RAPID AND ULTRARAPID OPIOID DETOXIFICATION TECHNIQUES
Summary: Objective: To review the scientific literature on the effectiveness of rapid opioid detoxification (RD) (opioid withdrawal precipitated by naloxone hydrochloride or naltrexone) and ultrarapid opioid detoxification (URD) (opioid withdrawal precipitated by naloxone or naltrexone under anesthesia or heavy sedation) techniques. Data Sources: The MEDLINE database was searched from 1966 through 1997 using the indexing terms naloxone, naltrexone, substance dependence, and substance withdrawal syndrome. Additional data sources included bibliographies of papers identified on MEDLINE and bibliographies in textbooks on substance abuse. Study Selection: Inclusion criteria were studies of RD or URD, pharmacologic protocols specified, and clinical outcomes specified and reported. Exclusion criteria were unpublished data, data not in peer-reviewed journals, abstract-only publications, and review articles. Data Extraction: The methodologic characteristics of studies were extracted by the authors and summarized according to key components of research design concerning subject characteristics, therapy allocation, and outcomes assessed. Data Synthesis: A qualitative analysis was performed on the 12 studies of RD and the 9 studies of URD identified in our search. The RD studies enrolled 641 subjects (range for individual studies, 1-162): 7 were inpatient studies, and the protocols varied considerably, was did the outcomes assessed. Three RD studies included a control group, 2 used a randomized design, and 3 reported outcomes beyond 12 days. The URD studies enrolled 424 subjects (range for individual studies, 6-300): all were in patient studies, the detoxification and anesthesia protocols varied, 3 included a control group, 2 used a randomized design, and 2 reported outcomes for URD beyond 7 days. Conclusions: The existing literature on RD and URD is limited in terms of the number of subjects evaluated, the variation in protocols studied, lack of randomized design, and use of control groups, and the short-term nature of the outcomes reported. Further research is needed using more rigorous research methods, longer-term outcomes, and comparisons with other methods of treatment for opioid dependence.
Comment: Iran is
located at the cross-road of the opiate drug trafficking routes
between Asia and the West thus encumbered with considerable
opiate abuse which constitutes a major public health problem.
Consequently, the treatment of opiate dependents is of major
concern specially in regard to detoxification which plays a
critical role in the treatment regimens. Various methods of
detoxification are routinely used throughout world. Methadone
administration, for a 21-180 day period and buprenorphine
replacement with gradual tapering are among the most commonly
used methods with success rates ranging from 60-80%.
Due to local health policies, prescription of pure or partial
opiate agonists for detoxification are purposely prohibited in
Iran. In fact, drugs such as methadone or buronorphine are not
officially available. Thus the advocated treatment relies on
clonidine, an alpha-2 adrenergic agonist, which soothes
withdrawal symptoms. Clonidine has some major drawbacks such as
autonomic side effects and is ineffective on psychological
symptoms such as craving. In fact, success rates fall below 50%
in most instances and many substance abusers in Iran are
reluctant to participate in clonidine assisted detoxification
programs. Having these facts in mind, rapid and even ultra-rapid
techniques appear suitable alternatives for detoxification. The
success rate is thus increased, less suffering is experienced and
the patients are more enthusiastic and compliant. Rapid and
ultra-rapid detoxification are attainable with available drugs
and there is no need to resort to pure or partial agonists. For
countries like Iran that wish to restrict public access to
agonistic drugs, these methods offer a promising alternative. As
has been stated in the above review, the results of these methods
are still somewhat ambiguous and one should invest academic
resources for further assessing the effectiveness, safety and
ethics of developing rapid methods of detoxification in Iran.
Azarakhsh Mokri, MD,
Tehran
Source: O-Connor PG; Kosten TR. JAMA 1998;279(3):229-34.
HOMOCYSTEINE AND ISCHEMIC HEART DISEASE: RESULTS OF A PROSPECTIVE STUDY WITH IMPLICATIONS REGARDING PREVENTION
Summary: Background: Results from prospective studies of serum homocysteine levels and ischemic heart disease (IHD) are inconclusive. We carried out a further prospective study to help clarify the position. Methods: In the British United Provident Association (BUPA) prospective study of 21,520 men aged 35 to 64 years, we measured homocysteine levels in stored serum samples and analyzed data from 229 men without a history of IHD at study entry who subsequently died of IHD and 1126 age-matched control subjects (nested case-control design). Results: Serum homocysteine levels were significantly higher in men who died of IHD than in men who did not (mean, 13.1 vs 11.8 micromol/L; p<0.001). The risk of IHD among men in the highest quartile of serum homocysteine levels was 3.7 times (or 2.9 times after adjusting for other risk factors) the risk among men in the lowest quartile (95% confidence interval [Cl], 1.8-4.7). There was a continuous dose response relationship, with risk increasing by 41% (95% Cl, 20%-65%) for each 5 micromol/L increase in the serum homocysteine level. After adjustment for apoliporprotein B levels and blood pressure, this estimate was 33% (95% Cl, 22%-59%). In a meta-analysis of the retrospective studies of homocysteine level and myocardial infarction, the age-adjusted association was stronger: an 84% (95% Cl, 52%-123%) increase in risk for a 5-micromol/L increase in the homocysteine level, possibly because the participants were younger; the relationship between serum homocysteine level and IHD seems to be stronger in younger persons than in older persons. Conclusions: Our positive results help resolve the uncertainty that resulted from previous prospective studies. The epidemiological, genetic, and animal evidence together indicate that the association between serum homocysteine level and IHD is likely to be causal. A general increase in consumption of the vitamin folic acid (which reduces serum homocysteine levels) would, therefore, be expected to reduce mortality from IHD.
Comment:
Homocysteine acts as an atherogenic and thrombophilic agent. An
increase in total plasma homocysteine level is an independent
risk factor for coronary, cerebrovascular, and peripheral
arterial disease. The mechanism of atherogenic and thrombophilic
effects of homocysteine is still unknown. However, endothelial
dysfunction, alteration of nitric oxide release or signaling,
stimulation of smooth muscle cell proliferation, modification of
the extracellular matrix, and lipoprotein oxidation have all been
proposed by various researchers.
It was shown that folic acid, vitamin B12, and
pyridoxine can result in significant decrease of total plasma
homocysteine level. The prevalence of vitamin B12 or
folate deficiency in developing countries, is higher than in the
West because of a higher prevalence of under-nutritional states
and parasitic infestations. As a consequence, homocysteinemia is
expected to be more prevalent among these communities. One may
conclude that in developing countries, many patients who have
coronary artery disease, reducing homocysteine by vitamin
supplementation, may decrease the rate of cardiovascular events.
Bahram Aminian, MD,
Shiraz
Source: Wald NJ, Watt HC, Law MR, et al. Arch Intern Med
1998;158:862-7.
CHANGES IN QUALITY OF LIFE AFTER RENAL TRANSPLANTATION.
Summary: The objective of this study was to evaluate the modifications that renal transplantation produces on the quality of life (QOL) of patients with chronic renal failure (CRF) previously undergoing hemodialysis (HD) and to analyze the possible factors implicated. A multicenter study of QOL was performed on 1,023 patients undergoing dialysis, using as QOL indicators the Karnofsky Scale (KS) and the Sickness Impact Profile (SIP). Among this group, 93 patients received a renal transplant and QOL was re-studied in them; each subject, therefore, was his own control. In the 88 patients with a functioning graft, an improvement in QOL indices was globally observed; this improvement was much more marked in men than in women, for unclear reasons. Older age and greater prior comorbidity diminished the beneficial effects of transplantation.
Comment: Owing to the technical advances and improved success rates, renal transplantation has enjoyed a rapid expansion, and has led to a serious organ shortage worldwide. Meanwhile, there is an increasing concern in regard to economical, cultural and ethical consequences of such explosive expansion, particularly in developing countries, where the problem is confounded by limited medical facilities. It is not known whether modifications provided in the quality of life in hemodialysis patients justifies such a costly high-tech medicine in developing communities. Moreover, in countries where living organ-donation is the main source of allograft supply, inevitable competition for human organs might increase the gap in health care delivery between the poor and the rich, due to the inevitable problems inherent in the commercial principle of demand and offer. Vulnerable people, in need of money may serve as paid organ donors, which is ethically undesirable. In addition, living organ-donation prompted by economical motives, and using human organs as spare parts may adversely influence respect for the human body and human dignity in those communities. To deal with the problem, it is mandatory to encourage living related and discourage living non-related organ donation in developing countries whilst formulating new legislation promoting cadaveric organ donations.
Parviz Khajehdehi, M.D.,
Shiraz
Source: Jofre R, Lopez-Gomez JM, Moreno F, et al. Am J
Kidney Dis 1998;32(1):93-100.