Tiered Pricing and Alternative Mechanisms for Equitative Access to Vaccines in Latin America: A Narrative Review of the Literature.

OBJECTIVES: To review and describe alternative strategies for the supply of vaccines in Latin America. METHODS: We conducted a narrative review to explore and describe alternatives for equitable vaccine access in Latin America. We searched and considered the main access strategies reported in the literature through PubMed, Science Direct, and Google Scholar. Additionally, we reviewed the web sites of key stakeholders. The search was conducted using the following keywords: ("access" or "availability" or "acquisition" or "affordability" or "tiered pricing") and ("vaccine"). Subsequently, documents that met the inclusion criteria were selected. Finally, findings were grouped by means of a thematic analysis and an interpretative synthesis. RESULTS: Twenty-four publications were included. We identified 5 main topics: current supply strategies, challenges for the acquisition of vaccines, vaccine prices equity, alternative supply strategies, and the advantages and impact of a tiered pricing strategy. CONCLUSIONS: Our review suggests that tiered pricing can be an tool for accelerating the process of introducing vaccines in low-income countries at affordable prices and for countries that do not adhere to the current procurement mechanisms or are not eligible for Vaccine Alliance because giving countries prices for vaccines that reflect their ability to pay can result in better programmatic and financial planning for the purchase of these vaccines, and in return, vaccine manufacturers can gain access to wider markets However, this model has not been z improve access to vaccines that are aimed only at developing countries, mainly because the market in these countries is not profitable for producers.

Capacidad cardiorrespiratoria en pacientes con fibromialgia: revisión sistemática y metaanálisis / Cardiorespiratory fitness in patients with fibromyalgia: a systematic review with meta-analysis

Introducción. La fibromialgia es una enfermedad crónica caracterizada por dolor musculoesquelético generalizado que puede producir deterioro en la capacidad cardiorrespiratoria; sin embargo, hasta la fecha no está claro cuál es el compromiso cardiorrespiratorio en los pacientes con esta condición. Objetivos. Determinar la capacidad cardiorrespiratoria de los pacientes con fibromialgia y analizar las diferencias con controles sanos. Métodos. Se realizó una búsqueda sistemática en las bases de datos PubMed, Web of Science, ScienceDirect, Redalyc, Scopus, Lilacs y Google Scholar. Se incluyeron estudios observacionales publicados en inglés, español y portugués que evaluaran la capacidad cardiorrespiratoria en pacientes con fibromialgia en comparación con sujetos sanos. La calidad metodológica se evaluó mediante la escala Newcastle-Ottawa. Bajo un modelo de efectos aleatorios, el tamaño del efecto combinado se calculó con la diferencia de medias estandarizadas y su intervalo de confianza del 95%; la heterogeneidad se analizó mediante la prueba I-cuadrado (I2). Se realizó análisis de subgrupos para evaluar la influenciadel tipo de prueba de ejercicio clínica utilizada. Resultados. Se incluyeron 14 estudios, con un total de 1.623 participantes (todos de sexo femenino), que cumplieron los criterios de inclusión. Se encontró una diferencia significativa en la distancia recorrida en la prueba de la caminata de seis minutos en mujeres con fibromialgia en comparación con mujeres sanas. Los estudios con ergoespirometría presentaron resultados no concluyentes. Conclusiones. Los pacientes con fibromialgia presentan una menor capacidad cardiorrespiratoria en la prueba de la caminata de seis minutos en comparación con los controles sanos. En este sentido, se necesitan investigaciones que permitan establecer métodos adecuados de medición de la aptitud cardiorrespiratoria que tengan en cuenta las condiciones particulares de los pacientes con esta enfermedad.

Introduction. Fibromyalgia is a chronic disease characterized by widespread musculoskeletal pain that can lead to deterioration in cardiorespiratory capacity; however, to date it is not clear what the cardiorespiratory compromise is in patients with this condition. Objectives. To determine the cardiorespiratory capacity of patients with fibromyalgia and analyze the differences with healthy controls. Methods: A systematic search was performed in PubMed, Web of Science, ScienceDirect, Redalyc, Scopus, Lilacs and Google Scholar databases. Observational studies published in English, Spanish and Portuguese that assessed the car-diorespiratory capacity in patients with fibromyalgia compared with healthy subjects were included. The methodolog-ical quality was assessed using the Newcastle-Ottawa scale. Under a random-effects model, the pooled effect size was calculated with the standardized mean difference and its 95% confidence interval; heterogeneity was analyzed using the I-square (I2) test. Subgroup analyses were performed to assess the influence of the type of clinical exercise testing used. Results. 14 studies, with a total of 1623 participants (all women), that met the inclusion criteria were included. A sig-nificant difference in distance covered on the six-minute walk test was found in women with fibromyalgia compared with healthy women. the studies with ergospirometry showed inconclusive results. Conclusions. Patients with fibromyalgia have lower cardiorespiratory capacity on the six-minute walk test compared to healthy controls. In this sense, research is needed to establish adequate methods of measuring cardiorespiratory fitness that take into account the particular conditions of the patients with this disease.

Vinylcyclopropane [3+2] Cycloaddition with Acetylenic Sulfones Based on Visible Light Photocatalysis.

The first intermolecular visible light [3+2] cycloaddition reaction performed on a meta photocycloadduct employing acetylenic sulfones is described. The developed methodology exploits the advantages of combining UV and visible-light in a two-step sequence that provides a photogenerated cyclopropane which, through a strain-release process, generates a new cyclopentane ring while significantly increasing the molecular complexity. Mechanistic studies and DFT calculations indicate an energy transfer pathway for the visible light-driven reaction step. This strategy could be extended to simpler vinylcyclopropanes.

Strain Release Chemistry of Photogenerated Small-Ring Intermediates.

Photochemical processes, such as isomerizations and cycloadditions, have proven to be very useful in the construction of highly strained molecular frameworks. Photoinduced ring strain enables subsequent exergonic reactions which do not require the input of additional chemical energy and provides a variety of attractive synthetic options leading to complex structures. This review covers the progress achieved in the application of sequences combining excitation by ultraviolet light to form strained intermediates, which are further transformed to lower energy products in strain-release reactions. As ring strain is considerable in small ring systems, photogenerated three- and four-membered rings will be covered, mainly focusing on examples from 2000 to May 2020.

Long-term Immunogenicity and Safety of the AS04-adjuvanted Human Papillomavirus-16/18 Vaccine in Four- to Six-year-old Girls: Three-year Follow-up of a Randomized Phase III Trial.

BACKGROUND: The burden of human papillomavirus (HPV) diseases is high in Latin America. HPV vaccines licensed from 2006 onwards offer protection against most HPV-related cancers, especially when introduced into national immunization programs. Barriers to optimal vaccine uptake are, however, lowering the impact of adolescent HPV vaccination programs. Immunization of children might overcome these barriers and be a strategy of choice for some countries. METHODS: This multicenter phase III randomized, controlled, single-blind study (NCT01627561) was conducted in Colombia, Mexico and Panama to assess safety and immunogenicity of 2-dose vaccination with AS04-adjuvanted HPV-16/18 vaccine in girls 4-6 years of age. We report safety outcomes and anti-HPV-16/18 antibody titers measured by enzyme-linked immunosorbent assay in HPV-vaccinated girls that were followed over a 36-month period. RESULTS: Over 36 months (ie, 30 months after the second vaccine dose), among 74 girls included in the HPV group, 1 serious adverse event unrelated to vaccination has been reported. No withdrawal because of (serious) adverse events has been reported. At month 36, all girls in the per-protocol-cohort were still seropositive for anti-HPV-16 and anti-HPV-18 with geometric mean concentrations of 1680.6 and 536.4 enzyme-linked immunosorbent assay units/mL, respectively. CONCLUSIONS: The AS04-adjuvanted HPV-16/18 vaccine administered according to a 2-dose schedule to girls 4-6 years of age induced a high and sustained immunologic response with an acceptable safety profile during the 30 months following vaccination.

Visible Light-Induced Sulfonylation/Arylation of Styrenes in a Double Radical Three-Component Photoredox Reaction.

Simultaneous sulfonylation/arylation of styrene derivatives is achieved in a photoredox-catalyzed three-component reaction using visible light. A broad variety of difunctionalized products is accessible in mostly excellent yields and high diastereoselectivity. The developed reaction is scalable and suitable for the modification of styrene-functionalized biomolecules. Mechanistic investigations suggest the transformation to be operating through a designed sequence of radical formation and radical combination.

Safety and Immunogenicity of the HPV-16/18 AS04-adjuvanted Vaccine in 4-6-year-old Girls: Results to Month 12 From a Randomized Trial.

BACKGROUND: The burden of cervical cancer caused by human papillomavirus (HPV) is high in Latin America. The suboptimal HPV vaccination coverage in adolescents could be improved by pediatric immunization. HPV vaccination has not yet been reported in girls <9 years of age. METHODS: This ongoing phase III, controlled, randomized, single-blind, multicenter study conducted in Colombia, Mexico and Panama (NCT01627561) evaluated the safety and immunogenicity of AS04-HPV-16/18 vaccine in 4-6-year-old girls. Healthy girls (randomized 1:1) received either 2 doses of AS04-HPV-16/18 vaccine (HPV group, N=74) or 1 dose of each measles-mumps-rubella and diphtheria-tetanus-acellular-pertussis vaccines (control group, N=74) 6 months apart. We report the safety and serum anti-HPV-16 and anti-HPV-18 antibodies (measured by enzyme-linked immunosorbent assay) up to 6 months postvaccination, that is, month (M) 12. RESULTS: Injection site pain was the most frequently reported solicited local symptom in HPV vaccinees. The incidence of other solicited and unsolicited symptoms after each vaccination was similar between the HPV and control group. Until M12, 1 girl in the HPV group and 2 in the control group reported serious adverse events; all serious adverse events were assessed as unrelated to study vaccines. No potential immune-mediated diseases were identified. All girls seroconverted for both antigens after 2 doses of AS04-HPV-16/18. In initially seronegative girls, anti-HPV-16 geometric mean concentrations were 20080.0 enzyme-linked immunosorbent assay units (EU)/mL at M7 and 3246.5 EU/mL at M12; anti-HPV-18 geometric mean concentrations were 10621.8 EU/mL at M7 and 1216.6 EU/mL at M12. CONCLUSIONS: Two-dose vaccination with AS04-HPV-16/18 was well tolerated and induced adequate antibody responses in 4-6-year-old girls.

Unexpected ring-closure products derived from 3-(2-allylanilino)-3-phenylacrylate esters: crystal and molecular structures of 3-acetyl-8-allyl-6-methyl-2-phenylquinolin-4-yl acetate and (2RS)-2,8-dimethyl-4-phenyl-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinolin-6-one.

The reactions of two 3-(2-allylanilino)-3-phenylacrylate esters with acetic anhydride and with strong acids has revealed a richly diverse reactivity providing a number of unexpected products. Thus, acetylation of ethyl 3-(2-allylanilino)-3-phenylacrylate, (Ia), or ethyl 3-(2-allyl-4-methylanilino)-3-phenylacrylate, (Ib), with acetic anhydride yields not only the expected acetylated esters, (II), as the major products but also the unexpected polysubstituted quinolines 3-acetyl-8-allyl-2-phenylquinolin-4-yl acetate, (IIIa), and 3-acetyl-8-allyl-6-methyl-2-phenylquinolin-4-yl acetate, (IIIb), as minor products. Subsequent reaction of the major product ethyl 2-[(2-allyl-4-methylanilino)(phenyl)methylidene]-3-oxobutanoate, (IIb), with concentrated sulfuric acid did not provide the expected 3-acetylquinoline derivative, but instead two unexpected products, namely ethyl 4-ethyl-2-phenyl-1,4-dihydroquinoline-3-carboxylate, (IV), and ethyl 3-acetyl-4-ethyl-2-phenyl-3,4-dihydroquinoline-3-carboxylate, (V), in yields of 39 and 22%, respectively. The reaction of (Ib) with Eaton's reagent gave both the quinoline (Z)-6-methyl-2-phenyl-8-(prop-1-en-1-yl)quinolin-4(1H)-one, (VI), and the unexpected tricyclic product (2RS)-2,8-dimethyl-4-phenyl-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinolin-6-one, (VII), in yields of 71 and 12%, respectively. The products (II)-(VII) have all been fully characterized spectroscopically and the crystal structures of two of the unexpected products, i.e. (IIIb) (C23H21NO3) and (VII) (C19H17NO), are reported here. The formation of compounds (IV), (V) and (VII) all require an isomerization of the initial allyl substituent, with migration of the C=C double bond from the terminal site to the internal site. In (IIIb), the two acetyl substituents are oriented such that the intramolecular distance between the two carbonyl O atoms is only 3.243 (2) Å, and in (VII), the five-membered ring adopts a twisted half-chair conformation. The molecules of compound (IIIb) are linked by two independent hydrogen bonds to form sheets built from R4(3)(20) rings and the sheets are linked by a π-π stacking interaction to form a three-dimensional framework structure. The molecules of compound (VII) are linked by a single type of C-H...O hydrogen bond to form centrosymmetric R2(2)(14) dimers. The molecules of compound (V), which crystallizes with Z' = 2, are linked by two N-H...O and two C-H...O hydrogen bonds, forming a chain of rings.

Pielonefritis xantogranulomatosa asociada a flora polimicrobiana / Xantothogranulomatous pyelonephritis associated with polymicrobian flora

La pielonefritis xantogranulomatosa (PX) es una rara infección crónica y severa del parénquima renal. Debido a que sus manifestaciones simulan una neoplasia, el diagnóstico preoperatorio es dificultoso. Habitualmente se asocia a infección bacteriana monomicrobiana. Nosotros comunicamos el caso de PX asociada a infección polimicrobiana, una de las cuales es un microorganismo anaeróbico