Obesity Reduction Within a Generation: The Dual Roles of Prevention and Treatment

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93699/1/oby.2011.199.pd

Are post-treatment low-density lipoprotein subclass pattern analyses potentially misleading?

<p>Abstract</p> <p>Background</p> <p>Some patients administered cholesterol-lowering therapies may experience an increase in the proportion of small LDL particles, which may be misinterpreted as a worsening of atherosclerotic coronary heart disease risk. This study assessed the lipid effects of adding ezetimibe to atorvastatin or doubling the atorvastatin dose on low-density lipoprotein cholesterol (LDL-C) levels (and the cholesterol content of LDL subclasses), LDL particle number (approximated by apolipoprotein B), and LDL particle size. This was a multicenter, double-blind, randomized, parallel-group study of hypercholesterolemic, high atherosclerotic coronary heart disease risk patients. After stabilization of atorvastatin 40 mg, 579 patients with LDL-C >70 mg/dL were randomized to 6 weeks of ezetimibe + atorvastatin 40 mg or atorvastatin 80 mg. Efficacy parameters included changes from baseline in LDL-C, apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), and lipoprotein subclasses (Vertical Auto Profile II) and pattern for the overall population, as well as patient subgroups with baseline triglyceride levels <150 mg/dL or ≥150 mg/dL.</p> <p>Results</p> <p>Both treatments significantly reduced LDL-C (and the cholesterol content of most LDL subfractions [LDL_1-4]) apolipoprotein B, non-HDL-C levels, but did not reduce the proportion of smaller, more dense LDL particles; in fact, the proportion of Pattern B was numerically increased. Results were generally similar in patients with triglyceride levels <150 or ≥150 mg/dL.</p> <p>Conclusions</p> <p>When assessing the effects of escalating cholesterol-lowering therapy, effects upon Pattern B alone to assess coronary heart disease risk may be misleading when interpreted without considerations of other lipid effects, such as reductions in LDL-C, atherogenic lipoprotein particle concentration, and non-HDL-C levels.</p> <p>Trial Registration</p> <p>(Registered at clinicaltrials.gov: Clinical trial # NCT00276484)</p

Safety profile of statins alone or combined with ezetimibe : a pooled analysis of 27 studies including over 22,000 patients treated for 6-24 weeks

Aims:  The aim of this analysis was to assess the overall safety and tolerability profiles of various statins + ezetimibe vs. statin monotherapy and to explore tolerability in sub-populations grouped by age, race, and sex. Methods:  Study-level data were combined from 27 double-blind, placebo-controlled or active-comparator trials that randomized adult hypercholesterolemic patients to statin or statin + ezetimibe for 6-24 weeks. In the full cohort, % patients with AEs within treatment groups (statin: N = 10,517; statin + ezetimibe: N = 11,714) was assessed by logistic regression with terms for first-/second-line therapy (first line = drug-naïve or rendered drug-naïve by washout at study entry; second line = ongoing statin at study entry or statin run-in), trial within first-/second-line therapy, and treatment. The same model was fitted for age (< 65, ≥ 65 years), sex, race (white, black, other) and first-/second-line subgroups with additional terms for subgroup and subgroup-by-treatment interaction. Results:  In the full cohort, the only significant difference between treatments was consecutive AST or ALT elevations ≥ 3 × upper limit of normal (ULN) (statin: 0.35%, statin + ezetimibe: 0.56%; p = 0.017). Significantly more subjects reported ≥ 1 AE; drug-related, hepatitis-related and gastrointestinal-related AEs; and CK elevations ≥ 10 × ULN (all p ≤ 0.008) in first-line vs. second-line therapy studies with both treatments. AEs were generally similar between treatments in subgroups, and similar rates of AEs were reported within age and race subgroups; however, women reported generally higher AE rates. Conclusions:  In conclusion, in second-line studies, ongoing statin treatment at study entry likely screened out participants for previous statin-related AEs and tolerability issues. These results describe the safety profiles of widely used lipid-lowering therapies and encourage their appropriate and judicious use in certain subpopulations

The effect of gefapixant, a P2X3 antagonist, on cough reflex sensitivity: A randomised placebo-controlled study

We evaluated the effect of gefapixant on cough reflex sensitivity to evoked tussive challenge.In this phase 2, double-blind, two-period study, patients with chronic cough (CC) and healthy volunteers (HV) were randomised to single-dose gefapixant 100 mg or placebo in a crossover fashion. Sequential inhalational challenges with ATP, citric acid, capsaicin and distilled water were performed 1, 3 and 5 h after dosing. Mean concentrations evoking ≥2 coughs (C2) and ≥5 coughs (C5) post dose versus baseline were co-primary endpoints. Objective cough frequency (coughs·h−1) over 24 h and a cough severity visual analogue scale (VAS) were assessed in CC patients. Adverse events were monitored.24 CC patients and 12 HV were randomised (mean age 61 and 38 years, respectively). The cough challenge threshold increased for ATP by 4.7-fold (C2, p≤0.001) and 3.7-fold (C5, p=0.007) for gefapixant versus placebo in CC patients; in HV, C2 and C5 increased 2.4-fold (C2, p=0.113; C5, p=0.003). The distilled water C2 and C5 thresholds increased significantly (

Effect on Fasting Serum Glucose Levels of Adding Ezetimibe to Statins in Patients With Nondiabetic Hypercholesterolemia

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Persistence of lipoatrophy after a four-year long interruption of antiretroviral therapy for HIV1 infection: case report

BACKGROUND: HIV-infected patients on long-term highly active antiretroviral therapy often present peculiar patterns of fat redistribution, referred to as lipodystrophy. In spite of recent investigations, it is not known whether and to what extent the main features of lipodystrophy – that is lipoatrophy of peripheral fat at face, limbs and buttocks, as well as fat accumulation at breasts, abdomen and the dorso-cervical region – can be reversible once clinically manifest. CASE PRESENTATION: A 35 year old Caucasian HIV infected female developed severe diffuse lipodystrophy while on highly active antiretroviral therapy. A remarkable increase of breast size, fat accumulation at waist, and a fat pad on her lumbar spine were paralleled by progressive and disfiguring lipoatrophy of face, limbs and buttocks. The patient decided to interrupt her therapy after 20 months, with a stably suppressed viremia and a CD4 lymphocyte count >500/μL. She could carry on a safe treatment interruption for longer than 4 years. Most sites of fat accumulation switched to nearly normal appearance, whereas lipoatrophy was substantially unchanged at all affected sites. CONCLUSION: our observation provides pictorial evidence that lipoatrophy may not be reversible even under ideal circumstances. Therefore, strategies to prevent lipoatrophy should be considered when defining therapeutic regimens for HIV infected patients, especially those at high risk

Obesity and its association with diets and sedentary life style among school children in Seoul, Korea: Compliance with Dietary References Intakes for Koreans food guides

This study compared obese children's food group intakes with the new Dietary References Intakes for Koreans (KDRIs) food guides for 5th-6th grade school children. This study also determined the extent of sedentary life styles related with obesity in this area of children. This is a cross-sectional study of 799 school children. The dietitian sent a survey form describing the project and a questionnaire to the subject's family. The questionnaire included child demographics, family history of chronic diseases, the daily servings of five food groups, such as grains, meat and beans, dairy products, fruits, and vegetables. The daily or weekly hours of physical activity, television viewing, and computer usage were also surveyed. Obesity index (%) of the subjects was calculated, and children with an obesity index (%) equal to or greater than 20 were classified as the obese. Among the 799 participants, 50.7% were female. The percentages of the normal and the obese were 691 (86.5%) and 108 (13.5%) respectively. Obese children reported eating less vegetables (p<0.05), more high sugar snacks (p<0.05), and high fat snacks (p<0.05) than normal children. No significant differences in food servings of grains, meats and beans, and fruits, and dairy products between the normal and the obese were shown. Obese children reported fewer hours of physical activities (p<0.05) and more hours of computer usage (p<0.05) than normal children. Girls showed less likelihood of being obese (odds ratio, 0.575, CI (0.38, 0.87), p<0.05). More hours of physical activity significantly decreased the likelihood of being obese (odds ratio, 0.572, CI (0.35, 0.92), p<0.05). Family history of obesity almost doubled the likelihood of obesity in children (odds ratio, 2.653, CI (1.660, 4.241), p<0.05). In conclusion, frequent snacking, inadequate vegetable consumption, and sedentary lifestyle increased significantly the likelihood of obesity in children, which suggest that obesity intervention in this age group should focuse more on those variables