Search

OBJECTIVE Chronic subdural hematomas (cSDHs) are particularly common in older adults who have increased risk of falls and the conditions that require anticoagulants (ACs). In such cases, clinicians are often left with the dilemma of co-managing the cSDH and the ongoing need for ACs. METHODS Patients who underwent surgical management for cSDH at the authors’ institution between January 2006 and June 2022 were identified. Propensity score–matched analysis was used to obtain a balance in patients who were on ACs before the procedure versus those who were not, and in patients who were on ACs postprocedure versus those who were not. Length of hospitalization, periprocedural complications, reintervention rate during the same admission, rebleeding risk, and reintervention rates after discharge were compared. RESULTS In total, 104 patients were on long-term ACs before the procedure, whereas 372 were not. After matching, 55 pairs were included in the analysis. Postprocedure, 74 patients were started on long-term ACs; the rest were not. A total of 49 patients in each group were then included in the analysis after matching. Comparing the preprocedure AC group with the non-AC group, no significant differences were found in length of hospitalization (8.5 ± 6.7 days vs 8.1 ± 7.7 days, p = 0.75), periprocedural complications (7.3% vs 7.3%, p > 0.99), or reintervention during the same admission (1.8% vs 5.5%, p = 0.31). In the comparison of postprocedure AC and non-AC groups, no significant differences were seen in recurrence rate (8.2% vs 14.3%, p = 0.52), reintervention rate after discharge (4.1% vs 14.3%, p = 0.16), or disability (i.e., mRS ≤ 2; 83.7% vs 89.8%, p = 0.55). CONCLUSIONS Being treated with long-term ACs before cSDH procedures does not affect length of hospitalization, periprocedural complications, or reintervention during the same admission. Similarly, administration of long-term ACs after a procedure for cSDH does not increase rebleeding risk or reintervention rate. Patients who are on long-term ACs can have similar interventions to those who are not on ACs. In addition, it is safe to restart patients on AC agents in a 7- to 14-day window after admission for cSDH with or without acute/subacute components.

OBJECTIVE Middle meningeal artery embolization (MMAE) is an emerging endovascular treatment technique with proven promising results for chronic subdural hematomas (cSDHs). MMAE as an adjunct to open surgery is being utilized with the goal of preventing the recurrence of cSDH. However, the efficacy of MMAE following surgical evacuation of cSDH has not been clearly demonstrated. The authors sought to compare the outcomes of open surgery followed by MMAE versus open surgery alone. METHODS Patients who underwent surgical evacuation alone (open surgery–alone group) or MMAE along with open surgery for cSDH (adjunctive MMAE group) were identified at the authors’ institution. Two balanced groups were obtained through propensity score matching. Primary outcomes included recurrence risk and reintervention rate. Secondary outcomes included decrease in hematoma size and modified Rankin Scale (mRS) score at last follow-up. Variables in the two groups were compared by use of the Mann-Whitney U-test, paired-sample t-test, and Fisher’s exact test. RESULTS A total of 345 cases of open surgery alone and 52 cases of open surgery with adjunctive MMAE were identified. After control for subjective confounders, 146 patients treated with open surgery alone and 41 with adjunctive MMAE following open surgery with drain placement were included in the analysis. Before matching, the rebleeding risk and reintervention rate for open surgery trended higher in the open surgery alone than the open surgery plus MMAE group (14.4% vs 7.3%, p = 0.18; and 11.6% vs 4.9%, p = 0.17, respectively). No significant differences were seen in duration of radiographic or clinical follow-ups or decreases in hematoma size and mRS score at last follow-up. After one-to-one nearest neighbor propensity score matching, 26 pairs of cases were compared for outcomes. Rates of recurrence (7.7% vs 30.8%, p = 0.038) and overall reintervention (3.8% vs 23.1%, p = 0.049) after open surgery were found to be significantly lower in the adjunctive MMAE group than the open surgery–alone group. With one-to-many propensity score matching, 76 versus 37 cases were compared for open surgery alone versus adjunctive MMAE following open surgery. Similarly, the adjunctive MMAE group had significantly lower rates of recurrence (5.4% vs 19.7%, p = 0.037) and overall reintervention (2.7% vs 14.5%, p = 0.049). CONCLUSIONS Adjunctive MMAE following open surgery can lower the recurrence risks and reintervention rates for cSDH.

OBJECTIVE Middle meningeal artery (MMA) embolization (MMAE) is a new therapeutic modality for chronic subdural hematoma (cSDH). There is limited evidence comparing various MMAE procedural techniques, resulting in significant variations in technique and procedural planning. The objective of this study was to compare outcomes of MMAE by the number and location of MMA branches that were embolized. METHODS A single-center retrospective study of patients with cSDH treated by MMAE was conducted. Clinical outcomes, need for re-intervention, and changes in hematoma size were compared between different MMAE techniques. RESULTS Ninety-four cSDHs in 78 patients were included. Embolization of the proximal trunk only, distal branches only, or proximal trunk plus distal branches resulted in similar rates of need for rescue surgery (7.4%, 13.0%, and 6.8%, respectively; p = 0.66) and rates of reducing the volume of the hematoma by at least 50% (74.1%, 80.0%, and 77.5%, respectively; p = 0.88). Embolization of only one branch had similar outcomes to embolization of more than one branch, as rescue surgery rates were 9.3% and 7.8% (p = 0.80), and rates ≥ 50% volume reduction were 75.6% and 78.3% (p = 0.76), respectively. Selective embolization of the dominant MMA branch was not associated with significantly different outcomes. CONCLUSIONS Outcomes of distal, proximal, or combined proximal and distal MMAE in cSDH are not significantly different. Embolization of more than one branch is not associated with improved treatment efficacy. Arguably, targeting any location in the MMA provides sufficient flow restriction to enable spontaneous hematoma resolution. Accordingly, a technical planning algorithm for cSDH MMAE is suggested.

OBJECTIVE Unruptured intracranial aneurysms are frequently detected during routine clinical diagnostic processes. A significant portion are small aneurysms less than 5 mm in diameter. While follow-up of patients with small aneurysms has been advocated, the cost-effectiveness of such care and the optimal follow-up interval remain unknown. This study aimed to explore the most cost-effective follow-up interval for small (< 5 mm) unruptured intracranial aneurysms. METHODS A decision analysis study was performed using a Markov model with Monte Carlo simulations to simulate patients undergoing follow-up by MRA at different time intervals (1-, 2-, 3-, 5-, and 7-year intervals) for small (< 5 mm) unruptured intracranial aneurysms. Input data for the model were extracted from the current literature, primarily meta-analyses. Probabilistic and deterministic sensitivity analyses were performed to evaluate the robustness of the model. RESULTS Given the current literature and the model in this study, following up every 2 years with noninvasive imaging is the most cost-effective strategy (cost $126,996, effectiveness 21.9 quality-adjusted life-years), showing the highest net monetary benefit. The conclusion remains robust in probabilistic and deterministic sensitivity analyses. As the annual growth risk of small aneurysms and annual rupture risk of growing aneurysms increase, following up every year is optimal. When the cost for follow-up with MRA is less than $2223, following up every year is cost-effective. CONCLUSIONS The most cost-effective follow-up strategy for small (< 5 mm) unruptured aneurysms using MRA is following up every 2 years. More frequent follow-up strategies or prompt preventive treatment would be more appropriate in patients with higher risk factors for growth and aneurysm rupture.

Genome-wide association studies (GWAS) have markedly advanced our understanding of the genetics of Parkinson’s disease (PD), but they currently do not account for the full heritability of PD. In many cases it is difficult to unambiguously identify a specific gene within each locus because GWAS does not provide functional information on the identified candidate loci. Here we present an integrative approach that combines transcriptome-wide association study (TWAS) with high-throughput neuronal dysfunction analyses in Drosophila to discover and validate candidate PD genes. We identified 160 candidate genes whose misexpression is associated with PD risk via TWAS. Candidates were validated using orthogonal in silico methods and found to be functionally related to PD-associated pathways (i.e. endolysosome). We then mimicked these TWAS-predicted transcriptomic alterations in a Drosophila PD model and discovered that 50 candidates can modulate α-Synuclein(α-Syn)-induced neurodegeneration, allowing us to nominate new genes in previously known PD loci. We also uncovered additional novel PD candidate genes within GWAS suggestive loci (e.g. TTC19, ADORA2B, LZTS3, NRBP1, HN1L), which are also supported by clinical and functional evidence. These findings deepen our understanding of PD, and support applying our integrative approach to other complex trait disorders.

Introduction: Emergency medical services (EMS) were designed to prevent death and disability. When hospice patients call 9-1-1, it can create challenging scenarios for EMS providers, patients, and families. The objective of this investigation is to understand the characteristics of hospice and comfort care patient EMS utilization in Alameda County, California. Methods: This is a 15-month (7/1/2019-10/1/2020) retrospective observational study in Alameda County using electronic patient care reports (PCRs). The search terms "hospice" and "comfort measures only" were applied to PCR narratives. Results: Of the 237,493 EMS provider response calls, 534 (0.2%) were for hospice and comfort care patients. One hundred seventy-four (32.6%) calls were from skilled nursing facilities versus 343 (64.2%) from private residences. Among the most common primary impressions were respiratory complaints (96; 18.0%), altered mental status (96; 18.0%), weakness (58; 10.9%), and cardiac arrest (45; 8.4%). The most common interventions included blood glucose (244; 45.7%), electrocardiogram (181; 33.9%), and intravenous placement (170; 31.8%). Of note, eight (1.5%) patients received cardiopulmonary resuscitation, and an additional eight (1.5%) patients were intubated endotracheally or received a supraglottic airway device for intubation. Sixty-eight (12.7%) patients received medications, the most common of which were fentanyl (17; 3.2%) and albuterol (16; 3.0%). Of note, five (0.9%) patients received naloxone. Ultimately, 468 (87.6%) patients were transported by EMS. Of the 33 (6.1%) patients who died on the scene, three received resuscitation attempts. Conclusion: Although EMS providers encounter hospice and comfort care patients infrequently, awareness of hospice services and comprehensive end-of-life care communication skills with patients and family should be an important part of EMS.

Tocilizumab is one of few treatments that have been shown to improve mortality in patients with coronavirus disease 2019 (COVID-19), but increased demand has led to relative global shortages. Recently, it has been suggested that lower doses, or fixed doses, of tocilizumab could be a potential solution to conserve the limited global supply while conferring equivalent therapeutic benefit to the dosing regimens studied in major trials. The relationship between tocilizumab dose, exposure, and response in COVID-19 has not been adequately characterized. There are a number of pharmacokinetic (PK) parameters that likely differ between patients with severe COVID-19 and patients in whom tocilizumab was studied during the US FDA approval process. Likewise, it is unclear whether a threshold exposure is necessary for tocilizumab efficacy. The safety and efficacy of fixed versus weight-based dosing of tocilizumab has been evaluated outside of COVID-19, but it is uncertain if these observations are generalizable to severe or critical COVID-19. In the current review, we consider the potential advantages and limitations of alternative tocilizumab dosing strategies. Leveraging PK models and simulation analyses, we demonstrate that a fixed single dose of tocilizumab 400 mg is unlikely to produce PK exposures equivalent to those achieved in the REMAP-CAP trial, although weight-stratified dosing appears to produce more uniform exposure distribution. Data from current and future trials could provide PK/pharmacodynamic insight to better inform dosing strategies at the bedside. Ultimately, rational dosing strategies that balance available limited supply with patient needs are required.

Background Area under the curve (AUC)-guided monitoring of vancomycin for the treatment of Staphylococcus aureus (SA) infections demonstrates reduced rates of nephrotoxicity in clinical studies. Many institutions utilize AUC-guided dosing for all patients receiving vancomycin, despite extrapolated AUC goals for non-SA infections. We sought to define risk factors for vancomycin-induced kidney injury (VIKI) in non-SA infections. Methods This was a retrospective, single-center, case-control study evaluating risk factors associated with VIKI in hospitalized patients receiving AUC-guided dosing for non-SA infections from 2/2019-10/2021. Cases were defined as patients with non-SA infections who received >72 hours of vancomycin and had >1 observed vancomycin concentration with a corresponding AUC calculated who developed VIKI within 24 hours of vancomycin discontinuation. Controls had to meet all case criteria but did not have VIKI. Univariate and multivariable analyses were used to identify risk factors associated with VIKI. Multivariable analyses were conducted using the Optimal Data Analysis package for R. Results Twenty-three cases and 48 controls were included. Leading indications were bloodstream (52.1%) and severe skin/skin structure (46.5%) infections. Isolated pathogens from culture included coagulase-negative Staphylococcus (49.3%) and Streptococcus spp. (43.7%). The majority of vancomycin AUCs (52%) were collected within 24-48 hours of initiation. The median first and second AUCs were higher in cases vs. controls [429 vs. 385 mg*hr/L, p=0.013; and 573 vs. 429 mg*hr/L, p=0.021], respectively. Most patients (75%) experienced AKI within 72 hours of vancomycin initiation, with a median time to AKI of 5 days (IQR 2.5-7). Risk factors associated with AKI included any AUC exceeding 515 mg*hr/L, infection caused by pathogens other than Streptococcus spp., and non-bacteremia indications. Patients with AUCs exceeding 515 mg*hr/L had 3.7-fold greater odds of VIKI (p=0.017). Conclusion We found that higher AUCs increased the risk of VIKI in non-SA infections and that the risk of VIKI varied by vancomycin indication. Our findings agree with previous studies in SA indicating that vancomycin AUC should not generally exceed 515 mg*hr/L. Disclosures Nathaniel J. Rhodes, PharmD MS, Paratek: Grant/Research Support|Third Pole Therapeutics: Advisor/Consultant.

Background Obtaining scarce antimicrobials used to treat infrequently encountered infections such as malaria have posed a challenge to clinicians and health systems. Due to the rare occurrence of these infections, maintaining adequate, readily available supply for emergent need is challenging, and a lack of clear procurement processes from regional storage sites may contribute to delays in care. In March 2021, artesunate became commercially available for the treatment of severe malaria, a disease for which prompt initiation of therapy is paramount. To improve access to this and other critical but seldom used medications, a centralized storage and allocation process was established throughout our 10-hospital health system. We aim to describe the structure of this program which may serve as a model for other institutions to expedite and streamline access to these lifesaving therapies. Tracking document for therapy supply management. Methods In May 2021, a centralized process was created to track and store rare anti-infective medications for uncommon infections, including those caused by tropical, parasitic, and mycobacterial pathogens (Table 1). Supply is monitored and maintained by clinical pharmacists monthly to ensure adequate courses are available. When needed for a specific patient, infectious diseases physicians and pharmacists recommend therapy which triggers a request to the central pharmacy. Results Medications are stored at our large academic medical center (AMC), which manages these cases more routinely compared to other sites. Community hospitals within the health system are able to contact the AMC for prompt distribution of these medications when needed. Since its inception, we have deployed rare use anti-infective medications to partner facilities twice for severe malaria cases, which resulted in expedited receipt of therapy for critically ill patients. The time from therapy recommendation to medication administration was reduced from 12–24 hours to 2–6 hours. Conclusion This centralized rare anti-infective medication process expedites and streamlines access for critical therapeutic agents to ensure they are readily available when needed by limiting procurement/storage concerns. This model may be used as a framework for other medications for which timely administration, but rare use, is critical to patient care. Disclosures All Authors: No reported disclosures.

Background Up to 15% of hospitalized patients report a penicillin allergy, but most can tolerate a β-lactam (BL). Use of second-line non-BL antibiotics poses untoward health consequences. Assessing for true penicillin allergies includes penicillin skin testing (PST) and a direct amoxicillin challenge, each with their own limitations in hospitalized patients. For inpatients, a graded challenge (GC) with the desired BL offers a streamlined approach for many who could benefit from a first-line BL agent. In 2019, a hospital-wide BL Allergy Assessment and Clinical Pathway was implemented, including a BL GC protocol for low-risk patients. This study aimed to assess the safety of the GC procedure in hospitalized patients. Methods A retrospective, observational cohort study of adult inpatients who completed a GC procedure between Sept 2019 – Sept 2021 was conducted. Primary objective: determine the incidence of a significant hypersensitivity reaction from a BL GC. Secondary objectives: 1) determine the incidence of a non-hypersensitivity reaction and 2) identify antimicrobial stewardship interventions in those tolerant to a BL GC (e.g. antibiotic switch to a BL with completion of treatment course and de-labeling of penicillin allergy). Results Fifty-one patients completed a GC procedure. Most (78%) had a reported allergy to penicillin vs. other BL antibiotics. Reported allergic reactions stratified by risk for a serious hypersensitivity episode were: low/reaction > 10 yrs ago – 33%; moderate-high/reaction > 10 yrs ago – 47%, and moderate-high/reaction < 5 yrs ago – 19.6%. A PST prior to a GC was performed in 75% of patients. Common GC agents included amoxicillin-clavulanate (16%), amoxicillin (12%) and ceftriaxone (12%). One patient experienced a hypersensitivity reaction managed with diphenhydramine and another patient had a non-hypersensitivity reaction. Both cases were non-life-threatening. Of the 49 patients who tolerated a GC, 76% were switched to a BL with completion of treatment course, and 84% of documented penicillin allergies were de-labeled or clarified in the electronic medical record. Conclusion The GC procedure in our hospitalized patients was generally well tolerated including those with an allergy history concerning for a moderate-high risk hypersensitivity reaction. Disclosures Nathaniel J. Rhodes, PharmD, MSc, American Academy of Colleges of Pharmacy: Grant/Research Support|Paratek: Grant/Research Support|Third Pole Therapeutics: Advisor/Consultant Marc H. Scheetz, PharmD, MSc, Abbvie: Advisor/Consultant|Allecra: Grant/Research Support|Merck: Advisor/Consultant|Nevakar: Advisor/Consultant|Nevakar: Grant/Research Support|Premier Healthcare Solutions: Honoraria|Spero: Advisor/Consultant|SuperTrans Medical: Advisor/Consultant|SuperTrans Medical: Grant/Research Support|Takeda: Advisor/Consultant|Third Pole Therapeutics: Advisor/Consultant.

In this case series of twenty ambulatory and hospitalized adult patients treated for monkeypox virus at a large academic medical center in Chicago, Illinois, tecovirimat use was reserved for those with or at high risk of severe disease, delayed due to logistical and clinical factors, but well tolerated.

Objective: Engaging youth in planning, developing, and implementing substance misuse prevention efforts can improve those efforts. However, specific local policies and systems constrain youth engagement practice. This study examines how to engage youth in substance misuse prevention within state prevention systems. Methods: In the qualitative study, semi-structured interviews with 13 prevention providers in the North Carolina prevention system were conducted via video call and transcribed and analyzed via thematic and codebook approaches. Procedures are reported according to the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. Results: Providers viewed youth engagement favorably yet mostly did not differentiate between youth-targeted prevention initiatives and youth-engaged initiatives. Findings reveal how state-level decisions, such as definitions and funding policies, support and challenge how providers implement youth engagement. Conclusions: To encourage youth engagement, state prevention systems should clarify for providers the distinction between prevention efforts targeted to youth and those that engage youth in planning and implementing and define which activities are desirable and what the role of youth should be in the activities. Finally, prevention providers need support for youth-engaged approaches to prevention, specifically training for youth and adult allies and opportunities for knowledge-sharing.

Disclaimer In an effort to expedite the publication of articles , AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Linezolid and daptomycin resistance among Enterococccus faecium (Efm) isolates, while rare, is a major challenge for clinicians who are often limited to broad-spectrum or combination antibiotic therapies for management. Combination therapy with a beta-lactam has been reported, but limited clinical evidence exists to support its use. We describe the clinical management of a prolonged Efm intraabdominal (IA) infection and subsequent bacteremia, along with observed multidrug resistance development and use of serial whole genome sequencing to better understand resistance mechanisms. Combination antimicrobial therapy with daptomycin (DAP) and ceftaroline (CPT) was used to treat the patient’s catheter-associated daptomycin-, linezolid-, vancomycin-resistant Efm (DLVRE) bloodstream infection. In vitro antimicrobial testing of this DLVRE revealed only minor synergy between daptomycin and ceftaroline; However, the patient’s bacteremia cleared following initiation of combination therapy in conjunction with catheter removal. Sequencing of the patient’s DLVRE revealed multiple genomic mutations which explain both linezolid and daptomycin resistance and the presence of a plasmid containing known resistance determinants for vancomycin. Daptomycin resistance was attributed to the presence of chromosomal mutations in liaS (Thr120Ala), liaR (Trp73Cys), and cls (Asp13Ile), while linezolid resistance was attributed to the presence of the G2576T variant allele in some of 23S rRNA gene copies. Sequential whole genome sequencing of two additional bacterial isolates from the same patient revealed protracted colonization with a single DLVRE clone and suggested the development of bacterial subpopulations. Pairing clinical isolate susceptibilities with whole genome sequencing should be encouraged in clinical practice to better inform antimicrobial management in cases of multidrug resistance.

Purpose The coronavirus disease 2019 (COVID-19) pandemic has impacted the activities of healthcare workers, including postgraduate pharmacy trainees. Quality training experiences must be maintained to produce competent pharmacy practitioners and maintain program standards. Methods A cross-sectional survey of postgraduate pharmacy trainees in the United States was conducted to evaluate training experience changes and assess perceived impacts on residents and fellows following the COVID-19 pandemic’s onset. Results From June 4 through June 22, 2020, 511 pharmacy trainees in 46 states completed the survey. Participants’ median age was 26 (interquartile range [IQR], 25-28) years, with included responses from postgraduate year 1 residents (54% of sample), postgraduate year 2 residents (40%), and postgraduate fellows (6%). Compared to experiences prior to the onset of the COVID-19 pandemic, fewer trainees conducted direct patient care (38.5% vs 91.4%, P < 0.001), more worked from home (31.7% vs 1.6%, P < 0.001), and less time was spent with preceptors per day (2 [IQR, 2-6] hours vs 4 [IQR, 1-4] hours, P < 0.001). Sixty-five percent of respondents reported experiencing changes in their training program, 39% reported being asked to work in areas outside of their routine training experience, and 89% stated their training shifted to focus on COVID-19 to some degree. Most respondents perceived either major (9.6%) or minor (52.0%) worsening in quality of experience, with major and minor improvement in quality of experience reported by 5.5% and 8.4% of respondents, respectively. Conclusion Pharmacy resident/fellow experiences were perceived to have been extensively impacted by the COVID-19 pandemic in varying ways. Our findings describe shifts in postgraduate training and may aid in the development of best practices for optimizing trainee experiences in future crises.

Background Vancomycin (VAN)-associated acute kidney injury (AKI) is increased when VAN is combined with certain beta-lactams (BLs) such as piperacillin-tazobactam (TZP) but has not been evaluated with ceftolozane-tazobactam (C/T). Our aim was to investigate the AKI incidence of VAN in combination with C/T (VAN/C/T) compared with VAN in combination to TZP (VAN-TZP). Methods We conducted a multicenter, observational, comparative study across the United States. The primary analysis was a composite outcome of AKI and risk, injury, failure, loss, end stage renal disease; Acute Kidney Injury Network; or VAN-induced nephrotoxicity according to the consensus guidelines. Multivariable logistic regression analysis was conducted to adjust for confounding variables and stratified Kaplan–Meir analysis to assess the time to nephrotoxicity between the 2 groups. Results We included VAN/C/T (n = 90) and VAN-TZP (n = 284) at an enrollment ratio of 3:1. The primary outcome occurred in 12.2% vs 25.0% in the VAN-C/T and VAN-TZP groups, respectively (P = .011). After adjusting for confounding variables, VAN-TZP was associated with increased odds of AKI compared with VAN-C/T; with an adjusted odds ratio of 3.308 (95% confidence interval, 1.560–6.993). Results of the stratified Kaplan–Meir analysis with log-rank time-to-nephrotoxicity analysis indicate that time to AKI was significantly shorter among patients who received VAN-TZP (P = .004). Cox proportional hazards analysis demonstrated that TZP was consistent with the primary analysis (P = .001). Conclusions Collectively, our results suggest that the AKI is not likely to be related to tazobactam but rather to piperacillin, which is a component in VAN-TZP but not in VAN-C/T.

Backgroundand Purpose: Cerebral venous thrombosis (CVT) is a rare cause of stroke carrying a nearly 4% risk of recurrence after 1 year. There is limited data on predictors of recurrent venous thrombosis in patients with CVT. In this study, we aim to identify those predictors.Methods:This is a secondary analysis of the ACTION-CVT study which is a multi-center international study of consecutive patients hospitalized with a diagnosis of CVT over a 6-year period. Patients with cancer associated CVT, CVT during pregnancy, or CVT in the setting of known antiphospholipid antibody syndrome were excluded per the ACTION-CVT protocol. The study outcome was recurrent venous thrombosis defined as recurrent venous thromboembolism (VTE) or de-novo CVT. We compared characteristics between patients with vs. without recurrent venous thrombosis during follow-up and performed adjusted Cox regression analyses to determine important predictors of recurrent venous thrombosis.Results:947 patients were included with a mean age was 45.2 years, 63.9% were women, and 83.6% had at least 3-months of follow-up. During a median follow-up of 308 (IQR 120-700) days, there were 5.05 recurrent venous thromboses (37 VTE and 24 de-novo CVT) per 100 patient-years. Predictors of recurrent venous thrombosis were Black race (adjusted HR 2.13, 95% CI 1.14-3.98, p = 0.018), prior history of VTE (aHR 3.40, 95% CI 1.80-6.42, p < 0.001) and the presence of one or more positive antiphospholipid antibodies (aHR 3.85, 95% CI 1.97-7.50, p < 0.001). Sensitivity analyses including events only occurring on oral anticoagulation yielded similar findings.Conclusion:Black race, history of VTE, and the presence of one or more antiphospholipid antibodies are associated with recurrent venous thrombosis among patients with CVT. Future studies are needed to validate our findings to better understand mechanisms and treatment strategies in patients with CVT.

Background: A small randomized controlled trial suggested that dabigatran may be as effective as warfarin in the treatment of cerebral venous thrombosis (CVT). We aimed to compare direct oral anticoagulants (DOACs) to warfarin in a real-world CVT cohort. Methods: This multicenter international retrospective study (United States, Europe, New Zealand) included consecutive patients with CVT treated with oral anticoagulation from January 2015 to December 2020. We abstracted demographics and CVT risk factors, hypercoagulable labs, baseline imaging data, and clinical and radiological outcomes from medical records. We used adjusted inverse probability of treatment weighted Cox-regression models to compare recurrent cerebral or systemic venous thrombosis, death, and major hemorrhage in patients treated with warfarin versus DOACs. We performed adjusted inverse probability of treatment weighted logistic regression to compare recanalization rates on follow-up imaging across the 2 treatments groups. Results: Among 1025 CVT patients across 27 centers, 845 patients met our inclusion criteria. Mean age was 44.8 years, 64.7% were women; 33.0% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times. During a median follow-up of 345 (interquartile range, 140–720) days, there were 5.68 recurrent venous thrombosis, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years. Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization. When compared with warfarin, DOAC treatment was associated with similar risk of recurrent venous thrombosis (aHR, 0.94 [95% CI, 0.51–1.73]; P =0.84), death (aHR, 0.78 [95% CI, 0.22–2.76]; P =0.70), and rate of partial/complete recanalization (aOR, 0.92 [95% CI, 0.48–1.73]; P =0.79), but a lower risk of major hemorrhage (aHR, 0.35 [95% CI, 0.15–0.82]; P =0.02). Conclusions: In patients with CVT, treatment with DOACs was associated with similar clinical and radiographic outcomes and favorable safety profile when compared with warfarin treatment. Our findings need confirmation by large prospective or randomized studies.

Two proposition 65 no-significant-risk level (NSRL)-type values were derived for 2-nitropropane (2-NP), in the absence of a Californian published NSRL. In addition, a safety assessment was performed based on estimated typical consumer inhalation and dermal exposure to 2-NP during indoor application of paint from a spray can containing the solvent 1-nitropropane. For the NSRL derivation, benchmark dose (BMD) modeling was performed using hepatocellular carcinoma incidence data from 2-NP single exposure inhalation studies in Sprague-Dawley rats. Several BMD models provided an acceptable fit for the male rat hepatocellular carcinoma incidence data (gamma, log-probit, log-logistic and multistage); therefore, the mean of the BMD lower limits from each model were used as the point of departure to derive the inhalation cancer potency. The oral human cancer potency was derived from the inhalation human cancer potency based on the ratio of the uptake factors for inhalation vs. oral routes. The derived inhalation and oral NSRLs are 67 μg/day and 32 μg/day, respectively. For the inhalation and dermal exposure assessment, three key factors were analyzed: the 2-NP residual concentration in the spray paint product, the mass of spray paint used and the frequency of use. Based on the screening exposure assessment, potential consumer inhalation and dermal exposure to 2-NP from indoor application of paint from a spray can does not exceed our proposed NSRLs, and a warning label is therefore not required for spray can products containing the solvent 1-nitropropane where 2-NP is a minor contaminant.

Clinicians, researchers, and the public frequently turn to digital channels and social media for up-to-the-minute information on novel therapeutics and vaccines. The value of credible infectious diseases drug information is more apparent in the setting of the coronavirus disease 2019 (COVID-19) pandemic. This viewpoint by the Society of Infectious Diseases Pharmacists (SIDP) provides guidance on utilizing social media platforms to optimize infectious diseases pharmacotherapy. It includes tips for all levels of users but primarily serves a guide for the infectious diseases clinician who has not yet joined social media. It compares various social media platforms and suggests which to begin with based on user needs, recommends efficient curation of social media content, and outlines a stepwise approach (shown below) to increasing engagement over time. This summary will hopefully spur further quality content and engagement regarding drug information from the infectious diseases social media network.

Disparities in access to anti-SARS-CoV-2 monoclonal antibodies have not been well characterized.We sought to explore the impact of race/ethnicity as a social construct on monoclonal antibody delivery.Following implementation of a centralized infusion program at a large academic healthcare system, we reviewed a random sample of high-risk ambulatory adult patients with COVID-19 referred for monoclonal antibody therapy.We examined the relationship between treatment delivery, race/ethnicity, and other demographics using descriptive statistics, binary logistic regression, and spatial analysis.There was no significant difference in racial composition between patients who did (n = 25) and patients who did not (n = 378) decline treatment (p = 0.638). Of patients who did not decline treatment, 64.8% identified as White, 14.8% as Hispanic/Latinx, and 11.1% as Black. Only 44.6% of Hispanic/Latinx and 31.0% of Black patients received treatment compared to 64.1% of White patients (OR 0.45, 95% CI 0.25-0.81, p = 0.008, and OR 0.25, 95% CI 0.12-0.50, p0.001, respectively). In multivariable analysis including age, race, insurance status, non-English primary language, county Social Vulnerability Index, illness severity, and total number of comorbidities, associations between receiving treatment and Hispanic/Latinx or Black race were no longer statistically significant (AOR 1.32, 95% CI 0.69-2.53, p = 0.400, and AOR 1.34, 95% CI 0.64-2.80, p = 0.439, respectively). However, patients who were uninsured or whose primary language was not English were less likely to receive treatment (AOR 0.16, 95% CI 0.03-0.88, p = 0.035, and AOR 0.37, 95% CI 0.15-0.90, p = 0.028, respectively). Spatial analysis suggested decreased monoclonal antibody delivery to Cook County patients residing in socially vulnerable communities.High-risk ambulatory patients with COVID-19 who identified as Hispanic/Latinx or Black were less likely to receive monoclonal antibody therapy in univariate analysis, a finding not explained by patient refusal. Multivariable and spatial analyses suggested insurance status, language, and social vulnerability contributed to racial disparities.

Background and Purpose: Epidemiological studies have shown racial and ethnic minorities to have higher stroke risk and worse outcomes than non-Hispanic Whites. In this cohort study, we analyzed the STAR (Stroke Thrombectomy and Aneurysm Registry) database, a multi-institutional database of patients who underwent mechanical thrombectomy for acute large vessel occlusion stroke to determine the relationship between mechanical thrombectomy outcomes and race. Methods: Patients who underwent mechanical thrombectomy between January 2017 and May 2020 were analyzed. Data included baseline characteristics, vascular risk factors, complications, and long-term outcomes. Functional outcomes were assessed with respect to Hispanic status delineated as non-Hispanic White (NHW), non-Hispanic Black (NHB), or Hispanic patients. Multivariate analysis was performed to identify variables associated with unfavorable outcome or modified Rankin Scale ≥3 at 90 days. Results: Records of 2115 patients from the registry were analyzed. Median age of Hispanic patients undergoing mechanical thrombectomy was 60 years (72–84), compared with 63 years (54–74) for NHB, and 71 years (60–80) for NHW patients ( P P P P Conclusions: Hispanic patients are less likely to have favorable outcome at 90 days following mechanical thrombectomy compared to NHW or NHB patients. Further prospective studies are required to validate our findings.

Tocilizumab is one of few treatments that have been shown to improve mortality in patients with COVID-19, but increased demand has led to relative global shortages. Recently, it has been suggested that lower doses, or fixed doses, of tocilizumab could be a potential solution to conserve the limited global supply while conferring equivalent therapeutic benefit to the dosing regimens studied in major trials. The relationship between tocilizumab dose, exposure, and response in COVID-19 has not been adequately characterized. There are a number of pharmacokinetic (PK) parameters which likely differ between patients with severe COVID-19 and patients in whom tocilizumab was studied during the FDA approval process. Likewise, it is unclear whether a threshold exposure is necessary for tocilizumab efficacy. The safety and efficacy of fixed versus weight-based dosing of tocilizumab has been evaluated outside of COVID-19, but it is uncertain if these observations are generalizable to severe or critical COVID-19. In the current review, we consider the potential advantages and limitations of alternative tocilizumab dosing strategies. Leveraging PK models and simulation analyses, we demonstrate that a fixed single dose of tocilizumab 400 mg is unlikely to produce PK exposures equivalent to those achieved in the REMAP-CAP trial, though weight-stratified dosing appears to produce more uniform exposure distribution. Data from current and future trials could provide PK/PD insight to better inform dosing strategies at the bedside. Ultimately, rational dosing strategies that balance available limited supply with patient needs are required.

Hospitalized patients with community-acquired pneumonia (CAP) are at risk of developing Clostridioides difficile infection (CDI). We developed and tested clinical decision rules for identifying CDI risk in this patient population. The study was a single-center retrospective, case-control analysis of hospitalized adult patients empirically treated for CAP between 1 January 2014 and 3 March 2018. Differences between cases (CDI diagnosed within 180 days following admission) and controls (no test result indicating CDI during the study period) with respect to prehospitalization variables were modeled to generate propensity scores. Postadmission variables were used to predict case status on each postadmission day where (i) ≥1 additional case was identified and (ii) each model stratum contained ≥15 subjects. Models were developed and tested using optimal discriminant analysis and classification tree analysis. Forty-four cases and 181 controls were included. The median time to diagnosis was 50 days postadmission. After weighting, three models were identified (20, 117, and 165 days postadmission). The day 20 model yielded the greatest (weighted [w]) accuracy (weighted area under the receiver operating characteristic curve [wROC area] = 0.826) and the highest chance-corrected accuracy (weighted effect strength for sensitivity [wESS] = 65.3). Having a positive culture (odds, 1:4; P = 0.001), receipt of ceftriaxone plus azithromycin for a defined infection (odds, 3:5; P = 0.006), and continuation of empirical broad-spectrum antibiotics with activity against P. aeruginosa when no pathogen was identified (odds, 1:8; P = 0.013) were associated with CDI on day 20. Three models were identified that accurately predicted CDI in hospitalized patients treated for CAP. Antibiotic use increased the risk of CDI in all models, underscoring the importance of antibiotic stewardship.

Flow diverters are new generation stents that have recently garnered a large amount of interest for use in treatment of intracranial aneurysms. Flow diverters reduce blood flow into the aneurysm, with redirection along the path of the parent vessel. Flow stagnation into the aneurysm and neck coverage with subsequent endothelialization are the important synergistic mechanisms by which the therapy acts. Several studies have examined the mechanisms by which flow diverters subsequently lead to aneurysm occlusion. This review aims to provide a general overview of the flow diverters and their mechanism of action and potential implications. ANN NEUROL 2019;85:793-800.

Background Nosocomial acquisition of vancomycin-resistant Enterococcus (VRE) is one of the most challenging problems in healthcare. As Enterococcus isolates are increasingly resistant to vancomycin, clinicians now rely on alternative antimicrobial therapies including linezolid and daptomycin (DAP) to treat infections. For multidrug-resistant (MDR) VRE, combination therapy with beta-lactams and daptomycin has been shown to be effective. Methods Following initiation of empiric DAP and ceftaroline (CPT) for an MDR E. faecium bloodstream infection (VRE_001), we aimed to determine if there existed in vitro synergy between both agents that supported their clinical use. Combination synergy testing was performed using E-test strips and minimal inhibitory concentrations (MICs) were read at 24 hours. For whole genome sequence-based analysis (WGS), genomic DNA from VRE_001 was used for both short read (Illumina MiSeq) and long-read sequencing (MinION, Nanopore). The complete genome was assembled and the NCBI AMRFinderPlus program used to identify known resistance mechanisms. Results Original MICs of VRE_001 from the clinical microbiology laboratory at Northwestern Memorial revealed an MDR E. faecium (Table 1). Combination synergy testing in the experimental laboratory revealed only modest amounts of synergy between CPT and DAP (Table 2). Following WGS, VRE_001 was identified as an ST-584 E. faecium with a 3.2 Mbp genome, including a single chromosome and five plasmids. WGS analysis revealed several mechanisms of antimicrobial resistance (Table 3) genetically supporting the observed MDR-DLVRE phenotype. Conclusion Our investigational antimicrobial testing allowed for real-time in vitro analysis of synergistic MICs in a case of DLVRE bacteremia. Despite the fact that in vitro testing of CPT and DAP did not support the clinical usage of combination antimicrobial therapy, the patient cleared their blood cultures. WGS of VRE_001 revealed a plethora of antimicrobial resistance mechanisms including three mutations that explain high levels of DAP resistance. Synergy testing is not routinely available in most clinical laboratories, but rapid implementation of investigational MIC testing paired with genomic analysis may one day successfully support real-time clinical decision making. Disclosures All Authors: No reported disclosures