Randomized Controlled Trial Design Based on Patient Cohorts： Methods and Applications of Trials Within Cohorts / 中国实验方剂学杂志

Trials within cohorts （TwiCs） are design methods derived from randomized controlled trials （RCTS）. They have been widely used in chronic disease areas such as tumors and cardiovascular diseases. The basis of the TwiCs design is a prospective cohort of specific diseases. When RCTS need to be implemented， some patients meeting the inclusion and exclusion criteria are randomly sampled from the cohort to receive "trial interventions"， while the remaining patients in the cohort who meet the inclusion and exclusion criteria continue to receive conventional treatment as control groups. By comparing the efficacy differences between the intervention measures of the trial group and the control group， the efficacy of intervention measures was evaluated. Within the cohort， the same process could be repeated to carry out multiple RCTS， so as to evaluate different intervention measures or compare the efficacy of different doses or timing of interventions. Compared with classical RCTS， TwiCs make it easier to recruit patients from the cohort and have higher external validity， providing a new research paradigm for improving the efficiency and applicability of RCTS in clinical practice. However， TwiCs may also face the challenge of poor compliance of patients in the cohort. Researchers need to take effective measures to control these patients in the design and operation of TwiCs. This article focused on the methodological key points during the implementation of TwiCs， including multi-stage informed consent （patients are informed of consent at three stages： entering the cohort， entering the trial group， and after the trial）， randomization procedures （only random sampling of patients from the cohort to receive "trial interventions"）， sample size calculation， and statistical analysis methods. The article also compared the differences between TwiCs and traditional RCTS and illustrated TwiCs research design and analysis with examples， so as to provide new research ideas and methods for clinical researchers.

Identification of de novo Mutations in the Chinese Autism Spectrum Disorder Cohort via Whole-Exome Sequencing Unveils Brain Regions Implicated in Autism / 神经科学通报·英文版

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors. Although hundreds of ASD risk genes, implicated in synaptic formation and transcriptional regulation, have been identified through human genetic studies, the East Asian ASD cohorts are still under-represented in genome-wide genetic studies. Here, we applied whole-exome sequencing to 369 ASD trios including probands and unaffected parents of Chinese origin. Using a joint-calling analytical pipeline based on GATK toolkits, we identified numerous de novo mutations including 55 high-impact variants and 165 moderate-impact variants, as well as de novo copy number variations containing known ASD-related genes. Importantly, combined with single-cell sequencing data from the developing human brain, we found that the expression of genes with de novo mutations was specifically enriched in the pre-, post-central gyrus (PRC, PC) and banks of the superior temporal (BST) regions in the human brain. By further analyzing the brain imaging data with ASD and healthy controls, we found that the gray volume of the right BST in ASD patients was significantly decreased compared to healthy controls, suggesting the potential structural deficits associated with ASD. Finally, we found a decrease in the seed-based functional connectivity between BST/PC/PRC and sensory areas, the insula, as well as the frontal lobes in ASD patients. This work indicated that combinatorial analysis with genome-wide screening, single-cell sequencing, and brain imaging data reveal the brain regions contributing to the etiology of ASD.

Dinâmica comparada: fluxos dos escravizados africanos em São Paulo, Minas Gerais e Maranhão (1804-1848) / Comparative dynamics: flows of enslaved Africans in São Paulo, Minas Gerais and Maranhão (1804-1848) / Dinámica comparada: flujos de africanos esclavizados en São Paulo, Minas Gerais y Maranhão (1804-1848)

Analisamos comparativamente informes demográficos de qualidade aceitável acerca dos escravizados nascidos na África para Minas Gerais, São Paulo e Maranhão de 1804 a 1848. As parcelas dos nascidos na África em relação aos escravizados e às razões de sexo de todos os cativos, de acordo com as idades, auxiliaram-nos a remontar a dinâmica retrospectiva da chegada dos africanos às regiões. Supondo certas hipóteses e procedimentos, a partir das coortes etárias, estimamos as proporções de africanos e as razões de sexo da população cativa para os períodos anteriores aos das listas nominativas de habitantes. A dinâmica retrospectiva da introdução de africanos reconstruída mostrou-se bastante correlacionada à história econômica das diferentes regiões estudadas.

We compare the surviving enslaved people present in demographic censuses of acceptable quality for Minas Gerais, São Paulo and Maranhão from 1804 to 1848. The share of those born in Africa in relation to slaves and the sex ratio of all captives according to their ages helped us find the retrospective dynamics of the arrival of Africans to these regions. When using age cohorts, we estimate, assuming certain hypotheses and procedures, the proportions of Africans and the sex ratios of the captive population for periods prior to those of the nominative lists of inhabitants. The retrospective dynamics of the reconstructed introduction of these Africans proved to be closely correlated with the economic history of the different regions analyzed.

Analizamos comparativamente a los sobrevivientes esclavizados presentes en los informes demográficos evaluados como de calidad aceptable para Minas Gerais, São Paulo y Maranhão entre 1804 y 1848. La proporción de los nacidos en África en relación con los esclavizados y la proporción de sexos de todos los cautivos, según las edades, nos ayudaron a trazar la dinámica retrospectiva de la llegada de africanos a estas regiones. Utilizando las cohortes de edad, estimamos, asumiendo ciertas hipótesis y procedimientos, las proporciones de africanos y las proporciones de sexos de la población cautiva para períodos anteriores a las listas nominativas de habitantes. La dinámica retrospectiva de la introducción reconstruida de africanos demostró estar altamente correlacionada con la historia económica de las diferentes regiones estudiadas.

Estrato sociodemográfico y patrones relacionados con la primera unión o la primera maternidad en México, 2018 / Sociodemographic strata and patterns related to the first union and first motherhood in Mexico, 2018

Resumen: Introducción: Eventos como la primera unión o la primera maternidad son acontecimientos claves que marcan la transición a la vida adulta de las mujeres, por lo que el objetivo de este trabajo fue investigar las pautas de formación familiar de dos generaciones de mujeres en México, según el estrato sociodemográfico. Metodología: Para este estudio, se analizaron los datos de la Encuesta Nacional de la Dinámica Demográfica de 2018. Inicialmente, se estudia la intensidad y el calendario de los dos eventos mediante el análisis de supervivencia. Finalmente, para determinar si el estrato sociodemográfico está asociado a la ocurrencia del calendario de los dos eventos se ajusta un modelo de riesgos proporcionales de Cox. Resultados: Se observa que las mujeres nacidas entre 1984 y 1988, pertenecientes a los estratos sociodemográficos más bajos, tienen los mismos comportamientos demográficos que aquellas mujeres del mismo estrato que nacieron veinte años antes. Es importante señalar que las que pertenecen a los estratos más altos han postergado la entrada de estos dos eventos, tan importantes desde la perspectiva social y cultural de México. Conclusiones: Las pautas de los comportamientos demográficos relacionados con la formación de la familia en México ratifican que es un país con pautas culturales, sociales y familiares bien establecidas, que aún en las generaciones más jóvenes se siguen transmitiendo. Por lo que es de suma importancia seguir estudiando más afondo el tema de la estabilidad del calendario y la intensidad de la primera unión o la primera maternidad.

Abstract: Introduction: The first union and the first motherhood are key events that start the women's transition to adulthood, so that the aim of this paper is investigating the family formation´s patterns in Mexico, specifically in the first union and the first maternity of two women´s generations, analyzing quantum and tempo according to the sociodemographic stratum. Methodology: This study analyzes the National Survey of Demographic Dynamics of 2018. Initially, the two events' quantum and tempo are studied by the survival analysis. Finally, to determine if the sociodemographic stratum is associated with the occurrence of the calendar of events, two Cox proportional hazards models are adjusted. Results: It can be observed that women born between 1984 and 1988, located among the lowest sociodemographic strata have the same demographic behaviors as those women of the same stratum who were born twenty years earlier. It is important to see that those women who belong to the highest strata have postponed the entry of these two events, so important from the social and cultural perspective of Mexico. Conclusions: The demographic behavior's patterns related to family formation in Mexico ratify that this is a country with very established cultural, social and family behavior standards, that even in the younger generations these patterns continue to be transmitted. Therefore, it is very important to continue analyzing the tempo and the quantum of the first union and the first motherhood.

Postembrionic development and reproductive parameters of the grasshopper pest Borellia bruneri (Acrididae: Gomphocerinae) under controlled conditions

Abstract Borellia bruneri, a common grasshopper in much of the grasslands of Argentina and Uruguay, is considered, according to the categories widely accepted for defining the pest status of grasshopper species, a "Frequent plague of importance". In order to determine fundamental aspects of its biology and reproduction, three cohorts of B. bruneri were monitored under controlled conditions (30º C, 14L: 10D, 40% RH). The total duration of nymphal development was 50.6 days, both males and females having five nymphal instars. There was a significant difference in the duration of the different stages within each cohort. In the three cohorts, the first instar duration (12.87 days) was longer than the rest, approximately 5.6 days more than the second that was the shortest (7.26 days). The average longevity of female adults was 56.6 days, and in males, 54.4 days. The number of egg-pods per female was 3.5 and the amount of eggs per egg-pod was 10.8. Mean fecundity was 37.9 eggs per female with an oviposition rate of 1.20 eggs/female/day. Finally, knowing the life cycle of B. bruneri is relevant in order to optimize the control measures for this species.

Factors associated with exclusive breastfeeding practice in a cohort of women from Cali, Colombia / Factores asociados con la práctica de lactancia exclusiva en una cohorte de mujeres de Cali, Colombia

Abstract Introduction: Breastfeeding promotion is one of the most effective strategies to prevent child malnutrition; it reduces costs to families, health services and society. In Colombia, exclusive breastfeeding is practiced only by 10% of women. Objective: To identify factors associated with the duration of exclusive breastfeeding. Methods: A cohort of 438 primiparous women was followed during 6 months by means of 8 home interviews, in order to determine the duration of exclusive breastfeeding. Individual, family and health service factors were studied; and survival analysis was carried out. Results: At 8 days, only a few more than half of the participants maintained exclusive breastfeeding; at month 6 of follow-up, this proportion was reduced to 1.4%. The duration of exclusive breastfeeding was determined by: initiation of breastfeeding in the first 4 hours after delivery (HR= 4.07, 95% CI: 0.96-16.67), self-perceived sureness for breastfeeding (HR= 1.28, 95% CI: 1.04 -1.58), positive opinion of the baby's father regarding breastfeeding (HR= 1.26, 95% CI: 1.01-1.57), and newborn weight (HR= 1.23, 95% CI: 1.00-1.53). Conclusion: There are factors before delivery and in the immediate puerperium that determine, partially, the duration of exclusive breastfeeding.

Resumen Introducción: La promoción de la lactancia es una de las estrategias más efectivas para evitar la desnutrición infantil; reduce costos a las familias, los servicios de salud y la sociedad. En Colombia solo 10% de las mujeres practican la lactancia materna exclusiva. Objetivo: Identificar factores asociados a la duración de la lactancia exclusiva. Métodos: Se siguió durante 6 meses a una cohorte de 438 mujeres primíparas mediante 8 entrevistas domiciliarias para determinar la duración de lactancia exclusiva. Se estudiaron factores individuales, familiares y de servicios de salud y se realizó análisis de sobrevida. Resultados: A los 8 días sólo un poco más de la mitad de participantes mantenía lactancia exclusiva; al mes 6 de seguimiento esta proporción se redujo a 1.4%. La duración de lactancia exclusiva estuvo determinada por: inicio de lactancia en las primeras 4 horas pos-parto (HR= 4.07; IC 95%: 0.96-16.67), seguridad auto-percibida para amamantar (HR= 1.28; IC 95%: 1.04-1.58), opinión positiva del padre del bebé frente a lactancia (HR= 1.26; IC 95%: 1.01-1.57) y peso de recién nacido (HR= 1.23; IC 95%: 1.00-1.53). Conclusión: Existen factores antes del parto y en el puerperio inmediato que determinan, parcialmente, la duración de la lactancia exclusiva.

Population dynamics of Rimapenaeus constrictus (Stimpson, 1874) (Penaeoidea) on the southeastern Brazilian coast: implications for shrimp fishing management from a 5-year study on a bycatch species

ABSTRACT This is the first study to evaluate in broad spatiotemporal scales the growth parameters and population structure of Rimapenaeus constrictus, a barely damaged species composing the bycatch from shrimp fishing in the Western Atlantic. The abundance and size-class frequency distribution, growth, longevity and sex ratio were evaluated from monthly samples obtained in the northern littoral of São Paulo state from Jan/1998 to Jun/2003. We measured 5,812 individuals in which the sex ratio was skewed toward females; this was more evident in size classes greater than 10 mm in CL (carapace length) (binomial test, p<0.05). We selected 16 growth cohorts of females, and 8 of males, the majority consisting of younger individual cohorts excluded from the fisheries closure period. Growth estimates resulted in a CL∞ of 17.42 mm, a growth coefficient of 0.008 and a longevity of 579 days (1.60 year) for females, as well as a CL∞ of 16.3 mm, a growth coefficient of 0.01 and a longevity of 425 days (1.17 year) for males. Our results provide information of incontestable relevance to our knowledge of fishing management. We therefore strongly recommend that the fisheries closure period be changed to protect this species' recruitment period and consequently its adult individuals.

The national rare diseases registry system of China and the related cohorts studies:vision and roadmap / 中华内分泌代谢杂志

[Summary] Rare diseases are one of the major challenges we face today in the era of precision medicine, because of the low incidence and prevalence, difficulty in diagnosis, lack of sufficient therapeutic methods, as well as their significant impacts on affected individuals, families and the society. Integration of clinical phenotypic and biological omics data and the further analysis are providing a way to illustrate the mechanisms of rare diseases, discovering novel diagnostic and prognostic biomarkers, developing orphan drugs and other therapeutics, and improving clinical outcomes and quality of life for the patients. A nation-wide registry system and the cohorts studies based on the registry are vital to the research of rare diseases. National Rare Diseases Registry System ( NRDRS) of China will provide this essential platform to promote the rare diseases research in China. With the collaboration of 20 leading medical institutes and innovation in medical informatics technologies, this system will, for the first time in China, collect the epidemiological, clinical, socio-economical, genomics and metabolomics data of more than 50 rare diseases and not less than 50 000 cases. As a national strategy for enhancing the development of medical sciences and the improvement of population health in China, NRDRS and its cohort studies will provide the pivotal support to policy making, clinical care, novel drug discovery, patient advocacy, and finally scientific progress in the field of rare diseases.

Herdabilidade da velocidade de onda de pulso e associação do controle glicêmico e perfil lipídico com a rigidez arterial em uma população brasileira: "Projeto Corações de Baependi" / Heritability of pulse wave velocity and association of glycemic control and lipid profile with arterial stiffness in a Brazilian population

A rigidez arterial aumentada é um importante determinante do risco cardiovascular e um forte preditor de morbimortalidade. Além disso, estudos demonstram que o enrijecimento vascular pode estar associado a fatores genéticos e metabólicos. Portanto,os objetivos do presente estudo são determinar a herdabilidade da velocidade de onda de pulso (VOP) e avaliar a associação do perfil lipídico e do controle glicêmico com o fenótipo de rigidez arterial em uma população brasileira. MÉTODOS: Foram selecionados 1675 indivíduos (ambos os gêneros com idade entre 18 e 102 anos) distribuídos em 109 famílias residentes no município de Baependi-MG. A VOP carótida-femoral foi avaliada de forma não invasiva através de um dispositivo automático. As variáveis lipídicas e a glicemia de jejum foram determinadas pelo método enzimático colorimétrico. Os níveis de hemoglobina glicada (HbA1c) foram determinados pelo método de cromatografia líquida de alta eficiência. As estimativas da herdabilidade da VOP foram calculadas utilizando-se a metodologia de componentes de variância implementadas no software SOLAR. RESULTADOS: A herdabilidade estimada para a VOP foi de 26%, sendo ajustada para idade, gênero, HbA1c e pressão arterial média. Os níveis de HbA1c foram associados a rigidez arterial, onde a elevação de uma unidade percentual da HbA1c representou um incremento de 54% na chance de risco para rigidez arterial aumentada. As variáveis lipídicas (LDL-c, HDL-c, colesterol não- HDL-c, colesterol total e triglicérides) apresentaram fraca correlação com a VOP. Além disso, uma análise de regressão linear estratificada para idade (ponto de corte >= 45 anos) demonstrou uma relação inversa entre LDL-c e VOP em mulheres com idade >= 45 anos. CONCLUSÃO: Os resultados indicam que a VOP apresenta herdabilidade intermediária (26%); a HbA1c esta fortemente associada a rigidez arterial aumentada; o LDL-c é inversamente relacionado com a VOP em mulheres com idade >= 45 anos...

Increased central arterial stiffness is an important determinant of cardiovascular risk and a strong predictor of morbimortality. Moreover, studies showed that vascular stiffening can be associated with genetic and metabolic factors. Thus, the aims of this study are to estimate the heritability of pulse wave velocity (PWV) and to assess the association of lipid profile and glycemic control with arterial stiffness in a sample from the Brazilian population. METHODS: For this study, 1675 individuals (both genders aged from 18 to 102 years) were selected and they were distributed within 109 families residents in the municipality of Baependi - MG. The PWV was measured with a non-invasive automatic device. Lipid profile parameters and fasting glucose were determined by enzymatic colorimetric method. HbA1c levels were determined by high-performance liquid chromatography. Variance component approaches implemented in the SOLAR software were applied to estimate the heritability of PWV. RESULTS: Heritability estimates for carotid-femoral PWV was 26%, after adjustment for age, gender, HbA1c, and mean blood pressure. HbA1c levels were associated with arterial stiffness and the elevation of a single unit percentage of HbA1c represented an increase of 54 % in the odds of increased arterial stiffness. The lipid variables (LDL-c, HDL-c, non-HDL-c, total cholesterol and triglycerides) presented weak correlation with PWV. In addition, a linear regression analysis stratified by age (cutoff >= 45 years) showed an inverse relation between LDL-c and PWV in women aged 45 or older. CONCLUSION: Our findings indicate that PWV demonstrated an intermediate heritability (26%); HbA1c proved to be a good marker for risk stratification for increased arterial stiffness; LDL-c was inversely related with PWV in women aged 45 or older, possibly due to the metabolic alterations associated with ovarian failure...

La medicina personalizada, la revolución genómica y el Sistema Nacional de Salud / Customized medicine, genomic revolution and the national health care system

La profundización del conocimiento de los mecanismos moleculares del proceso salud-enfermedad ha hecho que avances científicos hayan encontrado lugar en la práctica clínica, como ha ocurrido en Cuba con las células madre. Los resultados derivados de la secuenciación del genoma humano y de otras especies mejora diagnósticos y tratamientos, sin embargo, dentro del sistema sanitario cubano no abundan las aplicaciones de las tecnologías genómicas. Esta nueva medicina necesita acumular todavía evidencia acerca de su seguridad y eficacia, se requiere una estrategia propia del Ministerio de Salud Pública en relación con la evaluación de sus usos, presentes y potenciales, en beneficio de la salud de la población. Se propone, entre otras acciones, constituir un grupo de trabajo multiinstitucional e intersectorial para estudiar las dimensiones clínicas, tecnológicas, reguladoras y bioéticas de la medicina genómica. Resulta imprescindible la preparación inmediata del personal que estudia en el pregrado o ya ejerce en las ciencias médicas, pues corresponderá a ellos la introducción y la extensión de estas tecnologías en el ejercicio de su práctica profesional. De manera inmediata es posible conformar cohortes que sean representativas de la población cubana, estudiarlas y conservar sus muestras en biobancos establecidos para tales fines. La progresiva introducción de las aplicaciones en la práctica clínica de la genómica y las tecnologías relacionadas, reclama del Sistema Nacional de Salud una atención que conduzca al estudio, la evaluación y propuesta de las acciones que permitan su implementación, según las evidencias y las condiciones y necesidades del modelo cubano de atención sanitaria(AU)

Deepening into the knowledge of the molecular mechanisms of the health/disease process has made many scientific advances to find a place into the clinical practice, as is the case of stem cells therapy in Cuba. The results derived from the sequencing of the human genome, as well of other species, have had an impact in the improvement of diagnoses and therapies; however, within the Cuban national health system the applications of genomic technologies are not widespread. Despite the fact that this new medicine still needs to accumulate much more evidence supporting its safety and efficacy, it is urgent to design a customized strategy by the Cuban Ministry of Public Health towards the assessment of current and potential uses of genomic medicine for the benefit of the population's health. Among other actions, this paper submitted the proposal of the creation of a multi-institutional and intersectoral taskforce to study the clinical, technological, regulatory and bioethical dimensions of genomic medicine. It is mandatory to train both undergraduate students and staff since they will be responsible to introduce and extend such technologies in their professional practice. It is already possible to make up cohorts resembling as much as possible the Cuban population, to study them and to collect and preserve their samples in biobanks established for such purposes(AU)

Estrutura social e transmissão intergeracional de status: uma análise hierárquica / Estructura social y transmisión intergeneracional de status: un análisis jerárquico / Social structure and intergenerational transmission of status: a hierarchical analysis

A investigação dos mecanismos de transmissão de status tem correspondido à grande parte dos esforços dos estudos empíricos dos sistemas de estratificação. As diferenças organizacionais encontradas entre setores econômicos e as diferenças regionais inserem-se justamente na dimensão estrutural dos estudos de estratificação. Assim, o principal objetivo deste artigo é investigar em que medida o status ocupacional atual dos indivíduos foi afetado pela sua origem social, considerando-se o momento em que estes indivíduos se inseriram no mercado de trabalho e onde se inseriram. Foram utilizadas as bases da Pesquisa Nacional por Amostra de Domicílios (PNAD) de 1973, 1982, 1988 e 1996 e estimados Modelos Hierárquicos que representam, para os estudos de transmissão intergeracional de status, a possibilidade de um melhor controle de fatores estruturais. Observou-se que a segmentação do mercado de trabalho em diferentes setores econômicos e o nível de crescimento econômico no Brasil em diferentes coortes de entrada dos indivíduos no mercado de trabalho são mecanismos que funcionam como mediadores da transmissão de status, enquanto a segmentação regional não apresentou efeitos significativos.

Una gran parte de los esfuerzos realizados por los estudios empíricos de los sistemas de estratificación ha correspondido a la investigación de los mecanismos de transmisión de status. Las diferencias organizacionales encontradas entre sectores económicos y las diferencias regionales se insertan, precisamente, en la dimensión estructural de los estudios de estratificación. Así pues, el principal objetivo de este artículo es investigar en qué medida el status ocupacional actual de los individuos analizados se vio afectado por su origen social, teniendo en consideración el momento en el que estos individuos se insertaron en el mercado de trabajo y el lugar donde se produjo su inserción. Para ello, fueron utilizadas las bases de la Pesquisa Nacional por Amostra de Domicílios (PNAD¹) de 1973, 1982, 1988 e 1996 y se estimaron los modelos jerárquicos que representan, para realizar los estudios de transmisión intergeneracional de status, y analizar la posibilidad de un mejor control de factores estructurales. Se observó que la segmentación del mercado de trabajo, en diferentes sectores económicos, y el nivel de crecimiento económico en Brasil, en diferentes cohortes de entrada de los individuos en el mercado de trabajo, son mecanismos que funcionan como mediadores de la transmisión de status, mientras que en lo que se refiere a la segmentación regional no se presentaron efectos significativos.

Empirical studies of stratification systems have concentrated in investigating the mechanisms of transmission of status. Organizational differences found between economic sectors and regional differences fall precisely in the structural dimension of stratification studies. Thus, the main objective of this paper is to investigate to what extent the current occupational status of individuals was affected by their social origin, considering the time when and where these individuals entered the labor market. We used the databases from the National Household Sample Survey (PNAD in Portuguese) of 1973, 1982, 1988 and 1996, and estimated the Hierarchical Models that represent, for studies of intergenerational transmission of status, the possibility of better control of structural factors. We observed that the segmentation of the labor market in different economic sectors and the level of economic growth in Brazil in different cohorts of individuals entering the labor market are mechanisms that function as mediators for the transmission status while regional segmentation had no significant effect.

Sobrevida de pacientes portadores de mieloma múltiplo atendidos em hospital de referência no Sul de Santa Catarina / Survival of patients with multiple myeloma attended in a reference hospital in South Santa Catarina

JUSTIFICATIVA E OBJETIVOS: O mieloma múltiplo (MM) é uma proliferação maligna monoclonal de plasmócitos derivados de um único clone. Devido à variedade de disfunções orgânicas causada pela neoplasia e a não descoberta da cura, consequentemente a sobrevida torna-se um desafio para este grupo de pacientes. O objetivo deste estudo foi analisar o perfil epidemiológico e a sobrevida dos pacientes portadores de MM internados no hospital Nossa Senhora da Conceição (HNSC) da cidade de Tubarão entre 1998 e 2008. MÉTODO: Estudo retrospectivo, em que se revisaram os prontuários de pacientes portadores de MM atendidos no HNSC. A amostra foi composta por 46 pacientes, sendo excluídos os que mudaram o local de atendimento. A análise de sobrevida foi observada através do método de Kaplan-Meier e análise multivariada por regressão de Cox. RESULTADOS: A média de idade foi de 68,3 anos, 56,5% eram do sexo feminino, 78,3% brancos, 15,2% eram negros e 6,5% pardos. As manifestações clínicas mais comuns foram: dor óssea (93,5%), anemia (95,7%) e insuficiência renal (43,5%). Na análise de sobrevida, a única variável que obteve significância estatística foi insuficiência renal (p = 0,026). Para mortalidade, insuficiência renal (p = 0,018) e anormalidades da coagulação (p = 0,011) apresentaram significância na regressão de Cox. CONCLUSÃO: O perfil epidemiológico mostrou leve predominância no sexo feminino e com maior número de pacientes da cor branca. Dor óssea foi a queixa mais frequente. Insuficiência renal e anormalidade da coagulação tiveram associação com a mortalidade dos pacientes com MM.

BACKGROUND AND OBJECTIVES: The multiple myeloma (MM) is a monoclonal malignant proliferation of plasma cells that derive from a unique clone. Due to the variety of organic dysfunctions caused by this neoplasia and to the not discovered cure, consequently the survival becomes a challenge for this patients group. The objective of this study was to analyze epidemiologic profile and the survival of the patients who have MM attended at the hospital Nossa Senhora da Conceição (HNSC) in Tubarão city, South Brazil, between 1998 and 2008. METHOD: Retrospective study that revised the patients' handbooks with MM disease and that were taken care at HNSC. The sample was composed by 46 patients, being exclusion criteria patients that moved the attendance place. The analysis of survival was tested through the Kaplan-Meier method and the multivariate analysis by regression of Cox. RESULTS: The average age was of 68.3 years old, 56.5% was female, 78.3% white people, 15.2% black people and 6.5% mediums brown. The most common clinical manifestations were: bone pain (93.5%), anemia (95.7%) and renal insufficiency (43.5%). In the survival analysis, the only variable that presented statistic significance was renal insufficiency (p = 0.026). For mortality, renal insufficiency (p = 0.018) and abnormalities of the coagulation (p = 0.011) presented significance in the Cox regression.CONCLUSION: The epidemiologic profile showed a slight predominance in female and a higher number of white patients. Pain in the bones was the most frequent complaint. Renal insufficiency and abnormalities of the coagulation were associated with the mortality of the patients with MM.

Uso de alcohol, tabaco y drogas en población Mexicana, un estudio de cohortes

resumen está disponible en el texto completo

Summary: Introduction. The availability of drugs and its impact upon our society is undeniably a public concern; the question that remains is to what extent is the population affected. Different sources of information suggest that drug use in Mexico is increasing, especially among the adolescent population. As it has been thirty years since the first epidemiological study of drug use was conducted in Mexico in the 1970's, this is an opportune moment to evaluate the problem by age cohort. This research addresses the question of whether changes in substance use have differentially affected the younger population in terms of the evolution of ages of onset and the socio-demographic determinants of lifetime consumption. Method. This study is a part of the World Mental Health Surveys Initiative from the WHO which was undertaken simultaneously in 30 countries. The target population was taken from uninstitutionalized persons with a fixed residence, between 18 and 65 years of age, and living in urban areas (as defined by more than 2500 inhabitants). The survey is based on a probabilistic, multistage design, stratified by six geographic areas at the national level. Eligible respondents were defined as persons, aged 18 to 65 at the time of the survey, who normally eat, sleep and prepare meals in the household and limited to those that speak Spanish. A total of 5826 individuals were interviewed with a weighted individual response rate of 76.6%. The computer assisted version of the World Mental Health Composite International Diagnostic Interview (WMH-CIDI)was administered. The interview length varied from a minimum of 20 minutes to a maximum of nine hours in four sessions. Fieldwork was carried out by 34 lay interviewers with prior experience in survey data collection and trained by professionals certified by the WHO in the use and training of the CIDI. Standard errors of the estimated prevalences were calculated by the Taylor linearization method using the SUDAAN 2002 statistical package. Kaplan Meir survival curves were generated for the ages of onset using the SAS 2001 software. Logistic regressions were performed to study the demographic correlates of substance use. Estimates of standard errors of odds ratio (ORs) from logistic regression coefficients were also obtained by SUDAAN, and 95% Confidence Intervals (CI) have been adjusted to design effects. Results. Alcohol is the most used substance with less variation by age; 86% of those interviewed report alcohol consumption at some time in their life. The prevalence of alcohol use is followed by tobacco use. Sixty percent of the population report having used tobacco, reaching the greatest proportion of the population in the 45 to 54 year old age group (63%). The non-medical use of drugs, including illicit drugs and legal drugs without a medical prescription, reaches 10% of the population. The illegal use of drugs, including the non-medical use of legal drugs and illicit drugs, in particular marijuana and cocaine, is more frequent among the young and prevalence diminishes with age. Beginning in adolescence, there is a growing prevalence of those reporting the use of these substances, stabilizing shortly before the age of 30. A discrete time survival analysis to estimate the variation in the lifetime prevalence by cohort showed variations in drug use by cohort for all the substances studied, even for alcohol consumption. In all cases, compared to the oldest cohort, the younger cohort are at greater risk of substance use and the greatest risks are concentrated always in the youngest cohort. The cohort differences in probability of substance use is greatest for cocaine, with increases of up to 100 times the risk for those between 18 and 29 years of age. Results of a logistic regression model demonstrate that age continues to be an important risk factor for non-prescription medical substance use, marijuana and cocaine, but not for alcohol and tobacco. For all substances, use is substantially lower for females as well as for the homemaker category of employment. There are no consistent differences for the other demographic variables across the five types of substances. Discussion. This report documents an increase in the risk for substance abuse problems among today's youth, greater than the risk faced by their parents or grandparents at the same age. Use begins increasing during adolescence and stabilizes shortly before the age of 30. There are variations by type of drug such that marijuana has maintained an early age of onset in the different age cohorts while for the use of other substances new cases of onset are found after this age; the substance that shows the greatest proportion of new onset at later ages is cocaine. Even so, the risk of cocaine use is considerably greater in younger cohorts. Survival analysis confirms that compared to older cohorts, the younger have greater risk of substance use and these risks are particularly striking for cocaine use, with as much as 100 times the risk for those between 18 and 29 years of age. These findings coincide with those reported in previous studies in that alcohol and tobacco use surpass by far the use of other substances, with greater use of alcohol than tobacco and both above any other substance. The rate of tobacco and alcohol use is similar throughout the lifespan signifying that this is an endemic problem in our country. On the other hand, findings regarding the use of illegal drugs, in particular marijuana and cocaine, and non-prescription medical drugs show a preponderance of use in the young. These findings reflect the tendencies already reported in other studies. Marijuana use is not new, and has a long tradition throughout the country for which it is not surprising that these results show cases of consumption in all age groups and that the age of onset is similar in all age cohorts, around 17 years of age. However, the growth of marijuana use is reflected by greater lifetime prevalence in the young, three times greater among those now currently 18 to 29 years of age than those of the same age in the 1970's. The use of cocaine before that decade was limited to isolated groups as a socially sophisticated diversion; there is a resurgence in the 1990's when an important increase in use is reflected in all the available surveillance systems. This is reflected in our results by the lower exposure to this drug in the older cohorts. While the risk of marijuana use is 16 times lower in the older cohort than the younger, the risk of cocaine use is 100 times lower in the older cohort than the younger. Our findings suggest that age continues to be an important risk factor for the use of illegal drugs and medical drugs without a prescription, but not for alcohol or tobacco. For all substances, use is lower for females as well as for homemakers indicating that double standards between the genders are still applied. For alcohol there are slightly lower risks for those with lesser educational attainment. This is consistent with other studies which have documented that alcohol consumption increases with buying power which is in turn associated with increased education. These results suggest the need to undertake further research which would allow us a more in depth understanding of the role that social position, including marital status, plays in substance use and abuse. Conclusions. These findings support the hypothesis that the younger generation of today has a greater risk of substance use when compared to their parents when they were young. This point out to the need of increasing actions aimed at reducing the negative impact of this phenomena upon health and society.