Effects of Nurse Staffing on Missed Breastfeeding Support in Maternity Units With Different Nurse Work Environments.

PURPOSE: To examine the effect of nurse staffing in varying work environments on missed breastfeeding teaching and support in inpatient maternity units in the United States. BACKGROUND: Breast milk is the optimal food for newborns. Teaching and supporting women in breastfeeding are primarily a nurse's responsibility. Better maternity nurse staffing (fewer patients per nurse) is associated with less missed breastfeeding teaching and support and increased rates of breastfeeding. We examined the extent to which the nursing work environment, staffing, and nurse education were associated with missed breastfeeding care and how the work environment and staffing interacted to impact missed breastfeeding care. METHODS: In this cross-sectional study using the 2015 National Database of Nursing Quality Indicator survey, maternity nurses in hospitals in 48 states and the District of Columbia responded about their workplace and breastfeeding care. Clustered logistic regression models with interactions were used to estimate the effects of the nursing work environment and staffing on missed breastfeeding care. RESULTS: There were 19 486 registered nurses in 444 hospitals. Nearly 3 in 10 (28.2%) nurses reported missing breastfeeding care. In adjusted models, an additional patient per nurse was associated with a 39% increased odds of missed breastfeeding care. Furthermore, 1 standard deviation decrease in the work environment was associated with a 65% increased odds of missed breastfeeding care. In an interaction model, staffing only had a significant impact on missed breastfeeding care in poor work environments. CONCLUSIONS: We found that the work environment is more fundamental than staffing for ensuring that not only breastfeeding care is not missed but also breastfeeding care is sensitive to nurse staffing. Improvements to the work environment support the provision of breastfeeding care. IMPLICATIONS FOR RESEARCH AND PRACTICE: Both nurse staffing and the work environment are important for improving breastfeeding rates, but the work environment is foundational.

The Full Value of Vaccine Assessments Concept-Current Opportunities and Recommendations.

For vaccine development and adoption decisions, the 'Full Value of Vaccine Assessment' (FVVA) framework has been proposed by the WHO to expand the range of evidence available to support the prioritization of candidate vaccines for investment and eventual uptake by low- and middle-income countries. Recent applications of the FVVA framework have already shown benefits. Building on the success of these applications, we see important new opportunities to maximize the future utility of FVVAs to country and global stakeholders and provide a proof-of-concept for analyses in other areas of disease control and prevention. These opportunities include the following: (1) FVVA producers should aim to create evidence that explicitly meets the needs of multiple key FVVA consumers, (2) the WHO and other key stakeholders should develop standardized methodologies for FVVAs, as well as guidance for how different stakeholders can explicitly reflect their values within the FVVA framework, and (3) the WHO should convene experts to further develop and prioritize the research agenda for outcomes and benefits relevant to the FVVA and elucidate methodological approaches and opportunities for standardization not only for less well-established benefits, but also for any relevant research gaps. We encourage FVVA stakeholders to engage with these opportunities.

Estimating the Potential Public Health Value of BCG Revaccination.

An upcoming trial may provide further evidence that adolescent/adult-targeted BCG revaccination prevents sustained Mycobacterium tuberculosis infection, but its public health value depends on its impact on overall tuberculosis morbidity and mortality, which will remain unknown. Using previously calibrated models for India and South Africa, we simulated BCG revaccination assuming 45% prevention-of-infection efficacy, and we evaluated scenarios varying additional prevention-of-disease efficacy between +50% (reducing risk) and -50% (increasing risk). Given the assumed prevention-of-infection efficacy and range in prevention-of-disease efficacy, BCG revaccination may have a positive health impact and be cost-effective. This may be useful when considering future evaluations and implementation of adolescent/adult BCG revaccination.

Equity-Centered Postdischarge Support for Medicaid-Insured People: Protocol for a Type 1 Hybrid Effectiveness-Implementation Stepped Wedge Cluster Randomized Controlled Trial.

BACKGROUND: Disparities in posthospitalization outcomes for people with chronic medical conditions and insured by Medicaid are well documented, yet interventions that mitigate them are lacking. Prevailing transitional care interventions narrowly target people aged 65 years and older, with specific disease processes, or limitedly focus on individual-level behavioral change such as self-care or symptom management, thus failing to adequately provide a holistic approach to ensure an optimal posthospital care continuum. This study evaluates the implementation of THRIVE-an evidence-based, equity-focused clinical pathway that supports Medicaid-insured individuals with multiple chronic conditions transitioning from hospital to home by focusing on the social determinants of health and systemic and structural barriers in health care delivery. THRIVE services include coordinating care, standardizing interdisciplinary communication, and addressing unmet clinical and social needs following hospital discharge. OBJECTIVE: The study's objectives are to (1) examine referral patterns, 30-day readmission, and emergency department use for participants who receive THRIVE support services compared to those receiving usual care and (2) evaluate the implementation of the THRIVE clinical pathway, including fidelity, feasibility, appropriateness, and acceptability. METHODS: We will perform a sequential randomized rollout of THRIVE to case managers at the study hospital in 3 steps (4 in the first group, 4 in the second, and 5 in the third), and data collection will occur over 18 months. Inclusion criteria for THRIVE participation include (1) being Medicaid insured, dually enrolled in Medicaid and Medicare, or Medicaid eligible; (2) residing in Philadelphia; (3) having experienced a hospitalization at the study hospital for more than 24 hours with a planned discharge to home; (4) agreeing to home care at partner home care settings; and (5) being aged 18 years or older. Qualitative data will include interviews with clinicians involved in THRIVE, and quantitative data on health service use (ie, 30-day readmission, emergency department use, and primary and specialty care) will be derived from the electronic health record. RESULTS: This project was funded in January 2023 and approved by the institutional review board on March 10, 2023. Data collection will occur from March 2023 to July 2024. Results are expected to be published in 2025. CONCLUSIONS: The THRIVE clinical pathway aims to reduce disparities and improve postdischarge care transitions for Medicaid-insured patients through a system-level intervention that is acceptable for THRIVE participants, clinicians, and their teams in hospitals and home care settings. By using our equity-focused case management services and leveraging the power of the electronic medical record, THRIVE creates efficiencies by identifying high-need patients, improving communication across acute and community-based sectors, and driving evidence-based care coordination. This study will add important findings about how the infusion of equity-focused principles in the design and evaluation of evidence-based interventions contributes to both implementation and effectiveness outcomes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54211. TRIAL REGISTRATION: ClinicalTrials.gov NCT05714605; https://clinicaltrials.gov/ct2/show/NCT05714605.

Are Racial Disparities in Cesarean Due to Differences in Labor Induction Management?

OBJECTIVE: While there are known racial disparities in cesarean delivery (CD) rates, the exact etiologies for these disparities are multifaceted. We aimed to determine if differences in induction of labor (IOL) management contribute to these disparities. STUDY DESIGN: This retrospective cohort study evaluated all nulliparous patients with an unfavorable cervix and intact membranes who underwent IOL of a term, singleton gestation at a single institution from October 1, 2018, to September 30, 2020. IOL management was at clinician discretion. Patients were classified as Black, Indigenous, and People of Color (BIPOC) or White based on self-report. Overall rates of CD were compared for BIPOC versus White race. Chart review then evaluated various IOL management strategies as possible contributors to differences in CD by race. RESULTS: Of 1,261 eligible patients, 915 (72.6%) identified as BIPOC and 346 (27.4%) as White. BIPOC patients were more likely to be younger (26 years interquartile range (IQR) [22-30] vs. 32 years IQR [30-35], p < 0.001) and publicly insured (59.1 vs. 9.9%, p < 0.001). Indication for IOL and modified Bishop score also differed by race (p < 0.001; p = 0.006). There was 40% increased risk of CD for BIPOC patients, even when controlling for confounders (30.7 vs. 21.7%, p = 0.001; adjusted relative risk (aRR) 1.41, 95% confidence interval (CI) [1.06-1.86]). Despite this difference in CD, there were no identifiable differences in IOL management prior to decision for CD by race. Specifically, there were no differences in choice of cervical ripening agent, cervical dilation at or time to amniotomy, use and maximum dose of oxytocin, or dilation at CD. However, BIPOC patients were more likely to undergo CD for fetal indications and failed IOL. CONCLUSION: BIPOC nulliparas are 40% more likely to undergo CD during IOL than White patients within our institution. These data suggest that the disparity is not explained by differences in IOL management prior to cesarean, indicating that biases outside of induction management may be important to target to reduce CD disparities. KEY POINTS: · The etiologies for racial disparities in cesarean are likely multifaceted.. · In this work, there were no differences by race in measures of labor induction management.. · Biases outside of induction management during labor may be targeted to reduce CD disparities..

Modelling the health and economic impacts ofM72/AS01E vaccination and BCG-revaccination: Estimates for South Africa.

BACKGROUND: Tuberculosis remains a major public health problem in South Africa, with an estimated 300,000 cases and 55,000 deaths in 2021. New tuberculosis vaccines could play an important role in reducing this burden. Phase IIb trials have suggested efficacy of the M72/AS01E vaccine candidate and BCG-revaccination. The potential population impact of these vaccines is unknown. METHODS: We used an age-stratified transmission model of tuberculosis, calibrated to epidemiological data from South Africa, to estimate the potential health and economic impact of M72/AS01E vaccination and BCG-revaccination. We simulated M72/AS01E vaccination scenarios over the period 2030-2050 and BCG-revaccination scenarios over the period 2025-2050. We explored a range of product characteristics and delivery strategies. We calculated reductions in tuberculosis cases and deaths and costs and cost-effectiveness from health-system and societal perspectives. FINDINGS: M72/AS01E vaccination may have a larger impact than BCG-revaccination, averting approximately 80% more cases and deaths by 2050. Both vaccines were found to be cost-effective or cost saving (compared to no new vaccine) across a range of vaccine characteristics and delivery strategies from both the health system and societal perspective. The impact of M72/AS01E is dependent on the assumed efficacy of the vaccine in uninfected individuals. Extending BCG-revaccination to HIV-infected individuals on ART increased health impact by approximately 15%, but increased health system costs by approximately 70%. INTERPRETATION: Our results show that M72/AS01E vaccination or BCG-revaccination could be cost-effective in South Africa. However, there is considerable uncertainty in the estimated impact and costs due to uncertainty in vaccine characteristics and the choice of delivery strategy. FUNDING: This work was funded by the Bill & Melinda Gates Foundation (INV-001754). This work used the Cirrus UK National Tier-2 HPC Service at EPCC (https://www.cirrus.ac.uk) funded by the University of Edinburgh and EPSRC (EP/P020267/1).

The predictive role of symptoms in COVID-19 diagnostic models: A longitudinal insight.

To investigate the symptoms of SARS-CoV-2 infection, their dynamics and their discriminatory power for the disease using longitudinally, prospectively collected information reported at the time of their occurrence. We have analysed data from a large phase 3 clinical UK COVID-19 vaccine trial. The alpha variant was the predominant strain. Participants were assessed for SARS-CoV-2 infection via nasal/throat PCR at recruitment, vaccination appointments, and when symptomatic. Statistical techniques were implemented to infer estimates representative of the UK population, accounting for multiple symptomatic episodes associated with one individual. An optimal diagnostic model for SARS-CoV-2 infection was derived. The 4-month prevalence of SARS-CoV-2 was 2.1%; increasing to 19.4% (16.0%-22.7%) in participants reporting loss of appetite and 31.9% (27.1%-36.8%) in those with anosmia/ageusia. The model identified anosmia and/or ageusia, fever, congestion, and cough to be significantly associated with SARS-CoV-2 infection. Symptoms' dynamics were vastly different in the two groups; after a slow start peaking later and lasting longer in PCR+ participants, whilst exhibiting a consistent decline in PCR- participants, with, on average, fewer than 3 days of symptoms reported. Anosmia/ageusia peaked late in confirmed SARS-CoV-2 infection (day 12), indicating a low discrimination power for early disease diagnosis.

Developing a strategy to scale up place-based arts initiatives that support mental health and wellbeing: A realist evaluation of 'Arts for the Blues'.

Place-based arts initiatives are regarded as rooted in local need and as having capacity to engage local assets. However, many place-based arts initiatives remain poorly funded and short-lived, receiving little attention on how to scale up and sustain their activities. In this study we make a unique contribution to knowledge about scaling up place-based arts initiatives that support mental health and wellbeing through focusing on the example of 'Arts for the Blues', an arts-based psychological group intervention designed to reduce depression and improve wellbeing amongst primary care mental health service users in deprived communities. Methodologically, we used realist evaluation to refine the study's theoretical assumptions about scaling up, drawing on the lived and professional experiences of 225 diverse stakeholders' and frontline staff through a series of focus groups and evaluation questions at two stakeholders' events and four training days. Based on our findings, we recommend that to scale up place-based arts initiatives which support mental health and wellbeing: (i) the initiative needs to be adaptable, clear, collaborative, evidence-based, personalised and transformative; (ii) the organisation has to have a relevant need, have an understanding of the arts, has to have resources, inspiration and commitment from staff members, relevant skillsets and help from outside the organisation; (iii) at a policy level it is important to pay attention to attitude shifts towards the arts, meet rules, guidelines and standards expected from services, highlight gaps in provision, seek out early intervention and treatment options, and consider service delivery changes. The presence of champions at a local level and buy-in from managers, local leaders and policy makers are also needed alongside actively seeking to implement arts initiatives in different settings across geographical spread. Our theoretically-based and experientially-refined study provides the first ever scaling up framework developed for place-based arts initiatives that support the mental health and wellbeing, offering opportunities for spread and adoption of such projects in different organisational contexts, locally, nationally and internationally.

Improving the Timing of Acute Care Insulin Delivery.

LOCAL PROBLEM: Variations in nursing practice were observed across our hospital, a 520-bed acute care teaching facility in the northeast United States, regarding the timing and frequency of insulin administration in adult patients with diabetes. Chart audits noted that RNs administered insulin more than one hour after blood glucose results were obtained 97% of the time. In addition, insulin was given at bedtime only 37% of the time. PURPOSE: The purpose of this quality improvement (QI) project was to improve the care of inpatients requiring insulin by implementing protocols and adjusting practice to align with best practice recommendations. METHODS: The clinical nurse education specialist met with a team of staff nurses, providers, nurse leaders, and patient care technicians (PCTs) to formulate protocols and design interventions to ensure improvements in the quality of care for inpatients with diabetes. A sequence of education sessions and an online learning module were developed and assigned to nurses and PCTs to address knowledge gaps, specifically in the pharmacodynamics and safe administration of insulin, as well as how best to provide care to patients with diabetes. Monthly adherence data were disseminated to nurse leaders and educators and reviewed with clinical staff at daily safety huddles and staff meetings. Additional interventions to enhance nursing practice in caring for patients with diabetes included ensuring both bedtime insulin administration and timely insulin delivery. This project began in May 2017 and ended five years later. RESULTS: Two weeks after initial education sessions began in May and June 2017, the frequency of giving bedtime insulin based on the order set and according to the patient's blood glucose levels rose from 37% to 82%, and adherence to best practice protocols continued until final chart audits were performed in May 2022. The frequency of giving insulin less than one hour after obtaining blood glucose results improved from 3% to 64% between October and December 2019, and increased to a sustained level above the project's 92% goal two years later. CONCLUSION: Protocol development, targeted education, and audits with feedback led to improved care delivery for patients requiring insulin and increased nursing confidence.

Emergency Nurses' Well-Being in Magnet Hospitals and Recommendations for Improvements in Work Environments: A Multicenter Cross-Sectional Observational Study.

INTRODUCTION: This study aimed to determine the well-being outcomes and quality of work environment among emergency nurses compared with inpatient nurses working in Magnet hospitals and identify recommendations in emergency department work environments that hold promise for enhancing emergency nurses' well-being. METHODS: This is a cross-sectional analysis of multicenter survey data collected in 2021 from 11,743 nurses practicing in 60 United States Magnet hospitals. Nurses report on burnout, job dissatisfaction, intent to leave, work environment, and recommendations to improve well-being. RESULTS: Emergency nurses are significantly more likely to report high burnout (P = .04), job dissatisfaction (P < .001), and intent to leave (P < .001) than inpatient nurses working in the same Magnet hospitals. Emergency nurses are significantly more likely to report insufficient staffing (P = .001), an unfavorable work environment (P < .001), and lack confidence that management will act to resolve problems in patient care (P < .001) but did report significantly better working relationships with physicians (P < .001) than their inpatient counterparts. The 2 greatest recommendations to improve well-being included improving nurse staffing (91.4%) and the ability to take uninterrupted breaks (86.7%); the lowest-ranked recommendations were employing more advanced practice providers (25.9%) and appointing a wellness champion (21.2%). DISCUSSION: High burnout and other adverse nurse outcomes are common among emergency nurses in Magnet hospitals. Modifiable features of ED work environments including inadequate nurse staffing, inability of nurses to take uninterrupted breaks, and lack of responsiveness of management to persistent problems in patient care warrant high priority attention by Magnet hospital leaders.

Racial disparities in low-risk cesarean birth rates across hospitals.

BACKGROUND: We compared low-risk cesarean birth rates for Black and White women across hospitals serving increasing proportions of Black women and identified hospitals where Black women had low-risk cesarean rates less than or equal to White women. METHODS: In this cross-sectional analysis of secondary data from four states, we categorized hospitals by their proportion of Black women giving birth from "low" to "high". We analyzed the odds of low-risk cesarean for Black and White women across hospital categories. RESULTS: Our sample comprised 493 hospitals and the 65,524 Black and 251,426 White women at low risk for cesarean who birthed in them. The mean low-risk cesarean rate was significantly higher for Black, compared with White, women in the low (20.1% vs. 15.9%) and medium (18.1% vs. 16.9%) hospital categories. In regression models, no hospital structural characteristics were significantly associated with the odds of a Black woman having a low-risk cesarean. For White women, birthing in a hospital serving the highest proportion of Black women was associated with a 21% (95% CI: 1.01-1.44) increase in the odds of having a low-risk cesarean. DISCUSSION: Black women had higher odds of a low-risk cesarean than White women and were more likely to access care in hospitals with higher low-risk cesarean rates. The existence of hospitals where low-risk cesarean rates for Black women were less than or equal to those of White women was notable, given a predominant focus on hospitals where Black women have poorer outcomes. Efforts to decrease the low-risk cesarean rate should focus on (1) improving intrapartum care for Black women and (2) identifying differentiating organizational factors in hospitals where cesarean birth rates are optimally low and equivalent among racial groups as a basis for system-level policy efforts to improve equity and reduce cesarean birth rates.

PFAS Electroanalysis in Low-Oxygen River Water Using Electrogenerated Dioxygen.

Per- and polyfluoroalkyl substances (PFAS), nicknamed "forever chemicals" due to the strength of their carbon-fluorine bonds, are a class of potent micropollutants that cause deleterious health effects in mammals. The current state-of-the-art detection method requires the collection and transport of water samples to a centralized facility where chromatography and mass spectrometry are performed for the separation, identification, and quantification of PFAS. However, for efficient remediation efforts to be properly informed, a more rapid in-field testing method is required. We previously demonstrated the development and use of dioxygen as the mediator molecule. The use of dioxygen is predicated on the assumption that there will be consistent ambient dioxygen levels in natural waters. This is not always the case in hypoxic groundwater and at high altitudes. To overcome this challenge and further advance the strategies that will enable in-field electroanalysis of PFAS, we demonstrate, as a proof of concept, that dioxygen can be generated in solution through the hydrolysis of water. The electrogenerated dioxygen can then be used as a mediator molecule for the indirect detection of PFOS via molecularly imprinted polymer (MIP)-based electroanalysis. We demonstrate that calibration curves can be constructed with high precision and sensitivity (LOD < 1 ppt or 1 ng/L). Our results provide a foundation for enabling in-field hypoxic PFAS electroanalysis.

The potential health and economic impacts of new tuberculosis vaccines under varying delivery strategies in Delhi and Gujarat, India: a modelling study.

Background: India has the largest tuberculosis burden globally, but this burden varies nationwide. All-age tuberculosis prevalence in 2021 ranged from 747/100,000 in Delhi to 137/100,000 in Gujarat. Previous modelling has demonstrated the benefits and costs of introducing novel tuberculosis vaccines in India overall. However, no studies have compared the potential impact of tuberculosis vaccines in regions within India with differing tuberculosis disease and infection prevalence. We used mathematical modelling to investigate how the health and economic impact of two potential tuberculosis vaccines, M72/AS01E and BCG-revaccination, could differ in Delhi and Gujarat under varying delivery strategies. Methods: We applied a compartmental tuberculosis model separately for Delhi (higher disease and infection prevalence) and Gujarat (lower disease and infection prevalence), and projected epidemiological trends to 2050 assuming no new vaccine introduction. We simulated M72/AS01E and BCG-revaccination scenarios varying target ages and vaccine characteristics. We estimated cumulative cases, deaths, and disability-adjusted life years averted between 2025-2050 compared to the no-new-vaccine scenario and compared incremental cost-effectiveness ratios to three cost-effectiveness thresholds. Results: M72/AS01E averted a higher proportion of tuberculosis cases than BCG-revaccination in both regions (Delhi: 16.0% vs 8.3%, Gujarat: 8.5% vs 5.1%) and had higher vaccination costs (Delhi: USD$118 million vs USD$27 million, Gujarat: US$366 million vs US$97 million). M72/AS01E in Delhi could be cost-effective, or even cost-saving, for all modelled vaccine characteristics. M72/AS01E could be cost-effective in Gujarat, unless efficacy was assumed only for those with current infection at vaccination. BCG-revaccination could be cost-effective, or cost-saving, in both regions for all modelled vaccine scenarios. Discussion: M72/AS01E and BCG-revaccination could be impactful and cost-effective in Delhi and Gujarat. Differences in impact, costs, and cost-effectiveness between vaccines and regions, were determined partly by differences in disease and infection prevalence, and demography. Age-specific regional estimates of infection prevalence could help to inform delivery strategies for vaccines that may only be effective in people with a particular infection status. Evidence on the mechanism of effect of M72/AS01E and its effectiveness in uninfected individuals, which were important drivers of impact and cost-effectiveness, particularly in Gujarat, are also key to improve estimates of population-level impact.

Outcomes and experiences after child custody loss among mothers who use drugs: A mixed studies systematic review.

BACKGROUND: Mothers who use drugs are more likely to experience child custody loss than mothers who do not use drugs. The negative impact of removal on children has been well characterized in current literature while less is known about the impact of custody loss on mothers. The purpose of this mixed studies systematic review is to describe the state of science on the maternal outcomes and experiences after child custody loss among mothers who use drugs. METHODS: PubMed, PsycINFO, CINAHL, and Social Work Abstract databases were systematically searched between June 2022 to January 2023. Article eligibility criteria centered on the outcomes and experiences of mothers who use drugs after losing child custody. Studies were analyzed using results-based convergent synthesis methodology for mixed studies reviews. Study quality was assessed using the Mixed Methods Appraisal Tool (MMAT). A visual synthesis model was derived from combined results across all studies. RESULTS: Of 2434 articles screened, 22 relevant scientific articles were selected for inclusion. Longitudinal, cohort studies (n=4) and a cross-sectional study (n=1) identified positive associations between custody loss and poorer mental health, increased drug use and overdose risk, less treatment engagement, and worsened social factors. Qualitative studies (n=17) identified themes that described re-traumatization after child custody loss and the development of coping mechanisms through identity negotiation. CONCLUSION: Our findings indicate that child custody loss associated with drug use may exacerbate trauma and worsen maternal health. Immediate implications are provided for maternal health policy and practice in healthcare, child welfare, and legal professions.

New tuberculosis vaccines in India: modelling the potential health and economic impacts of adolescent/adult vaccination with M72/AS01E and BCG-revaccination.

BACKGROUND: India had an estimated 2.9 million tuberculosis cases and 506 thousand deaths in 2021. Novel vaccines effective in adolescents and adults could reduce this burden. M72/AS01E and BCG-revaccination have recently completed phase IIb trials and estimates of their population-level impact are needed. We estimated the potential health and economic impact of M72/AS01E and BCG-revaccination in India and investigated the impact of variation in vaccine characteristics and delivery strategies. METHODS: We developed an age-stratified compartmental tuberculosis transmission model for India calibrated to country-specific epidemiology. We projected baseline epidemiology to 2050 assuming no-new-vaccine introduction, and M72/AS01E and BCG-revaccination scenarios over 2025-2050 exploring uncertainty in product characteristics (vaccine efficacy, mechanism of effect, infection status required for vaccine efficacy, duration of protection) and implementation (achieved vaccine coverage and ages targeted). We estimated reductions in tuberculosis cases and deaths by each scenario compared to the no-new-vaccine baseline, as well as costs and cost-effectiveness from health-system and societal perspectives. RESULTS: M72/AS01E scenarios were predicted to avert 40% more tuberculosis cases and deaths by 2050 compared to BCG-revaccination scenarios. Cost-effectiveness ratios for M72/AS01E vaccines were around seven times higher than BCG-revaccination, but nearly all scenarios were cost-effective. The estimated average incremental cost was US$190 million for M72/AS01E and US$23 million for BCG-revaccination per year. Sources of uncertainty included whether M72/AS01E was efficacious in uninfected individuals at vaccination, and if BCG-revaccination could prevent disease. CONCLUSIONS: M72/AS01E and BCG-revaccination could be impactful and cost-effective in India. However, there is great uncertainty in impact, especially given the unknowns surrounding the mechanism of effect and infection status required for vaccine efficacy. Greater investment in vaccine development and delivery is needed to resolve these unknowns in vaccine product characteristics.

Is neglect of self-clearance biasing TB vaccine impact estimates?

BACKGROUND: Mathematical modelling has been used extensively to estimate the potential impact of new tuberculosis vaccines, with the majority of existing models assuming that individuals with Mycobacterium tuberculosis (Mtb) infection remain at lifelong risk of tuberculosis disease. Recent research provides evidence that self-clearance of Mtb infection may be common, which may affect the potential impact of new vaccines that only take in infected or uninfected individuals. We explored how the inclusion of self-clearance in models of tuberculosis affects the estimates of vaccine impact in China and India. METHODS: For both countries, we calibrated a tuberculosis model to a scenario without self-clearance and to various scenarios with self-clearance. To account for the current uncertainty in self-clearance properties, we varied the rate of self-clearance, and the level of protection against reinfection in self-cleared individuals. We introduced potential new vaccines in 2025, exploring vaccines that work in uninfected or infected individuals only, or that are effective regardless of infection status, and modelling scenarios with different levels of vaccine efficacy in self-cleared individuals. We then estimated the relative disease incidence reduction in 2050 for each vaccine compared with the no vaccination scenario. FINDINGS: The inclusion of self-clearance increased the estimated relative reductions in incidence in 2050 for vaccines effective only in uninfected individuals, by a maximum of 12% in China and 8% in India. The inclusion of self-clearance increased the estimated impact of vaccines only effective in infected individuals in some scenarios and decreased it in others, by a maximum of 14% in China and 15% in India. As would be expected, the inclusion of self-clearance had minimal impact on estimated reductions in incidence for vaccines that work regardless of infection status. INTERPRETATIONS: Our work suggests that the neglect of self-clearance in mathematical models of tuberculosis vaccines does not result in substantially biased estimates of tuberculosis vaccine impact. It may, however, mean that we are slightly underestimating the relative advantages of vaccines that work in uninfected individuals only compared with those that work in infected individuals.

The potential impact of novel tuberculosis vaccines on health equity and financial protection in low-income and middle-income countries.

INTRODUCTION: One in two patients developing tuberculosis (TB) in low-income and middle-income countries (LMICs) faces catastrophic household costs. We assessed the potential financial risk protection from introducing novel TB vaccines, and how health and economic benefits would be distributed across income quintiles. METHODS: We modelled the impact of introducing TB vaccines meeting the World Health Organization preferred product characteristics in 105 LMICs. For each country, we assessed the distribution of health gains, patient costs and household financial vulnerability following introduction of an infant vaccine and separately for an adolescent/adult vaccine, compared with a 'no-new-vaccine' counterfactual. Patient-incurred direct and indirect costs of TB disease exceeding 20% of annual household income were defined as catastrophic. RESULTS: Over 2028-2050, the health gains resulting from vaccine introduction were greatest in lower income quintiles, with the poorest 2 quintiles in each country accounting for 56% of total LMIC TB cases averted. Over this period, the infant vaccine was estimated to avert US$5.9 (95% uncertainty interval: US$5.3-6.5) billion in patient-incurred total costs, and the adolescent/adult vaccine was estimated to avert US$38.9 (US$36.6-41.5) billion. Additionally, 3.7 (3.3-4.1) million fewer households were projected to face catastrophic costs with the infant vaccine and 22.9 (21.4-24.5) million with the adolescent/adult vaccine, with 66% of gains accruing in the poorest 2 income quintiles. CONCLUSION: Under a range of assumptions, introducing novel TB vaccines would reduce income-based inequalities in the health and household economic outcomes of TB in LMICs.