Primary outcome reporting in clinical trials for older adults with depression.

BACKGROUND: Findings from randomised controlled trials (RCTs) are synthesised through meta-analyses, which inform evidence-based decision-making. When key details regarding trial outcomes are not fully reported, knowledge synthesis and uptake of findings into clinical practice are impeded. AIMS: Our study assessed reporting of primary outcomes in RCTs for older adults with major depressive disorder (MDD). METHOD: Trials published between 2011 and 2021, which assessed any intervention for adults aged ≥65 years with a MDD diagnosis, and that specified a single primary outcome were considered for inclusion in our study. Outcome reporting assessment was conducted independently and in duplicate with a 58-item checklist, used in developing the CONSORT-Outcomes statement, and information in each RCT was scored as 'fully reported', 'partially reported' or 'not reported', as applicable. RESULTS: Thirty-one of 49 RCTs reported one primary outcome and were included in our study. Most trials (71%) did not fully report over half of the 58 checklist items. Items pertaining to outcome analyses and interpretation were fully reported by 65% or more of trials. Items reported less frequently included: outcome measurement instrument properties (varied from 3 to 30%) and justification of the criteria used to define clinically meaningful change (23%). CONCLUSIONS: There is variability in how geriatric depression RCTs report primary outcomes, with omission of details regarding measurement, selection, justification and definition of clinically meaningful change. Outcome reporting deficiencies may hinder replicability and synthesis efforts that inform clinical guidelines and decision-making. The CONSORT-Outcomes guideline should be used when reporting geriatric depression RCTs.

Heterogeneity across outcomes reported in clinical trials for older adults with depression: a systematic survey.

OBJECTIVES: The objective of our study was to identify outcomes reported in trials for older adults with depression and describe outcome heterogeneity. STUDY DESIGN AND SETTING: We searched four databases to identify trials assessing any intervention for major depressive disorder among older adults published between 2011 and 2021. We grouped reported outcomes thematically and mapped them onto core outcome areas (physiological/clinical, life impact, resource use, adverse events, and death) and used descriptive analysis to summarize outcome heterogeneity. RESULTS: There were 434 total outcomes reported by 49 included trials, which were measured using 135 different outcome measurement instruments and grouped into 100 unique outcome terms. Most outcome terms mapped to the physiological/clinical core area (47%), followed by life impact (42%). More than half of all terms (53%) were reported by only a single study. Most trials (n = 31/49) reported a single, discernible primary outcome. The most commonly reported outcome "depressive symptom severity" was assessed by 36 studies using 19 different outcome measurement instruments. CONCLUSION: There is substantial heterogeneity in the outcomes and outcome measurement instruments used in geriatric depression trials. A standard set of outcomes and accompanying measurement tools is necessary to facilitate comparison and synthesis of trial findings.

Delirium and other neuropsychiatric manifestations of COVID-19 infection in people with preexisting psychiatric disorders: a systematic review.

BACKGROUND: Psychiatric disorders increase risk of neuropsychiatric disease and poor outcomes, yet little is known about the neuropsychiatric manifestations of COVID-19 in the psychiatric population. The primary objective is to synthesize neuropsychiatric outcomes of COVID-19 in people with preexisting psychiatric disorders. METHODS: Data were collected during an ongoing review of the impact of pandemics on people with existing psychiatric disorders. All study designs and gray literature were included. Medline, PsychInfo, CINAHL, EMBASE, and MedRx were searched from inception to September 1 2020. Risk of bias was assessed using a published tool that can accommodate all study types. Two independent authors screened the studies and extracted data. Data were narratively synthesized, as there were insufficient data to meta-analyze. Evidence was appraised according to GRADE. RESULTS: Four case reports were included, comprising 13 participants from three countries. Many large-sample, relevant papers were omitted for not reporting psychiatric history, despite reporting other comorbidities. Included participants (n = 13) were hospitalized with COVID-19 and appeared to meet criteria for delirium. Myoclonus, rigidity, and alogia were also reported. The most commonly reported preexisting psychiatric diagnoses were mood disorders, schizophrenia, and alcohol use disorder. CONCLUSIONS: People with preexisting psychiatric disorders may experience delirium, rigidity, myoclonus, and alogia during COVID-19 infection; although higher quality and longitudinal data are needed to better understand these phenomena. Relevant COVID-19 literature does not always report psychiatric history, despite heightened neuropsychiatric vulnerability within this population. TRIAL REGISTRATION:  PROSPERO (CRD42020179611).

Outcomes reported in randomised controlled trials of major depressive disorder in older adults: protocol for a methodological review.

INTRODUCTION: Major depressive disorder (MDD or depression) is prevalent among adults aged 65 years and older. The effectiveness and safety of interventions used to treat depression is often assessed through randomised controlled trials (RCTs). However, heterogeneity in the selection, measurement and reporting of outcomes in RCTs renders comparisons between trial results, interpretability and generalisability of findings challenging. There is presently no core outcome set (COS) for use in RCTs that assess interventions for older adults with MDD. We will conduct a methodological review of the literature for outcomes reported in trials for adults 65 years and older with depression to assess the heterogeneity of outcome measures. METHODS AND ANALYSIS: RCTs evaluating pharmacotherapy, psychotherapy, or any other treatment intervention for older adults with MDD published in the last 10 years will be located using electronic database searches (MEDLINE, Embase, PsycINFO and the Cochrane Central Register of Controlled Trials). Reviewers will conduct title and abstract screening, full-text screening and data extraction of trials eligible for inclusion independently and in duplicate. Outcomes will be synthesised and mapped to core outcome-domain frameworks. We will summarise characteristics associated with trials and outcomes. ETHICS AND DISSEMINATION: We hope that findings from our methodological review will reduce variability in outcome selection, measurement and reporting and facilitate the development of a COS for older adults with MDD. Our review will also inform evidence synthesis efforts in identifying the best treatment practices for this clinical population. Ethics approval is not required, as this study is a literature review. PROSPERO REGISTRATION NUMBER: CRD42021244753.

Problematic Opioid Use Among Older Adults: Epidemiology, Adverse Outcomes and Treatment Considerations.

With the aging population, an increasing number of older adults (> 65 years) will be affected by problematic opioid use and opioid use disorder (OUD), with both illicit and prescription opioids. Problematic opioid use is defined as the use of opioids resulting in social, medical or psychological consequences, whereas OUD is a form of problematic use that meets diagnostic criteria as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. Problematic use of opioids by older adults is associated with a number of pertinent adverse effects, including sedation, cognitive impairment, falls, fractures and constipation. Risk factors for problematic opioid use in this population include pain, comorbid medical illnesses, concurrent alcohol use disorder and depression. Treatment of OUD consists of acute detoxification and maintenance therapy. At this time, there have been no randomized controlled trials examining the effectiveness of pharmacological interventions for OUD in this population, with recommendations based on data from younger adults. Despite this, opioid agonist therapy (OAT) is recommended for both stages of treatment in older adults with OUD. Buprenorphine is recommended as a first line agent over methadone in the older adult population, due to a more favourable safety profile and relative accessibility. Use of methadone in this population is complicated by risk of QT interval prolongation and respiratory depression. Available observational data suggests that older adults respond well to OAT and age should not be a barrier to treatment. Further research is required to inform treatment decisions in this population.

Impact of COVID-19 and other pandemics and epidemics on people with pre-existing mental disorders: a systematic review protocol and suggestions for clinical care.

INTRODUCTION: The current COVID-19 pandemic has resulted in high rates of infection and death, as well as widespread social disruption and a reduction in access to healthcare services and support. There is growing concern over how the pandemic, as well as measures put in place to curb the pandemic, will impact people with mental disorders. We aim to study the effect of pandemics and epidemics on mental health outcomes for people with premorbid mental disorders. METHODS AND ANALYSIS: With our predefined search strategy, we will search five databases for studies reporting on mental health outcomes in people with pre-existing mental disorders during pandemic and epidemic settings. Search dates are planned as follows: 5 May 2020 and 23 July 2020. The following databases will be searched: MEDLINE/PubMed, CINAHL, PsycINFO, MedRxiv and EMBASE. Data will be screened and extracted in duplicate by two independent reviewers. Studies involving non-clinical populations or patients diagnosed with a mental disorder during a pandemic/epidemic will be excluded. We will include data collected from all pandemics and epidemics throughout history, including the present COVID-19 pandemic. If possible, study findings will be combined in meta-analyses, and subgroup analyses will be performed. We hope that this review will shed light on the impact of pandemics and epidemics on those with pre-existing mental disorders. Knowledge generated may inform future intervention studies as well as healthcare policies. Given the potential implications of the current pandemic measures (ie, disruption of healthcare services) on mental health, we will also compile a list of existing mental health resources. ETHICS AND DISSEMINATION: No ethical approval is required for this protocol and proposed systematic review as we will only use data from previously published papers that have themselves received ethics clearance and used proper informed consent procedures. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42020179611.

The use of cannabinoids for sleep: A critical review on clinical trials.

Cannabis and its pharmacologically active constituents, phytocannabinoids, have long been reported to have multiple medicinal benefits. One association often reported by users is sedation and subjective improvements in sleep. To further examine this association, we conducted a critical review of clinical studies examining the effects of cannabinoids on subjective and objective measures of sleep. PubMED, Web of Science, and Google Scholar were searched using terms and synonyms related to cannabinoids and sleep. Articles chosen included randomized controlled trials and open label studies. The Cochrane risk of bias tool was used to assess the quality of trials that compared cannabinoids with control interventions. The current literature focuses mostly on the use of tetrahydrocannabinol (THC) and/or cannabidiol (CBD) in the treatment of chronic health conditions such as multiple sclerosis, posttraumatic stress disorder (PTSD), and chronic pain. Sleep is often a secondary, rather than primary outcome in these studies. Many of the reviewed studies suggested that cannabinoids could improve sleep quality, decrease sleep disturbances, and decrease sleep onset latency. While many of the studies did show a positive effect on sleep, there are many limiting factors such as small sample sizes, examining sleep as a secondary outcome in the context of another illness, and relatively few studies using validated subjective or objective measurements. This review also identified several questions that should be addressed in future research. These questions include further elucidation of the dichotomy between the effects of THC and CBD, as well as identifying any long-term adverse effects of medicinal cannabinoid use. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Understanding and Managing Treatment Adherence in Schizophrenia.

Schizophrenia is a chronic, debilitating and costly illness. The course of illness is often exacerbated by relapses which are associated with negative outcomes including rehospitalisation. The most important risk factor associated with relapse is medication nonadherence. Medication nonadherence is not specific to schizophrenia and is an issue across all of medicine. The objective of this paper is to present a narrative review which synthesizes the rates and predictors of medication nonadherence, as well as associated interventions, across schizophrenia, first episode psychosis and general medicine. Given the breadth of these topics, this paper does not aim to present a complete review of the data but rather a concise synthesis of several lines of research in order to provide a general framework for approaching this important topic. Overall, this paper identifies that rates and risk factors of nonadherence in schizophrenia are similar to those reported in general medicine. Rates of adherence are estimated at 50% for both. Predictors of nonadherence were also quite similar between various illnesses, with lack of insight, poor family support and substance abuse often being highlighted. Well studied approaches of improving adherence include simplifying medication regimens, psychoeducation, engaging family support and use of long-acting injectable antipsychotics. Emerging interventions included text-message reminders, financial incentives and MyCite technology. Additionally, several evidence based interventions were identified in general medicine that may have applicability in schizophrenia and first episode psychosis. Lastly, avenues of future research were identified including the need to further characterize the dichotomy between adherence, partial adherence and nonadherence.

The rise and fall of the Mycobacterium tuberculosis genome.

When studied from the perspective of non-tuberculous mycobacteria (NTM) it is apparent that Mycobacterium tuberculosis has undergone a biphasic evolutionary process involving genome expansion (gene acquisition and duplication) and reductive evolution (deletions). This scheme can instruct descriptive and experimental studies that determine the importance of ancestral events (including horizontal gene transfer) in shaping the present-day pathogen. For example, heterologous complementation in an NTM can test the functional importance of M. tuberculosis-specific genetic insertions. An appreciation of both phases of M. tuberculosis evolution is expected to improve our fundamental understanding of its pathogenicity and facilitate the evaluation of novel diagnostics and vaccines.