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After myocardial infarction (MI), the matrix response largely dictates how long you will live. Most heart failure after MI occurs a few months thereafter, aligning with the time fibroblasts require to deposit a scar. This dissertation focuses on how neonatal mammals can regenerate their hearts after MI and how we can interrogate these molecular hypotheses in-vitro. Chapter 1 provides an overview of the infarction cascade, known cellular and biomolecular contributions to inflammation, and the composition and structure of the extracellular matrix. Chapter 2 discusses how neonatal and adult cardiac healing differ. RNA-seq datasets were mined to provide insight to key pathways, receptors, and ligands that uniquely contribute to adult scar formation. Chapter 3 establishes an induced pluripotent stem cell (iPSC) to cardiac fibroblast (CF) differentiation through the epicardial lineage. Marker expression, matrix assembly, stress response, and chromatin architecture relative to other contemporary protocols and primary cells are characterized. Chapter 4 tests the central informatic hypotheses generated in chapter 2, particularly with respect to sterile inflammatory ligands (TGF-β, low molecular weight hyaluronic acid, and angiotensin II). It also investigates how these stress responses manifest in patients with single nucleotide polymorphisms (SNPs) in a long noncoding RNA (lncRNA) that worsen cardiovascular outcomes clinically. Chapter 5 is an extended discussion of the cumulative results, significance, and potential future approaches to cardiac fibrosis modeling. The discoveries herein demonstrate a novel method of reductionist fibrotic modeling in-vitro, highlight central fibrotic pathways, and suggest therapeutic targets.

With a well-established role in inflammation and immune function, vitamin D status has emerged as a potential factor for coronavirus disease-2019 (COVID-19).The purpose of this study was to evaluate the moderating effect of race on the relationship between vitamin D status and the risk of COVID-19 test positivity, and to compare propensity score (PS) model results to those obtained from classical bivariate and multivariable models, which have primarily comprised the literature to date.Electronic health record (EHR) data from TriNetX (unmatched n = 21,629; matched n = 16,602) were used to investigate the effect of vitamin D status, as measured by 25-hydroxyvitamin D [25(OH)D], on the odds of experiencing a positive COVID-19 test using multivariable logistic regression models with and without PS methodology.Having normal (Models which use weighting and matching methods resulted in smaller estimated effect sizes than models which do not use weighting or matching. These findings suggest a minimal protective effect of vitamin D status on COVID-19 test positivity in White individuals and no protective effect in Black individuals.

BACKGROUND AND AIMS: Conditions such as irritable bowel syndrome (IBS), functional dyspepsia, and functional constipation are among the prevalent gastrointestinal (GI) disorders classified as disorders of gut-brain interaction (DGBI), which can adversely affect the lives of sufferers. This study aimed to assess the degree and consequences of overlapping DGBI in a large population-based global scale. METHODS: Internet survey data from 54,127 adults (49.1% women) in 26 countries were analyzed by 4 GI anatomic regions (esophageal, gastroduodenal, bowel, and anorectal). The number of DGBI-affected GI regions was assessed, including associations with sex, age, disease severity, quality of life, psychosocial variables, and health care utilization. RESULTS: A total of 40.3% of surveyed individuals met Rome IV criteria for a DGBI. The percentages with 1-4 DGBI-affected GI regions were 68.3%, 22.3%, 7.1%, and 2.3%, respectively. The IBS symptom severity score increased significantly from 1 (207.6) to 4 (291.6) regions, as did non-GI symptom reporting (somatization), anxiety and depression, concerns and embarrassment about bowel function, doctor visits, medications, and abdominal surgeries (all P < .0001). Quality of life decreased with increasing number of DGBI regions (P < .0001). In a logistic mixed model, non-GI symptoms (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.08-1.10), being very vs not concerned (OR, 2.55; 95% CI, 2.27-2.90), being very vs not embarrassed about bowel function (OR, 1.20; 95% CI, 1.08-1.33), and mean number of doctor visits (OR, 1.23; 95% CI, 1.115-1.32) were most strongly associated with number of DGBI regions. CONCLUSIONS: DGBI in multiple anatomic GI regions is associated with increased psychological comorbidity, health care utilization, and IBS severity. Physician awareness of overlap could improve quality of care, prevent unnecessary interventions, and yield more positive health outcomes. ispartof: CLINICAL GASTROENTEROLOGY AND HEPATOLOGY vol:20 issue:5 pages:E945-E956 ispartof: location:United States status: published

OBJECTIVE The goal of this study was to assess the social determinants that influence access and outcomes for pediatric neurosurgical care for patients with Chiari malformation type I (CM-I) and syringomyelia (SM). METHODS The authors used retro- and prospective components of the Park-Reeves Syringomyelia Research Consortium database to identify pediatric patients with CM-I and SM who received surgical treatment and had at least 1 year of follow-up data. Race, ethnicity, and insurance status were used as comparators for preoperative, treatment, and postoperative characteristics and outcomes. RESULTS A total of 637 patients met inclusion criteria, and race or ethnicity data were available for 603 (94.7%) patients. A total of 463 (76.8%) were non-Hispanic White (NHW) and 140 (23.2%) were non-White. The non-White patients were older at diagnosis (p = 0.002) and were more likely to have an individualized education plan (p < 0.01). More non-White than NHW patients presented with cerebellar and cranial nerve deficits (i.e., gait ataxia [p = 0.028], nystagmus [p = 0.002], dysconjugate gaze [p = 0.03], hearing loss [p = 0.003], gait instability [p = 0.003], tremor [p = 0.021], or dysmetria [p < 0.001]). Non-White patients had higher rates of skull malformation (p = 0.004), platybasia (p = 0.002), and basilar invagination (p = 0.036). Non-White patients were more likely to be treated at low-volume centers than at high-volume centers (38.7% vs 15.2%; p < 0.01). Non-White patients were older at the time of surgery (p = 0.001) and had longer operative times (p < 0.001), higher estimated blood loss (p < 0.001), and a longer hospital stay (p = 0.04). There were no major group differences in terms of treatments performed or complications. The majority of subjects used private insurance (440, 71.5%), whereas 175 (28.5%) were using Medicaid or self-pay. Private insurance was used in 42.2% of non-White patients compared to 79.8% of NHW patients (p < 0.01). There were no major differences in presentation, treatment, or outcome between insurance groups. In multivariate modeling, non-White patients were more likely to present at an older age after controlling for sex and insurance status (p < 0.01). Non-White and male patients had a longer duration of symptoms before reaching diagnosis (p = 0.033 and 0.004, respectively). CONCLUSIONS Socioeconomic and demographic factors appear to influence the presentation and management of patients with CM-I and SM. Race is associated with age and timing of diagnosis as well as operating room time, estimated blood loss, and length of hospital stay. This exploration of socioeconomic and demographic barriers to care will be useful in understanding how to improve access to pediatric neurosurgical care for patients with CM-I and SM.

OBJECTIVE The primary objective of this trial was to determine if shunt entry site affects the risk of shunt failure. METHODS The authors performed a parallel-design randomized controlled trial with an equal allocation of patients who received shunt placement via the anterior entry site and patients who received shunt placement via the posterior entry site. All patients were children with symptoms or signs of hydrocephalus and ventriculomegaly. Patients were ineligible if they had a prior history of shunt insertion. Patients received a ventriculoperitoneal shunt after randomization; randomization was stratified by surgeon. The primary outcome was shunt failure. The planned minimum follow-up was 18 months. The trial was designed to achieve high power to detect a 10% or greater absolute difference in the shunt failure rate at 1 year. An independent, blinded adjudication committee determined eligibility and the primary outcome. The study was conducted by the Hydrocephalus Clinical Research Network. RESULTS The study randomized 467 pediatric patients at 14 tertiary care pediatric hospitals in North America from April 2015 to January 2019. The adjudication committee, blinded to intervention, excluded 7 patients in each group for not meeting the study inclusion criteria. For the primary analysis, there were 229 patients in the posterior group and 224 patients in the anterior group. The median patient age was 1.3 months, and the most common etiologies of hydrocephalus were postintraventricular hemorrhage secondary to prematurity (32.7%), myelomeningocele (16.8%), and aqueductal stenosis (10.8%). There was no significant difference in the time to shunt failure between the entry sites (log-rank test, stratified by age < 6 months and ≥ 6 months; p = 0.061). The hazard ratio (HR) of a posterior shunt relative to an anterior shunt was calculated using a univariable Cox regression model and was nonsignificant (HR 1.35, 95% CI, 0.98–1.85; p = 0.062). No significant difference was found between entry sites for the surgery duration, number of ventricular catheter passes, ventricular catheter location, and hospital length of stay. There were no significant differences between entry sites for intraoperative complications, postoperative CSF leaks, pseudomeningoceles, shunt infections, skull fractures, postoperative seizures, new-onset epilepsy, or intracranial hemorrhages. CONCLUSIONS This randomized controlled trial comparing the anterior and posterior shunt entry sites has demonstrated no significant difference in the time to shunt failure. Anterior and posterior entry site surgeries were found to have similar outcomes and similar complication rates.

Yoga therapy is an emerging integrative health approach that applies the practices and teachings of yoga for individuals with clinical concerns. It is generally offered as individual sessions between a yoga therapist and client or in a small group setting with several clients who share a clinical concern. Here we describe a third model for consideration- the yoga therapy dyad. A dyad includes two clients working simultaneously with a single yoga therapist and differs from both individual and small group sessions in the potential benefits and challenges. The yoga therapy dyad model that is detailed here was implemented as part of a feasibility trial along with group acupuncture therapy for chronic pain in an underserved population. Underserved populations are at risk for pain and reduced access to care. This pilot may inform future research, policy, education, and clinical practice.

Children with sickle cell disease (SCD) are at increased risk for severe illness due to severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). We describe the successful native lung recovery of a child with SCD referred for lung transplant (LTx) evaluation who was on prolonged veno-venous extracorporeal membrane oxygenation (VV-ECMO). He initially presented with acute chest syndrome complicated by SARS-CoV-2 infection that ultimately required dual-lumen, single bicaval VV-ECMO cannulation for respiratory support. Despite increased risk of hemolysis and thrombosis from SCD and SARS-CoV-2 infection, he was successfully supported on VV-ECMO for 71 days without complications leading to native lung recovery with meticulous management of his SCD therapy. This report provides new insight on our approach to VV-ECMO support in a child with SCD and SARS-CoV-2 infection. With a successful outcome, the patient has returned home but still on mechanical ventilation with LTx still an option if he is not eventually liberated from invasive respiratory support.

Objectives: To examine individual, medication, system, and healthcare related predictors of hospitalization and emergency department (ED) presentation within 90 days of entering the aged care sector, and to create risk-profiles associated with these outcomes. Design and setting: Retrospective population-based cohort study using data from the Registry of Senior Australians. Participants: Older people (aged 65 and older) with an aged care eligibility assessment in South Australia between January 1, 2013 and May 31, 2016 (N = 22,130). Measurements: Primary outcomes were unplanned hospitalization and ED presentation within 90 days of assessment. Individual, medication, system, and healthcare related predictors of the outcomes at the time of assessment, within 90 days or 1-year prior. Fine–Gray models were used to calculate subdistribution hazard ratios (sHR) and 95% confidence intervals (CI). Harrell's C-index assessed predictive ability. Results: Four thousand nine-hundred and six (22.2%) individuals were hospitalized and 5028 (22.7%) had an ED presentation within 90 days. Predictors of hospitalization included: being a man (hospitalization sHR = 1.33, 95% CI 1.26–1.42), ≥3 urgent after-hours attendances (hospitalization sHR = 1.21, 95% CI 1.06–1.39), increasing frailty index score (hospitalization sHR = 1.19, 95% CI 1.11–1.28), individuals using glucocorticoids (hospitalization sHR = 1.11, 95% CI 1.02–1.20), sulfonamides (hospitalization sHR = 1.18, 95% CI 1.10–1.27), trimethoprim antibiotics (hospitalization sHR = 1.15, 95% CI 1.03–1.29), unplanned hospitalizations 30 days prior (hospitalization sHR = 1.13, 95% CI 1.04–1.23), and ED presentations 1 year prior (hospitalization sHR = 1.07, 95% CI 1.04–1.10). Similar predictors and hazard estimates were also observed for ED presentations. The hospitalization models out-of-sample predictive ability (C-index = 0.653, 95% CI 0.635–0.670) and ED presentations (C-index = 0.647, 95% CI 0.630–0.663) were moderate. Conclusions: One in five individuals with aged care eligibility assessments had unplanned hospitalizations and/or ED presentation within 90 days with several predictors identified at the time of aged care eligibility assessment. This is an actionable period for targeting at-risk individuals to reduce hospitalizations. Refereed/Peer-reviewed

Rapid diagnosis of preeclampsia is necessary to ensure timely administration of appropriate care and prevent the potentially catastrophic complications of the condition affecting both mothers and babies. While the diagnostic superiority of angiogenic blood biomarkers such as placental growth factor has recently been demonstrated, there is an urgent need to develop point-of-care (PoC) technologies that allow rapid, quantitative, and accurate testing for these markers within local communities. Towards addressing this need, here we report on a fully integrated biodiagnostic platform based on nanoscale indium oxide field effect transistor (FET) sensors. The high-performance FET sensors are integrated with blood sample processing cartridges that minimize the need for operator intervention during the assay and eliminate the need for analytical equipment. Within 40 minutes and from 30 µL of blood, the FET platform could reliably measure PlGF with a limit of detection of 0.06 pg/mL and a five order of magnitudes dynamic range. Pilot clinical validation in four preeclamptic pregnancies confirmed that the accuracy and reliability of the FET platform, paving the way for further development to a much-needed point-of-care preeclampsia testing. Refereed/Peer-reviewed

Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

Summary Objective To evaluate if returning to pivoting sport following anterior cruciate ligament reconstruction (ACLR) is associated with longitudinal structural and symptomatic osteoarthritis outcomes. Design Eighty-one adults aged 18–50 years were followed prospectively 1- to 5-years post-ACLR. Return to pivoting sport was assessed at 1-, 3- and 5-years. Longitudinal changes in osteoarthritis features were evaluated from 1- and 5-year magnetic resonance imaging (MRI)s using MRI Osteoarthritis Knee Score (MOAKS). Radiographic osteoarthritis and self-reported knee symptoms, function and quality of life were assessed using the Osteoarthritis Research Society International (OARSI) atlas and Knee injury Osteoarthritis Outcome Score (KOOS), respectively, at 5 years post-ACLR. Generalised linear models (adjusted for baseline characteristics) assessed whether returning to pivoting sport was associated with risk of worsening osteoarthritis features on MRI, radiographic osteoarthritis and KOOS. Results Thirty participants returned to pivoting sport 1-year post-ACLR and 50 returned at any time (i.e., 1-, 3- or 5-years). Returning to pivoting sport was not associated with worsening of any MRI osteoarthritis feature (risk ratio (RR) range: 0.59–2.91) or 5-year KOOS (β range: −2.73–3.69). Returning to pivoting sport at 1-year and up to 5-years post-ACLR was associated with a 50% (RR 0.49, 95%CI 0.10–2.37) and 40% (RR 0.60, 95%CI 0.16–2.17) reduced risk of radiographic osteoarthritis, respectively, but these risk reductions were inconclusive due to wide confidence intervals. Conclusion After ACLR, returning to pivoting sport was not associated with increased risk of worsening knee osteoarthritis features on MRI, radiographic osteoarthritis or knee symptoms. Participation in pivoting sport need not be avoided as part of osteoarthritis secondary prevention strategies.

Background In response to the COVID-19 pandemic, family presence restrictions in neonatal intensive care units (NICU) were enacted to limit disease transmission. This has resulted in communication challenges, negatively impacting family integrated care. Aim To develop clinical care pathways to ensure optimal neonatal care to support families in response to parental presence restrictions imposed during the COVID-19 pandemic. Methods An agile, co-design process utilizing expert consensus of a large interdisciplinary team and focus groups and semi-structured interviews with families and HCPs were used to co-design clinical virtual care pathways. Results Three clinical virtual care pathways were co-designed: (1) building and maintaining relationships between family and healthcare providers; (2) awareness of resources; and (3) standardized COVID-19 messaging. Modifications were made to optimize uptake and utilization in the clinical areas. Conclusion Clinical care virtual pathways were successfully co-designed to meet these needs to ensure more equitable family centered care.

Background Nurses are key to the success of patient engagement, yet we know little about nurses’ perceptions on treatment engagement and how they can contribute to treatment engagement. Qualitative evidence to identify factors that influence treatment engagement among patients with CVD from nurse’s perspective is limited. Methods This systematic review of qualitative research was based on the PRISMA reporting guidelines. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist was used to assess quality by two reviewers independently. Data were collected from Medline, Web of Science, CINAHL, PsychINFO, Embase- Non-Medline, Scopus, and the Cochrane Library, were systematically searched from 2001 to 2020. The search strategy included keywords and MeSH terms to identify relevant studies written in English. Results Eight articles were included in the review. Four key themes were synthesised from the findings: nurses need training and up to date information, providing support for patients, patient motivation to engage with treatment plans and perceived lack of time. Conclusion Nurses described the importance of training to help them support patients to engage as effectively as possible and their role in providing social and psychological support. They also described the importance of patient motivation to engage in a treatment and plan and sustain engagement and time.

AIM To synthesise quantitative evidence on factors that impact hospital readmission rates following ACS with comorbidities. DESIGN Systematic review and narrative synthesis. DATA SOURCES A search of eight electronic databases, including Embase, Medline, PsycINFO, Web of Science, CINAHL, Cochrane Library, Scopus and the Joanna Briggs Institute (JBI). REVIEW METHODS The search strategy included keywords and MeSH terms to identify English language studies published between 2001 and 2020. The quality of included studies was assessed by two independent reviewers, using Joanna Briggs Institute (JBI) critical appraisal tools. RESULTS Twenty-four articles were included in the review. All cause 30-day readmission rate was most frequently reported and ranged from 4.2% to 81%. Reported factors that were associated with readmission varied across studies from socio-demographic, behavioural factors, comorbidity factors and cardiac factors. Findings from some of the studies were limited by data source, study designs and small sample size. CONCLUSION Strategies that integrate comprehensive discharge planning and individualised care planning to enhance behavioural support are related to a reduction in readmission rates. It is recommended that nurses are supported to influence discharge planning and lead the development of nurse-led interventions to ensure discharge planning is both coordinated and person-centred.

Purpose The purpose of this study is to investigate the experiences of staff during the development and implementation of an Australian-first, family-focussed service addressing the mental health needs of young people (aged 12–25 years) with an intellectual disability. This study aims to understand the challenges and successes of the staff team when navigating their way in a new program working with a complex client group. Design/methodology/approach This study used a thematic analysis on data collected from focus groups at two time points in the implementation phase of the new program. Thematic analysis of the data was conducted to identify important themes relating to the staff’s challenges, successes and learning. Findings The findings showed that there was a lot of adaptation needed for staff members trained in either mental health, or disability, but not both. Another key finding was the importance of working with the young person’s family system as well as their existing system of support services. This major focus of the work for staff could be challenging due issues arising in the family unit and a lack of collaboration between services. Working with this complex client group was viewed as challenging and stress inducing; however, the motivation and attitudes of staff were found to be positive factors in the running of the program. Originality/value This paper makes an original contribution to the field, as it provides a unique look at staff experiences when needing to adapt to a new and challenging workplace that was the first-of-its-kind in Australia.

Magnetic resonance spectroscopy (MRS) is a valuable adjunct to structural brain imaging. State-of-the-art MRS has benefited greatly from recent technical advancements. Neurometabolic alterations in pediatric brain diseases have implications for diagnosis, prognosis, and therapy. Herein, the authors discuss MRS technical considerations and applications in the setting of various pediatric disease processes including tumors, metabolic diseases, hypoxic/ischemic encephalopathy/stroke, epilepsy, demyelinating disease, and infection.

AIM This review assessed the effectiveness of interventions using a goal-setting approach on glycaemic control for people diagnosed with prediabetes or type 2 diabetes. DESIGN A systematic review guided by the Joanna Briggs Institute methodology for conducting systematic reviews of primary research studies was conducted. DATA SOURCES Randomized controlled trials and experimental studies with a minimum follow-up period of 6 months were considered for inclusion. The primary outcome was change in glycaemic control as measured by glycated haemoglobin (%) and/or fasting plasma glucose (mg/dl). A systematic search of seven electronic databases was completed in October 2020. REVIEW METHODS Papers meeting the inclusion criteria were critically appraised using the Joanna Briggs Institute tools for critical appraisal followed by data extraction. A Grading of Recommendations Assessment, Development and Evaluation assessment was conducted to assess the overall certainty of the evidence. Fixed-effect meta-analyses were completed to demonstrate the mean effect for each outcome of interest. RESULTS Twenty one studies were included in this review. Goal setting was more effective than usual care for glycaemic control in prediabetes at 6 months and at 12 months for fasting plasma glucose (mg/dl) and glycated haemoglobin (%). Goal setting was more effective than usual care for glycaemic control in type 2 diabetes for fasting plasma glucose (mg/dl) at 6 months, fasting plasma glucose (mg/dl) at 12 months, glycated haemoglobin (%) at 6 months and glycated haemoglobin (%) at 12 months. CONCLUSION The evidence suggests goal setting is effective in supporting people to achieve glycaemic targets in prediabetes and type 2 diabetes.

Objective Current competencies required for fellowship of the RANZCP require psychiatry registrars to have experience in working with clients across all age groups, as well as working with families and the client’s wider network, however gaining this experience is not always easy for trainees. This paper reports on the experience of participating in Single Session Family Therapy (SSFT) during registrar training as a different modality for learning. Method: An online survey was conducted with fourteen registrars who had participated in SSFT during their child and adolescent rotation. Qualitative and simple quantitative data were collected and analysed. Results: Participating in SSFT during training was initially daunting, but had a positive effect on trainees, including influencing some towards focussing their future sub-specialisation in the child and youth area. Experience came through learning by doing, and seeing change. Registrars learnt about: understanding the role of the family; teamwork; technical skills; and gained confidence. Conclusions: Opportunities for trainees to participate in SSFT enables powerful learning beyond what can be taught in the classroom. Such opportunities may enhance registrars’ perceptions of family work, and may positively influence decision about future sub-specialisation.

White matter pathologies are critically involved in the etiology of vascular cognitive impairment-dementia (VCID), Alzheimer's disease (AD), and Alzheimer's disease and related diseases (ADRD), and therefore need to be considered a treatable target ( Roseborough A, Hachinski V, Whitehead S. White matter degeneration - a treatable target? Roseborough et al. JAMA Neurol [Internet]. 2020 Apr 27;77(7):793-4, [1] . To help address this often-missed area of research, several workshops have been sponsored by the Leo and Anne Albert Charitable Trust since 2015, resulting in the incorporation of "The Albert Research Institute for White Matter and Cognition" in 2020. The first annual "Institute" meeting was held virtually on March 3-4, 2021. The Institute provides a forum and workspace for communication and support of the advancement of white matter science and research to better understand the evolution and prevention of dementia. It serves as a platform for young investigator development, to introduce new data and debate biology mechanisms and new ideas, and to encourage and support new research collaborations and directions to clarify how white matter changes, with other genetic and health risk factors, contribute to cognitive impairment. Similar to previous Albert Trust-sponsored workshops (Barone et al. in J Transl Med 14:1-14, [2]; Sorond et al. in GeroScience 42:81-96, [3]), established expert investigators were identified and invited to present. Opportunities to attend and present were also extended by invitation to talented research fellows and younger scientists. Also, updates on institute-funded research collaborations were provided and discussed. The summary that follows is a synopsis of topics and discussion covered in the workshop.

Background Irritable bowel syndrome (IBS) is highly prevalent worldwide but mechanisms for healthcare seeking behaviours in this patient group are poorly understood. Objective To describe healthcare utilization and identify factors associated with seeking healthcare amongst IBS subjects in the general population. Methods An internet survey was completed by 6,300 individuals equally distributed between United States, United Kingdom and Canada. The Rome IV diagnostic questionnaire was used to identify subjects with IBS. Data on demographics, medical history, gastrointestinal (GI) and non‐GI symptoms, quality of life and health care consumption was collected. Results A total of 5,931 subjects were included; 274 (4.6%) IBS subjects and 5657 (95.3%) non‐IBS controls. IBS subjects reported more doctor consultations for both GI and other health problems as well as increased use of medication and rate of abdominal surgery (appendectomy excluded). Having healthcare insurance or access to free public healthcare (adjusted odds ratio (AOR) 4.49, 95% confidence interval (CI) 1.31–15.44), followed by high frequency of bloating (AOR 2.65, 95% CI 1.42–4.93) and increasing age (AOR 1.02, 95% CI 1.01–1.05) were found to be independently associated with being an IBS consulter while doctor‐diagnosed IBS subjects were more likely to be female and to report abdominal pain as their most bothersome GI symptom than other consulters with IBS. Conclusion IBS subjects have higher healthcare utilization than non‐IBS controls, medication use and abdominal surgery included. Furthermore, consulters with and without an IBS diagnosis differ in sex distribution and symptom profiles. Hence, awareness of the possibility of unnecessary medical and surgical treatment in IBS subjects and a sex‐related diagnostic bias by doctors is warranted.

Objective Pulse oximetry is commonly used in Neonatology, however recent adult data suggest racial disparity in accuracy, with overestimation of oxygen saturation for Black patients. Study design Black and White infants 90% when SaO2

COVID‐19 has resulted in unprecedented changes to maternity care across Australia. This study aims to analyse trends in maternity consultations and the uptake of telehealth in Victoria and New South Wales (NSW) since the first restrictions to reduce COVID‐19 transmission were implemented. From March 2020 to April 2021, a higher proportion of antenatal care consultations was delivered via telehealth in Victoria compared to NSW (13.8% vs 7.4%, P

In this retrospective cohort study, we characterize the health profile of preterm males with Duchenne muscular dystrophy. Major clinical milestones (ambulation cessation, assisted ventilation use, and onset of left ventricular dysfunction) and corticosteroids use in males with Duchenne muscular dystrophy identified through a population-based surveillance system were analyzed using Kaplan-Meier survival curves and Cox proportional hazards modeling. The adjusted risk of receiving any respiratory intervention among preterm males with Duchenne muscular dystrophy was 87% higher than among the corresponding full-term males with Duchenne muscular dystrophy. The adjusted risks for ambulation cessation and left ventricular dysfunction were modestly elevated among preterm compared to full-term males, but the 95% confidence intervals contained the null. No difference in the start of corticosteroid use between preterm and full-term Duchenne muscular dystrophy males was observed. Overall, the disease course seems to be similar between preterm and full-term males with Duchenne muscular dystrophy; however, pulmonary function seems to be affected earlier among preterm males with Duchenne muscular dystrophy.

Background Nurses are essential in global strategies to improve population health. However, there is a paucity of research that describes the application of primary health care from a nursing perspective. Australian remote area nurses work in primary health care clinics which are often the only health care service within the community. Services include acute care response as well as health promotion and public health activities. Question, Hypothesis or Aim To explore the meaning and application of primary health care principles from the perspective of nurses in Australian remote settings. Methods Telephone interviews were conducted with registered nurses and nurse practitioners working in Australian remote settings using constructivist grounded theory methods during 2014 and 2015. Findings Nurses in remote settings considered primary health care to be an holistic social model of care that included caring for the community as well as the individual. However, they were unable to provide care consistent with their intention due to the resource-poor nature of the remote setting. Inadequate physical resources, limited specialist health services, and a lack of time were found to impact on remote area nurses’ abilities to provide primary health care. Discussion This study is unique in its description of a cause of remote area nurse stress as being the inability to provide primary health care in line with their expectations. Conclusion Appropriate resourcing is essential for nurses to be able to provide a comprehensive array of holistic services in line with community-identified need that also reflect their own definitions of primary health care.

Background Understanding the prognostic impact of right ventricular dysfunction (RVD) in cardiogenic shock (CS) is a key step toward rational diagnostic and treatment algorithms and improved outcomes. Using a large multicenter registry, we assessed (1) the association between hemodynamic markers of RVD and in-hospital mortality, (2) the predictive value of invasive hemodynamic assessment incorporating RV evaluation, and (3) the impact of RVD severity on survival in CS. Methods and Results Inpatients with CS owing to acute myocardial infarction (AMI) or heart failure (HF) between 2016 and 2019 were included. RV parameters (right atrial pressure, right atrial/pulmonary capillary wedge pressure [RA/PCWP], pulmonary artery pulsatility index [PAPI], and right ventricular stroke work index [RVSWI]) were assessed between survivors and nonsurvivors, and between etiology and SCAI stage subcohorts. Multivariable logistic regression analysis determined hemodynamic predictors of in-hospital mortality; the resulting models were compared with SCAI staging alone. Nonsurvivors had a significantly higher right atrial pressure and RA/PCWP and lower PAPI and RVSWI than survivors, consistent with more severe RVD. Compared with AMI, patients with HF had a significantly lower RA/PCWP (0.58 vs 0.66, P = .001) and a higher PAPI (2.71 vs 1.78, P Conclusions RVD is associated with poor outcomes in CS, with key differences across etiology and shock severity. Further studies are needed to assess the usefulness of RVD assessment in guiding therapy.

Purpose Sympathetic activation results in a functional distribution of venous blood from the unstressed reservoir to the hemodynamically active stressed compartment. Such redistribution has been hypothesized to contribute importantly to the elevated filling pressures observed in decompensated heart failure and cardiogenic shock (CS). We recently reported a novel computational method to estimate SBV by fitting measured hemodynamic data from patients to outputs from a cardiovascular model. We hypothesized that estimated stressed blood volume (eSBV) may correlate with severity and clinical outcomes in cardiogenic shock. Methods Hemodynamic parameters including eSBV were compared among a subset of patients from the Cardiogenic Shock Working Group (CSWG) registry who had a complete set of hemodynamic data. eSBV was compared across shock etiologies (AMI vs HF-CS), SCAI stage, and between survivors and non-survivors. Results Among 528 CSWG registry patients analyzed, 25.4% had AMI-CS and 61.9% had HF-CS. Mean eSBV was 2423 ± 531 mL/70 kg (normal value ∼1500 mL) and was similar between the AMI-CS and HF-CS subgroups (2421 ± 478 vs 2342 ± 599 mL/70kg, p=0.90). eSBV increased with increasing SCAI stage (B, 2029 ± 540; C, 2305 ± 505; D, 2496 ± 507; E, 2707 ± 420 mL/70 kg, p Conclusion eSBV is a novel integrated index of congestion which correlates with shock severity. eSBV was higher in patients with HF-CS who died while no difference was observed in AMI-CS, suggesting that congestion may play a more significant role in the deterioration of patients with HF-CS.

In an Australian nursing home population, associations between cognitive function and 12-month hospitalizations and costs were examined. Participants with dementia had 57% fewer hospitalizations compared to those without dementia, with 41% lower mean hospitalization costs; poorer cognition scores were also associated with fewer hospitalizations. The cost per admission for those with dementia was 33% greater due to longer hospital stays (5.5 days versus 3.1 days for no dementia, p = .05). People with dementia were most frequently hospitalized for fractures. These findings have policy implications for increasing investment in accurate and timely diagnosis of dementia and fall and fracture prevention strategies to further reduce associated hospitalization costs Refereed/Peer-reviewed

Background Understanding current patterns of antibiotic use in residential aged care facilities (RACFs) is essential to inform stewardship activities, but limited utilization data exist. This study examined changes in prevalence and consumption of antibiotics in Australian RACFs between 2005–2006 and 2015–2016. Methods This population-based, repeated cross-sectional analysis included all long-term permanent residents of Australian RACFs between July 2005 and June 2016 who were aged ≥ 65 years. The yearly prevalence rate of antibiotic use and number of defined daily doses (DDDs) of systemic antibiotics per 1000 resident-days were determined annually from linked pharmaceutical claims data. Trends were assessed using ordinary least squares regression. Results This study included 502 752 residents from 3218 RACFs, with 424.9 million resident-days analyzed. Antibiotics were dispensed on 5 608 126 occasions during the study period, of which 88% were for oral use. Cefalexin, amoxicillin-clavulanic acid, and trimethoprim were the most commonly dispensed antibiotics. The annual prevalence of antibiotic use increased from 63.8% (95% confidence interval [CI], 63.3%–64.4%) to 70.3% (95% CI, 69.9%–70.7%) between 2005–2006 and 2015–2016 (0.8% average annual increase, P Conclusions This nationwide study showed substantial increases in both prevalence of use and total consumption of antibiotics in Australian RACFs between 2005 and 2016. The increasingly widespread use of antibiotics in Australian RACFs is concerning and points to a need for enhanced efforts to optimize antibiotic use in this setting.

Background There is a high burden of antipsychotic use in residential aged care facilities (RACFs) and there is concern regarding potential inappropriate prescribing of antipsychotics in response to mild behavioural symptoms. Antipsychotic use has been associated with a higher risk of mortality in community-dwelling older adults with dementia, but few studies have examined associations upon RACF entry. Aims To examine associations between incident antipsychotic use and risk of mortality for people with and without diagnosed dementia in RACFs. Methods A retrospective cohort study, employing a new-user design (individuals did not receive an antipsychotic 6 months before enrolment) of 265,820 people who accessed RACFs in Australia between 1/4/2008 and 30/6/2015 was conducted. Cox regression models were used to examine adjusted associations between antipsychotic use in the first 100 days of RACF entry and mortality. Results In the 100 days after entering care, 29,455 residents (11.1%) were dispensed an antipsychotic. 180,956 (68.1%) residents died [38,249 (14.4%) were related to cerebrovascular causes] over a median 2.1 years (interquartile range 1.0–3.6) follow-up. Of the residents included, 119,665 (45.0%) had a diagnosis of dementia. Incident antipsychotic use was associated with higher risk of mortality in residents with dementia (adjusted hazard ratio 1.20, 95% confidence interval 1.18–1.22) and without dementia (1.28, 1.24–1.31). Conclusion Initiation of antipsychotics after moving to RACFs is associated with a higher risk of mortality. Careful consideration of the potential benefits and harms should be given when starting a new prescription for antipsychotics for people moving to RACFs.

Objective: To examine the prevalence of psychotropic medicine dispensing before and after older people enter residential care. Design: Retrospective national cohort study; analysis of Registry of Senior Australians (ROSA) data. Setting, participants: All concession card-holding residents of government-subsidised residential aged care facilities in Australia who entered residential care for at least three months between 1 April 2008 and 30 June 2015. Main outcome measures: Proportions of residents dispensed antipsychotic, benzodiazepine, or antidepressant medicines during the year preceding and the year after commencing residential care,by quarter. Results: Of 322 120 included aged care residents, 68 483 received at least one antipsychotic (21.3%; 95% CI, 21.1–21.4%), 98 315at least one benzodiazepine (30.5%; 95% CI, 30.4–30.7%), and 122 224 residents at least one antidepressant (37.9%; 95% CI,37.8–38.1%) during their first three months of residential care;31 326 of those dispensed antipsychotics (45.7%), 38 529 of those dispensed benzodiazepines (39.2%), and 25 259 residents dispensed antidepressants (19.8%) had not received them in the year preceding their entry into care. During the first three months of residential care, the prevalence of antipsychotic (prevalence ratio[PR], 3.37; 95% CI, 3.31–3.43) and antidepressant dispensing (PR,1.05; 95% CI, 1.04–1.07) were each higher for residents with than for those without dementia; benzodiazepine dispensing was similar for both groups (PR, 1.01; 95% CI, 0.99–1.02). Conclusions: Dispensing of psychotropic medicines to older Australians is high before they enter residential care but increases markedly soon after entry into care. Non-pharmacological behavioural management strategies are important for limiting the prescribing of psychotropic medicines for older people in the community or in residential care. Refereed/Peer-reviewed

Background & Aims The diagnostic criteria for fecal incontinence (FI) were made more restrictive in the Rome IV revision. We aimed to determine the characteristics of FI patients defined by the Rome IV criteria, assess how FI frequency and amount affect quality of life, identify risk factors, and compare prevalence values among countries. Methods We performed an internet-based survey of 5931 subjects in the United States, Canada, and the United Kingdom, from September to December 2015. Subjects were stratified by country, sex, and age. Responders answered questions about diagnosis, health care use, and risk factors. We performed multivariate linear regression analysis to identify risk factors for FI. Results FI was reported by 957 subjects (16.1%) but only 196 (3.3%) fulfilled the Rome IV criteria. Frequency of FI was less than twice a month for 672/957 subjects (70.2%) and duration was less than 6 months for 285/957 subjects (29.8%). Quality of life was significantly impaired in all subjects with FI compared to subjects with fecal continence. The strongest risk factors for FI were diarrhea, urgency to defecate, and abdominal pain. FI was more prevalent in the United States than in the United Kingdom. Between-country differences were due to less diarrhea and urgency in the United Kingdom. Conclusions Rome IV FI prevalence is lower than previous estimates because the new criteria exclude many individuals with less frequent or short duration FI. These excluded patients have impaired quality of life. It might be appropriate to make a diagnosis of FI for all patients with FI ≥2 times in 3 months and to provide additional information on frequency, duration, and amount of stool lost to assist clinicians in treatment selection.