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1.
J Gen Intern Med ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987479

ABSTRACT

BACKGROUND: The opioid overdose epidemic disproportionately impacts people experiencing homelessness. Outpatient-based opioid treatment (OBOT) programs have been established in homeless health care settings across the USA, but little is known about the success of these programs in engaging and retaining this highly marginalized patient population in addiction care. OBJECTIVE: To evaluate predictors of initial engagement and subsequent attendance in a homeless-tailored OBOT program. DESIGN: Prospective cohort study with 4 months of follow-up. PARTICIPANTS: A total of 148 homeless-experienced adults (≥18 years) who newly enrolled in the Boston Healthcare for the Homeless Program (BHCHP) OBOT program over a 1-year period (1/6/2022-1/5/2023). MAIN MEASURES: The primary outcomes were (1) initial OBOT program engagement, defined as having ≥2 additional OBOT visits within 1 month of OBOT enrollment, and (2) subsequent OBOT program attendance, measured monthly from months 2 to 4 of follow-up. KEY RESULTS: The average age was 41.7 years (SD 10.2); 23.6% were female, 35.8% were Hispanic, 12.8% were non-Hispanic Black, and 43.9% were non-Hispanic White. Over one-half (57.4%) were initially engaged. OBOT program attendances during months 2, 3, and 4 were 60.8%, 50.0%, and 41.2%, respectively. One-quarter (24.3%) were initially engaged and then attended the OBOT program every month during the follow-up period. Participants in housing or residential treatment programs (vs. unhoused; adjusted odds ratios (aORs) = 2.52; 95% CI = 1.17-5.44) and those who were already on or initiated a medication for opioid use disorder (OUD) (aOR = 6.53; 95% CI = 1.62-26.25) at the time of OBOT enrollment had higher odds of engagement. Older age (aOR = 1.74 per 10-year increment; 95% CI = 1.28-2.38) and initial engagement (aOR = 3.50; 95% CI = 1.86-6.59) conferred higher odds of attendance. CONCLUSIONS: In this study, over half initially engaged with the OBOT program, with initial engagement emerging as a strong predictor of subsequent OBOT program attendance. Interventions aimed at enhancing initial OBOT program engagement, including those focused on housing and buprenorphine initiation, may improve longer-term outcomes in this marginalized population.

2.
Front Behav Neurosci ; 18: 1341705, 2024.
Article in English | MEDLINE | ID: mdl-38983870

ABSTRACT

The retrosplenial cortex (RSC) is well-known for its contribution to episodic memory, as well as contextual and spatial learning and memory. However, two literatures have also emerged examining the role of the RSC in aversive conditioning. The purpose of this manuscript is to review, and attempt to integrate, these two literatures. We focus on studies in which discrete cues, such as tones, predict the occurrence of aversive outcomes, such as mild shocks. Using both electrophysiological recordings and lesion methods, the first literature has examined RSC contributions to discriminative avoidance conditioning. The second, and more recent literature, has focused on the role of the RSC in Pavlovian fear conditioning. We discuss both literatures in terms of the type of information processed by the RSC, the role of the RSC in memory storage, and how the aversive conditioning literature might be consistent with a role for the RSC in contextual learning and memory.

3.
Sci Rep ; 14(1): 15821, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982149

ABSTRACT

Adenoid cystic carcinoma (AdCC) is a slow-growing salivary gland malignancy that relapses frequently. AdCCs of the submandibular gland exhibit unique differences in prognosis and treatment response to adjuvant radiotherapy compared to other sites, yet the role of tumor anatomic subsite on gene expression and tumor immune microenvironment (TIME) composition remains unclear. We used 87 samples, including 48 samples (27 AdCC and 21 normal salivary gland tissue samples) from 4 publicly available AdCC RNA sequencing datasets, a validation set of 33 minor gland AdCCs, and 39 samples from an in-house cohort (30 AdCC and 9 normal salivary gland samples). RNA sequencing data were used for single sample gene set enrichment analysis and TIME deconvolution. Quantitative PCR and multiplex immunofluorescence were performed on the in-house cohort. Wilcoxon rank-sum, nonparametric equality-of-medians tests and linear regression models were used to evaluate tumor subsite differences. AdCCs of different anatomic subsites including parotid, submandibular, sublingual, and minor salivary glands differed with respect to expression of several key tumorigenic pathways. Among the three major salivary glands, the reactive oxygen species (ROS)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway signature was significantly underexpressed in AdCC of submandibular compared to parotid and sublingual glands while this association was not observed among normal glands. Additionally, the NRF2 pathway, whose expression was associated with favorable overall survival, was overexpressed in AdCCs of parotid gland compared to minor and submandibular glands. The TIME deconvolution identified differences in CD4+ T cell populations between AdCC of major and minor glands and natural killer (NK) cells among AdCC of minor, submandibular, and parotid glands while plasma cells were enriched in normal submandibular glands compared to other normal gland controls. Our data reveal key molecular differences in AdCC of different anatomic subsites. The ROS and NRF2 pathways are underexpressed in submandibular and minor AdCCs compared to parotid gland AdCCs, and NRF2 pathway expression is associated with favorable overall survival. The CD4+ T, NK, and plasma cell populations also vary by tumor subsites, suggesting that the observed submandibular AdCC tumor-intrinsic pathway differences may be responsible for influencing the TIME composition and survival differences.


Subject(s)
Carcinoma, Adenoid Cystic , Salivary Gland Neoplasms , Tumor Microenvironment , Humans , Carcinoma, Adenoid Cystic/pathology , Carcinoma, Adenoid Cystic/immunology , Carcinoma, Adenoid Cystic/metabolism , Carcinoma, Adenoid Cystic/genetics , Salivary Gland Neoplasms/pathology , Salivary Gland Neoplasms/immunology , Salivary Gland Neoplasms/genetics , Salivary Gland Neoplasms/metabolism , Salivary Gland Neoplasms/mortality , Male , Female , Tumor Microenvironment/immunology , Middle Aged , Aged , Gene Expression Regulation, Neoplastic , Adult , Salivary Glands/pathology , Salivary Glands/metabolism , Salivary Glands/immunology , Prognosis
5.
Energy Environ Sci ; 17(12): 4137-4146, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38899028

ABSTRACT

Controlling solid electrolyte interphase (SEI) in batteries is crucial for their efficient cycling. Herein, we demonstrate an approach to enable robust battery performance that does not rely on high fractions of fluorinated species in electrolytes, thus substantially decreasing the environmental footprint and cost of high-energy batteries. In this approach, we use very low fractions of readily reducible fluorinated cations in electrolyte (∼0.1 wt%) and employ electrostatic attraction to generate a substantial population of these cations at the anode surface. As a result, we can form a robust fluorine-rich SEI that allows for dendrite-free deposition of dense Li and stable cycling of Li-metal full cells with high-voltage cathodes. Our approach represents a general strategy for delivering desired chemical species to battery anodes through electrostatic attraction while using minute amounts of additive.

6.
JAMA Intern Med ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38856994

ABSTRACT

Importance: People experiencing homelessness die of lung cancer at rates more than double those in the general population. Lung cancer screening (LCS) with low-dose computed tomography (LDCT) reduces lung cancer mortality, but the circumstances of homelessness create barriers to LCS participation. Objective: To determine whether patient navigation, added to usual care, improved LCS LDCT receipt at a large Health Care for the Homeless (HCH) program. Design, Setting, and Participants: This parallel group, pragmatic, mixed-methods randomized clinical trial was conducted at Boston Health Care for the Homeless Program (BHCHP), a federally qualified HCH program that provides tailored, multidisciplinary care to nearly 10 000 homeless-experienced patients annually. Eligible individuals had a lifetime history of homelessness, had a BHCHP primary care practitioner (PCP), were proficient in English, and met the pre-2022 Medicare coverage criteria for LCS (aged 55-77 years, ≥30 pack-year history of smoking, and smoking within the past 15 years). The study was conducted between November 20, 2020, and March 29, 2023. Intervention: Participants were randomized 2:1 to usual BHCHP care either with or without patient navigation. Following a theory-based, patient-centered protocol, the navigator provided lung cancer education, facilitated LCS shared decision-making visits with PCPs, assisted participants in making and attending LCS LDCT appointments, arranged follow-up when needed, and offered tobacco cessation support for current smokers. Main Outcomes and Measures: The primary outcome was receipt of a 1-time LCS LDCT within 6 months after randomization, with between-group differences assessed by χ2 analysis. Qualitative interviews assessed the perceptions of participants and PCPs about the navigation intervention. Results: In all, 260 participants (mean [SD] age, 60.5 [4.7] years; 184 males [70.8%]; 96 non-Hispanic Black participants [36.9%] and 96 non-Hispanic White participants [36.9%]) were randomly assigned to usual care with (n = 173) or without (n = 87) patient navigation. At 6 months after randomization, 75 participants in the patient navigation arm (43.4%) and 8 of those in the usual care-only arm (9.2%) had completed LCS LDCT (P < .001), representing a 4.7-fold difference. Interviews with participants in the patient navigation arm and PCPs identified key elements of the intervention: multidimensional social support provision, care coordination activities, and interpersonal skills of the navigator. Conclusions and Relevance: In this randomized clinical trial, patient navigation support produced a 4.7-fold increase in 1-time LCS LDCT completion among HCH patients in Boston. Future work should focus on longer-term screening participation and outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT04308226.

7.
Behav Neurosci ; 2024 May 16.
Article in English | MEDLINE | ID: mdl-38753399

ABSTRACT

Pavlovian extinction reduces the performance of conditioned responses and occurs when the conditioned stimulus (CS) is repeatedly presented in the absence of the unconditioned stimulus (US). However, when the CS is experienced in a context that is different from the extinction context, there is a recovery of the conditioned response, a phenomenon known as renewal. There is some evidence that the renewal of appetitive conditioning is influenced by sex, with females failing to exhibit renewed responding. Further, there is recent evidence that renewal of fear might also not occur in female rats. In both appetitive and fear preparations, the lack of renewal in females has been postulated to be related to cycling ovarian hormones. Therefore, in Experiments 1 and 2, we directly compared fear renewal in males and females (Experiment 1) as well as ovariectomized (OVX) females (Experiment 2) when conditioning occurred in Context A, extinction in B, and testing in A (ABA renewal). Experiments 3 and 4 examined renewal when conditioning and extinction occurred in A and testing occurred in B (AAB renewal). In all experiments, renewal was not significantly different between male and female rats. Further, in Experiments 2 and 4, renewal did not differ between males, intact females, and OVX females. Additionally, in each experiment, there was no evidence that context excitation and/or inhibition contributed to renewal; instead suggesting that renewal was controlled by an occasion-setting mechanism. Overall, these results suggest little evidence for the role of sex in renewal of conditioned freezing and also indicate that cycling ovarian hormones have little role in the strength of renewal in female rats. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

8.
Viruses ; 16(4)2024 03 29.
Article in English | MEDLINE | ID: mdl-38675879

ABSTRACT

Human papillomavirus-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) is the most common HPV-associated cancer in the United States, with a rapid increase in incidence over the last two decades. The burden of HPV+ HNSCC is likely to continue to rise, and given the long latency between infection and the development of HPV+ HNSCC, it is estimated that the effect of the HPV vaccine will not be reflected in HNSCC prevalence until 2060. Efforts have begun to decrease morbidity of standard therapies for this disease, and its improved characterization is being leveraged to identify and target molecular vulnerabilities. Companion biomarkers for new therapies will identify responsive tumors. A more basic understanding of two mechanisms of HPV carcinogenesis in the head and neck has identified subtypes of HPV+ HNSCC that correlate with different carcinogenic programs and that identify tumors with good or poor prognosis. Current development of biomarkers that reliably identify these two subtypes, as well as biomarkers that can detect recurrent disease at an earlier time, will have immediate clinical application.


Subject(s)
Biomarkers, Tumor , Head and Neck Neoplasms , Papillomavirus Infections , Precision Medicine , Squamous Cell Carcinoma of Head and Neck , Humans , Papillomavirus Infections/virology , Papillomavirus Infections/diagnosis , Papillomavirus Infections/therapy , Head and Neck Neoplasms/therapy , Head and Neck Neoplasms/virology , Squamous Cell Carcinoma of Head and Neck/virology , Squamous Cell Carcinoma of Head and Neck/therapy , Precision Medicine/methods , Neoplasm Recurrence, Local/virology , Papillomaviridae/genetics , Papillomaviridae/classification
9.
Nat Chem ; 16(6): 922-929, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38570729

ABSTRACT

Lithium metal batteries represent a promising technology for next-generation energy storage, but they still suffer from poor cycle life due to lithium dendrite formation and cathode cracking. Fluorinated solvents can improve battery longevity by improving LiF content in the solid-electrolyte interphase; however, the high cost and environmental concerns of fluorinated solvents limit battery viability. Here we designed a series of fluorine-free solvents through the methylation of 1,2-dimethoxyethane, which promotes inorganic LiF-rich interphase formation through anion reduction and achieves high oxidation stability. The anion-derived LiF interphases suppress lithium dendrite growth on the lithium anode and minimize cathode cracking under high-voltage operation. The Li+-solvent structure is investigated through in situ techniques and simulations to draw correlations between the interphase compositions and electrochemical performances. The methylation strategy provides an alternative pathway for electrolyte engineering towards high-voltage electrolytes while reducing dependence on expensive fluorinated solvents.

10.
J Mol Diagn ; 26(7): 563-573, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38588769

ABSTRACT

Clonal hematopoiesis of indeterminate potential (CHIP) is a common age-related phenomenon in which hematopoietic stem cells acquire mutations in a select set of genes commonly mutated in myeloid neoplasia which then expand clonally. Current sequencing assays to detect CHIP mutations are not optimized for the detection of these variants and can be cost-prohibitive when applied to large cohorts or to serial sequencing. In this study, an affordable (approximately US $8 per sample), accurate, and scalable sequencing assay for CHIP is introduced and validated. The efficacy of the assay was demonstrated by identifying CHIP mutations in a cohort of 456 individuals with DNA collected at multiple time points in Vanderbilt University's biobank and quantifying clonal expansion rates over time. A total of 101 individuals with CHIP/clonal cytopenia of undetermined significance were identified, and individual-level clonal expansion rate was calculated using the variant allele fraction at both time points. Differences in clonal expansion rate by driver gene were observed, but there was also significant individual-level heterogeneity, emphasizing the multifactorial nature of clonal expansion. Additionally, mutation co-occurrence and clonal competition between multiple driver mutations were explored.


Subject(s)
Clonal Hematopoiesis , Mutation , Humans , Clonal Hematopoiesis/genetics , Male , Female , Aged , Middle Aged , Adult , High-Throughput Nucleotide Sequencing/methods , High-Throughput Nucleotide Sequencing/economics , Cost-Benefit Analysis , Hematopoietic Stem Cells/metabolism , Hematopoietic Stem Cells/cytology , Clonal Evolution/genetics , Aged, 80 and over , Hematopoiesis/genetics
11.
JAMA Netw Open ; 7(3): e243387, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38551564

ABSTRACT

Importance: US Food and Drug Administration-approved medications for alcohol use disorder (MAUD) are significantly underused. Hospitalizations may provide an unmet opportunity to initiate MAUD, but few studies have examined clinical outcomes of patients who initiate these medications at hospital discharge. Objective: To investigate the association between discharge MAUD initiation and 30-day posthospitalization outcomes. Design, Setting, and Participants: This cohort study was conducted among patients with Medicare Part D who had alcohol-related hospitalizations in 2016. Data were analyzed from October 2022 to December 2023. Exposures: Discharge MAUD initiation was defined as oral naltrexone, acamprosate, or disulfiram pharmacy fills within 2 days of discharge. Main outcomes: The primary outcome was a composite of all-cause mortality or return to hospital (emergency department visits and hospital readmissions) within 30 days of discharge. Secondary outcomes included these components separately, return to hospital for alcohol-related diagnoses, and primary care or mental health follow-up within 30 days of discharge. Propensity score 3:1 matching and modified Poisson regressions were used to compare outcomes between patients who received and did not receive discharge MAUD. Results: There were 6794 unique individuals representing 9834 alcohol-related hospitalizations (median [IQR] age, 54 [46-62] years; 3205 hospitalizations among females [32.6%]; 1754 hospitalizations among Black [17.8%], 712 hospitalizations among Hispanic [7.2%], and 7060 hospitalizations among White [71.8%] patients). Of these, 192 hospitalizations (2.0%) involved discharge MAUD initiation. After propensity matching, discharge MAUD initiation was associated with a 42% decreased incidence of the primary outcome (incident rate ratio, 0.58 [95% CI, 0.45 to 0.76]; absolute risk difference, -0.18 [95% CI, -0.26 to -0.11]). These findings were consistent among secondary outcomes (eg, incident rate ratio for all-cause return to hospital, 0.56 [95% CI, 0.43 to 0.73]) except for mortality, which was rare in both groups (incident rate ratio, 3.00 [95% CI, 0.42 to 21.22]). Discharge MAUD initiation was associated with a 51% decreased incidence of alcohol-related return to hospital (incident rate ratio, 0.49 [95% CI, 0.34 to 0.71]; absolute risk difference, -0.15 [95% CI, -0.22 to -0.09]). Conclusion and relevance: In this cohort study, discharge initiation of MAUD after alcohol-related hospitalization was associated with a large absolute reduction in return to hospital within 30 days. These findings support efforts to increase uptake of MAUD initiation at hospital discharge.


Subject(s)
Alcoholism , Patient Discharge , Female , Humans , Aged , United States/epidemiology , Middle Aged , Alcoholism/drug therapy , Alcoholism/epidemiology , Cohort Studies , Medicare , Hospitals
13.
PLoS One ; 19(2): e0297741, 2024.
Article in English | MEDLINE | ID: mdl-38358974

ABSTRACT

Prior to the next generation sequencing and characterization of the tumor genome landscape, mutations in the SWI/SNF chromatin remodeling complex and the KEAP1-NRF2 signaling pathway were underappreciated. While these two classes of mutations appeared to independently contribute to tumor development, recent reports have demonstrated a mechanistic link between these two regulatory mechanisms in specific cancer types and cell models. In this work, we expand upon these data by exploring the relationship between mutations in BAF and PBAF subunits of the SWI/SNF complex and activation of NRF2 signal transduction across many cancer types. ARID1A/B mutations were strongly associated with NRF2 transcriptional activity in head and neck squamous carcinomas (HNSC). Many additional tumor types showed significant association between NRF2 signaling and mutation of specific components of the SWI/SNF complex. Different effects of BAF and PBAF mutations on the polarity of NRF2 signaling were observed. Overall, our results support a context-dependent functional link between SWI/SNF and NRF2 mutations across human cancers and implicate ARID1A inactivation in HPV-negative HNSC in promoting tumor progression and survival through activation of the KEAP1-NRF2 signaling pathway. The tumor-specific effects of these mutations open a new area of study for how mutations in the KEAP1-NRF2 pathway and the SWI/SNF complex contribute to cancer.


Subject(s)
DNA-Binding Proteins , Head and Neck Neoplasms , NF-E2-Related Factor 2 , Transcription Factors , Humans , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Head and Neck Neoplasms/genetics , Kelch-Like ECH-Associated Protein 1/genetics , Kelch-Like ECH-Associated Protein 1/metabolism , Mutation , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Signal Transduction/genetics , Squamous Cell Carcinoma of Head and Neck/genetics , Transcription Factors/genetics , Transcription Factors/metabolism
14.
Nat Commun ; 15(1): 1206, 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38332019

ABSTRACT

Micro-sized silicon anodes can significantly increase the energy density of lithium-ion batteries with low cost. However, the large silicon volume changes during cycling cause cracks for both organic-inorganic interphases and silicon particles. The liquid electrolytes further penetrate the cracked silicon particles and reform the interphases, resulting in huge electrode swelling and quick capacity decay. Here we resolve these challenges by designing a high-voltage electrolyte that forms silicon-phobic interphases with weak bonding to lithium-silicon alloys. The designed electrolyte enables micro-sized silicon anodes (5 µm, 4.1 mAh cm-2) to achieve a Coulombic efficiency of 99.8% and capacity of 2175 mAh g-1 for >250 cycles and enable 100 mAh LiNi0.8Co0.15Al0.05O2 pouch full cells to deliver a high capacity of 172 mAh g-1 for 120 cycles with Coulombic efficiency of >99.9%. The high-voltage electrolytes that are capable of forming silicon-phobic interphases pave new ways for the commercialization of lithium-ion batteries using micro-sized silicon anodes.

15.
Cancer Res Commun ; 4(2): 487-495, 2024 02 21.
Article in English | MEDLINE | ID: mdl-38335300

ABSTRACT

Aberrant activation of the NRF2/NFE2L2 transcription factor commonly occurs in head and neck squamous cell carcinomas (HNSCC). Mouse model studies have shown that NRF2 activation alone does not result in cancer. When combined with classic oncogenes and at the right dose, NRF2 activation promotes tumor initiation and progression. Here we deleted the tumor suppressor genes p16INK4A and p53 (referred to as CP mice), which are commonly lost in human HNSCC, in the presence of a constitutively active NRF2E79Q mutant (CPN mice). NRF2E79Q expression in CPN mice resulted in squamous cell hyperplasia or dysplasia with hyperkeratosis in the esophagus, oropharynx, and forestomach. In addition, CPN mice displayed oral cavity squamous cell carcinoma (OSCC); CP mice bearing wild-type NRF2 expression did not develop oral cavity hyperplasia, dysplasia or OSCC. In both CP and CPN mice, we also observed predominantly abdominal sarcomas and carcinomas. Our data show that in the context of p53 and p16 tumor suppressor loss, NRF2 activation serves oncogenic functions to drive OSCC. CPN mice represent a new model for OSCC that closely reflects the genetics of human HNSCC. SIGNIFICANCE: Human squamous cancers frequently show constitutive NRF2 activation, associated with poorer outcomes and resistance to multiple therapies. Here, we report the first activated NRF2-driven and human-relevant mouse model of squamous cell carcinoma that develops in the background of p16 and p53 loss. The availability of this model will lead to a clearer understanding of how NRF2 contributes to the initiation, progression, and therapeutic response of OSCC.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Animals , Humans , Mice , Carcinoma, Squamous Cell/genetics , Disease Models, Animal , Head and Neck Neoplasms/genetics , Hyperplasia/genetics , Mouth Neoplasms/genetics , NF-E2-Related Factor 2/genetics , Squamous Cell Carcinoma of Head and Neck/genetics , Tumor Suppressor Protein p53/genetics , Cyclin-Dependent Kinase Inhibitor p16/metabolism
16.
Subst Use Addctn J ; 45(2): 268-277, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38258838

ABSTRACT

BACKGROUND: Homeless-tailored office-based opioid treatment (OBOT) programs have been developed to address the ongoing opioid overdose crisis, which disproportionately affects people experiencing homelessness. The objective of this study was to evaluate the facilitators of and barriers to retention in a homeless-tailored OBOT program. METHODS: We performed in-depth qualitative interviews with 24 homeless-experienced adults who newly enrolled in Boston Health Care for the Homeless Program's OBOT program from January 6, 2022 through January 5, 2023. We purposively sampled participants based on whether they were retained at 1 month (n = 12) or not (n = 12). We used an abductive analytic process, applying codes to the interview transcripts from an a priori analytic framework based on the Behavioral Model for Vulnerable Populations and supplementing with emergent codes as needed. We compared themes by participants' 1-month retention status to explore facilitators of and barriers to retention in OBOT care. RESULTS: The average age was 41.9 years, 29.2% were female, 20.8% were Black, 58.3% were White, and 33.0% were Hispanic. Facilitators of retention common to many participants included the clinic experience, low-threshold model, clinic staff, and provision of comprehensive care. Among participants who were retained at 1-month, personal motivation, use of extended-release buprenorphine, and adequate buprenorphine efficacy were additional facilitators. Barriers to retention common to many participants included the clinic's surrounding environment, competing subsistence difficulties, and transportation difficulty. Among participants who were not retained at 1-month, opioid use severity, drug use in social networks, and inadequate buprenorphine efficacy represented additional barriers. CONCLUSIONS: We identified several common determinants of OBOT retention among our homeless-experienced participants as well as some facilitators and barriers that differed by 1-month retention status. These divergent factors represent potential points of intervention to promote retention in homeless-tailored OBOT programs.


Subject(s)
Buprenorphine , Ill-Housed Persons , Adult , Humans , Female , Male , Analgesics, Opioid/therapeutic use , Outpatients , Opiate Substitution Treatment
17.
Ann Biomed Eng ; 52(3): 638-646, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38062312

ABSTRACT

We demonstrate a methodology which both improves oxygen transport and reduces or eliminates bubble formation in a novel hyperbaric membrane oxygenator catheter model system. Angular oscillations were introduced to a bundle of hollow fiber membranes (HFMs) supplied with hyperbaric 100% oxygen at average gauge pressures up to 0.35 barg. Oscillating bundles enabled delivery of an oxygen flux of up to 400 mL min-1 m-2 in an aqueous solution, a doubling over a previous non-oscillating setup. Similarly, the addition of angular oscillations facilitated a five-fold reduction in pressure to achieve similar oxygen flux. The increased angular speed of oscillation improved flux, while the addition of angular micro-oscillation variations resulted in flux reductions of 7-20% compared to continuous macro-oscillation only, depending on mixing conditions. However, semi-quantitative visual observation demonstrated that angular oscillations reduced or eliminated the instance of oxygen bubble formation on the HFMs. The modeled mass transfer coefficients indicated a quasi linear relationship between rotational velocity and flux, suggesting that faster oscillation speeds could further improve oxygen mass transport allowing for HFM bundles to maintain high oxygen fluxes while eliminating bubble formation. This encourages further development of our compact oxygenating catheter that could be used intravascularly.


Subject(s)
Oxygen , Oxygenators , Catheters , Equipment Design , Oxygenators, Membrane
18.
medRxiv ; 2023 Nov 09.
Article in English | MEDLINE | ID: mdl-37986782

ABSTRACT

Clonal hematopoiesis of indeterminate potential (CHIP) is a common age-related phenomenon that occurs when hematopoietic stem cells acquire mutations in a select set of genes commonly mutated in myeloid neoplasia which then expand clonally. Current sequencing assays to detect CHIP are not optimized for the detection of these variants and can be cost-prohibitive when applied to large cohorts or serial sequencing. Here, we present and validate a CHIP targeted sequencing assay that is affordable (∼$8/sample), accurate and highly scalable. To demonstrate the utility of this assay, we detected CHIP in a cohort of 456 individuals with DNA collected at multiple timepoints in the Vanderbilt BioVU biobank and quantified clonal expansion rates over time. A total of 101 individuals with CHIP were identified, and individual-level clonal expansion rate was calculated using the variant allele fraction (VAF) at both timepoints. Differences in clonal expansion rate by driver gene were observed, but there was also significant individual-level heterogeneity, emphasizing the multifactorial nature of clonal expansion. We further describe the mutation co-occurrence and clonal competition between multiple driver mutations.

19.
JAMA ; 330(15): 1488-1490, 2023 10 17.
Article in English | MEDLINE | ID: mdl-37707800

ABSTRACT

This study uses data from the 2013­March 2020 National Health and Nutrition Examination Survey to assess contemporary patterns of risky alcohol use among adults taking high-risk alcohol-interactive medications (benzodiazepine receptor agonists, opioids, and antiepileptics).


Subject(s)
Alcohol Deterrents , Alcohol Drinking , Drug Interactions , Alcohol Drinking/epidemiology , Risk-Taking , Health Risk Behaviors , Humans , Adult , United States/epidemiology , Alcohol Deterrents/classification , Alcohol Deterrents/pharmacology , Alcohol Deterrents/therapeutic use , Chronic Disease
20.
Transl Androl Urol ; 12(8): 1326-1335, 2023 Aug 31.
Article in English | MEDLINE | ID: mdl-37680230

ABSTRACT

Placement of an inflatable penile prosthesis (IPP) in a transgender patient's neophallus carries unique considerations versus cis-gender IPP placement in mitigating infection, erosion, and overall complication rates. An example of this includes the lack of an anatomical corpus cavernosum and crura for cylinder placement and anchoring. Multiple grafting approaches and materials have been utilized to mitigate possible cylinder instability and improve anchoring. Here we describe our experience and surgical technique in IPP neophallus placement utilizing a single cylinder with distal and proximal cylinder human cadaver pericardium (Tutoplast®, IOP Ophthalmics, Costa Mesa, CA, USA) grafts. Our goals were to determine postoperative satisfaction and device functionality in patients undergoing transgender neophallus IPP placement using our technique. Both patients report satisfaction and no complications at last follow-up (currently up to 14 and 23 months post-operatively, respectively) with satisfactory erectile function and ability to perform penetrative intercourse. In neophallus IPP placement, the anatomical differences compared to cis-gender IPP operations require unique considerations such as cylinder grafting material selection for proximal cylinder fixation and mitigation of device erosion rates. Optimization of grafting material in neophallus IPP placement in an effort to reduce erosion rates has become increasingly important as frequency of this operation increases. Utilizing human cadaver pericardium graft in distal and proximal cylinder coverage shows beneficial preliminary outcomes in our patients.

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