Population impact of SARS-CoV-2 variants with enhanced transmissibility and/or partial immune escape.

SARS-CoV-2 variants of concern exhibit varying degrees of transmissibility and, in some cases, escape from acquired immunity. Much effort has been devoted to measuring these phenotypes, but understanding their impact on the course of the pandemic-especially that of immune escape-has remained a challenge. Here, we use a mathematical model to simulate the dynamics of wild-type and variant strains of SARS-CoV-2 in the context of vaccine rollout and nonpharmaceutical interventions. We show that variants with enhanced transmissibility frequently increase epidemic severity, whereas those with partial immune escape either fail to spread widely or primarily cause reinfections and breakthrough infections. However, when these phenotypes are combined, a variant can continue spreading even as immunity builds up in the population, limiting the impact of vaccination and exacerbating the epidemic. These findings help explain the trajectories of past and present SARS-CoV-2 variants and may inform variant assessment and response in the future.

Marizomib (Salinosporamide A) Promotes Apoptosis in A375 and G361 Melanoma Cancer Cells.

Malignant melanoma-a tumor originating from melanocytes-is characterized by dynamic growth and frequent metastases in the early stage of development. Current therapy methods are still insufficient, and there is a need to search for new ways of treating this malady. The induction of apoptosis-physiological cell death-by proteasome inhibitors is recognized as an effective method of non-invasive elimination of cancer cells. In our research, we wanted to check the potential of marizomib (MZB, salinosporamide A, NPI-0052)-an irreversible proteasome inhibitor derived from the marine actinomycete Salinispora tropica-to induce apoptosis in A375 and G361 malignant melanoma cells. We determined the cytotoxic activity of marizomib by performing an MTT test. Ethidium bromide and acridine orange staining demonstrated the disruption of membrane integrity in the examined cell lines. We confirmed the proapoptotic activity of marizomib by flow cytometry with the use of an FITC-Annexin V assay. A Western blot analysis presented an increase in the expression of proteins related to endoplasmic reticulum (ER) stress as well as markers of the apoptosis. The gathered findings suggest that marizomib induced the ER stress in the examined melanoma cancer cells and directed them towards the apoptosis pathway.

Impact of combination preventative interventions on hospitalization and death under the pandemic of SARS-CoV-2 Omicron variant in China.

With a large population most susceptible to Omicron and emerging SARS-CoV-2 variants, China faces uncertain scenarios if reopening its border. Thus, we aimed to predict the impact of combination preventative interventions on hospitalization and death. An age-stratified susceptible-infectious-quarantined-hospitalized-removed-susceptible (SIQHRS) model based on the new guidelines of COVID-19 diagnosis and treatment (the ninth edition) was constructed to simulate the transmission dynamics of Omicron within 365 days. At baseline, we assumed no interventions other than 60% booster vaccination in individuals aged ≤60 years and 80% in individuals aged >60 years, quarantine and hospitalization. Oral antiviral medications for COVID-19 and nonpharmaceutical interventions (NPIs) such as social distancing and antigen self-testing were considered in subsequent scenarios. Sensitivity analyses were conducted to reflect different levels of interventions. A total of 0.73 billion cumulative quarantines (95% CI 0.53-0.83), 33.59 million hospitalizations (22.41-39.31), and 0.62 million deaths (0.40-0.75) are expected in 365 days. The case fatality rate with pneumonia symptoms (moderate, severe and critical illness) is expected to be 1.83% (1.68-1.99%) and the infected fatality rate is 0.38‰ (0.33-0.4‰). The highest existing hospitalization and ICU occupations are 3.11 (0.30-3.85) and 20.33 (2.01-25.20) times of capacity, respectively. Sensitivity analysis showed that interventions can be adjusted to meet certain conditions to reduce the total number of infections and deaths. In conclusion, after sufficient respiratory and ICU beds are prepared and the relaxed NPIs are in place, the SARS-CoV-2 Omicron variant would not seriously impact the health system.

Frequency and imaging correlates of neuropsychiatric symptoms in Progressive Supranuclear Palsy.

Neuropsychiatric symptoms are intrinsic to Progressive Supranuclear Palsy (PSP) and a spoonful of studies investigated their imaging correlates. Describe (I) the frequency and severity of neuropsychiatric symptoms in PSP and (II) their structural imaging correlates. Twenty-six PSP patients underwent Neuropsychiatric Inventory (NPI) and brain 3D T1-weighted MRI. Spearman's rho with Bonferroni correction was used to investigate correlations between NPI scores and volumes of gray matter regions. More than 80% of patients presented at least one behavioral symptom of any severity. The most frequent and severe were depression/dysphoria, apathy, and irritability/lability. Significant relationships were found between the severity of irritability and right pars opercularis volume (p < 0.001) as well as between the frequency of agitation/aggression and left lateral occipital volume (p < 0.001). Depression, apathy, and irritability are the most common neuropsychiatric symptoms in PSP. Moreover, we found a relationship between specific positive symptoms as irritability and agitation/aggression and greater volume of the right pars opercularis cortex and lower volume of the left occipital cortex, respectively, which deserve further investigations.

Effects of contact tracing and nucleic acid testing on the COVID-19 outbreak in Zunyi, China: data-driven study using a branching process model.

BACKGROUND: During October 2021, China experienced localized outbreaks of COVID-19 in many cities. We analyzed the small local outbreak in Zunyi (Guizhou Province), a major city in southwestern China, and modeled the effects of different interventions on this outbreak. METHODS: Data on infections and contacts, provided by the Health Commission of Guizhou Province, were used to analyze the epidemiological characteristics of the outbreak and calculate the effectiveness of vaccination. A branching process model was used to simulate the outbreak. This model considered the time interval from exposure of the initial case to confirmation, the number of potential infections caused by the initial case, and the effects of the different interventions. RESULTS: From 18 to 25 October 2021, there were 12 patients with COVID-19 in Zunyi. Overall, the average age was 67.17 years-old, 8 patients were females, and 1 patient had an asymptomatic infection. The effectiveness of two-dose inactivated vaccine against SARS-CoV-2 infection was 16.7% (95% CI: 2.8% to 99.7%). The initial case was infected on 11 or 12 October 2021, 6.40 (95% CI: 6.37, 6.42; IQR: 4.92, 7.63) days before confirmation while the travelling in Lanzhou (Gansu Province). There were 10.07 (95% CI: 10.04, 10.09; IQR: 7.86, 11.93) potential secondary cases. When the effective vaccine coverage reached 60%, the probability of cumulative cases exceeding 20 was less than 8.77%, even if contact tracing was relaxed or eliminated. However, if the probability of tracing contacts decreased, earlier initiation of nucleic acid testing was necessary to control the outbreak. CONCLUSIONS: The COVID-19 outbreak in Zunyi was controlled quickly due to moderately effective vaccine coverage and rapid contact tracing. For controlling localized outbreaks, vaccination and contact tracing seemed to be more effective than massive nucleic acid testing in the initial phase of transmission. However, if there is low effective vaccine coverage or insufficient contact tracing, nucleic acid testing should start earlier.

Lessons drawn from Shanghai for controlling highly transmissible SARS-CoV-2 variants: insights from a modelling study.

BACKGROUND: The continuous emergence of novel SARS-CoV-2 variants with markedly increased transmissibility presents major challenges to the zero-COVID policy in China. It is critical to adjust aspects of the policy about non-pharmaceutical interventions (NPIs) by searching for and implementing more effective ways. We use a mathematical model to mimic the epidemic pattern of the Omicron variant in Shanghai to quantitatively show the control challenges and investigate the feasibility of different control patterns in avoiding other epidemic waves. METHODS: We initially construct a dynamic model with a core step-by-step release strategy to reveal its role in controlling the spread of COVID-19, including the city-based pattern and the district-based pattern. We used the least squares method and real reported case data to fit the model for Shanghai and its 16 districts, respectively. Optimal control theory was utilized to explore the quantitative and optimal solutions of the time-varying control strength (i.e., contact rate) to suppress the highly transmissible SARS-CoV-2 variants. RESULTS: The necessary period for reaching the zero-COVID goal can be nearly 4 months, and the final epidemic size was 629,625 (95%CI: [608,049, 651,201]). By adopting the city-based pattern, 7 out of 16 strategies released the NPIs more or earlier than the baseline and ensured a zero-resurgence risk at the average cost of 10 to 129 more cases in June. By adopting the district-based pattern, a regional linked release can allow resumption of social activity to ~ 100% in the boundary-region group about 14 days earlier and allow people to flow between different districts without causing infection resurgence. Optimal solutions of the contact rate were obtained with various testing intensities, and higher diagnosis rate correlated with higher optimal contact rate while the number of daily reported cases remained almost unchanged. CONCLUSIONS: Shanghai could have been bolder and more flexible in unleashing social activity than they did. The boundary-region group should be relaxed earlier and more attention should be paid to the centre-region group. With a more intensive testing strategy, people could return to normal life as much as possible but still ensure the epidemic was maintained at a relatively low level.

A model for predicting ncRNA-protein interactions based on graph neural networks and community detection.

Non-coding RNA (ncRNA) s play an considerable role in the current biological sciences, such as gene transcription, gene expression, etc. Exploring the ncRNA-protein interactions(NPI) is of great significance, while some experimental techniques are very expensive in terms of time consumption and labor cost. This has promoted the birth of some computational algorithms related to traditional statistics and artificial intelligence. However, these algorithms usually require the sequence or structural feature vector of the molecule. Although graph neural network (GNN) s has been widely used in recent academic and industrial researches, its potential remains unexplored in the field of detecting NPI. Hence, we present a novel GNN-based model to detect NPI in this paper, where the detecting problem of NPI is transformed into the graph link prediction problem. Specifically, the proposed method utilizes two groups of labels to distinguish two different types of nodes: ncRNA and protein, which alleviates the problem of over-coupling in graph network. Subsequently, ncRNA and protein embedding is initially optimized based on the cluster ownership relationship of nodes in the graph. Moreover, the model applies a self-attention mechanism to preserve the graph topology to reduce information loss during pooling. The experimental results indicate that the proposed model indeed has superior performance.

Neuropsychiatric features in a multi-ethnic population with Alzheimer disease and mild cognitive impairment.

BACKGROUND: Alzheimer disease (AD) is more prevalent in African American (AA) and Hispanic White (HIW) compared to Non-Hispanic White (NHW) individuals. Similarly, neuropsychiatric symptoms (NPS) vary by population in AD. This is likely the result of both sociocultural and genetic ancestral differences. However, the impact of these NPS on AD in different groups is not well understood. METHODS: Self-declared AA, HIW, and NHW individuals were ascertained as part of ongoing AD genetics studies. Participants who scored higher than 0.5 on the Clinical Dementia Rating (CDR) Scale (CDR) were included. Group similarities and differences on Neuropsychiatric Inventory Questionnaire (NPI-Q) outcomes (NPI-Q total score, NPI-Q items) were evaluated using univariate ANOVAs and post hoc comparisons after controlling for sex and CDR stage. RESULTS: Our sample consisted of 498 participants (26% AA; 30% HIW; 44% NHW). Overall, NPI-Q total scores differed significantly between our groups, with HIW having the highest NPI-Q total scores, and by AD stage as measured by CDR. We found no significant difference in NPI-Q total score by sex. There were six NPI-Q items with comparable prevalence in all groups and six items that significantly differed between the groups (Anxiety, Apathy, Depression, Disinhibition, Elation, and Irritability). Further, within the HIW group, differences were found between Puerto Rican and Cuban American Hispanics across several NPI-Q items. Finally, Six NPI-Q items were more prevalent in the later stages of AD including Agitation, Appetite, Hallucinations, Irritability, Motor Disturbance, and Nighttime Behavior. CONCLUSIONS: We identified differences in NPS among HIW, AA, and NHW individuals. Most striking was the high burden of NPS in HIW, particularly for mood and anxiety symptoms. We suggest that NPS differences may represent the impact of sociocultural influences on symptom presentation as well as potential genetic factors rooted in ancestral background. Given the complex relationship between AD and NPS it is crucial to discern the presence of NPS to ensure appropriate interventions.

Unintended consequences of implementing non-pharmaceutical interventions for the COVID-19 response in Africa: experiences from DRC, Nigeria, Senegal, and Uganda.

INTRODUCTION: The coronavirus (COVID 19) pandemic is one of the most terrifying disasters of the twenty-first century. The non-pharmaceutical interventions (NPIs) implemented to control the spread of the disease had numerous positive consequences. However, there were also unintended consequences-positively or negatively related to the nature of the interventions, the target, the level and duration of implementation. This article describes the unintended economic, Psychosocial and environmental consequences of NPIs in four African countries. METHODS: We conducted a mixed-methods study in the Democratic Republic of Congo (DRC), Nigeria, Senegal and Uganda. A comprehensive conceptual framework, supported by a clear theory of change was adopted to encompass both systemic and non-systemic interventions. The data collection approaches included: (i) review of literature; (ii) analysis of secondary data for selected indicators; and (ii) key informant interviews with policy makers, civil society, local leaders, and law enforcement staff. The results were synthesized around thematic areas. RESULTS: Over the first six to nine months of the pandemic, NPIs especially lockdowns, travel restrictions, curfews, school closures, and prohibition of mass gathering resulted into both positive and negative unintended consequences cutting across economic, psychological, and environmental platforms. DRC, Nigeria, and Uganda observed reduced crime rates and road traffic accidents, while Uganda also reported reduced air pollution. In addition, hygiene practices have improved through health promotion measures that have been promoted for the response to the pandemic. All countries experienced economic slowdown, job losses heavily impacting women and poor households, increased sexual and gender-based violence, teenage pregnancies, and early marriages, increased poor mental health conditions, increased waste generation with poor disposal, among others. CONCLUSION: Despite achieving pandemic control, the stringent NPIs had several negative and few positive unintended consequences. Governments need to balance the negative and positive consequences of NPIs by anticipating and instituting measures that will support and protect vulnerable groups especially the poor, the elderly, women, and children. Noticeable efforts, including measures to avoid forced into marriage, increasing inequities, economic support to urban poor; those living with disabilities, migrant workers, and refugees, had been conducted to mitigate the negative effects of the NIPs.

Impact of tiered measures on social contact and mixing patterns of in Italy during the second wave of COVID-19.

BACKGROUND: Most countries around the world enforced non-pharmaceutical interventions against COVID-19. Italy was one of the first countries to be affected by the pandemic, imposing a hard lockdown, in the first epidemic wave. During the second wave, the country implemented progressively restrictive tiers at the regional level according to weekly epidemiological risk assessments. This paper quantifies the impact of these restrictions on contacts and on the reproduction number. METHODS: Representative (with respect to age, sex, and region of residence) longitudinal surveys of the Italian population were undertaken during the second epidemic wave. Epidemiologically relevant contact patterns were measured and compared with pre-pandemic levels and according to the level of interventions experienced by the participants. Contact matrices were used to quantify the reduction in the number of contacts by age group and contact setting. The reproduction number was estimated to evaluate the impact of restrictions on the spread of COVID-19. RESULTS: The comparison with the pre-pandemic baseline shows a significant decrease in the number of contacts, independently from the age group or contact settings. This decrease in the number of contacts significantly depends on the strictness of the non-pharmaceutical interventions. For all levels of strictness considered, the reduction in social mixing results in a reproduction number smaller than one. In particular, the impact of the restriction on the number of contacts decreases with the severity of the interventions. CONCLUSIONS: The progressive restriction tiers implemented in Italy reduced the reproduction number, with stricter interventions associated with higher reductions. Readily collected contact data can inform the implementation of mitigation measures at the national level in epidemic emergencies to come.

Feasibility of return to sports assessment 6 months after patellar instability surgery.

BACKGROUND: The evidence regarding the usefulness of assessment tools to support decisions of return-to-sport after surgery for patellar instability is scarce. The purpose of this study was therefore to explore the feasibility of functional tests assessing readiness for return-to-sport six months after patellar stabilizing surgery. However, there is little evidence on what a functional assessment should include to support these decisions following surgery for patellar instability. Therefore the purpose of this study was to explore the feasibility of functional tests assessing readiness for return-to-sport six months after patellar stabilizing surgery. METHODS: In this cross-sectional study a prospective cohort of 78 patients were subjected to a range of return-to-sport readiness tests at six months after surgery for patellar instability with an "a la carte" approach. Lower Quarter Y-Balance Test (YBT-LQ), single-legged hop tests and isokinetic strength tests were performed. In addition, self-reported function was measured with the Banff Patellofemoral Instability Instrument 2.0 (BPII) and Norwich Patellar Instability score (NPI). Return-to-sport clearance criteria were defined as: ≤4 cm YBT-LQ anterior reach difference between legs, leg-symmetry-index (LSI) ≥ 95% in the YBT-LQ composite score, mean sum score LSI ≥ 85% of all single-leg hop tests and LSI ≥ 90% in isokinetic quadriceps strength. RESULTS: Sixty-four patients (82%) were able to complete all functional tests, while only eleven (14%) patients were deemed ready for return-to-sport, passing all return-to-sport clearance criteria. Patients with bilateral problems demonstrated worse performance in the contralateral leg, which resulted in higher LSI scores compared to individuals with unilateral instability. A supplementary finding was that the extent of surgery (MPFL-R only versus combined surgery) did not predict and mainly did not affect self-reported function or functional performance at the follow-up. CONCLUSION: The functional assessment used in the current study seems feasible to conduct at six months after patellar stabilizing surgery. However, current suggested clearance standards and the use of leg-symmetry-index seems inappropriate for patients with patellar instability. Therefore, further exploration of appropriate tests and return-to-sport clearance criteria is justified. TRIAL REGISTRATION: clinicaltrial.gov, NCT05119088. Registered 12.11.2021 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05119088 .

Global Trends in Social Prescribing: Web-Based Crawling Approach.

BACKGROUND: Social loneliness is a prevalent issue in industrialized countries that can lead to adverse health outcomes, including a 26% increased risk of premature mortality, coronary heart disease, stroke, depression, cognitive impairment, and Alzheimer disease. The United Kingdom has implemented a strategy to address loneliness, including social prescribing-a health care model where physicians prescribe nonpharmacological interventions to tackle social loneliness. However, there is a need for evidence-based plans for global social prescribing dissemination. OBJECTIVE: This study aims to identify global trends in social prescribing from 2018. To this end, we intend to collect and analyze words related to social prescribing worldwide and evaluate various trends of related words by classifying the core areas of social prescribing. METHODS: Google's searchable data were collected to analyze web-based data related to social prescribing. With the help of web crawling, 3796 news items were collected for the 5-year period from 2018 to 2022. Key topics were selected to identify keywords for each major topic related to social prescribing. The topics were grouped into 4 categories, namely Healthy, Program, Governance, and Target, and keywords for each topic were selected thereafter. Text mining was used to determine the importance of words collected from new data. RESULTS: Word clouds were generated for words related to social prescribing, which collected 3796 words from Google News databases, including 128 in 2018, 432 in 2019, 566 in 2020, 748 in 2021, and 1922 in 2022, increasing nearly 15-fold between 2018 and 2022 (5 years). Words such as health, prescribing, and GPs (general practitioners) were the highest in terms of frequency in the list for all the years. Between 2020 and 2021, COVID, gardening, and UK were found to be highly related words. In 2022, NHS (National Health Service) and UK ranked high. This dissertation examines social prescribing-related term frequency and classification (2018-2022) in Healthy, Program, Governance, and Target categories. Key findings include increased "Healthy" terms from 2020, "gardening" prominence in "Program," "community" growth across categories, and "Target" term spikes in 2021. CONCLUSIONS: This study's discussion highlights four key aspects: (1) the "Healthy" category trends emphasize mental health, cancer, and sleep; (2) the "Program" category prioritizes gardening, community, home-schooling, and digital initiatives; (3) "Governance" underscores the significance of community resources in social prescribing implementation; and (4) "Target" focuses on 4 main groups: individuals with long-term conditions, low-level mental health issues, social isolation, or complex social needs impacting well-being. Social prescribing is gaining global acceptance and is becoming a global national policy, as the world is witnessing a sharp rise in the aging population, noncontagious diseases, and mental health problems. A successful and sustainable model of social prescribing can be achieved by introducing social prescribing schemes based on the understanding of roles and the impact of multisectoral partnerships.

Bayesian time-varying autoregressive models of COVID-19 epidemics.

The COVID-19 pandemic has highlighted the importance of reliable statistical models which, based on the available data, can provide accurate forecasts and impact analysis of alternative policy measures. Here we propose Bayesian time-dependent Poisson autoregressive models that include time-varying coefficients to estimate the effect of policy covariates on disease counts. The model is applied to the observed series of new positive cases in Italy and in the United States. The results suggest that our proposed models are capable of capturing nonlinear growth of disease counts. We also find that policy measures and, in particular, closure policies and the distribution of vaccines, lead to a significant reduction in disease counts in both countries.

Combating COVID-19 with charisma: Evidence on governor speeches in the United States.

Using field and laboratory data, we show that leader charisma can affect COVID-related mitigating behaviors. We coded a panel of U.S. governor speeches for charisma signaling using a deep neural network algorithm. The model explains variation in stay-at-home behavior of citizens based on their smart phone data movements, showing a robust effect of charisma signaling: stay-at-home behavior increased irrespective of state-level citizen political ideology or governor party allegiance. Republican governors with a particularly high charisma signaling score impacted the outcome more relative to Democratic governors in comparable conditions. Our results also suggest that one standard deviation higher charisma signaling in governor speeches could potentially have saved 5,350 lives during the study period (02/28/2020-05/14/2020). Next, in an incentivized laboratory experiment we found that politically conservative individuals are particularly prone to believe that their co-citizens will follow governor appeals to distance or stay at home when exposed to a speech that is high in charisma; these beliefs in turn drive their preference to engage in those behaviors. These results suggest that political leaders should consider additional "soft-power" levers like charisma-which can be learned-to complement policy interventions for pandemics or other public heath crises, especially with certain populations who may need a "nudge."

Frailty, psychological well-being, and social isolation in older adults with cognitive impairment during the SARS-CoV-2 pandemic: data from the GeroCovid initiative.

BACKGROUND: The containment measures linked to the COVID-19 pandemic negatively affected the phyco-physical well-being of the population, especially older adults with neurocognitive disorders (NCDs). This study aims to evaluate whether the frailty of NCD patients was associated with different changes in multiple health domains, in particular in relation to loneliness and social isolation, pre- and post-lockdown. MATERIALS AND METHODS: Patients were recruited from 10 Italian Centers for Cognitive Disorders and Dementia. Data were collected in the pre-pandemic period (T0), during the pandemic lockdown (T1), and 6-9 months post-lockdown (T2). The UCLA Loneliness Scale-3, Activities of Daily Living (ADL), Instrumental ADL (IADL), Mini-Mental State Examination, and Neuropsychiatric Inventory (NPI) were administered. Caregivers' burden was also tested. Patients were categorized as non-frail, pre-frail, and frail according to the Fatigue, Resistance, Ambulation, Illness, and Loss of Weight scale. RESULTS: The sample included 165 subjects (61.9% women, mean age 79.5 ± 4.9 years). In the whole sample, the ADL, IADL, and NPI scores significantly declined between T0 and T2. There were no significative variations in functional and cognitive domains between the frail groups. During lockdown we recorded higher Depression Anxiety Stress Scales and Perceived Stress Scale scores in frail people. In multivariable logistic regression, frailty was associated with an increase in social isolation, and a loss of IADL. CONCLUSIONS: We observed a global deterioration in functional and neuro-psychiatric domains irrespective of the degree of frailty. Frailty was associated with the worsening of social isolation during lockdown. Frail patients and their caregivers seemed to experience more anxiety and stress disorders during SARS-CoV-2 pandemic.

[Which non pharmacological interventions should be offered to patients treated with androgen deprivation therapy for prostate cancer? A systematic review]. / Quelles interventions non médicamenteuses proposer aux patients traités par hormono-suppression pour un cancer de la prostate ? Revue systématique de la littérature.

AIM: Prostate cancer is a frequent disease and one of the main treatments used is androgen deprivation therapy, which is a therapy with disabling side effects. Non-pharmacological interventions (NPIs) are evidenced based, non-invasive interventions on human health. They are classified into five categories (physical, psychological, nutritional, digital, elemental). The NPIs sphere is booming and still remains underused in this context. METHODS: A systematic review concerning randomized controlled trials was executed according to the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). We used the "Medline" and "Kalya Research" databases. After searching and selecting eligible publications, we included 37 randomized controlled trials. RESULTS: The majority of articles concerned physical NPIs with 30 clinical studies, 3 publications dealt with nutritional NPIs, 2 with psychological NPIs and 2 articles concerned elemental NPIs. No publication about digital NPI was found. All of the studies aimed to manage and improve the side effects of treatment. No elemental NPI has demonstrated benefit. Only one psychological NPI and one nutritional NPI were effective. Five types of physical NPI protocols have shown efficacy. The main benefits related to physical abilities, body composition, osteoporosis, quality of life, fatigue, reduced cardiovascular risk and finally anxiety and depression. CONCLUSION: Non-pharmacological interventions, especially physical ones, are effective in managing and reducing the side effects associated with androgen deprivation therapy and should be offered to patients in this context.

Vaccination strategy for preventing the spread of SARS-CoV-2 in the limited supply condition: A mathematical modeling study.

To mitigate SARS-CoV-2 transmission, vaccines have been urgently approved. With their limited availability, it is critical to distribute the vaccines reasonably. We simulated the SARS-CoV-2 transmission for 365 days over four intervention periods: free transmission, structural mitigation, personal mitigation, and vaccination. Sensitivity analyses were performed to obtain robust results. We further evaluated two proposed vaccination allocations, including one-dose-high-coverage and two-doses-low-coverage, when the supply was low. 33.35% (infection rate, 2.68 in 10 million people) and 40.54% (2.36) of confirmed cases could be avoided as the nonpharmaceutical interventions (NPIs) adherence rate rose from 50% to 70%. As the vaccination coverage reached 60% and 80%, the total infections could be reduced by 32.72% and 41.19%, compared to the number without vaccination. When the durations of immunity were 90 and 120 days, the infection rates were 2.67 and 2.38. As the asymptomatic infection rate rose from 30% to 50%, the infection rate increased 0.92 (SD, 0.16) times. Conditioned on 70% adherence rate, with the same amount of limited available vaccines, the 20% and 40% vaccination coverage of one-dose-high-coverage, the infection rates were 2.70 and 2.35; corresponding to the two-doses-low-coverage with 10% and 20% vaccination coverage, the infection rates were 3.22 and 2.92. Our results indicated as the duration of immunity prolonged, the second wave of SARS-CoV-2 would be delayed and the scale would be declined. On average, the total infections in two-doses-low-coverage was 1.48 times (SD, 0.24) as high as that in one-dose-high-coverage. It is crucial to encourage people in order to improve vaccination coverage and establish immune barriers. Particularly when the supply is limited, a wiser strategy to prevent SARS-CoV-2 is equally distributing doses to the same number of individuals. Besides vaccination, NPIs are equally critical to the prevention of widespread of SARS-CoV-2.

Inferring UK COVID-19 fatal infection trajectories from daily mortality data: Were infections already in decline before the UK lockdowns?

The number of new infections per day is a key quantity for effective epidemic management. It can be estimated relatively directly by testing of random population samples. Without such direct epidemiological measurement, other approaches are required to infer whether the number of new cases is likely to be increasing or decreasing: for example, estimating the pathogen-effective reproduction number, R, using data gathered from the clinical response to the disease. For coronavirus disease 2019 (Covid-19/SARS-Cov-2), such R estimation is heavily dependent on modelling assumptions, because the available clinical case data are opportunistic observational data subject to severe temporal confounding. Given this difficulty, it is useful to retrospectively reconstruct the time course of infections from the least compromised available data, using minimal prior assumptions. A Bayesian inverse problem approach applied to UK data on first-wave Covid-19 deaths and the disease duration distribution suggests that fatal infections were in decline before full UK lockdown (24 March 2020), and that fatal infections in Sweden started to decline only a day or two later. An analysis of UK data using the model of Flaxman et al. gives the same result under relaxation of its prior assumptions on R, suggesting an enhanced role for non-pharmaceutical interventions short of full lockdown in the UK context. Similar patterns appear to have occurred in the subsequent two lockdowns.

Agitation in Cognitive Disorders: Use of the National Alzheimer's Coordinating Center Uniform Data Set (NACC-UDS) to Evaluate International Psychogeriatric Association Definition.

OBJECTIVE: Consensus-based definition of agitation by the International Psychogeriatric Association (IPA) has not been evaluated in community-based samples who are not preselected for behavioral disturbances. Here, we use a well-characterized cohort of community-dwelling older adults with cognitive impairment to assess the IPA criteria associated with agitation to evaluate the construction of this diagnostic entity. METHODS: We used the National Alzheimer Coordinating Center Unified Data Set (NACC-UDS) to construct the IPA consensus-based provisional definition of agitation in cognitive impairment (N = 19,424). We used clinician diagnosis of agitation as a gold standard in those with mild cognitive impairment and dementia and used the Neuropsychiatric Inventory-Questionnaire to define agitation symptoms and standardized assessments of function (including the Functional Assessment Scale and Clinical Dementia Rating Scale Sum of Boxes) to assess "excess disability." We also examined patterns of psychiatric comorbidities to determine if they were consistent with IPA criteria. RESULTS: There was agreement between the selected NPI measure of agitation and clinician judgment (sensitivity = 0.79, specificity = 0.69, Cohen's Kappa = 0.304). More than 84% of those with clinician judgment of agitation and 74% of those meeting the scale-based definition of agitation demonstrated excess social/functional disability. Comorbid psychiatric symptoms were present in 38% of the sample without agitation and higher in those with agitation by either definition. CONCLUSION: Agitation ranges between 15% and 48% in those with cognitive impairment. The pattern of level of excess disability and the presence of comorbid psychiatric symptoms is consistent with the profile of published definitions.

A differential of the left eye and right eye neurological pupil index is associated with discharge modified Rankin scores in neurologically injured patients.

BACKGROUND: Automated infrared pupillometry (AIP) and the Neurological Pupil index (NPi) provide an objective means of assessing and trending the pupillary light reflex (PLR) across a broad spectrum of neurological diseases. NPi quantifies the PLR and ranges from 0 to 5; in healthy individuals, the NPi of both eyes is expected to be ≥ 3.0 and symmetric. AIP values demonstrate emerging value as a prognostic tool with predictive properties that could allow practitioners to anticipate neurological deterioration and recovery. The presence of an NPi differential (a difference ≥ 0.7 between the left and right eye) is a potential sign of neurological abnormality. METHODS: We explored NPi differential by considering the modified Rankin Score at discharge (DC mRS) among patients admitted to neuroscience intensive care units (NSICU) of 4 U.S. and 1 Japanese hospitals and for two cohorts of brain injuries: stroke (including subarachnoid hemorrhage, intracerebral hemorrhage, acute ischemic stroke, and aneurysm, 1,200 total patients) and 185 traumatic brain injury (TBI) patients for a total of more than 54,000 pupillary measurements. RESULTS: Stroke patients with at least 1 occurrence of an NPi differential during their NSICU stay have higher DC mRS scores (3.9) compared to those without an NPi differential (2.7; P < .001). Patients with TBI and at least 1 occurrence of an NPi differential during their NSICU stay have higher discharge modified Rankin Scale scores (4.1) compared to those without an NPi differential (2.9; P < .001). When patients experience both abnormalities, abnormal (NPi < 3.0) and an NPi differential, the latter has an anticipatory relationship with respect to the former (P < .001 for z-score skewness analysis). Finally, our analysis confirmed ≥ 0.7 as the optimal cutoff value for the NPi differential (AUC = 0.71, P < .001). CONCLUSION: The NPi differential is an important factor that clinicians should consider when managing critically ill neurological injured patients admitted to the neurocritical care units. TRIAL REGISTRATION: NCT02804438 , Date of Registration: June 17, 2016.