An Evaluation of Private Sector Pathways to Diagnosis of Tuberculosis in Chennai, India

Setting Private practitioners are frequently the first point of healthcare contact for patients with tuberculosis (TB) in India. However, inappropriate TB management practices among private practitioners may contribute to delayed TB diagnosis. As new TB diagnostic tests are developed and the national TB control program seeks to better engage the private sector, it is important to understand pathways to TB diagnosis in urban India. Design A cross-sectional study was conducted among patients and practitioners in Chennai city from January 2014 to February 2015. Patient participants were diagnosed with TB in the private sector and referred for TB treatment through a public-private mix program in Chennai. Practitioners practicing in the private sector, who saw at least one TB patient per year, were randomly selected from both the general community and a list of practitioners who referred patients to the public-private mix program. Cross-section interviews were conducted with 289 patients and 228 practitioners using standardized questionnaires. Results Among 212 patients with pulmonary TB, 90% first contacted a formal private provider, and 78% were diagnosed by the first or second provider seen after a median of three visits per provider. Median total delay was 52 days (Mean 69). Consulting an informal (rather than formally trained) provider first, was associated with an increase in risk of prolonged total delay >90 days (aRR 2.5, 95%CI: 1.3-4.5). Among 228 private practitioners, only 52% of practitioners sent >5% of patients with cough for TB testing, 83% used smear microscopy for diagnosis, and 22% notified TB cases to authorities. For new patients with pulmonary TB, 30% of practitioners reported referring all patients for treatment, while 70% (160/228) listed 27 different regimens; 78% (125/160) of these prescribed a regimen classified as consistent with ISTC. Under half (48%, 110/228) of all practitioners utilized any point-of-care (POC) tests in their clinics. Providers using POC tests were more likely to work in hospitals (56% vs. 43%, P=0.05) and less likely to be chest specialists (21% vs. 54%, P<0.001). When asked about using a hypothetical, novel POC test for TB that was accurate, took 20 minutes, and required no equipment, only half (51%, 117/228) of all providers would use the test in-house. Conclusion Even among patients seeking care in the formal private sector in Chennai, diagnostic delays are substantial. TB management practices in India’s urban private sector are heterogeneous and often suboptimal. Novel strategies are required to engage private providers and integrate new diagnostics into the private system to improve diagnostic capacity and decrease TB transmission in India

Latent Class Analysis of Prenatal Substance Exposure and Child Behavioral Outcomes.

OBJECTIVES: To predict behavioral disruptions in middle childhood, we identified latent classes of prenatal substance use. STUDY DESIGN: As part of the Environmental influences on Child Health Outcomes Program, we harmonized prenatal substance use data and child behavior outcomes from 2195 women and their 6- to 11-year-old children across 10 cohorts in the US and used latent class-adjusted regression models to predict parent-rated child behavior. RESULTS: Three latent classes fit the data: low use (90.5%; n&nbsp;=&nbsp;1986), primarily using no substances; licit use (6.6%; n&nbsp;=&nbsp;145), mainly using nicotine with a moderate likelihood of using alcohol and marijuana; and illicit use (2.9%; n&nbsp;=&nbsp;64), predominantly using illicit substances along with a moderate likelihood of using licit substances. Children exposed to primarily licit substances in utero had greater levels of externalizing behavior than children exposed to low or no substances (P&nbsp;=&nbsp;.001, d&nbsp;=&nbsp;.64). Children exposed to illicit substances in utero showed small but significant elevations in internalizing behavior than children exposed to low or no substances (P&nbsp;&lt;&nbsp;.001, d&nbsp;=&nbsp;.16). CONCLUSIONS: The differences in prenatal polysubstance use may increase risk for specific childhood problem behaviors; however, child outcomes appeared comparably adverse for both licit and illicit polysubstance exposure. We highlight the need for similar multicohort, large-scale studies to examine childhood outcomes based on prenatal substance use profiles

Latent Class Analysis of Prenatal Substance Exposure and Child Behavioral Outcomes

Objectives To predict behavioral disruptions in middle childhood, we identified latent classes of prenatal substance use. Study design As part of the Environmental influences on Child Health Outcomes Program, we harmonized prenatal substance use data and child behavior outcomes from 2195 women and their 6- to 11-year-old children across 10 cohorts in the US and used latent class–adjusted regression models to predict parent-rated child behavior. Results Three latent classes fit the data: low use (90.5%; n = 1986), primarily using no substances; licit use (6.6%; n = 145), mainly using nicotine with a moderate likelihood of using alcohol and marijuana; and illicit use (2.9%; n = 64), predominantly using illicit substances along with a moderate likelihood of using licit substances. Children exposed to primarily licit substances in utero had greater levels of externalizing behavior than children exposed to low or no substances (P = .001, d = .64). Children exposed to illicit substances in utero showed small but significant elevations in internalizing behavior than children exposed to low or no substances (P &lt; .001, d = .16). Conclusions The differences in prenatal polysubstance use may increase risk for specific childhood problem behaviors; however, child outcomes appeared comparably adverse for both licit and illicit polysubstance exposure. We highlight the need for similar multicohort, large-scale studies to examine childhood outcomes based on prenatal substance use profiles

An Evaluation of Private Sector Pathways to Diagnosis of Tuberculosis in Chennai, India

Setting Private practitioners are frequently the first point of healthcare contact for patients with tuberculosis (TB) in India. However, inappropriate TB management practices among private practitioners may contribute to delayed TB diagnosis. As new TB diagnostic tests are developed and the national TB control program seeks to better engage the private sector, it is important to understand pathways to TB diagnosis in urban India. Design A cross-sectional study was conducted among patients and practitioners in Chennai city from January 2014 to February 2015. Patient participants were diagnosed with TB in the private sector and referred for TB treatment through a public-private mix program in Chennai. Practitioners practicing in the private sector, who saw at least one TB patient per year, were randomly selected from both the general community and a list of practitioners who referred patients to the public-private mix program. Cross-section interviews were conducted with 289 patients and 228 practitioners using standardized questionnaires. Results Among 212 patients with pulmonary TB, 90% first contacted a formal private provider, and 78% were diagnosed by the first or second provider seen after a median of three visits per provider. Median total delay was 52 days (Mean 69). Consulting an informal (rather than formally trained) provider first, was associated with an increase in risk of prolonged total delay >90 days (aRR 2.5, 95%CI: 1.3-4.5). Among 228 private practitioners, only 52% of practitioners sent >5% of patients with cough for TB testing, 83% used smear microscopy for diagnosis, and 22% notified TB cases to authorities. For new patients with pulmonary TB, 30% of practitioners reported referring all patients for treatment, while 70% (160/228) listed 27 different regimens; 78% (125/160) of these prescribed a regimen classified as consistent with ISTC. Under half (48%, 110/228) of all practitioners utilized any point-of-care (POC) tests in their clinics. Providers using POC tests were more likely to work in hospitals (56% vs. 43%, P=0.05) and less likely to be chest specialists (21% vs. 54%, P<0.001). When asked about using a hypothetical, novel POC test for TB that was accurate, took 20 minutes, and required no equipment, only half (51%, 117/228) of all providers would use the test in-house. Conclusion Even among patients seeking care in the formal private sector in Chennai, diagnostic delays are substantial. TB management practices in India’s urban private sector are heterogeneous and often suboptimal. Novel strategies are required to engage private providers and integrate new diagnostics into the private system to improve diagnostic capacity and decrease TB transmission in India

Risk factors for SARS-CoV-2 infection and transmission in households with children with asthma and allergy: A prospective surveillance study

BACKGROUND: Whether children and people with asthma and allergic diseases are at increased risk for severe acute respiratory syndrome virus 2 (SARS-CoV-2) infection is unknown. OBJECTIVE: Our aims were to determine the incidence of SARS-CoV-2 infection in households with children and to also determine whether self-reported asthma and/or other allergic diseases are associated with infection and household transmission. METHODS: For 6 months, biweekly nasal swabs and weekly surveys were conducted within 1394 households (N = 4142 participants) to identify incident SARS-CoV-2 infections from May 2020 to February 2021, which was the pandemic period largely before a vaccine and before the emergence of SARS-CoV-2 variants. Participant and household infection and household transmission probabilities were calculated by using time-to-event analyses, and factors associated with infection and transmission risk were determined by using regression analyses. RESULTS: In all, 147 households (261 participants) tested positive for SARS-CoV-2. The household SARS-CoV-2 infection probability was 25.8%; the participant infection probability was similar for children (14.0% [95% CI = 8.0%-19.6%]), teenagers (12.1% [95% CI = 8.2%-15.9%]), and adults (14.0% [95% CI = 9.5%-18.4%]). Infections were symptomatic in 24.5% of children, 41.2% of teenagers, and 62.5% of adults. Self-reported doctor-diagnosed asthma was not a risk factor for infection (adjusted hazard ratio [aHR] = 1.04 [95% CI = 0.73-1.46]), nor was upper respiratory allergy or eczema. Self-reported doctor-diagnosed food allergy was associated with lower infection risk (aHR = 0.50 [95% CI = 0.32-0.81]); higher body mass index was associated with increased infection risk (aHR per 10-point increase = 1.09 [95% CI = 1.03-1.15]). The household secondary attack rate was 57.7%. Asthma was not associated with household transmission, but transmission was lower in households with food allergy (adjusted odds ratio = 0.43 [95% CI = 0.19-0.96]; P = .04). CONCLUSION: Asthma does not increase the risk of SARS-CoV-2 infection. Food allergy is associated with lower infection risk, whereas body mass index is associated with increased infection risk. Understanding how these factors modify infection risk may offer new avenues for preventing infection

Expression quantitative trait locus fine mapping of the 17q12–21 asthma locus in African American children: a genetic association and gene expression study

Background: African ancestry is associated with a higher prevalence and greater severity of asthma than European ancestries, yet genetic studies of the most common locus associated with childhood-onset asthma, 17q12–21, in African Americans have been inconclusive. The aim of this study was to leverage both the phenotyping of the Children's Respiratory and Environmental Workgroup (CREW) birth cohort consortium, and the reduced linkage disequilibrium in African Americans, to fine map the 17q12–21 locus. Methods: We first did a genetic association study and meta-analysis using 17q12–21 tag single-nucleotide polymorphisms (SNPs) for childhood-onset asthma in 1613 European American and 870 African American children from the CREW consortium. Nine tag SNPs were selected based on linkage disequilibrium patterns at 17q12–21 and their association with asthma, considering the effect allele under an additive model (0, 1, or 2 effect alleles). Results were meta-analysed with publicly available summary data from the EVE consortium (on 4303 European American and 3034 African American individuals) for seven of the nine SNPs of interest. Subsequently, we tested for expression quantitative trait loci (eQTLs) among the SNPs associated with childhood-onset asthma and the expression of 17q12–21 genes in resting peripheral blood mononuclear cells (PBMCs) from 85 African American CREW children and in upper airway epithelial cells from 246 African American CREW children; and in lower airway epithelial cells from 44 European American and 72 African American adults from a case-control study of asthma genetic risk in Chicago (IL, USA). Findings: 17q12–21 SNPs were broadly associated with asthma in European Americans. Only two SNPs (rs2305480 in gasdermin-B [GSDMB] and rs8076131 in ORMDL sphingolipid biosynthesis regulator 3 [ORMDL3]) were associated with asthma in African Americans, at a Bonferroni-corrected threshold of p<0·0055 (for rs2305480_G, odds ratio [OR] 1·36 [95% CI 1·12–1·65], p=0·0014; and for rs8076131_A, OR 1·37 [1·13–1·67], p=0·0010). In upper airway epithelial cells from African American children, genotype at rs2305480 was the most significant eQTL for GSDMB (eQTL effect size [β] 1·35 [95% CI 1·25–1·46], p<0·0001), and to a lesser extent showed an eQTL effect for post-GPI attachment to proteins phospholipase 3 (β 1·15 [1·08–1·22], p<0·0001). No SNPs were eQTLs for ORMDL3. By contrast, in PBMCs, the five core SNPs were associated only with expression of GSDMB and ORMDL3. Genotype at rs12936231 (in zona pellucida binding protein 2) showed the strongest associations across both genes (for GSDMB, eQTLβ 1·24 [1·15–1·32], p<0·0001; and for ORMDL3 (β 1·19 [1·12–1·24], p<0·0001). The eQTL effects of rs2305480 on GSDMB expression were replicated in lower airway cells from African American adults (β 1·29 [1·15–1·44], p<0·0001). Interpretation: Our study suggests that SNPs regulating GSDMB expression in airway epithelial cells have a major role in childhood-onset asthma, whereas SNPs regulating the expression levels of 17q12–21 genes in resting blood cells are not central to asthma risk. Our genetic and gene expression data in African Americans and European Americans indicated GSDMB to be the leading candidate gene at this important asthma locus.6 month embargo; published: 01 May 2020This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]