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IntroductionExpansion in digital health using mobile phone health applications has increased recently. We developed a mobile phone application (Aintree Heart Failure Passport-AHFP APP) for heart failure (HF) patient education, self-care and improved medication adherence. MethodsThis was a prospective observational study of patients with acute decompensated HF managed with day-case intravenous diuretics in a HF specialist nurse delivered Ambulatory Acute Heart Failure Unit (AAHFU) in a British university hospital during the ongoing COVID-19 pandemic (March 2020 to July 2021). We assessed self-care behaviour (European Heart Failure Self-care Behaviour scale - EHFSBs-9) and medication adherence (Medication Adherence Report Scale -MARS-5) at 2 weeks post-presentation in patients who utilised the AHFP APP and compared 30-day HF re-admissions with annual hospital HF data. Results148 out of 221 consecutive ADHF patients treated in the AAHFU downloaded the AHFP Mobile APP. 45% were women and mean age of the cohort 62 {+/-} 6.1 years. 55% patients had HF with reduced ejection fraction (HFrEF), 34% had HF with preserved EF (HFpEF) and 11% had HF with mildly reduced EF. Mean EHFSBs-9 was 19.1{+/-}6.7; mean MARS-5 score 23.3{+/-}1.HF 30 day re-hospitalisation incidence significantly lower (11%) in the APP cohort compared to the incidence of 19% amongst all patients with ADHF during the study period (p=0.02). ConclusionsOur pilot feasibility study suggests that use of a HF educational self-care mobile phone APP in ADHF patients during the COVID pandemic, leads to high quality self-care behaviour, high medication adherence and also lower levels of 30-day HF re-hospitalisation. These results will need to be validated in a randomised controlled trial. 3 Key PointsO_LIThe use of digital healthcare technologies such as mobile APPs, is rapidly increasing C_LIO_LIThis study analyses the role of our heart failure educational and self-care mobile APP, used by patients with acute decompensated heart failure during the COVID-19 pandemic C_LIO_LIOur results show that use of the mobile APP can lead to high levels of self-care, medication adherence and also reduced 30 day readmissions C_LI
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BackgroundMolnupiravir was licensed for treating high-risk patients with COVID-19 based on data from unvaccinated adults. AGILE CST-2 (NCT04746183) Phase II reports safety and virological efficacy of molnupiravir in vaccinated and unvaccinated individuals. MethodsAdult out-patients with PCR-confirmed SARS-CoV-2 infection within five days of symptom onset were randomly assigned 1:1 to receive molnupiravir (800mg twice daily for five days) or placebo. The primary outcome was time to swab PCR-negativity, compared using a Bayesian model for estimating the probability of a superior virological response (Hazard Ratio>1) for molnupiravir over placebo. Secondary outcomes included change in viral titre at day 5, safety and tolerability, clinical progression and patient reported outcome measures. We analysed outcomes after the last participant reached day 29. FindingsOf 180 participants randomised (90 molnupiravir, 90 placebo), 50% were vaccinated. Infections with SARS-CoV-2 variants Delta (40%), Alpha (21%), Omicron (21%) and EU1 (16%) were represented. The median time to negative-PCR was 8 versus 11 days for molnupiravir and placebo (HR=1{middle dot}30, 95% CrI 0{middle dot}92-1{middle dot}71, p=0{middle dot}07 by Logrank and p=0{middle dot}03 by Breslow-Gehan tests). Although small numbers precluded subgroup analysis, no obvious differences were observed between vaccinated and unvaccinated participants. Using a two-point prior the probability of molnupiravir being superior to placebo (HR>1) was 75{middle dot}4%, which was just below our defined threshold of 80% for establishing superiority. Using an uninformative continuous prior, the probability of HR>1 was 94{middle dot}7%. As an exploratory analysis, the change in viral titre on day 5 (end of treatment) was significantly greater with molnupiravir compared with placebo. A total of 4 participants reported severe adverse events (grade 3+), 3 of whom were in the placebo arm. InterpretationWe found molnupiravir to be well-tolerated, with evidence for high probability of antiviral efficacy in a population of vaccinated and unvaccinated individuals infected with a broad range of viral variants. FundingFunded by Ridgeback Biotherapeutics and UK National Institute for Health and Care Research infrastructure funding. The AGILE platform infrastructure is supported by the Medical Research Council (grant number MR/V028391/1) and the Wellcome Trust (grant number 221590/Z/20/Z).
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{beta}-d-N4-hydroxycytidine (NHC), the parent nucleoside of molnupiravir, a COVID-19 antiviral, was quantified at sites of SARS-CoV-2 transmission in twelve patients enrolled in AGILE CST-2 (NCT04746183). Saliva, nasal and tear concentrations were 3, 21 and 22% that of plasma. Saliva and nasal NHC concentrations were significantly correlated with plasma (p<0.0001).
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PurposePopulation surveys underrepresent people with severe mental ill health. This paper aims to explore perceived social support and loneliness and factor associations during the Covid-19 pandemic in a sample of individuals with severe mental ill health. Design/methodology/approachWe sampled an already existing cohort of people with severe mental ill health. Researchers contacted participants by phone or by post to invite them to take part in a survey about how the pandemic restrictions had impacted health, Covid-19 experiences, perceived social support, employment and loneliness. Loneliness was measured by the three item UCLA loneliness scale. FindingsIn the pandemic sub-cohort, 367 adults with a severe mental ill health diagnosis completed a remote survey. 29-34% of participants reported being lonely. Loneliness was associated with being younger in age (adjusted OR = -.98, p = .02), living alone (adjusted OR = 2.04, p = .01), high levels of social and economic deprivation (adjusted OR = 2.49, p = .04), and lower perceived social support (B = -5.86, p < .001). Living alone was associated with lower perceived social support. Being lonely was associated with a self-reported deterioration in mental health during the pandemic (adjusted OR = 3.46, 95%CI 2.03-5.91). Practical implicationsIntervention strategies to tackle loneliness in the severe mental ill health population are needed. Further research is needed to follow-up the severe mental ill health population after pandemic restrictions are lifted to understand perceived social support and loneliness trends. OriginalityLoneliness was a substantial problem for the severe mental ill health population before the Covid-19 pandemic but there is limited evidence to understand perceived social support and loneliness trends during the pandemic.
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BackgroundRestrictions due to the COVID-19 pandemic have led to everyday reliance on digitalisation of life, including access to health care services. People with severe mental ill health (SMI - e.g., bipolar or psychosis spectrum disorders) are at greater risk for digital exclusion and it is unknown to what extent they are able to adapt to online service delivery. This cross-sectional survey study explored use of the Internet and digital devices during the pandemic restrictions and its association with physical and mental health changes. Methods367 adults with an SMI diagnosis completed a survey (online or offline) and provided information on access to Internet connection and devices, internet skills, online activities, and barriers to using the Internet. They also self-reported changes in mental and physical health. ResultsDuring the pandemic restrictions 61.6% were limited or non-users of the Internet. The majority had access to the Internet and digital devices but around half reported knowledge deficits. Most common activities were accessing information and entertainment (88.9%), staying in touch with friends and families (84.8%), and purchasing goods (other than food) (84.3%). Most common barriers were finding the Internet not interesting (28.3%) or too difficult (27.9%), as well as security concerns (22.1% to 24.3%). Using the Internet a lot (vs just a bit or not at all) during the pandemic was associated with younger age (Adj ORs = 4.76 - 6.39, Ps < .001), having a diagnosis of bipolar disorder (compared to psychosis; Adj OR = 3.88, P < .001), or reporting a decline in mental health (compared to no decline; Adj OR = 1.92, P = .01). ConclusionMost people with SMI were limited or non-users of the Internet during the pandemic, which seems to be mainly attributable to lack of interest and skills, rather than lack of devices or connectivity. Older adults with psychosis should be the focus of interventions to support digital engagement in people with SMI.
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SARS-CoV-2 therapeutic antibody discovery efforts have met with notable success but have been associated with a generally inefficient process, requiring the production and characterization of exceptionally large numbers of candidates for the identification of a small set of leads. Here, we show that incorporating antibody-ligand blocking as part of LIBRA-seq, the high-throughput sequencing platform for antibody discovery, results in efficient identification of ultra-potent neutralizing antibodies against SARS-CoV-2. LIBRA-seq with ligand blocking is a general platform for functional antibody discovery targeting the disruption of antigen-ligand interactions.
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AimsTo explore: how satisfied people with severe mental illness (SMI) are with the support received during the pandemic; understand any difficulties encountered when accessing both mental health and primary care services; consider ways to mitigate these difficulties; and assess the perceived need for future support from mental health services. Materials and MethodsA representative sample was drawn from a large transdiagnostic clinical cohort of people with SMI, which was recruited between April 2016 and March 2020. The sample was re-surveyed a few months after the beginning of the restrictions. Descriptive frequency statistics were used to analyse the quantitative data. The free text responses were analysed thematically. Results367 participants responded to the survey. Two thirds were receiving support from mental health services with the rest supported in primary care or self-managing. A quarter thought they would need more mental health support in the coming year. Half had needed to used community mental health services during the pandemic and the majority had been able to get support. A minority reported that their mental health had deteriorated but they had either not got the supported they wanted or had not sought help. The biggest service change was the reduction in face-to-face appointments and increasing use of phone and video call support. Nearly half of those using mental health services found this change acceptable or even preferred it; acceptability was influenced by several factors. Participants were more likely to be satisfied with support received when seen in person. DiscussionAlthough most participants were satisfied with the mental health support they had received, a minority were not. This, couple with findings on future need for mental health support has implications for post pandemic demand on services. Remote care has brought benefits but also risks that it could increase inequalities in access to services.
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BackgroundAGILE is a phase Ib/IIa platform for rapidly evaluating COVID-19 treatments. In this trial (NCT04746183) we evaluated the safety and optimal dose of molnupiravir in participants with early symptomatic infection. MethodsWe undertook a dose-escalating, open-label, randomised-controlled (standard-of-care) Bayesian adaptive phase I trial at the Royal Liverpool and Broadgreen Clinical Research Facility. Participants (adult outpatients with PCR-confirmed SARS-CoV-2 infection within 5 days of symptom onset) were randomised 2:1 in groups of 6 participants to 300mg, 600mg and 800mg doses of molnupiravir orally, twice daily for 5 days or control. A dose was judged unsafe if the probability of 30% or greater dose-limiting toxicity (the primary outcome) over controls was higher than 25%. Secondary outcomes included safety, clinical progression, pharmacokinetics and virologic responses. ResultsOf 103 volunteers screened, 18 participants were enrolled between 17 July and 30 October 2020. Molnupiravir was well tolerated at 400, 600 or 800mg doses with no serious or severe adverse events. Overall, 4 of 4 (100%), 4 of 4 (100%) and 1 of 4 (25%) of the participants receiving 300, 600 and 800mg molnupiravir respectively, and 5 of 6 (83%) controls, had at least one adverse event, all of which were mild ([≤]grade 2). The probability of [≥]30% excess toxicity over controls at 800mg was estimated at 0.9%. ConclusionMolnupiravir was safe and well tolerated; a dose of 800mg twice-daily for 5 days was recommended for Phase II evaluation.
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BackgroundPeople with severe mental ill health (SMI) experience a mortality gap of 15-20 years. COVID-19 has amplified population health inequalities, and there is concern that people with SMI will be disproportionately affected. Understanding how health risk behaviours have changed during the pandemic is important when developing strategies to mitigate future increases in health inequalities. MethodsWe sampled from an existing cohort of people with SMI. Researchers contacted participants by phone or post to invite them to take part in a survey about how the pandemic had affected them. We asked people about their health risk behaviours and how these had changed during the pandemic. We created an index of changed behaviours, comprising dietary factors, smoking, lack of exercise, and drinking patterns. By creating data linkages, we compared their responses during pandemic restrictions to responses they gave prior to the pandemic. Outcomes367 people provided health risk data. 47.5% of participants reported taking less physical activity during the pandemic and of those who smoke 54.5% reported smoking more heavily. Self-reported deterioration in physical health and younger age were significantly associated with an increase in health risk behaviours (adjusted OR for physical health 1.59, 95%CI 1.22-2.07; adjusted OR for Age 0.99, 95%CI 0.98-1.00). InterpretationCOVID-19 is likely to amplify health inequalities for people with SMI. Health services should target health risk behaviours for people with SMI to mitigate the immediate and long lasting impacts of the COVID-19 pandemic. FundingMedical Research council, Yorkshire and Humber Applied Research Collaboration, Wellcome and UKRI.
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Smoking rates are higher for people who use mental health services which contributes substantially to health inequalities. Smoking can lead to worse COVID-19 outcomes, yet it remains unclear whether smoking has changed for people who use mental health services. We examined smoking patterns in a large clinical cohort of people with SMI before and during the pandemic. We found high levels of nicotine dependence and heavier patterns of smoking. Whilst some people had reported quitting, it is likely that smoking inequalities have become further entrenched. Mental health services should seek to mitigate this modifiable risk and source of poor health.