The urachus revisited: multimodal imaging of benign & malignant urachal pathology.

The urachus is a fibrous tube extending from the umbilicus to the anterosuperior bladder dome that usually obliterates at week 12 of gestation, becoming the median umbilical ligament. Urachal pathology occurs when there is incomplete obliteration of this channel during foetal development, resulting in the formation of a urachal cyst, patent urachus, urachal sinus or urachal diverticulum. Patients with persistent urachal remnants may be asymptomatic or present with lower abdominal or urinary tract symptoms and can develop complications. The purpose of this review is to describe imaging features of urachal remnant pathology and potential benign and malignant complications on ultrasound, CT, positron emission tomography CT and MRI.

Health Research Using Facebook to Identify and Recruit Pregnant Women Who Use Electronic Cigarettes: Internet-Based Nonrandomized Pilot Study.

BACKGROUND: Participant recruitment is often a challenge, particularly enrolling individuals with relatively rare characteristics. The wide reach of social media may provide a mechanism to overcome these challenges. OBJECTIVE: This paper aimed to provide information to researchers who seek to recruit participants from rare populations using social media for studies with demanding protocols. We aimed to describe a pilot study protocol that identified and enrolled pregnant women (second or third trimester) who were exclusive users of electronic cigarettes (e-cigarettes). We have described the recruitment methods, time, and cost; examined advertisement types that were more or less successful; discussed participant retention and relationship management; and described the process of collecting biological data. METHODS: In an open-access, nonrandomized pilot study, we placed Facebook advertisements that were selectively targeting women who were likely to be pregnant and interested in e-cigarettes or vaping. The advertisements invited individuals to complete a fully automated eligibility screener based on Qualtrics. Eligible participants were asked to (1) complete a Web-based survey that collected detailed information on the use of e-cigarettes, including the exact type of device and electronic liquid, (2) report the frequency and intensity of e-cigarette use for 3 months before pregnancy and during each trimester, and (3) provide a saliva specimen for a nicotine biomarker assay. We collected a photograph of each participant's e-cigarette device, 8 weeks after the mother's due date, to allow corroboration of the self-report and the baby's birth weight and gestational age from the participant's physician. RESULTS: Participants were recruited between August 19 and October 26, 2017. We enrolled 20 participants in 2 months at a cost of US $3421.28. Baseline data were collected for all 20 participants. Of the 20 women enrolled, 16 provided a saliva sample, 4 provided a photo of the e-cigarette device, and 10 provided physician contact information. Of the 10 physicians contacted by mail, 6 responded with information on the participants and their babies. CONCLUSIONS: Study findings suggest that Facebook's targeting criteria should focus on e-cigarette users to maximize advertisement exposure of potentially eligible women. In addition, saliva sample collection was feasible among pregnant women (second or third trimester) who were exclusive e-cigarette users, but obtaining photographs and physician reports was problematic and called for further refinement. These lessons are likely useful to others who are seeking to use social media to recruit participants from rare populations into studies with demanding protocols.

Supplementing a survey with respondent Twitter data to measure e-cigarette information exposure.

Social media data are increasingly used by researchers to gain insights on individuals' behaviors and opinions. Platforms like Twitter provide access to individuals' postings, networks of friends and followers, and the content to which they are exposed. This article presents the methods and results of an exploratory study to supplement survey data with respondents' Twitter postings, networks of Twitter friends and followers, and information to which they were exposed about e-cigarettes. Twitter use is important to consider in e-cigarette research and other topics influenced by online information sharing and exposure. Further, Twitter metadata provide direct measures of user's friends and followers as opposed to survey self-reports. We find that Twitter metadata provide similar information to survey questions on Twitter network size without inducing recall error or other measurement issues. Using sentiment coding and machine learning methods, we find Twitter can elucidate on topics difficult to measure via surveys such as online expressed opinions and network composition. We present and discuss models predicting whether respondents' tweet positively about e-cigarettes using survey and Twitter data, finding the combined data to provide broader measures than either source alone.

Disappearing portal venous gas in acute pancreatitis and small bowel ischemia.

We report an usual case of hepatic portal venous gas (HPVG) in the setting of acute pancreatitis and small bowel ischemia. Interestingly, the HPVG disappeared within 2 hours of the original computed tomography scan, despite the patient having small bowel ischemia. The patient had a complicated clinical course, dying 62 days postadmission. This case highlights that HPVG in setting of acute pancreatitis and small bowel ischemia has a very high morbidity and mortality, requiring early detection and aggressive surgical management.

Comparing Twitter and Online Panels for Survey Recruitment of E-Cigarette Users and Smokers.

BACKGROUND: E-cigarettes have rapidly increased in popularity in recent years, driven, at least in part, by marketing and word-of-mouth discussion on Twitter. Given the rapid proliferation of e-cigarettes, researchers need timely quantitative data from e-cigarette users and smokers who may see e-cigarettes as a cessation tool. Twitter provides an ideal platform for recruiting e-cigarette users and smokers who use Twitter. Online panels offer a second method of accessing this population, but they have been criticized for recruiting too few young adults, among whom e-cigarette use rates are highest. OBJECTIVE: This study compares effectiveness of recruiting Twitter users who are e-cigarette users and smokers who have never used e-cigarettes via Twitter to online panelists provided by Qualtrics and explores how users recruited differ by demographics, e-cigarette use, and social media use. METHODS: Participants were adults who had ever used e-cigarettes (n=278; male: 57.6%, 160/278; age: mean 34.26, SD 14.16 years) and smokers (n=102; male: 38.2%, 39/102; age: mean 42.80, SD 14.16 years) with public Twitter profiles. Participants were recruited via online panel (n=190) or promoted tweets using keyword targeting for e-cigarette users (n=190). Predictor variables were demographics (age, gender, education, race/ethnicity), e-cigarette use (eg, past 30-day e-cigarette use, e-cigarette puffs per day), social media use behaviors (eg, Twitter use frequency), and days to final survey completion from survey launch for Twitter versus panel. Recruitment method (Twitter, panel) was the dependent variable. RESULTS: Across the total sample, participants were recruited more quickly via Twitter (incidence rate ratio=1.30, P=.02) than panel. Compared with young adult e-cigarette users (age 18-24 years), e-cigarette users aged 25 to 34 years (OR 0.01, 95% CI 0.00-0.60, P=.03) and 35 to 44 years (OR 0.01, 95% CI 0.00-0.51, P=.02) were more likely to be recruited via Twitter than panel. Smokers aged 35 to 44 years were less likely than those aged 18 to 24 years to be recruited via Twitter than panel (35-44: OR 0.03, 95% CI 0.00-0.49, P=.01). E-cigarette users who reported a greater number of e-cigarette puffs per day were more likely to be recruited via Twitter than panel compared to those who reported fewer puffs per day (OR 1.12, 95% CI 1.05-1.20, P=.001). With each one-unit increase in Twitter usage, e-cigarette users were 9.55 times (95% CI 2.28-40.00, P=.002) and smokers were 4.91 times (95% CI 1.90-12.74, P=.001) as likely to be recruited via Twitter than panel. CONCLUSIONS: Twitter ads were more time efficient than an online panel in recruiting e-cigarette users and smokers. In addition, Twitter provided access to younger adults, who were heavier users of e-cigarettes and Twitter. Recruiting via social media and online panel in combination offered access to a more diverse population of participants.

Pharmacokinetics, Pharmacodynamics, and Safety of Single-Dose Rivaroxaban in Chronic Hemodialysis.

BACKGROUND: This study aimed to characterize the single-dose pharmacokinetic (PK) and pharmacodynamic (PD) profile of rivaroxaban 15 mg administered before and after dialysis in subjects with end-stage renal disease (ESRD), and to compare this profile in subjects with ESRD to that in healthy control subjects (creatinine clearance ≥80 ml/min). METHODS: This was an open-label, single-dose, single-center, parallel-group study of rivaroxaban in ESRD subjects who had been clinically stable on maintenance hemodialysis for ≥3 months. In 8 subjects with ESRD, a 15-mg dose of rivaroxaban was administered 2 ± 0.5 h before a hemodialysis session and repeated 7-14 days later at 3 h after a 4-h hemodialysis session. Eight healthy control subjects, matched for age, sex, and body mass index, received one 15-mg rivaroxaban dose. RESULTS: Compared to healthy subjects, area under the rivaroxaban plasma concentration versus time curve (AUC) increased by 56% following post-dialysis administration. Assuming similar bioavailability between groups, this reflects an approximate 35% decrease in overall drug clearance in ESRD subjects. Pre-dialysis dosing resulted in only 5% lowering of AUC versus post-dialysis dosing, confirming the minimal impact of dialysis on the PK of rivaroxaban. PD effects, as assessed by change in prothrombin time, percent factor Xa inhibition, and anti-Xa activity, were generally concordant with observed changes in plasma PK. CONCLUSIONS: Changes in PK and PD parameters in chronic dialysis patients were generally comparable to changes observed previously in patients with moderate-to-severe renal impairment who were not undergoing dialysis, and support use of a 15-mg dose in this patient population.

Effect of CYP3A perpetrators on ibrutinib exposure in healthy participants.

Ibrutinib (PCI-32765), a potent covalent inhibitor of Bruton's tyrosine kinase, has shown efficacy against a variety of B-cell malignancies. Given the prominent role of CYP3A in ibrutinib metabolism, effect of coadministration of CYP3A perpetrators with ibrutinib was evaluated in healthy adults. Ibrutinib (120 mg [Study 1, fasted], 560 mg [studies 2 (fasted), and 3 (nonfasted)]) was given alone and with ketoconazole [Study 1; 400 mg q.d.], rifampin [Study 2; 600 mg q.d.], and grapefruit juice [GFJ, Study 3]. Lower doses of ibrutinib were used together with CYP3A inhibitors [Study 1: 40 mg; Study 3: 140 mg], as safety precaution. Under fasted condition, ketoconazole increased ibrutinib dose-normalized (DN) exposure [DN-AUClast: 24-fold; DN-C max: 29-fold], rifampin decreased ibrutinib exposure [C max: 13-fold; AUClast: 10-fold]. Under nonfasted condition, GFJ caused a moderate increase [DN-C max: 3.5-fold; DN-AUC: 2.2-fold], most likely through inhibition of intestinal CYP3A. Half-life was not affected by CYP perpetrators indicating the interaction was mainly on first-pass extraction. All treatments were well-tolerated.

The effect of food on the pharmacokinetics of oral ibrutinib in healthy participants and patients with chronic lymphocytic leukemia.

PURPOSE: To assess ibrutinib pharmacokinetics under fasted and fed conditions, impact of food-intake timing, and the safety and tolerability. METHODS: Three studies were analyzed. Study 1 was a randomized, open-label, single-dose, four-way crossover study in 44 healthy participants. Study 2 was a randomized, repeat-dose crossover study in 16 patients with previously treated chronic lymphocytic leukemia (CLL). Ibrutinib dose was 420 mg in both studies. Study 3 was an open-label, sequential study to assess the effect of a standard breakfast on ibrutinib 560 mg in eight healthy participants. RESULTS: Administration of single-dose ibrutinib under fasting conditions (study 1) resulted in approximately 60 % of exposure compared with drug intake either 30 min before, 30 min after (fed), or 2 h after a high-fat meal. Similar food effect was observed (study 3) when ibrutinib was given 30 min before meal. In CLL patients (study 2), the C max and AUC under fasting conditions were 43 and 61 %, respectively, relative to fed conditions. When administered once-daily in uncontrolled food-intake conditions (≥30 min before or 2 h after), exposures were slightly (≈30 %) lower than in fed condition. When corrected for repeated dosing, pharmacokinetic parameters in healthy participants and patients were comparable. Ibrutinib was generally well tolerated in all settings studied. CONCLUSIONS: Ibrutinib administered in fasted condition reduces exposure to approximately 60 % as compared with dosing in proximity to food-intake, regardless of timing/type of meal. Because repeated drug intake in fasted condition is unlikely, no food restrictions may be needed to administer ibrutinib.

Absorption, metabolism, and excretion of oral ¹4C radiolabeled ibrutinib: an open-label, phase I, single-dose study in healthy men.

The absorption, metabolism, and excretion of ibrutinib were investigated in healthy men after administration of a single oral dose of 140 mg of ¹4C-labeled ibrutinib. The mean (S.D.) cumulative excretion of radioactivity of the dose was 7.8% (1.4%) in urine and 80.6% (3.1%) in feces with <1% excreted as parent ibrutinib. Only oxidative metabolites and very limited parent compound were detected in feces, and this indicated that ibrutinib was completely absorbed from the gastrointestinal tract. Metabolism occurred via three major pathways (hydroxylation of the phenyl (M35), opening of the piperidine (M25 and M34), and epoxidation of the ethylene on the acryloyl moiety with further hydrolysis to dihydrodiol (PCI-45227, and M37). Additional metabolites were formed by combinations of the primary metabolic pathways or by further metabolism. In blood and plasma, a rapid initial decline in radioactivity was observed along with long terminal elimination half-life for total radioactivity. The maximum concentration (Cmax) and area under the concentration-time curve (AUC) for total radioactivity were higher in plasma compared with blood. The main circulating entities in blood and plasma were M21 (sulfate conjugate of a monooxidized metabolite on phenoxyphenyl), M25, M34, M37 (PCI-45227), and ibrutinib. At Cmax of radioactivity, 12% of total radioactivity was accounted for by covalent binding in human plasma. More than 50% of total plasma radioactivity was attributed to covalently bound material from 8 hours onward; as a result, covalent binding accounted for 38% and 51% of total radioactivity AUC(0-24 h) and AUC(0-72 h), respectively. No effect of CYP2D6 genotype was observed on ibrutinib metabolism. Ibrutinib was well-tolerated by healthy participants.

Effects of rifampin, cyclosporine A, and probenecid on the pharmacokinetic profile of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in healthy participants.

OBJECTIVE: Canagliflozin, a sodium-glucose co-transporter 2 inhibitor, approved for the treatment of type-2 diabetes mellitus (T2DM), is metabolized by uridine diphosphate-glucuronosyltransferases (UGT) 1A9 and UGT2B4, and is a substrate of P-glycoprotein (P-gp). Canagliflozin exposures may be affected by coadministration of drugs that induce (e.g., rifampin for UGT) or inhibit (e.g. probenecid for UGT; cyclosporine A for P-gp) these pathways. The primary objective of these three independent studies (single-center, open-label, fixed-sequence) was to evaluate the effects of rifampin (study 1), probenecid (study 2), and cyclosporine A (study 3) on the pharmacokinetics of canagliflozin in healthy participants. METHODS: Participants received; in study 1: canagliflozin 300 mg (days 1 and 10), rifampin 600 mg (days 4-12); study 2: canagliflozin 300 mg (days 1-17), probenecid 500 mg twice daily (days 15-17); and study 3: canagliflozin 300 mg (days 1-8), cyclosporine A 400 mg (day 8). Pharmacokinetics were assessed at prespecified intervals on days 1 and 10 (study 1); on days 14 and 17 (study 2), and on days 2-8 (study 3). RESULTS: Rifampin decreased the maximum plasma canagliflozin concentration (Cmax) by 28% and its area under the curve (AUC) by 51%. Probenecid increased the Cmax by 13% and the AUC by 21%. Cyclosporine A increased the AUC by 23% but did not affect the Cmax. CONCLUSION: Coadministration of canagliflozin with rifampin, probenecid, and cyclosporine A was well-tolerated. No clinically meaningful interactions were observed for probenecid or cyclosporine A, while rifampin coadministration modestly reduced canagliflozin plasma concentrations and could necessitate an appropriate monitoring of glycemic control.

Methodological considerations in analyzing Twitter data.

Twitter is an online microblogging tool that disseminates more than 400 million messages per day, including vast amounts of health information. Twitter represents an important data source for the cancer prevention and control community. This paper introduces investigators in cancer research to the logistics of Twitter analysis. It explores methodological challenges in extracting and analyzing Twitter data, including characteristics and representativeness of data; data sources, access, and cost; sampling approaches; data management and cleaning; standardizing metrics; and analysis. We briefly describe the key issues and provide examples from the literature and our studies using Twitter data to understand public health issues. For investigators considering Twitter-based cancer research, we recommend assessing whether research questions can be answered appropriately using Twitter, choosing search terms carefully to optimize precision and recall, using respected vendors that can provide access to the full Twitter data stream if possible, standardizing metrics to account for growth in the Twitter population over time, considering crowdsourcing for analysis of Twitter content, and documenting and publishing all methodological decisions to further the evidence base.

Estimating the World Trade Center tower population on September 11, 2001: a capture-recapture approach.

I applied the capture-recapture method to estimate the World Trade Center tower population at the time of the September 11, 2001, terrorist attacks. Available lists helped identify 8965 survivors and 2152 confirmed casualties. The capture-recapture model suggested that an additional 4435 survivors were present, putting the total count of all present at 15,552 (95% confidence interval=15,216, 15,897). An accurate estimate represents the potential number at risk for trauma as a result of direct exposure to the events of the day.

Nonresponse bias in a mail survey of physicians.

With the increased pressure on survey researchers to achieve high response rates, it is critical to explore issues related to nonresponse. In this study, the authors examined the effects of nonresponse bias in a mail survey of physicians (N = 3,400). Because slightly more than one half of the sample did not respond to the survey, there was potential for bias if nonresponders differed significantly from responders with respect to key demographic and practice variables. They analyzed response status and timing of response with respect to five variables: gender, region, specialty, urbanicity, and survey length. The potential consequences of nonresponse bias on the survey estimates were then analyzed. Men were more likely to respond, as were physicians receiving a shorter questionnaire. Repeated follow-up attempts reduced gender response bias because male physicians were more likely to be early responders. Overall, higher response rates were not associated with lower response bias.

Measuring and maximizing coverage in the World Trade Center Health Registry.

The World Trade Center Health Registry (WTCHR) is a database for following people who were exposed to the disaster of 11 September 2001. Hundreds of thousands of people were exposed to the immense cloud of dust and debris, the indoor dust, the fumes from persistent fires, and the mental trauma of the terrorist attacks on the WTC on 9/11. The purpose of the WTCHR is to evaluate the potential short- and long-term physical and mental health effects of the disaster. The definitions of the exposed groups are broad and defined based on an understanding of which groups had the highest exposures to the WTC disaster and its aftermath. The four exposure groups include rescue and recovery workers, residents, students and school staff, and building occupants and passersby in Lower Manhattan. While one goal of the WTCHR was to maximize coverage overall and for each exposure group, another was to ensure equal representation within exposure groups. Because of the multiple sample types pursued, several approaches were required to determine eligibility. Estimates of the number of eligible persons in each of the exposed populations were based on the best available information including Census, entity-specific employment figures, and public and private school enrollment data, among other publicly available sources. To address issues of undercoverage and overcoverage a variety of methods were assessed or applied, including a capture-recapture analyses test of overlapping sample building list sources and automated deduplication of sample records. Estimates of the true eligible population indicate that over 400,000 unique individuals were eligible for the baseline health survey. Interviewer-administered surveys were completed with more than 71,000 persons, resulting in an overall enrollment rate of approximately 17 per cent. Coverage was highest among rescue and recovery workers, followed by residents, students and school staff, and building occupants. Both the accuracy of coverage estimates and the raw number and representativeness of enrollees were maximized by our approach to coverage. In designing a registry which relies on multiple pathways and sources of data to build the sample, it is important to develop a comprehensive approach that considers all sources of error and minimizes bias that may be introduced through the methodology.