Observational study to evaluate the impact of internet reminders for GPs on colorectal cancer screening uptake in Northern Italy in 2013.

INTRODUCTION: Colorectal cancer (CRC) is the third most common cancer worldwide and CRC-related mortality can be effectively reduced by population-based screening. Screening uptake is a key indicator of performance, susceptible of several implementation methods. Participation in ASL Milano 1 area (northern Italy) is increasing thanks to reminder invitation sent to non-responders. Here we evaluate the implementation of another strategy among those proved to be effective. METHODS: In the years 2013-2014 we conducted an observational study in patients non-responder to first invitation and subsequent mailed reminder. A list of them was sent to their own GP, who had the task to evaluate possible exclusion criteria and make a reminder, either by personal interview, telephone call or via e-mail. Intervention could be conducted either by the GP himself or by an assistant. Primary outcomes were to assess the overall efficacy of the intervention and the efficacy of its single features (type of intervention and provider), measuring the consequent uptake of CRC screening. RESULTS: Participation in CRC screening was significantly higher (33,5%) in patients who received a reminder from GP, regardless of the type, vs those who did not (19,0%, p < 0.01). No statistically significant difference was detected either by method or by provider of the intervention. DISCUSSION: The results of our study demonstrate that even a modest intervention can have a significant effect in improving compliance to screening for CRC, one of the cancers with highest incidence in developed countries, for which an effective treatment is available in case of early diagnosis.

Paediatric upper respiratory infections: the role of antibiotics.

To review current clinical evidence for the use of antibiotics in paediatric upper paediatric respiratory infections, repeated PubMed searches using the template algorithm -rhinosinusitis/otitis/ tonsillitis AND ()- with the settings: -Humans; English; All Child 0-18; Clinical trial; Review; Methanalysis; Guideline; Last 10 years- for the following comparators: antibiotic; amoxicillin; clavulanate; penicillin; cephalosporin; macrolide; erythromycin; rokitamycin; clindamycin; trimethoprim-sulfamethoxazole, cefopodoxime, cefdinir, cefuroxime, ceftriaxone. The authors clinical experience in the paediatric allergy unit of a University hospital was also drawn upon. A narrative review was drafted to update paediatricians on the topic. Many paediatric studies and guidelines were retrieved satisfying current evidence-based medicine standards. There are stringent indications for antibiotic use in URTIs. The paediatric use is widespread raising doubts on their appropriate prescription in many countries. Evidence for the efficacy of antibiotic treatment for paediatric URTIs is available and this treatment should be included in individualised patient protocols on the basis of the clinical literature. Caution must be posed at the local level taking in account epidemiologic and microbiologic data to avoid overprescription.

[Clarithromycin switch therapy in adult patients suffering from community-acquired lower respiratory tract infections (LRTIs) requiring hospitalisation]. / La terapia sequenziale (switch-therapy) con claritromicina nelle infezioni delle basse vie respiratorie acquisite in comunita' che richiedono ospedalizzazione.

39 subjects aged 53-85 years suffering from COPD, admitted to our Unit, were enrolled in our study: four patients were diagnosed as having CAP; 35 patients meet the criteria of COPD exacerbation. The enrolled patients had been receiving clarithromycin (CLA) 500 mg i.v. every 12 hours; switching to oral therapy was decided on the basis of Ramirez's criteria. The mean total duration (SD) of treatment with CLA was 9.56 (1.87) days. During the study, 2 patients dropped out because of the detection of malignant tumoral cells in the sputum in one case and admission to the Intensive Care Unit because of pulmonary thromboembolism in the other. The clinical assessment made 24-72 hours after the end of the treatment confirmed the clinical efficacy of CLA (cure + improvement) in 35 out of 37 evaluable patients (94.59%). At the first follow-up visit, clinical efficacy was confirmed in 34 patients (91.89%). At the long-term follow-up visit, performed 30-45 days after the end of the study, none of the 34 "cured" patients had relapsed. Local and systemic tolerability was excellent in all patients, and no side effect attributable to the drug was reported. Our experience with switched clarithromycin therapy in patients with LRTIs confirms the validity of this approach.

[Treatment of Community Acquired Pneumonia (CAP) in adults with amoxicillin/clavulanic acid switch therapy: a multicenter italian study] / Trattamento della polmonite acquisita in comunita' nell'adulto, dopo fallimento dl terapia antibiotica orale domiciliare, con amoxicillina/acido clavulanico switch therapy. Esperienza italiana.

Patients with community acquired pneumonia (CAP) previously treated with other oral antibiotics (Cephalosporins 35,3%, Macrolides 26,9%, Tetracyclines 14,1%, Quinolones 12,8%, other 10,9%) for at least 72 hours at home were considered for this national multicentre study. 43 hospitalized patients (17 males and 26 females) ranging between the ages of 19 and 79 were treated with Amoxicillin/Clavulanic acid (AMC) 1,2 g e.v., T.l.D. for at least 3 days. I.V. Treatments were switched to AMC p.o. after apyrexial status. Average treatment duration was 10,8 + 3.6. Sputum/B.A.L. samples were obtained from all patients submitted for microbiological exams in order to determine microbiological aetiology of CAP in patients who have failed on previous antibiotics. At the end of treatment, 30 patients (96,8%) were considered cured, while treatment failed in 1 patient (3,2%). 12 patients were considered not evaluable because serology was positive for M.pneumoniae (5 pts); for C.pneumoniae (3 pts.); 1 patients was positive for Mycobacterium tuberculosis; 1 patient was positive for HIV and Mycobacterium spp.; 2 patients were non-evaluable for lung or bronchial tumor. Not reported adverse events.

Comparative evaluation of the clinical and microbiological efficacy of co-amoxiclav vs cefixime or ciprofloxacin in bacterial exacerbation of chronic bronchitis.

In an open randomized study 218 outpatients (159 males and 59 females) ranging between 18 and 85 years of age (mean 61.9) suffering from bacterial exacerbation of chronic bronchitis have been randomly treated: 79 with co-amoxiclav (amoxicillin 875 mg+clavulanic acid 125 mg) twice daily, 69 with cefixime (400 mg) once daily, and 70 with ciprofloxacin (500 mg) twice daily for an average period of 10 days. Before treatment start, 234 bacterial strains (105 Gram-positive and 129 Gram-negative) were isolated as the cause of exacerbation; the leading pathogens were Streptococcus pneumoniae and Haemophilus spp. Eradication rates at the end of treatment were 82.2% for the co-amoxiclav group, 77.6% for the cefixime group, and 81.2% for ciprofloxacin group. Clinical success (cure+improvement) was obtained in 90.8% of the cases treated with co-amoxiclav, in 80.9% for the cefixime group and in 85.7% of patients treated with ciprofloxacin. Seven adverse events (8.9%) of which 4 cases of diarrhea and 3 of itching, were recorded in the co-amoxiclav group. Eleven adverse events (14.7%) were recorded in the cefixime group including gastrointestinal disturbances in 6 patients and mild to moderate increase of liver function in 2. Nine adverse events (12.9%) occurred in the ciprofloxacin group, including insomnia in 3 patients, gastrointestinal disturbances in 2, and serious increase of liver function tests in one patient. It can be concluded that there were no statistically significant differences among the three treatment groups. However, co-amoxiclav demonstrated a higher efficacy rate than cefixime and ciprofloxacin and was better tolerated. Therefore, it can be used as a first-choice drug in the treatment of exacerbation of chronic bronchitis.

Efficacy and tolerability of azithromycin versus amoxicillin/clavulanic acid in acute purulent exacerbation of chronic bronchitis.

An open randomized trial was conducted in 142 hospitalized and out-patients with acute purulent exacerbation of chronic bronchitis to compare the clinical efficacy and tolerability of azithromycin (n = 69) and amoxicillin/clavulanic acid (n = 73). Azithromycin (500 mg) was administered as a single dose for three days and amoxicillin/clavulanic acid (amoxicillin 875 mg-clavulanic acid 125 mg) was given b.i.d. for 8 days (8.16 +/- 1.18). Before therapy and 24-48 hours after the end of treatment, sputum culture (by positioning five orthodontal swabs at the opening of salivary gland ducts after a washing of the oral cavity with sterile saline solution to avoid oral contamination), chest X-rays, arterial blood gas analysis, trials of respiratory functions and routine blood tests were performed. In the azithromycin group (69 patients) the efficacy rate was 67.6% (46 patients: 34 cured and 12 improved); in 22 patients (32.4%) the treatment failed; 1 patient was not evaluated because of no follow-up. The overall efficacy rate in the amoxicillin/clavulanic acid group (73 patients) was 97.3% (71 patients: 60 cured and 11 improved); in 1 patient (1.4%) the treatment failed and 1 patient was a drop-out for side effects. All pathogens isolated before treatment were susceptible to the antibiotics administered. At the end of treatment microbiological efficacy was 67.1% in the azithromycin group and 98.6% in the amoxicillin/clavulanic acid group. The tolerability was judged good in both treatment groups. Side effects were observed in 1 patient treated with amoxicillin/clavulanic acid (diarrhea), which imposed interruption of treatment, and in 2 patients from the azithromycin group (gastralgia and biochemical laboratory tests: renal function).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative clinical and microbiological study of amoxycillin-clavulanic acid and ciprofloxacin in acute purulent exacerbations of chronic bronchitis.

In a retrospective study, the clinical and microbiological efficacy of amoxycillin-clavulanic acid and ciprofloxacin were evaluated in outpatients observed within the previous year who were affected by acute purulent exacerbations of chronic bronchitis. Of the 95 patients included in the trial, 50 received amoxycillin 875 mg-clavulanic acid 125 mg 8-hourly for 10 days and 45 received ciprofloxacin 500 mg 12-hourly before meals for 10 days. Of the amoxycillin-clavulanic acid-treated patients, 90% showed clear clinical improvement and in 10% treatment failed. In the ciprofloxacin group, 75.5% of patients showed improvement and in 24.5% treatment failed. All pathogens isolated prior to therapy were susceptible to the antibiotic used for therapy. At the end of treatment, in the amoxycillin-clavulanic acid-treated group, 84% of strains were eradicated and 8% persisted; others were superinfections. In the ciprofloxacin group, 57.7% of strains were eradicated, 26.6% persisted and 15.5% were superinfections. No clinically significant side effects were observed in either group. Overall, amoxycillin-clavulanic acid demonstrated superior clinical and microbiological efficacy to ciprofloxacin, although this might be attributable to the higher proportion of aerobic Gram-negative pathogens in the ciprofloxacin group.

The influence of seaprose on erythromycin penetration into bronchial mucus in bronchopulmonary infections.

In bronchopulmonary infections antibiotics can be combined with other drugs, called mucoactive drugs, that act to reduce the abnormal viscoelasticity of the mucus enabling a deeper penetration of more antibiotic into the mucus. Seaprose is a protease that interacts with the polymeric fibrillar structure of the bronchial mucus to shorten the long chains of mucoproteins, DNA and other macromolecules, thus reducing the viscosity of the mucus. In order to assess whether the combination of seaprose (60 mg/8 h) plus erythromycin (500 mg/8 h) allows higher antibiotic levels in sputum than erythromycin (500 mg/8 h) plus placebo, the pharmacokinetic behaviour in sputum and in blood of these two treatments was investigated in a double-blind study in two groups of twenty patients each with bronchopulmonary infections. Serum and sputum levels were determined for each patient at the first and seventh day of the two drug regimens. Statistically significant differences for peak, AUC and MRT, were observed for erythromycin between the first and last dose in the group of patients treated with seaprose plus erythromycin; moreover significant differences for these parameters were observed between the two groups. These findings indicate the presence of a pharmacokinetic synergism between seaprose and erythromycin which allows erythromycin to penetrate bronchial secretion more easily and in higher amounts, performing a sterilizing action with therapeutic advantages.

In vitro rheological assessment of mucolytic activity induced by seaprose.

Proteolytic enzymes can act on the polymeric structure of the bronchial mucus, shortening the long chain of mucoproteins, DNA and other macromolecules, and thus reducing the viscosity of the mucus facilitating its expectoration. Seaprose (Flaminase, Puropharma) belongs to this class and is a proteinase from Aspergillus melleus and it is mainly used in traumatology, orthopaedics, gynaecology and pneumology. In the present study the in vitro activity of increasing concentrations (0.25, 0.5, 1%) of seaprose incubated with bronchial mucus samples (1 ml) was investigated by a rheological technique (transient test) that assesses changes in viscosity and elasticity. A dose-effect relationship between increasing concentrations of seaprose and the corresponding reductions in bronchial mucus viscosity was found. There was also a parallel reduction in elasticity after incubation with 0.5%, but an unfortunate distribution of values for 0.25 and 1% concentrations does not allow us to state whether there is a dose-effect relationship for elasticity.

Topical tolerability of salmon calcitonin assessed by mucociliary transport velocity investigation.

The topical tolerability of an intranasal salmon calcitonin spray preparation, of the excipients alone and of sodium taurocholate has been studied by assessment of the mucociliary transport velocity (MTV) on the frog's palate. The rate of mucus transport was investigated in 3 groups of animals (Rana esculenta; 6 frogs per group) in basal conditions and after a challenge with a salmon calcitonin intranasal spray preparation, with the excipients and with sodium taurocholate, respectively. The salmon calcitonin intranasal spray preparation and the excipients did not affect the mucociliary transport velocity on the frog's palate. On the contrary, sodium taurocholate produced severe impairments in the mucociliary transport velocity and histological lesions of the epithelial layer of the frog's palate. The comparison among the mean values of the mucociliary transport velocity before and after treatments showed a significant difference between controls and sodium taurocholate groups (p less than 0.05) as well as among the groups treated with sodium taurocholate versus salmon calcitonin and versus the excipients alone of the calcitonin preparation (p less than 0.05). These findings provide evidence that the salmon calcitonin intranasal spray preparation tested in the present ex vivo model does not affect the mucociliary transport velocity in the frog's palate, while this is markedly affected by sodium taurocholate. The use of sodium taurocholate as a promoter of absorption in intranasal preparations should thus be reconsidered.

Long-lasting effects on rheology and clearance of bronchial mucus after short-term administration of high doses of carbocysteine-lysine to patients with chronic bronchitis.

The rheological behavior and clearance of bronchial mucus samples collected by protected expectoration from 24 out-patients with simple chronic bronchitis were investigated before, at the end of a short period of treatment (4 days) with a single oral dose of 2.7 g (sachet) of carbocysteine-lysine (evening meal), and on the 4th and 8th days after the end of treatment versus placebo. In the group treated with carbocysteine-lysine, there were significant reductions in viscosity (-67, -48, -62%) and increases in mucociliary transport (+41, +31, +34%) at the three times mentioned. The most striking finding was that the improvements were still present 8 days after cessation of treatment. The elasticity parameter was not affected in any statistically significant way (-10, -24, +65%). These findings suggest the presence of some type of 'post-mucoactive' effect.

Rheological profile of nesosteine: a new mucoactive agent.

Nesosteine, a new agent shown to improve physical characteristics of bronchial mucus in animal models, has been studied in chronic bronchitic patients to confirm its effect on viscoelasticity of bronchial secretions. Sputum was collected from hypersecretory bronchitic patients in a stable condition before and after seven days of treatment with nesosteine (900 mg/day) or a placebo. At the end of treatment a significant (p less than 0.05) decrease was found in the viscosity in the nesosteine group: on the contrary, a slight, non-significant increase in viscosity was observed in the mucus samples of the placebo group. The improvement in rheological characteristics of the bronchial mucus in the patients treated with nesosteine was associated with an increase in mucus transport rate (mucociliary clearance) observed in the same samples. The findings indicate that nesosteine reduces mucus viscosity in chronic bronchitic patients and that this change induces also an improvement in mucociliary clearance.