Comparison of Reduced-Dose Prasugrel and Standard-Dose Clopidogrel in Elderly Patients With Acute Coronary Syndromes Undergoing Early Percutaneous Revascularization.

BACKGROUND: Elderly patients are at elevated risk of both ischemic and bleeding complications after an acute coronary syndrome and display higher on-clopidogrel platelet reactivity compared with younger patients. Prasugrel 5 mg provides more predictable platelet inhibition compared with clopidogrel in the elderly, suggesting the possibility of reducing ischemic events without increasing bleeding. METHODS: In a multicenter, randomized, open-label, blinded end point trial, we compared a once-daily maintenance dose of prasugrel 5 mg with the standard clopidogrel 75 mg in patients >74 years of age with acute coronary syndrome undergoing percutaneous coronary intervention. The primary end point was the composite of mortality, myocardial infarction, disabling stroke, and rehospitalization for cardiovascular causes or bleeding within 1 year. The study was designed to demonstrate superiority of prasugrel 5 mg over clopidogrel 75 mg. RESULTS: Enrollment was interrupted, according to prespecified criteria, after a planned interim analysis, when 1443 patients (40% women; mean age, 80 years) had been enrolled with a median follow-up of 12 months, because of futility for efficacy. The primary end point occurred in 121 patients (17%) with prasugrel and 121 (16.6%) with clopidogrel (hazard ratio, 1.007; 95% confidence interval, 0.78-1.30; P=0.955). Definite/probable stent thrombosis rates were 0.7% with prasugrel versus 1.9% with clopidogrel (odds ratio, 0.36; 95% confidence interval, 0.13-1.00; P=0.06). Bleeding Academic Research Consortium types 2 and greater rates were 4.1% with prasugrel versus 2.7% with clopidogrel (odds ratio, 1.52; 95% confidence interval, 0.85-3.16; P=0.18). CONCLUSIONS: The present study in elderly patients with acute coronary syndromes showed no difference in the primary end point between reduced-dose prasugrel and standard-dose clopidogrel. However, the study should be interpreted in light of the premature termination of the trial. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01777503.

n-3 polyunsaturated fatty acids in the prevention of atrial fibrillation recurrences after electrical cardioversion: a prospective, randomized study.

BACKGROUND: n-3 polyunsaturated fatty acids (n-3 PUFAs) exert antiarrhythmic effects and reduce sudden cardiac death. However, their role in the prevention of atrial fibrillation remains controversial. We aimed to determine the effect of n-3 PUFAs in addition to amiodarone and a renin-angiotensin-aldosterone system inhibitor on the maintenance of sinus rhythm after direct current cardioversion in patients with persistent atrial fibrillation. METHODS AND RESULTS: We conducted a randomized, double-blind, placebo-controlled, parallel-arm trial in patients with persistent atrial fibrillation, with at least 1 relapse after cardioversion, and treated with amiodarone and a renin-angiotensin-aldosterone system inhibitor. Participants were assigned to placebo or n-3 PUFAs 2 g/d and then underwent direct current cardioversion 4 weeks later. The primary end point was the probability of maintenance of sinus rhythm at 1 year after cardioversion. Of 254 screened patients, 199 were found to be eligible and randomized. At the 1-year follow up, the probability of maintenance of sinus rhythm was significantly higher in the n-3 PUFAs-treated patients compared with the placebo group (hazard ratio, 0.62 [95% confidence interval, 0.52 to 0.72] and 0.36 [95% confidence interval, 0.26 to 0.46], respectively; P=0.0001). CONCLUSIONS: In patients with persistent atrial fibrillation on amiodarone and a renin-angiotensin-aldosterone system inhibitor, the addition of n-3 PUFAs 2 g/d improves the probability of the maintenance of sinus rhythm after direct current cardioversion. Our data suggest that n-3 PUFAs may exert beneficial effects in the prevention of atrial fibrillation recurrence. Further studies are needed to confirm and expand our findings. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01198275.

Impact of hemoglobin levels at admission on outcomes among elderly patients with acute coronary syndrome treated with low-dose Prasugrel or clopidogrel: A sub-study of the ELDERLY ACS 2 trial.

Hemoglobin (Hb) levels have emerged as a useful tool for risk stratification and the prediction of outcome after myocardial infarction. We aimed at evaluating the prognostic impact of this parameter among patients in advanced age, where the larger prevalence of anemia and the higher rate of comorbidities could directly impact on the cardiovascular risk. METHODS: All the patients in the ELDERLY-2 trial, were included in this analysis and stratified according to the values of hemoglobin at admission. The primary endpoint of this study was cardiovascular mortality within one year. The secondary endpoints were all-cause mortality, MI, Bleeding Academic Research Consortium (BARC) type 2-3 or 5 bleeding, any stroke, re-hospitalization for cardiovascular event or stent thrombosis (probable or definite) within 12 months after index admission. RESULTS: We included in our analysis 1364 patients, divided in quartiles of Hb values (<12.2; 12.2-13.39; 13.44-14.49; ≥ 4.5 g/dl). At a mean follow- up of 330.4 ± 99.9 days cardiovascular mortality was increased in patients with lower Hb (HR[95%CI] = 0.76 [0.59-0.97], p = 0.03). Results were no more significant after correction for baseline differences (adjusted HR[95%CI] = 1.22 [0.41-3.6], p = 0.16). Similar results were observed for overall mortality. At subgroup analysis, (according to Hb median values) a significant interaction was observed only with the type of antiplatelet therapy, but not with major high-risk subsets of patients. CONCLUSIONS: Among elderly patients with acute coronary syndrome managed invasively, lower hemoglobin at admission is associated with higher cardiovascular and all-cause mortality and major ischemic events, mainly explained by the higher risk profile.

Asymptomatic neurocognitive disorders in patients infected by HIV: fact or fiction?

Neurocognitive disorders are emerging as a possible complication in patients infected with HIV. Even if asymptomatic, neurocognitive abnormalities are frequently detected using a battery of tests. This supported the creation of asymptomatic neurocognitive impairment (ANI) as a new entity. In a recent article published in BMC Infectious Diseases, Magnus Gisslén and colleagues applied a statistical approach, concluding that there is an overestimation of the actual problem. In fact, about 20% of patients are classified as neurocognitively impaired without a clear impact on daily activities. In the present commentary, we discuss the clinical implications of their findings. Although a cautious approach would indicate a stricter follow-up of patients affected by this disorder, it is premature to consider it as a proper disease. Based on a review of the data in the current literature we conclude that it is urgent to conduct more studies to estimate the overall risk of progression of the asymptomatic neurocognitive impairment. Moreover, it is important to understand whether new biomarkers or neuroimaging tools can help to identify better the most at risk population. Please see related article: http://www.biomedcentral.com/1471-2334/11/356.

Long-term CD4+ T-cell count evolution after switching from regimens including HIV nucleoside reverse transcriptase inhibitors (NRTI) plus protease inhibitors to regimens containing NRTI plus non-NRTI or only NRTI.

BACKGROUND: Data regarding CD4+ recovery after switching from protease inhibitor (PI)-based regimens to regimens not containing PI are scarce. METHODS: Subjects with virological success on first-PI-regimens who switched to NNRTI therapy (NNRTI group) or to nucleoside reverse transcriptase (NRTI)-only (NRTI group) were studied. The effect of the switch on the ongoing CD4+ trend was assessed by two-phase linear regression (TPLR), allowing us to evaluate whether a change in the CD4+ trend (hinge) occurred and the time of its occurrence. Furthermore, we described the evolution of the frequencies in CD4-count classes across four relevant time-points (baseline, before and immediately after the switch, and last visit). Finally, we explored whether the CD4+ counts evolved differently in patients who switched to NNRTI or NRTI-only regimens by considering: the overall CD4+ trends, the time to CD4+≥ 500/mm3 after the switch, and the area-under-the-curve (AUC) of the CD4+ after the switch. RESULTS: Eight hundred and ninety-six patients, followed for a median of 2,121 days, were included. At TPLR, hinges occurred in 581/844 (68.9%), but in only 40/581 (6.9%) within a time interval (180 days) compatible with a possible relationship to the switch; furthermore, in 19/40 cases, CD4+ counts appeared to decrease after the hinges. In comparison with the NNRTI group, the NRTI group showed CD4+ count greater at baseline (P = 0.0234) and before the switch (P ≤ 0.0001), superior CD4+ T-cell increases after HAART was started, lower probability of not achieving CD4+ ≥ 500/mm3 (P = 0.0024), and, finally, no significant differences in the CD4+ T-cell AUC after the switch after adjusting for possible confounders (propensity score and pre-switch AUC). Persistence at CD4+ < 200/mm3 was observed in 34/435 (7.5%) patients, and a decrease below this level was found in only 10/259 (3.9%) with baseline CD4+ ≥ 350/mm3. CONCLUSIONS: Switching from first-line PI to NNRTI- or NRTI-based regimens did not seem to impair CD4+ trend over long-term follow-up. Although the greater CD4+ increases in patients who switched to the NRTI-only regimen was due to higher CD4+ counts before the switch, several statistical analyses consistently showed that switching to this regimen did not damage the ongoing immune-reconstitution. Lastly, the observation that CD4+ T-cell counts remained low or decreased in the long term despite virological success merits further investigation.

[Early interruption of a clinical trial: rationale and interpretation]. / Interruzione anticipata delle sperimentazioni cliniche: razionale e interpretazione.

Early interruption of a clinical trial is not a rare case, and it may be due to several reasons that are summarized in the present article. It is important for the clinician, the primary user of the information derived from clinical trials, to be able to assess whether the eventual interruption of the trial had been planned in the study protocol, whether the study organization was such as to correctly monitor the accrual of efficacy and safety data, who took the decision to interrupt the trial, whether the study patients have been exposed to excessive risks and, finally, whether the conclusions of the study report are valid. In most cases, these issues are carefully assessed during the review process of the study publication (and, of course, by the regulatory authorities) but, particularly for the studies interrupted for "overwhelming evidence of benefit", wisdom and prudence are mandatory, and the results must be considered within the context of all available evidence.

Determinants of bone damage: An ex-vivo study on porcine vertebrae.

Bone's resistance to fracture depends on several factors, such as bone mass, microarchitecture, and tissue material properties. The clinical assessment of bone strength is generally performed by Dual-X Ray Photon Absorptiometry (DXA), measuring bone mineral density (BMD) and trabecular bone score (TBS). Although it is considered the major predictor of bone strength, BMD only accounts for about 70% of fragility fractures, while the remaining 30% could be described by bone "quality" impairment parameters, mainly related to tissue microarchitecture. The assessment of bone microarchitecture generally requires more invasive techniques, which are not applicable in routine clinical practice, or X-Ray based imaging techniques, requiring a longer post-processing. Another important aspect is the presence of local damage in the bony tissue that may also affect the prediction of bone strength and fracture risk. To provide a more comprehensive analysis of bone quality and quantity, and to assess the effect of damage, here we adopt a framework that includes clinical, morphological, and mechanical analyses, carried out by means of DXA, µCT and mechanical compressive testing, respectively. This study has been carried out on trabecular bones, taken from porcine trabecular vertebrae, for the similarity with human lumbar spine. This study confirms that no single method can provide a complete characterization of bone tissue, and the combination of complementary characterization techniques is required for an accurate and exhaustive description of bone status. BMD and TBS have shown to be complementary parameters to assess bone strength, the former assessing the bone quantity and resistance to damage, and the latter the bone quality and the presence of damage accumulation without being able to predict the risk of fracture.

Natural history of hepatitis B and C in renal allograft recipients.

BACKGROUND: In renal allograft recipients, most cases of liver dysfunction are caused by hepatitis B virus and hepatitis C virus (HCV). The natural history of hepatitis C and B was studied in 286 renal allograft recipients who received a kidney allograft between 1972 and 1989 when tests for anti-HCV became available. METHODS: In all patients, hepatitis B (HB) surface (s) antigen (Ag) was tested before and anti-HCV (by enzyme-linked immunosorbent assay II) after transplantation. RESULTS: At enrollment in 1989 (5.5+/-4 years after transplantation), 209 patients were anti-HCV positive (C+), 42 patients were HBsAg-positive (B+), and 35 patients were both B+ and C+ (C+B+). One hundred four patients were receiving azathioprine (AZA) and 182 were on cyclosporine A (CsA). Since transplantation, the median follow-up was 18 years in AZA-treated and 13 years in CsA-treated patients. Liver biopsy showed chronic hepatitis in 73 patients, cirrhosis in 20 patients, and fibrosing cholestatic hepatitis in 2 patients. In 34 patients, liver biopsy was repeated, and progression of fibrosis was observed in 24 patients. The 12-year patient survival rate was similar in B+, C+, and B+C+ patients (67%, 78%, and 71%, respectively; P=not significant). Liver-related death was the first cause of death in B+ and B+C+ infected patients (58% and 72%, respectively), whereas cardiovascular disease was the leading cause of death in C+ patients (40%). Multivariate analysis showed that older age (>40 years) (relative risk [RR], 2.8), B+ status (RR, 2.36), and C+ status (RR, 1.65) were independently associated with a worse patient survival. CONCLUSIONS: In the long term, B+ patients had a higher risk of death related to liver disease than C+ patients, and co-infection did not worsen patient survival.

Urinary sediment features in proliferative and non-proliferative glomerular diseases.

BACKGROUND: The studies on urine sediment particles in patients with glomerular diseases (GD) are few and have focused only on single urine particles. In this study, we investigated the prevalence and number of 12 urine sediment particles in two groups of patients, one with proliferative GD, and the other with non-proliferative GD. METHODS: The urine sediment of 100 consecutive patients, with a renal biopsy-proven proliferative or non-proliferative GD and marked cylindruria, were examined a few hours before renal biopsy according to a standardized method. The urine particles investigated were erythrocytes, leukocytes, renal tubular cells, lipids and hyaline, hyaline-granular, granular, waxy, erythrocytic, leukocytic, epithelial and fatty casts. RESULTS: Patients with proliferative GD (n=52) had both a significantly higher prevalence of microscopic hematuria, leukocyturia, tubular epithelial cells, erythrocytic casts, epithelial casts, and significantly higher amounts of erythrocytes,leukocytes, tubular epithelial cells/20 high power field (HPF), erythrocytic and epithelial casts. On the other hand, patients with non-proliferative GD (n=48) had significantly higher numbers of fatty casts. In proliferative GD, leukocyturia was associated with intracapillary and extracapillary proliferation, crescents and fibrinoid necrosis at renal biopsy. At discriminant analysis, the two types of GD could be identified with 80.8% sensitivity and 79.2% specificity. By multiple logistic regression analysis, patients with erythrocytes, leukocytes and erythrocytic casts in the urine had an odds ratio (OR) of 9.91 (95% confidence interval (95% CI): 1.01-97.51), 7.85 (95% CI: 2.77-22.20), and 4.33 (95% CI: 1.41-13.31), respectively, of having proliferative GD. CONCLUSIONS: Our examination of the urine sediment shows that proliferative GD and non-proliferative GD differ in many respects.

Variability of specific airway resistance in patients with laryngeal hemiplegia.

OBJECTIVES: This study was designed to analyze whether respiratory flows and specific airway resistance (sRaw) depend on the degree of breathiness and on the position of the paralyzed vocal fold in laryngeal hemiplegia. METHODS: We performed a prospective study involving 55 patients affected by laryngeal hemiplegia. RESULTS: The paralyzed fold was in an intermediate position in 18 cases and in a paramedian position in 37. Breathiness was estimated with the GRBAS scale, and the patients were divided into four groups: B0 (12 patients), B1 (14), B2 (16), and B3 (13). Spirometry was used to measure the flow-volume loop, and body plethysmography was used to measure the sRaw at increasing respiratory frequencies (30 +/- 5, 60 +/- 5, and 90 +/- 5 breaths per minute). The mean inspiratory flows (PIF, FIF50) were lower than predicted (<80%) in all four groups; there was no significant intergroup difference. In all four groups, the mean FEF5o/FIF50 ratio was >1, as is typical of variable extrathoracic obstruction. The mean sRaw values increased with respiratory frequency, and the increase was higher in group B3, although the values varied widely. The frequency-dependent increase in the sRaw value was not significantly related to the degree of breathiness, nor to the position of the paralyzed fold. Furthermore, Spearman's coefficient did not reveal any correlation between the sRaw values and inspiratory flows, showing that plethysmography and spirometry explore different aspects of airway function. CONCLUSIONS: Respiratory flows and sRaw are not significantly influenced by either the degree of breathiness or the position of the paralyzed vocal fold.

Effect of kidney transplantation on bone mass and body composition in males.

BACKGROUND: Bone loss is a frequent and well-known complication in the first months after renal transplantation, but there are no data considering body composition variables (bone, fat, and lean mass) together in transplant recipients. This prospective study investigated total body bone density, fat mass, and lean mass before and 1, 2, 3, 4, and 6 months after renal transplantation in male patients who underwent hemodialysis. METHODS: Twenty consecutive renal transplant male patients aged 23-64 years (mean, 40 years; median, 41 years) received one of two immunosuppressive therapies (cyclosporine+methylprednisolone, or cyclosporine+methylprednisolone+azathioprine). The bone, fat, and lean mass of the total body and its related subregions were assessed by means of dual X-ray photon absorptiometry. Mixed factorial analysis of variance for repeated measurements was used for the statistical analysis. RESULTS: During the 6 months after transplantation, there was a reduction in trabecular bone mass in the spine, ribs, and pelvis total body subregions; the reduction was statistically significant in the last two subregions. There was no statistically significant difference in the lean mass of the total body or its subregions over time, but there was a statistically significant increase in the fat mass of the total body and all of its subregions; the increase in total and trunk fat mass seemed to be greater in the patients not receiving azathioprine. CONCLUSIONS: Up to 6 months after renal transplantation in male patients who underwent hemodialysis, there is a marked increase in fat mass, a significant loss of trabecular bone mass, and no change in cortical bone and lean mass.

Oxidative stress in kidney transplant patients.

BACKGROUND: Little information is available about the role of oxidative stress in renal transplant patients. To evaluate the prevalence and severity of oxidative stress in renal transplantation, the authors conducted a cross-sectional study. METHODS: In 112 cadaver or living-donor kidney transplant recipients with a follow-up of at least 6 months and with plasma creatinine less than or equal to 2.5 mg/dL, complete blood count, serum vitamin B12, serum folate (s-F), reactive oxygen species (ROS), thiol groups (-SH), total antioxidant activity (TAOC), serum homocysteine (Hcy), and intraerythrocyte folate (ery-F) were measured. RESULTS: The mean levels of Hcy (21.1 microM vs. <10 microM), ROS (302.7 U. Carr (Carratelli units) vs. 250-300 U. Carr), and TAOC (410.6 micromol/HclO/mL vs. >350 micromol/HclO/mL), were higher than the reference interval, whereas -SH groups, vitamin B12, s-F, and ery-F were within the normal range. In the multivariate model, plasma creatinine (P=0.0062), vitamin B12 (P=0.0121), and TAOC (P=0.0007) were independently associated with oxidative stress. At multiple regression analysis, -SH groups and ROS were directly and inversely related to hematocrit (P=0.0007 and P=0.0073). There was also a negative correlation between -SH groups and blood pressure levels (P=0.0095). CONCLUSIONS: Renal transplant patients have a pattern of increased oxidant stress that is counterbalanced by an enhancement of the antioxidant mechanisms. Besides the well-known risk factors, the authors found that anemia is an independent risk factor for an increase of ROS. Further studies are needed to evaluate whether the correction of anemia might prevent or reduce the oxidative stress in renal transplant patients.

Association between p53 gene mutations and tobacco and alcohol exposure in laryngeal squamous cell carcinoma.

OBJECTIVES: To analyze the relationship between p53 gene mutations, tobacco smoke, and alcohol consumption in patients with laryngeal squamous cell carcinoma. DESIGN: We analyzed p53 gene mutations in exons 5 through 8 by polymerase chain reaction-single-strand conformation polymorphism analysis in a cohort of 84 patients with laryngeal squamous cell carcinoma. SETTING: University hospital. RESULTS: p53 gene mutations were detected in 24 (28.6%) cases (95% confidence interval, 19.3%-39.5%), and the GC to TA transversion (33%) was the most common type of mutation (95% confidence interval, 15.6%-55.3%). Most mutations mapped to the p53 DNA-binding domain, which is necessary for the physiological activity of p53 as a tumor suppressor. A statistically significant association was found between p53 mutations and exposure to tobacco smoke (P=.001), which was the only variable significantly associated with p53 mutations in a multivariate model. The association with alcohol consumption was only at a borderline level of significance (P=.065). CONCLUSION: Our data document that a smoking habit is the only independent variable associated with an increased risk of p53 mutations in the laryngeal mucosa.

Spirometric and plethysmographic assessment of upper airway obstruction in laryngeal hemiplegia.

Laryngeal hemiplegia (LH) is the most common disorder of laryngeal motility. It is deemed not to cause obstruction of the upper airway; in fact, the main symptoms are dysphonia and breathiness, and respiratory impairment is not commonly reported. The aim of this study was to objectively assess upper airway patency in 41 patients affected by LH (mean age, 54.4 +/- 15.2 years; 27 female) and 30 controls (mean age, 50.0 +/- 16.1 years; 19 female) by means of flow-volume loop spirometry and body plethysmography to measure specific airway resistance (sRaw) at increasing respiratory frequencies. The causes of LH were cervical surgery (28), tumor infiltration (5), and unexplained (8). None of the patients or controls was affected by lower airway disease. Spirometry showed that the patients had inspiratory flows (PIF, FIF50) significantly lower than those of the controls (p < .0001), whereas the expiratory flows (FEV1, FEF50) were normal, with the exception of peak expiratory flow (PEF), which was reduced, especially in female patients. The mean FEF50/FIF50 ratio (about unity in the normal subjects) was >1, as is typical of variable extrathoracic obstruction. Plethysmography showed that the values of sRaw of the LH group were not statistically different from those of the controls at 30 +/- 5 breaths per minute, but they progressively and significantly increased at 60 +/- 5 (p < .01) and 90 +/- 5 breaths per minute (p < .002), whereas no significant sRaw change was observed in the controls. These results show that LH causes obstruction of the upper airway that can be assessed and quantified by means of spirometry and body plethysmography. A dynamic narrowing due to inspiratory medialization of the paralytic vocal fold and flow turbulence during hyperventilation seem to be the causes of patency impairment. The flow-volume loop is an excellent, inexpensive, and easily available means of functionally evaluating upper airway obstruction, but some patients have difficulty in performing an inspiratory test that requires maximal effort, and the flow reduction during forced ventilation may be partially due to the effort dependency of the tests themselves. Plethysmographic assessment of airway resistance may be a valid alternative or complement, as it reveals an increase in sRaw at increasing respiratory frequencies.

Impact of gluten-free diet on cardiovascular risk factors. A retrospective analysis in a large cohort of coeliac patients.

BACKGROUND: Concerns have been raised on whether a gluten-free diet affects the cardiovascular risk profile of coeliac patients. AIMS: To assess changes of multiple cardiovascular risk factors in coeliac patients evaluated before and during a gluten-free diet. METHODS: Retrospective analysis of the effects of 1-5 years of gluten-free diet on indicators of cardiovascular risk and on distribution in cardiovascular risk categories in 715 coeliac patients. RESULTS: Compared to baseline, significant increases were found in body mass index (21.4±3.4 vs. 22.5±3.5; p<0.0001), total cholesterol (171.2±37.4mg/dL vs. 181.4±35.1mg/dL; p<0.0001), and γ-glutamyl transpeptidase (16.5±14.9 vs. 19.5±19.2U/L; p<0.0001). Significant reductions were found in serum triglycerides (87.9±49.5 vs. 80.2±42.8mg/dL; p<0.0001) and homocysteine (16.9±9.6 vs. 13.3±8.0µmol/L; p=0.018) during gluten-free diet. The proportion of patients included in an arbitrarily defined category of "lowest cardiovascular risk profile" decreased from 58% at baseline to 47% during gluten-free diet. CONCLUSIONS: A gluten-free diet significantly affects cardiovascular risk factors in coeliac patients, but changes do not consistently point towards worse or better risk profiles, thus suggesting that the diet is unlikely to be atherogenic.

Predictors of cognitive and functional improvement and normalization after cognitive remediation in patients with schizophrenia.

OBJECTIVE: Although the efficacy of cognitive remediation interventions has been demonstrated in several experimental studies on schizophrenia, few studies have investigated the predictors of response to such interventions. We were interested in determining what factors contribute to a positive outcome after cognitive rehabilitation and whether different factors are associated with different degrees of improvement in cognitive and real-world functioning in individual patients after cognitive remediation. METHODS: The study sample consisted of 56 patients with schizophrenia who had completed a 6-month cognitive remediation intervention and showed different cognitive and functional outcomes. Measures of cognitive and functional amelioration after cognitive remediation were analyzed in relation to patients' clinical, neuropsychological and functional variables at baseline using logistic regression analysis. RESULTS: Lower antipsychotic intake at baseline predicted cognitive improvement, whereas lower antipsychotic intake, severity of specific symptoms, and higher neurocognitive functioning (particularly executive functions and verbal memory) at baseline were associated with cognitive normalization after remediation treatment. Functional improvement was predicted by lower patient age and type of cognitive remediation intervention, whereas functional normalization was related to lower baseline antipsychotic intake and, at a trend level, to higher executive functioning and type of cognitive remediation intervention. CONCLUSION: Cognitive remediation could be more effective in younger, less disorganized, and cognitively less impaired patients, who take a smaller amount of antipsychotics. The predictive role of lower antipsychotic dosage on cognitive and functional outcome after remediation suggests either that patients with less severe illness could gain better advantage from cognitive remediation interventions or that high dose or complex antipsychotic therapy may limit the effectiveness of such interventions.

Evidence of cross-reactive immunity to 2009 pandemic influenza A virus in workers seropositive to swine H1N1 influenza viruses circulating in Italy.

BACKGROUND: Pigs play a key epidemiologic role in the ecology of influenza A viruses (IAVs) emerging from animal hosts and transmitted to humans. Between 2008 and 2010, we investigated the health risk of occupational exposure to swine influenza viruses (SIVs) in Italy, during the emergence and spread of the 2009 H1N1 pandemic (H1N1pdm) virus. METHODOLOGY/PRINCIPAL FINDINGS: Serum samples from 123 swine workers (SWs) and 379 control subjects (Cs), not exposed to pig herds, were tested by haemagglutination inhibition (HI) assay against selected SIVs belonging to H1N1 (swH1N1), H1N2 (swH1N2) and H3N2 (swH3N2) subtypes circulating in the study area. Potential cross-reactivity between swine and human IAVs was evaluated by testing sera against recent, pandemic and seasonal, human influenza viruses (H1N1 and H3N2 antigenic subtypes). Samples tested against swH1N1 and H1N1pdm viruses were categorized into sera collected before (n. 84 SWs; n. 234 Cs) and after (n. 39 SWs; n. 145 Cs) the pandemic peak. HI-antibody titers ≥10 were considered positive. In both pre-pandemic and post-pandemic peak subperiods, SWs showed significantly higher swH1N1 seroprevalences when compared with Cs (52.4% vs. 4.7% and 59% vs. 9.7%, respectively). Comparable HI results were obtained against H1N1pdm antigen (58.3% vs. 7.7% and 59% vs. 31.7%, respectively). No differences were found between HI seroreactivity detected in SWs and Cs against swH1N2 (33.3% vs. 40.4%) and swH3N2 (51.2 vs. 55.4%) viruses. These findings indicate the occurrence of swH1N1 transmission from pigs to Italian SWs. CONCLUSION/SIGNIFICANCE: A significant increase of H1N1pdm seroprevalences occurred in the post-pandemic peak subperiod in the Cs (p<0.001) whereas SWs showed no differences between the two subperiods, suggesting a possible occurrence of cross-protective immunity related to previous swH1N1 infections. These data underline the importance of risk assessment and occupational health surveillance activities aimed at early detection and control of SIVs with pandemic potential in humans.