Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 11 de 11
Filter
1.
Epidemiol Psychiatr Sci ; 31: e48, 2022 Jul 11.
Article in English | MEDLINE | ID: covidwho-1931281

ABSTRACT

AIMS: The mounting evidence for effective delivery of psychological interventions by non-specialists in low- and middle-income settings has led to a rapid expansion of mental health and psychosocial support trainings globally. As such, there is a demand for strategies on how to train and implement these services to attain adequate quality. This study aims to evaluate the added value of a competency-driven approach to training of facilitators for a group intervention for children with severe emotional distress in Lebanon. METHODS: In a controlled before and after study, 24 trainees were randomly allocated to participate in either a competency-driven training (CDT) or training-as-usual (TAU) (1 : 1) for a psychological intervention for children with severe emotional distress. We assessed the change in demonstrated competencies, using standardised role-plays, before and after the training. Measures included the 13-item Working with children-Assessment of Competencies Tool (WeACT), the 15-item ENhancing Assessment of Common Therapeutic factors (ENACT) and the 6-item Group facilitation: Assessment of Competencies Tool (GroupACT). The trainer in the experimental arm used pre-training and during training competency assessment scores to make real-time adjustment to training delivery. Due to COVID-19 pandemic restrictions, all activities were done remotely. RESULTS: CDT resulted in significantly better outcomes on increasing competencies on the WeACT (repeated measures analysis of variance; F(1, 22) = 6.49, p < 0.018) and on the GroupACT (Mann-Whitney U = 22, p < 0.003), though not statistically significant on the ENACT. There is no significant between-group difference on the reduction of harmful behaviours, mainly because both forms of training appear equally successful in eliminating such behaviours. CONCLUSIONS: This proof-of-concept study demonstrates the potential of CDT, using standardised assessment of trainee competencies, to contribute to better training outcomes without extending the duration of training. CDT can result in up to 18% greater increase in adequate competency, when compared to TAU. The study also yields recommendations for further enhancing the benefits of competency-driven strategies. A fully powered trial is needed to confirm these findings.


Subject(s)
COVID-19 , Psychosocial Intervention , Child , Humans , Lebanon , Mental Health , Pandemics
2.
PubMed; 2022.
Preprint in English | PubMed | ID: ppcovidwho-338334

ABSTRACT

Infectious diseases have shaped the human population genetic structure, and genetic variation influences the susceptibility to many viral diseases. However, a variety of challenges have made the implementation of traditional human Genome-wide Association Studies (GWAS) approaches to study these infectious outcomes challenging. In contrast, mouse models of infectious diseases provide an experimental control and precision, which facilitates analyses and mechanistic studies of the role of genetic variation on infection. Here we use a genetic mapping cross between two distinct Collaborative Cross mouse strains with respect to SARS-CoV disease outcomes. We find several loci control differential disease outcome for a variety of traits in the context of SARS-CoV infection. Importantly, we identify a locus on mouse Chromosome 9 that shows conserved synteny with a human GWAS locus for SARS-CoV-2 severe disease. We follow-up and confirm a role for this locus, and identify two candidate genes, CCR9 and CXCR6 that both play a key role in regulating the severity of SARS-CoV, SARS-CoV-2 and a distantly related bat sarbecovirus disease outcomes. As such we provide a template for using experimental mouse crosses to identify and characterize multitrait loci that regulate pathogenic infectious outcomes across species.

3.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-334706

ABSTRACT

The COVID-19 pandemic remains uncontrolled despite the rapid rollout of safe and effective SARS-CoV-2 vaccines, underscoring the need to develop highly effective antivirals. In the setting of waning immunity from infection and vaccination, breakthrough infections are becoming increasingly common and treatment options remain limited. Additionally, the emergence of SARS-CoV-2 variants of concern with their potential to escape therapeutic monoclonal antibodies emphasizes the need to develop second-generation oral antivirals targeting highly conserved viral proteins that can be rapidly deployed to outpatients. Here, we demonstrate the in vitro antiviral activity and in vivo therapeutic efficacy of GS-621763, an orally bioavailable prodrug of GS-441524, the parental nucleoside of remdesivir, which targets the highly conserved RNA-dependent RNA polymerase. GS-621763 exhibited significant antiviral activity in lung cell lines and two different human primary lung cell culture systems. The dose-proportional pharmacokinetic profile observed after oral administration of GS-621763 translated to dose-dependent antiviral activity in mice infected with SARS-CoV-2. Therapeutic GS-621763 significantly reduced viral load, lung pathology, and improved pulmonary function in COVID-19 mouse model. A direct comparison of GS-621763 with molnupiravir, an oral nucleoside analog antiviral currently in human clinical trial, proved both drugs to be similarly efficacious. These data demonstrate that therapy with oral prodrugs of remdesivir can significantly improve outcomes in SARS-CoV-2 infected mice. Thus, GS-621763 supports the exploration of GS-441524 oral prodrugs for the treatment of COVID-19 in humans.

4.
PubMed; 2020.
Preprint in English | PubMed | ID: ppcovidwho-333566

ABSTRACT

The COVID-19 pandemic has revealed that infection with SARS-CoV-2 can result in a wide range of clinical outcomes in humans, from asymptomatic or mild disease to severe disease that can require mechanical ventilation. An incomplete understanding of immune correlates of protection represents a major barrier to the design of vaccines and therapeutic approaches to prevent infection or limit disease. This deficit is largely due to the lack of prospectively collected, pre-infection samples from indiviuals that go on to become infected with SARS-CoV-2. Here, we utilized data from a screen of genetically diverse mice from the Collaborative Cross (CC) infected with SARS-CoV to determine whether circulating baseline T cell signatures are associated with a lack of viral control and severe disease upon infection. SARS-CoV infection of CC mice results in a variety of viral load trajectories and disease outcomes. Further, early control of virus in the lung correlates with an increased abundance of activated CD4 and CD8 T cells and regulatory T cells prior to infections across strains. A basal propensity of T cells to express IFNg and IL17 over TNFa also correlated with early viral control. Overall, a dysregulated, pro-inflammatory signature of circulating T cells at baseline was associated with severe disease upon infection. While future studies of human samples prior to infection with SARS-CoV-2 are required, our studies in mice with SARS-CoV serve as proof of concept that circulating T cell signatures at baseline can predict clinical and virologic outcomes upon SARS-CoV infection. Identification of basal immune predictors in humans could allow for identification of individuals at highest risk of severe clinical and virologic outcomes upon infection, who may thus most benefit from available clinical interventions to restrict infection and disease. SUMMARY: We used a screen of genetically diverse mice from the Collaborative Cross infected with mouse-adapted SARS-CoV in combination with comprehensive pre-infection immunophenotyping to identify baseline circulating immune correlates of severe virologic and clinical outcomes upon SARS-CoV infection.

5.
PubMed; 2020.
Preprint in English | PubMed | ID: ppcovidwho-331914

ABSTRACT

A safe, effective, and scalable vaccine is urgently needed to halt the ongoing SARS-CoV-2 pandemic. Here, we describe the structure-based design of self-assembling protein nanoparticle immunogens that elicit potent and protective antibody responses against SARS-CoV-2 in mice. The nanoparticle vaccines display 60 copies of the SARS-CoV-2 spike (S) glycoprotein receptor-binding domain (RBD) in a highly immunogenic array and induce neutralizing antibody titers roughly ten-fold higher than the prefusion-stabilized S ectodomain trimer despite a more than five-fold lower dose. Antibodies elicited by the nanoparticle immunogens target multiple distinct epitopes on the RBD, suggesting that they may not be easily susceptible to escape mutations, and exhibit a significantly lower binding:neutralizing ratio than convalescent human sera, which may minimize the risk of vaccine-associated enhanced respiratory disease. The high yield and stability of the protein components and assembled nanoparticles, especially compared to the SARS-CoV-2 prefusion-stabilized S trimer, suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms for inducing potent neutralizing antibody responses and have launched cGMP manufacturing efforts to advance the lead RBD nanoparticle vaccine into the clinic.

6.
Physioscience ; : 11, 2022.
Article in German | Web of Science | ID: covidwho-1721674

ABSTRACT

Background Knee osteoarthritis is one of the main causes of disability and mobility impairment in the elderly population. This is associated with suffering and high medical costs. Non-surgical therapy such as exercise therapy, physical activity interventions and self-management support can reduce pain and improve function and health-related quality of life. Home exercise programs are considered an important component of therapy, but adherence is often insufficient. Digital health applications are a promising option, especially under the conditions of the current COVID-19 pandemic to reduce this barrier. Objective To investigate the feasibility of implementing a mHealth home exercise program for patients with knee osteoarthritis in terms of usability, user experience, user behaviour and outcome. Method Patients with knee osteoarthritis carried out the mHealth home exercise program (mhexos) for 4 weeks. The program was implemented via tablet computer with a total of 39 exercise videos on strengthening, balance and coordination, which could be configured in 3 difficulty levels. Data on pain intensity and self-perceived exertion were recorded via the app. Guided interviews were conducted and questionnaires were used to assess usability and user experience as well as health-related outcomes at 2 measurement points. Results 10 patients and 7 therapists were included. The mHealth home exercise programme could be implemented in the practice and the everyday life of the subjects. The app was predominantly rated as user-friendly and motivating, adherence to therapy was high with an exercise frequency of 2.7 times per week (SD 0.6). The health-related outcomes showed small, statistically non-significant and clinically not relevant changes following the intervention. Conclusion The mhexos seems to be suitable to support home exercise programs for knee osteoarthritis under given conditions. Controlled studies are needed to assess its effectiveness.

7.
MEDLINE;
Preprint in English | MEDLINE | ID: ppcovidwho-326687

ABSTRACT

The emergence of current SARS-CoV-2 variants of concern (VOCs) and potential future spillovers of SARS-like coronaviruses into humans pose a major threat to human health and the global economy 1-7 . Development of broadly effective coronavirus vaccines that can mitigate these threats is needed 8, 9 . Notably, several recent studies have revealed that vaccination of recovered COVID-19 donors results in enhanced nAb responses compared to SARS-CoV-2 infection or vaccination alone 10-13 . Here, we utilized a targeted donor selection strategy to isolate a large panel of broadly neutralizing antibodies (bnAbs) to sarbecoviruses from two such donors. Many of the bnAbs are remarkably effective in neutralization against sarbecoviruses that use ACE2 for viral entry and a substantial fraction also show notable binding to non-ACE2-using sarbecoviruses. The bnAbs are equally effective against most SARS-CoV-2 VOCs and many neutralize the Omicron variant. Neutralization breadth is achieved by bnAb binding to epitopes on a relatively conserved face of the receptor binding domain (RBD) as opposed to strain-specific nAbs to the receptor binding site that are commonly elicited in SARS-CoV-2 infection and vaccination 14-18 . Consistent with targeting of conserved sites, select RBD bnAbs exhibited in vivo protective efficacy against diverse SARS-like coronaviruses in a prophylaxis challenge model. The generation of a large panel of potent bnAbs provides new opportunities and choices for next-generation antibody prophylactic and therapeutic applications and, importantly, provides a molecular basis for effective design of pan-sarbecovirus vaccines.

9.
Journal of the American Academy of Child and Adolescent Psychiatry ; 60(10):S289, 2021.
Article in English | EMBASE | ID: covidwho-1466499

ABSTRACT

Objectives: As delivery of psychological interventions by nonspecialists becomes more commonplace, assurance that training and supervision methods achieve minimum competency standards is needed. The United Nations Children’s Fund and World Health Organization (UNICEF-WHO) Ensuring Quality in Psychological Support (EQUIP) platform is a digital tool to provide guidance on conducting competency-based trainings of nonspecialists. The platform includes competency assessment tools for adults (the ENhancing Assessment of Common Therapeutic Factors [ENACT] tool) and for children (Working with children—Assessment of Competencies Tool [WeACT]), as well as a suite of treatment-specific competency tools for adult- and child-focused psychological interventions. Methods: Role-play based (RPB) competency assessment tools were evaluated in a range of global settings for feasibility and acceptability. Study sites included Ethiopia, Kenya, Lebanon, Nepal, the occupied Palestinian territory, Peru, Uganda, and Zambia. In addition, a US pilot of the tool was conducted in New York City (NYC). Acceptability and feasibility were evaluated through both qualitative assessments and evaluation of interrater reliability (IRR) and responsivity to change. Results: IRR ranged from 0.54 to 0.80 across sites and tools. The use of microcompetency video demonstrations of helpful vs potential harmful/unhelpful techniques helped increase IRR. Most individual competencies showed responsivity to change when evaluated pre- vs posttraining. For child competencies, youth drama clubs were feasibly trained to be actors in the standardized role-plays. Competencies were also modified for remote delivery of psychological interventions, which is of particular importance to deliver services during the COVID-19 pandemic. Conclusions: RPB assessments of competencies can be implemented in diverse settings ranging from refugee camps in low-income countries to urban centers of high-income countries (HICs). Rater training and standardized actors require a significant time investment, which can then yield high rates of IRR for observational assessments. With the transition to more remote care, RPB structured competency assessments are increasingly feasible even in low-resource settings. Reciprocal learning with the NYC site demonstrated that the tool can also be beneficial in an HIC. R, OTH

10.
Intervention ; 19(1):107-117, 2021.
Article in English | Scopus | ID: covidwho-1183964

ABSTRACT

Problem Management Plus (PM+) is used to address mental health needs in humanitarian emergencies, including in response to COVID-19. Because PM+ is designed for non-specialist facilitators, one challenge is ensuring that trainees have the necessary competencies to effectively deliver the intervention and not cause unintended harm. Traditional approaches to evaluating knowledge of an intervention, such as written tests, may not capture the ability to demonstrate PM+ skills. As part of the World Health Organization Ensuring Quality in Psychological Support (EQUIP) initiative, we developed a structured competency rating tool to be used with observed standardised role plays. The role plays were designed to elicit demonstration of the key mechanisms of action for PM+. These role plays can be objectively rated by trainers, supervisors or other evaluators to determine facilitators' competency levels in PM+. These competency assessments can highlight what skills require additional attention during training and supervision, thus supporting facilitators to fill gaps in competencies. The integration of role plays in training and supervision also allows organisations to establish quality control metrics for competency standards to deliver PM+. We describe lessons learned from piloting the PM+ competency role plays with the Center for Victims of Torture programme with Eritrean refugees in Ethiopia. © 2021 Lippincott Williams and Wilkins. All rights reserved.

11.
Journal of Immunology ; 204(1), 2020.
Article in English | EMBASE | ID: covidwho-881910

ABSTRACT

Immune homeostasis is the state where the immune system maintains stability in the absence of insult. Much of the analysis of immune homeostasis has focused on systemic immunity, but it is also likely to be important in an organ specific manner. There is evidence that homeostatic immunity can affect subsequent responses to infection or vaccination. Since the lungs are a major site of infection, we used the Collaborative Cross (CC) mouse genetic reference population to study the genetic regulation of the breadth of baseline immune cell populations in the lung and identify loci regulating these cells at the steady state. We found that all immune cell populations measured showed strong genetic (i.e. strain-specific) variation in cell type abundances. We identified 12 quantitative trait loci (QTL) associated with variation in 12 immune cell populations or the relationships between cell populations. Given the role of various immune cells in the lungs during respiratory virus pathogenesis, we asked whether any of the mapped QTL correlated with influenza A virus (IAV) or Severe acute respiratory syndrome associated coronavirus (SARS-CoV) disease following infection in the same strains of mice. Notably, a locus we mapped for baseline abundance of CD8+ T cells in the lungs was associated with peak weight loss following IAV infection. Additionally, a locus mapped for variation in Ly6C+ monocyte/macrophage abundance was associated with SARS-CoV titer at days 2 and 4 post-infection. These data suggest that abundance of lung leukocyte populations prior to infection could serve as predictors of immune responses to respiratory viruses.

SELECTION OF CITATIONS
SEARCH DETAIL