Lamberto Manzoli

Analysis of potential predictors of depression among coronary heart disease risk factors including heart rate variability, markers of inflammation, and endothelial function.

AIMS We investigated the relationship between autonomic nervous system balance, systemic immune activation, endothelial dysfunction, and depression in patients free of coronary heart disease (CHD) with increased CHD risk. METHODS AND RESULTS Depression status (Beck Depression Inventory, BDI), selected CHD risk factors, inflammation markers, measures of heart rate variability (HRV), and indices of endothelial function (flow-mediated dilation, FMD) were evaluated in 415 subjects free of CHD, diabetes mellitus, and other life-threatening conditions, with at least two CHD risk factors among the following: older age, male gender, current smoking, hypertension, and dislipidaemia. Overall, 51.7% of the participants were males, aged 57.6 +/- 8.8 years on average (minimum 30, maximum 70). Almost half were hypertensive, 43.9% were dyslipidemic, 30.4% current smokers, and 23.1% showed a depressive symptomatology (BDI > or = 10). Logistic regression showed that, as compared with non-depressed individuals and after adjustment for age, gender, and hypertension, depressive subjects were significantly more likely to be smokers, to have higher total cholesterol, higher C-reactive protein, and Interleukin-6. In addition, depressed subjects were more likely to have altered HRV and their FMD was severely impaired (adjusted odds ratio of 1% increase = 0.72; 95% CI: 0.61-0.86). CONCLUSION Our data indicate an independent association between depression and impaired HRV, systemic inflammatory, and endothelial function. These mechanisms play a role not only in the complication of advanced forms of disease, but also promote and/or accelerate the early disease and connect depression and CHD.

Meta-Analysis of the Brain-Derived Neurotrophic Factor Gene (BDNF) Val66Met Polymorphism in Anxiety Disorders and Anxiety-Related Personality Traits

Objective: Brain-derived neurotrophic factor (BDNF) is potentially involved in the pathogenesis of anxiety. We carried out meta-analyses to evaluate the relationship between the BDNF Val66Met (valine, methionine) polymorphism and anxiety disorders (AD) or anxiety-related personality traits (ARPT). Methods: Medline, Embase and PsycINFO were searched up to December 2007. We investigated 3 outcomes related to BDNF Val66Met polymorphisms: (1) clinically diagnosed cases of AD; (2) ARPT in subjects without psychiatric diagnoses, assessed either by the Neuroticism scale of NEO-Personality Inventory forms (NEO-PI, NEO-PI-R, NEO-FFI), or by (3) the Harm Avoidance (HA) scale of Tridimensional Personality Questionnaire (TPQ) or its extended version Temperament and Character Inventory (TCI). Results: Seven case-control studies were selected for AD, including 1,092 cases and 8,394 controls, while 5 cross-sectional studies for Neuroticism (n = 1,633) and 4 for HA (n = 607). Both Met/Met and Val/Met individuals, as compared to Val/Val, showed a statistically significant lower Neuroticism score [SMD = –0.24 (95% CI: –0.44, –0.04), and –0.11 (95% CI: –0.22, –0.01), respectively]. No significant association was found between BDNF Val66Met polymorphism and AD [OR = 1.13 (95% CI: 0.85–1.52) for Met/Met versus Val/Val] or HA [SMD = 0.11 (95% CI: –0.19, 0.42) for Met/Met vs. Val/Val]. Conclusions: The low number of studies on this topic and their limited sample size, along with the inner limits in the definition of anxiety phenotypes, suggest caution in the interpretation of these results. Larger additional studies possibly investigating the interaction with other genes and environmental exposures are required to confirm these results.

Meta-Analysis of Selective Serotonin Reuptake Inhibitors in Patients With Depression and Coronary Heart Disease

The occurrence of depression in patients with coronary heart disease (CHD) substantially increases the likelihood of a poorer cardiovascular prognosis. Although antidepressants are generally effective in decreasing depression, their use in patients with CHD is controversial. We carried out a meta-analysis to evaluate the health effects of selective serotonin reuptake inhibitors (SSRIs) versus placebo or no antidepressants in patients with CHD and depression. Observational studies and randomized controlled trials (RCTs) were searched in MEDLINE, EMBASE, PsycINFO, Cochrane Controlled Clinical Trial Register and other trial registries, and references of relevant articles. Primary outcomes were readmission for CHD (including myocardial infarction, unstable angina, and stroke) and all-cause mortality; the secondary outcome was severity of depression symptoms. Seven articles on 6 RCTs involving 2,461 participants were included. One study incorrectly randomized participants, and another was a reanalysis of RCT data. These were considered observational and analyzed separately. When only properly randomized trials were considered (n = 734 patients), patients on SSRIs showed no significant differences in mortality (risk ratio 0.39, 95% confidence interval 0.08 to 2.01) or CHD readmission rates (0.74, 0.44 to 1.23) compared to controls. Conversely, when all studies were included, SSRI use was associated with a significant decrease in CHD readmission (0.63, 0.46 to 0.86) and mortality rates (0.56, 0.35 to 0.88). A significantly greater improvement in depression symptoms was always apparent in patients on SSRIs with all selected indicators. In conclusion, in patients with CHD and depression, SSRI medication decreases depression symptoms and may improve CHD prognosis.

The efficacy of influenza vaccine for healthy children: a meta-analysis evaluating potential sources of variation in efficacy estimates including study quality.

Background: Two systematic reviews evaluating influenza vaccine efficacy in healthy children have recently been published. Although quantitative summary estimates were similar, authors’ conclusions were quite contrasting. We carried out another meta-analysis reevaluating study inclusion criteria and using metaregression techniques in addition to sensitivity and subgroups analyses to evaluate potential sources of heterogeneity of efficacy estimates, including methodologic quality of studies. Methods: Only randomized clinical studies assessing the efficacy of influenza vaccine in healthy children/adolescents (age ≤18 years) for preventing naturally occurring influenza and/or acute otitis media cases were included. Summary estimates of effect were obtained using a random effects model. The methodologic quality of each study was assessed using 3 systems: Chalmers scale, Jadad scale and Schulz components (randomization, allocation concealment and double-blinding). Results: The overall vaccination efficacy was 36% (95% confidence interval: 31–40%) against clinically diagnosed illnesses (evaluated by 19 randomized clinical studies for a total of 247,517 children); 67% (51–78%) against laboratory-confirmed cases (18 trials, n = 8574); and 51% (21–70%) against acute otitis media (11 trials, n = 11,349). Significant sources of between-study heterogeneity were participants’ age and study quality both directly correlated with the efficacy. When the analysis was performed excluding USSR studies, the overall efficacy of the vaccine in preventing clinical cases substantially increased (from 36% to 61%). Conclusions: These findings may indicate that the vaccine efficacy might be greater than the overall estimates. Although no safety and cost considerations are addressed in this analysis, the present findings support vaccination as a possible option for the prevention of influenza in healthy children and adolescents.

Effects of selective serotonin reuptake inhibitor therapy on endothelial function and inflammatory markers in patients with coronary heart disease.

We investigated the effect of sertraline on inflammation and endothelial function in patients with coronary heart disease (CHD) and symptoms of depression. One hundred patients with CHD and depression were randomized in a double‐blind fashion to receive sertraline or a placebo. We measured symptoms of depression (Beck Depression Inventory (BDI) score), levels of inflammatory markers (C‐reactive protein (CRP) and interleukin‐6 (IL‐6)), and flow‐dependent endothelium‐mediated dilation (FMD) before and after 20 weeks of treatment. Sertraline treatment significantly reduced the BDI score as compared with both baseline and placebo. Levels of CRP and IL‐6 also decreased after 20 weeks of sertraline treatment, whereas they did not significantly change in the placebo group. There was a significant improvement in FMD in patients on sertraline treatment, whereas there was no change in FMD in the placebo group. Sertraline improves endothelial function and reduces inflammatory markers in patients with CHD and symptoms of depression.

Polycystic Ovary Syndrome Is a Risk Factor for Type 2 Diabetes: Results From a Long-Term Prospective Study

Polycystic ovary syndrome (PCOS) recently has been identified as a risk factor associated with type 2 diabetes. However, the evidence derives from cross-sectional observational studies, retrospective studies, or short-term prospective studies. This long-term prospective study of a large cohort of women with PCOS, followed from youth to middle age, aimed at estimating, for the first time, the incidence and potential predictors of type 2 diabetes in this population. A total of 255 women with PCOS were followed for at least 10 years (mean follow-up 16.9 years). Six women were patients with diabetes at baseline, and another 42 women developed type 2 diabetes during the follow-up. The incidence rate of type 2 diabetes in the study population was 1.05 per 100 person-years. The age-standardized prevalence of diabetes at the end of follow-up was 39.3%, which is significantly higher with respect to that of the general Italian female population of a similar age (5.8%). The likelihood of developing type 2 diabetes significantly increased as BMI, fasting glucose, and glucose area under the curve at baseline increased and significantly decreased as sex hormone–binding globulin (SHBG) levels at follow-up increased. This study demonstrates that the risk of type 2 diabetes is markedly elevated in middle-aged women with PCOS and suggests including BMI, glucose, and SHBG-circulating levels in the risk stratification.

Prenatal identification of invasive placentation using magnetic resonance imaging: systematic review and meta‐analysis

To assess systematically the performance of prenatal magnetic resonance imaging (MRI) in diagnosing the presence, degree and topography of disorders of invasive placentation and to explore the role of the different MRI signs in predicting these disorders. The diagnostic accuracy of ultrasound and MRI in the detection of invasive placentation was also compared.

Meta-analysis of the immunogenicity and tolerability of pandemic influenza A 2009 (H1N1) vaccines

Background Although the 2009 (H1N1) influenza pandemic officially ended in August 2010, the virus will probably circulate in future years. Several types of H1N1 vaccines have been tested including various dosages and adjuvants, and meta-analysis is needed to identify the best formulation. Methods We searched MEDLINE, EMBASE, and nine clinical trial registries to April 2011, in any language for randomized clinical trials (RCTs) on healthy children, adolescents, adults and the elderly. Primary outcome was the seroconversion rate according to hemagglutinination-inhibition (HI); secondary outcomes were adverse events. For the primary outcome, we used head-to-head meta-analysis and multiple-treatments meta-analysis. Results Eighteen RCTs could be included in all primary analyses, for a total of 76 arms (16,725 subjects). After 2 doses, all 2009 H1N1 split/subunit inactivated vaccines were highly immunogenic and overcome CPMP seroconversion criteria. After 1 dose only, all split/subunit vaccines induced a satisfactory immunogenicity (> = 70%) in adults and adolescents, while only some formulations showed acceptable results for children and elderly (non-adjuvanted at high-doses and oil-in-water adjuvanted vaccines). Vaccines with oil-in-water adjuvants were more immunogenic than both nonadjuvanted and aluminum-adjuvanted vaccines at equal doses and their immunogenicity at doses < = 6 µg (even with as little as 1.875 µg of hemagglutinin antigen) was not significantly lower than that achieved after higher doses. Finally, the rate of serious vaccine-related adverse events was low for all 2009 H1N1 vaccines (3 cases, resolved in 10 days, out of 22826 vaccinated subjects). However, mild to moderate adverse reactions were more (and very) frequent for oil-in-water adjuvanted vaccines. Conclusions Several one-dose formulations might be valid for future vaccines, but 2 doses may be needed for children, especially if a low-dose non-adjuvanted vaccine is used. Given that 15 RCTs were sponsored by vaccine manufacturers, future trials sponsored by non-industry agencies and comparing vaccines using different types of adjuvants are needed.

Oral contraceptives and venous thromboembolism: a systematic review and meta-analysis.

AbstractBackground: An association between oral contraceptive (OC) use and venous thromboembolism (VTE) has long been recognized. However, no summary estimates of the increase in VTE risk associated with OC use have been available since 1995, and no meta-analyses have evaluated the VTE risk of new preparations containing drospirenone. Objective: The aim of the study was to carry out a meta-analysis to summarize existing evidence on the association between venous VTE and OC use, and to investigate how such an association may vary according to the type of OC, OC user characteristics, study characteristics and biases. Methods: Relevant cohort or case-control studies were searched in MEDLINE and other electronic databases up to May 2010, with no language restriction. Data were combined using a generic inverse-variance approach. Meta-regression in addition to stratification was used to explore potential predictors of the summary estimate of risk. Results: Sixteen cohort and 39 case-control studies were included in at least one comparison. Overall, the odds ratio (OR) of OC users versus non-users was 3.41 (95% CI 2.98, 3.92). This estimate was based upon nine cohort studies evaluating approximately 12 000 000 person-years, and 23 case-control studies including approximately 45 000 women. VTE risk for OC users was significantly lower in studies evaluating ‘all VTE cases’ than in those evaluating ‘idiopathic VTE only’ (OR 3.09 and 4.94, respectively). Among the carriers of genetic mutations G20210A and Factor V Leiden (FVL), OC users showed a significantly increased VTE risk compared with non-users (OR 1.63; 95% CI 1.01, 2.65, and OR 1.80; 95% CI 1.20, 2.71, respectively). When the newest OCs containing drospirenone were compared with non-drospirenone-containing OCs (except those containing levonorgestrel only), VTE risk did not significantly increase (OR 1.13; 95% CI 0.94, 1.35). Conclusions: This meta-analysis confirms that OC use significantly increases VTE risk. The strength of this association, however, varies according to the generation of OC, type of outcome and presence of a genetic mutation, with ORs ranging from 3 to 5.

Effectiveness and harms of seasonal and pandemic influenza vaccines in children, adults and elderly: A critical review and re-analysis of 15 meta-analyses

Fifteen meta-analyses have been published between 1995 and 2011 to evaluate the efficacy/effectiveness and harms of diverse influenza vaccines—seasonal, H5N1 and 2009(H1N1) —in various age-classes (healthy children, adults or elderly). These meta-analyses have often adopted different analyses and study selection criteria. Because it is difficult to have a clear picture of vaccine benefits and harms examining single systematic reviews, we compiled the main findings and evaluated which could be the most reasonable explanations for some differences in findings (or their interpretation) across previously published meta-analyses. For each age group, we performed analyses that included all trials that had been included in at least one relevant meta-analysis, also exploring whether effect sizes changed over time. Although we identified several discrepancies among the meta-analyses on seasonal vaccines for children and elderly, overall most seasonal influenza vaccines showed statistically significant efficacy/effectiveness, which was acceptable or high for laboratory-confirmed cases and of modest magnitude for clinically-confirmed cases. The available evidence on parenteral inactivated vaccines for children aged < 2 y remains scarce. Pre-pandemic “avian” H5N1 and pandemic 2009 (H1N1) vaccines can achieve satisfactory immunogenicity, but no meta-analysis has addressed H1N1 vaccination impact on clinical outcomes. Data on harms are overall reassuring, but their value is diminished by inconsistent reporting.