Burden of healthcare-associated infections in Italy: incidence, attributable mortality and disability-adjusted life years (DALYs) from a nationwide study, 2016.

BACKGROUND: Healthcare-associated infections (HAIs) are an increasing public health threat. Measuring disease burden in disability-adjusted life-years (DALYs) allows the combination of morbidity and mortality into one figure, as it represents the summation of years lived with disability and years of life lost. AIM: To evaluate the incidence, attributable deaths and burden of the most significant HAIs in Italy. METHODS: Prevalence data from the study sample of the 2016 national Point Prevalence Survey of HAIs in acute-care settings were used to estimate the incidence of five HAIs. The methodology from the Burden of Communicable Diseases in Europe (BCoDE)-project was employed for DALY calculations, adapting the disease models to the Italian population. FINDINGS: We estimated a total of 641,065 (95% uncertainty interval, UI 585,543.00-699,207.90) new yearly cases of HAIs and 29,375 (95% UI 23,705.97-35,905.80) deaths in Italy in 2016. The total annual DALYs were estimated to be 424,657.45 (95% UI 346,240.35-513,357.28), corresponding to 702.53 DALYs (95% UI 575.22-844.66) per 100,000 general population. Bloodstream infections accounted for the majority of total DALYs (59%), healthcare-associated pneumonia for 29%, surgical site infections for 9%, CDI for 2% and urinary tract infections accounted for less than 1% of total DALYs. CONCLUSION: Results of this study suggest HAIs have a substantial burden in Italy. Reducing the burden of HAIs through infection prevention and control efforts is an achievable goal. This study provides data that could be used to guide policy-makers in the implementation of these measures.

Data quality assessment and subsampling strategies to correct distributional bias in prevalence studies.

BACKGROUND: Healthcare-associated infections (HAIs) represent a major Public Health issue. Hospital-based prevalence studies are a common tool of HAI surveillance, but data quality problems and non-representativeness can undermine their reliability. METHODS: This study proposes three algorithms that, given a convenience sample and variables relevant for the outcome of the study, select a subsample with specific distributional characteristics, boosting either representativeness (Probability and Distance procedures) or risk factors' balance (Uniformity procedure). A "Quality Score" (QS) was also developed to grade sampled units according to data completeness and reliability. The methodologies were evaluated through bootstrapping on a convenience sample of 135 hospitals collected during the 2016 Italian Point Prevalence Survey (PPS) on HAIs. RESULTS: The QS highlighted wide variations in data quality among hospitals (median QS 52.9 points, range 7.98-628, lower meaning better quality), with most problems ascribable to ward and hospital-related data reporting. Both Distance and Probability procedures produced subsamples with lower distributional bias (Log-likelihood score increased from 7.3 to 29 points). The Uniformity procedure increased the homogeneity of the sample characteristics (e.g., - 58.4% in geographical variability). The procedures selected hospitals with higher data quality, especially the Probability procedure (lower QS in 100% of bootstrap simulations). The Distance procedure produced lower HAI prevalence estimates (6.98% compared to 7.44% in the convenience sample), more in line with the European median. CONCLUSIONS: The QS and the subsampling procedures proposed in this study could represent effective tools to improve the quality of prevalence studies, decreasing the biases that can arise due to non-probabilistic sample collection.

Do HCWs adequately know about meningitis and 4CMenB vaccine and recommend its use to parents? A cross sectional analysis in Campania Region, Italy.

Invasive meningococcal disease (IMD) is a severe disease caused by various Neisseria meningitidis serogroups that represents a serious public health problem worldwide. In Italy, serogroups B and C are the major causes of IMD. On 14 January 2013, the European Medicines Agency authorized the use of the first vaccine available to protect against meningococcal serogroup B (4CMenB). The aim of this study was to assess the IMD epidemiology knowledge and 4CMenB vaccine attitudes of healthcare workers (HCWs) with regard to recommending this vaccine for use, vaccine practices and infectious disease control in the Campania region in Italy. A cross-sectional study was conducted among 293 HCWs (49.5% physicians and 46.4% nurses)interviewed using a self-administered questionnaire. The majority of the HCWs had sufficient knowledge about the disease incidence and lethality, but they were less informed about the higher risk age categories and the serogroups most frequently involved. Additionally, their knowledge about the vaccine was poor with regard to the targeted categories and side effects. Approximately30.0% of the HCWs reported incidences of fever and pain and swelling at the injection site. Moreover,32.8% of the HCWs knew that the risk of developing adverse reactions increases when the 4CMenB vaccine is co-administered with other vaccines. Overall, all of the HCWs were convinced that vaccinations are an important instrument for preventing infectious diseases, and they were aware of their central role in promoting the 4CmenB vaccination and their need to be better informed.

The influence of ovulation induction and assisted conception on maternal and perinatal outcomes of twin pregnancies.

OBJECTIVE: To compare obstetrical and neonatal outcomes of twin pregnancies conceived via assisted reproductive technology (ART) with those of naturally conceived ones and to investigate the influence of the ART procedure type on these parameters. PATIENTS AND METHODS: This observational study included 450 ART and 647 spontaneous twin pregnancies delivered over 15 years at a single university-based hospital of Rome, Italy. Logistic and linear regression models adjusted for confounding factors were used to evaluate the effect of ART and the type of assisted conception (IVF/ICSI, ovulation induction ± intrauterine insemination, egg/embryo donation) on maternal and perinatal outcomes. RESULTS: The mean gestational age was significantly lower in pregnancies conceived via ART. The occurrence rates of gestational diabetes, antenatal admission, prophylactic administration of corticosteroid, very preterm delivery and neonatal intensive care unit admission were higher in the ART group. Twin pregnancies achieved via egg/embryo donation had a lower risk of maternal thrombocytopenia and cervical incompetence and were at greater risk of receiving corticosteroid prophylaxis and patent ductus arteriosus than pregnancies obtained by IVF/ICSI. Conception by ovulation induction was associated with reduced risk of hyperemesis gravidarum and longer neonatal hospitalization compared to pregnancies obtained by IVF/ICSI. CONCLUSIONS: Assisted conception was associated with adverse obstetrical outcomes and lower gestational age, but after adjustment for gestational age neonatal immediate outcomes were similar to those observed in the spontaneous group. There were no many important differences in the outcomes of twin pregnancies obtained by a different type of conception.

Ankle fusion in hemophilic patients.

INTRODUCTION: Hemophilic arthropathy is painful and disabling. We report a retrospective study of ankle fusion with intra- and peri-operative clotting factor perfusion. The objective was to assess the efficacy of maintaining perioperative clotting factor rates close to 100%, and report long-term results. The study hypothesis was that results would be good, without early hemorrhagic complications. MATERIAL AND METHOD: Between 2000 and 2013, 12 ankle fusions were performed in 9 patients, with a mean age of 39years (range, 19-58years). Anti-hemophilic factor perfusion was controlled by the reference physician of the Regional Hemophilia Treatment Center. Clinical AOFAS and Olerud scores and the Pettersson radiologic score were used for assessment. Mean preoperative AOFAS score was 22 (range, 2-55) and mean Olerud score 7 (range, 5-12). Mean preoperative factor VIII concentration was <1% (range, <1-3%). RESULTS: Mean follow-up was 8years (range, 2-16years). Mean AOFAS score at follow-up was 69 (range, 35-92) and mean Olerud score 70 (range, 30-100). Improvement mainly concerned the Pain dimension. Statistical analysis found a significant difference between pre- and post-operative clinical scores (AOFAS, P=0.004; Olerud, P=0.004). Mean factor VIII concentration at surgery was 90% (range, 24-117%), and 109% (range, 75-152%) the day following surgery. There were no cases of hematoma or surgical site infection. Radiologic fusion was systematic at a mean 3.5 months (range, 3-4months). CONCLUSION: The study hypothesis was confirmed. Ankle fusion in advanced hemophilic arthropathy improved function and quality of life. Perioperative clotting factor perfusion contributed to these good results, providing supplementary prevention of hemorrhagic risk. LEVEL OF EVIDENCE: IV, retrospective study.

Total knee arthroplasty after opening- versus closing-wedge high tibial osteotomy. A 135-case series with minimum 5-year follow-up.

INTRODUCTION: High tibial osteotomy (HTO) is effective in treating isolated medial osteoarthritis of the knee, but subsequent deterioration is inevitable, and total knee arthroplasty (TKA) is then an option. The present study sought to compare TKA following medial opening-wedge HTO (OW-HTO) versus lateral closing-wedge HTO (CW-HTO) in terms of intraoperative data and clinical results. The study hypothesis was that there is no significant difference in clinical results or complications in TKA following OW-HTO or CW-HTO. MATERIAL AND METHOD: A retrospective multicenter (9 centers) study was conducted for the French Society of Orthopedic Surgery and Traumatology (SoFCOT), including 135 TKAs following HTO (58 OW and 77 CW) at a minimum 5 years' follow-up. Mean interval between HTO and TKA was 134 months and was longer in case of CW-HTO (P<0.0001). Mean age at TKA was 65.4 years and older in case of CW-HTO (P=0.021). Tibial slope was greater in case of OW-HTO (P=0.024). Prior to TKA, 55.7% of patients could walk without canes, 98.4% found stairs difficult or impossible and only 19.1% could manage a walking distance greater than 1000m. Mean flexion was 110°; 54.2% of patients showed frontal knee stability and 87.8% sagittal stability; 60.1% had a mechanical axis in varus, without difference according to OW- or CW-HTO. RESULTS: Hardware was almost systematically removed (in 98.5% of cases): in the same step for OW-HTO (P=0.018) or often in 2 steps for CW-HTO. The primary approach was generally re-used (54.2%), but less frequently in the CW-HTO group (P=0.0004). Lateral or medial ligament release was not associated in respectively 78.2% and 79.7% of cases. The TKA implant was usually without stem (87.2%) and was fitted using a conventional technique (74.4%). At a mean 87 months' follow-up, 78.5% of patients could walk without canes, stairs were still difficult or impossible for 67%, and 74.1% could now walk further than 1000m; mean flexion was 110.5°. Overall, 91.5% of patients showed frontal knee stability and 98.2% sagittal stability, without difference according to OW- or CW-HTO. There were 15 complications within 3 months, more often in the OW-HTO group (12.3%) although not significantly, and with no difference in severity. Late complications comprised loosening (5.5%) and infection (3.6%) and were more frequent in the CW-HTO group (12%) (P<0.05). DISCUSSION: The study hypothesis was partially confirmed. The only technical differences concerned hardware removal, often performed in two steps in case of CW-HTO, and TKA approach, which differed from the primary approach in case of CW-HTO. Clinical results were comparable between OW- and CW-HTO, but late complications were more frequent in the CW-HTO group. LEVEL OF EVIDENCE: III; comparative retrospective study.

Cervical carcinogenesis, bacterial vaginosis, HPV-mRNA test and relapse of CIN2+ after loop electrosurgical excision procedure (LEEP).

OBJECTIVE: The aim of the study was to evaluate the relationship between bacterial vaginosis (BV) and relapse of cervical intraepithelial neoplasia grade 2 or more (CIN2+) after Loop electrosurgical excision procedure (LEEP). PATIENTS AND METHODS: One hundred four patients who underwent LEEP for CIN2+ were followed up every six months for three years. Fifty-three were negative for BV and fifty-one were positive. Each clinical control included Pap test, colposcopy, Amsel criteria test, HPV-DNA, and HPV-mRNA test. RESULTS: Patients' age, presence of BV, positivity to HPV-DNA and HPV-mRNA tests were analyzed. The average age of patients was 42.5 ± 8.92 years (median: 42.5; range from 27 to 58 years). The minimum follow-up was 6 months and maximum 36 months (average: 22.8 ± 4.53; median: 24). The 10% of the patients with HPV-mRNA test negative had relapsed, compared to 45% of patients with HPV-mRNA test positive. Among the 53 patients without BV the 20% had relapsed compared with 23% of 51 patients with diagnosis of BV. CONCLUSIONS: There is no evidence for higher percentage of relapse in patients with BV, submitted to excisional procedure for CIN2+ associated to HPV-m-RNA test positivity. There is only a correlation among BV and relapse of CIN2+ lesions after LEEP.

Detection of penetration of the dorsal cortex by epiphyseal screws of distal radius volar plates: Anatomical study comparing ultrasound and fluoroscopy.

HYPOTHESIS: Osteosynthesis of the distal radius by a volar plate can be complicated by lesions of extensor tendons by screws penetrating the dorsal cortex. The fluoroscopic skyline view enables to confirm the length of the screws. To avoid its risk of irradiation, some authors have recommended using ultrasound instead. MATERIAL AND METHODS: The goal of this study was to demonstrate that the detection rate of screws penetrating the dorsal cortex was at least as good using ultrasound compared to fluoroscopic skyline. A volar plate in which one screw penetrated the dorsal cortex was implanted in 10 cadaveric wrists. Three observers had to detect which screw penetrated the dorsal cortex using ultrasound and then a fluoroscopic skyline. RESULTS: The detection rate of screws penetrating the dorsal cortex was 43.33% with ultrasound and 96.97% using the fluoroscopic skyline. Agreement between the observers was poor with ultrasound and good with fluoroscopy. CONCLUSION: Our results show that ultrasound cannot replace the fluoroscopic skyline view to detect screws penetrating the dorsal cortex of the distal radius in clinical practice. LEVEL OF EVIDENCE: II.

Default mode network changes in multiple sclerosis: a link between depression and cognitive impairment?

BACKGROUND AND PURPOSE: In multiple sclerosis (MS), depression is a common disorder whose pathophysiology is still debated. To gain insights into the pathophysiology of depression in MS, resting-state (RS) functional connectivity (FC) changes of the default mode network (DMN), salience network (SN) and executive control network (ECN) were assessed in a group of depressed MS (D-MS) patients and in appropriately matched control groups. METHODS: Sixteen D-MS patients, 17 non-depressed MS (ND-MS) patients, 17 non-depressed healthy controls and 15 depressed subjects (D-S), age, sex and education matched, cognitively preserved and non-fatigued, were enrolled. All participants underwent a neuropsychological evaluation and RS functional magnetic resonance imaging study. RESULTS: Comparing D-MS patients with D-S, within the DMN, a significant RS-FC suppression was found in the posterior cingulate cortex (PCC); comparing D-MS with ND-MS, FC was significantly increased in the anterior cingulate cortex and significantly reduced in the PCC. Within the SN increased FC in the right supramarginal gyrus and right middle frontal gyrus was found in D-MS patients compared to D-S and to ND-MS; within the ECN increased FC in the right inferior parietal cortex was found in D-MS patients compared to ND-MS patients. CONCLUSIONS: In cognitively preserved D-MS patients, FC derangement occurs in the SN, ECN and DMN. In the latter, changes occurring both in the anterior cingulate cortex and PCC suggest that depression in MS may be linked to MS itself and, in particular, to a peculiar pattern of network abnormalities favored by MS pathology through disconnection mechanisms. Reduced FC in the PCC, similar to MS patients with cognitive impairment, suggests a functional link between depression and cognitive impairment in MS.

NOD-SCID mice irradiation with medical accelerators: Dosimetric and radiobiological results.

PURPOSE: Preclinical studies normally requires dedicated instruments due to the small anatomical scales involved, but the possibility of using clinical devices for this purpose may be of economical, scientific and translational interest. In the present work the accurate description of treatment planning, dosimetric results, radiotoxicity and tumor response of the irradiation of NOD-SCID mice were presented. Two medical linear accelerators, TrueBeam STx and Tomotherapy Hi-ART, were compared. NOD-SCID mice irradiation with Tomotherapy is a novelty, as well as the comparison of different irradiation techniques, devices and dose fractionations. METHODS: Human derived glioblastoma multiforme neurospheres were injected in immunocompromised NOD-SCID mice to establish xenograft models. Mice were anaesthetized and placed in a plexiglas cage pieboth to perform CT scan for treatment planning purposes and for the irradiation. Three fractionation schedules were evaluated: 4Gy/1 fraction, 4Gy/2 fractions and 6Gy/3 fractions. Tomotherapy planning parameters, the presence of a bolus layer and the irradiation time were reported. After irradiation, mice were examined daily and sacrificed when they showed signs of suffering or when tumor volume reached the established endpoint. Outcomes regarding both radiotoxicity and tumor response were evaluated comparing irradiated mice as respect to their controls. RESULTS: Survival analysis showed that Tomotherapy irradiation with 6Gy/3 fractions with a bolus layer prolong mice survival (log-rank test, p<0.02). Tumor volume and mice survival were significantly different in irradiated xenografts as compared to their controls (t-test, p<0.03; log-rank, p<0.05). CONCLUSION: The radiobiological potential of Tomotherapy in inducing tumor growth stabilization is demonstrated.

Depressive Symptoms Correlate with Disability and Disease Course in Multiple Sclerosis Patients: An Italian Multi-Center Study Using the Beck Depression Inventory.

BACKGROUND: Depression occurs in about 50% of patients with multiple sclerosis. The aims of this study was to investigate the prevalence of depressive symptoms in a multicenter MS population using the Beck Depression Inventory II (BDI II) and to identify possible correlations between the BDI II score and demographic and clinical variables. METHODS: Data were collected in a multi-center, cross-sectional study over a period of six months in six MS centers in Italy using BDI II. RESULTS: 1,011 MS patients participated in the study. 676 subjects were female, with a mean age of 34 years (SD 10.8), mean EDSS of 3.3 (0-8.5) and mean disease duration of 10.3 years (range 1-50 years). 668 (%) subjects scored lower than 14 on the BDI II and 343 (33.9%) scored greater than 14 (14 cut-off score). For patients with BDI>14 multivariate analysis showed a significant difference between EDSS and disease course. BDI II scores for subjects with secondary progressive (SP) MS were significantly different from primary progressive (PP) patients (p < 0.001) but similar to relapsing-remitting (RR) patients. Considering subjects with moderate to severe depressive symptoms (BDI II score from 20-63), in relation to disease course, 11.7% (83/710) had RR MS, 40.7% (96/236) SP and 13.6% (6/44) PP. CONCLUSIONS: Using the BDI II, 30% of the current sample had depressive symptoms. BDI II score correlates with disability and disease course, particularly in subjects with SP MS. The BDI II scale can be a useful tool in clinical practice to screen depressive symptoms in people with MS.

Psychometric properties and validity of Beck Depression Inventory II in multiple sclerosis.

BACKGROUND AND PURPOSE: Depression is the most common psychiatric disorder in multiple sclerosis (MS). Self-report depression scales are frequently used as screening, diagnostic and grading instruments. This study investigated the psychometric properties of the Beck Depression Inventory second edition (BDI-II) for assessing depressive disorders in a sample of Italian MS patients. METHODS: The sample included 141 consecutive non-demented MS patients who completed the BDI-II and the Chicago Multiscale Depression Inventory (CMDI). MS patients also completed a clinical interview, a neurological/neuropsychological examination and a Fatigue Severity Score (FSS) questionnaire in order to assess divergent validity. RESULTS: The BDI-II showed good internal consistency (Cronbach's alpha 0.89) and good convergent and divergent validity. With respect to CMDI serving as the 'gold standard', the receiver operating characteristic curve revealed that BDI-II is an adequate diagnostic measure and that the optimum total cut-off score was 18.5. Such score identified clinically relevant depressive symptoms in 25.5% of our MS sample. CONCLUSIONS: The BDI-II is a simple, reliable and valid tool for detecting and grading depressive symptoms in Italian MS patients.

Cognitive impairment and memory disorders in relapsing-remitting multiple sclerosis: the role of white matter, gray matter and hippocampus.

Cognitive disorders occur in up to 65 % of multiple sclerosis (MS) patients; they have been correlated with different MRI measures of brain tissue damage, whole and regional brain atrophy. The hippocampal involvement has been poorly investigated in cognitively impaired (CI) MS patients. The objective of this study is to analyze and compare brain tissue abnormalities, including hippocampal atrophy, in relapsing-remitting MS (RRMS) patients with and without cognitive deficits, and to investigate their role in determining cognitive impairment in MS. Forty-six RRMS patients [20 CI and 26 cognitively preserved (CP)] and 25 age, sex and education-matched healthy controls (HCs) underwent neuropsychological evaluation and 3-Tesla anatomical MRI. T2 lesion load (T2-LL) was computed with a semiautomatic method, gray matter volume and white matter volume were estimated using SIENAX. Hippocampal volume (HV) was obtained by manual segmentation. Brain tissues volumes were compared among groups and correlated with cognitive performances. Compared to HCs, RRMS patients had significant atrophy of WM, GM, left and right Hippocampus (p < 0.001). Compared to CP, CI RRMS patients showed higher T2-LL (p = 0.02) and WM atrophy (p = 0.01). In the whole RRMS group, several cognitive tests correlated with brain tissue abnormalities (T2-LL, WM and GM atrophy); only verbal memory performances correlated with left hippocampal atrophy. Our results emphasize the role of T2-LL and WM atrophy in determining clinically evident cognitive impairment in MS patients and provide evidence that GM and hippocampal atrophy occur in MS patients regardless of cognitive status.

Computer-aided cognitive rehabilitation improves cognitive performances and induces brain functional connectivity changes in relapsing remitting multiple sclerosis patients: an exploratory study.

To better understand the effects of short-term computer-based cognitive rehabilitation (cCR) on cognitive performances and default mode network (DMN) intrinsic functional connectivity (FC) in cognitively impaired relapsing remitting (RR) multiple sclerosis (MS) patients. Eighteen cognitively impaired RRMS patients underwent neuropsychological evaluation by the Rao's brief repeatable battery and resting-state functional magnetic resonance imaging to evaluate FC of the DMN before and after a short-term (8 weeks, twice a week) cCR. A control group of 14 cognitively impaired RRMS patients was assigned to an aspecific cognitive training (aCT), and underwent the same study protocol. Correlations between DMN and cognitive performances were also tested. After cCR, there was a significant improvement of the following tests: SDMT (p < 0.01), PASAT 3" (p < 0.00), PASAT 2" (p < 0.03), SRT-D (p < 0.02), and 10/36 SPART-D (p < 0.04); as well as a significant increase of the FC of the DMN in the posterior cingulate cortex (PCC) and bilateral inferior parietal cortex (IPC). After cCR, a significant negative correlation between Stroop Color-Word Interference Test and FC in the PCC emerged. After aCT, the control group did not show any significant effect either on FC or neuropsychological tests. No significant differences were found in brain volumes and lesion load in both groups when comparing data acquired at baseline and after cCR or aCT. In cognitively impaired RRMS patients, cCR improves cognitive performances (i.e., processing speed and visual and verbal sustained memory), and increases FC in the PCC and IPC of the DMN. This exploratory study suggests that cCR may induce adaptive cortical reorganization favoring better cognitive performances, thus strengthening the value of cognitive exercise in the general perspective of building either cognitive or brain reserve.

Abnormalities of the thyroid in survivors of childhood Hodgkin's disease.

AIM: The progress made in the treatment of Hodgkin's disease (HD) has resulted in long-term survival rates >90%, therefore late sequelae of treatment, especially endocrine diseases, have become more important. Hypothyroidism is the most frequent thyroid disease but hyperthyroidism, thyroid nodules and cancer are also frequent. Thyroid cancer begins to appear 5-10 years after neck irradiation and risk persists for decades. Therefore it is important a careful and long-term follow-up of these patients. METHODS: This report analyzed the thyroid function of thirteen patients successfully treated for childhood HD according to three different protocols of therapy. Treatment modalities were correlated to the occurrence of thyroid dysfunction. RESULTS: After a median follow-up of 8.3 years, nine out of thirteen patients were found to have thyroid abnormalities. Six patients developed hypothyroidism, one patient developed hyperthyroidism, two patients showed only ultrasound abnormalities. CONCLUSIONS: The patients treated with lower radiotherapy (RT) doses and restricted RT extension showed a lower incidence of thyroid abnormalities compared to patients treated with higher RT dose and extended RT field. This study, even though performed in a small cohort of patients, confirms the high incidence of thyroid abnormalities in patients treated for HD and strengthens the importance of a long-term follow-up.

Frontotemporal cortical thinning in amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: The extensive application of advanced MR imaging techniques has undoubtedly improved our knowledge of the pathophysiology of amyotrophic lateral sclerosis. Nevertheless, the precise extent of neurodegeneration throughout the central nervous system is not fully understood. In the present study, we assessed the spatial distribution of cortical damage in amyotrophic lateral sclerosis by using a cortical thickness measurement approach. MATERIALS AND METHODS: Surface-based morphometry was performed on 20 patients with amyotrophic lateral sclerosis and 18 age- and sex-matched healthy control participants. Clinical scores of disability and disease progression were correlated with measures of cortical thickness. RESULTS: The patients with amyotrophic lateral sclerosis showed a significant cortical thinning in multiple motor and extramotor cortical areas when compared with healthy control participants. Gray matter loss was significantly related to disease disability in the left lateral orbitofrontal cortex (P = .04), to disease duration in the right premotor cortex (P = .007), and to disease progression rate in the left parahippocampal cortex (P = .03). CONCLUSIONS: Cortical thinning of the motor cortex might reflect upper motor neuron impairment, whereas the extramotor involvement seems to be related to disease disability, progression, and duration. The cortical pattern of neurodegeneration depicted resembles what has already been described in frontotemporal dementia, thereby providing further structural evidence of a continuum between amyotrophic lateral sclerosis and frontotemporal dementia.

Clinical and magnetic resonance imaging predictors of disease progression in multiple sclerosis: a nine-year follow-up study.

OBJECTIVE: The objective of this paper is to identify clinical or magnetic resonance imaging (MRI) predictors of long-term clinical progression in a large cohort of multiple sclerosis (MS) patients. METHODS: A total of 241 relapsing-remitting (RR) MS patients were included in a nine-year follow-up (FU) study. The reference MRIs were acquired at baseline (BL) as part of a multicenter, cross-sectional, clinical-MRI study. Volumetric MRI metrics were measured by a fully automated, operator-independent, multi-parametric segmentation method. Clinical progression was evaluated as defined by: conversion from RR to secondary progressive (SP) disease course; progression of Expanded Disability Status Scale (EDSS); achievement and time to reach EDSS 4. RESULTS: We concluded that conversion from RR to SP (OR 0.79; CI 0.7-0.9), progression of EDSS (OR 0.85; CI 0.77-0.93), achievement of EDSS 4 (OR 0.8; CI 0.7-0.9), and time to reach EDSS 4 (HR 0.88; CI 0.82-0.94) were all predicted by BL gray matter (GM) volume and, except for progression of EDSS, by BL EDSS (respectively: (OR 2.88; CI 1.9-4.36), (OR 2.7; CI 1.7-4.2), (HR 3.86; CI 1.94-7.70)). CONCLUSIONS: BL GM volume and EDSS are the best long-term predictors of disease progression in RRMS patients with a relatively long and mild disease.

The anaesthetic and recovery profile of two concentrations (0.25% and 0.50%), of intrathecal isobaric levobupivacaine for combined spinal-epidural (CSE) anaesthesia in patients undergoing modified Stark method caesarean delivery: a double blinded randomized trial.

BACKGROUND: In spinal anaesthesia for a Caesarean delivery, it is important to limit anaesthesia only at the surgical area, and to resolve fast motor block. We compared the intraoperative effectiveness, hemodynamic effects, anaesthetic recovery times and patients satisfaction after isobaric levobupivacaine (L) 0.25% versus L0.50% spinal anaesthesia during elective Caesarean deliveries performed with the Stark technique. PATIENTS AND METHODS: In this double-blinded prospective study, seventy women undergoing elective caesarean delivery were randomized to receive either intrathecal 7.5 mg Levobupivacaine 0.25% plus sufentanil 2.5 µg (Group L0.25), or intrathecal 7.5 mg L 0.50% plus sufentanil 2.5 µg (GroupControl). The onset time, duration of anaesthesia, analgesia and sensory and motor block and hemodynamic parameters were measured from the beginning of spinal anaesthesia until four hours after spinal anaesthesia (T240). RESULTS: Onset time, duration of anaesthesia and haemodynamic variations were similar in the two groups. No patients required general anesthesia to complete surgery. Motor block vanished faster in Group L0.25 as compared with GroupControl (p < .01). The cephalad spread of the 0.50% solution was higher than that of the 0.25% solution: no patient in Group L0.25 experienced paresthesia of the upper limbs vs 14% in GroupControl (p < .05). In GroupControl anaesthesia reached the dermatome T1 in 15% of cases. Maternal and surgeon satisfaction was good in every patient. CONCLUSIONS: Levobupivacaine 7.5 milligrams at 0.25% may be used as a suitable alternative to L 0.50% for spinal anaesthesia for caesarean deliveris with the Stark technique with good maternal satisfaction. In Group L0.25 a lower appearance of nausea and hypotension were observed and motor and sensitive block developed and diminished faster while no clinically significant differences in hemodynamic behavior was observed between groups.

Implementation of epidural analgesia for labor: is the standard of effective analgesia reachable in all women? An audit of two years.

BACKGROUND: Social and cultural factors combined with little information may prevent the diffusion of epidural analgesia for pain relief during childbirth. The present study was launched contemporarily to the implementation of analgesia for labor in our Department in order to perform a 2 years audit on its use. The goal is to evaluate the epidural acceptance and penetration into hospital practice by women and care givers and safety and efficacy during childbirth. PATIENTS AND METHODS: This audit cycle measured epidural analgesia performance against 4 standards: (1) Implementation of epidural analgesia for labor to all patients; (2) Acceptance and good satisfaction level reported by patients and caregivers. (3) Effectiveness of labor analgesia; (4) No maternal or fetal side effects. RESULTS: During the audit period epidural analgesia increased from 15.5% of all labors in the first trimester of the study to 51% in the last trimester (p < 0.005). Satisfaction levels reported by patients and care givers were good. A hierarchical clustering analysis identified two clusters based on VAS (Visual Analogue Scale) time course: in 226 patients (cluster 1) VAS decreased from 8.5±1.4 before to 4.1±1.3 after epidural analgesia; in 1002 patients (cluster 2) VAS decreased from 8.12±1.7 before (NS vs cluster 1), to 0.76±0.79 after (p < 0.001 vs before and vs cluster 2 after). No other differences between clusters were observed. CONCLUSIONS: Present audit shows that the process of implementation of labor analgesia was quick, successful and safe, notwithstanding the identification of one cluster of women with suboptimal response to epidural analgesia that need to be further studies, overall pregnant womens'adhesion to labor analgesia was satisfactory.

Does the metabolic syndrome predict subclinical atherosclerotic damage in an asymptomatic population at intermediate cardiovascular risk?

BACKGROUND AND AIMS: It is not clear whether the metabolic syndrome (MetS) is a distinct entity or a combination of risk factors. Several studies showed the association between MetS and cardiovascular disease (CVD). Subclinical target organ damage (TOD) is a recognized marker of atherosclerosis and predictor of cardiovascular events. Increased burden of subclinical atherosclerosis was detected in individuals with MetS. We thus aimed to examine the association between MetS and cumulative or specific TOD and to assess whether MetS predicts TOD better than the risk factors included in current definitions. METHODS AND RESULTS: We recorded TOD in 979 patients at intermediate cardiovascular risk with and without MetS according to IDF and NCEP criteria. We measured common carotid intima-media thickness, left ventricular mass index (LVMI), urine albumin to creatinine ratio (UACR), and ankle-brachial index. We found no correlation between having at least one TOD and being positive for MetS. A high UACR was associated with MetS using both IDF and NCEP criteria, while only NCEP identified individuals with increased LVMI. Using a multivariate logistic regression model including MetS, age, sex, waist circumference, triglycerides, HDL cholesterol, blood pressure and blood glucose levels we found no correlations between the presence of MetS and at least one TOD. The associations with high UACR and LVMI disappeared when age, blood pressure and glycemia were counted in. CONCLUSION: Although MetS showed some relation with subclinical renal and cardiac damage, it does not predict TOD any better than the risk factors specified in the definitions.