IMPORTANCE: Sleep is vital to children’s biopsychosocial development. Inadequate sleep quantity and quality is a public health concern with an array of detrimental health outcomes. Portable mobile ...and media devices have become a ubiquitous part of children’s lives and may affect their sleep duration and quality. OBJECTIVE: To conduct a systematic review and meta-analysis to examine whether there is an association between portable screen-based media device (eg, cell phones and tablet devices) access or use in the sleep environment and sleep outcomes. DATA SOURCES: A search strategy consisting of gray literature and 24 Medical Subject Headings was developed in Ovid MEDLINE and adapted for other databases between January 1, 2011, and June 15, 2015. Searches of the published literature were conducted across 12 databases. No language restriction was applied. STUDY SELECTION: The analysis included randomized clinical trials, cohort studies, and cross-sectional study designs. Inclusion criteria were studies of school-age children between 6 and 19 years. Exclusion criteria were studies of stationary exposures, such as televisions or desktop or personal computers, or studies investigating electromagnetic radiation. DATA EXTRACTION AND SYNTHESIS: Of 467 studies identified, 20 cross-sectional studies were assessed for methodological quality. Two reviewers independently extracted data. MAIN OUTCOMES AND MEASURES: The primary outcomes were inadequate sleep quantity, poor sleep quality, and excessive daytime sleepiness, studied according to an a priori protocol. RESULTS: Twenty studies were included, and their quality was assessed. The studies involved 125 198 children (mean SD age, 14.5 2.2 years; 50.1% male). There was a strong and consistent association between bedtime media device use and inadequate sleep quantity (odds ratio OR, 2.17; 95% CI, 1.42-3.32) (P < .001, I2 = 90%), poor sleep quality (OR, 1.46; 95% CI, 1.14-1.88) (P = .003, I2 = 76%), and excessive daytime sleepiness (OR, 2.72; 95% CI, 1.32-5.61) (P = .007, I2 = 50%). In addition, children who had access to (but did not use) media devices at night were more likely to have inadequate sleep quantity (OR, 1.79; 95% CI, 1.39-2.31) (P < .001, I2 = 64%), poor sleep quality (OR, 1.53; 95% CI, 1.11-2.10) (P = .009, I2 = 74%), and excessive daytime sleepiness (OR, 2.27; 95% CI, 1.54-3.35) (P < .001, I2 = 24%). CONCLUSIONS AND RELEVANCE: To date, this study is the first systematic review and meta-analysis of the association of access to and the use of media devices with sleep outcomes. Bedtime access to and use of a media device were significantly associated with the following: inadequate sleep quantity, poor sleep quality, and excessive daytime sleepiness. An integrated approach among teachers, health care professionals, and parents is required to minimize device access at bedtime, and future research is needed to evaluate the influence of the devices on sleep hygiene and outcomes.
Transmission is contributing to the slow decline of tuberculosis (TB) incidence globally. Drivers of TB transmission in India, the country estimated to carry a quarter of the World's burden, are not ...well studied. We conducted a genomic epidemiology study to compare epidemiological success, host factors and drug resistance (DR) among the four major Mycobacterium tuberculosis (Mtb) lineages (L1-4) circulating in Pune, India.
We performed whole-genome sequencing (WGS) of Mtb sputum culture-positive isolates from participants in two prospective cohort studies and predicted genotypic susceptibility using a validated random forest model. We used maximum likelihood estimation to build phylogenies. We compared lineage specific phylogenetic and time-scaled metrics to assess epidemiological success.
Of the 642 isolates that underwent WGS, 612 met sequence quality criteria. Most isolates belonged to L3 (44.6%). The majority (61.1%) of multidrug-resistant isolates belonged to L2 (P < 0.001). In molecular dating, L2 demonstrated a higher rate and more recent resistance acquisition. We measured higher clustering, and time-scaled haplotypic density (THD) for L4 and L2 compared to L3 and/or L1 suggesting higher epidemiological success. L4 demonstrated higher THD and clustering (OR 5.1 (95% CI 2.3-12.3) in multivariate models controlling for host factors and DR.
L2 shows a higher frequency of DR and both L2 and L4 demonstrate evidence of higher epidemiological success than L3 or L1 in the study setting. Our findings highlight the need for contact tracing around TB cases, and heightened surveillance of TB DR in India.
Abstract
Background
The relationships between first-line drug concentrations and clinically important outcomes among patients with tuberculosis (TB) remain poorly understood.
Methods
We enrolled a ...prospective cohort of patients with new pulmonary TB receiving thrice-weekly treatment in India. The maximum plasma concentration of each drug was determined at months 1 and 5 using blood samples drawn 2 hours postdose. Subtherapeutic cutoffs were: rifampicin <8 µg/mL, isoniazid <3 µg/mL, and pyrazinamide <20 µg/mL. Factors associated with lower log-transformed drug concentrations, unfavorable outcomes (composite of treatment failure, all-cause mortality, and recurrence), and individual outcomes were examined using Poisson regression models.
Results
Among 404 participants, rifampicin, isoniazid, and pyrazinamide concentrations were subtherapeutic in 85%, 29%, and 13%, respectively, at month 1 (with similar results for rifampicin and isoniazid at month 5). Rifampicin concentrations were lower with human immunodeficiency virus coinfection (median, 1.6 vs 4.6 µg/mL; P = .015). Unfavorable outcome was observed in 19%; a 1-μg/mL decrease in rifampicin concentration was independently associated with unfavorable outcome (adjusted incidence rate ratio aIRR, 1.21 95% confidence interval {CI}, 1.01–1.47) and treatment failure (aIRR, 1.16 95% CI, 1.05–1.28). A 1-μg/mL decrease in pyrazinamide concentration was associated with recurrence (aIRR, 1.05 95% CI, 1.01–1.11).
Conclusions
Rifampicin concentrations were subtherapeutic in most Indian patients taking a thrice-weekly TB regimen, and low rifampicin and pyrazinamide concentrations were associated with poor outcomes. Higher or more frequent dosing is needed to improve TB treatment outcomes in India.
In a prospective cohort of patients with newly diagnosed pulmonary tuberculosis receiving standard thrice-weekly antituberculosis treatment in India, lower rifampicin concentration was associated with Human Immunodeficiency Virus coinfection and independently associated with unfavorable treatment outcomes.
Evidence describing the impact of diabetes mellitus (DM) on the recurrence and mutation rate of Mycobacterium tuberculosis (Mtb) is limited.
This study was nested in 3 cohort studies of tuberculosis ...(TB) patients with and without DM in India. Paired Mtb isolates recovered at baseline and treatment failure/recurrence underwent whole genome sequencing. We compared acquisition of single-nucleotide polymorphisms (SNPs), TB drug resistance mutations, and type of recurrence (endogenous reactivation <8 SNPs or exogenous reinfection ≥8 SNPs) by DM status.
Of 1633 enrolled in the 3 parent cohorts, 236 (14.5%) had microbiologically confirmed TB treatment failure/recurrence; 76 Mtb isolate pairs were available for sequencing (22 in TB-DM and 54 in TB-only). The SNP acquisition rate was overall was 0.43 (95% confidence interval CI, .25-.64) per 1 person-year (PY); 0.77 (95% CI, .40-1.35) per 1 PY, and 0.44 (95% CI, .19-.86) per 1 PY at treatment failure and recurrence, respectively. Significant difference in SNP rates by DM status was seen at recurrence (0.21 95% CI, .04-.61) per 1 PY for TB-only vs 1.28 (95% CI, .41-2.98) per 1 PY for TB-DM; P = .02). No significant difference in SNP rates by DM status was observed at treatment failure. Acquired TB drug resistance was seen in 4 of 18 (22%) in TB-DM vs 4 of 45 (9%) in TB-only (P = .21). Thirteen (17%) participants had exogenous reinfection; the reinfection rate at recurrence was 25% (3/12) for TB-DM vs 17% (4/24) in TB-only (P = .66).
Considerable intrahost Mtb mutation rates were present at recurrence among patients with DM in India. One-fourth of patients with DM had exogenous reinfection at recurrence.
More than 20% of tuberculosis (TB) disease worldwide may be attributable to smoking and alcohol abuse. India is the second largest consumer of tobacco products, a major consumer of alcohol ...particularly among males, and has the highest burden of TB globally. The impact of increasing tobacco dose, relevance of alcohol misuse and past versus current or never smoking status on TB treatment outcomes remain inadequately defined.
We conducted a multi-centric prospective cohort study of newly diagnosed adult pulmonary TB patients initiated on TB treatment and followed for a minimum of 6 months to assess the impact of smoking status with or without alcohol abuse on treatment outcomes. Smokers were defined as never smokers, past smokers or current smokers. Alcohol Use Disorder Identification Test (AUDIT) scores were used to assess alcohol misuse. The association between smoking status and treatment outcomes was assessed in univariate and multivariate random effects poisson regression models.
Of 455 enrolled, 129 (28%) had a history of smoking with 94 (20%) current smokers and 35 (8%) past smokers. Unfavourable treatment outcomes were significantly higher among past and current smokers as compared to never smokers. Specifically, the risk of treatment failure was significantly higher among past smokers (aIRR = 2.66, 95% CI: 1.41-4.90, p = 0.002), recurrent TB among current smokers (aIRR = 2.94, 95% CI: 1.30-6.67, p = 0.010) and death among both past (2.63, 95% CI: 1.11-6.24, p = 0.028) and current (aIRR = 2.59, 95% CI: 1.29-5.18, p = 0.007) smokers. Furthermore, the combined effect of alcohol misuse and smoking on unfavorable treatment outcomes was significantly higher among past smokers (aIRR: 4.67, 95% CI: 2.17-10.02, p<0.001) and current smokers (aIRR: 3.58, 95% CI: 1.89-6.76, p<0.001).
Past and current smoking along with alcohol misuse have combined effects on increasing the risk of unfavourable TB treatment outcomes. Innovative interventions that can readily address both co-morbidities are urgently needed.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Burden, phenotype and risk-factors of lung function defects in successfully treated tuberculosis cases are unclear.
We performed spirometry with bronchodilators in new drug-sensitive adult (≥18 ...years) pulmonary tuberculosis cases during the 12 months following successful treatment in India. Airflow obstruction was defined as pre-bronchodilator FEV1/FVC<5th percentile of Global Lung Initiative mixed-ethnicity reference (lower limit of normal LLN). Chronic obstructive pulmonary disease (COPD) was defined as post-bronchodilator FEV1/FVC<LLN among participants with obstruction. Restrictive spirometry pattern was defined as FVC<LLN among participants without obstruction. Multivariable logistic and linear regression was used to identify risk-factors for obstruction, restriction and low lung function despite successful treatment.
Of the 172 participants included in the analysis, 82 (48%) were female, 22 (13%) had diabetes and 34 (20%) ever-smoked with a median (IQR) exposure of 3.5 (0.2-9.9) pack-years. Median (IQR) age and body-mass index (BMI) at enrollment was 32 (23-39) years and 18.1 (16.0-20.5) kg/m2 respectively. Airflow obstruction was detected in 42 (24%) participants; of whom 9 (21%) responded to short-acting bronchodilators and 25 (56%) had COPD; and was associated with duration of illness prior to treatment (aOR = 1.32 per 30-days, 95%CI 1.04-1.68, p = 0.02). A restrictive spirometry pattern was detected in 89 (52%) participants and was associated with female sex (aOR = 3.73, 95%CI 1.51-9.17, p = 0.004) and diabetes (aOR = 4.06, 95%CI 1.14-14.42, p = 0.03). Higher HbA1c at treatment initiation was associated with greater odds of a restrictive spirometry pattern (aOR = 1.29 per unit higher HbA1c, 95%CI 1.04 to 1.60, p = 0.02).
We found a high burden of lung function defects and COPD in tuberculosis cases who successfully completed treatment. Screening for chronic lung diseases following treatment and linkage to respiratory health clinics should be included in the routine management plan of all tuberculosis cases in India, regardless of conventional COPD risk-factors such as older age and smoking.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pediatric tuberculosis (TB) remains a major global health problem. Improved pediatric diagnostics using readily available biosources are urgently needed. We used liquid chromatography-mass ...spectrometry to analyze plasma metabolite profiles of Indian children with active TB (n = 16) and age- and sex-matched, Mycobacterium tuberculosis-exposed but uninfected household contacts (n = 32). Metabolomic data were integrated with whole blood transcriptomic data for each participant at diagnosis and throughout treatment for drug-susceptible TB. A decision tree algorithm identified 3 metabolites that correctly identified TB status at distinct times during treatment. N-acetylneuraminate achieved an area under the receiver operating characteristic curve (AUC) of 0.66 at diagnosis. Quinolinate achieved an AUC of 0.77 after 1 month of treatment, and pyridoxate achieved an AUC of 0.87 after successful treatment completion. A set of 4 metabolites (gamma-glutamylalanine, gamma-glutamylglycine, glutamine, and pyridoxate) identified treatment response with an AUC of 0.86. Pathway enrichment analyses of these metabolites and corresponding transcriptional data correlated N-acetylneuraminate with immunoregulatory interactions between lymphoid and non-lymphoid cells, and correlated pyridoxate with p53-regulated metabolic genes and mitochondrial translation. Our findings shed new light on metabolic dysregulation in children with TB and pave the way for new diagnostic and treatment response markers in pediatric TB.
World Health Organization (WHO) recommends systematic screening of high-risk populations, including household contacts (HHCs) of adult pulmonary tuberculosis (TB) patients, as a key strategy for ...elimination of TB. QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and tuberculin skin test (TST) are two commonly used tools for the detection of latent tuberculosis infection (LTBI) but may yield differential results, affecting eligibility for TB preventive therapy.
A prospective cohort study of adult pulmonary TB patients and their HHCs were recruited in 2 cities of India, Pune and Chennai. HHCs underwent QFT-GIT (QIAGEN) and TST (PPD SPAN 2TU/5TU). A positive QFT-GIT was defined as value ≥0.35 IU/ml and a positive TST as an induration of ≥5 mm. A secondary outcome of TST induration ≥10mm was explored. Proportion positive by either or both assays, discordant positives and negatives were calculated; test concordance was assessed using percentage agreement and kappa statistics; and risk factors for concordance and discordance including age categories were assessed using logistic regression. Sensitivity and specificity was estimated by latent class model.
Of 1048 HHCs enrolled, 869 median (IQR) age: 27 years (15-40) had both TST and QFT-GIT results available and prevalence of LTBI by QFT-GIT was 54% 95% CI (51, 57), by TST was 55% 95% CI (52, 58), by either test was 74% 95% CI (71, 77) and by both tests was 35% 95% CI (31, 38). Discordance of TST+/QFT-GIT- was 21% while TST-/QFT-GIT+ was 26%. Poor to fair agreement occurred with TST 5mm or 10mm cutoff (60 and 61% agreement with kappa value of 0.20 and 0.25 respectively). Test agreement varied by age, TST strength and induration cut-off. In multivariate analysis, span PPD was a risk factor for QFT-GIT+ and TST- while absence of BCG scar was for TST+ and QFT-GIT-. Being employed and exposure to TB case outside the household case were associated with positivity by both the tests. Sensitivity of TST and QFT-GIT to diagnose LTBI was 77% and 69%. Probability of having LTBI was >90% when both tests were positive irrespective of exposure gradient.
Prevalence of LTBI among HHCs of adult pulmonary TB patients in India is very high and varies by test type, age, and exposure gradient. In our high TB burden setting, a strategy to treat all HHCs or a targeted strategy whereby an exposure index is used should be assessed in future preventive therapy and vaccine studies as HHCs have several factors that place them at high risk for progression to TB disease.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The World Health Organization (WHO) recently changed its guidance for tuberculosis (TB) preventive treatment (TPT) recommending TPT for all pulmonary TB (PTB) exposed household contacts (HHC) to ...prevent incident TB disease (iTBD), regardless of TB infection (TBI) status. However, this recommendation was conditional as the strength of evidence was not strong. We assessed risk factors for iTBD in recently-exposed adult and pediatric Indian HHC, to determine which HHC subgroups might benefit most from TPT. We prospectively enrolled consenting HHC of adult PTB patients in Pune and Chennai, India. They underwent clinical, microbiologic and radiologic screening for TB disease (TBD) and TBI, at enrollment, 4-6, 12 and 24 months. TBI testing was performed by tuberculin skin test (TST) and Quantiferon®- Gold-in-Tube (QGIT) assay. HHC without baseline TBD were followed for development of iTBI and iTBD. Using mixed-effect Poisson regression, we assessed baseline characteristics including TBI status, and incident TBI (iTBI) using several TST and/or QGIT cut-offs, as potential risk factors for iTBD. Of 1051 HHC enrolled, 42 (4%) with baseline TBD and 12 (1%) with no baseline TBI test available, were excluded. Of the remaining 997 HHC, 707 (71%) had baseline TBI (TST #x2265; 5 mm or QGIT #x2265; 0.35 IU/ml). Overall, 20 HHC (2%) developed iTBD (12 cases/1000 person-years, 95%CI: 8-19). HIV infection (aIRR = 29.08, 95% CI: 2.38-355.77, p = 0.01) and undernutrition (aIRR = 6.16, 95% CI: 1.89-20.03, p = 0.003) were independently associated with iTBD. iTBD was not associated with age, diabetes mellitus, smoking, alcohol, and baseline TBI, or iTBI, regardless of TST (#x2265; 5 mm, #x2265; 10 mm, #x2265; 6 mm increase) or QGIT (#x2265; 0.35 IU/ml, #x2265; 0.7 IU/ml) cut-offs. Given the high overall risk of iTBD among recently exposed HHCs, and the lack of association between TBI status and iTBD, our findings support the new WHO recommendation to offer TPT to all HHC of PTB patients residing in a high TB burden country such as India, and do not suggest any benefit of TBI testing at baseline or during follow-up to risk stratify recently-exposed HHC for TPT.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Despite substantial exposure to infectious pulmonary tuberculosis (TB) cases, some household contacts (HHC) never acquire latent TB infection (LTBI). Characterizing these "resisters" can inform who ...to study immunologically for the development of TB vaccines. We enrolled HHCs of culture-confirmed adult pulmonary TB in India who underwent LTBI testing using tuberculin skin test (TST) and QuantiFERON TB Gold Test-in-tube (QFT-GIT) at baseline and, if negative by both (<5mm TST and <0.35IU/mL QFT-GIT), underwent follow-up testing at 4-6 and/or 12 months. We defined persons with persistently negative LTBI tests at both baseline and followup as pLTBI- and resisters as those who had a high exposure to TB using a published score and remained pLTBI-. We calculated the proportion of resisters overall and resisters with complete absence of response to LTBI tests (0mm TST and/or QFT-GIT <0.01 IU/ml). Using random effects Poisson regression, we assessed factors associated with pLTBI-. Of 799 HHCs in 355 households, 67 (8%) were pLTBI- at 12 months; 52 (6.5%) pLTBI- in 39 households were resisters. Complete absence of response to LTBI tests was found in 27 (53%) resisters. No epidemiological characteristics were associated with the pLTBI- phenotype. LTBI free resisters among HHC exist but are uncommon and are without distinguishing epidemiologic characteristics. Assessing the genetic and immunologic features of such resister individuals is likely to elucidate mechanisms of protective immunity to TB.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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