Resting Heart Rate Variability, Inflammation, and Insulin Resistance in Overweight and Obese Adolescents.

BACKGROUND: The prevalence of obesity is increasing in young people in the United States. Lately, low-grade inflammation is recognized as accompanying obesity, a known risk factor for type 2 diabetes. Autonomic dysfunction is a prominent feature of adult diabetes, but its prevalence in adolescents in prediabetic states or with diabetes risk factors is unknown. We undertook to study obesity, inflammation, insulin resistance, and autonomic dysfunction together in a population of adolescents aged 13-18 years. METHODS: Subjects gave a blood sample for cytokine analysis and a 5-min resting EKG for analysis of resting heart rate variability. TNF-α, IL-6, c-reactive protein (CRP), MCP-1, and IL-10 were analyzed by enzyme-linked immunosorbent assay, and Fourier Transform was applied to electrocardiographic recordings of R-R intervals for analysis in frequency space. The HOMA calculation was used as an index of insulin sensitivity. RESULTS: TNF-α, IL-6, CRP, MCP-1, HOMA, and insulin levels, but not serum glucose or IL-10, were higher in the obese subjects. Low-frequency (0.04-0.15 Hz) and high-frequency (0.15-0.4 Hz) fluctuations of R-R intervals were lower in the obese subjects, but the normalized low-frequency power was not different, suggesting proportional reduction in variability in both ranges and impairment of both sympathetic and parasympathetic systems. CONCLUSIONS: Chronic low-grade inflammation, insulin resistance, and autonomic dysfunction are present at an early age in obese youths; early detection of inflammation may facilitate meaningful lifestyle changes in this high-risk group.

Epidemiology and comorbidities of polycystic ovary syndrome in an indigent population.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. The aims of this study were to provide an estimate of the prevalence of PCOS in clinical practice; compare the risk of established cardiovascular risk factors, cardiovascular disease, and other comorbid conditions in women with PCOS to that of age- and race-matched controls; and explore the total costs of care that can be attributed to PCOS. METHODS: Louisiana Medicaid claims data were used to identify women with PCOS or its defining features and a control group in a ratio of 1:3. The prevalence of PCOS, cardiovascular risk factors (diabetes, dyslipidemia, dysmetabolic syndrome, glucose intolerance, hypertension, and obesity), key comorbidities (anxiety, bipolar disorders, depression, eating disorders, infertility, obstructive sleep apnea), and diagnosed cardiovascular disease were measured. RESULTS: During 2010, the prevalence of PCOS was 0.88%. Women with PCOS were more likely to have a diagnosis of diabetes (odds ratio [OR], 4.35; 95% confidence interval [CI], 3.63-5.21), dyslipidemia (OR, 3.56; 95% CI, 3.04-4.19), dysmetabolic syndrome (OR, 23.46; 95% CI, 13.64-40.36), glucose intolerance (OR, 5.46; 95% CI, 3.10-9.60), hypertension (OR, 2.76; 95% CI, 2.41-3.18), obesity (OR, 5.79; 95% CI, 5.07-6.62), infertility (OR, 23.42; 95% CI, 10.63-51.61), obstructive sleep apnea (OR, 6.47; 95% CI, 3.62-11.55), anxiety (OR, 1.76; 95% CI, 1.53-2.04), bipolar disorders (OR, 1.94; 95% CI, 1.55-2.44), and depression (OR, 2.22; 95% CI, 1.94-2.54) than did controls. Average total costs of care for the year was $5551 in the PCOS group and $3496 in the control group. After controlling for the effects of other variables, the average total cost of care for PCOS was $637 higher than that of the control group. Other variables that contributed significantly to the total costs of care included race, age, acute myocardial infarction, transient ischemic attack, peripheral artery disease, anxiety, depression, bipolar disorders, hypertension, diabetes, and dyslipidemia. CONCLUSIONS: Although the clinical burden of PCOS is high, it is diagnosed less frequently in clinical practice compared with systematic screening studies. This is concerning considering that PCOS is associated with cardiovascular risk factors and other comorbidities. Mean total costs of care for the PCOS group was higher than the mean total costs of care for the control group. Polycystic ovary syndrome is independently associated with an increase in mean total costs of care.

Screening for the metabolic syndrome in a public care hospital clinic population: a simple measurement of waist circumference.

BACKGROUND: Metabolic syndrome is a collection of anthropomorphic and metabolic derangements that, taken together, constitute a strong predictor of stroke, cardiovascular disease, type 2 diabetes, and perhaps other disorders. Diagnosing the metabolic syndrome according to presently accepted definitions requires a mixture of anthropomorphic and laboratory measurements. In indigent patient populations or locations that lack adequate laboratory facilities, a noninvasive low-cost or cost-free alternative would be beneficial as a preliminary screening measure. METHODS: To identify potential means for the diagnosis, we evaluated anthropomorphic measures individually and in combination for their predictive value against the standard classification. Receiver operator characteristic curves identified optimal cutoff values for the variables tested, and consideration of sensitivity and specificity were considered concerning the consequences of false negatives and positives. RESULTS: Receiver operator characteristic curves showed that only waist circumference in men gave acceptable specificity and sensitivity. Combinations of measurements did not improve on a simple measurement of waist circumference. CONCLUSIONS: Waist circumference was a potentially useful single indicator in men but not in women. Other values and combinations were evaluated as well. Waist measurement alone may serve as sufficient screening in men in locations where laboratory facilities are lacking or funds are severely limited, as in developing countries.

Stability of ziprasidone mesylate in an extemporaneously compounded oral solution.

OBJECTIVES: To formulate a liquid preparation of ziprasidone in a convenient concentration to allow dosing of less than 20 mg and of sufficient chemical and physical stability to enable an entire prescription or course of treatment to be prepared in a single batch. METHODS: Geodon for injection (ziprasidone mesylate), 20 mg/mL, was diluted to 2.5 mg/mL in a commercially available sugar-free and alcohol-free, flavored syrup and stored at room temperature under ambient fluorescent light illumination, at room temperature in darkness, and under refrigeration. The ziprasidone content was measured in samples at various time intervals using a stability-indicating high-performance liquid chromatographic method. RESULTS: When refrigerated, the ziprasidone syrup that was compounded in a commercially available, sugar-free and alcohol-free vehicle maintained at least 90% of stated potency for at least 6 weeks. Samples stored under other conditions were less stable, underscoring the manufacturer's labeling regarding refrigerated storage of the reconstituted injection. CONCLUSIONS: The findings suggest that chemical and physical stability are maintained for 2 weeks under refrigeration, allowing the convenience of compounding for the long-term needs of a particular patient, rather than daily compounding. The only storage condition we recommend is refrigeration at 5°C.

Rapid, simple assay for ziprasidone mesylate in extemporaneously compounded oral solutions.

A high-performance liquid chromatographic assay method was developed to facilitate stability studies of extemporaneously compounded oral liquid formulations of ziprasidone. The method is simple and precise within the needs of the pharmaeutical profession. The throughput time is approximately 7 minutes per sample. The method is easily adaptable for inidividual needs.

Inflammation in chronic heart failure.

OBJECTIVE: To summarize findings regarding the association of inflammatory processes with chronic heart failure (HF). DATA SOURCES: We conducted PubMed/MEDLINE searches (1966-January 2008) of primary literature using the following key words: ACE inhibitors, allopurinol, angiotensin-receptor antagonists, cardiomyopathy, chemokines, cytokines, diuretics, heart failure, inflammation, interleukins, HMG-CoA reductase inhibitors, immunotherapy, medications used in heart failure, thalidomide, tumor necrosis factor, and uric acid. STUDY SELECTION AND DATA EXTRACTION: All articles that appeared to be relevant were read; of 305 articles examined, 87 were selected for discussion. Articles were selected if they were written in English and focused on any of the key words or appeared to have substantial content addressing inflammation in HF. DATA SYNTHESIS: Cytokines, uric acid, and other inflammatory mediators are associated with physiologic effects that are also prominent features of HF (eg, reduced contractility and cardiac output, endothelial dysfunction, hypercoagulability, autonomic dysfunction as evidenced by reduced resting heart rate variability, insulin resistance). With the exception of elevated tumor necrosis factor-alpha as a cause of insulin resistance, it is not clear whether elevated inflammatory mediators directly cause HF signs and symptoms or whether they are incidental markers. Awareness of these associations has occurred relatively recently; there have been few clinical studies of efforts to directly modify inflammatory mediators. Most currently accepted drug therapies of HF reduce concentrations of circulating cytokines, but the significance of these findings awaits directed study. CONCLUSIONS: Loss of myocardial function, autonomic dysfunction, and glucose intolerance are interrelated and linked by underlying chronic low-grade inflammation. Drug therapy with statins, pentoxifylline, and perhaps urate-lowering agents, in addition to current therapies, holds promise for treatment of HF.

Venous thromboembolism prevention in acutely ill nonsurgical patients.

OBJECTIVE: To review recent advances in the prevention of venous thromboembolism (VTE) in acutely ill nonsurgical inpatients. DATA SOURCES: A MEDLINE search (1966-March 2005) was done to identify relevant articles relating to prevention of VTE in acutely ill nonsurgical inpatients. STUDY SELECTION AND DATA EXTRACTION: Four major prophylaxis trials, one registry, one guideline, and supporting articles representative of the subject matter from the last few years were included. DATA SYNTHESIS: Enoxaparin, dalteparin, fondaparinux, and unfractionated heparin 5000 units every 8 hours are effective in reducing the risk of VTE in acutely ill medical patients, but such prophylaxis is currently underused. Barriers to be overcome include recognition of the importance of VTE in this population, definition of the optimal strategy to assess risks, optimal timing of the risk assessment, optimal prophylactic regimen for a given level of risk or disease state, and optimal duration of prophylaxis. We recommend that acutely ill medical inpatients should be risk-stratified early in their hospitalization. At this time, the specific risk-assessment protocol should be derived from the trial(s) of the available formulary agent(s). Decisions about providing prophylaxis must also be made considering anticoagulant contraindications and renal function. Mechanical methods of prophylaxis should be considered as monotherapy only if an anticoagulant contraindication exists. The optimal duration of prophylaxis is not known, but 14 days was used in recent studies. CONCLUSIONS: Prophylaxis of VTE in acutely ill medical inpatients is underused. Data provide some guidance for increasing awareness and optimizing patient care.