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Atherosclerotic cardiovascular disease (ASCVD) and consequent acute coronary syndromes (ACS) are substantial contributors to morbidity and mortality across Europe. Fortunately, as much as two thirds of this disease's burden is modifiable, in particular by lipid-lowering therapy (LLT). Current guidelines are based on the sound premise that, with respect to low-density lipoprotein cholesterol (LDL-C), "lower is better for longer", and recent data have strongly emphasised the need for also "the earlier the better". In addition to statins, which have been available for several decades, ezetimibe, bempedoic acid (also as fixed dose combinations), and modulators of proprotein convertase subtilisin/kexin type 9 (PCSK9 inhibitors and inclisiran) are additionally very effective approaches to LLT, especially for those at very high and extremely high cardiovascular risk. In real life, however, clinical practice goals are still not met in a substantial proportion of patients (even in 70%). However, with the options we have available, we should render lipid disorders a rare disease. In April 2021, the International Lipid Expert Panel (ILEP) published its first position paper on the optimal use of LLT in post-ACS patients, which complemented the existing guidelines on the management of lipids in patients following ACS, which defined a group of "extremely high-risk" individuals and outlined scenarios where upfront combination therapy should be considered to improve access and adherence to LLT and, consequently, the therapy's effectiveness. These updated recommendations build on the previous work, considering developments in the evidential underpinning of combination LLT, ongoing education on the role of lipid disorder therapy, and changes in the availability of lipid-lowering drugs. Our aim is to provide a guide to address this unmet clinical need, to provide clear practical advice, whilst acknowledging the need for patient-centred care, and accounting for often large differences in the availability of LLTs between countries. [ABSTRACT FROM AUTHOR]

Lipid disorders, primarily hypercholesterolemia, are the most common cardiovascular (CV) risk factor in Poland (this applies even 3/4 of people). The low-density lipoprotein cholesterol (LDL-C) serum level is the basic lipid parameter that should be measured to determine CV risk and determines the aim and target of lipid-lowering treatment (LLT). Lipid-lowering treatment improves cardiovascular prognosis and prolongs life in both primary and secondary cardiovascular prevention. Despite the availability of effective lipid-lowering drugs and solid data on their beneficial effects, the level of LDL-C control is highly insufficient. This is related, among other things, to physician inertia and patients' fear of side effects. The development of lipidology has made drugs available with a good safety profile and enabling personalisation of therapy. Pitavastatin, the third most potent lipid-lowering statin, is characterised by a lower risk of muscle complications and new cases of diabetes due to its being metabolised differently. Thus, pitavastatin is a very good therapeutic option in patients at high risk of diabetes or with existing diabetes, and in patients at cardiovascular risk. This expert opinion paper attempts at recommendation on the place and possibility of using pitavastatin in the treatment of lipid disorders. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease is the primary complication and cause of death in patients with type 2 diabetes mellitus. Modification of cardiovascular risk factors may improve patient outcomes. Purpose: To evaluate the effectiveness of pharmacologic lipid-lowering therapy on outcomes in type 2 diabetes mellitus. Data Sources: Review of the literature. Study Selection: Randomized trials evaluating clinical outcomes of lipid-lowering treatment in patients with diabetes. Data Extraction: Studies were identified by searching the Cochrane Library, MEDLINE, meta-analyses, review articles, and inquiries to experts. The Cochrane Library and MEDLINE searches were done in September 2002. Data were abstracted onto stan-dardized forms by a single reviewer and were confirmed by a second reviewer. Data Synthesis: Meta-analysis of 6 primary prevention studies showed that lipid-lowering medications reduced risks for cardio-vascular outcomes (relative risk, 0.78 [95% CI, 0.67 to 0.89]; absolute risk reduction, 0.03 [CI, 0.01 to 0.04] in 4.3 years of treatment); 1 major cardiovascular event was prevented by treat- ing 34 to 35 patients. Meta-analysis of 8 studies of secondary prevention showed a similar relative risk (0.76 [CI, 0.59 to 0.93]) but more than twice the absolute risk reduction (0.07 [CI, 0.03 to 0.12] in 4.9 years of treatment) and a number needed to treat for benefit of 13 to 14. Most studies compared a lipid-lowering drug with placebo but did not evaluate the effect of reaching specific cholesterol levels. The benefit of lipid lowering with a fixed dose of a statin appeared to be similar regardless of starting cholesterol levels. Limitations: Target cholesterol levels and the effectiveness of dose titration (or the use of multiple agents) have not been rig-orously examined. Conclusions: In patients with type 2 diabetes, treatment with lipid-lowering agents reduces cardiovascular risk. Most patients, including those... [ABSTRACT FROM AUTHOR]

This paper aims to explore the causal relationship between genetic proxies for lipid-lowering drugs and breast and endometrial cancers using drug-target Mendelian randomization (MR). Methods: Analyses were mainly performed using inverse variance weighted (IVW), heterogeneity and horizontal pleiotropy tests, and sensitivity analysis to assess the robustness of the results and causal relationship. Results: HMGCR, APOB, and NPC1L1 increased the risk of breast cancer, LPL increased the risk of endometrial cancer, and APOC3 decreased the risk of breast and endometrial cancer. No heterogeneity or horizontal pleiotropy was detected, and nor was there any evidence of an association between other lipid-lowering drugs and breast and endometrial cancer. Conclusion: Our study demonstrated genetically that HMGCR inhibition, APOB inhibition, and NPC1L1 inhibition decrease the risk of breast cancer, LPL agonist increases the risk of endometrial cancer, and APOC3 inhibition decreases the risk of breast cancer and endometrial cancer, and these findings provide genetic insights into the potential risks of lipid-lowering drug therapy. [ABSTRACT FROM AUTHOR]

In the last two decades, statin therapy has proved to be the most potent isolated therapy for attenuation of cardiovascular risk. Its frequent use has been seen as one of the most important elements for the reduction of cardiovascular mortality in developed countries. However, the recurrent incidence of muscle symptoms in statin users raised the possibility of causal association, leading to a disease entity known as statin associated muscle symptoms (SAMS). Mechanistic studies and clinical trials, specifically designed for the study of SAMS have allowed a deeper understanding of the natural history and accurate incidence. This set of information becomes essential to avoid an unnecessary risk of severe forms of SAMS. At the same time, this concrete understanding of SAMS prevents overdiagnosis and an inadequate suspension of one of the most powerful prevention strategies of our times. In this context, the Luso-Latin American Consortium gathered all available information on the subject and presents them in detail in this document as the basis for the identification and management of SAMS. [ABSTRACT FROM AUTHOR]

The paper reviews some of the mechanisms implicated in hepatotoxicity, which is induced by an excess of lipids. The paper spans a wide variety of topics: from the molecular mechanisms of excess lipids, to the therapy of hyperlipidemia, to the hepatotoxicity of lipid-lowering drugs. NAFLD is currently the leading cause of chronic liver disease in Western countries; the molecular mechanisms leading to NAFLD are only partially understood and there are no effective therapeutic interventions. The prevalence of liver disease is constantly increasing in industrialized countries due to a number of lifestyle variables, including excessive caloric intake, unbalanced diet, lack of physical activity, and abuse of hepatotoxic medicines. Considering the important functions of cell death and inflammation in the etiology of the majority, if not all, liver diseases, one efficient therapeutic treatment may include the administration of hepatoprotective and anti-inflammatory drugs, either alone or in combination. Clinical trials are currently being conducted in cohorts of patients with different liver diseases in order to explore this theory. [ABSTRACT FROM AUTHOR]

Cinnamon is one of the world's oldest and most popular spices, and is derived from the inner bark of several tree species from the genus Cinnamomum. During the last two decades, cinnamon has demonstrated beneficial metabolic effects not only in animal experiments but also in clinical trials. Even recent meta-analyses have shown the protective effects of cinnamon on different components of metabolic syndrome and their complications. In the last 5 years, several experimental studies have unraveled the intricate molecular mechanisms underlying the antihypertensive, antihyperglycemic, lipid-lowering, weight-lowering, and cardioprotective properties of cinnamon. This review paper will discuss how cinnamon and its active components, particularly cinnamaldehyde, suppress inflammation and oxidative stress, modulate mitochondrial dysfunction, and regulate glucose uptake, insulin resistance, lipogenesis, beta-oxidation, Ca2+ signaling, and other cellar events at the molecular level. Specifically, we will delve into the molecular mechanisms involved in the metabolic effects of cinnamon to provide a deeper insight into how cinnamon can bring such beneficial effects. This review hopes to encourage the use of cinnamon in clinical settings, guide the combination of cinnamon with other drugs used to treat different components of metabolic syndrome based on their mechanism of action, and support the concept of complementary medicine for metabolic diseases. [ABSTRACT FROM AUTHOR]

Rhubarb, the Rhei radix et rhizoma (Da huang) is a member of the Polygonaceae family, included in the 2020 edition of the Chinese Pharmacopoeia, and is mainly distributed in Gansu, Sichuan, Qinghai, northwestern Yunnan, and eastern Tibet. Rhei radix et rhizoma is one of the most commonly used traditional Chinese medicines, processed into drinkable tablets in different concoctions for clinical use. Phytochemical studies showed that more than 170 compounds were isolated and identified from Rhei radix et rhizoma, including anthraquinones/anthrones (major constituents), stilbenes, chromones, flavonoids, tannins, and other compounds, etc. Rhei radix et rhizoma is an herb with a long history of traditional use and many potential therapeutic benefits. It can play the role of diarrhea, clearing heat in response to different combinations and concoctions. It is mainly used for the treatment of constipation, gastrointestinal function impairment, and other diseases. In addition, Rhei radix et rhizoma has significant antitumor, anti-inflammatory, antibacterial, hepato-renal protective, neuroprotective, hypolipidemic, and immunomodulatory activities. Its active constituents have anti-tumor, anti-inflammatory, anti-inflammatory and hepato-kidney protective properties. Although it is primarily used for gastrointestinal disorders, it may also have wider applications in various inflammatory and liver disorders. Therefore, further studies are needed to explore its full potential and mechanism of action. This paper reviews the research progress of Rhei radix et rhizoma in terms of botany, traditional use, chemistry, pharmacology, and clinical studies. It aims to provide a scientific basis for in-depth research and development of Rhei radix et rhizome resources. [ABSTRACT FROM AUTHOR]

Despite continued advances in prevention and treatment strategies, cardiovascular diseases (CVDs) remain the leading cause of death worldwide, and more effective therapeutic methods are urgently needed. Polygonatum is a traditional Chinese herbal medicine with a variety of pharmacological applications and biological activities, such as antioxidant activity, anti-inflammation, antibacterial effect, immune-enhancing effect, glucose regulation, lipid-lowering and anti-atherosclerotic effects, treatment of diabetes and anticancer effect. There has also been more and more evidence to support the cardioprotective effect of Polygonatum in recent years. However, up to now, there has been a lack of comprehensive studies on the active ingredients and their pharmacotoxicological effects related to cardiovascular diseases. Therefore, the main active components of Polygonatum (including Polysaccharides, Flavonoids, Saponins) and their biological activities were firstly reviewed in this paper. Furthermore, we summarized the pharmacological effects of Polygonatum's active components in preventing and treating CVDs, and its relevant toxicological investigations. Finally, we emphasize the potential of Polygonatum in the prevention and treatment of CVDs. [ABSTRACT FROM AUTHOR]

Background: To investigate the effect of timing of statin administration on lipid-lowering efficacy. Methods: Computer searches of Pubmed, Embase, Cochrane Library, and Web of Science databases from 1986 to 2023. The impact of administration time on the lipid-lowering efficacy of statin drugs was investigated. Following a series of screenings, a funnel plot was constructed to assess its symmetry, and Egger and Beggar tests were conducted using StataMP-64 to evaluate publication bias. Meta-analysis was performed using RevMan 5.3 to combine MD values. Results: Fifteen papers (1352 participants) met and included the criteria. The results of the meta-analysis showed that the effect of morning and evening administration time on plasma triglycerides (TG) (P > 0.05) and plasma high-density lipoprotein cholesterol (HDL-C) (P > 0.05) was not statistically significant. There were significant reductions in total cholesterol (TC) (MD: 0.15 mmol/L, 95% CI: 0.06–0.23, P < 0.01) and low-density lipoprotein cholesterol (LDL-C) (MD: 0.10 mmol/L, 95% CI: − 0.00–0.20, P < 0.01) in the night group. According to the analysis results of the half-life of statins, only short half-life statins showed that nocturnal administration reduced LDL-C (MD: 0.21 mmol/L, 95% CI: 0.09–0.33, P < 0.01) and TC (MD: 0.32 mmol/L, 95% CI: 0.18–0.46, P < 0.01) levels and was better than morning administration. Long half-life statins did not show significant differences. In addition, the administration time of short half-life statins also showed that night administration tended to reduce TG (MD: 0.16 mmol/L, 95% CI: 0.02–0.30, P < 0.05) levels. In subgroup analysis according to clinical factors in patients aged < 55 years, there was no significant difference in the timing of administration between the two groups; the efficacy of statins in lowering lipids in patients aged ≥ 55 years was significantly different in the TC group (P < 0.01) and LDL-C group (P < 0.01). The administration time of the TC group (P < 0.05) and LDL-C group (P < 0.05) in the Americas, Europe, and Asian groups was significantly different for statins. In addition, the American group also showed that the administration time of the two groups was significantly different from the TG group (P < 0.05). Conclusion: The efficacy of administering short half-life statin drugs at night in reducing plasma levels of TC, LDL-C, and TG surpasses that of morning administration. However, this study did not determine the impact of timing of statin administration in patients taking long half-life statins on the efficacy of the medication. Therefore, it is recommended to consider patient adherence when. The study was registered on PROSPERO (International Prospective Register of Systematic Reviews) as CRD42022372105 (available at https://www.crd.york.ac.uk/prospero/). [ABSTRACT FROM AUTHOR]

Ganoderma is the dried fruiting bodiy of Ganoderma lucidum (Leyss.ex Fr.) Karst. or Ganoderma sinense Zhao, Xu et Zhang, belonging to the family Polyporaceae, which grows mainly in tropical, subtropical, and temperate regions. As a traditional Chinese medicine, Ganoderma has been used in China for more than 2000 years because of its medicinal properties, such as relieving cough and asthma, providing nourishment, and strengthening. Currently, more than 470 natural compounds have been obtained from the fungus, mainly including terpenoids, steroids, alkaloids, phenols, and other types of compounds. Modern pharmacological studies have shown that Ganoderma has antitumor, anti-inflammatory, hypoglycemic, hypolipidemic, and immunomodulatory effects. It is mainly used in clinical practice for the treatment of Diabetic Nephropathy and malignant tumors, with few side effects and high safety. This paper reviews the progress of research on its chemical composition, pharmacological effects, and clinical applications, with the goal of providing a basis for the better development and utilization of Ganoderma. [ABSTRACT FROM AUTHOR]

There is a train of thought that lipid therapies may delay or limit the impact of neuronal loss and poor patient outcomes of neurodegenerative diseases (NDDs). A variety of medicines including lipid lowering modifiers (LLMs) are prescribed in NDDs. This paper summarizes the findings of clinical and observational trials including systematic reviews and meta-analyses relating to LLM use in NDDs published in the last 15 years thus providing an up-to-date evidence pool. Three databases were searched PubMed, CINAHL, and Web of Science using key terms relating to the review question. The findings confirm the benefit of LLMs in hyperlipidemic patients with or without cardiovascular risk factors due to their pleotropic effects. In NDDs LLMs are proposed to delay disease onset and slow the rate of progression. Clinical observations show that LLMs protect neurons from α-synuclein, tau, and Aβ toxicity, activation of inflammatory processes, and ultimately oxidative injury. Moreover, current meta-analyses and clinical trials indicated low rates of adverse events with LLMs when used as monotherapy. LLMs appear to have favorable safety and tolerability profiles with few patients stopping treatment due to severe adverse effects. Our collated evidence thus concludes that LLMs have a role in NDDs but further work is needed to understand the exact mechanism of action and reach more robust conclusions on where and when it is appropriate to use LLMs in NDDs in the clinic. [ABSTRACT FROM AUTHOR]

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Crestor, an important but controversial cholesterol-lowering drug, is contraindicated for use by senior and Asian patients. In this paper, we exploit this fact along with unique physician-level prescription and detailing data for statin drugs to examine the hypothesis that detailing is informative. Our tests are based on a simple model in which detailing impacts physicians' expected match utility of Crestor for different types of patients. We find strong evidence for the informative-detailing hypothesis: relative to the other patients, detailing significantly reduces physicians' likelihood of prescribing Crestor to contraindicated patients. Our results are robust to detailing being correlated with physician-specific unobserved factors and/or differential trends in individual physicians' attitudes toward Crestor. [ABSTRACT FROM AUTHOR]

Bempedoic acid is a new oral lipid-lowering therapy which has been licenced for use in the United Kingdom. It can be used alone, with a statin, or with other lipid-lowering therapies where the target level for low density lipoprotein has not been achieved with these therapies alone. Bempedoic acid with ezetimibe can be prescribed for people who are unable to tolerate statins. This combination has received NICE approval following a technology appraisal. This paper discusses the place for of bempedoic acid as a lipid lowering drug and consider the mode of action, licensed indications, adverse drug reactions and the NICE technology appraisal recommendations. [ABSTRACT FROM AUTHOR]

This paper investigates and quantifies the impact of parallel trade in markets for pharmaceuticals. The paper develops a structural model of demand and supply using data on price, sales, and the characteristics of statins in Denmark and simulates outcomes under a complete ban of parallel imports, keeping other regulatory schemes unchanged. There are two sets of key results. The first set focuses on price effects. On average, prices increase more in markets where the molecule has lost patent protection; wholesale prices for both generic and original products increase after competition from parallel importers is removed, but the final price paid by consumers (after deducting reimbursement) increases more for original products than for generics because most changes in wholesale prices are absorbed by the prevailing reimbursement rules. The second set of results reports the effects on market participants. My model takes into consideration consumers' preferences, allowing them to substitute between products. Prohibiting parallel imports induces consumers to substitute towards original products for which they have stronger preferences. In sum, banning parallel imports leads to (a) an increase in variable profits for original producers and a decrease for generic firms, (b) an increase in governmental health-care expenditures, and (c) a decrease in the welfare of Danish patients and firms. [ABSTRACT FROM AUTHOR]

Heterozygous familial hypercholesterolemia (heFH) is a common metabolic disease associated with increased cardiovascular risk. Despite treatment with the currently available lipid-lowering agents (statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors), a substantial proportion of patients with heFH does not achieve low-density lipoprotein cholesterol (LDL-C) targets. The PubMed database was reviewed for relevant papers published up to August 2020. The safety and efficacy of novel agents, namely inclisiran and bempedoic acid, that lower LDL-C levels and might be useful in the management of patients with heFH are discussed. The prolonged lipid-lowering effect of inclisiran might improve adherence to treatment in patients with heFH. Bempedoic acid provides additional reductions in LDL-C levels in patients on high-intensity statin treatment; oral administration of this agent might be attractive to some patients. However, it is important to evaluate the effects of these agents on cardiovascular morbidity before they are incorporated in the management of heFH. The cost/benefit of treatment should also be considered, given the increasing complexity of lipid-lowering treatment. [ABSTRACT FROM AUTHOR]

Introduction: Although several lipid-lowering drugs are available, they are not sufficient for some patients. Bempedoic acid is a small molecule adenosine triphosphate-citrate lyase inhibitor indicated for the treatment of adults with hypercholesterolemia.Areas Covered: We performed a systematic review of the literature using PubMed database, and the following keywords were used: 'bempedoic acid,' 'hypercholesterolemia,' and 'adenosine triphosphate citrate lyase.' The chemical property, mechanism of action, pharmacokinetics, clinical efficacy, and safety of bempedoic acid are introduced in this paper.Expert Opinion: Bempedoic acid can modulate the metabolism of cholesterol. Clinical trials indicated that bempedoic acid could significantly reduce low-density lipoprotein cholesterol levels. Bempedoic acid was well tolerated. [ABSTRACT FROM AUTHOR]

What is known and objective: Statins, also known as 3‐hydroxy‐3‐methylglutaryl‐CoA reductase inhibitors, and antidepressant drugs are frequently used in combination due to the high and growing incidence of cardiovascular diseases and psychiatric disorders worldwide. Several aspects on management, the risk of adverse events (AEs) occurrence and the potential clinically relevant pharmacokinetic (PK) and pharmacodynamic (PD) drug‐drug interactions (DDIs) between these two classes have not been well investigated. The aim of the present review was to describe the PK and PD interactions, of clinical relevance, between statins and antidepressant drugs and provide a comprehensive overview of their pharmacological features for appropriate multiple drug regimens. Methods: Relevant studies were identified through a literature search of PubMed and the Cochrane databases focusing on clinically relevant DDIs between statins and antidepressants. Only papers in English were included in the search. Results and discussion: Pharmacodynamic (PD) drug‐drug interactions (DDIs) are unlikely to occur as statins are highly selective inhibitors of HMG‐CoA reductase with no relevant effect on other enzymes or receptor systems. Despite the numerous PK studies on individual drugs belonging to statins and antidepressant agents, only a few case reports regarding specific DDIs are present in the literature and no clinical studies have been performed. PK data allow to speculate on potential DDIs, comparing the metabolic pathways, intestinal and liver transporters and elimination routes. Overall, second‐generation antidepressants, in particular citalopram, escitalopram, mirtazapine, reboxetine and venlafaxine, have weak inhibitory effects on various cytochrome (CYP) isozymes and seem to have a more advantageous DDIs profile in vivo. Conversely, nefazodone, fluoxetine, paroxetine and fluvoxamine influence considerably CYPs activity with potential effects on statins plasma levels, although pravastatin, pitavastatin and rosuvastatin are not susceptible to inhibition by any CYP. Albeit no studies have been performed on P‐glycoprotein (P‐gp), interactions of clinical relevance are unlikely. What is new and conclusion: Although DDIs with antidepressants are potentially, but rarely clinically significant, the use of antidepressants with a more favourable drug interaction profile is advisable. An evaluation on DDIs between these drugs can be useful for future PK/PD studies on drug‐drug interaction to provide clinicians with more data for appropriate multiple drug regimens. [ABSTRACT FROM AUTHOR]

Current cardiovascular disease prevention strategies are based on the management of cardiovascular risk as a continuum, redefining the therapeutic goals for each individual based on the estimated global risk profile. Given the frequent clustering of the principal cardiovascular risk factors, such as hypertension, diabetes and dyslipidaemia, in the same individual, patients are required to take multiple drugs to achieve therapeutic targets. The adoption of single pill fixed dose combinations may contribute to achieve better control of blood pressure and cholesterol compared to the separate administration of the individual drugs, mostly due to better adherence related to therapeutic simplicities. This paper reports the outcomes of an Expert multidisciplinary Roundtable. In particular, the rational and potential clinical use of the single pill fixed dose combination "Rosuvastatin-Amlodipine" for the management of concomitant hypertension/hypercholesterolemia in different clinical fields are discussed. This Expert Opinion also illustrates the importance of an early and effective management of total cardiovascular risk, highlights the substantial benefits of combining blood pressure and lipid-lowering treatments in a single-pill fixed dose combination and attempts to identify and overcome the barriers to the implementation in clinical practice of the fixed dose combinations with dual targets. This Expert Panel identifies and proposes the categories of patients who may benefit the most from this fixed dose combination. [ABSTRACT FROM AUTHOR]

Background: Treatment of CV risk factors, such as cholesterol level, represents one of the main goals to reduce atherosclerotic burden. The aim of this study was to investigate the prescriptive appropriateness of cholesterol-lowering drugs among patients who experienced an atherosclerotic CV disease (ASCVD). Methods: We investigated 155 patients who underwent cardiac rehabilitation in 2020. The European Society of Cardiology (ESC) 2021 guidelines on CV disease prevention and 2019 ESC Guidelines on dyslipidemias were followed to detect the appropriateness of prescription. SCORE2 and SCORE2-OP risk estimations were used to detect patients' CV risk profiles. Patients were divided into three groups: 1 (n = 118) patients admitted for their first CV event, 2A (n = 18) patients who experienced a previous CV event years before, and 2B (n = 19) patients admitted for a new event with a previous CV event 2 years before. Low-density lipoprotein (LDL) cholesterol level was detected at the time of admission to the hospital, during cardiac rehabilitation, and at the first visit after rehabilitation. Results: The statistics for our study participants, with a mean age of 66.1 years, were: 72.4% overweight/obese, 63.9% diabetic, 72.5% smokers, 93.0% hypertensives, and 91.7% had dyslipidemias. In group 1, only 5.1% had a low/moderate risk, 44.1% presented a high risk, and 50.8% a very high risk according to calculators. The average LDL levels were 115.8 mg/dL (2.99 mol/L) upon admission to the hospital, 66.4 mg/dL (1.72 mmol/L) at the time of cardiac rehabilitation, and 64.8 mg/dL (1.67 mmol/L) at the subsequent medical visit. In the overall group, only 36.0% had LDL < 55 mg/dL (1.42 mmol/L). In group 1, 79.4% were treated with high-intensity statin alone or plus ezetimibe; in group 2A, the percentage increased up to 87.5%, while group 2B 33.4% was treated with high-intensity statin plus ezetimibe and 33.3% were treated with PCSK9 inhibitors. Conclusions: This retrospective study confirms the importance of properly calculating CV risk profiles. The main limitations for the efficacy of lipid-lowering drugs were: patient's compliance, drugs side effects, lifestyle habits, and collaboration with a general practitioner. [ABSTRACT FROM AUTHOR]

Macrophages are the basic mediators and coordinators of various types of chronic inflammation and play a crucial role in the formation and development of atherosclerosis (AS). In the complex microenvironment of atherosclerotic plaques, macrophages of different sources are exposed to different signal stimuli and thus polarized into various subpopulations. Various types of macrophages with predominantly M1 and M2 phenotypes also play different regulatory roles in the initiation and progression of AS. Lipid-lowering drugs, mainly statins, are widely used in clinical practice, but the adverse reactions are obvious and there is a lack of personalized treatment. Emerging targeted macrophage and Traditional Chinese medicine (TCM)-related therapies can regulate the cellular microenvironment, inhibit the polarization of M1 macrophages, and promote the activation of M2 macrophages, providing new ideas for the prevention and treatment of AS. [ABSTRACT FROM AUTHOR]

We examine a class of multivariate meta-regression models in the presence of individual patient data. The methodology is well motivated from several studies of cholesterol-lowering drugs where the goal is to jointly analyze the multivariate outcomes, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and triglycerides. These three continuous outcome measures are correlated and shed much light on a subject's lipid status. One of the main goals in lipid research is the joint analysis of these three outcome measures in a meta-regression setting. Since these outcome measures are not typically multivariate normal, one must consider classes of distributions that allow for skewness in one or more of the outcomes. In this paper, we consider a new general class of multivariate skew distributions for multivariate meta-regression and examine their theoretical properties. Using these distributions, we construct a Bayesian model for the meta-data and develop an efficient Markov chain Monte Carlo computational scheme for carrying out the computations. In addition, we develop a multivariate L measure for model comparison, Bayesian residuals for model assessment, and a Bayesian procedure for detecting outlying trials. The proposed multivariate L measure, Bayesian residuals, and Bayesian outlying trial detection procedure are particularly suitable and computationally attractive in the multivariate meta-regression setting. A detailed case study demonstrating the usefulness of the proposed methodology is carried out in an individual patient data multivariate meta-regression setting using 26 pivotal Merck clinical trials that compare statins (cholesterol-lowering drugs) in combination with ezetimibe and statins alone on treatment-naïve patients and those continuing on statins at baseline. [ABSTRACT FROM AUTHOR]

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Vine tea is a popular folk tea that has been consumed in China for more than 1200 years. It is often used in ethnic medicine by ethnic groups in southwest China with at least 35 aliases in 10 provinces. In coastal areas, vine tea is mostly used to treat heatstroke, aphtha, aphonia, toothache, etc. In contrast, in the southwest inland regions, vine tea is mostly used to clear away heat and toxic materials, antiphlogosis and relieving sore-throat, lowering blood pressure and lipid levels, and alleviating fatigue. Three main species have been used as the source of vine tea, Nekemias grossedentata , Nekemias cantonensis and Nekemias megalophylla. Among them, the leaves of Nekemias grossedentata were considered as new food resource in complicance with regulations, according to the Food Safety Standards published by the Monitoring and Evaluation Department of the National Health and Family Planning Commission in China. At present, the comprehensively summary of Materia Medica on the history and source of vine tea is currently unavailable. The current article summed up the Materia Medica, species origin and pharmacological effects of all 3 major species used in vine tea to fill the knowledge gaps. We also aim to provide a reference for future research on historical textual, resource development and medicinal utilization of vine tea. Adhering to the literature screening methodology outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), this review encompasses 148 scholarly research papers from three database, paper ancient books, local chronicles and folklore through field investigations. We then comprehensively summarized and discussed research progresses in scientific and application studies of vine tea. The historical records indicated that vine tea could have been used as early as Southern and Northern Dynasties (AC 420–589). Nekemias grossedentata , Nekemias cantonensis and Nekemias megalophylla , were used to considered as vine tea in the ethnic medicine. The main phytochemicals found in three plants are flavonoids, polyphenols and terpenoids, among which dihydromyricetin (DHM) is the most important and most studied active substance. The key words " Ampelopsis grossedentata " (Synonym of Nekemias grossedentata) and "dihydromyricetin/DHM" showed the highest frequency over the last 27 year based on the research trend analysis. And the ethnopharmacology studies drawn the main activities of vine tea are antioxidant, antibacterial, hepatoprotective, neuroprotective and anti-atherosclerosis activities. This review systematically summarized and discussed vine tea from the following five aspects, history, genetic relationship, phytochemistry, research trend and ethnopharmacology. Vine tea has a long historical usage in Chinese ethnic medicine. Its outstanding therapeutic efficacies have attracted extensive attention in other places in the world at present. Nekemias cantonensis and Nekemias megalophylla are quite similar to Nekemias grossedentata in terms of many aspects. However, the current research has a narrow focus on mainly Nekemias grossedentata and DHM. We propose that future studies could be carried out to determine the synergistic effect of multi-components and multi-targets of vine tea including all 3 species to provide valuable knowledge. [Display omitted] • Vine tea, renowned in China, exhibits an array of pharmacological effects. • Dihydromyricetin (DHM), abundant in vine tea, is a key focus of scientific research. • N. cantonensis, N. megalophylla , and N. grossedentata are identified as vine tea sources. • Promising results in DHM clinical trials warrant further robust investigations. • Future research opportunities lie in the exploration of other bioactive components in vine tea. [ABSTRACT FROM AUTHOR]

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Patients with glioblastoma multiforme (GBM) have an average life expectancy of approximately 15 months. Recently, statins have emerged as a potential adjuvant cancer therapy due to their ability to inhibit cell proliferation and induce apoptosis in many types of cancer. The exact mechanisms that mediate the inhibitory actions of statins in cancer cells are largely unknown. The purpose of this proceeding paper is to discuss some of the known anticancer effects of statins, while focusing on GBM therapy that includes adjunct therapy of statins with chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

Berberine (BBR), isolated from a Chinese herb, is identified as a new cholesterol‐lowering small molecule, and hundreds of berberine derivatives have been obtained for optimization of their hypolipidemic activities in recent years. However, so far there is no available quantitative structure–activity relationship (QSAR) model used for the development of novel BBR analogues with hypolipidemic activities, mainly due to lack of lipid‐lowering molecular mechanisms and target identification of BBR. In this paper, the tactics using ligand efficiency indice instead of pIC50 as the activity could be adopted for the development of BBR QSAR models. A series of 59 BBR derivatives with hypolipidemic activities have been studied and split randomly into three sets of training and test sets. Statistical quality of most building models shows obviously robust. Best calculated model that employs LLE indice as the activity (Model 6) has the following statistical parameters: for training set R2 = .984, Q2 = 0.981, RMSE = 0.1160, and for test set R2 = .989, RMSE = 0.0067. This model would be used for the development of novel BBR analogues with lipid‐lowering activities as a hit discovery tool. [ABSTRACT FROM AUTHOR]

Statins are the first line of pharmacologic treatment for the management of hypercholesterolemia in patients at risk for atherosclerotic cardiovascular (CV) disease. In recent years, several randomized, controlled trials (RCTs) and observational studies have reported increased risk for new-onset type 2 diabetes mellitus (T2D) with statin treatment, particularly with use of high-intensity statins that reduce low-density lipoprotein cholesterol (LDL-C) by 50% or more. This paper summarizes the data from RCTs and observational studies for statin-associated T2D risk, and puts into perspective this evidence, weighed against the established benefits of statin therapy for CV risk reduction. In RCTs, the increase in T2D risk with statin therapy appears to be attributable mainly to those with major T2D risk factors. The increase in incidence of T2D in those with major risk is approximately 25% for statin use, compared to placebo, and for intensive statin therapy compared to moderate-intensity statin therapy. However, in those with major T2D risk factors, the number of CV disease events prevented for each excess case of T2D is close to or greater than one, indicating that the risk-benefit ratio still strongly favors use of statin therapy, or intensive statin therapy, for patients with sufficient CV disease risk to warrant cholesterol-lowering drug therapy. Recommendations are summarized for evaluation of the T2D risk factor profile before initiation of and during statin therapy. In addition, the importance of lifestyle management and other preventive measures is emphasized for management of risks for both T2D and CV disease events in patients receiving statin therapy. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is a major cause of morbidity and mortality in patients with type 2 diabetes. For this reason, there is a great deal of interest in determining how therapies commonly used to treat patients with diabetes impact cardiovascular outcomes. Results from recently completed cardiovascular outcomes trials of diabetes agents from several medication classes are leading to a sea change in how we think about diabetes treatment. The primary focus of this paper is to review recently completed and ongoing diabetes medication cardiovascular outcomes trials. We also review cardiovascular outcome evidence for other classes of medications commonly used in patients with diabetes (i.e., aspirin, anti-hypertensive agents, lipid-lowering agents, and weight loss medications). [ABSTRACT FROM AUTHOR]

An introduction to an analysis of data from the Global Burden of Disease study which predicts that the global prevalence of cardiovascular disease will double between 2025 and 2060 is presented.

Nonalcoholic fatty liver disease (NAFLD) is a typical metabolic disease caused by excessive accumulation of lipid in the liver. Lovastatin (Lov) is a representative of a classic lipid-lowering drug, but the drug has a lack of targeting, and the toxic and side effects are serious. Reactive oxygen species (ROS), which can lead to a "second strike" of NAFLD, eventually lead to cirrhosis and hepatic cancer. Therefore, a H2O2-responsive and self-fluorescence prodrug-nanosystem (PBI-Lov) has successfully been constructed. While consuming ROS and leading to breaking of the oxalate bond, it will result in the release of lovastatin. Negatively charged phosphatidylserine (PS) was coated on PBI-Lov to prepare PS-PBI-Lov nanoparticles. The uptake of PS-PBI-Lov nanoparticles could be increased both in HepG2 cells and RAW264 7 cells. Most importantly, these fluorescence nanoparticles realized rapid, real-time and high-precision detection in tetracycline mice. PS-PBI-Lov nanoparticles effectively targeted the liver, and decreased both lipid accumulation and vacuole structures in the liver, reducing the degree of fibrosis, and effectively reversing the NAFLD. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is the leading cause of death in the United States. Hypercholesterolemia is a principal modifiable risk factor for the primary prevention of CVD. In addition to lifestyle modification, statins are an important tool to reduce risk for CVD in selected patients. A useful strategy to identify candidates for statins is to estimate the 10-year risk for CVD through the use of a validated risk calculator. Commonly used calculators include the Framingham risk score and the pooled cohort equation. Multiple randomized controlled trials have shown that statins reduce the risk for CVD in patients without known CVD. Two recent guidelines have proposed an approach to the use of statins in primary prevention of CVD. The American College of Cardiology/American Heart Association and the U.S. Department of Veterans Affairs guidelines form the basis for this discussion. The guidelines differ on the use of advanced testing to modify the 10-year CVD risk estimate and on the need for low-density lipoprotein cholesterol targets to establish the efficacy of statins. Advanced testing with coronary artery calcium measurement may be helpful for patients who are potentially eligible for statin therapy but who are uncertain if they wish to take a statin. In this paper, 2 experts, a preventive cardiologist and a general internist, discuss their approach to the use of statins for primary prevention of CVD and how they would apply the guidelines to an individual patient. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular illness and gallstones are closely related. Our goal was to determine whether gallstones and the updated LE8 score, which measures cardiovascular health among US adults, are related. Methods: 3,570 adults participated in the 2017–2018 National Health and Nutrition Examination Survey, which provided the data for our study. Based on the criterion provided by the American Association for Cardiovascular Health (AHA), LE8 score (range 0–100) was calculated and classified as low (0–49), moderate (50–79), and high (80–100) cardiovascular health. Gallstones were derived from the questionnaire. Multivariate logistic modeling explored the independent relationship between LE8 score and gallstones. Results: There was a negative correlation between LE8 score and gallstones. Specifically, the odds of gallstones dropped by 15% for each 10-unit increase in LE8 score (OR = 0.85; 95% CI, 0.77–0.94). Smooth curve fitting detected a saturation effect between LE8 score and gallstones, with a minimum threshold of 66.25 points associated with both. There was a noticeably stronger inverse relationship between gallstones and LE8 score in those under 60 years of age and not taking antihypertensive or lipid-lowering drugs. Conclusions: Lower LE8 scores may be a potential risk factor for the development of gallstones and could also be a target for risk assessment and intervention. [ABSTRACT FROM AUTHOR]

Homozygous familial hypercholesterolemia (HoFH), is a rare genetic disorder characterized by dual mutations in the low-density lipoprotein receptor (LDLR) gene, leading to dysfunctional or absent LDLRs, often accompanied by severe premature Atherosclerotic Cardiovascular Disease (ASCVD) and exhibiting refractoriness to aggressive pharmacological interventions. Double filtration plasmapheresis (DFPP), a form of lipoprotein apheresis (LA), has been effectively utilized as an adjunctive treatment modality to reduce serum LDL-C levels in refractory cases of HoFH. Here, we report a case of a 36-year-old female with HoFH who developed xanthomas on her limbs and waist at age 7. Despite maximum-tolerated doses of statins from age 32, combined with ezetimibe and evolocumab, her LDL-C levels remained critically elevated at 12–14 mmol/L. Her genetic testing confirmed a homozygous LDLR mutation. At 35 years old, she experienced exertional chest pain, and percutaneous coronary intervention revealed severe calcific left main stenosis, necessitating stent implantation. Subsequently, she initiated once every 1–2 months DFPP. Pre-DFPP, her LDL-C and total cholesterol (TC) levels were 13.82 ± 3.28 and 15.45 ± 0.78 mmol/L, respectively. Post-DFPP, her LDL-C and TC levels significantly decreased to 2.43 ± 0.33 mmol/L (81.76 ± 4.11% reduction) and 3.59 ± 0.41 mmol/L (76.76 ± 2.75% reduction), respectively. Lipoprotein (a) and triglycerides also decreased by 89.10 ± 1.39% and 42.29 ± 15.68%,respectively. Two years later, there was no progression of coronary artery disease, and her symptoms and xanthomas regressed significantly. Collectively, DFPP effectively reduces LDL-C levels in refractory cases of HoFH and contributes to delaying ASCVD progression, representing an efficacious adjunctive therapeutic modality. [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of type 2 diabetes mellitus is somewhat associated with lipid metabolism. We aim to assess the impact of lipid-lowering drugs (HMGCR inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitors) on type 2 diabetes mellitus and its complications through a two-sample Mendelian randomization (MR) study. Method: We identified suitable genetic instruments from the GWAS database that represent the expression levels of three genes, interpreting reduced genetically proxied gene expression as indicative of lipid-lowering drug use. We evaluated the causal relationships among these variables employing a two-sample Mendelian randomization approach, with the Inverse Variance Weighted (IVW) analysis serving as the primary method. Coronary artery disease was utilized as a positive control to validate the reliability of the selected genetic instruments. Result: Increased genetically proxied HMGCR expression is significantly associated with a reduced risk of type 2 diabetes mellitus (OR = 0.64, 95%CI = 0.55–0.74), which was replicated in the FinnGen study with consistent results (OR = 0.65, 95%CI = 0.53–0.80). Increased genetically proxied HMGCR expression is associated with a reduced risk of diabetic retinopathy (OR = 0.23, 95%CI = 0.12–0.44) and diabetic nephropathy (OR = 0.35, 95%CI = 0.17–0.71). In contrast, increased genetically proxied PCSK9 expression is associated with a decreased risk of diabetic coma (OR = 0.70, 95%CI = 0.50–0.98), diabetic neuropathy (OR = 0.24, 95%CI = 0.14–0.42), diabetic retinopathy (OR = 0.67, 95%CI = 0.48–0.96), diabetic cardiovascular diseases (OR = 0.62, 95%CI = 0.38–0.99), and diabetic nephropathy (OR = 0.62, 95%CI = 0.41–0.95). Conclusions: This Mendelian randomization study suggests an association between HMGCR and the pathogenesis of type 2 diabetes mellitus, with increased genetically proxied HMGCR expression reducing the risk of type 2 diabetes mellitus, while PCSK9 and NPC1L1 show no significant association with type 2 diabetes mellitus. These findings may offer more reasonable lipid-lowering drug options for patients with dyslipidemia. Highlights: • Many studies have found that certain lipid-lowering drugs increase the risk of some diseases. • Observational study finds HMGCR inhibitors increase the risk of type 2 diabetes mellitus. •HMGCR inhibitor use increased the risk of type 2 diabetes in both of two different populations. [ABSTRACT FROM AUTHOR]

Background: The impact on cardiovascular health is lost when a patient does not obtain a newly prescribed lipid-lowering medication, a situation termed "initial medication nonadherence" (IMN). This research summarizes the published evidence on the prevalence, associated factors, consequences, and solutions for IMN to prescribed lipid-lowering medication in the United States. Methods: A systematic literature search using PubMed and Google Scholar, along with screening citations of systematic reviews, identified articles published from 2010 to 2021. Studies reporting results of IMN to lipid-lowering medications were included. Studies that evaluated non-adult or non-US populations, used weaker study designs (e.g., case series), or were not written in English were excluded. Results: There were 19 articles/18 studies that met inclusion and exclusion criteria. Estimates of the prevalence of IMN to newly prescribed lipid-lowering medications ranged from 10 to 18.2% of patients and 1.4–43.8% of prescriptions (n = 9 studies). Three studies reported prescriber and patient characteristics associated with IMN. Hispanic ethnicity, Black race, lower Charlson Comorbidity Index score and no ED visits or hospitalization were associated with IMN. Lipid lowering prescriptions from primary care providers were also associated with IMN. Four studies described patient-reported reasons for IMN, including preference for lifestyle modifications, lack of perceived need, and side effect concerns. Four intervention studies reported mixed results with automated calls, live calls, or letters. One study reported worse clinical outcomes in patients with IMN: higher levels of low-density lipoprotein and greater risk of emergency department visits. Conclusions: Up to one-fifth of patients fail to obtain a newly prescribed lipid-lowering medication but there is limited information about the clinical consequences. Future research should assess outcomes and determine cost-effective approaches to address IMN to lipid-lowering therapy. [ABSTRACT FROM AUTHOR]

Background: Systemic therapeutics targeting the peroxisome proliferator-activated receptors have been found to be beneficial in the treatment of diabetic retinopathy. In this paper, we provide a rationale for the use of these therapeutics as intraocular agents. In addition, we introduce the peroxisome proliferator-activated receptors and describe their functions in response to the drugs. Discussion: Based on the evidence of large-scale clinical studies investigating the systemic administration of fenofibrate, this ligand for peroxisome proliferator-activated receptor-α is potentially a good candidate for intraocular delivery. Here, we describe the mechanisms by which it might be acting to improve diabetic retinopathy, its relative safety and we speculate on how it could be developed for intraocular delivery. Summary: In this paper, we provide a rationale for the further investigation of peroxisome proliferator-activated receptor-α agonists as intraocular agents for the treatment of diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Background: The WHO Foundation Collaborating Centre for International Drug Monitoring (Uppsala Monitoring Centre [UMC]) has received many individual case safety reports (ICSRs) associating HMG-CoA reductase inhibitor drug (statin) use with the occurrence of muscle damage, including rhabdomyolysis, and also peripheral neuropathy. A new signal has now appeared of disproportionally high reporting of upper motor neurone lesions.Aim and Scope: The aim of this paper is to present the upper motor neurone lesion cases, with other evidence, as a signal of a relationship between statins and an amyotrophic lateral sclerosis (ALS)-like syndrome. The paper also presents some arguments for considering that a spectrum of severe neuromuscular damage may be associated with statin use, albeit rarely. The paper does not do more than raise the signal for further work and analysis of what must be regarded as a potentially very serious and perhaps avoidable or reversible adverse reaction, though it also suggests action to be taken if an ALS-like syndrome should occur in a patient using statins.Methods: The 43 reports accounting for the disproportional reports in Vigibase (the database of the WHO Programme for International Drug Monitoring) are summarised and analysed for the diagnosis of an ALS-like syndrome. The issues of data quality and potential reporting bias are considered.Results: 'Upper motor neurone lesion' is a rare adverse event reported in relationship to drugs in Vigibase (a database containing nearly 4 million ICSRs). Of the total of 172 ICSRs on this reported term, 43 were related to statins, of which 40 were considered further: all but one case was reported as ALS. In 34/40 reports a statin was the sole reported suspected drug. The diagnostic criteria were variable, and seven of the statin cases also had features of peripheral neuropathy. Of a total of 5534 ICSRs of peripheral neuropathy related to any drug in Vigibase, 547 were on statins. The disproportional reporting of statins and upper motor neurone lesion persisted after age stratification, and such disproportionality was not seen for statins and Parkinson's disease, Alzheimer's disease, extrapyramidal disorders, or multiple sclerosis-like syndromes.Discussion: Because the cases were sometimes atypical we propose the use of the term 'ALS-like syndrome' and speculate whether this is part of a spectrum of rare neuromuscular damage. The diagnosis of ALS is often problematic, and the insidiousness and chronicity of the disease make causality with a drug difficult to assess. The disproportionally high reporting makes this an important signal nevertheless, since ALS is serious clinically and statins are so widely used. Wide use of the statins also makes a chance finding more probable, but is unlikely to cause disproportional reporting when there are no obvious biases identified.Conclusion: We emphasise the rarity of this possible association, and also the need for further study to establish whether a causal relationship exists. We do advocate that trial discontinuation of a statin should be considered in patients with serious neuromuscular disease such as the ALS-like syndrome, given the poor prognosis and a possibility that progression of the disease may be halted or even reversed. [ABSTRACT FROM AUTHOR]

Problem-based learning (PBL) within a tutorial is the core element in a 6-week block course "Basics in Drug Therapy" recently introduced into the medical curriculum of an eastern German university. Under the supervision of one tutor a group of 6–9 students solved a total of six clinical cases related to drugs used in general anaesthetics; to analgetic/antiphlogistic, antihypertensive, cardiovascular and lipid-lowering drugs; to drugs acting on the central nervous system; and to intoxicating agents. By answering questionnaires students and tutors extensively evaluated each individual case as well as the whole block course. Factors evaluated also included students' and tutors' behaviour during sessions. The purpose of the analysis was to identify factors associated with the students' perception of tutorials with the aim of improving future courses. The ratings which tutorials, cases and tutor performance received by the students differed significantly between 14 groups that could be analysed. A ranking order of groups was established according to the scores they gave for the cases and the three groups with top ratings were further compared with the three groups with lowest ratings. We found significant differences between the two groups in their assessment of tutor performance and perception of team-work during tutorials. The tutors of the groups giving top ratings were considered to have more effectively supported the students' work during tutorials. Furthermore, self-assessment of the tutors judging their own ability to facilitate PBL correlated with their familiarity with case content. The marks achieved in the first national exam (i.e. "Physikum", equivalent to medical school entrance exams), performance in triple jump examination and multiple choice test at the end of the course, or marks obtained in the first state board exam after the course, did not differ between the two groups. From students' point of view, the main characteristics for a good tutorial as far as tutors are concerned consist of allowing enough time for discussion, accepting students as partners, refraining from interference and having expertise. As a consequence we will increase our efforts to optimise case quality as well as support and training of tutors in order to improve our new PBL course. [ABSTRACT FROM AUTHOR]

UV/chlorine, as a novel disinfection method, has attracted great interest due to its effective removal for pathogenic microorganism and degradation of trace organic contaminants existed in water environment. This paper investigated the degradation kinetics and pathways of Bezafibrate (BZF), a typical antilipemic drug, during UV/chlorine process. The results showed that 92.3% of BZF was degraded after 20 min in UV/chlorine process. This indicated HO• and reactive chlorine species (RCSs) formed in UV/chlorine played the dominant role in degrading BZF. Observed rate constants of BZF degradation ( k ) in UV/chlorine process increased linearly in a wide chlorine dosage from 0.1 to 1.0 mM, which implied that ClO• generated from the reactions of chlorine with HO• and Cl• could react with BZF rapidly. The steady-state kinetic modeling result proved this deduction and the rate constant of ClO• with BZF was fitted to be 5.0 × 10 M s. k was affected by Cl and HA. The total contribution of RCSs (including Cl•, Cl•, and ClO•) to the degradation of BZF was determined to be ~ 80%, which is much higher than that of HO•. Thirteen degradation products of BZF were identified by LC-MS/MS. Initial degradation products were arisen from hydroxylation, chlorine substitution and cyclization by HO• and RCSs, and then further oxidized to generate acylamino cleavage and demethylation products. [ABSTRACT FROM AUTHOR]

We have examined the regression effect and its magnitude under the Gaussian distributional assumption. The impact and implication of regression to the mean on the analysis of medical investigations was discussed. For simplicity, we called the approach adjusting for the regression effect a two-stage procedure and noted its relationship to the analysis of covariance model for comparing treatment groups. We also proposed to examine the correlation structure among repeated measurements in the absence of any external interventions through a model more realistic than the one assuming equal correlations. The proposed structure led us to investigate ways to reduce or eliminate regression effect via study designs when patient selection is inevitable. Two examples were given to help illustrate the discussion in this paper. [ABSTRACT FROM AUTHOR]