Causes, Diagnostic Testing, and Treatments Related to Clinical Deterioration Events among High-Risk Ward Patients.

OBJECTIVE: Timely intervention for clinically deteriorating ward patients requires that care teams accurately diagnose and treat their underlying medical conditions. However, the most common diagnoses leading to deterioration and the relevant therapies provided are poorly characterized. Therefore, we aimed to determine the diagnoses responsible for clinical deterioration, the relevant diagnostic tests ordered, and the treatments administered among high-risk ward patients using manual chart review. DESIGN: Multicenter retrospective observational study. SETTING: Inpatient medical-surgical wards at four health systems from 2006-2020 PATIENTS: Randomly selected patients (1,000 from each health system) with clinical deterioration, defined by reaching the 95th percentile of a validated early warning score, electronic Cardiac Arrest Risk Triage (eCART), were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical deterioration was confirmed by a trained reviewer or marked as a false alarm if no deterioration occurred for each patient. For true deterioration events, the condition causing deterioration, relevant diagnostic tests ordered, and treatments provided were collected. Of the 4,000 included patients, 2,484 (62%) had clinical deterioration confirmed by chart review. Sepsis was the most common cause of deterioration (41%; n=1,021), followed by arrhythmia (19%; n=473), while liver failure had the highest in-hospital mortality (41%). The most common diagnostic tests ordered were complete blood counts (47% of events), followed by chest x-rays (42%), and cultures (40%), while the most common medication orders were antimicrobials (46%), followed by fluid boluses (34%), and antiarrhythmics (19%). CONCLUSIONS: We found that sepsis was the most common cause of deterioration, while liver failure had the highest mortality. Complete blood counts and chest x-rays were the most common diagnostic tests ordered, and antimicrobials and fluid boluses were the most common medication interventions. These results provide important insights for clinical decision-making at the bedside, training of rapid response teams, and the development of institutional treatment pathways for clinical deterioration. KEY POINTS: Question: What are the most common diagnoses, diagnostic test orders, and treatments for ward patients experiencing clinical deterioration? Findings: In manual chart review of 2,484 encounters with deterioration across four health systems, we found that sepsis was the most common cause of clinical deterioration, followed by arrythmias, while liver failure had the highest mortality. Complete blood counts and chest x-rays were the most common diagnostic test orders, while antimicrobials and fluid boluses were the most common treatments. Meaning: Our results provide new insights into clinical deterioration events, which can inform institutional treatment pathways, rapid response team training, and patient care.

A Mixed-Methods Study of Veterans Affairs Providers' Experiences Communicating With Patients About the Affordable Care Act.

OBJECTIVE: The provisions under the Affordable Care Act (ACA) can potentially increase insurance options for Veterans. Veterans must be informed about their options, and potential benefits and challenges associated with use of multiple health care systems. This study aimed to assess VA providers' perceptions of how they contributed to Veterans' health care decision-making within the health care context established by the ACA. MATERIALS AND METHODS: A mixed-methods approach including an online survey and semi-structured interviews was used to assess the experiences of health care providers (e.g., physicians, nurses, and social workers) communicating with Veterans about the ACA. Closed-ended survey questions were analyzed using descriptive statistics. Qualitative analysis of open-ended responses to the survey and semi-structured interview entailed thematic analysis, which involved identifying themes and patterns within and across participants until reaching saturation. RESULTS: A total of 251 providers completed the survey (20% response rate), and 26 providers completed a semi-structured interview (23% participation rate). Most providers (75.3%) reported being only "a little" or "somewhat" knowledgeable about the overall provisions of the ACA, and 90.8% of providers reported needing more information about the ACA. Key themes that emerged from the qualitative analyses included a variety of issues related to the ACA. According to providers, Veterans raised concerns about: signing up for the ACA, retaining VA benefits, knowledge about VA benefits and the ACA, understanding implications of insurance coverage through the ACA, and affordability of the ACA. Providers expressed the need for provider and patient educational resources. CONCLUSION: Our findings suggest that Veterans and their providers encounter challenges comprehending recent policy changes and navigating ongoing dual health care use. According to providers, Veterans' knowledge about the ACA can affect their ability to make informed health care decisions. Equipping patients and providers with more information about the ACA, and promoting communication between patients and providers may foster shared decision-making processes with regard to health care and treatment options. Strategies to improve knowledge transfer and patient-provider communication about policy changes warrant further investigation.

Medication acquisition by veterans dually eligible for Veterans Affairs and Medicare Part D pharmacy benefits.

PURPOSE: The patterns of medication acquisition for veterans dually eligible for pharmacy benefits from the Department of Veterans Affairs (VA) and Medicare Part D-reimbursed pharmacies were examined. METHODS: The characteristics of veterans who used pharmacies reimbursed by (1) VA only, (2) both VA and Part D-reimbursed, and (3) Part D-reimbursed only pharmacies in 2009 were compared and their medication types and sources examined. Pharmacy usage was measured as the number of 30-day medication supplies and the number of different drug classes that veterans received from VA and Part D-reimbursed pharmacies. Chi-square testing and analysis of variance were used to compare unadjusted patient characteristics and healthcare utilization. RESULTS: A total of 145,899 veterans with any VA or Part D-reimbursed pharmacy use were included in the study: 69.6% used VA pharmacies only, 9.9% used VA and Part D-reimbursed pharmacies, and 20.5% used Part D-reimbursed pharmacies only. Veterans who lived in rural areas, were non-Black, had VA medication copayments, or were dual or Medicare-only outpatient users were more likely to be dual or Part D-reimbursed only pharmacy users (p < 0.001). Dual pharmacy users received more 30-day supplies than did the other two pharmacy-use groups (p < 0.001). CONCLUSION: Nearly one third of VA users received medications from Part D-reimbursed pharmacies, either alone or together with VA pharmacies. Among dual pharmacy users, over half received medications from the same drug class from both VA and Part D-reimbursed pharmacies for which the days' supplies overlapped by more than seven days.

CCL22 to Activate Treg Migration and Suppress Depigmentation in Vitiligo.

In vitiligo, gradual cutaneous depigmentation and cytotoxic T-cell activity against melanocytes are accompanied by a paucity of regulatory T cells (Tregs) in vitiligo patient skin, indicating that autoimmune responses are not adequately held in check. Thus, we sought a means to repopulate patient skin with Tregs. We hypothesized that enhanced expression of CCL22 can promote Treg skin homing to suppress depigmentation. The mouse Ccl22 gene was cloned into an expression vector and resulting DNA was used for gene gun treatment. Two spontaneous depigmentation models with different kinetics of melanocyte loss were utilized, expressing tyrosinase-reactive and gp100-reactive TCR transgenes. Mice were subjected to five gene gun treatments 6 days apart, scanned for depigmentation weekly thereafter, and monitored for activation and proliferation of relevant T cells and for Treg infiltration to the skin. Significantly reduced depigmentation 2 weeks after treatment was accompanied by a markedly increased abundance of Tregs in the skin at the expense of melanocyte-reactive, TCR transgenic T cells, as well as by reduced proliferation and reduced IFN-γ production in response to cognate peptide. Continued treatment may be necessary for sustained, local immunosuppression. These findings suggest that topical CCL22 may be used for the treatment of vitiligo.

New approaches to the treatment of dense deposit disease.

The development of clinical treatment protocols usually relies on evidence-based guidelines that focus on randomized, controlled trials. For rare renal diseases, such stringent requirements can represent a significant challenge. Dense deposit disease (DDD; also known as membranoproliferative glomerulonephritis type II) is a prototypical rare disease. It affects only two to three people per million and leads to renal failure within 10 yr in 50% of affected children. On the basis of pathophysiology, this article presents a diagnostic and treatment algorithm for patients with DDD. Diagnostic tests should assess the alternative pathway of complement for abnormalities. Treatment options include aggressive BP control and reduction of proteinuria, and on the basis of pathophysiology, animal data, and human studies, plasma infusion or exchange, rituximab, sulodexide, and eculizumab are additional options. Criteria for treatment success should be prevention of progression as determined by maintenance or improvement in renal function. A secondary criterion should be normalization of activity levels of the alternative complement pathway as measured by C3/C3d ratios and C3NeF levels. Outcomes should be reported to a central repository that is now accessible to all clinicians. As the understanding of DDD increases, novel therapies should be integrated into existing protocols for DDD and evaluated using an open-label Bayesian study design.

Membranoproliferative glomerulonephritis type II (dense deposit disease): an update.

Membranoproliferative glomerulonephritis type II (MPGN II) is a rare disease characterized by the deposition of abnormal electron-dense material within the glomerular basement membrane of the kidney and often within Bruch's membrane in the eye. The diagnosis is made in most patients between the ages of 5 and 15 yr, and within 10 yr, approximately half progress to end-stage renal disease, occasionally with the late comorbidity of visual impairment. The pathophysiologic basis of MPGN II is associated with the uncontrolled systemic activation of the alternative pathway (AP) of the complement cascade. In most patients, loss of complement regulation is caused by C3 nephritic factor, an autoantibody directed against the C3 convertase of the AP, but in some patients, mutations in the factor H gene have been identified. For the latter patients, plasma replacement therapy prevents renal failure, but for the majority of patients, there is no proven effective treatment. The disease recurs in virtually all renal allografts, and a high percentage of these ultimately fail. The development of molecular diagnostic tools and new therapies directed at controlling the AP of the complement cascade either locally in the kidney or at the systemic level may lead to effective treatments for MPGN II.