Impact of different follow-up regimens on health-related quality of life and costs in endometrial cancer patients: Results from the TOTEM randomized trial.

PURPOSE: To investigate whether intensive follow-up (INT) after surgery for endometrial cancer impact health-related quality of life (HRQoL) and healthcare costs compared to minimalist follow-up (MIN), in the absence of evidence supporting any benefit on 5-year overall survival. METHODS: In the TOTEM trial, HRQoL was assessed using the SF-12 and the Psychological General Well-Being (PGWB) questionnaires at baseline, after 6 and 12 months and then annually up to 5 years of follow-up. Costs were analyzed after 4 years of follow-up from a National Health Service perspective, stratified by risk level. The probability of missing data was analyzed for both endpoints. RESULTS: 1847 patients were included in the analyses. The probability of missing data was not influenced by the study arms (MIN vs INT OR: 0.97 95%CI: 0.87-1.08). Longitudinal changes in HRQoL scores did not differ between the two follow-up regimens (MIN vs INT SF-12 PCS: -0.573, CI95%: -1.31; 0.16; SF-12 MCS: -0.243, CI95%: -1.08; 0.59; PGWB: -0.057, CI95%: -0,88; 0,77). The mean cost difference between the intensive and minimalist arm was €531 for low-risk patients and €683 for high-risk patients. CONCLUSION: In the follow-up of endometrial cancer after surgery, a minimalist treatment regimen did not affect quality of life and was cost-saving in both low-risk and high-risk recurrence patients. As previous results showed no survival benefit, a minimalist approach is justified. The relevant proportion of missing data on secondary outcomes of interest could be a critical point that deserves special attention.

Cross-cultural validity and reliability of the comprehensive assessment of acceptance and commitment therapy processes (CompACT) in people with multiple sclerosis.

PURPOSE: The Comprehensive assessment of Acceptance and Commitment Therapy (CompACT) is a 23-item questionnaire measuring psychological flexibility, a quality of life protective factor. An 18-item version was recently produced. We assessed validity and reliability of CompACT, and equivalence of paper and electronic (eCompACT) versions in people with multiple sclerosis (PwMS) in Italy, Germany and Spain. METHODS: We used confirmatory factor analysis and assessed CompACT-23 and CompACT-18 measurement invariance between the three language versions. We assessed construct validity (Spearman's correlations) and internal consistency (Cronbach's alpha). Test-retest reliability (intraclass correlation coefficient, ICC) and equivalence of paper and eCompACT (ICC and linear regression model for repeated measures) were assessed in subsamples of PwMS. RESULTS: A total of 725 PwMS completed the study. The three-factor structure of the CompACT-23 showed poor fit (RMSEA 0.07; CFI 0.82; SRMR 0.08), while the fit of the CompACT-18 was good (RMSEA 0.05; CFI 0.93; SRMR 0.05). Configural and partial metric invariance were confirmed, as well as partial scalar invariance (reached when five items were allowed to vary freely). The CompACT-18 showed good internal consistency (all alpha ≥ 0.78); and test-retest reliability (all ICCs ≥ 0.86). Equivalence between paper and eCompACT was excellent (all ICCs ≥ 0.86), with no mode, order, or interaction effects. CONCLUSION: Results support using the refined CompACT-18 as a three-factor measure of psychological flexibility in PwMS. Paper and eCompACT-18 versions are equivalent. CompACT-18 can be used cross-culturally, but sub-optimal scalar invariance suggests that direct comparison between the three language versions should be interpreted with caution.

Influence of cognition on the correlation between objective and subjective upper limb measures in people with multiple sclerosis.

BACKGROUND: A comprehensive assessment of upper limb (UL) function is mandatory in people with multiple sclerosis (PwMS), and the use of multiple objective and subjective measures is advisable. Findings on the role of cognitive impairment on the assessment of UL function are scant and inconclusive. The present study investigated the influence of cognitive function on the distribution of objective and subjective UL measures and on their association. METHODS: In the cross-sectional study, subjects with a diagnosis of MS, age ≥ 18 years, right-hand dominance, no presence of orthopedic UL impairment, or other neurological diseases were recruited. The assessment protocol included the Nine-Hole Peg Test (9-HPT), Box and Block Test (BBT), and hand grip strength (HGS), a validated PROM (MAM-36), and the Symbol Digit Modalities Test (SDMT). RESULTS: Two hundred forty-six PwMS were recruited (158 females, mean age = 51.65 ± 13.45 years; mean EDSS = 5.10 ± 1.88) Subject with mild-to-moderate cognitive impairment (SDMT ≤ - 2 SD of normative values) scored lower on the 9-HPT and higher on the BBT and MAM-36 when compared with subject with no cognitive impairment. Cognitive impairment showed a small but significant effect on the association between 9-HPT scores and the MAM-36. DISCUSSION: Findings suggest that cognitive impairment is associated with subjects' performance on 9-HPT, BBT, and MAM-36 (but not HGS), resulting in scores indicating a poorer UL function. Interestingly, cognitive impairment slightly affected the congruence between subjective and objective UL measures, although only minor differences in the correlation pattern across groups reporting different cognitive performances emerged.

Correlation between patient-reported manual ability and three objective measures of upper limb function in people with multiple sclerosis.

BACKGROUND AND PURPOSE: Upper limb (UL) function is often affected in people with multiple sclerosis (PwMS) and is typically assessed through objective measures, including the Nine Hole Peg Test (9-HPT), Box and Block Test (BBT), and Hand Grip Strength (HGS). It is important to include the subjective perspective of PwMS in the assessment. This study aims to evaluate associations between Manual Ability Measure-36 (MAM-36) and 9-HPT, BBT, and HGS in MS. METHODS: The cross-sectional study included five Italian centers. Inclusion criteria were age ≥ 18 years, MS diagnosis, and stable disease course. Exclusion criteria were bilateral UL paralysis, and concomitant orthopedic or neurological diseases. RESULTS: A total of 199 PwMS were included: 128 female, mean age = 50.7 ± 13.0 years, 119 relapsing-remitting MS (RRMS), 31 primary and 49 secondary progressive MS, mean disease duration = 14.0 ± 10.4, years, mean Expanded Disability Status Scale (EDSS) = 4.6 ± 2.0. The MAM-36 showed small correlations with 9-HPT, BBT, and HGS. Correlations between MAM-36 and 9-HPT and BBT were highest among subjects with EDSS ≥ 6 and progressive MS. MAM-36 and HGS showed the highest correlations in subjects with EDSS ≤ 5 and RRMS. Combining 9-HPT and HGS provided the strongest predictive power over the MAM-36. CONCLUSIONS: Correlations between objective measures and MAM-36 were small to moderate, meaning that objective measures do not match subjects' perception of UL function. The combination of 9-HPT and HGS measures can help improve the assessment of UL function in activities of daily living.

Applying multidimensional computerized adaptive testing to the MSQOL-54: a simulation study.

BACKGROUND: The Multiple Sclerosis Quality of Life-54 (MSQOL-54) is one of the most commonly-used MS-specific health-related quality of life (HRQOL) measures. It is a multidimensional, MS-specific HRQOL inventory, which includes the generic SF-36 core items, supplemented with 18 MS-targeted items. Availability of an adaptive short version providing immediate item scoring may improve instrument usability and validity. However, multidimensional computerized adaptive testing (MCAT) has not been previously applied to MSQOL-54 items. We thus aimed to apply MCAT to the MSQOL-54 and assess its performance. METHODS: Responses from a large international sample of 3669 MS patients were assessed. We calibrated 52 (of the 54) items using bifactor graded response model (10 group factors and one general HRQOL factor). Then, eight simulations were run with different termination criteria: standard errors (SE) for the general factor and group factors set to different values, and change in factor estimates from one item to the next set at < 0.01 for both the general and the group factors. Performance of the MCAT was assessed by the number of administered items, root mean square difference (RMSD), and correlation. RESULTS: Eight items were removed due to local dependency. The simulation with SE set to 0.32 (general factor), and no SE thresholds (group factors) provided satisfactory performance: the median number of administered items was 24, RMSD was 0.32, and correlation was 0.94. CONCLUSIONS: Compared to the full-length MSQOL-54, the simulated MCAT required fewer items without losing precision for the general HRQOL factor. Further work is needed to add/integrate/revise MSQOL-54 items in order to make the calibration and MCAT performance efficient also on group factors, so that the MCAT version may be used in clinical practice and research.

Prediction of mortality and major cardiovascular complications in type 2 diabetes: External validation of UK Prospective Diabetes Study outcomes model version 2 in two European observational cohorts.

AIM: To externally validate the UK Prospective Diabetes Study Outcomes Model version 2 (UKPDS-OM2) by comparing the predicted and observed outcomes in two European population-based cohorts of people with type 2 diabetes. MATERIALS AND METHODS: We used data from the Casale Monferrato Survey (CMS; n = 1931) and a subgroup of the Hoorn Diabetes Care System (DCS) cohort (n = 5188). The following outcomes were analysed: all-cause mortality, myocardial infarction (MI), ischaemic heart disease (IHD), stroke, and congestive heart failure (CHF). Model performance was assessed by comparing predictions with observed cumulative incidences in each cohort during follow-up. RESULTS: All-cause mortality was overestimated by the UKPDS-OM2 in both the cohorts, with a bias of 0.05 in the CMS and 0.12 in the DCS at 10 years of follow-up. For MI, predictions were consistently higher than observed incidence over the entire follow-up in both cohorts (10 years bias 0.07 for CMS and 0.10 for DCS). The model performed well for stroke and IHD outcomes in both cohorts. CHF incidence was predicted well for the DCS (5 years bias -0.001), but underestimated for the CMS cohort. CONCLUSIONS: The UKPDS-OM2 consistently overpredicted the risk of mortality and MI in both cohorts during follow-up. Period effects may partially explain the differences. Results indicate that transferability is not satisfactory for all outcomes, and new or adjusted risk equations may be needed before applying the model to the Italian or Dutch settings.

Response shift in health-related quality of life measures in the presence of formative indicators.

BACKGROUND: Response shift (RS) has been defined as a change in the meaning of an individual's self-evaluation that needs to be accounted for when assessing longitudinal changes in health-related quality of life (HRQoL). RS detection through structural equation modeling is accomplished by adopting Oort's procedure based on a measurement model in which the observed variables are defined as reflective indicators of the HRQoL latent variable; that is, the latent variable causes the variation in the reflective indicators. This study aims to propose a procedure that assesses RS when formative indicators are used in measuring HRQoL; in this last case, the latent variable is considered to be a function of some formative indicators. A secondary aim is to compare the new procedure with Oort's procedure to highlight similarities and differences. METHODS: The data were retrieved from a consecutive series of 258 patients newly diagnosed with colorectal cancer and undergoing chemotherapy and/or surgery. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QOL-C30) was administered twice, once before and once six months after treatment. Structural equation modeling was used to evaluate RS and true change with the newly proposed method (in which fatigue and pain were defined as formative indicators) and with Oort's procedure (in which fatigue and pain were defined as reflective indicators). RESULTS: According to the new procedure, there was no measurement bias, and on average, patients' quality of life improved by 3.53 points (on a scale ranging from 0 to 100) at the 6-month follow-up. With Oort's procedure, the loading of the pain indicator was not invariant across the two time points, suggesting the presence of reprioritization, whereas the estimation of true change was very similar to the previous one: 3.87. CONCLUSIONS: RS and true change in HRQoL can be evaluated in the presence of formative indicators. Defining a measurement model by formative or reflective indicators can lead to different results.

Viability of a MSQOL-54 general health-related quality of life score using bifactor model.

BACKGROUND: MSQOL-54 is a multidimensional, widely-used, health-related quality of life (HRQOL) instrument specific for multiple sclerosis (MS). Findings from the validation study suggested that the two MSQOL-54 composite scores are correlated. Given this correlation, it could be assumed that a unique total score of HRQOL may be calculated, with the advantage to provide key stakeholders with a single overall HRQOL score. We aimed to assess how well the bifactor model could account for the MSQOL-54 structure, in order to verify whether a total HRQOL score can be calculated. METHODS: A large international database (3669 MS patients) was used. By means of confirmatory factor analysis, we estimated a bifactor model in which every item loads onto both a general factor and a group factor. Fit of the bifactor model was compared to that of single and two second-order factor models by means of Akaike information and Bayesian information criteria reduction. Reliability of the total and subscale scores was evaluated with Mc Donald's coefficients (omega, and omega hierarchical). RESULTS: The bifactor model outperformed the two second-order factor models in all the statistics. All items loaded satisfactorily (≥ 0.40) on the general HRQOL factor, except the sexual function items. Omega coefficients for total score were very satisfactory (0.98 and 0.87). Omega hierarchical for subscales ranged between 0.22 to 0.57, except for the sexual function (0.70). CONCLUSIONS: The bifactor model is particularly useful when it is intended to acknowledge multidimensionality and at the same time take account of a single general construct, as the HRQOL related to MS. The total raw score can be used as an estimate of the general HRQOL latent score.

Is HDL cholesterol protective in patients with type 2 diabetes? A retrospective population-based cohort study.

BACKGROUND: The protective role of high HDL cholesterol levels against cardiovascular diseases has been recently questioned. Limited data are available on this specific topic in patients with type 2 diabetes mellitus (T2DM). We aimed to evaluate the association of HDL cholesterol concentrations with all-cause and cause-specific mortality in a historical cohort of T2DM patients with 14 years of follow-up. METHODS: This is a retrospective population-based cohort study involving 2113 T2DM patients attending the Diabetic Clinic of Asti. Survival analyses were performed to assess hazard ratios for overall and specific-cause mortality by HDL cholesterol tertiles, using the middle HDL cholesterol tertile as a reference. RESULTS: The mean age was 66 ± 11 years; 51.4% of patients had low HDL-cholesterol levels. After a 14-year follow-up, 973/2112 patients had died (46.1%). The HDL cholesterol tertile cut-off points were 37.5 and 47.5 mg/dL (males) and 41.5 and 52.0 mg/dL (females). No associations between lower and upper HDL cholesterol tertiles respectively and all-cause (HR = 1.12; 95% CI 0.96-1.32; HR = 1.11; 0.95-1.30), cardiovascular (HR = 0.97; 0.77-1.23; HR = 0.94; 0.75-1.18) or cancer (HR = 0.92; 0.67-1.25; HR = 0.89; 0.66-1.21) mortality were found. A significantly increased risk for infectious disease death was found both in the lower (HR = 2.62; 1.44-4.74) and the upper HDL-cholesterol tertiles (HR = 2.05; 1.09-3.85) when compared to the reference. Individuals in the upper tertile showed an increased risk for mortality due to diabetes-related causes (HR = 1.87; 1.10-3.15). CONCLUSIONS: Our results corroborate the hypothesis that HDL cholesterol levels are nonprotective in T2DM patients. The U-shaped association between HDL-cholesterol levels and mortality associated with infectious diseases should be verified by further studies.

Acute assessment of subjective appetite and implicated hormones after a hypnosis-induced hallucinated meal: a randomized cross-over pilot trial.

The use of hypnosis can generate hallucinatory phenomena, which ranged from vivid/auditory imagery to fully developed "hallucinations" in selected people. The aim of this pilot trial was investigating the acute effects of a hypnosis-induced hallucinated breakfast (HB) compared to those of a real breakfast (RB) on subjective appetite and appetite-regulating hormones in highly hypnotizable individuals. Eight healthy post-menopausal women were recruited to consume two meals: the HB and the RB in a randomized crossover design. Participants underwent appetite sensations measurements (before meal and each 30-min until 270-min) and blood sample collection (at 0, 20, 60, 90, 180-min). A 3-day food-record was filled after each meal. The adjusted repeated measures ANCOVA did not show any meal×time interactions on subjective appetite postprandially. As expected, significantly higher glucose (p < 0.001), insulin (p < 0.001), and lower free fatty acid (p < 0.001) concentrations were found after the RB, but not following HB. Furthermore, RB significantly increased postprandial levels of glucagon-like-peptide-1 and peptide-YY at 20, 60, 90 and 180-min, whereas acylated-ghrelin and leptin levels did not differ. Postprandial neuropeptide-Y and orexin-A values significantly increased at different time-points after RB, but not following HB, while α-melanocyte-stimulating hormone levels enhanced after HB only. Energy intakes were significantly lower after HB on the test-day only (HB = 1146.6 ± 343.8 vs RB = 1634.7 ± 274.2 kcal/d; p = 0.003). Appetite sensation might be modulated by fully developed meal "hallucination" induced by hypnosis, likely affecting brain-peptides implicated in the appetite regulation. However, further studies are needed to verify these results obtained in a highly selected group of individuals. NCT03934580.

Assessing measurement invariance of MSQOL-54 across Italian and English versions.

PURPOSE: The Multiple Sclerosis Quality of Life-54 (MSQOL-54) is a specific multiple sclerosis (MS) health-related quality of life inventory consisting of 52 items organized into 12 subscales plus two single items. No study was found in literature assessing its measurement invariance across language versions. We investigated whether MSQOL-54 items provide unbiased measurements of underlying constructs across Italian and English versions. METHODS: Three constrained levels of measurement invariance were evaluated: configural invariance where equivalent numbers of factors/factor patterns were required; metric invariance where equivalent factor loadings were required; and scalar invariance where equivalent item intercepts between groups were required. Comparative fit index (CFI), root mean square error of approximation (RMSEA), and standardized root mean square residual (SRMR) fit indices and their changes between nested models were used to assess tenability of invariance constraints. RESULTS: Overall, the dataset included 3669 MS patients: 1605 (44%) Italian, mean age 41 years, 62% women, 69% with mild level of disability; 2064 (56%) English-speaking (840 [41%] from North America, 797 [39%] from Australasia, 427 [20%] from UK and Ireland), mean age 46 years, 83% women, 54% with mild level of disability. The configural invariance model showed acceptable fit (RMSEA = 0.052, CFI = 0.904, SRMR = 0.046); imposing loadings and intercepts equality constraints produced negligible worsening of fit (ΔRMSEA < 0.001, ΔCFI = - 0.002, ΔSRMR = 0.002 for metric invariance; ΔRMSEA = 0.003, ΔCFI = - 0.013, ΔSRMR = 0.003 for scalar invariance). CONCLUSIONS: These findings support measurement invariance of the MSQOL-54 across the two language versions, suggesting that the questionnaire has the same meaning and the same measurement paramaters in the Italian and English versions.

Italian translation and psychometric validation of the Manual Ability Measure-36 (MAM-36) and its correlation with an objective measure of upper limb function in patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system with an unpredictable course. During its course, deficits affecting upper limb functions may occur. Hence, there is a need for self-administered scales providing a comprehensive assessment of upper limb functions. The Manual Ability Measure-36 (MAM-36), which investigates patients' performance in activities of daily living requiring upper limb function, has not been adapted and validated in the Italian context. OBJECTIVES: We develop an Italian translation and validation of the MAM-36 in a population of people with MS (PwMS), explore its psychometric properties and investigate its associations with clinical data and the Nine Hole Peg Test (9-HPT). RESEARCH PLAN AND METHODS: The multicentre study involved five Italian neurological centres. Subjects were evaluated using EDSS, 9-HPT and the MAM-36 scale. We used confirmatory factor analysis and Rasch analysis to investigate the properties of the MAM-36. RESULTS: We enrolled 218 PwMS. Results supported the unidimensionality of the MAM-36, and adequate functioning of rating scale and items. Additionally, the MAM-36 showed weak negative associations with age and disease duration, and moderate associations with EDSS and 9-HPT scores. DISCUSSION: The adapted MAM-36 showed adequate psychometric properties. However, indications of problematic targeting to PwMS with low disability emerged. For this reason, use of the scale appears to be more suitable among patients with moderate-to-severe disability.

Reliability and acceptability of the Multiple Sclerosis Quality of Life-29 questionnaire in an English-speaking cohort.

BACKGROUND: Multiple Sclerosis Quality-of-Life Questionnaire-54 (MSQoL-54) is a disease-specific instrument for assessing health-related quality of life (HRQoL). Due to the number of items, the time taken to complete it is long. A shorter 29-item version, Multiple Sclerosis Quality-of-Life Questionnaire-29 (MSQoL-29) is yet to be evaluated in English. OBJECTIVE: To assess reliability and acceptability of English version of MSQoL-29. METHODS: Among 100 participants with MS who first completed both MSQoL-54 and MSQoL-29, 91 completed MSQoL-29 after 4-8 weeks. We looked for internal consistency (Cronbach's alpha), acceptability, reliability (intraclass correlation coefficients (ICCs)) and agreement (Bland-Altman plots). RESULTS: ICCs were strongly positive between MSQoL-54 and MSQoL-29 (Physical Health Composite (PHC) -ICC = 0.914, confidence interval (CI) = 0.872-0.942; Mental Health Composite (MHC) - ICC = 0.875, CI = 0.814-0.916) and between the two MSQoL-29 (PHC - ICC = 0.970, CI = 0.955-0.980; MHC - ICC = 0.937, CI = 0.904-0.958). On Bland-Altman plots, the MSQoL-29 scores of 95% of participants during two visits were within the limits of agreement (LOAs). Time taken to complete MSQoL-29 was 7.2 ± 2.9 minutes and MSQoL-54 was 19.79 ± 5.4 minutes (p = 0.0001). CONCLUSION: MSQoL-29 has good test-retest reliability in English-speaking population and was quicker to complete.

eMSQOL-29: Prospective validation of the abbreviated, electronic version of MSQOL-54.

BACKGROUND: We recently devised a shortened version of the 54-item Multiple Sclerosis Quality of Life (MSQOL-54) in paper (MSQOL-29, consisting of 25 items forming 7 subscales and 4 single items, and one filter question for 3 'sexual function' items) and electronic format (eMSQOL-29). OBJECTIVES: To prospectively assess eMSQOL-29 psychometric properties, acceptability/equivalence versus MSQOL-29. METHODS: Multiple sclerosis (MS) patients ( n = 623; Expanded Disability Status Scale (EDSS) range 0.0-9.0) completed eMSQOL-29, Hospital Anxiety and Depression Scale, Functional Assessment of MS (FAMS), European Quality of life Five Dimensions-3L, and received EDSS and Symbol Digit Modalities Test (SDMT). Equivalence versus MSQOL-29 was assessed in 242 patients (randomized cross-over design). RESULTS: 'Sexual function' items were filtered out by 273 patients (47%). No multi-item scale had floor effect, while five had ceiling effect. Cronbach's alpha range was 0.88-0.90. Confirmatory factor analysis showed good overall fit and the two-factor solution for composite scores was confirmed. Criterion validity was sub-optimal for 'cognitive function' (vs SDMT, r = 0.25) and 'social function' (vs FAMS social function, r = 0.38). eMSQOL-29 equivalence was confirmed and its acceptability was good. CONCLUSION: eMSQOL-29 showed good internal consistency, factor structure and no floor effect, while most subscales had some ceiling effect. Criterion validity was sub-optimal for two subscales. Equivalence and acceptability were good.

Randomized controlled trial of a home-based palliative approach for people with severe multiple sclerosis.

BACKGROUND: Evidence on the efficacy of palliative care in persons with severe multiple sclerosis (MS) is scarce. OBJECTIVE: To assess the efficacy of a home-based palliative approach (HPA) for adults with severe MS and their carers. METHODS: Adults with severe MS-carer dyads were assigned (2:1 ratio) to either HPA or usual care (UC). At each center, a multi-professional team delivered the 6-month intervention. A blind examiner assessed dyads at baseline, 3 months, and 6 months. Primary outcome measures were Palliative care Outcome Scale-Symptoms-MS (POS-S-MS) and Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW, not assessed in severely cognitively compromised patients). RESULTS: Of 78 dyads randomized, 76 (50 HPA, 26 UC) were analyzed. Symptom burden (POS-S-MS) significantly reduced in HPA group compared to UC ( p = 0.047). Effect size was 0.20 at 3 months and 0.32 at 6 months, and statistical significance was borderline in per-protocol analysis ( p = 0.062). Changes in SEIQoL-DW index did not differ in the two groups, as changes in secondary patient and carer outcomes. CONCLUSION: HPA slightly reduced symptoms burden. We found no evidence of HPA efficacy on patient quality of life and on secondary outcomes.

Neuropsychological correlates of instrumental activities of daily living in neurocognitive disorders: a possible role for executive dysfunction and mood changes.

ABSTRACTSince baseline executive dysfunction predicts worsening Instrumental Activities of Daily Living (i-ADL) over time and progression to Alzheimer's Disease (AD), we aimed to analyze the role of neuropsychological variables to outline which factors can contribute to functional impairment. Specific attention to executive functions (EFs) has been given.A total of 144 subjects complaining of different cognitive deficits - ranging from "MCI likely due to AD" to "mild AD patients" - underwent an overall neuropsychological assessment. The Behavioral Assessment of the Dysexecutive Syndrome was used to analyze EFs. We conducted multiple linear regression analyses to study whether the level of independent living skills - assessed with the Lawton-scale - could be associated with cognitive and behavioral measurements.We found a significant association between i-ADL and specific EFs measured by Rule Shift Cards (p = 0.04) and Modified Six Elements (p = 0.02). Moreover, considering i-ADL scores, we observed an involvement of mood changes and a reduced awareness of deficits in terms of Hamilton Depression Rating Scale (p = 0.02) and Awareness of Deficit Questionnaire - Dementia scale (p < 0.0001), respectively.Our results suggest the importance of considering the association between a reduction in i-ADL and executive dysfunction in patients who have AD etiopathology, for which the ability to inhibit a response, self-monitoring, set-shifting and mood deflection play a key role. Besides, no straightforward associations between i-ADL scores and global cognition, memory, language comprehension, attention, and perspective taking abilities were found.

Multivariate projection method to investigate inflammation associated with secondary insults and outcome after human traumatic brain injury: a pilot study.

BACKGROUND: Neuroinflammation has been proposed as a possible mechanism of brain damage after traumatic brain injury (TBI), but no consensus has been reached on the most relevant molecules. Furthermore, secondary insults occurring after TBI contribute to worsen neurological outcome in addition to the primary injury. We hypothesized that after TBI, a specific pattern of cytokines is related to secondary insults and outcome. METHODS: A prospective observational clinical study was performed. Secondary insults by computerized multimodality monitoring system and systemic value of different cytokines were collected and analysed in the first week after intensive care unit admission. Neurological outcome was assessed at 6 months (GOSe). Multivariate projection technique was applied to analyse major sources of variation and collinearity within the cytokines dataset without a priori selecting potential relevant molecules. RESULTS: Twenty-nine severe traumatic brain injury patients undergoing intracranial pressure monitoring were studied. In this pilot study, we demonstrated that after TBI, patients who suffered of prolonged and severe secondary brain damage are characterised by a specific pattern of cytokines. Patients evolving to brain death exhibited higher levels of inflammatory mediators compared to both patients with favorable and unfavorable neurological outcome at 6 months. Raised ICP and low cerebral perfusion pressure occurred in 21 % of good monitoring time. Furthermore, the principal components selected by multivariate projection technique were powerful predictors of neurological outcome. CONCLUSIONS: The multivariate projection method represents a valuable methodology to study neuroinflammation pattern occurring after secondary brain damage in severe TBI patients, overcoming multiple putative interactions between mediators and avoiding any subjective selection of relevant molecules.

Quality of life and patient preferences: identification of subgroups of multiple sclerosis patients.

PURPOSE: The aim of this study was to estimate preferences related to quality of life attributes in people with multiple sclerosis, by keeping heterogeneity of patient preference in mind, using the latent class approach. METHODS: A discrete choice experiment survey was developed using the following attributes: activities of daily living, instrumental activities of daily living, pain/fatigue, anxiety/depression and attention/concentration. Choice sets were presented as pairs of hypothetical health status, based upon a fractional factorial design. RESULTS: The latent class logit model estimated on 152 patients identified three subpopulations, which, respectively, attached more importance to: (1) the physical dimension; (2) pain/fatigue and anxiety/depression; and (3) instrumental activities of daily living impairments, anxiety/depression and attention/concentration. A posterior analysis suggests that the latent class membership may be related to an individual's age to some extent, or to diagnosis and treatment, while apart from energy dimension, no significant difference exists between latent groups, with regard to Multiple Sclerosis Quality of Life-54 scales. CONCLUSIONS: A quality of life preference-based utility measure for people with multiple sclerosis was developed. These utility values allow identification of a hierarchic priority among different aspects of quality of life and may allow physicians to develop a care programme tailored to patient needs.

Self-unawareness of levodopa induced dyskinesias in patients with Parkinson's disease.

The study analyzes the presence of dyskinesias-reduced-self-awareness in forty-eight patients suffering from Parkinson's disease (PD). As the association with executive dysfunction is a matter of debate and we hypothesize it plays an important role in dyskinesias self-unawareness, we analyzed the role of dopaminergic treatment on the medial-prefrontal-ventral-striatal circuitry using a neurocognitive approach. Special attention was given to metacognitive abilities related to action-monitoring that represent a novel explanation of the phenomenon. PD patients were assessed using different rating scales that we devised to measure movement awareness disorders. In order to ascertain whether each variable measured at a cognitive-clinical level contributes to predicting the scores of the movement-disorder-awareness-scales, we conducted multiple logistic regression models using the latter as binary dependent variables. We used the Wisconsin Card Sorting Test-metacognitive-version to assess the executive functions of the prefrontal-ventral-striatal circuitry. Data showed that a reduction of self-awareness using the Dyskinesia rating scale was associated with global monitoring (p=.04), monitoring resolution (p=.04) and control sensitivity (p=.04). Patients failed to perceive their performance, distinguish between correct and incorrect sorts, be confident in their choice and consequently decide to gamble during the task. We did not find any association with executive functions using the hypo-bradykinesia rating scale. Our findings indicate that when the comparator mechanism for monitoring attentive performance is compromised at a prefrontal striatal level, patients lose the ability to recognize their motor disturbances that do not achieve conscious awareness.

Levofloxacin Prophylaxis Versus no Prophylaxis in Acute Myeloid Leukemia During Post-Induction Aplasia: a Single Center Study.

Background: Acute myeloid leukemia (AML) patients are at high risk of infections during post-induction neutropenia. Recently, the role of antibacterial prophylaxis has been reconsidered due to concerns about the emergence of multi-resistant pathogens. The aim of the present study was to evaluate the impact of avoiding prophylaxis on the rate of induction death (primary endpoint), neutropenic fevers, bloodstream infections (BSIs), resistant pathogens BSIs and septic shocks (secondary endpoints). Methods: We performed a retrospective single-center study including 373 AML patients treated with intensive induction chemotherapy, divided into two groups according to levofloxacin prophylaxis given (group A, gA) or not (group B, gB). Results: Neutropenic fever was observed in 91% of patients in gA and 97% in gB (OR 0.35, IC95% 0.08 - 1.52, p=0162). The rate of BSIs was 27% in gA compared to 34% in gB (OR 0.69, 0.38 - 1.25, p=0.222). The induction death rate was 5% in gA and 3% in gB (OR 1.50, 0.34 - 6.70, p=0.284). Fluoroquinolones (FQ) resistant pathogens were responsible for 59% of total BSIs in gA and 22% in gB (OR 5.07, 1.87 - 13.73, p=0.001); gram-negative BSIs due to multi-drug resistant organisms were 31% in gA and 36% in gB (OR 0.75, 0.15 - 3.70, p=0.727). Conclusions: Despite its limitations (retrospective nature, single-center, different cohort size), the present study showed that avoiding levofloxacin prophylaxis was not associated with an increased risk of induction death. The cumulative incidence of neutropenic fever was higher in non-prophylaxis group, while no difference was observed for BSIs. In the prophylaxis group we observed a higher incidence of FQ-resistant organisms.