Browsing by Author "Cook, Jonathan Alistair"

Now showing 1 - 20 of 24

64-slice computed tomography angiography in the diagnosis and assessment of coronary artery disease : systematic review and meta-analysis
(BMJ, 2008) Mowatt, Graham; Cook, Jonathan Alistair; Hillis, Graham Scott; Walker, Shonagh Mary; Fraser, Cynthia Mary; Jia, Xueli; Waugh, Norman Robert; University of Aberdeen, School of Medicine & Dentistry, Division of Applied Health Sciences
Objective To assess whether 64-slice computed tomography (CT) angiography might replace some coronary angiography (CA) for diagnosis and assessment of coronary artery disease (CAD). Methods We searched electronic databases, conference proceedings and scanned reference lists of included studies. Eligible studies compared 64-slice CT with a reference standard of CA in adults with suspected/known CAD, reporting sensitivity and specificity or true and false positives and negatives. Data were pooled using the hierarchical summary receiver operating characteristic model. Results Forty studies were included; 28 provided sufficient data for inclusion in the meta-analyses, all using a cutoff of ≥ 50% stenosis to define significant CAD. In patient-based detection (n=1286) 64-slice CT pooled sensitivity was 99% (95% credible interval (CrI) 97 to 99%), specificity 89% (95% CrI 83 to 94%), median positive predictive value (PPV) across studies 93% (range 64 to 100%) and negative predictive value (NPV) 100% (range 86 to 100%). In segment-based detection (n=14,199) 64-slice CT pooled sensitivity was 90% (95% CrI 85 to 94%), specificity 97% (95% CrI 95 to 98%), median positive predictive value (PPV) across studies 76% (range 44 to 93%) and negative predictive value (NPV) 99% (range 95 to 100%). Conclusions 64-slice CT is highly sensitive for patient-based detection of CAD and has high NPV. An ability to rule out significant CAD means that it may have a role in the assessment of chest pain, particularly when the diagnosis remains uncertain despite clinical evaluation and simple non-invasive testing.
Assessing methods to specify the target difference for a randomised controlled trial : DELTA (Difference ELicitation in TriAls) review
(2014-05-01) Cook, Jonathan Alistair; Hislop, Jennifer Margaret; Adewuyi, Temitope E; Harrild, Kirsten Ann; Altman, Douglas G; Ramsay, Craig R; Fraser, Cynthia; Buckley, Brian; Fayers, Peter; Harvey, Ian; Briggs, Andrew H; Norrie, John D; Fergusson, Dean; Ford, Ian; Vale, Luke David; University of Aberdeen.Other Applied Health Sciences; University of Aberdeen.Institute of Applied Health Sciences
The challenges faced in the design, conduct and analysis of surgical randomised controlled trials
(BMC, 2009-02-06) Cook, Jonathan Alistair; University of Aberdeen, School of Medicine & Dentistry, Division of Applied Health Sciences
Randomised evaluations of surgical interventions are rare; some interventions have been widely adopted without rigorous evaluation. Unlike other medical areas, the randomised controlled trial (RCT) design has not become the default study design for the evaluation of surgical interventions. Surgical trials are difficult to successfully undertake and pose particular practical and methodological challenges. However, RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use. This article will consider the design, conduct and analysis of an RCT of a surgical intervention. The issues will be reviewed under three headings: the timing of the evaluation, defining the research question and trial design issues. Recommendations on the conduct of future surgical RCTs are made. Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessmentof surgical interventions and enable the conduct of appropriate and well-designed trials.
The challenges faced in the design, conduct and analysis of surgical randomised trials
(BMC, 2009) Cook, Jonathan Alistair
Randomised evaluations of surgical interventions are rare; some interventions have been widely adopted without rigorous evaluation. Unlike other medical areas, the randomised controlled trial (RCT) design has not become the default study design for the evaluation of surgical interventions. Surgical trials are difficult to successfully undertake and pose particular practical and methodological challenges. However, RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use. This article will consider the design, conduct and analysis of an RCT of a surgical intervention. The issues will be reviewed under three headings: the timing of the evaluation, defining the research question and trial design issues. Recommendations on the conduct of future surgical RCTs are made. Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessment of surgical interventions and enable the conduct of appropriate and well-designed trials.
Challenges in evaluating surgical innovation
(Elsevier, 2009) Ergina, Patrick L; Cook, Jonathan Alistair; Blazeby, Jane M; Clavein, Pierre-Alain; Reeves, Barnaby C; Seiler, Christoph M; Boutron, Isabelle
Research on surgical interventions is associated with several methodological and practical challenges of which few, if any, apply only to surgery. However, surgical evaluation is especially demanding because many of these challenges coincide. In this report, the second of three on surgical innovation and evaluation, we discuss obstacles related to the study design of randomised controlled trials and non-randomised studies assessing surgical interventions. We also describe the issues related to the nature of surgical procedures—for example, their complexity, surgeon-related factors, and the range of outcomes. Although difficult, surgical evaluation is achievable and necessary. Solutions tailored to surgical research and a framework for generating evidence on which to base surgical practice are essential.
Clinical and cost-effectiveness of internal limiting membrane peeling for patients with idiopathic full thickness macular hole. Protocol for a Randomised Controlled Trial : FILMS (Full-thickness macular hole and Internal Limiting Membrane peeling Study)
(BMC, 2008-11-03) Lois, Noemi; Burr, Jennifer Margaret; Norrie, John David; Vale, Luke David; Cook, Jonathan Alistair; McDonald, Alison Mary; FILMS Group; University of Aberdeen, School of Medicine & Dentistry, Division of Applied Health Sciences
Background: A full-thickness macular hole (FTMH) is a common retinal condition associated with impaired vision. Randomised controlled trials (RCTs) have demonstrated that surgery, by means of pars plana vitrectomy and post-operative intraocular tamponade with gas, is effective for stage 2, 3 and 4 FTMH. Internal limiting membrane (ILM) peeling has been introduced as an additional surgical manoeuvre to increase the success of the surgery; i.e. increase rates of hole closure and visual improvement. However, little robust evidence exists supporting the superiority of ILM peeling compared with no-peeling techniques. The purpose of FILMS (Fullthickness macular hole and Internal Limiting Membrane peeling Study) is to determine whether ILM peeling improves the visual function, the anatomical closure of FTMH, and the quality of life of patients affected by this disorder, and the cost-effectiveness of the surgery. Methods/Design: Patients with stage 2–3 idiopathic FTMH of less or equal than 18 months duration (based on symptoms reported by the participant) and with a visual acuity ≤ 20/40 in the study eye will be enrolled in this FILMS from eight sites across the UK and Ireland. Participants will be randomised to receive combined cataract surgery (phacoemulsification and intraocular lens implantation) and pars plana vitrectomy with postoperative intraocular tamponade with gas, with or without ILM peeling. The primary outcome is distance visual acuity at 6 months. Secondary outcomes include distance visual acuity at 3 and 24 months, near visual acuity at 3, 6, and 24 months, contrast sensitivity at 6 months, reading speed at 6 months, anatomical closure of the macular hole at each time point (1, 3, 6, and 24 months), health related quality of life (HRQOL) at six months, costs to the health service and the participant, incremental costs per quality adjusted life year (QALY) and adverse events. Discussion: FILMS will provide high quality evidence on the role of ILM peeling in FTMH surgery. Trial registration: This trial is registered with Current Controlled Trials ISRCTN number 33175422 and Clinical Trials.gov identifier NCT00286507.
The clinical effectiveness and cost-effectiveness of screening for open angle glaucoma : a systematic review and economic evaluation
(Gray Publishing, 2007-10) Burr, Jennifer Margaret; Mowatt, Graham; Hernández, Rodolfo Andrés; Siddiqui, Muhammad Ardul Rehman; Cook, Jonathan Alistair; Lourenco, Tania; Ramsay, Craig R; Vale, Luke David; Fraser, Cynthia Mary; Azuara-Blanco, Augusto; Deeks, J.; Cairns, J.; Wormald, R.; McPherson, S.; Rabindranath, K.; Grant, Adrian Maxwell; University of Aberdeen, School of Medicine & Dentistry, Division of Applied Health Sciences
Objectives: To assess whether open angle glaucoma (OAG) screening meets the UK National Screening Committee criteria, to compare screening strategies with case finding, to estimate test parameters, to model estimates of cost and cost-effectiveness, and to identify areas for future research. Data sources: Major electronic databases were searched up to December 2005. Review methods: Screening strategies were developed by wide consultation. Markov submodels were developed to represent screening strategies. Parameter estimates were determined by systematic reviews of epidemiology, economic evaluations of screening, and effectiveness (test accuracy, screening and treatment). Tailored highly sensitive electronic searches were undertaken. Results: Most potential screening tests reviewed had an estimated specificity of 85% or higher. No test was clearly most accurate, with only a few, heterogeneous studies for each test. No randomised controlled trials (RCTs) of screening were identified. Based on two treatment RCTs, early treatment reduces the risk of progression. Extrapolating from this, and assuming accelerated progression with advancing disease severity, without treatment the mean time to blindness in at least one eye was approximately 23 years, compared to 35 years with treatment. Prevalence would have to be about 3–4% in 40 year olds with a screening interval of 10 years to approach costeffectiveness. It is predicted that screening might be cost-effective in a 50-year-old cohort at a prevalence of 4% with a 10-year screening interval. General population screening at any age, thus, appears not to be cost-effective. Selective screening of groups with higher prevalence (family history, black ethnicity) might be worthwhile, although this would only cover 6% of the population. Extension to include other at-risk cohorts (e.g. myopia and diabetes) would include 37% of the general population, but the prevalence is then too low for screening to be considered cost-effective. Screening using a test with initial automated classification followed by assessment by a specialised optometrist, for test positives, was more cost-effective than initial specialised optometric assessment. The cost-effectiveness of the screening programme was highly sensitive to the perspective on costs (NHS or societal). In the base-case model, the NHS costs of visual impairment were estimated as £669. If annual societal costs were £8800, then screening might be considered cost-effective for a 40-year-old cohort with 1% OAG prevalence assuming a willingness to pay of £30,000 per quality-adjusted life-year. Of lesser importance were changes to estimates of attendance for sight tests, incidence of OAG, rate of progression and utility values for each stage of OAG severity. Cost-effectiveness was not particularly sensitive to the accuracy of screening tests within the ranges observed. However, a highly specific test is required to reduce large numbers of false-positive referrals. The findings that population screening is unlikely to be cost-effective are based on an economic model whose parameter estimates have considerable uncertainty. In particular, if rate of progression and/or costs of visual impairment are higher than estimated then screening could be cost-effective. Conclusions: While population screening is not costeffective, the targeted screening of high-risk groups may be. Procedures for identifying those at risk, for quality assuring the programme, as well as adequate service provision for those screened positive would all be needed. Glaucoma detection can be improved by increasing attendance for eye examination, and improving the performance of current testing by either refining practice or adding in a technology-based first assessment, the latter being the more cost-effective option. This has implications for any future organisational changes in community eye-care services. Further research should aim to develop and provide quality data to populate the economic model, by conducting a feasibility study of interventions to improve detection, by obtaining further data on costs of blindness, risk of progression and health outcomes, and by conducting an RCT of interventions to improve the uptake of glaucoma testing.
A cost-utility analysis of multivitamin and multimineral supplements in men and women aged 65 years and over
(Elsevier, 2007) Kilonzo, Mary Mueni; Vale, Luke David; Cook, Jonathan Alistair; Milne, Anne Catherine; Stephen, Audrey Isabella; Avenell, Alison; MAVIS Trial Group; University of Aberdeen, School of Medicine & Dentistry, Division of Applied Health Sciences
Background and Aims As people age there is a progressive dysregulation of the immune system that may lead to an increased risk of infections, which may precipitate hospital admission in people with chronic heart or respiratory diseases. Mineral and vitamin supplementation in older people could therefore influence infections in older people. However, the evidence from the available randomised controlled trials is mixed. The aim of the study was to assess the relative efficiency of multivitamin and multimineral supplementation compared with no supplementation. Methods Cost-utility analysis alongside a randomised controlled trial. Participants aged 65 years or over from six general practices in Grampian, Scotland were studied. They were randomised to one tablet daily of either a multivitamin and multimineral supplement or matching placebo. Exclusion criteria were: use of mineral, vitamin or fish oil supplements in the previous three months (one month for water soluble vitamins), vitamin B12 injection in the last three months. Results Nine hundred and ten participants were recruited (454 placebo and 456 supplementation). Use of health service resources and costs were similar between the two groups. The supplementation arm was more costly although this was not statistically significant (£15 per person, 95% CI -3.75 to 34.95). After adjusting for minimisation and baseline EQ-5D scores supplementation was associated with fewer QALYs per person (–0.018, 95% CI -0.04 to 0.002). It was highly unlikely that supplementation would be considered cost-effective. Conclusions The evidence from this study suggests that it is highly unlikely that supplementation could be considered cost-effective.
The curious case of an internal pilot in a multicentre randomised trial-time for a rethink?
(2016-12-13) Cook, Jonathan Alistair; Beard, David John; Cook, Johanna Rosemary; MacLennan, Graeme Stewart; University of Aberdeen.Aberdeen Centre for Evaluation; University of Aberdeen.Institute of Applied Health Sciences
Effect of multivitamin and multimineral supplementation on cognitive function in men and women aged 65 years and over : a randomised controlled trial
(BMC, 2007-05-02) McNeil, Geraldine; Avenell, Alison; Campbell, Marion Kay; Cook, Jonathan Alistair; Hannaford, Philip Christopher; Kilonzo, Mary Mueni; Milne, Anne Catherine; Ramsay, Craig R; Seymour, David Gwyn; Stephen, Audrey Isabella; Vale, Luke David; MAVIS Trial Group; University of Aberdeen, School of Medicine & Dentistry, Division of Applied Health Sciences
Background: Observational studies have frequently reported an association between cognitive function and nutrition in later life but randomised trials of B vitamins and antioxidant supplements have mostly found no beneficial effect. We examined the effect of daily supplementation with 11 vitamins and 5 minerals on cognitive function in older adults to assess the possibility that this could help to prevent cognitive decline. Methods: The study was carried out as part of a randomised double blind placebo controlled trial of micronutrient supplementation based in six primary care health centres in North East Scotland. 910 men and women aged 65 years and over living in the community were recruited and randomised: 456 to active treatment and 454 to placebo. The active treatment consisted of a single tablet containing eleven vitamins and five minerals in amounts ranging from 50–210 % of the UK Reference Nutrient Intake or matching placebo tablet taken daily for 12 months. Digit span forward and verbal fluency tests, which assess immediate memory and executive functioning respectively, were conducted at the start and end of the intervention period. Risk of micronutrient deficiency at baseline was assessed by a simple risk questionnaire. Results: For digit span forward there was no evidence of an effect of supplements in all participants or in sub-groups defined by age or risk of deficiency. For verbal fluency there was no evidence of a beneficial effect in the whole study population but there was weak evidence for a beneficial effect of supplementation in the two pre-specified subgroups: in those aged 75 years and over (n 290; mean difference between supplemented and placebo groups 2.8 (95% CI -0.6, 6.2) units) and in those at increased risk of micronutrient deficiency assessed by the risk questionnaire (n 260; mean difference between supplemented and placebo groups 2.5 (95% CI -1.0, 6.1) units). Conclusion: The results provide no evidence for a beneficial effect of daily multivitamin and multimineral supplements on these domains of cognitive function in community-living people over 65 years. However, the possibility of beneficial effects in older people and those at greater risk of nutritional deficiency deserves further attention.
How surgical Trainee Research Collaboratives achieve success : a mixed methods study to develop trainee engagement strategies
(2023-12-10) Clement, Clare; Coulman, Karen; Heywood, Nick; Pinkney, Tom; Blazeby, Jane; Blencowe, Natalie S.; Cook, Jonathan Alistair; Bulbulia, Richard; Arenas-Pinto, Alejandro; Snowdon, Claire; Hilton, Zoe; Magill, Laura; MacLennan, Graeme; Glasbey, James; Nepogodiev, Dmitri; Hardy, Victoria; Lane, J. Athene; University of Aberdeen.Aberdeen Centre for Evaluation; University of Aberdeen.Centre for Healthcare Randomised Trials (CHaRT); University of Aberdeen.Institute of Applied Health Sciences
Outcomes of stenting after uncomplicated ureteroscopy: systematic review and meta-analysis.
(BMJ Publishing, 2007-03-17) Nabi, G; Cook, Jonathan Alistair; N'Dow, James Michael Olu; McClinton, S; Ureteral Calculi; University of Aberdeen, School of Medicine & Dentistry, Division of Applied Health Sciences
Objective To investigate the potential beneficial and adverse effects of routine ureteric stent placement after ureteroscopy. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Cochrane controlled trials register (2006 issue 2), Embase, and Medline (1966 to 31 March 2006), without language restrictions. Review methods We included all randomised controlled trials that reported various outcomes with or without stenting after ureteroscopy. Two reviewers independently extracted data and assessed quality. Meta-analyses used both fixed and random effects models with dichotomous data reported as relative risk and continuous data as a weighted mean difference with 95% confidence intervals. Results Nine randomised controlled trials (reporting 831 participants) were identified. The incidence of lower urinary tract symptoms was significantly higher in participants who had a stent inserted (relative risk 2.25, 95% confidence interval 1.14 to 4.43, for dysuria; 2.00, 1.11 to 3.62, for frequency or urgency) after ureteroscopy. There was no significant difference in postoperative requirement for analgesia, urinary tract infections, stone free rate, and ureteric strictures in the two groups. Because of marked heterogeneity, formal pooling of data was not possible for some outcomes such as flank pain. A pooled analysis showed a reduced likelihood of unplanned medical visits or admission to hospital in the group with stents (0.53, 0.17 to 1.60), although this difference was not significant. None of the trials reported on health related quality of life. Cost reported in three randomised controlled trials favoured the group without stents. The overall quality of trials was poor and reporting of outcomes inconsistent. Conclusions Patients with stents after ureteroscopy have significantly higher morbidity in the form of irritative lower urinary symptoms with no influence on stone free rate, rate of urinary tract infection, requirement for analgesia, or long term ureteric stricture formation. Because of the marked heterogeneity and poor quality of reporting of the included trials, the place of stenting in the managementof patients after uncomplicated ureteroscopy remains unclear.
A pragmatic multi-centre randomised controlled trial of fluid loading and level of dependency in high-risk surgical patients undergoing major elective surgery : trial protocol
(2010-04-16) Cuthbertson, Brian; Campbell, Marion Kay; Stott, S.a.; Vale, Luke David; Norrie, John David; Kinsella, John; Cook, Jonathan Alistair; Brittenden, Julie; Grant, Adrian Maxwell; Foccus Study Group; University of Aberdeen.Other Applied Health Sciences; University of Aberdeen.Applied Medicine; University of Aberdeen.Institute of Applied Health Sciences
Predicting death and readmission after intensive care discharge
(Oxford Journals, 2008-06) Campbell, Alison J.; Cook, Jonathan Alistair; Adey, Gillian; Cuthbertson, Brian; University of Aberdeen, School of Medicine & Dentistry, Division of Applied Health Sciences
Background: Despite initial recovery from critical illness, many patients deteriorate after discharge from the intensive care unit (ICU). We examined prospectively collected data in an attempt to identify patients at risk of readmission or death after intensive care discharge. Methods: This was a secondary analysis of clinical audit data from patients discharged alive from a mixed medical and surgical (non-cardiac) ICU. Results: Four hundred and seventy-five patients (11.2%) died in hospital after discharge from the ICU. Increasing age, time in hospital before intensive care admission, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and discharge Therapeutic Intervention Scoring System (TISS) score were independent risk factors for death after intensive care discharge. Three hundred and eighty-five patients (8.8%) were readmitted to intensive care during the same hospital admission. Increasing age, time in hospital before intensive care, APACHE II score, and discharge to a high dependency unit were independent risk factors for readmission. One hundred and forty-three patients (3.3%) were readmitted within 48 h of intensive care discharge. APACHE II scores and discharge to a high dependency or other ICU were independent risk factors for early readmission. The overall discriminant ability of our models was moderate with only marginal benefit over the APACHE II scores alone. Conclusions: We identified risk factors associated with death and readmission to intensive care. It was not possible to produce a definitive model based on these risk factors for predicting death or readmission in an individual patient.
Randomised controlled trial comparing rubber band ligation with stapled haemorrhoidopexy for Grade II circumferential haemorrhoids : Long-term results
(2010-06) Shanmugam, V.; Muthukumarasamy, G.; Cook, Jonathan Alistair; Vale, Luke David; Watson, Angus; Loudon, M. A.; University of Aberdeen.Other Applied Health Sciences
Randomised trial of glutamine and selenium supplemented parenteral nutrition for critically ill patients
(BioMed Central, 2007-09-20) Andrews, Peter J.D.; Avenell, Alison; Noble, David W.; Campbell, Marion Kay; Battison, Claire G.; Croal, Bernard L.; Simpson, William G.; Norrie, John David; Vale, Luke David; Cook, Jonathan Alistair; De Verteuil, Robyn; Milne, Anne Catherine; Trials Management Group; University of Aberdeen, School of Medicine & Dentistry, Division of Applied Health Sciences
Background: Mortality rates in the Intensive Care Unit and subsequent hospital mortality rates in the UK remain high. Infections in Intensive Care are associated with a 2–3 times increased risk of death. It is thought that under conditions of severe metabolic stress glutamine becomes "conditionally essential". Selenium is an essential trace element that has antioxidant and anti-inflammatory properties. Approximately 23% of patients in Intensive Care require parenteral nutrition and glutamine and selenium are either absent or present in low amounts. Both glutamine and selenium have the potential to influence the immune system through independent biochemical pathways. Systematic reviews suggest that supplementing parenteral nutrition in critical illness with glutamine or selenium may reduce infections and mortality. Pilot data has shown that more than 50% of participants developed infections, typically resistant organisms. We are powered to show definitively whether supplementation of PN with either glutamine or selenium is effective at reducing new infections in critically ill patients. Methods/design: 2 × 2 factorial, pragmatic, multicentre, double-blind, randomised controlled trial. The trial has an enrolment target of 500 patients. Inclusion criteria include: expected to be in critical care for at least 48 hours, aged 16 years or over, patients who require parenteral nutrition and are expected to have at least half their daily nutritional requirements given by that route. Allocation is to one of four iso-caloric, iso-nitrogenous groups: glutamine, selenium, both glutamine & selenium or no additional glutamine or selenium. Trial supplementation is given for up to seven days on the Intensive Care Unit and subsequent wards if practicable. The primary outcomes are episodes of infection in the 14 days after starting trial nutrition and mortality. Secondary outcomes include antibiotic usage, length of hospital stay, quality of life and cost-effectiveness. Discussion: To date more than 285 patients have been recruited to the trial from 10 sites in Scotland. Recruitment is due to finish in August 2008 with a further six months follow up. We expect to report the results of the trial in summer 2009. Trial registration: This trial is registered with the International Standard Randomised Controlled Trial Number system. ISRCTN87144826
Recruitment to publicly funded trials - are surgical trials really different?
(Elsevier, 2008-09) Cook, Jonathan Alistair; Ramsay, Craig R; Norrie, John David; University of Aberdeen, School of Medicine & Dentistry, Division of Applied Health Sciences
Good recruitment is integral to the conduct of a high-quality randomised controlled trial. It has been suggested that recruitment is particularly difficult for evaluations of surgical interventions, a field in which there is a dearth of evidence from randomised comparisons. While there is anecdotal speculation to support the inference that recruitment to surgical trials is more challenging than for medical trials we are unaware of any formal assessment of this. In this paper, we compare recruitment to surgical and medical trials using a cohort of publicly funded trials. Data: Overall recruitment to trials was assessed using of a cohort of publicly funded trials (n = 114). Comparisons were made by using the Recruitment Index, a simple measure of recruitment activity for multicentre randomised controlled trials. Recruitment at the centre level was also investigated through three example surgical trials. Results: The Recruitment Index was found to be higher, though not statistically significantly, in the surgical group (n = 18, median = 38.0 IQR (10.7, 77.4)) versus (n = 81, median = 34.8 IQR (11.7, 98.0)) days per recruit for the medical group (median difference 1.7 (− 19.2, 25.1); p = 0.828). For the trials where the comparison was between a surgical and a medical intervention, the Recruitment Index was substantially higher (n = 6, 68.3 (23.5, 294.8)) versus (n = 93, 34.6 (11.7, 90.0); median difference 25.9 (− 35.5, 221.8); p = 0.291) for the other trials. Conclusions: There was no clear evidence that surgical trials differ from medical trials in terms of recruitment activity. There was, however, support for the inference that medical versus surgical trials are more difficult to recruit to. Formal exploration of the recruitment data through a modelling approach may go some way to tease out where important differences exist.
Screening tests for detecting open angle glaucoma : systematic review and meta-analysis
(The Association for Research in Vision and Ophthalmology, Inc., 2008-07-09) Mowatt, Graham; Burr, Jennifer Margaret; Cook, Jonathan Alistair; Siddiqui, M. A. Rehman; Ramsay, Craig R; Fraser, Cynthia Mary; Azuara-Blanco, Augusto; Deeks, Jonathan J
PURPOSE. To assess the comparative accuracy of potential screening tests for open angle glaucoma (OAG). METHODS. Medline, Embase, Biosis (to November 2005), Science Citation Index (to December 2005), and The Cochrane Library (Issue 4, 2005) were searched. Studies assessing candidate screening tests for detecting OAG in persons older than 40 years that reported true and false positives and negatives were included. Meta-analysis was undertaken using the hierarchical summary receiver operating characteristic model. RESULTS. Forty studies enrolling over 48,000 people reported nine tests. Most tests were reported by only a few studies. Frequency-doubling technology (FDT; C-20-1) was significantly more sensitive than ophthalmoscopy (30, 95% credible interval [CrI] 0–62) and Goldmann applanation tonometry (GAT; 45, 95% CrI 17–68), whereas threshold standard automated perimetry (SAP) and Heidelberg Retinal Tomograph (HRT II) were both more sensitive than GAT (41, 95% CrI 14–64 and 39, 95% CrI 3–64, respectively). GAT was more specific than both FDT C-20-5 (19, 95% CrI 0-53) and threshold SAP (14, 95% CrI 1-37). Judging performance by diagnostic odds ratio, FDT, oculokinetic perimetry, and HRT II are promising tests. Ophthalmoscopy, SAP, retinal photography, and GAT had relatively poor performance as single tests. These findings are based on heterogeneous data of limited quality and as such are associated with considerable uncertainty. CONCLUSIONS. No test or group of tests was clearly superior for glaucoma screening. Further research is needed to evaluate the comparative accuracy of the most promising tests.
Systematic review of the agreement of tonometers with goldmann applanation tonometry
(2012-08) Cook, Jonathan Alistair; Botello Pinzon, Adriana Paolo; Elders, Andrew; Fathi Ali, Alia; Azuara-Blanco, Augusto; Fraser, Cynthia; McCormack, Kirsty; Margaret Burr, Jennifer; Surveillance of Ocular Hypertension Study Group; University of Aberdeen.Other Applied Health Sciences
Systematic review of the clinical effectiveness and cost-effectiveness of 64-slice or higher computed tomography angiography as an alternative to invasive coronary angiography in the investigation of coronary artery disease
(Gray Publishing, 2008-05) Mowatt, Graham; Cummins, E.; Waugh, N.; Walker, S.; Cook, Jonathan Alistair; Jia, Xueli; Hillis, Graham S.; Fraser, Cynthia Mary
Objectives: To assess the clinical effectiveness and cost-effectiveness, in different patient groups, of the use of 64-slice or higher computed tomography (CT) angiography, instead of invasive coronary angiography (CA), for diagnosing people with suspected coronary artery disease (CAD) and assessing people with known CAD. Data sources: Electronic databases were searched from 2002 to December 2006. Review methods: Included studies were tabulated and sensitivity, specificity, positive and negative predictive values calculated. Meta-analysis models were fitted using hierarchical summary receiver operating characteristic curves. Summary sensitivity, specificity, positive and negative likelihood ratios and diagnostic odds ratios for each model were reported as a median and 95% credible interval (CrI). Searches were also carried out for studies on the cost-effectiveness of 64-slice CT in the assessment of CAD. Results: The diagnostic accuracy and prognostic studies enrolled over 2500 and 1700 people, respectively. The overall quality of the studies was reasonably good. In the pooled estimates, 64-slice CT angiography was highly sensitive (99%, 95% CrI 97 to 99%) for patientbased detection of significant CAD (defined as 50% or more stenosis), while across studies the negative predictive value (NPV) was very high (median 100%, range 86 to 100%). In segment-level analysis compared with patient-based detection, sensitivity was lower (90%, 95% CrI 85 to 94%, versus 99%, 95% CrI 97 to 99%) and specificity higher (97%, 95% CrI 95 to 98%, versus 89%, 95% CrI 83 to 94%), while across studies the median NPV was similar (99%, range 95 to 100%, versus 100%, range 86 to 100%). At individual coronary artery level the pooled estimates for sensitivity ranged from 85% for the left circumflex (LCX) artery to 95% for the left main artery, specificity ranged from 96% for both the left anterior descending (LAD) artery and LCX to 100% for the left main artery, while across studies the positive predictive value (PPV) ranged from 81% for the LCX to 100% for the left main artery and NPV was very high, ranging from 98% for the LAD (range 95 to 100%), LCX (range 93 to 100%) and right coronary artery (RCA) (range 94 to 100%) to 100% for the left main artery. The pooled estimates for bypass graft analysis were 99% (95% CrI 95 to 100%) sensitivity, 96% (95% CrI 86 to 99%) specificity, with median PPV and NPV values across studies of 93% (range 90 to 95%) and 99% (range 98 to 100%), respectively. This compares with, for stent analysis, a pooled sensitivity of 89% (95% CrI 68 to 97%), specificity 94% (95% CrI 83 to 98%), and median PPV and NPV values across studies of 77% (range 33 to 100%) and 96% (range 71 to 100%), respectively. Sixty-four-slice CT is almost as good as invasive CA in terms of detecting true positives. However, it is somewhat poorer in its rate of false positives. It seems likely that diagnostic strategies involving 64-slice CT will still require invasive CA for CT test positives, partly to identify CT false positives, but also because CA provides other information that CT currently does not, notably details of insertion site and distal run-off for possible coronary artery bypass graft (CABG). The high sensitivity of 64-slice CT avoids the costs of unnecessary CA in those referred for investigation but who do not have CAD. Given the possible, although small, associated death rate, avoiding these unnecessary CAs through the use of 64-slice CT may also confer a small immediate survival advantage. This in itself may be sufficient to outweigh the very marginally inferior rates of detection of true positives by strategies involving 64-slice CT. The avoidance of unnecessary CA through the use of 64-slice CT also appears likely to result in overall cost savings in the diagnostic pathway. Only if both the cost of CA is relatively low and the prevalence of CAD in the presenting population is relatively high (so that most patients will go on to CA) will the use of 64-slice CT be likely to result in a higher overall diagnostic cost per patient. Conclusions: The main value of 64-slice CT may at present be to rule out significant CAD. It is unlikely to replace CA in assessment for revascularisation of patients, particularly as angiography and angioplasty are often done on the same occasion. Further research is needed into the marginal advantages and costs of 256-slice machines compared with 64-sliceCT, the usefulness of 64-slice CT in people with suspected acute coronary syndrome, the potential of multislice computed tomography to examine plaque morphology, the role of CT in identifying patients suitable for CABG, and the concerns raised about repetitive use, or use of 64-slice or higher CT angiography in younger individuals or women of childbearing age.