Cost-effectiveness of strategies to improve HCV screening, linkage-to-care and treatment in remand prison settings in England.

BACKGROUND: A simplified cascade-of-care may improve screening and treatment uptake among incarcerated individuals. We assessed the cost-effectiveness of traditional and simplified screening and treatment in a London remand prison. METHODS: Using empirical data from Her Majesty's Prison (HMP) Wormwood Scrubs, London, we designed a decision tree and Markov transition state model using national average data for HCV screening and treatment for the base-case scenario. This compared two alternative strategies; (a) general prison population screening and treatment and (b) prioritising screening and treatment among people who inject drugs (PWID) combined with general prison population screening and treatment. Strategies varied the rates of screening (47%-90%), linkage-to-care (60%-86%) and treatment (21%-85%). Cost, utility and disease transition rates were obtained from existing literature. Outcome measures were as follows: screening, treatment and disease-related costs per admitted individual, quality-adjusted life years (QALYs). Incremental cost-effectiveness ratios (ICERs) were calculated for each intervention. All costs and utilities were discounted at a rate of 3.5% per annum. Both univariate and probabilistic sensitivity analyses have been conducted. RESULTS: In our cohort of 5239 incarcerated individuals with an estimated chronic HCV prevalence of 2.6%, all strategy ICER values (£3565-10 300) fell below the national willingness to pay threshold (£30 000). Increased successful treatment (7%-54%) was observed by an optimising cascade-of-care. A robust sensitivity analysis identified treatment cost of, QALY for mild liver disease and probability of completing treatment as important factors that impact the ICER value. CONCLUSION: In our remand setting, optimising adherence to the cascade-of-care is cost-effective. Where universal screening is not practical, a stratified approach focused on intensive screening and treatment of PWID also results in increased treatment uptake and is highly cost-effective.

Antibiotics and antiseptics for venous leg ulcers.

BACKGROUND: Venous leg ulcers are a type of chronic wound affecting up to 1% of adults in developed countries at some point during their lives. Many of these wounds are colonised by bacteria or show signs of clinical infection. The presence of infection may delay ulcer healing. Two main strategies are used to prevent and treat clinical infection in venous leg ulcers: systemic antibiotics and topical antibiotics or antiseptics. OBJECTIVES: The objective of this review was to determine the effects of systemic antibiotics and topical antibiotics and antiseptics on the healing of venous ulcers. SEARCH METHODS: In May 2013, for this second update, we searched the Cochrane Wounds Group Specialised Register (searched 24 May 2013); the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 4); Ovid MEDLINE (1948 to Week 3 May 2013); Ovid MEDLINE (In-Process & Other Non-indexed Citations, 22 May 2013); Ovid EMBASE (1980 to Week 20 2013); and EBSCO CINAHL (1982 to 17 May 2013). No language or publication date restrictions were applied. SELECTION CRITERIA: Randomised controlled trials (RCTs) recruiting people with venous leg ulceration, evaluating at least one systemic antibiotic, topical antibiotic or topical antiseptic that reported an objective assessment of wound healing (e.g. time to complete healing, frequency of complete healing, change in ulcer surface area) were eligible for inclusion. Selection decisions were made by two review authors while working independently. DATA COLLECTION AND ANALYSIS: Information on the characteristics of participants, interventions and outcomes was recorded on a standardised data extraction form. In addition, aspects of trial methods were extracted, including randomisation, allocation concealment, blinding of participants and outcome assessors, incomplete outcome data and study group comparability at baseline. Data extraction and validity assessment were conducted by one review author and were checked by a second. Data were pooled when appropriate. MAIN RESULTS: Forty-five RCTs reporting 53 comparisons and recruiting a total of 4486 participants were included, Many RCTs were small, and most were at high or unclear risk of bias. Ulcer infection status at baseline and duration of follow-up varied across RCTs. Five RCTs reported eight comparisons of systemic antibiotics, and the remainder evaluated topical preparations: cadexomer iodine (11 RCTs reporting 12 comparisons); povidone-iodine (six RCTs reporting seven comparisons); peroxide-based preparations (four RCTs reporting four comparisons); honey-based preparations (two RCTs reporting two comparisons); silver-based preparations (12 RCTs reporting 13 comparisons); other topical antibiotics (three RCTs reporting five comparisons); and other topical antiseptics (two RCTs reporting two comparisons). Few RCTs provided a reliable estimate of time to healing; most reported the proportion of participants with complete healing during the trial period. Systemic antibioticsMore participants were healed when they were prescribed levamisole (normally used to treat roundworm infection) compared with placebo: risk ratio (RR) 1.31 (95% CI 1.06 to 1.62). No between-group differences were detected in terms of complete healing for other comparisons: antibiotics given according to antibiogram versus usual care; ciprofloxacin versus standard care/placebo; trimethoprim versus placebo; ciprofloxacin versus trimethoprim; and amoxicillin versus topical povidone-iodine. Topical antibiotics and antiseptics Cadexomer iodine: more participants were healed when given cadexomer iodine compared with standard care. The pooled estimate from four RCTs for complete healing at four to 12 weeks was RR 2.17 (95% CI 1.30 to 3.60). No between-group differences in complete healing were detected when cadexomer iodine was compared with the following: hydrocolloid dressing; paraffin gauze dressing; dextranomer; and silver-impregnated dressings.Povidone iodine: no between-group differences in complete healing were detected when povidone-iodine was compared with the following: hydrocolloid; moist or foam dressings according to wound status; and growth factor. Time to healing estimates for povidone-iodine versus dextranomer, and for povidone-iodine versus hydrocolloid, were likely to be unreliable.Peroxide-based preparations: four RCTs reported findings in favour of peroxide-based preparations when compared with usual care for surrogate healing outcomes (change in ulcer area). There was no report of complete healing.Honey-based preparations: no between-group difference in time to healing or complete healing was detected for honey-based products when compared with usual care.Silver-based preparations: no between-group differences in complete healing were detected when 1% silver sulphadiazine ointment was compared with standard care/placebo and tripeptide copper complex; or when different brands of silver-impregnated dressings were compared; or when silver-impregnated dressings were compared with non-antimicrobial dressings.Other topical antibiotics: data from one RCT suggested that more participants healed at four weeks when treated with an enzymatic cleanser (a non-antibiotic preparation) compared with a chloramphenicol-containing ointment (additional active ingredients also included in the ointment): RR 0.13 (95% CI 0.02 to 0.99). No between-group differences in complete healing were detected for framycetin sulphate ointment versus enzymatic cleanser; chloramphenicol ointment versus framycetin sulphate ointment; mupirocin ointment versus vehicle; and topical antibiotics given according to antibiogram versus an herbal ointment.Other topical antiseptics: data from one RCT suggested that more participants receiving an antiseptic ointment (ethacridine lactate) had responsive ulcers (defined as > 20% reduction in area) at four weeks when compared with placebo: RR 1.45 (95% CI 1.21 to 1.73). Complete healing was not reported. No between-group difference was detected between chlorhexidine solution and usual care. AUTHORS' CONCLUSIONS: At present, no evidence is available to support the routine use of systemic antibiotics in promoting healing of venous leg ulcers. However, the lack of reliable evidence means that it is not possible to recommend the discontinuation of any of the agents reviewed. In terms of topical preparations, some evidence supports the use of cadexomer iodine. Current evidence does not support the routine use of honey- or silver-based products. Further good quality research is required before definitive conclusions can be drawn about the effectiveness of povidone-iodine, peroxide-based preparations, ethacridine lactate, chloramphenicol, framycetin, mupirocin, ethacridine or chlorhexidine in healing venous leg ulceration. In light of the increasing problem of bacterial resistance to antibiotics, current prescribing guidelines recommend that antibacterial preparations should be used only in cases of clinical infection, not for bacterial colonisation.

Antibiotics and antiseptics for venous leg ulcers.

BACKGROUND: Venous leg ulcers are a type of chronic wound affecting up to 1% of adults in developed countries at some point during their lives. Many of these wounds are colonised by bacteria or show signs of clinical infection. The presence of infection may delay ulcer healing. Two main strategies are used to prevent and treat clinical infection in venous leg ulcers: systemic antibiotics and topical antibiotics or antiseptics. OBJECTIVES: The objective of this review was to determine the effects of systemic antibiotics and topical antibiotics and antiseptics on the healing of venous ulcers; review authors also examined the effects of these interventions on clinical infection, bacterial flora, bacterial resistance, ulcer recurrence, adverse effects, patient satisfaction, health-related quality of life and costs. SEARCH METHODS: In May 2013, for this second update, we searched the Cochrane Wounds Group Specialised Register (searched 24 May 2013); the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 4); Ovid MEDLINE (1948 to Week 3 May 2013); Ovid MEDLINE (In-Process & Other Non-indexed Citations, 22 May 2013); Ovid EMBASE (1980 to Week 20 2013); and EBSCO CINAHL (1982 to 17 May 2013). No language or publication date restrictions were applied. SELECTION CRITERIA: Randomised controlled trials (RCTs) recruiting people with venous leg ulceration, evaluating at least one systemic antibiotic, topical antibiotic or topical antiseptic that reported an objective assessment of wound healing (e.g. time to complete healing, frequency of complete healing, change in ulcer surface area) were eligible for inclusion. Selection decisions were made by two review authors while working independently. DATA COLLECTION AND ANALYSIS: Information on the characteristics of participants, interventions and outcomes was recorded on a standardised data extraction form. In addition, aspects of trial methods were extracted, including randomisation, allocation concealment, blinding of participants and outcome assessors, incomplete outcome data and study group comparability at baseline. Data extraction and validity assessment were conducted by one review author and were checked by a second. Data were pooled when appropriate. MAIN RESULTS: Forty-five RCTs reporting 53 comparisons and recruiting a total of 4486 participants were included, Many RCTs were small, and most were at high or unclear risk of bias. Ulcer infection status at baseline and duration of follow-up varied across RCTs. Five RCTs reported eight comparisons of systemic antibiotics, and the remainder evaluated topical preparations: cadexomer iodine (11 RCTs reporting 12 comparisons); povidone-iodine (six RCTs reporting seven comparisons); peroxide-based preparations (four RCTs reporting four comparisons); honey-based preparations (two RCTs reporting two comparisons); silver-based preparations (12 RCTs reporting 13 comparisons); other topical antibiotics (three RCTs reporting five comparisons); and other topical antiseptics (two RCTs reporting two comparisons). Few RCTs provided a reliable estimate of time to healing; most reported the proportion of participants with complete healing during the trial period. Systemic antibioticsMore participants were healed when they were prescribed levamisole (normally used to treat roundworm infection) compared with placebo: risk ratio (RR) 1.31 (95% CI 1.06 to 1.62). No between-group differences were detected in terms of complete healing for other comparisons: antibiotics given according to antibiogram versus usual care; ciprofloxacin versus standard care/placebo; trimethoprim versus placebo; ciprofloxacin versus trimethoprim; and amoxicillin versus topical povidone-iodine. Topical antibiotics and antisepticsCadexomer iodine: more participants were healed when given cadexomer iodine compared with standard care. The pooled estimate from four RCTs for complete healing at four to 12 weeks was RR 2.17 (95% CI 1.30 to 3.60). No between-group differences in complete healing were detected when cadexomer iodine was compared with the following: hydrocolloid dressing; paraffin gauze dressing; dextranomer; and silver-impregnated dressings.Povidone iodine: no between-group differences in complete healing were detected when povidone-iodine was compared with the following: hydrocolloid; moist or foam dressings according to wound status; and growth factor. Time to healing estimates for povidone-iodine versus dextranomer, and for povidone-iodine versus hydrocolloid, were likely to be unreliable.Peroxide-based preparations: four RCTs reported findings in favour of peroxide-based preparations when compared with usual care for surrogate healing outcomes (change in ulcer area). There was no report of complete healing.Honey-based preparations: no between-group difference in time to healing or complete healing was detected for honey-based products when compared with usual care.Silver-based preparations: no between-group differences in complete healing were detected when 1% silver sulphadiazine ointment was compared with standard care/placebo and tripeptide copper complex; or when different brands of silver-impregnated dressings were compared; or when silver-impregnated dressings were compared with non-antimicrobial dressings.Other topical antibiotics: data from one RCT suggested that more participants healed at four weeks when treated with an enzymatic cleanser (a non-antibiotic preparation) compared with a chloramphenicol-containing ointment (additional active ingredients also included in the ointment): RR 0.13 (95% CI 0.02 to 0.99). No between-group differences in complete healing were detected for framycetin sulphate ointment versus enzymatic cleanser; chloramphenicol ointment versus framycetin sulphate ointment; mupirocin ointment versus vehicle; and topical antibiotics given according to antibiogram versus an herbal ointment.Other topical antiseptics: data from one RCT suggested that more participants receiving an antiseptic ointment (ethacridine lactate) had responsive ulcers (defined as > 20% reduction in area) at four weeks when compared with placebo: RR 1.45 (95% CI 1.21 to 1.73). Complete healing was not reported. No between-group difference was detected between chlorhexidine solution and usual care. AUTHORS' CONCLUSIONS: At present, no evidence is available to support the routine use of systemic antibiotics in promoting healing of venous leg ulcers. However, the lack of reliable evidence means that it is not possible to recommend the discontinuation of any of the agents reviewed. In terms of topical preparations, some evidence supports the use of cadexomer iodine. Current evidence does not support the routine use of honey- or silver-based products. Further good quality research is required before definitive conclusions can be drawn about the effectiveness of povidone-iodine, peroxide-based preparations, ethacridine lactate, chloramphenicol, framycetin, mupirocin, ethacridine or chlorhexidine in healing venous leg ulceration. In light of the increasing problem of bacterial resistance to antibiotics, current prescribing guidelines recommend that antibacterial preparations should be used only in cases of clinical infection, not for bacterial colonisation.

Intravesical botulinum toxin A injections in the treatment of painful bladder syndrome/interstitial cystitis: a systematic review.

INTRODUCTION AND HYPOTHESIS: Intravesical botulinum toxin A (BTX-A) is emerging as a potential new treatment for refractory interstitial cystitis (IC). However, there has been conflicting evidence on this treatment's effectiveness. The aim of our systematic review was to assess the effectiveness and adverse effects of intravesical BTX-A in IC. METHODS: Randomised controlled trials (RCTs) and prospective studies of relevance were identified, assessed for inclusion and then analysed by two independent reviewers. RESULTS: Ten (three RCTs and seven prospective cohort) studies with a total of 260 participants were included. Eight studies reported improvement in symptoms. Urodynamic parameters were variable. Meta-analysis was not performed due to heterogeneity in reporting of outcomes. Some adverse events, e.g. dysuria and voiding difficulty, were noted (19 out of 260 were required to self-catheterize at anytime postoperatively). CONCLUSIONS: The evidence from the studies thus far suggests a trend towards short-term benefit with intravesical BTX-A injections in refractory IC, but further robust evidence should be awaited.

Therapeutic ultrasound for venous leg ulcers.

BACKGROUND: Venous leg ulcers pose a significant burden for patients and healthcare systems. Ultrasound (US) may be a useful treatment for these ulcers. OBJECTIVES: To determine whether US increases the healing of venous leg ulcers. SEARCH STRATEGY: We searched the Cochrane Wounds Group Specialised Register (searched 24 February 2010); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2010); Ovid MEDLINE (1950 to February Week 2 2010); In-Process & Other Non-Indexed Citations (searched 24 February 2010); Ovid EMBASE 1980 to 2010 Week 07; EBSCO CINAHL 1982 to 24 February 2010. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing US with no US. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the search results and selected eligible studies. Details from included studies were summarised using a data extraction sheet, and double-checked. We tried to contact trial authors for missing data. MAIN RESULTS: Eight trials were included; all had unclear, or high, risks of bias, with differences in duration of follow-up, and US regimens. Six trials evaluated high frequency US and five of these reported healing at 7 - 8 weeks. Significantly more patients healed with US than without it at 7 - 8 weeks (pooled RR 1.4, 95% CI 1.0 to 1.96), but later assessments at 12 weeks showed the increased risk of healing with US was no longer statistically significant (pooled RR 1.47, 95% CI 0.99 to 2.20). One poor-quality study of high-frequency US found no evidence of an effect on healing after three weeks' treatment.Two trials evaluated low frequency US and reported healing at different time points. Both trials reported no evidence of a difference in the proportion of ulcers healed with US compared with no US: both were significantly underpowered. AUTHORS' CONCLUSIONS: The trials evaluating US for venous leg ulcers are small, poor-quality and heterogeneous. There is no reliable evidence that US hastens healing of venous ulcers. There is a small amount of weak evidence of increased healing with US, but this requires confirmation in larger, high-quality RCTs. There is no evidence of a benefit associated with low frequency US.

Antibiotics and antiseptics for venous leg ulcers.

BACKGROUND: Venous leg ulcers are a type of chronic wound affecting up to 1% of adults in developed countries at some point during their lives. Many of these wounds are colonised by bacteria or show signs of clinical infection. The presence of infection may delay ulcer healing. There are two main strategies used to prevent and treat clinical infection in venous leg ulcers: systemic antibiotics and topical antibiotics or antiseptics. OBJECTIVES: The objective of the review is to determine the effects of systemic antibiotics, topical antibiotics and antiseptics on the healing of venous ulcers. SEARCH STRATEGY: For the update of this review we searched the Cochrane Wounds Group Specialised Register (searched 24/09/09); The Cochrane Central Register of Controlled Trials (CENTRAL) - The Cochrane Library 2009 Issue 3; Ovid MEDLINE - 1950 to September Week 3 2009; Ovid EMBASE - 1980 to 2009 Week 38; and EBSCO CINAHL - 1982 to September Week 3 2009. No language or publication date restrictions were applied. SELECTION CRITERIA: Randomised controlled trials recruiting people with venous leg ulceration and evaluating at least one systemic antibiotic, topical antibiotic or topical antiseptic that reported an objective assessment of wound healing (e.g. time to complete healing, frequency of complete healing, change in ulcer surface area) were eligible for inclusion. Selection decisions were made by two authors working independently. DATA COLLECTION AND ANALYSIS: Information on the characteristics of participants, interventions and outcomes were recorded on a standardised data extraction form. In addition, aspects of trial methods were extracted, including randomisation, allocation concealment, blinding of participants and outcome assessors, incomplete outcome data and study group comparability at baseline. Data extraction and validity assessment were conducted by one author and checked by a second. MAIN RESULTS: Twenty five trials reporting 32 comparisons were identified. Five trials evaluated systemic antibiotics; the remainder evaluated topical preparations: cadexomer iodine (10 trials); povidone iodine (5 trials); peroxide-based preparations (3 trials); ethacridine lactate (1 trial); mupirocin (1 trial); and chlorhexidine (1 trial). For the systemic antibiotics, the only comparison where a statistically significant between-group difference was detected was that in favour of the antihelminthic levamisole when compared with placebo. This trial, in common with the other evaluations of systemic antibiotics, was small and so the observed effect could have occurred by chance or been due to baseline imbalances in prognostic factors. For topical preparations, there is some evidence to suggest that cadexomer iodine generates higher healing rates than standard care. One study showed a statistically significant result in favour of cadexomer iodine when compared with standard care (not involving compression) in the frequency of complete healing at six weeks (RR 2.29, 95% CI 1.10 to 4.74). The intervention regimen used was intensive, involving daily dressing changes, and so these findings may not be generalisable to most everyday clinical settings. When cadexomer iodine was compared with standard care with all patients receiving compression, the pooled estimate from two trials for frequency of complete healing at 4 to 6 weeks indicated significantly higher healing rates for cadexomer iodine (RR 6.72, 95% CI 1.56 to 28.95). Surrogate healing outcomes such as change in ulcer surface area and daily or weekly healing rate showed favourable results for cadexomer iodine, peroxide-based preparations and ethacridine lactate in some studies. These surrogate outcomes may not be valid proxies for complete healing of the wound. Most of the trials were small and many had methodological problems such as poor baseline comparability between groups, failure to use (or report) true randomisation, adequate allocation concealment, blinded outcome assessment and analysis by intention-to-treat. AUTHORS' CONCLUSIONS: At present, there is no evidence to support the routine use of systemic antibiotics to promote healing in venous leg ulcers. However, the lack of reliable evidence means that it is not possible to recommend the discontinuation of any of the agents reviewed. In terms of topical preparations, there is some evidence to support the use of cadexomer iodine. Further good quality research is required before definitive conclusions can be made about the effectiveness of systemic antibiotics and topical preparations such as povidone iodine, peroxide-based preparations, ethacridine lactate, mupirocin and chlorhexidine in healing venous leg ulceration. In light of the increasing problem of bacterial resistance to antibiotics, current prescribing guidelines recommend that antibacterial preparations should only be used in cases of clinical infection and not for bacterial colonisation.

Time matters: Point of care screening and streamlined linkage to care dramatically improves hepatitis C treatment uptake in prisoners in England.

BACKGROUND: In England, opt-out dry blood spot prison screening for HIV, hepatitis B and hepatitis C (HCV) has been introduced to scale-up access to care. Recent advances in point-of-care HCV diagnostics provide an opportunity to improve diagnosis and treatment uptake. We compared the retention along and time intervals between each aspect of the HCV care continuum for an alternative rapid point-of-care-testing and simplified treatment strategy with existing national opt-out HCV dry blood spot testing and treatment at a large remand prison in West London. METHODS: Between September 2017 and December 2018 universal opt-out dry blood spot HCV testing, clinical assessment and treatment uptake were recorded at Her Majesty's Prison Wormwood Scrubs. Outcomes were compared to a point-of-care-based (salivary Oraquick® anti-HCV screening and Xpert® HCV fingerstick viral load) screening and streamlined treatment pathway offered to all new arrivals to the HMP Wormwood Scrubs substance misuse unit, which ran in parallel to dry blood spot testing between September and December 2018. RESULTS: During the study period 2442 out of 5239 inmates (46.6%) underwent dry blood spot screening, resulting in 62 (2.6%) HCV RNA positive cases. Thirteen (21.3%) individuals commenced therapy and no viral relapse cases were observed to date. In comparison, 162 out of 181 (89.5%) inmates admitted to the substance misuse unit agreed to rapid point-of-care testing; 20 (12.3%) HCV RNA positive cases. Seventeen (85.0%) of eligible inmates commenced treatment. The median length of stay (90 vs 30 days), time to screening (6 vs 2 days), assessment (14 vs 3 days) and treatment (36 vs 1 day) were shorter for the rapid point-of-care screen-and-treat group. CONCLUSION: Current scaling-up of prison dry blood spot HCV screening and treatment in England is sub-optimal. In our setting, the cascade of care is time and resource sensitive and is greatly improved by the introduction of a simplified screen-and-treat strategy.