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: Introduction: The clinical relevance of low‐level viraemia (LLV) and virological outcomes among children living with HIV (CLHIV) remains controversial. This study aimed to determine the impact of LLV on virological failure (VF) among Asian CLHIV on first‐line combination antiretroviral therapy (cART). Methods: CLHIV aged 14 days, or received treatment and care at sites with a pVL lower limit of detection >50 copies/mL were excluded. LLV was defined as a pVL 50 to 1000 copies/mL, and VF as a single pVL >1000 copies/mL. Baseline was the time of the second pVL < 50 copies/mL. Cox proportional hazards models were performed to assess the association between LLV and VF. Results: From January 2008 to September 2016, 508 CLHIV (55% female) were eligible for the study. At baseline, the median age was 9.6 (IQR: 7.0 to 12.3) years, cART duration was 1.4 (IQR: 1.3 to 1.8) years, 97% of CLHIV were on non‐nucleoside reverse transcriptase inhibitor‐based regimens, and the median CD4 was 25% (IQR: 20% to 30%). Over a median follow‐up time of 6.0 (IQR: 3.1 to 8.9) years from baseline, 86 CLHIV (17%) had ever experienced LLV, of whom 32 (37%) had multiple LLV episodes. Female sex, living in Malaysia (compared to Cambodia), having family members other than biological parents/grandparents as a primary caregiver, and baseline CD4 < 25% increased risk of LLV. Overall, 115 children (23%) developed VF, corresponding to a rate of 4.0 (95%CI: 3.4 to 4.9) per 100 person‐years of follow‐up (PYFU). VF was greater among children who had ever experienced LLV compared with those who maintained virological suppression throughout the study period (8.9 vs. 3.3 per 100 PYFU; p < 0.001). In multivariable analyses, ever experiencing LLV was associated with increased risk of subsequent VF (adjusted hazard ratio: 3.01; 95%CI: 1.97 to 4.60). Conclusions: LLV increased the risk of subsequent VF among Asian CLHIV who had previously been suppressed on first‐line cART. Adherence interventions and additional targeted pVL monitoring may be warranted among children with LLV to facilitate early detection of VF., INTRODUCTION HIV plasma viral load (pVL) is an important tool to monitor treatment response and assess medication adherence in people living with HIV. One of the primary aims of combination [...]

Describes a case of Lemierre syndrome due to non-multiresistant methicillin-resistant Staphylococcus aureus. Case background; Septic thrombophlebitis; Bone or joint infection and visceral abscessesin the liver or spleen.

Despite significant global reductions in cases of pneumonia during the last 3 decades, pneumonia remains the leading cause of post-neonatal mortality in children aged <5 years. Beyond the immediate disease burden it imposes, pneumonia contributes to long-term morbidity, including lung function deficits and bronchiectasis. Viruses are the most common cause of childhood pneumonia, but bacteria also play a crucial role. However, the optimal duration of antibiotic therapy for bacterial pneumonia remains uncertain in both low- and middle-income countries and in high-income countries. Knowing the optimal duration of antibiotic therapy for pneumonia is crucial for effective antimicrobial stewardship. This is especially important as concerns mount over rising antibiotic resistance in respiratory bacterial pathogens, which increases the risk of treatment failure. Numerous studies have focused on the duration of oral antibiotics and short-term outcomes, such as clinical cure and mortality. In contrast, only one study has examined both intravenous and oral antibiotics and their impact on long-term respiratory outcomes following pneumonia hospitalisation. However, study findings may be influenced by their inclusion criteria when children unlikely to have bacterial pneumonia are included. Efforts to differentiate between bacterial and non-bacterial pneumonia continue, but a validated, accurate, and simple point-of-care diagnostic test remains elusive. Without certainty that a child has bacterial pneumonia, determining the optimal duration of antibiotic treatment is challenging. This review examines the evidence for the recommended duration of antibiotics for treating uncomplicated pneumonia in otherwise healthy children and concludes that the question of duration is unresolved., Competing Interests: Declarations. Conflict of Interest: ABC, GBM, STY, and KG have received grants from the Australian National Health and Medical Research Council (NHMRC) and NHMRC-managed grants (Medical Research Futures Fund). ABC is also an independent data management committee member for clinical trials for Moderna (COVID-19 and Epstein-Barr virus vaccines) and of an unlicensed vaccine (GlaxoSmithKline) and monoclonal antibody (AstraZeneca) and has received fees to the institution for consulting on the study designs for Zambon and Boehringer Ingelheim, airfares for travel from the European Respiratory Society and Boehringer Ingelheim, and personal fees for being an author of two UpToDate chapters that are outside the submitted work. HCK and SMF have no conflicts of interest to disclose. Funding: Open access funding enabled and organized by CAUL and its Member Institutions. No funds, grants, or other support were received during the preparation of this manuscript. HCK is supported by the Malaysian Ministry of Health and a Charles Darwin International PhD Scholars scholarship, and ABC is supported by an NHMRC L3 fellowship (grant 2025379). Ethics Approval: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Availability of Data and Material: Not applicable. Code Availability: Not applicable. Author Contributions: HCK wrote the first draft of the manuscript, with revisions from KG and ABC. All authors contributed to editing the manuscript and approved the final version., (© 2025. The Author(s).)

Background: Pediatric community-acquired pneumonia (CAP) can lead to long-term respiratory sequelae, including bronchiectasis. We determined if an extended (13-14 days) versus standard (5-6 days) antibiotic course improves long-term outcomes in children hospitalized with CAP from populations at high risk of chronic respiratory disease., Methods: We undertook a multicenter, double-blind, superiority, randomized controlled trial involving 7 Australian, New Zealand, and Malaysian hospitals. Children aged 3 months to ≤5 years hospitalized with radiographic-confirmed CAP who received 1-3 days of intravenous antibiotics, then 3 days of oral amoxicillin-clavulanate, were randomized to either extended-course (8-day oral amoxicillin-clavulanate) or standard-course (8-day oral placebo) arms. Children were reviewed at 12 and 24 months. The primary outcome was children with the composite endpoint of chronic respiratory symptoms/signs (chronic cough at 12 and 24 months; ≥1 subsequent hospitalized acute lower respiratory infection by 24 months; or persistent and/or new chest radiographic signs at 12-months) at 24-months postdischarge, analyzed by intention-to-treat, where children with incomplete follow-up were assumed to have chronic respiratory symptoms/signs ("worst-case" scenario)., Results: A total of 324 children were randomized [extended-course (n = 163), standard-course (n = 161)]. For our primary outcome, chronic respiratory symptoms/signs occurred in 97/163 (60%) and 94/161 (58%) children in the extended-courses and standard-courses, respectively [relative risk (RR) = 1.02, 95% confidence interval (CI): 0.85-1.22]. Among children where all sub-composite outcomes were known, chronic respiratory symptoms/signs between groups, RR = 1.10, 95% CI: 0.69-1.76 [extended-course = 27/93 (29%) and standard-course = 24/91 (26%)]. Additional sensitivity analyses also revealed no between-group differences., Conclusion: Among children from high-risk populations hospitalized with CAP, 13-14 days of antibiotics (versus 5-6 days), did not improve long-term respiratory outcomes., Competing Interests: A.B.C., K.G., S.T.Y., R.S.W., G.B.M., P.S.M., J.W.U., and P.J.T. report grants from NHMRC and NHMRC-managed grants (Medical Research Futures Fund), during the conduct of the study. ABC is also an independent data management committee member for clinical trials for Moderna (COVID-19 and EBV vaccines) and of an unlicensed vaccine (GlaxoSmithKline) and monoclonal antibody (AstraZeneca), received fees from the institution for consulting on the study designs for Zambon and Boehringer Ingelheim, airfares for travel from the European Respiratory Society and Boehringer Ingelheim, and personal fees for being an author of two UpToDate chapters that are outside the submitted work. The other authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Disclosure of HIV status is an important part of pediatric care. We studied disclosure and clinical outcomes in a multi-country Asian cohort of children and adolescents with HIV. Those 6-19 years of age who initiated combination antiretroviral therapy (cART) between 2008 and 2018, and who had at least one follow-up clinic visit were included. Data up to December 2019 were analyzed. Cox and competing risk regression analyses were used to assess the effect of disclosure on disease progression (WHO clinical stage 3 or 4), loss to follow-up (LTFU; > 12 months), and death. Of 1913 children and adolescents (48% female; median [IQR] age 11.5 [9.2-14.7] years at last clinic visit), 795 (42%) were disclosed to about their HIV status at a median age of 12.9 years (IQR: 11.8-14.1). During follow-up, 207 (11%) experienced disease progression, 75 (3.9%) were LTFU, and 59 (3.1%) died. There were lower hazards of disease progression (adjusted hazard ratio [aHR] 0.43 [0.28-0.66]) and death (aHR 0.36 [0.17-0.79]) for those disclosed to compared with those who were not. Disclosure and its appropriate implementation should be promoted in pediatric HIV clinics in resource-limited settings.

Despite improvements in HIV testing and earlier antiretroviral therapy (ART) initiation in children living with HIV through the years, a considerable proportion start treatment with advanced disease. We studied characteristics of children and adolescents living with HIV and their level of immunodeficiency at ART initiation using data from a multi-country Asian cohort. We included children and adolescents who were ART-naïve and <18 years of age at ART initiation from 2011 to 2020 at 17 HIV clinics in six countries. Incidence rates of opportunistic infections (OIs) in the first two years of triple-drug ART (≥3 antiretrovirals) was also reported. Competing risk regression analysis was performed to identify factors associated with first occurrence of OI. In 2,027 children and adolescents (54% males), median age at ART initiation increased from 4.5 years in 2011-2013 to 6.7 in 2017-2020, median CD4 count doubled from 237 cells/μl to 466 cells/μl, and proportion of children who initiated ART as severely immunodeficient decreased from 70% to 45%. During follow-up, 275 (14%) children who received triple-drug ART as first treatment and had at least one clinic visit, developed at least one OI in the first two years of treatment (9.40 per 100 person-years). The incidence rate of any first OI declined from 12.52 to 7.58 per 100 person-years during 2011-2013 and 2017-2020. Lower hazard of OIs were found in those with age at first ART 2-14 years, current CD4 ≥200 cells/μl, and receiving ART between 2017 and 2020. The analysis demonstrated increasing number of children and adolescents starting ART with high CD4 count at ART start. The rate of first OI markedly decreased in children who started ART in more recent years. There remains a clear need for improvement in HIV control strategies in children, by promoting earlier diagnosis and timely treatment., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AHS receives grants to her institution from ViiV Healthcare. All other authors report no potential conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Sornillo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Major intracerebral hemorrhage (ICH) trials have largely been unable to demonstrate therapeutic benefit in improving functional outcomes. This may be partly due to the heterogeneity of ICH outcomes based on their location, where a small strategic ICH could be debilitating, thus confounding therapeutic effects. We aimed to determine the ideal hematoma volume cutoff for different ICH locations in predicting ICH outcomes., Methods: We retrospectively analyzed consecutive ICH patients enrolled in the University of Hong Kong prospective stroke registry from January 2011 to December 2018. Patients with premorbid modified Rankin Scale score >2 or who underwent neurosurgical intervention were excluded. ICH volume cutoff, sensitivity, and specificity in predicting respective 6-month neurological outcomes (good [modified Rankin Scale score 0-2], poor [modified Rankin Scale score 4-6], and mortality) for specific ICH locations were determined using receiver operating characteristic curves. Separate multivariate logistic regression models were also conducted for each location-specific volume cutoff to determine whether these cutoffs were independently associated with respective outcomes., Results: Among 533 ICHs, the volume cutoff for good outcome according to ICH location was 40.5 mL for lobar, 32.5 mL for putamen/external capsule, 5.5 mL for internal capsule/globus pallidus, 6.5 mL for thalamus, 17 mL for cerebellum, and 3 mL for brainstem. ICH smaller than the cutoff for all supratentorial sites had higher odds of good outcomes (all P <0.05). Volumes exceeding 48 mL for lobar, 41 mL for putamen/external capsule, 6 mL for internal capsule/globus pallidus, 9.5 mL for thalamus, 22 mL for cerebellum, and 7.5 mL for brainstem were at greater risk of poor outcomes (all P <0.05). Mortality risks were significantly higher for volumes that exceeded 89.5 mL for lobar, 42 mL for putamen/external capsule, and 21 mL for internal capsule/globus pallidus (all P <0.001). All receiver operating characteristic models for location-specific cutoffs had good discriminant values (area under the curve >0.8), except in predicting good outcome for cerebellum., Conclusions: ICH outcomes differed with location-specific hematoma size. Location-specific volume cutoff should be considered in patient selection for ICH trials., Competing Interests: Disclosures Dr Teo is supported by the Hong Kong Neurological Society Scholarship for Young Neurologist. Dr Lau is supported by the Innovation and Technology Bureau, Research Grants Council, The Government of the Hong Kong SAR, Amgen, Boehringer Ingelheim, Eisai and Pfizer; and has consulted for Amgen, Boehringer Ingelheim, Daiichi Sankyo and Sanofi; all of whom are unrelated to the current work.

Background: The Asia Pacific Society of Infection Control launched the APSIC guide for prevention of catheter associated urinary tract infections in July 2022. It aims to highlight practical recommendations in a concise format designed to assist healthcare facilities in the Asia Pacific region to achieve high standards in infection prevention and control practices during the management and care of patients with a urinary catheter., Methods: The guidelines were developed by an appointed workgroup comprising experts in the Asia Pacific region, following reviews of previously published guidelines and recommendations relevant to each section., Results: It recommends that healthcare institutions have a catheter associated urinary tract infection prevention program that includes surveillance and the use of the insertion and maintenance bundles. Implementation of the bundles is best done using a quality improvement approach with a multidisciplinary team., Conclusions: Healthcare facilities should aim for excellence in care of patients with urinary catheters. It is recommended that healthcare facilities have a catheter associated urinary tract infection prevention program as part of their Infection Prevention and Control program., (© 2023. The Author(s).)

Background: The effect of playing background music on surgical outcomes has been controversial. This prospective case-control study aims to evaluate the impact of music tempo in general surgical settings., Study Design: Six hundred consecutive patients with nonmetastatic breast cancer receiving breast cancer surgery have been recruited since April 2017. Patients were then assigned to 3 arms in consecutive order. The surgeon operated without music in study arm A; the surgeon operated with slow music in study arm B; and in study arm C, the surgeon operated with fast background music. Patients' clinical records were reviewed by an independent blinded assessor., Results: Baseline demographic data were comparable among the 3 study arms. Seven (3.5%) patients from study arm A developed minor complications (Clavien-Dindo class I and II); none developed major complications (Clavien-Dindo class III or above). Six (3.0%) patients from study arm B and C, respectively (slow/fast music groups), developed minor complications; none developed a major complication. Mean blood loss was also similar among the 3 study arms (5.1, 5.1, and 5.2 mL, respectively; p > 0.05). Operating time was significantly shorter in study arm C: 115 minutes (90-145), compared with 125 minutes (100-160) in study arm A (p < 0.0001) and 120 minutes (95-155) in study arm B (p = 0.0024). After a median follow-up of 40 months (3-56), 40 months (3-56), and 39.5 months (3-56), the local recurrence rates were 1.5%, 1%, and 1%, respectively (p > 0.05)., Conclusion: Playing music in the operating room is safe in general surgical settings in experienced hands., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: The case fatality rate and the risk of complications due to pertussis is very high in infants. Asia has the second highest childhood pertussis burden. The study aimed to assess the prevalence, clinical complications, and mortality rates of pertussis disease requiring hospitalization among young infants in Malaysia., Methods: The study was a one-year, hospital-based, multi-site surveillance of infants less than six months of age with symptoms consistent with pertussis and a cross-sectional analysis of their mothers for recent pertussis infection. Information was obtained from medical records and interviews with the parents. Pertussis diagnosis was confirmed for all infants through serum anti-PT titration test or PCR test., Results: 441 possible cases of pertussis were included in this study. Of these, 12.7 % had laboratory confirmation of pertussis. Infants with confirmed pertussis had significantly higher rates of cyanosis (37.5 % vs 8.6 %; p < 0.0001) and apnea (12.5 % vs 3.9 %; p = 0.027) than test-negative infants. Most infants from both groups were in recovery/recovered at discharge. Those with confirmed pertussis had higher case fatality rate than test-negative cases (5.4 % vs 1.0 %; p = 0.094), but the difference did not reach significance. The majority of confirmed pertussis cases (89.3 %) occurred in infants too young to be fully vaccinated or under-vaccinated for their age. Both test-negative and confirmed pertussis resulted in work-day losses and incurred costs for both parents., Conclusions: A high pertussis disease burden persists in infants less than six months of age, especially among those un- and under-vaccinated. Maternal and complete, on-time infant vaccination is important to reduce disease burden., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hishamshah Mohd Ibrahim reports financial support and article publishing charges were provided by Sanofi Pasteur. Denis Macina reports a relationship with Sanofi that includes: employment and equity or stocks., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

To address inborn errors of immunity (IEI) which were underdiagnosed in resource-limited regions, our centre developed and offered free genetic testing for the most common IEI by Sanger sequencing (SS) since 2001. With the establishment of The Asian Primary Immunodeficiency (APID) Network in 2009, the awareness and definitive diagnosis of IEI were further improved with collaboration among centres caring for IEI patients from East and Southeast Asia. We also started to use whole exome sequencing (WES) for undiagnosed cases and further extended our collaboration with centres from South Asia and Africa. With the increased use of Next Generation Sequencing (NGS), we have shifted our diagnostic practice from SS to WES. However, SS was still one of the key diagnostic tools for IEI for the past two decades. Our centre has performed 2,024 IEI SS genetic tests, with in-house protocol designed specifically for 84 genes, in 1,376 patients with 744 identified to have disease-causing mutations (54.1%). The high diagnostic rate after just one round of targeted gene SS for each of the 5 common IEI (X-linked agammaglobulinemia (XLA) 77.4%, Wiskott-Aldrich syndrome (WAS) 69.2%, X-linked chronic granulomatous disease (XCGD) 59.5%, X-linked severe combined immunodeficiency (XSCID) 51.1%, and X-linked hyper-IgM syndrome (HIGM1) 58.1%) demonstrated targeted gene SS should remain the first-tier genetic test for the 5 common X-linked IEI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chan, Wong, Leung, Yang, Fok, Mak, Yao, Ma, Mao, Zhao, Liang, Singh, Barbouche, He, Jiang, Liew, Le, Muktiarti, Santos-Ocampo, Djidjik, Belaid, Ismail, Abdul Latiff, Lee, Chen, Liu, Jin, Wang, Chien, Yu, Raj, Raj, Vaughan, Urban, Berg, Eley, Lee, Isa, Ang, Lee, Yeoh, Shek, Quynh Le, Nguyen, Phan Nguyen Lien, Capulong, Mallillin, Villanueva, Camonayan, Vera, Casis-Hao, Lobo, Foronda, Binas, Boushaki, Kechout, Phongsamart, Wongwaree, Jiratchaya, Lao-Araya, Trakultivakorn, Suratannon, Jirapongsananuruk, Chantveerawong, Kamchaisatian, Chan, Koh, Wong, Fong, Thong, Latiff, Noh, Silva, Jouhadi, Al-Saad, Vignesh, Jindal, Rawat, Gupta, Suri, Yang, Au, Kwok, Chan, Hui, Chua, Duque, Cheong, Chong, Ho, Lee, Wong, Yang, Lee, Tu, Yang and Lau.)

Background: High-level evidence is limited for antibiotic duration in children hospitalized with community-acquired pneumonia (CAP) from First Nations and other at-risk populations of chronic respiratory disorders. As part of a larger study, we determined whether an extended antibiotic course is superior to a standard course for achieving clinical cure at 4 weeks in children 3 months to ≤5 years old hospitalized with CAP., Methods: In our multinational (Australia, New Zealand, Malaysia), double-blind, superiority randomized controlled trial, children hospitalized with uncomplicated, radiographic-confirmed, CAP received 1-3 days of intravenous antibiotics followed by 3 days of oral amoxicillin-clavulanate (80 mg/kg, amoxicillin component, divided twice daily) and then randomized to extended (13-14 days duration) or standard (5-6 days) antibiotics. The primary outcome was clinical cure (complete resolution of respiratory symptoms/signs) 4 weeks postenrollment. Secondary outcomes included adverse events, nasopharyngeal bacterial pathogens and antimicrobial resistance at 4 weeks., Results: Of 372 children enrolled, 324 fulfilled the inclusion criteria and were randomized. Using intention-to-treat analysis, between-group clinical cure rates were similar (extended course: n = 127/163, 77.9%; standard course: n = 131/161, 81.3%; relative risk = 0.96, 95% confidence interval = 0.86-1.07). There were no significant between-group differences for adverse events (extended course: n = 43/163, 26.4%; standard course, n = 32/161, 19.9%) or nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus or antimicrobial resistance., Conclusions: Among children hospitalized with pneumonia and at-risk of chronic respiratory illnesses, an extended antibiotic course was not superior to a standard course at achieving clinical cure at 4 weeks. Additional research will identify if an extended course provides longer-term benefits., Competing Interests: A.B.C. is supported by a National Health and Medical Research Council practitioner fellowship (number 1154302) and Children’s Hospital Foundation Queensland (Grant 50286). The other authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Preventing and/or reducing acute lower respiratory infections (ALRIs) in young children will lead to substantial short and long-term clinical benefits. While immunisation with pneumococcal conjugate vaccines (PCV) reduces paediatric ALRIs, its efficacy for reducing infant ALRIs following maternal immunisation has not been studied. Compared to other PCVs, the 10-valent pneumococcal- Haemophilus influenzae Protein D conjugate vaccine (PHiD-CV) is unique as it includes target antigens from two common lower airway pathogens, pneumococcal capsular polysaccharides and protein D, which is a conserved H. influenzae outer membrane lipoprotein. Aims: The primary aim of this randomised controlled trial (RCT) is to determine whether vaccinating pregnant women with PHiD-CV (compared to controls) reduces ALRIs in their infants' first year of life. Our secondary aims are to evaluate the impact of maternal PHiD-CV vaccination on different ALRI definitions and, in a subgroup, the infants' nasopharyngeal carriage of pneumococci and H. influenzae , and their immune responses to pneumococcal vaccine type serotypes and protein D. Methods: We are undertaking a parallel, multicentre, superiority RCT (1:1 allocation) at four sites across two countries (Australia, Malaysia). Healthy pregnant Australian First Nation or Malaysian women aged 17-40 years with singleton pregnancies between 27 +6 and 34 +6 weeks gestation are randomly assigned to receive either a single dose of PHiD-CV or usual care. Treatment allocation is concealed. Study outcome assessors are blinded to treatment arms. Our primary outcome is the rate of medically attended ALRIs by 12-months of age. Blood and nasopharyngeal swabs are collected from infants at birth, and at ages 6- and 12-months (in a subset). Our planned sample size ( n = 292) provides 88% power (includes 10% anticipated loss to follow-up). Discussion: Results from this RCT potentially leads to prevention of early and recurrent ALRIs and thus preservation of lung health during the infant's vulnerable period when lung growth is maximum. The multicentre nature of our study increases the generalisability of its future findings and is complemented by assessing the microbiological and immunological outcomes in a subset of infants. Clinical Trial Registration: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374381, identifier: ACTRN12618000150246., Competing Interests: KG participated in a rotavirus strain outbreak advisory board for GlaxoSmithKline, Rixensart, Belgium. ABC has received fees to the institution from work relating to IDMC membership of an unlicensed vaccine (GSK), and a COVID-19 vaccine (Moderna) outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chang, Toombs, Chatfield, Mitchell, Fong, Binks, Smith-Vaughan, Pizzutto, Lust, Morris, Marchant, Yerkovich, O'Farrell, Torzillo, Maclennan, Simon, Unger, Ellepola, Odendahl, Marshall, Swamy and Grimwood.)

Primary immunodeficiency diseases refer to inborn errors of immunity (IEI) that affect the normal development and function of the immune system. The phenotypical and genetic heterogeneity of IEI have made their diagnosis challenging. Hence, whole-exome sequencing (WES) was employed in this pilot study to identify the genetic etiology of 30 pediatric patients clinically diagnosed with IEI. The potential causative variants identified by WES were validated using Sanger sequencing. Genetic diagnosis was attained in 46.7% (14 of 30) of the patients and categorized into autoinflammatory disorders (n = 3), diseases of immune dysregulation (n = 3), defects in intrinsic and innate immunity (n = 3), predominantly antibody deficiencies (n = 2), combined immunodeficiencies with associated and syndromic features (n = 2) and immunodeficiencies affecting cellular and humoral immunity (n = 1). Of the 15 genetic variants identified, two were novel variants. Genetic findings differed from the provisional clinical diagnoses in seven cases (50.0%). This study showed that WES enhances the capacity to diagnose IEI, allowing more patients to receive appropriate therapy and disease management., (© 2021 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.)

Objective: To implement a standardized cause of death reporting and review process to systematically disaggregate causes of HIV-related deaths in a cohort of Asian children and adolescents., Design: Death-related data were retrospectively and prospectively assessed in a longitudinal regional cohort study., Methods: Children under routine HIV care at sites in Cambodia, India, Indonesia, Malaysia, Thailand, and Vietnam between 2008 and 2017 were followed. Causes of death were reported and then independently and centrally reviewed. Predictors were compared using competing risks survival regression analyses., Results: Among 5918 children, 5523 (93%; 52% male) had ever been on combination antiretroviral therapy. Of 371 (6.3%) deaths, 312 (84%) occurred in those with a history of combination antiretroviral therapy (crude all-cause mortality 9.6 per 1000 person-years; total follow-up time 32 361 person-years). In this group, median age at death was 7.0 (2.9-13) years; median CD4 cell count was 73 (16-325) cells/μl. The most common underlying causes of death were pneumonia due to unspecified pathogens (17%), tuberculosis (16%), sepsis (8.0%), and AIDS (6.7%); 12% of causes were unknown. These clinical diagnoses were further grouped into AIDS-related infections (22%) and noninfections (5.8%), and non-AIDS-related infections (47%) and noninfections (11%); with 12% unknown, 2.2% not reviewed. Higher CD4 cell count and better weight-for-age z-score were protective against death., Conclusion: Our standardized cause of death assessment provides robust data to inform regional resource allocation for pediatric diagnostic evaluations and prioritization of clinical interventions, and highlight the continued importance of opportunistic and nonopportunistic infections as causes of death in our cohort.

Background: This study aimed to examine the influence of kinesiology taping (KT), various overhead stroke techniques, and their interactions on shoulder girdle muscle activity and on sports performance in badminton players with shoulder impingement syndrome., Methods: Twenty-five amateur badminton players with shoulder impingement syndrome participated in the study. Each was exposed to two KT conditions (no taping and taping) while performing four badminton strokes (defensive clear, attacking clear, smash, and drop shot) in a random order. Surface electromyography (EMG) was used to evaluate the activity of the pectoralis major, anterior deltoid, infraspinatus, and latissimus dorsi muscles. The EMG data are expressed as a percentage of the EMG amplitude recorded during a maximal voluntary isometric contraction of the respective muscles. The shuttlecock speed was also measured via video analysis., Results: The pectoralis major, anterior deltoid, infraspinatus, and latissimus dorsi EMG amplitudes were greatest during smashes (P<0.05), followed in general by attacking clearances (P<0.05) and defensive clearances (P<0.05). Drop shots induced the lowest EMG amplitudes in the shoulder girdle muscles (P<0.05). No significant main effect of the KT condition or KT-badminton stroke interaction effects were found (P>0.05)., Conclusions: The use of KT conferred no immediate benefits in improving shoulder girdle muscle activity or sports performance in amateur badminton players with shoulder impingement syndrome. Shoulder girdle muscle activity and sports performance were primarily influenced by the badminton overhead stroke techniques.

Introduction: Early childhood pneumonia is a common problem globally with long-term complications that include bronchiectasis and chronic obstructive pulmonary disease. It is biologically plausible that these long-term effects may be minimised in young children at increased risk of such sequelae if any residual lower airway infection and inflammation in their developing lungs can be treated successfully by longer antibiotic courses. In contrast, shortened antibiotic treatments are being promoted because of concerns over inducing antimicrobial resistance. Nevertheless, the optimal treatment duration remains unknown. Outcomes from randomised controlled trials (RCTs) on paediatric pneumonia have focused on short-term (usually <2 weeks) results. Indeed, no long-term RCT-generated outcome data are available currently. We hypothesise that a longer antibiotic course, compared with the standard treatment course, reduces the risk of chronic respiratory symptoms/signs or bronchiectasis 24 months after the original pneumonia episode., Methods and Analysis: This multicentre, parallel, double-blind, placebo-controlled randomised trial involving seven hospitals in six cities from three different countries commenced in May 2016. Three-hundred-and-fourteen eligible Australian Indigenous, New Zealand Māori/Pacific and Malaysian children (aged 0.25 to 5 years) hospitalised for community-acquired, chest X-ray (CXR)-proven pneumonia are being recruited. Following intravenous antibiotics and 3 days of amoxicillin-clavulanate, they are randomised (stratified by site and age group, allocation-concealed) to receive either: (i) amoxicillin-clavulanate (80 mg/kg/day (maximum 980 mg of amoxicillin) in two-divided doses or (ii) placebo (equal volume and dosing frequency) for 8 days. Clinical data, nasopharyngeal swab, bloods and CXR are collected. The primary outcome is the proportion of children without chronic respiratory symptom/signs of bronchiectasis at 24 months. The main secondary outcomes are 'clinical cure' at 4 weeks, time-to-next respiratory-related hospitalisation and antibiotic resistance of nasopharyngeal respiratory bacteria., Ethics and Dissemination: The Human Research Ethics Committees of all the recruiting institutions (Darwin: Northern Territory Department of Health and Menzies School of Health Research; Auckland: Starship Children's and KidsFirst Hospitals; East Malaysia: Likas Hospital and Sarawak General Hospital; Kuala Lumpur: University of Malaya Research Ethics Committee; and Klang: Malaysian Department of Health) have approved the research protocol version 7 (13 August 2018). The RCT and other results will be submitted for publication., Trial Registration: ACTRN12616000046404., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Disclosure of HIV status to HIV-infected children and adolescents is a major care challenge. We describe current site characteristics related to disclosure of HIV status in resource-limited paediatric HIV care settings within the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium., Methods: An online site assessment survey was conducted across the paediatric HIV care sites within six global regions of IeDEA. A standardized questionnaire was administered to the sites through the REDCap platform., Results: From June 2014 to March 2015, all 180 sites of the IeDEA consortium in 31 countries completed the online survey: 57% were urban, 43% were health centres and 86% were integrated clinics (serving both adults and children). Almost all the sites (98%) reported offering disclosure counselling services. Disclosure counselling was most often provided by counsellors (87% of sites), but also by nurses (77%), physicians (74%), social workers (68%), or other clinicians (65%). It was offered to both caregivers and children in 92% of 177 sites with disclosure counselling. Disclosure resources and procedures varied across geographical regions. Most sites in each region reported performing staff members' training on disclosure (72% to 96% of sites per region), routinely collecting HIV disclosure status (50% to 91%) and involving caregivers in the disclosure process (71% to 100%). A disclosure protocol was available in 14% to 71% of sites. Among the 143 sites (79%) routinely collecting disclosure status process, the main collection method was by asking the caregiver or child (85%) about the child's knowledge of his/her HIV status. Frequency of disclosure status assessment was every three months in 63% of the sites, and 71% stored disclosure status data electronically., Conclusion: The majority of the sites reported offering disclosure counselling services, but educational and social support resources and capacities for data collection varied across regions. Paediatric HIV care sites worldwide still need specific staff members' training on disclosure, development and implementation of guidelines for HIV disclosure, and standardized data collection on this key issue to ensure the long-term health and wellbeing of HIV-infected youth., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.)

Background.: Regular CD4 count testing is often used to monitor antiretroviral therapy efficacy. However, this practice may be redundant in children with a suppressed human immunodeficiency virus (HIV) viral load., Methods: Study end points were as follows: (1) a CD4 count <200 cells/mm3 followed by a CD4 count ≥200 cells/mm3 (transient CD4 <200); (2) CD4 count <200 cells/mm3 confirmed within 6 months (confirmed CD4 <200); and (3) a new or recurrent World Health Organization (WHO) stage 3 or 4 illness (clinical failure). Kaplan-Meier curves and Cox regression were used to evaluate rates and predictors of transient CD4 <200, confirmed CD4 <200, and clinical failure among virally suppressed children aged 5-15 years who were enrolled in the TREAT Asia Pediatric HIV Observational Database., Results: Data from 967 children were included in the analysis. At the time of confirmed viral suppression, median age was 10.2 years, 50.4% of children were female, and 95.4% were perinatally infected with HIV. Median CD4 cell count was 837 cells/mm3, and 54.8% of children were classified as having WHO stage 3 or 4 disease. In total, 18 transient CD4 <200 events, 2 confirmed CD4 <200 events, and10 clinical failures occurred at rates of 0.73 (95% confidence interval [95% CI], 0.46-1.16), 0.08 (95% CI, 0.02-0.32), and 0.40 (95% CI, 0.22-0.75) events per 100 patient-years, respectively. CD4 <500 cells/mm3 at the time of viral suppression confirmation was associated with higher rates of both CD4 outcomes., Conclusions: Regular CD4 testing may be unnecessary for virally suppressed children aged 5-15 years with CD4 ≥500 cells/mm3., (© The Author 2016. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Injuries and illnesses for professional tennis athletes disrupt training, competition, and progression in the sport and represent a major reason for athlete withdrawal or retirement from a tournament. Few descriptive epidemiological studies have focused on these trends in elite tennis athletes., Purpose: To examine the causes of professional tennis player withdrawal or retirement from United States Tennis Association (USTA) Pro Circuit tournaments during 2013., Study Design: Descriptive epidemiology study., Level of Evidence: Level 4., Methods: Tournament records from the 2013 USTA Pro Circuit season were retrospectively reviewed for incidences of injury and illness that resulted in athlete withdrawal from the tournament. Data were reported as incidence rates per 1000 match exposures and rate ratios., Results: There were 70 medical conditions over the course of 27 competitions (20,988 match exposures), for an overall incidence rate of 3.34 per 1000 match exposures. Women were more likely to injure themselves on clay courts compared with hard courts (rate ratio, 4.67; 95% confidence interval [CI], 1.41-19.85) and in the first half of the season compared with the second half (rate ratio, 3.95; 95% CI, 1.13-21.17). Men had a higher injury rate than women (rate ratio, 1.88; 95% CI, 1.17-3.63), and muscle-/tendon-related injuries were 6 times more likely than all other injuries (95% CI, 2.81-14.69)., Conclusion: Women were more likely to experience an injury when playing on clay court surfaces, and they also experienced more injuries during the first half of the season. Injury rates for men often peaked during the months that players could qualify for Grand Slam competitions. There was a predominance of injuries in men compared with women.

Importance: Human papillomavirus (HPV) infections cause anogenital cancers and warts. The 9-valent HPV vaccine provides protection against 7 high-risk types of HPV responsible for 90% of cervical cancers and 2 other HPV types accounting for 90% of genital warts., Objective: To determine whether HPV type-specific antibody responses would be noninferior among girls and boys aged 9 to 14 years after receiving 2 doses of the 9-valent HPV vaccine compared with adolescent girls and young women aged 16 to 26 years receiving 3 doses., Design, Setting, and Participants: Open-label, noninferiority, immunogenicity trial conducted at 52 ambulatory care sites in 15 countries. The study was initiated on December 16, 2013, with the last participant visit for this report on June 19, 2015. Five cohorts were enrolled: (1) girls aged 9 to 14 years to receive 2 doses 6 months apart (n = 301); (2) boys aged 9 to 14 years to receive 2 doses 6 months apart (n = 301); (3) girls and boys aged 9 to 14 years to receive 2 doses 12 months apart (n = 301); (4) girls aged 9 to 14 years to receive 3 doses over 6 months (n = 301); and (5) a control group of adolescent girls and young women aged 16 to 26 years to receive 3 doses over 6 months (n = 314)., Interventions: Two doses of the 9-valent HPV vaccine administered 6 or 12 months apart or 3 doses administered over 6 months., Main Outcomes and Measures: The primary end point was prespecified as the antibody response against each HPV type assessed 1 month after the last dose using a competitive immunoassay. Each of the three 2-dose regimens was compared with the standard 3-dose schedule in adolescent girls and young women using a noninferiority margin of 0.67 for the ratio of the antibody geometric mean titers., Results: Of the 1518 participants (753 girls [mean age, 11.4 years]; 451 boys [mean age, 11.5 years]; and 314 adolescent girls and young women [mean age, 21.0 years]), 1474 completed the study and data from 1377 were analyzed. At 4 weeks after the last dose, HPV antibody responses in girls and boys given 2 doses were noninferior to HPV antibody responses in adolescent girls and young women given 3 doses (P < .001 for each HPV type). Compared with adolescent girls and young women who received 3 doses over 6 months, the 1-sided 97.5% CIs for the ratio of HPV antibody geometric mean titers at 1 month after the last dose across the 9 HPV subtypes ranged from 1.36 to ∞ to 2.50 to ∞ for girls who received 2 doses 6 months apart; from 1.37 to ∞ to 2.55 to ∞ for boys who received 2 doses 6 months apart; and from 1.61 to ∞ to 5.36 to ∞ for girls and boys who received 2 doses 12 months apart., Conclusions and Relevance: Among girls and boys aged 9 to 14 years receiving 2-dose regimens of a 9-valent HPV vaccine separated by 6 or 12 months, immunogenicity 4 weeks after the last dose was noninferior to a 3-dose regimen in a cohort of adolescent girls and young women. Further research is needed to assess persistence of antibody responses and effects on clinical outcomes., Trial Registration: clinicaltrials.gov Identifier: NCT01984697.

Background: Information on antiretroviral therapy (ART) use in HIV-infected children with severe malnutrition (SM) is lacking. We investigated long-term ART outcomes in this population., Methods: Children enrolled in the TREAT Asia Pediatric HIV Observational Database who had SM (weight-for-height or body mass index-for-age Z score less than -3) at ART initiation were analyzed. Generalized estimating equations were used to investigate poor weight recovery (weight-for-age Z score less than -3) and poor CD4% recovery (CD4% <25), and competing risk regression was used to analyze mortality and toxicity-associated treatment modification., Results: Three hundred fifty-five (11.9%) of 2993 children starting ART had SM. Their median weight-for-age Z score increased from -5.6 at ART initiation to -2.3 after 36 months. Not using trimethoprim-sulfamethoxazole prophylaxis at baseline was associated with poor weight recovery [odds ratio: 2.49 vs. using; 95% confidence interval (CI): 1.66-3.74; P < 0.001]. Median CD4% increased from 3.0 at ART initiation to 27.2 after 36 months, and 56 (15.3%) children died during follow-up. More profound SM was associated with poor CD4% recovery (odds ratio: 1.78 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.08-2.92; P = 0.023) and mortality (hazard ratio: 2.57 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.24-5.33; P = 0.011). Twenty-two toxicity-associated ART modifications occurred at a rate of 2.4 per 100 patient-years, and rates did not differ by malnutrition severity., Conclusion: Trimethoprim-sulfamethoxazole prophylaxis is important for the recovery of weight-for-age in severely malnourished children starting ART. The extent of SM does not impede weight-for-age recovery or antiretroviral tolerability, but CD4% response is compromised in children with a very low weight-for-height/body mass index-for-age Z score, which may contribute to their high rate of mortality.

Purpose: About a third of untreated, perinatally HIV-infected children reach adolescence. We evaluated the durability and effectiveness of non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) in this population., Methods: Data from perinatally HIV-infected, antiretroviral-naïve patients initiated on NNRTI-based ART aged 10-19 years who had ≥6 months of follow-up were analyzed. Competing risk regression was used to assess predictors of NNRTI substitution and clinical failure (World Health Organization Stage 3/4 event or death). Viral suppression was defined as a viral load <400 copies/mL., Results: Data from 534 adolescents met our inclusion criteria (56.2% female; median age at treatment initiation 11.8 years). After 5 years of treatment, median height-for-age z score increased from -2.3 to -1.6, and median CD4+ cell count increased from 131 to 580 cells/mm(3). The proportion of patients with viral suppression after 6 months was 87.6% and remained >80% up to 5 years of follow-up. NNRTI substitution and clinical failure occurred at rates of 4.9 and 1.4 events per 100 patient-years, respectively. Not using cotrimoxazole prophylaxis at ART initiation was associated with NNRTI substitution (hazard ratio [HR], 1.5 vs. using; 95% confidence interval [CI] = 1.0-2.2; p = .05). Baseline CD4+ count ≤200 cells/mm(3) (HR, 3.3 vs. >200; 95% CI = 1.2-8.9; p = .02) and not using cotrimoxazole prophylaxis at ART initiation (HR, 2.1 vs. using; 95% CI = 1.0-4.6; p = .05) were both associated with clinical failure., Conclusions: Despite late ART initiation, adolescents achieved good rates of catch-up growth, CD4+ count recovery, and virological suppression. Earlier ART initiation and routine cotrimoxazole prophylaxis in this population may help to reduce current rates of NNRTI substitution and clinical failure., (Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Melioidosis is an important cause of community-acquired infection in Southeast Asia and northern Australia. Studies from endemic countries have demonstrated differences in the epidemiology and clinical features among children diagnosed with melioidosis. This suggests that local data are needed to determine the risk factors and outcome in specific areas., Methods: This was a retrospective study of all children admitted to Likas Women's and Children Hospital, Kota Kinabalu, Sabah, Malaysia, with a blood or clinical sample positive for Burkholderia pseudomallei from 2001 to 2012., Results: Of 28 children with confirmed melioidosis, 27 records were reviewed including 11 (41%) children with thalassemia major. Twenty of the children had bacteremia, and 16 (59%) had a fatal outcome. Six children had chronic disease, and none died. Empiric use of antibiotics not specific for B. pseudomallei was associated with increased risk of death (P < .001). The annual incidence of melioidosis in children with thalassemia major from 2001 to 2010 was 140 per 100 000/year vs 0.33 per 100 000/year for other children (P < .001). After institution of iron chelation therapy in 2010, no child with thalassemia major was diagnosed with melioidosis in 2011 or 2012., Conclusions: Pediatric melioidosis in Sabah is associated with a high proportion of bacteremia and death. Thalassemia major was a major risk factor for melioidosis among children from 2001 to 2010, but infections decreased markedly from 2011 to 2012 after universal availability of iron chelation therapy. Inappropriate empiric therapy was associated with an increased risk of death., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: We determined the prevalence and incidence of liver dysfunction before and after initiation of combination antiretroviral therapy (cART) in the TREAT Asia Pediatric HIV Observational Database., Methods: Data from children initiated on cART between 2 and 18 years of age with baseline alanine aminotransferase (ALT) available before and at least once after cART initiation in TREAT Asia Pediatric HIV Observational Database between 2008 and 2012 were analyzed. Prevalence and incidence of liver dysfunction and biomarkers including the aspartate aminotransferase to platelet ratio index and FIB4 index (a noninvasive panel to stage liver disease) were assessed., Results: Data from 1930 children were included. Their median age was 6.9 years; 49% were male; 98% were perinatally infected and 94% were initiated on non-nucleoside reverse transcriptase-based cART regimens. Before cART, the prevalence of ALT ≥3 times the upper limit of normal (×ULN) was 5.8%. There were 8.5% of children with aspartate aminotransferase to platelet ratio index >1.5 (suggestive of liver fibrosis) and 2.7% with FIB4 index >1.3 (predictive of possible cirrhosis). Among the 1143 cases with normal baseline ALT (≤1×ULN), the incidence of ALT 3×ULN after cART was 1.19 of 1000 person-months (95% confidence interval: 0.93-1.51). Two of 350 with available tests (0.6%) met Hy's law (ALT >3×ULN and total bilirubin >2×ULN). By multivariate analysis, baseline hemoglobin <7.5 g/dL was a predictor of ALT >3×ULN, whereas age 5-9 years at cART initiation was protective for liver dysfunction., Conclusions: We demonstrated a low prevalence and incidence of liver dysfunction before and after cART initiation in children with normal baseline chemistries. In this population facing life-long cART, prospective surveillance for emergence of liver disease is warranted.

Background: More perinatally HIV-infected children in Asia are reaching adolescence., Methods: We analyzed data from July 1991 to March 2011 reported by 18 clinics in 6 countries of children age >12 years., Results: Of 1254 adolescents, 33 (2.6%) died, and 52 (4.1%) were lost to follow-up within 2.4-year (3566 person-years) median follow-up period. Of 1061 adolescents under active follow-up, 485 (46%) were male, median (interquartile range) age was 14.7 (13.3-16.4) years, 73% had lost a parent(s), 93% attended school and 62% were aware of their HIV status. At the most recent evaluation, 93% were receiving highly active antiretroviral therapy, 71% (N = 737/1035) had CD4 ≥ 500 cells/mm(3) and 87% (N = 718/830) had viral load (VL) <400 copies/mL. Current CD4 ≥ 200 cells/mm(3), no previous World Health Organization stage 3 or 4 and being on a first-line regimen were independently associated with recent VL <400 copies/mL. Current age <15 years, VL <400 copies/mL, CD4 15-24% (vs. <10%) at antiretroviral therapy initiation, no previous World Health Organization stage 3 or 4 and antiretroviral therapy duration of ≥ 1 year were associated with recent CD4 ≥ 500 cells/mm(3). Primary causes of death after age 12 were opportunistic infections (N = 15/33) and other AIDS- or treatment-related conditions (N = 9/33). Those at age 12 with CD4 <200 versus ≥ 500 cells/mm and those with VL ≥ 10,000 versus <10,000 copies/mL were 17.4 and 4.76 times more likely to die in adolescence, respectively., Conclusion: Adolescents in this cohort have been successfully maintained in HIV care. Initiating treatment at earlier stages of disease was associated with immune recovery and virologic suppression during adolescence.

A multicenter, retrospective, observational study was conducted to determine prevalence, characteristics, management, and outcome of pulmonary tuberculosis (PTB) in Asian HIV-infected children in the TREAT Asia Pediatric HIV Observational Database (TApHOD). Data on PTB episodes diagnosed during the period between 12 months before antiretroviral therapy (ART) initiation and December 31, 2009 were extracted. A total of 2678 HIV-infected children were included in TApHOD over a 13-year period; 457 developed PTB, giving a period prevalence of 17.1% (range 5.7-33.0% per country). There were a total of 484 PTB episodes; 27 children had 2 episodes each. There were 21 deaths (4.3%). One third of episodes (n=175/484) occurred after ART initiation at a median of 14.1 months (interquartile range [IQR] 2.5-28.8 months). The median (IQR) CD4+ values were 9.0% (3.0-16.0%) and 183.5 (37.8-525.0) cells/mm(3) when PTB was diagnosed. Most episodes (n=424/436, 97.3%) had abnormal radiographic findings compatible with PTB, whereas half (n=267/484, 55.2%) presented with clinical characteristics of PTB. One third of those tested (n=42/122, 34.4%) had bacteriological evidence of PTB. Of the 156 episodes (32.2%) that were accompanied with extrapulmonary TB, pleuritis was the most common manifestation (81.4%). After treatment completion, most episodes (n=396/484, 81.9%) were recorded as having positive outcomes (cured, treatment completed and child well, and improvement). The prevalence of PTB among Asian HIV-infected children in our cohort was high. Children with persistent immunosuppression remain vulnerable to PTB even after ART initiation.

Background: There are limited data on treatment-related anemia in Asian HIV-infected children., Methods: Data from Asian HIV-infected children aged <18 years on first-line highly active antiretroviral therapy (HAART) were used. Children who had pre-existing severe anemia at baseline were excluded. Anemia was graded using the United States Division of AIDS (DAIDS) 2004 table. Potential risk factors for severe anemia were assessed by logistic regression., Results: Data from 1648 children (51.9% female, 62.8% World Health Organization (WHO) stage 3/4) were analyzed. Median (interquartile range) age was 6.8 (3.7-9.6) years, CD4% was 9 (3-16)%, and plasma HIV-RNA was 5.2 (4.7-5.6) log10 copies/ml at HAART initiation in those with available testing. The most common regimens were stavudine/lamivudine/nevirapine (42%) and zidovudine/lamivudine/nevirapine (25%). Severe anemia was identified in 47 (2.9%) children after a median time of 6 months after HAART initiation, with an incidence rate of 5.4 per 100 child-years. Mild anemia or moderate anemia at baseline (p = 0.024 and p = 0.005, respectively), previous or current use of zidovudine (p < 0.0001 and p = 0.013, respectively), and male sex (p = 0.008) were associated with severe anemia. Higher weight-for-age z-score (p = 0.004) was protective., Conclusions: The incidence of severe anemia in Asian HIV-infected children after HAART initiation was low and mainly occurred during the first few months after HAART initiation. Mild to moderate anemia at baseline and using zidovudine were independent risk factors for the development of severe anemia., (Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The World Health Organization (WHO) recommends boosted protease inhibitor (bPI)-based HAART after failing non-nucleoside reverse transcriptase inhibitor (NNRTI) treatment. We examined outcomes of this regimen in Asian HIV-infected children., Methods: Children from five Asian countries in the TREAT Asia Pediatric HIV Observational Database (TApHOD) with ≥ 24 weeks of NNRTI-based HAART followed by ≥ 24 weeks of bPI-based HAART were eligible. Primary outcomes were the proportions with virological suppression (HIV RNA < 400 copies/ml) and immune recovery (CD4+ T-cell percentage [CD4%]≥ 25% if age < 5 years and CD4+ T-cell count ≥ 500 cells/mm3 if age ≥ 5 years) at 48 and 96 weeks., Results: Of 3,422 children, 153 were eligible; 52% were female. At switch, median age was 10 years, 26% were in WHO stage 4. Median weight-for-age z-score (WAZ) was -1.9 (n = 121), CD4% was 12.5% (n = 106), CD4+ T-cell count was 237 cells/mm3 (n = 112), and HIV RNA was 4.6 log10 copies/ml (n = 61). The most common bPI was lopinavir/ritonavir (83%). At 48 weeks, 61% (79/129) had immune recovery, 60% (26/43) had undetectable HIV RNA and 73% (58/79) had fasting triglycerides ≥ 130 mg/dl. By 96 weeks, 70% (57/82) achieved immune recovery, 65% (17/26) had virological suppression, and hypertriglyceridaemia occurred in 66% (33/50). Predictors for virological suppression at week 48 were longer duration of NNRTI-based HAART (P = 0.006), younger age (P = 0.007), higher WAZ (P = 0.020) and HIV RNA at switch < 10,000 copies/ml (P = 0.049)., Conclusions: In this regional cohort of Asian children on bPI-based second-line HAART, 60% of children tested had immune recovery by 1 year, and two-thirds had hyperlipidaemia, highlighting difficulties in optimizing second-line HAART with limited drug options.

Taekwondo (TKD) is a popular sport among adolescents. This study aims to (a) compare the balance performance between adolescent TKD practitioners at different levels of expertise with nonpractitioners and (b) determine the sensory system(s) that contributed to the balance function in adolescents with and without TKD training. Subjects with >5 years of TKD training (n = 11), <4 years of training (n = 10), and no training (n = 10) participated in this study. The sway velocity, somatosensory, vestibular and visual ratios were recorded during standing on a balance testing system. Both short- and long-term TKD practitioners swayed slower than control subjects when standing on one leg (p = .016 and 0.012, respectively). However, only short-term practitioners have better visual ratio (p = .018) and vestibular ratio (p = .029) than control subjects. There was no significant difference in the somatosensory ratio among the 3 groups. We conclude that adolescents undertaking TKD training may have better balance performance than untrained subjects.

Introduction: We report responses to combination antiretroviral therapy (cART) in the Therapeutics Research, Education, and AIDS Training in Asia Pediatric HIV Observational Database., Methods: Children included were those who had received cART (ie, ≥3 antiretrovirals) at <18 years. The analysis was intention-to-treat by the first cART regimen. Median values are provided with interquartile ranges; hazard ratios (HRs) with 95% confidence intervals., Results: Of the 1655 children included, 50.4% were male, with a median age at cART of 7.0 (3.9-9.8) years and CD4 of 8% (2.0%-15%); 92.5% were started on an NNRTI; median duration of follow-up was 2.9 (1.4-4.6) years. Loss-to-follow-up and death rates were 4.2 (3.7-4.8) and 2.1 (1.7-2.5) per 100 person-years, respectively. At 36 months, median CD4 was 26% (21%-31%); 81% of those with viral load (n = 302) were <400 copies per milliliter. Children who reached CD4 ≥25% within 5 years were more likely to be females (HR: 1.4; 1.2-1.7), start before 18 months old (HR: 3.8; 2.4-6.2), lack a history of monotherapy/dual therapy (HR: 1.7; 1.4-2.5), and have a higher baseline CD4 (per 10% increase: HR: 2; 1.9-2.2)., Conclusions: These data underscore the need for early diagnosis and cART initiation to preserve immune function.

Background: Finding and isolating rare tumor cells in blood allows for diagnosis of disseminated cancer and for molecular profiling to direct the choice of biologic therapy. We explored whether the candidate gene therapy virus NV1066-designed to specifically infect cancer cells and express green fluorescence protein (GFP)-can be used for rapid infection, identification, and isolation of rare circulating tumor cells (CTC) in human whole blood., Methods: Mixtures of human cancer cell lines and human whole blood were exposed to NV1066 or heat-inactivated virus, incubated, and then examined for GFP expression by fluorescence microscopy and flow cytometry. Fluorescence-assisted cell sorting (FACS) was used to determine the efficiency of virally assisted tumor cell isolation. Sorted cells were subsequently stained for carcinoembryonic antigen (CEA) to determine if cells isolated in this way would maintain sufficient cellular integrity for molecular characterization., Results: In our study, there was 100% specificity for detection of cancer cells. Detection was consistent even at the highest dilution tested (10 cancer cells in 10 ml whole blood). The processing involved simple incubation without the technical demands of immunohistochemistry. FACS allowed for rapid isolation of GFP-expressing cells. Cells isolated by this method can subsequently undergo molecular characterization., Conclusion: Oncolytic herpes simplex virus mediated green fluorescence in combination with FACS is a novel technique for the identification and isolation of cancer cells in an experimental model of blood-borne metastases. This procedure is a promising method for improving our diagnosis, staging, and molecular profiling of cancer.

Background: Postmortem and in vivo imaging data support the hypothesis that premature myelin breakdown and subsequent homeostatic remyelination attempts with increased oligodendrocyte and iron levels may contribute to Huntington's Disease (HD) pathogenesis and the symmetrical progress of neuronal loss from earlier-myelinating striatum to later-myelinating regions. A unique combination of in vivo tissue integrity and iron level assessments was used to examine the hypothesis., Methods: A method that uses two Magnetic resonance imaging (MRI) instruments operating at different field-strengths was used to quantify the iron content of ferritin molecules (ferritin iron) as well as tissue integrity in eight regions in 11 HD and a matched group of 27 healthy control subjects. Three white matter regions were selected based on their myelination pattern (early to later-myelinating) and fiber composition. These were frontal lobe white matter (Fwm) and splenium and genu of the corpus callosum (Swm and Gwm). In addition, gray matter structures were also chosen based on their myelination pattern and fiber composition. Three striatum structures were assessed [caudate, putamen, and globus pallidus (C, P, and G)] as well as two comparison gray matter regions that myelinate later in development and are relatively spared in HD [Hippocampus (Hipp) and Thalamus (Th)]., Results: Compared to healthy controls, HD ferritin iron levels were significantly increased in striatum C, P, and G, decreased in Fwm and Gwm, and were unchanged in Hipp, Th, and Swm. Loss of tissue integrity was observed in C, P, Fwm, and especially Swm but not Hipp, Th, G, or Gwm. This pattern of findings was largely preserved when a small subset of HD subjects early in the disease process was examined., Conclusions: The data suggest early in the HD process, myelin breakdown and changes in ferritin iron distribution underlie the pattern of regional toxicity observed in HD. Prospective studies are needed to verify myelin breakdown and increased iron levels are causal factors in HD pathogenesis. Tracking the effects of novel interventions that reduce myelin breakdown and iron accumulation in preclinical stages of HD could hasten the development of preventive treatments.

Objectives: To compare the effects of short-term and long-term Tai Chi training on the sensorimotor and balance performance of able-bodied subjects., Design: A nonrandomized cross-sectional controlled trial., Setting: Sport laboratory., Participants: Forty-eight healthy subjects, 16 with 3 months of experience in Tai Chi training, 16 with 1 to 3 years of experience in Tai Chi training, and 16 with no experience in Tai Chi training., Intervention: Experimental., Main Outcome Measures: The reflex contraction latencies (reaction time) of medial hamstrings and gastrocnemius after perturbation, the active knee joint angle-repositioning error, and the balance time on a tilt board were measured and analyzed with 1-way analysis of covariance. Significant results were further analyzed with post hoc linear contrasts., Results: Long-term Tai Chi practitioners had a significantly faster reflex reaction time in hamstrings (P<.000) and gastrocnemius (P=.043) muscles and a longer balance time on a tilt board (P<.000) than short-term Tai Chi practitioners and nonpractitioners. Both long- and short-term Tai Chi practitioners had significantly less knee joint angle-repositioning error than nonpractitioners (P=.001 and P=.027, respectively)., Conclusions: Tai Chi training of more than 1 year might have the benefits of faster hamstrings and gastrocnemius reflex reaction and improved knee joint position sense (JPS). These changes might be associated with an improved dynamic standing balance. Better knee JPS was shown in subjects with 3 months of Tai Chi practice, but this had not led to a significant improvement in balance.

Budd-Chiari syndrome is a rare condition characterized by thrombosis within the hepatic veins and inferior vena cava. A case of Budd-Chiari syndrome is presented in a patient who presented acutely 3 days following laparoscopic cholecystectomy for acalculous cholecystitis. A discussion of pathology and findings on calcium colloid scintigram, CT scan and Doppler ultrasound is provided.

I.p. injection (5 g crude drug/kg) of water extract of Salvia miltiorrhiza to S.D. rats can prevent the acute cardial ischemia induced by the ligation of the coronary artery. The elevation of S-T segment in the electrocardiogram caused by the ischemia was greatly reduced in animals treated with Salvia miltiorrhiza compared with control group. The ischemia area in the left ventricle was significantly reduced and survival rate of the rats increased.

Acute fatal ventricular fibrillation (VF) in male Sprague-Dawley rats was induced by subcutaneous injection of isoproterenol (1 mg or 5 mg/kg body weight) to two groups of rats of different body weights (525 +/- 21 g or 387 +/- 11 g) respectively. VF occurred in all control rats resulting in 96% death with only 4% spontaneously reverted and survived. Pretreatment of animals, with or without pentobarbital anaesthesia, with an aqueous extract of Salvia miltiorrhiza (SM-H, i.p., 5 g herb/kg body weight) significantly reduced J-point displacement and VF induced by isoproterenol. Survival rate was significantly raised compared with the control (P less than 0.05). Immediate intravenous injection of SM-H (5 g herb/kg body weight) to poisoned rats which developed VF caused 71% of them to recover temporarily their sinus rhythm and significantly prolonged their survival time (P less than 0.05).

Aqueous extract of Salvia miltiorrhiza (SM-H) can protect the acute myocardial ischemia and arrhythmia of Sprague-Dawley rats induced by isoproterenol (ISO) or BaCl2 with the following results: (1) intraperitoneal injection (i.p.) of SM-H for 3 to 5 days or intravenously (i.v.) just once significantly reduced the death rate of the animals, (2) i.v. SM-H pretreatment significantly increased the lethal dose of BaCl2 infusion, (3) i.p. SM-H significantly decreased premature ventricular contraction, ventricular fibrillation, bradycardia and mortality rate induced by bolus i.v. of BaCl2, and (4) i.p. SM-H also significantly reduced ECG J-point displacement of rats induced by ISO.