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Men who have sex with men (MSM) with HIV are at high risk for squamous intraepithelial lesion (SIL) and anal cancer. The identification of local immunological mechanisms involved in the development of anal dysplasia could aid treatment and diagnostics. We performed a study of 111 anal biopsies obtained from 101 MSM with HIV, who participated in an anal screening program. In a test prospective cohort (N=54), in addition to histological examination, we assessed multiple immune subsets by flow cytometry. Selected molecules were further evaluated by immunohistochemistry in a validation retrospective cohort (N=47). Pathological samples were characterized by the presence of Resident Memory T cells with low expression of CD103 and by changes in the Natural Killer cell subsets, affecting residency and activation. Furthermore, potentially immune suppressive subsets, including CD15+ CD16+ mature neutrophils, gradually increased as the anal lesion progressed. Immunohistochemistry confirmed the association between the presence of CD15 in the epithelium and SIL diagnosis, with a sensitivity of 80% and specificity of 71% (AUC 0.762) for the correlation with high-grade SIL. A complex immunological environment with imbalanced proportions of resident effectors and immune suppressive subsets characterizes pathological samples. Neutrophil infiltration, determined by CD15 staining, may represent a valuable pathological marker associated with the grade of dysplasia.

Background The human immunodeficiency virus (HIV) has caused a lot of havoc since the early 1970s, affecting 37.6 million people worldwide. The 90-90-90 treatment policy was adopted in Ghana in 2015 with the overall aim to end new infections by 2030, and to improve the life expectancy of HIV seropositive individuals. With the scale-up of Highly Active Antiretroviral Therapy (HAART), the lifespan of People Living with HIV (PLWH) on antiretrovirals (ARVs) is expected to improve. In rural districts in Ghana, little is known about the survival probabilities of PLWH on ARVs hence, this study was conducted to estimate the survival trends of PLWH on ARVs for the periods between 2016 to 2020. Methods A retrospective evaluation of data gathered across ARV centers within Tatale and Zabzugu districts in Ghana from 2016 to 2020 among PLWH on ARVs. The census technique was employed and a total of 261 participants were recruited for the study. The data was analyzed using STATA software version 16.0. Lifetable analysis and Kaplan-Meier graph were used to assess the survival probabilities. "Stptime" per 1000 person-years and the competing risk regression was used to evaluate mortality rates and risk of mortality. Results The cumulative survival probability was 0.8847 (95% CI: 0.8334-0.9209). The overall mortality rate was 51.89 (95% CI: 36.89-72.97) per 1000 person-years. WHO stage III and IV [AHR: 4.25 (95%CI: 1.6-9.71) p = 0.001] as well as age group (50+ years) [AHR: 5.02 (95% CI: 1.78-14.13) p=0.002] were associated with mortality. Conclusion Survival probabilities is high among the population of PLWH in Ghana with declining mortality rates. Clinicians should provide critical attention and care to patients at HIV WHO stages III and IV and intensify HIV screening at all entry points since early diagnosis is associated with high survival probabilities.

Importance: Following the repeal of nonmedical vaccine exemption options from school entry immunization laws in California, gains in vaccine coverage were partially offset by increases in medical vaccine exemptions. Although several U.S. states, including New York State (NYS), recently adopted similar legislation, the impact of these laws on school vaccine coverage and medical vaccine exemptions has not yet been examined. Objective: To estimate the effects of NYS legislation eliminating nonmedical school entry vaccine exemptions on required vaccine coverage and the uptake of medical vaccine exemptions at NYS schools outside of New York City (NYC). Design: Interrupted time-series analyses using generalized estimating equations to examine longitudinal school immunization compliance data from the 2012-13 through 2021-22 school years. Setting: New York State public and nonpublic schools outside of NYC. Participants: Schools that submitted [≥] 1 compliance report in the time periods before and after the legislative repeal of nonmedical exemptions with publicly available student enrollment data. Exposure: NYS Senate Bill 2994A was passed in June 2019, eliminating school entry nonmedical vaccine exemptions; since compliance with the law was evaluated for most students during the following school year, we considered the 2019-20 school year as the law's effective date. Main Outcomes and Measures: Main outcomes examined were school required vaccine coverage, defined as the percentage of students at each school who completed all grade-appropriate NYS vaccine requirements, and the percentage of students with a medical vaccine exemption. Results: Among 3,525 eligible schools, the implementation of NYS Senate Bill 2994A was associated with an increase in mean required vaccine coverage of 5% and 1% among nonpublic and public schools, respectively, with additional annual increases in coverage observed through the 2021-22 school year. The law's implementation was also associated with a 0.1% (95% CI: 0.0%, 0.1%) decrease in medical vaccine exemptions at both public and nonpublic schools, and small, but significant mean annual declines in medical vaccine exemptions through the end of the study period. Conclusion and Relevance: The NYS elimination of school entry nonmedical vaccine exemption options was effective to improve required vaccine coverage; coverage gains were not replaced by increases in medical vaccine exemptions.

Objective: We assessed the impact of preexisting dementia on in-hospital mortality, home discharge and complications of Chinese patients with intracerebral hemorrhage (ICH). Methods: Consecutive in-hospital data were extracted from the China Stroke Center Alliance database from August 2015 to July 2019. Patient characteristics, in-hospital mortality, and complications were compared between ICH patients with and without preexisting dementia. Results: Out of the eligible 72,318 patients with ICH, we identified 328 patients with pre-existing dementia. Compared with patients without dementia, those in the dementia group were older, more females and a higher proportion of individuals with lower education, and a history of diabetes, myocardial infarction, stroke, heart failure, peripheral vascular disease and cigarette smoking. Those with pre-existing dementia group were more prone to a greater stroke severity as measured by the National Institute of Health Stroke Scale (NIHSS) and Glasgow Coma Scale (GCS) at presentation. In the adjusted models, the presence of preexisting dementia was associated with an increased risk of in-hospital mortality (OR 2.31, 95% CI 1.12-4.77) and more frequent in-hospital complications of pulmonary embolism (OR 5.41, 95% CI 1.16-25.14), pneumonia (OR 1.58, 95% CI 1.08-2.33), urinary tract infection (OR 2.37; 95% CI 1.21-4.64), and gastrointestinal bleeding (OR 2.39, 95% CI 1.27-4.49). Conclusions:ICH patients with pre-existing dementia are more prone to more severe strokes and poorer outcomes. Future studies should evaluate the value of intensive risk factor control among individuals with pre-existing dementia for stroke prevention.

Heritability of common eye diseases and ocular traits are relatively high. Here, we develop an automated algorithm to detect genetic relatedness from color fundus photographs (FPs). We estimated the degree of shared ancestry amongst individuals in the UK Biobank using KING software. A convolutional Siamese neural network-based algorithm was trained to output a measure of genetic relatedness using 7224 pairs (3612 related and 3612 unrelated) of FPs. The model achieved high performance for prediction of genetic relatedness; when computed Euclidean distances were used to determine probability of relatedness, the area under the receiver operating characteristic curve (AUROC) for identifying related FPs reached 0.926. We performed external validation of our model using FPs from the LIFE-Adult study and achieved an AUROC of 0.69. An occlusion map indicates that the optic nerve and its surrounding area may be the most predictive of genetic relatedness. We demonstrate that genetic relatedness can be captured from FP features. This approach may be used to uncover novel biomarkers for common ocular diseases.

Background: Uterine sarcoma (US) is a highly malignant cancer with poor prognosis and high mortality in women. In this study, we evaluated the expression of human fibroblast growth factor 23 (FGF23) in different US subtypes and the relationship between survival and clinicopathological characteristics. Methods: We conducted a comparative analysis of FGF23 gene expression in different pathological types of US. Utilizing a cohort from The Cancer Genome Atlas (TCGA) of 57 patients, a 50-patient microarray dataset (GSE119043) from the Gene Expression Omnibus (GEO) and a clinical cohort of 44 patients, we analyzed gene expression profiles and corresponding clinicopathological information. Immunohistochemistry (IHC) was used to examine the expression level of FGF23 in four US subtypes. Survival analysis was used to assess the relationship between FGF23 expression and prognosis in US patients. Results: Compared with uterine normal smooth muscle (UNSM) and uterine leiomyoma (ULM), FGF23 expression was significantly upregulated in US and was differentially expressed in four US subtypes. Uterine carcinosarcoma (UCS) exhibited the highest expression of FGF23 among the subtypes. Survival analysis indicated that FGF23 expression was unrelated to overall survival and progression-free survival in US (P>0.05). Similar results were obtained from the validation cohorts. Univariate and multivariate analyses showed no significant correlation between FGF23 expression and the US prognosis. Tumor stage, CA125 and tumor recurrence were independent prognostic factors for survival of US patients. Conclusion: FGF23 was highly expressed in uterine sarcoma and was promising as a novel potential biomarker for the diagnosis and prognosis of uterine sarcoma. Keywords: Human fibroblast growth factor 23, Prognosis, Uterine sarcoma, Biomarker

Background. We discovered a novel finding of ribbon-like signal hyperintensity of the cerebral cortical gyri, named the ribbon sign, after reperfusion therapy. Herein, we report the significance and clinical characteristics of ribbon signs. Methods. Data from consecutive patients with acute ischemic stroke and anterior large-vessel occlusion were prospectively extracted from the Tokushima University Hospital Stroke Registry between January 2011 and March 2020. Diffusion-weighted imaging (DWI) was retrospectively assessed in patients with acute ischemic stroke with large-vessel occlusion, with or without treatment. Results. A total of 140 patients (78 males, Average age: 75.7 years) were enrolled in the study. The mean DWI-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) was 7.0. Among the patients, 113 (80.7%) underwent reperfusion therapy and 95 (67.9%) had unfavorable outcomes. Eighty-one (57.9%) patients underwent successful recanalization. The ribbon sign was more common in patients with successful recanalization than in the patients with unsuccessful recanalization (53.1% vs. 8.5%, respectively; p<0.01). Conclusion. Our study is the first to report that the ribbon sign is a specific finding after successful recanalization in patients with acute ischemic stroke.

Background: Medical education has promoted the rapid interpretation of the arterial blood gas (ABG) as a crucial skill in the management of critically ill patients. The first step of many algorithms focuses on using log-linear estimates to determine the internal consistency of ABG values. However, because of modern computing advances, these estimates are no longer necessary. We propose an alternative method for ascertaining internal consistency of ABG values based on direct calculation derived directly from Henderson-Hasselbach and demonstrate its efficiency and accuracy. Methods: Deidentified ABG values were collected from electronic medical records for the month of September 2022. Estimated hydrogen concentration was calculated by log linear estimation and by the proposed method of direct calculation. Time of computation, a measure of efficiency, was also recorded. Results: Of the 1008 ABGs used for analysis, 185 (18.4%) had estimated hydrogen concentrations that were greater than a 5% threshold according to the guidelines method, suggesting potential internal inconsistency. However, only 13 (1.3%) had estimated hydrogen concentrations greater than 5% by direct calculation. Analysis was also performed at a 10% threshold. On further analysis, 4 ABGs that were identified by the guidelines method as being internally inconsistent, but not identified by the direct calculation method, were found to have pH <7.0, outside the range provided for the current guidelines for log-linear estimation, and were thus incorrectly identified by the guidelines method as being internally inconsistent. The time of computation for direct calculation was approximately 8-fold faster, although the total time of calculation for this dataset was minimal. Conclusions: This study proposes a direct calculation method as an alternative approach to traditional guidelines to assess internal ABG value consistency, the first step of ABG interpretation. We demonstrate that direct calculation is more accurate, identifying less potentially internally inconsistent values, notably at extremes in pH. In addition, the direct calculation algorithm is 8-fold more efficient than guidelines-based algorithm, although actual processing times were miniscule for the data set regardless of the method used. Furthermore, with modern calculators and computers, the direct calculation method is easier to understand and implement than the guideline based approach. Therefore, based on the results of this study, we propose the use of direct calculation as an alternative to log-linear based estimation for the assessment of internal consistency of ABGs.

Background: Decompressive craniectomy (DC) remains a controversial intervention for established or anticipated intracranial hypertension among patients with aneurysmal subarachnoid haemorrhage (aSAH). Methods: We identified aSAH patients who underwent DC following microsurgical aneurysm repair from a prospectively maintained cerebrovascular registry and compared their outcomes with a propensity-matched cohort who did not. Logistic regression was used to identify predictors of undergoing decompressive surgery and post-operative outcome. The outcomes of interest were inpatient mortality, unfavourable outcome at first and final follow-up, NIS-Subarachnoid Hemorrhage Outcome Measure and modified Rankin Score (mRS) at first and final follow-up. Results: A total of 246 consecutive patients with aSAH underwent microsurgical clipping of the culprit aneurysm between 01/09/2011 and 20/07/2020. Of these, 46 patients underwent DC and were included in the final analysis. Unsurprisingly, patients treated with DC had a greater chance of unfavourable outcome (p<0.001) and higher median mRS (p<0.001) compared with those who did not at final follow-up. Despite this, almost two-thirds (64.1%) of patients undergoing a DC had a favourable outcome at this time-point. When compared with a propensity-matched cohort who did not, patients treated with DC fared worse at all endpoints. Multivariable logistic regression revealed that the presence of intracerebral haemorrhage (ICH) and increased pre-operative mid-line shift were predictive of undergoing DC, and WFNS grade ? 4 and a delayed ischaemic neurological deficit requiring endovascular angioplasty were associated with unfavourable outcome. Conclusions: Our data suggest that DC can be performed with acceptable rates of morbidity and mortality, particularly among younger patients who present with lower grade aSAH. Further research is required to determine the superiority, or otherwise, of DC compared with structured medical management of intracranial hypertension in this context, and to identify predictors of requiring decompressive surgery and patient outcome.

Purpose: To investigate the effect of scanner and prostate MRI acquisition characteristics when compared to PI-RADSv2.1 technical standards in the performance of a deep learning prostate segmentation model trained with data from one center (INST1), longitudinally evaluated at the same institution and when transferred to other institutions. Materials and Methods: In this retrospective study, a nn-UNet for prostate MRI segmentation was trained with data from 204 patients from one institution (INST1) (0.50mm2 in-plane, 3.6mm thickness and 16cm field of view [FOV]). Post-deployment performance at INST1 was tested with 30 patients acquired with a different protocol and in a different period of time (0.60mm2 in-plane, 4.0mm thickness and 19cm FOV). Transferability was tested on 248 patient sequences from five institutions (INST2, INST3, INST4, INST5 and INST6) acquired with different scanners and with heterogeneous degrees of PI-RADS v2.1 technical adherence. Performance was assessed using Dice Score Coefficient, Hausdorff Distance, Absolute Boundary Distance and Relative Volume Difference. Results: The model presented a significant degradation for the whole gland (WG) in the presence of a change of acquisition protocol at INST1 (DSC:99.46+0.12% and 91.24+3.32%,P<.001; RVD:-0.006+0.127% and 8.10+8.16%, P<.001). The model had a significantly higher performance in centers adhering to PI-RADS v2.1 when compared to those that did not (DSC: 86.24+9.67% and 74.83+15.45%, P <.001; RVD: -6.50+18.46% and 1.64+29.12%, P=.003). Conclusions: Adherence to PI-RADSv2.1 technical standards benefits inter-institutional transferability of a deep learning prostate segmentation model. Post-deployment evaluations are critical to ensure model performance is maintained over time in the presence of protocol acquisition modifications.

Objective: Postpartum women can develop post-traumatic stress disorder (PTSD) in response to complicated, traumatic childbirth; prevalence of these events remains high in the U.S. Currently, there is no recommended treatment approach in routine peripartum care for preventing maternal childbirth-related PTSD (CB-PTSD) and lessening its severity. Here, we provide a systematic review of available clinical trials testing interventions for the prevention and indication of CB-PTSD. Data Sources: We conducted a systematic review of PsycInfo, PsycArticles, PubMed (MEDLINE), ClinicalTrials.gov, CINAHL, ProQuest, Sociological Abstracts, Google Scholar, Embase, Web of Science, ScienceDirect, and Scopus through December 2022 to identify clinical trials involving CB-PTSD prevention and treatment. Study Eligibility Criteria: Trials were included if they were interventional, evaluated CB-PTSD preventive strategies or treatments, and reported outcomes assessing CB-PTSD symptoms. Duplicate studies, case reports, protocols, active clinical trials, and studies of CB-PTSD following stillbirth were excluded. Study Appraisal and Synthesis Methods: Two independent coders evaluated trials using a modified Downs and Black methodological quality assessment checklist. Sample characteristics and related intervention information were extracted via an Excel-based form. Results: A total of 33 studies, including 25 randomized controlled trials (RCTs) and 8 non-RCTs, were included. Trial quality ranged from Poor to Excellent. Trials tested psychological therapies most often delivered as secondary prevention against CB-PTSD onset (n=21); some examined primary (n=3) and tertiary (n=9) therapies. Positive treatment effects were found for early interventions employing conventional trauma-focused therapies, psychological counseling, and mother-infant dyadic focused strategies. Therapies' utility to aid women with severe acute traumatic stress symptoms or reduce incidence of CB-PTSD diagnosis is unclear, as is whether they are effective as tertiary intervention. Educational birth plan-focused interventions during pregnancy may improve maternal health outcomes, but studies remain scarce. Conclusions: An array of early psychological therapies delivered in response to traumatic childbirth, rather than universally, in the first postpartum days and weeks, may potentially buffer CB-PTSD development. Rather than one treatment being suitable for all, effective therapy should consider individual-specific factors. As additional RCTs generate critical information and guide recommendations for first-line preventive treatments for CB-PTSD, the psychiatric consequences associated with traumatic childbirth could be lessened.

Abstract Introduction Although the effectiveness of the HPV vaccine has been comprehensively described, adherence to dosing and limited budget is one of the causes of delay in HPV vaccination implementation in a country. A one-dose HPV vaccine could possibly solve those issues since several studies show promising results. Areas covered This is a systematic review and meta-analysis focusing on the effectiveness of the one-dose HPV vaccine compared to two- and three doses of vaccination. We focused on clinical effectiveness, including prevention of HPV16, HPV18, and hrHPV infection, HSIL or ASC-H incidence, and CIN II/III incidence. Expert opinion Our review showed that a one-dose HPV vaccine could potentially be as effective as two- or three doses since it offers immunogenic protection up to 8 years follow up and also prevention on infection and pre-cancers incidence. However, more studies and an extended duration of existing studies are required in order to provide robust evidence of this recommendation.

Background Exercise-based treatments can be harmful in people who were SARS-CoV-2 positive and living with post-COVID-19 condition (PL-PCC) and who have post-exertional malaise (PEM) or orthostatic intolerance (OI). Nevertheless, PEM and OI are not routinely assessed by clinicians. We estimated PEM and OI proportions in PL-PCC, as well in people not living with PCC (PnL-PCC) and negatives (i.e., never reported a SARS-CoV-2 positive test), and identified associated factors. Methods Participants from the PRIME post-COVID study were included. PEM and OI were assessed using validated questionnaires. PCC was defined as feeling unrecovered after SARS-CoV-2 infection. Multivariable regression analyses to study PEM and OI were stratified for sex. Results Data from 3,783 participants was analyzed. In PL-PCC, proportion of PEM was 48.1% and 41.2%, and proportion of OI was 29.3% and 27.9% in women and in men, respectively. Proportions were higher in PL-PCC compared to negatives, for PEM in women OR=4.38 [95%CI:3.01-6.38]; in men OR=4.78 [95%CI:3.13-7.29]; for OI in women 3.06 [95%CI:1.97-4.76]; in men 2.71 [95%CI:1.75-4.21]. Associated factors were age [≤]60 years, [≥]1 comorbidities and living alone. Conclusions High proportions of PEM and OI are observed in PL-PCC. Standard screening for PEM and OI is recommended in PL-PCC, to promote appropriate therapies. Trial registration ClinicalTrials.gov identifier:NCT05128695

Background: In 2021, the Health Resources and Services Administration (HRSA) launched the National Hypertension Control Initiative (HTN Initiative) with the goal to enhance HTN control through Bluetooth-enabled self-measured blood pressure (BT SMBP) monitoring and use this data to inform clinical decisions in Federally Qualified Health Centers (FQHCs) with large proportion of their population with uncontrolled BP. We sought to understand the experience of Michigan-based FQHCs in implementing the HTN initiative. Methods: Staff from three Michigan-based FQHCs were invited to participate in semi-structured interviews from September to November 2022. Interviews were conducted in-person and were based on the Tailored Implementation of Chronic Diseases framework. Content analysis was performed by three coders. Results: Ten staff participated in interviews (FQHC 1: n=6, FQHC 2: n=1, FQHC 3: n=3). The FQHCs differed in their stage of implementation and their approach. FQHC 1 created a large-scale, community health worker driven program, FQHC 2 created a small-scale, short term, BP device loan program, and FQHC 3 created a primarily outsourced, large-scale program through a contracted partner. Positive staff attitudes and outcome expectations, previous experience with SMBP grants, and supportive clinic leadership were identified as facilitators to implementation; Patients high social needs, SMBP-related Technology, and insufficient workforce and staff capacity were identified as barriers. Conclusion: BT SMBP among FQHC patients is promising but challenges in integrating SMBP data into clinic workflow, workforce capacity to support the high social needs of participants and to assist in reacting to the more frequent BP data remain to be overcome.

Background: The gold standard for outcome adjudication in clinical trials is chart review by a physician clinical events committee (CEC), which requires substantial time and expertise. Automated adjudication by natural language processing (NLP) may offer a more resource-efficient alternative. We previously showed that the Community Care Cohort Project (C3PO) NLP model adjudicates heart failure (HF) hospitalizations accurately within one healthcare system. Methods: This study externally validated the C3PO NLP model against CEC adjudication in the INVESTED trial. INVESTED compared influenza vaccination formulations in 5260 patients with cardiovascular disease at 157 North American sites. A central CEC adjudicated the cause of hospitalizations from medical records. We applied the C3PO NLP model to medical records from 4060 INVESTED hospitalizations and evaluated agreement between the NLP and final consensus CEC HF adjudications. We then fine-tuned the C3PO NLP model (C3PO+INVESTED) and trained a de novo model using half the INVESTED hospitalizations, and evaluated these models in the other half. NLP performance was benchmarked to CEC reviewer inter-rater reproducibility. Results: 1074 hospitalizations (26%) were adjudicated as HF by the CEC. There was high agreement between the C3PO NLP and CEC HF adjudications (agreement 87%, kappa statistic 0.69). C3PO NLP model sensitivity was 94% and specificity was 84%. The fine-tuned C3PO and de novo NLP models demonstrated agreement of 93% and kappa of 0.82 and 0.83, respectively. CEC reviewer inter-rater reproducibility was 94% (kappa 0.85). Conclusion: Our NLP model developed within a single healthcare system accurately identified HF events relative to the gold-standard CEC in an external multi-center clinical trial. Fine-tuning the model improved agreement and approximated human reproducibility. NLP may improve the efficiency of future multi-center clinical trials by accurately identifying clinical events at scale.

BACKGROUND: The incidence of stroke has increased for those < 64 years of age over the last decade. Control of hypertension is one of the greatest modifiable risk factors for preventing stroke but remains elusive. In 2017, the American College of Cardiology and American Heart Association national blood pressure guidelines tightened the definition of a normal blood pressure to <120/80 mm Hg, which if achieved would reduce stroke incidence by up to 21%. METHODS: This IRB approved cross-sectional study utilized stratified random sampling to recruit adults, 35 to 64 years of age with an active diagnosis of hypertension, no prior history of stroke or transient ischemic attack (TIA) and under current primary care. Blood pressure was dichotomized into controlled blood pressure (<120/80 mm Hg) and uncontrolled blood pressure (>120/80 mm Hg). Guided by a modified Health Belief Model, electronic surveys assessing individual medication compliance and beliefs about future stroke risk were distributed. Bivariate and multivariate logistic regression models analyzed the data with set at 0.05. RESULTS: Of the 304 subjects, 83% (n=253) had uncontrolled blood pressure, 78% of women and 89% of men, (77% of total subjects) classified as stage 1 or stage 2 hypertension. Men and women had mean composite compliancy scores below the 50th percentile (21.53 +/- 2.89). Women with uncontrolled hypertension were statistically less likely to be compliant (p= 0.040), with lower perceived susceptibility (p= 0.04) and severity of stroke (p=0.037) and less likely to see barriers to initiating exercise (p=0.04) but did not view exercise as beneficial in preventing stroke (p=0.039). CONCLUSION: Uncontrolled blood pressure remains problematic for both men and women. Women are known to have greater longevity and this study has identified targeted beliefs and behaviors that may more effectively address uncontrolled blood pressure in women at risk for future stroke.

Background: Levetiracetam is widely used in post stroke epilepsy. However, it is suspected to possess P-glycoprotein induction properties and therefore a potential significant interaction with DOACs . Our aim was to search for ischemic stroke signals with levetiracetam and the DOACs. Methods: In this retrospective, pharmacovigilance study, we used the Food and Drug Administration adverse event reporting system to identify ischemic stroke events associated with DOACs and concomitant use of levetiracetam. We evaluated disproportionate reporting by the reporting odds ratio adjusted to age and sex (adj.ROR) and the lower bound of the shrinkage 95% confidence interval ({Omega}025 > 0 is deemed significant for an interaction). Results: We identified 1,841 (1.5%), 3,731 (5.3%), 338 (4.9%), and 1,723 (1.3%), ischemic stroke reports with apixaban, dabigatran, edoxaban, and rivaroxaban respectively. When heparin/enoxaparin was used as the comparator the adjusted ROR of the interaction effect was 3.57 (95%CI, 2.81-4.58) between DOACs and levetiracetam. The shrinkage analysis detected an interaction between each of the DOACs and levetiracetam resulting in higher reports of ischemic stroke with the combination compared to each drug alone. The logistic model and shrinkage analysis failed to detect an interaction when queried for hemorrhagic stroke. Conclusions: We show a strong signal for the levetiracetam interaction with apixaban, dabigatran, edoxaban, and rivaroxaban leading to a 3-5 folds increased reporting risk of ischemic stroke. Our findings suggest the need for pharmacodynamic monitoring, while concomitantly prescribing levetiracetam with the DOACs.

Background Tuberculosis (TB) is a major public health concern, particularly among people living with the Human immunodeficiency Virus (PLWH). Accurate prediction of TB disease in this population is crucial for early diagnosis and effective treatment. Logistic regression and regularized machine learning methods have been used to predict TB, but their comparative performance in HIV patients remains unclear. The study aims to compare the predictive performance of logistic regression with that of regularized machine learning methods for TB disease in HIV patients. Methods Retrospective analysis of data from HIV patients diagnosed with TB in three hospitals in Kisumu County (JOOTRH, Kisumu sub-county hospital, Lumumba health center) between [dates]. Logistic regression, Lasso, Ridge, Elastic net regression were used to develop predictive models for TB disease. Model performance was evaluated using accuracy, and area under the receiver operating characteristic curve (AUC-ROC). Results Of the 927 PLWH included in the study, 107 (12.6%) were diagnosed with TB. Being in WHO disease stage III/IV (aOR: 7.13; 95%CI: 3.86-13.33) and having a cough in the last 4 weeks (aOR: 2.34;95%CI: 1.43-3.89) were significant associated with the TB. Logistic regression achieved accuracy of 0.868, and AUC-ROC of 0.744. Elastic net regression also showed good predictive performance with accuracy, and AUC-ROC values of 0.874 and 0.762, respectively. Conclusions Our results suggest that logistic regression, Lasso, Ridge regression, and Elastic net can all be effective methods for predicting TB disease in HIV patients. These findings may have important implications for the development of accurate and reliable models for TB prediction in HIV patients.

It has been presumed that rheumatoid arthritis (RA) joint pain is related to inflammation in the synovium; however, recent studies reveal that pain scores in patients do not correlate with synovial inflammation. We identified a module of 815 genes associated with pain, using a novel machine learning approach, Graph-based Gene expression Module Identification (GbGMI), in samples from patients with longstanding RA, but limited synovial inflammation at arthroplasty, and validated this finding in an independent cohort of synovial biopsy samples from early, untreated RA patients. Single-cell RNA-seq analyses indicated these genes were most robustly expressed by lining layer fibroblasts and receptor-ligand interaction analysis predicted robust lining layer fibroblast crosstalk with pain sensitive CGRP+ dorsal root ganglion sensory neurons. Netrin-4, which is abundantly expressed by lining fibroblasts and associated with pain, significantly increased the branching of pain-sensitive CGRP+ neurons in vitro. We conclude GbGMI is a useful method for identifying a module of genes that associate with a clinical feature of interest. Using this approach, we find that Netrin-4 is produced by synovial fibroblasts in the absence of inflammation and can enhance the outgrowth of CGRP+ pain sensitive nerve fibers.

During Covid-19, the Defense Health Agency's TRICARE insurance plan expanded its coverage to include 30.1% additional civilian healthcare providers. The DHA's Annual Report, however, states that TRICARE's provider directories are only 80% accurate. Although the DHA's 9.6 million beneficiaries need expanded access to care, they also require protection from misleading information, medical fraud, patient abuse, and identity theft. Since 2013, the Department of Health and Human Services' Office of the Inspector General has excluded 17,706 physicians from federal health programs due to misconduct. Patients who receive care from excluded providers experience worse medical outcomes. To determine if any excluded provider names were found on TRICARE's website, we performed background checks on TRICARE West's healthcare provider directory between January 1 and March 2023. Out of 39,463 provider names sampled from 22 states, there were 2,398 matches (6.08%) with individuals and businesses found in the OIG List of Excluded Individuals and Entities (OIG-LEIE), the GSA-SAM, the HHS HIPAA Breach Report, the International Trade Administration's Consolidated Screening List, the OIG-HHS Fugitive List, the FBI's January 6th Capitol Violence List of Charged Defendants, State Medicaid Exclusion Lists, and FDA Debarment Lists. Our study includes demographic analysis of the matching names and recommendations for an Insider Threat Management model. We recommend that DHA officials publish the National Provider Identification (NPI) numbers of all TRICARE providers. NPI numbers facilitate more accurate background checks of healthcare providers.