Background Chronic limb-threatening ischaemia with ischaemic pain and/or tissue loss. Objective To examine the clinical and cost-effectiveness of a vein bypass-first compared to a best endovascular treatment-first revascularisation strategy in preventing major amputation or death. Design Superiority, open, pragmatic, multicentre, phase III randomised trial. Setting Thirty-nine vascular surgery units in the United Kingdom, and one each in Sweden and Denmark. Participants Patients with chronic limb-threatening ischaemia due to atherosclerotic peripheral arterial disease who required an infra-popliteal revascularisation, with or without an additional more proximal infra-inguinal revascularisation procedure, to restore limb perfusion. Interventions A vein bypass-first or a best endovascular treatment-first infra-popliteal, with or without an additional more proximal infra-inguinal revascularisation strategy. Main outcome measures The primary outcome was amputation-free survival. Secondary outcomes included overall survival, major amputation, further revascularisation interventions, major adverse limb event, health-related quality of life and serious adverse events. Methods Participants were randomised to a vein bypass-first or a best endovascular treatment-first revascularisation strategy. The original sample size of 600 participants (247 events) was based on a hazard ratio of 0.66 with amputation-free survival rates of 0.72, 0.62, 0.53, 0.47 and 0.35 in years 1–5 in the best endovascular treatment-first group with 90% power and alpha at p = 0.05. The sample size was revised to an event-based approach as a result of increased follow-up time due to slower than anticipated recruitment rates. Participants were followed up for a minimum of 2 years. A cost-effectiveness analysis was employed to estimate differences in total hospital costs and amputation-free survival between the groups. Additionally, a cost–utility analysis was carried out and the total cost and quality-adjusted life-years, 2 and 3 years after randomisation were used. Results Between 22 July 2014 and 30 November 2020, 345 participants were randomised, 172 to vein bypass-first and 173 to best endovascular treatment-first. Non-amputation-free survival occurred in 108 (63%) of 172 patients in the vein bypass-first group and 92 (53%) of 173 patients in the best endovascular treatment-first group [adjusted hazard ratio 1.35 (95% confidence interval 1.02 to 1.80); p = 0.037]. Ninety-one (53%) of 172 patients in the vein bypass-first group and 77 (45%) of 173 patients in the best endovascular treatment-first group died [adjusted hazard ratio 1.37 (95% confidence interval 1.00 to 1.87)]. Over follow-up, the economic evaluation discounted results showed that best endovascular treatment-first was associated with £1690 less hospital costs compared to vein bypass-first. The cost utility analysis showed that compared to vein bypass-first, best endovascular treatment-first was associated with £224 and £2233 less discounted hospital costs and 0.016 and 0.085 discounted quality-adjusted life-year gain after 2 and 3 years from randomisation. Limitations Recruiting patients to the Bypass versus Angioplasty in Severe Ischaemia of the Leg Trial-2 trial was difficult and the target number of events was not achieved. Conclusions A best endovascular treatment-first revascularisation strategy was associated with better amputation-free survival, which was largely driven by fewer deaths. Overall, the economic evaluation results suggest that best endovascular treatment-first dominates vein bypass-first in the cost-effectiveness analysis and cost–utility analysis as it was less costly and more effective than a vein bypass-first strategy. Future work The Bypass versus Angioplasty in Severe Ischaemia of the Leg Trial-2 investigators have a data sharing agreement with the BEst Surgical Therapy in patients with Chronic Limb threatening Ischaemia investigators. One output of this collaboration will be an individual patient data meta-analysis. Study registration Current Controlled Trials ISRCTN27728689. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/35/45) and is published in full in Health Technology Assessment ; Vol. 28, No. 65. See the NIHR Funding and Awards website for further award information.
Bacterial vaginosis (BV) is a common, embarrassing and distressing condition, with serious comorbidities. The VITA trial assessed the effectiveness of intravaginal lactic acid gel versus oral metronidazole for treating recurrent BV.
Methods
Open-label, multicentre, parallel group, randomised controlled trial. Women aged ≥16 years with history of BV within the past 2 years and current symptoms were recruited at one GP practice and 19 sexual health centres in the UK. Participants were randomised to 5ml intravaginal lactic acid gel or oral 400mg twice daily metronidazole tablets, for 7 days. The primary outcome was participant reported resolution of BV symptoms by the end of Week 2, with subsequent follow up over 6 months. Semi-structured interviews explored tolerability and acceptability of the study treatments.
Results
518 participants were randomised (259 to metronidazole, 259 to lactic acid gel). Primary outcome data were available for 204 (79%) participants allocated to metronidazole and 205 (79%) allocated to lactic acid gel. Resolution of BV at Week 2 occurred in 143 (70%) participants in the metronidazole arm versus 97 (47%) participants in the lactic acid gel arm (adjusted risk difference -23.2% (95% CI -32.3 to -14.0%). Symptom resolution with no subsequent recurrences over 6 months occurred in 23% of those who took metronidazole and 16% of those using lactic acid gel. Side effects were more common following metronidazole compared to lactic acid gel. Interviews revealed that many women preferred lactic acid gel despite perceiving antibiotics to be more effective.
Conclusion
Metronidazole is more effective than lactic acid gel in achieving short term resolution of BV symptoms but recurrence is common following both treatments. Lactic acid is associated with fewer reported side effects and is preferred by many women despite its lower efficacy.
Funding
UK National Institute for Health Research Health Technology Assessment.
ABSTRACT Objectives Men who have sex with men (MSM) are disproportionately affected by sexually transmitted infections (STIs). Partner notification (PN) to identify, test and treat sex partners of MSM with bacterial STIs is challenging because MSM often report larger numbers of sex partners and a higher proportion of one-off partners who may be difficult to engage. However, one-off partners contribute disproportionately to onward transmission. Economic research on PN has typically focused on heterosexual people and evidence of effectiveness of PN in MSM is scant. We conducted a systematic review of economic studies of PN interventions in MSM to inform the development of a novel PN intervention for MSM with one-off partners. Method Six electronic databases were searched up to June 2020. Cost studies and full economic evaluations, which focused on PN and/or testing and treatment (in the context of PN) of sex partners of MSM with STIs, and/or HIV, were included. A two-stage categorisation process was used for study selection and a narrative synthesis was reported. Results Twenty-six studies of a possible 1909 met the selection criteria. Sixteen focused on MSM but only three of these were on PN. Few studies reported on patients’ characteristics and settings. Most studies were cost-utility analyses with outcomes reported as quality-adjusted life years (QALYs) which were derived from studies on heterosexual people. Conclusions None of the identified studies specifically addressed cost-effectiveness of PN in MSM. The few studies identified as potentially relevant relied on costs and QALYs data from studies in heterosexual people, which may be inappropriate given the different patterns of sexual partnerships reported by these two groups. The lack of evidence on efficient PN approaches for MSM, a group with a high burden of infection, supports the need for new interventions tailored to the needs and preferences of MSM with parallel economic evaluation.
Atrial fibrillation (AF) is a major and increasing burden on health services. This study aimed to evaluate the cost-effectiveness of digoxin versus beta-blockers for heart rate control in patients with permanent AF and symptoms of heart failure. RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) was a randomised, open-label, blinded, endpoint trial embedded in the UK National Health Service (NHS) to directly compare low-dose digoxin with beta-blockers (ClinicalTrials.gov: NCT02391337). A trial-based cost-utility analysis was performed from a healthcare perspective over 12 months. Resource use in primary and secondary healthcare services, medications and patient-reported quality of life were prospectively collected to estimate differences in costs and quality-adjusted life years (QALYs). RATE-AF randomised 160 patients with mean age of 76 (SD 8) years and 46% women, of which 149 patients (n=73 digoxin, n=76 beta blockers) had complete data and survived to 12-month follow-up. Treatment with digoxin was significantly less costly, with a mean saving of £530.41 per patient per year (95% CI -£848.06 to -£249.38, p=0.001). This was principally due to substantially lower rates of adverse events, with less primary and secondary healthcare utilisation compared with beta-blocker therapy. There was no significant difference in QALYs (0.013; 95% CI -0.033 to 0.052, p=0.56). At the £20 000 per-QALY willingness to pay threshold, the probability of digoxin being cost-effective compared with beta-blockers was 94%, with potential annual savings to the NHS of £102 million/year (95% CI £48 million to £164 million saving, p=0.001). Digoxin is a less costly option when compared with beta-blockers for control of heart rate in suitable patients with permanent AF, with larger cost-effectiveness studies warranted to advise on national and global policy-making. NCT02391337, EudraCT 2015-005043-13.
Abstract Background and Aims Tobacco consumption and its associated adverse outcomes remain major public health issues, particularly in low‐ and middle‐income countries. This systematic review aimed to identify and critically assess full economic evaluations for tobacco control interventions in low‐ and middle‐income countries. Methods Electronic databases, including EMBASE, MEDLINE and PsycINFO and the grey literature, were searched using terms such as ‘tobacco’, ‘economic evaluation’ and ‘smoking’ from 1994 to 2020. Study quality was assessed using the Consensus Health Economic Criteria and the Philips checklist. Studies were included which were full economic evaluations of tobacco control interventions in low‐ and middle‐income settings. Reviews, commentaries, conference proceedings and abstracts were excluded. Study selection and quality assessment were conducted by two reviewers independently. A narrative synthesis was conducted to synthesize the findings of the studies. Results This review identified 20 studies for inclusion. The studies evaluated a wide range of interventions, including tax increase, nicotine replacement therapy (nicotine patch/gum) and financial incentives. Overall, 12 interventions were reported to be cost‐effective, especially tax increases for tobacco consumption and cessation counselling. There were considerable limitations regarding data sources (e.g. using cost data from other countries or assumptions due to the lack of local data) and the model structure; sensitivity analyses were inadequately described in many studies; and there were issues around the transferability of results to other settings. Additionally, the affordability of the interventions was only discussed in two studies. Conclusions There are few high‐quality studies of the cost‐effectiveness of tobacco use control interventions in low‐ and middle‐income countries. The methodological limitations of the existing literatures could affect the generalizability of the findings.
Background Surgical site infection (SSI) is a worldwide problem which has morbidity, mortality and financial consequences. The incidence rate of SSI is high in Low- and Middle-Income countries (LMICs) compared to high income countries, and the costly surgical complication can raise the potential risk of financial catastrophe. Objective The aim of the study is to critically appraise studies on the cost of SSI in a range of LMIC studies and compare these estimates with a reference standard of high income European studies who have explored similar SSI costs. Methods A systematic review was undertaken using searches of two electronic databases, EMBASE and MEDLINE In-Process & Other Non-Indexed Citations, up to February 2019. Study characteristics, comparator group, methods and results were extracted by using a standard template. Results Studies from 15 LMIC and 16 European countries were identified and reviewed in full. The additional cost of SSI range (presented in 2017 international dollars) was similar in the LMIC ($174—$29,610) and European countries ($21—$34,000). Huge study design heterogeneity was encountered across the two settings. Discussion SSIs were revealed to have a significant cost burden in both LMICs and High Income Countries in Europe. The magnitude of the costs depends on the SSI definition used, severity of SSI, patient population, choice of comparator, hospital setting, and cost items included. Differences in study design affected the comparability across studies. There is need for multicentre studies with standardized data collection methods to capture relevant costs and consequences of the infection across income settings.
Bacterial vaginosis is a common and distressing condition associated with serious comorbidities. Antibiotic treatment is usually clinically effective in the short term, but recurrence is common and side effects can occur.The objective is to assess whether or not intravaginal lactic acid gel is clinically effective and cost-effective for treating recurrent bacterial vaginosis compared with oral metronidazole (Flagyl, Sanofi).This was an open-label, multicentre, parallel-arm, randomised (1 : 1) controlled trial.This took place in one general practice and 19 sexual health centres in the UK.Women aged ≥ 16 years with bacterial vaginosis symptoms and one or more episode(s) within the past 2 years took part.The interventions were 5 ml of intravaginal lactic acid gel taken once daily for 7 days (intervention) or 400-mg oral metronidazole tablets taken twice daily for 7 days (control).The primary outcome was the resolution of bacterial vaginosis symptoms 14 days after randomisation. The secondary outcomes were time to first recurrence of symptoms; number of recurrences and treatment courses over 6 months; microbiological resolution on microscopy of vaginal smears at week 2; time to resolution of symptoms; tolerability, adherence and acceptability of the treatment; prevalence of concurrent sexually transmitted infections; quality of life; and cost-effectiveness.Recruitment stopped prior to reaching the target of 1900 participants on recommendation from the Data Monitoring Committee and Trial Steering Committee after a planned review of the results indicated that the research question had been answered. Overall, 518 participants were randomised and primary outcome data were available for 409 participants (79%; 204 in the metronidazole arm, 205 in the lactic acid gel arm). Participant-reported symptom resolution at week 2 was higher with metronidazole (143/204; 70%) than with lactic acid gel (97/205; 47%) (adjusted risk difference -23.2%, 95% confidence interval -32.3% to -14.0%). Recurrence in 6 months in a subset of participants who had initial resolution and were available for follow-up was similar across arms (metronidazole arm: 51/72, 71%; lactic acid gel arm: 32/46, 70%). A higher incidence of some side effects was reported with metronidazole than with lactic acid gel (nausea 32% vs. 8%; taste changes 18% vs. 1%; diarrhoea 20% vs. 6%, respectively). At week 2, the average cost per participant with resolved symptoms was £86.94 (metronidazole), compared with £147.00 (lactic acid gel). Some participants preferred using lactic acid gel even if they perceived it to be less effective than metronidazole.Loss to follow-up for collection of the primary outcome data was 21% and was similar in both arms. There is a risk of bias owing to missing outcome data at 3 and 6 months post treatment.A higher initial response was seen with metronidazole than with lactic acid gel, but subsequent treatment failure was common with both. Lactic acid gel was less cost-effective than metronidazole. In general, women disliked taking repeated courses of metronidazole and preferred lactic acid gel, even when they were aware that it was less likely to provide symptom resolution. In the absence of effective curative therapy, further evaluation of non-antibiotic treatments to control the symptoms of recurrent bacterial vaginosis is required to improve quality of life for these patients. Further microbiological analysis of vaginal samples would be useful to identify additional factors affecting response to treatment.Current Controlled Trials ISRCTN14161293.This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 2. See the NIHR Journals Library website for further project information.Bacterial vaginosis is a common cause of unpleasant vaginal discharge that is caused by an imbalance of vaginal bacteria. The usual treatment is an antibiotic called metronidazole (Flagyl, Sanofi). Although this generally works in the short term, symptoms often return, leading to the repeated use of antibiotics; this can cause side effects as well as increase the risk of antibiotic resistance. Lactic acid gel might be an alternative treatment, but previous studies have not confirmed how clinically effective it is. We wanted to find out if lactic acid gel was better than metronidazole for treating recurrent bacterial vaginosis. Women with typical symptoms and a history of bacterial vaginosis who were taking part in our trial were selected randomly to receive either 7 days of treatment with lactic acid gel inserted into the vagina once per day or 7 days of treatment with metronidazole tablets taken by mouth twice per day. Overall, 518 women took part in the trial. We originally intended to recruit 1900 women but the trial was stopped early because a planned review of the data showed which treatment was better. Most of the women took all of their treatment and 70% reported that symptoms had cleared 2 weeks after taking metronidazole, compared with 47% after using lactic acid gel. Less than half of the women stayed in the trial for the full 6 months; however, the data suggested that the majority of those whose symptoms cleared within 2 weeks with either treatment had symptoms return over the next 6 months. More side effects were reported for metronidazole than for lactic acid gel: nausea 32% compared with 8%, taste changes 18% compared with 1%, and diarrhoea 20% compared with 6%, respectively. Despite thinking that it was less effective, women preferred lactic acid gel because it avoided the need to take an antibiotic and had a soothing effect. The cost-effectiveness analysis found that lactic acid gel was less effective than metronidazole in clearing symptoms by 2 weeks and that the average costs for women whose symptoms resolved were higher (£86.94 with metronidazole vs. £147.00 with lactic acid gel).
Bacterial vaginosis is a common and distressing condition for women. Short-term antibiotic treatment is usually clinically effective, but recurrence is common. We assessed the effectiveness of intravaginal lactic acid gel versus oral metronidazole for treating recurrent bacterial vaginosis.
Abstract Background: Bacterial vaginosis is a common and distressing condition for women. Short-term antibiotic treatment is usually clinically effective, but recurrence is common. We assessed the effectiveness of intravaginal lactic acid gel versus oral metronidazole for treating recurrent bacterial vaginosis. Methods: We undertook an open-label, multicentre, parallel group, randomised controlled trial in nineteen UK sexual health clinics and a university health centre. Women aged ≥16 years, with current bacterial vaginosis symptoms and a preceding history of bacterial vaginosis, were randomised in a 1:1 ratio using a web-based minimisation algorithm, to 400mg twice daily oral metronidazole tablets or 5ml once daily intravaginal lactic acid gel, for 7 days. Masking of participants was not possible. The primary outcome was participant-reported resolution of symptoms within 2 weeks. Secondary outcomes included time to first recurrence of symptoms, number of recurrences and repeat treatments over 6 months and side effects. Results: 518 participants were randomised before the trial was advised to stop recruiting by the Data Monitoring Committee. Primary outcome data were available for 79% (204/259) allocated to metronidazole and 79% (205/259) allocated to lactic acid gel. Resolution of bacterial vaginosis symptoms within 2 weeks was reported in 70% (143/204) receiving metronidazole versus 47% (97/205) receiving lactic acid gel (adjusted risk difference -23·2%; 95% confidence interval -32.3 to -14·0%). In those participants who had initial resolution and for whom 6 month data were available, 51 of 72 (71%) women in the metronidazole group and 32 of 46 women (70%) in the lactic acid gel group had recurrence of symptoms, with median times to first recurrence of 92 and 126 days, respectively. Reported side effects were more common following metronidazole than lactic acid gel (nausea 32% vs. 8%; taste changes 18% vs. 1%; diarrhoea 20% vs. 6%, respectively). Conclusions: Metronidazole was more effective than lactic acid gel for short-term resolution of bacterial vaginosis symptoms, but recurrence is common following both treatments. Lactic acid gel was associated with fewer reported side effects. Trial registration : ISRCTN14161293, prospectively registered on 18 th September 2017. https://doi.org/10.1186/ISRCTN14161293.
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