Patient, caregiver and other knowledge user engagement in consensus-building healthcare initiatives: a scoping review protocol.

INTRODUCTION: Patient engagement and integrated knowledge translation (iKT) processes improve health outcomes and care experiences through meaningful partnerships in consensus-building initiatives and research. Consensus-building is essential for engaging a diverse group of experienced knowledge users in co-developing and supporting a solution where none readily exists or is less optimal. Patients and caregivers provide invaluable insights for building consensus in decision-making around healthcare, policy and research. However, despite emerging evidence, patient engagement remains sparse within consensus-building initiatives. Specifically, our research has identified a lack of opportunity for youth living with chronic health conditions and their caregivers to participate in developing consensus on indicators/benchmarks for transition into adult care. To bridge this gap and inform our consensus-building approach with youth/caregivers, this scoping review will synthesise the extent of the literature on patient and other knowledge user engagement in consensus-building healthcare initiatives. METHODS AND ANALYSIS: Following the scoping review methodology from Joanna Briggs Institute, published literature will be searched in MEDLINE, EMBASE, CINAHL and PsycINFO databases from inception to July 2023. Grey literature will be hand-searched. Two independent reviewers will determine the eligibility of articles in a two-stage process, with disagreements resolved by a third reviewer. Included studies must be consensus-building studies within the healthcare context that involve patient engagement strategies. Data from eligible studies will be extracted and charted on a standardised form. Abstracted data will be analysed quantitatively and descriptively, according to specific consensus methodologies, and patient engagement models and/or strategies. ETHICS AND DISSEMINATION: Ethics approval is not required for this scoping review protocol. The review process and findings will be shared with and informed by relevant knowledge users. Dissemination of findings will also include peer-reviewed publications and conference presentations. The results will offer new insights for supporting patient engagement in consensus-building healthcare initiatives. PROTOCOL REGISTRATION: https://osf.io/beqjr.

Inappropriate Use of Peripherally Inserted Central Catheters in Pediatrics: A Multisite Study.

OBJECTIVES: This study aimed to describe how the current practice of peripherally inserted central catheter (PICC) use in hospitalized children aligns with the Michigan Appropriateness Guide for Intravenous Catheters (miniMAGIC) in Children recommendations, explore variation across sites, and describe the population of children who do not receive appropriate PICCs. METHODS: A retrospective study was conducted at 4 children's hospitals in the United States. Children with PICCs placed January 2019 to December 2021 were included. Patients in the NICU were excluded. PICCs were categorized using the miniMAGIC in Children classification as inappropriate, uncertain appropriateness and appropriate. RESULTS: Of the 6051 PICCs identified, 9% (n = 550) were categorized as inappropriate, 9% (n = 550) as uncertain appropriateness, and 82% (n = 4951) as appropriate. The number of PICCs trended down over time, but up to 20% of PICCs each year were not appropriate, with significant variation between sites. Within inappropriate or uncertain appropriateness PICCs (n = 1100 PICC in 1079 children), median (interquartile range) patient age was 4 (0-11) years, 54% were male, and the main reason for PICC placement was prolonged antibiotic course (56%, n = 611). The most common admitting services requesting the inappropriate/uncertain appropriateness PICCs were critical care 24%, general pediatrics 22%, and pulmonary 20%. Complications resulting in PICC removal were identified in 6% (n = 70) of inappropriate/uncertain PICCs. The most common complications were dislodgement (3%) and occlusion (2%), with infection and thrombosis rates of 1% (n = 10 and n = 13, respectively). CONCLUSIONS: Although the majority of PICCs met appropriateness criteria, a substantial proportion of PICCs were deemed inappropriate or of uncertain appropriateness, illustrating an opportunity for quality improvement.

Social and Structural Drivers of Health and Transition to Adult Care.

CONTEXT: Youth with chronic health conditions experience challenges during their transition to adult care. Those with marginalized identities likely experience further disparities in care as they navigate structural barriers throughout transition. OBJECTIVES: This scoping review aims to identify the social and structural drivers of health (SSDOH) associated with outcomes for youth transitioning to adult care, particularly those who experience structural marginalization, including Black, Indigenous, and 2-spirit, lesbian, gay, bisexual, transgender, queer or questioning, and others youth. DATA SOURCES: Medline, Embase, CINAHL, and PsycINFO were searched from earliest available date to May 2022. STUDY SELECTION: Two reviewers screened titles and abstracts, followed by full-text. Disagreements were resolved by a third reviewer. Primary research studying the association between SSDOH and transition outcomes were included. DATA EXTRACTION: SSDOH were subcategorized as social drivers, structural drivers, and demographic characteristics. Transition outcomes were classified into themes. Associations between SSDOH and outcomes were assessed according to their statistical significance and were categorized into significant (P < .05), nonsignificant (P > .05), and unclear significance. RESULTS: 101 studies were included, identifying 12 social drivers (childhood environment, income, education, employment, health literacy, insurance, geographic location, language, immigration, food security, psychosocial stressors, and stigma) and 5 demographic characteristics (race and ethnicity, gender, illness type, illness severity, and comorbidity). No structural drivers were studied. Gender was significantly associated with communication, quality of life, transfer satisfaction, transfer completion, and transfer timing, and race and ethnicity with appointment keeping and transfer completion. LIMITATIONS: Studies were heterogeneous and a meta-analysis was not possible. CONCLUSIONS: Gender and race and ethnicity are associated with inequities in transition outcomes. Understanding these associations is crucial in informing transition interventions and mitigating health inequities.

Phages overcome bacterial immunity via diverse anti-defence proteins.

It was recently shown that bacteria use, apart from CRISPR-Cas and restriction systems, a considerable diversity of phage resistance systems1-4, but it is largely unknown how phages cope with this multilayered bacterial immunity. Here we analysed groups of closely related Bacillus phages that showed differential sensitivity to bacterial defence systems, and discovered four distinct families of anti-defence proteins that inhibit the Gabija, Thoeris and Hachiman systems. We show that these proteins Gad1, Gad2, Tad2 and Had1 efficiently cancel the defensive activity when co-expressed with the respective defence system or introduced into phage genomes. Homologues of these anti-defence proteins are found in hundreds of phages that infect taxonomically diverse bacterial species. We show that the anti-Gabija protein Gad1 blocks the ability of the Gabija defence complex to cleave phage-derived DNA. Our data further reveal that the anti-Thoeris protein Tad2 is a 'sponge' that sequesters the immune signalling molecules produced by Thoeris TIR-domain proteins in response to phage infection. Our results demonstrate that phages encode an arsenal of anti-defence proteins that can disable a variety of bacterial defence mechanisms.

Structural basis of Gabija anti-phage defence and viral immune evasion.

Bacteria encode hundreds of diverse defence systems that protect them from viral infection and inhibit phage propagation1-5. Gabija is one of the most prevalent anti-phage defence systems, occurring in more than 15% of all sequenced bacterial and archaeal genomes1,6,7, but the molecular basis of how Gabija defends cells from viral infection remains poorly understood. Here we use X-ray crystallography and cryo-electron microscopy (cryo-EM) to define how Gabija proteins assemble into a supramolecular complex of around 500 kDa that degrades phage DNA. Gabija protein A (GajA) is a DNA endonuclease that tetramerizes to form the core of the anti-phage defence complex. Two sets of Gabija protein B (GajB) dimers dock at opposite sides of the complex and create a 4:4 GajA-GajB assembly (hereafter, GajAB) that is essential for phage resistance in vivo. We show that a phage-encoded protein, Gabija anti-defence 1 (Gad1), directly binds to the Gabija GajAB complex and inactivates defence. A cryo-EM structure of the virally inhibited state shows that Gad1 forms an octameric web that encases the GajAB complex and inhibits DNA recognition and cleavage. Our results reveal the structural basis of assembly of the Gabija anti-phage defence complex and define a unique mechanism of viral immune evasion.

Thoracic Society of Australia and New Zealand (TSANZ) position statement on chronic suppurative lung disease and bronchiectasis in children, adolescents and adults in Australia and New Zealand.

This position statement, updated from the 2015 guidelines for managing Australian and New Zealand children/adolescents and adults with chronic suppurative lung disease (CSLD) and bronchiectasis, resulted from systematic literature searches by a multi-disciplinary team that included consumers. The main statements are: Diagnose CSLD and bronchiectasis early; this requires awareness of bronchiectasis symptoms and its co-existence with other respiratory diseases (e.g., asthma, chronic obstructive pulmonary disease). Confirm bronchiectasis with a chest computed-tomography scan, using age-appropriate protocols and criteria in children. Undertake a baseline panel of investigations. Assess baseline severity, and health impact, and develop individualized management plans that include a multi-disciplinary approach and coordinated care between healthcare providers. Employ intensive treatment to improve symptom control, reduce exacerbation frequency, preserve lung function, optimize quality-of-life and enhance survival. In children, treatment also aims to optimize lung growth and, when possible, reverse bronchiectasis. Individualize airway clearance techniques (ACTs) taught by respiratory physiotherapists, encourage regular exercise, optimize nutrition, avoid air pollutants and administer vaccines following national schedules. Treat exacerbations with 14-day antibiotic courses based upon lower airway culture results, local antibiotic susceptibility patterns, clinical severity and patient tolerance. Patients with severe exacerbations and/or not responding to outpatient therapy are hospitalized for further treatments, including intravenous antibiotics and intensive ACTs. Eradicate Pseudomonas aeruginosa when newly detected in lower airway cultures. Individualize therapy for long-term antibiotics, inhaled corticosteroids, bronchodilators and mucoactive agents. Ensure ongoing care with 6-monthly monitoring for complications and co-morbidities. Undertake optimal care of under-served peoples, and despite its challenges, delivering best-practice treatment remains the overriding aim.

The Utility and Acceptability of a New Noninvasive Ventilatory Assist Device, Rest-Activity Cycler-Positive Airways Pressure, During Exercise in a Population of Healthy Adults: Cohort Study.

BACKGROUND: Noninvasive ventilation has been demonstrated to benefit people who have moderate to severe chronic obstructive pulmonary disease during acute exacerbations. Studies have begun to investigate the effectiveness of noninvasive ventilation during pulmonary rehabilitation to improve outcomes for people with chronic obstructive pulmonary disease; however, the lack of portability and humidification of these devices means their use is limited, especially when performing activities of daily living. A new prototype device, RACer-PAP (rest-activity cycler-positive airways pressure), delivers battery-operated positive airway pressure via a nasal interface while regulating nasal airway apportionment bias, removing the need for supplementary humidification. This device may offer people with chronic obstructive pulmonary disease an improved ability to participate in pulmonary rehabilitation and activities of daily living. OBJECTIVE: To assess the feasibility of exercising with the RACer-PAP in situ and the acceptability of the device during exercise in normal, healthy individuals. METHODS: A total of 15 healthy adults were invited to attend 2 exercise sessions, each 1 week apart. Sessions lasted approximately 1 hour and included 2 baseline 6-minute walk distance assessments, once with and once without the RACer-PAP in situ. Vital signs and spirometry results were monitored throughout, and spirometry was performed pre- and posttesting with RACer-PAP. Subjective questionnaires ascertained participant feedback on exercising with the device in situ. RESULTS: Of the 15 initial participants, 14 (93%) completed both sessions. There were no adverse events associated with exercising with the device in situ. There were no differences in vital signs or 6-minute walk distance whether exercising with or without the device in situ. There were small increases in maximum dyspnea score (on the Borg scale) when exercising with the device in situ (median score 2.0, IQR 0.5-3.0, vs 3.0, IQR 2.0-3.25). There were small increases in forced vital capacity following exercise with the RACer-PAP. None of the participants reported symptoms associated with airway drying. Participant feedback provided recommendations for modifications for the next iteration of the device prior to piloting the device with people with chronic obstructive pulmonary disease. CONCLUSIONS: This study has shown RACer-PAP to be safe and feasible to use during exercise and has provided feedback for modifications to the device to improve its use during exercise. We now propose to consider the application of the device in a small pilot feasibility study to assess the safety, feasibility, and utility of the device in a population of people with moderate to severe chronic obstructive pulmonary disease. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12619000478112; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375477.

Sputum procalcitonin: a potential biomarker in stable bronchiectasis.

Sputum procalcitonin is elevated in exacerbations of bronchiectasis. The primary aim of this study was to investigate whether sputum procalcitonin levels are higher in patients with stable bronchiectasis than in healthy controls. We also assessed differences in procalcitonin levels in spontaneously expectorated and induced sputum samples and their repeatability 1 week later. Participants included were aged over 18 years and either had radiologically confirmed bronchiectasis or were healthy controls. Patients with bronchiectasis were clinically stable for at least 6 weeks and had spontaneous and induced sputum collected at visit 1 and again 7 days later. Only induced sputum samples were collected from healthy controls during visit 1. Sputum procalcitonin concentrations in sputum were measured. In total, 30 patients with bronchiectasis and 15 healthy controls were enrolled in this observational study. In the pooled data from visit 1 and 2, the geometric mean procalcitonin level in induced sputum was significantly higher in the bronchiectasis group than in the healthy control group (1.5 ng·mL-1, 95% CI 1.0-2.1 ng·mL-1 versus 0.4 ng·mL-1, 95% CI 0.2-0.9 ng·mL-1; mean ratio 3.6, 95% CI 1.5-8.6; p=0.006). Mean procalcitonin level was higher in spontaneous sputum than in induced sputum at visit 1 (1.8 ng·mL-1, 95% CI 1.2-2.7 ng·mL-1 versus 1.1 ng·mL-1, 95% CI 0.7-1.8 ng·mL-1) and visit 2 (1.5 ng·mL-1, 95% CI 1.0-2.5 ng·mL-1 versus 1.2 ng·mL-1, 95% CI 0.8-1.6 ng·mL-1; p=0.001). Repeating spontaneous and induced sputum procalcitonin levels 1 week later produced similar concentrations (p=0.29, intraclass correlation coefficient (ICC)=0.76 and p=0.72, ICC=0.70, respectively). Sputum procalcitonin is increased in patients with stable bronchiectasis and has potential as a biomarker of airway inflammation and infection in bronchiectasis.

ABO blood group and procoagulant factors: the hypercoagulation hypothesis ABO and Procoagulant Factors.

BACKGROUND: The correlation between procoagulant levels-factor VIII (FVIII), von Willebrand factor (vWF), and fibrinogen-and risk of thrombosis has been well documented in adult populations. We hypothesize that interaction of passively transferred isoagglutinins in premature neonates with a compromised immune system may trigger an immune response that can target the immature gastrointestinal tract. The objective of this study is to evaluate if there are procoagulant level differences in preterm newborns stratified by ABO blood group. METHODS: VWF, FVIII, and fibrinogen levels were analyzed in neonates ≤32 weeks and/or birthweight ≤1500 g over the first 6 weeks of life. Demographic, blood type, and transfusion data were collected. RESULTS: Elevations in vWF and FVIII were found to be statistically significant in the third week of life in non-O neonates vs. type O neonates. FVIII was also found to be significantly elevated in week 1. Transfused neonates also showed elevations between weeks 0 and 3. CONCLUSION: There appears to be a time-dependent variation in procoagulant factor levels in preterm newborns. Although the clinical significance remains unclear, prothrombotic factors vWF and FVIII are significantly higher in non-O blood-type preterm neonates in the third week of life.

Health care experiences of mothers of children with bronchiectasis in Counties Manukau, Auckland, New Zealand.

BACKGROUND: Bronchiectasis is a worsening public health problem in New Zealand. This study aimed to explore the health care experiences of mothers of children with bronchiectasis in the Counties Manukau District Health Board area of Auckland, New Zealand. METHODS: Semi-structured interviews were undertaken with ten mothers of children with bronchiectasis. Data were analysed using thematic analysis. RESULTS: Five themes emerged: 1) Searching for answers, describing mothers' search for a diagnosis; 2) (Dis)empowerment, describing mothers' acquisition of knowledge, leading to empowerment; 3) Health care and relationships, describing the impact of relationships on the mother's health care experiences; 4) A juggling act, describing the challenges of juggling health care with school, work and family; 5) Making it work, describing how mothers overcome barriers to access health care for their child. CONCLUSIONS: The health provider-parent relationship was crucial for fostering positive health care experiences. Mothers' acquisition of knowledge facilitated empowerment within those relationships. Additionally, mothers' perceptions of the quality and benefit of health services motivated them to overcome barriers to accessing care. Study findings may help to improve health care experiences for parents of children with bronchiectasis if identified issues are addressed.

Elevated Biomarkers of Inflammation and Coagulation in Patients with HIV Are Associated with Higher Framingham and VACS Risk Index Scores.

BACKGROUND: Biomarkers of inflammation and altered coagulation are of increasing interest as predictors of chronic disease and mortality in HIV patients, as well as the use of risk stratification scores such as the Framingham index and the Veterans Aging Cohort Study (VACS) score. METHODS: Demographic and laboratory data for 252 HIV patients were assessed for their relationship with 5 biomarkers: hsCRP, D-dimer, Cystatin C, IL-6 and TNF-alpha. Analysis of variance was used to model the association between the number of elevated biomarkers patients had and their Framingham 10 year cardiovascular risk and VACS scores. RESULTS: 87% of patients were male and 75.7% were virally suppressed (HIV RNA <48 copies/ml). The median and interquartile ranges for each biomarker were: hsCRP 1.65 ug/mL (0.73, 3.89), D-dimer 0.17 ug/mL (0.09, 0.31), Cystatin C 0.87 mg/L (0.78, 1.01), IL-6 2.13 pg/mL (1.3, 3.59), TNF-alpha 4.65 pg/mL (3.5, 5.97). 62.6% of patients had more than one biomarker >75th percentile, while 18.6% had three or more elevated biomarkers. Increased age, cigarette smoking, CD4 counts of <200 cells/mm3, Framingham scores and VACS scores were most strongly associated with elevations in biomarkers. When biomarkers were used to predict the Framingham and VACS scores, those with a higher number of elevated biomarkers had higher mean VACS scores, with a similar but less robust finding for Framingham scores. CONCLUSIONS: Despite viral suppression and immunological stability, biomarkers of inflammation and coagulation remain elevated in a significant number of patients with HIV and are associated with higher scores on risk stratification indices.

The prevalence of aortic calcification on vertebral fracture assessment imaging among patients with rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) are at increased risk of osteoporosis (OP) and cardiovascular disease (CVD). Dual-energy X-ray absorptiometry scans have been validated for identifying patients with RA at risk for fracture. Reliable CVD risk stratification remains an unmet need in this population. Vertebral fracture assessment (VFA)-detected abdominal aortic calcification (AAC) has been validated as a marker of CVD in other populations, but the prevalence among patients with RA is unknown. In this study, we determined the prevalence and severity of AAC on VFA scans in a cohort of patients with RA. AAC was detected in 211 of the 603 (35%) eligible subjects; 24% were graded as severe. In multivariable analyses, the presence of AAC was significantly associated with longer disease duration and higher disease activity (p<0.05). Further studies are needed on the relationship between AAC and CVD in patients with RA.

The prevalence of vertebral fracture on vertebral fracture assessment imaging in a large cohort of patients with rheumatoid arthritis.

OBJECTIVE: RA accelerates bone loss, increasing the risk of osteoporosis (OP) and fracture. DXA imaging has been validated for identifying RA patients at risk of fracture. The objective of this study was to assess the presence of asymptomatic vertebral fractures (VFs) in a cohort of patients with established RA referred for DXA using VF assessment (VFA) technology. METHODS: We determined the prevalence of VFs in a cohort of RA patients age ≥ 40 years fulfilling the 1987 ACR classification criteria. Two blinded radiologists independently reviewed all VFA scans to determine the presence and severity of VFs using Genant criteria. We compared the prevalence and severity of VFs between RA patients and determined the independent associations of different variables with VFs using multivariable logistic regression. RESULTS: Six hundred and three subjects fulfilled study inclusion criteria. Thirteen per cent of the entire cohort (77/603) had one or more vertebral deformities identified on VFA imaging: 58% were female with mean age 56 years. The prevalence of OP and osteopenia was 59% and 40%, respectively. The prevalence and severity of VFs showed significant correlation with spine T-scores (r = -0.37, P < 0.001) and femoral T-scores (r = -0.31, P < 0.001). In multivariable analyses VFs were significantly and independently associated with a longer duration of RA, markers of disease activity and severity. CONCLUSION: VFs were detected on VFA images in 13% of women and men with well-established RA referred for DXA testing. Longer duration and severity of RA disease were independent risk factors for fractures in our study.

Vertebral fracture assessment-detected abdominal aortic calcification and cardiovascular disease in rheumatoid arthritis.

OBJECTIVE: Individuals with rheumatoid arthritis (RA) are at increased risk for cardiovascular disease (CVD). Traditional prediction tools underestimate this risk. Vertebral fracture assessment (VFA)-detected aortic calcification enhances CVD risk stratification in the general population but its relationship in RA is unclear. We assessed the presence of abdominal aortic calcification (AAC) on VFA images, and its association with CVD in RA patients. METHODS: We determined the prevalence of cardiovascular events in a cohort of RA patients aged 40 years and older fulfilling the 1987 American College of Rheumatology classification criteria. Two blinded radiologists independently reviewed all VFA scans to determine the presence/severity of AAC using an established 24-point scale. Logistic regression analyses were performed to determine whether AAC could discriminate between RA patients with and without CVD, and to compare the ability of VFA-detected AAC to predict CVD to conventional CVD risk factors and the Framingham Risk Score. RESULTS: 603 subjects fulfilled study inclusion criteria. 230 (38%) subjects had 1 or more documented CVD event and 211 (35%) had AAC detected on VFA scans. Significantly more subjects with cardiovascular events had AAC on their VFA scans than controls (76% versus 10%; P < 0.05). VFA-detected AAC was a better predictor of CVD than traditional risk factors, and significantly out-performed the Framingham Risk Score for discriminating between the presence and absence of CVD (AUC 0.85 versus 0.58; P < 0.001). CONCLUSION: There was a significant association between VFA-detected AAC and CVD in our study population. This finding may enhance cardiovascular disease risk prediction in RA patients.