Low glomerular filtration rate is a risk factor for ribavirin-associated anaemia in old patients with chronic hepatitis C.

Elderly patients with chronic hepatitis C have a reduced responsiveness to antiviral therapy with Peg-interferon and ribavirin. The dose reduction or the discontinuation of ribavirin due to the occurrence of anaemia is one of the most important causes for the low sustained viral response observed in older patients. We aimed to evaluate the relationship between baseline renal function and the early onset of ribavirin-associated anaemia in older (≥60 years) patients. Using data from 348 patients with chronic hepatitis C consecutively treated with peg-interferon plus ribavirin, we investigated which factors were associated with the occurrence of anaemia in elderly patients (≥60 years). Ribavirin-induced anaemia occurred in 40.5% of patients. Older patients showed a rate of anaemia significantly higher than younger patients (51.5% vs 36.3%; P = 0.009). Consequently, the rate of ribavirin dose reduction or discontinuation due to anaemia was 35.1% in older patients and 23.5% in younger patients (P = 0.029). A significantly higher proportion of older patients had a low baseline glomerular filtration rate (GFR) compared with younger patients (56.7% vs 27.1%; P < 0.001). At the multivariate regression analysis, low baseline GFR (<70 mL/min) was associated with an increased risk of ribavirin-associated anaemia only in the older patients (OR: 3.526; 95% CI: 1.385-8.979; P = 0.008). In this subset, baseline GFR was significantly correlated with both absolute (r = -0.320; P < 0.001) and relative (r = -0.324; P < 0.001) haemoglobin decrease within the first 8 weeks of treatment. In patients aged >60 years, a low pre-treatment GFR was strongly associated with the risk to develop ribavirin-related anaemia with consequent reduction in ribavirin doses.

Effectiveness of pegylated interferon/ribavirin combination in 'real world' patients with chronic hepatitis C virus infection.

BACKGROUND: Clinical trials have shown that the combination of pegylated interferon/ribavirin induces a sustained virological response in 54-63% of patients with chronic hepatitis C virus infection, but its effectiveness in day-to-day clinical practice is less clear. AIM: To verify if the efficacy of pegylated interferon/ribavirin combination in 'real world' patients is comparable to that observed in trials. Methods The medical records of 397 consecutive naïve patients with chronic hepatitis C virus infection treated with pegylated interferon/ribavirin combination in nontertiary hospital settings were reviewed in order to assess the response to anti-viral treatment. RESULTS: The sustained virological response rate achieved in this population was similar to that recorded in registration trials (total population: 64%; genotype 1: 46%; genotypes 2-3: 84%). Also, the premature discontinuation rate (15%) was similar to that observed in registration trials, but there were fewer dose reductions in one or both medications (26%). We confirmed the association between adherence and sustained virological response among the patients infected with hepatitis C virus genotype 1 who were treated for > or =80% of the planned duration of treatment. CONCLUSION: The effectiveness of pegylated interferon/ribavirin therapy and factors predicting an sustained virological response in everyday clinical practice mirror those reported in randomized-controlled studies.

[Treatment of acute inflammatory pathology of the upper airway with morniflumate]. / Trattamento delle patologie infiammatorie acute delle vie aeree superiori con morniflumato.

Sixty patients, 33 men and 27 women (mean age about 45 years; range 25-60), affected by acute influenza syndrome of the upper airways were admitted to a controlled single-blind study with three drugs under parallel conditions. According to a balanced randomized sequence, the subjects were treated over a 7-10 day period with morniflumate sachets (700 mg bid) or with tiaprofenic acid sachets (300 mg bid) or with paracetamol (10 ml syrup equivalent to 500 mg tid). The efficacy of the test drugs was assessed by determining the local and general signs and symptoms before starting the treatments, in basal conditions, and on the 3rd, 5th and last day of treatment. At the doses and formulations used, morniflumate proved to be equivalent to paracetamol and more effective than tiaprofenic acid as for its antipyretic action in the first days of treatment. On the other hand, both morniflumate and tiaprofenic acid showed a significantly higher antiinflammatory effect compared to paracetamol. Pain was effectively and equally controlled in all the treatment groups. The drugs administered were generally well tolerated. A greater incidence of adverse GI events was reported in the group treated with tiaprofenic acid.

[Efficacy and tolerability of paracetamol-sobrerol combination in patients with hyperpyrexia]. / Efficacia e tollerabilità dell'associazione paracetamolo-sobrerolo nel paziente iperpiretico.

The therapeutic efficacy and tolerability of the association paracetamol-sobrerol in comparison with paracetamol alone, was tested in a double-blind, randomized clinical trial, carried out on 287 out-patients, suffering from diseases of the respiratory tree with fever. The treatment was performed for up to five days. At the end of the treatment, both treatments lead to an important improvement of all considered clinical parameters; furthermore, the association paracetamol-sobrerol showed a statistically important difference versus paracetamol alone as to cough and difficulty to expectorate. As to body temperature, both paracetamol and paracetamol-sobrerol showed a good antipyretic activity; furthermore, the association compared to paracetamol alone obtained a statistically significant differences in times x treatments. These data fully confirm the results obtained from recent studies: the simultaneous administration of paracetamol and sobrerol obtains a better antipyretic action than paracetamol alone. This synergism allows to reduce paracetamol doses and, consequently, to eliminate the already low incidence of adverse reactions, without decreasing the antipyretic activity.

Effects of erdosteine on sputum biochemical and rheologic properties: pharmacokinetics in chronic obstructive lung disease.

Erdosteine is a new thioderivative endowed with mucokinetic, mucolytic, and free-radical-scavenging properties. This study evaluated (in a double-blind design vs. placebo) its efficacy on biochemical and rheologic properties of sputum and on some indices of respiratory function in chronic patients with chronic bronchitis (10 per group), while receiving basic treatment with a controlled-release theophylline preparation. The pharmacokinetics of erdosteine and theophylline were also studied. We found that a 2 week treatment with erdosteine (300 mg 3 times daily) was able to reduce significantly (p less than 0.05) the sputum apparent viscosity, fucose content, and macromolecular dry weight (MDW) with no statistically significant influence on sputum elasticity, DNA, albumin, total proteins, total IgA, lactoferrin, and lysozyme content. The treatment caused a significant increase in the following ratios: total IgA/albumin, lactoferrin/albumin, and lysozyme/albumin. The pharmacokinetics of erdosteine, its metabolites, and theophylline were the same after 1 or 14 days of treatment, evidence both of absence of an enzymatic induction and of an accumulation process. Further confirmation that there was no interference between erdosteine and theophylline was obtained from the data available on the group of patients receiving only theophylline, since its plasma levels and related pharmacokinetic parameters were identical to those obtained in patients receiving both drugs. In conclusion, 2 weeks of therapy with erdosteine reduced the marker of mucus glycoproteins (fucose) in patients with chronic bronchitis but did not interfere with the pharmacokinetics of xanthine derivatives. We also suggest that the significant increment in the IgA/albumin ratio might be related to a sum of other local effects such as reduction of the inflammatory process and enhancement of the humoral defense mechanism.

[Enoxacin in the treatment of bacterial infections of the respiratory system]. / L'enoxacina nel trattamento di infezioni batteriche a carico dell'apparato respiratorio.

The above study was carried out in 30 patients, 22 males, 8 females, aged between 30 and 66 years, average age 57.17 +/- 1.43 years, 19 of whom with flare-ups of chronic or asthmatic bronchitis, 6 suffering from flare-ups of chronic bronchoectasic bronchitis, and 5 with acute tracheobronchitis. Treatment with two 300 mg tablets of enoxacin daily lasted from 10 to 15 days. The clinical result was good in 95% of the cases, and microbiological results were also satisfactory in that the micro-organisms isolated were sensitive to the antibiotic. Tolerance was good both locally and generally, only two patients complained of slight stomach discomfort. Both symptoms and laboratory findings improved progressively, and the result was considered excellent in four cases, good in 25 and only fair in one.

Clinical study on bronchodilation induced by a metered aerosol of fenoterol in combination with ipratropium bromide.

The response to an aerosol preparation containing 100 micrograms fenoterol and 40 micrograms ipratropium bromide per puff (Duovent) was compared with a placebo in 18 asthmatic patients in a double-blind cross-over fashion. We measured changes in lung function tests and pulse rate. Duovent induced a significant improvement in lung tests with statistical relevance for VEMS and Raw in comparison with placebo. The combination of fenoterol and ipratropium bromide also provided a long-lasting bronchodilatation without side effects.