Ionic-surfactant-mediated electro-dewetting for digital microfluidics.

The ability to manipulate droplets on a substrate using electric signals1-known as digital microfluidics-is used in optical2,3, biomedical4,5, thermal6 and electronic7 applications and has led to commercially available liquid lenses8 and diagnostics kits9,10. Such electrical actuation is mainly achieved by electrowetting, with droplets attracted towards and spreading on a conductive substrate in response to an applied voltage. To ensure strong and practical actuation, the substrate is covered with a dielectric layer and a hydrophobic topcoat for electrowetting-on-dielectric (EWOD)11-13; this increases the actuation voltage (to about 100 volts) and can compromise reliability owing to dielectric breakdown14, electric charging15 and biofouling16. Here we demonstrate droplet manipulation that uses electrical signals to induce the liquid to dewet, rather than wet, a hydrophilic conductive substrate without the need for added layers. In this electrodewetting mechanism, which is phenomenologically opposite to electrowetting, the liquid-substrate interaction is not controlled directly by electric field but instead by field-induced attachment and detachment of ionic surfactants to the substrate. We show that this actuation mechanism can perform all the basic fluidic operations of digital microfluidics using water on doped silicon wafers in air, with only ±2.5 volts of driving voltage, a few microamperes of current and about 0.015 times the critical micelle concentration of an ionic surfactant. The system can also handle common buffers and organic solvents, promising a simple and reliable microfluidic platform for a broad range of applications.

Risk factors for endometrial cancer in Black women.

PURPOSE: The incidence of endometrial cancer (EC) has been increasing faster among Black women than among other racial/ethnic groups in the United States. Although the mortality rate is nearly twice as high among Black than White women, there is a paucity of literature on risk factors for EC among Black women, particularly regarding menopausal hormone use and severe obesity. METHODS: We pooled questionnaire data on 811 EC cases and 3,124 controls from eight studies with data on self-identified Black women (4 case-control and 4 cohort studies). We analyzed cohort studies as nested case-control studies with up to 4 controls selected per case. We used logistic regression to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We observed a positive association between BMI and EC incidence (Ptrend < 0.0001) The OR comparing BMI ≥ 40 vs. < 25 kg/m2 was 3.92 (95% CI 2.91, 5.27). Abdominal obesity among those with BMI < 30 kg/m2 was not appreciably associated with EC risk (OR 1.21, 95% CI 0.74, 1.99). Associations of reproductive history with EC were similar to those observed in studies of White women. Long-term use of estrogen-only menopausal hormones was associated with an increased risk of EC (≥ 5 years vs. never use: OR 2.08, 95% CI: 1.06, 4.06). CONCLUSIONS: Our results suggest that the associations of established risk factors with EC are similar between Black and White women. Other explanations, such as differences in the prevalence of known risk factors or previously unidentified risk factors likely underlie the recent increases in EC incidence among Black women.

Methane emission, nutrient digestibility, and rumen microbiota in Holstein heifers fed 14 different grass or clover silages as the sole feed.

This experiment investigated the variation in enteric methane production and associated gas exchange parameters, nutrient digestibility, rumen fermentation, and rumen microbiome when a range of silages based on different forage types (grass or clover), and different species within the 2 types, were fed as the sole feed to heifers. Three grass species (perennial ryegrass, festulolium, and tall fescue) and 2 clover species (red clover and white clover) were included. Perennial ryegrass was harvested at 2 maturity stages in the primary growth, white clover was harvested once in the primary growth, and 4 cuts of festulolium and tall fescue and 3 cuts of red clover were harvested during the growing season, giving 14 different silage batches in total. Sixteen Holstein heifers 16 to 21 mo old and 2 to 5 mo in pregnancy were fed the silages ad libitum as the sole feed in an incomplete crossover design. Each silage was fed to 4 heifers, except for the 2 perennial ryegrass silages, which were fed to 8 heifers; in total 64 observations. The CH4 production was measured for 3 d in respiration chambers. Heifers fed clover silages had higher dry matter intake (DMI) compared with heifers fed grass silages, and heifers fed tall fescue silages had the numerically the lowest DMI. Compared with grass silages, feeding clover silages led to higher crude protein digestibility but lower neutral detergent fiber (NDF) digestibility. Rumen pH was higher in heifers fed clover silages compared with those fed grass silages. Based on composition analysis, the rumen microbiota of the heifers clustered clearly according to forage type and species. More specifically, 7 of the 34 dominating rumen bacterial genus-level groups showed higher relative abundances for the clover silages, whereas 7 genus-level groups showed higher abundances for the grass silages. Methane yield was higher for heifers fed grass silages than for those fed clover silages when methane production was related to dry matter and digestible organic matter intake, whereas the opposite was seen when related to NDF digestion. The gross energy lost as methane (CH4 conversion factor, %) reduced from 7.5% to 6.7%, equivalent to an 11% reduction. The present study gives the outlines for choosing the optimal forage type and forage species with respect to nutrient digestibility and enteric methane emission in ruminants.

Increased Fellow Scholarly Publication Rate After Implementation of a Comprehensive Research Curriculum and Milestone-Based Research Timeline for Pediatric Emergency Medicine Fellows.

OBJECTIVE: Pediatric subspecialty fellows are required to complete a scholarly product during training; however, many do not bring the work to publication. To amplify our fellows' publication success, our pediatric emergency medicine fellowship program implemented a comprehensive research curriculum and established a milestone-based research timeline for each component of a project. Our objective was to assess whether these interventions increased the publication rate and enhanced the graduated fellows' perceived ability to perform independent research. METHODS: Our study was conducted at a tertiary children's hospital affiliated with an academic university, enrolling 3 fellows each year in its pediatric emergency medicine program. A comprehensive research curriculum and a milestone-based research timeline were implemented in 2011. We analyzed the publication rate of our graduating fellows before (2004-2011) and after (2012-2016) our intervention. In addition, in 2017 we surveyed our previous fellows who graduated from 2004 to 2016 and analyzed factors favoring manuscript publication and confidence with various research skills. RESULTS: During the study period, 38 trainees completed the fellowship program. Publication rate increased from 26% ± 17% to 87% ± 30 % ( P < 0.05). When scoring the importance of various factors, fellows most valued mentorship (5 ± 0 vs 4.3 ± 1.0, P < 0.05, postintervention vs preintervention) for the completion of the fellowship study and manuscript. Fellows after the intervention reported greater confidence in performing an analysis of variance (89% vs 36%, odds ratio, 6.3; 95% confidence interval, 1.4-150.1). CONCLUSIONS: Implementation of a comprehensive research curriculum and a milestone-based research timeline was associated with an increase in the publication rate within 3 years of graduation of our pediatric emergency medicine fellows. After implementation, fellows reported an increased importance of mentorship and greater confidence in performing an analysis of variance. We provide a comprehensive curriculum and a research timeline that may serve as a model for other fellowship programs.

The association of severe pain experienced in the pediatric intensive care unit and postdischarge health-related quality of life: A retrospective cohort study.

BACKGROUND: Pain may be a modifiable risk factor for lower health-related quality of life after pediatric critical illness. AIM: To evaluate the association between severe pain experienced in the (pediatrc intensive care unit) and postdischarge health-related quality of life. METHODS: This was a retrospective cohort study. Children aged 1 month to 18 years admitted to the pediatric intensive care unit and enrolled in the Seattle Children's Hospital Outcomes Assessment Program were included. Pain was assessed every 2 h by bedside nursing staff using a behavioral pain scale or numeric pain scale. A day of severe pain was defined as a pediatric intensive care unit day with ≥25% of pain scores ≥7/10. Baseline (preadmission) and postdischarge (median 6 weeks) health-related quality of life was assessed by the Pediatric Quality of Life Inventory (PedsQL™) or the Stein Jessop Functional Status II-R (FS II-R, for children with developmental disability). The cohort was stratified by diagnosis category (surgical vs. medical), and associations were measured using linear regression models. RESULTS: Among 546 patients, 11.9% experienced ≥1 day of severe pain. In multivariable linear regression, each day of severe pain was independently associated with a lower postdischarge health-related quality of life score by 3.6 points (95% CI -6.3 to -0.9) adjusted for baseline health-related quality of life score, age, baseline cognitive function, days with multi-organ dysfunction, pediatric intensive care unit length of stay, and decline in overall function. This association was stronger among surgical patients than medical patients with each day of severe pain resulting in a lower postdischarge health-related quality of life score by 5.3 points (95% CI -9.6 to -0.9) versus 2.6 points (95% CI -5.8 to 0.6). Surgical patients had lower postdischarge emotional functioning than physical functioning subdomain scores. CONCLUSIONS: Children who experience severe pain in the pediatric intensive care unit have lower postdischarge health-related quality of life adjusting for baseline health-related quality of life, particularly among children who have undergone surgery. Attention to pain management may be important to improve postdischarge health-related quality of life.

Feeding up to 91% concentrate to Holstein and Jersey dairy cows: Effects on enteric methane emission, rumen fermentation and bacterial community, digestibility, production, and feeding behavior.

Due to climate change, periods of drought might be longer and occur more frequently, which challenges roughage production and requires changed feeding of dairy cattle by increasing the grain content of the diet. This study investigated the effect of diets with concentrate proportions up to 91% of dry matter on dry matter intake (DMI), milk production, enteric methane emission, rumen fermentation, rumen bacterial community structure, nutrient digestibility, and feeding behavior of Holstein and Jersey dairy cows. Twelve Danish Holstein and 12 Danish Jersey cows were fed ad libitum with one of 3 total mixed rations differing in concentrate proportion in a continuous design with staggered approach over 19 to 29 d. Dietary concentrate proportions were 49% (C49), 70% (C70), and 91% (C91) on dry matter basis, and were based on increasing proportions of chopped barley straw, dried beet pulp, barley, NaOH-treated wheat, dried distillers grain, and rapeseed cake at the expense of grass/clover silage, corn silage and soybean meal. Cows were adapted to the diets over a 12- to 19-d period, before rumination activity was measured over 3 d. Subsequently, spot samples of feces were collected for digestibility determination over 2 d, and gas exchange was measured on the last 3 d of the experimental period. Shortly after chamber stay, rumen liquid was collected using an oro-ruminal device. Dry matter intake was higher for Holstein than Jersey. Methane emissions (all expressions) were affected by the interaction between breed and diet. Methane per kilogram of DMI was lowered by 18 and 48% for Holstein fed C70 and C91, respectively, compared with C49, whereas this was 17 and 22% respectively for Jersey. Rumen propionate molar proportion increased more, rumen bacterial community was less diverse, and rumination time and rumination chews relative to DMI reduced less for Holstein than for Jersey cows with increasing concentrate level. In conclusion, Holstein dairy cows responded stronger to increased dietary concentrate level regarding methane mitigation, changes in rumen VFA profile, and effect on the rumen bacterial community structure than Jersey cows, whereas Jersey cows responded stronger with regard to rumination time and rumination chews (per kilogram of DMI and per kilogram of neutral detergent fiber intake) than Holstein cows. Thus, diets high in concentrates are a less effective methane mitigation strategy for Jersey than for Holstein.

Guiding Fellows to Independent Practice: Current Trends in Pediatric Emergency Medicine Fellow Supervision.

BACKGROUND: Recent studies highlight the importance of physician readiness to practice beyond graduate training. The Accreditation Council for Graduate Medical Education mandates that pediatric emergency medicine (PEM) fellows be prepared for independent practice by allowing "progressive responsibility for patient care." Prior unpublished surveys of program directors (PDs) indicate variability in approaches to provide opportunities for more independent practice during fellowship training. OBJECTIVES: The aims of the study were to describe practices within PEM fellowship programs allowing fellows to work without direct supervision and to identify any barriers to independent practice in training. DESIGN/METHODS: An anonymous electronic survey of PEM fellowship PDs was performed. Survey items were developed using an iterative modified Delphi process and pilot tested. Close-ended survey responses and demographic variables were summarized with descriptive statistics. Responses to open-ended survey items were reviewed and categorized by theme. RESULTS: Seventy two of 84 PDs (88%) responded to the survey; however, not all surveys were completed. Of the 68 responses to whether fellows could work without direct supervision (as defined by the Accreditation Council for Graduate Medical Education) during some part of their training, 31 (45.6%) reported that fellows did have this opportunity. In most programs, clinical independence was conditional on specific measures including the number of clinical hours completed, milestone achievement, and approval by the clinical competency committee. Reported barriers to fellow practice without direct oversight included both regulatory and economic constraints. CONCLUSIONS: Current training practices that provide PEM fellows with conditional clinical independence are variable. Future work should aim to determine best practices of entrustment, identify ideal transition points, and mitigate barriers to graduated responsibility.

Laryngeal paralysis secondary to cervical bite injuries in five dogs.

CASE HISTORIES: Medical records of a veterinary hospital in Belgium were reviewed for dogs (n = 5) that presented between 2016 and 2019 with laryngeal paralysis secondary to bite wounds to the cervical region received while fighting with other dogs. The time elapsed between the trauma and presentation was from a few hours up to 5 days. CLINICAL FINDINGS AND TREATMENT: Bilateral laryngeal paralysis was identified in three dogs and unilateral laryngeal paralysis in two dogs via endoscopic assessment of laryngeal function. The primary concomitant lesions included tracheal injury in 3/5 dogs and oesophageal injury in 1/5 dogs. One dog with bilateral laryngeal paralysis was treated medically as no signs of dyspnoea were present. Surgical management was elected in 4/5 dogs based on evaluation of their clinical status and lesions revealed by endoscopic examination of upper gastrointestinal and respiratory tracts. Dogs underwent surgical procedures that were determined to be appropriate for treatment of the lesions identified on clinical examination, diagnostic imaging, and endoscopy. The cervical region was explored through a ventral midline approach in 2/4 cases, to close tracheal perforations. Temporary tracheostomy was performed in 2/4 cases. Procedures to correct brachycephalic airway obstructive syndrome were performed in 2/4 cases. Cricoarytenoid lateralisation was performed in 2/4 dogs. Dogs were hospitalised for 2-10 days and received antimicrobial therapy before surgery and for 2-3 weeks after surgery. Physical examination and respiratory function were normal in 3/5 dogs 4-6 months after discharge. Information regarding outcomes for two cases was obtained from the owners by telephone assessment 1-6 months after surgery. The owner of each dog reported the respiratory function to be excellent. DIAGNOSIS: Uni- or bilateral, transient or permanent laryngeal paralysis with concomitant oesophageal, tracheal, or laryngeal lesions following cervical dog bite injuries diagnosed by endoscopic examination of upper gastrointestinal and respiratory tracts. CLINICAL RELEVANCE: This case series describes the diagnosis and management of dogs with laryngeal paralysis secondary to cervical dog bite injuries. To the authors' knowledge, this is the first published report documenting bilateral laryngeal paralysis secondary to cervical dog bite injuries. Clinicians should be aware of this pathology and the importance of investigating laryngeal function in dogs presenting with cervical bites, particularly those with inspiratory dyspnoea. Upper airway and digestive endoscopy are recommended for complete assessment of cervical traumatic injuries.

Outcomes of ß-Hemolytic Streptococcal Necrotizing Skin and Soft-tissue Infections and the Impact of Clindamycin Resistance.

BACKGROUND: ß-Hemolytic streptococci are frequently implicated in necrotizing soft-tissue infections (NSTIs). Clindamycin administration may improve outcomes in patients with serious streptococcal infections. However, clindamycin resistance is growing worldwide, and resistance patterns in NSTIs and their impact on outcomes are unknown. METHODS: Between 2015 and 2018, patients with NSTI at a quaternary referral center were followed up for the outcomes of death, limb loss, and streptococcal toxic shock syndrome. Surgical wound cultures and resistance data were obtained within 48 hours of admission as part of routine care. Risk ratios for the association between these outcomes and the presence of ß-hemolytic streptococci or clindamycin-resistant ß-hemolytic streptococci were calculated using log-binomial regression, controlling for age, transfer status, and injection drug use-related etiology. RESULTS: Of 445 NSTIs identified, 85% had surgical wound cultures within 48 hours of admission. ß-Hemolytic streptococci grew in 31%, and clindamycin resistance was observed in 31% of cultures. The presence of ß-hemolytic streptococci was associated with greater risk of amputation (risk ratio, 1.80; 95% confidence interval, 1.07-3.01), as was the presence of clindamycin resistance among ß-hemolytic streptococci infections (1.86; 1.10-3.16). CONCLUSIONS: ß-Hemolytic streptococci are highly prevalent in NSTIs, and in our population clindamycin resistance was more common than previously described. Greater risk of limb loss among patients with ß-hemolytic streptococci-particularly clindamycin-resistant strains-may portend a more locally aggressive disease process or may represent preexisting patient characteristics that predispose to both infection and limb loss. Regardless, these findings may inform antibiotic selection and surgical management to maximize the potential for limb salvage.

Occurrence and Timing of Subsequent Severe Acute Respiratory Syndrome Coronavirus 2 Reverse-transcription Polymerase Chain Reaction Positivity Among Initially Negative Patients.

Using data for 20 912 patients from 2 large academic health systems, we analyzed the frequency of severe acute respiratory syndrome coronavirus 2 reverse-transcription polymerase chain reaction test discordance among individuals initially testing negative by nasopharyngeal swab who were retested on clinical grounds within 7 days. The frequency of subsequent positivity within this window was 3.5% and was similar across institutions.

Screening is associated with a lower risk of hepatocellular carcinoma-related mortality in patients with chronic hepatitis B.

BACKGROUND & AIMS: Patients with chronic hepatitis B (CHB) infection routinely undergo screening for hepatocellular carcinoma (HCC), but the efficacy of screening remains unclear. We aimed to evaluate the impact of screening with ultrasound and/or serum alpha-fetoprotein (AFP) on HCC-related mortality in patients with CHB. METHODS: We performed a matched case-control study of patients with CHB receiving care through the Veterans Affairs (VA) health administration. Cases were patients who died of HCC between 01/01/2004 and 12/31/2017, while controls were patients with CHB who did not die of HCC. Cases were matched to controls by CHB diagnosis date, age, sex, race/ethnicity, cirrhosis, antiviral therapy exposure, hepatitis B e antigen status, and viral load. We identified screening ultrasound and AFPs obtained in the 4 years preceding HCC diagnosis in cases and the equivalent index date in controls. Using conditional logistic regression, we compared cases and controls with respect to receipt of screening. A lower likelihood of screening in cases corresponds to an association between screening and reduced risk of HCC-related mortality. RESULTS: We identified 169 cases, matched to 169 controls. Fewer cases than controls underwent screening with either screening modality (33.7% vs. 58.6%) or both modalities (19.5% vs. 34.4%). In multivariable conditional logistic regression, screening with either modality was associated with a lower risk of HCC-related mortality (adjusted odds ratio [aOR] 0.21, 95% CI 0.09-0.50), as was screening with both modalities (aOR of 0.13; 95% CI 0.04-0.43). CONCLUSIONS: HCC screening was associated with a substantial reduction in HCC-related mortality in VA patients with CHB. LAY SUMMARY: Patients with hepatitis B infection have a high risk of developing liver cancer. It is therefore recommended that they undergo frequent screening for liver cancer, but whether this leads to a lower risk of dying from liver cancer is not clear. In this study, we show that liver cancer screening is associated with a reduction in the mortality from liver cancer in patients with hepatitis B infection.

Association Between Kidney Clearance of Secretory Solutes and Cardiovascular Events: The Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: The clearance of protein-bound solutes by the proximal tubules is an innate kidney mechanism for removing putative uremic toxins that could exert cardiovascular toxicity in humans. However, potential associations between impaired kidney clearances of secretory solutes and cardiovascular events among patients with chronic kidney disease (CKD) remains uncertain. STUDY DESIGN: A multicenter, prospective, cohort study. SETTING & PARTICIPANTS: We evaluated 3,407 participants from the Chronic Renal Insufficiency Cohort (CRIC) study. EXPOSURES: Baseline kidney clearances of 8 secretory solutes. We measured concentrations of secretory solutes in plasma and paired 24-hour urine specimens using liquid chromatography-tandem mass spectrometry (LC-MS/MS). OUTCOMES: Incident heart failure, myocardial infarction, and stroke events. ANALYTICAL APPROACH: We used Cox regression to evaluate associations of baseline secretory solute clearances with incident study outcomes adjusting for estimated GFR (eGFR) and other confounders. RESULTS: Participants had a mean age of 56 years; 45% were women; 41% were Black; and the median estimated glomerular filtration rate (eGFR) was 43 mL/min/1.73 m2. Lower 24-hour kidney clearance of secretory solutes were associated with incident heart failure and myocardial infarction but not incident stroke over long-term follow-up after controlling for demographics and traditional risk factors. However, these associations were attenuated and not statistically significant after adjustment for eGFR. LIMITATIONS: Exclusion of patients with severely reduced eGFR at baseline; measurement variability in secretory solutes clearances. CONCLUSIONS: In a national cohort study of CKD, no clinically or statistically relevant associations were observed between the kidney clearances of endogenous secretory solutes and incident heart failure, myocardial infarction, or stroke after adjustment for eGFR. These findings suggest that tubular secretory clearance provides little additional information about the development of cardiovascular disease events beyond glomerular measures of GFR and albuminuria among patients with mild-to-moderate CKD.

Association of Antidepressant Continuation in Pregnancy and Infant Birth Weight.

PURPOSE: The aim of the study was to evaluate the association of antidepressant continuation in pregnancy with infant birth weight among women using antidepressants before pregnancy. METHODS: This retrospective cohort study used electronic health data linked with state birth records. We identified singleton live births (2001-2014) to enrolled women with 1 or more antidepressant prescriptions filled 6 months or less before pregnancy, including "continuers" (≥1 antidepressant fills during pregnancy, n = 1775) and "discontinuers" (no fill during pregnancy, n = 1249). We compared birth weight, small or large for gestational age (SGA or LGA), low birth weight (LBW; <2500 g), and macrosomia (>4500 g) between the 2 groups, using inverse probability of treatment weighting to account for pre-pregnancy characteristics, including mental health conditions. RESULTS: After weighting, infants born to antidepressant continuers weighed 71.9 g less than discontinuers' infants (95% confidence interval [CI], -115.5 to -28.3 g), with a larger difference for female infants (-106.4 g; 95% CI, -164.6 to -48.1) than male infants (-48.5 g; 95% CI, -107.2 to 10.3). For female infants, SGA risk was greater in continuers than discontinuers (relative risk [RR],1.54; 95% CI, 1.02 to 2.32). Low birth weight risk was greater in continuers with 50% or more of days covered (RR, 1.69; 95% CI, 1.11 to 2.58) and exposure in the second trimester (RR, 1.53; 95% CI, 1.02 to 2.29), as compared with discontinuers. CONCLUSIONS: Depending on infant sex, as well as duration and timing of use, continuation of antidepressant use during pregnancy may be associated with lower infant birth weight, with corresponding increases in LBW and SGA.

Size of Lugol-unstained lesions as a predictor for risk of progression in premalignant lesions of the esophagus.

BACKGROUND AND AIMS: At present, the surveillance strategy for premalignant esophageal lesions in China is based solely on the pathologic diagnosis in Lugol's chromoendoscopy (LCE). In this study, we sought to determine the degree to which various unstained features under LCE may lead to improved ability to predict the risk of progression in esophageal lesions. METHODS: We re-examined and followed up on 1058 subjects who had Lugol-unstained lesions (LULs) together with a pathologic diagnosis that was lower than severe dysplasia at baseline screening based on a population-based randomized controlled trial over a median time of 5.8 years. We established a logistic regression model and calculated the adjusted cumulative incidence of severe dysplasia or malignancy. RESULTS: LUL size was predictive of progression to malignant lesions in individuals with a nondysplastic diagnosis (adjusted odd ratio6-10 mm vs ≤5 mm, 6.7; 95% confidence interval, 1.7-25.7; adjusted odds ratio>10 mm vs ≤5 mm, 27.9; 95% confidence interval, 7.3-105.7), and the corresponding adjusted cumulative incidence of malignant lesions was 3.6 and 13.2 per 100 persons. This is higher than that of small (≤5 mm) lesions, which showed mild dysplasia (2.7 per 100 persons), a condition for which surveillance every 3 years is recommended. Under the current approach, 65.3% of interval cancers missed at surveillance would be detected if individuals with medium (6-10 mm) and large (>10 mm) nondysplastic LULs were additionally monitored. CONCLUSIONS: We propose a modified surveillance strategy that combines findings under LCE examination and the pathologic analysis, where follow-up endoscopy is recommended for individuals with relatively large nondysplastic lesions.

Fontan-associated liver disease and total cavopulmonary anatomical flow effectors.

OBJECTIVE: We investigated a relationship between a composite index comprised of Fontan-circuit anatomical features and hepatic fibrosis scores from biopsy. METHODS: We identified living extracardiac Fontan patients, ≥7 years old and ≥5 but <20 years postoperative, that underwent cardiac catheterization and transvenous liver biopsy between March 2012 and September 2020. We divided patients into anatomical groups and applied a risk score to each patient. We compared average anatomical risk scores with average hepatic total fibrosis scores by group. RESULTS: We identified 111 patients that met inclusion criteria. After excluding four patients, we assigned 107 to one of 12 anatomical variant groups (n ≥ 3). For the 107, the average age at liver biopsy was 14 ± 6 years old. Of the 107, 105 (98%) were New York Heart Association Class 1. We found average anatomical risk scores by group correlated with average total fibrosis scores by group (R = 0.8; p = .005). An average Fontan duration to biopsy of 10 ± 1 years was similar for all 12 anatomical groups. We found no other clinical variables, laboratory, or hemodynamic values that trended with anatomical risk scores or hepatic total fibrosis scores. CONCLUSIONS: In a cohort of relatively young, stable extracardiac Fontan patients, average composite anatomical risk scores strongly correlated with average hepatic total fibrosis scores by anatomical group. These findings suggest that some anatomical variants in extracardiac Fontan patients are associated with higher Fontan-associated liver disease (FALD)-related hepatic total fibrosis scores than others, despite similar Fontan durations.

Maternal Gestational Weight Gain in Relation to Antidepressant Continuation in Pregnancy.

OBJECTIVE: Both excessive and inadequate gestational weight gain (GWG) are associated with adverse health outcomes for the woman and her child. Antidepressant use in pregnancy could affect GWG, based on evidence in nonpregnant women that some antidepressants may cause weight gain and others weight loss. Previous studies of antidepressant use and GWG were small with limited ability to account for confounding, including by maternal mental health status and severity. We assessed the association of antidepressant continuation in pregnancy with GWG among women using antidepressants before pregnancy. STUDY DESIGN: Our retrospective cohort study included singleton livebirths from 2001 to 2014 within Kaiser Permanente Washington, an integrated health care system. Data were obtained from electronic health records and linked Washington State birth records. Among women with ≥1 antidepressant fill within 6 months before pregnancy, women who filled an antidepressant during pregnancy were considered "continuers;" women without a fill were "discontinuers." We calculated mean differences in GWG and relative risks (RR) of inadequate and excessive weight gain based on Institute of Medicine guidelines. Using inverse probability of treatment weighting with generalized estimating equations, we addressed differences in maternal characteristics, including mental health conditions. RESULTS: Among the 2,887 births, 1,689 (59%) were to women who continued antidepressants in pregnancy and 1,198 (42%) were to discontinuers. After accounting for confounding, continuers had similar weight gain to those who discontinued (mean difference: 1.3 lbs, 95% confidence interval [CI]: -0.1 to 2.8 lbs) and similar risks of inadequate and excessive GWG (RR: 0.95, 95% CI: 0.80-1.14 and RR: 1.06, 95% CI: 0.98-1.14, respectively). Findings were comparable for specific antidepressants and trimesters of exposure. CONCLUSION: We did not find evidence that continuation of antidepressants in pregnancy led to differences in GWG. KEY POINTS: · Antidepressant use is associated with weight change in nonpregnant populations.. · Prior evidence on whether antidepressant use in pregnancy affects gestational weight gain is sparse.. · We accounted for confounding by characteristics such as mental health conditions and their severity.. · We found no association between pregnancy antidepressant continuation and gestational weight gain..

Management and Outcome of Pediatric Patients With Transient Small Bowel-Small Bowel Intussusception.

OBJECTIVE: The aim of this study was to assess the management and outcomes of healthy pediatric patients diagnosed radiologically with transient and benign small bowel-small bowel intussusception (SB-SBI). METHODS: Retrospective cohort study of healthy patients 0 to 18 years of age who presented to a children's hospital emergency department from January 1, 2005, to June 30, 2015, and had transient and benign SB-SBI characterized by spontaneous resolution (ie, transient), diameter of less than 2.5 cm, no lead point, normal bowel wall thickness, nondilated proximal small bowel, and no colonic involvement (ie, benign radiographic features). Charts were reviewed for demographics, clinical presentation, radiologic studies obtained, outcomes, and further management. Medical and radiologic records were also reviewed for 1 year after presentation for any subsequent pathologic diagnoses. RESULTS: Sixty-eight patients were included in our study, with a total of 87 episodes of transient and benign SB-SBI on initial or follow-up examination. Overall, 39 patients (57%) were admitted to the hospital, and 38 patients (56%) had a surgical consultation. Twenty-four patients (35%) had further radiologic studies obtained, including computed tomography scans, esophagogastroduodenoscopy, Meckel's scan, barium swallow studies, and magnetic resonance imaging. All studies were negative for concerning pathology including apparent lead points. None of the patients required surgical intervention or had any complications. CONCLUSIONS: Transient and benign SB-SBIs with reassuring radiologic and clinical features diagnosed in healthy pediatric patients are likely incidentally found and are unlikely to be associated with a pathologic lead point.

Management and Outcomes of Spontaneous Pneumomediastinum in Children.

OBJECTIVES: Management of spontaneous pneumomediastinum in the pediatric population is highly variable. There are limited data on the use of diagnostic tests and the need for admission. Our objectives were to characterize the management of pediatric spontaneous pneumomediastinum, determine the diagnostic yield of advanced imaging, and describe the patients' outcomes. METHODS: This is a retrospective cohort study of all patients presenting to a single tertiary pediatric emergency department between January 2008 and February 2015 diagnosed with pneumomediastinum. Patients were identified using 2 complementary strategies: International Classification of Diseases, Ninth Revision billing codes and a keyword search of the hospital radiology database. RESULTS: We identified 183 patients with spontaneous pneumomediastinum. The mean age was 12.8 ± 4.8 years. Diagnosis was established by chest radiograph (CXR) in 165 (90%) patients, chest computed tomography in 15 (8%), neck imaging in 2 (1%), and abdominal imaging in 1. After diagnosis, many patients underwent additional studies: repeat CXR (99, 54%), chest computed tomography (53, 29%), esophagram (45, 25%), and laryngoscopy (15, 8%). Seventy-eight percent of patients (n = 142) were admitted with a median length of stay of 27 hours (18.4-45.6 hours). Six patients returned to the emergency department within 96 hours for persistent chest pain; 2 were admitted, and 1 was found to have worsening pneumomediastinum on CXR. We performed a secondary analysis on 3 key subgroups: primary spontaneous pneumomediastinum (64, 35%), secondary gastrointestinal-associated pneumomediastinum (31, 17%), and secondary respiratory-associated pneumomediastinum (88, 48%). No patients in the study received an invasive intervention for pneumomediastinum. In all patients, further studies did not yield additional diagnostic information. CONCLUSIONS: Our data suggest that patients with spontaneous pneumomediastinum who are clinically well appearing can be managed conservatively with clinical observation, avoiding exposure to radiation and invasive procedures.

Integration of High-Resolution Radiation Detector for Hybrid Microchip Electrophoresis.

For decades, there has been immense progress in miniaturizing analytical methods based on electrophoresis to improve sensitivity and to reduce sample volumes, separation times, and/or equipment cost and space requirements, in applications ranging from analysis of biological samples to environmental analysis to forensics. In the field of radiochemistry, where radiation-shielded laboratory space is limited, there has been great interest in harnessing the compactness, high efficiency, and speed of microfluidics to synthesize short-lived radiolabeled compounds. We recently proposed that analysis of these compounds could also benefit from miniaturization and have been investigating capillary electrophoresis (CE) and hybrid microchip electrophoresis (hybrid-MCE) as alternatives to the typically used high-performance liquid chromatography (HPLC). We previously showed separation of the positron-emission tomography (PET) imaging tracer 3'-deoxy-3'-fluorothymidine (FLT) from its impurities in a hybrid-MCE device with UV detection, with similar separation performance to HPLC, but with improved speed and lower sample volumes. In this paper, we have developed an integrated radiation detector to enable measurement of the emitted radiation from radiolabeled compounds. Though conventional radiation detectors have been incorporated into CE systems in the past, these approaches cannot be readily integrated into a compact hybrid-MCE device. We instead employed a solid-state avalanche photodiode (APD)-based detector for real-time, high-sensitivity ß particle detection. The integrated system can reliably separate [18F]FLT from its impurities and perform chemical identification via coinjection with nonradioactive reference standard. This system can quantitate samples with radioactivity concentrations as low as 114 MBq/mL (3.1 mCi/mL), which is sufficient for analysis of radiochemical purity of radiopharmaceuticals.

Chest discomfort at night and risk of acute coronary syndrome: cross-sectional study of telephone conversations.

BACKGROUND: During telephone triage, it is difficult to assign adequate urgency to patients with chest discomfort. Considering the time of calling could be helpful. OBJECTIVE: To assess the risk of acute coronary syndrome (ACS) in certain time periods and whether sex influences this risk. METHODS: Cross-sectional study of 1655 recordings of telephone conversations of patients who called the out-of-hours services primary care (OHS-PC) for chest discomfort. Call time, patient characteristics, symptoms, medical history and urgency allocation of the triage conversations were collected. The final diagnosis of each call was retrieved at the patient's general practice. Absolute numbers of patients with and without ACS were plotted and risks per hour were calculated. The risk ratio of ACS at night (0 to 9 am) was calculated by comparing to the risk at other hours and was adjusted for gender and age. RESULTS: The mean age of callers was 58.9 (standard deviation ±19.5) years, 55.5% were women and, in total, 199 (12.0%) had an ACS. The crude risk ratio for an ACS at night was 1.80 (confidence interval 1.39-2.34, P < 0.001): 2.33 (1.68-3.22, P < 0.001) for men and 1.29 (0.83-1.99, P = 0.256) for women. The adjusted risk ratio for ACS of all people at night was 1.82 (1.07-3.10, P = 0.039). CONCLUSIONS: Patients calling the OHS-PC for chest discomfort between 0 and 9 am have almost twice a higher risk of ACS than those calling other hours, a phenomenon more evident in men than in women. At night, dispatching ambulances more 'straightaway' could be considered for these patients with chest discomfort. TRIAL NUMBER: NTR7331.