Antonella Zambon

Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: randomised, double-blind controlled study.

BACKGROUND Intervention to achieve alcohol abstinence represents the most effective treatment for alcohol-dependent patients with liver cirrhosis; however, anticraving drugs might worsen liver disease. We aimed to investigate the effectiveness and safety of baclofen in achieving and maintaining alcohol abstinence in patients with liver cirrhosis. METHODS Between October, 2003, and November, 2006, 148 alcohol-dependent patients with liver cirrhosis were referred to the Institute of Internal Medicine, Rome, Italy. 84 were randomly allocated either oral baclofen or placebo for 12 weeks. Primary outcome was proportion of patients achieving and maintaining alcohol abstinence. Measures of this outcome were total alcohol abstinence and cumulative abstinence duration, which were assessed at outpatient visits. Relapse was defined as alcohol intake of more than four drinks per day or overall consumption of 14 or more drinks per week over a period of at least 4 weeks. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00525252. FINDINGS Of 42 patients allocated baclofen, 30 (71%) achieved and maintained abstinence compared with 12 (29%) of 42 assigned placebo (odds ratio 6.3 [95% CI 2.4-16.1]; p=0.0001). The number of dropouts (termination of treatment) did not differ between the baclofen (6/42 [14%]) and placebo (13/42 [31%]) groups (p=0.12). Cumulative abstinence duration was about twofold higher in patients allocated baclofen than in those assigned placebo (mean 62.8 [SE 5.4] vs 30.8 [5.5] days; p=0.001). No hepatic side-effects were recorded. INTERPRETATION Baclofen is effective at promoting alcohol abstinence in alcohol-dependent patients with liver cirrhosis. The drug is well tolerated and could have an important role in treatment of these individuals.

Discontinuation of and changes in drug therapy for hypertension among newly-treated patients: a population-based study in Italy.

Objectives To assess rates and determinants of treatment discontinuation of or changes in initial antihypertensive drug therapy in a large cohort of patients from Lombardia (Italy). Methods The cohort included 445 356 patients aged 40 –80 years who received their first antihypertensive drug prescription (monotherapy) during 1999–2002. Discontinuation was defined by the absence of any antihypertensive prescription during a 90-day period following the end of the latest prescription. If during the same period a drug of a different class was added or replaced the initial prescription, treatment modification was regarded as combination or switching, respectively. Competing risks methodology was used to estimate and compare cause-specific cumulative incidence. Results Cumulative incidences of discontinuation, combination and switching were respectively 33, 14 and 15% at 6 months, 41, 18 and 17% at 1 year, and 50, 25 and 19% at 5 years since initial treatment. Compared with patients starting treatment with angiotensin-converting enzyme inhibitors, the rate of discontinuation was less for patients on angiotensin receptor blockers with a hazard ratio of 0.92 (95% confidence interval =0.90-0.94), whereas increased discontinuation was observed for patients starting with other drugs, mainly β-blockers with a hazard ratio of 1.64 (1.62-1.67); and diuretics with a hazard ratio of 1.83 (1.81-1.85). Conclusion In the general population of Lombardia, discontinuation of the initial single antihypertensive drug treatment is a common phenomenon, whereas switching to another monotherapy and to combination treatment occur at similarly much lower rates. Blockers of the renin-angiotensin system are associated with the lowest incidence of treatment discontinuation.

Better compliance to antihypertensive medications reduces cardiovascular risk

Objective The effect of compliance with antihypertensive medications on the risk of cardiovascular outcomes in a population without a known history of cardiovascular disease has been addressed by a large population-based prospective, cohort study carried out by linking Italian administrative databases. Methods The cohort of 242 594 patients aged 18 years or older, residents in the Italian Lombardy Region, who were newly treated for hypertension during 2000–2001, was followed from index prescription until 2007. During this period patients who experienced a hospitalization for coronary or cerebrovascular disease were identified (outcome). Exposure to antihypertensive drugs from index prescription until the date of hospitalization or censoring was assessed. Proportional hazards models were fitted to assess the association between persistence on and adherence with antihypertensive drug therapy and outcome. Data were adjusted for several covariates. Results During an average follow-up of 6 years, 12 016 members of the cohort experienced the outcome. Compared with patients who experienced at least one episode of treatment discontinuation, those who continued treatment had a 37% reduced risk of cardiovascular outcomes (95% confidence interval 34–40%). Compared with patients who had very low drug coverage (proportion of days covered ≤25%), those at intermediate (from 51 to 75%) and high coverage (>75%) had risk reductions of 20% (16–24%) and 25% (20–29%), respectively. Similar effects were observed when coronary and cerebrovascular events were considered separately. Conclusions In the real life setting, fulfillment compliance with antihypertensive medications is effective in the primary prevention of cardiovascular outcomes.

Coffee, caffeine, and the risk of liver cirrhosis

PURPOSE To evaluate the effect of the consumption of caffeine-containing beverages on the risk of symptomatic liver cirrhosis (LC). METHODS From 1994 to 1998, all the consecutive cirrhotic inpatients admitted in 19 collaborative hospitals for signs of liver decompensation in whom the diagnosis of liver cirrhosis was made for the first time (274 cases) and one or two gender, age, and place of residence pair matched individuals (458 controls) were recruited. Data on years of education, lifetime cigarette use, lifetime intake of alcohol- and caffeine-containing beverages, usual consumption of 180 food items, and on markers of hepatitis B and C viral infection were collected. RESULTS A statistically significant trend toward lowered cirrhosis risk with increasing exposure to coffee was observed. The LC odds ratios decreased from 1.0 (reference category: lifetime abstainers from coffee) to 0.47 (95% confidence interval: 0.20, 1.10), 0.23 (0.10, 0.53), 0.21 (0.06, 0.74), and 0.16 (0.05, 0.50) in 1, 2, 3, and 4 or more cups of coffee drinkers, respectively. There was no convincing evidence that coffee consumption modifies the effects of the known risk factors of liver cirrhosis (alcohol intake and viruses infection). CONCLUSIONS These findings support the hypothesis that coffee, but not other beverages containing caffeine, may inhibit the onset of alcoholic and nonalcoholic liver cirrhosis.

Cardiovascular Protection by Initial and Subsequent Combination of Antihypertensive Drugs in Daily Life Practice

Guidelines recommend a combination of 2 drugs to be used as first-step treatment strategy in high-risk hypertensive individuals to achieve timely blood pressure control and avoid early events. The evidence that this is associated with cardiovascular (CV) benefits compared with initial monotherapy is limited, however. The objective of this study was to assess whether, compared with antihypertensive monotherapy, a combination of antihypertensive drugs provides a greater CV protection in daily clinical practice. A population-based, nested case-control study was carried out by including the cohort of 209 650 patients from Lombardy (Italy) aged 40 to 79 years who were newly treated with antihypertensive drugs between 2000 and 2001. Cases were the 10 688 patients who experienced a hospitalization for CV disease from initial prescription until 2007. Three controls were randomly selected for each case. Logistic regression was used to model the CV risk associated with starting on and/or continuing with combination therapy. A Monte-Carlo sensitivity analysis was performed to account for unmeasured confounders. Patients starting on combination therapy had an 11% CV risk reduction with respect to those starting on monotherapy (95% CI: 5% to 16%). Compared with patients who maintained monotherapy also during follow-up, those who started on combination therapy and kept it along the entire period of observation had 26% reduction of CV risk (95% CI: 15% to 35%). In daily life practice, a combination of antihypertensive drugs is associated with a great reduction of CV risk. The indication for using combination of blood pressure drugs should be broadened.

Cancer Risk for Patients Using Thiazolidinediones for Type 2 Diabetes: A Meta-Analysis

OBJECTIVE To clarify and quantify the effect of thiazolidinediones (TZDs; e.g., pioglitazone, rosiglitazone) on the risk of bladder cancer, other selected cancers, and overall cancer in patients with type 2 diabetes, we performed a systematic review and meta-analysis of observational studies. METHODS A PubMed/MEDLINE search was conducted for studies published in English up to June 30, 2012. Random-effect models were fitted to estimate summary relative risks (RR). RESULTS Seventeen studies satisfying inclusion criteria (3 case-control studies and 14 cohort studies) were considered. Use of TZDs was not associated to the risk of cancer overall (summary RR: 0.96; 95% confidence interval [CI]: 0.91-1.01). A modest excess risk of bladder cancer was reported in pioglitazone (RR: 1.20; 95% CI: 1.07-1.34 from six studies) but not in rosiglitazone (RR: 1.08; 95% CI: 0.95-1.23 from three studies) users. The RRs of bladder cancer were higher for longer duration (RR: 1.42 for >2 years) and higher cumulative dose of pioglitazone (RR: 1.64 for >28,000 mg). Inverse relations were observed with colorectal cancer (RR: 0.93; 95% CI: 0.90-0.97 from six cohort studies) and liver cancer (RR: 0.65; 95% CI: 0.48-0.89 from four studies), whereas there was no association with pancreatic, lung, breast, and prostate cancers. CONCLUSIONS Adequate evidence excludes an overall excess cancer risk in TZD users within a few years after starting treatment. However, there is a modest excess risk of bladder cancer, particularly with reference to pioglitazone. Assuming that this association is real, the potential implications on the risk-benefit analysis of TZD use should be evaluated.

Reduced discontinuation of antihypertensive treatment by two-drug combination as first step. Evidence from daily life practice.

Objectives To measure persistence with antihypertensive drug therapy in patients initiating treatment with mono or combination therapy. Methods Data analysis was based on two cohorts of patients, that is, a cohort derived from the registration of drug prescriptions in all residents of the Lombardy region receiving Public Health Service and a cohort of patients followed by general practitioners throughout the Italian territory. Data were limited to patients aged 40–80 years who received their first antihypertensive drug prescription (n = 433680 and 41199, respectively) in whom persistency of treatment was examined over 9 months. A proportional hazards model was fitted to estimate the association between the pattern of initial antihypertensive drug therapy and risk of treatment discontinuation. Data were adjusted for available potential confounders. Results Taking patients starting with diuretic monotherapy as reference, the adjusted risk of treatment discontinuation was progressively lower in patients starting with monotherapy other than a diuretic, a two-drug combination, including a diuretic and a two-drug combination without a diuretic. No significant difference in the risk of discontinuation was seen between extemporaneous and fixed dose combinations, including a diuretic, that is, the only combination reimbursable by Public Health Service and, thus, available in the database. Data were similar for the two cohorts. Conclusion Initiating treatment with a combination of two drugs is associated with a reduced risk of treatment discontinuation.

Evidence of tendinitis provoked by fluoroquinolone treatment: a case-control study.

AbstractObjective: To investigate the association between the use of fluoroquinolone agents and the risk of tendinitis in a large population-based case-control study. Methods: The study was performed by linking automated health databases from the Region of Lombardia, Italy. Cases were patients aged ≥18 years who had a hospital discharge diagnosis of non-traumatic tendinitis in 2002–3. For each case, up to five controls were randomly selected among those eligible for inclusion in the study. A conditional logistic regression model was used to estimate the odds ratio of tendinitis associated with the current, recent and past use of fluoroquinolones. Odds ratios were adjusted for exposure to other antibacterials and other drugs. Results: 22 194 cases and 104 906 controls met the inclusion criteria. Current use of fluoroquinolones significantly increased the risk of tendon disorders as a whole (odds ratio [OR] = 1.7; 95% CI 1.4, 2.0), tendon rupture (OR = 1.3; 95% CI 1.0, 1.8) and rupture of the Achilles’ tendon (OR = 4.1; 95% CI 1.8, 9.6). Concomitant use of corticosteroids and fluoroquinolones increased the risk of both tendon rupture (OR = 3.1; 95% CI 1.5, 6.3) and rupture of the Achilles’ tendon (OR = 43.2; 95% CI 5.5, 341.1). Discussion: Evidence that exposure to fluoroquinolones is associated with the sudden occurrence of tendinitis is supported by this large population-based study. We can estimate that a single case of rupture of the Achilles’ tendon would occur for every 5958 persons treated with fluoroquinolones (95% CI 2148, 23 085). The corresponding number needed to harm is 979 (95% CI 122, 9172) for patients who concomitantly use corticosteroids and 1638 (95% CI 351, 8843) for those aged >60 years. Conclusion: Clinicians should be aware of this adverse effect, and the increased risk for fluoroquinolone-associated tendinitis in elderly patients with corticosteroid use must be considered when these agents are prescribed.

Duration of Postoperative Delirium Is an Independent Predictor of 6‐Month Mortality in Older Adults After Hip Fracture

To evaluate the association between number of days with delirium and 6‐month mortality in elderly adults after hip fracture surgery.

Attributable risk for symptomatic liver cirrhosis in Italy

BACKGROUNDS/AIMS Knowledge of the proportion of liver cirrhosis attributable to the main risk factors is largely based on methodologically questionable clinical reports. METHODS The proportion of newly diagnosed cases of symptomatic liver cirrhosis attributable to known risk factors was estimated by a case-control study performed during 1989-1996 in 23 medical divisions of several hospitals distributed throughout Italy. Cases were 462 inpatients with cirrhosis admitted for the first time for liver decompensation. Controls were 651 patients admitted during the same period and to the same hospitals as the cases, for acute diseases unrelated to alcohol and virus infection. The proportion of symptomatic liver cirrhosis cases due to alcohol intake and hepatitis B and C viruses and the combination of these was expressed as the population attributable risk. RESULTS Attributable risks were 67.9% (95% confidence interval (CI): 53.8-79.4) for alcohol, 40.1% (95% CI: 35.3-45.2) for hepatitis C virus and 4.4% (95% CI: 2.5-7.6) for hepatitis B virus. The three factors together explained 98.1% (95% CI: 81.6-99.6) of cases in men and 67.0% (95% CI: 50.4-85.8) in women. CONCLUSIONS Alcohol is the risk factor with the highest impact on symptomatic liver cirrhosis risk in Italy. From a public health viewpoint, with the elimination of the well-known risk factors (particularly alcohol and hepatitis C virus), liver cirrhosis should become a rare disease.