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PubMed1995

Neuroprotection by N-methyl-D-aspartate antagonists in focal cerebral ischemia is dependent on continued maintenance dosing.

While N-methyl-D-aspartate antagonists have been shown to attenuate neuronal damage in focal cerebral ischemia, few studies have examined whether continuous or multiple dose treatment is necessary for maximum efficacy. We studied the effect of a loading dose only or load plus maintenance infusion using several non-competitive N-methyl-D-aspartate antagonists (dextromethorphan, dextrorphan, MK-801) and the levorotatory enantiomer of dextromethorphan (levomethorphan) in a rabbit model of focal cerebral ischemia. Forty-seven anesthetized rabbits underwent occlusion of the left internal carotid, anterior cerebral and middle cerebral arteries for 2 h followed by 4 h of reperfusion. Drugs were administered 10 min after occlusion. Dextromethorphan and dextrorphan protected against ischemic edema only when given as load plus maintenance (29% and 31% reduction, respectively), while both load only and load plus maintenance of MK-801 protected against edema (26% and 31% reduction, respectively). Levomethorphan load plus maintenance also protected against ischemic edema (25% reduction). However, dextromethorphan and dextrorphan both required maintenance infusion to protect against ischemic neuronal damage (24% and 27% reduction in area of ischemic neuronal damage, respectively), while levomethorphan failed to protect against neuronal injury even when given as load plus maintenance. Administration of MK-801 as load plus maintenance reduced ischemic neuronal damage by 23%, but this difference was not quite statistically significant. These results suggest that processes of ischemic damage, such as excitotoxic injury, continue for several hours beyond the initial period of focal ischemia, and that non-competitive N-methyl-D-aspartate antagonists require more prolonged administration to achieve neuroprotection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Involvement of alpha4 integrins in maintenance of cardiac sympathetic axons.

Sympathetic neurons extend and maintain axons that innervate the myocardium, and proper innervation is important for cardiac function. However, the molecular basis for axon outgrowth and maintenance is not well understood. We have shown previously that the integrin alpha4beta1 is expressed on developing axons, and the alpha4 function is important for the development of innervation in vivo [Wingerd, K.L., Goodman, N.L., Tresser, J.W., Smail, M.M., Leu, S.T., Rohan, S.J., Pring, J.L., Jackson, D.Y., and Clegg, D.O., 2002. Alpha 4 integrins and vascular cell adhesion molecule-1 play a role in sympathetic innervation of the heart. J. Neurosci. 22,10772-10780]. Here we examine the function of alpha4beta1 integrins in the maintenance of cardiac sympathetic innervation in vitro and in vivo, and investigate integrin expression and function after myocardial infarction and in hypertensive rats. On substrates of vascular cell adhesion molecule-1 (VCAM-1), alpha4beta1 was required for both initial outgrowth and maintenance of neurites in vitro. On fibronectin substrates, initial outgrowth requires only alpha4 integrins, but maintenance requires both alpha4 integrins and RGD-dependent integrins. In vivo, in adult Long Evans rats, inhibition of alpha4 integrins resulted in decreased maintenance of sympathetic fibers innervating the apex of the heart. However, alpha4 integrins were not detected on most sympathetic axons that sprout after myocardial infarction, and alpha4 function was not required for sprouting. Spontaneously hypertensive rats (SHR) have increased numbers of cardiac sympathetic fibers compared to the parental Wistar strain, but many of these lack alpha4 expression, and alpha4 function is not required for maintenance of these fibers in the heart. These results suggest that developing sympathetic axons and sprouting sympathetic axons use different mechanisms of outgrowth, and that maintenance of cardiac sympathetic innervation involves alpha4 integrins in some rat strains.

Adrenergic Fibers↗
PubMed1999

Efficacy of maintenance therapy after acute tocolysis: a meta-analysis.

OBJECTIVE: Our purpose was to analyze published randomized trials assessing the efficacy of maintenance tocolytic therapy after short-term tocolysis in patients with acute preterm labor. STUDY DESIGN: We supplemented a search of entries in electronic databases with references cited in original studies and review articles to identify randomized trials assessing the efficacy of maintenance tocolytic therapy after resolution of the acute preterm labor episode. Two masked investigators performed independent trial quality evaluation and data abstraction of each trial. We calculated an estimate of the odds ratio and risk difference for dichotomous outcomes, using both a random- and fixed-effects model. Continuous outcomes were pooled with a variance-weighted average of the within-study difference in means. RESULTS: Of 17 studies identified, 12 met our criteria for meta-analysis. These 12 trials included 1590 patients, including 855 who received maintenance tocolysis and 735 comparison patients who received placebo or no maintenance treatment. Compared with placebo or no treatment, the pooled odds ratio for preventing preterm delivery was 0.95 (95% confidence interval, 0. 77-1.17), and the odds ratio for preventing recurrent preterm labor was 0.81 (95% confidence interval, 0.64-1.03). In addition, use of maintenance tocolytic therapy was not associated with decreased rates of neonatal respiratory distress syndrome, perinatal deaths, or differences in birth weight. Although no difference was noted in mean gestational age at delivery, those receiving tocolytic agents had a longer latency period. CONCLUSION: Maintenance tocolytic therapy after successful treatment of an acute episode of preterm labor does not reduce the incidence of recurrent preterm labor or preterm delivery and does not improve perinatal outcome. Accordingly, the results of this meta-analysis do not support the use of maintenance tocolytic therapy after successful treatment of preterm labor.

Female↗
PubMed2000

The concept of maintenance physiotherapy.

This paper explores the concept of maintenance physiotherapy. Firstly, a consensus definition of maintenance physiotherapy is proposed following consultation with 11 senior physiotherapists throughout Australasia. This consensus definition is compared retrospectively with a definition of maintenance physiotherapy given in response to interview of 91 physiotherapists treating non-catastrophically injured motor vehicle patients more than five years post-accident (treating physiotherapists). Comparison was made by distilling the experts' definition into nine check points and scoring definitions given by the treating physiotherapists against these nine points. The results demonstrated a concurrence between the two groups of between zero and seven with a median of four. This paper supports maintenance physiotherapy as an accepted treatment form. To adhere more closely to the consensus definition of maintenance physiotherapy, treating physiotherapists should consider referral to non-physiotherapy alternatives, to ensure all possible treatment options are exhausted before the rehabilitation phase is complete. In addition, current objective outcome measures to justify and measure continued treatment should be used regularly. Patient education, consistent clinical diagnosis and categorisation of long-term patient groups should be more fully incorporated into the practice of maintenance physiotherapy. The paper aims to provide a reference from which the concept of maintenance physiotherapy can evolve.

Journal Article↗
PubMed1990

Normalization of plasma arginine vasopressin concentrations when children with meningitis are given maintenance plus replacement fluid therapy.

We hypothesized that plasma arginine vasopressin (AVP) concentrations in children with meningitis are appropriate for the children's degree of hypovolemia, even though the concentrations were higher than expected for the serum osmolality. A randomized study was conducted to compare the effect on plasma AVP concentrations of giving maintenance fluid requirements plus replacement of any deficit versus restricting fluids to two thirds of maintenance requirements for 24 hours. Plasma AVP concentrations and serum osmolality were measured before fluid therapy was begun and again after 24 hours. Nineteen children, 2 months to 17 years of age, were studied; 13 had bacterial meningitis (12 with Haemophilus influenzae type b). Ten children (seven with bacterial meningitis) received a mean of 1.42 times the calculated maintenance fluid requirements, and nine (six with bacterial meningitis) were restricted to a mean of 0.65 times maintenance. Children in the maintenance group also received significantly more sodium (mean = 6.3 mEq/kg/24 hr) than children in the fluid-restricted group (mean = 2.0 mEq/kg/24 hr). The two groups were comparable for plasma AVP concentration and serum osmolality before fluid therapy was begun. The plasma AVP concentration was significantly lower after 24 hours of maintenance plus replacement fluids than after fluid restriction (p = 0.005), and the change in AVP concentration correlated with the amount of sodium given (p less than 0.02). This study supports the hypothesis that serum AVP concentrations are elevated in patients with meningitis because of hypovolemia and become normal when sufficient sodium is given to facilitate reabsorption of water by the proximal tubule of the kidney. Patients with meningitis can be given maintenance plus replacement fluids but should be monitored for the development of the syndrome of inappropriate secretion of antidiuretic hormone.

Adolescent↗
PubMed1982

Adjuvant vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum chemotherapy regimen with and without maintenance in patients with resected stage IIB testis cancer.

A total of 42 patients with stage IIB nonseminomatous germ cell tumors of the testis after orchiectomy and retroperitoneal lymph node dissection received adjuvant chemotherapy with the modified vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum regimen. Of the patients 29 had N2B and 13 had N3 nodal categories. Adjuvant vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum chemotherapy was given with maintenance in the first 24 patients and without maintenance (2 months of chemotherapy) in the subsequent 18. Chemotherapy with maintenance was given for 1 year and began with 2 inductions 3 to 4 weeks apart: 600 mg./m.2 intravenous cyclophosphamide, 30 mg. intravenous bleomycin, 1 mg./m.2 intravenous actinomycin D and 4 mg./m.2 intravenous vinblastine on day 1, 20 mg./m.2 bleomycin daily by continuous 24-hour induction on days 1 to 3 and 120 mg./m.2 intravenous cis-platinum with mannitol-induced diuresis on day 4. Maintenance with 6 mg./m.2 intravenous vinblastine and 1 mg./m.2 intravenous actinomycin D every 3 weeks was initiated 3 weeks after the second induction for the remainder of the year. Adjuvant vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum chemotherapy without maintenance was given for 2 months and used 3 inductions identical to those described previously. Complete remission has been maintained in 41 of 42 patients: all 24 who received maintenance chemotherapy and 17 of 18 who did not. One patient had a relapse with sarcoma and 6 required broad-spectrum antibiotics for fever during myelosuppression. A temporary increase in the serum creatinine of more than 2 mg. per cent occurred in 1 patient. Chronic renal failure or pulmonary fibrosis was not seen. Our results show that vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum chemotherapy is effective in the prevention of recurrences in patients with resected stage IIB disease, and suggest that adjuvant chemotherapy is equally effective with or without maintenance.

Adolescent↗
PubMed2001

Tolerability of bacille Calmette-Guérin maintenance therapy for superficial bladder cancer.

OBJECTIVES: To study the influence of adverse reactions on adherence to an immunotherapy maintenance schedule and the recurrence rate of bladder cancer. Bacille Calmette-Guérin immunotherapy has documented efficacy in the management of high-risk superficial bladder cancer. However, the optimal duration of intravesical bacille Calmette-Guérin therapy and the risk/benefit ratio of maintenance therapy are controversial. METHODS: From April 1996 to April 2000, 72 patients with superficial bladder cancer were treated with Immucyst (six consecutive weekly instillations of 81 mg) and then received maintenance therapy consisting of three consecutive weekly instillations 3, 6, 12, 18, 24, 30, and 36 months later. Adverse reactions, studied during 518 instillations, were classified in four categories using a scale based on the World Health Organization recommendations, and their impact on the adherence to therapy was analyzed. RESULTS: After an average follow-up of 24 months, a durable disease-free response was observed in 84.9% of the patients; 12.5% of patients had a relapse and 2.6% had disease progression. The response rate was similar in patients with and without adverse reactions. Only 14 patients (19%) received all the scheduled maintenance instillations. The dose was reduced in 41 patients (57%), and treatment was stopped in 28 patients (39%). In multivariate analysis, an adverse event score of 1.5 or greater during induction therapy was significantly associated with cessation or modification of maintenance therapy (P = 0.01). CONCLUSIONS: The scale developed in this study to monitor the adverse reactions to bacille Calmette-Guérin and their impact on the adherence to maintenance therapy may be helpful for tailoring maintenance regimens or implementing protective measures (dose reduction or treatment postponement).

Adjuvants, Immunologic↗
PubMed1996

Duration and intensity of maintenance chemotherapy in acute lymphoblastic leukaemia: overview of 42 trials involving 12 000 randomised children.

BACKGROUND: The effects on long-term outcome in childhood acute lymphoblastic leukaemia (ALL) of the duration and the intensity of maintenance chemotherapy need to be assessed reliably. With this objective the Childhood ALL Collaborative Group coordinated a worldwide overview of all randomised trials that began before 1987. METHODS: Individual patient data were sought for about 3900 children in trials of longer vs shorter maintenance (eg, 3 vs 2 years), 3700 in trials of intensive "reinduction" chemotherapy during maintenance, and 4400 in trials of various other questions, including 1300 in trials of pulses of vincristine and prednisone (VP) during maintenance. Analyses were of survival in first remission, overall survival, and cause-specific mortality. FINDINGS: Deaths during remission were increased by longer maintenance (2.7 percent vs 1.2 percent), VP pulses (4.0 vs 3.2 percent), and intensive reinduction (4.8 percent vs 3.3 percent), but these increases were counterbalanced by reductions in relapses. Total events (relapse or death) were significantly reduced by longer maintenance (23.3 percent vs 27.6 percent), VP pulses (31.2 percent vs 40.4 percent) and intensive reinduction (27.8 percent vs 35.8 percent) (each 2p<0.001). Many of those who relapsed were successfully re-treated, however, and only for intensive reinduction was overall survival significantly improved (18.5 percent vs 22.3 percent; 2p=0.01). INTERPRETATION: Intensive reinduction chemotherapy in these trials produced an absolute improvement of about 4 percent in long-term survival; if the extra deaths in remission had been avoided, this would have been a 5 percent benefit. Further improvements in survival seem more likely to be obtained with intensive treatment than with longer low-level maintenance.

Adolescent↗
PubMed2001

Outcomes after methadone maintenance and methadone reduction treatments: two-year follow-up results from the National Treatment Outcome Research Study.

This paper provides a detailed analysis of the 2-year outcomes for 351 drug misusers allocated on an intention-to-treat basis to methadone maintenance or methadone reduction treatments. Both groups showed substantial reductions in their use of illicit drugs and in other outcome areas. However, whereas most methadone maintenance patients received maintenance, only about one third of those allocated to methadone reduction received methadone reduction, and many actually received a form of methadone maintenance. Reduction patients were more likely to receive low doses of methadone, and were less likely to remain in treatment. For maintenance patients, higher doses and retention in treatment were both associated with improvements in illicit heroin use at 2 years. For the reduction patients, the more rapidly the methadone was reduced, the worse the heroin use outcomes. For patients in both treatment conditions, reductions in heroin use were associated with improvements in other outcome areas. The more severely dependent patients showed better outcomes in methadone maintenance. Methadone reduction treatment processes were associated with poor outcomes, and many patients who were allocated to methadone reduction treatment did not receive reduction treatment as intended. This calls into question the appropriateness of either the initial treatment planning process or the treatment delivery process, or both. A clearer distinction should be made between methadone maintenance and methadone reduction. Treatment goals should be made explicit both to the patient and to the clinical staff at the start of treatment. We suggest the need for a reappraisal of the goals and procedures of methadone reduction treatment.

Chi-Square Distribution↗
PubMed2002

Abstinence reinforcement maintenance contingency and one-year follow-up.

BACKGROUND: Relapse to drug use is often seen when contingencies designed to reduce drug use are discontinued. This paper reports on a stepdown maintenance contingency and 1-year follow-up in 110 patients who were maintained on methadone (50 or 70 mg/day) and who had completed a contingency management trial targeted to decreasing their opiate use. In the prior study (induction phase, 8 weeks) participants received vouchers for each opiate-negative urine screen or noncontingently. METHODS: In this study (maintenance phase, 12 weeks), participants were rerandomized to receive vouchers and take-home methadone doses contingent on providing opiate-negative urine specimens (N=55) or noncontingently (N=55). Since participants had been rerandomized from induction-phase contingencies, most study data were analyzed as if from a 2 x 2 (inductionxmaintenance) design. Follow-up interviews were conducted at 3, 6, and 12 months after study participation. RESULTS: Patients who received the maintenance contingency following an 8-week induction contingency had better outcomes than those who received noncontingent incentives in either the maintenance or induction phases of the trial. Good outcome at follow-up was predicted by enrollment in methadone maintenance after the study. Significantly more participants in the maintenance contingency group transferred directly to another methadone program. CONCLUSION: These findings support the therapeutic value of extending the duration of contingency management and long-term methadone maintenance.

Adult↗
PubMed2002

Effects of oral THC maintenance on smoked marijuana self-administration.

Studies have shown that the Delta(9)-tetrahydrocannabinol (Delta(9)-THC) concentration in marijuana cigarettes is an important factor for the maintenance of marijuana self-administration. Yet, the impact of oral Delta(9)-THC treatment on marijuana self-administration is unknown. Because other agonist therapies have been demonstrated to be effective for the treatment of substance use disorders, the objective of this study was to evaluate the influence of oral Delta(9)-THC maintenance on choice to self-administer smoked marijuana. During this 18-day residential study, 12 healthy research volunteers received one of three doses of oral Delta(9)-THC capsules (0, 10, 20 mg q.i.d.) for 3 consecutive days, followed by 3 consecutive days of matching placebo. The order of active Delta(9)-THC administration was counterbalanced. Each morning, except on days 6, 12, and 18, participants smoked the 'sample' marijuana cigarette (1.8% Delta(9)-THC w/w) and received a $2 voucher (redeemable for cash at study's end). Following the sample, volunteers participated in a four-trial choice procedure during which they had the opportunity to self-administer either the dose of marijuana they sampled that morning or to receive the $2 voucher. Relative to placebo Delta(9)-THC maintenance, participants' choice to self-administer marijuana was not significantly altered by either of the two active Delta(9)-THC maintenance conditions. Some 'positive' subjective drug-effect ratings following the sample marijuana cigarette were reduced: by day 3 of active oral Delta(9)-THC maintenance, participants' rating of 'Good Drug Effect' and 'High' were significantly decreased. Smoked marijuana-related total daily caloric intake was not significantly altered under any maintenance conditions. Finally, the effects of smoked marijuana on psychomotor task performance were only minimally affected by oral Delta(9)-THC maintenance. These data indicate that participants' choice to self-administer marijuana was unaltered by the oral Delta(9)-THC dosing regimen used in the present investigation.

Administration, Oral↗
PubMed2005

Post-treatment phone contact: a weight maintenance strategy in obese youngsters.

This study investigated the effect of post-treatment phone contact on weight-loss maintenance and activity behaviour in obese youngsters. In all, 20 patients who completed a weight reduction program were randomly assigned to a 5-month maintenance programme (experimental) or control condition. Following the maintenance programme, patients sent a weekly activity diary to the therapist, who in turn phoned them biweekly to discuss their activities. Body weight, stature and physical activity were measured before and after the maintenance programme. The control group showed a continuous increase in overweight after initial treatment, while the experimental group showed a steep increase during the summer holidays (no intervention), but this increase slowed down during the maintenance programme (P<0.05). Moderate-to-high intensity activities increased during the maintenance programme in the experimental group, but decreased in the control group (P<0.001). In conclusion, post-treatment phone contact appears to have the potential to be an effective maintenance strategy in obese youngsters.

Adolescent↗
PubMed2004

Transdermal nicotine maintenance attenuates the subjective and reinforcing effects of intravenous nicotine, but not cocaine or caffeine, in cigarette-smoking stimulant abusers.

The effects of transdermal nicotine maintenance on the subjective, reinforcing, and cardiovascular effects of intravenously administered cocaine, caffeine, and nicotine were examined using double-blind procedures in nine volunteers with histories of using tobacco, caffeine, and cocaine. Each participant was exposed to two chronic drug maintenance phases (21 mg/day nicotine transdermal patch and placebo transdermal patch). Within each drug phase, the participant received intravenous injections of placebo, cocaine (15 and 30 mg/70 kg), caffeine (200 and 400 mg/70 kg), and nicotine (1.0 and 2.0 mg/70 kg) in mixed order across days. Subjective and cardiovascular data were collected before and repeatedly after drug or placebo injection. Reinforcing effects were also assessed after each injection with a Drug vs Money Multiple-Choice Form. Intravenous cocaine produced robust dose-related increases in subjective and reinforcing effects; these effects were not altered by nicotine maintenance. Intravenous caffeine produced elevations on several subjective ratings; nicotine maintenance did not affect these ratings. Under the placebo maintenance condition, intravenous nicotine produced robust dose-related subjective effects, with maximal increases similar to the high dose of cocaine; nicotine maintenance significantly decreased the subjective and reinforcing effects of intravenous nicotine. The results of the present study demonstrate that chronic nicotine maintenance produces tolerance to the effects of intravenous nicotine, but does not affect the subjective or reinforcing effects of cocaine or caffeine.

Administration, Cutaneous↗
PubMed2005

Relationship of mania symptomatology to maintenance treatment response with divalproex, lithium, or placebo.

Euphoric and mixed (dysphoric) manic symptoms have different response patterns to divalproex and lithium in acute mania treatment, but have not been studied in relationship to maintenance treatment outcomes. We examined the impact of initial euphoric or dysphoric manic symptomatology on maintenance outcome. Randomized maintenance treatment with divalproex, lithium, or placebo was provided for 372 bipolar I patients, who met improvement criteria during open phase treatment for an index manic episode. The current analysis grouped patients according to the index manic episode subtype (euphoric or dysphoric), and evaluated the impact on maintenance treatment outcome. The rate of early discontinuation due to intolerance during maintenance treatment was higher for initially dysphoric patients (N=249) than euphoric patients (N=123; 15.7 vs 7.3%, respectively; p=0.032). Both lithium (23.2%) and divalproex (17.1%) were associated with more premature discontinuations due to intolerance than placebo (4.8%; p=0.003 and 0.02, respectively) in the initially dysphoric patients. Among initially euphoric patients, treatment with lithium was associated with significantly more premature discontinuations due to intolerance compared to placebo (18.2 vs 0%; p=0.03), and divalproex was significantly (p=0.05) more effective than lithium, but not placebo in delaying time to a depressive episode. Initial euphoric mania appeared to predispose to better outcomes on indices of depression and overall function with divalproex maintenance than with either placebo or lithium. Dysphoric mania appeared to predispose patients to more side effects when treated with either divalproex or lithium during maintenance therapy.

Adult↗
PubMed2005

Effects of high-dose methadone maintenance on cocaine place conditioning, cocaine self-administration, and mu-opioid receptor mRNA expression in the rat brain.

Methadone maintenance at appropriate doses can effectively reduce cocaine abuse in heroin-dependent individuals. In the present studies, we investigated the effect of high-dose methadone maintenance cocaine conditioned place preference (CPP) and cocaine intravenous self-administration. Rats implanted with methadone-filled osmotic mini-pumps (20 and 55 mg/kg/day, SC) and conditioned with cocaine (1, 5, and 20 mg/kg, i.p.) did not express cocaine CPP. Similarly, rats implanted with methadone pumps (55 mg/kg/day) after cocaine conditioning (20 mg/kg) displayed neither spontaneous nor cocaine-precipitated (20 mg/kg, i.p.) CPP. In contrast, methadone maintenance (30 and 55 mg/kg/day, SC) did not alter the intravenous self-administration (continuous schedule of reinforcement) of various doses of cocaine (0.1, 0.5, and 2.0 mg/kg/inf). To explore neuropharmacological interactions between methadone maintenance and cocaine conditioning, we quantitatively measured mRNA levels of mu-opioid receptor (MOR) and proopiomelanocortin genes 10 days after methadone maintenance. MOR mRNA levels in both the nucleus accumbens core and frontal cortex were significantly elevated in rats exposed to cocaine during CPP conditioning. However, upregulation of MOR mRNA levels in the nucleus accumbens core were reduced by methadone maintenance in a dose-dependent manner. In conclusion, our results suggest that high-dose methadone maintenance does not alter the direct reinforcing effect of cocaine, but blocks spontaneous and cocaine-precipitated cocaine-seeking, possibly by preventing MOR alterations in the nucleus accumbens core induced by cocaine conditioning.

Analysis of Variance↗
PubMed2000

Randomized trial of supervised injectable versus oral methadone maintenance: report of feasibility and 6-month outcome.

AIM: To assess the feasibility of a randomized clinical trial of supervised injectable versus oral methadone maintenance and to assess medium-term treatment outcomes. DESIGN: Randomized clinical trial of supervised injectable versus supervised oral methadone maintenance treatment (MMT). Trial participants were dependent illicit opiate injectors allocated at intake to supervised injectable or oral methadone maintenance treatment. SETTING: Specialist addictions treatment centre in South London. SUBJECTS: Forty dependent illicit opiate injectors seeking methadone maintenance treatment. INTERVENTIONS: Daily supervised injectable and oral methadone maintenance, delivered at the treatment centre. MAIN OUTCOME MEASURES: Frequency of illicit heroin use and frequency of illicit drug injecting during 30 days before intake to treatment and prior to 6-month follow-up. SECONDARY OUTCOME MEASURES: frequency of use of illicit methadone, crack cocaine, benzodiazepines and alcohol, physical and psychological health symptoms and acquisitive crime. RESULTS: Injectable and oral MMT were both generally acceptable to the study participants: there was a high level of agreement to enter the randomized trial, and subsequent retention in treatment was good. The average number of days of illicit heroin use reduced from 22.2 to 7.6 for the injectable MMT group and from 22.4 to 8.7 for the oral MMT group. The average number of days of illicit injecting reduced from 25.7 to 10.8 days for the injectable group and from 20.1 to 11.9 days for the oral group. Patients' physical and psychological health symptoms and involvement in acquisitive crime also reduced in both groups. Treatment satisfaction ratings at follow-up were higher among patients in the injectable MMT group. The ratio for the actual medication costs between injectable and oral MMT was 6.8:1, and for the direct operational costs was 4.7:1. There was some evidence of a differential patient response with greater reductions in heroin use occurring among patients who were daily illicit injectors and had poorer psychological and physical health (at entry) who were allocated to injectable MMT. CONCLUSIONS: Conduct of the trial has demonstrated that it is feasible to implement supervised injectable methadone maintenance treatment in the context of (although separate from) a specialist oral methadone maintenance service. Patients assigned to receive either supervised injectable or oral MMT had broadly equivalent, positive during-treatment outcomes at 6-month follow-up. Future studies should seek to identify patient characteristics which are linked to good outcome in injectable MMT. Practical evidence-based guidance to physicians about determining which patients are more suitable for injectable MMT is urgently needed.

Administration, Oral↗
PubMed2001

Effective maintenance leukocytapheresis for patients with steroid dependent or resistant ulcerative colitis.

We prospectively examined the effect of leukocytapheresis (LA) on the maintenance of remission in 7 patients with ulcerative colitis (UC) who were initially refractory to corticosteroid therapy (steroid resistant or steroid dependent). The patients with refractory UC had been in remission due to LA (induction LA) in combination with the steroid therapy. They were then treated with LA once or twice a month for the purpose of maintaining remission (maintenance LA). The maintenance LA was performed by either a centrifuge method in 5 patients or a polyester adsorbent column method in 2 patients. Steroid dosage was gradually tapered as little as possible without recurrence based on clinical and/or colonoscopical judgments. Four patients were maintained in remission without steroids over 12 months. Recurrence was observed in 3 patients at 3, 3, and 6 months after the beginning of the maintenance LA, respectively. Two of the 3 patients were again conducted to remission by the second induction LA and maintained in remission by the second maintenance LA. Two patients finally underwent total colectomy because of recurrence of UC in a severe form. It is concluded that the maintenance LA therapy might be effective in some patients with steroid dependent or resistant UC for the maintenance of remission without steroids.

Adolescent↗
PubMed2003

First-line and maintenance treatment with rituximab for patients with indolent non-Hodgkin's lymphoma.

The chimeric human-mouse anti-CD20 monoclonal antibody rituximab has durable single-agent activity in patients with relapsed and refractory indolent non-Hodgkin's lymphoma. The focus of this report is a phase II trial evaluating the efficacy of single-agent rituximab as first-line therapy in patients with indolent lymphoma and scheduled maintenance treatment in prolonging duration of remission. Patients received a 4-week course of standard rituximab (375 mg/m(2) intravenously weekly x 4). Those achieving objective response or stable disease then received maintenance courses of standard rituximab every 6 months, for a maximum of four rituximab courses. Of 62 patients entered in the trial, 61% had follicular lymphoma while 39% had small lymphocytic lymphoma (SLL). At 6 weeks, 28 of 60 evaluable patients (47%) had an objective response. The response rate improved to 73% (37% complete response) following maintenance rituximab therapy and was similar in patients with follicular lymphoma and SLL (76% v 70%, respectively). Median progression-free survival for the entire group was 34 months. Single-agent therapy was well tolerated and maintenance rituximab was administered without grade 3/4 toxicity. Because of the higher activity of rituximab in this study compared with previous results in patients with relapsed or refractory SLL, a second phase II trial of identical design but limited to patients with SLL and chronic lymphocytic leukemia was initiated. Forty-four patients entered this second trial and, at present, 27 continue to receive maintenance courses of rituximab. The current response rate is 56% (8% complete responses). In summary, rituximab appears highly active as first-line single-agent therapy for indolent non-Hodgkin's lymphoma and responses may be improved with maintenance courses of rituximab. Results suggest a higher response rate to rituximab when used as first-line compared with second/third-line treatment, particularly in the subset of patients with SLL and chronic lymphocytic leukemia. Further follow-up will provide important information regarding the impact of first-line and maintenance rituximab on progression-free survival in patients with indolent non-Hodgkin's lymphoma.

Antibodies, Monoclonal↗