The Use of Text Messaging as an Adjunct to Internet-Based Cognitive Behavioral Therapy for Major Depressive Disorder in Youth: Secondary Analysis.

BACKGROUND: As an established treatment for major depressive disorder (MDD), cognitive behavioral therapy (CBT) is now implemented and assessed in internet-based formats that, when combined with smartphone apps, enable secure text messaging. As an adjunct to such internet-based CBT (ICBT) approaches, text messaging has been associated with increased adherence and therapeutic alliance. OBJECTIVE: This study analyzed data from the intervention arm of a randomized control trial evaluating 24-week ICBT for MDD (intervention arm) against standard-care psychiatry (waitlist control). The aim of this secondary analysis was to assess MDD symptom improvement in relation to the frequency and content of text messages sent by ICBT participants to Navigator-Coaches during randomized control trial participation. Higher text frequency in general and in 3 conceptual categories (appreciating alliance, alliance building disclosures, and agreement confirmation) was hypothesized to predict larger MDD symptom improvement. METHODS: Participants were young adults (18-30 years) from the Centre for Addiction and Mental Health. The frequencies of categorized texts from 20 ICBT completers were analyzed with respect to MDD symptom improvement using linear regression models. Texts were coded by 2 independent coders and categorized using content analysis. MDD symptoms were measured using the Beck Depression Inventory-II (BDI-II). RESULTS: Participants sent an average of 136 text messages. Analyses indicated that BDI-II improvement was negatively associated with text messaging frequency in general (ß=-0.029, 95% CI -0.11 to 0.048) and in each of the 3 categories: appreciating alliance (ß=-0.096, 95% CI -0.80 to 0.61), alliance building disclosures (ß=-0.098, 95% CI -0.28 to 0.084), and agreement confirmation (ß=-0.076, 95% CI -0.40 to 0.25). Altogether, the effect of text messaging on BDI-II improvement was uniformly negative across statistical models. More text messaging appeared associated with less MDD symptom improvement. CONCLUSIONS: The hypothesized positive associations between conceptually categorized text messages and MDD symptom improvement were not supported in this study. Instead, more text messaging appeared to indicate less treatment benefit. Future studies with larger samples are needed to discern the optimal use of text messaging in ICBT approaches using adjunctive modes of communication. TRIAL REGISTRATION: Clinical Trials.gov NCT03406052; https://www.clinicaltrials.gov/ct2/show/NCT03406052.

Predictors of remission after repetitive transcranial magnetic stimulation for the treatment of late-life depression.

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment in patients with depression, yet treatment response remains variable. While previous work has identified predictors of remission in younger adults, relatively little data exists in late-life depression (LLD). To address this gap, data from 164 participants with LLD from a randomized non-inferiority treatment trial comparing standard bilateral rTMS to bilateral theta burst stimulation (TBS) (ClinicalTrials.gov identifier: NCT02998580) were analyzed using binary logistic regression and conditional inference tree (CIT) modeling. Lower baseline depression symptom severity, fewer prior antidepressant treatment failures, and higher global cognition predicted remission following rTMS treatment. The CIT predicted a higher likelihood of achieving remission for patients with a total score of 19 or lower on the Montgomery-Åsberg Depression Rating Scale, 1 or fewer prior antidepressant treatment failures, and a total score of 23 or higher on the Montreal Cognitive Assessment. Our results indicate that older adults with lower severity of depression, fewer antidepressant treatment failures, and higher global cognition benefit more from current forms of rTMS. The results suggest that there is potentially higher value in using rTMS earlier in the treatment pathway for depression in older adults.

Shifting Mindsets: The Impact of a Patient Portal on Functioning and Recovery in a Mental Health Setting.

OBJECTIVE: This study aims to understand whether higher use of a patient portal can have an impact on mental health functioning and recovery. METHOD: A mixed methods approach was used for this study. In 2019-2021, patients with mental health diagnoses at outpatient clinics in an academic centre were invited to complete World Health Organization Disability Assessment Scale 12 (WHODAS-12) and Mental Health Recovery Measure surveys at baseline, 3 months, and 6 months after signing up for the portal. At the 3-month time point, patients were invited to a semistructured interview with a member of the team to contextualize the findings obtained from the surveys. Analytics data was also collected from the platform to understand usage patterns on the portal. RESULTS: Overall, 113 participants were included in the analysis. There was no significant change in mental health functioning and recovery scores over the 6-month period. However, suboptimal usage was observed as 46% of participants did not complete any tasks within the portal. Thirty-five participants had low use of the portal (1-9 interactions) and 18 participants had high usage (10+ interactions). There were also no differences in mental health functioning and recovery scores between low and high users of the portal. Qualitative interviews highlighted many opportunities where the portal can support overall functioning and mental health recovery. CONCLUSIONS: Collectively, this study suggests that higher use of a portal had no impact, either positive or negative, on mental health outcomes. While it may offer convenience and improved patient satisfaction, adequate support is needed to fully enable these opportunities for patient care. As the type of interaction with the portal was not specifically addressed, future work should focus on looking at ways to support patient engagement and portal usage throughout their care journey.

Outcomes among youth attending inpatient treatment for co-occurring disorders.

AIM: An emerging body of research is identifying effective outpatient integrated treatment approaches for youth with co-occurring psychiatric and substance use disorders, though few studies exist examining inpatient treatment. The current study aimed to address this gap by examining response to treatment during admission to, and in the year following discharge from, a specialized inpatient program for youth with co-occurring disorders. METHODS: A single-cohort longitudinal design examined change in adaptive functioning, mental health symptoms, and substance use frequency among N = 142 youth (69.1% female) aged 14-21 (M = 16.9, SD = 1.5) attending the program. Participants completed self-report measures at admission, discharge, and 1-, 6- and 12-months post-discharge. RESULTS: Analyses indicated significant improvements in adaptive functioning, internalizing and externalizing symptoms, and substance use frequency during admission. There was some loss of gains in adaptive functioning over the 12-months post-discharge. Improvements were maintained in internalizing symptoms and substance use frequency, and improvements in externalizing symptoms continued over the 12-months post-discharge. There was no significant interaction between change in functioning and internalizing symptoms at admission or type of substance use disorder diagnosis. There was a significant interaction with externalizing symptoms, such that those with clinically significant levels of externalizing symptoms at admission experienced greater improvement in functioning, though the groups ended treatment with comparable functioning scores. CONCLUSIONS: The results provide preliminary support for integrated treatment for co-occurring disorders delivered in an inpatient setting. However, the results also reflect the significant needs of youth with co-occurring disorders and the importance of ongoing care post-discharge from intensive treatment settings.

Landscape of Phase II Trials in Alzheimer's Disease.

BACKGROUND: Drug development in Alzheimer's disease (AD) over the past two decades has had high rates of failure. Novel trial designs, such as adaptive designs, have the potential to improve the efficiency of drug development in AD. OBJECTIVE: To evaluate the design characteristics, temporal trends, and differences in design between sponsor types in phase II trials of investigational agents in AD. METHODS: Phase I/II, II, and II/III trials for AD with drug or other biological interventions registered from December 1996 to December 2021 in ClinicalTrials.gov were included. Descriptive statistics were used to summarize trial characteristics. Linear, logistic, and multinomial regression models assessed temporal trends and differences between sponsor types in design characteristics. RESULTS: Of N = 474 trials identified, randomized parallel group design was the most common design (72%). Only 12 trials (2.5%) used an adaptive design; adaptive features included early stopping rules, model-based dose-finding, adaptive treatment arm selection, and response adaptive randomization. The use of non-randomized parallel-group and open-label single arm designs increased over time. No temporal trend in the use of adaptive design was identified. Trials sponsored by industry only were more likely to use a randomized parallel-group design and have a larger estimated sample size than trials with other sponsor types. CONCLUSION: Our systematic review showed that very few phase II trials in AD used an adaptive trial design. Innovation and implementation of novel trial designs in AD trials can accelerate the drug development process.

Associations over the COVID-19 pandemic period and the mental health and substance use of youth not in employment, education or training in Ontario, Canada: a longitudinal, cohort study.

BACKGROUND: The economic shutdown and school closures associated with the COVID-19 pandemic have negatively influenced many young people's educational and training opportunities, leading to an increase in youth not in education, employment, or training (NEET) globally and in Canada. NEET youth have a greater vulnerability to mental health and substance use problems, compared to their counterparts who are in school and/or employed. There is limited evidence on the association between COVID-19 and NEET youth. The objectives of this exploratory study included investigating: longitudinal associations between the COVID-19 pandemic and the mental health and substance use (MHSU) of NEET youth; and MHSU among subgroups of NEET and non-NEET youth. METHODS: 618 youth (14-28 years old) participated in this longitudinal, cohort study. Youth were recruited from four pre-existing studies at the Centre for Addiction and Mental Health. Data on MHSU were collected across 11 time points during the COVID-19 pandemic (April 2020-August 2022). MHSU were measured using the CoRonavIruS Health Impact Survey Youth Self-Report, the Global Appraisal of Individual Needs Short Screener, and the PTSD Checklist for DSM-5. Linear Mixed Models and Generalized Estimating Equations were used to analyze associations of NEET status and time on mental health and substance use. Exploratory analyses were conducted to investigate interactions between sociodemographic characteristics and NEET status and time. RESULTS: At baseline, NEET youth were significantly more likely to screen positive for an internalizing disorder compared to non-NEET youth (OR = 1.92; 95%CI=[1.26-2.91] p = 0.002). No significant differences were found between youth with, and without, NEET in MHSU symptoms across the study time frame. Youth who had significantly higher odds of screening positive for an internalizing disorder included younger youth (OR = 1.06, 95%CI=[1.00-1.11]); youth who identify as Trans, non-binary or gender diverse (OR = 8.33, 95%CI=[4.17-16.17]); and those living in urban areas (OR = 1.35, 95%CI=[1.03-1.76]), compared to their counterparts. Youth who identify as White had significantly higher odds of screening positive for substance use problems (OR = 2.38, 95%CI=[1.72-3.23]) compared to racialized youth. CONCLUSIONS: Our findings indicate that sociodemographic factors such as age, gender identity, ethnicity and area of residence impacted youth MHSU symptoms over the course of the study and during the pandemic. Overall, NEET status was not consistently associated with MHSU symptoms over and above these factors. The study contributes to evidence on MHSU symptoms of NEET youth.

Comparing analytical strategies for balancing site-level characteristics in stepped-wedge cluster randomized trials: a simulation study.

BACKGROUND: Stepped-wedge cluster randomized trials (SWCRTs) are a type of cluster-randomized trial in which clusters are randomized to cross-over to the active intervention sequentially at regular intervals during the study period. For SWCRTs, sequential imbalances of cluster-level characteristics across the random sequence of clusters may lead to biased estimation. Our study aims to examine the effects of balancing cluster-level characteristics in SWCRTs. METHODS: To quantify the level of cluster-level imbalance, a novel imbalance index was developed based on the Spearman correlation and rank regression of the cluster-level characteristic with the cross-over timepoints. A simulation study was conducted to assess the impact of sequential cluster-level imbalances across different scenarios varying the: number of sites (clusters), sample size, number of cross-over timepoints, site-level intra-cluster correlation coefficient (ICC), and effect sizes. SWCRTs assumed either an immediate "constant" treatment effect, or a gradual "learning" treatment effect which increases over time after crossing over to the active intervention. Key performance metrics included the relative root mean square error (RRMSE) and relative mean bias. RESULTS: Fully-balanced designs almost always had the highest efficiency, as measured by the RRMSE, regardless of the number of sites, ICC, effect size, or sample sizes at each time for SWCRTs with learning effect. A consistent decreasing trend of efficiency was observed by increasing RRMSE as imbalance increased. For example, for a 12-site study with 20 participants per site/timepoint and ICC of 0.10, between the most balanced and least balanced designs, the RRMSE efficiency loss ranged from 52.5% to 191.9%. In addition, the RRMSE was decreased for larger sample sizes, larger number of sites, smaller ICC, and larger effect sizes. The impact of pre-balancing diminished when there was no learning effect. CONCLUSION: The impact of pre-balancing on preventing efficiency loss was easily observed when there was a learning effect. This suggests benefit of pre-balancing with respect to impacting factors of treatment effects.

Efficacy of Telephone-Based Cognitive Behavioral Therapy for Weight Loss, Disordered Eating, and Psychological Distress After Bariatric Surgery: A Randomized Clinical Trial.

Importance: Weight regain after bariatric surgery is associated with recurrence of obesity-related medical comorbidities and deterioration in quality of life. Developing efficacious psychosocial interventions that target risk factors, prevent weight regain, and improve mental health is imperative. Objective: To determine the efficacy of a telephone-based cognitive behavioral therapy (tele-CBT) intervention at 1 year after bariatric surgery in improving weight loss, disordered eating, and psychological distress. Design, Setting, and Participants: This multisite randomized clinical trial was conducted at 3 hospital-based bariatric surgery programs, with recruitment between February 2018 and December 2021. Eligibility for participation was assessed among 314 adults at 1 year after bariatric surgery who were fluent in English and had access to a telephone and the internet. Patients with active suicidal ideation or poorly controlled severe psychiatric illness were excluded. Primary and secondary outcome measures were assessed at baseline (1 year after surgery), after the intervention (approximately 15 months after surgery), and at 3-month follow-up (approximately 18 months after surgery). Data were analyzed from January to February 2023. Interventions: The tele-CBT intervention consisted of 6 weekly 1-hour sessions and a seventh booster session 1 month later. The control group received standard postoperative bariatric care. Main Outcomes and Measures: The primary outcome was postoperative percentage total weight loss. Secondary outcomes were disordered eating (Binge Eating Scale [BES] and Emotional Eating Scale [EES]) and psychological distress (Patient Health Questionnaire-9 item scale [PHQ-9] and Generalized Anxiety Disorder-7 item scale [GAD-7]). The hypotheses and data-analytic plan were developed prior to data collection. Results: Among 306 patients 1 year after bariatric surgery (255 females [83.3%]; mean [SD] age, 47.55 [9.98] years), there were 152 patients in the tele-CBT group and 154 patients in the control group. The group by time interaction for percentage total weight loss was not significant (F1,160.61 = 2.09; P = .15). However, there were significant interactions for mean BES (F2,527.32 = 18.73; P < .001), EES total (F2,530.67 = 10.83; P < .001), PHQ-9 (F2,529.93 = 17.74; P < .001), and GAD-7 (F2,535.16 = 15.29; P < .001) scores between the tele-CBT group and control group across all times. Conclusions and Relevance: This study found that tele-CBT delivered at 1 year after surgery resulted in no change in short-term weight outcomes but improved disordered eating and psychological distress. The impact of these psychosocial improvements on longer-term weight outcomes is currently being examined as part of this longitudinal multisite randomized clinical trial. Trial Registration: ClinicalTrials.gov Identifier: NCT03315247.

Understanding the Role of Patient Portals in Fostering Interprofessional Collaboration Within Mental Health Care Settings: Mixed Methods Study.

BACKGROUND: Patient portals are web-based systems through which patients can access their personal health information and communicate with their clinicians. The integration of patient portals into mental health care settings has been evolving over the past decade, as cumulated research to date has highlighted the potential role of portals in facilitating positive health outcomes. However, it is currently unknown whether portal use can foster interprofessional collaboration between clinicians and patients or whether the portal is a tool to support an already established collaborative relationship. OBJECTIVE: This mixed methods study aimed to understand how the use of a patient portal within mental health settings can impact the level of interprofessional collaboration between clinicians and patients. METHODS: This study was conducted in a large mental health care organization in Ontario, Canada. A convergent mixed methods design was used, where the primary data collection methods included questionnaires and semistructured interviews with patients who had experience using a portal for their mental health care. For the quantitative strand, participants completed the Health Care Communication Questionnaire and the Self-Empowerment subscale of the Mental Health Recovery Measure at 3 time points (baseline, 3 months of use, and 6 months of use) to measure changes in scores over time. For the qualitative strand, semistructured interviews were conducted at the 3-month time point to assess the elements of interprofessional collaboration associated with the portal. RESULTS: For the quantitative strand, 113 participants completed the questionnaire. For the Health Care Communication Questionnaire scores, the raw means of the total scores at the 3 time points were as follows: baseline, 43.01 (SD 7.28); three months, 43.19 (SD 6.65); and 6 months, 42.74 (SD 6.84). In the univariate model with time as the only independent variable, the scores did not differ significantly across the 3 time points (P=.70). For the Mental Health Recovery Measure scores, the raw mean total scores at the 3 time points were as follows: baseline, 10.77 (SD 3.63); three months, 11.09 (SD 3.81); and 6 months, 11.10 (SD 3.33). In the univariate model with time as the only independent variable, the scores did not differ significantly across the 3 time points (P=.34). For the qualitative strand, 10 participants were interviewed and identified various elements of how interprofessional collaboration can be supplemented through the use of a patient portal, including improved team functioning, communication, and conflict resolution. CONCLUSIONS: Although the quantitative data produced nonsignificant findings in interprofessional collaboration scores over time, the patients' narrative accounts described how the portal can support various interprofessional collaboration concepts, such as communication, leadership, and conflict resolution. This provides useful information for clinicians to support the interprofessional relationship when using a portal within a mental health setting. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2018-025508.

Tolerability of ifosfamide-containing regimen in patients with high-risk renal and INI-1-deficient tumors.

BACKGROUND: Outcomes for children with high-risk renal (HRR) and INI-1-deficient (INI-) tumors are unacceptably poor. Concerns about excessive toxicity-as many are infants and/or undergo nephrectomy-have resulted in decreased chemotherapy dosing and omission of the nephrotoxic drug ifosfamide in collaborative group studies. As cause of death for children with these cancers remains overwhelmingly more from progressive disease rather than treatment toxicity, we examined the tolerability of an intensive ifosfamide-containing regimen. PROCEDURE: Retrospective review of children with HRR/INI- tumors treated at a single institution with vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide, carboplatin, etoposide (VDC-ICE) from 2006-2016. The primary outcome was regimen tolerability, including kidney injury and grade 3-5 nonhematologic toxicities. RESULTS: Fourteen patients with a median age of 1.7 years (range: 0.1-10.5) treated with VDC-ICE were identified. Diagnosis included malignant rhabdoid tumor (n = 9) (primary renal [n = 2]); diffuse anaplastic Wilms tumor (n = 3); clear cell sarcoma of the kidney (n = 1); and anaplastic chordoma (n = 1). All children with primary renal tumors (43%) underwent complete (n = 5) or partial nephrectomy (n = 1) before chemotherapy. Nine (64%) completed all intended cycles of chemotherapy; n = 5 (36%) did not due to disease progression. Unplanned hospitalizations occurred in 13 (93%) patients, most commonly for febrile neutropenia. No patient experienced severe organ toxicity, diminished renal function, treatment discontinuation due to toxicities, or treatment-related death. CONCLUSIONS: In children with HRR/INI- tumors, VDC-ICE chemotherapy was well-tolerated without excessive toxicities, even amongst young patients with solitary kidneys. Concerns about toxicity should not preclude an intensive ifosfamide-containing regimen from use in future trials in this population.

Derivation and validation of a risk classification tree for patients with synovial sarcoma.

BACKGROUND: Synovial sarcoma (SS) accounts for 8%-10% of all soft-tissue sarcomas. Clinical presentation and outcomes vary, yet discrete risk groups based on validated prognostic indices are not defined for the full spectrum of patients with SS. METHODS: We performed a retrospective cohort study using data from the SEER (surveillance, epidemiology, and end results program) database of SS patients who were <70 years of age at diagnosis. We constructed a recursive partitioning model of overall survival using a training cohort of 1063 patients with variables: Age at diagnosis, sex, race, ethnicity, primary site, tumor size, tumor grade, and stage. Based on this model, we grouped patients into three risk groups and estimated 5-year overall survival for each group. We then applied these groups to a test cohort (n = 1063). RESULTS: Our model identified three prognostic groups with significantly different overall survival: low risk (local/regional stage with either <21 years of age OR tumor <7.5 cm and female sex), intermediate-risk (local/regional stage, age ≥ 21 years with either male sex and tumor <7.5 cm OR any sex with appendicular anatomic location) and high risk (local/regional stage, age ≥ 21 years, tumor size ≥7.5 cm and non-appendicular location OR distant stage). Prognostic groups were applied to the test cohort, showing significantly different survival between groups (p < 0.0001). CONCLUSIONS: Our analysis yields an intuitive risk-classification tree with discrete groups, which may provide useful information for researchers, patients, and clinicians. Prospective validation of this model may inform efforts at risk-stratifying treatment.

Telephone-based cognitive behavioural therapy for patients with postoperative bariatric surgery to manage COVID-19 pandemic-related mental health issues and distress (TELE-BARICARE): a protocol for a randomised controlled trial.

INTRODUCTION: Bariatric surgery is currently the most effective treatment for obesity, and is performed yearly in over 8000 patients in Canada. Over 50% of those who live with obesity also have a history of mental health disorder. The COVID-19 pandemic has made it difficult for people living with obesity to manage their weight even after undergoing bariatric surgery, which combined with pandemic-related increases in mental health distress, has the potential to adversely impact obesity outcomes such as weight loss and quality of life. Reviews of virtual mental health interventions during COVID-19 have not identified any interventions that specifically address psychological distress or disordered eating in patients with obesity, including those who have had bariatric surgery. METHODS AND ANALYSIS: A randomised controlled trial will be conducted with 140 patients across four Ontario Bariatric Centres of Excellence to examine the efficacy of a telephone-based cognitive behavioural therapy intervention versus a control intervention (online COVID-19 self-help resources) in postoperative bariatric patients experiencing disordered eating and/or psychological distress. Patients will be randomised 1:1 to either group. Changes in the Binge Eating Scale and the Patient Health Questionnaire 9-Item Scale will be examined between groups across time (primary outcomes). Qualitative exit interviews will be conducted, and data will be used to inform future adaptations of the intervention to meet patients' diverse needs during and post-pandemic. ETHICS AND DISSEMINATION: This study has received ethics approvals from the following: Clinical Trials Ontario (3957) and the University Health Network Research Ethics Committee (22-5145), the Board of Record. All participants will provide written informed consent prior to enrolling in the study. Results will be made available to patients with bariatric surgery, the funders, the supporting organisations and other researchers via publication in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT05258578.

Canadian perspectives of digital mental health supports: Findings from a national survey conducted during the COVID-19 pandemic.

Objectives: The impact of the COVID-19 pandemic on population mental health has highlighted the potential for digital mental health to support the needs of those requiring care. This study sought to understand the digital mental health experiences and priorities of Canadians affected by mental health conditions (i.e. seekers, patients, and care partners). Methods: A national cross-sectional electronic survey of Canadians was administered through a market research firm's survey panel. Seekers, patients, and care partners were asked about their digital mental health experiences (e.g. uptake, barriers to access) and priorities. Survey responses were summarized using descriptive statistics. Results: Overall, 1003 participants completed the survey. 70.2% of participants routinely use digital mental health supports to support themselves or those they care for; however, only 28.6% of participants are satisfied with the available digital mental health supports. Most participants (73.3%) have encountered some barriers when accessing digital mental health supports. Awareness of digital mental health supports was a top barrier identified by participants. The top digital mental health priorities consisted of digital mental health curation, navigation, and a digital mental health passport. Conclusions: Most participants use digital mental health supports for themselves or others, however, many are unaware of digital mental health supports available. Efforts to improve navigating access to digital and in-person mental health services are seen as a top priority, highlighting the need to enable seekers, patients, and care partners to find the appropriate support and make decisions on how to best improve their mental health.

Planning for the Future of Digital Mental Health in Canada: Priorities of Canadians Affected by Mental Health Conditions.

Digital mental health tools have the potential to support people affected by mental health conditions. A pan-Canadian survey was conducted to understand the current and future digital health needs. The results show that Canadians prioritized tools that support them in navigating the physical and digital mental healthcare systems and that are integrated into their care.

Interventions for mental health, cognition, and psychological wellbeing in long COVID: a systematic review of registered trials.

BACKGROUND: Among patients diagnosed with COVID-19, a substantial proportion are experiencing ongoing symptoms for months after infection, known as 'long COVID'. Long COVID is associated with a wide range of physical and neuropsychological symptoms, including impacts on mental health, cognition, and psychological wellbeing. However, intervention research is only beginning to emerge. This systematic review synthesizes currently registered trials examining interventions for mental health, cognition, and psychological wellbeing in patients with long COVID. METHODS: Standard systematic review guidelines were followed. Trials registered in two large trial registries in 2020 to May 2022 were reviewed. Included studies were narratively synthesized by type of intervention and a risk-of-bias assessment was conducted. RESULTS: Forty-two registered trials were included, with a total target sample size of 5814 participants. These include 11 psychological interventions, five pharmacological and other medical interventions, and five evaluating herbal, nutritional, or natural supplement interventions. An additional nine trials are examining cognitive and neurorehabilitation interventions and 12 are examining physiotherapy or physical rehabilitation. Most trials are randomized, but many are feasibility trials; trials are evaluating a wide spectrum of outcomes. CONCLUSIONS: While there is a newly emerging body of research testing interventions for mental health, cognition, and psychological wellbeing in long COVID, the breadth and scope of the research remains limited. It is urgently incumbent on researchers to expand upon the intervention research currently under way, in order to generate high-quality evidence on a wide range of candidate interventions for diverse long COVID patient populations.

Impact of standardizing care for agitation in dementia using an integrated care pathway on an inpatient geriatric psychiatry unit.

OBJECTIVES: This study examined the effectiveness of an integrated care pathway (ICP), including a medication algorithm, to treat agitation associated with dementia. DESIGN: Analyses of data (both prospective and retrospective) collected during routine clinical care. SETTING: Geriatric Psychiatry Inpatient Unit. PARTICIPANTS: Patients with agitation associated with dementia (n = 28) who were treated as part of the implementation of the ICP and those who received treatment-as-usual (TAU) (n = 28) on the same inpatient unit before the implementation of the ICP. Two control groups of patients without dementia treated on the same unit contemporaneously to the TAU (n = 17) and ICP groups (n = 36) were included to account for any secular trends. INTERVENTION: ICP. MEASUREMENTS: Cohen Mansfield Agitation Inventory (CMAI), Neuropsychiatric Inventory Questionnaire (NPIQ), and assessment of motor symptoms were completed during the ICP implementation. Chart review was used to obtain length of inpatient stay and rates of psychotropic polypharmacy. RESULTS: Patients in the ICP group experienced a reduction in their scores on the CMAI and NPIQ and no changes in motor symptoms. Compared to the TAU group, the ICP group had a higher chance of an earlier discharge from hospital, a lower rate of psychotropic polypharmacy, and a lower chance of having a fall during hospital stay. In contrast, these outcomes did not differ between the two control groups. CONCLUSIONS: These preliminary results suggest that an ICP can be used effectively to treat agitation associated with dementia in inpatients. A larger randomized study is needed to confirm these results.

Two-stage subgroup-specific time-to-event (2S-Sub-TITE): An adaptive two-stage time-to-toxicity design for subgroup-specific dose finding in phase I oncology trials.

For phase I trials, the subgroup-specific time-to-event (Sub-TITE) design identifies the maximum tolerated dose (MTD) separately in 2+ heterogeneous patient subgroups. Sub-TITE allows borrowing strength and dynamic clustering across subgroups from the trial's start, but delaying the initiation of borrowing and clustering may improve trial accuracy. We propose the 2-stage Sub-TITE (2S-Sub-TITE) design in which the trial starts by estimating separate models per subgroup, and then initiates the Sub-TITE design at some pre-specified point of patient accrual. We evaluate the operating characteristics of the 2S-Sub-TITE design using simulations. Nine configurations of the 2S-Sub-TITE design (varying in timing of initiation of borrowing/clustering and prior probability of subgroup heterogeneity, p_hetero) and three control methods were compared across 1000 randomly-generated true toxicity probability scenarios. Effects of priors, sample size, escalation rules, target toxicity probability, accrual rate, and number of subgroups were evaluated. Metrics included: proportion of correct selection (PCS) of the true MTD, and average number of toxicities incurred. Among the 5 2S-Sub-TITE configurations (out of 9 total) with the highest PCS (45%) when the subgroup heterogeneity assumption is correct (all of which out-perform the control methods by 2%-6%), the configuration which enables borrowing and clustering allowance with p_hetero = 0.7 starting at 75% patient accrual best minimizes toxicities as well as losses in accuracy if the heterogeneity assumption is incorrect. For trials with high confidence in subgroup heterogeneity, the 2S-Sub-TITE configuration enabling borrowing/clustering with p_hetero = 0.7 starting at 75% patient accrual exhibits superior dose-finding accuracy compared to existing methods.

A Longitudinal Cohort Study of Youth Mental Health and Substance use Before and During the COVID-19 Pandemic in Ontario, Canada: An Exploratory Analysis.

BACKGROUND: Youth mental health appears to have been negatively impacted by the COVID-19 pandemic. The impact on substance use is less clear, as is the impact on subgroups of youth, including those with pre-existing mental health or substance use challenges. OBJECTIVE: This hypothesis-generating study examines the longitudinal evolution of youth mental health and substance use from before the COVID-19 pandemic to over one year into the pandemic among youth with pre-existing mental health or substance use challenges. METHOD: A total of 168 youth aged 14-24 participated. Participants provided sociodemographic data, as well as internalizing disorder, externalizing disorder, and substance use data prior to the pandemic's onset, then every two months between April 2020-2021. Linear mixed models and Generalized Estimating Equations were used to analyze the effect of time on mental health and substance use. Exploratory analyses were conducted to examine interactions with sociodemographic and clinical characteristics. RESULTS: There was no change in internalizing or externalizing disorder scores from prior to the pandemic to any point throughout the first year of the pandemic. Substance use scores during the pandemic declined compared to pre-pandemic scores. Exploratory analyses suggest that students appear to have experienced more mental health repercussions than non-students; other sociodemographic and clinical characteristics did not appear to be associated with mental health or substance use trajectories. CONCLUSIONS: While mental health remained stable and substance use declined from before the COVID-19 pandemic to during the pandemic among youth with pre-existing mental health challenges, some youth experienced greater challenges than others. Longitudinal monitoring among various population subgroups is crucial to identifying higher risk populations. This information is needed to provide empirical evidence to inform future research directions.

Investigating repetitive transcranial magnetic stimulation on cannabis use and cognition in people with schizophrenia.

Cannabis use disorder (CUD) occurs at high rates in schizophrenia, which negatively impacts its clinical prognosis. These patients have greater difficulty quitting cannabis which may reflect putative deficits in the dorsolateral prefrontal cortex (DLPFC), a potential target for treatment development. We examined the effects of active versus sham high-frequency (20-Hz) repetitive transcranial magnetic stimulation (rTMS) on cannabis use in outpatients with schizophrenia and CUD. Secondary outcomes included cannabis craving/withdrawal, psychiatric symptoms, cognition and tobacco use. Twenty-four outpatients with schizophrenia and CUD were enrolled in a preliminary double-blind, sham-controlled randomized trial. Nineteen participants were randomized to receive active (n = 9) or sham (n = 10) rTMS (20-Hz) applied bilaterally to the DLPFC 5x/week for 4 weeks. Cannabis use was monitored twice weekly. A cognitive battery was administered pre- and post-treatment. rTMS was safe and well-tolerated with high treatment retention (~90%). Contrast estimates suggested greater reduction in self-reported cannabis use (measured in grams/day) in the active versus sham group (Estimate = 0.33, p = 0.21; Cohen's d = 0.72), suggesting a clinically relevant effect of rTMS. A trend toward greater reduction in craving (Estimate = 3.92, p = 0.06), and significant reductions in PANSS positive (Estimate = 2.42, p = 0.02) and total (Estimate = 5.03, p = 0.02) symptom scores were found in the active versus sham group. Active rTMS also improved attention (Estimate = 6.58, p < 0.05), and suppressed increased tobacco use that was associated with cannabis reductions (Treatment x Time: p = 0.01). Our preliminary findings suggest that rTMS to the DLPFC is safe and potentially efficacious for treating CUD in schizophrenia.