Periodontal disease is not associated with risk of inflammatory bowel disease: Results from two prospective cohort studies in the US.

AIM: To examine the relationship between periodontal disease and tooth loss and risk of inflammatory bowel disease (IBD). METHODS: We conducted a prospective cohort study of 86,602 women from the Nurses' Health Study (1992-2016) and 50,349 men from the Health Professionals Follow-up Study (1986-2016) with available data on periodontal disease and tooth loss. Cases of IBD were initially reported by participants and then confirmed by medical record review. We used Cox proportional hazards modelling to estimate multivariable-adjusted hazard ratios (aHRs) and 95% CIs. RESULTS: Through the end of follow-up, we documented 175 cases of Crohn's disease (CD) and 209 cases of ulcerative colitis (UC). After adjustment for potential risk factors, there was no association between periodontal disease and risk of CD (pooled aHR: 0.99, 95% CI: 0.65-1.52, p = 0.970) or UC (aHR: 0.99, 95% CI: 0.68-1.45, p = 0.971). Similarly, we did not observe an association between tooth loss and risk of CD (aHR: 0.72, 95% CI: 0.43-1.21, p = 0.218) or UC (aHR: 0.89, 95% CI: 0.58-1.36, p = 0.581) in the pooled analysis. The associations were not modified by sex, age, body mass index (BMI), smoking status or NSAID use (all pinteraction > 0.87). CONCLUSION: In two large prospective cohort studies, we did not observe an association between periodontal disease and tooth loss and risk of CD or UC.

DRAK2 contributes to type 1 diabetes by negatively regulating IL-2 sensitivity to alter regulatory T cell development.

Drak2-deficient (Drak2-/-) mice are resistant to multiple models of autoimmunity yet effectively eliminate pathogens and tumors. Thus, DRAK2 represents a potential target to treat autoimmune diseases. However, the mechanisms by which DRAK2 contributes to autoimmunity, particularly type 1 diabetes (T1D), remain unresolved. Here, we demonstrate that resistance to T1D in non-obese diabetic (NOD) mice is due to the absence of Drak2 in T cells and requires the presence of regulatory T cells (Tregs). Contrary to previous hypotheses, we show that DRAK2 does not limit TCR signaling. Rather, DRAK2 regulates IL-2 signaling by inhibiting STAT5A phosphorylation. We further demonstrate that enhanced sensitivity to IL-2 in the absence of Drak2 augments thymic Treg development. Overall, our data indicate that DRAK2 contributes to autoimmunity in multiple ways by regulating thymic Treg development and by impacting the sensitivity of conventional T cells to Treg-mediated suppression.

Design and implementation of a cluster randomized trial measuring benefits of medical scribes in the VA.

BACKGROUND: Medical scribes are trained professionals who assist health care providers by administratively expediting patient encounters. Section 507 of the MISSION Act of 2018 mandated a 2-year study of medical scribes in VA Medical Centers (VAMC). This study began in 2020 in the emergency departments and specialty clinics of 12 randomly selected VAMCs across the country, in which 48 scribes are being deployed. METHODS: We are using a cluster randomized trial to assess the effects of medical scribes on productivity (visits and relative value units [RVUs]), wait times, and patient satisfaction in selected specialties within the VA that traditionally have high wait times. Scribes will be assigned to emergency departments and/or specialty clinics (cardiology, orthopedics) in VAMCs randomized into the intervention. Remaining sites that expressed interest but were not randomized to the intervention will be used as a comparison group. RESULTS: Process measures from early implementation of the trial indicate that contracting may hold an advantage over direct hiring in terms of reaching staffing targets, although onboarding contractor scribes has taken somewhat longer (from job posting to start date). CONCLUSIONS: Our evaluation findings will provide insight into whether scribes can increase provider productivity and decrease wait times for high demand specialties in the VA without adversely affecting patient satisfaction. IMPLICATIONS: As a learning health care system, this trial has great potential to increase our understanding of the potential effects of scribes while also informing a real policy problem in high wait times and provider administrative burdens.

Learning from others: A low-cost-high-impact risk/opportunity identification technique.

News for risk/opportunity identification (NfROI) is a tool for practitioners to leverage the journey from a risk management mindset to an enterprise risk management approach. NfROI unleashes the power of storytelling and provides a standardized format to enhance the existing practice of gleaning information from sources such as JHRM, news outlets, social media, and the ASHRM Exchange. A series of 3 examples highlight the advantages of learning from others as a complement to retrospective internal data. The stories have implications across the ASHRM's ERM Framework domains and thereby provide bridges across the pillars in the organizational chart. Learning from others can reduce costs and reveal emerging risks before the direct impact on the organization.

Agreement of sleep specialists with registered nurses' sleep study orders in supervised clinical practice.

STUDY OBJECTIVES: Incorporating registered nurses (RN-level) into obstructive sleep apnea (OSA) management decisions has the potential to augment the workforce and improve patient access, but the appropriateness of such task-shifting in typical practice is unclear. METHODS: Our medical center piloted a nurse triage program for sleep medicine referrals. Using a sleep specialist-designed decision-making tool, nurses triaged patients referred for initial sleep studies to either home sleep apnea test (HSAT) or in-laboratory polysomnography (PSG). During the first 5 months of the program, specialists reviewed all nurse triages. We compared agreement between specialists and nurses. RESULTS: Of 280 consultations triaged by nurses, nurses deferred management decisions to sleep specialists in 6.1% (n = 17) of cases. Of the remaining 263 cases, there was 88% agreement between nurses and specialists (kappa 0.80, 95% confidence interval 0.74-0.87). In the 8.8% (n = 23) of cases where supervising specialists changed sleep study type, specialists changed from HSAT to PSG in 16 cases and from PSG to HSAT in 7. The most common indication for change in sleep study type was disagreement regarding OSA pretest probability (n = 14 of 23). Specialists changed test instructions in 3.0% (n = 8) of cases, with changes either related to the use of transcutaneous carbon dioxide monitoring (n = 4) or adaptive servo-ventilation (n = 4). CONCLUSIONS: More than 80% of sleep study triages by registered nurses in a supervised setting required no sleep specialist intervention. Future research should focus on how to integrate nurses into the sleep medicine workforce in a manner that maximizes efficiency while preserving or improving patient outcomes.

Effects of Acute and Chronic Exposure to Residual Level Erythromycin on Human Intestinal Epithelium Cell Permeability and Cytotoxicity.

Residual concentrations of erythromycin in food could result in gastrointestinal tract exposure that potentially poses a health-hazard to the consumer, affecting intestinal epithelial permeability, barrier function, microbiota composition, and antimicrobial resistance. We investigated the effects of erythromycin after acute (48 h single treatment with 0.03 µg/mL to 300 µg/mL) or chronic (repeated treatment with 0.3 µg/mL and 300 µg/mL erythromycin for five days) exposures on the permeability of human colonic epithelial cells, a model that mimics a susceptible intestinal surface devoid of commensal microbiota. Transepithelial electrical resistance (TER) measurements indicated that erythromycin above 0.3 µg/mL may compromise the epithelial barrier. Acute exposure increased cytotoxicity, while chronic exposure decreased the cytotoxicity. Quantitative PCR analysis revealed that only ICAM1 (intercellular adhesion molecule 1) was up-regulated during 0.3 µg/mL acute-exposure, while ICAM1, JAM3 (junctional adhesion molecule 3), and ITGA8 (integrin alpha 8), were over-expressed in the 300 µg/mL acute treatment group. However, during chronic exposure, no change in the mRNA expression was observed at 0.3 µg/mL, and only ICAM2 was significantly up-regulated after 300 µg/mL. ICAM1 and ICAM2 are known to be involved in the formation of extracellular matrices. These gene expression changes may be related to the immunoregulatory activity of erythromycin, or a compensatory mechanism of the epithelial cells to overcome the distress caused by erythromycin due to increased permeability.

Assessment of barriers and facilitators in the implementation of appropriate use criteria for elective percutaneous coronary interventions: a qualitative study.

BACKGROUND: The use of inappropriate elective Percutaneous Coronary Intervention (PCI) has decreased over time, but hospital-level variation in the use of inappropriate PCI persists. Understanding the barriers and facilitators to the implementation of Appropriate Use Criteria (AUC) guidelines may inform efforts to improve elective PCI appropriateness. METHODS: All hospitals performing PCI in Washington State were categorized by their use of inappropriate elective PCI in 2010 to 2013. Semi-structured, qualitative telephone interviews were then conducted with 17 individual interviews at 13 sites in Washington State to identify barriers and facilitators to the implementation of the AUC guidelines. An inductive and deductive, team-based analytical approach, drawing primarily on Matrix analysis was performed to identify factors affecting implementation of the AUC. RESULTS: Specific facilitators were identified that supported successful implementation of the AUC. These included collaborative catheterization laboratory environments that allow all staff to participate with questions and opinions; ongoing AUC education with catheterization laboratory teams and referring providers; internal AUC peer review processes; interventional cardiologist be directly involved with the pre-procedural review process; checklist-based algorithms for pre-procedural documentation; systems redesign to include insurance companies; and AUC educational information with patients. Barriers to implementation of the AUC included external pressures, such as competition for patients, and the lack of shared medical records with sites that referred patients for coronary angiography. CONCLUSIONS: The identified facilitators enabled sites to successfully implement the AUC. Catheterization laboratories struggling to successfully implement the AUC may consider utilizing these strategies to improve their processes to improve patient selection for elective PCI.

Perspectives on a Home Telehealth Care Management Program for Veterans With Posttraumatic Stress Disorder Who Smoke.

BACKGROUND: Individuals with posttraumatic stress disorder (PTSD) have high rates of smoking and low quit rates. We conducted a qualitative evaluation of an integrated smoking cessation randomized controlled trial (RCT) that used home telehealth and motivational interviewing (MI) to change smoking behaviors among individuals with PTSD. METHOD: Using a convenience sample sourced from the original RCT, intervention and control group participants were invited to participate in a qualitative evaluation. Semistructured interview guides were used to assess the effectiveness of study components, make recommendations for future interventions, and identify facilitators/barriers to smoking cessation. We analyzed these data using an inductive and deductive, team-based content analysis approach. RESULTS: We interviewed 32 study participants (intervention: n = 15, control: n = 17) who completed the original RCT within the previous 6 months. Respondents were highly satisfied with home telehealth and MI counseling. The intervention group respondents found MI counseling to be supportive, nonjudgmental, and informative. Control group respondents felt that they had received smoking cessation assistance. Respondents from both groups desired more information about PTSD and smoking, relied on smoking as a coping mechanism for PTSD, and believed that quitting was an individual choice. CONCLUSION: Respondents reported that home telehealth and MI were acceptable ways to provide smoking cessation assistance to individuals with PTSD. The support and increased awareness of smoking behaviors were perceived as helpful. Future investigations should focus on increasing support and information about stress management, smoking, PTSD, and the relationship between them for individuals with PTSD who smoke.

Evaluation of the Veterans Health Administration's Specialty Care Transformational Initiatives to Promote Patient-Centered Delivery of Specialty Care: A Mixed-Methods Approach.

INTRODUCTION: Veteran's Affairs Office of Specialty Care (OSC) launched four national initiatives (Electronic-Consults [e-Consults], Specialty Care Access Networks-Extension for Community Healthcare Outcomes [SCAN-ECHO], Mini-Residencies, and Specialty Care Neighborhood) to improve specialty care delivery and funded a center to evaluate the initiatives. METHODS: The evaluation, guided by two implementation frameworks, provides formative (administrator/provider interviews and surveys) and summative data (quantitative data on patterns of use) about the initiatives to OSC. RESULTS: Evaluation of initiative implementation is assessed through CFIR (Consolidated Framework for Implementation Research)-grounded qualitative interviews to identify barriers/facilitators. Depending on high or low implementation, factors such as receiving workload credit, protected time, existing workflow/systems compatibility, leadership engagement, and access to information/resources were considered implementation barriers or facilitators. Findings were shared with OSC and used to further refine implementation at additional sites. Evaluation of other initiatives is ongoing. CONCLUSIONS: The mixed-methods approach has provided timely information to OSC about initiative effect and impacted OSC policies on implementation at additional sites.

The Veterans Health Administration's proposal for APRN full-practice authority.

The Veterans Health Administration (VHA) is proposing full-practice authority for advanced practice registered nurses (APRNs) to improve access, care delivery, and patient choice, as well as reduce costs. The authors performed a mixed-methods assessment to obtain the perspectives of administrators and APRNs on the characterization of the APRN workforce and their present practice in the VHA.

Size and dose dependent effects of silver nanoparticle exposure on intestinal permeability in an in vitro model of the human gut epithelium.

BACKGROUND: The antimicrobial activity of silver nanoparticles (AgNP) has led to interest in their use in consumer products such as food contact materials, utensils, and storage containers. Incorporation of these materials into items intended for food processing and storage suggests that consumer use of these products could result in gastrointestinal exposure to AgNP, should the nanoparticles migrate from the product. The health impact of AgNP exposure is unknown, especially effects related to intestinal epithelial permeability and barrier function. This study examined the effects of AgNP exposure of different sizes (10, 20, 75 and 110 nm) and doses (20 and 100 µg/mL) on the permeability of T84 human colonic epithelial cells, which serve as an in vitro model of the human gut epithelium. RESULTS: Results showed that effects of AgNP on the T84 epithelial cells were size- and dose-dependent, with the 10 nm AgNP causing the most significant changes. Changes in permeability of the epithelial cell monolayer, as measured by transepithelial electrical resistance, after exposure to 10 nm AgNP were most dramatic at the highest dose (100 µg/mL), but also observed at the lower dose (20 µg/mL). AgNP could be visualized inside cells using transmission electron microscopy and silver was detected in basal wells using inductively coupled plasma-mass spectrometry. Exposure to AgNP significantly affected the expression of genes involved in anchoring tight junctions, cellular proliferation and signaling, endocytosis, and cell-cell adhesion, with the 10 nm AgNP having the greatest effect. CONCLUSIONS: The results of this study show that small-size AgNP have significant effects on intestinal permeability in an in vitro model of the human gastrointestinal epithelium. Such effects have the potential to compromise the integrity of the intestinal epithelium and this disruption of barrier function could have health consequences for the gastrointestinal tract.

Dose and Size-Dependent Antiviral Effects of Silver Nanoparticles on Feline Calicivirus, a Human Norovirus Surrogate.

OBJECTIVES: Silver nanoparticles (AgNPs) as antibacterial agents are incorporated in many consumer products, while the use as antiviral agents is an ongoing area of research. We evaluated the antiviral properties of AgNPs of variable sizes (10, 75, and 110 nm) and doses (25, 50, and 100 µg/mL) at different contact time points against feline calicivirus (FCV), a surrogate for norovirus. MATERIALS AND METHODS: Antiviral effects of the AgNPs were determined by comparing the infectivity of FCV, the appearance of cytopathic effects (CPEs), and the integrity of the viral capsid protein in viral suspension treated with AgNPs with the untreated controls. RESULTS: The 10 nm AgNPs at 50 and 100 µg/mL concentrations inactivated the FCV beyond the limit of detection, resulting in a decrease of up to 6.5 log10 viral titer, prevented development of CPEs, and reduction in the western blot band signal of the viral capsid protein. No significant antiviral effect was observed for the 75 and 110 nm AgNPs. Conclusions and Applications: These results demonstrate that the antiviral effects of AgNPs are both size and dose dependent, thus potential applications of AgNPs as antiviral agents to prevent contamination of foodborne viruses need to consider size and dose effects.

A new method for identifying informative genetic markers in selectively bred rats.

Microsatellite length polymorphisms are useful for the mapping of heritable traits in rats. Over 4000 such microsatellites have been characterized for 48 inbred rat strains and used successfully to map phenotypes that differ between strains. At present, however, it is difficult to use this microsatellite database for mapping phenotypes in selectively bred rats of unknown genotype derived from outbred populations because it is not immediately obvious which markers might differ between strains and be informative. We predicted that markers represented by many alleles among the known inbred rat strains would also be most likely to differ between selectively bred strains derived from outbred populations. Here we describe the development and successful application of a new genotyping tool (HUMMER) that assigns "heterozygosity" (Het) and "uncertainty" (Unc) scores to each microsatellite marker that corresponds to its degree of heterozygosity among the 48 genotyped inbred strains. We tested the efficiency of HUMMER on two rat strains that were selectively bred from an outbred Sprague-Dawley stock for either high or low activity in the forced swim test (SwHi rats and SwLo rats, respectively). We found that the markers with high Het and Unc scores allowed the efficient selection of markers that differed between SwHi and SwLo rats, while markers with low Het and Unc scores typically identified markers that did not differ between strains. Thus, picking markers based on Het and Unc scores is a valuable method for identifying informative microsatellite markers in selectively bred rodent strains derived from outbred populations.

Interference in the Coomassie Brilliant Blue and Pyrogallol Red protein dye-binding assays is increased by the addition of sodium dodecyl sulfate to the dye reagents.

We have investigated the effect of sodium dodecyl sulfate (SDS) upon the response of the Coomassie Brilliant Blue (CBB) and Pyrogallol Red-molybdate (PRM) protein dye-binding assays to interference from aminoglycosides, ampholytes, detergents, phenothiazines, reducing agents, and miscellaneous substances previously reported to interfere with the assays. The CBB assay was less prone to interference than the PRM assay but gave positive interference with the detergents and the phenothiazines and negative interference with dextran sulfate. The PRM assay gave positive interference with the aminoglycosides, ampholytes, and phenothiazines and negative interference with SDS, citric acid, dextran sulfate, EDTA, oxalic acid, and tartaric acid. The level of interference varied in the presence of different proteins (albumin, gamma globulin, alpha1-acid glycoprotein, or lysozyme) and increased when SDS was added to the dye reagents.

An evaluation of protein assays for quantitative determination of drugs.

We have evaluated the response of six protein assays [the biuret, Lowry, bicinchoninic acid (BCA), Coomassie Brilliant Blue (CBB), Pyrogallol Red-Molybdate (PRM), and benzethonium chloride (BEC)] to 21 pharmaceutical drugs. The drugs evaluated were analgesics (acetaminophen, aspirin, codeine, methadone, morphine and pethidine), antibiotics (amoxicillin, ampicillin, gentamicin, neomycin, penicillin G and vancomycin), antipsychotics (chlorpromazine, fluphenazine, prochlorperazine, promazine and thioridazine) and water-soluble vitamins (ascorbic acid, niacinamide, pantothenic acid and pyridoxine). The biuret, Lowry and BCA assays responded strongly to most of the drugs tested. The PRM assay gave a sensitive response to the aminoglycoside antibiotics (gentamicin and neomycin) and the antipsychotic drugs. In contrast, the CBB assay showed little response to the aminoglycosides and gave a relatively poor response with the antipsychotics. The BEC assay did not respond significantly to the drugs tested. The response of the protein assays to the drugs was further evaluated by investigating the linearity of the response and the combined response of drug plus protein. The results are discussed with reference to drug interference in protein assays and the development of new methods for the quantification of drugs in protein-free solution.