Regional anaesthesia practice for arteriovenous fistula formation surgery.

We conducted a survey and semi-structured qualitative interviews to investigate current anaesthetic practice for arteriovenous fistula formation surgery in the UK. Responses were received from 39 out of 59 vascular centres where arteriovenous access surgery is performed, a response rate of 66%. Thirty-five centres reported routine use of brachial plexus blocks, but variation in anaesthetic skill-mix and practice were observed. Interviews were conducted with 19 clinicians from 10 NHS Trusts including anaesthetists, vascular access and renal nurses, surgeons and nephrologists. Thematic analysis identified five key findings: (1) current anaesthetic practice showed that centres could be classified as 'regional anaesthesia dominant' or 'local anaesthesia/mixed'; (2) decision making around mode of anaesthesia highlighted the key role of surgeons as frontline decision makers across both centre types; (3) perceived barriers and facilitators of regional block use included clinicians' beliefs and preferences, resource considerations and patients' treatment preferences; (4) anaesthetists' preference for supraclavicular blocks emerged, alongside acknowledgement of varied practice; (5) there was widespread support for a future randomised controlled trial, although clinician equipoise issues and logistical/resource-related concerns were viewed as potential challenges. The use of regional anaesthesia for arteriovenous fistula formation in the UK is varied and influenced by a multitude of factors. Despite the availability of anaesthetists capable of performing regional blocks, there are other limiting factors that influence the routine use of this technique. The study also highlighted the perceived need for a large multicentre, randomised controlled trial to provide an evidence base to inform current practice.

Local anaesthesia for endovascular repair of ruptured abdominal aortic aneurysm.

BACKGROUND: Case series and a post hoc subgroup analysis of a large randomized trial have suggested a potential benefit in treating ruptured abdominal aortic aneurysms (rAAAs) using endovascular aneurysm repair (EVAR) with local anaesthesia (LA) rather than general anaesthesia (GA). The uptake and outcomes of LA in clinical practice remain unknown. METHODS: The UK National Vascular Registry was interrogated for patients presenting with rAAA managed with EVAR under different modes of anaesthesia between 1 January 2014 and 31 December 2016. The primary outcome was in-hospital mortality. Secondary outcomes included: the number of centres performing EVAR under LA; the proportion of patients receiving this technique; duration of hospital stay; and postoperative complications. RESULTS: Some 3101 patients with rAAA were treated in 72 hospitals during the study: 2306 underwent on open procedure and 795 had EVAR (LA, 319; GA, 435; regional anaesthesia, 41). Overall, 56 of 72 hospitals (78 per cent) offered LA for EVAR of rAAA. Baseline characteristics and morphology were similar across the three EVAR subgroups. Patients who had surgery under LA had a lower in-hospital mortality rate than patients who received GA (59 of 319 (18·5 per cent) versus 122 of 435 (28·0 per cent)), and this was unchanged after adjustment for factors known to influence survival (adjusted hazard ratio 0·62, 95 per cent c.i. 0·45 to 0·85; P = 0·003). Median hospital stay and postoperative morbidity from other complications were similar. CONCLUSION: The use of LA for EVAR of rAAA has been adopted widely in the UK. Mortality rates appear lower than in patients undergoing EVAR with GA.

Randomized trial of near-infrared spectroscopy for personalized optimization of cerebral tissue oxygenation during cardiac surgery.

BACKGROUND: We assessed whether a near-infrared spectroscopy (NIRS)-based algorithm for the personalized optimization of cerebral oxygenation during cardiopulmonary bypass combined with a restrictive red cell transfusion threshold would reduce perioperative injury to the brain, heart, and kidneys. METHODS: In a randomized controlled trial, participants in three UK centres were randomized with concealed allocation to a NIRS (INVOS 5100; Medtronic Inc., Minneapolis, MN, USA)-based 'patient-specific' algorithm that included a restrictive red cell transfusion threshold (haematocrit 18%) or to a 'generic' non-NIRS-based algorithm (standard care). The NIRS algorithm aimed to maintain cerebral oxygenation at an absolute value of > 50% or at > 70% of baseline values. The primary outcome for the trial was cognitive function measured up to 3 months postsurgery. RESULTS: The analysis population comprised eligible randomized patients who underwent valve or combined valve surgery and coronary artery bypass grafts using cardiopulmonary bypass between December 2009 and January 2014 ( n =98 patient-specific algorithm; n =106 generic algorithm). There was no difference between the groups for the three core cognitive domains (attention, verbal memory, and motor coordination) or for the non-core domains psychomotor speed and visuo-spatial skills. The NIRS group had higher scores for verbal fluency; mean difference 3.73 (95% confidence interval 1.50, 5.96). Red cell transfusions, biomarkers of brain, kidney, and myocardial injury, adverse events, and health-care costs were similar between the groups. CONCLUSIONS: These results do not support the use of NIRS-based algorithms for the personalized optimization of cerebral oxygenation in adult cardiac surgery. CLINICAL TRIAL REGISTRATION: http://www.controlled-trials.com , ISRCTN 23557269.

Enabling recruitment success in bariatric surgical trials: pilot phase of the By-Band-Sleeve study.

BACKGROUND: Randomized controlled trials (RCTs) involving surgical procedures are challenging for recruitment and infrequent in the specialty of bariatrics. The pilot phase of the By-Band-Sleeve study (gastric bypass versus gastric band versus sleeve gastrectomy) provided the opportunity for an investigation of recruitment using a qualitative research integrated in trials (QuinteT) recruitment intervention (QRI). PATIENTS/METHODS: The QRI investigated recruitment in two centers in the pilot phase comparing bypass and banding, through the analysis of 12 in-depth staff interviews, 84 audio recordings of patient consultations, 19 non-participant observations of consultations and patient screening data. QRI findings were developed into a plan of action and fed back to centers to improve information provision and recruitment organization. RESULTS: Recruitment proved to be extremely difficult with only two patients recruited during the first 2 months. The pivotal issue in Center A was that an effective and established clinical service could not easily adapt to the needs of the RCT. There was little scope to present RCT details or ensure efficient eligibility assessment, and recruiters struggled to convey equipoise. Following presentation of QRI findings, recruitment in Center A increased from 9% in the first 2 months (2/22) to 40% (26/65) in the 4 months thereafter. Center B, commencing recruitment 3 months after Center A, learnt from the emerging issues in Center A and set up a special clinic for trial recruitment. The trial successfully completed pilot recruitment and progressed to the main phase across 11 centers. CONCLUSIONS: The QRI identified key issues that enabled the integration of the trial into the clinical setting. This contributed to successful recruitment in the By-Band-Sleeve trial-currently the largest in bariatric practice-and offers opportunities to optimize recruitment in other trials in bariatrics.

Adaptation of the By-Band randomized clinical trial to By-Band-Sleeve to include a new intervention and maintain relevance of the study to practice.

BACKGROUND: Recruitment into surgical RCTs can be threatened if new interventions available outside the trial compete with those being evaluated. Adapting the trial to include the new intervention may overcome this issue, yet this is not often done in surgery. This paper describes the challenges, rationale and methods for adapting an RCT to include a new intervention. METHODS: The By-Band study was designed in the UK in 2009-2010 to compare the effectiveness of laparoscopic adjustable gastric band and Roux-en-Y gastric bypass for severe obesity. It contained a pilot phase to establish whether recruitment was possible, and the grant proposal specified that an adaptation to include sleeve gastrectomy would be considered if practice changed and recruitment was successful. Information on changing obesity surgery practice, updated evidence and expert opinion about trial design were used to inform the adaptation. RESULTS: The pilot phase recruited over 13 months in 2013-2014 and randomized 80 patients (79 anticipated). During this time, major changes in obesity practice in the UK were observed, with gastric band reducing from 32·6 to 15·8 per cent and sleeve gastrectomy increasing from 9·0 to 28·1 per cent. The evidence base had not changed markedly. The British Obesity and Metabolic Surgery Society and study oversight committees supported an adaptation to include sleeve gastrectomy, and a proposal to do so was approved by the funder. CONCLUSION: Adaptation of a two-group surgical RCT can allow evaluation of a third procedure and maintain relevance of the RCT to practice. It also optimizes the use of existing trial infrastructure to answer an additional important research question. Registration number: ISRCTN00786323 (http://www.isrctn.com/).

Home-based Reach-to-Grasp training for people after stroke is feasible: a pilot randomised controlled trial.

OBJECTIVE: To determine feasibility of a randomised controlled trial (RCT) of home-based Reach-to-Grasp training after stroke. DESIGN: single-blind parallel group RCT. PARTICIPANTS: Residual arm deficit less than 12 months post-stroke. INTERVENTIONS: Reach-to-Grasp training in 14 one-hour therapist's visits over 6 weeks, plus one hour self-practice per day (total 56 hours). CONTROL: Usual care. MAIN MEASURES: Action Research Arm Test (ARAT), Wolf Motor Function Test (WMFT), pre-randomisation, 7, 12, 24 weeks post-randomisation. RESULTS: Forty-seven participants (Reach-to-Grasp=24, usual care=23) were randomised over 17 months. Reach-to-Grasp participants received a median (IQR) 14 (13,14) visits, and performed 157 (96,211) repetitions per visit; plus 30 minutes (22,45) self-practice per day. Usual care participants received 10.5 (5,14) therapist visits, comprising 38.6 (30,45) minutes of arm therapy with 16 (6,24) repetitions of functional tasks per visit. Median ARAT scores in the reach-to-grasp group were 8.5 (3.0,24.0) at baseline and 14.5 (3.5,26.0) at 24 weeks compared to median of 4 at both time points (IQR: baseline (3.0,14.0), 24 weeks (3.0,30.0)) in the usual-care group. Median WMFT tasks completed at baseline and 24 weeks were 6 (3.0,11.5) and 8.5 (4.5,13.5) respectively in the reach-to-grasp group and 4 (3.0,10.0), 6 (3.0,14.0) in the usual care group. Incidence of arm pain was similar between groups. The study was stopped before 11 patients reached the 24 weeks assessment. CONCLUSIONS: An RCT of home-based Reach-to-Grasp training after stroke is feasible and safe. With ARAT being our preferred measure it is estimated that 240 participants will be needed for a future two armed trial.

Cost-effectiveness of community versus hospital eye service follow-up for patients with quiescent treated age-related macular degeneration alongside the ECHoES randomised trial.

OBJECTIVES: To assess the cost-effectiveness of optometrist-led follow-up monitoring reviews for patients with quiescent neovascular age-related macular degeneration (nAMD) in community settings (including high street opticians) compared with ophthalmologist-led reviews in hospitals. DESIGN: A model-based cost-effectiveness analysis with a 4-week time horizon, based on a 'virtual' non-inferiority randomised trial designed to emulate a parallel group design. SETTING: A virtual internet-based clinical assessment, conducted at community optometry practices, and hospital ophthalmology clinics. PARTICIPANTS: Ophthalmologists with experience in the age-related macular degeneration service; fully qualified optometrists not participating in nAMD shared care schemes. INTERVENTIONS: The participating optometrists and ophthalmologists classified lesions from vignettes and were asked to judge whether any retreatment was required. Vignettes comprised clinical information, colour fundus photographs and optical coherence tomography images. Participants' classifications were validated against experts' classifications (reference standard). Resource use and cost information were attributed to these retreatment decisions. MAIN OUTCOME MEASURES: Correct classification of whether further treatment is needed, compared with a reference standard. RESULTS: The mean cost per assessment, including the subsequent care pathway, was £411 for optometrists and £397 for ophthalmologists: a cost difference of £13 (95% CI -£18 to £45). Optometrists were non-inferior to ophthalmologists with respect to the overall percentage of lesions correctly assessed (difference -1.0%; 95% CI -4.5% to 2.5%). CONCLUSIONS: In the base case analysis, the slightly larger number of incorrect retreatment decisions by optometrists led to marginally and non-significantly higher costs. Sensitivity analyses that reflected different practices across eye hospitals indicate that shared care pathways between optometrists and ophthalmologists can be identified which may reduce demands on scant hospital resources, although in light of the uncertainty around differences in outcome and cost it remains unclear whether the differences between the 2 care pathways are significant in economic terms. TRIAL REGISTRATION NUMBER: ISRCTN07479761; Pre-results.

Are lower levels of red blood cell transfusion more cost-effective than liberal levels after cardiac surgery? Findings from the TITRe2 randomised controlled trial.

OBJECTIVE: To assess the incremental cost and cost-effectiveness of a restrictive versus a liberal red blood cell transfusion threshold after cardiac surgery. DESIGN: A within-trial cost-effectiveness analysis with a 3-month time horizon, based on a multicentre superiority randomised controlled trial from the perspective of the National Health Service (NHS) and personal social services in the UK. SETTING: 17 specialist cardiac surgery centres in UK NHS hospitals. PARTICIPANTS: 2003 patients aged >16 years undergoing non-emergency cardiac surgery with a postoperative haemoglobin of <9 g/dL. INTERVENTIONS: Restrictive (transfuse if haemoglobin <7.5 g/dL) or liberal (transfuse if haemoglobin <9 g/dL) threshold during hospitalisation after surgery. MAIN OUTCOME MEASURES: Health-related quality of life measured using the EQ-5D-3L to calculate quality-adjusted life years (QALYs). RESULTS: The total costs from surgery up to 3 months were £17 945 and £18 127 in the restrictive and liberal groups (mean difference is -£182, 95% CI -£1108 to £744). The cost difference was largely attributable to the difference in the cost of red blood cells. Mean QALYs to 3 months were 0.18 in both groups (restrictive minus liberal difference is 0.0004, 95% CI -0.0037 to 0.0045). The point estimate for the base-case cost-effectiveness analysis suggested that the restrictive group was slightly more effective and slightly less costly than the liberal group and, therefore, cost-effective. However, there is great uncertainty around these results partly due to the negligible differences in QALYs gained. CONCLUSIONS: We conclude that there is no clear difference in the cost-effectiveness of restrictive and liberal thresholds for red blood cell transfusion after cardiac surgery. TRIAL REGISTRATION NUMBER: ISRCTN70923932; Results.

Standardizing and monitoring the delivery of surgical interventions in randomized clinical trials.

BACKGROUND: The complexity of surgical interventions has major implications for the design of RCTs. Trials need to consider how and whether to standardize interventions so that, if successful, they can be implemented in practice. Although guidance exists for standardizing non-pharmaceutical interventions in RCTs, their application to surgery is unclear. This study reports new methods for standardizing the delivery of surgical interventions in RCTs. METHODS: Descriptions of 160 surgical interventions in existing trial reports and protocols were identified. Initially, ten reports were scrutinized in detail using a modified framework approach for the analysis of qualitative data, which informed the development of a preliminary typology. The typology was amended with iterative sequential application to all interventions. Further testing was undertaken within ongoing multicentre RCTs. RESULTS: The typology has three parts. Initially, the overall technical purpose of the intervention is described (exploration, resection and/or reconstruction) in order to establish its constituent components and steps. This detailed description of the intervention is then used to establish whether and how each component and step should be standardized, and the standards documented within the trial protocol. Finally, the typology provides a framework for monitoring the agreed intervention standards during the RCT. Pilot testing within ongoing RCTs enabled standardization of the interventions to be agreed, and case report forms developed to capture deviations from these standards. CONCLUSION: The typology provides a framework for use during trial design to standardize the delivery of surgical interventions and document these details within protocols. Application of this typology to future RCTs may clarify details of the interventions under evaluation and help successful interventions to be implemented.

The design and implementation of a study to investigate the effectiveness of community vs hospital eye service follow-up for patients with neovascular age-related macular degeneration with quiescent disease.

IntroductionStandard treatment for neovascular age-related macular degeneration (nAMD) is intravitreal injections of anti-VEGF drugs. Following multiple injections, nAMD lesions often become quiescent but there is a high risk of reactivation, and regular review by hospital ophthalmologists is the norm. The present trial examines the feasibility of community optometrists making lesion reactivation decisions.MethodsThe Effectiveness of Community vs Hospital Eye Service (ECHoES) trial is a virtual trial; lesion reactivation decisions were made about vignettes that comprised clinical data, colour fundus photographs, and optical coherence tomograms displayed on a web-based platform. Participants were either hospital ophthalmologists or community optometrists. All participants were provided with webinar training on the disease, its management, and assessment of the retinal imaging outputs. In a balanced design, 96 participants each assessed 42 vignettes; a total of 288 vignettes were assessed seven times by each professional group.The primary outcome is a participant's judgement of lesion reactivation compared with a reference standard. Secondary outcomes are the frequency of sight threatening errors; judgements about specific lesion components; participant-rated confidence in their decisions about the primary outcome; cost effectiveness of follow-up by optometrists rather than ophthalmologists.DiscussionThis trial addresses an important question for the NHS, namely whether, with appropriate training, community optometrists can make retreatment decisions for patients with nAMD to the same standard as hospital ophthalmologists. The trial employed a novel approach as participation was entirely through a web-based application; the trial required very few resources compared with those that would have been needed for a conventional randomised controlled clinical trial.

Pollen counts and suicide rates. Association not replicated.

OBJECTIVE: To replicate a previously reported association between pollen counts and county suicide rates in the continental United States, across space and time. METHOD: The authors evaluated the relationship between airborne pollen counts and suicide rates in 42 counties of the continental United States, containing a pollen-counting station participating in the Aeroallergen Monitoring Network in the United States (N = 120,076 suicides), considering years' quarter, age group, sex, race, rural/urban location, number of local psychiatrists, and median household income, from 1999 to 2002. The county-level effects were broken into between-county and within-county. RESULTS: No within-county effects were found. Between-county effects for grass and ragweed pollen on suicide rates lost statistical significance after adjustment for median income, number of psychiatrists, and urban vs. rural location. CONCLUSION: Future research is necessary to reappraise the previously reported relationship between pollen levels and suicide rates that may have been driven by socioeconomic confounders.

Disease-specific survival benefit of lung transplantation in adults: a national cohort study.

The lung transplantation candidate population is heterogeneous and survival benefit has not been established for all patient groups. UK data from a cohort of 1997 adult (aged > or = 16), first lung transplant candidates (listed July 1995 to July 2006, follow-up to December 2007) were analyzed by diagnosis, to assess mortality relative to continued listing. Donor lungs were primarily allocated according to local criteria. Diagnosis groups studied were cystic fibrosis (430), bronchiectasis (123), pulmonary hypertension (74), diffuse parenchymal lung disease (564), chronic obstructive pulmonary disease (COPD, 647) and other (159). The proportion of patients in each group who died while listed varied significantly (respectively 37%, 48%, 41%, 49%, 19%, 38%). All groups had an increased risk of death at transplant, which fell below waiting list risk of death within 4.3 months. Thereafter, the hazard ratio for death relative to listing ranged from 0.34 for cystic fibrosis to 0.64 for COPD (p < 0.05 all groups except pulmonary hypertension). Mortality reduction was greater after bilateral lung transplantation in pulmonary fibrosis patients (p = 0.049), but not in COPD patients. Transplantation appeared to improve survival for all groups. Differential waiting list and posttransplant mortality by diagnosis suggest further use and development of algorithms to inform lung allocation.

Inadequate blood glucose control is associated with in-hospital mortality and morbidity in diabetic and nondiabetic patients undergoing cardiac surgery.

BACKGROUND: Derangement of glucose metabolism after surgery is not specific to patients with diabetes mellitus. We investigated the effect of different degrees of blood glucose control (BGC) on clinical outcomes after cardiac surgery. METHODS AND RESULTS: We analyzed 8727 adults operated on between April 1996 and March 2004. The highest blood glucose level recorded over the first 60 hours postoperatively was used to classify patients as having good (<200 mg/dL), moderate (200 to 250 mg/dL), or poor (>250 mg/dL) BGC; 7547 patients (85%) had good, 905 (10%) had moderate, and 365 (4%) had poor BGC. Patients with inadequate BGC were more likely to present with advanced New York Heart Association class, congestive heart failure, hypertension, renal dysfunction, and ejection fraction <50% (P0

Mechanical heart valves in septuagenarians.

AIM: To report on the use of a third-generation bileaflet mechanical valve in septuagenarians, selected to receive a mechanical valve, as compared to (a) a younger cohort undergoing same valve implant (study 1) and to (b) a matched group of septuagenarians undergoing biological implant (study 2). METHODS: The study was carried out in a tertiary regional hospital in South-West England. Study 1: Consecutive series of 567 patients undergoing Sorin Bileaflet (SB) mechanical valve implant (437 patients < 70 years; 130 patients >or= 70 years). Study 2: 113 septuagenarians undergoing biological implant matched on age, valve type, concomitant coronary surgery, and operative priority to the SB septuagenarian group. Main outcome measures included in-hospital mortality and morbidity and mid-term valve-related outcome. RESULTS: Study 1: Septuagenarians were more likely to present with coronary disease, and to undergo coronary surgery (p < 0.01). In-hospital mortality was 2.8% and 2.3% (p = 0.79) and neurological complications 1.4% versus 3.8% (p = 0.026) in the younger and older groups, respectively. Valve-related mortality at two years was 1.8% (95%CI, 0.8% to 3.6%) and 4.8% (95% CI, 2.0% to 9.7%); cumulative three- year incidence of thromboembolic or major hemorrhagic event was 8.3% (95% CI, 5.7% to 12.0%) and 4.6% (95% CI, 1.7% to 12.4%) in the younger and older groups, respectively. Study 2: In-hospital mortality was 1.8% and 7.1% in the SB and biological groups, respectively (ratio 0.25; 95% CI, 0.05 to 1.18, p = 0.058). The incidence of acute renal failure was greater in the biological group (risk ratio 0.30; 95% CI, 0.09 to 0.98, p = 0.035). There was no difference in mid-term valve-related mortality between groups (hazard ratio 0.53; 95% CI, 0.18 to 1.52, p = 0.24). CONCLUSION: The performance of SB valve in septuagenarians seems to be effective with no increased risk of in-hospital mortality, bleeding, or thromboembolic events.

In vitro and in vivo analysis of expression cassettes designed for vascular gene transfer.

Increasing the level and duration of transgene expression and restricting expression to vascular cells are important goals for clinically useful gene therapy vectors. We evaluated several promoters, enhancers and introns in endothelial, smooth muscle and liver cells in tissue culture and in vivo, comparing local delivery to the carotid artery with intravenous delivery to the liver. A 1800-bp fragment of the oxidized LDL receptor (LOX-1) promoter showed highest in vivo activity in the carotid artery, achieving 39% the activity of the reference cytomegalovirus promoter, with 188-fold greater specificity for carotid artery over liver. An enhancer from the Tie2 gene in combination with the intracellular adhesion molecule-2 promoter improved endothelial specificity of plasmid vectors, increased the expression from adenoviral vectors in cultured endothelial cells and doubled the specificity for carotid artery over liver in vivo. Adding a short intron to expression cassettes increased expression in both endothelial and smooth muscle cells in vitro; however, the eNOS enhancer failed to consistently increase the expression or endothelial specificity of the vector. In conclusion, elements from the LOX-1 promoter and Tie2 enhancer together with an intron can be used to improve vectors for vascular gene transfer.

Influence of concomitant coronary artery bypass graft on outcome of surgery of the ascending aorta/arch.

BACKGROUND: Surgery of the ascending aorta with or without arch is being performed in an increasingly elderly population with risks of coexisting coronary artery disease. AIM: To define specific groups requiring coronary artery bypass graft (CABG) and to analyse the influence of concomitant CABG on outcome. DESIGN: Over a 10-year period in a single institution, 296 consecutive procedures on the ascending aorta with or without arch were carried out in 291 patients. CABG was required in 42 (14.2%) procedures. In 24 (57%) patients, CABG was planned preoperatively and in 18 (43%) patients, on a salvage basis. RESULTS: In-hospital mortality for patients undergoing concomitant CABG was higher (21.4% v 11%, p<0.06). Adjusting for baseline and operative characteristics, this was attributable to operative priority, and was not a consequence of concomitant CABG (adjusted OR 0.30, 95% CI 1.1 to 8.31; p = 0.48). However, in-hospital mortality was significantly higher when CABG was performed as salvage rather than as a planned procedure (38.9% v 8.9%, p = 0.025), and this difference remained after adjusting for confounding variables (adjusted OR 16.2, 95% CI 1.03 to >200; p = 0.047). The 3-year survival was significantly lower with concomitant CABG (59% v 81.9%, p<0.001). CONCLUSIONS: In association with surgery of the ascending aorta with or without arch planned concomitant CABG did not entail any added operative risk. However, salvage CABG, which occurred almost exclusively in association with emergency cases, was associated with a higher early mortality. Patients needing concomitant CABG had worse survival at 3 years compared with those requiring isolated surgery of the ascending aorta with or without arch.

Cognitive behavioural therapy in chronic fatigue syndrome: a randomised controlled trial of an outpatient group programme.

OBJECTIVES: To test the hypothesis that group cognitive behavioural therapy (CBT) will produce an effective and cost-effective management strategy for patients in primary care with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME). DESIGN: A double-blind, randomised controlled trial was adopted with three arms. Outcomes were assessed at baseline and 6 and 12 months after first assessment and results were analysed on an intention-to-treat basis. SETTING: A health psychology department for the management of chronic illness in a general hospital in Bristol, UK. PARTICIPANTS: Adults with a diagnosis of CFS/ME referred by their GP. INTERVENTIONS: The three interventions were group CBT incorporating graded activity scheduling, education and support group (EAS) and standard medical care (SMC). OUTCOME MEASURES: The primary outcome measure was the Short Form with 36 Items (SF-36) physical and mental health summary scales. Other outcome measures included the Chalder fatigue scale, Hospital Anxiety and Depression Scale, General Health Questionnaire, physical function (shuttles walked, walking speed and perceived fatigue), health utilities index and cognitive function (mood, recall and reaction times). RESULTS: A total of 153 patients were recruited to the trial and 52 were randomised to receive CBT, 50 to EAS and 51 to SMC. Twelve patients failed to attend for the 12-month follow-up and 19 patients attended one follow-up, but not both. The sample was found to be representative of the patient group and the characteristics of the three groups were similar at baseline. Three outcome measures, SF-36 mental health score, Chalder fatigue scale and walking speed, showed statistically significant differences between the groups. Patients in the CBT group had significantly higher mental health scores [difference +4.35, 95% confidence interval (CI) +0.72 to +7.97, p = 0.019], less fatigue (difference -2.61, 95% CI -4.92 to -0.30, p = 0.027) and were able to walk faster (difference +2.83 shuttles, 95% CI +1.12 to +5.53, p = 0.0013) than patients in the SMC group. CBT patients also walked faster and were less fatigued than those randomised to EAS (walking speed: difference +1.77, 95% CI +0.025 to +3.51, p = 0.047; fatigue: difference -3.16, 95% CI -5.59 to -0.74, p = 0.011). Overall, no other statistically significant difference across the groups was found, although for many measures a trend towards an improved outcome with CBT was seen. Except for walking speed, which, on average, increased by +0.87 shuttles (95% CI +0.09 to +1.65, p = 0.029) between the 6- and 12-month follow-ups, the scores were similar at 6 and 12 months. At baseline, 30% of patients had an SF-36 physical score within the normal range and 52% had an SF-36 mental health score in the normal range. At 12 months, the physical score was in the normal range for 46% of the CBT group, 26% of the EAS group and 44% of SMC patients. For mental health score the percentages were CBT 74%, EAS 67% and SMC 70%. Of the CBT group, 32% showed at least a 15% increase in physical function and 64% achieved a similar improvement in their mental health. For the EAS and SMC groups, this improvement in physical and mental health was achieved for 40 and 60% (EAS) and 49 and 53% (SMC), respectively. The cost-effectiveness of the intervention proved very difficult to assess and did not yield reliable conclusions. CONCLUSIONS: Group CBT did not achieve the expected change in the primary outcome measure as a significant number did not achieve scores within the normal range post-intervention. The treatment did not return a significant number of subjects to within the normal range on this domain; however, significant improvements were evident in some areas. Group CBT was effective in treating symptoms of fatigue, mood and physical fitness in CFS/ME. It was found to be as effective as trials using individual therapy in these domains. However, it did not bring about improvement in cognitive function or quality of life. There was also evidence of improvement in the EAS group, which indicates that there is limited value in the non-specific effects of therapy. Further research is needed to develop better outcome measures, assessments of the broader costs of the illness and a clearer picture of the characteristics best fitted to this type of intervention.

Risk factors for and economic implications of prolonged ventilation after cardiac surgery.

OBJECTIVE: The study's objective was to identify predictors of prolonged ventilation and assess clinical and cost implications in patients undergoing cardiac surgery. METHODS: Patients undergoing cardiac surgery were classified as (1) ventilated less than 96 hours or (2) ventilated 96 hours or more. Multivariate modeling was used to identify predictors of prolonged ventilation and to ascertain the impact of prolonged ventilation on in-hospital mortality and bed occupancy costs and 5-year survival. RESULTS: A total of 7553 patients were studied; 197 (2.6%) had prolonged ventilation. Median ventilation times were 8 and 192 hours, and in-hospital mortality was 1.0% and 22.2% in the control and prolonged ventilation groups, respectively (P < .001). In-hospital mortality remained higher in the prolonged ventilation group after adjustment and when comparing propensity-matched patients (odds ratio 8.06; 95% confidence interval [CI] 4.27-15.2; P < .001 for propensity-matched groups). Independent predictors of prolonged ventilation were as follows: older age, New York Heart Association class, ejection fraction less than 50%, creatinine greater than 200 micromol/L, multiple valve replacements, aortic procedures, operative priority, reoperation for bleeding, inotropes, and preoperative intra-aortic balloon pump. Five-year survival was lower in the prolonged ventilation group (56.1% [95% CI 46.6%-64.6%] vs 88.8% [95% CI 87.9%-89.6%]) also after adjustment for imbalances and when comparing propensity-matched patients (hazard ratio 2.39; 95% CI 1.75-3.27; P < .001 for propensity-matched groups). Mean bed occupancy costs were 14,286 dollars (95% CI 12,731 dollars-15,690 dollars) and 2761 dollars (95% CI 2705 dollars-2814 dollars) in the prolonged ventilation and control groups, respectively (P < .001). CONCLUSION: Prolonged ventilation is associated with high in-hospital mortality and costs, and poor 5-year survival. Identified predictors of prolonged ventilation might help to optimize the clinical management of these patients.

Gamma-ray density and thickness gauges using ultra-low activity radioisotope sourcesfillin.

Most commercial nuclear density gauges use either (137)Cs or (60)Co sources of activity between about 185 and 1850 MBq (5 and 50 mCi). In the current work, density and thickness gauges that use ultra-low activity gamma-ray sources that are exempt from licensing requirements have been investigated. Results are reported on gauges that use a 1 MBq (22)Na source for determining slurry density in the CSIRO UltraPS slurry particle size analyser and for determining belt loading in the CSIRO on-conveyor belt microwave moisture gauge.

Outcome of heart-lung and bilateral sequential lung transplantation for cystic fibrosis: a UK national study.

Cystic fibrosis (CF) patients requiring transplantation for respiratory failure may undergo either heart-lung (HLT) or bilateral sequential lung (BSLT) transplantation. The choice of operation varies between surgeons, centres and countries. The current authors investigated whether operation type influenced outcome in adult CF patients transplanted in the UK between July 1995 and June 2002. Propensity scores for receipt of BSLT versus HLT were derived using logistic regression. Cox regression was used to compare survival. In total, 88 BSLTs and 93 HLTs were identified. Patient characteristics were similar overall, but HLT recipients were more likely to be on long-term oxygen therapy and to have had prior resuscitation. There were 72 deaths (29 BSLT and 43 HLT) within 4 yrs. There was a trend towards higher unadjusted survival following BSLT, but, after adjustment, no difference was found (hazard ratio = 0.77; 95% confidence interval 0.29-2.06). Time to the first rejection episode and infection rates were also similar. A total of 82% of hearts from HLT recipients were used as domino heart transplants. In conclusion, after adjusting for comorbidity, donor factors and ischaemia time, it was found that heart-lung and bilateral sequential lung transplantation achieved a similar outcome. The use of domino heart transplantation ameliorated the impact of heart-lung transplantation on total organ availability.