Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Hypohydrotic ectodermal dysplasia: an unusual presentation and management in an 11-year-old Xhosa boy.

Ectodermal dysplasia (ED) is an inherited disorder in which two or more ectodermally derived structures fail to develop, or are abnormal in development. Hypohydrotic ectodermal dysplasia (HED) or Christ-Siemens-Touraine syndrome, is an X-linked recessive syndrome with an incidence of 1/10,000 to 1/100,000 births. Because of its X-linked inheritance pattern, it is more common in males. HED is characterised by hypohydrosis (diminished perspiration), hypotrichosis (decreased amount of hair) and microdontia (small teeth), hypodontia (lack of development of one or more teeth) or adontia (total lack of tooth development). These patients present diagnostic and treatment challenges because of variable oral manifestations. This report describes an 11-year-old Xhosa boy, who was referred to the University Dental Faculty by his general medical practitioner because of hypodontia. General facial features included: frontal bossing, a depressed nasal bridge, 'butterfly' pattern of eczema over the nasal bridge to the malar process of each cheek, thinned out hair, loss of vertical dimension of face and dry skin. Intra-oral examination revealed hypodontia with peg-shaped anterior teeth and diastemas. Radiological examination revealed no developing permanent teeth or tooth buds. Diagnosis was confirmed by doing a sweat gland count. Management included oral hygiene instruction, fluoride treatments, construction of a partial lower denture and counselling about his condition with particular reference to the danger of hyperthermia and control of allergies.Articl

Hypohydrotic ectodermal dysplasia: an unusual presentation and management in an 11-year-old Xhosa boy.

Ectodermal dysplasia (ED) is an inherited disorder in which two or more ectodermally derived structures fail to develop, or are abnormal in development. Hypohydrotic ectodermal dysplasia (HED) or Christ-Siemens-Touraine syndrome, is an X-linked recessive syndrome with an incidence of 1/10,000 to 1/100,000 births. Because of its X-linked inheritance pattern, it is more common in males. HED is characterised by hypohydrosis (diminished perspiration), hypotrichosis (decreased amount of hair) and microdontia (small teeth), hypodontia (lack of development of one or more teeth) or adontia (total lack of tooth development). These patients present diagnostic and treatment challenges because of variable oral manifestations. This report describes an 11-year-old Xhosa boy, who was referred to the University Dental Faculty by his general medical practitioner because of hypodontia. General facial features included: frontal bossing, a depressed nasal bridge, 'butterfly' pattern of eczema over the nasal bridge to the malar process of each cheek, thinned out hair, loss of vertical dimension of face and dry skin. Intra-oral examination revealed hypodontia with peg-shaped anterior teeth and diastemas. Radiological examination revealed no developing permanent teeth or tooth buds. Diagnosis was confirmed by doing a sweat gland count. Management included oral hygiene instruction, fluoride treatments, construction of a partial lower denture and counselling about his condition with particular reference to the danger of hyperthermia and control of allergies.Articl

Modeling the fate of glucosinolates during thermal processing of Brassica vegetables

Glucosinolates are secondary metabolites of Brassicavegetables that have been associated with health benefits. The concentrations of these compounds are strongly affected by processing of the vegetables. Various mechanisms are responsible for these changes: Lysis of plant cells and compartments, diffusion and leaching of glucosinolates and myrosinase (a plant enzyme able to hydrolyze glucosinolates) into the cooking water, enzymatic hydrolysis of glucosinolates, inactivation of myrosinase and thermal degradation of glucosinolates. This publication presents a dynamic mathematical model that includes these mechanisms with their estimated parameters and the effect of temperature on them. Simulations made by the model for several process conditions show losses of glucosinolates as a consequence of domestic boiling of 69%, microwaving of 8%, industrial blanching of 37% and by industrial sterilization of 82%. The model can assist in adapting the processing conditions like the time–temperature profile and the vegetable–water ratio to optimize industrial and domestic processing of Brassicavegetables in terms of health benefits. In addition this model can help to add the effect of vegetable preparation practices on the quantitative glucosinolate intake in epidemiological studies

Attitudes to water fluoridation in South Africa 1998 � Part II: influence of educational, income and occupational levels

TandheelkundeGemeenskapstandheelkundePlease help us populate SUNScholar with the post print version of this article. It can be e-mailed to: [email protected]

Attitudes to water fluoridation in South Africa 1998. Part II. Influence of educational and occupational levels.

The purpose of this report is to investigate the influence of education, income and occupation on public perceptions of water fluoridation (WF). A questionnaire on current knowledge, sources of information, the purpose of WF and its desirability was administered to a representative sample of 2,220 individuals over the age of 18 years. Knowledge of WF increased with educational level (range from 13.5% in the grade 0-5 group to 59% in the grade 12 plus group). Lack of knowledge decreased from 76% to 37% in these groups respectively. Knowledge levels varied from 19% to 68% across the occupational spectrum and from 13% to 88% across the income spectrum. In educational levels up to grade 12, electronic media were most frequently cited as dominant sources of information among 40-50% of respondents, whereas in the grade 12 plus group print media (37%) dominated. Sources of knowledge on fluoridation were largely obtained from print and electronic media for both categories. Only 28% in the educational level up to grade 5 thought the purpose of WF was to protect teeth against decay. This gradually increased to 55% in the grade 12 plus category. More than a quarter of the population in both the occupational and income categories indicated that the purpose of WF was to purify water and protect teeth from decay. The number of respondents who thought that water should be fluoridated increased with level of education from 58% to 70%, while those who disagreed decreased as qualifications increased. The lower- and middle-income groups were more supportive of WF than the very-high-income groups. Persons in high administrative professional and executive positions were more opposed (27%) to WF than semi-skilled and unskilled workers (5%).Articl

One-year evaluation of atraumatic resorative treatment and minimum intervention techniques on primary teeth.

TandheelkundeGemeenskapstandheelkundePlease help us populate SUNScholar with the post print version of this article. It can be e-mailed to: [email protected]

Comparison of the degradation and leaching kinetics of glucosinolates during processing of four Brassicaceae (broccoli, red cabbage, white cabbage, Brussels sprouts)

Glucosinolates (GSs) are secondary metabolites of Brassica vegetables that are associated with health benefits. The concentrations of these compounds are strongly affected by processing of the vegetables. During thermal treatment of Brassicaceae, such as domestic cooking, different mechanisms affecting the content of GSs can take place and were modeled in the present study: Lysis of plant cells and compartments, leaching of GSs into the cooking water and thermal degradation of GSs in both the intact vegetable tissue and the cooking water. These mechanisms were described mathematically and the model parameters for broccoli, Brussels sprouts, red cabbage and white cabbage were estimated based on experimental results. Differences between the thermostability of the same GSs originating from different Brassicaceae could be detected, as well as differences between the thermostability of the same GSs in the vegetable matrix compared to that in the cooking water. Industrial relevance: This mathematical model and the estimated parameters can be used to simulate the different glucosinolate contents in prepared foods considering the processing method. This will be a very useful tool for food research and industry to make predictions about the nutritional quality of foods and to optimize their health related quality attributes