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Abstract Background Globally, most people with multidrug-resistant tuberculosis (MDR-TB) and their households experience catastrophic costs of illness, diagnosis, and care. However, the factors associated with experiencing catastrophic costs are poorly understood. This study aimed to identify risk factors associated with catastrophic costs incurrence among MDR-TB-affected households in Ho Chi Minh City (HCMC), Viet Nam. Methods Between October 2020 and April 2022, data were collected using a locally-adapted, longitudinal WHO TB Patient Cost Survey in ten districts of HCMC. Ninety-four people with MDR-TB being treated with a nine-month TB regimen were surveyed at three time points: after two weeks of treatment initiation, completion of the intensive phase and the end of the treatment (approximately five and 10 months post-treatment initiation respectively). The catastrophic costs threshold was defined as total TB-related costs exceeding 20% of annual pre-TB household income. Logistic regression was used to identify variables associated with experiencing catastrophic costs. A sensitivity analysis examined the prevalence of catastrophic costs using alternative thresholds and cost estimation approaches. Results Most participants (81/93 [87%]) experienced catastrophic costs despite the majority 86/93 (93%) receiving economic support through existing social protection schemes. Among participant households experiencing and not experiencing catastrophic costs, median household income was similar before MDR-TB treatment. However, by the end of MDR-TB treatment, median household income was lower (258 [IQR: 0–516] USD vs. 656 [IQR: 462–989] USD; p = 0.003), and median income loss was higher (2838 [IQR: 1548–5418] USD vs. 301 [IQR: 0–824] USD; p

Abstract Background There is extensive evidence for the cost-effectiveness of programmatic and additional tuberculosis (TB) interventions, but no studies have employed the social return on investment (SROI) methodology. We conducted a SROI analysis to measure the benefits of a community health worker (CHW) model for active TB case finding and patient-centered care. Methods This mixed-method study took place alongside a TB intervention implemented in Ho Chi Minh City, Viet Nam, between October-2017 – September-2019. The valuation encompassed beneficiary, health system and societal perspectives over a 5-year time-horizon. We conducted a rapid literature review, two focus group discussions and 14 in-depth interviews to identify and validate pertinent stakeholders and material value drivers. We compiled quantitative data from the TB program’s and the intervention’s surveillance systems, ecological databases, scientific publications, project accounts and 11 beneficiary surveys. We mapped, quantified and monetized value drivers to derive a crude financial benefit, which was adjusted for four counterfactuals. We calculated a SROI based on the net present value (NPV) of benefits and investments using a discounted cash flow model with a discount rate of 3.5%. A scenario analysis assessed SROI at varying discount rates of 0-10%. Results The mathematical model yielded NPVs of US$235,511 in investments and US$8,497,183 in benefits. This suggested a return of US$36.08 for each dollar invested, ranging from US$31.66-US39.00 for varying discount rate scenarios. Conclusions The evaluated CHW-based TB intervention generated substantial individual and societal benefits. The SROI methodology may be an alternative for the economic evaluation of healthcare interventions.

Abstract Background The study purpose is to describe trajectories of financial distress for parents of children (ages 1–14.9 years) with newly diagnosed acute lymphoblastic leukemia (ALL). The secondary aim is to identify multilevel factors (child, parent, household, treating institution) that influence change in financial distress over time. Methods The study uses a prospective cohort design, repeated measurements, and mixed methods. The settings are Children’s Oncology Group (COG) institutions participating in the National Cancer Institute Community Oncology Research Program (NCORP). Eligible participants are English- and/or Spanish-speaking parents or legal guardians (hereafter “parents”) of index children. Parents are asked to complete a survey during their child’s induction (T1) and maintenance therapy (T2), and near treatment completion (T3). Study surveys include items about (a) the child’s cancer and clinical course, (b) parental socio-economic status, financial distress and financial coping behaviors, and (c) household material hardships. At least 15 parents will be invited to participate in an optional semi-structured interview. NCORP institutions that enroll at least one parent must complete an annual survey about institution resources that could influence parental financial distress. Discussion The results will inform future interventions to mitigate financial distress for parents of children diagnosed with ALL and could be instructive beyond this disease group. Trial registration This trial was initially registered with the NCI Clinical Trial Reporting Program ID: NCI-2021–03,567 on June 16, 2021. The study can be found on clinicaltrials.gov, Identifier NCT04928599 .

BackgroundChronic granulomatous disease (CGD) is an inborn error of immunity (IEI) disorder that results from defects in the respiratory burst activity in phagocytes, leading to the inability to kill bacterial and fungal microorganisms. CGD patients usually have a high incidence of morbidity such as infections and autoinflammatory diseases and a high mortality rate. Allogeneic bone marrow transplantation (BMT) is the only definitive cure for patients who suffer from CGD.Case presentationWe report the first transplant case of chronic granulomatous disease in Vietnam. A 25-month-old boy with X-linked CGD underwent bone marrow transplantation from his 5-year-old, full-matched human leukocyte antigen (HLA)-carrier sibling after myeloablative conditioning regimen with busulfan 5.1 mg/kg/day for 4 days, fludarabine 30 mg/m2/day for 5 days, and rATG (Grafalon-Fresenius) 10 mg/kg/day for 4 days. Neutrophil was engrafted on day 13 posttransplant, donor chimerism was 100% on day 30 with the dihydrorhodamine-1,2,3 (DHR 123) flow cytometric assay test that reached 38% of the normal 45 days posttransplant. Five months after transplant, the patient was free of infection with stable DHR 123 assay at 37%, and donor chimerism remained 100%. No sign of a graft-versus-host disease had been observed posttransplant.ConclusionWe suggest that bone marrow transplantation is a safe and effectual cure for CGD patients, especially for patients with HLA-identical siblings.

To achieve the Sustainable Development Goal's targets of universal health coverage (UHC) and poverty reduction, interventions are required that strengthen and harmonize both UHC and social protection. Vietnam is committed to achieving financial protection and over 90% of the general population has enrolled in its social health insurance (SHI) scheme. However, an estimated 63% of tuberculosis (TB)-affected households in Vietnam still face catastrophic costs and little is known about the optimal strategies to mitigate the costs of TB care for vulnerable families. This study assessed the acceptability of a social protection package containing cash transfers and SHI using individual interviews (n = 19) and focus group discussions (n = 3 groups). Interviews were analyzed through framework analysis. The study's main finding indicated that both conditional and unconditional cash transfers paired with SHI were acceptable, across six dimensions of acceptability. Cash transfers were considered beneficial for mitigating out-of-pocket expenditure, increasing TB treatment adherence, and improving mental health and general well-being, but the value provided was inadequate to fully alleviate the economic burden of the illness. The conditionality of the cash transfers was not viewed by participants as inappropriate, but it increased the workload of the TB program, which brought into question the feasibility of scale-up. SHI was viewed as a necessity by almost all participants, but people with TB questioned the quality of care received when utilizing it for auxiliary TB services. Access to multiple sources of social protection was deemed necessary to fully offset the costs of TB care. Additional research is needed to assess the impact of cash transfer interventions on health and economic outcomes in order to create an enabling policy environment for scale-up.

ObjectiveTo develop a summary format of clinical practice guideline (CPG) recommendations to improve understandability among health care professionals.MethodsWe developed a summary format based on current research and used the "Think Aloud" technique in one-on-one cognitive interviews to iteratively improve it. Interviews of health care professionals from Children's Oncology Group-member, National Cancer Institute Community Oncology Research Program sites were conducted. After every five interviews (a round), responses were reviewed, and changes made to the format until it was well understood and no new, substantive suggestions for revision were raised. We took a directed (deductive) approach to content analysis of the interview notes to identify concerns related to recommendation summary usability, understandability, validity, applicability and visual appeal.ResultsDuring seven rounds of interviews with 33 health care professionals, we identified important factors that influenced understandability. Participants found understanding weak recommendations more challenging than strong recommendations. Understanding was improved when the term 'conditional' recommendation was used instead of 'weak' recommendation. Participants found a Rationale section to be very helpful but desired more information when a recommendation entailed a practice change. In the final format, the recommendation strength is clearly indicated in the title, highlighted, and defined within a text box. The rationale for the recommendation is in a column on the left, with supporting evidence on the right. In a bulleted list, the Rationale section describes the benefits and harms and additional factors, such as implementation, that were considered by the CPG developers. Each bullet under the supporting evidence section indicates the level of evidence with an explanation and the supporting studies with hyperlinks when applicable.ConclusionsA summary format to present strong and conditional recommendations was created through an iterative interview process. The format is straightforward, making it easy for organizations and CPG developers to use it to communicate recommendations clearly to intended users.

Abstract Background Clinical practice guideline (CPG)-consistent care improves patient outcomes, but CPG implementation is poor. Little is known about CPG implementation in pediatric oncology. This study aimed to understand supportive care CPG implementation facilitators and barriers at pediatric oncology National Cancer Institute (NCI) Community Oncology Research Program (NCORP) institutions. Methods Healthcare professionals at 26 pediatric, Children's Oncology Group-member, NCORP institutions were invited to participate in face-to-face focus groups. Serial focus groups were held until saturation of ideas was reached. Supportive care CPG implementation facilitators and barriers were solicited using nominal group technique (NGT), and implementation of specific supportive care CPG recommendations was discussed. Notes from each focus group were analyzed using a directed content analysis. The top five themes arising from an analysis of NGT items were identified, first from each focus group and then across all focus groups. Results Saturation of ideas was reached after seven focus groups involving 35 participants from 18 institutions. The top five facilitators of CPG implementation identified across all focus groups were organizational factors including charging teams with CPG implementation, individual factors including willingness to standardize care, user needs and values including mentorship, system factors including implementation structure, and implementation strategies including a basis in science. The top five barriers of CPG implementation identified were organizational factors including tolerance for inconsistencies, individual factors including lack of trust, system factors including administrative hurdles, user needs and values including lack of inclusivity, and professional including knowledge gaps. Conclusions Healthcare professionals at pediatric NCORP institutions believe that organizational factors are the most important determinants of supportive care CPG implementation. They believe that CPG-consistent supportive care is most likely to be delivered in organizations that prioritize evidence-based care, provide structure and resources to implement CPGs, and eliminate implementation barriers. Trial registration ClinicalTrials.gov Identifier: NCT02847130. Date of registration: July 28, 2016.

The purpose of this work is to evaluate the performance of novel hydrfo-pneumatic suspension system (HPSs) in comparison with traditional hydro-pneumatic fsuspension system (HPSs) of a heavy truck in the direction of improving vehicle ride comfort. Firstly, the nonlinear dynamic models of the traditional and novel HPS systems are set up to determine the vertical forces. And then, the vertical forces are connected with a 3-D nonlinear dynamic model of heavy truck with 10 degrees of freedom under random excitation of road surface. The root mean square (RMS) acceleration responses of the vertical cab, pitch and roll angles of the cab (awzcb, awfcb and awtcb) based on the International Standard ISO 2631-1: 1997 are chosen as objective functions. The study results show that the awzcb, awfcb and awtcb values with novel HPSs reduce by 28.27%, 28.32% and 6.89% in comparison with traditional HPSs when vehicle moves on ISO class D road surface at vehicle speed of 50 km/h and full load. Finally, the ride performance of novel HPSs is verified and compared and evaluated with traditional HPSs under different operating conditions and the evaluation results are also indicated that the ride performance of a novel HPSs is better than the traditional HPSs under survey conditions.

The construction machinery market has required increasingly not only on working capacity but also ride comfort quality, therefore it has required increasing toward researchers and manufacturers. The main objective of this paper proposes and evaluates the performance of semi-active hydraulic cab mount system (SHCMs) of a double-drum vibratory roller in the direction of enhancing vehicle ride comfort under different operating conditions. Firstly, a nonlinear dynamic model of passive hydraulic cab mount system (PHCMs) is established to determine its vertical force which is connected with a dynamic model of vehicle - ground surface interaction. And then, a fuzzy logic controller (FLC) is designed to control the value of the damping force of SHCMs. Both the differential equations of motion and FLC are implemented in the MATLAB/Simulink environment. Finally, the ride performance of SHCMs is evaluated under different conditions according to ISO 2631: 1997 (E) standard. The obtained results show that the values of objective functions with SHCMs significantly reduce in comparison with PHCMs under different operating conditions.

Across Asia, a large proportion of people with tuberculosis (TB) do not report symptoms, have mild symptoms or only experience symptoms for a short duration. These individuals may not seek care at health facilities or may be missed by symptom screening, resulting in sustained TB transmission in the community. We evaluated the yields of TB from 114 days of community-based, mobile chest X-ray (CXR) screening. The yields at each step of the TB screening cascade were tabulated and we compared cohorts of participants who reported having a prolonged cough and those reporting no cough or one of short duration. We estimated the marginal yields of TB using different diagnostic algorithms and calculated the relative diagnostic costs and cost per case for each algorithm. A total of 34,529 participants were screened by CXR, detecting 256 people with Xpert-positive TB. Only 50% of those diagnosed with TB were detected among participants reporting a prolonged cough. The study’s screening algorithm detected almost 4 times as much TB as the National TB Program’s standard diagnostic algorithm. Community-based, mobile chest X-ray screening can be a high yielding strategy which is able to identify people with TB who would likely otherwise have been missed by existing health services.

Thermodynamic properties and anharmonic effects in X-ray absorption fine structure (XAFS) have been studied based on the anharmonic correlated Debye model Debye–Waller factors presented in terms of cumulant expansion. The derived analytical expressions of three first XAFS cumulants involve more information on phonon-phonon interactions taken from integration over the first Brillouin zone. Many-body effects are taken into account in the present one-dimensional model based on the first shell near neighbor contributions to the vibrations between absorber and backscatterer atoms. Morse potential is assumed to describe single-pair atomic interaction included in the derived anharmonic interatomic effective potential. The present theory can be applied to any crystal structure including complex systems. Numerical results for Cu and Ni are found to be in good agreement with experiment and with those of the other theories.

Tuberculosis (TB) causes more deaths worldwide than any other infectious disease. Progress in reducing the global burden of TB stalled during the COVID-19 pandemic; an estimated 10.6 million persons became [...]

Alternaria alternata produces more than 60 secondary metabolites, among which alternariol (AOH) and alternariol-9-methyl ether (AME) are important mycotoxins. Whereas the toxicology of these two polyketide-based compounds has been studied, nothing is known about the genetics of their biosynthesis. One of the postulated core enzymes in the biosynthesis of AOH and AME is polyketide synthase (PKS). In a draft genome sequence of A. alternata we identified 10 putative PKS-encoding genes. The timing of the expression of two PKS genes, pksJ and pksH, correlated with the production of AOH and AME. The PksJ and PksH proteins are predicted to be 2222 and 2821 amino acids in length, respectively. They are both iterative type I reducing polyketide synthases. PksJ harbors a peroxisomal targeting sequence at the C-terminus, suggesting that the biosynthesis occurs at least partly in these organelles. In the vicinity of pksJ we found a transcriptional regulator, altR, involved in pksJ induction and a putative methyl transferase, possibly responsible for AME formation. Downregulation of pksJ and altR caused a large decrease of alternariol formation, suggesting that PksJ is the polyketide synthase required for the postulated Claisen condensations during the biosynthesis. No other enzymes appeared to be required. PksH downregulation affected pksJ expression and thus caused an indirect effect on AOH production.

Abstract Background Tuberculosis (TB) in children is rarely confirmed due to the lack of effective diagnostic tools; only 10 to 15% of pediatric TB is smear positive due to paucibacillary samples and the difficulty of obtaining high-quality specimens from children. We evaluate here the accuracy of Xpert MTB/RIF in comparison with the Micoroscopic observation drug susceptibility (MODS) assay for diagnosis of TB in children using samples stored during a previously reported evaluation of the MODS assay. Methods Ninety-six eligible children presenting with suspected TB were recruited consecutively at Pham Ngoc Thach Hospital in Ho Chi Minh City Viet Nam between May to December 2008 and tested by Ziehl-Neelsen smear, MODS and Mycobacterial growth Indicator (MGIT, Becton Dickinson) culture. All samples sent by the treating clinician for testing were included in the analysis. An aliquot of processed sample deposit was stored at −20°C and tested in the present study by Xpert MTB/RIF test. 183 samples from 73 children were available for analysis by Xpert. Accuracy measures of MODS and Xpert were summarized. Results The sensitivity (%) in detecting children with a clinical diagnosis of TB for smear, MODS and Xpert were 37.9 [95% CI 25.5; 51.6], 51.7 [38.2; 65.0] and 50.0 [36.6; 63.4], respectively (per patient analysis). Xpert was significantly more sensitive than smear (P=0.046). Testing of additional samples did not increase case detection for MODS while testing of a second sputum sample by Xpert detected only two additional cases. The positive and negative predictive values (%) of Xpert were 100.0 [88.0; 100.0] and 34.1 [20.5; 49.9], respectively, while those of MODS were 96.8 [83.3; 99.9] and 33.3 [19.6; 49.5]. Conclusion MODS culture and Xpert MTB/RIF test have similar sensitivities for the detection of pediatric TB. Xpert MTB RIF is able to detect tuberculosis and rifampicin resistance within two hours. MODS allows isolation of cultures for further drug susceptibility testing but requires approximately one week to become positive. Testing of multiple samples by xpert detected only two additional cases and the benefits must be considered against costs in each setting. Further research is required to evaluate the optimal integration of Xpert into pediatric testing algorithms.

The study aims to synthesize nano CeO2 and Pr2O3 materials to use as fertilizer for cultivation of the Salvia miltiorrhiza Bunge, which is also known as Danshen, an important medicinal plant in many Asian countries. The extraction experiments were also conducted to determine tanshinone IIA contents in the Danshen root to acutely explore effects of the nano‐materials on accumulation of valuable medicine in the plant. The obtained results indicated that nano CeO2 and Pr2O3 applications significantly induced both growth and tanshinone IIA contents of the Danshen. Firstly, the CeO2 application greatly induced side branch and root development of the Danshen rather than the height of the plant, while the Pr2O3 application greatly induced plant height and root growth of the Danshen rather than side branch development. In comparison, the CeO2 effectively induced root growth and tanshinone IIA content in the Danshen rather than the Pr2O3 did. Finally, simultaneous applications of nano Pr2O3 and CeO2 revealed synergic effects to greatly promote the growth of the Danshen. The tanshinone IIA content extracted from the roots of the mixture Pr2O3 and CeO2 exposed Danshen was approximately 0.4318 %, which was higher than those of single CeO2 and Pr2O3 exposed plants. [ABSTRACT FROM AUTHOR]

Background Tuberculous meningitis (TBM) is difficult to diagnose. We investigated whether a 3-gene host response signature in blood can distinguish TBM from other brain infections. Methods The expression of 3 genes (dual specificity phosphatase 3 [ DUSP3 ], guanylate-binding protein [ GBP5 ], krupple-like factor 2 [ KLF2 ]) was analyzed by RNA sequencing of archived whole blood from 4 cohorts of Vietnamese adults: 281 with TBM, 279 with pulmonary tuberculosis, 50 with other brain infections, and 30 healthy controls. Tuberculosis scores (combined 3-gene expression) were calculated following published methodology and discriminatory performance compared using area under a receiver operator characteristic curve (AUC). Results GBP5 was upregulated in TBM compared to other brain infections (P <.001), with no difference in DUSP3 and KLF2 expression. The diagnostic performance of GBP5 alone (AUC, 0.74; 95% confidence interval [CI],.67–.81) was slightly better than the 3-gene tuberculosis score (AUC, 0.66; 95% CI,.58–.73) in TBM. Both GBP5 expression and tuberculosis score were higher in participants with human immunodeficiency virus (HIV; P <.001), with good diagnostic performance of GBP5 alone (AUC, 0.86; 95% CI,.80–.93). Conclusions The 3-gene host signature in whole blood has the ability to discriminate TBM from other brain infections, including in individuals with HIV. Validation in large prospective diagnostic study is now required. [ABSTRACT FROM AUTHOR]