A Randomized, Double-Blind, Placebo-Controlled Trial of a Polyphenol Botanical Blend on Sleep and Daytime Functioning

Despite the high prevalence of subclinical sleep disturbances, existing treatments are either potent prescription medications or over-the-counter supplements with minimal scientific support and numerous side effects. However, preliminary evidence shows that polyphenols such as rosmarinic acid and epigallocatechin gallate can support healthy sleep without significant side effects. Therefore, the present study examined whether a polyphenol botanical blend (PBB) could improve sleep and/or daytime functioning in individuals with subclinical sleep disturbances. A total of 89 individuals completed a double-blind, randomized trial of daily treatment with PBB (n = 43) or placebo (n = 46) 30 min before bed for 30 days. Participants were monitored for changes in sleep (by sleep diary and an activity tracker), mood, and neurocognitive functioning. After 30 days, PBB improved diary sleep quality (p = 0.008) and reduced insomnia severity (p = 0.044) when compared to placebo. No other changes in sleep outcomes were observed. Additionally, PBB did not impair neurocognitive functioning, and some improvement was noted in vigilant attention, working memory, and risk assessment. Among individuals with subclinical sleep disturbances, PBB improved sleep quality, insomnia severity, and neurocognitive functioning over placebo. These findings indicate that polyphenol compounds may be useful for improving certain aspects of sleep without compromising neurocognitive functioning

Long-acting injectable Cabotegravir + Rilpivirine for HIV maintenance therapy: Week 48 pooled analysis of phase 3 ATLAS and FLAIR trials

BACKGROUND: Long-acting (LA) injectable regimens are a potential therapeutic option in people living with HIV-1. SETTING: ATLAS (NCT02951052) and FLAIR (NCT02938520) were 2 randomized, open-label, multicenter, multinational phase 3 studies. METHODS: Adult participants with virologic suppression (plasma HIV-1 RNA <50 copies/mL) were randomized (1:1) to continue with their current antiretroviral regimen (CAR) or switch to the long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). In the LA arm, participants initially received oral CAB + RPV once-daily for 4 weeks to assess individual safety and tolerability, before starting monthly injectable therapy. The primary endpoint of this combined analysis was antiviral efficacy at week 48 (FDA Snapshot algorithm: noninferiority margin of 4% for HIV-1 RNA ≥50 copies/mL). Safety, tolerability, and confirmed virologic failure (2 consecutive plasma HIV-1 RNA ≥200 copies/mL) were secondary endpoints. RESULTS: The pooled intention-to-treat exposed population included 591 participants in each arm [28% women (sex at birth), 19% aged ≥50 years]. Noninferiority criteria at week 48 were met for the primary (HIV-1 RNA ≥50 copies/mL) and key secondary (HIV-1 RNA <50 copies/mL) efficacy endpoints. Seven individuals in each arm (1.2%) developed confirmed virologic failure; 6/7 (LA) and 3/7 (CAR) had resistance-associated mutations. Most LA recipients (83%) experienced injection site reactions, which decreased in incidence over time. Injection site reactions led to the withdrawal of 6 (1%) participants. The serious adverse event rate was 4% in each arm. CONCLUSION: This combined analysis demonstrates monthly injections of CAB + RPV LA were noninferior to daily oral CAR for maintaining HIV-1 suppression

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Functional and quality of life outcomes of localised prostate cancer treatments (prostate testing for cancer and treatment [ProtecT] study)

Objective To investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision-making. Patients and Methods Men aged 50–69 years diagnosed with localised prostate cancer by prostate-specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) with concurrent androgen-deprivation therapy (ADT) and 77 low-dose-rate brachytherapy (BT, not a randomised treatment). Patient-reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores. Results Treatment-received analyses revealed different impacts of treatments over 6 years. Men remaining on AM experienced gradual declines in sexual and urinary function with age (e.g., increases in erectile dysfunction from 35% of men at baseline to 53% at 6 years and nocturia similarly from 20% to 38%). Radical treatment impacts were immediate and continued over 6 years. After RP, 95% of men reported erectile dysfunction persisting for 85% at 6 years, and after EBRT this was reported by 69% and 74%, respectively (P < 0.001 compared with AM). After RP, 36% of men reported urinary leakage requiring at least 1 pad/day, persisting for 20% at 6 years, compared with no change in men receiving EBRT or AM (P < 0.001). Worse bowel function and bother (e.g., bloody stools 6% at 6 years and faecal incontinence 10%) was experienced by men after EBRT than after RP or AM (P < 0.001) with lesser effects after BT. No treatment affected mental or physical QoL. Conclusion Treatment decision-making for localised prostate cancer can be informed by these 6-year functional and QoL outcomes

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

Nightmare content during the COVID‐19 pandemic: Influence of COVID‐related stress and sleep disruption in the United States

International audienceNightmares are often associated with psychiatric disorders and acute stress. This study explores how the COVID-19 pandemic may have influenced the content of nightmares. A sample of N = 419 US adults completed online surveys about sleep and COVID-19 experiences. Participants were asked about the degree to which they agreed with statements linking greater general stress, worse overall sleep and more middle-of-the-night insomnia with the COVID-19 pandemic. They were also asked if, during the pandemic, they experienced nightmares related to various themes. Logistic regression analyses examined each nightmare content as outcome and increased stress, worse sleep and more middle-of-the-night insomnia as predictors, adjusted for age, sex and race/ethnicity. Those who reported greater general COVID-related stress were more likely to have nightmares about confinement, failure, helplessness, anxiety, war, separation, totalitarianism, sickness, death, COVID and an apocalypse. Those who reported worsened sleep were more likely to have nightmares about confinement, oppression, failure, helplessness, disaster, anxiety, evil forces, war, domestic abuse, separation, totalitarianism, sickness, death, COVID and an apocalypse. Those who reported worsened middle-of-the-night insomnia were more likely to have nightmares about confinement, oppression, failure, helplessness, disaster, anxiety, war, domestic abuse, separation, totalitarianism, sickness, death, COVID and an apocalypse. These results suggest that increased pandemic-related stress may induce negatively-toned dreams of specific themes. Future investigation might determine whether (and when) this symptom indicates an emotion regulation mechanism at play, or the failure of such a mechanism

0272 Decreased Risk of 2-Year Incidence of Alzheimer’s Disease Among Older Adults Who Report Sleep Symptoms

Abstract Introduction Those with dementia or Alzheimer’s Disease report an elevated amount of sleep difficulties compared to age-matched controls. Sleep-based interventions may be especially useful for this group, such as cognitive behavioral therapy for insomnia or pharmacological interventions. Therefore, it is important to expand the current understanding of the nature of sleep difficulties in those with Alzheimer’s Disease. Methods Data from the 2018 Health and Retirement Survey was collected from 17,146 older adults. Poisson regression analyses were used to explore the relationship between Alzheimer’s Disease as diagnosed by a doctor and sleep difficulties. Individuals who reported no Alzheimer’s Disease in the previous wave (N=16,751) were asked if they had since become diagnosed. N=101 individuals reported incident Alzheimer’s Disease in the 2-year gap between assessments. Sleep difficulties were assessed by asking participants if they had difficulties initiating or maintaining sleep, waking up too early, and how rested they felt upon awakening. All 4 of these symptoms were coded as “never,” “sometimes,” or “often.” Results Unexpectedly, there was a significant decreased risk of developing Alzheimer’s Disease among those who reported difficulties maintaining sleep (IRR=0.9962; 95%CI[0.9936,0.9988]; p=0.004), and early morning awakenings (IRR=0.9961; 95%CI[0.9938,0.9984]; p=0.001) “sometimes”. When the model was adjusted for sex, race, ethnicity, age, and depression, a similar finding of decreased risk for Alzheimer’s Disease for those who reported difficulties maintaining sleep (IRR=0.9953; 95%CI[0.9927,0.9980]; p<0.001), and early morning awakenings (IRR=0.9954; 95%CI[0.9930,0.9978]; p=0.001), “sometimes” were maintained. Conclusion Although previous studies have shown that poor sleep may lead to increased risk of Alzheimer’s and related dementias, the present study, which examined longitudinal data from a large, national sample of older adults, found that there was no association between frequent sleep disturbances and 2-year incidence of Alzheimer’s Disease, and a small association between more mild symptoms and decreased risk. It is possible that the 2-year observation window was insufficient to detect effects. Also, there is a risk of measurement error in collecting self-reported data on sleep and Alzheimer’s diagnoses. Support (If Any) The HRS (Health and Retirement Study) is sponsored by the National Institute on Aging (grant number NIA U01AG009740) and is conducted by the University of Michigan

Chronotype and social support among student athletes: impact on depressive symptoms

Previous studies have shown individuals with evening chronotype to have a greater likelihood for depression (self-reported and clinical ratings), especially in young adults. However, the mechanisms for this relationship remain unknown. Low levels of social support may be a plausible mechanism: young adults with evening chronotypes are awake when others are sleeping, which may lead to feelings of isolation or low support. This study examined links between chronotype, depression, and social support in relationship subtypes within a group of university student athletes. Data were obtained from 189 NCAA Division-I student athletes across all sports. Chronotype was assessed with the Circadian Energy Scale and ranged from −2 (definitely morning type) to +2 (definitely evening type). Depressive symptoms were assessed with Center for Epidemiological Studies Depression scale. Social support was assessed with the Multidimensional Scale of Perceived Social Support, which included subscales for Family, Friends, and Significant Other. A subscale for Team was created using the items from the Friends subscale (changing the word “friends” to “teammates”). Regression analyses adjusted for age, sex, and minority status. More evening chronotype was associated with higher reported depressive symptoms (p = .018), lower overall perceived social support (p = .001), and lower perceived social support specifically provided by family (p < .0001), friends (p < .0001), and teammates (p = .014). However, more evening chronotype was associated with higher depressive symptoms for higher, but not lower perceived social support from significant other. Moreover, chronotype-by-support interactions on depressive symptoms were observed; the statistical relationship between chronotype and depression was evident only in those with low (but not high) social support from friends and teammates. These data suggest that having a more evening chronotype may be associated with social isolation, and decreased opportunities for interactions with friends and teammates. This may contribute to the long-standing circadian association seen with depression in college student-athletes. Interventions aimed at increasing university support networks may reduce the impact of depression in students self-identifying with later chronotypes and sleep schedules. © 2021 Taylor & Francis Group, LLC.National Collegiate Athletic Association12 month embargo; published online: 26 May 2021This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]