Cost-effectiveness analysis measuring the total costs against the health benefits of three different rotavirus vaccines for Mexico.

Rotavirus (RV) infection causes acute rotavirus gastroenteritis (RVGE) in infants. Safe and effective RV vaccines are available, of which Mexico has included one in its national immunization program (NIP) since 2007. Health outcome gains, expressed in quality-adjusted life years (QALYs), and cost improvements are important additional factors for the selection of a NIP vaccine. These two factors were analyzed here for Mexico over one year implementing three RV vaccines: 2-dose Rotarix (HRV), versus 3-dose RotaTeq (HBRV), and 3-dose Rotasiil (BRV-PV), presented in a 1-dose or 2-dose vial). HRV would annually result in discounted QALY gains of 263 extra years compared with the other vaccines by averting an extra 24,022 homecare cases, 10,779 medical visits, 392 hospitalizations, and 12 deaths. From a payer's perspective and compared with HRV, BRV-PV 2-dose vial and BRV-PV 1-dose vial would annually result in $13,548,179 and $4,633,957 net savings, respectively, while HBRV would result in $3,403,309 extra costs. The societal perspective may also show savings compared with HRV for BRV-PV 2-dose vial of $4,875,860, while BRV-PV 1-dose vial and HBRV may show extra costs of $4,038,363 and $12,075,629 respectively. HRV and HBRV were both approved in Mexico, with HRV requiring less investment than HBRV with higher QALY gains and cost savings. The HRV vaccine produced those higher health gains due to its earlier protection and greater coverage achieved after its schedule completion with two doses only, providing full protection at four months of age instead of longer periods for the other vaccines.

Rotavirus (RV) infection causes acute diarrhea in infants and can be life-threatening. Several safe and effective vaccines against RV and its complications exist. For many governments choosing vaccines for national immunization programs, total costs or savings and health gains are important factors in the selection process. We compared the costs and health benefits of three RV vaccines for Mexico: HRV, HBRV, and BRV-PV, that have different dosing schedules: two doses for HRV and three doses for HBRV and BRV-PV. HRV is currently part of the national immunization program in Mexico. HRV would result in more health benefits as it incurs fewer RV-related cases, medical visits, hospitalizations, and infant deaths than the other vaccines due to its early protection achieved after only two doses to complete its schedule. However, from a payer's perspective, the least expensive vaccine was BRV-PV, while HRV was less expensive than HBRV. From a societal perspective, also accounting for families' costs and loss in income due to an infant's RV disease, and the families' costs and loss in income when accompanying the infant to the vaccination center, the HRV vaccine was less expensive than HBRV and BRV-PV presented in a 1-dose vial, while more expensive than BRV-PV presented in a 2-dose vial. HRV and HBRV are both approved in Mexico, although HBRV requires a greater investment at lower health benefits than HRV, from both a payer's and a societal perspective. A 2-dose vaccination scheme is an important asset for the economic value of this vaccination program.

Activación Hemisférica Cerebral en Adultos Jóvenes Mientras Ejecutan Tareas Ortográficas Utilizando fMRI / Hemispheric Brain Activation in Young Adults While Performing Orthographic Tasks Using fMRI

Resumen El dominio del lenguaje escrito se basa en la consolidación de representaciones neurales complejas de los patrones ortográficos de las palabras. En virtud de explorar las características presentes en procesos neurales relacionados con la especialización ortográfica, se estudiaron con métodos de imagen por resonancia magnética funcional los niveles neurales de activación intrahemisférica de 27 jóvenes con alto y bajo rendimiento ortográfico mientras ejecutaban tareas ortográficas. Los resultados sugieren que, en participantes con alto rendimiento ortográfico, la intensidad de activación neural en el hemisferio izquierdo no difiere ante el estímulo de palabras o pseudohomófonos (palabras con error ortográfico); en cambio, difieren cuando se emiten respuestas correctas vs. incorrectas. En participantes con bajo rendimiento ortográfico no se encontró diferencia interhemisférica en ninguna tarea. Se encontró tendencia de que los participantes con bajo rendimiento ortográfico tienen mayor dispersión de la activación neural, respecto a los participantes con alto rendimiento, en el hemisferio derecho e izquierdo, además, en participantes con bajo rendimiento ortográfico se encontró tendencia de que la detección consciente aumenta la variación de la activación neural; sin embargo, no se encontró evidencia estadística concluyente. Este estudio ha abonado a la evidencia de la existencia de la especialización neural orientada a habilidades ortográficas.

Abstract The written language domain is based on the consolidation of complex neural representations of words' orthographic patterns. Here, we studied the characteristics and differences of the neural activation levels that occur in the neural processes related to orthographic specialization, with functional magnetic resonance imaging, in each hemisphere, of 27 young adults with low and high orthographic abilities when they performed orthographic tasks. The results suggest that in high-orthographic-performance participants' left hemispheric neural activation does not vary between words and pseudohomophones; otherwise, their neural activation variates in incorrect vs. correct responses. There were not found interhemispheric differences in low-orthographic-performance participants where they performed any type of task. There were some tendency in the low-orthographic-performance participants to have greater neural activation dispersion, regarding the high-orthographic-performance participants, in both hemispheres, also, there were found tendency in low-orthographic-performance participants to have greater neural activation variation in explicit tasks; nevertheless, there is not enough conclusive statistic evidence. This study increases the evidence of lateralized neural specialization of orthographic abilities.

Risk of Intussusception After Rotavirus Vaccination: Meta-analysis of Postlicensure Studies.

BACKGROUND: Postlicensure surveillance studies suggest a small temporal increase in the risk for intussusception with both currently available rotavirus vaccines (RV1; Rotarix, GSK and RV5; RotaTeq, Merck & Co., Inc.). This meta-analysis was undertaken to provide a single overall estimate of the relative risk of intussusception during the 7-day period after administration of RV1 and RV5. METHODS: Meta-analysis based on estimates of relative risk and corresponding 95% confidence intervals from 5 postlicensure studies providing an estimate of risk of intussusception during the 7-day period after administration of dose 1 and/or dose 2 of RV1 and/or RV5, based on active and/or passive surveillance, for confirmed intussusception cases (Brighton or other method of case confirmation). For each vaccine, the relative risk of intussusception was estimated postdose 1 and postdose 2. Results were pooled using the inverse variance method using both fixed-effect and random-effect models. RESULTS: The overall estimate of relative risk of intussusception during the 7 days postdose 1 was 5.4 (95% confidence interval: 3.9-7.4, 3 studies) for RV1 and 5.5 (3.3-9.3, 3 studies) for RV5. The overall estimate of relative risk of intussusception during the 7 days postdose 2 was 1.8 (1.3-2.5, 4 studies) for RV1 and 1.7 (1.1-2.6, 3 studies) for RV5. CONCLUSIONS: This meta-analysis showed a similar increased risk of intussusception, during the first 7 days after administration of dose 1 and, to a lesser extent, dose 2, for both currently available rotavirus vaccines. This suggests that intussusception may be a class effect of currently available oral rotavirus vaccines.

[Presentation, staging, and outcome of patients with hepatocellular carcinoma at a center in Veracruz, Mexico]. / Presentación, clasificación y evolución de los pacientes con carcinoma hepatocelular en un centro de Veracruz, México.

BACKGROUND: Hepatocellular carcinoma (HCC) staging provides a basis for calculating disease prognosis and therapeutic guidance. Liver resection and transplantation are curative options, and ablation therapies are applied to patients that are not candidates for curative treatment. Survival after liver resection or ablation therapies varies. AIMS: To describe the presentation, staging, management, and outcome in patients with HCC in our center. PATIENTS AND METHODS: Forty-two patients had a 7-year prospective follow-up. Survival was calculated with the Kaplan-Meier analysis and the log-rank test was used for its comparison between the staging systems (Okuda, BCLC, and CLIP) and types of treatment (liver resection, radiofrequency ablation, and no surgical treatment). RESULTS: The mean age of the patients was 68.9 ± 9.5 years; 57% were women. A total of 54% of the patients presented with cirrhosis and 31% were infected with hepatitis C virus (HCV). The mean tumor size was 6.48 ± 2.52cm. The CLIP 0, Okuda I, and BCLC A stages had better survival rates than the other stages (P<0.05). Survival with resection was superior (median of 32 months and survival at 1, 3, and 5 years of 83, 39, and 19.7%, respectively) to that of both radiofrequency ablation (median of 25 months and survival at 1 and 3 years of 90 and 17.2%, respectively) and no surgical treatment (1 year < 5%) (P<0.05). CONCLUSION: The patients at our center were diagnosed at late stages of HCC, as is the case in other Mexican populations. Outcome in relation to CLIP and BCLC was similar to the prognoses reported in the literature. The best results were observed in the patients with early stage disease and those that underwent HCC resection surgery.

Calidad de vida de la luxación acromioclavicular / Quality of life of patients with acromioclavicular dislocation

Objetivo: Comparar la calidad de vida en pacientes con luxación acromioclavicular tipo III de Tossy tratados mediante técnica RAFI de placa gancho, técnica Weaver Dunn y técnica Bosworth. Material y métodos: Se realizó una encuesta transversal, analítica, de Enero de 2012 a Abril 2013, en pacientes con diagnóstico de luxación acromioclavicular tipo III de Tossy intervenidos con la técnica de RAFI con placa gancho, técnica Weaver y Dunn y técnica de Bosworth. Se incluyeron a los pacientes con edades de entre 18 y 70 años y cirugía realizada dentro de las primeras tres semanas del diagnóstico. El grado de calidad de vida fue evaluado mediante el cuestionario de DASH heteroadministrado, previo consentimiento informado. Resultados: Se operaron 47 pacientes divididos en 3 grupos, técnica RAFI placa gancho 26 pacientes, técnica Weaver y Dunn 11 pacientes y la técnica de Bosworth, 10 pacientes. El sexo y la edad fueron similares en los tres grupos con una p = 0.137 y p = 0.252 respectivamente. El tiempo de evolución de la cirugía fue similar en los tres grupos, con una p = 0.051. La técnica, RAFI placa gancho fue la más empleada con 26 cirugías; 96.4% de pacientes mostró discapacidad leve y síntomas leves con técnica RAFI placa gancho y 100% en la técnica Bosworth y Weaver y Dunn. Conclusiones: La calidad de vida fue similar con las tres técnicas quirúrgicas con una discapacidad y síntomas leves. La técnica RAFI placa gancho fue la más utilizada.

To compare quality of life in patients with Tossy type III acromioclavicular dislocation treated with the hook-plate ORIF technique, the Weaver & Dunn technique and the Bosworth technique. Material and methods: A cross-sectional analytical survey was conducted from January 2012 to April 2013 in patients with a diagnosis of Tossy type III acromioclavicular dislocation treated surgically with the hook-plate ORIF technique, the Weaver & Dunn technique, and the Bosworth technique. We included patients ages 18 to 70 years old, operated within three weeks after the diagnosis. Quality of life was assessed using the hetero-administered DASH questionnaire once the informed consent was obtained. Results: Forty-seven patients were operated on. They were divided into 3 groups: hook-plate ORIF technique, with 26 patients: Weaver & Dunn technique, 11 patients; and Bosworth technique, 10 patients. Sex and age distribution were similar in all 3 groups, with p = 0.137 and p = 0.252, respectively. Time elapsed after surgery was similar in all 3 groups, with p = 0.051. The hook-plate ORIF technique was the most frequently used one, in 26 surgeries. 96.4% of patients had mild disability and symptoms with the hook-plate ORIF technique, and 100% with the Bosworth and Weaver & Dunn techniques. Conclusions: Quality of life was similar with all 3 surgical techniques and involved mild disability and symptoms. The hook-plate ORIF technique was the most frequently used technique.

[Quality of life of patients with acromioclavicular dislocation]. / Calidad de vida de la luxación acromioclavicular.

OBJECTIVE: To compare quality of life in patients with Tossy type Ill acromioclavicular dislocation treated with the hook-plate ORIF technique, the Weaver & Dunn technique and the Bosworth technique. MATERIAL AND METHODS: A cross-sectional analytical survey was conducted from January 2012 to April 2013 in patients with a diagnosis of Tossy type III acromioclavicular dislocation treated surgically with the hook-plate ORIF technique, the Weaver & Dunn technique, and the Bosworth technique. We included patients ages 18 to 70 years old, operated within three weeks after the diagnosis. Quality of life was assessed using the hetero-administered DASH questionnaire once the informed consent was obtained. RESULTS: Forty-seven patients were operated on. They were divided into 3 groups: hook-plate ORIF technique, with 26 patients: Weaver & Dunn technique, 11 patients; and Bosworth technique, 10 patients. Sex and age distribution were similar in all 3 groups, with p =0.137 and p = 0.252, respectively. Time elapsed after surgery was similar in all 3 groups, with p = 0.051. The hook-plate ORIF technique was the most frequently used one, in 26 surgeries. 96.4% of patients had mild disability and symptoms with the hook-plate ORIF technique, and 100% with the Bosworth and Weaver & Dunn techniques. CONCLUSIONS: Quality of life was similar with all 3 surgical techniques and involved mild disability and symptoms. The hook-plate ORIF technique was the most frequently used technique.

Rejection is a strong graft survival predictor in live donor pediatric renal transplantation using cyclosporine, mycophenolate mofetil, and steroids: 5-year outcomes in a single Mexican center.

Long-term graft function and survival are of particular importance in children assuming that they have a longer transplantation life span than most adults. Because acute rejection episodes (ARE) continue to have a serious impact on graft loss, we analyzed the effects of ARE on 5-year survival and function in our population. Fifty-seven living donor kidney transplant recipients (34 males) younger than 18 years of age (13.5 ± 2.6 years; range, 5-17) were follow up for at feast 12 months using cyclosporine, mycophenolate mofetil, and steroid therapy with or without induction treatment between February 2003 and December 2010. ARE incidence during the first 12 months following transplantation was 14%. One-, 3- and 5-year serum creatinine values were 1.24 ± 0.39, 2.16 ± 2.39, and 1.76 ± 0.9 mg/dL, respectively. Mean calculated creatinine clearances (Schwartz) at 1, 3, and 5 years were 82.5 ± 24.8, 64.7 ± 24.1, and 67 ± 27.5 mL/min*1.73 m(2), respectively. Patient/graft survival rates were 96/85%, 90/72%, and 88/65% at 1, 3, and 5 years, respectively. Patients who experienced an ARE within 12 months following transplantation displayed a reduced 5-year graft survival rate (37.5%) versus those who did not (78%; P = .005). Patients who did not have an ARE during 60 months had a higher graft survival rate (76%) than those who had ARE (33%; P = .001). Patient without basiliximab induction showed a lower 5-year graft survival rate (61% vs 100%; P = not significant [NS]). ARE is an important risk factor for graft loss in the pediatric kidney transplant population.

Evaluation of the second generation of a commercial latex agglutination test for the detection of rotavirus antigens in fecal samples.

BACKGROUND: Despite vaccine availability, the infection rate and disease burden associated with rotavirus infection are still high. Thus, accurate diagnosis of rotavirus infection continues to be necessary for proper patient clinical management and disease control. OBJECTIVE: To evaluate the performance of a novel, second generation, commercial latex tests (Pastorex™ Rotavirus latex agglutination test, BIORAD, Marnes-La-Coquette, France), for the detection of rotavirus in human feces. STUDY DESIGN: Using 166 fecal samples collected from children with acute diarrhea, and previously tested for rotavirus, calicivirus and astrovirus, the second generation Pastorex™ Rotavirus latex agglutination test was evaluated. RESULTS AND CONCLUSION: The test showed a sensitivity of 85.9% and a specificity of 97.7%. Positive and negative predicted values for the test were 97% and 88%, respectively. The results suggest that this commercial test is a good alternative for rotavirus diagnosis.

Postmarketing surveillance of intussusception following mass introduction of the attenuated human rotavirus vaccine in Mexico.

BACKGROUND: Mexico initiated mass vaccination with the attenuated human rotavirus vaccine (Rotarix) in 2006. This postlicensure study aimed to assess any potential temporal association between vaccination and intussusception in Mexican infants. METHODS: Prospective, active surveillance for intussusception among infants aged less than 1 year was conducted in 221 hospitals across Mexico from the Mexican Institute of Social Security between January 2008 and October 2010. The temporal association between vaccination and intussusception was assessed by self-controlled case-series analysis. RESULTS: Of the 753 episodes of intussusception reported in 750 infants, 701 were in vaccinated infants (34.5% post-dose 1, 65.5% post-dose 2). The relative incidence of intussusception within 31 days of vaccination was 1.75 (95.5% confidence interval [CI]: 1.24-2.48; P=0.001) post-dose 1 and 1.06 (95.5% CI: 0.75-1.48; P=0.75) post-dose 2. The relative incidence of intussusception within 7 days of vaccination was 6.49 post-dose 1 (95.5% CI: 4.17-10.09; P<0.001) and 1.29 post-dose 2 (95.5% CI: 0.80-2.11; P=0.29). Clustering of intussusception within 7 days of vaccination was observed post-dose 1. An attributable risk of 3 to 4 additional cases of intussusception per 100,000 vaccinated infants was estimated. CONCLUSION: This is the largest surveillance study for intussusception after rotavirus vaccination to date. A temporal increase in the risk for intussusception was seen within 7 days of administration of the first vaccine dose. It is still uncertain whether rotavirus vaccination has any impact on the overall incidence of intussusception. This finding has to be put in perspective with the well-documented substantial benefits of rotavirus vaccination.

Seguridad del neonato hospitalizado: Aproximaciones y propuestas / Safety of hospitalized neonate: Approximations and Proposals

La seguridad del paciente forma parte de las prioridades de los sistemas de salud a nivel mundial. Es a través de la Alianza Mundial por la Seguridad de los Pacientes que la Organización Mundial de la Salud (OMS) planteó el objetivo de prevenir eventos adversos durante la atención de las personas en las instituciones de salud, asegurando así una atención libre de riesgos. El individuo en su etapa de desarrollo neonatal, se encuentra más vulnerable a sufrir lesiones durante su estancia hospitalaria, por lo que existe la necesidad de contar con medidas de seguridad específicas para evitar riesgos durante su cuidado. Conforme a lo anterior se realizan propuestas de lineamientos aplicadas a este grupo etéreo, basadas en las seis Metas Internacionales para la Seguridad del Paciente establecidas por la Organización Mundial de la Salud (OMS). En la búsqueda bibliográfica realizada en bases de datos como: Artemisa en línea, Pubmed, Scielo, Cochrane Plus, se identificaron algunos documentos que hacen referencia a estrategias de seguridad para pacientes neonatos; sin embargo es de importancia se realicen más investigaciones en enfermería para un cuidado seguro a este grupo de pacientes.

Patient safety is a priority of health systems worldwide. Through the World Alliance for Patient Safety, the World Health Organization established the objective of preventing adverse events during the attention of persons in health institutions, thus assuring a risk free attention. The individual in his/her neonatal development is more vulnerable to suffering lesions in his/her hospital stay, and because of this, there is a necessity of having specific safety measures to prevent risks during his/her care. As a result, guidelines proposals related to this group of persons are developed based on the six International Goals for the Patient Safety established by the World Health Organization (WHO). In the literature search in databases such as Artemisa online, Pubmed, Scielo, Cochrane Plus, several documents referencing safety strategies for neonatal patients were identified; however, it is important to do more nursing research in order to achieve a safe care for this group of patients.

The kinase c-Src and the phosphatase TC45 coordinately regulate c-Fos tyrosine phosphorylation and c-Fos phospholipid synthesis activation capacity.

Our previous work showed that in T98G cells, a human glioblastoma multiforme-derived cell line, the association of c-Fos to the endoplasmic reticulum (ER) and consequently, the capacity of c-Fos to activate phospholipid synthesis, is regulated by the phosphorylation state of tyrosine (tyr) residues #10 and #30 of c-Fos. The small amount of c-Fos present in quiescent cells is tyr-phosphorylated, is dissociated from the ER membranes and does not activate phospholipid synthesis. However, on induction of the cell to re-enter growth, c-Fos expression is rapidly induced, it is found dephosphorylated, associated to ER membranes and activating phospholipid synthesis (Portal et al., 2007). Herein, using in vivo and in vitro experimental strategies, we show that the kinase c-Src is capable of phosphorylating tyr residues of c-Fos whereas the phosphatase TC45 T-cell protein-tyr phosphatase (TC-PTP) dephosphorylates them, thus enabling c-Fos/ER association and activation of phospholipid synthesis. Results also suggest that the regulation of the phosphorylation/dephosphorylation cycle of c-Fos occurs at the TC-PTP level: induction of cells to re-enter growth promotes the translocation of TC45 from a nuclear to a cytoplasmic location concomitant with its activation. Activated TC45 in its turn promotes dephosphorylation of pre-formed c-Fos, enabling cells to rapidly activate phospholipid synthesis to respond to its growth demands.

Burden of disease and costs of treating rotavirus diarrhea in Mexican children for the period 2001-2006.

OBJECTIVES: To estimate the health impact and the costs of treatment associated with rotavirus diarrhea in six yearly cohorts (2001-2006) of Mexican infants. METHODS: The perspective of study is from the health care system. We estimated the effect of rotavirus diarrhea on disability adjusted life years (DALYS) and diarrhea treatment costs in hypothetical cohorts of infants who are followed from birth up to five years of age beginning in years from 2001 to 2006. We used information from administrative databases on mortality and health care from the National System of Information on Health and from the Mexican Institute for Social Security to feed a decision analysis to project the burden of disease and costs of treatment. RESULTS: Estimates of DALYS were 19,426 in 2001 and decreased by 28.9% for 2006 meanwhile costs of treatment were relatively constant, estimated at US$ 38.7 million and increased only by 5%. CONCLUSION: Rotavirus diarrhea in Mexican children is a major disease burden, presenting significant treatment costs. Rotavirus diarrhea mortality is decreasing; however this has not led to a steady decrease in treatment costs in the 6 years period of analysis. A sensitivity analysis showed that incidences of rotavirus diarrhea as well as the parameters associated with health-care access were the main factors, which had a significant effect on the projected burden of disease and costs.

Human caliciviruses detected in Mexican children admitted to hospital during 1998-2000, with severe acute gastroenteritis not due to other enteropathogens.

Few studies exist regarding the frequency of human caliciviruses as single etiologic agents in sporadic cases, or in outbreaks occurring in children hospitalized for acute gastroenteritis. In this study, a total of 1,129 children of <5 years of age and hospitalized due to acute diarrhea were enrolled from three main hospitals in Mexico City during a period of 3 years (March 1998 to December 2000). After analyzing all fecal samples for several enteropathogens, 396 stools that remained negative were further screened for human caliciviruses by RT-PCR using a primer set specific to norovirus and sapovirus. Human caliciviruses were detected in 5.6% (22/396) of the children. The minimum incidence rate for 1999 were 5.3% (7/132) for 1999 and 7.8% (13/167) for 2000, since only fecal specimens that tested negative to other enteric pathogens were examined. Positive samples were further characterized using specific GI and GII primers and sequencing. Norovirus GII was detected in 19/22 samples, most of them were GII/4, while sapovirus GI/2 was detected in one sample. Associations between the presence of human calicivirus and clinical and epidemiological data revealed that diarrhea occurred with a seasonal pattern, and that children hospitalized due to human calicivirus disease scored an average of 13 +/- 3.2 (SD) points on the Vesikari scale, which corresponded to severe episodes. These results highlight that human caliciviruses, by themselves, are enteropathogens of acute severe diarrhea among young Mexican children requiring hospitalization and that their detection is important in order to reduce the diagnosis gap.

Economic impact of a rotavirus vaccination program in Mexico.

OBJECTIVES: To evaluate the cost and benefits of a national rotavirus childhood vaccination program in Mexico. METHODS: A decision-analysis model was designed to take the Mexican health care system's perspective on a comparison of two alternatives: to vaccinate against rotavirus or not. Using published, national data, estimations were calculated for the rotavirus illnesses, deaths, and disability-adjusted life years (DALYs) that would be averted and the incremental cost-effectiveness ratios (US$/DALY) of a hypothetical annual birth cohort of 2 285 000 children, with certain assumptions made for cost, coverage, and efficacy rates. RESULTS: With 93% coverage and a vaccine price of US$ 16 per course (2 doses), a rotavirus vaccination program in Mexico would prevent an estimated 651 deaths (or 0.28 deaths per 1 000 children); 13 833 hospitalizations (6.05 hospitalizations per 1 000 children); and 414 927 outpatient visits (182 outpatient visits per 1 000 children) for rotavirus-related acute gastroenteritis (AGE). Vaccination is likely to reduce the economic burden of rotavirus AGE in Mexico by averting US$ 14 million (71% of the overall health care burden). At a vaccine price of US$ 16 per course, the cost-effectiveness ratio would be US$ 1 139 per DALY averted. A reduction in the price of the rotavirus vaccination program (US$ 8 per course) would yield a lower incremental cost-effectiveness ratio of US$ 303 per DALY averted. CONCLUSIONS: A national rotavirus vaccination program in Mexico is projected to reduce childhood incidence and mortality and to be highly cost-effective based on the World Health Organization's thresholds for cost-effective interventions.

Economic impact of a rotavirus vaccination program in Mexico / Impacto económico de un programa de vacunación contra rotavirus en México

OBJECTIVES: To evaluate the cost and benefits of a national rotavirus childhood vaccination program in Mexico. METHODS: A decision-analysis model was designed to take the Mexican health care system's perspective on a comparison of two alternatives: to vaccinate against rotavirus or not. Using published, national data, estimations were calculated for the rotavirus illnesses, deaths, and disability-adjusted life years (DALYs) that would be averted and the incremental costeffectiveness ratios (US$/DALY) of a hypothetical annual birth cohort of 2 285 000 children, with certain assumptions made for cost, coverage, and efficacy rates. RESULTS: With 93 percent coverage and a vaccine price of US$ 16 per course (2 doses), a rotavirus vaccination program in Mexico would prevent an estimated 651 deaths (or 0.28 deaths per 1 000 children); 13 833 hospitalizations (6.05 hospitalizations per 1 000 children); and 414 927 outpatient visits (182 outpatient visits per 1 000 children) for rotavirus-related acute gastroenteritis (AGE). Vaccination is likely to reduce the economic burden of rotavirus AGE in Mexico by averting US$ 14 million (71 percent of the overall health care burden). At a vaccine price of US$ 16 per course, the cost-effectiveness ratio would be US$ 1 139 per DALY averted. A reduction in the price of the rotavirus vaccination program (US$ 8 per course) would yield a lower incremental cost-effectiveness ratio of US$ 303 per DALY averted. CONCLUSIONS: A national rotavirus vaccination program in Mexico is projected to reduce childhood incidence and mortality and to be highly cost-effective based on the World Health Organization's thresholds for cost-effective interventions.

OBJETIVOS: Evaluar el costo y los beneficios de un programa nacional de vacunación infantil contra el rotavirus en México. MÉTODOS: Se diseñó un modelo de análisis de decisión, desde la perspectiva del sistema de salud mexicano, para comparar dos alternativas: vacunar contra el rotavirus o no vacunar. A partir de datos nacionales publicados se estimó el número de casos y muertes por rotavirus, los años de vida ajustados por la discapacidad (AVAD) que se evitarían y la relación costo-efectividad incremental (US$/AVAD) de una cohorte anual hipotética de 2 285 000 niños; se partió de algunos supuestos sobre el costo, la cobertura y las tasas de eficacia. RESULTADOS: Con una cobertura de 93 por ciento y un precio de la vacuna de US$ 16,00 por esquema (dos dosis), se estima que un programa de vacunación contra rotavirus en México evitaría 651 muertes (0,28 muertes por 1 000 niños), 13 833 hospitalizaciones (6,05 hospitalizaciones por 1 000 niños) y 414 927 visitas de consulta externa (182 consultas por 1 000 niños) por gastroenteritis aguda asociada a rotavirus (GAR). La vacunación podría reducir la carga económica por GAR en México al evitar gastos por US$ 14 millones (71 por ciento de la carga total por atención sanitaria). A un precio de US$ 16,00 por esquema, la relación costo-efectividad sería de US$ 1 139,00 por AVAD evitado. Una reducción en el precio del programa de vacunación contra rotavirus (US $8,00 por esquema) generaría una menor relación costo-efectividad incremental de US$ 303,00 por AVAD evitado. CONCLUSIONES: Un programa nacional de vacunación contra rotavirus en México reduciría la incidencia y la mortalidad infantiles y sería altamente efectivo en función del costo, según los umbrales de las intervenciones de costo-efectividad de la Organización Mundial de la Salud.

[Methylphenidate and short-term memory in young females with attention deficit hyperactivity disorder. A study using functional magnetic resonance imaging]. / Metilfenidato y memoria a corto plazo en mujeres jovenes con trastorno por deficit de atencion/hiperactividad. Estudio de resonancia magnetica funcional.

INTRODUCTION: Attention deficit/hyperactivity disorder (ADHD) is a common behavioral disorder found mainly in males, thus current knowledge on its clinical expression in female adults is extremely limited. AIM. To evaluate the behavioral and neural substrates associated with the performance of a short-term memory task in female ADHD adults, with and without methylphenidate exposure, with respect to a control group. SUBJECTS AND METHODS: Two groups of eight young right-handed, female, university students with ADHD and healthy controls matched by age, gender, handedness and academic level, voluntarily participated. All subjects performed twice an easy auditory short-term memory task (ADHD group without, and 90 minutes post-intake of methylphenidate 0.4 mg/kg in a counterbalanced order). The BOLD-fMRI response was used as a measure of neural activity during task performance. RESULTS: ADHD subjects showed a tendency to improve their performances under medication, showing an increased widespread functional activation, especially relevant over left frontal and cerebellar areas, in comparison with control subjects. CONCLUSIONS: Methylphenidate slightly improves short-term memory task performance in adult female ADHD subjects by modifying underlying neural functioning patterns.

Protective effects of natural rotavirus infection.

Rotavirus is a ubiquitous infection that is the leading cause of severe diarrhea worldwide. Severe infections are most commonly observed in the first 2 years of life. Rotavirus-induced diarrhea is associated with substantial morbidity and mortality rates and socioeconomic costs with adverse outcomes particularly prevalent in developing countries. The natural history of rotavirus infection can provide guidance for the development and optimization of an effective vaccine. Epidemiologic studies have demonstrated that children who acquire natural rotavirus infections develop immunity to subsequent infections, with the protective effect increasing with each natural infection. Natural infections also decrease the severity of any subsequent rotavirus infections. Notably, asymptomatic infections provide protection similar to that induced by symptomatic infections. Data also suggest that the antibody response to natural infection is heterotypic, and therefore may provide protection against multiple serotypes. These data suggest that the development of a vaccine that produces asymptomatic infection at an optimal time point may provide effective immunity. An effective vaccine should mimic protection provided by natural infection and provide protection against the most common rotavirus serotypes (ie, G1, G2, G3, G4, G9) and be able to decrease disease severity, reduce hospitalizations, and decrease disease-related costs.

Efficacy and safety of an oral live attenuated human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in Latin American infants: a randomised, double-blind, placebo-controlled phase III study.

BACKGROUND: Peak incidence of rotavirus gastroenteritis is seen in infants between 6 and 24 months of age. We therefore aimed to assess the 2-year efficacy and safety of an oral live attenuated human rotavirus vaccine for prevention of severe gastroenteritis in infants. METHODS: 15 183 healthy infants aged 6-13 weeks from ten Latin American countries randomly assigned in a 1 to 1 ratio to receive two oral doses of RIX4414 or placebo at about 2 and 4 months of age in a double-blind, placebo-controlled phase III study were followed up until about 2 years of age. Primary endpoint was vaccine efficacy from 2 weeks after dose two until 1 year of age. Treatment allocation was concealed from investigators and parents of participating infants. Efficacy follow-up for gastroenteritis episodes was undertaken from 2 weeks after dose two until about 2 years of age. Analysis was according to protocol. This study is registered with ClinicalTrials.gov, number NCT00140673 (eTrack444563-023). FINDINGS: 897 infants were excluded from the according-to-protocol analysis. Fewer cases (p<0.0001) of severe rotavirus gastroenteritis were recorded for the combined 2-year period in the RIX4414 group (32 [0.4%] of 7205; 95% CI 0.3-0.6) than in the placebo group (161 [2.3%] of 7081; 1.9-2.6), resulting in a vaccine efficacy of 80.5% (71.3-87.1) to 82.1% (64.6-91.9) against wild-type G1, 77.5% (64.7-86.2) against pooled non-G1 strains, and 80.5% (67.9-88.8) against pooled non-G1 P[8] strains. Vaccine efficacy for hospital admission for rotavirus gastroenteritis was 83.0% (73.1-89.7) and for admission for diarrhoea of any cause was 39.3% (29.1-48.1). No cases of intussusception were reported during the second year of follow-up. INTERPRETATION: Two doses of RIX4414 were effective against severe rotavirus gastroenteritis during the first 2 years of life in a Latin American setting. Inclusion of RIX4414 in routine paediatric immunisations should reduce the burden of rotavirus gastroenteritis worldwide.

Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis.

BACKGROUND: The safety and efficacy of an attenuated G1P[8] human rotavirus (HRV) vaccine were tested in a randomized, double-blind, phase 3 trial. METHODS: We studied 63,225 healthy infants from 11 Latin American countries and Finland who received two oral doses of either the HRV vaccine (31,673 infants) or placebo (31,552 infants) at approximately two months and four months of age. Severe gastroenteritis episodes were identified by active surveillance. The severity of disease was graded with the use of the 20-point Vesikari scale. Vaccine efficacy was evaluated in a subgroup of 20,169 infants (10,159 vaccinees and 10,010 placebo recipients). RESULTS: The efficacy of the vaccine against severe rotavirus gastroenteritis and against rotavirus-associated hospitalization was 85 percent (P<0.001 for the comparison with placebo) and reached 100 percent against more severe rotavirus gastroenteritis. Hospitalization for diarrhea of any cause was reduced by 42 percent (95 percent confidence interval, 29 to 53 percent; P<0.001). During the 31-day window after each dose, six vaccine recipients and seven placebo recipients had definite intussusception (difference in risk, -0.32 per 10,000 infants; 95 percent confidence interval, -2.91 to 2.18; P=0.78). CONCLUSIONS: Two oral doses of the live attenuated G1P[8] HRV vaccine were highly efficacious in protecting infants against severe rotavirus gastroenteritis, significantly reduced the rate of severe gastroenteritis from any cause, and were not associated with an increased risk of intussusception. (ClinicalTrials.gov numbers, NCT00139347 and NCT00263666.)