Early Cognitive Change in the General Population: How Do Different Definitions Work?

OBJECTIVES: To explore the application of existing classifications of mild cognitive impairment (MCI) and associated states in a large population sample. DESIGN: Prospective cohort study, baseline phase (cross-sectional analysis). SETTING: Large-scale multicenter study in the United Kingdom. PARTICIPANTS: Thirteen thousand four individuals aged 65 and older from the Medical Research Council Cognitive Function and Aging Study. From this, a subsample of 2,640 individuals was selected and completed a more-detailed cognitive assessment. MEASUREMENTS: Information on sociodemographic status, general health, cognitive impairment (measured using the Mini-Mental State Examination), and functional ability was collected in a structured interview at baseline. The Geriatric Mental State Automated Geriatric Examination for Computer-Assisted Taxonomy and the Cambridge Cognitive Examination were used in assessment to determine cognitive status. Using a systematic literature review to collect all symptom classifications for nonnormal dementia states, these were then operationalized retrospectively. Each participant was classified according to each. RESULTS: Population prevalence estimates were variable (range 0.1-42%), reflecting differences in the focus and content of each state. Limited overlap existed between states such that many individuals were concurrently classified as normal and impaired. This highlights the heterogeneity in classification as captured using different definitions. CONCLUSION: Classification of cognitively impaired and cognitively normal individuals is dependent on the way criteria are defined and operationalized. Each classification captures a unique group of individuals, with little concordance. Given the importance of early detection of dementia and the calls for screening, and recruitment into pharmacological trials of cognitively impaired individuals, there is an urgent need for an agreed-upon standard MCI case definition to use as a criterion standard.     

Sudden Cardiac Death in the General Population: Can We Improve Risk Stratification and Prevention?

A total of 15 to 20% of deaths worldwide are sudden (within 1 hour of symptom onset). Our ability to predict and prevent sudden cardiac death (SCD) in the general population, in which 85% have no known organic heart disease (OHD) or stable OHD with left ventricular ejection fraction >40%, is limited to poor. The purpose of this commentary is to suggest a new approach to SCD in this population. Oxidative stress is a common thread in development and progression of the major cardiac diseases associated with SCD. It has a profound adverse effect upon heart rate variability (HRV), sympathetic tone (S), and parasympathetic tone (P). Recently, developed technology finally has allowed accurate measures of S and P. Using this technique, the general population can be screened, those at risk for SCD can be identified with a higher degree of success, and preventative measures instituted. For example, in 133 geriatric type 2 diabetics with S and/or P abnormalities upon screening, the potent and natural antioxidant (r)α lipoic acid reduced SCD (relative risk reduction) 43% ( p  = 0.0076), mean follow-up 6.31 years. Diabetes mellitus patients have high glycemic oxidative stress. Addressing oxidative stress S and P abnormalities can reduce SCD. S and P screening of the general population will be discussed.     

Juvenile Fibromyalgia: Different from the Adult Chronic Pain Syndrome?

While a majority of research has focused on adult fibromyalgia (FM), recent evidence has provided insights into the presence and impact of FM in children and adolescents. Commonly referred as juvenile fibromyalgia (JFM), youths, particularly adolescent girls, present with persistent widespread pain and cardinal symptoms observed in adult FM. A majority of youth with JFM continue to experience symptoms into adulthood, which highlights the importance of early recognition and intervention. Some differences are observed between adult and juvenile-onset FM syndrome with regard to comorbidities (e.g., joint hypermobility is common in JFM). Psychological comorbidities are common but less severe in JFM. Compared to adult FM, approved pharmacological treatments for JFM are lacking, but non-pharmacologic approaches (e.g., cognitive-behavioral therapy and exercise) show promise. A number of conceptual issues still remain including (1) directly comparing similarities and differences in symptoms and (2) identifying shared and unique mechanisms underlying FM in adults and youths.     

Antiphospholipid Syndrome in Systemic Lupus Erythematosus: Is the Whole Greater Than the Sum of Its Parts?

This article compares the manifestations of systemic lupus erythematosus (SLE) in the presence and absence of antiphospholipid antibodies (aPLs), the hallmark autoantibodies of antiphospholipid syndrome (APS). The combination of SLE and APS appears to be of greater concern than either entity alone. APS complicates SLE by adding a vaso-occlusive factor to the inflammatory component that adversely affects the prognosis of those who have lupus and aPLs. The increase in both morbidity and mortality when both are present has significant therapeutic implications. Anticoagulation may be a safer and more appropriate therapeutic option than instituting a regimen of corticosteroids and immunosuppressive agents with all their attendant adverse effects. It falls upon the physician to clearly define the disease entity and fully evaluate the disease process.     

Role of Ribomunyl® in the Prevention of Recurrent Respiratory Tract Infections in Adults

Recurrent respiratory tract infections (RRTIs) in adults are the result of an imbalance between lung defense mechanisms, and bacterial burden. Antibacterial treatments can temporarily restore the equilibrium between host and bacterial load, but do not prevent recurrence of infection. An alternative approach to prevent recurrence of infection is treatment with an immunostimulant, which provides immune protection against repeated bacterial and viral infection. All immunostimulant products are bacterial in origin: lysates (first generation immunostimulants), or bacterial extracts, like bacterial ribosomes, or membrane proteoglycans. This review highlights the current state of knowledge regarding the use of immunostimulants in adults with RRTIs, taking the ribosomal immunostimulant Ribomunyl((R)) as an example. Many studies are available on the mechanism of action and clinical efficacy in prevention of RRTIs in adults treated with Ribomunyl((R)). The effect of this immunostimulant on anti-infectious responses is explained by a stimulation of both nonspecific (innate) and specific (adaptive) immunity. In order to obtain a global overview of the therapeutic efficacy of Ribomunyl((R)) the most pertinent trials were selected from the literature based on adequate patient numbers and good methodology. Results of double-blind placebo-controlled trials using Ribomunyl((R)) for the treatment of different upper or lower RRTIs have demonstrated a statistically significant reduction in the number of infectious episodes and as a consequence, a decrease in antibacterial consumption, after 3 and 6 months of treatment. The tolerance profile of Ribomunyl((R)) was good in all studies. Economic evaluations suggest that savings can be made in healthcare expenditure, in patients with recurrent episodes of infection. It is concluded that Ribomunyl((R)) is effective in preventing and reducing upper and lower respiratory tract infections in adults. The product may also have an impact on reducing the development of bacterial resistance, as a result of fewer courses of antibacterials required to treat patients with RRTIs.     

Acute Coronary Syndrome in the Patient with Diabetes: Is the Management Different?

Diabetic patients who present with an acute coronary syndrome (ACS) have a particularly adverse prognosis, largely contributed by increased platelet reactivity and higher burden of disease severity. Diabetic patients with ACS derive a greater benefit from established therapies, particularly platelet-inhibiting therapies, including clopidogrel pretreatment, and glycoprotein IIb/IIIa inhibitor use. Recent data show intense ADP-P2Y12 platelet receptor inhibition with prasugrel is of particular clinical value in the diabetic patient with ACS, without excessive bleeding. Diabetic patients with ACS also benefit more from aggressive revascularization strategies. Recent data show the benefit of drug-eluting stents in the setting of primary percutaneous coronary intervention for ST-segment elevation myocardial infarction in decreasing target vessel revascularization up to 2 years, particularly in patients at highest risk for restenosis with bare metal stents (likely diabetic patients). This review summarizes the data supporting the key pharmacologic and revascularization management strategies to guide the clinician in taking care of diabetic patients who present with an ACS event.     

REPLY to “Association Between Plasmatic Oxidative Stress and Thrombosis in Primary Antiphospholipid Syndrome”

Journal of Thrombosis and Thrombolysis -     

Primary Thrombosis Prophylaxis in Persistently Antiphospholipid Antibody-Positive Individuals: Where Do We Stand in 2018?

Purpose of review

To update our previous literature review and management recommendations on risk stratification and primary thrombosis prophylaxis in persistently antiphospholipid antibody (aPL)-positive individuals.

Recent Findings

The estimated annual thrombosis incident rate (ATIR) among aPL-positive individuals with or without systemic autoimmune disease (SAIDx) is 0 to 5.3%, probably very low (<?1%/year) in those with no other SAIDx and thrombosis risk factors. Risk stratification based on aPL profile, age, additional SAIDx, and traditional cardiovascular disease (CVD) or venous thrombosis risk factors is crucial to determine the risk of first thrombosis in aPL-positive patients. The protective effect of low-dose aspirin for primary thrombosis prophylaxis prevention is not supported by randomized controlled data. Hydroxychloroquine is protective against thrombosis in aPL-positive SLE patients; however, its role in aPL-positive individuals with other SAIDx remains uncertain. Statins downregulate proinflammatory and prothrombotic biomarkers among antiphospholipid syndrome (APS) patients and may have a role in aPL-positive individuals with high CVD risk.

Summary

The optimal primary thrombosis prevention strategy in patients with clinically significant aPL profiles should include (a) regular screening and elimination of non-aPL thrombosis risk factors, (b) optimal management of concomitant SAIDx, (c) patient counseling and education, and (d) use of CVD risk prediction tools and guidelines to perform risk-benefit calculations regarding low-dose aspirin, hydroxychloroquine, and/or statin therapy.

     

Primary Thrombosis Prophylaxis in Antiphospholipid Antibody–Positive Patients: Where Do We Stand?

Persistently positive antiphospholipid antibodies (aPLs) with thrombosis and/or pregnancy morbidity are the hallmark of the antiphospholipid syndrome. However, aPL-positive patients with no prior history of thrombosis exist. On the basis of a limited number of studies that predominantly included systemic lupus erythematosus patients, aPL-positive patients without previous thrombosis have a 0% to 3.8% annual incident thrombosis risk. Given that every positive aPL test is not clinically significant and every aPL-positive patient does not have the same thrombosis risk, risk stratification (based on aPL profile, age, systemic autoimmune diseases, and traditional cardiovascular disease or venous thrombosis risk factors) is crucial to determine the first thrombosis risk in aPL-positive patients. The optimal primary thrombosis prevention strategy in patients with clinically significant aPL profiles should include 1) regular monitoring and elimination of non-aPL thrombosis risk factors, 2) aggressive management of clinical and subclinical systemic autoimmune disease activity, and 3) patient counseling and education. The protective effect of low-dose aspirin against incident thrombosis in patients with clinically significant aPL profiles is not supported by randomized controlled data; general population cardiovascular disease risk prediction tools and prevention guidelines formulated based on risk–benefit calculations should play a role in the decision whether to recommend low-dose aspirin. The effectiveness of hydroxychloroquine, statins, or their combination remains to be determined by well-designed randomized controlled trials.     

Answer to “REPLY to Association between Plasmatic Oxidative Stress and Thrombosis in Primary Antiphospholipid Syndrome”

Journal of Thrombosis and Thrombolysis - Left atrial appendage (LAA), a blind pouch, accounts for more than 90% of the source of cardiac thrombus formation. Contrast retention (CR) in the LAA has...     

Prognostic Impact of Mild Hypokalemia in Terms of Death and Stroke in the General Population—A Prospective Population Study

Background

Potassium supplementation reduces the risk of cardiovascular mortality and stroke in population studies; however, the prognostic impact of mild hypokalemia in the general population has not been thoroughly investigated. We aimed to investigate associations between mild hypokalemia and endpoints in the general population.

Hyperleptinaemia: the Missing Link in the Metabolic Syndrome?

Leptin’s association with fasting insulin raises the possibility that hyperleptinaemia is an additional component of the Metabolic Syndrome, or perhaps underlies the syndrome. This population-based study of Western Samoans examined the relationship of serum leptin with insulin sensitivity assessed by Homeostatic Model Assessment (HOMA) and components of the Metabolic Syndrome. Two hundred and forty subjects (114 men, 126 women), aged 28–74 years, were drawn from a study conducted in 1991. An oral glucose tolerance test indicated that 59 subjects had diabetes. Diabetic men had higher leptin levels than non-diabetic (6.0 vs 3.2 ng ml⁻¹) but this difference was no longer significant after adjustment for BMI. Leptin levels in diabetic women (24.7 ng ml⁻¹) and non-diabetic women (22.6 ng ml⁻¹) were not different. Leptin was strongly, positively correlated with BMI, fasting insulin and mean blood pressure after adjusting for age and sex (r > 0.43, p < 0.001), irrespective of glucose tolerance status. Linear regression models indicated that leptin was associated with insulin sensitivity independent of age, BMI, waist/hip ratio, triglycerides, HDL-cholesterol, and hypertension. Similar models were computed with mean blood pressure or triglycerides as the dependent variable, and including insulin sensitivity with the independent variables. Leptin was independently associated with mean blood pressure in men, but was not independently associated with triglycerides. Mean levels of 2-h insulin, triglycerides, LDL-cholesterol, and systolic blood pressure varied across tertiles of leptin in men after adjusting for age, BMI, and insulin sensitivity, and mean levels in the top tertile tended to be higher than in the lowest tertile. These results indicate an independent relationship between leptin and insulin sensitivity, but the equivocal results concerning associations of leptin with components of the Metabolic Syndrome make it unlikely that leptin affects these directly. © 1997 by John Wiley & Sons, Ltd.     

Prevention of restenosis: is angioplasty the answer?

"The drug-coated balloon has the potential to improve the limited results of drug-eluting stents"