Systematic review of bovine and zoonotic tuberculosis in the Western Pacific and the Southeast Asia regions of the World Health Organization.

Introduction: Tuberculosis (TB) remains a leading cause of mortality worldwide. We conducted this systematic review to understand the distribution of bovine and zoonotic tuberculosis in the World Health Organization (WHO)'s Southeast Asia Region (SEAR) and Western Pacific Region (WPR) to inform our understanding of the risk posed by this disease. Methods: A two-pronged strategy was used by evaluating data from peer-reviewed literature and official reports. A systematic search was conducted using a structured query in four databases (Web of Science, Scopus, Medline, and PubMed) to identify any reports of the occurrence of zoonotic TB. No language and time constraints were used during the search, but non-English language articles were later excluded. The official data were sourced from the World Organization for Animal Health's (WOAH) World Animal Health Information System (WAHIS) and WHO's global TB database. Results: The retrieved records from SEAR and WPR (n = 113) were screened for eligibility, and data about disease occurrence were extracted and tabulated. In SEAR, all of the five studies that conducted Mycobacterium speciation (5/6) in humans were from India, and the reported Mycobacterium species included M. tuberculosis, M. bovis, M. scrofulacium, M. kansasii, M. phlei, M. smegmatis and M. orygis. In WPR, Mycobacterium speciation investigations in humans were conducted in Australia (8), China (2), Japan (2), NewZealand (2) and Malaysia (1), and the reported Mycobacterium species included M. bovis, M. africanum and M. tuberculosis. Seven countries in WHO's SEAR have officially reported the occurrence of Mycobacterium bovis in their animals: Bangladesh, India, Indonesia, Myanmar, Nepal, Sri Lanka and Thailand. In WPR, the WAHIS information system includes reports of the identification of M. bovis from 11 countries - China, Fiji, Japan, Malaysia, Mongolia, New Zealand, the Philippines, the Republic of Korea, Singapore, Tonga and Viet Nam. In contrast, human zoonotic TB cases in the WHO database were only listed from Australia, Brunei Darussalam and Palau countries. Discussion: The available data suggests under-reporting of zoonotic TB in the regions. Efforts are required to strengthen zoonotic TB surveillance systems from both animal and human health sides to better understand the impact of zoonotic TB in order to take appropriate action to achieve the goal of ending the TB epidemic.

Securement to Prevent Noncuffed Central Venous Catheter Dislodgement in Pediatrics: The SECURED Superiority Randomized Clinical Trial.

Importance: Catheter dislodgement is a common complication for children with tunneled or peripherally inserted noncuffed central venous catheters (CVCs). A subcutaneous anchor securement system (SASS) may reduce this risk compared with traditional adhesive securement. Objective: To compare dislodgement of noncuffed CVCs secured with SASS with dislodgement of noncuffed CVCs secured with sutureless securement devices (SSDs). Design, Setting, and Participants: The SECURED (Securing Central Venous Catheters to Prevent Dislodegment) trial was a pragmatic, multicenter, superiority randomized clinical trial with an internal pilot and was conducted from August 5, 2020, to August 30, 2022, at 2 Australian quaternary pediatric hospitals. Data analysis was performed in January 2023. Patients aged 0 to 18 years requiring a noncuffed CVC (≥3F catheter) were eligible for inclusion. Follow-up duration was 8 weeks or until device removal. Interventions: Patients were randomly assigned 1:1 to receive an SASS or SSD, stratified by hospital and catheter type. Only 1 catheter was studied per patient. Main Outcomes and Measures: The primary outcome was dislodgement (partial or total), defined as movement of the catheter tip by greater than 1 cm (change in external catheter length) at any point during catheter dwell. Dislodgement, reported as a risk ratio (RR), was estimated using a generalized linear model with binomial family and log link. Secondary outcomes were reported as incidence rate ratios and were analyzed using Poission regression. Outcomes reported as mean differences (MDs) were analyzed using linear regression. Results: Of 310 randomized patients, 175 patients (56.5%) were male and median (IQR) patient age was 48 (16-120) months. A total of 307 patients had a catheter device inserted, of which 153 (49.8%) were SASS and 154 (50.2%) were SSD, and were included in the intention-to-treat (ITT) analysis. Device dislodgement was lower with SASS (8 dislodgements in 153 patients [5.2%]) compared with SSD (35 dislodgements in 154 patients [22.7%]) (RR, 0.23; 95% CI, 0.11-0.48; P < .001). The per-protocol analysis was consistent with the ITT analysis. Partial dislodgement accounted for most dislodgement events, including 6 partial dislodgements in the SASS group (3.9%) and 30 partial dislodgements in the SSD group (19.5%) (RR, 0.18; 95% CI, 0.08-0.42). This contributed to fewer complications during dwell in the SASS group (37 reported complications [24.2%]) vs the SSD group (60 reported complications [39.0%]) (RR, 0.62; 95% CI, 0.44-0.87). Staff reported greater difficulty removing devices anchored with SASS vs SSD (mean [SD], 29.1 [31.3] vs 5.3 [17.0], respectively; MD, 23.8; 95% CI, 16.7-31.0). However, use of SASS resulted in reduced per-participant health care costs of A$36.60 (95% credible interval, 4.25-68.95; US $24.36; 95% credible interval, 2.83-45.89). Conclusions and Relevance: In the SECURED trial, noncuffed CVCs secured with SASS had fewer dislodgements compared with SSDs, with a lower cost per patient and an acceptable safety profile. Future efforts should be directed at SASS implementation at the health service level. Trial Registration: anzctr.org.au Identifier: ACTRN12620000783921.

Performance of tunnelled, non-cuffed central venous catheters in infants: A scoping review.

AIM: To summarise and critique existing knowledge and evidence relating to the utility, and post-insertion complications surrounding tunnelled non-cuffed central venous catheters (tncCVCs) in infants. METHODS: A scoping review of original research studies reporting the use of, and post-insertion complications associated with, tncCVCs in infants was completed. MeSH terms were used to formulate a systematic search, and data were extracted using a customised data extraction form. Data were analysed descriptively across key themes based on the research questions. Study quality was evaluated using the Mixed Methods Appraisal Tool. RESULTS: The systematic search generated 3994 studies, of which 9 studies met final inclusion criteria. Studies included 644 tncCVCs in infants based in the USA, Europe and Australia. Most studies were retrospective cohort studies. The most common vein of insertion, where individually specified, was the internal jugular (n = 177). Tunnel length, where reported, was 2.5-5 cm. Infection rates were most commonly reported (eight studies), with results ranging from 0 to 12.8%, and device dislodgements of up to 20% reported. Participant follow-up and definition of complications varied greatly between studies. Study quality across all papers was sound. CONCLUSIONS: This review has identified only a small number of studies, with small participant numbers, reporting the performance of tncCVCs in infants. Definitions of complications measured varied significantly between studies, and vastly different patient follow-up protocols were reported. Further larger-scale studies on the performance of tncCVC, employing internationally recognised reporting standards is warranted to ensure clinicians can make informed choices for medication and infusion delivery.

Global burden of disease due to rifampicin-resistant tuberculosis: a mathematical modeling analysis.

In 2020, almost half a million individuals developed rifampicin-resistant tuberculosis (RR-TB). We estimated the global burden of RR-TB over the lifetime of affected individuals. We synthesized data on incidence, case detection, and treatment outcomes in 192 countries (99.99% of global tuberculosis). Using a mathematical model, we projected disability-adjusted life years (DALYs) over the lifetime for individuals developing tuberculosis in 2020 stratified by country, age, sex, HIV, and rifampicin resistance. Here we show that incident RR-TB in 2020 was responsible for an estimated 6.9 (95% uncertainty interval: 5.5, 8.5) million DALYs, 44% (31, 54) of which accrued among TB survivors. We estimated an average of 17 (14, 21) DALYs per person developing RR-TB, 34% (12, 56) greater than for rifampicin-susceptible tuberculosis. RR-TB burden per 100,000 was highest in former Soviet Union countries and southern African countries. While RR-TB causes substantial short-term morbidity and mortality, nearly half of the overall disease burden of RR-TB accrues among tuberculosis survivors. The substantial long-term health impacts among those surviving RR-TB disease suggest the need for improved post-treatment care and further justify increased health expenditures to prevent RR-TB transmission.

Midline Compared With Peripheral Intravenous Catheters for Therapy of 4 Days or Longer in Pediatric Patients: A Randomized Clinical Trial.

Importance: Peripheral intravenous catheters (PIVCs) frequently fail during treatment causing therapy interruption, pain, recatheterization, and additional health care costs. Midline catheters (MCs) may improve functional dwell time and reduce failure compared with traditional PIVCs. Objective: To compare device failure of MCs with PIVCs. Design, Setting, and Participants: This was a pragmatic, randomized clinical superiority trial with an embedded internal pilot study conducted from July 2020 to May 2022. The study took place in a quaternary pediatric hospital in Brisbane, Queensland, Australia. Inclusion criteria were patients aged 1 to 18 years requiring peripherally compatible intravenous therapy for 4 days or longer. Interventions: Patients were randomly assigned 1:1 to receive a PIVC or MC, stratified by age (≤5 years, >5 years). One catheter was studied per patient. Main Outcomes and Measures: The primary outcome was all-cause device failure, defined as premature cessation of device function. Secondary outcomes included number of insertion attempts, insertion failure, pain (on insertion), procedural time, patient/parent satisfaction (with insertion), device dwell time, device complications during dwell time, additional vascular access devices required to complete treatment, clinician satisfaction (at removal), and health care costs. Results: Of the 128 patients randomly assigned to study groups, 127 patients (median [IQR] age, 7 [2-13] years; 71 male [56%]) had a device inserted, with 65 (51.2%) in the PIVC group and 62 (48.8%) in the MC group. All patients were included in the intention-to-treat analysis. Device failure was lower in patients in the MC group (10 [16.1%]) compared with those in the PIVC group (30 [46.2%]; odds ratio [OR], 0.22; 95% CI, 0.10-0.52; P <.001). MCs were associated with fewer insertion attempts (mean difference [MD], -0.3; 95% CI, -0.5 to 0; P = .04), increased dwell time (MD, 66.9 hours; 95% CI, 36.2-97.5 hours; P <.001), and fewer patients required additional vascular access devices to complete treatment in the MC group (4 [6.5%]) and PIVC group (19 [29.2%]; OR, 0.17; 95% CI, 0.05-0.52; P = .002). Compared with PIVCs, use of MCs was associated with greater patient (9.0 vs 7.1 of 10; P = .002) and parent (9.1 vs 8.2 of 10; P = .02) satisfaction and lower health care costs (AUS -$151.67 [US -$101.13] per person; 95% credible interval, AUS -$171.45 to -$131.90 [US -$114.20 to -$87.95]). Conclusions and Relevance: Findings suggest that MC insertion for patients requiring peripherally compatible intravenous therapy for 4 days or longer should be prioritized to reduce the resource intensive, expensive, and burdensome sequelae of device failure. Trial Registration: Australia New Zealand Clinical Trials Registry, ACTRN12620000724976.

Secondhand Smoke Exposure Inside the Home Among Adults in Eight Countries in Sub-Saharan Africa: Global Adult Tobacco Survey, 2012-2018.

INTRODUCTION: Secondhand tobacco smoke (SHS) exposure causes diseases and death in adults and children. Evidence indicates that most SHS exposures occur at home and in the workplace. Therefore, home is a major place where adults and children can be effectively protected from SHS. This study examined the magnitude of SHS exposure at home and associated factors in eight sub-Saharan African countries. AIMS AND METHODS: We analyzed 2012-2018 Global Adult Tobacco Survey data for Botswana, Cameroon, Ethiopia, Kenya, Nigeria, Senegal, Tanzania, and Uganda. We computed prevalence estimates of self-reported monthly SHS exposure at home reported as anyone smoking inside their home daily, weekly, or monthly. We calculated SHS exposure at home prevalence and applied multivariable logistic regression models to identify related factors. RESULTS: Overall median prevalence of SHS exposure at home was 13.8% in the eight countries; ranging from 6.6% (95% CI: 5.7%, 7.6%) in Nigeria to 21.6% (95% CI: 19.4%, 24.0%) in Senegal. In multivariable analysis across the countries, SHS exposure at home was associated with living with a smoker, ranging from an adjusted odds ratio (AOR) of 4.6 (95% CI: 3.6, 5.8) in Botswana to 27.6 (95% CI: 20.1, 37.8) in Nigeria. SHS exposure at home was significantly associated with lower education attainment (Kenya and Ethiopia), and lower wealth index (Uganda, Senegal, and Botswana). CONCLUSIONS: SHS exposure in homes was associated with the presence of a smoker in the home and lower socioeconomic status.

Electronic cigarette use among adults in 14 countries: A cross-sectional study.

Background: The tobacco product landscape continues to change. No recent data for electronic cigarette (e-cigarette) use have been reported for multiple countries based on nationally representative surveys. We examined prevalence of e-cigarette use and variations by sociodemographic characteristics in 14 countries using Global Adult Tobacco Survey (GATS) data between Jan 1, 2015, and Dec 31, 2018. Methods: GATS is a nationally representative household survey of tobacco use among adults aged ≥15 years. The analytic sample size ranged from 4347 in Senegal to 74,037 in India. Prevalence of current e-cigarette use was stratified by sociodemographic subgroups. Age-standardized prevalence was estimated according to world 2000-2025 standard population. Significant differences in adjusted prevalence across sociodemographic subgroup was determined by p value for marginal effect contrast in multivariable logistic regression models. Findings: More than 50% of adults in Russia, Romania, and Ukraine and additionally more than 30% of adults in China, Costa Rica, Uruguay, Mexico, and Philippines were aware of e-cigarettes. Crude prevalence of current e-cigarette use ranged from 0.02% (95% CI 0.01%-0.04%) in India to 3.5% (2.9%-4.2%) in Russia. Prevalence was <1% in nine countries. Approximately 18.3 million adults currently used e-cigarettes across the 14 countries. Men had a significantly higher prevalence of current e-cigarette use than women in eight countries. Additionally, higher adjusted prevalence was observed in some countries among young adults aged 15‒24 years, urban residents, and adults with higher education levels and higher wealth index. Interpretation: The study provides needed baseline data on e-cigarette awareness and use. Continued surveillance is essential to inform interventions and policies to prevent initiation and enhance cessation support. Funding: None.

Experience on the first national anti-TB drug resistance survey (DRS) in Timor-Leste.

BACKGROUND: A national drug resistance survey (DRS) was implemented for the first time in Timor-Leste (TL) in 2019. The primary objective of the survey was to assess the prevalence of drug resistance among new and previously treated pulmonary TB patients in the country. METHODS: This nation-wide cross-sectional survey was conducted in 2019 targeting all new and previously treated sputum smear-positive pulmonary TB patients. Sputum samples were submitted to the National TB Reference Laboratory for confirmation of TB and to determine resistance to rifampicin by Xpert MTB/RIF. Culture was performed on solid media, and culture isolates of confirmed TB cases were shipped to the WHO Supranational TB Reference Laboratory in Chennai, India for whole genome sequencing (WGS). Survey summary statistics, data cross-tabulations and analysis of potential risk factors of rifampicin-resistant TB (RR-TB) were conducted using R statistical software (version 3.5.2). RESULTS: A total of 953 sputum-smear positive patients were enrolled, of which 917 were confirmed as positive for TB by either Xpert MTB/RIF or culture. An electronic web-based system was used for entry and storage of the data. Rifampicin resistance was detected among 0.6% (95% CI 0.2-1.3) of new cases and 2.7% (95% CI 0.5- 8.2) of previously treated cases. WGS was conducted for validation purposes on 65 randomly selected isolates (29% of RR-TB (2/7) and 7% of RS-TB (63/910) by Xpert MTB/RIF or pDST). The original test results agreed with the WGS validation results for 62/64 isolates (97%). CONCLUSION: The prevalence of RR-TB in Timor-Leste is relatively low compared to the estimated proportions of RR-TB in the WHO South-East Asia Region (2.5% [95% CI 1.9-3.3] among new cases and 14% [95% CI 7.7-21] among previously treated cases). The rapid sputum collection and transportation mechanism implemented in the survey demonstrates its feasibility in low resource settings and should be replicated for routinely transporting TB specimens from microscopy labs to GeneXpert sites. Establishment of in-country capacity for rapid molecular diagnostics for both first- and second-line DST is an immediate need for achieving universal drug susceptibility testing (DST) to guide appropriate patient management.

25 years of surveillance of drug-resistant tuberculosis: achievements, challenges, and way forward.

Tuberculosis is second only to COVID-19 as a cause of death from a single infectious agent. In 2020, almost 10 million people were estimated to have developed tuberculosis and it caused 1·5 million deaths. Around a quarter of deaths caused by antimicrobial resistance are due to rifampicin-resistant tuberculosis. Antimicrobial resistance surveillance systems for many bacterial pathogens are still in the early stages of implementation in many countries, and do not yet allow for the estimation of disease burden at the national level. In this Personal View, we present the achievements, challenges, and way forward for the oldest and largest global antimicrobial resistance surveillance system. Hosted by WHO since 1994, the Global Project on Anti-Tuberculosis Drug Resistance Surveillance has served as a platform for the evaluation of the trends in anti-tuberculosis drug resistance for over 25 years at country, regional, and global levels. With an estimated 465 000 incident cases of multidrug-resistant and rifampicin-resistant tuberculosis in 2019, drug-resistant tuberculosis remains a public health crisis. The COVID-19 pandemic has reversed years of progress in providing essential tuberculosis services and reducing disease burden. The number of people diagnosed with drug-resistant tuberculosis has dropped by 22% since before the pandemic, and the number of patients provided with treatment for drug-resistant tuberculosis has dropped by 15%. Now more than ever, closing gaps in the detection of drug-resistant tuberculosis requires investment in research and development of new diagnostic tools and their rollout, expansion of sample transport systems, and the implementation of data connectivity solutions.

Population structure, biogeography and transmissibility of Mycobacterium tuberculosis.

Mycobacterium tuberculosis is a clonal pathogen proposed to have co-evolved with its human host for millennia, yet our understanding of its genomic diversity and biogeography remains incomplete. Here we use a combination of phylogenetics and dimensionality reduction to reevaluate the population structure of M. tuberculosis, providing an in-depth analysis of the ancient Indo-Oceanic Lineage 1 and the modern Central Asian Lineage 3, and expanding our understanding of Lineages 2 and 4. We assess sub-lineages using genomic sequences from 4939 pan-susceptible strains, and find 30 new genetically distinct clades that we validate in a dataset of 4645 independent isolates. We find a consistent geographically restricted or unrestricted pattern for 20 groups, including three groups of Lineage 1. The distribution of terminal branch lengths across the M. tuberculosis phylogeny supports the hypothesis of a higher transmissibility of Lineages 2 and 4, in comparison with Lineages 3 and 1, on a global scale. We define an expanded barcode of 95 single nucleotide substitutions that allows rapid identification of 69 M. tuberculosis sub-lineages and 26 additional internal groups. Our results paint a higher resolution picture of the M. tuberculosis phylogeny and biogeography.

The burden of drug resistance tuberculosis in Ghana; results of the First National Survey.

Resistance to Tuberculosis drugs has become a major threat to the control of tuberculosis (TB) globally. We conducted the first nation-wide drug resistance survey to investigate the level and pattern of resistance to first-line TB drugs among newly and previously treated sputum smear-positive TB cases. We also evaluated associations between potential risk factors and TB drug resistance. Using the World Health Organization (WHO) guidelines on conducting national TB surveys, we selected study participants from 33 health facilities from across the country, grouped into 29 clusters, and included them into the survey. Between April 2016 and June 2017, a total of 927 patients (859 new and 68 previously treated) were enrolled in the survey. Mycobacterium tuberculosis complex (MTBC) isolates were successfully cultured from 598 (65.5%) patient samples and underwent DST, 550 from newly diagnosed and 48 from previously treated patients. The proportion of patients who showed resistance to any of the TB drugs tested was 25.2% (95% CI; 21.8-28.9). The most frequent resistance was to Streptomycin (STR) (12.3%), followed by Isoniazid (INH) (10.4%), with Rifampicin (RIF), showing the least resistance of 2.4%. Resistance to Isoniazid and Rifampicin (multi-drug resistance) was found in 19 (3.2%; 95% CI: 1.9-4.9) isolates. Prevalence of multidrug resistance was 7 (1.3%; 95% CI: 0.5-2.6) among newly diagnosed and 12 (25.0%; 95% CI: 13.6-39.6) among previously treated patients. At both univariate and multivariate analysis, MDR-TB was positively associated with previous history of TB treatment (OR = 5.09, 95% CI: 1.75-14.75, p = 0.003); (OR = 5.41, 95% CI: 1.69-17.30, p = 0.004). The higher levels of MDR-TB and overall resistance to any TB drug among previously treated patients raises concerns about adherence to treatment. This calls for strengthening existing TB programme measures to ensure a system for adequately testing and monitoring TB drug resistance.

Tobacco Smoking Cessation and Quitline Use Among Adults Aged ≥15 Years in 31 Countries: Findings From the Global Adult Tobacco Survey.

INTRODUCTION: About 80% of the 1.1 billion people who smoke tobacco worldwide reside in low- and middle-income countries. Evidence-based approaches to promote cessation include brief advice from health professionals and referrals through quitlines. This study assesses cessation behaviors and the use of cessation services in the past 12 months among current tobacco smokers in 31 countries who attempted to quit. METHODS: Data came from the Global Adult Tobacco Survey, a household-based survey of non-institutionalized adults aged ≥15 years. Surveys were conducted in 31 countries during 2008-2018; sample sizes ranged from 4,250 (Malaysia) to 74,037 (India), and response rates ranged from 64.4% (Ukraine) to 98.5% (Qatar). In 2019, data from the 31 countries were assessed in June 2019, and indicators included self-reported current (daily or less than daily) tobacco smoking, past-year quit attempts, and cessation methods used in the past 12 months. RESULTS: Current tobacco smoking prevalence ranged from 3.7% (Ethiopia) to 38.2% (Greece). Overall, an estimated 176.8 million adults from the 31 countries made a quit attempt in the past 12 months, with country-level prevalence ranging from 16.4% (Greece) to 54.7% (Botswana). Most individuals who made a quit attempt did so without assistance (median=74.4%). Other methods were less prevalent, including quitlines (median=0.2%) and counseling (median=7.2%). CONCLUSIONS: In the assessed countries, the majority of those who currently smoked tobacco and made a quit attempt did so without assistance; very few reported using quitlines, partly because of the lack of quitlines in some countries. In resource-limited settings, quitlines can play a greater role in helping people quit smoking as part of a comprehensive approach.

Ongoing challenges to understanding multidrug- and rifampicin-resistant tuberculosis in children versus adults.

Previous analyses suggest that children with tuberculosis (TB) are no more or no less likely to have multidrug (MDR)- or rifampicin-resistant (RR)-TB than adults. However, the availability of new data, particularly for high MDR/RR-TB burden countries, suggest updates of country-specific estimates are warranted.We used data from population-representative surveys and surveillance collected between 2000 and 2018 to compare the odds ratio of MDR/RR-TB among children (aged <15 years) with TB, compared to the odds of MDR/RR-TB among adults (aged ≥15 years) with TB.In most settings (45 out of 55 countries), and globally as a whole, there is no evidence that age is associated with odds of MDR/RR-TB. However, in some settings, such as former Soviet Union countries in general, and Georgia, Kazakhstan, Lithuania, Tajikistan and Uzbekistan in particular, as well as Peru, MDR/RR-TB is positively associated with age ≥15 years. Meanwhile, in Western Europe in general, and the United Kingdom, Poland, Finland and Luxembourg in particular, MDR/RR-TB is positively associated with age <15 years. 16 countries had sufficient data to compare over time between 2000-2011 and 2012-2018, with evidence for decreases in the odds ratio in children compared to adults in Germany, Kazakhstan and the United States of America.Our results support findings that in most settings a child with TB is as likely as an adult with TB to have MDR/RR-TB. However, setting-specific heterogeneity requires further investigation. Furthermore, the odds ratio for MDR/RR-TB in children compared to adults is generally either stable or decreasing. There are important gaps in detection, recording and reporting of drug resistance among paediatric TB cases, limiting our understanding of transmission risks and measures needed to combat the global TB epidemic.

Prevention of occlusion of cEnTral lInes for children with cancer: An implementation study.

AIM: Central venous access devices (CVADs) are vital medical devices to support the treatment of paediatric cancer; however, device occlusion is common, which disrupts treatment. This study aimed to improve the identification and management of CVAD occlusions in children with cancer, as well as to identify the demographic, clinical and device characteristics associated with increased risk for CVAD occlusion. METHODS: A pre-post-implementation study was conducted at a metropolitan paediatric oncology facility in Australia, using the Theoretical Domains Framework. Patients with a CVAD for anti-cancer therapy were prospectively followed for occlusive events pre- and post- the implementation of clinical resources to support the identification and management of CVAD occlusive events. CVAD occlusion and management data were collected and compared pre- and post-implementation. Risk factors for CVAD occlusion were described by mixed-effects Poisson regression and incident rate ratios (IRR). RESULTS: A total of 133 CVADs were inserted into 131 patients for a total of 6784 catheter days. The incidence of CVAD-related occlusion pre-implementation was 59.7 (95% confidence interval (CI) 51.4-69.0, per 1000 catheter days); compared to 31.6 (95% CI 26.4-37.6); P < 0.01) post-implementation of clinical resources. In multivariate models, other than post-implementation phases (IRR 0.51 (95% CI 0.32-0.81)), only neutropaenia significantly increased the risk of CVAD occlusion (IRR 2.14 (95% CI 1.15-3.97)). CONCLUSION: CVAD occlusions in paediatric oncology are common. The development and implementation of CVAD occlusion resources to guide the identification and management of occlusive episodes led to a significant decrease in occlusive events.

Targeted next-generation sequencing of sputum for diagnosis of drug-resistant TB: results of a national survey in Democratic Republic of the Congo.

The surveillance of drug resistance among tuberculosis (TB) patients is central to preventing the spread of antimicrobial resistance. The Democratic Republic of the Congo (DR Congo) is classified by the World Health Organization (WHO) as a country with a high burden of TB and multidrug-resistant TB (MDR-TB), but there are no nationally representative data on drug resistance. In 2016-2017, a national survey of TB patients was conducted in 108 microscopy centres across all 11 provinces of the country using innovative molecular approaches. Sputum samples were collected from 1,545 new and 163 previously treated patients. These were tested by the Xpert MTB/RIF assay, followed by targeted next-generation sequencing performed directly on sputum. The prevalence of rifampicin resistance was low, at 1.8% (95% CI: 1.0-3.2) among new and 17.3% (95% CI: 11.9-24.4) among previously treated patients. Resistance to pyrazinamide, fluoroquinolones and second-line injectables was also low. The prevalence of resistance to isoniazid among rifampicin-susceptible patients was higher, at 6.6% (95% CI: 4.4-9.8) among new and 8.7% (95% : 3.2-21.2) among previously treated patients. Diagnosing and treating isoniazid-resistant patients remains a challenge, given that many will be missed by the current national diagnostic algorithm that is driven by detecting rifampicin resistance by Xpert MTB/RIF. This is the first nationwide survey incorporating targeted sequencing directly on sputum. It serves as a proof-of-concept for other settings that do yet have rapid specimen transport networks or capacity to conduct culture.

The risk of multidrug- or rifampicin-resistance in males versus females with tuberculosis.

Males are at an increased risk of tuberculosis (TB) disease compared to females. Additionally, several risk factors for multidrug-resistant (MDR) or rifampicin-resistant (RR) TB disease are more common in males, hence male TB patients may have a higher relative risk of MDR/RR-TB than female TB patients.We used sex-disaggregated data of TB patients reported to the World Health Organization for 106 countries to calculate male-to-female (M:F) risk ratios of having MDR/RR-TB.There was no evidence of either sex being more at risk of MDR/RR-TB in 81% (86 out of 106) of countries, with an overall random-effects weighted M:F risk ratio of 1.04 (95% CI 0.97-1.11). In 12% (13 out of 106) of countries there was evidence that males were more at risk, while in 7% (seven out of 106), females were more at risk. The risk of having TB that was MDR/RR increased for males compared to females as MDR/RR-TB incidence increased, and was higher for males than females in the former Soviet Union, where the risk ratio was 1.16 (1.06-1.28). Conversely, the risk increased for females compared to males as gross domestic product purchase power parity increased, and was higher for females than males in countries where the majority of TB burden was found in the foreign-born population, where the risk ratio was 0.84 (0.75-0.94).In general, the risk of MDR/RR-TB, among those with TB, is the same for males as for females. However, males in higher MDR/RR-TB burden countries, particularly the former Soviet Union, face an increased risk that their infection is MDR/RR-TB, highlighting the need for a sex-differentiated approach to TB case-finding and care.

Prevalence and genetic profiles of isoniazid resistance in tuberculosis patients: A multicountry analysis of cross-sectional data.

BACKGROUND: The surveillance of drug resistance among tuberculosis (TB) patients is central to combatting the global TB epidemic and preventing the spread of antimicrobial resistance. Isoniazid and rifampicin are two of the most powerful first-line anti-TB medicines, and resistance to either of them increases the risk of treatment failure, relapse, or acquisition of resistance to other drugs. The global prevalence of rifampicin resistance is well documented, occurring in 3.4% (95% CI 2.5%-4.4%) of new TB patients and 18% (95% CI 7.6%-31%) of previously treated TB patients in 2018, whereas the prevalence of isoniazid resistance at global and regional levels is less understood. In 2018, the World Health Organization (WHO) recommended a modified 6-month treatment regimen for people with isoniazid-resistant, rifampicin-susceptible TB (Hr-TB), which includes rifampicin, pyrazinamide, ethambutol, and levofloxacin. We estimated the global prevalence of Hr-TB among TB patients and investigated associated phenotypic and genotypic drug resistance patterns. METHODS AND FINDINGS: Aggregated drug resistance data reported to WHO from either routine continuous surveillance or nationally representative periodic surveys of TB patients for the period 2003-2017 were reviewed. Isoniazid data were available from 156 countries or territories for 211,753 patients. Among these, the global prevalence of Hr-TB was 7.4% (95% CI 6.5%-8.4%) among new TB patients and 11.4% (95% CI 9.4%-13.4%) among previously treated TB patients. Additional data on pyrazinamide and levofloxacin resistance were available from 6 countries (Azerbaijan, Bangladesh, Belarus, Pakistan, the Philippines, and South Africa). There were no cases of resistance to both pyrazinamide and levofloxacin among Hr-TB patients, except for the Philippines (1.8%, 95% CI 0.2-6.4) and Belarus (5.3%, 95% CI 0.1-26.0). Sequencing data for all genomic regions involved in isoniazid resistance were available for 4,563 patients. Among the 1,174 isolates that were resistant by either phenotypic testing or sequencing, 78.6% (95% CI 76.1%-80.9%) had resistance-conferring mutations in the katG gene and 14.6% (95% CI 12.7%-16.8%) in both katG and the inhA promoter region. For 6.8% (95% CI 5.4%-8.4%) of patients, mutations occurred in the inhA promoter alone, for whom an increased dose of isoniazid may be considered. The main limitations of this study are that most analyses were performed at the national rather than individual patient level and that the quality of laboratory testing may vary between countries. CONCLUSIONS: In this study, the prevalence of Hr-TB among TB patients was higher than the prevalence of rifampicin resistance globally. Many patients with Hr-TB would be missed by current diagnostic algorithms driven by rifampicin testing, highlighting the need for new rapid molecular technologies to ensure access to appropriate treatment and care. The low prevalence of resistance to pyrazinamide and fluoroquinolones among patients with Hr-TB provides further justification for the recommended modified treatment regimen.

Tobacco Use and Tobacco-Related Behaviors - 11 Countries, 2008-2017.

Each year, tobacco use is responsible for approximately 8 million deaths worldwide, including 7 million deaths among persons who use tobacco and 1.2 million deaths among nonsmokers exposed to secondhand smoke (SHS) (1). Approximately 80% of the 1.1 billion persons who smoke tobacco worldwide reside in low- and middle-income countries (2,3). The World Health Organization's (WHO's) Framework Convention on Tobacco Control (FCTC) provides the foundation for countries to implement and manage tobacco control through the MPOWER policy package,* which includes monitoring tobacco use, protecting persons from SHS, warning them about the danger of tobacco, and enforcing bans on tobacco advertising, promotion, or sponsorship (tobacco advertising) (4). CDC analyzed data from 11 countries that completed two or more rounds of the Global Adult Tobacco Survey (GATS) during 2008-2017. Tobacco use and tobacco-related behaviors that were assessed included current tobacco use, SHS exposure, thinking about quitting because of warning labels, and exposure to tobacco advertising. Across the assessed countries, the estimated percentage change in tobacco use from the first round to the most recent round ranged from -21.5% in Russia to 1.1% in Turkey. Estimated percentage change in SHS exposure ranged from -71.5% in Turkey to 72.9% in Thailand. Estimated percentage change in thinking about quitting because of warning labels ranged from 77.4% in India to -33.0% in Turkey. Estimated percentage change in exposure to tobacco advertising ranged from -66.1% in Russia to 44.2% in Thailand. Continued implementation and enforcement of proven tobacco control interventions and strategies at the country level, as outlined in MPOWER, can help reduce tobacco-related morbidity and mortality worldwide (3,5,6).

Skin Complications Associated With Pediatric Central Venous Access Devices: Prevalence, Incidence, and Risk.

Central venous access devices (CVADs) are vital to enable treatment for children with cancer and other complex health conditions. However, complications effecting the CVAD wound are commonly reported. This study aimed to identify the incidence and prevalence of CVAD-associated skin complications current management, and characteristics associated with complication development, in pediatrics. A prospective observational study performed across medical, oncology, and hematology departments at a tertiary pediatric hospital in Australia, between April and July 2017. Children admitted with CVADs were assessed twice weekly for CVAD-associated skin complications and associated signs and symptoms. The data were analyzed using descriptive statistics (i.e., proportions, frequency) and time-to-event multivariable regression (i.e., hazard ratios [HRs]). Two hundred and seventy-one CVADs were reviewed over 43,787 catheter days, with over one eighth of participants (14%; n = 37) having a CVAD-associated skin complication during their admission (0.95 per 1,000 catheter days, 95% confidence interval [CI; 0.61, 1.17]), most commonly contact dermatitis (11%; n = 29; 0.72 per 1,000 catheter days 95% CI [0.50, 1.04]). Within biweekly checks the median point prevalence of complications varied between 0.4% and 11% and clinical management was wide-ranging. A primary diagnosis of oncology (HR 2.89, 95% CI [1.10, 7.62]) or medical/surgical (HR 2.55, 95% CI [1.04, 6.22]) conditions; plain, nonbordered polyurethane dressings (HR 4.92, 95% CI [2.00, 12.13]); and poor dressing integrity (HR 2.64, 95% CI [1.18, 5.92]) were significantly associated with contact dermatitis. In conclusion, substantial numbers of pediatric patients experience CVAD-associated skin complications, and innovations are necessary to identify, prevent, and treat these health care-associated injuries.