Transcriptome and functional analyses of phenotypic plasticity in sea grape Caulerpa okamurae.

Caulerpa is a marine green macroalga distinguished by a large single cell with multiple nuclei. It also exhibits remarkable morphological intraspecies variations, in response to diverse environmental types. However, the molecular mechanisms underlying this phenotypic plasticity remain poorly understood. In this work, we compare the transcriptomes of Caulerpa okamurae Weber Bosse, 1897 displaying altered phenotypes of cultivation and natural phenotypes and investigate significantly regulated genes and their biological functions using differential expression analyses. We observe light-harvesting complex upregulation and cellular framework stability downregulation in altered phenotypes compared to the natural phenotypes. Intertidal macrophytes reduce light capture to avoid photodamage and regulate their morphology to protect against wave damage. In contrast, the lower light conditions and the cultivation environment augment light capture and increase a morphology prioritizing light trapping. Moreover, the addition of simulated wave-sweeping stimuli induces a return to the natural morphology under high-light conditions, showing how mechanical stress affects morphological organization in C. okamurae. We provide detailed gene expression patterns in C. okamurae under varying light intensities and water conditions, suggesting a distinct influence on its morphological traits.

Role of Cerebral Embolic Protection Devices in Patients Undergoing Transcatheter Aortic Valve Replacement: An Updated Meta-Analysis.

BACKGROUND: Cerebral embolic protection devices (CEPD) capture embolic material in an attempt to reduce ischemic brain injury during transcatheter aortic valve replacement. Prior reports have indicated mixed results regarding the benefits of these devices. With new data emerging, we performed an updated meta-analysis examining the effect of CEPD during transcatheter aortic valve replacement on various clinical, neurological, and safety parameters. METHODS AND RESULTS: A comprehensive review of electronic databases was performed comparing CEPD and no-CEPD in transcatheter aortic valve replacement. Primary clinical outcome was all-cause stroke. Secondary clinical outcomes were disabling stroke and all-cause mortality. Neurological outcomes included worsening of the National Institutes of Health Stroke Scale score, Montreal Cognitive Assessment score from baseline at discharge, presence of new ischemic lesions, and total lesion volume on neuroimaging. Safety outcomes included major or minor vascular complications and stage 2 or 3 acute kidney injury. Seven randomized controlled trials with 4016 patients met the inclusion criteria. There was no statistically significant difference in the primary clinical outcome of all-cause stroke; secondary clinical outcomes of disabling stroke, all-cause mortality, neurological outcomes of National Institutes of Health Stroke Scale score worsening, Montreal Cognitive Assessment worsening, presence of new ischemic lesions, or total lesion volume on diffusion-weighted magnetic resonance imaging between CEPD versus control groups. There was no statistically significant difference in major or minor vascular complications or stage 2 or 3 acute kidney injury between the groups. CONCLUSIONS: The use of CEPD in transcatheter aortic valve replacement was not associated with a statistically significant reduction in the risk of clinical, neurological, and safety outcomes.

The effect of heterogeneous severe drought on all-cause and cardiovascular mortality in the Northern Rockies and Plains of the United States.

Drought is a distinct and complicated climate hazard that regularly leads to severe economic impacts. Changes in the frequency and occurrence of drought due to anthropogenic climate change can lead to new and unanticipated outcomes. To better prepare for health outcomes, more research is needed to develop methodologies to understand potential consequences. This study suggests a new methodology for assessing the impact of monthly severe drought exposure on mortality in the Northern Rockies and Plains of the United States from 2000 to 2018. A two-stage model with the power prior approach was applied to integrate heterogeneous severe drought pattern and estimate overall risk ratios of all-cause and cardiovascular mortality related to multiple drought indices (the US Drought Monitor, 6- and 12-month Standardized Precipitation-Evapotranspiration Index, 6- and 12 month Evaporative Demand Drought Index). Under severe drought, the risk ratios of all-cause mortality are 1.050 (95 % Cr: 1.031 to 1.071, USDM), 1.041 (95 % Cr: 1.022 to 1.060, 6-SPEI), 1.009 (95 % Cr: 0.989 to 1.031, 12SPEI), 1.045 (95 % Cr: 1.022 to 1.067, 6-EDDI), and 1.035 (95 % Cr: 1.009 to 1.062, 12-EDDI); cardiovascular mortality are 1.057 (95 % Cr: 1.023 to 1.091, USDM), 1.028 (95 % Cr: 0.998 to 1.059, 6-SPEI), 1.005 (95 % Cr: 0.973 to 1.040, 12-SPEI), 1.042 (95 % Cr: 1.005 to 1.080, 6-EDDI), and 1.004 (95 % Cr: 0.959 to 1.049, 12-EDDI). Our results showed that (i) a model with properly accounted for heterogeneous exposure pattern had greater risk ratios if statistically significant; (ii) a mid-term (6-month) severe drought had higher risk ratios compared to longer-term (12-month) drought; and (iii) different severe droughts affect populations in a different way. These results expand the existing knowledge of drought relationship to increasing mortality in the United States. The findings from this study highlight the need for communities and policymakers to establish effective drought-prevention initiatives in this region.

Outcomes of Prediabetes Compared with Normoglycaemia and Diabetes Mellitus in Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-analysis.

Background: Patients with prediabetes are at increased risk of coronary artery disease (CAD). However, the association between prediabetes and adverse clinical outcomes following percutaneous coronary intervention (PCI) is inconsistent, in contrast to outcomes in patients with diabetes mellitus (DM). Thus, this meta-analysis evaluated the impact of dysglycaemia on PCI outcomes. Methods: The PubMed, Embase, Cochrane, and ClinicalTrials.gov databases were systematically reviewed from inception of databases until June 2022. In 17 studies, outcomes of PCI in patients with prediabetes were compared with patients who were normoglycaemic, and patients with DM. The primary outcome was all-cause mortality at the longest follow-up. Results: Included were 12 prospective and five retrospective studies, with 11,868, 14,894 and 13,536 patients undergoing PCI in the prediabetes, normoglycaemic and DM groups, respectively. Normoglycaemic patients had a statistically lower risk of all-cause mortality, (risk ratio [RR] 0.66, 95% confidence interval [CI] 0.52-0.84), myocardial infarction (MI; RR 0.76, 95% CI 0.61-0.95) and cardiac mortality (RR 0.58, 95% CI 0.39-0.87) compared with prediabetic patients undergoing PCI at the longest follow-up. Patients with prediabetes had a lower risk of all-cause mortality (RR=0.72 [95% CI 0.53-0.97]) and cardiac mortality (RR =0.47 [95% CI 0.23-0.93]) compared with patients with DM who underwent PCI. Conclusion: Among patients who underwent PCI for CAD, the risk of all-cause and cardiac mortality, major adverse cardiovascular events and MI in prediabetic patients was higher compared with normoglycaemic patients but lower compared with patients with DM.

The Association between Drought Exposure and Respiratory-Related Mortality in the United States from 2000 to 2018.

Climate change has brought increasing attention to the assessment of health risks associated with climate and extreme events. Drought is a complex climate phenomenon that has been increasing in frequency and severity both locally and globally due to climate change. However, the health risks of drought are often overlooked, especially in places such as the United States, as the pathways to health impacts are complex and indirect. This study aims to conduct a comprehensive assessment of the effects of monthly drought exposure on respiratory mortality for NOAA climate regions in the United States from 2000 to 2018. A two-stage model was applied to estimate the location-specific and overall effects of respiratory risk associated with two different drought indices over two timescales (the US Drought Monitor and the 6-month and 12-month Evaporative Demand Drought Index). During moderate and severe drought exposure, respiratory mortality risk ratio in the general population increased up to 6.0% (95% Cr: 4.8 to 7.2) in the Northeast, 9.0% (95% Cr: 4.9 to 13.3) in the Northern Rockies and Plains, 5.2% (95% Cr: 3.9 to 6.5) in the Ohio Valley, 3.5% (95% Cr: 1.9 to 5.0) in the Southeast, and 15.9% (95% Cr: 10.8 to 20.4) in the Upper Midwest. Our results showed that age, ethnicity, sex (both male and female), and urbanicity (both metro and non-metro) resulted in more affected population subgroups in certain climate regions. The magnitude and direction of respiratory risk ratio differed across NOAA climate regions. These results demonstrate a need for policymakers and communities to develop more effective strategies to mitigate the effects of drought across regions.

Role of social determinants of health in differential respiratory exposure and health outcomes among children.

BACKGROUND: Attributes defining the Social Determinants of Health (SDoH) are associated with disproportionate exposures to environmental hazards and differential health outcomes among communities. The dynamics between SDoH, disproportionate environmental exposures, and differential health outcomes are often specific to micro-geographic areas. METHODS: This study focused on children less than 20 years of age who lived in Douglas County, Nebraska, during 2016-2019. To assess the role of SDoH in differential exposures, we evaluated the association between SDoH metrics and criteria pollutant concentrations and the association between SDoH and pediatric asthma exacerbations to quantify the role of SDoH in differential pediatric asthma outcomes. The Bayesian Poisson regression model with spatial random effects was used to evaluate associations. RESULTS: We identified significant positive associations between the annual mean concentration of criteria pollutants (carbon monoxide, particulate matter2.5, nitrogen dioxide, sulfur dioxide) with race (Non-Hispanic Black and Hispanic/Latino), financial stability, and literacy. Additionally, there were significant positive associations between higher rates of pediatric asthma emergency department visits and neighborhoods with more Non-Hispanic Black children, children without health insurance coverage, and households without access to a vehicle. CONCLUSIONS: Non-Hispanic Black and Hispanic/Latino children living in Douglas County, NE experience disproportionately higher exposure to criteria pollutant concentrations. Additionally, higher rates of asthma exacerbations among Non-Hispanic Black children could be due to reduced access to respiratory care that is potentially the result of financial instability and vehicle access. These results could inform city planners and health care providers to mitigate respiratory risks among these higher at-risk populations.

Vehicle Control as a Measure of Real-World Driving Performance in Patients With Rheumatoid Arthritis.

OBJECTIVE: To quantify vehicle control as a metric of automobile driving performance in patients with rheumatoid arthritis (RA). METHODS: Naturalistic driving assessments were completed in patients with active RA and controls without disease. Data were collected using in-car, sensor-based instrumentation installed in the participants' own vehicles to observe typical driving habits. RA disease status, disease activity, and functional status were associated with vehicle control (lateral [steering] and longitudinal [braking/accelerating] acceleration variability) using mixed-effect linear regression models stratified by road type (defined by roadway speed limit). RESULTS: Across 1,292 driving hours, RA drivers (n = 33) demonstrated differences in vehicle control compared to controls (n = 23), with evidence of significant statistical interaction between disease status and road type (P < 0.001). On residential roads, participants with RA demonstrated overall lower braking/accelerating variability than controls (P ≤ 0.004) and, when disease activity was low, lower steering variability (P = 0.03). On interstates/highways, RA was associated with increased steering variability among those with moderate/high Clinical Disease Activity Index scores (P = 0.04). In models limited to RA, increases in disease activity and physical disability over 12 weeks of observation were associated with a significant increase in braking/accelerating variability on interstate/highways (both P < 0.05). CONCLUSION: Using novel naturalistic assessments, we linked RA and worsening RA disease severity with aberrant vehicle control. These findings support the need for further research to map these observed patterns in vehicle control to metrics of driver risk and, in turn, to link patterns of real-world driving behavior to diagnosis and disease activity.

Joint association between ambient air pollutant mixture and pediatric asthma exacerbations.

Exposure to air pollutants is known to exacerbate asthma, with prior studies focused on associations between single pollutant exposure and asthma exacerbations. As air pollutants often exist as a complex mixture, there is a gap in understanding the association between complex air pollutant mixtures and asthma exacerbations. We evaluated the association between the air pollutant mixture (52 pollutants) and pediatric asthma exacerbations. Method: This study focused on children (age ≤ 19 years) who lived in Douglas County, Nebraska, during 2016-2019. A seasonal-scale joint association between the outdoor air pollutant mixture adjusting for potential confounders (temperature, precipitation, wind speed, and wind direction) in relation to pediatric asthma exacerbation-related emergency department (ED) visits was evaluated using the generalized weighted quantile sum (qWQS) regression with repeated holdout validation. Results: We observed associations between air pollutant mixture and pediatric asthma exacerbations during spring (lagged by 5 days), summer (lag 0-5 days), and fall (lag 1-3 days) seasons. The estimate of the joint outdoor air pollutant mixture effect was higher during the summer season (adjusted-ßWQS = 1.11, 95% confidence interval [CI]: 0.66, 1.55), followed by spring (adjusted-ßWQS = 0.40, 95% CI: 0.16, 0.62) and fall (adjusted-ßWQS = 0.20, 95% CI: 0.06, 0.33) seasons. Among the air pollutants, PM2.5, pollen, and mold contributed higher weight to the air pollutant mixture. Conclusion: There were associations between outdoor air pollutant mixture and pediatric asthma exacerbations during the spring, summer, and fall seasons. Among the 52 outdoor air pollutant metrics investigated, PM2.5, pollen (sycamore, grass, cedar), and mold (Helminthosporium, Peronospora, and Erysiphe) contributed the highest weight to the air pollutant mixture.

Prediction of Stability during Walking at Simulated Ship's Rolling Motion Using Accelerometers.

Due to a ship's extreme motion, there is a risk of injuries and accidents as people may become unbalanced and be injured or fall from the ship. Thus, individuals must adjust their movements when walking in an unstable environment to avoid falling or losing balance. A person's ability to control their center of mass (COM) during lateral motion is critical to maintaining balance when walking. Dynamic balancing is also crucial to maintain stability while walking. The margin of stability (MOS) is used to define this dynamic balancing. This study aimed to develop a model for predicting balance control and stability in walking on ships by estimating the peak COM excursion and MOS variability using accelerometers. We recruited 30 healthy individuals for this study. During the experiment, participants walked for two minutes at self-selected speeds, and we used a computer-assisted rehabilitation environment (CAREN) system to simulate the roll motion. The proposed prediction models in this study successfully predicted the peak COM excursion and MOS variability. This study may be used to protect and save seafarers or passengers by assessing the risk of balance loss.

Drought and all-cause mortality in Nebraska from 1980 to 2014: Time-series analyses by age, sex, race, urbanicity and drought severity.

BACKGROUND: Climate change will increase drought duration and severity in many regions around the world, including the Central Plains of North America. However, studies on drought-related health impacts are still sparse. This study aims to explore the potential associations between drought and all-cause mortality in Nebraska from 1980 to 2014. METHODS: The Evaporative Demand Drought Index (EDDI) were used to define short-, medium- and long-term drought exposures, respectively. We used a Bayesian zero-inflated censored negative binomial (ZICNB) regression model to estimate the overall association between drought and annual mortality first in the total population and second in stratified sub-populations based on age, race, sex, and the urbanicity class of the counties. RESULTS: The main findings indicate that there is a slightly negative association between all-cause mortality and all types of droughts in the total population, though the effect is statistically null. The joint-stratified analysis renders significant results for a few sub-groups. White population aged 25-34 and 45-64 in metro counties and 45-54 in non-metro counties were the population more at risk in Nebraska. No positive associations were observed in any race besides white. Black males aged 20-24 and white females older than 85 showed protective effect against drought mainly in metro counties. We also found that more sub-populations had higher rates of mortality with longer-term droughts compared to shorter-term droughts (12-month vs 1- or 6-month timescales), in both metro and non-metro counties, collectively. CONCLUSION: Our results suggest that mortality in middle aged white population in Nebraska shows a greater association with drought. Moreover, women aged 45-54 were more affected than men in non-metro counties. With a projected increase in the frequency and severity of drought due to climate change, understanding these relationships between drought and human health will better inform drought mitigation planning to reduce potential impacts.

Urinary BA Indices as Prognostic Biomarkers for Complications Associated with Liver Diseases.

Hepatobiliary diseases and their complications cause the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues, which may exacerbate the underlying condition and lead to unfavorable prognosis. To develop and validate prognostic biomarkers for the prediction of complications of cholestatic liver disease based on urinary BA indices, liquid chromatography-tandem mass spectrometry was used to analyze urine samples from 257 patients with cholestatic liver diseases during a 7-year follow-up period. The urinary BA profile and non-BA parameters were monitored, and logistic regression models were used to predict the prognosis of hepatobiliary disease-related complications. Urinary BA indices were applied to quantify the composition, metabolism, hydrophilicity, and toxicity of the BA profile. We have developed and validated the bile-acid liver disease complication (BALDC) model based on BA indices using logistic regression model, to predict the prognosis of cholestatic liver disease complications including ascites. The mixed BA and non-BA model was the most accurate and provided higher area under the receiver operating characteristic (ROC) and smaller akaike information criterion (AIC) values compared to both non-BA and MELD (models for end stage liver disease) models. Therefore, the mixed BA and non-BA model could be used to predict the development of ascites in patients diagnosed with liver disease at early stages of intervention. This will help physicians to make a better decision when treating hepatobiliary disease-related ascites.

Wearable Sensor-Based Prediction Model of Timed up and Go Test in Older Adults.

The Timed Up and Go (TUG) test has been frequently used to assess the risk of falls in older adults because it is an easy, fast, and simple method of examining functional mobility and balance without special equipment. The purpose of this study is to develop a model that predicts the TUG test using three-dimensional acceleration data collected from wearable sensors during normal walking. We recruited 37 older adults for an outdoor walking task, and seven inertial measurement unit (IMU)-based sensors were attached to each participant. The elastic net and ridge regression methods were used to reduce gait feature sets and build a predictive model. The proposed predictive model reliably estimated the participants' TUG scores with a small margin of prediction errors. Although the prediction accuracies with two foot-sensors were slightly better than those of other configurations (e.g., MAPE: foot (0.865 s) > foot and pelvis (0.918 s) > pelvis (0.921 s)), we recommend the use of a single IMU sensor at the pelvis since it would provide wearing comfort while avoiding the disturbance of daily activities. The proposed predictive model can enable clinicians to assess older adults' fall risks remotely through the evaluation of the TUG score during their daily walking.

Meta-Analysis of Transradial vs Transfemoral Access for Percutaneous Coronary Intervention in Patients With ST Elevation Myocardial Infarction.

Transradial access (TRA) has emerged as an alternative to transfemoral access (TFA) for percutaneous coronary intervention (PCI) in ST elevation myocardial infarction (STEMI) patients. However, the rate of TRA adoption has been much slower in the acute coronary syndrome (ACS) patient population. This meta-analysis was conducted to assess clinical outcomes of TRA compared with TFA in STEMI patients undergoing PCI. A manual search of PubMed, EMBASE, Cochrane library database, Cumulative Index to Nursing and Allied Health Literature (CINAHL), ClinicalTrials.gov, and recent major scientific conference sessions from inception to October 15th, 2019 was performed. Primary outcomes in our analysis were all-cause mortality and trial-defined major bleeding. Secondary outcomes included vascular complications, myocardial infarction, stroke, procedure, and fluoroscopy time. 17 randomized controlled trials (RCTs) (N = 12,018) met inclusion criteria. TRA was associated with lower all-cause mortality (risk ratio [RR]: 0.71, 95% confidence interval [CI]: 0.57 to 0.88), major bleeding (RR: 0.59, 95%CI: 0.45 to 0.77), and vascular complications (RR: 0.42, 95%CI: 0.32 to 0.56) compared with TFA. There was no difference in the incidence of myocardial infarction (MI), stroke, or procedure duration between the 2 groups. The difference in all-cause mortality between TRA and TFA was statistically nonsignificant when major bleeding was held constant. In conclusion, TRA was associated with lower risk of all-cause mortality, major bleeding, and vascular complications compared with TFA in STEMI patients undergoing PCI.

Multivessel Versus Culprit-Only Revascularization in STEMI and Multivessel Coronary Artery Disease: Meta-Analysis of Randomized Trials.

OBJECTIVES: The goal of this systematic review and meta-analysis was to provide a comprehensive evaluation of contemporary randomized trials addressing the efficacy and safety of multivessel versus culprit vessel-only percutaneous coronary intervention (PCI) among patients presenting with ST-segment elevation myocardial infarction and multivessel coronary artery disease. BACKGROUND: Multivessel coronary artery disease is present in about one-half of patients with ST-segment elevation myocardial infarction. Randomized controlled trials comparing multivessel and culprit vessel-only PCI produced conflicting results regarding the benefits of a multivessel PCI strategy. METHODS: A comprehensive search for published randomized controlled trials comparing multivessel PCI with culprit vessel-only PCI was conducted on ClinicalTrials.gov, PubMed, Web of Science, EBSCO Services, the Cochrane Central Register of Controlled Trials, Google Scholar, and scientific conference sessions from inception to September 15, 2019. A meta-analysis was performed using a random-effects model to calculate the risk ratio (RR) and 95% confidence interval (CI). Primary efficacy outcomes were all-cause mortality and reinfarction. RESULTS: Ten randomized controlled trials were included, representing 7,030 patients: 3,426 underwent multivessel PCI and 3,604 received culprit vessel-only PCI. Compared with culprit vessel-only PCI, multivessel PCI was associated with no significant difference in all-cause mortality (RR: 0.85; 95% CI: 0.68 to 1.05) and lower risk for reinfarction (RR: 0.69; 95% CI: 0.50 to 0.95), cardiovascular mortality (RR: 0.71; 95% CI: 0.50 to 1.00), and repeat revascularization (RR: 0.34; 95% CI: 0.25 to 0.44). Major bleeding (RR: 0.92; 95% CI: 0.50 to 1.67), stroke (RR: 1.15; 95% CI: 0.65 to 2.01), and contrast-induced nephropathy (RR: 1.25; 95% CI: 0.80 to 1.95) were not significantly different between the 2 groups. CONCLUSIONS: Multivessel PCI was associated with a lower risk for reinfarction, without any difference in all-cause mortality, compared with culprit vessel-only PCI in patients with ST-segment elevation myocardial infarction.

Safety and efficacy of leadless pacemaker for cardioinhibitory vasovagal syncope.

BACKGROUND: Single-chamber leadless pacemakers (LPs) have been shown to be an effective alternative to conventional transvenous pacemakers (CTPs), but their benefit in the context of cardioinhibitory vasovagal syncope (CI-VVS) is unknown. OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of LP compared with dual-chamber CTP for CI-VVS. METHODS: We conducted a multicenter, retrospective study comparing patients who received LP or dual-chamber CTP for drug-refractory CI-VVS. CI-VVS was diagnosed clinically and supported by cardiac monitoring and head-up tilt table testing. The primary efficacy endpoint was freedom from syncope during follow-up. Secondary endpoints included device efficacy and safety estimated by device-related major and minor adverse events (AEs). RESULTS: Seventy-two patients (24 LP, 48 CTP; age 32 ± 5.5 years; 90% female; syncope frequency 7.6 ± 3.4 per year) were included. At 1 year, 91% of patients (22/24) in the LP group and 94% of patients (43/48) in the CTP group met the primary efficacy endpoint (P = .7). Device efficacy endpoint was met in 92% of the LP group and 98% of the CTP group (P = .2). Early major AEs occurred in 2 of 24 in the LP group and 3 of 48 in the CTP group (P = .4). Late major AEs occurred in 0 of 24 in the LP group and 2 of 48 in the CTP group (P = 1). CONCLUSION: In patients with CI-VVS, single-chamber LP demonstrated equivalent efficacy in reducing syncopal events compared to dual-chamber CTP, with a similar safety profile.

Network meta-regression for ordinal outcomes: Applications in comparing Crohn's disease treatments.

Crohn's disease (CD) is a life-long condition associated with recurrent relapses characterized by abdominal pain, weight loss, anemia, and persistent diarrhea. In the US, there are approximately 780 000 CD patients and 33 000 new cases added each year. In this article, we propose a new network meta-regression approach for modeling ordinal outcomes in order to assess the efficacy of treatments for CD. Specifically, we develop regression models based on aggregate covariates for the underlying cut points of the ordinal outcomes as well as for the variances of the random effects to capture heterogeneity across trials. Our proposed models are particularly useful for indirect comparisons of multiple treatments that have not been compared head-to-head within the network meta-analysis framework. Moreover, we introduce Pearson residuals and construct an invariant test statistic to evaluate goodness-of-fit in the setting of ordinal outcome data. A detailed case study demonstrating the usefulness of the proposed methodology is carried out using aggregate ordinal outcome data from 16 clinical trials for treating CD.

Plasma and intracellular pharmacokinetics of tenofovir disoproxil fumarate and emtricitabine in transgender women receiving feminizing hormone therapy.

BACKGROUND: Transwomen have an increased risk of HIV acquisition compared with other adults. Drug-drug interactions between pre-exposure prophylaxis (PrEP) and gender-affirming therapy are cited as a reason for poor PrEP uptake among transwomen. We evaluated plasma tenofovir and emtricitabine pharmacokinetics and their active intracellular anabolites, tenofovir-diphosphate and emtricitabine-triphosphate, in transwomen receiving feminizing hormones. METHODS: We enrolled HIV-negative transwomen (≥19 years) not receiving PrEP. Participants took oral tenofovir disoproxil fumarate/emtricitabine 300/200 mg daily for 14 days. Plasma was collected at 0 h (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 and 12 h on day 14 post-tenofovir disoproxil fumarate/emtricitabine dose. The plasma AUC0-24 was calculated using the trapezoidal rule and compared with historical HIV-negative cisgender adults as geometric mean ratios (GMRs, 90% CI). Secondarily, tenofovir-diphosphate and emtricitabine-triphosphate from PBMCs collected at 0 h and 12 h were reported descriptively as geometric means (90% CI). Clinical trials registration: NCT03270969. RESULTS: Among 15 transwomen (mean age 32 years), geometric mean tenofovir and emtricitabine plasma AUC0-24 were lower compared with controls: tenofovir, 2.10 versus 2.76 mg·h/L, GMR 0.76 (0.65-0.90), P = 0.01; emtricitabine, 9.15 versus 10.64 mg·h/L, GMR 0.86 (0.75-0.98), P = 0.07. Tenofovir-diphosphate and emtricitabine-triphosphate concentrations were higher than previously reported in the literature: 167.1 (146.6-190.5) fmol/106 cells and 15.4 (13.8-17.3) pmol/106 cells, respectively. CONCLUSIONS: We observed lower plasma tenofovir and emtricitabine concentrations in transwomen compared with historical cisgender adults, yet intracellular tenofovir-diphosphate and emtricitabine-triphosphate concentrations were higher than previously reported in PBMCs. Understanding the differences of PrEP pharmacokinetics in plasma and tissue compartments and the resultant impact on efficacy remains important for transwomen.

Intracardiac echocardiography versus transesophageal echocardiography for left atrial appendage closure: an updated meta-analysis and systematic review.

Intracardiac echocardiography (ICE) has emerged as an alternative to transesophageal echocardiography (TEE) to guide implantation of percutaneous left atrial appendage closure (LAAC) devices in patients with atrial fibrillation (AF) and a high bleeding risk. We reviewed the efficacy and safety of ICE compared to TEE in LAAC in this updated meta-analysis. Medline, CINAHL, EMBASE and Scopus were systematically searched for studies comparing ICE and TEE in percutaneous LAAC. Our primary outcomes of interest were procedural success and study reported periprocedural complications. Secondary outcomes included various procedural characteristics. Risk ratios (RR), standardized mean differences (SMD) and their corresponding 95% confidence intervals (CI) were calculated. The analysis was performed using a random-effect model. Nine observational studies met our inclusion criteria with a total of 2620 patients (ICE: 679 and TEE: 1941). Mean CHA2DS2-Vasc (4.4 ± 0.3 for ICE vs 4.5 ± 0.3 for TEE, P = 0.60) and HAS-BLED (3.2 ± 0.4 vs 3.1 ± 0.6, P = 0.78) scores were comparable between the two groups. There was no significant difference in procedure success rate (RR: 1.01, 95% CI: 0.99-1.02, P= 0.31) and periprocedural complications (RR: 0.85, 95% CI: 0.59-1.23, P = 0.39). No significant difference was observed in procedure duration, fluoroscopy time and contrast volume used while a trend towards decreased hospital length of stay was seen with the use of ICE. Thus, our updated meta-analysis shows ICE is as effective and safe as TEE for implantation of LAAC devices.