Measuring Zero-Dose Children: Reflections on Age Cohort Flexibilities for Targeted Immunization Surveys at the Local Level.

Zero-dose (ZD) children is a critical objective in global health, and it is at the heart of the Immunization Agenda 2030 (IA2030) strategy. Coverage for the first dose of diphtheria-tetanus-pertussis (DTP1)-containing vaccine is the global operational indicator used to estimate ZD children. When surveys are used, DTP1 coverage estimates usually rely on information reported from caregivers of children aged 12-23 months. It is important to have a global definition of ZD children, but learning and operational needs at a country level may require different ZD measurement approaches. This article summarizes a recent workshop discussion on ZD measurement for targeted surveys at local levels related to flexibilities in age cohorts of inclusion from the ZD learning Hub (ZDLH) initiative-a learning initiative involving 5 consortia of 14 different organizations across 4 countries-Bangladesh, Mali, Nigeria, and Uganda-and a global learning partner. Those considerations may include the need to generate insights on immunization timeliness and on catch-up activities, made particularly relevant in the post-pandemic context; the need to compare results across different age cohort years to better identify systematically missed communities and validate programmatic priorities, and also generate insights on changes under dynamic contexts such as the introduction of a new ZD intervention or for recovering from the impact of health system shocks. Some practical considerations such as the potential need for a larger sample size when including comparisons across multiple cohort years but a potential reduction in the need for household visits to find eligible children, an increase in recall bias when older age groups are included and a reduction in recall bias for the first year of life, and a potential reduction in sample size needs and time needed to detect impact when the first year of life is included. Finally, the inclusion of the first year of life cohort in the survey may be particularly relevant and improve the utility of evidence for decision-making and enable its use in rapid learning cycles, as insights will be generated for the population being currently targeted by the program. For some of those reasons, the ZDLH initiative decided to align on a recommendation to include the age cohort from 18 weeks to 23 months, with enough power to enable disaggregation of key results across the two different cohort years. We argue that flexibilities with the age cohort for inclusion in targeted surveys at the local level may be an important principle to be considered. More research is needed to better understand in which contexts improvements in timeliness of DTP1 in the first year of life will translate to improvements in ZD results in the age cohort of 12-23 months as defined by the global DTP1 indicator.

Measuring National Immunization System Performance: A Systematic Assessment of Available Resources.

BACKGROUND: Vaccination coverage is widely used to assess immunization performance but, on its own, provides insufficient information to drive improvements. Assessing the performance of underlying components of immunization systems is less clear, with several monitoring and evaluation (M&E) resources available for use in different operational settings and for different purposes. We studied these resources to understand how immunization system performance is measured. METHODS: We reviewed peer-reviewed and gray literature published since 2000 to identify M&E resources that include national-level indicators measuring the performance of immunization systems or their components (governance, financing, regulation, information systems, vaccine logistics, workforce, service delivery, and demand generation). We summarize indicators by the system components or outcomes measured and describe findings narratively. RESULTS: We identified 20 resources to monitor immunization program objectives and guide national strategic decision-making, encompassing 631 distinct indicators. Indicators for immunization program outcomes comprised the majority (124/631 [19.7%]), largely vaccination coverage (110/124 [88.7%]). Almost all resources (19/20 [95%]) included indicators for vaccine logistics (83/631 [13.2%]), and those for regulation (19/631 [3.0%]) and demand generation (28/631 [4.4%]) were least common. There was heterogeneity in how information systems (92/563 [14.6%]) and workforce (47/631 [7.4%]) were assessed across resources. Indicators for vaccination coverage in adults, data use in decision-making, equity and diversity, effectiveness of safety surveillance, and availability of a public health workforce were notably lacking. CONCLUSIONS: Between the resources identified in this review, we identified considerable variability and gaps in indicators assessing the performance of some immunization system components. Given the multitude of indicators, policymakers may be better served by tailoring evaluation resources to their specific context to gain useful insight into health system performance and improve data use in decision-making for immunization programs.

COVID-19 vaccine policy development in a sample of 44 countries - Key findings from a December 2021 survey of National Immunization Technical Advisory Groups (NITAGs).

National Immunization Technical Advisory Committees (NITAGs) are tasked with the responsibility of guiding ministries of health and national immunization programmes in their policy development processes. Many NITAGs rely on evidence reviewed by the World Health Organization's (WHO) Strategic Group of Experts(SAGE) on immunization and aim to adapt WHO's recommendations to their respective contexts. This relationship took on exceptional importance since the onset of the COVID-19 pandemic, during which NITAGs have expressed a notable struggle to craft appropriate policies on population prioritization and vaccine utilization in the face of supply constraints and complex programmatic and delivery logistics. This online survey was conducted to assess the usefulness of the SAGE guidance documents for COVID-19 vaccine policies and to examine the persisting needs and challenges facing NITAGs. Results confirmed that SAGE recommendations concerning COVID-19 vaccines are easy to access, understand, and adapt. They have been found to be comprehensive and timely under the data and time constrained circumstances confronting SAGE. The Global NITAG Network (GNN) appears to be the most popular vehicle for addressing questions among high income countries, in contrast to lower income countries who favour WHO Country or Regional Offices. NITAGs place much value on interaction with other NITAGs, which requires facilitation and could benefit from increased opportunities, especially within regions. It is further noted that some NITAGs have had to tackle issues during the pandemic not typically considered by SAGE, such as supply chain logistics and vaccine demand. Learning from the COVID-19 experience offers opportunities to strengthen NITAGs and the pandemic recovery effort through the development of more concrete procedures and consideration of more varied types of data, including implementation effectiveness and uptake data. There is also an opportunity for an increasing involvement of Country Office WHO personnel to support NITAGs, while ensuring information and evidence needs of countries are adequately reflected in SAGE deliberations.

Integration of other services with human papillomavirus vaccination; lessons from earlier in the life course highlight the need for new policy and implementation evidence.

Integration of vaccination against human papillomavirus (HPV) with other essential health services for adolescents has been proposed in global strategies and tested in demonstration projects in low- and middle-income countries (LMIC). Published experiences, global guidance, and one key example, the implementation of "HPV Plus" in Tanzania, all demonstrate the need for greater operational evidence to guide future implementation and policy. Review of experiences earlier in the life course, integrating post-partum family planning with infant immunization, show lessons from 13 LMICs that can apply to provision of adolescent health information and services alongside HPV vaccination. Three distinct models of integration emerge from this review comprising: 1) multiple tasks and functions by health staff providing vaccination and other care, or 2) secondary tasks added to the main function of vaccination, or 3) co-location of matched services provided by different staff. These models, with strengths and weaknesses demonstrated in family planning and immunization experiences, apply in different ways to the three main platforms used for HPV vaccination: school, facility or community. For HPV vaccination policy and programming, an initial need is to combine the existing evidence on vaccine service delivery - including coverage, efficiency, cost, and cost-effectiveness information - with what is known on how integration works in practice; the operational detail and models employed. This synthesis may enable assessment which models best suit the different service delivery platforms. An additional need is to link this with more tailored local assessments of the adolescent burden of disease and other determinants of their well-being to develop new thinking on what can and cannot be done to integrate other services alongside HPV vaccination. New approaches placing adolescents at the center are needed to design services tailored to their preferences and needs. The potential synergies with cervical cancer screening and treatment for older generations of women, also require further exploration. Coordinated action aligning HPV vaccination with broader adolescent health and wellbeing will generate social, economic and demographic benefits, which in themselves are sufficient justification to devote more attention to integrated approaches.

Evaluating the potential cost-effectiveness of microarray patches to expand access to hepatitis B birth dose vaccination in low-and middle-income countries: A modelling study.

Timely birth dose vaccination is key for achieving elimination of hepatitis B, however, programmatic requirements for delivering current vaccine presentations to births outside of health facilities inhibits coverage within many low-and middle-income countries (LMICs). Vaccine technologies in development such as microarray patches (MAPs) could assist in overcoming these barriers, but procurement could incur higher per-dose commodity costs than current ten-dose (US$0.34) and single-dose (US$0.62) vial presentations, necessitating an evaluation of the economic value proposition for MAPs. Within 80 LMICs offering universal hepatitis B birth dose vaccination, the cost-effectiveness of using MAPs to expand coverage was evaluated using a mathematical model. We considered three potential per dose MAP prices (US$1.65, US$3.30, and US$5.00), and two potential MAP use-cases: (1) MAPs are used by lay-health workers to expand birth dose coverage outside of health facility settings, and (2) MAPs are also preferred by qualified health workers, replacing a proportion of existing coverage from vaccine vials. Analysis took the health system perspective, was costed in 2020 US$, and discounted at 3% annually. Across minimal (1% additional coverage) and maximal (10% additional and 10% replacement coverage) MAP usage scenarios, between 2.5 (interquartile range [IQR]: 1.9, 3.1) and 38 (IQR: 28,44) thousand DALYs were averted over the estimated 2020 birth cohort lifetime in 80 LMICs. Efficiency of MAPs was greatest when used to provide additional coverage (scenario 1), on average saving US$88.65 ($15.44, $171.22) per DALY averted at a price of US$5.00 per MAP. Efficiency was reduced when used to replace existing coverage (scenario 2); however, at prices up to US$5.00 per MAP, we estimate this use-case could remain cost-effective in at least 73 (91%) modelled LMICs. Our findings suggest even at higher procurement costs, MAPs are likely to represent a highly cost-effective or cost-saving mechanism to expand reach of birth dose vaccination in LMICs.

Designing a Pro-Equity HPV Vaccine Delivery Program for Girls Who Have Dropped Out of School: Community Perspectives From Uttar Pradesh, India.

India experiences a substantial burden of cervical cancer and accounts for nearly one third of cervical cancer deaths worldwide. While human papillomavirus (HPV) vaccines have been introduced subnationally in some states, HPV has not yet been rolled out nationally. Given the target age group, schools are the most common delivery channel for HPV vaccines, but this fails to account for local girls who never attended or no longer attend school. We conducted a qualitative, design-informed, community-based study conducted in Uttar Pradesh, India. We assessed facilitators and barriers among out-of-school girls and proposed program characteristics to inform the design of pro-equity HPV vaccine delivery programs for out-of-school girls. Programs should improve parental knowledge of the risk of cervical cancer, engage vaccinated girls as vaccine champions, utilize varied media options for low-literacy populations, and ensure that HPV vaccine services are accessible and flexible to accommodate out-of-school girls. In areas with poor or irregular school attendance among adolescent girls, HPV vaccine coverage will remain suboptimal until programs can effectively address their needs and reach this priority population. Our findings present a meaningful opportunity for program planners to purposefully design HPV vaccination programs according to these parameters, rather than modifying existing programs to include HPV vaccine. Adolescent girls, their parents, and other community members should be involved in program design to ensure that the program can effectively meet the needs of adolescent girls who are not in school.

Point-of-care testing and treatment of sexually transmitted and genital infections during pregnancy in Papua New Guinea (WANTAIM trial): protocol for an economic evaluation alongside a cluster-randomised trial.

INTRODUCTION: Left untreated, sexually transmitted and genital infections (henceforth STIs) in pregnancy can lead to serious adverse outcomes for mother and child. Papua New Guinea (PNG) has among the highest prevalence of curable STIs including syphilis, chlamydia, gonorrhoea, trichomoniasis and bacterial vaginosis, and high neonatal mortality rates. Diagnosis and treatment of these STIs in PNG rely on syndromic management. Advances in STI diagnostics through point-of-care (PoC) testing using GeneXpert technology hold promise for resource-constrained countries such as PNG. This paper describes the planned economic evaluation of a cluster-randomised cross-over trial comparing antenatal PoC testing and immediate treatment of curable STIs with standard antenatal care in two provinces in PNG. METHODS AND ANALYSIS: Cost-effectiveness of the PoC intervention compared with standard antenatal care will be assessed prospectively over the trial period (2017-2021) from societal and provider perspectives. Incremental cost-effectiveness ratios will be calculated for the primary health outcome, a composite measure of the proportion of either preterm birth and/or low birth weight; for life years saved; for disability-adjusted life years averted; and for non-health benefits (financial risk protection and improved health equity). Scenario analyses will be conducted to identify scale-up options, and budget impact analysis will be undertaken to understand short-term financial impacts of intervention adoption on the national budget. Deterministic and probabilistic sensitivity analysis will be conducted to account for uncertainty in key model inputs. ETHICS AND DISSEMINATION: This study has ethical approval from the Institutional Review Board of the PNG Institute of Medical Research; the Medical Research Advisory Committee of the PNG National Department of Health; the Human Research Ethics Committee of the University of New South Wales; and the Research Ethics Committee of the London School of Hygiene and Tropical Medicine. Findings will be disseminated through national stakeholder meetings, conferences, peer-reviewed publications and policy briefs. TRIAL REGISTRATION NUMBER: ISRCTN37134032.

Characterization and Associated Costs of Constipation Relating to Exposure to Strong Opioids in England: An Observational Study.

PURPOSE: Opioid use is associated with gastrointestinal adverse events, including nausea and constipation. We used a real-world dataset to characterize the health care burden associated with opioid-induced constipation (OIC) with particular emphasis on strong opioids. METHODS: This retrospective cohort study was conducted using the Clinical Practice Research Datalink, a large UK primary care dataset linked to hospital data. Patients prescribed opioids during 2016 were selected and episodes of opioid therapy constructed. Episodes with ≥84 days of exposure were classified as chronic, with date of first prescription as the index date. The main analysis focused on patients prescribed strong opioids who were laxative naive. Constipation was defined by ≥2 laxative prescriptions during the opioid episode. Patients for whom initial laxative therapy escalated by switch, augmentation, or dose were defined as OIC unstable, and the first 3 lines of OIC escalation were classified. Health care costs accrued in the first 12 months of the opioid episode were aggregated and compared. FINDINGS: A total of 27,629 opioid episodes were identified; 5916 (21.4%) involved a strong opioid for patients who were previously laxative naive. Of these patients, 2886 (48.8%) were defined as the OIC population; 941 (33.26%) were classified as stable. Of the 1945 (67.4%) episodes classified as unstable, 849 (43.7%), 360 (18.5%), and 736 (37.8%) had 1, 2, and ≥3 changes of laxative prescription, respectively. Patients without OIC had lower costs per patient year (£3822 [US$5160/€4242]) compared with OIC (£4786 [US$6461/€5312]). Costs increased as patients had multiple changes in therapy: £4696 (US$6340/€5213), £4749 (US$6411/€5271), and £4981 (US$6724/€5529) for 1, 2, and ≥3 changes, respectively. The adjusted cost ratio relative to non-OIC was 1.14 (95% CI, 1.09-1.32) for those classified as stable and 1.19 (95% CI, 1.09-1.32) for those with ≥3 laxative changes. Similar patterns were observed for patients taking anyopioid, with costs increased for those classified as having OIC (£3727 [US$5031/€4137] vs £2379 [US$3212 /€2641),and for those patients classified as unstable versus stable (£3931 [US$5307/€4363] vs £3432 [US$4633/€3810). Costs increased with each additional line of therapy from £3701 (US$4996/€4108), £3916 (US$5287/€4347), and £4318 (US$5829/€4793). IMPLICATIONS: OIC was a common adverse event of opioid treatment and was poorly controlled for a large number of patients. Poor control was associated with increased health care costs. The impact of OIC should be considered when prescribing opioids. These results should be interpreted with consideration of the caveats associated with the analysis of routine data.

Men's and women's knowledge of danger signs relevant to postnatal and neonatal care-seeking: A cross sectional study from Bungoma County, Kenya.

BACKGROUND: Neonatal and maternal mortality rates remain high in Kenya. Knowledge of neonatal danger signs may reduce delay in deciding to seek care. Evidence is emerging on the influential role of male partners in improving maternal and newborn health. This study analysed the factors that determine men's and women's knowledge and practices in postnatal and neonatal care-seeking, in order to inform design of future interventions. METHODS: A quantitative, cross-sectional study was undertaken in Bungoma County, Kenya. Women who had recently given birth (n = 348) and men whose wives had recently given birth (n = 82) completed questionnaires on knowledge and care-seeking practices relating to the postnatal period. Univariate and multivariate logistic regression analyses were performed to investigate associations with key maternal and newborn health outcomes. RESULTS: 51.2% of women and 50.0% of men knew at least one neonatal danger sign, however women knew more individual danger signs than men. In the univariate model, women's knowledge of a least one neonatal danger sign was associated with attending antenatal care ≥4 times (OR 4.46, 95%CI 2.73-7.29, p<0.001), facility birth (OR 3.26, 95%CI 1.89-5.72, p<0.001), and having a male partner accompany them to antenatal care (OR 3.34, 95%CI 1.35-8.27, p = 0.009). Higher monthly household income (≥10,000KSh, approximately US$100) was associated with facility delivery (AOR 11.99, 95%CI 1.59-90.40, p = 0.009). CONCLUSION: Knowledge of neonatal danger signs was low, however there was an association between knowledge of danger signs and increased healthcare service use, including male partner involvement in antenatal care. Future interventions should consider the extra costs of facility delivery and the barriers to men participating in antenatal and postnatal care.

Ending malnutrition in all its forms requires scaling up proven nutrition interventions and much more: a 129-country analysis.

BACKGROUND: Sustainable Development Goal (SDG) 2.2 calls for an end to all forms of malnutrition, with 2025 targets of a 40% reduction in stunting (relative to 2012), for wasting to occur in less than 5% of children, and for a 50% reduction in anaemia in women (15-49 years). We assessed the likelihood of countries reaching these targets by scaling up proven interventions and identified priority interventions, based on cost-effectiveness. METHODS: For 129 countries, the Optima Nutrition model was used to compare 2019-2030 nutrition outcomes between a status quo (maintained intervention coverage) scenario and a scenario where outcome-specific interventions were scaled up to 95% coverage over 5 years. The average cost-effectiveness of each intervention was calculated as it was added to an expanding package of interventions. RESULTS: Of the 129 countries modelled, 46 (36%), 66 (51%) and 0 (0%) were on track to achieve the stunting, wasting and anaemia targets respectively. Scaling up 18 nutrition interventions increased the number of countries reaching the SDG 2.2 targets to 50 (39%), 83 (64%) and 7 (5%) respectively. Intermittent preventative treatment of malaria during pregnancy (IPTp), infant and young child feeding education, vitamin A supplementation and lipid-based nutrition supplements for children produced 88% of the total impact on stunting, with average costs per case averted of US$103, US$267, US$556 and US$1795 when interventions were consecutively scaled up, respectively. Vitamin A supplementation and cash transfers produced 100% of the total global impact on prevention of wasting, with average costs per case averted of US$1989 and US$19,427, respectively. IPTp, iron and folic acid supplementation for non-pregnant women, and multiple micronutrient supplementation for pregnant women produced 85% of the total impact on anaemia prevalence, with average costs per case averted of US$9, US$35 and US$47, respectively. CONCLUSIONS: Prioritising nutrition investment to the most cost-effective interventions within the country context can maximise the impact of funding. A greater focus on complementing nutrition-specific interventions with nutrition-sensitive ones that address the social determinants of health is critical to reach the SDG targets.

Healthcare utilization and associated costs following initiation of perampanel in patients with epilepsy.

PURPOSE: We compared health service utilization and costs for patients with epilepsy before and after initiation of perampanel and compared with matched controls. METHOD: Patients were selected from the Clinical Practice Research Datalink (CPRD). Patients initiating perampanel were matched to controls initiating an alternate add-on therapy for the same underlying epilepsy subtype. First prescription defined index date. Primary and secondary care contacts and associated costs were aggregated in the 12 months before and after index date. Secondary care contacts were available for a subset (~60%) of patients. RESULTS: Three hundred and forty-three patients treated with perampanel were identified. One hundred and eighty-three (53.4%) were male, mean age was 39.1 (sd: 16.0). Mean epilepsy duration was 21.1 (standard deviation (sd): 13.3) years. Two hundred and eighty-seven (83.7%) were matched to controls. Inpatient admissions with a primary diagnosis of epilepsy (0.5 versus 0.2 per patient-year (ppy), p = 0.002) and neurology specific outpatient appointments (3.2 versus 2.9 ppy, p = 0.041) were significantly reduced following initiation with perampanel. Total costs attributable to epilepsy (£1889 to 1477 ppy) and overall secondary costs (£2593 to £2102) were also significantly reduced. There was no significant difference in primary care, outpatient, or general inpatient admissions. Compared with controls, there was a significant reduction in primary epilepsy admissions (incidence rate ratio (IRR): 0.423; 95% Confidence intervals (CI): 0.198-0.835) but a significant increase in outpatient appointments (1.306; 95% CI: 1.154-1.478) and accident and emergency contacts (1.603; 95% CI: 1.081-2.390) for patients treated with perampanel. CONCLUSION: Treatment with perampanel is associated with reduced epilepsy-related inpatient admissions and accident and emergency contacts.

Use of controlled temperature chain and compact prefilled auto-disable devices to reach 2030 hepatitis B birth dose vaccination targets in LMICs: a modelling and cost-optimisation study.

BACKGROUND: Hepatitis B causes more than 800 000 deaths globally each year. Perinatal infections are a major driver of this burden but can be prevented by vaccination within 24 h of birth. Currently, only 44% of newborn babies in low-income and middle-income countries (LMICs) receive a timely birth dose. We investigated the effects and cost-effectiveness of implementing ambient storage of hepatitis B vaccines under a controlled temperature chain (CTC) protocol and the use of compact prefilled auto-disable (CPAD) devices for community births. METHODS: In this mathematical modelling study of perinatal hepatitis B transmission and disease progression, we estimated the coverage impact and cost-effectiveness of implementing CTC and CPAD interventions in the six Global Burden of Disease (GBD) regions containing LMICs. Combinations of four different scenarios of birth dose delivery strategies (cold chain, CTC) and interventions (needle and syringe, CPAD) were modelled across facility or community birth locations. We also estimated the minimum cost and most cost-effective strategy to achieve the WHO 90% hepatitis B birth dose coverage target in GBD regions and in 46 LMICs with a reported coverage of less than 90%. FINDINGS: Current delivery protocols achieved a maximum coverage of 65% (IQR 64-65) across GBD regions. Reaching 90% hepatitis B birth dose coverage across all GBD regions was estimated to cost a minimum of US$687·5 million per annum ($494·0 million more than the estimated current expenditure), of which $516·5 million (75%) was required for CTC and CPAD interventions. Reaching 90% coverage in this way was estimated to be cost saving in five of the six regions (and in 40 of 46 LMICs individually assessed) due to the disease costs averted, with the cost per disability-adjusted life-years averted being less than $83·27 otherwise. INTERPRETATION: Hepatitis B birth dose coverage of 90% is unlikely to be reached under current protocols. CTC and CPAD vaccine strategies present cost-effective solutions to overcome coverage barriers. FUNDING: The Burnet Institute.

Strengthening routine immunization in Papua New Guinea: a cross-sectional provincial assessment of front-line services.

BACKGROUND: Routine immunization programs face many challenges in settings such as Papua New Guinea with dispersed rural populations, rugged geography and limited resources for transport and health. Low routine coverage contributes to disease outbreaks such as measles and the polio that re-appeared in 2018. We report on an in-depth local assessment that aimed to document immunization service provision so as to review a new national strategy, and consider how routine immunization could be better strengthened. METHODS: In East New Britain Province, over 2016 and 17, we carried out a cross-sectional assessment of 12 rural health facilities, staff and clients. The study was timed to follow implementation of a new national strategy for strengthening routine immunization. We used interview, structured observation, and records review, informed by theory-based evaluation, a World Health Organization quality checklist, and other health services research tools. RESULTS: We documented strengths and weaknesses across six categories of program performance relevant to national immunization strategy and global standards. We found an immunization service with an operational level of staff, equipment and procedures in place; but one that could reach only half to two thirds of its target population. Stronger routine services require improvement in: understanding of population catchments, tracking the unvaccinated, reach and efficiency of outreach visits, staff knowledge of vaccination at birth and beyond the first year of life, handling of multi-dose vials, and engagement of community members. Many local suggestions to enhance national plans, included more reliable on-demand services, integration of other family health services and increased involvement of men. CONCLUSIONS: The national strategy addresses most local gaps, but implementation and resourcing requires greater commitment. Long-term strengthening requires a major increase in centrally-allocated resources, however there are immediate locally feasible steps within current resources that could boost coverage and quality of routine immunization especially through better population-based local planning, and stronger community engagement. Our results also suggest areas where vaccination campaigns in PNG can contribute to routine immunization services.

Cost-effectiveness of the controlled temperature chain for the hepatitis B virus birth dose vaccine in various global settings: a modelling study.

BACKGROUND: The controlled temperature chain (CTC) strategy allows vaccines to be kept outside the cold chain for a short period of time. In remote rural areas, the CTC strategy for the hepatitis B virus (HBV) birth dose vaccination could improve its geographical coverage and timeliness of delivery, but with additional outreach costs. We assessed the cost-effectiveness of the CTC strategy for the HBV birth dose across six world regions and 72 countries according to their HBV prevalence, delivery costs, and birth dose coverage and timing. METHODS: By use of a mathematical model of perinatal HBV transmission and disease progression, we calculated per 1000 births the total HBV-related disability-adjusted life-years (DALYs) and costs, including vaccine delivery costs and costs associated with HBV-related disease, with and without the CTC strategy. FINDINGS: A CTC strategy produced health benefits in all regions and was cost-saving in the regions of east Asia and Pacific, Latin America and Caribbean, sub-Saharan Africa, and north Africa and Middle East. The CTC strategy cost US$0·15 (IQR -7·11 to 4·75) per DALY averted in the central and eastern Europe and central Asia region and $79·72 (66·47 to 94·47) in the south Asia region. Within individual countries, more savings were achieved and more DALYs averted in areas with above average HBV prevalence, below average birth dose coverage, or later than average birth dose delivery. INTERPRETATION: A CTC outreach strategy that improves the timing and coverage of the HBV birth dose vaccination is likely to be cost-saving and reduce the burden of HBV infection associated with perinatal transmission. FUNDING: Burnet Institute.

Poor compliance and increased mortality, depression and healthcare costs in patients with congenital adrenal hyperplasia.

OBJECTIVES: To evaluate the risks of depression and all-cause mortality, healthcare utilisation costs and treatment adherence in congenital adrenal hyperplasia (CAH) in the United Kingdom. DESIGN AND METHODS: A retrospective, matched-cohort study using UK primary-care data from the Clinical Practice Research Datalink linked to hospital and death certification data. Patients diagnosed with CAH and having ≥1 corticosteroid prescription were matched 1:10 to reference subjects. Risk of death and lifetime prevalence of depression were compared using Cox regression models. Direct financial costs were estimated for healthcare contacts. Treatment adherence was measured by medical possession ratio (MPR). RESULTS: 605 patients with CAH were identified; 562 were matched. 270 CAH patients (2700 controls) were linkable to death-certificate data, with adjusted hazard ratio for all-cause mortality 5.17 (95% CI 2.81-9.50). Mean (s.d.) age at death in CAH patients was 54.8 (23.9) vs 72.8 (18.0) years in control patients. The prevalence ratio of depression in CAH vs control patients was 1.28 (95% CI 1.13-1.45). Mean (s.d.) annual healthcare costs were higher in CAH than controls: at age 0-6 years, £7038 (£14 846) vs £2879 (£13 972, P < 0.001); 7-17 years, £3766 (£7494) vs £1232 (£2451, P < 0.001); 18-40 years, £1539 (£872) vs £1344 (£1620, P = 0.007) and ≥41 years, £4204 (£4863) vs £1651 (£2303, P < 0.001). Treatment adherence was lowest in adults, with 141 (36%) of 396 eligible patients having an MPR <80%. CONCLUSIONS: This first analysis of CAH in routine UK healthcare suggests that patients with CAH have increased mortality, depression and healthcare utilisation and low treatment adherence.

Healthcare resource utilization and related financial costs associated with glucose lowering with either exenatide or basal insulin: A retrospective cohort study.

AIMS: Type 2 diabetes is a major health problem placing increasing demands on healthcare systems. Our objective was to estimate healthcare resource use and related financial costs following treatment with exenatide-based regimens prescribed as once-weekly (EQW) or twice-daily (EBID) formulations, compared with regimens based on basal insulin (BI). MATERIALS AND METHODS: This retrospective cohort study used data from the UK Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics (HES). Patients with type 2 diabetes who received exenatide or BI between 2009 and 2014 as their first recorded exposure to injectable therapy were selected. Costs were attributed to primary care contacts, diabetes-related prescriptions and inpatient admissions using standard UK healthcare costing methods (2014 prices). Frequency and costs were compared between cohorts before and after matching by propensity score using Poisson regression. RESULTS: Groups of 8723, 218 and 2180 patients receiving BI, EQW and EBID, respectively, were identified; 188 and 1486 patients receiving EQW and EBID, respectively, were matched 1:1 to patients receiving BI by propensity score. Among unmatched cohorts, total crude mean costs per patient-year were £2765 for EQW, £2549 for EBID and £4080 for BI. Compared with BI, the adjusted annual cost ratio (aACR) was 0.92 (95% CI, 0.91-0.92) for EQW and 0.82 (95% CI, 0.82-0.82) for EBID. Corresponding costs for the propensity-matched subgroups were £2646 vs £3283 (aACR, 0.80, 0.80-0.81) for EQW vs BI and £2532 vs £3070 (aACR, 0.84, 0.84-0.84) for EBID vs BI. CONCLUSION: Overall, exenatide once-weekly and twice-daily-based regimens were associated with reduced healthcare resource use and costs compared with basal-insulin-based regimens.

Correlates of male involvement in maternal and newborn health: a cross-sectional study of men in a peri-urban region of Myanmar.

BACKGROUND: Evidence suggests that increasing male involvement in maternal and newborn health (MNH) may improve MNH outcomes. However, male involvement is difficult to measure, and further research is necessary to understand the barriers and enablers for men to engage in MNH, and to define target groups for interventions. Using data from a peri-urban township in Myanmar, this study aimed to construct appropriate indicators of male involvement in MNH, and assess sociodemographic, knowledge and attitude correlates of involvement. METHODS: A cross-sectional study of married men with one or more children aged up to one year was conducted in 2012. Structured questionnaires measured participants' involvement in MNH, and their sociodemographic characteristics, knowledge and attitudes. An ordinal measure of male involvement was constructed describing the subject's participation across five areas of MNH, giving a score of 1-4. Proportional-odds regression models were developed to determine correlates of male involvement. RESULTS: A total of 210 men participated in the survey, of which 203 provided complete data. Most men reported involvement level scores of either 2 or 3 (64 %), with 13 % reporting the highest level (score of 4). Involvement in MNH was positively associated with wives' level of education (AOR = 3.4; 95 % CI: 1.9-6.2; p < 0.001) and men's level of knowledge of MNH (AOR = 1.2; 95 % CI: 1.1-1.3; p < 0.001), and negatively correlated with number of children (AOR = 0.78; 95 % CI: 0.63-0.95; p = 0.016). CONCLUSIONS: These findings can inform the design of programs aiming to increase male involvement, for example by targeting less educated couples and addressing their knowledge of MNH. The composite index proved a useful summary measure of involvement; however, it may have masked differential determinants of the summed indicators. There is a need for greater understanding of the influence of gender attitudes on male involvement in Myanmar and more robust indicators that capture these gender dynamics for use both in Myanmar and globally.

The prevalence and incidence, resource use and financial costs of treating people with attention deficit/hyperactivity disorder (ADHD) in the United Kingdom (1998 to 2010).

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is a common disorder that often presents in childhood and is associated with increased healthcare resource use. The aims of this study were to characterise the epidemiology of diagnosed ADHD in the UK and determine the resource use and financial costs of care. METHODS: For this retrospective, observational cohort study, patients newly diagnosed with ADHD between 1998 and 2010 were identified from the UK Clinical Practice Research Datalink (CPRD) and matched to a randomly drawn control group without a diagnosis of ADHD. The prevalence and incidence of diagnosed ADHD were calculated. Resource utilisation and corresponding financial costs post-diagnosis were estimated for general practice contacts, investigations, prescriptions, outpatient appointments, and inpatient admissions. RESULTS: Incidence of diagnosed ADHD (and percentage change using 1998 as a reference) increased from 6.9 per 100,000 population in 1998 to 12.2 per 100,000 (78%) in 2007 and then fell to 9.9 per 100,000 (44%) by 2009. The corresponding prevalence figures were 30.5, 88.9 (192%) and 81.5 (167%) per 100,000. Incidence and prevalence were higher in males than females. Mean annual total healthcare costs were higher for ADHD cases than controls (£1,327 versus £328 for year 1, £1,196 vs. £337 for year 2, £1,148 vs. £316 for year 3, £1,126 vs. £325 for year 4, and £1,112 vs. £361 for year 5). CONCLUSIONS: The prevalence of diagnosed ADHD in routine practice in the UK was notably lower than in previous reports, and both prevalence and incidence of diagnosed ADHD in primary care have fallen since 2007. Financial costs were more than four times higher in those with ADHD than in those without ADHD.

Evaluation of the incremental cost to the National Health Service of prescribing analogue insulin.

Introduction Insulin analogues have become increasingly popular despite their greater cost compared with human insulin. The aim of this study was to calculate the incremental cost to the National Health Service (NHS) of prescribing analogue insulin preparations instead of their human insulin alternatives. Methods Open-source data from the four UK prescription pricing agencies from 2000 to 2009 were analysed. Cost was adjusted for inflation and reported in UK pounds at 2010 prices. Results Over the 10-year period, the NHS spent a total of £2732 million on insulin. The total annual cost increased from £156 million to £359 million, an increase of 130%. The annual cost of analogue insulin increased from £18.2 million (12% of total insulin cost) to £305 million (85% of total insulin cost), whereas the cost of human insulin decreased from £131 million (84% of total insulin cost) to £51 million (14% of total insulin cost). If it is assumed that all patients using insulin analogues could have received human insulin instead, the overall incremental cost of analogue insulin was £625 million. Conclusion Given the high marginal cost of analogue insulin, adherence to prescribing guidelines recommending the preferential use of human insulin would have resulted in considerable financial savings over the period.

The relationship between self-reported severe pain and measures of socio-economic disadvantage.

AIMS: To determine the association of severe pain with socioeconomic characteristics. METHODS: Data was extracted from the Health Survey for England (HSE), 2005. The HSE is a series of annual cross-sectional surveys designed to describe the health of people living in private homes in England, from a random sample of 720 postcode sectors. Interviewees were ≥ 16 years. Pain severity was characterised by the EQ-5D. Socioeconomic status was classified by ability to work, social security benefits, the National Statistics Socio-economic Classification (NS-SEC) and the Index of Multiple Deprivation (IMD). RESULTS: Pain status was recorded for 9419 subjects of whom 431 (4.6%) reported severe pain. 156 of those reporting severe pain were of working age. Of these 68 (43.6%) stated they were unable to work due to sickness or disability and 64 (41.0%) claimed a state benefit. After adjusting for disease and demographic variables, severe pain was associated with the IMD with an odds ratio of 1.65 (95% CI 1.16-2.34, p=0.005), NS-SEC (OR=2.94; 95% CI 1.76-4.91) and equivalised household income (lowest versus highest quintile; OR=2.58 (95% CI 1.46-4.57, p=0.001). CONCLUSIONS: This study demonstrated significant associations between pain and socio-economic disadvantage. Apart from the direct impact upon the individual, this clearly has wider societal implications in terms of additional health and social care costs for affected people.