Anti-VEGF Pharmaceutical Prior Authorization in Retina Practices.

Importance: Anti-vascular endothelial growth factor (VEGF) intravitreal injections, a mainstay of treatment for many retinal diseases to optimize visual outcomes, have been included in prior authorization (PA) initiatives. However, if clinicians are extremely accurate in their use of anti-VEGF medications, such administrative burdens may need reconsideration. Objective: To quantify PA for anti-VEGF medications (aflibercept, ranibizumab, and bevacizumab) that were approved and determine associated administrative burdens experienced by retina practices. Design, Setting, and Participants: Prospective multicenter quality improvement study conducted from January 2022 through June 2022, and participants were 9 private retina practices across the US. Main Outcomes and Measures: Overall rate of approval of PA requests, reasons for requesting PA, and overall rate of delay of care resulting from PA procedures. Results: In total, 2365 PA requests were recorded, 2225 of which met inclusion criteria. Overall, 2140 (96.2%) requests were approved. The most common reason for requesting PA, at 64% (1423 of 2225 requests), was reauthorization for a previously utilized medication. Of the 2140 approvals, 59.6% (1277) resulted in a delay in care greater than 24 hours, and 40% (863) were given on the date of service. In a granular analysis of a subset of delayed approvals, 23.9% (173 of 725) were approved within 1 day, 15.9% (115 of 725) were approved within 2 to 3 days, 21.5% (156 of 725) were approved within 4 to 7 days, 26.3% (191 of 725) were approved within 8 to 31 days, and 12.4% (90 of 725) were approved within more than 31 days. Overall, PA denial for step therapy was 2.9% (65 of 2225) of requests and uncovered diagnoses was 0.9% (20 of 2225) of requests. The median staff time spent to obtain a single PA was 100 (range, 0-200) minutes. Conclusions and Relevance: In this study, PA requests were almost always approved but led to a delay in patient care in most patients. The current study suggests that the PA process may not be effective for retina specialists if these results can be generalized to other practices in the US and if less burdensome and less costly approaches could result in similar approval rates. Potential short-term solutions may include eliminating the PA process for bevacizumab and reauthorizations for established patients.

Formation of Products of Incomplete Destruction (PID) from the Thermal Oxidative Decomposition of Perfluorooctanoic Acid (PFOA): Measurement, Modeling, and Reaction Pathways.

The thermal decomposition of perfluorooctanoic acid (PFOA) under oxidative conditions was investigated using air (O2) and N2O as oxidants over temperatures ranging from 400 to 1000 °C in an α-alumina reactor. In the presence of air, PFOA was found to decompose into perfluorohept-1-ene (C7F14) and perfluoroheptanoyl fluoride (C7F14O) in addition to HF, CO, and CO2. At temperatures above 800 °C, both C7F14 and C7F14O were no longer detected. A comprehensive analysis of the reaction mechanisms through quantum chemical analysis and kinetic modeling in combination with experimental observations was utilized to identify key reaction pathways. Quantum chemical analysis led to the conclusion that oxygen atoms are crucial in decomposing perfluoroalk-1-enes, especially the stable perfluorohept-1-ene (C7F14). Under oxidative conditions, it was found that significant quantities of C2F6 and CF4 were formed. Further quantum chemical analysis suggests that the O atoms facilitate the formation of volatile fluorinated compounds (VFCs) such as tetrafluoromethane (CF4) and hexafluoroethane (C2F6), particularly at higher temperatures. By elucidating these key reactions, an improved understanding of the potential formation products of incomplete combustion (PICs) or products of incomplete destruction (PIDs) is made.

Clinical outcomes following transtibial medial meniscal root repair are maintained at long-term follow-up.

PURPOSE: To evaluate long-term outcomes of patients treated with posterior medial meniscal root tear (PMMRT) repair through assessment of functional outcome scores and to identify patient surgical and magnetic resonance imaging (MRI) characteristics associated with improved outcomes. METHODS: This was a single-centre, retrospective study evaluating patients who had undergone a PMMR repair using a transtibial suture pullout technique with two locking cinch sutures. This was performed as a follow-up to previously published 2-year and 5-year outcome studies, using the same cohort. All patients from the prior short-term and midterm studies were invited to participate. Patient-reported outcome (PROs) scores, including the International Knee Documentation Committee (IKDC) and Lysholm scores, were collected. Previously collected demographic data were updated based on review of the electronic medical record. Patient outcomes were assessed preoperatively, as well as at 2-year, 5-year and 8-year postoperatively. MRI outcome measurements were assessed at 2-year and 5-year follow-ups. All statistical analysis was performed using SPSS version 26. RESULTS: Seventeen patients of the original 18 patients (94.4%) were included in the final analysis. Additionally, three patients who had additional ipsilateral surgery were excluded from the analysis of PROs. The IKDC score significantly increased from 44.7 ± 11.6 at preoperative baseline to 71.2 ± 21.3 at 8-year post-operation (p = 0.001). There were no significant differences in IKDC score between 2-year and 8-year follow-ups (p = n.s.) or 5-year and 8-year follow-ups (p = n.s.). The Lysholm score significantly increased from 49.6 ± 7.3 at preoperative baseline to 76.4 ± 17.2 at 8-year follow-up (p < 0.001). There was no significant difference in Lysholm scores between 2-year and 8-year follow-ups (p = n.s.) or 5-year and 8-year follow-ups (p = n.s.). A linear regression analysis found that 5-year IKDC scores were significantly correlated with 8-year IKDC scores (ß = 0.681, p = 0.038). At 8-year follow-up, four (23.5%) patients required additional procedures on their operative knee (one total knee arthroplasty conversion). CONCLUSION: Patients treated with repair of PMMRT had maintenance of clinical outcome improvements at long-term follow-up despite worsening MRI outcomes at short-term and medium-term follow-ups. While a high proportion of patients required additional procedures on their operative knee at 8-year follow-up, few of these patient's additional procedures were related to failure of their primary surgery. Providers and patients may expect durable clinical outcomes following the repair of PMMRT, irrespective of radiographic appearance. LEVEL OF EVIDENCE: Level IV.

Mitigating Cobalt Phthalocyanine Aggregation in Electrocatalyst Films through Codeposition with an Axially Coordinating Polymer.

Cobalt phthalocyanine (CoPc) is a promising molecular catalyst for aqueous electroreduction of CO2, but its catalytic activity is limited by aggregation at high loadings. Codeposition of CoPc onto electrode surfaces with the coordinating polymer poly(4-vinylpyridine) (P4VP) mitigates aggregation in addition to providing other catalytic enhancements. Transmission and diffuse reflectance UV-vis measurements demonstrate that a combination of axial coordination and π-stacking effects from pyridyl moieties in P4VP serve to disperse cobalt phthalocyanine in deposition solutions and help prevent reaggregation in deposited films. Polymers lacking axial coordination, such as Nafion, are significantly less effective at cobalt phthalocyanine dispersion in both the deposition solution and in the deposited films. SEM images corroborate these findings through particle counts and morphological analysis. Electrochemical measurements show that CoPc codeposited with P4VPonto carbon electrode surfaces reduces CO2 with higher activity and selectivity compared to the catalyst codeposited with Nafion.

Germ Cell Tumor of the Testis: Lethal Subtypes of a Curable Cancer.

Germ cell tumor of the testis (GCT) is a curable cancer even when it is widely metastatic; however, outcomes can differ based on tumor histology. Chemo-resistance in certain phenotypes, such as teratoma and yolk sac tumor, contributes to poor clinical outcomes in some patients with GCT. Despite this resistance to S-YSTemic therapy, many of these tumor subtypes remain amenable to surgical resection and possible cure. In this study, we report on a series of seven patients highlighting two chemo-resistant subtypes of nonseminomatous germ cell tumor (NSGCT), sarcomatoid yolk sac tumor (S-YST), and epithelioid trophoblastic tumor (ETT) for which early resection rather than additional salvage chemotherapy or high-dose intense chemotherapy might provide a superior clinical outcome and enhance cure rate.

Automated detection of early signs of irreversible ischemic change on CTA source images in patients with large vessel occlusion.

PURPOSE: To create and validate an automated pipeline for detection of early signs of irreversible ischemic change from admission CTA in patients with large vessel occlusion (LVO) stroke. METHODS: We retrospectively included 368 patients for training and 143 for external validation. All patients had anterior circulation LVO stroke, endovascular therapy with successful reperfusion, and follow-up diffusion-weighted imaging (DWI). We devised a pipeline to automatically segment Alberta Stroke Program Early CT Score (ASPECTS) regions and extracted their relative Hounsfield unit (rHU) values. We determined the optimal rHU cut points for prediction of final infarction in each ASPECT region, performed 10-fold cross-validation in the training set, and measured the performance via external validation in patients from another institute. We compared the model with an expert neuroradiologist for prediction of final infarct volume and poor functional outcome. RESULTS: We achieved a mean area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity of 0.69±0.13, 0.69±0.09, 0.61±0.23, and 0.72±0.11 across all regions and folds in cross-validation. In the external validation cohort, we achieved a median [interquartile] AUC, accuracy, sensitivity, and specificity of 0.71 [0.68-0.72], 0.70 [0.68-0.73], 0.55 [0.50-0.63], and 0.74 [0.73-0.77], respectively. The rHU-based ASPECTS showed significant correlation with DWI-based ASPECTS (rS = 0.39, p<0.001) and final infarct volume (rS = -0.36, p<0.001). The AUC for predicting poor functional outcome was 0.66 (95%CI: 0.57-0.75). The predictive capabilities of rHU-based ASPECTS were not significantly different from the neuroradiologist's visual ASPECTS for either final infarct volume or functional outcome. CONCLUSIONS: Our study demonstrates the feasibility of an automated pipeline and predictive model based on relative HU attenuation of ASPECTS regions on baseline CTA and its non-inferior performance in predicting final infarction on post-stroke DWI compared to an expert human reader.

Comparing Outcomes of Post-Cardiotomy Cardiogenic Shock Patients: On-Site Cannulation vs. Retrieval for V-A ECMO Support.

Background: Post-cardiotomy cardiogenic shock (PCCS) remains a life-threatening complication after cardiac surgery. Extracorporeal membrane oxygenation (ECMO) represents the mainstay of mechanical circulatory support for PCCS; however, its availability is limited to larger experienced centers, leading to a mismatch between centers performing cardiac surgery and hospitals offering ECMO management beyond cannulation. We sought to evaluate the outcomes and complications of PCCS patients requiring veno-arterial (V-A) ECMO cannulated at our hospital compared to those cannulated at referral hospitals. Methods: A retrospective analysis of PCCS patients requiring V-A ECMO was conducted between October 2014 to December 2022. Results: A total of 121 PCCS patients required V-A ECMO support, of which 62 (51%) patients were cannulated at the referring institutions and retrieved (retrieved group), and 59 (49%) were cannulated at our hospital (on-site group). The baseline demographics and pre-ECMO variables were similar between groups, except retrieved patients had higher lactic acid levels (retrieved group: 8.5 mmol/L ± 5.8 vs. on-site group: 6.6 ± 5; p = 0.04). Coronary artery bypass graft was the most common surgical intervention (51% in the retrieved group vs. 47% in the on-site group). There was no difference in survival-to-discharge rates between the groups (45% in the retrieved group vs. 51% in the on-site group; p = 0.53) or in the rate of patient-related complications. Conclusions: PCCS patients retrieved on V-A ECMO can achieve similar outcomes as those cannulated at experienced centers. An established network in a hub-and-spoke model is critical for the PCCS patients managed at hospitals without ECMO abilities to improve outcomes.

Analysis of plant and fungal transcripts from resistant and susceptible phenotypes of Leptospermum scoparium challenged by Austropuccinia psidii.

Austropuccinia psidii is the causal pathogen of myrtle rust disease of Myrtaceae. To gain understanding of the initial infection process, gene expression in germinating Austropuccinia psidii urediniospores and in Leptospermum scoparium inoculated leaves were investigated via analyses of RNAseq samples taken 24 and 48 hours post inoculation (hpi). Principal component analyses of transformed transcript count data revealed differential gene expression between the uninoculated L. scoparium control plants that correlated with the three plant leaf resistance phenotypes (immunity, hypersensitive response and susceptibility). Gene expression in the immune resistant plants did not significantly change in response to fungal inoculation, while susceptible plants showed differential expression of genes in response to fungal challenge. A putative disease resistance gene, jg24539.t1, was identified in the L. scoparium hypersensitive response phenotype family. Expression of this gene may be associated with the phenotype and could be important for further understanding the plant hypersensitive response to A. psidii challenge. Differential expression of pathogen genes was found between samples taken 24 and 48 hpi, but there were no significant differences in pathogen gene expression that were associated with the three different plant leaf resistance phenotypes. There was a significant decrease in the abundance of fungal transcripts encoding three putative effectors and a putative carbohydrate-active enzyme between 24 and 48 hpi, suggesting that the encoded proteins are important during the initial phase of infection. These transcripts, or their translated proteins, may be potential targets to impede the early phases of fungal infection by this wide-host range obligate biotrophic basidiomycete.

Building a Culture of Health Through the Built Environment: Impact of a Cluster Randomized Trial Remediating Vacant and Abandoned Property on Health Mindsets.

Changing built environment conditions to impact health mindsets and health equity may be a promising target for public health interventions. The present study was a cluster randomized controlled trial to test the impact of remediating vacant and abandoned properties on factors related to health mindset-including well-being, health interconnectedness, social capital markers, neighborhood disorder and worry-as well as direct and indirect violence experiences and the moderating role of racial and income segregation on outcomes. A residential cohort of 405 participants from 194 randomly assigned geographic clusters were surveyed over five waves from 2019 to 2023. Compared to clusters with no treatment, participants in clusters where both vacant lots and abandoned homes were treated experienced significant increases in sense of community (83%, 95% CI=71 to 96%, p=0.01). Among participants in randomization clusters where only vacant lots were treated, there were declines in perceived neighborhood disorder (-55%, 95% CI=-79 to -5, p=0.06) and worry about community violence (-56%, 95% CI=-58 to - 12, p=0.06). There was also a moderating effect of racial and income spatial polarization, with the greatest changes in sense of community observed among more deprived areas with both homes and lots treated; and the largest changes in neighborhood worry and disorder were seen in more deprived areas with only lots treated. Remediation of vacant and abandoned properties may be one approach to change some but not all mindsets around health, and the effects may depend on the type of remediation as well as larger neighborhood conditions such segregation.

Lower Pregnancy and Live Birth Rates with Vaginal Endometrin Plus Intramuscular Progesterone Every Third Day Versus Intramuscular Progesterone Alone in Programmed Frozen Embryo Transfers: A Retrospective Case-control Study.

This study aimed to determine whether the use of vaginal Endometrin plus intramuscular progesterone on every third day (VIM) in programmed frozen embryo transfer (FET) is associated with lower pregnancy and live birth rates compared to daily intramuscular progesterone (IM). FET data from a single program were collected between November 2018 and December 2021. A total of 903 FETs were analyzed, including 504 FETs in the IM group, and 399 FETs in the VIM group. Inclusion criteria were women undergoing FETs with either 50 mg daily IM progesterone only (control) or 200 mg Endometrin twice daily plus 50 mg IM progesterone on every third day, with the transfer of a single day 5 or 6 frozen embryo. There were no significant differences in patient age at time of FETs, BMI, endometrial thickness, blastocyst quality, or infertility diagnosis between the groups. The VIM had significantly lower positive hCG and clinical pregnancy rates compared to the IM (60.2% vs 72.0% and 40.6% vs 56.7%, respectively, P = 0.0002 and P < 0.0001). The live birth rate was 36.1% in the VIM, compared to 49.4% in the IM (P < 0.0001). These findings also remained significant when excluding FETs with donor egg (35.9% vs 50.1%, P < 0.0001). This study demonstrated that VIM in FET cycles yields significantly lower pregnancy and live birth rates compared to IM along. IM progesterone alone may be preferable to combined Endometrin and IM progesterone in patients undergoing programmed frozen embryo transfers.

Combined Medial Collateral Ligament Reconstruction and Polyethylene Exchange for Valgus Instability Following Total Knee Arthroplasty.

Valgus instability can occur after total knee arthroplasty (TKA) due to traumatic medial collateral ligament (MCL) injury, component malpositioning, or progressive ligamentous laxity. Although revision TKA with exchange of the polyethylene to a varus-valgus-constrained liner can reduce laxity due to MCL insufficiency, isolated liner exchange in the setting of collateral ligament insufficiency may lead to greater strain at the cement-bone or implant-cement interface and possibly a greater rate of aseptic loosening. Anatomic MCL reconstruction can be performed in conjunction with liner exchange to restore stability and reduce strain compared with liner exchange alone. The purpose of this Technical Note is to describe a technique for MCL reconstruction and liner exchange for treatment of valgus instability after TKA.

Diagnostic accuracy of upper tract urothelial carcinoma using biopsy, urinary cytology, and nephroureterectomy specimens: A tertiary cancer center experience.

OBJECTIVES: We studied the diagnostic accuracy and discordance of upper tract urothelial carcinoma (UTUC) by comparing biopsy and urinary cytology with matched nephroureterectomy specimens. METHODS: Sixty-nine patients with UTUC without neoadjuvant treatment were retrospectively identified who had matched biopsy and nephroureterectomy specimens. Twenty patients had concurrent upper tract cytology. H&E and cytology slides were re-reviewed. Statistical analysis was performed. RESULTS: Patients included 48 men and 21 women with a mean age of 69 years. A concordant grade between biopsy and surgical specimen was present in 49 (71%) patients. The mean size of biopsy specimens in the discordant group was significantly smaller than that in the concordant group. Invasion was evaluated in 48 biopsy cases that had adequate subepithelial tissue, and 33 of them were diagnosed with concordant invasion status. Mean tumor size in both tumor grade and invasion discordant groups was significantly larger than that in the concordant group. High-grade urothelial carcinoma was detected in 84% of cases using urinary cytology. CONCLUSIONS: Our study demonstrates the diagnostic challenges of UTUC on small biopsy specimens. Biopsy specimen size and tumor size are significantly associated with the diagnostic discordance. Upper tract cytology showed high diagnostic accuracy and should be complementary to the biopsy.

Re-thinking all-cause COVID-19 hospitalizations as a surrogate measure for severe illness in observational surveillance studies.

All-cause COVID-19 hospitalization ≤ 30 days of infection is a common outcome for severe illness in observational/surveillance studies. Milder COVID-19 disease and COVID-19-specific measurements calls for an evaluation of this endpoint. This was a descriptive, retrospective cohort study of adults ≥ 18 who were established in primary care at Veteran Health Administration (VHA) facilities. The outcome was hospitalization within 30 days of a laboratory-confirmed, symptomatic SARS-CoV-2 infection. Between December 15, 2021 and May 1, 2022, a simple random sample of all VA facilities, excluding Puerto Rico or Philippines, was drawn to identify these hospitalized cases and determine whether hospitalization was due to COVID-19-specific causes. A chart review was conducted to record the inpatient clinical team's diagnosis and whether the inpatient team classified the diagnosis as COVID-19 related or not. These data were used to classify hospitalizations as either due to COVID-19-specific causes (direct manifestations of SARS-CoV-2 infection) or non-COVID-19-specific hospitalizations (incidental SARS-CoV-2 infection), A simple random sample of 9966 (12.3%) all-cause hospitalizations (95% CI: 12.1%, 12.5%) was used to select 300 representative patients. Of these, 226/300 (75.3%) were determined to be COVID-19-specific. COVID-19 pneumonia was most common (147/226, 65.0%). The highest proportion of COVID-19-specific hospitalizations occurred among unvaccinated (85.0%), followed by vaccinated but not boosted (73.7%) and boosted (59.4%) (p < 0.001). The proportion of non-COVID-19-specific hospitalizations was higher in the later period (15-30 days: 55.0%) than the early (0-15 days: 22.5%) (p = 0.003). This study supports the outcome of COVID-19-specific hospitalization instead of all-cause hospitalization in observational studies. The earlier outcome period (0-15 days) was less susceptible to potential measurement bias.

Suppressed basal mitophagy drives cellular aging phenotypes that can be reversed by a p62-targeting small molecule.

Selective degradation of damaged mitochondria by autophagy (mitophagy) is proposed to play an important role in cellular homeostasis. However, the molecular mechanisms and the requirement of mitochondrial quality control by mitophagy for cellular physiology are poorly understood. Here, we demonstrated that primary human cells maintain highly active basal mitophagy initiated by mitochondrial superoxide signaling. Mitophagy was found to be mediated by PINK1/Parkin-dependent pathway involving p62 as a selective autophagy receptor (SAR). Importantly, this pathway was suppressed upon the induction of cellular senescence and in naturally aged cells, leading to a robust shutdown of mitophagy. Inhibition of mitophagy in proliferating cells was sufficient to trigger the senescence program, while reactivation of mitophagy was necessary for the anti-senescence effects of NAD precursors or rapamycin. Furthermore, reactivation of mitophagy by a p62-targeting small molecule rescued markers of cellular aging, which establishes mitochondrial quality control as a promising target for anti-aging interventions.

Stacking Fault-Enriched MoNi4/MoO2 Enables High-Performance Hydrogen Evolution.

Producing green hydrogen in a cost-competitive manner via water electrolysis will make the long-held dream of hydrogen economy a reality. Although platinum (Pt)-based catalysts show good performance toward hydrogen evolution reaction (HER), the high cost and scarce abundance challenge their economic viability and sustainability. Here, a non-Pt, high-performance electrocatalyst for HER achieved by engineering high fractions of stacking fault (SF) defects for MoNi4/MoO2 nanosheets (d-MoNi) through a combined chemical and thermal reduction strategy is shown. The d-MoNi catalyst offers ultralow overpotentials of 78 and 121 mV for HER at current densities of 500 and 1000 mA cm-2 in 1 M KOH, respectively. The defect-rich d-MoNi exhibits four times higher turnover frequency than the benchmark 20% Pt/C, together with its excellent durability (> 100 h), making it one of the best-performing non-Pt catalysts for HER. The experimental and theoretical results reveal that the abundant SFs in d-MoNi induce a compressive strain, decreasing the proton adsorption energy and promoting the associated combination of *H into hydrogen and molecular hydrogen desorption, enhancing the HER performance. This work provides a new synthetic route to engineer defective metal and metal alloy electrocatalysts for emerging electrochemical energy conversion and storage applications.

MANAGEMENT OF LARGE FULL-THICKNESS MACULAR HOLES: Long-Term Outcomes of Internal Limiting Membrane Flaps and Internal Limiting Membrane Peels.

BACKGROUND/PURPOSE: To determine and compare the efficacy of a surgical internal limiting membrane (ILM) flap technique with the traditional ILM peel on long-term visual and anatomical outcomes for large (>400 µm) full-thickness macular holes. METHODS: From October 2016 to July 2022, patients undergoing initial full-thickness macular hole repair with the ILM flap or ILM peel technique were reviewed. Final outcomes were recorded and based on size in microns: 401 to 800, 801 to 1,200, and >1,200. RESULTS: Patients treated with ILM flap (n = 52, 94.2% closure rate) or ILM peel (n = 407, 93.6% closure rate) were followed with a mean follow-up time of 15.0 ± 10.2 and 20.0 ± 13.4 months, respectively. Success rates for ILM flaps and ILM peels were compared for full-thickness macular holes of 401 to 800 (100%, 95.8%, P = 0.39), 801 to 1,200 (95%, 93%, P = 0.74), and >1,200 (86.7%, 86.7%, P = 1.0) µm. Mean best-recorded logarithm of the minimal angle of resolution visual acuity for ILM flaps and ILM peels, respectively, was 1.02 ± 0.46 and 0.87 ± 0.47 preoperatively, with follow-up acuity of 0.48 ± 0.32 (P < 0.03) and 0.39 ± 0.42 (P < 0.01) at Year 3. CONCLUSION: Both techniques provide a similar anatomical closure rate and functional improvement in vision. Comparisons should be cautiously made based on difference in preoperative hole size.

Primary pure squamous cell carcinoma of the gallbladder.

SummarySquamous cell carcinoma (SCC) is an uncommon and frequently aggressive subtype of gallbladder cancer known for its poor outcomes compared with other gallbladder tumours. Gallbladder SCC typically presents as higher grade and more advanced than adenocarcinoma, resulting in lower estimated survival. Early recognition of these tumours is ideal, but infrequently achieved. Herein is a case of a male patient in his 80s with new onset abdominal pain who was initially diagnosed with cholecystitis, but diagnostic imaging revealed a gallbladder mass. Surgical resection and pathology revealed pure SCC of the gallbladder without local organ invasion or metastatic disease. Pure SCC histology of the gallbladder is rare, with limited studies on clinical presentation, natural history, and optimal treatment.

Sequenced treatment effectiveness for posttraumatic stress (STEPS) trial: A protocol for a pragmatic comparative effectiveness trial with baseline results.

BACKGROUND: There have only been two efficacy trials reporting a head-to-head comparison of medications and psychotherapy for posttraumatic stress disorder (PTSD), and neither was conducted in primary care. Therefore, in this pragmatic trial we compare outcomes of primary care patients randomized to initially receive a brief trauma-focused psychotherapy or a choice of three antidepressants. In addition, because there are few trials examining the effectiveness of subsequent treatments for patients not responding to the initial treatment, we also compare the outcomes of those switching or augmenting treatments. METHOD: Patients screening positive for PTSD (n = 700) were recruited from the primary care clinics of 7 Federally Qualified Health Centers (FQHC) and 8 Department of Veterans Affairs (VA) Medical Centers and randomized in the ratio 1:1:2 to one of three treatment sequences: 1) selective serotonin reuptake inhibitor (SSRI) followed by augmentation with Written Exposure Therapy (WET), 2) SSRI followed by a switch to serotonin-norepinephrine reuptake inhibitor (SNRI), or 3) WET followed by a switch to SSRI. Participants complete surveys at baseline, 6 months, and 12 months. The primary outcome is PTSD symptom severity as measured by the PTSD Checklist (PCL-5). RESULTS: The average PCL-5 score was 52.8 (SD = 11.1), indicating considerable severity. The most common bothersome traumatic event for VA enrollees was combat (47.8%), and for FQHC enrollees was other (28.2%), followed by sexual assault (23.4%), and child abuse (19.8%). Only 22.4% were taking an antidepressant at baseline. CONCLUSION: Results will help healthcare systems and clinicians make decisions about which treatments to offer to patients. CLINICALTRIALS: govID - NCT04597190.

Using Electronic Health Record Data to Determine the Safety of Aqueous Humor Liquid Biopsies for Molecular Analyses.

Purpose: Knowing the surgical safety of anterior chamber liquid biopsies will support the increased use of proteomics and other molecular analyses to better understand disease mechanisms and therapeutic responses in patients and clinical trials. Manual review of operative notes from different surgeons and procedures in electronic health records (EHRs) is cumbersome, but free-text software tools could facilitate efficient searches. Design: Retrospective case series. Participants: A total of 1418 aqueous humor liquid biopsies from patients undergoing intraocular surgery. Methods: Free-text EHR searches were performed using the Stanford Research Repository cohort discovery tool to identify complications associated with anterior chamber paracentesis and subsequent endophthalmitis. Complications of the surgery unrelated to the biopsy were not reviewed. Main Outcome Measures: Biopsy-associated intraoperative complications and endophthalmitis. Results: A total of 1418 aqueous humor liquid biopsies were performed by 17 experienced surgeons. EHR free-text searches were 100% error-free for surgical complications, >99% for endophthalmitis (<1% false positive), and >93.6% for anesthesia type, requiring manual review for only a limited number of cases. More than 85% of cases were performed under local anesthesia without ocular muscle akinesia. Although the most common indication was cataract (50.1%), other diagnoses included glaucoma, diabetic retinopathy, uveitis, age-related macular degeneration, endophthalmitis, retinitis pigmentosa, and uveal melanoma. A 50- to 100-µL sample was collected in all cases using either a 30-gauge needle or a blunt cannula via a paracentesis. The median follow-up was >7 months. There was only one minor complication (0.07%) identified: a case of a small tear in Descemet membrane without long-term sequelae. No other complications occurred, including other corneal injuries, lens or iris trauma, hyphema, or suprachoroidal hemorrhage. There was no case of postoperative endophthalmitis. Conclusions: Anterior chamber liquid biopsy during intraocular surgery is a safe procedure and may be considered for large-scale collection of aqueous humor samples for molecular analyses. Free-text EHR searches are an efficient approach to reviewing intraoperative procedures. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Hepatitis B transmission/reactivation associated with Hepatitis B core antibody and Hepatitis C nucleic acid testing positive organs: A report from the Organ Procurement and Transplantation Network Disease Transmission Advisory Committee.

BACKGROUND: Better access to direct-acting antiviral (DAA) therapy has broadened the utilization of hepatitis C virus (HCV) nucleic acid testing (NAT) positive organs with excellent outcomes. However, DAA therapy has been associated with hepatitis B virus (HBV) reactivation. AIM: To determine the risk of HBV transmission or reactivation with utilization of HBV core antibody positive (HBcAb+) and HCV NAT positive (HCV+) organs, which presumably required DAA therapy. METHODS: The number of HBcAb+ donors with delineated HCV NAT status was obtained from the Organ Procurement and Transplantation Network (OPTN) database. The number of unexpected HBV infections from transplanted organs adjudicated as "proven" or "probable" transmission was obtained from the OPTN Ad Hoc Disease Transmission Advisory Committee database. A chart review of the donors of "proven" or "probable" cases was conducted. RESULTS: From January 1, 2016, to December 31, 2021, 7735 organs were procured from 3767 HBcAb+ donors and transplanted into 7469 recipients; 545 (14.5%) donors were also HCV+. HBV transmission or reactivation occurred in seven recipients. The rate is not significantly different between recipients of HCV+ (0.18%, 2/1115) and the HCV NAT negative (HCV-) organs (0.08%, 5/6354) (p = 0.28) or between recipients of HCV+ and HCV- livers as well as non-liver organs. HBV transmission or reactivation occurred within a median of 319 (range, 41-1117) days post-transplant in the setting of missing, inadequate, or truncated prophylaxis. CONCLUSION: HBV reactivation associated with DAA therapy for HBcAb+ HCV+ organs is less frequent than reported in the non-transplant population, possibly due to the common use of HBV prophylaxis in the at-risk transplant population.