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In vitro experiments with human liver microsomes and human hepatocytes suggest that a fraction of the administered dose (74% of an intravenous dose is excreted unchanged in the urine, leaving 25% for metabolism) is metabolized by cytochrome P450-dependent oxidation and subsequent glutathione conjugation to a variety of Phase II metabolites.

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The conclusion of the group is very clear in that the current time frame for treatment is supported by strong evidence.

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We placed significant emphasis on UPLIFT because it was the largest and longest randomized trial of tiotropium to date, mortality-related end points were prespecified, information on vital status was systematically collected and adjudicated, and mortality results were robust across different analyses.

SPIRIVA HandiHaler): two 1-year, placebo-controlled studies, two 6-month, placebo-controlled studies and two 1-year, ipratropium-controlled studies.

The patients were at least 40 years of age, with a forced expiratory volume in 1 second (FEV 1) of 70% or less after bronchodilation and a ratio of FEV 1 to forced vital capacity (FVC) of 70% or less.

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This medication should not be used more often than once daily.

Side effects include viral infection, bronchitis, chest infection, dizziness, anxiety, headache, sleep problems (insomnia), back pain, muscle cramps, sore throat, dry mouth, cough, stuffy nose, skin rash, itching, voice changes, chest pain, fast or pounding heartbeats, tremors, shaking, restless feeling, wheezing, choking, breathing problems, increased thirst or hunger, urinating more than usual, worsening in asthma symptoms.

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Aaron Miller, medical director of Mount Sinais Corinne Goldsmith Dickinson Center for Multiple Sclerosis in New York City.

These drugs (non-generic and all expensive) have a definite role in COPD, but not in treating the patient whose symptoms are acute, progressive or interfering with daily activity.

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The effect of SPIRIVA HANDIHALER on COPD exacerbations was evaluated in two clinical trials: a 4-year clinical trial described above and a 6-month clinical trial of 1829 COPD patients in a Veterans Affairs setting.

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Patients received either 18 μg of tiotropium or a matching placebo once daily, delivered through the HandiHaler inhalation device (Boehringer Ingelheim).

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The reduction in severe exacerbations was also significant: in a post hoc calculation, the number needed to treat in order to prevent one severe exacerbation during the 48-week treatment period was 15.

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Peter Morgan, at Yale School of Medicine, says there is substantial evidence that other cognitive enhancers, such as caffeine or nicotine, have benefits from shortterm use, but that those benefits are erased by longterm use, and are rather replaced by deficiencies in cognitive performance.

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These included potentially biased study selection, which was limited to trials reporting cardiovascular events; lack of assessment of patient follow-up time, with no accounting for differential discontinuation rates, which were significantly higher among patients given placebo (patients who continue to take placebo may be generally healthier than those who stop taking it, and potential differences in baseline cardiovascular risk factors were not accounted for in the analysis); lack of information on occurrence of adverse events in patients who withdrew from many of the included trials; lack of patient-level data; and the fact that trials on short-acting and long-acting anticholinergics were combined in the main analysis.

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