Construction and validation of self-care educational technology for caregivers.

OBJECTIVES: to build and validate educational self-care technology for informal caregivers. METHODS: methodological study, anchored in the Delphi technique, carried out in a municipality in the state of Paraná, Brazil, between September 2018 and November 2019. It was developed in three stages: situational diagnosis; elaboration of educational technology; content and appearance validation by expert judges and informal caregivers, using the content validity index and coefficient of variation. RESULTS: after the steps of the methodological process, an educational technology called "Taking Care of Those Who Care" was produced, as an information tool that deals with the self-care of informal caregivers, receiving a content validity index above 0.86 and a variation coefficient. below 20% on all items. CONCLUSIONS: the educational technology was built and evaluated with satisfactory rates by the specialists and target audience, showing a high correlation of agreement, characterizing it as adequate and informative to informal caregivers.

Recreating the Follicular Environment: A Customized Approach for In Vitro Culture of Bovine Oocytes Based on the Origin and Differentiation State.

The mammalian ovary is a large source of oocytes organized into follicles at various stages of folliculogenesis. However, only a limited number of them can be used for in vitro embryo production (IVEP), while most have yet to complete growth and development to attain full meiotic and embryonic developmental competence. While the in vitro growth of primordial follicles in the ovarian cortex has the potential to produce mature oocytes, it is still at an experimental stage. The population of early antral follicles (EAFs), instead, may represent a reserve of oocytes close to completing the growth phase, which might be more easily exploited in vitro and could increase the number of female gametes dedicated to IVEP.Here we present in vitro culture strategies that have been developed utilizing physiological parameters to support the specific needs of oocytes at distinct stages of differentiation, in order to expand the source of female gametes for IVEP by maximizing the attainment of fertilizable oocytes. Furthermore, these culture systems provide powerful tools to dissect the molecular processes that direct the final differentiation of the mammalian oocyte.

Physiological parameters related to oocyte nuclear differentiation for the improvement of IVM/IVF outcomes in women and cattle.

In vitro maturation (IVM) has been applied in numerous different contexts and strategies in humans and animals, but in both cases it represents a challenge still far from being overcome. Despite the large dataset produced over the last two decades on the mechanisms that govern antral follicular development and oocyte metabolism and differentiation, IVM outcomes are still unsatisfactory. This review specifically focuses on data concerning the potential consequences of using supraphysiological levels of FSH during IVM, as well as on the regulation of oocyte chromatin dynamics and its utility as a potential marker of oocyte developmental competence. Taken together, the data revisited herein indicate that a significant improvement in IVM efficacy may be provided by the integration of pre-OPU patient-specific protocols preparing the oocyte population for IVM and more physiological culture systems mimicking more precisely the follicular environment that would be experienced by the recovered oocytes until completion of metaphase II.

Construction and validation of self-care educational technology for caregivers / Construcción y validez de tecnología educacional de autocuidado para cuidadores / Construção e validação de tecnologia educacional de autocuidado para cuidadores informais

ABSTRACT Objectives: to build and validate educational self-care technology for informal caregivers. Methods: methodological study, anchored in the Delphi technique, carried out in a municipality in the state of Paraná, Brazil, between September 2018 and November 2019. It was developed in three stages: situational diagnosis; elaboration of educational technology; content and appearance validation by expert judges and informal caregivers, using the content validity index and coefficient of variation. Results: after the steps of the methodological process, an educational technology called "Taking Care of Those Who Care" was produced, as an information tool that deals with the self-care of informal caregivers, receiving a content validity index above 0.86 and a variation coefficient. below 20% on all items. Conclusions: the educational technology was built and evaluated with satisfactory rates by the specialists and target audience, showing a high correlation of agreement, characterizing it as adequate and informative to informal caregivers.

RESUMEN Objetivos: construir y validar una tecnología educacional de autocuidado para cuidadores informales. Métodos: estudio metodológico, ancorado en la técnica Delphi, realizado en un municipio de Paraná, Brasil, entre septiembre de 2018 a noviembre de 2019. Desarrolló en tres etapas: diagnostico situacional; elaboración de la tecnología educacional; validez de contenido y apariencia por jueces especialistas y por cuidadores informales, por medio del índice de validez de contenido y coeficiente de variación. Resultados: después de las etapas del proceso metodológico, produjo una tecnología educacional denominada "Cuidando de Quien Cuida", como instrumento informativo que versa sobre el autocuidado de cuidadores informales, recibiendo evaluación del índice de validez de contenido arriba de 0,86 y coeficiente de variación debajo de 20% en todos ítems. Conclusiones: la tecnología educacional fue construida y evaluada con índices satisfactorios por los especialistas y público objetivo, presentando alta correlación de concordancia, la caracterizando como adecuada e informativa a cuidadores informales.

RESUMO Objetivos: construir e validar uma tecnologia educacional de autocuidado para cuidadores informais. Métodos: estudo metodológico, ancorado na técnica Delphi, realizado em um município do estado do Paraná, Brasil, entre setembro de 2018 a novembro de 2019. Desenvolveu-se em três etapas: diagnóstico situacional; elaboração da tecnologia educacional; validação de conteúdo e aparência por juízes especialistas e por cuidadores informais, por meio do índice de validade de conteúdo e coeficiente de variação. Resultados: após as etapas do processo metodológico, produziu-se uma tecnologia educacional denominada "Cuidando de Quem Cuida", como instrumento informativo que versa sobre o autocuidado de cuidadores informais, recebendo avaliação do índice de validade de conteúdo acima de 0,86 e coeficiente de variação abaixo de 20% em todos itens. Conclusões: a tecnologia educacional foi construída e avaliada com índices satisfatórios pelos especialistas e público-alvo, apresentando alta correlação de concordância, caracterizando-a como adequada e informativa a cuidadores informais.

Acessibilidade ao diagnóstico de hipertensão arterial na atenção primária à saúde / Accessibility for the diagnosis of hypertension in primary health care / Accesibilidad al diagnóstico de la hipertensión en la atención primaria a la salud

Objetivo: Analisar a acessibilidade ao diagnóstico da hipertensão arterial na Atenção Primária à Saúde. Método: estudo transversal, realizado com 417 pessoas, residentes em um município localizado no noroeste do estado do Paraná. A coleta de dados ocorreu entre fevereiro a junho de 2016,por meio de um instrumento adaptado e validado para avaliação dos serviços ofertados a pessoas com hipertensão arterial na Atenção Primária à Saúde. Na análise dos dados, aplicou-se estatística descritiva e inferencial. Resultados: constatou-se insatisfação quanto tempo gasto para deslocar-se até os serviços de saúde, necessidade de procurar atendimento por mais de três vezes para receber o diagnóstico, tempo de espera superior a 60 minutos para ser atendido e atraso ou perda de dia de trabalho. Conclusão:tais achados refletem a importância de reorganizar a gestão e o planejamento de ações de saúde, com vistas a tornar os serviços de saúde pública mais equânime, resolutivo e longitudinal

Objective:To analyze the accessibility to the diagnosis of hypertension in Primary Health Care. Method: cross-sectional study with 417 people living in a municipality located in the northwest of Paraná state. Data collection took place between February and June 2016, through an adapted and validated instrument to evaluate the services offered to people with hypertension in Primary Health Care. In the data analysis, descriptive and inferential statistics were applied. Results: we found dissatisfaction with the time spent traveling to health services, the need to seek care more than three times to receive the diagnosis, the waiting time over 60 minutes to be attended by and the delay or loss of work day. Conclusion: these findings reflect the importance of reorganizing the management and planning of health actions, with a view to making public health services more equitable, resolute and longitudinal

Objetivo: Analizar la accesibilidad al diagnóstico de hipertensión en Atención Primaria de Salud Método: estudio transversal con 417 personas que viven en un municipio ubicado en el noroeste del estado de Paraná. La recolección de datos se realizó entre febrero y junio de 2016, a través de un instrumento adaptado y validado para evaluar los servicios ofrecidos a las personas con hipertensión en Atención Primaria de Salud. En el análisis de datos, se aplicaron estadísticas descriptivas e inferenciales. Resultados: encontramos insatisfacción con el tiempo dedicado a viajar a los servicios de salud, necesitamos buscar atención más de tres veces para recibir el diagnóstico, tiempo de espera de más de 60 minutos para ser atendido y retraso o pérdida del día. Yo trabajo Conclusión: estos hallazgos reflejan la importancia de reorganizar la gestión y planificación de las acciones de salud, con miras a hacer que los servicios de salud pública sean más equitativas, resueltos y longitudinales

Funcionalização do polietilenoglicol metil éter via reação de bromoacetilação: ativação, caracterização por MALDI-TOF e mecanismo de reação / Poly(ethylene glycol) methyl ether functionalization by bromoacetylation reaction: Activation, characterization by MALDI-TOF and reaction mechanism / Funcionalización de polietilenglicol metil éter mediante reacción de bromoacetilación: activación, caracterización por MALDI-TOF y mecanismo de reacción

Resumo A PEGuilação, reação química de conjugação com a molécula de polietilenoglicol (PEG) ou polietilenoglicol metil éter (mPEG), tem sido amplamente aplicada pelas indústrias farmacêuticas como estratégia de melhoria das propriedades farmaco-cinéticas de compostos bioativos. O PEG é um polímero que possui um esqueleto de poliéter quimicamente inerte e que apresenta grupos hidroxilas (-OH) em suas extremidades. Assim, o PEG para tornar-se apto como reagente de conjugação deve ser ativado com um grupo funcional que seja reativo. Nesse sentido, a bromoaceti-lação apresenta-se como uma alternativa para a funcionalização do PEG. Portanto, nesse trabalho objetivamos descrever em detalhes os procedimentos e o mecanismo de reação envolvida na funcionalização do mPEG, através da reação de bromoacetilação. Além do mais, estudamos a aplicação do MALDI-ToF para a caracterização do produto ativado. Após a bromoacetilação, por um procedimento adaptado, obteve-se o bromoacetil-mPEG-éster, com rendimento bruto de 56,78%. Análises posteriores, por espectrometria de massas por MALDI-ToF, possibilitaram identificar e caracterizar o produto bromoacetilado. Entre as condições de reação, o controle de temperatura (-10 °C a 0 °C) mostrou-se eficaz favorecendo a adição nucleofílica essencial à bromoacetilação. Assim, concluímos que o controle da baixa temperatura reacional é um fator chave para o favorecimento da adição nucleofílica à carbonila e, portanto, essencial na obtenção do mPEG funcionalizado via bromoacetilação. Estudos posteriores serão necessários, no entanto, para confirmar se o mPEG esterificado, nessas condições, poderá ser utilizado na conjugação com moléculas de natureza proteica ou peptídica, por meio de substituição nucleofílica bimolecular.

SUMMARY PEGylation, a chemical reaction of conjugation with the polyethylene glycol molecule (PEG), has been widely applied by the pharmaceutical industries as a strategy to improve the pharmacokinetic properties of bioactive compounds. PEG is a polymer that has a chemically inert polyether backbone and hydroxyl groups (-OH) at its ends. Thus, PEG to become fit as a reagent for conjugation must be activated with a functional group that is reactive. In this sense, bromoacetylation presents itself as an alternative for the functionalization of PEG. Therefore, in this study we aim to describe in detail the procedures and reaction mechanism involved in the functionalization of mPEG through the bromoacetylation reaction. In addition, we used the spectrometric technique, by MALDI-ToF, for the characterization of the activated product. After applying an adapted bromoacetylation procedure, bromoacetyl-mPEG-ester was obtained with a yield of 56.78%. Subsequent analyzes of MALDI-ToF mass spectrometry were able to correctly identify and characterize the bromoacety-lated product. Among the reaction conditions, temperature control (from -10 °C to 0 °C) was effective in favoring the essential nucleophilic addition to bromoacetylation. Thus, we conclude that the control of the low reaction temperature is a key factor in favoring the nucleophilic addition to carbonyl and, therefore, obtaining a favorable conversion to functionalized PEG via bromoacetylation. Further studies, however, will be necessary to confirm whether PEG esterified with these conditions can be used in conjunction with molecules of a protein or peptide nature by means of bimolecular nucleophilic substitution.

RESUMEN La PEGilación, una reacción química de conjugación con la molécula de polietilenglicol (PEG), ha sido ampliamente aplicada por las industrias farmacéuticas como una estrategia para mejorar las propiedades farmacocinéticas de los compuestos bioactivos. El PEG es un polímero formado por un esqueleto de poliéter químicamente inerte con grupos hidroxilo (-OH) en sus extremos. Por lo tanto, para usar el PEG como reactivo de conjugación debe activarse con un grupo funcional que sea reactivo. En este sentido, la bromoacetilación es una alternativa para la funcionalización de PEG. De esta manera, en este trabajo nuestro objetivo es describir en detalle los procedimientos y el mecanismo de reacción involucrados en la funcionalización de PEG a través de la reacción de bromoacetilación. Además, estudiamos la aplicación de MALDI-ToF para la caracterización del producto activado. Después de aplicar un procedimiento de bromoacetilación adaptado, se obtuvo bromoacetil-mPEG-éster con un rendimiento bruto de 56,78%. Los análisis posteriores de espectrometría de masas por MALDI-ToF pudieron identificar y caracterizar correctamente el producto bromoacetilado. Entre las condiciones de reacción, el control de la temperatura (desde -10 °C hasta 0 °C) fue eficaz para favorecer la adición nucleofílica esencial a la bromoacetilación. Así, concluimos que el control de la baja temperatura de reacción es un factor clave para favorecer la adición nucleofílica al carbonilo y, por lo tanto, esencial para obtener el mPEG funcionalizado mediante la bromoacetilación. Sin embargo, serán necesarios más estudios para confirmar si el mPEG esterificado en estas condiciones puede usarse junto con moléculas de naturaleza proteica o peptídica por medio de la sustitución nucleófila bimolecular.

Synchronization of germinal vesicle maturity improves efficacy of in vitro embryo production in Holstein cows.

Germinal vesicle oocytes obtained by ovum pick-up (OPU) on a random day are heterogeneous in terms of chromatin maturity, and those with an intermediate degree of chromatin compaction present higher developmental competence. We previously developed a synchronization protocol combining follicle aspiration and FSH treatment capable of increasing the percentage of oocytes with intermediate chromatin compaction (classified as GV2 oocytes; within progressive stages of chromatin compaction ranging from GV0 to GV3) at the time of OPU. In this study, we tested the capacity of a similar protocol to synchronize oocyte chromatin maturity before OPU, as well as to improve the efficacy of in vitro embryo production (IVP) in Holstein cows. In the first experiment, eight non-lactating Holstein cows were subjected to the D5/4FSH, during which all follicles larger than 2 mm were aspirated and a progesterone intravaginal device was inserted on a random day (day 0). Subsequently, four IM injections of FSH (Folltropin; 40/40/20/20 mg) were administered 12h apart on days 2 and 3, and removal of the progesterone device and OPU were performed on day 5. Of the oocytes recovered by OPU, 83.2% were at the GV2 stage. In a second experiment, eighteen non-lactating Holstein cows (Synchro group) were subjected to the D5/4FSH protocol followed by IVM/IVF, and embryo production was compared with that of other seventeen cows submitted to OPU on a random day followed by IVM/IVF (Control group). Blastocyst rate in relation to total oocytes recovered was higher in the Synchro group (37.9%) compared to the Control group (21%; P < 0.05). The percentage of good quality blastocysts morphologically selected for freezing and later transfer in relation to the total number of oocytes recovered tended to be higher in the Synchro group (27.68%) compared to the Control group (14.34%; P = 0.1). These data suggest that synchronization protocols increasing the percentage of GV2 oocytes in the population subjected to IVM/IVF can improve the efficacy of embryo in vitro production in cattle.

Characterization and control of oocyte large-scale chromatin configuration in different cattle breeds.

Differences in reproductive physiology between cattle breeds may help to explain distinct responses to assisted reproductive techniques and to define breed-specific protocols with improved efficiency. Germinal vesicle (GV) stage oocytes are characterized by increasing levels of chromatin compaction enclosed within the nucleus (graded from GV0 to GV3), associated with different developmental competence. The first objective of this study was to characterize chromatin configuration of GV stage oocytes recovered by OPU at random days of the estrous cycle from Nelore (Bos indicus) and Holstein (Bos taurus) cows. In Nelore 90% of the oocytes presented advanced stages of chromatin compaction associated with higher developmental competence (GV2 and GV3), while in Holstein, only 65% of the oocytes were at these stages. Then, aiming to obtain a more homogeneous population of oocytes in Holstein, we tested two synchronization protocols combining aspiration of all visible follicles at a random day (day 0), two IM injections of FSH 12 h apart on day 2, and OPU on day 4 (OPU/D4) or 5 (OPU/D5). The protocol OPU/D4 provided around 45% of the oocytes with low chromatin compaction (GV1), while the protocol OPU/D5 provided 70% of the oocytes at GV2 and 20% at GV3. Finally, we assessed the effects of a culture system known to prevent meiotic resumption on chromatin configuration of the GV2 enriched oocyte population obtained with the protocol OPU/D5. After 9 h of culture most oocytes transited from GV2 to GV3, with 90% of the oocytes at GV3 stage. This study demonstrates differences between Nelore and Holstein cows regarding patterns of chromatin configuration that may account for their different performance in IVM/IVF. In addition, it provides novel references for the design of protocols aiming to regulate oocyte quality before IVM for the optimization of IVF outcomes.

Perfil medicamentoso de pessoas com hipertensão arterial / Medication profile of people with hypertension

Objective: to characterize the medication profile of people with hypertension followed-up by the Family Health Strategy (ESF). Method:A cross-sectional study with 417 people in the municipality of Maringá, located in the northwestern part of the state of Paraná, Brazil. Data collection took place in the first semester of 2016. An instrument was used to evaluate the satisfaction of users with arterial hypertension on the services provided by Primary Health Care (APS). In this study, only questions related to sociodemographic and drug profile were used. In the data analysis, descriptive statistics were applied. Results:there was a prevalence of the elderly (62.3%), most female (67.9%), with complete primary schooling (78.4%), color/race white (62.3%), retirees/pensioners (55.2%), predominance of individuals with partners (58.3%) and economically classified in C level (43.9%). Regarding medication, 34.8% were classified as polypharmacy and 58.8% received medication by the public health system. The most commonly used drugs were those of the cardiovascular, nervous, digestive and metabolic system. Conclusion:Through this study, it was possible to know the medication profile of patients with hypertension, which contributes to the adequate follow-up of patients in the basic healthcare network.

Objetivo: caracterizar o perfil medicamentoso de pessoas com hipertensão arterial acompanhadas pela Estratégia Saúde da Família (ESF). Método: estudo transversal realizado com 417 pessoas, no município de Maringá, localizado no noroeste do estado do Paraná, Brasil. A coleta de dados foi realizada no primeiro semestre de 2016. Foi utilizado um instrumento para avaliar a satisfação de usuários com hipertensão arterial com os serviços prestados pela Atenção Primária à Saúde (APS). Neste estudo, foram usadas somente as questões referentes ao perfil sociodemográfico e medicamentoso. Na análise dos dados, aplicou-se estatística descritiva. Resultado: houve prevalência de idosos (62,3%), grande parte do sexo feminino (67,9%), com até o ensino fundamental completo (78,4%), da raça/cor branca (62,3%), aposentados/pensionistas (55,2%), predomínio de indivíduos com companheiro (58,3%) e classificados economicamente em extrato C (43,9%). Em relação aos medicamentos, 34,8% foram classificados em polifarmácia e 58,8% receberam a medicação pelo sistema público de saúde. Os remédios mais utilizados foram os do grupo do sistema cardiovascular, nervoso, digestivo e metabólico. Conclusão: através deste estudo, foi possível conhecer o perfil medicamentoso de pacientes com hipertensão, o que contribui para o acompanhamento adequado de pacientes da rede básica de assistência à saúde.

Fibroblast growth factor 2 regulates cumulus differentiation under the control of the oocyte.

PURPOSE: We first assessed regulation of FGF2 expression in cumulus cells by FSH and oocyte-secreted factors during in vitro maturation (IVM). Then, we tested the hypothesis that FGF2 regulates meiotic progression, cumulus expansion, and apoptosis in cumulus-oocyte complexes (COC) undergoing IVM. METHODS: In vitro maturation of bovine COC was utilized as a model to assess regulation of FGF2 expression by FSH and oocyte-secreted factors (via microsurgical removal of the oocyte), as well as effects of graded doses of FGF2 on meiotic progression, degree of cumulus expansion, dissociation of cumulus cells, and cumulus cells apoptosis. Expression of genes regulating functional endpoints altered by FGF2 treatment was assessed in cumulus cells by real-time PCR. Cultures were replicated 4-5 times and effects of treatments were tested by ANOVA. RESULTS: FGF2 mRNA expression was increased by FSH and oocyte-secreted factors during IVM. Addition of FGF2 to the IVM medium advanced meiosis resumption, decreased the ease with which cumulus cells were dissociated, and inhibited cumulus cells apoptosis. Decreased cumulus dissociation was accompanied by decreased expression of TNFAIP6. CONCLUSIONS: This is the first study showing that FGF2 expression is regulated by the oocyte in cumulus cells. Moreover, we report novel effects of FGF2 on cumulus cell survival and extracellular matrix (ECM) quality during IVM that may favor acquisition of developmental competence and suggest physiological roles during the final steps of COC differentiation.

Steroid hormones interact with natriuretic peptide C to delay nuclear maturation, to maintain oocyte-cumulus communication and to improve the quality of in vitro-produced embryos in cattle.

In vivo, oocyte maturation is triggered by the ovulatory LH surge, whereas in vitro it is precociously induced when the cumulus-oocyte complex is removed from the follicle. Natriuretic peptide C (NPPC) delays germinal vesicle breakdown (GVBD) while increasing oocyte-cumulus communication during in vitro maturation (IVM) in cattle. In the present study we first tested the hypothesis that steroids secreted by the follicle (17ß-oestradiol, progesterone and androstenedione) interact with NPPC to delay GVBD and to maintain oocyte-cumulus communication as assessed by transfer of a dye (Lucifer Yellow) from the oocyte to cumulus cells. Then, we assessed the effects of steroid hormones and NPPC, alone and in combination in a pre-IVM culture, on embryo production. The combination of NPPC with steroids delayed GVDB, increased natriuretic peptide receptor 2 (NPR2) mRNA abundance in cumulus cells during culture, and maintained oocyte-cumulus communication at levels not different from non-cultured controls. The addition of steroids and/or NPPC to a pre-IVM culture did not alter blastocyst rates after IVF, but supplementation with steroids increased blastocyst total cell number. The present study provides evidence, for the first time in cattle, that steroids interact with NPPC to regulate oocyte nuclear maturation and oocyte-cumulus communication, and improve oocyte developmental competence.

Follow-up of children with hemoglobinopathies diagnosed by the Brazilian Neonatal Screening Program in the State of Pernambuco.

OBJECTIVE: To determine the geographical distribution of hemoglobinopathies in the State of Pernambuco, to characterize the children with these diseases and to describe factors associated with their follow-up at the referral center during the period from 2003 to 2010. METHODS: A retrospective, cross-sectional, descriptive study was carried out of 275 medical records from a total of 302 children with hemoglobinopathies diagnosed by the National Neonatal Screening Program in the State of Pernambuco in the study period. Microsoft Excel was used for data processing and analysis. The chi-square and the Fisher test were used for statistical analysis. The level of significance was set at 5%. Terra View software was used to analyze the geographical distribution of hemoglobinopathies in the State. RESULTS: A total of 8.9% of the cases of hemoglobinopathies detected in the period were not followed up at the referral center. For the mothers of children with diseases, this was their second or third or more pregnancy in 64.2% and 30.2%, respectively. Regarding the influence of region of residence and regular medical appointments, the study demonstrated that children from the Zona da Mata, Sertão and Vale do São Francisco regions did not attend 45.2%, 50% and 55.6% of their appointments in the outpatient department, respectively. CONCLUSIONS: This study shows that a significant number of children do not begin consultations in the outpatient clinic and even those who started treatment early and who have the most severe form of the disease, usually miss medical appointments.

Follow-up of children with hemoglobinopathies diagnosed by the Brazilian Neonatal Screening Program in the State of Pernambuco

OBJECTIVE: To determine the geographical distribution of hemoglobinopathies in the State of Pernambuco, to characterize the children with these diseases and to describe factors associated with their follow-up at the referral center during the period from 2003 to 2010. METHODS: A retrospective, cross-sectional, descriptive study was carried out of 275 medical records from a total of 302 children with hemoglobinopathies diagnosed by the National Neonatal Screening Program in the State of Pernambuco in the study period. Microsoft Excel was used for data processing and analysis. The chi-square and the Fisher test were used for statistical analysis. The level of significance was set at 5%. Terra View software was used to analyze the geographical distribution of hemoglobinopathies in the State. RESULTS: A total of 8.9% of the cases of hemoglobinopathies detected in the period were not followed up at the referral center. For the mothers of children with diseases, this was their second or third or more pregnancy in 64.2% and 30.2%, respectively. Regarding the influence of region of residence and regular medical appointments, the study demonstrated that children from the Zona da Mata, Sertão and Vale do São Francisco regions did not attend 45.2%, 50% and 55.6% of their appointments in the outpatient department, respectively. CONCLUSIONS: This study shows that a significant number of children do not begin consultations in the outpatient clinic and even those who started treatment early and who have the most severe form of the disease, usually miss medical appointments...