Effects of a diet integration with an oily emulsion of DHA-phospholipids containing melatonin and tryptophan in elderly patients suffering from mild cognitive impairment.

Age-related changes in nutritional status can play an important role in brain functioning. Specific nutrient deficiencies in the elderly may exacerbate pathological processes in the brain. Consequently, the potential of nutritional intervention to prevent or delay cognitive impairment and the development of dementia is an important topic. A randomized, double-blind, placebo-controlled trial has been performed in 25 elderly subjects (86 ± 6 years, 20 females, 5 males) with mild cognitive impairment (MCI). These subjects were randomly assigned to supplement their diet with either an oily emulsion of docosahexaenoic acid (DHA)-phospholipids containing melatonin and tryptophan (11 subjects) or a placebo (14-matched subjects) for 12 weeks. The main aim of this study was to evaluate the efficacy of the dietary supplement on cognition, by the assessment at the start and after 12 weeks of: (1) Orientation and other cognitive functions: Mini-Mental State Examination (MMSE); (2) Short-term memory: digit, verbal, and spatial span (digit span; verbal span; Corsi's test); (3) Long-term memory: Rey's auditory-verbal learning test; 'short story' test; Rey-Osterrieth complex figure (recall); (4) Attentional abilities: attentive matrices; (5) Executive functions: Weigl's sorting test; phonological fluency 'FAS'; (6) Visuo-constructional and visuo-spatial abilities: copy of simple drawings; Rey-Osterrieth complex figure (copy); (7) Language: semantic fluency; (8) Mood: Geriatric Depression Scale (GDS). Moreover, Sniffin' Sticks olfaction test and Mini Nutritional Assessment (MNA) have been performed. After 12 weeks, a significant treatment effect for the MMSE (P < 0.001) and a positive trend for the semantic verbal fluency was found in the supplement group (P < 0.06). A significant treatment effect was found out for the olfactory sensitivity assessment (P < 0.009). As regards the nutrition evaluation, after 12 weeks of treatment the supplemented group showed an improvement in the MNA score with a significant difference relative to placebo (P < 0.005). Older adults with MCI had significant improvements in several measures of cognitive function when supplemented with an oily emulsion of DHA-phospholipids containing melatonin and tryptophan for 12 weeks, compared with the placebo.

Clinical trial on the efficacy of a new symbiotic formulation, Flortec, in patients with acute diarrhea: a multicenter, randomized study in primary care.

OBJECTIVES: Few randomized studies have been carried out on adult patients affected by acute diarrhea especially in primary care, which is the natural context for this kind of disorder. Lactobacillus paracasei B 21060 is a novel strain of lactobacillus, which has been shown to be effective in relieving symptoms associated with diarrhea of irritable bowel syndrome subtype and in shortening diarrhea duration. In this study, we compared the therapeutic efficacy, safety, and tolerability of a new symbiotic formulation, Flortec, containing L. paracasei B-21060, with lactobacillus GG (FlorVis GG) in the treatment of acute presumed infectious diarrhea. METHODS: Fourteen general practitioners working in the Perugia health authority district carried out a randomized controlled, parallel-group, open trial in 174 adult patients suffering from acute diarrhea (87 enrolled in the Flortec group and 87 in the FlorVis group). Both the products were administered according to their standard recommended dosage. The main efficacy criterion was the duration of diarrhea after beginning treatment. Treatment duration was 10 days. Enrolled patients kept a careful track of their symptoms noting them in a personal diary for 12 days. RESULTS: The 2 groups resulted to be homogeneous at baseline with regard to prognostic variables. The mean duration of diarrhea from the start of treatment in the Flortec group was 4.24 (2.73 SD) days versus 5.09 (3.72 SD) days in the FlorVis group (P=0.09).Clinical success rates in terms of absence of abdominal pain and absence of diarrhea (defined as <2 bowel movements of watery or loose stool consistency) recorded at different time-points were statistically superior in the Flortec group (Kaplan-Meyer P=0.05 for both the symptoms). The physician judged that overall efficacy was good or very good in 91.8% of the patients in the Flortec group. The corresponding value in the FlorVis group was 83.7% (P=0.003). The 2 treatments showed a very good tolerability profile, with negligible and similar adverse event rates and similar concomitant medication usage rates. CONCLUSIONS: Oral therapy with Flortec proved to be more effective than FlorVis GG in the treatment of acute diarrhea in adults treated at a primary care setting.

Topical nifedipine with lidocaine ointment versus active control for pain after hemorrhoidectomy: results of a multicentre, prospective, randomized, double-blind study.

BACKGROUND: Spasm through the internal anal sphincter is one of the supposed causes for pain after hemorrhoidectomy, a common and distressing experience. We hypothesized that the addition of topical nifedipine to lidocaine would improve pain control by causing a relaxation of the smooth muscle of the internal anal sphincter. METHODS: We conducted a multicentre randomized, double-blind trial to compare the efficacy of 0.3% nifedipine and 1.5% lidocaine ointment versus 1.5% lidocaine ointment alone in reducing pain after hemorrhoidectomy. A physician unaware of the treatment arm measured pain by use of the Analogue Chromatic Continuous Scale (ACCS) at baseline; soon after surgery; at 2, 4, 6, 8 and 24 hours after surgery; on day 7 after surgery; and at a final visit 14 days after surgery. The physician also noted the time to first analgesic administration within 24 hours after surgery. RESULTS: In all, 135 patients per group participated (270 total). Evaluation of the delta ACCS score versus basal value, a covariate for rescue analgesic administration time, revealed better pain control in the group that received nifedipine with lidocaine at 6 hours after surgery and on day 7 (p < 0.011 and p < 0.054, respectively). We noticed no difference between groups for time of administration of rescue analgesic, blood pressure, heart rate or frequency of headache. CONCLUSION: Although there was no difference between groups for time of administration of rescue analgesic after open hemorrhoidectomy, the patients' assessment of pain using ACCS showed that the use of topical nifedipine with lidocaine may provide a slight significant difference in favour of the study group at 6 hours and at day 7 after surgery. Narcotic analgesics and nonsteroidal anti-inflammatory drug administration should continue to be recommended. Further research focusing on these outcomes is warranted.

Pharmacokinetics of anorectal nifedipine and lidocaine (lignocaine) ointment following haemorrhoidectomy: an open-label, single-dose, phase IV clinical study.

OBJECTIVES: This study aimed to assess whether topical anorectal application of an ointment containing nifedipine (0.3% w/w) and lidocaine (lignocaine) [1.5% w/w] to patients undergoing Milligan-Morgan haemorrhoidectomy achieves pharmacologically relevant serum concentrations of the active ingredients and has any haemodynamic effects or adverse effects. METHODS: A single dose of 3 g of study ointment was circumferentially applied inside the anus to 24 patients (17 males and 7 females) aged 23-71 years (mean +/- SD: 42.9 +/- 4.9 years) during postoperative dressing after Milligan-Morgan haemorrhoidectomy from March 2007 to January 2008. Blood samples for the determination of nifedipine and lidocaine serum concentrations were drawn before surgery and at 20, 40, 60, 90, 120, 240, 360, 480 and 720 minutes after application. Serum concentrations of nifedipine and lidocaine were determined by a high-performance liquid chromatography method in order to calculate pharmacokinetic parameters. Patients' BP, heart rate and ECG readings were monitored during the study. RESULTS: Chromatographic signals of nifedipine were sporadically observed in only five patients (20.8%), consistent with therapeutically negligible concentrations and insufficient to permit calculation of any pharmacokinetic parameters. The serum concentrations of nifedipine in these five patients ranged from 5.9 to 18.8 ng/mL. Lidocaine concentrations were detectable in all patients. The means +/- SD and medians of pharmacokinetic parameters for lidocaine were as follows: maximum serum concentration (C(max)) 245.1 +/- 370.8 ng/mL, 73.6 ng/mL; time to reach C(max) (t(max)) 69.2 +/- 78.3 minutes, 40 minutes; area under the serum concentration-time curve from 0 to 6 hours (AUC(6)) 756.5 +/- 1254.1 ng.h/mL, 238.2 ng.h/mL. Only three patients had maximum serum concentrations above 1000 ng/mL (1037.8, 1044.75 and 1364.1 ng/mL). These outlier concentrations were four to five times lower than the threshold of CNS lidocaine toxicity (5000-6000 ng/mL). No serious local or systemic adverse events were observed throughout the study, and no subjects developed arrhythmias or significant ECG changes. Neither BP nor mean heart rate varied significantly after application of a single dose. CONCLUSIONS: This study demonstrates that single-dose topical application of an ointment containing nifedipine (0.3% w/w) and lidocaine (1.5% w/w) to patients undergoing Milligan-Morgan haemorrhoidectomy is safe to use. Following application onto damaged anorectal mucosa, nifedipine and lidocaine are absorbed into the bloodstream in small quantities that do not have any major implications for the safety of the product. Further studies are required to evaluate nifedipine and lidocaine concentrations in serum using a multiple-dose regimen.

Functional disability in early Alzheimer's disease - a validation study of the Italian version of the disability assessment for dementia scale.

AIM: To determine the applicability and psychometric properties of the Italian version of the Disability Assessment of Dementia scale (DAD-I) in a community-residing population with early-stage Alzheimer's disease (AD). METHODS: The DAD-I was administered to the primary caregivers of 159 patients (mean age +/- SD 77.1 +/- 5.2) with mild AD (mean Mini Mental State Examination, MMSE, +/- SD 23.1 +/- 2.2). RESULTS: The DAD-I showed excellent internal consistency reliability (Cronbach's alpha = 0.92) and good construct validity. The DAD-I score was not significantly associated with gender, education and presumed duration of the illness, and had a low negative correlation with age. The DAD-I score correlated moderately with the traditional Instrumental Activities of Daily Living and Activities of Daily Living scales, respectively, with r = 0.53 and r = 0.54 (p < 0.0001). Relatively low, but statistically significant correlations (r ranging between 0.21 and 0.31) with the MMSE were also found. CONCLUSION: The DAD-I was found to be a reliable and valid instrument to assess functional disability in community-dwelling Italian subjects with early-stage AD.

Clinical trial on the efficacy of a new symbiotic formulation, Flortec, in patients with irritable bowel syndrome: a multicenter, randomized study.

OBJECTIVES: Efficacy of symbiotics in patients with irritable bowel syndrome (IBS) remains unknown. METHODS: Patients were randomized to a prebiotic (n=135), or a symbiotic formulation containing Lactobacillus paracasei B21060 (Flortec, n=132). Primary efficacy was the responder rate for pain and global relief of symptoms in the overall population and in patients with predominant diarrhea (n=47). Post hoc time-trend analyses for changes within each treatment were carried out. RESULTS: Patients with absent/mild pain amounted to 54.7% in the symbiotic group and to 57.4% in the prebiotic group at treatment week 4, and to 53.9% and 53.4% at the end of treatment. Patients with amelioration of well-being were, respectively, 60.7% versus 61.7% at treatment week 4, and 63.3% versus 60.9% at the end of treatment. Within each treatment group, patients with absent/mild pain increased in the Flortec and the prebiotic group, but time trend analyses were significant only for Flortec (P=0.019). In IBS-predominant diarrhea, Flortec significantly reduced bowel movements, pain, and IBS scores. CONCLUSIONS: To improve pain and well-being, Flortec is encouraging in patients with diarrhea predominant IBS. To establish its efficacy for the majority of IBS patients, Flortec has to be compared with an inert placebo in future work.

Visuospatial planning and problem solving in Alzheimer's disease patients: a study with the Tower of London Test.

BACKGROUND: Executive dysfunction in Alzheimer's disease (AD) has been recently recognized as an early and prominent clinical sign. The Tower of London (ToL), a task specifically devised to test executive functions of visuospatial planning and problem solving, has frequently been used in neuropsychological experiments, but rarely in the clinical ground. METHODS: One hundred and sixty-one AD patients and 212 nondemented healthy controls were administered a simplified ToL version. RESULTS: AD patients were significantly impaired (p < 0.0001) in all ToL scores and in the total execution time. The 'accuracy' score of ToL at a cut off of

Development and validation of the short version of the Psychological General Well-Being Index (PGWB-S).

BACKGROUND: The PGWBI is a 22-item health-related Quality of Life (HRQoL) questionnaire developed in US which produces a self-perceived evaluation of psychological well-being expressed by a summary score. The PGWBI has been validated and used in many countries on large samples of the general population and on specific patient groups. Recently a study was carried out in Italy to reduce the number of items of the original questionnaire, yielding the creation of a shorter validated version of the questionnaire (PGWB-S). The purpose of the present paper is to describe the methods adopted and to report and discuss the relevance of results. METHODS: Data for this study were collected from 4 different population samples: two general population samples a student and a patient sample. On the basis of the results of the first (development) sample population, six relevant items were identified statistically from the original questionnaire and grouped to assemble a new summary scale. Following the newly created 6-item questionnaire was administered in three independent population samples. Descriptive statistics, correlation coefficients, univariate and multivariate regression analyses were used to compare the performance of the long and short questionnaire, within and between population samples and across relevant subgroups. A further independent sample extracted by an ongoing cancer clinical trial served as final validation step. RESULTS: Overall, the questionnaires were administered to 1443 subjects. Six items were selected by a step-wise approach to explain 90% of the variance of the summary measure of the original questionnaire. Response rates reached 100%, while missing items were not observed. University students (n = 400) showed the highest mean value of the summary measure (75.3); while the patient sample (n = 28) had the lowest score (71.5). The correlation coefficients between the summary measures and the single items according to the different studies were satisfactory, reaching the highest estimates in the student sample. The internal consistency showed high values of the Cronbach's alpha coefficient (range 0.80-0.92) for all three study samples, coming close to the value of the coefficient established for the original questionnaire (0.94). A cross-validation in an independent sample of 755 cancer patients confirmed the item selection procedure and amount of variance explained by the new shorter questionnaire (ranging from 90. 2 to 95.1 %, across age and sex strata). CONCLUSION: The newly identified PGWB-S showed good acceptability and validity for the use in various settings in Italy. The translation of the PGWB-S into different languages, and its use in other linguistic settings will add evidence about its cross-cultural validity.

Tower of London test: a comparison between conventional statistic approach and modelling based on artificial neural network in differentiating fronto-temporal dementia from Alzheimer's disease.

The early differentiation of Alzheimer's disease (AD) from frontotemporal dementia (FTD) may be difficult. The Tower of London (ToL), thought to assess executive functions such as planning and visuo-spatial working memory, could help in this purpose. Twentytwo Dementia Centers consecutively recruited patients with early FTD or AD. ToL performances of these groups were analyzed using both the conventional statistical approaches and the Artificial Neural Networks (ANNs) modelling. Ninety-four non aphasic FTD and 160 AD patients were recruited. ToL Accuracy Score (AS) significantly (p < 0.05) differentiated FTD from AD patients. However, the discriminant validity of AS checked by ROC curve analysis, yielded no significant results in terms of sensitivity and specificity (AUC 0.63). The performances of the 12 Success Subscores (SS) together with age, gender and schooling years were entered into advanced ANNs developed by Semeion Institute. The best ANNs were selected and submitted to ROC curves. The non-linear model was able to discriminate FTD from AD with an average AUC for 7 independent trials of 0.82. The use of hidden information contained in the different items of ToL and the non linear processing of the data through ANNs allows a high discrimination between FTD and AD in individual patients.