Nothing for Me or About Me, Without Me: Codesign of Clinical Decision Support.

BACKGROUND: Partnerships among patients, families, caregivers, and clinicians are critical to helping patients lead their best lives given their specific genetics, conditions, circumstances, and the environments in which they live, work, and play. These partnerships extend to the development of health information technology, including clinical decision support (CDS). Design of these technologies, however, often occurs without a profound understanding of the true needs, wants, and concerns of patients and family members. Patient perspective is important not only for patient-facing applications but for provider-facing applications, especially those intended to support shared decision-making. OBJECTIVES: Our objective is to describe models for effectively engaging patients and caregivers during CDS development and implementation and to inspire CDS developers to partner with patients and caregivers to improve the potential impact of CDS. METHODS: This article serves as a case study of how two patient activists successfully implemented models for engaging patients and caregivers in a federal program designed to increase the uptake of research evidence into clinical practice through CDS. Models included virtual focus groups, social media, agile software development, and attention to privacy and cybersecurity. RESULTS: Impact on the federal program has been substantial and has resulted in improved CDS training materials, new prototype CDS applications, prioritization of new functionality and features, and increased engagement of patient and caregiver communities in ongoing projects. Among these opportunities is a group of developers and patient activists dedicated and committed to exploring strategic and operational opportunities to codesign CDS applications. CONCLUSION: Codesign and implementation of CDS can occur as a partnership among developers, implementers, patients, cybersecurity and privacy activists, and caregivers. Several approaches are viable, and an iterative process is most promising. Additional work is needed to investigate scalability of the approaches explored by this case study and to identify measures of meaningful inclusion of patients/caregivers in CDS projects.

Living Organ Donor Perspectives and Sources of Hesitancy about COVID-19 Vaccines.

BACKGROUND: Living organ donation declined substantially in the United States during the COVID-19 pandemic due to concerns about donor and transplant candidate safety. COVID-19 vaccines might increase confidence in the safety of living organ donation during the pandemic. We assessed informational preferences and perspectives about COVID-19 vaccines among US living organ donors and prospective donors. METHODS: We conducted a national survey study of organ donors and prospective donors on social media platforms between 12/28/2020-2/23/2021. Survey items included multiple choice, visual analog scale, and open-ended responses. We examined associations between information preferences, history of COVID-19 infection, influenza vaccination history and COVID-19 vaccine acceptance using multivariable logistic regression and performed a thematic analysis of open-ended responses. RESULTS: Among 342 respondents from 47 US states and the District of Columbia, 35% were between 51-70 years old, 90% were non-Hispanic white, 87% were women; 82% were living donors (94% kidney) and 18% in evaluation to donate (75% kidney).The majority planned to or had received COVID-19 vaccination (76%), whereas 11% did not plan to be receive a vaccine, and 12% were unsure. Adjusting for demographics and donor characteristics, respondents who receive yearly influenza vaccinations had higher COVID-19 vaccine acceptance than those who do not (adjusted Odds Ratio [aOR] 5.06, 95% Confidence Interval [CI] 2.68-9.53). Compared to respondents who prioritized medical information sources (e.g., personal physicians and transplant providers), those who prioritized news and social media had lower COVID-19 vaccine acceptance (aOR 0.34, 95% CI 0.15-0.73). Low perceived personal benefit from vaccination and uncertainty about long-term safety were common themes among those declining COVID-19 vaccines. CONCLUSIONS: Donor informational source preferences were strongly associated with the likelihood of accepting a COVID-19 vaccine. Vaccine guidance for organ donors who are unsure about COVID-19 vaccines could incorporate messaging about safety and benefits of vaccination for healthy people.

Nomenclature for kidney function and disease: report of a Kidney Disease: Improving Global Outcomes (KDIGO) Consensus Conference.

The worldwide burden of kidney disease is rising, but public awareness remains limited, underscoring the need for more effective communication by stakeholders in the kidney health community. Despite this need for clarity, the nomenclature for describing kidney function and disease lacks uniformity. In June 2019, Kidney Disease: Improving Global Outcomes (KDIGO) convened a Consensus Conference with the goal of standardizing and refining the nomenclature used in the English language to describe kidney function and disease, and of developing a glossary that could be used in scientific publications. Guiding principles of the conference were that the revised nomenclature should be patient-centered, precise, and consistent with nomenclature used in the KDIGO guidelines. Conference attendees reached general consensus on the following recommendations: (i) to use "kidney" rather than "renal" or "nephro-" when referring to kidney disease and kidney function; (ii) to use "kidney failure" with appropriate descriptions of presence or absence of symptoms, signs, and treatment, rather than "end-stage kidney disease"; (iii) to use the KDIGO definition and classification of acute kidney diseases and disorders (AKD) and acute kidney injury (AKI), rather than alternative descriptions, to define and classify severity of AKD and AKI; (iv) to use the KDIGO definition and classification of chronic kidney disease (CKD) rather than alternative descriptions to define and classify severity of CKD; and (v) to use specific kidney measures, such as albuminuria or decreased glomerular filtration rate (GFR), rather than "abnormal" or "reduced" kidney function to describe alterations in kidney structure and function. A proposed 5-part glossary contains specific items for which there was general agreement. Conference attendees acknowledged limitations of the recommendations and glossary, but they considered standardization of scientific nomenclature to be essential for improving communication.

Consistency of Recommendations for Evaluation and Management of Hypertension.

Importance: Hypertension is very common, but guideline recommendations for hypertension have been controversial, are of increasing interest, and have profound implications. Objective: To systematically assess the consistency of recommendations regarding hypertension management across clinical practice guidelines (CPGs). Design, Setting, and Participants: This cross-sectional study of hypertension management recommendations included CPGs that had been published as of April 2018. Two point-of-care resources that provided graded recommendations were included for secondary analyses. Discrete and unambiguous specifications of the population, intervention, and comparison states were used to define a series of reference recommendations. Three raters reached consensus on coding the direction and strength of each recommendation made by each CPG. Three independent raters reached consensus on the importance of each reference recommendation. Main Outcomes and Measures: The main outcomes were rates of consistency for direction and strength among CPGs. Sensitivity analyses testing the robustness were conducted by excluding recommendation statements that were described as insufficient evidence, excluding single recommendation sources, and stratifying by importance of recommendations. Results: The analysis included 8 CPGs with a total of 71 reference recommendations, 68 of which had clear recommendations from 2 or more CPGs. Across CPGs, 22 recommendations (32%) were consistent in direction and strength, 18 recommendations (27%) were consistent in direction but inconsistent in strength, and 28 recommendations (41%) were inconsistent in direction. The rate of consistency was lower in secondary analyses. When insufficient evidence ratings were excluded, there was still substantial inconsistency, and a leave-one-out sensitivity analysis suggested the inconsistency could not be attributed to any single recommendation source. Inconsistency in direction was more common for recommendations deemed to be of lower importance (11 of 20 recommendations [55%]), but 17 of 48 high-importance recommendations (35%) had inconsistency in direction. Conclusions and Relevance: Hypertension is a common chronic condition with widespread expectations surrounding guideline-based care, yet CPGs have a high rate of inconsistency. Further investigations should determine the reasons for inconsistency, the implications for recommendation development, and the role of synthesis across recommendations for optimal guidance of clinical care.

20-HETE mediates ozone-induced, neutrophil-independent airway hyper-responsiveness in mice.

BACKGROUND: Ozone, a pollutant known to induce airway hyper-responsiveness (AHR), increases morbidity and mortality in patients with obstructive airway diseases and asthma. We postulate oxidized lipids mediate in vivo ozone-induced AHR in murine airways. METHODOLOGY/PRINCIPAL FINDINGS: Male BALB/c mice were exposed to ozone (3 or 6 ppm) or filtered air (controls) for 2 h. Precision cut lung slices (PCLS; 250 microm thickness) containing an intrapulmonary airway ( approximately 0.01 mm(2) lumen area) were prepared immediately after exposure or 16 h later. After 24 h, airways were contracted to carbachol (CCh). Log EC(50) and E(max) values were then calculated by measuring the airway lumen area with respect to baseline. In parallel studies, dexamethasone (2.5 mg/kg), or 1-aminobenzotriazol (ABT) (50 mg/kg) were given intraperitoneal injection to naïve mice 18 h prior to ozone exposure. Indomethacin (10 mg/kg) was administered 2 h prior. Cell counts, cytokine levels and liquid chromatography-mass spectrometry (LC-MS) for lipid analysis were assessed in bronchoalveolar lavage (BAL) fluid from ozone exposed and control mice. Ozone acutely induced AHR to CCh. Dexamethasone or indomethacin had little effect on the ozone-induced AHR; while, ABT, a cytochrome P450 inhibitor, markedly attenuated airway sensitivity. BAL fluid from ozone exposed animals, which did not contain an increase in neutrophils or interleukin (IL)-6 levels, increased airway sensitivity following in vitro incubation with a naïve PCLS. In parallel, significant increases in oxidized lipids were also identified using LC-MS with increases of 20-HETE that were decreased following ABT treatment. CONCLUSIONS/SIGNIFICANCE: These data show that ozone acutely induces AHR to CCh independent of inflammation and is insensitive to steroid treatment or cyclooxygenase (COX) inhibition. BAL fluid from ozone exposed mice mimicked the effects of in vivo ozone exposure that were associated with marked increases in oxidized lipids. 20-HETE plays a pivotal role in mediating acute ozone-induced AHR.

Inhibition of myristoylated alanine-rich C kinase substrate (MARCKS) protein inhibits ozone-induced airway neutrophilia and inflammation.

Evidence suggests inhibition of leukocyte trafficking mitigates, in part, ozone-induced inflammation. In the present study, the authors postulated that inhibition of myristoylated alanine-rich C kinase substrate (MARCKS), an 82-kDa protein with multiple biological roles, could inhibit ozone-induced leukocyte trafficking and cytokine secretions. BALB/c mice (n = 5/cohort) were exposed to ozone (100 ppb) or forced air (FA) for 4 hours. MARCKS-inhibiting peptides, MANS, BIO-11000, BIO-11006, or scrambled control peptide RNS, were intratracheally administered prior to ozone exposure. Ozone selectively enhanced bronchoalveolar lavage (BAL) levels of killer cells (KCs; 6 +/- 0.9-fold), interleukin-6 (IL-6; 12.7 +/- 1.9-fold), and tumor necrosis factor (TNF; 2.1 +/- 0.5-fold) as compared to cohorts exposed to FA. Additionally, ozone increased BAL neutrophils by 21% +/- 2% with no significant (P > .05) changes in other cell types. MANS, BIO-11000, and BIO-11006 significantly reduced ozone-induced KC secretion by 66% +/- 14%, 47% +/- 15%, and 71.1% +/- 14%, and IL-6 secretion by 69% +/- 12%, 40% +/- 7%, and 86.1% +/- 11%, respectively. Ozone-mediated increases in BAL neutrophils were reduced by MANS (86% +/- 7%) and BIO-11006 (84% +/- 2.5%), but not BIO-11000. These studies identify for the first time the novel potential of MARCKS protein inhibitors in abrogating ozone-induced increases in neutrophils, cytokines, and chemokines in BAL fluid. BIO-11006 is being developed as a treatment for chronic obstructive pulmonary disorder (COPD) and is currently being evaluated in a phase 2 clinical study.