Potential of niacin skin flush response in adolescent depression identification and severity assessment: a case-control study.

BACKGROUND: The diagnosis of adolescent Depressive Disorder (DD) lacks specific biomarkers, posing significant challenges. This study investigates the potential of Niacin Skin Flush Response (NSFR) as a biomarker for identifying and assessing the severity of adolescent Depressive Disorder, as well as distinguishing it from Behavioral and Emotional Disorders typically emerging in childhood and adolescence(BED). METHODS: In a case-control study involving 196 adolescents, including 128 Depressive Disorder, 32 Behavioral and Emotional Disorders, and 36 healthy controls (HCs), NSFR was assessed. Depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9) and anxious symptoms with the Generalized Anxiety Disorder 7-item scale (GAD-7). Pearson correlation analysis determined the relationships between NSFR and the severity of depression in DD patients. Receiver Operating Characteristic (ROC) was used to identify DD from BED integrating NSFR data with clinical symptom measures. RESULTS: The adolescent Depressive Disorder group exhibited a higher rate of severe blunted NSFR (21.4%) compared to BED (12.5%) and HC ( 8.3%). Adolescent Depressive Disorder with psychotic symptoms showed a significant increase in blunted NSFR (p = 0.016). NSFR had negative correlations with depressive (r = -0.240, p = 0.006) and anxious (r = -0.2, p = 0.023) symptoms in adolescent Depressive Disorder. Integrating NSFR with three clinical scales improved the differentiation between adolescent Depressive Disorder and BED (AUC increased from 0.694 to 0.712). CONCLUSION: The NSFR demonstrates potential as an objective biomarker for adolescent Depressive Disorder, aiding in screening, assessing severity, and enhancing insights into its pathophysiology and diagnostic precision.

Lipid-lowering therapies for cardiovascular disease prevention and management in primary care: PEER umbrella systematic review of systematic reviews.

OBJECTIVE: To assess the benefits and harms of lipid-lowering therapies used to prevent or manage cardiovascular disease including bile acid sequestrants (BAS), ezetimibe, fibrates, niacin, omega-3 supplements, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, and statins. DATA SOURCES: MEDLINE, the Cochrane Database of Systematic Reviews, and a grey literature search. STUDY SELECTION: Systematic reviews of randomized controlled trials published between January 2017 and March 2022 looking at statins, ezetimibe, PCSK9 inhibitors, fibrates, BAS, niacin, and omega-3 supplements for preventing cardiovascular outcomes were selected. Outcomes of interest included major adverse cardiovascular events (MACE), cardiovascular mortality, all-cause mortality, and adverse events. SYNTHESIS: A total of 76 systematic reviews were included. Four randomized controlled trials were also included for BAS because no efficacy systematic review was identified. Statins significantly reduced MACE (6 systematic reviews; median risk ratio [RR]=0.74; interquartile range [IQR]=0.71 to 0.76), cardiovascular mortality (7 systematic reviews; median RR=0.85, IQR=0.83 to 0.86), and all-cause mortality (8 systematic reviews; median RR=0.91, IQR=0.88 to 0.92). Major adverse cardiovascular events were also significantly reduced by ezetimibe (3 systematic reviews; median RR=0.93, IQR=0.93 to 0.94), PCSK9 inhibitors (14 systematic reviews; median RR=0.84, IQR=0.83 to 0.87), and fibrates (2 systematic reviews; mean RR=0.86), but these interventions had no effect on cardiovascular or all-cause mortality. Fibrates had no effect on any cardiovascular outcomes when added to a statin. Omega-3 combination supplements had no effect on MACE or all-cause mortality but significantly reduced cardiovascular mortality (5 systematic reviews; median RR=0.93, IQR=0.93 to 0.94). Eicosapentaenoic acid ethyl ester alone significantly reduced MACE (1 systematic review, RR=0.78) and cardiovascular mortality (2 systematic reviews; RRs of 0.82 and 0.82). In primary cardiovascular prevention, only statins showed consistent benefits on MACE (6 systematic reviews; median RR=0.75, IQR=0.73 to 0.78), cardiovascularall-cause mortality (7 systematic reviews, median RR=0.83, IQR=0.81 to 0.90), and all-cause mortality (8 systematic reviews; median RR=0.91, IQR=0.87 to 0.91). CONCLUSION: Statins have the most consistent evidence for the prevention of cardiovascular complications with a relative risk reduction of about 25% for MACE and 10% to 15% for mortality. The addition of ezetimibe, a PCSK9 inhibitor, or eicosapentaenoic acid ethyl ester to a statin provides additional MACE risk reduction but has no effect on all-cause mortality.

A Systematic Review of Cost-Effectiveness of Non-Statin Lipid-Lowering Drugs for Primary and Secondary Prevention of Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus.

Although studies of nonstatin lipid-lowering therapies have demonstrated cardiovascular benefits; whether these benefits provide good value has not been evaluated in type 2 diabetes mellitus patients. A systematic review was performed to include studies on the cost-effectiveness of non-statin lipid-lowering therapies in type 2 diabetes mellitus patients with/without cardiovascular disease. Thirteen studies were included; ezetimibe (n = 8), proprotein convertase subtilisin/kexin type 9 inhibitors (n = 4), fenofibrate (n = 2), nicotinic acid (n = 1), extended-release niacin/laropiprant (n = 1), and icosapent ethyl (n = 1). Six studies considered ezetimibe + statin to be a cost-effective compared to statins monotherapy, three studies suggested that proprotein convertase subtilisin/kexin type 9inhibitors + statins were not cost-effective compared to statin + ezetimibe. Fenofibrate was a cost-effective either as monotherapy or combined with a statin compared to statin or fenofibrate monotherapy. Nicotinic acid and proprotein convertase subtilisin/kexin type 9 compared to statin monotherapy were also cost-effective. Icosapent ethyl was cost-effective compared to standard care but not using the wholesale acquisition cost.

Identification of adolescent patients with depression via assessment of the niacin skin flushing response.

BACKGROUND: Depressive disorder (DD) affects approximately 20 % of adolescents worldwide, but it is underdiagnosed due to the lack of objective biomarkers. Niacin skin flushing response (NSFR) is an objective and noninvasive biomarker of adult depression; however, its effectiveness has not been assessed in adolescents. METHODS: This study included 198 adolescents with 50 % healthy controls (HC). Linear mixed-effects model and multiple linear regression analyses were performed to assess differences in NSFR between the DD and HC groups. Logistic regression models based on NSFR were constructed, and the area under curve (AUC) was calculated to evaluate the performance of models. Spearman correlations were calculated to assess the relationships between NSFR and disease duration and hormone levels associated with puberty. RESULTS: Adolescents with DD displayed significantly attenuated and delayed NSFR compared to HC. NSFR effectively distinguished DD patients from HC with AUC values of 0.719 (sensitivity = 0.844) and 0.721 (sensitivity = 0.829) determined in the discovery and validation sets, respectively. Within the DD group, the maximum degree of NSFR was negatively correlated with the disease duration (r = -0.28, p = 0.011), and the overall degree of NSFR was positively associated with prolactin (r = 0.29, p = 0.039) and thyroxine (r = 0.29, p = 0.027) levels. LIMITATIONS: Future investigations will be necessary to confirm our results in an independent sample set. CONCLUSIONS: This study provides the first evidence of the utility of NSFR as an objective auxiliary diagnostic biomarker for adolescent depression. It provides new clues to understand the pathophysiology of the disease, and helps promote precise diagnosis, treatment, and prognostic evaluation of adolescent depression.

Assessment of dietary nutrient intake and its relationship to the nutritional status of children with congenital heart disease in Guangdong province of China.

BACKGROUND AND OBJECTIVES: Congenital heart disease (CHD) is the common congenital malformations in children and cause malnutrition. We determine the association between dietary nutrient intake and nutritional status of children with CHD. METHODS AND STUDY DESIGN: 428 children of age 1-10 years with CHD admitted. The dietary nutrient intake was recorded after 3 days of 24-h recall. The growth and nutritional status of children were evaluated using anthropometric measurements and z-scores. RESULTS: The prevalence of malnutrition was 37.6% in CHD. 57.8%, 12.6%, 43.8%, and 40.6% of children did not meet their requirements for energy, protein, fat, and carbohydrate, respectively. The prevalence of insufficient intake was 88.3% for calcium, 35.9% for magnesium, 21.9% for iron, and 12.5% for zinc. 15%-86% of children did not meet vitamin requirements. 85.2% and 53.9% of children did not meet their requirements for vitamin A and vitamin C. The prevalence of insufficient intake was 39.1% for thiamin, 24.2% for riboflavin, 15.6% for niacin and 28.1% for vitamin E. Compared with the normal nutrition group, malnutrition group had a relatively lower intake of proteins, iron, zinc and vitamin E. CONCLUSIONS: An obvious deficiency of dietary nutrient intake was found among children with CHD, especially CHD with malnutrition. Dietary intake related to the nutritional status of children with CHD. The gap between actual consumption and recommendation indicates a need for improved nutritional counseling and monitoring. Early interventions targeting the dietary intakes of children with CHD may be a benefit for long-term effects associated with nutritional status.

Relative validity of a mobile AI-technology-assisted dietary assessment in adolescent females in Vietnam.

BACKGROUND: There is a gap in data on dietary intake of adolescents in low- and middle-income countries (LMICs). Traditional methods for dietary assessment are resource intensive and lack accuracy with regard to portion-size estimation. Technology-assisted dietary assessment tools have been proposed but few have been validated for feasibility of use in LMICs. OBJECTIVES: We assessed the relative validity of FRANI (Food Recognition Assistance and Nudging Insights), a mobile artificial intelligence (AI) application for dietary assessment in adolescent females (n = 36) aged 12-18 y in Vietnam, against a weighed records (WR) standard and compared FRANI performance with a multi-pass 24-h recall (24HR). METHODS: Dietary intake was assessed using 3 methods: FRANI, WR, and 24HRs undertaken on 3 nonconsecutive days. Equivalence of nutrient intakes was tested using mixed-effects models adjusting for repeated measures, using 10%, 15%, and 20% bounds. The concordance correlation coefficient (CCC) was used to assess the agreement between methods. Sources of errors were identified for memory and portion-size estimation bias. RESULTS: Equivalence between the FRANI app and WR was determined at the 10% bound for energy, protein, and fat and 4 nutrients (iron, riboflavin, vitamin B-6, and zinc), and at 15% and 20% bounds for carbohydrate, calcium, vitamin C, thiamin, niacin, and folate. Similar results were observed for differences between 24HRs and WR with a 20% equivalent bound for all nutrients except for vitamin A. The CCCs between FRANI and WR (0.60, 0.81) were slightly lower between 24HRs and WR (0.70, 0.89) for energy and most nutrients. Memory error (food omissions or intrusions) was ∼21%, with no clear pattern apparent on portion-size estimation bias for foods. CONCLUSIONS: AI-assisted dietary assessment and 24HRs accurately estimate nutrient intake in adolescent females when compared with WR. Errors could be reduced with further improvements in AI-assisted food recognition and portion estimation.

Plasma acetylcholine and nicotinic acid are correlated with focused preference for photographed females in depressed males: an economic game study.

Interpersonal difficulties are often observed in major depressive disorder (MDD), while the underlying psychological and biological mechanisms have not yet been elucidated. In the present case-control study, a PC-based trust game was conducted for 38 drug-free MDD patients and 38 healthy controls (HC). In the trust game, participants invested money in a partner (trusting behaviors), and also rated each partner's attractiveness (preference for others). In addition, blood biomarkers including metabolites were measured. Both MDD and HC males exhibited more trusting behaviors compared to females. MDD males' preference for ordinary-attractive partners (lay-person photographs) was lower than HC males, whereas their preference for high-attractive females (fashion-model photographs) was similar levels to HC males. This tendency in MDD males could reflect a "focused (narrowed) preference for females". As for blood biomarker analysis, the levels of 37 metabolites including acetylcholine, AMP, GMP, nicotinic acid and tryptophan were significantly different between two groups. Interestingly, among male participants, acetylcholine and nicotinic acid were negatively correlated with the level of focused preference for photographed females. In sum, we have revealed some behavioral, psychological and biological traits of trusting behaviors and preference for others especially in MDD males. Larger studies should be conducted to validate our preliminary findings.

Effectiveness of Levoamlodipine Maleate for Hypertension Compared with Amlodipine Besylate: a Pragmatic Comparative Effectiveness Study.

PURPOSE: Antihypertensive treatment is the most important method to reduce the risk of cardiovascular events in hypertensive patients. However, there is scant evidence of the benefits of levoamlodipine maleate for antihypertensive treatment using a head-to-head comparison in the real-world. This study aims to examine the effectiveness of levoamlodipine maleate used to treat outpatients with primary hypertension compared with amlodipine besylate in a real-world setting. METHODS: This was a pragmatic comparative effectiveness study carried out at 110 centers across China in outpatients with primary hypertension treated with levoamlodipine maleate or amlodipine besylate, with 24 months of follow-up. The primary outcomes used for evaluating the effectiveness were composite major cardiovascular and cerebrovascular events (MACCE), adverse reactions, and cost-effectiveness. RESULTS: Among the included 10,031 patients, there were 482 MACCE, 223 (4.4%) in the levoamlodipine maleate group (n = 5018) and 259 (5.2%) in the amlodipine besylate group (n = 5013) (adjusted hazard ratio = 0.90, 95%CI: 0.75-1.08, P = 0.252). The levoamlodipine maleate group had lower overall incidences of any adverse reactions (6.0% vs. 8.4%, P < 0.001), lower extremity edema (1.1% vs. 3.0%, P < 0.001) and headache (0.7% vs. 1.1%, P = 0.045). There was a nearly 100% chance of the levoamlodipine maleate being cost-effective at a willingness to pay threshold of 150,000 Yuan per quality-adjusted life years (QALYs) gained, resulting in more QALYs (incremental QALYs: 0.00392) and cost savings (saving 2725 Yuan or 28.8% reduction in overall costs) per patient. CONCLUSION: In conclusion, levoamlodipine maleate could reduce cost by 29% with a similar MACCE incidence rate and lower occurrence of adverse reactions (especially edema and headache) compared with amlodipine besylate. TRIAL REGISTRATION: Clinicaltrials.gov NCT01844570 registered at May 1, 2013.

Sociodemographic Factors Associated with Dietary Intake of Thiamine, Riboflavin, and Niacin among Chinese Adults in 2015.

OBJECTIVE: To estimate the association between three B-vitamin intakes and sociodemographic factors among adults in China. METHODS: We derived our data from the China Health and Nutrition Survey (CHNS) among 12,241 individuals aged 18-64 years. Log binomial regression was used to estimate adjusted prevalence ratios for factors associated with the inadequate intake of B-vitamins. RESULTS: Females with low incomes and living in the north had a higher prevalence of inadequate riboflavin intake than those with high incomes and living in the south. Both males and females living in a village had a higher prevalence of inadequate riboflavin intake than adults living in a city. Adults with low income, low education, and living in the north or in a village had a higher prevalence of inadequate niacin intake than adults with a high income, high education, and living in the south or in a city. CONCLUSION: We found that income, region, and area of residence were associated with riboflavin intake. Education, income, region, and area of residence were associated with niacin intake. Well-tailored strategies and policies are needed to improve nutritional status in China.

Impurity profiling high-performance-thin-layer chromatography method involving the assay of essential human micronutrient niacin with eco-scale assessment.

Currently, analytical scientists are paying special attention to reducing reliance on hazardous chemicals in various analytical methods. By embracing this concept, we developed an eco-friendly high-performancethin-layer chromatography (HPTLC) method as an alternative for the conventional HPLC method for the determination of an essential human micronutrient, niacin (NIA), which is used improve the lipid profile of patients. Furthermore, the proposed HPTLC method is capable of determining the structurally related impurities of NIA such as pyridine-2,5-dicarboxylic acid, isonicotinic acid, pyridine, and 5-ethyl-2-methylpyridine, which exhibit nephrotoxic and hepatotoxic effects. The separation of this challenging mixture was achieved on HPTLC sheets using a mixture of ethyl acetate/ethanol/ammonia solution (6:4:0.05, v/v/v), and then the dried plates were scanned at 254 nm. The analytical eco-scale assessment protocol was used to assess the greenness profile of the presented method and compare it with the reported HPLC method. The suggested method was found to be greener with regard to the consumption of solvents and the yielding of waste. The results suggest that the described method can be safely implemented for the routine analysis of NIA pharmaceutical dosage without the interference of potential impurities in quality control laboratories.

Assessment of the Role of Niacin in Managing Cardiovascular Disease Outcomes: A Systematic Review and Meta-analysis.

Importance: Niacin remains a therapeutic option for patients with cardiovascular disease, but recent studies have called into question the effectiveness of other drugs that increase high-density lipoprotein cholesterol levels. Objective: To systematically review and evaluate the evidence supporting current US Food and Drug Administration-approved uses of niacin in cardiovascular disease prevention settings. Data Sources: MEDLINE, Embase, Cochrane Controlled Clinical Trial Register (Central), ClinicalTrials.gov, and TrialResults-center, from database inception to October 2017. Study Selection: The systematic review included clinical trials involving niacin as a treatment for cardiovascular disease. The meta-analysis included randomized clinical trials reporting niacin's effect, as exposure, on at least 1 long-term cardiovascular disease outcome. Data Extraction and Synthesis: Aggregate study-level data were extracted between November 2017 and January 2018 by 3 independent reviewers, and the analysis was performed in February 2018. Inverse-variance weighted methods were used to produce pooled risk ratios using random-effects models for between-study heterogeneity. Random effects-weighted metaregression analysis was used to assess the association of change in high-density lipoprotein cholesterol levels with the log risk ratio of the pooled results. Main Outcomes and Measures: Cardiovascular disease, coronary heart disease mortality, and other cardiovascular events, including acute coronary syndrome, fatal and nonfatal stroke, revascularization, and major adverse cardiac events. Results: Of 119 clinical trials, 17 documented niacin's effect on at least 1 cardiovascular disease outcome. The meta-analysis included 35 760 patients with histories of cardiovascular disease or dyslipidemia. Cumulative evidence found no preventive association of niacin with cardiovascular outcomes in secondary prevention. Stratified meta-analysis showed an association of niacin monotherapy with reduction of some cardiovascular events among patients without statin treatment (acute coronary syndrome: relative risk, 0.74; 95% CI, 0.58-0.96; stroke: relative risk, 0.74; 95% CI, 0.59-0.94; revascularization: relative risk, 0.51; 95% CI, 0.37-0.72). These results were mainly derived from 2 trials conducted in the 1970s and 1980s. Conclusions and Relevance: Niacin may have some use in lipid control for secondary prevention as monotherapy, perhaps in patients intolerant to statins, but evidence is from older studies on a population potentially not representative of current-day patients.

Potential Dietary Contributions From Rice and Wheat Flour Fortification in the Solomon Islands: Results From the 2012-2013 Household Income and Expenditure Survey.

BACKGROUND: Solomon Islands (SI) mandated wheat flour fortification in 2010. Rice is a key staple food in SI, and its fortification may provide an opportunity to deliver additional micronutrients to the population. OBJECTIVE: To determine whether fortified rice (proposed) and fortified wheat flour potentially benefit women of reproductive age (WRA). METHODS: We analyzed data from the 2012-2013 Household Income and Expenditure Survey to quantify food purchases, which served as a proxy for food consumption. We accounted for varied household composition by using adult male equivalent (AME) adjustments. RESULTS: Among 4478 households, 95.6% purchased rice and 86.6% purchased at least 1 food containing fortified wheat flour in the previous 14 days. Median apparent intake of rice among WRA was 205 g/d/AME. If fortified according to proposed standards, this apparent intake could result in the consumption of 12.3 mg iron/d, fulfilling 44% of the estimated average requirement (EAR), and 226 µg folic acid/d, satisfying 57% of World Health Organization's recommended intake of 400 µg/d. Overall, apparent rice consumption could fulfill 113%, 114%, and 131% of the EAR for WRA for zinc, thiamin, and niacin, respectively. Fortified wheat flour was consumed in much lower quantities, with an estimated apparent median intake of 22 g/d/AME among WRA and 78 g/d/AME among women in urban populations. CONCLUSIONS: The potential benefit of fortified wheat flour in SI is likely limited to urban populations. Apparent consumption of fortified rice in SI could contribute considerably to daily intake of iron, B vitamins including folic acid, and zinc among WRA.

Safety assessment of niacin in the US Food and Drug Administration's mini-sentinel system.

PURPOSE: The Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) trial found higher incidence rates of adverse reactions, including bleeding, in patients receiving the combination of extended-release niacin and laropiprant versus placebo. It is not known whether these adverse events are attributable to laropiprant, not approved in the USA, or to extended-release niacin. We compared rates of major gastrointestinal bleeding and intracranial hemorrhage among initiators of extended-release niacin and initiators of fenofibrate. METHODS: We used Mini-Sentinel (now Sentinel) to conduct an observational, new user cohort analysis. We included data from 5 Data Partners covering the period from January 1, 2007 to August 31, 2013. Individuals who initiated extended-release niacin were propensity score-matched to individuals who initiated fenofibrate. Within the matched cohorts, we used Cox proportional hazards models to compare rates of hospitalization for major gastrointestinal bleeding events and intracranial hemorrhage assessed using validated claims-based algorithms. RESULTS: A total of 234 242 eligible extended-release niacin initiators were identified, of whom 210 389 (90%) were 1:1 propensity score-matched to eligible fenofibrate initiators. In propensity score-matched analyses, no differences were observed between exposure groups in rates of major gastrointestinal bleeding (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.82 to 1.18) or intracranial hemorrhage (HR, 1.21; 95% CI, 0.66 to 2.22). Results were similar in pre-specified sensitivity and subgroup analyses. CONCLUSIONS: We did not observe evidence for an association between extended-release niacin versus fenofibrate and rates of major gastrointestinal bleeding or intracranial hemorrhage.

Effect of Combination Cholesterol-Lowering Therapy and Triglyceride-Lowering Therapy on Medical Costs in Patients With Type 2 Diabetes Mellitus.

High triglyceride (TG) levels among patients with type 2 diabetes mellitus (DM) are associated with higher medical costs. We analyzed the economic impact of TG-lowering therapies and whether the association between medical costs and therapy differed according to TG reduction. We conducted an observational cohort study of 184,932 patients with diabetes mellitus who had a TG measurement between January 2012 and June 2013 and a second TG measurement 3 to 15 months later. We identified 4 therapy groups (statin monotherapy, TG-specific monotherapy, statin/TG-specific combination therapy, or no therapy) and stratified those groups by percent change in TG (increased ≥5%, change of ≤4.9%, decreased 5% to 29%, decreased ≥30%). We compared change in medical costs between the year before and after therapy, adjusted for demographic and clinical characteristics. Of the 184,932 total patients, 143,549 (77.6%) received statin monotherapy, 900 (0.5%) received TG-specific monotherapy, 1,956 (1.1%) received statin and TG-specific combination therapy, and 38,527 (20.8%) received no prescription lipid agents. After covariate adjustment, statin/TG-specific agent recipients had a mean 1-year total cost reduction of $1,110. The greatest cost reduction was seen among statin/TG-specific combination therapy patients who reduced TG levels by ≥30% (-$2,859). Statin monotherapy patients who reduced TG by ≥30% also had a large reduction in adjusted costs (-$1,079). In conclusion, we found a substantial economic benefit to treating diabetic patients with statin/TG-specific combination lipid therapy compared with monotherapy of either type or no lipid pharmacotherapy. A TG reduction of ≥30% produced a particularly large reduction in 1-year medical costs.

Lipoprotein(a) in postmenopausal women: assessment of cardiovascular risk and therapeutic options.

INTRODUCTION: Lipoprotein(a) [Lp(a)], a low-density lipoprotein (LDL)-like particle, has been independently associated with increased cardiovascular disease (CVD) risk in various populations, such as postmenopausal women. The purpose of this narrative review is to present current data on the role of Lp(a) in augmenting CVD risk in postmenopausal women and focus on the available therapeutic strategies. METHODS: PubMed was searched for English language publications until November 2015 under the following terms: "therapy" OR "treatment" AND ["lipoprotein (a)" OR "Lp(a)"] AND ("postmenopausal women" OR "menopausal women" OR "menopause"). RESULTS: Only hormone replacement therapy (mainly oral estrogens) and tibolone have been specifically studied in postmenopausal women and can reduce Lp(a) concentrations by up to 44%, although evidence indicating a concomitant reduction in CVD risk associated with Lp(a) is lacking. As alternative treatments for women who cannot, or will not, take hormonal therapies, niacin and the upcoming proprotein convertase subtilisin / kexin type 9 (PCSK-9) inhibitors are effective in reducing Lp(a) concentrations by up to 30%. Statins have minimal or no effect on Lp(a). However, data for these and other promising Lp(a)-lowering therapies including mipomersen, lomitapide, cholesterol-ester-transfer protein inhibitors and eprotirome are derived from studies in the general, mainly high CVD risk, population, and include only subpopulations of postmenopausal women. CONCLUSIONS: Past, present and emerging therapies can reduce Lp(a) concentrations to a varying extent. Overall, it remains to be proven whether the aforementioned reductions in Lp(a) by these therapeutic options are translated into CVD risk reduction in postmenopausal women.

Effects of Vascular and Nonvascular Adverse Events and of Extended-Release Niacin With Laropiprant on Health and Healthcare Costs.

BACKGROUND: Extended-release niacin with laropiprant did not significantly reduce the risk of major vascular events and increased the risk of serious adverse events in Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE), but its net effects on health and healthcare costs are unknown. METHODS AND RESULTS: 25 673 participants aged 50 to 80 years with previous cardiovascular disease were randomized to 2 g of extended-release niacin with 40 mg of laropiprant daily versus matching placebo, in addition to effective statin-based low-density lipoprotein cholesterol-lowering treatment. The net effects of niacin-laropiprant on quality-adjusted life years and hospital care costs (2012 UK £; converted into US $ using purchasing power parity index) during 4 years in HPS2-THRIVE were evaluated using estimates of the impact of serious adverse events on health-related quality of life and hospital care costs. During the study, participants assigned niacin-laropiprant experienced marginally but not statistically significantly lower survival (0.012 fewer years [standard error (SE) 0.007]), fewer quality-adjusted life years (0.023 [SE 0.007] fewer using UK EQ-5D scores; 0.020 [SE 0.006] fewer using US EQ-5D scores) and accrued greater hospital costs (UK £101 [SE £37]; US $145 [SE $53]). Stroke, heart failure, musculoskeletal events, gastrointestinal events, and infections were associated with significant decreases in health-related quality of life in both the year of the event and in subsequent years. All serious vascular and nonvascular events were associated with substantial increases in hospital care costs. CONCLUSIONS: In HPS2-THRIVE, the addition of extended-release niacin-laropiprant to statin-based therapy reduced quality of life-adjusted survival and increased hospital costs. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT00461630.

The assessment of the effect of a cosmetic product brightening the skin of people with discolorations of different etiology.

BACKGROUND: Hyperpigmentations are disorders displayed with a change in the color of the skin, its strange shape, the lack of symmetry, and irregular placement. They appear no matter on the age, gender, and often as a congenital defect. Disorder connected with overproduction of melanin by pigmentary cells. The change of color is due to endogenous and exogenous cause. OBJECTIVES: The aim of this thesis was to conduct a research in vivo. This will allow to judge the effectiveness of the cosmetic product which brightens the skin with hyperpigmentation problems. The characteristics of dermocosmetics were tested on people with various etiology of hyperpigmentation. The aim of the research was to assess the effect of the active substances used daily on skin hyperpigmentation. METHODS: The tests were carried out on groups of patients with hyperpigmentations. The application of the pharmaceutical and the use of specific apparatus measurements were taken on every medical checkup. A survey was conducted to assess the changes in the face, neck, and neckline skin. The research was based on the apparatus analysis of the skin condition (MPA® , VISIA® ). RESULTS: Regular application of the pharmaceutical caused brightening of hyperpigmentations (P < 0.05). General improvement in skin condition was also observed - the increase in skin elasticity, smoothness, and the enhancement of hydration levels. CONCLUSIONS: Dermocosmetics for people with hyperpigmentation are an essential part of their medical treatment. In case of epidermal hyperpigmentation, the recipe of individually chosen and tested combination of ingredients enables us to reach satisfactory results.

Nicotinic acid treatment for Paralepistopsis acromelalga intoxication: assessment using magnetic resonance imaging.

CONTEXT: Paralepistopsis acromelalga, formerly known as Clitocybe acromelalga, is a rare poisonous mushroom. The mycotoxins in this mushroom cause symptoms resembling those of erythromelalgia; however, its pathogenesis remains unclear. In this report, a patient who received nicotinic acid treatment for P. acromelalga poisoning and radiological evaluation for erythromelalgia has been presented. Case detail: A 59-year-old woman was hospitalized for redness, swelling, and burning pain in her extremities that rendered difficulty in walking, and a diagnosis of P. acromelalga poisoning was made by detailed interview and mushroom identification. She was treated with intravenous nicotinic acid for 17 days followed by oral nicotinic acid amide for 2 months. She exhibited rapid symptomatic improvement and walked independently after 11 days of initial treatment. Initial MRI of her feet revealed toe-dominated subcutaneous thickening. After nicotinic acid treatment, those radiological findings improved dramatically. DISCUSSION: The subcutaneous thickening evident on MRI indicated P. acromelalga poisoning-induced erythromelalgia involved subcutaneous inflammatory edema. The typical duration of edema without treatment is more than a month. The improvement on MRI after nicotinic acid treatment indicated that the adequate vasodilation induced by nicotinic acid contributed to resolution of the symptoms. Nicotinic acid was associated with the improvement of the edematous changes caused by the P. acromelalga intoxication.

An analysis of the meal pattern at the nutrient level in Polish women.

BACKGROUND: Before the 1990's, access to a variety of foods in Eastern Europe was limited, which could have influenced the currently analyzed dietary behaviors pertaining to overweight and obesity development. The aim of this study was to describe the daily profile of meal patterns in Polish women aged 50-70 at the nutrient level. METHODS: The anthropometrical parameters of four-hundred and fifty Polish women aged 50-70 were assessed. Three 24-hour dietary recalls and validated questionnaires regarding socio-demographic-economic status and meal frequency were applied. Timing in food intake was considered as follow: 6:00-8:59 CET - breakfast, 9:00-11:59 CET - morning snacks, 12:00-14:59 CET - lunch, 15:00-17:59 CET - afternoon snacks, 18:00-21:00 CET - dinner. Statistical analyses were conducted using Tukey's multiple comparison tests and discriminant analysis. RESULTS: No statistically significant differences were found in socio-demographic-economic and anthropometrical characteristics between women categorized to differentiated meal frequency intakes. However, the subjects from the 5-meal-per-day group were characterized by higher anthropometrical parameters, the statistically lowest percentage of regularity in meal consumption and skipping meals related to shortest breaks between meals. At the nutrient level, potassium, niacin, vitamin E and vitamin D were selected in the discriminant analysis as the nutrients most strongly related to different dietary behaviors. CONCLUSIONS: Our findings did not provide sufficient evidence that diverse nutrient intake could lead to the development of a specific nutritional profile in Polish women.

Dose-response-time modelling: Second-generation turnover model with integral feedback control.

This study presents a dose-response-time (DRT) analysis based on a large preclinical biomarker dataset on the interaction between nicotinic acid (NiAc) and free fatty acids (FFA). Data were collected from studies that examined different rates, routes, and modes of NiAc provocations on the FFA time course. All information regarding the exposure to NiAc was excluded in order to demonstrate the utility of a DRT model. Special emphasis was placed on the selection process of the biophase model. An inhibitory Imax-model, driven by the biophase amount, acted on the turnover rate of FFA. A second generation NiAc/FFA model, which encompasses integral (slow buildup of tolerance - an extension of the previously used NiAc/FFA turnover models) and moderator (rapid and oscillatory) feedback control, was simultaneously fitted to all time courses in normal rats. The integral feedback control managed to capture an observed 90% adaptation (i.e., almost a full return to baseline) when 10 days constant-rate infusion protocols of NiAc were used. The half-life of the adaptation process had a 90% prediction interval between 3.5-12 in the present population. The pharmacodynamic parameter estimates were highly consistent when compared to an exposure-driven analysis, partly validating the DRT modelling approach and suggesting the potential of DRT analysis in areas where exposure data are not attainable. Finally, new numerical algorithms, which rely on sensitivity equations to robustly and efficiently compute the gradients in the parameter optimization, were successfully used for the mixed-effects approach in the parameter estimation.