Is the Prevalence of Metabolic Syndrome and Metabolic Abnormalities Increased in Early Schizophrenia? A Comparative Meta-Analysis of First Episode,Untreated and Treated Patients

We aimed to discover whether metabolic complications of schizophrenia (SZ) are present in first episode (FE) and unmedicated (UM) patients, in comparison with patients established on antipsychotic medication (AP).

Method:

A systematic search, critical appraisal, and meta-analysis were conducted of studies to December 2011 using Medline, PsycINFO, Embase and experts. Twenty-six studies examined FE SZ patients (n = 2548) and 19 included UM SZ patients (n = 1325). For comparison we identified 78 publications involving 24 892 medicated patients who had chronic SZ already established on AP.

Results:

In UM, the overall rate of metabolic syndrome (MetS) was 9.8% using any standardized criteria. Diabetes was found in only 2.1% and hyperglycaemia (>100mg/dl) in 6.4%. In FE, the overall MetS rate was 9.9%, diabetes was found in only 1.2%, and hyperglycaemia in 8.7%. In UM and FE, the rates of overweight were 26.6%, 22%; hypertriglyceridemia 16.9%, 19.6%; low HDL 20.4%, 21.9%; high blood pressure 24.3%, 30.4%; smoking 40.2%, 46.8%, respectively. In both groups all metabolic components and risk factors were significantly less common in early SZ than in those already established on AP. Waist size, blood pressure and smoking were significantly lower in UM compared with FE.

Conclusion:

There is a significantly lower cardiovascular risk in early SZ than in chronic SZ. Both diabetes and pre-diabetes appear uncommon in the early stages, especially in UM. However, smoking does appear to be elevated early after diagnosis. Clinicians should focus on preventing initial cardiometabolic risk because subsequent reduction in this risk is more difficult to achieve, either through behavioral or pharmacologic interventions.Key words: cardiovascular risk, diabetes, lipids, glucose, waist, obesity     

Is ivabradine suitable to control undesirable tachycardia induced by dobutamine in cardiogenic shock treatment?

Inotropic treatment remains the cornerstone for cardiogenic shock, an emergency that requires immediate resuscitative therapy before shock irreversibly damages vital organs. Although the sympathomimetic drug dobutamine is the most widely-used inotropic drug worldwide, it has several side effects including sinus tachycardia. Dobutamine partly restores systolic heart failure (HF); however, it increases the heart rate (HR) which counterbalances the beneficial effects. Ivabradine, a new selective I_f inhibitor, provides specific HR reduction and is indicated in stable coronary artery disease and in stable chronic HF with left ventricular dysfunction. Despite scarce data indicating beneficial effects of ivabradine in sinus tachycardia in various clinical settings, this drug remains contraindicated in acute HF. We propose that ivabradine could help to prevent the dobutamine-induced side effects, and that their combination in clinical practice could lead to pure inotropic effects, useful for the management of cardiogenic shock.     

Cellular and in vivo electrophysiological effects of dronedarone in normal and postmyocardial infarcted rats

We studied the effects of dronedarone (SR 33589) on the action potentials, membrane ionic currents, and arrhythmic activity in control rats and in rats after myocardial infarction, a model known to develop anomalous electrical activity. Dronedarone increased action potential duration in normal hearts. It had little effect on the action potentials that were already prolonged in the postmyocardial infarcted (PMI) rats. Particularly, dronedarone reduced the late sustained K(+) current, I(K) (or Isus) by 69%. Dronedarone induced only a tonic block of I(K). Similar relative inhibitions of I(K) by dronedarone were obtained in young, sham, and PMI rats, even if I(K) was less in sham than in young and further reduced in PMI rats. The EC(50) values were 0.78 and 0.85 microM in sham and PMI rats. Dronedarone induced a weak increase in the fast transient outward current, I(to). Time-to-peak and inactivation time constant of I(to) were decreased by dronedarone that also induced a marked slowing of I(to) recovery from inactivation. Similar effects were observed on the reduced I(to) recorded in PMI rats. Holter monitoring study in control, unthetered animals showed that dronedarone had no proarrhythmic effect. On rats, which after myocardial infarction exhibited ventricular premature beats, dronedarone significantly decreased beat occurrence during the 7-day treatment; this effect was sustained for two more weeks. Thus, dronedarone exerts antiarrhythmic effects on PMI rat heart. Its effects are attributable for the most part to the inhibition of outward K(+) currents and the increase in effective refractory period.     

Physical fitness in people with posttraumatic stress disorder: a systematic review

Purpose: People with posttraumatic stress disorder (PTSD) have an increased risk of cardiovascular diseases (CVD). Physical fitness is a key modifiable risk factor for CVD and associated mortality. We reviewed the evidence-base regarding physical fitness in people with PTSD.

Methods: Two independent reviewers searched PubMed, CINAHL, PsycARTICLES, PEDro, and SPORTDiscus from inception until May 2016 using the key words “fitness” OR “exercise” AND “posttraumatic stress disorder” OR “PTSD”.

Results: In total, 5 studies involving 192 (44 female) individuals with PTSD met the inclusion criteria. Lower baseline physical fitness are associated with greater reductions in avoidance and hyperarousal symptoms, as well as with total, physical, and social symptoms of anxiety sensitivity. Rigorous data comparing physical fitness with age- and gender matched general population controls are currently lacking.

Conclusions: The research field regarding physical fitness in people with PTSD is still in its infancy. Given the established relationships between physical fitness, morbidity and mortality in the general population and the current gaps in the PTSD literature, targets for future research include exploring: (a) whether people with PTSD are at risk of low physical fitness and therefore in need of intensified assessment, treatment and follow-up, (b) the relationships among physical fitness, overall health status, chronic disease risk reduction, disability, and mortality in individuals PTSD, (c) psychometric properties of submaximal physical fitness tests in PTSD, (d) physical fitness changes following physical activity in PTSD, and (e) optimal methods of integrating physical activity programs within current treatment models for PTSD.

• Implications for Rehabilitation

• People with PTSD should aim to achieve 150?minutes of moderate or 75?minutes vigorous physical activity per week while also engaging in resistance training exercises at least twice a week.

• Health care professionals should assist people with PTSD to overcome barriers to physical activity such as physical pain, loss of energy, lack of interest and motivation, generalized fatigue and feelings of hyperarousal.

     

Invalidity for Pseudomonas aeruginosa of an accepted model of bacterial permeability to beta-lactam antibiotics.

The accepted model for the penetration of beta-lactam antibiotics into gram-negative bacteria is that proposed by Zimmermann and Rosselet (Antimicrob. Agents Chemother. 12:368-372, 1977). The model assumes (i) that diffusion of the antibiotic molecules across the outer membrane obeys Fick's law and can be characterized by a permeability constant for any given combination of organism and drug, (ii) that drug hydrolysis within the periplasm obeys Michaelis-Menten kinetics, and (iii) that a steady state is rapidly attained between drug uptake and hydrolysis. The model has allowed accurate prediction of antibiotic MICs for Escherichia coli strains from a knowledge of their beta-lactamase production and permeability characteristics. It has been suggested that the model is inappropriate for Pseudomonas aeruginosa, but attempts to confirm this have been bedevilled by experimental difficulties in estimating permeability coefficients for this species. In the present study, we tested a prediction of the model that the overall resistance of P. aeruginosa transconjugants containing a plasmid-encoded beta-lactamase should continue to depend partly on permeability. Transconjugants with PSE-4 beta-lactamase were constructed in host strains with widely different levels of intrinsic, presumably impermeability-determined resistance. Contrary to the prediction of the model, all the transconjugants developed identical overall levels of resistance to substrate beta-lactams, such as azlocillin and cefoperazone, irrespective of the initial levels of intrinsic resistance of the recipient strains. We conclude that the model is inappropriate for P. aeruginosa, and possible explanations for the organism's behavior are discussed.