Search

Summary: The development of new treatments for heart failure lack animal models that encompass the increasingly heterogeneous disease profile of this patient population. This report provides evidence supporting the hypothesis that Western Diet−fed, aortic-banded Ossabaw swine display an integrated physiological, morphological, and genetic phenotype evocative of cardio-metabolic heart failure. This new preclinical animal model displays a distinctive constellation of findings that are conceivably useful to extending the understanding of how pre-existing cardio-metabolic syndrome can contribute to developing HF. Key Words: cardio-metabolic disease, heart failure, integrative pathophysiology, preclinical model of cardiovascular disease

Extravasation of iodinated contrast material (ICM) is an uncommon complication (0.1%-1.2%) following intravenous injection for computed tomography exams and other procedures. Most cases of contrast extravasation are mild and resolve without treatment. Alternative injections sites are occasionally necessary among patients with difficult vascular access and are at increased risk of contrast extravasation and subsequent complications compared to the antecubital fossa. We describe a rare case of airway compromise necessitating intubation following iodinated contrast extravasation from an external jugular IV line. Additional care and monitoring must be performed during and after injection of contrast into these higher-risk vascular access sites.

Pneumocephalus is a condition defined by air present in the intracranial space. There are several causes of pneumocephalus, however this is a case of a patient who developed pneumocephalus following a cervical epidural steroid injection. Uniquely, this patient's chief complaint was sudden onset of syncope, and respiratory arrest following the injection. The diagnosis was made by CT, and conservative treatment was used for resolution of the condition. Patients with pneumocephalus can present with a wide range of neurologic symptoms, and prompt recognition and treatment are key to preventing irreversible neurologic damage.

Objective: To calculate the prevalence of renal cell carcinoma (RCC), upper urinary tract urothelial carcinoma (UT-UC), and lower urinary tract urothelial carcinoma (LT-UC) in patients with gross asymptomatic microhematuria (AMH) and symptomatic microhematuria (SMH). Patients and Methods: This study was a population-based retrospective descriptive study. The study was approved by both the Mayo Clinic Institutional Review Board and the Olmsted Medical Center Institutional Review Board, and the population used was Olmsted County residents. A total of 4453 patients who presented with an initial episode of hematuria from January 1, 2000, through December 30, 2010, were included. Of the 4453 patients (median age, 58 years; interquartile range, 44.6-73.3 years), 1487 (33.4%) had gross hematuria, 2305 (51.8%) had AMH, and 661 (14.8%) had SMH. Results: In the 1487 patients with gross hematuria, the prevalence of RCC, UT-UC, and LT-UC was 1.3%, 0.8%, and 9.0%, respectively. In the 2305 patients with AMH, the prevalence of RCC, UT-UC, and LT-UC was 0.2%, 0.3%, and 1.6%, respectively. In the 661 patients with SMH, the prevalence of RCC, UT-UC, and LT-UC was 0.6%, 0.2%, and 0.3%, respectively. Age was the most relevant risk factor for any hematuria type. Conclusion: This unique cohort study reported that the prevalence of RCC or UC in patients with AMH and SMH was low, especially in the young cohort, and a large number of intense work-ups, such as cystoscopy and computed tomography urography, currently conducted could be omitted if stratified by hematuria type and age.

Atopic eczema is a common and complex disease. Missing genetic hereditability and increasing prevalence in industrializing nations point toward an environmental driver. We investigated the temporal association of weather and pollution parameters with eczema severity. This cross-sectional clinical study was performed between May 2018 and March 2020 and is part of the Tower Hamlets Eczema Assessment. All participants had a diagnosis of eczema, lived in East London, were of Bangladeshi ethnicity, and were aged 10 after previous ambient exposure to commonly studied meteorological variables and pollutants. There were 430 participants in the groups with Eczema Area and Severity Index ≤ 10 and 149 in those with Eczema Area and Severity Index > 10. Using logistic generalized additive models and a model selection process, we found that tropospheric ozone averaged over the preceding 270 days was strongly associated with eczema severity alongside the exposure to fine particles with diameters of 2.5 μm or less (fine particulate matter) averaged over the preceding 120 days. In our models and analyses, fine particulate matter appeared to largely act in a supporting role to ozone. We show that long-term exposure to ground-level ozone at high levels has the strongest association with eczema severity.

Cisplatin causes apoptosis of dorsal root ganglia (DRG) neurons. The amount of platinum binding to DNA correlates with cisplatin toxicity in cancer cells11 Genomic DNA platinum content of cultured embryonic DRG neurons and PC12 cells was assayed using inductively coupled plasma mass spectrometry (ICP-MS). Throughout these studies, “cisplatin” refers to the specific drug; “platinum” to the bound form of the drug that is measured in ICP-MS.. Cisplatin binds neuronal DNA more than a neuron-like dividing cell line (PC12); 10-fold at 24 h and 24-fold greater at 72 h. Difference in platinum accumulation was not due to dividing versus post-mitotic state, or to a difference in rate of repair. There was overall greater accumulation of platinum in DRG neurons. In vivo DNA–Platinum binding in adult (300 g) rat DRG was greater than in multiple other tissues. Concomitant treatment with high-dose NGF prevented cisplatin-mediated neuronal apoptosis in vitro but did not reduce adduct formation. Our results show that NGF does not alter platination of DNA, indicating that it interrupts the platinum death pathway after adduct formation. In addition, disproportionate platinum accumulation may explain why a drug aimed at killing rapidly dividing cells causes sensory neurotoxicity.

Cisplatin causes apoptosis of DRG neurons in vitro and in vivo that can be prevented by high dose NGF. Design of a neuronal rescue strategy for patients receiving cisplatin will be facilitated by knowledge of the mechanism by which cisplatin causes DRG death. Inhibition of the fas receptor/ligand interaction prevents apoptosis in certain cancer cell lines treated with DNA damaging agents, including cisplatin. We demonstrated that killing curves from mice lacking a functional fas receptor and wild-type controls were not different over a wide range of therapeutically relevant concentrations. However, cisplatin treatment of DRG caused redistribution of cytosolic bax and mitochondrial release of cytochrome c. Bax redistribution was prevented by high dose NGF. This demonstrates for the first time that cisplatin does not signal for death via the fas pathway, but it does initiate the mitochondrial stress pathway in neurons and that NGF blocks death upstream of bax redistribution.

Cisplatin is used in the treatment of ovarian and testicular cancer. Twenty percent of patients cannot be optimally treated because of sensory neurotoxicity. Human and animal studies demonstrate that the dorsal root ganglion neuron is the primary target of drug injury. We have previously demonstrated that cisplatin causes neuronal apoptosis in vitro. We now report a reproducible animal model of cell death induced by cisplatin. Drug was administered for 1 or 2 cycles of 5 days separated by 5 days. Total dose administered was 0, 5, 7.5, 10, or 15 mg/kg. Ganglia from 34 animals were processed and examined using in situ hybridization for cyclin D1 messenger RNA and digoxigenin coupled TUNEL staining. Overall, 2.9 ± 3.9% of neurons were TUNEL positive in treated rats compared with 0.2 ± 0.3% in controls (P < .005). There was a strong positive correlation (r2 = 0.88; P = 0.018) between percentage of TUNEL stained DRG and cumulative dose of cisplatin. Two independent approaches to quantitation of in situ cyclin D1 hybridization were used; blinded grading by an observer and measurement of color density using digital image analysis. Both demonstrated dramatic upregulation of expression of cyclin D1 mRNA in treated compared with control rats. This demonstrates that apoptosis of neurons is preceded by aberrant reentry into G1 phase of the cell cycle in an animal model.

Objectives: Vaccine administration where pregnant individuals receive prenatal care may increase vaccine coverage. Availability of influenza vaccine at prenatal care visits is not standard in Canada. Since the 2016-2017 influenza season, pregnant individuals can receive the influenza vaccine at point of care (POC) in an urban clinic in Calgary, Alberta. The objective of this study was to descriptively examine vaccination rates across multiple influenza seasons for a POC-vaccination in pregnancy (VIP) intervention and describe associations between influenza vaccine coverage and comorbidities and area-level socioeconomic status., Methods: A before-and-after study design was used to examine vaccine coverage across six consecutive influenza seasons: two before (2014-2015 and 2015-2016) and four after POC-VIP implementation (2016-2017 to 2019-2020). We identified the birth cohort and measured influenza vaccine uptake using clinical and administrative databases. Influenza vaccination rates were computed and compared using Fisher's exact test with statistical significance at P value 0.05 RESULTS: A total of 4443 pregnancies were identified during the study period. The influenza vaccination rate increased in the intervention years at 40.1 per 1000 patient-weeks (P < 0.001), compared to the pre-intervention influenza seasons at 11.7 per 1000 patient-weeks. Vaccine coverage did not statistically differ between pregnancies with or without comorbidities across most seasons. Vaccine coverage decreased as material deprivation increased in pre-intervention years., Conclusion: The vaccination rate was higher in the intervention years compared to the pre-intervention period. In this study, we applied a systematic methodology to examine vaccine coverage in pregnancy and presented a descriptive examination of a POC-VIP intervention., (Copyright © 2024. Published by Elsevier Inc.)

Background: Sepsis is a life-threatening condition but predicting its development and progression remains a challenge., Objective: This study aimed to assess the impact of infection site on sepsis development among emergency department (ED) patients., Methods: Data were collected from a single-center ED between January 2016 and December 2019. Patient encounters with documented infections, as defined by the Systematized Nomenclature of Medicine-Clinical Terms for upper respiratory tract (URI), lower respiratory tract (LRI), urinary tract (UTI), or skin or soft-tissue infections were included. Primary outcome was the development of sepsis or septic shock, as defined by Sepsis-1/2 criteria. Secondary outcomes included hospital disposition and length of stay, blood and urine culture positivity, antibiotic administration, vasopressor use, in-hospital mortality, and 30-day mortality. Analysis of variance and various different logistic regression approaches were used for analysis with URI used as the reference variable., Results: LRI was most associated with sepsis (relative risk ratio [RRR] 5.63; 95% CI 5.07-6.24) and septic shock (RRR 21.2; 95% CI 17.99-24.98) development, as well as hospital admission rates (odds ratio [OR] 8.23; 95% CI 7.41-9.14), intensive care unit admission (OR 4.27; 95% CI 3.84-4.74), in-hospital mortality (OR 6.93; 95% CI 5.60-8.57), and 30-day mortality (OR 7.34; 95% CI 5.86-9.19). UTIs were also associated with sepsis and septic shock development, but to a lesser degree than LRI., Conclusions: Primary infection sites including LRI and UTI were significantly associated with sepsis development, hospitalization, length of stay, and mortality among patients presenting with infections in the ED., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Care bundles are a promising approach to reducing postpartum hemorrhage-related morbidity and mortality. We assessed the effectiveness and safety of care bundles for postpartum hemorrhage prevention and/or treatment., Data Sources: We searched MEDLINE, Embase, Cochrane CENTRAL, Maternity and Infant Care Database, and Global Index Medicus (inception to June 9, 2023) and ClinicalTrials.gov and the International Clinical Trials Registry Platform (last 5 years) using a phased search strategy, combining terms for postpartum hemorrhage and care bundles., Study Eligibility Criteria: Peer-reviewed studies evaluating postpartum hemorrhage-related care bundles were included. Care bundles were defined as interventions comprising ≥3 components implemented collectively, concurrently, or in rapid succession. Randomized and nonrandomized controlled trials, interrupted time series, and before-after studies (controlled or uncontrolled) were eligible., Methods: Risk of bias was assessed using RoB 2 (randomized trials) and ROBINS-I (nonrandomized studies). For controlled studies, we reported risk ratios for dichotomous outcomes and mean differences for continuous outcomes, with certainty of evidence determined using GRADE. For uncontrolled studies, we used effect direction tables and summarized results narratively., Results: Twenty-two studies were included for analysis. For prevention-only bundles (2 studies), low-certainty evidence suggests possible benefits in reducing blood loss, duration of hospitalization, and intensive care unit stay, and maternal well-being. For treatment-only bundles (9 studies), high-certainty evidence shows that the E-MOTIVE intervention reduced risks of composite severe morbidity (risk ratio, 0.40; 95% confidence interval, 0.32-0.50) and blood transfusion for bleeding, postpartum hemorrhage, severe postpartum hemorrhage, and mean blood loss. One nonrandomized trial and 7 uncontrolled studies suggest that other postpartum hemorrhage treatment bundles might reduce blood loss and severe postpartum hemorrhage, but this is uncertain. For combined prevention/treatment bundles (11 studies), low-certainty evidence shows that the California Maternal Quality Care Collaborative care bundle may reduce severe maternal morbidity (risk ratio, 0.64; 95% confidence interval, 0.57-0.72). Ten uncontrolled studies variably showed possible benefits, no effects, or harms for other bundle types. Nearly all uncontrolled studies did not use suitable statistical methods for single-group pretest-posttest comparisons and should thus be interpreted with caution., Conclusion: The E-MOTIVE intervention improves postpartum hemorrhage-related outcomes among women delivering vaginally, and the California Maternal Quality Care Collaborative bundle may reduce severe maternal morbidity. Other bundle designs warrant further effectiveness research before implementation is contemplated., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: A major alcohol-related harm is structural pathology affecting the brain. The study aimed to: 1. Determine the frequency and nature of neuropathology amongst cases of death due to acute alcohol toxicity; 2. Compare diagnoses of brain atrophy with pathology in other organs; 3. Determine the demographic, clinical and organ pathology correlates of brain atrophy., Methods: Retrospective study of 500 cases of death attributed to acute alcohol toxicity in Australia, 2011-2022. Data on clinical characteristics, toxicology, neuropathology and other organ pathology were retrieved from police reports, autopsies, toxicology and coronial findings., Results: Mean age was 49.5 years, 69.4 % were male, with alcohol use problems documented in 70.2 %. Brain atrophy was diagnosed in 60 cases (12.0 %), most commonly in the cerebellum (32 cases, 6.4 %). Atrophy at other sites was present in 37 (7.4 %). The presence of brain atrophy was lower than other major pathologies: cardiomegaly (32.6 %, p<.001), nephro/arteriosclerosis (30.2 %, p<.001), and chronic obstructive pulmonary disease (21.8 %, p<.001) but not hepatic cirrhosis (11.9 % p=1.0). Those diagnosed with atrophy were older (53.4v 49.0 years, p<.001), more likely to have documented alcohol problems (85.0v 68.2 %, Odds ratio: OR 2.53) and seizure history (10.0v 3.0 %, OR 2.92), to have cardiomegaly (43.3v 31.0 %, OR 1.90, COPD (48.3v 18.2 %, 3.57) and nephro/arteriosclerosis (50.0 v 27.4 %, OR 2.27)., Conclusions: Despite the majority of cases having a history of alcohol problems, the level of neuropathology amongst cases of death due to acute alcohol toxicity was comparatively low., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AP has received untied educational grants from Seqirus and Mundipharma for post-marketing surveillance of pharmaceutical opioids. This organisation had no role in study design, analysis and reporting, and funding support was for work unrelated to this project. MF has received untied educational grants from Seqirus, Mundipharma and Indivior for post-marketing surveillance of pharmaceutical opioids. This organisation had no role in study design, analysis and reporting, and funding support was for work unrelated to this project. AP is funded by an NHMRC Investigator Fellowship., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: To evaluate the risk of bias due to missing evidence in a sample of published meta-analyses of nutrition research using the Risk Of Bias due to Missing Evidence (ROB-ME) tool and determine inter-rater agreement in assessments., Study Design and Setting: We assembled a random sample of 42 meta-analyses of nutrition research. Eight assessors were randomly assigned to one of four pairs. Each pair assessed 21 randomly assigned meta-analyses, and each meta-analysis was assessed by two pairs. We calculated raw percentage agreement and chance corrected agreement using Gwet's Agreement Coefficient (AC) in consensus judgments between pairs., Results: Across the eight signaling questions in the ROB-ME tool, raw percentage agreement ranged from 52% to 100%, and Gwet's AC ranged from 0.39 to 0.76. For the risk-of-bias judgment, the raw percentage agreement was 76% (95% confidence interval 60% to 92%) and Gwet's AC was 0.47 (95% confidence interval 0.14 to 0.80). In seven (17%) meta-analyses, either one or both pairs judged the risk of bias due to missing evidence as "low risk"., Conclusion: Our findings indicated substantial variation in assessments in consensus judgments between pairs for the signaling questions and overall risk-of-bias judgments. More tutorials and training are needed to help researchers apply the ROB-ME tool more consistently., Competing Interests: Declaration of Competing Interest MJP is an editorial board member for the Journal of Clinical Epidemiology. MJP led and JEM and RK contributed to the development of the ROB-ME tool., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Body dysmorphic disorder (BDD) is characterised by a preoccupation with a perceived defect in appearance. This preoccupation results in the completion of repetitive/time consuming behaviours to reduce distress. While the disorder results in considerable distress and impairment, the prevalence of the disorder is largely unknown, as BDD has not been examined in large epidemiological studies. The aim of the current study was to provide an estimate of BDD prevalence in a variety of settings using a meta-analytic approach using only studies that have made a diagnosis using a structured diagnostic interview. Twenty-two studies met criteria (n = 7159) and the pooled point-prevalence estimate for BDD was 11.3% across all studies with high levels of heterogeneity (I 2 = 95.81). The pooled point-prevalence estimate was 20.0% in cosmetic/dermatology settings, 7.4% in mental health settings, and 6.7% in 'other' settings (including students and professional ballet dancers). The risk of bias assessment indicated questionable methodological quality in some of the included studies. While this study provides an important improvement on the existing literature there is a need to include BDD in epidemiological studies in order to have a more accurate understanding of the prevalence rate of this mental health condition in the community., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: There is a lack of consensus about the effect of the COVID-19 pandemic on the mental health of children and adolescents. We aimed to compare rates of paediatric emergency department visits for attempted suicide, self-harm, and suicidal ideation during the pandemic with those before the pandemic., Methods: For this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO for studies published between Jan 1, 2020, and Dec 19, 2022. Studies published in English with data on paediatric (ie, those aged <19 years) emergency department visits before and during the COVID-19 pandemic were included. Case studies and qualitative analyses were excluded. Changes in attempted suicide, self-harm, suicidal ideation, and other mental-illness indicators (eg, anxiety, depression, and psychosis) were expressed as ratios of the rates of emergency department visits during the pandemic compared with those before the pandemic, and we analysed these with a random-effects meta-analysis. This study was registered with PROSPERO, CRD42022341897., Findings: 10 360 non-duplicate records were retrieved, which yielded 42 relevant studies (with 130 sample-estimates) representing 11·1 million emergency department visits for all indications of children and adolescents across 18 countries. The mean age of the samples of children and adolescents across studies was 11·7 years (SD 3·1, range 5·5-16·3), and there were on average 57·6% girls and 43·4% boys as a proportion of emergency department visits for any health reasons (ie, physical and mental). Only one study had data related to race or ethnicity. There was good evidence of an increase in emergency department visits for attempted suicide during the pandemic (rate ratio 1·22, 90% CI 1·08-1·37), modest evidence of an increase in emergency department visits for suicidal ideation (1·08, 0·93-1·25), and good evidence for only a slight change in self-harm (0·96, 0·89-1·04). Rates of emergency department visits for other mental-illness indications showed very good evidence of a decline (0·81, 0·74-0·89), and paediatric visits for all health indications showed strong evidence of a reduction (0·68, 0·62-0·75). When rates for attempted suicide and suicidal ideation were combined as a single measure, there was good evidence of an increase in emergency department visits among girls (1·39, 1·04-1·88) and only modest evidence of an increase among boys (1·06, 0·92-1·24). Self-harm among older children (mean age 16·3 years, range 13·0-16·3) showed good evidence of an increase (1·18, 1·00-1·39), but among younger children (mean age 9·0 years, range 5·5-12·0) there was modest evidence of a decrease (0·85, 0·70-1·05)., Interpretation: The integration of mental health support within community health and the education system-including promotion, prevention, early intervention, and treatment-is urgently needed to increase the reach of mental health support that can mitigate child and adolescent mental distress. In future pandemics, increased resourcing in some emergency department settings would help to address their expected increase in visits for acute mental distress among children and adolescents., Funding: None., Competing Interests: Declaration of interests TV has received honoraria for presentations related to youth suicide during the pandemic and is also the Chair of the COVID-19 Task Force and the Children and Schools working group for the Royal Society of Canada and is the President of the International Society for Research on Aggression. DJK has received grant funding related to research on youth suicide from the Canadian Institutes of Health Research, Sobey's Foundation, and SickKids Foundation in the past 36 months. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: To introduce methods for living guidelines based on practical experiences by the Australian Living Evidence Consortium (ALEC), the National Institute of Health and Care Excellence (NICE), and the Infectious Diseases Society of America (IDSA), with methodological support from the US Grading of Recommendations, Assessment, Development and Evaluations (GRADE) Network., Study Design and Setting: Members of ALEC, NICE, and the US GRADE Network, convened a working group to share experiences of the methods used to develop living guidelines and outline the key differences between traditional and living guidelines methods., Results: The guidance includes the following steps: 1) deciding if the guideline is a priority for a living approach, 2) preparing for living guideline development, 3) literature surveillance and frequency of searching, 4) assessment and synthesis of the evidence, 5) publication and dissemination, and 6) transitioning recommendations out of living mode., Conclusion: This paper introduces methods for living guidelines and provides examples of the similarities and differences in approach across multiple organizations conducting living guidelines. It also introduces a series of papers exploring methods for living guidelines based on our practical experiences, including consumer involvement, selecting and prioritizing questions, search decisions, and methods decisions., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To describe the key features of a continual evidence surveillance process that can be implemented for living guidelines and to outline the considerations and trade-offs in adopting different approaches., Study Design and Setting: Members of the Australian Living Evidence Consortium (ALEC), National Institute of Health and Care Excellence (NICE), and the US GRADE Network (USGN) shared their practical experiences of and approaches to establishing surveillance systems for living guidelines. We identified several common components of evidence surveillance and listed the key features and considerations for each component drawn from case studies, highlighting differences with standard guidelines., Results: We developed guidance that covers the initial information needed to support decisions around suitability for living mode and the practical considerations in setting up continual search surveillance systems (search frequency, sources to search, use of automation, reporting the search, ongoing resources, and evaluation). The case studies draw on our experiences with developing guidelines for COVID-19, as well as for other conditions such as stroke and diabetes, and cover a range of practical approaches, including the use of automation., Conclusion: This paper highlights different approaches to continual evidence surveillance that can be implemented in living guidelines., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate how quickly evidence was incorporated into the Australian living guidelines for COVID-19 during the first 12 months of the pandemic., Study Design and Setting: For each study concerning drug therapies included in the guideline from April 3, 2020 to April 1, 2021, we extracted the publication date of the study, and the guideline version the study was included in. We analyzed two subgroups of studies as follows: those published in high impact factor journals and those with 100 or more participants., Results: In the first year, we published 37 major versions of the guidelines, incorporating 129 studies that investigated 48 drug therapies informing 115 recommendations. The median time from first publication of a study to incorporation in the guideline was 27 days (interquartile range [IQR], 16 to 44), ranging from 9 to 234 days. For the 53 studies in the highest impact factor journals, the median was 20 days (IQR 15 to 30), and for the 71 studies with 100 or more participants the median was 22 days (IQR 15 to 36)., Conclusion: Developing and sustaining living guidelines where evidence is rapidly incorporated is a resource- and time-intensive undertaking; however, this study demonstrates that it is feasible, even over a long period., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To describe a process of meaningful Aboriginal community engagement that repositioned and valued community members' knowledge(s) and lived experiences while strengthening relationships, research processes and outcomes., Background: Aboriginal Australians have the oldest continuous culture in the world, yet due to effects of colonisation, experience some of the world's poorest health outcomes. The AKction [Aboriginal Kidney Care Together - Improving Outcomes Now] project brought together Aboriginal people with lived experience of kidney disease, clinicians and researchers to improve kidney care., Methodology: Using Aboriginal methodologies of Ganma and Dadirri within community-based participatory action research (cb-PAR), a core advisory group of Aboriginal people with lived experiences of kidney disease worked closely with clinicians and researchers., Results: Three community consultation workshops that deeply valued Aboriginal knowledge(s) were co-created. Community members formed a reference group, established partnerships and influenced health research, policy and service provision. Non-Indigenous researchers engaged in critical self-reflection and levelling of Western-Aboriginal and clinician-consumer power imbalances., Conclusions: Deeply respectful community engagement is possible through co-creation and cb-PAR. It results in multiple positive impacts and beneficial relationships between community members, clinicians and academics., Implications for Public Health: Meaningful consultation with Aboriginal communities guides culturally safe research processes, health policy and service delivery., (© 2022 The Authors.)

Objective: To describe the experiences, perceptions and suggested improvements in healthcare identified by Aboriginal patients, families and community members living with kidney disease in South Australia., Methods: Community consultations were held in an urban, rural and remote location in 2019 by the Aboriginal Kidney Care Together - Improving Outcomes Now (AKction) project and Kidney Health Australia. Consultations were co-designed with community members, using participatory action research, Yarning, Dadirri and Ganma Indigenous Methodologies. Key themes were synthesised, verified by community members and shared through formal and community reports and media., Results: Aboriginal participants identified the importance of: family and community and maintaining their wellbeing, strength and resilience; the need for prevention and early detection that is localised, engages whole families and prevents diagnosis shock; better access to quality care that ensures Aboriginal people can make informed choices and decisions about their options for dialysis and transplantation, and; more Aboriginal health professionals and peer navigators, and increased responsiveness and provision of cultural safety care by all kidney health professionals., Conclusion: Aboriginal community members have strong and clear recommendations for improving the quality and responsiveness of health care generally, and kidney care specifically., Implications for Public Health: Aboriginal people with lived experience of chronic conditions wish to significantly inform the way care is organised and delivered., (© 2022 The Authors.)

Purpose: According to the social determinants of health framework, income inequality is a potential risk factor for adverse mental health. However, few studies have explored the mechanisms suspected to mediate this relationship. The current study addresses this gap through a mediation analysis to determine if social support and community engagement act as mediators linking neighbourhood income inequality to maternal anxiety and depressive symptoms within a cohort of new mothers living in the City of Calgary, Canada., Methods: Data collected at three years postpartum from mothers belonging to the All Our Families (AOF) cohort were used in the current study. Maternal data were collected between 2012 and 2015 and linked to neighbourhood socioeconomic data from the 2006 Canadian Census. Income inequality was measured using Gini coefficients derived from 2006 after-tax census data. Generalized structural equation models were used to quantify the associations between income inequality and mental health symptoms, and to assess the potential direct and indirect mediating effects of maternal social support and community engagement., Results: Income inequality was not significantly associated with higher depressive symptoms (β = 0.32, 95%CI = -0.067, 0.70), anxiety symptoms (β = 0.11, 95%CI = -0.39, 0.60), or lower social support. Income inequality was not associated with community engagement. For the depression models, higher social support was significantly associated with lower depressive symptoms (β = -0.13, 95%CI = -0.15, -0.097), while community engagement was not significantly associated with depressive symptoms (β = 0.059, 95%CI = -0.15, 0.27). Similarly, for the anxiety models, lower anxiety symptoms were significantly associated with higher levels of social support (β = -0.17, 95%CI = -0.20, -0.13) but not with higher levels of community engagement (β = 0.14, 95%CI = -0.14, 0.41)., Conclusion: The current study did not find clear evidence for social support or community engagement mediating the relationship between neighbourhood income inequality and maternal mental health. Future investigations should employ a broader longitudinal approach to capture changes in income inequality, potential mediators, and mental health symptomatology over time., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: COVID-19 has been associated with increased risk of thromboembolism in critically ill patients., Objective: We sought to examine the association of SARS-CoV-2 test positivity and subsequent acute vascular thrombosis, including venous thromboembolism (VTE) or arterial thrombosis (AT), in a large nationwide registry of emergency department (ED) patients tested with a nucleic acid test for suspected SARS-CoV-2., Methods: The RECOVER (Registry of Potential COVID-19 in Emergency Care) registry includes 155 EDs across the United States. We performed a retrospective cohort study to produce odds ratios (ORs) for COVID-19-positive vs. COVID-19-negative status as a predictor of 30-day VTE or AT, adjusting for age, sex, active cancer, intubation, hospital length of stay, and intensive care unit (ICU) care., Results: Comparing 14,056 COVID-19-positive patients with 12,995 COVID-19-negative patients, the overall 30-day prevalence of VTE events was 1.4% vs. 1.3%, respectively (p = 0.44, χ 2 ). Multivariable analysis identified that testing positive for SARS-CoV-2 status was negatively associated with both VTE (OR 0.76; 95% confidence interval [CI] 0.61-0.94) and AT (OR 0.51; 95% CI 0.32-0.80), whereas intubation, ICU care, and age 50 years or older were positively associated with both VTE and AT., Conclusions: In contrast to other reports, results from this large, hetereogenous national sample of ED patients tested for SARS-CoV-2, showed no association between vascular thrombosis and COVID-19 test positivity., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To investigate the completeness and currency of published systematic reviews of remdesivir for COVID-19 and to compare this with a living guidelines approach., Study Design and Setting: In this cross-sectional study, we searched Europe PMC on May 20, 2021 for systematic reviews of remdesivir (including preprints, living review updates). Completeness and currency were based on the inclusion of four major randomized trials of remdesivir available at the time of publication of the review (including as preliminary results and preprints)., Results: We included 38 reviews (45 reports), equivalent to a new publication every 9 days. 23 (51%) reports were out of date at the time of publication. Eleven reviews that were current on publication had a median survival time of 10 days (range 4-57). A third of reviews cited other systematic reviews, but only four provided justifications for why another review was necessary. Eight (21%) of the reviews were registered in PROSPERO. The Australian COVID-19 Clinical Evidence Taskforce living guidelines were updated within 14 days for three of the remdesivir trials, and within 28 days for the fourth., Conclusion: There was considerable duplication of systematic reviews of remdesivir, and half were already out of date at the time of publication., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Meta-research is the discipline of studying research itself. A core investigative tool in meta-research is the use of systematic or scoping reviews to study the characteristics, methods and reporting of primary research studies. In the context of identifying eligible publications for methodological reviews of randomized controlled trials (RCTs), a challenge is to efficiently distinguish the primary trial report - which reports results for the primary outcome - from other types of reports, including design papers and secondary or supplementary analyses, or what we collectively refer to as non-primary reports. This may not be a straightforward task and may contribute to inefficiencies in the review process. Here, we draw on our recent methodological review of over 13,000 records to identify primary reports of pragmatic RCTs. We offer recommendations to improve the reporting of RCTs to facilitate more efficient identification of primary trial reports. We suggest that future updates to existing CONSORT guidelines include consideration of multiple trial reports and recommendations to clarify the primary or non-primary nature of each report. Our recommendations, together with improved adherence to inclusion of the trial registration number in the abstract and citation of a protocol or previously published primary report, would facilitate the conduct of methodological reviews., (Copyright © 2022. Published by Elsevier Inc.)

Background: Millions of people have acquired and died from SARS-CoV-2 infection during the COVID-19 pandemic. Healthcare workers (HCWs) are required to wear personal protective equipment (PPE), including surgical masks and P2/N95 respirators, to prevent infection while treating patients. However, the comparative effectiveness of respirators and masks in preventing SARS-CoV-2 infection and the likelihood of experiencing adverse events (AEs) with wear are unclear., Methods: Searches were carried out in PubMed, Europe PMC and the Cochrane COVID-19 Study Register to 14 June 2021. A systematic review of comparative epidemiological studies examining SARS-CoV-2 infection or AE incidence in HCWs wearing P2/N95 (or equivalent) respirators and surgical masks was performed. Article screening, risk of bias assessment and data extraction were duplicated. Meta-analysis of extracted data was carried out in RevMan., Results: Twenty-one studies were included, with most having high risk of bias. There was no statistically significant difference in respirator or surgical mask effectiveness in preventing SARS-CoV-2 infection (OR 0.85, [95%CI 0.72, 1.01]). Healthcare workers experienced significantly more headaches (OR 2.62, [95%CI 1.18, 5.81]), respiratory distress (OR 4.21, [95%CI 1.46, 12.13]), facial irritation (OR 1.80, [95%CI 1.03, 3.14]) and pressure-related injuries (OR 4.39, [95%CI 2.37, 8.15]) when wearing respirators compared to surgical masks., Conclusion: The existing epidemiological evidence does not enable definitive assessment of the effectiveness of respirators compared to surgical masks in preventing infection. Healthcare workers wearing respirators may be more likely to experience AEs. Effective mitigation strategies are important to ensure the uptake and correct use of respirators by HCWs., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Deceased donor kidneys are a scarce community resource; therefore, the principles underpinning organ allocation should reflect societal values. This study aimed to elicit community and healthcare professional preferences for principles guiding the allocation of kidneys from deceased donors and compare how these differed across the populations. A best-worst scaling survey including 29 principles in a balanced incomplete block design was conducted among a representative sample of the general community (n = 1237) and healthcare professionals working in transplantation (n = 206). Sequential best-worst multinomial logistic regression was used to derive scaled preference scores (PS) (range 0-100). Thematic analysis of free text responses was performed. Five of the six most valued principles among members of the community related to equity, including priority for the longest waiting (PS 100), difficult to transplant (PS 94.5) and sickest (PS 93.9), and equitable access for men and women (PS 94.0), whereas the top four principles for healthcare professional focused on maximizing utility (PS 89.9-100). Latent class analysis identified unmeasured class membership among community members. There are discordant views between community members and healthcare professionals. These should be considered in the design, evaluation, and implementation of deceased donor kidney allocation protocols., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objectives: To investigate how often review authors encounter multiple results from included studies that are eligible for inclusion in a particular meta-analysis, and how often methods to select results are specified., Methods: MEDLINE and Epistemonikos were searched (January 2018-June 2019) to identify systematic reviews with meta-analysis of the association between food/diet and health-related outcomes. A random sample of these reviews was selected, and for the first presented (index) meta-analysis, rules used to select effect estimates to include in this meta-analysis were extracted from the reviews and their protocols. All effect estimates from the primary studies that were eligible for inclusion in the index meta-analyses were extracted (e.g., when a study report presented effect estimates for blood pressure at 3 weeks and 6 weeks, both unadjusted and adjusted for covariates, and all were eligible for inclusion in a meta-analysis of the effect of red meat consumption on blood pressure, we extracted all estimates, and classified the study as having "multiplicity of results")., Results: Forty-two systematic reviews with 325 studies (104 randomized, 221 non-randomized) were included; 14 reviews had a protocol. In 29% of review protocols and 69% of reviews, authors specified at least one decision rule to select effect estimates when multiple were available. In 68% of studies included in the index meta-analyses, there was at least one type of multiplicity of results., Conclusions: Authors of systematic reviews of nutrition studies should anticipate encountering multiplicity of results in the included primary studies. Specification of methods to handle multiplicity when designing reviews is therefore recommended., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Maintaining clinical guideline currency has been one challenge to traditional guideline development. This paper describes the methods used to maintain a large national guideline for stroke management., Study Design and Setting: The Australian Stroke Clinical Guidelines are developed to meet Australian National Health and Medical Research Council (NHMRC) standards. Monthly surveillance is conducted for new systematic reviews and randomised controlled studies. Included studies undergo data extraction followed by preparation of updated evidence-to-decision frameworks which are used to inform updates, or development of new recommendations. Small writing groups made up of clinical experts and those with lived experience review and agree on changes, which are finally reviewed by a multidisciplinary Guidelines Steering Group. Draft changes are developed and published using the online MAGICapp platform, with dissemination and promotion via traditional methods as well as social media., Results: Each month approximately 350 abstracts are considered, covering 96 clinical topics and taking on average 16 h to review. There have been four major guideline updates covering 34 new and updated recommendations., Conclusion: It is feasible to use 'living' methods to maintain the Australian Clinical Guidelines for Stroke Management. Further work is now needed to understand the impact of living guidelines., Competing Interests: Conflicts of interest declaration Kelvin Hill -program manager for lead agency, no other conflicts of interest Coralie English -co-chair of the guidelines content team, no other conflicts of interest Bruce C.V. Campbell -co-chair of the guidelines content team, no other conflicts of interest Steve McDonald - involved in Cochrane living methods, no other conflicts of interest Loyal Pattuwage -no conflicts of interest Peta Bates -no conflicts of interest Chris Lassig -no conflicts of interest Tari Turner -involved in Cochrane living methods, no other conflicts of interest, (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Clinical detection and management of chorioamnionitis is challenging given the gold-standard for diagnosis remains placental pathology, the results of which are only available after delivery. Moreover, recommended diagnostic criteria for clinical chorioamnionitis have evolved over time. The goal of this study was to describe trends and differences in chorioamnionitis diagnostic and management practices in Canada., Methods: We surveyed obstetric care providers participating in the Canadian Preterm Birth Network. Questionnaires were distributed electronically to all 29 sites and completed by 1 maternal-fetal medicine investigator at each site., Results: The response rate was 82.8% (n = 24). There was considerable variation in the clinical criteria used to diagnose chorioamnionitis with 9 of 22 sites stating this occurs "frequently" or "very frequently." Isolated fever was "always" or "most of the time" used as an indication to start empiric antibiotic therapy in 14 of 24 sites, and 21 of 23 sites used the same diagnostic criteria for term and preterm deliveries. Placental histology (15 sites) and white blood cell count (14 sites) were the most common clinical tests performed to confirm chorioamnionitis. A combination of ampicillin and aminoglycoside antibiotics was used at 12 sites. Another frequently used antibiotic therapy was cefazolin and metronidazole (4 sites)., Conclusion: There is a wide variation in practices for the diagnosis and management of chorioamnionitis across Canada. The results of this study will guide efforts to improve and standardize the management of this condition., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)