Dysregulated Interferon Response Underlying Severe COVID-19

Innate immune interferons (IFNs), including type I and III IFNs, constitute critical antiviral mechanisms. Recent studies reveal that IFN dysregulation is key to determine COVID-19 pathogenesis. Effective IFN stimulation or prophylactic administration of IFNs at the early stage prior to severe COVID-19 may elicit an autonomous antiviral state, restrict the virus infection, and prevent COVID-19 progression. Inborn genetic flaws and autoreactive antibodies that block IFN response have been significantly associated with about 14% of patients with life-threatening COVID-19 pneumonia. In most severe COVID-19 patients without genetic errors in IFN-relevant gene loci, IFN dysregulation is progressively worsened and associated with the situation of pro-inflammation and immunopathy, which is prone to autoimmunity. In addition, the high correlation of severe COVID-19 with seniority, males, and individuals with pre-existing comorbidities will be plausibly explained by the coincidence of IFN aberrance in these situations. Collectively, current studies call for a better understanding of the IFN response regarding the spatiotemporal determination and subtype-specificity against SARS-CoV-2 infections, which are warranted to devise IFN-related prophylactics and therapies.     

Significant clinical impact and prognostic stratification provided by FDG-PET in the staging of oesophageal cancer

Purpose To evaluate the clinical impact of FDG-PET in staging oesophageal cancer and whether this information improves prognostic stratification. Methods Impact was based on comparison of a prospectively recorded pre-PET plan with post-PET treatment in 68 consecutive patients undergoing primary staging. Survival was analysed using the Kaplan-Meier product limit method and the Cox proportional hazards regression model. Results FDG-PET findings impacted on the management of 27/68 patients (40%): in 12 therapy was changed from curative to palliative and in three from palliative to curative, while in 12 other patients there was a change in the treatment modality or delivery but not in the treatment intent. The median survival was 21 months, with post-PET stage and treatment intent both strongly associated with survival (p<0.001). Conventional stage was not able to clearly stratify this population. Conclusion The use of FDG-PET for primary staging of oesophageal cancer changed the clinical management of more than one-third of patients and provided superior prognostic stratification compared with conventional investigations.     

Integration of Improvement and Implementation Science in Practice-Based Research Networks: a Longitudinal,Comparative Case Study

BackgroundImplementation science (IS) and quality improvement (QI) inhabit distinct areas of scholarly literature, but are often blended in practice. Because practice-based research networks (PBRNs) draw from both traditions, their experience could inform opportunities for strategic IS-QI alignment.ObjectiveTo systematically examine IS, QI, and IS/QI projects conducted within a PBRN over time to identify similarities, differences, and synergies.DesignLongitudinal, comparative case study of projects conducted in the Oregon Rural Practice-based Research Network (ORPRN) from January 2007 to January 2019.ApproachWe reviewed documents and conducted staff interviews. We classified projects as IS, QI, IS/QI, or other using established criteria. We abstracted project details (e.g., objective, setting, theoretical framework) and used qualitative synthesis to compare projects by classification and to identify the contributions of IS and QI within the same project.Key ResultsAlmost 30% (26/99) of ORPRN’s projects included IS or QI elements; 54% (14/26) were classified as IS/QI. All 26 projects used an evidence-based intervention and shared many similarities in relation to objective and setting. Over half of the IS and IS/QI projects used randomized designs and theoretical frameworks, while no QI projects did. Projects displayed an upward trend in complexity over time. Project used a similar number of practice change strategies; however, projects classified as IS predominantly employed education/training while all IS/QI and most QI projects used practice facilitation. Projects including IS/QI elements demonstrated the following contributions: QI provides the mechanism by which the principles of IS are operationalized in order to support local practice change and IS in turn provides theories to inform implementation and evaluation to produce generalizable knowledge.ConclusionsOur review of projects conducted over a 12-year period in one PBRN demonstrates key synergies for IS and QI. Strategic alignment of IS/QI within projects may help improve care quality and bridge the research-practice gap.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-06610-1.KEY WORDS: pragmatic research, implementation science, quality improvement, primary care, rural health services, practice-based research     

Using the Six Sigma Process to Implement the Centers for Disease Control and Prevention Guideline for Hand Hygiene in 4 Intensive Care Units

BACKGROUND: The Centers for Disease Control and Prevention (CDC) Guideline for Hand Hygiene in Health Care Settings was issued in 2002. In 2003, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) established complying with the CDC Guideline as a National Patient Safety Goal for 2004. This goal has been maintained through 2006. The CDC's emphasis on the use of alcohol-based hand rubs (ABHRs) rather than soap and water was an opportunity to improve compliance, but the Guideline contained over 40 specific recommendations to implement.
OBJECTIVE: To use the Six Sigma process to examine hand hygiene practices and increase compliance with the CDC hand hygiene recommendations required by JCAHO.
DESIGN: Six Sigma Project with pre-post design.
PARTICIPANTS: Physicians, nurses, and other staff working in 4 intensive care units at 3 hospitals.
MEASUREMENTS: Observed compliance with 10 required hand hygiene practices, mass of ABHR used per month per 100 patient-days, and staff attitudes and perceptions regarding hand hygiene reported by questionnaire.
RESULTS: Observed compliance increased from 47% to 80%, based on over 4,000 total observations. The mass of ABHR used per 100 patient-days in 3 intensive care units (ICUs) increased by 97%, 94%, and 70%; increases were sustained for 9 months. Self-reported compliance using the questionnaire did not change. Staff reported increased use of ABHR and increased satisfaction with hand hygiene practices and products.
CONCLUSIONS: The Six Sigma process was effective for organizing the knowledge, opinions, and actions of a group of professionals to implement the CDC's evidence-based hand hygiene practices in 4 ICUs. Several tools were developed for widespread use.     

Percutaneous balloon pulmonic valvuloplasty following treated endocarditis in a patient with congenital pulmonary valve stenosis

A 36-year-old woman with congenital pulmonary valve stenosis developed the rare complication of endocarditis of the valve. After successful sterilization of the valve, the patient underwent percutaneous balloon pulmonic valvuloplasty at a later date. The procedure successfully reduced the peak pulmonary valve gradient from 94 to 45 mm Hg. Percutaneous balloon valvuloplasty is the procedure of choice for treatment of congenital pulmonary valvular stenosis, even in the unusual patient who has healed endocarditis of the pulmonary valve.