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Intensive maintenance therapy improves survival in adult acute nonlymphocytic leukemia: an eight-year follow-up.

Although a large majority of adult patients with acute nonlymphocytic leukemia (ANLL) achieve complete remission with present day therapy, eventual relapse and death is the rule rather than the exception. In an effort to improve survival, an intensive maintenance therapy approach was evaluated in 86 patients with ANLL in remission (median age 47 years) entered on study from 1978 to 1982. One-third of patients in remission were randomized to chemotherapy alone, one-third to splenectomy in addition to chemotherapy, and one-third to immunotherapy in addition to chemotherapy. The chemotherapy, which was identical in the three arms of the study, consisted of cytosine arabinoside plus 6-thioguanine, each given at a dose of 100 mg/m2 every 12 hr for a variable number of days, to render the patient's marrow aplastic, and was repeated every three months for three or more years. Median remission duration for patients in all three study groups is 21 months, with 58% of patients remaining in remission at one year. Twenty-five per cent of complete remitters are in continuous complete remission five to nine years after beginning intensive maintenance therapy. The median duration of survival of remitters is 25 months. Neither splenectomy nor immunotherapy had additional impact on remission duration or survival. In comparison with the results of earlier studies at the same institution in patients with similar characteristics, using identical remission induction therapy but less intensive maintenance therapy (46 patients), there has been a significant improvement in remission duration (p less than 0.001) and a significant impact on survival (p = 0.03) attributable to the use of intensive maintenance therapy. Intensive maintenance therapy may cure some adult patients with ANLL.

Acute Disease↗

Multicenter evaluation of six methods for predicting warfarin maintenance-dose requirements from initial response.

Warfarin maintenance-dose requirements predicted by six mathematical methods based on initial response to therapy were compared with patients' actual dose requirements in a multicenter trial. Data were collected for patients who had received an initial regimen of warfarin sodium 10 mg orally every 24 hours for three days and for whom a prothrombin time (PT) had been determined 16-20 hours after the third dose. Patients' individual dose requirements and PT values were recorded during one to three follow-up visits after discharge from one of seven medical centers. Prothrombin ratios (patient PT divided by control PT) calculated on day 4 were used for maintenance-dose prediction by five methods; a sixth method was based on the cumulative warfarin dose-PT response curve up to a PT value of 20 seconds. For 54 men and 30 women who qualified for the study, 197 maintenance-dose-PT response measurements were recorded; 95 in the first four weeks of therapy, 76 during weeks 5-12, and 26 at 6-12 months after initial treatment. Prothrombin ratios were within the therapeutic range (PT 1.5-2.5 times the control value) in 154 observations, and the mean actual warfarin sodium maintenance dose associated with therapeutic response was 7.6 mg/day. For patients with therapeutic prothrombin ratios, dose predictions by the five methods using prothrombin ratios (PRs) correlated significantly with actual dose requirements. The formula that predicted doses numerically closest to the actual dose is as follows: Dose = 11.17 - 21.08 (log PR). Only 45 observations were obtained for the sixth prediction method, and the correlation between actual and predicted doses was not significant. Initial warfarin maintenance-dose requirements can be predicted effectively based on one PT determination after administration of three daily 10-mg doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Predicting warfarin maintenance dosage based on initial response.

The relationship between initial response to warfarin sodium, as measured by prothrombin time, and warfarin maintenance dose was studied. Hospital patients received 10 mg of warfarin sodium daily until the prothrombin ratio (patient's prothrombin time/control) was 1.5 to 2.5. Patients subsequently were maintained at that warfarin dosage which maintained prothrombin ratios within this range. Twenty-two patients completed the study. A correlation was found between maintenance dose and the logarithm of the prothrombin ratio on the third day after initiating warfarin therapy (p less than 0.01, r = -0.74). There was no relationship between maintenance dose and the number of days needed to reach therapeutic response. Patients with baseline prothrombin ratios of less than one took significantly longer to reach therapeutic response than did patients with baselines of greater than one (p less than 0.01y. A simple yet scientific approach to determining warfarin maintenance dosage would seem to be feasible. The correlation found between maintenance dose and prothrombin ratio in this study would have to be applied cautiously and only after further validation.

Adult↗

Review of peptic ulcer maintenance trials.

One highly promising adjunct to acute treatment of peptic ulcer disease is long-term maintenance therapy with H2-receptor antagonists. Ranitidine, an agent that has been shown to be as effective as cimetidine in the acute therapy of healing ulcers, has also been evaluated for long-term prevention of ulcer recurrence. In such studies, 12 months of maintenance therapy with 150 mg of ranitidine at bedtime could sustain 75 to 90 percent remission in patients with healed duodenal ulcers and as high as 93 percent remission in patients with healed gastric ulcers. The relapse rate during a second year of maintenance was even lower, and most ulcers that did recur during these studies could be healed with a second course of twice daily ranitidine therapy. Relapse rates during maintenance with ranitidine are equal or better than comparable reports with cimetidine, about 20 percent for both drugs, and both have been well tolerated with a minimum of serious adverse reactions. As is now widely known, ranitidine appears to have substantially fewer side effects, including absence of interference with the microsomal enzyme metabolism of other drugs. The more convenient dosage schedule of ranitidine may be important for patient compliance with initial therapy of peptic ulcer disease, and the greater duration of ranitidine antisecretory effects may enhance effectiveness of long-term maintenance therapy by providing more complete inhibition of nocturnal acid secretion.

Cimetidine↗

[Remission maintenance therapy of non-Hodgkin's lymphoma with CHOP protocol].

We have retrospectively studied the problems concerning duration of maintenance therapy and chemotherapy regimens for non-Hodgkin's lymphoma treated at Shikoku Cancer Center Hospital. Four out of 15 complete remission cases had been in complete remission more than 3 years. Maintenance chemotherapy consists of CHOP protocol administering every 4 weeks and the median maintenance duration was 14 months with a median cycle of 14. Thereafter, patients have been followed up without receiving any therapy. The prospective study on maintenance therapy should be designed considering conditions such as 1) sufficient drug doses for cytocidal effects, 2) shorter maintenance period as possible, and 3) minimal side effects and complications to be expected.

Antineoplastic Combined Chemotherapy Protocols↗

Comparison of chemotherapy with immunotherapy for maintenance of acute lymphoblastic leukemia in children and adults.

Two hundred and seventeen patients, 1-50 yr old, with acute lymphoblastic leukemia in complete remission were randomized to receive a 1-yr consolidation chemotherapy of either type P, comprising 7 different drugs, or type M, consisting of methotrexate interspersed with prednisone and vincristine. Thereafter, they were randomized a second time to receive a 4-yr maintenance of either chemotherapy or immunotherapy, comprised of allogeneic blasts and bacillus Calmette-Guérin (BCG). Consolidation P caused more toxicity than consolidation M. However, comparison between the consolidation therapies P and M showed no significant difference, neither for disease-free interval nor for duration of survival. Chemotherapy showed more lethal toxicity in adults than in children. Comparison between chemotherapy (C) and immunotherapy (I) as maintenance treatment showed a significant (p = 0.016) superiority of C for disease-free interval (DFI). The difference was even more pronounced (p = 0.009) in the group with less than 8 g/dl of hemoglobin (Hb) at diagnosis before therapy. On the other hand, for patients with more than 8 g/dl Hb at diagnosis, presumably those with T-ALL, no difference in DFI was seen. No difference has been seen so far between maintenance therapies I and C concerning the duration of survival. The patients who were receiving maintenance I when they relapsed and who were consequently retreated by chemotherapy, survived longer from relapse than those patients retreated for relapse while receiving maintenance C.

Adolescent↗

System maintenance, problems, and enhancements.

The procedures required for software and hardware maintenance of a pharmacy computer system, and methods of dealing with operational and administrative problems of such systems, are described. Maintenance of software and hardware purchased from a vendor is usually provided by the vendor under contract. Repair maintenance is required for programs that do not run, produce incorrect results, or run too slowly. Update and revision maintenance is required when user requirements exceed the limits and design of the original program. Typical problems encountered with computer systems include slow computer response time, performance of maintenance personnel, turnover in user personnel, legal liabilities and restrictions, reliability of hardware and software, downtime, security, and changing configuration of equipment. Successful management of predictable and unpredictable problems with computer systems is accomplished through systematic review of the potential problem area and prospective planning.

Computers↗

Automobile inspection and maintenance programs: their role in reducing air pollution.

The development of Inspection and Maintenance Programs to control automobile emissions are one component of a comprehensive strategy to reduce automobile related air pollutants such as CO, NOX, and HC. Since the efficiency at which most motored vehicles are designed to limit pollutant emissions deteriorate with prolonged driving, an Inspection and Maintenance system is needed to restore the ability of the automobile to achieve its designed emission standards. Several types of approaches toward developing Inspection and Maintenance Programs in the U.S. including city, county, and state levels of organization and their effectiveness have been described. However, information on the efficiency of these approaches in achieving reductions in pollutant levels remain to be documented, as well as the cost effectiveness of such programs, and their acceptance by the public. In light of the important role that Inspection and Maintenance Programs have been projected to have in the U.S. in reducing automobile related air pollution, it is recommended that interdisciplinary research projects evaluating the multiple dimensions of Inspection and Maintenance Programs be initiated.

Air Pollution↗

Case-control analysis of allogeneic bone marrow transplantation versus maintenance chemotherapy for relapsed ALL in children.

In a retrospective study, the results of maintenance chemotherapy and allogeneic bone marrow transplantation (BMT) for children who reached a second complete remission (CR2) of their acute lymphoblastic leukemia (ALL) were compared. Case-control analysis was performed comparing 25 allogeneic transplant patients (cases) with 97 patients treated with maintenance chemotherapy (controls), who were matched for site of relapse, duration of CR1 and leukemia-free interval from onset of CR2. Until the first relapse, the children were treated according to standard protocols. The majority of patients suffered from a bone marrow relapse, mostly occurring more than 24 months after the onset of CR1. Remission reinduction treatment was heterogeneous. Patients treated with allogeneic BMT received high-dose chemotherapy and total body irradiation prior to BMT. Maintenance chemotherapy in controls was given for approximately 2 years. Following BMT, relapse rate was lower but the treatment-related mortality was higher compared with maintenance chemotherapy, resulting in leukemia-free survival rates at 4 years of 44% and 24%, respectively (not significant, NS). Case-control analysis of leukemia-free survival showed a hazard ratio of 0.756 in favor of BMT compared with chemotherapy (NS). If bone marrow relapses and central nervous system relapses were analyzed separately, a tendency to better leukemia-free survival was present after BMT compared with maintenance chemotherapy for patients with a relapse in the central nervous system, but for an isolated bone marrow relapse, no differences in leukemia-free survival were seen between the two groups of patients.

Antineoplastic Agents↗

Hairy cell leukemia. An update on a cohort of 93 patients treated in a single institution. Effects of interferon in patients relapsing after splenectomy and in patients with or without maintenance treatment.

We retrospectively analysed the results of interferon alpha-2 (IFN) treatment in 93 patients with hairy-cell leukaemia, of which 31 had previously undergone splenectomy. Induction treatment (3 x 10(6) U three times weekly for 12 months) was completed in 84 cases (90%). Peripheral hematological response was observed in 76 patients. Two patients had persistent splenomegaly, and response was observed in both cases after splenectomy. Five additional patients were responsive after 18-24 months of induction treatment and 1 was unresponsive. Of 28 patients on maintenance treatment (1 x 10(6) U 3 x per week), no patient relapsed after a median follow-up of 30 months. The toxicity level was acceptable and IFN resistance was not observed. On the other hand, of 56 patients without maintenance treatment, 37 relapsed at a median of 19 months. Thirty of 32 evaluable patients remained responsive to a second course of IFN. Of 19 patients without relapse, 11 had undergone splenectomy compared to 0/37 patients who relapsed (p < 0.001). In conclusion, the study shows the following, (1) IFN, provides excellent palliation without major toxic side effects; (2) long term maintenance was well tolerated and prevented peripheral haematological relapse; (3) lack of maintenance treatment was associated with peripheral haematological relapse requiring a second treatment; and (4) certain previously splenectomized patients may not require maintenance treatment. These long term results must be compared with the effectiveness and toxicity of new drugs, such as pentostatin and 2-chloro-deoxy-adenosine.

Cohort Studies↗

Psychotherapy in the maintenance treatment of depression.

A review of epidemiologic and clinical data on depression suggests that psychotherapy is both an important alternative as well as a supplement to medication for the maintenance treatment of depression. Psychotherapy is an alternative for patients during periods when medication may not be suitable or feasible (e.g. pregnancy, nursing, before or during major surgery, or in the elderly). Psychotherapy also has a role in maintenance treatment in dealing with the social and interpersonal consequences or triggers of recurrent depression. Although the number of continuation or maintenance treatment trials that include psychotherapy is quite limited, the efficacy of maintenance treatment in the delay of recurrence and enhancement of social functioning is best established for interpersonal psychotherapy. There are also some results concerning cognitive and behavioural therapies for maintenance treatment of depression.

Antidepressive Agents↗

The effects of nonsteroidal antiinflammatory drugs on methotrexate (MTX) pharmacokinetics: impairment of renal clearance of MTX at weekly maintenance doses but not at 7.5 mg.

OBJECTIVE: To determine the pharmacokinetics of methotrexate (MTX) with and without nonsteroidal antiinflammatory drugs (NSAID) at a 7.5 mg dose and higher usual maintenance doses of the drug. To determine the difference in pharmacokinetic variables when salicylate and nonsalicylate NSAID are administered with MTX at these doses. METHODS: Thirty patients receiving MTX chronically underwent a study of MTX pharmacokinetics after 7.5 mg doses of MTX with their usual NSAID and after the NSAID were withheld for 5 half-lives. Sixteen additional patients underwent pharmacokinetics studies with and without NSAID while receiving their usual weekly maintenance dose of MTX of 16.6 (3.6) mg (Mean +/- SD). RESULTS: No significant differences in pharmacokinetic variables were observed with and without NSAID at the 7.5 mg weekly dose of MTX. When patients received usual maintenance doses of MTX the renal clearance of MTX NSAID was 91.7 (26.4) ml/min versus 115.3 (34.4) ml/min without NSAID (p = 0.004). Creatinine clearance in patients taking usual maintenance doses increased from 77.5 (13.9) ml/min with NSAID to 95.3 (26.3) ml/min without NSAID (p = 0.05). A reduction in renal clearance of MTX was observed with maintenance dose MTX in both the 4 patients taking salicylates (p = 0.016) and the 12 patients taking nonsalicylate NSAID (p = 0.024). CONCLUSION: NSAID produce significant decreases in renal clearance of MTX and creatinine when patients consume their usual weekly dose of the drug, but not when they take a 7.5 mg dose. This effect is likely to achieve clinical relevance across the dose ranges used to treat patients with rheumatoid arthritis.

Aged↗

Antimicrobial therapy for Helicobacter pylori infection versus long-term maintenance antisecretion treatment in the prevention of recurrent hemorrhage from peptic ulcer: prospective nonrandomized trial on 125 patients.

OBJECTIVE: Our objective was to assess the effectiveness of therapy for Helicobacter pylori (HP) on the prevention of recurrent bleeding in patients with recent upper gastrointestinal hemorrhage from peptic ulcers. METHODS: We performed a prospective follow-up study without randomization on 125 consecutive patients (83 males and 42 females) who had presented with their first major episode of upper gastrointestinal hemorrhage from peptic ulcer (22 gastric and 103 duodenal ulcers). All 125 patients were HP-positive. During the acute phase of bleeding, all patients were treated with standard supportive measures. After the acute bleeding phase, patients were allocated to two treatment groups: 1) antimicrobial therapy-84 patients received one of the following three regimens: 1) amoxicillin 500 mg t.i.d. for 10 days + omeprazole 20 mg b.i.d. for 30 days; 2) clarythromycin 500 mg t.i.d. for 12 days + omeprazole 20 mg b.i.d. for 30 days; or 3) amoxicillin 500 mg t.i.d. for 10 days + metronidazole 500 mg t.i.d. for 10 days + colloidal bismuth subcitrate 240 mg b.i.d. for 30 days. For long-term antisecretion maintenance treatment, 41 patients were allocated to either omeprazole 20 mg once a day or ranitidine 150 mg once a day, for 1 yr. RESULTS: During the follow-up period, peptic ulcers recurred in six patients in the antibiotic group (7.14%) and 13 patients in the maintenance group (31.7%) (p < 0.001). The fraction of patients without recurrent bleeding was greater in the antibiotic group than in the maintenance group. Two patients in the antibiotic group (2.3%) and five in the maintenance group (12.1%) had recurrent hemorrhages (p < 0.1). CONCLUSION: Cure of HP infection reduces the recurrence of peptic ulcer and of rebleeding from ulcer disease more effectively than does long-term maintenance therapy.

Amoxicillin↗

The extent of maintenance required by implant-retained mandibular overdentures: a 3-year report.

Astra Tech implants were used to support implant-retained mandibular overdentures for 25 edentulous patients (12 with magnet retention and 13 with stud retention). The patients were followed for 3 years, and a detailed record was kept of the extent of maintenance required after placement of the dentures. There were 64 episodes of maintenance related to the overdentures in the magnet retention group and 63 episodes of maintenance in the stud retention group. Episodic maintenance was greatest during the first year, with the magnet group having 30 episodes and the stud group 34. The number of visits required for maintenance related to both the maxillary and mandibular dentures was 117 for the magnet retention group and 86 for the stud retention group. There was no statistically significant difference in the amount of postplacement care between the two groups.

Adult↗

Nutritional status as a predictor of morbidity and mortality in maintenance dialysis patients.

Many epidemiologic studies indicate that protein-energy malnutrition is a strong predictor of morbidity and mortality in maintenance hemodialysis and chronic peritoneal dialysis patients. Those parameters of protein-energy malnutrition that have been most clearly associated with morbidity or mortality include serum albumin, dietary protein intake as indicated by the protein equivalent of total nitrogen appearance (PNA, also referred to as PCR), and the predialysis serum urea nitrogen. In large scale clinical surveys, low predialysis serum creatinine, cholesterol, potassium, phosphorus, calcium, and bicarbonate also correlate with increased mortality rates in maintenance hemodialysis patients. These correlations may reflect an association between dietary intake and mortality. The paucity of data correlating energy intake or body composition (e.g., total body protein or nitrogen, skeletal muscle mass, total body fat) with clinical outcome may reflect the difficulty of obtaining these data in large scale prospective or retrospective analyses. The correlation between protein-energy malnutrition and increased morbidity and mortality rates does not prove that a higher protein and/or energy intake or a more optimal body composition will improve the patient's outcome. Prospective, randomized studies will be necessary to examine this question. However, two retrospective analyses of the effect of intradialytic parenteral nutrition on mortality rates in maintenance hemodialysis patients are consistent with the thesis that increased nutrient intake will reduce mortality in maintenance hemodialysis patients. Methods for assessing protein-energy nutritional status are discussed. There are essentially no data indicating that the more complicated and expensive techniques for nutritional assessment have important advantages over the more simple methods for the clinical management of maintenance dialysis patients.

Creatinine↗

Maintenance electroconvulsive therapy for Parkinson's disease.

In two patients with severe Parkinson's disease (PD) whose response to levodopa had decreased, the parkinsonian motor symptoms responded to acute and maintenance unilateral electroconvulsive therapy (ECT). Case 1 relapsed while taking antiparkinsonian medication 2 and 3 months after two brief courses of ECT. After another relapse, he received maintenance ECT and stayed well for 13 months. Case 2 relapsed 4 months after a course of ECT. Acute and maintenance ECT induced improvement for 14 months. Further relapses were treated with brief courses of ECT followed by maintenance ECT. Three and 4 years after their first ECT, the parkinsonian motor symptoms in these two patients are still markedly improved. Neuropsychological assessments did not suggest ECT-induced long-term cognitive impairment. We conclude that maintenance ECT should be considered in PD patients who relapse after having responded to an initial course of ECT. There is an urgent need for controlled studies.

Adult↗

Histamine H2 receptor antagonist-refractory oesophagitis: the efficacy of long-term omeprazole maintenance treatment.

BACKGROUND: Erosive oesophagitis refractory to high dose histamine H2 receptor antagonists (definition: failure to heal fully after > or = 3 months' treatment with cimetidine 3.2 g or ranitidine 0.9 g) responds well to omeprazole 40 mg daily but frequently relapses when the patients are put back on maintenance H2 receptor antagonists at medium or even high dose (e.g. cimetidine 1.6 g and 3.2 g, respectively). AIM: To investigate the efficacy of maintenance omeprazole 20 mg daily in refractory erosive oesophagitis. PATIENTS & METHODS: In this open, sequential study, patients with H2 receptor antagonist-refractory oesophagitis were healed on omeprazole 40 mg daily and then put on maintenance H2 receptor antagonists (cimetidine 1.6 g or 3.2 g). Relapses were re-treated with omeprazole 40 mg; upon rehealing, patients were put on maintenance omeprazole 20 mg daily for up to 4.5 years. RESULTS: Healing on omeprazole occurred in 38 out of 39 patients (97%) at 12 weeks. Only six of the 38 patients (16%) relapsed (asymptomatic in half) during subsequent maintenance treatment, whereas all had relapsed earlier on high dose H2 receptor antagonists. CONCLUSION: Within the limits of interpretation of an open study, omeprazole 20 mg daily seems effective in maintaining prolonged remission in this group of patients with H2 receptor antagonist-refractory oesophagitis.

Adult↗

Continuous maintenance with low-dose lansoprazole versus Helicobacter pylori eradication in the prevention of duodenal ulcer recurrence.

BACKGROUND/AIMS: Reduction of gastric acid secretion by maintenance treatment with antisecretory agents and eradication of H. pylori by antibiotics constitute the most effective therapeutic options in preventing duodenal ulcer relapse. The aim of this study was to compare the effect of a 12-month low-dose lansoprazole maintenance treatment with H. pylori eradication on the rate of ulcer relapse in H. pylori-positive duodenal ulcer patients. METHODOLOGY: After a healing phase with lansoprazole 30 mg/die or lansoprazole 30-60 mg/die plus antibiotics (amoxycillin, tinidazole and colloidal bismuth subcitrate), 84 patients with healed duodenal ulcer entered the follow-up phase. Thirty-eight patients with persistent H. pylori infection received lansoprazole 15 mg at bedtime, whereas 46 in whom H. pylori was eradicated during the acute phase received no active therapy during the 12-month follow-up. The two groups were well balanced concerning all demographic characteristics. Clinical controls were performed every 3 months or sooner in the event of symptomatic relapse. RESULTS: In terms of per protocol analysis, the overall rate of ulcer relapse at 6 months was 5.5% (2/36) in the maintenance group and 0 (0/42) in the antibiotic group. The corresponding figures at 12 months were 20.5% (7/34) and 5.7% (2/35), respectively (p:ns, 95% CI for the difference -0.30+0.02). On intent to treat analysis, the rate of ulcer relapse at 6 months was 5.2% (2/38) in the first group and 0% (0/46) in the second group: at 12 months the corresponding figures were 19.4% (7/36) and 4.3% (2/46), respectively (p=0.06; CI 95%: +0.016+0.28). No significant side effects were observed during long-term maintenance with lansoprazole. CONCLUSIONS: Continuous maintenance with low-dose lansoprazole may constitute a valuable alternative to H. pylori eradication for the prevention of relapse and complications in duodenal ulcer patients not suitable for, or who have failed, H. pylori eradication.

2-Pyridinylmethylsulfinylbenzimidazoles↗