Trends in and Risk Factors for Drug Resistance in Mycobacterium tuberculosis in HIV-Infected Patients.

Trends in and risk factors for drug resistance in Mycobacterium tuberculosis (M. tuberculosis) in human immunodeficiency virus (HIV)-infected patients with active tuberculosis were analyzed. The clinical data of M. tuberculosis and HIV-coinfected patients treated at the Shanghai Public Health Clinical Center between 2010 and 2022 were collected. The diagnosis of tuberculosis was confirmed by solid or liquid culture. The phenotypic drug susceptibility test was carried out via the proportional method, and the resistance to first-line and second-line drugs was analyzed. Logistic regression analysis was performed to identify associated risk factors for drug resistance in M. tuberculosis. Of the 304 patients with a M. tuberculosis-positive culture and first-line drug susceptibility test results, 114 (37.5%) were resistant to at least one first-line anti-tuberculosis drug. Of the 93 patients with first-line and second-line drug susceptibility test results, 40 (43%) were resistant to at least one anti-tuberculosis drug, and 20 (21.5%), 27 (29.0%), 19 (20.4%), 16 (17.2%), and 14 (15.1%) were resistant to rifampicin, streptomycin, ofloxacin, levofloxacin, and moxifloxacin, respectively; 17 patients (18.3%) had multidrug-resistant tuberculosis (MDR-TB). Between 2010 and 2021, the rate of resistance to streptomycin and rifampicin ranged from 14.3% to 40.0% and from 8.0% to 26.3%, respectively, showing an increasing trend year by year. From 2016 to 2021, the rate of resistance to quinolones fluctuated between 7.7% and 27.8%, exhibiting an overall upward trend. Logistic regression analysis showed that being aged <60 years old was a risk factor for streptomycin resistance, mono-drug resistance, and any-drug resistance (RR 4.139, p = 0.023; RR 7.734, p = 0.047; RR 3.733, p = 0.009). Retreatment tuberculosis was a risk factor for resistance to rifampicin, ofloxacin, of levofloxacin (RR 2.984, p = 0.047; RR 4.517, p = 0.038; RR 6.277, p = 0.014). The drug resistance rates of M. tuberculosis to rifampicin and to quinolones in HIV/AIDS patients were high and have been increasing year by year. Age and a history of previous anti-tuberculosis treatment were the main factors associated with the development of drug resistance in HIV/AIDS patients with tuberculosis.

Postschool Goal Expectations for Youth With Intellectual and Developmental Disabilities.

Using National Longitudinal Transition Study 2012 data, this study explored parent and youth expectations in the areas of postsecondary education, employment, independent living, and financial independence. Compared to youth with other disabilities, youth with intellectual and developmental disabilities and their parents had much lower expectations for the four postschool goals, and parent expectations were much lower than youth's own expectations. Also, youth's race, along with their daily living skills and functional abilities, were positively associated with parent and youth expectations in several future goal areas. Our discussion highlights implications for improving the transition experiences of youth with intellectual and developmental disabilities.

Academia's responses to crisis: A bibliometric analysis of literature on online learning in higher education during COVID-19.

This paper aimed to provide a holistic view of research that investigated online learning in higher education around the globe during COVID-19 utilizing a bibliometric analysis. The researchers used co-citation analysis and text mining afforded by VOSviewer to document and analyze research patterns and topics reported in peer-reviewed documents published between January 2020 and August 2021. Findings of this study indicated that scholars from 103 countries or regions from the Global North and Global South investigated a wide array of topics, such as use of various technologies and strategies, redesigned curriculum, student perceptions and psychological impacts of the pandemic-imposed online learning. Many researchers applied technology acceptance theories and structural equation modeling to investigate factors associated with adoption and impacts of the pandemic-imposed online learning. Of the large quantity of research, medical education and chemical education were the most investigated disciplines. Inquiry-based learning, discovery learning, hands-on learning and collaborative learning emerged as instructional approaches frequently discussed or utilized across the target studies. This paper discussed (a) ongoing and emerging challenges to online higher education, (b) placing innovative pedagogies at the forefront of online learning, and (c) rapid, but imbalanced distribution of evolving literature based on the findings.

Psychometric Properties of Self-Determination Inventory: Student Report Among Chinese Students With and Without Intellectual and Developmental Disabilities.

This study explores the psychometric properties of Self-Determination Inventory: Student Report (SDI:SR) in students with intellectual and developmental disabilities (IDD) and without disabilities in China. The paper-and-pencil version of SDI:SR Chinese Translation (SDI:SR Chinese) was used to explore self-determination across students with IDD (n = 245) and students without disabilities (n = 315) from 16 schools across six cities in China. We examined the factor structure of the measure, conducted analysis of measurement invariance, and compared the latent means across students with IDD and without disabilities. Findings suggest that the data fit a one-factor model better than a three-factor model. We found greater variability in self-determination among students with IDD than students without disabilities. However, the two groups did not differ in latent means.

'I feel valued': the experience of social networking site engagement among people with intellectual and developmental disabilities in South Korea.

Previous studies have shown that participation in social networking sites (SNSs) enhances users' knowledge, social capital, and quality of life. However, people with intellectual developmental disabilities (PIDD) do not use SNSs to the same extent as the general population does. This study aimed to explore the experiences of those PIDD in South Korea who use social media. Data were collected through face-to-face interviews with 20 PIDD. The study participants reported benefits associated with the use of SNSs, which included enhanced social capital, self-confidence, and positive self-image. Participants also used SNSs to maintain friendships, initiate new relationships, and engage in self and community advocacy. Safety concerns were also reported by the participants. The study concluded that SNSs can be used as tools for promoting community inclusion and developing social capital for PIDD. However, the outcomes of using SNSs depend on the availability of support provided by one's network. The absence of support may result in frustration and even exploitation. With effective support, SNSs become powerful tools that can be used by PIDD to combat social isolation through creating ample opportunities for social inclusion.

Antimicrobial susceptibility profiles of Mycobacterium abscessus complex isolates from respiratory specimens in Shanghai, China.

OBJECTIVES: The aim of this study was to compare the antibiotic susceptibility profiles of Mycobacterium abscessus complex (MABC) isolates and to investigate the relationship between susceptibility profiles and genetic mechanisms of macrolide resistance. METHODS: More than 200 isolates collected from respiratory specimens between 2014 and 2018 were randomly analysed in this study. Minimum inhibitory concentrations (Mics) of ten potential antimicrobial agents were determined by the microplate alamarBlue assay. RESULTS: We identified 43 MABC isolates, including 32 M. abscessus subsp. abscessus (M. abscessus) (6 from immunocompromised patients) and 11 M. abscessus subsp. massiliense (M. massiliense). The majority of MABC isolates were susceptible to amikacin (96.9% and 100.0% for M. abscessus and M. massiliense, respectively), linezolid (96.9% and 100.0%, respectively), cefoxitin (100.0% and 100.0%, respectively), imipenem (90.6% and 72.7%, respectively) and tobramycin (90.6% and 72.7%, respectively). The resistance rates to clarithromycin and doxycycline in isolates of M. abscessus (68.8% and 100.0%) were significantly higher than those in isolates of M. massiliense (18.2% and 63.6%) (P < 0.05), whereas the percentage of tobramycin-resistant isolates among M. abscessus (9.4%) was significantly lower than among M. massiliense (27.3%) (P = 0.007). Sequencing analyses showed significant differences between erm(41) of M. abscessus and M. massiliense. CONCLUSION: Mycobacterium abscessus is the dominant pathogen of pulmonary MABC infections in our hospital. Aminoglycosides (amikacin and tobramycin), ß-lactams (cefoxitin and imipenem) and linezolid exhibited potent inhibitory activity against MABC in vitro. The erm(41) gene may be a promising marker to predict macrolide susceptibility for M. abscessus.

Stool-based Xpert MTB/RIF Ultra assay as a tool for detecting pulmonary tuberculosis in children with abnormal chest imaging: A prospective cohort study.

OBJECTIVES: To evaluate the diagnostic efficacy of stool-based Xpert MTB/RIF Ultra assay versus other assays for the detection of paediatric pulmonary tuberculosis (PTB). METHODS: A prospective head-to-head comparative study was conducted from Dec 2017 to May 2019 in Shanghai Public Health Clinical Centre. Samples were collected from children (< 15 years) with abnormal chest imaging (X-ray or CT scan) results for the following tests: Ultra on stool sample (Ultra-Stool), Ultra on respiratory tract sample (Ultra-RTS), Xpert MTB/RIF assay (Xpert) on RTS (Xpert-RTS), acid-fast bacilli smear on RTS (AFB-RTS), and Mycobacterium tuberculosis (Mtb) culture on RTS (Culture-RTS). The results were compared with a composite reference standard. RESULTS: A total of 126 cases with paired results were analysed. Against a composite reference standard, Ultra-RTS demonstrated the highest sensitivity (52%) and specificity (100%). Ultra-Stool showed 84.1% concordance with Ultra-RTS, demonstrating 45.5% sensitivity and 94.7% specificity (kappa = 0.65, 95% CI= 0.51-0.79). The sensitivity of Ultra-Stool was similar to Mtb culture (45.5%, p = 1.000) and higher than AFB-RTS (27.3%, p < 0.05). Assay positivity was associated with age and infiltration range in chest imaging. CONCLUSIONS: When RTS is difficult to obtain, stool sample-based Ultra is a comparable alternative.

Incidence and risk factors of delirium after percutaneous coronary intervention in individuals hospitalised for acute myocardial infarction: protocol for a systematic review and meta-analysis.

INTRODUCTION: Delirium in the postoperative period is a wide-reaching problem that affects important clinical outcomes. The incidence and risk factors of delirium in individuals with acute myocardial infarction (AMI) after primary percutaneous coronary intervention (PCI) has not been completely determined and no relevant systematic review and meta-analysis of incidence or risk factors exists. Hence, we aim to conduct a systematic review and meta-analysis to ascertain the incidence and risk factors of delirium among AMI patients undergoing PCI. METHODS AND ANALYSES: We will undertake a comprehensive literature search among PubMed, EMBASE, Cochrane Library, PsycINFO, CINAHL and Google Scholar from their inception to the search date. Prospective cohort and cross-sectional studies that described the incidence or at least one risk factor of delirium will be eligible for inclusion. The primary outcome will be the incidence of postoperative delirium. The quality of included studies will be assessed using a risk of bias tool for prevalence studies and the Cochrane guidelines. Heterogeneity of the estimates across studies will be assessed. Incidence and risk factors associated with delirium will be extracted. Incidence data will be pooled. Each risk factor reported in the included studies will be recorded together with its statistical significance; narrative and meta-analytical approaches will be employed. The systematic review and meta-analysis will be presented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. ETHICS AND DISSEMINATION: This proposed systematic review and meta-analysis is based on published data, and thus there is no requirement for ethics approval. The study will provide an up to date and accurate incidence and risk factors of delirium after PCI among patients with AMI, which is necessary for future research in this area. The findings of this study will be disseminated through publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020184388.

Performance of Xpert/MTB/RIF assay for childhood pulmonary tuberculosis among HIV negative children with real world evidence in China.

BACKGROUND: Rapid and accurate notification of childhood pulmonary tuberculosis (PTB) is a worldwide challenge. Although the Xpert MTB/RIF assay (Xpert) has been endorsed as the initial test for suspected PTB in many countries, limited studies have reported the performance of Xpert in childhood PTB. The aim of this study is to evaluate the real-world performance of Xpert for the detection of childhood PTB among HIV negative children in China. METHODS: We consecutively extracted the data of all patients ≤14 years with pulmonary disease through the electronic medical record (EMR) systems of Shanghai Public Health Clinical Center from January 2014 to December 2017. The clinical profile, the decision-making tests including AFB smear, solid/liquid culture, pathological examination and Xpert result were matched and assessed. The real diagnostic accuracy and the all-factors case notification rate for childhood PTB with the implementation of Xpert were evaluated. RESULTS: 519 HIV negative cases ≤14 years with pulmonary disease were extracted from the data base. Of these, 145 had matched results, there were 374 non-matched cases including 346 with incomplete or unavailable data and 28 with NTM, BCG or an unidentified strain. For matched data, the overall sensitivity and specificity of the Xpert assay were 66.7% (32/48, 95%CI 0.52-0.80) and 87.6% (85/97, 95%CI 0.87-0.98) respectively against the gold standard; 34.6% (44/127, 95%CI 26.6-43.7) and 100% against the composite clinical reference standard (CCRS). The all-factors case notification rate by Xpert was 29%. CONCLUSION: Xpert/MTB RIF assay has acceptable sensitivity and excellent specificity for rapid diagnosis of children with pulmonary TB as well as for the detection of RIF resistance in China. However, implementation of Xpert for the initial diagnosis of childhood PTB is inadequate to meet the urgent requirement for rapid and accurate detection of childhood PTB.

Adverse Childhood Experiences and Teen Sexual Behaviors: The Role of Self-Regulation and School-Related Factors.

BACKGROUND: There is limited evidence addressing the impact of adverse childhood experiences (ACEs) on adolescent sexual risk behaviors and pregnancy. In this study, we examined whether individual and cumulative ACEs increased the risk of unhealthy sexual behaviors and adolescent pregnancy. To inform intervention efforts, potential mediating mechanisms focusing on youth developmental assets were examined to explain the association. METHODS: Analyses included 88,815 (9th and 11th grade) students who completed the Minnesota Student Survey in the spring of 2016. RESULTS: Adolescents who reported each category of ACEs were more likely to initiate sex, have multiple sex partners, engage in unprotected sex, and be involved in pregnancy. Different youth assets, included self-regulation skills, connectedness to school, not skipping school, and academic performance, were associated with lower likelihood of sexual initiation and sexual risk-taking. They served as important mediators to reduce, though not completely diminish, the adverse effects of ACEs on sexual initiation and adolescent pregnancy. CONCLUSIONS: The results suggest that the relationship between ACEs and adolescent sexual risk behaviors and pregnancy is strong and graded. Effective school initiatives and intervention efforts should encourage the development of self-regulation and connectedness to school among teens who had been exposed to ACEs.

Mycobacterium tuberculosis clinical isolates carry mutational signatures of host immune environments.

Mycobacterium tuberculosis (Mtb) infection results in a spectrum of clinical and histopathologic manifestations. It has been proposed that the environmental and immune pressures associated with different contexts of infection have different consequences for the associated bacterial populations, affecting drug susceptibility and the emergence of resistance. However, there is little concrete evidence for this model. We prospectively collected sputum samples from 18 newly diagnosed and treatment-naïve patients with tuberculosis and sequenced 795 colony-derived Mtb isolates. Mutant accumulation rates varied considerably between different bacilli isolated from the same individual, and where high rates of mutation were observed, the mutational spectrum was consistent with reactive oxygen species-induced mutagenesis. Elevated bacterial mutation rates were identified in isolates from HIV-negative but not HIV-positive individuals, suggesting that they were immune-driven. These results support the model that mutagenesis of Mtb in vivo is modulated by the host environment, which could drive the emergence of variants associated with drug resistance in a host-dependent manner.

Active Support Training, Staff Assistance, and Engagement of Individuals With Intellectual and Developmental Disabilities in the United States: Randomized Controlled Trial.

Two non-U.S. quasi-experimental studies reported Active Support training was associated with increased engagement in individuals with IDD, but no randomized controlled trials (RCTs) exist. We evaluated effects of Active Support training on staff assistance, and social and nonsocial engagement in 75 individuals with intellectual and developmental disabilities (IDD) in U.S. group homes. We detected no significant effects of active support training. Individuals with more skills and less challenging behavior engaged more in nonsocial activities. Younger individuals with more skills living in homes with fewer staff changes were more socially engaged. Factors associated with nonsocial engagement mirrored those reported in Qian, Tichá, Larson, Stancliffe, & Wuorio, (2015) . Staffing-related implementation challenges and statistical power limited our ability to detect differences.

Predictors Associated With Paid Employment Status of Community and Technical College Students With Intellectual Disability.

The present study sought to identify predictors associated with paid employment outcomes for community and technical college students with intellectual disability (ID). Data used were collected from the Transition and Postsecondary Programs for Students With Intellectual Disabilities (TPSID) implemented in two community and technical colleges in the upper Midwest. The participants included 228 students with ID attending college who received supports based on the Check & Connect model. Results using logistic regression showed that students who only took inclusive classes, participated in campus events, had prior paid work experience, and participated in volunteering and/or community service were more likely to earn at or above minimum wage during their most recent year in the TPSID program. Implications for policy and practice are discussed.

Correction to: Routinely detected indicators in plasma have a predictive effect on the identification of HIV-infected patients with non-tuberculous mycobacterial and tuberculous infections.

CORRECTION: After publication of this article [1] it came to our attention that the affiliation of Jun Chen and Hong-zhou Lu were incorrectly shown.Jun Chen's affiliation should have been given as Department of Infectious Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.Hong-zhou Lu should have been given as Department of Infectious Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. Huashan Hospital affiliated to Fudan University, Shanghai, China. Medical College of Fudan University, Shanghai, China.The original article has been updated to reflect this change.

Routinely detected indicators in plasma have a predictive effect on the identification of HIV-infected patients with non-tuberculous mycobacterial and tuberculous infections.

BACKGROUND: It is difficult to quickly distinguish non-tuberculous mycobacterial (NTM) infection from tuberculosis (TB) infection in human immunodeficiency virus (HIV)-infected patients because of many similarities between these diseases. A simple and effective way to determine the differences using routine blood tests is necessary in developing countries. METHODS: A retrospective cohort study was conducted to recruit HIV-infected patients with either NTM infection or TB infection diagnosed for the first time according to mycobacterial culture and microscopic identification from May 2010 to March 2016. These data included the analysis of blood cells, liver function, renal function, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), and were compared between the HIV/TB and HIV/NTM groups. RESULTS: A total of 240 patients were enrolled. The number of HIV/TB and HIV/NTM patients was 113 and 127, respectively. There were no significant differences in the CD4 T-cell count, age, sex, percentage of patients initiating antiretroviral therapy (ART) before the explicit diagnosis of TB or NTM infection. NTM infection was more likely to be restricted in the pulmonary while TB infection also involves extra-pulmonary sites. Both the leukocyte count(5.60 × 109/L) and the proportion of neutrophils in the leukocyte count (76.70%) in the HIV/TB group were significantly higher than those in the HIV/NTM group (4.40 × 109/L [P = 0.0014] and 69.30% [P < 0.001]. The analysis of liver function markers indicated that the concentration of albumin but not ALT and AST was significantly lower in the HIV/TB group than in the HIV/NTM group (P < 0.001). The creatinine and urea levels were not significantly different between the two groups. The ESR (84.00 mm/h) and the concentration of CRP (59.60 mg/L) were significantly higher in the HIV/TB group than in the HIV/NTM group (52.00 mm/h and 19.60 mg/L, respectively) (P < 0.001). To distinguish TB infection from NTM infection, the best cut-off value was 69.5 mm/h for ESR, with a positive predictive value (PPV) of 0.740 and negative predictive value (NPV) of 0.721, and 48.8 mg/L for CRP, with a PPV of 0.676 and NPV of 0.697. CONCLUSION: The dissemination character as well as stronger immune response characterized by higher inflammation markers (e.g. WBC, ESR, CRP) can help distinguish TB from NTM infection in HIV-infected patients who need empirical therapy or diagnostic therapy immediately in low-income areas.

Pulmonary resection in the treatment of multidrug-resistant tuberculosis: A case series.

Multidrug-resistant (MDR) and extensive drug-resistant (XDR) tuberculosis (TB) are significant health problems throughout the world. Although the main treatment is medical, adjunctive surgical resection may increase the chance of cure in selected patients with MDR-TB or XDR-TB. This study aimed to present a case series of patients who underwent surgical resection for MDR-TB.Between March 2008 and November 2011, surgical resection was performed on 54 patients including 34 with MDR-TB and 20 with XDR-TB at the Departments of Surgery of Shanghai Public Health Clinical Center (Shanghai), Henan Chest Hospital (Henan), and Anhui Chest Hospital (Henan). Preoperative sputum smear samples were positive for 28 patients and sputum quantitative polymerase chain reaction was positive for 32. Patients were treated according to a standard therapy protocol for a mean of 4.2 months before the operation. The variables that affected treatment outcomes were identified through multivariate regression analysis.Fifty-four patients were operated for MDR-TB with localized disease usually complicated by cavity formation or destroyed lung. Thirty-seven were males and 17 were females. Median age was 37.8 (range, 20-75) years. Lobectomy was performed in 46 patients and pneumonectomy in 8. Muscle flaps were used in 36 of the patients with lobectomy and 8 with pneumonectomy. Various complications occurred in 6 (11.1%) patients, including bronchopleural fistula in 1 patient, bleeding in 2 patients, and prolonged air leak in 2 patients. A favorable outcome was achieved in 47 patients (87%) who underwent surgical resection. Higher body mass index (BMI) was associated with better outcome (odds ratio = 0.537, 95% confidence interval: 0.310-0.928, P = .026).Patients with MDR-TB had good treatment outcomes after adjunctive pulmonary resection, and with few complications. Higher BMI was related to a favorable outcome.

Molecular characterization of fluoroquinolone-resistant Mycobacterium tuberculosis clinical isolates from Shanghai, China.

China is one of the countries with the highest prevalence of fluoroquinolone-resistant (FQ(r)) Mycobacterium tuberculosis. Nevertheless, knowledge on the molecular characterization of the FQ(r)M. tuberculosis strains of this region remains very limited. This study was performed to investigate the frequencies and types of mutations present in FQ(r)M. tuberculosis clinical isolates collected in Shanghai, China. A total of 206 FQ(r)M. tuberculosis strains and 21 ofloxacin-sensitive (FQ(s)) M. tuberculosis strains were isolated from patients with pulmonary tuberculosis in Shanghai. The phenotypic drug susceptibilities were determined by the proportion method, and the mutations inside quinolone resistance-determining region (QRDR) of gyrA and gyrB genes were identified by DNA sequence analyses. Among 206 FQ(r)M. tuberculosis strains, 44% (90/206) were multidrug-resistant isolates and 39% (81/206) were extensively drug-resistant isolates. Only 9% (19/206) were monoresistant to ofloxacin. In total, 79.1% (163/206) of FQ(r) isolates harboured mutations in either gyrA or gyrB QRDR. Mutations in gyrA QRDR were found in 75.7% (156/206) of FQ(r) clinical isolates. Among those gyrA mutants, a majority (75.6%) harboured mutations at amino acid position 94, with D94G being the most frequent amino acid substitution. Mutations in gyrA QRDR showed 100% positive predictive value for FQ(r)M. tuberculosis in China. Mutations in gyrB were observed in 15.5% (32/206) of FQ(r) clinical isolates. Ten novel mutations were identified in gyrB. However, most of them also harboured mutations in gyrA, limiting their contribution to FQ(r) resistance in M. tuberculosis. Our findings indicated that, similar to other geographic regions, mutations in gyrA were shown to be the major mechanism of FQ(r) resistance in M. tuberculosis isolates. The mutations in gyrA QRDR can be a good molecular surrogate marker for detecting FQ(r)M. tuberculosis in China.