Chest Radiographic Findings in High-risk Covid-19 Pneumonia Patients

Background/ objectivesThe severity of Covid-19 pneumonia has shown a positive association with co-existing risk factors. However, the exact nature of lung involvement in high-risk Covid-19 patients is yet to be resolved. Therefore, we evaluated the CXR features, temporal progression, and the factors associated with CXR severity in high-risk patients.MethodsChest X-rays (n=289) of Covid-19 infected high-risk adults (n=228) treated at the Base Hospital Homagama were evaluated to record CXR features, their temporal progression, CXR severity score and the patient outcomes. ResultsThe studies patients (48.2% men) were in mean age(SD) of 59(15) years. The most frequent CXR features were patchy ground-glass opacities (49%; GG) and patchy consolidations (42%; CON). They showed bilateral (100%) involvement, superoinferior gradient (100%) and diffuse (27%), peripheral (18%) or perihilar (10%) distribution. CON was the predominant opacity among the non-survivors and GG among the survivors (χ2=14.73; p=0.001). Right lung predominant (28%) asymmetrical lung involvement was more frequent than bilateral symmetrical (16%) or left lung predominance (7%). Progression into fatal disease was significantly higher when the lung involvement is asymmetrical: right predominance: ODDs:0.502; p=0.023; left predominance: ODDs:0.268; p=0.002. The CXRs were frequently normal in early (66%) and progressive (56%; χ2=36.64; p<0.001) stages than in peak or resolving stages. The predictors of CXR severity included age (β:0.140; 95% CI:0.041–0.233; p=0.004), male gender (β:4.140; 95% CI:1.452–6.481; p=0.003), and disease day (β:0.622; 95% CI:0.301–0.942; p<0.001). ConclusionThis study decoded the CXR features of Covid-19 pneumonia in a high-risk cohort while describing their associations.

Adjusting growth standards for fetal sex improves correlation of small babies with stillbirth and adverse perinatal outcomes: A state-wide population study

Objective: Identify the proportion of infants reclassified if sex-specific birthweight charts were used, and if this reclassification has an impact on the correlation between birthweight centile and adverse perinatal outcome. Design: Retrospective cohort study Setting: Victoria, Australia. Population: All infants born from 2005-2015 (529,261) Methods: We applied GROW centiles, either adjusted or unadjusted for fetal sex. We compared proportions of small for gestational age (SGA, <10th centile) infants, then the populations of males considered small only by sex-specific charts and females considered small only by unadjusted charts. Main Outcome Measures: Stillbirth, combined perinatal mortality, NICU admissions, Apgars <7 at 5 minutes, emergency caesarean sections. Results: Of those <10th centile by unadjusted charts, 39.6% were male, and 60.5% female. Using sex-specific charts, 50.3% <10th centile were male and 49.7% female. 9,449 (19.2%) females that were SGA according to unadjusted charts were appropriate for gestational age (AGA,>10th-<90th centile) using sex-specific charts. These reclassified newborn females were not at increased risk of adverse outcomes compared with an AGA infant, but were at increased risk of being iatrogenically delivered for suspected growth restriction (RR 4.90, 95%CI 4.39–5.48). 8,048 male infants were reclassified as SGA by sex-specific charts (25% SGA increase). Compared with AGA infants, these reclassified male newborns were at greater risk of stillbirth (RR 1.94, 95%CI 1.30-2.90) and all other adverse perinatal outcomes. Conclusions: Sex-specific growth standards classify a new high-risk cohort of male infants as SGA, and exclude a cohort of females, whose risk is no greater than appropriately grown infants.

Adverse clinical outcomes in people at clinical high-risk for psychosis related to altered interactions between hippocampal activity and glutamatergic function

Preclinical rodent models suggest that psychosis involves alterations in the activity and glutamatergic function in the hippocampus, driving dopamine activity through projections to the striatum. The extent to which this model applies to the onset of psychosis in clinical subjects is unclear. We assessed whether interactions between hippocampal glutamatergic function and activity/striatal connectivity are associated with adverse clinical outcomes in people at clinical high-risk (CHR) for psychosis. We measured functional Magnetic Resonance Imaging of hippocampal activation/connectivity, and 1H-Magnetic Resonance Spectroscopy of hippocampal glutamatergic metabolites in 75 CHR participants and 31 healthy volunteers. At follow-up, 12 CHR participants had transitioned to psychosis and 63 had not. Within the clinical high-risk cohort, at follow-up, 35 and 17 participants had a poor or a good functional outcome, respectively. The onset of psychosis (ppeakFWE = 0.003, t = 4.4, z = 4.19) and a poor functional outcome (ppeakFWE < 0.001, t = 5.52, z = 4.81 and ppeakFWE < 0.001, t = 5.25, z = 4.62) were associated with a negative correlation between the hippocampal activation and hippocampal Glx concentration at baseline. In addition, there was a negative association between hippocampal Glx concentration and hippocampo-striatal connectivity (ppeakFWE = 0.016, t = 3.73, z = 3.39, ppeakFWE = 0.014, t = 3.78, z = 3.42, ppeakFWE = 0.011, t = 4.45, z = 3.91, ppeakFWE = 0.003, t = 4.92, z = 4.23) in the total CHR sample, not seen in healthy volunteers. As predicted by preclinical models, adverse clinical outcomes in people at risk for psychosis are associated with altered interactions between hippocampal activity and glutamatergic function.

Obesity and accelerated epigenetic aging in a high-risk cohort of children

Background: New insights into mechanisms linking obesity to poor health outcomes suggest a role for cellular aging pathways, casting obesity as a disease of accelerated biological aging. Although obesity has been linked to accelerated epigenetic aging in middle-aged adults, the impact during childhood remains unclear. We tested the association between body mass index (BMI) and accelerated epigenetic aging in a cohort of high-risk children. Participants were children (N=273, aged 8 to 14 years, 82% investigated for maltreatment) recruited to the Child Health Study, an ongoing prospective study of youth investigated for maltreatment and a comparison youth. BMI was measured as a continuous variable. Accelerated epigenetic aging of blood leukocytes was defined as the age-adjusted residuals of several established epigenetic aging clocks (Horvath, Hannum, GrimAge, PhenoAge) along with a newer algorithm, the DunedinPoAm, developed to quantify the pace-of-aging. Hypotheses were tested with generalized linear models. Results: Higher BMI was significantly correlated with older chronological age, maltreatment status, household income, blood cell counts, and three of the accelerated epigenetic aging measures: GrimAge (r=0.29, P<.0001), PhenoAge (r=0.25, P<.0001), and DunedinPoAm (r=0.37, P<.0001). In fully adjusted models, GrimAge (b=.06; P=.007) and DunedinPoAm (b=.0017; P<.0001) remained significantly associated with higher BMI. Maltreatment-status was not independently associated with accelerated epigenetic aging after accounting for other factors. Conclusion: In a high-risk cohort of children, higher BMI predicted epigenetic aging as assessed by two epigenetic aging clocks. These results suggest the association between obesity and accelerated epigenetic aging begins in early life, with implications for future morbidity and mortality risk.

Mid-Term Outcomes of Veno-Venous Extracorporeal Membrane Oxygenation as a Bridge to Lung Transplantation: Comparison with Non-Bridged Recipients

Objectives: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is increasingly being used in acutely deteriorating patients with end-stage lung disease as a bridge to transplantation (BTT). It can allow critically ill recipients to remain eligible for lung transplant (LTx) while reducing pretransplant deconditioning. We analyzed early and mid-term postoperative outcomes of patients on VV-ECMO as a BTT and the impact of preoperative VV-ECMO on posttransplant survival outcomes. Methods: All consecutive LTx performed at our institution between January 2012 and December 2018 were analyzed. After matching, BTT patients were compared with non-bridged LTx recipients. Results: Out of 297 transplanted patients, 21 (7.1%) were placed on VV-ECMO as a BTT. After matching, we observed a similar 30-day mortality between BTT and non-BTT patients (4.6% vs. 6.6%, p=0.083) despite a higher incidence of early postoperative complications (need for ECMO, delayed chest closure, acute kidney injury). Furthermore, preoperative VV-ECMO did not appear associated with 30-day or 1-year mortality in both frequentist and Bayesian analysis (OR 0.35, 95%CI 0.03-3.49, p=0.369; OR 0.27, 95%CrI 0.01-3.82, P=84.7%, respectively). In sensitivity analysis, both subgroups were similar in respect to 30-day (7.8% vs. 6.5%, p=0.048) and 1-year mortality (12.5% vs. 18%, p=0.154). Conclusions: Patients with acute refractory respiratory failure while waiting for LTx represent a high-risk cohort of patients. We observed that these patients can be successfully bridged to LTx with VV-ECMO with post-transplant mortality comparable to non-BTT patients.

1429. Real-World Study of Patients with Uncomplicated Urinary Tract Infection in the United States: High-Risk Comorbid Conditions and Burden of Illness

Background Urinary tract infections (UTIs) are associated with significant morbidity and economic burden, particularly in the elderly and patients with comorbidities. We used real-world data (RWD) to assess healthcare resource use (HRU) and costs in patients with uncomplicated UTI (uUTI) and high-risk comorbid conditions in the US. Methods This was a retrospective cohort study (IBM MarketScan RWD, commercial/Medicare Supplemental claims January 1, 2014–December 31, 2017) of females ≥ 12 years of age with uUTI who had an oral antibiotic prescription ± 5 days of uUTI diagnosis (index date) and continuous health-plan enrollment for ≥ 1 year pre-/post index date. Five high-risk cohorts and matched-control cohorts (baseline age, region) were identified: controlled type 2 diabetes (T2D), mild/moderate chronic kidney disease (CKD), recurrent UTI (rUTI), elderly (ELD), and postmenopausal (PMP) (Table 1). Sample sizes were balanced via random match selection (1:5 case:control). uUTI-related HRU and costs were compared between cases and controls (index episode/1-year follow-up) using multivariable generalized linear models. Table 1. Cohort assignment for high-risk cohorts and controls Results Of 339,100 patients with uUTI, case/control cohorts comprised T2D, n=15,423/n=77,115; CKD, n=1041/n=5205; rUTI, n=7937/n=39,685; ELD, n=23,666/n=118,330; and PMP, n=105,608/n=211,216 patients. HRU trends across cohorts varied. During 1-year followup, outpatient visits were significantly different for cases versus controls in the T2D, rUTI, and PMP cohorts (p ≤ 0.0079), with higher case than control values in the rUTI and PMP cohorts; pharmacy claims were significantly higher for rUTI, ELD, and PMP cases, and inpatient visits were significantly higher for ELD and PMP cases, versus controls (all p &lt; 0.0001; Table 2). Adjusted total uUTI-related costs (emergency room + outpatient + pharmacy) were significantly different (p &lt; 0.0001) for cases versus controls at index episode and during follow-up in all cohorts except CKD: case values were higher than controls at index episode and during follow-up in the T2D cohort, and during follow-up in the rUTI and ELD cohorts (Table 3). Table 2. uUTI-related HRU* for cases versus controls according to high-risk cohort Table 3. uUTI-related costs* for cases versus controls according to high-risk cohort Conclusion Females in some high-risk case cohorts had higher uUTI-related HRU and costs versus controls. Further studies of relationships between comorbidities and uUTI burden are needed. Disclosures Madison T. Preib, MPH, STATinMED Research (Employee, Former employee of STATinMED Research, which received funding from GlaxoSmithKline plc. to conduct this study) Alen Marijam, MSc, GlaxoSmithKline plc. (Employee, Shareholder) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder) Daniel C. Gibbons, PhD, GlaxoSmithKline plc. (Employee, Shareholder) Xiaoxi Sun, MA, STATinMED Research (Employee, Employee of STATinMED Research, which received funding from GlaxoSmithKline plc. to conduct this study) Christopher Adams, MPH, STATinMED Research (Employee, Employee of STATinMED Research, which received funding from GlaxoSmithKline plc. to conduct this study) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder)

1422. Real-World Study of the Effects of Inappropriate or Suboptimal Treatment on the Burden of Illness Among Patients with Uncomplicated Urinary Tract Infection and High-Risk Comorbid Conditions in the United States

Background Urinary tract infections (UTIs) are associated with significant morbidity and economic burden. Nitrofurantoin (NFT) and fosfomycin are among the first-line treatments for uncomplicated UTI (uUTI) recommended by Infectious Diseases Society of America (IDSA) 2011 guidance. We used real-world data (RWD) to assess patterns of appropriate and optimal (AP&OP) and inappropriate or suboptimal (IA/SO) antibiotic (AB) prescribing (RX), and related healthcare resource use (HRU) and costs, in US uUTI patients with high-risk comorbid conditions. Methods This was a retrospective cohort study of RWD (IBM MarketScan, commercial/Medicare Supplemental claims January 1, 2014–December 31, 2017) in females ≥ 12 years of age with uUTI, who had an oral AB prescription ± 5 days of uUTI diagnosis (index date) and continuous health-plan enrollment ≥ 1 year pre-/post-index date. Patients were stratified into high-risk cohorts (Table 1) and by AB RX (AP&OP and IA/SO) during first uUTI episode (within 28 days of index). AP&OP RX followed IDSA guidance, IA RX did not; SO RX was considered a proxy for treatment failure (e.g., AB switch or a second UTI diagnosis [acute care setting] in index episode). Sample size was balanced via random match selection, AP&OP:IA/SO ratio 1:5 (age and region). uUTIrelated HRU and costs were compared between cohorts (at index episode and 1-year follow-up) via multivariable analysis. Table 1. High-risk cohorts identified in the study Results IA/SO AB RX was highest in the elderly cohort (94.3%, likely influenced by renal impairment/no NFT RX in this group) and &gt; 90% in other cohorts; AP&OP AB RX was highest in the postmenopausal cohort (9.0%). IA/SO AB RX in all cohorts was associated with significantly higher uUTI-related HRU (outpatient visits and pharmacy claims) per index episode/during follow-up versus AP&OP AB RX (p ≤ 0.0237, Table 2). IA/SO AB RX in all cohorts was associated with significantly higher adjusted total costs per index episode/during follow-up versus AP&OP AB RX (p &lt; 0.05; Table 3). Table 2. uUTI-related HRU* per patient according to high-risk cohort and stratified by AB RX Table 3. uUTI-related costs* per patient according to high-risk cohort and stratified by AB RX Conclusion Over 90% of females in each high-risk cohort identified had IA/SO AB RX (outside IDSA 2011 guidance for uUTI treatment), leading to high HRU and cost burden. This suggests an unmet need for uUTI symptom relief, new treatments, training, and improved RX practices in the US and, furthermore, a need for additional research in this area. Disclosures Madison T. Preib, MPH, STATinMED Research (Employee, Former employee of STATinMED Research, which received funding from GlaxoSmithKline plc. to conduct this study) Alen Marijam, MSc, GlaxoSmithKline plc. (Employee, Shareholder) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder) Daniel C. Gibbons, PhD, GlaxoSmithKline plc. (Employee, Shareholder) Xiaoxi Sun, MA, STATinMED Research (Employee, Employee of STATinMED Research, which received funding from GlaxoSmithKline plc. to conduct this study) Christopher Adams, MPH, STATinMED Research (Employee, Employee of STATinMED Research, which received funding from GlaxoSmithKline plc. to conduct this study) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder)