Cost-Effectiveness of Respiratory Syncytial Virus Preventive Interventions in Children: A Model Comparison Study.

OBJECTIVES: Model-based cost-effectiveness analyses on maternal vaccine (MV) and monoclonal antibody (mAb) interventions against respiratory syncytial virus (RSV) use context-specific data and produce varied results. Through model comparison, we aim to characterize RSV cost-effectiveness models and examine drivers for their outputs. METHODS: We compared 3 static and 2 dynamic models using a common input parameter set for a hypothetical birth cohort of 100 000 infants. Year-round and seasonal programs were evaluated for MV and mAb interventions, using available evidence during the study period (eg, phase III MV and phase IIb mAb efficacy). RESULTS: Three static models estimated comparable medically attended (MA) cases averted versus no intervention (MV, 1019-1073; mAb, 5075-5487), with the year-round MV directly saving ∼€1 million medical and €0.3 million nonmedical costs, while gaining 4 to 5 discounted quality-adjusted life years (QALYs) annually in <1-year-olds, and mAb resulting in €4 million medical and €1.5 million nonmedical cost savings, and 21 to 25 discounted QALYs gained. In contrast, both dynamic models estimated fewer MA cases averted (MV, 402-752; mAb, 3362-4622); one showed an age shift of RSV cases, whereas the other one reported many non-MA symptomatic cases averted, especially by MV (2014). These differences can be explained by model types, assumptions on non-MA burden, and interventions' effectiveness over time. CONCLUSIONS: Our static and dynamic models produced overall similar hospitalization and death estimates, but also important differences, especially in non-MA cases averted. Despite the small QALY decrement per non-MA case, their larger number makes them influential for the costs per QALY gained of RSV interventions.

Expected Impact of Universal Immunization With Nirsevimab Against RSV-Related Outcomes and Costs Among All US Infants in Their First RSV Season: A Static Model.

BACKGROUND: Respiratory syncytial virus (RSV) is associated with substantial morbidity in the United States, especially among infants. Nirsevimab, an investigational long-acting monoclonal antibody, was evaluated as an immunoprophylactic strategy for infants in their first RSV season and for its potential impact on RSV-associated, medically attended lower respiratory tract illness (RSV-MALRTI) and associated costs. METHODS: A static decision-analytic model of the US birth cohort during its first RSV season was developed to estimate nirsevimab's impact on RSV-related health events and costs; model inputs included US-specific costs and epidemiological data. Modelled RSV-related outcomes included primary care and emergency room visits, hospitalizations including intensive care unit admission and mechanical ventilations, and RSV-related mortality. RESULTS: Under current standard of care, RSV caused 529 915 RSV-MALRTIs and 47 281 hospitalizations annually, representing $1.2 billion (2021 US dollars [USD]) in costs. Universal immunization of all infants with nirsevimab is expected to reduce 290 174 RSV-MALRTI, 24 986 hospitalizations, and expenditures of $612 million 2021 USD. CONCLUSIONS: An all-infant immunization strategy with nirsevimab could substantially reduce the health and economic burden for US infants during their first RSV season. While this reduction is driven by term infants, all infants, including palivizumab-eligible and preterm infants, would benefit from this strategy.

Potential Impact of Nirsevimab on RSV Transmission and Medically Attended Lower Respiratory Tract Illness Caused by RSV: A Disease Transmission Model.

INTRODUCTION: Respiratory syncytial virus (RSV) is associated with significant morbidity worldwide, especially among infants. We evaluated the potential impact of prophylactic nirsevimab, a monoclonal antibody, in infants experiencing their first RSV season, and the number of medically-attended lower respiratory tract infection episodes caused by RSV (RSV-MALRTI) in the USA. METHODS: We developed an age-structured, dynamic, deterministic compartmental model reflecting RSV natural history, incorporating USA demographic data and an age-specific contact matrix. We assumed either no effect of nirsevimab on transmission (scenario 1) or a 50% reduction of viral shedding (scenario 2). Model outcomes were RSV-MALRTIs, ICD-9 coded in the Marketscan® database by month. We focused on age groups corresponding to the first 2 years of life, during seven RSV seasons (2008-2015). RESULTS: Scenario 1 illustrated the direct individual benefit when a universal immunization strategy is applied to all infants. In scenario 2, herd protection was observed across age groups, with 15.5% of all avoided cases due to reduced transmission; the greatest impact was in the youngest age group and a benefit was observed in those aged 65+ years. CONCLUSION: These preliminary data suggest that single-dose nirsevimab will benefit infants experiencing their first RSV season, with a potential increase in effectiveness dependent on nirsevimab's mechanism of action.

Incidence of respiratory syncytial virus related health care utilization in the United States.

BACKGROUND: Respiratory Syncytial Virus (RSV) is one of the most frequent causes of acute respiratory infection worldwide. Understanding age-specific health care utilization is necessary to guide effective prevention strategies. This retrospective database analysis assessed the incidence rates of RSV-related health care utilization in the USA over a 7-year period. METHODS: Episodes of RSV were identified in the Truven Health MarketScan® Commercial Claims and Encounters database between 2008 and 2014 using ICD-9-CM codes for pneumonia, bronchiolitis and RSV (480-486, 487.0, 466.1, 491.2, 079.6). Annual RSV-related health care utilization was calculated for the total population, by age group (<1, 1, 2-4, 5-17, 18-49, 50-64, 65-74, 75-84 and ≥85 years) and the proportion of cases for each setting (hospitalization, outpatient, or emergency department [ED] / urgent care [UC]). RESULTS: Over the 7-year study period, the mean rate of all RSV-associated health care utilization was 2.4 per 1000 person-years, with mean rates ranging from 2.0 to 2.6). The highest rate was seen in infants aged <1 year (mean 79.0 per 1000 over the 7-year period), which decreased with increasing age in the range 2-49 years before increasing with age in older adults (mean rate 8.1 per 1000 over the 7-year period in those ≥85 years). Of all RSV cases, 82% were reported in an outpatient setting, 11% in the ED/UC and 7% were hospitalized. CONCLUSIONS: The annual RSV-related healthcare utilization rates were substantial, especially in infants and young children. These results underscore the need to accelerate the development of RSV prevention strategies to reduce the healthcare burden of RSV.

Cost of Respiratory Syncytial Virus-Associated Acute Lower Respiratory Infection Management in Young Children at the Regional and Global Level: A Systematic Review and Meta-Analysis.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infection (ALRI) in young children aged <5 years. METHODS: We aimed to identify the global inpatient and outpatient cost of management of RSV-ALRI in young children to assist health policy makers in making decisions related to resource allocation for interventions to reduce severe morbidity and mortality from RSV in this age group. We searched 3 electronic databases including Global Health, Medline, and EMBASE for studies reporting cost data on RSV management in children under 60 months from 2000 to 2017. Unpublished data on the management cost of RSV episodes were collected through collaboration with an international working group (RSV GEN) and claim databases. RESULTS: We identified 41 studies reporting data from year 1987 to 2017, mainly from Europe, North America, and Australia, covering the management of a total of 365 828 RSV disease episodes. The average cost per episode was €3452 (95% confidence interval [CI], 3265-3639) and €299 (95% CI, 295-303) for inpatient and outpatient management without follow-up, and it increased to €8591(95% CI, 8489-8692) and €2191 (95% CI, 2190-2192), respectively, with follow-up to 2 years after the initial event. CONCLUSIONS: Known risk factors (early and late preterm birth, congenital heart disease, chronic lung disease, intensive care unit admission, and ventilator use) were associated with €4160 (95% CI, 3237-5082) increased cost of hospitalization. The global cost of inpatient and outpatient RSV ALRI management in young children in 2017 was estimated to be approximately €4.82 billion (95% CI, 3.47-7.93), 65% of these in developing countries and 55% of global costs accounted for by hospitalization. We have demonstrated that RSV imposed a substantial economic burden on health systems, governments, and the society.

The Public Health Benefits and Economic Value of Routine Yellow Fever Vaccination in Colombia.

OBJECTIVES: To evaluate the public health benefits and economic value of live-attenuated yellow fever (YF) 17D vaccine in Colombia. METHODS: A decision tree model was used to assess the theoretical impact of routine YF vaccination of 1-year-olds (no "catch-up") during the interepidemic period from 1980 to 2002, avoiding capturing the impact of YF vaccine introduction in 2003. The vaccine was assumed to be 99% effective, to provide lifetime protection, and to cover 85% of the target population. Costs per disability-adjusted life-year (DALY) averted were computed from payer and societal perspectives. Univariate sensitivity analyses were performed. RESULTS: During the interepidemic period, routine YF vaccination would have averted 2223 nonfatal cases of YF and 65 deaths, leading to an overall reduction of 1365 DALYs. The net cost of this vaccination would have been $25 964 813 (payer's perspective) and $16 535 465 (societal perspective). Cost per DALY averted was $19 022 and $12 114 from payer and societal perspectives, respectively (all costs in 2015 US dollars). Vaccination was considered cost-effective from both perspectives (ie, between 1- and 3-fold the gross domestic product per capita, $7158) and remains so if price per dose was $2.75 or less and $4.66 from payer and societal perspectives, respectively. Underreporting had the largest impact on the results. CONCLUSIONS: Routine toddler YF vaccination in Colombia would have been considered cost-effective in the prevaccination era. This study provides insights on the value of vaccination in an upper middle-income country.

Trends in healthcare utilization and costs associated with pneumonia in the United States during 2008-2014.

BACKGROUND: Pneumonia is the leading cause of morbidity and mortality worldwide. Pneumococcal conjugate vaccines have reduced the burden of pneumonia, but data on the current burden of pneumonia and its impact on the healthcare system are needed to inform the development and use of new vaccines and other preventive measures. METHODS: We retrospectively analyzed the frequency of pneumonia in the US during 2008-2014 using data from the MarketScan® Commercial Claims and Encounters database. Frequencies of healthcare utilization related to the index pneumonia episode were calculated using the annual number of enrolled person-years (PY) as the denominator and the number of individuals with pneumonia as the numerator. Pneumonia-associated costs were calculated as mean payment per episode during the 2 years from 2013 to 2014. RESULTS: The overall annual healthcare utilization rate for pneumonia was 15.1 per 1000 PY and decreased slightly from 2008 to 2014 (from 15.4 to 13.5 per 1000 PY). Most pneumonia-related healthcare utilization was due to office/outpatient visits (10.3 per 1000 PY; 68.3%). Emergency department/urgent care visits (2.5 per 1000 PY; 16.9%) and hospitalizations (2.2 per 1000 PY; 14.8%) contributed less. Pneumonia-related healthcare utilization was highest in children < 5 years (rate per 1000 PY = 29.7 for < 1 year, 47.9 for 1 year, and 39.5 for 2-4 years) and adults > 65 years (45.0 per 1000 PY). The mean cost per pneumonia episode (95% confidence interval) was US$429.1 ($424.8-$433.4) for office/outpatient visits, $1126.9 ($1119.5-$1134.3) for emergency department/urgent care visits, and $10,962.5 ($10,822.8-$11,102.2) for hospitalization. CONCLUSIONS: The burden of pneumonia on the US healthcare system remains substantial. The results presented here can help guide new vaccination strategies and other preventive interventions for reducing the remaining burden of pneumonia.

Trends in healthcare utilization and costs associated with acute otitis media in the United States during 2008-2014.

BACKGROUND: Acute otitis media (AOM) is the most common cause of pediatric medical visits and antibiotic prescriptions worldwide, but its current impact on the US healthcare system is not clear. The aim of this study was to investigate changes in the incidence of AOM from 2008, just before 13-valent pneumococcal conjugate vaccine was introduced, to 2014 using US insurance records in the Truven MarketScan® database. The study also examined the costs associated with index AOM events during the two most recent years for which data were available (2013-2014). METHODS: AOM cases in the MarketScan database during 2008-2014 were identified using ICD9 diagnosis codes 381.xx and 382.xx. Incidence rates of healthcare utilization related to the index AOM episode were calculated using the annual number of enrolled person-years as the denominator and the number of individuals with AOM as the numerator. AOM-associated costs were calculated as the mean payment per episode during the 2 years from 2013 to 2014. RESULTS: The overall annual rate of AOM-related healthcare utilization was 60.5 per 1000 person-years and changed little from 2008 to 2014 (range, 58.4-62.6). Most of this was due to office/outpatient visits (55.7 [range, 52.0-58.8] per 1000 person-years). Emergency department/urgent care visits (4.7 [range 3.7-6.3] per 1000 person-years) and hospitalization (0.0 [range, 0.0-0.1] per 1000 person-years) contributed little. The rate of AOM-related healthcare utilization per 1000 person-years was highest in the youngest children and declined with age (474.3 for < 1 year, 503.9 for 1 year, 316.3 for 2-4 years, 94.9 for 5-17 years, 33.1 for 18-49 years, 28.6 for 50-64 years, 23.7 for 65-74 years, 20.2 for 75-84 years, and 16.1 for ≥85 years). The mean cost per AOM episode in 2013-2014 (95% confidence interval) was $199.0 (198.4-199.6) for office or outpatient visits, $329.6 (328.2-331.0) for emergency department/urgent care visits, and $1592.9 (1422.0-1763.8) for hospitalization. CONCLUSIONS: In the US, AOM-associated healthcare utilization and costs remain substantial. More effective preventive measures such as new vaccines are needed to reduce the burden of AOM.

Healthcare resource use and economic burden attributable to respiratory syncytial virus in the United States: a claims database analysis.

BACKGROUND: Despite several studies that have estimated the economic impact of Respiratory Syncytial Virus (RSV) in infants, limited data are available on healthcare resource use and costs attributable to RSV across age groups. The aim of this study was to quantify age-specific RSV-related healthcare resource use and costs on the US healthcare system. METHODS: This retrospective case-control study identified patients aged ≥1 year with an RSV event in the Truven Health Marketscan® Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases between August 31, 2012 and August 1, 2013. RSV patients were matched 1:1 with non-RSV controls for age, gender, region, healthcare plan and index date (n = 11,432 in each group). Stratified analyses for healthcare resource use and costs were conducted by age groups. RSV-attributable resource use and costs were assessed based on the incremental differences between RSV cases and controls using multivariate analysis. RESULTS: RSV patients had a higher healthcare resource use (hospital stays, emergency room/urgent care visits, ambulatory visits and outpatient visits) than non-RSV matched controls for all age groups (all p < 0.0001), particularly in the elderly age groups with RSV (1.9 to 3 days length of stay, 0.4 to 0.5 more ER/UC visits, 0.7 to 2.7 more ambulatory visits, 12.1 to 18.6 more outpatient visits and 9.5 to 14.6 more prescriptions than elderly in the control groups). The incremental difference in adjusted mean annual costs between RSV and non-RSV controls was higher in elderly (≥65; $12,030 to $23,194) than in those aged < 65 years ($2251 to $5391). Among children, adjusted costs attributable to RSV were higher in children aged 5-17 years ($3192), than those 1-4 years ($2251 to $2521). CONCLUSIONS: Our findings showed a substantial annual RSV-attributable healthcare resource use and costs in the US across age groups, with the highest burden in those aged ≥65 years. These data can be used in cost-effectiveness analyses, and may be useful for policymakers to guide future RSV vaccination and other prevention programs.

Protecting children from rabies with education and pre-exposure prophylaxis: A school-based campaign in El Nido, Palawan, Philippines.

BACKGROUND: Rabies remains endemic in the Philippines. A study was conducted in El Nido, Palawan, Philippines to: (i) detect the true incidence of animal bites in school children aged 5-14 years using active surveillance and compare these data to estimates from the existing passive surveillance system, (ii) evaluate the impact of rabies prevention education and pre-exposure prophylaxis (PrEP) on animal bite incidence, and (iii) assess the health economic impact of the interventions. METHODOLOGY AND PRINCIPAL FINDINGS: A cohort of 4,700 school children was followed-up for any suspect rabies exposures between January 2011 and December 2012. Data on animal bite incidence from the study cohort were compared to that obtained from a review of consultation records at the Animal Bite Treatment Center (ABTC). PrEP was offered to children in all 27 public elementary schools in El Nido (in January to February 2012). Teachers were given a manual for integrating rabies in the public elementary school curriculum during the school year 2012-13. Active surveillance of the cohort revealed a higher incidence of suspect rabies exposures than that from passive surveillance. Despite a decrease in the number of Category III bites, there was no significant decrease in overall bite incidence as a result of the interventions. However, there was an increase in rabies awareness among school children in all grade levels. There was also a high level of acceptability of PrEP. Children who received PrEP and subsequently were bitten only needed two booster doses for post-exposure prophylaxis, resulting in substantial cost-savings. CONCLUSIONS/SIGNIFICANCE: The true burden of animal bites remains underestimated in ABTC records. PrEP is advantageous in selected population groups, i.e. school-aged children in rabies endemic areas with limited access to animal and human rabies prevention services. Educating school children is beneficial. Strengthening veterinary interventions to target the disease at source is important.

Estimating the global burden of endemic canine rabies.

BACKGROUND: Rabies is a notoriously underreported and neglected disease of low-income countries. This study aims to estimate the public health and economic burden of rabies circulating in domestic dog populations, globally and on a country-by-country basis, allowing an objective assessment of how much this preventable disease costs endemic countries. METHODOLOGY/PRINCIPAL FINDINGS: We established relationships between rabies mortality and rabies prevention and control measures, which we incorporated into a model framework. We used data derived from extensive literature searches and questionnaires on disease incidence, control interventions and preventative measures within this framework to estimate the disease burden. The burden of rabies impacts on public health sector budgets, local communities and livestock economies, with the highest risk of rabies in the poorest regions of the world. This study estimates that globally canine rabies causes approximately 59,000 (95% Confidence Intervals: 25-159,000) human deaths, over 3.7 million (95% CIs: 1.6-10.4 million) disability-adjusted life years (DALYs) and 8.6 billion USD (95% CIs: 2.9-21.5 billion) economic losses annually. The largest component of the economic burden is due to premature death (55%), followed by direct costs of post-exposure prophylaxis (PEP, 20%) and lost income whilst seeking PEP (15.5%), with only limited costs to the veterinary sector due to dog vaccination (1.5%), and additional costs to communities from livestock losses (6%). CONCLUSIONS/SIGNIFICANCE: This study demonstrates that investment in dog vaccination, the single most effective way of reducing the disease burden, has been inadequate and that the availability and affordability of PEP needs improving. Collaborative investments by medical and veterinary sectors could dramatically reduce the current large, and unnecessary, burden of rabies on affected communities. Improved surveillance is needed to reduce uncertainty in burden estimates and to monitor the impacts of control efforts.

Modeling the long-term persistence of hepatitis A antibody after a two-dose vaccination schedule in Argentinean children.

BACKGROUND: Long-term seroprotection data are essential for decision-making on the need and timing of vaccine boosters. Based on data from longitudinal serological studies, modeling can provide estimates on long-term antibody persistence and inform such decision-making. METHODS: We examined long-term anti-hepatitis A virus (anti-HAV) antibody persistence in Argentinean children ≤15 years after the initial study where they completed a 2-dose course of inactivated hepatitis A vaccine (Avaxim 80U Pediatric, Sanofi Pasteur, Lyon, France). Blood serum samples were taken at baseline, 2 weeks (post first dose), 6 months (pre-booster), 6.5 months (post-booster), 10 years and 14-15 years after first vaccine dose. We fitted 8 statistical model types, predominantly mixed effects models, to anti-HAV persistence data, to identify the most appropriate and best fitting models for our data set and to predict individuals' anti-HAV levels and seroprotection rates up to 30 years post vaccination. RESULTS: Fifty-four children (mean age at enrollment 30.4 months) were enrolled up to 15 years post first vaccine dose. There were 3 distinct periods of antibody concentration: rapid rise up to peak concentration post-booster, rapid decay from post-booster to 10 years, followed by slower decay. A 3-segmented linear mixed effects model was the most appropriate for the data set. Extrapolating based on the available 14-15-year follow-up, the analysis predicted that 88% of individuals anti-HAV seronegative prior to vaccination would remain seroprotected at 30 years post vaccination and lifelong seroprotection for vaccinees seropositive prior to vaccination. CONCLUSIONS: Currently available data demonstrate that Avaxim 80U Pediatric confers to most vaccinees a high level of seroprotection against hepatitis A infection for at least 20-30 years.

A sero-epidemiological study of arboviral fevers in Djibouti, Horn of Africa.

Arboviral infections have repeatedly been reported in the republic of Djibouti, consistent with the fact that essential vectors for arboviral diseases are endemic in the region. However, there is a limited recent information regarding arbovirus circulation, and the associated risk predictors to human exposure are largely unknown. We performed, from November 2010 to February 2011 in the Djibouti city general population, a cross-sectional ELISA and sero-neutralisation-based sero-epidemiological analysis nested in a household cohort, which investigated the arboviral infection prevalence and risk factors, stratified by their vectors of transmission. Antibodies to dengue virus (21.8%) were the most frequent. Determinants of infection identified by multivariate analysis pointed to sociological and environmental exposure to the bite of Aedes mosquitoes. The population was broadly naïve against Chikungunya (2.6%) with risk factors mostly shared with dengue. The detection of limited virus circulation was followed by a significant Chikungunya outbreak a few months after our study. Antibodies to West Nile virus were infrequent (0.6%), but the distribution of cases faithfully followed previous mapping of infected Culex mosquitoes. The seroprevalence of Rift valley fever virus was 2.2%, and non-arboviral transmission was suggested. Finally, the study indicated the circulation of Toscana-related viruses (3.7%), and a limited number of cases suggested infection by tick-borne encephalitis or Alkhumra related viruses, which deserve further investigations to identify the viruses and vectors implicated. Overall, most of the arboviral cases' predictors were statistically best described by the individuals' housing space and neighborhood environmental characteristics, which correlated with the ecological actors of their respective transmission vectors' survival in the local niche. This study has demonstrated autochthonous arboviral circulations in the republic of Djibouti, and provides an epidemiological inventory, with useful findings for risk mapping and future prevention and control programs.

Determinants of individuals' risks to 2009 pandemic influenza virus infection at household level amongst Djibouti city residents--a CoPanFlu cross-sectional study.

BACKGROUND: Following the 2009 swine flu pandemic, a cohort for pandemic influenza (CoPanFlu) study was established in Djibouti, the Horn of Africa, to investigate its case prevalence and risk predictors' at household level. METHODS: From the four city administrative districts, 1,045 subjects from 324 households were included during a face-to-face encounter between 11th November 2010 and 15th February 2011. Socio-demographic details were collected and blood samples were analysed in haemagglutination inhibition (HI) assays. Risk assessments were performed in a generalised estimating equation model. RESULTS: In this study, the indicator of positive infection status was set at an HI titre of ≥ 80, which was a relevant surrogate to the seroconversion criterion. All positive cases were considered to be either recent infections or past contact with an antigenically closely related virus in humans older than 65 years. An overall sero-prevalence of 29.1% and a geometrical mean titre (GMT) of 39.5% among the residents was observed. Youths, ≤ 25 years and the elderly, ≥65 years had the highest titres, with values of 35.9% and 29.5%, respectively. Significantly, risk was high amongst youths ≤ 25 years, (OR 1.5-2.2), residents of District 4(OR 2.9), students (OR 1.4) and individuals living near to river banks (OR 2.5). Belonging to a large household (OR 0.6), being employed (OR 0.5) and working in open space-outdoor (OR 0.4) were significantly protective. Only 1.4% of the cohort had vaccination against the pandemic virus and none were immunised against seasonal influenza. CONCLUSION: Despite the limited number of incident cases detected by the surveillance system, A(H1N1)pdm09 virus circulated broadly in Djibouti in 2010 and 2011. Age-group distribution of cases was similar to what has been reported elsewhere, with youths at the greatest risk of infection. Future respiratory infection control should therefore be tailored to reach specific and vulnerable individuals such as students and those working in groups indoors. It is concluded that the lack of robust data provided by surveillance systems in southern countries could be responsible for the underestimation of the epidemiological burden, although the main characteristics are essentially similar to what has been observed in developed countries.

2009 A(H1N1) seroconversion rates and risk factors among the general population in Vientiane Capital, Laos.

OBJECTIVE: To assess 2009 A(H1N1) seroconversion rates and their determinants within an unvaccinated population in Vientiane Capital, Laos. METHODS: CoPanFlu Laos, a general population cohort of 807 households and 4,072 participants was established in March 2010. Sociodemographic data, epidemiological data, and capillary blood samples were collected from all the household members in March, and again in October 2010, in order to assess the level of antibodies to 2009 A(H1N1) with the haemagglutination inhibition assay. 2009 A(H1N1) seroconversion was defined as a fourfold or greater increase in titre between inclusion and follow-up. Determinants for pandemic influenza infection were studied using the generalized estimating equations model, taking household clustering into account. RESULTS: Between March and November 2010, 3,524 paired sera were tested. Prior to the pandemic, our cohort was almost completely vaccine-naive for seasonal influenza. The overall seroconversion rate among nonvaccinated individuals (n = 2,810) was 14.3% (95%CI [13.0, 15.6]), with the highest rate for participants under 20 yo (19.8%, 95%CI [17.4, 22.4]) and the lowest rate for participants over 60 yo (6.5%, 95%CI [3.7, 10.4]). Participants with lower baseline titres had significantly higher infection rates, with a dose-effect relationship. Odds ratios (ORs) ranged from 76.5 (95%CI [27.1, 215.8]), for those with a titre at inclusion of 1∶10, to 8.1 (95%CI [3.3, 20.4]), for those with a titre of 1∶40. Having another household member with a titre ≥1∶80 was associated with a higher likelihood of immunity (OR = 3.3, 95%CI [2.8, 3.9]). CONCLUSION: The determinants and age distribution for seroconversion within a vaccine-naive population were similar to those found in developed countries. This pandemic was characterized by strong epidemiological determinants, regardless of geographical zone and level of development. Moreover, we detected pre-existing cross-reacting antibodies in participants over 60 yo, which could not have originated from former multiple vaccination as has been suggested elsewhere.

Correlates of LDL-cholesterol goal attainment in patients under lipid lowering therapy.

BACKGROUND: LDL-cholesterol therapeutic objectives attainment under lipid lowering therapy remains inadequate. The correlates of LDL-cholesterol therapeutic objective attainment have not been thoroughly explored in an observational setting. METHODS: Patients under lipid lowering therapy and managed by general practitioners were included. LDL-cholesterol therapeutic objective was defined according to the number of cardiovascular risk factors associated with dyslipidemia (AFSSAPS-2005 guidelines). RESULTS: Most of the 2727 patients (mean age: 64.7+/-11.0) received a statin (70.0%) or a fibrate (24.3%) in monotherapy. 58.5% of patients at high cardiovascular risk did not reach therapeutic objective. Compared to simvastatin, patients receiving fibrates were less likely to be at therapeutic objective (OR=0.38, 95% CI=[0.26-0.54]). So were patients receiving fluvastatin (OR=0.41, IC95%=[0.26-0.64]) or pravastatin (OR=0.49, IC95%=[0.35-0.70]) at the dosages used by GPs. No significant difference appeared with atorvastatin (OR=0.99, 95% CI=[0.71-1.39]) or rosuvastatin (OR=1.25, CI95%=[0.77-2.02]). Patients with LDL-cholesterol levels<0.7 g/L tended to be prescribed high doses of lipid lowering therapy. CONCLUSIONS: In real conditions of lipid lowering therapy use, LDL-cholesterol therapeutic objective attainment was inadequate in high-risk patients, and TO differences were observed between drugs at prescribed doses.

Baseline results of the Depiscan study: a French randomized pilot trial of lung cancer screening comparing low dose CT scan (LDCT) and chest X-ray (CXR).

BACKGROUND: Lung cancer has the highest mortality-rate per cancer, with an overall 5-year survival <15%. Several non-randomized studies pointed out the high sensitivity of low dose computed tomography (LDCT) to detect early stage lung cancer. In France, Depiscan, a pilot RCT of LDCT versus chest X-ray (CXR), started on October 2002 to determine the feasibility of enrollment by general practitioners (GPs), investigations and diagnostic procedures by university hospital radiologists and multidisciplinary teams, data management by centralized clinical research assistants, and anticipate the future management of a large national trial. METHODS: GPs and occupational physicians (OPs) selected and enrolled 1000 subjects in 1 year. Eligible subjects were asymptomatic males or females aged 50-75 years with a current or former cigarette smoking history of >/=15 cigarettes per day for at least 20 years (former smokers having quit <15 years prior to enrollment). Based to randomization, annual LDCT or CXR screenings were planned at baseline and annually for 2 years. RESULTS: Between October 2002 and December 2004, 765 subjects were enrolled by 89 out of the 232 participating GPs and OPs. Complete clinical and imaging baseline data were available for 621 individuals out of the 765 enrolled, due to 144 noncompliant subjects who withdrew their consent. At least one nodule was detected in 152 out of 336 subjects (45.2%) in the LDCT screening, versus 21 out of 285 subjects (7.4%) in the CXR screening arm. Eight lung cancers were detected in the LDCT arm and one in the CXR arm. DISCUSSION: This pilot trial allows estimating that non-calcified nodules are 10 [6.36-17.07] times more often detected from LDCT than from CXR. However enrollment by GPs was more difficult than expected with 41% active investigators and a high rate (19%) of noncompliant patients. This experience speaks to the need for a high level of GPs formation and a large, coordinated clinical research team in such a trial. TRIAL REGISTRATION NUMBER: 02526.