Formaldehyde in "nontoxic" Nail Polish

Background: Nail polish is known to contain potentially hazardous chemicals that have been linked to adverse health effects after overexposure. Formaldehyde is used as an antimicrobial, preservative, and nail hardener in select nail products, yet it is a recognized carcinogen and potent allergen in allergic contact dermatitis. Objective: The aim of this study was to investigate whether formaldehyde is present in nail polishes marketed as formaldehyde-free. Methods: Twenty-nine cosmetic nail polishes were purchased for analysis; of these, 28 were advertised as formaldehyde-free and/or did not declare formaldehyde in their ingredient lists. Initial testing was pursued using the chromotropic acid method, which uses a red-purple color change to indicate the presence of formaldehyde. Products were subsequently analyzed at least twice using high-performance liquid chromatography, quantifying formaldehyde amount above the detection limit of 2 ppm. Conclusions: High-performance liquid chromatography analysis found 5 of 29 products containing formaldehyde, 4 of which were advertised as formaldehyde-free. All other products were negative for formaldehyde (<2 ppm). Further investigation is warranted among brands testing positive and whether multiple products within the same line contain formaldehyde. Nail products must be labeled appropriately to avoid adverse reactions among individuals with cutaneous sensitivities

Patch Testing With Carmine 2.5% in Petrolatum by the North American Contact Dermatitis Group, 2011-2012

BACKGROUND: Carmine is a natural red dye that may cause allergic contact dermatitis. OBJECTIVE: The aim of this study was to analyze patch test reactions to carmine (2.5% in petrolatum) and characterize carmine-positive patients. METHODS: This study conducted a retrospective analysis of North American Contact Dermatitis Group data compiled between 2011 and 2012. RESULTS: Of 4240 patients patch tested to carmine, 132 (3.1%) had reactions with a final interpretation of allergic (positive). Carmine-positive patients were significantly more likely to be female (77.7% vs 68.3%; P = 0.0237) and have a final primary diagnosis of allergic contact dermatitis (74.8% vs 47.2%; P \u3c 0.0001). As compared with carmine-negative patients, carmine-positive patients were significantly more likely to have involvement of all facial sites combined (48.1% vs 29.9%; P \u3c 0.0001) and the lips (7.6% vs 3.6%; P = 0.0166). At final reading, most carmine reactions were weak (+; 64.9%). Approximately half (53.4%) were currently clinically relevant; identified sources were primarily personal care products (77.1%), especially makeup (31.4%) and lip products (8.6%). CONCLUSIONS: Weak patch test reactions to carmine should be interpreted with caution. Allergic contact dermatitis to carmine should be suspected in women with facial and/or lip dermatitis, especially those using carmine-containing cosmetics

Contact Dermatitis Associated With Nail Care Products: Retrospective Analysis of North American Contact Dermatitis Group Data, 2001-2016

BACKGROUND: Ingredients in nail care products may lead to allergic and/or irritant contact dermatitis. OBJECTIVE: The aims of this study were to determine frequency of contact dermatitis associated with nail care products, characterize associated body sites, and describe causative allergens. METHODS: A retrospective analysis was conducted with the North American Contact Dermatitis Group data between 2001 and 2016. RESULTS: Of the 38,775 patients tested, 769 (2.0%) had: 1) more than 1 allergic patch test reaction associated with a nail care product (n = 746), 2) irritant contact dermatitis associated with a nail care product (n = 14), or 3) both (n = 9). Primary body sites included the face (43.0%) and hands (27.6%). The top 5 allergens were (2-hydroxyethyl methacrylate (273/482, 56.6%), methyl methacrylate (210/755, 27.8%), ethyl acrylate (190/755, 25.2%), ethyl-2-cyanoacrylate (12/175, 6.9%) and tosylamide (273/755, 36.2%). Frequency of allergy to 2-hydroxyethyl methacrylate (P = 0.0069) and ethyl acrylate (P = 0.0024) significantly increased over the study period, whereas allergy secondary to tosylamide significantly decreased (P \u3c 0.0001). CONCLUSIONS: As long-lasting nail techniques become widespread, the prevalence of contact dermatitis to nail care products is expected to increase. Almost one-fifth of nail care product-associated allergens would have been missed without additional screening allergens beyond the North American Contact Dermatitis Group series, underscoring the need for testing to a broad array of allergens

Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol

Background: Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. Objectives: In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. Methods: ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was 13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with Pinteraction = 0.43. Conclusions: In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402

Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial

Background: After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1·4–1·8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes. Methods: ODYSSEY OUTCOMES was a randomised, double-blind, placebo-controlled trial, done at 1315 sites in 57 countries, that compared alirocumab with placebo in patients who had been admitted to hospital with an acute coronary syndrome (myocardial infarction or unstable angina) 1–12 months before randomisation and who had raised concentrations of atherogenic lipoproteins despite use of high-intensity statins. Patients were randomly assigned (1:1) to receive alirocumab or placebo every 2 weeks; randomisation was stratified by country and was done centrally with an interactive voice-response or web-response system. Alirocumab was titrated to target LDL cholesterol concentrations of 0·65–1·30 mmol/L. In this prespecified analysis, we investigated the effect of alirocumab on cardiovascular events by glycaemic status at baseline (diabetes, prediabetes, or normoglycaemia)—defined on the basis of patient history, review of medical records, or baseline HbA1c or fasting serum glucose—and risk of new-onset diabetes among those without diabetes at baseline. The primary endpoint was a composite of death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. ODYSSEY OUTCOMES is registered with ClinicalTrials.gov, number NCT01663402. Findings: At study baseline, 5444 patients (28·8%) had diabetes, 8246 (43·6%) had prediabetes, and 5234 (27·7%) had normoglycaemia. There were no significant differences across glycaemic categories in median LDL cholesterol at baseline (2·20–2·28 mmol/L), after 4 months' treatment with alirocumab (0·80 mmol/L), or after 4 months' treatment with placebo (2·25–2·28 mmol/L). In the placebo group, the incidence of the primary endpoint over a median of 2·8 years was greater in patients with diabetes (16·4%) than in those with prediabetes (9·2%) or normoglycaemia (8·5%); hazard ratio (HR) for diabetes versus normoglycaemia 2·09 (95% CI 1·78–2·46, p<0·0001) and for diabetes versus prediabetes 1·90 (1·65–2·17, p<0·0001). Alirocumab resulted in similar relative reductions in the incidence of the primary endpoint in each glycaemic category, but a greater absolute reduction in the incidence of the primary endpoint in patients with diabetes (2·3%, 95% CI 0·4 to 4·2) than in those with prediabetes (1·2%, 0·0 to 2·4) or normoglycaemia (1·2%, −0·3 to 2·7; absolute risk reduction pinteraction=0·0019). Among patients without diabetes at baseline, 676 (10·1%) developed diabetes in the placebo group, compared with 648 (9·6%) in the alirocumab group; alirocumab did not increase the risk of new-onset diabetes (HR 1·00, 95% CI 0·89–1·11). HRs were 0·97 (95% CI 0·87–1·09) for patients with prediabetes and 1·30 (95% CI 0·93–1·81) for those with normoglycaemia (pinteraction=0·11). Interpretation: After a recent acute coronary syndrome, alirocumab treatment targeting an LDL cholesterol concentration of 0·65–1·30 mmol/L produced about twice the absolute reduction in cardiovascular events among patients with diabetes as in those without diabetes. Alirocumab treatment did not increase the risk of new-onset diabetes. Funding: Sanofi and Regeneron Pharmaceuticals