Early Infant Morbidity in the City of São Paulo, Brazil

BACKGROUND: Early infant morbidities may produce adverse outcomes in subsequent life. A low Apgar score is a convenient measure of early infant morbidity. We study determinants of early infant morbidity (sex, plurality, mode of delivery, prior losses, gestational age, prenatal care and birth weight, parity and maternal age, race, maternal education and community development) for the 1998-birth cohort, City of São Paulo, Brazil. METHODS: This study identified all deliveries that took place in the City of São Paulo during 1998. Information was extracted from 209,628 birth records. We used multivariate logistic regression to assess the effect of each independent variable on Apgar score less than seven at one minute and Apgar score less than seven at five minutes. RESULTS: Low birth weight, prematurity and community development were found to be strong predictors of morbidity. Maternal education showed strong negative correlation with both Apgar scores. The negative correlations between maternal schooling and Apgar scores were observed after prenatal care, parity and maternal age were included in the model. Unmeasured proximate factors may thus be the true source of disparity between educational groups. Children of very young adolescent mothers had lower Apgar scores at one minute (but not at five minutes) than those born to mothers 15 to 19. Parity one or higher was associated with decreased odds of low Apgar scores. Cesarean section and operative delivery were associated with higher odds of early infant morbidity. CONCLUSION: Education may allow mothers to have better care in the peripartum period. More educated mothers may be more likely to recognize certain morbidities through the pregnancy period and the monitoring of such morbidities yields better infant outcomes. Also, having less than seven prenatal care visits was found to predict early infant morbidity and one way to increase the use of such services is to focus on aspects of care that may lead to easier accessibility and continuity of prenatal care. Physicians should inform mothers about the risks associated with high number of children for a next infant and also about the risks for the infant associated with unnecessary cesarean sections. Special attention should be paid to adolescent mothers, since much of their increased risk is likely to be minimized by counseling

Ebola: translational science considerations

We are currently in the midst of the most aggressive and fulminating outbreak of Ebola-related disease, commonly referred to as “Ebola”, ever recorded. In less than a year, the Ebola virus (EBOV, Zaire ebolavirus species) has infected over 10,000 people, indiscriminately of gender or age, with a fatality rate of about 50%. Whereas at its onset this Ebola outbreak was limited to three countries in West Africa (Guinea, where it was first reported in late March 2014, Liberia, where it has been most rampant in its capital city, Monrovia and other metropolitan cities, and Sierra Leone), cases were later reported in Nigeria, Mali and Senegal, as well as in Western Europe (i.e., Madrid, Spain) and the US (i.e., Dallas, Texas; New York City) by late October 2014. World and US health agencies declared that the current Ebola virus disease (EVD) outbreak has a strong likelihood of growing exponentially across the world before an effective vaccine, treatment or cure can be developed, tested, validated and distributed widely. In the meantime, the spread of the disease may rapidly evolve from an epidemics to a full-blown pandemic. The scientific and healthcare communities actively research and define an emerging kaleidoscope of knowledge about critical translational research parameters, including the virology of EBOV, the molecular biomarkers of the pathological manifestations of EVD, putative central nervous system involvement in EVD, and the cellular immune surveillance to EBOV, patient-centered anthropological and societal parameters of EVD, as well as translational effectiveness about novel putative patient-targeted vaccine and pharmaceutical interventions, which hold strong promise, if not hope, to curb this and future Ebola outbreaks. This work reviews and discusses the principal known facts about EBOV and EVD, and certain among the most interesting ongoing or future avenues of research in the field, including vaccination programs for the wild animal vectors of the virus and the disease from global translational science perspective

Evaluation of Calibration Curve-Based Approaches to Predict Clinical Inducers and Noninducers of CYP3A4 with Plated Human Hepatocytes

Cytochrome P450 (P450) induction is often considered a liability in drug development. Using calibration curve-based approaches, we assessed the induction parameters R3 (a term indicating the amount of P450 induction in the liver, expressed as a ratio between 0 and 1), relative induction score, Cmax/EC50, and area under the curve (AUC)/F2 (the concentration causing 2-fold increase from baseline of the dose-response curve), derived from concentration-response curves of CYP3A4 mRNA and enzyme activity data in vitro, as predictors of CYP3A4 induction potential in vivo. Plated cryopreserved human hepatocytes from three donors were treated with 20 test compounds, including several clinical inducers and noninducers of CYP3A4. After the 2-day treatment, CYP3A4 mRNA levels and testosterone 6beta-hydroxylase activity were determined by real-time reverse transcription polymerase chain reaction and liquid chromatography-tandem mass spectrometry analysis, respectively. Our results demonstrated a strong and predictive relationship between the extent of midazolam AUC change in humans and the various parameters calculated from both CYP3A4 mRNA and enzyme activity. The relationships exhibited with non-midazolam in vivo probes, in aggregate, were unsatisfactory. In general, the models yielded better fits when unbound rather than total plasma Cmax was used to calculate the induction parameters, as evidenced by higher R(2) and lower root mean square error (RMSE) and geometric mean fold error. With midazolam, the R3 cut-off value of 0.9, as suggested by US Food and Drug Administration guidance, effectively categorized strong inducers but was less effective in classifying midrange or weak inducers. This study supports the use of calibration curves generated from in vitro mRNA induction response curves to predict CYP3A4 induction potential in human. With the caveat that most compounds evaluated here were not strong inhibitors of enzyme activity, testosterone 6beta-hydroxylase activity was also demonstrated to be a strong predictor of CYP3A4 induction potential in this assay mode

ALMA, a new tool for the management of asthma patients in clinical practice: development, validation and initial clinical findings

BACKGROUND: Several instruments have been developed for measuring asthma control, but there is still a need to provide a structure for primary care asthma reviews. AIMS: The Active Life with Asthma (ALMA) tool was developed with the aim of structuring patient visits and assessing asthma treatment in primary care. The ability of ALMA to map out the care of asthma patients was evaluated and validated. METHODS: ALMA was developed with patient and clinical expert input. Questions were generated in focus groups and the resulting tool was subsequently validated by factor analysis in 1779 patients (1116 females) of mean age 51 years (range 18-89) in primary care. RESULTS: The ALMA tool includes 19 questions, 14 of which belong to a subset assessing asthma control. In this subset, factor analysis revealed three domains (factors): physical, psychological, and environmental triggers. Correlation with the Asthma Control Questionnaire was 0.72 and the Cronbach's alpha was 0.88. The test-retest reliability was 0.93. Of the 1779 patients tested with ALMA in primary care, 62% reported chest tightness, 30% nightly awakenings and 45% asthma breakthrough despite medication. CONCLUSIONS: The ALMA tool is useful as a follow-up instrument in clinical practice to structure patient visits and assess asthma treatment in primary care. The breadth of the questions and the pragmatic use in clinical practice also make it useful as an outcome measure

Interpretation of the breath hydrogen profile obtained after ingesting a solid meal containing unabsorbable carbohydrate.

The extent to which monitoring breath hydrogen excretion provides information concerning the entry of the residues of a solid test meal into the colon was investigated in 89 normal subjects, and 11 patients with the irritable bowel syndrome. The profile of breath hydrogen concentration showed an early peak, that occurred soon after ingesting the test meal in 89% subjects. This was followed by a later more prolonged rise in breath hydrogen concentration. The early peak occurred well before a radioactive marker, incorporated in the test meal, reached the caecum and the data suggest it was predominantly caused by the emptying of the remnants of the previous meal from the ileum into the colon. This hypothesis was supported by direct measurements of the rate of delivery of ileostomy effluent in 12 subjects with terminal ileostomies. Fermentation of carbohydrate in the mouth may, however, contribute to the initial peak, but this contribution may be avoided by collecting gas samples from the nares. The secondary rise in breath hydrogen excretion was closely correlated with the arrival of the radioactive marker in the caecum (r = 0.91), p less than 0.001), though the time, at which the secondary peak of breath hydrogen excretion occurred was poorly correlated with the time that all the radioactive test meal had entered the colon. When lactulose was infused directly into the colon, as little as 0.5 g produced a discernible hydrogen response, which occurred within two minutes of the infusion. Increasing the rate of colonic infusion of a 50 ml solution of 10% lactulose from 0.02 to 0.15 g/min in five subjects significantly increased the breath hydrogen concentration. At infusion rates below 0.075 g lactulose/minute, the peak breath hydrogen response preceded the end ot the infusion, while at higher rates of infusion, the peak hydrogen response occurred after the end of the infusion. Although these results confirmed that monitoring breath hydrogen concentration usefully signalled the time taken for a meal containing unabsorbed carbohydrate to reach the colon, it did not reliably indicate the time when all of the meal had entered the colon. Finally, the use of the maximum increase in breath hydrogen concentration as an index of the degree of carbohydrate malabsorption assumes uniform rates of entry into the colon