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Introduction Acute pancreatitis (AP) occurs among patients with pancreas-sufficient cystic fibrosis (PS-CF) but is reportedly less common among patients with pancreas-insufficient cystic fibrosis (PI-CF). The incidence of AP may be influenced by cystic fibrosis transmembrane conductance regulator (CFTR) modulator use. We hypothesized that CFTR modulators would reduce AP hospitalizations, with the greatest benefit in PS-CF. Methods MarketScan (2012-2018) was queried for AP hospitalizations and CFTR modulator use among patients with CF. Multivariable Poisson models that enabled crossover between CFTR modulator treatment groups were used to analyze the rate of AP hospitalizations on and off therapy. Pancreas insufficiency was defined by the use of pancreas enzyme replacement therapy. Results A total of 10,417 patients with CF were identified, including 1,795 who received a CFTR modulator. AP was more common in PS-CF than PI-CF (2.9% vs 0.9%, P = 0.007). Overall, the observed rate ratio of AP during CFTR modulator use was 0.33 (95% confidence interval [CI] 0.10, 1.11, P = 0.07) for PS-CF and 0.38 (95% CI 0.16, 0.89, P = 0.03) for PI-CF, indicating a 67% and 62% relative reduction in AP hospitalizations, respectively. In a subset analysis of 1,795 patients who all had some CFTR modulator use, the rate ratio of AP during CFTR modulator use was 0.36 (95% CI 0.13, 1.01, P = 0.05) for PS-CF and 0.53 (95% CI 0.18, 1.58, P = 0.26) for PI-CF. Discussion CFTR modulator use is associated with a reduction in AP hospitalizations among patients with CF. These observational data support the prospective study of CFTR modulators to reduce AP hospitalizations among patients with CF.

Introduction Despite the increasing availability of advanced endoscopic resections and its favorable safety profile, surgery for nonmalignant colorectal polyps has continually increased. We sought to evaluate readmission rates and outcomes of elective surgery for nonmalignant colorectal polyps on a national level in the United States. Methods The Nationwide Readmissions Database (2010-2014 [International Classification of Diseases, Ninth Revision] and 2016-2018 [International Classification of Diseases, 10th Revision]) was used to identify all adult subjects (age ≥18 years) who underwent elective surgical resection of nonmalignant colorectal polyps. Multivariable analyses were performed for predictors of postoperative morbidity and 30-day readmission. Results Elective surgery for nonmalignant colorectal polyps was performed in 108,468 subjects from 2010 to 2014 and in 54,956 subjects from 2016 to 2018, most of whom were laparoscopic. Postoperative morbidity and 30-day readmission rates were 20.5% and 8.5% from 2010 to 2014, and 13.0% and 7.6% from 2016 to 2018, respectively. Index admission mortality rates were 0.3-0.4%; mortality rates were higher in those with postoperative morbidity. Multivariable analyses revealed that male sex, ≥3 comorbidities, insurance status, and open surgery predicted an increased risk of both postoperative morbidity and 30-day readmission. In addition, postoperative morbidity (2010-2014 [odds ratio 1.58; 95% confidence interval 1.44-1.74] and 2016-2018 [odds ratio 1.55; 95% confidence interval 1.37-1.75]) predicted early readmission. Discussion In this investigation of national practices, elective surgery for nonmalignant colorectal polyps remains common. There is considerable risk of adverse postoperative outcomes, which highlights the importance of increasing awareness of the range of endoscopic resections and referring subjects to expert endoscopy centers.

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 18 F‐Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) positive (PET+) cytologically indeterminate thyroid nodules (ITNs) have variable cancer risk in the literature. The benign call rate (BCR) of Afirma Gene Classifier (Gene Expression Classifier, GEC, or Genome Sequence Classifier, GSC) in (PET +) ITNs is unknown. Methods This is a retrospective study at our institution of all patients with (PET+) ITNs (Bethesda III/IV) from 1 January 2010 to 21 May 2019 who underwent Afirma testing and/or surgery or repeat FNA with benign cytology. Results Forty‐five (PET+) ITNs were identified: 31 Afirma‐tested (GEC = 20, GSC = 11) and 14 either underwent surgery (n = 13) or repeat FNA (Benign cytology) (n = 1) without Afirma. The prevalence of cancer and noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP) including only resected nodules and ITN with repeat benign FNA (n = 33) was 36.4% (12/33). Excluding all Afirma “suspicious” non‐resected ITNs and assuming all Afirma “benign” ITNs were truly benign, that prevalence was 28.6% (12/42). The BCR with GSC was 64% compared to 25% with GEC (p = 0.056). Combining GSC/GEC‐tested ITNs, the BCR was higher in ITNs demonstrating low/very low‐risk sonographic pattern by the American Thyroid Association (ATA) classification and ITNs scoring, In this study, the prevalence of cancer and noninvasive follicular thyroid neoplasm with papillary‐like nuclear features in PET positive cytologically indeterminate thyroid nodules was 28.6–36.4% depending on the method of calculation. The benign call rate of Afirma GSC in these nodules was 64%. When combining Afirma GEC/GSC tested PET positive cytologically indeterminate thyroid nodules, the benign call rate was higher in nodules with a lower risk sonographic pattern.

Chronic pancreatitis (CP) is a progressive disease that leads to eventual loss of endocrine and exocrine function. Total pancreatectomy and islet autotransplantation (TPIAT) is a treatment option for patients with CP; however, predicting postoperative metabolic outcomes remains elusive. In this single-center retrospective study, we report pre-TPIAT characteristics, beta cell function indices, islet yield, and post-TPIAT glucose management data to further understand their relationship. Islet yield, glucose level, and insulin requirement for 72 hours postoperatively were collected for a total of 13 TPIAT recipients between 9-2013 and 9-2018. In addition, their glucose control and basal insulin requirements at 3, 6, and 12 months post-TPIAT were analyzed. All 13 subjects had normal baseline fasting glucose levels. Median islet yield was 4882 IEq/kg (interquartile range 3412 to 8987). Median postoperative total insulin requirement on day 3 was 0.43 units/kg. Pre-TPIAT baseline glucose, insulin, or c-peptide level did not have a significant correlation with the islet yield. Similarly, there was no correlation between islet yield and insulin requirement at 72-hour postoperatively. However, there was an inverse correlation between the absolute islet yield (IEq) and insulin requirement at 6 months and 12 months following post-TPIAT. Further analysis of the relationship between 72-hour post-op insulin requirement and insulin requirement at discharge, 3, 6, and 12 months showed a positive correlation. Despite the finding of inverse correlation of islet yield with long-term basal insulin requirement, this study was not able to detect a correlation between the preoperative parameters to postoperative short-term or long-term outcome as noted in other studies. The 72-hour postoperative insulin requirement is a helpful postoperative predictor of patients needing long-term insulin management following TPIAT. This observation may identify a high-risk group of patients in need of more intensive diabetes education and insulin treatment prior to hospital discharge.

Colorectal cancer incidence is rising in adults

BackgroundChimeric antigen receptor T-cell (CAR-T) infusion is associated with early toxicity. Yet, whether early toxicity development holds ramifications for long-term outcomes is unknown.MethodsFrom a large cohort of consecutive adult patients treated with CAR-T therapies for relapsed or refractory lymphomas from 2016 to 2019, we assessed progression-free survival (PFS), by toxicity development (cytokine release syndrome (CRS), neurotoxicity, or cardiotoxicity]. We also assessed the relationship of toxicity development to objective disease response, and overall survival (OS). Multivariable regression was utilized to evaluate relationships between standard clinical and laboratory measures and disease outcomes. Differences in outcomes, by toxicity status, were also assessed via 30-day landmark analysis. Furthermore, we assessed the effects of early anti-CRS toxicity therapy use (at ≤grade 2 toxicity) on maximum toxicity grade observed, and long-term disease outcomes (PFS and OS).ResultsOverall, from 102 CAR-T-treated patients, 90 were identified as treated with single-agent therapy, of which 88.9% developed toxicity (80 CRS, 41 neurotoxicity, and 17 cardiotoxicity), including 28.9% with high-grade (≥3) events. The most common manifestations were hypotension at 96.6% and fever at 94.8%. Among patients with cardiac events, there was a non-significant trend toward a higher prevalence of concurrent or preceding high-grade (≥3) CRS. 50.0% required tocilizumab or corticosteroids. The median time to toxicity was 3 days; high grade CRS development was associated with cardiac and neurotoxicity. In multivariable regression, accounting for disease severity and traditional predictors of disease response, moderate (maximum grade 2) CRS development was associated with higher complete response at 1 year (HR: 2.34; p=0.07), and longer PFS (HR: 0.41; p=0.02, in landmark analysis), and OS (HR: 0.43; p=0.03). Among those with CRS, relative blood pressure (HR: 2.25; p=0.004), respectively, also associated with improved PFS. There was no difference in disease outcomes, or maximum toxicity grade (CRS, neurotoxicity, or cardiotoxicity) observed, based on the presence or absence of the use of early CRS-directed therapies.ConclusionsAmong adult lymphoma patients, moderate toxicity manifest as grade 2 CRS after CAR-T infusion may associate with favorable clinical outcomes. Further studies are needed to confirm these findings.

Ibrutinib is associated with dramatic efficacy against B-cell malignancies. Yet, ibrutinib is linked with potentially-limiting cardiotoxicity, including emerging reports of profound hypertension. However, the long-term incidence, severity, and impacts of hypertension development during ibrutinib-use are unknown. Therefore, from 562 consecutive patients treated with ibrutinib for B-cell malignancies between 2009-2016 we assessed the incidence of new/incident or worsened hypertension [systolic blood pressure (BP) cutoff of 130mmHg]. Observed incident-hypertension rates were compared to Framingham-heart predicted incident-hypertension rates. We also evaluated the relationship of hypertension on ibrutinib to the development of other major-adverse-cardiovascular-events (MACE), including arrhythmias, myocardial infarction, stroke, heart failure, and cardiovascular death. Further, we assessed the preventative and modulatory effects of antihypertensives, by medication-class, on ibrutinib-related hypertension. Overall, 78.3% of ibrutinib-users developed new or worsened hypertension [mean systolic BP increase 5.2mmHg ({plus minus}20.7)] over a median of 30months. New hypertension developed in 71.6% of ibrutinib-users (467 observed vs. 39 Framingham-predicted cases per 1,000 person-years), with a time-to-50% cumulative incidence of 4.2months. Among those without preceding hypertension, 17.7% developed high-grade (BP g160/100mmHg) hypertension. In multivariable regression containing known predictors of MACE, new or worsened hypertension was associated with increased MACE [hazard ratio (HR) 2.17, 95%CI 1.08-4.38]. No single-antihypertensive class was associated with prevention or control of ibrutinib-related hypertension. However, antihypertensive initiation was associated with a lower risk of MACE (HR 0.40, CI 0.24-0.66). Collectively, these data suggest ibrutinib is associated with substantial increase in the incidence and severity of hypertension, and that hypertension development may suggest a higher risk of subsequent cardiotoxic events.

Evolving epidemiological data, backed by mechanistic evidence, supports a paradoxical increase in the risk of colorectal cancer after Roux-en-Y gastric bypass surgery (RYGB). We examined the risk of colonic polyps after RYGB. A single-center retrospective study included colonoscopies performed between the years 1994 and 2018. To focus on the long-term impact of RYGB on precancerous colonic polyps, we compared patients at average risk for CRC who underwent colonoscopy ≥ 5 years after RYGB (n = 86) versus pre-RYGB (n = 106). We analyzed our data using inverse probability of treatment weighting (IPTW) using propensity scores in order to account for multiple potential confounders. After IPTW, we found no statistical differences between pre- and post-RYGB patients for risk of any polyp (33.2% pre- vs. 32.7% post-RYGB). However, the percentage of serrated polyps was higher ≥ 5 years post-RYGB compared with pre-RYGB (8.7% vs. 2.1%, p = 0.04, relative risk = 4.22; 95% CI 0.97, 18.4). Body mass index ≥ 30 kg/m2 at time of colonoscopy was associated with a greater risk for any polyp after RYGB (OR 6.23; 95% CI 1.16, 33.41). There was also a trend towards increased risk of polyps in post-RYGB patients who were current smokers (OR = 4.97; 95% CI 0.82, 30) or with age > 55 years (OR = 2.49; 95% CI 0.88, 7.00). Our data suggest that RYGB is associated with an increased risk of serrated polyps after 5 years from surgery. Prospective studies defining this risk and examining mechanisms will be instrumental for application of CRC preventative strategies in this population.

Background: The Afirma Gene Expression Classifier (GEC) has been used to further characterize cytologically indeterminate (cyto-I) thyroid nodules into either benign or suspicious categories. However, its relatively low positive predictive value (PPV) limited its use as a classifier for patients with suspicious results. The Afirma Gene Sequencing Classifier (GSC) was developed to improve PPV while maintaining a high negative predictive value (NPV), yet real-world assessment of its performance is lacking. Methods: We analyzed all patients who had cyto-I nodules and molecular testing with either GEC or GSC between 2011 and 2018 at a single academic medical center. Clinical information was obtained for 343 GEC-tested nodules and 164 GSC-tested nodules. Results: The GSC had a statistically significant higher benign call rate (76.2% vs. 48.1%, p

The number of individuals who succumb to thyroid cancer has been increasing and those who are refractory to standard care have limited therapeutic options, highlighting the importance of developing new treatments for patients with aggressive forms of the disease. Mutational activation of MAPK signaling, through BRAF and RAS mutations and/or gene rearrangements, and activation of PI3K signaling, through mutational activation of PIK3CA or loss of PTEN, are well described in aggressive thyroid cancer. We previously reported overactivation and overexpression of p21-activated kinases (PAKs) in aggressive human thyroid cancer invasive fronts and determined that PAK1 functionally regulated thyroid cancer cell migration. We reported mechanistic crosstalk between the MAPK and PAK pathways that are BRAF-dependent but MEK independent, suggesting that PAK and MEK inhibition might be synergistic. In the present study, we tested this hypothesis. Pharmacologic inhibition of group I PAKs using two PAK kinase inhibitors, G-5555 or FRAX1036, reduced thyroid cancer cell viability, cell cycle progression and migration and invasion, with greater potency for G-5555. Combination of G-5555 with vemurafenib was synergistic in BRAFV600E-mutated thyroid cancer cell lines. Finally, G-5555 restrained thyroid size of BRAFV600E-driven murine papillary thyroid cancer by >50% (P P = 0.0167), despite maintenance of MAPK activity. Taken together, these findings suggest both that group I PAKs may be a new therapeutic target for thyroid cancer and that PAK activation is functionally important for BRAFV600E-mediated thyroid cancer development.

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.

Pazopanib (PAZ), a tyrosine kinase inhibitor used in the treatment of soft tissue sarcoma (STS), should not be administered with acid‐suppressive medications (ASMs) due to decreased drug solubility. Common practice for patients requiring ASM with PAZ is to separate administration by 12 hours; however, there is little real‐world evidence describing clinical outcomes using this strategy. The aim of this study was to determine whether concomitant ASM impacted efficacy and adverse event rates in patients with STS receiving PAZ. Medical records were retrospectively reviewed for patients with STS who received PAZ from June 2011 to July 2017. Patients were stratified into two groups, PAZ with or without ASM (PAZ + ASM or PAZ only). The primary objective was to determine whether progression‐free survival (PFS) differed between groups. Secondary objectives were to determine overall survival (OS) and occurrence of grade 3/4 toxicities. Ninety‐one patients were included in the study, 42 patients in the PAZ + ASM group and 49 in the PAZ only group. Median PFS was significantly shorter in the PAZ + ASM group than the PAZ only group (5.3 vs. 6.7 months). The PAZ + ASM group also had a 74% higher relative risk of progression or death than the PAZ only group, but there was no difference in OS. Regarding adverse events, the PAZ + ASM group trended toward lower levels of grade 3/4 hypertension (19% vs. 37%). These results suggest that ASM should be avoided in patients with STS receiving PAZ. Larger studies are needed to further elucidate the impact of ASM use with PAZ in clinical practice.

Oxandrolone has proven benefits in thermal burn injury and has become a standard of care. Transaminitis is the most frequent side effect of oxandrolone use, although no risk factors have been identified that increase the risk of transaminitis. The objective was to evaluate the frequency of transaminitis while on oxandrolone and to identify risk factors leading to an increased risk of transaminitis in adult burn patients. This multicenter retrospective risk factor analysis compared two patient groups with and without occurrence of transaminitis, which was detected by an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >100 mg/dL. Secondary outcomes included percentage increase from baseline for AST/ALT, length of stay, and mortality. After univariable analysis, a multivariable logistic regression analysis was performed to detect possible risk factors leading to transaminitis. A total of 309 patients were included, with transaminitis occurring in 128 patients (41.4%) after 13 (interquartile range [IQR] 8–23) days on oxandrolone. After multivariable analysis, age (odds ratio [OR] 0.91; 95% confidence interval [CI] 0.84–0.99 for a 5-year increase in age), intravenous vasopressor use (OR 1.85; 95% CI 1.05–3.27), and amiodarone use (OR 2.51; 95% CI 1.09–5.77) were independent predictors of transaminitis, controlling for TBSA%. Transaminitis was not significantly associated with length of stay or mortality after adjusting for age and TBSA%. We conclude that patients who are younger and have concurrent amiodarone or vasopressor use have the highest risk of developing oxandrolone induced transaminitis and should be monitored closely.

Early readmission in patients with decompensated liver cirrhosis leads to an enormous burden on health care use. A retrospective cohort study using the 2013 and 2014 Nationwide Readmission Database (NRD) was conducted. Patients with a diagnoses of cirrhosis and at least one feature of decompensation were included. The primary outcome was to develop a validated risk model for early readmission. Secondary outcomes were to study the 30-day all-cause readmission rate and the most common reasons for readmission. A multivariable logistic regression model was fit to identify predictors of readmissions. Finally, a risk model, the Mumtaz readmission risk score, was developed for prediction of 30-day readmission based on the 2013 NRD and validated on the 2014 NRD. A total of 123,011 patients were included. The 30-day readmission rate was 27%, with 79.6% of patients readmitted with liver-related diagnoses. Age65 years; Medicare or Medicaid insurance; nonalcoholic etiology of cirrhosis; ≥3 Elixhauser score; presence of hepatic encephalopathy, ascites, variceal bleeding, hepatocellular carcinoma, paracentesis, or hemodialysis; and discharge against medical advice were independent predictors of 30-day readmission. This validated model enabled patients with decompensated cirrhosis to be stratified into groups with low (20%), medium, (20%-30%), and high (30%) risk of 30-day readmissions. Conclusion: One third of patients with decompensated cirrhosis are readmitted within 30 days of discharge. The use of a simple risk scoring model with high generalizability, based on demographics, clinical features, and interventions, can bring refinement to the prediction of 30-day readmission in high-risk patients; the Mumtaz readmission risk score highlights the need for targeted interventions in order to decrease rates of readmission within this population.

While cholecystectomy (CCY) is the standard of care for gallstone-related acute cholecystitis, percutaneous cholecystostomy-tube (CCYT-tube) is an alternative option in patients with significant comorbid conditions. We sought to identify immediate and longitudinal hospital outcomes of patients who underwent CCYT-tube placement and determine predictors of CCYT-tube placement and eventual CCY on a national level in the US. We identified all adults (age ≥ 18 years) with a primary diagnosis of acute calculous cholecystitis from January to November 2013 in the Nationwide Readmissions Database (NRD). The NRD allows longitudinal follow-up of a patient for one calendar year. Outcomes of patients undergoing CCY and CCYT-tube were compared. Separate univariable and multivariable regression analyses were performed to identify predictors of CCYT-tube placement and failure to undergo subsequent CCY. A total of 181,262 patients had an index hospitalization with acute cholecystitis where 178,095 (98.3%) patients underwent only CCY and 3167 (1.7%) patients were managed with CCYT-tubes. Among patients with CCYT-tube, 1196 (37.8%) underwent eventual CCY in 2013, while 1971 (62.2%) did not. One in five patients with CCYT-tube were readmitted within 30 days of hospital discharge. Multivariable analysis demonstrated that increasing age, male gender, coronary artery disease, cirrhosis, atrial fibrillation, diastolic congestive heart failure, and sepsis were associated with CCYT-tube placement. Longitudinal follow-up revealed that older age (OR 1.16, 95% CI 1.09–1.23), Elixhauser comorbidity score 3–4 (OR 1.94, 95% CI 1.03–3.63), cirrhosis (OR 3.28, 95% CI 1.59–6.79), and diastolic congestive heart failure (OR 2.47, 95% CI 1.33–4.60) were associated with failure to undergo subsequent CCY. In this national survey, nearly two in three patients who receive CCYT-tube for acute cholecystitis do not get CCY during longitudinal data capture within the same calendar year. Future research needs to target novel options for drainage of the gallbladder in high-risk patient populations.

Acute calculous cholecystitis (ACC) is frequently seen in cirrhotics, with some being poor candidates for initial cholecystectomy. Instead, these patients may undergo percutaneous cholecystostomy tube (PCT) placement. We studied the healthcare utilization and predictors of cholecystectomy and PCT in patients with ACC.The National Database was queried to study all cirrhotics and non-cirrhotics with ACC between 2010-2014 who underwent initial PCT (with or without follow-up cholecystectomy) or cholecystectomy. Cirrhotic patients were divided into compensated and decompensated cirrhosis. Independent predictors and outcomes of initial PCT and failure to undergo subsequent cholecystectomy were studied.Out of 919 189 patients with ACC, 13 283 (1.4%) had cirrhosis. Among cirrhotics, cholecystectomy was performed in 12 790 (96.3%) and PCT in the remaining 493 (3.7%). PCT was more frequent in cirrhotics (3.7%) than in non-cirrhotics (1.4%). Multivariate analyses showed increased early readmissions [odds ratio (OR) = 2.12, 95% confidence interval (CI): 1.43-3.13, P 0.001], length of stay (effect ratio = 1.39, 95% CI: 1.20-1.61, P 0.001), calendar-year hospital cost (effect ratio = 1.34, 95% CI: 1.28-1.39, P 0.001) and calendar-year mortality (hazard ratio = 1.89, 95% CI: 1.07-3.29, P = 0.030) in cirrhotics undergoing initial PCT compared to cholecystectomy. Decompensated cirrhosis (OR = 2.25, 95% CI: 1.67-3.03, P 0.001) had the highest odds of getting initial PCT. Cirrhosis, regardless of compensated (OR = 0.56, 95% CI: 0.34-0.90, P = 0.020) or decompensated (OR = 0.28, 95% CI: 0.14-0.59, P 0.001), reduced the chances of getting a subsequent cholecystectomy.Cirrhotic patients undergo fewer cholecystectomy incurring initial PCT instead. Moreover, the rates of follow-up cholecystectomy are lower in cirrhotics. Increased healthcare utilization is seen with initial PCT amongst cirrhotic patients. This situation reflects suboptimal management of ACC in cirrhotics and a call for action.

OBJECTIVES: Strong evidence links obesity to esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), and pancreatic cancer (PC). However, national-level studies testing the link between obesity and recent temporal trends in the incidence of these cancers are lacking. METHODS: We queried the Surveillance, Epidemiology, and End Results (SEER) to identify the incidence of EC, GC, CRC, and PC. Cancer surgeries stratified by obesity (body mass index ≥30 kg/m2) were obtained from the National Inpatient Sample (NIS). We quantified trends in cancer incidence and resections in 2002–2013, across age groups, using the average annual percent change (AAPC). RESULTS: The incidence of CRC and GC increased in the 20–49 year age group (AAPC +1.5% and +0.7%, respectively, P < 0.001) and across all ages for PC. Conversely, the incidence of CRC and GC decreased in patients 50 years or older and all adults for EC. According to the NIS, the number of patients with obesity undergoing CRC resections increased in all ages (highest AAPC was +15.3% in the 18–49 year age group with rectal cancer, P = 0.047). This trend was opposite to a general decrease in nonobese patients undergoing CRC resections. Furthermore, EC, GC, and PC resections only increased in adults 50 years or older with obesity. DISCUSSION: Despite a temporal rise in young-onset CRC, GC, and PC, we only identify a corresponding increase in young adults with obesity undergoing CRC resections. These data support a hypothesis that the early onset of obesity may be shifting the risk of CRC to a younger age.

Background Most cytologically indeterminate thyroid nodules (ITNs) with benign molecular testing are not surgically removed. The data on clinical outcomes of these nodules are limited. Methods We retrospectively analyzed all ITNs where molecular testing was performed either with the Afirma gene expression classifier or Afirma gene sequencing classifier between 2011 and 2018 at a single institution. Results Thirty-eight out of 289 molecularly benign ITNs were ultimately resected. The most common reason for surgery was compressive symptoms (39%). In multivariable modeling, patients aged Conclusions Younger age, larger nodule size, presence of an Afirma suspicious nodule other than the index nodule, and compressive symptoms were associated with a higher rate of surgery. The FNR of benign Afirma was significantly higher in nodules with high-risk sonographic features.

Study Objectives Delivery prior to full term affects 37% of US births, including ~400,000 preterm births (1,000,000 early term births (37–38 weeks). Approximately 70% of cases of shortened gestation are spontaneous—without medically-indicated cause. Elucidation of modifiable behavioral factors would have considerable clinical impact. Methods This study examined the role of depressive symptoms and sleep quality in predicting the odds of spontaneous shortened gestation among 317 women (135 black, 182 white) who completed psychosocial assessment in mid-pregnancy. Results Adjusting for key covariates, black women had 1.89 times higher odds of spontaneous shortened gestation compared to White women (OR [95% CI] = 1.89 [1.01, 3.53], p = 0.046). Women who reported only poor subjective sleep quality (PSQI > 6) or only elevated depressive symptoms (CES-D ≥ 16) exhibited no statistically significant differences in odds of spontaneous shortened gestation compared to those with neither risk factor. However, women with comorbid poor sleep and depressive symptoms exhibited markedly higher odds of spontaneous shortened gestation than those with neither risk factor (39.2% versus 15.7% [OR (95% CI) = 2.69 (1.27, 5.70)], p = 0.01). A higher proportion of black women met criteria for both risk factors (23% of black women versus 11% of white women; p = 0.004), with a lower proportion experiencing neither risk factor (40.7% of black versus 64.3% of white women; p < 0.001). Conclusions Additive effects of poor subjective sleep quality and depressive symptoms were observed with markedly higher odds of spontaneous shortened gestation among women with both risk factors. Racial inequities in rates of comorbid exposure corresponded with inequities in shortened gestation. Future empirical studies and intervention efforts should consider the interactive effects of these commonly co-morbid exposures.

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.

Introduction Low-molecular-weight heparins are the standard treatment for cancer-associated thrombosis. Recently, direct oral anticoagulants are a new option for thrombosis treatment; however, data supporting the use of direct oral anticoagulants for cancer-associated thrombosis are limited. Objectives The primary objective of this study was to determine the rate of recurrent cancer-associated thrombosis and major bleeding within 6 months of starting either low-molecular-weight heparin or direct oral anticoagulant for treatment of cancer-associated thrombosis. Secondary objectives were to determine the rates of clinically relevant-non-major bleeding and all-cause mortality. Patients/methods This is a retrospective cohort study including adults with cancer-associated thrombosis treated with low-molecular-weight heparin or direct oral anticoagulant between 2010 and 2016 at the Ohio State University. Medical records were reviewed for 6 months after initiation of anticoagulation or until the occurrence of recurrent cancer-associated thrombosis, major bleeding, cessation of anticoagulation of interest, or death, whichever occurred first. Results Four hundred and eighty patients were included (290 low-molecular-weight heparin and 190 direct oral anticoagulant). Patients treated with direct oral anticoagulant were found to carry “lower risk” features including cancer with lower VTE risk and lower rate of metastatic disease. After adjustment for baseline differences, there was no significant difference in the rate of recurrent cancer-associated thrombosis (7.2% low-molecular-weight heparin vs 6.3% direct oral anticoagulant, p = 0.71) or major bleeding (7.6% low-molecular-weight heparin vs 2.6% direct oral anticoagulant, p = 0.08). Conclusions Our study demonstrates that in a select population of cancer patients with VTE, direct oral anticoagulant use can be as effective and safe compared to the standard therapy with low-molecular-weight heparin.

INTRODUCTION Contrast induced nephropathy is linked to contrast utilization and strategies for minimizing renal injury are incorporated into many laboratories that perform coronary angiography. Contrast limits have been described, below which there is minimal incremental increase in the risk of renal injury. Whether a priori acknowledgement of these limits as part of a contrast "Time-Out" reduces contrast utilization has not been established. In this study, we investigate the effect of verbalizing pre-angiography and ½ time contrast thresholds on contrast utilization and associated clinical outcomes. METHODS We retrospectively reviewed 5265 cases of coronary angiography (984 with contrast thresholds defined pre-procedure compared to 4281 without pre-defined contrast thresholds). There were two primary endpoints: (1) proportion of procedures that utilized an amount of contrast ≤ threshold, and (2) median difference between amount of contrast utilized and the contrast threshold. Secondary outcomes incorporated indices of renal function, and included changes in serum creatinine levels, eGFR, and CKD stage. RESULTS Compared to pre-"Time-Out" group, the post-"Time-Out" group had a higher proportion of procedures with contrast ≤ stated contrast threshold (88% vs 84%, P

BACKGROUND Obstructive sleep apnea (OSA) is associated with vascular endothelial dysfunction (VED) in otherwise healthy patients. The role of renin–angiotensin system (RAS) in the OSA induced VED is not well understood. METHODS Recently diagnosed OSA patients with very low cardiovascular disease (CVD) risk (Framingham score RESULTS In OSA patients (n = 11), microcirculatory endothelial AT1 expression decreased from 873 (200) (fluorescence units) at baseline to 393 (59) units after 12 weeks of CPAP (P = 0.02). AT2 expression did not decrease significantly in these patients (479 (75) to 329 (58) post CPAP (P = 0.08)). The ex-vivo addition of the losartan to the microcirculatory endothelium resulted in decreased superoxide expression in the vascular walls from 14.2 (2.2) units to 4.2 (0.8) P < 0.001; while it had no effect on post-CPAP patient tissue (P = 0.64). CONCLUSIONS In OSA patients with no to minimal CVD risk, VED is associated with upregulation of AT-1 expression that is reversible with CPAP. Endothelial oxidative stress was reversible with ARB. RAS activation may play an important role in the development of early CVD risk in OSA patients.

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).

Little has been reported about how to improve health care access and delivery for adolescents and adults with autism spectrum disorder. To understand the contributions to the health disparities in the autism spectrum disorder population, we conducted two independent research approaches to learn about current medical needs. A retrospective chart review was performed to evaluate medical comorbidities and medication use. A focus group was also created to address barriers faced in providing medical care. Of 126 charts reviewed, 49% (n = 62) had intellectual disability, 49% (n = 62) had attention-deficit hyperactivity disorder, 52% (n = 65) had anxiety, 41% (n = 52) had obesity, 31% (n = 39) with a history of aggressive behavior, 31% (n = 31) had depression, 22% (n = 28) had seizures, and 9% (n = 11) had hypertension. A Medical Regimen Complexity Index score was determined to examine medication use trends in the autism spectrum disorder population. Medical Regimen Complexity Index scores were significantly higher for patients with intellectual disability, patients with seizures, and patients with a history of aggressive behavior. Both the focus group and our pre-visit assessment identified the waiting room and waiting time as barriers to care. Understanding the comorbidities, polypharmacy, and medical barriers should provide a better understanding of the current health care access and delivery needs of adolescents and adults with autism spectrum disorder.

OBJECTIVE: Post-operative thyroglobulin (Tg) levels can predict the likelihood of residual cancer, including distant metastases, thereby influencing postsurgical treatment strategies even in patients with low-risk disease. Circulating anti-thyroglobulin antibodies (anti-Tg Abs) interfere with Tg measurement preventing this clinical use. It is not known if the presence of anti-Tg Abs predicts metastatic disease on post-therapy scan in patients with low-risk disease or if they should influence the use or dose of I-131 therapy. In the present study, we compare post-therapy scans in low-risk patients with and without anti-Tg Abs. METHODS: This is a single-institution retrospective study. The study population (Group A) included all patients with low-risk differentiated thyroid cancer (DTC) who underwent total thyroidectomy and RAI between 1/1/2006 to 9/11/2015 with intrathyroidal T1–T2, Nx, N0 or N1a (≤5 nodes all measuring, when reported

Background and purpose To assess impact of a pharmacist-led educational intervention on family nurse practitioner (FNP) students’ prescribing skills, perception of preparedness to prescribe, and perception of pharmacist as collaborator. Method Prospective pre–post assessment of a 14-week educational intervention in an FNP program in the spring semester of 2014. Students participated in an online module of weekly patient cases and prescriptions emphasizing legal requirements, prescription accuracy, and appropriate therapy. A pharmacist facilitator provided formative feedback on students’ submissions. Participants completed a matched assessment on prescription writing before and after the module, and a retrospective postsurvey then presurvey to collect perceptions. Conclusion There was significant improvement in performance on error identification and demonstration of prescription elements from preassessment to postassessment (+17%, p < .001). The mean performance on both assessments was less than the 70% passing score. Students reported significant positive changes in perceptions, including all statements regarding their preparedness to prescribe and those addressing willingness to collaborate with pharmacists. Implications for practice Formative education on prescribing enhanced students’ understanding of safe and effective medication use with improved recognition and avoidance of prescribing errors, although it did not result in competency. Exposure to pharmacist expertise in this area may encourage collaboration in practice.

Thyroglobulin (Tg) measurement in patients with positive antithyroglobulin antibodies (anti-TgAbs) is not reliable. Tg measurement using liquid chromatography-tandem mass spectrometry (LC/MS) may be useful in this setting.This is a retrospective study with the objective of determining the accuracy of Tg-LC/MS in patients with thyroid cancer with anti-TgAbs. All patients with follicular cell-derived thyroid cancer (TC) who had thyroglobulin measured using LC/MS assay from November 1, 2013, to November 7, 2014, were evaluated. The frequency of detectable Tg-LC/MS was evaluated, with a functional sensitivity (FS) of 0.5 ng/mL in patients with structural disease. Then performance of Tg-LC/MS versus Tg immunometric assay (IMA) was compared using either Immulite assay (Tg-1) with a FS of 0.9 ng/mL or Beckman assay (Tg-B) with a FS of 0.1 ng/mL in detecting structural disease in patients with positive anti-TgAbs.A total of 154 consecutive patients were included in this evaluation. Of these, 116 (75%) patients were positive for anti-TgAbs. In patients with structural disease and positive anti-TgAbs, Tg-LC/MS was undetectable in 43.7% of patients. Then the diagnostic accuracy for structural disease of Tg-LC/MS was compared with each Tg-IMA assay separately. In the 26 patients with positive anti-TgAbs where a Tg-I assay was used, the sensitivity and specificity for detecting structural disease were 33.3% and 88.2%, respectively, for the Tg-I assay, and 44.4% and 94.1%, respectively, for the Tg-LC/MS assay. In the 74 patients with positive anti-TgAbs where Tg-B was used, the sensitivity and specificity for detection of structural disease were 72.7% and 71.4%, respectively, for the Tg-B assay, and 62.6% and 93.7%, respectively, for the Tg-LC/MS assay.In patients with thyroid cancer with positive anti-TgAbs, Tg-LC/MS was frequently undetectable and was less sensitive for detecting disease than a Tg assay was with a functional sensitivity of 0.1 ng/mL. For patients with detectable Tg-LC/MS and anti-TgAbs, use of the assay for monitoring requires further prospective studies.

Reduction of early hospital readmissions is a declared goal in the United States economic and quality improvement agenda. A retrospective study was performed using the Nationwide Readmissions Database from 2010 to 2014. Our primary aim was to study the rate of early readmissions and its predictors in liver transplant recipients (LTRs). Our secondary aims were to determine the trends of LT, reasons for readmission, costs and predictors of calendar year mortality. Multivariable logistic regression and Cox proportional hazards models were utilized. The 30-day readmission rate was 30.6% among a total of 25,054 LTRs. Trends of LT were observed to be increased in patients > 65 years (11.7–17.8%, p p = 0.001) during study period. The majority of 30-day readmissions were due to post transplant complications, with packed red blood cell transfusions being the most common intervention during readmission. Medicaid or Medicare insurance, surgery at low and medium volume centers, infections, hemodialysis, liver biopsy, and length of stay > 10 days were the predictors of 30-day readmission. Moreover, number of early readmission, age > 64 years, non-alcoholic cirrhosis, and length of stay > 10 days were significant predictor of calendar year mortality in LTRs. Approximately one third of patients require early admission after LT. Early readmission not only increases burden on healthcare, but is also associated with calendar year mortality. Strategies should be implemented to reduce readmission in patients with high risk of readmission identified in our study.

Evidence guiding inpatient management of buprenorphine is lacking-this retrospective cohort study evaluated the clinical impact of hospital continuation versus discontinuation of buprenorphine at an academic medical center. The primary outcome was inpatient oral morphine equivalents (OME). Secondary outcomes included patient pain levels, functional assessment, and hospital length of stay. One hundred thirty-one patients (74 continued buprenorphine, 57 discontinued) were included in the analysis. Median OME were significantly lower among patients continued on buprenorphine versus discontinued (11 mg vs 103 mg

The majority of pancreatic cancers are diagnosed at an advanced stage, when surgical options are limited and treatment relies on systemic chemotherapy. In the NAPOLI-1 trial, liposomal irinotecan in combination with fluorouracil (nal-iri/5FU) was shown to improve overall survival when compared to fluorouracil alone for metastatic pancreatic cancer. Other retrospective studies have shown the combination of fluorouracil and conventional irinotecan (FOLFIRI) to be a viable option, though no randomized trials have compared nal-iri/5FU to FOLFIRI. The purpose of this single-center, retrospective, cohort study was to determine if nal-iri/5FU and FOLFIRI are similarly effective for the treatment of advanced pancreatic cancer. Due to the potential for treatment bias, inverse probability of treatment weighting was utilized to correct for baseline differences between the groups. The primary outcome of progression-free survival was similar at 4.1 months for nal-iri/5FU and 3.1 months for FOLFIRI. Overall survival and adverse effect frequency were also similar. Pegfilgrastim was used in 16% and 15% of patients, respectively, and nal-iri/5FU patients required significantly less atropine during treatment (36 vs. 70%). A cost analysis was conducted and concluded that the treatment with nal-iri/5FU was nearly 30 times more expensive than FOLFIRI treatment. Together, these data suggest a potential role for FOLFIRI for the treatment of advanced pancreatic cancer in the absence of clear benefits in effectiveness, toxicity, or cost for nal-iri/5FU.

Background and Aims Previous studies have validated EUS-guided needle-based confocal laser endomicroscopy (nCLE) diagnosis of intraductal papillary mucinous neoplasms (IPMNs). We sought to derive EUS-guided nCLE criteria for differentiating IPMNs with high-grade dysplasia/adenocarcinoma (HGD-Ca) from those with low/intermediate-grade dysplasia (LGD). Methods We performed a post hoc analysis of consecutive IPMNs with a definitive diagnosis from a prospective study evaluating EUS-guided nCLE in the diagnosis of pancreatic cysts. Three internal endosonographers reviewed all nCLE videos for the patients and identified potential discriminatory EUS-guided nCLE variables to differentiate HGD-Ca from LGD IPMNs (phase 1). Next, an interobserver agreement (IOA) analysis of variables from phase 1 was performed among 6 blinded external nCLE experts (phase 2). Last, 7 blinded nCLE-naive observers underwent training and quantified variables with the highest IOA from phase 2 using dedicated software (phase 3). Results Among 26 IPMNs (HGD-Ca in 16), the reference standard was surgical histopathology in 24 and cytology confirmation of metastatic liver lesions in 2 patients. EUS-guided nCLE characteristics of increased papillary epithelial “width” and “darkness” were the most sensitive variables (90%; 95% confidence interval [CI], 84%-94% and 91%; 95% CI, 85%-95%, respectively) and accurate (85%; 95% CI, 78%-90% and 84%; 95% CI, 77%-89%, respectively) with substantial (κ = 0.61; 95% CI, 0.51-0.71) and moderate (κ = 0.55; 95% CI, 0.45-0.65) IOAs for detecting HGD-Ca, respectively (phase 2). Logistic regression models were fit for the outcome of HGD-Ca as predictor variables (phase 3). For papillary width (cut-off ≥50 μm), the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for detection of HGD-Ca were 87.5% (95% CI, 62%-99%), 100% (95% CI, 69%-100%), and 0.95, respectively. For papillary darkness (cut-off ≤90 pixel intensity), the sensitivity, specificity, and AUC for detection of HGD-Ca were 87.5% (95% CI, 62%-99%), 100% (95% CI, 69%-100%), and 0.90, respectively. Conclusions In this derivation study, quantification of papillary epithelial width and darkness identified HGD-Ca in IPMNs with high accuracy. These quantifiable variables can be used in multicenter studies for risk stratification of IPMNs. (Clinical trial registration number: NCT02516488.)

Importance Strategies to activate and engage patients and caregivers in shared decision making in the acute care setting may result in improved outcomes. Objective To determine whether a patient activation tool (PAT) can improve decision-making and patient-centered outcomes among pediatric patients and their caregivers who choose between surgery and nonoperative management for their child’s appendicitis. Design, Setting, and Participants This single-blind, randomized clinical trial collected data from a single tertiary children’s hospital from March 1, 2014, through April 30, 2016, with 1-year follow-up completed on May 1, 2017. Two hundred of 236 eligible children and adolescents aged 7 to 17 years with uncomplicated appendicitis enrolled with their caregivers. After receiving the randomized clinical intervention, caregivers chose surgery or nonoperative management. Data were analyzed from March 1, 2014, through May 1, 2017. Interventions Randomization to a scripted standardized surgical consultation that emphasized patient choice or a scripted standardized surgical consultation plus the PAT (a tablet-based tool that presents each treatment, encourages participation in medical decision making, and aims at alleviating decisional uncertainty). Main Outcomes and Measures Decisional self-efficacy immediately after treatment decision, health care satisfaction at discharge, and disability days for the child at 1-year follow-up. Results Among 200 participants (median age, 12 years [interquartile range (IQR), 9-15 years]; 120 [60.0%] male), 98 were randomized to the PAT and 102 to the standardized consultation groups. The percentages choosing nonoperative management were similar (standardized consultation group, 42 of 102 [41.2%]; PAT group, 31 of 98 [31.6%];P = .19). Immediate decisional self-efficacy was similar in the standardized consultation and PAT groups (median score, 100 [IQR, 97.7-100] vs 100 [IQR, 95.5-100];P = .03), which was not significant at the planned significance level ofP = .02. Total scores on health care satisfaction at discharge were similar (median, 99 [IQR, 94.7-100] vs 98 [IQR, 91.7-100];P = .27). Disability days at 1-year follow-up were also similar (median, 6 [IQR, 2-11] vs 5 [IQR, 2-15];P = .67). No difference in the failure rate of nonoperative management at 1 year (13 of 38 [34.2%] vs 11 of 30 [36.7%];P > .99) or in the rate of complicated appendicitis 30 days after discharge (7 of 68 [10.3%] vs 9 of 71 [12.7%];P = .79) occurred. Conclusions and Relevance In this study, a technology-based PAT did not improve measures of decision making for pediatric patients and caregivers needing to make an urgent treatment decision between surgery and nonoperative management for appendicitis. However, the overall high scores in both groups suggest that pediatric patients and caregivers can process information in the acute care setting and effectively participate in an informed shared decision-making process around the need for surgery. Trial Registration ClinicalTrials.gov identifier:NCT02110485

Obesity is a known risk factor for diverticulitis. Our objective was to examine the less investigated impact of morbid obesity (MO) on admissions and clinical course of diverticulitis in a US representative database.We retrospectively queried the 2010-2014 Nationwide Readmission Database to compare diverticulitis hospitalizations in 48,651 MO and 841,381 non-obese patients. Outcomes of mortality, clinical course, surgical events, and readmissions were compared using multivariable and propensity-score-matched analyses.The number of MO patients admitted with diverticulitis increased annually from 7570 in 2010 to 11,935 in 2014, while the total number of patients admitted with diverticulitis decreased (p = 0.003). Multivariable analysis demonstrates that MO was associated with increased mortality (adjusted odds ratio [aOR] 1.54; 95% confidence internal [CI]: 1.16, 2.05), intensive care admissions (aOR = 1.92; 95% CI: 1.61, 2.31), emergent surgery (aOR = 1.20; 95% CI: 1.11, 1.30), colectomy (aOR = 1.13; 95% CI: 1.08, 1.18), open laparotomy (aOR = 1.28; 95% CI: 1.21, 1.34), and colostomy (aOR = 1.34; 95% CI: 1.25, 1.43). Additionally, MO was associated with higher risk for multiple readmissions for diverticulitis within 30 days (aOR = 1.45; 95% CI: 1.08, 1.96) and 6 months (aOR = 1.21; 95% CI: 1.03, 1.42). A one-to-one matched propensity-score analysis confirmed our multivariable analysis findings.Analysis of national data demonstrates an increasing trend of MO patients' admissions for diverticulitis, with a presentation at a younger age. Furthermore, MO is associated with an increased risk of adverse outcomes and readmissions of diverticulitis. Future strategies are needed to ameliorate these outcomes.

Introduction: Emergence of multidrug-resistant (MDR) gram-negative (GN) pathogens and lack of novel antibiotics have increased the use of colistin, despite unknown optimal dosing. This study aimed to evaluate the safety and efficacy of a colistin loading dose, high-dose (LDHD) maintenance regimen in patients with MDR-GN pneumonia. Methods: A retrospective cohort analysis was performed comparing critically ill patients with MDR-GN pneumonia pre- and postimplementation of a colistin LDHD guideline with a primary outcome of clinical cure. Safety was assessed using incidence of acute kidney injury (AKI) based on RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria. Results: Seventy-two patients met the inclusion criteria (42 preimplementation and 30 postimplementation). Clinical cure was achieved in 23 (55%) patients in the preimplementation group and 20 (67%) patients in the postimplementation group ( P = .31). AKI occurred in 50% of the patients during the preimplementation period and 58% during the postimplementation period ( P = .59) with no difference in initiation rates of renal replacement therapy. Conclusion: The increased clinical cure rate after implementation of the colistin LDHD guideline did not reach statistical significance. The LDHD guideline, however, was not associated with an increased incidence of AKI, despite higher intravenous colistin doses. Opportunity exists to optimize colistin dosage while balancing toxicity, but larger studies are warranted.

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 Adults with autism spectrum disorder (ASD) frequently experience polypharmacy. However, there is limited understanding of how to quantify medication complexity in this vulnerable population. OBJECTIVES This study examined medication administration difficulty using the Medication Regimen Complexity Index (MRCI) tool in adolescents and adults with ASD. The outcomes compared the mean total MRCI score with the medication count, described MRCI contributions for over-the-counter medication (OTC), and compared MRCI scores by patient characteristics. METHODS This was a retrospective chart review of patients aged 7-45 years (mean = 20.1) enrolled in a primary care ASD transitions program. Each patient's listed medications were counted and then scored using the validated MRCI tool. RESULTS For the 142 patients studied, mean total MRCI was 14.6 ± 14.6 (range 0-89) and mean medication count was 6.3 ± 5.4 (range 0-38). For patients on 0-4 medications (66 of 142; 46.5%), the mean MRCI was 5.5 ± 4.2, 5-9 medications (50 of 142; 35.2%) the mean MRCI was 15.2 ± 6.8, and 10-38 medications (26 of 142; 18.3%) the mean MRCI was 36.5 ± 18.9 (p

To compare targeted muscle reinnervation (TMR) to "standard treatment" of neuroma excision and burying into muscle for postamputation pain.To date, no intervention is consistently effective for neuroma-related residual limb or phantom limb pain (PLP). TMR is a nerve transfer procedure developed for prosthesis control, incidentally found to improve postamputation pain.A prospective, randomized clinical trial was conducted. 28 amputees with chronic pain were assigned to standard treatment or TMR. Primary outcome was change between pre- and postoperative numerical rating scale (NRS, 0-10) pain scores for residual limb pain and PLP at 1 year. Secondary outcomes included NRS for all patients at final follow-up, PROMIS pain scales, neuroma size, and patient function.In intention-to-treat analysis, changes in PLP scores at 1 year were 3.2 versus -0.2 (difference 3.4, adjusted confidence interval (aCI) -0.1 to 6.9, adjusted P = 0.06) for TMR and standard treatment, respectively. Changes in residual limb pain scores were 2.9 versus 0.9 (difference 1.9, aCI -0.5 to 4.4, P = 0.15). In longitudinal mixed model analysis, difference in change scores for PLP was significantly greater in the TMR group compared with standard treatment [mean (aCI) = 3.5 (0.6, 6.3), P = 0.03]. Reduction in residual limb pain was favorable for TMR (P = 0.10). At longest follow-up, including 3 crossover patients, results favored TMR over standard treatment.In this first surgical RCT for the treatment of postamputation pain in major limb amputees, TMR improved PLP and trended toward improved residual limb pain compared with conventional neurectomy.NCT02205385 at ClinicalTrials.gov.

There are limited data on the role of neck ultrasound (US) in the surveillance of patients with follicular thyroid cancer (FTC). Here, we analyze the likelihood of US to find structural disease in patients with FTC and evaluate if initial American Thyroid Association (ATA) risk stratification and the response to therapy categories [the latter based on thyroglobulin (Tg) levels] modify that likelihood. We conducted a retrospective cohort study of 32 patients with FTC in our institution. We included all patients with well-differentiated FTC who underwent total thyroidectomy and radioactive iodine (RAI) treatment without neck structural disease at the time of RAI and with Tg and US at least 6 months after RAI. After a median follow-up of 4.3 years, two patients (6.3%) had structural disease by US. None of the 18 patients with initial ATA low-risk disease had structural disease by US in contrast to higher, but not significant, frequency of 18.2% (2/11) in patients with initial ATA high-risk disease (p = 0.14). Based on Tg levels, 24/32 patients had excellent response to therapy and 8/32 had biochemical incomplete/indeterminate response. None of the patients with excellent response had structural disease by US versus 2/8 (25%) patients with biochemical incomplete/indeterminate response all of whom had other sites of structural disease (p = 0.054). Our findings suggest that neck US in FTC is unlikely to find structural disease with initial low-risk ATA or excellent response to therapy but can detect structural disease in some patients with initial ATA high-risk or incomplete/indeterminate responses to therapy.

The benefits of oxandrolone in burn patients has led to its accepted use in the burn care community, however details regarding the most common adverse effect, transaminitis, remains unclear. The purpose of this study was to determine the incidence of transaminitis in patients with burn injury and identify risk factors associated with the development of transaminitis. This single-center, retrospective risk factor analysis compared burn patients on oxandrolone with and without the development of transaminitis, defined as any aspartate aminotransferase or alanine aminotransferase value >100mg/dL. Patient demographics, past medical history, lab values, and burn characteristics were recorded. Overall 28 out of 66 (42%) patients developed transaminitis. The transaminitis group had a significantly higher proportion of other concomitant medications with a transaminitis risk (p=0.045). No significant difference in liver dysfunction or length of stay was observed between the two groups. Oxandrolone induced transaminitis is occurring in patients significantly more frequently than previously reported warranting further research to guide monitoring requirements, use of concomitant medications, and to determine if rechallenging after resolution should be considered.

Analgesia and sedation protocols (ASPs) reduce duration of mechanical ventilation (MV) in the medical intensive care unit (ICU), but data in the surgical ICU (SICU) are limited. The objective of this study was to determine the impact of a nursing-driven ASP with criteria for infusion initiation in the SICU.A single-center, retrospective study compared ventilator-free days at day 28 from start of MV (VFD28) before and after ASP implementation. Secondary endpoints included cumulative opioid and sedative requirements, level of sedation, incidence of delirium, SICU and hospital length of stay.One hundred thirty two patients were included (66 per group). The protocol group had greater VFD28 compared to the control group (21 vs. 14.5 days, p = .04). Lower rates of benzodiazepine (42.4% vs. 84.8%, p .001) and opioid (24.2 vs. 78.8, p .001) infusion use occurred in the protocol group, resulting in lower cumulative doses per ventilator-day through day 7. The protocol group had more documented sedation scores within target range. There were no differences in ICU delirium, SICU or hospital length of stay.A nursing-driven ASP with criteria for infusion initiation in mechanically-ventilated SICU patients may increase ventilator-free time, maintain patients at the target sedation goal, and reduce opioid and benzodiazepine utilization.

Introduction: Options for the treatment of the behavioral and psychological symptoms of dementia (BPSD) are limited. Atypical antipsychotics are often used but have questionable efficacy and are generally considered high risk. Therefore, the objective of this study is to evaluate the efficacy and safety of using any atypical antipsychotic for the treatment of BPSD among outpatients. Methods: Retrospective observational study of an academic outpatient memory disorders clinic. Participants included any community-dwelling patient with a diagnosis of dementia, not trauma induced, with documented BPSD treated with an atypical antipsychotic for at least 2 weeks. Medical records were reviewed from January 1, 1990 to March 23, 2010. Safety outcomes were documented from the time of antipsychotic initiation, and behavioral/psychological efficacy outcomes were documented beginning 2 weeks after antipsychotic therapy was initiated, until the last documentation available. Results: A total of 87 distinct antipsychotic treatment periods for 81 unique patients were included. Antipsychotic treatment was continued for more than a year in 33% of patients and only 17% of patients discontinued antipsychotic treatment over the entire period. The behavioral/psychological outcomes improved for 24 (28%) treatments, remained stable for 17 (20%) treatments, and worsened for 46 (53%) treatments. Adverse events were reported by 53% of patients, with the most common adverse events being metabolic, fall related, type, and vascular. Few adverse events were severe. The odds ratio of adverse events per every 90-day increase in duration of treatment was 1.20 ( P = 0.02). Conclusion: Antipsychotic treatment improved behavioral/psychological symptoms for less than one-third of patients and increased the potential risk of adverse events for more than half of patients.

Clostridium difficile infection (CDI) is major health care concern with reports linking it to obesity. Our aim was to investigate the little known impact of the two most common bariatric surgeries, Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), on risk of CDI admissions. This is a retrospective cohort study using the 2013 Nationwide Readmission Database. We examined inpatient CDI rates within 120 days after RYGB (n = 40,059) and VSG (n = 45,394). In a time to event analysis we also evaluated inpatient CDI rates up to 11 months post-surgery. We chose morbidly obese patients that underwent non-emergent ventral hernia repair (VHR) as additional surgical controls (n = 9673). CDI rates were higher after RYGB than VSG in the first 30 days (odds ratio [OR] = 2.10; 95% confidence interval [CI], 1.05–4.20) with a similar but nonsignificant trend within 31–120 days. CDI rates were also higher after RYGB compared to VHR controls within 31–120 days after surgery (OR = 3.22, 95%CI: 1.31, 7.88, p = 0.01). In a time to event analysis with up to 11 months follow up, RYGB led to higher CDI compared to VSG (hazard ratio [HR] = 1.87; 95% CI, 1.12–3.13) with a trend towards higher CDI compared to VHR (HR = 1.95; 95% CI, 0.94–4.06). Similar CDI rates occurred after VSG vs VHR. RYGB may increase the risk of CDI hospitalization when compared to VSG and VHR controls. This data suggest VSG may be a better bariatric choice when post-surgical CDI risk is a concern.

Study objectives Poor sleep promotes inflammation. In turn, inflammation is a causal mechanism in term as well as preterm parturition. In the United States, a persistent racial disparity in preterm birth exists, with African Americans showing ∼1.5 times greater risk. This study examined associations among sleep quality, serum proinflammatory cytokines, and length of gestation in a racially diverse sample of 138 pregnant women. Design Observational. Measurements Women completed the Pittsburgh Sleep Quality Index (PSQI) and other psychosocial and behavioral measures during midpregnancy. Serum levels of interleukin (IL)-6, IL-8, IL-1β, and tumor necrosis factor (TNF)-α were determined by high-sensitivity assays. Birth outcomes were determined via medical record review. Results Among African American women (n = 79), shorter gestation was predicted by poorer overall sleep (rs = -0.35, P = 0.002) as well the following PSQI subscales: subjective sleep quality (rs = -0.34, P = 0.002), sleep latency (rs = -0.27, P = 0.02), and sleep efficiency (rs = -0.27, P = 0.02). African American women with poor sleep quality (PSQI > 5) had 10.2 times the odds of preterm birth compared to those with good sleep quality. In contrast, among European American women (n = 53), gestational length was not significantly predicted by sleep quality (Ps > 0.12). Bootstrapping analyses showed that, among African Americans, IL-8 significantly mediated the association between sleep quality and length of gestation (indirect effect estimate -0.029; 95% confidence interval -0.06, -0.002). Conclusions The data provide novel evidence that African American women exhibit greater inflammation in response to sleep disturbance than European American women and these effects correspond with length of gestation. Racial differences in susceptibility to sleep induced immune dysregulation may contribute to marked racial disparities in preterm birth.

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.

Family history is important for assessing risk of cancer. This study aimed to improve cancer family history communication and collection by training and motivating lay individuals to construct pedigrees. The authors' ultimate goal is to improve identification of familial cancer. Participants (n = 200) completed preintervention, postintervention, and 1-week follow-up surveys to assess pedigree construction. The intervention reviewed basic construction and interpretation of a pedigree for familial cancer. As a result of intervention, individuals reported more positive attitudes about collecting family history, were more likely to intend to speak to family and physicians about cancer risk, better understood a sample pedigree, and constructed more detailed pedigrees of their family history. At follow-up, 25% of the sample had spoken with their families about cancer risk. For those individuals who had not spoken with family, higher postintervention pedigree knowledge was associated with greater intentions to speak with family in the future. The intervention improved the communication and collection of pedigrees and communication about cancer risk, which could be used to improve the identification of individuals with familial cancers and awareness of family cancer risk.

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.