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Between February 2020 and May 2022, one million Americans have died of COVID-19. To determine the contribution of those deaths to all-cause mortality in terms of life expectancy reductions and the resulting economic welfare losses, we calculated their combined impact on national income growth and the added value of lives lost. We estimated that US life expectancy at birth dropped by 3.08 years due to the million COVID-19 deaths. Economic welfare losses estimated in terms of national income growth supplemented by the value of lives lost, was in the order of US$3.57 trillion. US$2.20 trillion of these losses were in in the non-Hispanic White population (56.50%), US$698.24 billion (19.54%) in the Hispanic population, and US$579.93 billion (16.23%) in the non-Hispanic Black population. The scale of life expectancy and welfare losses underscores the pressing need to invest in health in the US to prevent further economic shocks from future pandemic threats.

Summary Background The tuberculosis targets for the UN Sustainable Development Goals (SDGs) call for a 90% reduction in tuberculosis deaths by 2030, compared with 2015, but meeting this target now seems highly improbable. To assess the economic impact of not meeting the target until 2045, we estimated full-income losses in 120 countries, including those due to excess deaths resulting from COVID-19-related disruptions to tuberculosis services, for the period 2020–50. Methods Annual mortality risk changes at each age in each year from 2020 to 2050 were estimated for 120 countries. This risk change was then converted to full-income risk by calculating a population-level mortality risk change and multiplying it by the value of a statistical life-year in each country and year. As a comparator, we assumed that current rates of tuberculosis continue to decline through the period of analysis. We calculated the full-income losses, and mean life expectancy losses per person, at birth and at age 35 years, under scenarios in which the SDG targets are met in 2030 and in 2045. We defined the cost of inaction as the difference in full-income losses and tuberculosis mortality between these two scenarios. Findings From 2020 to 2050, based on the current annual decrease in tuberculosis deaths of 2%, 31·8 million tuberculosis deaths (95% uncertainty interval 25·2 million–39·5 million) are estimated to occur, corresponding to an economic loss of US$17·5 trillion (14·9 trillion–20·4 trillion). If the SDG tuberculosis mortality target is met in 2030, 23·8 million tuberculosis deaths (18·9 million–29·5 million) and $13·1 trillion (11·2 trillion–15·3 trillion) in economic losses can be avoided. If the target is met in 2045, 18·1 million tuberculosis deaths (14·3 million–22·4 million) and $10·2 trillion (8·7 trillion–11·8 trillion) can be avoided. The cost of inaction of not meeting the SDG tuberculosis mortality target until 2045 (vs 2030) is, therefore, 5·7 million tuberculosis deaths (5·1 million–8·1 million) and $3·0 trillion (2·5 trillion–3·5 trillion) in economic losses. COVID-19-related disruptions add $290·3 billion (260·2 billion–570·1 billion) to this cost. Interpretation Failure to achieve the SDG tuberculosis mortality target by 2030 will lead to profound economic and health losses. The effects of delay will be greatest in sub-Saharan Africa. Affected countries, donor nations, and the private sector should redouble efforts to finance tuberculosis programmes and research because the economic dividend of such strategies is likely to be substantial. Funding None.

Health and economic benefits possible with emerging tuberculosis vaccines are not fully known. We estimated gains possible with novel post-exposure vaccines, in India and Indonesia. We modeled vaccine impact on TB incidence, TB mortality, and on national income growth and the intrinsic value of living longer, known as Full-income. We considered several vaccine efficacies, initiation and scale-up scenarios. We found that if all age groups are vaccinated in 2025, then 2.3 million TB deaths in India and 695,000 TB deaths in Indonesia can be prevented, adding 0.09 years and 0.17 years to individual life expectancy at birth, on average annually. Full-income savings is US$2 trillion in India and US$680 billion in Indonesia. Even if delayed until 2030, 1.6 million deaths in India and 489,000 deaths in Indonesia can be prevented, with full-income savings of US$1.5 trillion and US$490 billion. These benefits suggest that further investment in the vaccines is prudent.Significance Statement There are no prior economic evaluations of candidate tuberculosis vaccines. Our study addresses this gap to answer two questions: (1) is there value in making the vaccine available given the efficacies demonstrated to date; and (2) is there an optimal time window for making the vaccine available. The conclusions in relation to these two questions are important because: (1) they are based on findings from two countries, which jointly account for 35% of global TB incidence and 38.8% of global TB mortality in 2019; (2) they provide guidance for future investment in the vaccine and roll-out in those countries.

Summary box The COVID-19 crisis has led to rapidly changing working patterns for many people, including new forms of remote working, flexible working, social distancing at work and shift work. Unfortunately, COVID-19 has also exposed profound inequities in workplace health risks; those working lower paid jobs carrying the greatest risk. In particular, this pandemic has also shone a light on the problem of presenteeism, that is, the phenomenon of people working when they are sick.1 Here, we outline why presenteeism is such an important global …

Background: A recent phase 2b trial of the M72/AS01E candidate tuberculosis vaccine demonstrated 49.7%-54.1% protection against progression from latent to active pulmonary tuberculosis in populations previously unexposed to HIV. To determine if investment in a phase 3 trial is justifiable, epidemiological and economic impacts in India and Indonesia were estimated. Methods: Vaccine impact was modeled using a deterministic, age structured TB transmission dynamics model, for efficacies 49.7% and 54.1% and duration of protection lasting lifetime or 10 years. Economic impact was estimated from 2020 to 2050, in terms of full-income, based on annual mortality risk reductions, using the value-of-a-statistical-life year in each country. Impact on cause-eliminated life expectancy was additionally calculated. Results: In India, 53.8 million incident cases can give rise to 8.8 million TB deaths and US$6.6 trillion in economic losses; in Indonesia, to 23.3 million incident cases, 3.2 million TB deaths and US$2.9 trillion in economic losses. Vaccination, if initiated in 2025 to the 18-49 year old population, reduces 19% of TB deaths in India and 12% of TB deaths in Indonesia, contributing to 22.5% and 12.9% reductions in economic losses, respectively. Vaccinating populations of all ages, reduces 25.8% of TB deaths in India and 21.5% of TB deaths in Indonesia, with 30.3% and 23% reductions in economic losses, respectively. Delaying vaccination until 2030, to the 18-49 year old population, reduces 12.8% and 8% of TB deaths, with 16% and 8.8% reductions in economic losses. By extending vaccination to populations of all ages, 18.2% and 15.1% of TB deaths and 22.6% and 16.6% in economic losses, can be averted. In the best case, vaccination can prevent 27.5% and 20.7% of life expectancy losses at birth, respectively. Interpretation: If up to a third of economic losses and a quarter of TB deaths in India, and a quarter of TB deaths and economic losses in Indonesia can be averted, then investment in a phase 3 trial is a worthy consideration. Longer-term economic gains are potentially even larger, given the impact on life expectancy in peak productive ages. The window for realizing these gains is fast approaching. Funding Statement: SFA and LJA: NPRP grant number 7-627-3-167 from the Qatar National Research Fund (a member of 29 Qatar Foundation) Declaration of Interests: We declare that we have no conflicts of interest.

Background: Meeting the End TB mortality target by 2030, a 90% reduction compared to 2015 levels seems increasingly improbable. To assess the economic impact of not meeting the End TB mortality target by 2030, and alternatively 2045, a full income economic analysis was performed, using data from 120 countries. Methods: Mortality risk reductions were calculated based on the End TB mortality target being met in 2030 and 2045. The annual mortality risk change at each age interval, was converted into full-income risk, multiplying the rescaled population mortality risk change by the value-of-a-statistical-life year, computed as a proportion of Gross Domestic Product (GDP). The Cost of Inaction was calculated as the difference in full-income losses if the End TB target is met in 2030 compared to 2045. Impact on life expectancies, at birth and at age 35, were also estimated for these different end dates. Results: From 2020 to 2050, based on current trends, there would be 31.8 million TB deaths and full-income losses amounting to US$17.5 trillion (mean=US$230 million; SD=US$26 billion). If the End TB mortality target is met in 2030, US$13.2 trillion of the losses can be avoided. If met in 2045, US$10.2 trillion can be avoided. The additional cost of not meeting the End TB target until 2045 would be 5.7 million deaths and US$2.96 trillion in economic losses. Interpretation: Failure to achieve the End TB mortality target by 2030 will lead to profound full-income losses. The impact of delay will be greatest in sub-Saharan Africa where full-income losses in 15 countries will contribute more than 10% of annual GDP reduction. Impacted countries, donor nations and the private sector should redouble efforts to finance TB programs and research, since the economic dividend of such strategies is likely to be profound. Funding Statement: This analysis was undertaken without extramural funding. Declaration of Interests: The authors declare that we have no conflicts of interest.

Summary Development assistance for health (DAH), the value of which peaked in 2013 and fell in 2015, is unlikely to rise substantially in the near future, increasing reliance on domestic and innovative financing sources to sustain health programmes in low-income and middle-income countries. We examined innovative financing instruments (IFIs)—financing schemes that generate and mobilise funds—to estimate the quantum of financing mobilised from 2002 to 2015. We identified ten IFIs, which mobilised US$8·9 billion (2·3% of overall DAH) in 2002–15. The funds generated by IFIs were channelled mostly through GAVI and the Global Fund, and used for programmes for new and underused vaccines, HIV/AIDS, malaria, tuberculosis, and maternal and child health. Vaccination programmes received the largest amount of funding ($2·6 billion), followed by HIV/AIDS ($1080·7 million) and malaria ($1028·9 million), with no discernible funding targeted to non-communicable diseases.

Background Accurate estimates of the burden of antimicrobial resistance (AMR) are needed to establish the magnitude of this global threat in terms of both health and cost, and to paramaterise cost-effectiveness evaluations of interventions aiming to tackle the problem. This review aimed to establish the alternative methodologies used in estimating AMR burden in order to appraise the current evidence base. Methods MEDLINE, EMBASE, Scopus, EconLit, PubMed and grey literature were searched. English language studies evaluating the impact of AMR (from any microbe) on patient, payer/provider and economic burden published between January 2013 and December 2015 were included. Independent screening of title/abstracts followed by full texts was performed using pre-specified criteria. A study quality score (from zero to one) was derived using Newcastle-Ottawa and Philips checklists. Extracted study data were used to compare study method and resulting burden estimate, according to perspective. Monetary costs were converted into 2013 USD. Results Out of 5187 unique retrievals, 214 studies were included. One hundred eighty-seven studies estimated patient health, 75 studies estimated payer/provider and 11 studies estimated economic burden. 64% of included studies were single centre. The majority of studies estimating patient or provider/payer burden used regression techniques. 48% of studies estimating mortality burden found a significant impact from resistance, excess healthcare system costs ranged from non-significance to $1 billion per year, whilst economic burden ranged from $21,832 per case to over $3 trillion in GDP loss. Median quality scores (interquartile range) for patient, payer/provider and economic burden studies were 0.67 (0.56-0.67), 0.56 (0.46-0.67) and 0.53 (0.44-0.60) respectively. Conclusions This study highlights what methodological assumptions and biases can occur dependent on chosen outcome and perspective. Currently, there is considerable variability in burden estimates, which can lead in-turn to inaccurate intervention evaluations and poor policy/investment decisions. Future research should utilise the recommendations presented in this review. Trial registration This systematic review is registered with PROSPERO (PROSPERO CRD42016037510). Electronic supplementary material The online version of this article (10.1186/s13756-018-0336-y) contains supplementary material, which is available to authorized users.

By 2015, around 15 million individuals were accessing life–saving antiretroviral treatment (ART) [1]. Yet, the “AIDS transition” [2] is not in sight–in 2014, there were 36.9 million people living with HIV, 2 million new HIV infections and 1.2 million AIDS–related deaths [3]. The continuing HIV epidemic requires sustained investment to prevent new infections and to provide treatment to those who need ART now and in the future. However, as more individuals access ART, domestic obligations for financing HIV will increase, reaching an estimated US$ 190 billion between 2015 and 2050 and account for as high as 47% of the GDP in high prevalence sub–Saharan African countries such as Malawi [4], creating long term commitments that have to be met. The financial obligations have major implications for the affected countries and donors–not just in economic terms, but also in the way they manage financing of the HIVresponse, which requires empowering countries to take greater responsibility for managing funds from all sources. The return of investment in HIV response as measured by benefit to cost ratio has been estimated at 280% [5], with substantial economic, social and health benefits reported by other studies [6], comparable to benefit to cost ratios reported for maternal and child health investments [7]. However, donor financing, which accounts for a large share of the HIV/AIDS funding in sub–Saharan Africa, is constrained due to the global economic crisis [8]. Domestic financing remains equally challenging, especially in high–prevalence low–income countries that are fiscally constrained. Compounding the financing challenges are inefficiencies in channeling and use of available funds, and the harmful asymmetry between the long–term financing needs for HIV and short–term replenishment cycles of donor institutions [9]. There are opportunities for increasing HIV financing, however. African economies are enjoying economic growth [10]. There are also untapped natural resources that could generate upwards of US$ 4 billion each year [11]. Additional fiscal space could be created in domestic budgets by improving efficiency in allocation both to and within HIV programmes and by co–financing HIV services with funding other economic sectors [12]. Innovative financing could offer new sources of funding. Conceived as a funding source to meet the Millennium Development Goals (MDGs), innovative financing, which provided around US$ 6 billion in total in 2002–2012 [13], is increasingly an important source of funding for global health [14]. We explore how innovative financing could be used to co–finance the long–term HIV obligations by augmenting domestic contributions in sub–Saharan Africa. We analyze how different innovative financing instruments can be operationalised and the institutional arrangements needed for their effective use.

Objectives To estimate the present value of current and future funding needed for HIV treatment and prevention in 9 sub-Saharan African (SSA) countries that account for 70% of HIV burden in Africa under different scenarios of intervention scale-up. To analyse the gaps between current expenditures and funding obligation, and discuss the policy implications of future financing needs. Design We used the Goals module from Spectrum, and applied the most up-to-date cost and coverage data to provide a range of estimates for future financing obligations. The four different scale-up scenarios vary by treatment initiation threshold and service coverage level. We compared the model projections to current domestic and international financial sources available in selected SSA countries. Results In the 9 SSA countries, the estimated resources required for HIV prevention and treatment in 2015–2050 range from US$98 billion to maintain current coverage levels for treatment and prevention with eligibility for treatment initiation at CD4 count of

Objective.— To determine the efficacy of occipital nerve blocks using reconstituted botulinum toxin type-A (BTX-A) in providing significant and prolonged pain relief in chronic occipital neuralgia. Background.— Occipital neuralgia is a unilateral or bilateral radiating pain with paresthesias commonly manifesting as paroxysmal episodes and involving the occipital and parietal regions. Common causes of occipital neuralgia include irritation or injury to the divisions of the occipital nerve, myofascial spasm, and focal entrapment of the occipital nerve. Treatment options include medication therapy, occipital nerve blocks, and surgical techniques. BTX-A, which has shown promise in relief of other headache types, may prove a viable therapeutic option for occipital neuralgia pain. Methods.— Botulinum toxin type-A (reconstituted in 3 cc of saline) was injected into regions traversed by the greater and lesser occipital nerve in 6 subjects diagnosed with occipital neuralgia. Subjects were instructed to report their daily pain level (on a visual analog pain scale), their ability to perform daily activities (on several quality of life instruments) and their daily pain medication usage (based on a self-reported log), 2 weeks prior to the injection therapy and 12 weeks following injection therapy. Data were analyzed for significant variation from baseline values. Results.— The dull/aching and pin/needles types of pain reported by the subjects did not show a statistically significant improvement during the trial period. The sharp/shooting type of pain, however, showed improvement during most of the trial period except weeks 3-4 and 5-6. The quality of life measures exhibited some improvement. The headache-specific quality of life measure showed significant improvement by 6 weeks which continued through week 12. The general health- and depression-related measures showed no statistical improvement. No significant reduction in pain medication usage was demonstrated. Conclusions.— Our results indicate that BTX-A improved the sharp/shooting type of pain most commonly known to be associated with occipital neuralgia. Additionally, the quality of life measures assessing burden and long-term impact of the headaches, further corroborated improvement seen in daily head pain.