Cost-effectiveness analysis of the pediatric 20-valent pneumococcal conjugate vaccine compared with lower-valent alternatives in Argentina.

OBJECTIVES: The 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended for infants in Argentina's national immunization program (NIP) in a 2 + 1 schedule since 2012. Licensure of the 15-valent vaccine (PCV15) is anticipated soon, and the 20-valent vaccine (PCV20) recently received regulatory approval. This cost-effectiveness analysis examined the public health and economic implications of transitioning from PCV13 to either PCV15 or PCV20 in Argentina's pediatric NIP. METHODS: A decision-analytic Markov model was used with a 10-year time horizon and a 3.0% annual discount rate for costs and benefits. Vaccine effectiveness estimates were derived from Argentinian surveillance data, PCV13 clinical effectiveness and impact studies, and PCV7 efficacy studies. Population, epidemiologic, and economic inputs were obtained from literature and Argentinian-specific data. The study adopted a healthcare system perspective; sensitivity and scenario analyses were conducted to assess input parameters and structural uncertainty. RESULTS: Compared with PCV13, PCV20 was estimated to avert an additional 7,378, 42,884, and 172,389 cases of invasive pneumococcal disease (IPD), all-cause pneumonia, and all-cause otitis media (OM), respectively, as well as 3,308 deaths, resulting in savings of United States Dollars (USD) 50,973,962 in direct medical costs. Compared with PCV15, PCV20 was also estimated to have greater benefit, averting an additional 6,140, 35,258, and 142,366 cases of IPD, pneumonia, and OM, respectively, as well as 2,624 deaths, resulting in savings of USD 37,697,868 in direct medical costs. PCV20 was associated with a higher quality-adjusted life year gain and a lower cost (i.e., dominance) versus both PCV13 and PCV15. Results remained robust in sensitivity analyses and scenario assessments. CONCLUSION: Over a 10-year horizon, vaccination with PCV20 was expected to be the dominant, cost-saving strategy versus PCV13 and PCV15 in children in Argentina. Policymakers should consider the PCV20 vaccination strategy to achieve the greatest clinical and economic benefit compared with lower-valent options.

Cost-Effectiveness of 20-Valent Pneumococcal Conjugate Vaccine in Argentinean Adults.

INTRODUCTION: In Argentina, vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23; PCV13 → PPSV23) has been recommended for all adults aged ≥ 65 years and younger adults with chronic medical ("moderate-risk") or immunocompromising ("high-risk") conditions since 2017. With the approval of a 20-valent PCV (PCV20), we evaluated the cost-effectiveness of PCV20 versus current recommendations for moderate-/high-risk adults aged 18-64 years and all adults 65-99 years. METHODS: A probabilistic cohort model was used to project lifetime outcomes and costs associated with invasive pneumococcal disease (IPD) and all-cause non-bacteremic pneumonia (NBP), and the expected impact of vaccination. Clinical outcomes were projected annually based on Argentinean data. Economic costs were estimated based on cases and corresponding medical costs (adjusted to 2023 USD) and costs of vaccine and administration. Cost-effectiveness of PCV20 was evaluated versus the current strategy, PCV13 → PPSV23, and alternatively, versus sequentially administered 15-valent PCV and PPSV23 (PCV15 → PPSV23), and presented as cost per quality-adjusted life year gained; a healthcare system perspective was used. Costs and benefits were discounted at 3%/year. RESULTS: PCV20 in lieu of PCV13 → PPSV23 among moderate-/high-risk adults aged 18-64 years and all adults 65-99 years (N = 13.4M) prevented 3838 IPD, 4377 inpatient NBP, and 6003 outpatient NBP cases, and 1865 disease-related deaths; relative to PCV15 → PPSV23 the corresponding reductions were 2775, 3285, 4518, and 1348. PCV20 was projected to be the dominant strategy versus PCV13 → PPSV23 and PCV15 → PPSV23 as overall costs were lower by $87.6M and $80.8M, respectively. In probabilistic sensitivity analyses, PCV20 was dominant (i.e., more effective, less costly) in 100% of 1000 simulations. CONCLUSIONS: Analyses suggest implementing a PCV20 vaccination program in moderate-/high-risk adults aged 18-64 years and all adults ≥ 65 years-in lieu of PCV13 → PPSV23-would yield substantial reductions in pneumococcal disease and would be cost saving to the Argentinean healthcare system.

Pneumococcal pneumonia has a high disease burden in both children and adults. Older adults and those with certain underlying conditions are more susceptible to severe pneumococcal disease resulting in considerable economic burden on the healthcare system. In Argentina, vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) a year later is recommended for all adults aged ≥ 65 years and adults aged 18­64 years with underlying risk conditions. Despite vaccination efforts, prevalence of pneumococcal disease remains high. Two higher-valent PCVs­15-valent PCV (PCV15) and 20-valent PCV (PCV20)­are available for use in adults with PCV20 offering additional serotype coverage. This study assessed the cost-effectiveness of replacing current (PCV13 → PPSV23) and alternative (PCV15 → PPSV23) vaccination strategies with PCV20 alone. The use of PCV20 was evaluated among Argentinean adults aged 18­64 years with underlying risk conditions and all adults aged 65­99 years (N = 13 million). Over a lifetime time horizon, compared to PCV13 → PPSV23, PCV20 use would avert 14,218 cases and 1865 deaths, and increase quality-adjusted life years by 8655. Compared to PCV15 → PPSV23, PCV20 reduced cases and deaths by 10,578 and 1348, respectively, and increased quality-adjusted life years by 6341. In both comparisons, PCV20 use was cost saving with $87.6 million and $80.8 million lower costs compared to PCV13 → PPSV23 and PCV15 → PPSV23, respectively. Results of the cost-effectiveness analyses suggest that the use of PCV20 is a cost-saving strategy, reducing overall costs to the healthcare system and improving public health.

Implementing Health Technology Assessments in Latin America: Looking at the Past, Mirroring the Future. A Perspective from the ISPOR Health Technology Assessment Roundtable in Latin America.

OBJECTIVES: In the last two decades, several countries in Latin America (LA) have shown an interest in developing health technology assessments (HTAs), but the process has not been uniform and has often been challenged by the health systems characteristics and the political or economic idiosyncrasies of these countries. METHODS: This article summarizes the discussions held by the participants at the 40th ISPOR HTA Council Roundtable for LA. An additional literature review was carried out to support some of the concepts included. RESULTS: This article includes a brief description of the implementation of HTA over the last 30 years and then a conceptual analysis using examples of the broader use of HTA to support procurement decisions and risk-sharing agreements, which might play a future role in healthcare priority-setting in LA. CONCLUSIONS: Formerly, HTA processes and methods played important although mostly isolated roles (with drug licensing or reimbursement being examples of this). Nowadays, with more and more innovative technologies and the establishment of value frameworks to support the priority setting in healthcare, HTA features a promising panorama for the health systems sustainability.

Sequential inactivated (IPV) and live oral (OPV) poliovirus vaccines for preventing poliomyelitis.

BACKGROUND: Poliomyelitis mainly affects unvaccinated children under five years of age, causing irreversible paralysis or even death. The oral polio vaccine (OPV) contains live attenuated virus, which can, in rare cases, cause a paralysis known as vaccine-associated paralytic polio (VAPP), and also vaccine-derived polioviruses (VDPVs) due to acquired neurovirulence after prolonged duration of replication. The incidence of poliomyelitis caused by wild polio virus (WPV) has declined dramatically since the introduction of OPV and later the inactivated polio vaccine (IPV), however, the cases of paralysis linked to the OPV are currently more frequent than those related to the WPV. Therefore, in 2016, the World Health Organization (WHO) recommended at least one IPV dose preceding routine immunisation with OPV to reduce VAPPs and VDPVs until polio could be eradicated. OBJECTIVES: To assess the effectiveness, safety, and immunogenicity of sequential IPV-OPV immunisation schemes compared to either OPV or IPV alone. SEARCH METHODS: In May 2019 we searched CENTRAL, MEDLINE, Embase, 14 other databases, three trials registers and reports of adverse effects on four web sites. We also searched the references of identified studies, relevant reviews and contacted authors to identify additional references. SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-RCTs, controlled before-after studies, nationwide uncontrolled before-after studies (UBAs), interrupted time series (ITS) and controlled ITS comparing sequential IPV-OPV schedules (one or more IPV doses followed by one or more OPV doses) with IPV alone, OPV alone or non-sequential IPV-OPV combinations. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 21 studies: 16 RCTs involving 6407 healthy infants (age range 96 to 975 days, mean 382 days), one ITS with 28,330 infants and four nationwide studies (two ITS, two UBA). Ten RCTs were conducted in high-income countries; five in the USA, two in the UK, and one each in Chile, Israel, and Oman. The remaining six RCTs were conducted in middle-income countries; China, Bangladesh, Guatemala, India, and Thailand. We rated all included RCTs at low or unclear risk of bias for randomisation domains, most at high or unclear risk of attrition bias, and half at high or unclear risk for conflict of interests. Almost all RCTs were at low risk for the remaining domains. ITSs and UBAs were mainly considered at low risk of bias for most domains. IPV-OPV versus OPV It is uncertain if an IPV followed by OPV schedule is better than OPV alone at reducing the number of WPV cases (very low-certainty evidence); however, it may reduce VAPP cases by 54% to 100% (three nationwide studies; low-certainty evidence). There is little or no difference in vaccination coverage between IPV-OPV and OPV-only schedules (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.96 to 1.06; 1 ITS study; low-certainty evidence). Similarly, there is little or no difference between the two schedule types for the number of serious adverse events (SAEs) (RR 0.88, 95% CI 0.46 to 1.70; 4 studies, 1948 participants; low-certainty evidence); or the number of people with protective humoral response P1 (moderate-certainty evidence), P2 (for the most studied schedule; two IPV doses followed by OPV; low-certainty evidence), and P3 (low-certainty evidence). Two IPV doses followed by bivalent OPV (IIbO) may reduce P2 neutralising antibodies compared to trivalent OPV (moderate-certainty evidence), but may make little or no difference to P1 or P2 neutralising antibodies following an IIO schedule or OPV alone (low-certainty evidence). Both IIO and IIbO schedules may increase P3 neutralising antibodies compared to OPV (moderate-certainty evidence). It may also lead to lower mucosal immunity given increased faecal excretion of P1 (low-certainty evidence), P2 and P3 (moderate-certainty evidence) after OPV challenge. IPV-OPV versus IPV It is uncertain if IPV-OPV is more effective than IPV alone at reducing the number of WPV cases (very low-certainty evidence). There were no data regarding VAPP cases. There is no clear evidence of a difference between IPV-OPV and OPV schedules for the number of people with protective humoral response (low- and moderate-certainty evidence). IPV-OPV schedules may increase mean titres of P1 neutralising antibodies compared to OPV alone (low- and moderate-certainty evidence), but the effect on P2 and P3 titres is not clear (very low- and moderate-certainty evidence). IPV-OPV probably reduces the number of people with P3 poliovirus faecal excretion after OPV challenge with IIO and IIOO sequences (moderate-certainty evidence), and may reduce the number with P2 (low-certainty evidence), but not with P1 (very low-certainty evidence). There may be little or no difference between the schedules in number of SAEs (RR 0.92, 95% CI 0.60 to 1.43; 2 studies, 1063 participants, low-certainty evidence). The number of persons with P2 protective humoral immunity and P2 neutralising antibodies are probably lower with most sequential schemes without P2 components (i.e. bOPV) than with trivalent OPV or IVP alone (moderate-certainty evidence). IPV (3)-OPV versus IPV (2)-OPV One study (137 participants) showed no clear evidence of a difference between three IPV doses followed by OPV and two IPV doses followed by OPV, on the number of people with P1 (RR 0.98, 95% CI 0.93 to 1.03), P2 (RR 1.00, 95% CI 0.97 to 1.03), or P3 (RR 1.01, 95% CI 0.97 to 1.05) protective humoral and intestinal immunity; all moderate-certainty evidence. This study did not report on any other outcomes. AUTHORS' CONCLUSIONS: IPV-OPV compared to OPV may reduce VAPPs without affecting vaccination coverage, safety or humoral response, except P2 with sequential schemes without P2 components, but increase poliovirus faecal excretion after OPV challenge for some polio serotypes. Compared to IPV-only schedules, IPV-OPV may have little or no difference on SAEs, probably has little or no effect on persons with protective humoral response, may increase neutralising antibodies, and probably reduces faecal excretion after OPV challenge of certain polio serotypes. Using three IPV doses as part of a IPV-OPV schedule does not appear to be better than two IPV doses for protective humoral response. Sequential schedules during the transition from OPV to IPV-only immunisation schedules seems a reasonable option aligned with current WHO recommendations. Findings could help decision-makers to optimise polio vaccination policies, reducing inequities between countries.

Reparación Endovascular para Aneurisma de Aorta: Revisión Panorámica Sobre su Evidencia en el Mundo y su Aplicación en Latinoamérica.

BACKGROUND: Aortic aneurysm (AA) is a pathology with high morbidity and mortality. The management can be expectant, surgical, or through endovascular repair (EVAR). In Latin America the incidence of AA has increased and the analysis of therapeutic options, especially if they are expensive, is fundamental. OBJECTIVE: To analyze available evidence on the effectiveness, safety and coverage policies of the EVAR. METHODOLOGY: Panoramic review in the main bibliographical bases (MEDLINE, LILACS, EMBASE, Cochrane Library, DARE) and generic internet searchers, main health technology assessment (HTA) agencies and health insurance companies. Systematic reviews (SR), clinical practice guidelines (CPG), HTA and coverage policies, followed by the identification of primary studies published after the SR search date were included. A search of studies published until November 2015 in English and Spanish was carried out. RESULTS: 311 references were recovered, from which seven SRs were selected, one clinical study and 15 CPGs, consensus or coverage policies and ETS. CONCLUSIONS: For abdominal AA, high quality evidence showed no differences inlong-term survival with the use of EVAR compared to conventional surgery, but lower early mortality was observed (OR = 0.33, 95% CI 0.20 -0.55). EVAR was associated with a greater need for re-intervention. In the case of other types of AA, further evidence is still required to establish the benefit of EVAR. The CPGs, consensus, HTAs and coverage policies identified, mostly consider open surgery as the treatment of choice, reserving the EVAR for patients with high surgical risk for conventional surgery in the presence of favorable anatomy.

Burden of Culture-Confirmed Pediatric Pneumococcal Pneumonia in Latin America and the Caribbean: A Systematic Review and Meta-Analysis.

BACKGROUND: Pneumococcal pneumonia (PP) causes almost one in five deaths in children younger than 5 years worldwide. In Latin America and the Caribbean (LAC), pneumonia causes 14% of all deaths. Although pneumococcal disease is a vaccine-preventable disease that accounts for a significant proportion of this burden, the decision-making process to introduce pneumococcal conjugate vaccines in official schedules is still complex in LAC. Confirmed PP cases and epidemiology are the basis for broader projections. OBJECTIVE: To gather all the information available in the LAC region to assist decision makers. METHODS: We performed a systematic review of studies of consolidating and culture-confirmed pediatric PP in LAC (2000-2016) using a generic academic Internet search and search engines without language restrictions. Pairs of reviewers independently selected and assessed the studies' methodological quality. We analyzed meta-information on pneumococcal serotypes available from the SIREVA laboratory-based surveillance system. RESULTS: A total of 35 out of 750 initially identified studies were included. In the age group between 0 and 59 years, the incidence of culture-confirmed PP ranged from 10.2 to 43.0/100,000 children, with a pooled incidence of 20.4/100,000 children (95% confidence interval 0.0-123.2). Mortality ranged from 0.4 to 5.7/100,000 children, and the pooled mortality was 2.9/100,000 children (95% confidence interval 0.3-8.2). The pooled serotype distribution from surveillance data showed that serotypes 14, 1, and 6B were the most frequent serotypes in LAC, all included in licensed vaccines. CONCLUSIONS: Studies on confirmed pediatric PP were scarce in LAC in 2000 to 2016. Epidemiology indicators and health resource use are still poorly defined.

Interchangeability between Pneumococcal Conjugate Vaccines: A Systematic Review and Meta-Analysis.

OBJECTIVES: To assess the efficacy, cost-effectiveness, immunogenicity, and safety related to the interchangeability between pneumococcal conjugate vaccines (PCVs) and vaccination schedules in pediatric population. METHODS: Systematic searches were conducted in December 2010 and April 2015 for economic evaluations in MEDLINE, EMBASE, LILACS, and Cochrane Central Register of Controlled Trials. Web sites and databases from medical societies, experts, and associations related to the topic, proceedings or congressional annals, and doctoral theses were also searched. No language or temporal restriction was applied. We included randomized controlled trials, economic evaluations, and systematic reviews evaluating antibody response, cost-effectiveness, and effectiveness of PCVs' interchangeability. A Strengthening the Reporting of Observational Studies in Epidemiology-based checklist was used to assess the risk of bias in observational studies and a Cochrane approach for experimental/quasi-experimental studies. Pairs of reviewers independently selected (through the Web-based Early Reviewer Organizer Software), assessed the quality, and extracted the data of the studies. Discrepancies were resolved by consensus. We planned to perform meta-analysis whenever appropriate. RESULTS: Forty-six of 202 studies were included. There was no direct information available on the interchangeability between PCVs. The immunogenicity and safety between the 10-valent PCV (PCV10) and the 7-valent PCV were similar when both vaccines were coadministered with other routine pediatric vaccines. PCV10 and 13-valent PCV (PCV13) were consistently more cost-effective than 7-valent PCV. CONCLUSIONS: There was no direct comparative information available on the interchangeability among PCVs, but they have pretty similar immunogenicity and safety. PCV10 versus PCV13 cost-effectiveness varied according to price, indirect effects, and indirect costs. PCV10 gains more quality-adjusted life-years because of the prevention of more frequent yet less severe events such as otitis media, and PCV13 prevents less frequent but more costly events such as invasive diseases.

Medical devices: from licensing to coverage. highlights from Argentina, Brazil, Colombia and Mexico.

OBJECTIVES: To describe and compare the requirements for medical devices licensing and reimbursement in four Latin-American countries. METHODS: We conducted a literature search in major databases, and generic Internet engines, and interviewed key informants. RESULTS: We included all publications describing regulation and/or coverage and enriched them with key informant's interviews. We found that licensing processes are similar. The decision-making process for coverage is not formally different than the one used for drugs. Although countries differ, Brazil, Colombia and Mexico have an explicit process informed by Health Technology Assessment. In general, coverage policies are defined for procedures and don´t specify device brand or model, and for that reason they may reimburse without explicit one by one device evaluation. CONCLUSIONS: The process for licensing and reimbursement is broadly similar but less stringent than that for drugs. It allows the adoption of medical devices without individual comprehensive assessment.

An EQ-5D-5L value set based on Uruguayan population preferences.

PURPOSE: To derive a value set from Uruguayan general population using the EQ-5D-5L questionnaire and report population norms. METHODS: General population individuals were randomly assigned to value 10 health states using composite time trade off and 7 pairs of health states through discrete choice experiments. A stratified sampling with quotas by location, gender, age and socio-economic status was used to respect the Uruguayan population structure. Trained interviewers conducted face-to-face interviews. The EuroQol valuation technology was used to administer the protocol as well as to collect the data. OLS and maximum likelihood robust regression models with or without interactions were tested. RESULTS: We included 794 respondents between 20 and 83 years. Their characteristics were broadly similar to the Uruguayan population. The main effects robust model was chosen to derive social values. Values ranged from -0.264 to 1. States with a misery index = 6 had a mean predicted value of 0.965. When comparing the Uruguayan population with the Argentinian EQ-5D-5L crosswalk value set, the prediction for states which differed from full health only in having one of the dimensions at level 2 were about 0.05 higher in Uruguay. The mean index value, using the selected Uruguayan EQ-5D-5L value set, for the general population in Uruguay was 0.895. In general, older people had worse values and males had slightly better values than females. CONCLUSION: We derived the EQ-5D-5L Uruguayan value set, the first in Latin America. These results will help inform decision-making using economic evaluations for resource allocation decisions.

[Cost-effectiveness of quadrivalent vaccine against human papilloma virus in Argentina based on a dynamic transmission model]. / Costo-efectividad de la vacuna tetravalente contra VPH en Argentina, a partir de un modelo dinámico de transmisión.

OBJECTIVE: To assess the cost-effectiveness of the quadrivalent vaccine against human papillomavirus (HPV) in Argentina from the health system perspective. MATERIALS AND METHODS: A dynamic transmission model was used to estimate the impact of the vaccine on the incidence of cervical cancer, warts, and other HPV related diseases; in quality adjusted life years (QALYs); and in healthcare costs. RESULTS: Vaccination could reduce the risk of cervical cancer by 60% and by 67% the risk of genital warts. Compared to a non-vaccine scenario, the immunization strategy showed an incremental benefit of 0.00234 QALY per person at an incremental cost of US$2.36, resulting in an incremental cost-effectiveness ratio of US$1007.55 per QALY gained. Sensitivity analysis proved the robustness of these results. CONCLUSIONS: Immunization with the quadrivalent vaccine was a cost-effective intervention in Argentina, and it was far below the threshold of one gross domestic product per capita (US$15 009) per QALY gained.

Costo-efectividad de la vacuna tetravalente contra VPH en Argentina, a partir de un modelo dinámico de transmisión / Cost-effectiveness of quadrivalent vaccine against human papilloma virus in Argentina based on a dynamic transmission model

Objetivo. Evaluar la costo-efectividad (CE) de la vacuna tetravalente contra el virus de papiloma humano (VPH) en Argentina, desde la perspectiva del sistema de salud. Material y métodos. Se utilizó un modelo dinámico de transmisión para estimar el impacto en la incidencia de cáncer de cuello uterino (Cacu), verrugas y otras lesiones, en los años de vida ajustados por calidad (AVAC) y en costos sanitarios. Resultados. La vacuna podría reducir en 60% el riesgo de muerte por Cacu y en 67% el de padecer verrugas genitales. Comparada con no vacunar, la estrategia de vacunación mostró un beneficio incremental promedio de 0.00234 AVAC por persona a un costo incremental de 2.36 dólares, con una CE de 1007.55 dólares por AVAC ganado. Los resultados demostraron ser robustos en el análisis de sensibilidad. Conclusiones. La inmunización resultaría costo-efectiva, con una CE inferior a un producto interno bruto per cápita (15 009 dólares) por AVAC ganado.

Objective. To assess the cost-effectiveness of the quadrivalent vaccine against human papillomavirus (HPV) in Argentina from the health system perspective. Materials and methods. A dynamic transmission model was used to estimate the impact of the vaccine on the incidence of cervical cancer, warts, and other HPV related diseases; in quality adjusted life years (QALYs); and in healthcare costs. Results. Vaccination could reduce the risk of cervical cancer by 60% and by 67% the risk of genital warts. Compared to a non-vaccine scenario, the immunization strategy showed an incremental benefit of 0.00234 QALY per person at an incremental cost of US$2.36, resulting in an incremental cost-effectiveness ratio of US$1007.55 per QALY gained. Sensitivity analysis proved the robustness of these results. Conclusions. Immunization with the quadrivalent vaccine was a cost-effective intervention in Argentina, and it was far below the threshold of one gross domestic product per capita (US$15 009) per QALY gained.

Epidemiology of Malaria in Latin America and the Caribbean from 1990 to 2009: Systematic Review and Meta-Analysis.

OBJECTIVE: The objective of this study was to evaluate the burden of malaria in Latin America and the Caribbean countries through a systematic review and meta-analysis of published literature, gray literature, and information from countries' public health authorities for the period 1990 to 2009. METHODS: The random-effects meta-analysis of the prospective studies, carried out in very highly endemic areas, showed an annual incidence rate of 409.0 malaria episodes/1000 person-years (95% confidence interval [CI] 263.1-554.9), considering all ages, which was 40-fold the one estimated from areas with passive surveillance only. RESULTS: Overall, the most prevalent species was Plasmodium vivax (77.5%; 95% CI 75.6-79.4) followed by Plasmodium falciparum (20.8%; 95% CI 19.0-22.6) and Plasmodium malariae (0.08%; 95% CI 0.07-0.010). Data from regional ministries of health yielded an estimated pooled crude annual mortality rate of 6 deaths/100,000 people, mainly associated with P. falciparum. CONCLUSION: This study represents the first systematic review of the burden of malaria in Latin America and the Caribbean, with data from 21 countries.

Systematic review and meta-analysis of respiratory syncytial virus infection epidemiology in Latin America.

Respiratory syncytial virus (RSV) is a frequent cause of acute respiratory infection and the most common cause of bronchiolitis in infants. The aim of this systematic review and meta-analysis was to obtain a comprehensive epidemiological picture of the data available on disease burden, surveillance, and use of resources in Latin America. Pooled estimates are useful for cross-country comparisons. Data from published studies reporting patients with probable or confirmed RSV infection in medical databases and gray literature were included from 74 studies selected from the 291 initially identified. When considering all countries, the largest pooled percentage RSV in low respiratory tract infection patients was found in the group between 0 and 11 months old, 41.5% (95% CI 32.0­51.4). In all countries, percentages were increasingly lower as older children were included in the analyses. The pooled percentage of RSV in LRTIs in the elderly people was 12.6 (95% CI 4.2­24.6). The percentage of RSV infection in hospitalized newborns was 40.9% (95% CI 28.28­54.34). The pooled case fatality ratio for RSV infection was 1.74% (95% CI 1.2­2.4) in the first 2 years of life. The average length of stay excluding intensive care unit admissions among children with risk factors for severe disease was 12.8 (95% CI 8.9­16.7) days, whereas it averaged 7.3 (95% CI 6.1/8.5) days in otherwise healthy children.We could conclude that infants in their first year of age were the most vulnerable population. To our knowledge, this is the first systematic review on RSV disease burden and use of health resources in Latin America.

Lead versus lag-time trade-off variants: does it make any difference?

OBJECTIVES: The traditional time trade-off (TTO) method has some problems in the valuation of health states considered worse than dead. The aim of our study is to compare two TTO variants that address this issue: lead-time and lag-time TTO. METHODS: Quota sampling was undertaken in June 2011 in Buenos Aires as part of the EQ-5D-5L Multinational Pilot Study. Respondents were randomly assigned to one of the TTO variants with two blocks of five EQ-5D-5L health states. Tasks were administered using a web-based digital aid (EQ-VT) administered in a group interview. RESULTS: A total of 387 participants were included [mean age 38.85 (SD: 13.97); 53.14 % females]. The mean observed values ranged from 0.44 (0.59) for state 21111 to 0.02 (0.76) for state 53555 in the lead-time group and between 0.53 (0.52) and 0.08 (0.76) in the lag-time group. There were no statistically significant differences in the values between TTO variants, except for a significant difference of 0.19 for state 33133. In both variants, marked peaks were observed around the value 0 across all states, with a higher percentage of 0 responses in the last state valued, suggesting ordering effects. CONCLUSIONS: No important differences were found between TTO variants regarding values for EQ-5D-5L health states, suggesting that they could be equivalent variants. However, differences between the two methods may have been obscured by other aspects of the study design affecting the characteristics of the data.

Dengue Epidemiology and Burden of Disease in Latin America and the Caribbean: A Systematic Review of the Literature and Meta-Analysis.

INTRODUCTION: Dengue virus infection is the most common arthropod-borne disease worldwide with approximately 50 to 100 million cases of dengue infection occurring annually. Globally, dengue incidence has increased in the last 40 years, especially in Latin American and Caribbean (LAC) countries where the highest incidence is found. This systematic review aimed to present information on dengue disease burden and use of health resources in the LAC region in the last 15 years. METHODS: We searched the main international and regional databases and generic and academic Internet search engines. Gray literature was retrieved mainly from regional health ministries and Pan American Health Organization. A set of inclusion criteria was defined. RESULTS: We identified 2,041 articles of which 25 met these criteria, 13 for incidence and 12 for the use of resources and related costs. The pooled incidence of classic dengue fever was 72.1 cases per 100,000 persons-years in the 44 LAC countries analyzed (95% confidence interval 71.5-72.7), with an upward trend from 1995 up to 2010. Case-fatality ratio was highest in 1997 (0.12 [0.05-0.22]) and lowest in 2009, and the overall mortality was 0.02 per 100,000 people. More than 60% of the cases in the LAC region came from Brazil. The length of hospital stay ranged from 5 to 13 days. CONCLUSIONS: Activities to control dengue transmission in the region have been important but insufficient. The surveillance of dengue burden of disease and circulating strains help shape and evaluate the present and future health policies.

Atlas Argentino de Calidad de Vida Relacionada con la Salud: Análisis de los datos de la Encuesta Nacional de Factores de Riesgo por Provincias.

OBJECTIVE: To describe general population health related quality of life (HRQOL) in Argentina and perform an Atlas showing the country's results using data from the first "National Risk Factors Survey" and local social values. METHODS: Secondary cross-sectional study analyzing EQ-5D-3L responses. The variables of interest were self-reported visual analog scale in a 0-1 scale (SR-VAS), as well as time-trade off (TTO) and VAS preference values (PV). PV were assigned using weights derived from a previous local study. RESULTS: The survey included 41.392 subjects; the expanded population represented 96% of the adult population of Argentina. 8.82% of the population reported excellent health, 24.6% very good, 43.9% good and 22.3% regular or bad. 42.8% reported limitations in at least one of the EQ-5D domain. SR-VAS had a mean of 0.75 (IC95% 0.75-0.76), while general population mean social TTO and VAS based weights were 0.90 (0.898-0.905) and 0.87 (IC95% 0.867-0.874) respectively. The Atlas showed small differences among the provinces. CONCLUSIONS: This is a population based study aimed to describe in depth the HRQOL based in EQ-5D using local PV. It summarizes country level and geographic levels within the country, and constitutes a valuable resource and a starting point for future studies.

Efficacy and safety of human papilloma virus vaccine in cervical cancer prevention: systematic review and meta-analysis.

INTRODUCTION: Cervical cancer is the third most common cancer worldwide. The human papilloma virus (HPV) has been identifed as the etiologic agent of cervical and other anogenital cancers. The aim was to perform a systematic review and meta-analysis to evaluate the efficacy and safety of HPV vaccines in preventing cervical intraepithelial neoplasias (CIN) grades 2 and 3, adenocarcinoma in situ (CIN2+) and cervical cancer. MATERIALS AND METHODS: Major bibliographic databases were searched in July 2011 without any temporal nor language restrictions. Randomized controlled trials that evaluated the efficacy of HPV vaccines against CIN2+ and cervical cancer were included. RESULTS: Four of the 168 publications found were included in a meta-analysis. Among vaccinated women, the relative risk (RR) of developing CIN2+ lesions was 0.45 (95% CI 0.38 to 0.54) for HPV 16, 0.14 (0.08 to 0.25) for HPV 18, and 0.79 (0.68 to 0.93) for oncogenic serotypes not included in the vaccines 31/33/45/52/58. All studies had acceptable safety profiles. CONCLUSIONS: Vaccines currently available are effective, safe and capable of preventing CIN2+ lesions, although long term efficacy has not yet been fully tested.

Efficacy and safety of human papilloma virus vaccine in cervical cancer prevention: systematic review and meta-analysis / Eficacia y seguridad de la vacuna contra el virus de papiloma humano para la prevención del cáncer de cuello uterino: revisión sistemática y metaanálisis

Introduction. Cervical cancer is the third most common cancer worldwide. The human papilloma virus (HPV) has been identifed as the etiologic agent of cervical and other anogenital cancers. The aim was to perform a systematic review and meta-analysis to evaluate the efficacy and safety of HPV vaccines in preventing cervical intraepithelial neoplasias (CIN) grades 2 and 3, adenocarcinoma in situ (CIN2+) and cervical cancer. Materials and Methods. Major bibliographic databases were searched in July 2011 without any temporal nor language restrictions. Randomizedcontrolled trials that evaluated the efficacy of HPV vaccines against CIN2+ and cervical cancer were included. Results. Four of the 168 publications found were included in a meta-analysis. Among vaccinated women, the relative risk (RR) of developing CIN2+ lesions was 0.45 (95% CI 0.38 to 0.54) for HPV 16, 0.14 (0.08 to 0.25) for HPV 18, and 0.79 (0.68 to 0.93) for oncogenic serotypes not included in the vaccines 31/33/45/52/58. All studies had acceptable safety profiles. Conclusions. Vaccines currently available are effective, safe and capable of preventing CIN2+ lesions, although long term efficacy has not yet been fully tested.

Introducción. El cáncer de cuello uterino es el tercer tipo de cáncer en frecuencia en el mundo. El virus de papiloma humano (HPV, por su sigla en inglés) se ha identificado como causa de éste y otros cánceres anogenitales. El objetivo del presente trabajo es evaluar, mediante una revisión sistemática y metaanálisis, la eficacia y seguridad de las vacunas contra HPV para la prevención de neoplasias intraepiteliales (CIN) de grados 2, 3 y adenocarcinoma in situ (CIN2+) y el cáncer de cuello uterino. Materiales y métodos. Se realizó una búsqueda sistemática en las principales bases de datos durante julio de 2011 sin restricciones temporales o idiomáticas. Se incluyeron ensayos clínicos controlados aleatorizados que evaluaran la eficacia de la vacuna contra el desarrollo de CIN2 + y cáncer de cuello uterino. Resultados. Se confeccionó un metaanálisis con 4 de las 168 publicaciones halladas. Mediante el análisis por intención de tratar se observó, para mujeres vacunadas, un riesgo relativo (RR) de contraer lesiones CIN2+ asociadas a HPV 16 de 0,45 (IC 95% 0,38-0,54); a HPV 18 de 0,14 (0,08-0,25) y por serotipos oncogénicos 31/33/45/52/58 no incluidos en la vacuna de 0,79 (0,68-0,93). Todos los estudios mostraron perfiles de seguridad aceptables. Conclusiones. Las vacunas disponibles actualmente mostraron ser eficaces y seguras para la prevención de lesiones CIN2+; sin embargo, resta probar su eficacia a largo plazo.