An Electronic Shared Decision-Making App to Improve Asthma Outcomes: A Randomized Controlled Trial.

BACKGROUND: Shared decision-making (SDM) incorporates patient values and preferences to optimize asthma management decisions. Available asthma SDM aids primarily focus on medication selection. OBJECTIVE: To assess the usability, acceptability, and preliminary effectiveness of an electronic SDM application, the ACTION (Active Conversation in asthma Treatment shared decisION-making) app, that addressed medication, nonmedication, and COVID-19 concerns for asthma. METHODS: In this pilot study, 81 participants with asthma were randomized into the control arm or ACTION app intervention. The ACTION app was completed 1 week before a clinic visit, and responses were shared with the medical provider. The primary outcomes were patient satisfaction and SDM quality. Next, ACTION app users (n = 9) and providers (n = 5) provided feedback through separate virtual focus groups. Sessions were coded by comparative analysis. RESULTS: The ACTION app group scored higher agreement that providers adequately addressed COVID-19 concerns compared with the control group (4.4 vs 3.7, P = .03). Although the ACTION app group had a higher total 9-item Shared Decision-Making Questionnaire score, this did not reach statistical significance (87.1 vs 83.3, P = .2). However, the ACTION app group demonstrated stronger agreement that their physician knew exactly how they wanted to be involved in decision-making (4.3 vs 3.8, P = .05), providers asked about preferences (4.3 vs 3.8, P = .05), and that different options were thoroughly weighed (4.3 vs 3.8, P = .03). Major focus group themes included that the ACTION app was practical and established a patient-centered agenda. CONCLUSION: An electronic asthma SDM app that incorporates patient preferences regarding nonmedication-related, medication-related, and COVID-19-related concerns is well accepted and can improve patient satisfaction and SDM.

Single Cell RNA Sequencing Reveals Human Tooth Type Identity and Guides In Vitro hiPSC Derived Odontoblast Differentiation (iOB).

Over 90% of the U.S. adult population suffers from tooth structure loss due to caries. Most of the mineralized tooth structure is composed of dentin, a material produced and mineralized by ectomesenchyme derived cells known as odontoblasts. Clinicians, scientists, and the general public share the desire to regenerate this missing tooth structure. To bioengineer missing dentin, increased understanding of human tooth development is required. Here we interrogate at the single cell level the signaling interactions that guide human odontoblast and ameloblast development and which determine incisor or molar tooth germ type identity. During human odontoblast development, computational analysis predicts that early FGF and BMP activation followed by later HH signaling is crucial. Application of this sci-RNA-seq analysis generates a differentiation protocol to produce mature hiPSC derived odontoblasts in vitro (iOB). Further, we elucidate the critical role of FGF signaling in odontoblast maturation and its biomineralization capacity using the de novo designed FGFR1/2c isoform specific minibinder scaffolded as a C6 oligomer that acts as a pathway agonist. We find that FGFR1c is upregulated in functional odontoblasts and specifically plays a crucial role in driving odontoblast maturity. Using computational tools, we show on a molecular level how human molar development is delayed compared to incisors. We reveal that enamel knot development is guided by FGF and WNT in incisors and BMP and ROBO in the molars, and that incisor and molar ameloblast development is guided by FGF, EGF and BMP signaling, with tooth type specific intensity of signaling interactions. Dental ectomesenchyme derived cells are the primary source of signaling ligands responsible for both enamel knot and ameloblast development.

Understanding the Updates in the Asthma Guidelines.

Asthma is a chronic inflammatory lung disease that affects millions of Americans, with variable symptoms of bronchospasm and obstruction among individuals over time. The National Heart, Lung, and Blood Institute (NHLBI) published the 2020 Focused Updates to the Asthma Management Guidelines based on the latest research since the 2007 Expert Panel Report-3 (EPR-3). The following article reviews the 21 new recommendations on the six core topics in asthma: use of intermittent inhaled corticosteroids, long-acting muscarinic antagonist therapy, use of the fractional exhaled nitric oxide test in asthma diagnosis and monitoring, indoor allergen mitigation, immunotherapy, and bronchial thermoplasty. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate recommendations as strong or conditional based on the evidence. The recommendations were based on systematic reviews of the literature and focused on patient-centered critical outcomes of asthma exacerbations, asthma control, and asthma-related quality of life. Understanding the recommendations with consideration of individual values through shared decision-making may improve asthma outcomes.

Realigning economic incentives for depression care at UCSF.

Behavioral health carve-out arrangements create financial disincentives for primary care providers (PCPs) to treat depression. A novel collaboration between a primary care practice, a health insurer, and a managed behavioral health organization (MBHO) allows PCPs to receive reimbursement and schedule longer appointments to care for depressed patients. This article describes the details of the arrangement, and early results of this collaboration. Early results find that financial incentives are critical for implementation, but that time incentives do not appear to motivate PCPs. Sustainability of this model will require participation of multiple primary care practices, health insurers, and MBHOs.

Role of cyclooxygenase enzymes in a murine model of experimental cholera.

Nonsteroidal anti-inflammatory drugs (e.g., indomethacin) inhibit and reduce the fluid secretion responses elicited by cholera toxin (CT), but it has not been conclusively determined which cyclooxygenase (COX) isoform is involved in CT's action. This study evaluated the role of the COX enzymes and their arachidonic acid metabolites in experimental cholera. Swiss-Webster mice were dosed with celecoxib and rofecoxib and challenged with CT in ligated small intestinal loops, and intestinal segments from mice deficient in COX-1 and COX-2 were challenged with CT. The effects of CT on fluid accumulation, prostaglandin E(2) production, mucosal tissue injury, and markers of oxidative stress were measured. Celecoxib and rofecoxib given at 160 micro g per mouse inhibited CT-induced fluid accumulation by 48% and 31%, respectively, but there was no significant difference among cox-1(-/-) and cox-2(-/-) mice in response to CT compared to wild-type controls. CT elevated tissue levels of oxidized glutathione and lipid peroxides and elicited small intestinal tissue injury in two of five cox-1(-/-) and four of five cox-2(-/-) mice. A role for COX-2 in CT's mechanism of action has previously been suggested by the effectiveness of COX-2 inhibitors in reducing CT-induced fluid secretion, but CT challenge of COX-1 and COX-2 knockout mice did not corroborate the pharmacological data. The results of this study show that CT induced oxidative stress in COX-deficient mice and suggest a tissue-protective role for arachidonic acid metabolites in the small intestine against oxidative stress.

The cox-2-specific inhibitor celecoxib inhibits adenylyl cyclase.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are well-known causes of acute renal insufficiency and gastropathy in patients with chronic inflammatory diseases. This action is presumed to result from nonselective inhibition of both constitutive and inducible forms of prostaglandin H synthases, also known as the cyclooxygenase enzymes (i.e., COX-1 amd COX-2). Celecoxib (Celebrex) is a COX-2 enzyme inhibitor and has emerged as a preferred therapeutic agent for the treatment of rheumatoid arthritis as compared to other NSAIDs. Celecoxib has recently been the subject of criticism for its side effects, mainly arterial thrombosis and renal hemorrhage, although it is considered a superior drug in protecting the gastrointestinal tract. In the present study, we report that celecoxib not only inhibited COX-2, but also exhibited the property of inhibiting adenylyl cyclase, an important enzyme forming the intracellular second messenger 3',5'-adenosine monophosphate (cAMP) from adenosine triphosphate (ATP). Celecoxib also inhibited cholera toxin-stimulated cAMP formation, which indicated its ability to permeate cell membranes in order to reach intracellular adenylyl cyclase. It inhibited in vitro adenylyl cyclase activity in both human colonic epithelial cells and purified adenylyl cyclase from Bordetella pertussis. The IC50 of celecoxib for B. pertussis adenylyl cyclase was calculated to be 0.375 mM. Lineweaver-Burk analysis showed that the type of enzyme inhibition was competitive. The apparent Km and Vm of adenylyl cyclase was calculated as 25.0 nM and 7.14 nmol/min/mg, respectively. Celecoxib changed the Km value to 66.6 nM without affecting the Vmax. The current study suggests that apart from inflammation, celecoxib therapy could be further extended to diseases involving cAMP upregulation either by endogenous reactions or exogenous agents. These new data showing inhibition of adenylyl cyclase should be considered in light of the drug's pathological effects or in patients specifically excluded from treatment (e.g., asthmatics).