Hyperpolarized 15N caffeine, a potential probe of liver function and perfusion.

PURPOSE: To demonstrate hyperpolarization of 15N-caffeine and report exploratory findings as a potential probe of liver function and perfusion. METHODS: An amorphous formulation of [1,3-15N2]caffeine was developed for hyperpolarization via dissolution dynamic nuclear polarization. Polarizer hardware was augmented to support monitoring of solid-state 15N MR signals during the buildup of hyperpolarization. Liquid state hyperpolarized 15N MR signals were obtained in a preclinical 3T magnet by interfacing an external spectrometer console with home-built RF surface coils. 15N signal decay constants were estimated in H2O and in vivo in liver and brain regions of rats at 3 T. Decays were also measured at 9.4 T to assess the effect of B0, and in the presence of albumin to assess the impact of protein binding. RESULTS: Polarization levels of 3.5% and aqueous T1 relaxation times of nearly 200 s were attained for both N1 and N3 positions at 3 T. Shorter apparent decay constants were observed in vivo, ranging from 25 s to 43 s, with modest extensions possible by exploiting competitive binding of iophenoxate with plasma albumin. Downstream products of caffeine could not be detected on in vivo 15N-MR spectra of the liver region, even with metabolic stimulation by ß $$ \beta $$ -naphthoflavone treatment. Considering the high perfusion rate of brain, persistence of caffeine signal in this region is consistent with potential value as a perfusion imaging agent. CONCLUSION: These results establish the feasibility of hyperpolarization of hyperpolarized 15N-caffeine, but further work is necessary to establish the role of this new agent to probe liver metabolism and perfusion.

A vendor-neutral EPI sequence for hyperpolarized 13C MRI.

PURPOSE: To develop a flexible, vendor-neutral EPI sequence for hyperpolarized 13C metabolic imaging. METHODS: An open-source EPI sequence consisting of a metabolite-specific spectral-spatial RF excitation pulse and a customizable EPI readout was created using the Pulseq framework. To explore the flexibility of our sequence, we tested several versions of the sequence including a symmetric 3D readout with different spatial resolutions for each metabolite (1.0 cm3 and 1.5 cm3). A multichamber phantom constructed with a Shepp-Logan geometry, containing two chambers filled with either natural abundance 13C compounds or hyperpolarized (HP) [1-13C]pyruvate, was used to test each sequence. For experiments involving HP [1-13C]pyruvate, a single chamber was prefilled with nicotinamide adenine dinucleotide hydride and lactate dehydrogenase to facilitate the conversion of [1-13C]pyruvate to [1-13C]lactate. All experiments were performed on a Siemens Prisma 3T scanner. RESULTS: All the sequence variations localized natural-abundance 13C ethylene glycol and methanol to the appropriate compartment of the multichamber phantom. [1-13C]pyruvate was detectable in both chambers following the injection of HP [1-13C]pyruvate, whereas [1-13C]lactate was only found in the chamber containing nicotinamide adenine dinucleotide hydride and lactate dehydrogenase. The conversion rate from [1-13C]pyruvate to [1-13C]lactate (kPL) was 0.01 s-1 (95% confidence interval [0.00, 0.02]). CONCLUSION: We have developed and tested a vendor-neutral EPI sequence for imaging HP 13C agents. We have made all of our sequence creation and image reconstruction code freely available online for other investigators to use.

Abbreviated Dialectical Behavior Therapy Virtual Skills Group for Caregivers of Adolescents: An Exploratory Study of Service User and Clinical Outcomes.

Prior work emphasizes involving caregivers in youth mental health services. To support youth with emotion dysregulation, dialectical behavior therapy for adolescents (DBT-A) includes a multi-family skills group, wherein adolescents and caregivers learn skills together. However, limited work has examined the impact of caregiver involvement within DBT-A. The current study examines outcomes of two caregiver-only DBT-A skills groups adapted for abbreviated telehealth delivery. We report on caregivers' (N = 11, 100% mothers, 55% Hispanic) service user outcomes (e.g. self-efficacy at skill usage, group cohesion, therapeutic alliance) and clinical outcomes (i.e. their own emotion functioning, criticism, responses to their adolescent's negative emotions). Results indicate caregiver-only groups were feasible and acceptable, and suggest preliminary efficacy, including improvements in caregiver emotion functioning, distress during interactions with their adolescents, and adolescent-reported criticism. Caregivers also reported reductions in unsupportive responses with their adolescents. Overall, while we caution interpretation due to a small sample size, findings support the preliminary feasibility and efficacy of modifying caregiver participation in DBT-A to be less time-consuming and administered via telehealth.

Learning from Adolescents and Caregivers to Enhance Acceptability and Engagement Within Virtual Dialectical Behavior Therapy for Adolescents Skills Groups: A Qualitative Study.

Despite the significant increase in adolescent mental health challenges in recent years, structural barriers continue to limit access to and engagement in mental health services. As such, opportunities to learn directly from adolescents and their families on how to best structure and deliver services are paramount. The current study assumes a multi-informant approach and reports on adolescents' and caregivers' (N = 33) experiences in an adapted telehealth/hybrid Dialectical Behavior Therapy for Adolescents (DBT-A) program. Focus groups were conducted across two cohorts of families who participated in DBT-A skills groups, to collect family-centered data on the acceptability of program modifications, engagement in the adapted telehealth/hybrid DBT-A, and recommendations for improvement. Participants were predominately Latine White and were from a broad range of socioeconomic backgrounds. Additionally, 45.5% of the adolescents identified as LGBTQ + . Focus group findings emphasized how the telehealth platform was both convenient and disengaging, and how in-person sessions offered improved group connection and content engagement. Participants underscored the importance of balancing multi-family group sessions with adolescent- and caregiver-only group sessions in the program, and adolescents emphasized a need for the DBT-A program to better center adolescents' unique experiences and voices throughout sessions. Both adolescents and caregivers suggested modifications to synthesize the content and improve generalizability of the DBT-A skills to their real lives. Overall, these findings add to a new and evolving branch of DBT-A qualitative inquiry, as well as the growing body of work that recommends incorporating the voices of people with lived experiences into the development and modification of psychological services.

A Virtual Photovoice Study of Older African Americans Perceptions of Neurovascular Clinical Trials.

BACKGROUND: Alzheimer disease (AD) poses a major public health crisis, especially among African Americans (AAs) who are up to 3 times more likely to develop AD compared with non-Hispanic Whites. Moreover, cardiovascular risk factors represent a precursor to cognitive decline, which contributes to racial/ethnic disparities seen within AD. Despite these disparities, AAs are underrepresented in neurovascular research. The purpose of this qualitative virtual photovoice project is to explore how older Midwestern AAs perceive neurovascular clinical trials. METHODS: Five photovoice sessions were held virtually over a 3-month period. Participants took photos each week that captured the salient features of their environment that described their perceptions and experiences related to neurovascular clinical trials. Structured discussion using the SHOWED method was used to generate new understandings about the perspectives and experiences in neurovascular clinical trials. Data was analyzed using strategies in participatory visual research. RESULTS: A total of 10 AAs aged 55 years and older participated and a total of 6 themes emerged from the photovoice group discussions. CONCLUSION: Findings from this study inform the development of culturally appropriate research protocols and effective recruitment strategies to enhance participation among older AAs in neurovascular clinical trials.

Measuring clinician stuck points about trauma-focused cognitive behavior therapy: The TF-CBT Stuck Points Questionnaire.

Although evidence-based treatments (EBTs) for youth trauma have been developed, trauma-informed EBTs are rarely used in community settings. Clinician concerns about evidence-based trauma treatment may be a barrier to adoption and delivery. However, few instruments to assess clinician beliefs about specific EBTs, such as trauma-focused cognitive behavior therapy (TF-CBT) are available. This study evaluated an instrument of clinician concerns about TF-CBT, the TF-CBT Therapist Stuck Points questionnaire, in a sample of community mental health clinicians training in a year-long TF-CBT community-based learning collaborative. The 26 items in the instruments, which aim to assess clinician views on child trauma treatment and TF-CBT, indicate preliminary psychometric support (i.e., item-total correlations, internal consistency, negative correlations with measures of attitudes towards evidence-based practice). Scores on the TF-CBT Therapist Stuck Points questionnaire revealed that, on average, clinicians expressed concerns about having children talk about their trauma in session, the effectiveness of certain TF-CBT components, and whether to involve caregivers in treatment. Clinician doubts could be targeted during a TF-CBT implementation effort and clinical supervision to facilitate treatment delivery. Implications for assessing TF-CBT specific beliefs during implementation are discussed.

Effectiveness of non-pharmaceutical interventions on cognitive function among non-demented African American and Latino older adults in the USA: a scoping review.

OBJECTIVE: African Americans and Latinos/Hispanics have a higher prevalence of dementia compared to non-Latino Whites. This scoping review aims to synthesize non-pharmaceutical interventions to delay or slow age-related cognitive decline among cognitively healthy African American and Latino older adults. DESIGN: A literature search for articles published between January 2000 and May 2019 was performed using the databases PubMed, CINAHL, PsycINFO and Web of Science. Relevant cited references and grey literature were also reviewed. Four independent reviewers evaluated 1,181 abstracts, and full-article screening was subsequently performed for 145 articles. The scoping review consisted of eight studies, which were evaluated according to the peer-reviewed original manuscript, non-pharmaceutical intervention, cognitive function as an outcome, separate reporting of results for African American and Latinos, minimum age of 40, and conducted in the US. A total of 8 studies were considered eligible and were analyzed in the present scoping review. RESULTS: Eight studies were identified. Four studies focused on African Americans and four focused on Latinos. Through the analysis, results indicated cognitive training-focused interventions were effective in improving memory, executive function, reasoning, visuospatial, psychological function, and speed among African Americans. Exercise interventions were effective in improving cognition among Latinos. CONCLUSION: This scoping review identified effective non-pharmaceutical interventions among African American and Latinos. Effective interventions focused on cognitive training alone for African Americans and exercise combined with group educational sessions for Latinos. Future research should explore developing culturally appropriate non-pharmaceutical interventions to reduce disparities and to enhance cognition among older African American and Latinos.

Primary Outcomes for Adults Receiving the Unified Protocol after Hurricane Harvey in an Integrated Healthcare Setting.

The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) has demonstrated efficacy for treating anxiety and depression. However, there are limited effectiveness data when conducted in real-world settings with diverse populations, including those with trauma. We evaluated treatment outcomes in a naturalistic, community setting among 279 adults who received UP following Hurricane Harvey. We examined change in overall clinical severity, depression and anxiety symptoms, functional impairment, and baseline outcome predictors (i.e., demographic characteristics, impact from Hurricane Harvey, co-occurrence of depression and anxiety symptoms). Global clinical severity, depression and anxiety symptoms, and functional impairment decreased by end-of-treatment. Participants experienced global symptom improvement to a lesser degree than demonstrated in efficacy trials. Participants who experienced greater storm impact reported larger reductions in anxiety symptoms than those less impacted by Harvey. Further studies evaluating the effectiveness of the UP post-disaster and with diverse samples are needed.

Sodium phosphate is superior to polyethylene glycol in constipated patients undergoing colonoscopy: a systematic review and meta-analysis.

BACKGROUND: Constipation is an important and highly prevalent predictor of inadequate bowel preparation during colonoscopy. In North America, between 2 and 28% of the general population suffer from constipation. Despite the high prevalence of constipation, to our knowledge, no meta-analysis on the optimal bowel preparation for constipated patients has been performed. We aimed to systematically review the literature to determine the ideal bowel preparation regiment for patients with chronic constipation. METHODS: A comprehensive search of electronic databases (MEDLINE, EMBASE, SCOPUS, and Web of Science) was performed. We included studies that assessed the quality of bowel preparation in constipated patients receiving different agents prior to colonoscopy. The primary outcome was colon cleanliness. Secondary outcomes included tolerability of the bowel preparation and serious adverse events. RESULTS: Preliminary database search yielded 1581 articles after duplicates were removed. After screening of the titles and abstracts using the exclusion criteria, 358 full-text articles were retained. Full-text articles were reviewed and eight studies meeting the inclusion criteria were included for qualitative synthesis. Three randomized controlled trials identified a total of 1636 constipated patients, of whom 225 were eligible for meta-analysis. Of those, 107 (47.6%) received NaP and 118 (52.4%) received PEG. Patients receiving NaP before colonoscopy had a higher chance of a successful bowel preparation than patients receiving PEG (OR 1.87, CI 1.06 to 3.32, P = 0.003). In the studies comparing PEG to NaP, two found that NaP resulted in greater tolerability of the bowel preparation and one study found that PEG resulted in superior tolerability. CONCLUSIONS: In chronically constipated patients undergoing colonoscopy, the use of NaP may result in superior colonic cleanliness when compared to PEG, however, quality of evidence was low. Further high-quality studies are required to delineate the optimal bowel preparation in patients with constipation.

Challenges and opportunities for conducting a vaccine trial during the COVID-19 pandemic in the United Kingdom.

The COVID-19 pandemic has resulted in unprecedented challenges for healthcare systems worldwide. It has also stimulated research in a wide range of areas including rapid diagnostics, novel therapeutics, use of technology to track patients and vaccine development. Here, we describe our experience of rapidly setting up and delivering a novel COVID-19 vaccine trial, using clinical and research staff and facilities in three National Health Service Trusts in Cambridgeshire, United Kingdom. We encountered and overcame a number of challenges including differences in organisational structures, research facilities available, staff experience and skills, information technology and communications infrastructure, and research training and assessment procedures. We overcame these by setting up a project team that included key members from all three organisations that met at least daily by teleconference. This group together worked to identify the best practices and procedures and to harmonise and cascade these to the wider trial team. This enabled us to set up the trial within 25 days and to recruit and vaccinate the participants within a further 23 days. The lessons learned from our experiences could be used to inform the conduct of clinical trials during a future infectious disease pandemic or public health emergency.

Risk of mild cognitive impairment among older adults in the United States by ethnoracial group.

OBJECTIVES: To compare the risk of mild cognitive impairment (MCI) among a wide range of ethnoracial groups in the US. DESIGN: Non-probabilistic longitudinal clinical research. SETTING: Participants enrolling into the National Alzheimer's Coordinating Center Unified Data Set recruited via multiple approaches including clinician referral, self-referral by patients or family members, or active recruitment through community organizations. PARTICIPANTS: Cognitively normal individuals 55 and older at the initial visit, who reported race and ethnicity information, with at least two visits between September 2005 and November 2018. MEASUREMENTS: Ethnoracial information was self-reported and grouped into non-Latino Whites, Asian Americans, Native Americans, African Americans (AAs), and individuals simultaneously identifying as AAs and another minority race (AA+), as well as Latinos of Caribbean, Mexican, and Central/South American origin. MCI was evaluated clinically following standard criteria. Four competing risk analysis models were used to calculate MCI risk adjusting for risk of death, including an unadjusted model, and models adjusting for non-modifiable and modifiable risk factors. RESULTS: After controlling for sex and age at initial visit, subhazard ratios of MCI were statistically higher than non-Latino Whites among Native Americans (1.73), Caribbean Latinos (1.80), and Central/South American Latinos (1.55). Subhazard ratios were higher among AA+ compared to non-Latino Whites only in the model controlling for all risk factors (1.40). CONCLUSION: Compared to non-Latino Whites, MCI risk was higher among Caribbean and South/Central American Latinos as well as Native Americans and AA+. The factors explaining the differential MCI risk among ethnoracial groups are not clear and warrant future research.

Risk of Lower Birth Weight and Shorter Gestation in Oocyte Donation Pregnancies Compared With Other Assisted Reproductive Technology Methods: Systematic Review.

OBJECTIVE: Oocyte donation (OD) is associated with an increased risk of pregnancy-induced hypertension, but the evidence of an association between OD and infant outcomes, including birth weight and gestational age, is conflicting. This study sought to determine the associations between oocyte donation and birth weight or gestational age compared with other forms of autologous oocyte assisted reproductive technology (ART). METHODS: Medline, Embase, and the CENTRAL Trials Registry of the Cochrane Collaboration were searched using a comprehensive search strategy. Studies of women over 24 weeks gestation compared infant outcomes among OD pregnancies versus other ART. Study quality was assessed, and a meta-analysis of mean birth weight and gestational age was conducted using a random effects model. RESULTS: Nineteen studies were included. Four studies showed a significant association between OD and lower birth weights, and five studies found significant differences in gestational age between OD and autologous oocyte ART. The pooled difference in birth weight means between OD and autologous ART was -42 (-88, 4) . The pooled difference in gestational age was -0.4 weeks (-0.8, 0.0 weeks). CONCLUSION: A high degree of interstudy heterogeneity exists, and the association between OD and infant outcomes remains unclear.

Simethicone decreases bloating and improves bowel preparation effectiveness: a systematic review and meta-analysis.

BACKGROUND: Simethicone is an adjunct frequently used during bowel preparation before colonoscopy and currently there is no consensus on whether it should be recommended in standard bowel preparation. We performed a systematic review and meta-analysis to determine the effect simethicone has on bowel cleanliness, adenoma detection rate (ADR), and tolerability. METHODS: We searched the literature for studies that compared colon cleansing of patients that received standard bowel preparation alone and in combination with simethicone prior to colonoscopy. The primary outcomes were colon cleanliness, ADR, and tolerability. RESULTS: Sixteen randomized controlled trials with 5630 patients were included in meta-analysis. Overall, polyethylene glycol (PEG) with simethicone improves colon cleansing compared with PEG alone (odds ratio [OR] 1.48, CI 1.11 to 1.97, P = 0.008). This improvement was seen for single dosing (OR 1.83, CI 1.20 to 2.79, P = 0.005) but not for split dosing (OR 1.32, CI 0.72 to 2.43, P = 0.38). Overall, simethicone had no effect on ADR (OR 1.22, CI 0.81 to 1.83, P = 0.33), but in patients receiving single dosing, simethicone significantly increased ADR (OR 1.96, CI 1.22 to 3.16, P = 0.005). The rates of nausea (OR 0.96, CI 0.75 to 1.24, P = 0.75), vomiting (OR 1.00, CI 0.69 to 1.44, P = 0.99), and abdominal pain (OR 0.69, CI 0.40 to 1.18, P = 0.17) were not significantly different between PEG and PEG + simethicone cohorts. For abdominal bloating, the PEG cohort had greater odds of experiencing bloating than the PEG + simethicone cohort (OR 2.33, CI 1.70 to 3.20, P < 0.00001). CONCLUSIONS: Simethicone improves colon cleanliness and ADR; however, this improvement is not seen in patients receiving split-dose PEG. Furthermore, simethicone decreases abdominal bloating but has no effect on nausea, vomiting, and abdominal pain. Simethicone may be a useful bowel preparation adjunct in patients unable to receive split-dose PEG.

Preaching to the Choir? Predictors of Engagement in a Community-Based Learning Collaborative.

This study examined predictors of engagement among 283 professionals from 34 agencies participating in three community-based learning collaboratives (CBLCs) on trauma-focused cognitive-behavioral therapy (TF-CBT). Only 50.2% of participants completed the CBLC, primarily due to not attending consultation calls or completing training cases. While higher engagement was associated with being trauma-informed and using more of the TF-CBT components prior to the CBLC, most predictors were not significant, perhaps due to ceiling effects. Positive attitudes and high organizational support were not sufficient to ensure engagement. Future research using longitudinal measurement of a wider range of predictors is needed.

Shame and Defectiveness Beliefs in Treatment Seeking Patients With Body Dysmorphic Disorder.

Shame is a distressing emotion experienced when individuals judge themselves in a broadly negative and critical manner. Clinical descriptions of body dysmorphic disorder (BDD) emphasize the centrality of shame, yet research on shame in BDD remains scarce. This study is the largest investigation of shame in clinically diagnosed individuals with BDD, and it is the first to examine whether shame changes with treatment. Eighty-three adults with BDD were treated with 14 weeks of open-label escitalopram. Shame was measured using the Young Schema Questionnaire-Short Form. Shame was significantly higher in individuals with BDD than in previously reported healthy control and psychiatric outpatient samples. Shame was significantly, moderately correlated with greater suicidal thoughts and hopelessness and marginally significantly correlated with greater BDD severity. Shame decreased significantly with treatment. Reductions in shame with escitalopram were significantly associated with reductions in suicidal thoughts and hopelessness, even when accounting for reductions in BDD and depression severity.

The Relationship between Traumatic Life Events and Hoarding Symptoms: A Multi-Method Approach.

Hoarding Disorder is characterized by difficulties with discarding and frequently excessively acquiring possessions, resulting in substantial clutter. Previous research has implicated trauma in the development of hoarding, but no study to date has examined the relationship between trauma and hoarding using hypothetical hoarding paradigms. This study investigated the association between traumatic events and both self-report and hypothetical indices of hoarding symptoms. We predicted that frequency of trauma would be associated with greater hoarding symptoms (across self-report and hypothetical indices). Undergraduate students (N = 80) completed self-report measures of hoarding symptoms and trauma, and hypothetical measures of acquiring and saving tendencies. As expected, more frequent trauma, and physical/sexual trauma in particular, was associated with greater acquiring tendencies. However, frequency of trauma was not significantly correlated with saving tendencies or self-reported hoarding symptoms. Future research should replicate these findings using longitudinal designs to confirm whether trauma actually serves as a risk factor for hoarding. Replication in a clinical sample is needed to better understand the implications of these results for intervention.

Risk environments facing potential users of a supervised injection site in Ottawa, Canada.

BACKGROUND: Supervised injection sites (SISs) have been effective in reducing health risks among people who inject drugs (PWID), including those who face issues of homelessness, mental health illness, interactions with local policing practices, and HIV infection. We investigate the risk behaviours and risk environments currently faced by potential users of an SIS in Ottawa to establish the need for such a service and to contribute to the design of an SIS that can address current health risks and reduce harm. METHODS: The PROUD cohort is a community-based participatory research (CBPR) project that examines the HIV risk environment among people who use drugs in Ottawa. From March to October 2013, 593 people who reported using injection drugs or smoking crack cocaine were enrolled through street-based recruitment in the ByWard Market neighbourhood, an area of the city with a high concentration of public drug use and homelessness. Participants completed a demographic, behavioural, and risk environment questionnaire and were offered HIV point-of-care testing. We undertook descriptive and univariate analyses to estimate potential use of an SIS by PWID in Ottawa and to explore risk behaviours and features of the risk environment faced by potential users of the service. RESULTS: Of those participants who reported injecting drugs in the previous 12 months (n = 270), 75.2 % (203) reported a willingness to use an SIS in Ottawa. Among potential SIS users, 24.6 % had recently injected with a used needle, 19.0 % had trouble accessing new needles, 60.6 % were unstably housed, 49.8 % had been redzoned by the police, and 12.8 % were HIV positive. Participants willing to use an SIS more frequently injected in public (OR = 1.98, 95 % CI = 1.06-3.70), required assistance to inject (OR = 1.84, 95 % CI = 1.00-3.38), were hepatitis C positive (OR = 2.13, 95 % CI = 1.16-3.91), had overdosed in the previous year (OR = 2.00, 95 % CI = 1.02-3.92), and identified as LGBTQ (OR = 5.61, 95 % CI = 1.30-24.19). CONCLUSION: An SIS in Ottawa would be well-positioned to reach its target group of highly marginalized PWID and reduce drug-related harms. The application of CBPR methods to a large-scale quantitative survey supported the mobilization of communities of PWID to identify and advocate for their own service needs, creating an enabling environment for harm reduction action.

Establishing a community-based participatory research partnership among people who use drugs in Ottawa: the PROUD cohort study.

BACKGROUND: Grounded in a community-based participatory research (CBPR) framework, the PROUD (Participatory Research in Ottawa: Understanding Drugs) Study aims to better understand HIV risk and prevalence among people who use drugs in Ottawa, Ontario. The purpose of this paper is to describe the establishment of the PROUD research partnership. METHODS: PROUD relies on peers' expertise stemming from their lived experience with drug use to guide all aspects of this CBPR project. A Community Advisory Committee (CAC), comprised of eight people with lived experience, three allies and three ex-officio members, has been meeting since May 2012 to oversee all aspects of the project. Eleven medical students from the University of Ottawa were recruited to work alongside the committee. Training was provided on CBPR; HIV and harm reduction; and administering HIV point-of-care (POC) tests so that the CAC can play a key role in research design, data collection, analysis, and knowledge translation activities. RESULTS: From March-December 2013, the study enrolled 858 participants who use drugs (defined as anyone who has injected or smoked drugs other than marijuana in the last 12 months) into a prospective cohort study. Participants completed a one-time questionnaire administered by a trained peer or medical student, who then administered an HIV POC test. Recruitment, interviews and testing occurred in both the fixed research site and various community settings across Ottawa. With consent, prospective follow-up will occur through linkages to health care records available through the Institute for Clinical and Evaluation Sciences. CONCLUSION: The PROUD Study meaningfully engaged the communities of people who use drugs in Ottawa through the formation of the CAC, the training of peers as community-based researchers, and integrated KTE throughout the research project. This project successfully supported skill development across the team and empowered people with drug use experience to take on leadership roles, ensuring that this research process will promote change at the local level. The CBPR methods developed in this study provide important insights for future research projects with people who use drugs in other settings.

A retrospective analysis of serious adverse events and deaths in U.S.-based lifestyle clinical trials for cognitive health.

Objective: This retrospective analysis examined serious adverse events (SAEs) and deaths in U.S. lifestyle clinical trials aimed at enhancing cognitive health in older adults. Methods: Data was gathered from trials completed between January 1, 2000, and July 19, 2023, via ClinicalTrials.gov's API. Results: Among these trials, 76% did not report results. The remaining studies fell into four intervention categories: Cognitive/Behavioral, Exercise/Movement, Diet/Supplement, and Multi-modal. When considering all trial types collectively, the findings suggest that lifestyle clinical trials are generally safe. There was no significant increase in the relative risk of experiencing an SAE in the intervention group compared to the control group. However, in terms of relative risk of death, an increase of 28% was observed in the intervention compared to the control, which was statistically significant (X2 (1, N = 36), p < 0.00688). Nevertheless, this increase did not surpass age-adjusted U.S. mortality rates. Assessing the data by intervention type, Diet/Supplement, and Multi-modal trials displayed an elevated relative risk of SAEs in the intervention. Diet/Supplement trials had a 16% increase (X2 (1, N = 2), p < 0.0263), and Multi-modal trials had a 365% increase (X2 (1, N = 5), p < 0.000213). Diet/Supplement trials also showed a 67% increased risk of death (X2 (1, N = 2), p < 0.000197). Conclusions: These findings should be cautiously considered due to the low rate of reporting, but underscore the significance of reporting clinical trial results, enhancing transparency, and facilitating more accurate safety assessments in cognitive aging and lifestyle interventions for older adults.

Detection of early-stage NASH using non-invasive hyperpolarized 13C metabolic imaging.

Non-alcoholic steatohepatitis (NASH) is characterized from its early stages by a profound remodeling of the liver microenvironment, encompassing changes in the composition and activities of multiple cell types and associated gene expression patterns. Hyperpolarized (HP) 13C MRI provides a unique view of the metabolic microenvironment, with potential relevance for early diagnosis of liver disease. Previous studies have detected changes in HP 13C pyruvate to lactate conversion, catalyzed by lactate dehydrogenase (LDH), with experimental liver injury. HP ∝ -ketobutyrate ( ∝ KB) is a close molecular analog of pyruvate with modified specificity for LDH isoforms, specifically attenuated activity with their LDHA-expressed subunits that dominate liver parenchyma. Building on recent results with pyruvate, we investigated HP ∝ KB in methionine-choline deficient (MCD) diet as a model of early-stage NASH. Similarity of results between this new agent and pyruvate (~ 50% drop in cytoplasmic reducing capacity), interpreted together with gene expression data from the model, suggests that changes are mediated through broad effects on intermediary metabolism. Plausible mechanisms are depletion of the lactate pool by upregulation of gluconeogenesis (GNG) and pentose phosphate pathway (PPP) flux, and a possible shift toward increased lactate oxidation. These changes may reflect high levels of oxidative stress and/or shifting macrophage populations in NASH.