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Background Older people living in care homes are at high risk of poor health outcomes and mortality if they contract coronavirus disease 2019. Protective measures include social distancing and isolation, although implementation is challenging. Objectives To explore the real-life experiences of social distancing and isolation in care homes for older people, and to develop a toolkit of guidance and resources. Design A mixed-methods, phased design. Setting Six care homes in England caring for older adults. Participants Care home staff (n = 31), residents (n = 17), family members (n = 17), senior health and care leaders (n = 13). Methods A rapid review to assess the social distancing and isolation measures used by care homes to control the transmission of coronavirus disease 2019 and other infectious diseases (phase 1), in-depth case studies of six care homes, involving remote individual interviews with staff, residents and families, collection of policies, protocols and routinely collected care home data, remote focus groups with senior health and care leaders (phase 2) and stakeholder workshops to co-design the toolkit (phase 3). Interview and focus group data and care home documents were analysed using thematic analysis and care home data using descriptive statistics. Results The rapid review of 103 records demonstrated limited empirical evidence and the limited nature of policy documentation around social distancing and isolation measures in care homes. The case studies found that social distancing and isolation measures presented moral dilemmas for staff and often were difficult, and sometimes impossible to implement. Social distancing and isolation measures made care homes feel like an institution and denied residents, staff and families of physical touch and other forms of non-verbal communication. This was particularly important for residents with cognitive impairment. Care homes developed new visiting modalities to work around social distancing measures. Residents and families valued the work of care homes to keep residents safe and support remote communication. Social distancing, isolation and related restrictions negatively impacted on residents’ physical, psychological, social and cognitive well-being. There were feelings of powerlessness for families whose loved ones had moved into the care home during the pandemic. It was challenging for care homes to capture frequent updates in policy and guidance. Senior health and care leaders shared that the care home sector felt isolated from the National Health Service, communication from government was described as chaotic, and trauma was inflicted on care home staff, residents, families and friends. These multiple data sources have informed the co-design of a toolkit to care for residents, families, friends and care home staff. Limitations The review included papers published in English language only. The six care homes had a Care Quality Commission rating of either ‘good’ or ‘outstanding’. There was a lack of ethnic diversity in resident and family participants. Conclusions Care homes implemented innovative approaches to social distancing and isolation with varying degrees of success. A legacy of learning can help rebuild trust at multiple levels and address trauma-informed care for residents, families, friends and staff. Future work can include evaluation of the toolkit, research to develop a trauma-informed approach to caring for the care home sector and co-designing and evaluating an intervention to enable residents with different needs to transition to living well in a care home. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR132541) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 45. See the NIHR Funding and Awards website for further award information. Plain language summary Older people living in care homes are at risk of poor health and death if they get coronavirus disease 2019 (COVID-19). To protect older people from COVID-19, care homes use different measures, including social distancing and isolation. These measures can be challenging. Our research aimed to explore the challenges and solutions to using social distancing and isolation in care homes. We reviewed existing evidence to examine how care homes have used social distancing and isolation measures to control the spread of COVID-19 and other contagious diseases. We investigated how social distancing and isolation measures have been used in six care homes in England. We spoke with residents, families and staff. We collected care home documents and other data. We held group discussions with senior health and care leaders. The review showed limited research and the limited nature of policy documentation on social distancing and isolation measures. Interviews revealed that social distancing and isolation measures were difficult, and sometimes impossible, for staff to implement. These measures made care homes feel less homely and inhibited touch, for example hugs. Residents and families valued the work of care homes to keep residents safe and the use of technology for keeping connected. Social distancing, isolation and related restrictions negatively affected residents’ physical, psychological, social and cognitive well-being. There were feelings of powerlessness for families whose loved ones had moved into the care home during the pandemic. It was challenging for care homes to capture frequent updates in policy and guidance. Senior health and care leaders shared that the care home sector felt isolated from the National Health Service, communication from government to the care home sector was described as chaotic and trauma was inflicted on care home staff, residents, families and friends. These findings have been used to design guidance to help care homes implement social distancing and isolation measures both now and for any future outbreaks. Scientific summary Background Older people living in care homes (CHs) (i.e. homes that provide residential and/or nursing care) often have complex health and care needs and are at high risk of poor health outcomes and mortality, especially if they contract coronavirus disease 2019 (COVID-19). To protect older people from COVID-19, CHs use interventions such as social distancing and isolation, but these measures have been reported as challenging. Research is needed to explore and understand the challenges experienced by CHs endeavouring to implement these interventions while mitigating any negative consequences. Objectives The overall aim of the study was to explore and understand the real-life experiences of social distancing and isolation measures for older people living in CHs in England from the perspective of multiple stakeholders, and to develop a toolkit of evidence-informed guidance and resources for CHs now and for future outbreaks. The study objectives were as follows: (1) to investigate the mechanisms and measures used by CHs currently and previously to socially distance and isolate older people to prevent and control the spread of COVID-19 and other infectious and contagious diseases (2) to examine the experiences of residents and families/friends of social distancing and isolation measures during the COVID-19 pandemic, including how these measures impacted upon their well-being and how they adapted to change (3) to explore how registered nurses and care staff adapted to and managed the delivery of personal, social and psychological care for residents with different needs while maintaining social distancing and isolation measures (4) to identify how CH managers, owners and external stakeholders developed, managed and adapted policies, procedures and protocols to implement social distancing and isolation measures including workforce organisation, training and support, use of communal spaces, visiting, and working with external health and social care professionals (5) to use the findings to develop a toolkit of evidence-informed guidance and resources, including a mosaic film, detailing which interventions and strategies for social distancing and isolation work well and which do not work in specific situations and contexts to support decision-making about health and care delivery in CHs and to facilitate resilience-building for future planning. Methods A mixed-methods, phased design was undertaken to identify the challenges, consequences and solutions to implementing social distancing and isolation measures in CHs for older adults to prevent and control the spread of COVID-19. The study was conducted in three phases: (1) a rapid evidence review of measures used to prevent or control the transmission of COVID-19 and other infectious diseases in CHs for older people, following the guidance for conducting rapid reviews1 (2) in-depth case studies of six purposively sampled CHs in England involving individual interviews with care staff, managers, residents and family/friends, the collection of social distancing and isolation policies/protocols and routinely collected CH data, and focus groups with purposively sampled CH owners and external stakeholders. Reporting guidance for qualitative research was used2 (3) development of a toolkit of evidence-informed guidance and resources, and a mosaic film for CHs. The findings from earlier phases were used in two co-design workshops with external stakeholders to develop the toolkit. Findings from the 103 papers included in the rapid review were synthesised using tables and a narrative summary organised around the review questions. Interview audio-recordings were transcribed verbatim and data analysed using thematic analysis. Descriptive summary statistics described the quantitative data collected. For the CH documents, information was collated around the key themes of social distancing, isolation, cohorting, zoning and other restrictions. Concurrent data collection and analysis informed decision-making about the need for further data and from which source. Patient and public involvement (PPI) was an integral part of this study, informing its design, method, analysis and dissemination. PPI group members also participated in online workshops to contribute to the co-design of the toolkit. Results The rapid review highlighted the following: There is a lack of empirical evidence around how measures to prevent or control COVID-19 and other infectious diseases are implemented in CHs. Most papers were grey literature or policy documents, which were mainly descriptive, or opinion based. Furthermore, these interventions were generally mentioned as part of a wider discussion of COVID-19 strategies and were not the primary focus of the papers. Key interventions for preventing and controlling the transmission of COVID-19 and other infectious diseases in CHs for older people include social distancing; isolation of residents and staff; restrictions for residents, family members and staff; zoning and cohorting; and surveillance. Evaluative research on the use of these interventions in CHs is needed urgently. The six case study sites were geographically spread and all had a Care Quality Commission rating of good (n = 4) or outstanding (n = 2). All were part of organisations (ranging in size from 7 to 114 CHs per organisation, and between 767 and 5875 beds per organisation). Four of the CHs were part of privately run organisations, and two were part of voluntary/not-for-profit organisations. One CH had a ‘dual’ registration, three had a ‘nursing’ registration and two were registered as ‘without nursing’. Most provided some specialist care such as for dementia, learning disabilities, physical and mental health problems. The number of beds offered ranged between 37 and 73. One CH comprised a household of 12 residents within a village complex. Care homes varied on the number of positive COVID-19 cases, for example one reported only one case between March 2020 and February 2021, while another reported 27 cases within the month November 2020 alone – this home had opened a specially allocated ‘COVID-ward’. In one CH no residents had died within 28 days of a positive COVID-19 test, while 10 residents had died from another home. Policies and protocols about social distancing and isolation measures were collected from each CH and compared. Key findings were as follows: There was significant variation between CHs in the content, length and level of detail presented in policy and guidance documents. Capturing the frequent updates in guidance was challenging with documents sometimes being repetitive and unclear. Many documents had further, embedded documents or links to government guidance that provided a great deal of information, which might be unrealistic for CH staff to read. Shorter documents were less comprehensive and may not provide the necessary detail to guide CH staff. None of the documents included guidance on staff training and development. Research at the case study sites included individual interviews with 31 CH staff. Key findings were as follows: The impact that the COVID-19 pandemic had upon CH staff must not be underestimated. Staff reported trauma and emotional distress. For many staff, the difficulties experienced during the pandemic were compounded by the government’s response to CHs. Some staff felt they had been abandoned by the government, while others criticised the ‘blanket approach’ to government guidance and the rapidly changing rules for CHs. Care home managers valued the support of their senior leadership to help them interpret and implement government guidance. Staff talked of the difficulties of ‘policing’ social distancing measures while simultaneously trying to maintain a sense of ‘normality’ for their residents. Although staff and residents were supposed to maintain a social distance from each other, this was often impossible to uphold when providing personal care. Care homes were perceived as a resident’s home rather than an institution, which made some staff question whether social distancing was appropriate. Many staff felt that social distancing measures denied residents (and themselves) of the important need for touch, as hugs were felt to have a vital role in CH life. Understanding fully the impact on residents living with dementia was recognised as a challenge and not always possible to achieve. The design and layout of CHs meant that there was not always the physical space for social distancing to be implemented. Staff felt that new admissions to CHs had the most difficult experience with isolation regulations. For some managers, isolation measures went against the ethos of the CH environment and ruined the family feel of the CH. The requirement for residents to isolate when returning from hospital could lead to a reluctance in residents to attend hospital appointments and a disinclination of staff to refer residents for hospital care. Several different resident restrictions were implemented in CHs, but restrictions around residents leaving the home, changes to food preparation/delivery and visitor restrictions were perceived to have the greatest negative impact. On occasions, staff became a target of anger and frustration from residents and their families, who could not comprehend that they were being prevented from seeing each other. Good support from CH management was considered by staff to make the process of implementing these measures easier. Individual interviews were conducted with 17 residents and 17 family members. Key findings were as follows: The experiences of residents and families were varied, and their impact was influenced by the existing pattern of relationships residents and families maintained within and beyond the CH. Residents and families valued the work of the CHs in keeping residents safe. They accepted the need for restrictions. Residents and families appreciated the support they received in communicating with one another virtually and the importance of this communication for residents’ health and well-being. Measures relating to isolation were particularly difficult for residents, particularly for those unable to communicate with the outside world through technology. Measures to make isolation less difficult for residents included ensuring that they were entertained purposefully with regular socially distanced visits from staff and various resources to occupy their time. Creative approaches to activities for residents not isolating were also evidenced, for example indoor gardening, yoga and quizzes. Social distancing made aspects of CH life and social visiting difficult and sometimes unsatisfactory; residents and families missed physical touch and other non-verbal forms of communication. This was particularly important for residents with cognitive impairment. Residents and families were involved with staff in complex judgements of risk, choice and control, which were complicated by two factors. First, families (and some residents) were aware that those in CHs were in the twilight of their lives and that time was ebbing away. Second, many families and residents were also learning how to manage their relationships in the new living context of a CH. Two focus groups were conducted with a purposive sample of 13 external senior health and care leaders. Key findings were as follows: Isolation of the sector: the sector felt cut off from the National Health Service (NHS) and pre-pandemic sources of service and support. Government guidance for CHs and communication processes: ‘chaos’ described the approach to cascading information to CHs, especially in the first wave of the pandemic. Visiting: regulations evolved throughout the different waves of the pandemic and led to variations in interpreting and implementing visiting guidance. Trauma: as the pandemic wore on and the different waves and variants emerged, there was a need to take account of the broader health and well-being of residents, families, visitors and the workforce. Trauma impacted at several different levels – for staff, residents and family members. Implications for practice and policy For practice Implications of the study findings for practice are captured in our toolkit for supporting CHs with social distancing and isolation measures. These are framed around six areas: caring for residents when they are social distancing; caring for residents when they are isolating; supporting residents, families and friends to communicate when visiting is not permitted; supporting visits from families and friends when visiting is allowed but with restrictions; caring for care staff; and caring for managers. For policy The study findings can inform discussions involving CH providers, managers and external stakeholders to enhance understanding of social distancing and isolation measures for residents – consequences, challenges, solutions and learning. Our findings also have implications about how guidelines are developed and disseminated. They reinforce the need for CHs and social care to be considered as an integral part of integrated care systems, to ensure that actions taken during national emergencies fully account for the impact on all parts of health and social care. Our findings can inform discussions about developing digital technologies to help residents with different needs stay connected with families and friends, and for CHs to communicate effectively with residents’ families and friends. Our findings can contribute to the content of the digital hub for the social care workforce. Recommendations for further research This study has identified that research is needed in several areas including the following: Evaluations of the toolkit. Evaluation of social distancing and isolation measures used in CHs to prepare for future pandemics. Research to develop and evaluate remote social interaction for residents living with dementia and their families. Research to understand what a trauma-informed approach looks like for the CH sector – to care for residents, families, friends and staff in CHs caring for older people. Research to co-design and evaluate an intervention to enable residents with different needs to transition to living well in a CH. The study of an intervention that cares for families and friends. Conclusions The CH sector was ill-prepared and under-resourced for the COVID-19 pandemic. During the pandemic and for any further surges, it is paramount that CH services are safe, effective, caring, responsive to individual needs and well-led. The loss of older people living in CHs due to COVID-19 has been substantial; it is essential to learn from this devastation, to understand the consequences, challenges, solutions and to evaluate these solutions. Evidence to support learning and recovery of the CH sector from the pandemic and to inform policy-making is paramount. Care homes need evidence-informed guidance that sets out what and how social distancing and isolation measures should be operationalised, while meeting residents’ individual needs. Our toolkit is designed to capture such innovative approaches. Our study makes an important contribution to this learning and recovery, as one of the first to study the challenges and solutions to implementing social distancing and isolation measures for older people living in CHs in England. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR132541) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 45. See the NIHR Funding and Awards website for further award information.

IntroductionThe Implementation Research Logic Model (IRLM) aids users in combining, organizing, and specifying the relationships between important constructs in implementation research. The goal of the IRLM is to improve the rigor, reproducibility, and transparency of implementation research projects. The article describing the IRLM was published September 25, 2020 (Implement Sci, Vol 15); it has since been highly cited and included as a required element in multiple funding opportunity announcements from federal agencies. The proliferation of IRLM use across dissemination and implementation research projects and practice provides an excellent opportunity to examine applications across a variety of different contexts. This protocol will result in a description of the impact of the IRLM on the field of dissemination and implementation science and guidance on refinements to the IRLM to increase its utility and impact through (1) a citation analysis, (2) a scoping review, and (3) user surveys and interviews.Methods and analysisThis protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping review reporting guidelines (PRISMA-ScR). We plan to conduct a citation search and analysis of the Smith et al. 2020 article and a scoping review. The review search will be conducted in Medline, Embase, CINAHL Complete, Cochrane Library, APA PsycINFO4, ProQuest Dissertations & Theses Global, Scopus and Web of Science Core Collection., and grey literature will be searched to identify studies that use alternative logic models for implementation research. A survey will be developed from the findings of the scoping review and administered to individuals who used the IRLM. Semi-structured interviews will then be conducted with a sample of survey respondents to provide an opportunity for sequential mixed-methods analysis to achieve a deeper understanding of needed IRLM refinements and recommendations.Ethics and disseminationEthics approval for the scoping review and citation analysis is not applicable as only data from published literature will be used and no original data will be collected. For the survey, IRB will be completed once items are developed from the results of the scoping review and citation analysis. Results will be disseminated through peer-reviewed publications, conference presentations, and via online tools. Registration detailsThis protocol was registered with OSF, https://osf.io/y94bj (1).

Background & Objectives Trial Emulation methods can be applied to Population-Scale Linked Electronic Health Records (EHR) to generalise the results of Randomised Controlled Trials (RCTs) to a broader patient population. However, the Data Generating Mechanisms (DGMs) associated with EHR data mean that there is a need to adjust for informative observations, i.e. worse prognosis patients may have more observations. Approach Using the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) as a case study: a RCT of a calcium-channel blocker-based regimen versus a β-blocker-based regimen, an emulated trial was created from population-scale, individual-level, linked anonymized EHR data curated as part of the Wales Multimorbidity e-cohort (WMC) for individuals who would have been eligible for ASCOT-BPLA but who also had Multiple Long-Term Conditions (MLTCs). Outcomes were systolic and diastolic blood pressure estimated/predicted at treatment initiation, 6 weeks, 3 months, and 6 monthly until 4 years. Methods & Results Predictions were made using a fully probabilistic Bayesian joint model which allowed for dropout due to death and which either did or did not also adjust for the frequency of blood pressure observations available. In previous simulation studies such a joint modelling approach has been shown to out-perform other adjustment methods in terms of bias and coverage. Conclusions & Implications Whilst EHR data offer an attractive platform in which to evaluate interventions in people living with MLTCs, the inherent DGMs associated with them need to be taken into account, and the use of a joint modelling approach is an attractive way to achieve this.

Background and Objectives Polypharmacy is increasingly common in people living with multiple long-term conditions (MLTC), but clinical evidence often does not consider medicine interactions beyond two or three treatments at a time. The aim of this research is to develop statistical models to better understand interactions between treatments leading to adverse events for people living with MLTC. Approach We will develop models of risk of adverse events in people with MLTC and polypharmacy using data in the Secure Anonymised Information Linkage (SAIL) Databank - a trusted research environment with linked electronic health record data at the individual-level for the population of Wales, UK. Taking a flexible Bayesian joint modelling approach, where the posterior risk is the product of several sub-models, will enable the characterisation of this complex system in a way that is interpretable for healthcare decision-makers, leading to improved understanding of risk factors for adverse events. Results The Welsh Multimorbidity e-Cohort (WMC) includes 2.9 million people alive and living in Wales on 1st Jan 2000 with follow-up for 20 years. Individuals in the cohort have 932,552,061 medication items prescribed and 277,279 coded adverse events recorded in primary care data. Modelling approaches will focus on feasibility of fitting models to population-level datasets, and the interpretability of the model results for healthcare decision-making. Conclusions and Implications Results have the potential to inform healthcare policy and practice for the management of people living with MLTC and polypharmacy, thus improving patient outcomes and making the best use of limited healthcare resources.

Background and Objectives Healthcare decision-making has previously focused on developing recommendations for single conditions. This research aimed to develop a modeling framework to estimate the effects of multi-indication treatment in people living with multiple long-term conditions. Approach Using a case study in type 2 diabetes mellitus [T2DM], chronic kidney disease [CKD], and heart failure [HF], age-adjusted multistate models were used to estimate the effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors as a multi-indication treatment. Baseline hazards were estimated using population-scale, individual-level, linked anonymized electronic health record (EHR) data for 613,195 individuals aged 55 to 85 years in Wales over a 20-year period. Hazard ratios for treatment effects compared to standard of care were obtained from randomized controlled trials for combinations of multiple-long term conditions and incorporated in a patient-level simulation. Results SGLT2 inhibitors increased the estimated mean life expectancy from 0.02 (95% Confidence Interval (CI): -0.02, 0.05) to 1.44 (95% CI: 1.12, 1.74) years in people living with coexisting T2DM, CKD, and HF. The estimated gain in life expectancy was less than 0.5 years for individuals with T2DM, CKD, and HF in different temporally ordered sequences. The estimated mean time to develop HF increased by 3.1 (95% CI: 3.00, 3.24) and 1.34 (95% CI: 1.12, 1.56) years in individuals with CKD, and in those with CKD followed by T2DM. Conclusions and Implications There is an ever increasing need to appraise interventions in people living with multiple long-term conditions to identify optimal treatment strategies and reduce polypharmacy. Multistate models applied to linked EHRs allow for a more rigorous assessment of treatment effects to inform healthcare policy.

Enterococci are robust Gram-positive bacteria that pose a significant threat in healthcare settings due to antibiotic resistance, with vancomycin-resistant enterococci (VRE) most prominent. To tackle this issue, bacteriophages (bacterial viruses) can be exploited as they specifically and efficiently target bacteria. Here, we successfully isolated and characterised a set of novel phages: SHEF10, SHEF11, SHEF13, SHEF14, and SHEF16 which target E. faecalis (SHEF10,11,13), or E. faecium (SHEF13, SHEF14 & SHEF16) strains including a range of clinical and VRE isolates. Genomic analysis shows that all phages are strictly lytic and diverse in terms of genome size and content, quickly and effectively lysing strains at different multiplicity of infections. Detailed analysis of the broad host-range SHEF13 phage revealed the crucial role of the enterococcal polysaccharide antigen (EPA) variable region in its infection of E. faecalis V583. In parallel, the discovery of a carbohydrate-targeting domain (CBM22) found conserved within the three phage genomes indicates a role in cell surface interactions that may be important in phage-bacterial interactons. These findings advance our comprehension of phage-host interactions and pave the way for targeted therapeutic strategies against antibiotic-resistant enterococcal infections.

Objective: To identify highest-risk subgroups for COVID-19 and Long COVID(LC), particularly in contexts of influenza and cardiovascular disease(CVD). Methods: Using national, linked electronic health records for England (NHS England Secure Data Environment via CVD-COVID-UK/COVID-IMPACT Consortium), we studied individuals (of all ages) with COVID-19 and LC (2020-2023). We compared all-cause hospitalization and mortality by prior CVD, high CV risk, vaccination status (COVID-19/influenza), and CVD drugs, investigating impact of vaccination and CVD prevention using population preventable fractions. Results: Hospitalization and mortality were 15.3% and 2.0% among 17,373,850 individuals with COVID-19 (LC rate 1.3%), and 16.8% and 1.4% among 301,115 with LC. Adjusted risk of mortality and hospitalization were reduced with COVID-19 vaccination ≥ 2 doses(COVID-19:HR 0.36 and 0.69; LC:0.44 and 0.90). With influenza vaccination, mortality was reduced, but not hospitalization (COVID-19:0.86 and 1.01, and LC:0.72 and 1.05). Mortality and hospitalization were reduced by CVD prevention in those with CVD, e.g., anticoagulants- COVID:19:0.69 and 0.92; LC:0.59 and 0.88; lipid lowering- COVID-19:0.69 and 0.86; LC:0.68 and 0.90. COVID-19 vaccination averted 245044 of 321383 and 7586 of 8738 preventable deaths after COVID-19 and LC, respectively. Interpretation: Prior CVD and high CV risk are associated with increased hospitalization and mortality in COVID-19 and LC. Targeted COVID-19 vaccination and CVD prevention are priority interventions. Funding: NIHR. HDR UK.

BackgroundCommon, operational definitions are crucial to assess interventions and outcomes related to pediatric mechanical ventilation. These definitions can reduce unnecessary variability among research and quality improvement efforts, to ensure findings are generalizable, and can be pooled to establish best practices.Research questionCan we establish operational definitions for key elements related to pediatric ventilator liberation using a combination of detailed literature review and consensus-based approaches?Study design and methodsA panel of 26 international experts in pediatric ventilator liberation, two methodologists, and two librarians conducted systematic reviews on eight topic areas related to pediatric ventilator liberation. Through a series of virtual meetings, we established draft definitions that were voted upon using an anonymous web-based process. Definitions were revised by incorporating extracted data gathered during the systematic review and discussed in another consensus meeting. A second round of voting was conducted to confirm the final definitions.ResultsIn eight topic areas identified by the experts, 16 preliminary definitions were established. Based on initial discussion and the first round of voting, modifications were suggested for 11 of the 16 definitions. There was significant variability in how these items were defined in the literature reviewed. The final round of voting achieved ≥ 80% agreement for all 16 definitions in the following areas: what constitutes respiratory support (invasive mechanical ventilation and noninvasive respiratory support), liberation and failed attempts to liberate from invasive mechanical ventilation, liberation from respiratory support, duration of noninvasive respiratory support, total duration of invasive mechanical ventilation, spontaneous breathing trials, extubation readiness testing, 28 ventilator-free days, and planned vs rescue use of post-extubation noninvasive respiratory support.InterpretationWe propose that these consensus-based definitions for elements of pediatric ventilator liberation, informed by evidence, be used for future quality improvement initiatives and research studies to improve generalizability and facilitate comparison.

INTRODUCTION: Deep brain stimulation (DBS) is an effective treatment for Parkinsons disease (PD), but its efficacy is tied to DBS programming, which is often time consuming and burdensome for patients, caregivers, and clinicians. Our aim is to test whether the Mobile Application for PD DBS (MAP DBS), a clinical decision support system, can improve programming. METHODS: We conducted an open-label, 1:1 randomized, controlled, multicenter clinical trial comparing six months of SOC standard of care (SOC) to six months of MAP DBS-aided programming. We enrolled patients between 30 and 80 years old who received DBS to treat idiopathic PD at six expert centers across the United States. The primary outcome was time spent DBS programming and secondary outcomes measured changes in motor symptoms, caregiver strain and medication requirements. RESULTS: We found a significant reduction in initial visit time (SOC: 43.8 ± 28.9 min n = 37, MAP DBS: 27.4 ± 13.0 min n = 35, p = 0.001). We did not find a significant difference in total programming time between the groups over the 6-month study duration. MAP DBS-aided patients experienced a significantly larger reduction in UPDRS III on-medication scores (-7.0 ± 7.9) compared to SOC (-2.7 ± 6.9, p = 0.01) at six months. CONCLUSION: MAP DBS was well tolerated and improves key aspects of DBS programming time and clinical efficacy.

The Anopheles stephensi mosquito is a major vector of malaria in south Asia, the Middle East, and southern China, where it is endemic and is known to transmit both Plasmodium [...]

To improve the wear resistance of CoCrFeNi high-entropy alloys (HEAs) for a wider range of industrial applications, the alloying strategy was applied to CoCrFeNi HEA by doping Mo element in various ratios, and CoCrFeNiMox (x = 0, 0.2, 0.5, and 1.0) HEA deposits were fabricated by cold spray. The microstructure evolution, mechanical properties, and tribological properties of cold-sprayed CoCrFeNiMox HEA deposits were systematically investigated. The results showed that Mo0, Mo0.2, and Mo0.5 deposits have a face-centered-cubic (FCC) single structure, while Mo1.0 deposit was composed of FCC matrix and hard brittle phases. The doping of Mo element into CoCrFeNi HEA deposits significantly increased the hardness due to the enhanced solid solution strengthening and precipitation strengthening. As a result, the anti-wear properties of Mo-doped CoCrFeNi HEA deposits were gradually improved with the increase in Mo ratios. To be specific, the Mo1.0 deposit exhibited the lowest specific wear rate of 5.1 × 10−5 mm3/N·m, which was reduced by 94.9% in comparison to the Mo0 deposit. Overall, the current study proposes a new strategy to manipulate the mechanical properties of cold-sprayed HEA deposits by alloying.