47 full-text publications. In total, 128 structure, process and outcome quality indicators were extracted. Duplicates were merged, with the final extraction of 24 discrete indicators. These indicators are based on five topics: patient education, clinician education, pre-operative optimization, procedure, and patient-specific prescribing and de-prescribing and opioid-related adverse drug events.The quality indicators are presented as a toolkit to contribute to practical opioid stewardship. Process indicators were most commonly identified and contribute most to quality improvement. Fewer quality indicators relating to intraoperative and immediate recovery stages of the patient journey were identified. An expert clinician panel will be convened to agree which of the quality indicators identified will be most valuable in our region for the management of patients undergoing surgery for bowel cancer.

Prospective observational cohort study of the association between antiplatelet therapy, bleeding and thrombosis in patients with coronary stents undergoing noncardiac surgery.

BACKGROUND: The perioperative management of antiplatelet therapy in noncardiac surgery patients who have undergone previous percutaneous coronary intervention (PCI) remains a dilemma. Continuing dual antiplatelet therapy (DAPT) may carry a risk of bleeding, while stopping antiplatelet therapy may increase the risk of perioperative major adverse cardiovascular events (MACE). METHODS: Occurrence of Bleeding and Thrombosis during Antiplatelet Therapy In Non-Cardiac Surgery (OBTAIN) was an international prospective multicentre cohort study of perioperative antiplatelet treatment, MACE, and serious bleeding in noncardiac surgery. The incidences of MACE and bleeding were compared in patients receiving DAPT, monotherapy, and no antiplatelet therapy before surgery. Unadjusted risk ratios were calculated taking monotherapy as the baseline. The adjusted risks of bleeding and MACE were compared in patients receiving monotherapy and DAPT using propensity score matching. RESULTS: A total of 917 patients were recruited and 847 were eligible for inclusion. Ninety-six patients received no antiplatelet therapy, 526 received monotherapy with aspirin, and 225 received DAPT. Thirty-two patients suffered MACE and 22 had bleeding. The unadjusted risk ratio for MACE in patients receiving DAPT compared with monotherapy was 1.9 (0.93-3.88), P=0.08. There was no difference in MACE between no antiplatelet treatment and monotherapy 1.03 (0.31-3.46), P=0.96. Bleeding was more frequent with DAPT 6.55 (2.3-17.96) P=0.0002. In a propensity matched analysis of 177 patients who received DAPT and 177 monotherapy patients, the risk ratio for MACE with DAPT was 1.83 (0.69-4.85), P=0.32. The risk of bleeding was significantly greater in the DAPT group 4.00 (1.15-13.93), P=0.031. CONCLUSIONS: OBTAIN showed an increased risk of bleeding with DAPT and found no evidence for protective effects of DAPT from perioperative MACE in patients who have undergone previous PCI.

Abdominal aortic aneurysm repair in the United Kingdom: an exemplar for the role of anaesthetists in perioperative medicine.

The past two decades have seen an increasing recognition that the delivery of safe surgery with low complication rates and good long-term outcomes is a team endeavour embracing the whole patient care pathway. The key role of the anaesthetist in managing the patient through the surgical process is widely understood and has driven the emergence of perioperative medicine. In parallel with these developments there has been a sea change in the organisation of the care of patients presenting for elective abdominal aortic aneurysm (AAA) repair. Data from the 2008 report of the VASCUNET vascular registry suggested that the UK had the highest mortality for elective open AAA repair in Europe (7.9%). In response, a national quality improvement programme (AAAQIP) spanning the disciplines of surgery, anaesthesia, radiology and nursing was put in place. This led to significant changes in all aspects of AAA repair including the role of the anaesthetist. Preoperative assessment by an anaesthetist with a vascular practice was mandated and the role of the anaesthetist in the vascular multidisciplinary team meeting (MDT) established. Anaesthetic data were included in the national data collection system for vascular surgery, the National Vascular Registry. These changes paralleled and in some cases led the wider evolution of the role of the anaesthetist in perioperative medicine. The mortality from infrarenal AAA repair in the UK decreased to 2.4% by 2012. This improvement reflects changes in perioperative care supported and in some cases led by anaesthetists.

Panic symptoms in transient loss of consciousness: Frequency and diagnostic value in psychogenic nonepileptic seizures, epilepsy and syncope.

PURPOSE: Previous studies suggest that ictal panic symptoms are common in patients with psychogenic nonepileptic seizures (PNES). This study investigates the frequency of panic symptoms in PNES and if panic symptoms, just before or during episodes, can help distinguish PNES from the other common causes of transient loss of consciousness (TLOC), syncope and epilepsy. METHODS: Patients with secure diagnoses of PNES (n=98), epilepsy (n=95) and syncope (n=100) were identified using clinical databases from three United Kingdom hospitals. Patients self-reported the frequency with which they experienced seven symptoms of panic disorder in association with their episodes. A composite panic symptom score was calculated on the basis of the frequency of symptoms. RESULTS: 8.2% of patients with PNES reported "never" experiencing any of the seven panic symptoms in their episodes of TLOC. Patients with PNES reported more frequent panic symptoms in their attacks than those with epilepsy (p<0.001) or syncope (p<0.001), however, patients with PNES were more likely "rarely" or "never" to report five of the seven-ictal panic symptoms than "frequently" or "always" (45-69% versus 13-29%). A receiver operating characteristic analysis demonstrated that the composite panic symptom score distinguished patients with PNES from the other groups (sensitivity 71.1%, specificity 71.2%), but not epilepsy from syncope. CONCLUSIONS: Patients with PNES report TLOC associated panic symptoms more commonly than those with epilepsy or syncope. Although panic symptoms are reported infrequently by most patients with PNES, a composite symptom score may contribute to the differentiation between PNES and the other two common causes of TLOC.

Risk algorithms that include pathology adjustment for HER2 amplification need to make further downward adjustments in likelihood scores.

To assess the need for adjustment in the likelihood of germline BRCA1/2 mutations in women with HER2+ breast cancers. We analysed primary mutation screens on women with breast cancer with unequivocal HER2 overexpression and assessed the likelihood of BRCA1/BRCA2 mutations by age, oestrogen receptor status and Manchester score. Of 1111 primary BRCA screens with confirmed HER2 status only 4/161 (2.5%) of women with HER2 amplification had a BRCA1 mutation identified and 5/161 (3.1%) a BRCA2 mutation. The pathology adjusted Manchester score between 10 and 19% and 20%+ thresholds resulted in a detection rate of only 6.5 and 15% respectively. BOADICEA examples appeared to make even less downward adjustment. There is a very low detection rate of BRCA1 and BRCA2 mutations in women with HER2 amplified breast cancers. The Manchester score and BOADICEA do not make sufficient downward adjustment for HER2 amplification. For unaffected women, assessment of breast cancer risk and BRCA1/2 probability should take into account the pathology of the most relevant close relative. Unaffected women undergoing mutation testing for BRCA1/2 should be advised that there is limited reassurance from a negative test result if their close relative had a HER2+ breast cancer.

PO-31 - Circulating tumour cells and hypercoagulability: a lethal relationship in metastatic breast cancer.

INTRODUCTION: Circulating tumour cells (CTCs) are a marker of poor prognosis and are associated with increased risk of venous thromboembolism in metastatic breast cancer. AIM: We aimed to correlate presence of CTCs and markers of hyper-coagulability (D-dimer, fibrinogen and thrombin-antithrombin [TAT]) with survival in metastatic breast cancer. MATERIALS AND METHODS: In a prospective study, enumeration of CTCs (CellSearch) and D-dimer, fibrinogen and TAT (ELISA) were measured at a single timepoint in 50 MBC (median age 59, range 36-82) patients undergoing active treatment. Survival data was determined at a median follow-up of 366days (range 58-986). RESULTS: To date, 25 patients have died (median survival 566days, range 135-978). CTCs (>1/7.5ml) were identified in 13 patients (range 2-31) and were associated with increased markers of hypercoagulability [D-dimer: median 1814 (IQR 2700) vs 755 (IQR 735) ng/ml, p=0.004; fibrinogen: median 4.2 (IQR 1.9) vs 3.2 (1.3) g/l, p=0.05; TAT: median 6.2(IQR 6.3) vs 4.7 (5.2) ng/ml, p=0.1]. CTCs were associated with visceral compared to just bony metastases (p=0.03) and their presence was associated with a trend for reduced survival (295days (CI: 0-652) vs 737days (CI: 186-1288), p=0.1). There was no correlation between CTCs /markers of hypercoagulability and age, oestrogen receptor, progesterone receptor or Her2 status. D-dimer, fibrinogen and TAT all inversely correlated with survival and were all significantly higher in patients dying within 1year (D-dimer: 1098 (IQR 1122) vs 723 (IQR 735) ng/ml, p=0.03; fibrinogen: 4.4 (1.1) vs 3.2 (0.8) g/l, p=0.004; TAT: 8.1 (6.3) vs 4.7(3.1) ng/ml, p=0.03 [analysis excludes patients with <1year follow-up, n=13]). D-dimer >1,500ng/ml was associated with significantly reduced survival (295days [CI: 0-615] vs 836days [404-1267], p=0.05). On Cox regression, D-dimer, but not fibrinogen or TAT was associated with an increased risk of death (HR 1.3 per 1,000ng/ml D-dimer, p=0.07). CONCLUSIONS: The correlation between CTCs, hypercoagulability and reduced survival in metastatic breast cancer suggests a possible role for the coagulation system in supporting tumour cell metastasis and is therefore a potential therapeutic target.

A phase II trial of low-dose estradiol in postmenopausal women with advanced breast cancer and acquired resistance to aromatase inhibition.

BACKGROUND: High-dose oestrogen (HDE) is effective but toxic in postmenopausal women with advanced breast cancer (ABC). Prolonged oestrogen deprivation sensitises BC cell lines to estrogen and we hypothesised that third-generation aromatase inhibitors (AIs) would sensitise BCs to low-dose estradiol (LDE). METHODS: A single-arm phase II study of LDE (2 mg estradiol valerate daily) in postmenopausal women with estrogen receptor-positive (ER+) ABC. The primary end-point was clinical benefit (CB) rate. If LDE was ineffective, HDE was offered. If LDE was effective, retreatment with the pre-LDE AI was offered on progression. RESULTS: Twenty-one patients were recruited before the trial was closed early due to slow accrual; 19 were assessable for efficacy and toxicity. CB was seen in 5 in 19 patients (26%; 95% confidence interval 9.1-51.2%), all with prolonged SD (median duration 16.8 months; range 11.0-29.6). Treatment was discontinued for toxicity in 4 in 19 patients (21%) and 8 in 11 women without hysterectomy experienced vaginal bleeding (VB). After primary LDE failure, three patients received HDE and one achieved a partial response (PR). Following CB on LDE, four patients restarted pre-LDE AI and three achieved CB including one PR. Those with CB to LDE had a significantly longer duration of first-line endocrine therapy for ABC than those without (54.9 versus 16.8 months; p < 0.01) CONCLUSION: LDE is an effective endocrine option in women with evidence of prolonged sensitivity to AI therapy. LDE is reasonably well tolerated although VB is an issue. Re-challenge with the pre-LDE AI following progression confirms re-sensitisation as a true phenomenon.

Effect of supervised aerobic exercise rehabilitation on physical fitness and quality-of-life in survivors of critical illness: an exploratory minimized controlled trial (PIX study).

BACKGROUND: Evidence is limited for the effectiveness of interventions for survivors of critical illness after hospital discharge. We explored the effect of an 8-week hospital-based exercise-training programme on physical fitness and quality-of-life. METHODS: In a parallel-group minimized controlled trial, patients were recruited before hospital discharge or in the intensive care follow-up clinic and enrolled 8-16 weeks after discharge. Each week, the intervention comprised two sessions of physiotherapist-led cycle ergometer exercise (30 min, moderate intensity) plus one equivalent unsupervised exercise session. The control group received usual care. The primary outcomes were the anaerobic threshold (in ml O2 kg(-1) min(-1)) and physical function and mental health (SF-36 questionnaire v.2), measured at Weeks 9 (primary time point) and 26. Outcome assessors were blinded to group assignment. RESULTS: Thirty patients were allocated to the control and 29 to the intervention. For the anaerobic threshold outcome at Week 9, data were available for 17 control vs 13 intervention participants. There was a small benefit (vs control) for the anaerobic threshold of 1.8 (95% confidence interval, 0.4-3.2) ml O2 kg(-1) min(-1). This advantage was not sustained at Week 26. There was evidence for a possible beneficial effect of the intervention on self-reported physical function at Week 9 (3.4; -1.4 to 8.2 units) and on mental health at Week 26 (4.4; -2.4 to 11.2 units). These potential benefits should be examined robustly in any subsequent definitive trial. CONCLUSIONS: The intervention appeared to accelerate the natural recovery process and seems feasible, but the fitness benefit was only short term. CLINICAL TRIAL REGISTRATION: Current Controlled Trials ISRCTN65176374 (http://www.controlled-trials.com/ISRCTN65176374).

Meta-analysis of prospective trials determining the short- and mid-term effect of elective open and endovascular repair of abdominal aortic aneurysms on quality of life.

BACKGROUND: Repair of an abdominal aortic aneurysm (AAA) is undertaken to prevent rupture. Intervention is by either open repair (OR) or a more minimally invasive endovascular repair (EVAR). Quality-of-life (QoL) analysis is an important health outcome and a number of single studies have assessed QoL following OR and EVAR. This was a meta-analysis of published studies to assess the effect of an intervention on QoL in patients with an AAA. METHODS: A systematic literature search was undertaken for studies prospectively reporting QoL analysis in patients with an AAA undergoing elective intervention. A multivariable meta-analysis model was developed in which the outcomes were mean changes in QoL scores over time, both for all AAA repairs (OR and EVAR) and comparing OR with EVAR. RESULTS: Data were collated from 16 studies (14 OR, 12 EVAR). The results suggested that treating an AAA had an effect on patient-reported QoL, evident from the statistically significant changes predominantly in domains assessing physical ability and pain. QoL was affected most within the first 3 months after any form of intervention, and was more pronounced following OR. Furthermore, a deterioration in the Physical Component Summary score following an AAA repair (either OR or EVAR) was evident at 12 months after intervention. CONCLUSION: Treating an AAA deleteriously affects patient-reported QoL over the first year following intervention.

Diagnosing postoperative neuropathic pain: a Delphi survey.

BACKGROUND: Although postoperative pain is traditionally considered to be nociceptive in origin, a proportion of patients experience a significant neuropathic component to their pain experience. Diagnosing neuropathic pain in this setting is challenging, and there are no published guidelines or screening tools designed for use in the immediate postoperative setting. We hypothesized that acute pain specialists were diagnosing a neuropathic component to acute pain, and this study aimed to obtain an expert agreed list of pain characteristics that could be used to aid diagnosis. METHODS: A three-round Internet-based Delphi survey of acute pain specialists was used to generate a list of acute neuropathic pain characteristics, and achieve consensus on the importance of each item. Items were ranked on a 1-10 scale of importance, with a median score of ≥ 7 considered important and an inter-quartile range of ≤ 3 indicative of consensus. Cronbach's α was used to investigate internal consistency. RESULTS: Twenty-four items were generated by round 1 of the Delphi survey. Fourteen panellists participated in round 2, and 10 in round 3. After round 3, consensus of opinion was achieved for 13 items, with nine rated as important in the diagnosis of acute neuropathic pain. CONCLUSIONS: The Delphi survey suggests that neuropathic pain in the immediate postoperative period is diagnosed in a different way to chronic neuropathic pain, with items such as response to medications considered more useful than signs such as those representing autonomic changes.

National Institute of Academic Anaesthesia research priority setting exercise.

BACKGROUND: Formal research priority setting is a recognized way of identifying important clinical research questions and promoting these as topics for commissioned research. This paper describes a research priority setting exercise conducted by the National Institute of Academic Anaesthesia (NIAA). METHODS: Possible research questions were identified from a questionnaire sent to holders of the Final Fellowship in Anaesthesia in Great Britain and Ireland and to lay representatives. The responses to the first questionnaire were collated to produce a list of potential research questions which were then sent to the same constituency for scoring. The results of this scoring process were considered by an expert panel and statements of research need generated for selected questions. The questions from the first round were also reviewed with the help of representatives of NIHR Evaluation, Trials and Studies Coordinating Centre (NETSCC). RESULTS: For the first questionnaire, 308 responses with 447 suggestions for research were received. A total of 15 questions were included in the second questionnaire, for which 2226 responses were received. The expert panel identified five questions for prioritization. A further nine were identified from discussions with representatives of NETSCC. CONCLUSIONS: A total of 14 research priorities were identified by the exercise, two of which have been submitted to the NIHR Health Technology Assessment (HTA) programme as statements of research need. Potential funding streams for the remaining questions are being sought. We discuss some implications of this exercise for research strategy in the speciality.