A review of moxidectin vs. other macrocyclic lactones for prevention of heartworm disease in dogs with an appraisal of two commercial formulations.

Macrocyclic lactones (MLs) are the only drug class currently licensed for heartworm disease prophylaxis. Macrocyclic lactones kill third- and fourth-stage larvae of Dirofilaria immitis, thus preventing the development of adult worms in dogs, which are responsible for heartworm disease, a potentially life-threatening condition. Despite considerable overlap in terms of endectocide spectrum, several important differences distinguish moxidectin from other MLs. Moxidectin has beneficial pharmacokinetic characteristics, such as a longer half-life and greater tissue distribution compared to ivermectin. Additionally, moxidectin has a greater margin of safety compared to ivermectin in dogs with ABCB1 (previously MDR1) gene-defect, which is commonly recognized in collies and other breeds. Multiple laboratory studies have shown that moxidectin is more effective than other commonly used heartworm preventives against resistant strains of D. immitis. This improved efficacy benefits individual dogs and helps reduce the risk of spreading resistant strains within the community. Despite the presence of proven resistant strains in the United States, non-compliance with preventive measures remains a major factor contributing to the diagnosis of heartworm disease in dogs. In retrospective analyses, the oral moxidectin combination product Simparica Trio® (sarolaner, moxidectin, and pyrantel) was associated with increased compliance, resulting in more time of protection compared to dogs receiving flea/tick and heartworm preventive products separately. Compliance with the extended-release moxidectin injectables ProHeart® 6 and ProHeart® 12 was higher than with monthly heartworm preventives, as they provide 6 months or a full year of protection with one single injection, respectively, and revenues remain in the veterinary clinics as injectable moxidectin cannot be sourced through online retailers.

High-resolution mapping of essential maternal and child health service coverage in Nigeria: a machine learning approach.

BACKGROUND: National-level coverage estimates of maternal and child health (MCH) services mask district-level and community-level geographical inequities. The purpose of this study is to estimate grid-level coverage of essential MCH services in Nigeria using machine learning techniques. METHODS: Essential MCH services in this study included antenatal care, facility-based delivery, childhood vaccinations and treatments of childhood illnesses. We estimated generalised additive models (GAMs) and gradient boosting regressions (GB) for each essential MCH service using data from five national representative cross-sectional surveys in Nigeria from 2003 to 2018 and geospatial socioeconomic, environmental and physical characteristics. Using the best-performed model for each service, we map predicted coverage at 1 km2 and 5 km2 spatial resolutions in urban and rural areas, respectively. RESULTS: GAMs consistently outperformed GB models across a range of essential MCH services, demonstrating low systematic prediction errors. High-resolution maps revealed stark geographic disparities in MCH service coverage, especially between rural and urban areas and among different states and service types. Temporal trends indicated an overall increase in MCH service coverage from 2003 to 2018, although with variations by service type and location. Priority areas with lower coverage of both maternal and vaccination services were identified, mostly located in the northern parts of Nigeria. CONCLUSION: High-resolution spatial estimates can guide geographic prioritisation and help develop better strategies for implementation plans, allowing limited resources to be targeted to areas with lower coverage of essential MCH services.

Retrospective analyses of heartworm (Dirofilaria immitis) disease and ectoparasite preventive medication compliance in veterinary practices in the USA.

BACKGROUND: Compliance failure with administration of heartworm (HW) disease preventives has been reported as the main contributor to HW disease incidence in medicalized dogs. This study aimed to evaluate purchase compliance with different canine HW preventive products in the USA. METHODS: Anonymized transaction data from clinics throughout the USA served as the basis for two retrospective analyses. We first examined the monthly equivalent doses of HW preventive purchases from clinics that had implemented extended-release moxidectin injectables ProHeart® 6 (PH6) and/or ProHeart® 12 (PH12) compared to clinics that prescribed monthly HW preventatives (MHWP) only. In the second analysis, the purchase compliance in practices that dispensed only flea and tick (FT) and HW products separately but did not dispense combination products (dual-therapy practices) was compared to the purchase compliance with the combination product Simparica Trio® (sarolaner, moxidectin, and pyrantel chewable tablets), purchased in clinics having implemented combination therapy in their formulary (combination-therapy practices). In both analyses, the numbers of monthly doses dispensed annually per dog were calculated. RESULTS: Transaction data from 3,539,990 dogs in 4615 practices were included in the first analysis. In dogs administered PH12 or PH6, the numbers of monthly equivalent doses were 12 and 8.1, respectively. In both clinic types, the average annual number of MHWP doses totaled 7.3. In the second analysis, a total of 919 practices were identified as combination-therapy practices and 434 as dual-therapy-only practices. A total of 246,654 dogs (160,854 dogs in dual-therapy practices and 85,800 dogs in combination-therapy practices) were included in the calculation of the average annual number of monthly doses, which totaled 6.8 (HW preventive products) and 4.4 (FT products) in dual-therapy practices compared to 7.2 months for both FT and HW preventives with Simparica Trio® across both practice types. CONCLUSIONS: The injectable HW preventive PH12 is the only product that provides 12 months of heartworm disease prevention in a single veterinarian-administered injection. When choosing a monthly preventive, the combination therapy was associated with a greater purchase compliance compared with FT and HW products being dispensed separately.

Assessing COVID-19 pandemic policies and behaviours and their economic and educational trade-offs across US states from Jan 1, 2020, to July 31, 2022: an observational analysis.

BACKGROUND: The USA struggled in responding to the COVID-19 pandemic, but not all states struggled equally. Identifying the factors associated with cross-state variation in infection and mortality rates could help to improve responses to this and future pandemics. We sought to answer five key policy-relevant questions regarding the following: 1) what roles social, economic, and racial inequities had in interstate variation in COVID-19 outcomes; 2) whether states with greater health-care and public health capacity had better outcomes; 3) how politics influenced the results; 4) whether states that imposed more policy mandates and sustained them longer had better outcomes; and 5) whether there were trade-offs between a state having fewer cumulative SARS-CoV-2 infections and total COVID-19 deaths and its economic and educational outcomes. METHODS: Data disaggregated by US state were extracted from public databases, including COVID-19 infection and mortality estimates from the Institute for Health Metrics and Evaluation's (IHME) COVID-19 database; Bureau of Economic Analysis data on state gross domestic product (GDP); Federal Reserve economic data on employment rates; National Center for Education Statistics data on student standardised test scores; and US Census Bureau data on race and ethnicity by state. We standardised infection rates for population density and death rates for age and the prevalence of major comorbidities to facilitate comparison of states' successes in mitigating the effects of COVID-19. We regressed these health outcomes on prepandemic state characteristics (such as educational attainment and health spending per capita), policies adopted by states during the pandemic (such as mask mandates and business closures), and population-level behavioural responses (such as vaccine coverage and mobility). We explored potential mechanisms connecting state-level factors to individual-level behaviours using linear regression. We quantified reductions in state GDP, employment, and student test scores during the pandemic to identify policy and behavioural responses associated with these outcomes and to assess trade-offs between these outcomes and COVID-19 outcomes. Significance was defined as p<0·05. FINDINGS: Standardised cumulative COVID-19 death rates for the period from Jan 1, 2020, to July 31, 2022 varied across the USA (national rate 372 deaths per 100 000 population [95% uncertainty interval [UI] 364-379]), with the lowest standardised rates in Hawaii (147 deaths per 100 000 [127-196]) and New Hampshire (215 per 100 000 [183-271]) and the highest in Arizona (581 per 100 000 [509-672]) and Washington, DC (526 per 100 000 [425-631]). A lower poverty rate, higher mean number of years of education, and a greater proportion of people expressing interpersonal trust were statistically associated with lower infection and death rates, and states where larger percentages of the population identify as Black (non-Hispanic) or Hispanic were associated with higher cumulative death rates. Access to quality health care (measured by the IHME's Healthcare Access and Quality Index) was associated with fewer total COVID-19 deaths and SARS-CoV-2 infections, but higher public health spending and more public health personnel per capita were not, at the state level. The political affiliation of the state governor was not associated with lower SARS-CoV-2 infection or COVID-19 death rates, but worse COVID-19 outcomes were associated with the proportion of a state's voters who voted for the 2020 Republican presidential candidate. State governments' uses of protective mandates were associated with lower infection rates, as were mask use, lower mobility, and higher vaccination rate, while vaccination rates were associated with lower death rates. State GDP and student reading test scores were not associated with state COVD-19 policy responses, infection rates, or death rates. Employment, however, had a statistically significant relationship with restaurant closures and greater infections and deaths: on average, 1574 (95% UI 884-7107) additional infections per 10 000 population were associated in states with a one percentage point increase in employment rate. Several policy mandates and protective behaviours were associated with lower fourth-grade mathematics test scores, but our study results did not find a link to state-level estimates of school closures. INTERPRETATION: COVID-19 magnified the polarisation and persistent social, economic, and racial inequities that already existed across US society, but the next pandemic threat need not do the same. US states that mitigated those structural inequalities, deployed science-based interventions such as vaccination and targeted vaccine mandates, and promoted their adoption across society were able to match the best-performing nations in minimising COVID-19 death rates. These findings could contribute to the design and targeting of clinical and policy interventions to facilitate better health outcomes in future crises. FUNDING: Bill & Melinda Gates Foundation, J Stanton, T Gillespie, J and E Nordstrom, and Bloomberg Philanthropies.

Prevention and long-term outcomes of naturally occurring canine heartworm infection in primary care settings.

Background: This study had two objectives: first, to examine the association between the history of heartworm preventive purchase compliance and the risk of positive heartworm tests, and second to preliminarily investigate the long-term cardiac outcomes of heartworm disease in dogs that had undergone successful adulticidal therapy. Methods: A retrospective cohort study design was used for both analyses, using anonymous transaction data from Covetrus (retrospective analysis 1) and anonymized medical records from Banfield Pet Hospital (retrospective analysis 2), both including canine patients across the USA. The first analysis examined the relative risk (RR) of a positive heartworm test in dogs with lapses in heartworm preventive purchase history compared to dogs that had no history of a preventive purchase six to 24 months prior to the test. In the second analysis, a long-term evaluation of structured diagnostic codes pertaining to cardiac diseases and risk assessment of outcomes was performed in dogs that had previously been successfully treated for heartworm disease compared to dogs that never had a positive heartworm test. Results: 83,478 unique patients were included in the first analysis. Compared to 32,413 dogs with no history of a heartworm preventive purchase, 44,410 dogs with lapses in monthly preventive purchases had a reduced risk of testing positive for heartworm disease (RR = 0.36, p < 0.0001). Dogs (n = 6,655) with lapses in injectable heartworm preventive administration had a decreased risk of a positive test versus dogs with no preventive purchases (RR = 0.15, p < 0.0001), as well as versus dogs with lapses in monthly heartworm preventive purchases (RR = 0.28, p = 0.0024). In the second analysis, 6,138 patients treated for heartworm infection were found to have significantly (p < 0.001) elevated risks of right heart failure (RR = 3.59), left heart failure (RR = 1.83), or cardiomyopathy (RR = 2.79) compared to 4,022,752 patients that never had a positive heartworm test. Conclusion: This study highlights the importance of compliance with heartworm preventive guidelines, to reduce the risk of heartworm disease in dogs, which is not only a potentially life-threatening condition in the short-term but also associated with long-term negative cardiac outcomes.

Factors consistently associated with utilisation of essential maternal and child health services in Nigeria: analysis of the five Nigerian national household surveys (2003-2018).

OBJECTIVE: This study aims to identify the individual and contextual factors consistently associated with utilisation of essential maternal and child health services in Nigeria across time and household geolocation. DESIGN, SETTING AND PARTICIPANTS: Secondary data from five nationally representative household surveys conducted in Nigeria from 2003 to 2018 were used in this study. The study participants are women and children depending on essential maternal and child health (MCH) services. OUTCOME MEASURES: The outcome measures were indicators of whether participants used each of the following essential MCH services: antenatal care, facility-based delivery, modern contraceptive use, childhood immunisations (BCG, diphtheria, tetanus, pertussis/Pentavalent and measles) and treatments of childhood illnesses (fever, cough and diarrhoea). METHODS: We estimated generalised additive models with logit links and smoothing terms for households' geolocation and survey years. RESULTS: Higher maternal education and households' wealth were significantly associated with utilisation of all types of essential MCH services (p<0.05). On the other hand, households with more children under 5 years of age and in poor communities were significantly less likely to use essential MCH services (p<0.05). Except for childhood immunisations, greater access to transport was positively associated with utilisation (p<0.05). Households with longer travel times to the most accessible health facility were less likely to use all types of essential MCH services (p<0.05), except modern contraceptive use and treatment of childhood fever and/or cough. CONCLUSION: This study adds to the evidence that maternal education and household wealth status are consistently associated with utilisation of essential MCH services across time and space. To increase utilisation of essential MCH services across different geolocations, interventions targeting poor communities and households with more children under 5 years of age should be appropriately designed. Moreover, additional interventions should prioritise to reduce inequities of essential MCH service utilisation between the wealth quantiles and between education status.

Pandemic Politics: Timing State-Level Social Distancing Responses to COVID-19.

CONTEXT: Social distancing is an essential but economically painful measure to flatten the curve of emergent infectious diseases. As the novel coronavirus that causes COVID-19 spread throughout the United States in early 2020, the federal government left to the states the difficult and consequential decisions about when to cancel events, close schools and businesses, and issue stay-at-home orders. METHODS: The authors present an original, detailed dataset of state-level social distancing policy responses to the epidemic; they then apply event history analysis to study the timing of implementation of five social distancing policies across all 50 states. RESULTS: The most important predictor of when states adopted social distancing policies is political: all else equal, states led by Republican governors were slower to implement such policies during a critical window of early COVID-19 response. CONCLUSIONS: Continuing actions driven by partisanship rather than by public health expertise and scientific recommendations may exact greater tolls on health and broader society.

Health facility readiness and facility-based birth in Haiti: a maximum likelihood approach to linking household and facility data.

BACKGROUND: Haiti has one of the world's highest maternal mortality ratios. Comprehensive obstetric services could prevent many of these deaths, though most births in Haiti occur outside health facilities. Demand-side factors like a mother's socioeconomic status are understood to affect her access or choice to deliver in a health facility. However, analyses of the role of supply-side factors like health facility readiness have been constrained by limited data and methodological challenges. We sought to address these challenges and determine whether Haiti could increase rates of facility-based birth by improving facility readiness to provide delivery services. METHODS: Our task was to characterize facility delivery readiness and link it to nearby births. We used birth data from the 2012 Haiti DHS and facility data from the 2013 Haiti SPA. Our outcome of interest was facility-based birth. Our predictor of interest was delivery readiness at the DHS sampling cluster level. We derived a novel likelihood function that used Kernel Density Estimation to estimate cluster-level readiness alongside the coefficients of a logistic regression. RESULTS: We analyzed data from 389 facilities and 1,991 births. Rural facilities were less ready than urban facilities to provide delivery services. Women delivering in health facilities were younger, more educated, wealthier, less likely to live in rural areas, and had fewer previous children. Our model estimated that rural facilities (σ = 12.28, standard error [SE] = 0.16) spread their readiness over larger areas than urban facilities (σ = 7.14, SE = 0.016). Cluster-level readiness was strongly associated with facility-based birth (adjusted log-odds = 0.031; p = 0.005), as was socioeconomic status (adjusted log-odds = 0.78; p < 0.001). CONCLUSIONS: Health system policymakers in Haiti could increase rates of facility-based birth by supporting targeted interventions to improve facility readiness to provide delivery-related services, alongside efforts to reduce poverty and increase educational attainment among women.

State government organization of health services, 1990-2009: correlates and consequences.

OBJECTIVES: To describe changes in the organizational structure of state health-related departments/agencies between 1990 and 2009; to identify factors associated with key organizational structures; and to investigate their relationship with different resource allocations across health policy areas, as represented by state budgets. DESIGN: Original data collection on the organization of state health-related departments/agencies from 1990 to 2009. Analyses included descriptive statistics, logistic regression, and time-series regression modeling. SETTING AND PARTICIPANTS: All 50 states. MAIN OUTCOMES MEASURES: Organizational structure of state government related to health in 4 areas (Medicaid, public health, mental health, human services); coupling of Medicaid and public health in the same agency; state budget changes in health policy areas, including Medicaid, public health, and hospitals. RESULTS: The housing of 2 or more health-related functions in the same unit was common, with 21 states combining public health and Medicaid at 1 or more points in time. Eighteen states (36%) reorganized their health agencies/departments during the study period. Controlling for numerous economic, social, and political factors, when the state agency responsible for public health is consolidated with Medicaid, the share of the state budget allocated to Medicaid declined significantly, while public health allocations were unchanged. However, consolidating Medicaid with other services did not impact state Medicaid spending. CONCLUSIONS: Government organizational structure related to health varies greatly across states and is somewhat dynamic. When Medicaid and public health functions are consolidated in the same stage agency, public health does not "lose" in terms of its share of the state budget. However, this could change as Medicaid costs continue to grow and with the implementation the Patient Protection and Affordable Care Act of 2010.

Allocation of authority in European health policy.

Although many study the effects of different allocations of health policy authority, few ask why countries assign responsibility over different policies as they do. We test two broad theories: fiscal federalism, which predicts rational governments will concentrate information-intensive operations at lower levels, and redistributive and regulatory functions at higher levels; and "politicized federalism", which suggests a combination of systematic and historically idiosyncratic political variables interfere with efficient allocation of authority. Drawing on the WHO Health in Transition country profiles, we present new data on the allocation of responsibility for key health care policy tasks (implementation, provision, finance, regulation, and framework legislation) and policy areas (primary, secondary and tertiary care, public health and pharmaceuticals) in the 27 EU member states and Switzerland. We use a Bayesian multinomial mixed logit model to analyze how different countries arrive at different allocations of authority over each task and area of health policy, and find the allocation of powers broadly follows fiscal federalism. Responsibility for pharmaceuticals, framework legislation, and most finance lodges at the highest levels of government, acute and primary care in the regions, and provision at the local and regional levels. Where allocation does not follow fiscal federalism, it appears to reflect ethnic divisions, the population of states and regions, the presence of mountainous terrain, and the timing of region creation.