Gestational buprenorphine-naloxone exposure and fetal neurobehavior.

BACKGROUND: Buprenorphine-naloxone treatment may confer substantial benefits for the treatment of opioid use disorder (OUD) during pregnancy including lower risk for overdose/death, less diversion potential and reduced use of other substances. Treatment may also result in less severe Neonatal Abstinence Syndrome (NAS), but little is known about the effects of this medication on fetal neurodevelopment. METHODS: The purpose of the current study is to evaluate neurobehaviors among fetuses exposed to buprenorphine-naloxone at four time points over the second and third trimesters of gestation in pregnant women with OUD on buprenorphine-naloxone therapy. Sixty minutes of continuous fetal monitoring via fetal actocardiograph with a single wide array abdominal transducer took place at times of peak and trough buprenorphine-naloxone levels in 24 pregnant women. Data collection, which included measures of fetal heart rate and motor activity, was conducted between 24 and 36 weeks gestation, with the majority (84.6%) monitored at two or more gestational ages. Medication dose and other substance use was monitored throughout the study and infant NAS severity was assessed. RESULTS: Fetal heart rate (FHR), FHR variability, accelerations in FHR, and motor activity were suppressed when buprenorphine-naloxone levels were at pharmacologic peak as compared to trough concentrations at 36 weeks, but not earlier in gestation. Maternal medication dose was unrelated to infant NAS severity. CONCLUSIONS: Conclusions: There were evident subclinical fetal neurophysiological responses at times of peak maternal buprenorphine/naloxone levels in later gestation, similar to those previously described for buprenorphine only. Further studies evaluating the effects of these changes in fetal neurobehaviors on the longer-term infant development are needed.

The Relationship Between First Presenting Neuropsychiatric Symptoms in Older Adults and Autopsy-Confirmed Memory Disorders.

OBJECTIVES: Although dementia is typically considered a disease of cognitive decline, almost all patients present with neuropsychiatric symptoms (NPS) at some stage of their disease. Few studies have assessed the timing of NPS onset in relation to pathological diagnoses of neurodegenerative diseases. We sought to examine the association between the first presenting clinically significant NPS in aging individuals and neuropathological diagnoses of memory disorders. DESIGN: This retrospective longitudinal cohort study utilized the National Alzheimer's Coordinating Center (NACC) dataset, which includes participant data from 37 Alzheimer's Disease Research Centers collected between 2005 and 2022. PARTICIPANTS: Participants (N = 5,416) aged 45 years or older with Clinical Dementia Rating-Global ratings of less than or equal to 1 were included in this analysis. A total of 4,033 (74.5%) participants presented with at least one NPS at any NACC visit. MEASUREMENTS: To measure first NPS, the NACCBEHF variable was used, a clinician-rated variable defined as "the predominant symptom that was first recognized as a decline in the subject's behavior." Neuropathologic variables included assessments of Alzheimer's Disease, Frontotemporal Dementia, Lewy Body Dementia, Cerebral Amyloid Angiopathy, Hippocampal Sclerosis, and Cerebrovascular Disease. RESULTS: Presentation with any clinically significant first NPS was associated with several neuropathological diagnoses including Alzheimer's Disease, Frontotemporal Lobar Dementia with TDP-43 pathology, and Lewy Body Dementia. While specific first NPS were associated with Frontotemporal Dementia neuropathology (personality change and disinhibition) and Lewy Body Dementia neuropathology (psychosis and REM behavior disturbance), Alzheimer's Disease neuropathology was associated with the majority of NPS. CONCLUSIONS: Since neuropsychiatric symptoms are frequently the first presenting symptom of dementia, their associations with well-defined neuropathological diagnoses may help clinicians predict the subtype of future dementias.

Identification of Fatigue Subtypes and Their Correlates in Prevalent Heart Failure: A Secondary Analysis of the Atherosclerosis Risk in Communities Study.

BACKGROUND: Among patients with heart failure (HF), fatigue is common and linked to quality of life and functional status. Fatigue is hypothesized to manifest as multiple types, with general and exertional components. Unique subtypes of fatigue in HF may require differential assessment and treatment to improve outcomes. We conducted this study to identify fatigue subtypes in persons with prevalent HF in the ARIC study (Atherosclerosis Risk in Communities) and describe the distribution of characteristics across subtypes. METHODS: We performed a cross-sectional analysis of 1065 participants with prevalent HF at ARIC visit 5 (2011-2013). We measured exertional fatigue using the Modified Medical Research Council Breathlessness scale and general fatigue using the Patient Reported Outcomes Measurement Information System fatigue scale. We used latent class analysis to identify subtypes of fatigue. Number of classes was determined using model fit statistics, and classes were interpreted and assigned fatigue severity rating based on the conditional probability of endorsing survey items given class. We compared characteristics across classes using multinomial regression. RESULTS: Overall, participants were 54% female and 38% Black with a mean age of 77. We identified 4 latent classes (fatigue subtypes): (1) high general/high exertional fatigue (18%), (2) high general/low exertional fatigue (27%), (3) moderate general/moderate exertional fatigue (20%), and (4) low/no general and exertional fatigue (35%). Female sex, Black race, lower education level, higher body mass index, increased depressive symptoms, and higher prevalence of diabetes were associated with higher levels of general and exertional fatigue. CONCLUSIONS: We identified unique subtypes of fatigue in patients with HF who have not been previously described. Within subtype, general and exertional fatigue were mostly concordant in severity, and exertional fatigue only occurred in conjunction with general fatigue, not alone. Further understanding these fatigue types and their relationships to outcomes may enhance our understanding of the symptom experience and inform prognostication and secondary prevention efforts for persons with HF.

Randomized controlled trial of zolpidem as a pharmacotherapy for cannabis use disorder.

BACKGROUND: Sleep disturbance is commonly reported among individuals meeting criteria for cannabis use disorder (CUD), and people who use cannabis frequently report sleep disturbance as a contributor to failed quit attempts. The purpose of this study was to measure sleep in individuals enrolled in treatment for CUD, and to determine whether use of hypnotic medication during treatment increased abstinence rates. METHOD: The study enrolled 127 adults seeking treatment for CUD in a 12-week clinical trial and randomized to receive extended-release zolpidem (zolpidem-XR) or placebo. All participants received computerized behavioral therapy and abstinence-based contingency management. The study conducted in-home ambulatory polysomnography (PSG) assessments at baseline and during treatment to objectively measure sleep. Self-report measures of recent sleep, Insomnia Severity Index (ISI), and drug use (Timeline Follow-Back) were collected at each study visit, and the study confirmed self-reported abstinence via quantitative urine drug testing. RESULT: Participants randomized to placebo, but not zolpidem-XR exhibited significant sleep disturbance during week 1 of treatment. Sleep disturbance emerged in the zolpidem-XR group after study medication was stopped at the end of treatment. Though participants assigned to the zolpidem-XR condition had qualitatively greater rates of abstinence compared with placebo (27 % versus 15 % negative at end of treatment), the difference was not statistically significant. Treatment retention was poor (about 50 % drop out in both groups) and medication adherence was a challenge without the use of contingent incentives. CONCLUSION: Results from this randomized controlled trial suggest that zolpidem-XR can attenuate abstinence-induced sleep disturbance early in treatment for CUD, but that sleep problems are likely to emerge after the medication is stopped. Further research should identify alternative pharmacotherapies and behavioral treatments for CUD and elucidate the role of sleep disturbance in the development and maintenance of CUD.

Long-Term Effects of Incentives for HIV Viral Suppression: A Randomized Clinical Trial.

Achieving viral suppression in people living with HIV improves their quality of life and can help end the HIV/AIDS epidemic. However, few interventions have successfully promoted HIV viral suppression. The purpose of this study was to evaluate the long-term effectiveness of financial incentives for viral suppression in people living with HIV. People living with a detectable HIV viral load (≥ 200 copies/mL) were randomly assigned to Usual Care (n = 50) or Incentive (n = 52) groups. Incentive participants earned up to $10 per day for providing blood samples with an undetectable or reduced viral load. During the 2-year intervention period, the percentage of blood samples with a suppressed viral load was significantly higher among Incentive participants (70%) than Usual Care participants (43%) (OR = 7.1, 95% CI 2.7 to 18.8, p < .001). This effect did not maintain after incentives were discontinued. These findings suggest that frequent delivery of large-magnitude financial incentives for viral suppression can produce large and long-lasting improvements in viral load in people living with HIV. ClinicalTrials.gov Identifier: NCT02363387.

Comparative assessment of Alzheimer's disease-related biomarkers in plasma and neuron-derived extracellular vesicles: a nested case-control study.

Introduction: Alzheimer's disease (AD) is currently defined according to biomarkers reflecting the core underlying neuropathological processes: Aß deposition, Tau, and neurodegeneration (ATN). The soluble phase of plasma and plasma neuron-derived extracellular vesicles (NDEVs) are increasingly being investigated as sources of biomarkers. The aim of this study was to examine the comparative biomarker potential of these two biofluids, as well as the association between respective biomarkers. Methods: We retrospectively identified three distinct diagnostic groups of 44 individuals who provided samples at baseline and at a mean of 3.1 years later; 14 were cognitively unimpaired at baseline and remained so (NRM-NRM), 13 had amnestic MCI that progressed to AD dementia (MCI-DEM) and 17 had AD dementia at both timepoints (DEM-DEM). Plasma NDEVs were isolated by immunoaffinity capture targeting the neuronal markers L1CAM, GAP43, and NLGN3. In both plasma and NDEVs, we assessed ATN biomarkers (Aß42, Aß40, total Tau, P181-Tau) alongside several other exploratory markers. Results: The Aß42/Aß40 ratio in plasma and NDEVs was lower in MCI-DEM than NRM-NRM at baseline and its levels in NDEVs decreased over time in all three groups. Similarly, plasma and NDEV-associated Aß42 was lower in MCI-DEM compared to NRM-NRM at baseline and its levels in plasma decreased over time in DEM-DEM. For NDEV-associated proBDNF, compared to NRM-NRM, its levels were lower in MCI-DEM and DEM-DEM at baseline, and they decreased over time in the latter group. No group differences were found for other exploratory markers. NDEV-associated Aß42/Aß40 ratio and proBDNF achieved the highest areas under the curve (AUCs) for discriminating between diagnostic groups, while proBDNF was positively associated with Mini-Mental State Examination (MMSE) score. No associations were found between the two biofluids for any assessed marker. Discussion: The soluble phase of plasma and plasma NDEVs demonstrate distinct biomarker profiles both at a single time point and longitudinally. The lack of association between plasma and NDEV measures indicates that the two types of biofluids demonstrate distinct biomarker signatures that may be attributable to being derived through different biological processes. NDEV-associated proBDNF may be a useful biomarker for AD diagnosis and monitoring.

Serotonin Degeneration and Amyloid-ß Deposition in Mild Cognitive Impairment: Relationship to Cognitive Deficits.

BACKGROUND: Neuropathological and neuroimaging studies have demonstrated degeneration of the serotonin system in Alzheimer's disease (AD). Neuroimaging studies have extended these observations to the preclinical stages of AD, mild cognitive impairment (MCI). Serotonin degeneration has been observed also in transgenic amyloid mouse models, prior to widespread cortical distribution of amyloid-ß (Aß). OBJECTIVE: The present study evaluated the regional distribution of the serotonin transporter (5-HTT) and of Aß in individuals with MCI and healthy older controls, as well as the contribution of 5-HTT and Aß to cognitive deficits. METHODS: Forty-nine MCI participants and 45 healthy older controls underwent positron emission tomography (PET) imaging of 5-HTT and Aß, structural magnetic resonance imaging and neuropsychological assessments. RESULTS: Lower cortical, striatal, and limbic 5-HTT and higher cortical Aß was observed in MCIs relative to healthy controls. Lower 5-HTT, mainly in limbic regions, was correlated with greater deficits in auditory-verbal and visual-spatial memory and semantic, not phonemic fluency. Higher cortical A ß was associated with greater deficits in auditory-verbal and visual-spatial memory and in semantic, not phonemic fluency. When modeling the association between cognition, gray matter volumes and Aß, inclusion of 5-HTT in limbic and in select cortical regions significantly improved model fit for auditory-verbal and visual-spatial memory and semantic, but not phonemic fluency. CONCLUSIONS: These results support the role of serotonin degeneration in the memory and semantic fluency deficits observed in MCI.

Weight Change and Neuropsychiatric Symptoms in Alzheimer's Disease and Frontotemporal Dementia: Associations with Cognitive Decline.

Weight changes, neuropsychiatric symptoms (NPS), and cognitive decline often coincide in Alzheimer's disease (AD) and frontotemporal dementia (FTD); however, the direction of their relationship remains unclear. This study aims to clarify the connection between weight changes, NPS, and cognition in AD and FTD. We found that cognitive decline was associated with decreased body mass index (BMI) in AD, while BMI gain was associated with increased conversion to FTD. Elevated NPS were associated with decreased BMI in AD and increased BMI in FTD. Identifying early changes in NPS and BMI may facilitate the detection of cognitive decline, providing an opportunity for early intervention.

Abstinence-contingent wage supplements for adults experiencing homelessness and alcohol use disorder: A randomized clinical trial.

This study evaluated the effectiveness of abstinence-contingent wage supplements in promoting alcohol abstinence and employment in adults experiencing homelessness and alcohol use disorder. A randomized clinical trial was conducted from 2019 to 2022. After a 1-month Induction period, 119 participants were randomly assigned to a Usual Care Control group (n = 57) or an Abstinence-Contingent Wage Supplement group (n = 62). Usual Care participants were offered counseling and referrals to employment and treatment programs. Abstinence-Contingent Wage Supplement participants could earn stipends for working with an employment specialist and wage supplements for working in a community job but had to maintain abstinence from alcohol as determined by transdermal alcohol concentration monitoring devices to maximize pay. Abstinence-Contingent Wage Supplement participants reported significantly higher rates of alcohol abstinence than Usual Care participants during the 6-month intervention (82.8% vs. 60.2% of months, OR = 3.4, 95% CI 1.8 to 6.3, p < .001). Abstinence-Contingent Wage Supplement participants were also significantly more likely to obtain employment (51.3% vs. 31.6% of months, OR = 2.6, 95% CI 1.5 to 4.4, p < .001) and live out of poverty (38.2% vs. 16.7% of months, OR = 3.7, 95% CI 2.0 to 7.1, p < .001) than Usual Care participants. These findings suggest that Abstinence-Contingent Wage Supplements can promote alcohol abstinence and employment in adults experiencing homelessness and alcohol use disorder. ClinicalTrials.gov Identifier: NCT03519009.

The associations between unmet needs with protective factors, risk factors and outcomes among care partners of community-dwelling persons living with dementia.

OBJECTIVES: Describe the prevalence and types of unmet needs among community-dwelling dementia care partners (CPs) and determine associations between unmet needs with protective factors, risk factors and outcomes. METHOD: A cross-sectional analysis of 638 racially and cognitively diverse community-dwelling persons living with dementia (PLWD) and their CPs participating in a comprehensive in-home assessment of dementia-related needs. Unmet CP needs (19 items, 6 domains) were rated by a clinician using the Johns Hopkins Dementia Care Needs Assessment (JHDCNA). Multivariate linear regression models were used to examine associations between total percent unmet CP needs with demographic, protective and risk factors. RESULTS: Nearly all CPs had at least one unmet need (99.53%), with a mean of 5.7 (±2.6). The most common domains with ≥1 unmet need were memory disorder education, care skills and knowledge of resources (98%), legal issues/concerns (73.8%), CP mental health (44.6%) and access to informal support (42.7%). Adjusted multivariate models suggest the strongest consistent predictive factors relate to informal emotional support, CP physical health, use or difficulty getting formal services/supports (both for CPs and PLWD), and CP time spent with PLWD. Greater levels of unmet needs were associated with worse PLWD outcomes and CP outcomes, after adjusting for demographics. CONCLUSIONS: CPs have high rates of diverse, but modifiable unmet needs. Data suggest optimal approaches to dementia care should take a family-centered home-based approach that includes routine CP needs assessment, offer targeted interventions that include both traditional medical supports as well as strategies to increase and leverage informal social networks, and ones that can bridge and coordinate medical with non-medical supports. These findings can be used to inform new approaches to support CPs, improve PLWD and CP outcomes, and target groups most at risk for inequities.

'Anxious fluctuators' a subgroup of Parkinson's disease with high anxiety and problematic on-off fluctuations.

Anxiety that occurs in association with on-off dopamine medication fluctuations is a major cause of distress, dysfunction, and lower quality of life in people with Parkinson's disease (PD). However, the association between anxiety and on-off fluctuations is poorly understood and it is difficult to predict which patients will suffer from this atypical form of anxiety. To understand whether fluctuating anxiety in PD exists as part of an endophenotype that is associated with other signs or symptoms, we prospectively assessed the change in anxiety and a battery of clinical variables when transitioning from the off-dopamine medication state to the on state in 200 people with PD. We performed latent profile analysis with observed variables as latent profile indicators measuring the on-off-state difference in anxiety, depression, motor function, daily functioning, and the wearing off questionnaire 19 item scale (WOQ-19) in order to model unobserved (i.e., latent) profiles. A two-class model produced the best fit. The majority of participants, 69%, were categorized as having a 'typical on-off response' compared to a second profile constituting 31% of the sample who experienced a worsening in anxiety in the off state that was three times that of other participants. This profile referred to as "anxious fluctuators" had a Hamilton Anxiety Rating Scale change between the off and on medication state of 10.22(32.85) compared to 3.27 (7.62), higher depression scores, greater disability and was less likely to improve on select WOQ-19 items when in the on-state. Anxious fluctuators were more likely to be male and have a family history of anxiety disorder. Given the adverse impact of this profile we believe it may be important to distinguish patients with a typical on-off response from those with this more problematic course of fluctuations.

Vestibular therapy to reduce falls in people with Alzheimer's disease: study protocol for a pilot randomized controlled trial.

BACKGROUND: Falls are highly common in patients with Alzheimer's disease (AD); around two-thirds of AD patients fall annually. Fall events are major drivers of injury, early institutionalization, and shorter survival. Balance and mobility impairment are among the most important fall risk factors in AD patients. Vestibular therapy (VT) is an effective rehabilitation intervention in improving balance and fall risk through vestibular function, but not often used in AD. We want to evaluate the feasibility of using VT to reduce falls and improve balance function in patients with AD and drive use of an existing, potentially beneficial therapy in a patient population whose high level of vestibular deficits is currently unaddressed. METHODS: The proposed pilot clinical trial will be a parallel-group randomized controlled trial. Patients with a diagnosis of mild-moderate AD, age ≥ 60, and the presence of a caregiver will be recruited from the Johns Hopkins Memory and Alzheimer's Treatment Center. Eligible patients will be offered vestibular testing. Patients with vestibular loss will be offered participation in the VT trial. One-hundred AD patients with vestibular loss will be enrolled and randomized 1:1 into the control and intervention arms of the trial. All patients will undergo baseline balance and cognitive assessment, followed by 8 weeks of active control therapy or VT, consisting of ~25-min office sessions with a vestibular therapist. Patients will be tracked for falls and undergo follow-up balance and cognitive assessment at 8 and 52 weeks (1 year) to assess the potential short-term and longer-term effects, respectively, of VT on balance and cognition. The main outcomes of this trial are falls, balance (using the Berg Balance Scale and the Timed Up and Go test), and cognition (using the clock drawing test, the Card Rotations test, the Money Road Map test, and the triangle completion task). DISCUSSION: As the population ages and the number of individuals with AD in the US grows to a projected 14 million in 2050, managing falls in AD will continue to grow as a critical public health concern; this trial assesses feasibility of a potential solution. TRIAL REGISTRATION: ClinicalTrial.Gov identifier - NCT03799991 . Registered 01 August 2019.

Graphical methods for understanding changes in states: Understanding medication use pathways.

OBJECTIVES: As epidemiological studies become longer and larger, the field needs novel graphical methods to visualize complex longitudinal data. The aim of this study was to present the Slinkyplot, a longitudinal crosstabulation, to illustrate patterns of antidepressant use in a large prospective cohort of older adults with mild cognitive impairment. METHODS: Data from the National Alzheimer's Coordinating Center are used to track switches between different states and types of antidepressant use. A Slinkyplot is populated with rows representing the state of medication use at each timepoint and columns representing the state at each subsequent visit. RESULTS: The constructed Slinkyplots display the common practice of switching on and off different antidepressants over time, with citalopram, sertraline, and bupropion most commonly used followed by switching to another SSRI or SNRI as second-line treatment. CONCLUSIONS: Slinkyplots are an innovative graphical means of visualizing complex patterns of transitions between different states over time for large longitudinal studies.

Prevalence and Correlates of Depressive Symptoms Within 6 Months After First-Time Mild Traumatic Brain Injury.

OBJECTIVE: Depressive symptoms are among the most common neuropsychiatric sequelae of mild traumatic brain injury (mTBI). Very few studies have compared correlates of depressive symptoms within the first 6 months of injury in cohorts experiencing their first TBI. The authors investigated whether the correlates of depressive symptoms (being female, older, lower education, having brain lesions, experiencing worse postconcussive symptoms, and incomplete functional recovery) that have been established in populations with moderate to severe TBI were the same for individuals with first-time mTBI within the first 6 months of recovery. METHODS: Two hundred seventeen individuals with first-time mTBI were divided into subgroups-new-onset depressive symptoms, recurrent depressive symptoms, prior depression history only, and never depressed-and compared on clinical and demographic variables and the presence of postconcussive symptoms and functional recovery at 3 and 6 months. RESULTS: New-onset depressive symptoms developed in 12% of the cohort, whereas 11% of the cohort had recurrent depressive symptoms. Both depressive symptoms groups were more likely to comprise women and persons of color and were at higher risk for clinically significant postconcussive symptoms and incomplete functional recovery for the first 6 months postinjury. CONCLUSIONS: Presence of depressive symptoms after first-time mTBI was associated with persistent postconcussive symptoms and incomplete functional recovery in the first 6 months. Adding to the existing literature, these findings identified correlates of depressive symptom development and poor outcomes after mTBI, thus providing further evidence that mTBI may produce persistent symptoms and functional limitations that warrant clinical attention.

Neuronal-Derived EV Biomarkers Track Cognitive Decline in Alzheimer's Disease.

The hallmarks of Alzheimer's disease (AD) pathology are senile plaques containing amyloid-beta (Aß) and neurofibrillary tangles containing hyperphosphorylated tau. Additional pathologies often co-exist, whereas multiple pathogenic mechanisms are involved in AD, especially synaptic degeneration, which necessitate the need for synaptic integrity-related biomarkers alongside Aß- and tau-related biomarkers. Plasma neuron-derived Extracellular Vesicles EVs (NDEVs) provide biomarkers related to Aß and tau and synaptic degeneration. Here, to further establish the latter as a "liquid biopsy" for AD, we examined their relationship with ante-mortem cognition in pathologically-confirmed AD cases. We immunoprecipitated NDEVs by targeting neuronal marker L1CAM from ante-mortem plasma samples from 61 autopsy-confirmed cases of pure AD or AD with additional pathologies and measured Aß42, p181-Tau, total Tau, synaptophysin, synaptopodin and three canonical EV markers, CD63, CD81 and CD9. Higher NDEV Aß42 levels were consistently associated with better cognitive status, memory, fluency, working memory and executive function. Higher levels of NDEV synaptic integrity-related biomarkers were associated with better performance on executive function tasks. Our findings motivate the hypothesis that releasing Aß42-laden NDEVs may be an adaptive mechanism in AD.

Abstinence-contingent wage supplements to promote drug abstinence and employment: Post-intervention outcomes.

BACKGROUND: Substance use disorder, unemployment, and poverty are interrelated problems that have not been addressed adequately by existing interventions. This study evaluated post-intervention effects of abstinence-contingent wage supplements on drug abstinence and employment. METHODS: Unemployed adults enrolled in opioid agonist treatment were randomly assigned to an abstinence-contingent wage supplement group (n = 44) or a usual care control group (n = 47). All participants could work with an employment specialist throughout a 12-month intervention period. Those in the abstinence-contingent wage supplement group earned stipends for working with the employment specialist and, after gaining employment, abstinence-contingent wage supplements for working in their community job but had to provide opiate- and cocaine-negative urine samples to maximize pay. To assess post-intervention effects of abstinence-contingent wage supplements and compare those effects to during-intervention effects, we analyzed urine samples and self-reports every 3 months during the 12-month intervention and the 12-month post-intervention period. RESULTS: During the intervention, abstinence-contingent wage supplement participants provided significantly more opiate- and cocaine-negative urine samples than usual care control participants; abstinence-contingent wage supplement participants were also significantly more likely to become employed and live out of poverty than usual care participants during intervention. During the post-intervention period, the abstinence-contingent wage supplement and usual care control groups had similar rates of drug abstinence, similar levels of employment, and similar proportions living out of poverty. CONCLUSIONS: Long-term delivery of abstinence-contingent wage supplements can promote drug abstinence and employment, but many patients relapse to drug use and cease employment when wage supplements are discontinued.

Assumptions Not Often Assessed or Satisfied in Published Mediation Analyses in Psychology and Psychiatry.

Mediation analysis aims to investigate the mechanisms of action behind the effects of interventions or treatments. Given the history and common use of mediation in mental health research, we conducted this review to understand how mediation analysis is implemented in psychology and psychiatry and whether analyses adhere to, address, or justify the key underlying assumptions of their approaches. All articles (n = 206) were from top academic psychiatry or psychology journals in the PsycInfo database and were published in English from 2013 to 2018. Information extracted from each article related to study design, covariates adjusted for in the analysis, temporal ordering of variables, and the specific method used to perform the mediation analysis. In most studies, underlying assumptions were not adhered to. Only approximately 20% of articles had full temporal ordering of exposure, mediator, and outcome. Confounding of the exposure-mediator and/or mediator-outcome relationships was controlled for in fewer than half of the studies. In almost none of the articles were the underlying assumptions of their approaches discussed or causal mediation methods used. These results provide insights to how methodologists should aim to communicate methods, and motivation for more outreach to the research community on best practices for mediation analysis.

Functional Disabilities and Psychiatric Symptoms in Primary Progressive Aphasia.

OBJECTIVE: The aims of this study are to describe the chronology of functional disabilities in primary progressive aphasia (PPA), and to examine associations between psychiatric comorbidities and functional disabilities. METHODS: We conducted a retrospective data analysis using subjects enrolled at Alzheimer's Disease Research Centers between 2005 and 2019. Data were obtained from the National Alzheimer's Coordinating Center database. We included subjects whose primary diagnosis was PPA. Functional status was coded as a binary variable for the following functions: ambulation, transaction skills, verbal communication, meal preparation, and self-care. Behavioral data derived from the Neuropsychiatric Inventory Questionnaire. Descriptive statistics and cox proportional hazard analyses were used to characterize the emergence of disabilities and their association with psychiatric comorbidities. RESULTS: Data included 91 subjects with a clinical dementia rating scale of zero at baseline. At the initial visit, no individuals had impairments in self-care, while 7% had impairments in transactions, 3% in ambulation, and 2% in meal preparation. Ninety-three percent had language impairments at the onset of the study, and all by visit 4. By visit 5, 41% of patients had impairments in ambulation and in self-care, 49% were impaired in meal preparation and 70% had impairment in transactions. The presence of anxiety, depression, sleep disturbance and psychosis were all significantly associated with an increased risk for multiple functional disabilities. CONCLUSION: These findings provide clinicians with guidance for forecasting disabilities and targeting interventions in PPA.

Technology-assisted opioid education for out-of-treatment adults with opioid use disorder.

OBJECTIVE: To evaluate the feasibility and potential efficacy of a technology-assisted education program in teaching adults at a high risk of opioid overdose about opioids; opioid overdose; and opioid use disorder medications. METHOD: A within-subject, repeated-measures design was used to evaluate effects of the novel technology-assisted education program. Participants (N = 40) were out-of-treatment adults with opioid use disorder, recruited in Baltimore, Maryland from May 2019 to January 2020. The education program was self-paced and contained three courses. Each course presented information and required answers to multiple-choice questions. The education program was evaluated using a 50-item test, delivered before and after participants completed each course. Tests were divided into three subtests that contained questions from each course. We measured accuracy on each subtest before and after completion of each course and used a mixed-effects model to analyze changes in accuracy across tests. RESULTS: The technology-assisted education program required a median time of 91 min of activity to complete. Most participants completed the program in a single day. Accuracy on each subtest increased only after completion of the course that corresponded to that subtest, and learning comparisons were significant at the p < .001 level for all subtests. Accuracy on each subtest was unchanged before completion of the relevant course, and increases in accuracy were retained across subsequent tests. Learning occurred similarly independent of participant education, employment, and poverty. CONCLUSIONS: Technology-assisted education programs can provide at-risk adults with access to effective education on opioids, opioid overdose, and opioid use disorder medications. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Psychosocial Interventions to Promote Undetectable HIV Viral Loads: A Systematic Review of Randomized Clinical Trials.

Suppressing HIV viral loads to undetectable levels is essential for ending the HIV/AIDS epidemic. We evaluated randomized controlled trials aimed to increase antiretroviral medication adherence and promote undetectable viral loads among people living with HIV through November 22, 2019. We extracted data from 51 eligible interventions and analyzed the results using random effects models to compare intervention effects between groups within each intervention and across interventions. We also evaluated the relation between publication date and treatment effects. Only five interventions increased undetectable viral loads significantly. As a whole, the analyzed interventions were superior to Standard of Care in promoting undetectable viral loads. Interventions published more recently were not more effective in promoting undetectable viral loads. No treatment category consistently produced significant increases in undetectable viral loads. To end the HIV/AIDS epidemic, we should use interventions that can suppress HIV viral loads to undetectable levels.