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Naltrexone maintenance treatment for opioid dependence.

BACKGROUND: Despite widespread use of naltrexone maintenance in many countries for more than ten years now (e.g., USA since 1984, UK since 1988) a sound documentation of the research on this drug is still missing. OBJECTIVES: To evaluate the effects of naltrexone maintenance treatment in preventing relapse in opioid addicts after detoxification. SEARCH STRATEGY: We searched MEDLINE, EMBASE, CCTR and handsearched the "Bolletino per le Farmacodipendenze e l'Alcolismo"; contact was sought with pharmaceutical producers of naltrexone, with authors and other CRGs; references of obtained studies. Trials were reliably identified and data extracted. Date of most recent searches: June 1998. SELECTION CRITERIA: All studies controlled for naltrexone; treatment of heroin addicts after detoxification with naltrexone. Studies were classified into three categories (high, moderate or low risk of bias) according to their methodological quality. DATA COLLECTION AND ANALYSIS: Reviewers evaluated data independently and analysed outcome measures taking into consideration adherence to and success of the study intervention. Data was extracted and analysed stratifying for the three categories of study quality. Where possible, meta-analysis was performed. MAIN RESULTS: Eleven studies were included in this review, and not all of them were randomised. Meta-analysis could be done to a low degree only, because the studies and their outcomes were very heterogeneous. The result of this quantitative analysis was statistically poor, and so was the methodological quality of the included studies. REVIEWER'S CONCLUSIONS: The available trials do not allow a final evaluation of naltrexone maintenance treatment yet. A trend in favour of treatment with naltrexone was observed for certain target groups, as described in the literature before. A well-done clinical trial is needed in order to get better evidence as soon as possible.

Humans↗

Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence.

BACKGROUND: Buprenorphine has recently been reported to be an alternative to methadone and LAAM for maintenance treatment of opioid dependent individuals, differing results are reported concerning its relative effectiveness indicating the need for an integrative review. OBJECTIVES: To evaluate the effects of buprenorphine maintenance against placebo and methadone maintenance in retaining patients in treatment and in suppressing illicit drug use. SEARCH STRATEGY: We searched the following databases up to 2001, inclusive: Cochrane Drugs and Alcohol Review Group Register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, Current Contents, Psychlit, CORK [www. state.vt.su/adap/cork], Alcohol and Drug Council of Australia (ADCA) [www.adca.org.au], Australian Drug Foundation (ADF -VIC) [www.adf.org.au], Centre for Education and Information on Drugs and Alcohol (CEIDA) [www.ceida.net.au], Australian Bibliographic Network (ABN), and Library of Congress databases, available NIDA monographs and the College on Problems of Drug Dependence Inc. proceedings, the reference lists of all identified studies and published reviews and authors of identified RCT's were asked about any other published or unpublished relevant RCT. SELECTION CRITERIA: Randomised clinical trials of buprenorphine maintenance compared with either placebo or methadone maintenance for opioid dependence. DATA COLLECTION AND ANALYSIS: Reviewers evaluated the papers separately and independently, rating methodological quality of concealment of allocation; data were extracted independently for meta-analysis and double-entered. MAIN RESULTS: Thirteen studies met the inclusion criteria, all were randomised clinical trials, all but one were double-blind. The method of concealment of allocation was not clearly described in 11 of the studies, otherwise methodological quality was good. Buprenorphine given in flexible doses appeared statistically significantly less effective than methadone in retaining patient in treatment (RR= 0.82; 95% CI: 0.69-0.96). Low dose buprenorphine is not superior to low dose methadone. High dose buprenorphine does not retain more patients than low dose methadone, but may suppress heroin use better. There was no advantage for high dose buprenorphine over high dose methadone in retention (RR=0.79; 95% CI:0.62-1.01), and high dose buprenorphine was inferior in suppression of heroin use. Buprenorphine was statistically significantly superior to placebo medication in retention of patients in treatment at low doses (RR=1.24; 95% CI: 1.06-1.45), high doses (RR=1.21; 95% CI: 1.02-1.44), and very high doses (RR=1.52; 95% CI: 1.23-1.88). However, only high and very high dose buprenorphine suppressed heroin use significantly above placebo. REVIEWER'S CONCLUSIONS: Buprenorphine is an effective intervention for use in the maintenance treatment of heroin dependence, but it is not more effective than methadone at adequate dosages.

Buprenorphine↗

Three- or four- versus two-drug antiretroviral maintenance regimens for HIV infection.

BACKGROUND: Combination antiretroviral therapy administered to HIV-infected individuals has been shown to improve immunologic function and delay the progression of HIV infection. However, because patient adherence to complicated combination-therapy antiretroviral regimens is difficult and because of concerns regarding cumulative toxicity of antiretroviral drugs, regimens that utilize fewer antiretroviral agents are desirable. OBJECTIVES: To compare the use three- or four- versus two-drug antiretroviral maintenance regimens following successful induction therapy for HIV infection. SEARCH STRATEGY: The following electronic databases were searched for relevant randomized trials or reviews: 1. MEDLINE for the years 1982-1999 using the search terms human immunodeficiency virus, antiretroviral therapy, maintenance therapy, zidovudine, lamivudine, indinavir, stavudine, saquinivir, nelfinavir, didanosine, zalcitabine, ritonovir, AIDS, anti-HIV agents, HIV infection and HIV seropositivity 2. AIDSLINE for the years 1982-1999 using the search terms antiretroviral therapy, maintenance therapy, zidovudine, lamidvudine, indinavir, stavudine, saquinivir, nelfinavir, didanosine, zalcitabine, ritonovir, anti-HIV agents 3. The Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness and the Cochrane Clinical Trials Register in the Cochrane Library, Issue 2, 1999. 4. The specialist register of trials maintained by the Cochrane Collaborative Review Group on HIV Infection and AIDS 5. AIDSTRIALS, a specialist registry of current and completed trials maintained by the U.S. National Library of Medicine The abstracts of relevant conferences, including the International Conferences on AIDS, the Conference on Retroviruses and Opportunistic Infections, the Infectious Disease Society of America annual meeting and the Interscience Conference on Antimicrobial Agents and Chemotherapy, as indexed by AIDSLINE, were also reviewed. All reference lists of all review articles and primary articles identified were searched. SELECTION CRITERIA: Randomized controlled trials in which HIV-infected adults who had successfully completed three- or four-drug antiretroviral induction therapy were randomized to maintenance therapy with three or four drugs or maintenance therapy with two drugs. Successful induction therapy was defined by a plasma viral load of less than 500 copies/ml. DATA COLLECTION AND ANALYSIS: Two reviewers assessed eligibility and trial quality. Attempts were made to contact the authors of the included abstract. Data on the number of patients experiencing loss of viral suppression were abstracted by two reviewers. The data were pooled, where appropriate, to yield odds ratios, using random effects models. MAIN RESULTS: Four trials were identified including three published studies and one abstract. Compared to three- or four-drug maintenance therapy, maintenance therapies including fewer drugs were associated with a higher risk of virologic failure (loss of HIV suppression to non-detectable levels). Combining the results of all four studies yielded an odds ratio of 5.55 (95% confidence interval, 3.14 - 9.80). Similar results were obtained when the one abstract was excluded (odds ratio, 5.48; 95% confidence interval, 2.82 - 10.65). Performing subgroup analyses of studies using the same induction and maintenance regimens gave similar results. Maintenance regimens of zidovudine and lamivudine compared to maintenance regimens with zidovuine, lamivudine and indinavir, were associated with significantly higher rates of virologic failure (odds ratio, 4.57; 95% confidence interval, 1.80 - 11.58). Similarly, maintenance regimens that discontinued one or more protease inhibitor after including them in induction therapy were also associated with a significantly higher risk of virologic failure (odds ratio, 6.15; 95% confidence interval, 3.40 -11.10). (ABSTRACT TRUNCATED)

Anti-HIV Agents↗

Lithium for maintenance treatment of mood disorders.

BACKGROUND: Mood disorders are common, disabling and tend to be recurrent. They carry a high risk of suicide. Maintenance treatment, aimed at the prevention of relapse, is therefore of vital importance. Lithium has been used for some years as the mainstay of maintenance treatment in bipolar affective disorder, and to a lesser extent in unipolar disorder. However, the efficacy and effectiveness of prophylactic lithium therapy has been disputed. Low suicide rates in lithium-treated patients have led to claims that lithium has a specific anti-suicidal effect. If so, this is of considerable importance as treatments for mental disorders in general have not been shown convincingly to be effective in suicide prevention. OBJECTIVES: 1. To investigate the efficacy of lithium treatment in the prevention of relapse in recurrent mood disorders. 2. To examine the effect of lithium treatment on consumers' general health and social functioning, its acceptability to consumers, and the side-effects of treatment. 3. To investigate the hypothesis that lithium has a specific effect in reducing the incidence of suicide and deliberate self-harm in persons with mood disorders. SEARCH STRATEGY: The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR) and The Cochrane Controlled Clinical Trials Register (CCTR) were searched. Reference lists of relevant papers and major text books of mood disorder were examined. Authors, other experts in the field and pharmaceutical companies were contacted for knowledge of suitable trials, published or unpublished. Specialist journals concerning lithium were hand searched. SELECTION CRITERIA: Randomised controlled trials comparing lithium with placebo, where the stated intent of treatment was maintenance or prophylaxis. Participants were males and females of all ages with diagnoses of mood disorder. Discontinuation studies (in which all participants had been stable on lithium for some time before being randomised to either continued lithium treatment or placebo substitution) were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted from the original reports independently by two reviewers. The main outcomes studied were related to the objectives stated above. Data were analysed for all diagnoses of mood disorder and for bipolar and unipolar disorder separately. Data were analysed using Review Manager version 4.0. MAIN RESULTS: Nine studies were included in the review, reporting on 825 participants randomly allocated to lithium or placebo. Lithium was found to be more effective than placebo in preventing relapse in mood disorder overall, and in bipolar disorder. The most consistent effect was found in bipolar disorder (random effects OR 0.29; 95% CI 0.09 to 0.93 ). In unipolar disorder, the direction of effect was in favour of lithium, but the result (when heterogeneity between studies was allowed for) did not reach statistical significance. Considerable heterogeneity was found between studies in all groups of patients. The direction of effect was the same in all studies; no study found a negative effect for lithium. Heterogeneity may have been due to differences in selection of participants, and to differing exposures to lithium in the pre-study phase resulting in variable influence of a discontinuation effect. There was little reported data on overall health and social functioning of participants under the different treatment conditions, or on the participants' own views of their treatment. Descriptive analysis showed that assessments of general health and social functioning generally favoured lithium. Small absolute numbers of deaths and suicides, and the absence of data on non-fatal suicidal behaviours, made it impossible to draw meaningful conclusions about the place of lithium therapy in suicide prevention. REVIEWER'S CONCLUSIONS: This systematic review indicates that lithium is an efficacious maintenance treatment for bipolar disorder. In unipolar disorder the evidence of efficacy is less robust. This review does not cover the relative efficacy of lithium compared with other maintenance treatments, which is at present unclear. There is no definitive evidence from this review as to whether or not lithium has an anti-suicidal effect. Systematic reviews and large scale randomised studies comparing lithium with other maintenance treatments (e.g. anti-convulsants, antidepressants) are necessary. Outcomes relating to death and suicidal behaviour should be included in all future maintenance studies of mood disorder.

Antimanic Agents↗

Adjustable maintenance dosing with budesonide/formoterol in a single inhaler provides effective asthma symptom control at a lower dose than fixed maintenance dosing.

Asthma guidelines suggest a stepwise approach to maintenance pharmacological treatment of persistent asthma until control is attained, and a 3 month review of the fixed maintenance dosing for step-up or step-down adjustment. This 12-week study compared the efficacy and safety of budesonide/formoterol in a single inhaler (Symbicort Turbuhaler 160/4.5 or 80/4.5 microg) given as adjustable maintenance or fixed maintenance dosing. Patients (n = 2358) were randomised to budesonide/formoterol fixed maintenance dosing (two inhalations bid) or adjustable maintenance dosing (two inhalation bid; stepping up to four inhalations bid if asthma worsened for a maximum of 14 days; stepping down to two inhalations once nocte or one inhalation bid if symptoms were controlled) for 12 weeks, following a 4-week run-in period on budesonide/formoterol two inhalations bid. Primary efficacy variables were frequency of asthma exacerbations and changes in patients' asthma symptom severity. Secondary variables were asthma control, safety and health economics. Both adjustable maintenance dosing and fixed maintenance dosing were associated with similar low frequency of exacerbations (5% both groups; ns) and similarly improved lung function, with similarly fewer nocturnal awakenings and less asthma symptoms compared with the mean value of the run-in period. However, patients on adjustable maintenance dosing used 24% fewer study drug compared with fixed maintenance dosing (2.95 versus 3.86 inhalations daily; p < 0.0001) and incurred in a significant (p <0.0001) reduction in total costs (direct+indirect) compared with fixed maintenance dosing. In conclusion, adjustable maintenance dosing with budesonide/formoterol effectively controls asthma at a reduced drug load with lower costs than fixed maintenance dosing.

Adult↗

Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence.

BACKGROUND: Methadone maintenance was the first widely used form of opioid replacement therapy developed to treat heroin dependence, and it remains the best-researched treatment for this problem. Despite the widespread use of methadone in maintenance treatment for opioid dependence in many countries, it is a controversial treatment whose effectiveness has been disputed. OBJECTIVES: To evaluate the effects of methadone maintenance treatment (MMT) compared with treatments that did not involve opioid replacement therapy (i.e., detoxification, offer of drug-free rehabilitation, placebo medication, wait-list controls) for opioid dependence. SEARCH STRATEGY: We searched all the following databases up to 2001: Cochrane Drugs and Alcohol Review Group Register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, Current Contents, Psychlit, CORK [www. state.vt.su/adap/cork], Alcohol and Drug Council of Australia (ADCA) [www.adca.org.au], Australian Drug Foundation (ADF-VIC) [www.adf.org.au], Centre for Education and Information on Drugs and Alcohol (CEIDA) [www.ceida.net.au], Australian Bibliographic Network (ABN), and Library of Congress databases, available NIDA monographs and the College on Problems of Drug Dependence Inc. proceedings, the reference lists of all identified studies and published reviews; authors of identified RCTs were asked about other published or unpublished relevant RCTs. SELECTION CRITERIA: All randomised controlled clinical trials of methadone maintenance therapy compared with either placebo maintenance or other non-pharmacological therapy for the treatment of opioid dependence. DATA COLLECTION AND ANALYSIS: Reviewers evaluated the papers separately and independently, rating methodological quality of concealment of allocation, data were extracted independently for meta-analysis and double-entered. MAIN RESULTS: Six studies met the criteria for inclusion in this review, all were randomised clinical trials, two were double-blind. There were a total number of 954 participants. The method of concealment of allocation was inadequate in one study, not clearly described in four studies, but adequate in a sixth study. Based on the meta-analysis, methadone appeared statistically significantly more effective than non-pharmacological approaches in retaining patient in treatment (3 RCTs, RR=3.05; 95%CI: 1.75-5.35) and in the suppression of heroin use (3 RCTs, RR=0.32; 95%CI: 0.23-0.44), but not statistically in criminal activity (3 RCTs, RR=0.39; 95%CI: 0.12-1.25). REVIEWER'S CONCLUSIONS: Methadone is an effective maintenance therapy intervention for the treatment of heroin dependence as it retains patients in treatment and decreases heroin use better than treatments that do not utilise opioid replacement therapy. It does not show a statistically significant superior effect on criminal activity.

Humans↗

Leisure-time activity is an important determinant of long-term weight maintenance after weight loss in the Sibutramine Trial on Obesity Reduction and Maintenance (STORM trial).

BACKGROUND: The success rate of long-term maintenance of weight loss in obese patients is usually low. To improve the success rate, determinants of long-term weight maintenance must be identified. OBJECTIVE: The objective of the study was to identify determinants of long-term success in weight maintenance in obese subjects who completed the Sibutramine Trial on Obesity Reduction and Maintenance (n = 261), a multicenter European study of weight loss and weight maintenance in obesity that combines sibutramine treatment with dietary restriction and advice on exercise and behavior. DESIGN: We studied weight maintenance over 18 mo in subjects who had completed a 6-mo weight-loss phase. Factors included in the analysis were initial body weight, the percentage of initial body weight lost, dietary intake, various components of physical activity (measured with the Baecke questionnaire), the type of treatment (sibutramine or placebo), age, and sex. RESULTS: Multiple regression analysis identified treatment group (sibutramine or placebo), the percentage of the initial body weight that was lost during the 6-mo weight-loss phase, and the leisure-time physical activity index as significant determinants of weight maintenance. Together, these 3 factors explained 20% of the variation in weight maintenance (P < 0.001). Dietary factors, age, and sex were not significant predictors of weight-maintenance success in this study. CONCLUSIONS: Weight-maintenance success after weight loss is positively influenced by sibutramine treatment during weight maintenance, by a greater initial weight loss, and by a higher leisure-time physical activity index, which reflects higher levels of activities such as walking and cycling and lower levels of television viewing.

Adolescent↗

Heroin maintenance for chronic heroin dependents.

BACKGROUND: Dependent heroin users are characterised by the persistence of use in spite of the difficulties they experience with health, law, social achievements and personal relationships. The present review will consider maintenance treatment in which the patients enter programs of pharmacological administration tailored to achieve patient stabilisation. Many medications have been used for this purpose such as: Methadone, Buprenorphine and LAAM. The present review will focus on maintenance treatment through the prescription of heroin. OBJECTIVES: To assess the efficacy and acceptability of heroin maintenance versus methadone or other substitution treatments for opioid dependence, in retaining patients in treatment; reducing the use of illicit substances and improving health and social functioning. SEARCH STRATEGY: The Cochrane Central Register of Trials (CENTRAL) issue 4, 2002; MEDLINE (on Silver Platter) 1966-2002; EMBASE (on OVID) 1980-2000 and CINAHL till 2000 were searched. There was no language or publication year restrictions. Many researchers were contacted for information. SELECTION CRITERIA: Randomised controlled trials of heroin (alone or combined with methadone) maintenance treatment compared with any other pharmacological treatments. DATA COLLECTION AND ANALYSIS: The trials were independently assessed for inclusion and methodological quality by the reviewers. Data were extracted independently and double checked. Studies were not pooled together because of heterogeneity. MAIN RESULTS: 2400 references were obtained and 20 studies were eligible, 4 met the inclusion criteria for a total of 577 patients. The studies included could not be analysed cumulatively because of heterogeneity of interventions and outcomes considered. Two studies compared injected heroin to oral methadone for 1 year (270 patients) but considered different outcomes; one study compared injected heroin and methadone to oral methadone for 6 months (51 patients); and one compared inhaled heroin and methadone to oral methadone for 1 year (235 patients). Retention in treatment: in two studies there was no statistical difference between groups; one study (N=90) had a RR=2.49 (95% CI 1.51-4.10) in favour of heroin; one study (N=235) had a RR 0.79 (95%CI 0.68-0.90) in favour of methadone. Relapse to illegal heroin use, based on self report: in one study the proportion of people still using heroin were 64% in the heroin group, 59% methadone group; in the other study the RR was 0.33 (95%CI 0.15-0.72) in favour of heroin. The remaining studies did not provide the data. Criminal offence: one of the two studies which provided details about this showed the potential of heroin prescription in reducing the risk of being charged RR 0.32 (95% CI 0.14-0.78). Social functioning: the two studies reporting this outcome did not show statistical difference between intervention groups. The two most recent studies considered criminal offence and social functioning as part of a multidomain outcome measure and showed higher improvement among those treated with heroin plus methadone over those on methadone only. REVIEWER'S CONCLUSIONS: No definitive conclusions about the overall effectiveness of heroin prescription is possible because of non-comparability of the experimental studies available to be included in this review. Results favouring heroin treatment come from studies conducted in countries where the treatment system is comprehensive and easy accessible Methadone Maintenance Treatment at effective dosages is available. In those studies heroin prescription was addressed to patients who had failed previous methadone treatments.

Heroin↗

A randomized comparison of standard chemotherapy versus alternating chemotherapy and maintenance versus no maintenance therapy for extensive-stage small-cell lung cancer: a phase III study of the Eastern Cooperative Oncology Group.

The present randomized, prospective study was designed to assess whether alternating induction cyclophosphamide, doxorubicin, vincristine-altretamine (hexamethylmelamine), etoposide, and methotrexate (CAV-HEM) chemotherapy is better than standard chemotherapy (CAV) in improving response, survival, and remission time in 577 evaluable patients having extensive-disease small-cell lung cancer (SCLC). In addition, the study was designed to assess the impact of maintenance chemotherapy following a complete response (CR) on the time to progression and survival. The response rates (CR plus partial response [PR]) for CAV-HEM and CAV were 64% and 61%, respectively, but 23% of the patients on CAV-HEM achieved a CR compared with 16% for CAV alone (P = .03). Among complete responders, the continuation of therapy significantly increased the remission time for patients on CAV, while maintenance therapy for patients on CAV-HEM had no significant impact on remission time. However, the increased remission had little effect on survival. Patients on CAV maintenance therapy survived marginally longer than those patients on no maintenance therapy, whereas patients who received CAV-HEM and no maintenance therapy survived longer than those on maintenance therapy. CAV-HEM was associated with significantly higher severity of complications (ie, mainly myelosuppression) than CAV (P = .01). Maintenance chemotherapy was associated with significantly more complications than no maintenance therapy. Patients on CAV-HEM lived significantly longer than those on CAV alone (45.9 weeks v 42.7 weeks; P = .002). Ten percent of patients treated on CAV-HEM survived at least 2 years, compared with 4% on CAV alone. In our study involving patients with extensive-disease SCLC, the alternating induction chemotherapy significantly increased the CR rates and had a small impact on long-term survival compared with the results achieved with standard induction chemotherapy. Moreover, when the alternating induction chemotherapy was used, long-term maintenance chemotherapy was not needed.

Aged↗

Duration of remission during maintenance cyclosporine therapy for psoriasis. Relationship to maintenance dose and degree of improvement during initial therapy.

BACKGROUND: Cyclosporine therapy is highly effective in the treatment of psoriasis. To minimize side effects, the lowest effective dosage for maintenance therapy should be sought. METHODS: We selected 61 patients who had achieved clearing or near-clearing of psoriasis during an induction phase of cyclosporine therapy. We then randomly assigned them in a double-blind fashion to receive one of two dosages of cyclosporine (1.5 or 3 mg/kg per day) or placebo for maintenance treatment. For each patient, the time to relapse was the time from the start of maintenance therapy until the patient showed a two-point worsening of psoriasis on a seven-point scale, up to a maximum of 4 months, when the study ended. RESULTS: Sixty patients completed the maintenance study. The mean time to relapse was significantly longer in the 3-mg/kg group (12 +/- 1 weeks) than in the 1.5-mg/kg group (9 +/- 1 weeks; P = .04) and the placebo group (7 +/- 1 weeks; P = .002); the latter two groups were not significantly different (P = .3). When the study ended, 57% of the 3-mg/kg group had not relapsed, compared with 21% and 5% of the 1.5-mg/kg and placebo groups, respectively. The following factors were associated with longer remissions: less psoriasis at the start of maintenance dosing (r = .40, P = .002); lower dosage of cyclosporine to achieve clearing or near-clearing during induction (r = -.30, P = .02); higher maintenance dosing (r = .38, P = .004); and smaller differences between the induction and maintenance dosages (r = -.41, P = .002). Patients' laboratory values improved compared with those at induction, and no patient experienced important clinical side effects during maintenance dosing. CONCLUSIONS: After clearing or near-clearing is achieved in patients with severe psoriasis, 3 mg/kg per day is a reasonable dosage to choose for maintenance. Patients who are more responsive to cyclosporine (as measured by greater clearing of psoriasis at lower induction dosages) tend to have longer remissions.

Adult↗

Exposure assessment of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in temporary municipal-waste-incinerator maintenance workers before and after annual maintenance.

Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) have been found in ambient air around municipal waste incinerators (MWIs), and elevated serum levels in incinerator workers have also been observed in some studies. However, few studies have focused on temporary employees who work intermittently through the annual maintenance and clean-up around different incinerators. The present study aimed to assess the change in serum PCDD/F levels of temporary employees between the beginning of periodic incinerator maintenance and one month the work was completed. Thirty-five volunteer workers, most of them transient and temporary maintenance staff, were recruited from a contractor that provided annual maintenance for four incinerators in this study. Information about each participant was obtained by questionnaire at the beginning of annual maintenance. The questionnaire asked for work history, health status, and diet information. As measured by the PCDD/F levels in blood, a significant increase was observed in workers after a month of maintenance work. The increase was greater in workers who had never done this type of maintenance than in those with previous experience, especially for 2,3,4,6,7,8-HxCDF levels. The data also showed that the laborers and employers need to pay more attention to occupational health issues even for short-term incinerator maintenance workers.

Adult↗

Psychosocial combined with agonist maintenance treatments versus agonist maintenance treatments alone for treatment of opioid dependence.

BACKGROUND: Methadone maintenance at proper doses is effective in retaining patients in treatment and suppressing heroin use. Questions remain regarding the efficacy of the psychosocial services that are offered by most maintenance programs. OBJECTIVES: To evaluate the effectiveness of any psychosocial plus any agonist maintenance treatment versus any agonist treatment alone in retaining patients in treatment, reducing the use of substances and improving health and social status. SEARCH STRATEGY: We searched the Cochrane Central Register of Trials (CENTRAL) issue 3, 2003; MEDLINE 1966-2003; EMBASE 1980-2003; PsycINFO 1985-2003; relevant web sites; scan of reference list of relevant articles. There were no language or publication restrictions. SELECTION CRITERIA: RCTs which focus on any psychosocial plus any agonist compared to any agonist maintenance intervention for opiate dependence. People aged less than 18 and pregnant women were excluded. Psychosocial in combination with antagonist maintenance treatment are excluded too. DATA COLLECTION AND ANALYSIS: The trials were independently assessed for inclusion and methodological quality by the reviewers. Data were extracted independently and double checked. MAIN RESULTS: The searching process resulted in the identification of 77 different studies: 12 studies met the inclusion criteria. These studies considered 8 different psychosocial interventions and 1 pharmacological treatment: Methadone Maintenance (MMT). The results show additional benefit in adding any psychosocial treatment to standard methadone maintenance treatment in relation to the use of heroin during the treatment RR 0.69 (95% CI 0.53-0.91); no statistically significant additional benefit was shown in terms of retention in treatment RR 0.94 (95% CI 0.85-1.02); and results at follow-up RR 0.90 (95% CI 0.76-1.07). REVIEWERS' CONCLUSIONS: The present evidence suggests that adding any psychosocial support to Standard MMT significantly improves the non-use of heroin during treatment. Retention in treatment and results at follow-up are also improved, although this findings did not achieve statistical significance. Insufficient evidence is available on other possible relevant outcomes such as Psychiatric symptoms/psychological distress, Quality of life. Limitations to this review are imposed by the heterogeneity of the trials both in the interventions and the assessment of outcomes. Results of studies were sometimes in disagreement and because of lack of detailed information no meta analysis could be performed to analyse the results related to the outcomes more often reported as positive results in the single studies. Duration of the studies was also too short to analyse other relevant outcomes such as mortality. In order to study the possible added value of any psychosocial treatment over an already effective treatment such as standard MMT, only big multi-site studies could be considered which define experimental interventions and outcomes in the most standardized way as possible.

Combined Modality Therapy↗

Outcomes of treatment of socially rehabilitated methadone maintenance patients in physicians' offices (medical maintenance): follow-up at three and a half to nine and a fourth years.

OBJECTIVE: To determine whether selected socially rehabilitated former heroin addicts maintained on methadone can continue successful rehabilitation while maintained on methadone by primary care physicians rather than licensed clinics. This procedure has been termed "medical maintenance." DESIGN: Cohort study with 42-111 months of follow-up. SETTING: Offices of hospital staff physicians (internists or family practitioners). PATIENTS: The 100 patients met extensive entry criteria, including five or more years in conventional methadone maintenance treatment; stable employment or other productive activity; verifiable financial support; and no criminal involvement, use of illegal drugs, or excessive alcohol use within three or more years. MEASUREMENTS AND MAIN RESULTS: Outcome measures used were retention in treatment, discharge for one of several reasons, lost medication incidents, and substance abuse. At one, two, and three years of treatment, 98, 95, and 85 patients, respectively, remained in medical maintenance. Cumulative proportional survival in treatment was 0.735 +/- 0.048 at five years and 0.562 +/- 0.084 at nine years. After 42-111 months, 72 patients remained in good standing; 15 patients had unfavorable discharges (11 for cocaine use, three for misuse of medication, and one for administrative violations); seven voluntarily withdrew from methadone in good standing (after receiving it for 9.1-24.4 years); four died; one transferred to a chronic care facility; and one voluntarily left the program. CONCLUSIONS: Carefully selected methadone maintenance patients in medical maintenance have a high retention rate and a low incidence of substance abuse and lost medication. Voluntary withdrawal from methadone maintenance after one or two decades is possible. The authors believe that medical maintenance should be made available to appropriate patients in other localities.

Adult↗

Comparison of 2 maintenance doses (100 microg vs 200 microg) in Hymenoptera venom immunotherapy: influence of the maintenance dose on the immunologic response.

BACKGROUND: In Hymenoptera venom immunotherapy, the maintenance dose is usually 100 microg. However, persistent systemic reactions to sting challenges could be treated by an increase in the maintenance dose to 200 microg with success, suggesting greater efficiency. OBJECTIVE: To compare the effects of 2 monthly maintenance doses (100 microg vs 200 microg) on skin test sensitivity and venom specific IgE antibody levels. METHODS: Twenty-two patients receiving Vespula venom immunotherapy were enrolled in this retrospective study. After rush therapy, the 100-microg maintenance dose initially administered was maintained (group 1, n = 13) or was increased to 200 microg (group 2, n = 9). RESULTS: Levels of venom specific IgE antibody and skin test results measured before the onset of immunotherapy were comparable in both groups. Unlike in group 1, a maintenance dose of 200 microg resulted in significant decreases in venom specific IgE antibody levels and skin test sensitivity. CONCLUSIONS: Increasing the monthly maintenance dose to 200 microg results in a greater degree of change in venom specific IgE antibody levels and skin test sensitivity than when maintaining a 100-microg dose. Our data strengthen those of previous clinical studies showing the usefulness of a 200-microg maintenance dose in the case of clinical failure of a 100-microg dose.

Adult↗

A randomized trial of maintenance versus no maintenance melphalan and prednisone in responding multiple myeloma patients.

In order to assess the role of maintenance melphalan and prednisone (MP) in responding multiple myeloma patients, 185 eligible patients who responded to initial MP with stabilization for at least 4 months were randomized to either stop treatment and resume therapy at relapse or to continue MP until relapse. Time to first relapse was significantly shorter in the no maintenance group (P = 0.0011), however 57% of the no maintenance patients had a second response when MP was restarted and others had minor improvement. The time to final progression on MP, which reflects the duration of disease control by MP, was therefore longer for the no maintenance group (median = 39 months) compared to the maintenance group (median = 31 months) although the observed difference was not statistically significant (P = 0.086). Median survival from start of MP in the maintenance group (46 months) was also not significantly different than the no maintenance group (51 months) (P = 0.587). Multifactor analysis of the randomized patients demonstrated shorter total remission duration and shorter survival in patients who had an initially rapid response to therapy or a lesser reduction in serum M-protein concentration.

Antineoplastic Combined Chemotherapy Protocols↗

[Energy maintenance requirements and energy requirement for protein retention in growing rats and broilers. 1. Energy maintenance requirements of growing rats].

In 4 experiments with 3 times 3 male Wistar rats each, which received rations with different protein contents (10; 25 and 40% crude protein in the dry matter), in the growth range between approximately 65 and 180 g live weight and with an environmental temperature of 30 degrees C, a total of 226 measurings of the total metabolism were carried out on the energy level maintenance, partly also with the insertion of a fasting day. The most important results were: On the energy level maintenance with the simultaneous catabolisation of body fat there was considerable protein energy retention, which amounted to between 30 and 40% of the retention achieved in the growth periods. The energy maintenance requirement can be determined with good reproducibility (standard mean deviation: +/-6%). The average energy requirement directly measured at the feeding level maintenance of 437 kJ metabolizable energy (ME)/kg live weight 0,75.d (n=224) differs insignificantly from the average value obtained by means of multiple regression analysis from experiment periods with feeding for growth 423 kJ ME/kg live weight 0,75.d (n=437). Consequently it is not necessary to differentiate between energy requirement for maintenance and energy requirement connected correlatively with the live weight (metabolic weight of the body) under conditions of growth. Energy maintenance requirement proved to be insignificantly dependent on the amount of protein in the feed. The relative values of protein quotas of 10, 25 and 40% in the feed were 100, 101 and 103%; the expected values (derived from the efficiency of ATP synthesis in the oxidation of carbohydrates and protein) amount of 100, 104 and 109%. The problem of the thermogenous effect of protein, which is also of great importance to human nutrition urgently requires further experimental investigation. For growing rats the best adaptation of the energy maintenance over the investigated period of development is achieved if the 2/3 potence of the live weight is chosen as the expression of the metabolic body weight. With high probability this can also be transferred to the characterisation of protein metabolisation.

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