Optical coherence tomography for the monitoring of neovascular age-related macular degeneration: a systematic review.

TOPIC: To compare the accuracy of optical coherence tomography (OCT) with alternative tests for monitoring neovascular age-related macular degeneration (nAMD) and detecting disease activity among eyes previously treated for this condition. CLINICAL RELEVANCE: Traditionally, fundus fluorescein angiography (FFA) has been considered the reference standard to detect nAMD activity, but FFA is costly and invasive. Replacement of FFA by OCT can be justified if there is a substantial agreement between tests. METHODS: Systematic review and meta-analysis. The index test was OCT. The comparator tests were visual acuity, clinical evaluation (slit lamp), Amsler chart, color fundus photographs, infrared reflectance, red-free images and blue reflectance, fundus autofluorescence imaging, indocyanine green angiography (ICGA), preferential hyperacuity perimetry, and microperimetry. We searched the following databases: MEDLINE, MEDLINE In-Process, EMBASE, Biosis, Science Citation Index, the Cochrane Library, Database of Abstracts of Reviews of Effects, MEDION, and the Health Technology Assessment database. The last literature search was conducted in March 2013. We used the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) to assess risk of bias. RESULTS: We included 8 studies involving more than 400 participants. Seven reported the performance of OCT (3 time-domain [TD] OCT, 3 spectral-domain [SD] OCT, 1 both types) and 1 reported the performance of ICGA in the detection of nAMD activity. We did not find studies directly comparing tests in the same population. The pooled sensitivity and specificity of TD OCT and SD OCT for detecting active nAMD was 85% (95% confidence interval [CI], 72%-93%) and 48% (95% CI, 30%-67%), respectively. One study reported ICGA with sensitivity of 75.9% and specificity of 88.0% for the detection of active nAMD. Half of the studies were considered to have a high risk of bias. CONCLUSIONS: There is substantial disagreement between OCT and FFA findings in detecting active disease in patients with nAMD who are being monitored. Both methods may be needed to monitor patients comprehensively with nAMD.

Optical coherence tomography for the diagnosis, monitoring and guiding of treatment for neovascular age-related macular degeneration: a systematic review and economic evaluation.

BACKGROUND: Age-related macular degeneration is the most common cause of sight impairment in the UK. In neovascular age-related macular degeneration (nAMD), vision worsens rapidly (over weeks) due to abnormal blood vessels developing that leak fluid and blood at the macula. OBJECTIVES: To determine the optimal role of optical coherence tomography (OCT) in diagnosing people newly presenting with suspected nAMD and monitoring those previously diagnosed with the disease. DATA SOURCES: Databases searched: MEDLINE (1946 to March 2013), MEDLINE In-Process & Other Non-Indexed Citations (March 2013), EMBASE (1988 to March 2013), Biosciences Information Service (1995 to March 2013), Science Citation Index (1995 to March 2013), The Cochrane Library (Issue 2 2013), Database of Abstracts of Reviews of Effects (inception to March 2013), Medion (inception to March 2013), Health Technology Assessment database (inception to March 2013). REVIEW METHODS: Types of studies: direct/indirect studies reporting diagnostic outcomes. INDEX TEST: time domain optical coherence tomography (TD-OCT) or spectral domain optical coherence tomography (SD-OCT). COMPARATORS: clinical evaluation, visual acuity, Amsler grid, colour fundus photographs, infrared reflectance, red-free images/blue reflectance, fundus autofluorescence imaging, indocyanine green angiography, preferential hyperacuity perimetry, microperimetry. Reference standard: fundus fluorescein angiography (FFA). Risk of bias was assessed using quality assessment of diagnostic accuracy studies, version 2. Meta-analysis models were fitted using hierarchical summary receiver operating characteristic curves. A Markov model was developed (65-year-old cohort, nAMD prevalence 70%), with nine strategies for diagnosis and/or monitoring, and cost-utility analysis conducted. NHS and Personal Social Services perspective was adopted. Costs (2011/12 prices) and quality-adjusted life-years (QALYs) were discounted (3.5%). Deterministic and probabilistic sensitivity analyses were performed. RESULTS: In pooled estimates of diagnostic studies (all TD-OCT), sensitivity and specificity [95% confidence interval (CI)] was 88% (46% to 98%) and 78% (64% to 88%) respectively. For monitoring, the pooled sensitivity and specificity (95% CI) was 85% (72% to 93%) and 48% (30% to 67%) respectively. The FFA for diagnosis and nurse-technician-led monitoring strategy had the lowest cost (£ 39,769; QALYs 10.473) and dominated all others except FFA for diagnosis and ophthalmologist-led monitoring (£ 44,649; QALYs 10.575; incremental cost-effectiveness ratio £ 47,768). The least costly strategy had a 46.4% probability of being cost-effective at £ 30,000 willingness-to-pay threshold. LIMITATIONS: Very few studies provided sufficient information for inclusion in meta-analyses. Only a few studies reported other tests; for some tests no studies were identified. The modelling was hampered by a lack of data on the diagnostic accuracy of strategies involving several tests. CONCLUSIONS: Based on a small body of evidence of variable quality, OCT had high sensitivity and moderate specificity for diagnosis, and relatively high sensitivity but low specificity for monitoring. Strategies involving OCT alone for diagnosis and/or monitoring were unlikely to be cost-effective. Further research is required on (i) the performance of SD-OCT compared with FFA, especially for monitoring but also for diagnosis; (ii) the performance of strategies involving combinations/sequences of tests, for diagnosis and monitoring; (iii) the likelihood of active and inactive nAMD becoming inactive or active respectively; and (iv) assessment of treatment-associated utility weights (e.g. decrements), through a preference-based study. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012001930. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Practicalities of using a modified version of the Cochrane Collaboration risk of bias tool for randomised and non-randomised study designs applied in a health technology assessment setting.

UNLABELLED: We describe our experience of using a modified version of the Cochrane risk of bias (RoB) tool for randomised and non-randomised comparative studies. OBJECTIVES: To assess time to complete RoB assessment. To assess inter-rater agreement. To explore the association between RoB and treatment effect size METHODS: Cochrane risk of bias assessment was performed on a sample of full text primary reports included in a systematic review comparing operative techniques for radical prostatectomy. Inter-rater agreement was assessed using the kappa statistic. RESULTS: Twenty-four studies were judged as high overall RoB, 13 were judged as low RoB and 11 were unclear. The weighted Kappa value was 0.35 indicating fair agreement. The median (range) time taken to rate each study was 30 min (10-49). The effect estimate for all studies was 0.61 (95% credible interval (CrI) 0.46-0.83) and 0.73 (95% CrI 0.29-1.75) for low risk studies. CONCLUSIONS: Although the process was time consuming, using a modified version of the RoB tool proved useful for demonstrating conservative effect estimates. That we only achieved a fair agreement between reviewers demonstrates the urgent need for further validation to improve inter-rater agreement. We suggest additional RoB levels could improve inter-rater reliability.

Management of the open abdomen: a national study of clinical outcome and safety of negative pressure wound therapy.

OBJECTIVE: To determine clinical outcome of open abdomen therapy and assess the influence of negative pressure wound therapy on outcome. BACKGROUND: Leaving the abdomen open (laparostomy) is an option following laparotomy for severe abdominal sepsis or trauma. Negative pressure wound therapy (NPWT) has become a popular means of managing laparostomy wounds. It may facilitate nursing care and delayed primary wound closure but the evidence to support its use is poor and concern has arisen about the risk of intestinal fistulation from exposed bowel, leading to an increased risk of death. METHODS: Prospective observational study of 578 patients treated with an open abdomen in 105 hospitals in the United Kingdom between January 1, 2010, and June 30, 2011. Propensity analysis was used to compare adverse outcomes (fistulation, death, intestinal failure, bleeding requiring intervention) and delayed primary closure rates in patients who did and did not receive NPWT. FINDINGS: The most common indication for an open abdomen (n = 398, 68.9%) was abdominal sepsis. Overall hospital mortality was 28.2%. The majority of patients (n = 355, 61.4%) were treated with NPWT. Intestinal fistulation [relative risk (RR) = 0.83, 95% confidence interval (CI): 0.44-1.58], death (RR = 0.87, 95% CI: 0.64-1.20), bleeding (RR = 0.74, 95% CI: 0.45-1.23), and intestinal failure (RR = 1.00, 95% CI: 0.64-1.57) were no more common in patients receiving NPWT, but the rate of delayed primary closure was significantly lower (RR = 0.74, 95% CI: 0.60-0.90, P = 0.002) when NPWT was used. CONCLUSIONS: The indications for an open abdomen in the United Kingdom appear to be significantly different to those described in N. America, where its use in the management of trauma predominates. NPWT in patients with an open abdomen is not associated with an increase in mortality or intestinal fistulation. It is, however, associated with a reduced rate of delayed primary closure. Although this may be related to patient selection, NPWT may leave patients with abdominal wall defects that require further treatment.

Pazopanib for the first-line treatment of patients with advanced and/or metastatic renal cell carcinoma : a NICE single technology appraisal.

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of pazopanib hydrochloride (GlaxoSmithKline) to submit evidence of the clinical and cost effectiveness of the drug for the first-line treatment of advanced and/or metastatic renal cell carcinoma, as part of the Institute's single technology appraisal (STA) process. The Aberdeen Health Technology Assessment Group were commissioned to act as the Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and NICE's subsequent decisions. The objective of this paper is to summarize the independent review and critique of the evidence submitted for the consideration of the NICE Appraisal Committee and NICE's subsequently issued guidance. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the manufacturer's submission to NICE. The ERG also independently searched for relevant evidence and modified the manufacturer's decision analytic model to examine the impact of altering some of the key assumptions. For progression-free survival (PFS), there was a statistically significant longer survival for pazopanib compared with placebo (as assessed by the ERG, based upon the original manufacturer submission with a clinical cut-off date of 23 May 2008) [median 11.1 vs. 2.8 months; hazard ratio (HR) 0.40; 95 % CI 0.27, 0.60]. Data from the indirect comparison suggested that pazopanib had a greater survival than interferon alpha (IFN-α) [HR 0.512; 95 % CI 0.326, 0.802] but provided no evidence of any difference compared with sunitinib (HR 0.949; 95 % CI 0.575, 1.568). With regard to overall survival, 64 % (n = 99) of patients in the pazopanib arm and 63 % (n = 49) of patients in the placebo arm had died and a total of 51 % (n = 40) of placebo patients had crossed over to receive pazopanib. Although data were provided on an intention-to-treat basis, crossover between therapies made such data difficult to interpret. There was no evidence of any statistically significant difference between pazopanib and best supportive care (HR 0.501; 95 % CI 0.136, 2.348). In the indirect comparison, there were no statistically significant differences between pazopanib and IFN-α (HR 0.627; 95 % CI 0.173, 2.269) or between pazopanib and sunitinib (HR 0.969; 95 % CI 0.359, 2.608). Based upon the work presented including a 12.5 % discount for pazopanib, sunitinib was extendedly dominated by a combination of pazopanib and IFN-α. As a consequence, the incremental cost per QALY for pazopanib versus IFN-α was £38,925. The results were not greatly altered over the range of univariate deterministic sensitivity analyses conducted by the manufacturer but pair-wise probabilistic sensitivity analyses suggested that given a threshold value of £30,000, there is a 54 % probability that pazopanib was preferred to sunitinib, 40 % chance against IFN-α and 47 % chance against best supportive care. The Appraisal Committee concluded that pazopanib should be recommended as a first-line treatment option for people with advanced renal cell carcinoma who have not received prior cytokine therapy and have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and if the manufacturer provides pazopanib with a 12.5 % discount on the list price and provides a possible future rebate linked to the outcome of the head-to-head COMPARZ trial, as agreed under the terms of the patient access scheme and to be confirmed when the COMPARZ trial data are made available.

Denosumab for treatment of bone metastases secondary to solid tumours: systematic review and network meta-analysis.

AIM: To evaluate the evidence for denosumab for the treatment of bone metastases secondary to solid tumours and, using a network meta-analysis, indirectly compare denosumab with bisphosphonates and best supportive care. DATA SOURCES: MEDLINE (1948 to April 2011), EMBASE (1980 to March 2011), Cochrane Library (all sections) (issue 1, 2011) and Web of Science with Conference Proceedings (1970 to May 2011) and additional meeting abstracts (2010 and 2011) were searched. STUDY ELIGIBILITY, PARTICIPANTS AND INTERVENTIONS: Only randomised controlled trials assessing denosumab, bisphosphonates or best supportive care in patients with bone metastases from any solid tumour were included. SYNTHESIS: Direct evidence comparing denosumab and zoledronic acid was assessed for breast cancer, prostate cancer and other solid tumours. Denosumab was compared with pamidronate and best supportive care through a network meta-analysis for each tumour type. The primary outcomes were time to first skeletal related event (SRE) and time to first and subsequent SRE. Secondary outcomes were skeletal morbidity rate, pain, quality of life (QoL) and overall survival. RESULTS: Denosumab was found to be more effective in delaying the time to first SRE and reducing the risk of first and subsequent SRE compared to zoledronic acid, placebo and pamidronate. In breast and prostate cancer, denosumab was effective in reducing skeletal morbidity rate compared with placebo. The lack of published data on pain and QoL meant that firm conclusions could not be made. Denosumab did not appear to have an affect on overall survival. LIMITATIONS: Network meta-analyses are subject to uncertainties and potential biases. CONCLUSIONS: Denosumab is effective in preventing SRE, but the effect on pain and QoL is unclear.

Assessing pharmacological interventions for bone metastases: the need for more patient-centered outcomes.

Bone metastases are associated with a broad spectrum of clinical sequelae. Pain, reduced mobility, skeletal complications and treatment-related events reduce quality of life. Numerous randomized controlled trials have evaluated pharmacological interventions to treat bone metastases. The primary outcomes used have evolved over the past 25 years; from improvement in pain to time to first skeletal-related event (SRE). In the current definition, a SRE consists of pathological fracture, spinal cord compression or the need for radiotherapy or surgery to the bone. Currently used outcomes can detect small differences between interventions. However, there are several limitations to SRE-related outcomes. In this article we illustrate the evolution of outcomes used in randomized controlled trials, critically appraising current outcomes used and proposing that more patient-centered outcomes are needed.

Eltrombopag for the treatment of chronic immune or idiopathic thrombocytopenic purpura: a NICE single technology appraisal.

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of eltrombopag (GlaxoSmithKline) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of patients with chronic immune or idiopathic thrombocytopenic purpura (ITP), as part of the their Single Technology Appraisal (STA) process. The Aberdeen Technology Assessment Review (TAR) Group, commissioned to act as the evidence review group (ERG), critically reviewed and supplemented the submitted evidence. This paper describes the company submission, the ERG review and NICE's subsequent decisions. The ERG critically appraised the clinical and cost-effectiveness evidence submitted by the manufacturer, independently searched for relevant literature, conducted a critical appraisal of the submitted economic models and explored the impact of altering some of the key model assumptions as well as combining relevant sensitivity analyses. Three trials were used to inform the safety and efficacy aspects of this submission; however, one high-quality randomized controlled trial (RAISE study) was the principal source of evidence and was used to inform the economic model. Eltrombopag had greater odds of achieving the primary outcome of a platelet count between 50 × 10^9/L and 400 × 10^9/L during the 6-month treatment period than placebo (odds ratio [OR] 8.2, 99% CI 3.6, 18.7). In the eltrombopag group, 50/83 (60%) of non-splenectomized patients and 18/49 (37%) of splenectomized patients achieved this outcome. The median duration of response was 10.9 weeks for eltrombopag (splenectomized 6 and non-splenectomized 13.4) compared with 0 for placebo. Eltrombopag patients required less rescue medication and had lower odds of bleeding events for both the splenectomized and the non-splenectomized patients. For a watch-and-rescue strategy of care, the comparator was placebo and the ERG found that substantial reductions in the cost of eltrombopag are needed before the incremental cost per QALY is less than £30,000. There was significant uncertainty, with the incremental cost-effectiveness ratio (ICER) reported varying from £33,561 to £103,500 per QALY (splenectomized) and £39,657 to £150,245 per QALY (non-splenectomized). All costs are presented in £, year 2008 values, as this was the costing year for the manufacturer's model. Other than bleeding, no adverse events were modelled. In relation to the long-term treatment model, the ERG questioned the robustness of the use of non-randomized non-comparative data. The base-case results restricting the time horizon to 2 years and prescribing eltrombopag as second-line treatment post-rituximab were found to be favourable towards eltrombopag. As rituximab is not a licensed treatment for ITP, the ERG were concerned that its inclusion may not be reflective of clinical practice. None of the treatment sequences resulted in an ICER approaching the recommended threshold of £30,000 per QALY gained. Eltrombopag appears to be a safe treatment for ITP (although long-term follow-up studies are awaited) and has short-term efficacy. However, NICE found based on the evidence submitted and reviewed that there was no robust evidence on the long-term efficacy or cost effectiveness of eltrombopag and a lack of direct evidence for eltrombopag tested against other relevant comparators.

Systematic review of escalated imatinib doses compared with sunitinib or best supportive care, for the treatment of people with unresectable/metastatic gastrointestinal stromal tumours whose disease has progressed on the standard imatinib dose.

INTRODUCTION: We conducted a systematic review of evidence on the effectiveness of imatinib at escalated doses of 600 mg/day or 800 mg/day for treatment of adults with unresectable or metastatic gastrointestinal stromal tumours (GIST), following progression on imatinib at the 400 mg/day dose, compared with sunitinib and/or 'best supportive care'. METHODS: Electronic searches were undertaken to identify relevant randomised controlled trials (RCTs), non-randomised studies, and case series reporting outcome data on survival, quality of life or adverse events. Titles and abstracts were screened by two reviewers and full text reports of potentially relevant studies assessed for inclusion. Included studies were quality assessed by two reviewers and data were extracted. Five studies reported data on the relevant population and were included. RESULTS AND DISCUSSION: Median overall survival for imatinib (800 mg/day) and sunitinib both were less than 2 years. Around 25% of patients required either an imatinib dose delay or reduction. Approximately one-third of patients receiving dose escalated imatinib (either dose) showed either response or stable disease. Amongst those responding to the escalated 800 mg/day dose, median progression-free survival was over 25 months. The statistical likelihood of response may depend on exon mutational status. There were few data and those that were available were potentially biased, due to their non-randomised nature. Further data are needed to justify international guideline recommendations on imatinib dose escalation. CONCLUSION: A prospective audit of management and outcomes for unresectable GIST patients treated with dose escalation upon progression at 400 mg/day may be appropriate as an RCT may be unfeasible.

Surveillance mammography for detecting ipsilateral breast tumour recurrence and metachronous contralateral breast cancer: a systematic review.

OBJECTIVES: To determine the diagnostic accuracy of surveillance mammography for detecting ipsilateral breast tumour recurrence and metachronous contralateral breast cancer in women previously treated for primary breast cancer. METHODS: A systematic review of surveillance mammography compared with ultrasound, magnetic resonance imaging (MRI), specialist-led clinical examination or unstructured primary care follow-up, using histopathological assessment for test positives and follow-up for test negatives as the reference standard. RESULTS: Nine studies met our inclusion criteria. Variations in study comparisons precluded meta-analysis. For routine ipsilateral breast tumour detection, surveillance mammography sensitivity ranged from 64-67% and specificity ranged from 85-97%. For MRI, sensitivity ranged from 86-100% and specificity was 93%. For non-routine ipsilateral breast tumour detection, sensitivity and specificity for surveillance mammography ranged from 50-83% and 57-75% and for MRI 93-100% and 88-96%. For routine metachronous contralateral breast cancer detection, one study reported sensitivity of 67% and specificity of 50% for both surveillance mammography and MRI. CONCLUSION: Although mammography is associated with high sensitivity and specificity, MRI is the most accurate test for detecting ipsilateral breast tumour recurrence and metachronous contralateral breast cancer in women previously treated for primary breast cancer. Results should be interpreted with caution because of the limited evidence base. Key Points • Surveillance mammography is associated with high sensitivity and specificity • Findings suggest that MRI is the most accurate test for detecting further breast cancer • Robust conclusions cannot be made due to the limited evidence base • Further research comparing surveillance mammography and other diagnostic tests is required.

Photodynamic diagnosis of bladder cancer compared with white light cystoscopy: Systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to assess the test performance and clinical effectiveness of photodynamic diagnosis (PDD) compared with white light cystoscopy (WLC) in people suspected of new or recurrent bladder cancer. METHODS: A systematic review was conducted of randomized controlled trials (RCTs), nonrandomized comparative studies, or diagnostic cross-sectional studies comparing PDD with WLC. Fifteen electronic databases and Web sites were searched (last searches April 2008). For clinical effectiveness, only RCTs were considered. RESULTS: Twenty-seven studies (2,949 participants) assessed test performance. PDD had higher sensitivity than WLC (92 percent, 95 percent confidence interval [CI], 80-100 percent versus 71 percent, 95 percent CI, 49-93 percent) but lower specificity (57 percent, 95 percent CI, 36-79 percent versus 72 percent, 95 percent CI, 47-96 percent). For detecting higher risk tumors, median range sensitivity of PDD (89 percent [6-100 percent]) was higher than WLC (56 percent [0-100 percent]) whereas for lower risk tumors it was broadly similar (92 percent [20-95 percent] versus 95 percent [8-100 percent]). Four RCTs (709 participants) using 5-aminolaevulinic acid (5-ALA) as the photosensitising agent reported clinical effectiveness. Using PDD at transurethral resection of bladder tumor (TURBT) resulted in fewer residual tumors at check cystoscopy (relative risk [RR], 0.37, 95 percent CI, 0.20-0.69) and longer recurrence-free survival (RR, 1.37, 95 percent CI, 1.18-1.59), compared with WLC. CONCLUSIONS: PDD detects more bladder tumors than WLC, including more high-risk tumors. Based on four RCTs reporting clinical effectiveness, 5-aminolaevulinic acid-mediated PDD at TURBT facilitates a more complete resection and prolongs recurrence-free survival.

A further use for the Harvest plot: a novel method for the presentation of data synthesis.

When performing a systematic review, whether or not a meta-analysis is performed, graphical displays can be useful. Data do still need to be described, ideally in graphical form. The Harvest plot has been developed to display combined data from several studies that allows demonstration of not only effect but also study quality. We describe a modification to the Harvest plot that allows the presentation of data that normally could not be included in a forest plot meta-analysis and allows extra information to be displayed. Using specific examples, we describe how the arrangement of studies, height of the bars and additional information can be used to enhance the plot. This is an important development, which by fulfilling Tufte's nine requirements for graphical presentation, allows researchers to display evidence in a flexible way. This means readers can follow an argument in a clear and efficient manner without the need for large volumes of descriptive text. Copyright © 2011 John Wiley & Sons, Ltd.

Systematic review of the efficacy and safety of using mesh in surgery for uterine or vaginal vault prolapse.

INTRODUCTION AND HYPOTHESIS: The aim of this study is to estimate efficacy and safety of mesh in surgery for uterine or vault prolapse. METHODS: Seventeen electronic databases were searched for relevant studies that were published from 1980 onwards. RESULTS: Fifty-four studies involving 7,054 women were included. For sacrocolpopexy (average follow-up 23 months), the risk of clinical recurrence ranged from 0% to 6%, persistent symptoms ranged from 3% to 31% and mesh erosion from 0% to 12%. For infracoccygeal sacropexy (average follow-up 13 months), the risk of clinical recurrence ranged from 0% to 25%, persistent symptoms from 2% to 21% and mesh erosion 0% to 21%. Limited evidence was available for sacrocolpoperineopexy and uterine suspension sling to draw reliable estimates. CONCLUSIONS: Sacrocolpopexy was associated with a low risk of recurrence but with a relatively high risk of mesh erosion. Ranges of estimates for outcomes for other mesh techniques were wide.

Screening tests for detecting open-angle glaucoma: systematic review and meta-analysis.

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 prognostic effectiveness of SPECT myocardial perfusion scintigraphy in patients with suspected or known coronary artery disease and following myocardial infarction.

OBJECTIVES: In patients with suspected or known coronary artery disease (CAD), or following myocardial infarction (MI), assessing the degree of ischaemia is important from a prognostic and therapeutic point of view. Single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy (MPS) is a non-invasive technique that allows the presence, location and extent of ischaemia to be determined. The aim of this systematic review was to assess the prognostic effectiveness of SPECT MPS. METHODS: We sought prognostic studies involving SPECT, exercise tolerance testing (ETT) and/or coronary angiography (CA) in people with suspected or known CAD, or following MI. Outcomes included cardiac death, non-fatal MI and revascularization. We searched the following databases: MEDLINE, PREMEDLINE, EMBASE, BIOSIS, Science Citation Index, the Cochrane Library, the Health Management Information Consortium and the Health Technology Assessment Database. RESULTS: Twenty-one observational studies enrolling 53,762 people reported the general prognostic value of SPECT MPS. In multivariate analysis, SPECT MPS variables yielded both independent and incremental value to combinations of clinical, ETT and angiographic variables in predicting cardiac death or non-fatal MI. Three comparative studies reported lower revascularization rates following a SPECT MPS-CA strategy (6-21%) compared with direct CA (16-44%). Four observational studies enrolling 2106 people reported the prognostic value of SPECT for patients following MI. In multivariate analysis including clinical history, ETT, SPECT MPS and angiographic variables, strategies involving SPECT MPS provided independent and incremental prognostic performance in predicting future cardiac events. CONCLUSIONS: SPECT MPS provides important additional information to that from ETT and/or CA that helps to risk-stratify patients with suspected or known CAD or following MI, enabling them to be managed more appropriately. Increasing the use of strategies involving SPECT MPS may identify lower risk patients for whom invasive CA might be avoided.

Systematic review of the effectiveness of home versus hospital or satellite unit hemodialysis for people with end-stage renal failure.

BACKGROUND: Home hemodialysis offers potential advantages over hospital hemodialysis, including the opportunity for more frequent and/or longer dialysis sessions. Expanding home hemodialysis services may help cope with the increasing numbers of people requiring hemodialysis. METHODS: We sought comparative studies or systematic reviews of home versus hospital/satellite unit hemodialysis for people with end-stage renal failure (ESRF). Outcomes included quality of life and survival. We searched MEDLINE, EMBASE, HealthSTAR, CINAHL, PREMEDLINE, and BIOSIS. Two reviewers independently extracted data and assessed the quality of the studies included. RESULTS: Twenty-seven studies of variable quality were included. People on home hemodialysis generally experienced a better quality of life and lived longer than those on hospital hemodialysis. Their partners, however, found home hemodialysis more stressful. Four studies using a Cox proportional hazards model to compare home with hospital hemodialysis reported a lower mortality risk for home hemodialysis. Of two studies using a Cox model to compare home with satellite unit hemodialysis, one reported a similar mortality risk, whereas the other reported a lower mortality risk for home hemodialysis. CONCLUSIONS: Home hemodialysis was generally associated with better outcomes than hospital hemodialysis and (more modestly so) satellite unit hemodialysis, in terms of quality of life, survival, and other measures of effectiveness. People on home hemodialysis, however, are a highly selected group. Home hemodialysis also provides the opportunity for more frequent and/or longer dialysis sessions than would otherwise be possible. It is difficult to disentangle the true effects of home hemodialysis from such influencing factors.

Prevalence of honorary and ghost authorship in Cochrane reviews.

CONTEXT: To determine the prevalence of honorary and ghost authorship in Cochrane reviews, how authorship is assigned, and the ways in which authors and Cochrane editorial teams contribute. METHODS: Using a Web-based, self-administered survey, corresponding authors for 577 reviews published in issues 1 and 2 from 1999 of The Cochrane Library were invited to report on the prevalence of honorary and ghost authors, contributions by authors listed in the byline and members of Cochrane editorial teams, and identification of methods of assigning authorship. Responses were received for 362 reviews (63% response rate), which contained 913 authors. RESULTS: One hundred forty-one reviews (39%) had evidence of honorary authors, 32 (9%) had evidence of ghost authors (most commonly a member of the Cochrane editorial team), and 9 (2%) had evidence of both honorary and ghost authors. The editorial teams contributed in a wide variety of ways to 301 reviews (83%). Authorship was decided by the group of authors (31%) or lead author (25%) in most reviews. Authorship order was assigned according to contribution in most reviews (76%). The 3 functions contributed to most by those listed in the byline were assessing the quality of included studies (83%), interpreting data (82%), and abstracting data from included studies (77%). CONCLUSIONS: A substantial proportion of reviews had evidence of honorary and ghost authorship. The Cochrane editorial teams contributed to most Cochrane reviews.