Decision analysis of allogeneic hematopoietic stem cell transplantation for patients with myelodysplastic syndrome stratified according to the revised International Prognostic Scoring System.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) represents the only curative treatment for patients with myelodysplastic syndrome (MDS), but involves non-negligible morbidity and mortality. Crucial questions in clinical decision-making include the definition of optimal timing of the procedure and the benefit of cytoreduction before transplant in high-risk patients. We carried out a decision analysis on 1728 MDS who received supportive care, transplantation or hypomethylating agents (HMAs). Risk assessment was based on the revised International Prognostic Scoring System (IPSS-R). We used a continuous-time multistate Markov model to describe the natural history of disease and evaluate the effect of different treatment policies on survival. Life expectancy increased when transplantation was delayed from the initial stages to intermediate IPSS-R risk (gain-of-life expectancy 5.3, 4.7 and 2.8 years for patients aged ⩽55, 60 and 65 years, respectively), and then decreased for higher risks. Modeling decision analysis on IPSS-R versus original IPSS changed transplantation policy in 29% of patients, resulting in a 2-year gain in life expectancy. In advanced stages, HMAs given before transplant is associated with a 2-year gain-of-life expectancy, especially in older patients. These results provide a preliminary evidence to maximize the effectiveness of allo-SCT in MDS.

Minimal morphological criteria for defining bone marrow dysplasia: a basis for clinical implementation of WHO classification of myelodysplastic syndromes.

The World Health Organization classification of myelodysplastic syndromes (MDS) is based on morphological evaluation of marrow dysplasia. We performed a systematic review of cytological and histological data from 1150 patients with peripheral blood cytopenia. We analyzed the frequency and discriminant power of single morphological abnormalities. A score to define minimal morphological criteria associated to the presence of marrow dysplasia was developed. This score showed high sensitivity/specificity (>90%), acceptable reproducibility and was independently validated. The severity of granulocytic and megakaryocytic dysplasia significantly affected survival. A close association was found between ring sideroblasts and SF3B1 mutations, and between severe granulocytic dysplasia and mutation of ASXL1, RUNX1, TP53 and SRSF2 genes. In myeloid neoplasms with fibrosis, multilineage dysplasia, hypolobulated/multinucleated megakaryocytes and increased CD34+ progenitors in the absence of JAK2, MPL and CALR gene mutations were significantly associated with a myelodysplastic phenotype. In myeloid disorders with marrow hypoplasia, granulocytic and/or megakaryocytic dysplasia, increased CD34+ progenitors and chromosomal abnormalities are consistent with a diagnosis of MDS. The proposed morphological score may be useful to evaluate the presence of dysplasia in cases without a clearly objective myelodysplastic phenotype. The integration of cytological and histological parameters improves the identification of MDS cases among myeloid disorders with fibrosis and hypocellularity.

Music, music therapy and dementia: a review of literature and the recommendations of the Italian Psychogeriatric Association.

This study reviews the most recent (from 2000 to 2011) Clinical Controlled Trials (CCT) and Randomized Controlled Trials (RCT) concerning the use of music and music-therapy (MT) in the context of dementia and related issues. Studies which explored the efficacy of music and MT on behavioral and psychological symptoms of dementia (BPSD) are prevalent, while those aiming at assessing a potential effect of these approaches on cognitive and physiological aspects are scant. Although with some limitations, the results of these studies are consistent with the efficacy of MT approach on BPSD. In this context, the ability of the music therapist to directly interact with the patients appears to be crucial for the success of the intervention. This review was endorsed by the Italian Psychogeriatric Association (AIP) and represents its view about the criteria to select appropriate music and MT approaches in the field of dementia. Accordingly, we have developed a list of recommendations to facilitate the current use of these techniques in the context of non-pharmacological treatments for patients with dementia.

Addendum to 'Efficacy of music therapy treatment based on cycles of sessions: a randomised controlled trial' (Raglio et al., 2010).

OBJECTIVES: The aim of this paper is to provide further detail about the results of a randomised controlled study published in this journal (Raglio et al., 2010, 14, 900-904), in which we assessed the efficacy of music therapy (MT) on the behavioural disturbances in people with moderate-severe dementia. METHODS: Sixty patients were randomly assigned to the experimental (MT and standard care) and control group (standard care only). The experimental group received three cycles of 12 MT sessions each, three times a week. Each cycle of treatment was followed by one month of washout period, while the standard care activities continued over time. RESULTS: The impact of the treatment (12 MT sessions) was reliable on NPI global scores, as the interaction Time by Group was significant (F(1,49) = 4.09, p = 0.049). After the end of the treatment the NPI global scores of the experimental and control groups tended to become similar, as both groups worsened (Time effect: F(1,48) = 4.67, p = 0.014) and the difference between them disappeared (F < 1). Interaction Time by Group was not significant. CONCLUSIONS: The study confirms that active MT determines a positive response and can amplify and strengthen the efficacy of therapeutic interventions towards people with dementia.

Efficacy of music therapy treatment based on cycles of sessions: a randomised controlled trial.

We undertook a randomised controlled trial to assess whether a music therapy (MT) scheme of administration, including three working cycles of one month spaced out by one month of no treatment, is effective to reduce behavioural disturbances in severely demented patients. Sixty persons with severe dementia (30 in the experimental and 30 in the control group) were enrolled. Baseline multidimensional assessment included demographics, Mini Mental State Examination (MMSE), Barthel Index and Neuropsychiatry Inventory (NPI) for all patients. All the patients of the experimental and control groups received standard care (educational and entertainment activities). In addition, the experimental group received three cycles of 12 active MT sessions each, three times a week. Each 30-min session included a group of three patients. Every cycle of treatment was followed by one month of wash-out. At the end of this study, MT treatment resulted to be more effective than standard care to reduce behavioural disorders. We observed a significant reduction over time in the NPI global scores in both groups (F(7,357) = 9.06, p < 0.001) and a significant difference between groups (F(1,51) = 4.84, p < 0.05) due to a higher reduction of behavioural disturbances in the experimental group at the end of the treatment (Cohen's d = 0.63). The analysis of single NPI items shows that delusions, agitation and apathy significantly improved in the experimental, but not in the control group. This study suggests the effectiveness of MT approach with working cycles in reducing behavioural disorders of severely demented patients.

Temporal lobe asymmetry in patients with Alzheimer's disease with delusions.

OBJECTIVE: To test the hypothesis that delusions are associated with asymmetric involvement of the temporal lobe regions in Alzheimer's disease. METHODS: Temporal lobe atrophy was assessed with a linear measure of width of the temporal horn (WTH) taken from CT films. Temporal asymmetry was computed as the right/left (R/L) ratio of the WTH in 22 non-delusional and 19 delusional patients with Alzheimer's disease. Delusional patients had paranoid delusions (of theft, jealousy, persecution). None of the patients had misidentifications or other delusions of non-paranoid content. RESULTS: The R/L ratio indicated symmetric temporal horn size in the non-delusional (mean 1. 05 (SD 0.20), and right greater than left temporal horn in the delusional patients (mean 1.30, (SD 0.46); t=2.27, df=39, p=0.03). When patients were stratified into three groups according to the R/L ratio, 47% of the delusional (9/19) and 14% of the non-delusional patients (3/21; chi(2)=5.6, df=1, p=0.02) showed right markedly greater than left WTH. CONCLUSIONS: Predominantly right involvement of the medial temporal lobe might be a determinant of paranoid delusions in the mild stages of Alzheimer's disease.

The milan overall dementia assessment and the mini-mental state examination compared: an epidemiological investigation of dementia.

We assessed the validity of two screening tests [the Mini-Mental State Examination (MMSE) and the Milan Overall Dementia Assessment or (MODA)] in a population study on the prevalence of Alzheimer's disease, carried out in a small town in the north of Italy. A random sample of 1000 subjects aged 60 years or over entered the study. Subjects who scored below the cut-off points on MODA or on MMSE, or both, were further investigated with neuropsychological, laboratory and instrumental tests to ascertain a final diagnosis, which was considered as the gold standard. Our findings show that MODA has a higher sensitivity than MMSE in detecting subjects affected by dementing illnesses, while MMSE shows a higher specificity. MODA seems to be preferable to MMSE as a screening test for studies where a very high sensitivity is required.

Comparison of two scoring systems of the Mini-Mental State Examination as a screening test for dementia.

The difference in validity in detecting dementia of two different scoring systems (age- and education-adjusted versus raw scores) of the Mini-Mental State Examination (MMSE), was assessed in an epidemiological study on the prevalence of dementia. A second, independent, psychometric screening tool, the Milan Overall Dementia Assessment (MODA), was also used. A group of 829 subjects over age 59 took part in the study. Subjects scoring below the cut-off point of the MMSE and/or MODA were clinically evaluated. Clinical diagnoses were adopted as the gold standard. Sensitivity, specificity, positive, and negative predictive values of the two tests were calculated. Our findings show that the correction for age and education of the raw score of the MMSE causes the loss of the mildest demented patients and heavily reduces the sensitivity of the screening test (from 85.7% to 71.4%), while it accounts for a moderate improvement in the specificity (from 90.0% to 96.3%). A possible explanation for this seeming paradox is proposed.