Life Satisfaction in a Sample of Outpatients with Severe Mental Disorders: A Survey in Northern Italy

This paper presents a cross-sectional survey of subjective quality of life in a sample of 40 Italian patients with disabling mental disorders living in the community. The patients self-rated their quality of life by the Satisfaction with Life Domains Scale. They were satisfied in relation to basic needs, such as housing, food or clothing and appreciated to some extent the services received, but were very unhappy about their income and their intimate sexual relationships. This Italian sample appeared less satisfied than most samples of people with severe mental disorders investigated by the same instrument in other countries. This may be related to the high level of psychopathology and disability shown by patients for whom survival in the community is in itself an achievement. However, lack of money and poor sexual life are common concerns of long-term mentally ill. How to address such problems is a major challenge for community psychiatric services.     

Is the alpha-beta ratio of prostate cancer really low? A prospective, non-randomized trial comparing standard and hyperfractionated conformal radiation therapy.

BACKGROUND AND PURPOSE: The objectives of the current study were to compare genito-urinary (GU) and gastro-intestinal (GI) toxicities as well as biochemical control (bRFS) in prostate cancer, utilizing conventional (2.0 Gy daily) (STD) or hyperfractionated (HFX) conformal irradiation (CRT). HFX (1.2 Gy BID) was chosen as a radiobiological method to try to reduce long term sequelae without compromising local control. PATIENTS AND METHODS: Three-hundred-and-seventy consecutive patients (pts) entered this prospective, non-randomized trial in the period January 1993-January 2003; 209 were treated with STD and 161 with HFX CRT. All were evaluable for acute toxicity analysis, 179 (STD) and 151 pts (HFX) being evaluable for late sequelae and bRFS analyses. Pt characteristics were not statistically different in the two groups. CRT consisted of a 4-field technique for prostate and/or pelvic nodes and a 5-field boost with rectal shielding. Median doses were 74 and 79.2 Gy for STD and HFX patients respectively, the latter dose being isoeffective for tumour control assuming alpha/beta=10 (EQD(2)=73.9 Gy). Median follow-up was 29.4 months (25.2 mos for STD; 37.7 mos for HFX; P<0.01). The two regimens were compared in terms of acute and late GU and GI toxicities and 5-year bRFS by univariate and multivariate analyses. RESULTS: Acute grade> or =2 GU toxicity was higher in the STD group (48.6% versus 37.3% in HFX, P=0.03), while no significant difference was found for acute GI toxicity. Late grade> or =2 GU and GI toxicities were lower in the HFX group (5-year actuarial rate: GU: 10.1% versus 20.3%, P=0.05; GI: 6.0% versus 10.6%, P=0.18). Five-year bRFS were 70% (+/-13.8%, 95% CI) and 82.6% (+/-7.2%) for STD and HFX, respectively (P=0.44); a trend favouring HFX was found in the subgroup of pts who did not receive hormonal therapy (5-year bRFS: 85.9%+/-12.4% versus 63.9%+/-23.8%, P=0.15). Multivariate analysis revealed only risk groups and age statistically related to bRFS but not fractionation regimen. Using the Nahum-Chapman TLCP model and prostate parameter set, which includes hypoxia, the TLCPs are approximately equal for the two regimens, whereas assuming alpha/beta=1.5 and no hypoxia we obtain 73% for the STD group but only 36% for the HFX group. CONCLUSIONS: As expected from radiobiological considerations, HFX reduces GI and GU late toxicities. Concerning early bRFS, our clinical findings suggest that HFX is no less effective than STD when delivering an isoeffective (alpha/beta=10) dose. Despite the relatively short follow-up, this result appears to be inconsistent with a low alpha/beta ratio for prostate cancer.     

Variability in tablet fragment weights when splitting unscored cyclobenzaprine 10 mg tablets.

OBJECTIVE: To determine the weight variation and calculated dosing variability of tablet fragments upon splitting unscored cyclobenzaprine hydrochloride 10 mg tablets using two common tablet splitting devices. DESIGN: Comparative pharmaceutics study. SETTING: Pharmacy school laboratory. PARTICIPANTS: Not applicable. INTERVENTIONS: Unscored cyclobenzaprine hydrochloride 10 mg tablets from one generic manufacturer were split with a tablet splitter or a kitchen knife by a licensed pharmacist and two doctor of pharmacy students (n = 15 tablets for each method per participant). MAIN OUTCOME MEASURES: Fragment weights (FWs) were compared with the theoretical weights (TWs), which were calculated as one half of the mean weight of the tablets used in each part of the experiment; means, relative standard deviations (RSDs), and percentages of TW were also calculated. RESULTS: The mean weight before splitting the 45 tablets with the tablet splitter was 136.6 +/- 2.1 mg (TW = 68.3 mg). The mean FW after splitting was 67.9 +/- 7.9 mg. The RSD of 11.6% corresponded to a range of 69.4% to 130.2% of the TW and an estimated drug content of the split fragments between 3.47 mg and 6.51 mg. The mean weight before splitting the 45 tablets cut with a kitchen knife was 136.6 +/- 2.0 mg (TW = 68.3 mg). The mean FW was 68.0 +/- 15.7 mg with a RSD of 23.2%, corresponding to a range of 49.9% to 149.5% of the TW and an estimated drug content of the split fragments between 2.49 mg and 7.48 CONCLUSION: Tablet fragments obtained after splitting this generic cyclobenzaprine 10 mg product varied considerably in weight and estimated drug content. Accordingly, splitting cyclobenzaprine 10 mg tablets to achieve 5 mg doses could result in unpredictable dosing and therapeutic response.     

Metformin Decreases Circulating Androgen and Estrogen Levels in Nondiabetic Women With Breast Cancer

IntroductionDiabetic patients treated with metformin have a lower risk of developing BC or a better BC prognosis. Metformin might reduce cancer growth through direct antiproliferative effects or through indirect mechanisms, particularly the reduction of insulin. In a randomized study on nondiabetic BC patients in natural menopause with high testosterone levels, we observed a significant decrease in insulin and in testosterone levels with metformin 1500 mg/d compared with 1000 mg/d. We present the results of a new analysis of our study on the effect of metformin on the bioavailability of sex hormones.Patients and MethodsOne hundred twenty-four eligible women were initially invited to take metformin 500 mg/d for 3 months. The 108 women who completed the first 3 months continued the study using 1000 mg/d for 1 month. The women were then randomized into 2 groups, and, for the subsequent 5 months, 1 group increased the dose to 1500 mg/d, and the other group continued with 1000 mg/d.ResultsNinety-six women completed the study, 43 receiving metformin 1500 mg/day, and 53 receiving 1000 mg/day. The women receiving 1500 mg/d showed a greater and significant reduction of free testosterone (?29%) and estradiol (?38%), a borderline significant reduction of estrone and insulin-like growth factor-1, and a nonsignificant reduction of androstenedione. They also showed a nonsignificant increase of dehydroepiandrosterone sulfate.ConclusionMetformin does not interfere with the production of dehydroepiandrosterone sulfate. Besides, it decreases estradiol levels, basically through the reduction of testosterone. These hormonal changes might have clinical relevance.     

Executive functions in intellectual disabilities: A comparison between Williams syndrome and Down syndrome

Executive functions are a set of high cognitive abilities that control and regulate other functions and behaviors and are crucial for successful adaptation. Deficits in executive functions are frequently described in developmental disorders, which are characterized by disadaptive behavior. However, executive functions are not widely examined in individuals with intellectual disability. The present study is aimed at evaluating the etiological specificity hypotheses pertaining to executive functions by comparing individuals with intellectual disability of different etiology, as Williams syndrome and Down syndrome, on different aspects of executive functions. To this aim a battery evaluating attention, short-term and working memory, planning, categorization, shifting and inhibition, was administered to 15 children, adolescents and adults with Williams syndrome, to 15 children, adolescents and adults with Down syndrome and to 16 mental-age-matched typically developing children. The two groups with intellectual disability showed impairment in a set of executive functions, as auditory sustained attention, visual selective attention, visual categorization and working memory, and preserved visual sustained attention, auditory selective attention and visual inhibition. However, a distinctive profile has been found between the two syndromic groups on other executive functions. While participants with Down syndrome were poor in shifting and verbal aspects of memory and inhibition, those with Williams syndrome were poor in planning. The specific weakness and straights on executive functions may support the etiological specificity hypothesis accounting for distinctive cognitive development syndrome-specific.     

Prognostic impact of HER-2/neu expression on squamous head and neck carcinomas

BACKGROUND: HER-2/neu gene amplification and protein overexpression have been identified in various solid tumors, but its prognostic relevance in head and neck squamous cell carcinoma (HNSCC) is still controversial. METHODS: The study investigated the expression of HER-2/neu oncoprotein in HNSCC and sought possible correlations to various clinicopathologic parameters. Expression of HER-2/neu oncoprotein was assessed in archival tumor tissues from 87 untreated HNSCC patients by immunohistochemical technique. Data were correlated with both the clinicopathologic parameters and patient survival. RESULTS: A high membranous HER-2/neu protein expression level was found in 39% of patients. Multivariate analysis indicated that HER-2/neu protein expression and pN lymph-node status were independent prognostic factors for disease-free survival. CONCLUSIONS: HER2/neu overexpression and its relationship with survival suggest that new therapeutic approaches targeting epidermal growth factor receptor (EGFR) family receptors could provide a new way of treating HNSCC patients with HER2/neu-positive neoplastic lesions.     

Exercise Performance of Chronic Heart Failure Patients in the Early Period of Support by an Axial‐Flow Left Ventricular Assist Device as Destination Therapy

Axial‐flow left ventricular assist devices (LVADs) are increasingly used as destination therapy in end‐stage chronic heart failure (CHF), as they improve survival and quality of life. Their effect on exercise tolerance in the early phase after implantation is still unclear. The aim of this study was to evaluate the effect of LVADs on the exercise capacity of a group of CHF patients within 2 months after initiation of circulatory support. Cardiopulmonary exercise test data were collected for 26 consecutive LVAD‐implanted CHF patients within 2 months of initiation of assistance; the reference group consisted of 30 CHF patients not supported by LVAD who were evaluated after an episode of acute heart failure. Both LVAD and reference groups showed poor physical performance; LVAD patients achieved lower workload (LVAD: 36.3 ± 9.0 W, reference: 56.6 ± 18.2 W, P < 0.001) but reached a similar peak oxygen uptake (peak VO₂; LVAD: 12.5 ± 3.0 mL/kg/min, reference: 13.6 ± 2.9 mL/kg/min, P = ns) and similar percentages of predicted peak VO₂ (LVAD: 48.8 ± 13.9%, reference: 54.2 ± 15.3%, P = ns). While the values of the O₂ uptake efficiency slope were 12% poorer in LVAD patients than in reference patients (1124.2 ± 226.3 vs. 1280.2 ± 391.1; P = ns), the kinetics of VO₂ recovery after exercise were slightly better in LVAD patients (LVAD: 212.5 ± 62.5, reference: 261.1 ± 80.2 sec, P < 0.05). In the first 2 months after initiation of circulatory support, axial‐flow LVAD patients are able to sustain a low‐intensity workload; though some cardiopulmonary exercise test parameters suggest persistence of a marked physical deconditioning, their cardiorespiratory performance is similar to that of less compromised CHF patients, possibly due to positive hemodynamic effects beginning to be produced by the assist device.