COVID-19 Severity and Mortality in Veterans with Chronic Lung Disease.

Rationale: Chronic lung diseases (CLDs) have been variably associated with a risk for more severe manifestations and death with coronavirus disease (COVID-19). Objectives: To determine the risk overall and by type of CLD for severity of COVID-19 outcomes in a U.S. national cohort. Methods: Using data from the Veterans Health Administration, we determined the risk associated with CLDs, including chronic obstructive pulmonary disease (COPD) (mild or severe), asthma (mild, active, or severe), idiopathic pulmonary fibrosis (IPF), sarcoidosis, and other interstitial lung diseases (ILDs) for outcomes among veterans with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive tests between March 1, 2020 and April 30, 2021. We used multinomial regression to estimate risk of four mutually exclusive COVID-19 outcomes within 30 days: outpatient management, hospitalization, hospitalization with indicators of critical illness, or death. We calculated the overall proportion with each outcome, the absolute risk difference, and risk ratios for each outcome between those with and without CLD. We also describe clinical and laboratory abnormalities by CLD in those hospitalized. Results: We included 208,283 veterans with COVID-19; 35,587 (17%) had CLD. Compared with no CLD, veterans with CLD were older and had more comorbidities. Hospitalized veterans with CLD were more likely to have low temperature, mean arterial pressure, oxygen saturation, and leukopenia and thrombocytopenia and were more likely to receive oxygen, mechanical ventilation, and vasopressors. Veterans with CLD were significantly less likely to have mild COVID-19 (-4.5%; adjusted risk ratio [aRR], 0.94; 95% confidence interval [CI], 0.94-0.95), and more likely to have a moderate (+2.5%; aRR, 1.21; 95% CI, 1.18-1.24), critical (+1.4%; aRR, 1.38; 95% CI, 1.32-1.45), or fatal (+0.7%; aRR, 1.15; 95% CI, 1.10-1.20) outcome. IPF was most strongly associated with COVID-19 severity, especially mortality (+3.2%; aRR, 1.69; 95% CI, 1.46-1.96), followed by other ILDs and COPD, whereas asthma was less likely to be associated with severity of COVID-19. In veterans younger than age 65 years, worse COVID-19 outcomes were generally more likely with IPF, sarcoidosis, and other ILDs. Conclusions: Veterans who had CLD, particularly IPF, other ILDs, and COPD, had an increased probability of more severe 30-day outcomes with COVID-19. These results provide insight into the absolute and relative risk of different CLDs with severity of COVID-19 outcomes and can help inform considerations of healthcare utilization and prognosis. Observational clinical epidemiology study registered with www.clinicaltrials.gov (NCT04628039).

Association of Tubular Solute Clearance with Symptom Burden in Incident Peritoneal Dialysis.

BACKGROUND AND OBJECTIVES: Residual kidney function is important to the health and wellbeing of patients with ESKD. We tested whether the kidney clearances of proximal tubular secretory solutes are associated with burden of uremic and heart failure symptoms among patients on peritoneal dialysis with residual kidney function. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We enrolled 29 patients on incident peritoneal dialysis with residual urine output >250 ml daily. We used targeted liquid chromatography-mass spectrometry to quantify plasma, 24-hour urine, and peritoneal dialysate concentrations of ten tubular secretory solutes. We calculated the kidney and peritoneal dialysis clearances of each secretory solute, creatinine, and urea, and we estimated a composite kidney and peritoneal secretion score. We assessed for uremic symptoms using the Dialysis Symptom Index and heart failure-related symptoms using the Kansas City Cardiomyopathy Questionnaire. We used linear regression to determine associations of composite secretory solute clearances and GFRurea+Cr with Dialysis Symptom Index symptom score and Kansas City Cardiomyopathy Questionnaire summary score. RESULTS: Mean residual kidney clearances of creatinine and urea were 8±5 and 9±6 ml/min per 1.73 m2, respectively, and mean GFRurea+Cr was 8±5 ml/min per 1.73 m2. The residual kidney clearances of most secretory solutes were considerably higher than creatinine and urea clearance, and also, they were higher than their respective peritoneal dialysis clearances. After adjustments for age and sex, each SD higher composite kidney secretion score was associated with an 11-point lower Dialysis Symptom Index score (95% confidence interval, -20 to -1; P=0.03) and a 12-point higher Kansas City Cardiomyopathy Questionnaire score (95% confidence interval, 0.5- to 23-point higher score; P=0.04). Composite peritoneal dialysis secretion score was not associated with either symptom assessment. CONCLUSIONS: Residual kidney clearances of secretory solutes are higher than peritoneal dialysis clearances. Kidney clearances of secretory solutes are associated with patient-reported uremic and heart failure-related symptoms.

A wearable artificial kidney for patients with end-stage renal disease.

BACKGROUND: Stationary hemodialysis machines hinder mobility and limit activities of daily life during dialysis treatments. New hemodialysis technologies are needed to improve patient autonomy and enhance quality of life. METHODS: We conducted a FDA-approved human trial of a wearable artificial kidney, a miniaturized, wearable hemodialysis machine, based on dialysate-regenerating sorbent technology. We aimed to determine the efficacy of the wearable artificial kidney in achieving solute, electrolyte, and volume homeostasis in up to 10 subjects over 24 hours. RESULTS: During the study, all subjects remained hemodynamically stable, and there were no serious adverse events. Serum electrolytes and hemoglobin remained stable over the treatment period for all subjects. Fluid removal was consistent with prescribed ultrafiltration rates. Mean blood flow was 42 ± 24 ml/min, and mean dialysate flow was 43 ± 20 ml/min. Mean urea, creatinine, and phosphorus clearances over 24 hours were 17 ± 10, 16 ± 8, and 15 ± 9 ml/min, respectively. Mean ß2-microglobulin clearance was 5 ± 4 ml/min. Of 7 enrolled subjects, 5 completed the planned 24 hours of study treatment. The trial was stopped after the seventh subject due to device-related technical problems, including excessive carbon dioxide bubbles in the dialysate circuit and variable blood and dialysate flows. CONCLUSION: Treatment with the wearable artificial kidney was well tolerated and resulted in effective uremic solute clearance and maintenance of electrolyte and fluid homeostasis. These results serve as proof of concept that, after redesign to overcome observed technical problems, a wearable artificial kidney can be developed as a viable novel alternative dialysis technology. TRIAL REGISTRATION: ClinicalTrials.gov NCT02280005. FUNDING: The Wearable Artificial Kidney Foundation and Blood Purification Technologies Inc.

Use of the national surgical quality improvement program to reduce surgical mortality: implementation of intensive preoperative screening and intervention.

The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) data at our institution indicated that surgical mortality was significantly higher than expected. This study examines the effect of implementation of a strict, intensive preoperative screening and intervention process on postoperative mortality at our institution, as measured by the NSQIP. Carilion Roanoke Memorial Hospital (CRMH) is a 763-bed tertiary care hospital serving a population of one million people in southwest Virginia. Data were collected for NSQIP at CRMH from July 2007 to December 2012. In January 2010, a new preoperative process was implemented to include risk assessment and intervention for hypertension, cardiac disease, pulmonary disease, diabetes, renal disease, and obstructive sleep apnea. Before initiation of our preoperative program (July 2007 to January 2010), odds ratios (ORs) for 30-day mortality in general and vascular cases were significantly higher than expected (1.40, 1.43, 1.58, and 1.56 in successive reporting periods). Beginning with the first report after implementation of the preoperative screening program, CRMH showed a progressively decreasing OR for overall 30-day mortality (1.26, 1.19, 1.14, 0.86, 0.82, 0.84, 0.89) with similar reductions in both general (0.92) and vascular (0.92) surgery. The implementation of an intensive preoperative screening and intervention process in our institution was accompanied by a significant decrease in the 30-day mortality for general surgery and vascular procedures, as measured by the NSQIP.

Control of simultaneous outbreaks of carbapenemase-producing enterobacteriaceae and extensively drug-resistant Acinetobacter baumannii infection in an intensive care unit using interventions promoted in the Centers for Disease Control and Prevention 2012 carbapenemase-resistant Enterobacteriaceae Toolkit.

OBJECTIVE: We describe the efficacy of enhanced infection control measures, including those recommended in the Centers for Disease Control and Prevention's 2012 carbapenem-resistant Enterobacteriaceae (CRE) toolkit, to control concurrent outbreaks of carbapenemase-producing Enterobacteriaceae (CPE) and extensively drug-resistant Acinetobacter baumannii (XDR-AB). DESIGN: Before-after intervention study. SETTING: Fifteen-bed surgical trauma intensive care unit (ICU). METHODS: We investigated the impact of enhanced infection control measures in response to clusters of CPE and XDR-AB infections in an ICU from April 2009 to March 2010. Polymerase chain reaction was used to detect the presence of blaKPC and resistance plasmids in CRE. Pulsed-field gel electrophoresis was performed to assess XDR-AB clonality. Enhanced infection-control measures were implemented in response to ongoing transmission of CPE and a new outbreak of XDR-AB. Efficacy was evaluated by comparing the incidence rate (IR) of CPE and XDR-AB before and after the implementation of these measures. RESULTS: The IR of CPE for the 12 months before the implementation of enhanced measures was 7.77 cases per 1,000 patient-days, whereas the IR of XDR-AB for the 3 months before implementation was 6.79 cases per 1,000 patient-days. All examined CPE shared endemic blaKPC resistance plasmids, and 6 of the 7 XDR-AB isolates were clonal. Following institution of enhanced infection control measures, the CPE IR decreased to 1.22 cases per 1,000 patient-days (P = .001), and no more cases of XDR-AB were identified. CONCLUSIONS: Use of infection control measures described in the Centers for Disease Control and Prevention's 2012 CRE toolkit was associated with a reduction in the IR of CPE and an interruption in XDR-AB transmission.

Physical activity and change in estimated GFR among persons with CKD.

Physical activity may counteract metabolic disturbances that promote the progression of CKD. To address this concept, we performed a longitudinal cohort study of 256 participants in the Seattle Kidney Study, a clinic-based study of CKD. Participants with an estimated GFR (eGFR) of 15-59 ml/min per 1.73 m(2) at baseline were eligible for the study. Physical activity was quantified using the Four-Week Physical Activity History Questionnaire. We used generalized estimating equations to test associations of physical activity with change in eGFR determined by longitudinal measurements of serum cystatin C. Mean baseline eGFR was 42 ml/min per 1.73 m(2). During a median 3.7 years of follow-up, the mean change in eGFRcystatin C was -7.6% per year (interquartile range, -16.8%, 4.9% per year). Participants who reported >150 minutes of physical activity per week had the lowest rate of eGFRcystatin C loss (mean -6.2% per year compared with -9.6% per year among inactive participants). In adjusted analyses, each 60-minute increment in weekly physical activity duration associated with a 0.5% slower decline per year in eGFR (95% confidence interval, 0.02 to 0.98; P=0.04). Results were similar in sensitivity analyses restricted to participants without cardiovascular disease or diabetes, or to participants with moderate/high physical function. After adjustment for eGFR at the time of questionnaire completion, physical activity did not associate with the incidence of ESRD (n=34 events). In summary, higher physical activity levels associated with slower rates of eGFR loss in persons with established CKD.

Community-associated and healthcare-associated methicillin-resistant Staphylococcus aureus virulence toward Caenorhabditis elegans compared.

Community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged as major human pathogens. CA-MRSA virulence appears to be distinct from healthcare-associated (HA) MRSA with several factors [α-hemolysin (Hla), Panton-Valentine leukocidin (PVL), α-type phenol soluble modulins (PSMα) and SCCmec IV] postulated to enhance virulence or fitness. Using the Caenorhabditis elegans infection model, we compared the virulence of clinical and laboratory isolates of CA-MRSA and HA-MRSA and explored the contribution of CA-MRSA associated virulence factors to nematode killing. All CA-MRSA strains were highly pathogenic to nematodes, while HA-MRSA strains demonstrated variable nematode killing. Nematode killing by isogenic mutants of hla or the loci for PVL, PSMα, PSMß, PSMδ or SCCmec IV was not different than the parental strains. These results demonstrate that CA-MRSA is highly virulent, shows some strains of HA-MRSA are equally virulent toward nematodes and suggests CA-MRSA virulence in C. elegans is not linked to a single virulence factor.