Efficacy and safety of colchicine in patients with coronary artery disease: a systematic review and meta-analysis of randomized controlled trials

Background: Inflammation plays a central role in the pathogenesis and clinical manifestations of atherosclerosis. Randomized controlled trials (RCTs) have investigated the potential benefit of colchicine in reducing cardiovascular events (CE) 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 10th December 2020. Primary clinical endpoints were: major adverse cardiac events (MACE), allcause mortality, cardio-vascular (CV) mortality, recurrent myocardial infarction (MI), stroke, hospitalization and adverse medication effects. Secondary endpoints were short-term effect of colchicine on inflammatory markers. Results: Twelve RCTs 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 MACE (6.20% vs. 8.87%; p<0.001), recurrent MI (3.41% vs. 4.41%; p=0.005), stroke (0.40% vs. 0.90%; p=0.002) and hospitalization due to CE (0.90% vs. 2.87%; p=0.02) compared to the control group. The two patient groups had similar risk for all-cause mortality (2.08% vs. 1.88%; p=0.82) and CV mortality (0.71% vs. 1.01%; p=0.38). Colchicine significantly reduced hs-CRP (-4.25, p=0.001) compared to controls but did not significantly affect IL-β1 and IL-18 levels. Conclusions: Colchicine reduced cardiovascular events and inflammatory markers, hs-CRP and IL-6, in patients with coronary disease compared to controls. Its impact on cardiovascular and all-cause mortality requires further investigation

The Association Between Daily Step Count and All-Cause and Cardiovascular Mortality: A Meta-Analysis

Aims There is good evidence showing that inactivity and walking minimal steps/day increase the risk of cardiovascular (CV) disease and general ill-health. The optimal number of steps and their role in health is, however, still unclear. Therefore, in this meta-analysis, we aimed to evaluate the relationship between step count and all-cause mortality and CV mortality.Methods and results We systematically searched relevant electronic databases from inception until 12 June 2022. The main endpoints were all-cause mortality and CV mortality. An inverse-variance weighted random-effects model was used to calculate the number of steps/day and mortality. Seventeen cohort studies with a total of 226 889 participants (generally healthy or patients at CV risk) with a median follow-up 7.1 years were included in the meta-analysis. A 1000-step increment was associated with a 15% decreased risk of all-cause mortality [hazard ratio (HR) 0.85; 95% confidence interval (CI) 0.81–0.91; P < 0.001], while a 500-step increment was associated with a 7% decrease in CV mortality (HR 0.93; 95% CI 0.91–0.95; P < 0.001). Compared with the reference quartile with median steps/day 3867 (2500–6675), the Quartile 1 (Q1, median steps: 5537), Quartile 2 (Q2, median steps 7370), and Quartile 3 (Q3, median steps 11 529) were associated with lower risk for all-cause mortality (48, 55, and 67%, respectively; P < 0.05, for all). Similarly, compared with the lowest quartile of steps/day used as reference [median steps 2337, interquartile range 1596–4000), higher quartiles of steps/day (Q1 = 3982, Q2 = 6661, and Q3 = 10 413) were linearly associated with a reduced risk of CV mortality (16, 49, and 77%; P < 0.05, for all). Using a restricted cubic splines model, we observed a nonlinear dose–response association between step count and all-cause and CV mortality (Pnonlineraly < 0.001, for both) with a progressively lower risk of mortality with an increased step count.Conclusion This meta-analysis demonstrates a significant inverse association between daily step count and all-cause mortality and CV mortality with more the better over the cut-off point of 3867 steps/day for all-cause mortality and only 2337 steps for CV mortality

Nutraceutical approaches to non-alcoholic fatty liver disease (NAFLD): A position paper from the International Lipid Expert Panel (ILEP)

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10–25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease. The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety

Step‐by‐step diagnosis and management of the nocebo/drucebo effect in statin‐associated muscle symptoms patients: a position paper from the International Lipid Expert Panel (ILEP)

Statin intolerance is a clinical syndrome whereby adverse effects (AEs) associated with statin therapy [most commonly statin-associated muscle symptoms (SAMS)] result in the discontinuation of therapy and consequently increase the risk of adverse cardiovascular outcomes. However, complete statin intolerance occurs in only a small minority of treated patients (estimated prevalence of only 3–5%). Many perceived AEs are misattributed (e.g. physical musculoskeletal injury and inflammatory myopathies), and subjective symptoms occur as a result of the fact that patients expect them to do so when taking medicines (the nocebo/drucebo effect)—what might be truth even for over 50% of all patients with muscle weakness/pain. Clear guidance is necessary to enable the optimal management of plasma in real-world clinical practice in patients who experience subjective AEs. In this Position Paper of the International Lipid Expert Panel (ILEP), we present a step-by-step patient-centred approach to the identification and management of SAMS with a particular focus on strategies to prevent and manage the nocebo/drucebo effect and to improve long-term compliance with lipid-lowering therapy

Evaluation of trauma care using TRISS method: the role of adjusted misclassification rate and adjusted w-statistic

<p>Abstract</p> <p>Background</p> <p>Major trauma is a leading cause of death worldwide. Evaluation of trauma care using Trauma Injury and Injury Severity Score (TRISS) method is focused in trauma outcome (deaths and survivors). For testing TRISS method TRISS misclassification rate is used. Calculating w-statistic, as a difference between observed and TRISS expected survivors, we compare our trauma care results with the TRISS standard.</p> <p>Aim</p> <p>The aim of this study is to analyze interaction between misclassification rate and w-statistic and to adjust these parameters to be closer to the truth.</p> <p>Materials and methods</p> <p>Analysis of components of TRISS misclassification rate and w-statistic and actual trauma outcome.</p> <p>Results</p> <p>The component of false negative (FN) (by TRISS method unexpected deaths) has two parts: preventable (Pd) and non-preventable (nonPd) trauma deaths. Pd represents inappropriate trauma care of an institution; otherwise nonpreventable trauma deaths represents errors in TRISS method. Removing patients with preventable trauma deaths we get an Adjusted misclassification rate: (FP + FN - Pd)/N or (b+c-Pd)/N. Substracting nonPd from FN value in w-statistic formula we get an Adjusted w-statistic: [FP-(FN - nonPd)]/N, respectively (FP-Pd)/N, or (b-Pd)/N).</p> <p>Conclusion</p> <p>Because adjusted formulas clean method from inappropriate trauma care, and clean trauma care from the methods error, TRISS adjusted misclassification rate and adjusted w-statistic gives more realistic results and may be used in researches of trauma outcome.</p

The impact of type of dietary protein, animal versus vegetable, in modifying cardiometabolic risk factors: A position paper from the International Lipid Expert Panel (ILEP).

Proteins play a crucial role in metabolism, in maintaining fluid and acid-base balance and antibody synthesis. Dietary proteins are important nutrients and are classified into: 1) animal proteins (meat, fish, poultry, eggs and dairy), and, 2) plant proteins (legumes, nuts and soy). Dietary modification is one of the most important lifestyle changes that has been shown to significantly decrease the risk of cardiovascular (CV) disease (CVD) by attenuating related risk factors. The CVD burden is reduced by optimum diet through replacement of unprocessed meat with low saturated fat, animal proteins and plant proteins. In view of the available evidence, it has become acceptable to emphasize the role of optimum nutrition to maintain arterial and CV health. Such healthy diets are thought to increase satiety, facilitate weight loss, and improve CV risk. Different studies have compared the benefits of omnivorous and vegetarian diets. Animal protein related risk has been suggested to be greater with red or processed meat over and above poultry, fish and nuts, which carry a lower risk for CVD. In contrast, others have shown no association of red meat intake with CVD. The aim of this expert opinion recommendation was to elucidate the different impact of animal vs vegetable protein on modifying cardiometabolic risk factors. Many observational and interventional studies confirmed that increasing protein intake, especially plant-based proteins and certain animal-based proteins (poultry, fish, unprocessed red meat low in saturated fats and low-fat dairy products) have a positive effect in modifying cardiometabolic risk factors. Red meat intake correlates with increased CVD risk, mainly because of its non-protein ingredients (saturated fats). However, the way red meat is cooked and preserved matters. Thus, it is recommended to substitute red meat with poultry or fish in order to lower CVD risk. Specific amino acids have favourable results in modifying major risk factors for CVD, such as hypertension. Apart from meat, other animal-source proteins, like those found in dairy products (especially whey protein) are inversely correlated to hypertension, obesity and insulin resistance

Prevalence of statin intolerance: a meta-analysis.

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 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

Scaling Up Global Mental Health Services During the COVID-19 Pandemic and Beyond

Every health care system requires an adequate health care workforce, service delivery, financial support, and information technology. During the COVID-19 pandemic, global health systems were ill prepared to address the rising prevalence of mental health problems, especially in low-and middle-income countries (LMICs), thereby increasing treatment gaps. To close these gaps globally, task shifting and telepsychiatry should be made available and maximized, particularly in LMICs. Task shifting to nonspecialist health workers to improve essential mental health coverage and encourage effi-cient use of the available resources and technology has become the most viable strategy. Psychiatric Services 2022; 73:231-234; doi: 10.1176/appi.ps.20200077