The public economic burden of suboptimal type 2 diabetes control upon taxpayers in Sweden: Looking beyond health costs.

AIM: To estimate the fiscal burden for taxpayers in Sweden associated with type 2 diabetes (T2D) attributed to diabetes-related complications in patients failing to meet HbA1c targets. MATERIAL AND METHODS: We developed a public economic framework to assess how changes in diabetes-related complications influenced projected tax contributions and government disability payments for people with T2D. The analysis applied accepted disease-modelling practices to estimate different rates of diabetes-related complications based on an HbA1c of 6.9% (52 mmol/mol) and of 6.0% (42 mmol/mol). We adjusted the employment activity rates for those experiencing T2D-related events, applying age-specific earnings to estimate lifetime tax losses. Furthermore, the likelihood of receiving payments for health-related employment inactivity was estimated. Direct healthcare costs are excluded from this analysis. RESULTS: The estimated per person earnings loss for immediate and delayed HbA1c control was Swedish krona (SEK) 42 299 and SEK 44 157, respectively, over 10 years. The lost employment activity of people with T2D translates to lost tax revenues of SEK 23 265 and SEK 24 287 for immediate and delayed control, respectively. The estimated difference in disability payments was SEK 538. Combining the tax revenue loss and excess disability payments defines the broader fiscal costs, where we observe combined fiscal losses that favour immediate and sustained control by SEK 1560 over 10 years. CONCLUSIONS: We show that conducting fiscal analysis of diabetes interventions offers an enriched perspective capturing a range of costs that fall on government in relation to lost tax revenue and disability payments. Tax-financed health systems may benefit from broadening the consideration of costs and benefits when evaluating new interventions and treatment practices.

The 10-nm chromatin fiber and its relationship to interphase chromosome organization.

A chromosome is a single long DNA molecule assembled along its length with nucleosomes and proteins. During interphase, a mammalian chromosome exists as a highly organized supramolecular globule in the nucleus. Here, we discuss new insights into how genomic DNA is packaged and organized within interphase chromosomes. Our emphasis is on the structural principles that underlie chromosome organization, with a particular focus on the intrinsic contributions of the 10-nm chromatin fiber, but not the regular 30-nm fiber. We hypothesize that the hierarchical globular organization of an interphase chromosome is fundamentally established by the self-interacting properties of a 10-nm zig-zag array of nucleosomes, while histone post-translational modifications, histone variants, and chromatin-associated proteins serve to mold generic chromatin domains into specific structural and functional entities.

Economic Analysis of Vaccination Programs: An ISPOR Good Practices for Outcomes Research Task Force Report.

This report provides recommendations for budget holders and decision makers in high-, middle, and low-income countries requiring economic analyses of new vaccination programs to allocate scarce resources given budget constraints. ISPOR's Economic Evaluation of Vaccines Designed to Prevent Infectious Disease: Good Practices Task Force wrote guidelines for three analytic methods and solicited comments on them from external reviewers. Cost-effectiveness analyses use decision-analytic models to estimate cumulative changes in resource use, costs, and changes in quality- or disability-adjusted life-years attributable to changes in disease outcomes. Constrained optimization modeling uses a mathematical objective function to be optimized (e.g. disease cases avoided) for a target population for a set of interventions including vaccination programs within established constraints. Fiscal health modeling estimates changes in net present value of government revenues and expenditures attributable to changes in disease outcomes. The task force recommends that those designing economic analyses for new vaccination programs take into account the decision maker's policy objectives and country-specific decision context when estimating: uptake rate in the target population; vaccination program's impact on disease cases in the population over time using a dynamic transmission epidemiologic model; vaccination program implementation and operating costs; and the changes in costs and health outcomes of the target disease(s). The three approaches to economic analysis are complementary and can be used alone or together to estimate a vaccination program's economic value for national, regional, or subregional decision makers in high-, middle-, and low-income countries.

The Fiscal Consequences Attributed to Changes in Morbidity and Mortality Linked to Investments in Health Care: A Government Perspective Analytic Framework.

Governments have an enormous economic and political stake in the health of their populations. Population health is not only fundamental to economic growth but also affects short-term and long-term government expenditure on health care, disability, and other social programs and influences direct and indirect tax receipts. Fiscal transfers between citizen and state are mostly ignored in conventional welfare economics analyses based on the hypothesis that there are no winners or losers through transference of wealth. However, from the government perspective, this position is flawed, as disability costs and lost taxes attributed to poor health and reduced productive output represent real costs that pose budgetary and growth implications. To address the value of health and health care investments for government, we have developed a fiscal health analytic framework that captures how changes in morbidity and mortality influence tax revenue and transfer costs (e.g., disability, allowances, ongoing health costs). The framework can be used to evaluate the marginal impact of discrete investments or a mix of interventions in health care to inform governmental budgetary consequences. In this context, the framework can be considered as a fiscal budget impact and/or cost-benefit analysis model that accounts for how morbidity and mortality linked to specific programs represent both ongoing costs and tax revenue for government. Mathematical models identical to those used in cost-effectiveness analyses can be employed in fiscal analysis to reflect how disease progression influences public accounts (e.g., tax revenue and transfers).

Alterations in Aerobic Exercise Performance and Gait Economy Following High-Intensity Dynamic Stepping Training in Persons With Subacute Stroke.

BACKGROUND AND PURPOSE: Impairments in metabolic capacity and economy (O2cost) are hallmark characteristics of locomotor dysfunction following stroke. High-intensity (aerobic) training has been shown to improve peak oxygen consumption in this population, with fewer reports of changes in O2cost. However, particularly in persons with subacute stroke, inconsistent gains in walking function are observed with minimal associations with gains in metabolic parameters. The purpose of this study was to evaluate changes in aerobic exercise performance in participants with subacute stroke following high-intensity variable stepping training as compared with conventional therapy. METHODS: A secondary analysis was performed on data from a randomized controlled trial comparing high-intensity training with conventional interventions, and from the pilot study that formed the basis for the randomized controlled trial. Participants 1 to 6 months poststroke received 40 or fewer sessions of high-intensity variable stepping training (n = 21) or conventional interventions (n = 12). Assessments were performed at baseline (BSL), posttraining, and 2- to 3-month follow-up and included changes in submaximal (Equation is included in full-text article.)O2 ((Equation is included in full-text article.)O2submax) and O2cost at fastest possible treadmill speeds and peak speeds at BSL testing. RESULTS: Significant improvements were observed in (Equation is included in full-text article.)O2submax with less consistent improvements in O2cost, although individual responses varied substantially. Combined changes in both (Equation is included in full-text article.)O2submax and (Equation is included in full-text article.)O2 at matched peak BSL speeds revealed stronger correlations to improvements in walking function as compared with either measure alone. DISCUSSION AND CONCLUSIONS: High-intensity stepping training may elicit significant improvements in (Equation is included in full-text article.)O2submax, whereas changes in both peak capacity and economy better reflect gains in walking function. Providing high-intensity training to improve locomotor and aerobic exercise performance may increase the efficiency of rehabilitation sessions.Video Abstract available for more insights from the authors (see Supplemental Digital Content, http://links.lww.com/JNPT/A142).

Characterization of Cerebral Vascular Response to EEG Bursts Using ICP Pulse Waveform Template Matching.

Neurovascular coupling is the relationship between the activity of the brain and the subsequent change in blood flow to the active region. The most common methods of detecting neurovascular coupling are cumbersome and noncontinuous. However, the integration of intracranial pressure (ICP) and electroencephalography (EEG) may serve as an indirect measure of neurovascular coupling.This study used data collected from burst-suppressed patients who received both ICP and depth EEG monitoring. An adaptive thresholding algorithm was used to detect the start and end of each EEG burst. The morphological clustering and analysis of ICP and pulse morphological template-matching algorithms were then applied to derive several metrics describing the shape of the ICP pulse waveform and track how it changed following an EEG burst. These changes were compared using a template obtained from patients undergoing CO2-induced vasodilation.All segments exhibited a significant period of vasodilation within 1-2 s after burst, and 4 of 5 had a significant period of vasoconstriction within 4-11 s of the EEG burst, suggesting that there might be a characteristic response of vasodilation and subsequent vasoconstriction after a spontaneous EEG burst. Furthermore, these findings demonstrate the potential of integrated EEG and ICP as an indirect measure of neurovascular coupling.

Identification of an Intracranial Pressure (ICP) Response Function from Continuously Acquired Electroencephalographic and ICP Signals in Burst-Suppressed Patients.

Continuous intracranial pressure (ICP) and electroencephalographic (EEG) monitoring are used in the management of patients with brain injury. It is possible that these two signals could be related through neurovascular coupling. To explore this mechanism, we modeled the ICP response to brain activity by treating spontaneous burst activity in burst-suppressed patients as an impulse, and identified the ICP response function (ICPRF) as the subsequent change in ICP.Segments of ICP were filtered, classified as elevating or stable, and suitable ICPRFs were identified. After calibration, each ICPRF was convolved with the EEG to produce the estimated ICP. The mean error (ME) versus distance from the selected ICPRF was calculated and the elevating and stable ICP segments compared.Eighty-four ICPRFs were identified from 15 data segments. The ME of the elevating segments increased at an average rate of 57 mmHg/min, whereas the average ME of the stable segments increased at a rate of 0.05 mmHg/min.These findings demonstrate that deriving an ICPRF from a burst-suppressed patient is a suitable approach for stable segments. To completely model the ICP response to EEG activity, a more robust model should be developed.

Reproduction of ICP Waveform Changes in a Mathematical Model of the Cerebrospinal Circulatory System.

This study describes the establishment of a model of cerebral blood flow dynamics using cerebral blood flow velocity and intracranial pressure waveforms.

Remote Ischemic Conditioning Alters Methylation and Expression of Cell Cycle Genes in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: Remote ischemic conditioning (RIC) is a phenomenon in which short periods of nonfatal ischemia in 1 tissue confers protection to distant tissues. Here we performed a longitudinal human pilot study in patients with aneurysmal subarachnoid hemorrhage undergoing RIC by limb ischemia to compare changes in DNA methylation and transcriptome profiles before and after RIC. METHODS: Thirteen patients underwent 4 RIC sessions over 2 to 12 days after rupture of an intracranial aneurysm. We analyzed whole blood transcriptomes using RNA sequencing and genome-wide DNA methylomes using reduced representation bisulfite sequencing, both before and after RIC. We tested differential expression and differential methylation using an intraindividual paired study design and then overlapped the differential expression and differential methylation results for analyses of functional categories and protein-protein interactions. RESULTS: We observed 164 differential expression genes and 3493 differential methylation CpG sites after RIC, of which 204 CpG sites overlapped with 103 genes, enriched for pathways of cell cycle (P<3.8×10(-4)) and inflammatory responses (P<1.4×10(-4)). The cell cycle pathway genes form a significant protein-protein interaction network of tightly coexpressed genes (P<0.00001). CONCLUSIONS: Gene expression and DNA methylation changes in aneurysmal subarachnoid hemorrhage patients undergoing RIC are involved in coordinated cell cycle and inflammatory responses.

Health utility of patients with advanced gastrointestinal stromal tumors (GIST) after failure of imatinib and sunitinib: findings from GRID, a randomized, double-blind, placebo-controlled phase III study of regorafenib versus placebo.

BACKGROUND: In this analysis we report patients with advanced gastrointestinal stromal tumors (GIST) refractory to imatinib and sunitinib therapy as derived from the EuroQol-5D (EQ-5D) for progression-free (PF) and progressive disease health status. METHODS: Data were analyzed from a phase III trial conducted at 57 hospitals in 17 countries (trial registration number, NCT01271712). Patients with advanced GIST were randomized (2:1) to receive blinded treatment using oral regorafenib 160 mg daily or placebo, plus best supportive care (BSC) in both groups, for the first 3 weeks of each 4-week cycle. EQ-5D-3L was administered on day 1 of each cycle before contact with their physician and before any study-related procedures. The effect of disease progression on the utility of EQ-5D was tested with paired-samples comparison and general linear mixed modeling (GLMM). RESULTS: One hundred and eighty five patients [93 % of the intention-to-treat (ITT) population] completed 803 EQ-5D questionnaires: 77.7 % in progression-free (PF) state, 6.5 % at progression, 13.9 % following first progression, and 1.9 % after second progression. Mean baseline utility was 0.767 (SD 0.221) with no significant between-group differences for active treatment and BSC. The first post-progression health state was 0.647 (SD 0.343), suggesting significantly impaired health-related quality of life after confirmed disease progression showed a decrease of -0.120 (paired samples t test, p = 0.001). GLMM showed no effect of study treatment or cycle number on utility. CONCLUSIONS: We demonstrate a significant and clinically meaningful difference in health state utility values between PF and progression. Utility values remained stable over successive regorafenib cycles after controlling for disease status and treatment type.

Characterization of the relationship between intracranial pressure and electroencephalographic monitoring in burst-suppressed patients.

BACKGROUND: The objective of this study is to characterize the relationship between ICP and EEG METHODS: Simultaneous ICP and EEG data were obtained from burst-suppressed patients and segmented by EEG bursts. Segments were categorized as increasing/decreasing and peak/valley to investigate relationship between ICP changes and EEG burst duration. A generalized ICP response was obtained by averaging all segments time-aligned at burst onsets. A vasodilatation index (VDI) was derived from the ICP pulse waveform and calculated on a sliding interval to investigate cerebrovascular changes post-burst. RESULTS: Data from two patients contained 309 bursts. 246 ICP segments initially increased, of which 154 peaked. 63 ICP segments decreased, and zero reached a valley. The change in ICP (0.54 ± 0.85 mmHg) was significantly correlated with the burst duration (p < 0.001). Characterization of the ICP segments showed a peak at 8.1 s and a return to baseline at 14.7 s. The VDI for increasing segments was significantly elevated (median 0.56, IQR 0.31, p < 0.001) and correlated with burst duration (p < 0.001). CONCLUSIONS: Changes in the ICP and pulse waveform shape after EEG burst suggest that these signals can be related within the context of neurovascular coupling. SIGNIFICANCE: Existence of a physiological relationship between ICP and EEG may allow the study of neurovascular coupling in acute brain injury patients.

An economic assessment of embryo diagnostics (Dx) - the costs of introducing non-invasive embryo diagnostics into IVF standard treatment practices.

BACKGROUND: New techniques in assessing oocytes and embryo quality are currently explored to improve pregnancy and delivery rates per embryo transfer. While a better understanding of embryo quality could help optimize the existing "in vitro fertilization" (IVF) therapy schemes, it is essential to address the economic viability of such technologies in the healthcare setting. METHODS: An Embryo-Dx economic model was constructed to assess the cost-effectiveness of 3 different IVF strategies from a payer's perspective; it compares Embryo-Dx with single embryo transfer (SET) to elective single embryo transfer (eSET) and to double embryo transfer (DET) treatment practices. RESULTS: The introduction of a new non-invasive embryo technology (Embryo-Dx) associated with a cost up to €460 is cost-effective compared to eSET and DET based on the cost per live birth. The model assumed that Embryo-Dx will improve ongoing pregnancy rate/realize an absolute improvement in live births of 9% in this case. CONCLUSIONS: This study shows that improved embryo diagnosis combined with SET may have the potential to reduce the cost per live birth per couple treated in IVF treatment practices. The results of this study are likely more sensitive to changes in the ongoing pregnancy rate and consequently the live birth rate than the diagnosis costs. The introduction of a validated Embryo-Dx technology will further support a move towards increased eSET procedures in IVF clinical practice and vice versa.

Assessing the Fiscal Burden of Obesity in Canada by Applying a Public Economic Framework.

INTRODUCTION: Rising obesity prevalence is a health priority for many governments because of its impact on population health and economic consequences. We sought to estimate the broader consequences of obesity in Canada by applying a government perspective framework that captures lost tax revenues and increased government spending on social benefit programs. METHODS: An age-specific prevalence-based model was built to quantify the fiscal burden of disease for government attributed to people living with obesity. The model was populated with age-specific wages, employment activity and government benefits received to estimate taxes and transfer costs. A targeted literature search was conducted to identify modifiers of employment status, wages and disability status attributed to people with obesity, and applied to employment and epidemiological projections which enabled us to estimate government costs and tax losses. Government tax revenue and costs attributed to obesity were projected over a 10-year period and discounted at 3%. RESULTS: The fiscal burden of obesity in Canada is estimated at CAD$22,974 million (2021). This figure consists of obesity-attributed revenue losses of CAD$9404 million from direct taxes due to decreased employment activity and CAD$2374 million from indirect tax revenue losses due to reduced consumption taxes. Healthcare costs are estimated at CAD$7881 million annually and disability costs of CAD$3686 million annually. This fiscal burden of disease distributed amongst taxpayers in 2021 is estimated to be CAD$752 per capita. We estimate for every 1% reduction in obesity prevalence, CAD$229.7 million net fiscal gains can be achieved annually. CONCLUSIONS: Obesity is associated with substantial clinical and economic burden not only to the healthcare system but also to wider government budgets as demonstrated using fiscal analysis. Reductions in obesity prevalence are likely to have positive fiscal gains for government from reduced spending on public benefits and increased tax revenue attributed to employment changes.

"It just wasn't right down there": Surgical treatment of small bowel evisceration after hysterectomy with indocyanine green angiography, a case report.

This is a case of a 70-year-old female with small bowel evisceration through vaginal cuff dehiscence 14 months after hysterectomy. She presented with a loop of ileum herniated through the vagina. The bowel was irreducible and she was taken to the operating room for exploratory laparotomy, reduction of herniated bowel contents, and repair of vaginal cuff. During surgery, the eviscerated bowel had questionable viability and indocyanine green angiography was used to assess perfusion. After the repair of the vaginal cuff, indocyanine green angiography was performed and the bowel was saved from resection. In the discussion, light is shed upon the rarity of vaginal cuff dehiscence and the few cases of small bowel evisceration after a dehiscence. Possible causes of the evisceration, updates to technique, and recommendations for management are also discussed. The ultimate recommendation is for use of indocyanine green angiography in assessment of intestinal viability during surgical exploration for small bowel evisceration.

Fiscal analysis of the pediatric immunization program in Belgium applying a lifetime government perspective framework.

OBJECTIVES: A public economic framework was used to explore lifetime government costs and benefits in relation to the Pediatric Immunization Program (PIP) in Belgium based on cases and deaths averted. METHODS: To estimate changes in net government revenue, we developed a decision-analytic model that quantifies lifetime tax revenues and transfers based on changes in morbidity and mortality arising from Belgium's Pediatric Immunization Program (PIP). The model considered differences in incidence rates with vaccines included in Belgium's PIP: compared with the pre-vaccine era. Changes in deaths and comorbid conditions attributed to PIP on the Belgium 2020 birth cohort were used to estimate gross lifetime earnings changes, tax revenue gains attributed to averted morbidity and mortality avoidance, disability transfer cost savings, and averted special education costs associated with each vaccine. RESULTS: Vaccinating a single birth cohort according to the PIP gives rise to fiscal gains of €56 million in averted tax revenue loss, €8 million disability savings, and €6 million special education cost-savings. Based on the costs of implementing the PIP, we estimate the fiscal benefit-cost ratio (fBCR) of €2.2 investment return for the government from every €1 invested excluding longevity costs. CONCLUSIONS: Reducing vaccine-preventable conditions generates tax revenue for the government, providing fiscal justification for sustained immunization investments.

Irregular optogenetic stimulation waveforms can induce naturalistic patterns of hippocampal spectral activity.

Objective. Therapeutic brain stimulation is conventionally delivered using constant-frequency stimulation pulses. Several recent clinical studies have explored how unconventional and irregular temporal stimulation patterns could enable better therapy. However, it is challenging to understand which irregular patterns are most effective for different therapeutic applications given the massively high-dimensional parameter space.Approach. Here we applied many irregular stimulation patterns in a single neural circuit to demonstrate how they can enable new dimensions of neural control compared to conventional stimulation, to guide future exploration of novel stimulation patterns in translational settings. We optogenetically excited the septohippocampal circuit with constant-frequency, nested pulse, sinusoidal, and randomized stimulation waveforms, systematically varying their amplitude and frequency parameters.Main results.We first found equal entrainment of hippocampal oscillations: all waveforms provided similar gamma-power increase, whereas no parameters increased theta-band power above baseline (despite the mechanistic role of the medial septum in driving hippocampal theta oscillations). We then compared each of the effects of each waveform on high-dimensional multi-band activity states using dimensionality reduction methods. Strikingly, we found that conventional stimulation drove predominantly 'artificial' (different from behavioral activity) effects, whereas all irregular waveforms induced activity patterns that more closely resembled behavioral activity.Significance. Our findings suggest that irregular stimulation patterns are not useful when the desired mechanism is to suppress or enhance a single frequency band. However, novel stimulation patterns may provide the greatest benefit for neural control applications where entraining a particular mixture of bands (e.g. if they are associated with different symptoms) or behaviorally-relevant activity is desired.

Estimating Public Economic Gains from Early Breast Cancer and Curative Treatment: A Case Study in Human Epidermal Growth Factor Receptor (HER-2) Positive Targeted Therapies.

INTRODUCTION: Cancer diagnosis influences the choices that patients make regarding current and future labor market activity. These choices have implications for governments based on resulting changes in taxes paid and benefits received. In this analysis we explore how human growth receptor 2 (HER2)-positive residual invasive breast cancer and different treatments influence government accounts excluding health costs. METHODS: HER2-positive early breast cancer (eBC) health states from a published disease model were used to establish likelihood of working and wage impact at different stages of disease. The indirect productivity losses for an average woman aged 49 years were translated into fiscal consequences to government by applying an established government perspective-modeling framework. The fiscal projections (discounted) include gross tax revenue by disease stage, government transfer costs related to time off work and early retirement ,and net fiscal balance (e.g., gross taxes-transfers) in three countries Canada, Portugal, and Brazil. RESULTS: The net fiscal balance in Canada for a healthy woman was C$109,551 compared with a HER2-positive eBC woman treated with trastuzumab emtansine (C$69,767) or trastuzumab (C$62,971). A similar pattern was observed in the three countries but reflecting the overall tax burden in each country, labor force activity, and available public benefits. Age at diagnosis was an important determinant of the likely net fiscal balance, as this influences the remaining working years. DISCUSSION: Women diagnosed with HER2-positive eBC were estimated to pay less lifetime gross taxes and receive more in sickness benefits compared with healthy women. Treatments that improve outcomes are likely to offer fiscal gains for government from improved work force participation.

Identifying characteristics that enable resilient immunisation programmes: a scoping review.

OBJECTIVES: The COVID-19 pandemic highlighted the fragility of immunisation programmes and resulted in a significant reduction in vaccination rates, with increasing vaccine-preventable disease outbreaks consequently reported. These vulnerabilities underscore the importance of resilient immunisation programmes to ensure optimal performance during crises. To date, a framework for assessing immunisation programme resilience does not exist. We conducted a scoping review of immunisation programmes during times of crisis to identify factors that characterise resilient immunisation programmes, which may inform an Immunisation Programme Resilience Tool. DESIGN: Scoping review design followed the Arksey and O'Malley framework, and manuscript reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines. DATA SOURCES: CINAHL, CENTRAL, Embase, Google Scholar, MEDLINE, PsycINFO and Web of Science and databases were searched between 1 January 2011 and 2 September 2023. Citation searching of identified studies was also performed. ELIGIBILITY CRITERIA: We included primary empirical peer-reviewed studies that discussed the resilience of immunisation programme to crises, shocks or disruptions. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened records and performed data extraction. We extracted data on study location and design, crisis description, and resilience characteristics discussed, and identified evidence gaps in the literature. Findings were synthesised using tabulation and an evidence gap map. RESULTS: Thirty-seven studies met the eligibility criteria. These studies captured research conducted across six continents, with most concentrated in Africa, Asia and Europe. One study had a randomised controlled trial design, while 36 studies had observational designs (15 analytical and 21 descriptive). We identified five characteristics of resilient immunisation programmes drawing on the Health System Resilience Index (Integration, Awareness, Resource Availability and Access, Adaptiveness and Self-regulation) and several evidence gaps in the literature. CONCLUSIONS: To our knowledge, no immunisation programme resilience tool exists. We identified factors from the Health System Resilience Index coupled with factors identified through primary empirical evidence, which may inform development of an immunisation programme resilience tool.

Identifying factors that can be used to assess a country's readiness to deploy a new vaccine or improve uptake of an underutilised vaccine: a scoping review.

OBJECTIVES: Identifying whether a country is ready to deploy a new vaccine or improve uptake of an existing vaccine requires knowledge of a diverse range of interdependent, context-specific factors. This scoping review aims to identify common themes that emerge across articles, which include tools or guidance that can be used to establish whether a country is ready to deploy a new vaccine or increase uptake of an underutilised vaccine. DESIGN: Scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines. DATA SOURCES: Embase, CINAHL, Cochrane Library, Google Scholar, MEDLINE, PsycINFO and Web of Science were searched for articles published until 9 September 2023. Relevant articles were also identified through expert opinion. ELIGIBILITY CRITERIA: Articles published in any year or language that included tools or guidance to identify factors that influence a country's readiness to deploy a new or underutilised vaccine. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened records and performed data extraction. Findings were synthesised by conducting a thematic analysis. RESULTS: 38 articles met our inclusion criteria; these documents were created using methodologies including expert review panels and Delphi surveys and varied in terms of content and context-of-use. 12 common themes were identified relevant to a country's readiness to deploy a new or underutilised vaccine. These themes were as follows: (1) legal, political and professional consensus; (2) sociocultural factors and communication; (3) policy, guidelines and regulations; (4) financing; (5) vaccine characteristics and supply logistics; (6) programme planning; (7) programme monitoring and evaluation; (8) sustainable and integrated healthcare provision; (9) safety surveillance and reporting; (10) disease burden and characteristics; (11) vaccination equity and (12) human resources and training of professionals. CONCLUSIONS: This information has the potential to form the basis of a globally applicable evidence-based vaccine readiness assessment tool that can inform policy and immunisation programme decision-makers.

Current global status of male reproductive health.

BACKGROUND: The widespread interest in male reproductive health (MRH), fueled by emerging evidence, such as the global decline in sperm counts, has intensified concerns about the status of MRH. Consequently, there is a pressing requirement for a strategic, systematic approach to identifying critical questions, collecting pertinent information, and utilizing these data to develop evidence-based strategies. The methods for addressing these questions and the pathways toward their answers will inevitably vary based on the variations in cultural, geopolitical, and health-related contexts. To address these issues, a conjoint ESHRE and Male Reproductive Health Initiative (MRHI) Campus workshop was convened. OBJECTIVE AND RATIONALE: The three objectives were: first, to assess the current state of MRH around the world; second, to identify some of the key gaps in knowledge; and, third, to examine how MRH stakeholders can collaboratively generate intelligent and effective paths forward. SEARCH METHODS: Each expert reviewed and summarized the current literature that was subsequently used to provide a comprehensive overview of challenges related to MRH. OUTCOMES: This narrative report is an overview of the data, opinions, and arguments presented during the workshop. A number of outcomes are presented and can be summarized by the following overarching themes: MRH is a serious global issue and there is a plethora of gaps in our understanding; there is a need for widespread international collaborative networks to undertake multidisciplinary research into fundamental issues, such as lifestyle/environmental exposure studies, and high-quality clinical trials; and there is an urgent requirement for effective strategies to educate young people and the general public to safeguard and improve MRH across diverse population demographics and resources. LIMITATIONS REASONS FOR CAUTION: This was a workshop where worldwide leading experts from a wide range of disciplines presented and discussed the evidence regarding challenges related to MRH. While each expert summarized the current literature and placed it in context, the data in a number of areas are limited and/or sparse. Equally, important areas for consideration may have been missed. Moreover, there are clear gaps in our knowledge base, which makes some conclusions necessarily speculative and warranting of further study. WIDER IMPLICATIONS: Poor MRH is a global issue that suffers from low awareness among the public, patients, and heathcare professionals. Addressing this will require a coordinated multidisciplinary approach. Addressing the significant number of knowledge gaps will require policy makers prioritizing MRH and its funding. STUDY FUNDING/COMPETING INTERESTS: The authors would like to extend their gratitude to ESHRE for providing financial support for the Budapest Campus Workshop, as well as to Microptic S.L. (Barcelona) for kindly sponsoring the workshop. P.B. is the Director of the not-for-profit organization Global Action on Men's Health and receives fees and expenses for his work, (which includes the preparation of this manuscript). Conflicts of interest: C.J.D.J., C.L.R.B., R.A.A., P.B., M.P.C., M.L.E., N.G., N.J., C.K., AAP, M.K.O., S.R.-H., M.H.V.-L.: ESHRE Campus Workshop 2022 (Travel support-personal). C.J.D.J.: Cambridge University Press (book royalties-personal). ESHRE Annual Meeting 2022 and Yale University Panel Meeting 2023 (Travel support-personal). C.L.R.B.: Ferring and IBSA (Lecture), RBMO editor (Honorarium to support travel, etc.), ExSeed and ExScentia (University of Dundee), Bill & Melinda Gates Foundation (for research on contraception). M.P.C.: Previously received funding from pharmaceutical companies for health economic research. The funding was not in relation to this work and had no bearing on the contents of this work. No funding from other sources has been provided in relation to this work (funding was provided to his company Global Market Access Solutions). M.L.E.: Advisor to Ro, Doveras, Next, Hannah, Sandstone. C.K.: European Academy of Andrology (Past president UNPAID), S.K.: CEO of His Turn, a male fertility Diagnostic and Therapeutic company (No payments or profits to date). R.I.M.: www.healthymale.org.au (Australian Government funded not for profit in men's health sector (Employed as Medical Director 0.2 FET), Monash IVF Pty Ltd (Equity holder)). N.J.: Merck (consulting fees), Gedeon Richter (honoraria). S.R.-H.: ESHRE (Travel reimbursements). C.N.: LLC (Nursing educator); COMMIT (Core Outcomes Measures for Infertility Trials) Advisor, meeting attendee, and co-author; COMMA (Core Outcomes in Menopause) Meeting attendee, and co-author; International Federation of Gynecology and Obstetrics (FIGO) Delegate Letters and Sciences; ReproNovo, Advisory board; American Board of Urology Examiner; American Urological Association Journal subsection editor, committee member, guidelines co-author Ferring Scientific trial NexHand Chief Technology Officer, stock ownership Posterity Health Board member, stock ownership. A.P.: Economic and Social Research Council (A collaborator on research grant number ES/W001381/1). Member of an advisory committee for Merck Serono (November 2022), Member of an advisory board for Exceed Health, Speaker fees for educational events organized by Mealis Group; Chairman of the Cryos External Scientific Advisory Committee: All fees associated with this are paid to his former employer The University of Sheffield. Trustee of the Progress Educational Trust (Unpaid). M.K.O.: National Health and Medical Research Council and Australian Research Council (Funding for research of the topic of male fertility), Bill and Melinda Gates Foundation (Funding aimed at the development of male gamete-based contraception), Medical Research Future Fund (Funding aimed at defining the long-term consequences of male infertility). M.H.V.-L.: Department of Sexual and Reproductive Health and Research (SRH)/Human Reproduction Programme (HRP) Research Project Panel RP2/WHO Review Member; MRHI (Core Group Member), COMMIT (member), EGOI (Member); Human Reproduction (Associate Editor), Fertility and Sterility (Editor), AndroLATAM (Founder and Coordinator).