Using a mobile application to reduce potentially inappropriate prescribing for older Brazilian adults in primary care: a triple-blind randomised clinical trial.

BACKGOUND: Potentially inappropriate prescribing (PIP) has been evaluated in several countries, and several strategies have been devised for deprescribing drugs in older adults. The aim of this study was to evaluate the efficacy of a mobile application in reducing PIP for older adults in primary care facilities in Brazil. METHODS: This randomised, triple-blind, parallel-group trial was conducted in 22 public primary care facilities in Brazil. During the intervention phase, the general practitioners (GPs) were randomly allocated to the intervention (MPI Brasil app provides information about PIP, therapeutic alternatives and deprescribing) or control (MedSUS app provides general information about medications) group. All GPs were trained on the Clinical Decision-Making Process and how to access an Evidence-Based Health website. The GPs received an Android tablet with an installed mobile application depending on their allocated group, which they used when caring for older patients over at least 3 months. At the end of this period, a sample of older patients aged ≥ 60 years who had been awaiting medical consultation by the participating GPs were interviewed and their prescriptions analysed. The primary outcome was the frequency of PIP in and between the groups. RESULTS: Among 53 GPs who were administered the baseline survey, 14 were included in the clinical trial. At baseline, 146 prescriptions were analysed: the PIP overall was 37.7% (55/146), in the intervention group was 40.6% (28/69), and in the control group was 35.1% (27/77). After the intervention, 284 prescriptions were analysed: the PIP overall was 31.7% (90/284), in the intervention group was 32.2% (46/143), and in the control group was 31.2% (44/141) (RR: 1.16; 95% CI, 0.76-1.76). In the within-group analysis, the PIP reduced from before to after the intervention in both groups-more significantly in the intervention than in the control group (p < 0.001). In the stratified analysis of PIP frequency by GPs, there was a relative risk reduction in 86% (6/7) of GPs in the intervention group compared to 71% (5/7) in the control group. CONCLUSION: We found that the MPI Brasil app effectively reduced PIP, suggesting that it may be useful to incorporate this tool into clinical practice. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT02918643). First registration on 22/09/2016.

Measuring resilience and stress during pregnancy and its relation to vulnerability and pregnancy outcomes in a nulliparous cohort study.

BACKGROUND: Resilience reflects coping with pregnancy-specific stress, including physiological adaptations of the maternal organism or factors arising from the socioeconomic context, such as low income, domestic violence, drug and alcohol use, lack of a support network and other vulnerability characteristics. Resilience is a dynamic characteristic that should be comparatively evaluated within a specific context; its association with perceived stress and social vulnerability during pregnancy is still not fully understood. This study aimed at exploring maternal resilience, perceived stress and social vulnerability during pregnancy and its associated factors and outcomes. METHODS: Prospective multicenter cohort study of nulliparous women in Brazil determining resilience (Resilience Scale; RS) and stress (Perceived Stress Scale; PSS) at 28 weeks of gestation (± 1 week). Resilience and stress scores were compared according to sociodemographic characteristics related to maternal/perinatal outcomes and social vulnerability, defined as having low level of education, being adolescent, without a partner or ethnicity other than white. RESULTS: We included 383 women who completed the RS and PSS instruments. Most women showed low resilience scores (median: 124.0; IQR 98-143). Women with a low resilience score (RS < 125) were more likely from the Northeast region, adolescents, other than whites, did not study or work, had a low level of education, low family income and received public antenatal care. Higher scores of perceived stress were shown in the Northeast, other than whites, at low levels of education, low annual family income and public antenatal care. Pregnant women with low resilience scores (n = 198) had higher perceived stress scores (median = 28) and at least one vulnerability criterion (n = 181; 91.4%). CONCLUSION: Our results reinforce the role of resilience in protecting women from vulnerability and perceived stress. It may prevent complications and build a positive experience during pregnancy.

The impact of maternal morbidity on cesarean section rates: exploring a Latin American network of sentinel facilities using the Robson's Ten Group Classification System.

BACKGROUND: Latin America has the highest Cesarean Section Rates (CSR) in the world. Robson's Ten Group Classification System (RTGCS) was developed to enable understanding the CSR in different groups of women, classified according to obstetric characteristics into one of ten groups. The size of each CS group may provide helpful data on quality of care in a determined region or setting. Data can potentially be used to compare the impact of conditions such as maternal morbidity on CSR. The objective of this study is to understand the impact of Severe Maternal Morbidity (SMM) on CSR in ten different groups of RTGCS. METHODS: Secondary analysis of childbirth information from 2018 to 2021, including 8 health facilities from 5 Latin American and Caribbean countries (Bolivia, Guatemala, Honduras, Nicaragua, and the Dominican Republic), using a surveillance database (SIP-Perinatal Information System, in Spanish) implemented in different settings across Latin America. Women were classified into one of RTGCS. The frequency of each group and its respective CSR were described. Furthermore, the sample was divided into two groups, according to maternal outcomes: women without SMM and those who experienced SMM, considering Potentially Life-threatening Conditions, Maternal Near Miss and Maternal Death as the continuum of morbidity. RESULTS: Available data were obtained from 92,688 deliveries using the Robson Classification. Overall CSR was around 38%. Group 5 was responsible for almost one-third of cesarean sections. SMM occurred in 6.7% of cases. Among these cases, the overall CSR was almost 70% in this group. Group 10 had a major role (preterm deliveries). Group 5 (previous Cesarean section) had a very high CSR within the group, regardless of the occurrence of maternal morbidity (over 80%). CONCLUSION: Cesarean section rate was higher in women experiencing SMM than in those without SMM in Latin America. SMM was associated with higher Cesarean section rates, especially in groups 1 and 3. Nevertheless, group 5 was the major contributor to the overall CSR.

Ketamine-dexmedetomidine combination for sedation in pediatric major surgery in a low-income country.

Anorectal malformations are one of the most frequent congenital malformations treated by pediatric surgeons. In low-income countries, the surgical and anesthetic management of children in need of these procedures can be challenging. Limited oxygen supply, lack of equipment, especially pediatric, and intensive care units make the use of regional anesthesia appealing. We present a series of four cases of anorectal malformations corrections in Guinea Bissau, in children up to 13 months of age, under regional anesthesia and sedation with ketodex, a mixture of ketamine and dexmedetomidine (in a proportion of 1 mg to 1 µg). No child developed respiratory depression requiring airway intervention or supplemental oxygen, or had hemodynamic instability.

Association between cervical length and gestational age at birth in singleton pregnancies: a multicentric prospective cohort study in the Brazilian population.

BACKGROUND: Short cervical length measured during the second trimester of pregnancy is an important risk factor for spontaneous preterm birth (sPTB). The aim of this study is to identify the association between mid-pregnancy cervical length (CL) and gestational age at birth in asymptomatic singleton pregnant women. METHODS: This is a prospective cohort study involving singleton pregnant women who participated in the screening phase of a Brazilian multicenter randomized controlled trial (P5 trial) between July 2015 and March 2019. Transvaginal ultrasound to measure CL was performed from 18 to 22 + 6 weeks. Women with CL ≤ 30 mm received vaginal progesterone (200 mg/day) until 36 weeks' gestation. For this analysis we considered all women with CL ≤ 30 mm receiving progesterone and a random selection of women with CL > 30 mm, keeping the populational distribution of CL. We obtained prognostic effectiveness data (area under receive operating characteristic curve (AUC), sensitivity and specificity and estimated Kaplan-Meier curves for preterm birth using different CL cutoff points. RESULTS: We report on 3139 women and identified a negative association between cervical length and sPTB. CL ≤ 25 mm was associated with sPTB < 28, sPTB < 34 and sPTB < 37 weeks, whereas a CL 25-30 mm was directly associated with late sPTB. CL by transvaginal ultrasound presented an AUC of 0.82 to predict sPTB < 28 weeks and 0.67 for sPTB < 34 weeks. Almost half of the sPTB occurred in nulliparous women and CL ≤ 30 mm was associated with sPTB at < 37 weeks (OR = 7.84; 95%CI = 5.5-11.1). The number needed to screen to detect one sPTB < 34 weeks in women with CL ≤ 25 mm is 121 and we estimated that 248 screening tests are necessary to prevent one sPTB < 34 weeks using progesterone prophylaxis. CONCLUSIONS: CL measured by transvaginal ultrasound should be used to predict sPTB < 34 weeks. Women with CL ≤ 30 mm are at increased risk for late sPTB.

Genomic Surveillance of Yellow Fever Virus Epizootic in São Paulo, Brazil, 2016 - 2018.

São Paulo, a densely inhabited state in southeast Brazil that contains the fourth most populated city in the world, recently experienced its largest yellow fever virus (YFV) outbreak in decades. YFV does not normally circulate extensively in São Paulo, so most people were unvaccinated when the outbreak began. Surveillance in non-human primates (NHPs) is important for determining the magnitude and geographic extent of an epizootic, thereby helping to evaluate the risk of YFV spillover to humans. Data from infected NHPs can give more accurate insights into YFV spread than when using data from human cases alone. To contextualise human cases, identify epizootic foci and uncover the rate and direction of YFV spread in São Paulo, we generated and analysed virus genomic data and epizootic case data from NHPs in São Paulo. We report the occurrence of three spatiotemporally distinct phases of the outbreak in São Paulo prior to February 2018. We generated 51 new virus genomes from YFV positive cases identified in 23 different municipalities in São Paulo, mostly sampled from NHPs between October 2016 and January 2018. Although we observe substantial heterogeneity in lineage dispersal velocities between phylogenetic branches, continuous phylogeographic analyses of generated YFV genomes suggest that YFV lineages spread in São Paulo at a mean rate of approximately 1km per day during all phases of the outbreak. Viral lineages from the first epizootic phase in northern São Paulo subsequently dispersed towards the south of the state to cause the second and third epizootic phases there. This alters our understanding of how YFV was introduced into the densely populated south of São Paulo state. Our results shed light on the sylvatic transmission of YFV in highly fragmented forested regions in São Paulo state and highlight the importance of continued surveillance of zoonotic pathogens in sentinel species.

Performances of birthweight charts to predict adverse perinatal outcomes related to SGA in a cohort of nulliparas.

BACKGROUND: Small-for-gestational-age neonates (SGA) are at increased risk of neonatal morbidity. Nulliparity represents a risk factor for SGA; birthweight charts may perform differently for the detection of SGA among nulliparas. This study aimed at describing the prevalence of SGA in nulliparas according to different birthweight charts and evaluating the diagnostic performance of these charts to maternal and perinatal outcomes. METHODS: This is a secondary analysis of a Brazilian cohort of nulliparas named Preterm SAMBA study. Birthweight centiles were calculated using the Intergrowth-21st, WHO-Fetal Growth Charts, Birth in Brazil population chart and GROW-customised chart. The risks of outcomes among SGA neonates and their mothers in comparison to neonates with birthweights between the 40th-60th centiles were calculated, according to each chart. ROC curves were used to detect neonatal morbidity in neonates with birth weights below different cutoff centiles for each chart. RESULTS: A sample of 997 nulliparas was assessed. The rate of SGA infants varied between 7.0-11.6%. All charts showed a significantly lower risk of caesarean sections in women delivering SGA neonates compared to those delivering adequate-for-gestational-age neonates (OR 0.55-0.64, p < .05). The charts had poor performance (AUC 0.492 - 0.522) for the detection of neonatal morbidity related to SGA born at term. CONCLUSION: The populational and customised birthweight charts detected different prevalence of small-for-gestational-age neonates and showed similar and poor performance to identify related neonatal adverse outcomes in this population.

Differential Yellow Fever Susceptibility in New World Nonhuman Primates, Comparison with Humans, and Implications for Surveillance.

A major outbreak of yellow fever (YF) occurred in Brazil during 2016-2018. Epizootics in New World nonhuman primates are sentinel events for YF virus circulation. However, genus-specific susceptibilities and suitability for YF surveillance remain poorly understood. We obtained and compared epidemiologic, histopathologic, immunohistochemical, and molecular results from 93 human and 1,752 primate cases submitted during the recent YF outbreak in Brazil (2017), with the support of the Brazilian National YF Surveillance Program. We detected heterogeneous YF-associated profiles among the various genera of primates we analyzed. Alouatta primates were the most reliable sentinel; Sapajus and Callicebus primates had higher viral loads but lower proportional mortality rates. Callithrix primates were the least sensitive, showing lower viral loads, lower proportional mortality rates, and no demonstrable YF virus antigen or extensive lesions in liver, despite detectable viral RNA. These differences in susceptibility, viral load, and mortality rates should be considered in strategic surveillance of epizootics and control measures for YF.

Long-Term Consequences of Severe Maternal Morbidity on Infant Growth and Development.

OBJECTIVE: Severe maternal morbidity (SMM) is already known to be associated with adverse neonatal outcomes, however, its association with long-term deficits of weight and height, and impairment in neurodevelopment among children was not yet fully assessed. We aim to evaluate whether SMM has repercussions on the weight and height-for-age and neurodevelopmental status of the child. METHODS: A retrospective cohort analysis with women who had SMM events in a tertiary referral center in Brazil. They were compared to a control group of women who had not experienced any SMM. Childbirth and perinatal characteristics, weight and height-for-age deficits and neurodevelopmental impairment suspicion by Denver II Test were comparatively assessed in both groups using RR and 95% CI. Multiple regression analysis was used addressing deficit of weight-for-age, height-for-age and an altered Denver Test, estimating their independent adjusted RR and 95% CI. RESULTS: 634 women with perinatal outcomes available (311 with SMM and 323 without) and 571 children were assessed. Among women with SMM, increased rates in perinatal deaths, Apgar lower than 7 at five minutes, shorter breastfeeding period, preterm birth (49.0% × 11.1%), low birthweight (45.8% × 11.5%), deficits of weight-for-age [RR 3.11 (1.60-6.04)] and height-for-age [RR 1.52 (1.06-2.19)] and altered Denver Test [RR 1.5 (1.02-2.36)] were more frequently found than in the control group. SMM was not identified as independently associated with any of the main outcomes. CONCLUSION: SMM showed to be associated with a negative impact on growth and neurodevelopment aspects of perinatal and infant health. These findings suggest that effective health policies directed towards appropriate care of pregnancy may have an impact on the reduction of maternal, neonatal and infant morbidity and mortality.

COVID-19 and inequities in the Americas: lessons learned and implications for essential health services.

The COVID-19 pandemic has exacerbated social, economic, and health-related disparities, which disproportionately affect persons living in conditions of vulnerability. Such populations include ethnic groups who face discrimination and experience barriers to accessing comprehensive health care. The COVID-19 pandemic has exposed these health disparities, and disruptions of essential health services have further widened the gaps in access to health care. Noncommunicable diseases are more prevalent among groups most impacted by poor social determinants of health and have been associated with an increased likelihood of severe COVID-19 disease and higher mortality. Disruptions in the provision of essential health services for noncommunicable diseases, mental health, communicable diseases such as HIV, tuberculosis, and malaria, and maternal and child health services (including sexual and reproductive health), are projected to also increase poor health outcomes. Other challenges have been an increased frequency of interpersonal violence and food insecurity. Countries in the Americas have responded to the disruptions caused by the pandemic by means of health service delivery through telemedicine and other digital solutions and stepping up social service support interventions. As vaccinations for COVID-19 create the opportunity to overcome the pandemic, countries must strengthen primary health care and essential health services with a view to ensuring equity, if the region is to achieve universal health coverage in fulfillment of the Sustainable Development Goals.

La pandemia de COVID-19 ha acentuado las desigualdades sociales, económicas y relacionadas con la salud, que afectan desproporcionadamente a las personas en situación de vulnerabilidad. Esta población incluye grupos étnicos que se enfrentan a la discriminación y obstáculos para el acceso a la atención integral de salud. La pandemia de COVID-19 ha expuesto estas desigualdades de salud, y las interrupciones de los servicios esenciales de salud han ampliado aún más las brechas en el acceso a la atención de salud. Las enfermedades no transmisibles son más prevalentes en los grupos que han sufrido un mayor impacto de los determinantes sociales de la salud deficientes y se han asociado con una mayor probabilidad de presentar un cuadro grave de COVID-19 y una mayor mortalidad. Asimismo, se proyecta que las interrupciones en la prestación de servicios esenciales de salud para las enfermedades no transmisibles, la salud mental, las enfermedades transmisibles como la infección por el VIH, la tuberculosis y la malaria, y los servicios de salud maternoinfantil (como la salud sexual y reproductiva) incrementen los resultados deficientes en materia de salud. Otros retos son una mayor frecuencia de la violencia interpersonal y la inseguridad alimentaria. Los países de la Región de las Américas han respondido a las interrupciones causadas por la pandemia con la prestación de servicios de salud mediante la telemedicina y otras soluciones digitales, y la aceleración de las intervenciones de apoyo de los servicios sociales. A medida que la vacunación contra la COVID-19 crea la oportunidad de superar la pandemia, los países deben fortalecer su atención primaria de salud y sus servicios de salud esenciales a fin de garantizar la equidad, para que la Región logre la cobertura universal de salud en cumplimiento de los Objetivos de Desarrollo Sostenible.

A pandemia de COVID-19 exacerbou as disparidades sociais, econômicas e as relacionadas à saúde, que afetam de maneira desproporcional as pessoas que vivem em situação de vulnerabilidade. Essas populações incluem grupos étnicos que enfrentam discriminação e barreiras para o acesso à atenção integral à saúde. A pandemia de COVID-19 expôs essas disparidades, e as interrupções nos serviços essenciais de saúde ampliaram ainda mais as lacunas no acesso aos cuidados de saúde. As doenças não transmissíveis são mais prevalentes entre os grupos mais afetados por determinantes sociais da saúde deficientes e estão associadas a um aumento na probabilidade de doença grave pela COVID-19 e mortalidade mais elevada. Prevê-se que as interrupções na prestação de serviços essenciais de saúde para doenças não transmissíveis, saúde mental, doenças transmissíveis como HIV, tuberculose e malária, bem como dos serviços de saúde materno-infantil (incluindo saúde sexual e reprodutiva) também aumentem os desfechos adversos de saúde. Outros desafios são o aumento da frequência da violência interpessoal e insegurança alimentar. Os países das Américas responderam às interrupções causadas pela pandemia com a prestação de serviços de saúde por meio da telemedicina e outras soluções digitais, e a aceleração de intervenções de apoio dos serviços sociais. À medida em que a vacinação contra a COVID-19 oferece a oportunidade de superar a pandemia, os países devem fortalecer a atenção primária à saúde e os serviços essenciais de saúde com o objetivo de garantir a equidade, para que a região atinja a cobertura universal de saúde em cumprimento aos Objetivos de Desenvolvimento Sustentável.

Improving Seismic Inversion Robustness via Deformed Jackson Gaussian.

The seismic data inversion from observations contaminated by spurious measures (outliers) remains a significant challenge for the industrial and scientific communities. This difficulty is due to slow processing work to mitigate the influence of the outliers. In this work, we introduce a robust formulation to mitigate the influence of spurious measurements in the seismic inversion process. In this regard, we put forth an outlier-resistant seismic inversion methodology for model estimation based on the deformed Jackson Gaussian distribution. To demonstrate the effectiveness of our proposal, we investigated a classic geophysical data-inverse problem in three different scenarios: (i) in the first one, we analyzed the sensitivity of the seismic inversion to incorrect seismic sources; (ii) in the second one, we considered a dataset polluted by Gaussian errors with different noise intensities; and (iii) in the last one we considered a dataset contaminated by many outliers. The results reveal that the deformed Jackson Gaussian outperforms the classical approach, which is based on the standard Gaussian distribution.

Building a Digital Tool for the Adoption of the World Health Organization's Antenatal Care Recommendations: Methodological Intersection of Evidence, Clinical Logic, and Digital Technology.

BACKGROUND: One of the key mandates of the World Health Organization (WHO) is to develop guidelines, defined as "a document containing recommendations for clinical practice or public health policy." Guidelines represent the global standard for information sources shaping clinical practice and public health policies. Despite the rigorous development process and the value of guidelines for setting standards, implementing such standards within local contexts and at the point of care is a well-documented challenge. Digital technologies enable agile information management and may facilitate the adaptation of guidelines to diverse settings of health services delivery. OBJECTIVE: The objective of this paper is to detail the systematic and iterative process involved in transforming the WHO Antenatal Care (ANC) guidelines into a digital decision-support and patient-record application for routine use in primary health care settings, known as the WHO digital ANC module. METHODS: The WHO convened a team of clinical and digital health experts to develop the WHO digital ANC module as a tool to assist health care professionals in the implementation of WHO evidence-based recommendations for pregnant women. The WHO digital ANC module's creation included the following steps: defining a minimum viable product (MVP), developing clinical workflows and algorithms, algorithm testing, developing a data dictionary, and the creation of a user interface or application development. The overall process of development took approximately 1 year to reach a stable prototype and to finalize the underlying content requirements of the data dictionary and decision support algorithms. RESULTS: The first output is a reference software reflecting the generic WHO ANC guideline content, known as the WHO digital ANC module. Within it, all actionable ANC recommendations have related data fields and algorithms to confirm whether the associated task was performed. WHO recommendations that are not carried out by the health care worker are saved as pending tasks on a woman's health record, and those that are adequately fulfilled trigger messages with positive reinforcement. The second output consists of the structured documentation of the different components which contributed to the development of the WHO digital ANC module, such as the data dictionary and clinical decision support workflows. CONCLUSIONS: This is a novel approach to facilitate the adoption and adaptation of recommendations through digital systems at the health service delivery level. It is expected that the WHO digital ANC module will support the implementation of evidence-based practices and provide information for monitoring and surveillance; however, further evidence is needed to understand how the WHO digital ANC module impacts the implementation of WHO recommendations. Further, the module's implementation will inform the WHO's ongoing efforts to create a pathway to adaptive and integrated (Smart) Guidelines in Digital Systems to improve health system quality, coverage, and accountability.

Correction: Building a Digital Tool for the Adoption of the World Health Organization's Antenatal Care Recommendations: Methodological Intersection of Evidence, Clinical Logic, and Digital Technology.

[This corrects the article DOI: 10.2196/16355.].

Prediction of Severe Maternal Outcome Among Pregnant and Puerperal Women in Obstetric ICU.

OBJECTIVE: World Health Organization recommends the use of maternal near miss as a tool to monitor and improve quality of obstetric care. Severe maternal outcome corresponds to the sum of maternal near miss and maternal death cases. This study was aimed at validating Acute Physiology and Chronic Health Evaluation II and IV, Simplified Acute Physiology Score III, and Sequential Organ Failure Assessment in pregnant and postpartum women in predicting severe maternal outcome. DESIGN: A retrospective cohort study. SETTING: Obstetric ICU in a tertiary care hospital in Brazil. PATIENTS: Pregnant and postpartum women admitted to the obstetric ICU during a 3-year period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 279 women were admitted to ICU, an admission rate of 34.6/1,000 live births, and the mortality index to severe maternal outcome (maternal death/maternal near miss + maternal death) was 7.7%. Total Sequential Organ Failure Assessment had a better overall performance than remaining scores for total hospitalizations (area under the curve, 0.86; standardized mortality ratio, 0.96; 95% CI, 0.74-1.22), for hypertensive direct causes (area under the curve, 0.81; standardized mortality ratio, 0.73; 95% CI, 0.31-1.43), and indirect causes (area under the curve, 0.89; standardized mortality ratio, 0.85; 95% CI, 0.59-1.19). The Acute Physiology and Chronic Health Evaluation II had a better overall performance than total Sequential Organ Failure Assessment for hemorrhagic causes (area under the curve, 0.75; standardized mortality ratio, 1.0; 95% CI, 0.61-1.54). CONCLUSIONS: Total Sequential Organ Failure Assessment may be used to predict severe maternal outcome in obstetric populations admitted to ICU. The Acute Physiology and Chronic Health Evaluation II may be applied to predict severe maternal outcome in hemorrhagic complications. We do not recommend Acute Physiology and Chronic Health Evaluation IV and Simplified Acute Physiology Score III for the prediction of severe maternal outcome.

Probing the Formation of Wormlike Micelles Formed by Cationic Surfactant with Chlorobenzoate Derivatives.

The energy released when tetradecyltrimethylammonium bromide (C14TAB) is combined with different derivatives of chlorobenzoates in an isothermal titration calorimeter (ITC) allows a direct evaluation of the spontaneity of the threading of the aromatic anions into the micellar palisade. The comparison between the enthalpimetric curves with the ones for viscosity of the solutions, hydrodynamic radii of the aggregates (dynamic light scattering experiments), and the fraction of aromatic anions incorporated (diffusion-ordered spectroscopy experiments) allows the establishment of the variations of enthalpy with formation, growth, and decrease of the wormlike micelles (WLMs). The formation of WLMs with C14TAB is very favored (very exothermic) for titrations of chlorobenzoate derivatives which present the chlorine atom in positions 3 or 4 of the aromatic ring. However, the aggregation is highly unfavorable if chlorine is at position 2 of chlorobenzoate. According to the results, the high potential of the ITC to determine critical concentrations and the energies associated with the aggregation of a cationic surfactant and aromatic anions for the formation of WLMs was demonstrated.

Mean arterial blood pressure: potential predictive tool for preeclampsia in a cohort of healthy nulliparous pregnant women.

BACKGROUND: Prediction of preeclampsia is a challenge to overcome. The vast majority of prospective studies in large general obstetric populations have failed in the purpose of obtain a useful and effective model of prediction, sometimes based on complex tools unavaible in areas where the incidence of preeclampsia is the highest. The goal of this study was to assess mean arterial blood pressure (MAP) levels at 19-21, 27-29 and 37-39 weeks of gestation and performance of screening by MAP for the prediction of preeclampsia in a Brazilian cohort of healthy nulliparous pregnant women. METHODS: This was a cohort approach to a secondary analysis of the Preterm SAMBA study. Mean arterial blood pressure was evaluated at three different time periods during pregnancy. Groups with early-onset preeclampsia, late-onset preeclampsia and normotension were compared. Increments in mean arterial blood pressure between 20 and 27 weeks and 20 and 37 weeks of gestation were also calculated for the three groups studied. The accuracy of mean arterial blood pressure in the prediction of preeclampsia was determined by ROC curves. RESULTS: Of the 1373 participants enrolled, complete data were available for 1165. The incidence of preeclampsia was 7.5%. Women with early-onset preeclampsia had higher mean arterial blood pressure levels at 20 weeks of gestation, compared to the normotensive group. Women with late-onset preeclampsia had higher mean arterial blood pressure levels at 37 weeks of gestation, than the normotensive groups and higher increases in this marker between 20 and 37 weeks of gestation. Based on ROC curves, the predictive performance of mean arterial blood pressure was higher at 37 weeks of gestation, with an area under the curve of 0.771. CONCLUSION: As an isolated marker for the prediction of preeclampsia, the performance of mean arterial blood pressure was low in a healthy nulliparous pregnant women group. Considering that early-onset preeclampsia cases had higher mean arterial blood pressure levels at 20 weeks of gestation, future studies with larger cohorts that combine multiple markers are needed for the development of a preeclampsia prediction model.

Reference ranges for ultrasound measurements of fetal kidneys in a cohort of low-risk pregnant women.

PURPOSE: Alterations in renal dimensions may be an early manifestation of deviation from normality, with possible repercussions beyond intrauterine life. The objective of this study was to establish reference curves for fetal kidney dimensions and volume from 14 to 40 weeks of gestation. METHODS: This is a prospective longitudinal study of 115 Brazilian participants in the "WHO multicentre study for the development of growth standards from fetal life to childhood: the fetal component". Pregnant women with clinical and sociodemographic characteristics allowing the full potential fetal growth were followed up from the first trimester until delivery. These women underwent serial sonographic evaluation of fetal kidneys. The longitudinal, anteroposterior and transverse diameters of both fetal kidneys were measured, in addition to calculation of kidney volume. By quantile regression analysis, reference curves of renal measurements related to gestational age were built. RESULTS: Standard normal sonographic values of renal biometry were defined during pregnancy. Reference values for the 10th, 50th and 90th centiles of different fetal kidney measurements (longitudinal, anteroposterior, transverse and volume) from the 14th to the 40th week of gestation were fitted. CONCLUSION: The reference curves presented should be of the utmost importance for screening and diagnosis of alterations in renal development during the intrauterine period.

Heart rate variability, salivary cortisol and competitive state anxiety responses during pre-competition and pre-training moments.

The study aimed to investigate physiological and psychological states prior to competition and prior to training in three different demanding activities. Eighteen canoe athletes, 18 street runners and 18 jiu-jitsu fighters were included in this study (n=54). The Competitive State Anxiety Inventory-2 (CSAI-2), salivary cortisol and heart rate variability (HRV) were measured at two time points (pre-training and pre-competition). Somatic anxiety (F1,42 = 15.29, p = 0.0003), HRV (F1,42 = 23.24, p < 0.0001) and salivary cortisol (F1,42 = 22.96, p < 0.0001) were significantly greater at the pre-competition measurement point than at the pre-training point, but without a main effect of the type of athlete on these variables. A main effect of the type of athlete was found on somatic anxiety (F2,42 = 6.58, p = 0.0033), cognitive anxiety (F2,42 = 10.69, p = 0.0002) and self-confidence (F2,42 = 5.42, p = 0.0080). Correlations between most CSAI-2 and physiological parameters were not significant (p > 0.05). In conclusion, the results indicated that both emotional indices and psychophysiological indices of stress are higher before competition than before training, with differences between emotional states between these sports. Although correlations between emotional states and psycho-physiological states before competition and before training were largely non-significant, these findings reinforce the importance of psychological monitoring of athletes in association with traditional physiological markers such as cortisol and HRV in sportive training programmes as complementary resources to improve both competition performance and the training routine.

Perinatal outcomes in twin pregnancies complicated by maternal morbidity: evidence from the WHO Multicountry Survey on Maternal and Newborn Health.

BACKGROUND: Twin pregnancy was associated with significantly higher rates of adverse neonatal and perinatal outcomes, especially for the second twin. In addition, the maternal complications (potentially life-threatening conditions-PLTC, maternal near miss-MNM, and maternal mortality-MM) are directly related to twin pregnancy and independently associated with adverse perinatal outcome. The objective of the preset study is to evaluate perinatal outcomes associated with twin pregnancies, stratified by severe maternal morbidity and order of birth. METHODS: Secondary analysis of the WHO Multicountry Survey on Maternal and Newborn Health (WHOMCS), a cross-sectional study implemented in 29 countries. Data from 8568 twin deliveries were compared with 308,127 singleton deliveries. The occurrence of adverse perinatal outcomes and maternal complications were assessed. Factors independently associated with adverse perinatal outcomes were reported with adjusted PR (Prevalence Ratio) and 95%CI. RESULTS: The occurrence of severe maternal morbidity and maternal death was significantly higher among twin compared to singleton pregnancies in all regions. Twin deliveries were associated with higher rates of preterm delivery (37.1%), Apgar scores less than 7 at 5th minute (7.8 and 10.1% respectively for first and second twins), low birth weight (53.2% for the first and 61.1% for the second twin), stillbirth (3.6% for the first and 5.7% for the second twin), early neonatal death (3.5% for the first and 5.2% for the second twin), admission to NICU (23.6% for the first and 29.3% for the second twin) and any adverse perinatal outcomes (67% for the first twin and 72.3% for the second). Outcomes were consistently worse for the second twin across all outcomes. Poisson multiple regression analysis identified several factors independently associated with an adverse perinatal outcome, including both maternal complications and twin pregnancy. CONCLUSION: Twin pregnancy is significantly associated with severe maternal morbidity and with worse perinatal outcomes, especially for the second twin.

Simple protocol for population (Sanger) sequencing for Zika virus genomic regions.

BACKGROUND: A number of Zika virus (ZIKV) sequences were obtained using Next-generation sequencing (NGS), a methodology widely applied in genetic diversity studies and virome discovery. However Sanger method is still a robust, affordable, rapid and specific tool to obtain valuable sequences. OBJECTIVE: The aim of this study was to develop a simple and robust Sanger sequencing protocol targeting ZIKV relevant genetic regions, as envelope protein and nonstructural protein 5 (NS5). In addition, phylogenetic analysis of the ZIKV strains obtained using the present protocol and their comparison with previously published NGS sequences were also carried out. METHODS: Six Vero cells isolates from serum and one urine sample were available to develop the procedure. Primer sets were designed in order to conduct a nested RT-PCR and a Sanger sequencing protocols. Bayesian analysis was used to infer phylogenetic relationships. FINDINGS: Seven complete ZIKV envelope protein (1,571 kb) and six partial NS5 (0,798 Kb) were obtained using the protocol, with no amplification of NS5 gene from urine sample. Two NS5 sequences presented ambiguities at positions 495 and 196. Nucleotide analysis of a Sanger sequence and consensus sequence of previously NGS study revealed 100% identity. ZIKV strains described here clustered within the Asian lineage. MAIN CONCLUSIONS: The present study provided a simple and low-cost Sanger protocol to sequence relevant genes of the ZIKV genome. The identity of Sanger generated sequences with published consensus NGS support the use of Sanger method for ZIKV population studies. The regions evaluated were able to provide robust phylogenetic signals and may be used to conduct molecular epidemiological studies and monitor viral evolution.