bluuebunny/crossref_metadata_2025_split huggingface dataset:
22. An Innovative Approach to Examining the Waning of Vaccine Effectiveness Using Automated Healthcare Data
Authors: Aukes Laurie , Bartlett Joan , Fireman Bruce , Hansen John , Lewis Ned , Marks Morgan , Saddier Patricia , Klein Nicola P 
Published: December 2021

Abstract

Background
We conducted a large real-world study of the long-term vaccine effectiveness (VE) of the live attenuated zoster vaccine (Zostavax; ZVL). Using an innovative approach with automated observational data we measured VE for incident herpes zoster (HZ) and severe HZ outcomes including post-herpetic neuralgia (PHN), herpes zoster ophthalmicus (HZO), and hospitalized HZ. This approach could be useful in long-term effectiveness studies of other vaccines.

Methods
We assessed VE against HZ, PHN, HZO and hospitalized HZ for up to 10+ years after vaccination at Kaiser Permanente Northern California. We identified incident cases using diagnoses, laboratory tests and prescriptions, and validated a sample by chart review. For each outcome, we used a Cox regression model with a calendar timeline to estimate VE in relation to year since vaccination. The model for HZ included 11 time-varying vaccination status indicators to denote -- at each timepoint during follow-up -- either the number of years since ZVL vaccination (30 days to &lt; 1 year, 1 to &lt; 2 years, . . ., and 10+ years) or that the individual is unvaccinated (reference group). Analyses were adjusted for demographics and time-varying measures of immune compromise status, healthcare use and comorbidities.

Results
From 2007-2018, 1.5 million people contributed to analyses; 507,000 (34%) were vaccinated. During 9 million person-years of follow-up, we observed 75,135 HZ cases, including 4,982 (7%) with PHN, 4,418 (6%) with HZO, and 555 (&lt; 1%) who were hospitalized. VE for HZ was 67% (95% Confidence Interval [CI]: 65-69%) in the first year after vaccination, waned to 50% (CI: 47-52%) in the second year after vaccination, and then waned more gradually to 15% (CI: 5-24%) by 10+ years after vaccination. Initial VE was higher against PHN (83%; CI: 78-87%) and hospitalized HZ (89%; CI: 67-97%) with less waning observed over time (42% by Year 8 for PHN and 53% in Years 5 to &lt; 8 for hospitalized HZ). VE against HZO was 71% in Year 1 and waned to 29% in Years 5 to &lt; 8.

Conclusion
Our large population, long follow-up and innovative methods let us estimate VE against HZ, PHN, HZO and hospitalized HZ for 10+ years after vaccination. Our approach could help assess waning and need for boosters for vaccines against other agents including COVID-19.

Disclosures
Morgan Marks, PhD, ScM, Merck & Co Inc. (Employee) Patricia Saddier, MD, PhD, Merck & Co Inc (Employee) Nicola P. Klein, MD, PhD, GlaxoSmithKline (Grant/Research Support)MedImmune (Grant/Research Support)Merck & Co Inc (Grant/Research Support)Pfizer (Grant/Research Support)Protein Sciences (now Sanofi Pasteur) (Grant/Research Support)Sanofi Pasteur (Grant/Research Support)
24. An analysis of the National Institutes of Health All of Us Research Database: Sociodemographic Disparities Among Patients Who Received Vaccinations
Authors: Ng Ding Quan , Jia Stanley , Cadiz Christine , Wisseh Cheryl , Nguyen Megan H , Lee Joyce , McBane Sarah , Nguyen Lee , Chan Alexandre , Hurley-Kim Keri 
Published: December 2021

Abstract

Background
The National Institutes of Health All of Us (AoU) research program is building a diversified database of 1 million+ adult subjects. With this database, we seek to describe the sociodemographic characteristics of those with documented vaccinations.

Methods
The AoU recruited subjects ≥ 18 years beginning in 2018. Eligible subjects were subsequently divided into five vaccine cohorts based on their vaccine history [influenza, hepatitis B (HepB), pneumococcal (Pneu) &lt; 65, Pneu ≥ 65, human papillomavirus (HPV)]. The vaccine cohorts were compared to the general AoU cohort. Subjects in the influenza cohort had documented influenza vaccinations from 09/2017-05/2018. Other vaccine cohorts comprised subjects with ≥ 1 lifetime record(s) of vaccination by 12/2018. The Pneu &lt; 65 and ≥ 65 cohorts comprised those who received pneumococcal vaccination before or after (inclusive) 65 years old, respectively. Descriptive statistics for all cohorts were generated using survey and electronic health record (EHR) data.

Results
We analyzed 315297 subjects in the AoU dataset R2020Q4R2. The cohort sizes were: influenza (n=15346), HepB (n=6323), HPV (n=2125), and Pneu (&lt; 65 n=15217; ≥65 n=15100). For all vaccine cohorts, comparing the 95% confidence intervals (CIs), the proportions of whites and non-Hispanics/Latinos were statistically higher than the general AoU cohort, the largest being from the Pneu ≥ 65 cohort (Table 1). For educational attainment, the Pneu &lt; 65 (36.5%) had the smallest proportion of college or advanced degree graduates while the largest was observed in the Pneu ≥ 65 cohort (59.0%). The proportions of subjects with &lt; &10k in annual household income (AHI) were largest among Pneu &lt; 65 (17.1%) and smallest among Pneu ≥ 65 (3.8%). In contrast, the largest proportion of subjects with ≥ &100k AHI was among Pneu ≥ 65 (25.3%) and the smallest among Pneu &lt; 65 (15.8%).
Table 1. Sociodemographic characteristics of subjects in the All of Us research program based on vaccine receipt

Conclusion
Racial and ethnic disparities in vaccinations were apparent. Pneumococcal vaccination at age 65 years and above was more prevalent among white, non-Hispanic/Latino subjects who were also more educated and affluent. Conversely, those receiving pneumococcal vaccination before age 65 years were less educated and had lower AHI.

Disclosures
All Authors: No reported disclosures
27. Immunologic Hyporesponsiveness with Subsequent Dosing of Meningococcal Vaccines: Re-Evaluating the Current Paradigm
Authors: Findlow Jamie , Balmer Paul 
Published: December 2021

Abstract

Background
Immunologic hyporesponsiveness (HyR) is considered as an inability to mount immune responses to vaccination of at least the same degree as earlier doses. For meningococcal vaccines, HyR has classically been associated with unconjugated but not conjugated polysaccharide (PS) vaccine dosing, but the clinical relevance is unclear.

Methods
To characterize meningococcal vaccine HyR, a PubMed search was conducted without date limits as follows: (hyporespons*) AND (meningococcal) AND (vaccine OR mechanism OR MOA OR causes). Papers from the authors’ files, including HyR insights with other vaccines, were included.

Results
Classic HyR with repeat unconjugated PS vaccine (MPV) dosing is thought to be associated with memory B-cell (BC) depletion, causing reduced responses on redosing with the same PS. This lack of immunologic memory and interference is seen years after MPV dosing across age groups. As data is added, other examples seem to fit the HyR definition but differ from the classical mechanism and its implications. First, passively transferred maternal antibodies (Abs) may interfere with neonatal adaptive immune response and ultimately those of childhood vaccination by binding to vaccine antigen (Ag) and inhibiting Ab production. Second, multiple dose schedules of meningococcal conjugate vaccines can show reduced responses to later doses in the series but memory is still established and amnestic booster response later achieved. Finally, carrier-induced epitopic suppression, occurring when PS Ag epitopes presented on a protein carrier are inhibited by prior/concurrent dosing with the same carrier, has also been reported. These 3 examples of alternative HyR mechanisms are not associated with memory BC depletion but are likely due to high circulatory Ab levels reducing responses, which is transient, reduces with Ab waning, immunologic memory remains intact, and is not clinically significant.

Conclusion
This literature review identified HyR mechanisms other than the classic mechanism associated with memory BC depletion that may account for decreased immune response to subsequent vaccination. Understanding the type of HyR observed with meningococcal vaccines is crucial, as these mechanisms vary in terms of potential clinical significance and the duration of their impact.

Disclosures
Jamie Findlow, PhD, Pfizer (Employee, Shareholder) Paul Balmer, PhD, Pfizer (Employee, Shareholder)
28. The Paradox of an Integrated MAT OPAT Program
Authors: Eckardt Paula , Reed Jessica , Vicencio Claudia P , Augsten Alberto 
Published: December 2021

Abstract

Background
Patients with substance use disorders (SUD), specifically opioid use disorder (OUD) and injection drug use (IDU) utilize healthcare resources for prolonged inpatient treatment of serious infections stemming from their addictions. For a variety of reasons, physicians treating these patients refuse to send these patients home to receive outpatient parenteral antimicrobial therapy (OPAT), and instead keep the patient in the hospital for several weeks or longer to complete treatment for the injection-related infections. Patients who do not have history of IDU are sent home with a PICC line to receive OPAT once they are no longer acutely ill and therefore no longer meet criteria to remain inpatient, which is the established standard of care. Patients with OUD and IDU are not allowed the same standard of care, and furthermore do not receive adequate, if any, therapy for their primary problem and reason for their serious infection – the addiction.
Flow chart of the MAT-OPAT process

Methods
Medication-assisted treatment (MAT) with buprenorphine-naloxone has been approved for treating adults with opioid use disorder as part of a comprehensive treatment program that also includes counseling and behavioral therapy. Until now in our healthcare system there has been no comprehensive and integrated program to safely discharge patients with OUD and IDU to receive OPAT via a PICC line, while simultaneously treating their addiction. We describe the implementation of a MAT-OPAT program. Please refer to the chart included.

Results
We present a successful case of a 36-year-old male with a history of endocarditis associated with IV drug use and the intervention of the Healthcare System to link the patient to appropriate Infectious disease, behavioral health and medication adherence treatment for opioid abuse. The patient completed the IV antibiotic therapy and remained enrolled in the behavioral health program with a successful outcome.

Conclusion
MAT-OPAT implementation in large healthcare system with continuous outpatient support that includes Infectious Disease services, behavioral health and drug abuse rehabilitation therapy can be a successful strategy to minimize readmisión, cost and complications in patients with history of IV drug use and infections that require prolonged intravenous antibiotic therapy.

Disclosures
All Authors: No reported disclosures
30. Implementation of the PEN-FAST Penicillin Allergy Screening Tool in the Emergency Department During Medication Reconciliation
Authors: Kaur Satwinder Sony , Adams David T , Parker Brittany 
Published: December 2021

Abstract

Background
The purpose of this study is to implement the PEN-FAST Penicillin Allergy Screening Tool in the emergency department to identify low risk patients with inappropriate penicillin-related allergies to transition them to a beta-lactam. Newly published, validated, penicillin allergy clinician decision tool (PEN-FAST) allows healthcare providers to identify low risk penicillin allergies with a negative predictive value of 96%. This quick, five question clinical decision tool allows healthcare providers and antimicrobial stewardship programs to identify patients who would also test negative if a formal penicillin allergy test was performed, making the process to confidently identify inappropriately labeled penicillin-related allergies more efficient.

Methods
During routine medication reconciliations, pharmacists will identify patients who have a documented penicillin-related allergy in the EMR and use the PEN-FAST screening tool. Patients meeting inclusion criteria will have their penicillin-related allergy updated in the EMR based upon their assessed risk of very low, low, moderate, or high. The primary outcomes for this study are the percentage of patients screened that were classified as “very low and low risk” and percentage penicillin-related allergies updated. The secondary outcomes are the percentage of patients that required antibiotic therapy (post-allergy update) that were transitioned to a beta-lactam, inpatient broad-spectrum antibiotic usage before and after allergy update, and time spent interviewing each patient.

Results
A total of 59 patients were interviewed using the PEN-FAST Tool. The results for the primary outcomes indicate 92% (n=54) of patient allergies updated in the EMR, 24% (n=13) of patients classified as “very low risk” and 34% (n=18) of patients classified as “low risk”. Results for the secondary outcome showed out of the 36 patients that were on non-beta lactams during allergy update, 72% (n=26) of those patients were transitioned to a beta-lactam. The average time to complete the PEN-FAST Tool was 4.2 minutes.

Conclusion
The results of this study support the use of the PEN-FAST Tool in efficiently updating patient’s allergies in the EMR and identifying low risk patients who may be eligible for beta-lactam therapy.

Disclosures
All Authors: No reported disclosures
34. Stemming the Rise in Antibiotic Prescription for Community Acquired Respiratory Infections (ARI) During COVID-19 Pandemic in Singapore General Hospital (SGH)
Authors: Lim Shena Yun Chun , Zhou Peijun Yvonne , Yii Daphne Yah Chieh , Hung Kai Chee , Lee Lai Wei , Liew Yi Xin , Lim Jia Le , Loo Li Wen , Koomanan Narendran , Chua Nathalie Grace Sy , Cherng Benjamin Pei Zhi , Thien Siew Yee , Lee Winnie , Kwa Lay Hoon Andrea , Chung Shimin Jasmine 
Published: December 2021

Abstract

Background
In early months of COVID-19 pandemic, SGH recorded a year-on-year increase in antibiotic (ABx) use for community acquired acute respiratory infection (CA ARI) from Feb-Apr 2019 (48.7 defined daily doses (DDD)/100 bed-days) to 2020 (50.8 DDD/100 bed-days). To address concerns of misuse, the antibiotic stewardship unit (ASU) expanded prospective audit feedback (PAF) to CA ARI patients admitted to ARI wards, with low procalcitonin (PCT). PAF was conducted on day 2-3 of ABx, on weekdays. Doctors received feedback to stop/modify when ABx was deemed inappropriate. Here, we describe the impact of ASU’s adaptive approach to curb rising ABx use in patients admitted for ARI during COVID-19 pandemic.

Methods
A Pre- & Post-intervention study was conducted. All patients started on ABx (ceftriaxone/co-amoxiclav/piptazo/carbapenems/levofloxacin) for CA ARI & PCT &lt; 0.5µg/L were analysed. Those who died ≤48h of admission; admitted to intensive care; required ABx escalation; &gt;1 infective sites; complex lung infection were excluded. Primary objective was to compare the proportion of ABx stopped ≤4 days (time to final infection diagnosis) Pre (22/3-18/4/20) & Post (21/4-13/7/20).

Results
184 (Pre) & 528 (Post) ABx courses were analysed. ASU audited 51 (Pre) & 380 (Post) courses with the rest discontinued/discharged before review. Patients were largely similar in both periods; a third had low likelihood of bacterial infection (C reactive protein &lt; 30mg/L). In Post, 73 feedback was given to stop ABx (often because symptoms suggested viral/fluid overload) & 18 to switch to oral ABx. 82 (90%) feedback was accepted. No ABx was restarted ≤48h or deaths ≤30 days due to ARI. 1 patient had C. difficile diarrhoea a day after ABx cessation as per ASU feedback.
Proportion of all ABx stopped ≤4 days was higher in Post than Pre [27/184 (15%) vs 152/528 (29%), p&lt; 0.01]. Median duration of therapy of IV ABx was reduced (6.5 vs 3 days, p&lt; 0.01), with corresponding shorter median length of stay (10.5 vs 6 days, p&lt; 0.01).

Conclusion
PAF directly and indirectly reduced ABx duration in patients treated for CA ARI as prescribers become more conscious about stopping ABx when investigations show low likelihood of bacterial infection. ASU must remain agile during pandemics to detect emerging problems and adapt processes to counter early.

Disclosures
All Authors: No reported disclosures
36. Evaluation of a Best Practice Alert (BPA) to Improve Pneumocystis jirovecii Prophylaxis Prescribing in Cancer Patients Receiving High-dose Corticosteroids in an Outpatient Setting
Authors: Ross Justine Abella , Tegtmeier Bernard , Johnson Deron , Nanayakkara Deepa , Puing Alfredo , Ho Stephanie , Taplitz Randy , Dadwal Sanjeet , Dickter Jana 
Published: December 2021

Abstract

Background
In patients (pts) with cancer, the risk of Pneumocystis jirovecii pneumonia (PJP) is a function of dose and duration of corticosteroids (CS), underlying immunodeficiency, and immunosuppressive drugs. Trimethoprim/sulfamethoxazole (TMP/SMX) and atovaquone (ATO) are effective prophylaxis (ppx) agents against PJP. Guidelines recommend PJP ppx for pts on &gt; 20 mg /day of prednisone or its equivalent for ≥ 1 month. A best practice alert (BPA) to identify pts receiving CS may assist with improving PJP ppx prescribing in cancer pts.

Methods
PJP BPA was created to identify pts on CS (excluding hydrocortisone) with no active prescription for TMP/SMX or ATO ppx in EMR. Dapsone and pentamidine excluded since not preferred agents at our institution. PJP case: positive PJP polymerase chain reaction (PCR) from bronchoalveolar lavage (BAL) &gt; 84 copies or positive PJP direct fluorescent antibody (DFA) or cytology with clinical and radiographic suspicion. PJP PCR from BAL &lt; 84 copies/ml with negative DFA and cytology excluded. Preventable PJP (P-PJP): pts after CS &gt; = 30 days without PJP ppx. Non-preventable PJP (NP-PJP) : pts after CS &lt; 30 consecutive days, or on PJP ppx (non-compliance, failure), or day +1 to +30 post hematopoietic cell transplant (HCT). Pre-intervention (pre-i) PJP pts 3/1/2018 to 7/31/19 (17 months), post-intervention (post-i) PJP pts 8/1/19 to 2/1/20 (18 months) evaluated to assess BPA impact on PJP inpatient (inpt) admissions.

Results
In the post-i, the BPA fired 3,588 times in 1,302 pts. Pre-i: 20 P-PJP, 13 NP-PJP out of 33 pts. Post-i: 6 P-PJP, 25 NP-PJP out of 31 pts. The BPA fired in 4/31 PJP pts in the post-i period: 2/6 of P-PJP, 2/25 NP-PJP. The number of P-PJP decreased from 20 to 6 in the post-i period (p=0.0097).

Conclusion
Implementation of a decision support tool significantly decreased the number of P-PJP. The BPA was limited by identifying pts after CS were prescribed after the initial visit leading to periods of CS use without ppx and inability to calculate CS dosing and length of prescription. BPA provided passive education in the outpatient setting and future opportunities include refining the EMR to better identify pts at risk for developing PJP.

Disclosures
All Authors: No reported disclosures
37. Impact of a Vancomycin/Piperacillin-tazobactam Audit and Feedback Program
Authors: Atluri Vidya , Tverdek Frank , Elsayed Sarah , Chan Beverly , Liu Catherine , Pottinger Paul , Jain Rupali 
Published: December 2021

Abstract

Background
Vancomycin and piperacillin-tazobactam (VPT) combination therapy is associated with nephrotoxicity and provides broad-spectrum coverage that may be unnecessary. We conducted a pre-post implementation study to assess the impact of an audit and feedback program for VPT at our academic medical center.

Methods
Automated alerts were used to identify patients on VPT at the University of Washington Medical Center (UWMC)-Montlake (ML) and UWMC-Seattle Cancer Care Alliance (SCCA) hospitals. Baseline data was collected on patients from 1/20/20-6/2/20: electronic medical records were reviewed for antibiotic indication, duration, renal function, and presence of Infectious Disease (ID) consult. From 6/25/20-10/31/20, all patients on combination therapy without an ID consult were reviewed by the antimicrobial stewardship programs at ML and SCCA, respectively. If intervention was warranted, the ML steward discussed the case with the provider then documented the conversation. The SCCA steward, instead, discussed the case with the team pharmacist. The primary outcome was change in VPT duration post intervention. Secondary outcomes included nephrotoxicity rates and carbapenem escalation.

Results
Prior to the intervention, 66 ML and 33 SCCA patients were started on the combination compared to 110 ML and 50 SCCA patients post-intervention. Overall, 50% of ML and 14% of SCCA patients were on surgical primary services. Amongst ML patients, there was a decrease in patients on VPT for &gt; 4 days (22 % to 8%), incidence of renal injury (30.3% to 10%), and percentage of ID consults (53.0% to 43.6%). Escalation to a carbapenem was stable (4.5% to 4.5%). In SCCA patients the percentage of patients on VPT for &gt; 4 days decreased slightly (18.2% to 15.2%), incidence of renal injury was stable (18.2% to 18%), percentage of ID consults increased (45.5% to 50.0%), and escalation to a carbapenem was stable (12.1% vs 13.5%).

Conclusion
Prospective audit and feedback of VPT was associated with a decrease in duration and nephrotoxicity in ML but not SCCA patients. The difference in outcomes could be due to the patient populations, primary services, or intervention process. This study highlights the importance of tailoring interventions even within the same medical system.

Disclosures
All Authors: No reported disclosures
38. Impact of Antimicrobial Stewardship Interventions on Adherence to Clostridioides difficile Treatment Guidelines
Authors: Neuner Elizabeth , Krekel Tamara , Durkin Michael , Dubberke Erik R , Hseuh Kevin 
Published: December 2021

Abstract

Background
Facility-specific treatment guidelines are a priority intervention recommended in the CDC Core Elements of Hospital Antimicrobial Stewardship Programs (ASPs). Our ASP sought to improve adherence to the facility C. difficile infection (CDI) treatment guideline by implementing prospective audit and feedback of CDI cases, changing fidaxomicin from being restricted to Infectious Diseases consult use, to only requiring prospective audit and feedback, and allowing fidaxomicin and oral vancomycin orders only through the order set. This study reviews the impact of these interventions.

Methods
This single-center retrospective quasi-experimental study evaluated inpatient CDI lab events 3 months pre-intervention (10/1/2019-12/31/2019) and post-intervention (10/14/2020-1/14/2021). Patient and treatment data was evaluated via chart review. The primary outcome was adherence to CDI treatment guideline. ASP intervention types were categorized. Statistical analyses were performed using Chi-squared or Fischer’s exact, where appropriate.

Results
Baseline characteristics were well matched between the 58 and 70 patients pre and post intervention respectively (Table 1). ASP interventions resulting from the prospective audit and feedback are described in Table 2 and overall acceptance rates were high (88%). Guideline adherence improved significantly from 71% pre to 90% post-intervention (p=0.005). Reasons for non-adherence included vancomycin dose incorrect for the severity of illness (9 pre vs 2 post), inappropriate duration (4 pre vs 0 post), use of combination therapy in non-fulminant disease (5 pre vs 3 post), and not using fidaxomicin for recurrent disease (3 pre vs 2 post). Clinical outcomes pre and post intervention were not different in this small sample size: colectomy 1 (2%) vs 1 (1%) p=1, 60 day all- cause mortality 15 (26%) vs 14 (20%) p=0.43, and CDI recurrence at day 60 9/43 (21%) vs 5/56 (9%) p=0.131.

Conclusion
A bundle of ASP interventions including prospective audit and feedback of CDI cases improved adherence to facility-specific CDI treatment guidelines.

Disclosures
Tamara Krekel, PharmD, BCPS, BCIDP, Merck (Speaker’s Bureau) Erik R. Dubberke, MD, MSPH, Ferring (Grant/Research Support)Merck (Consultant)Pfizer (Consultant, Grant/Research Support)Seres (Consultant)Summit (Consultant)