Impact of meningococcal C conjugate vaccine on incidence of invasive meningococcal disease in an 18-year time series in Brazil and in distinct Brazilian regions.

OBJECTIVE: To evaluate the impact of meningococcal C conjugate (MCC) vaccine in Brazil. METHODS: Ecological study assessing all invasive meningococcal disease (IMD) and meningococcal C disease (MenC) cases reported in all age groups, from 2001 to 2019. MCC was implemented in 2010. Data were collected on the DATASUS platform. Joinpoint regression was performed to assess the annual percent change (APC) of the incidence rate. RESULTS: Invasive meningococcal disease incidence decreased in all Brazilian regions from 2001 onwards, without apparent additional reduction attributable to MCC vaccine in the North, Northeast and South. The higher and statistically significant APC reduction in all age groups, in the North and South, and in children <5 years, in the Northeast, occurred between 2001 and 2011 (-15.4%), 2004 and 2012 (-14.4%), and 2001 and 2013 (-10.3%), respectively, before MCC vaccine implementation. Annual incidence of MenC in children under 5 years significantly fell in the North (-6.8%; 2011-2018), Southeast (-40.6%; 2010-2015) and Midwest (-48.6%; 2010-2014), which may be attributable to MCC implementation. CONCLUSION: Invasive meningococcal disease and MenC behaved differently after MCC vaccine implementation in Brazil during this 18-year time-series analysis. This suggests that the control of IMD should be based on multiple public health care measures and considered on a regional basis.

Differentiation of COVID-19 signs and symptoms from allergic rhinitis and common cold: An ARIA-EAACI-GA2 LEN consensus.

BACKGROUND: Although there are many asymptomatic patients, one of the problems of COVID-19 is early recognition of the disease. COVID-19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID-19 symptoms may be mistaken with the common cold or allergic rhinitis. An ARIA-EAACI study group attempted to differentiate upper respiratory symptoms between the three diseases. METHODS: A modified Delphi process was used. The ARIA members who were seeing COVID-19 patients were asked to fill in a questionnaire on the upper airway symptoms of COVID-19, common cold and allergic rhinitis. RESULTS: Among the 192 ARIA members who were invited to respond to the questionnaire, 89 responded and 87 questionnaires were analysed. The consensus was then reported. A two-way ANOVA revealed significant differences in the symptom intensity between the three diseases (p < .001). CONCLUSIONS: This modified Delphi approach enabled the differentiation of upper respiratory symptoms between COVID-19, the common cold and allergic rhinitis. An electronic algorithm will be devised using the questionnaire.

Management of anaphylaxis due to COVID-19 vaccines in the elderly.

Older adults, especially men and/or those with diabetes, hypertension, and/or obesity, are prone to severe COVID-19. In some countries, older adults, particularly those residing in nursing homes, have been prioritized to receive COVID-19 vaccines due to high risk of death. In very rare instances, the COVID-19 vaccines can induce anaphylaxis, and the management of anaphylaxis in older people should be considered carefully. An ARIA-EAACI-EuGMS (Allergic Rhinitis and its Impact on Asthma, European Academy of Allergy and Clinical Immunology, and European Geriatric Medicine Society) Working Group has proposed some recommendations for older adults receiving the COVID-19 vaccines. Anaphylaxis to COVID-19 vaccines is extremely rare (from 1 per 100,000 to 5 per million injections). Symptoms are similar in younger and older adults but they tend to be more severe in the older patients. Adrenaline is the mainstay treatment and should be readily available. A flowchart is proposed to manage anaphylaxis in the older patients.

Adding guidance to deliberate reflection improves medical student's diagnostic accuracy.

CONTEXT: Diagnostic competence in students is a major medical education goal. Adding instructional guidelines to prompt deliberate reflection fosters medical students' diagnostic proficiency. This study investigates the effects of this teaching strategy on diagnostic accuracy in solving clinical cases of different complexity levels by novice and senior students. METHOD: Eighty third-year and 62 sixth-year medical students participated in this three-phase experimental study. First, participants were randomly assigned to one of three experimental conditions (free reflection, cued reflection and worked example) to diagnose 12 clinical text-based cases, following different levels of deliberate reflection. In an immediate test and a delayed test, the participants diagnosed varied sets of 12 cases, six involving the same diseases (four routine and two rare). The main outcomes were the diagnostic accuracy scores achieved for the cases assessed by repeated measures of analysis of variance for each category. RESULTS: There was a significant primary effect of experimental condition (P < .001), year of training (P < .001) and study phase (P < .001) on the diagnostic accuracy achieved. The use of deliberate reflection in addition to instructional guidelines resulted in improved results in the immediate test for all cases evaluated (P < .001), regardless of participants' seniority. In the delayed test, this benefit was maintained for simple cases (P < .001). For complex cases, the benefit was maintained only for senior students (P < .001). The cued reflection and worked example groups did not differ in performance (P > .05), but both groups surpassed the free reflection group (P < .001), regardless of the students' learning stage and case complexity.

Childhood asthma in low and middle-income countries: Where are we now?

Pediatric asthma has been increasing in LMICs (Low Middle-Income Countries), leading to an important burden for both children and national health systems. Implementing measures to achieve control are influenced by the degree of organization health systems have, the availability and affordability of essential asthma medications, and the effective implementation of asthma programs and asthma guidelines. In this review authors give an updated view of the current situation of these components of asthma management in LMICs.

Electronic Clinical Decision Support System for allergic rhinitis management: MASK e-CDSS.

BACKGROUND: Allergic rhinitis (AR) management has changed in recent years following the switch from the concept of disease severity to the concept of disease control, publication of the AR clinical decision support system (CDSS) and development of mobile health (m-health) tools for patients (eg Allergy Diary). The Allergy Diary Companion app for healthcare providers is currently being developed and will be launched in 2018. It incorporates the AR CDSS to provide evidence-based treatment recommendations, linking all key stakeholders in AR management. OBJECTIVE: To produce an electronic version of the AR CDSS (e-CDSS) for incorporation into the Allergy Diary Companion, to describe the app interfaces used to collect information necessary to inform the e-CDSS and to summarize some key features of the Allergy Diary Companion. METHODS: The steps involved in producing the e-CDSS and incorporating it into the Allergy Diary Companion were (a) generation of treatment management scenarios; (b) expert consensus on treatment recommendations; (c) generation of electronic decisional algorithms to describe all AR CDSS scenarios; (d) digitization of these algorithms to form the e-CDSS; and (e) embedding the e-CDSS into the app to permit easy user e-CDSS interfacing. RESULTS: Key experts in the AR field agreed on the AR CDSS approach to AR management and on specific treatment recommendations provided by Allergy Diary Companion. Based on this consensus, decision processes were developed and programmed into the Allergy Diary Companion using Titanium Appcelerator (JavaScript) for IOS tablets. To our knowledge, this is the first time the development of any m-health tool has been described in this transparent and detailed way, providing confidence, not only in the app, but also in the provided management recommendations. CONCLUSION: The Allergy Diary Companion for providers provides guideline and expert-endorsed AR management recommendations. [MASK paper No 32].

Asthma exacerbations in a subtropical area and the role of respiratory viruses: a cross-sectional study.

BACKGROUND: Multiple factors are involved in asthma exacerbations, including environmental exposure and viral infections. We aimed to assess the association between severe asthma exacerbations, acute respiratory viral infections and other potential risk factors. METHODS: Asthmatic children aged 4-14 years were enrolled for a period of 12 months and divided into two groups: those with exacerbated asthma (group 1) and non-exacerbated asthma (group 2). Clinical data were obtained and nasopharyngeal samples were collected through nasopharyngeal aspirate or swab and analysed via indirect fluorescent immunoassays to detect influenza A and B viruses, parainfluenza 1-3, adenovirus and respiratory syncytial virus. Rhinovirus was detected via molecular assays. Potential risk factors for asthma exacerbation were identified in univariate and multivariate analyses. RESULTS: In 153 children (group 1: 92; group 2: 61), median age 7 and 8 years, respectively, the rate of virus detection was 87.7%. There was no difference between groups regarding the frequency of virus detection (p = 0.68); however, group 1 showed a lower frequency (19.2%) of inhaled corticosteroid use (91.4%, p < 0.01) and evidence of inadequate disease control. In the multivariate analysis, the occurrence of three or more visits to the emergency room in the past 12 months (IRR = 1.40; p = 0.04) and nonadherence to inhaled corticosteroid (IRR = 4.87; p < 0.01) were the only factors associated with exacerbation. CONCLUSION: Our results suggest an association between asthma exacerbations, poor disease control and nonadherence to asthma medication, suggesting that viruses may not be the only culprits for asthma exacerbations in this population.

Cause-specific mortality for 249 causes in Brazil and states during 1990-2015: a systematic analysis for the global burden of disease study 2015.

BACKGROUND: Reliable data on cause of death (COD) are fundamental for planning and resource allocation priorities. We used GBD 2015 estimates to examine levels and trends for the leading causes of death in Brazil from 1990 to 2015. METHODS: We describe the main analytical approaches focused on both overall and specific causes of death for Brazil and Brazilian states. RESULTS: There was an overall improvement in life expectancy at birth from 1990 to 2015, but with important heterogeneity among states. Reduced mortality due to diarrhea, lower respiratory infections, and other infectious diseases contributed the most for increasing life expectancy in most states from the North and Northeast regions. Reduced mortality due to cardiovascular diseases was the highest contributor in the South, Southeast, and Center West regions. However, among men, intentional injuries reduced life expectancy in 17 out of 27 states. Although age-standardized rates due to ischemic heart disease (IHD) and cerebrovascular disease declined over time, these remained the leading CODs in the country and states. In contrast, leading causes of premature mortality changed substantially - e.g., diarrheal diseases moved from 1st to 13th and then the 36th position in 1990, 2005, and 2015, respectively, while violence moved from 7th to 1st and to 2nd. Overall, the total age-standardized years of life lost (YLL) rate was reduced from 1990 to 2015, bringing the burden of premature deaths closer to expected rates given the country's Socio-demographic Index (SDI). In 1990, IHD, stroke, diarrhea, neonatal preterm birth complications, road injury, and violence had ratios higher than the expected, while in 2015 only violence was higher, overall and in all states, according to the SDI. CONCLUSIONS: A widespread reduction of mortality levels occurred in Brazil from 1990 to 2015, particularly among children under 5 years old. Major shifts in mortality rates took place among communicable, maternal, neonatal, and nutritional disorders. The mortality profile has shifted to older ages with increases in non-communicable diseases as well as premature deaths due to violence. Policymakers should address health interventions accordingly.

Impulse oscillometry in the assessment of asthmatic children and adolescents: from a narrative to a systematic review.

Diagnosis and management of asthma often relies mostly on symptoms because spirometry is not always reliable in some age groups, such as preschoolers. It is unclear whether impulse oscillometry (IOS) can supplement or replace spirometry. Available reports suggest that IOS has been applied with success in asthmatic children and adolescents to assess exacerbations, level of control, severity and response to treatment in the short and long term. Very few studies using adequate sample sizes and methods have been performed comparing the accuracy of IOS to spirometry for the diagnosis of asthma. Our systematic review found only four studies that met the eligibility criteria. However, no meta-analysis was possible with the available data. Consequently, this review helps to identify research gaps involving IOS, highlighting opportunities for future studies.

Spatial distribution of tuberculosis from 2002 to 2012 in a midsize city in Brazil.

BACKGROUND: Tuberculosis (TB) remains a major public health problem in many developing countries. Exploratory spatial analysis is a powerful instrument in spatial health research by virtue of its capacity to map disease distribution and associated risk factors at the population level. The aim of the present study was to describe the epidemiologic characteristics and spatial distribution of new cases of TB reported during the period 2002-2012 in Divinopolis, a midsized city located in the state of Minas Gerais, southeastern Brazil. METHODS: Sociodemographic and clinical data relating to the study cases were retrieved from the national Brazilian database and geocoded according to residential address. Choropleth and kernel density maps were constructed and a spatial-temporal analysis was performed. Tracts defined by the 2010 national census were classified as sectors with higher or lower densities of new TB cases based on the kernel density map. Multivariate logistic analysis was used to compare the two types of sectors according to income, level of literacy and population density. RESULTS: A total of 326 new cases of TB were reported during the study period. Residential addresses relating to 309 (94.8 %) of these were available in the SINAN database and the locations were geocoded and mapped. The average incidence of TB during the study period was 14.5/100,000 inhabitants. Pulmonary TB was the most predominant form (73.6 %) and 74.5 % of patients had been cured. The percentage of cases was highest in males (67.8 %) and individuals aged 25-44 years (41.1 %), and lowest in children aged less than 15 years (4.6 %). The disease was spatially distributed throughout the urban district. The incidence rate among urban census tracts ranged from 0.06 to 1.1 %, and the disease occurred predominantly in the downtown area (99.3 %). Higher population density was associated significantly with increased odds of living in a sector with a "higher density of cases", even after adjusting for income and education (odds ratio = 13.7). CONCLUSIONS: The highest density of cases was strongly associated with higher population density but not with lower income or level of literacy.

Increased risk of allergic rhinitis among children delivered by cesarean section: a cross-sectional study nested in a birth cohort.

BACKGROUND: Few studies have evaluated the association between delivery by cesarean section (CS) and asthma, allergic rhinitis and chronic rhinitis and whether this association is different in children with and without a family history of asthma. This study aims to investigate whether children born by CS have a higher chance to develop asthma, allergic rhinitis and chronic rhinitis and to evaluate the influence of parental history of asthma on these associations. METHODS: This is a cross-sectional study of 672 children nested in a birth cohort evaluated at 6-years of age. Asthma and chronic/allergic rhinitis were identified by means of the mother's responses to the ISAAC questionnaire. The association between CS, asthma, chronic rhinitis and allergic rhinitis was evaluated by multivariable logistic regression. The evidence of effect modification of parental history of asthma on the association CS and outcomes was examined by introducing interactions terms in the logistic regression models adjusting for confounders. RESULTS: Asthma was not associated with birth by CS irrespective of parental history of asthma (odds ratio (OR) 1.03; 95 % CI 0.61-1.74). Chronic rhinitis and allergic rhinitis were both significantly associated with birth by CS but only in the subgroup of children with by parental history of asthma (OR 1.56; 95 % CI 1.04-2.34) and (OR 1.60; 95 % CI 1.01-2.55) respectively, after adjustment for confounders. The parental history of asthma was a effect modifier in the association between CS, chronic rhinitis and allergic rhinitis (p for effect modification = 0.10 and 0.02, respectively). CONCLUSION: CS increases the risk of chronic rhinitis and allergic rhinitis in children at 6 years of age with parental history of asthma. Health professionals must be alerted with regard to the increased risk of allergic rhinitis and made aware this is another reason to avoid unnecessary CS.

Phenotypes of severe asthma among children and adolescents in Brazil: a prospective study.

BACKGROUND: The morbidity associated with severe uncontrolled asthma is disproportionately higher in low- and middle-income countries than in high-income countries. The aim of this study was to describe the phenotypic characteristics of difficult-to-treat severe asthma and treatment-resistant severe asthma in a sample of children and adolescents in Brazil. METHODS: This was a prospective study, conducted between 2010 and 2014, following 61 patients (6-18 years of age) who had been diagnosed with severe uncontrolled asthma. The patients were classified and managed in accordance with the World Health Organization asthma follow-up protocol, which calls for re-evaluations of the diagnosis, level of control (functional and clinical), comorbidities, inhaler technique, and environmental factors, together with adjustment of the treatment to achieve a target level of control. We assessed pulmonary function, measured fractional exhaled nitric oxide, and performed sputum cytology. After the target rate of ≥ 80% adherence to inhaled corticosteroid treatment had been reached and all of the re-evaluations had been performed, the patients incorrectly diagnosed with severe uncontrolled asthma were excluded and the remaining patients were classified as having treatment-resistant or difficult-to-treat severe asthma. RESULTS: We found that, of the 61 patients evaluated, 10 had been misdiagnosed (i.e., they did not have asthma), 15 had moderate asthma, and 36 had severe uncontrolled asthma. Among those 36 patients, the asthma was classified as treatment-resistant in 20 (55.6%) and as difficult-to-treat in 16 (44.4%). In comparison with the patients with difficult-to-treat severe asthma, those with treatment-resistant severe asthma showed a higher median level of fractional exhaled nitric oxide (40 ppb vs. 12 ppb; P < 0.037) and a lower median forced expiratory volume in one second (61% vs. 87%; P < 0.001). CONCLUSIONS: Although patients with treatment-resistant severe asthma cannot always be distinguished from those with difficult-to-treat severe asthma on the basis of baseline clinical characteristics, reduced airflow and elevated fractional exhaled nitric oxide are factors that could distinguish the two groups. Patients diagnosed with severe uncontrolled asthma should be re-evaluated on a regular basis, in order to exclude other diagnoses, to reduce exacerbations, and to identify patients with persistent airflow limitation.

From lip to lab: salty tasting skin is the main clue that raises clinical suspicion of cystic fibrosis in young infants.

AIM: This study developed a clinical decision rule (CDR) to rule in or rule out cystic fibrosis (CF) in the first weeks of life. METHODS: We combined a two-step nonconcurrent birth cohort and a cross-sectional controlled study in which observers and mothers were blinded to confirmatory sweat test results. Neonates from uncomplicated pregnancies and deliveries, with two subsequent tests for immunoreactive trypsinogen (IRT) higher than 70 ng/mL, were eligible to take part. RESULTS: We included 49 CF-affected and 177 CF-unaffected infants with an average age of 34 days. CF-affected infants demonstrated statistically significant differences in weight gain, stool frequency and salty tasting skin from birth. Multivariate analysis showed that the main predictors of CF were salty tasting skin (odds ratio 17.2) and weight gain of <10.5 g per day (odds ratio 4.6). Depending on the CDR score, we obtained the following results: sensitivity (42.9-61.2%), specificity (89.6-96.5%), positive (62.5-77.8%) and negative (85.6-89.1%) predictive value and positive (5.8-12.3) and negative (0.4-0.6) likelihood ratio. CONCLUSION: The CDR could provide a reliable index of clinical suspicion and timely referral for sweat testing in settings without newborn screening programmes and may also be applied to false-negative individuals where such programmes already exist.

Pulmonary radiographic findings in young children with cystic fibrosis.

BACKGROUND: Pulmonary evaluation is one of the greatest challenges in children with cystic fibrosis who are younger than 6 years. Although chest CT can provide the most information for initial and progressive changes in cystic fibrosis, the radiation exposures can lead to significant cumulative exposure in children as they are followed with serial scanning to monitor early and progressive disease. Therefore the systematized study of chest radiographs using the Brasfield score has been used scientifically with the aim of evaluating the evolution of pulmonary abnormalities in children with cystic fibrosis. OBJECTIVE: This study was performed to assess the radiologic findings in children younger than 6 years with cystic fibrosis. We used the Brasfield score to compare radiographs performed in patients with Pseudomonas aeruginosa vs. oxacillin-sensitive Staphylococcus aureus and to compare radiographs in children with early vs. delayed diagnosis. MATERIALS AND METHODS: A total of 254 chest radiographs from 67 children who had undergone material cultures of the airways as part of routine care were evaluated in this cross-sectional study. The statistical analysis was performed by the Kruskal-Wallis test, with a significance level of 5%. RESULTS: Approximately 35.8% of chest radiographs had a Brasfield score lower than 21 points, which is compatible with potentially irreversible pulmonary disease. Brasfield scores decreased (this score decreases with increasing disease severity) in older children, and both bacterial colonization with Pseudomonas and later diagnosis were associated with lower (greater disease) scores. CONCLUSION: The evaluation of radiographs using the Brasfield score demonstrated the most important pulmonary findings in cystic fibrosis and identified the age group when these alterations began to appear more pronounced.

Are measurements of peak nasal flow useful for evaluating nasal obstruction in patients with allergic rhinitis?

BACKGROUND: Nasal obstruction is one of the most bothering allergic rhinitis (AR) symptoms and there is a need for objective parameters to complement clinical evaluation due to blunted perception in many patients. In this study we compare measures of peak nasal inspiratory flow (PNIF) and peak nasal expiratory flow (PNEF) in patients with AR and in individuals without nasal symptoms and correlate them with the perception of nasal obstruction. METHODS: A comparative cross-sectional study was conducted in 64 AR patients and 67 individuals without nasal symptoms aged between 16 and 50 years. All subjects had PNIF and PNEF measures and subjective evaluations of nasal obstruction were done through a visual analogue scale (VAS) and a symptoms questionnaire. RESULTS: The results show a lower PNIF and PNEF in AR patients compared to controls. There was no correlation between VAS score and PNIF and PNEF. There was a weak inverse correlation between PNIF and symptoms score. CONCLUSION: Objective measures of nasal obstruction, especially PNIF, can give useful informations on aspects of the disease dif- ferent from those obtained from the patient`s perception.

Rate and predictors of insufficient sweat volume in very young infants after pilocarpine gel iontophoresis: prospective, population-based study.

OBJECTIVE: To verify the rate and predictors of 'quantity not sufficient' (QNS) among Brazilian infants younger than 3 months with positive newborn screening (NBS) for cystic fibrosis (CF). DESIGN: Prospective, population-based study. SETTING: Public Statewide Newborn Screening Programme where the incidence rate of CF is ≈1:11 000. PATIENTS: Subjects with positive two-tiered immunoreactive trypsinogen. INTERVENTIONS: Sweat induction and collection were performed in the same facility; one sweat sample was obtained per individual. MAIN OUTCOME MEASURES: The QNS rate and its predictors; analysis corresponded to the day of sweat collection. RESULTS: Among the 975 participants, QNS rates for 10 and 15 µL were 3.6% (95% CI 2.5% to 4.9%) and 8.3% (95% CI 6.6% to 10.2%). Infants weighing >3056 and >3845 g and with gestational age higher than 37 weeks had a greater likelihood (5.5 and 6.7, and 2.7 and 5.8 times more, respectively) of avoiding QNS than their peers. CONCLUSION: QNS rates fulfilled the requirements, but predictors differed from those recommended by the Cystic Fibrosis Foundations guidelines.

Comparison of diagnostic methods for pancreatic insufficiency in infants with cystic fibrosis.

OBJECTIVE: The objective of the present study is to compare daily weight gain and laboratory analysis (72-hour fecal fat and steatocrit) with fecal elastase-1 (EL-1) when diagnosing pancreatic insufficiency (PI) in infants with cystic fibrosis (CF). METHODS: A total of 39 infants with CF, diagnosed consecutively by newborn screening at 2 referral centers, were included in the study. Daily weight gain and results of laboratory analysis of stool samples were compared using the κ coefficient and the receiver operator characteristic (ROC) curve. RESULTS: Using the criterion of low daily weight gain, the frequency of PI was 92.3%; using the 72-hour fecal fat, steatocrit, and fecal EL-1 tests, the frequency was 42.3%, 86.2%, and 84.6%, respectively. EL-1 was used as the reference test. It was observed that the criteria of low daily weight gain (<50th percentile) and abnormal steatocrit, used together, showed the highest sensitivity (91.3%) and specificity (83.3%) for the diagnosis of PI. CONCLUSIONS: When fecal EL-1 analysis is not immediately available, low daily weight gain associated with abnormal steatocrit can be adopted as a criterion for initiating pancreatic enzyme replacement therapy in infants with CF; however, EL-1 testing should be performed later for confirmation of PI.

Simulation-based bronchoscopy training: Randomized trial comparing worked example to video introduction.

INTRODUCTION: Learning the complex skill of bronchoscopy involves the integration of cognitive domains and motor skills. The development of simulators has opened up new possibilities in bronchoscopy training. This study aimed at evaluating how effective the modeling example methodology is in training this skill and assessed its effect on cognitive load in learning. METHODS: Forty-seven medical students participating in a simulator-based bronchoscopy training program were randomly allocated to a control group, receiving a video lesson, and the modeling example group. They were evaluated by the simulator's metrics at different time points: pre-, posttest, and 15 days and 12 months after training. Cognitive load was assessed with the modified Paas scale. RESULTS: Simulation-based training was effective for both groups, based on simulator metrics (p < .05). The modeling example group outperformed the control group in all measures at posttest and after 15 days (p < .001). After 12 months, there was a decline in skill in both groups, but the modeling example group performed better (p < .001). Simulation-based training reduced cognitive load, more strongly so in the modeling example group (p < .001). CONCLUSION: The modeling example group showed substantial benefits over the control group, both in reducing the cognitive load in learning and in retaining knowledge and skill after 15 days and 12 months.