Stages of Valvular Heart Disease Among Older Adults in the Community: The Atherosclerosis Risk in Communities Study.

BACKGROUND: Limited data exist on American College of Cardiology/American Heart Association valvular heart disease (VHD) stage prevalence, progression, and association with incident cardiovascular diseases in late life. METHODS: Participants in the ARIC study (Atherosclerosis Risk in Communities), a prospective community-based cohort study, underwent protocol echocardiography at ARIC visits 5 (2011-2013) and 7 (2018-2019), and their aortic stenosis, aortic regurgitation, mitral stenosis, and mitral regurgitation stage were defined according to American College of Cardiology/American Heart Association guidelines. The overall VHD stage prevalence at visit 5 was measured. The associations between VHD stages and incident adjudicated death, heart failure, coronary heart disease, stroke, and atrial fibrillation were assessed with Cox proportional hazard models adjusted for age, sex, race, hypertension, diabetes, prior myocardial infarction, heart failure, body mass index, study center, systolic blood pressure, estimated glomerular filtration rate, and low-density lipoprotein at visit 5. Longitudinal changes in VHD stage prevalence over ≈6 years were estimated with inverse probability of attrition weights to account for participant attrition. RESULTS: Among 6118 ARIC participants, the mean±SD age was 76±5 years, 42% were male, and 22% reported Black race. Stage A VHD was present in 39%, stage B in 17%, and stage C/D in 1.1%;, 0.7% had previously undergone valve replacement or repair. A graded association was observed between stage A, B, and C/D VHD and risk of all-cause mortality, incident heart failure, incident atrial fibrillation, and incident coronary heart disease, but not incident stroke. Similar findings were observed for stages of each valvular lesion individually. During the 6.6 years (interquartile range, 6.1-7.0 years) between visits 5 and 7 (mean age, 81±4 years), the prevalence of freedom from VHD stage decreased from 43% to 24%, whereas the prevalence of stage C/D VHD increased from 1% to 7%. CONCLUSIONS: Subclinical VHD is common in older adults, with 39% at risk (stage A) and 17% with progressive VHD (stage B), and is independently associated with risk of incident cardiovascular events. VHD stages progress over 6 years in late life, with a several-fold increase in prevalence of severe VHD (stage C/D), highlighting the public health importance of interventions to mitigate VHD progression.

Management of low-level HIV viremia during antiretroviral therapy: Delphi consensus statement and appraisal of the evidence.

OBJECTIVE: While antiretroviral therapy (ART) is highly effective, detection of low levels of HIV-1 RNA in plasma is common in treated individuals. Given the uncertainties on the topic, we convened a panel of experts to consider different clinical scenarios, producing a Delphi consensus to help guide clinical practice. METHODS: A panel of 17 experts in infectious diseases, virology and immunology rated 32 statements related to four distinct scenarios: (1) low-level viremia during stable (≥6 months) first-line ART (≥2 consecutive HIV-1 RNA measurements 50-500 copies/mL); (2) a viral blip during otherwise suppressive ART (a HIV-1 RNA measurement 50-1000 copies/mL with adjacent measurements <50 copies/mL); (3) low-level viral rebound during previously suppressive ART (≥2 consecutive HIV-1 RNA measurements 50-500 copies/mL); (4) residual viremia during suppressive ART (persistent HIV-1 RNA quantification below 50 copies/mL). A systematic review, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement, informed the 32 statements. The Delphi procedure was modified to include two voting rounds separated by a moderated group discussion. Grading of Recommendations, Assessment, Development, and Evaluations-based recommendations were developed. RESULTS: Overall, 18/32 statements (56.2%) achieved a strong consensus, 3/32 (9.4%) achieved a moderate consensus and 11/32 (34.4%) did not achieve a consensus. Across the four scenarios, the panel unanimously emphasised the importance of implementing specific interventions prior to considering therapy changes, including assessing adherence, testing for genotypic drug resistance and scheduling more frequent follow-up visits. Strategies indicated in selected circumstances included therapeutic drug monitoring, quantifying total HIV-1 DNA and evaluating concomitant chronic infections. CONCLUSIONS: While acknowledging the many uncertainties about source, significance and optimal management of low-level viremia during ART, the findings provide insights to help harmonise clinical practice. There is a need for well-designed randomised studies assessing different interventions to manage low-level viremia and future research regarding its definition.

Clinical practice guidelines on the management of status epilepticus in adults: A systematic review.

OBJECTIVE: Status epilepticus (SE) is the second most common neurological emergency in adults. Despite improvements in the management of acute neurological conditions over the last decade, mortality is still durably high. Because a gap has emerged between SE management based on clinical practice guidelines (CPGs) and actual clinical practice, we conducted a systematic review of CPGs, assessing their quality, outlining commonalities and discrepancies in recommendations, and highlighting research gaps. METHODS: We searched the PubMed and EMBASE databases and other gray literature sources (nine among guideline registries, evidence-based medicine databases, point-of-care tools; seven websites of governmental organizations and international neurologic societies) in December 2021 (updated in November 2023). The units of analysis were CPGs that included recommendations on the diagnostic and/or therapeutic management of SE in adults. The quality of the CPGs was assessed using the AGREE II tool. RESULTS: Fifteen CPGs were included. The "Applicability" domain was assigned the lowest median score of 10%. The domains "Stakeholder Involvement", "Rigor of Development," and "Editorial Independence" were as well generally underrated. Recommendations on general and diagnostic management and on organizational interventions were fragmented and scattered. Recommendations on pre-hospital and hospital treatment of early-onset and refractory SE were broadly agreed, whereas there was less agreement on the treatment model and medications for established SE and super-refractory SE. SIGNIFICANCE: The CPGs for the management of SE developed in recent years are flawed by several methodological issues and discrepancies in the coverage of important topics. The gap between CPG-based management of SE and actual clinical practice may be due in part to the inherent limitations of the CPGs produced so far.

Designing tailored maintenance strategies for systematic reviews and clinical practice guidelines using the Portfolio Maintenance by Test-Treatment (POMBYTT) framework.

BACKGROUND: Organizations face diverse contexts and requirements when updating and maintaining their portfolio, or pool, of systematic reviews or clinical practice guidelines they need to manage. We aimed to develop a comprehensive, theoretical framework that might enable the design and tailoring of maintenance strategies for portfolios containing systematic reviews and guidelines. METHODS: We employed a conceptual approach combined with a literature review. Components of the diagnostic test-treatment pathway used in clinical healthcare were transferred to develop a framework specifically for systematic review and guideline portfolio maintenance strategies. RESULTS: We developed the Portfolio Maintenance by Test-Treatment (POMBYTT) framework comprising diagnosis, staging, management, and monitoring components. To illustrate the framework's components and their elements, we provided examples from both a clinical healthcare test-treatment pathway and a clinical practice guideline maintenance scenario. Additionally, our literature review provided possible examples for the elements in the framework, such as detection variables, detection tests, and detection thresholds. We furthermore provide three example strategies using the framework, of which one was based on living recommendations strategies. CONCLUSIONS: The developed framework might support the design of maintenance strategies that could contain multiple options besides updating to manage a portfolio (e.g. withdrawing and archiving), even in the absence of the target condition. By making different choices for variables, tests, test protocols, indications, management options, and monitoring, organizations might tailor their maintenance strategy to suit specific contexts and needs. The framework's elements could potentially aid in the design by being explicit about the operational aspects of maintenance strategies. This might also be helpful for end-users and other stakeholders of systematic reviews and clinical practice guidelines.

Cough in Children and Adults: Diagnosis, Assessment and Management (CICADA). Summary of an updated position statement on chronic cough in Australia.

INTRODUCTION: Cough is the most common symptom leading to medical consultation. Chronic cough results in significant health care costs, impairs quality of life, and may indicate the presence of a serious underlying condition. Here, we present a summary of an updated position statement on cough management in the clinical consultation. MAIN RECOMMENDATIONS: Assessment of children and adults requires a focused history of chronic cough to identify any red flag cough pointers that may indicate an underlying disease. Further assessment with examination should include a chest x-ray and spirometry (when age > 6 years). Separate paediatric and adult diagnostic management algorithms should be followed. Management of the underlying condition(s) should follow specific disease guidelines, as well as address adverse environmental exposures and patient/carer concerns. First Nations adults and children should be considered a high risk group. The full statement from the Thoracic Society of Australia and New Zealand and Lung Foundation Australia for managing chronic cough is available at https://lungfoundation.com.au/resources/cicada-full-position-statement. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: Algorithms for assessment and diagnosis of adult and paediatric chronic cough are recommended. High quality evidence supports the use of child-specific chronic cough management algorithms to improve clinical outcomes, but none exist in adults. Red flags that indicate serious underlying conditions requiring investigation or referral should be identified. Early and effective treatment of chronic wet/productive cough in children is critical. Culturally specific strategies for facilitating the management of chronic cough in First Nations populations should be adopted. If the chronic cough does not resolve or is unexplained, the patient should be referred to a respiratory specialist or cough clinic.

National Health and Medical Research Council statement on electronic cigarettes: 2022 update.

INTRODUCTION: Electronic cigarette (e-cigarette) use in Australia has rapidly increased since the 2017 National Health and Medical Research Council (NHMRC) Chief Executive Officer (CEO) statement on e-cigarettes. The type of products available and the demographic characteristics of people using these products have changed. New evidence has been published and there is growing concern among public health professionals about the increased use, particularly among young people who do not currently smoke combustible cigarettes. The combination of these issues led NHMRC to review the current evidence and provide an updated statement on e-cigarettes. In this article, we describe the comprehensive process used to review the evidence and develop the 2022 NHMRC CEO statement on electronic cigarettes. MAIN RECOMMENDATIONS: E-cigarettes can be harmful; all e-cigarette users are exposed to chemicals and toxins that have the potential to cause adverse health effects. There are no health benefits of using e-cigarettes if you do not currently smoke tobacco cigarettes. Adolescents are more likely to try e-cigarettes if they are exposed to e-cigarettes on social media. Short term e-cigarette use may help some smokers to quit who have been previously unsuccessful with other smoking cessation aids. There are other proven safe and effective options available to help smokers to quit. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: The evidence base for the harms of e-cigarette use has strengthened since the previous NHMRC statement. Significant gaps in the evidence base remain, especially about the longer term health harms of using e-cigarettes and the toxicity of many chemicals in e-cigarettes inhaled as an aerosol.

A summary of the 2023 Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) hypertension in pregnancy guideline.

INTRODUCTION: Hypertensive disorders of pregnancy (HDP) affect up to 10% of all pregnancies annually and are associated with an increased risk of maternal and fetal morbidity and mortality. This guideline represents an update of the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) guidelines for the management of hypertensive disorders of pregnancy 2014 and has been approved by the National Health and Medical Research Council (NHMRC) under section 14A of the National Health and Medical Research Council Act 1992. In approving the guideline recommendations, NHMRC considers that the guideline meets NHMRC's standard for clinical practice guidelines. MAIN RECOMMENDATIONS: A total of 39 recommendations on screening, preventing, diagnosing and managing HDP, especially preeclampsia, are presented in this guideline. Recommendations are presented as either evidence-based recommendations or practice points. Evidence-based recommendations are presented with the strength of recommendation and quality of evidence. Practice points were generated where there was inadequate evidence to develop specific recommendations and are based on the expertise of the working group. CHANGES IN MANAGEMENT RESULTING FROM THE GUIDELINE: This version of the SOMANZ guideline was developed in an academically robust and rigorous manner and includes recommendations on the use of combined first trimester screening to identify women at risk of developing preeclampsia, 14 pharmacological and two non-pharmacological preventive interventions, clinical use of angiogenic biomarkers and the long term care of women who experience HDP. The guideline also includes six multilingual patient infographics which can be accessed through the main website of the guideline. All measures were taken to ensure that this guideline is applicable and relevant to clinicians and multicultural women in regional and metropolitan settings in Australia and New Zealand.

Adherence to clinical care standards and mortality after hip fracture surgery in New South Wales, 2015-2018: a retrospective population-based study.

OBJECTIVES: To determine whether adherence to hip fracture clinical care quality indicators influences mortality among people who undergo surgery after hip fracture in New South Wales, both overall and by individual indicator. STUDY DESIGN: Retrospective population-based study; analysis of linked Australian and New Zealand Hip Fracture Registry (ANZHFR), hospital admissions, residential aged care, and deaths data. SETTING, PARTICIPANTS: People aged 50 years or older with hip fractures who underwent surgery in 21 New South Wales hospitals participating in the ANZHFR, 1 January 2015 - 31 December 2018. MAIN OUTCOME MEASURES: Thirty-day (primary outcome), 120-day, and 365-day mortality (secondary outcomes) by clinical care indicator adherence level (low: none to three of six indicators achieved; moderate: four indicators achieved; high: five or six indicators achieved) and by individual indicator. RESULTS: Registry data were available for 9236 hip fractures in 9058 people aged 50 years or older during 2015-2018; the mean age of patients was 82.8 years (standard deviation, 9.3 years), 5510 patients were women (69.4%). Complete data regarding adherence to clinical care indicators were available for 7951 fractures (86.1%); adherence to these indicators was high for 5135 (64.6%), moderate for 2249 (28.3%), and low for 567 fractures (7.1%). After adjustment for age, sex, comorbidity, admission year, pre-admission walking ability, and residential status, 30-day mortality risk was lower for high (adjusted relative risk [aRR], 0.40; 95% confidence interval [CI], 0.30-0.52) and moderate indicator adherence hip fractures (aRR, 0.61; 95% CI, 0.46-0.82) than for low indicator adherence hip fractures, as was 365-day mortality (high adherence: aRR, 0.59 [95% CI, 0.51-0.68]; moderate adherence: aRR, 0.74 [95% CI, 0.63-0.86]). Orthogeriatric care (365 days: aRR, 0.78; 95% CI, 0.61-0.98) and offering mobilisation by the day after surgery (365 days: aRR, 0.74; 95% CI, 0.67-0.83) were associated with lower mortality risk at each time point. CONCLUSIONS: Clinical care for two-thirds of hip fractures attained a high level of adherence to the six quality care indicators, and short and longer term mortality was lower among people who received such care than among those who received low adherence care.

Real-world treatment of metastatic hormone-sensitive prostate cancer in the USA, Europe and Asia.

Aim: To characterize real-world patients with metastatic hormone-sensitive prostate cancer (mHSPC) and treating physicians and evaluate treatment trends and baseline concordance versus guidelines internationally. Materials & methods: Retrospective, cross-sectional data from the Ipsos Global Oncology Monitor database 2018-2020 were used for descriptive analysis of mHSPC patients, treating physicians and treatment utilization. Results: Among the 6198 mHSPC patients from five countries, the most common treatment was either androgen deprivation therapy (ADT) monotherapy or first-generation androgen receptor inhibitor + ADT. Second-generation androgen receptor inhibitor use was only initiating but increasing over the study period. Conclusion: Despite contemporaneous guidelines recommending treatment intensification of ADT in combination with novel antihormonals or docetaxel, 76.1% of reported mHSPC patients received non-guideline-concordant care.

Prostate cancer is the second most common cancer among men worldwide and a leading cause of cancer-related death globally. Metastatic hormone-sensitive prostate cancer (mHSPC) refers to the stage of prostate cancer where it has spread to other parts of the body ('metastatic') but still responds to hormonal therapy ('hormone-sensitive'), such as androgen deprivation therapy (ADT). Treatment guidelines around the world for men with mHSPC have changed over time, but there remains a lack of understanding of how well guidelines are followed in real-world practice. Consequently, this study analyzes real-world data from five countries between 2018 and 2020 to understand treatment patterns, baseline concordance versus guidelines and potential drivers of treatment trends. The study found prevalent use of ADT monotherapy and older antihormonal agents, and only marginal but increasing use of novel antihormonals in real-world practice. These practices deviate from guidelines from the study period, which generally recommended ADT combination with either newer antihormonal agents or docetaxel for patients with mHSPC. Overall, the proportion of the 6198 patients treated with non­guideline-concordant therapies was 76.1%. Since guideline-recommended care is associated with better outcomes, this baselining finding highlights the need for appropriate treatment selection and intensification for mHSPC patients.

Methodological quality and clinical recommendations of guidelines on the management of dyslipidaemias for cardiovascular disease risk reduction: a systematic review and an appraisal through AGREE II and AGREE REX tools.

BACKGROUND: Clinical practice guidelines (CPGs) are statements to assist practitioners and stakeholders in decisions about healthcare. Low methodological quality guidelines may prejudice decision-making and negatively affect clinical outcomes in non-communicable diseases, such as cardiovascular diseases worsted by poor lipid management. We appraised the quality of CPGs on dyslipidemia management and synthesized the most updated pharmacological recommendations. METHODS: A systematic review following international recommendations was performed. Searches to retrieve CPG on pharmacological treatments in adults with dyslipidaemia were conducted in PubMed, Scopus, and Trip databases. Eligible articles were assessed using AGREE II (methodological quality) and AGREE-REX (recommendation excellence) tools. Descriptive statistics were used to summarize data. The most updated guidelines (published after 2019) had their recommendations qualitatively synthesized in an exploratory analysis. RESULTS: Overall, 66 guidelines authored by professional societies (75%) and targeting clinicians as primary users were selected. The AGREE II domains Scope and Purpose (89%) and Clarity of Presentation (97%), and the AGREE-REX item Clinical Applicability (77.0%) obtained the highest values. Conversely, guidelines were methodologically poorly performed/documented (46%) and scarcely provided data on the implementability of practical recommendations (38%). Recommendations on pharmacological treatments are overall similar, with slight differences concerning the use of supplements and the availability of drugs. CONCLUSION: High-quality dyslipidaemia CPG, especially outside North America and Europe, and strictly addressing evidence synthesis, appraisal, and recommendations are needed, especially to guide primary care decisions. CPG developers should consider stakeholders' values and preferences and adapt existing statements to individual populations and healthcare systems to ensure successful implementation interventions.