Regression Correction Equation to Adjust Serum Iron and Ferritin Concentrations Based on C-Reactive Protein and Albumin in Patients Receiving Primary and Secondary Care.

BACKGROUND: Systemic inflammation, even at low levels, can greatly interfere with measures of iron status, making diagnosis of iron deficiency difficult. The objective of the present study was to create linear regression correction equations to adjust serum ferritin and iron concentrations based on measurements of the acute-phase proteins C-reactive protein (CRP) and albumin. METHODS: Data from a cohort (1) of patients (n = 7226) in primary and secondary care who had serum ferritin, iron, CRP, and albumin measured at the same time point were examined. Linear regression coefficients were calculated for CRP and albumin with serum iron and ferritin as the outcome variables. Patients with ferritin <15 µg/L or serum iron <10 µmol/L were categorized as iron deficient. The equation was then applied to a cohort (2) of patients with colorectal cancer who had ferritin and iron measured preoperatively ( n = 356). RESULTS: In cohort 1 there was a significant difference in the proportions of patients with serum ferritin <15 µg/L and serum iron <10 µmol/L, respectively, when the unadjusted (7% and 55%), adjusted based on CRP alone (13% and 26%), adjusted based on albumin alone (11% and 37%), and adjusted based on both CRP and albumin (24% and 15%) values were compared (both P < 0.001). In cohort 2 there was a significant difference in the proportions of patients with serum ferritin <15 µg/L and serum iron <10 µmol/L, respectively, when the unadjusted (28% and 66%), adjusted based on CRP alone (39% and 57%), adjusted based on albumin alone (39% and 59%), and adjusted based on both CRP and albumin (46% and 44%) values were compared (P < 0.001 and P < 0.004). CONCLUSIONS: In both cohorts the greatest increase in the proportion of patients meeting definitions of iron deficiency was found when adjustment was made for both CRP and albumin together. Even low levels of inflammation had a significant effect on serum iron and ferritin values.

Cost of implementing a doxycycline test-and-treat strategy for onchocerciasis elimination among settled and semi-nomadic groups in Cameroon.

BACKGROUND: Onchocerciasis is a neglected tropical disease with 217.5 million people globally at risk of having the infection. In both settled and semi-nomadic communities of Massangam Health District in Cameroon, Sightsavers has been carrying out test-and-treat with doxycycline and twice-yearly ivermectin distribution. This paper focuses on the cost of test-and-treat with doxycycline in the two community contexts of settled and semi-nomadic. METHODS: For the valuation, a combination of gross or micro-costing was used to identify cost components, as well as bottom-up and top-down approaches. The opportunity costs of vehicle and equipment use were estimated and included. Not included, however, were the opportunity costs of building use and Ministry of Public Health staff salaries. We only captured the incremental costs of implementing test-and-treat activities as part of a functional annual community-directed treatment with the ivermectin programme. RESULTS: We estimate the economic cost per person tested and cost per person treated in Massangam to be US$135 and US$667 respectively. Total implementation cost in the settled community was US$79,409, and in the semi-nomadic community US$69,957. Overall, the total economic cost of implementing the doxycycline test-and-treat strategy for onchocerciasis elimination in Massangam came to US$168,345. Financial costs represented 91% of total costs. CONCLUSIONS: Unit costs of test-and-treat in both settled and semi-nomadic communities are higher than unit costs of community-directed treatment with ivermectin. However, it is critical to note that a two-year implementation shows a significantly larger reduction in infection prevalence than the preceding 20 years of annual community-directed treatment with ivermectin. Test-and-treat with doxycycline may be a cost-effective intervention in places where the prevalence of microfilaria is still high, or in hard-to-reach areas where community-directed treatment with ivermectin and MDA coverage are not high enough to stop transmission or where marginalised populations consistently miss treatment.

Delivering universal eye health coverage: a call for more and better eye health funding.

Additional resources are urgently needed to tackle the increasing burden of vision impairment, to support the delivery of the Sustainable Development Goals, and to live up to the promise to leave no one behind. This commentary reflects on eye health funding in developing economies and calls for a step change in delivering more and better financing and the integration of eye health into universal health coverage. The transformation in funding will need to be done carefully, creatively and collaboratively to ensure that funding results in faster and more sustainable delivery of high quality, affordable eye healthcare for all.

Leveraging resources and the impact of neglected tropical disease elimination programmes: getting (much) more than what you pay for.

Partnerships have been key to significant progress in combating neglected tropical diseases (NTDs). Collaboration between a range of partners, each bringing different skills and resources, helps reach more people in need with greater efficiency. Some partners have contributed in-kind donations, including drugs and volunteer time. When making resource allocation decisions donors need to consider the significant leverage their investment in NTD programmes can have. This commentary estimates the value of the leverage that the Ascend programme achieved. It is clear that funding from UK aid to Ascend delivered (much) more than what they paid for.

Measuring equity of access to eye health outreach camps in rural Malawi.

INTRODUCTION: Equity in the access and use of health services is critical if countries are to make progress towards universal health coverage and address the systematic exclusion of the most vulnerable groups. The purpose of this study was to assess if the Co-ordinated Approach To Community Health programme implemented by Sightsavers was successful in reaching the poorest population, women, and people living with disabilities in Kasungu district, Malawi. METHODS: Between April and September 2017, data on socio-economic status, household characteristics and functional disability were collected from patients attending at eye camps in Kasungu district, Malawi. Using asset-based tools to measure household wealth (EquityTool© and Simple Poverty Scorecard©) and the Washington Group Short Set of Questions, individuals were categorised by wealth quintiles, poverty status, and functional disability status and then compared to relevant representative national household surveys. In addition, a follow-up household survey was conducted to check the validity of self-reported household characteristics at eye camps. RESULTS: A total of 1,358 individuals participated in the study. The study shows that self-reported data on household characteristics and assets are reliable and can be collected in clinical settings (instead of relying on direct observations of assets). Individuals attending outreach camps were poorer in terms of relative wealth and absolute poverty rates compared to the rest of the population in Kasungu. It was estimated that 9% of the participants belonged to the poorest quintile compared to 4% for the population in Kasungu (DHS 2015-2016). The ultra-poverty rate was also lower among respondents (13%) compared to 15% for Kasungu district (IHS 2017). The functional disability rate was 27.5% for study participants, and statistically higher than the general population (5.6%, SENTIF 2017). Even though women are more at risks than men, 54% of the participants were men. CONCLUSIONS: Our study shows that existing tools can be reliably used, and combined, if based on recent population data, to assess equity of access to health services for vulnerable groups of the population. The findings suggest that the programme was successful in reaching the poorest people of the Kasungu district population as well as those with disabilities through outreach camps but that more men than women were reach through the programme. Subsequently, our study showed that self-reported household characteristics are a reliable method to measure asset-based wealth of camps' attendee. However, it is essential to use sub-national data (district or regional level) from recent surveys for the purpose of benchmarking in order to produce accurate results.

Navigating the way to onchocerciasis elimination: the feasibility and affordability of Onchocerciasis Elimination Mapping.

BACKGROUND: Onchocerciasis is targeted for elimination of transmission by 2030 in at least 21 countries. To achieve this, recent and accurate data on the extent and intensity of onchocerciasis transmission are required. This will include mapping areas previously unassessed, or remapping of areas that were last visited as part surveys aiming to prevent blindness, not assess transmission in totality. There is near universal acceptance of the need to carry out these mapping reassessments, to achieve equitable and lasting elimination of onchocerciasis transmission. However, there is no consensus on how to conduct onchocerciasis elimination mapping (OEM), and little published data to inform policymakers and programme managers, including on cost. METHODS: Here, we summarise the methods and cost implications of conducting pilot OEM surveys in Ghana and Nigeria in 2018. We have included a breakdown of costs incurred overall, per person and per implementation unit in each country, as well as detailed analysis of the cost categories and the main cost drivers. RESULTS: The procurement and logistics of diagnostics accounted for more than one-third of the total cost, a significant cost driver. CONCLUSIONS: This information will be valuable to policymakers and donors as they seek to prioritise onchocerciasis elimination and plan to complete OEM.

The economics of vision impairment and its leading causes: A systematic review.

Vision impairment (VI) can have wide ranging economic impact on individuals, households, and health systems. The aim of this systematic review was to describe and summarise the costs associated with VI and its major causes. We searched MEDLINE (16 November 2019), National Health Service Economic Evaluation Database, the Database of Abstracts of Reviews of Effects and the Health Technology Assessment database (12 December 2019) for partial or full economic evaluation studies, published between 1 January 2000 and the search dates, reporting cost data for participants with VI due to an unspecified cause or one of the seven leading causes globally: cataract, uncorrected refractive error, diabetic retinopathy, glaucoma, age-related macular degeneration, corneal opacity, trachoma. The search was repeated on 20 January 2022 to identify studies published since our initial search. Included studies were quality appraised using the British Medical Journal Checklist for economic submissions adapted for cost of illness studies. Results were synthesized in a structured narrative. Of the 138 included studies, 38 reported cost estimates for VI due to an unspecified cause and 100 reported costs for one of the leading causes. These 138 studies provided 155 regional cost estimates. Fourteen studies reported global data; 103/155 (66%) regional estimates were from high-income countries. Costs were most commonly reported using a societal (n = 48) or healthcare system perspective (n = 25). Most studies included only a limited number of cost components. Large variations in methodology and reporting across studies meant cost estimates varied considerably. The average quality assessment score was 78% (range 35-100%); the most common weaknesses were the lack of sensitivity analysis and insufficient disaggregation of costs. There was substantial variation across studies in average treatment costs per patient for most conditions, including refractive error correction (range $12-$201 ppp), cataract surgery (range $54-$3654 ppp), glaucoma (range $351-$1354 ppp) and AMD (range $2209-$7524 ppp). Future cost estimates of the economic burden of VI and its major causes will be improved by the development and adoption of a reference case for eye health. This could then be used in regular studies, particularly in countries with data gaps, including low- and middle-income countries in Asia, Eastern Europe, Oceania, Latin America and sub-Saharan Africa.

"More money for health - more health for the money": a human resources for health perspective.

BACKGROUND: At the MDG Summit in September 2010, the UN Secretary-General launched the Global Strategy for Women's and Children's Health. Central within the Global Strategy are the ambitions of "more money for health" and "more health for the money". These aim to leverage more resources for health financing whilst simultaneously generating more results from existing resources - core tenets of public expenditure management and governance. This paper considers these ambitions from a human resources for health (HRH) perspective. METHODS: Using data from the UK Department for International Development (DFID) we set out to quantify and qualify the British government's contributions on HRH in developing countries and to establish a baseline.. To determine whether activities and financing could be included in the categorisation of 'HRH strengthening' we adopted the Agenda for Global Action on HRH and a WHO approach to the 'working lifespan' of health workers as our guiding frameworks. To establish a baseline we reviewed available data on Official Development Assistance (ODA) and country reports, undertook a new survey of HRH programming and sought information from multilateral partners. RESULTS: In financial year 2008/9 DFID spent £901 million on direct 'aid to health'. Due to the nature of the Creditor Reporting System (CRS) of the Organisation for Economic Co-operation and Development (OECD) it is not feasible to directly report on HRH spending. We therefore employed a process of imputed percentages supported by detailed assessment in twelve countries. This followed the model adopted by the G8 to estimate ODA on maternal, newborn and child health. Using the G8's model, and cognisant of its limitations, we concluded that UK 'aid to health' on HRH strengthening is approximately 25%. CONCLUSIONS: In quantifying DFID's disbursements on HRH we encountered the constraints of the current CRS framework. This limits standardised measurement of ODA on HRH. This is a governance issue that will benefit from further analysis within more comprehensive programmes of workforce science, surveillance and strategic intelligence. The Commission on Information and Accountability for Women's and Children's Health may present an opportunity to partially address the limitations in reporting on ODA for HRH and present solutions to establish a global baseline.

Global economic productivity losses from vision impairment and blindness.

BACKGROUND: In the absence of accessible, good quality eye health services and inclusive environments, vision loss can impact individuals, households and communities in many ways, including through increased poverty, reduced quality of life and reduced employment. We aimed to estimate the annual potential productivity losses associated with reduced employment due to blindness and moderate and severe vision impairment (MSVI) at a regional and global level. METHODS: We constructed a model using the most recent economic, demographic (2018) and prevalence (2020) data. Calculations were limited to the working age population (15-64 years) and presented in 2018 US Dollars purchasing power parity (ppp). Two separate models, using Gross Domestic Product (GDP) and Gross National Income (GNI), were calculated to maximise comparability with previous estimates. FINDINGS: We found that 160.7 million people with MSVI or blindness were within the working age and estimated that the overall relative reduction in employment by people with vision loss was 30.2%. Globally, using GDP we estimated that the annual cost of potential productivity losses of MSVI and blindness was $410.7 billion ppp (range $322.1 - $518.7 billion), or 0.3% of GDP. Using GNI, overall productivity losses were estimated at $408.5 billion ppp (range $320.4 - $515.9 billion), 0.5% lower than estimates using GDP. INTERPRETATION: These findings support the view that blindness and MSVI are associated with a large economic impact worldwide. Reducing and preventing vision loss and developing and implementing strategies to help visually impaired people to find and keep employment may result in significant productivity gains. FUNDING: MJB is supported by the Wellcome Trust (207472/Z/17/Z). JR's appointment at the University of Auckland is funded by the Buchanan Charitable Foundation, New Zealand. The Lancet Global Health Commission on Global Eye Health was supported by grants from The Queen Elizabeth Diamond Jubilee Trust, Moorfields Eye Charity (GR001061), NIHR Moorfields Biomedical Research Centre, The Wellcome Trust, Sightsavers, The Fred Hollows Foundation, The SEVA Foundation, The British Council for the Prevention of Blindness and Christian Blind Mission. The funders had no role in the design, conduct, data analysis of the study, or writing of the manuscript.

What next after GDP-based cost-effectiveness thresholds?

Public payers around the world are increasingly using cost-effectiveness thresholds (CETs) to assess the value-for-money of an intervention and make coverage decisions. However, there is still much confusion about the meaning and uses of the CET, how it should be calculated, and what constitutes an adequate evidence base for its formulation. One widely referenced and used threshold in the last decade has been the 1-3 GDP per capita, which is often attributed to the Commission on Macroeconomics and  WHO guidelines on Choosing Interventions that are Cost Effective (WHO-CHOICE). For many reasons, however, this threshold has been widely criticised; which has led experts across the world, including the WHO, to discourage its use. This has left a vacuum for policy-makers and technical staff at a time when countries are wanting to move towards Universal Health Coverage . This article seeks to address this gap by offering five practical options for decision-makers in low- and middle-income countries that can be used instead of the 1-3 GDP rule, to combine existing evidence with fair decision-rules or develop locally relevant CETs. It builds on existing literature as well as an engagement with a group of experts and decision-makers working in low, middle and high income countries.

The Importance of Failure: How Doing Impact Surveys That Fail Saves Trachoma Programs Money.

Trachoma programs use annual antibiotic mass drug administration (MDA) in evaluation units (EUs) that generally encompass 100,000-250,000 people. After one, three, or five MDA rounds, programs undertake impact surveys. Where impact survey prevalence of trachomatous inflammation-follicular (TF) in 1- to 9-year-olds is ≥ 5%, ≥ 1 additional MDA rounds are recommended before resurvey. Impact survey costs, and the proportion of impact surveys returning TF prevalence ≥ 5% (the failure rate or, less pejoratively, the MDA continuation rate), therefore influence the cost of eliminating trachoma. We modeled, for illustrative EU sizes, the financial cost of undertaking MDA with and without conducting impact surveys. As an example, we retrospectively assessed how conducting impact surveys affected costs in the United Republic of Tanzania for 2017-2018. For EUs containing 100,000 people, the median (interquartile range) cost of continuing MDA without doing impact surveys is USD 28,957 (17,581-36,197) per EU per year, whereas continuing MDA solely where indicated by impact survey results costs USD 17,564 (12,158-21,694). If the mean EU population is 100,000, then continuing MDA without impact surveys becomes advantageous in financial cost terms only when the continuation rate exceeds 71%. For the United Republic of Tanzania in 2017-2018, doing impact surveys saved enough money to provide MDA for > 1,000,000 people. Although trachoma impact surveys have a nontrivial cost, they generally save money, providing EUs have > 50,000 inhabitants, the continuation rate is not excessive, and they generate reliable data. If all EUs pass their impact surveys, then we have waited too long to do them.

Estimating the global cost of vision impairment and its major causes: protocol for a systematic review.

INTRODUCTION: Vision impairment (VI) places a burden on individuals, health systems and society in general. In order to support the case for investing in eye health services, an updated cost of illness study that measures the global impact of VI is necessary. To perform such a study, a systematic review of the literature is needed. Here we outline the protocol for a systematic review to describe and summarise the costs associated with VI and its major causes. METHODS AND ANALYSIS: We will systematically search in Medline (Ovid) and the Centre for Reviews and Dissemination database which includes the National Health Service Economics Evaluation Database. No language or geographical restriction will be applied. Additional literature will be identified by reviewing the references in the included studies and by contacting field experts. Grey literature will be considered. The review will include any study published from 1 January 2000 to November 2019 that provides information about costs of illness, burden of disease and/or loss of well-being in participants with VI due to an unspecified cause or due to one of the seven leading causes globally.Two reviewers will independently screen studies and extract relevant data from included studies. Methodological quality of economic studies will be assessed based on the British Medical Journal checklist for economic submissions adapted to costs of illness studies. This protocol has been prepared following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis protocols and has been published prospectively in Open Science Framework. ETHICS AND DISSEMINATION: Formal ethical approval is not required, as primary data will not be collected in this review. The findings of this study will be disseminated through peer-reviewed publications, stakeholder meetings and inclusion in the ongoing Lancet Global Health Commission on Global Eye Health. REGISTRATION DETAILS: https://osf.io/9au3w (DOI 10.17605/OSF.IO/6F8VM).

Strengthening the links between mapping, planning and global engagement for disease elimination: lessons learnt from trachoma.

BACKGROUND: Trachoma is the leading infectious cause of blindness. Until recently, reliable data on the global extent of the disease, detailed plans for elimination, and government, donor and partner engagement were all inadequate. METHODS: The trachoma community undertook a systematic, three-pronged strategy to map trachoma district by district, develop national-level trachoma elimination plans, and create a framework for governments, donors and partners to convene and coordinate in support of trachoma elimination.  RESULT: There has been a frame-shift in internal and external perceptions of the global trachoma programme, from being an effort working towards disease control in focussed geographical areas, to one in the process of achieving worldwide disease elimination. Multiple factors contributed to the successful implementation of mapping, planning, and cross-sectional engagement of governments, partners and donors. CONCLUSIONS: Elimination of trachoma is possible if the right combination of factors is in place. Planning for success is a critical first step. Some remaining challenges must still be addressed if the elimination targets are to be successfully attained.

Quantitative data on the magnitude of the systemic inflammatory response and its relationship with serum measures of iron status.

The present study aimed to quantify the magnitude of the systemic inflammatory response, measured by C-reactive protein (CRP) and albumin, and its relationship with common serum biochemical measures of iron status including total iron, transferrin, transferrin saturation, and ferritin. Retrospective interrogation of laboratory computer databases at 4 centers between 2006 and 2011 provided results from patients in which serum CRP and albumin had been measured together with iron studies (iron, transferrin, and transferrin saturation, n = 16,522) and ferritin (n = 7,226). Analyte results were categorized into groups according to CRP and albumin. When those groups with CRP <10 mg/L and albumin >35 g/L, CRP 11-80 mg/L and albumin 25-35 mg/L, and CRP >80 mg/L and albumin <25 g/L were compared, the median serum total iron was 15.0, 7.0, and 3.0 µmol/L, respectively (P < 0.001), an overall reduction of 80%. The median serum transferrin concentration was 2.6, 2.0, and 1.3 µmol/L respectively (P < 0.001), an overall reduction of 50%. The median transferrin saturation was 23%, 13%, and 10% respectively (P < 0.001), an overall reduction of 56%. The median serum ferritin was 77, 173, and 445 µg/L respectively (P < 0.001), an overall increase of 578%. The present study quantifies the impact of the systemic inflammatory response on serum measures of iron status. This association should be taken into account when measures of iron status are requested and interpreted to prevent misdiagnosis.

A new method for the measurement of lysosomal acid lipase in dried blood spots using the inhibitor Lalistat 2.

BACKGROUND: Cholesterol ester storage disease (CESD) and Wolman Disease (WD) are due to deficiency of lysosomal acid lipase (LAL). A new method is described for the measurement of LAL in dried blood spots (DBS) using Lalistat 2 an inhibitor of LAL. METHODS: LAL activity in DBS extracts was measured using the substrate 4-methylumbelliferyl palmitate. LAL activity was determined by measuring total lipase activity and lipase activity in the presence of Lalistat 2. The specificity of Lalistat 2 was investigated using human recombinant LAL (hrLAL) and human pancreatic lipase (hPL). RESULTS: Lalistat 2 inhibited hrLAL with 1% residual activity at 1 µM inhibitor but had no effect on hPL up to 10 µM. LAL activity in DBS samples obtained from normal controls (n=140) was 0.50-2.30 nmol/punch/h and in patients with CESD was <0.03 nmol/punch/h (n=11). Activity in carriers showed intermediate activity: 0.15-0.40 nmol/punch/h (n=15). CONCLUSIONS: Measurement of LAL using DBS is made difficult by the presence of other lipases in whole blood. Lalistat 2 is a specific inhibitor of LAL which allows the determination of LAL in DBS. Results show the method differentiates clearly between normal controls, carriers and affected cases.

Intrathecal drug delivery for management of cancer and noncancer pain.

Intrathecal drug delivery (ITDD) has been an option for the management of persistent pain since the 1980s. The discovery of opioid receptors in the central nervous system was the impetus for early attempts to deliver opioids intraspinally. Approximately, 10-20 percent patients with cancer pain get inadequate analgesia from conventional medical management; this group particularly may benefit from ITDD. However, there is also some evidence for the use of ITDD in those with noncancer pain. This review presents options for ITDD, available drugs, evidence for efficacy, principles of patient selection, and problems with the intrathecal route.