Tuberculosis transmission continues to be a major public health challenge. In this cluster-randomized, controlled trial conducted in Vietnam, active community-wide screening for tuberculosis over 4 ...years is shown to decrease the prevalence of tuberculosis.
Polysaccharide monooxygenases (PMOs) use a type-2 copper center to activate O2 for the selective hydroxylation of one of the two C–H bonds of glycosidic linkages. Our electron paramagnetic resonance ...(EPR) analysis and molecular dynamics (MD) simulations suggest the unprecedented dynamic roles of the loop containing the residue G89 (G89 loop) on the active site structure and reaction cycle of starch-active PMOs (AA13 PMOs). In the Cu(II) state, the G89 loop could switch between an “open” and “closed” conformation, which is associated with the binding and dissociation of an aqueous ligand in the distal site, respectively. The conformation of the G89 loop influences the positioning of the copper center on the preferred substrate of AA13 PMOs. The dissociation of the distal ligand results in the bending of the T-shaped core of the Cu(II) active site, which could help facilitate its reduction to the active Cu(I) state. In the Cu(I) state, the G89 loop is in the “closed” conformation with a confined copper center, which could allow for efficient O2 binding. In addition, the G89 loop remains in the “closed” conformation in the Cu(II)-superoxo intermediate, which could prevent off-pathway superoxide release via exchange with the distal aqueous ligand. Finally, at the end of the reaction cycle, aqueous ligand binding to the distal site could switch the G89 loop to the “open” conformation and facilitate product release.
Background and objective
Data on the prevalence of anti-tuberculous drug resistance and its association with genetic mutations in
Mycobacterium tuberculosis
are limited. Our study explores the ...genomics of tuberculosis in Ca Mau, Vietnam.
Methods
Patients ≥15 years in Ca Mau Province, Vietnam, were screened annually for tuberculosis between 2014 and 2017. Isolates underwent drug susceptibility testing (DST) using the breakpoint method. DNA was extracted and whole genome sequencing (WGS) was performed.
Results
We identified 365 positive sputum cultures for
M. tuberculosis
and processed 237 for DST and 265 for WGS. Resistance to isoniazid was present in 19.8% (95% CI 14.7 to 24.9%), rifampicin in 3.5% (1.1 to 5.7%) and ethambutol in 2.5% (0.9 to 5.4%) of isolates. Relevant mutations in
rpoB
gene were detected in 3.8% (1.8 to 6.8%).
katG, inhA
or
fabG1
mutations were found in 19.6% (15.0 to 24.9%) with
KatG
being most common at 12.8% (9.1–17.5%). We found 38.4% of isolates were of Beijing lineage, 49.4% East-African-Indian lineage and 8.4% European-American lineage. There were no associations between resistance profiles and clinical features.
Conclusion
The high burden of isoniazid resistance and the
katG
mutation highlights the challenges facing Vietnam in its efforts to achieve its EndTB goals.
Abstract
Most of the existing chest X-ray datasets include labels from a list of findings without specifying their locations on the radiographs. This limits the development of machine learning ...algorithms for the detection and localization of chest abnormalities. In this work, we describe a dataset of more than 100,000 chest X-ray scans that were retrospectively collected from two major hospitals in Vietnam. Out of this raw data, we release 18,000 images that were manually annotated by a total of 17 experienced radiologists with 22 local labels of rectangles surrounding abnormalities and 6 global labels of suspected diseases. The released dataset is divided into a training set of 15,000 and a test set of 3,000. Each scan in the training set was independently labeled by 3 radiologists, while each scan in the test set was labeled by the consensus of 5 radiologists. We designed and built a labeling platform for DICOM images to facilitate these annotation procedures. All images are made publicly available in DICOM format along with the labels of both the training set and the test set.
Tuberculosis continues to be a major public health challenge worldwide. Investigators in Vietnam found that a community-wide case-finding program reduced the incidence of new tuberculosis cases over ...a 4-year period.
Display omitted
We report herein a method for the synthesis of 1-arylsulfonyl pyrrolo1,2-aquinoxalines. The process included electrophilic iodination with N-iodosuccinimide of ...pyrrolo1,2-aquinoxalines and a copper-catalyzed sulfonylation with sodium aryl sulfinates. An array of functionalities including ester, nitro, and ketone groups are tolerated under reaction conditions. Two possibilities to rationalize the mechanism for sulfonylation are considered.
Abstract
Background
Long-acting injectable (LAI) antipsychotics, along with community treatment orders (CTOs), are used to improve treatment effectiveness through adherence among individuals with ...schizophrenia. Understanding real-world medication adherence, and healthcare resource utilization (HRU) and costs in individuals with schizophrenia overall and by CTO status before and after second generation antipsychotic (SGA)-LAI initiation may guide strategies to optimize treatment among those with schizophrenia.
Methods
This retrospective observational single-arm study utilized administrative health data from Alberta, Canada. Adults (≥ 18 years) with schizophrenia who initiated a SGA-LAI (no use in the previous 2-years) between April 1, 2014 and March 31, 2016, and had ≥ 1 additional dispensation of a SGA-LAI were included; index date was the date of SGA-LAI initiation. Medication possession ratio (MPR) was determined, and paired t-tests were used to examine mean differences in all-cause and mental health-related HRU and costs (Canadian dollars), comprised of hospitalizations, physician visits, emergency department visits, and total visits, over the 2-year post-index and 2-year pre-index periods. Analyses were stratified by presence or absence of an active CTO during the pre-index and/or post-index periods.
Results
Among 1,211 adults with schizophrenia who initiated SGA-LAIs, 64% were males with a mean age of 38 (standard deviation SD 14) years. The mean overall antipsychotic MPR was 0.39 (95% confidence interval CI 0.36, 0.41) greater during the 2-year post-index period (0.84 SD 0.26) compared with the 2-year pre-index period (0.45 SD 0.40). All-cause and mental health-related HRU and costs were lower post-index versus pre-index (
p
< 0.001) for hospitalizations, physician visits, emergency department visits, and total visits; mean total all-cause HRU costs were $33,788 (95% CI -$38,993, -$28,583) lower post- versus pre-index ($40,343 SD $68,887 versus $74,131 SD $75,941), and total mental health-related HRU costs were $34,198 (95%CI -$39,098, -$29,297) lower post- versus pre-index ($34,205 SD $63,428 versus $68,403 SD $72,088) per-patient. Forty-three percent had ≥ 1 active CTO during the study period; HRU and costs varied according to CTO status.
Conclusions
SGA-LAIs are associated with greater medication adherence, and lower HRU and costs however the latter vary according to CTO status.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Background Community-wide screening for tuberculosis with Xpert MTB/RIF as a primary screening tool overcomes some of the limitations of conventional screening. However, concerns exist about ...the low positive predictive value of this test in screening settings. We did a cross-sectional assessment of this diagnostic test to directly estimate the actual positive predictive value of Xpert MTB/RIF when used in the setting of community-wide screening for tuberculosis, and to draw an inference about the specificity of the test for tuberculosis detection. Methods Field staff visited households in 60 randomly selected villages in Ca Mau province, Vietnam. We included people aged 15 years or older who provided written informed consent and were able to produce 0·5 mL or more of sputum, irrespective of reported symptoms. Participants were tested with Xpert MTB/RIF, then those with positive results had two further sputum samples tested for smear microscopy and culture, and underwent chest radiography at the provincial TB Health Center. The positive predictive value of Xpert MTB/RIF was compared against two reference standards for tuberculosis diagnosis—a positive sputum culture for Mycobacterium tuberculosis , and a positive sputum culture or a chest radiograph consistent with active pulmonary tuberculosis. We then calculated the specificity of Xpert MTB/RIF for tuberculosis detection on the basis of these positive predictive values and disease prevalence in this setting. Findings 43 435 adults consented to screening with Xpert MTB/RIF. Sputum samples of 0·5 mL or greater were collected from 23 202 participants, producing 22 673 valid results. 169 participants had positive Xpert MTB/RIF results (0·39% of those screened and 0·75% of those with valid sputum results). The positive predictive value of Xpert MTB/RIF was 61·0% (95% CI 52·8–68·7) when compared against a positive sputum culture and 83·9% (76·8–89·2) when compared against a positive sputum culture or chest radiograph consistent with active tuberculosis. On the basis of these positive predictive values, the specificity of Xpert MTB/RIF was determined to be between 99·78% (95% CI 99·71–99·84) and 99·93% (99·88–99·96). Interpretation The positive predictive value and specificity of Xpert MTB/RIF in the context of community-wide screening for tuberculosis is substantially higher than that predicted in previous studies. Our findings support the potential role of Xpert MTB/RIF as a primary screening tool to detect prevalent cases of tuberculosis in the community. Funding Australian National Health and Medical Research Council.
Abstract
Objective
Understand health resource, medication use, and cost of adults with chronic migraine who received guideline‐recommended onabotulinumtoxinA (botulinum toxin) treatment frequency and ...then continued or reduced/stopped.
Background
Botulinum toxin may be a beneficial treatment for chronic migraine; the trajectory of health resources utilization among those with continued or reduced/stopped use is unclear.
Methods
A retrospective population‐based cohort study utilizing administrative data from Alberta, Canada (2012–2020), was performed. A cohort of adults who received ≥5 botulinum toxin treatment cycles for chronic migraine over 18 months (6‐month run‐in; 1‐year pre‐index period) were grouped into those who (1) continued use (≥3 treatments/year), or (2) stopped or reduced use (stopped for 6 months then received 0 or 1–2 treatments/year, respectively) over a 1‐year post‐index period. Health resources and medication use were described, and pre–post costs were assessed. A second cohort that received ≥3 treatments/year immediately followed by 1 year of stopped or reduced use was considered in sensitivity analysis.
Results
Pre–post health resource, medication use, and costs were similar among those with continued use (
n
= 3336). Among those who stopped or reduced use (
n
= 1099; 756 stopped, 343 reduced), health resource, medication use, and costs were lower in the post‐ (total median per‐person cost IQR: all‐cause $4851 $8090; migraine‐related $835 $1915) versus pre‐ (all‐cause $6096 $7207; migraine‐related $2995 $1950) index period (estimated cost ratios 95% CI: total all‐cause 0.86 0.79, 0.95; total migraine‐related 0.44 0.40, 0.48). In the second cohort (
n
= 3763), return to continued use (≥3 treatments/year) occurred in up to 70.4% in those with reduced use.
Conclusions
Of adults treated with botulinum toxin for chronic migraine, 75.2% had continued use, stable health resource and medication use, and costs over a 2 year period. In those that stopped/reduced use, the observed lower health resource and migraine medication use may indicate improved symptom control, but the resumption of guideline‐recommended treatment intervals after reduced use was common.
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