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Objective To report an integrated analysis of two previous studies fully characterizing the clinical utility of the controlled-release gastrointestinal therapeutic system (GITS) formulation of doxazosin in the treatment of benign prostatic hyperplasia (BPH). Patients and methods Two pivotal randomized, doubleblind studies of doxazosin GITS for BPH were assessed by an integrated analysis. Both studies included a 2-week washout period, a 2-week single-blind placebo run-in phase, and a 13-week double-blind treatment phase.One study compared doxazosin GITS, doxazosin standard (-S) and placebo in 795 men; the other compared doxazosin GITS and doxazosin-S in 680 men. Doxazosin GITS was initiated at 4 mg once daily and titrated to 8 mg once daily after 7 weeks, and doxazosin-S was initiated at 1 mg once daily and titrated to a maximum of 8 mg once daily over 7 weeks as needed to achieve optimal symptom control. The primary outcome measures were mean changes from baseline to the ®nal visit for the International Prostate Symptom Score (IPSS) and maximum urinary¯ow rate (Q max ) in the per-protocol population. Numerous symptom-and urinary-related secondary outcomes were assessed, as were effects of therapy on male erectile dysfunction measured using the International Index of Erectile Function (IIEF) in one study. Results Both doxazosin GITS and doxazosin-S signi®-cantly improved the symptoms of BPH, as shown by a 45% reduction for each in total IPSS from baseline to ®nal visit, compared with a 34% reduction in patients on placebo. Doxazosin GITS and doxazosin-S produced comparable improvements in Q max that were signi®-cantly greater than with placebo, with a greater improvement sooner after treatment with doxazosin GITS than with doxazosin-S. Nearly half of the patients on doxazosin GITS had symptom relief at the 4-mg starting dose. A similar number of patients in both doxazosin groups were titrated to the maximum dose. Secondary outcomes were consistent with the primary effects. Both doxazosin GITS and doxazosin-S produced signi®cant improvements in sexual function according to IIEF scores among those with dysfunction at baseline. The overall incidence of adverse events was similar among patients treated with doxazosin GITS and placebo, and slightly lower than those on doxazosin-S. There was no apparent difference in the type of adverse events reported for the two formulations of doxazosin, although most adverse events were reported at a lower frequency with doxazosin GITS. Conclusion Doxazosin GITS is signi®cantly more effective than placebo in reducing the clinical symptoms of BPH and improving Q max , and as effective as doxazosin-S. Both doxazosin formulations improved sexual function in patients with BPH and sexual dysfunction at baseline. Doxazosin GITS produced a therapeutic effect equivalent to that of doxazosin-S, but with fewer titration steps and a slightly lower overall incidence of adverse events.

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Adverse drug reactions (ADR) to disulfiram treatment have been reported as single cases, but few systematic investigations exist. In this study we analysed the spontaneous ADR reports to the Danish Committee on Adverse Drug Reactions during 1968-1991. In that period 154 ADRs to disulfiram were reported, mainly of hepatic, neurological, skin, and psychiatric reactions, in decreasing order of frequency. The safety of disulfiram, estimated on the amount produced and the number of reactions reported, corresponds to an intermediate rate of adverse reactions (1 per 200-2000 treatment year). Over the 23-year period, 14 deaths were reported in Denmark and this corresponds to a rate of 1 per 25,000 treatment year; the chief cause was liver toxicity. Reports to the WHO collaborating Centre for International Drug Monitoring in Uppsala, Sweden, showed the same ADR profile, although with a higher rate of neurological and psychiatric and a lower rate of hepatic reactions. differed according to organ. Hepatitis occurred with a distinct peak after 2 months of treatment, skin reactions peaked after 2 weeks, and the rate of neurological ADR increased with duration of therapy. The relation of skin reactions and hepatitis t o nickel allergy is discussed, as is the dose-dependency of neuropathy.Concomitant disulfiram treatment affects the metabolism of several drugs and the dynamics of others, leading to a number of clinically important drug interactions. The disulfiram drug interactions are reviewed.The latency time from the start of treatment to the manifestion of the ADR

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Are social inequalities in health unjust when brought about by differences in lifestyle? A widespread idea, luck egalitarianism, is that inequality stemming from individuals' free choices is not to be considered unjust, since individuals, presumably, are themselves responsible for such choices. Thus, to the extent that lifestyles are in fact results of free choices, social inequality in health brought about by these choices is not in tension with egalitarian justice. If this is so, then it may put in question the justification of free and equal access to health care and existing medical research priorities. However, personal responsibility is a highly contested issue and in this article we first consider the case for, and second the case against, personal responsibility for health in light of recent developments in philosophical accounts of responsibility and equality. We suggest-but do not fully establish-that at the most fundamental level people are never responsible in such a way that appeals to individuals' own responsibility can justify inequalities in health.