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.

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.

Outcomes of ureteroscopy for stone disease in pregnancy: results from a systematic review of the literature.

INTRODUCTION: Our aim was to evaluate the clinical efficacy and safety of ureteroscopy as a primary treatment for pregnant women with symptomatic ureteric stones who have failed conservative management. MATERIALS AND METHODS: A systematic review of the literature from January 1990 to June 2011 was performed, including all English language articles. Outcome measures were clinical efficacy, in terms of stone clearance and need for additional procedures, and safety in terms of complications. RESULTS: A total of 239 abstracts were screened and 15 studies were identified reporting on 116 procedures. The surgical methods of stone management employed were stone extraction with basket only (n = 55, 47%), laser fragmentation (n = 27, 23%; holmium, n = 20, pulse dye, n = 7), impact lithotripsy (n = 21, 18%), ureteroscopic lithotripsy (n = 6, 5%) and a combination of methods (n = 6, 5%). A post-operative stent was inserted in 64 of 116 procedures (55%). Complete stone clearance was seen in 100 of the 116 procedures (86%). There were 2 major complications (1 ureteral perforation and 1 case of premature uterine contraction) and 7 minor complications (5 urinary tract infections and 2 cases of post-operative pain). CONCLUSION: This review suggests that stone clearance using ureteroscopy is a relatively safe option in pregnancy with a high success rate.

Types of urethral catheters for management of short-term voiding problems in hospitalized adults: a short version Cochrane review.

BACKGROUND: Urinary tract infection (UTI) is the most common hospital acquired infection. The major associated cause is indwelling urinary catheters. Currently there are many types of catheters available. A variety of specialized urethral catheters have been designed to reduce the risk of infection. These include antiseptic impregnated catheters and antibiotic impregnated catheters. Other issues that should be considered when choosing a catheter are ease of use, comfort and cost. OBJECTIVES: The primary objective of this review was to determine the effect of type of indwelling urethral catheter on the risk of urinary tract infection in adults who undergo short-term urinary catheterization. METHODS: We searched the Specialized Trials Register of the Cochrane Incontinence Group (searched September 11, 2007). We also examined the bibliographies of relevant articles and contacted catheter manufacturer representatives for trials. All randomized and quasi-randomized trials comparing types of indwelling urinary catheters for short-term catheterization in hospitalized adults. Short-term catheterization was defined as up to and including 14 days, or other temporary short-term use as defined by the trialists (for example <21 days with data time points at 7-day intervals). Data were extracted by one reviewer and independently verified by a second reviewer for both the original review and for the update. Disagreements were resolved by discussion. Data were processed as described in the Cochrane Handbook. Where data in trials were not fully reported, clarification was sought directly from the trialists (secondary sources were used to confirm results of one trial). RESULTS: Twenty-three trials met the inclusion criteria involving 5,236 hospitalized adults in 22 parallel group trials and 27,878 adults in one large cluster-randomized cross-over trial. The antiseptic catheters were either impregnated with silver oxide or silver alloy. Silver oxide catheters were not associated with a statistically significant reduction in bacteriuria in short-term catheterized hospitalized adults but the confidence intervals were wide (RR 0.89, 95% CI 0.68-1.15) and these catheters are no longer available. Silver alloy catheters were found to significantly reduce the incidence of asymptomatic bacteriuria (RR 0.54, 95% CI 0.43-0.67) in hospitalized adults catheterized for <1 week. At >1 week of catheterization the risk of asymptomatic bacteriuria was still reduced with the use of silver alloy catheters (RR 0.64, 95% CI 0.51-0.80). The randomized cross-over trial of silver alloy catheters versus standard catheters was excluded from the pooled results because data were not available prior to crossover. The results of this trial indicated benefit from the silver alloy catheters and included an economic analysis that indicated cost savings of between 3.3% and 35.5%. Antibiotic impregnated catheters were compared to standard catheters and found to lower the rate of asymptomatic bacteriuria in the antibiotic group at <1 week of catheterization for both minocycline and rifampicin combined (RR 0.36, 95% CI 0.18-0.73), and nitrofurazone (RR 0.52, 95% CI 0.34-0.78). However, at >1 week the results were not statistically significant. One of 56 men in the antibiotic impregnated group had a symptomatic UTI compared with 6 of 68 who had standard catheters (RR 0.20, 95% CI 0.03-1.63). Three trials compared two different types of standard catheters (defined as catheters that are not impregnated with antiseptics or antibiotics) to investigate infection. Individual trials were too small to show whether or not one type of standard catheter reduced the risk of catheter related urinary tract infection compared to another type of standard catheter. CONCLUSIONS: The results suggest that the use of silver alloy indwelling catheters for catheterizing hospitalized adults short-term reduces the risk of catheter acquired urinary tract infection. Further economic evaluation is required to confirm that the reduction of infection compensates for the increased cost of silver alloy catheters. Catheters impregnated with antibiotics are also beneficial in reducing bacteriuria in hospitalized adults catheterized for <1 week but the data were too few to draw conclusions about those catheterized for longer. There was not enough evidence to suggest whether or not any standard catheter was better than another in terms of reducing the risk of urinary tract infection in hospitalized adults catheterized short-term. Siliconized catheters may be less likely to cause urethral side effects in men; however, this result should be interpreted with some caution as the trials were small and the outcome definitions and specific catheters compared varied.

Types of urethral catheters for management of short-term voiding problems in hospitalised adults.

BACKGROUND: Urinary tract infection (UTI) is the most common hospital acquired infection. The major associated cause is indwelling urinary catheters. Currently there are many types of catheters available. A variety of specialised urethral catheters have been designed to reduce the risk of infection. These include antiseptic impregnated catheters and antibiotic impregnated catheters. Other issues that should be considered when choosing a catheter are ease of use, comfort and cost. OBJECTIVES: The primary objective of this review was to determine the effect of type of indwelling urethral catheter on the risk of urinary tract infection in adults who undergo short-term urinary catheterisation. SEARCH STRATEGY: We searched the Specialised Trials Register of the Cochrane Incontinence Group (searched 11 September 2007). We also examined the bibliographies of relevant articles and contacted catheter manufacturer representatives for trials. SELECTION CRITERIA: All randomised and quasi randomised trials comparing types of indwelling urinary catheters for short-term catheterisation in hospitalised adults. Short-term catheterisation was defined as up to and including fourteen days, or other temporary short-term use as defined by the trialists (for example less than 21 days with data time points at 7 day intervals). DATA COLLECTION AND ANALYSIS: Data were extracted by one reviewer and independently verified by a second reviewer. Disagreements were resolved by discussion. Data were processed as described in the Cochrane Handbook. Where data in trials were not fully reported, clarification was sought directly from the trialists (secondary sources were used to confirm results of one trial). MAIN RESULTS: Twenty three trials met the inclusion criteria involving 5236 hospitalised adults in 22 parallel group trials and 27,878 adults in one large cluster-randomised cross-over trial. The antiseptic catheters were either impregnated with silver oxide or silver alloy. Silver oxide catheters were not associated with a statistically significant reduction in bacteriuria in short-term catheterised hospitalised adults but the confidence intervals were wide (RR 0.89, 95% CI 0.68 to 1.15) and these catheters are no longer available. Silver alloy catheters were found to significantly reduce the incidence of asymptomatic bacteriuria (RR 0.54, 95% CI 0.43 to 0.67) in hospitalised adults catheterised for less than one week. At greater than one week of catheterisation the risk of asymptomatic bacteriuria was still reduced with the use of silver alloy catheters (RR 0.64, 95% CI 0.51 to 0.80). The randomised cross-over trial of silver alloy catheters versus standard catheters was excluded from the pooled results because data were not available prior to crossover. The results of this trial indicated benefit from the silver alloy catheters and included an economic analysis that indicated cost savings of between 3.3 per cent and 35.5 per cent. Antibiotic impregnated catheters were compared to standard catheters and found to lower the rate of asymptomatic bacteriuria in the antibiotic group at less than one week of catheterisation for both minocycline and rifampicin (RR 0.36, 95% CI 0.18 to 0.73), and nitrofurazone (RR 0.52, 95% CI 0.34 to 0.78). However, at greater than one week the results were not statistically significant. One of 56 men in the antibiotic impregnated group had a symptomatic UTI compared with 6 of 68 who had standard catheters (RR 0.20, 95% CI 0.03 to 1.63). Three trials compared two different types of standard catheters (defined as catheters that are not impregnated with antiseptics or antibiotics) to investigate infection. Individual trials were too small to show whether or not one type of standard catheter reduced the risk of catheter related urinary tract infection compared to another type of standard catheter. AUTHORS' CONCLUSIONS: The results suggest that the use of silver alloy indwelling catheters for catheterising hospitalised adults short-term reduces the risk of catheter acquired urinary tract infection. Further economic evaluation is required to confirm that the reduction of infection compensates for the increased cost of silver alloy catheters.Catheters impregnated with antibiotics are also beneficial in reducing bacteriuria in hospitalised adults catheterised for less than one week but the data were too few to draw conclusions about those catheterised for longer. There was not enough evidence to suggest whether or not any standard catheter was better than another in terms of reducing the risk of urinary tract infection in hospitalised adults catheterised short-term. Siliconised catheters may be less likely to cause urethral side effects in men; however, this result should be interpreted with some caution as the trials were small and the outcome definitions and specific catheters compared varied.

A mathematical model of phytoremediation for petroleum contaminated soil: sensitivity analysis.

Phytoremediation is an attractive treatment technology for many contaminated sites due to its cost effectiveness and public acceptance. We present a sensitivity analysis of important parameters from a screening level model for phytoremediation by grass species of weathered petroleum-contaminated sites. The conceptual framework is that root movement through contaminated soil will enhance contaminant biodegradation by providing a local environment more favorable for petroleum degrading microorganisms--the so-called rhizosphere effect. Common questions in phytoremediation are, "What species should be planted?" and "What management practices should be followed?" These choices may affect degradation kinetics, root biomass (and therefore rhizosphere volume), and the root turnover. Important model parameters are the rate constants, rhizosphere volume, and the rate of root turnover. We present a sensitivity analysis with the aim of identifying the most important factors for improving phytoremediation effectiveness. For simulations of the phytoremediation of weathered diesel range organics, our results indicate that annual species, with higher root turnover, are preferred over perennial species with the caveat of equal degradation rate constants, that is, no species-dependent effects. In addition, the results suggest that the management of nonrhizosphere soil could play an important role in the overall effectiveness of phytoremediation. Finally, the effect of increasing root biomass or increasing the rhizosphere thickness is approximately equivalent with respect to the ultimate removal of the contaminants.

A mathematical model of phytoremediation for petroleum-contaminated soil: model development.

We present a simple model for root length density that combines the generally accepted spatial (exponential decrease with depth) and temporal (sinusoidal) variability of root length. Parameters in this model for root length density can be determined from assumed or measured information regarding the annual biomass turnover, maximum standing biomass, and maximum depth of root penetration. The root length density model, coupled with information regarding the average root lifespan, gives specific root growth and senescence functions that are the forcing functions for the phytoremediation model. We present a screening level mathematical model for phytoremediation that accounts for the growth and senescence of roots in the system. This is an important factor for recalcitrant, immobile compounds found in weathered crude oil contaminated soils. The phytoremediation model is based on variable volume compartments that have individual first-order degradation rate constants; as the roots move through the soil, the soil cycles through the rhizosphere zone, decaying root zone and bulk soil zone. Thus, although the oil is immobile, as the roots penetrate through the soil the oil is brought into contact with the rhizosphere.

Bonding of hydroxycinnamic acids to lignin: ferulic and p-coumaric acids are predominantly linked at the benzyl position of lignin, not the beta-position, in grass cell walls.

A suspension in dichloromethane-water (18:1, v/v) of various fractions containing hydroxycinnamic acid ester-ether bridges between lignin and polysaccharides prepared from cell walls of matured oat (Avena sativa L.) intemodes, and a solution of their acetates in the same solvent, were treated with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). This reagent selectively cleaves benzyl ether and ester linkages of negatively charged aromatic nuclei. The sample treated with DDQ was directly hydrolysed either under mild (1 M NaOH, overnight at 37 degrees C) or severe (4 M NaOH, for 2 h at 170 degrees C) conditions. The hydroxycinnamic acids released in the hydrolysate were methylated with diazomethane and analysed quantitatively using gas chromatography. Significant portions of ether linkages between hydroxycinnamic acids and lignin were cleaved with DDQ, which suggests that most of the hydroxycinnamic acids were ether-linked at the benzyl position, and not the beta-position, of the lignin side chain as previously claimed.