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1.
J Subst Use Addict Treat ; 167: 209505, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39241929

RESUMO

INTRODUCTION: Despite effective medications for opioid use disorder (MOUD), treatment engagement remains low. As the overdose crisis is increasingly characterized by opioids co-used with other substances, it is important to understand whether existing models effectively support treatment for patients who use multiple substances. Hospital-based addiction consultation services (ACS) have shown promise at increasing MOUD initiation and treatment engagement, but the effectiveness for patients with specific co-use patterns remains unknown. METHODS: Using 2016-2023 admissions data from a large safety net hospital, we estimated a random-effects logistic regression model to determine whether specific co-use (methamphetamine, cocaine, alcohol, sedative, and other) moderated the effect of being seen by ACS on the receipt of MOUD. Adjusting for patient sociodemographic, health, and admission characteristics we estimated the proportion of patients who received MOUD across specific co-use groups. RESULTS: Of 7679 total admissions indicating opioid use, of which 5266 (68.6 %) indicated co-use of one or more substances and 2387 (31.1 %) were seen by the ACS. Among admissions not seen by the ACS, a smaller proportion of admissions with any co-use received MOUD (23.5 %; 95 % CI: 21.9-25.1) compared to admissions with opioid use alone (34.0 %; 95 % CI: 31.9-36.1). However, among admissions seen by the ACS a similar proportion of admissions with any co-use received MOUD (57.8 %; 95 % CI: 55.5-60.1) as admissions with opioid use alone (56.2 %; 95 % CI: 52.2-60.2). The increase in proportion of admissions receiving MOUD associated with being seen by the ACS was larger for admissions with methamphetamine (38.6 percentage points; 95 % CI: 34.6-42.6) or cannabis co-use (39.0 percentage points; 95 % CI: 32.9-45.1) compared to admissions without methamphetamine (25.7 percentage points; 95 % CI: 22.2-29.2) or cannabis co-use (29.1 percentage points; 95 % CI: 26.1-32.1). CONCLUSIONS: The ACS is an effective hospital-based treatment model for increasing the proportion of admissions which receive MOUD. This study shows that ACSs are also able to support increased receipt of MOUD for patients who use other substances in addition to opioids. Future research is needed to further understand what transition strategies best support treatment linkage for patients who use multiple substances.

2.
Health Serv Res ; 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39256893

RESUMO

OBJECTIVE: To develop a method of consistently identifying interfacility transfers (IFTs) in Medicare Claims using patients with ST-Elevation Myocardial Infarction (STEMI) as an example. DATA SOURCES/STUDY SETTING: 100% Medicare inpatient and outpatient Standard Analytic Files and 5% Carrier Files, 2011-2020. STUDY DESIGN: Observational, cross-sectional comparison of patient characteristics between proposed and existing methods. DATA COLLECTION/EXTRACTION METHODS: We limited to patients aged 65+ with STEMI diagnosis using both proposed and existing methods. PRINCIPAL FINDINGS: We identified 62,668 more IFTs using the proposed method (86,128 versus 23,460). A separately billable interfacility ambulance trip was found for more IFTs using the proposed than existing method (86% vs. 79%). Compared with the existing method, transferred patients under the proposed method were more likely to live in rural (p < 0.001) and lower income (p < 0.001) counties and were located farther away from emergency departments, trauma centers, and intensive care units (p < 0.001). CONCLUSIONS: Identifying transferred patients based on two consecutive inpatient claims results in an undercount of IFTs and under-represents rural and low-income patients.

3.
Psychiatr Serv ; : appips20230639, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39257315

RESUMO

OBJECTIVE: The authors explored whether neighborhood context is associated with psychotropic polypharmacy and psychotherapy among a cohort of children with high needs for psychiatric and general medical care. METHODS: Electronic health record data from a large health care system were used in a cross-sectional design to examine psychotropic polypharmacy and psychotherapy in 2015-2019 among children ages 2-17 years (N=4,017) with geocoded addresses. Inclusion criteria were a diagnosis of a mental health condition, an intellectual and developmental disability, or a complex medical condition and one or more clinical encounters annually over the study period. Polypharmacy was defined as two or more psychotropic drug class prescriptions concurrently for ≥60 days. Psychotherapy was defined as receipt of any psychotherapy or adaptive behavior treatment. Neighborhood context (health, environment, education, and wealth) was measured with the Child Opportunity Index. Multilevel generalized linear mixed models with random intercept for census tracts were used to assess the associations between individual and neighborhood characteristics and psychotropic polypharmacy and psychotherapy. RESULTS: Moderate (vs. low) child opportunity was associated with higher odds of polypharmacy (adjusted OR [AOR]=1.79, 95% CI=1.19-2.67). High (vs. low) child opportunity was associated with higher odds of psychotherapy (AOR=2.15, 95% CI=1.43-3.21). Black (vs. White) race (AOR=0.51, 95% CI=0.37-0.71) and Hispanic ethnicity (AOR=0.44, 95% CI=0.26-0.73) were associated with lower odds of polypharmacy. CONCLUSIONS: Among high-need children, neighborhood Child Opportunity Index, race, and ethnicity were significantly associated with treatment outcomes in analyses adjusted for clinical factors. The findings underscore concerns about structural disparities and systemic racism and raise questions about access.

4.
bioRxiv ; 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39257795

RESUMO

Image-based profiling has been used to analyze cell health, drug mechanism of action, CRISPR-edited cells, and overall cytotoxicity. Cell Painting is a broadly used image-based assay that uses morphological features to capture how cells respond to treatments. However, this method requires cell fixation for staining, which prevents examining live cells. To address this limitation, here we present Live Cell Painting (LCP), a high-content method based on Acridine orange, a metachromatic dye that labels different organelles and cellular structures. We began by showing that LCP can be applied to follow acidic vesicle redistribution of cells exposed to acidic vesicles inhibitors. Next, we show that LCP can identify subtle changes in cells exposed to silver nanoparticles that are not detected by techniques such as MTT assay. In drug treatments, LCP was helpful in assessing the dose-response relationship and creating profiles that allow clustering of drugs that cause liver injury. Here, we present an affordable and easy-to-use image-based assay capable of assessing overall cell health and showing promise for use in various applications such as assessing drugs and nanoparticles. We envisage the use of Live Cell Painting as an initial screening of overall cell health while providing insights into new biological questions.

5.
J Subst Use Addict Treat ; 167: 209513, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39243980

RESUMO

INTRODUCTION: Due to the increasing role of psychostimulants in the US drug poisoning crisis, there is an increasing need to effectively implement evidence-based treatment for individuals with stimulant use disorder (StimUD). Contingency management is a behavioral strategy with robust evidence of support for the treatment of StimUD. In 2023, California initiated a large-scale effort to implement CM as a treatment for individuals with a stimulant use disorder (cocaine, methamphetamine, amphetamine) called the Recovery Incentives Program: California's Contingency Management Benefit. METHODS: The Recovery Incentives Program is being systematically implemented using the Becker et al. Science to Service Lab (SSL) implementation approach with several augmentations for this project. The SSL features three core components: didactic training, performance feedback, and external facilitation. We have augmented this approach with a readiness assessment process for sites prior to CM service launch, and an ongoing fidelity monitoring and feedback component post-launch. RESULTS: The present paper is a preliminary report describing the use of this augmented SSL strategy for CM implementation in a large-scale implementation effort. Data are presented to describe the implementation activities during the first ten months of the Recovery Incentives Program. CONCLUSION: The California Recovery Incentives Program has been systematically implemented and appears to be receiving a positive response from treatment program staff and enrolled members. Future papers and evaluation reports will continue to document member response to the Program and report on the ongoing training and implementation process.

6.
Asian Pac Isl Nurs J ; 8: e57187, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39250220

RESUMO

BACKGROUND: Doctor of Nursing Practice (DNP) programs in the United States confer the highest practice degree in nursing. The proportion of racial and ethnic minority DNP students, including those of Asian descent, keeps increasing in the United States. Statistics is commonly required for DNP programs. However, there is insufficient evidence regarding the number of years within which statistics should be taken and the minimum grade required for admission to the program. OBJECTIVE: This study aimed to examine the associations of statistics prerequisite durations and grades for admission with the course performances within the DNP program. We also explored whether a postadmission statistics overview course can prepare students for a DNP statistics course as well as a required statistics prerequisite course. METHODS: A retrospective cohort study was conducted with a sample of 31 DNP students at a large university in the Mid-Atlantic region. Statistical analysis of data collected over 5 years, between 2018 and 2022, was performed to examine the associations, using Spearman rank correlation analysis and Mann-Whitney U test (U). RESULTS: The performance of students in a DNP statistics course was not associated with prerequisite duration. There was no significant association between the duration and the DNP statistics course letter grades (ρ=0.12; P=.66), neither with exam 1 (ρ=0.03; P=.91) nor with exam 2 scores (ρ=0.01; P=.97). Prerequisite grades were positively associated with exam 1 grades (ρ=0.59; P=.02), but not exam 2 (ρ=0.35; P=.19) or course grades (ρ=0.40; P=.12). In addition, no difference was found in the performance of students whether meeting the prerequisite requirements or taking a 1-month, self-paced overview course (exam 1: U=159, P=.13; exam 2: U=102, P=.50; course letter grade: U=117, P=.92). CONCLUSIONS: No evidence was found to support the need for limits on when prerequisites are completed or grade requirements. Opting for a statistics overview course after admission can serve as a viable alternative to the statistics prerequisite, effectively preparing students for advanced quantitative data analysis in a DNP program.

8.
Sensors (Basel) ; 24(17)2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39275650

RESUMO

While interest in using wearable sensors to measure infant leg movement is increasing, attention should be paid to the characteristics of the sensors. Specifically, offset error in the measurement of gravitational acceleration (g) is common among commercially available sensors. In this brief report, we demonstrate how we measured the offset and other errors in three different off-the-shelf wearable sensors available to professionals and how they affected a threshold-based movement detection algorithm for the quantification of infant leg movement. We describe how to calibrate and correct for these offsets and how conducting this improves the reproducibility of results across sensors.


Assuntos
Algoritmos , Perna (Membro) , Movimento , Dispositivos Eletrônicos Vestíveis , Humanos , Movimento/fisiologia , Lactente , Perna (Membro)/fisiologia , Calibragem , Reprodutibilidade dos Testes , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Aceleração
10.
JAMA Netw Open ; 7(9): e2431512, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39226053

RESUMO

Importance: The emergence of acute neurological symptoms in children necessitates immediate intervention. Although low- and middle-income countries (LMICs) bear the highest burden of neurological diseases, there is a scarcity of diagnostic and therapeutic resources. Therefore, current understanding of the etiology of neurological emergencies in LMICs relies mainly on clinical diagnoses and verbal autopsies. Objective: To characterize the association of premortem neurological symptoms and their management with postmortem-confirmed cause of death among children aged younger than 5 years in LMICs and to identify current gaps and improve strategies to enhance child survival. Design, Setting, and Participants: This cross-sectional study was conducted between December 3, 2016, and July 22, 2022, at the 7 participating sites in the Child Health and Mortality Prevention Surveillance (CHAMPS) network (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa). Minimally invasive tissue sampling was performed at the CHAMPS sites with specimens from deceased children aged younger than 5 years. This study included deceased children who underwent a premortem neurological evaluation and had a postmortem-confirmed cause of death. Data analysis was performed between July 22, 2022, and January 15, 2023. Main Outcomes and Measures: Descriptive analysis was performed using neurological evaluations from premortem clinical records and from postmortem determination of cause of death (based on histopathology, microbiological testing, clinical records, and verbal autopsies). Results: Of the 2127 deaths of children codified during the study period, 1330 (62.5%) had neurological evaluations recorded and were included in this analysis. The 1330 children had a median age of 11 (IQR, 2-324) days; 745 (56.0%) were male and 727 (54.7%) presented with neurological symptoms during illness before death. The most common postmortem-confirmed neurological diagnoses related to death were hypoxic events (308 [23.2%]), meningoencephalitis (135 [10.2%]), and cerebral malaria (68 [5.1%]). There were 12 neonates with overlapping hypoxic events and meningoencephalitis, but there were no patients with overlapping meningoencephalitis and cerebral malaria. Neurological symptoms were similar among diagnoses, and no combination of symptoms was accurate in differentiating them without complementary tools. However, only 25 children (18.5%) with meningitis had a lumbar puncture performed before death. Nearly 90% of deaths (442 of 511 [86.5%]) with neurological diagnoses in the chain of events leading to death were considered preventable. Conclusions and Relevance: In this cross-sectional study of children aged younger than 5 years, neurological symptoms were frequent before death. However, clinical phenotypes were insufficient to differentiate the most common underlying neurological diagnoses. The low rate of lumbar punctures performed was especially worrying, suggesting a challenge in quality of care of children presenting with neurological symptoms. Improved diagnostic management of neurological emergencies is necessary to ultimately reduce mortality in this vulnerable population.


Assuntos
Causas de Morte , Países em Desenvolvimento , Humanos , Lactente , Pré-Escolar , Masculino , Estudos Transversais , Feminino , Países em Desenvolvimento/estatística & dados numéricos , Doenças do Sistema Nervoso/mortalidade , Quênia/epidemiologia , Recém-Nascido , África do Sul/epidemiologia , Bangladesh/epidemiologia , Etiópia/epidemiologia , Serra Leoa/epidemiologia , Mali/epidemiologia , Moçambique/epidemiologia , Autopsia/estatística & dados numéricos
11.
Cureus ; 16(8): e66796, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39268265

RESUMO

Fungal peritonitis is a somewhat rare yet serious complication associated with peritoneal dialysis (PD). It requires prompt diagnosis and treatment to prevent unnecessary morbidity and mortality. We present an unusual presentation that highlights the consequences of delayed diagnosis and management and propose methods for improving care for patients receiving peritoneal dialysis.

12.
JMIR Ment Health ; 11: e52363, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39136186

RESUMO

Background: The COVID-19 social distancing guidelines resulted in a dramatic transition to telephone and video technologies to deliver substance use disorder (SUD) treatment. Before COVID-19, the question was "Will telehealth ever take hold for SUD services?" Now that social distancing guidelines have been lifted, the question is "Will telehealth remain a commonly used care modality?" Objective: The principal purpose of this investigation was to examine the extent to which telehealth use in SUD service settings persisted following the lifting of COVID-19 safety distancing recommendations. Additionally, the study aimed to explore practitioners' perceptions of telehealth convenience and value after its regular implementation during the pandemic. Specifically, the goal of this study was to compare telehealth activity between time intervals: May-August 2020 (during peak COVID-19 safety distancing recommendations) and October-December 2022 (following discontinuation of distancing recommendations). Specifically, we compared (1) telehealth technologies and services, (2) perceived usefulness of telehealth, (3) ease of use of telephone- and video-based telehealth services, and (4) organizational readiness to use telehealth. Methods: An online cross-sectional survey consisting of 108 items was conducted to measure the use of telehealth technologies for delivering a specific set of SUD services in the United States and to explore the perceived readiness for use and satisfaction with telephonic and video services. The survey took approximately 25-35 minutes to complete and used the same 3 sets of questions and 2 theory-driven scales as in a previous cross-sectional survey conducted in 2020. Six of 10 Regional Addiction Technology Transfer Centers funded by the Substance Abuse and Mental Health Services Administration distributed the survey in their respective regions, collectively spanning 37 states. Responses of administrators and clinicians (hereafter referred to as staff) from this 2022 survey were compared to those obtained in the 2020 survey. Responses in 2020 and 2022 were anonymous and comprised two separate samples; therefore, an accurate longitudinal model could not be analyzed. Results: A total of 375 staff responded to the 2022 survey (vs 457 in 2020). Baseline organizational characteristics of the 2022 sample were similar to those of the 2020 sample. Phone and video telehealth utilization rates remained greater than 50% in 2022 for screening and assessment, case management, peer recovery support services, and regular outpatient services. The perceived usefulness of phone-based telehealth was higher in 2022 than in 2020 (mean difference [MD] -0.23; P=.002), but not for video-based telehealth (MD -0.12; P=.13). Ease of use of video-based telehealth was perceived as higher in 2022 than in 2020 (MD-0.35; P<.001), but no difference was found for phone-based telehealth (MD -0.12; P=.11). From the staff's perspective, patients had greater readiness for using telehealth via phone than video, but the staff perceived their personal and organizational readiness for using telehealth as greater for video-based than for phone-based telehealth. Conclusions: Despite lower telephone and video use in 2022 for telehealth services than in 2020, both modalities continue to be perceived positively. Future research may further determine the relative cost and clinical effectiveness of video-based services and thereby help to address some sources of the noted challenges to implementation by SUD organizations.


Assuntos
COVID-19 , Transtornos Relacionados ao Uso de Substâncias , Telemedicina , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Estudos Transversais , Distanciamento Físico , Inquéritos e Questionários , Masculino , Adulto , Feminino
13.
Telemed J E Health ; 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39166322

RESUMO

Background: The objective was to examine patient-reported outcomes (PROs) associated with access to a virtual clinic model for diabetes care. Methods: Adults with diabetes (N = 234) received virtual care, including support for continuous glucose monitoring (CGM) over a 6-month study period. Care was led by a Certified Diabetes Care and Education Specialist and focused on optimizing self-management skills and response to glucose values observed on CGM. After 6 months of CGM use and access to diabetes education, participants could opt in to another 6 months of follow-up with access to the virtual care team. Participants completed PRO surveys and had health and glycemic measures collected at baseline, 3, 6, and 12 months. Results: Participants with type 1 diabetes (N = 160) were 44 ± 14 years and had mean baseline HbA1c of 61 mmol/mol (7.7%). Participants with type 2 diabetes (N = 74) were 52 ± 12 years and had mean baseline HbA1c of 66 mmol/mol (8.2%). Compared with baseline levels, at 6 months participants experienced less depression, diabetes distress, and hypoglycemic fears while also experiencing greater satisfaction with glucose monitoring, diabetes technology and specifically with CGM, and confidence for managing hypoglycemic (p < 0.05). For participants with type 1 diabetes, more time in the target range for glucose levels (70-180 mg/dL) was associated with less depression, diabetes distress, and hypoglycemic fears. Conclusions: PROs improved for adults with diabetes utilizing virtual diabetes care, including support for CGM use. Paired with the glycemic improvements observed in this virtual clinic study, there were robust benefits on the quality of life of adults with diabetes. ClinicalTrials.gov Identifier: NCT04765358.

14.
Mov Disord ; 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39189078

RESUMO

BACKGROUND: Previous studies have suggested that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may have a disease-modifying effect in the development of Parkinson's disease (PD), but population studies yielded inconsistent results. OBJECTIVE: The aim was to compare the risk of PD associated with GLP-1RAs compared to dipeptidyl peptidase 4 inhibitors (DPP4i) among older adults with type 2 diabetes (T2D). METHODS: Using U.S. Medicare administrative data from 2016 to 2020, we conducted a population-based cohort study comparing the new use of GLP-1RA with the new use of DPP4i among adults aged ≥66 years with T2D. The primary endpoint was a new diagnosis of PD. A stabilized inverse probability of treatment weighting (sIPTW)-adjusted Cox proportional hazards regression model was employed to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for PD between GLP-1RA and DPP4i users. RESULTS: This study included 89,074 Medicare beneficiaries who initiated either GLP-1RA (n = 30,091) or DPP4i (n = 58,983). The crude incidence rate of PD was lower among GLP-1RA users than DPP4i users (2.85 vs. 3.92 patients per 1000 person-years). An sIPTW-adjusted Cox model showed that GLP-1RA users were associated with a 23% lower risk of PD than DPP4i users (HR, 0.77; 95% CI, 0.63-0.95). Our findings were largely consistent across different subgroup analyses such as sex, race, and molecular structure of GLP-1RA. CONCLUSION: Among Medicare beneficiaries with T2D, the new use of GLP-1RAs was significantly associated with a decreased risk of PD compared to the new use of DPP4i. © 2024 International Parkinson and Movement Disorder Society.

15.
Mol Neurodegener ; 19(1): 61, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39152475

RESUMO

BACKGROUND: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease characterized by the accumulation of aggregated tau proteins in astrocytes, neurons, and oligodendrocytes. Previous genome-wide association studies for PSP were based on genotype array, therefore, were inadequate for the analysis of rare variants as well as larger mutations, such as small insertions/deletions (indels) and structural variants (SVs). METHOD: In this study, we performed whole genome sequencing (WGS) and conducted association analysis for single nucleotide variants (SNVs), indels, and SVs, in a cohort of 1,718 cases and 2,944 controls of European ancestry. Of the 1,718 PSP individuals, 1,441 were autopsy-confirmed and 277 were clinically diagnosed. RESULTS: Our analysis of common SNVs and indels confirmed known genetic loci at MAPT, MOBP, STX6, SLCO1A2, DUSP10, and SP1, and further uncovered novel signals in APOE, FCHO1/MAP1S, KIF13A, TRIM24, TNXB, and ELOVL1. Notably, in contrast to Alzheimer's disease (AD), we observed the APOE ε2 allele to be the risk allele in PSP. Analysis of rare SNVs and indels identified significant association in ZNF592 and further gene network analysis identified a module of neuronal genes dysregulated in PSP. Moreover, seven common SVs associated with PSP were observed in the H1/H2 haplotype region (17q21.31) and other loci, including IGH, PCMT1, CYP2A13, and SMCP. In the H1/H2 haplotype region, there is a burden of rare deletions and duplications (P = 6.73 × 10-3) in PSP. CONCLUSIONS: Through WGS, we significantly enhanced our understanding of the genetic basis of PSP, providing new targets for exploring disease mechanisms and therapeutic interventions.


Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Paralisia Supranuclear Progressiva , Sequenciamento Completo do Genoma , Humanos , Paralisia Supranuclear Progressiva/genética , Predisposição Genética para Doença/genética , Masculino , Feminino , Idoso , Polimorfismo de Nucleotídeo Único/genética , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais
16.
PLoS Pathog ; 20(8): e1012448, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39146384

RESUMO

The chemokine co-receptors CXCR4 and CCR5 mediate HIV entry and signal transduction necessary for viral infection. However, to date only the CCR5 antagonist maraviroc is approved for treating HIV-1 infection. Given that approximately 50% of late-stage HIV patients also develop CXCR4-tropic virus, clinical anti-HIV CXCR4 antagonists are needed. Here, we describe a novel allosteric CXCR4 antagonist TIQ-15 which inhibits CXCR4-tropic HIV-1 infection of primary and transformed CD4 T cells. TIQ-15 blocks HIV entry with an IC50 of 13 nM. TIQ-15 also inhibits SDF-1α/CXCR4-mediated cAMP production, cofilin activation, and chemotactic signaling. In addition, TIQ-15 induces CXCR4 receptor internalization without affecting the levels of the CD4 receptor, suggesting that TIQ-15 may act through a novel allosteric site on CXCR4 for blocking HIV entry. Furthermore, TIQ-15 did not inhibit VSV-G pseudotyped HIV-1 infection, demonstrating its specificity in blocking CXCR4-tropic virus entry, but not CXCR4-independent endocytosis or post-entry steps. When tested against a panel of clinical isolates, TIQ-15 showed potent inhibition against CXCR4-tropic and dual-tropic viruses, and moderate inhibition against CCR5-tropic isolates. This observation was followed by a co-dosing study with maraviroc, and TIQ-15 demonstrated synergistic activity. In summary, here we describe a novel HIV-1 entry inhibitor, TIQ-15, which potently inhibits CXCR4-tropic viruses while possessing low-level synergistic activities against CCR5-tropic viruses. TIQ-15 could potentially be co-dosed with the CCR5 inhibitor maraviroc to block viruses of mixed tropisms.


Assuntos
Infecções por HIV , HIV-1 , Receptores CXCR4 , Internalização do Vírus , Humanos , Receptores CXCR4/antagonistas & inibidores , Receptores CXCR4/metabolismo , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Internalização do Vírus/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Inibidores da Fusão de HIV/farmacologia , Maraviroc/farmacologia , Triazóis/farmacologia , Fármacos Anti-HIV/farmacologia , Células HEK293
17.
iScience ; 27(8): 110525, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39156641

RESUMO

Elevated pernio incidence was observed during the COVID-19 pandemic. This prospective study enrolled subjects with pandemic-associated pernio in Wisconsin and Switzerland. Because pernio is a cutaneous manifestation of the interferonopathies, and type I interferon (IFN-I) immunity is critical to COVID-19 recovery, we tested the hypothesis that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated IFN-I signaling might underlie some pernio cases. Tissue-level IFN-I activity and plasmacytoid dendritic cell infiltrates were demonstrated in 100% of the Wisconsin cases. Across both cohorts, sparse SARS-CoV-2 RNA was captured in 25% (6/22) of biopsies, all with high inflammation. Affected patients lacked adaptive immunity to SARS-CoV-2. A hamster model of intranasal SARS-CoV-2 infection was used as a proof-of-principle experiment: RNA was detected in lungs and toes with IFN-I activity at both the sites, while replicating virus was found only in the lung. These data support a viral trigger for some pernio cases, where sustained local IFN-I activity can be triggered in the absence of seroconversion.

18.
Gynecol Oncol ; 190: 160-166, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39197415

RESUMO

OBJECTIVE: In 2012, updated ASCCP management guidelines for abnormal cervical cytology recommended observation rather than immediate referral to colposcopy for low-grade abnormalities in women ages 21-24. We evaluated the impact of these guidelines on changes in colposcopy procedure rates among young women. METHODS: We analyzed administrative and claims data from the largest statewide family planning program between July 2011 and June 2015. Using a difference-in-differences approach, we estimated changes in colposcopy procedure rates among women ages 21-24 years before and after the 2012 ASCCP management guidelines, relative to a comparison group of women ages 25-44. RESULTS: Our analysis included 333,977 women from 216 primary care provider sites. After publication of the 2012 ASCCP management guidelines, colposcopy rates significantly declined from 6.70% (95% CI 6.21-7.19) to 3.94% (95% CI 3.60-4.29) among women ages 21-24 and from 4.35% (95% CI 4.03-4.67) to 3.53% (3.25-3.80) among women over 24 years. These declines correspond to a 1.93 percentage point reduction (95% CI 1.62-2.25; p < 0.001) in colposcopy rate among women 21-24 vs. over 24 years, or a two-fold relative reduction. Among women ages 21-24, colposcopy receipt was associated with speaking primarily English vs. non-English (OR 1.46, 95% CI 1.35-1.57), having a cervical cytology test within the past year vs. not (OR 1.55, 95% CI 1.44-1.66), and receiving care from a public vs. private provider (OR 1.31, 95% CI 1.06-1.62). CONCLUSIONS: Colposcopy procedure rates among young women significantly declined following publication of the 2012 management guidelines, which has implications for reducing potential harms of overtreatment.

20.
J Emerg Nurs ; 50(5): 591-600, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39174190

RESUMO

INTRODUCTION: Workplace violence is a pervasive, perpetual, and underreported problem in the emergency department. Nurses experience devastating physical and psychological consequences owing to workplace violence exposure. Understanding workplace violence is challenging due to nurse underreporting. Improvement in capturing workplace violence cases can help drive data-informed, sustainable solutions to workplace violence prevention. The purpose of this project was to better capture the full extent of workplace violence in the emergency department through enhanced nurse workplace violence reporting. METHODS: In collaboration with emergency nurses and management, the project team used a multi-interventional approach and designed a feasible electronic reporting instrument to capture workplace violence events in real time by reducing nurse reporting barriers. Participating nurses accessed the instrument by scanning a quick-response code with their mobile phones. This code was strategically located on wall flyers and individual name badge stickers. Data were collected using Qualtrics software and analyzed using SPSS Statistics, which summarized the descriptive statistics. RESULTS: Two months after implementation, the electronic reporting instrument recorded 94 quick response code scans and 59 workplace violence reports, resulting in a 1080% increase in ED workplace violence reporting compared with the 2 months prior to implementation. The 59 workplace violence reports comprised 78% registered nurses, 19% emergency medical technicians, and 3% other health care workers. Workplace violence events were most frequent from 12:01 pm to 6:00 pm in treatment rooms (37%), triage (29%), waiting room (19%), behavioral health section (15%), and hallway (12%). DISCUSSION: A multi-interventional approach, coupled with a feasible, readily available electronic reporting instrument, enhanced ED workplace violence reporting and facilitated a better capture of ED workplace violence. Although nurse underreporting is still likely occurring, an emergence of workplace violence data trends can provide data-driven solutions in workplace violence prevention. Continued efforts to reduce the barriers that inhibit reporting are needed to foster a safe and supportive culture surrounding workplace violence reporting.


Assuntos
Enfermagem em Emergência , Serviço Hospitalar de Emergência , Recursos Humanos de Enfermagem Hospitalar , Melhoria de Qualidade , Violência no Trabalho , Humanos , Violência no Trabalho/prevenção & controle , Violência no Trabalho/estatística & dados numéricos , Enfermagem em Emergência/métodos , Recursos Humanos de Enfermagem Hospitalar/psicologia , Recursos Humanos de Enfermagem Hospitalar/estatística & dados numéricos , Feminino , Masculino
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