Pessaries (mechanical devices) for managing pelvic organ prolapse in women.

BACKGROUND: Pelvic organ prolapse is a common problem in women. About 40% of women will experience prolapse in their lifetime, with the proportion expected to rise in line with an ageing population. Women experience a variety of troublesome symptoms as a consequence of prolapse, including a feeling of 'something coming down' into the vagina, pain, urinary symptoms, bowel symptoms and sexual difficulties. Treatment for prolapse includes surgery, pelvic floor muscle training (PFMT) and vaginal pessaries. Vaginal pessaries are passive mechanical devices designed to support the vagina and hold the prolapsed organs back in the anatomically correct position. The most commonly used pessaries are made from polyvinyl-chloride, polythene, silicone or latex. Pessaries are frequently used by clinicians with high numbers of clinicians offering a pessary as first-line treatment for prolapse.  This is an update of a Cochrane Review first published in 2003 and last published in 2013. OBJECTIVES: To assess the effects of pessaries (mechanical devices) for managing pelvic organ prolapse in women; and summarise the principal findings of relevant economic evaluations of this intervention. SEARCH METHODS: We searched the Cochrane Incontinence Specialised Register which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 28 January 2020). We searched the reference lists of relevant articles and contacted the authors of included studies. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials which included a pessary for pelvic organ prolapse in at least one arm of the study. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed abstracts, extracted data, assessed risk of bias and carried out GRADE assessments with arbitration from a third review author if necessary. MAIN RESULTS: We included four studies involving a total of 478 women with various stages of prolapse, all of which took place in high-income countries. In one trial, only six of the 113 recruited women consented to random assignment to an intervention and no data are available for those six women. We could not perform any meta-analysis because each of the trials addressed a different comparison. None of the trials reported data about perceived resolution of prolapse symptoms or about psychological outcome measures. All studies reported data about perceived improvement of prolapse symptoms. Generally, the trials were at high risk of performance bias, due to lack of blinding, and low risk of selection bias. We downgraded the certainty of evidence for imprecision resulting from the low numbers of women participating in the trials. Pessary versus no treatment: at 12 months' follow-up, we are uncertain about the effect of pessaries compared with no treatment on perceived improvement of prolapse symptoms (mean difference (MD) in questionnaire scores -0.03, 95% confidence interval (CI) -0.61 to 0.55; 27 women; 1 study; very low-certainty evidence), and cure or improvement of sexual problems (MD -0.29, 95% CI -1.67 to 1.09; 27 women; 1 study; very low-certainty evidence). In this comparison we did not find any evidence relating to prolapse-specific quality of life or to the number of women experiencing adverse events (abnormal vaginal bleeding or de novo voiding difficulty). Pessary versus pelvic floor muscle training (PFMT): at 12 months' follow-up, we are uncertain if there is a difference between pessaries and PFMT in terms of women's perceived improvement in prolapse symptoms (MD -9.60, 95% CI -22.53 to 3.33; 137 women; low-certainty evidence), prolapse-specific quality of life (MD -3.30, 95% CI -8.70 to 15.30; 1 study; 116 women; low-certainty evidence), or cure or improvement of sexual problems (MD -2.30, 95% -5.20 to 0.60; 1 study; 48 women; low-certainty evidence). Pessaries may result in a large increase in risk of adverse events compared with PFMT (RR 75.25, 95% CI 4.70 to 1205.45; 1 study; 97 women; low-certainty evidence). Adverse events included increased vaginal discharge, and/or increased urinary incontinence and/or erosion or irritation of the vaginal walls. Pessary plus PFMT versus PFMT alone: at 12 months' follow-up, pessary plus PFMT probably leads to more women perceiving improvement in their prolapse symptoms compared with PFMT alone (RR 2.15, 95% CI 1.58 to 2.94; 1 study; 260 women; moderate-certainty evidence). At 12 months' follow-up, pessary plus PFMT probably improves women's prolapse-specific quality of life compared with PFMT alone (median (interquartile range (IQR)) POPIQ score: pessary plus PFMT 0.3 (0 to 22.2); 132 women; PFMT only 8.9 (0 to 64.9); 128 women; P = 0.02; moderate-certainty evidence). Pessary plus PFMT may slightly increase the risk of abnormal vaginal bleeding compared with PFMT alone (RR 2.18, 95% CI 0.69 to 6.91; 1 study; 260 women; low-certainty evidence). The evidence is uncertain if pessary plus PFMT has any effect on the risk of de novo voiding difficulty compared with PFMT alone (RR 1.32, 95% CI 0.54 to 3.19; 1 study; 189 women; low-certainty evidence). AUTHORS' CONCLUSIONS: We are uncertain if pessaries improve pelvic organ prolapse symptoms for women compared with no treatment or PFMT but pessaries in addition to PFMT probably improve women's pelvic organ prolapse symptoms and prolapse-specific quality of life. However, there may be an increased risk of adverse events with pessaries compared to PFMT. Future trials should recruit adequate numbers of women and measure clinically important outcomes such as prolapse specific quality of life and resolution of prolapse symptoms.   The review found two relevant economic evaluations. Of these, one assessed the cost-effectiveness of pessary treatment, expectant management and surgical procedures, and the other compared pessary treatment to PFMT.

Understanding the acceptability, barriers and facilitators for chlamydia and gonorrhoea screening in technical colleges: qualitative process evaluation of the "Test n Treat" trial.

BACKGROUND: Low uptake of sexually transmitted infection testing by sexually active young people is a worldwide public health problem. Screening in non-medical settings has been suggested as a method to improve uptake. The "Test n Treat" feasibility trial offered free, on-site rapid chlamydia/gonorrhoea tests with same day treatment for chlamydia (and gonorrhoea treatment at a local clinic,) to sexually active students (median age 17 years) at six technical colleges in London. Despite high rates of chlamydia (6% prevalence), uptake of testing was low (< 15%). In a qualitative study we explored the acceptability, including barriers and facilitators to uptake, of on-site chlamydia screening. METHODS: In 2016-17 we conducted a qualitative study in the interpretative tradition using face to face or telephone semi-structured interviews with students (n = 26), teaching staff (n = 3) and field researchers (n = 4). Interviews were digitally recorded, transcribed and thematically analysed. RESULTS: From the student perspective, feelings of embarrassment and the potential for stigma were deterrents to sexually transmitted infection testing. While the non-medical setting was viewed as mitigating against stigma, for some students volunteering to be screened exposed them to detrimental judgements by their peers. A small financial incentive to be screened was regarded as legitimising volunteering in a non-discrediting way. Staff and researchers confirmed these views. The very low level of knowledge about sexually transmitted infections influenced students to not view themselves as candidates for testing. There were also suggestions that some teenagers considered themselves invulnerable to sexually transmitted infections despite engaging in risky sexual behaviours. Students and researchers reported the strong influence peers had on uptake, or not, of sexually transmitted infection testing. CONCLUSIONS: This study offers new insights into the acceptability of college-based sexually transmitted infection screening to young, multi-ethnic students. Future studies in similar high risk, hard to reach groups should consider linking testing with education about sexually transmitted infections, offering non stigmatising incentives and engaging peer influencers.

Antimicrobial resistance point-of-care testing for gonorrhoea treatment regimens: cost-effectiveness and impact on ceftriaxone use of five hypothetical strategies compared with standard care in England sexual health clinics.

BackgroundWidespread ceftriaxone antimicrobial resistance (AMR) threatens Neisseria gonorrhoeae (NG) treatment, with few alternatives available. AMR point-of-care tests (AMR POCT) may enable alternative treatments, including abandoned regimens, sparing ceftriaxone use. We assessed cost-effectiveness of five hypothetical AMR POCT strategies: A-C included a second antibiotic alongside ceftriaxone; and D and E consisted of a single antibiotic alternative, compared with standard care (SC: ceftriaxone and azithromycin).AimAssess costs and effectiveness of AMR POCT strategies that optimise NG treatment and reduce ceftriaxone use.MethodsThe five AMR POCT treatment strategies were compared using a decision tree model simulating 38,870 NG-diagnosed England sexual health clinic (SHC) attendees; A micro-costing approach, representing cost to the SHC (for 2015/16), was employed. Primary outcomes were: total costs; percentage of patients given optimal treatment (regimens curing NG, without AMR); percentage of patients given non-ceftriaxone optimal treatment; cost-effectiveness (cost per optimal treatment gained).ResultsAll strategies cost more than SC. Strategy B (azithromycin and ciprofloxacin (azithromycin preferred); dual therapy) avoided most suboptimal treatments (n = 48) but cost most to implement (GBP 4,093,844 (EUR 5,474,656)). Strategy D (azithromycin AMR POCT; monotherapy) was most cost-effective for both cost per optimal treatments gained (GBP 414.67 (EUR 554.53)) and per ceftriaxone-sparing treatment (GBP 11.29 (EUR 15.09)) but with treatment failures (n = 34) and suboptimal treatments (n = 706).ConclusionsAMR POCT may enable improved antibiotic stewardship, but require net health system investment. A small reduction in test cost would enable monotherapy AMR POCT strategies to be cost-saving.

Performance of a Novel Point-of-Care Molecular Assay for Detection of Influenza A and B Viruses and Respiratory Syncytial Virus (Enigma MiniLab) in Children with Acute Respiratory Infection.

The performance of the Enigma MiniLab assay for influenza A and B viruses and respiratory syncytial virus (RSV) was compared to a centralized laboratory respiratory virus panel. The positive and negative percent agreement for influenza A virus, influenza B virus, and RSV were 79.2% (95% confidence interval [95% CI], 57.8 to 92.9%) and 99.4% (95% CI, 98.4 to 99.9), 100% (95% CI, 47.8 to 100%) and 100% (95% CI, 99.3 to 100%), 98.5% (95% CI, 94.6 to 99.8%) and 94.5% (95% CI, 91.9 to 96.4%), respectively.

Prospective evaluation of the cost of diagnosis and treatment of invasive fungal disease in a cohort of adult haematology patients in the UK.

OBJECTIVES: The direct cost of invasive fungal disease (IFD) includes antifungal drugs as well as diagnostic tests. The aim of this study was to determine these costs. METHODS: A total of 203 haematology patients were enrolled into the study and followed for a median of 556 days. Data were prospectively collected on antifungal drugs, diagnostic tests, length of stay and antibiotic usage. RESULTS: The overall mean (IQR) cost of care per patient (using UK-based reference costs) was £88 911 (45 339-121 594), £61 509 (39 748-78 383), £50 332 (23 037-72 057) and £34 075 (19 928-43 900) for proven/probable IFD, possible IFD, not classified and no evidence of IFD, respectively (P<0.001). The attributable cost of IFD was £54 836. Inpatient hospital stay accounted for nearly 74% of costs. In proven/probable IFD inpatient care, antifungals, antibiotics and IFD status accounted for 68%, 25%, 5% and 2%, respectively, compared with 85%, 11%, 2% and 2%, respectively, for no IFD (P<0.001). Among the allogeneic transplant patients, £36 914 (60%) of the total cost (£60 917) was used during the first 100 days. CONCLUSIONS: IFD was associated with longer length of stay and higher total overall cost of care, with attributable costs greater than £50 000 per case of IFD. Costs for inpatient stay far outstrip the cost of antifungal agents.

An early evaluation of clinical and economic costs and benefits of implementing point of care NAAT tests for Chlamydia trachomatis and Neisseria gonorrhoea in genitourinary medicine clinics in England.

OBJECTIVES: To estimate the costs and benefits of clinical pathways incorporating a point of care (POC) nucleic acid amplification test (NAAT) for chlamydia and gonorrhoea in genitourinary medicine (GUM) clinics compared with standard off-site laboratory testing. METHOD: We simulated 1.2 million GUM clinic attendees in England. A simulation in Microsoft Excel was developed to compare existing standard pathways of management for chlamydia and gonorrhoea with a POC NAAT. We conducted scenario analyses to evaluate the robustness of the model findings. The primary outcome was the incremental cost-effectiveness ratio. Secondary outcomes included the number of inappropriate treatments, complications and transmissions averted. RESULTS: The baseline cost of using the point of POC NAAT was £103.9 million compared with £115.6 million for standard care. The POC NAAT was also associated with a small increase of 46 quality adjusted life years, making the new test both more effective and cheaper. Over 95 000 inappropriate treatments might be avoided by using a POC NAAT. Patients receive diagnosis and treatment on the same day as testing, which may also prevent 189 cases of pelvic inflammatory disease and 17 561 onward transmissions annually. DISCUSSION: Replacing standard laboratory tests for chlamydia and gonorrhoea with a POC test could be cost saving and patients would benefit from more accurate diagnosis and less unnecessary treatment. Overtreatment currently accounts for about a tenth of the reported treatments for chlamydia and gonorrhoea and POC NAATs would effectively eliminate the need for presumptive treatment.

Mapping the Common Barriers to Optimal COPD Care in High and Middle-Income Countries: Qualitative Perspectives from Clinicians.

Purpose: Chronic obstructive pulmonary disease (COPD) poses a significant global health burden despite being largely preventable and treatable. Despite the availability of guidelines, COPD care remains suboptimal in many settings, including high-income countries (HICs) and upper-middle-income countries (UMICs), with varied approaches to diagnosis and management. This study aimed to identify common and unique barriers to COPD care across six countries (Australia, Spain, Taiwan, Argentina, Mexico, and Russia) to inform global policy initiatives for improved care. Methods: COPD care pathways were mapped for each country and supplemented with epidemiological, health-economic, and clinical data from a targeted literature review. Semi-structured interviews with 17 respiratory care clinicians were used to further validate the pathways and identify key barriers. Thematic content analysis was used to generate the themes. Results: Six themes were common in most HICs and UMICs: "Challenges in COPD diagnosis", "Strengthening the role of primary care", "Fragmented healthcare systems and coordination challenges", "Inadequate management of COPD exacerbations", "Limited access to specialized care" and, "Impact of underfinanced and overloaded healthcare systems". One theme, "Insurance coverage and reimbursement challenges", was more relevant for UMICs. HICs and UMICs differ in patient and healthcare provider awareness, primary care involvement, spirometry access, and availability of specialized care. Both face issues with healthcare fragmentation, guideline adherence, and COPD exacerbation management. In addition, UMICs also grapple with resource limitations and healthcare infrastructure challenges. Conclusion: Many challenges to COPD care are the same in both HICs and UMICs, underscoring the pervasive nature of these issues. While country-specific issues require customized solutions, there are untapped possibilities for implementing global respiratory strategies that support countries to manage COPD effectively. In addition to healthcare system-level initiatives, there is a crucial need for political prioritization of COPD to allocate the essential resources it requires.

An economic evaluation of two cervical screening algorithms in Belgium: HR-HPV primary compared to HR-HPV and liquid-based cytology co-testing.

OBJECTIVE: To assess the costs and benefits of two algorithms for cervical cancer screening in Belgium (1) high-risk human papillomavirus (HR-HPV) primary screening and (2) HR-HPV and liquid-based cytology (LBC) co-testing. METHODS: A decision tree was adapted from published work and parameterised using HORIZON study data and Belgian cost and population data. The theoretical model represents two different screening algorithms for a cohort of 577 846 women aged 25-64 attending routine cervical screening. Scenario analyses were used to explore the impact of including vaccinated women and alternative pricing approaches. Uncertainty analyses were conducted. RESULTS: The cost per woman screened was €113.50 for HR-HPV primary screening and €101.70 for co-testing, representing a total cost of €65 588 573 and €58 775 083, respectively, for the cohort; a 10% difference. For one screening cycle, compared to HR-HPV primary, co-testing resulted in 13 173 more colposcopies, 67 731 more HR-HPV tests and 477 020 more LBC tests. Co-testing identified 2351 more CIN2+ cases per year (27% more than HR-HPV primary) and 1602 more CIN3+ cases (24% more than HR-HPV primary) than HR-HPV primary. CONCLUSION: In Belgium, a co-testing algorithm could increase cervical pre-cancer detection rates compared to HR-HPV primary. Co-testing would cost less than HR-HPV primary if the cost of the HPV test and LBC were cost-neutral compared to the current cost of LBC screening but would cost more if the cost per HPV test and LBC were the same in both co-testing and HR-HPV primary strategies.

Pessaries (mechanical devices) for pelvic organ prolapse in women.

BACKGROUND: Pelvic organ prolapse is common, with some degree of prolapse seen in up to 50% of parous women in a clinic setting, although many are asymptomatic. The use of pessaries (a passive mechanical device designed to support the vagina) to treat prolapse is very common, and up to 77% of clinicians use pessaries for the first line management of prolapse. A number of symptoms may be associated with prolapse and treatments include surgery, pessaries and conservative therapies. A variety of pessaries are described which aim to alleviate the symptoms of prolapse and avert or delay the need for surgery. OBJECTIVES: To determine the effectiveness of pessaries (mechanical devices) for pelvic organ prolapse. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Register of trials (searched 13 March 2012), which includes searches of CENTRAL, MEDLINE, PREMEDLINE and handsearching of conference proceedings, and handsearched the abstracts of two relevant conferences held in 2011. We also searched the reference lists of relevant articles. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials which included a pessary for pelvic organ prolapse in one arm of the study. DATA COLLECTION AND ANALYSIS: Abstracts were assessed independently by two authors with arbitration from a third if necessary. Data extraction was completed independently for included studies by two review authors. MAIN RESULTS: To date there is only one published randomised controlled trial assessing the use of pessaries in the treatment of pelvic organ prolapse. AUTHORS' CONCLUSIONS: The review authors identified one randomised controlled trial comparing ring and Gellhorn pessaries. The results of the trial showed that both pessaries were effective for the approximately 60% of women who completed the study with no significant differences identified between the two types of pessary. However, methodological flaws were noted in the trial, as elaborated under risk of bias assessment. There is no consensus on the use of different types of device, the indications nor the pattern of replacement and follow-up care. There is an urgent need for randomised studies to address the use of pessaries in comparison with no treatment, surgery and conservative measures.

Determining the Relationship Between Seizure-Free Days and Other Predictors of Quality of Life in Patients with Dravet Syndrome and Their Carers from FFA Registration Studies.

INTRODUCTION: Dravet syndrome (DS) is a rare, lifelong epileptic encephalopathy characterised by frequent and severe seizures associated with premature mortality. Typically diagnosed in infancy, patients also experience progressive behavioural, motor-function and cognitive decline. Twenty percent of patients do not reach adulthood. Quality of life (QoL) is impaired for both patients and their carers. Reducing convulsive seizure frequency, increasing convulsive seizure-free days (SFDs) and improving patient/carer QoL are primary treatment goals in DS. This study explored the relationship between SFDs and patients' and carers' QoL to inform a cost-utility analysis of fenfluramine (FFA). METHODS: In FFA registration studies, patients (or their carer proxies) completed the Paediatric QoL inventory (PedsQL). These data were mapped to EuroQol-5 Dimensions Youth version (EQ-5D-Y) to provide patient utilities. Carer utilities were collected using EQ-5D-5L and mapped to EQ-5D-3L to align patient and carer QoL on the same scale. Linear mixed-effects and panel regression models were tested and Hausman tests identified the most appropriate approach for each group. On this basis, a linear mixed-effects regression model was used to examine the relationships between patient EQ-5D-Y and clinically relevant variables (age, frequency of SFDs per 28 days, motor impairments and treatment dose). A linear panel regression model examined the relationship between SFDs and carer QoL. RESULTS: After adjustment for age and underlying comorbidities, the patient regression model showed that SFDs per 28 days was a significant predictor of QoL. Each additional patient-SFD increased utility by 0.005 (p < 0.001). The carer linear panel model also showed that increasing SFDs per 28 days was a significant predictor of improved QoL. Each additional SFD increased carer utility by 0.014 (p < 0.001). CONCLUSION: This regression framework highlights that SFDs are significantly correlated with both patients' and carers' QoL. Treatment with effective antiseizure medications that increase SFDs directly improves QoL for patients and their carers.

Two self-sampling strategies for HPV primary cervical cancer screening compared with clinician-collected sampling: an economic evaluation.

OBJECTIVE: To compare the costs and effects of three sampling strategies for human papillomavirus (HPV) primary screening. DESIGN: Cost-consequence analysis from a health system perspective using a deterministic decision tree model. SETTING: England. PARTICIPANTS: A cohort of 10 000 women aged 25-65 years eligible for the National Health Service Cervical Screening Programme (NHSCSP). METHODS: The model was based on the NHSCSP HPV primary screening pathway and adapted for self-sampling. It used a 3-year cycle: routine screening (year 1) and recall screening (years 2/3). Parameter inputs were informed using published studies, NHSCSP reports and input from experts and manufacturers. Costs were from 2020/2021, British pound sterling (£). INTERVENTIONS: Three sampling strategies were implemented: (1) routine clinician-collected cervical sample, (2) self-collected first-void (FV) urine, (3) self-collected vaginal swab. The hypothetical self-sampling strategies involved mailing women a sampling kit. MAIN OUTCOME MEASURES: Primary outcomes: overall costs (for all screening steps to colposcopy), number of complete screens and cost per complete screen. SECONDARY OUTCOMES: number of women screened, number of women lost to follow-up, cost per colposcopy and total screening costs for a plausible range of uptake scenarios. RESULTS: In the base case, the average cost per complete screen was £56.81 for clinician-collected cervical sampling, £38.57 for FV urine self-sampling and £40.37 for vaginal self-sampling. In deterministic sensitivity analysis, the variables most affecting the average cost per screen were the cost of sample collection for clinician-collected sampling and the cost of laboratory HPV testing for the self-sampling strategies. Scaled to consider routine screening in England, if uptake in non-attenders increased by 15% and 50% of current screeners converted to self-sampling, the NHSCSP would save £19.2 million (FV urine) or £16.5 million (vaginal) per year. CONCLUSION: Self-sampling could provide a less costly alternative to clinician-collected sampling for routine HPV primary screening and offers opportunities to expand the reach of cervical screening to under-screened women.

Estimating the Health and Economic Impact of Improved Management in Prevalent Chronic Obstructive Pulmonary Disease Populations in England, Germany, Canada, and Japan: A Modelling Study.

Introduction: COPD is a leading cause of morbidity and mortality globally. Management is complex and costly. Although international quality standards for diagnosis and management exist, opportunities remain to improve outcomes, especially in reducing avoidable hospitalisations. Objective: To estimate the potential health and economic impact of improved adherence to guideline-recommended care for prevalent, on-treatment COPD populations in four high-income settings. Methods: A disease simulation model was developed to evaluate the impact of theoretical improvements to COPD management, comparing outcomes for usual care and policy scenarios for interventions that reduce avoidable hospitalisations: 1) increased attendance (50% vs 31-38%) of early follow-up review after severe exacerbation hospitalisation; 2) increased access (30% vs 5-10%) to an integrated disease management (IDM) programme that provides guideline adherent care. Results: For cohorts of 100,000 patients, Policy 1 yielded additional life years (England: 523; Germany: 759; Canada: 1316; Japan: 512) and lifetime cost savings (-£2.89 million; -€6.58 million; -$40.08 million; -¥735.58 million). For Policy 2, additional life years (2299; 3619; 3656) and higher lifetime total costs (£38.15 million; €35.58 million; ¥1091.53 million) were estimated in England, Germany and Japan, and additional life years (4299) and cost savings (-$20.52 million) in Canada. Scenarios found that the cost impact depended on the modelled intervention effect size. Conclusion: Interventions that reduce avoidable hospitalisations are estimated to improve survival and may generate cost savings. This study provides evidence on the theoretical impact of policies to improve COPD care and highlights priority areas for further research to support evidence-based policy decisions.

Health economic evaluation of an mRNA high-risk human papillomavirus (HR-HPV) assay versus a DNA HR-HPV assay for the proposed French cervical screening programme.

OBJECTIVE: Population screening programmes must make good use of resources for the health system and users. To evaluate impacts of the type of diagnostic test in the new French cervical screening programme, an messenger ribonucleic acid (mRNA) high-risk human papillomavirus assay was compared to a deoxyribonucleic acid (DNA) high-risk human papillomavirus assay for a hypothetical cohort of women aged 25 to 65 years. PERSPECTIVE: This evaluation takes the perspective of the French healthcare system. SETTING: France. METHODS: A decision tree model reflecting the French cervical screening algorithms was parametrised using French cost and population data and the Danish Horizon study. The outcomes were total costs, and number of colposcopies, HPV tests and cytology tests for the cohort. One-way and probabilistic sensitivity analyses and scenarios analyses were conducted to test the robustness of results to parameter and structural uncertainty. RESULTS: Adopting an mRNA versus DNA assay as part of national cervical screening in France is estimated to save €6.5 million (95% credibility intervals €-1.3 - €13.5 million) and prevent 47,795 (95% credibility intervals 35,309 - 60,139) unnecessary colposcopies, 38,666 unnecessary HPV tests and 121,670 cytology tests over two years for a cohort of 2,168,806 million women aged 25 to 65 years. Sensitivity analyses indicated robust results across a range of inputs. CONCLUSION: The choice of high-risk human papillomavirus assay makes a significant difference to resource use and costs and is important to consider when implementing cervical screening in France. Using an mRNA versus DNA assay can result in cost savings and reductions in unnecessary testing and procedures, which in turn benefits women and the health care system.

The cost-effectiveness of unilateral magnetic resonance-guided focused ultrasound in comparison with unilateral deep brain stimulation for the treatment of medically refractory essential tremor in England.

OBJECTIVES: This study aims to ascertain the cost-effectiveness of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of medically refractory Essential Tremor (mrET) in England. Essential Tremor (ET) is the most common movement disorder affecting approximately 1 million in the UK causing considerable societal impact affecting patients, carers and the wider healthservice. Medical treatment has mixed efficacy, with approximately 25-55% of ET medication refractory. Deep brain stimulation (DBS) is a proven neurosurgical treatment; however, the risks of surgery and anaesthesia mean some patients are ineligible. MRgFUS is an emerging noninvasive technique that causes tremor suppression by thermal ablation of tremor-sensitive brain tissue. Several international clinical trials have demonstrated MRgFUS is safe and clinically effective; however, to-date no cost-effectiveness study has been performed in Europe. METHODS: A Markov model was used to assess two subpopulations of mrET - those eligible and those ineligible for neurosurgery - in the context specific to England and its healthcare system. For those eligible for neurosurgery, MRgFUS was compared to DBS, the current standard treatment. For those ineligible for neurosurgery, MRgFUS was compared to treatment with medication alone. The model calculated the Incremental cost-effectiveness ratio (ICER) with appropriate sensitivity and scenario analyses. RESULTS: For those eligible for neurosurgery: In the model base case, the MRgFUS was economically dominant compared to DBS; MRgFUS was less costly (£19,779 vs £62,348) and more effective generating 0.03 additional quality-adjusted life-years (QALYs) per patient (3.71 vs 3.68) over the 5-year time horizon.For those ineligible for neurosurgery: In the model base case, MRgFUS cost over £16,000 per patient more than medication alone (£19,779 vs £62,348) but yielded 0.77 additional QALYs per patient(3.71 vs 2.95), producing an incremental cost-effectiveness ratio (ICER) of £20,851 per QALY. This ICER of £20,851 per QALY falls within the National Institute for Clinical Excellence's (NICE) willingness to pay threshold (WTP) of 20,000-30,000 demonstrating the cost-effectiveness profile of MRgFUS. CONCLUSION: This study demonstrates the favourable cost-effectiveness profile of MRgFUS for the treatment of mrET in England; in both patients suitable and not suitable for neurosurgery. ADVANCES IN KNOWLEDGE: The introduction of MRgFUS as a widely available ET treatment in UK is currently undergoing the necessary stages of regulatory approval. As the first European study, these favourable cost-effectiveness outcomes (notably the model base case ICER falling within NICE's WTP) can provide a basis for future commissioning of brain MRgFUS treatments in the UK, Europe and globally.

Qualitative Validation of COPD Evidenced Care Pathways in Japan, Canada, England, and Germany: Common Barriers to Optimal COPD Care.

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. A comprehensive and detailed understanding of COPD care pathways from pre-diagnosis to acute care is required to understand the common barriers to optimal COPD care across diverse health systems. Methods: Country-specific COPD care pathways were created for four high-income countries using international recommendations and country-specific guidelines, then populated with published epidemiological, clinical, and economic data. To refine and validate the pathways, semi-structured interviews using pre-prepared discussion guides and country-specific pathway maps were held with twenty-four primary and secondary care respiratory healthcare professionals. Thematic analysis was then performed on the interview transcripts. Results: The COPD care pathway showed broad consistency across the countries. Three key themes relating to barriers in optimal COPD management were identified across the countries: journey to diagnosis, treatment, and the impact of COVID-19. Common barriers included presentation to healthcare with advanced COPD, low COPD consideration, and sub-optimal acute and chronic disease management. COVID-19 has negatively impacted disease management across the pathway but presents opportunities to retain virtual consultations. Structural factors such as insurance and short duration of appointments also impacted the diagnosis and management of COPD. Conclusion: COPD is an important public health issue that needs urgent prioritization. The use of Evidenced Care Pathways with decision-makers can facilitate evidence-based decision making on interventions and policies to improve care and outcomes for patients and reduce unnecessary resource use and associated costs for the healthcare provider/payer.

What is the cost of pelvic inflammatory disease and how much could be prevented by screening for chlamydia trachomatis? Cost analysis of the Prevention of Pelvic Infection (POPI) trial.

OBJECTIVES: To describe healthcare settings attended by women with clinical pelvic inflammatory disease (PID), to calculate the cost of a PID episode and to estimate how many cases could be prevented in London annually at current chlamydia screening levels. METHODS: An ethnically diverse sample of 2259 16-24 year old, sexually active, female London students were recruited to a chlamydia screening trial in 2004-2006 of whom 94% (2115) were followed up after 12 months for incidence of PID. A cost analysis examined healthcare settings attended by women with PID, the cost of an episode of PID and the number of cases of PID in London due to untreated chlamydia at baseline that could be prevented per year at 2009 annual screening levels. RESULTS: Of 35 PID cases, 17 (47%) first presented in general practice, 15 (42%) at a genitourinary medicine clinic, two elsewhere and one was admitted to hospital. The average number of consultations for a PID episode was 2.0 (range 1-4) and the average cost was £163 (range £29-960). Assuming 414,345 sexually active women aged 16-24 in London, 6% chlamydia prevalence at baseline and a 7.3% difference in PID rates between screened and unscreened chlamydia positives, 391 (95% CI--44 to 882) cases of chlamydia-associated PID costing £63,733 could be prevented each year in London at 21.5% 2009 annual screening levels. CONCLUSIONS: Most women with PID were managed in the community. The number and cost of PID cases prevented by a single annual chlamydia screen is low suggesting that cost effectiveness may depend mainly on the prevention of long-term sequelae.

A health economic model to estimate the costs and benefits of an mRNA vs DNA high-risk HPV assay in a hypothetical HPV primary screening algorithm in Ontario, Canada.

This study models the impact of using two different types of high-risk (HR) human papillomavirus (HPV) tests: mRNA (Aptima) and DNA (Hybrid Capture 2) as part of a hypothetical primary HPV screening program in Ontario, Canada. Outcomes were the costs of the screening program, and number of colposcopies, HPV tests and cytology tests. Results were estimated for one cohort going through the screening algorithm. A decision tree model was adapted from a published UK study, with inputs drawn from published Canadian data for the probabilities through the model, costs, demographic, and screening data from Ontario. Sensitivity and scenario analyses explored uncertainty in the model inputs and assumptions. Results indicated that screening using an mRNA test could yield cost savings of CAD $4,007,266 (95% credibility interval [CI]: -7,866,251 - 8,035) compared to using a DNA test, with 10,639 (95% CI: 10,170 - 11,094) fewer women undergoing unnecessary colposcopies, and reductions in unnecessary HR-HPV and cytology tests. The HR-HPV test comprised the largest percentage of the costs saved, and the probability of being HPV positive in the first year had the biggest impact on results. These results indicate that the choice of HR-HPV test is important when implementing a primary HPV screening program to avoid unnecessary resource use and cost, which will benefit both women and healthcare providers.

Use of the Aptima mRNA high-risk human papillomavirus (HR-HPV) assay compared to a DNA HR-HPV assay in the English cervical screening programme: a decision tree model based economic evaluation.

OBJECTIVE: To estimate the impact of using the Aptima messenger RNA (mRNA) high-risk human papilloma virus (HR-HPV) assay versus a DNA HR-HPV assay in a primary HPV cervical screening programme. DESIGN: One hypothetical cohort followed for 3 years through HPV primary cervical screening. SETTING: England. PARTICIPANTS: A hypothetical cohort of women aged 25-65 years tested in the National Health Service (NHS) Cervical Screening Programme (CSP) for first call or routine recall testing. METHODS: A decision tree parameterised with data from the CSP (2017/18) and the HORIZON study. Uncertainty analyses were conducted using data from the FOCAL and GAST studies, other DNA HPV tests in addition to one-way and probabilistic sensitivity and scenarios analyses, to test the robustness of results. INTERVENTIONS: Aptima mRNA HR-HPV assay and a DNA HR-HPV assay (cobas 4800 HPV assay). MAIN OUTCOME MEASURES: Primary: total colposcopies and total costs for the cohort. Secondary: total HPV and cytology tests, number lost to follow-up. RESULTS: At baseline for a population of 2.25 million women, an estimated £15.4 million (95% credibility intervals (CI) £6.5 to 24.1 million) could be saved and 28 009 (95% CI 27 499 to 28 527) unnecessary colposcopies averted if Aptima mRNA assays are used instead of a DNA assay, with 90 605 fewer unnecessary HR-HPV and 253 477 cytology tests performed. These savings are due to a lower number of HPV positive samples in the mRNA arm. When data from other primary HPV screening trials were compared, results indicated that using the Aptima mRNA assay generated cost savings and reduced testing in every scenario. CONCLUSION: Using the Aptima mRNA assay versus a DNA assay would almost certainly yield cost savings and reduce unnecessary testing and procedures, benefiting the NHS and women in the CSP.

Estimating the costs of school closure for mitigating an influenza pandemic.

BACKGROUND: School closure is a key component of many countries' plans to mitigate the effect of an influenza pandemic. Although a number of studies have suggested that such a policy might reduce the incidence, there are no published studies of the cost of such policies. This study attempts to fill this knowledge gap METHODS: School closure is expected to lead to significant work absenteeism of working parents who are likely to be the main care givers to their dependent children at home. The cost of absenteeism due to school closure is calculated as the paid productivity loss of parental absenteeism during the period of school closure. The cost is estimated from societal perspective using a nationally representative survey. RESULTS: The results show that overall about 16% of the workforce is likely to be the main caregiver for dependent children and therefore likely to take absenteeism. This rises to 30% in the health and social care sector, as a large proportion of the workforce are women. The estimated costs of school closure are significant, at 0.2 pounds bn - 1.2 pounds bn per week. School closure is likely to significantly exacerbate the pressures on the health system through staff absenteeism. CONCLUSION: The estimates of school closure associated absenteeism and the projected cost would be useful for pandemic planning for business continuity, and for cost effectiveness evaluation of different pandemic influenza mitigation strategies.