Immunogenicity and safety of a tetravalent dengue vaccine in dengue-naïve adolescents in Mexico City.

OBJECTIVE: To describe the immunogenicity and safety of a tetravalent dengue vaccine (TAK-003) in healthy adolescents living in Mexico City, an area considered non-endemic for dengue (NCT03341637). METHODS: Participants aged 12-17 years were randomized 3:1 to receive two doses (Month 0 and Month 3) of TAK-003 or placebo. Immunogenicity was assessed by microneutralization assay of dengue neutralizing antibodies at baseline, Months 4 and 9. Solicited and unsolicited adverse events (AEs) were recorded after each vaccination. Serious (SAEs) and medically-attended AEs (MAAEs) were recorded throughout the study. RESULTS: 400 adolescents were enrolled, 391 (97.8%) completed the study. Thirty-six (9%) were baseline seropositive to ≥1 serotypes (reciprocal titer ≥10). Geometric mean titers (GMTs) in baseline seronegative TAK-003 recipients were 328, 1743, 120, and 143 at Month 4, and 135, 741, 46, and 38 at Month 9 against DENV-1, -2, -3, and -4, respectively. Placebo GMTs remained <10. Tetravalent seropositivity rates in vaccine recipients were 99.6% and 85.8% at Months 4 and 9, respectively. One MAAE in each group was considered treatment-related (TAK-003: injection-site erythema, and placebo: pharyngitis). CONCLUSION: TAK-003 was immunogenic against all four serotypes and was well tolerated in dengue-naïve adolescents living in Mexico City.

Immunogenicity and safety of a tetravalent dengue vaccine in dengue-naïve adolescents in Mexico City

[ABSTRACT]. Objective. To describe the immunogenicity and safety of a tetravalent dengue vaccine (TAK-003) in healthy adolescents living in Mexico City, an area considered non-endemic for dengue (NCT03341637). Methods. Participants aged 12–17 years were randomized 3:1 to receive two doses (Month 0 and Month 3) of TAK-003 or placebo. Immunogenicity was assessed by microneutralization assay of dengue neutralizing antibodies at baseline, Months 4 and 9. Solicited and unsolicited adverse events (AEs) were recorded after each vaccination. Serious (SAEs) and medically-attended AEs (MAAEs) were recorded throughout the study. Results. 400 adolescents were enrolled, 391 (97.8%) completed the study. Thirty-six (9%) were baseline seropositive to ≥1 serotypes (reciprocal titer ≥10). Geometric mean titers (GMTs) in baseline seronegative TAK-003 recipients were 328, 1743, 120, and 143 at Month 4, and 135, 741, 46, and 38 at Month 9 against DENV-1, -2, -3, and -4, respectively. Placebo GMTs remained <10. Tetravalent seropositivity rates in vaccine recipients were 99.6% and 85.8% at Months 4 and 9, respectively. One MAAE in each group was considered treatment-related (TAK-003: injection-site erythema, and placebo: pharyngitis). Conclusion. TAK-003 was immunogenic against all four serotypes and was well tolerated in dengue-naïve adolescents living in Mexico City.

[RESUMEN]. Objetivo. Describir la inmunogenicidad y la seguridad de una vacuna tetravalente contra el dengue (TAK-003) en adolescentes sanos residentes en Ciudad de México, considerada un área no endémica de dengue (NCT03341637). Métodos. Se asignó de manera aleatoria a un grupo de participantes de 12 a 17 años en una proporción 3:1 para que recibieran dos dosis (en el mes 0 y en el mes 3) de la vacuna TAK-003 o de un placebo. Se evaluó la inmunogenicidad mediante un análisis de microneutralización de anticuerpos neutralizantes del virus del dengue al inicio del estudio y en los meses 4 y 9. Se registraron los eventos adversos de notificación solicitada y los referidos por iniciativa propia después de cada vacunación. A lo largo del estudio se registraron los eventos adversos graves y los que requirieron atención médica. Resultados. Participaron 400 adolescentes y 391 (97,8%) finalizaron el estudio. 36 adolescentes (9%) fueron seropositivos a ≥1 serotipos (título recíproco ≥10) al inicio del estudio. La media geométrica de los títulos en las personas seronegativas vacunadas con TAK-003 al inicio del estudio fue de 328, 1743, 120 y 143 en el mes 4 y 135, 741, 46 y 38 en el mes 9 en relación con DENV-1, -2, -3 y -4, respectivamente. La media geométrica de los títulos de las personas que recibieron un placebo se mantuvo en <10. Las tasas de seropositividad tetravalente en los vacunados fueron 99,6% y 85,8% a los meses 4 y 9, respectivamente. Se consideró relacionado con el tratamiento un evento adverso con atención médica que tuvo lugar en cada grupo (TAK-003: eritema en el lugar de la inyección; placebo: faringitis). Conclusiones. TAK-003 fue inmunogénica ante los cuatro serotipos y bien tolerada en los adolescentes sin exposición previa al dengue que vivían en Ciudad de México.

[RESUMO]. Objetivo. Descrever a imunogenicidade e a segurança de uma vacina tetravalente contra dengue (TAK-003) em adolescentes saudáveis residentes da Cidade do México, área considerada não endêmica para dengue (ClinicalTrials.gov: NCT03341637). Métodos. Participantes com idade entre 12 e 17 anos foram randomizados a uma proporção de 3:1 para receber duas doses da vacina TAK-003 ou placebo (no mês 0 e no mês 3). A imunogenicidade foi avaliada pelos títulos de anticorpos neutralizantes contra dengue determinados em ensaio de microneutralização ao início do estudo, no mês 4 e no mês 9. A ocorrência de eventos adversos solicitados ou espontâneos foi registrada após cada rodada de vacinação. Eventos adversos graves e eventos adversos que exigiram atendimento médico foram monitorados ao longo de todo o estudo. Resultados. De 400 adolescentes incluídos na amostra estudada, 391 (97,8%) completaram o estudo. Trinta e seis (9%) apresentaram positividade basal a um ou mais sorotipos virais da dengue (título recíproco ≥10). A média geométrica dos títulos de anticorpos nos vacinados com TAK-003 que eram soronegativos ao início do estudo foi de 328, 1743, 120 e 143 no mês 4 e 135, 741, 46 e 38 no mês 9, contra os sorotipos virais DENV-1, DENV-2, DENV-3 e DENV-4, respectivamente. A média geométrica dos títulos de anticorpos no grupo placebo se manteve abaixo de 10. A taxa de soropositividade tetravalente nos vacinados foi de 99,6% no mês 4 e 85,8% no mês 9. Um único evento adverso que exigiu atendimento médico em cada grupo foi considerado relacionado ao tratamento (eritema no local de aplicação no grupo TAK-003 e faringite no grupo placebo). Conclusão. A vacina TAK-003 demonstrou ser imunogênica contra os quatro sorotipos virais da dengue e foi bem tolerada em adolescentes residentes da Cidade do México sem história pregressa de infecção pela dengue.

Clinical study of hyaluronic acid gel in dyspareunia caused by vaginal dryness / Estudio clínico con un gel de ácido hialurónico en la dispareunia por sequedad vaginal

Objective: Hyaluronic acid plays a key role in the hydration, elasticity, and lubrication of the vagina. We evaluated the efficacy of a hyaluronic acid gel (Hyaluron mucus(R)) in the treatment of dyspareunia due to vaginal dryness. Material and methods: A total of 150 women applied the gel using their fingers before intercourse. The gel could also be applied simultaneously by the partner. We assessed the intensity of pain, discomfort during intercourse, and degree of vaginal dryness; we also recorded overall opinion (physician and/or patient) on the efficacy and tolerability of the gel and on its cosmetic and medical properties. Adverse effects and their causality were also recorded. Results: An improvement in pain, discomfort during intercourse, and vaginal dryness was reported by 91%, 84%, and 92% of patients, respectively. Medical opinion was favorable in 81% of cases and moderate in the remaining 19%. Patient opinion was favorable in 82%, moderate in 15%, and poor in 3%. Tolerability was good (2 cases of pruritus, 3 of stinging, and 1 of burning sensation). Compared with the previous treatment, the new gel was considered better by 64% of the women, equal or similar by 33%, and worse by 4%. Conclusions: The hyaluronic acid gel studied (Hyaluron mucus(R)) significantly improved vaginal dryness and dyspareunia with good tolerability and favorable cosmetic-medical properties in around 90% of cases

Objetivo: el ácido hialurónico es clave en la hidratación, elasticidad y lubricación vaginal. Hemos valorado la eficacia de un gel de ácido hialurónico (Hyaluron mucus(R)) en el tratamiento de la dispareunia asociada a sequedad vaginal. Material y métodos: 150 mujeres se aplicaron el gel en la vagina digitalmente antes de cada relación sexual, y se dejó abierta la posibilidad de que se aplicara simultáneamente por la pareja. Se valoraron la intensidad del dolor, la dificultad en la relación y el grado de sequedad vaginal; se registró la opinión global (del médico y/o del paciente) sobre la eficacia, la tolerabilidad y las características cosmético-galénicas del gel. También se recogieron los efectos adversos y su imputabilidad. Resultados: el dolor, la dificultad en la relación y la sequedad vaginal mejoraron en el 91%, el 84% y el 92%, respectivamente. El juicio médico global fue bueno para el 81% de los casos y moderado en el 19% restante, para las pacientes fue bueno en el 82%, moderado en el 15% y malo en un 3%. La tolerabilidad ha sido buena (2 casos de prurito, 3 de escozor y 1 de quemazón). El gel en estudio fue considerado mejor por el 64% de las mujeres, igual o semejante por el 33% y peor por el 4%, respecto al tratamiento previo. Conclusiones: el gel de ácido hialurónico estudiado mejora de forma relevante en torno al 90% de los casos la sequedad vaginal y la dispareunia con una buena tolerabilidad y aceptabilidad cosmeto-galénica

Frequency of FRAX risk factors in osteopenic postmenopausal women with and without history of fragility fracture.

OBJECTIVE: Fractures associated with bone fragility represent a major public health concern. Although the risk of bone fracture is higher among patients with osteoporosis, the number of fractures is usually higher among patients with osteopenia due to its higher prevalence. METHODS: This is an observational case series study that compares the frequencies of nonskeletal risk factors for osteoporotic fractures in osteopenic postmenopausal women with previous clinical fragility fractures (FFs) and osteopenic postmenopausal women without previous FF. Risk factors included in the FRAX algorithm and other selected risk factors, including asymptomatic vertebral fractures, were evaluated. RESULTS: A total of 735 (50.3% with prior FF and 49.7% without prior FF) postmenopausal women were evaluated (median age, 60 y; mean bone mineral density [BMD] femoral neck T score of -1.67). The frequency of the following risk factors was significantly higher among women with FF-FRAX algorithm: age, use of corticosteroids, and BMD femoral neck T score; other factors: Hispanic ethnicity, falls during the last year, and BMD lumbar T score. In addition, the frequency of previously undetected asymptomatic vertebral fractures was four times higher among women with a history of FF. CONCLUSIONS: The results of the present study support the need to assess the presence of asymptomatic vertebral fractures and BMD T scores in osteopenic postmenopausal women. The risk evaluation of this subpopulation can be accomplished by using some of the risk factors included in the FRAX algorithm combined with other conventional risk factors.