Creating therapeutic relationships through communication: a qualitative metasynthesis from the perspectives of people with communication impairment after stroke.

PURPOSE: Communication between patients and clinicians influences the development of therapeutic relationships. Communication is disrupted when the patient has communication impairments after stroke. However, how these communication disruptions influence therapeutic relationships is not well-understood. This qualitative metasynthesis explores the perspectives of people with communication impairment to understand how interpersonal communication influences therapeutic relationships. MATERIAL AND METHODS: Four databases were searched for qualitative studies which discussed how communication influenced therapeutic relationships from the perspectives of people with aphasia, dysarthria or apraxia of speech. Additional papers were identified through citation searching and subject experts. Nineteen eligible papers were included and analysed using thematic analysis. RESULTS: Four themes were constructed from the analysis: (1) Relationships provide the foundation for rehabilitation; (2) Different relational possibilities arise from "reading" the clinician; (3) Creating therapeutic relationships through validating interactions and connections; and (4) Creating therapeutic disconnections through invalidating, exclusionary interactions. CONCLUSIONS: A therapeutic relationship develops, at least in part, in response to the clinician's communication and how this is received and experienced by the patient. Understanding the characteristics of relationship-fostering communication and knowing how communication influences relationships can help clinicians critically reflect on their communication and better develop therapeutic relationships with people with communication impairment.IMPLICATIONS FOR REHABILITATIONPractitioner-patient communication can facilitate therapeutic relationships or create therapeutic disconnections.Communication patterns that are commonly evident when a patient has communication impairments can impede therapeutic relationships.Clinicians need to attend to how their communication is received and how it influences people's sense of self.Communication partner training should address the existential and relational needs of people with communication impairment after stroke.

Multi-omic analysis of the effects of low frequency ventilation during cardiopulmonary bypass surgery.

BACKGROUND: Heart surgery with cardio-pulmonary bypass (CPB) is associated with lung ischemia leading to injury and inflammation. It has been suggested this is a result of the lungs being kept deflated throughout the duration of CPB. Low frequency ventilation (LFV) during CPB has been proposed to reduce lung dysfunction. METHODS: We used a semi-biased multi-omic approach to analyse lung biopsies taken before and after CPB from 37 patients undergoing coronary artery bypass surgery randomised to both lungs left collapsed or using LFV for the duration of CPB. We also examined inflammatory and oxidative stress markers from blood samples from the same patients. RESULTS: 30 genes were induced when the lungs were left collapsed and 80 by LFV. Post-surgery 26 genes were significantly higher in the LFV vs. lungs left collapsed, including genes associated with inflammation (e.g. IL6 and IL8) and hypoxia/ischemia (e.g. HIF1A, IER3 and FOS). Relatively few changes in protein levels were detected, perhaps reflecting the early time point or the importance of post-translational modifications. However, pathway analysis of proteomic data indicated that LFV was associated with increased "cellular component morphogenesis" and a decrease in "blood circulation". Lipidomic analysis did not identify any lipids significantly altered by either intervention. DISCUSSION: Taken together these data indicate the keeping both lungs collapsed during CPB significantly induces lung damage, oxidative stress and inflammation. LFV during CPB increases these deleterious effects, potentially through prolonged surgery time, further decreasing blood flow to the lungs and enhancing hypoxia/ischemia.

Evaluation of an early-stage innovation for full-thickness excision of benign colonic polyps using the IDEAL framework.

AIMS: Colectomy is the current approach for patients with endoscopically unresectable benign polyps but risks considerable morbidity. Full-thickness laparoendoscopic excision (FLEX) is a novel procedure, specifically developed to treat endoscopically unresectable benign colonic polyps, which could reduce the treatment burden of the current approach and improve outcomes. However, traditional evaluations of surgical innovations lack methodological rigour. This study reports the development and feasibility of the FLEX procedure in selected patients. METHOD: A prospective development study using the Idea, Development, Evaluation, Assessment, Long-term study (IDEAL) framework was undertaken, by one surgeon, of the FLEX procedure in selected patients with endoscopically unresectable benign colonic polyps. Three-dimensional (3D)-CT colonography reconstructions were used preoperatively to rehearse patient-specific, critical manoeuvres. Targetted, full-thickness excision was performed: after marking the margin of the caecal polyp using circumferential endoscopic argon plasma coagulation, transmural endoscopic sutures were used to evert the bowel and resection was undertaken by laparoscopic linear stapling. Feasibility outcomes (establishing 'local success') included evidence of complete polyp resection without adverse events (especially safe closure of the excision site). RESULTS: Ten patients [median (interquartile range) age: 74 (59-78) years] with polyp median diameters of 35 (30-41) mm, were referred for and consented to receive the FLEX procedure. During the same time frame, no patient underwent colectomy for benign polyps. One further patient received FLEX for local excision of a presumed malignant polyp because severe comorbidity prohibited standard procedures. The FLEX procedure was successfully performed locally, with complete resection of the polyp and safe closure of the excision site, in eight patients. Three noncompleted procedures were converted to laparoscopic segmental colectomy under the same anaesthetic because of endoscopic inaccessibility (two patients) and transcolonic suture failure (one patient). CONCLUSIONS: The FLEX procedure is still under development. Early data demonstrate that it is safe for excision of selected benign polyps. Modifications to transcolonic suture delivery are now required and there is a need for wider adoption before more definitive evaluation can be performed.

Towards speciation of organically bound tritium and deuterium: Quantification of non-exchangeable forms in carbohydrate molecules.

An original methodology to quantitatively explore exchangeability of hydrogen isotopes in carbohydrate molecules is proposed. To access the speciation of organically bound hydrogen isotopes, isotopic exchanges were carried out under a soft path regime in the vapor phase at 20 °C with set (D,T/H) vapor pressure ratios. When steady states were reached, the fraction of exchangeable hydrogen of microcrystalline cellulose, alpha-cellulose and wheat grains were obtained and ranged from 13 to 31% (versus a theoretical value of 30%). In cellulose, and more specifically in microcrystalline cellulose, the molecular hydrogen bonds as well as the different conformations of the network seemed to decrease the hydroxyl groups of glucose units available for isotopic exchange. On the contrary, the assumed enzymatic hydrolysis of the constitutive molecules of wheat starch into low-molecular weight carbohydrate molecules enhanced the exchangeable pool. An average value of the activity between non-exchangeable organically bound tritium (NE-OBT) and non-exchangeable organically bound hydrogen was calculated for wheat grains, (TH)NE  = 0.55 ±â€¯0.03 Bq.g-1 of hydrogen atoms.

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.

New insight into the ternary complexes of uranyl carbonate in seawater.

Uranium is naturally present in seawater at trace levels and may in some cases be present at higher concentrations, due to anthropogenic nuclear activities. Understanding uranium speciation in seawater is thus essential for predicting and controlling its behavior in this specific environmental compartment and consequently, its possible impact on living organisms. The carbonato calcic complex Ca2UO2(CO3)3 was previously identified as the main uranium species in natural seawater, together with CaUO2(CO3)32-. In this work, we further investigate the role of the alkaline earth cation in the structure of the ternary uranyl-carbonate complexes. For this purpose, artificial seawater, free of Mg2+ and Ca2+, using Sr2+ as a spectroscopic probe was prepared. Combining TRLIF and EXAFS spectroscopy, together with DFT and theoretical thermodynamic calculations, evidence for the presence of Sr alkaline earth counter ion in the complex structure can be asserted. Furthermore, data suggest that when Ca2+ is replaced by Sr2+, SrUO2(CO3)32- is the main complex in solution and it occurs with the presence of at least one monodentate carbonate in the uranyl coordination sphere.

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/).

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.

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.

Health professionals' and service users' perspectives of shared care for monitoring wet age-related macular degeneration: a qualitative study alongside the ECHoES trial.

OBJECTIVES: To explore the views of eye health professionals and service users on shared community and hospital care for wet or neovascular age-related macular degeneration (nAMD). METHOD: Using maximum variation sampling, 5 focus groups and 10 interviews were conducted with 23 service users and 24 eye health professionals from across the UK (consisting of 8 optometrists, 6 ophthalmologists, 6 commissioners, 2 public health representatives and 2 clinical eye care advisors to local Clinical Commissioning Groups). Data were transcribed verbatim and analysed thematically using constant comparative techniques derived from grounded theory methodology. RESULTS: The needs and preferences of those with nAMD appear to be at odds with the current service being provided. There was enthusiasm among health professionals and service users about the possibility of shared care for nAMD as it was felt to have the potential to relieve hospital eye service burden and represent a more patient-centred option, but there were a number of perceived barriers to implementation. Some service users and ophthalmologists voiced concerns about optometrist competency and the potential for delays with referrals to secondary care if stable nAMD became active again. The health professionals were divided as to whether shared care was financially more efficient than the current model of care. Specialist training for optometrists, under the supervision of ophthalmologists, was deemed to be the most effective method of training and was perceived to have the potential to improve the communication and trust that shared care would require. CONCLUSIONS: While shared care is perceived to represent a promising model of nAMD care, voiced concerns suggest that there would need to be greater collaboration between ophthalmology and optometry, in terms of interprofessional trust and communication. TRIAL REGISTRATION NUMBER: ISRCTN07479761.

Synthesis and investigation of cobalt chalcogenide clusters with thienyl phosphine ligands as new acceptor materials for P3HT.

Cobalt selenide clusters with 2-bromo-5-diethylphosphinothiophene (1) and 2-bromo-5-diphenylphosphinothiophene (2) ligands are described. The phosphine ligands are obtained via lithium halogen exchange of 2,5-dibromothiophene followed by addition of chlorodiethylphosphine and chlorodiphenylphosphine, respectively. The prepared phosphine ligands are then sequentially reacted with elemental selenium followed by dicobalt octacarbonyl to yield Co6Se8(P(Et)2(C4H2SBr))6 (3) or Co6Se8(P(Ph)2(C4H2SBr))6 (4), respectively. The two new cobalt selenide clusters were characterized by UV-visible spectroscopy, Fourier-transform infrared spectroscopy, cyclic voltammetry, powder X-ray diffraction, and elemental analysis. Emission spectra were recorded for the addition of, Co6Se8(PEt3)6 (5), 3, and 4 to a 0.004 wt% solution of poly-3-hexyl thiophene (P3HT) in toluene to investigate the charge transport of the system. The quenching of the polymers' emission follows first-order like decay for each cluster. Clusters 3 and 4 are approximately twice as efficient at quenching the emission than cluster 5 with 4 being slightly more efficient than 3. Simple mixtures of 3, 4 or 5 and P3HT were spun cast from toluene into thin films and atomic force microscopy displayed relatively uniform dispersion of 3 and network-like formation of 4 in contrast to the phase separation of 5 in the polymer films.

Conversion of S-phenylsulfonylcysteine residues to mixed disulfides at pH 4.0: utility in protein thiol blocking and in protein-S-nitrosothiol detection.

A three step protocol for protein S-nitrosothiol conversion to fluorescent mixed disulfides with purified proteins, referred to as the thiosulfonate switch, is explored which involves: (1) thiol blocking at pH 4.0 using S-phenylsulfonylcysteine (SPSC); (2) trapping of protein S-nitrosothiols as their S-phenylsulfonylcysteines employing sodium benzenesulfinate; and (3) tagging the protein thiosulfonate with a fluorescent rhodamine based probe bearing a reactive thiol (Rhod-SH), which forms a mixed disulfide between the probe and the formerly S-nitrosated cysteine residue. S-Nitrosated bovine serum albumin and the S-nitrosated C-terminally truncated form of AdhR-SH (alcohol dehydrogenase regulator) designated as AdhR*-SNO were selectively labelled by the thiosulfonate switch both individually and in protein mixtures containing free thiols. This protocol features the facile reaction of thiols with S-phenylsulfonylcysteines forming mixed disulfides at mild acidic pH (pH = 4.0) in both the initial blocking step as well as in the conversion of protein-S-sulfonylcysteines to form stable fluorescent disulfides. Labelling was monitored by TOF-MS and gel electrophoresis. Proteolysis and peptide analysis of the resulting digest identified the cysteine residues containing mixed disulfides bearing the fluorescent probe, Rhod-SH.

Treatment decisions for descending thoracic aneurysm: preferences for thoracic endovascular aneurysm repair or surveillance in a discrete choice experiment.

OBJECTIVE: To investigate and rank factors that influence endovascular treatment decisions by specialists for patients with descending thoracic aortic aneurysm (dTAA). METHODS: Specialists completed a diagrammatic survey describing uncertainty about the benefit of thoracic endovascular aneurysm repair (TEVAR) for dTAA with respect to age, sex, and aneurysm diameter. Subsequently, a detailed discrete choice experiment was designed. Specialists were recruited and asked to indicate treatment their preference (TEVAR or surveillance) in 25 hypothetical cases of dTAA, with variable patient attributes: age, sex, American Society of Anesthesiologists (ASA) grade, aneurysm diameter, adequate landing zone distal to left subclavian artery (LSA), and length of aortic coverage. Data were analysed using multiple logistic regression. RESULTS: The diagrammatic survey, based on 50 respondents, showed that uncertainty about the benefits of TEVAR was greatest for patients aged 80-85 years (up to 47% of respondents were "unsure") and that uncertainty increased with increasing aneurysm diameter (for an 80-year-old man, 7% were unsure at 5.5 cm and 33% were unsure at 7.0 cm). Seventy-one specialists (mainly from Europe and North America, 86% vascular surgeons and 98% working in units offering TEVAR) completed the discrete choice experiment. Preference for TEVAR increased greatly with enlarging diameter: adjusted odds ratios (OR) >5.5-6.0 cm = 15.8 (95% confidence interval [CI] 9.83-25.40); >6.0-6.5 cm = 393.0 (95% CI 202.00-766.00); >6.5-7.0 cm = 1829.0 (95% CI 400.00-4,181.00). TEVAR was less likely to be preferred in patients older than 75 years (>75-80 years OR 0.32, 95% CI 0.21-0.49; >80-85 years = 0.18, 95% CI 0.11-0.28); in women (OR 0.52, 95% CI 0.37-0.74); in patients classified as ASA grade 4 (OR 0.44, 95% CI 0.36-0.57); and in patients with aorta coverage >25 cm (OR 0.48, 95% CI 0.32-0.74). The proximal landing zone did not influence preference. CONCLUSION: Specialists' preferences for endovascular repair of degenerative dTAA vary widely, and demonstrate clinical uncertainty, especially in octogenarians, and a reluctance to offer TEVAR to women. Aneurysm diameter dominates treatment preferences, but patient fitness and length of aortic coverage (>25 cm) also were influential, although the landing zone distal to LSA was not.

Verteporfin photodynamic therapy for neovascular age-related macular degeneration: cohort study for the UK.

OBJECTIVES: The verteporfin photodynamic therapy (VPDT) cohort study aimed to answer five questions: (a) is VPDT in the NHS provided as in randomised trials?; (b) is 'outcome' the same in the nhs as in randomised trials?; (c) is 'outcome' the same for patients ineligible for randomised trials?; (d) is VPDT safe when provided in the NHS?; and (e) how effective and cost-effective is VPDT? DESIGN: Treatment register. SETTING: All hospitals providing VPDT in the NHS. PARTICIPANTS: All patients attending VPDT clinics. INTERVENTIONS: Infusion of verteporfin followed by infrared laser exposure is called VPDT, and is used to treat neovascular age-related macular degeneration (nAMD). The VPDT cohort study advised clinicians to follow patients every 3 months during treatment or active observation, retreating based on criteria used in the previous commercial 'TAP' (Treatment of Age-related macular degeneration with Photodynamic therapy) trials of VPDT. MAIN OUTCOME MEASURES: The primary outcome was logarithm of the minimum angle of resolution monocular best-corrected distance visual acuity (BCVA). Secondary outcomes were adverse reactions and events; morphological changes in treated nAMD (wet) lesions; and for a subset of patients, 6-monthly contrast sensitivity, generic and visual health-related quality of life (HRQoL) and resource use. Treated eyes were classified as eligible for the TAP trials (EFT), ineligible (IFT) or unclassifiable (UNC). RESULTS: Forty-seven hospitals submitted data for 8323 treated eyes in 7748 patients; 4919 eyes in 4566 patients were treated more than 1 year before the last data submission or had completed treatment. Of 4043 eyes with nAMD in 4043 patients, 1227 were classified as EFT, 1187 as IFT and 1629 as UNC. HRQoL and resource use data were available for about 2000 patients. The mean number of treatments in years 1 and 2 was 2.3 and 0.4 respectively. About 50% of eyes completed treatment within 1 year. BCVA deterioration in year 1 did not differ between eligibility groups. EFT eyes lost 11.6 letters (95% confidence interval 10.1 to 13.0 letters) compared with 9.9 letters in VPDT-treated eyes in the TAP trials. EFT eyes had poorer BCVA at baseline than IFT and UNC eyes. Adverse reactions and events were reported for 1.4% of first visits - less frequently than those reported in the TAP trials. Associations between BCVA in the best-seeing eye with HRQoL and community health and social care resource use showed that the 11-letter difference in BCVA between VPDT and sham treatment in the TAP trials corresponded to differences in utility of 0.012 and health and social service costs of £60 and £92 in years 1 and 2, respectively. VPDT provided an incremental cost per quality-adjusted life-year (QALY) of £170,000 over 2 years. CONCLUSIONS: VPDT was administered less frequently than in the TAP trials, with less than half of those treated followed up for > 1 year in routine clinical practice. Deterioration in BCVA over time in EFT eyes was similar to that in the TAP trials. The similar falls in BCVA after VPDT across the pre-defined TAP eligibility groups do not mean that the treatment is equally effective in these groups because deterioration in BCVA can be influenced by the parameters that determined group membership. Safety was no worse than in the TAP trials. The estimated cost per QALY was similar to the highest previous estimate. Although VPDT is no longer in use as monotherapy for neovascular AMD, its role as adjunctive treatment has not been fully explored. VPDT also has potential as monotherapy in the management of vascular malformations of the retina and choroid and with trials underway in neovascularisation due to myopia and polypoidal choroidopathy. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Identification of risk factors by systematic review and development of risk-adjusted models for surgical site infection.

BACKGROUND: Surgical site infections (SSIs) are complications of surgery that cause significant postoperative morbidity. SSI has been proposed as a potential indicator of the quality of care in the context of clinical governance and monitoring of the performance of NHS organisations against targets. OBJECTIVES: We aimed to address a number of objectives. Firstly, identify risk factors for SSI, criteria for stratifying surgical procedures and evidence about the importance of postdischarge surveillance (PDS). Secondly, test the importance of risk factors for SSI in surveillance databases and investigate interactions between risk factors. Thirdly, investigate and validate different definitions of SSI. Lastly, develop models for making risk-adjusted comparisons between hospitals. DATA SOURCES: A single hospital surveillance database was used to address objectives 2 and 3 and the UK Surgical Site Infection Surveillance Service database to address objective 4. STUDY DESIGN: There were four elements to the research: (1) systematic reviews of risk factors for SSI (two reviewers assessed titles and abstracts of studies identified by the search strategy and the quality of studies was assessed using the Newcastle Ottawa Scale); (2) assessment of agreement between four SSI definitions; (3) validation of definitions of SSI, quantifying their ability to predict clinical outcomes; and (4) development of operation-specific risk models for SSI, with hospitals fitted as random effects. RESULTS: Reviews of SSI risk factors other than established SSI risk indices identified other risk; some were operation specific, but others applied to multiple operations. The factor most commonly identified was duration of preoperative hospital stay. The review of PDS for SSI confirmed the need for PDS if SSIs are to be compared meaningfully over time within an institution. There was wide variation in SSI rate (SSI%) using different definitions. Over twice as many wounds were classified as infected by one definition only as were classified as infected by both. Different SSI definitions also classified different wounds as being infected. The two most established SSI definitions had broadly similar ability to predict the chosen clinical outcomes. This finding is paradoxical given the poor agreement between definitions. Elements of each definition not common to both may be important in predicting clinical outcomes or outcomes may depend on only a subset of elements which are common to both. Risk factors fitted in multivariable models and their effects, including age and gender, varied by surgical procedure. Operative duration was an important risk factor for all operations, except for hip replacement. Wound class was included least often because some wound classes were not applicable to all operations or were combined because of small numbers. The American Association of Anesthesiologists class was a consistent risk factor for most operations. CONCLUSIONS: The research literature does not allow surgery-specific or generic risk factors to be defined. SSI definitions varied between surveillance programmes and potentially between hospitals. Different definitions do not have good agreement, but the definitions have similar ability to predict outcomes influenced by SSI. Associations between components of the National Nosocomial Infections Surveillance risk index and odds of SSI varied for different surgical procedures. There was no evidence for effect modification by hospital. Estimates of SSI% should be disseminated within institutions to inform infection control. Estimates of SSI% across institutions or countries should be interpreted cautiously and should not be assumed to reflect quality of medical care. Future research should focus on developing an SSI definition that has satisfactory psychometric properties, that can be applied in everyday clinical settings, includes PDS and is formulated to detect SSIs that are important to patients or health services. FUNDING: The National Institute for Health Research Technology Assessment programme.

The Patients Preferences Questionnaire for Angina treatment: results and psychometrics from 383 patients in primary care in England.

OBJECTIVES: To develop a psychometrically valid Patient Preferences Questionnaire for Angina treatment (PPQA). SETTING: Seven general practices across England in 2007. SUBJECTS: Convenience sample of 383 patients with diagnosed angina. METHOD: Postal self-administered questionnaire survey using the full-length PPQA. This comprised 54 items about the three main treatment modalities for angina: medication, angioplasty and coronary artery bypass grafting. RESULTS: The full PPQA was reduced to 18 items, six for each of the three subscales (treatment modalities), by standard psychometric methods. The reduced PPQA was psychometrically sound and valid, although confirmatory factor analyses with a larger sample are required. CONCLUSION: The PPQA is a potentially useful instrument to help clinicians understand patients' angina treatment preferences.

Predicting mortality for patients with exacerbations of COPD and Asthma in the COPD and Asthma Outcome Study (CAOS).

INTRODUCTION: Decisions about the intensity of treatment for patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are influenced by predictions about survival and quality of life. Evidence suggests that these predictions are poorly calibrated and tend to be pessimistic. AIM: The aim of this study was to develop an outcome prediction model for COPD patients to support treatment decisions. METHODS: A prospective multi-centre cohort study in Intensive Care Units (ICU) and Respiratory High Dependency Units (RHDU) in the UK recruited patients aged 45 years and older admitted with an exacerbation of obstructive lung disease. Data were collected on patients' characteristics prior to ICU admission, and on their survival and quality of life after 180 days. An outcome prediction model was developed using multivariate logistic regression and bootstrapping. RESULTS: Ninety-two ICUs (53% of those in the UK) and three RHDUs took part. A total of 832 patients were recruited. Cumulative 180-day mortality was 37.9%. Using data available at the time of admission to the units, a prognostic model was developed which had an estimated area under the receiver operating characteristic curve ('c') of 74.7% after bootstrapping that was more discriminating than the clinicians (P = 0.033) and was well calibrated. DISCUSSION: This study has produced an outcome prediction model with slightly better discrimination and much better calibration than the participating clinicians. It has the potential to support risk adjustment and clinical decision making about admission to intensive care.