MXene-Decorated Nanofibrous Membrane with Programmed Antibacterial and Anti-Inflammatory Effects via Steering NF-κB Pathway for Infectious Cutaneous Regeneration.

Although antibiotic is still the main choice for antibacteria both in hospital and community, phototherapy has become a possibly one of the alternative approaches in the treatment of microbe-associated infections nowadays because of its considerable potential in effective eradication of pathogenic bacteria. However, overwhelming reactive oxygen species (ROS) generated from phototherapy inevitably provoke an inflammatory response, complicating the healing process. To address this outstanding issue, a MXene-decorated nanofibrious is devised that not only yield localized heat but also elevate ROS levels under near-infrared laser exposure ascribed to the synergistic photothermal/photodynamic effect, for potent bacterial inactivation. After being further loaded with aspirin, the nanofibrous membranes exhibit benign cytocompatibility, boosting cell growth and suppressing the (nuclear factor kappa-B ( NF-κB) signaling pathways through RNA sequencing analysis, indicating an excellent anti-inflammatory effect. Interestingly, in vivo investigations also corroborate that the nanofibrous membranes accelerate infectious cutaneous regeneration by efficiently killing pathogenic bacteria, promoting collagen deposition, boosting angiogenesis, and dampening inflammatory reaction via steering NF-κB pathway. As envisaged, this work furnishes a decorated nanofibrous membrane with programmed antibacterial and anti-inflammatory effects for remedy of refractory bacteria-invaded wound regeneration.

Altering phosphorylation in cancer through PP2A modifiers.

Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase integral to the regulation of many cellular processes. Due to the deregulation of PP2A in cancer, many of these processes are turned toward promoting tumor progression. Considerable research has been undertaken to discover molecules capable of modulating PP2A activity in cancer. Because PP2A is capable of immense substrate specificity across many cellular processes, the therapeutic targeting of PP2A in cancer can be completed through either enzyme inhibitors or activators. PP2A modulators likewise tend to be effective in drug-resistant cancers and work synergistically with other known cancer therapeutics. In this review, we will discuss the patterns of PP2A deregulation in cancer, and its known downstream signaling pathways important for cancer regulation, along with many activators and inhibitors of PP2A known to inhibit cancer progression.

Engineered Bio-Heterojunction with Infection-Primed H2 S Liberation for Boosted Angiogenesis and Infectious Cutaneous Regeneration.

Photodynamic therapy (PDT) acts as a powerful weapon against infectious diseases for its enormous antimicrobial activity that quickly elicits storms of reactive oxygen species (ROS). Nevertheless, redundant ROS during treatment inevitably bring detriments in revascularization. To address this dilemma, an innovative P-N bio-heterojunction (bio-HJ) material consisting of p-type copper sulfide (p-CuS), n-type bismuth sulfide (n-Bi2 S3 ), and lactate oxidase (LOx) for effective treatment of recalcitrant infectious wounds by promoting angiogenesis is devised. LOx exhausts lactic acid accumulated in infection environment and converts it to hydrogen peroxide (H2 O2 ), which subsequently yields bactericidal hydroxyl radicals (·OH) via Fenton-like reactions. Ultimately, the P-N bio-HJs exert synergistic photothermal, photodynamic, and chemodynamic effects for rapid bacterial annihilation. Moreover, in vitro and RNA-seq analyses reveal that the crafted bio-HJs dramatically expedite the proliferation of L929 cells and promote angiogenesis by up-regulating angiogenic gene expression in hypoxia-inducible factor-1 (HIF-1) signaling pathway, which may ascribe to the evolution of H2 S in response to the infection microenvironment. Critically, results of in vivo experiments have authenticated that the bio-HJs significantly boost healing rates of full-thickness wounds by slaughtering bacteria, elevating angiogenesis, and promoting cytothesis. As envisioned, this work furnishes a novel tactic for the effective treatment of bacteria-invaded wound using H2 S-liberating P-N bio-HJs.

Multiple Respiratory Syncytial Virus (RSV) Strains Infecting HEp-2 and A549 Cells Reveal Cell Line-Dependent Differences in Resistance to RSV Infection.

Respiratory syncytial virus (RSV) is a leading cause of pediatric acute respiratory infection worldwide. There are currently no approved vaccines or antivirals to combat RSV disease. A few transformed cell lines and two historic strains have been extensively used to study RSV. Here, we reported a thorough molecular and cell biological characterization of HEp-2 and A549 cells infected with one of four strains of RSV representing both major subgroups as well as historic and more contemporary genotypes (RSV/A/Tracy [GA1], RSV/A/Ontario [ON], RSV/B/18537 [GB1], and RSV/B/Buenos Aires [BA]) via measurements of viral replication kinetics and viral gene expression, immunofluorescence-based imaging of gross cellular morphology and cell-associated RSV, and measurements of host response, including transcriptional changes and levels of secreted cytokines and growth factors. IMPORTANCE Infection with the respiratory syncytial virus (RSV) early in life is essentially guaranteed and can lead to severe disease. Most RSV studies have involved either of two historic RSV/A strains infecting one of two cell lines, HEp-2 or A549 cells. However, RSV contains ample variation within two evolving subgroups (A and B), and HEp-2 and A549 cell lines are genetically distinct. Here, we measured viral action and host response in both HEp-2 and A549 cells infected with four RSV strains from both subgroups and representing both historic and more contemporary strains. We discovered a subgroup-dependent difference in viral gene expression and found A549 cells were more potently antiviral and more sensitive, albeit subtly, to viral variation. Our findings revealed important differences between RSV subgroups and two widely used cell lines and provided baseline data for experiments with model systems better representative of natural RSV infection.

Tyrosine's Unique Role in the Hierarchical Assembly of Recombinant Spider Silk Proteins: From Spinning Dope to Fibers.

Producing recombinant spider silk fibers that exhibit mechanical properties approaching native spider silk is highly dependent on the constitution of the spinning dope. Previously published work has shown that recombinant spider silk fibers spun from dopes with phosphate-induced pre-assembly (biomimetic dopes) display a toughness approaching native spider silks far exceeding the mechanical properties of fibers spun from dopes without pre-assembly (classical dopes). Dynamic light scattering experiments comparing the two dopes reveal that biomimetic dope displays a systematic increase in assembly size over time, while light microscopy indicates liquid-liquid-phase separation (LLPS) as evidenced by the formation of micron-scale liquid droplets. Solution nuclear magnetic resonance (NMR) shows that the structural state in classical and biomimetic dopes displays a general random coil conformation in both cases; however, some subtle but distinct differences are observed, including a more ordered state for the biomimetic dope and small chemical shift perturbations indicating differences in hydrogen bonding of the protein in the different dopes with notable changes occurring for Tyr residues. Solid-state NMR demonstrates that the final wet-spun fibers from the two dopes display no structural differences of the poly(Ala) stretches, but biomimetic fibers display a significant difference in Tyr ring packing in non-ß-sheet, disordered helical domains that can be traced back to differences in dope preparations. It is concluded that phosphate pre-orders the recombinant silk protein in biomimetic dopes resulting in LLPS and fibers that exhibit vastly improved toughness that could be due to aromatic ring packing differences in non-ß-sheet domains that contain Tyr.

Impact of selenium nanoparticles in the regulation of inflammation.

The ability to develop novel medications based on nanoscale complexes has greatly enhanced the capabilities of current pharmaceuticals and has made multidimensional research of these complexes extremely relevant in recent years. Selenium nanoparticles (SeNPs) constitute one such example which in general, could be created by biological, chemical, and physical techniques. Biogenic SeNPs show improved compatibility with human organs and tissues. While sufficient levels of selenium (Se) are crucial for triggering immunity, they also play a role in controlling exaggerated immunological responses and persistent inflammation. More significantly, SeNPs can activate the immune systems, both innate and adaptive, in the tumor microenvironment, which results in an immunological response that fights various diseases caused by chronic inflammation. In this article, we discuss the functions of Se and SeNPs in controlling inflammation with particular emphasis given to their role in combating inflammation in different diseases. Finally, even though Se status exhibits considerable promise as a reliable indicator of autoimmune and inflammatory diseases, novel functionalized SeNPs may likely offer a more effective and reliable tool in both disease prevention and treatment.

Receipt of Tobacco Treatment and One-Year Smoking Cessation Rates Following Lung Cancer Screening in the Veterans Health Administration.

BACKGROUND: Implementation of effective smoking cessation interventions in lung cancer screening has been identified as a high-priority research gap, but knowledge of current practices to guide process improvement is limited due to the slow uptake of screening and dearth of data to assess cessation-related practices and outcomes under real-world conditions. OBJECTIVE: To evaluate cessation treatment receipt and 1-year post-screening cessation outcomes within the largest integrated healthcare system in the USA-the Veterans Health Administration (VHA). Design Observational study using administrative data from electronic medical records (EMR). Patients Currently smoking Veterans who received a first lung cancer screening test using low-dose CT (LDCT) between January 2014 and June 2018. Main Outcomes Tobacco treatment received within the window of 30 days before and 30 days after LDCT; 1-year quit rates based on EMR Smoking Health Factors data 6-18 months after LDCT. Key Results Of the 47,609 current smokers screened (95.3% male), 8702 (18.3%) received pharmacotherapy and/or behavioral treatment for smoking cessation; 531 (1.1%) received both. Of those receiving pharmacotherapy, only one in four received one of the most effective medications: varenicline (12.1%) or combination nicotine replacement therapy (14.3%). Overall, 5400 Veterans quit smoking-a rate of 11.3% (missing=smoking) or 13.5% (complete case analysis). Treatment receipt and cessation were associated with numerous sociodemographic, clinical, and screening-related factors. CONCLUSIONS: One-year quit rates for Veterans receiving lung cancer screening in VHA are similar to those reported in LDCT clinical trials and cohort studies (i.e., 10-17%). Only 1% of Veterans received the recommended combination of pharmacotherapy and counseling, and the most effective pharmacotherapies were not the most commonly received ones. The value of screening within VHA could be improved by addressing these treatment gaps, as well as the observed disparities in treatment receipt or cessation by race, rurality, and psychiatric conditions.

Outcomes from a mechanistic biomarker multi-arm and randomised study of liposomal MTP-PE (Mifamurtide) in metastatic and/or recurrent osteosarcoma (EuroSarc-Memos trial).

The phase III clinical study of adjuvant liposomal muramyl tripeptide (MTP-PE) in resected high-grade osteosarcoma (OS) documented positive results that have been translated into regulatory approval, supporting initial promise for innate immune therapies in OS. There remains, however, no new approved treatment such as MTP-PE for either metastatic or recurrent OS. Whilst the addition of different agents, including liposomal MTP-PE, to surgery for metastatic or recurrent high-grade osteosarcoma has tried to improve response rates, a mechanistic hiatus exists in terms of a detailed understanding the therapeutic strategies required in advanced disease. Here we report a Bayesian designed multi-arm, multi-centre, open-label phase II study with randomisation in patients with metastatic and/or recurrent OS, designed to investigate how patients with OS might respond to liposomal MTP-PE, either given alone or in combination with ifosfamide. Despite the trial closing because of poor recruitment within the allocated funding period, with no objective responses in eight patients, we report the design and feasibility outcomes for patients registered into the trial. We demonstrate the feasibility of the Bayesian design, European collaboration, tissue collection with genomic analysis and serum cytokine characterisation. Further mechanistic investigation of liposomal MTP-PE alone and in combination with other agents remains warranted in metastatic OS.

Experiences of racism and postpartum depression symptoms, care-seeking, and diagnosis.

Postpartum depression (PPD) is common and disproportionately affects people of color. Experiences of emotional upset due to racism (EUR) may be an important predictor of PPD outcomes. Therefore, we aimed to determine if EUR during the 12 months before delivery was associated with PPD symptomology, asking for help for depression, and depression diagnosis among postpartum people of color (PPOC). We conducted a cross-sectional secondary data analysis among PPOC from 11 states and New York City using PRAMS data, 1/1/2015-12/31/2017. We assessed symptomology using an unvalidated PHQ-2. Logistic regression was performed without and with stratification by ethnicity (non-Hispanic PPOC vs Hispanic PPOC) to estimate whether EUR during 12 months before delivery was associated with (1) PPD symptoms, (2) asking for help for depression, and (3) depression diagnosis. Models adjusted for age, educational attainment, timely prenatal care, payment method, stress during pregnancy, and pre-pregnancy depression. Seventy-four thousand nine hundred nine (11.8%) PPOC reported EUR in the 12 months before delivery. After adjustment, EUR was associated with a 10.3 percentage point (%pt; 95% CI: 6.8, 13.8), 13.6%pt (95% CI: 8.8, 18.5), and 4.1%pt (95% CI: 1.4, 8.0) higher probability of positive PPD screening among all PPOC, non-Hispanic PPOC, and Hispanic PPOC, respectively. EUR was not associated with asking for help for depression but was associated with a higher prevalence of depression diagnosis among all PPOC (4.6%pt; 95% CI: 1.0, 8.4) and non-Hispanic PPOC (6.0%pt; 95% CI: 0.8, 11.2).Experiences of EUR are associated with an increased prevalence of PPD symptoms. Additional prospective research spanning the pre-pregnancy through postpartum periods is needed to examine the dynamic relationship between racism, symptomology, help-seeking, and diagnosis of depression.

The SINEB1 element in the long non-coding RNA Malat1 is necessary for TDP-43 proteostasis.

Transposable elements (TEs) comprise a large proportion of long non-coding RNAs (lncRNAs). Here, we employed CRISPR to delete a short interspersed nuclear element (SINE) in Malat1, a cancer-associated lncRNA, to investigate its significance in cellular physiology. We show that Malat1 with a SINE deletion forms diffuse nuclear speckles and is frequently translocated to the cytoplasm. SINE-deleted cells exhibit an activated unfolded protein response and PKR and markedly increased DNA damage and apoptosis caused by dysregulation of TDP-43 localization and formation of cytotoxic inclusions. TDP-43 binds stronger to Malat1 without the SINE and is likely 'hijacked' by cytoplasmic Malat1 to the cytoplasm, resulting in the depletion of nuclear TDP-43 and redistribution of TDP-43 binding to repetitive element transcripts and mRNAs encoding mitotic and nuclear-cytoplasmic regulators. The SINE promotes Malat1 nuclear retention by facilitating Malat1 binding to HNRNPK, a protein that drives RNA nuclear retention, potentially through direct interactions of the SINE with KHDRBS1 and TRA2A, which bind to HNRNPK. Losing these RNA-protein interactions due to the SINE deletion likely creates more available TDP-43 binding sites on Malat1 and subsequent TDP-43 aggregation. These results highlight the significance of lncRNA TEs in TDP-43 proteostasis with potential implications in both cancer and neurodegenerative diseases.

LGR6 marks nephron progenitor cells.

BACKGROUND: Nephron progenitor cells (NPCs) undergo a stepwise process to generate all mature nephron structures. Mesenchymal to epithelial transition (MET) is considered a multistep process of NPC differentiation to ensure progressive establishment of new nephrons. However, despite this important role, to date, no marker for NPCs undergoing MET in the nephron exists. RESULTS: Here, we identify LGR6 as a NPC marker, expressed in very early cap mesenchyme, pre-tubular aggregates, renal vesicles, and in segments of S-shaped bodies, following the trajectory of MET. By using a lineage tracing approach in embryonic explants in combination with confocal imaging and single-cell RNA sequencing, we provide evidence for the multiple fates of LGR6+ cells during embryonic nephrogenesis. Moreover, by using long-term in vivo lineage tracing, we show that postnatal LGR6+ cells are capable of generating the multiple lineages of the nephrons. CONCLUSIONS: Given the profound early mesenchymal expression and MET signature of LGR6+ cells, together with the lineage tracing of mesenchymal LGR6+ cells, we conclude that LGR6+ cells contribute to all nephrogenic segments by undergoing MET. LGR6+ cells can therefore be considered an early committed NPC population during embryonic and postnatal nephrogenesis with potential regenerative capability.

Pathways to Registered Nursing: Influences of Health-Related Work Experience and Education Financing.

A larger and more diverse registered nurse (RN) workforce in the U.S. is needed to meet growing demand and address social determinants of health and improve health equity. To improve understanding of pathways and barriers to becoming an RN, this study examined prior health care employment and financial assistance factors associated with completion of pre-licensure RN education programs, by initial entry degree (associate degree or bachelor of science in nursing) and across racial and ethnic groups, using the 2018 National Sample Survey of Registered Nurses. The study found higher percentages of associate degree-entry RNs held a health-related job prior to completing their initial RN program than did bachelor's degree entrants. Employer support for education financing as well as reliance on loans and scholarships increased among RNs graduating in 2000 and later, and reliance on self-financing was reported less frequently. Hispanic associate degree-entry RNs reported education financing from only federal loans more frequently compared with White RNs, and higher percentages of Black, multiracial, and "some other race" baccalaureate degree entry RNs accessed federal loans compared with White baccalaureate degree-entry RNs. These findings indicate diversifying the RN workforce should remain a priority to increase representation by underrepresented racial and ethnic groups. Equitable pathways into the RN profession will be facilitated and expedited through policies that overcome financial and social barriers that enable individuals from population groups underrepresented in the nursing workforce to identify with the RN role and route to the profession.

Phenotypic and protein localization heterogeneity associated with AHDC1 pathogenic protein-truncating alleles in Xia-Gibbs syndrome.

Xia-Gibbs syndrome (XGS) is a rare Mendelian disease typically caused by de novo stop-gain or frameshift mutations in the AT-hook DNA binding motif containing 1 (AHDC1) gene. Patients usually present in early infancy with hypotonia and developmental delay and later exhibit intellectual disability (ID). The overall presentation is variable, however, and the emerging clinical picture is still evolving. A detailed phenotypic analysis of 34 XGS individuals revealed five core phenotypes (delayed motor milestones, speech delay, low muscle tone, ID, and hypotonia) in more than 80% of individuals and an additional 12 features that occurred more variably. Seizures and scoliosis were more frequently associated with truncations that arise before the midpoint of the protein although the occurrence of most features could not be predicted by the mutation position. Transient expression of wild type and different patient truncated AHDC1 protein forms in human cell lines revealed abnormal patterns of nuclear localization including a diffuse distribution of a short truncated form and nucleolar aggregation in mid-protein truncated forms. Overall, both the occurrence of variable phenotypes and the different distribution of the expressed protein reflect the heterogeneity of this syndrome.

The broad phenotypic spectrum of PPP2R1A-related neurodevelopmental disorders correlates with the degree of biochemical dysfunction.

PURPOSE: Neurodevelopmental disorders (NDD) caused by protein phosphatase 2A (PP2A) dysfunction have mainly been associated with de novo variants in PPP2R5D and PPP2CA, and more rarely in PPP2R1A. Here, we aimed to better understand the latter by characterizing 30 individuals with de novo and often recurrent variants in this PP2A scaffolding Aα subunit. METHODS: Most cases were identified through routine clinical diagnostics. Variants were biochemically characterized for phosphatase activity and interaction with other PP2A subunits. RESULTS: We describe 30 individuals with 16 different variants in PPP2R1A, 21 of whom had variants not previously reported. The severity of developmental delay ranged from mild learning problems to severe intellectual disability (ID) with or without epilepsy. Common features were language delay, hypotonia, and hypermobile joints. Macrocephaly was only seen in individuals without B55α subunit-binding deficit, and these patients had less severe ID and no seizures. Biochemically more disruptive variants with impaired B55α but increased striatin binding were associated with profound ID, epilepsy, corpus callosum hypoplasia, and sometimes microcephaly. CONCLUSION: We significantly expand the phenotypic spectrum of PPP2R1A-related NDD, revealing a broader clinical presentation of the patients and that the functional consequences of the variants are more diverse than previously reported.

Investigating the Atomic and Mesoscale Interactions that Facilitate Spider Silk Protein Pre-Assembly.

Black widow spider dragline silk is one of nature's high-performance biological polymers, exceeding the strength and toughness of most man-made materials including high tensile steel and Kevlar. Major ampullate (Ma), or dragline silk, is primarily comprised of two spidroin proteins (Sp) stored within the Ma gland. In the native gland environment, the MaSp1 and MaSp2 proteins self-associate to form hierarchical 200-300 nm superstructures despite being intrinsically disordered proteins (IDPs). Here, dynamic light scattering (DLS), three-dimensional (3D) triple resonance solution NMR, and diffusion NMR is utilized to probe the MaSp size, molecular structure, and dynamics of these protein pre-assemblies diluted in 4 M urea and identify specific regions of the proteins important for silk protein pre-assembly. 3D NMR indicates that the Gly-Ala-Ala and Ala-Ala-Gly motifs flanking the poly(Ala) runs, which comprise the ß-sheet forming domains in fibers, are perturbed by urea, suggesting that these regions may be important for silk protein pre-assembly stabilization.

Neurologic Complications of Poverty: the Associations Between Poverty as a Social Determinant of Health and Adverse Neurologic Outcomes.

PURPOSE OF REVIEW: Increasing attention has been paid in recent decades to social determinants of health as a risk factor for disease development and disease severity. While traditionally heart disease, family history, lipid profile, and tobacco use have all been associated with increased risk of neurological disease, numerous studies now show that the influence of poverty may be just as strong a risk factor. This study summarizes the recent literature on poverty as it contributes to neurological disease. RECENT FINDINGS: Children growing up in poverty have increased risk for cognitive deficits and behavioral disorders as reported by Noble et al. (Dev Sci. 9(6):642-54, 2006) and Farah et al. (Brain Res. 1110(1):166-74, 2006) as well as worse outcomes when it comes to epilepsy management and disease course as discussed by Camfield et al. (Epilepsia. 57(11):1826-33, 2016). In adulthood, as the number of social determinants of health increases, the incidence of stroke and severe stroke increases significantly as reported by Reshetnyak et al. (Stroke. 51:2445-53, 2020) as does exposure to neurologically significant infectious diseases and incidence of dementia as reported by Sumilo et al. (Rev Med Virol. 18(2):81-95, 2008) and Zuelsdorff et al. (Alzheimer's Dement. 6(1):e12039, 2020). Social determinants of health including poverty should be considered a risk factor for disease. More attention is needed from clinicians as well as from a public health perspective to address this disparity.

Audiologic Profiles of Children With Otitis Media With Effusion.

OBJECTIVES: To describe the impact of effusion volume, viscosity, and purulence on the audiologic profiles of children with otitis media with effusion. DESIGN: Fifty-one ears from children between the ages of 8 months and 11 years who had a diagnosis of otitis media with effusion and were scheduled for tympanostomy tube placement were recruited from medical clinics. The control group consisted of 17 ears from children between the ages of 10 months and 11 years without a recent history of otitis media and were recruited from a database of research volunteers. Participants received a comprehensive audiologic testing battery consisting of tympanometry, otoacoustic emissions, behavioral audiometric thresholds, and auditory brainstem response testing. For children with otitis media, this testing battery occurred 1 to 2 days before surgery. Middle ear effusions were characterized and collected on the day of surgery during tympanostomy tube placement from ears with otitis media with effusion. The comprehensive audiologic testing battery was completed postoperatively as well for most participants. RESULTS: Effusion volume, categorized in each ear as clear, partial, or full, effected the audiologic results. Ears with full effusions had moderate hearing losses, few to no measurable otoacoustic emissions, and delayed Wave V latencies. Ears with partial effusions and clear ears both had slight to mild hearing losses and normal Wave V latencies, though ears with partial effusions had fewer measurable otoacoustic emissions than clear ears. Normal-hearing control ears with no recent history of otitis media with effusion demonstrated normal audiometric thresholds, present otoacoustic emissions, and normal Wave V latencies. Repeat postoperative testing demonstrated improvements in audiologic testing results for all of the otitis media with effusion volume groups, with no significant differences remaining between the three otitis media with effusion groups. However, significant differences between otitis media with effusion ears and normal-hearing control ears persisted postoperatively, with otitis media with effusion ears demonstrating significantly poorer audiometric thresholds and reduced otoacoustic emissions as compared to normal control ears. The effect of effusion viscosity and purulence could not be systematically evaluated because minimal variability in effusion viscosity and purulence was observed in our sample, with nearly all effusions being mucoid and nonpurulent. CONCLUSIONS: Effusion volume observed at the time of tympanostomy tube surgery was found to play a significant role in outcomes and responses on a range of audiologic tests that compose the standard clinical pediatric audiologic assessment battery. Full middle ear effusions were associated with a moderate hearing loss, and few to no measurable otoacoustic emissions were detected. Ears with a recent diagnosis of otitis media with effusion but clear at the time of tympanostomy tube placement had less hearing loss and a greater number of present otoacoustic emissions than ears with full or partial effusions but were still found to have poorer hearing sensitivity than the healthy control ears. Differences between ears with otitis media with effusion and healthy control ears persisted on postoperative assessments of otoacoustic emissions and audiometric thresholds, though there were no remaining effects of the presurgical effusion volume group.

Restorative Quality Improvement: Novel Application of Six Sigma in a Skilled Nursing Facility.

BACKGROUND: Six Sigma is a quality improvement (QI) method used in hospitals, but not typically in nursing homes (NHs), to reduce service variability and expenditures. LOCAL PROBLEM: The existing QI process for functional maintenance program (FMP) charting/auditing in an urban NH allowed variability and lost revenue. METHODS: A single-group pre/posttest design with analysis of variance and t-test analysis was used to implement Six Sigma for the FMP process. INTERVENTION: Phases of Define, Measure, Analyze, Improve, and Control addressed performance objectives of FMP capacity; staff retention; congruence between prescribed, performed, and charted FMPs; and month-end summaries of resident status on FMPs. RESULTS: With the existing staff, capability was increased by 17 residents ($200 000 revenue) and 90% to 100% charting congruence was achieved. Limited success was attributed to lack of skill diffusion, team communication, manager availability, and project prioritization. CONCLUSIONS: Six Sigma was moderately successful when applied in a single NH for QI.

Compliance and Related Outcomes of Prophylactic Antibiotics in Traumatic Open Fractures.

Purpose: Prophylactic antibiotic therapy is a standard of care for patients who present with open fractures due to the risk of infectious complications. This study was conducted to characterize the use of initial prophylactic antibiotic use in open fractures, guideline compliance, and its impact on care. Methods: Retrospective chart review of adult patients presenting with an open fracture to a Level 1 Trauma Center Emergency Department over a 12-month period was conducted. Results: Of the 202 patients meeting inclusion criteria, overall compliance with guideline recommendations for antibiotic prophylaxis was found to be 33.2%. The duration of prophylactic therapy was significantly longer in the noncompliant group and among those who received a secondary antibiotic (P < .05 for both comparisons). The duration of therapy was found to be significantly longer in those patients who developed an infection (P < .001). Those who developed an infection had a longer hospital length of stay (LOS) (P < .001) and intensive care unit LOS (P = .002). In addition, those who developed an infection had significantly more surgeries (P < .001) and received more red blood cell transfusions (P < .001). Correlation analysis confirmed a significant association between infection and duration of antibiotic prophylaxis (P = .02), number of surgeries (P < .0001), and number of transfusions (P < .0001). Conclusion: Guideline compliance was exceedingly low due to the extended duration of initial antibiotic therapy and did not appear to yield any clinical benefits. Infection was significantly associated with longer duration of initial prophylactic therapy and morbidity. Opportunities exist to elevate compliance with guidelines and to reevaluate prophylactic antimicrobial therapy in this setting.

Outcome measures in pediatric polypharmacy research: a scoping review.

INTRODUCTION: Various methods have been used to interpret the reports of pediatric polypharmacy across the literature. This is the first scoping review that explores outcome measures in pediatric polypharmacy research. OBJECTIVES: The aim of our study was to describe outcome measures assessed in pediatric polypharmacy research. METHODS: A search of electronic databases was conducted in July 2017, including Ovid Medline, PubMed, Elsevier Embase, Wiley Cochrane Central Register of Controlled Trials (CENTRAL), EBSCO CINAHL, Ovid PsyclNFO, Web of Science Core Collection, ProQuest Dissertations and Thesis A&I. Data were extracted about study characteristics and outcome measures, and also synthesized by harms or benefits mentioned. RESULTS: The search strategy initially identified 8169 titles and screened 4398 using the inclusion criteria after de-duplicating. After the primary screening, a total of 363 studies were extracted for the data analysis. Polypharmacy (prevalence) was identified as an outcome in 31.4% of the studies, prognosis-related outcomes in 25.6%, and adverse drug reactions in 16.5%. A total of 265 articles (73.0%) mentioned harms, including adverse drug reactions (26.4%), side effects (24.2%), and drug-drug interactions (20.9%). A total of 83 studies (22.9%) mentioned any benefit, 48.2% of which identified combination for efficacy, 24.1% combination for treatment of complex diseases, and 19.3% combination for treatment augmentation. Thirty-eight studies reported adverse drug reaction as an outcome, where polypharmacy was a predictor, with various designs. CONCLUSIONS: Most studies of pediatric polypharmacy evaluate prevalence, prognosis, or adverse drug reaction-related out-comes, and underscore harms related to polypharmacy. Clinicians should carefully weigh benefits and harms when introducing medications to treatment regimens.