Journal of Medical Economics

Aims: COVID-19 and influenza continue to impose a substantial burden on the Canadian healthcare system, particularly among adults aged greater than 65 years. This study compared the clinical and economic outcomes of a Stand-alone vaccination strategy with separate influenza and COVID-19 vaccines versus a Combination strategy incorporating mRNA-1083, an investigational vaccine targeting both infections. Methods: The study adopted the public healthcare payer perspective and adapted a previously published static model to predict COVID-19 and influenza infections across a one-year time horizon. Relative vaccine effectiveness (rVE) for mRNA-1083 against COVID-19 compared with the stand-alone vaccine (SPIKEVAX) was based on the pivotal clinical trial of mRNA-1083s COVID-19 component (mRNA-1283). For influenza, no incremental VE was assumed versus the adjuvanted stand-alone vaccine (FLUAD). Infections were modeled independently. Clinical outcomes included symptomatic infections, hospitalizations, and deaths. The economically justifiable price (EJP) was calculated at the willingness-to-pay (WTP) threshold of $50,000 per quality-adjusted life-year (QALY) gained. mRNA-1083 uptake was assumed to yield absolute increases in COVID-19 and influenza coverage by 10% and 3%, respectively. Results: Compared with the Stand-alone strategy, the Combination strategy was projected to reduce the number of COVID-19-related symptomatic infections, hospitalizations, and deaths (n=71,074; 5,008; 935, respectively), and corresponding influenza outcomes (n=3,985; 362; 69, respectively). The use of mRNA-1083 within the Combination strategy generated a cost-savings of $90,440,471 in vaccine administration fees and an EJP of $304 per dose. Results were sensitive to rVE, coverage, administration fees, mortality and incidence. Limitations: mRNA-1083s rVE is being evaluated in clinical trials and the impact of mRNA-1083 on vaccine coverage and administration fees is uncertain. Conclusions: mRNA-1083 may reduce the burden of COVID-19 and influenza in adults aged greater than 65 years in Canada, while offering good economic value because it has the potential to increase coverage and VE while reducing administration fees.

Breast cancer was the leading cause of cancer-related mortality among women worldwide in 2022. In Kenya, more than a quarter of breast cancer patients have the aggressive Human Epidermal Growth Factor Receptor 2 positive subtype. Trastuzumab is recommended for its treatment, but high costs have limited access. This study evaluated the cost-effectiveness and affordability of trastuzumab-based regimens to inform their adoption and use in Kenya. A cost-utility analysis was conducted from the healthcare payer perspective over a lifetime horizon. Five trastuzumab-based regimens of varying durations (9-week, 6-month, 9-month, 12-month, and 24-month) were compared with chemotherapy alone. Direct medical costs were estimated using a bottom-up micro-ingredient approach. All costs were reported in 2022 USD. A cohort Markov state-transition model with a monthly cycle length was used to estimate the costs and outcomes for an open hypothetical cohort. Scenario, deterministic sensitivity and probabilistic sensitivity analyses were conducted. A budget impact analysis estimated the financial implications of each regimen. The 9-week regimen had the lowest incremental cost-effectiveness ratio (ICER) of USD 3,230 per QALY, while the remaining regimens had ICERs ranging from USD 4,046 to 9,846 per QALY. The findings were most sensitive to the price and quantity utilized per cycle of trastuzumab. A reimbursement cap of KES 40,000 per cycle reduced ICERs by up to 61%. Over five years, the 9-week regimen would account for 1.2% of the projected insurers budget, whereas the current recommended 12-month regimen would consume 2.82%. Although none of the regimens were cost-effective at Kenyas WTP threshold (USD 1054.80), the 9-week regimen may still be considered by policymakers given its greater affordability. Further cost reductions can be achieved through negotiating lower drug prices, improving access to biosimilars, and implementing vial sharing.

Background Despite the significant impact of longstanding paediatric pneumococcal conjugate vaccine (PCV) use in the United Kingdom (UK), pneumococcal disease burden remains substantial and is primarily driven by nonPCV13 serotypes. Higher valent vaccines such as the 20 valent PCV (PCV20) may provide additional public health and economic benefits, yet their value in the contemporary UK setting has not been fully assessed using recent data. Methods We updated an age structured dynamic transmission model using post COVID 19 UK epidemiology (2001 to 2023) to compare pediatric PCV20 with PCV13 and PCV15. Over a 10 year horizon, we assessed cost effectiveness and number needed to vaccinate (NNV), capturing invasive and non invasive disease cases, deaths, costs, quality adjusted life years, and incremental cost effectiveness ratios. PCV20 was evaluated under 1+1 and 2+1 schedules; PCV13 and PCV15 were assessed under 1+1. Scenario analyses examined key uncertainties. Results PCV20 was estimated to avert more cases and deaths than PCV13 or PCV15, driven by broader serotype coverage and indirect effects. Both PCV20 schedules were dominant or cost saving versus lower valent comparators, with lower NNVs. PCV20s higher vaccination costs were offset by reductions in downstream healthcare expenditures. Conclusion Paediatric PCV20 implementation in the UK could deliver substantial health gains while improving economic efficiency, supporting timely adoption.

Suboptimal rotavirus vaccine effectiveness in low- and middle-income countries (LMICs) highlights the need for next-generation vaccines, such as the neonatal RV3-BB vaccine. However, there is uncertainty in the duration of protection and future price of vaccines in development. We aim to identify the conditions under which switching to RV3-BB is optimal in Malawi and Ghana, where the current immunization programs use 2-dose Rotarix and 3-dose Rotavac schedules, respectively. A full incremental cost-effectiveness analysis was performed using a validated transmission model calibrated to country-specific rotavirus data. Over 2025-2034, introducing RV3-BB resulted in the largest rotavirus-related burden reduction compared with the current country-specific programs. At moderate willingness-to-pay (~0.5 time Gross Domestic Product per capita), RV3-BB was preferred over Rotavac if price per dose was <$1.2 in Malawi and <$2.5 in Ghana, and/or if the average duration of protection exceeded 40 weeks in Malawi. The RV3-BB vaccine is likely to be cost-effective in Malawi and Ghana, as well as other LMICs, based on expected pricing and duration of protection.

Objectives: To evaluate if direct access to a Pregnancy Early Access Center (PEACE) improves the timeliness and efficiency of pregnancy loss care. Methods: We conducted a retrospective cohort study of patients diagnosed with EPL from January 2017 to December 2022 within a single healthcare system. We included EPL patients treated with procedural or medication management who had been assessed for a related early pregnancy complaint in the thirty days prior. The exposure was direct utilization of PEACE (yes/no) between first EPL symptom visit and EPL management. The primary outcome was "care latency" defined as days from initial presentation for concerning early pregnancy symptoms to initiation of active management. Secondary outcomes included "care continuity," the number of care teams encountered, "care efficiency," the number of patient encounters, and the type of EPL management received. Results: The evaluable cohort included 2151 individuals, with 36.5% patients of Black race and 30.3% publicly insured. A total of 885 (41.1%) received any EPL care at PEACE and 246 (11.4%) initiated their care at PEACE. Patients initiating care through PEACE experienced a 5-day reduction in care latency compared to patients who did not access PEACE. Adjusting for age, race, and insurance type, patients whose index EPL visit was with PEACE initiated their treatment twice as quickly as those who never saw PEACE (aHR 2.36 [95% CI, 2.05-2.71]). Care efficiency (median 2 [1-3] encounters) and care continuity (median 4.5 [4-7] care teams) were also improved by an index visit with PEACE when compared with controls (3 [2-4] and 6 [4-8] p<0.01), respectively). Conclusions: The Pregnancy Early Access Center (PEACE) model is associated with reduced care latency and improved efficiency and continuity when compared with routine care. PEACE reduces barriers to timely, patient-centered early pregnancy care.

Background: The impact of the Inflation Reduction Act (IRA) upon late-stage developments has been assumed to be limited. The Congressional Budget Office's IRA analysis excluded post-approval innovation, potentially overlooking substantial economic risks to drug developers and declines in the availability of treatments in areas of high unmet medical need such as oncology. Methods: A total of 1148 secondary trials from 364 FDA-approved medicines, published from 2018 to 2025, were obtained from Biomedtracker and clinicaltrials.gov. Using fractional multinomial logit, we model the share distribution of secondary indication studies across 19 disease groups and assess the change in this distribution post-IRA. We also assessed the number of secondary treatment studies pre- vs. post-IRA using multiple linear regression. Results: After the IRA's introduction, small molecule follow-on studies in oncology exhibited a statistically significant 35% decline (R2 = .48, p < 0.014) and lead indication small molecule oncology approvals exhibited a statistically significant 27% decline (R2 = .70, p < 0.002). We also find a statistically significant 14% decline in the share of orphan oncology studies pre- vs. post-IRA (p<0.001). Research Conclusions: This study's results refute claims that the IRA would have minimal negative effects on patient access or late-stage biopharmaceutical R&D. We hope this study reinvigorates debate about the law's unintended consequences and encourages thoughtful policy solutions, as the IRA manifestly creates disincentives that negatively impact patients seeking needed new medicines, particularly those requiring cures addressing metastatic late-stage cancers.

Introduction Care home (CH) influenza vaccination of staff improves resident health, yet uptake remains low at just over 11% (England, 2025/2026). We report an economic evaluation (EE) of "FluCare", an intervention to increase staff influenza vaccination through: vaccination clinics at CHs; promotional materials; and CH financial incentives. Method Seventy-five CHs were randomised to FluCare or control. A cost-consequence analysis took the influenza vaccination programme funder perspective, but also extended to the National Health Service (NHS) and CH perspective. Costs included: influenza vaccination; administration fee; FluCare components; CH resident NHS utilisation. Outcomes were: staff influenza vaccination rates; staff sickness; and resident mortality. Sensitivity analyses excluded intervention CHs that did not host vaccination clinics. Results Compared to control CHs, adjusted analysis found intervention homes with a mean absolute increase in vaccination rates of 1.8% (95% CI: -6.0%, 10.8%; p=0.572) at an increased cost of {pound}451 (95% CI: {pound}239, {pound}675; p<0.001) to the vaccination programme funders: {pound}249 per additional percentage point (PAPP) per CH. Vaccination clinics were delivered late in the influenza season, with 80% taking place from February 2023. Including only intervention CHs that hosted staff flu vaccination clinics (23/35), increases the mean difference to 10.1% (95% CI: 0.9%, 21.9%; p=0.018) and costs to {pound}805 (95% CI: {pound}603, {pound}1,079; p<0.001): {pound}79 PAPP per CH. Differences between trial arms in other costs and outcomes were marginal and generally non-significant. Conclusions FluCare delivered little improvement when staff flu vaccination clinics did not occur and had little impact on other costs/outcomes. Cost-effectiveness depends on willingness-to-pay for increased staff vaccination, but cost PAPP per CH improved from {pound}249 to {pound}79 when only CHs hosting clinics were considered. Late implementation, likely reduced impact by limiting clinic delivery, as reflected in sensitivity analysis. Future evaluations should implement FluCare earlier in the season.

Introduction: Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity and mortality, and low-dose aspirin (LDA) prophylaxis is the cornerstone of evidence-based prevention. Despite guideline recommendations, LDA adherence remains poor, with 10-25% of moderate-risk patients taking aspirin. Objective personalized risk stratification using biomarkers has been shown to motivate behavior change in other disease contexts. Survey data suggest that patients are more motivated to take aspirin if informed by an objective predictive test. Here, we report real-world LDA adherence among patients who received a high-risk result from a cell-free RNA (cfRNA) PE risk prediction test. Methods: This retrospective, observational survey study included asymptomatic patients of advanced maternal age (AMA; [&ge;] 35 years at delivery) with singleton pregnancies without USPSTF-defined preexisting high-risk conditions for PE who received the cfRNA PE risk prediction test. Patients who opted in to receive text message surveys were asked about LDA use following receipt of test results. High adherence was defined as reporting LDA use on at least 6 of 7 days per week at least 85% of the time surveyed. The primary analysis included patients with a high-risk test result and at least one LDA frequency survey response following receipt of test result. The observed proportion of adherent patients was compared to a baseline estimate of 25% using an exact binomial test. Results: Of 166 patients who received a cfRNA PE risk prediction test result, 48 (28.9%) received a high-risk result. Of these, 29 (60%) opted in and responded to at least one survey, constituting the primary analysis population. Twenty-seven of the 29 (93.1%; 95% CI: 78.0-98.1%) were classified as highly adherent, significantly higher than the 25% baseline adherence estimate for moderate-risk patients (p < 0.0001). Conclusion: Among surveyed patients who received a high-risk cfRNA PE test result, the proportion classified as highly adherent to LDA (93%) substantially exceeded published estimates of adherence in a similar patient population and met the clinically meaningful threshold of [&ge;] 80% associated with reduced risk of preterm preeclampsia. These findings indicate that objective and personalized biomarker risk testing may be a powerful driver of behavior change that current guidelines have failed to produce.

Abstract Introduction The ARRIVE trial first demonstrated that elective induction of labour (IOL) at 39 weeks in low-risk pregnancies reduced the likelihood of caesarean section (CS) without compromising perinatal safety; however, the generalizability of these findings remains debated, leading to uncertainty in clinical practice. The LIRIC trial aims to evaluate whether 39-week elective IOL reduces CS rates compared with expectant management, while exploring its impact on infant neurodevelopment and multi-omics profiles. Methods and analysis This is a single-centre, open-label, randomized controlled trial in China. A total of 1,074 low-risk pregnant women (nulliparous or multiparous) will be randomly assigned (1:1 ratio) to either 39-week IOL or expectant management. The primary outcome is the caesarean section (CS) rate. Secondary outcomes include a composite of severe neonatal morbidity and perinatal mortality and infant neurodevelopmental scores (Bayley-4 and ASQ-3), among others. Data analysis will follow the Intention-to-Treat (ITT) principle. Biospecimen will be collected for metagenomic and metabolomic analyses, with results to be reported separately. Ethics and dissemination The protocol has been approved by the Ethics Committee of Women's Hospital, School of Medicine, Zhejiang University. Informed consent will be obtained from all participants. Results will be disseminated via peer-reviewed journals, and standardized infant developmental reports will be provided to participants to enhance study benefit. Trial registration number NCT07082530.

Background: Colon capsule endoscopy (CCE) has been proposed as a non-invasive alternative to colonoscopy for colorectal cancer (CRC) screening, offering greater patient comfort and potentially reducing healthcare burden. However, its cost-effectiveness in population-based screening remains uncertain. Methods: This study used a state-transition (Markov) model to simulate lifetime outcomes of CRC screening in Denmark, Scotland, and Spain, comparing the standard pathway based on fecal immunochemical testing (FIT) followed by colonoscopy with an alternative pathway replacing colonoscopy with CCE after a positive FIT result. The model incorporated costs (2024 euros), quality-adjusted life-years (QALYs), and CRC cases avoided, applying a yearly discount rate of 3%. Deterministic sensitivity analyses explored uncertainty in capsule cost, adherence, and reinvestigation rates for non-advanced polyps. Results: Across all settings, CCE resulted in higher costs but slightly increased effectiveness and utility (mean QALYs 28.7 vs. 28.8; CRC detected 0.032-0.034 vs. 0.035-0.037 per person). Incremental cost-effectiveness ratios (ICER) ranged from 43,538EUR in Spain to 136,930EUR in Denmark per additional CRC detected. Capsule cost was the main driver of ICER variation, whereas adherence rates had minimal effect on cost-effectiveness. Changes in the prevalence of non-advanced polyps had a modest impact, except when capsule prices were high. Conclusions: Overall, replacing colonoscopy with CCE slightly increases detection and health gains at the expense of higher costs. Cost-effectiveness largely depends on capsule price and adherence. Artificial intelligence-assisted CCE interpretation may further improve diagnostic and economic performance, potentially supporting adoption in large-scale CRC screening programs.

Background: Statewide immunization data are essential for monitoring vaccination trends and evaluating immunization program impact. In the United States, Immunization Information Systems (IIS) were established in the early 1990s to collect these data; however, operational, legal, and procedural details vary across states and over time. This study summarized differences in IIS characteristics, such as legal requirements and reporting procedures, across U.S. states and jurisdictions over time. Methods: We analyzed survey data from previous work in 2000 and the Centers for Disease Control and Prevention (CDC) in 2012, 2018, and 2024. Our review focused on legislation and reporting requirements for immunization registries across 50 states and 14 jurisdictions, including U.S. territories and Freely Associated States. Results: Between 2000 and 2024, legal frameworks and reporting practices for immunization registries expanded across U.S. states and jurisdictions. The number of states with laws or administrative rules authorizing immunization registries increased from 24 states in 2000 to all 50 states, the District of Columbia, five metropolitan areas, five U.S. territories, and three Freely Associated States in 2024. Over the same period, reporting requirements also became more widespread. The number of states and jurisdictions mandating providers to report immunization records increased from 12 in 2000 to 54 in 2024. Consent policies also changed over time. By 2024, most states and jurisdictions had adopted implicit consent for reporting children's immunization records (41; 64%), while a smaller proportion required explicit parental consent (7; 11%) or implemented mandatory reporting without consent (14; 22%). Discussion: IIS infrastructure and reporting requirements have expanded across U.S. states and jurisdictions over the past two decades, while heterogeneity in consent policies and reporting practices persists. These temporal changes may need to be considered when interpreting IIS data, particularly in longitudinal and cross-jurisdictional analyses.

Background Lifestyle interventions can increase the probability of remission of prediabetes to normal glucose tolerance, but their economic value remains unclear. We assessed the within-trial and lifetime-horizon modeled cost-effectiveness of intensive and conventional lifestyle interventions in risk-stratified participants with prediabetes. Methods A health economic evaluation was conducted alongside the 12-month multicenter PLIS trial (n=1,105). High-risk participants were randomized to intensive (HR-INT) or conventional (HR-CONV); low-risk participants to conventional lifestyle intervention (LR-CONV) or control (only short single consultation; LR-CTRL) with risk stratification based on insulin secretion, insulin sensitivity, and liver fat content. Within-trial analyses estimated incremental costs per additional remission to normoglycemia and per quality-adjusted life year (QALY). Lifetime cost-effectiveness was modelled using a four-state Markov Model. Findings At 12 months, HR-INT and LR-CONV increased remission compared with their respective comparators. The incremental cost per additional remission was {euro}7,081 (95% CI: dominated-47,277) for HR-INT and {euro}4,278 (1,312-11,793) for LR-CONV from a health insurance perspective. A willingness-to-pay of {euro}22,000 (HR-INT) and {euro}7,500 (LR-CONV) per additional remission corresponded to 90% probability of cost-effectiveness. Neither intervention was cost-effective in terms of QALYs gained within the 12-months period. Lifetime modelling suggested that both HR-INT and LR-CONV are not only cost-effective, but also cost-saving, relative to HR-CONV and LR-CTRL, respectively. Also in the probabilistic sensitivity analysis, most simulations indicated dominance (71.7% for HR and 88% for LR). Interpretation Based on short-term economic evaluation, the interventions assessed were cost-effective regarding additional participants with remission, not for incremental QALYs gained. Lifetime modelling suggests cost savings for both risk groups. Targeting populations with lifestyle interventions to achieve prediabetes remission seems to generate good value for money in the long term.

Background. The recent approval of long-acting monoclonal antibodies (la-mAbs) and a maternal vaccine (MV) in the EU enables universal RSV prevention in infants. Modelling studies are widely used to quantify the population-level impact of alternative immunisation strategies. However, existing assessments of new RSV immunisation products focus on national or sub-national settings. Methods. We developed an age-stratified, stochastic compartmental model of RSV transmission for 28 EU/EEA countries. It combines literature-based parameters on RSV natural history and product efficacy with country-specific demographic and contact patterns. After model calibration against age- and country-specific RSV hospitalisation rates, we designed scenarios for both la-mAbs and MV at four coverage levels, with and without catch-up immunisation for infants under six months at season onset. We then evaluated each scenario against a no-immunisation baseline. Results. At 95% coverage, the cross-country median reduction in RSV hospitalisations over one season in infants under 12 months is 29.9% for la-mAbs (country median range: 27.7-33.9%) and 22.4% for MV (20.0-25.6%), scaling linearly with coverage. Out of all averted hospitalisations, 78.3% (90% CI: [67.3, 92.7]%) are concentrated in infants aged 0-2 months for la-mAbs and 72.7% (90\% CI: [61.4, 88.6]%) for MV. A catch-up campaign nearly doubles the overall reduction in RSV hospitalisations. Conclusions. Despite country-specific heterogeneities, impact of la-mAbs and MV is comparable across settings and herd-immunity effects are largely negligible. This supports harmonised European guidelines on coverage targets. Seasonal catch-up campaigns emerge as an effective lever to maximise the impact of immunisation programmes.

OBJECTIVES To quantify socioeconomic inequalities in antibiotic prescribing for common infections in primary care, and assess whether these inequalities arise from differences in consultation frequency, prescribing behaviour, or variation in vaccination uptake, smoking, and body mass index. DESIGN Population based cohort study. SETTING Primary care data from Clinical Practice Research Datalink, England. PARTICIPANTS 17,195,399 children and adults estimated to have been registered with a general practice in 2019. MAIN OUTCOME MEASURES Antibiotic prescribing rates (prescriptions per person-year), consultation rates (consultations per person-year), and probability of receiving an antibiotic prescription following consultation. RESULTS Higher deprivation was associated with higher antibiotic prescribing rates for most respiratory tract indications. In children, prescribing rates were 44.8% (95% confidence interval [CI] 41.9% to 47.7%) higher for upper respiratory tract infections and 47.6% (95% CI 44.2% to 51.3%) higher for lower respiratory tract infections in the most versus least deprived twentile. In adults, prescribing rates for lower respiratory tract infections were 22.7% (95% CI 21.4% to 24.1%) higher in the most deprived twentile. Prescribing rates for other indications showed weak, U-shaped, or negative associations with deprivation. Prescribing inequalities were primarily driven by inequalities in consultation rates rather than probability of receiving antibiotics once consulted. Lower influenza vaccination uptake partly accounted for higher consultation rates for respiratory infections among more deprived children, while smoking prevalence contributed to inequalities among adults. CONCLUSIONS Socioeconomic inequalities in antibiotic prescribing vary by indication type and are largely explained by consultation frequency. Reducing inequalities may require interventions that decrease the need to consult, e.g. improving influenza vaccination coverage in children and reducing smoking among adults, rather than focussing solely on prescribing behaviour.

We estimated the number needed to vaccinate (NNV) with an M72/AS01E-like vaccine to prevent one tuberculosis case in U.S. high-risk groups. Targeted vaccination of Mycobacterium tuberculosis-infected persons yielded NNVs of 217 (persons with HIV) to 2,486 (U.S.-born), within the range of established adult vaccines.

Importance: Several professional medical societies have removed race and ethnicity from widely used clinical algorithms with implications for millions of patients. Yet the opinions of patients and the public regarding the tensions underlying these pivotal changes have not been systematically explored. Objective: To assess global public opinion on the use of race or ethnicity in clinical algorithms, including preferences for different approaches to algorithmic reform and perceptions of alternative predictors. Design: Cross-sectional survey study. Setting: Multinational opt-in online survey conducted via Prolific in January 2026. Participants: A volunteer convenience sample with quota sampling to achieve approximately equal participation by sex at birth and across ten categories of self-identified race and ethnicity. Main Outcomes and Measures: Self-reported comfort with demographic and social predictors in clinical calculators, with net comfort defined as percentage extremely or somewhat comfortable minus percentage extremely or somewhat uncomfortable; preferences for race-specific versus race-free algorithms; perceptions of algorithmic harm or benefit. Results: Of 1,050 responses, 994 (94.7%) met eligibility criteria. Participants resided in 43 countries with a median age of 32.0 years (IQR, 26-41). Net comfort with the use of race or ethnicity in a hypothetical cancer risk calculator was +62.4% (95% CI: +57.8% to +66.9%), compared with +14.5% (95% CI: +9.1% to +19.9%) for postal or ZIP code. Overall, 87.9% (95% CI: 85.9% to 90.0%) were comfortable with race or ethnicity if a clinician explained its use and only 12.8% agreed race and ethnicity should never be used clinically. Across spirometry, kidney function, and cardiovascular risk calculators, 40.0% to 47.6% preferred race-specific versions, whereas 16.7% to 28.2% preferred race-free alternatives. Furthermore, a substantial proportion disagreed that they were well-represented by race and ethnicity categories, ranging from 22.1% for osteoporotic fracture risk equations to 42.9% for cardiovascular risk equations. These findings were consistent across countries, self-identified race and ethnicity, and among participants reporting prior experiences of racism in healthcare. Conclusions and Relevance: In our diverse multinational survey study, respondents were comfortable with the use of race and ethnicity across application areas, but often did not feel represented by existing categories and were less comfortable with the use of alternatives based on postal or ZIP codes.

ABSTRACT OBJECTIVE: We performed a systematic review and meta-analysis (SRMA) of post-surgical outcomes, comparing chlorhexidine gluconate (CHG) versus povidone iodine (PI) for vaginal antisepsis of major gynecologic procedures. DATA SOURCES: Ovid Medline, Embase, Scopus, Embase, Cochrane, and Clinicaltrials.gov were searched between 1986 and December 2023, for studies comparing CHG with PI for vaginal antisepsis of major gynecologic operations. STUDY ELIGIBILITY CRITERIA: We included Randomized Controlled Trials (RCTs) and non-RCTs comparing CHG to PI for vaginal antisepsis of major gynecologic operations. The primary outcome was surgical site infections (SSIs) and the secondary outcome was urinary tract infections (UTIs) and vaginal irritation. METHODS: Summary estimates were calculated by fixed effects models when I2 [&le;] 25% and by random effects models when I2 > 25%. Statistical analysis was performed using RevMan 5.4.1. The protocol for this systematic review was registered on PROSPERO (ID CRD42022378101). RESULTS: Nine studies met the inclusion criteria, four of which were randomized controlled trials (RCTs). 9538 patients were included, 4300 (45%) of whom were allocated to CHG and 5238 (55%) to PI. No statistically significant difference in SSI incidence was found for vaginal antisepsis with CHG versus PI in pooled analyses (n= 9538 patients; RR 1.20; 95% CI 0.92-1.57; I2 =0%). In contrast, a significantly higher risk of UTIs was observed for vaginal antisepsis with CHG than with PI (n=6061 patients; RR 1.48 95% CI 1.03-2.14; I2 = 0%). CONCLUSION: In our SRMA, there were no significant differences in SSI risk when either CHG or PI was utilized for antiseptic vaginal preparation. Interestingly, vaginal antisepsis with PI was associated with a lower incidence of post-operative UTIs following major gynecologic surgery. Our findings support current guidelines that form of vaginal antisepsis can be used for SSI prevention. They also suggest that PI may result in fewer postoperative UTIs but further randomized studies are needed to support these findings. Key words: surgical site infection, surgical wound infection, urinary tract infection, urogynecologic surgery, Chlorhexidine, Povidone Iodine, surgical antiseptic,

Background Early onset obesity in children, almost always accompanied by significant health complications, may be driven by rare genetic variants that influence appetite, metabolism, and nutrient absorption. Traditional treatment approaches are usually insufficient for those with monogenic obesity of this type. Glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide, and related drugs such as melanocortin 4 receptor agonists, have emerged as promising first-line treatments for severe obesity. There is no established protocol or pathway in England for identifying children with monogenic obesity who could benefit from these and similar treatments Methods We undertook early economic modelling to examine the cost-effectiveness, from a health service perspective, of implementing a new pharmacotherapeutic care pathway for the identification and treatment of monogenic obesity in children. We modelled a hypothetical population of children with hyperphagia and body mass index (BMI) three standard deviations above mean values for age and sex. We evaluated the clinical decision to initiate the pathway using a decision tree model with patient quality-adjusted life years (QALYs) and NHS healthcare costs 12 months from an initial clinic visit as outcomes, and calculated incremental cost effectiveness ratios and a cost-effectiveness acceptability curve. Results Both costs and QALYs were higher under further investigation (GBP3,247 and 0.47 QALYs) compared to no further investigation (GBP1,589 and 0.24 QALYs). The incremental cost-effectiveness ratio in the base case was GBP7,133 per QALY. Further examination of these children was therefore likely to be cost effective in this model. Conclusion A decision-tree model suggested that further investigation of severely obese children potentially eligible for treatment with semaglutide is likely to be cost-effective for the NHS. However, this result is associated with uncertainty arising from a lack of evidence for many key model parameters.

Background Planned caesarean birth (CB) is an increasingly utilised intervention, observed in almost 1 in 6 first-time mothers giving birth in the UK in 2023-24. Outcomes of planned (or actual) CB have been compared with planned (or actual) vaginal birth (VB) in a UK national guideline, but the scope of the comparison does not fully reflect the range of outcomes of interest to stakeholders. This review provides a comprehensive synthesis of outcomes of planned or actual CB with planned or actual VB to shape information resources which support informed birth planning. Methods The UK NICE Caesarean Birth Guideline NG192 evidence review of outcomes associated with planned CB (or actual CB where no planned CB data was available) was updated and expanded to incorporate additional outcomes prioritised by stakeholders. Results A total of 33 new study reports were combined with 32 reports previously included in NG192. All new reports were observational cohort studies or systematic reviews at low risk of bias. Only 3 studies reported outcomes of planned CB compared with planned VB (regardless of actual mode of birth), whereas all remaining studies reported actual VB outcomes. Planned CB was followed by more maternal infection (wound infection, mastitis, endometritis and urinary tract), venous thrombosis and lower neonatal unit admission rates than a planned VB. In the long-term, CB was linked to one or more sexual problems (insufficient lubrication and dyspareunia) being more common, future pregnancy being less common, and infertility being more frequent than after VB. For offspring, infant urinary tract infection after any CB, gastrointestinal tract infections and autism after planned CB were more common compared with VB. New findings highlight conflicting reports on childhood asthma and type 1 diabetes risk after planned CB, suggesting that prior positive associations may be explained by confounding. Existing evidence in NG192 suggests that cardiac arrest, maternal death and hysterectomy are more common after planned CB, but arise from studies at high risk of bias. NG192 also reports that placenta accreta and uterine rupture in a future pregnancy are more common after any CB. No new evidence was identified on these outcomes. Conclusion This review provides stakeholder-relevant information to populate decision-support materials on outcomes of planned (and actual) CB compared with planned (and actual) VB. The existing evidence base lacks data on long-term outcomes of planned (rather than actual) VB.

Background A mode of birth decision aid (DA) can provide information and support discussions about the potential risks and benefits (outcomes) associated with planning a vaginal or caesarean birth. Evidence shows that DAs can enhance patient knowledge, reduce decisional conflict, minimise inconsistencies in decision-making support, especially in maternity settings, and promote informed decision making. Despite these benefits, DAs specific to mode of birth are currently lacking in routine antenatal care. This paper outlines the process we followed to reach consensus on which outcomes of planned mode of birth should be included in a mode of birth DA. Methods Outcome identification and selection occurred in three phases. Phase 1 involved compiling a long list of outcomes from systematic reviews, the NICE Caesarean Birth Guidance and qualitative interviews with stakeholders. In Phase 2, this list was refined via a 2 round Delphi survey to prioritise outcomes considered important. An outcome reached consensus if [&ge;]70% of all participants, or 70% of women/partners rated it as critically important (7-9), and <15% rated it as not important (1-3). Phase 3 involved two stakeholder consensus meetings to finalise the outcome list. Results Seventy-one outcomes were identified. Following two Delphi rounds and consensus meetings, 54 outcomes were rated as critically important. Seventeen outcomes were consistently rated as not critical across both the survey and consensus phases, meaning that [&ge;]70% of participants in each phase did not consider them essential for informing women during pregnancy. Of these, 8 were retained due to NICE recommendations and ultimately, 9 outcomes were excluded. The final list included 44 maternal and 18 child outcomes. Maternal outcomes related to assistance with birth, complications at the time of birth, issues during recovery, pelvic floor, psychological issues, sexual function, and future pregnancy. Child outcomes related to morbidity and death, disease, obesity, issues with cognitive development and physical development. Conclusions Sixty-two priority outcomes were identified for inclusion in a planned mode of birth DA.