Don P. Wilson

National Lipid Association recommendations for patient-centered management of dyslipidemia: Part 1 - executive summary *

Various organizations and agencies have issued recommendations for the management of dyslipidemia. Although many commonalities exist among them, material differences are present as well. The leadership of the National Lipid Association (NLA) convened an Expert Panel to develop a consensus set of recommendations for patient-centered management of dyslipidemia in clinical medicine. The current Executive Summary highlights the major conclusions in Part 1 of the recommendations report of the NLA Expert Panel and includes: (1) background and conceptual framework for formulation of the NLA Expert Panel recommendations; (2) screening and classification of lipoprotein lipid levels in adults; (3) targets for intervention in dyslipidemia management; (4) atherosclerotic cardiovascular disease risk assessment and treatment goals based on risk category; (5) atherogenic cholesterol-non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol-as the primary targets of therapy; and (6) lifestyle and drug therapies intended to reduce morbidity and mortality associated with dyslipidemia.

National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia: Part 2

An Expert Panel convened by the National Lipid Association previously developed a consensus set of recommendations for the patient-centered management of dyslipidemia in clinical medicine (part 1). These were guided by the principle that reducing elevated levels of atherogenic cholesterol (non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol) reduces the risk for atherosclerotic cardiovascular disease. This document represents a continuation of the National Lipid Association recommendations developed by a diverse panel of experts who examined the evidence base and provided recommendations regarding the following topics: (1) lifestyle therapies; (2) groups with special considerations, including children and adolescents, women, older patients, certain ethnic and racial groups, patients infected with human immunodeficiency virus, patients with rheumatoid arthritis, and patients with residual risk despite statin and lifestyle therapies; and (3) strategies to improve patient outcomes by increasing adherence and using team-based collaborative care.

National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia: Part 1—Full Report

The leadership of the National Lipid Association convened an Expert Panel to develop a consensus set of recommendations for patient-centered management of dyslipidemia in clinical medicine. An Executive Summary of those recommendations was previously published. This document provides support for the recommendations outlined in the Executive Summary. The major conclusions include (1) an elevated level of cholesterol carried by circulating apolipoprotein B-containing lipoproteins (non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol [LDL-C], termed atherogenic cholesterol) is a root cause of atherosclerosis, the key underlying process contributing to most clinical atherosclerotic cardiovascular disease (ASCVD) events; (2) reducing elevated levels of atherogenic cholesterol will lower ASCVD risk in proportion to the extent that atherogenic cholesterol is reduced. This benefit is presumed to result from atherogenic cholesterol lowering through multiple modalities, including lifestyle and drug therapies; (3) the intensity of risk-reduction therapy should generally be adjusted to the patients absolute risk for an ASCVD event; (4) atherosclerosis is a process that often begins early in life and progresses for decades before resulting a clinical ASCVD event. Therefore, both intermediate-term and long-term or lifetime risk should be considered when assessing the potential benefits and hazards of risk-reduction therapies; (5) for patients in whom lipid-lowering drug therapy is indicated, statin treatment is the primary modality for reducing ASCVD risk; (6) nonlipid ASCVD risk factors should also be managed appropriately, particularly high blood pressure, cigarette smoking, and diabetes mellitus; and (7) the measurement and monitoring of atherogenic cholesterol levels remain an important part of a comprehensive ASCVD prevention strategy.

The PedsQL™ Multidimensional Fatigue Scale in pediatric obesity: Feasibility, reliability and validity

OBJECTIVE The PedsQL (Pediatric Quality of Life Inventory) is a modular instrument designed to measure health-related quality of life (HRQOL) and disease-specific symptoms in children and adolescents. The PedsQL Multidimensional Fatigue Scale was designed as a child self-report and parent proxy-report generic symptom-specific instrument to measure fatigue in pediatric patients. The objective of the present study was to determine the feasibility, reliability, and validity of the PedsQL Multidimensional Fatigue Scale in pediatric obesity. METHODS The 18-item PedsQL Multidimensional Fatigue Scale (General Fatigue, Sleep/Rest Fatigue, and Cognitive Fatigue domains) and the PedsQL 4.0 Generic Core Scales were completed by 41 pediatric patients with a physician-diagnosis of obesity and 43 parents from a hospital-based Pediatric Endocrinology Clinic. RESULTS The PedsQL Multidimensional Fatigue Scale evidenced minimal missing responses (1.6%, child report; 0.5%, parent report), achieved excellent reliability for the Total Fatigue Scale Score (alpha = 0.90 child report, 0.90 parent report), distinguished between pediatric patients with obesity and healthy children, and was significantly correlated with the PedsQL 4.0 Generic Core Scales supporting construct validity. Pediatric patients with obesity experienced fatigue comparable with pediatric patients receiving cancer treatment, demonstrating the relative severity of their fatigue symptoms. CONCLUSIONS The results demonstrate the measurement properties of the PedsQL Multidimensional Fatigue Scale in pediatric obesity. The findings suggest that the PedsQL Multidimensional Fatigue Scale may be utilized in the standardized evaluation of fatigue in pediatric patients with obesity.

The PedsQL™ Multidimensional Fatigue Scale in type 1 diabetes: feasibility, reliability, and validity

Background: The Pediatric Quality of Life Inventory (PedsQL™, Mapi Research Trust, Lyon, France; www.pedsql.org) is a modular instrument designed to measure health‐related quality of life and disease‐specific symptoms in children and adolescents. The PedsQL Multidimensional Fatigue Scale was designed as a child self‐report and parent proxy‐report generic symptom‐specific instrument to measure fatigue in pediatric patients. The objective of the present study was to determine the feasibility, reliability, and validity of the PedsQL Multidimensional Fatigue Scale in type 1 diabetes.

Compliance with blood glucose monitoring in children with type 1 diabetes mellitus.

Compliance with blood glucose monitoring was studied in 18 children with type 1 diabetes. Using specially equipped blood glucose reflectance meters, children monitored their blood glucose levels, with and without knowledge of the meters memory capability. Poor compliance, as exhibited by fabricated test results (40%) and failure to record test results (18%), occurred in a significant proportion of children. Further research is needed to explore reasons for such behavior and to suggest strategies for improving compliance.

The ePedsQL™ in Type 1 and Type 2 Diabetes: Feasibility, Reliability and Validity of the Pediatric Quality of Life Inventory™ Internet Administration

OBJECTIVE—The Pediatric Quality of Life Inventory (PedsQL) is a modular instrument designed to measure health-related quality of life (HRQOL) in children and adolescents aged 2–18 years. The PedsQL 4.0 Generic Core Scales are child self-report and parent proxy–report scales developed as the generic core measure to be integrated with the PedsQL disease-specific modules. The electronic version of the PedsQL 4.0 (ePedsQL) was designed for Internet administration. RESEARCH DESIGN AND METHODS—Utilizing a randomized crossover design, the PedsQL scales were administered to 92 pediatric patients with type 1 or type 2 diabetes and 93 parents in electronic and paper formats. RESULTS—Missing values (0.76% child report, 0.37% parent report), internal consistency reliability (total scale score α = 0.90 child report, 0.92 parent report), and mean scores (total scale score M = 78.41 child report, 76.19 parent report) were equivalent between the electronic and paper-and-pencil modes of administration. The ePedsQL distinguished between healthy children and children with diabetes. CONCLUSIONS—The ePedsQL Internet mode of administration demonstrated equivalent measurement properties to the well-established PedsQL paper-and-pencil mode of administration.

Improved Glycemic Control After Supervised 8-wk Exercise Program in Insulin-Dependent Diabetic Adolescents

Eight insulin-dependent adolescents (4 boys, 4 girls) participated in an 8-wk program of supervised exercise, and 8 matched controls were encouraged to exercise on their own without supervision. All 16 subjects were asked to follow a standard ADA diet plan, kept a self-reported log of caloric intake, and met with a dietitian weekly to review their diets. Exercise for the supervised subjects was scheduled between the routine afternoon snack and the evening meal, and subjects were asked not to consume additional food on exercise days. After the 8-wk program, glycemic control, as measured by glycosylated serum albumin and blood glucose values (but not by glycosylated hemoglobin), improved in the supervised- exercise group despite reduced daily insulin dosage. Cardiorespiratory fitness, as measured by voluntary maximum treadmill time (Bruce protocol) and submaximal exercise heart rates, also improved. No changes were observed in the unsupervised control group.

Genetics of Familial Hypercholesterolemia

Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein (LDL) cholesterol and premature cardiovascular disease, with a prevalence of approximately 1 in 200–500 for heterozygotes in North America and Europe. Monogenic FH is largely attributed to mutations in the LDLR, APOB, and PCSK9 genes. Differential diagnosis is critical to distinguish FH from conditions with phenotypically similar presentations to ensure appropriate therapeutic management and genetic counseling. Accurate diagnosis requires careful phenotyping based on clinical and biochemical presentation, validated by genetic testing. Recent investigations to discover additional genetic loci associated with extreme hypercholesterolemia using known FH families and population studies have met with limited success. Here, we provide a brief overview of the genetic determinants, differential diagnosis, genetic testing, and counseling of FH genetics.

Familial chylomicronemia syndrome and response to medium-chain triglyceride therapy in an infant with novel mutations in GPIHBP1

BACKGROUND Severe hypertriglyceridemia predisposes to attacks of acute pancreatitis, a serious condition complicated by multiorgan failure, pancreatic necrosis, and mortality rates up to 20% in adults and 6.5% in children. OVERVIEW We describe an infant who suffered from an episode of acute pancreatitis from severe hypertriglyceridemia. Two major challenges complicate the case: identifying the etiology of severe hypertriglyceridemia and finding an efficacious treatment. A thorough history, physical examination, and laboratory workup failed to identify a clear etiology, prompting a genetic workup that identified compound heterozygous mutations in the glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) gene. This patients hypertriglyceridemia responded to an infant formula rich in medium chain triglycerides (MCTs), and she remained free of pancreatitis 6 months later. CONCLUSIONS This case highlights the need to pursue a genetic evaluation in the absence of secondary causes of severe hypertriglyceridemia in infants. Patients with mutations in GPIHBP1 fail to respond to currently available lipid-lowering agents so dietary management-specifically, an extremely low-fat diet and supplementation with MCT-remains the cornerstone of therapy. Treatment in infants should focus on dietary measures rather than pharmacologic agents.