Factors affecting safe and healthy diet in older adults in Italy: results of a preliminary study performed in a community-dwelling sample.

OBJECTIVE: To investigate, through a questionnaire, older adults' demographic and socio-economic characteristics, knowledge, attitudes and practices in terms of food safety and healthy diet; and to develop dietary and hygiene indices able to represent participants' nutritional and food safety behaviour, exploring their association with demographic and socio-economic factors. DESIGN: One-year cross-sectional study. SETTING: Gemelli Teaching Hospital (Rome, Italy). PARTICIPANTS: People aged ≥65 years, Italian speaking, accessing the Centre of Ageing Medicine. RESULTS: Mean age of the sample was 74 (sd 7·7) years. Subjective perception of a safe diet was high: 64·2 % of respondents believed they have a balanced diet. Interviewees got informed about proper nutrition mainly from television, magazines, newspapers, Internet (29·9 %) and from health professionals (34·8 %) such as dietitians, whereas 15·4 % from general practitioners. Regarding food safety, 33·8 % of participants reported to consume expired food, even more than once per month; between 80 and 90 % of participants reported to follow food safety practices during preparation and cooking, even though 49·3 % defrosted food at room temperature. Calculated dietary and hygiene indices showed that the elderly participants were far from having optimal nutritional and food safety behaviours. CONCLUSIONS: These results suggest it is necessary to increase the awareness of older adults in the matter of healthy diet and food safety. Specific and targeted educational interventions for the elderly and their caregivers could improve the adoption of recommended food safety practices and safe nutritional behaviours among older adults.

Correction to: Recurrent pregnancy loss is associated to leaky gut: a novel pathogenic model of endometrium inflammation?

Following publication of the original article [1], the authors reported updated affiliations for five of the authors. The updated affiliations are shown below and reflected in the affiliation list of this Correction.

Recurrent pregnancy loss is associated to leaky gut: a novel pathogenic model of endometrium inflammation?

BACKGROUND: Recurrent pregnancy loss (RPL) occurs in 3-5% in about 30% of cases no cause can be found. Women with RPL show higher prevalence of undiagnosed gut disorders. Furthermore, in endometrial tissues of RPL women, higher expression of pro-inflammatory cytokines and Nalp-3 inflammasome has been observed. Aim of this study was to investigate whether an abnormal gut permeability might occur in RPL women and allow passage into systemic circulation of pro-inflammatory molecules able to induce endometrial inflammation. METHODS: 70 women with idiopathic RPL and 30 healthy women were recruited at the Recurrent Pregnancy Loss Outpatient Unit of the Gemelli Hospital of Rome from March 2013 to February 2017. Enrolled women underwent 51Cr-ethylene-diamine-tetraacetic acid absorption test to evaluate intestinal permeability. Sera obtained from enrolled women were analysed for lipopolysaccharide (LPS) by ELISA. Anxiety and depression state were evaluated by administering STAI-Y and Zung-SDS tests, respectively. Of all recruited individuals, 35 women with idiopathic RPL and 20 healthy controls accepted to undergo diagnostic hysteroscopy and endometrial biopsy. Endometrial lysates were investigated for inflammasome Nalp-3 by Western blot analysis, and caspase-1, IL-1ß and IL-18 by ELISA, respectively. RESULTS: Higher prevalence of abnormal intestinal permeability (P < 0.0001), increased circulating levels of LPS (P < 0.05), anxiety (P < 0.05) and depression (P < 0.05) were observed in RLP women compared to controls. Endometrial expression of Nalp-3, caspase-1 and IL-1ß was significantly increased in RPL group (P < 0.0001; P < 0.05 and P < 0.001, respectively). IL-18 endometrial levels were not found to be higher in RPL cases. Statistically significant association between higher intestinal permeability and abnormally increased expression of endometrial Nalp-3, was observed in RPL (P < 0.01). Furthermore, higher LPS serum levels, a bacterial-derived activator of Nalp-3 complex, was shown to be statistically associated to abnormal endometrial expression of Nalp-3 inflammasome (P < 0.01) in RPL women. CONCLUSIONS: In women with RLP, leaky gut might occur and allow passage into circulation of immune triggers, potentially able to elicit endometrial innate immune response and, thus, to contribute to miscarriage pathogenesis. Diagnosis and treatment of intestinal disorders underlying leaky gut might improve endometrial environment and pregnancy outcome.

The effect of multifactorial lifestyle interventions on cardiovascular risk factors: a systematic review and meta-analysis of trials conducted in the general population and high risk groups.

Cardiovascular diseases (CVDs) are the leading cause of premature mortality and disability accounting for one third of all deaths worldwide with considerable impacts on economics and on the quality of life. The evidence suggests that a multifactorial lifestyle intervention might have a role in the CVDs risk reduction, especially in the risk populations, nonetheless the effects on modifiable CVDs risk factors have not been completely explored. Our work aimed at evaluating the impact of multifactorial lifestyle interventions on cardiovascular risk modification, both in the general and risk population. A systematic review and meta-analysis of the randomized controlled trials (RCTs) were performed by including articles published up to April 16th, 2016. RCTs were selected if they had investigated the impact of multifactorial lifestyle interventions on lipids, blood pressure, BMI and waist circumference, smoking and physical activity. Changes in the level of modifiable risk factors from baseline were evaluated. Search resulted in 19,847 studies, of which 36 were included in the analysis. Compared to a usual care, the multifactorial lifestyle intervention is able to lower the blood pressure, total cholesterol, BMI and waist circumference, at both 6 and 12months, and to increase physical activity at 12months. Better results were obtained in primary prevention and in moderate and high risk groups. Multifactorial lifestyle interventions clearly represent a valid tool for reducing the cardiovascular risk factors and should be implemented in the risk groups and in primary prevention.

Disinvestment in healthcare: an overview of HTA agencies and organizations activities at European level.

BACKGROUND: In an era of a growing economic pressure for all health systems, the interest for "disinvestment" in healthcare increased. In this context, evidence based approaches such as Health Technology Assessment (HTA) are needed both to invest and to disinvest in health technologies. In order to investigate the extent of application of HTA in this field, methodological projects/frameworks, case studies, dissemination initiatives on disinvestment released by HTA agencies and organizations located in Europe were searched. METHODS: In July 2015, the websites of HTA agencies and organizations belonging to the European network for HTA (EUnetHTA) and the International Network of Agencies for HTA (INAHTA) were accessed and searched through the use of the term "disinvestment". Retrieved deliverables were considered eligible if they reported methodological projects/frameworks, case studies and dissemination initiatives focused on disinvestment in healthcare. RESULTS: 62 HTA agencies/organizations were accessed and eight methodological projects/frameworks, one case study and one dissemination initiative were found starting from 2007. With respect to methodological projects/frameworks, two were delivered in Austria, one in Italy, two in Spain and three in U.K. As for the case study and the dissemination initiative, both came from U.K. The majority of deliverables were aimed at making an overview of existing disinvestment approaches and at identifying challenges in their introduction. CONCLUSIONS: Today, in a healthcare context characterized by resource scarcity and increasing service demand, "disinvestment" from low-value services and reinvestment in high-value ones is a key strategy that may be supported by HTA. The lack of evaluation of technologies in use, in particular at the end of their lifecycle, may be due to the scant availability of frameworks and guidelines for identification and assessment of obsolete technologies that was shown by our work. Although several projects were carried out in different countries, most remain constrained to the field of research. Disinvestment is a relatively new concept in HTA that could pose challenges also from a methodological point of view. To tackle these challenges, it is necessary to construct experiences at international level with the aim to develop new methodological approaches to produce and grow evidence on disinvestment policies and practices.

Prevalence, molecular characterization, and clinical relevance of sensitization to Anisakis simplex in children with sensitization and/or allergy to Dermatophagoides pteronyssinus.

SUMMARY: Prevalence of the Anisakis Simplex's (AS) sensitization in children sensitized to Dermatophagoides pteronissynus (DP) is not known, neither it is to which percentage it might be due to cross-reactivity. The primary objective of the present retrospective cross-sectional study is to evaluate the prevalence of sensitization to AS in children sensitized or allergic to DP. Secondary outcomes were the prevalence of cross-reactivity and clinical relevance of the condition. The prevalence of sensitization to AS differs significantly among patients sensitized and not to DP (13.43% vs. 3.80%; p=0.019). The higher prevalence is mainly due to cross-reactivity with Der p10 (OR=8.86; 95% CI=4.33-40.74; p=0.0001). Currently, the sensitization to AS seems to have no clinical relevance in the pediatric population.

A non-invasive prevention program model for the assessment of osteoporosis in the early postmenopausal period: a pilot study on FRAX(®) and QUS tools advantages.

OBJECTIVE: The study analyses the performances of FRAX algorithm and quantitative ultrasound (QUS) tool in relationship to the dual-energy X-ray absorptiometry (DXA) categorization to identify patients at risk of osteoporosis during menopause and to reach new thresholds for recommending the first DXA examination. DESIGN: Retrospective cohort study. PATIENTS AND MEASUREMENTS: Two hundred eighty-two postmenopausal patients filled out a questionnaire which determined their FRAX index and performed a bone evaluation by QUS of the calcaneus to determine their stiffness index (SI). Thereafter, they underwent assessments by the gold-standard DXA bone examination. RESULTS: Statistically significant correlations were observed between FRAX (calculated without BMD) and both QUS and DXA diagnosis. FRAX mean indices of risk corresponding to the diagnosis of osteoporosis by QUS and DXA were similar. Receiver operating characteristic (ROC) curve analysis showed that both FRAX and QUS tests were sufficiently accurate in predicting the alteration of bone mineral composition. The ROC curves of QUS allowed us to identify, in our population, SI cutoff for normal patients (SI > 90.5) and for patients having osteoporosis (SI < 78.5). We selected a cutoff screening value from FRAX ROC curve for major clinical fracture (2.94). The following diagnostic algorithm demonstrated that the use of FRAX test alone has a sensitivity of 85.3 % and a specificity of 33.8 % while the use of QUS exam alone showed a sensitivity of 81.3 % and a specificity of 45.1 %. When considering the capacity of QUS exam in combination with FRAX test, the final algorithm showed a sensitivity of 69.4 % and a specificity of 57.7 %. CONCLUSIONS: The use of QUS test with adjusted cutoffs offers a similar performance to the FRAX test alone in terms of sensitivity. The combined use of the tests reduces the sensibility but increases the specificity and adds clinical information related to the bone status of the patient.

Knowledge, attitudes and behaviors of the Italian population towards Neisseria meningitidis, Streptococcus pneumoniae and HPV diseases and vaccinations: A cross-sectional multicentre study.

OBJECTIVES: This study addressed knowledge of Streptococcus pneumoniae, Neisseria meningitidis and human papillomavirus (HPV), and attitudes and behaviours towards vaccines against them. STUDY DESIGN: This is a cross-sectional, multicentre study. METHODS: Data were collected through a questionnaire administered to 530 adults who accessed four Departments of Prevention of the Italian National Health Service in 2013. RESULTS: Less than 50% of people gave the right answer to all the questions concerning the three diseases, but 96.2%, 94% and 92.7% agreed with the importance of vaccination against N. meningitidis, S. pneumoniae and HPV, respectively, and 58.4% expressed own willingness to have their children vaccinated with N. meningitidis B vaccine. The attitude towards vaccination was more positive in women for N. meningitidis and in people having children for HPV. Furthermore, individuals giving correct answers to all knowledge items were more in favour of both HPV and S. pneumoniae vaccination. A total of 68.8%, 82.6% and 84.5% of respondents vaccinated their own children against N. meningitidis C, S. pneumoniae and HPV, respectively. About 50% of the respondents reported paediatricians' or other health professionals' recommendations as the main reason for vaccination. CONCLUSIONS: Vaccinations may be promoted through actions aimed at increasing citizens' knowledge. Health professionals should be educated to actively provide information on vaccinations in a clear, comprehensive and effective way.

Use of DALYs in economic analyses on interventions for infectious diseases: a systematic review.

A systematic literature review was performed on full economic evaluations of infectious disease interventions using disability-adjusted life years (DALY) as outcome measure. The search was limited to the period between 1994 and September 2011 and conducted in Medline, SciSearch and EMBASE databases. We included 154 studies, mostly targeting HIV/AIDS and malaria with most conducted for African countries (40%) and <10% in high-income countries. Third-payer perspective was applied in 29% of the studies, 25% used the societal perspective and 12% used both. Only 16% of the studies took indirect effects (i.e. herd immunity) of interventions into account. Intervention, direct healthcare and indirect non-healthcare costs were taken into account in respectively 100%, 81% and 36% of the studies. The majority of the studies followed the Global Burden of Disease method for DALY estimations, but most studies deviated from WHO cost-effectiveness guidelines. Better adherence to freely accessible guidelines will improve generalizability between full economic evaluations.

Assessment of timeliness, representativeness and quality of data reported to Italy's national integrated surveillance system for acute viral hepatitis (SEIEVA).

OBJECTIVES: Periodic assessment of surveillance systems is recommended to verify whether they are appropriately monitoring the public health problem under surveillance. The aim of this study was to evaluate timeliness, data quality and representativeness of data reported to the Italian Integrated Epidemiological System for Acute Viral Hepatitis (SEIEVA). STUDY DESIGN: Cross-sectional analysis of surveillance data. METHODS: Quantitative indicators were used to evaluate representativeness of reported cases, data quality, and timeliness between surveillance steps, for reports of acute viral hepatitis cases with date of onset of symptoms from 2009 to 2012 (N = 4516). RESULTS: Representativeness was 75%. Over 95% of records reported information on age, sex, city of residence, risk factors for hepatitis A and vaccination status. Information on risk factors for hepatitis B and C were reported less consistently (83%), as was information on early outcome (60%). Wide delays were found between surveillance steps. CONCLUSIONS: The system collects high quality data on acute viral hepatitis cases in Italy. Timeliness was found to be the main limit and needs to be improved by optimizing web-based reporting procedures, increasing communication with participating centres, improving feedback and increasing dissemination of surveillance results. The study highlights the importance of reporting timeliness to detect outbreaks of acute viral hepatitis.

Systematic review of studies investigating the association between dietary habits and cutaneous malignant melanoma.

OBJECTIVE: Several papers have dealt with diet as a risk factor for cutaneous malignant melanoma (CMM). This study aimed to synthesize available data on the topic. STUDY DESIGN: A systematic review of observational studies assessing the association between dietary habits and CMM was performed. METHODS: Electronic databases were used to identify eligible articles. Quality was assessed through the Newcastle-Ottawa scale. Case-control and cohort studies evaluating the intake of food/nutrients through the assessment of dietary habits and the occurrence of CMM were considered eligible. Data comparing the highest and lowest levels of consumption were collected from single studies and described qualitatively as data combination was not possible. Results were reported as percentages on the basis of relative risks and odds ratios. RESULTS: Eighteen studies reported in 21 articles were selected. Cohort studies showed better quality than case-control studies. Most articles did not detect any significant association between food/nutrient intake and CMM, except for limited evidence of a protective role associated with fish, vegetables and fruit. Risk reduction was shown to be 35-37%, 40-57% and 34-46%, respectively, in studies reporting significant results. Similarly, few articles showed protective roles of beta-carotene and vitamins A, C, D and E, with risk reduction of 64%, 37-43%, 41%, 15-39% and 50-66%, respectively. CONCLUSION: A trend towards reduced risk of CMM associated with higher intake of fish, vegetables and fruit, as well as beta-carotene and vitamins A, C, D and E, has been shown but further research is needed to provide decisive data.

How can the results of Health Technology Assessment (HTA) evaluations applied to vaccinations be communicated to decision-makers and stakeholders? The ISPOR Rome Chapter Project.

HTA is considered the most comprehensive and transparent method of supporting decision-makers in their choices in Public Health. HTA on vaccines is being performed by many experts. However, they often present their studies to colleagues, but not to decisionmakers, who should be the main target and current users. It is therefore crucial to improve the transfer of scientific data to decision- makers and all stakeholders. The aims of the present project are: 1) to set up a team of experts to collect economic evaluations and HTA studies on vaccines and assess their actual use in decision-making processes; 2) to constitute regional working groups in order to identify the critical aspects of the communication process and identify the most appropriate method of data transfer. Systematic reviews of economic evaluations and HTA on vaccines and their actual use in decision-making will be used to draw up the basic documents for discussion by the 3 regional working boards. The working groups will discuss the current scientific evidence and communication methods and will try to implement a model of technology assessment with well-defined and objective criteria, in order to better fit pharmaco-economic and HTA methods to the field of vaccinations. Improving the transfer of HTA results to stakeholders, particularly decision-makers, will enable decisions to be taken on the basis of scientific evidence, and appropriate, sustainable actions to be undertaken.

An antibody reactivity-based assay for diagnosis of invasive candidiasis using protein array.

The increased incidence of invasive candidiasis and of patients at risk requires early diagnosis and treatment to improve prognosis and survival. The aim of this study was to set up a ten-protein array-based immunoassay to assess the IgG antibody responses against ten well-known immunogenic C. albicans proteins (Bgl2, Eno1, Pgk1, Pdc11, Fba1, Adh1, Als3, Hwp1, Hsp90 and Grp2) in 51 patients with invasive candidiasis (IC) and in 38 culture-negative controls (non-IC). Antibody levels were higher against Bgl2, Eno1, Pgk1, Als3, Hwp1 and Grp2, than against Adh1, Pdc11, Fba1 and Hsp90, irrespectively of the patient group considered. Moreover, the IgG levels against Bgl2, Eno1, Pgk1 and Grp2 were significantly higher in IC than in non-IC patients. Furthermore, the ROC curves generated by the analysis of the antibody responses against Bgl2, Grp2 and Pgk1 displayed AUC values above 0.7, thus discriminating IC and non-IC patients. According to these results, the employment of the microarray immunoassay (a rapid, sensitive and multiparametric system), in parallel with conventional diagnostics, can help to spot IC patients. This ultimately will allow to initiate an early, focused and optimized antifungal therapy.

Non steroid treatment for eczema: results from a controlled and randomized study.

AIM: This study assesses the efficacy of a new non steroid anti-inflammatory product in comparison to Hydrocortisone Butyrate 0.1% Cream in healing eczematous dermatitis. METHODS: A bilateral controlled randomized pilot study was conducted in Italian adults affected by eczema with at least two symmetric lesions at baseline, respectively assigned to a non steroid cream or Hydrocortisone. The severity of lesions was judged through the Global Clinical Score (GCS) and the recovery was defined as a GSC equal to 0. The study investigated: 1) the differences in GCS between four points in time during therapy (baseline, four, eight, twelve weeks), according to medication received; 2) treatment efficacy. RESULTS: The study showed that time, treatment and interaction between treatment and time were associated with GCS; moreover, lesions treated with Hydrocortisone went better on the whole but the post-hoc analysis showed a significant clinical improving at each point in time only for the non steroid cream. At the end of the study, in the intention to treat analysis, lesions recovered in 76.1% and 40.3% patients treated with Hydrocortisone and with the non steroid cream respectively; in the per protocol population, recovery was achieved in 91.7% and 58.3% of cases. CONCLUSION: According to the results, the non steroid cream has been demonstrated effective in reducing the severity of eczema and may be used with continuing success in the long term treatment of the disease.

Bladder function after spinal anesthesia for cesarean section: an urodynamic evaluation.

BACKGROUND: This study evaluates the effects of spinal anesthesia with hyperbaric bupivacaine plus sufentanil on bladder function in women undergoing cesarean section. SUBJECTS AND METHODS: Thirty caucasian healthy pregnants scheduled for elective Cesarean section under spinal anesthesia performed with hyperbaric bupivacaine plus sufentanil were enrolled. Filling cystometry, proprioceptive bladder sensation during cystometry, rate of spontaneous voiding, post void residual volume, anocutaneous and bulbocavernosus reflex were analyzed at 4, 6 and 8 hours after spinal anesthesia. RESULTS: The proportion of women experiencing first sensation, first desire and strong desire at 4 hours was significantly different from that reported at 6 and 8 hours (p < 0.05 for first sensation and p < 0.01 for first and strong desire). Significant differences were also observed between volumes at which first sensation arose at first measurement (4 hours) and at second and third measurements (p < 0.01). There was a significant difference in rate of spontaneous micturition, with 80% of patients at 8 hours able to spontaneously void versus 40% at 6 hours, (p < 0.01). Moreover, a lower percentage of women had absent and/or light reflexes at 4 hour than at 6 and 8 hours (p < 0.01). CONCLUSIONS: Spinal anesthesia with bupivacaine plus sufentanil causes a clinically significant disturbance on bladder function in women undergoing cesarean section. Even thought recovery of proprioceptive bladder sensation is fast, a full recovery of spontaneous voiding requires a much longer time. A close monitoring of urinary function and of bladder distension is, therefore, advisable.

Magnetic resonance imaging of solitary brain metastases: main findings of nonmorphological sequences.

PURPOSE: This study was done to investigate the usefulness of diffusion-weighted (DWI), perfusion-weighted (PWI) and proton magnetic resonance (MR) spectroscopy imaging in characterising solitary brain metastases. MATERIALS AND METHODS: Fifty-nine solitary brain metastases were evaluated with conventional and nonmorphological MR imaging: DWI, PWI and MR spectroscopy. We evaluated size, signal intensity and contrast enhancement and calculated apparent diffusion coefficient (ADC), relative cerebral blood volume (rCBV), percentage of signal intensity recovery (PSR) and maximum values of N-acetylaspartate (NAA), choline (Cho), creatine (Cr), lipids (Lip), NAA/Cr and Cho/Cr. The nonmorphological parameters were compared with those from the literature for brain lesions that frequently enter the differential diagnosis with metastases. RESULTS: Signal intensity and contrast enhancement patterns were variable. There was a wide range of ADC values: min:max 0.59×10(-3):1.88×10(-3). Compared with normal white matter, rCBV was higher in lesions (3.30±1.59) and lower in perilesional oedema (0.42±0.15). Mean and minimum PSR were 57% and 48%, respectively; lip and Cho were elevated and NAA reduced. CONCLUSIONS: Conventional MR findings of solitary metastases are heterogeneous, and some values of nonmorphological sequences are similar to those of other brain lesions. PWI seems to be the nonmorphological MR technique that may best contribute to the diagnosis of brain metastases.

Effect of pravastatin on endothelial function and endothelial progenitor cells in healthy postmenopausal women.

PURPOSE: Coronary heart disease is the leading cause of morbidity and mortality in postmenopausal women. Among statins, pravastatin has been shown to significantly reduce fatal and non-fatal cardiovascular events in primary and secondary prevention trials. The aim of the present research was to investigate whether treatment with pravastatin can modify some indices of cardiovascular risk in healthy postmenopausal women such as significant reductions in total and LDL cholesterol and triglyceride levels. METHODS: 20 patients were randomized in double-blind fashion to treatment for eight weeks with either pravastatin 40 mg/day or placebo, and subsequently, after one-week wash-out, crossed-over to the alternative treatment (placebo or pravastatin) for the following eight weeks. We performed clinical and laboratory investigations, before and at the end of each treatment period, to evaluate patient response to the treatment with pravastatin. RESULTS: After eight weeks pravastatin therapy reduced the median low density lipoprotein (LDL) and total cholesterol (p < 0.01 in both cases). In contrast, insulin level and insulin sensitivity did not show any difference with regard to values observed after placebo treatment. The absolute number of endothelial progenitor cells-colony forming unit (EPC-CFU) was significantly increased by pravastatin treatment (30.6% increase, p < 0.05) and the number of senescent cells was significantly decreased. However pravastatin did not increase tube-like formation by EPC and did not improve endothelial function. CONCLUSIONS: Despite beneficial effect on lipids and EPC, short term pravastatin does not seem to improve other cardiovascular risk factors, at least in healthy postmenopausal women.

23-valent pneumococcal polysaccharide vaccine (PPV23) for the prevention of invasive pneumococcal diseases (IPDs) in the elderly: is it really effective?

INTRODUCTION: Incidence of invasive pneumococcal diseases (IPDs) in Italy is constantly increasing and that is particularly true among the elderly. 23-valent polysaccharide pneumococcal vaccine (PPV23) is recommended to this age group and offered in all Italian regions. However, efficacy of PPV23 on preventing IPDs is debated. We therefore performed a review of the most recent available meta-analyses in order to assess the efficacy of PPVs. METHODS: The literature search was conducted using PubMed and Scopus search engines. We used the following keywords: "pneumococcal", "polysaccharide", "vaccine", "efficacy", "elderly", "meta analysis". Only meta-analyses published in the last 7 years were selected. We examined the results of the selected meta-analyses and assessed their quality according to the PRISMA recommendations. RESULTS: The search returned 16 results in PubMed and 12 in Scopus: among them we selected 3 meta-analyses. According to our quality assessment, all meta-analyses showed generally positive results and almost all items of the PRISMA checklist were respected. However, the research protocol and the registration number were absent in all the 3 revisions and the flow-chart was not shown in Moberley's and Melegaro's works. In the study by Huss et al. the relative risk of developing IPDs among vaccinated subjects was 0.90 (95%CI: 0.46-1.77, I2 4.9%), indicating a very slight benefit after vaccination. This contrasts with the results of the Cochrane Review by Moberley et al., in which the PPVs showed a protective efficacy in reducing the risk of IPDs of 74% (OR 0.26, 95% CI: 0.15-0.46) with no statistical heterogeneity (I2 0%). Melegaro et al. found a reduction not statistically significant of the incidence of IPD of 65% (OR 0.35; 95% CI 0.08-1.49) among healthy elderly, while the global estimate of vaccine efficacy among high risk elderly was minimal (OR 0.80; 95% CI 0.22-2.88). CONCLUSIONS: Most of the studies suggest that the PPVs confer low protection against IPDs. Anyhow, their methodological heterogeneity does not allow definitive conclusions. While waiting to see the results of new trials about the efficacy of PPVs, in particular of PPV23, and the extension of the use of conjugate vaccine among the population over 65, stakeholders should be aware of the results of the meta-analyses discussed in this paper during the implementation of the vaccination programs for the elderly in Public Health.

Modulation of motor cortex neuronal networks by rTMS: comparison of local and remote effects of six different protocols of stimulation.

Repetitive transcranial magnetic stimulation (rTMS) of human motor cortex can produce long-lasting changes in the excitability of excitatory and inhibitory neuronal networks. The effects of rTMS depend critically on stimulus frequency. The aim of our present study was to compare the effects of different rTMS protocols. We compared the aftereffects of 6 different rTMS protocols [paired associative stimulation at interstimulus intervals of 25 (PAS(25)) and 10 ms (PAS(10)); theta burst stimulation delivered as continuous (cTBS) or intermittent delivery pattern (iTBS); 1- and 5-Hz rTMS] on the excitability of stimulated and contralateral motor cortex in 10 healthy subjects. A pronounced increase of cortical excitability, evaluated by measuring the amplitude of motor evoked potentials (MEPs), was produced by iTBS (+56%) and PAS(25) (+45%). Five-hertz rTMS did not produce a significant increase of MEPs. A pronounced decrease of cortical excitability was produced by PAS(10) (-31%), cTBS (-29%), and 1-Hz rTMS (-20%). Short-interval intracortical inhibition was suppressed by PAS(10). Cortical silent period duration was increased by 1-Hz stimulation. No significant effect was observed in the contralateral hemisphere. Head-to-head comparison of the different protocols enabled us to identify the most effective paradigms for modulating the excitatory and inhibitory circuits activated by TMS.

Hormonal deficiencies in heart failure with preserved ejection fraction: prevalence and impact on diastolic dysfunction: a pilot study.

OBJECTIVE: In heart failure with reduced ejection fraction, catabolic mechanisms have a strong negative impact on mortality and morbidity. The relationship between anabolic hormonal deficiency, thyroid function, and heart failure with preserved ejection fraction (HFpEF) has still been poorly investigated. Therefore, we aimed to define the multi-hormonal deficiency prevalence in HFpEF patients and the relationships between hormonal deficiency and echocardiographic indexes. PATIENTS AND METHODS: Plasma levels of N-terminal pro-brain natriuretic peptide, fasting glucose, thyroid-stimulating hormone, free triiodothyronine (T3), free thyroxine, insulin-like growth factor-1, dehydroepiandrosterone-sulfate (DHEA-S), total testosterone (only in male subjects) in 40 patients with HFpEF were evaluated. An echocardiographic evaluation was performed. RESULTS: One (2.5%) patient (2.5%) had no hormonal deficiencies; 8 (20%) patients had deficits of one hormone, 18 patients (45%) of two axes, 12 patients (30%) of three axes, and one patient (2.5%) of all four axes. Among them, 97.5% had DHEA-S deficiency, 67.5% IGF-1 deficiency, 37% testosterone deficiency, 22.5% a "Low T3 syndrome", and 20% subclinical hypothyroidism. Patients with IGF-1 deficit showed higher left atrial volume values, systolic pulmonary artery pressure (SPAP), tricuspid peak velocity (TPV), and lower tricuspid annular plane systolic excursion (TAPSE) and TAPSE/SPAP ratio values. Patients with testosterone deficiency had higher SPAP and TPV. Patients with low T3 syndrome had higher value of right ventricular mid cavity diameter. Hormonal dysfunction was independent from the presence of comorbidities and no difference between male and female subjects was noted. CONCLUSIONS: Multi-hormonal deficiencies are associated with right ventricular dysfunction and diastolic dysfunction in patients with HFpEF.