Underuse of Antiviral Drugs to Prevent Progression to Severe COVID-19 - Veterans Health Administration, March-September 2022.

Antiviral drugs reduce the rate of progression to severe COVID-19 when given to patients with mild-to-moderate disease within 5 days of symptom onset. Despite being recommended for patients at high risk for progression to severe COVID-19 because of age or chronic conditions, reported antiviral use among the general adult population has been ≤35%. To ascertain reasons for underuse of antiviral medications to prevent severe COVID-19 and propose interventions accordingly, a detailed review was conducted of 110 Veterans Health Administration patients with mild-to-moderate infection at high risk for progression because of underlying conditions (organ transplantation or hematologic malignancies) who did not receive an antiviral drug. Among these 110 patients, all of whom had received COVID-19 vaccine, 22 (20.0%) were offered treatment but declined, and 88 (80.0%) were not offered treatment. Among the 88 patients not offered treatment, provider reasons included symptom duration of >5 days (22.7%), concern about possible drug interactions (5.7%), or absence of symptoms (22.7%); however, among nearly one half (43 of 88; 48.9%) of these patients, no reason other than mild symptoms was given. Among 24 (55.8%) of those 43 patients, follow-up was limited to telephone calls to report test results and inquire about symptom evolution, with no documentation of treatment being offered. These findings suggest that education of patients, providers, and medical personnel tasked with follow-up calls, combined with advance planning in the event of a positive test result, might improve the rate of recommended antiviral medication use to prevent severe COVID-19-associated illness, including death.

Risk of severe coronavirus disease 2019 despite vaccination in patients requiring treatment with immune-suppressive drugs: A nationwide cohort study of US Veterans.

BACKGROUND: Patients taking immune-suppressive drugs are at increased risk of severe coronavirus disease 2019 (COVID-19), not fully ameliorated by vaccination. We assessed the contributions of clinical and demographic factors to the risk of severe disease despite vaccination in patients taking immune-suppressive medications for solid organ transplantation (SOT), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), or psoriasis. METHODS: Veterans Health Administration electronic health records were used to identify patients diagnosed with RA, IBD, psoriasis, or SOT who had been vaccinated against severe acute respiratory syndrome coronavirus 2, were subsequently infected, and had received immune-suppressive drugs within 3 months before infection. The association of severe (defined as hypoxemia, mechanical ventilation, dexamethasone use, or death) versus non-severe COVID-19 with the use of immune-suppressive and antiviral drugs and clinical covariates was assessed by multivariable logistic regression. RESULTS: Severe COVID-19 was more common in patients with SOT (230/1011, 22.7%) than RA (173/1355, 12.8%), IBD (51/742, 6.9%), or psoriasis (82/1125, 7.3%). Age was strongly associated with severe COVID-19, adjusted odds ratio (aOR) of 1.04 (CI 1.03-1.05) per year. Comorbidities indicating chronic brain, heart, lung, or kidney damage were also associated with severity, aOR 1.35-2.38. The use of glucocorticoids was associated with increased risk (aOR 1.66, CI 1.39-2.18). Treatment with antivirals was associated with reduced severity, for example, aOR 0.28 (CI 0.13-0.62) for nirmatrelvir/ritonavir. CONCLUSION: The risk of severe COVID-19 despite vaccination is substantial in patients taking immune-suppressive drugs, more so in patients with SOT than in patients with inflammatory diseases. Age and severe comorbidities contribute to risk, as in the general population. Oral antivirals were very beneficial but not widely used.

Improving COVID-19 Disease Severity Surveillance Measures: Statewide Implementation Experience.

Measurement of the burden of COVID-19 on U.S. hospitals has been an important element of the public health response to the pandemic. However, because of variation in testing density and policies, the metric is not standardized across facilities. Two types of burdens exist, one related to the infection control measures that patients who test positive for SARS-CoV-2 require and one from the care of severely ill patients receiving treatment of COVID-19. With rising population immunity from vaccination and infection, as well as the availability of therapeutics, severity of illness has declined. Prior research showed that dexamethasone administration was highly correlated with other disease severity metrics and sensitive to the changing epidemiology associated with the emergence of immune-evasive variants.On 10 January 2022, the Massachusetts Department of Public Health began requiring hospitals to expand surveillance to include reports of both the total number of "COVID-19 hospitalizations" daily and the number of inpatients who received dexamethasone at any point during their hospital stay. All 68 acute care hospitals in Massachusetts submitted COVID-19 hospitalization and dexamethasone data daily to the Massachusetts Department of Public Health over a 1-year period. A total of 44 196 COVID-19 hospitalizations were recorded during 10 January 2022 to 9 January 2023, of which 34% were associated with dexamethasone administration. The proportion of patients hospitalized with COVID-19 who had received dexamethasone was 49.6% during the first month of surveillance and decreased to a monthly average of approximately 33% by April 2022, where it has remained since (range, 28.7% to 33%).Adding a single data element to mandated reporting to estimate the frequency of severe COVID-19 in hospitalized patients was feasible and provided actionable information for health authorities and policy makers. Updates to surveillance methods are necessary to match data collection with public health response needs.

Condition-Dependent and Dynamic Impacts of Indoor Masking Policies for Coronavirus Disease 2019 Mitigation: A Nationwide, Interrupted Time-Series Analysis.

BACKGROUND: The effectiveness and sustainability of masking policies as a pandemic control measure remain uncertain. Our aim was to evaluate different masking policy types on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) incidence and to identify factors and conditions impacting effectiveness. METHODS: Nationwide, retrospective cohort study of US counties from 4/4/2020-28/6/2021. Policy impacts were estimated using interrupted time-series models with the masking policy change date (eg, recommended-to-required, no-recommendation-to-recommended, no-recommendation-to-required) modeled as the interruption. The primary outcome was change in SARS-CoV-2 incidence rate during the 12 weeks after the policy change; results were stratified by coronavirus disease 2019 (COVID-19) risk level. A secondary analysis was completed using adult vaccine availability as the policy change. RESULTS: In total, N = 2954 counties were included (2304 recommended-to-required, 535 no-recommendation-to-recommended, 115 no-recommendation-to-required). Overall, indoor mask mandates were associated with 1.96 fewer cases/100 000/week (cumulative reduction of 23.52/100 000 residents during the 12 weeks after policy change). Reductions were driven by communities with critical and extreme COVID-19 risk, where masking mandated policies were associated with an absolute reduction of 5 to 13.2 cases/100 000 residents/week (cumulative reduction of 60 to 158 cases/100 000 residents over 12 weeks). Impacts in low- and moderate-risk counties were minimal (<1 case/100 000 residents/week). After vaccine availability, mask mandates were not associated with significant reductions at any risk level. CONCLUSIONS: Masking policy had the greatest impact when COVID-19 risk was high and vaccine availability was low. When transmission risk decreases or vaccine availability increases, the impact was not significant regardless of mask policy type. Although often modeled as having a static impact, masking policy effectiveness may be dynamic and condition dependent.

Maintaining the Utility of Coronavirus Disease 2019 Pandemic Severity Surveillance: Evaluation of Trends in Attributable Deaths and Development and Validation of a Measurement Tool.

BACKGROUND: Death within a specified time window following a positive SARS-CoV-2 test is used by some agencies for attributing death to COVID-19. With Omicron variants, widespread immunity, and asymptomatic screening, there is cause to re-evaluate COVID-19 death attribution methods and develop tools to improve case ascertainment. METHODS: All patients who died following microbiologically confirmed SARS-CoV-2 in the Veterans Health Administration (VA) and at Tufts Medical Center (TMC) were identified. Records of selected vaccinated VA patients with positive tests in 2022, and of all TMC patients with positive tests in 2021-2022, were manually reviewed to classify deaths as COVID-19-related (either directly caused by or contributed to), focused on deaths within 30 days. Logistic regression was used to develop and validate a surveillance model for identifying deaths in which COVID-19 was causal or contributory. RESULTS: Among vaccinated VA patients who died ≤30 days after a positive test in January-February 2022, death was COVID-19-related in 103/150 cases (69%) (55% causal, 14% contributory). In June-August 2022, death was COVID-19-related in 70/150 cases (47%) (22% causal, 25% contributory). Similar results were seen among the 71 patients who died at TMC. A model including hypoxemia, remdesivir, and anti-inflammatory drugs had positive and negative predictive values of 0.82-0.95 and 0.64-0.83, respectively. CONCLUSIONS: By mid-2022, "death within 30 days" did not provide an accurate estimate of COVID-19-related death in 2 US healthcare systems with routine admission screening. Hypoxemia and use of antiviral and anti-inflammatory drugs-variables feasible for reporting to public health agencies-would improve classification of death as COVID-19-related.

Arteriovenous Graft Failure in the Veterans Health Administration: Outcome Disparities Associated with Race.

Background Vascular access for ongoing hemodialysis often fails, frequently requiring repeated procedures to maintain vascular patency. While research has shown racial discrepancies in multiple aspects of renal failure treatment, there is poor understanding of how these factors might relate to vascular access maintenance procedures after arteriovenous graft (AVG) placement. Purpose To evaluate racial disparities associated with premature vascular access failure after percutaneous access maintenance procedures following AVG placement using a retrospective national cohort from the Veterans Health Administration (VHA). Materials and Methods All hemodialysis vascular maintenance procedures performed at VHA hospitals between October 2016 and March 2020 were identified. To ensure the sample represented patients who consistently used the VHA, patients without AVG placement within 5 years of their first maintenance procedure were excluded. Access failure was defined as a repeat access maintenance procedure or as hemodialysis catheter placement occurring 1-30 days after the index procedure. Multivariable logistic regression analyses were performed to calculate prevalence ratios (PRs) measuring the association between hemodialysis maintenance failure and African American race compared with all other races. Models controlled for vascular access history, patient socioeconomic status, and procedure and facility characteristics. Results In total, 1950 access maintenance procedures in 995 patients (mean age, 69 years ± 9 [SD], 1870 men) with an AVG created in one of 61 VHA facilities were identified. Most procedures involved African American patients (1169 of 1950, 60%) and patients residing in the South (1002 of 1950, 51%). Premature access failure occurred in 215 of 1950 (11%) procedures. When compared with all other races, African American race was associated with premature access site failure (PR, 1.4; 95% CI: 1.07, 1.43; P = .02). Among the 1057 procedures in 30 facilities with interventional radiology resident training programs, there was no evidence of racial disparity in the outcome (PR, 1.1; P = .63). Conclusion African American race was associated with higher risk-adjusted rates of premature arteriovenous graft failure after dialysis maintenance. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Forman and Davis in this issue.

Depression, worry, and loneliness are associated with subsequent risk of hospitalization for COVID-19: a prospective study.

BACKGROUND: Pre-pandemic psychological distress is associated with increased susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but associations with the coronavirus disease 2019 (COVID-19) severity are not established. The authors examined the associations between distress prior to SARS-CoV-2 infection and subsequent risk of hospitalization. METHODS: Between April 2020 (baseline) and April 2021, we followed 54 781 participants from three ongoing cohorts: Nurses' Health Study II (NHSII), Nurses' Health Study 3 (NHS3), and the Growing Up Today Study (GUTS) who reported no current or prior SARS-CoV-2 infection at baseline. Chronic depression was assessed during 2010-2019. Depression, anxiety, worry about COVID-19, perceived stress, and loneliness were measured at baseline. SARS-CoV-2 infection and hospitalization due to COVID-19 was self-reported. Relative risks (RRs) were calculated by Poisson regression. RESULTS: 3663 participants reported a positive SARS-CoV-2 test (mean age = 55.0 years, standard deviation = 13.8) during follow-up. Among these participants, chronic depression prior to the pandemic [RR = 1.72; 95% confidence interval (CI) 1.20-2.46], and probable depression (RR = 1.81, 95% CI 1.08-3.03), being very worried about COVID-19 (RR = 1.79; 95% CI 1.12-2.86), and loneliness (RR = 1.81, 95% CI 1.02-3.20) reported at baseline were each associated with subsequent COVID-19 hospitalization, adjusting for demographic factors and healthcare worker status. Anxiety and perceived stress were not associated with hospitalization. Depression, worry about COVID-19, and loneliness were as strongly associated with hospitalization as were high cholesterol and hypertension, established risk factors for COVID-19 severity. CONCLUSIONS: Psychological distress may be a risk factor for hospitalization in patients with SARS-CoV-2 infection. Assessment of psychological distress may identify patients at greater risk of hospitalization. Future work should examine whether addressing distress improves physical health outcomes.

Harm reduction stories: leveraging graphic medicine to engage veterans in substance use services within the VA.

BACKGROUND: Harm reduction strategies can decrease morbidity and mortality associated with substance use. Various barriers limit conversation around substance use between clinicians and patients. Graphic medicine techniques can inform and encourage patient-centered conversations about substance use. We describe the co-development of a harm reduction-focused graphic medicine comic that depicts the infectious risks associated with injection drug use and patient-centered approaches to providing education about potential risk mitigation strategies. METHODS: We formed a co-design group of veterans with lived experience with substance use, physicians, health services researchers, and community-based harm reduction leaders. Over the course of ten sessions, the co-design team developed a storyline and key messages, reviewed draft content and worked with a graphic designer to develop a comic incorporating the veterans' input. During each session, co-design leads presented drafts of the comic and invited feedback from the group. The comic was edited and adapted via this iterative process. RESULTS: The comic depicts a fictionalized clinical vignette in which a patient develops an injection-related abscess and presents to their primary care provider. The dialogue highlights key healthcare principles, including patient autonomy and agency, and highlights strategies for safer use, rather than emphasizing abstinence. Feedback from co-design group participants highlights lessons learned during the development process. DISCUSSION: Graphic medicine is ideally suited for a patient-centered curriculum about harm reduction. This project is one of several interventions that will be integrated into VA facilities nationally to support incorporation of harm reduction principles into the care of persons who inject drugs.

Factors associated with the speed and scope of diffusion of COVID-19 therapeutics in a nationwide healthcare setting: a mixed-methods investigation.

BACKGROUND: The global COVID-19 pandemic is an opportunity to evaluate factors associated with high levels of adoption of different therapeutics in a real-world setting. The aim of this nationwide, retrospective cohort study was to evaluate the diffusion and adoption of novel therapeutics with an emerging evidence basis and to identify factors that influenced physicians' treatment decisions. METHODS: Cohort creation: A cohort of Veteran patients with a microbiologically confirmed diagnosis of SARS-CoV2 were identified, and cases were classified by disease severity (outpatient, inpatient with mild and severe disease, intensive care unit ICU]). After classification of disease severity, the proportion of cases (outpatients) and admissions (inpatients) in each category receiving each type of medication were plotted as a function of time. Identification of milestones and guidance changes: Key medications used for the management of COVID-19 milestones in the release of primary research results in various forms (e.g. via press release, preprint or publication in a traditional medical journal), policy events and dates of key guidelines were identified and plotted as a timeline. After a timeline was created, time points were compared to changes in medication use, and factors potentially impacting the magnitude (i.e. proportion of patients who received the treatment) and the speed (i.e. the slope of the change in use) of practice changes were evaluated. RESULTS: Dexamethasone and remdesivir, the first two medications with clinical trial data to support their use, underwent the most rapid, complete and sustained diffusion and adoption; the majority of practice changes occurred after press releases and preprints were available and prior to guideline changes, although some additional uptake occurred following guideline updates. Medications that were not "first in class", that were identified later in the pandemic, and that had higher perceived risk had slower and less complete uptake regardless of the strength and quality of the evidence supporting the intervention. CONCLUSIONS: Our findings suggest that traditional and social media platforms and preprint releases were major catalysts of practice change, particularly prior to the identification of effective treatments. The "first available treatment in class" impact appeared to be the single most important factor determining the speed and scope of diffusion.

Economic Considerations in Infectious Diseases Emergency Response Preparedness: It's All About the Point of View.

Outbreaks and emergence of novel pathogens present a challenge in economic evaluations of prevention strategies, due to unusually high levels of risk aversion and uncertainty. Here, we discuss cost-effectiveness investigations and interpretation of economic analyses in the context of outbreak planning and containment, and outline considerations for providers, administrators, patients, and policy makers for infection emergency preparedness response.

Effectiveness of 3 Versus 6 ft of Physical Distancing for Controlling Spread of Coronavirus Disease 2019 Among Primary and Secondary Students and Staff: A Retrospective, Statewide Cohort Study.

BACKGROUND: National and international guidelines differ about the optimal physical distancing between students for prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission; studies directly comparing the impact of ≥3 versus ≥6 ft of physical distancing policies in school settings are lacking. Thus, our objective was to compare incident cases of SARS-CoV-2 in students and staff in Massachusetts public schools among districts with different physical distancing requirements. State guidance mandates masking for all school staff and for students in grades 2 and higher; the majority of districts required universal masking. METHODS: Community incidence rates of SARS-CoV-2, SARS-CoV-2 cases among students in grades K-12 and staff participating in-person learning, and district infection control plans were linked. Incidence rate ratios (IRRs) for students and staff members in traditional public school districts with ≥3 versus ≥6 ft of physical distancing were estimated using log-binomial regression; models adjusted for community incidence are also reported. RESULTS: Among 251 eligible school districts, 537 336 students and 99 390 staff attended in-person instruction during the 16-week study period, representing 6 400 175 student learning weeks and 1 342 574 staff learning weeks. Student case rates were similar in the 242 districts with ≥3 versus ≥6 ft of physical distancing between students (IRR, 0.891; 95% confidence interval, .594-1.335); results were similar after adjustment for community incidence (adjusted IRR, 0.904; .616-1.325). Cases among school staff in districts with ≥3 versus ≥6 ft of physical distancing were also similar (IRR, 1.015, 95% confidence interval, .754-1.365). CONCLUSIONS: Lower physical distancing requirements can be adopted in school settings with masking mandates without negatively affecting student or staff safety.

What Is the Primary Driver of Preoperative Vancomycin Use? It's Not Methicillin-resistant Staphylococcus aureus-or Allergy.

Factors driving vancomycin surgical prophylaxis are poorly understood. In a national Veterans Affairs cohort with manually validated data, surgical specialty (cardiac, orthopedics) and perception of high facility methicillin-resistant Staphylococcus aureus (MRSA) prevalence-not MRSA colonization-were the primary drivers of prescribing. A ß-lactam allergy was the second most common reason. These data may inform perioperative stewardship.

How Testing Drives Treatment in Asymptomatic Patients: Level of Pyuria Directly Predicts Probability of Antimicrobial Prescribing.

BACKGROUND: Urinalysis is a readily available test often used for screening. Pyuria is a common finding in asymptomatic patients; however, it is unknown how often identification of pyuria in the absence of confirmatory cultures leads to antimicrobial prescribing. The objective of this study was to measure the association between pyuria and antimicrobial initiation during the perioperative period and assess harms versus benefits of treatment. METHODS: A retrospective cohort of preoperative patients within the national healthcare system during the period 1 October 2008-30 September 2013 who had a urinalysis performed during the 30-day preoperative period was created; patients with positive urine cultures were excluded. The primary exposure was pyuria on preoperative urinalysis. The primary outcome was antimicrobial initiation. Secondary outcomes included postoperative surgical site (SSI), urinary tract (UTI), and Clostridioides difficile infections. Trend and logistic regression analyses were performed. RESULTS: Among 41 373 patients, 3617 had pyuria. 887 (24.5%) patients with pyuria received antimicrobials versus 1918 (5.1%) patients without pyuria. As the degree of pyuria increased, the odds of receiving antimicrobials also increased linearly (low, 14.7%; moderate, 24.0%; high pyuria, 37.4%). Preoperative pyuria was associated with postoperative C. difficile infections (aOR, 1.7; 95% CI, 1.2-2.4); risk was higher in patients who received antimicrobials (aOR, 2.4; 1.7-3.4). Pyuria was not associated with SSI but was associated with increases in UTI after orthopedic and vascular procedures; this risk was not mitigated by antimicrobial therapy. CONCLUSIONS: Urine screening during the preoperative period is a low-value intervention that increases antimicrobial exposure but does not improve postoperative outcomes.

Successful treatment of fulminant Clostridioides difficile infection with emergent fecal microbiota transplantation in a patient with acute myeloid leukemia and prolonged, severe neutropenia.

We present a patient with acute myeloid leukemia and prolonged, severe neutropenia who developed fulminant Clostridioides difficile infection refractory to medical therapy and was high-risk for surgical intervention. He was treated with fecal microbiota transplantation (FMT) for life-saving cure. The patient had subsequent clinical improvement, however, developed multidrug-resistant Pseudomonas aeruginosa bacteremia 2 days post-procedure. We describe subsequent investigation of this event that found this bacteremia was not related to the donor stool administered during FMT. This case adds to the literature that FMT could be considered in heavily immunocompromised patients with fulminant Clostridioides difficile infection where maximal medical therapy has been ineffective and surgery may carry an excessively high mortality risk.

Novel methodology to measure pre-procedure antimicrobial prophylaxis: integrating text searches with structured data from the Veterans Health Administration's electronic medical record.

BACKGROUND: Antimicrobial prophylaxis is an evidence-proven strategy for reducing procedure-related infections; however, measuring this key quality metric typically requires manual review, due to the way antimicrobial prophylaxis is documented in the electronic medical record (EMR). Our objective was to electronically measure compliance with antimicrobial prophylaxis using both structured and unstructured data from the Veterans Health Administration (VA) EMR. We developed this methodology for cardiac device implantation procedures. METHODS: With clinician input and review of clinical guidelines, we developed a list of antimicrobial names recommended for the prevention of cardiac device infection. We trained the algorithm using existing fiscal year (FY) 2008-15 data from the VA Clinical Assessment Reporting and Tracking-Electrophysiology (CART-EP), which contains manually determined information about antimicrobial prophylaxis. We merged CART-EP data with EMR data and programmed statistical software to flag an antimicrobial orders or drug fills from structured data fields in the EMR and hits on text string searches of antimicrobial names documented in clinician's notes. We iteratively tested combinations of these data elements to optimize an algorithm to accurately classify antimicrobial use. The final algorithm was validated in a national cohort of VA cardiac device procedures from FY2016-2017. Discordant cases underwent expert manual review to identify reasons for algorithm misclassification. RESULTS: The CART-EP dataset included 2102 procedures at 38 VA facilities with manually identified antimicrobial prophylaxis in 2056 cases (97.8%). The final algorithm combining structured EMR fields and text note search results correctly classified 2048 of the CART-EP cases (97.4%). In the validation sample, the algorithm measured compliance with antimicrobial prophylaxis in 16,606 of 18,903 cardiac device procedures (87.8%). Misclassification was due to EMR documentation issues, such as antimicrobial prophylaxis documented only in hand-written clinician notes in a format that cannot be electronically searched. CONCLUSIONS: We developed a methodology with high accuracy to measure guideline concordant use of antimicrobial prophylaxis before cardiac device procedures using data fields present in modern EMRs. This method can replace manual review in quality measurement in the VA and other healthcare systems with EMRs; further, this method could be adapted to measure compliance in other procedural areas where antimicrobial prophylaxis is recommended.