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Background The Atrial fibrillation Better Care (ABC) pathway is the gold-standard approach to atrial fibrillation (AF) management, but the effect of implementation on health outcomes in care home residents is unknown. Objective To examine associations between ABC pathway adherence and stroke, transient ischaemic attack, cardiovascular hospitalisation, major bleeding, mortality and a composite of all these outcomes in care home residents. Methods A retrospective cohort study of older care home residents (≥65 years) in Wales with AF was conducted between 1 January 2003 and 31 December 2018 using the Secure Anonymised Information Linkage Databank. Adherence to the ABC pathway was assessed at care home entry using pre-specified definitions. Cox proportional hazard and competing risk models were used to estimate the risk of health outcomes according to ABC adherence. Results From 14,493 residents (median [interquartile range] age 87.0 [82.6–91.2] years, 35.2% male) with AF, 5,531 (38.2%) were ABC pathway adherent. Pathway adherence was not significantly associated with risk of the composite outcome (adjusted hazard ratio, 95% confidence interval [CI]: 1.01 [0.97–1.05]). There was a significant independent association observed between ABC pathway adherence and a reduced risk of myocardial infarction (0.70 [0.50–0.98]), but a higher risk of haemorrhagic stroke (1.59 [1.06–2.39]). ABC pathway adherence was not significantly associated with any other individual health outcomes examined. Conclusion An ABC adherent approach in care home residents was not consistently associated with improved health outcomes. Findings should be interpreted with caution owing to difficulties in defining pathway adherence using routinely collected data and an individualised approach is recommended. [ABSTRACT FROM AUTHOR]

Oral anticoagulants (OACs) are the cornerstone of stroke prevention in atrial fibrillation (AF), but prescribing decisions in older people are complicated. Clinicians must assess the net clinical benefit of OAC in the context of multiple chronic conditions, polypharmacy, frailty and life expectancy. The under-representation of high-risk, older adult sub-populations in clinical trials presents the challenge of choosing the right OAC, where a 'one-size-fits-all' approach cannot be taken. This review discusses OAC approaches for stroke prevention in older people with AF and presents a prescribing aid to support clinicians' decision-making. High-risk older adults with multiple chronic conditions, specifically chronic kidney disease, dementia/cognitive impairment, previous stroke/transient ischemic attack or intracranial hemorrhage, polypharmacy, frailty, low body weight, high falls risk, and those aged ≥75 years are considered. Non-vitamin K antagonist OACs are the preferred first-line OAC in older adults with AF, including high-risk subpopulations, after individual assessment of stroke and bleeding risk, except those with mechanical heart valves and moderate-to-severe mitral stenosis. Head-to-head comparisons of NOACs are not available, therefore the choice of drug (and dose) should be based on an individual's risk (stroke and bleeding) and incorporate their treatment preferences. Treatment decisions must be person-centered and principles of shared decision-making applied. [ABSTRACT FROM AUTHOR]

Introduction: Oxidative stress is one of many factors suspected to promote antinuclear autoantibody (ANA) formation. Reactive oxygen species can induce changes in the antigenic structure of macromolecules, causing the immune system to treat them as "neo-antigens" and start production of autoantibodies. This study was designed to evaluate the relationship between oxidative stress markers, lifestyle factors and the detection of ANA. Material and methods: We examined measures of oxidative stress indices of free-radical damage to lipids and proteins, such as total oxidant status (TOS), concentration of protein thiol groups (PSH), and malondialdehyde (MDA), activity of superoxide dismutase (SOD) in 1731 serum samples. The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid (UA) concentration, were also measured and the oxidative stress index (OSI-index) was calculated. All samples were tested for the presence of ANA using an indirect immunofluorescence assay (IIFA). Results: The presence of ANA in women was associated with lower physical activity (p = 0.036), less frequent smoking (p = 0.007) and drinking of alcohol (p = 0.024) accompanied by significant changes in SOD isoenzymes activity (p < 0.001) and a higher uric acid (UA) concentration (p < 0.001). In ANA positive males we observed lower concentrations of PSH (p = 0.046) and increased concentrations of MDA (p = 0.047). Conclusions: The results indicate that local oxidative stress may be associated with increased probability of ANA formation in a sex-specific manner. [ABSTRACT FROM AUTHOR]

Muscle wasting is one of the main causes for exercise intolerance and ventilatory inefficiency in patients with heart failure and a strong predictor of frailty and reduced survival. The prevalence of sarcopenia is at least 20% in patients with heart failure. Patients with heart failure often have subclinical systemic inflammation, which may exert sustained effects on skeletal muscle. Besides exercise, nutrition should also be carefully evaluated as an appropriate diet with selected nutraceuticals may be able to stimulate muscle anabolism and inhibit muscle catabolism. This review summarizes the epidemiological and clinical trial evidence supporting the recommendations for the use of nutraceuticals with anti-inflammatory properties in heart failure and provides an overview of the state of the evidence for nutraceutical supplementation to prevent and/or mitigate heart failure muscle wasting. [ABSTRACT FROM AUTHOR]

Background: Treatment decisions about oral anticoagulants (OACs) for atrial fibrillation (AF) are complex in older care home residents. Aim: To explore factors associated with OAC prescription. Design and setting: Retrospective cohort study set in care homes in Wales, UK, listed in the Care Inspectorate Wales Registry 2017/18. Method: Analysis of anonymised individual-level electronic health and administrative data was carried out on people aged ≥65 years entering a care home between 1 January 2003 and 31 December 2018, provisioned from the Secure Anonymised Information Linkage Databank. Results: Between 2003 and 2018, 14 493 people with AF aged ≥65 years became new residents in care homes in Wales and 7057 (48.7%) were prescribed OACs (32.7% in 2003 compared with 72.7% in 2018) within 6 months before care home entry. Increasing age and prescription of antiplatelet therapy were associated with lower odds of OAC prescription (adjusted odds ratio [aOR] 0.96 per 1-year age increase, 95% confidence interval [CI] = 0.95 to 0.96 and aOR 0.91, 95% CI = 0.84 to 0.98, respectively). Conversely, prior venous thromboembolism (aOR 4.06, 95% CI = 3.17 to 5.20), advancing frailty (mild: aOR 4.61, 95% CI = 3.95 to 5.38; moderate: aOR 6.69, 95% CI = 5.74 to 7.80; and severe: aOR 8.42, 95% CI = 7.16 to 9.90), and year of care home entry from 2011 onwards (aOR 1.91, 95% CI = 1.76 to 2.06) were associated with higher odds of an OAC prescription. Conclusion: There has been an increase in OAC prescribing in older people newly admitted to care homes with AF. This study provides an insight into the factors influencing OAC prescribing in this population. [ABSTRACT FROM AUTHOR]

Solid oral dosage forms (SODFs) (often called pills by patients) are the default formulation to treat medical ailments. Beneficial therapeutic outcomes rely on patients taking them as directed. Up to 40% of the population experience difficulties swallowing SODFs, resulting in reduced adherence and impaired therapeutic efficacy. Often associated with children, this also presents in adults with dysphagia, and without any organic dysphagia (non‐physiological‐related or functional dysphagia). This review aims to identify and appraise current interventions used to screen for and overcome pill aversion in adults with functional dysphagia. A comprehensive search of the literature was conducted. Articles reporting pill aversion in adults aged ≥18 years with no underlying cause, history of, or existing dysphagia were included. Study quality was determined using the STROBE tool for observational studies. A narrative synthesis of the findings was prepared. We identified 18 relevant cohort studies, which demonstrate that pill aversion is a global problem. Perceived ease of and/or SODF swallowability appears to be influenced by female gender, younger age, co‐morbidities (e.g., depression), and physical SODF properties. Patients often modify their medicines rather than raise this issue with their healthcare team. Screening for pill aversion is haphazard but controlled postural adjustments, coating SODFs and behavioural interventions appear to be successful solutions. SODF swallowing difficulties are a barrier to effective medication use. Healthcare professionals must recognise that pill aversion is a problem requiring identification through effective screening and resolution by training interventions, appropriate formulation selection or specialist referral. [ABSTRACT FROM AUTHOR]

Objective To determine atrial fibrillation (AF) prevalence and temporal trends, and examine associations between AF and risk of adverse health outcomes in older care home residents. Methods Retrospective cohort study using anonymised linked data from the Secure Anonymised Information Linkage Databank on CARE home residents in Wales with AF (SAIL CARE-AF) between 2003 and 2018. Fine-Gray competing risk models were used to estimate the risk of health outcomes with mortality as a competing risk. Cox regression analyses were used to estimate the risk of mortality. Results There were 86,602 older care home residents (median age 86.0 years [interquartile range 80.8–90.6]) who entered a care home between 2003 and 2018. When the pre-care home entry data extraction was standardised , the overall prevalence of AF was 17.4% (95% confidence interval 17.1–17.8) between 2010 and 2018. There was no significant change in the age- and sex-standardised prevalence of AF from 16.8% (15.9–17.9) in 2010 to 17.0% (16.1–18.0) in 2018. Residents with AF had a significantly higher risk of cardiovascular mortality (adjusted hazard ratio [HR] 1.27 [1.17–1.37], P  < 0.001), all-cause mortality (adjusted HR 1.14 [1.11–1.17], P  < 0.001), ischaemic stroke (adjusted sub-distribution HR 1.55 [1.36–1.76], P  < 0.001) and cardiovascular hospitalisation (adjusted sub-distribution HR 1.28 [1.22–1.34], P  < 0.001). Conclusions Older care home residents with AF have an increased risk of adverse health outcomes, even when higher mortality rates and other confounders are accounted for. This re-iterates the need for appropriate oral anticoagulant prescription and optimal management of cardiovascular co-morbidities, irrespective of frailty status and predicted life expectancy. [ABSTRACT FROM AUTHOR]

Dyslipidemia in patients with type 2 diabetes (DMT2) is one of the worst controlled worldwide, with only about 1/4 of patients being on the low-density lipoprotein cholesterol (LDL-C) target. There are many reasons of this, including physicians' inertia, including diabetologists and cardiologists, therapy nonadherence, but also underusage and underdosing of lipid lowering drugs due to unsuitable cardiovascular (CV) risk stratification. In the last several years there is a big debate on the risk stratification of DMT2 patients, with the strong indications that all patients with diabetes should be at least at high cardiovascular disease (CVD) risk. Moreover, we have finally lipid lowering drugs, that not only allow for the effective reduction of LDL-C and do not increase the risk of new onset diabetes (NOD), and/or glucose impairment; in the opposite, some of them might effectively improve glucose control. One of the most interesting is pitavastatin, which is now available in Europe, with the best metabolic profile within statins (no risk of NOD, improvement of fasting blood glucose, HOMA-IR, HbA1c), bempedoic acid (with the potential for the reduction of NOD risk), innovative therapies—PCSK9 inhibitors and inclisiran with no DMT2 risk increase, and new forthcoming therapies, including apabetalone and obicetrapib—for the latter one with the possibility of even decreasing the number of patients diagnosed with prediabetes and DMT2. Altogether, nowadays we have possibility to individualize lipid lowering therapy in DMT2 patients and increase the number of patients on LDL-C goal without any risk of new onset diabetes and/or diabetes control worsening, and in consequence to reduce the risk of CVD complications due to progression of atherosclerosis in this patients' group. [ABSTRACT FROM AUTHOR]

Aims Statin intolerance (SI) represents a significant public health problem for which precise estimates of prevalence are needed. Statin intolerance remains an important clinical challenge, and it is associated with an increased risk of cardiovascular events. This meta-analysis estimates the overall prevalence of SI, the prevalence according to different diagnostic criteria and in different disease settings, and identifies possible risk factors/conditions that might increase the risk of SI. Methods and results We searched several databases up to 31 May 2021, for studies that reported the prevalence of SI. The primary endpoint was overall prevalence and prevalence according to a range of diagnostic criteria [National Lipid Association (NLA), International Lipid Expert Panel (ILEP), and European Atherosclerosis Society (EAS)] and in different disease settings. The secondary endpoint was to identify possible risk factors for SI. A random-effects model was applied to estimate the overall pooled prevalence. A total of 176 studies [112 randomized controlled trials (RCTs); 64 cohort studies] with 4 143 517 patients were ultimately included in the analysis. The overall prevalence of SI was 9.1% (95% confidence interval 8.0–10%). The prevalence was similar when defined using NLA, ILEP, and EAS criteria [7.0% (6.0–8.0%), 6.7% (5.0–8.0%), 5.9% (4.0–7.0%), respectively]. The prevalence of SI in RCTs was significantly lower compared with cohort studies [4.9% (4.0–6.0%) vs. 17% (14–19%)]. The prevalence of SI in studies including both primary and secondary prevention patients was much higher than when primary or secondary prevention patients were analysed separately [18% (14–21%), 8.2% (6.0–10%), 9.1% (6.0–11%), respectively]. Statin lipid solubility did not affect the prevalence of SI [4.0% (2.0–5.0%) vs. 5.0% (4.0–6.0%)]. Age [odds ratio (OR) 1.33, P  = 0.04], female gender (OR 1.47, P  = 0.007), Asian and Black race (P  < 0.05 for both), obesity (OR 1.30, P  = 0.02), diabetes mellitus (OR 1.26, P  = 0.02), hypothyroidism (OR 1.37, P  = 0.01), chronic liver, and renal failure (P  < 0.05 for both) were significantly associated with SI in the meta-regression model. Antiarrhythmic agents, calcium channel blockers, alcohol use, and increased statin dose were also associated with a higher risk of SI. Conclusion Based on the present analysis of >4 million patients, the prevalence of SI is low when diagnosed according to international definitions. These results support the concept that the prevalence of complete SI might often be overestimated and highlight the need for the careful assessment of patients with potential symptoms related to SI. [ABSTRACT FROM AUTHOR]

Aims: Inflammation plays a central role in the pathogenesis and clinical manifestations of atherosclerosis. Randomized controlled trials have investigated the potential benefit of colchicine in reducing cardiovascular (CV) events in patients with coronary artery disease (CAD) but produced conflicting results. The aim of this meta‐analysis was to evaluate the efficacy and safety of colchicine in patients with CAD. Methods: We systematically searched selected electronic databases from inception until 10 December 2020. Primary clinical endpoints were: major adverse cardiac events; all‐cause mortality; CV mortality; recurrent myocardial infarction; stroke; hospitalization; and adverse medication effects. Secondary endpoints were short‐term effect of colchicine on inflammatory markers. Results: Twelve randomized controlled trials with a total of 13 073 patients with CAD (colchicine n = 6351 and placebo n = 6722) were included in the meta‐analysis. At mean follow‐up of 22.5 months, the colchicine group had lower risk of major adverse cardiac events (6.20 vs. 8.87%; P <.001), recurrent myocardial infarction (3.41 vs. 4.41%; P =.005), stroke (0.40 vs. 0.90%; P =.002) and hospitalization due to CV events (0.90 vs. 2.87%; P =.02) compared to the control group. The 2 patient groups had similar risk for all‐cause mortality (2.08 vs. 1.88%; P =.82) and CV mortality (0.71 vs. 1.01%; P =.38). Colchicine significantly reduced high‐sensitivity C‐reactive protein (−4.25, P =.001) compared to controls but did not significantly affect interleukin (IL)‐β1 and IL‐18 levels. Conclusion: Colchicine reduced CV events and inflammatory markers, high‐sensitivity C‐reactive protein and IL‐6, in patients with coronary disease compared to controls. Its impact on cardiovascular and all‐cause mortality requires further investigation. [ABSTRACT FROM AUTHOR]

Aims: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a key risk factor for ischaemic stroke. Following AF detection, treatment with oral anticoagulation can significantly lower mortality and morbidity rates associated with this risk. The availability of several hand-held devices which can detect AF may enable trained health professionals to adopt AF screening approaches which do not interfere with people's daily routines. This study aims to investigate the effectiveness of a hand-held device (the MyDiagnostick single-lead Electrocardiogram (ECG) sensor) in screening for AF when embedded into the handles of supermarket trolleys. Methods: A mixed methods two-phase approach will be taken. The quantitative first phase will involve the recruitment of 2000 participants from a convenience sample at four large supermarkets with pharmacies. Prospective participants will be asked to conduct their shopping using a trolley embedded with a MyDiagnostick sensor. If the device identifies a participant with AF, the in-store pharmacist will be dispatched to take a manual pulse measurement and a static control sensor reading and offer a cardiologist consultation referral. When the sensor does not detect AF, a researcher will confirm the reading with a manual pulse measurement. ECGs will be compiled, and the sensitivity, specificity and positive and negative predictive values will be determined. A qualitative second phase will consist of semi-structured interviews carried out with those pharmacists and store managers in-store during the running of the trial period. These will explore the perceptions of staff regarding the merits of embedding sensors in the handles of supermarket trolleys to detect AF. Conclusion: This feasibility study will inform a larger future definitive trial. [ABSTRACT FROM AUTHOR]

*Based on the available data the risk of statin-associated muscle symptoms with pitavastatin is similar to placebo [3]; #with low-to moderate intensity statin therapy; $ moderate intensity statin therapy for partial statin intolerance patients; **preferably with ezetimibe. We can consider four different scenarios when a patient presents with adverse effects that they perceive to be due to statin therapy, each requiring a different approach: (i) The adverse effect may be entirely unrelated to statin therapy. This enables the treatment regimen to be matched to the patients' needs at the outset, potentially commencing therapy with more than one drug, rather than starting the patient on a single drug, which could not conceivably enable them to reach treatment targets. [Extracted from the article]

Background: The anti-DFS70 autoantibodies are one of the most commonly and widely described agent of unknown clinical significance, frequently detected in healthy individuals. It is not known whether the DFS70 autoantibodies are protective or pathogenic. One of the factors suspected of inducing the formation of anti-DFS70 antibodies is increased oxidative stress. We evaluated the coexistence of anti-DFS70 antibodies with selected markers of oxidative stress and investigated whether these antibodies could be considered as indirect markers of oxidative stress. Methods: The intensity of oxidative stress was measured in all samples via indices of free-radical damage to lipids and proteins such as total oxidant status (TOS), concentrations of lipid hydroperoxides (LPH), lipofuscin (LPS), and malondialdehyde (MDA). The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid concentration (UA), were also measured, as well as the activity of superoxide dismutase (SOD). Based on TOS and TAS values, the oxidative stress index (OSI) was calculated. All samples were also tested with indirect immunofluorescence assay (IFA) and 357 samples were selected for direct monospecific anti DFS70 enzyme-linked immunosorbent assay (ELISA) testing. Results: The anti-DFS70 antibodies were confirmed by ELISA test in 21.29% of samples. Compared with anti-DFS70 negative samples we observed 23% lower concentration of LPH (P =.038) and 11% lower concentration of UA (P =.005). TOS was 20% lower (P =.014). The activity of SOD was up to 5% higher (P =.037). The Pearson correlation showed weak negative correlation for LPH, UA, and TOS and a weak positive correlation for SOD activity. Conclusion: In samples positive for the anti-DFS70 antibody a decreased level of oxidative stress was observed, especially in the case of samples with a high antibody titer. Anti-DFS70 antibodies can be considered as an indirect marker of reduced oxidative stress or a marker indicating the recent intensification of antioxidant processes. [ABSTRACT FROM AUTHOR]

Purpose of Review: Remarkable reductions in cardiovascular morbidity and mortality have been achieved in recent decades through the widespread use of 'small-molecule' hypolipidaemic drugs such as statins and ezetimibe. An alternative approach is to perturb the production of proteins through ribonucleic acid (RNA) silencing, leading to long-lasting knock-down of specific biological molecules. This review describes the scientific basis of RNA silencing, and critically evaluates the evidence relating to inclisiran, a small interfering RNA against proprotein convertase subtilisin kexin 9 (PCSK9). Recent Findings: Pooled analysis of three recent ORION trials has demonstrated that twice-yearly administration of inclisiran reduces LDL-C by 50% in a range of patient groups, with only mild adverse effects. Summary: Inclisiran provides safe, effective and long-lasting reductions in PCSK9 and LDL-C. The results of the phase-3 ORION-4 outcomes study are eagerly awaited. Further promising RNA silencing technologies have the potential to improve the management of dyslipidaemia. [ABSTRACT FROM AUTHOR]

Introduction: Pyroptosis is a regulated form of cell death, which is often a consequence of the activation of inflammatory caspases.Methods: Appropriate inflammatory responses and the induction of pyroptosis enhance the clearance of pathogens and increase innate immunity.Results: However, excessive pyroptosis contributes to a hyperinflammatory response and aggravates tissue damage, thereby causing inflammatory diseases. There have been recent reports on the modulation of pyroptosis by statins, which may explain part of the pleiotropic actions of these drugs in inflammatory diseases and cancer.Conclusions: Herein, the extant evidence for the potential value of statins in targeting pyroptosis in various diseases is reviewed. [ABSTRACT FROM AUTHOR]

Inflammation is a marker of arterial disease stemming from cholesterol-dependent to -independent molecular mechanisms. In recent years, the role of inflammation in atherogenesis has been underpinned by pharmacological approaches targeting systemic inflammation that have led to a significant reduction in cardiovascular disease (CVD) risk. Although the use of nutraceuticals to prevent CVD has largely focused on lipid-lowering (e.g, red-yeast rice and omega-3 fatty acids), there is growing interest and need, especially now in the time of coronavirus pandemic, in the use of nutraceuticals to reduce inflammatory markers, and potentially the inflammatory CVD burden, however, there is still not enough evidence to confirm this. Indeed, diet is an important lifestyle determinant of health and can influence both systemic and vascular inflammation, to varying extents, according to the individual nutraceutical constituents. Thus, the aim of this Position Paper is to provide the first attempt at recommendations on the use of nutraceuticals with effective anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

Myocarditis refers to the clinical and histological characteristics of a diverse range of inflammatory cellular pathophysiological conditions which result in cardiac dysfunction. Myocarditis is a major cause of mortality in individuals less than 40 years of age and accounts for approximately 20% of cardiovascular disease (CVD) events. Myocarditis contributes to dilated cardiomyopathy in 30% of patients and can progress to cardiac arrest, which has a poor prognosis of <40% survival over 10 years. Myocarditis has also been documented after infection with SARS-CoV-2. The most commonly used lipid-lowering therapies, HMG-CoA reductase inhibitors (statins), decrease CVD-related morbidity and mortality. In addition to their lipid-lowering effects, increasing evidence supports the existence of several additional beneficial, 'pleiotropic' effects of statins. Recently, several studies have indicated that statins may attenuate myocarditis. Statins modify the lipid oxidation, inflammation, immunomodulation, and endothelial activity of the pathophysiology and have been recommended as adjuvant treatment. In this review, we focus on the mechanisms of action of statins and their effects on myocarditis, SARS-CoV-2 and CVD. [ABSTRACT FROM AUTHOR]

There is a strong evidence that more marked lowering of low-density lipoprotein cholesterol (LDL-C) leads to progressively lower risk of cardiovascular disease (CVD) events. The evidence on validity of this hypothesis comes from epidemiological, genetic and clinical studies. The hypothesis "the lower the better" has been recently strongly supported by the results of secondary prevention trials with PCSK9 inhibitors. The combination of PCSK9 inhibitors and statins has resulted in achieving extremely low LDL-C levels with additional reduction of CVD events in secondary prevention. However, despite large clinical benefits, the safety of aggressive LDL-C lowering should be always taken into consideration, and there is still an ongoing discussion on whether very low LDL-C might result in some non-CVD adverse events. However, based on the available knowledge, so far the serious adverse events associated with achieving of very low LDL-C levels or intensive drug therapy have not been noted. These positive clinical effects were reflected in current ESC/EAS Guidelines (2019) for dyslipidaemia management. The experts strongly recommended the LDL-C lowering to levels that have been achieved in trials of PCSK9 inhibitors. In this state of the art review, we aimed to finally justify the critical need for LDL-C reduction to very low levels in secondary prevention patients in order to be as low as possible, as early as possible, and preferably lifelong. [ABSTRACT FROM AUTHOR]

Introduction: In the absence of a European standardized postmarketing food supplement surveillance system (nutrivigilance), some member states and companies have developed their own approaches to monitoring potential adverse reactions to secure a high level of product safety. This paper describes the use of a nutrivigilance system in monitoring the incidence of spontaneously reported suspected adverse reactions associated with food supplements containing red yeast rice (RYR).Material and Methods: We report the data from a widely used product marketed under the trademark Armolipid/Armolipid Plus. Postmarketing information was collected in a voluntary nutrivigilance system established by the manufacturing company (Meda Pharma SpA, a Viatris Company, Monza, Italy). From 1st October 2004 to 31st December 2019, this system captured cases of suspected adverse reactions spontaneously reported by consumers, healthcare professionals, health authorities, regardless of causality.Results: The total number of case reports received mentioning the RYR food supplement product line was 542, in which 855 adverse events (AEs) were reported. The total reporting rate of AEs was estimated to be 0.037% of 2,287,449 exposed consumers. Of the 542 cases, 21 (0.0009% of exposed consumers) included suspected serious adverse events (SAEs). After careful investigation, 6 cases (0.0003% of consumers exposed) and 6 AEs were assessed by the manufacturer as serious and potentially related to exposure to the above-mentioned RYR-based nutraceutical.Conclusions: This nutrivigilance-derived data analysis clearly demonstrates a low prevalence of suspected adverse events associated with the red yeast rice product line. Consumer safety of food supplements could be generally improved by raising awareness of the importance of following the indications and warnings detailed in a food supplement's labeling. [ABSTRACT FROM AUTHOR]

Purpose of Review: Recent studies have demonstrated an important role for inflammation in the pathogenesis of atherosclerotic cardiovascular disease. Several studies have investigated the efficacy of colchicine (a widely used and safe anti-inflammatory drug) in patients with atherosclerosis. This review explains the rationale for the use of colchicine in this setting and critically appraises recent outcome trials. Recent Findings: Two large randomised-controlled trials LoDoCo2 (included patients with chronic coronary syndromes) and COLCOT (acute coronary syndromes) have demonstrated reductions in atherosclerotic cardiovascular events, but not mortality. A smaller study (COPS) found no beneficial effect of colchicine but was probably underpowered. Summary: Colchicine is effective at reducing cardiovascular events in chronic and acute coronary syndromes, although reductions in all-cause mortality have not been demonstrated during the period of follow-up in trials to date. Mild gastrointestinal symptoms are the most commonly reported adverse effects, although in well-designed randomised controlled trials these are relatively uncommon. [ABSTRACT FROM AUTHOR]

The very high-risk category includes both patients without documented CVD but with a very high probability of a cardiovascular event due to existing risk factors, as well as patients with previously diagnosed CVD and/or patients who have had a cardiovascular event.[1] The latter group of patients is also very heterogeneous, as it includes patients with various comorbidities and varying degrees of CVD progression, which are not mentioned in the risk categories. Furthermore, we strongly believe, based on EBM, that broadening the population of patients in whom LDL-C should be lowered so much will positively influence the effectiveness of therapy and consequently improve the prognosis in this most burdened group of patients. Cardiovascular disease (CVD) remains the most common cause of death worldwide.[1] Low-density lipoprotein cholesterol (LDL-C) is the most important risk factor for atherosclerosis and plays a significant role in the development of atherosclerotic CVD (ASCVD). [Extracted from the article]

Keywords: Therapeutic drug monitoring; precision dosing; personalized medicine; efficacy; toxicity; safety EN Therapeutic drug monitoring precision dosing personalized medicine efficacy toxicity safety 685 686 2 08/08/23 20230801 NES 230801 I 'What is there that is not poison? This can be achieved through therapeutic drug monitoring (TDM) I 'a multi-disciplinary clinical specialty aimed at improving patient care by individually adjusting the dose of drugs for which clinical experience or clinical trials have shown it improved outcome in the general or special populations' i [[2]]. Therapeutic drug monitoring of carbapenem antibiotics in critically ill patients: an overview of principles, recommended dosing regimens, and clinical outcomes. [Extracted from the article]

Associations between dietary fats and mortality are unclear. We evaluated the relationship between quartiles of total fat, mono-unsaturated (MUFA), polyunsaturated (PUFA) and saturated fatty acid (SFA) consumption, and all-cause, coronary heart disease (CHD), stroke, and type 2 diabetes (T2D)-associated mortality in 24,144 participants from the National Health and Nutrition Examination Surveys (NHANES) 1999–2010. We added our results to a meta-analysis based on searches until November 2018. In fully adjusted Cox-proportional hazard models in our prospective study, there was an inverse association between total fat (HR: 0.90, 95% confidence interval 0.82, 0.99, Q4 vs Q1) and PUFA (0.81, 0.78–0.84) consumption and all-cause mortality, whereas SFA were associated with the increased mortality (1.08, 1.04–1.11). In the meta-analysis of 29 prospective cohorts (n = 1,164,029) we found a significant inverse association between total fat (0.89, 0.82–0.97), MUFA (0.94, 0.89–0.99) and PUFA (0.89, 0.84–0.94) consumption and all-cause mortality. No association was observed between total fat and CVD (0.93, 0.80–1.08) or CHD mortality (1.03 0.99–1.09). A significant association between SFA intake and CHD mortality (1.10, 1.01–1.21) was observed. Neither MUFA nor PUFA were associated with CVD or CHD mortality. Inverse associations were observed between MUFA (0.80, 0.67–0.96) and PUFA (0.84, 0.80–0.90) intakes and stroke mortality. We showed differential associations of total fat, MUFA and PUFA with all-cause mortality, but not CVD or CHD mortalities. SFA was associated with higher all-cause mortality in NHANES and with CHD mortality in our meta-analysis. The type of fat intake appears to be associated with important health outcomes. [ABSTRACT FROM AUTHOR]