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PubMed2002

First vs multiple episode schizophrenia: two-year outcome of intermittent and maintenance medication strategies.

Results of studies on intermittent neuroleptic treatment strategies in first episode (FE) schizophrenia have not been published. Aims of the present study were to elucidate the comparative efficacy of prodrome-based neuroleptic intervention in first vs multiple episode (ME) schizophrenia. As to the methods, three randomly assigned open neuroleptic treatment strategies were compared over 2 years in 363 schizophrenic outpatients (115 FE, 248 ME; ICD-9, RDC): maintenance medication vs two intermittent medication strategies (prodrome-based intervention and crisis intervention). Concerning relapse prevention, the results demonstrate that ME patients seemed to profit most from maintenance medication compared to both intermittent treatments, whereas FE patients did equally well under maintenance medication and prodrome-based intervention treatment. Psychopathology, social adjustment, subjective well-being, and side-effects after two years did not differ significantly between the FE and ME patients irrespective of treatment strategy. Concerning treatment adherence, FE patients complied better with prodrome-based intervention than with maintenance medication. Cumulative neuroleptic dosage was lowest in FE patients under intermittent treatment. In conclusion, maintenance medication is the best strategy for relapse prevention in ME patients. In FE patients, prodrome-based intermittent intervention seems to be equivalent or even better with respect to compliance and dosage applied.

Adult↗
PubMed2004

Maintenance and manipulation of information in schizophrenia: further evidence for impairment in the central executive component of working memory.

Impairments in working memory (WM) have been proposed to underlie various cognitive and functional impairments in schizophrenia. However, the nature and extent of the dysfunction remain unclear. The present study attempted to examine the integrity of sub-components of working memory in schizophrenia within the framework of the multiple-component working memory model proposed by Baddeley. Two sets of visuospatial and verbal delayed-response tasks were developed which had comparable formats and difficulties across domains. In Experiment 1, demands on the central executive (CE) were manipulated by requiring subjects either (1) to simultaneously maintain and transform information (maintenance-and-manipulation condition) or (2) just to maintain this information (maintenance-only condition). In Experiment 2, the amount of information to be maintained over the delay was parametrically varied to evaluate demands on the temporary maintenance component of working memory. Patients (N=16) performed worse than controls (N=16) in both conditions of Experiment 1; however, simultaneous maintenance and manipulation was associated with a significantly greater performance reduction in the patients. In Experiment 2, both patients (N=15) and controls (N=15) declined in performance, at equivalent rates, with increasing memory load. Parallel findings were observed for the verbal and visuospatial tasks. These results suggest that while both maintenance and central executive aspects of working memory are impaired in schizophrenic patients, the central executive may be more severely affected.

Adult↗
PubMed2002

Telomeric proteins regulate episomal maintenance of Epstein-Barr virus origin of plasmid replication.

Episomal maintenance and DNA replication of EBV origin of plasmid replication (OriP) plasmid maintenance is mediated by the viral encoded origin binding protein, EBNA1, and unknown cellular factors. We found that telomeric repeat binding factor 2 (TRF2), TRF2-interacting protein hRap1, and the telomere-associated poly(ADP-ribose) polymerase (Tankyrase) bound to the dyad symmetry (DS) element of OriP in an EBNA1-dependent manner. TRF2 bound cooperatively with EBNA1 to the three nonamer sites (TTAGGGTTA), which resemble telomeric repeats. Mutagenesis of the nonamers reduced plasmid maintenance function and increased plasmid sensitivity to genotoxic stress. DS affinity-purified proteins possessed poly(ADP-ribose) polymerase (PARP) activity, and EBNA1 was subject to NAD-dependent posttranslational modification in vitro. OriP plasmid maintenance was sensitive to changes in cellular PARP/Tankyrase activity. These findings imply that telomere-associated proteins regulate OriP plasmid maintenance by PAR-dependent modifications.

Chromatography, Affinity↗
PubMed1995

Maintenance therapies for late-life recurrent major depression: research and review circa 1995.

Major depression in the elderly is often a relapsing, chronic illness with high risk for chronic invalidism, poor treatment compliance, and suicide. In most cases, maintenance treatment to prevent recurrence and to enhance the quality of life is thought to be indicated. We review recent data from our ongoing studies that support both the efficacy and the safety of pharmacotherapeutic and psychotherapeutic maintenance treatments. However, the challenges of conducting maintenance therapy research (particularly with a placebo control) with the elderly are many, involving such areas as recruitment, retention, compliance, choice of outcome measures, and informed consent. We discuss each of these challenges and our responses to them. Finally, we suggest that maintenance therapy trials should be extended in several directions: (a) long-term treatment of bipolar and delusional subtypes in the elderly, as well as depression associated with progressive neurodegenerative disorders such as Alzheimer's dementia; (b) assessment of the benefits and risks of long-term therapy with other than tricyclic and monoamine oxidase inhibitor antidepressant agents, such as selective serotonin reuptake inhibitors; and (c) development of models of long-term course, including the interaction of treatments with medical and psychosocial variables that can have a profound impact on illness onset and offset. These issues are illustrated with a discussion of a new protocol designed to test the acute and maintenance efficacy of antidepressant therapy for depressed patients with Alzheimer's disease.

Alzheimer Disease↗
PubMed2002

Maintenance therapy in schizophrenia: a critical comment.

The paper's aim was to evaluate a rationale for maintenance therapy in schizophrenia and to consider the feasibility of intermittent targeted therapy as an alternative treatment strategy. This was achieved by a selected review of the relevant English-language literature published since 1966 through a Medline search and cross-referencing. Current scientific evidence for continuous maintenance therapy in schizophrenia was found equivocal as the randomization in clinical trials lumped together heterogeneous groups of patients, thereby creating a wide gap between research and clinical practice. In addition, the majority of studies took a narrow view of the concept of relapse. For these reasons, targeted intermittent treatment was probably prematurely discarded altogether. The rationale for use and optimal duration of maintenance antipsychotic pharmacotherapy for schizophrenia has not been adequately validated. The construct validity of outcome indicators currently used in maintenance treatment studies in schizophrenia should be reconsidered. Intermittent targeted treatment may represent a viable option in some clinical situations and warrant further evaluation. With the widespread use of atypical antipsychotics, current long-term maintenance strategies may need a reappraisal.

Antipsychotic Agents↗
PubMed2001

An intelligent tele-healthcare environment offering person-centric and wellness-maintenance services.

Worldwide healthcare delivery trends are undergoing a subtle paradigm shift--patient centered services as opposed to provider centered services and wellness maintenance as opposed to illness management. In this paper we present a Tele-Healthcare project TIDE--Tele-Healthcare Information and Diagnostic Environment. TIDE manifests an 'intelligent' healthcare environment that aims to ensure lifelong coverage of person-specific health maintenance decision-support services--i.e., both wellness maintenance and illness management services--ubiquitously available via the Internet/WWW. Taking on an all-encompassing health maintenance role--spanning from wellness to illness issues--the functionality of TIDE involves the generation and delivery of (a) Personalized, Pro-active, Persistent, Perpetual, and Present wellness maintenance services, and (b) remote diagnostic services for managing noncritical illnesses. Technically, TIDE is an amalgamation of diverse computer technologies--Artificial Intelligence, Internet, Multimedia, Databases, and Medical Informatics--to implement a sophisticated healthcare delivery infostructure.

Artificial Intelligence↗
PubMed2003

Treatment-latency and previous episodes: relationships to pretreatment morbidity and response to maintenance treatment in bipolar I and II disorders.

OBJECTIVE: To clarify relationships of treatment delay and pretreatment episode count with pretreatment morbidity and responses to maintenance treatments in bipolar disorders. METHODS: In 450 DSM-IV bipolar I (n = 293) or II (n = 157) patients (280 women, 170 men), we evaluated correlations of latency from illness-onset to starting maintenance treatment and pretreatment episode counts with pretreatment morbidity and treatment response. We considered morbidity measures before and during treatment, and their differences. RESULTS: Latency averaged 7.8 years, with 9.0 episodes per patient, before various maintenance treatments started. Morbidity (percentage of time-ill, episodes per year, first wellness-interval, or proportion of subjects hospitalized or having no recurrences) during maintenance treatment averaging 4.2 years was unrelated to treatment latency or pretreatment episode count. However, pretreatment morbidity was greater with shorter latency, resulting in larger relative reduction of morbidity after earlier treatment. CONCLUSIONS: Greater treatment latency and pretreatment episode count were not followed by greater morbidity during treatment, although longer delay yielded smaller during-versus-before treatment reduction in morbidity. Predictions that longer treatment delay or more pretreatment episodes lead to poorer responses to various maintenance treatments in bipolar I or II disorder were not supported.

Adult↗
PubMed2003

Alternatives to lithium and divalproex in the maintenance treatment of bipolar disorder.

OBJECTIVES: The role of lithium carbonate in the maintenance treatment of bipolar disorder is well established. Unfortunately, many patients fail to respond adequately to this agent or are unable to tolerate its adverse effects. Divalproex has become a commonly used alternative to lithium, but it also is ineffective or poorly tolerated in many patients. This article attempts to review the available data on maintenance therapy in bipolar disorder with a variety of anticonvulsants and antipsychotics (both conventional and novel), with reference to relevant studies in acute mania and bipolar depression as well. METHODS: Evidence on maintenance therapy and relevant acute-phase data were collected using MEDLINE database searches. RESULTS: Data on maintenance therapy with agents other than lithium and divalproex are sparse, and often derived from open, uncontrolled studies. Implications and flaws of available data are discussed. CONCLUSIONS: Other than lithium, there are few robust double-blind data to support the use of a variety of agents in the maintenance phase. However, uncontrolled data suggest that a number of agents merit further study.

Acetates↗
PubMed2006

High-maintenance interaction: inefficient social coordination impairs self-regulation.

Tasks requiring interpersonal coordination permeate all spheres of life. Although social coordination is sometimes efficient and effortless (low maintenance), at other times it is inefficient and effortful (high maintenance). Across 5 studies, participants experienced either a high- or a low-maintenance interaction with a confederate before engaging in an individual-level task requiring self-regulation. Self-regulation was operationalized with measures of (a) preferences for a challenging task with high reward potential over an easy task with low reward potential (Study 1) and (b) task performance (anagram performance in Study 1, Graduate Record Exam performance in Studies 2 and 3, physical stamina in Study 4, and fine motor control in Study 5). Results uniformly supported the hypothesis that experiencing high-maintenance interaction impairs one's self-regulatory success on subsequent, unrelated tasks. These effects were not mediated through participants' conscious processes and emerged even with a nonconscious manipulation of high-maintenance interaction.

Adolescent↗
PubMed2000

Physical activity behavior change: issues in adoption and maintenance.

The many benefits of participation in regular moderate- or vigorous-intensity physical activity are well established, yet more than 60% of the population is sedentary or insufficiently active. Published studies have revealed that behavior modification and cognitive-behavior modification can be successfully used to assist patients, healthy adults, and youth in the adoption of physically active lifestyles. However, few studies with adults and youth have examined the maintenance of physical activity behavior beyond 6 months of adoption of this behavior. Maintenance of physical activity is critically important because ongoing participation in the behavior is necessary to sustain health benefits. Knowledge of effective intervention strategies for long-term maintenance of physical activity is at an early stage. The authors provide a summary of what is known about the maintenance of physical activity behavior in adults and youth and how physical activity behavior relates to other health behaviors such as smoking, as well as recommendations for research on physical activity behavior change and maintenance.

Adolescent↗
PubMed2000

Promoting the maintenance of health behavior change: recommendations for the next generation of research and practice.

This article highlights several broad themes that emerged from the series of papers presented at the National Heart, Lung, and Blood Institute conference, "Maintenance of Behavior Change in Cardiorespiratory Risk Reduction," with a view to generating recommendations for the next generation of research and practice. Major recommendations center around the need for (a) new models of population health behavior change and maintenance that integrate individual-level with broader environmental and macro-level policy influences; (b) a fuller model of the maintenance process, which views maintenance more as a journey than as a destination; and (c) more theory-based and interdisciplinary research on the maintenance process and on strategies for assisting special populations and addressing more than one behavioral risk at a time.

Behavior Therapy↗
PubMed2005

Cognitive control in closed head injury: context maintenance dysfunction or prepotent response inhibition deficit?

The authors contrasted 2 potential explanations for the cognitive control deficits observed in closed head injury (CHI): a prepotent response inhibition deficit or a deficit in context maintenance, defined as the guidance of appropriate responding by task-relevant information. Healthy and CHI participants performed the traditional card Stroop task and a single-trial Stroop task sensitive to context maintenance deficits. As predicted by a context maintenance deficit, moderate to severe CHI participants showed higher error rates in the single-trial Stroop task only, and only when task instructions had to be maintained over a long delay. Moreover, context maintenance impairment and generalized slowing were both related to reports of daily functioning in CHI participants. Thus, context maintenance could be a useful framework for characterizing cognitive control deficits in CHI.

Adult↗
PubMed1999

Induction with mitomycin C, doxorubicin, cisplatin and maintenance with weekly 5-fluorouracil, leucovorin for treatment of metastatic nasopharyngeal carcinoma: a phase II study.

The combination of cisplatin and 5-fluorouracil (5-FU) (PF) is the most popular regimen for treating metastatic nasopharyngeal carcinoma (NPC) but it is limited by severe stomatitis and chronic cisplatin-related toxicity. A novel approach including induction with mitomycin C, doxorubicin and cisplatin (MAP) and subsequent maintenance with weekly 5-FU and leucovorin (FL) were designed with an aim to reduce acute and chronic toxicity of PF. Thirty-two patients of NPC with measurable metastatic lesions in the liver or lung were entered into this phase II trial. Mitomycin C 8 mg m(-2), doxorubicin 40 mg m(-2) and cisplatin 60 mg m(-2) were given on day 1 every 3 weeks as initial induction. After either four courses or remission was achieved, patients received weekly dose of 5-FU 450 mg m(-2) and leucovorin 30 mg m(-2) for maintenance until disease progression. With 105 courses of MAP given, 5% were accompanied by grade 3 and 0% were accompanied by grade 4 stomatitis. The dose-limiting toxicity of MAP was myelosuppression. Forty per cent of courses had grade 3 and 13% of courses had grade 4 leukopenia. No grade 3 or 4 cisplatin-related toxicity was observed. The overall response rate was 94% (95% confidence interval (CI) 84.9-100%) with a complete response rate (CR) of 6% (95% CI: 0-15.2%) and a good partial response (PR) rate of 28% (95% CI 11.7-44.6%), which was optionally defined as observance of only equivocal lesion identifiable under imaging study. Twenty-seven cases entered weekly FL maintenance phase. The median duration of maintenance with weekly FL was 38 weeks (8-91 weeks). There was no grade 3 or 4 toxicity noted during weekly FL. The median progression-free survival and overall survival were 11.6+/-0.4 and 18.1+/-3.6 months respectively. Six patients with a median follow-up of 19.8 months (9.6-41.0 months) were still alive and five of them had disease under control with FL. Good responders (CR and good PR) had better survival than less satisfactory responders (PR and stable disease) (P = 0.05). From Cox's multivariate regression analysis, the only significant prognostic factor for survival was good response to MAP (P = 0.042). Liver metastasis was the only significant variable in the best subset regression model that predicted good response to MAP (CR and good PR) (P = 0.027). MAP was an effective combination for metastatic NPC with minimal stomatitis and cisplatin-related toxicity but had significant myelosuppression. Weekly FL was a maintenance therapy with minimal side-effects. The response rate and overall survival of MAP-FL were better than series previously reported even when a subset of patients with poor prognosis was selected. MAP-FL's role as neoadjuvant or adjuvant therapy is worthy of further study.

Adult↗
PubMed1999

The prevalence of weight loss maintenance among American adults.

BACKGROUND: Previous studies suggest that few individuals achieve long-term weight loss maintenance. Because most of these studies were based on clinical samples and focused on only one episode of weight loss, these results may not reflect the actual prevalence of weight loss maintenance in the general population. DESIGN: A random digit dial telephone survey was conducted to determine the point prevalence of weight loss maintenance in a nationally representative sample of adults in the United States. Weight loss maintainers were defined as individuals who, at the time of the survey, had maintained a weight loss of > or =10% from their maximum weight for at least 1 y. The prevalence of weight loss maintenance was first determined for the total group (n = 500), and then for the subgroup of individuals who were overweight (body mass index BMI > or =27 kg/m2 at their maximum (n = 228). RESULTS: Weight loss was quite common in this sample: 54% of the total sample and 62% of those who were ever overweight reported that they had lost > or =10% of their maximum weight at least once in their lifetime, with approximately one-half to two-thirds of these cases being intentional weight loss. Among those who had achieved an intentional weight loss of > or =10%, 47-49% had maintained this weight loss for at least 1 y at the time of the survey; 25-27% had maintained it for 5 y or more. Fourteen percent of all subjects surveyed and 21% of those with a history of obesity were currently 10% below their highest weight, had reduced intentionally, and had maintained this 10% weight loss for at least 1 y. CONCLUSIONS: A large proportion of the American population has lost > or =10% of their maximum weight and has maintained this weight loss for at least 1 y. These findings are in sharp contrast to the belief that few people succeed in long-term weight loss maintenance.

Adult↗
PubMed2000

A descriptive study of weight loss maintenance: 6 and 15 year follow-up of initially overweight adults.

OBJECTIVE: To describe factors associated with long-term maintenance of weight loss. DESIGN AND SUBJECTS: We identified initially overweight individuals (body mass index >27 kg/m2, n=911) from the nationwide Finnish Twin Cohort and studied those who lost at least 5% of their body weight between 1975 and 1981. Subjects who had maintained weight loss until 1990 (38 men, 17 women) were compared to both regainers (28 men, 26 women) and the other overweight subjects in the cohort. MEASUREMENTS: Self-report data on weight, height, health behaviours and perceived well-being; self-report and register-based data on health status and use of medication. RESULTS: Only 6% of all overweight individuals lost and maintained at least 5% weight loss. In men weight loss maintenance was associated with a low level of stress and health-promoting behaviours but also with medical problems. Failure to maintain weight loss seemed to be associated with stressful life and past high alcohol intake. In women weight loss maintenance was associated with low initial well-being and health-compromising behaviours that improved after weight loss. CONCLUSION: Long-term weight loss maintenance is rare. Predictors of weight loss maintenance are different between women and men. International Journal of Obesity (2000)24, 116-125

Adult↗
PubMed2004

High protein intake sustains weight maintenance after body weight loss in humans.

BACKGROUND: A relatively high percentage of energy intake as protein has been shown to increase satiety and decrease energy efficiency during overfeeding. AIM: To investigate whether addition of protein may improve weight maintenance by preventing or limiting weight regain after weight loss of 5-10% in moderately obese subjects. DESIGN OF THE STUDY: In a randomized parallel design, 148 male and female subjects (age 44.2 +/- 10.1 y; body mass index (BMI) 29.5 +/- 2.5 kg/m2; body fat 37.2 +/- 5.0%) followed a very low-energy diet (2.1 MJ/day) during 4 weeks. For subsequent 3 months weight-maintenance assessment, they were stratified according to age, BMI, body weight, restrained eating, and resting energy expenditure (REE), and randomized over two groups. Both groups visited the University with the same frequency, receiving the same counseling on demand by the dietitian. One group (n=73) received 48.2 g/day additional protein to their diet. Measurements at baseline, after weight loss, and after 3 months weight maintenance were body weight, body composition, metabolic measurements, appetite profile, eating attitude, and relevant blood parameters. RESULTS: Changes in body mass, waist circumference, REE, respiratory quotient (RQ), total energy expenditure (TEE), dietary restraint, fasting blood-glucose, insulin, triacylglycerol, leptin, beta-hydroxybutyrate, glycerol, and free fatty acids were significant during weight loss and did not differ between groups. During weight maintenance, the 'additional-protein group' showed in comparison to the nonadditional-protein group 18 vs 15 en% protein intake, a 50% lower body weight regain only consisting of fat-free mass, a 50% decreased energy efficiency, increased satiety while energy intake did not differ, and a lower increase in triacylglycerol and in leptin; REE, RQ, TEE, and increases in other blood parameters measured did not differ. CONCLUSION: A 20% higher protein intake, that is, 18% of energy vs 15% of energy during weight maintenance after weight loss, resulted in a 50% lower body weight regain, only consisting of fat-free mass, and related to increased satiety and decreased energy efficiency.

Adolescent↗
PubMed2003

Maintenance efficacy of divalproex in the prevention of bipolar depression.

Breakthrough depression is a common problem in the treatment of bipolar disorder. Only one, recently published, double-blind, placebo-controlled trial has examined the efficacy of divalproex in the prevention of depressive episodes in bipolar patients. This report describes, in further detail, the findings from that trial of the effect of divalproex on multiple dimensions of depressive morbidity in bipolar disorder. A randomized, double-blind, parallel-group, multicenter study was conducted over a 52-week maintenance period. Bipolar I patients, who may have been treated with open-label lithium or divalproex and who met recovery criteria within 3 months of onset of an index manic episode, were randomized to maintenance treatment with divalproex, lithium, or placebo in a 2 : 1 : 1 ratio. Adjunctive paroxetine or sertraline for breakthrough depression was allowed in maintenance phase. Outcome measures were the rate of early discontinuation for depression, time to depressive relapse, proportion of patients with depressive relapse, mean change in Depressive Syndrome Scale score, proportion of patients receiving antidepressants, and time in the study. Among patients taking an antidepressant, a higher percentage of patients on placebo than divalproex discontinued early for depression. Patients who were previously hospitalized for affective episodes or took divalproex in the open period relapsed later on divalproex than on lithium during the maintenance period. Divalproex-treated patients had less worsening of depressive symptoms than lithium-treated patients during maintenance. Indices of severity of prestudy illness course predicted worse outcome in all treatment groups. Divalproex improved several dimensions of depressive morbidity and reduced the probability of depressive relapse in bipolar disorder, particularly in patients who had responded to divalproex when manic, and among patients with a more severe course of illness.

Adolescent↗
PubMed2004

Methadone maintenance reduces heroin- and cocaine-induced relapse without affecting stress-induced relapse in a rodent model of poly-drug use.

Although it is well established that methadone can be an effective treatment for opiate addiction, it is not clear how methadone maintenance affects cocaine use and cravings in individuals who self-administer both opiates and cocaine. In our attempt to explore the effect of methadone maintenance on the effects of cocaine, we first assessed the locomotor stimulatory effects of cocaine in rats maintained on methadone (0, 10, 20, or 30 mg/kg/day, via osmotic minipumps). Chronic methadone elevated baseline locomotion in a dose-dependent manner and did not reduce the direct stimulatory effects of cocaine (5 mg/kg). We then investigated the effects of the highest methadone maintenance dose (30 mg/kg/day) on heroin and cocaine seeking in extinction, and when it was precipitated by exposure to heroin, cocaine, or foot-shock stress in rats trained to self-administer both drugs in the same experimental context (heroin 0.05 mg/kg/inf; cocaine 0.5 mg/kg/inf, eight 3-h sessions each). In tests of reinstatement, rats responded selectively on the appropriate drug-associated lever after priming injections of heroin (0.25 mg/kg) or cocaine (20 mg/kg). Methadone maintenance blocked both cocaine- and heroin-induced reinstatement, but not stress-induced reinstatement, which was not lever selective. These results suggest that although methadone maintenance may not reduce the direct stimulatory effects of cocaine, it has the potential to reduce both spontaneous and cocaine-primed cocaine-seeking behavior.

Analysis of Variance↗