Real-time cognitive performance and positive symptom expression in schizophrenia.

Deficits in cognitive functions are frequent in schizophrenia and are often conceptualized as stable characteristics of this disorder. However, cognitive capacities may fluctuate over the course of a day and it is unknown if such variation may be linked to the dynamic expression of psychotic symptoms. This investigation used Ecological Momentary Assessment (EMA) to provide mobile tests of cognitive functions and positive symptoms in real time. Thirty-three individuals with schizophrenia completed five EMA assessments per day for a one-week period that included real-time assessments of cognitive performance and psychotic symptoms. A subsample of patients and 31 healthy controls also completed a functional MRI examination. Relative to each individual's average score, moments of worsened cognitive performance on the mobile tests were associated with an increased probability of positive symptom occurrence over subsequent hours of the day (coef = 0.06, p < 0.05), adjusting for the presence of psychotic symptoms at the moment of mobile test administration. These prospective associations varied as a function of graph theory indices in MRI analyses. These findings demonstrate that cognitive performance is prospectively linked to psychotic symptom expression in daily life, and that underlying brain markers may be observed in the Executive Control Network. While the potential causal nature of this association remains to be investigated, our results offer promising prospects for a better understanding of the underlying mechanisms of symptom expression in schizophrenia.

Prior depression predicts greater stress during Covid-19 mandatory lockdown among college students in France.

BACKGROUND: The Covid-19 pandemic and its related public health measures such as mandatory lockdowns have been shown to have an impact on mental health. A key question is the role of pre-existing psychiatric disorders in how such measures are experienced. METHODS: During the first country-wide lockdown imposed in France, a Covid-19 module was added to the French portion of the ongoing World Mental Health International college student survey. The present study focuses on respondents who completed the survey during that time frame (n = 291). RESULTS: Students with prior depression endorsed greater increases in anxiety (72.2% vs 50.9%) and stress (72.2% vs 49.4%), as well as greater decreases in concentration (87.0% vs 72.9%) during lockdown as compared to those without depression history. In multivariate analyses, prior depression was associated with overall stress (AOR = 5.50), financial stress (AOR = 1.95), family stress (AOR = 2.47), work related stress (AOR = 5.15), and stress related to loved ones (AOR = 2.21). Prior depression was also associated with greater probability experiencing increased anxiety (AOR = 2.61) and stress (AOR = 2.55) during lockdown. CONCLUSIONS: The findings indicate that the best predictor of experiencing stress and anxiety during the first Covid-19 lockdown was a history of depression prior to the pandemic outbreak. Implementing public health measures such as mandatory national lockdowns should be accompanied by strategies for reaching out to those who are vulnerable due to a history of mental illness.

Remote Digital Psychiatry for Mobile Mental Health Assessment and Therapy: MindLogger Platform Development Study.

BACKGROUND: Universal access to assessment and treatment of mental health and learning disorders remains a significant and unmet need. There are many people without access to care because of economic, geographic, and cultural barriers, as well as the limited availability of clinical experts who could help advance our understanding and treatment of mental health. OBJECTIVE: This study aims to create an open, configurable software platform to build clinical measures, mobile assessments, tasks, and interventions without programming expertise. Specifically, our primary requirements include an administrator interface for creating and scheduling recurring and customized questionnaires where end users receive and respond to scheduled notifications via an iOS or Android app on a mobile device. Such a platform would help relieve overwhelmed health systems and empower remote and disadvantaged subgroups in need of accurate and effective information, assessment, and care. This platform has the potential to advance scientific research by supporting the collection of data with instruments tailored to specific scientific questions from large, distributed, and diverse populations. METHODS: We searched for products that satisfy these requirements. We designed and developed a new software platform called MindLogger, which exceeds the requirements. To demonstrate the platform's configurability, we built multiple applets (collections of activities) within the MindLogger mobile app and deployed several of them, including a comprehensive set of assessments underway in a large-scale, longitudinal mental health study. RESULTS: Of the hundreds of products we researched, we found 10 that met our primary requirements with 4 that support end-to-end encryption, 2 that enable restricted access to individual users' data, 1 that provides open-source software, and none that satisfy all three. We compared features related to information presentation and data capture capabilities; privacy and security; and access to the product, code, and data. We successfully built MindLogger mobile and web applications, as well as web browser-based tools for building and editing new applets and for administering them to end users. MindLogger has end-to-end encryption, enables restricted access, is open source, and supports a variety of data collection features. One applet is currently collecting data from children and adolescents in our mental health study, and other applets are in different stages of testing and deployment for use in clinical and research settings. CONCLUSIONS: We demonstrated the flexibility and applicability of the MindLogger platform through its deployment in a large-scale, longitudinal, mobile mental health study and by building a variety of other mental health-related applets. With this release, we encourage a broad range of users to apply the MindLogger platform to create and test applets to advance health care and scientific research. We hope that increasing the availability of applets designed to assess and administer interventions will facilitate access to health care in the general population.

Feasibility and validity of Ecological Momentary Assessment in patients with acute coronary syndrome.

BACKGROUND: In recent years, Ecological Momentary Assessment (EMA) has expanded rapidly in healthcare research but its application specifically to the field of cardiology has been limited. This study presents essential information concerning the feasibility and validity of EMA in patients with acute coronary syndrome. METHODS: Four months after a first-ever acute coronary syndrome, 47 patients completed EMA five times a day for seven consecutive days concerning their current activities, mood and perceived negativity or positivity of daily events. RESULTS: Compliance with the repeated electronic assessments was high, and no evidence was found for time-dependent biases such as fatigue or practice effects. The resulting EMA data were found to have high internal validity, high reliability when considering average scores, and low reliability when considering within-person variance. CONCLUSIONS: We found evidence for the feasibility and intrinsic validity of EMA in patients with acute coronary syndrome. Research examining daily life experiences, symptoms and therapeutic adherence in this population can be reinforced through the use of mobile technologies.

Stress and anxiety among university students in France during Covid-19 mandatory confinement.

While necessary from a public health standpoint, Covid-19 confinement strategies are often contrary to evidence-based therapies used to treat mental disorders. University students may be particularly vulnerable to mental health problems, but recent studies have indicated only a negligible impact of confinement strategies. French respondents to a World Mental Health survey of university students completed questions concerning Covid-19 confinement. The sample experienced increased anxiety as well as moderate to severe stress during confinement. Respondents who did not relocate to live with parents were disproportionately affected. Knowledge of confinement effects may be used to reduce its negative impact in vulnerable populations.

Feasibility and validity of mobile cognitive testing in patients with substance use disorders and healthy controls.

BACKGROUND AND OBJECTIVES: Mobile testing of executive deficits in substance-related addictions is highly novel but requires validation. METHODS: Sixty-one individuals (34 patients, 27 healthy controls) completed Ecological Momentary Assessments with mobile executive tests. RESULTS: Compliance with the tests was high (78% to 91%) in both the patient and control groups. No fatigue effects were detected, practice effects were observed for controls only, and convergent validity was found relative to neuropsychological assessments. Conclusions The use of mobile cognitive testing is feasible and valid in this population. Scientific Significance Mobile cognitive tests provide new opportunities for both research and clinical intervention. (Am J Addict 2018;27:553-556).

Moment-to-moment associations between negative affect, aberrant salience, and paranoia.

INTRODUCTION: There is an ongoing debate about whether negative affect are consequences or triggers of paranoid thinking. It has also been suggested that aberrant salience is central to the development of delusions. This study modelled the moment-to-moment relationships between negative affect, aberrant salience, and paranoia in acute inpatients with psychosis. METHODS: Participants with active paranoid delusions were assessed using clinical rating scales and experience sampling method (ESM) over 14 days. ESM data were analysed using time-lagged multilevel regression modelling. RESULTS: Both negative affect and aberrant salience predicted an increase in paranoia at the next time point. Conversely, the level of paranoia did not predict subsequent changes in negative affect or aberrant salience. Negative affect predicted an increase in aberrant salience at the next time point, and vice versa. CONCLUSIONS: Negative affect and aberrant salience appear to drive and exacerbate paranoia, rather than being merely the sequelae of the symptom. Our results suggest both direct and indirect (via aberrant salience) pathways from negative affect to paranoia.

Feasibility and Acceptability of Ecological Momentary Assessment of Daily Functioning Among Older Adults with HIV.

OBJECTIVE: This study aimed to examine the feasibility, acceptability, and initial validity of using smartphone-based ecological momentary assessment (EMA) to assess daily functioning and other behavioral factors among older HIV+ adults. METHODS: Twenty older HIV+ adults (mean age: 59 years) completed laboratory-based neurobehavioral and functional assessments then completed EMA surveys via smartphones five times per day for one week. RESULTS: Excellent EMA adherence (86.4%) was found, and participants rated their experience with EMA methods positively. Time-use data indicated participants were spending 74% of their waking-sampled time at home, 63% of their time alone, and 32% of their time engaged in passive leisure activities (e.g., watching TV). Better neurocognitive and functional capacity abilities were correlated with less time spent in passive leisure activities. Lastly, mood and cognitive symptom data collected via EMA were significantly associated with scores from laboratory-based assessments of these same constructs. CONCLUSIONS: EMA via smartphones is a feasible and acceptable data collection method among older HIV+ adults and appears to be a promising mobile tool to assess daily functioning behaviors in HIV. These preliminary findings indicate older HIV+ adults are spending a considerable amount of time at home, alone, and engaged in passive leisure activities, primarily watching TV. EMA may contribute to future research examining functional disability among the growing population of older HIV+ adults.

Very early social support following mild stroke is associated with emotional and behavioral outcomes three months later.

OBJECTIVE: To investigate whether social contact and support received during hospitalization for acute ischemic stroke predict depression and daily life functioning three months later. DESIGN: Prospective observational study using Ecological Momentary Assessments to evaluate the number of social contacts as well as social support received from family, friends and medical staff within 24 hours following admission for stroke. Patients also monitored depression symptoms and behavior in real-time and in daily life contexts three months later. SETTING: A university hospital acute stroke unit. SUBJECTS: Thirty-four mild ischemic stroke patients. INTERVENTIONS: None. MAIN MEASURES: One-day Ecological Momentary Assessments immediately following stroke collected information concerning perceived social support, number of social contacts and depression symptoms. Ecological Momentary Assessments was repeated three months later and addressed depression levels as well as activities of daily living, such as working, cooking, shopping and housework. RESULTS: The number of social interactions received at hospitalization did not predict three-month outcomes. However, a better quality of moral support from friends and family immediately after stroke was associated with decreases in later depression levels ( p = 0.041) and increases in activities of daily living ( p = 0.011). Material support from friends and family was associated with increases in activities of daily living ( p = 0.012). No effect was observed for support received from medical staff. CONCLUSIONS: Patient perceptions of better support quality, and not quantity, immediately following mild stroke, are associated with better behavioral and emotional outcomes three months later.

Affective Prosody and Depression After Stroke: A Pilot Study.

BACKGROUND AND PURPOSE: Poststroke depression (PSD) is a frequent complication of stroke with detrimental consequences in terms of quality of life and functional outcomes. In individuals with major depression, several studies have demonstrated an alteration of affective prosody. The aim of this study is to identify prosodic markers that may be predictive of PSD. METHODS: Patient voices were recorded at baseline and 3 months after stroke. We extracted prosodic parameters, including fundamental frequency, percentage of voice breaks, and shimmer. Depression and anxiety symptoms were assessed 3 months later. RESULTS: Among the 49 patients included in the study, 22.5% developed PSD 3 months after stroke. A significant decrease was observed concerning the fundamental frequency among patients who developed PSD. Discriminant analysis demonstrated that initial voice breaks coupled with shimmer are strongly predictive of subsequent PSD. CONCLUSIONS: Early alterations of affective prosody are associated with a higher risk of PSD 3 months after a stroke. This new physiological approach overcomes traditional barriers associated with clinical instruments and contributes to the prediction of this disorder.

Gender and stress in predicting depressive symptoms following stroke.

BACKGROUND: Post-stroke depression (PSD) is associated with poor clinical and functional outcomes, and women are likely to experience PSD more than men. Although stress is related to depression, and women report greater emotional reactivity to stressful life events, the link between stress and gender is yet to be examined relative to PSD. Further, electronic momentary assessment (EMA), a mobile technology, has not been used to assess stressful life events and PSD in real time and in the natural environments of daily life. The purpose of the current study was to examine gender differences in the relationship of stress and PSD using EMA. METHODS: Individuals admitted to the Stroke Center at the University of Bordeaux were contacted for participation in a prospective study of symptoms and experiences in daily life using ambulatory monitoring. Forty-three post-stroke patients (47% female) completed electronic assessments of life events, perceived stress, and depressive symptoms (i.e., sad mood, anhedonia, fatigue, concentration difficulties, appetite change, negative thoughts, hopelessness) during their daily life for one week. Patients also completed a clinician-administered standardized depression scale at baseline and three-month follow-up. RESULTS: Using EMA, participants responded to 83.7% of the electronic interviews for a total of 1,140 observations across diverse daily life contexts. Stressful events of any degree of negativity were reported at over one-third (37.3%) of all EMA assessments. The severity of depressive symptoms as assessed in daily life through EMA was greater in women following stroke than in men. Further, there was a significant association between EMA-assessed depressive symptoms and daily life stress for women, but not men. This association was due primarily to three specific depressive symptoms: sad mood, fatigue, and appetite change. No difference was observed between men and women in standardized depression assessments administered during clinic visits at baseline or three-month follow-up. CONCLUSIONS: Greater reactivity to stressful life events and a link between stress reactivity and depressive symptoms were found in female as compared to male post-stroke patients. Gender differences in depressive symptoms were identified using EMA data collected during daily life as contrasted with the use of a standard assessment during clinic visits. Mobile technologies may help to identify important real-time behaviors and symptoms that are not observable by standard clinical assessments employed at regular clinic visits. Further, future research should examine the overall and gender-specific benefits of stress-based interventions to reduce the risk of PSD for adults.

Anxiety and 10-year risk of incident and recurrent depressive symptomatology in older adults.

BACKGROUND: Anxiety has been shown to often precede depression in children and young adults. Only a small number of investigations have examined this form of comorbidity in older adults and the temporal relationship of these syndromes remains unclear. The objective was to verify whether trait anxiety predicts incident/recurrent depressive symptomatology in older adults independently of variables susceptible to explain this relationship in this population, such as cognitive complaints, subjective health, and baseline depressive symptoms. METHODS: A random sample of 4,649 individuals aged 65 years or older from the Three-City Study, a prospective longitudinal study with a 10-year follow-up, was used. Incident and recurrent depressive symptomatology were determined by Center for Epidemiological Studies Depression Scale cutoff scores. Anxiety was measured using the trait scale of the State-Trait Anxiety Inventory. Cox proportional hazards models were used to determine the independent risk of depressive symptomatology for baseline anxiety, cognitive complaints, subjective health, and depressive symptoms, adjusting for sociodemographic, mental health, and physical health covariates. RESULTS: Incident depressive symptomatology was independently predicted by baseline anxiety, depressive symptoms, cognitive complaints, and subjective health. Recurrent depressive symptomatology was independently predicted by baseline anxiety and depressive symptoms, but not by cognitive complaints and subjective health. Anxiety was associated with a higher risk of incident depressive symptomatology only in participants without a history of a major depressive episode, and with a higher risk of recurrent depressive symptomatology in men than in women. CONCLUSIONS: Trait anxiety constitutes an important independent risk factor for subsequent depressive symptomatology in older adults.

Daily life behaviors and depression risk following stroke: a preliminary study using ecological momentary assessment.

Approximately one-third of stroke survivors have symptoms of depression. A better understanding of the early risk factors implicated in this form of comorbidity may contribute to the development of early prevention strategies and to improving outcomes for this population. The current study uses ecological momentary assessment techniques to identify behavioral risk factors for depression 3 months after stroke. Thirty-six participants completed ambulatory monitoring of daily life circumstances (location, social environment, and activity) 5 times per day during a 1-week period after hospital discharge. Clinician-administered measures of depression were also provided before discharge and 3 months later. Ambulatory monitoring revealed that depression scores at 3 months were lower among individuals with more social interactions but higher among those who reported having sports activities and working in the week following hospital discharge. Daily life behaviors may have important implications for understanding the risk of poststroke depression, and mobile technologies may provide important contributions to their investigation.

Mood Variability, Craving, and Substance Use Disorders: From Intrinsic Brain Network Connectivity to Daily Life Experience.

BACKGROUND: Substance use disorders (SUDs) are major contributors to morbidity and mortality rates worldwide, and this global burden is attributable in large part to the chronic nature of these conditions. Increased mood variability might represent a form of emotional dysregulation that may have particular significance for the risk of relapse in SUD, independent of mood severity or diagnostic status. However, the neural biomarkers that underlie mood variability remain poorly understood. METHODS: Ecological momentary assessment was used to assess mood variability, craving, and substance use in real time in 54 patients treated for addiction to alcohol, cannabis, or nicotine and 30 healthy control subjects. Such data were jointly examined relative to spectral dynamic causal modeling of effective brain connectivity within 4 networks involved in emotion generation and regulation. RESULTS: Differences in effective connectivity were related to daily life variability of emotional states experienced by persons with SUD, and mood variability was associated with craving intensity. Relative to the control participants, effective connectivity was decreased for patients in the prefrontal control networks and increased in the emotion generation networks. Findings revealed that effective connectivity within the patient group was modulated by mood variability. CONCLUSIONS: The intrinsic causal dynamics in large-scale neural networks underlying emotion regulation play a predictive role in a patient's susceptibility to experiencing mood variability (and, subsequently, craving) in daily life. The findings represent an important step toward informing interventional research through biomarkers of factors that increase the risk of relapse in persons with SUD.

Craving dynamics and related cerebral substrates predict timing of use in alcohol, tobacco, and cannabis use disorders.

Background: Patients treated for Substance Use Disorders exhibit highly fluctuating patterns of craving that could reveal novel prognostic markers of use. Accordingly, we 1) measured fluctuations within intensively repeated measures of craving and 2) linked fluctuations of craving to connectivity indices within resting-state (rs) brain regions to assess their relation to use among patients undergoing treatment for Alcohol, Tobacco and Cannabis Use Disorders. Method: Participants -64 individuals with SUD for tobacco, alcohol, or cannabis and 35 healthy controls-completed a week of Ecological Momentary Assessment (EMA) during which they reported craving intensity and substance use five times daily. Before EMA, a subsample of 50 patients, and 34 healthy controls also completed resting-state (rs)-MRI acquisitions. Craving temporal dynamics within each day were characterized using Standard Deviation (SD), Auto-Correlation Factor (ACF), and Mean Successive Square Difference (MSSD). Absolute Difference (AD) in craving between assessments was a prospective prediction measure. Results: Within-day, higher MSSD predicted greater substance use while controlling for mean craving. Prospectively higher AD predicted later increased substance use independently of previous use or craving level. Moreover, MSSD was linked to strength in five functional neural connections, most involving frontotemporal systems. Cerebello-thalamic and thalamo-frontal connectivity were also linked to substance use and distinguished the SUD from the controls. Conclusion: To the best of our knowledge, this is the first study to indicate that instability in craving may be a trigger for use in several SUD types, beyond the known effect of craving intensity.

Predictors of medication adherence in a large 1-year prospective cohort of individuals with schizophrenia: insights from the multicentric FACE-SZ dataset.

Schizophrenia is characterized by the most salient medication adherence problems among severe mental disorders, but limited prospective data are available to predict and improve adherence in this population. This investigation aims to identify predictors of medication adherence over a 1-year period in a large national cohort using clustering analysis. Outpatients were recruited from ten Schizophrenia Expert Centers and were evaluated with a day-long standardized battery including clinician and patient-rated medication adherence measures. A two-step cluster analysis and multivariate logistic regression were conducted to identify medication adherence profiles based on the Medication Adherence rating Scale (MARS) and baseline predictors. A total of 485 participants were included in the study and medication adherence was significantly improved at the 1-year follow-up. Higher depressive scores, lower insight, history of suicide attempt, younger age and alcohol use disorder were all associated with poorer adherence at 1 year. Among the 203 patients with initially poor adherence, 86 (42%) switched to good adherence at the 1-year follow-up, whereas 117 patients (58%) remained poorly adherent. Targeting younger patients with low insight, history of suicide, alcohol use disorder and depressive disorders should be prioritized through literacy and educational therapy programs. Adherence is a construct that can vary considerably from year to year in schizophrenia, and therefore may be amenable to interventions for its improvement. However, caution is also warranted as nearly one in five patients with initially good adherence experienced worsened adherence 1 year later.

Transitions to regular smoking and nicotine dependence in the Adolescent National Comorbidity Survey (NCS-A).

OBJECTIVE: This study aims to investigate the occurrence of nicotine dependence following the achievement of previous smoking milestones (initiation, weekly, and daily smoking). METHOD: Analyses are based on data from The National Comorbidity Survey-Adolescent, a nationally representative face-to-face survey of 10,123 adolescents (age 13-17) conducted between 2001 and 2004. RESULTS: Among adolescents who had ever smoked (36.0%), 40.7% reached weekly smoking levels and 32.8% had reached daily smoking. Approximately one in five adolescents who had ever smoked (19.6%) met criteria for nicotine dependence. An earlier age of smoking initiation, a shorter time since the onset of smoking and faster transitions among smoking milestones were independently associated with the onset of daily smoking and nicotine dependence. CONCLUSIONS: These findings shed new light on the course of smoking and nicotine dependence during adolescence by demonstrating a rapid transition across smoking stages for those most at risk for the development of chronic and dependent use.

Evolution of depression symptoms following stroke: a prospective study using computerized ambulatory monitoring.

BACKGROUND: Despite the high prevalence and impact of post-stroke depression (PSD), questions persist concerning the nature and stability of PSD over time. The current study uses state-of-the-art computerized ambulatory monitoring techniques to assess daily life depression symptoms following stroke and examines the evolution of depression levels over a three-month period. METHODS: 48 patients admitted to a university hospital neurology unit for ischemic or hemorrhagic stroke participated in ambulatory monitoring of DSM-IV depression symptoms for a one-week period after hospital discharge. Clinician-administered measures of depression were also obtained at discharge and again three months later. RESULTS: The percentage of the sample with elevated depression scores was the same at discharge and three months later, but consistency in depression profiles was low. Ambulatory monitoring revealed that elevated depression levels at hospital discharge were most strongly associated with anhedonia (t ratio = 4.840, p < 0.001) and fatigue (t ratio = 4.00, p < 0.001), whereas individuals with elevated scores at three months were predicted by daily life negative thoughts (t ratio = 4.051, p < 0.001), anxious mood (t ratio = 3.489, p < 0.01), sad mood (t ratio = 2.621, p < 0.05) and emotional reactivity (t ratio = 2.466, p < 0.05). CONCLUSIONS: The prevalence of depression may appear stable during the immediate weeks and months following stroke, but it is likely to be composed of very different symptom profiles. The immediate physical and psychological impact of stroke may induce somatic symptoms that explain elevated depression levels and which may not indicate a risk factor for later depression.

Emotional hyperreactivity as a core dimension of manic and mixed states.

Despite its obvious importance in mood disorders, characterization of emotional reactivity has been neglected in bipolar disorders. Concerning manic states and the current classification, the main criterion is the presence of an elevated or expansive mood. In contrast to this characteristic and often prolonged mood state, emotional reactivity refers to a brief evoked response to salient emotional stimuli. The goal of this study was to assess the intensity of emotional responses triggered by viewing slides in bipolar patients with manic or mixed states. Our hypothesis was that all emotional responses are exacerbated, whatever the valence of the stimuli. We compared 33 patients with manic or mixed states with 33 matched euthymic patients and 33 healthy control subjects. Arousal and attribution of valence were assessed while subjects viewed slides taken from the International Affective Picture System (positive, neutral and negative slides). Patients with manic or mixed states reported a higher arousal when viewing all types of slides in comparison with the other groups. Concerning attribution of valence, patients with manic or mixed states assessed neutral slides as more pleasant. When bipolar patients with manic and mixed states are placed in front of positive, neutral and negative slides, the slides trigger a higher intensity of emotions, whatever the valence of the emotional stimuli. These results strengthen the importance of emotional hyperreactivity as a core dimension in manic and mixed states in bipolar disorder.

The role of alcohol consumption in female victimization: findings from a French representative sample.

Alcohol is frequently related to interpersonal aggression, but information regarding the role of alcohol consumption by victims of severe aggression is however lacking. In order to better understand the dynamic of victimization, we investigated contextual, facilitator, and psychological impact variables related to victimization in a French sample composed of 1,033 females aged 18-74 years. The participants were recruited using quota sampling methodology, and responses were measured using Computer-Assisted Self-Interviewer. A logistic regression was conducted using a backward elimination procedure to identify the significant predictors of blows and wounds suffered in the past 24 months. The results indicated that victims, relative to nonvictims, did binge drink significantly more often, had a higher aggression trait, and had experienced more social hardships in the past. The study's limitations are noted.