Effects of Pycnogenol® in people with post-COVID-19 condition (PYCNOVID): study protocol for a single-center, placebo controlled, quadruple-blind, randomized trial.

BACKGROUND: A significant proportion of the global population has been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at some point since the onset of the pandemic. Although most individuals who develop coronavirus disease 2019 (COVID-19) recover without complications, about 6% have persistent symptoms, referred to as post-COVID-19 condition (PCC). Intervention studies investigating treatments that potentially alleviate PCC-related symptoms and thus aim to mitigate the global public health burden and healthcare costs linked to PCC are desperately needed. The PYCNOVID trial investigates the effects of Pycnogenol®, a French maritime pine bark extract with anti-inflammatory and antioxidative properties, versus placebo on patient-reported health status in people with PCC. METHODS: This is a single-center, placebo-controlled, quadruple blind, randomized trial. We aim to randomly assign 150 individuals with PCC (1:1 ratio) to receive either 200 mg Pycnogenol® or placebo daily for 12 weeks. Randomization is stratified for duration of PCC symptoms (≤ 6 months versus > 6 months) and presence of symptomatic chronic disease(s). The primary endpoint is perceived health status at 12 weeks (EuroQol-Visual Analogue Scale) adjusted for baseline values and stratification factors. Secondary endpoints include change in self-reported PCC symptoms, health-related quality of life, symptoms of depression and anxiety, cognitive function, functional exercise capacity, physical activity measured with accelerometry, and blood biomarkers for endothelial health, inflammation, coagulation, platelet function, and oxidative stress. Investigators, study participants, outcome assessors, and data analysts are blinded regarding the intervention assignment. Individuals with PCC were involved in the design of this study. DISCUSSION: This is the first trial to investigate the effects of Pycnogenol® versus placebo on patient-reported health status in people with PCC. Should the trial proof clinical effectiveness, Pycnogenol® may serve as a therapeutic approach to mitigate symptoms associated with PCC. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov. :NCT05890534, June 6, 2023.

Changes in mental and sexual health among MSM using HIV pre-exposure prophylaxis during the SARS-CoV-2 pandemic: longitudinal analysis of the SwissPrEPared cohort study.

BACKGROUND: Changes in mental and sexual health among men having sex with men (MSM) due to the SARS-CoV-2 pandemic remain unclear. METHODS: Design: Longitudinal analysis of an ongoing, multicentre, pre-exposure prophylaxis (PrEP) cohort (NCT03893188) in Switzerland. Participants: HIV-negative MSM aged ≥18 who completed at least one questionnaire before and one after the start of the SARS-CoV-2 pandemic. Outcomes: Primary: mental health, defined as anxiety and depression scores assessed by the Patient Health Questionnaire-4. Secondary: sexual behaviour, well-being, PrEP use and disruption of care. Outcomes were assessed over seven periods corresponding to different SARS-CoV-2 prevention measures in Switzerland. We performed pairwise comparisons between periods (Wilcoxon signed rank test). RESULTS: Data from 1,043 participants were included. Whilst anxiety scores remained stable over time, depression scores worsened in the second wave and the second lockdown period compared to pre-pandemic scores. This was confirmed by pairwise comparisons (pre-SARS-CoV-2/second wave and pre-SARS-CoV-2/second lockdown: p <0.001). Downward trends in sexual activity,sexualized substance use, and a switch from daily to "event-driven" PrEP were found. Disruption of care affected 42.6% (790/1856) of daily PrEP users' follow-up visits. CONCLUSION: In this longitudinal analysis of a PrEP cohort enrolling MSM, depression scores worsened in the second wave and the second lockdown compared to the pre-pandemic period.

Accelerated long-term forgetting in focal epilepsies with special consideration given to patients with diagnosed and suspected limbic encephalitis.

RATIONALE: Accelerated long-term forgetting (ALF) is a phenomenon found in late onset epilepsy and in transient epileptic amnesia (TEA). Here we evaluated ALF in patients with focal epilepsies and limbic encephalitis (LE) in particular. METHODS: ALF was assessed in 36 patients with focal epilepsy and 154 healthy subjects using an extended version of the Verbal Learning and Memory Test (VLMT), with free recall after 30 min and again after one week. From these patients, 89% had temporal lobe epilepsy; 42% left-lateralized; 39% right; 19% bilateral; 17% were diagnosed with hippocampal sclerosis; 64% displayed features indicating LE; 52% with amygdala pathology, and 61% were antibody positive. ALF was defined as either having unimpaired free recall after 30 min and impaired recall after a week (A) or as a loss in recall exceeding the absolute (B) and percentage loss (C) in the interval of the 30 min and one week recall seen in controls by more than one standard deviation. RESULTS: Repeated measures analysis revealed an association between LE and ALF. Depending on its definition (A, B, or C), ALF was evident in 31%, 42%, or 67% of the patients. Poor verbal memory and ALF (C) were prominent in left-lateralized epilepsies. ALF (A) appeared more frequently in auto-antibody negative patients with LE, ALF (B) less frequently with hippocampal sclerosis. Seizures during the interval did not explain ALF. CONCLUSION: Depending on its definition, ALF is seen in patients with normal or impaired memory at ½ h. ALF seems related to LE but might as well be the first sign of memory impairment in patients with milder epilepsies and not yet definite structural temporal lobe pathology. Longitudinal assessment would be essential for discerning when ALF becomes evident, whether conditions exist in which ALF precedes short-term forgetting, and whether ALF responds to treatment.