G Mowatt

Changing Provider Behavior: An Overview of Systematic Reviews of Interventions

Background.Increasing recognition of the failure to translate research findings into practice has led to greater awareness of the importance of using active dissemination and implementation strategies. Although there is a growing body of research evidence about the effectiveness of different strategies, this is not easily accessible to policy makers and professionals. Objectives.To identify, appraise, and synthesize systematic reviews of professional educational or quality assurance interventions to improve quality of care. Research design. An overview was made of systematic reviews of professional behavior change interventions published between 1966 and 1998. Results.Forty-one reviews were identified covering a wide range of interventions and behaviors. In general, passive approaches are generally ineffective and unlikely to result in behavior change. Most other interventions are effective under some circumstances; none are effective under all circumstances. Promising approaches include educational outreach (for prescribing) and reminders. Multifaceted interventions targeting different barriers to change are more likely to be effective than single interventions. Conclusions.Although the current evidence base is incomplete, it provides valuable insights into the likely effectiveness of different interventions. Future quality improvement or educational activities should be informed by the findings of systematic reviews of professional behavior change interventions.

64-Slice computed tomography angiography in the diagnosis and assessment of coronary artery disease: systematic review and meta-analysis

Context: Coronary artery disease (CAD) is a major cause of mortality and ill health. Objective: To assess whether 64-slice CT angiography might replace some coronary angiography (CA) for diagnosis and assessment of CAD. Data sources: Electronic databases, conference proceedings and reference lists of included studies. Study selection: 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 extraction: Two reviewers independently extracted data from included studies. Results: Forty studies were included; 28 provided sufficient data for inclusion in the meta-analyses, all using a cut off point 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 64–100%) and negative predictive value (NPV) 100% (range 86–100%). 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 PPV across studies 76% (range 44–93%) and NPV 99% (range 95–100%). 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.

Systematic review of sacral nerve stimulation for faecal incontinence and constipation.

This systematic review assesses the efficacy and safety of sacral nerve stimulation (SNS) for faecal incontinence and constipation. Electronic databases and selected websites were searched for studies evaluating SNS in the treatment of faecal incontinence or constipation. Primary outcome measures included episodes of faecal incontinence per week (faecal incontinence studies) and number of evacuations per week (constipation studies).

Efficacy and safety of using mesh or grafts in surgery for anterior and/or posterior vaginal wall prolapse: systematic review and meta‐analysis

Background  The efficacy and safety of mesh/graft in surgery for anterior or posterior pelvic organ prolapse is uncertain.

Systematic review of foam sclerotherapy for varicose veins

Foam sclerotherapy is a potential treatment for varicose veins. A systematic review was undertaken to assess its safety and efficacy.

Systematic review of the clinical effectiveness and cost-effectiveness of photodynamic diagnosis and urine biomarkers (FISH, ImmunoCyt, NMP22) and cytology for the detection and follow-up of bladder cancer.

OBJECTIVE To assess the clinical effectiveness and cost-effectiveness of photodynamic diagnosis (PDD) compared with white light cystoscopy (WLC), and urine biomarkers [fluorescence in situ hybridisation (FISH), ImmunoCyt, NMP22] and cytology for the detection and follow-up of bladder cancer. DATA SOURCES Major electronic databases including MEDLINE, MEDLINE In-Process, EMBASE, BIOSIS, Science Citation Index, Health Management Information Consortium and the Cochrane Controlled Trials Register were searched until April 2008. REVIEW METHODS A systematic review of the literature was carried out according to standard methods. An economic model was constructed to assess the cost-effectiveness of alternative diagnostic and follow-up strategies for the diagnosis and management of patients with bladder cancer. RESULTS In total, 27 studies reported PDD test performance. In pooled estimates [95% confidence interval (CI)] for patient-level analysis, PDD had higher sensitivity than WLC [92% (80% to 100%) versus 71% (49% to 93%)] but lower specificity [57% (36% to 79%) versus 72% (47% to 96%)]. Similar results were found for biopsy-level analysis. The median sensitivities (range) of PDD and WLC for detecting lower risk, less aggressive tumours were similar for patient-level detection [92% (20% to 95%) versus 95% (8% to 100%)], but sensitivity was higher for PDD than for WLC for biopsy-level detection [96% (88% to 100%) versus 88% (74% to 100%)]. For more aggressive, higher-risk tumours the median sensitivity of PDD for both patient-level [89% (6% to 100%)] and biopsy-level [99% (54% to 100%)] detection was higher than those of WLC [56% (0% to 100%) and 67% (0% to 100%) respectively]. Four RCTs comparing PDD with WLC reported effectiveness outcomes. PDD use at transurethral resection of bladder tumour resulted in fewer residual tumours at check cystoscopy [relative risk, RR, 0.37 (95% CI 0.20 to 0.69)] and longer recurrence-free survival [RR 1.37 (95% CI 1.18 to 1.59)] compared with WLC. In 71 studies reporting the performance of biomarkers and cytology in detecting bladder cancer, sensitivity (95% CI) was highest for ImmunoCyt [84% (77% to 91%)] and lowest for cytology [44% (38% to 51%)], whereas specificity was highest for cytology [96% (94% to 98%)] and lowest for ImmunoCyt [75% (68% to 83%)]. In the cost-effectiveness analysis the most effective strategy in terms of true positive cases (44) and life-years (11.66) [flexible cystoscopy (CSC) and ImmunoCyt followed by PDD in initial diagnosis and CSC followed by WLC in follow-up] had an incremental cost per life-year of over 270,000 pounds. The least effective strategy [cytology followed by WLC in initial diagnosis (average cost over 20 years 1403 pounds, average life expectancy 11.59)] was most likely to be considered cost-effective when societys willingness to pay was less than 20,000 pounds per life-year. No strategy was cost-effective more than 50% of the time, but four of the eight strategies in the probabilistic sensitivity analysis (three involving a biomarker or PDD) were each associated with a 20% chance of being considered cost-effective. In sensitivity analyses the results were most sensitive to the pretest probability of disease (5% in the base case). CONCLUSIONS The advantages of PDDs higher sensitivity in detecting bladder cancer have to be weighed against the disadvantages of a higher false-positive rate. Taking into account the assumptions made in the model, strategies involving biomarkers and/or PDD provide additional benefits at a cost that society might be willing to pay. Strategies replacing WLC with PDD provide more life-years but it is unclear whether they are worth the extra cost.

Systematic review of the clinical effectiveness and cost-effectiveness of rapid point-of-care tests for the detection of genital chlamydia infection in women and men

OBJECTIVE To assess whether or not the Chlamydia Rapid Test (CRT) could improve detection of genital chlamydia, and whether it is more effective than current practice using nucleic acid amplification tests (NAATs), in terms of the number of cases of chlamydia that are detected and treated and the proportion of partners identified and treated. DATA SOURCES Eleven electronic bibliographic databases (including MEDLINE and EMBASE) were searched until November 2008, as well as relevant websites. REVIEW METHODS Studies of sexually active adolescent and adult women and men suspected of having or being tested for genital chlamydia infection were considered. The tests considered were the CRT and other comparator point-of-care tests identified, using a NAAT as a reference standard. Summary sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratios for each model were reported as a median and a 95% confidence interval (CI). Effectiveness was measured in terms of the absolute numbers of true-positives, false-positives, false-negatives (and other positive cases missed) and true-negatives detected. Costs were considered from the health services perspective. Incremental cost-effectiveness ratios were used to examine the relative cost-effectiveness, and values of the major parameters of the models were varied in a sensitivity analysis. RESULTS Thirteen studies enrolling 8817 participants were included in the analysis. In the pooled estimates for the CRT, sensitivity (95% CI) was 80% (73% to 85%) for vaginal swab specimens and 77% (59% to 89%) for first void urine (FVU) specimens. Specificity was 99% (99% to 100%) for vaginal swab specimens and 99% (98% to 99%) for FVU specimens. In the pooled estimates for a comparator point-of-care test (Clearview Chlamydia), sensitivity (95% CI) was 52% (39% to 65%) for vaginal, cervical and urethral swab specimens combined, and 64% (47% to 77%) for cervical specimens alone. Specificity was 97% (94% to 100%) for vaginal, cervical and urethral swab specimens combined, and 97% (88% to 99%) for cervical specimens alone. The results of the economic evaluation showed that for a hypothetical cohort of 1000 people, using the current practice of polymerase chain reaction testing would result in 12.63 people who were offered testing being correctly treated and having their sexual partners contacted, at a cost of 7070 pounds (for the whole cohort). For the CRT, the number being correctly treated would be 10.98, at a cost of 7180 pounds. For the Clearview Chlamydia test, the number correctly treated would be 7.14, at a cost of 7170 pounds. Both point-of-care tests were therefore more costly and less effective than current practice. CONCLUSIONS The limited evidence available suggests that NAATs are still the most accurate and cost-effective method for diagnosing chlamydia infection. There may be circumstances in which point-of-care tests could be provided in addition to existing NAAT services, but there is currently little evidence on point-of-care methods in such settings. Robust evidence of the diagnostic accuracy of point-of-care tests for different types of samples is also still required, as are studies evaluating clinical effectiveness outcomes for these tests in comparison with NAATs.

Systematic review and economic modelling of the relative clinical benefit and cost-effectiveness of laparoscopic surgery and robotic surgery for removal of the prostate in men with localised prostate cancer

BACKGROUND Complete surgical removal of the prostate, radical prostatectomy, is the most frequently used treatment option for men with localised prostate cancer. The use of laparoscopic (keyhole) and robot-assisted surgery has improved operative safety but the comparative effectiveness and cost-effectiveness of these options remains uncertain. OBJECTIVE This study aimed to determine the relative clinical effectiveness and cost-effectiveness of robotic radical prostatectomy compared with laparoscopic radical prostatectomy in the treatment of localised prostate cancer within the UK NHS. DATA SOURCES MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, BIOSIS, Science Citation Index and Cochrane Central Register of Controlled Trials were searched from January 1995 until October 2010 for primary studies. Conference abstracts from meetings of the European, American and British Urological Associations were also searched. Costs were obtained from NHS sources and the manufacturer of the robotic system. Economic model parameters and distributions not obtained in the systematic review were derived from other literature sources and an advisory expert panel. REVIEW METHODS Evidence was considered from randomised controlled trials (RCTs) and non-randomised comparative studies of men with clinically localised prostate cancer (cT1 or cT2); outcome measures included adverse events, cancer related, functional, patient driven and descriptors of care. Two reviewers abstracted data and assessed the risk of bias of the included studies. For meta-analyses, a Bayesian indirect mixed-treatment comparison was used. Cost-effectiveness was assessed using a discrete-event simulation model. RESULTS The searches identified 2722 potentially relevant titles and abstracts, from which 914 reports were selected for full-text eligibility screening. Of these, data were included from 19,064 patients across one RCT and 57 non-randomised comparative studies, with very few studies considered at low risk of bias. The results of this study, although associated with some uncertainty, demonstrated that the outcomes were generally better for robotic than for laparoscopic surgery for major adverse events such as blood transfusion and organ injury rates and for rate of failure to remove the cancer (positive margin) (odds ratio 0.69; 95% credible interval 0.51 to 0.96; probability outcome favours robotic prostatectomy = 0.987). The predicted probability of a positive margin was 17.6% following robotic prostatectomy compared with 23.6% for laparoscopic prostatectomy. Restriction of the meta-analysis to studies at low risk of bias did not change the direction of effect but did decrease the precision of the effect size. There was no evidence of differences in cancer-related, patient-driven or dysfunction outcomes. The results of the economic evaluation suggested that when the difference in positive margins is equivalent to the estimates in the meta-analysis of all included studies, robotic radical prostatectomy was on average associated with an incremental cost per quality-adjusted life-year that is less than threshold values typically adopted by the NHS (£30,000) and becomes further reduced when the surgical capacity is high. LIMITATIONS The main limitations were the quantity and quality of the data available on cancer-related outcomes and dysfunction. CONCLUSIONS This study demonstrated that robotic prostatectomy had lower perioperative morbidity and a reduced risk of a positive surgical margin compared with laparoscopic prostatectomy although there was considerable uncertainty. Robotic prostatectomy will always be more costly to the NHS because of the fixed capital and maintenance charges for the robotic system. Our modelling showed that this excess cost can be reduced if capital costs of equipment are minimised and by maintaining a high case volume for each robotic system of at least 100-150 procedures per year. This finding was primarily driven by a difference in positive margin rate. There is a need for further research to establish how positive margin rates impact on long-term outcomes. FUNDING The National Institute for Health Research Health Technology Assessment programme.

The diagnostic accuracy and cost-effectiveness of magnetic resonance spectroscopy and enhanced magnetic resonance imaging techniques in aiding the localisation of prostate abnormalities for biopsy: a systematic review and economic evaluation.

BACKGROUND In the UK, prostate cancer (PC) is the most common cancer in men. A diagnosis can be confirmed only following a prostate biopsy. Many men find themselves with an elevated prostate-specific antigen (PSA) level and a negative biopsy. The best way to manage these men remains uncertain. OBJECTIVES To assess the diagnostic accuracy of magnetic resonance spectroscopy (MRS) and enhanced magnetic resonance imaging (MRI) techniques [dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted MRI (DW-MRI)] and the clinical effectiveness and cost-effectiveness of strategies involving their use in aiding the localisation of prostate abnormalities for biopsy in patients with prior negative biopsy who remain clinically suspicious for harbouring malignancy. DATA SOURCES Databases searched--MEDLINE (1946 to March 2012), MEDLINE In-Process & Other Non-Indexed Citations (March 2012), EMBASE (1980 to March 2012), Bioscience Information Service (BIOSIS; 1995 to March 2012), Science Citation Index (SCI; 1995 to March 2012), The Cochrane Library (Issue 3 2012), Database of Abstracts of Reviews of Effects (DARE; March 2012), Medion (March 2012) and Health Technology Assessment database (March 2012). REVIEW METHODS Types of studies: direct studies/randomised controlled trials reporting diagnostic outcomes. INDEX TESTS MRS, DCE-MRI and DW-MRI. Comparators: T2-weighted magnetic resonance imaging (T2-MRI), transrectal ultrasound-guided biopsy (TRUS/Bx). Reference standard: histopathological assessment of biopsied tissue. A Markov model was developed to assess the cost-effectiveness of alternative MRS/MRI sequences to direct TRUS-guided biopsies compared with systematic extended-cores TRUS-guided biopsies. A health service provider perspective was adopted and the recommended 3.5% discount rate was applied to costs and outcomes. RESULTS A total of 51 studies were included. In pooled estimates, sensitivity [95% confidence interval (CI)] was highest for MRS (92%; 95% CI 86% to 95%). Specificity was highest for TRUS (imaging test) (81%; 95% CI 77% to 85%). Lifetime costs ranged from £3895 using systematic TRUS-guided biopsies to £4056 using findings on T2-MRI or DCE-MRI to direct biopsies (60-year-old cohort, cancer prevalence 24%). The base-case incremental cost-effectiveness ratio for T2-MRI was <£30,000 per QALY (all cohorts). Probabilistic sensitivity analysis showed high uncertainty surrounding the incremental cost-effectiveness of T2-MRI in moderate prevalence cohorts. The cost-effectiveness of MRS compared with T2-MRI and TRUS was sensitive to several key parameters. LIMITATIONS Non-English-language studies were excluded. Few studies reported DCE-MRI/DW-MRI. The modelling was hampered by limited data on the relative diagnostic accuracy of alternative strategies, the natural history of cancer detected at repeat biopsy, and the impact of diagnosis and treatment on disease progression and health-related quality of life. CONCLUSIONS MRS had higher sensitivity and specificity than T2-MRI. Relative cost-effectiveness of alternative strategies was sensitive to key parameters/assumptions. Under certain circumstances T2-MRI may be cost-effective compared with systematic TRUS. If MRS and DW-MRI can be shown to have high sensitivity for detecting moderate/high-risk cancer, while negating patients with no cancer/low-risk disease to undergo biopsy, their use could represent a cost-effective approach to diagnosis. However, owing to the relative paucity of reliable data, further studies are required. In particular, prospective studies are required in men with suspected PC and elevated PSA levels but previously negative biopsy comparing the utility of the individual and combined components of a multiparametric magnetic resonance (MR) approach (MRS, DCE-MRI and DW-MRI) with both a MR-guided/-directed biopsy session and an extended 14-core TRUS-guided biopsy scheme against a reference standard of histopathological assessment of biopsied tissue obtained via saturation biopsy, template biopsy or prostatectomy specimens. STUDY REGISTRATION PROSPERO number CRD42011001376. FUNDING The National Institute for Health Research Health Technology Assessment programme.

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.