Management of hypertension and dyslipidemia in Mexico: evidence, gaps, and approach / Manejo de la hipertensión y dislipidemia en México: evidencia, brechas y aproximaciones

Abstract Hypertension and dyslipidemia are key risk factors for cardiovascular disorders and mortality worldwide. To understand the local health system challenges faced in the management of the two conditions, a semi-systematic approach was adopted for quantifying stages of the journey of care of adult Mexican patients, namely, awareness, screening, diagnosis, treatment, adherence, and control. A structured literature search was conducted for articles published in English from 2010 to 2019 in EMBASE and MEDLINE databases. The articles restricted to patient subgroups, or not having national representativeness, thesis abstracts, letters to the editor, editorials, or case studies were excluded. In addition, an unstructured unrestricted literature search was conducted, on websites of Incidence and Prevalence Database, World Health Organization, Country's Ministry of Health, and Google. Last search was run on 28 August 2020 for Hypertension and 12 November 2019 for Dyslipidemia. Weighted or simple means were calculated for the pooled data. Seven articles of 647 retrievals for hypertension and 11 articles of 1265 retrievals for dyslipidemia were included in the review. The prevalence of hypertension was estimated to be 24.1%, while 59.9% of patients had awareness, 97.5% underwent screening, 18.4% had diagnosis, 50% received treatment, 50% were adherent to treatment, and 49.9% had disease control. Prevalence of dyslipidemia was estimated as 36.7%, while 8.6% of patients had awareness, 48.1% underwent screening, 28% had diagnosis, 68.9% received treatment, 50% were adherent to treatment, and 30% had disease control. The study suggested that addressing the synergistic effect of hypertension and dyslipidemia could reduce cardiovascular risk associated with these conditions.

Resumen La hipertensión y la dislipidemia -especialmente la hipercolesterolemia- son factores de riesgo cardiovascular que impactan directamente en la prevalencia e incidencia de enfermedades cardiovasculares en todo el mundo y México no es la excepción. Para comprender los desafíos que enfrenta el sistema de salud de nuestro país, especialmente en lo relacionado con el diagnóstico, tratamiento y control de los factores de riesgo cardiovascular mencionados, realizamos un análisis semi-sistemático de la literatura con el objetivo de evaluar las fases del proceso de atención de pacientes adultos mexicanos en lo relacionado con el conocimiento, detección, diagnóstico, tratamiento, adherencia y control de hipertensión y dislipidemia. Se llevó a cabo una investigación bibliográfica semi-sistemática de los artículos publicados en inglés del año 2010 al año 2019; las bases de datos exploradas fueron EMBASE y MEDLINE. Se excluyeron del análisis los artículos sin representatividad nacional, así como los resúmenes de tesis, cartas al editor, editoriales o estudios de casos. Además, se realizó una búsqueda bibliográfica sin restricciones, en los sitios Web de las bases de datos sobre Incidencia y Prevalencia, Organización Mundial de la Salud, Secretaría de Salud de México y Google. La última búsqueda sobre hipertensión se realizó el 28 de agosto del 2020 y sobre dislipidemia el 12 de noviembre del 2019. Se calcularon las medias ponderadas o simples para la recolección de datos. En la revisión, se incluyeron 7 artículos de 647 sobre hipertensión y 11 artículos de 1,265 sobre dislipidemia. Se estimó que la prevalencia de hipertensión en México es de 24.1%; 97.5% de la población reportó haber sido sometida a alguna prueba de detección; 59.9% tuvo conocimiento del diagnóstico; 18.4 % se reconocen con hipertensión; 50% reciben tratamiento; 50% es adherente al mismo, y finalmente solo un 49.9 % tienen control de la hipertensión. Se estimó que la prevalencia de dislipidemia en México es de 36.7%; 48.1% de la población reportó haber sido sometida a alguna prueba de detección; 8.6% tuvo conocimiento del diagnóstico; 28% se conocen con dislipidemia; 68.9% reciben tratamiento; 50% es adherente al mismo, y finalmente solo 30% tuvo control de la dislipidemia. La evidencia revisada hace evidente una gran área de oportunidad para mejorar los índices de diagnóstico, tratamiento y control de estos dos factores sinérgicos para el riesgo de enfermedades cardiovasculares.

Management of hypertension and dyslipidemia in Mexico: Evidence, gaps, and approach.

Hypertension and dyslipidemia are key risk factors for cardiovascular disorders and mortality worldwide. To understand the local health system challenges faced in the management of the two conditions, a semi-systematic approach was adopted for quantifying stages of the journey of care of adult Mexican patients, namely, awareness, screening, diagnosis, treatment, adherence, and control. A structured literature search was conducted for articles published in English from 2010 to 2019 in EMBASE and MEDLINE databases. The articles restricted to patient subgroups, or not having national representativeness, thesis abstracts, letters to the editor, editorials, or case studies were excluded. In addition, an unstructured unrestricted literature search was conducted, on websites of Incidence and Prevalence Database, World Health Organization, Country's Ministry of Health, and Google. Last search was run on 28 August 2020 for Hypertension and 12 November 2019 for Dyslipidemia. Weighted or simple means were calculated for the pooled data. Seven articles of 647 retrievals for hypertension and 11 articles of 1265 retrievals for dyslipidemia were included in the review. The prevalence of hypertension was estimated to be 24.1%, while 59.9% of patients had awareness, 97.5% underwent screening, 18.4% had diagnosis, 50% received treatment, 50% were adherent to treatment, and 49.9% had disease control. Prevalence of dyslipidemia was estimated as 36.7%, while 8.6% of patients had awareness, 48.1% underwent screening, 28% had diagnosis, 68.9% received treatment, 50% were adherent to treatment, and 30% had disease control. The study suggested that addressing the synergistic effect of hypertension and dyslipidemia could reduce cardiovascular risk associated with these conditions.

La hipertensión y la dislipidemia -especialmente la hipercolesterolemia- son factores de riesgo cardiovascular que impactan directamente en la prevalencia e incidencia de enfermedades cardiovasculares en todo el mundo y México no es la excepción. Para comprender los desafíos que enfrenta el sistema de salud de nuestro país, especialmente en lo relacionado con el diagnóstico, tratamiento y control de los factores de riesgo cardiovascular mencionados, realizamos un análisis semi-sistemático de la literatura con el objetivo de evaluar las fases del proceso de atención de pacientes adultos mexicanos en lo relacionado con el conocimiento, detección, diagnóstico, tratamiento, adherencia y control de hipertensión y dislipidemia. Se llevó a cabo una investigación bibliográfica semi-sistemática de los artículos publicados en inglés del año 2010 al año 2019; las bases de datos exploradas fueron EMBASE y MEDLINE. Se excluyeron del análisis los artículos sin representatividad nacional, así como los resúmenes de tesis, cartas al editor, editoriales o estudios de casos. Además, se realizó una búsqueda bibliográfica sin restricciones, en los sitios Web de las bases de datos sobre Incidencia y Prevalencia, Organización Mundial de la Salud, Secretaría de Salud de México y Google. La última búsqueda sobre hipertensión se realizó el 28 de agosto del 2020 y sobre dislipidemia el 12 de noviembre del 2019. Se calcularon las medias ponderadas o simples para la recolección de datos. En la revisión, se incluyeron 7 artículos de 647 sobre hipertensión y 11 artículos de 1,265 sobre dislipidemia. Se estimó que la prevalencia de hipertensión en México es de 24.1%; 97.5% de la población reportó haber sido sometida a alguna prueba de detección; 59.9% tuvo conocimiento del diagnóstico; 18.4 % se reconocen con hipertensión; 50% reciben tratamiento; 50% es adherente al mismo, y finalmente solo un 49.9 % tienen control de la hipertensión. Se estimó que la prevalencia de dislipidemia en México es de 36.7%; 48.1% de la población reportó haber sido sometida a alguna prueba de detección; 8.6% tuvo conocimiento del diagnóstico; 28% se conocen con dislipidemia; 68.9% reciben tratamiento; 50% es adherente al mismo, y finalmente solo 30% tuvo control de la dislipidemia. La evidencia revisada hace evidente una gran área de oportunidad para mejorar los índices de diagnóstico, tratamiento y control de estos dos factores sinérgicos para el riesgo de enfermedades cardiovasculares.

A novel intronic variant in PIGB in Acrofrontofacionasal dysostosis type 1 patients expands the spectrum of phenotypes associated with GPI biosynthesis defects.

Acrofrontofacionasal dysostosis type 1 (AFFND1) is an extremely rare disorder characterized by several dysmorphic features, skeletal abnormalities and intellectual disability, and described only in seven patients in the literature. A biallelic variant in the Neuroblastoma Amplified Sequence (NBAS) gene was recently identified in two Indian patients with AFFND1. Here we report genetic investigation of AFFND1 in the originally described Brazilian families and the identification of an extremely rare, recessively-inherited, intronic variant in the Phosphatidylinositol Glycan class B (PIGB) gene NC_000015.10 (NM_004855.4): c.795-19T > G) in the affected individuals. The PIGB gene encodes an enzyme involved in the biosynthesis of the glycosylphosphatidylinositol (GPI) anchor, which is required for the post-translational modification of a large variety of proteins, enabling their correct cellular localization and function. Recessive variants in PIGB have previously been reported in individuals with a neurodevelopmental syndrome having partial overlap with AFFND1. In vitro assays demonstrated that the intronic variant leads to exon skipping, suggesting the Brazilian AFFND1 patients may be null for PIGB, in agreement with their severe clinical phenotype. These data increase the number of pathogenic variants in the PIGB gene, place AFFND1 among GPI deficiencies and extend the spectrum of phenotypes associated with GPI biosynthesis defects.

Mandibulofacial dysostosis Bauru type: Refining the phenotype.

Mandibulofacial dysostosis (MFD) Bauru type (OMIM 604830) is a rare genetic condition characterized mainly by malar hypoplasia, orofacial cleft, and micrognathia. Here, we describe the clinical and radiographic sings of 13 individuals (12 female and 1 male) from eight unrelated kindreds with MFD Bauru type, including four previously reported cases, treated at the Hospital for Rehabilitation of Craniofacial Anomalies. The clinical phenotype was characterized by severe underdevelopment of mandible, midface hypoplasia, orofacial cleft, bitemporal narrowing, mild upper eyelid down slanting, high nasal bridge, thick and everted lower lip, minor ears abnormalities, and hearing loss. Radiographic aspects included downslanting of zygomatic arch, maxillary hypoplasia, microretrognathia, hypoplastic mandibular condyles, and ectopic external auditory canal. Recurrence was observed in two of eight families and the affected distribution pattern was compatible with autosomal dominant inheritance in one and autosomal recessive in another, indicating possible genetic heterogeneity for this condition. Clinical and radiographic findings in this report contribute to the delineation of this rare MFD.

Targeted molecular investigation in patients within the clinical spectrum of Auriculocondylar syndrome.

Auriculocondylar syndrome, mainly characterized by micrognathia, small mandibular condyle, and question mark ears, is a rare disease segregating in an autosomal dominant pattern in the majority of the families reported in the literature. So far, pathogenic variants in PLCB4, GNAI3, and EDN1 have been associated with this syndrome. It is caused by a developmental abnormality of the first and second pharyngeal arches and it is associated with great inter- and intra-familial clinical variability, with some patients not presenting the typical phenotype of the syndrome. Moreover, only a few patients of each molecular subtype of Auriculocondylar syndrome have been reported and sequenced. Therefore, the spectrum of clinical and genetic variability is still not defined. In order to address these questions, we searched for alterations in PLCB4, GNAI3, and EDN1 in patients with typical Auriculocondylar syndrome (n = 3), Pierre Robin sequence-plus (n = 3), micrognathia with additional craniofacial malformations (n = 4), or non-specific auricular dysplasia (n = 1), which could represent subtypes of Auriculocondylar syndrome. We found novel pathogenic variants in PLCB4 only in two of three index patients with typical Auriculocondylar syndrome. We also performed a detailed comparative analysis of the patients presented in this study with those previously published, which showed that the pattern of auricular abnormality and full cheeks were associated with molecularly characterized individuals with Auriculocondylar syndrome. Finally, our data contribute to a better definition of a set of parameters for clinical classification that may be used as a guidance for geneticists ordering molecular testing for Auriculocondylar syndrome. © 2017 Wiley Periodicals, Inc.

An unusual presentation of oculoauriculovertebral spectrum with a Tessier 30 cleft: report on two cases.

Oculoauriculovertebral spectrum (OAVS, OMIM 164210) is a complex condition characterized by defects in aural, oral, and mandibular development. Other craniofacial and extracranial anomalies can be present. With the exception of the Tessier number 7 cleft, atypical clefting has rarely been reported in association with OAVS. Here, we report on two unrelated cases with a typical phenotype of OAVS and a Tessier 30 associated cleft. One of them also had other atypical facial clefts. We discuss the association between atypical facial clefts and OAVS.

Novel variants in GNAI3 associated with auriculocondylar syndrome strengthen a common dominant negative effect.

Auriculocondylar syndrome is a rare craniofacial disorder comprising core features of micrognathia, condyle dysplasia and question mark ear. Causative variants have been identified in PLCB4, GNAI3 and EDN1, which are predicted to function within the EDN1-EDNRA pathway during early pharyngeal arch patterning. To date, two GNAI3 variants in three families have been reported. Here we report three novel GNAI3 variants, one segregating with affected members in a family previously linked to 1p21.1-q23.3 and two de novo variants in simplex cases. Two variants occur in known functional motifs, the G1 and G4 boxes, and the third variant is one amino acid outside of the G1 box. Structural modeling shows that all five altered GNAI3 residues identified to date cluster in a region involved in GDP/GTP binding. We hypothesize that all GNAI3 variants lead to dominant negative effects.

Development of a strategic plan by the Mozambican Association of Obstetricians and Gynaecologists: direct and indirect effects.

The Mozambican Association of Obstetricians and Gynaecologists (AMOG) received support from the FIGO Leadership in Obstetrics and Gynecology for Impact and Change (LOGIC) Initiative in Maternal and Newborn Health (MNH) to strengthen its organizational capacity and to assume leadership in MNH through the development of a strategic plan. The planning process involved identification of key stakeholders; analysis of strengths and weaknesses; stakeholder consultation; consultation with AMOG members; and ratification at the annual general meeting. The participatory process led to the development of vision and mission statements. Furthermore, core values and strategic goals were identified: (1) to contribute to the implementation of governmental plans for improving MNH; (2) to assume leadership in advancing the practice of obstetrics and gynecology through education and training; and (3) to continue to strengthen organizational capacity. Consequently, relationships among members were reinforced and the visibility and recognition of AMOG as a key stakeholder in MNH increased.

A noncoding expansion in EIF4A3 causes Richieri-Costa-Pereira syndrome, a craniofacial disorder associated with limb defects.

Richieri-Costa-Pereira syndrome is an autosomal-recessive acrofacial dysostosis characterized by mandibular median cleft associated with other craniofacial anomalies and severe limb defects. Learning and language disabilities are also prevalent. We mapped the mutated gene to a 122 kb region at 17q25.3 through identity-by-descent analysis in 17 genealogies. Sequencing strategies identified an expansion of a region with several repeats of 18- or 20-nucleotide motifs in the 5' untranslated region (5' UTR) of EIF4A3, which contained from 14 to 16 repeats in the affected individuals and from 3 to 12 repeats in 520 healthy individuals. A missense substitution of a highly conserved residue likely to affect the interaction of eIF4AIII with the UPF3B subunit of the exon junction complex in trans with an expanded allele was found in an unrelated individual with an atypical presentation, thus expanding mutational mechanisms and phenotypic diversity of RCPS. EIF4A3 transcript abundance was reduced in both white blood cells and mesenchymal cells of RCPS-affected individuals as compared to controls. Notably, targeting the orthologous eif4a3 in zebrafish led to underdevelopment of several craniofacial cartilage and bone structures, in agreement with the craniofacial alterations seen in RCPS. Our data thus suggest that RCPS is caused by mutations in EIF4A3 and show that EIF4A3, a gene involved in RNA metabolism, plays a role in mandible, laryngeal, and limb morphogenesis.

Respiratory function in children of asthmatic mothers.

OBJECTIVE: To evaluate lung function and clinical manifestations suggestive of asthma in children of mothers with a reported medical diagnosis of asthma. METHODS: An observational cross-sectional analytical study nested in a cohort of 4,757 pregnant women. A total of 86 six-year-old children were evaluated, born to mothers with a medical diagnosis of asthma before pregnancy. Information was collected regarding clinical symptoms of atopy and respiratory diseases, as well as socioeconomic and exposure variables; the children were submitted to spirometry. RESULTS: Spirometric alterations were observed in 30.3% of cases, with a prevalence of asthma in those who had an obstructive pattern. 9.3% of the children had a previous medical diagnosis of asthma; however, the established diagnosis based on the presence and frequency of asthma symptoms was 18.6%. Of the 86 participating children, 37.2% had a score of five or more points in the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, which was associated with spirometry alterations (p=0.002). After multiple logistic regression analysis, higher paternal education, higher number of bedrooms in the family's home, and mother who did not have "wheezing" episodes during pregnancy were statistically significant as protective factors for the presence of respiratory disorder detected by spirometry. CONCLUSIONS: The frequency of spirometry alterations in children of asthmatic mothers was high; the restrictive pattern was more often observed that the obstructive. There was a higher incidence of obstructive test results in those who presented clinical symptoms of asthma, with a higher frequency of clinical diagnosis of asthma than that found in the literature.

Função respiratória em filhos de mães asmáticas / Respiratory function in children of asthmatic mothers

OBJETIVO: Avaliar a função pulmonar e as manifestações clínicas sugestivas de asma em filhos de mães com diagnóstico médico referido de asma. MÉTODOS: Estudo observacional transversal analítico aninhado a uma coorte de 4.757 parturientes. Foram avaliadas 86 crianças aos seis anos de idade, filhas de mães com diagnóstico médico de asma antes da gestação. Foram coletadas informações referentes a sintomatologias clínicas de atopias e doenças respiratórias, variáveis socioeconômicas e de exposição; tendo sido as crianças submetidas à espirometria. RESULTADOS: Foram encontrados 30,3% de alterações espirométricas, havendo predomínio do diagnóstico de asma nos que apresentaram padrão obstrutivo. Diagnóstico médico pregresso de asma ocorreu em 9,3% das crianças; contudo, o diagnóstico estabelecido a partir da presença e frequência dos sintomas de asma representou 18,6%. Das 86 crianças participantes, 37,2% tiveram um escore de cinco ou mais pontos no questionário ISAAC, estando isso associado à alteração do padrão espirométrico (p = 0,002). Após a regressão logística múltipla, maior escolaridade paterna, maior número de quartos no domicílio e o fato de a mãe não ter apresentado "chiado" durante a gestação foram estatisticamente significantes como fatores protetores para a presença de distúrbio ventilatório à espirometria. CONCLUSÕES: A frequência de alterações do teste espirométrico em filhos de mães asmáticas foi alta, com o padrão restritivo ocorrendo mais vezes que o obstrutivo. Houve uma maior ocorrência de exames obstrutivos naqueles que apresentavam sintomatologia clínica de asma, com uma frequência de diagnóstico clínico de asma superior à encontrada na literatura.

OBJECTIVE: To evaluate lung function and clinical manifestations suggestive of asthma in children of mothers with a reported medical diagnosis of asthma. METHODS: An observational cross-sectional analytical study nested in a cohort of 4,757 pregnant women. A total of 86 six-year-old children were evaluated, born to mothers with a medical diagnosis of asthma before pregnancy. Information was collected regarding clinical symptoms of atopy and respiratory diseases, as well as socioeconomic and exposure variables; the children were submitted to spirometry. RESULTS: Spirometric alterations were observed in 30.3% of cases, with a prevalence of asthma in those who had an obstructive pattern. 9.3% of the children had a previous medical diagnosis of asthma; however, the established diagnosis based on the presence and frequency of asthma symptoms was 18.6%. Of the 86 participating children, 37.2% had a score of five or more points in the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, which was associated with spirometry alterations (p = 0.002). After multiple logistic regression analysis, higher paternal education, higher number of bedrooms in the family's home, and mother who did not have "wheezing" episodes during pregnancy were statistically significant as protective factors for the presence of respiratory disorder detected by spirometry. CONCLUSIONS: The frequency of spirometry alterations in children of asthmatic mothers was high; the restrictive pattern was more often observed that the obstructive. There was a higher incidence of obstructive test results in those who presented clinical symptoms of asthma, with a higher frequency of clinical diagnosis of asthma than that found in the literature.

Clinical findings in children with congenital anomalies and misoprostol intrauterine exposure: a study of 38 cases.

The authors describe the clinical findings of 38 children with congenital anomalies and misoprostol intrauterine exposure. This study included 38 cases, ascertained from case series of the Hospital of Rehabilitation of Craniofacial Anomalies from University of São Paulo, with evidence of intrauterine exposure to misoprostol in the first trimester of the pregnancy. Information about misoprostol intake and drug administration route was obtained through interviews with mothers. Clinical evaluation showed 18 individuals with facial phenotype compatible with Moebius syndrome; 11 individuals with multiple congenital anomalies; and nine individuals with nonsyndromic cleft lip and/or cleft palate. This study showed a widening of the phenotypic spectrum associated with misoprostol embryotoxicity.

Regulação-organização do Setor de Regulação nas Unidades Básicas de Saúde da Supervisão Técnica de Saúde Sto. Amaro / Cidade Ademar - CRSSul

A Supervisão Técnica de Saúde Santo Amaro e Cidade Ademar (STS SACA) possui em sua área de abrangência 42 Unidades de Saúde, das quais 33 mantém setor de Regulação que abrange conjunto de relações, tecnologias e ações que viabilizem o acesso dos usuários às consultas especializadas e aos serviços de apoio diagnóstico, de forma oportuna e organizada, buscando atender às suas necessidades. O setor de Regulação de cada Unidade Básica de Saúde (UBS) visa garantir resolubilidade do atendimento à demanda, através dos recursos disponíveis na rede pública, que compreende unidades ambulatórias próprias, municipalizadas e estaduais e estabelecimentos particulares conveniados. Para desempenho satisfatório são necessários recursos humanos e materiais mínimos, tais como funcionário exclusivo, computadores com acesso a internet, impressora e telefone próprio

Regulação-organização do Setor de Regulação nas Unidades Básicas de Saúde da Supervisão Técnica de Saúde Sto. Amaro / Cidade Ademar - CRSSul / Regulation-organization Sector Basic Health Units in the Health Technical Supervision Sto. Amaro / Cidade Ademar - CRSSul

A Supervisão Técnica de Saúde Santo Amaro e Cidade Ademar (STS SACA) possui em sua área de abrangência 42 Unidades de Saúde, das quais 33 mantém setor de Regulação que abrange conjunto de relações, tecnologias e ações que viabilizem o acesso dos usuários às consultas especializadas e aos serviços de apoio diagnóstico, de forma oportuna e organizada, buscando atender às suas necessidades. O setor de Regulação de cada Unidade Básica de Saúde (UBS) visa garantir resolubilidade do atendimento à demanda, através dos recursos disponíveis na rede pública, que compreende unidades ambulatórias próprias, municipalizadas e estaduais e estabelecimentos particulares conveniados. Para desempenho satisfatório são necessários recursos humanos e materiais mínimos, tais como funcionário exclusivo, computadores com acesso a internet, impressora e telefone próprio(AU

Ruthenium-Catalyzed Oppenauer-Type Oxidation of 3beta-Hydroxy Steroids. A Highly Efficient Entry into the Steroidal Hormones with 4-En-3-one Functionality.

Oxidation of 5-unsaturated 3beta-hydroxy steroids 1 to the corresponding 4-en-3-one derivatives 2 can be performed efficiently by acetone at reflux in the presence of a catalytic system consisting of either (PPh(3))(3)RuCl(2) (3) and K(2)CO(3) or [(C(4)Ph(4)COHOCC(4)Ph(4))(&mgr;-H)][(CO)(4)Ru(2)] (4). The reaction proceeds via a ruthenium-catalyzed dehydrogenation of 1 and subsequent hydrogen transfer to acetone with concomitant double bond migration.