Guiqing Yao

Computed tomographic colonography versus colonoscopy for investigation of patients with symptoms suggestive of colorectal cancer (SIGGAR): a multicentre randomised trial

BACKGROUND Colonoscopy is the gold-standard test for investigation of symptoms suggestive of colorectal cancer; computed tomographic colonography (CTC) is an alternative, less invasive test. However, additional investigation after CTC is needed to confirm suspected colonic lesions, and this is an important factor in establishing the feasibility of CTC as an alternative to colonoscopy. We aimed to compare rates of additional colonic investigation after CTC or colonoscopy for detection of colorectal cancer or large (≥10 mm) polyps in symptomatic patients in clinical practice. METHODS This pragmatic multicentre randomised trial recruited patients with symptoms suggestive of colorectal cancer from 21 UK hospitals. Eligible patients were aged 55 years or older and regarded by their referring clinician as suitable for colonoscopy. Patients were randomly assigned (2:1) to colonoscopy or CTC by computer-generated random numbers, in blocks of six, stratified by trial centre and sex. We analysed the primary outcome-the rate of additional colonic investigation-by intention to treat. The trial is an International Standard Randomised Controlled Trial, number 95152621. FINDINGS 1610 patients were randomly assigned to receive either colonoscopy (n=1072) or CTC (n=538). 30 patients withdrew consent, leaving for analysis 1047 assigned to colonoscopy and 533 assigned to CTC. 160 (30.0%) patients in the CTC group had additional colonic investigation compared with 86 (8.2%) in the colonoscopy group (relative risk 3.65, 95% CI 2.87-4.65; p<0.0001). Almost half the referrals after CTC were for small (<10 mm) polyps or clinical uncertainty, with low predictive value for large polyps or cancer. Detection rates of colorectal cancer or large polyps in the trial cohort were 11% for both procedures. CTC missed 1 of 29 colorectal cancers and colonoscopy missed none (of 55). Serious adverse events were rare. INTERPRETATION Guidelines are needed to reduce the referral rate after CTC. For most patients, however, CTC provides a similarly sensitive, less invasive alternative to colonoscopy. FUNDING NIHR Health Technology Assessment Programme, NIHR Biomedical Research Centres funding scheme, Cancer Research UK, EPSRC Multidisciplinary Assessment of Technology Centre for Healthcare, and NIHR Collaborations for Leadership in Applied Health Research and Care.

Cost-effectiveness of cardiac resynchronization therapy: results from the CARE-HF trial

AIMS Whilst the CArdiac REsynchronization in Heart Failure (CARE-HF) trial has shown that cardiac resynchronization therapy (CRT) leads to reduced morbidity and mortality, the cost-effectiveness of this therapy remains uncertain. The aim of this study was to evaluate the incremental cost per quality adjusted life year (QALY) gained and incremental cost per life year gained of CRT plus medical therapy compared to medical therapy alone. METHODS AND RESULTS This prospective analysis based on intention to treat data from all patients enrolled in the CARE-HF trial at 82 clinical centres in 12 European countries. A total of 813 patients with New York Heart Association class III or IV heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony were randomized to CRT plus medical therapy (n = 409) vs. medical therapy alone (n = 404). During a mean follow-up of 29.4 months CRT was associated with increased costs (4316, 95% CI: 1327-7485), survival (0.10 years, 95% CI: -0.01-0.21), and QALYs (0.22, 95% CI: 0.13-0.32). The incremental cost-effectiveness ratio was 19 319 per QALY gained (95% CI: 5482-45 402) and 43 596 per life-year gained (95% CI: -146 236-223 849). These results were sensitive to the costs of the device, procedure, and hospitalization. CONCLUSION Treatment with CRT appears cost-effective at the notional willingness to pay threshold of 29 400 (20,000 pounds sterlings) per QALY gained.

Computed tomographic colonography versus barium enema for diagnosis of colorectal cancer or large polyps in symptomatic patients (SIGGAR): a multicentre randomised trial

BACKGROUND Barium enema (BE) is widely available for diagnosis of colorectal cancer despite concerns about its accuracy and acceptability. Computed tomographic colonography (CTC) might be a more sensitive and acceptable alternative. We aimed to compare CTC and BE for diagnosis of colorectal cancer or large polyps in symptomatic patients in clinical practice. METHODS This pragmatic multicentre randomised trial recruited patients with symptoms suggestive of colorectal cancer from 21 UK hospitals. Eligible patients were aged 55 years or older and regarded by their referring clinician as suitable for radiological investigation of the colon. Patients were randomly assigned (2:1) to BE or CTC by computer-generated random numbers, in blocks of six, stratified by trial centre and sex. We analysed the primary outcome-diagnosis of colorectal cancer or large (≥10 mm) polyps-by intention to treat. The trial is an International Standard Randomised Controlled Trial, number 95152621. FINDINGS 3838 patients were randomly assigned to receive either BE (n=2553) or CTC (n=1285). 34 patients withdrew consent, leaving for analysis 2527 assigned to BE and 1277 assigned to CTC. The detection rate of colorectal cancer or large polyps was significantly higher in patients assigned to CTC than in those assigned to BE (93 [7.3%] of 1277 vs 141 [5.6%] of 2527, relative risk 1.31, 95% CI 1.01-1.68; p=0.0390). CTC missed three of 45 colorectal cancers and BE missed 12 of 85. The rate of additional colonic investigation was higher after CTC than after BE (283 [23.5%] of 1206 CTC patients had additional investigation vs 422 [18.3%] of 2300 BE patients; p=0.0003), due mainly to a higher polyp detection rate. Serious adverse events were rare. INTERPRETATION CTC is a more sensitive test than BE. Our results suggest that CTC should be the preferred radiological test for patients with symptoms suggestive of colorectal cancer. FUNDING NIHR Health Technology Assessment Programme, NIHR Biomedical Research Centres funding scheme, Cancer Research UK, EPSRC Multidisciplinary Assessment of Technology Centre for Healthcare, and NIHR Collaborations for Leadership in Applied Health Research and Care.

A Systematic Review of the Incidence and Prevalence of Long-Term Neurological Conditions in the UK

Background: Updated, robust estimates of the incidence and prevalence of rare long-term neurological conditions in the UK are not available. Global estimates may be misrepresentative as disease aetiology may vary by location. Objectives: To systematically review the incidence and prevalence of long-term neurological conditions in the UK since 1988. Search Strategy: Medline (January 1988 to January 2009), Embase (January 1988 to January 2009), CINAHL (January 1988 to January 2009) and Cochrane CENTRAL databases. Selection Criteria: UK population-based incidence/prevalence studies of long-term neurological conditions since 1988. Exclusion criteria included inappropriate diagnoses and incomprehensive case ascertainment. Data Collection and Analysis: Articles were included based on the selection criteria. Data were extracted from articles with ranges of incidence and prevalence reported. Main Results: Eight studies met the criteria (3 on motor neurone disease; 4 on Huntington’s disease; 1 on progressive supranuclear palsy). The incidence of motor neurone disease ranged from 1.06 to 2.4/100,000 person-years. The prevalence ranged from 4.02 to 4.91/100,000. The prevalence of Huntington’s disease ranged from 4.0 to 9.94/100,000. The prevalence of progressive supranuclear palsy ranged from 3.1 to 6.5/100,000. Conclusions: The review updates the incidence/prevalence of long-term neurological conditions. Future epidemiological studies must incorporate comprehensive case ascertainment methods and strict diagnostic criteria.

An internet-delivered handwashing intervention to modify influenza-like illness and respiratory infection transmission (PRIMIT): a primary care randomised trial

BACKGROUND Handwashing to prevent transmission of respiratory tract infections (RTIs) has been widely advocated, especially during the H1N1 pandemic. However, the role of handwashing is debated, and no good randomised evidence exists among adults in non-deprived settings. We aimed to assess whether an internet-delivered intervention to modify handwashing would reduce the number of RTIs among adults and their household members. METHODS We recruited individuals sharing a household by mailed invitation through general practices in England. After consent, participants were randomised online by an automated computer-generated random number programme to receive either no access or access to a bespoke automated web-based intervention that maximised handwashing intention, monitored handwashing behaviour, provided tailored feedback, reinforced helpful attitudes and norms, and addressed negative beliefs. We enrolled participants into an additional cohort (randomised to receive intervention or no intervention) to assess whether the baseline questionnaire on handwashing would affect handwashing behaviour. Participants were not masked to intervention allocation, but statistical analysis commands were constructed masked to group. The primary outcome was number of episodes of RTIs in index participants in a modified intention-to-treat population of randomly assigned participants who completed follow-up at 16 weeks. This trial is registered with the ISRCTN registry, number ISRCTN75058295. FINDINGS Across three winters between Jan 17, 2011, and March 31, 2013, we enrolled 20,066 participants and randomly assigned them to receive intervention (n=10,040) or no intervention (n=10,026). 16,908 (84%) participants were followed up with the 16 week questionnaire (8241 index participants in intervention group and 8667 in control group). After 16 weeks, 4242 individuals (51%) in the intervention group reported one or more episodes of RTI compared with 5135 (59%) in the control group (multivariate risk ratio 0·86, 95% CI 0·83-0·89; p<0·0001). The intervention reduced transmission of RTIs (reported within 1 week of another household member) both to and from the index person. We noted a slight increase in minor self-reported skin irritation (231 [4%] of 5429 in intervention group vs 79 [1%] of 6087 in control group) and no reported serious adverse events. INTERPRETATION In non-pandemic years, an effective internet intervention designed to increase handwashing could have an important effect in reduction of infection transmission. In view of the heightened concern during a pandemic and the likely role of the internet in access to advice, the intervention also has potential for effective implementation during a pandemic. FUNDING Medical Research Council.

An internet-based intervention with brief nurse support to manage obesity in primary care (POWeR+): a pragmatic, parallel-group, randomised controlled trial

BACKGROUND The obesity epidemic has major public health consequences. Expert dietetic and behavioural counselling with intensive follow-up is effective, but resource requirements severely restrict widespread implementation in primary care, where most patients are managed. We aimed to estimate the effectiveness and cost-effectiveness of an internet-based behavioural intervention (POWeR+) combined with brief practice nurse support in primary care. METHODS We did this pragmatic, parallel-group, randomised controlled trial at 56 primary care practices in central and south England. Eligible adults aged 18 years or older with a BMI of 30 kg/m(2) or more (or ≥28 kg/m(2) with hypertension, hypercholesterolaemia, or diabetes) registered online with POWeR+-a 24 session, web-based, weight management intervention lasting 6 months. After registration, the website automatically randomly assigned patients (1:1:1), via computer-generated random numbers, to receive evidence-based dietetic advice to swap foods for similar, but healthier, choices and increase fruit and vegetable intake, in addition to 6 monthly nurse follow-up (control group); web-based intervention and face-to-face nurse support (POWeR+Face-to-face [POWeR+F]; up to seven nurse contacts over 6 months); or web-based intervention and remote nurse support (POWeR+Remote [POWeR+R]; up to five emails or brief phone calls over 6 months). Participants and investigators were masked to group allocation at the point of randomisation; masking of participants was not possible after randomisation. The primary outcome was weight loss averaged over 12 months. We did a secondary analysis of weight to measure maintenance of 5% weight loss at months 6 and 12. We modelled the cost-effectiveness of each intervention. We did analysis by intention to treat, with multiple imputation for missing data. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN21244703. FINDINGS Between Jan 30, 2013, and March 20, 2014, 818 participants were randomly assigned to the control group (n=279), the POWeR+F group (n=269), or the POWeR+R group (n=270). Weight loss averaged over 12 months was recorded in 666 (81%) participants. The control group lost almost 3 kg over 12 months (crude mean weight: baseline 104·38 kg [SD 21·11; n=279], 6 months 101·91 kg [19·35; n=136], 12 months 101·74 kg [19·57; n=227]). The primary imputed analysis showed that compared with the control group, patients in the POWeR+F group achieved an additional weight reduction of 1·5 kg (95% CI 0·6-2·4; p=0·001) averaged over 12 months, and patients in the POWeR+R group achieved an additional 1·3 kg (0·34-2·2; p=0·007). 21% of patients in the control group had maintained a clinically important 5% weight reduction at month 12, compared with 29% of patients in the POWeR+F group (risk ratio 1·56, 0·96-2·51; p=0·070) and 32% of patients in the POWeR+R group (1·82, 1·31-2·74; p=0·004). The incremental overall cost to the health service per kg weight lost with the POWeR+ interventions versus the control strategy was £18 (95% CI -129 to 195) for POWeR+F and -£25 (-268 to 157) for POWeR+R; the probability of being cost-effective at a threshold of £100 per kg lost was 88% and 98%, respectively. No adverse events were reported. INTERPRETATION Weight loss can be maintained in some individuals by use of novel written material with occasional brief nurse follow-up. However, more people can maintain clinically important weight reductions with a web-based behavioural program and brief remote follow-up, with no increase in health service costs. Future research should assess the extent to which clinically important weight loss can be maintained beyond 1 year. FUNDING Health Technology Assessment Programme of the National Institute for Health Research.

Long-Term Cost-Effectiveness Analysis of Nebivolol Compared with Standard Care in Elderly Patients with Heart Failure An Individual Patient-Based Simulation Model

AbstractBackground and objective: The SENIORS trial demonstrated that nebivolol is effective in the treatment of heart failure in elderly patients (e.g. ≥70 years). This analysis evaluates the cost effectiveness of nebivolol compared with standard treatment. Methods: An individual patient-simulation model based on a Markov modelling framework was developed to compare costs and outcomes for nebivolol and standard care in patients with heart failure starting treatment at the age of 70 years. Health states were defined by New York Heart Association (NYHA) class and death. At a given NYHA class and a given cycle, patients could die, be hospitalized for cardiovascular disease or remain stable. Risks for these events were derived from individual patient data from the SENIORS trial. The risk of each event in a given cycle was based on the subject’s baseline characteristics and time in the current health state.The economic analysis was conducted from the UK NHS perspective with a lifetime horizon. The costs (€; year 2006 values) considered were drug costs for nebivolol and other cardiac drugs, costs of GP visits, outpatient specialist visits and cardiovascular-related hospitalizations. Univariate and probabilistic sensitivity analysis was conducted. Results: In the baseline analysis, the total cost per patient was €6740 and €9288, and QALYs were 5.194 and 5.843 for patients aged 70 years at the start of treatment for the standard treatment and nebivolol groups, respectively. The probabilistic sensitivity analysis provided an incremental cost-effectiveness ratio of €3926 (95% CI 3731, 4159) per QALY. Conclusions: This analysis indicates that nebivolol appears to be a cost-effective treatment for elderly patients with heart failure compared with standard care.

Detection of Extracolonic Pathologic Findings with CT Colonography: A Discrete Choice Experiment of Perceived Benefits versus Harms

PURPOSE To determine the maximum rate of false-positive diagnoses that patients and health care professionals were willing to accept in exchange for detection of extracolonic malignancy by using computed tomographic (CT) colonography for colorectal cancer screening. MATERIALS AND METHODS After obtaining ethical approval and informed consent, 52 patients and 50 health care professionals undertook two discrete choice experiments where they chose between unrestricted CT colonography that examined intra- and extracolonic organs or CT colonography restricted to the colon, across different scenarios. The first experiment detected one extracolonic malignancy per 600 cases with a false-positive rate varying across scenarios from 0% to 99.8%. One experiment examined radiologic follow-up generated by false-positive diagnoses while the other examined invasive follow-up. Intracolonic performance was identical for both tests. The median tipping point (maximum acceptable false-positive rate for extracolonic findings) was calculated overall and for both groups by bootstrap analysis. RESULTS The median tipping point for radiologic follow-up occurred at a false-positive rate greater than 99.8% (interquartile ratio [IQR], 10 to >99.8%). Participants would tolerate at least a 99.8% rate of unnecessary radiologic tests to detect an additional extracolonic malignancy. The median tipping-point for invasive follow-up occurred at a false-positive rate of 10% (IQR, 2 to >99.8%). Tipping points were significantly higher for patients than for health care professionals for both experiments (>99.8 vs 40% for radiologic follow-up and >99.8 vs 5% for invasive follow-up, both P < .001). CONCLUSION Patients and health care professionals are willing to tolerate high rates of false-positive diagnoses with CT colonography in exchange for diagnosis of extracolonic malignancy. The actual specificity of screening CT colonography for extracolonic findings in clinical practice is likely to be highly acceptable to both patients and health care professionals. Online supplemental material is available for this article.

A cluster randomised controlled trial of an occupational therapy intervention for residents with stroke living in UK care homes (OTCH) : study protocol

BackgroundThe occupational therapy (OT) in care homes study (OTCH) aims to investigate the effect of a targeted course of individual OT (with task training, provision of adaptive equipment, minor environmental adaptations and staff education) for stroke survivors living in care homes, compared to usual care.Methods/DesignA cluster randomised controlled trial of United Kingdom (UK) care homes (n = 90) with residents (n = 900) who have suffered a stroke or transient ischaemic attack (TIA), and who are not receiving end-of-life care. Homes will be stratified by centre and by type of care provided and randomised (50:50) using computer generated blocked randomisation within strata to receive either the OT intervention (3 months intervention from an occupational therapist) or control (usual care). Staff training on facilitating independence and mobility and the use of adaptive equipment, will be delivered to every home, with control homes receiving this after the 12 month follow-up.Allocation will be concealed from the independent assessors, but the treating therapists, and residents will not be masked to the intervention. Measurements are taken at baseline prior to randomisation and at 3, 6 and 12 months post randomisation. The primary outcome measure is independence in self-care activities of daily living (Barthel Activities of Daily Living Index). Secondary outcome measures are mobility (Rivermead Mobility Index), mood (Geriatric Depression Scale), preference based quality of life measured from EQ-5D and costs associated with each intervention group. Quality adjusted life years (QALYs) will be derived based on the EQ-5D scores. Cost effectiveness analysis will be estimated and measured by incremental cost effectiveness ratio. Adverse events will be recorded.DiscussionThis study will be the largest cluster randomised controlled trial of OT in care homes to date and will clarify the currently inconclusive literature on the efficacy of OT for stroke and TIA survivors residing in care homes.Trial registrationISRCTN00757750

Patients' & Healthcare Professionals' Values Regarding True- & False-Positive Diagnosis when Colorectal Cancer Screening by CT Colonography: Discrete Choice Experiment

Purpose To establish the relative weighting given by patients and healthcare professionals to gains in diagnostic sensitivity versus loss of specificity when using CT colonography (CTC) for colorectal cancer screening. Materials and Methods Following ethical approval and informed consent, 75 patients and 50 healthcare professionals undertook a discrete choice experiment in which they chose between “standard” CTC and “enhanced” CTC that raised diagnostic sensitivity 10% for either cancer or polyps in exchange for varying levels of specificity. We established the relative increase in false-positive diagnoses participants traded for an increase in true-positive diagnoses. Results Data from 122 participants were analysed. There were 30 (25%) non-traders for the cancer scenario and 20 (16%) for the polyp scenario. For cancer, the 10% gain in sensitivity was traded up to a median 45% (IQR 25 to >85) drop in specificity, equating to 2250 (IQR 1250 to >4250) additional false-positives per additional true-positive cancer, at 0.2% prevalence. For polyps, the figure was 15% (IQR 7.5 to 55), equating to 6 (IQR 3 to 22) additional false-positives per additional true-positive polyp, at 25% prevalence. Tipping points were significantly higher for patients than professionals for both cancer (85 vs 25, p<0.001) and polyps (55 vs 15, p<0.001). Patients were willing to pay significantly more for increased sensitivity for cancer (p = 0.021). Conclusion When screening for colorectal cancer, patients and professionals believe gains in true-positive diagnoses are worth much more than the negative consequences of a corresponding rise in false-positives. Evaluation of screening tests should account for this.