Additional file 1: of Effectiveness and patient safety of platelet aggregation inhibitors in the prevention of cardiovascular disease and ischemic stroke in older adults – a systematic review

Search string search 1 and 2. (DOCX 102 kb

Effectiveness and patient safety of platelet aggregation inhibitors in the prevention of cardiovascular disease and ischemic stroke in older adults - a systematic review

BACKGROUND: Platelet aggregation inhibitors (PAI) are among the most frequently prescribed drugs in older people, though evidence about risks and benefits of their use in older adults is scarce. The objectives of this systematic review are firstly to identify the risks and benefits of their use in the prevention and treatment of vascular events in older adults, and secondly to develop recommendations on discontinuing PAI in this population if risks outweigh benefits. METHODS: Staged systematic review consisting of three searches. Searches 1 and 2 identified systematic reviews and meta-analyses. Search 3 included controlled intervention and observational studies from review-articles not included in searches 1 and 2. All articles were assessed by two independent reviewers regarding the type of study, age of participants, type of intervention, and clinically relevant outcomes. After data extraction and quality appraisal we developed recommendations to stop the prescribing of specific drugs in older adults following the Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. RESULTS: Overall, 2385 records were screened leading to an inclusion of 35 articles reporting on 22 systematic reviews and meta-analyses, 11 randomised controlled trials, and two observational studies. Mean ages ranged from 57.0 to 84.6 years. Ten studies included a subgroup analysis by age. Overall, based on the evaluated evidence, three recommendations were formulated. First, the use of acetylsalicylic acid (ASA) for primary prevention of cardiovascular disease (CVD) in older people cannot be recommended due to an uncertainty in the risk-benefit ratio (weak recommendation; low quality of evidence). Secondly, the combination of ASA and clopidogrel in patients without specific indications should be avoided (strong recommendation; moderate quality of evidence). Lastly, to improve the effectiveness and reduce the risks of stroke prevention therapy in older people with atrial fibrillation (AF) and a CHA2DS2-VASc score of ≥ 2, the use of ASA for the primary prevention of stroke should be discontinued in preference for the use of oral anticoagulants (weak recommendation; low quality of evidence). CONCLUSIONS: The use of ASA for the primary prevention of CVD and the combination therapy of ASA and clopidogrel for the secondary prevention of vascular events in older people may not be justified. The use of oral anticoagulants instead of ASA in older people with atrial fibrillation may be recommended. Further high quality studies with older adults are neededThe PRIMA-eDS study was supported by a grant from the European Commission within the 7th Framework Programme (Grant No. 305388–2). The work of YVM was also supported by a grant from the NIHR Greater Manchester Primary Care Patient Safety Translational Research Centre. The publication charge was funded by the University of Witten/Herdeck

Acid-base physiology and CO2 homeostasis: Regulation and compensation in response to elevated environmental CO2

Acid-base balance is one of the most tightly regulated physiological processes. Accumulation of metabolic CO2 produced at the tissues causes extra- or intracellular acidosis that can disrupt cellular processes. Consequently, fish have a well-developed system for CO2 transport and excretion; however, the system varies significantly among fish groups, which we review in this chapter. Elevated environmental CO2 that occurs naturally or due to anthropogenic factors (e.g., climate change and in aquaculture), in both freshwater and seawater, induces a rapid acid-base disturbance in fish. The resulting acidosis is compensated by a net elevation in plasma in exchange for [Cl−], primarily through processes at the gills, but also the kidney. The rate and completeness of acid-base compensation during CO2 exposure is affected by water ion composition, and at high CO2 levels, there appears to be an upper limit to the increase in plasma . Fish that naturally live in such high CO2 environments appear to have an exceptional capacity for intracellular pH regulation. While it has long been thought that fish would not be affected by climate change relevant CO2 levels, negative physiological effects are seen. The effect of fluctuating CO2 levels in both marine and freshwater environments may be especially problematic, and an area where more research is required