Genetic variation of Mycobacterium tuberculosis circulating in Kharkiv Oblast, Ukraine

<p>Abstract</p> <p>Background</p> <p>A persistent increase of tuberculosis cases has recently been noted in the Ukraine. The reported incidence of drug-resistant isolates of <it>M. tuberculosis </it>is growing steadily; however, data on the genetic variation of isolates of <it>M. tuberculosis </it>circulating in northern Ukraine and on the spectrum and frequency of occurrence of mutations determining resistance to the principal anti-tuberculosis drugs isoniazid and rifampicin have not yet been reported.</p> <p>Methods</p> <p>Isolates of <it>M. tuberculosis </it>from 98 tuberculosis patients living in Kharkiv Oblast (Ukraine) were analyzed using VNTR- and RFLP-IS6110-typing methods. Mutations associated with resistance to rifampicin and isoniazid were detected by RFLP-PCR methods, and also confirmed by sequencing.</p> <p>Results</p> <p>We identified 75 different genetic profiles. Thirty four (34%) isolates belonged to the Beijing genotype and 23 (23%) isolates belonged to the LAM family. A cluster of isolates belonging to the LAM family had significant genetic heterogeneity, indicating that this family had an ancient distribution and circulation in this geographical region. Moreover, we found a significant percentage of the isolates (36%) belonged to as yet unidentified families of <it>M. tuberculosis </it>or had individual non-clustering genotypes. Mutations conferring rifampicin and isoniazid resistance were detected in 49% and 54% isolates, respectively. Mutations in codon 531 of the <it>rpoB </it>gene and codon 315 of the <it>katG </it>gene were predominant among drug-resistant isolates. An association was found for belonging to the LAM strain family and having multiple drug resistance (R = 0.27, p = 0.0059) and also for the presence of a mutation in codon 531 of the <it>rpoB </it>gene and belonging to the Beijing strain family (R = 0.2, p = 0.04).</p> <p>Conclusions</p> <p>Transmission of drug-resistant isolates seems to contribute to the spread of resistant TB in this oblast. The Beijing genotype and LAM genotype should be seen as a major cause of drug resistant TB in this region.</p

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

Simplified treatment protocols improve recovery of children with severe acute malnutrition in South Sudan: results from a mixed methods study

Abstract Background As part of COVID-19 mitigation strategies, emergency nutrition program adaptations were implemented, but evidence of the effects is limited. Compared to the standard protocol, the full adapted protocol included adapted admissions criteria, simplified dosing, and reduced visit frequency; partially adapted protocols consisting of only some of these modifications were also implemented. To enable evidence-based nutrition program modifications as the context evolved, this study was conducted to characterize how protocol adaptations in South Sudan affected Outpatient Therapeutic Feeding Program outcomes. Methods A mixed methods approach consisting of secondary analysis of individual-level nutrition program data and key informant interviews was used. Analyses focused on program implementation and severe acute malnutrition treatment outcomes under the standard, full COVID-19 adapted, and partially adapted treatment protocols from 2019 through 2021. Analyses compared characteristics and outcomes by different admission types under the standard protocol and across four different treatment protocols. Regression models evaluated the odds of recovery and mean length of stay (LoS) under the four protocols. Results Very few (1.6%; n = 156) children admitted based on low weight-for-height alone under the standard protocol would not have been eligible for admission under the adapted protocol. Compared to the full standard protocol, the partially adapted (admission only) and partially adapted (admission and dosing) protocols had lower LoS of 28.4 days (CI − 30.2, − 26.5) and 5.1 days (CI − 6.2, − 4.0); the full adapted protocol had a decrease of 3.0 (CI − 5.1, − 1.0) days. All adapted protocols had significantly increased adjusted odds ratios (AOR) for recovery compared to the full standard protocol: partially adapted (admission only) AOR = 2.56 (CI 2.18–3.01); partially adapted (admission + dosing) AOR = 1.78 (CI 1.45–2.19); and fully adapted protocol AOR = 2.41 (CI 1.69–3.45). Conclusions This study provides evidence that few children were excluded when weight-for-height criteria were suspended. LoS was shortest when only MUAC was used for entry/exit but dosing and visit frequency were unchanged. Significantly shorter LoS with simplified dosing and visit frequency vs. under the standard protocol indicate that protocol adaptations may lead to shorter recovery and program enrollment times. Findings also suggest that good recovery is achievable with reduced visit frequency and simplified dosing

Comparison of hospital readmission after total hip and total knee arthroplasty vs spinal surgery after implementation of the hospital readmissions reduction program

Importance: The Hospital Readmissions Reduction Program (HRRP) was recently expanded to penalize excessive readmissions after total hip arthroplasty (THA) and total knee arthroplasty (TKA). These are the first surgical procedures to be included in the HRRP. Objective: To determine whether the HRRP was associated with a greater decrease in readmissions after targeted procedures (THA and TKA) compared with similar nontargeted procedures (lumbar spine fusion and laminectomy). Design, setting, and participants: A retrospective cohort study was conducted of patients 50 years or older among all payers in the Nationwide Readmissions Database who underwent THA, TKA, lumbar spine fusion, or laminectomy between January 1, 2010, and September 30, 2015. Multivariable logistic regression and interrupted time-series models were used to calculate and compare 30-day readmission trends in 3 periods associated with the HRRP: preimplementation (January 2010-September 2012), implementation (October 2012-September 2014), and penalty (October 2014-September 2015). Statistical analysis was performed from January 1, 2010, to September 30, 2015. Exposures: Announcement and implementation of the HRRP. Main outcomes and measures: Readmission within 30 days after hospitalization for THA, TKA, lumbar spine fusion, or laminectomy surgery. Results: The study included 6 687 077 (58.3% women and 41.7% men; mean age, 66.7 years; 95% CI, 66.7-66.8 years) weighted hospitalizations for THA, TKA, lumbar spine fusion, and laminectomy surgery: 4 765 466 hospitalizations for targeted conditions and 1 921 611 for nontargeted conditions. After passage of the Patient Protection and Affordable Care Act, the risk-adjusted rates of readmission after all procedures decreased in a similar fashion. Implementation of the HRRP was associated with a 0.018% per month decrease in the rate of readmission (95% CI, -0.025% to -0.010%) after targeted procedures, which was not observed after nontargeted procedures (slope per month, -0.003%; 95% CI, -0.016% to 0.010%). Penalties were not associated with a greater decrease in readmission for either targeted or nontargeted procedures. Conclusions and relevance: These results appear to be consistent with hospitals responding to the future possibility of penalties by reducing readmissions after surgical procedures targeted by the HRR

European genetic ancestry associated with risk of childhood ependymoma

BackgroundEpendymoma is a histologically defined central nervous system tumor most commonly occurring in childhood. Population-level incidence differences by race/ethnicity are observed, with individuals of European ancestry at highest risk. We aimed to determine whether extent of European genetic ancestry is associated with ependymoma risk in US populations.MethodsIn a multi-ethnic study of Californian children (327 cases, 1970 controls), we estimated the proportions of European, African, and Native American ancestry among recently admixed Hispanic and African American subjects and estimated European admixture among non-Hispanic white subjects using genome-wide data. We tested whether genome-wide ancestry differences were associated with ependymoma risk and performed admixture mapping to identify associations with local ancestry. We also evaluated race/ethnicity-stratified ependymoma incidence data from the Central Brain Tumor Registry of the United States (CBTRUS).ResultsCBTRUS data revealed that African American and Native American children have 33% and 36%, respectively, reduced incidence of ependymoma compared with non-Hispanic whites. In genetic analyses, a 20% increase in European ancestry was associated with a 1.31-fold higher odds of ependymoma among self-reported Hispanics and African Americans (95% CI: 1.08-1.59, Pmeta = 6.7 × 10-3). Additionally, eastern European ancestral substructure was associated with increased ependymoma risk in non-Hispanic whites (P = 0.030) and in Hispanics (P = 0.043). Admixture mapping revealed a peak at 20p13 associated with increased local European ancestry, and targeted fine-mapping identified a lead variant at rs6039499 near RSPO4 (odds ratio = 1.99; 95% CI: 1.45-2.73; P = 2.2 × 10-5) but which was not validated in an independent set of posterior fossa type A patients.ConclusionsInterethnic differences in ependymoma risk are recapitulated in the genomic ancestry of ependymoma patients, implicating regions to target in future association studies