Patient and physician views on the quality of care for inflammatory bowel disease after one-year follow-up: Results from SOLUTION-2, a prospective IG-IBD study.

BACKGROUND AND AIMS: Perception of quality of care is important in the management of patients with chronic diseases, particularly inflammatory bowel disease. AIMS AND METHODS: This longitudinal study aimed to investigate variations of the Quality of Care through the Patients' Eyes (QUOTE-IBD) questionnaire scores one year after the basal evaluation in the Studio Osservazionale quaLità cUre malatTIe crOniche intestiNali (SOLUTION-1) study. RESULTS: Of the cohort of 992 patients, 936 were evaluable. The QUOTE-IBD score overcame satisfactory levels of more than the 80%, overall and in all subdomains except for the "Continuity of Care" sub-dimension (mean, 8.3; standard deviation, 1.49), scored satisfactory only by 34% of the patients. No significant changes in satisfaction were recorded overall, or considering patients subgroups. Significant differences were found at the end of the follow-up between physicians' and patients' perceptions of quality of care, with the former over-rating their performance in "Continuity of Cares" and under-rating "Costs", "Competence", and "Accessibility" sub-domains of the score (p<0.05 for all). CONCLUSION: Perceived quality of care in a large cohort of Italian patients with inflammatory bowel disease remains unchanged after one-year follow-up and was not significantly affected by disease activity or therapeutic interventions. Differences between physicians' and patients' perceptions of quality of care should be taken into account.

L-Dopa Pharmacokinetic Profile with Effervescent Melevodopa/Carbidopa versus Standard-Release Levodopa/Carbidopa Tablets in Parkinson's Disease: A Randomised Study.

Objectives. To characterize the pharmacokinetic profile of levodopa (L-dopa) and carbidopa after repeated doses of the effervescent tablet of melevodopa/carbidopa (V1512; Sirio) compared with standard-release L-dopa/carbidopa in patients with fluctuating Parkinson's disease. Few studies assessed the pharmacokinetics of carbidopa to date. Methods. This was a single-centre, randomized, double-blind, double-dummy, two-period crossover study. Patients received V1512 (melevodopa 100 mg/carbidopa 25 mg) or L-dopa 100 mg/carbidopa 25 mg, 7 doses over 24 hours (Cohort 1), 4 doses over 12 hours (Cohort 2), or 2 doses over 12 hours in combination with entacapone 200 mg (Cohort 3). Pharmacokinetic parameters included area under the plasma-concentration time curve (AUC), maximum plasma concentration (C max), and time to C max (t max). Results. Twenty-five patients received at least one dose of study medication. L-dopa absorption tended to be quicker and pharmacokinetic parameters less variable after V1512 versus L-dopa/carbidopa, both over time and between patients. Accumulation of L-dopa in plasma was less noticeable with V1512. Carbidopa exposure and interpatient variability was lower when V1512 or L-dopa/carbidopa was given in combination with entacapone. Both treatments were well tolerated. Conclusions. V1512 provides a more reliable L-dopa pharmacokinetic profile versus standard-release L-dopa/carbidopa, with less drug accumulation and less variability. This trial is registered with ClinicalTrials.gov NCT00491998.

Patient and physician views on the quality of care in inflammatory bowel disease: results from SOLUTION-1, a prospective IG-IBD study.

INTRODUCTION: Remarkable differences in quality of care (QoC) might be observed in different countries, affecting quality of life of inflammatory bowel disease (IBD) patients. The aim of this study was to assess patient and physician perceptions of the QoC in Italy. METHODS: A multicentre observational study on the quality of care in IBD (SOLUTION-1) was conducted in 36 IG-IBD (Italian Group for Inflammatory Bowel Disease) centres in Italy. The QUOTE-IBD (Quality of Care Through the Patient's Eyes) questionnaire was administered to IBD patients and to the attending physicians. The Quality Impact (QI) score summarises the QUOTE-IBD questionnaire, and a QI >9 is considered satisfactory. RESULTS: Nine-hundred-ninety-two patients and 75 physicians completed the QUOTE-IBD questionnaire. The patients scored the domains of competence (9.47 vs. 8.55) and costs (9.54 vs. 8.26) higher that the physicians, while information (9.31 vs. 9.43) and continuity of care (8.40 vs. 9.01) were scored lower. The QI score was rated worse by physicians with less experience (<12 years) with regard to competence (8.0 vs. 9.01), courtesy (8.12 vs. 10.0) and autonomy (8.97 vs. 10.0). Physicians considered the cost domain unsatisfactory. CONCLUSIONS: Healthcare was rated as satisfactory overall for Italian patients and physicians. The physicians underestimate their competence and consider the cost of medical management unsatisfactory. The patients are more critical regarding the continuity of care and information. Country-specific data on QoC allow local governments to allocate resources more effectively.

Liquid melevodopa versus standard levodopa in patients with Parkinson disease and small intestinal bacterial overgrowth.

OBJECTIVES: Patients with Parkinson disease exhibit a highly increased prevalence of small intestinal bacterial overgrowth (SIBO), which has been also associated with the severity of motor fluctuations. Aim of this study was to test the efficacy of liquid levodopa with higher bioavailability in patients with SIBO. METHODS: Thirty-three patients with Parkinson disease underwent both lactulose and glucose breath tests to assess the presence of SIBO. A urea breath test was performed to assess the presence of a concomitant Helicobacter pylori infection. Patients were challenged with 250 mg of levodopa and 314 mg of levodopa methylester. Drug challenges were performed on different days and at baseline and 1 month after SIBO eradication. During the tests, the motor condition and the plasma levodopa concentrations were evaluated. RESULTS: At baseline, the onset of motor benefit was significantly shorter after melevodopa than after standard levodopa, as confirmed by the latency to motor on condition and t max (time to the on condition, 28.8±11.5 vs 55.5±40.2 minutes; P=0.0004; and t max, 28.2±9.7 vs 50.0±11.0 minutes; P=0.002). The duration of the on time or area under the curve was not significantly different. The underlying gastrointestinal condition did not influence these results. CONCLUSIONS: The reduction of the latency to the on condition in the absence of a reduction of the on duration is a promising feature of melevodopa because this effect would increase the total daily on duration. Future studies that evaluate the usefulness of melevodopa beyond the acute challenge (eg, using motor diaries) in patients with gastrointestinal infections are warranted.

Microscopic colitis and colorectal neoplastic lesion rate in chronic nonbloody diarrhea: a prospective, multicenter study.

BACKGROUND: Lymphocytic and collagenous colitis are emerging as common findings in subjects undergoing colonoscopy for chronic non-bloody diarrhea (CNBD). Data concerning microscopic colitis (MC) are still limited and affected by controversial epidemiological evidences. Recent converging lines of evidence suggest that MC correlates a lower risk of colorectal neoplasia. Accordingly, we prospectively assessed MC prevalence in a multicenter cohort of subjects submitted to colonoscopy for CNBD, thereby defining whether MC influences the risk of colorectal neoplasia. METHODS: Consecutive patients with CNBD of unknown origin underwent pan-colonoscopy with multiple biopsies. The prevalence of neoplastic patients in MC was compared with that observed in negative CNBD subjects. RESULTS: Among 8006 colonoscopy, 305 subjects were enrolled for CNBD. Patients with CNBD were more likely to be women than men (odds ratio = 1.5; P = 0.001). Histopathology detected high prevalence of MC (16%) with a clear predominance of collagenous colitis (70%). A striking age-dependent rise in MC-associated risk was observed, depicting outstanding differences among varying age groups, as in the number needed to screen 1 new case. Gender distribution was balanced within MC patients (Female/Male = 1.5/1), especially among lymphocytic colitis (Female/Male = 1.2/1). MC patients were negatively associated with the risk of neoplastic polyps compared with negative CNBD subjects (odds ratio = 0.22; P = 0.035). CONCLUSIONS: MC is the first cause of CNBD in subjects submitted to colonoscopy. Multiple biopsies are strongly recommended, even in the case of uneventful endoscopic inspection, especially for age ≥40 years. MC has a reduced risk of colorectal neoplasia, suggesting that this model of chronic inflammation plays a protective effect against colorectal carcinogenesis.

The role of small intestinal bacterial overgrowth in Parkinson's disease.

Parkinson's disease is associated with gastrointestinal motility abnormalities favoring the occurrence of local infections. The aim of this study was to investigate whether small intestinal bacterial overgrowth contributes to the pathophysiology of motor fluctuations. Thirty-three patients and 30 controls underwent glucose, lactulose, and urea breath tests to detect small intestinal bacterial overgrowth and Helicobacter pylori infection. Patients also underwent ultrasonography to evaluate gastric emptying. The clinical status and plasma concentration of levodopa were assessed after an acute drug challenge with a standard dose of levodopa, and motor complications were assessed by Unified Parkinson's Disease Rating Scale-IV and by 1-week diaries of motor conditions. Patients with small intestinal bacterial overgrowth were treated with rifaximin and were clinically and instrumentally reevaluated 1 and 6 months later. The prevalence of small intestinal bacterial overgrowth was significantly higher in patients than in controls (54.5% vs. 20.0%; P = .01), whereas the prevalence of Helicobacter pylori infection was not (33.3% vs. 26.7%). Compared with patients without any infection, the prevalence of unpredictable fluctuations was significantly higher in patients with both infections (8.3% vs. 87.5%; P = .008). Gastric half-emptying time was significantly longer in patients than in healthy controls but did not differ in patients based on their infective status. Compared with patients without isolated small intestinal bacterial overgrowth, patients with isolated small intestinal bacterial overgrowth had longer off time daily and more episodes of delayed-on and no-on. The eradication of small intestinal bacterial overgrowth resulted in improvement in motor fluctuations without affecting the pharmacokinetics of levodopa. The relapse rate of small intestinal bacterial overgrowth at 6 months was 43%. © 2013 Movement Disorder Society.

Glucocorticosteroids in the treatment of inflammatory bowel disease and approaches to minimizing systemic activity.

Inflammatory bowel diseases (IBDs) are a group of inflammatory conditions characterized by chronic, uncontrolled inflammation of the gastrointestinal tract. Reported prevalence is high in the United States and northern Europe, while the incidence varies greatly across the rest of Europe. Glucocorticosteroids are the standard treatment for IBD, but due to adverse events their use can be limited. However, new formulations of glucocorticosteroids have been developed to reduce systemic activation. The aim of this review was to assess and summarize the efficacy and safety of new formulations of glucocorticosteroids. A MEDLINE search identified publications focused on new formulations of nonsystemic steroid-based drugs for IBD and benefits and limitations of each of the new glucocorticosteroid formulations were identified. Budesonide has good efficacy and is an established treatment for Crohn's disease; it has been shown to be beneficial for the induction of remission in these patients, although it is not recommended for the maintenance of induced remission. Glucocorticosteroids are not recommended for the maintenance of remission in patients with IBD. However, a recent study suggested that beclomethasone dipropionate may be effective for prolonged treatment in patients in the postacute phase of Crohn's disease who were treated with a short course of systemic steroids. The efficacy of fluticasone propionate and prednisolone metasulphobenzoate in IBD is not well established given the small number of patients enrolled in the few published clinical trials. While the tolerability of these glucocorticosteroids is favourable, more research comparing these new agents with traditional systemic glucocorticosteroids is warranted.

Selegiline: a reappraisal of its role in Parkinson disease.

Selegiline at the doses used in Parkinson disease is a selective irreversible monoamine oxidase type B inhibitor, which potentiates dopaminergic function in the brain, and is used as monotherapy in early Parkinson disease or in combination with levodopa in more advanced disease. A renewed interest in monoamine oxidase type B inhibitors in the treatment of Parkinson disease has emerged after recent clinical trials of agents in this class. The use of selegiline monotherapy in early Parkinson disease is supported by the results of a large well-controlled trial in 800 patients (DATATOP) and several other studies, which demonstrated a symptomatic benefit, a reduction in disability, and a delay in the need to start levodopa therapy. Administered with levodopa in studies of up to 5 years' duration in patients with more advanced disease, selegiline improved disease-related disability, reduced the end-of-dose motor fluctuations, and also led to a reduction of the dose and dose frequency of levodopa required.Selegiline was the first drug to be investigated as a possible neuroprotective agent in patients with Parkinson disease, based on preclinical studies indicating protection of dopaminergic neurons from damage. The results of the extensive body of clinical trials, including delayed and lower levodopa requirements, may indeed suggest that selegiline, in addition to conferring symptomatic benefit, may have other effects on disease progression. Selegiline is well tolerated, and initial fears of increased mortality with the drug have not been borne out by subsequent robust meta-analyses.

Absence of mucosal inflammation in uncomplicated diverticular disease.

BACKGROUND: Uncomplicated diverticular disease is a common condition in patients older than 50 years. Symptoms are aspecific and overlapping with those of irritable bowel syndrome. Nowadays, patients are often treated with antinflammatory drugs (5-aminosalicilic acid). AIM: Our purpose was to evaluate the presence of inflammation in the colonic mucosa of patients with symptomatic uncomplicated diverticular disease compared with subjects without diverticula. METHODS: Endoscopic biopsies of colon from 10 patients with symptomatic uncomplicated diverticular disease and 10 from subjects without diverticula (controls) were taken. Specimens were homogenised and IL2, IL4, IL5, IL8, IL10, IL12p70, IL13, IFN gamma, TNF alfa (searchlight multiplex technique), TGF beta, transglutaminase type 2 and caspase 9 were measured. Histochemistry for transglutaminase type 2 and TUNEL were performed on the histological sections, in addition to morphologic evaluation, as markers of tissue remodelling and apoptosis. For statistical analysis Student's t test and Spearman correlation test were used. RESULTS: No histological differences were detected between the patients with an uncomplicated diverticular disease and controls. Mean values of mucosal cytokines and of the other tested parameters did not show statistically significant differences between patients with uncomplicated diverticular disease and controls. CONCLUSIONS: Even if based on a small number of patients, the study demonstrates the absence of inflammation in the mucosa of subjects affected by uncomplicated diverticular disease.

Beclomethasone dipropionate in Crohn's ileitis: a randomised, double-blind trial.

BACKGROUND: Steroids, the mainstay of Crohn's disease treatment, have been associated with systemic side effects. AIM: To evaluate the efficacy and tolerability of beclomethasone dipropionate for maintaining remission induced by a short course of systemic steroids in patients with Crohn's ileitis with or without right colonic involvement. METHODS: Patients (n=84) with active Crohn's disease who achieved remission during a 2-week prednisone run-in period were randomised to receive beclomethasone dipropionate for 24 weeks or continue prednisone for a further 2 weeks followed by placebo for 22 weeks. The primary outcome was relapse rate (Crohn's Disease Activity Index score>150 and an increase of ≥60 points from baseline) or withdrawal due to disease deterioration. RESULTS: The relapse rate was 23.3% and 53.8% in beclomethasone dipropionate and placebo groups, respectively (p=0.027). According to Kaplan-Meier analysis, the cumulative relapse rate was 38.0% in the beclomethasone dipropionate group and 56.0% in the placebo group (p=0.025). Six percent and 1.7% of all adverse events in the beclomethasone dipropionate and placebo groups, respectively, were endocrine-related. CONCLUSION: These results demonstrate that beclomethasone dipropionate significantly reduces the relapse rate in post-active Crohn's ileitis patients compared with placebo after induction of remission with a short course of systemic steroids, and is well tolerated.

Factors associated with motor fluctuations and dyskinesia in Parkinson Disease: potential role of a new melevodopa plus carbidopa formulation (Sirio).

Parkinson disease is a progressive movement disorder caused by loss of dopaminergic neurons in the substantia nigra. Of unknown etiology, Parkinson disease is characterized by 4 cardinal symptoms: tremor at rest, bradykinesia, postural instability, and rigidity. The current criterion-standard drug used in the management of parkinsonian symptoms is levodopa (l-dopa). However, long-term l-dopa therapy is associated with the development of motor complications; approximately 50% to 80% of patients will develop motor complications within 5 to 10 years of l-dopa treatment initiation. Motor complications can be divided into motor fluctuations, caused largely through pulsatile dopamine stimulation and low l-dopa concentrations, and dyskinesia, associated more often with peak l-dopa concentrations. Ultimately, the main goal was to provide steady l-dopa concentrations, without peaks and troughs. Empirical investigations using parenteral infusions of l-dopa and highly soluble l-dopa prodrugs have shown that there is benefit in ameliorating the peaks and troughs associated with traditional oral l-dopa formulations. Recently, the development of highly soluble oral l-dopa prodrugs has facilitated rapid, regular, and reliable l-dopa availability. This review evaluates some of the pharmacologic strategies in the management of motor complications in Parkinson disease and therapy optimization, with a focus on the use of CHF 1512 (Sirio), a combination of melevodopa (l-dopa methylester, a highly soluble prodrug of l-dopa) plus carbidopa in an effervescent tablet formulation.

Oral beclomethasone: a review of its use in inflammatory bowel disease.

Corticosteroids have represented the mainstay of medical treatment for induction of remission in inflammatory bowel disease. Aim of this paper is to review mechanisms of action, safety and efficacy of beclomethasone dipropionate, a steroid with enhanced topical intestinal activity and low systemic activity, in the treatment of inflammatory bowel disease.

Short-term continuous infusion of apomorphine hydrochloride for treatment of Huntington's chorea: A double blind, randomized cross-over trial.

We evaluated tolerability and the efficacy of continuous infusion of apomorphine hydrochloride on involuntary movements and mood disorder in Huntington's disease (HD) patients in a pilot, single center, double-blind, randomized, crossover, and controlled versus placebo study. Nine patients with a molecular diagnosis of HD were screened for response to acute apomorphine injection. Four of them, not ameliorating at the acute test, were discontinued. Five patients, responding to acute apomorphine, received continuous infusion of either apomorphine or placebo for 5 days. After 2 days of washout, the alternative treatment was administered. Primary endpoint measures were scores of the Unified Huntington's Disease Rating Scale (UHDRS "motor section") and of the Abnormal Involuntary Movement Scale (AIMS). Secondary endpoint measures were the Hamilton Depression Rating Scale (HAD) score and safety parameters. Both UHDRS and AIMS scores significantly decreased in all patients after apomorphine. The beneficial effect of apomorphine was recorded throughout the 5 treatment days. The HAD score did not change after infusion of either treatment. No serious adverse events were reported by either group during the study. Our results suggest that continuous infusion of apomorphine might be considered for the treatment of involuntary movements in some HD patients.

Chelation therapy and bone metabolism markers in thalassemia major.

The aim of our study was to investigate the effects of subcutaneous desferrioxamine (DFX) and oral deferiprone (L1) therapy on bone metabolism markers in patients with thalassemia major. We studied 17 patients with thalassemia receiving long-term treatment with desferrioxamine, 20 patients receiving long-term treatment with deferiprone, and 15 healthy age-matched controls. The following investigations were performed: a) intact parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D] as endocrine parameters; b) alkaline phosphatase (ALP), bone alkaline phosphatase (BALP), osteocalcin (OC); c) bone resorption biochemical markers in serum and urine pyridinium crosslinks: hydroxylysyl-pyridinoline (HP) and lysyl-pyridinoline (LP); d) serum levels of cytokines and growth factors: transforming growth factor-beta1 (TGFbeta1), insulin-like growth factor-I (IGF-I), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-a (TNFalpha); e) serum levels of IGF binding protein-3 (IGFBP-3). No significant differences among all studied variables were found in patients with thalassemia treated with desferrioxamine or deferiprone. In contrast, significant differences were found between patients with thalassemia and the control group: intact PTH was significantly lower in patients with thalassemia than in the controls (p < 0.0005), and a significant increase in ALP and BALP (p < 0.0005), but not in OC, was found in the patient group. With regard to bone resorption and remodeling markers, the urinary excretion of pyridinium crosslinks was higher in patients with thalassemia for HP fraction (p < 0.0005) and LP fraction (p = 0.002), as well as TGFbeta (p = 0.001). In contrast, IGF-I and IGFBP-3 were reduced when compared with controls. In conclusion, the study of bone metabolism markers in adult patients with thalassemia reveals a complex behavior with an increase in bone resorption indexes. Bone formation did not appear to be impaired. In particular, TGFbeta1 was higher in patients with thalassemia receiving L1 treatment.

[Cost analysis in Italy of various strategies for the treatment of Parkinson disease in the advanced phase]. / Analisi dei costi, in Italia, di diverse strategie per il trattamento della malattia di Parkinson in fase avanzata.

OBJECTIVE: To perform a comparative economic evaluation of therapies--L-dopa drugs, subcutaneous infusion of apomorphine and surgical intervention of Deep Brain Stimulation (DBS)--for the treatment of advanced Parkinson's disease (APD) and to verify the level of assistance guaranteed in Italy to patients affected by APD. METHODS: Literature review and Delphi Panel to collect data about the efficacy of the therapies for the treatment of APD and the use of healthcare resources for such therapies. Field survey to investigate financing mechanisms of the therapeutical alternatives in the Italian regions; cost-analysis over five years (NHS perspective); cost-analysis (hospital perspective) for the initial administration of therapeutic alternatives. RESULTS: Literature review shows that the reduction of the "off-periods" is 62% for Apomorphine and 80-90% for DBS compared to traditional therapy. The 5-years economic analysis from the NHS perspective shows that the cost of a patients with APD is [symbol: see text] 58.065 if treated with traditional therapy, [symbol: see text] 36.423 (including infusional pump and the drug) with subcutaneous apomorphine and respectively [symbol: see text] 56.489 and [symbol: see text] 41.379 (depending on reimbursement of electrodes and neurostimulator on top of the DRG tariff) with DBS. The field survey, highlighted that Regions which currently reimburse the infusion pump for apomorphine and the electrodes and neurostimulator for DBS--on top of the DRG tariff--are a very limited number. CONCLUSIONS: Apomorphine and DBS in the treatment of APD show higher efficacy and lower costs compared to traditional therapy.