Models and approaches for building knowledge translation capacity and capability in health services: a scoping review.

BACKGROUND: Building healthcare service and health professionals' capacity and capability to rapidly translate research evidence into health practice is critical to the effectiveness and sustainability of healthcare systems. This review scoped the literature describing programmes to build knowledge translation capacity and capability in health professionals and healthcare services, and the evidence supporting these. METHODS: This scoping review was undertaken using the Joanna Briggs Institute scoping review methodology. Four research databases (Ovid MEDLINE, CINAHL, Embase, and PsycInfo) were searched using a pre-determined strategy. Eligible studies described a programme implemented in healthcare settings to build health professional or healthcare service knowledge translation capacity and capability. Abstracts and full texts considered for inclusion were screened by two researchers. Data from included papers were extracted using a bespoke tool informed by the scoping review questions. RESULTS: Database searches yielded 10,509 unique citations, of which 136 full texts were reviewed. Thirty-four papers were included, with three additional papers identified on citation searching, resulting in 37 papers describing 34 knowledge translation capability building programmes. Programmes were often multifaceted, comprising a combination of two or more strategies including education, dedicated implementation support roles, strategic research-practice partnerships and collaborations, co-designed knowledge translation capability building programmes, and dedicated funding for knowledge translation. Many programmes utilised experiential and collaborative learning, and targeted either individual, team, organisational, or system levels of impact. Twenty-seven programmes were evaluated formally using one or more data collection methods. Outcomes measured varied significantly and included participant self-reported outcomes, perceived barriers and enablers of knowledge translation, milestone achievement and behaviour change. All papers reported that programme objectives were achieved to varying degrees. CONCLUSIONS: Knowledge translation capacity and capability building programmes in healthcare settings are multifaceted, often include education to facilitate experiential and collaborative learning, and target individual, team, organisational, or supra-organisational levels of impact. Although measured differently across the programmes, the outcomes were positive. The sustainability of programmes and outcomes may be undermined by the lack of long-term funding and inconsistent evaluation. Future research is required to develop evidence-informed frameworks to guide methods and outcome measures for short-, medium- and longer-term programme evaluation at the different structural levels.

Environmental Causes of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF), the most common and severe of the idiopathic interstitial pneumonias, is a chronic and relentlessly progressive disease, which occurs mostly in middle-aged and elderly males. Although IPF is by definition "idiopathic", multiple factors have been reported to increase disease risk, aging being the most prominent one. Several occupational and environmental exposures, including metal dust, wood dust and air pollution, as well as various lifestyle variables, including smoking and diet, have also been associated with an increased risk of IPF, probably through interaction with genetic factors. Many of the predisposing factors appear to act also as trigger for acute exacerbations of the disease, which herald a poor prognosis. The more recent literature on inhalation injuries has focused on the first responders in the World Trade Center attacks and military exposure. In this review, we present an overview of the environmental and occupational causes of IPF and its pathogenesis. While our list is not comprehensive, we have selected specific exposures to highlight based on their overall disease burden.

A qualitative system model to describe the causes and drivers of frequent potentially avoidable presentations to the emergency department.

Frequent potentially avoidable presentations to Emergency Departments (EDs) represent a complex problem, driven by multiple interdependent and interacting factors that change over time and influence one another. We sought to describe and map the drivers of frequent potentially avoidable presentations to a regional ED, servicing regional and rural areas, and identify possible solutions from the perspectives of key stakeholders. This study used a qualitative, community-based systems dynamics approach utilising Group Model Building (GMB). Data were collected from two 3-h online workshops embedded with small-group discussions and conducted with stakeholder groups operating within a regional health system. Stakeholders were guided through a series of participatory tasks to develop a causal loop diagram (CLD) using Systems Thinking in Community Knowledge Exchange software (n=29, workshop one), identify potential action points and generate a prioritised action list to intervene in the system (n=21, workshop two). Data were collected through note taking, real-time system mapping, and recording the workshops. Each action was considered against the Public Health 12 framework describing twelve leverage points to intervene in a system. A CLD illustrating the complex and interrelated factors that drive frequent potentially avoidable ED presentations was developed and classified into four categories: (1) access to services; (2) coordination; (3) patient needs; and (4) knowledge and skills. Nine action areas were identified, with many relating to care and service coordination. Most actions aligned with lower-level system impact actions. This study provides an in-depth understanding of influencing factors and potential solutions for frequent potentially avoidable ED presentations across a regional health system. The CLD demonstrates frequent potentially avoidable ED presentations are a complex problem and identified that a prevention response should engage with system- and individual-level solutions. Further work is needed to prioritise actions to support the implementation of higher-level system impacts.

Using Chronic Care Management Visits to Reduce the Number of Frequent Emergency Department Visits: A Pilot Study.

Background Emergency department (ED) visits are increasing in number and cost and becoming a major way patients are interacting with the healthcare system. Patients who frequently visit the ED are deemed "super-utilizers" who visit for a variety of reasons, including, but not limited to, multiple chronic medical illnesses, homelessness, and substance use disorder, but fail to have an established long-term treatment plan. Methodology We enrolled our hospital's top 50 super-utilizing patients into the Chronic Care Management Program. These patients received monthly telehealth visits to discuss concerns, chronic medical conditions, barriers to care, and support systems unique to each patient's living and social situation (i.e., social determinants of health). Telehealth visits also connected patients to community resources and helped them initiate advanced care services. Results The t-test investigating the frequency of avoidable visits pre- and post-intervention revealed a statistically significant decrease in the number of avoidable visits between the pre-intervention and post-intervention. Results also revealed a non-statistically significant difference in the cost of avoidable visits before and after the intervention. Conclusions The findings revealed a statistically significant decrease in patients' frequency of avoidable visits before and after the intervention.

Enhancing healthcare at home for older people in rural and regional Australia: A protocol for co-creation to design and implement system change.

BACKGROUND: World-wide, health service providers are moving towards innovative models of clinical home-based care services as a key strategy to improve equity of access and quality of care. To optimise existing and new clinical home-based care programs, evidence informed approaches are needed that consider the complexity of the health care system across different contexts. METHODS: We present a protocol for working with health services and their partners to perform rapid identification, prioritisation, and co-design of content-appropriate strategies to optimise the delivery of healthcare at home for older people in rural and regional areas. The protocol combines Systems Thinking and Implementation Science using a Consensus Mapping and Co-design (CMC) process delivered over five workshops. DISCUSSION: The protocol will be implemented with rural and regional healthcare providers to identify digital and non-digital solutions that have the potential to inform models of service delivery, improve patient experience, and optimise health outcomes. The combination of system and implementation science is a unique approach for optimising healthcare at home for older populations, especially in the rural context where need is high. This is the first protocol to integrate the use of systems and implementation science into one process and articulating these methods will help with replicating this in future practice. Results of the design phase will translate into practice through standard health service planning methods to enhance implementation and sustainability. The delivery of the protocol will include building capacity of health service workers to embed the design, implementation, and evaluation approach into normal practice. This protocol forms part of the DELIVER (Delivering Enhanced heaLthcare at home through optImising Virtual tools for oldEr people in Rural and regional Australia) Project. Funded by Australia's Medical Research Future Fund, DELIVER involves a collaboration with public health services of Western Victoria, Australia.

Sex-Linked Differences in Malaria Risk Across the Lifespan.

Despite the high burden of malaria worldwide, there is surprisingly scarce research on sex-based differences in malaria outside of pregnancy. A more thorough understanding of sexual dimorphism in malaria, and what underlies these sex-based differences, could elucidate the underlying mechanisms driving malaria pathogenesis and has the potential to inform malaria control efforts, including new vaccines. This review summarizes our current understanding of sex-based differences in the epidemiology of malaria across the lifespan, potential sex- or gender-based mechanisms driving these differences, and the knowledge gaps that need to be addressed.

Change in Caregiver Health-Related Quality of Life From Before to Early After Surgery: SUSTAIN-IT Study.

BACKGROUND: Information about health-related quality of life (HRQOL) among caregivers of older patients with heart failure who receive heart transplantation (HT) and mechanical circulatory support (MCS) is sparse. We describe differences and factors associated with change in HRQOL before and early post-surgery among caregivers of older heart failure patients who underwent 3 surgical therapies: HT with pretransplant MCS (HT MCS), HT without pretransplant MCS (HT non-MCS), and long-term MCS. METHODS: Caregivers of older patients (60-80 years) from 13 US sites completed the EQ-5D-3 L visual analog scale (0 [worst]-100 [best] imaginable health state) and dimensions before and 3 and 6 months post-surgery. Analyses included linear regression, t tests, and nonparametric tests. RESULTS: Among 227 caregivers (HT MCS=54, HT non-MCS=76, long-term MCS=97; median age 62.7 years, 30% male, 84% White, 83% spouse/partner), EQ-5D visual analog scale scores were high before (84.8±14.1) and at 3 (84.7±13.0) and 6 (83.9±14.7) months post-surgery, without significant differences among groups or changes over time. Patient pulmonary hypertension presurgery (ß=-13.72 [95% CI, -21.07 to -6.36]; P<0.001) and arrhythmia from 3 to 6 months post-operatively (ß=-14.22 [95% CI, -27.41 to -1.02]; P=0.035) were associated with the largest decrements in caregiver HRQOL; patient marital/partner status (ß=6.21 [95% CI, 1.34-11.08]; P=0.013) and presurgery coronary disease (ß=8.98 [95% CI, 4.07-13.89]; P<0.001) were associated with the largest improvements. CONCLUSIONS: Caregivers of older patients undergoing heart failure surgeries reported overall high HRQOL before and early post-surgery. Understanding factors associated with caregiver HRQOL may inform decision-making and support needs. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02568930.

A systematic review of the inhibitory effect of extracts from edible parts of nuts on α-glucosidase activity.

An elevated postprandial glycaemic response is a risk factor for developing type 2 diabetes mellitus (T2DM). Inhibition of digestive enzymes, including membrane-bound brush-border α-glucosidases, leads to slowed carbohydrate digestion and absorption, and reduced postprandial glycaemia. Nuts are eaten widely around the world, and have the potential to inhibit α-glucosidases through their content of polyphenols and other bioactive compounds. We set out to conduct a systematic literature review exploring the inhibitory effect of extracts from edible parts of various nuts on α-glucosidase activity in vitro to ensure, as far as possible, that no papers were missed. After an initial screening, 38 studies were reviewed in full, of which 15 were suitable for the present systematic review. Notably, no studies were found which tested the inhibitory potential of nut extracts against human α-glucosidases. Two studies showed that extracts from almonds and hazelnuts inhibited rat α-glucosidase activity, but the remaining papers reported data on the yeast α-glucosidase enzyme. Where yeast and rat enzymes can be compared, it is clear that nut extracts inhibit yeast α-glucosidase more strongly than mammalian α-glucosidase, which may lead to over-estimation when predicting effects in vivo when using data from the yeast enzyme. In contrast, acarbose is a stronger inhibitor of mammalian α-glucosidase compared to the yeast enzyme. Thus, although the present review indicates that extracts from nuts inhibit yeast α-glucosidase, this cannot be extrapolated to humans in vivo. There is some evidence that extracts from almonds and hazelnuts inhibit rat α-glucosidase, but no information on human enzyme sources. Since most work has been published on the yeast enzyme, future work in vitro must utilise mammalian, and preferably human, α-glucosidases in order to be relevant to human health and disease. This systematic review was registered at INPLASY as INPLASY202280061.

Caregiver burden before heart transplantation and long-term mechanical circulatory support: Findings from the sustaining quality of life of the aged: Transplant or mechanical support (SUSTAIN-IT) study.

BACKGROUND: Caregiving for heart failure (HF) patients is burdensome. We examined differences in caregiver burden for 3 groups of older advanced HF patients: (1) supported with mechanical circulatory support (MCS) before heart transplantation (HT MCS), (2) awaiting transplant without MCS (HT non-MCS), and (3) prior to long-term MCS and factors associated with burden. METHOD: From October 1, 2015 to December 31, 2018, we enrolled 276 caregivers for HF patients from 13 U.S. sites: 85 HT MCS, 96 HT non-MCS, and 95 prior to long-term MCS. At enrollment, caregivers completed the Oberst Caregiving Burden Scale (15 items, 2 subscales: time (range = 1-5; higher score = more time spent on task) and difficulty (range = 1-5; higher score = higher difficulty of task) and other measures. Statistical analyses included descriptive statistics, ANOVA, chi-square tests, and linear regression. RESULT: Overall, caregivers were aged 60.8 ± 9.8 years and predominantly white, female, spouses, well educated, and reported ≥1 comorbidities. Caregivers overall reported a moderate amount of time spent on tasks and slight task difficulty. Caregivers for HT non-MCS candidates reported significantly less perceived time spent on tasks than caregivers for HT MCS candidates and caregivers for patients prior to long-term MCS (2.2 ± 0.74 vs 2.4 ± 0.74 vs 2.5 ± 0.71, respectively, p = 0.02) and less perceived difficulty of tasks (1.2 ± 0.33 vs 1.4 ± 0.53 vs 1.4 ± 0.54, respectively, p = 0.01). Caregiver and patient factors were associated with caregiver burden. CONCLUSIONS: Prior to HT and long-term MCS, caregiver burden was low to moderate. Caregiver factors were predominantly associated with caregiver burden. Understanding caregiver burden and factors affecting caregiver burden may enhance preoperative advanced therapies discussions and guide caregiver support.

Demonstrating a link between diet, gut microbiota and brain: 14C radioactivity identified in the brain following gut microbial fermentation of 14C-radiolabeled tyrosine in a pig model.

Background: There is a need to better understand the relationship between the diet, the gut microbiota and mental health. Metabolites produced when the human gut microbiota metabolize amino acids may enter the bloodstream and have systemic effects. We hypothesize that fermentation of amino acids by a resistant protein-primed gut microbiota could yield potentially toxic metabolites and disturb the availability of neurotransmitter precursors to the brain. However, these mechanisms are challenging to investigate via typical in vitro and clinical methods. Methods: We developed a novel workflow using 14C radiolabeling to investigate complex nutrient-disease relationships. The first three steps of the workflow are reported here. α-Linolenic acid (ALA) was used as a model nutrient to confirm the efficacy of the workflow, and tyrosine (Tyr) was the test nutrient. 14C-Tyr was administered to male weanling pigs fed a high resistant protein diet, which primed the gut microbiota for fermenting protein. The hypotheses were; (1) that expected biodistribution of 14C-ALA would be observed, and (2) that radioactivity from 14C-Tyr, representing Tyr and other amino acids released from resistant protein following gut microbial fermentation, would be bioavailable to the brain. Results: Radioactivity from the 14C-ALA was detected in tissues reflecting normal utilization of this essential fatty acid. Radioactivity from the 14C-Tyr was detected in the brain (0.15% of original dose). Conclusion: Metabolites of gut-fermented protein and specifically amino acid precursors to neurotransmitters such as tyrosine, are potentially able to affect brain function. By extension, resistant proteins in the diet reaching the gut microbiota, also have potential to release metabolites that can potentially affect brain function. The high specificity of detection of 14C radioactivity demonstrates that the proposed workflow can similarly be applied to understand other key diet and health paradigms.

Health-Related Quality of Life in Older Patients With Heart Failure From Before to Early After Advanced Surgical Therapies: Findings From the SUSTAIN-IT Study.

BACKGROUND: Restoring health-related quality of life (HRQOL) is a therapeutic goal for older patients with advanced heart failure. We aimed to describe change in HRQOL in older patients (60-80 years) awaiting heart transplantation (HT) with or without pretransplant mechanical circulatory support (MCS) or scheduled for long-term MCS, if ineligible for HT, from before to 6 months after these surgeries and identify factors associated with change. METHODS: Patients from 13 US sites completed the EuroQol 5-dimension 3L questionnaire and Kansas City Cardiomyopathy Questionnaire-12 at baseline and 3 and 6 months after HT or long-term MCS. Analyses included univariate comparisons and multivariable linear regression. RESULTS: Among 305 participants (cohort mean age=66.2±4.7 years, 78% male, 84% White, 55% New York Heart Association class IV), 161 underwent HT (n=68 with and n=93 without pretransplant MCS), and 144 received long-term MCS. From baseline to 3 months, EuroQol 5-dimension visual analog scale scores improved in HT patients without pretransplant MCS (54.5±24.3 versus 75.9±16.0, P<0.001) and long-term MCS patients (45.7±22.9 versus 66.2± 20.9, P <0.001); while Kansas City Cardiomyopathy Questionnaire-12 overall summary scores improved in all 3 groups (HT without pretransplant MCS: 47.2±20.9 versus 77.4±20.1, P <0.001; long-term MCS: 35.3±20.2 versus 58.6±22.0, P <0.001; and HT with pretransplant MCS: 58.3±23.6 versus 72.1±23.5, P=0.002). No further HRQOL improvement was found from 3 to 6 months. Factors most significantly associated with change in HRQOL, baseline 3 months, were right heart failure and 3-month New York Heart Association class, and 3 to 6 months, were 6-month New York Heart Association class and major bleeding. CONCLUSIONS: In older heart failure patients, HRQOL improved from before to early after HT and long-term MCS. At 6 postoperative months, HRQOL of long-term MCS patients was lower than one or both HT groups. Understanding change in HRQOL from before to early after these surgeries may enhance decision-making and guide patient care. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02568930.

Should antidiabetic medicines be considered to reduce cardiometabolic risk in patients with serious mental illness?

Substantially reduced life expectancy for people with serious mental illness compared with the general population is primarily driven by physical health issues, of which cardiovascular disease is the leading cause. In this narrative review, we examine the evidence base for use of metformin and other antidiabetic agents as a means for reducing this excess cardiometabolic disease burden. Evidence from randomised controlled trials (RCTs) suggests substantial potential for metformin to prevent or manage weight gain and glycaemic impairment induced by atypical antipsychotic medications, whereas the impact of metformin on other cardiometabolic risk factors is less consistent. Evidence from RCTs also suggests potential benefits from glucagon-like peptide-1 receptor agonists (GLP-1RAs), particularly for addressing cardiometabolic risk factors in people using atypical antipsychotic medications, but this is based on a small number of trials and remains an emerging area of research. Trials of both metformin and GLP-1RAs suggest that these medications are associated with a high prevalence of mild-moderate gastrointestinal side effects. The heterogeneous nature of participant eligibility criteria and of antipsychotic and antidiabetic drug regimens, alongside short trial durations, small numbers of participants and paucity of clinical endpoints as trial outcomes, warrants investment in definitive trials to determine clinical benefits for both metformin and GLP-1RAs. Such trials would also help to confirm the safety profile of antidiabetic agents with respect to less common but serious adverse effects. The weight of RCT evidence suggests that an indication for metformin to address antipsychotic-induced weight gain is worth considering in Australia. This would bring us into line with other countries.

Reduced Growth, Altered Gut Microbiome and Metabolite Profile, and Increased Chronic Kidney Disease Risk in Young Pigs Consuming a Diet Containing Highly Resistant Protein.

High-heat processed foods contain proteins that are partially resistant to enzymatic digestion and pass through to the colon. The fermentation of resistant proteins by gut microbes produces products that may contribute to chronic disease risk. This pilot study examined the effects of a resistant protein diet on growth, fecal microbiome, protein fermentation metabolites, and the biomarkers of health status in pigs as a model of human digestion and metabolism. Weanling pigs were fed with standard or resistant protein diets for 4 weeks. The resistant protein, approximately half as digestible as the standard protein, was designed to enter the colon for microbial fermentation. Fecal and blood samples were collected to assess the microbiome and circulating metabolites and biomarkers. The resistant protein diet group consumed less feed and grew to ~50% of the body mass of the standard diet group. The diets had unique effects on the fecal microbiome, as demonstrated by clustering in the principal coordinate analysis. There were 121 taxa that were significantly different between groups (adjusted-p < 0.05). Compared with control, plasma tri-methylamine-N-oxide, homocysteine, neopterin, and tyrosine were increased and plasma acetic acid was lowered following the resistant protein diet (all p < 0.05). Compared with control, estimated glomerular filtration rate (p < 0.01) and liver function marker aspartate aminotransferase (p < 0.05) were also lower following the resistant protein diet. A resistant protein diet shifted the composition of the fecal microbiome. The microbial fermentation of resistant protein affected the levels of circulating metabolites and the biomarkers of health status toward a profile indicative of increased inflammation and the risk of chronic kidney disease.

Co-ordinated multidisciplinary intervention to reduce time to successful extubation for children on mechanical ventilation: the SANDWICH cluster stepped-wedge RCT.

BACKGROUND: Daily assessment of patient readiness for liberation from invasive mechanical ventilation can reduce the duration of ventilation. However, there is uncertainty about the effectiveness of this in a paediatric population. OBJECTIVES: To determine the effect of a ventilation liberation intervention in critically ill children who are anticipated to have a prolonged duration of mechanical ventilation (primary objective) and in all children (secondary objective). DESIGN: A pragmatic, stepped-wedge, cluster randomised trial with economic and process evaluations. SETTING: Paediatric intensive care units in the UK. PARTICIPANTS: Invasively mechanically ventilated children (aged < 16 years). INTERVENTIONS: The intervention incorporated co-ordinated multidisciplinary care, patient-relevant sedation plans linked to sedation assessment, assessment of ventilation parameters with a higher than usual trigger for undertaking an extubation readiness test and a spontaneous breathing trial on low levels of respiratory support to test extubation readiness. The comparator was usual care. Hospital sites were randomised sequentially to transition from control to intervention and were non-blinded. MAIN OUTCOME MEASURES: The primary outcome measure was the duration of invasive mechanical ventilation until the first successful extubation. The secondary outcome measures were successful extubation, unplanned extubation and reintubation, post-extubation use of non-invasive ventilation, tracheostomy, post-extubation stridor, adverse events, length of intensive care and hospital stay, mortality and cost per respiratory complication avoided at 28 days. RESULTS: The trial included 10,495 patient admissions from 18 paediatric intensive care units from 5 February 2018 to 14 October 2019. In children with anticipated prolonged ventilation (n = 8843 admissions: control, n = 4155; intervention, n = 4688), the intervention resulted in a significantly shorter time to successful extubation [cluster and time-adjusted median difference -6.1 hours (interquartile range -8.2 to -5.3 hours); adjusted hazard ratio 1.11, 95% confidence interval 1.02 to 1.20; p = 0.02] and a higher incidence of successful extubation (adjusted relative risk 1.01, 95% confidence interval 1.00 to 1.02; p = 0.03) and unplanned extubation (adjusted relative risk 1.62, 95% confidence interval 1.05 to 2.51; p = 0.03), but not reintubation (adjusted relative risk 1.10, 95% confidence interval 0.89 to 1.36; p = 0.38). In the intervention period, the use of post-extubation non-invasive ventilation was significantly higher (adjusted relative risk 1.22, 95% confidence interval 1.01 to 1.49; p = 0.04), with no evidence of a difference in intensive care length of stay or other harms, but hospital length of stay was longer (adjusted hazard ratio 0.89, 95% confidence interval 0.81 to 0.97; p = 0.01). Findings for all children were broadly similar. The control period was associated with lower, but not statistically significantly lower, total costs (cost difference, mean £929.05, 95% confidence interval -£516.54 to £2374.64) and significantly fewer respiratory complications avoided (mean difference -0.10, 95% confidence interval -0.16 to -0.03). LIMITATIONS: The unblinded intervention assignment may have resulted in performance or detection bias. It was not possible to determine which components were primarily responsible for the observed effect. Treatment effect in a more homogeneous group remains to be determined. CONCLUSIONS: The intervention resulted in a statistically significant small reduction in time to first successful extubation; thus, the clinical importance of the effect size is uncertain. FUTURE WORK: Future work should explore intervention sustainability and effects of the intervention in other paediatric populations. TRIAL REGISTRATION: This trial is registered as ISRCTN16998143. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 18. See the NIHR Journals Library website for further project information.

Mechanical ventilation is a life-saving therapy, but may involve related risks because of the breathing tube in the mouth and throat, the sedative drugs required to reduce anxiety and remaining confined to bed. Therefore, getting off the ventilator (called weaning) is an important patient outcome. Previous studies have shown that an organised approach involving nurses, doctors and physiotherapists reduces the time that patients spend on the ventilator. Our study involved more than 10,000 patients admitted to 18 children's intensive care units. We tested a co-ordinated staff approach for managing a child's sedation and ventilator needs against usual care, which was mainly consultant led and did not involve bedside nurses. We wanted to find out if this approach improved the outcomes for children and did not cause additional harm. We first collected information in the intensive care units when children were weaned from the ventilator using usual care. Following staff training in the new approach, we compared children's outcomes between the two approaches. Compared with usual care, the new approach reduced the time that children spent on the ventilator by between 5 and 9 hours, and increased children's chances of having their breathing tube removed successfully. Some children pulled out their breathing tubes themselves before it was medically planned to do so. This happened more with the new approach, but the chance of needing the breathing tube put back in was not different from usual care. With the new approach, more children needed to use a mask ventilator than those receiving usual care, although the length of time that this was required was not different from usual care. The intensive care length of stay was the same for children receiving the new approach and usual care. However, with the new approach, children stayed in hospital 1 day longer, which resulted in higher costs (£715 per child); thus, the clinical relevance is uncertain.

Health-Related Quality of Life in Older Patients With Advanced Heart Failure: Findings From the SUSTAIN-IT Study.

Background There is a paucity of research describing health-related quality of life (HRQOL) in older adults considered for advanced heart failure surgical therapies. Using data from our SUSTAIN-IT (Sustaining Quality of Life of the Aged: Heart Transplant or Mechanical Support) study, we aimed to compare HRQOL among 3 groups of older (60-80 years) patients with heart failure before heart transplantation (HT) or long-term mechanical circulatory support (MCS) and identify factors associated with HRQOL: (1) HT candidates with MCS, (2) HT candidates without MCS, or (3) candidates ineligible for HT and scheduled for long-term MCS. Methods and Results Patients from 13 US sites completed assessments, including self-reported measures of HRQOL (EuroQol-5 Dimension Questionnaire, Kansas City Cardiomyopathy Questionnaire-12), depressive symptoms (Personal Health Questionnaire-8), anxiety (State-Trait Anxiety Inventory-state form), cognitive status (Montreal Cognitive Assessment), and performance-based measures (6-minute walk test and 5-m gait speed). Analyses included ANOVA, χ2 tests, Fisher's exact tests, and linear regression. The sample included 393 patients; the majority of patients were White men and married. Long-term MCS candidates (n=154) were significantly older and had more comorbidities and a higher New York Heart Association class than HT candidates with MCS (n=118) and HT candidates without MCS (n=121). Long-term MCS candidates had worse HRQOL than HT candidates with and without MCS (EQ-5D visual analog scale scores, 46±23 versus 68±18 versus 54±23 [P<0.001] and Kansas City Cardiomyopathy Questionnaire-12 overall summary scores, 35±21 versus 60±21 versus 49±22 [P<0.001], respectively). In multivariable analyses, lower 6-minute walk distance, higher New York Heart Association class, depressive symptoms, and not being an HT candidate with MCS were significantly associated with worse overall HRQOL. Conclusions Our findings demonstrate important differences in overall and domain-specific HRQOL of older patients with heart failure before HT or long-term MCS. Understanding HRQOL differences may guide decisions toward more appropriate and personalized advanced heart failure therapies.

Does timing of phytonutrient intake influence the suppression of postprandial oxidative stress? A systematic literature review.

BACKGROUND: Postprandial oxidative stress markers in blood are generated transiently from various tissues and cells following high-fat and/or high-carbohydrate (HFHC) meals, and may be suppressed by certain phytonutrients, such as polyphenols and carotenoids. However, the transient presence of phytonutrients in circulation suggests that timing of consumption, relative to the meal, could be important. This systematic review investigates the effect of timing of phytonutrient intake on blood markers of postprandial oxidative processes. METHOD: EMBASE, Medline, Scopus and Web of Science were searched up to December 2020. Eligible studies met the criteria: 1) healthy human adults; 2) phytonutrient(s) consumed in solid form within 24 h of a HFHC meal; 3) postprandial measurements of oxidative stress or antioxidants in blood; and 4) controlled study design. Cohen's d effect sizes were calculated to compare studies. RESULTS: Nine studies, involving 256 participants, were included. Phytonutrients were consumed either at the same time, 1 h before, or the day (>12 h) before a HFHC meal. Significant decreases in blood markers - plasma lipid hydroperoxides, plasma malondialdehyde, serum sNox2-dp, serum 8-iso-PGF2α, platelet p47phox phosphorylation, and Keap-1 and p47phox protein levels in mononuclear cells (MNCs) - were observed where the phytonutrient was consumed together with the challenge meal (n = 4). Lack of any effect on oxidative stress markers was observed where phytonutrients were consumed with (n = 1), 1 h before (n = 1), and the day before (n = 2) the HFHC meal. CONCLUSION: Phytonutrients consumed with a HFHC meal significantly suppressed some markers of oxidative stress in blood. Although there were only a limited number of studies, it appears that suppression appeared effective at the time of peak phytonutrient concentration in plasma. However, further studies are required to confirm the observations and systematically optimise the effect of timing.

Effect of a Sedation and Ventilator Liberation Protocol vs Usual Care on Duration of Invasive Mechanical Ventilation in Pediatric Intensive Care Units: A Randomized Clinical Trial.

Importance: There is limited evidence on the optimal strategy for liberating infants and children from invasive mechanical ventilation in the pediatric intensive care unit. Objective: To determine if a sedation and ventilator liberation protocol intervention reduces the duration of invasive mechanical ventilation in infants and children anticipated to require prolonged mechanical ventilation. Design, Setting, and Participants: A pragmatic multicenter, stepped-wedge, cluster randomized clinical trial was conducted that included 17 hospital sites (18 pediatric intensive care units) in the UK sequentially randomized from usual care to the protocol intervention. From February 2018 to October 2019, 8843 critically ill infants and children anticipated to require prolonged mechanical ventilation were recruited. The last date of follow-up was November 11, 2019. Interventions: Pediatric intensive care units provided usual care (n = 4155 infants and children) or a sedation and ventilator liberation protocol intervention (n = 4688 infants and children) that consisted of assessment of sedation level, daily screening for readiness to undertake a spontaneous breathing trial, a spontaneous breathing trial to test ventilator liberation potential, and daily rounds to review sedation and readiness screening and set patient-relevant targets. Main Outcomes and Measures: The primary outcome was the duration of invasive mechanical ventilation from initiation of ventilation until the first successful extubation. The primary estimate of the treatment effect was a hazard ratio (with a 95% CI) adjusted for calendar time and cluster (hospital site) for infants and children anticipated to require prolonged mechanical ventilation. Results: There were a total of 8843 infants and children (median age, 8 months [interquartile range, 1 to 46 months]; 42% were female) who completed the trial. There was a significantly shorter median time to successful extubation for the protocol intervention compared with usual care (64.8 hours vs 66.2 hours, respectively; adjusted median difference, -6.1 hours [interquartile range, -8.2 to -5.3 hours]; adjusted hazard ratio, 1.11 [95% CI, 1.02 to 1.20], P = .02). The serious adverse event of hypoxia occurred in 9 (0.2%) infants and children for the protocol intervention vs 11 (0.3%) for usual care; nonvascular device dislodgement occurred in 2 (0.04%) vs 7 (0.1%), respectively. Conclusions and Relevance: Among infants and children anticipated to require prolonged mechanical ventilation, a sedation and ventilator liberation protocol intervention compared with usual care resulted in a statistically significant reduction in time to first successful extubation. However, the clinical importance of the effect size is uncertain. Trial Registration: isrctn.org Identifier: ISRCTN16998143.

Twelve weeks' treatment with a polyphenol-rich seaweed extract increased HDL cholesterol with no change in other biomarkers of chronic disease risk in overweight adults: A placebo-controlled randomized trial.

Cardiovascular diseases (CVD) are the leading global cause of death. Strategies to reduce CVD risk are urgently needed. Polyphenols represent a class of bioactive compounds with potential to moderate biochemical risk factors for CVD (cholesterol, triglycerides, glucose, and inflammation). This double-blind, placebo-controlled, randomized parallel-groups trial investigated the effect of a polyphenol-rich seaweed (Fucus vesiculosus) extract on biochemical markers of CVD risk. Thirty-four overweight and obese adults (21 female, 13 male) with elevated low-density lipoprotein cholesterol (>2.0 mmol/L) were randomized to either the seaweed extract (2000 mg/d) or placebo for twelve weeks. Fasting blood samples were collected at baseline, week six and week twelve to assess biochemical markers. Tests of cognitive performance and mood were performed at baseline, week six and week twelve. A 9.5% (-2.3, 12.9) increase in high-density lipoprotein (HDL) cholesterol was identified following the seaweed extract (baseline: mean (SD) 1.28 (0.23) mmol/L, week 12: 1.35 (0.24) mmol/L) which was different to placebo (baseline: 1.38 (0.54) mmol/L, week 12: 1.35 (0.59) mmol/L) (P=.045). No changes were identified in low-density lipoprotein cholesterol, total cholesterol, triglycerides, glucose, insulin, interleukin (IL)-2, IL-6, IL-8, IL-10, or tumour necrosis factor-alpha levels in the blood, or in cognitive performance or mood between the treatment and placebo groups. Despite the small increase observed in HDL cholesterol, the polyphenol-rich seaweed extract did not change CVD risk factors in adults with high fasting lipids. A larger sample size would be required to confirm the clinical relevance of the changes in HDL cholesterol.

Profile of Mothers of Children with Fetal Alcohol Spectrum Disorder: A Population-Based Study in Canada.

OBJECTIVE: To compare the characteristics of mothers of children with Fetal Alcohol Spectrum Disorder (FASD) with mothers of typically developing control children. METHODS: The study utilized a cross-sectional, observational design, using active case ascertainment. Biological mothers were interviewed using a standardized retrospective questionnaire to collect data on demographics, living environment, pregnancy history, nutrition, alcohol and other drug use prior to and following pregnancy recognition. RESULTS: A total of 173 mothers were interviewed. Of these, 19 had a child who was diagnosed with FASD, five had a child who had received a deferred FASD diagnosis, and 37 had children who were selected into the control group as typically developing children. The remaining 112 mothers had children who did not meet diagnostic criteria for FASD. The mothers of children with FASD did not differ significantly from mothers of the control group children with respect to age, ethnicity, marital status, and employment status at the time of pregnancy. However, mothers of children with FASD had lower levels of education (p < 0.01) and were more likely to have received financial support (p < 0.05) at the time of pregnancy, to have smoked tobacco (p < 0.001), and to have used marijuana or hashish (p < 0.01) prior to pregnancy recognition, compared with mothers of control children. All mothers of children with FASD reported alcohol consumption prior to pregnancy recognition; however, only 10.5% reported alcohol consumption following pregnancy recognition. None of the mothers interviewed reported any drug use following pregnancy recognition. CONCLUSIONS: Population-based preventive interventions, including repeated screening, monitoring, and education regarding the effects of alcohol use, as well as other substances, before and during pregnancy, are needed to eliminate risk for FASD and other negative consequences on child and maternal health.

Sex-based differences in clearance of chronic Plasmodium falciparum infection.

Multiple studies have reported a male bias in incidence and/or prevalence of malaria infection in males compared to females. To test the hypothesis that sex-based differences in host-parasite interactions affect the epidemiology of malaria, we intensively followed Plasmodium falciparum infections in a cohort in a malaria endemic area of eastern Uganda and estimated both force of infection (FOI) and rate of clearance using amplicon deep-sequencing. We found no evidence of differences in behavioral risk factors, incidence of malaria, or FOI by sex. In contrast, females cleared asymptomatic infections at a faster rate than males (hazard ratio [HR]=1.82, 95% CI 1.20 to 2.75 by clone and HR = 2.07, 95% CI 1.24 to 3.47 by infection event) in multivariate models adjusted for age, timing of infection onset, and parasite density. These findings implicate biological sex-based differences as an important factor in the host response to this globally important pathogen.