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We consider a stochastic model, called the replicator coalescent, describing a system of blocks of k different types that undergo pairwise mergers at rates depending on the block types: with rate $C_{ij}\geq 0$ blocks of type i and j merge, resulting in a single block of type i. The replicator coalescent can be seen as a generalisation of Kingman’s coalescent death chain in a multi-type setting, although without an underpinning exchangeable partition structure. The name is derived from a remarkable connection between the instantaneous dynamics of this multi-type coalescent when issued from an arbitrarily large number of blocks, and the so-called replicator equations from evolutionary game theory. By dilating time arbitrarily close to zero, we see that initially, on coming down from infinity, the replicator coalescent behaves like the solution to a certain replicator equation. Thereafter, stochastic effects are felt and the process evolves more in the spirit of a multi-type death chain.
Recent changes in US government priorities have serious negative implications for science that will compromise the integrity of mental health research, which focuses on vulnerable populations. Therefore, as editors of mental science journals and custodians of the academic record, we confirm with conviction our collective commitment to communicating the truth.
The course of depression is heterogeneous. The employed treatment is a key element in the impact of the course of depression over the time. However, there is currently a gap of knowledge about the trajectories per treatment and related baseline factors. We aimed to identify trajectories of depressive symptoms and associated baseline characteristics for two treatment arms in a randomized clinical trial: treatment as usual (TAU) or TAU plus transdiagnostic group cognitive behavioral therapy (TAU + TDG-CBT).
Methods
Growth mixture modeling (GMM) was used to identify trajectories of depressive symptoms over 12 months post-treatment. Logistic regression models were used to examine associations between baseline characteristics and trajectory class membership in 483 patients (TAU: 231; TAU + TDG-CBT: 251).
Results
We identified different patterns of symptom change in the randomized groups: two trajectories in TAU (‘improvement’ (71.4%) and ‘no improvement’ (28.6%)), and four trajectories in TAU + TDG-CBT (‘recovery’ (69.8%), ‘late recovery’ (5.95%), ‘chronicity’ (4.77%), and ‘relapse’ (19.44%)). Higher baseline symptom severity and comorbidity were associated with poorer treatment outcomes in both treatment groups and worse emotional regulation strategies were linked to the ‘no improvement trajectory’ in TAU. The TAU + TDG-CBT group demonstrated greater symptom reduction compared to TAU alone.
Conclusions
There is heterogeneity in treatment outcomes. Integration of TDG-CBT with TAU significantly improves symptom reduction compared to TAU alone. Patients with higher baseline severity and comorbidities show poorer outcomes. Identification of trajectories and related factors could assist clinicians in tailoring treatment strategies to optimize outcomes, particularly for patients with a worse prognosis.
Improving functioning in adults with major depressive disorder (MDD) and bipolar disorder (BD) is a priority therapeutic objective.
Methods
This retrospective post hoc secondary analysis evaluated 108 patients with MDD or BD receiving the antidepressants vortioxetine, ketamine, or infliximab. The analysis aimed to determine if changes in objective or subjective cognitive function mediated the relationship between depression symptom severity and workplace outcomes. Cognitive function was measured by the Perceived Deficits Questionnaire (PDQ-5), the Digit Symbol Substitution Test (DSST), and the Trail Making Test Part B (TMT-B). Depression symptom severity was measured by the Montgomery–Åsberg Depression Rating Scale (MADRS). Workplace function was measured by the Sheehan Disability Scale (SDS) work–school item.
Results
When co-varying for BMI, age, and sex, the association between MADRS and SDS work scores was partially mediated by PDQ-5 total scores and DSST total scores, but not DSST error scores and TMT-B time.
Limitations
This study was insufficiently powered to perform sub-group analyses to identify distinctions between MDD and BD populations as well as between antidepressant agents.
Conclusions
These findings suggest that cognitive impairment in adults with MDD and BD is a critical mediator of workplace function and reinforces its importance as a therapeutic target.
Successfully educating urgent care patients on appropriate use and risks of antibiotics can be challenging. We assessed the conscious and subconscious impact various educational materials (informational handout, priming poster, and commitment poster) had on urgent care patients’ knowledge and expectations regarding antibiotics.
Design:
Stratified Block Randomized Control Trial.
Setting:
Urgent care centers (UCCs) in Colorado, Florida, Georgia, and New Jersey.
Participants:
Urgent care patients.
Methods:
We randomized 29 UCCs across six study arms to display specific educational materials (informational handout, priming poster, and commitment poster). The primary intention-to-treat (ITT) analysis evaluated whether the materials impacted patient knowledge or expectations of antibiotic prescribing by assigned study arm. The secondary as-treated analysis evaluated the same outcome comparing patients who recalled seeing the assigned educational material and patients who either did not recall seeing an assigned material or were in the control arm.
Results:
Twenty-seven centers returned 2,919 questionnaires across six study arms. Only 27.2% of participants in the intervention arms recalled seeing any educational materials. In our primary ITT analysis, no difference in knowledge or expectations of antibiotic prescribing was noted between groups. However, in the as-treated analysis, the handout and commitment poster were associated with higher antibiotic knowledge scores.
Conclusions:
Educational materials in UCCs are associated with increased antibiotic-related knowledge among patients when they are seen and recalled; however, most patients do not recall passively displayed materials. More emphasis should be placed on creating and drawing attention to memorable patient educational materials.
Principal components analysis can be redefined in terms of the regression of observed variables upon component variables. Two criteria for the adequacy of a component representation in this context are developed and are shown to lead to different component solutions. Both criteria are generalized to allow weighting, the choice of weights determining the scale invariance properties of the resulting solution. A theorem is presented giving necessary and sufficient conditions for equivalent component solutions under different choices of weighting. Applications of the theorem are discussed that involve the components analysis of linearly derived variables and of external variables.
In the continuous response (CR) task, the subject is given the name of a familiar category and must respond with category examples within a fixed time limit. The response sequence and the interresponse times are the measured variables. A general model is proposed for performance in the CR task. The time taken to generate a response is identified with the shortest search time from among a set of simultaneous search processes. Each response has a generation probability that is a function of the parameters governing the search process durations. Data involving the category “states in the United States” are used to test the model. The model accounts for the performance of nearly all individuals in these data.
An extension of component analysis to longitudinal or cross-sectional data is presented. In this method, components are derived under the restriction of invariant and/or stationary compositing weights. Optimal compositing weights are found numerically. The method can be generalized to allow differential weighting of the observed variables in deriving the component solution. Some choices of weightings are discussed. An illustration of the method using real data is presented.
Borsboom (Psychometrika, 71:425–440, 2006) noted that recent work on measurement invariance (MI) and predictive invariance (PI) has had little impact on the practice of measurement in psychology. To understand this contention, the definitions of MI and PI are reviewed, followed by results on the consistency between the two forms of invariance in the general case. The special parametric cases of factor analysis (strict factorial invariance) and linear regression analyses (strong regression invariance) are then described, along with findings on the inconsistency between the two forms of invariance in this context. Two numerical examples of inconsistency are reviewed in detail. The impact of violations of MI on accuracy of selection is illustrated. Finally, reasons for the slow dissemination of work on invariance are discussed, and the prospects for altering this situation are weighed.
Measurement invariance (lack of bias) of a manifest variable Y with respect to a latent variable W is defined as invariance of the conditional distribution of Y given W over selected subpopulations. Invariance is commonly assessed by studying subpopulation differences in the conditional distribution of Y given a manifest variable Z, chosen to substitute for W. A unified treatment of conditions that may allow the detection of measurement bias using statistical procedures involving only observed or manifest variables is presented. Theorems are provided that give conditions for measurement invariance, and for invariance of the conditional distribution of Y given Z. Additional theorems and examples explore the Bayes sufficiency of Z, stochastic ordering in W, local independence of Y and Z, exponential families, and the reliability of Z. It is shown that when Bayes sufficiency of Z fails, the two forms of invariance will often not be equivalent in practice. Bayes sufficiency holds under Rasch model assumptions, and in long tests under certain conditions. It is concluded that bias detection procedures that rely strictly on observed variables are not in general diagnostic of measurement bias, or the lack of bias.
Opioid antagonists block opioid receptors, a mechanism associated with utility in several therapeutic indications. Here, we review the sites of action, clinical uses, pharmacology, and general safety profiles of US Food and Drug Administration (FDA)-approved opioid antagonists. A review of the literature and product labels of opioid antagonists was conducted. The unique clinical uses of approved opioid antagonists are related to their ability to block opioid receptors centrally and/or peripherally. Centrally acting opioid antagonists treat opioid and alcohol use disorders (AUDs) and reverse opioid overdose. Because the opioid system influences weight and metabolism, one opioid antagonist combination product is approved for chronic weight management; another, approved for adults with schizophrenia or bipolar I disorder, mitigates olanzapine-associated weight gain. Peripherally acting opioid antagonists are approved for opioid-induced constipation; another accelerates gastrointestinal recovery after bowel surgery. Opioid antagonists are generally well tolerated; they are not associated with physiologic dependence or abuse. However, opioid antagonists can precipitate acute opioid withdrawal in patients using or undergoing withdrawal from opioid agonists. Likewise, their use can confer a risk for opioid overdose if attempts are made to overcome opioid antagonist blockade of opioid receptors via the intake of additional opioids. Opioid receptor antagonists have diverse therapeutic benefits based on their respective pharmacology and sites of action; understanding their respective nuances facilitates the safe and effective use of these agents.
The purpose of this study is to examine the national impact of workplace factors during the SARS-CoV-2 pandemic on mental health experienced by non-physician healthcare workers (HCWs).
Methods
This study consisted of an online sample of non-physician HCWs across the United States, including nurses, medical assistants, and physician assistants. The survey consisted of 93 questions, which included the Perceived Stress Scale, the Center for Epidemiological Studies-Depression (CESD-10) scale, questions about COVID-19 vaccination, sources of trusted information, and questions about work environment and training during the COVID-19 pandemic. Descriptive statistics were used to evaluate associations.
Results
In the final sample (N = 220), (81.8%) reported receiving at least one dose of a COVID vaccine. Most respondents trusted the CDC’s information on the SARS-CoV-2 virus and COVID-19 disease. Several workplace-related factors that occurred during the pandemic were associated with moderate to high levels of perceived stress, fatigue, and higher risk of developing depression. In particular, concerns about exposing others, experiencing discrimination related to their jobs, and caring for patients who died from COVID-19 were associated with increased perceived stress, depression, and fatigue.
Conclusions
The importance of planning by healthcare facilities should include planning for workplace factors associated with poor mental health among all HCWs.
To compare time to relapse in patients with major depressive disorder (MDD) stabilised on antidepressant treatment (ADT) + brexpiprazole who were randomised to continued adjunctive brexpiprazole or brexpiprazole withdrawal (switch to placebo).
Methods:
This Phase 3, multicentre, double-blind, placebo-controlled, parallel-arm, randomised withdrawal study enrolled adults with MDD and inadequate response to 2–3 ADTs. All patients started on adjunctive brexpiprazole 2–3 mg/day (Phase A, 6–8 weeks). Patients whose symptoms stabilised (Phase B, 12 weeks) were randomised 1:1 to adjunctive brexpiprazole or adjunctive placebo (Phase C, 26 weeks). The primary endpoint was time to relapse in Phase C. Depression rating scale score changes were secondary endpoints.
Results:
1149 patients were enrolled and 489 patients were randomised (ADT + brexpiprazole n = 240; ADT + placebo n = 249). Median time to relapse was 63 days from randomisation in both treatment groups for patients who received ≥1 dose. Relapse criteria were met by 22.5% of patients (54/240) on ADT + brexpiprazole and 20.6% (51/248) on ADT + placebo (hazard ratio, 1.14; 95% confidence interval, 0.78–1.67; p = 0.51, log-rank test). Depression scale scores improved during Phases A–B and were maintained in Phase C. Mean weight increased by 2.2 kg in Phases A–B and stabilised in Phase C.
Conclusion:
Time to relapse was similar between continued adjunctive brexpiprazole and brexpiprazole withdrawal; in both groups, ∼80% of stabilised patients remained relapse free at their last visit. Adjunctive brexpiprazole therapy was generally well tolerated over up to 46 weeks, with minimal adverse effects following brexpiprazole withdrawal.
Plant-derived proteins are often deficient in essential amino acids and have lower rates of digestibility than animal-derived proteins. Blending different plant-derived proteins could compensate for these deficiencies and may augment postprandial aminoacidemia over single-source plant proteins. This study assessed plasma amino acids and appetite hormones, appetite sensations and ad libitum energy intake following ingestion of a pea-rice protein blend (BLEND), compared with pea-only (PEA) and whey (WHEY) protein. In a randomised, double-blind, crossover design, ten healthy adults (M n 4, F n 6; mean (sd) age 22 (sd 3) years; BMI 24 (sd 3) kg·m2) ingested 0·3 g·kg·body mass–1 of BLEND, PEA or WHEY. Arterialised venous blood samples and appetite ratings were obtained in the fasted state and over 240 min postprandially. Energy intake was measured via an ad libitum buffet-style test meal. Mean plasma essential amino acid incremental AUC was higher in WHEY, compared with PEA (P < 0·01; mean diff (95 % CI): 44 218 (15 806, 72 631) μmol·240 min·l–1) and BLEND (P < 0·01; 14 358 (16 031, 101 121) μmol·240 min·l–1), with no differences between PEA and BLEND (P = 0·67). Plasma ghrelin and glucagon-like peptide-1, appetite ratings and ad libitum energy intake responses did not differ between treatments (P > 0·05 for all). Ingestion of a pea-rice protein blend did not augment postprandial aminoacidemia above pea protein, perhaps attributable to marginal differences in essential amino acid composition. No between-treatment differences in appetite or energy intake responses were apparent, suggesting that the influence of protein ingestion on perceived appetite ratings and orexigenic hormonal responses may not be solely determined by postprandial plasma aminoacidemia.
Seclusion is a restrictive practice that many healthcare services are trying to reduce. Previous studies have sought to identify predictors of seclusion initiation, but few have investigated factors associated with adverse outcomes after seclusion termination.
Aims
To assess the factors that predict an adverse outcome within 24 h of seclusion termination.
Method
In a cohort study of individuals secluded in psychiatric intensive care units, we investigated factors associated with any of the following outcomes: actual violence, attempted violence, or reinitiation of seclusion within 24 h of seclusion termination. Among the seclusion episodes that were initiated between 29 March 2018 and 4 March 2019, we investigated the exposures of medication cooperation, seclusion duration, termination out of working hours, involvement of medical staff in the final seclusion review, lack of insight, and agitation or irritability. In a mixed-effects logistic regression model, associations between each exposure and the outcome were calculated. Odds ratios were calculated unadjusted and adjusted for demographic and clinical variables.
Results
We identified 254 seclusion episodes from 122 individuals (40 female, 82 male), of which 106 (41.7%) had an adverse outcome within 24 h of seclusion termination. Agitation or irritability was associated with an adverse outcome, odds ratio 1.92 (95% CI 1.03 to 3.56, P = 0.04), but there was no statistically significant association with any of the other exposures, although confidence intervals were broad.
Conclusions
Agitation or irritability in the hours preceding termination of seclusion may predict an adverse outcome. The study was not powered to detect other potentially clinically significant factors.
We extend the work of Ivancovsky et al. by proposing that in addition to novelty seeking, mood regulation goals – including enhancing positive mood and repairing negative mood – motivate both creativity and curiosity. Additionally, we discuss how the effects of mood on state of mind are context-dependent (not fixed), and how such flexibility may impact creativity and curiosity.
Changing practice patterns caused by the pandemic have created an urgent need for guidance in prescribing stimulants using telepsychiatry for attention-deficit hyperactivity disorder (ADHD). A notable spike in the prescribing of stimulants accompanied the suspension of the Ryan Haight Act, allowing the prescribing of stimulants without a face-to-face meeting. Competing forces both for and against prescribing ADHD stimulants by telepsychiatry have emerged, requiring guidelines to balance these factors. On the one hand, factors weighing in favor of increasing the availability of treatment for ADHD via telepsychiatry include enhanced access to care, reduction in the large number of untreated cases, and prevention of the known adverse outcomes of untreated ADHD. On the other hand, factors in favor of limiting telepsychiatry for ADHD include mitigating the possibility of exploiting telepsychiatry for profit or for misuse, abuse, and diversion of stimulants. This Expert Consensus Group has developed numerous specific guidelines and advocates for some flexibility in allowing telepsychiatry evaluations and treatment without an in-person evaluation to continue. These guidelines also recognize the need to give greater scrutiny to certain subpopulations, such as young adults without a prior diagnosis or treatment of ADHD who request immediate-release stimulants, which should increase the suspicion of possible medication diversion, misuse, or abuse. In such cases, nonstimulants, controlled-release stimulants, or psychosocial interventions should be prioritized. We encourage the use of outside informants to support the history, the use of rating scales, and having access to a hybrid model of both in-person and remote treatment.
Cardiometabolic disease risk factors are disproportionately prevalent in bipolar disorder (BD) and are associated with cognitive impairment. It is, however, unknown which health risk factors for cardiometabolic disease are relevant to cognition in BD. This study aimed to identify the cardiometabolic disease risk factors that are the most important correlates of cognitive impairment in BD; and to examine whether the nature of the relationships vary between mid and later life.
Methods
Data from the UK Biobank were available for 966 participants with BD, aged between 40 and 69 years. Individual cardiometabolic disease risk factors were initially regressed onto a global cognition score in separate models for the following risk factor domains; (1) health risk behaviors (physical activity, sedentary behavior, smoking, and sleep) and (2) physiological risk factors, stratified into (2a) anthropometric and clinical risk (handgrip strength, body composition, and blood pressure), and (2b) cardiometabolic disease risk biomarkers (CRP, lipid profile, and HbA1c). A final combined multivariate regression model for global cognition was then fitted, including only the predictor variables that were significantly associated with cognition in the previous models.
Results
In the final combined model, lower mentally active and higher passive sedentary behavior, higher levels of physical activity, inadequate sleep duration, higher systolic and lower diastolic blood pressure, and lower handgrip strength were associated with worse global cognition.
Conclusions
Health risk behaviors, as well as blood pressure and muscular strength, are associated with cognitive function in BD, whereas other traditional physiological cardiometabolic disease risk factors are not.