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1.
Addict Sci Clin Pract ; 18(1): 39, 2023 06 02.
Artigo em Inglês | MEDLINE | ID: covidwho-20235217

RESUMO

BACKGROUND: Breaking Free Online (BFO), a computer-assisted therapy (CAT) program for substance use disorders (SUD), has been available across UK treatment services for the past decade and has demonstrated efficacy. The Covid-19 pandemic has contributed to digital and 'telehealth' approaches to healthcare delivery becoming more common and accepted, and has in parallel, increased numbers of referrals to SUD services because of the impact pandemic-related stress has had on substance using habits in the general population. Digital and telehealth approaches, such as BFO, have the potential to support the treatment system to meet this increased demand for SUD services. METHODS: Parallel-group randomized controlled trial of eight-week BFO as an adjunct to standard treatment for SUD, in comparison to standard treatment only, at a National Health Service (NHS) Mental Health Trust in North-West England. Participants will be service users aged 18 years and over with demonstrable SUD for at least 12-months. Interventional and control groups will be compared on multiple measures from baseline to post-treatment assessment at eight-weeks, and then three and six-months follow-up. Primary outcome will be self-reported substance use, with secondary outcomes being standardized assessments of substance dependence, mental health, biopsychosocial functioning and quality of life. DISCUSSION: This study will examine whether BFO and telehealth support, when delivered as an adjunct to standard SUD interventions, improves outcomes for services users receiving NHS SUD treatment. Findings from the study will be used to inform both developments to the BFO program and guidance around augmenting the delivery of CAT programs via telehealth. Trial registration registered with ISRCTN on 25th May 2021-registration number: 13694016. PROTOCOL VERSION: 3.0 05th April 2022. TRIAL STATUS: This trial is currently open to recruitment-estimated to be completed in May 2023.


Assuntos
COVID-19 , Transtornos Relacionados ao Uso de Substâncias , Terapia Assistida por Computador , Humanos , Pandemias , Qualidade de Vida , Medicina Estatal , Terapia Assistida por Computador/métodos , Transtornos Relacionados ao Uso de Substâncias/terapia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
BMJ Open ; 13(4): e071024, 2023 04 19.
Artigo em Inglês | MEDLINE | ID: covidwho-2300325

RESUMO

OBJECTIVES: Liverpool has high prevalence of alcohol use disorders (AUDs) compared with the rest of the UK. Early identification and referral in primary care would improve treatment for people with AUD. This study aimed to identify changes in prevalence and incidence of AUD in primary care in Liverpool, to identify local need for specialist services. DESIGN: Cross-sectional retrospective analysis of electronic health records. SETTING: National Health Service (NHS) Liverpool Clinical Commissioning Group (CCG) primary care. In total, 62 of the 86 general practitioner (GP) practices agreed to share their anonymised Egton Medical Information Systems (EMIS) data from 1 January 2017 to 31 December 2021. PARTICIPANTS: Patients aged over 18 years with a SNOMED code for alcohol dependence (AD) or hazardous drinking (N=4936). Patients were excluded if they had requested that their data was not to be shared, and practices were excluded if they opted out (N=2) or did not respond to the data sharing request (N=22). PRIMARY AND SECONDARY OUTCOMES: Prevalence and incidence of AUD diagnoses in primary care over the 5-year period; demographic profile of patients (sex, age, ethnicity, occupation); GP postcode; alcohol-related medications; and psychiatric and physical comorbidities. RESULTS: There were significant decreases in incidence of AD and hazardous drinking diagnoses over the 5 years (p<0.001 in all cases). Prevalence showed less change over time. Diagnoses were significantly higher in more deprived areas (Indices of Multiple Deprivation decile 1 vs 2-10). Overall pharmacotherapy prescriptions were lower than national estimates. CONCLUSIONS: There are low levels of identification of AUDs in primary care in Liverpool, and this is decreasing year on year. There was weak evidence to suggest patients in the most deprived areas are less likely to receive pharmacotherapy once diagnosed. Future research should seek to investigate practitioner and patient perspectives on barriers and facilitators to management of AUDs in primary care.


Assuntos
Alcoolismo , Humanos , Adulto , Pessoa de Meia-Idade , Alcoolismo/diagnóstico , Alcoolismo/epidemiologia , Alcoolismo/tratamento farmacológico , Prevalência , Incidência , Estudos Retrospectivos , Estudos Transversais , Medicina Estatal , Atenção Primária à Saúde , Reino Unido/epidemiologia
3.
JMIR Form Res ; 7: e40518, 2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: covidwho-2278463

RESUMO

BACKGROUND: It is unclear whether heavy alcohol use and associated hangover symptoms changed as a result of the COVID-19 pandemic. Due to a lack of available accurate and nonretrospective self-reported data, it is difficult to directly assess hangover symptoms during the COVID-19 pandemic. OBJECTIVE: This study aimed to examine whether alcohol-induced hangover-related internet searches (eg, "how to cure a hangover?") increased, decreased, or remained the same in England before versus during the COVID-19 pandemic (2020-2021) and during periods of national lockdown. Secondary aims were to examine if hangover-related internet searches in England differed compared to a country that did not impose similar COVID-19 lockdown restrictions. METHODS: Using historical data from Google Trends for England, we compared the relative search volume (RSV) of hangover-related searches in the years before (2016-2019) versus during the COVID-19 pandemic (2020-2021), as well as in periods of national lockdown versus the same periods in 2016-2019. We also compared the RSV of hangover-related searches during the same time frames in a European country that did not introduce national COVID-19 lockdowns at the beginning of the pandemic (Sweden). Hangover-related search terms were identified through consultation with a panel of alcohol researchers and a sample from the general public. Statistical analyses were preregistered prior to data collection. RESULTS: There was no overall significant difference in the RSV of hangover-related terms in England during 2016-2019 versus 2020-2021 (P=.10; robust d=0.02, 95% CI 0.00-0.03). However, during national lockdowns, searches for hangover-related terms were lower, particularly during the first national lockdown in England (P<.001; d=.19, 95% CI 0.16-0.24; a 44% relative decrease). In a comparison country that did not introduce a national lockdown in the early stages of the pandemic (Sweden), there was no significant decrease in hangover-related searches during the same time period (P=.06). However, across both England and Sweden, during later periods of COVID-19 restrictions in 2020 and 2021, the RSV of hangover-related terms was lower than that in the same periods during 2016-2019. Exploratory analyses revealed that national monthly variation in alcohol sales both before and during the COVID-19 pandemic were positively correlated with the frequency of hangover-related searches, suggesting that changes in hangover-related searches may act as a proxy for changes in alcohol consumption. CONCLUSIONS: Hangover-related internet searches did not differ before versus during the COVID-19 pandemic in England but did reduce during periods of national lockdown. Further research is required to confirm how changes in hangover-related search volume relate to heavy episodic alcohol use. TRIAL REGISTRATION: Open Science Framework 2Y86E; https://osf.io/2Y86E.

4.
Thorax ; 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: covidwho-2264899
5.
BMC Public Health ; 21(1): 2110, 2021 11 17.
Artigo em Inglês | MEDLINE | ID: covidwho-1516554

RESUMO

BACKGROUND: The coronavirus (COVID-19) pandemic has highlighted that individuals with behavioural risk factors commonly associated with non-communicable diseases (NCDs), such as smoking, harmful alcohol use, obesity, and physical inactivity, are more likely to experience severe symptoms from COVID-19. These risk factors have been shown to increase the risk of NCDs, but less is known about their broader influence on communicable diseases. Taking a wide focus on a range of common communicable diseases, this review aimed to synthesise research examining the impact of behavioural risk factors commonly associated with NCDs on risks of contracting, or having more severe outcomes from, communicable diseases. METHODS: Literature searches identified systematic reviews and meta-analyses that examined the association between behavioural risk factors (alcohol, smoking, illicit drug use, physical inactivity, obesity and poor diet) and the contraction/severity of common communicable diseases, including infection or associated pathogens. An a priori, prospectively registered protocol was followed (PROSPERO; registration number CRD42020223890). RESULTS: Fifty-three systematic reviews were included, of which 36 were also meta-analyses. Reviews focused on: tuberculosis, human immunodeficiency virus, hepatitis C virus, hepatitis B virus, invasive bacterial diseases, pneumonia, influenza, and COVID-19. Twenty-one reviews examined the association between behavioural risk factors and communicable disease contraction and 35 examined their association with communicable disease outcomes (three examined their association with both contraction and outcomes). Fifty out of 53 reviews (94%) concluded that at least one of the behavioural risk factors studied increased the risk of contracting or experiencing worse health outcomes from a communicable disease. Across all reviews, effect sizes, where calculated, ranged from 0.83 to 8.22. CONCLUSIONS: Behavioural risk factors play a significant role in the risk of contracting and experiencing more severe outcomes from communicable diseases. Prevention of communicable diseases is likely to be most successful if it involves the prevention of behavioural risk factors commonly associated with NCDs. These findings are important for understanding risks associated with communicable disease, and timely, given the COVID-19 pandemic and the need for improvements in future pandemic preparedness. Addressing behavioural risk factors should be an important part of work to build resilience against any emerging and future epidemics and pandemics.


Assuntos
COVID-19 , Doenças Transmissíveis , Doenças Transmissíveis/epidemiologia , Humanos , Pandemias , Fatores de Risco , SARS-CoV-2
6.
Curr Opin Pulm Med ; 28(6): 571-576, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: covidwho-2029136

RESUMO

PURPOSE OF REVIEW: This article reviews the impact of some of the most recent changes in clinical care management in cystic fibrosis on infection prevention practice and advice for people with cystic fibrosis. RECENT FINDINGS: People with cystic fibrosis (CF) consistently highlight infection control as one of their major concerns. Infection prevention guidance and practice has facilitated successful decreases in rates of many transmissible CF pathogens. The coronavirus disease 2019 pandemic highlighted the clinical significance of respiratory viral infections and has accelerated the implementation of remote monitoring and telemedicine consultations as standard practice in CF. The continued improvement in health of the CF population is being further augmented by the introduction of new therapies, in particular cystic fibrosis transmembrane conductance regulator modulators. Infection prevention will remain pertinent to CF care, but these recent changes in clinical practice will have ongoing implications for infection prevention guidance in CF. SUMMARY: Recent changes in CF clinical care have implications that will lead to further evolution of infection control practice and advice.


Assuntos
COVID-19 , Fibrose Cística , Fibrose Cística/tratamento farmacológico , Fibrose Cística/terapia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Humanos , Controle de Infecções , Mutação , Pandemias/prevenção & controle
7.
Health Justice ; 10(1): 28, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: covidwho-2009474

RESUMO

BACKGROUND: Methamphetamine use can be associated with involvement with correctional services and incarceration. Traditionally, treatments for methamphetamine use have been delivered in-person - however, lockdowns initiated during the COVID-19 pandemic significantly reduced access to such in-person support in prisons. Therefore, in May 2020 a digital cognitive-behavioral therapy (CBT) program for substance use disorders - 'Breaking Free from Substance Abuse' - was made available across prisons in Ohio in order to meet this treatment gap. This represents the first time this digital CBT intervention has been made widely available to incarcerated people residing in prisons or jails in the United States (US). This was a within-subjects study using data from 2187 Ohio prison residents who engaged with this digital CBT program to address their methamphetamine use. RESULTS: Participants reported multiple psychosocial risk factors, including moderate to severe substance dependence, depression and anxiety; interpersonal conflict; aggressive behavior; paranoia; and difficulties with work, education and accommodation. Significant reductions in substance dependence, depression/anxiety and biopsychosocial impairment, and improvements in quality of life, were identified in the sample. Risk factors were associated with less positive outcomes, specifically interpersonal conflict and poor mental health. Completion of specific components of the program were associated with more positive outcomes - a dose response was also identified. CONCLUSIONS: Digital CBT can be delivered in secure US correctional settings and may help to fill unmet needs for in-person treatment. Specifically, this digital CBT program may support incarcerated individuals to address methamphetamine use, with outcomes being associated with psychosocial risk factors and program engagement.

8.
J Vasc Surg ; 76(5): 1398-1404.e4, 2022 11.
Artigo em Inglês | MEDLINE | ID: covidwho-1907528

RESUMO

OBJECTIVE: The onset of the COVID-19 (coronavirus disease 2019) pandemic mandated postponement of the in-person Vascular Surgery Board 2020 certifying examination (CE). Vascular surgery virtual CEs (VVCEs) were developed for the scheduled 2020 CEs (rescheduled to January 2021) and 2021 CEs (rescheduled to July 2021) to avoid postponing the certification testing. In the present study, we have reported the development, implementation, and outcomes of the first two VVCEs. METHODS: The VVCE was similar to the in-person format (three 30-minutes sessions, two examiners, four questions) but required a proctor and a host. In contrast to the general surgery VCEs, the VVCE also incorporated images. The candidates and examiners were instructed on the format, and technology checks were performed before the VVCE. The candidates were given the opportunity to invalidate their examination for technology-related reasons immediately after the examination. Postexamination surveys were administered to all the participants. RESULTS: The VVCEs were completed by 356 of 357 candidates (99.7%). The pass rates for the January 2021 and July 2021 examinations were 97.6% (first time, 99.4%; retake, 70%) and 94.7% (first time, 94.6%; retake, 100%), respectively. The pass rates were not significantly different from the 2019 in-person CE (χ2 = 2.30; P = .13; and χ2 = 0.01; P = .91, for the January 2021 and July 2021 examinations, respectively). None of the candidates had invalidated their examination. The candidates (162 of 356; 46%), examiners (64 of 118; 54%), proctors (25 of 27; 93%), and hosts (8 of 9; 89%) completing the survey were very satisfied with the examination (Likert score 4 or 5: candidates, 92.6%; noncandidates, 96.9%) and found the technology domains (Zoom, audio, video, viewing images) to be very good (Likert score 4 or 5), with candidate and other responder scores of 73% to 84% and >94%, respectively. Significantly more of the candidates had favored a future VVCE compared with the examiners (87% vs 32%; χ2 = 67.1; P < .001). The free text responses from all responders had commented favorably on the organization and implementation of the examination. However, some candidates had expressed concerns about image sizes, and some examiners had expressed concern about the time constraints for the question format. The candidates appreciated the convenience of an at-home examination, especially the avoidance of travel costs. CONCLUSIONS: The two Vascular Surgery Board VCEs were shown to be psychometrically sound and were overwhelmingly successful, demonstrating that image-based virtual examinations are feasible and could become the standard for the future.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Certificação , Procedimentos Cirúrgicos Vasculares , Inquéritos e Questionários
9.
Frontiers in psychiatry ; 13, 2022.
Artigo em Inglês | EuropePMC | ID: covidwho-1887692

RESUMO

Background Peoples' sexual behaviors have changed during the period of enforced COVID-19 social distancing, in some cases, to cope with negative feelings during lockdown. Research on coping using sex is relatively restricted to samples of men with a history of sexual offending, and it is unknown whether coping using sex is associated with health-related behaviors and mental health in the general population. Aim We examined if coping using sex before and during lockdown was associated with adverse outcomes (i.e., self-perceived reduction in health-related behaviors and mental health) in a community sample. Hypotheses We hypothesized that participants who reported greater use of sex to cope in the weeks preceding lockdown would show a greater decline in health-related behaviors and mental health during lockdown. Furthermore, that changes in coping using sex resulting from lockdown would account for further variance in the worsening of health-related behaviors and mental health. Methods Participants were UK residents, aged 18–60 years, and fluent in English. 789 participants completed an online survey, providing demographic information, self-reported social distancing, loneliness, and coping using sex over a 14-day period during lockdown, and retrospectively preceding lockdown. Outcomes Participants reported perceived changes in health-related behaviors and mental health symptomatology during lockdown compared to before the pandemic. They also self-reported levels of stress, anxiety and depression during lockdown. Results Greater coping using sex prior to lockdown predicted positive change in health-related behaviors, for example, higher scores were associated with participants reporting having exercised and slept more. It was also associated with higher trait levels of anxiety, stress and depression during lockdown. Changes in coping using sex from before to during lockdown did not predict perceived changes in health related behaviors or mental health symptomatology. Conclusions Overall, greater coping using sex prior to lockdown was associated with worse mental health symptomatology during lockdown (anxiety, depression and stress), however, it was also associated with perceived positive change in health-related behaviors compared with before lockdown. This suggests that coping using sex may be associated with negative emotional reactions during lockdown, but may also be linked with positive change in health-promoting behaviors.

10.
Health Econ ; 31(5): 912-920, 2022 05.
Artigo em Inglês | MEDLINE | ID: covidwho-1680331

RESUMO

This paper extends earlier on socioeconomic inequality in mental health, measured by the General Health Questionnaire, to include the second national lockdown up to March 2021.


Assuntos
COVID-19 , Angústia Psicológica , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Humanos , Pandemias , SARS-CoV-2 , Fatores Socioeconômicos , Reino Unido/epidemiologia
11.
BMJ Open ; 12(1): e053327, 2022 01 17.
Artigo em Inglês | MEDLINE | ID: covidwho-1627515

RESUMO

OBJECTIVE: To identify the key individual-level (demographics, attitudes, mobility) and contextual (COVID-19 case numbers, tiers of mobility restrictions, urban districts) determinants of adopting the NHS COVID-19 contact tracing app and continued use overtime. DESIGN AND SETTING: A three-wave panel survey conducted in England in July 2020 (background survey), November 2020 (first measure of app adoption) and March 2021 (continued use of app and new adopters) linked with official data. PARTICIPANTS: N=2500 adults living in England, representative of England's population in terms of regional distribution, age and gender (2011 census). PRIMARY OUTCOME: Repeated measures of self-reported app usage. ANALYTICAL APPROACH: Multilevel logistic regression linking a range of individual level (from survey) and contextual (from linked data) determinants to app usage. RESULTS: We observe initial app uptake at 41%, 95% CI (0.39% to 0.43%), and a 12% drop-out rate by March 2021, 95% CI (0.10% to 0.14%). We also found that 7% of nonusers as of wave 2 became new adopters by wave 3, 95% CI (0.05% to 0.08%). Initial uptake (or failure to use) of the app associated with social norms, privacy concerns and misinformation about third-party data access, with those living in postal districts with restrictions on mobility less likely to use the app. Perceived lack of transparent evidence of effectiveness was associated with drop-out of use. In addition, those who trusted the government were more likely to adopt in wave 3 as new adopters. CONCLUSIONS: Successful uptake of the contact tracing app should be evaluated within the wider context of the UK Government's response to the crisis. Trust in government is key to adoption of the app in wave 3 while continued use is linked to perceptions of transparent evidence. Providing clear information to address privacy concerns could increase uptake, however, the disparities in continued use among ethnic minority participants needs further investigation.


Assuntos
COVID-19 , Aplicativos Móveis , Adulto , Busca de Comunicante , Minorias Étnicas e Raciais , Etnicidade , Humanos , Grupos Minoritários , SARS-CoV-2 , Web Semântica
12.
Aust Health Rev ; 46(3): 279-283, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: covidwho-1562010

RESUMO

Digital disruption and transformation of health care is occurring rapidly. Concurrently, a global syndemic of preventable chronic disease is crippling healthcare systems and accelerating the effect of the COVID-19 pandemic. Healthcare investment is paradoxical; it prioritises disease treatment over prevention. This is an inefficient break-fix model versus a person-centred predict-prevent model. It is easy to reward and invest in acute health systems because activity is easily measured and therefore funded. Social, environmental and behavioural health determinants explain ~70% of health variance; yet, we cannot measure these community data contemporaneously or at population scale. The dawn of digital health and the digital citizen can initiate a precision prevention era, where consumer-centred, real-time data enables a new ability to count and fund population health, making disease prevention 'matter'. Then, precision decision making, intervention and policy to target preventable chronic disease (e.g. obesity) can be realised. We argue for, identify barriers to, and propose three horizons for digital health transformation of population health towards precision prevention of chronic disease, demonstrating childhood obesity as a use case. Clinicians, researchers and policymakers can commence strategic planning and investment for precision prevention of chronic disease to advance a mature, value-based model that will ensure healthcare sustainability in Australia and globally.


Assuntos
COVID-19 , Obesidade Infantil , COVID-19/prevenção & controle , Criança , Atenção à Saúde , Instalações de Saúde , Humanos , Pandemias/prevenção & controle
14.
J Affect Disord ; 296: 567-576, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: covidwho-1446777

RESUMO

BACKGROUND: Increases in mental health problems have been observed during the COVID-19 pandemic. The objectives were to examine the extent to which mental health symptoms changed during the pandemic in 2020, whether changes were persistent or short lived, and if changes were symptom specific. METHODS: Systematic review and meta-analysis of longitudinal cohort studies examining changes in mental health among the same group of participants before vs. during the pandemic in 2020. RESULTS: Sixty-five studies were included. Compared to pre-pandemic outbreak, there was an overall increase in mental health symptoms observed during March-April 2020 (SMC = .102 [95% CI: .026 to .192]) that significantly declined over time and became non-significant (May-July SMC = .067 [95% CI: -.022 to .157]. Compared to measures of anxiety (SMC = 0.13, p = 0.02) and general mental health (SMC = -.03, p = 0.65), increases in depression and mood disorder symptoms tended to be larger and remained significantly elevated in May-July [0.20, 95% CI: .099 to .302]. In primary analyses increases were most pronounced among samples with physical health conditions and there was no evidence of any change in symptoms among samples with a pre-existing mental health condition. LIMITATIONS: There was a high degree of unexplained heterogeneity observed (I2s > 90%), indicating that change in mental health was highly variable across samples. CONCLUSIONS: There was a small increase in mental health symptoms soon after the outbreak of the COVID-19 pandemic that decreased and was comparable to pre-pandemic levels by mid-2020 among most population sub-groups and symptom types.


Assuntos
COVID-19 , Pandemias , Ansiedade , Estudos de Coortes , Depressão , Humanos , Estudos Longitudinais , Saúde Mental , SARS-CoV-2
15.
MIS Quarterly ; 45(3):iii-xvi, 2021.
Artigo em Inglês | Academic Search Complete | ID: covidwho-1436707

RESUMO

An editorial on emotions and information science research in light of the COVID-19 pandemic is presented. The authors discuss the need to better express emotions, the need for emotional awareness in the development of resiliency and better mental health, and how this can be reflected in information science research and the "MIS Quarterly."

16.
Nat Commun ; 12(1): 5553, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: covidwho-1434104

RESUMO

SARS-CoV-2 is the causative agent behind the COVID-19 pandemic, responsible for over 170 million infections, and over 3.7 million deaths worldwide. Efforts to test, treat and vaccinate against this pathogen all benefit from an improved understanding of the basic biology of SARS-CoV-2. Both viral and cellular proteases play a crucial role in SARS-CoV-2 replication. Here, we study proteolytic cleavage of viral and cellular proteins in two cell line models of SARS-CoV-2 replication using mass spectrometry to identify protein neo-N-termini generated through protease activity. We identify previously unknown cleavage sites in multiple viral proteins, including major antigens S and N: the main targets for vaccine and antibody testing efforts. We discover significant increases in cellular cleavage events consistent with cleavage by SARS-CoV-2 main protease, and identify 14 potential high-confidence substrates of the main and papain-like proteases. We show that siRNA depletion of these cellular proteins inhibits SARS-CoV-2 replication, and that drugs targeting two of these proteins: the tyrosine kinase SRC and Ser/Thr kinase MYLK, show a dose-dependent reduction in SARS-CoV-2 titres. Overall, our study provides a powerful resource to understand proteolysis in the context of viral infection, and to inform the development of targeted strategies to inhibit SARS-CoV-2 and treat COVID-19.


Assuntos
Antivirais/farmacologia , COVID-19/metabolismo , Inibidores de Proteases/farmacologia , SARS-CoV-2/efeitos dos fármacos , Animais , Linhagem Celular , Dipeptídeos/farmacologia , Humanos , Mutação , Quinase de Cadeia Leve de Miosina/antagonistas & inibidores , Quinase de Cadeia Leve de Miosina/genética , Quinase de Cadeia Leve de Miosina/metabolismo , Proteólise , Proteômica , RNA Interferente Pequeno/farmacologia , SARS-CoV-2/genética , Proteases Virais/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismo , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Quinases da Família src/antagonistas & inibidores , Quinases da Família src/genética , Quinases da Família src/metabolismo , Tratamento Farmacológico da COVID-19
17.
Nature ; 599(7885): 465-470, 2021 11.
Artigo em Inglês | MEDLINE | ID: covidwho-1428880

RESUMO

Monoclonal antibodies with neutralizing activity against SARS-CoV-2 have demonstrated clinical benefits in cases of mild-to-moderate SARS-CoV-2 infection, substantially reducing the risk for hospitalization and severe disease1-4. Treatment generally requires the administration of high doses of these monoclonal antibodies and has limited efficacy in preventing disease complications or mortality among hospitalized patients with COVID-195. Here we report the development and evaluation of anti-SARS-CoV-2 monoclonal antibodies with optimized Fc domains that show superior potency for prevention or treatment of COVID-19. Using several animal disease models of COVID-196,7, we demonstrate that selective engagement of activating Fcγ receptors results in improved efficacy in both preventing and treating disease-induced weight loss and mortality, significantly reducing the dose required to confer full protection against SARS-CoV-2 challenge and for treatment of pre-infected animals. Our results highlight the importance of Fcγ receptor pathways in driving antibody-mediated antiviral immunity and exclude the possibility of pathogenic or disease-enhancing effects of Fcγ receptor engagement of anti-SARS-CoV-2 antibodies upon infection. These findings have important implications for the development of Fc-engineered monoclonal antibodies with optimal Fc-effector function and improved clinical efficacy against COVID-19 disease.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Tratamento Farmacológico da COVID-19 , COVID-19/imunologia , Fragmentos Fc das Imunoglobulinas/imunologia , Fragmentos Fc das Imunoglobulinas/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/imunologia , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/farmacologia , Anticorpos Neutralizantes/uso terapêutico , Cricetinae , Modelos Animais de Doenças , Feminino , Humanos , Fragmentos Fc das Imunoglobulinas/química , Fragmentos Fc das Imunoglobulinas/farmacologia , Imunoglobulina G/química , Imunoglobulina G/imunologia , Masculino , Camundongos , Profilaxia Pré-Exposição , Receptores de IgG/química , Receptores de IgG/imunologia , Resultado do Tratamento
19.
Drug Alcohol Depend ; 226: 108913, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: covidwho-1322069

RESUMO

BACKGROUND: Coronavirus (COVID-19) resulted in lockdown measures in the UK, which has impacted alcohol use. Alcohol is often used as a coping mechanism and there are public health concerns regarding excessive consumption due to the pandemic. We aimed to longitudinally assess drinking behaviors, and associated factors, during the first UK government-mandated lockdown. METHODS: An online survey was distributed through social media (8th April 2020, onwards). Fortnightly follow up surveys were emailed to participants. The primary outcome measure was 'weekly unit consumption' and data was collected on a range of potentially related factors: demographics, factors relating to COVID-19 (e.g., health, work status), drinking motives, context of drinking, drinking intentions, mood, depression and anxiety. FINDINGS: A total of 539 self-selected participants completed the baseline survey, with 186 completing at least 3 follow up surveys for multilevel modelling analysis. Personal coping motives, anxiety, drinking at home alone, and drinking at home with others were positively associated with alcohol consumption during lockdown. The following baseline measures also predicted increased consumption: male gender, lower education, and higher AUDIT scores (based on behavior prior to lockdown). Findings were consistent when utilizing an inverse probability weight to account for predictors of attrition (female, younger age, higher baseline AUDIT scores). CONCLUSIONS: Those already drinking at hazardous levels were more likely to increase their consumption, as were those who were drinking to cope. As we recover from the pandemic, there is a need for widespread alcohol support, and certain groups may need targeted support.


Assuntos
COVID-19 , Saúde Mental , Adaptação Psicológica , Consumo de Bebidas Alcoólicas/epidemiologia , Controle de Doenças Transmissíveis , Feminino , Humanos , Masculino , Motivação , SARS-CoV-2
20.
Crit Care ; 25(1): 226, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: covidwho-1286048

RESUMO

BACKGROUND: Rapid response systems aim to achieve a timely response to the deteriorating patient; however, the existing literature varies on whether timing of escalation directly affects patient outcomes. Prior studies have been limited to using 'decision to admit' to critical care, or arrival in the emergency department as 'time zero', rather than the onset of physiological deterioration. The aim of this study is to establish if duration of abnormal physiology prior to critical care admission ['Score to Door' (STD) time] impacts on patient outcomes. METHODS: A retrospective cross-sectional analysis of data from pooled electronic medical records from a multi-site academic hospital was performed. All unplanned adult admissions to critical care from the ward with persistent physiological derangement [defined as sustained high National Early Warning Score (NEWS) > / = 7 that did not decrease below 5] were eligible for inclusion. The primary outcome was critical care mortality. Secondary outcomes were length of critical care admission and hospital mortality. The impact of STD time was adjusted for patient factors (demographics, sickness severity, frailty, and co-morbidity) and logistic factors (timing of high NEWS, and out of hours status) utilising logistic and linear regression models. RESULTS: Six hundred and thirty-two patients were included over the 4-year study period, 16.3% died in critical care. STD time demonstrated a small but significant association with critical care mortality [adjusted odds ratio of 1.02 (95% CI 1.0-1.04, p = 0.01)]. It was also associated with hospital mortality (adjusted OR 1.02, 95% CI 1.0-1.04, p = 0.026), and critical care length of stay. Each hour from onset of physiological derangement increased critical care length of stay by 1.2%. STD time was influenced by the initial NEWS, but not by logistic factors such as out-of-hours status, or pre-existing patient factors such as co-morbidity or frailty. CONCLUSION: In a strictly defined population of high NEWS patients, the time from onset of sustained physiological derangement to critical care admission was associated with increased critical care and hospital mortality. If corroborated in further studies, this cohort definition could be utilised alongside the 'Score to Door' concept as a clinical indicator within rapid response systems.


Assuntos
Deterioração Clínica , Administração Hospitalar/estatística & dados numéricos , Mortalidade/tendências , Tempo para o Tratamento/normas , Idoso , Estudos Transversais , Feminino , Administração Hospitalar/normas , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Análise de Regressão , Estudos Retrospectivos , Medição de Risco/métodos , Medição de Risco/normas , Medição de Risco/estatística & dados numéricos , Tempo para o Tratamento/estatística & dados numéricos
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