A randomised controlled trial of compression therapies for the treatment of venous leg ulcers (VenUS 6): study protocol for a pragmatic, multicentre, parallel-group, three-arm randomised controlled trial.

BACKGROUND: Venous leg ulcer(s) are common, recurring, open wounds on the lower leg, resulting from diseased or damaged leg veins impairing blood flow. Wound healing is the primary treatment aim for venous leg ulceration, alongside the management of pain, wound exudate and infection. Full (high) compression therapy delivering 40 mmHg of pressure at the ankle is the recommended first-line treatment for venous leg ulcers. There are several different forms of compression therapy available including wraps, two-layer hosiery, and two-layer or four-layer bandages. There is good evidence for the clinical and cost-effectiveness of four-layer bandage and two-layer hosiery but more limited evidence for other treatments (two-layer bandage and compression wraps). Robust evidence is required to compare clinical and cost-effectiveness of these and to investigate which is the best compression treatment for reducing time to healing of venous leg ulcers whilst offering value for money. VenUS 6 will therefore investigate the clinical and cost-effectiveness of evidence-based compression, two-layer bandage and compression wraps for time to healing of venous leg ulcers. METHODS: VenUS 6 is a pragmatic, multi-centre, three-arm, parallel-group, randomised controlled trial. Adult patients with a venous leg ulcer will be randomised to receive (1) compression wraps, (2) two-layer bandage or (3) evidence-based compression (two-layer hosiery or four-layer bandage). Participants will be followed up for between 4 and 12 months. The primary outcome will be time to healing (full epithelial cover in the absence of a scab) in days since randomisation. Secondary outcomes will include key clinical events (e.g. healing of the reference leg, ulcer recurrence, ulcer/skin deterioration, amputation, admission/discharge, surgery to close/remove incompetent superficial veins, infection or death), treatment changes, adherence and ease of use, ulcer related pain, health-related quality of life and resource use. DISCUSSION: VenUS 6 will provide robust evidence on the clinical and cost-effectiveness of the different forms of compression therapies for venous leg ulceration. VenUS 6 opened to recruitment in January 2021 and is currently recruiting across 30 participating centres. TRIAL REGISTRATION: ISRCTN67321719 . Prospectively registered on 14 September 2020.

Patients with surgical wounds healing by secondary intention: A prospective, cohort study.

BACKGROUND: Surgical wounds healing by secondary intention can be difficult and costly to manage and are profoundly under researched. This prospective inception, cohort study aimed to derive a better understanding of surgical wounds healing by secondary intention and to facilitate the design of future research investigating effective treatments. OBJECTIVES: To investigate the clinical characteristics of patients with surgical wounds healing by secondary intention and the surgeries that preceded their wounds; to clearly delineate the clinical outcomes of these patients, specifically focusing on time to wound healing and its determinants; to explore the types of treatments for surgical wounds healing by secondary intention; and to assess the impact surgical wounds healing by secondary intention have on patients' quality of life. DESIGN: Prospective, inception cohort study. SETTING: Acute and community settings in eight sites across two large centres in the United Kingdom (Hull and Leeds, UK). METHODS: Patients with a surgical wounds healing by secondary intention (an open wound, <3 weeks' duration, resulting from surgery), were recruited and followed up for at least 12 months. Key outcome events included: time to healing; treatment type; infection; hospital re-admission and further procedures; health-related quality of life and pain. RESULTS: In total, 393 patients were recruited. Common co-morbidities were cardiovascular disease (38%), diabetes (26%) and peripheral vascular disease (14.5%). Baseline median SWHSI area was 6 cm2 (range 0.01-1200). Abdominal (n = 132), foot (n = 59), leg (n = 58) and peri-anal (n = 34) wounds were common. The majority of wounds (236, 60.1%) were intentionally left open following surgery; the remainder were mostly dehisced wounds. Healing was observed in 320 (81.4%) wounds with a median time to healing of 86 days (95% CI: 75-130). Factors associated with delayed healing included wound infection at any point and baseline wound area above the median. Health-related quality of life scores were low at baseline but improved with time and healing. CONCLUSIONS: This is the first inception cohort study in patients with surgical wounds healing by secondary intention. Patient characteristics have been clearly defined, with prolonged healing times and adverse events being common impacting on patient's health-related quality of life. Areas for, and factors crucial to the design of, future research have been identified.

High-throughput, non-invasive prenatal testing for fetal Rhesus D genotype to guide antenatal prophylaxis with anti-D immunoglobulin: a cost-effectiveness analysis.

OBJECTIVE: To evaluate the cost-effectiveness of high-throughput, non-invasive prenatal testing (HT-NIPT) for fetal Rhesus D (RhD) genotype to guide antenatal prophylaxis with anti-D immunoglobulin compared with routine antenatal anti-D immunoglobulin prophylaxis (RAADP). DESIGN: Cost-effectiveness decision-analytic modelling. SETTING: Primary care. PARTICIPANTS: A simulated population of 100 000 RhD-negative women not known to be sensitised to the RhD antigen. METHODS: A decision tree model was used to characterise the antenatal care pathway in England and the long-term consequences of sensitisation events. The diagnostic accuracy of HT-NIPT was derived from a systematic review and bivariate meta-analysis; estimates of other inputs were derived from relevant literature sources and databases. Women in whom the HT-NIPT was positive or inconclusive continued to receive RAADP, whereas women with a negative result received none. Five alternative strategies in which the use of HT-NIPT may affect the existing postpartum care pathway were considered. MAIN OUTCOME MEASURES: Costs expressed in 2015GBP and impact on health outcomes expressed in terms of quality-adjusted life-years over a lifetime. RESULTS: The results suggested that HT-NIPT appears cost saving but also less effective than current practice, irrespective of the postpartum strategy evaluated. A postpartum strategy in which inconclusive test results are distinguished from positive results performed best. HT-NIPT is only cost-effective when the overall test cost is £26.60 or less. CONCLUSIONS: HT-NIPT would reduce unnecessary treatment with routine anti-D immunoglobulin and is cost saving when compared with current practice. The extent of any savings and cost-effectiveness is sensitive to the overall test cost. TWEETABLE ABSTRACT: HT-NIPT is cost saving compared with providing anti-D to all RhD-negative pregnant women.

Topotecan for the treatment of recurrent and stage IVB carcinoma of the cervix.

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of topotecan in combination with cisplatin for the treatment of recurrent and stage IVB carcinoma of the cervix, in accordance with the licensed indication, based upon the evidence submission from the manufacturer to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The outcomes measured were overall survival, progression-free survival, response rates, adverse effects of treatment, health-related quality of life (HRQoL) and quality-adjusted life-years (QALYs) gained. The manufacturer stated that topotecan plus cisplatin is the only combination regimen to date to have demonstrated a statistically significant survival advantage compared to cisplatin monotherapy in the licensed population. The clinical evidence came from three clinical trials comparing topotecan plus cisplatin with cisplatin monotherapy (GOG-0179), topotecan plus cisplatin with paclitaxel plus cisplatin (GOG-0169), and four cisplatin-based combination therapies: topotecan plus cisplatin, paclitaxel plus cisplatin, gemcitabine plus cisplatin, and vinorelbine plus cisplatin (GOG-0204). Results from GOG-0179 showed greater median overall survival with topotecan plus cisplatin than with cisplatin monotherapy: 9.4 months versus 6.5 months. Similar results were also reported for median progression-free survival. Response rates also showed an advantage with topotecan plus cisplatin compared with cisplatin monotherapy. The response rates in patients receiving cisplatin monotherapy were very low, but the potential reasons for this were not discussed in the manufacturer's submission. Patients receiving topotecan plus cisplatin experienced a greater number of adverse events and the ERG was concerned with some of the assumptions related to HRQoL. In the base-case direct comparison, the incremental cost-effectiveness ratio (ICER) of topotecan plus cisplatin versus cisplatin monotherapy was 17,974 pounds per QALY in the main licensed population, 10,928 pounds per QALY in the cisplatin-naive population (including stage IVB patients) and 32,463 pounds per QALY in sustained cisplatin-free interval patients. In response to the point for clarification raised by the ERG, the manufacturer submitted a revised indirect comparison incorporating HRQoL and a longer time horizon. Where the hazard ratio derived from GOG-0169 was employed, paclitaxel plus cisplatin was dominated by topotecan plus cisplatin, but, where the hazard ratio from GOG-0204 was adopted, paclitaxel plus cisplatin was found to have an ICER of 13,260 pounds per QALY versus topotecan plus cisplatin. At present there is a paucity of evidence available on the clinical effects of topotecan plus cisplatin and the effects of palliative treatment in general for women with advanced and recurrent carcinoma of the cervix. Further trials, or the implementation of registries, are required to establish the efficacy and safety of topotecan plus cisplatin. The guidance issued by NICE on 28 October 2009 as a result of the STA states that topotecan in combination with cisplatin is recommended as a treatment option for women with recurrent or stage IVB cervical cancer, only if they have not previously received cisplatin. Women who have previously received cisplatin and are currently being treated with topotecan in combination with cisplatin for the treatment of cervical cancer should have the option to continue therapy until they and their clinicians consider it appropriate to stop.