Maria Elena Flacco

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.

Electronic Cigarettes Efficacy and Safety at 12 Months: Cohort Study

Objective To evaluate the safety and efficacy as a tool of smoking cessation of electronic cigarettes (e-cigarettes), directly comparing users of e-cigarettes only, smokers of tobacco cigarettes only, and smokers of both. Design Prospective cohort study. Final results are expected in 2019, but given the urgency of data to support policies on electronic smoking, we report the results of the 12-month follow-up. Data Sources Direct contact and structured questionnaires by phone or via internet. Methods Adults (30–75 years) were included if they were smokers of ≥1 tobacco cigarette/day (tobacco smokers), users of any type of e-cigarettes, inhaling ≥50 puffs weekly (e-smokers), or smokers of both tobacco and e-cigarettes (dual smokers). Carbon monoxide levels were tested in a sample of those declaring tobacco smoking abstinence. Main Outcome Measures Sustained smoking abstinence from tobacco smoking at 12 months, reduction in the number of tobacco cigarettes smoked daily. Data Synthesis We used linear and logistic regression, with region as cluster unit. Results Follow-up data were available for 236 e-smokers, 491 tobacco smokers, and 232 dual smokers (overall response rate 70.8%). All e-smokers were tobacco ex-smokers. At 12 months, 61.9% of the e-smokers were still abstinent from tobacco smoking; 20.6% of the tobacco smokers and 22.0% of the dual smokers achieved tobacco abstinence. Adjusting for potential confounders, tobacco smoking abstinence or cessation remained significantly more likely among e-smokers (adjusted OR 5.19; 95% CI: 3.35–8.02), whereas adding e-cigarettes to tobacco smoking did not enhance the likelihood of quitting tobacco and did not reduce tobacco cigarette consumption. E-smokers showed a minimal but significantly higher increase in self-rated health than other smokers. Non significant differences were found in self-reported serious adverse events (eleven overall). Conclusions Adding e-cigarettes to tobacco smoking did not facilitate smoking cessation or reduction. If e-cigarette safety will be confirmed, however, the use of e-cigarettes alone may facilitate quitters remaining so. Registration Number NCT01785537.

In)accuracy of blood pressure measurement in 14 Italian hospitals

Objectives: The diagnosis and control of hypertension depend on accurate measurement of blood pressure (BP). The literature on the accuracy of BP recording by health professionals is, however, limited, and no study directly interviewed patients in the hospital setting. This multicenter cross-sectional study aimed at evaluating the compliance to current recommendations on BP measurement by health professionals directly from patients and to investigate potential predictors of higher quality in BP recording. Methods: A trained nurse interviewed a random sample of adult patients hospitalized for an ordinary admission (except in the emergency room) lasting more than one night, without mental disorder, who had their BP routinely measured by the hospital personnel less than 3 h before. The questionnaire contained 15 items on the main procedures that are common to current guidelines. Results: Fourteen public hospitals from seven regions of Italy participated, and 1334 questionnaires were collected. Nine of the recommended practices were followed in the majority (>70%) of BP recordings, whereas some others were infrequent or rare: in 98.6, 82.2 and 81.1% of the participants, respectively, the arm circumference was never recorded, BP was measured only once, and BP was never recorded in both arms. Overall, 10 or more recommended procedures were followed during 33.4% recordings. At multivariate analysis, physicians were less likely than nurses to provide a more accurate BP measurement. Conclusions: The operators compliance to some recommendations in BP measurement is unacceptably low. This survey provides detailed indications for medical directors on the procedures and settings to prioritize in educational programs, which are definitely needed.

Phlebitis risk varies by peripheral venous catheter site and increases after 96 hours: a large multi‐centre prospective study

AIMS This multi-centre prospective field study evaluated whether peripheral venous catheter site of insertion influences the risk of catheter-related phlebitis. Potential predictors of phlebitis were also investigated. BACKGROUND Millions of patients worldwide use peripheral venous catheters, which frequently cause local complications including phlebitis, infection and obstruction. Although phlebitis predictors have been broadly investigated, uncertainties remain on the potential effect of cannulation anatomical site, duration and the appropriate time for catheter removal. DESIGN A prospective cohort design was carried out from January-June 2012. METHODS The clinical course of each patient who received a new peripheral venous catheter for any cause in five Italian hospitals was followed by trained nurses until catheter removal. The presence of phlebitis was assessed every 24 hours using the Visual Infusion Phlebitis score. Analyses were based upon multilevel mixed-effects regression. RESULTS The final sample consisted of 1498 patients. The average time for catheters in situ was 65·6 hours and 23·6% of the catheters were in place beyond 96 hours. Overall phlebitis incidence was 15·4%, 94·4% of which were grade 1. The likelihood of phlebitis independently increased with increasing catheter duration, being highest after 96 hours. Compared with patients with catheter placed in the dorsum of the hand (22·8% of the sample), those with the catheter located in the antecubital fossa (34·1%) or forearm were less likely to have a phlebitis of any grade. CONCLUSIONS Antecubital fossa and forearm veins may be preferential sites for peripheral venous cannulation. Our results support Centers for Disease Control and Prevention recommendations to replace catheters in adults no later than 96 hours. A relevant proportion of healthcare personnel did not adhere to such guidelines - more attention to this issue is required.

Prenatal Risk Factors and Outcomes in Gastroschisis: A Meta-Analysis

BACKGROUND AND OBJECTIVE: Gastroschisis is a congenital anomaly with increasing incidence, easy prenatal diagnosis and extremely variable postnatal outcomes. Our objective was to systematically review the evidence regarding the association between prenatal ultrasound signs (intraabdominal bowel dilatation [IABD], extraabdominal bowel dilatation, gastric dilatation [GD], bowel wall thickness, polyhydramnios, and small for gestational age) and perinatal outcomes in gastroschisis (bowel atresia, intra uterine death, neonatal death, time to full enteral feeding, length of total parenteral nutrition and length of in hospital stay). METHODS: Medline, Embase, and Cochrane databases were searched electronically. Studies exploring the association between antenatal ultrasound signs and outcomes in gastroschisis were considered suitable for inclusion. Two reviewers independently extracted relevant data regarding study characteristics and pregnancy outcome. All meta-analyses were computed using individual data random-effect logistic regression, with single study as the cluster unit. RESULTS: Twenty-six studies, including 2023 fetuses, were included. We found significant positive associations between IABD and bowel atresia (odds ratio [OR]: 5.48, 95% confidence interval [CI] 3.1–9.8), polyhydramnios and bowel atresia (OR: 3.76, 95% CI 1.7–8.3), and GD and neonatal death (OR: 5.58, 95% CI 1.3–24.1). No other ultrasound sign was significantly related to any other outcome. CONCLUSIONS: IABD, polyhydramnios, and GD can be used to an extent to identify a subgroup of neonates with a prenatal diagnosis of gastroschisis at higher risk to develop postnatal complications. Data are still inconclusive on the predictive ability of several signs combined, and large prospective studies are needed to improve the quality of prenatal counseling and the neonatal care for this condition.

Prevalence of hyperandrogenic states in late adolescent and young women: epidemiological survey on italian high-school students.

CONTEXT Most of the estimates of the prevalence of hyperandrogenic states refer to the general adult population. OBJECTIVE The objective of the study was to estimate the prevalence of hyperandrogenic states in late adolescence and youth and to evaluate potential independent predictors. DESIGN This was a cross-sectional study. SETTING The study was conducted in high schools. PATIENTS Patients included female students, aged 16-19 years. MAIN OUTCOME MEASURES The study protocol was designed with 3 possible levels of participation: the first level consisted of a self-compiled questionnaire; the second level added a medical examination; and the third level added a blood sample for laboratory testing. Liquid chromatography-tandem mass spectrometry was used to measure total testosterone, and a reference interval was established in-house. RESULTS We offered participation to 2052 students, and 1469 of those compiled the questionnaire. Of these, 1038 were examined, and 519 also provided blood samples. Two hundred three of the 1038 examined students and 125 of the 519 students who provided blood samples were subsequently excluded because of treatment with oral contraceptives or because of endocrine disorders. In the sample of women with a questionnaire + a medical examination, 13% were affected by isolated menstrual irregularity, 16.1% by isolated clinical hyperandrogenism, and 3.8% by both states. A similar prevalence of isolated menstrual irregularity (10.2%) and isolated clinical hyperandrogenism (16.7%) was found in the subsample of women with laboratory tests; in addition, 6.6% showed isolated hyperandrogenemia, and 4.3% proved to be affected by polycystic ovary syndrome. CONCLUSIONS This study provides for the first time a reliable assessment of the prevalence of hyperandrogenic states in late adolescent and young females and confirms that hyperandrogenic disorders originate at a young age.

Cohort study of electronic cigarette use: Effectiveness and safety at 24 months

Objective To evaluate the safety and effectiveness of e-cigarettes, by comparing users of only e-cigarettes, smokers of only tobacco cigarettes and dual users. Design Prospective cohort study. We update previous 12-month findings and report the results of the 24-month follow-up. Data sources Direct contact and questionnaires by phone or via internet. Methods Adults (30–75 years) were classified as: (1) tobacco smokers, if they smoked ≥1 tobacco cigarette/day, (2) e-cigarette users, if they inhaled ≥50 puffs/week of any type of e-cigarette and (3) dual users, if they smoked tobacco cigarettes and also used e-cigarettes. Carbon monoxide levels were tested in 50% of those declaring tobacco smoking abstinence. Hospital discharge data were used to validate possibly related serious adverse events in 46.0% of the sample. Main outcome measures Sustained abstinence from tobacco cigarettes and/or e-cigarettes after 24 months, the difference in the number of tobacco cigarettes smoked daily between baseline and 24 months, possibly related serious adverse events. Results Data at 24 months were available for 229 e-cigarette users, 480 tobacco smokers and 223 dual users (overall response rate 68.8%). Of the e-cigarette users, 61.1% remained abstinent from tobacco (while 23.1% and 26.0% of tobacco-only smokers and dual users achieved tobacco abstinence). The rate (18.8%) of stopping use of either product (tobacco and/or e-cigarettes) was not higher for e-cigarette users compared with tobacco smokers or dual users. Self-rated health and adverse events were similar between all groups. Among those continuing to smoke, there were no differences in the proportion of participants reducing tobacco cigarette consumption by 50% or more, the average daily number of cigarettes and the average self-rated health by baseline group. Most dual users at baseline abandoned e-cigarettes and continued to smoke tobacco. Those who continued dual using or converted from tobacco smoking to dual use during follow-up experienced significant improvements in the 3 outcomes compared with those who continued or switched to only smoking tobacco (p<0.001). Conclusions E-cigarette use alone might support tobacco quitters remaining abstinent from smoking. However, dual use did not improve the likelihood of quitting tobacco or e-cigarette use, but may be helpful to reduce tobacco consumption. Adverse event data were scarce and must be considered preliminary. Trial registration number NCT01785537.

Depression symptoms and the progression of carotid intima-media thickness: a 5-year follow-up study.

OBJECTIVE Only a few studies have investigated the changes in carotid intima-media thickness (IMT) over time, and uncertainties remain on the underlying mechanisms linking depression and subclinical atherosclerosis. We carried out a prospective cohort study to evaluate whether depression is associated with changes in carotid IMT in subjects with cardiac risk factors but free from coronary heart disease (CHD), and to what extent the atherogenicity of depression can be explained by inflammatory markers and autonomic nervous system dysfunction. METHODS During baseline and follow-up visits: all participants were asked to provide blood samples and compile a structured questionnaire; trained physicians assessed depression symptoms using Beck Depression Inventory (BDI); altered cardiac autonomic tone was measured using time-domain components of heart rate variability in 24 h Holter recordings; measurements of carotid IMT were carried out using B-mode ultrasound image acquisition. Logistic and linear regression analyses were used to adjust for potential confounders and explore potential mediators. RESULTS A total of 381 subjects completed the 5-year follow-up. The mean carotid IMT significantly increased in all subjects but the amount of increase was significantly larger among subjects with depression symptoms: mean IMT increased by 0.16±0.14 mm; 0.31±0.28 mm and 0.61±0.54 mm among the subjects with no, mild and moderate/severe depression, respectively (all p<0.01). The association between moderate/severe depression and IMT increase remained highly significant even after controlling for all the variables considered, however when both IL-6 and CRP were included in multivariate models the regression coefficient decreased by 42.3%. Some of the inflammation markers and autonomic nervous system dysfunction were also independently correlated with carotid IMT increase. CONCLUSION Depression symptoms are independently associated with an accelerated progression of carotid IMT in subjects with CHD risk factors, and inflammation may substantially modulate the association between depression and carotid IMT progression.

Nonobstructive Versus Obstructive Coronary Artery Disease in Acute Coronary Syndrome: A Meta‐Analysis

Background Differences in prognosis and baseline clinical presentation have been documented among patient with acute coronary syndrome and coronary artery disease with obstructive (ObCAD) or nonobstructive arteries (NObCAD), but the rates of events largely varied across single studies. We carried out a meta‐analysis to compare the clinical presentation and prognosis of NObCAD versus ObCAD acute coronary syndrome patients, as well as of the subjects with zero versus mild occlusion. Methods and Results Searches were made in MedLine, EMBASE, Cochrane databases, and proceedings of international meetings up to June 30, 2015. We compared the risk of events of NObCAD versus ObCAD patients using random‐effect meta‐analyses. We also performed meta‐analyses to estimate the yearly or monthly outcome rates in each single group. In NObCAD and ObCAD patients, respectively, the combined yearly rates were as follows: 2.4% versus 10.1% (all‐cause mortality); 1.2% versus 6.0% (myocardial infarction), 4.0% versus 12.8% (all‐cause mortality plus myocardial infarction), 1.4% versus 5.9% (cardiac death), and 9.2% versus 16.8% (major cardiovascular events). In the studies directly comparing NObCAD versus ObCAD, all of the above outcomes were significantly less frequent in NObCAD subjects (with risk ratios ranging from 0.33 to 0.66). No differences in any outcome rate were observed between mild occlusion (1–49% stenosis) and zero occlusion patients. Conclusions NObCAD in patients with acute coronary syndrome has a significantly lower cardiovascular risk at baseline and a subsequent lower likelihood of death or main cardiovascular events. However, these subjects are still at high risk for cardiovascular mortality and morbidity, suggesting potential undertreatment and calling for specific management.

Impact of atrial fibrillation termination mode during catheter ablation procedure on maintenance of sinus rhythm

BACKGROUND Catheter ablation is a common and effective procedure for addressing atrial fibrillation (AF) refractory to antiarrhythmic drugs. AF can be terminated in 3 modes: (1) directly into sinus rhythm (SR); (2) evolving into regular atrial tachycardia (AT) and subsequently into SR; and (3) after direct current (DC) cardioversion if AF persists. Scarce data are available on the relationship between clinical outcomes and termination mode after 1 catheter ablation. OBJECTIVE The purpose of this study was to evaluate for the first time the association between 1-year ablation efficacy and termination mode after repeated catheter ablations in patients presenting with persistent or long-standing persistent AF. METHODS This prospective study involved 400 consecutive patients (age 62.7 ± 7.2 years) who underwent catheter ablation for drug-refractory persistent AF (4.6 ± 2.4 months) using a stepwise ablation approach. RESULTS AF was terminated by radiofrequency application directly into SR in 135 patients; passing through AT into SR in 195 patients; and through DC cardioversion in 70 patients. After 1-year follow-up with repeated Holter monitoring, the percentages of SR maintenance were 72.6%, 80.0%, and 28.6%, respectively (P < .001). Compared with the subjects who were converted directly into SR, the adjusted hazard ratios (HRs) of SR maintenance were significantly lower for those who required DC cardioversion (HR = 0.54; P < .001) and higher for those converted through AT (HR = 1.69; P = .027). The latter association was even stronger in the 104 subjects who required a second procedure (HR = 6.25; P = .001). CONCLUSION Termination of AF through AT during catheter ablation was more effective than both DC shock and direct SR in maintaining stable SR 1 year after both the first and the second procedures.