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PubMed2002

Association between pulse pressure and mortality in patients undergoing maintenance hemodialysis.

CONTEXT: Although increased blood pressure is associated with adverse outcomes in the general population, elevated blood pressure is associated with decreased mortality in patients with end-stage renal disease undergoing maintenance hemodialysis. Recent investigations in the general population have demonstrated the predictive utility of pulse pressure (systolic minus diastolic blood pressure), a measure reflecting the pulsatile nature of the cardiac cycle. OBJECTIVES: To estimate the relationship between pulse pressure and mortality in patients undergoing maintenance hemodialysis and to test our hypothesis that an increasing pulse pressure would be associated with increased risk of death up to 1 year despite the inverse relationship between conventional blood pressure measures and mortality in patients with end-stage renal disease. DESIGN, SETTING, AND PATIENTS: Retrospective cohort investigation of patients with end-stage renal disease undergoing maintenance hemodialysis at 782 hemodialysis facilities throughout the United States. Of 44 069 eligible patients as of January 1, 1998, 37 069 with complete demographic data were included in the analyses of clinical and laboratory data collected from October 1 through December 31, 1997. Patients were followed up through December 31, 1998. MAIN OUTCOME MEASURES: The primary study outcome was death at 1 year. A secondary outcome was the magnitude of the pulse pressure. RESULTS: The final patient cohort was similar to national averages with respect to age, sex, race, and diabetic status. Mean (SD) pulse pressures before dialysis were 75.0 (15.0) mm Hg and 66.9 (13.9) mm Hg after dialysis. By the end of the 1-year follow-up, 5731 patients (18.4%) died. After adjusting for level of systolic blood pressure, multivariable Cox proportional hazards modeling showed a direct and consistent relationship between increasing pulse pressure and increasing death risk. Each incremental elevation of 10 mm Hg in postdialysis pulse pressure was associated with a 12% increase in the hazard for death (hazard ratio, 1.12; 95% confidence interval, 1.06-1.18). Postdialysis systolic blood pressure was inversely related to mortality with a 13% decreased hazard for death for each incremental elevation of 10 mm Hg (hazard ratio, 0.87; 95% confidence interval, 0.84-0.90). In a multivariable linear regression model, important variables directly associated with elevated pulse pressure included age, diabetes, white race, female sex, and number of years receiving dialysis (all P<.001). CONCLUSIONS: Pulse pressure is associated with risk of death in a large, nationally representative sample of patients undergoing maintenance hemodialysis. The recognition of pulse pressure as an important correlate of mortality in patients receiving dialysis highlights the need to investigate the relationship between potential therapeutic implications of conduit vessel function and clinical outcomes in patients with end-stage renal disease.

Age Factors↗
PubMed2006

Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy after sustained virologic suppression.

CONTEXT: The long-term adverse effects, expense, and difficulty of adherence to antiretroviral regimens have led to studies of simpler maintenance therapies. Maintenance therapy with ritonavir-boosted atazanavir alone is a possible option because of low pill burden, once-daily dosing, safety, and unique resistance profile. OBJECTIVE: To assess whether simplified maintenance therapy with atazanavir-ritonavir alone after virologic suppression increases the risk of virologic failure (2 consecutive human immunodeficiency virus type 1 [HIV-1] RNA measurements of > or =200 copies/mL). DESIGN, SETTING, AND PARTICIPANTS: Single-group, open-label, multicenter, 24-week pilot study of 36 HIV-infected adults with virologic suppression for 48 weeks or longer receiving their first protease inhibitor (PI)-based regimen. The study was conducted between September 1, 2004, and April 18, 2006, at 12 participating AIDS clinical trial units in the United States. INTERVENTION: Participants switched PIs to atazanavir-ritonavir at entry and discontinued nucleoside analog reverse transcriptase inhibitors (NRTIs) after 6 weeks. MAIN OUTCOME MEASURES: Virologic failure within 24 weeks of discontinuing NRTIs. Other measures included HIV-1 drug resistance, plasma atazanavir concentrations, adverse events, CD4 cell counts, plasma lipid levels, and HIV-1 RNA levels in seminal plasma. RESULTS: Thirty-six participants enrolled and 2 discontinued before simplification to atazanavir-ritonavir alone. Thirty-four patients were included in the analysis of the primary end point after 24 weeks: 1 withdrew voluntarily, and 33 continued the regimen. Virologic success (absence of failure) through 24 weeks of simplified therapy occurred in 91% (31 of 34 patients; lower 90% confidence interval limit = 85%). Three participants experienced virologic failure 12, 14, and 20 weeks after simplification, with plasma HIV-1 RNA levels of 4730, 1285, and 28 397 copies/mL, respectively. Resistance testing at failure did not identify PI resistance mutations. Plasma atazanavir concentrations at failure were low or below detection in 2 of 3 participants experiencing failure. There were no treatment discontinuations for adverse events after simplification; no significant changes in CD4 cell counts or plasma lipid levels; and no detectable HIV-1 RNA in seminal plasma from all 8 participants tested. CONCLUSIONS: These preliminary data suggest that simplified maintenance therapy with atazanavir-ritonavir alone may be efficacious for maintaining virologic suppression in carefully selected patients with HIV infection. These findings require confirmation in larger, randomized trials of this strategy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00084019.

Adult↗
PubMed1996

Synapse restructuring associated with the maintenance phase of hippocampal long-term potentiation.

Synapses in the middle molecular layer of the rat dentate gyrus were analyzed by electron microscopy during the maintenance phase of long-term potentiation (LTP). LTP was induced by high-frequency stimulation of the medial perforant path carried out on each of 4 consecutive days. The dentate gyrus was examined electron microscopically 13 days following the fourth stimulation. At this time point, synaptic responses were still significantly enhanced relative to baseline, although the extent of their potentiation was lower than 1 hour after the last high-frequency stimulation. Stimulated, but not potentiated, rats served as controls. Using the stereological double disector method, estimates of the number of different morphological types of synapses per postsynaptic neuron were obtained. The number of asymmetrical axodendritic synapses increased (by 28%) during LTP maintenance, whereas the number of other synaptic types was not significantly altered. Our previous work demonstrated that the induction of LTP is followed by a selective increase in the number of axospinous perforated synapses with multiple, completely partitioned, transmission zones. Thus, the induction and maintenance phases of LTP are characterized by different structural synaptic alterations. These alterations may be related to each other as indicated by another finding of the present study regarding the existence of perforated synapses that appear to be transitional between axospinous and axodendritic junctions. This suggests a model of structural synaptic plasticity associated with LTP in which some axospinous perforated synapses increase in numbers shortly after the induction of LTP and are then converted into axodendritic ones during LTP maintenance.

Animals↗
PubMed1998

Formation and maintenance of the myelin sheath in the peripheral nerve: roles of cell adhesion molecules and the gap junction protein connexin 32.

Based on previous in vitro studies, the cell adhesion molecules L1, N-CAM, MAG, and P0, which all belong to the immunoglobulin (Ig)-superfamily, have been suggested to mediate myelin formation in the peripheral nervous system. Unexpectedly, studies in mice deficient for the corresponding molecules revealed that only P0 plays pivotal roles during the formation of peripheral nerve myelin in vivo, while L1-, N-CAM-, and MAG-deficient mice develop myelin of normal ultrastructure. However, MAG turned out to be important for the maintenance of myelin, as reflected by degeneration of myelin and axons in MAG-deficient mice older than 6 months. The MAG-mediated maintenance of myelin is backed up by N-CAM, since mice deficient in both MAG and N-CAM show an earlier and more prominent myelin degeneration than MAG single mutants. Another peripheral nerve component involved in the maintenance of myelinated fibers is connexin 32 (Cx32), a gap junction channel protein that does not belong to the Ig-superfamily. Mice deficient in Cx32 initially form normal myelin, which then develops blown-up periaxonal collars and abnormally shaped non-compacted regions followed by myelin and axonal degeneration. Our findings strongly support the view that very few myelin components are necessary for myelin formation whereas the maintenance of myelin is much more sensitive to molecular alterations. In addition, it became evident that myelin molecules can fulfill functionally overlapping roles that ensure that myelination takes place even under conditions in which there is a deficiency in the normal molecular components of myelin.

Animals↗
PubMed2000

Randomized trial of alpha-interferon or dexamethasone as maintenance treatment for multiple myeloma.

In order to assess the role of alpha-interferon or dexamethasone as maintenance therapy for multiple myeloma, 172 consecutive, previously untreated patients with disease of low or intermediate tumor mass received primary therapy with oral melphalan and intermittent, high-dose dexamethasone (MD), repeated monthly. Within 5 months, 84 responding patients were assigned at random to maintenance treatment with alpha-interferon (3 mU s.c. 3 x weekly) or dexamethasone (20 mg/m2 p.o. each morning for 4 days) repeated monthly until relapse. Upon relapse, MD was resumed for 2 cycles and second responses were maintained with 4-day courses of melphalan-dexamethasone until second relapse. Initial response was achieved in 88 patients (51%) after a median 0.7 month and no more than 3 courses of MD, a frequency of response similar to that observed previously with dexamethasone alone. There were identical median remissions of 10 months with interferon or dexamethasone, both maintenance regimens being associated with infrequent, mild, and reversible side effects. Significantly more patients responded again to resumption of MD after disease relapse to interferon (82%) than to dexamethasone (44%) (P = 0.001). The median remission from randomization to melphalan-resistant second relapse was 32 months for patients maintained initially on interferon compared to 19 months for those on dexamethasone (P = 0.01). These findings supported an advantage for interferon in remission maintenance by increasing the frequency of tumor recontrol with later treatment that included dexamethasone.

Adult↗
PubMed1985

Comparison of maintenance treatment regimens for first central nervous system relapse in children with acute lymphocytic leukemia. A Pediatric Oncology Group study.

Eighty-seven children with central nervous system (CNS) leukemia were randomized to receive either induction intrathecal chemotherapy (ITC) and cranial irradiation (CRT) plus maintenance ITC, or induction ITC and craniospinal irradiation (CSpRT) with no maintenance ITC. ITC consisted of six weekly injections of methotrexate, hydrocortisone, and arabinosylcytosine. Also, intensification of systemic induction and maintenance chemotherapy was given. CRT + ITC was given as CRT, 2400 rad in 12 fractions followed by ITC maintenance bimonthly for 2 years. Craniospinal irradiation consisted of CRT + 1400 rad in ten fractions to the spine. Randomization was stratified according to whether CNS leukemia occurred at initial diagnosis of acute lymphocytic leukemia (ALL) (Stratum I, 15 patients), during first bone marrow (BM) remission (Stratum II, 49 patients), simultaneous with first BM relapse (Stratum III, 12 patients), or during second BM remission (Stratum IV, 11 patients). The median follow-up for patients who remain at risk is 15 + months. Eight children (seven on CRT + ITC, one on CSpRT) developed presumed therapy related encephalopathy. In Stratum II, 16 of 29 (55%) patients receiving CRT + ITC experienced adverse events: 3 deaths during continuous complete remission (CCR) and 13 relapses (2 CNS, 1 CNS + BM, 1 BM + testes, and 2 testes) as compared with only 5 relapses in 20 (25%) patients on CSpRT (1 CNS, 1 CNS + BM, 1 BM, and 2 testes). The children on both regimens were comparable for sex, race, age at initial ALL diagnosis, time from ALL diagnosis to first episode of CNS leukemia, systemic therapy both before and after CNS relapse, and number of blasts in the spinal fluid at diagnosis of CNS leukemia. The conclusion is that children with isolated CNS leukemia can achieve prolonged survival with aggressive therapy, and that CSpRT is possibly less toxic and more likely than is CRT + ITC to prevent subsequent BM and testicular relapse (P less than 0.02), but not subsequent CNS relapse (P = 0.7). A possible systemic therapy effect of spinal irradiation is postulated to explain the superiority of CSpRT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Early intensification and short-term maintenance chemotherapy does not prolong survival in acute myelogenous leukemia.

Forty-one previously untreated patients with a diagnosis of acute myelogenous leukemia (AML) were entered on a study using early intensification followed by a short-term maintenance chemotherapy. Induction and early intensification consisted of three to four cycles of doxorubicin, vincristine, cytosine arabinoside (Ara-C) and prednisone (ADOAP) in escalating dosages. Maintenance therapy used three cycles of Ara-C thioguanine (AT), followed by three cycles of cyclophosphamide and rubidazone with vincristine and prednisone (CROP). Median total duration of therapy was 9 months. The overall complete remission (CR) rate was 73%. Tolerance to chemotherapy and dose escalation were better for patients who received their induction and early intensification in the protected environment. The overall median survival was 75 weeks. Compared to a historical control group treated with long-term maintenance chemotherapy, patients achieving CR on the current study had similar median remission (52 versus 65 weeks; P = 0.3) and survival durations (94 versus 98 weeks). This regimen using early intensification and short-term maintenance chemotherapy did not improve the overall prognosis of this AML population.

Adolescent↗
PubMed1991

Intensive chemotherapy induction followed by interferon-alpha maintenance in patients with Philadelphia chromosome-positive chronic myelogenous leukemia.

In a pilot study, 32 patients with Philadelphia chromosome-positive chronic myelogenous leukemia were treated with intensive chemotherapy induction followed by interferon-alpha (IFN-A) maintenance. Intensive chemotherapy consisted of three cycles of daunorubicin 120 mg/m2 on day 1, cytarabine 80 mg/m2 daily for 10 days, vincristine 2 mg on day 1, and prednisone 100 mg daily for 5 days (DOAP). Maintenance therapy with IFN-A at a doses of 3 x 10(6) to 5 x 10(6) units/m2 daily was adjusted according to counts and toxicity. The outcome of patients was compared with a matched historic population of 64 patients treated with IFN-A alone. Overall, 60% of patients had a cytogenetic response (partial or complete) with induction chemotherapy, but only eight (25%) had a sustained cytogenetic response with IFN-A maintenance. After a median follow-up of 67 months, the 6-year survival rate of the 32 patients was 58%, compared with 36% for the matched historic group (P = 0.084). The incidence of lymphoid blastic transformation in the two groups was 25% and 48%, respectively (P = 0.10) and durable cytogenetic responses, 25% and 19%, respectively (P = 0.48). In summary, the addition of intensive chemotherapy induction to IFN-A maintenance does not improve the survival rate, incidence of lymphoid blastic transformation, or incidence of durable cytogenetic response compared with the results achieved with IFN-A therapy alone.

Adolescent↗
PubMed1992

Methadone maintenance detoxification fear: a study of its components.

These studies added three hypothesized fear components to the Detoxification Fear Survey Schedule (DFSS-14) and compared its psychometric properties to the original. Two disparate methadone maintenance populations (N = 226) were used in scale development. Thirty-one items and three factors emerged. A validation sample (N = 159) from two diverse methadone maintenance populations yielded a 27-item scale that discriminated between interview-diagnosed detoxification fear and non-fear (91.8% and 85.4% correctly classified). Finally, in methadone maintenance patients from three disparate programs in which the prevalence of detoxification fear was known, the DFSS-27 and DFSS-14 were compared. The DFSS-27 showed substantially improved sensitivity. The DFSS-27 seems a useful screen for detoxification fear in methadone maintenance, may aid intervention planning, and may prove a useful interventions outcome measure.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism.

BACKGROUND: Currently the most frequently used secondary treatment for patients with venous thromboembolism are vitamin K antagonists targeted at an INR of 2.5 (range 2.0 - 3.0). However, based on the continuing risk of bleeding and uncertainty regarding the risk of recurrent venous thromboembolism, there is discussion on the proper duration of treatment with vitamin K antagonists for these patients. Recently, several studies were published in which the risk and benefits of different durations of oral anticoagulants were compared in patients with venous thromboembolism. OBJECTIVES: The objective of this review was to evaluate efficacy and safety of different durations of treatment with vitamin K antagonists in patients with symptomatic venous thromboembolism. SEARCH STRATEGY: The reviewers sought publications through computerized searches of MEDLINE and EMBASE, and by hand-searching relevant journals, using the search strategy described by the Cochrane Review Group on Peripheral Vascular Diseases. They also contacted colleagues. SELECTION CRITERIA: Randomized controlled clinical trials comparing different durations of treatment with vitamin K antagonists in patients with symptomatic venous thromboembolism. DATA COLLECTION AND ANALYSIS: Two reviewers extracted the data and assessed the quality of the trials independently. MAIN RESULTS: Four studies with a total of exactly 1500 patients were included. A consistent reduction for the risk of recurrent events was observed during prolonged treatment with vitamin K antagonists (OR 0.15; 95% CI [0.10 - 0.23]) independent of the period elapsed since the index thrombotic event. A 'rebound' phenomenon, i.e. an excess of recurrences shortly after cessation of the prolonged treatment was not observed (OR 1.11; 95% CI [0.71 - 1.75]). In addition, a substantial increase in bleeding complications was found during the entire period after randomization (OR 7.75; 95% CI [1.08 - 55.57]). REVIEWER'S CONCLUSIONS: In conclusion this meta-analysis shows that treatment with vitamin K antagonists reduces the risk of recurrent venous thromboembolism as long as it is used. However, the absolute risk of recurrent venous thromboembolism declines over time, while the risk for major bleeding remains. Thus, the efficiency of vitamin K antagonist administration decreases over time since the index event.

Anticoagulants↗
PubMed2006

Oral betamimetics for maintenance therapy after threatened preterm labour.

BACKGROUND: Some women who have threatened to give birth prematurely, subsequently settle. They may then take oral tocolytic maintenance therapy to prevent preterm birth and to prolong gestation. OBJECTIVES: To assess the effects of oral betamimetic maintenance therapy after threatened preterm labour for preventing preterm birth. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Trials Register (June 2005) and MEDLINE (from 1966 to August 2003). SELECTION CRITERIA: Randomised controlled trials comparing oral betamimetic with alternative tocolytic therapy, placebo or no therapy, for maintenance following treatment of threatened preterm labour. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the selection criteria and carried out data extraction and quality assessment of studies. MAIN RESULTS: Eleven randomised controlled trials (RCTs) were included. No differences were seen for admission to the neonatal intensive care unit when betamimetics were compared with placebo (relative risk (RR) 1.29, 95% confidence interval (CI) 0.64 to 2.60; one RCT of terbutaline with 140 women) or with magnesium (RR 0.80, 95% CI 0.43 to 1.46; one RCT of 137 women). The rate of preterm birth (less than 37 weeks) showed no significant difference in four RCTs, two comparing ritodrine with placebo/no treatment and two comparing terbutaline with placebo/no treatment (RR 1.08, 95% CI 0.88 to 1.32, 384 women). No differences between betamimetics and placebo, no treatment or other tocolytics were seen for perinatal mortality and morbidity outcomes. Some adverse effects such as tachycardia were more frequent in the betamimetics groups than the groups allocated to placebo, no treatment or another type of tocolytic. AUTHORS' CONCLUSIONS: Available evidence does not support the use of oral betamimetics for maintenance therapy after threatened preterm labour.

Administration, Oral↗
PubMed1999

A staged approach to the treatment of Wegener's granulomatosis: induction of remission with glucocorticoids and daily cyclophosphamide switching to methotrexate for remission maintenance.

OBJECTIVE: To determine the efficacy of a daily cyclophosphamide (CYC) and glucocorticoid induction and methotrexate (MTX) remission-maintenance regimen for the treatment of Wegener's granulomatosis (WG). METHODS: An open-label, prospective, standardized trial for the treatment of WG was performed using CYC and glucocorticoids for remission induction and MTX for remission maintenance. Thirty-one patients were enrolled in this study. Outcome was assessed using predetermined definitions based on clinical characteristics and pathologic, laboratory, and radiographic findings. RESULTS: The use of CYC and glucocorticoids for remission induction and MTX for remission maintenance resulted in disease remission for all 31 patients. The median time to remission was 3 months and the median time to discontinuation of glucocorticoids was 8 months. No patients have died, and 5 patients (16%) have had disease relapses at a median of 13 months after achieving remission. Only 2 patients (6%) have had to withdraw from the trial as a result of medication toxicity. CONCLUSION: The use of CYC and glucocorticoids for remission induction and MTX for remission maintenance was shown by this study to be an acceptable alternative therapy for patients with active WG, including those with severe disease at onset.

Adolescent↗
PubMed2005

Quantifying maintenance requirements from the steady-state operation of a two-phase partitioning bioscrubber.

An innovative method for directly and explicitly quantifying the maintenance energy requirements of pure cultures growing on volatile organic compound (VOC) substrates in a two-phase partitioning bioscrubber is described. Direct evidence of maintenance energy requirements of Achromobacter xylosoxidans Y234 is provided both through observed reductions in the macroscopic biomass-to-substrate yield with decreasing specific growth rates, but more remarkably through achievement of steady-state operation. The data conclusively show that maintenance activities do occur in the two-phase partitioning bioscrubber and clearly illustrate the importance of this phenomenon to the operation of this process, and similar bioreactor systems. While benzene was selected as the principal, sole substrate of interest in this study, ethylbenzene degradation experiments were also subsequently performed to illustrate and confirm the general applicability of the proposed technique, as well as the potential capabilities of the two-phase partitioning bioscrubber for the continuous treatment of waste gases containing various VOCs. The proposed method has been shown to generate maintenance energy estimates that are consistent with those obtained while employing more widely recognized estimation strategies, further validating its capabilities. The proposed steady-state mode also offers key operational advantages in terms of decreased disposal requirements in two-phase partitioning bioscrubbers. (c) 2005 Wiley Periodicals, Inc.

Achromobacter denitrificans↗
PubMed1978

Maintenance requirements for bacteria growing on C1-compounds.

The maintenance coefficient, ms (mmol substrate/g cell dry wt hr), of two distinct groups of C1-utilizing bacteria has been determined by growing the organisms in an aerobic continuous culture limited by different C1 growth substrates. For growth on methanol, ms = 2.5 +/- 0.3 for Pseudomonas C; 3.9 +/- 0.7 for Ps. methylotropha (these bacteria utilize methanol via the ribulose monophosphate pathway of formaldehyde fixation); 1.5 +/- 0.2 for Pseudomonas 1, and 2.3 +/- 0.4 for Pseudomonas 135 (the latter bacteria utilize C1-compounds via the serine pathway). For growth on formaldehyde, ms = 1.5 +/- 0.3 for Pseudomonas 1 and 2.7 +/- 0.7 for Pseudomonas 135, whereas on formate the values for ms are 1.0 +/- 0.2 and 4.4 +/- 1.3; respectively. Although the maintenance coefficients did not differ systematically between the two groups of bacteria, the maintenance requirements per generation of the serine pathway bacteria were considerably higher (8.7 vs. 3.9) owing to their slower growth rate. The maximum molar yield values, YMmax (g cell dry wt/mol substrate utilized), corrected for the maintenance energy of bacteria which utilize C1-compounds via the ribulose monophosphate pathway averaged 19.1 when grown on methanol, while the values for bacteria which use the serine pathway averaged 13.5. On formaldehyde an average value of 11.5 is obtained and on formate the average value was 7.4 in the serine pathway bacteria.

Adenosine Triphosphate↗
PubMed2007

Predictors of weight maintenance after hospital discharge in adolescent anorexia nervosa.

OBJECTIVE: To analyze variables that predict weight maintenance in adolescent anorexia nervosa. METHOD: The Eating Attitudes Test, the Beck Depression Inventory, the Leyton Obsessional Inventory, the State and Trait Anxiety Inventory, and the Anorexia Nervosa Stages of Change Questionnaire were administered to 49 anorexia nervosa patients (mean age 14.3 years, SD 1.7) consecutively admitted to an eating disorder unit. They were evaluated at admission, at discharge, and after nine months follow-up. RESULTS: At discharge, patients had improved in body mass index (p < .001), eating attitudes (p = .002), depressive symptomatology (p = .001), and motivation to change (p < .001). Patients with good weight maintenance at follow-up had higher body mass index (p = .017) at admission, lower abnormal eating attitudes (p = .035), depressive symptomatology (p = .026), and higher motivation to change (p = .004) at discharge. Logistic regression analysis showed a high motivation to change at discharge and a high body mass index at admission to be predictors of weight maintenance. CONCLUSION: High motivation to change, low abnormal eating attitudes, depressive symptomatology at discharge, and high body mass index at admission are associated with weight maintenance in adolescent anorexia nervosa.

Adolescent↗
PubMed2004

A prospective controlled study of interferon-based therapy of chronic hepatitis C in patients on methadone maintenance.

We examined the feasibility of hepatitis C treatment in patients on opioid maintenance. One hundred patients with chronic hepatitis C, 50 on methadone maintenance, and 50 with no intravenous drug use or opioid maintenance for at least 5 years were prospectively matched for sex, age, hepatitis C virus (HCV) genotype and HCV RNA. The primary end point was undetectable HCV RNA at 24 weeks posttreatment. Treatment with peginterferon alfa-2b (1.5 microg/kg per week) and ribavirin (1000-1200 mg /day) was initiated for 24 weeks (HCV genotype 2, 3) or 48 weeks (HCV genotype 1, 4). Within the first 8 weeks of therapy, discontinuation due to noncompliance or patient request was observed in 22% (11/50) in the methadone group versus 4% (2/50) in the control group (P =.02). After 8 weeks, there was no significant difference in discontinuation due to noncompliance or patient request (4/39 [10%] vs. 4/48 [8%]). There was no difference in discontinuation of therapy because of viral failure or adverse events (10/50 methadone vs. 6/50 control, P =.41). At the end of treatment, 50% (25/50) in the methadone group and 76% (38/50) in the control group had undetectable HCV RNA (P =.01). Sustained viral response was 42% (21/50) in the methadone group and 56% (28/50) in the control group (P =.16). No serious psychiatric event occurred in either group. In conclusion, peginterferon and ribavirin seem reasonably safe and sufficiently effective in patients on methadone maintenance. Patients discontinuing therapy due to noncompliance or request did so early, thereby limiting the cost of an unsuccessful approach to treatment.

Adult↗
PubMed1994

Physical activity and long-term maintenance of weight loss.

To examine the effect of exercise on the long-term maintenance of weight loss, two types of literature were reviewed--correlational studies of predictors of long-term weight loss, and randomized trials comparing diet, exercise, and the combination of diet plus exercise. Both literatures were striking in the consistency with which activity emerged as a determinant of long-term maintenance of weight loss. The benefits of exercise for long-term weight maintenance were observed with different types of populations, diets, and exercise interventions. Several possible explanations for these positive effects of diet plus exercise are presented, and suggestions made for future research on ways to maximize the benefit of this approach to weight control. Since adherence to exercise may ultimately prove to be the cornerstone for long-term weight maintenance, studying ways to improve exercise adherence is recommended.

Combined Modality Therapy↗
PubMed1995

Partial maintenance of extra cancellous bone mass by antiresorptive agents after discontinuation of human parathyroid hormone (1-38) in right hindlimb immobilized rats.

The current study employs the immobilization (IM) rat model to induce osteopenia, parathyroid hormone (PTH) as the anabolic agent to restore bone mass, and 17 beta-estradiol, calcitonin, or risedronate as the maintenance agents to answer the following questions: How much cancellous bone loss occurs when PTH is withdrawn? Which antiresorptive or antiactivation agent maintains bone best? Ideally, what tissue-level histomorphometric conditions maintain added bone? Six-month-old female rats were treated with 200 micrograms PTH/day subcutaneously at 30 days post-IM for 75 days. Then PTH treatment was stopped and switched to a vehicle (no treatment), 10 micrograms calcitonin/kg/day, 10 micrograms 17 beta-estradiol/kg/day, or 5 micrograms risedronate twice weekly for another 15 days (early response) or 60 days (late response). The rats had their right hindlimb throughout the study. The current report deals only with the maintenance phase involving 92 animals. Bone histomorphometry was performed on the secondary spongiosa of the right proximal tibia metaphysis (PTM). Cessation of PTH treatment followed by vehicle administration for 15 days resulted in partial loss of trabecular bone area and thickness from stimulated bone resorption and the fall of all formation indices. By contrast, all three antiresorptive agents maintained the cancellous bone mass during the same period. However, after prolonged withdrawal of PTH for 60 days, we found that 17 beta-estradiol and calcitonin maintained the cancellous bone slightly better than no treatment, while risedronate partially protected it from the mechanostat-induced bone loss. The risedronate treatment retained 71% of the PTH-added bone while calcitonin retained 48%, estrogen 42%, and no treatment 32%. The favorable histomorphometry profile for maintenance was the sustained reduction in bone resorption and turnover and normal age-related bone balance. We concluded that 1) cessation of PTH treatment will result in the loss of two-thirds of the added bone in 60 days; 2) currently, risedronate at the dose level employed as a maintenance agent is far superior to 17 beta-estradiol or calcitonin because of its long retention in bone; however, a longer observation period might result in less difference; and 3) the ideal tissue-level histomorphometry continues depressing bone resorption and turnover and maintains a normal age-related bone balance. Furthermore, we found the "lose, restore plus add, and maintain (LRAM)" concept was successful in maintaining most of the PTH-induced extra bone by risedronate for 60 days. It was far superior to 17 beta-estradiol or calcitonin. Possibly the last two agents would be effective in maintaining a normal amount of bone but not in preserving an excessive amount of bone. Nevertheless, the current study further emphasizes that clinicians should consider using the LRM treatment strategy when they plan to treat osteoporosis with bone anabolic agents.

Animals↗