Comorbid Disease Burden Research Articles

P-1426. Comorbidities and Healthcare Resource Utilization Among People With HIV: Real-World Data From a Large Israeli Healthcare Provider

Abstract Background Despite recent advances in HIV antiretroviral treatment (ART), unmet needs for people with HIV (PWH) remain. The study compared comorbid disease burden and healthcare resource utilization (HRU) among PWH vs those without HIV diagnosis, as well as by ART patterns. Methods A retrospective cross-sectional study used anonymized electronic healthcare data from Israel’s Maccabi Healthcare Services (MHS; >2.7M members) to compare people living with HIV on 31/12/2022 with age-sex-matched controls without HIV diagnosis (1998−2022). PWH had to have ≥1 HIV diagnosis code(s) (1998−2022) and ≥1 dispensed ART prescription (2008−2022). Members enrolled for < 12 months were excluded. Sociodemographic characteristics, lifetime prevalence of comorbidities (exception: anxiety/depression, diagnosed and/or treated in 2022), and HRU (2022) were described. Among PWH dispensed ≥1 ART in 2022, patterns of 12-month percentage of days covered (PDC), discontinuation (≥90-day treatment gap), and interruption (resumed treatment after 6−89-day gap) were described. Results Among 1973 PWH and 9865 controls, mean±SD age was 48.2±11.2 and 48.7±11.2 years, respectively, and 74.4% were male. A lower proportion of PWH (39.6%) vs controls (48.0%) had high residential socioeconomic status. Higher prevalence of comorbidities among PWH vs controls included anxiety/depression (26.2% vs 13.5%), liver disease (20.9% vs 12.5%), chronic kidney disease (14.9% vs 7.3%), cancer (7.2% vs 5.3%), hepatitis C virus (5.6% vs 0.1%), and hepatitis B virus (HBV; 3.4% vs 0.4%). PWH (vs controls) had a median of 10 primary-care visits/year (vs 7) and more frequent hospital admissions (≥1: 11.4% vs 6.6%) and emergency room visits (≥1: 26.5% vs 19.0%). Among PWH treated in 2022 (n=1907), 78.1% had PDC ≥90%. Discontinuation and interruption occurred among 7.2% and 69.1% of treated PWH, respectively. PWH with PDC < 90% (vs ≥90%) had younger age, lower socioeconomic status, higher prevalence of HBV diagnosis, and less frequent physician visits in prior 12 months. Conclusion Despite high ART coverage, PWH in Israel experience an excess burden of comorbidities and HRU compared to age-sex-matched controls without HIV. Further research is needed to address the excess disease burden and better define treatment/care gaps among PWH. Disclosures Sivan Gazit, MD, AbbVie: The relationship is not personal, AbbVie funded the current study, funding to the research institution where I work Arlene Nugent, MSc, Abbvie: Stocks/Bonds (Public Company) Liza Bronner Murrison, PhD, AbbVie: Stocks/Bonds (Public Company) Ana Gabriela Pires dos Santos, PhD, ABBVIE: Stocks/Bonds (Public Company)

Alzheimer’s disease blood tests of amyloid‐beta 42/40, %p‐tau217, 181, and 205 ratios and MTBR‐243 in real‐world populations: Results from SEABIRD and BioFINDER2

AbstractBackgroundAlzheimer’s disease (AD) blood tests that can identify and quantify amyloid plaques, tau tangles, and cognitive and clinical decline are needed in clinical practice, including primary care. However, these tests require validation in diverse groups and real‐world settings. The Study to Evaluate Amyloid in Blood and Imaging Related to Dementia (SEABIRD) enrolled 1,122 participants to determine the accuracy and validity of AD blood biomarkers, including amyloid‐β (Aβ) and phosphorylated tau (p‐tau) tests, in a diverse, community‐based sample of older adults compared with amyloid PET and cognitive and clinical measures to determine the impact of key factors (age, race, education, cognition, APOE genotype, and medical conditions).MethodSEABIRD measured blood plasma Aβ42/40, %p‐tau217, %p‐tau181 and %p‐tau205 ratios by immunoprecipitation‐mass spectrometry. Measures of cognitive and clinical impairment included the AD8® dementia screen, Montreal Cognitive Assessment (MoCA), and the Clinical Dementia Rating (CDR®). 26% of participants completed amyloid PET for comparison to the blood tests. The novel plasma endogenous microtubule binding region of tau with 243 residue (E‐MTBR‐tau243) was measured in a separate cohort, the Swedish BioFINDER2 study, and compared to tau PET for tau tangle assessment.ResultOf the 1,122 participants enrolled in SEABIRD, 23.5% self‐identified as Black or African American and the percentage of APOE ε4 carriers was 32.1%, as expected for a general population (Table 1). The classification accuracy (ROC AUC) of plasma measures for amyloid PET status was evaluated in a subset of participants: Aβ42/40 0.88, %p‐tau217 ratio 0.96, %p‐tau181 ratio 0.79, and %p‐tau205 ratio 0.83 (Figure 1). The classification accuracy for tau PET status was evaluated in amyloid PET positive participants in BioFINDER2: plasma E‐MTBR‐tau243 0.98, %p‐tau217 ratio 0.87, p‐tau217 concentration 0.89 (Figure 2).ConclusionIn a diverse population with high comorbid disease burden, AD blood tests using ratios had similar accuracies to those reported in AD research cohorts. Our findings support the clinical use of these tests for detection of both amyloid and tau AD pathologies in the general population. Further, screening with AD blood tests can accelerate enrollment of more diverse cohorts into clinical trials, enabling treatments to demonstrate effectiveness in representative populations.

The nexus between Leishmania & HIV: Debilitating host immunity and Hastening Comorbid disease burden

The scintillating association between Leishmania and HIV has contributed exceptionally towards expansion of Visceral Leishmaniasis (VL) with Acquired Immunodeficiency Syndrome (AIDS). The co-infection poses a grievous threat to elimination of VL and containment of Human Immunodeficiency Virus (HIV). When coinfected, Leishmania and HIV complement each other's proliferation and survival by inducing immunesenescence, T cell fatigue and exhaustion. Antigen presentation is lost, co-stimulatory molecules are diminished whereas co-inhibitory molecules such as CTLA-4, TIGIT, LAG-3 etc. are upregulated to ensure a Th2-baised immune environment. As a consequence, Leishmania-HIV coinfection causes poor outcomes, inflates the spread of Leishmania parasites, enhances the severity of side-effects to drugs, as well as escalate the probability of treatment failure and mortality. What makes control extremely strenuous is that there are frequent episodes of VL relapse with no prognostic markers, no standard immunophenotype(s) and appearance of atypical clinical symptoms. Thus, a standard therapeutic regimen has been difficult to develop and treatment is majorly dependent upon a combination of liposomal Amphotericin B and Miltefosine, a therapy that is expensive and capable of causing drastic side-effects in recipients. As World Health Organization is committed to eliminate both VL and HIV in due course of future, the existing therapeutic interventions require advancements to grapple and overcome this hazardous co-infection. In this context, an overview of HIV-VL co-infection, immunopathology of HIV and Leishmania co-inhabitance, available therapeutic options and their limitations in the treatment of co-infection are discussed in-depth.

Distribution of neuropsychiatric profiles and comorbid diseases in dementia subtypes

Objectives: Alzheimer’s disease (AH) is the most prevalent cause of dementia, followed closely by vascular dementia. Mixed vascular-Alzheimer’s dementia (MVAD) is more evident in individuals aged 80 and above. Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after AH. Vascular risk factors play important role in the pathogenesis of dementia syndromes. Behavioral and psychological symptoms represent a significant portion of the non-cognitive manifestations in dementia patients. This study aimed to evaluate the distribution of chronic diseases, behavioral disorders, psychiatric findings, and medication use in patients followed with different dementia diagnoses. Methods: Prevalance of chronic diseases, behavioral disorders, psychiatric findings as well as the usage of antidepressant and antipsychotic medications among patients followed up in dementia outpatient clinics with the diagnosis of AD, mild cognitive impairment (MCI), vascular dementia (VaD), FTD, and MVAD were investigated. Neuropsychiatric inventory (NPI) was applied to the patients. Results: Four hundred and fifty-five patients were accepted in the study. The patients were distributed as follows: AD (n=303, female/male: 187/115, age = 78±8 years), MCI (n=53, female/male: 31/22, age = 69±10 years), VaD (n=31, female/male: 18/13, age = 68±9 years), FTD (n=32, female/male: 17/15, age = 68±9 years), and MVAD (n=36, female/male: 16/20, age = 76±10 years). Both AD and MVAD groups were significantly older than the other groups (F = 23.2, P<0.0001). The ratio of comorbid chronic diseases was 80% in the AD group, 72% in the MCI group, 91% in the VaD group, 59% in the FTD group, and 93% in the MVAD group. In the whole group, antipsychotic drug use was 27.5% and antidepressant drug use was 28.9%. The mean NPI score was 32.9±28 in antipsychotic users and 16±19 in non-users (P<0.0001). The mean NPI of antidepressant users was 17.6±19 and 21.9±25 (P=0.055) in non-users. Conclusion: There is a comorbid chronic disease burden in all dementia subtypes, although at varying intensities, and as the chronic disease burden increases, behavioral disorders and psychotic findings increase, and accordingly, the use of antipsychotics also increases.

The effects of anaesthesia and analgesia on short- and long-term outcomes following colorectal cancer surgery

BACKGROUND Colorectal cancer (CRC) is the second most frequent cause of global cancer mortality. Most patients with CRC require surgical tumour resection, with certain stages of CRC (Stage II/III) also requiring postoperative chemotherapy. The timing of postoperative chemotherapy is largely determined by postoperative recovery. Delayed return to intended oncologic therapy (RIOT) by >8 weeks results in worse oncologic outcomes. RIOT is thus an important surrogate marker of outcome for patients with stage II/III CRC. We will test the hypothesis that anaesthetic technique during CRC resection surgery may affect RIOT. OBJECTIVE To test the association between anaesthetic and analgesic technique during CRC surgery and RIOT. To document Short-term Secondary outcomes including individual postoperative complications and a composite of all postoperative complications, the Comprehensive Complications Index (CCI) and to measure the time to recurrence (TTR) of cancer at 3 years. DESIGN This is a prospective, international, multicentre, observational cohort study. SETTING Global healthcare setting, with >140 centres in >30 nations. PATIENTS Inclusion criteria: All patients age >18 years, ASA I–III, with CRC stage I–III scheduled for elective CRC surgery (open or minimally invasive). Exclusion criteria: Uncontrolled renal or liver disease, restrictive (limiting mobility) heart failure or ischemic heart disease (ASA IV–V). Speech, language, or cognitive difficulties precluding signing informed consent to participate and Stage IV CRC. PRIMARY OUTCOME MEASURES Short -term: The duration from day of surgery to RIOT among patients expected to receive postoperative chemotherapy. Long-term: incidence of recurrence and time to recurrence (TTR) at 3 years after primary curative surgery SECONDARY OUTCOMES Postoperative complications within 30 days of surgery, length of hospital stay, Days at Home at 30 and 90 days (DAH-30, DAH-90) after surgery, and adverse events related to oncological treatment. We will also assess the burden of preoperative modifiable comorbid disease in patients. Exploratory endpoints will assess practice variation (including incidence of RIOT by demographic e.g. gender of patient, type of institution, country). RESULTS N/A. CONCLUSIONS N/A. TRIAL REGISTRATION The Effects of aNesthesia in COloREctal cancer outcome study: ENCORE, ClinicalTrials.gov Identifier: NCT04493905.

Alzheimer’s disease blood tests of amyloid‐β 42/40, p‐tau217, p‐tau181 and p‐tau205 ratios in a diverse community‐based population: Preliminary results from SEABIR

AbstractBackgroundAlzheimer’s disease (AD) blood tests that can identify and quantify amyloid plaques, tau tangles, and cognitive and clinical decline are needed in clinical practice, including primary care. However, these tests require validation in diverse groups and real‐world settings. The goals of the Study to Evaluate Amyloid in Blood and Imaging Related to Dementia (SEABIRD) were to enroll 1120 participants to determine the accuracy and validity of blood amyloid‐β (Aβ) and phosphorylated tau (p‐tau) tests in a diverse, community‐based sample of older adults compared with amyloid PET, and to explore the impact of key factors (age, race, years of education, cognition, APOE genotype, and medical conditions) on validity estimates.MethodSEABIRD measured blood plasma Aβ42/40 ratio and ratios of phosphorylated to non‐phosphorylated p‐tau217, p‐tau181, and p‐tau205 (%p‐tau) in a diverse population of older adults. In addition, cognitive screening with the AD8® dementia screen and Montreal Cognitive Assessment (MoCA) were obtained. Approximately 25% of participants were selected for amyloid PET and CDR as a reference standard.ResultOf the 859 participants enrolled in this ongoing study, 20.6% self‐identified as Black or African American and the percentage of APOE ε4 carriers was 30.2%, as expected for a population‐based sample (Table 1). For a subset of 76 participants with completed amyloid PET and all blood measures, plasma Aβ42/40 had ROC‐AUC with amyloid PET status of 0.85, %p‐tau217 of 0.97, %p‐tau181 of 0.83, and %p‐tau205 of 0.81 (Figure 1). Spearman correlations with amyloid PET SUVR were ‐0.59 for plasma Aβ42/40, 0.69 for p‐tau217 ratio, 0.43 for p‐tau181 ratio and 0.48 for p‐tau205 ratio.ConclusionThese preliminary results demonstrate that AD blood tests have similar accuracies in a diverse population‐based sample to those reported in AD research cohorts. These findings suggest that rapid screening and diagnosis of amyloid pathology with AD blood tests is possible in a broader population with higher comorbid disease burden and greater diversity than typical AD research cohorts. Screening with AD blood tests could accelerate clinical trial recruitment and increase the representativeness of clinical trial populations, which may improve the generalizability of clinical trial results.

51 Trajectories and Predictors of Cognitive Change Following COVID-19

Objective:Acute cognitive complications following COVID-19 infection have been appreciated in a subset of patients since the early months of the global pandemic. Emerging data reveal that some patients go on to experience cognitive improvement, whereas others may experience further cognitive decline. We aimed to assess trajectories and predictors of cognitive change in a sample of post-COVID-19 patients.Participants and Methods:This prospective cohort study assessed longitudinal cognitive change in adults receiving care for COVID-19 in the Johns Hopkins Post-Acute COVID-19 Team (JH PACT) clinic. Participants self-administered the Digital Automated Neurobehavioral Assessment (DANA) battery of seven cognitive tests and a performance-based measure of cognitive fatigue on up to six occasions over six weeks. Improvement or decline between the first and last assessment was defined as change of >1 standard deviation of the baseline mean of each outcome. Potential predictors of change included demographic features (age, sex, race/ethnicity, education), COVID-19 illness characteristics (hospitalization or ICU stay, months since symptom onset), and comorbid disease burden. Analyses included measures of central tendency, independent samples t-tests, and chi-square tests of independence.Results:Of the 36 enrolled participants, 29 (81%) completed at least one DANA assessment (M = 4.7 assessments, SD = 1.8). Those completing at least three assessments (n = 24, 66.7%) were included in the present analyses (71% female; 58% white; M age = 54 years, SD = 10.9; M education = 14.6 years, SD = 2.4; M months since COVID-19 symptom onset at recruitment = 9.8, SD = 4.7; M comorbidities = 2.8, SD = 2.0). Fatigue was the most frequently improved outcome measure, with 41.7% of participants scoring >1 standard deviation above the baseline mean fatigue score at their final assessment. Among cognitive outcomes, the greatest frequency of improvement was observed on tests assessing rapid spatial processing (37.5%), processing speed (33.3%), and memory (33.3%). There were no consistent predictors of improvement, but several subtest-specific findings emerged. Specifically, (a) more comorbidities were positively associated with rate of fatigue reduction (p = .04), (b) longer duration since COVID-19 illness was positively associated with rates of memory improvement (p = .02), (c) older age, male sex, and more comorbidities were positively associated with rate of improvement in reaction time (ps < .05), and (d) more assessments completed was positively associated with rates of improvements in working memory (ps < .05). Response inhibition (12.5%), simple reaction times (16.7%), and working memory (16.7%) showed the lowest rates of improvement over time. Declines in cognition were infrequent, with 4.2 - 8.3% (n = 1 to 2) declining on measures of procedural reaction time, spatial processing, inhibitory control, or working memory.Conclusions:At an average of >9 months following acute COVID-19 illness, we observed longitudinal improvements in cognitive fatigue as well as processing speed, memory, and spatial reasoning. Consistent predictors of recovery were not identified, although age, sex, comorbid conditions, and time since illness predicted rates of improvement in select domains. Further analyses with a larger sample size and more stringent analyses are needed to confirm and extend these findings.

Effect of chronic antiplatelet therapy on clinical outcomes of endovascular thrombectomy for treatment of acute ischemic stroke.

The objective of this study was to investigate the prognostic significance of chronic antiplatelet therapy (APT) usage in acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT). Long-term APT may enhance recanalization but may also predispose patients to an increased risk of hemorrhagic transformation. Weighted hospitalizations for anterior-circulation AIS treated with EVT were identified in a large United States claims-based registry. Baseline clinical characteristics and outcomes were compared between patients with and without chronic APT usage prior to admission. Multivariable logistic regression analysis was performed to assess adjusted associations between APT and study endpoints. This analysis identified 36,560 patients, of whom 8170 (22.3%) were on a chronic APT regimen prior to admission. These patients were older and demonstrated a higher burden of comorbid disease, but had similar stroke severity on presentation in comparison with those not on APT. On unadjusted analysis, patients with prior APT demonstrated higher rates of favorable outcomes (24.3% vs 21.5%, p < 0.001), lower rates of mortality (7.0% vs 10.1%, p < 0.001), and lower rates of any intracranial hemorrhage (ICH; 20.3% vs 24.2%, p < 0.001), but no difference in rates of symptomatic ICH (sICH). Following multivariable adjustment for baseline clinical characteristics including age, acute stroke severity, and comorbidity burden, prior APT was associated with favorable outcome (adjusted odds ratio [aOR] 1.21, 95% CI 1.17-1.24, p < 0.001) and a lower likelihood of mortality (aOR 0.73, 95% CI 0.70-0.77, p < 0.001), without an increased likelihood of ICH (any ICH aOR 0.84, 95% CI 0.81-0.87, p < 0.001; sICH aOR 0.92, 95% CI 0.82-1.03, p = 0.131). Retrospective evaluation of patients with AIS treated with EVT using registry-based data demonstrated an association of prior APT usage with favorable outcomes, without an increased risk of hemorrhagic transformation.

Changing trends in the prevalence of heart failure impairment with Thalassemias over three decades.

To assess the prevalence trend and contributing factors of heart failure (HF) impairment with thalassemias at global, regional and national levels. Data on HF impairment with thalassemias was collected from the Global Burden of Disease study. The absolute number and prevalence of the disease were systematically collected for each year, and the estimated annual percentage changes (EAPC) in HF impairment were calculated by gender, region and country to measure temporal trends. Thalassemias have caused a significant global burden since 1990, and the case number of HF related to thalassemias has been steadily increasing. The highest case number of HF impairments with thalassemias is observed in China (7739 cases) and the highest prevalence is in Pakistan (1.61 per 100,000) currently. Besides, the middle sociodemographic index (SDI) region carries the highest burden of comorbid disease yet exhibits the most evident trend for improvement across the five regions (EAPC = -.98). The burden of thalassemias and comorbid HF is generally higher in males than females with the gender gap growing chasm in the future. Besides, the hotspots of HF impairment with thalassemias have gradually shifted to low SDI regions, though middle SDI regions still hold a relatively higher prevalence (.37 per 100,000) across different regions. The burden of thalassemias and accompanying HF, as well as their temporal trends, vary greatly across countries and regions. These findings can improve understanding of these conditions and guide policymakers in developing appropriate policies to address disparities between countries.

Mortality in elderly hemodialysis patients, influence of frailty and comorbidity

Background: Mortality in end-stage kidney disease (ESKD) remains high, especially among the elderly with a higher burden of comorbidity and frailty. In this group, dialysis may not offer better survival compared to conservative management. Frailty defined by clinical frailty scale (CFS) and comorbidity by Charlson Comorbidity Index (CCI) are known independent predictors of mortality. Our aim was to compare which one had higher impact on early mortality in urgent-start hemodialysis patients. Methods: We conducted a retrospective cohort study of patients aged 65 years and over, who started hemodialysis as their first renal replacement therapy (RRT) between January 2014 and December 2020. CFS and mCCI, at time of HD start, were used to evaluate, respectively, frailty and comorbid disease burden. The primary outcome was death in the first 6 months of RRT. Results: During the study period 166 patients were included. The median age, at time of hemodialysis start, was 75 years ± 6.3 years. The mortality at 6 months was 19% (n=31). For both scales, the analysis of ROC curve, stablished the optimal cut-off to predict the event death at first 6 months as ≥ 5points. The performance of CFS was superior to the mCCI, in fact, the area under the curve was significantly higher in CFS (0.739) versus the mCCI (0.620). A CFS≥5 had a sensitivity/specificity of 94%/44% in prediction the primary outcome. On the other hand, a mCCI≥5 predicts the same outcome with a sensitivity/specificity of 26%/88%. The diagnostic odds ratio for CFS≥5 was 11.6, compared to only 2.7 for mCCI≥5. Lastly, we constructed a model in which both scores interacted (as categorical variables), which after multivariable adjustment showed that mCCI/CFS &lt;5/≥5 and ≥5/≥5 were independent predictors of mortality (HR=7.06; P=0.017; HR=10.708; P=0.002; respectively). Interestingly, no events were observed in the mCCI≥5/CFS&lt;5 group. Conclusions: In this cohort of urgent-start incident HD patients, frailty defined by CFS was a stronger predictor of mortality than comorbidity defined by CCI.

Impact of Comorbid Disease Burden on Clinical Outcomes of Female Acute Myocardial Infarction Patients.

Owing to the paucity of information on the clinical outcomes in female patients with acute myocardial infarction (AMI) in relation to the comorbid disease burden, we explored the differences in their clinical outcomes and identified predictive indicators. A total of 3,419 female AMI patients were stratified into two groups: Group A (those with zero or one comorbid diseases) (n=1,983) and Group B (those with two to five comorbid diseases) (n=1,436). Five comorbid conditions were considered: hypertension, diabetes mellitus, dyslipidemia, prior coronary artery disease, and prior cerebrovascular accidents. The primary outcome was major adverse cardiac and cerebrovascular events (MACCEs). The incidence of MACCEs was higher in Group B than in Group A in both the unadjusted and propensity score-matched data. Among the comorbid conditions, hypertension, diabetes mellitus, and prior coronary artery disease were found to be independently associated with an increased incidence of MACCEs. Higher comorbid disease burden was positively associated with adverse outcomes in the female population with AMI. Since both hypertension and diabetes mellitus are modifiable and independent predictors of adverse outcomes after AMI, it may be necessary to focus on the optimal management of blood pressure and glucose levels to improve cardiovascular outcomes.

1830. Epidemiology of Recurrent Bacterial Bloodstream Infections in the US Military Health System

Abstract Background The epidemiology of recurrent bacterial bloodstream infections (rBSI) has not been fully characterized. Evaluating rBSI represents opportunities to inform morbidity risk factors and prevention strategies. We describe the clinical and microbiological features of rBSI in the US Military Health System (MHS) in a prospective cohort study, including retired and active-duty US uniformed service members and their beneficiaries. Methods We collected data for rBSI episodes from MHS beneficiaries (Jan 2010 – Dec 2019). A rBSI is defined as growth of the same bacterial pathogen in blood culture &amp;gt;14 days after the index or previous episode. Demographics and comorbidities were collected prior to the index BSI. Microbiological data were obtained from the Navy and Marine Corps Public Health Center. Descriptive statistics are presented. Results A total of 12,749 beneficiaries were diagnosed with a BSI attributed to 1 of the 15 most common bacterial pathogens associated with BSI in the MHS, with 646 (5.1%) experiencing a rBSI. Escherichia coli had the largest proportion among all patients with rBSI (31% of 646); however, Enterococcus spp. accounted for the highest proportion of rBSI within a given pathogen subgroup (7.4% of 1,154 Enterococcus BSI; Table). Pseudomonas aeruginosa BSI had the shortest average time to recurrence (119 days), and Acinetobacter spp. had the highest frequency of BSI recurrences per patient (mean of 3). Male sex (59.9%) and age ≥65 years (52.9%) were most common among the rBSI patients. The updated Charlson Comorbidity index score preceding the index BSI was a median of 5.0, and chronic pulmonary disease (57.3%) and diabetes (56.6%) contributed the largest proportion of common comorbidities. A total of 88 (13%) rBSI patients had their index BSI while hospitalized following trauma where S. aureus was the most common (37.5%) bacterial pathogen. Conclusion Overall, the proportion of rBSI (5.1%) in our cohort of MHS beneficiaries was generally lower than that previously reported in the literature. Individuals with rBSI had a substantial burden of comorbid disease with 13% having trauma precede the index BSI. Identifying risk factors for recurrence may improve management strategies of primary BSI and may reduce morbidity of subsequent BSI. Disclosures John H. Powers, III, MD, Arrevus: Advisor/Consultant|Eicos: Advisor/Consultant|Evofem: Advisor/Consultant|Eyecheck: Advisor/Consultant|Gilead: Advisor/Consultant|GlaxoSmithKline: Advisor/Consultant|OPKO: Advisor/Consultant|Resolve: Advisor/Consultant|Romark: Advisor/Consultant|SpineBioPharma: Advisor/Consultant|UTIlity: Advisor/Consultant|Vir: Advisor/Consultant.

The Impact of Drug Interactions on Outcomes in Ibrutinib-Treated Patients with Chronic Lymphocytic Leukemia in Routine Clinical Care: A Population-Based Cohort Study

Introduction: Ibrutinib is extensively metabolized by cytochrome P450 CYP3A and drug interactions pose a considerable challenge with its use in B-cell malignancies. Patients with chronic lymphocytic leukemia (CLL) are often older with multiple comorbidities and complex medication histories. In this study, we aimed to evaluate the impact of drug interactions, in particular CYP3A inducers and inhibitors, on survival in patients with CLL treated with ibrutinib in routine clinical care. Methods: We conducted a population-based cohort study using linked administrative healthcare databases from Ontario, Canada. All Ontario residents aged ≥66 years with CLL started on ibrutinib between January 2007 and March 2019 were identified and followed from the date of first ibrutinib prescription (index date) until March 1, 2020. The observation window was terminated in the event of death, no ibrutinib prescription for 120 days, or at the time of allogenic stem cell transplant, whichever occurred first. Cumulative medication exposure (30-day increments) to concomitant CYP3A inducers and/or CYP3A inhibitors were examined from 90 days prior to index date to the end of the observation window as a time-varying covariate. A comprehensive list of CYP3A inducers and inhibitors were obtained from the FDA (2020) and Flockhart Table of Cytochrome P450 Drug Interactions (Flockhart et al., 2021). The primary outcome was overall survival (OS). Cox regression, controlling for comorbid disease burden (aggregated diagnosis groups; ADG), ibrutinib dose (full vs. reduced) and sociodemographic factors (age, sex) examined the relationship between medication exposure and OS. Results: We identified 642 patients with CLL treated with ibrutinib in Ontario between January 1, 2007 and March 1, 2019. The median age was 74 years (interquartile range (IQR), 69 - 80), 34.4% were female with a median weighted ADG score of 17 (IQR, 8 - 25), indicating a high burden of comorbidities in our cohort. At baseline, 563 (87.7%) patients received full-dose ibrutinib and 372 patients (57.9%) were on ibrutinib as first-line therapy. The median follow-up time from ibrutinib initiation was 2 years (IQR, 1.3 - 3.0) with 162 deaths (25.2%) and the median OS was not reached. During the study period, 131 patients (20.4%) received a concomitant CYP3A inducer, and 179 patients (27.9%) received a concomitant CYP3A inhibitor. On univariate analysis, we identified an association of increased risk of all-cause death with increased age (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.04 - 1.08, p <0.0001), exposure to a concomitant CYP3A inducer (HR 1.04, 95% CI 1.01 - 1.07, p = 0.009), and greater comorbid disease burden (HR 1.02, 95% CI 1.00 - 1.03, p = 0.01). Exposure to concomitant CYP3A inhibitors was not significantly associated with all-cause death (HR 1.00, 95% CI 0.98 - 1.02, p = 0.84). Multivariable analysis adjusting for age, sex, comorbid disease burden and ibrutinib dose (full vs. reduced) demonstrated an increased risk of death for patients on a concomitant CYP3A inducer (HR 1.04 for each 30-day increase in exposure, 95% CI 1.01 - 1.07, P = 0.016; see table) whereas CYP3A inhibitors had no significant effect on all-cause death (HR 0.99, 95% CI 0.97 - 1.01, P = 0.43). The most common cause of death for patients on a concomitant CYP3A inducer, where known, was CLL (54.9%). Conclusions: Despite known drug interactions, CLL patients on ibrutinib and concomitant CYP3A inducers/inhibitors is common in routine clinical care. We demonstrate an association between CYP3A inducer exposure and an increased risk of death, which may be in part due to decreased ibrutinib levels. Our study highlights the importance of pharmacovigilance. Further analyses are underway to better understand the impact of drug interactions on ibrutinib treatment complications Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Anterior approach lumbar fusions cause a marked increase in thromboembolic events: Causal inferences from a propensity-matched analysis of 1147 patients

ObjectiveAnterior lumbar fusions are thought to be associated with elevated venous thromboembolic event (VTE) rates, but the magnitude of this increase in VTE is not well described. The objective of this study was to quantify any increase in VTE caused by anterior approach lumbar fusion. Methods1147 consecutive lumbar fusions performed at our institution over a six-year period were identified, and clinical and demographic data were collected. K-nearest neighbor propensity score matching and propensity score adjusted regression were performed. Patients undergoing anterior versus posterior approach lumbar fusions were matched according to age, body mass index, sex, VTE history, estimated blood loss, length of surgery, transfusion, selection for postoperative intensive care unit (ICU) admission, comorbid disease burden, and use of chemoprophylactic anticoagulation. ResultsAnterior approach surgery (OR=4.29, p < 0.001), a history of VTE (OR=8.67, p < 0.001), age (OR=1.53, p = 0.014), length of surgery (OR=1.16, p = 0.044), and selection for postoperative ICU admission (OR=4.60, p = 0.005) were independently associated with VTE on multivariable regression. 1058 anterior or posterior approach fusion patients were matched. After matching, overall bias was reduced by 71.0 %, no covariates remained significantly different between groups, and propensity scores were well balanced between populations (Rubin’s B≤0.25, 0.5 ≤Rubin’s R≤2.0). Significantly more patients in the anterior group underwent lower extremity duplex ultrasonography (LED) (36.9 % vs. 14.8 %, OR=3.36 [2.38, 4.76], p < 0.0001), and a statistically insignificantly higher proportion of LEDs were positive among patients in the anterior group (23.2 % vs. 13.2 %, OR=1.99 [0.92, 4.25], p = 0.108). After matching, the rate of VTE was 8.6 % for the anterior group and 1.3 % for the posterior group, with anterior approach surgery causing an increase in VTE by 7.2 % (95 % CI [2.28 %, 12.16 %], p = 0.004). ConclusionAmong patients undergoing lumbar fusions, anterior approach surgery causes an increase in VTE by 7.2%, which is a multifold increase in the proportion of patients with thromboembolic complications.

Commentary: Surgical Site Infection in the Intensive Care Setting After Posterior Spinal Fusion: A Case Series Highlighting the Microbial Profile, Risk Factors, and the Importance of Comorbid Disease Burden.

Commentary: Surgical Site Infection in the Intensive Care Setting After Posterior Spinal Fusion: A Case Series Highlighting the Microbial Profile, Risk Factors, and the Importance of Comorbid Disease Burden.

Concomitant cervical spine fractures are the primary driver of disability after traumatic vertebral artery dissection: A Case series of 123 patients.

Traumatic vertebral artery dissections (tVADs) occur in up to 20% of patients with head trauma, yet data on their presentation and associated sequelae are limited. To characterize the tVAD population and identify factors associated with clinical outcomes. We retrospectively analyzed all cases of tVAD at our institution from January 2004 to December 2018 with respect to mechanism of injury, clinical presentation, anatomic factors, associated pathologies, and relevant outcomes. Of the 123 patients with tVAD, the most common presenting symptoms were neck pain (n=76, 67.3%), headache (57.5%), and visual changes (29.6%). 101 cases (82.1%) were unilateral, and 22 cases (17.9%) were bilateral. V2 was the most involved anatomic segment (83 cases, 70.3). 30 cases (25.4%) led to stroke, and 39 cases (31.7%) had a concomitant cervical fracture. The anatomic segment and number of segments involved, and baseline clinical and demographic characteristics were not associated with risk of stroke. Patients with associated fractures were older (50.3 years v. 36.4 years, p=0.0233), had a higher comorbid disease burden (CCI 1 vs. CCI 1, p<0.0007), were more likely to smoke (OR 3.0 [1.2178, 7.4028], p=0.0202), be male (OR 7.125 [3.0181, 16.8236], p<0.0001), and have mRS≥3 at discharge (OR 3.0545 [1.0937, 8.5752], p=0.0449). On multivariable regression, only fracture independently predicted mRS≥3 at discharge (OR 5.6898 [1.5067, 21.4876], p=0.010). tVADs may be associated with stroke and/or cervical fracture. Presenting symptoms predict stroke, but baseline demographic and clinical characteristics do not. Comorbid cervical fractures, not stroke, drive negative outcomes.

Stroke and intracardiac thrombus: A case series

IntroductionCardioembolism may cause 20%–40% of all ischemic strokes. Up to 22% of cardioembolic strokes are associated with intracardiac thrombi and occur in patients with a high burden of comorbid cardiac disease. Aim and methodsTo describe the in-hospital experience of stroke patients with intracardiac thrombi. A retrospective 1 center study was carried out. Demographic, clinical, stroke, echocardiographic, and outcome data of stroke patients with intracardiac thrombi were extracted. ResultsFrom 2018 to 2019, 530 stroke patients were admitted. Nine (1.7%) had intracardiac thrombi, 100% males with mean age 63.3 years. There were a high prevalence of cardiovascular risk factors, with anterior circulation stroke in 8 (88%) and large vessel occlusion in 8 (88%). Most had major echocardiographic findings and 8 (88%) had a discharge outcome Rankin scale score > 3. ConclusionIntracardiac thrombus is not an uncommon cause of stroke. Cardiac ultrasound is a sensitive diagnostic method and should be sought in older patients with high prevalence of cardiovascular risk factors and history of cardiac disease.

32240 Baseline characteristics and comorbid conditions in patients with moderate-to-severe plaque psoriasis enrolled in the Psoriasis Study of Health Outcomes (PSoHO)

Aim: This interim analysis of the Psoriasis Study of Health Outcomes (PSoHO) describes the baseline comorbidities of the first 700 enrolled patients to improve our understanding of treatment patterns in the real-world setting. Methods: PSoHO is a 3-year international, prospective, multicenter, noninterventional cohort study comparing the clinical effectiveness of antiinterleukin (IL)-17A biologics versus other biologics in treating PsO. Patients (≥18 years) had moderate-to-severe PsO and initiated/switched biologics during routine medical care. Physicians recorded patients’ baseline comorbidities from a prespecified list. Baseline comorbidity rates by treatment group were analyzed using Fisher exact test. Results: This interim cohort (n = 700) was 57.7% male, with a mean baseline (standard deviation) age of 46.2 (13.7) years, Body Mass Index of 29.5 (6.9), Psoriasis Area and Severity Index of 14.8 (8.6) and Dermatology Life Quality Index of 11.9 (7.5). The mean number of comorbidities was 1.3 (1.8) with 59.2% (181/306) of the anti-IL-17A cohort and 59.4% (234/394) of the other biologics cohort reporting comorbidities. For the anti-IL-17A and other biologics cohorts, the most frequent comorbidities were psoriatic arthritis (25.2% [77/306] and 19.5% [77/394]), hypertension (25.5% [78/306] and 25.1% [99/394]), dyslipidemia (19.3% [59/306] and 17.0% [67/394]) and diabetes (8.8% [27/306] and 10.7% [42/394]), respectively. No significant differences were observed between cohorts for all reported comorbidities. Conclusion: This interim analysis suggests that biologic-treated patients with PsO have more heterogenous disease and a higher comorbid disease burden in the real world than clinical trial populations, including conditions that usually exclude clinical trial enrollment.

Retrospective assessment of the association between co-morbid disease burden and biochemical parameters in hospitalized hypertensive COVID-19 patients

Background/Aim: Hypertension (HT) was examined as a risk factor affecting the progression of the 2019 novel coronavirus disease (COVID-19). In COVID-19 patients, it can be found in many co-morbid diseases, along with hypertension. It is not clear whether the co-morbid burden of the disease affects the prognosis in hypertensive COVID-19 patients and which biochemical parameters may be indicative of this. Therefore, this study was designed to determine the effect of co-morbid disease burden on biochemical parameters in hospitalized hypertensive COVID-19 patients.&#x0D; Methods: After receiving approval from the University Ethics Committee, demographic, clinical, radiological, and laboratory data of 250 hospitalized hypertensive COVID-19 patients between May 2020 and Sept 2020 were screened. Patients with missing records and unclear history of hypertension drug use were excluded from the study. A total of 215 patients were included in the study. Patients were divided into four groups according to the co-morbidity status: (1) HT alone (Group HT0), (2) HT+ Diabetes Mellitus (DM) (Group HTDM1), (3) HT+one co-morbidity exclude DM (Group HT2), and (4) HT+at least two co-morbidities (Group HT3).&#x0D; Results: We analyzed the data of 105 female and 110 male patients. Of the 215 patients whose data were evaluated in this study, 15 patients died. Two hundred people were discharged with recovery. The mortality rate was 7%. Of the hypertension patients, 34.9% had DM, 32.6% had coronary artery disease (CAD), 30.2% had chronic obstructive pulmonary disease (COPD), 16.3% had heart failure (HF), 23.3% had chronic kidney failure (CKD), and 9.3% had cerebrovascular disease (CVD). Twenty-five percent were smokers. Urea, creatinine, direct bilirubin (DBil), and Troponin-I values were significantly higher in the Group HT3 compared to the Group HT0, Group HTDM1, and Group HT2 (P &lt; 0.001, P &lt; 0.001, P &lt; 0.001, P = 0.002 respectively). Glomerular filtration rate (GFR) and albümin levels were significantly lower in Group HT3 than in Group HT0, Group HTDM1, and Group HT2 (P &lt; 0.001 and P &lt; 0.001, respectively). The logistic regression model was statistically significant (χ2(7) = 69.088 and P &lt; 0.001); advanced age, decrease in GFR and plateletcrit (PCT) levels, and increase in D-dimer and DBil levels were observed as predictive parameters of mortality in all hospitalized COVID-19 HT patients.&#x0D; Conclusion: We determined that SARS-CoV-2 pneumonia patients with HT plus at least two co-morbidities were more serious than other patient groups in terms of organ damage and biochemical variables. In our study, we observed an increase in urea, creatinine, D-dimer, Dbil, and Troponin-I values and a decrease in GFR and albumin values as the co-morbidity burden increased in hypertensive COVID-19 patients. However, a decrease in GFR and hemogram PCT levels and an increase in D-dimer and DBil levels could be risk factors for mortality.

Frailty predicts readmission, reoperation, and infection after posterior spinal fusion: An institutional series of 3965 patients

ObjectiveFrailty is a measure of physiologic vulnerability conceptualized as the accumulation of deficits with aging, and may be useful for predicting risk of adverse events following posterior spinal fusion. Our objective was to investigate the utility of the Canadian Study on Health and Aging (CHSA) Modified Frailty Index (mFI) in patients undergoing posterior spinal fusion (PSF) as a predictor of several surgical quality metrics including readmission, reoperation, and surgical site infection. MethodsWe examined 3965 consecutive PSF patients treated at our institution between 2000 and 2015, and collected demographic, clinical, and frailty and comorbid disease burden measures using the mFI and Charlson Comorbidity Index (CCI). We examined trends and changes in these clinical and demographic characteristics over the course of the study period. We performed multivariable regression to identify independent predictors of readmission, reoperation, and surgical site infection. ResultsOver the course of the study period, the mean patient age increased linearly year-over-year (ß=0.60 [0.48, 0.72], p < 0.0001, R=0.94), while the SSI rate decreased linearly (ß=−0.14 [−0.27, −0.02], p = 0.0249, R=0.56), and frailty scores did not change significantly (p = 0.8124, R=0.065). Among all patients undergoing PSF, postoperative wound infection was independently associated with number of levels fused (OR=1.104 p < 0.001), frailty as measured by mFI (OR=1.150 p = 0.006), and BMI (OR=1.041 p = 0.008). Frailty was also independently associated with postoperative ICU admission (OR=1.1080 p = 0.005), 30-day readmission (OR=1.181 p < 0.001), and 30-day reoperation (OR=1.128 p < 0.001). Among all patients, rate of postoperative wound infection increased with increasing frailty (p = 0.0002) and increasing comorbid disease burden (chi-square p = 0.0012). ConclusionThe mFI predicts adverse events among patients undergoing PSF, including readmission, reoperation, and surgical site infection. When controlling for frailty, age was not an independent predictor of adverse events.