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Background and Aims : EUS-guided needle-based confocal laser endomicroscopy (nCLE) improves the diagnostic accuracy of pancreatic cystic lesions (PCLs) but concerns regarding its expense have limited widespread adoption of this technology. We conducted a cost-benefit analysis to assess the healthcare resource implications of adding EUS-nCLE to the standard of care (SOC) management of PCLs. Methods : A post-hoc analysis of a prospective study (2015-2018) evaluating EUS-nCLE for the diagnosis of PCLs was performed. The SOC diagnosis was based on clinical history, PCL morphology, and cyst fluid analysis. A minimum of 5-years of surveillance was included, the cost of EUS and MRI/MRCP was derived from institutional billing data (US$), and the total hospital costs (adjusted for inflation) for pancreatic operations were derived from the National (US) Readmission Database. Results : A reference diagnosis was available in 93 subjects (mean cyst size=36.4±15.7 mm; surgical histopathology, n=67 and diagnostic molecular markers in cyst fluid, n=26). SOC and nCLE were discordant in 13 (14%) subjects. The addition of nCLE led to 11 subjects being clinically downstaged from mucinous to non-mucinous not warranting surgery (total cost savings= $1,080,418), 1 subject upstaged from non-mucinous to mucinous, warranting surgical resection (cost savings of 5-years surveillance: $46,200), and 1 subject incorrectly classified as non-mucinous (cost excess of 5-years surveillance: $46,200). Overall, the addition of nCLE led to a net savings of $ 442,438 (mean: $ 4,757.40 /patient) for this cohort. Conclusions : EUS-nCLE is potentially cost-beneficial in the management of PCLs (≥ 3 cm) by preventing at least one unnecessary pancreatic surgery for every ten subjects undergoing evaluation by current practices. ClinicalTrials.gov number: NCT02516488.

Background Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma. Recent advances in immunotherapy have resulted in the development of chimeric antigen receptor–modified T-cell (CAR-T) therapy, such as axicabtagene ciloleucel (axi-cel). However, axi-cel administration is not without risks of toxicity. Patients and Methods This retrospective study of 37 patients with relapsed or refractory diffuse large B-cell lymphoma evaluated the incidence and severity of common and severe safety events after axi-cel treatment in a real-world setting. Ninety percent of patients had received 3 or more prior lines of therapy (median prior therapies 3, range 2-7) before receiving CAR-T therapy, and 32.4% had relapsed after prior stem-cell transplantation. Results All but one patient experienced cytokine release syndrome (CRS) of any grade (97.3%). Of those 36 patients, 83.3% experienced maximum CRS grade of 1 or 2, occurring after a median of 27 hours and persisting for a median of 6 days. Twenty-seven patients (73.0%) experienced neurotoxicity of any grade. Of those 27 patients, 96.3% experienced maximum neurotoxicity grade of 2 or higher, occurring after a median of 145 hours (6 days) and persisting for a median of 7 days. All 10 patients aged 65 or older had neurotoxicity of grade 2 or higher, compared to 59.3% (11/27) under age 65 (P = .02). Patients with baseline Eastern Cooperative Oncology Group performance status score of 2 were significantly more likely to have shorter time to neurotoxicity compared to patients with performance status of 0 (P = .01). Conclusion With more real-life experience and data, we will be able to define and refine management of toxicities unique to CAR-T therapy.

Background EUS-guided needle-based confocal laser endomicroscopy (nCLE) has not been widely adopted for the differentiation of pancreatic cystic lesions (PCLs), perhaps due to a perceived difficulty in learning novel CLE image patterns. Hence, we sought to investigate the optimal teaching modality for interpretation of nCLE imaging from PCLs. Methods Sixteen nCLE-naive observers blinded to clinical data were randomized into didactic (classroom-based) versus self-directed (computer-based) teaching groups to review nCLE videos and differentiate mucinous and non-mucinous PCLs. The study was conducted concurrently for both groups in 3 phases. Phase-1-Teaching: both groups received an overview of EUS-nCLE of PCLs. Phase-2-Training: assessment of 20 EUS-nCLE subject-videos; the didactic group had a feedback session with an nCLE expert while the self-directed group received this information via pre-recorded presentation. Phase-3-Testing: assessment of 50 EUS-nCLE subject-videos. Results For all observers (n = 16), the diagnostic accuracy for nCLE-based differentiation of mucinous from non-mucinous PCLs was higher (p=0.005) in the Phase-3-Testing (94.6%, 95%CI: 92-96%) than in Phase-2-Training (89.9%, 95%CI: 85-93%). During Phase-3-Testing, both the didactic and self-directed teaching groups achieved a comparable (p=0.48) diagnostic accuracy of 93.9% and 95.4%, respectively. The interobserver agreement (kappa, standard error) for the differentiation of mucinous from non-mucinous PCLs improved from Phase-2-Training to Phase-3-Testing stage, and was “substantial” for both the didactic (k=0.81, 0.03) and self-directed (k=0.79, 0.03) training groups. Conclusion Notwithstanding didactic and self-directed teaching, a ‘training’ and ‘test’ strategy accomplished high diagnostic accuracies and considerable interobserver agreement among naive observers for EUS-nCLE image differentiation of PCLs; Clinical trial NCT02516488 ( https://clinicaltrials.gov/ct2/show/NCT02516488 )

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased mortality and readmissions in patients with heart failure (HF). The effect of in-hospital diagnosis and treatment of OSA during decompensated HF episodes remains unknown. METHODS: A single site randomized controlled trial in hospitalized patients with decompensated HF (n=150) who were diagnosed with OSA during the hospitalization. All participants received guideline directed therapy for HF decompensation. Participants were randomized to an intervention arm which received positive airway pressure (PAP) therapy during the hospitalization (n=75) and a control arm (n=75). The primary outcome was discharge left ventricular ejection fraction (LVEF). RESULTS: LVEF changed in the PAP arm from 25.5 (10.4) at baseline, to 27.3 (11.9) at discharge. In the control group, LVEF was 27.3 (11.7) at baseline and 28.8 (10.5) at conclusion. There was no significant effect on LVEF of in-hospital PAP compared to control (p = 0.84) in the intention to treat analysis. On treatment analysis in the intervention arm showed a significant increase in LVEF in participants who used PAP ≥ 3 hours per night (n=36, 48%) compared to those who used it less (p=0.01). There was a dose effect with higher hours of usage associated with more improvement in LVEF. Follow-up of readmissions after 6-months post discharge revealed a >60% decrease in readmissions for patients who used PAP ≥3 hours/night compared to those who used it less than 3 hours/night (p

Introduction Patients with thermal burns become zinc deficient due to exudative losses, increased urinary excretion, and reduction of carrier proteins which results in impaired immunity, wound healing and glucose control. Previous trials have demonstrated improved wound healing utilizing fixed zinc supplementation, but none have assessed the potential benefits associated with normalizing serum zinc concentrations. The objective of this study was to compare the impact of zinc normalization on clinical outcomes in patients with severe thermal burns. Methods This retrospective, single-center study of patients with at least 10% total body surface area (TBSA) burn and three serum zinc concentrations compared the ratio of hospital length of stay (LOS) over TBSA burned (LOS/TBSA index) between those with normal (≥60 mcg/mL) and non-normal ( Results A total of 56 patients were included for evaluation (11 normal and 45 non-normal). Burn size was 20.5% TBSA [11–29] for those with normal zinc and 27.3% [22–36] for non-normal; number of grafts for each group was 1 [0–1] vs 2 [1–3] respectively. LOS/TBSA index did not differ significantly between groups (1.10 normal vs. 1.21 non-normal, unadjusted p = 0.69; p = 0.75 adjusting for number of grafts). Time to 90% epithelialization was reduced in the normal group (27.5 vs. 57 days, p = 0.02), but this did not remain statistically significant after adjustment for %TBSA and number of grafts (p = 0.18). The groups did not differ significantly in incidence of infection or hyperglycemia in either unadjusted or adjusted analyses. Conclusions This was the first study, to our knowledge, to assess the clinical impact of normalizing serum zinc levels in patients with severe burns. Our results suggest the normalization of serum zinc levels through individualized zinc supplementation is not associated with improvement in clinical outcomes during hospitalization and therefore fixed-dose zinc supplementation without acquisition of serum zinc measurements should be considered.

Background Despite high prevalence and clinical implications of disturbed sleep during pregnancy, information on changes in sleep across pregnancy and postpartum is incomplete. Moreover, predictors of differential patterns of sleep quality across the perinatal period are poorly defined. Methods This study examined subjective sleep quality using the Pittsburgh Sleep Quality Index during each trimester of pregnancy and at 4-11 weeks postpartum among 133 women inclusive of nulliparous and multiparous African Americans and Whites. Results At any given assessment, 53%-71% of women reported poor overall sleep quality (Pittsburgh Sleep Quality Index total score > 5). Moreover, 92% reported poor overall sleep quality during at least 1 assessment, including 88% at some time during gestation. Compared to nulliparous women, multiparous women reported poorer overall sleep quality, shorter sleep duration, and poorer sleep efficiency during the first trimester; poorer overall sleep quality and longer sleep latency in the second trimester; and more frequent sleep disturbances (eg, night time and early morning awakenings) during the third trimester. Among nulliparous as well as multiparous women, specific aspects of sleep (eg, subjective sleep quality, sleep disturbances, sleep efficiency) were poorer in African American compared to White women at different time points during pregnancy. No effects of race or parity were observed on sleep parameters at postpartum. Conclusions Poor sleep quality during pregnancy as well as early postpartum is highly prevalent among both African American and White women. Both multiparous status and African American race are associated with more disturbed sleep at some time points during pregnancy. These individual differences should be considered in future research and clinical efforts to promote perinatal sleep health.

Background: Data from the 2009 influenza pandemic suggested asthma might protect from severe disease in hospitalized patients. Asthma does not appear to increase risk for hospitalization or mortality with COVID-19. Objective: This study was undertaken to see if atopy actually protected those hospitalized with COVID-19. Methods: Retrospective chart review on all patients testing positive for SARS-CoV-2 over 2 months at a major adult and pediatric tertiary referral center hospital. Charts were evaluated for history of atopic disease, as were the need for ICU admission, requirement for supplemental oxygen and/or intubation, and in hospital mortality. Results: No significant differences in outcomes for patients (n = 275) based on atopic disease were noted: ICU admission, 43% versus 44.7% (atopic versus no atopic disease, respectively; p = 0.84); supplemental oxygen use, 79.1% versus 73.6% (p = 0.36); intubation rate, 35.8% versus 36.5% (p = 0.92); and mortality rate, 13.4% versus 20.7% (p = 0.19). More patients with atopic disease had COPD listed as a diagnosis in their chart (38.8% versus 17.3%, p 0.2). Conclusion: Severity of COVID-19 in hospitalized patients does not differ based on atopic status. However, adjusting for presence of COPD led to a suggestion of possible reduced severity in patients with atopy but not asthma.

Background: Compared with patients who undergo pancreatic surgery for chronic pancreatitis and malignancy, patients with pancreatic cystic lesions (PCLs) generally have normal adjacent pancreatic parenchyma. There is a paucity of literature evaluating new-onset diabetes mellitus (NODM) following PCL resection. We sought to characterize the incidence and risk factors associated with NODM following partial pancreatectomy for PCLs. Methods: We utilized the IBM MarketScan Database (2012-2018) to identify all non-diabetic adult patients who underwent elective partial pancreatectomy for PCLs. Rigorous stepwise exclusion criteria were applied to identify patients without other pancreatic disease. We performed time-to-event analyses using Kaplan-Meier curves and multivariable Cox proportional hazards regression to define the incidence and risk factors associated with postoperative NODM. Findings: Among 311 patients with PCLs who underwent partial pancreatectomy, the overall risk of NODM was 9.1% (95% CI 6.3-12.9%), 15.1% (95% CI 11.3-20.2%), and 20.2% (95% CI 15.3-26.4%) at six, 12 and 24 months, respectively. Multivariable analysis revealed that older age (55-64 years, adjusted Hazard Ratio (aHR) 1.97, 95% CI 1.04-3.72 vs. 18-54 years), obesity (aHR 2.63, 95% CI 1.35-5.12), hypertension (aHR 1.79, 95% CI 1.01-3.17), and cardiovascular disease (aHR 2.54, 95% CI 1.02-6.28) were independent predictors of postoperative NODM. Rates of NODM were similar following distal pancreatectomy versus pancreaticoduodenectomy. Interpretation: Within two years, approximately one in five patients will develop NODM following partial pancreatectomy for PCLs. Those with advanced age, metabolic syndrome features, and/or cardiovascular disease may benefit from preoperative counselling for risk-reduction and intensive postoperative monitoring, education, and treatment strategies for DM. Funding: National Center for Advancing Translational Sciences, award number UL1TR002733. Declaration of Interests: None of the authors have any conflicts of interest or financial ties to disclose related to the current study. Ethics Approval Statement: This database is a publicly available population-based dataset. As such, the study was exempt from approval by the Ohio State University Institutional Review Board.

Purpose Asplenic patients are at increased risk for post-splenectomy infection caused by Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B (Hib), and vaccination rates against these organisms remain low. The purpose of this study was to evaluate vaccination rates before and after implementation of a pharmacist-driven electronic vaccination tracking system. Methods This retrospective cohort analysis compared adult splenectomy patients before and after implementation of a pharmacist-driven tracking system with a primary outcome of complete initial vaccination. The system included use of an i-Vent to track and communicate vaccination status and a bundled vaccination order set. Complete initial vaccination was defined as documented administration of the following vaccines: pneumococcal, meningococcal, and Hib. Secondary outcomes included complete follow-up vaccination and factors associated with incomplete vaccination. Results A total of 261 patients were included for analysis (142 pre-intervention, 119 post-intervention). The most common indication for splenectomy was malignancy (52.1% pre-intervention, 47.9% post-intervention). Complete initial vaccination rates increased by almost 10% post-intervention from 68.3% to 77.3% (p = 0.11). There was a statistically significant increase with guideline recommended pneumococcal (13-valent) as part of the initial vaccination series (p Conclusion Implementation of a pharmacist-driven electronic vaccination tracking system and bundled order set may increase rates of vaccination among asplenic patients. Although this improvement was not statistically significant, it is still clinically impactful. One limitation of the study was many outpatient oncology pharmacists were not utilizing the tracking tool at the time of data collection. Projected vaccination rates are likely higher now that more pharmacists are aware of this tool.

Background Postpartum is a period of unique psychosocial stress characterized by sleep disturbance, risk for depressed mood, and heightened parenting stress. However, data on effects of these exposures on inflammatory immune function are limited. Methods This study examined associations among sleep, psychosocial stress (i.e., parenting stress, general perceived stress), mood (i.e., depressive symptoms), serum cytokine levels, and LPS-stimulated proinflammatory cytokine production among 69 women (32 African American, 37 White) assessed at 7–10 weeks postpartum. Results No associations between behavioral measures and serum cytokine levels were observed among women of either race. In African American women, but not Whites, poorer sleep quality, greater parenting stress, and greater depressive symptoms were associated with greater LPS-stimulated IL-6 and IL-8 production (ps ≤ 0.05). Also in African Americans, greater general perceived stress was associated with greater IL-8 production, and greater depressive symptoms with greater stimulated TNF-α production (ps ≤ 0.05). Simple mediation models highlighted the bidirectional relationship between stress and sleep in relation to inflammation among African American women. Conclusions Significant effects of both stress/distress and poor sleep quality on proinflammatory cytokine production during postpartum were observed uniquely among African American women. These data are consistent with an allostatic load model which predicts that conditions of chronic stress impart vulnerability to dysregulated responses to novel stressor exposures. The bidirectional nature of the stress-sleep relationship has clinical relevance. Studies examining whether interventions focused on one or both of these psychological factors during postpartum is beneficial for inflammatory profiles would be informative. In addition, examination of these models in relation to maternal health at postpartum, including delivery related wounds and other infections, is warranted.

Background In the US, influenza vaccination is recommended annually to everyone ≥6 months. Prior receipt of influenza vaccine can dampen antibody responses to subsequent vaccination. This may have implications for pregnant women and their newborns, groups at high risk for complications from influenza infection. Objective This study examined effects of prior vaccination on maternal and cord blood antibody levels in a cohort of pregnant women in the US. Study design Influenza antibody titers were measured in 141 pregnant women via the hemagglutination inhibition (HAI) assay prior to receipt of quadrivalent influenza vaccine, 30 days post-vaccination, and at delivery (maternal and cord blood). Logistic regression analyses adjusting for age, BMI, parity, gestational age at vaccination, and year of vaccination compared HAI titers, seroprotection, and seroconversion in women with versus without vaccination in the prior year. Results Compared to those without vaccination in the previous year (n = 50), women with prior vaccination (n = 91) exhibited higher baseline antibody titers and/or seroprotection rates against all four strains after controlling for covariates. Prior vaccination also predicted lower antibody responses and seroconversion rates at one month post-vaccination. However, at delivery, there were no significant differences in antibody titers or seroprotection rates in women or newborns, and no meaningful differences in the efficiency of antibody transfer, as indicated by the ratio of cord blood to maternal antibody titers at the time of delivery. Conclusion In this cohort of pregnant women, receipt of influenza vaccine the previous year predicted higher baseline antibody titers and decreased antibody responses at one month post-vaccination against all influenza strains. However, prior maternal vaccination did not significantly affect either maternal antibody levels at delivery or antibody levels transferred to the neonate. This study is registered with the NIH as a clinical trial (NCT02148874).

Objectives To identify managerial skills required in community pharmacy practice, explore new practitioners' previous exposure to these skills, and assess new practitioners' perceived preparedness to take on managerial responsibilities. Methods A survey was developed with the use of Qualtrics and distributed by state pharmacy associations using a convenience sample of pharmacists from Iowa, Kentucky, Michigan, Ohio, and Pennsylvania. Pharmacists not practicing in a community pharmacy setting at the time of the study were excluded. New practitioners were defined as pharmacists practicing for no more than 10 years. Results A total of 168 pharmacists completed the survey. More than one-half (56%) of respondents self-reported being in a managerial position, and 90% of respondents thought that managerial skills were always or very often necessary. At graduation, 15% of respondents rated their managerial skill proficiency to be high to very high, with this increasing to 57% at current point in their career. When comparing managers versus non-managers, 78% of skills assessed showed higher utilization in managers. Interestingly, only 44% of skills showed a higher proficiency in managers. Finally, 88% of respondents thought that their managerial skills could be improved. Conclusion New practitioners in community practice reported a high utilization of managerial skills, as well as improved proficiency throughout their careers. These skills are important in both community pharmacy training and practice. Managers reported higher utilization of managerial skills, but that utilization did not always correlate with proficiency. This highlights the need to further identify and improve managerial skills during pharmacy education and as part of ongoing continuing professional development.

Background: Complementary and alternative medicine (CAM) use amongst Americans is increasingly widespread. Recent data shows that 33% of Americans have used CAM therapy in the past 12 months. The prevalence of CAM use highlights the need for pharmacists and health care providers and their respective students to be knowledgeable regarding these therapies. Objective In order to assess attitudes and perceptions of health professional faculty regarding CAM modalities, an on-line survey was developed and distributed by e-mail in 2010 to targeted participants. This study aimed to: (1) describe attitudes and perceptions of faculty regarding CAM use, and (2) assess changes in these markers since the initial 2002 survey. Design A Qualtrics ® anonymous survey link was sent to health sciences faculty listservs in 2002 and 2010. Survey questions assessed frequency of subject CAM self-use, referral frequency and CAM modalities that they felt were essential for health care education today. Results Faculty had significant increase in self-use of CAM and increased likelihood to refer for most CAM modalities (mind–body interventions (17% vs. 41%), p p p = 0.002, and energy therapies (4% vs. 9%), p = 0.03). They also considered teaching about mind–body, biologically based, and manipulative and body-based modalities an essential component of curricula. Future implications Survey data will inform research, education, and practice gaps, and be utilized to educate health professionals about CAM resources in patient care, research, and to develop didactic and experiential teaching.

Pregnancy is a period of considerable physiological adaption in neuroendocrine, cardiovascular, as well as immune function. Understanding of typical changes in inflammatory immune responses during healthy pregnancy is incomplete. In addition, despite considerable racial difference in adverse pregnancy outcomes, data are lacking on potential racial differences in such adaptation. This repeated measures prospective cohort study included 37 Black and 39 White women who provided blood samples during early, mid-, and late pregnancy and 8–10 weeks postpartum. Peripheral blood mononuclear cells were incubated with lipopolysaccharide (LPS) for 24 hours and supernatants assayed by electrochemiluminescence to quantify interleukin(IL)-6, tumor necrosis factor(TNF)-α, IL-1β, and IL-8 production. While no changes were observed in IL-8 production over time, significant increases in IL-6, TNF-α, and IL-1β production were observed from early to late pregnancy, with subsequent declines approaching early pregnancy values at postpartum (ps

Background Central sleep apnea (CSA) has a high prevalence in hospitalized patients with heart failure with reduced ejection fraction and is independently associated with increased readmissions in these patients. However, the economic impact of previously undiagnosed CSA on heart failure related readmissions remains poorly understood. Methods We used an established inception cohort of heart failure patients who had surveillance inpatient sleep testing (The OSU-Sleep Heart Program) during their hospitalization. Patients were followed up post-discharge and the number and cost of readmissions and vital status were tracked. Sleep disordered breathing (SDB) status was classified based on the sleep study into CSA, obstructive sleep apnea (OSA) or no SDB. The primary comparisons were between the CSA and no SDB groups. Results Between 2008 and 2012, 1547 consecutive patients admitted for heart failure underwent sleep studies during hospitalization. Of those, 438 patients had CSA and 393 had no SDB. The 3-month readmission rate was 33.6% for CSA and 20.4% with no SDB (p Conclusions Previously undiagnosed CSA is associated with increased readmissions in heart failure patients regardless of underlying ejection fraction. Furthermore, CSA was independently associated with increased cost of heart failure readmissions at both 3 months and 6 months. Patients with HF and CSA represent a high cost cohort of patients admitted for heart failure and can be considered a target population for potential readmission reduction interventions.

Recovery of files can be a challenging task in file system investigations, and most carving techniques are based on file signatures or semantics within the file. However, these carving techniques often only recover the files, but not the metadata associated with the file. In this paper, we propose a novel, generic approach for carving metadata by searching for equal and co-located timestamps. The rationale is that there are some common metadata for files and directories within each file system. Our generic time carver provides potential timestamp locations for repeated timestamps in each metadata structure, identifying potential metadata for files. A semantic parser then filters the results with respect to the specific file system type. In our experiments, extraction of MFT entries in NTFS and inodes in Ext4 had near perfect precision for metadata entries with multiple equivalent timestamps, and for such metadata structures we obtained perfect recall for NTFS. For known file systems, we use the information found within identified metadata to recover files, and by recovering files and their associated metadata we increase the evidential value of recovered files. https://doi.org/10.1016/j.fsidi.2020.301005 2666-2817/© 2020 The Author(s). Published by Elsevier Ltd on behalf of DFRWS. All rights reserved. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction CART-cell therapy is associated with dramatic efficacy in patients with relapsed/refractory diffuse large B-cell lymphoma and B-acute lymphoblastic leukemia. However, the efficacy of CART therapy is limited by potentially fatal toxicities including cytokine release syndrome (CRS) and neurotoxicity. Increasingly, emerging reports have suggested the potential for significant hemodynamic collapse following CART therapy. Yet, whether the occurrence of these hemodynamic shifts or any other cardiovascular disease (CVD) events have bearing on clinical outcomes after CART initiation is unknown. Methods We evaluated all patients treated with CART therapy for lymphoid malignancies at The Ohio State University James Comprehensive Cancer Center between 2016-2019 and assessed the incidence of CVD events and severe hemodynamic collapse [systolic blood pressure (SBP) cutoff of less than 80 mmHg]. We also evaluated the relationship of CVD events, hemodynamic collapse, and the presence of preceding CVD on overall survival (OS) and progression-free-survival (PFS) following infusion of CART cells utilizing univariate log-rank comparison. Results We evaluated 66 patients with 62% male and 38% female with an average age of 60 years (range 23-80). 49 (74%) patients received Yescarta and 17 (26%) patients received Kymriah. With a median follow-up time of 21 months, OS and PFS at 1 year were 72% and 43%, respectively, in concordance with previously reported ZUMA1 and JULIET survival rates. Overall, from 66 CART-treated patients, 14 (21.2%) developed incident CVD events, including 11 patients with arrhythmias and 2 with CHF. The median decrease in peak systolic blood pressure after infusion was 32 mmHg (IQR 22-47 mmHg), noted at a median of 4 days post-CART. Furthermore, after infusion, 17 (25.8%) saw falls in systolic pressure to Conclusion The development of significant early hypotension is associated with a marked decrease in survival among patients receiving CART therapy. Further understanding of this finding, and its relation to CRS is urgently needed in order to maximize the effectiveness of this novel anticancer therapy.

Adiponectin and leptin are hormones known to play roles in maternal metabolism during pregnancy. Levels of these hormones have been demonstrated to vary based on adiposity and race. However, there is a lack of data concerning the relationship between race and the change of adiponectin and leptin throughout pregnancy. The purpose of this study was to examine serum levels of adiponectin, leptin, and leptin-to-adiponectin ratio (LAR) throughout pregnancy and to assess their association with gestational weight gain (GWG) and infant birth weight while considering the effects of race and pre-pregnancy body mass index (BMI). Serum levels of adiponectin, leptin, gestational weight gain, and infant birth weight were measured in 80 pregnant women at early (12.4 ​± ​1.3 weeks gestation), mid (20.6 ​± ​1.3 weeks gestation), late pregnancy (29.2 ​± ​1.4 weeks gestation), and 7–11 weeks postpartum (8.8 ​± ​0.8 weeks). In women overall, serum adiponectin decreased across pregnancy and increased at postpartum (p ​= ​0.17.) At each prenatal timepoint, both black race and obesity were associated with lower adiponectin (ps ​

Imaging patterns from endoscopic ultrasound (EUS)-guided needle-based confocal laser endomicroscopy (nCLE) have been associated with specific pancreatic cystic lesions (PCLs). We compared the accuracy of EUS with nCLE in differentiating mucinous from nonmucinous PCLs with that of measurement of carcinoembryonic antigen (CEA) and cytology analysis.We performed a prospective study of 144 consecutive patients with a suspected PCL (≥20 mm) who underwent EUS with fine-needle aspiration of pancreatic cysts from June 2015 through December 2018 at a single center; 65 patients underwent surgical resection. Surgical samples were analyzed by histology (reference standard). During EUS, the needle with the miniprobe was placed in the cyst, which was analyzed by nCLE. Fluid was aspirated and analyzed for level of CEA and by cytology. We compared the accuracy of nCLE in differentiating mucinous from nonmucinous lesions with that of measurement of CEA and cytology analysis.The mean size of dominant cysts was 36.4 ± 15.7 mm and the mean duration of nCLE imaging was 7.3 ± 2.8 min. Among the 65 subjects with surgically resected cysts analyzed histologically, 86.1% had at least 1 worrisome feature based on the 2012 Fukuoka criteria. Measurement of CEA and cytology analysis identified mucinous PCLs with 74% sensitivity, 61% specificity, and 71% accuracy. EUS with nCLE identified mucinous PCLs with 98% sensitivity, 94% specificity, and 97% accuracy. nCLE was more accurate in classifying mucinous vs nonmucinous cysts than the standard method (P.001). The overall incidence of postprocedure acute pancreatitis was 3.5% (5 of 144); all episodes were mild, based on the revised Atlanta criteria.In a prospective study, we found that analysis of cysts by nCLE identified mucinous cysts with greater accuracy than measurement of CEA and cytology analysis. EUS with nCLE can be used to differentiate mucinous from nonmucinous PCLs. ClincialTrials.gov no: NCT02516488.

Background: A growing population of young soldiers returning from military conflict and civilians suffering from diabetes, peripheral vascular disease, and cancer contribute to the nearly two million people living with limb loss in the United States alone. A surprising majority of amputees suffer from chronic pain in the form of unpredictable neuroma-related residual limb and phantom limb pain. These conditions profoundly decrease patient function and quality of life, and despite a myriad of proposed therapies, there are no reliable treatment or prevention strategies for postamputation pain. Targeted muscle reinnervation (TMR) surgically transfers amputated nerves to redundant motor nerves to allow for physiologic nerve healing. In this study, TMR was proposed for prevention of postamputation pain. Methods: Immediate TMR was performed in 51 patients undergoing major limb amputation as a preemptive measure for symptomatic neuromas and phantom limb phenomena at two centers. Pain outcomes were assessed using an eleven-point Numerical Rating Scale (NRS) and the Patient-Reported Outcomes Measurement Information System (PROMIS), and were compared to a cross-section of 438 untreated amputee controls. Opioid prescription patterns were secondarily collected for TMR patients. Findings: Patients undergoing TMR concurrently at the time of major limb amputation had less phantom limb and residual limb pain compared to untreated amputee controls across all subgroups and by all measures. Median "worst pain in the past 24 hours" for the TMR cohort was 1 out of 10 compared to 5 (phantom) and 4 (residual) out of 10 in the general amputee population for phantom and residual limb pain (p=0.003 and p

Though typically mild, side effects to the influenza virus vaccine are common and may contribute to negative perceptions including the belief that the vaccine can cause the flu. However, the extent to which subjective symptoms correspond with biological response indicators is poorly understood.This study examined associations among subjective side effects (soreness at the site of injection and illness-like symptoms), serum proinflammatory cytokines and body temperature a baseline, 1, 2, and 3 days following receipt of trivalent inactivated influenza vaccine (IIV3) in a sample of 56 women 18-40 years in age.In relation to local reactions, women reporting being very sore at the injection site at 1 day post-vaccination exhibited greater increases in serum TNF-α and MIF in the days following vaccination compared to those with no or mild soreness. In addition, higher basal body temperature was observed in this group compared to other groups (98.7°F versus 98.0-98.1°). In relation to systemic reactions, women endorsing illness-like symptoms (headache, fatigue, nausea, sore throat, dizziness, achiness, or mild fever) exhibited marginally higher IL-6 at baseline (p=0.055) and greater increases in serum MIF at 2 days post-vaccination than those reporting no systemic symptoms. Associations of systemic symptoms with inflammatory responses were not accounted for by concomitant local reactions. As expected, antibody responses to the vaccine were highly similar in women regardless of local or systemic symptoms.These results are consistent with the notion that subjective reports of local and systemic reactions following vaccination may be predicted by and correspond with biological indicators of inflammatory status, but are not meaningful predictors of antibody responses. To improve adherence to vaccine recommendations, clinicians should provide assurance that such symptoms may be related to normal mild inflammatory responses to the vaccine and do not reflect immunogenicity.

Objectives To determine dosing alert rates based on prescription order characteristics and identify prescription order risk factors for the occurrence of dosing alerts. Methods A retrospective analysis of inpatient medication orders and dosing alerts occurring during October 2011 and January, April, and July 2012 at a pediatric institution. Prescription orders and alerts were categorized by: medication class, patient age, route of administration, and month of the year. Results There were 228,259 orders during the studied period, with 11,072 alerted orders (4.9%). The most frequently alerted medication class was the non-analgesic central nervous system agent class (14% of alerts). Age, route, medication class, and month all independently affected dosing alert rates. The alert rate was highest for immunosuppressive agents (54%), neonates (6.7%), and orders for rectal administration (9.5%). The alert rate was higher in adult patients receiving their care at a pediatric institution (5.7%) compared to children (4.7%), but after multivariate analysis, pediatric orders had higher odds for an alert (OR 1.1, 95% CI 1.05–1.16). Mercaptopurine had the highest alert rate when categorized by active ingredient (73.9%). Albuterol 2.5 mg/mL continuous aerosol and heparin 1000 units in 0.9% sodium chloride injection solution were the unique medications with the highest alert rates (100.0% and 97.7%, respectively). Conclusions Certain types of prescription orders have a higher risk for causing dosing alerts than others. Patient age, medication class, route of administration, and the month of year can affect dosing alert rates. Design and customization efforts should focus on these medications and prescription order characteristics that increase the risk for dosing alerts.

The mechanism of vascular endothelial dysfunction (VED) and cardiovascular disease in obstructive sleep apnea (OSA) is unknown. We performed a comprehensive evaluation of endothelial nitric oxide synthase (eNOS) function directly in the microcirculatory endothelial tissue of OSA patients who have very low cardiovascular risk status. Nineteen OSA patients underwent gluteal biopsies before, and after effective treatment of OSA. We measured superoxide (O2(•-)) and nitric oxide (NO) in the microcirculatory endothelium using confocal microscopy. We evaluated the effect of the NOS inhibitor l-Nitroarginine-Methyl-Ester (l-NAME) and the NOS cofactor tetrahydrobiopterin (BH4) on endothelial O2(•-) and NO in patient endothelial tissue before and after treatment. We found that eNOS is dysfunctional in OSA patients pre-treatment, and is a source of endothelial O2(•-) overproduction. eNOS dysfunction was reversible with the addition of BH4. These findings provide a new mechanism of endothelial dysfunction in OSA patients and a potentially targetable pathway for treatment of cardiovascular risk in OSA.

Objectives To (1) determine awareness of the Board of Pharmacy Specialties (BPS) certification by current student pharmacists at all levels of pharmacy education, (2) evaluate student perceptions of effective educational formats for learning about BPS certification, and (3) assess students’ interest in obtaining BPS certification in future careers. Participants State boards of pharmacy in all states were contacted to request licensed intern contact information; all students with valid e-mail addresses were invited to participate. Main outcome measures were as follows: participants were asked about awareness of BPS certification, where they learned about certification, interest in attaining certification, and demographics. Results Overall, 1108 (15.3%) survey responses were included for analysis representing students from schools of pharmacy across the country. A majority of respondents (73.2%; n = 750) were aware of BPS certification and identified learning about BPS most from faculty members ( n = 509) and preceptors ( n = 289), primarily in required courses ( n = 311) and advanced pharmacy practice experiences ( n = 238). When asked about future plans, 43.3% ( n = 472) stated they were likely to pursue BPS certification, 41.1% ( n = 449) were undecided, and 15.6% unlikely ( n = 170). Conclusion Most respondents were aware of BPS certification, learning the most through didactic and experiential activities, and many indicated they are likely to or undecided about pursuing BPS certification. Respondents unaware of or undecided about BPS certification represent an opportunity for colleges of pharmacy and professional organizations to formalize their role in student education about BPS and advocacy efforts.

The maternal immune system undergoes substantial changes to support healthy pregnancy. Although obesity is a primary driver of inflammation and predictive of perinatal complications, additive effects of pregnancy and obesity on changes in inflammatory processes are not well delineated.This study examined serum proinflammatory markers interleukin(IL)-6, IL-8, tumor necrosis factor (TNF)-α, IL-1β, and C-reactive protein (CRP) during each trimester of pregnancy and 4-6 weeks postpartum among 57 women.Overall, IL-6 showed an increasing trend across pregnancy and significant increase at postpartum. Similarly, TNF-α increased significantly across gestation, with a further increase at postpartum. Both IL-8 and IL-1β showed a U-shaped curve, decreasing from early to later pregnancy, and increasing at postpartum. Finally, serum CRP decreased significantly across pregnancy, with further decreases at postpartum. Maternal obesity predicted higher IL-6 at each study visit. Obese women showed a trend toward elevated serum CRP during pregnancy, and significantly higher levels at postpartum.The course of pregnancy and postpartum is characterized by significant changes in serum proinflammatory mediators. Obese women show elevations in serum proinflammatory markers relative to normal weight women during pregnancy and postpartum. Further research is needed to determine the extent to which obesity-induced inflammation affects maternal and fetal health.

Adverse pregnancy outcomes, including preterm birth, are markedly higher among African-Americans versus Whites. Stress-induced immune dysregulation may contribute to these effects. Epstein-Barr virus (EBV) reactivation provides a robust model for examining cellular immune competence. This study examined associations of EBV virus capsid antigen immunoglobulin G (VCA IgG) with gestational stage, race, and racial discrimination in women during pregnancy and postpartum.Fifty-six women (38 African-American, 18 White) were included. African-Americans and Whites did not differ in age, education, income, parity, or body mass index (ps ≥ .51). During the 1st, 2nd, and 3rd trimester and ~5 weeks postpartum, women completed measures of racial discrimination, perceived stress, anxiety, depressive symptoms and health behaviors. EBV VCA IgG antibody titers were measured via ELISA in serum collected at each visit.In the overall sample, EBV VCA IgG antibody titers were lower in the 3rd versus 1st trimester (p=.002). At every timepoint (1st, 2nd, 3rd trimester and postpartum), African-American women exhibited higher serum EBV VCA IgG antibody titers than Whites (ps.001). This effect was most pronounced among African-Americans reporting greater racial discrimination [p=.03 (1st), .04 (2nd), .12 (3rd), .06 (postpartum)]. Associations of race and racial discrimination with EBV VCA IgG antibody titers were not accounted for by other measures of stress or health behaviors.Compared to Whites, African-American women showed higher EBV VCA IgG antibody titers, indicative of impaired cellular immune competence, across pregnancy and postpartum. This effect was particularly pronounced among African-American women reporting greater racial discrimination, supporting a role for chronic stress in this association. In women overall, EBV antibody titers declined during late as compared to early pregnancy. This may be due to pregnancy-related changes in cell-mediated immune function, humoral immune function, and/or antibody transfer to the fetus in late gestation. As a possible marker of stress-induced immune dysregulation during pregnancy, the role of EBV reactivation in racial disparities in perinatal health warrants further attention.

Background Hospitalized heart failure patients have a high readmission rate. We sought to determine the independent risk due to central sleep apnea (CSA) of readmission in patients with systolic heart failure (SHF). Methods and Results This was a prospective observational cohort study of hospitalized patients with SHF. Patients underwent sleep studies during their hospitalization and were followed for 6 months to determine their rate of cardiac readmissions; 784 consecutive patients were included; 165 patients had CSA and 139 had no sleep-disordered breathing (SDB); the remainder had obstructive sleep apnea (OSA). The rate ratio for 6 months' cardiac readmissions was 1.53 (95% confidence interval 1.1–2.2; P = .03) in CSA patients compared with no SDB. This rate ratio was adjusted for systolic function, type of cardiomyopathy, age, weight, sex, diabetes, coronary disease, length of stay, admission sodium, creatinine, hemoglobin, blood pressure, and discharge medications. Severe OSA was also an independent predictor of readmissions with an adjusted rate ratio of 1.49 ( P = .04). Conclusion In this first evaluation of the impact of SDB on cardiac readmissions in heart failure, CSA was an independent risk factor for 6 months' cardiac readmissions. The effect size of CSA exceeded that of all known predictors of heart failure readmissions.

In the U.S., seasonal trivalent influenza virus vaccine (TIV) is currently universally recommended for all pregnant women. However, data on the maternal inflammatory response to vaccination is lacking and would better delineate the safety and clinical utility of immunization. In addition, for research purposes, vaccination has been used as a mild immune trigger to examine in vivo inflammatory responses in nonpregnant adults. The utility of such a model in pregnancy is unknown. Given the clinical and empirical justifications, the current study examined the magnitude, time course, and variance in inflammatory responses following seasonal influenza virus vaccination among pregnant women.Women were assessed prior to and at one day (n=15), two days (n=10), or approximately one week (n=21) following TIV. Serum interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP), and macrophage migration inhibitory factor (MIF) were determined by high sensitivity immunoassay.Significant increases in CRP were seen at one and two days post-vaccination (ps05). A similar effect was seen for TNF-α, for which an increase at two days post-vaccination approached statistical significance (p=.06). There was considerable variability in magnitude of response; coefficients of variation for change at two days post-vaccination ranged from 122% to 728%, with the greatest variability in IL-6 responses at this timepoint.Trivalent influenza virus vaccination elicits a measurable inflammatory response among pregnant women. There is sufficient variability in response for testing associations with clinical outcomes. As adverse perinatal health outcomes including preeclampsia and preterm birth have an inflammatory component, a tendency toward greater inflammatory responding to immune triggers may predict risk of adverse outcomes, providing insight into biological mechanisms underlying risk. The inflammatory response elicited by vaccination is substantially milder and more transient than seen in infectious illness, arguing for the clinical value of vaccination. However, further research is needed to confirm that the mild inflammatory response elicited by vaccination is benign in pregnancy.

Summary Objective Self-rated health is a strong independent predictor of mortality after accounting for objective health status, behavioral risk factors, and sociodemographic characteristics. However, mechanisms underlying this association are largely unexplained. Inflammation has been associated with increased risk of morbidity and mortality in the elderly. The current study aimed to: (1) examine associations between self-rated health and serum inflammatory markers in older adults; (2) examine the relative strength of these associations for self-rated health versus self-rated change in recent health; (3) examine components of self-rated health that may underlie the association between inflammation and global self-rated health. Methods Self-rated health, as measured by the RAND health survey, and serum interleukin (IL)-6 and C-reactive protein (CRP) were assessed among 250 generally healthy older adults (185 women, 65 men; average age = 63.8 ± 13.7 years). Results A series of linear regression analyses demonstrated that poorer self-rated health was significantly associated with higher IL-6 and CRP. These relationships remained after controlling for age, body mass index, gender, and objective health conditions. These associations also remained after controlling for depressive symptoms, neuroticism, perceived change in health over the past year, and health behaviors (smoking, sleep quality, and physical activity). Analyses of RAND component measures demonstrated that poorer physical functioning was significantly associated with IL-6; the relationship between global self-rated health and both IL-6 and CRP remained after accounting for perceived physical functioning. Conclusions Poorer self-rated health is associated with elevated serum inflammatory markers among generally healthy older adults. The relationship of self-rated health with inflammatory markers is not secondary to depressive symptoms, neuroticism, or recent changes in perceived health. Subjective ratings of health provide important clinical information regarding inflammatory status, beyond traditional objective risk factors, even among generally healthy individuals.