Effects of a personalized nutrition program on cardiometabolic health: a randomized controlled trial.

Large variability exists in people's responses to foods. However, the efficacy of personalized dietary advice for health remains understudied. We compared a personalized dietary program (PDP) versus general advice (control) on cardiometabolic health using a randomized clinical trial. The PDP used food characteristics, individual postprandial glucose and triglyceride (TG) responses to foods, microbiomes and health history, to produce personalized food scores in an 18-week app-based program. The control group received standard care dietary advice (US Department of Agriculture Guidelines for Americans, 2020-2025) using online resources, check-ins, video lessons and a leaflet. Primary outcomes were serum low-density lipoprotein cholesterol and TG concentrations at baseline and at 18 weeks. Participants (n = 347), aged 41-70 years and generally representative of the average US population, were randomized to the PDP (n = 177) or control (n = 170). Intention-to-treat analysis (n = 347) between groups showed significant reduction in TGs (mean difference = -0.13 mmol l-1; log-transformed 95% confidence interval = -0.07 to -0.01, P = 0.016). Changes in low-density lipoprotein cholesterol were not significant. There were improvements in secondary outcomes, including body weight, waist circumference, HbA1c, diet quality and microbiome (beta-diversity) (P < 0.05), particularly in highly adherent PDP participants. However, blood pressure, insulin, glucose, C-peptide, apolipoprotein A1 and B, and postprandial TGs did not differ between groups. No serious intervention-related adverse events were reported. Following a personalized diet led to some improvements in cardiometabolic health compared to standard dietary advice. ClinicalTrials.gov registration: NCT05273268 .

Correction: Spanò et al. Effect of Dual-Task Motor-Cognitive Training in Preventing Falls in Vulnerable Elderly Cerebrovascular Patients: A Pilot Study. Brain Sci. 2022, 12, 168.

In the original publication [...].

Risk of suicide attempt with gender diversity and neurodiversity.

There is growing concern about psychiatric illness co-occurring with gender-diversity and neurodiversity, including risk of suicidal behavior. We carried out systematic reviews of research literature pertaining to suicide attempt rates in association with gender- and neurodiversity, with meta-analysis of findings. Rates of suicidal acts ranked: gender-diverse versus controls (20.1% vs. 1.90%; highly significant) > autism spectrum disorder (4.51% vs. 1.00%; highly significant) > attention deficit-hyperactivity disorder (7.52% vs. 4.09%; not significant). Attempt rates also were greater among controls who included sexual minorities (5.35% vs. 1.41%). The rate among male-to-female transgender subjects (29.1%) was slightly lower than in female-to-male subjects (30.7%), who also were encountered 24.3% more often. In sum, suicidal risk was much greater with gender-diversity than neurodiversity. Suicide attempts rate was somewhat greater among female-to-male transgender subjects. Available information was insufficient to test whether suicidal risk would be even greater among persons with both gender- and neurodiversity.

Can the Modified Frailty Index (mFI) Predict Intraoperative and Postoperative Complications in Older Women with Endometrial Cancer Undergoing Laparoscopic or Robotic Surgery? A Multicenter Observational Study.

BACKGROUND: This study aims to evaluate the strength of the association between frailty and intraoperative/postoperative complications in patients undergoing minimally invasive surgery (MIS) for endometrial cancer. METHODS: In this retrospective observational multicenter cohort study, frailty was defined beforehand by a modified frailty index (mFI) score of ≥3. Multiple logistic regressions were performed to investigate possible preoperative predictors-including frailty, age, and body mass index-of intraoperative and early (within 30 days from surgery) or delayed (beyond 30 days from surgery) postoperative complications. RESULTS: The study involved 577 women, of whom 6.9% (n = 40) were frail with an mFI ≥ 3, while 93.1% (n = 537) were non-frail with an mFI of 0-2. Frail women had a significantly higher rate of intraoperative complications (7.5% vs. 1.7%, p = 0.01), with odds 4.54 times greater (95% CI: 1.18-17.60, p = 0.028). There were no differences in the rate of early postoperative complications (15% vs. 6.9%, p = 0.06) and delayed postoperative complications (2.5% vs. 3.9%, p = 0.65) for frail versus non-frail patients. The odds of early postoperative complications increased by 0.7% (95% CI: 1.00-1.15) for every one-unit increase in age (p = 0.032). CONCLUSIONS: Frailty was associated with a significantly higher risk of intraoperative complications in older women undergoing MIS for endometrial cancer. Likewise, increasing age was an independent predictor of early postoperative complications. Our findings support the practice of assessing frailty before surgery to optimize perioperative management in this patient population.

SARS-CoV-2 infection following booster vaccination: Illness and symptom profile in a prospective, observational community-based case-control study.

BACKGROUND: Booster COVID-19 vaccines have shown efficacy in clinical trials and effectiveness in real-world data against symptomatic and severe illness. However, some people still become infected with SARS-CoV-2 following a third (booster) vaccination. This study describes the characteristics of SARS-CoV-2 illness following a third vaccination and assesses the risk of progression to symptomatic disease in SARS-CoV-2 infected individuals with time since vaccination. METHODS: This prospective, community-based, case-control study used data from UK-based, adult (≥18 years) users of the COVID Symptom Study mobile application, self-reporting a first positive COVID-19 test between June 1, 2021 and April 1, 2022. To describe the characteristics of SARS-CoV-2 illness following a third vaccination, we selected cases and controls who had received a third and second dose of monovalent vaccination against COVID-19, respectively, and reported a first positive SARS-CoV-2 test at least 7 days after most recent vaccination. Cases and controls were matched (1:1) based on age, sex, BMI, time between first vaccination and infection, and week of testing. We used logistic regression models (adjusted for age, sex, BMI, level of social deprivation and frailty) to analyse associations of disease severity, overall disease duration, and individual symptoms with booster vaccination status. To assess for potential waning of vaccine effectiveness, we compared disease severity, duration, and symptom profiles of individuals testing positive within 3 months of most recent vaccination (reference group) to profiles of individuals infected between 3 and 4, 4-5, and 5-6 months, for both third and second dose. All analyses were stratified by time period, based on the predominant SARS-CoV-2 variant at time of infection (Delta: June 1, 2021-27 Nov, 2021; Omicron: 20 Dec, 2021-Apr 1, 2022). FINDINGS: During the study period, 50,162 (Delta period) and 162,041 (Omicron) participants reported a positive SARS-CoV-2 test. During the Delta period, infection following three vaccination doses was associated with lower odds of long COVID (symptoms≥ 4 weeks) (OR=0.83, CI[0.50-1.36], p < 0.0001), hospitalisation (OR=0.55, CI[0.39-0.75], p < 0.0001) and severe symptoms (OR=0.36, CI[0.27-0.49], p < 0.0001), and higher odds of asymptomatic infection (OR=3.45, CI[2.86-4.16], p < 0.0001), compared to infection following only two vaccination doses. During the Omicron period, infection following three vaccination doses was associated with lower odds of severe symptoms (OR=0.48, CI[0.42-0.55], p < 0.0001). During the Delta period, infected individuals were less likely to report almost all individual symptoms after a third vaccination. During the Omicron period, individuals were less likely to report most symptoms after a third vaccination, except for upper respiratory symptoms e.g. sneezing (OR=1.40, CI[1.18-1.35], p < 0.0001), runny nose (OR=1.26, CI[1.18-1.35], p < 0.0001), sore throat (OR=1.17, CI[1.10-1.25], p < 0.0001), and hoarse voice (OR=1.13, CI[1.06-1.21], p < 0.0001), which were more likely to be reported. There was evidence of reduced vaccine effectiveness during both Delta and Omicron periods in those infected more than 3 months after their most recent vaccination, with increased reporting of severe symptoms, long duration illness, and most individual symptoms. INTERPRETATION: This study suggests that a third dose of monovalent vaccine may reduce symptoms, severity and duration of SARS-CoV-2 infection following vaccination. For Omicron variants, the third vaccination appears to reduce overall symptom burden but may increase upper respiratory symptoms, potentially due to immunological priming. There is evidence of waning vaccine effectiveness against progression to symptomatic and severe disease and long COVID after three months. Our findings support ongoing booster vaccination promotion amongst individuals at high risk from COVID-19, to reduce severe symptoms and duration of illness, and health system burden. Disseminating knowledge on expected symptoms following booster vaccination may encourage vaccine uptake.

Machine Learning and Pharmacogenomics at the Time of Precision Psychiatry.

Traditional medicine and biomedical sciences are reaching a turning point because of the constantly growing impact and volume of Big Data. Machine Learning (ML) techniques and related algorithms play a central role as diagnostic, prognostic, and decision-making tools in this field. Another promising area becoming part of everyday clinical practice is personalized therapy and pharmacogenomics. Applying ML to pharmacogenomics opens new frontiers to tailored therapeutical strategies to help clinicians choose drugs with the best response and fewer side effects, operating with genetic information and combining it with the clinical profile. This systematic review aims to draw up the state-of-the-art ML applied to pharmacogenomics in psychiatry. Our research yielded fourteen papers; most were published in the last three years. The sample comprises 9,180 patients diagnosed with mood disorders, psychoses, or autism spectrum disorders. Prediction of drug response and prediction of side effects are the most frequently considered domains with the supervised ML technique, which first requires training and then testing. The random forest is the most used algorithm; it comprises several decision trees, reduces the training set's overfitting, and makes precise predictions. ML proved effective and reliable, especially when genetic and biodemographic information were integrated into the algorithm. Even though ML and pharmacogenomics are not part of everyday clinical practice yet, they will gain a unique role in the next future in improving personalized treatments in psychiatry.

Profiling post-COVID-19 condition across different variants of SARS-CoV-2: a prospective longitudinal study in unvaccinated wild-type, unvaccinated alpha-variant, and vaccinated delta-variant populations.

BACKGROUND: Self-reported symptom studies rapidly increased understanding of SARS-CoV-2 during the COVID-19 pandemic and enabled monitoring of long-term effects of COVID-19 outside hospital settings. Post-COVID-19 condition presents as heterogeneous profiles, which need characterisation to enable personalised patient care. We aimed to describe post-COVID-19 condition profiles by viral variant and vaccination status. METHODS: In this prospective longitudinal cohort study, we analysed data from UK-based adults (aged 18-100 years) who regularly provided health reports via the Covid Symptom Study smartphone app between March 24, 2020, and Dec 8, 2021. We included participants who reported feeling physically normal for at least 30 days before testing positive for SARS-CoV-2 who subsequently developed long COVID (ie, symptoms lasting longer than 28 days from the date of the initial positive test). We separately defined post-COVID-19 condition as symptoms that persisted for at least 84 days after the initial positive test. We did unsupervised clustering analysis of time-series data to identify distinct symptom profiles for vaccinated and unvaccinated people with post-COVID-19 condition after infection with the wild-type, alpha (B.1.1.7), or delta (B.1.617.2 and AY.x) variants of SARS-CoV-2. Clusters were then characterised on the basis of symptom prevalence, duration, demography, and previous comorbidities. We also used an additional testing sample with additional data from the Covid Symptom Study Biobank (collected between October, 2020, and April, 2021) to investigate the effects of the identified symptom clusters of post-COVID-19 condition on the lives of affected people. FINDINGS: We included 9804 people from the COVID Symptom Study with long COVID, 1513 (15%) of whom developed post-COVID-19 condition. Sample sizes were sufficient only for analyses of the unvaccinated wild-type, unvaccinated alpha variant, and vaccinated delta variant groups. We identified distinct profiles of symptoms for post-COVID-19 condition within and across variants: four endotypes were identified for infections due to the wild-type variant (in unvaccinated people), seven for the alpha variant (in unvaccinated people), and five for the delta variant (in vaccinated people). Across all variants, we identified a cardiorespiratory cluster of symptoms, a central neurological cluster, and a multi-organ systemic inflammatory cluster. These three main clusers were confirmed in a testing sample. Gastrointestinal symptoms clustered in no more than two specific phenotypes per viral variant. INTERPRETATION: Our unsupervised analysis identified different profiles of post-COVID-19 condition, characterised by differing symptom combinations, durations, and functional outcomes. Our classification could be useful for understanding the distinct mechanisms of post-COVID-19 condition, as well as for identification of subgroups of individuals who might be at risk of prolonged debilitation. FUNDING: UK Government Department of Health and Social Care, Chronic Disease Research Foundation, The Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging & Artificial Intelligence Centre for Value-Based Healthcare, UK National Institute for Health Research, UK Medical Research Council, British Heart Foundation, UK Alzheimer's Society, and ZOE.

Lung-protective ventilation during Trendelenburg pneumoperitoneum surgery: A randomized clinical trial.

Study objective To assess the effects of a protective ventilation strategy during Trendelenburg pneumoperitoneum surgery on postoperative oxygenation. DESIGNS: Parallel-group, randomized trial. SETTING: Operating room of a university hospital, Italy. PATIENTS: Morbidly obese patients undergoing Trendelenburg pneumoperitoneum gynaecological surgery. INTERVENTIONS: Participants were randomized to standard (SV: tidal volume = 10 ml/kg of predicted body weight, PEEP = 5 cmH2O) or protective (PV: tidal volume = 6 ml/kg of predicted body weight, PEEP = 10 cmH2O, recruitment maneuvers) ventilation during anesthesia. MEASUREMENTS: Primary outcome was PaO2/FiO2 one hour after extubation. Secondary outcomes included day-1 PaO2/FiO2, day-2 respiratory function and intraoperative respiratory/lung mechanics, assessed through esophageal manometry, end-expiratory lung volume (EELV) measurement and pressure-volume curves. MAIN RESULTS: Sixty patients were analyzed (31 in SV group, 29 in PV group). Median [IqR] tidal volume was 350 ml [300-360] in PV group and 525 [500-575] in SV group. Median PaO2/FiO2 one hour after extubation was 280 mmHg [246-364] in PV group vs. 298 [250-343] in SV group (p = 0.64). Day-1 PaO2/FiO2, day-2 forced vital capacity, FEV-1 and Tiffenau Index were not different between groups (all p > 0.10). Intraoperatively, 59% of patients showed complete airway closure during pneumoperitoneum, without difference between groups: median airway opening pressure was 17 cmH2O. In PV group, airway and transpulmonary driving pressure were lower (12 ± 5 cmH2O vs. 17 ± 7, p < 0.001; 9 ± 4 vs. 13 ± 7, p < 0.001), PaCO2 and respiratory rate were higher (48 ± 8 mmHg vs. 42 ± 12, p < 0.001; 23 ± 5 breaths/min vs. 16 ± 4, p < 0.001). Intraoperative EELV was similar between PV and SV group (1193 ± 258 ml vs. 1207 ± 368, p = 0.80); ratio of tidal volume to EELV was lower in PV group (0.45 ± 0.12 vs. 0.32 ± 0.09, p < 0.001). CONCLUSIONS: In obese patients undergoing Trendelenburg pneumoperitoneum surgery, PV did not improve postoperative oxygenation nor day-2 respiratory function. PV was associated with intraoperative respiratory mechanics indicating less injurious ventilation. The high prevalence of complete airway closure may have affected study results. TRIAL REGISTRATION: Prospectively registered on http://clinicaltrials.govNCT03157479 on May 17th, 2017.

The Effectiveness of Mobile Apps for Monitoring and Management of Suicide Crisis: A Systematic Review of the Literature.

Suicide risk is a multifaceted phenomenon, and many risk factors are involved in its complexity. In the last few decades, mental health apps have spread, providing economic and affordable strategies to prevent suicide. Therefore, the aim of this review is to identify original studies on mobile apps that target suicidal crises. The review follows PRISMA guidelines, searching through four major electronic databases (PubMed/MEDLINE, Scopus, PsycInfo and Web of Science) for relevant titles/abstracts published from January 2010 to May 2022. It includes original studies that explicitly analyze mobile apps for suicide prevention. A total of 32 studies met the inclusion criteria. Sixteen studies assessed the feasibility and acceptability of mobile apps, ten studies assessed the efficacy of mobile apps in preventing suicide, and six studies described randomized control trial protocols not yet implemented. Generally, the apps were judged by participants to be acceptable and helpful, and several improvements to enhance the functionality of apps were suggested. The efficacy of mobile apps, although limited and assessed with very heterogenous methods, was confirmed by most of the studies. Mobile apps could represent a helpful supplement to traditional prevention tactics, providing real-time monitoring of at-risk persons, personalized tools to cope with suicidal crises, and immediate access to specific support.

The Effect of Dual-Task Motor-Cognitive Training in Adults with Neurological Diseases Who Are at Risk of Falling.

Falls are common in patients with neurological diseases and can be very problematic. Recently, there has been an increase in fall prevention research in people with neurological diseases; however, these studies are usually condition-specific (e.g., only MS, PD or stroke). Here, our aim was to evaluate and compare the efficacy of an advanced and innovative dual-task, motor-cognitive rehabilitation program in individuals with different neurological diseases who are at risk of falling. We recruited 95 consecutive adults with neurological diseases who are at risk of falling and divided them into four groups: 31 with cerebrovascular disease (CVD), 20 with Parkinson's disease (PD), 23 with traumatic brain injury (TBI) and 21 with other neurological diseases (OND). Each patient completed a dual-task, motor-cognitive training program and underwent two test evaluations to assess balance, gait, fear of falling and walking performance at the pre-and post-intervention. We found that our experimental motor-cognitive, dual-task rehabilitation program was an effective method for improving walking balance, gait, walking endurance and speed, and fear of falling, and that it reduced the risk of falls in patients with different neurological diseases. This study presents an alternative approach for people with chronic neurological diseases and provides innovative data for managing this population.

Differentiation and comorbidity of bipolar disorder and attention deficit and hyperactivity disorder in children, adolescents, and adults: A clinical and nosological perspective.

Bipolar Disorder (BD) and Attention Deficit and Hyperactivity Disorder (ADHD) are mental disorders with high degree of lifetime comorbidity. Both BD and ADHD are disorders with onset in childhood and early adolescence. Both disorders are often undiagnosed, misdiagnosed, and sometimes overdiagnosed, leading to high rates of morbidity and disability. The psychiatric and behavioral symptoms associated with ADHD and BD have significant overlap. Albeit the existence of a large body of literature, it is far from being clear whether comorbidity can be explained by the confounding overlap of operationally defined criteria or whether it reflects a genuine comorbidity of two biologically distinct disorders. The aim of this paper is to recognize and/or differentiate the pattern of ADHD across the course of BD from a nosological point of view, focusing on specific clinical and neurobiological dimensions. We found that some critical issues may help to fulfill the purpose of our perspective. We suggest that the relationship between ADHD and BD, based on clinical, developmental, and epidemiological commonalities, can be better clarified using four different scenarios.

Post-vaccination infection rates and modification of COVID-19 symptoms in vaccinated UK school-aged children and adolescents: A prospective longitudinal cohort study.

Background: We aimed to explore the effectiveness of one-dose BNT162b2 vaccination upon SARS-CoV-2 infection, its effect on COVID-19 presentation, and post-vaccination symptoms in children and adolescents (CA) in the UK during periods of Delta and Omicron variant predominance. Methods: In this prospective longitudinal cohort study, we analysed data from 115,775 CA aged 12-17 years, proxy-reported through the Covid Symptom Study (CSS) smartphone application. We calculated post-vaccination infection risk after one dose of BNT162b2, and described the illness profile of CA with post-vaccination SARS-CoV-2 infection, compared to unvaccinated CA, and post-vaccination side-effects. Findings: Between August 5, 2021 and February 14, 2022, 25,971 UK CA aged 12-17 years received one dose of BNT162b2 vaccine. The probability of testing positive for infection diverged soon after vaccination, and was lower in CA with prior SARS-CoV-2 infection. Vaccination reduced proxy-reported infection risk (-80·4% (95% CI -0·82 -0·78) and -53·7% (95% CI -0·62 -0·43) at 14-30 days with Delta and Omicron variants respectively, and -61·5% (95% CI -0·74 -0·44) and -63·7% (95% CI -0·68 -0.59) after 61-90 days). Vaccinated CA who contracted SARS-CoV-2 during the Delta period had milder disease than unvaccinated CA; during the Omicron period this was only evident in children aged 12-15 years. Overall disease profile was similar in both vaccinated and unvaccinated CA. Post-vaccination local side-effects were common, systemic side-effects were uncommon, and both resolved within few days (3 days in most cases). Interpretation: One dose of BNT162b2 vaccine reduced risk of SARS-CoV-2 infection for at least 90 days in CA aged 12-17 years. Vaccine protection varied for SARS-CoV-2 variant type (lower for Omicron than Delta variant), and was enhanced by pre-vaccination SARS-CoV-2 infection. Severity of COVID-19 presentation after vaccination was generally milder, although unvaccinated CA also had generally mild disease. Overall, vaccination was well-tolerated. Funding: UK Government Department of Health and Social Care, Chronic Disease Research Foundation, The Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging & Artificial Intelligence Centre for Value Based Healthcare, UK National Institute for Health Research, UK Medical Research Council, British Heart Foundation and Alzheimer's Society, and ZOE Limited.

COVID-19 vaccine waning and effectiveness and side-effects of boosters: a prospective community study from the ZOE COVID Study.

BACKGROUND: With the surge of new SARS-CoV-2 variants, countries have begun offering COVID-19 vaccine booster doses to high-risk groups and, more recently, to the adult population in general. However, uncertainty remains over how long primary vaccination series remain effective, the ideal timing for booster doses, and the safety of heterologous booster regimens. We aimed to investigate COVID-19 primary vaccine series effectiveness and its waning, and the safety and effectiveness of booster doses, in a UK community setting. METHODS: We used SARS-CoV-2 positivity rates in individuals from a longitudinal, prospective, community-based study (ZOE COVID Study), in which data were self-reported through an app, to assess the effectiveness of three COVID-19 vaccines (ChAdOx1 nCov19 [Oxford-AstraZeneca], BNT162b2 [Pfizer-BioNtech], and mRNA1273 [Moderna]) against infection in the 8 months after completion of primary vaccination series. In individuals receiving boosters, we investigated vaccine effectiveness and reactogenicity, by assessing 16 self-reported systemic and localised side-effects. We used multivariate Poisson regression models adjusting for confounders to estimate vaccine effectiveness. FINDINGS: We included 620 793 participants who received two vaccine doses (204 731 [33·0%] received BNT162b2, 405 239 [65·3%] received ChAdOx1 nCoV-19, and 10 823 [1·7%] received mRNA-1273) and subsequently had a SARS-CoV-2 test result between May 23 (chosen to exclude the period of alpha [B.1.1.7] variant dominance) and Nov 23, 2021. 62 172 (10·0%) vaccinated individuals tested positive for SARS-CoV-2 and were compared with 40 345 unvaccinated controls (6726 [16·7%] of whom tested positive). Vaccine effectiveness waned after the second dose: at 5 months, BNT162b2 effectiveness was 82·1% (95% CI 81·3-82·9), ChAdOx1 nCoV-19 effectiveness was 75·7% (74·9-76·4), and mRNA-1273 effectiveness was 84·3% (81·2-86·9). Vaccine effectiveness decreased more among individuals aged 55 years or older and among those with comorbidities. 135 932 individuals aged 55 years or older received a booster (2123 [1·6%] of whom tested positive). Vaccine effectiveness for booster doses in 0-3 months after BNT162b2 primary vaccination was higher than 92·5%, and effectiveness for heterologous boosters after ChAdOx1 nCoV-19 was at least 88·8%. For the booster reactogenicity analysis, in 317 011 participants, the most common systemic symptom was fatigue (in 31 881 [10·1%] participants) and the most common local symptom was tenderness (in 187 767 [59·2%]). Systemic side-effects were more common for heterologous schedules (32 632 [17·9%] of 182 374) than for homologous schedules (17 707 [13·2%] of 134 637; odds ratio 1·5, 95% CI 1·5-1·6, p<0·0001). INTERPRETATION: After 5 months, vaccine effectiveness remained high among individuals younger than 55 years. Booster doses restore vaccine effectiveness. Adverse reactions after booster doses were similar to those after the second dose. Homologous booster schedules had fewer reported systemic side-effects than heterologous boosters. FUNDING: Wellcome Trust, ZOE, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, Medical Research Council.

Symptom prevalence, duration, and risk of hospital admission in individuals infected with SARS-CoV-2 during periods of omicron and delta variant dominance: a prospective observational study from the ZOE COVID Study.

BACKGROUND: The SARS-CoV-2 variant of concern, omicron, appears to be less severe than delta. We aim to quantify the differences in symptom prevalence, risk of hospital admission, and symptom duration among the vaccinated population. METHODS: In this prospective longitudinal observational study, we collected data from participants who were self-reporting test results and symptoms in the ZOE COVID app (previously known as the COVID Symptoms Study App). Eligible participants were aged 16-99 years, based in the UK, with a body-mass index between 15 and 55 kg/m2, had received at least two doses of any SARS-CoV-2 vaccine, were symptomatic, and logged a positive symptomatic PCR or lateral flow result for SARS-CoV-2 during the study period. The primary outcome was the likelihood of developing a given symptom (of the 32 monitored in the app) or hospital admission within 7 days before or after the positive test in participants infected during omicron prevalence compared with those infected during delta prevalence. FINDINGS: Between June 1, 2021, and Jan 17, 2022, we identified 63 002 participants who tested positive for SARS-CoV-2 and reported symptoms in the ZOE app. These patients were matched 1:1 for age, sex, and vaccination dose, across two periods (June 1 to Nov 27, 2021, delta prevalent at >70%; n=4990, and Dec 20, 2021, to Jan 17, 2022, omicron prevalent at >70%; n=4990). Loss of smell was less common in participants infected during omicron prevalence than during delta prevalence (16·7% vs 52·7%, odds ratio [OR] 0·17; 95% CI 0·16-0·19, p<0·001). Sore throat was more common during omicron prevalence than during delta prevalence (70·5% vs 60·8%, 1·55; 1·43-1·69, p<0·001). There was a lower rate of hospital admission during omicron prevalence than during delta prevalence (1·9% vs 2·6%, OR 0·75; 95% CI 0·57-0·98, p=0·03). INTERPRETATION: The prevalence of symptoms that characterise an omicron infection differs from those of the delta SARS-CoV-2 variant, apparently with less involvement of the lower respiratory tract and reduced probability of hospital admission. Our data indicate a shorter period of illness and potentially of infectiousness which should impact work-health policies and public health advice. FUNDING: Wellcome Trust, ZOE, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, and Medical Research Council.

Effect of Dual-Task Motor-Cognitive Training in Preventing Falls in Vulnerable Elderly Cerebrovascular Patients: A Pilot Study.

Falling is a frequent and major clinical problem among older adults, as well as in patients with chronic cerebrovascular diseases (CVD). At present, sequential (mixed) and simultaneously (dual-task) motor-cognitive trainings are the best approaches to affording patients more autonomy in their everyday motor independence while reducing fall risks and consequences. The objective of this study was to evaluate the efficacy of an advanced and innovative dual-task motor-cognitive rehabilitation program on fall risks in vulnerable older persons with chronic CVD. To this purpose, 26 consecutive older fallers with chronic CVD were recruited, and completed a mixed motor-cognitive or a dual-task motor-cognitive training program. Each patient also underwent two test evaluations to assess balance, gait, fear of falling, and walking performance at pre-and post-intervention. We found that our experimental motor-cognitive dual-task rehabilitation program could be an effective method to improve walking balance, gait, walking speed, and fear of falling, while reducing the risk of falls in older people with chronic CVD. Furthermore, results show that the simultaneous motor-cognitive training is more effective than the sequential motor-cognitive training. Therefore, our study brings innovative data, which can contribute positively to the management of this population.

Self-reported COVID-19 vaccine hesitancy and uptake among participants from different racial and ethnic groups in the United States and United Kingdom.

Worldwide, racial and ethnic minorities have been disproportionately impacted by COVID-19 with increased risk of infection, its related complications, and death. In the initial phase of population-based vaccination in the United States (U.S.) and United Kingdom (U.K.), vaccine hesitancy may result in differences in uptake. We performed a cohort study among U.S. and U.K. participants who volunteered to take part in the smartphone-based COVID Symptom Study (March 2020-February 2021) and used logistic regression to estimate odds ratios of vaccine hesitancy and uptake. In the U.S. (n = 87,388), compared to white participants, vaccine hesitancy was greater for Black and Hispanic participants and those reporting more than one or other race. In the U.K. (n = 1,254,294), racial and ethnic minority participants showed similar levels of vaccine hesitancy to the U.S. However, associations between participant race and ethnicity and levels of vaccine uptake were observed to be different in the U.S. and the U.K. studies. Among U.S. participants, vaccine uptake was significantly lower among Black participants, which persisted among participants that self-reported being vaccine-willing. In contrast, statistically significant racial and ethnic disparities in vaccine uptake were not observed in the U.K sample. In this study of self-reported vaccine hesitancy and uptake, lower levels of vaccine uptake in Black participants in the U.S. during the initial vaccine rollout may be attributable to both hesitancy and disparities in access.

Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study.

BACKGROUND: COVID-19 vaccines show excellent efficacy in clinical trials and effectiveness in real-world data, but some people still become infected with SARS-CoV-2 after vaccination. This study aimed to identify risk factors for post-vaccination SARS-CoV-2 infection and describe the characteristics of post-vaccination illness. METHODS: This prospective, community-based, nested, case-control study used self-reported data (eg, on demographics, geographical location, health risk factors, and COVID-19 test results, symptoms, and vaccinations) from UK-based, adult (≥18 years) users of the COVID Symptom Study mobile phone app. For the risk factor analysis, cases had received a first or second dose of a COVID-19 vaccine between Dec 8, 2020, and July 4, 2021; had either a positive COVID-19 test at least 14 days after their first vaccination (but before their second; cases 1) or a positive test at least 7 days after their second vaccination (cases 2); and had no positive test before vaccination. Two control groups were selected (who also had not tested positive for SARS-CoV-2 before vaccination): users reporting a negative test at least 14 days after their first vaccination but before their second (controls 1) and users reporting a negative test at least 7 days after their second vaccination (controls 2). Controls 1 and controls 2 were matched (1:1) with cases 1 and cases 2, respectively, by the date of the post-vaccination test, health-care worker status, and sex. In the disease profile analysis, we sub-selected participants from cases 1 and cases 2 who had used the app for at least 14 consecutive days after testing positive for SARS-CoV-2 (cases 3 and cases 4, respectively). Controls 3 and controls 4 were unvaccinated participants reporting a positive SARS-CoV-2 test who had used the app for at least 14 consecutive days after the test, and were matched (1:1) with cases 3 and 4, respectively, by the date of the positive test, health-care worker status, sex, body-mass index (BMI), and age. We used univariate logistic regression models (adjusted for age, BMI, and sex) to analyse the associations between risk factors and post-vaccination infection, and the associations of individual symptoms, overall disease duration, and disease severity with vaccination status. FINDINGS: Between Dec 8, 2020, and July 4, 2021, 1 240 009 COVID Symptom Study app users reported a first vaccine dose, of whom 6030 (0·5%) subsequently tested positive for SARS-CoV-2 (cases 1), and 971 504 reported a second dose, of whom 2370 (0·2%) subsequently tested positive for SARS-CoV-2 (cases 2). In the risk factor analysis, frailty was associated with post-vaccination infection in older adults (≥60 years) after their first vaccine dose (odds ratio [OR] 1·93, 95% CI 1·50-2·48; p<0·0001), and individuals living in highly deprived areas had increased odds of post-vaccination infection following their first vaccine dose (OR 1·11, 95% CI 1·01-1·23; p=0·039). Individuals without obesity (BMI <30 kg/m2) had lower odds of infection following their first vaccine dose (OR 0·84, 95% CI 0·75-0·94; p=0·0030). For the disease profile analysis, 3825 users from cases 1 were included in cases 3 and 906 users from cases 2 were included in cases 4. Vaccination (compared with no vaccination) was associated with reduced odds of hospitalisation or having more than five symptoms in the first week of illness following the first or second dose, and long-duration (≥28 days) symptoms following the second dose. Almost all symptoms were reported less frequently in infected vaccinated individuals than in infected unvaccinated individuals, and vaccinated participants were more likely to be completely asymptomatic, especially if they were 60 years or older. INTERPRETATION: To minimise SARS-CoV-2 infection, at-risk populations must be targeted in efforts to boost vaccine effectiveness and infection control measures. Our findings might support caution around relaxing physical distancing and other personal protective measures in the post-vaccination era, particularly around frail older adults and individuals living in more deprived areas, even if these individuals are vaccinated, and might have implications for strategies such as booster vaccinations. FUNDING: ZOE, the UK Government Department of Health and Social Care, the Wellcome Trust, the UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging and Artificial Intelligence Centre for Value Based Healthcare, the UK National Institute for Health Research, the UK Medical Research Council, the British Heart Foundation, and the Alzheimer's Society.

Disentangling post-vaccination symptoms from early COVID-19.

BACKGROUND: Identifying and testing individuals likely to have SARS-CoV-2 is critical for infection control, including post-vaccination. Vaccination is a major public health strategy to reduce SARS-CoV-2 infection globally. Some individuals experience systemic symptoms post-vaccination, which overlap with COVID-19 symptoms. This study compared early post-vaccination symptoms in individuals who subsequently tested positive or negative for SARS-CoV-2, using data from the COVID Symptom Study (CSS) app. METHODS: We conducted a prospective observational study in 1,072,313 UK CSS participants who were asymptomatic when vaccinated with Pfizer-BioNTech mRNA vaccine (BNT162b2) or Oxford-AstraZeneca adenovirus-vectored vaccine (ChAdOx1 nCoV-19) between 8 December 2020 and 17 May 2021, who subsequently reported symptoms within seven days (N=362,770) (other than local symptoms at injection site) and were tested for SARS-CoV-2 (N=14,842), aiming to differentiate vaccination side-effects per se from superimposed SARS-CoV-2 infection. The post-vaccination symptoms and SARS-CoV-2 test results were contemporaneously logged by participants. Demographic and clinical information (including comorbidities) were recorded. Symptom profiles in individuals testing positive were compared with a 1:1 matched population testing negative, including using machine learning and multiple models considering UK testing criteria. FINDINGS: Differentiating post-vaccination side-effects alone from early COVID-19 was challenging, with a sensitivity in identification of individuals testing positive of 0.6 at best. Most of these individuals did not have fever, persistent cough, or anosmia/dysosmia, requisite symptoms for accessing UK testing; and many only had systemic symptoms commonly seen post-vaccination in individuals negative for SARS-CoV-2 (headache, myalgia, and fatigue). INTERPRETATION: Post-vaccination symptoms per se cannot be differentiated from COVID-19 with clinical robustness, either using symptom profiles or machine-derived models. Individuals presenting with systemic symptoms post-vaccination should be tested for SARS-CoV-2 or quarantining, to prevent community spread. FUNDING: UK Government Department of Health and Social Care, Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK National Institute for Health Research, UK Medical Research Council and British Heart Foundation, Chronic Disease Research Foundation, Zoe Limited.

Early detection of COVID-19 in the UK using self-reported symptoms: a large-scale, prospective, epidemiological surveillance study.

BACKGROUND: Self-reported symptoms during the COVID-19 pandemic have been used to train artificial intelligence models to identify possible infection foci. To date, these models have only considered the culmination or peak of symptoms, which is not suitable for the early detection of infection. We aimed to estimate the probability of an individual being infected with SARS-CoV-2 on the basis of early self-reported symptoms to enable timely self-isolation and urgent testing. METHODS: In this large-scale, prospective, epidemiological surveillance study, we used prospective, observational, longitudinal, self-reported data from participants in the UK on 19 symptoms over 3 days after symptoms onset and COVID-19 PCR test results extracted from the COVID-19 Symptom Study mobile phone app. We divided the study population into a training set (those who reported symptoms between April 29, 2020, and Oct 15, 2020) and a test set (those who reported symptoms between Oct 16, 2020, and Nov 30, 2020), and used three models to analyse the self-reported symptoms: the UK's National Health Service (NHS) algorithm, logistic regression, and the hierarchical Gaussian process model we designed to account for several important variables (eg, specific COVID-19 symptoms, comorbidities, and clinical information). Model performance to predict COVID-19 positivity was compared in terms of sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) in the test set. For the hierarchical Gaussian process model, we also evaluated the relevance of symptoms in the early detection of COVID-19 in population subgroups stratified according to occupation, sex, age, and body-mass index. FINDINGS: The training set comprised 182 991 participants and the test set comprised 15 049 participants. When trained on 3 days of self-reported symptoms, the hierarchical Gaussian process model had a higher prediction AUC (0·80 [95% CI 0·80-0·81]) than did the logistic regression model (0·74 [0·74-0·75]) and the NHS algorithm (0·67 [0·67-0·67]). AUCs for all models increased with the number of days of self-reported symptoms, but were still high for the hierarchical Gaussian process model at day 1 (0·73 [95% CI 0·73-0·74]) and day 2 (0·79 [0·78-0·79]). At day 3, the hierarchical Gaussian process model also had a significantly higher sensitivity, but a non-statistically lower specificity, than did the two other models. The hierarchical Gaussian process model also identified different sets of relevant features to detect COVID-19 between younger and older subgroups, and between health-care workers and non-health-care workers. When used during different pandemic periods, the model was robust to changes in populations. INTERPRETATION: Early detection of SARS-CoV-2 infection is feasible with our model. Such early detection is crucial to contain the spread of COVID-19 and efficiently allocate medical resources. FUNDING: ZOE, the UK Government Department of Health and Social Care, the Wellcome Trust, the UK Engineering and Physical Sciences Research Council, the UK National Institute for Health Research, the UK Medical Research Council, the British Heart Foundation, the Alzheimer's Society, the Chronic Disease Research Foundation, and the Massachusetts Consortium on Pathogen Readiness.