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1.
Sci Rep ; 14(1): 11590, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773178

ABSTRACT

Human interaction is immersed in laughter; though genuine and posed laughter are acoustically distinct, they are both crucial socio-emotional signals. In this novel study, autistic and non-autistic adults explicitly rated the affective properties of genuine and posed laughter. Additionally, we explored whether their self-reported everyday experiences with laughter differ. Both groups could differentiate between these two types of laughter. However, autistic adults rated posed laughter as more authentic and emotionally arousing than non-autistic adults, perceiving it to be similar to genuine laughter. Autistic adults reported laughing less, deriving less enjoyment from laughter, and experiencing difficulty in understanding the social meaning of other people's laughter compared to non-autistic people. Despite these differences, autistic adults reported using laughter socially as often as non-autistic adults, leveraging it to mediate social contexts. Our findings suggest that autistic adults show subtle differences in their perception of laughter, which may be associated with their struggles in comprehending the social meaning of laughter, as well as their diminished frequency and enjoyment of laughter in everyday scenarios. By combining experimental evidence with first-person experiences, this study suggests that autistic adults likely employ different strategies to understand laughter in everyday contexts, potentially leaving them socially vulnerable in communication.


Subject(s)
Autistic Disorder , Laughter , Humans , Laughter/psychology , Male , Adult , Female , Autistic Disorder/psychology , Autistic Disorder/physiopathology , Young Adult , Emotions/physiology , Middle Aged
2.
Cereb Cortex ; 34(5)2024 May 02.
Article in English | MEDLINE | ID: mdl-38752979

ABSTRACT

Spontaneous and conversational laughter are important socio-emotional communicative signals. Neuroimaging findings suggest that non-autistic people engage in mentalizing to understand the meaning behind conversational laughter. Autistic people may thus face specific challenges in processing conversational laughter, due to their mentalizing difficulties. Using fMRI, we explored neural differences during implicit processing of these two types of laughter. Autistic and non-autistic adults passively listened to funny words, followed by spontaneous laughter, conversational laughter, or noise-vocoded vocalizations. Behaviourally, words plus spontaneous laughter were rated as funnier than words plus conversational laughter, and the groups did not differ. However, neuroimaging results showed that non-autistic adults exhibited greater medial prefrontal cortex activation while listening to words plus conversational laughter, than words plus genuine laughter, while autistic adults showed no difference in medial prefrontal cortex activity between these two laughter types. Our findings suggest a crucial role for the medial prefrontal cortex in understanding socio-emotionally ambiguous laughter via mentalizing. Our study also highlights the possibility that autistic people may face challenges in understanding the essence of the laughter we frequently encounter in everyday life, especially in processing conversational laughter that carries complex meaning and social ambiguity, potentially leading to social vulnerability. Therefore, we advocate for clearer communication with autistic people.


Subject(s)
Autistic Disorder , Brain Mapping , Brain , Laughter , Magnetic Resonance Imaging , Humans , Laughter/physiology , Laughter/psychology , Male , Female , Adult , Autistic Disorder/physiopathology , Autistic Disorder/diagnostic imaging , Autistic Disorder/psychology , Young Adult , Brain/diagnostic imaging , Brain/physiopathology , Brain/physiology , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/physiopathology , Prefrontal Cortex/physiology , Acoustic Stimulation
3.
Inj Prev ; 2024 May 06.
Article in English | MEDLINE | ID: mdl-38719440

ABSTRACT

BACKGROUND: State opioid prescribing cap laws, mandatory prescription drug monitoring programme query or enrolment laws and pill mill laws have been implemented across US states to curb high-risk opioid prescribing. Previous studies have measured the impact of these laws on opioid use and overdose death, but no prior work has measured the impact of these laws on fatal crashes in a multistate analysis. METHODS: To study the association between state opioid prescribing laws and fatal crashes, 13 treatment states that implemented a single law of interest in a 4-year period were identified, together with unique groups of control states for each treatment state. Augmented synthetic control analyses were used to estimate the association between each state law and the overall rate of fatal crashes, and the rate of opioid-involved fatal crashes, per 100 000 licensed drivers in the state. Fatal crash data came from the Fatality Analysis Reporting System. RESULTS: Results of augmented synthetic control analyses showed small-in-magnitude, non-statistically significant changes in all fatal crash outcomes attributable to the 13 state opioid prescribing laws. While non-statistically significant, results attributable to the laws varied in either direction-from an increase of 0.14 (95% CI, -0.32 to 0.60) fatal crashes per 100 000 licensed drivers attributable to Ohio's opioid prescribing cap law, to a decrease of 0.30 (95% CI, -1.17 to 0.57) fatal crashes/100 000 licensed drivers attributable to Mississippi's pill mill law. CONCLUSION: These findings suggest that state-level opioid prescribing laws are insufficient to help address rising rates of fatally injured drivers who test positive for opioids. Other options will be needed to address this continuing injury problem.

4.
Health Aff Sch ; 2(3): qxae024, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38756918

ABSTRACT

Offering patients medications for opioid use disorder (MOUD) is the standard of care for opioid use disorder (OUD), but an estimated 75%-90% of people with OUD who could benefit from MOUD do not receive medication. Payment policy, defined as public and private payers' approaches to covering and reimbursing providers for MOUD, is 1 contributor to this treatment gap. We conducted a policy analysis and qualitative interviews (n = 21) and surveys (n = 31) with US MOUD payment policy experts to characterize MOUD insurance coverage across major categories of US insurers and identify opportunities for reform and innovation. Traditional Medicare, Medicare Advantage, and Medicaid all provide coverage for at least 1 formulation of buprenorphine, naltrexone, and methadone for OUD. Private insurance coverage varies by carrier and by plan, with methadone most likely to be excluded. The experts interviewed cautioned against rigid reimbursement models that force patients into one-size-fits-all care and endorsed future development and adoption of value-based MOUD payment models. More than 70% of experts surveyed reported that Medicare, Medicaid, and private insurers should increase payment for office- and opioid treatment program-based MOUD. Validation of MOUD performance metrics is needed to support future value-based initiatives.

6.
Patient Educ Couns ; 125: 108289, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38631197

ABSTRACT

OBJECTIVES: This study explores patient perspectives (ideas, concerns, and expectations) in surgeon-patient consultations. METHODS: We examined 54 video-recorded consultations using applied conversation analysis. Consultations took place from 2012 to 2017 in an Australian metropolitan hospital clinic centre and involved seven surgeons across six specialties. RESULTS: Patient perspectives emerged in less than one third of consultations. We describe the initiation of and response to potential perspectives sequences, demonstrating how patients and surgeons co-construct these sequences when they do occur. CONCLUSIONS: Findings suggest a need for greater attention to supporting patient agency through explicit pursuit of patient perspectives. The implications extend to the Calgary-Cambridge Guide, suggesting that it may benefit from a focus on active pursuit and appropriate responsiveness to patient perspectives. PRACTICE IMPLICATIONS: This study highlights the need for surgeons to actively engage with the patient perspective offered in consultations, emphasising the importance of respect for the patient's knowledge and expectations to improve patient satisfaction and healthcare outcomes.

7.
Cortex ; 174: 110-124, 2024 May.
Article in English | MEDLINE | ID: mdl-38502976

ABSTRACT

BACKGROUND: Gaze following difficulties are considered an early marker of autism, thought likely to cumulatively impact the development of social cognition, language and social skills. Subtle differences in gaze following abilities may contribute to the diverse range social and communicative autistic characteristics observed across people with genetic syndromes, such as Cornelia de Lange (CdLS) and fragile X (FXS) syndromes. AIMS: To compare profiles of 1) visual attention to the eye region at critical points of the attention direction process, 2) whether children follow the gaze cue to the object, and 3) participant looking time to the target object following the gaze cue between groups and conditions. MATERIALS AND METHODS: Children with CdLS (N = 11) and FXS (N = 8) and autistic (N = 22) and neurotypical (N = 15) children took part in a passive viewing paradigm adapted from Senju and Csibra (2008), in which videos of a central cue (ball/cartoon face/human face) directed attention towards one of two objects. Visual attention patterns were recorded via eye tracking technology. RESULTS: Neurotypical children were used as a reference group against which the autistic, CdLS and FXS groups were compared. Although autistic children looked at the eye region for significantly less time, they looked at the target object as frequently and for a similar duration as neurotypical children. Children with FXS looked at the target as frequently as neurotypical children but looked at it for comparatively less time. Both neurotypical children and children with CdLS frequently looked at the eye region, but children with CdLS were less likely to look at the target than neurotypical children. CONCLUSIONS: Findings provide preliminary evidence of unique patterns of visual attention and gaze following strategies in children with CdLS, children with FXS and autistic children. These unique gaze following patterns may underpin the distinct profiles of social and communication autistic traits observed between these groups.


Subject(s)
Autistic Disorder , De Lange Syndrome , Fragile X Syndrome , Child , Humans , Communication , Language
8.
Cancers (Basel) ; 16(5)2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38473255

ABSTRACT

Background: There is growing awareness of breast density in women attending breast cancer screening; however, it is unclear whether this awareness is associated with increased knowledge. This study aims to evaluate breast density knowledge among Australian women attending breast cancer screening. Method: This cross-sectional study was conducted on women undergoing breast cancer screening at The Queen Elizabeth Hospital Breast/Endocrine outpatient department. Participants were provided with a questionnaire to assess knowledge, awareness, and desire to know their own breast density. Result: Of the 350 women who participated, 61% were familiar with 'breast density' and 57% had 'some knowledge'. Prior breast density notification (OR = 4.99, 95% CI = 2.76, 9.03; p = 0.004), awareness (OR = 4.05, 95% CI = 2.57, 6.39; p = 0.004), younger age (OR = 0.97, 95% CI = 0.96, 0.99; p = 0.02), and English as the language spoken at home (OR = 3.29, 95% CI = 1.23, 8.77; p = 0.02) were independent predictors of 'some knowledge' of breast density. A significant proportion of participants (82%) expressed desire to ascertain their individual breast density. Conclusions: While knowledge of breast density in this Australian cohort is generally quite low, we have identified factors associated with increased knowledge. Further research is required to determine optimal interventions to increase breast density knowledge.

9.
Eur J Clin Nutr ; 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38454153

ABSTRACT

BACKGROUND: The precision of digital anthropometry through 3-dimensional (3D) scanning has been established for relatively large, expensive, non-portable systems. The comparative performance of modern mobile applications is unclear. SUBJECTS/METHODS: Forty-six adults (age: 23.3 ± 5.3 y; BMI: 24.4 ± 4.1 kg/m2) were assessed in duplicate using: (1) a mobile phone application capturing two individual 2D images, (2) a mobile phone application capturing serial images collected during a subject's complete rotation, (3) a traditional scanner with a time of flight infrared sensor collecting visual data from a subject being rotated on a mechanical turntable, and (4) a commercial measuring booth with structured light technology using 20 infrared depth sensors positioned in the booth. The absolute and relative technical error of measurement (TEM) and intraclass correlation coefficient (ICC) for each method were established. RESULTS: Averaged across circumferences, the absolute TEM, relative TEM, and ICC were (1) 0.9 cm, 1.5%, and 0.975; (2) 0.5 cm, 0.9%, and 0.986; (3) 0.8 cm, 1.5%, and 0.974; and (4) 0.6 cm, 1.1%, and 0.985. For total body volume, these values were (1) 2.2 L, 3.0%, and 0.978; (2) 0.8 L, 1.1%, and 0.997; (3) 0.7 L, 0.9%, and 0.998; and (4) 0.8 L, 1.1%, and 0.996, with segmental volumes demonstrating higher relative errors. CONCLUSION: A 3D scanning mobile phone application involving full rotation of subjects in front of a smartphone camera exhibited similar reliability to larger, less portable, more expensive 3D scanners. In contrast, larger errors were observed for a mobile scanning application utilizing two 2D images, although the technical errors were acceptable for some applications.

10.
Health Aff Sch ; 2(2): qxae007, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38344412

ABSTRACT

To mitigate pandemic-related disruptions to addiction treatment, US federal and state governments made significant changes to policies regulating treatment delivery. State health agencies played a key role in implementing these policies, giving agency leaders a distinct vantage point on the feasibility and implications of post-pandemic policy sustainment. We interviewed 46 state health agency and other leaders responsible for implementing COVID-19 addiction treatment policies across 8 states with the highest COVID-19 death rate in their census region. Semi-structured interviews were conducted from April through October 2022. Transcripts were analyzed using summative content analysis to characterize policies that interviewees perceived would, if sustained, benefit addiction treatment delivery long-term. State policies were then characterized through legal database queries, internet searches, and analysis of existing policy databases. State leaders viewed multiple pandemic-era policies as useful for expanding addiction treatment access post-pandemic, including relaxing restrictions for telehealth, particularly for buprenorphine induction and audio-only treatment; take-home methadone allowances; mobile methadone clinics; and out-of-state licensing flexibilities. All states adopted at least 1 of these policies during the pandemic. Future research should evaluate these policies outside of the acute COVID-19 pandemic context.

11.
Water Sci Technol ; 89(3): 588-602, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38358491

ABSTRACT

Understanding nutrient cycling patterns in plants deployed within constructed floating wetlands (CFWs) is critical for improving CFWs' design and management practices. This study evaluated phosphorus (P) uptake and release patterns during fall/winter plant senescence and spring regrowth. Two mesocosm-scale CFW experiments were conducted characterizing plant growth, plant tissue P levels, and water quality (nutrients and phytoplankton). Experiment 1 quantified P uptake during spring regrowth after overwintering, and experiment 2 quantified P release during fall senescence. Plant treatments (CFWs with Pontederia cordata or Juncus effusus) were compared to an open-water control. In spring, J. effusus removed 0.056 g P m-2 d-1 (19.4% of the load), P. cordata removed 0.034 g P m-2 d-1 (10%), and the open-water control removed 0.03 g P m-2 d-1 (10%). In fall, J. effusus fixed 0.008 g P m-2 d-1 (2.1% of the load), P. cordata released 0.014 g P m-2 d-1 (-2.1%), and controls fixed 0.023 g P m-2 d-1 (6.3%). P was consistently released during the fall experiment and occasionally released in the spring experiment, likely from senescing plant tissues (fall) and from roots sloughing after new root growth (spring). Results demonstrate the potential for multi-season deployment of CFWs using J. effusus for reducing P loads year-round.


Subject(s)
Nutrients , Wetlands , Phosphorus , Phytoplankton , Plant Development
12.
BMC Cancer ; 24(1): 201, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38350888

ABSTRACT

BACKGROUND: For patients with liver-confined metastatic colorectal cancer (mCRC), local therapy of isolated metastases has been associated with long-term progression-free and overall survival (OS). However, for patients with more advanced mCRC, including those with extrahepatic disease, the efficacy of local therapy is less clear although increasingly being used in clinical practice. Prospective studies to clarify the role of metastatic-directed therapies in patients with mCRC are needed. METHODS: The Evaluating Radiation, Ablation, and Surgery (ERASur) A022101/NRG-GI009 trial is a randomized, National Cancer Institute-sponsored phase III study evaluating if the addition of metastatic-directed therapy to standard of care systemic therapy improves OS in patients with newly diagnosed limited mCRC. Eligible patients require a pathologic diagnosis of CRC, have BRAF wild-type and microsatellite stable disease, and have 4 or fewer sites of metastatic disease identified on baseline imaging. Liver-only metastatic disease is not permitted. All metastatic lesions must be amenable to total ablative therapy (TAT), which includes surgical resection, microwave ablation, and/or stereotactic ablative body radiotherapy (SABR) with SABR required for at least one lesion. Patients without overt disease progression after 16-26 weeks of first-line systemic therapy will be randomized 1:1 to continuation of systemic therapy with or without TAT. The trial activated through the Cancer Trials Support Unit on January 10, 2023. The primary endpoint is OS. Secondary endpoints include event-free survival, adverse events profile, and time to local recurrence with exploratory biomarker analyses. This study requires a total of 346 evaluable patients to provide 80% power with a one-sided alpha of 0.05 to detect an improvement in OS from a median of 26 months in the control arm to 37 months in the experimental arm with a hazard ratio of 0.7. The trial uses a group sequential design with two interim analyses for futility. DISCUSSION: The ERASur trial employs a pragmatic interventional design to test the efficacy and safety of adding multimodality TAT to standard of care systemic therapy in patients with limited mCRC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05673148, registered December 21, 2022.


Subject(s)
Colonic Neoplasms , Liver Neoplasms , Radiosurgery , Rectal Neoplasms , Humans , Prospective Studies , Radiosurgery/methods , Liver Neoplasms/therapy
13.
Cortex ; 173: 150-160, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38402659

ABSTRACT

Autistic adults struggle to reliably differentiate genuine and posed smiles. Intergroup bias is a promising factor that may modulate smile discrimination performance, which has been shown in neurotypical adults, and which could highlight ways to make social interactions easier. However, it is not clear whether this bias also exists in autistic people. Thus, the current study aimed to investigate this in autism using a minimal group paradigm. Seventy-five autistic and sixty-one non-autistic adults viewed videos of people making genuine or posed smiles and were informed (falsely) that some of the actors were from an in-group and others were from an out-group. The ability to identify smile authenticity of in-group and out-group members and group identification were assessed. Our results revealed that both groups seemed equally susceptible to ingroup favouritism, rating ingroup members as more genuine, but autistic adults also generally rated smiles as less genuine and were less likely to identify with ingroup members. Autistic adults showed reduced sensitivity to the different smile types but the absence of an intergroup bias in smile discrimination in both groups seems to indicate that membership can only modulate social judgements but not social abilities. These findings suggest a reconsideration of past findings that might have misrepresented the social judgements of autistic people through introducing an outgroup disadvantage, but also a need for tailored support for autistic social differences that emphasizes similarity and inclusion between diverse people.


Subject(s)
Autistic Disorder , Adult , Humans , Social Skills , Social Perception , Smiling , Group Processes
14.
Sci Rep ; 14(1): 4697, 2024 02 26.
Article in English | MEDLINE | ID: mdl-38409351

ABSTRACT

One promising account for autism is implicit mentalizing difficulties. However, this account and even the existence of implicit mentalizing have been challenged because the replication results are mixed. Those unsuccessful replications may be due to the task contexts not being sufficiently evaluative. Therefore, the current study developed a more evaluative paradigm by implementing a prompt question. This was assessed in 60 non-autistic adults and compared with a non-prompt version. Additionally, parents of autistic children are thought to show a genetic liability to autistic traits and cognition and often report mental health problems, but the broader autism phenotype (BAP) is an under-researched area. Thus, we also aimed to compare 33 BAP and 26 non-BAP mothers on mentalizing abilities, autistic traits, compensation and mental health. Our results revealed that more evaluative contexts can facilitate implicit mentalizing in BAP and non-BAP populations, and thus improve task reliability and replicability. Surprisingly, BAP mothers showed better implicit mentalizing but worse mental health than non-BAP mothers, which indicates the heterogeneity in the broader autism phenotype and the need to promote BAP mothers' psychological resilience. The findings underscore the importance of contexts for implicit mentalizing and the need to profile mentalizing and mental health in BAP parents.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Mentalization , Female , Child , Adult , Humans , Autistic Disorder/genetics , Mental Health , Reproducibility of Results , Phenotype , Autism Spectrum Disorder/psychology
16.
Health Commun ; : 1-12, 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38177980

ABSTRACT

Doctors running late may convey a lack of respect which can impair the therapeutic relationship. This study examines how surgeons address lateness in consultations with patients. We analyzed 52 consultation recordings from a range of surgical specialties in an Australian metropolitan setting. Conversation analysis was used to analyze interactional sequences where lateness was addressed. Six sequences were identified within four recordings. The two consultations with two apologies include a surgeon and registrar apologizing in a neurosurgical consultation and a surgeon apologizing twice within a colorectal consultation. Apologies were either accepted or responded to with an account for not accepting the apology. When these accounts were made, consultations could only progress when patients accepted an explanation for lateness or the degree of complainability about lateness was reduced. The infrequent occurrence of apologies for lateness, and the way in which these sequences unfolded when they did occur, suggest that there is greater acceptability of lateness for surgeons than in ordinary social situations.

17.
Am J Hum Genet ; 111(1): 11-23, 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38181729

ABSTRACT

Precision medicine initiatives across the globe have led to a revolution of repositories linking large-scale genomic data with electronic health records, enabling genomic analyses across the entire phenome. Many of these initiatives focus solely on research insights, leading to limited direct benefit to patients. We describe the biobank at the Colorado Center for Personalized Medicine (CCPM Biobank) that was jointly developed by the University of Colorado Anschutz Medical Campus and UCHealth to serve as a unique, dual-purpose research and clinical resource accelerating personalized medicine. This living resource currently has more than 200,000 participants with ongoing recruitment. We highlight the clinical, laboratory, regulatory, and HIPAA-compliant informatics infrastructure along with our stakeholder engagement, consent, recontact, and participant engagement strategies. We characterize aspects of genetic and geographic diversity unique to the Rocky Mountain region, the primary catchment area for CCPM Biobank participants. We leverage linked health and demographic information of the CCPM Biobank participant population to demonstrate the utility of the CCPM Biobank to replicate complex trait associations in the first 33,674 genotyped individuals across multiple disease domains. Finally, we describe our current efforts toward return of clinical genetic test results, including high-impact pathogenic variants and pharmacogenetic information, and our broader goals as the CCPM Biobank continues to grow. Bringing clinical and research interests together fosters unique clinical and translational questions that can be addressed from the large EHR-linked CCPM Biobank resource within a HIPAA- and CLIA-certified environment.


Subject(s)
Learning Health System , Precision Medicine , Humans , Biological Specimen Banks , Colorado , Genomics
18.
Aust N Z J Psychiatry ; 58(3): 260-276, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37353970

ABSTRACT

OBJECTIVE: The aim of this study was to test the effectiveness of a tailored quitline tobacco treatment ('Quitlink') among people receiving support for mental health conditions. METHODS: We employed a prospective, cluster-randomised, open, blinded endpoint design to compare a control condition to our 'Quitlink' intervention. Both conditions received a brief intervention delivered by a peer researcher. Control participants received no further intervention. Quitlink participants were referred to a tailored 8-week quitline intervention delivered by dedicated Quitline counsellors plus combination nicotine replacement therapy. The primary outcome was self-reported 6 months continuous abstinence from end of treatment (8 months from baseline). Secondary outcomes included additional smoking outcomes, mental health symptoms, substance use and quality of life. A within-trial economic evaluation was conducted. RESULTS: In total, 110 participants were recruited over 26 months and 91 had confirmed outcomes at 8 months post baseline. There was a difference in self-reported prolonged abstinence at 8-month follow-up between Quitlink (16%, n = 6) and control (2%, n = 1) conditions, which was not statistically significant (OR = 8.33 [0.52, 132.09] p = 0.131 available case). There was a significant difference in favour of the Quitlink condition on 7-day point prevalence at 2 months (OR = 8.06 [1.27, 51.00] p = 0.027 available case). Quitlink costs AU$9231 per additional quit achieved. CONCLUSION: The Quitlink intervention did not result in significantly higher rates of prolonged abstinence at 8 months post baseline. However, engagement rates and satisfaction with the 'Quitlink' intervention were high. While underpowered, the Quitlink intervention shows promise. A powered trial to determine its effectiveness for improving long-term cessation is warranted.


Subject(s)
Mental Health Services , Smoking Cessation , Humans , Smoking Cessation/psychology , Quality of Life , Prospective Studies , Tobacco Use Cessation Devices , Referral and Consultation
19.
Br J Pharmacol ; 181(5): 698-711, 2024 03.
Article in English | MEDLINE | ID: mdl-37740611

ABSTRACT

BACKGROUND AND PURPOSE: 11ß-Hydroxysteroid dehydrogenase-1 (11ß-HSD1) catalyses the oxoreduction of cortisone to cortisol, amplifying levels of active glucocorticoids. It is a pharmaceutical target in metabolic disease and cognitive impairments. 11ß-HSD1 also converts some 7oxo-steroids to their 7ß-hydroxy forms. A recent study in mice described the ratio of tauroursodeoxycholic acid (TUDCA)/tauro-7oxolithocholic acid (T7oxoLCA) as a biomarker for decreased 11ß-HSD1 activity. The present study evaluates the equivalent bile acid ratio of glycoursodeoxycholic acid (GUDCA)/glyco-7oxolithocholic acid (G7oxoLCA) as a biomarker for pharmacological 11ß-HSD1 inhibition in humans and compares it with the currently applied urinary (5α-tetrahydrocortisol + tetrahydrocortisol)/tetrahydrocortisone ((5αTHF + THF)/THE) ratio. EXPERIMENTAL APPROACH: Bile acid profiles were analysed by ultra-HPLC tandem-MS in blood samples from two independent, double-blind placebo-controlled clinical studies of the orally administered selective 11ß-HSD1 inhibitor AZD4017. The blood GUDCA/G7oxoLCA ratio was compared with the urinary tetrahydro-glucocorticoid ratio for ability to detect 11ß-HSD1 inhibition. KEY RESULTS: No significant alterations were observed in bile acid profiles following 11ß-HSD1 inhibition by AZD4017, except for an increase of the secondary bile acid G7oxoLCA. The enzyme product/substrate ratio GUDCA/G7oxoLCA was found to be more reliable to detect 11ß-HSD1 inhibition than the absolute G7oxoLCA concentration in both cohorts. Comparison of the blood GUDCA/G7oxoLCA ratio with the urinary (5αTHF + THF)/THE ratio revealed that both successfully detect 11ß-HSD1 inhibition. CONCLUSIONS AND IMPLICATIONS: 11ß-HSD1 inhibition does not cause major alterations in bile acid homeostasis. The GUDCA/G7oxoLCA ratio represents the first blood biomarker of pharmacological 11ß-HSD1 inhibition and may replace or complement the urinary (5αTHF + THF)/THE ratio biomarker.


Subject(s)
11-beta-Hydroxysteroid Dehydrogenase Type 1 , Glucocorticoids , Animals , Humans , Mice , Bile Acids and Salts , Biomarkers , Glucocorticoids/metabolism , Hydrocortisone/metabolism , Tetrahydrocortisol
20.
Psychiatr Serv ; 75(1): 72-75, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37461819

ABSTRACT

OBJECTIVE: The authors examined trends in opioid use disorder treatment and in-person and telehealth modalities before and after COVID-19 pandemic onset among patients who had received treatment prepandemic. METHODS: The sample included 13,113 adults with commercial insurance or Medicare Advantage and receiving opioid use disorder treatment between March 2018 and February 2019. Trends in opioid use disorder outpatient treatment, treatment with medications for opioid use disorder (MOUD), and in-person and telehealth modalities were examined 1 year before pandemic onset and 2 years after (March 2019-February 2022). RESULTS: From March 2019 to February 2022, the proportion of patients with opioid use disorder outpatient and MOUD visits declined by 2.8 and 0.3 percentage points, respectively. Prepandemic, 98.6% of outpatient visits were in person; after pandemic onset, at least 34.9% of patients received outpatient care via telehealth. CONCLUSIONS: Disruptions in opioid use disorder outpatient and MOUD treatments were marginal during the pandemic, possibly because of increased telehealth utilization.


Subject(s)
COVID-19 , Medicare Part C , Opioid-Related Disorders , Telemedicine , Aged , United States/epidemiology , Adult , Humans , Outpatients , Pandemics , Opioid-Related Disorders/drug therapy , Opioid-Related Disorders/epidemiology
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