Familial hypercholesterolaemia (FH) is a dominant and highly penetrant monogenic disorder present from birth that markedly elevates plasma low-density lipoprotein (LDL)-cholesterol concentration and, ...if untreated, leads to premature atherosclerosis and coronary artery disease (CAD). There are approximately 100,000 people with FH in Australia. However, an overwhelming majority of those affected remain undetected and inadequately treated, consistent with FH being a leading challenge for public health genomics. To further address the unmet need, we provide an updated guidance, presented as a series of systematically collated recommendations, on the care of patients and families with FH. These recommendations have been informed by an exponential growth in published works and new evidence over the last 5 years and are compatible with a contemporary global call to action on FH. Recommendations are given on the detection, diagnosis, assessment and management of FH in adults and children. Recommendations are also made on genetic testing and risk notification of biological relatives who should undergo cascade testing for FH. Guidance on management is based on the concepts of risk re-stratification, adherence to heart healthy lifestyles, treatment of non-cholesterol risk factors, and safe and appropriate use of LDL-cholesterol lowering therapies, including statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors and lipoprotein apheresis. Broad recommendations are also provided for the organisation and development of health care services. Recommendations on best practice need to be underpinned by good clinical judgment and shared decision making with patients and families. Models of care for FH need to be adapted to local and regional health care needs and available resources. A comprehensive and realistic implementation strategy, informed by further research, including assessments of cost-benefit, will be required to ensure that this new guidance benefits all Australian families with or at risk of FH.
Summary
Aims: The primary aim of this study was to describe the pharmacokinetics of total and unbound bupivacaine and ropivacaine following epidural bolus and infusion in neonates and young infants. ...Secondary aims were to investigate the influence of alpha‐1‐acid glycoprotein (AAG) on the concentration–time profiles and to determine the efficacy and adverse event profile of the epidural regimen.
Methods/Materials: Thirty‐one infants aged 40–63 weeks of postmenstrual age (PMA) undergoing hernia repair or abdominal surgery received an epidural injection of 1.5 mg·kg−1 bupivacaine (0.25%) or ropivacaine (0.2%) followed 2 h later by an infusion of 0.2 mg·kg−1·h−1 in those undergoing abdominal surgery. Total and unbound concentrations of bupivacaine and ropivacaine were analyzed using nonmem. Hourly pain scores and adverse effects were recorded.
Results: Bupivacaine data were available from 11 infants (five had infusions) and ropivacaine from 13 infants (four had infusions). Alpha‐1‐acid glycoprotein and total bupivacaine and ropivacaine concentrations accumulated during infusions, but unbound concentrations did not. Maximum unbound concentrations for bupivacaine and ropivacaine were 0.12 mg·l−1 (bupivacaine) and 0.13 mg·l−1 (ropivacaine). Typical clearance/bioavailability estimates of total (unbound) bupivacaine were 0.215 (4.65) l·h−1·kg−1 and of total (unbound) ropivacaine were 0.288 (3.31) l·h−1·kg−1. Pain scores requiring pain team referral occurred once with bupivacaine and four times with ropivacaine. No toxicity was observed.
Conclusions: Epidural infusions of 0.2 mg−1·kg−1·h−1 bupivacaine or ropivacaine appeared to be well tolerated and efficacious in this population. No accumulation of unbound drug concentrations occurred.
Climate change presents an emerging challenge to the sustainable management of tuna fisheries, and robust information is essential to ensure future sustainability. Climate and harvest affect tuna ...stocks, populations of non-target, dependent species and the ecosystem. To provide relevant advice we need an improved understanding of oceanic ecosystems and better data to parameterise the models that forecast the impacts of climate change. Currently ocean-wide data collection in the Pacific Ocean is primarily restricted to oceanographic data. However, the fisheries observer programs that operate in the region offer an opportunity to collect the additional information on the mid and upper trophic levels of the ecosystem that is necessary to complement this physical data, including time-series of distribution, abundance, size, composition and biological information on target and non-target species and mid trophic level organisms. These observer programs are in their infancy, with limited temporal and spatial distribution but recent international and national policy decisions have been made to expand their coverage. We identify a number of actions to initiate this monitoring including: consolidating collaborations to ensure the use of best quality data; developing consistency between sub-regional observer programmes to ensure that they meet the objectives of ecosystem monitoring; interrogating of existing time series to determine the most appropriate spatial template for monitoring; and exploring existing ecosystem models to identify suitable indicators of ecosystem status and change. The information obtained should improve capacity to develop fisheries management policies that are resilient and can be adapted to climate change.
Abstract Antiplatelet agents are a cornerstone of therapy for patients with atherosclerotic vascular disease. There is presently a lack of comprehensive guidelines focusing on the use of antiplatelet ...drugs in patients currently manifesting or at elevated risk of cardiovascular disease. The Canadian Antiplatelet Therapy Guidelines Committee reviewed existing disease-based guidelines and subsequently published literature and used expert opinion and review to develop guidelines on the use of antiplatelet therapy in the outpatient setting. This Executive Summary provides an abbreviated version of the principal recommendations. Antiplatelet therapy appears to be generally underused, perhaps in part because of a lack of clear, evidence-based guidance. Here, we provide specific guidelines for secondary prevention in patients discharged from hospital after acute coronary syndromes, percutaneous coronary intervention, or coronary artery bypass grafting; patients with a history of transient cerebral ischemic events or strokes; and patients with peripheral arterial disease. Issues related to primary prevention are also addressed, in addition to special clinical contexts such as diabetes, heart failure, chronic kidney disease, pregnancy or lactation, and perioperative management. Recommendations are provided regarding pharmacologic interactions that may occur during combination therapy with warfarin, clopidogrel, and proton-pump inhibitors, or aspirin and nonsteroidal anti-inflammatory drugs, as well as for the management of bleeding complications. The complete guidelines document is published as a supplementary issue of the Canadian Journal of Cardiology and is available at http://www.ccs.ca/.
This guide describes how to establish a notetaking program to benefit students with hearing impairments in mainstream settings. Chapter 1 discusses the need for notetakers and includes subjects such ...as providing equal access, high-tech and low-tech notetaking, how the notes can be used, and who can use the notes. Chapter 2 provides information on obtaining administrative support, working through resistance, identifying clientele, assessing needs, and making preliminary plans. Chapters 3 and 4 deal with getting started and recruiting notetakers, including qualifications for notetakers. Chapter 5 focuses on training students to use notes and reviews readiness strategies, the training of college students, establishment of policies and expectations, and communication about the program and policies. Chapter 6 discusses training topics and methods for a training program for notetakers. Chapter 7 provides sample training agendas for 1-day, three-session, and multi-session programs. Chapters 8 and 9 highlight the principles of notetaking and provide tips for supervisors. Chapter 10 discusses evaluation of notetaking and continuing professional development for notetakers. Appendices include job descriptions of notetaker supervisors and elementary/secondary notetakers, evaluation forms, and a summary of the Americans with Disabilities Act. (Contains 46 references.) (CR)
Osteoporotic fractures are widely recognized as a common and important cause of disability and death among postmenopausal women.
1
,
2
Osteoporosis is less common in men,
3
but approximately 25 to 30 ...percent of all hip fractures occur in men,
4
and many men have vertebral deformities.
5
The number of hip fractures among men and women is rising, and by 2025, the number of hip fractures occurring annually in men is expected to exceed 1.1 million worldwide — a figure that is close to the incidence of 1.2 million hip fractures among women in 1990.
4
The causes of osteoporosis in men include an . . .
One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood
.... Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain-gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials.
PDF
