Health care costs after total knee arthroplasty for satisfied and dissatisfied patients.

BACKGROUND: Evidence suggests that up to 21% of patients are dissatisfied after total knee arthroplasty (TKA), but the link between dissatisfaction and use of health care resources is unknown. The objective of this study was to compare costs after TKA between satisfied and dissatisfied patients. METHODS: This was a secondary analysis of a randomized clinical trial among patients who underwent primary TKA at our institution between 2015 and 2018. We estimated rates of satisfaction with pain relief and with return to function 1 year postoperatively. Patients prospectively reported use of health care resources 6 weeks, and 3, 6, 9 and 12 months after surgery. We compared costs between satisfied and dissatisfied patients from a public payer and a societal perspective. RESULTS: We included 156 patients in our analysis, of whom 42 (26.9%) were dissatisfied with pain, and 57 (36.5%) were dissatisfied with function. There was no significant difference in costs between patients dissatisfied with pain or function compared to satisfied patients from a health care payer perspective. From a societal perspective, patients dissatisfied with pain incurred a mean cost of $21 156.18, compared to $13 453.84 for satisfied patients (mean difference $7702.34, 95% confidence interval [CI] -89.43 to 15 494.11). Similarly, patients dissatisfied with function incurred a mean cost of $19 007.70, compared to $13 523.83 for those who were satisfied (mean difference $5483.87, 95% CI -526.34 to 11 494.10). CONCLUSION: Dissatisfied patients incurred greater costs than satisfied patients during the first year after TKA. The results justify further evaluation of factors contributing to patient satisfaction that may help to reduce the economic burden of TKA.

Exceptional origin activation revealed by comparative analysis in two laboratory yeast strains.

We performed a comparative analysis of replication origin activation by genome-wide single-stranded DNA mapping in two yeast strains challenged by hydroxyurea, an inhibitor of the ribonucleotide reductase. We gained understanding of the impact on origin activation by three factors: S-phase checkpoint control, DNA sequence polymorphisms, and relative positioning of origin and transcription unit. Wild type W303 showed a significant reduction of fork progression accompanied by an elevated level of Rad53 phosphorylation as well as physical presence at origins compared to A364a. Moreover, a rad53K227A mutant in W303 activated more origins, accompanied by global reduction of ssDNA across all origins, compared to A364a. Sequence polymorphism in the consensus motifs of origins plays a minor role in determining strain-specific activity. Finally, we identified a new class of origins only active in checkpoint-proficient cells, which we named "Rad53-dependent origins". Our study presents a comprehensive list of differentially used origins and provide new insights into the mechanisms of origin activation.

Health Economic Evaluations of Hip and Knee Interventions in Orthopaedic Sports Medicine: A Systematic Review and Quality Assessment.

BACKGROUND: The economic burden of musculoskeletal diseases is substantial and growing. Economic evaluations compare costs and health benefits of interventions simultaneously to help inform value-based care; thus, it is crucial to ensure that studies are using appropriate methodology to provide valid evidence on the cost-effectiveness of interventions. This is particularly the case in orthopaedic sports medicine, where several interventions of varying costs are available to treat common hip and knee conditions. PURPOSE: To summarize and evaluate the quality of economic evaluations in orthopaedic sports medicine for knee and hip interventions and identify areas for quality improvement. STUDY DESIGN: Systematic review; Level of evidence, 3. METHODS: The Medline, AMED, OVID Health Star, and EMBASE databases were searched from inception to March 1, 2020, to identify economic evaluations that compared ≥2 interventions for hip and/or knee conditions in orthopaedic sports medicine. We assessed the quality of full economic evaluations using the Quality of Health Economic Studies (QHES) tool, which consists of 16 questions for a total score of 100. We classified studies into quartiles based on QHES score (extremely poor quality to high quality) and we evaluated the frequency of studies that addressed each of the 16 QHES questions. RESULTS: A total of 93 studies were included in the systematic review. There were 41 (44%) cost analyses, of which 21 (51%) inappropriately concluded interventions were cost-effective. Only 52 (56%) of the included studies were full economic evaluations, although 40 of these (77%) fell in the high-quality quartile. The mean QHES score was 83.2 ± 19. Authors consistently addressed 12 of the QHES questions; questions that were missed or unclear were related to statistical uncertainty, appropriateness of costing methodology, and discussion of potential biases. The most frequently missed question was whether the cost perspective of the analysis was stated and justified. CONCLUSION: The number of studies in orthopaedic sports medicine is small, despite their overall good quality. Yet, there are still many highly cited studies based on low-quality or partial economic evaluations that are being used to influence clinical decision-making. Investigators should follow international health economic guidelines for study design and critical appraisal of studies to further improve quality.

Genome-wide mapping of DNA double-strand breaks from eukaryotic cell cultures using Break-seq.

We describe a genome-wide DNA double-strand break (DSB) mapping technique, Break-seq. In this protocol, we provide step-by-step instructions for cell embedment in agarose, in-gel DSB labeling and subsequent capture, followed by standard Illumina library construction and sequencing. We also provide the framework for sequence data processing and DSB peak identification. Finally, we present a custom-designed 3D-printed device for processing agarose-embedded DNA samples. The protocol is applicable to Saccharomyces cerevisiae, as well as mammalian suspension, adherent, and 3D organoid cell cultures. For complete details on the use and execution of this protocol, please refer to Hoffman et al. (2015) and Chakraborty et al. (2020).

Reactivation of super-enhancers by KLF4 in human Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a disease of significant morbidity and mortality and rarely diagnosed in early stages. Despite extensive genetic and genomic characterization, targeted therapeutics and diagnostic markers of HNSCC are lacking due to the inherent heterogeneity and complexity of the disease. Herein, we have generated the global histone mark based epigenomic and transcriptomic cartogram of SCC25, a representative cell type of mesenchymal HNSCC and its normal oral keratinocyte counterpart. Examination of genomic regions marked by differential chromatin states and associated with misregulated gene expression led us to identify SCC25 enriched regulatory sequences and transcription factors (TF) motifs. These findings were further strengthened by ATAC-seq based open chromatin and TF footprint analysis which unearthed Krüppel-like Factor 4 (KLF4) as a potential key regulator of the SCC25 cistrome. We reaffirm the results obtained from in silico and chromatin studies in SCC25 by ChIP-seq of KLF4 and identify ΔNp63 as a co-oncogenic driver of the cancer-specific gene expression milieu. Taken together, our results lead us to propose a model where elevated KLF4 levels sustains the oncogenic state of HNSCC by reactivating repressed chromatin domains at key downstream genes, often by targeting super-enhancers.

Molecular survey of basidiomycetes and divergence time estimation: An Indian perspective.

This study outlines the biodiversity of mushrooms of India. It reveals the molecular biodiversity and divergence time estimation of basidiomycetes from Gujarat, India. A total of 267 mushrooms were collected from 10 locations across the state. 225 ITS sequences were generated belonging to 105 species, 59 genera and 29 families. Phylogenetic analysis of Agaricaceae reveals monophyletic clade of Podaxis differentiating it from Coprinus. Further, the ancient nature of Podaxis supports the hypothesis that gasteroid forms evolved from secotioid forms. Members of Polyporaceae appeared polyphyletic. Further, our results of a close phylogenetic relationship between Trametes and Lenziteslead us to propose that the genera Trametes may by enlarged to include Lenzites. The tricholomatoid clade shows a clear demarcation for Entolomataceae. However, Lyophyllaceae and Tricholomataceae could not be distinguished clearly. Distribution studies of the mushrooms showed omnipresence of Ganoderma and Schizophyllum. Further, divergence time estimation shows that Dacrymycetes evolved in the Neoproterozoic Era and Hymenochaetales diverged from Agaricomycetes during the Silurian period.

A simple technique to reduce evaporation of crystallization droplets by using plate lids with apertures for adding liquids.

A method is described for using plate lids to reduce evaporation in low-volume vapor-diffusion crystallization experiments. The plate lids contain apertures through which the protein and precipitants were added to different crystallization microplates (the reservoir was filled before fitting the lids). Plate lids were designed for each of these commonly used crystallization microplates. This system minimizes the dehydration of crystallization droplets containing just a few nanolitres of protein and precipitant, and results in more reproducible diffraction from the crystals. For each lid design, changes in the weight of the plates were used to deduce the rate of evaporation under different conditions of temperature, air movement, droplet size and precipitant. For comparison, the state of dehydration was also visually assessed throughout the experiment. Finally, X-ray diffraction methods were used to compare the diffraction of protein crystals that were conventionally prepared against those that were prepared on plates with plate lids. The measurements revealed that the plate lids reduced the rate of evaporation by 63-82%. Crystals grown in 5 nl drops that were set up with plate lids diffracted to higher resolution than similar crystals from drops that were set up without plate lids. The results demonstrate that plate lids can be instrumental for improving few-nanolitre crystallizations.