Long acting progestogens versus combined oral contraceptive pill for preventing recurrence of endometriosis related pain: the PRE-EMPT pragmatic, parallel group, open label, randomised controlled trial.

OBJECTIVES: To evaluate the clinical effectiveness of long acting progestogens compared with the combined oral contraceptive pill in preventing recurrence of endometriosis related pain. DESIGN: The PRE-EMPT (preventing recurrence of endometriosis) pragmatic, parallel group, open label, randomised controlled trial. SETTING: 34 UK hospitals. PARTICIPANTS: 405 women of reproductive age undergoing conservative surgery for endometriosis. INTERVENTIONS: Participants were randomised in a 1:1 ratio using a secure internet facility to a long acting progestogen (depot medroxyprogesterone acetate or levonorgestrel releasing intrauterine system) or the combined oral contraceptive pill. MAIN OUTCOME MEASURES: The primary outcome was pain measured three years after randomisation using the pain domain of the Endometriosis Health Profile 30 (EHP-30) questionnaire. Secondary outcomes (evaluated at six months, one, two, and three years) included the four core and six modular domains of the EHP-30, and treatment failure (further therapeutic surgery or second line medical treatment). RESULTS: 405 women were randomised to receive a long acting progestogen (n=205) or combined oral contraceptive pill (n=200). At three years, there was no difference in pain scores between the groups (adjusted mean difference -0.8, 95% confidence interval -5.7 to 4.2, P=0.76), which had improved by around 40% in both groups compared with preoperative values (an average of 24 and 23 points for long acting progestogen and combined oral contraceptive pill groups, respectively). Most of the other domains of the EHP-30 also showed improvement at all time points compared with preoperative scores, without evidence of any differences between groups. Women randomised to a long acting progestogen underwent fewer surgical procedures or second line treatments compared with those randomised to the combined oral contraceptive pill group (73 v 97; hazard ratio 0.67, 95% confidence interval 0.44 to 1.00). CONCLUSIONS: Postoperative prescription of a long acting progestogen or the combined oral contraceptive pill results in similar levels of improvement in endometriosis related pain at three years, with both groups showing around a 40% improvement compared with preoperative levels. While women can be reassured that both options are effective, the reduced risk of repeat surgery for endometriosis and hysterectomy might make long acting reversible progestogens preferable for some. TRIAL REGISTRATION: ISRCTN registry ISRCTN97865475.

Healthcare resource utilisation and economic burden attributable to back pain in primary care: A matched case-control study in the United Kingdom.

Objective: Incremental healthcare costs attributed to back pain, and characterisation by patient and clinical factors have rarely been documented. This study aimed to assess annual healthcare resource utilisation and costs associated with back pain in primary care. Methods: Using the IQVIA Medical Research Data (IMRD), patients with back pain were identified (study period: 01 January 2006 to 31 December 2015) using diagnostic records and analgesics prescriptions (n = 133,341), and propensity score matched 1:1 to patients without back pain. The annual incremental costs of back pain associated with consultations and prescriptions were estimated and extrapolated to a national level. Sensitivity analysis was conducted by restricting the study population to the most recent diagnosis of back pain. Variations in cost were assessed stratified by gender, age-groups, deprivation, and comorbidity categories. Results: The mean age was 57 years, and 62% were females in both the case and control groups. The total incremental healthcare costs associated with back pain was £32.5 million in 2015 (£35.9 million in 2020), with per-patient cost of £244 (£265 in 2020) per year. On a national level, this translated to an estimated £3.2 billion (£3.5 billion in 2020). Eighty percent of the costs were attributed to consultations; and female gender, older age, higher deprivation, and higher comorbidity were all associated with increased mean healthcare costs of patients with back pain. Conclusion: Our findings confirm the substantial healthcare costs attributed to back pain, even with primacy care costs only. The data also revealed significant cost variations across socio-demographic and clinical factors.

Erratum to "Exploring the cost-effectiveness of high versus low perioperative fraction of inspired oxygen in the prevention of surgical site infections among abdominal surgery patients in three low- and middle-income countries" [BJA Open 7 (2023) 100207].

[This corrects the article DOI: 10.1016/j.bjao.2023.100207.].

Erratum to 'Exploring the cost-effectiveness of high versus low perioperative fraction of inspired oxygen in the prevention of surgical site infections among abdominal surgery patients in three low- and middle-income countries' [BJA Open 7 (2023) 100207].

[This corrects the article DOI: 10.1016/j.bjao.2023.100207.].

Protocol for a multicentre randomised controlled trial of STeroid Administration Routes For Idiopathic Sudden sensorineural Hearing loss: The STARFISH trial.

Idiopathic sudden sensorineural hearing loss (ISSNHL) is the rapid onset of reduced hearing due to loss of function of the inner ear or hearing nerve of unknown aetiology. Evidence supports improved hearing recovery with early steroid treatment, via oral, intravenous, intratympanic or a combination of routes. The STARFISH trial aims to identify the most clinically and cost-effective route of administration of steroids as first-line treatment for ISSNHL. STARFISH is a pragmatic, multicentre, assessor-blinded, three-arm intervention, superiority randomised controlled trial (1:1:1) with an internal pilot (ISRCTN10535105, IRAS 1004878). 525 participants with ISSNHL will be recruited from approximately 75 UK Ear, Nose and Throat units. STARFISH will recruit adults with sensorineural hearing loss averaging 30dBHL or greater across three contiguous frequencies (confirmed via pure tone audiogram), with onset over a ≤3-day period, within four weeks of randomisation. Participants will be randomised to 1) oral prednisolone 1mg/Kg/day up to 60mg/day for 7 days; 2) intratympanic dexamethasone: three intratympanic injections 3.3mg/ml or 3.8mg/ml spaced 7±2 days apart; or 3) combined oral and intratympanic steroids. The primary outcome will be absolute improvement in pure tone audiogram average at 12-weeks following randomisation (0.5, 1.0, 2.0 and 4.0kHz). Secondary outcomes at 6 and 12 weeks will include: Speech, Spatial and Qualities of hearing scale, high frequency pure tone average thresholds (4.0, 6.0 and 8.0kHz), Arthur Boothroyd speech test, Vestibular Rehabilitation Benefit Questionnaire, Tinnitus Functional Index, adverse events and optional weekly online speech and pure tone hearing tests. A health economic assessment will be performed, and presented in terms of incremental cost effectiveness ratios, and cost per quality-adjusted life-year. Primary analyses will be by intention-to-treat. Oral prednisolone will be the reference. For the primary outcome, the difference between group means and 97.5% confidence intervals at each time-point will be estimated via a repeated measures mixed-effects linear regression model.

Trial of Selective Early Treatment of Patent Ductus Arteriosus with Ibuprofen.

BACKGROUND: The cyclooxygenase inhibitor ibuprofen may be used to treat patent ductus arteriosus (PDA) in preterm infants. Whether selective early treatment of large PDAs with ibuprofen would improve short-term outcomes is not known. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial evaluating early treatment (≤72 hours after birth) with ibuprofen for a large PDA (diameter of ≥1.5 mm with pulsatile flow) in extremely preterm infants (born between 23 weeks 0 days' and 28 weeks 6 days' gestation). The primary outcome was a composite of death or moderate or severe bronchopulmonary dysplasia evaluated at 36 weeks of postmenstrual age. RESULTS: A total of 326 infants were assigned to receive ibuprofen and 327 to receive placebo; 324 and 322, respectively, had data available for outcome analyses. A primary-outcome event occurred in 220 of 318 infants (69.2%) in the ibuprofen group and 202 of 318 infants (63.5%) in the placebo group (adjusted risk ratio, 1.09; 95% confidence interval [CI], 0.98 to 1.20; P = 0.10). A total of 44 of 323 infants (13.6%) in the ibuprofen group and 33 of 321 infants (10.3%) in the placebo group died (adjusted risk ratio, 1.32; 95% CI, 0.92 to 1.90). Among the infants who survived to 36 weeks of postmenstrual age, moderate or severe bronchopulmonary dysplasia occurred in 176 of 274 (64.2%) in the ibuprofen group and 169 of 285 (59.3%) in the placebo group (adjusted risk ratio, 1.09; 95% CI, 0.96 to 1.23). Two unforeseeable serious adverse events occurred that were possibly related to ibuprofen. CONCLUSIONS: The risk of death or moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age was not significantly lower among infants who received early treatment with ibuprofen than among those who received placebo. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Baby-OSCAR ISRCTN Registry number, ISRCTN84264977.).

Effectiveness and cost-effectiveness of Assets-based feeding help Before and After birth (ABA-feed) for improving breastfeeding initiation and continuation: protocol for a multicentre randomised controlled trial (Version 3.0).

INTRODUCTION: Breastfeeding has health benefits for infants and mothers, yet the UK has low rates with marked social inequalities. The Assets-based feeding help Before and After birth (ABA) feasibility study demonstrated the acceptability of a proactive, assets-based, woman-centred peer support intervention, inclusive of all feeding types, to mothers, peer supporters and maternity services. The ABA-feed study aims to assess the clinical and cost-effectiveness of the ABA-feed intervention compared with usual care in first-time mothers in a full trial. METHODS AND ANALYSIS: A multicentre randomised controlled trial with economic evaluation to explore clinical and cost-effectiveness, and embedded process evaluation to explore differences in implementation between sites. We aim to recruit 2730 primiparous women, regardless of feeding intention. Women will be recruited at 17 sites from antenatal clinics and various remote methods including social media and invitations from midwives and health visitors. Women will be randomised at a ratio of 1.43:1 to receive either ABA-feed intervention or usual care. A train the trainer model will be used to train local Infant Feeding Coordinators to train existing peer supporters to become 'infant feeding helpers' in the ABA-feed intervention. Infant feeding outcomes will be collected at 3 days, and 8, 16 and 24 weeks postbirth. The primary outcome will be any breastfeeding at 8 weeks postbirth. Secondary outcomes will include breastfeeding initiation, any and exclusive breastfeeding, formula feeding practices, anxiety, social support and healthcare utilisation. All analyses will be based on the intention-to-treat principle. ETHICS AND DISSEMINATION: The study protocol has been approved by the East of Scotland Research Ethics Committee. Trial results will be available through open-access publication in a peer-reviewed journal and presented at relevant meetings and conferences. TRIAL REGISTRATION NUMBER: ISRCTN17395671.

LAparoscopic Versus Abdominal hysterectomy (LAVA): protocol of a randomised controlled trial.

INTRODUCTION: There is uncertainty about the advantages and disadvantages of laparoscopic hysterectomy compared with abdominal hysterectomy, particularly the relative rate of complications of the two procedures. While uptake of laparoscopic hysterectomy has been slow, the situation is changing with greater familiarity, better training, better equipment and increased proficiency in the technique. Thus, a large, robust, multicentre randomised controlled trial (RCT) is needed to compare contemporary laparoscopic hysterectomy with abdominal hysterectomy to determine the safest and most cost-effective technique. METHODS AND ANALYSIS: A parallel, open, non-inferiority, multicentre, randomised controlled, expertise-based surgery trial with integrated health economic evaluation and an internal pilot with an embedded qualitative process evaluation. A within trial-based economic evaluation will explore the cost-effectiveness of laparoscopic hysterectomy compared with open abdominal hysterectomy. We will aim to recruit 3250 women requiring a hysterectomy for a benign gynaecological condition and who were suitable for either laparoscopic or open techniques. The primary outcome is major complications up to six completed weeks postsurgery and the key secondary outcome is time from surgery to resumption of usual activities using the personalised Patient-Reported Outcomes Measurement Information System Physical Function questionnaire. The principal outcome for the economic evaluation is to be cost per QALY at 12 months' postsurgery. A secondary analysis is to be undertaken to generate costs per major surgical complication avoided and costs per return to normal activities. ETHICS AND DISSEMINATION: The study was approved by the West Midlands-Edgbaston Research Ethics Committee, 18 February 2021 (Ethics ref: 21/WM/0019). REC approval for the protocol version 2.0 dated 2 February 2021 was issued on 18 February 2021.We will present the findings in national and international conferences. We will also aim to publish the findings in high impact peer-reviewed journals. We will disseminate the completed paper to the Department of Health, the Scientific Advisory Committees of the RCOG, the Royal College of Nurses (RCN) and the BSGE. TRIAL REGISTRATION NUMBER: ISRCTN14566195.

Expert opinion on a consensus-based checklist for the critical appraisal of cost-of-illness (COI) studies: qualitative interviews.

OBJECTIVES: This study explored experts' views on the development of a proposed checklist for cost-of-illness (COI) studies. It also investigated experts' perspectives on the use of COI studies and quality/critical appraisal tools used for COI studies as well as their experiences with the use of these tools. METHODS: Semi-structured, open-ended interviews were conducted with health economists and other experts working with COI studies and with experience of developing health economic guidelines or checklists. Participants were selected purposively using network and snowball sampling. A framework approach was applied for the thematic data analysis. Findings were reported narratively. RESULTS: Twenty-one experts from eleven different countries were interviewed. COI studies were found to be relevant to estimate the overall burden of a disease, to draw attention to disease areas, to understand different cost components, to explain cost variability, to inform decision making, and to provide input for full economic evaluations. Experts reported a lack of a standardized critical appraisal tool for COI studies. Their experience related predominantly to guidelines and checklists designed for full economic evaluations to review and assess COI studies. The following themes emerged when discussing the checklist: (i) the need for a critical appraisal tool, (ii) format and practicality, (iii) assessing the questions, (iv) addressing subjectivity, and (v) guidance requirements. CONCLUSIONS: The interviews provided relevant input for the development of a checklist for COI studies that could be used as a minimum standard and for international application. The interviews confirmed the important need for a checklist for the critical appraisal of COI studies.

A consensus-based checklist for the critical appraisal of cost-of-illness (COI) studies.

OBJECTIVES: To develop a consensus-based checklist that can be used as a minimum standard to appraise the comprehensiveness, transparency and consistency of cost-of-illness (COI) studies. This is important when, for instance, reviewing and assessing COI studies as part of a systematic review or when building an economic model. METHODS: The development process of the consensus-based checklist involved six steps: (i) a scoping review, (ii) an assessment and comparison of the different checklists and their questions, (iii) the development of a (preliminary) checklist, (iv) expert interviews, (v) the finalization of the checklist, and (vi) the development of guidance statements explaining each question. RESULTS: The result was a consensus-based checklist for the critical appraisal of COI studies, comprising seventeen main questions (and some additional subquestions) across three domains: (i) study characteristics; (ii) methodology and cost analysis; and (iii) results and reporting. Guidance statements were developed describing the purpose and meaning behind each question and listing examples of best practice. The following answer categories were suggested to be applied when answering the questions in the checklist: Yes, Partially, No, Not Applicable, or Unclear. CONCLUSIONS: The consensus-based checklist for COI studies is a first step toward standardizing the critical appraisal of COI studies and is one that could be considered a minimum standard. The checklist can help to improve comprehensiveness, transparency and consistency in COI studies, to address heterogeneity, and to enable better comparability of methodological approaches across international studies.

Randomized Trial of Early Detection and Treatment of Postpartum Hemorrhage.

BACKGROUND: Delays in the detection or treatment of postpartum hemorrhage can result in complications or death. A blood-collection drape can help provide objective, accurate, and early diagnosis of postpartum hemorrhage, and delayed or inconsistent use of effective interventions may be able to be addressed by a treatment bundle. METHODS: We conducted an international, cluster-randomized trial to assess a multicomponent clinical intervention for postpartum hemorrhage in patients having vaginal delivery. The intervention included a calibrated blood-collection drape for early detection of postpartum hemorrhage and a bundle of first-response treatments (uterine massage, oxytocic drugs, tranexamic acid, intravenous fluids, examination, and escalation), supported by an implementation strategy (intervention group). Hospitals in the control group provided usual care. The primary outcome was a composite of severe postpartum hemorrhage (blood loss, ≥1000 ml), laparotomy for bleeding, or maternal death from bleeding. Key secondary implementation outcomes were the detection of postpartum hemorrhage and adherence to the treatment bundle. RESULTS: A total of 80 secondary-level hospitals across Kenya, Nigeria, South Africa, and Tanzania, in which 210,132 patients underwent vaginal delivery, were randomly assigned to the intervention group or the usual-care group. Among hospitals and patients with data, a primary-outcome event occurred in 1.6% of the patients in the intervention group, as compared with 4.3% of those in the usual-care group (risk ratio, 0.40; 95% confidence interval [CI], 0.32 to 0.50; P<0.001). Postpartum hemorrhage was detected in 93.1% of the patients in the intervention group and in 51.1% of those in the usual-care group (rate ratio, 1.58; 95% CI, 1.41 to 1.76), and the treatment bundle was used in 91.2% and 19.4%, respectively (rate ratio, 4.94; 95% CI, 3.88 to 6.28). CONCLUSIONS: Early detection of postpartum hemorrhage and use of bundled treatment led to a lower risk of the primary outcome, a composite of severe postpartum hemorrhage, laparotomy for bleeding, or death from bleeding, than usual care among patients having vaginal delivery. (Funded by the Bill and Melinda Gates Foundation; E-MOTIVE ClinicalTrials.gov number, NCT04341662.).

Exploring the wider societal impacts of sexual health issues and interventions to build a framework for research and policy: a qualitative study based on in-depth semi-structured interviews with experts in OECD member countries.

OBJECTIVES: Sexual health is a complex public health challenge and can generate wide-ranging health, social and economic impacts both within and beyond the health sector (ie, intersectoral costs and benefits). Methods are needed to capture these intersectoral impacts in economic studies to optimally inform policy/decision-making. The objectives of this study were (1) to explore the different intersectoral costs and benefits associated with sexual health issues and interventions, (2) to categorise these into sectors and (3) to develop a preliminary framework to better understand these impacts and to guide future research and policy. DESIGN: A qualitative study based on in-depth semi-structured online interviews. SETTING: OECD (Organisation for Economic Co-operation and Development) member countries. PARTICIPANTS: Professionals with expertise in the field of sexual health including clinicians, medical practitioners, sexologists, researchers, professionals working for international governmental or non-governmental health (policy) organisations and professionals involved in implementation and/or evaluation of sexual health interventions/programmes. METHODS: Sampling of participants was undertaken purposively. We conducted in-depth semi-structured online interviews to allow for a systemic coverage of key topics and for new ideas to emerge. We applied a Framework approach for thematic data analysis. RESULTS: 28 experts were interviewed. Six themes emerged from the interviews: (1) Interconnections to other areas of health (ie, reproductive health, mental health), (2) Relationships and family, (3) Productivity and labour, (4) Education, (5) Criminal justice/sexual violence, (6) Housing, addiction and other sectors. The findings confirm that sexual health is complex and can generate wide-ranging impacts on other areas of health and other non-health sectors of society. CONCLUSION: These different sectors need to be considered when evaluating interventions and making policy decisions. The preliminary framework can help guide future research and policy/decision-making. Future research could explore additional sectors not covered in this study and expand the preliminary framework.

Are intersectoral costs considered in economic evaluations of interventions relating to sexually transmitted infections (STIs)? A systematic review.

BACKGROUND/OBJECTIVE: Sexually transmitted infections (STIs) not only have an impact on the health sector but also the private resources of those affected, their families and other sectors of society (i.e. labour, education). This study aimed to i) review and identify economic evaluations of interventions relating to STIs, which aimed to include a societal perspective; ii) analyse the intersectoral costs (i.e. costs broader than healthcare) included; iii) categorise these costs by sector; and iv) assess the impact of intersectoral costs on the overall study results. METHODS: Seven databases were searched: MEDLINE (PubMed), EMBASE (Ovid), Web of Science, CINAHL, PsycINFO, EconLit and NHS EED. Key search terms included terms for economic evaluation, STIs and specific infections. This review considered trial- and model-based economic evaluations conducted in an OECD member country. Studies were included that assessed intersectoral costs. Intersectoral costs were extracted and categorised by sector using Drummond's cost classification scheme (i.e. patient/family, productivity, costs in other sectors). A narrative synthesis was performed. RESULTS: Twenty-nine studies qualified for data extraction and narrative synthesis. Twenty-eight studies applied a societal perspective of which 8 additionally adopted a healthcare or payer perspective, or both. One study used a modified payer perspective. The following sectors were identified: patient/family, informal care, paid labour (productivity), non-paid opportunity costs, education, and consumption. Patient/family costs were captured in 11 studies and included patient time, travel expenses, out-of-pocket costs and premature burial costs. Informal caregiver support (non-family) and unpaid help by family/friends was captured in three studies. Paid labour losses were assessed in all but three studies. Three studies also captured the costs and inability to perform non-paid work. Educational costs and future non-health consumption costs were each captured in one study. The inclusion of intersectoral costs resulted in more favourable cost estimates. CONCLUSIONS: This systematic review suggests that economic evaluations of interventions relating to STIs that adopt a societal perspective tend to be limited in scope. There is an urgent need for economic evaluations to be more comprehensive in order to allow policy/decision-makers to make better-informed decisions.

Accelerated partner therapy contact tracing for people with chlamydia (LUSTRUM): a crossover cluster-randomised controlled trial.

BACKGROUND: Accelerated partner therapy has shown promise in improving contact tracing. We aimed to evaluate the effectiveness of accelerated partner therapy in addition to usual contact tracing compared with usual practice alone in heterosexual people with chlamydia, using a biological primary outcome measure. METHODS: We did a crossover cluster-randomised controlled trial in 17 sexual health clinics (clusters) across England and Scotland. Participants were heterosexual people aged 16 years or older with a positive Chlamydia trachomatis test result, or a clinical diagnosis of conditions for which presumptive chlamydia treatment and contact tracing are initially provided, and their sexual partners. We allocated phase order for clinics through random permutation within strata. In the control phase, participants received usual care (health-care professional advised the index patient to tell their sexual partner[s] to attend clinic for sexually transmitted infection screening and treatment). In the intervention phase, participants received usual care plus an offer of accelerated partner therapy (health-care professional assessed sexual partner[s] by telephone, then sent or gave the index patient antibiotics and sexually transmitted infection self-sampling kits for their sexual partner[s]). Each phase lasted 6 months, with a 2-week washout at crossover. The primary outcome was the proportion of index patients with a positive C trachomatis test result at 12-24 weeks after contact tracing consultation. Secondary outcomes included proportions and types of sexual partners treated. Analysis was done by intention-to-treat, fitting random effects logistic regression models. This trial is registered with the ISRCTN registry, 15996256. FINDINGS: Between Oct 24, 2018, and Nov 17, 2019, 1536 patients were enrolled in the intervention phase and 1724 were enrolled in the control phase. All clinics completed both phases. In total, 4807 sexual partners were reported, of whom 1636 (34%) were steady established partners. Overall, 293 (19%) of 1536 index patients chose accelerated partner therapy for a total of 305 partners, of whom 248 (81%) accepted. 666 (43%) of 1536 index patients in the intervention phase and 800 (46%) of 1724 in the control phase were tested for C trachomatis at 12-24 weeks after contact tracing consultation; 31 (4·7%) in the intervention phase and 53 (6·6%) in the control phase had a positive C trachomatis test result (adjusted odds ratio [OR] 0·66 [95% CI 0·41 to 1·04]; p=0·071; marginal absolute difference -2·2% [95% CI -4·7 to 0·3]). Among index patients with treatment status recorded, 775 (88·0%) of 881 patients in the intervention phase and 760 (84·6%) of 898 in the control phase had at least one treated sexual partner at 2-4 weeks after contact tracing consultation (adjusted OR 1·27 [95% CI 0·96 to 1·68]; p=0·10; marginal absolute difference 2·7% [95% CI -0·5 to 6·0]). No clinically significant harms were reported. INTERPRETATION: Although the evidence that the intervention reduces repeat infection was not conclusive, the trial results suggest that accelerated partner therapy can be safely offered as a contact tracing option and is also likely to be cost saving. Future research should find ways to increase uptake of accelerated partner therapy and develop alternative interventions for one-off sexual partners. FUNDING: National Institute for Health Research.

A rapid intrapartum test for group B Streptococcus to reduce antibiotic usage in mothers with risk factors: the GBS2 cluster RCT.

BACKGROUND: Mother-to-baby transmission of group B Streptococcus (Streptococcus agalactiae) is the main cause of early-onset infection. OBJECTIVES: We investigated if intrapartum antibiotic prophylaxis directed by a rapid intrapartum test reduces maternal and neonatal antibiotic use, compared with usual care (i.e. risk factor-directed antibiotics), among women with risk factors for vertical group B Streptococcus transmission, and examined the accuracy and cost-effectiveness of the rapid test. DESIGN: An unblinded cluster randomised controlled trial with a nested test accuracy study, an economic evaluation and a microbiology substudy. SETTING: UK maternity units were randomised to either a strategy of rapid test or usual care. PARTICIPANTS: Vaginal and rectal swabs were taken from women with risk factors for vertical group B Streptococcus transmission in established term labour. The accuracy of the GeneXpert® Dx IV GBS rapid testing system (Cepheid, Maurens-Scopont, France) was compared with the standard of selective enrichment culture in diagnosing maternal group B Streptococcus colonisation. MAIN OUTCOME MEASURES: Primary outcomes were rates of intrapartum antibiotic prophylaxis administered to prevent early-onset group B Streptococcus infection and accuracy estimates of the rapid test. Secondary outcomes were maternal antibiotics for any indication, neonatal antibiotic exposure, maternal antibiotic duration, neonatal group B Streptococcus colonisation, maternal and neonatal antibiotic resistance, neonatal morbidity and mortality, and cost-effectiveness of the strategies. RESULTS: Twenty-two maternity units were randomised and 20 were recruited. A total of 722 mothers (749 babies) participated in rapid test units and 906 mothers (951 babies) participated in usual-care units. There were no differences in the rates of intrapartum antibiotic prophylaxis for preventing early-onset group B Streptococcus infection in the rapid test units (41%, 297/716) compared with the usual-care units (36%, 328/906) (risk ratio 1.16, 95% confidence interval 0.83 to 1.64). There were no differences between the groups in intrapartum antibiotic administration for any indication (risk ratio 0.99, 95% confidence interval 0.81 to 1.21). Babies born in the rapid test units were 29% less likely to receive antibiotics (risk ratio 0.71, 95% confidence interval 0.54 to 0.95) than those born in usual-care units. The sensitivity and specificity of the rapid test were 86% (95% confidence interval 81% to 91%) and 89% (95% confidence interval 85% to 92%), respectively. In 14% of women (99/710), the rapid test was invalid or the machine failed to provide a result. In the economic analysis, the rapid test was shown to be both less effective and more costly and, therefore, dominated by usual care. Sensitivity analysis indicated potential lower costs for the rapid test strategy when neonatal costs were included. No serious adverse events were reported. CONCLUSIONS: The Group B Streptococcus 2 (GBS2) trial found no evidence that the rapid test reduces the rates of intrapartum antibiotic prophylaxis administered to prevent early-onset group B Streptococcus infection. The rapid test has the potential to reduce neonatal exposure to antibiotics, but economically is dominated by usual care. The accuracy of the test is within acceptable limits. FUTURE WORK: The role of routine testing for prevention of neonatal infection requires evaluation in a randomised controlled trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN74746075. FUNDING: 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. 12. See the NIHR Journals Library website for further project information.

WHAT IS THE PROBLEM?: Group B Streptococcus is a common bacterium found in the vagina and intestines of approximately one in four women. Group B Streptococcus may be passed to the baby around birth and cause severe infection. In the UK, women are offered antibiotics in labour to protect their baby from group B Streptococcus infection when specific risk factors are present. Most women with risk factors do not carry group B Streptococcus and their babies are unnecessarily exposed to antibiotics. Most women carrying group B Streptococcus do not have risk factors and so will not be offered antibiotics to protect their babies. WHAT DID WE PLAN TO DO?: We planned to find out if, for women with risk factors, a 'rapid test' in labour resulted in fewer women receiving antibiotics compared with 'usual care'. We also wanted to establish if the test correctly identified if mothers were carrying group B Streptococcus, helped reduce infections in babies and represented value for money. WHAT DID WE FIND?: We involved 1627 women (1700 babies) from 20 hospitals randomly allocated to rapid test or usual care. Using the 'rapid test' did not reduce antibiotics provided to mothers (41% in rapid test units and 36% in usual-care units). The test correctly identified 86% of women carrying group B Streptococcus, 89% of those who did not and failed to provide a result in 14% of women. A rapid test policy resulted in 13% fewer babies receiving antibiotics. The rapid test generated no cost savings when only the mothers' care was considered, but there was potential for reduced costs when including the newborns' hospital stay. WHAT DOES THIS MEAN?: The rapid test is accurate; however, using it for women with risk factors for their baby developing group B Streptococcus infection does not reduce antibiotic usage in mothers, although it does in babies. Value for money is uncertain and depends on what costs are included.

Rapid intrapartum test for maternal group B streptococcal colonisation and its effect on antibiotic use in labouring women with risk factors for early-onset neonatal infection (GBS2): cluster randomised trial with nested test accuracy study.

BACKGROUND: Mother-to-baby transmission of group B Streptococcus (GBS) is the main cause of early-onset infection. We evaluated whether, in women with clinical risk factors for early neonatal infection, the use of point-of-care rapid intrapartum test to detect maternal GBS colonisation reduces maternal antibiotic exposure compared with usual care, where antibiotics are administered due to those risk factors. We assessed the accuracy of the rapid test in diagnosing maternal GBS colonisation, against the reference standard of selective enrichment culture. METHODS: We undertook a parallel-group cluster randomised trial, with nested test accuracy study and microbiological sub-study. UK maternity units were randomised to a strategy of rapid test (GeneXpert GBS system, Cepheid) or usual care. Within units assigned to rapid testing, vaginal-rectal swabs were taken from women with risk factors for vertical GBS transmission in established term labour. The trial primary outcome was the proportion of women receiving intrapartum antibiotics to prevent neonatal early-onset GBS infection. The accuracy of the rapid test was compared against the standard of selective enrichment culture in diagnosing maternal GBS colonisation. Antibiotic resistance profiles were determined in paired maternal and infant samples. RESULTS: Twenty-two maternity units were randomised and 20 were recruited. A total of 722 mothers (749 babies) participated in rapid test units; 906 mothers (951 babies) were in usual care units. There was no evidence of a difference in the rates of intrapartum antibiotic prophylaxis (relative risk 1.16, 95% CI 0.83 to 1.64) between the rapid test (41%, 297/716) and usual care (36%, 328/906) units. No serious adverse events were reported. The sensitivity and specificity measures of the rapid test were 86% (95% CI 81 to 91%) and 89% (95% CI 85 to 92%), respectively. Babies born to mothers who carried antibiotic-resistant Escherichia coli were more likely to be colonised with antibiotic-resistant strains than those born to mothers with antibiotic-susceptible E. coli. CONCLUSION: The use of intrapartum rapid test to diagnose maternal GBS colonisation did not reduce the rates of antibiotics administered for preventing neonatal early-onset GBS infection than usual care, although with considerable uncertainty. The accuracy of the rapid test is within acceptable limits. TRIAL REGISTRATION: ISRCTN74746075 . Prospectively registered on 16 April 2015.

Mifepristone and misoprostol versus placebo and misoprostol for resolution of miscarriage in women diagnosed with missed miscarriage: the MifeMiso RCT.

TRIAL DESIGN: A randomised, parallel-group, double-blind, placebo-controlled multicentre study with health economic and nested qualitative studies to determine if mifepristone (Mifegyne®, Exelgyn, Paris, France) plus misoprostol is superior to misoprostol alone for the resolution of missed miscarriage. METHODS: Women diagnosed with missed miscarriage in the first 14 weeks of pregnancy were randomly assigned (1 : 1 ratio) to receive 200 mg of oral mifepristone or matched placebo, followed by 800 µg of misoprostol 2 days later. A web-based randomisation system allocated the women to the two groups, with minimisation for age, body mass index, parity, gestational age, amount of bleeding and randomising centre. The primary outcome was failure to pass the gestational sac within 7 days after randomisation. The prespecified key secondary outcome was requirement for surgery to resolve the miscarriage. A within-trial cost-effectiveness study and a nested qualitative study were also conducted. Women who completed the trial protocol were purposively approached to take part in an interview to explore their satisfaction with and the acceptability of medical management of missed miscarriage. RESULTS: A total of 711 women, from 28 hospitals in the UK, were randomised to receive either mifepristone plus misoprostol (357 women) or placebo plus misoprostol (354 women). The follow-up rate for the primary outcome was 98% (696 out of 711 women). The risk of failure to pass the gestational sac within 7 days was 17% (59 out of 348 women) in the mifepristone plus misoprostol group, compared with 24% (82 out of 348 women) in the placebo plus misoprostol group (risk ratio 0.73, 95% confidence interval 0.54 to 0.98; p = 0.04). Surgical intervention to resolve the miscarriage was needed in 17% (62 out of 355 women) in the mifepristone plus misoprostol group, compared with 25% (87 out of 353 women) in the placebo plus misoprostol group (risk ratio 0.70, 95% confidence interval 0.52 to 0.94; p = 0.02). There was no evidence of a difference in the incidence of adverse events between the two groups. A total of 42 women, 19 in the mifepristone plus misoprostol group and 23 in the placebo plus misoprostol group, took part in an interview. Women appeared to have a preference for active management of their miscarriage. Overall, when women experienced care that supported their psychological well-being throughout the care pathway, and information was delivered in a skilled and sensitive manner such that women felt informed and in control, they were more likely to express satisfaction with medical management. The use of mifepristone and misoprostol showed an absolute effect difference of 6.6% (95% confidence interval 0.7% to 12.5%). The average cost per woman was lower in the mifepristone plus misoprostol group, with a cost saving of £182 (95% confidence interval £26 to £338). Therefore, the use of mifepristone and misoprostol for the medical management of a missed miscarriage dominated the use of misoprostol alone. LIMITATIONS: The results from this trial are not generalisable to women diagnosed with incomplete miscarriage and the study does not allow for a comparison with expectant or surgical management of miscarriage. FUTURE WORK: Future work should use existing data to assess and rank the relative clinical effectiveness and safety profiles for all methods of management of miscarriage. CONCLUSIONS: Our trial showed that pre-treatment with mifepristone followed by misoprostol resulted in a higher rate of resolution of missed miscarriage than misoprostol treatment alone. Women were largely satisfied with medical management of missed miscarriage and would choose it again. The mifepristone and misoprostol intervention was shown to be cost-effective in comparison to misoprostol alone. TRIAL REGISTRATION: Current Controlled Trials ISRCTN17405024. FUNDING: 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. 25, No. 68. See the NIHR Journals Library website for further project information.

Miscarriage is a common complication of pregnancy, affecting approximately one in four women. Sometimes, medical treatment (i.e. tablets) may be offered to start or speed up the miscarriage process in order for the womb to empty itself. A drug called misoprostol (a tablet that makes the womb contract) is currently recommended for this treatment. However, the addition of another drug called mifepristone [a tablet that reduces pregnancy hormones (Mifegyne^®, Exelgyn, Paris, France)] might help the miscarriage to resolve more quickly. Therefore, we carried out the MifeMiso trial to test if mifepristone plus misoprostol is more effective than misoprostol alone in resolving miscarriage within 7 days. Women were randomly allocated by a computer to receive either mifepristone or placebo, followed by misoprostol 2 days later. Neither the women nor their health-care professionals knew which treatment they received. Some women also talked to the researchers about their experiences of taking part in the study. In total, 711 women were randomised to receive either mifepristone plus misoprostol or placebo plus misoprostol. Overall, 83% of women who received mifepristone plus misoprostol had miscarriage resolution within 7 days, compared with 76% of the women who received a placebo plus misoprostol. Surgery was required less often in women who received mifepristone plus misoprostol: 17% of women who received it required surgery, compared with 25% of women who received the placebo. Treatment with mifepristone did not appear to have any negative effects. Treatment with mifepristone plus misoprostol was more cost-effective than misoprostol alone, with an average saving of £182 per woman. Having taken part in the study, most women would choose medical management again and would recommend it to someone they knew who was experiencing a miscarriage.

Intersectoral costs of sexually transmitted infections (STIs) and HIV: a systematic review of cost-of-illness (COI) studies.

BACKGROUND: Sexually transmitted infections (STIs) and HIV can generate costs both within and outside the health sector (i.e. intersectoral costs). This systematic review aims (i) to explore the intersectoral costs associated with STIs and HIV considered in cost-of-illness (COI) studies, (ii) to categorise and analyse these costs according to cost sectors, and (iii) to illustrate the impact of intersectoral costs on the total cost burden. METHODS: Medline (PubMed), EMBASE (Ovid), Web of Science, CINAHL, PsycINFO, EconLit and NHS EED were searched between 2009 and 2019. Key search terms included terms for cost-of-illness, cost analysis and all terms for STIs including specific infections. Studies were included that assessed intersectoral costs. A standardised data extraction form was adopted. A cost component table was established based on pre-defined sector-specific classification schemes. Cost results for intersectoral costs were recorded. The quality of studies was assessed using a modified version of the CHEC-list. RESULTS: 75 COI studies were considered for title/abstract screening. Only six studies were available in full-text and eligible for data extraction and narrative synthesis. Intersectoral costs were captured in the following sectors: Patient & family, Informal care and Productivity (Paid Labour). Patient & family costs were addressed in four studies, including patient out-of-pocket payments/co-payments and travel costs. Informal care costs including unpaid (home) care support by family/friends and other caregiver costs were considered in three studies. All six studies estimated productivity costs for paid labour including costs in terms of absenteeism, disability, cease-to-work, presenteeism and premature death. Intersectoral costs largely contributed to the total economic cost burden of STIs and HIV. The quality assessment revealed methodological differences. CONCLUSIONS: It is evident that intersectoral costs associated with STIs and HIV are substantial. If relevant intersectoral costs are not included in cost analyses the total cost burden of STIs and HIV to society is severely underestimated. Therefore, intersectoral costs need to be addressed in order to ensure the total economic burden of STIs and HIV on society is assessed, and communicated to policy/decision-makers.

C-STICH2: emergency cervical cerclage to prevent miscarriage and preterm birth-study protocol for a randomised controlled trial.

BACKGROUND: Cervical cerclage is a recognised treatment to prevent late miscarriage and pre-term birth (PTB). Emergency cervical cerclage (ECC) for cervical dilatation with exposed unruptured membranes is less common and the potential benefits of cerclage are less certain. A randomised control trial is needed to accurately assess the effectiveness of ECC in preventing pregnancy loss compared to an expectant approach. METHODS: C-STICH2 is a multicentre randomised controlled trial in which women presenting with cervical dilatation and unruptured exposed membranes at 16 + 0 to 27 + 6 weeks gestation are randomised to ECC or expectant management. Trial design includes 18 month internal pilot with embedded qualitative process evaluation, minimal data set and a within-trial health economic analysis. Inclusion criteria are ≥16 years, singleton pregnancy, exposed membranes at the external os, gestation 16 + 0-27 + 6 weeks, and informed consent. Exclusion criteria are contraindication to cerclage, cerclage in situ or previous cerclage in this pregnancy. Randomisation occurs via an online service in a 1:1 ratio, using a minimisation algorithm to reduce chance imbalances in key prognostic variables (site, gestation and dilatation). Primary outcome is pregnancy loss; a composite including miscarriage, termination of pregnancy and perinatal mortality defined as stillbirth and neonatal death in the first week of life. Secondary outcomes include all core outcomes for PTB. Two-year development outcomes will be assessed using general health and Parent Report of Children's Abilities-Revised (PARCA-R) questionnaires. Intended sample size is 260 participants (130 each arm) based on 60% rate of pregnancy loss in the expectant management arm and 40% in the ECC arm, with 90% power and alpha 0.05. Analysis will be by intention-to-treat. DISCUSSION: To date there has been one small trial of ECC in 23 participants which included twin and singleton pregnancies. This small trial along with the largest observational study (n = 161) found ECC to prolong pregnancy duration and reduce deliveries before 34 weeks gestation. It is important to generate high quality evidence on the effectiveness of ECC in preventing pregnancy loss, and improve understanding of the prevalence of the condition and frequency of complications associated with ECC. An adequately powered RCT will provide the highest quality evidence regarding optimum care for these women and their babies. TRIAL REGISTRATION: ISRCTN Registry ISRCTN12981869 . Registered on 13th June 2018.

Preliminary model assessing the cost-effectiveness of preoperative chlorhexidine mouthwash at reducing postoperative pneumonia among abdominal surgery patients in South Africa.

BACKGROUND: Pneumonia is a common and severe complication of abdominal surgery, it is associated with increased length of hospital stay, healthcare costs, and mortality. Further, pulmonary complication rates have risen during the SARS-CoV-2 pandemic. This study explored the potential cost-effectiveness of administering preoperative chlorhexidine mouthwash versus no-mouthwash at reducing postoperative pneumonia among abdominal surgery patients. METHODS: A decision analytic model taking the South African healthcare provider perspective was constructed to compare costs and benefits of mouthwash versus no-mouthwash-surgery at 30 days after abdominal surgery. We assumed two scenarios: (i) the absence of COVID-19; (ii) the presence of COVID-19. Input parameters were collected from published literature including prospective cohort studies and expert opinion. Effectiveness was measured as proportion of pneumonia patients. Deterministic and probabilistic sensitivity analyses were performed to assess the impact of parameter uncertainties. The results of the probabilistic sensitivity analysis were presented using cost-effectiveness planes and cost-effectiveness acceptability curves. RESULTS: In the absence of COVID-19, mouthwash had lower average costs compared to no-mouthwash-surgery, $3,675 (R 63,770) versus $3,958 (R 68,683), and lower proportion of pneumonia patients, 0.029 versus 0.042 (dominance of mouthwash intervention). In the presence of COVID-19, the increase in pneumonia rate due to COVID-19, made mouthwash more dominant as it was more beneficial to reduce pneumonia patients through administering mouthwash. The cost-effectiveness acceptability curves shown that mouthwash surgery is likely to be cost-effective between $0 (R0) and $15,000 (R 260,220) willingness to pay thresholds. CONCLUSIONS: Both the absence and presence of SARS-CoV-2, mouthwash is likely to be cost saving intervention for reducing pneumonia after abdominal surgery. However, the available evidence for the effectiveness of mouthwash was extrapolated from cardiac surgery; there is now an urgent need for a robust clinical trial on the intervention on non-cardiac surgery.