Step-Up Therapy in Black Children and Adults with Poorly Controlled Asthma.

BACKGROUND: Morbidity from asthma is disproportionately higher among black patients than among white patients, and black patients constitute the minority of participants in trials informing treatment. Data indicate that patients with inadequately controlled asthma benefit more from addition of a long-acting beta-agonist (LABA) than from increased glucocorticoids; however, these data may not be informative for treatment in black patients. METHODS: We conducted two prospective, randomized, double-blind trials: one involving children and the other involving adolescents and adults. In both trials, the patients had at least one grandparent who identified as black and had asthma that was inadequately controlled with low-dose inhaled glucocorticoids. We compared combinations of therapy, which included the addition of a LABA (salmeterol) to an inhaled glucocorticoid (fluticasone propionate), a step-up to double to quintuple the dose of fluticasone, or both. The treatments were compared with the use of a composite measure that evaluated asthma exacerbations, asthma-control days, and lung function; data were stratified according to genotypic African ancestry. RESULTS: When quintupling the dose of fluticasone (to 250 µg twice a day) was compared with adding salmeterol (50 µg twice a day) and doubling the fluticasone (to 100 µg twice a day), a superior response occurred in 46% of the children with quintupling the fluticasone and in 46% of the children with doubling the fluticasone and adding salmeterol (P = 0.99). In contrast, more adolescents and adults had a superior response to added salmeterol than to an increase in fluticasone (salmeterol-low-dose fluticasone vs. medium-dose fluticasone, 49% vs. 28% [P = 0.003]; salmeterol-medium-dose fluticasone vs. high-dose fluticasone, 49% vs. 31% [P = 0.02]). Neither the degree of African ancestry nor baseline biomarkers predicted a superior response to specific treatments. The increased dose of inhaled glucocorticoids was associated with a decrease in the ratio of urinary cortisol to creatinine in children younger than 8 years of age. CONCLUSIONS: In contrast to black adolescents and adults, almost half the black children with poorly controlled asthma had a superior response to an increase in the dose of an inhaled glucocorticoid and almost half had a superior response to the addition of a LABA. (Funded by the National Heart, Lung, and Blood Institute; BARD ClinicalTrials.gov number, NCT01967173.).

Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations.

BACKGROUND: Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited. METHODS: We studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 µg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (high-dose group; fluticasone at a dose of 220 µg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids. RESULTS: The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the high-dose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P=0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellow-zone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P=0.06). CONCLUSIONS: In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129 .).

Levofloxacin based non-rifampicin anti-tuberculous therapy: An effective alternative in renal transplant recipients in resource limited setting.

INTRODUCTION: Rifampicin is one of the most effective components of anti-tuberculous therapy (ATT). Since rifampicin is a hepatic enzyme (CYP3A4) inducer, in a post-renal transplant recipient, the dose of calcineurin inhibitors needs to be up-regulated and frequently monitored. In resource-limited (low- and lower-middle-income countries) setting this is not always feasible. Therefore, we evaluated a non-rifampicin-based ATT using levofloxacin in kidney transplant recipients. METHODS: We retrospectively studied the medical records of renal transplant recipients diagnosed with tuberculosis in our institute between 2014 and 2017. After a brief discussion with patients regarding the nature and course of ATT, those who opted for a non-rifampicin based therapy due to financial constraints were included in the study and followed for a minimum of 6 months period after the completion of ATT. RESULTS: Out of the 550 renal transplant recipients, 67 (12.2%) developed tuberculosis after a median period of 24 (1-228) months following transplantation, of them, 64 patients opted for non-rifampicin-based ATT. The mean age was 37.6 years. Only 25% were given anti-thymocyte globulin based induction, while the majority (56; 87.5%) of them were on tacrolimus-based triple-drug maintenance therapy. Extrapulmonary tuberculosis was noted in 33% of cases, while 12 (18.7%) had disseminated disease. The median duration of treatment was 12 months and the cure rate of 93.7% (n = 60) was achieved at the end of therapy. CONCLUSION: Levofloxacin based ATT appears to be a safe and effective alternative of rifampicin in kidney transplant recipients who cannot afford heightened tacrolimus dosage.

Acetaminophen versus Ibuprofen in Young Children with Mild Persistent Asthma.

BACKGROUND: Studies have suggested an association between frequent acetaminophen use and asthma-related complications among children, leading some physicians to recommend that acetaminophen be avoided in children with asthma; however, appropriately designed trials evaluating this association in children are lacking. METHODS: In a multicenter, prospective, randomized, double-blind, parallel-group trial, we enrolled 300 children (age range, 12 to 59 months) with mild persistent asthma and assigned them to receive either acetaminophen or ibuprofen when needed for the alleviation of fever or pain over the course of 48 weeks. The primary outcome was the number of asthma exacerbations that led to treatment with systemic glucocorticoids. Children in both groups received standardized asthma-controller therapies that were used in a simultaneous, factorially linked trial. RESULTS: Participants received a median of 5.5 doses (interquartile range, 1.0 to 15.0) of trial medication; there was no significant between-group difference in the median number of doses received (P=0.47). The number of asthma exacerbations did not differ significantly between the two groups, with a mean of 0.81 per participant with acetaminophen and 0.87 per participant with ibuprofen over 46 weeks of follow-up (relative rate of asthma exacerbations in the acetaminophen group vs. the ibuprofen group, 0.94; 95% confidence interval, 0.69 to 1.28; P=0.67). In the acetaminophen group, 49% of participants had at least one asthma exacerbation and 21% had at least two, as compared with 47% and 24%, respectively, in the ibuprofen group. Similarly, no significant differences were detected between acetaminophen and ibuprofen with respect to the percentage of asthma-control days (85.8% and 86.8%, respectively; P=0.50), use of an albuterol rescue inhaler (2.8 and 3.0 inhalations per week, respectively; P=0.69), unscheduled health care utilization for asthma (0.75 and 0.76 episodes per participant, respectively; P=0.94), or adverse events. CONCLUSIONS: Among young children with mild persistent asthma, as-needed use of acetaminophen was not shown to be associated with a higher incidence of asthma exacerbations or worse asthma control than was as-needed use of ibuprofen. (Funded by the National Institutes of Health; AVICA ClinicalTrials.gov number, NCT01606319.).

A Cross-sectional Study on Learning Preferences for Research Methodology among Medical Students.

BACKGROUND: The modalities of learning could be Visual, Auditory, Reading/ writing, and Kinesthetic (VARK). VARK concept has been used to know the learning preferences among First Year Medical Students. But learning preferences for "Research Methodology" have rarely been reported. OBJECTIVE: This study was conducted to know the learning preferences for "Research Methodology" using VARK concept. METHODS: A questionnaire-based study was conducted among medical undergraduate students who had completed their student research project during their 4th semester. The questionnaire was constructed using VARK concept to know: 1. Learning preference of research methodology, 2. Characteristics of learning preference of participants are classified under "Visual(V), Auditory(A), Read/write(R), and Kinaesthetic(K). The students were approached in the classrooms, and the data was collected and was analysed using SPSS version 11.5. Results were expressed as proportions in appropriate tables and graphs. RESULTS: Totally 157 students were participated in the study. Most (1164/1570 [74.1%]) of them expressed Unimodal learning preference as compared to Multimodal learning (84/1570 [5.4%]). Majority preferred Auditory (641/1560 [40.8%]) followed by Visual (542/1570 [34.5%]) for learning "Research Methodology". This study showed that gender of the students did not influence learning preference. However, the total number of preference for "Kinaesthetic" in those who had additional research experience through ICMR-STS and workshop on research methodology are more compared to those who didn't. CONCLUSION: Unimodal with Auditory followed by Visual mode was preferred for learning "Research Methodology".

A computable phenotype for asthma case identification in adult and pediatric patients: External validation in the Chicago Area Patient-Outcomes Research Network (CAPriCORN).

Objective: Comprehensive, rapid, and accurate identification of patients with asthma for clinical care and engagement in research efforts is needed. The original development and validation of a computable phenotype for asthma case identification occurred at a single institution in Chicago and demonstrated excellent test characteristics. However, its application in a diverse payer mix, across different health systems and multiple electronic health record vendors, and in both children and adults was not examined. The objective of this study is to externally validate the computable phenotype across diverse Chicago institutions to accurately identify pediatric and adult patients with asthma. Methods: A cohort of 900 asthma and control patients was identified from the electronic health record between January 1, 2012 and November 30, 2014. Two physicians at each site independently reviewed the patient chart to annotate cases. Results: The inter-observer reliability between the physician reviewers had a κ-coefficient of 0.95 (95% CI 0.93-0.97). The accuracy, sensitivity, specificity, negative predictive value, and positive predictive value of the computable phenotype were all above 94% in the full cohort. Conclusions: The excellent positive and negative predictive values in this multi-center external validation study establish a useful tool to identify asthma cases in in the electronic health record for research and care. This computable phenotype could be used in large-scale comparative-effectiveness trials.

Parental coping, depressive symptoms, and children's asthma control and school attendance in low-income, racially, and ethnically diverse urban families.

OBJECTIVE: Low-income urban children of color are at elevated risk for poor asthma control. This cross-sectional study examined associations among parents' coping (primary control, secondary control, and disengagement), parental depressive symptoms, and children's asthma outcomes (asthma control and school attendance) in a predominantly low-income, racially/ethnically diverse sample of families. METHODS: Parents (N = 78; 90% female) of children (33% female; 46% Black; 38% Latino) aged 5-17 years (M = 9.5 years) reported on their own coping and depressive symptoms, their child's asthma control, and full and partial days of school missed due to asthma. RESULTS: Parents' secondary control coping (i.e., coping efforts to accommodate/adapt to asthma-related stressors) was negatively correlated, and disengagement coping (i.e. coping efforts to avoid/detach from stressors) was positively correlated, with their depressive symptoms. Secondary control coping was also correlated with fewer partial days of school missed. Primary control coping (i.e., coping efforts to change stressors) was not associated with depressive symptoms or asthma outcomes. Parents' depressive symptoms were also positively correlated with poorer asthma control and partial days of school missed. Regression models showed direct and indirect effects of secondary control and disengagement coping on asthma outcomes via depressive symptoms, after controlling for demographic factors. CONCLUSIONS: Parents' secondary control and disengagement coping are related to children's asthma outcomes. Secondary control coping may support parents' mental health and children's asthma control in low-income urban families.

Individualized therapy for persistent asthma in young children.

BACKGROUND: Phenotypic presentations in young children with asthma are varied and might contribute to differential responses to asthma controller medications. METHODS: The Individualized Therapy for Asthma in Toddlers study was a multicenter, randomized, double-blind, double-dummy clinical trial in children aged 12 to 59 months (n = 300) with asthma necessitating treatment with daily controller (Step 2) therapy. Participants completed a 2- to 8-week run-in period followed by 3 crossover periods with daily inhaled corticosteroids (ICSs), daily leukotriene receptor antagonists, and as-needed ICS treatment coadministered with albuterol. The primary outcome was differential response to asthma medication based on a composite measure of asthma control. The primary analysis involved 2 stages: determination of differential response and assessment of whether 3 prespecified features (aeroallergen sensitization, previous exacerbations, and sex) predicted a differential response. RESULTS: Seventy-four percent (170/230) of children with analyzable data had a differential response to the 3 treatment strategies. Within differential responders, the probability of best response was highest for a daily ICS and was predicted by aeroallergen sensitization but not exacerbation history or sex. The probability of best response to daily ICS was further increased in children with both aeroallergen sensitization and blood eosinophil counts of 300/µL or greater. In these children daily ICS use was associated with more asthma control days and fewer exacerbations compared with the other treatments. CONCLUSIONS: In young children with asthma necessitating Step 2 treatment, phenotyping with aeroallergen sensitization and blood eosinophil counts is useful for guiding treatment selection and identifies children with a high exacerbation probability for whom treatment with a daily ICS is beneficial despite possible risks of growth suppression.

PLA2R antibodies, glomerular PLA2R deposits and variations in PLA2R1 and HLA-DQA1 genes in primary membranous nephropathy in South Asians.

BACKGROUND: Antibodies to M-type phospholipase A2 receptor (PLA2R) correlate with clinical activity of primary membranous nephropathy (PMN). Risk alleles in PLA2R1 and HLA-DQA1 genes are associated with PMN. Whether these alleles are associated with the development of anti-PLA2R is unknown. In this prospective study we evaluated anti-PLA2R, enhanced glomerular staining for PLA2R and variations in PLA2R1 and HLA-DQA1 genes in Indian patients with PMN and examined their association with response to treatment. METHODS: A total of 114 adult PMN patients were studied. Anti-PLA2R was estimated before treatment and after 6 and 12 months of therapy. Enhanced glomerular staining for PLA2R was assessed on fresh frozen tissue. Genotype analysis was done on recruited patients and 95 healthy controls by TaqMan assays for six single-nucleotide polymorphisms (SNPs; rs4664308, rs3749119, rs3749117, rs4664308, rs3828323 and rs2187668). Patients were followed up monthly for a period of 12 months. RESULTS: Of 114 patients, 66.7% showed elevated serum anti-PLA2R by ELISA and 64.9% by indirect immunofluorescence. About 75% had enhanced glomerular staining for PLA2R. A total of 82% of patients had PLA2R-related disease. Reduction in serum anti-PLA2R titer had a significant association with remission of nephrotic syndrome (P = 0.0003) at 6 and 12 months. More than 85% of patients showing >90% reduction in the anti-PLA2R titer achieved remission of the nephrotic state, whereas of those showing <50% reduction in titers, 87.5% had persistent nephrotic state. The SNPs rs3749119, rs3749117, rs4664308 in PLA2R1 and rs2187668 in HLA-DQA1 were significantly associated with PMN. The SNP rs2187668 was associated with anti-PLA2R positivity. Patients with a high-risk genotype had higher anti-PLA2R levels. CONCLUSION: To conclude, anti-PLA2R and enhanced glomerular PLA2R staining are found in more than two-thirds of Indian PMN cases. A reduction in the anti-PLA2R titer correlated with response to therapy.

Physician perceptions of children's coping with asthma are associated with children's psychosocial and disease functioning.

INTRODUCTION: Low-income, ethnic minority children disproportionately face poor asthma control, and poorly controlled asthma is related to psychosocial difficulties. This study assessed physician reports of coping in child patients and examined associations between physician reports of child coping and parent and child reports of children's coping, psychosocial, and asthma outcomes (asthma-related stress, emotional and behavioral problems, asthma control, and school missed due to asthma). METHOD: Physicians reported on coping in their patients (N = 67) ages 5-17 with asthma. Parents reported on child coping, asthma-related stress, emotional and behavioral problems, asthma control, and school missed due to asthma. Children ages 9-17 provided self-reports. RESULTS: Physicians' reports of primary control coping (e.g., problem solving) and secondary control coping (e.g., cognitive restructuring) were not associated with parent ratings of corresponding coping strategies, but physician reports of disengagement coping (e.g., avoidance) were correlated with parent reports of disengagement and secondary control coping. Physician perceptions of higher child primary control, and lower disengagement, were correlated with less parent-reported stress, better asthma control, and for primary control, fewer partial days of school missed. Physician reports were not correlated with child reports of coping, but physician reports of disengagement were correlated with child-reported conduct problems. DISCUSSION: Findings suggest that physician reports of child coping provide independent information from parent and child reports of coping, and could be leveraged to identify and intervene with patients who are at elevated risk for poor outcomes. (PsycINFO Database Record

Coping with Asthma in Racially and Ethnically Diverse Urban Children: The Role of Emotional Problems in Disease Control.

This study examined cross-sectional associations among coping, mental health, and asthma outcomes in racially/ethnically diverse urban children. Children (N=42; 65% female) ages 9 to 17 (M=11.9) years old and their parents reported on the child's coping, emotional and conduct problems, asthma control, and school missed due to asthma. Higher child and parent reported secondary control coping was correlated with fewer mental health problems and better child reported asthma control. Child reported emotional problems partially accounted for associations between child and parent reported secondary control coping and child reported asthma control. Secondary control coping may improve asthma by reducing emotional difficulties.

Risk factors for cranial nerve deficits during carotid endarterectomy: a retrospective study.

BACKGROUND: Cranial nerve deficits during CEA are a known complication. The purpose of this study is to evaluate if significant changes in somatosensory evoked potentials and electroencephalography increase cranial nerve deficits during CEA. PROCEDURES: This is an observational retrospective case-control study analyzed with data collected from patients who underwent CEA at the University of Pittsburgh Medical Center. Five hundred and eighty-seven patients were included in the final analysis. Due to the small number of cranial nerve deficits and the comparatively large number of potential covariates, we used a regression analysis with Bayesian shrinkage. FINDINGS: Analysis was performed on 587 patients, of which a total of 11 (1.8%) cases of cranial nerve deficits were recorded. The marginal mandibular branch of the facial nerve was injured in nine (81%) patients and hypoglossal nerve was injured in two (19%) patients. Of the 11 patients, 9 cases resolved by the time of discharge, the 2 cases that persisted both were injuries to the facial nerve. Multivariate analysis using Bayesian shrinkage showed that after adjusting for all risk factors only IOM changes increased the risk of cranial nerve deficits (OR 38.47, 95% CI 7.73, 191.42). CONCLUSIONS: Cranial nerve injury is 38 times more likely in patients who experienced a change in IOM during CEA shunt. Future studies examining the effect of stretch and the degree of retraction on the CN might be more helpful in reducing cranial nerve deficits.

Mallampati score and pediatric obstructive sleep apnea.

RATIONALE: Pediatric obstructive sleep apnea (OSA) is common, and a delay in diagnosis can lead to significant morbidity. Polysomnography (PSG) is the gold standard for the diagnosis of OSA. However, difficulty accessing PSG due to the relative shortage of sleep centers with pediatric expertise can lead to a delay in the diagnosis and management of OSA. OBJECTIVES: To assess the utility of Mallampati score (sitting and supine) in predicting the presence and severity of OSA in children. METHODS: A retrospective study of 158 children from a single pediatric sleep center. All patients had a PSG and a physical examination documenting Mallampati score. The Mallampati score, tonsillar size, age, sex, and apnea hypopnea index (AHI) were analyzed. Odds ratio of having pediatric OSA (AHI > 1) with increase in Mallampati score and tonsillar size were calculated. MEASUREMENTS AND MAIN RESULTS: A significant correlation was found between Mallampati score, tonsillar size, and AHI. For every point increase in the Mallampati score, the odds ratio of having OSA increased by more than 6-fold. For every point increase in tonsillar size, the odds ratio of having OSA increased by more than 2-fold. CONCLUSIONS: Mallampati score and tonsillar size are independent predictors of OSA. Oral examination including Mallampati score and tonsillar size should be considered when evaluating a patient for OSA. They can be used to prioritize children who may need PSG.