Real-world serological responses to extended-interval and heterologous COVID-19 mRNA vaccination in frail, older people (UNCoVER): an interim report from a prospective observational cohort study.

BACKGROUND: The use of COVID-19 vaccines has been prioritised to protect the most vulnerable-notably, older people. Because of fluctuations in vaccine availability, strategies such as delayed second dose and heterologous prime-boost have been used. However, the effectiveness of these strategies in frail, older people are unknown. We aimed to assess the antigenicity of mRNA-based COVID-19 vaccines in frail, older people in a real-world setting, with a rationed interval dosing of 16 weeks between the prime and boost doses. METHODS: This prospective observational cohort study was done across 12 long-term care facilities of the Montréal Centre-Sud - Integrated University Health and Social Services Centre in Montréal, Québec, Canada. Under a rationing strategy mandated by the provincial government, adults aged 65 years and older residing in long-term care facilities in Québec, Canada, with or without previously documented SARS-CoV-2 infection, were administered homologous or heterologous mRNA vaccines, with an extended 16-week interval between doses. All older residents in participating long-term care facilities who received two vaccine doses were eligible for inclusion in this study. Participants were enrolled from Dec 31, 2020, to Feb 16, 2021, and data were collected up to June 9, 2021. Clinical data and blood samples were serially collected from participants at the following timepoints: at baseline, before the first dose; 4 weeks after the first dose; 6-10 weeks after the first dose; 16 weeks after the first dose, up to 2 days before administration of the second dose; and 4 weeks after the second dose. Sera were tested for SARS-CoV-2-specific IgG antibodies (to the trimeric spike protein, the receptor-binding domain [RBD] of the spike protein, and the nucleocapsid protein) by automated chemiluminescent ELISA. Two cohorts were used in this study: a discovery cohort, for which blood samples were collected before administration of the first vaccine dose and longitudinally thereafter; and a confirmatory cohort, for which blood samples were only collected from 4 weeks after the prime dose. Analyses were done in the discovery cohort, with validation in the confirmatory cohort, when applicable. FINDINGS: The total study sample consisted of 185 participants. 65 participants received two doses of mRNA-1273 (Spikevax; Moderna), 36 received two doses of BNT162b2 (Comirnaty; Pfizer-BioNTech), and 84 received mRNA-1273 followed by BNT162b2. In the discovery cohort, after a significant increase in anti-RBD and anti-spike IgG concentrations 4 weeks after the prime dose (from 4·86 log binding antibody units [BAU]/mL to 8·53 log BAU/mL for anti-RBD IgG and from 5·21 log BAU/mL to 8·05 log BAU/mL for anti-spike IgG), there was a significant decline in anti-RBD and anti-spike IgG concentrations until the boost dose (7·10 log BAU/mL for anti-RBD IgG and 7·60 log BAU/mL for anti-spike IgG), followed by an increase 4 weeks later for both vaccines (9·58 log BAU/mL for anti-RBD IgG and 9·23 log BAU/mL for anti-spike IgG). SARS-CoV-2-naive individuals showed lower antibody responses than previously infected individuals at all timepoints tested up to 16 weeks after the prime dose, but achieved similar antibody responses to previously infected participants by 4 weeks after the second dose. Individuals primed with the BNT162b2 vaccine showed a larger decrease in mean anti-RBD and anti-spike IgG concentrations with a 16-week interval between doses (from 8·12 log BAU/mL to 4·25 log BAU/mL for anti-RBD IgG responses and from 8·18 log BAU/mL to 6·66 log BAU/mL for anti-spike IgG responses) than did those who received the mRNA-1273 vaccine (two doses of mRNA-1273: from 8·06 log BAU/mL to 7·49 log BAU/mL for anti-RBD IgG responses and from 6·82 log BAU/mL to 7·56 log BAU/mL for anti-spike IgG responses; mRNA-1273 followed by BNT162b2: from 8·83 log BAU/mL to 7·95 log BAU/mL for anti-RBD IgG responses and from 8·50 log BAU/mL to 7·97 log BAU/mL for anti-spike IgG responses). No differences in antibody responses 4 weeks after the second dose were noted between the two vaccines, in either homologous or heterologous combinations. INTERPRETATION: Interim results of this ongoing longitudinal study show that among frail, older people, previous SARS-CoV-2 infection and the type of mRNA vaccine influenced antibody responses when used with a 16-week interval between doses. In these cohorts of frail, older individuals with a similar age and comorbidity distribution, we found that serological responses were similar and clinically equivalent between the discovery and confirmatory cohorts. Homologous and heterologous use of mRNA vaccines was not associated with significant differences in antibody responses 4 weeks following the second dose, supporting their interchangeability. FUNDING: Public Health Agency of Canada, Vaccine Surveillance Reference Group; and the COVID-19 Immunity Task Force. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Treatment of pseudobulbar affect in a mixed neurodegenerative disorder with compounded quinidine capsules and dextromethorphan cough syrup.

An elderly woman admitted in our geriatric inpatient unit suffered from disturbing outbursts of crying and, less frequently, episodes of laughing. The patient was diagnosed with pseudobulbar affect related to a mixed neurodegenerative disorder. This condition is often underdiagnosed and undertreated, despite being relatively frequent in patients with neurodegenerative disorders. This case report describes the treatment of pseudobulbar affect in this patient. The only available treatment in Canada for this condition, antidepressants, was not effective for our patient. Dextromethorphan/quinidine is a good accepted alternative, but the combination is not marketed in Canada. To manage this problem, we used compounded quinidine capsules and dextromethorphan cough syrup. The crying of our patient improved significantly and rapidly after the initiation of this treatment. This case will help professionals to review their central role in treating this complex and disabling condition.

Social support and sleep quality in older benzodiazepine users.

Objective: Benzodiazepines (BZD) are often prescribed to address sleep difficulties but many BZD users report a poor quality of sleep. Although social support was found to be associated with quality of sleep in a recent meta-analysis, this relationship was never studied in older BZD users. This study thus aims to examine how social support is associated with quality of sleep in older BZD users.Method: Seventy-two older adults (age 60-85) using BZD were recruited. Data was collected during the pre-test of the ''PASSE-60+; Support program for a successful withdrawal, NCT02281175'' study. Quality of sleep was measured using the Pittsburgh Sleep Quality Index (PSQI), while social support was evaluated with the Social Support Questionnaire (SSQ-6).Results: When examining the various dimensions of self-reported sleep quality as a whole, we found no significant association with social support, while controlling for daily BZD dose, anxiety and depression. However, we found a significant association between self-reported diurnal dysfunctions (e.g., daytime sleepiness) and satisfaction with social support.Conclusion: Although the results of our study should be replicated with larger samples, they might indicate that social support is not a significant factor influencing sleep quality in older chronic BZD users. Our results could differ from those found in other populations because of the changes in sleep quality associated with long term BZD use. Longitudinal studies should analyse the relationship between diurnal dysfunctions and satisfaction with social support, to examine if social support could help older adults alleviate their diurnal dysfunctions and eventually facilitate BZD tapering.

Psychological predictors of benzodiazepine discontinuation among older adults: Results from the PASSE 60.

BACKGROUND: Long-term benzodiazepine (BZD) use among seniors is mostly inappropriate and associated with adverse health outcomes. To prevent these consequences, withdrawal is crucial, yet knowledge is limited about what predicts BZD discontinuation. Until now, most studies have focused on sociodemographic and BZD intake factors as predictors while neglecting psychological factors. This research addresses this issue by studying how the intensity of depressive symptoms, social support satisfaction, self-perceived competence in the ability to withdraw, and overall quality of sleep predict discontinuation in long-term older consumers. METHOD: Seventy-three participants aged 60 years and older were enrolled in this study. There were four time measures: before discontinuation (T1), after (T2), 3 months after (T3), and 12 months after (T4). Data were collected in the "Programme d'Aide du Succès au SEvrage" (PASSE-60+) study. RESULTS: Social support satisfaction predicted discontinuation at T2 and T4. Self-perceived competence in the ability to withdraw and depressive symptoms predicted discontinuation at T4. This later prediction was counterintuitive; higher depressive symptoms at T1 were linked with higher discontinuation success. BZD intake factors (length of use and dose) were good predictors for short term discontinuation. Psychological factors were moderate predictors for short term and good predictors for long term discontinuation. CONCLUSION: Psychological factors are good predictors of discontinuation and are better predictors than BZD intake factors of long-term discontinuation. Discontinuation programs should focus on social support and self-perceived competence to improve their efficacy. Further studies are needed to acquire a more complete picture of the psychological predictors of discontinuation success. ClinicalTrials.gov Identifier: NCT02281175.

The Association between Generalized Anxiety Disorder, Subthreshold Anxiety Symptoms and Fear of Falling among Older Adults: Preliminary Results from a Pilot Study.

OBJECTIVE: A relationship between generalized anxiety disorder (GAD) and fear of falling (FOF) has long been proposed but never specifically studied. This study aimed at analyzing the relationship between FOF and GAD or anxiety symptoms, while controlling for major depressive episodes (MDE), depressive symptoms, fall risk, and sociodemographic variables. METHODS: Twenty-five older adults participated in this pilot study. Assessments included the following: Anxiety Disorder Interview Schedule, Geriatric Anxiety Inventory, Geriatric Depression Scale, Falls-Efficacy Scale-International. A multidisciplinary team evaluated fall risk. RESULTS: FOF was significantly correlated with GAD, MDE, anxiety and depressive symptoms, and fall risk, but not with sociodemographic variables. Multiple regression analyses indicated that GAD and anxiety symptoms were significantly and independently associated with FOF. CONCLUSION: Although the results of this pilot study should be replicated with larger samples, they suggest that FOF is associated with GAD and anxiety symptoms even when considering physical factors that increase the risk of falling. CLINICAL IMPLICATIONS: Treatment of FOF in patients with GAD may present a particular challenge because of the central role of intolerance of uncertainty, which may prevent patients from regaining confidence despite the reduction of fall risk. Clinicians should screen for GAD and anxiety symptoms in patients with FOF to improve detection and treatment.