A New Potential Resource in the Fight against Candida auris: the Cinnamomum zeylanicum Essential Oil in Synergy with Antifungal Drug.

Candida auris is a multidrug-resistant fungus known to be a global public health problem. The skin-based transmission, together with the marked resistance to drugs, resulted in its rapid spread to all continents. The aim of this study was to identify an essential oil (EO) active in the fight against C. auris. A total of 15 EOs were tested against 10 clinical strains of C. auris. Cinnamomum zeylanicum EO (CZ-EO) was the most effective (MIC90 and MFC90 equal to 0.06% vol/vol). Three fractions obtained from CZ-EO, and the cinnamaldehyde (CIN), the major chemical compound, were tested to identify the principal compound effectives against C. auris. All CIN-containing samples showed anti-fungal activity. To study the synergy with fluconazole, CZ-EO, its active fraction (FR2), and CIN were tested in checkerboard tests. Results show that CZ-EO and FR2, but not CIN, synergize with fluconazole. Furthermore, only the copresence of CZ-EO or FR2 synergize with fluconazole at therapeutic concentrations of the drug (0.45 ± 0.32 µg/mL and 0.64 ± 0.67 µg/mL, respectively), while CIN only shows additive activity. In vivo studies conducted on Galleria mellonella larvae show the absence of toxicity of CZ-EO up to concentrations of 16% vol/vol, and the ability of CZ-EO to reactivate the efficacy of fluconazole when formulated at synergic concentrations. Finally, biochemical tests were made to study the mechanism of action of CZ-EO. These studies show that in the presence of both fluconazole and CZ-EO, the activity of fungal ATPases decreases and, at the same time, the amount of intracellular drug increases. IMPORTANCE This study highlights how small doses of CZ-EO are able to inhibit the secretion of fluconazole and promote its accumulation in the fungal cell. In this manner, the drug is able to exert its pharmacological effects bypassing the resistance of the yeast. If further studies will confirm this synergy, it will be possible to develop new therapeutic formulations active in the fight against C. auris resistances.

Box and block test, hand grip strength and nine-hole peg test: correlations between three upper limb objective measures in multiple sclerosis.

BACKGROUND AND PURPOSE: Limited data are available in the literature for upper limb impairment in multiple sclerosis (MS). This study aimed to report the distribution of values of hand grip strength (HGS), of the box and block test (BBT) and of the nine-hole peg test (9HPT) correlated with demographic and clinical data in subjects with MS. METHODS: This study involved five Italian neurological centres. The inclusion criteria were age ≥ 18, MS diagnosis, stable disease phase, right-hand dominance. All subjects underwent HGS, BBT and 9-HPT evaluation. RESULTS: In all, 202 subjects with MS were enrolled: 137 females; mean age 48.4 years; mean Expanded Disability Status Scale (EDSS) 4.17; mean disease duration 14.12 years; disease course 129 relapsing-remitting, 21 primary progressive and 52 secondary progressive MS subjects; mean right HGS 25.3 kg, left 23.2 kg; mean right BBT 45.7 blocks, left 44.9 blocks; mean right 9-HPT 30.7 s, left 33.4 s. All results were statistically significantly different compared to healthy controls. HGS, BBT and 9-HPT were associated with age, EDSS and disease duration, whilst disease course correlated with BBT and 9-HPT. The BBT and 9-HPT scores significantly differed according to level of disability (EDSS ≤3.0, 3.5-5.5, ≥6.0). CONCLUSION: Hand grip strength and BBT value distribution in a large MS population is reported. Correlations between HGS, BBT and 9-HPT were generally low.

Examining the validity of the multiple-sclerosis walking scale-12 with Rasch analysis: Results from an Italian study.

BACKGROUND: The Multiple Sclerosis Walking Scale (MSWS-12) has showed good psychometric properties in reports exploring its validity using Classical Test Theory methods. Findings from recent studies using Item Response Theory methods advance the idea that some aspects of the MSWS-12 does not fully comply with some requirements of sound measurement. RESEARCH QUESTION: The present study investigated whether the measurement properties of the Italian version of the MSWS-12 met the assumptions of the Rasch model. METHODS: Sample consisted of 199 patients with a diagnosis of MS (50% female; Mean age (SD) = 48.15 (12.33)). Analyses were performed using both unidimensional and multidimensional Rasch modeling techniques. RESULTS: Rating scale for items assessing need for support when walking, and ability to run, showed significant functioning problems. A revision of the rating scale improved the measurement properties of these items. Items assessing need for support showed signs of multidimensionality and differential item functioning when controlling for patients' disease course and EDSS score. Additionally, included items did not appear to cover the full range of impairment as observed in the sample. SIGNIFICANCE: Emerging findings are consistent with those from previous studies in highlighting the need for a revision of the current content of the MSWS-12, and the inclusion of new items assessing impairment at the lower end of the disability continuum.

Impaired taste sensation in type 2 diabetic patients without chronic complications: a case-control study.

PURPOSE: Few and contradictory data suggest changes in taste perception in type 2 diabetes (T2DM), potentially altering food choices. We, therefore, analyzed taste recognition thresholds in T2DM patients with good metabolic control and free of conditions potentially impacting on taste, compared with age-, body mass index-, and sex-matched normoglycemic controls. METHODS: An ascending-concentration method was used, employing sucrose (sweet), sodium chloride (salty), citric acid (sour), and quinine hydrochloride (bitter), diluted in increasing concentration solutions. The recognition threshold was the lowest concentration of correct taste identification. RESULTS: The recognition thresholds for the four tastes were higher in T2DM patients. In a multiple regression model, T2DM [ß = 0.95; 95% CI 0.32-1.58; p = 0.004 (salty); ß = 0.61; 0.19-1.03; p = 0.006 (sweet); ß = 0.78; 0.15-1.40; p = 0.016 (sour); ß = 0.74; 0.22-1.25; p = 0.006 (bitter)] and waist circumference [ß = 0.05; 0.01-0.08; p = 0.012 (salty); ß = 0.03; 0.01-0.05; p = 0.020 (sweet); ß = 0.04; 0.01-0.08; p = 0.020 (sour); ß = 0.04; 0.01-0.07; p = 0.007 (bitter)] were associated with the recognition thresholds. Age was associated with salty (ß = 0.06; 0.01-0.12; p = 0.027) and BMI with sweet thresholds (ß = 0.06; 0.01-0.11; p = 0.019). CONCLUSIONS: Taste recognition thresholds were higher in uncomplicated T2DM, and central obesity was significantly associated with this impairment. Hypogeusia may be an early sign of diabetic neuropathy and be implicated in the poor compliance of these patients to dietary recommendations.

Self-reported adherence to diet and preferences towards type of meal plan in patient with type 2 diabetes mellitus. A cross-sectional study.

BACKGROUND AND AIMS: Few studies have evaluated the attitudes of patients with type 2 diabetes mellitus (T2DM) towards the given dietary plans. In this study, we aimed to evaluate: i) the self-reported adherence of T2DM patients to the prescribed diets; ii) the use of other types of diet schemes; iii) the patients' preferences towards the type of meal plans. METHODS AND RESULTS: A 16 multiple-choice items questionnaire was administered to 500 T2DM patients; 71.2% (356/500) of them had the perception of having received a dietary plan; only 163/356 declared to be fully adherent. The latter had lower BMI (25.8 ± 4.5 vs 29.1 ± 4.5 kg/m2, p < 0.001) than patients who were partly adherent. Among patients not following the given diet, 61.8% was eating in accordance to a self-made diet and 20.9% did not follow any diet. Only a few patients (2.4%) had tried a popular diet/commercial program. Most patients preferred either a "sufficiently free" (201/500) or a "free" (218/500) scheme. The use of supplements attracted younger, obese individuals, with higher education, and most managers. In a multinomial regression model, age and diabetes duration were inversely associated with the choice of a "rigid" scheme, diabetes duration and glycated hemoglobin levels were inversely correlated with a "free" diet choice, obesity was associated with a "strategic" scheme choice, while lower education (inversely) and obesity (directly) correlated with the preference for "supplement use". CONCLUSIONS: Socio-cultural/individual factors could affect attitudes and preferences of T2DM patients towards diet. These factors should be considered in order to draw an individually tailored dietary plan.

Quality of life and hormones after sex reassignment surgery.

BACKGROUND: Transpeople often look for sex reassignment surgery (SRS) to improve their quality of life (QoL). The hormonal therapy has many positive effects before and after SRS. There are no studies about correlation between hormonal status and QoL after SRS. AIM: To gather information on QoL, quality of sexual life and body image in transpeople at least 2 years after SRS,to compare these results with a control group and to evaluate the relations between the chosen items and hormonal status. SUBJECTS AND METHODS: Data from 60 transsexuals and from 60 healthy matched controls were collected. Testosterone,estradiol, LH and World Health Organization Quality of Life (WHOQOL-100) self-reported questionnaire were evaluated. Student's t test was applied to compare transsexuals and controls. Multiple regression model was applied to evaluate WHOQOL's chosen items and LH. RESULTS: The QoL and the quality of body image scores intranspeople were not statistically different from the matched control groups' ones. In the sexual life subscale,transwomen's scores were similar to biological women's ones, whereas transmen's scores were statistically lower than biological men's ones (P = 0.003). The quality of sexual life scored statistically lower in transmen than intranswomen (P = 0.048). A significant inverse relationship between LH and body image and between LH and quality of sexual life was found. CONCLUSIONS: This study highlights general satisfaction after SRS. In particular, transpeople's QoL turns out to be similar to Italian matched controls. LH resulted inversely correlated to body image and sexual life scores.

Alberta Breakthrough Pain Assessment Tool: A validation multicentre study in cancer patients with breakthrough pain.

BACKGROUND: Cancer-related breakthrough pain (BTP) is a common and quite challenging pain syndrome, with significant impact on quality of life. To date, no widely recognized and validated tool for the diagnosis and evaluation of BTP exists. The Alberta Breakthrough Pain Assessment Tool (ABPAT) underwent a validation process during its development, but no experience of its implementation in clinical practice has been reported. METHODS: ABPAT was tested in a cohort of cancer patients suffering from chronic severe cancer-related pain in order to assess its acceptability and efficacy as a tool for the characterization of BTP. RESULTS: A total of consecutive 249 patients from seven different centres were included in a 2-month study period and all completed the questionnaire; 231 out of the 249 (92.8%) stated that questions were easily understandable and 217 out of the 249 (87.1%) stated that the tool allowed to explain extensively the BTP problem. Physician-patient correlation tests about baseline BTP intensity and BTP relief by medication showed statistical significance at the level of p = 0.001 and p = 0.0001, respectively. Evaluation of the efficacy of BPT medication revealed a 78.2% of patients declaring a good relief from BTP, with a significant reduction of mean BTP numeric rating scale score (p = 0.0001), but only 55.9% of patients responded to be satisfied about time for onset of the relief. CONCLUSIONS: In this study, ABPAT resulted to be a well-accepted tool for BTP assessment and characterization in a relatively large cohort of cancer patients. It is effective in discovering the unmet needs of cancer patients and in exploring the outcomes of BTP treatment.

Simple lifestyle recommendations and the outcomes of gestational diabetes. A 2 × 2 factorial randomized trial.

The benefits of exercise and behavioural recommendations in gestational diabetes mellitus (GDM) are controversial. In a randomized trial with a 2 × 2 factorial design, we examined the effect of exercise and behavioural recommendations on metabolic variables, and maternal/neonatal outcomes in 200 GDM patients. All women were given the same diet: group D received dietary recommendations only; group E was advised to briskly walk 20-min/day; group B received behavioural dietary recommendations; group BE was prescribed the same as B + E. Dietary habits improved in all groups. In a multivariable regression model, fasting glucose did not change. Exercise, but not behavioural recommendations, was associated with the reduction of postprandial glucose (p < 0001), glycated haemoglobin (HbA1c; p < 0.001), triglycerides (p = 0.02) and C-reactive protein (CRP; p < 0.001) and reduced any maternal/neonatal complications (OR = 0.50; 95%CI=0.28-0.89;p = 0.02). In GDM patients a simple exercise programme reduced maternal postprandial glucose, HbA1c, CRP, triglycerides and any maternal/neonatal complications, but not fasting glucose values.

Prediction of mortality and macrovascular complications in type 2 diabetes: validation of the UKPDS Outcomes Model in the Casale Monferrato Survey, Italy.

AIMS/HYPOTHESIS: The United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model can be used to estimate the lifetime occurrence of major diabetes-related complications in order to calculate health economic outcomes. The aim of the study was to assess the performance of the model by comparing the predicted and observed mortality and the incidence of macrovascular complications in an Italian population-based cohort with type 2 diabetes. METHODS: We used data from the Casale Monferrato Survey, a cohort enrolled in 1988 and surveyed in 1991 (n = 1,967) to assess the prevalence of cardiovascular risk factors. In 2000, a new survey included all the members of the original cohort who were still alive (n = 860), and in addition all individuals identified with a new diagnosis of type 2 diabetes since 1993 (n = 2,389). We compared the mortality predicted by the model for the 1991 survey over the subsequent 17-year period with the observed risk. The following outcomes were analysed in the 2000 survey: myocardial infarction (MI), other ischaemic heart disease, stroke, congestive heart failure (CHF) and amputation. RESULTS: For all-cause mortality, the predictions from the model at 5 and 10 years (23% and 47%, respectively) were identical to the observed risks. At 15 years, the risk of death was slightly overestimated (an estimate of 67% vs 64% observed, 95% CI 61%, 66%). The performance of the model was best for patients with a recent history of disease (duration <6 years). Among the complications, the predicted cumulative incidences of MI and CHF were very close to those observed. CONCLUSIONS/INTERPRETATION: External validation is essential to assess the accuracy of simulation models. The UKPDS Outcomes Model satisfactorily predicted a set of actual incidences of mortality and complications in an Italian diabetes cohort up to a duration of approximately 12 years. The longer term performance of such models should be carefully evaluated.

Cancer mortality reduction and metformin: a retrospective cohort study in type 2 diabetic patients.

AIMS: Few studies suggest that metformin decreases cancer mortality in type-2 diabetic patients (T2DP). We explored the association between the type and duration of antidiabetic therapies and cancer and other-than-cancer mortality in a T2DP cohort, taking into account the competing risks between different causes of death and multiple potential confounding effects. The mortality rates were compared with the general population from the same area. METHODS: In 1995, all T2DP (n = 3685) at our diabetes clinic in Turin (∼12% of all T2DP in the city), without cancer at baseline, were identified. Vital status was assessed after a mean 4.5-year follow-up. RESULTS: Metformin users had greater adiposity, while insulin users had more co-morbidities. All-cause- and cancer-related deaths occurred in: 9.2 and 1.6% of metformin users, 13.1 and 3.0% of sulfonylureas users and 26.8 and 4.8% of insulin users, respectively. In a Cox regression model for competing risks, adjusted for propensity score, metformin users showed a lower cancer mortality risk [hazard ratio (HR) = 0.56; 95% confidence interval (CI) 0.34-0.94], while insulin was positively associated with other-than-cancer mortality (HR = 1.56; 95%CI 1.22-1.99). Each 5-year metformin exposure was associated with a reduction in cancer death by 0.73, whereas every 5-year insulin exposure was associated with 1.25-fold increase in other-than-cancer death. Standardized mortality ratios for cancer and other-than-cancer mortality in metformin users were 43.6 (95%CI 25.8-69.0) and 99.1 (95%CI 79.3-122.5), respectively, in comparison with the general population. CONCLUSIONS: Metformin users showed a lower risk of cancer-related mortality than not users or patients on diet only; this may represent another reason to choose metformin as a first-line therapy in T2DP.

The rs553668 polymorphism of the ADRA2A gene predicts the worsening of fasting glucose values in a cohort of subjects without diabetes. A population-based study.

AIMS: Single-nucleotide polymorphisms in the human ADRA2A gene have been associated with increased risk of Type 2 diabetes. The associations between the rs553668 polymorphism and fasting glucose concentrations both cross-sectionally and longitudinally after 6-year follow-up were evaluated in an adult Caucasian population-based cohort. METHODS: From a cohort of 1658 individuals, after excluding patients with diabetes, those who died and those whose blood samples were not available for genotyping, data of 1345 individuals were analysed. RESULTS: Subjects homozygous for the A allele showed significantly increased baseline fasting glucose values and a significant worsening of fasting glucose (ß = 0.48; 95% CI 0.10-0.86) and insulin secretion (ß =-20.75; -32.67 to -8.82 for homeostasis model assessment for ß-cell function) at follow-up by using generalized estimating equations. Incidence of impaired fasting glucose and diabetes was almost twofold higher in subjects homozygous for the A allele (respectively: incident impaired fasting glucose 7.6-8.2, 16.1%, incident diabetes 1.7-2.3, 3.2% in GG, AG, AA carriers). CONCLUSIONS: Our results suggested that the rs553668 polymorphism is associated with glucose worsening in subjects without diabetes at baseline.

What predicts the occurrence of the metabolic syndrome in a population-based cohort of adult healthy subjects?

BACKGROUND: Metabolic syndrome (MS), the concurrence of hyperglycaemia, dyslipidaemia, hypertension and visceral obesity, increases cardiovascular risk and mortality. Predictors of MS were previously evaluated in patients without the full syndrome, but with some of its traits. This might confound the resulting associations. METHODS: The relationship between baseline variables and MS development was evaluated in healthy middle-aged subjects without any MS component at baseline, over a 4.5-year follow-up. RESULTS: From a population-based cohort of 1658 subjects, 241 individuals showed no MS components and 201 (83.4%) of them participated in a follow-up screening. At baseline, patients who developed the MS (n = 28/201; 13.9%) showed significantly higher Homeostasis Model Assessment-Insulin Resistance score (HOMA-IR) and C-reactive protein (CRP) values, and lower exercise level than subjects who did not. In a multiple logistic regression analysis, after multiple adjustments, the only baseline variable significantly (p < 0.01) associated with the MS was CRP (OR = 4.05; 95% CI 2.23-7.38; p < 0.001). Results did not change after adjusting for weight gain. The area under the receiver-operating curve was 0.83 for CRP after multiple adjustments. The optimal cut-off point of baseline CRP values was 2.1 mg/L, with 86% (95% CI 81-90) sensitivity and 75% (69-81) specificity in predicting the MS. Baseline CRP resulted associated with after-study glucose values in a multiple regression model (beta = 0.14; 0.08-0.20; p < 0.001). CONCLUSIONS: Higher baseline CRP values confer a significant increased risk of developing the MS in healthy subjects, independently of weight gain.

Appropriateness of early breast cancer management in relation to patient and hospital characteristics: a population based study in Northern Italy.

Administrative data may provide valuable information for monitoring the quality of care at population level and offer an efficient way of gathering data on individual patterns of care, and also to shed light on inequalities in access to appropriate medical care. The aim of the study was to investigate the role of patient and hospital characteristics in the initial treatment of early breast cancer using administrative data. Incident breast cancer patients were identified from hospital discharge records and linked to the radiotherapy outpatient database during 2000-2004 in the Piedmont region of Northwestern Italy. Women treated with breast-conserving surgery followed by radiotherapy (BCS + RT) were compared to those treated with BCS without radiotherapy (BCS w/o RT) or mastectomy using multinomial logistic regression models. Out of 16,022 incident cases, 46.2% received BCS + RT, 20.3% received BCS w/o RT, and 33.5% received a mastectomy. Compared to BCS + RT, the factors associated with BCS w/o RT were: increased age (OR = 1.54; 95% CI = 1.29-1.85, for ages 70-79 vs. <50), being unmarried (1.24; 1.13-1.36), presence of co-morbidities (1.32; 1.10-1.58), being treated at hospitals with low surgical volume (1.31; 1.07-1.60 for hospitals with less than 50 vs. > or =150 interventions/year), and living far from radiotherapy facilities (1.75; 1.39-2.20 for those at a distance of >45 min). These same factors were also associated with mastectomy. During the 5-year period observed, there was a trend of reduced probability of receiving a mastectomy (0.70; 0.56-0.88 for 2004 vs. 2000). The presence or absence of nodal involvement was positively associated with mastectomy (2.28; 1.83-2.85) and negatively associated with BCS w/o RT (0.65; 0.56-0.76). After adjustment for potential confounders, education level did not show any association with the type of treatment. Social and geographical factors, in addition to hospital specialization, should be considered to reduce inappropriateness of care for breast cancer.

Multidimensional geriatric assessment in treatment decision in elderly cancer patients: 6-year experience in an outpatient geriatric oncology service.

This prospective cohort study of consecutive elderly cancer patients was undertaken to evaluate the role of the multidimensional geriatric assessment (MGA) as an aid in treatment decision-making. A total of 571 cancer patients (aged > or =70) were enrolled during 6-year (1999-2005). All underwent MGA as part of the first evaluation. In multivariate analysis, the probability of receiving active, instead of palliative, treatment was negatively associated with increasing age (odds ratio=0.69 every 5 years, p=0.005), living alone (OR=0.54, p=0.031), dependence in activities of daily living (ADL score >0, OR=0.41, p=0.003) and a low body-mass index (BMI) (OR=0.51, p=0.061); while a positive association emerged for instrumental activities of daily living (IADL) score (OR=1.12 per point, p=0.019). Our data suggest that MGA, in addition to age, is a useful tool in clinical practice for deciding cancer treatment in elderly patients, with a major independent role played by living alone, ADL, IADL and BMI.

Is three-dimensional power Doppler ultrasound useful in the assessment of placental perfusion in normal and growth-restricted pregnancies?

OBJECTIVES: To investigate three-dimensional (3D) power Doppler ultrasound indices in the assessment of placental perfusion and their relationship to gestational age (GA), placental position and umbilical artery Doppler flow velocity waveform (FVW) patterns in normal and intrauterine growth-restricted (IUGR) pregnancies. METHODS: Forty-five pregnant women at 23-37 weeks' gestation were studied, of whom 30 had IUGR and 15 were controls. Nine of the IUGR group had normal umbilical FVWs (NED), nine had abnormal patterns but positive end-diastolic velocities (PED) and 12 had absent or reversed end-diastolic velocities (AED). Placental position was assessed as being posterior, anterior or lateral. 3D power Doppler indices related to placental perfusion (vascularization index (VI), vascularization flow index (VFI) and flow index (FI)) were obtained from five different sampling sites in each placenta. RESULTS: VI, VFI and FI were not significantly dependent on GA or placental position. VI and VFI were significantly lower in PED and AED cases compared with controls, while FI was reduced in the AED group only. VI and VFI showed high variability between different sampling sites within each placenta, while the variability of FI was much lower. CONCLUSIONS: 3D power Doppler sonography can provide new insights into placental pathophysiology. FI, which identifies the most severe cases of placental impairment, appears to be the most reliable index because of its low intraplacental variability. Further studies are needed to verify its accuracy when applied in clinical practice as a substitute for or an adjunct to umbilical artery Doppler studies.

Prolonged survival in poor-risk diffuse large B-cell lymphoma following front-line treatment with rituximab-supplemented, early-intensified chemotherapy with multiple autologous hematopoietic stem cell support: a multicenter study by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi).

A prospective multicenter program was performed to evaluate the combination of rituximab and high-dose (hd) sequential chemotherapy delivered with multiple autologous peripheral blood progenitor cell (PBPC) support (R-HDS-maps regimen) in previously untreated patients with diffuse large B-cell lymphoma (DLB-CL) and age-adjusted International Prognostic Score (aaIPI) score 2-3. R-HDS-maps includes: (i) three APO courses; (ii) sequential administration of hd-cyclophosphamide (CY), hd-Ara-C, both supplemented with rituximab, hd-etoposide/cisplatin, PBPC harvests, following hd-CY and hd-Ara-C; (iii) hd-mitoxantrone (hd-Mito)/L-Pam + 2 further rituximab doses; (iv) involved-field radiotherapy. PBPC rescue was scheduled following Ara-C, etoposide/cisplatin and Mito/L-Pam. Between 1999 and 2004, 112 consecutive patients aged <65 years (74 score 2, 38 score 3) entered the study protocol. There were five early and two late toxic deaths. Overall 90 patients (80%) reached clinical remission (CR); at a median 48 months follow-up, 87 (78%) patients are alive, 82 (73%) in continuous CR, with 4 year overall survival (OS) and event-free survival (EFS) projections of 76% (CI 68-85%) and 73% (CI 64-81%), respectively. There were no significant differences in OS and EFS between subgroups with Germinal-Center and Activated B-cell phenotype. Thus, life expectancy of younger patients with aaIPI 2-3 DLB-CL is improved with the early administration of rituximab-supplemented intensive chemotherapy compared with the poor outcome following conventional chemotherapy.

Telomere length identifies two different prognostic subgroups among VH-unmutated B-cell chronic lymphocytic leukemia patients.

Some evidences suggest that telomere restriction fragment length (TRF-L) is an effective indicator of histopathogenesis in B-cell tumors. As histopathogenesis is relevant for B-cell chronic lymphocytic leukemia (B-CLL) prognosis, TRF-L was assessed by Southern blot in 201 patients and compared to variable immunoglobulin heave chain gene mutational status (VH-MS) and to other known prognostic features. Overall survival (OS), time to first treatment (TTFT) and progression-free survival (PFS) were evaluated. Our results indicate the following: (1) TRF-L is heterogeneous among B-CLL patients (median 6014 bp, range 1465-16 762); (2) TRF-L correlates to VH-MS (r(2)=0.1994, P<0.0001) with VH-mutated patients showing long and VH-unmutated short telomeres; however, 41% of VH-unmutated and 5% of VH-mutated patients did not show this correlation and were thus defined as 'discordant'; (3) TRF-L effectively predicts outcome in terms of TTFT, PFS and OS; (4) VH-unmutated discordant patients have a better clinical outcome than VH-unmutated concordant patients (OS P<0.01, PFS P<0.05) and similar to that of VH-mutated patients (OS, PFS P=NS). Compared to VH-unmutated concordant patients, VH-unmutated discordant patients showed no peculiarity in their immunoglobulin rearrangement nor in their flow cytometry or fluorescence in situ hybridization profile. In conclusion, TRF-L can be helpful to refine prognostication of B-CLL patients, particularly those with a VH-unmutated immunoglobulin sequence.

Evaluating hospital costs in type 2 diabetes care: does the choice of the model matter?

BACKGROUND: Awareness of the economic burden of diabetes has led to a number of studies on economic issues. However, comparison among cost-of-illness studies is problematic because different methods are used to arrive at a final cost estimate. OBJECTIVE: The aim of the study is to show how estimates of hospitalisation costs for diabetic patients can vary significantly in relation to the statistical method adopted in the analysis. RESEARCH DESIGN AND METHODS: The study analyses diabetic patients' costs as a function of demographic and clinical covariates, by applying the following statistical survival models: the parametric survival model assuming Weibull distribution, the Cox proportional hazard (PH) model and the Aalen additive regression for modelling costs. The Aalen approach is robust both for the non proportionality in hazard and for departures from normality. In addition it is able to easily model the effect of covariates on the extreme costs. This cost analysis is based on data collected for a retrospective observational study analysing repeated hospitalisations (N = 4816) in a cohort of 3892 diabetic patients. RESULTS: There is agreement in all models with the effects of the considered covariates (age, sex, duration of disease and presence of other pathologies). An effect of over- or under-estimation, according to the chosen model due to arguably inappropriate model fitting, was observed, being more evident for some specific profiles of the patients, and overall accounting for as much as 20% of the estimated effect. The Aalen model was able to cope with all the other models in furnishing unbiased estimates with the advantage of a greater flexibility in representing the covariates' effect on the cost process. CONCLUSIONS: An appropriate choice of the model is crucial in avoiding misinterpretation of cost determinants of type 2 diabetes care. For our data set the Aalen model proved itself to be a realistic and informative way to characterise the effect of covariates on costs.