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1.
J Vasc Interv Radiol ; 2024 May 31.
Article in English | MEDLINE | ID: mdl-38825179

ABSTRACT

Reproductive outcomes after uterine artery embolization (UAE) for the treatment of uterine fibroids are challenging to study, leaving several unanswered questions surrounding the future fertility of patients undergoing the procedure. Subject matter experts from Interventional Radiology, Diagnostic Radiology, Obstetrics & Gynecology, and Reproductive Medicine participated in a Society of Interventional Radiology Foundation Research Consensus Panel to discuss and prioritize critical research topics focusing on fertility and reproductive outcomes in patients undergoing UAE for symptomatic uterine fibroids. After presentations and discussion of research ideas, the panelists prioritized the following topics for further investigation: 1) a prospective study of factors that influence implantation and gene expression in patients undergoing UAE or myomectomy over 1 year, 2) refinement of a classification system for uterine fibroids that can allow for more focused study design, which may include burden of fibroid disease, and 3) conjoint analysis/discrete choice experiments to better characterize those patients for whom fertility preservation is a high priority.

2.
Open Forum Infect Dis ; 11(3): ofae056, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38464490

ABSTRACT

Background: HIV pre-exposure prophylaxis (PrEP) uptake in women remains low. We developed a laboratory result-driven protocol to link women with a positive bacterial sexually transmitted infection (STI) to HIV PrEP at an urban safety-net hospital. Methods: Electronic health records of women with positive chlamydia, gonorrhea, and/or syphilis tests were reviewed, and those eligible for PrEP were referred for direct or primary care provider-driven outreach. We assessed the proportion of women with STIs who received PrEP offers, acceptance, and prescriptions before (July 1, 2018-December 31, 2018) and after (January 1, 2019-June 30, 2020) implementation to evaluate changes in the delivery of key elements of the PrEP care cascade (ie, PrEP offers, acceptance, and prescribing) for women with STIs after protocol implementation. Results: The proportion of women who received PrEP offers increased from 7.6% to 17.6% (P < .001). After multivariable adjustment, only the postintervention period was associated with PrEP offers (odds ratio [OR], 2.49; 95% CI, 1.68-3.68). In subgroup analyses, PrEP offers increased significantly among non-Hispanic Black (OR, 2.75; 95% CI, 1.65-4.58) and Hispanic (OR, 5.34; 95% CI, 1.77-16.11) women but not among non-Hispanic White women (OR, 1.49; 95% CI, 0.54-4.05). Significant changes in PrEP acceptance and prescriptions were not observed in the sample overall. Conclusions: A laboratory result-driven protocol was associated with a significant increase in PrEP offers to Black and Hispanic women with STI. These results provide concrete suggestions for health systems seeking to increase PrEP access and equity among women.

3.
CVIR Endovasc ; 7(1): 15, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38289433

ABSTRACT

BACKGROUND: There is a lack of registry studies about transradial access (TRA) outcomes. This prospective registry evaluated the TRA and procedure outcomes of visceral embolizations performed via TRA with 30-day follow-up. MATERIAL & METHODS: Prospective, multicenter registry included uterine fibroids (UFE), prostate artery (PAE), liver tumors (LT), and other hypervascular tumors (OHT) embolization performed in six US hospitals. Between February 2020 and January 2022, 99 patients underwent one radial artery visceral intervention (RAVI); 70 had UFE (70.7%), 16 PAE (16.2%), 7 LT (7.1%), and 6 OHT (6.1%). The mean age was 50.1 (±11.1) years, and 74/99 (74.7%) were females. The primary safety endpoints included hand ischemia, stroke, and death. Procedural success was defined as completing the intended procedure via radial artery (RA) access. Technical success was defined as the successful delivery of HydroPearl™ microspheres and complete embolization of the target vessel. RESULTS: Procedural and technical successes were 100% and 97%, respectively. There was no stroke, hand ischemia, radial-to-femoral conversion, access-related serious adverse events, or clinically evident radial artery occlusion at 30 days. There were two deaths: one respiratory failure and one progression of liver disease. Minor RA-related adverse event included arterial spasm, hematoma, and post-procedure discomfort. CONCLUSION: This prospective, multicenter, open-label registry confirmed the high safety profile and effectiveness of radial access in UFE, PAE, LT, and OHT embolization procedures without stroke, hand ischemia, or access-related serious adverse events at 30-day follow-up.

4.
J Vasc Interv Radiol ; 34(11): 1861-1867, 2023 11.
Article in English | MEDLINE | ID: mdl-37573000

ABSTRACT

PURPOSE: To evaluate if the addition of cone-beam computed tomography (CT) to digital subtraction angiography (DSA) improves the identification of the genicular arteries during genicular artery embolization (GAE) for knee pain secondary to osteoarthritis (OA). MATERIALS AND METHODS: This single-center study retrospectively analyzed 222 patients who underwent GAE for painful knee OA between May 2018 and April 2022. Intraprocedural cone-beam CT and DSA images were reviewed independently by 2 sets of interventional radiologists. DSA was performed for all patients. Technically adequate cone-beam CT was available for 205 patients (92.3%). The presence of the genicular arteries identified by cone-beam CT and DSA was compared using Φ coefficients. Embolization targets identified by both cone-beam CT and DSA were evaluated against those identified by DSA alone. RESULTS: Genicular arteries with the highest concordance between cone-beam CT and DSA were the inferior lateral (196 vs 198; Φ = 0.3530; P < .0001), superior lateral (197 vs 200; Φ = 0.3060; P < .0001), and superior medial genicular (186 vs 161; Φ = 0.2836; P < .0001) arteries. Cone-beam CT demonstrated higher rates of detection of the inferior medial (195 vs 178; Φ = 0.04573; P = .5150) and median genicular arteries (200 vs 192; Φ = 0.04573; P = .5150). Meanwhile, genicular arteries less frequently identified by cone-beam CT were the descending genicular (197 vs 200; Φ = -0.03186; P = .6502), superior patellar (175 vs 184; Φ = 0.1332; P = .0569), and recurrent anterior tibial (156 vs 186; Φ = 0.01809; P = .7969) arteries. Cone-beam CT in combination with DSA identified 13.4% (372 vs 328) more targets compared to DSA alone. CONCLUSIONS: Based on the results of the current study, cone-beam CT serves as a valuable adjunct for visualizing the genicular arteries during GAE, and together with DSA, it identifies more potential embolization targets.


Subject(s)
Embolization, Therapeutic , Osteoarthritis, Knee , Humans , Retrospective Studies , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/therapy , Arteries/diagnostic imaging , Cone-Beam Computed Tomography/methods , Angiography, Digital Subtraction/methods
5.
Semin Intervent Radiol ; 40(4): 349-356, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37575347

ABSTRACT

Placenta accreta spectrum is increasing in prevalence and poses significant risks to obstetric patients. This article defines characteristics, diagnosis, management, and outcomes of placenta accreta spectrum, highlighting interventional radiology's role in its management as part of a multidisciplinary approach.

6.
Int J Mol Sci ; 24(6)2023 Mar 08.
Article in English | MEDLINE | ID: mdl-36982250

ABSTRACT

Inflammatory conditions, including allergic asthma and conditions in which chronic low-grade inflammation is a risk factor, such as stress-related psychiatric disorders, are prevalent and are a significant cause of disability worldwide. Novel approaches for the prevention and treatment of these disorders are needed. One approach is the use of immunoregulatory microorganisms, such as Mycobacterium vaccae NCTC 11659, which have anti-inflammatory, immunoregulatory, and stress-resilience properties. However, little is known about how M. vaccae NCTC 11659 affects specific immune cell targets, including monocytes, which can traffic to peripheral organs and the central nervous system and differentiate into monocyte-derived macrophages that, in turn, can drive inflammation and neuroinflammation. In this study, we investigated the effects of M. vaccae NCTC 11659 and subsequent lipopolysaccharide (LPS) challenge on gene expression in human monocyte-derived macrophages. THP-1 monocytes were differentiated into macrophages, exposed to M. vaccae NCTC 11659 (0, 10, 30, 100, 300 µg/mL), then, 24 h later, challenged with LPS (0, 0.5, 2.5, 250 ng/mL), and assessed for gene expression 24 h following challenge with LPS. Exposure to M. vaccae NCTC 11659 prior to challenge with higher concentrations of LPS (250 ng/mL) polarized human monocyte-derived macrophages with decreased IL12A, IL12B, and IL23A expression relative to IL10 and TGFB1 mRNA expression. These data identify human monocyte-derived macrophages as a direct target of M. vaccae NCTC 11659 and support the development of M. vaccae NCTC 11659 as a potential intervention to prevent stress-induced inflammation and neuroinflammation implicated in the etiology and pathophysiology of inflammatory conditions and stress-related psychiatric disorders.


Subject(s)
Lipopolysaccharides , Mycobacterium , Humans , Lipopolysaccharides/pharmacology , Neuroinflammatory Diseases , Inflammation , Macrophages
7.
AIDS Patient Care STDS ; 37(4): 199-204, 2023 04.
Article in English | MEDLINE | ID: mdl-36961407

ABSTRACT

HIV and other sexually transmitted infections (STIs) are on the rise nationally and internationally. The coronavirus 2019 (COVID-19) pandemic drove a shift toward telemedicine and prioritization of symptomatic treatment over asymptomatic screening. The impact in safety-net settings, which faced disproportionate baseline STI/HIV rates rooted in structural inequities, and where many patients lack telemedicine resources, is not yet known. This study describes the impact of COVID-19 on STI/HIV testing at an urban safety-net hospital. We used descriptive statistics to compare hospital-wide chlamydia, gonorrhea, syphilis, and HIV testing volume and positivity rates in the following periods: prepandemic (July 1, 2019-February 29, 2020), peak-pandemic (March 1, 2020-May 31, 2020), and postpeak (June 1, 2020-August 31, 2021). STI and HIV test volume dropped sharply in March 2020. STI testing during the peak-pandemic period was 42% of prepandemic baseline (mean 1145 vs. 2738 tests/month) and nadired in April 2020 (766 tests/month). Similarly, peak-pandemic HIV testing was 43% of prepandemic baseline (mean 711 vs. 1635 tests/month) and nadired in April 2020 with 438 tests/month, concentrated in emergency department and inpatient settings. STI and HIV testing rates did not return to baseline for a full year. STI and HIV test positivity rates were higher in the peak-pandemic period compared with the prepandemic baseline. Given the precipitous decline in STI and HIV testing during the pandemic, safety-net settings should develop low-barrier alternatives to traditional office-based testing to mitigate testing gaps, high positivity rates, and associated morbidity.


Subject(s)
COVID-19 , Chlamydia Infections , Gonorrhea , HIV Infections , Sexually Transmitted Diseases , Syphilis , Humans , HIV Infections/diagnosis , HIV Infections/epidemiology , HIV Infections/prevention & control , Safety-net Providers , COVID-19/diagnosis , COVID-19/epidemiology , Sexually Transmitted Diseases/diagnosis , Sexually Transmitted Diseases/epidemiology , Sexually Transmitted Diseases/prevention & control , Gonorrhea/diagnosis , Syphilis/diagnosis , HIV Testing , Chlamydia Infections/diagnosis , Chlamydia Infections/epidemiology , Mass Screening
9.
Cardiovasc Intervent Radiol ; 46(5): 628-634, 2023 May.
Article in English | MEDLINE | ID: mdl-36949185

ABSTRACT

PURPOSE: Genicular artery embolization (GAE) is a new treatment option for symptomatic knee osteoarthritis. Genicular arterial anatomy is complex with limited published reports. This study describes the genicular artery anatomy utilizing intraprocedural cone-beam computed tomography (CBCT) during GAE. MATERIALS AND METHODS: This retrospective single-center study was approved by the institutional review board. All patients who underwent GAE between May 2018 and April 2022 were reviewed. Patients with a technically adequate CBCT were included in the analysis. CBCTs were analyzed to determine the presence, course, and branching patterns of the genicular arteries. RESULTS: A total of 222 patients underwent GAE and 205 (92%) were included for analysis. The descending genicular artery was present in 197 (96%) CBCTs with two branches in 152 (77%). The superior medial genicular artery (SMGA) was present in 186 (91%), superior lateral genicular artery (SLGA) in 203 (99%), inferior medial genicular artery (IMGA) in 195 (95%), inferior lateral genicular artery (ILGA) in 196 (95%), and median genicular artery (MGA) in 200 (97%). Four unique branching patterns were identified: common origin of SLGA and MGA (115, 56%), unique origins (45, 22%), trifurcation of SLGA, SMGA, and MGA (32, 15.5%), and common origin of SMGA and MGA (12, 6%). The recurrent ascending tibial was identified in 156 (76%) CBCTs and superior patellar artery in 175 (85%) CBCTs. CONCLUSION: Genicular artery anatomy is complex with numerous common variants. CBCT is a powerful adjunct in GAE to rapidly identify target vessels for embolization and potentially decrease the risk of nontarget embolization.


Subject(s)
Knee , Lower Extremity , Humans , Retrospective Studies , Knee/blood supply , Popliteal Artery , Cone-Beam Computed Tomography
10.
Open Forum Infect Dis ; 10(1): ofad006, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36726550

ABSTRACT

Among individuals presenting for monkeypox vaccination, transition from an opt-out protocol for sexually transmitted infection (STI) and HIV risk assessment and testing to an opt-in protocol was associated with a substantial increase in missed opportunities for HIV pre-exposure prophylaxis and STI testing at an ambulatory sexual health clinic.

11.
J Vasc Interv Radiol ; 34(2): 225-233, 2023 02.
Article in English | MEDLINE | ID: mdl-36306987

ABSTRACT

PURPOSE: To determine whether fallopian tube embolization with n-butyl-2-cyanoacrylate (nBCA) administered via a microcatheter in a rabbit model was technically feasible and resulted in short-term tubal occlusion. MATERIALS AND METHODS: In 10 female New Zealand white rabbits, the 2 cervices were cannulated using a 5-F catheter and hydrophilic guide wire transvaginally. Salpingography confirmed tubal patency bilaterally. A 2.4-F microcatheter was advanced to the distal fallopian tube, and nBCA/ethiodized oil was administered as the microcatheter was withdrawn to fill the length of the tube. A metallic coil was deployed prior to nBCA administration in half of the fallopian tubes. Rabbits were evaluated for tubal occlusion with salpingography at 1 month, followed by euthanasia and histopathologic analysis. Inflammation and fibrosis were graded from 0 (normal) to 3 (severe). RESULTS: Fallopian tube embolization was technically successful in 17 (85%) of 20 fallopian tubes. Thirteen (76%) of 17 embolized fallopian tubes were occluded at 1 month on salpingography (nBCA only, 7/9; nBCA and coil, 6/8). On histopathologic analysis, direct or indirect evidence of occlusion was observed in 14 (82%) of 17 fallopian tubes. Mild or early fibrosis was observed in 65% of the tubes. The mean inflammation and fibrosis scores for the embolized tubes were 0.62 and 0.94, respectively. CONCLUSIONS: This pilot study demonstrated that embolization of rabbit fallopian tubes using nBCA administered via a microcatheter is technically feasible and results in occlusion of most fallopian tubes in the short term with minimal inflammation. Investigation of efficacy in preventing pregnancy over the long term is warranted.


Subject(s)
Enbucrilate , Fallopian Tubes , Pregnancy , Humans , Rabbits , Female , Animals , Fallopian Tubes/diagnostic imaging , Fallopian Tubes/pathology , Fallopian Tubes/surgery , Feasibility Studies , Pilot Projects , Catheterization/methods , Inflammation/pathology , Fibrosis
12.
Support Care Cancer ; 30(11): 8919-8925, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35895158

ABSTRACT

OBJECTIVES: Recent studies have examined social needs (social determinants of health) among cancer survivors, but studies have not specifically focused on patients with leukemia or lymphoma. We examined food insecurity and other social needs among hematologic cancer survivors, including individuals who had completed primary therapy for leukemia, lymphoma, or multiple myeloma. A particular focus of the study was on the relationship between social needs and health-related quality of life. METHODS: We conducted a postal survey of a multiethnic cohort of hematologic cancer survivors who reside in Augusta, GA, or the surrounding area and who had been treated at the Georgia Cancer Center. RESULTS: A total of 53 patients with a history of hematologic cancer (leukemia, lymphoma, or multiple myeloma) completed the survey (10.6% response rate). The mean age was 62.6 years. The participants were diverse according to annual household income and employment status. About two-thirds were white and almost one-third were African American. Five of 52 participants (9.6%) experienced food insecurity. Patients with food insecurity had poorer HRQOL compared with those who were food secure (63.3 vs. 87.33, p = 0.0308). A similar pattern was seen for those who had difficulty paying utility bills, those who had housing insecurity, and those who had to go without health care because of a lack of transportation. Overall, there was a statistically significant inverse association between HRQOL and number of social needs (p = 0.004). CONCLUSION: When caring for cancer survivors, social needs such as food insecurity and housing insecurity are important considerations for oncologists and primary care providers, especially when caring for patients with lower socioeconomic status and racial/ethnic minorities.


Subject(s)
Cancer Survivors , Hematologic Neoplasms , Leukemia , Multiple Myeloma , Humans , Middle Aged , Quality of Life , Food Supply , Survivors
13.
DNA Repair (Amst) ; 118: 103381, 2022 10.
Article in English | MEDLINE | ID: mdl-35908367

ABSTRACT

Murine FAM72A, mFAM72A, binds the nuclear form of uracil-DNA glycosylase, mUNG2, inhibits its activity and causes its degradation. In immunoprecipitation assays the human paralog, hFAM72A, binds hUNG2 and is a potential anti-cancer drug target because of its high expression in many cancers. Using purified mFAM72A, and mUNG2 proteins we show that mFAM72A binds mUNG2, and the N-terminal 25 amino acids of mUNG2 bind mFAM72A at a nanomolar dissociation constant. We also show that mFAM72A is present throughout the cells, and mUNG2 helps localize it to nuclei. Based on in silico models of mFAM72A-mUNG2 interactions, we constructed several mutants of mFAM72A and found that while they have reduced ability to deplete mUNG2, the mutations also destabilized the former protein. We confirmed that Withaferin A, a predicted lead molecule for the design of FAM72A inhibitors, binds mFAM72A with micromolar affinity but has little affinity to mUNG2. We identified two potential metal-binding sites in mFAM72A and show that one of the sites contains an Fe-S cluster. This redox-sensitive cluster is involved in the mFAM72A-mUNG2 interaction and modulates mFAM72A activity. Hydrogen peroxide treatment of cells increases mUNG2 depletion in a FAM72A-dependent fashion suggesting that mFAM72A activity is redox-sensitive.


Subject(s)
Iron-Sulfur Proteins , Mitochondrial Proteins/metabolism , Uracil-DNA Glycosidase , Animals , Cell Nucleus/metabolism , Humans , Iron/metabolism , Iron-Sulfur Proteins/genetics , Mice , Oxidation-Reduction , Sulfur/metabolism , Uracil-DNA Glycosidase/metabolism
14.
Infant Behav Dev ; 68: 101748, 2022 08.
Article in English | MEDLINE | ID: mdl-35908421

ABSTRACT

The present study examined the frequency of gesture use and the relationship between frequency of gesture use and developmental abilities in typically developing 9- to 15-month-old, prelinguistic Hispanic and non-Hispanic White children. Data was collected through parent questionnaires, the Mullen Scales of Early Learning (MSEL), and two, 15-min video samples for each participant (semi-structured and structured settings). All video samples were coded for the frequency of the following gestures: total frequency, behavior regulation, social interaction, and joint attention. Results showed that children from both ethnicities used fewer gestures in a semi-structured setting in comparison to a structured setting and non-Hispanic White children produced higher frequencies of behavior regulation gestures and joint attention gestures, but lower frequencies of social interaction gestures. When controlling for ethnicity, gender, and age total frequency of gesture and frequencies of behavior regulation and social interaction were predictive of various developmental abilities. Furthermore, participant gender, age, and ethnicity were significantly related to various developmental abilities explored. These relationships were dependent upon setting. An understanding of the use of gesture and the relationship between gesture use and developmental abilities in prelinguistic children from different ethnic backgrounds has implication for early identification of delays and differences and is important to consider when exploring the connection between gesture and language and whether there are gesture-language, gesture-motor, and/or gesture-cognition integrated systems.


Subject(s)
Ethnicity , Gestures , Language , Child , Child Language , Cognition , Humans , Infant , Parents
15.
J Am Board Fam Med ; 35(3): 548-558, 2022.
Article in English | MEDLINE | ID: mdl-35641047

ABSTRACT

OBJECTIVE: The objective of this study was to adapt the National Diabetes Prevention Program (N-DPP) into a pragmatic tool for primary care settings by using daily text messaging to deliver all N-DPP content, supplemented by Fitbit technology to provide behavioral strategies typically delivered by personnel in traditional programs. Test the mobile health (mHealth), technology-based N-DPP adaptation (DPPFit) in primary care patients with prediabetes using a remote intervention based on the traditional 16 core sessions of the DPP. METHODS: A pilot study with pre/post survey analysis of aggregate data were used to determine changes in weight, physical activity, sedentary behavior, and associated diabetes risk outcomes among study participants (n = 33). In this study, participants were issued Fitbit devices and provided the remote intervention over 16 weeks via automated text messaging technology, which followed the content of the DPP core education sessions. RESULTS: Data analysis from baseline to 6-month follow-up demonstrate mean weight loss of 3.3 kg (95% CI: -6.2 to -0.5; P = .026), reduction in body mass index by 1.25 points (95% CI: -2.1 to -0.4; P = .005), a significant average increase of 2 days in self-reported physical activity per week (95% CI: 0.4 to 3.6; P = .015) and an average 10% decrease in sedentary time (P = .007). CONCLUSIONS: The remote DPPFit intervention demonstrates a promising and practical approach to the management of prediabetes in a primary care setting. The results support the use of the DPPFit program and application to achieve meaningful outcomes in a population with prediabetes. A randomized controlled trial with a larger sample is warranted.


Subject(s)
Diabetes Mellitus, Type 2 , Prediabetic State , Diabetes Mellitus, Type 2/prevention & control , Humans , Pilot Projects , Prediabetic State/diagnosis , Prediabetic State/therapy , Primary Health Care , Technology
16.
Sci Rep ; 12(1): 2097, 2022 02 08.
Article in English | MEDLINE | ID: mdl-35136132

ABSTRACT

The disaccharide trehalose is essential for viability of Mycobacterium tuberculosis, which synthesizes trehalose de novo but can also utilize exogenous trehalose. The mycobacterial cell wall encompasses two permeability barriers, the cytoplasmic membrane and the outer mycolic acid-containing mycomembrane. The ABC transporter LpqY-SugA-SugB-SugC has previously been demonstrated to mediate the specific uptake of trehalose across the cytoplasmic membrane. However, it is still unclear how the transport of trehalose molecules across the mycomembrane is mediated. In this study, we harnessed the antimycobacterial activity of the analogue 6-azido trehalose to select for spontaneous resistant M. tuberculosis mutants in a merodiploid strain harbouring two LpqY-SugA-SugB-SugC copies. Mutations mediating resistance to 6-azido trehalose mapped to the proline-proline-glutamate (PPE) family member PPE51 (Rv3136), which has recently been shown to be an integral mycomembrane protein involved in uptake of low-molecular weight compounds. A site-specific ppe51 gene deletion mutant of M. tuberculosis was unable to grow on trehalose as the sole carbon source. Furthermore, bioorthogonal labelling of the M. tuberculosis Δppe51 mutant incubated with 6-azido trehalose corroborated the impaired internalization. Taken together, the results indicate that the transport of trehalose and trehalose analogues across the mycomembrane of M. tuberculosis is exclusively mediated by PPE51.


Subject(s)
ATP-Binding Cassette Transporters , Azides , Bacterial Outer Membrane , Bacterial Proteins , Mycobacterium tuberculosis , Trehalose , ATP-Binding Cassette Transporters/genetics , ATP-Binding Cassette Transporters/metabolism , Azides/chemistry , Azides/metabolism , Bacterial Outer Membrane/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Mutation , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/metabolism , Trehalose/analogs & derivatives , Trehalose/chemistry , Trehalose/metabolism
18.
J Int Assoc Provid AIDS Care ; 21: 23259582211073393, 2022.
Article in English | MEDLINE | ID: mdl-35001723

ABSTRACT

Identifying candidates for HIV pre-exposure prophylaxis (PrEP) is a barrier to improving PrEP uptake in priority populations. Syphilis infection is an indication for PrEP in all individuals and can be easily assessed by primary care providers (PCP) and health systems. This retrospective study evaluated the impact of a multidisciplinary provider outreach intervention on PrEP uptake in patients with a positive syphilis test result in a safety-net hospital-based primary care practice. The PCPs of PrEP-eligible patients with a positive syphilis result were notified via the electronic medical record (EMR) about potential PrEP eligibility and institutional HIV PrEP resources. Rates of PrEP offers and prescriptions were compared in the pre (8/1/2018-12/31/2018, n = 60) and post (1/1/2019-5/31/2019, n = 86) intervention periods. Secondary analyzes evaluated receipt of appropriate syphilis treatment and contemporaneous screening for HIV, gonorrhea, and chlamydia. No significant differences in the overall proportion of patients offered (15% vs 19%) and prescribed (7% vs 5%) PrEP were observed between the pre- and post-periods. Overall, 7% of positive tests represented infectious syphilis. The rate of appropriate syphilis treatment was equivalent (57% vs 56%) and contemporaneous screening for other sexually transmitted infections was suboptimal across the entire study period. Although any positive syphilis test may be an easily abstracted metric from the EMR, this approach was inclusive of many patients without current HIV risk and did not increase PrEP uptake significantly. Future research into population health approaches to increase HIV prevention should focus on patients with infectious syphilis and other current risk factors for incident HIV infection.


Subject(s)
HIV Infections , Pre-Exposure Prophylaxis , Syphilis , HIV Infections/prevention & control , Humans , Primary Health Care , Retrospective Studies , Syphilis/diagnosis , Syphilis/drug therapy , Syphilis/epidemiology
19.
Intell Based Med ; 6: 100049, 2022.
Article in English | MEDLINE | ID: mdl-35039806

ABSTRACT

BACKGROUND: Deep learning-based radiological image analysis could facilitate use of chest x-rays as a triaging tool for COVID-19 diagnosis in resource-limited settings. This study sought to determine whether a modified commercially available deep learning algorithm (M-qXR) could risk stratify patients with suspected COVID-19 infections. METHODS: A dual track clinical validation study was designed to assess the clinical accuracy of M-qXR. The algorithm evaluated all Chest-X-rays (CXRs) performed during the study period for abnormal findings and assigned a COVID-19 risk score. Four independent radiologists served as radiological ground truth. The M-qXR algorithm output was compared against radiological ground truth and summary statistics for prediction accuracy were calculated. In addition, patients who underwent both PCR testing and CXR for suspected COVID-19 infection were included in a co-occurrence matrix to assess the sensitivity and specificity of the M-qXR algorithm. RESULTS: 625 CXRs were included in the clinical validation study. 98% of total interpretations made by M-qXR agreed with ground truth (p = 0.25). M-qXR correctly identified the presence or absence of pulmonary opacities in 94% of CXR interpretations. M-qXR's sensitivity, specificity, PPV, and NPV for detecting pulmonary opacities were 94%, 95%, 99%, and 88% respectively. M-qXR correctly identified the presence or absence of pulmonary consolidation in 88% of CXR interpretations (p = 0.48). M-qXR's sensitivity, specificity, PPV, and NPV for detecting pulmonary consolidation were 91%, 84%, 89%, and 86% respectively. Furthermore, 113 PCR-confirmed COVID-19 cases were used to create a co-occurrence matrix between M-qXR's COVID-19 risk score and COVID-19 PCR test results. The PPV and NPV of a medium to high COVID-19 risk score assigned by M-qXR yielding a positive COVID-19 PCR test result was estimated to be 89.7% and 80.4% respectively. CONCLUSION: M-qXR was found to have comparable accuracy to radiological ground truth in detecting radiographic abnormalities on CXR suggestive of COVID-19.

20.
Nature ; 600(7888): 324-328, 2021 12.
Article in English | MEDLINE | ID: mdl-34819670

ABSTRACT

Activation-induced cytidine deaminase (AID) catalyses the deamination of deoxycytidines to deoxyuracils within immunoglobulin genes to induce somatic hypermutation and class-switch recombination1,2. AID-generated deoxyuracils are recognized and processed by subverted base-excision and mismatch repair pathways that ensure a mutagenic outcome in B cells3-6. However, why these DNA repair pathways do not accurately repair AID-induced lesions remains unknown. Here, using a genome-wide CRISPR screen, we show that FAM72A is a major determinant for the error-prone processing of deoxyuracils. Fam72a-deficient CH12F3-2 B cells and primary B cells from Fam72a-/- mice exhibit reduced class-switch recombination and somatic hypermutation frequencies at immunoglobulin and Bcl6 genes, and reduced genome-wide deoxyuracils. The somatic hypermutation spectrum in B cells from Fam72a-/- mice is opposite to that observed in mice deficient in uracil DNA glycosylase 2 (UNG2)7, which suggests that UNG2 is hyperactive in FAM72A-deficient cells. Indeed, FAM72A binds to UNG2, resulting in reduced levels of UNG2 protein in the G1 phase of the cell cycle, coinciding with peak AID activity. FAM72A therefore causes U·G mispairs to persist into S phase, leading to error-prone processing by mismatch repair. By disabling the DNA repair pathways that normally efficiently remove deoxyuracils from DNA, FAM72A enables AID to exert its full effects on antibody maturation. This work has implications in cancer, as the overexpression of FAM72A that is observed in many cancers8 could promote mutagenesis.


Subject(s)
B-Lymphocytes , DNA Glycosylases , DNA Mismatch Repair , Immunoglobulin Class Switching , Membrane Proteins , Mutation , Neoplasm Proteins , Somatic Hypermutation, Immunoglobulin , Animals , Female , Humans , Mice , B-Lymphocytes/metabolism , CRISPR-Cas Systems , DNA Glycosylases/antagonists & inhibitors , DNA Glycosylases/metabolism , Epistasis, Genetic , HEK293 Cells , Immunoglobulin Class Switching/genetics , Immunoglobulin Switch Region/genetics , Membrane Proteins/deficiency , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mice, Inbred C57BL , MutS Homolog 2 Protein/genetics , MutS Homolog 2 Protein/metabolism , Neoplasm Proteins/deficiency , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Somatic Hypermutation, Immunoglobulin/genetics
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