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Maintenance bacillus Calmette-Guerin immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group Study.

PURPOSE: Bacillus Calmette-Guerin (BCG) immunotherapy has been widely accepted as the optimal treatment for carcinoma in situ and high grade superficial transitional cell carcinoma. However, controversy remains regarding the role of maintenance therapy, and its long-term effect on recurrence and progression. MATERIALS AND METHODS: All patients in the study had transitional cell carcinoma of the bladder with carcinoma in situ or an increased risk of recurrence. The criteria for increased risk were 2 or more episodes of tumor within the most recent year, or 3 or more tumors within 6 months. At least 1 week following biopsy of carcinoma in situ and resection of any stage Ta or T1 transitional cell tumors 660 patients were started on a 6-week induction course of intravesical and percutaneous Connaught BCG. Three months following initiation of BCG induction therapy 550 consenting patients were stratified by purified protein derivative skin test and the presence of carcinoma in situ, and then randomized by central computer to receive BCG maintenance therapy (maintenance arm) or no BCG maintenance therapy (no maintenance arm). Maintenance therapy consisted of intravesical and percutaneous BCG each week for 3 weeks given 3, 6, 12, 18, 24, 30 and 36 months from initiation of induction therapy. The 384 eligible patients who were disease-free at randomization constitute the primary intent to treat analytic group because they could be followed for disease recurrence. All patients were followed for adverse effects of treatment, recurrence, disease worsening and survival. RESULTS: No toxicities above grade 3 were noted in the 243 maintenance arm patients. The policy of withholding maintenance BCG from patients with increased side effects may have diminished the opportunity to observe severe toxicity. Estimated median recurrence-free survival was 35.7 months (95% confidence interval 25.1 to 56.8) in the no maintenance and 76.8 months (64.3 to 93.2) in the maintenance arm (log rank p<0.0001). Estimated median time for worsening-free survival, defined as no evidence of progression including pathological stage T2 disease or greater, or the use of cystectomy, systemic chemotherapy or radiation therapy, was 111.5 months in the no maintenance and not estimable in the maintenance arm (log rank p = 0.04). Overall 5-year survival was 78% in the no maintenance compared to 83% in the maintenance arm. CONCLUSIONS: Compared to standard induction therapy maintenance BCG immunotherapy was beneficial in patients with carcinoma in situ and select patients with Ta, T1 bladder cancer. Median recurrence-free survival time was twice as long in the 3-week maintenance arm compared to the no maintenance arm, and patients had significantly longer worsening-free survival.

Adjuvants, Immunologic↗

The effect of maintenance narrow-band ultraviolet B therapy on the duration of remission for psoriasis: a prospective randomized clinical trial.

BACKGROUND: Narrow-band (311 nm) UVB is an effective treatment modality for moderate to severe psoriasis. The effect of maintenance narrow-band UVB on the duration of remission is unknown. AIM: To determine whether maintenance narrow-band UVB affects the duration of remission. METHODS: After clinically significant improvement [defined as 75% reduction in the initial Psoriasis Area and Severity Index (PASI) = "PASI 75"], patients were randomly assigned to one of two groups, namely maintenance and no maintenance. The first group received 2 months of maintenance therapy; the second group received no further treatment. Both groups were followed up for 1 year. RESULTS: At the end of 12 weeks, 46 of 50 patients (92%) achieved "PASI 75". Of these 46 patients, 32 had plaque-type psoriasis and 14 had guttate-type psoriasis. The numbers of patients assigned to the maintenance and no maintenance groups were 22 and 24, respectively. At the end of the study, 12 of the 22 patients (55%) in the maintenance group and, by contrast, eight of the 24 patients (33%) in the no maintenance group were still in remission. When the patients in both groups were categorized according to the type of psoriasis, eight of 14 (57%) patients with plaque-type psoriasis in the maintenance group and, by contrast, three of 18 (17%) in the no maintenance group were still in remission. Although numerically significant, life-table analysis indicated no statistically significant difference for the probability of remaining in remission between maintenance and no maintenance groups. CONCLUSIONS: The results provide some evidence that maintenance narrow-band UVB may achieve longer remission durations for patients with plaque-type psoriasis.

Adolescent↗

Impact of the initial doses of rocuronium and pancuronium on subsequent maintenance for neuromuscular block.

PURPOSE: To determine the impact of the neuromuscular blocking agent given for intubation on the duration of effect of multiple maintenance doses of pancuronium and rocuronium. METHODS: Seventy-eight subjects were randomly assigned to receive one of four dosing combinations for intubation and neuromuscular maintenance: rocuronium for intubation and maintenance, rocuronium for intubation and pancuronium for maintenance, pancuronium for intubation and rocuronium for maintenance, or pancuronium for both. Each time that the first twitch response returned to 25% of the baseline value, the duration of the dose was determined and another maintenance dose was administered. The duration of action of the maintenance doses was compared between the groups. RESULTS: Twitch suppression from the first maintenance dose was shorter for subjects who received rocuronium for both doses (Group RR) compared with that for subjects that received pancuronium (Groups PR & PP) as their intubation dose (17.6 vs 34 & 59.8 min, respectively, P < 0.05). Subjects who received rocuronium followed by pancuronium (Group RP) showed a shorter duration of twitch suppression after the first maintenance dose than the group that received pancuronium for both doses (Group PP) (21.3 vs 59.8 min, P < 0.05). By the third maintenance dose, the influence of the intubating dose on the maintenance dose duration had essentially diminished. CONCLUSIONS: For combinations of rocuronium and pancuronium, the duration of twitch suppression after a maintenance dose is only dependent on the first agent given for the first two maintenance doses administered.

Adolescent↗

[Quality of life and tolerance of maintenance therapy in patients with multiple myeloma].

Questionnaires on the quality of life and tolerance of different parts of maintenance treatment were sent to a total of 83 patients with multiple myeloma. All patients were for more than one year on maintenance treatment which involved either interferon alpha monotherapy (I), 3 million u. three times per week till signs of relapse developed or sequence administration of interferon alpha and dexamethazone 40 mg on day 1 to 4, 10 to 13 and 20 to 23 and then after a four-week interval again interferon alpha, again till progression of the disease occurred. The patients evaluated the presence or absence of different undesirable effects of treatment during the first two weeks of treatment and throughout the year and listed their intensity into four categories defined in the questionnaire. The quality of life was evaluated by means of a basic module of the questionnaire of the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire version 3.0 (EORTC QLQ-C30). The results of the questionnaire are to a certain extent surprising as from the patients' answers ensues that this maintenance treatment is associated with more numerous undesirable effects than the physicians realized when in contact with the patient. In this summary we can list only the most frequent effects (deterioration of eyesight, impaired sleep, depressions, irritability and unrest, chill, pain in muscles and joints, general weakness and dyspnoea). From the questionnaires on the quality of life ensues a markedly poorer quality of life of these patients as compared with the healthy population. There are however no basic differences between individual groups. The questionnaires were handed only to patients who had maintenance treatment for more than one year and thus patients were eliminated where maintenance treatment was discontinued because of undesirable effects. To give a general idea of the tolerance of the above maintenance treatment the authors mention that to the date of Aug. 31, 2001 113 patients were randomized into one of the branches of maintenance treatment. Maintenance treatment had to be discontinued in 6% patients (in two instances on account of severe hypothyroidism, in one case on account of hallucinations, in three instances on account of severe mental depression caused by this treatment). Reduction of interferon doses in 20% patients usually because of cytopenia but also on account of psychic problem. To the question what length of prolongation of life compensates the undesirable effects of maintenance treatment the following replies were obtained from patients receiving ID, possibly I: 3 months--47.6 and 38.3%, 6 months--4.3 and 10.6%, 9 months--0 and 4.3%, 12 months--47.6 and 46.8% of the addressed patients. In reply to the question whether the patients would prefer, assuming equal effectiveness, a maintenance monotherapy with interferon alpha or dexamethazone more patients preferred interferon to dexamethasone. For practice ensues from this article informing on undesirable effects of maintenance treatment and the effect of maintenance treatment on the quality of life: 1. the necessity of thorough knowledge of physicians of all possible undesirable effects as only a doctor knowing possible undesirable effects of treatment can recognize them, 2. regular monitoring not only of the activity of the basic disease, but also undesirable effects of maintenance treatment and the influence of treatment on the patients' quality of life, 3. the necessity to assess the quality of life in clinical trials as an important parameter for deciding on the way of treatment.

Antineoplastic Agents↗

Computer-based vs manual health maintenance tracking. A controlled trial.

OBJECTIVE: To compare computer-based with manual health maintenance tracking systems to determine whether (1) a computer-based system will result in better provider compliance with the practice health maintenance protocol, (2) the incremental cost of operating a computer-based vs a manual health maintenance tracking system differs, and (3) inactive patients will respond to health maintenance reminders. DESIGN: Two-year prospective, randomized, controlled trial. SETTING: Rural, multiple-office, nonprofit, fee-for-service family practice. PATIENTS: Adult members of families in which at least one member had been seen by the practice within the past 2 years. INTERVENTION: A computer-based health maintenance tracking system that generated annual provider and patient reminders for all patients regardless of appointment status compared with a manual flowchart-based tracking system in which patient reminders were triggered by provider request. OUTCOME MEASURES: Provider compliance with the health maintenance protocol determined by preintervention and postintervention chart audits, costs of computer-based tracking, and response of inactive patients to health maintenance reminders. RESULTS: Overall provider compliance with the health maintenance protocol increased 15 percentage points in the computer-based tracking group and four percentage points in the manual group. The computer-based tracking group had significantly higher provider compliance than the manual group for eight of 11 procedures. The computer-based tracking system cost 78 cents per patient per year to operate. It was not associated with increased office visits or patient billings. CONCLUSIONS: Computer-based health maintenance tracking improved provider health maintenance compliance compared with a manual system. The finding that health maintenance compliance improved without a significant increase in patient visits or billings requires confirmation in other settings but suggests that considerable health maintenance can be incorporated into ongoing patient care.

Adult↗

Randomized prospective trial of ganciclovir maintenance therapy for cytomegalovirus retinitis.

We report the first randomized prospective comparative study of long-term maintenance ganciclovir (9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine, BW759U, DHPG) therapy for cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome (AIDS). Eleven retinitis patients who received a 10-day course of ganciclovir induction therapy and then were randomized to receive either immediate daily ganciclovir maintenance therapy or deferred maintenance (eight deferred maintenance, three immediate maintenance) were evaluated for drug efficacy. Median time to retinitis progression was 42 days for the immediate maintenance group compared with 16 days for the deferred maintenance group, (P = 0.07). After crossing over to maintenance therapy, patients in the deferred group had a median time to retinitis progression of 58 days compared to 16 days while not on maintenance therapy (P = 0.13). Only 9% of cultures obtained while patients received maintenance therapy were positive for cytomegalovirus, vs 40% of those obtained off maintenance (P less than 0.001). We can state then that maintenance therapy with ganciclovir delays, but does not halt, progression of cytomegalovirus retinitis and suppresses, but does not eradicate, cytomegalovirus shedding in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

Antibiotic versus maintenance therapy in the prevention of duodenal ulcer recurrence. Results of a multicentric double-blind randomized trial.

OBJECTIVES: Reduction of gastric acid secretion by maintenance therapy and eradication of Helicobacter pylori by antibiotic treatment have been shown to reduce duodenal ulcer relapse. This study compared the effect of two regimens, a 6-month maintenance on an H2 receptor antagonist versus a one-week antibiotic therapy, on the rate of duodenal ulcer relapse in duodenal ulcer patients with gastric H. pylori infection. METHODS: We conducted a 30-week, double-blind, double-dummy, multicentric clinical trial involving 119 patients (97 M, 22 F, mean age 39 +/- 14 years) randomly assigned to a daily dose of 40 mg famotidine for 6 weeks supplemented with, during the first week, either antibiotics (500 mg amoxicillin q.i.d. and 500 mg tinidazole t.i.d.-antibiotic group) or their placebo (maintenance group). Healed patients after 6 weeks entered the 6-month maintenance phase: the maintenance group received 20 mg famotidine at bedtime and the antibiotic group, a placebo. Endoscopy with antral biopsies was performed to allow a rapid urease test, culture and histological examination upon entry, after 6 weeks, 3 months, and 6 months and, whenever symptoms recurred. H. pylori status was regarded as positive if any one of these three tests was positive, and negative if all tests were negative. RESULTS: The 2 treatment groups were well balanced for all baseline characteristics. After 6 weeks, H. pylori was eradicated in 25 (45%) patients in the antibiotic group, and in 1 (2%) in the maintenance group (P < 0.01). In term of intention-to-treat, there was no significant difference in the healing rate after 6 weeks (93 and 83% in the antibiotic and maintenance groups, respectively; P = 0.15) or in the relapse rate after 6 months (13 and 28% in the antibiotic and maintenance groups, respectively; P = 0.17 Log-rank test). However, the overall failure rate (absence of healing, relapse) was lower (P = 0.04, Log-rank test) in the antibiotic group in which all relapses but one were observed in H. pylori positive patients. The rate of ulcer relapse (1/20) in patients of antibiotic group who remained free of H. pylori during the study, was significantly (P < 0.01) lower compared with that of H. pylori positive patients in the maintenance group (11/44). During the first 6-week period, more side effects were observed in the antibiotic group than in the maintenance group (4 vs 1 patient, respectively). CONCLUSIONS: Our results indicate no significant difference between ulcer relapse rates after 6 months following a one-week antibiotic therapy or long-term maintenance therapy. Short-term antibiotic therapy should be considered as a valuable alternative to the long-term maintenance therapy.

Adult↗

Prevention of recurrences of erosive reflux esophagitis: a cost-effectiveness analysis of maintenance proton pump inhibition.

PURPOSE: To determine the cost-effectiveness of three management strategies for healed erosive reflux esophagitis: maintenance therapy with a proton pump inhibitor (PPI) from the outset; no maintenance therapy unless a patient's symptoms recur once over a year; and no maintenance therapy unless a patient's symptoms recur twice over a year. MATERIALS AND METHODS: Decision analysis using data from randomized trials of lansoprazole, case series, and expert opinion. RESULTS: For patients with grade 4 esophagitis, maintenance from the outset is the most efficient approach. For all other patients, providing maintenance PPI after a patient experiences two recurrences is the least costly but least effective approach. The other two approaches prevent more recurrences: waiting to initiate maintenance therapy until symptoms recur once requires an additional $73 for each recurrence prevented whereas maintenance PPI from the outset requires an additional $819 for each recurrence prevented. Maintenance therapy from the outset is cost effective if symptoms of esophagitis cause a 22% or greater decrement in quality of life (using $50,000 per quality-adjusted life year gained as a cost-effectiveness definition). However, withholding maintenance until the time of a first recurrence is cost effective if symptoms cause a 2% or greater decrement in quality of life. CONCLUSION: For grades 2 and 3 esophagitis, providing maintenance therapy after a patient experiences a further recurrence is a preferred option that appears cost-effective across a wide array of assumptions. Maintenance therapy from the outset, however, appears cost-effective only for those patients who report a significant decline in quality of life associated with esophagitis or for those patients with baseline grade 4 esophagitis.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Feasibility and potential benefit of maintenance endoscopic variceal ligation in patients with unresectable hepatocellular carcinoma and acute esophageal variceal hemorrhage: a controlled trial.

BACKGROUND: Patients with unresectable hepatoma and acute esophageal variceal bleeding have extremely high rates of recurrent bleeding and mortality. This controlled study evaluates the feasibility and potential benefit of maintenance endoscopic variceal ligation in these patients. METHODS: Patients with unresectable hepatoma and acute esophageal variceal bleeding underwent emergent endoscopic variceal ligation. After hemostasis, patients were randomized to undergo maintenance or esophageal variceal ligation (EVL) as necessary (demand ligation). RESULTS: Fifty-four patients underwent maintenance EVL and 55 demanded EVL. One or more subsequent EVL session could be performed in only 30 patients (55.6%) in the maintenance group (actual maintenance ligation). Logistic regression analysis found that hepatic function determines the feasibility of maintenance ligation (Child-Pugh's A+B vs. C, OR 23.00: 95% CI [5.26, 100.66]). The survival and recurrent bleeding rates were similar in both groups. A subgroup analysis of patients with Child-Pugh's A and B hepatic reserve in both the maintenance EVL group (n = 24) and demand EVL group (n = 25) was performed to assess the potential benefit of maintenance ligation. Maintenance ligation reduced the rate of recurrent bleeding compared with demand ligation (p = 0.043). Cox regression showed that portal vein thrombosis and tumors in both hepatic lobes were also factors together with EVL that determined recurrence of bleeding. Survival was similar in both groups. CONCLUSIONS: Maintenance ligation is feasible in patients with unresectable hepatoma and variceal hemorrhage if they have a good hepatic reserve. Maintenance ligation might lower the rate of recurrent bleeding in this subgroup of patients.

Acute Disease↗

Interferon-alpha for induction and maintenance in multiple myeloma: results of two multicenter randomized trials and summary of other studies.

BACKGROUND: Interferon (IFN) treatment trials in multiple myeloma have yielded discordant results regarding response rates, maintenance duration, and survival times. Further randomized trials and global evaluations of available data are urgently needed for clarification. PATIENTS AND METHODS: 256 patients participated in a randomized trial, 125 on IFN + VMCP, and 131 on VMCP alone. 100 patients were randomized to IFN maintenance (n = 46) or were untreated controls (n = 54). Global evaluations are based on 1,518 patients in induction and 924 in maintenance trials. RESULTS: The induction trial demonstrated a significantly (p < 0.05) lower rate of progressive disease under IFN + VMCP (10.6%) than under VMCP (22.9%), but this benefit was limited to stage I or II patients. Median progression-free survival was longer in the IFN + VMCP arm (23.2 months vs. 15.8 months); median overall survival did not differ significantly (38.9 vs. 30.2 months). The IFN maintenance treatment trial showed significantly superior results in the IFN arm versus controls (median maintenance duration: 17.8 months and 8.2 months (p < 0.01), survival: 50.6 and 34.4 months (p < 0.05), respectively). Previous IFN treatment increased the benefits of IFN maintenance therapy. Adverse effects of IFN during induction were hematologic toxicity, fever, and infections, requiring dose reductions. Toxic effects of IFN maintenance treatment were mild. Global evaluations of randomized trials showed small but significant benefits of combined IFN induction therapy and significantly prolonged maintenance duration and survival under IFN maintenance. CONCLUSIONS: Presently available data support the use of IFN maintenance treatment because it significantly prolongs maintenance duration and survival. IFN added to induction chemotherapy resulted in minor improvements at the expense of increased toxicity, highlighting the need for better induction regimens.

Adult↗

Nine years of maintenance treatment with ranitidine for patients with duodenal ulcer disease.

Four hundred and sixty-four patients with duodenal ulcer disease received continuous maintenance treatment with ranitidine for up to 9 years. Treatment failure was defined as either the first symptomatic recurrence of ulcer or the first ulcer recurrence accompanied by haemorrhage. Life tables were constructed using the Kaplan-Meier product-limit method; comparisons of survival curves were performed using the log-rank test; and multivariate analysis was carried out using the Cox proportional hazards model. Results. The proportion of patients remaining free from symptomatic recurrence of ulcer during maintenance treatment with either 150 mg/day or 300 mg/day ranitidine was: 95% at 1 year; 88% at 3 years; 86% at 5 years; and 81% at 7 and 9 years (95% C.I. 76-86%). Young age and the absence of exposure to non-steroidal anti-inflammatory drugs (NSAIDs) at the time of diagnosis of ulcer were shown to increase the likelihood of developing ulcer recurrence. The rate of ulcer recurrence after 9 years of maintenance treatment (17%) was significantly less than that after 5 years without active anti-ulcer therapy (80%), P = 0.0001. The proportion of patients who remained free from ulcer haemorrhage during maintenance treatment was: 99.1% at 1 year and 98.1% at 5 and 9 years (95% C.I. 96.7-99.6%). The risk of haemorrhage was significantly greater in patients who were not receiving active treatment (12.4% at 5 years) than in patients receiving maintenance treatment (less than 2% at 9 years), P = 0.0001 (log-rank test). Patients who had originally presented with haemorrhage had an increased risk of further ulcer bleeding compared with patients who presented with pain (P = 0.0013). A significantly greater proportion of patients with NSAID-associated duodenal ulcers remained free from ulcer recurrence during maintenance treatment compared with patients suffering from 'idiopathic' ulcers (P = 0.0238), although there was no difference between the two groups in respect of haemorrhage during maintenance treatment. Conclusions. (a) Continuous maintenance treatment with ranitidine for up to nine years successfully prevents ulcer recurrence in more than 80% of patients with duodenal ulcer disease. (b) Young age increases the risk of ulcer recurrence during maintenance treatment with ranitidine. Ulcers associated with NSAID-intake at the time of diagnosis have a lesser risk of recurrence during maintenance treatment. (c) The risk of haemorrhage in patients with ulcer disease receiving maintenance treatment with ranitidine for nine years was less than 2% compared with greater than 12% in untreated patients observed for 5 years.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Health maintenance in a primary care clinic for urban, indigent adults.

OBJECTIVE: The objective was to examine the delivery of preventive health care services in an urban clinic for indigent adults and the impact of advanced practice nursing on these practices. DESIGN: The study design was a descriptive chart review. SETTING AND SUBJECTS: Data were collected in an urban outpatient clinic. Seven hundred sixty-five records were examined prospectively for health maintenance. Of these records, 523 were randomly selected and reviewed retrospectively for completion of health maintenance. The mean age of participants was 45.15 years (SD = 9.87); 92% were African American, and 48.9% were male. INSTRUMENTS: The Health Maintenance Form was used to record data about demographics, health history, care provider, and completion of 10 health maintenance items. METHODS: Records were reviewed prospectively prior to the patient's clinic visit. A form summarizing the patient's health maintenance status was placed at the front of the record. At least 4 weeks later, the record was reviewed a second time for completion of health maintenance items. This second review was the data collection phase. RESULTS: Completion of health maintenance items was found to be low. The most up-to-date areas were serum cholesterol (83.9%) and mammography (70.1%). The lowest levels were rectal examination (34.5%), pneumococcal vaccination (35%), and fecal occult blood test (37.1%). Patients followed up by a nurse practitioner had significantly more health maintenance areas up-to-date than did patients followed-up by the nurse practitioner-physician team, which in turn had significantly more areas up-to-date than did patients followed up by a physician alone. CONCLUSIONS: Health maintenance was accomplished at a low level, indicating that preventive health practices need to be re-evaluated. The nurse practitioner had the greatest impact on a patient's health maintenance being up-to-date.

Adult↗

Different relative importances of the par operons and the effect of conjugal transfer on the maintenance of intact promiscuous plasmid RK2.

The par region of the broad-host-range, IncP alpha plasmid RK2 has been implicated as a stability determinant by its ability to enhance the maintenance of mini-RK2 plasmids or heterologous replicons in a growing population of host cells. The region consists of two operons: parCBA, which encodes a multimer resolution system, and parDE, which specifies a postsegregational response mechanism that is toxic to plasmidless segregants. To assess the importance of this region to the stable maintenance of the complete RK2 plasmid in different hosts, we used the vector-mediated excision (VEX) deletion system to specifically remove the entire par region or each operon separately from an otherwise intact RK2 plasmid carrying a lacZ marker. The par region was found to be important to stable maintenance of RK2lac (pRK2526) in Escherichia coli and five other gram-negative hosts (Agrobacterium tumefaciens, Azotobacter vinelandii, Acinetobacter calcoaceticus, Caulobacter crescentus, and Pseudomonas aeruginosa). However, the relative importance of the parCBA and parDE operons varied from host to host. Deletion of parDE had no effect on the maintenance of pRK2526 in A. calcoaceticus, but it severely reduced pRK2526 maintenance in A. vinelandii and resulted in significant instability in the other hosts. Deletion of parCBA did not alter pRK2526 stability in E. coli, A. tumefaciens, or A. vinelandii but severely reduced plasmid maintenance in A. calcoaceticus and P. aeruginosa. In the latter two hosts and C. crescentus, the delta parCBA mutant caused a notable reduction in growth rate in the absence of selection for the plasmid, indicating that instability resulting from the absence of parCBA may trigger the postsegregational response mediated by parDE. We also examined the effect of the conjugal transfer system on RK2 maintenance in E. coli. Transfer-defective traJ and traG mutants of pRK2526 were stably maintained in rapidly growing broth cultures. On solid medium, which should be optimal for IncP-mediated conjugation, colonies from cells containing the pRK2526 tra mutants displayed significant numbers of white (Lac-) sectors on X-Gal (5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside) plates, whereas sectors appeared rarely in colonies from tra+ plasmid-containing cells. Both the traJ and traG mutations further reduced the maintenance of the already unstable deltapar derivative. Thus, these experiments with defined mutations in an intact RK2 plasmid have revealed (i) that the par region allows RK2 to adapt to the different requirements for stable maintenance in various hosts and (ii) that conjugal transfer can contribute to the maintenance of RK2 in a growing population, particularly under conditions that are favorable to RK2 transfer.

Bacterial Proteins↗

Ganciclovir. A pharmacoeconomic review of its use as intravenous or oral maintenance therapy in the management of cytomegalovirus retinitis in patients with AIDS.

Cytomegalovirus retinitis, an opportunistic infection caused by the herpesvirus cytomegalovirus, is a major cause of illness in patients with advanced AIDS. As infected patients require long term drug treatment to delay disease progression and minimise loss of vision, the disease is associated with substantial treatment costs which considerably increase overall expenditure on AIDS-related health care. During the last decade, intravenous ganciclovir has been a mainstay of treatment for patients with cytomegalovirus retinitis. However, notwithstanding its demonstrated efficacy as maintenance therapy for this condition, long term intravenous drug administration is both inconvenient and uncomfortable for many patients. Moreover, neutropenia and catheter-related infections have been reported commonly in patients receiving ganciclovir via the intravenous route. To overcome the limitations of intravenous ganciclovir, an oral formulation of the drug has been developed for use as maintenance therapy. In comparative clinical trials, both intravenous and oral ganciclovir maintenance therapy slowed disease progression and preserved visual acuity in patients with stabilised cytomegalo-virus retinitis, although there was evidence that the intravenous formulation was more effective in terms of delaying recurrence of active disease. This suggests that oral ganciclovir use should be limited to the treatment of patients without evidence of immediately sight-threatening cytomegalovirus retinitis. Three published cost analyses, which were based on efficacy and tolerability data derived from 2 randomised, comparative clinical trials, have shown that oral ganciclovir maintenance therapy offers cost advantages over intravenous maintenance therapy, despite the higher acquisition cost of the oral formulation. The higher overall costs of intravenous maintenance treatment, compared with oral therapy, were attributed to higher drug administration and adverse event treatment costs. In one analysis, estimated lifetime treatment costs of oral maintenance therapy were 25.2% lower than those of intravenous maintenance treatment. As yet, no formal cost-effectiveness evaluations of oral and intravenous ganciclovir have been published. Few published data are available regarding the relative effects of intravenous and oral ganciclovir on quality of life. However, in a health state utility analysis, there was a large overall preference among HIV-infected individuals for oral over intravenous maintenance treatment. In conclusion, oral ganciclovir appears to be a cost-saving and patient-preferred alternative to its intravenous counterpart for the maintenance therapy of AIDS patients with stabilised cytomegalovirus retinitis in whom there is no evidence of sight-threatening disease.

Acquired Immunodeficiency Syndrome↗

Comparison of feed energy costs of maintenance, lean deposition, and fat deposition in three lines of mice selected for heat loss.

Three replications of mouse selection populations for high heat loss (MH), low heat loss (ML), and a nonselected control (MC) were used to estimate the feed energy costs of maintenance and gain and to test whether selection had changed these costs. At 21 and 49 d of age, mice were weighed and subjected to dual x-ray densitometry measurement for prediction of body composition. At 21 d, mice were randomly assigned to an ad libitum, an 80% of ad libitum, or a 60% of ad libitum feeding group for 28-d collection of individual feed intake. Data were analyzed using 3 approaches. The first approach was an attempt to partition energy intake between costs for maintenance, fat deposition, and lean deposition for each replicate, sex, and line by multiple regression of feed intake on the sum of daily metabolic weight (kg(0.75)), fat gain, and lean gain. Approach II was a less restrictive attempt to partition energy intake between costs for maintenance and total gain for each replicate, sex, and line by multiple regression of feed intake on the sum of daily metabolic weight and total gain. Approach III used multiple regression on the entire data set with pooled regressions on fat and lean gains, and subclass regressions for maintenance. Contrasts were conducted to test the effect of selection (MH - ML) and asymmetry of selection [(MH + ML)/2 - MC] for the various energy costs. In approach I, there were no differences between lines for costs of maintenance, fat deposition, or protein deposition, but we question our ability to estimate these accurately. In approach II, selection changed both cost of maintenance (P = 0.03) and gain (P = 0.05); MH mice had greater per unit costs than ML mice for both. Asymmetry of the selection response was found in approach II for the cost of maintenance (P = 0.06). In approach III, the effect of selection (P < 0.01) contributed to differences in the maintenance cost, but asymmetry of selection (P > 0.17) was not evident. Sex effects were found for the cost of fat deposition (P = 0.02) in approach I and the cost of gain (P = 0.001) in approach II; females had a greater cost per unit than males. When costs per unit of fat and per unit of lean gain were assumed to be the same for both sexes (approach III), females had a somewhat greater estimate for maintenance cost (P = 0.10). We conclude that selection for heat loss has changed the costs for maintenance per unit size but probably not the costs for gain.

Adipose Tissue↗

Maintenance therapy of duodenal and gastric ulcer with H2-receptor antagonists.

Maintenance therapy with either ranitidine or cimetidine has been administered for up to 5 years to several hundred patients suffering from duodenal or gastric ulcer disease. Maintenance treatment prevented symptomatic ulcer relapse in approximately three-quarters of patients over this period of time. About half of symptomatic ulcer relapses occurred during the 1st year of maintenance therapy, and thereafter the symptomatic recurrence rate was extremely low. Potentially the most important effect of maintenance therapy was to reduce the incidence of ulcer complications, particularly haemorrhage (from 6.2% to 0.4% during the 1st year of duodenal ulcer maintenance). Maintenance therapy is therefore likely to reduce ulcer morbidity and to be cost-beneficial in patients who have previously experienced an ulcer complication and are at an increased risk of the same complication in the future. Maintenance therapy with 300 mg ranitidine daily was more effective than 150 mg ranitidine at night in smokers and may be a useful therapeutic option for smokers who relapse during maintenance therapy with 150 mg ranitidine at night or for smokers in whom it is mandatory to prevent ulcer recurrence because of a previous complication. Asymptomatic ulcers occurring during maintenance therapy are clinically benign, and rehealing such ulcers does not alter the subsequent clinical course. Point prevalences of asymptomatic reulceration should not be used when assessing the clinical value of maintenance therapy.

Anti-Inflammatory Agents, Non-Steroidal↗