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Gaurav Kaushik,1,2 Richa Vashishtha,2 Chaitenya Verma,3 Shipra Sharma,4 Vinay Kumar5 1School of Allied Health Sciences, Sharda University, Greater Noida, Uttar Pradesh, 201310, India; 2Department of Medicine, All India Institute of Medical Sciences, New Delhi, 110029, India; 3Department of Pathology, Wexner Medical Center, Ohio State University, Columbus, OH, USA; 4Shri Guru Ram Rai Institute of Medical & Health Sciences, Dehradun, Uttarakhand, 248001, India; 5Pennsylvania State University Hershey Medical Center, 500 University Dr, Hershey, PA, 17033, USACorrespondence: Gaurav Kaushik; Vinay Kumar, Email gaurav.kaushik@sharda.ac.in; vinayktyagi07@gmail.comBackground: Toll-like receptors (TLRs) are identified as one of the key components of the innate immune system. The objective of this study was to explore the influence of genetic variability in these TLRs on human immunodeficiency virus (HIV) disease progression with and without tuberculosis (TB) co-infection.Materials and Methods: This prospective, cross-sectional, and longitudinal study included 373 HIV-positive patients without TB infection. This study aimed to examine the genetic variation in TLRs (TLR2, TLR4, and TLR9) between patients with HIV-1 infection and those who progressed to active TB during the two years of follow-up.Results: During the two year follow-up of 373 positive patients, 98 patients progressed to active TB/AIDS (acquired immunodeficiency syndrome). When comparing 98 HIV patients who developed active TB/AIDS to 275 HIV patients who did not, it was discovered that the frequency of the A allele in TLR9 was considerably higher (p < 0.001) in HIV patients progressed to active TB/AIDS. Ninety eight HIV individuals who advanced to active TB/AIDS showed a significantly higher frequency of the AA genotype in TLR9 than did in HIV patients who had no TB/AIDS (p < 0.001).Conclusion: The increased association of the AA genotype of TLR9 in HIV patients who progressed to active TB during follow-up suggests that HIV-positive patients with the AA genotype of TLR9 have increased susceptibility towards TB during the disease progression.Keywords: toll-like receptors, human immunodeficiency virus, tuberculosis, acquired immunodeficiency syndrome, immune system

Background: Alcohol use in early adulthood is a significant public health concern. The prevalence of adolescent alcohol consumption has been declining in high-income English-speaking countries since the early 2000s. This review aims to examine whether this trend continues in young adulthood., Methods: We systematically searched Medline, PsycInfo and CINAHL and the grey literature. Eligible records reported the prevalence of alcohol consumption amongst 18-25-year-olds over a minimum three-year time frame in the United States (US), Canada, the United Kingdom, the Republic of Ireland, Australia and New Zealand. Results were described using narrative synthesis. Quality assessment was undertaken using the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies., Results and Conclusion: Thirty-two records from 22 different surveys were included. The prevalence of consumption amongst young adults fell in Australia, Ireland, and the United Kingdom and was stable in New Zealand and Canada. In the US, there was evidence of a decline in the prevalence of drinking among under-21s, but results for adults over the minimum purchase age were mixed. The prevalence of alcohol consumption in young adults appears to be broadly declining. This could lead to reduced rates of alcohol-related harms in the future. Further high-quality multinational surveys may help to confirm this trend.

Background: Evidence on the comparative performance of purified protein derivative tuberculin skin tests (TST) and interferon-gamma release assays (IGRA) for predicting incident active tuberculosis (TB) remains conflicting. We conducted an individual participant data meta-analysis to directly compare the predictive performance for incident TB disease between TST and IGRA to inform policy., Methods: We searched Medline and Embase from 1 January 2002 to 4 September 2020, and studies that were included in previous systematic reviews. We included prospective longitudinal studies in which participants received both TST and IGRA and estimated performance as hazard ratios (HR) for the development of all diagnoses of TB in participants with dichotomised positive test results compared to negative results, using different thresholds of positivity for TST. Secondary analyses included an evaluation of the impact of background TB incidence. We also estimated the sensitivity and specificity for predicting TB. We explored heterogeneity through pre-defined sub-group analyses (e.g. country-level TB incidence). Publication bias was assessed using funnel plots and Egger's test. This review is registered with PROSPERO, CRD42020205667., Findings: We obtained data from 13 studies out of 40 that were considered eligible (N = 32,034 participants: 36% from countries with TB incidence rate ≥100 per 100,000 population). All reported data on TST and QuantiFERON Gold in-Tube (QFT-GIT). The point estimate for the TST was highest with higher cut-offs for positivity and particularly when stratified by bacillus Calmette-Guérin vaccine (BCG) status (15 mm if BCG vaccinated and 5 mm if not [TST 5/15 mm ]) at 2.88 (95% CI 1.69-4.90). The pooled HR for QFT-GIT was higher than for TST at 4.15 (95% CI 1.97-8.75). The difference was large in countries with TB incidence rate <100 per 100,000 population (HR 10.38, 95% CI 4.17-25.87 for QFT-GIT VS. HR 5.36, 95% CI 3.82-7.51 for TST 5/15 mm ) but much of this difference was driven by a single study (HR 5.13, 95% CI 3.58-7.35 for TST 5/15 mm VS. 7.18, 95% CI 4.48-11.51 for QFT-GIT, when excluding the study, in which all 19 TB cases had positive QFT-GIT results). The comparative performance was similar in the higher burden countries (HR 1.61, 95% CI 1.23-2.10 for QFT-GIT VS. HR 1.72, 95% CI 0.98-3.01 for TST 5/15 mm ). The predictive performance of both tests was higher in countries with TB incidence rate <100 per 100,000 population. In the lower TB incidence countries, the specificity of TST (76% for TST 5/15 mm ) and QFT-GIT (74%) for predicting active TB approached the minimum World Health Organization target (≥75%), but the sensitivity was below the target of ≥75% (63% for TST 5/15 mm and 65% for QFT-GIT). The absolute differences in positive and negative predictive values between TST 15 mm and QFT-GIT were small (positive predictive values 2.74% VS. 2.46%; negative predictive values 99.42% VS. 99.52% in low-incidence countries). Egger's test did not show evidence of publication bias (0.74 for TST 15 mm and p = 0.68 for QFT-GIT)., Interpretation: IGRA appears to have higher predictive performance than the TST in low TB incidence countries, but the difference was driven by a single study. Any advantage in clinical performance may be small, given the numerically similar positive and negative predictive values. Both IGRA and TST had lower performance in countries with high TB incidence. Test choice should be contextual and made considering operational and likely clinical impact of test results., Funding: YH, IA, and MXR were supported by the National Institute for Health and Care Research (NIHR), United Kingdom (RP-PG-0217-20009). MQ was supported by the Medical Research Council [MC&#95;UU&#95;00004/07]., Competing Interests: YH and MXR report donation of QIAreach, an IGRA, by QIAGEN for a LTBI infection survey. YH, MXR, and IA report donations of Cy-TB, a TB-specific skin test for detection of LTBI, by the Serum Institute of India for a study on the feasibility and patient-important outcomes. They had no role in the submitted work. RD declared the receipt of payment for lectures from Qiagen and Oxford Immunotec. JD declared honoraria for lectures from Oxford Immunotec. AG declared receipt of research grants from the US National Institute of Health (NIH) and membership in NIH Council and IndoUS Science Technology Forum. CL provided consultation service to INSMED and received speakers honoraria from INSMED, GILEAD, JANSSEN and is a member of the Data Safety Board of trials from Medicines sans Frontiers, all outside of the submitted work. ILR has a patent (PCT/EP2019/064885), in vitro method for the diagnosis or detection of non-tuberculous mycobacteria. MS reports receipt of test kits free of charge from Qiagen and Oxford Immunotec. MS also reports receipt of research grants from Biotest and Astellas, consulting fees and honoraria from Biotest, Moderna, Qiagen, and Takeda, support for travel from Biotest, and participation on advisory board for Biotest and Moderna, all outside of this work. GS reports receipt of consulting fees from Pfizer, Diasorin, and INSMED. All other authors declare no competing interests., (© 2022 The Author(s).)

Background: It has been demonstrated that toll-like receptors (TLR2), TLR4, and TLR9 which were initially known for recognizing bacterial products are involved in the detection of viral components. It was planned to undertake a prospective longitudinal study among ethnically homogeneous antiretroviral treatment and antitubercular treatment naïve human immunodeficiency virus (HIV)-positive patients representing the north Indian population. The aim of the study was to investigate the influence of TLR2, TLR4, and TLR9 polymorphism in HIV disease progression., Methods: The present study was designed to investigate genetic polymorphism in TLRs (TLR2, TLR4, and TLR9) among HIV-infected patients with and without TB coinfection. The study population consisted of two groups: (i) HIV-positive patients without TB infection and disease (n = 223, HIV-positive patients); (ii) HIV-positive patients with latent tuberculosis infection (LTBI) (n = 150, HIV-positive LTBI patients). These participants were of either gender between 18 and 60 years of age and treatment naïve for both TB and HIV. HIV-positive and HIV-positive LTBI patients were longitudinally followed up for t2 years to study HIV disease progression., Results: On comparing TLR2 and TLR4 allelic and genotypic frequencies between 306 HIV-positive patients (no TB/AIDS) and 47 HIV-positive patients progressed to active TB/AIDS, no significant difference was observed between the two groups. The frequency of "A" allele in TLR9 was found to be significantly increased in 47 HIV-positive patients who progressed to active TB/AIDS (61.7%) as compared to 42.16% in 306 HIV-positive patients (no TB/AIDS), (P < 0.001). Furthermore, a significantly increased frequency of "AA" genotype in TLR9 was observed in 47 HIV-positive patients progressed to active TB/AIDS (55.32%) as compared to 20.26% in HIV-positive patients (no TB/AIDS)., Conclusion: Findings of the present study revealed that genetic variability in TLR9 may influence HIV disease progression. The AA genotype in TLR9 may be associated with progression to TB/AIDS for 2 years in HIV-positive patients., Competing Interests: None

Background: BCG vaccines are given to more than 100 million children every year, but there is considerable debate regarding the effectiveness of BCG vaccination in preventing tuberculosis and death, particularly among older children and adults. We therefore aimed to investigate the age-specific impact of infant BCG vaccination on tuberculosis (pulmonary and extrapulmonary) development and mortality., Methods: In this systematic review and individual participant data meta-analysis, we searched MEDLINE, Web of Science, BIOSIS, and Embase without language restrictions for case-contact cohort studies of tuberculosis contacts published between Jan 1, 1998, and April 7, 2018. Search terms included "mycobacterium tuberculosis", "TB", "tuberculosis", and "contact". We excluded cohort studies that did not provide information on BCG vaccination or were done in countries that did not recommend BCG vaccination at birth. Individual-level participant data for a prespecified list of variables, including the characteristics of the exposed participant (contact), the index case, and the environment, were requested from authors of all eligible studies. Our primary outcome was a composite of prevalent (diagnosed at or within 90 days of baseline) and incident (diagnosed more than 90 days after baseline) tuberculosis in contacts exposed to tuberculosis. Secondary outcomes were pulmonary tuberculosis, extrapulmonary tuberculosis, and mortality. We derived adjusted odds ratios (aORs) using mixed-effects, binary, multivariable logistic regression analyses with study-level random effects, adjusting for the variable of interest, baseline age, sex, previous tuberculosis, and whether data were collected prospectively or retrospectively. We stratified our results by contact age and Mycobacterium tuberculosis infection status. This study is registered with PROSPERO, CRD42020180512., Findings: We identified 14 927 original records from our database searches. We included participant-level data from 26 cohort studies done in 17 countries in our meta-analysis. Among 68 552 participants, 1782 (2·6%) developed tuberculosis (1309 [2·6%] of 49 686 BCG-vaccinated participants vs 473 [2·5%] of 18 866 unvaccinated participants). The overall effectiveness of BCG vaccination against all tuberculosis was 18% (aOR 0·82, 95% CI 0·74-0·91). When stratified by age, BCG vaccination only significantly protected against all tuberculosis in children younger than 5 years (aOR 0·63, 95% CI 0·49-0·81). Among contacts with a positive tuberculin skin test or IFNγ release assay, BCG vaccination significantly protected against tuberculosis among all participants (aOR 0·81, 95% CI 0·69-0·96), participants younger than 5 years (0·68, 0·47-0·97), and participants aged 5-9 years (0·62, 0·38-0·99). There was no protective effect among those with negative tests, unless they were younger than 5 years (0·54, 0·32-0·90). 14 cohorts reported on whether tuberculosis was pulmonary or extrapulmonary (n=57 421). BCG vaccination significantly protected against pulmonary tuberculosis among all participants (916 [2·2%] in 41 119 vaccinated participants vs 334 [2·1%] in 16 161 unvaccinated participants; aOR 0·81, 0·70-0·94) but not against extrapulmonary tuberculosis (106 [0·3%] in 40 318 vaccinated participants vs 38 [0·2%] in 15 865 unvaccinated participants; 0·96, 0·65-1·41). In the four studies with mortality data, BCG vaccination was significantly protective against death (0·25, 0·13-0·49)., Interpretation: Our results suggest that BCG vaccination at birth is effective at preventing tuberculosis in young children but is ineffective in adolescents and adults. Immunoprotection therefore needs to be boosted in older populations., Funding: National Institutes of Health., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Adolescent drinking has declined in many high-income countries since the early 2000s. It has been suggested that changing parenting practices may have contributed to the decline. However, previous studies investigating parenting have focused on single countries and have provided conflicting evidence. This study tested the association between changes in individual- and population-level parental control and parental support and changes in past month adolescent drinking., Methods: A total of 271,823 adolescents aged 15-16 years, from 30 European countries between 2003 and 2015 were included in this study. Our key independent variables were adolescent reports of parental control and parental support. Our outcome measure was a dichotomous measure of any alcohol use in the 30 days before the survey, referred as past month drinking. Aggregated measures of parenting variables were used to estimate between-country and within-country effects of parenting on adolescent drinking. Data were analysed using three-level hierarchical linear probability methods., Results: At the individual-level, we found a negative association between the two parental measures, i.e. parental control (β = -0.003 and 95% CI = -0.021 to 0.017) and parental support (β = -0.008 and 95% CI = -0.010 to 0.006) and past month drinking. This suggests adolescents whose parents exert higher control and provide more support tend to drink less. At a population level, we did not find any evidence of association on between-country and within-country parenting changes and past month drinking., Conclusions: It is unlikely that changes in parental control or support at the population-level have contributed to the decline in drinking among adolescents in 30 European countries., (© The Author(s) 2022. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Background: Gene expression levels of TLRs (TLR2, TLR4 and TLR9) are directly involved in the virus recognition and initiation of innate immune responses, therefore, the effect of HIV infection on TLRs gene expression was investigated in functional context through mRNA levels estimations of selected TLRs., Methods: In the present study mRNA gene expression of TLR2, TLR4 and TLR9 has been investigated in HIV+ and HIV+TB patients and compared with healthy subjects., Result: The increase expression of TLR2, TLR4 and TLR9 (mRNA level) relative to the internal gene GAPDH was observed in HIV+ and HIV+TB patients as compared to healthy subjects. Similarly, increase in TLRs mRNA expression was observed in HIV+TB patients as compared to HIV+ patients., Conclusion: A modest increase in expression of TLRs in HIV+ patients with and without TB co-infection suggest a potential role for these TLRs in HIV-1 immunopathogenesis., Competing Interests: None

Background: Changes in adolescents' attitudes towards school are a potential explanation for recent declines in young people's alcohol consumption. However, this has not been tested using multi-national survey data, which would permit stronger causal inferences by ruling out other country-specific explanations. This study, therefore, uses an international survey of schoolchildren to examine the associations between changing attitudes towards school and adolescent alcohol consumption., Methods: We used data from 247 325 15-year-olds across 37 countries participating in four waves of the Health Behaviour in School-aged Children study (2001/02-2013/14). Attitudes towards school were assessed using two measures-self-reported pressure from schoolwork and whether respondents like school. Outcome measures were weekly alcohol consumption and having been drunk twice in one's lifetime. We used whole population and gender-specific hierarchical linear probability models to assess the relationship between attitudes and alcohol outcomes within countries over time., Results: Country-level changes over time in liking school were not associated with changes in alcohol consumption. However, a 10% increase in feeling pressured by schoolwork was associated with a 1.8% decline in drunkenness [95% confidence interval (CI): -3.2% to -0.3%] and weakly associated with a 1.7% decline in weekly drinking (95% CI: -3.6% to 0.2%). Among girls only, increases in feeling pressured by schoolwork were associated with a 2.1% decline in weekly drinking (95% CI: -3.7% to -0.6%) and a 2.4% decline in drunkenness (95% CI: -3.8% to -1.1%)., Conclusion: Changes in attitudes towards school may have played a minor role in the decline in alcohol consumption among adolescent girls only., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Public Health Association.)

Background and Aims: Adolescent drinking in Australia (and many other countries) has declined substantially since the early 2000s. This study aimed to test whether these declines have been maintained into adulthood and whether they are consistent across sub-groups defined by sex and socio-economic status., Design: Quasi-cohorts were constructed from seven repeated waves of cross-sectional household survey data (2001-2019)., Setting: Australia., Participants: A total of 20 733 respondents age between 14 and 24 (male: 9492; female: 11 241)., Measurements: Participants were grouped into five cohorts based on their birth year (from 1979-1983 to 1999-2003). Three measures of drinking were assessed: any past-year consumption (yes/no), past-year regular risky drinking (12 or more drinking episodes of >40 g of pure alcohol, yes/no) and total volume of alcohol consumed in the past year (in Australian standard drinks, 10 g of alcohol). Socio-economic status was measured based on neighbourhood of residence., Findings: Drinking declines were consistent across socio-economic groups on all measures and trends were broadly similar for women and men. More recent birth cohorts had significantly lower levels of drinking across all three measures (odds ratios between 0.31 and 0.70 for drinking and risky drinking, coefficients between -0.28 and -0.80 for drinking volume). There were significant interactions between birth cohort and age for past-year drinking and past-year regular risky drinking, with cohort differences diminishing as age increased., Conclusions: Lighter drinking adolescent cohorts appear to partly 'catch up' to previous cohorts by early adulthood, but maintain lower levels of drinking and risky drinking up to the age of 24. These ongoing reductions in drinking are spread evenly across socio-economic groups., (© 2021 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: In the early 2000s, alcohol use among young people began to decline in many western countries, especially among adolescents (ages between 12-17 years old). These declines have continued steadily over the past two decades, against the backdrop of much smaller declines among the general population., Argument: Hypotheses examining individual factors fail adequately to provide the necessary 'big picture' thinking needed to understand declines in adolescent drinking. We use the normalisation thesis to argue that there is strong international evidence for both processes of denormalisation of drinking and normalisation of non-drinking occurring for adolescents in many western countries., Conclusions: Research on declining adolescent drinking provides evidence of both denormalisation of alcohol consumption and normalisation of non-drinking. This has implications for enabling policy environments more amenable to regulation and increasing the acceptability of non-drinking in social contexts. Normalisation theory (and its various interpretations) provides a useful multi-dimensional tool for understanding declines in adolescent drinking., (© 2021 Society for the Study of Addiction.)

Introduction: Adolescent alcohol consumption has been declining in many high-income countries since the turn of this century. Research investigating the plausible explanations for these declines has been mostly based on individual-level studies, which are largely inconclusive. Changes in leisure time internet use and computer gaming (referred to in this article as 'computer activities') have been hypothesised to play a role in declining adolescent alcohol consumption at a country-level. The aim of this study was to examine the association between country-level changes over time in computer activities and adolescent drinking in 33 European countries., Methods: This is a multi-level repeated cross-national study examining the role of changes over time in country-level and individual-level computer activities on regular drinking. We utilised four waves of the European School Survey Project on Alcohol and Drugs (ESPAD) from 2003, 2007, 2011 and 2015. At an individual-level the primary exposure of interest was daily engagement in computer activities and aggregated means were used to measure country-level daily computer activities in each included country. Data were analysed using three-level hierarchical linear probability methods., Results: In the fully adjusted model, for between individual effects, we found significant positive association between daily computer activities and regular drinking (β = 0.043, p-value <0.001 and 95% CI = 0.033-0.054). However, at a country-level, we did not find any association between within-country changes in daily computer activities and regular drinking (β = 0.031, p-value = 0.652 and 95% CI = -0.103-0.164., Conclusion: Findings from this study suggest that broad cultural shifts towards increased computer-based activities among adolescents has played a little or no role in declining adolescent drinking. Future research should be directed towards examining other high-level cultural changes which may have influenced cross-national reductions in adolescent drinking., Competing Interests: Declarations of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The news media can reflect and influence public opinion, as well as affect individual practice. In the context of significant changes in alcohol consumption among young people over the past twenty years, we examined Australian newspaper reporting of young people (under 18 years) and alcohol to assess whether there have been changes over time in the content and slant of articles that reflect or elucidate these trends., Methods: Factiva was used to search newspaper articles from major Australian newspapers over a twenty year period (2000-2019). After screening, two researchers coded 2415 newspaper articles across four key domains: article type, article theme, sources cited and topic slant (e.g. approving, disapproving tone). Change over time across the study period was assessed using joinpoint Poisson regression analyses., Results: There was a significant increase in articles on young people and alcohol between 2000 and 2008, before a corresponding decrease to 2019. Policy or prevention strategies were the most common theme of articles (35.8%), followed by articles reporting on risks or harms associated with alcohol use for young people (18.1%). Researchers were the most common source reported (25.1%), followed by politicians (19.0%). Three quarters of articles (75.9%) had a socially disapproving topic slant, which increased significantly up until 2011, with a corresponding decrease thereafter., Conclusion: Attention to, and problematisation of, young people and alcohol increased in the first decade of this millennium which may have acted to sustain or accelerate declining drinking trends. However, this dissipated back to baseline levels in the second decade, which may indicate a lag time in recognition of young people's drinking becoming less of a public health 'problem'., Competing Interests: Declarations of Interest None., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Toll-like receptors (TLRs) are identified as one of the key components of innate immune system due to their ability to sense conserved molecular motifs associated with several pathogens. It has been implicated from several evidence that mutations in genes encoding TLRs are associated with increased or decreased susceptibility to various infectious diseases., Methods: The study was prospective, cross-sectional, as well as longitudinal in nature, which includes 223 HIV-positive patients, 150 HIV-positive patients with latent tuberculosis (TB) infection, 150 HIV-positive patients with active TB, 200 HIV-negative newly diagnosed sputum smear positive pulmonary TB patients, and 205 healthy subjects., Results: A statistically significant difference was observed in allelic frequencies of TLR4 between healthy subjects and HIV + TB patients (P < 0.001), healthy subjects, and pulmonary TB (PTB) Category-I patients (P < 0.01) and between healthy subjects and HIV + TB patients (P < 0.001). TLR4 genotype frequencies were also significantly different between healthy subjects and PTB Cat I patients (P < 0.001) and HIV + and HIV + TB patients (P < 0.01). A statistically significant difference was also observed between HIV + and PTB Cat I patients (P = 0.04), HIV + LTBI and HIV + TB patients (P = 0.01), and between HIV + TB and PTB Cat I patients (P < 0.01)., Conclusion: This study implicates that Asp299Gly polymorphism in TLR4 gene is associated with increased susceptibility to active TB in HIV-seropositive patients. Increased frequency of 'A' allele in TLR9 gene was also discovered at the time of active TB development in ART naïve HIV + patients, who developed active TB on follow-up., Competing Interests: None

Introduction: Adolescent drinking has been declining in Australia over the past two decades, but this trend may be part of a broader shift towards healthier lifestyles for adolescents. We examined trends in the prevalence of multiple risky health- and school-related behaviours and outcomes to test whether this was the case., Methods: Data on multiple behaviours and outcomes were collated from Australian government agencies and other relevant sources for 10-19-year-olds from the year 2000 onward. Trends were examined descriptively., Results: Rates of substance use, youth offending and injuries due to underage driving declined over the study period. Some health-related behaviours (physical activity and diet) worsened between 2001 and 2017; however, obesity rates remained stable. Risky sexual behaviours increased in terms of early initiation of lifetime sexual intercourse and decreased condom use. However, sexual health outcomes improved with a reduction in teenage pregnancies and there was a recent decline in sexually transmitted infection rates from 2011 onward. Suicide rates and rates of major depressive disorders increased. School attendance and engagement in full-time work or study remained stable., Discussion and Conclusions: The decline in adolescent drinking does not appear to correspond with increased engagement in healthier behaviours; however, it may be related to a more risk-averse way of living. Future work could be directed towards identifying which social, economic, policy and environmental factors have impacted positive changes in risky behaviours. Public health efforts can then be directed towards behaviours or outcomes, which have not yet improved., (© 2021 Australasian Professional Society on Alcohol and other Drugs.)

Background: Evidence suggests adolescent alcohol consumption has declined since the turn of the millennium in almost all high-income countries. However, differences in the timing and magnitude of the decline have not been explored across countries., Methods: We examined trends in adolescent past month or monthly alcohol consumption prevalence from cross-national or national survey reports for 39 countries and four US territories. For each country, we calculated the magnitude of the decline in youth drinking as the relative change in prevalence from the peak year to the most recent year available. Heat maps were utilized to present the timing and magnitudes of these declines., Results: The timing and extent of youth drinking declines have varied markedly across countries. The decline began in the USA before 1999, followed by Northern European countries in the early 2000s; Western Europe and Australasia in the mid-2000s. The steepest declines were found for Northern Europe and the UK, and the shallowest declines were observed in Eastern and Southern European countries., Conclusions: Previous analyses of the decline in adolescent drinking have emphasized the wide reach of the changes and their near-coincidence in time. Our analysis points to the other side of the picture that there were limits to the wide reach, and that there was considerable variation in timing. These findings suggest that as well as broader explanations that stretch across countries, efforts to explain recent trends in adolescent drinking should also consider factors specific to countries and regions., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Objective: To systematically review the evidence for the efficacy of mesenchymal stem cell (MSC) injections in improving osteoarthritis (OA)-related structural outcomes., Methods: Ovid Medline and EMBASE were searched from their inceptions to April 2020 using MeSH terms and key words. Independent reviewers extracted data and assessed methodological quality. Qualitative evidence synthesis was performed due to the heterogeneity of interventions and outcome measures., Results: Thirteen randomized controlled trials (phase I or II) were identified: 10 in OA populations and 3 in populations at risk of OA, with low (n = 9), moderate (n = 3), or high (n = 1) risk of bias. Seven studies used allogeneic MSCs (4 bone marrow, 1 umbilical cord, 1 placenta, 1 adipose tissue), 6 studies used autologous MSCs (3 adipose tissue, 2 bone marrow, 1 peripheral blood). Among the 11 studies examining cartilage outcomes, 10 found a benefit of MSCs on cartilage volume, morphology, quality, regeneration, and repair, assessed by magnetic resonance imaging, arthroscopy, or histology. The evidence for subchondral bone was consistent in all 3 studies in populations at risk of OA, showing beneficial effects. Sixteen unpublished, eligible trials were identified by searching trial registries, including 8 with actual or estimated completion dates before 2016., Conclusion: Our systematic review of early-phase clinical trials demonstrated consistent evidence of a beneficial effect of intraarticular MSC injections on articular cartilage and subchondral bone. Due to the heterogeneity of MSCs, modest sample sizes, methodological limitations, and potential for publication bias, further work is needed before this therapy is recommended in the management of OA., (Copyright © 2021 by the Journal of Rheumatology.)

We provide the South Asian Declaration, containing the consensus guidelines for coronavirus disease 2019 (COVID-19) vaccination in cancer patients., Competing Interests: Conflict of Interest None declared., (MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Objective: Adolescent alcohol consumption has declined in Australia over the past 20 years. Secondary supply laws (SSLs) typically prohibit the supply of alcohol to adolescents by persons other than parents or guardians, or without parental consent. SSLs were introduced in Australia at different times in different states and territories over the period of declining alcohol consumption. In this study we examined the impact of variations in SSLs across Australia on young people's drinking., Method: We used six waves of the National Drug Strategy Household Survey, a cross-sectional survey of the Australian population, from 2001 to 2016. The study population was adolescents ages 14-17 years. Our primary measure of interest was exposure to SSLs. Data were analyzed using two-way linear and logistic regression models with fixed effects of Australian state/territory and time to identify the effect of SSLs on the frequency of drinking, past-year drinking, and the secondary supply source, respectively., Results: We found no evidence of an association between SSLs and any of the three outcomes of interest., Conclusions: SSLs are challenging to enforce, and, although they may empower parents to have more control over their children's drinking, they were not associated with reductions in adolescent drinking in Australia. Researchers looking to explain the decline in adolescent drinking in Australia should investigate factors beyond SSLs., Competing Interests: Paul Dietze has received investigator-initiated funding from Gilead Sciences and an untied educational grant from Indivior. He is also an unpaid member of an advisory board for Mundipharma for work unrelated to this study.

Background: Recent analyses of data from the US found that young people were increasingly engaging in cannabis use before alcohol and cigarettes. These shifts are important for public health, but it is not clear whether such trends extend beyond the US. The aim of this study is to examine whether and how the age and sequencing of initiation into alcohol, cannabis and cigarette use has changed in Australia since the early 2000s., Methods: Data came from six waves of the Australian National Drug Strategy Household Survey, spanning 2001-2016. We used data from 18 to 21 year-olds (n = 6849) and examined trends in the age at first use for each of the three substances plus any changes in the order of initiation., Results: The mean age of initiation increased steadily for all three substances (e.g. from 14.9 in 2001 to 16.4 in 2016 for alcohol), while the prevalence of any use declined. There were some changes in ordering of use. For example, in 2001, 62 % of respondents who used both cigarettes and cannabis had first used cigarettes at an earlier age than cannabis, compared with 41 % in 2016. Young people who used both alcohol and cannabis remained more likely to try alcohol before cannabis across the study period., Conclusions: Our results partly replicated US findings, with differences potentially reflecting the substantially different environment around these substances in the US compared to Australia. The age of initiation for alcohol, cigarette and cannabis use in Australia has increased sharply over the past 15 years., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aim: Some children's special health-care needs (SHCN) are formalised at the start of schooling (established SHCN), but a larger proportion start with difficulties that are milder or not yet diagnosed (emerging SHCN). This study explores whether: (i) the prevalence of teacher-identified SHCN (both overall and according to type of needs) and (ii) distribution across disadvantaged communities have changed over three successive population cohorts of Australian children., Methods: We draw on repeated cross-sectional data from the Australian Early Development Census, a teacher-reported checklist completed on full populations of Australian school entrants in 2009, 2012 and 2015. It includes a measure of SHCN, as well as demographic information., Results: The proportion of children with emerging and established needs was mostly stable from 2009 to 2015 (emerging needs: 17.1-18.9%; established needs: 4.4-4.9%). Change over time was observed in the prevalence of some specific types of impairment. Speech impairment rose by 14.7% for children with emerging needs, and emotional problems rose by 13.7% for children with established needs. Children living in the most disadvantaged neighbourhoods had higher odds of SHCN in all years (e.g. emerging needs relative risk ratio 1.65 (99% confidence interval 1.55-1.75) in 2015; established needs relative risk ratio 1.88 (99% confidence interval 1.71-2.06) in 2015)., Conclusions: A large proportion of children starting school each year have SHCN. The types of SHCN that children present with increasingly reflect complex difficulties that require input from both the health and education sectors. Effective responses also need to consider the added impact of disadvantage., (© 2018 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background: There are currently two tests for diagnosing latent tuberculosis infection (LTBI); TST and IGRA. However, it is still unclear that which one of these tests performs better in high TB-burden settings., Methods: 1511 household contacts of pulmonary TB patients were enrolled to compare the performance of TST and IGRA for LTBI. At baseline all participant underwent testing for IGRA [QuantiFERON-TB® Gold In-tube (QFT-GIT) assay] and TST [2 tuberculin unit (TU), purified protein derivative (PPD), RT23, Staten Serum Institute (SSI), Copenhagen, Denmark]. All the household contacts were followed-up for two years for incident TB cases., Results: Active TB was diagnosed in 76 household contacts at an incidence rate of 2.14 per 1000 person-years. Both, TST [Hazard Ratio (HR): 1.14, 95% confidence interval (CI): 0.72-1.79, p = 0.57], as well as QFT-GIT assay (HR: 1.66, 95% CI: 0.97-2.84, p = 0.06) results at baseline were not significantly associated with subsequent development of active TB among household contacts of pulmonary TB patients., Conclusion: Neither TST nor IGRA predicted subsequent development of active TB among household contacts of pulmonary TB patients during follow-up. However, keeping in view the cost, and other logistics, TST remains the most preferred method for LTBI diagnosis in resource-limited, high TB-burden settings., Competing Interests: The authors have declared that no competing interests exist.

Background: Despite the latest World Health Organization guidelines advocating daily therapy in HIV-TB co-infected individuals, there are few recent studies comparing outcomes of thrice-weekly anti-tuberculosis treatment in HIV-positive and HIV-negative patients with TB. The present study sets out to compare TB treatment outcomes in these two groups in the Indian national programme, which currently involves thrice-weekly therapy for all, regardless of HIV status., Methods: HIV-positive and HIV-negative were consecutively screened for enrolment into this prospective observational study, carried out at the All India Institute of Medical Sciences hospital, New Delhi, India, between 2006 and 2010. Patients were given short-course thrice-weekly rifampicin-based therapy, with all HIV-positive patients being started on highly active antiretroviral therapy at least 14 days after commencing TB treatment. Patients were regularly followed-up for 24 months after completion of treatment., Results: 150 HIV-positive, 155 HIV-negative patients were enrolled consecutively for the study. Significantly higher treatment success (93.5% vs. 76.7% at end of treatment, p < 0.001) and lower mortality (2.8% vs. 21.6% on follow up, p < 0.001) were observed in HIV-negative patients. No significant difference was found in treatment failure (p = 0.16), sputum smear (p = 0.58) and culture conversion (p = 0.55), and non-serious adverse event incidence (p = 0.851) between the two groups. Low baseline CD4 cell count (<100 cells/ mm3) was the only predictor of mortality in HIV-TB patients (odds ratio 8 · 43, p = 0 · 013)., Conclusions: Thrice-weekly anti-tuberculosis therapy is more effective in HIV-negative than in HIV-positive patients. However, outcomes in this HIV co-infected cohort were found to be similar to those reported previously with daily therapy, with no safety concerns. This should prompt further study into whether intermittent or daily therapy should be used universally in resource-poor settings, using large well executed randomised controlled trials., Trial Registration: NCT No. 00698334.

Background & Objective: IRIS is an important complication that occurs during management of HIV-TB coinfection and it poses difficulty in diagnosis. Previous studies have reported variable incidence of IRIS. The present study was undertaken to describe the pattern of TB-associated IRIS using recently proposed consensus case-definitions for TB-IRIS for its use in resource-limited settings., Methods: A prospective analysis of ART-naïve adults started on HAART from November, 2008 to May, 2010 was done in a tertiary care hospital in north India. A total 224 patients divided into two groups, one with HIV-TB and the other with HIV alone, were followedup for a minimum period of 3 months. The diagnosis of TB was categorised as ''definitive" and ''probable"., Results: Out of a total of 224 patients, 203 completed followup. Paradoxical TB-IRIS occurred in 5 of 123 (4%) HIV-TB patients while 6 of 80 (7.5%) HIV patients developed ART-associated TB. A reduction in plasma viral load was significantly (P = .016) associated with paradoxical TB-IRIS. No identifiable risk factors were associated with the development of ART-associated TB., Conclusion: The consensus case-definitions are useful tools in the diagnosis of TB-associated IRIS. High index of clinical suspicion is required for an early diagnosis.