Colorectal Cancer Screening Rates at Federally Qualified Health Centers From 2014 to 2022: Incomplete Recovery From COVID-19 and Worsening Disparities.

INTRODUCTION: Federally Qualified Health Centers (FQHC) provide preventive health services such as colorectal cancer (CRC) screening to low-income and underinsured individuals. Overall CRC screening participation in the United States declined during the COVID-19 pandemic and recovered by 2021; however, trends in underresourced settings are unknown. METHODS: Using Uniform Data System data from 2014 to 2022, we assessed trends in FQHC CRC screening rates nationally, in California, and in Los Angeles County and determined clinic-level factors associated with recent screening rate changes. For each FQHC, we calculated the screening rate change from 2019 to 2020, 2020 to 2021, and 2020 to 2022. We used mixed-effects linear regression to determine clinic-level characteristics associated with each screening rate change. RESULTS: Across all FQHC (n = 1,281), 7,016,181 patients were eligible for CRC screening in 2022. Across the United States and in California, median screening rates increased from 2014 to 2019, severely declined in 2020, and failed to return to prepandemic levels by 2022. Both nationally and in California, CRC screening declined most dramatically from 2019 to 2020 in FQHC serving majority Hispanic/Latino patients or a high proportion of patients experiencing homelessness. From 2020 to 2022, screening rates did not recover completely in US FQHC, with disproportionate recovery among FQHC serving majority non-Hispanic Black patients. DISCUSSION: CRC screening rates at FQHC did not return to prepandemic levels by 2022, and recovery varied by FQHC patient characteristics. Tailored interventions addressing low and decreasing CRC screening rates in FQHC are urgently needed to mitigate worsening CRC disparities.

Association of vena cava filters and catheter-directed thrombolysis for deep vein thrombosis with hospital readmissions.

BACKGROUND: Acute deep vein thrombosis (DVT) affects >350,000 patients each year in the United States. Contemporary rehospitalization rates and predictors of acute DVT have not been well-characterized. We aimed to evaluate the all-cause 30-day readmission rate and its association with catheter-directed thrombolysis and vena cava filters in patients with proximal and caval DVT. METHODS: Patients with an index hospitalization for acute proximal lower extremity DVT were evaluated for unplanned readmission rates at 30 days using the Nationwide Readmission Database from 2016 to 2017. We used Cox proportional hazard model to determine the predictors of 30-day readmissions and their association with inferior vena cava (IVC) filter and CDT use. RESULTS: We identified 58,306 adult patients with an index hospitalization for acute proximal DVT. The unplanned 30-day rehospitalization rate was 14.7% (95% confidence interval [CI], 14.5-15.0%). There were 4995 patients (10.0%) who underwent CDT and 6085 (12.2%) who underwent IVC filter placement. In multivariable analysis, only CDT was associated with a lower hazard for rehospitalization (hazard ratio [HR], 0.77; 95% CI, 0.71-0.84; P < .001), whereas IVC filter placement (HR, 1.26; 95% CI, 1.19-1.34; P < .001), Charlson Comorbidity Index of >3 (HR, 1.47; 95% CI, 1.38-1.56; P < .001), malignancy (HR, 1.45; 95% CI, 1.34-1.57; P < .001), and length of stay >5 days (HR, 1.39; 95% CI, 1.33-1.46; P < .001), and acute kidney injury (HR, 1.18; 95% CI, 1.11-1.25; P < .001) were associated with higher readmission rates. CONCLUSIONS: The 30-day unplanned rehospitalization rate continues to be high in patients with acute proximal DVT. CDT was associated with lower rehospitalization rates, whereas IVC filter placement was associated with increased rehospitalization rates.

The Impact of Renal Function on Hepatic Encephalopathy Following TIPS Placement for Refractory Ascites.

BACKGROUND: The impact of renal function on hepatic encephalopathy (HE) following transjugular intrahepatic portosystemic shunt (TIPS) placement for refractory ascites is poorly understood. We investigated the role of renal function on HE following TIPS placement. METHODS: A retrospective study was performed for patients undergoing TIPS for refractory ascites from 2007-2019. Patients were stratified by GFR at time of TIPS placement and by whether they were on hemodialysis (HD). Chronic kidney disease (CKD) stage 3 or higher was defined as pre-TIPS GFR < 60 for at least 3 months. Logistic regression analyses were used to identify the role of GFR and CKD at time of TIPS placement on HE within 60 days post TIPS placement. RESULTS: Among 201 TIPS patients for refractory ascites (61% male; mean age 59.1), 78 (39%) patients were in CKD, and 16 (21%) were on HD. Mean GFR at time of TIPS placement was 62.7 ± 28.2 for all non-HD patients (n = 185). Compared with the GFR ≥ 90 group, GFR < 30 or HD (OR, 3.56; 95%CI, 1.19-10.7; p = 0.023) and CKD (OR, 2.52; 95%CI, 1.40-4.53; p = 0.002) at time of TIPS placement were significant predictors of post-TIPS placement HE within 60 days. GFRs between 30-60 and 60-90 were not significant predictors. CONCLUSIONS: In TIPS patients for recurrent ascites, patients with acutely impaired renal function or chronic renal dysfunction were at an increased risk for HE after TIPS.

Fecal matters: Microbial signatures distinguish clinically relevant subtypes of precancerous colorectal polyps.

Colorectal cancer (CRC) can arise from adenomatous or serrated polyps, which differ in their detection rate and risk of cancer progression. In this issue, Lee et al. report that these polyp subtypes demonstrate distinct fecal microbial species composition and metabolic potential that associate with diet and medications.

Anticoagulation for the Treatment of Portal Vein Thrombosis in Cirrhosis: A Systematic Review and Meta-Analysis of Comparative Studies.

Background: Portal vein thrombosis (PVT) leads to significant morbidity and mortality burden in patients with cirrhosis. An improved understanding of the utility of anticoagulation in patients with PVT will aid clinical decision making and inform future research. This meta-analysis aimed to evaluate the association between anticoagulation therapy and clinical outcomes in the context of treatment for PVT in cirrhosis. Methods: Pubmed, Embase, and Web of Science were searched from inception to February 13, 2022, for studies comparing the use of anticoagulation to other modalities as treatment for PVT in cirrhosis. Pooled odds ratios (OR) were calculated using a random-effects model for PVT improvement, recanalization, progression, bleeding events, and all-cause mortality in treatment studies. Results: We identified 944 records, of which 16 studies (n = 1126) examining anticoagulation as PVT treatment were included for subsequent analysis. Anticoagulation as PVT treatment was associated with PVT improvement (OR 3.64; 95% CI 2.56-5.17), PVT recanalization (OR 3.73; 95% CI 2.45-5.68), decreased PVT progression (OR 0.38; 95% CI 0.23-0.63), and decreased all-cause mortality (OR 0.47; 95% CI 0.29-0.75). The use of anticoagulation was not associated with bleeding events (OR 0.80; 95% CI 0.39-1.66). All analyses demonstrated low heterogeneity. Conclusions: These results support the use of anticoagulation in cirrhosis as treatment for PVT. These findings may inform the clinical management of PVT and highlight the need for further studies such as large randomized controlled trials characterizing the safety and efficacy of anticoagulation for PVT in cirrhosis.

Deep Learning Model for Static Ocular Torsion Detection Using Synthetically Generated Fundus Images.

Purpose: The objective of the study is to develop deep learning models using synthetic fundus images to assess the direction (intorsion versus extorsion) and amount (physiologic versus pathologic) of static ocular torsion. Static ocular torsion assessment is an important clinical tool for classifying vertical ocular misalignment; however, current methods are time-intensive with steep learning curves for frontline providers. Methods: We used a dataset (n = 276) of right eye fundus images. The disc-foveal angle was calculated using ImageJ to generate synthetic images via image rotation. Using synthetic datasets (n = 12,740 images per model) and transfer learning (the reuse of a pretrained deep learning model on a new task), we developed a binary classifier (intorsion versus extorsion) and a multiclass classifier (physiologic versus pathologic intorsion and extorsion). Model performance was evaluated on unseen synthetic and nonsynthetic data. Results: On the synthetic dataset, the binary classifier had an accuracy and area under the receiver operating characteristic curve (AUROC) of 0.92 and 0.98, respectively, whereas the multiclass classifier had an accuracy and AUROC of 0.77 and 0.94, respectively. The binary classifier generalized well on the nonsynthetic data (accuracy = 0.94; AUROC = 1.00). Conclusions: The direction of static ocular torsion can be detected from synthetic fundus images using deep learning methods, which is key to differentiate between vestibular misalignment (skew deviation) and ocular muscle misalignment (superior oblique palsies). Translational Relevance: Given the robust performance of our models on real fundus images, similar strategies can be adopted for deep learning research in rare neuro-ophthalmologic diseases with limited datasets.

Microbiome Therapeutics for Food Allergy.

The prevalence of food allergies continues to rise, and with limited existing therapeutic options there is a growing need for new and innovative treatments. Food allergies are, in a large part, related to environmental influences on immune tolerance in early life, and represent a significant therapeutic challenge. An expanding body of evidence on molecular mechanisms in murine models and microbiome associations in humans have highlighted the critical role of gut dysbiosis in the pathogenesis of food allergies. As such, the gut microbiome is a rational target for novel strategies aimed at preventing and treating food allergies, and new methods of modifying the gastrointestinal microbiome to combat immune dysregulation represent promising avenues for translation to future clinical practice. In this review, we discuss the intersection between the gut microbiome and the development of food allergies, with particular focus on microbiome therapeutic strategies. These emerging microbiome approaches to food allergies are subject to continued investigation and include dietary interventions, pre- and probiotics, microbiota metabolism-based interventions, and targeted live biotherapeutics. This exciting frontier may reveal disease-modifying food allergy treatments, and deserves careful study through ongoing clinical trials.

Endovascular therapy for superior vena cava syndrome: A systematic review and meta-analysis.

BACKGROUND: Superior vena cava (SVC) syndrome is caused by the obstruction of the SVC and can result in significant morbidity and mortality. In contemporary practice, endovascular therapy (ET) has become the standard of care for a majority of these patients. This study is a systematic review and meta-analysis of the available literature to assess technical success, restenosis, and recurrence of SVC syndrome following endovascular intervention. METHODS: For this meta-analysis, we conducted a systematic literature review of PubMed, Cochrane Library, and Embase databases from inception to April 14, 2021 for studies on ET for SVC syndrome. Studies included full-length journal articles on the use of ET among adults with SVC syndrome. Case reports or case series with fewer than 20 patients were excluded. We evaluated the endpoints of technical success rate, restenosis rate, and recurrence rates in SVC syndrome patients after endovascular stenting. The results of this study were calculated using random-effects models. FINDINGS: We identified 6,012 reports, of which 39 studies met our inclusion criteria and were included for analysis. A total of 2200 patients received ET for SVC syndrome. The weighted technical success rate was 98.8% (95% CI 98.2-99.3) with low heterogeneity (I2=17.4%, p = 0.185), restenosis rate was 10.5% (95% CI 8.4-12.6) with moderate heterogeneity (I2=53.5%, p<0.001), and recurrence rate was 10.8% (95% CI 8.1-13.5) with high heterogeneity (I2=75.8%, p<0.001). Total complication rate was 8.6% (95% CI 7.3%-9.9%) with a mean complication rate of 7.5% (95% CI 4.7%-10.3%). INTERPRETATION: Our systematic review revealed high technical success, low restenosis, and low recurrence rates following ET. Collectively, these results support the paradigm of ET as an effective and safe treatment for patients with SVC syndrome. FUNDING: None.

History of Hepatic Encephalopathy Is Not a Contraindication to Transjugular Intrahepatic Portosystemic Shunt Placement for Refractory Ascites.

INTRODUCTION: The outcomes of transjugular intrahepatic portosystemic shunt (TIPS) placement in patients with hepatic encephalopathy (HE) are controversial. We studied the relationship of pre-TIPS HE in patients undergoing TIPS for refractory ascites on all-cause mortality and development of post-TIPS HE. METHODS: A single-center retrospective comparison study was performed for patients undergoing TIPS for refractory ascites. Survival by history of pre-TIPS HE was demonstrated with Kaplan-Meier curves. Univariate and multivariate logistic regression analyses were performed to identify the predictors of post-TIPS clinical outcomes for patients with and without pre-TIPS HE. RESULTS: We identified 202 TIPS recipients (61% male, mean ± SD; age 59.1 ± 10.2 years; mean model for end-stage liver disease score 17.3 ± 6.9). Pre-TIPS HE did not predispose patients for increased all-cause mortality, increased risk of experiencing HE within 60 days, or increased risk of hospital admission for HE within 6 months. A multivariate analysis demonstrated that total bilirubin (odds ratio [OR] 1.03; P = 0.016) and blood urea nitrogen (OR 1.15; P = 0.002) were predictors for all-cause mortality within 6 months post-TIPS. Age ≥65 years (OR 3.92; P = 0.004), creatinine (OR 2.22; P = 0.014), and Child-Pugh score (OR 1.53; P = 0.006) were predictors for HE within 60 days post-TIPS. Predictors of intensive care admission for HE within 6 months post-TIPS included age ≥65 years (OR 8.84; P = 0.018), history of any admission for HE within 6 months pre-TIPS (OR 8.42; P = 0.017), and creatinine (OR 2.22; P = 0.015). DISCUSSION: If controlled, pre-TIPS HE does not adversely impact patient survival or clinical outcomes, such as development of HE within 60 days of TIPS or hospital admission for HE within 6 months. Patients may be able to undergo TIPS for refractory ascites despite a history of HE.

Validity and reliability of a short self-efficacy instrument for hypertension treatment adherence among adults with uncontrolled hypertension.

OBJECTIVE: To establish the reliability and validity of a self-report measure designed to assess self-efficacy for hypertension treatment adherence. METHODS: This investigation was embedded within a six-month randomized clinical trial (RCT), which demonstrated that a tailored, stage-matched intervention was more effective at improving hypertension control than usual care among individuals (n = 533) with repeated uncontrolled hypertension. The instrument used to assess self-efficacy for hypertension treatment adherence (SE-HTA) comprised three subscales that assessed diet self-efficacy (DSE), exercise self-efficacy (ESE), and medication self-efficacy (MSE). To determine SE-HTA validity and reliability, we assessed internal consistency using Cronbach's α coefficients, conducted exploratory factor analysis, and evaluated convergent and discriminant validity, as well as test-retest reliability using Spearman's ρ correlation coefficients. RESULTS: Cronbach's α (internal consistency) values for DSE, ESE, and MSE were 0.81, 0.82 and 0.74. Factor analysis and the scree plot demonstrated three distinct factors, which correspond to the three subscales contained in the SE-HTA instrument. SE-HTA possessed good convergent and discriminant validity, and moderate test-retest reliability. CONCLUSION: The SE-HTA instrument containing diet, exercise, and medication adherence subscales is valid and reliable in adults with uncontrolled hypertension. PRACTICE IMPLICATIONS: This SE-HTA instrument measures self-efficacy and could help facilitate behavior change in hypertension.

Contemporary Trends and Comparative Outcomes With Adjunctive Inferior Vena Cava Filter Placement in Patients Undergoing Catheter-Directed Thrombolysis for Deep Vein Thrombosis in the United States: Insights From the National Inpatient Sample.

OBJECTIVES: The aim of this study was to investigate the contemporary trends and comparative effectiveness of adjunctive inferior vena cava filter (IVCF) placement in patients undergoing catheter-directed thrombolysis (CDT) for treatment of proximal lower extremity or caval deep vein thrombosis. BACKGROUND: CDT is being increasingly used in the management of proximal deep vein thrombosis. Although a significant number of patients treated with CDT undergo adjunctive IVCF placement, the benefit of this practice remains unknown. METHODS: The National Inpatient Sample database was used to identify all patients with proximal or caval deep vein thrombosis who underwent CDT (with and without adjunctive IVCF placement) in the United States between January 2005 and December 2013. A propensity score-matching algorithm was then used to derive 2 matched groups of patients (IVCF and no IVCF) for comparative outcomes (mortality and major and minor bleeding) and resource use analysis. RESULTS: Of the 7,119 patients treated with CDT, 2,421 (34%) received IVCFs. There was no significant difference in in-hospital mortality (0.7% vs 1.0%; p = 0.20), procedure-related hemorrhage (1.4% vs. 1.0%; p = 0.23), or intracranial hemorrhage (0.7% vs. 0.6%; p = 0.70) between the IVCF (n = 2,259) and no-IVCF (n = 2,259) groups, respectively. Patients undergoing IVCF placement had higher rates of hematoma (3.4% vs 2.1%; p = 0.009), higher in-hospital charges ($104,049 ± 75,572 vs. $92,881 ± 80,194; p < 0.001) and increased length of stay (7.3 ± 5.6 days vs. 6.9 ± 6.9 days; p = 0.046) compared with the no-IVCF group. CONCLUSIONS: This nationwide observational study suggests that one-third of all patients undergoing CDT receive IVCFs. IVCF use was not associated with a decrease in in-hospital mortality but was associated with higher inpatient charges and longer length of stay.

Zn/CuI-mediated coupling of alkyl halides with vinyl sulfones, vinyl sulfonates, and vinyl sulfonamides.

A novel high-yielding Zn/CuI-mediated coupling method of alkyl halides with vinyl sulfones, vinyl sulfonates, and vinyl sulfonamides is described. This protocol is applicable for primary, secondary, and tertiary alkyl iodides and bromides. Alkyl chlorides and aryl and vinyl halides were unreactive under the reaction conditions. Formamide was found to be a superior solvent for obtaining high yields.

Direct and convenient conversion of alcohols to fluorides.

[reaction: see text] Directly mixing primary, secondary, and tertiary alcohols with nC(4)F(9)SO(2)F-NR(3)(HF)(3)-NR(3) in THF or MeCN results in convenient conversion to the corresponding fluorides in high yields. The readily available reagents are easy to handle, and the mild, almost neutral reaction conditions allow for excellent functional group compatibility. A NR(3)(HF)(3)/NR(3) ratio of

Efficient synthesis of NK(1) receptor antagonist aprepitant using a crystallization-induced diastereoselective transformation.

An efficient stereoselective synthesis of the orally active NK(1) receptor antagonist Aprepitant is described. A direct condensation of N-benzyl ethanolamine with glyoxylic acid yielded a 2-hydroxy-1,4-oxazin-3-one which was activated as the corresponding trifluoroacetate. A Lewis acid mediated coupling with enantiopure (R)-1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-ol afforded a 1:1 mixture of acetal diastereomers which was converted into a single isomer via a novel crystallization-induced asymmetric transformation. The resulting 1,4-oxazin-3-one was converted via a unique and highly stereoselective one-pot process to the desired alpha-(fluorophenyl)morpholine derivative. Interesting and unexpected [1,2]-Wittig and [1,3]-sigmatropic rearrangements were identified during the optimization of these key steps. In the final step, a triazolinone side chain was appended to the morpholine core. The targeted clinical candidate was thus obtained in 55% overall yield over the longest linear sequence.

Practical asymmetric synthesis of aprepitant, a potent human NK-1 receptor antagonist, via a stereoselective Lewis acid-catalyzed trans acetalization reaction.

A streamlined and high-yielding synthesis of aprepitant (1), a potent substance P (SP) receptor antagonist, is described. The enantiopure oxazinone 16 starting material was synthesized via a novel crystallization-induced dynamic resolution process. Conversion of 16 to the penultimate intermediate cis-sec-amine 9 features a highly stereoselective Lewis acid-catalyzed trans acetalization of chiral alcohol 3 with trichloroacetimidate 18 followed by inversion of the adjacent chiral center on the morpholine ring. The six-step process for the synthesis of 9 was accomplished in extremely high overall yield (81%) and with only two isolations.

Pd-catalyzed N-arylation of heteroarylamines.

The palladium-catalyzed N-(hetero)arylation of a number of heteroarylamines including 2-aminopyridines, 2-aminothiazoles, and their analogues has been realized using Xantphos as the ligand. Weak bases such as Cs(2)CO(3), Na(2)CO(3), and K(3)PO(4) were used in most cases to allow for the introduction of functional groups. Choice of the base and solvent was critical for the success of these reactions. [reaction: see text]