bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of Bupropion and Varenicline for Smokers With Baseline Depressive Symptoms
Authors: Zhang Helena , Gilbert Emily , Hussain Sarwar , Veldhuizen Scott , Le Foll Bernard , Selby Peter , Zawertailo Laurie 
Published: December 2022

AbstractIntroductionSmokers with concurrent depression are less likely to achieve abstinence, even with pharmacotherapy. The purpose of this secondary data analysis was to evaluate if the presence of any depressive symptoms at baseline alters the effectiveness of bupropion and varenicline for smoking cessation.Aims and MethodsEligible participants were enrolled via the internet and randomized 1:1 to receive a 12-week supply of either bupropion (n = 465) or varenicline (n = 499). Depressive symptoms were assessed using the Patient Health Questionnaire (PHQ-2). Follow-up surveys were conducted at weeks 4, 8, 12, 26, and 52 to assess self-reported quit. The primary outcome was 7-day point prevalence abstinence at 12 weeks follow-up (end-of-treatment).ResultsParticipants who endorsed any depressive symptoms (PHQ-2 &gt; 0; n = 280) were less likely to be quit at end-of-treatment compared to participants who did not endorse any symptoms (PHQ-2 = 0; n = 684) (OR = 0.56, 95% CI: 0.38 to 0.8, p = .003). Within the varenicline group, quit outcomes did not differ between those with and without depressive symptoms (21.3% vs. 26.9%, respectively). Within the bupropion group, however, those with symptoms had a significantly reduced quit rate compared to those without symptoms (7.0% vs. 17.3%, respectively).ConclusionsThe presence of even one symptom of depression at the start of a quit attempt may adversely affect quit outcomes. Patients should be assessed for depressive symptoms when planning to quit smoking as it may inform the approach to treatment. However, future studies are needed to confirm these findings.ImplicationsFindings from the current study illustrate the importance of evaluating baseline sub-clinical depressive symptoms before a quit attempt using first-line pharmacotherapies. This secondary analysis of a large-scale randomized trial suggests that bupropion may be less effective for those with baseline depressive symptoms while varenicline may be equally effective for those with and without depressive symptoms
Umbrella review of time-restricted eating on weight loss, fasting blood glucose, and lipid profile
Authors: Chew Han Shi Jocelyn , Ang Wei How Darryl , Tan Zhen Yang Abel , Ang Wen Wei , Chan Kin Sun , Lau Ying 
Published: December 2022

AbstractContextA growing number of systematic reviews with meta-analyses have examined the effectiveness of time-restricted eating (TRE) in reducing weight and improving fasting blood glucose and lipid profiles. However, mixed results have been found, and its effectiveness remains uncertain.ObjectiveThis umbrella review aimed to summarize systematic reviews that (1) examine the effects of TRE on weight loss, fasting blood glucose, total cholesterol, triglycerides, high-density-lipoprotein cholesterol (HDL-C) and low-density-lipoprotein cholesterol (LDL-C) in individuals with overweight and obesity; and (2) compare the effect sizes on these outcomes between conventional TRE and Ramadan fasting.Data SourcesA total of 11 databases were searched from inception until March 11, 2022.Data ExtractionTwo independent reviewers performed article selection, data extraction, and quality assessment.Data AnalysisSeven systematic reviews with 30 unique meta-analyses involving 7231 participants from 184 primary studies were included. The quality of each review was evaluated as moderate (14.3%) or critically low (85.7%) according to the Assessment of Multiple Systematic Reviews 2. The degree of overlap was rated as slight for all outcomes (corrected cover area = 1.04%–4.27%). Meta-analyses at the meta-data level suggest that TRE is beneficial for reducing weight (P = .006) and fasting blood glucose (P &lt; .01). Meta-analyses at the primary study level suggest that the effect on LGL-C was significant (P = .03). Subgroup analyses revealed greater effects in lowering fasting blood glucose, total cholesterol, and LDL-C from Ramadan fasting than from conventional TRE. The credibility of evidence was rated as suggestive (3.3%), weak (36.7%) or nonsignificant (60%) using a classification method.ConclusionTRE may complement usual care and reduce body weight and fasting blood glucose. Rigorous randomized controlled trials with long-term assessments in a wide range of populations are warranted.Systematic Review RegistrationPROSPERO registration no. CRD42022325657.
79. Long-term Health Outcomes of Individuals who are Infected with SARS-CoV-2 and Develop COVID-19
Authors: Tene Lilac , Bergroth Tobias , Eisenberg Anna , Chodick Gabriel 
Published: December 2022

Abstract

Background
Persistence of symptoms after the acute phase of COVID-19, often referred to as long COVID, is common and debilitating. Data on the burden and direct medical costs of long COVID is still limited.

Methods
A retrospective cohort study using data from a 2.6-million-member state-mandated health provider in Israel.
All adult patients with a positive SARS-CoV-2 RT-PCR test between March 2020 and March 2021 were included. Among them, patients with long COVID diagnoses or post-COVID symptoms persisting or newly diagnosed more than 4 weeks from the first positive RT-PCR test were defined as long COVID patients. Study endpoints included all COVID-related visits, hospitalizations, therapies, imaging, and lab tests. Costs of utilized healthcare service were evaluated for pre-infection, acute phase, and long COVID period.

Results
Included in the study were 180,759 incident COVID-19 patients (32.9±19.0 years; 89,665 [49.6%] females). 14,088 (7.8%) individuals developed long COVID (40.0±19.0 years; 52.4% females). In addition to older age (adjusted odds ratio (AOR)=1.06, 95% CI 1.05–1.06), long COVID was associated with female sex (AOR=1.14, 95% CI 1.10–1.18), ever smoking (AOR=1.53, 95% CI 1.36–1.73), symptomatic acute phase (AOR=1.17; 95% CI 1.13–1.22); and hypertension (AOR=8.21, 95% CI 6.80–9.90), particularly among younger adults. Hospitalization in Long COVID patients was associated with respiratory/ear-nose-throat (adjusted hazard ratio (AHR)=2.55; 95% CI 2.27–2.86), neurological (AHR=2.88; 95% CI 2.33–3.56), psychiatric (AHR=2.32; 95% CI 1.93–2.79), and cardio-metabolic long-term complications (AHR=1.61; 95% CI 1.41–1. 83). While long COVID patients had a lower use of services compared to non-long COVID patients during the acute phase (AOR=0.87; 95% CI 0.83–0.90), their mean cost per user was 52% higher. Direct medical costs of long COVID patients were substantially greater than non-long COVID patients post vs. pre infection (AOR=1.74; 95% CI 1.56–1.93).

Conclusion
This study demonstrated the association of long COVID with many complications requiring extended medical care and higher healthcare costs. These factors should be considered in priority setting around COVID-19 prevention and management.

Disclosures
Tobias Bergroth, PhD, Gilead Sciences: Stocks/Bonds|MSD, Sweden: Employee|MSD, Sweden: Stocks/Bonds Anna Eisenberg, PhD, MSD, Israel: Employee|MSD, Israel: Stocks/Bonds.
739. The High Burden of Bloodstream Infection in Adults: A Nation-Wide Population- Based Study
Authors: Schechner Vered , Wullfhart Liat , Temkin Elizabeth , Feldman Sarah F , Nutman Amir , Shitrit Pnina , Schwaber Mitchell J , Carmeli Yehuda 
Published: December 2022

Abstract

Background
Limited data exist on the long-term consequences of bloodstream infections (BSI). We examined incidence, 1-year mortality, and years of potential life lost (YPLL) following BSI by eight sentinel bacteria in adults. We also estimated the relative contribution of hospital-onset BSI (HO-BSI) and of antibiotic-resistant BSI to the burden of BSI.

Methods
We used data from Israel's national BSI surveillance system (covering E. coli, K. pneumoniae, P. aeruginosa, A. baumannii, S. pneumoniae, S. aureus, E. faecalis and E. faecium, comprising 70% of all BSI) and the national death registry. Adults with BSI between 1/1/2018 and 31/12/2019 were included. The outcomes were all-cause 30-day and 1-year mortality. We constructed Kaplan-Meier curves and used the log-rank test to compare survival between age groups. We calculated the age-standardized mortality rate and YPLL using the Global Burden of Disease reference population and life expectancy tables.

Results
A total of 25,376 BSI occurred over 2 years in the adult Israeli population (mean adult population: 6,068,580). Drug-resistant BSI comprised 32% of all events (41.1% of HO-BSI). The annual BSI incidence was 209 per 100,000 population. The case fatality rate (CFR) was 25.6% at 30 days and 46.4% at 1 year. The 1-year CFR was higher among males than females (RR=1.17, 95% CI 1.14–1.20) and it increased with age (OR=1.37 per decade, 95% CI 1.36–1.39). In all age groups survival continued to decline up to 1 year (Figure). For the outcome of 1-year mortality, the annual age-standardized mortality rate and YPLL per 100,000 population following BSI were 48.6 and 1002.2, respectively. For comparison, the global mortality rate and YPLL from ischemic stroke are 36.6 and 521.8 per 100,000, respectively. HO-BSI represented 27.4% of BSI but contributed to 33.9% of deaths and 39.9% of YPLL. HO-BSI by drug-resistant bacteria represented 11.3% of BSI, 14.8% of deaths, and 17.4% of YPLL.

Conclusion
BSI have grave long-term consequences: nearly 50% of affected adult patients died within 1 year. The burden of BSI is higher than that of ischemic stroke. HO-BSI and drug-resistant BSI contribute disproportionately to BSI mortality and YPLL. Attention and resources should be directed to prevention of BSI, as well as to advances in early diagnosis and better treatment.

Disclosures
Yehuda Carmeli, MD, Allecra Therapeutics: Advisor/Consultant|MSD: Advisor/Consultant|Nabriva: Advisor/Consultant|Pfizer: Advisor/Consultant|Qpex Pharmaceuticals: Advisor/Consultant|Roche: Advisor/Consultant|Shinogi: Advisor/Consultant|Spero Therapeutics: Advisor/Consultant.
744. Infectious Diseases Providers Perspectives Around the Use of Outpatient Parenteral Antibiotic Therapy (OPAT) for Persons Who Inject Drugs (PWID), US, 2022
Authors: Solomon Daniel A , Beieler Alison M , Levy Sera , Eaton Ellen , Sikka Monica K , Thornton Alice C , Dhanireddy Shireesha 
Published: December 2022

Abstract

Background
Injection drug use-related infections are life threatening and may require prolonged courses of antibiotic therapy. There is no consensus on best practices for serious infections when patients are stable for discharge. Outpatient parenteral antimicrobial therapy (OPAT) has been shown to be feasible for people who inject drugs (PWID) especially when paired with medication for opioid use disorder. We set out to determine the current practice patterns and attitudes of infectious diseases (ID) clinicians in the United States regarding the use of OPAT for PWID.

Methods
We surveyed ID clinicians between January 2022 and March 2022. Topics focused on PWID including OPAT access, barriers to inclusion in OPAT, and factors clinicians considered for OPAT success. Responses from those who perceived PWID were eligible for OPAT (PWID-E) were compared to those who believed PWID were ineligible (PWID-I) using the Pearson chi-squared test.

Results
Of 239 clinician respondents, 80% were MD, 6% DO, 5% NP, 2% PA, and 7% Pharmacists. 187 (78.2%) work at an academic practice and 179 (75%) work in an urban setting. 182 (76%) respondents have access to inpatient addiction medicine services and 206 (86%) reported availability of outpatient addiction treatment, but only 86 (36%) described patient access to outpatient services as “good” or “excellent.”
Respondents were categorized as PWID-E (n=171, 72%) and PWID-I (n=68, 28%). Of the PWID-E group, only 48 (28%) have an institutional policy for determining eligibility. There was no significant difference in practice setting or access to addiction services between PWID-E and PWID-I. Access to inpatient and outpatient social work/case management was significantly higher for PWID-E. (Table 1).
Clinicians reporting PWID-I were more likely to cite risk of tampering with PICC (76.5% vs 62.6%, p = 0.04) and medical-legal risk (47.1% vs 19.3%, p &lt; 0.001) as barriers to OPAT. (Table 2).

Conclusion
A high proportion of respondents to this national survey offer OPAT for PWID, but only a minority have an institutional policy for eligibility. Guidelines that outline a framework for discharge decision making, education regarding medical and legal risk, and development of best practices may help to standardize care across settings.

Disclosures
Ellen Eaton, MD, MPH, Gilead HIV Research Scholar: Grant/Research Support|Gilead HIV research scholar: Grant/Research Support Monica K. Sikka, MD, F2G: Site research investigator.
781. COVID-19 Outcomes in the Immunocompromised Population of the COVID-19 Community Research Partnership
Authors: Williamson John C , Strylewicz Gregory B , DeWitt Michael E , Uschner Diane , Soni Ashvi , Mongraw-Chaffin Morgana , Dantuluri Keerti L , Hinkelman Amy , Gibbs Michael A , Lagarde William H , Weintraub William , Bott Matthew , Ostasiewski Brian , Miller Kristen , McCurdy Lewis , Sanders John W , Herrington David M 
Published: December 2022

Abstract

Background
The COVID-19 Community Research Partnership (CCRP) is a large multicenter healthcare system-based study of the COVID-19 pandemic, including factors impacting risk of infection and hospitalization. The CCRP includes a subset of immunocompromised (IC) participants with varying vaccination status over time.

Methods
We conducted an observational cohort study of 2,515 IC and 41,941 non-IC CCRP participants who contributed electronic health record data and daily electronic surveys to self-report COVID-19 symptoms, test results, and vaccinations from April 2020 to March 2022. The IC population included those with stem cell transplant, HIV, cancer, autoimmune disease, or solid organ transplant. The latter 3 must have also had an active systemic therapy to meet the IC condition (e.g. chemotherapy, immune modulator, steroid). Logistic regression was used to investigate risk of COVID-19 and hospitalization among IC participants and according to vaccine status within viral variant time periods (pre-delta, delta, omicron).

Results
IC conditions included cancer (51%), autoimmune (41%), solid organ/stem cell transplant (9%), and HIV (7%). The IC group was older and had more comorbidities. 95% of vaccine recipients received an mRNA vaccine. More vaccine breakthrough infections occurred in the IC group than non-IC group (36.1% vs 29.5%, p&lt; 0.001). IC participants were less likely to remain COVID-19 free over time if vaccinated but not boosted (Fig 1A). However, after receiving a booster there was no difference in COVID-19 cases between the groups (Fig 1B). IC participants were more likely to be hospitalized with COVID-19 (OR 2.85; 95% CI 1.69–4.76), but vaccination reduced risk for hospitalization (OR 0.26; 95% CI 0.08–0.8). Receipt of a booster dose reduced risk of COVID-19 among IC participants during the delta wave (IRR 0.52; 95% CI 0.28–0.94) but not during omicron. However, during omicron risk of hospitalization in the IC group was reduced by a booster dose (OR 0.13; 95% CI 0.02–0.72).

Conclusion
IC individuals were at increased risk for COVID-19 hospitalizations and breakthrough infections. After receiving a booster, IC participants were conferred the same level of protection from infection as their non-IC counterparts, highlighting the importance of boosters for these individuals.

Disclosures
All Authors: No reported disclosures.
785. Bacterial Co-infection and Empirical Antibiotic Therapy in Patients with COVID-19
Authors: Lee Jiyoung , Jung Jiwon , Kim Min Jae , Chong Yong Pil , Kim Sung-Han , Lee Sang-Oh , Choi Sang-Ho , Kim Yang Soo , Bae SeongMan 
Published: December 2022

Abstract

Background
Understanding the rate and composition of bacterial co-infection is important to determine antibiotic therapy in SARS-CoV-2 infection, but those vary according to healthcare settings and regional differences. We evaluated the rate of bacterial co-infection in hospitalized patients with COVID-19 in a single tertiary hospital in South Korea.

Methods
In this retrospective study, all the adult patients with COVID-19 hospitalized between Feb 2020 and Dec 2021 were included. Bacterial co-infection rate was assessed by results of sputum cultures, blood cultures, pneumococcal urinary antigen, Legionella urinary antigen, sputum Legionella pneumophilia PCR, and sputum multiplex PCR for Mycoplasma pneumoniae and Chlamydia pneumoniae. Characteristics and outcomes of patients were evaluated according to antibiotics exposure prior to hospitalization.

Results
Of 367 adult patients, 300 (81.7%) patients having sputum culture results were included in the analysis. Of these, 127 (42.3%) had a history of antibiotic exposure within 1 month before hospitalization. The coinfection rate within 48 hours of hospitalization was confirmed in 8.3% (25/300): 6.4% (11/163) of patients without prior antibiotic exposure and 11% (14/127) of patients with prior antibiotic exposure. In the group without prior antibiotic exposure, pathogens responsible for community-onset infections were isolated, whereas nosocomial pathogens were predominantly isolated in the antibiotic-exposed group. Empirical antibiotics were used in 144 (66%) of 275 patients without positive results for microbiological tests. Empirical antibiotic use in patients without positive results for microbiological tests was not significantly associated with 30-day mortality or in-hospital mortality after adjusting covariates including age, sex, comorbidity, anti-inflammatory treatment, and COVID-19 severity.

Conclusion
In this study with a high rate of microbiological testing, bacterial co-infection was not frequent, and the results varied depended on previous exposure to antibiotics. Given the rarity of bacterial co-infection and the lack of potential benefits of empirical antibiotic therapy, the antibiotic use in patients with COVID-19 should be restricted as an important target of antibiotic stewardship.

Disclosures
All Authors: No reported disclosures.
791. ICU Provider Overestimation of Ventilator-Associated Pneumonia Diagnostic Probability: An Opportunity for Diagnostic Stewardship
Authors: Soper Nathaniel , Albin Owen 
Published: December 2022

Abstract

Background
Overdiagnosis of ventilator-associated pneumonia (VAP) is common in intensive care units (ICUs). Because VAP is a clinical diagnosis without an easily accessible confirmatory diagnostic test, understanding how ICU physicians practice diagnostic reasoning in suspected VAP is vital to informing diagnostic stewardship efforts. We aimed to assess the accuracy of ICU practitioner estimates of VAP diagnostic probability.

Methods
We conducted a survey of physicians at Michigan Medicine ICUs. Providers were presented with clinical vignettes (Figure 1) in which mechanically ventilated patients developed clinical signs suggestive of VAP and then had radiographic/microbiologic tests performed. Providers were asked to estimate the probability of VAP before and after each presented clinical sign or test result, which were then used to impute provider-estimated likelihood ratios (pLRs) for each clinical sign and diagnostic test. Provider-estimated probabilities and LRs were compared to evidence-based VAP probabilities and LRs (eLRs) derived from systematic reviews and meta-analyses.
Survey Case Example.

Results
Of 102 survey respondents, 54% felt moderately to extremely confident in their ability to accurately diagnose VAP. Providers significantly overestimated the pre and post-test probability of VAP in all clinical scenarios (provider-estimated VAP diagnostic probabilities are visualized using density plots relative to evidence-based diagnostic probability in Figure 2). Median pLRs for nearly all VAP clinical signs and diagnostic tests were also significantly higher than eLRs (Figure 3), most notably for isolated purulent endotracheal secretions (pLR 1.54 vs eLR 0.76, p&lt; 0.01), positive chest radiograph (pLR 6.0 vs eLR 3.55, p&lt; 0.01), and positive bronchoalveolar lavage culture (pLR 5.7 vs eLR 1.37, p&lt; 0.01).
Density Plots of Provider-Estimated vs Evidence-Based Diagnostic Probability of Ventilator-Associated Pneumonia.
Provider-Estimated vs Evidence-Based Diagnostic Likelihood Ratios for Clinical Signs and Test Results Related to Ventilator-Associated Pneumonia.

Conclusion
Physicians routinely overestimated the diagnostic probability of VAP and the positive LRs of possible VAP clinical signs, as well as VAP diagnostic radiographic and microbiologic tests. Educational initiatives addressing and calibrating ICU providers’ perceptions of VAP diagnostic probability warrant investigation as an antimicrobial stewardship tool.

Disclosures
Owen Albin, MD, Charles River Laboratory: Advisor/Consultant|Cipla Pharmaceuticals: Advisor/Consultant|Shionogi Inc: Advisor/Consultant.
872. Voriconazole Therapeutic Drug Monitoring (TDM): How Common is Autoinduction?
Authors: Tyagi Varalika , Lau Cecilia , Doucette Karen , Cervera Carlos , Professor Associate , Kabbani Dima 
Published: December 2022

Abstract

Background
Therapeutic drug monitor (TDM) guided optimized dosing of Voriconazole allows optimal drug exposure in the management of mold infection (MI). In addition to already known nuances in pharmacokinetics such as CYP2C19 genetic polymorphism and the role of drug interactions both necessitating TDM, case reports have suggested that auto-induction may occur after initially achieving a therapeutic level. We assessed whether the levels of Voriconazole can change over time and become subtherapeutic due to auto-induction.

Methods
We prospectively enrolled, adults ≥ 18 y.o of age, on Voriconazole for the treatment of MI at the University Of Alberta Hospital. After achieving an initial therapeutic margin, (1–5.5mg/l), we monitored Voriconazole levels twice a month, using high-performance liquid chromatography, until discontinuation or at 12 weeks of therapy. We calculated the incidence of Voriconazole sub-therapeutic concentrations (auto-induction) defined as drop of Voriconazole level below one, with previous concentrations between the therapeutic margins of 1–5.5 mg/L. Adjustment of Voriconazole dosing in case of auto-induction was at the discretion of the treating physician. The excess Voriconazole dose adjustment was calculated in patients where dosing was increased.

Results
Between January 2021 and April 2022, we enrolled 12 patients. Median age (IQR) was 62 (52–73), and 25 % were female. Patient characteristics are in table 1. Auto-induction was observed in 6/10 (60%) who completed 12 weeks follow up blood work. Median time to auto-induction was of 46 days (39–55). Voriconazole dosing was increased in 4/6 patients with auto-induction. Of the four patients with dose adjustment, the cumulative Voriconazole dose was 13% higher than expected, which correspond to 5,300 mg excess Voriconazole per patient to maintain therapeutic levels.

Conclusion
Auto-induction is common in patients treated with Voriconazole. Future studies are needed to assess if undetected auto-induction affects outcomes.
Funding: AVIR Pharma.

Disclosures
Carlos Cervera, Associate Professor, Astra-Zeneca: Advisor/Consultant|AVIR Pharma: Grant/Research Support|AVIR Pharma: Honoraria|Lilly: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Sunovion: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Honoraria|VerityPharma: Advisor/Consultant Dima Kabbani, MD, MSc, AVIR Pharma: Grant/Research Support|AVIR Pharma: Honoraria|GSK: Honoraria|Merck: Grant/Research Support.