Biochemical and genetic predictors and correlates of response to lamotrigine and folic acid in bipolar depression: Analysis of the CEQUEL clinical trial.

OBJECTIVES: CEQUEL (Comparative Evaluation of QUEtiapine plus Lamotrigine combination versus quetiapine monotherapy [and folic acid versus placebo] in bipolar depression) was a double-blind, randomized, placebo-controlled, parallel group, 2×2 factorial trial that examined the effect of adding lamotrigine and/or folic acid (FA) to quetiapine in bipolar depression. Lamotrigine improved depression, but its effectiveness was reduced by FA. We investigated the baseline predictors and correlates of clinical response, and the possible basis of the interaction. METHODS: The main outcome was change in depressive symptoms at 12 weeks, measured using the Quick Inventory for Depressive Symptoms-self report version 16 (QIDS-SR16). We examined the relationship between symptoms and lamotrigine levels, and biochemical measures of one-carbon metabolism and functional polymorphisms in catechol-O-methyltransferase (COMT), methylene tetrahydrofolate reductase (MTHFR) and folate hydrolase 1 (FOLH1). RESULTS: Lamotrigine levels were unaffected by FA and did not differ between those participants who achieved remission and those with persisting symptoms. When participants with subtherapeutic serum levels were excluded, there was a main effect of lamotrigine on the main outcome, although this remained limited to those randomized to FA placebo. None of the biochemical measures correlated with clinical outcome. The negative impact of FA on lamotrigine response was limited to COMT Met carriers. FOLH1 and MTHFR had no effect. CONCLUSIONS: Our results clarify that FA's inhibition of lamotrigine's efficacy is not a pharmacokinetic effect, and that low serum lamotrigine levels contributed to lamotrigine's lack of a main effect at 12 weeks. We were unable to explain the lamotrigine-FA interaction, but our finding that it is modulated by the COMT genotype provides a starting point for follow-on neurobiological investigations. More broadly, our results highlight the value of including biochemical and genetic indices in randomized clinical trials.

Clinical and regulatory implications of active run-in phases in long-term studies for bipolar disorder.

OBJECTIVE: The integration of new treatments into the market and routine clinical practice should be dependent on robustness of evidence from randomised controlled trials (RCTs). We assessed study designs of long-term studies for bipolar disorder of all second-generation antipsychotics (SGAs) submitted to the Food and Drug Administration (FDA) and the completeness of evidence submitted to the regulatory agency. METHOD: Systematic review of double-blind RCTs comparing SGAs with placebo or active drugs in adults. FDA website and electronic databases were searched until July 2013. RESULTS: Six placebo-controlled trials comparing aripiprazole, olanzapine, quetiapine and ziprasidone were found in the FDA website. Electronic searches found four additional RCTs about aripiprazole, olanzapine or quetiapine. All RCTs (either submitted to FDA or not) selected patients who responded to acute treatment to increase the treatment effect observed in the long-term phase (enrichment design). By contrast, in the prescribing information sheets for all SGAs, the reported indication was 'maintenance treatment of bipolar disorder'. CONCLUSION: Extrapolation of results from enrichment studies to the more general population of patients should be carried out cautiously because average treatment benefits are likely to be less in unselected patients. Clear guidance for regulatory submission of RCTs is needed.

Incentives and disincentives to participation by clinicians in randomised controlled trials.

BACKGROUND: Patients and clinicians need reliable, up-to-date information from randomised controlled trials (RCTs) on the costs and benefits of treatments. Recruitment difficulties arise when clinicians do not invite patients to participate in trials. OBJECTIVES: Primary: to assess the evidence for the effect of disincentives and incentives on the extent to which clinicians invite eligible patients to participate in RCTs of healthcare interventions. Secondary: to assess the evidence in relation to stated willingness to invite participation. SEARCH STRATEGY: 1. The Cochrane Methodology Register and Cochrane Database of Methodology Reviews were searched in May 2006 and Cochrane Central Register of Controlled Trials, National Research Register and ClinicalTrialsGov in April 2005.2. EMBASE, MEDLINE, CINAHL, PsycINFO and AMED were searched in April 2005.3. Reference lists of included studies were checked. SELECTION CRITERIA: Studies exploring the effect of (dis)incentives on clinicians' views and recruitment-related activity. DATA COLLECTION AND ANALYSIS: The information about included studies was insufficient for a full assessment of quality. Data on (dis)incentives were extracted and association with recruitment tested. MAIN RESULTS: No RCTs of interventions were identified. Eleven observational studies were included - two medical records reviews, one matched pair study, one clinician interview study, two studies documenting clinicians' decisions and five postal surveys. Three measures of recruitment were used, invitation to participate, entry into RCT and reported entry to RCT. Five studies explored the effect of patient characteristics. The effect of age and prognosis varied between trials. Six studies considered the association between clinicians' views and recruitment. Clinicians who agreed to participate because they were acquainted with the researchers were less likely to participate than those otherwise motivated (1 study, 2-sided p = 0.04 Fisher's exact test) and (Odds Ratio [OR] 0.4, 95% Confidence Interval [CI] 0.2 to 0.9, 1 study). Clinicians who had recruited were more likely to report some difficulties including "trials involve extra work" (OR 92.94, 95% CI 4.54 - 1902.11; p

Risperidone in long-term treatment for bipolar disorder.

BACKGROUND: Risperidone, an atypical antipsychotic, is used to treat acute manic episodes, particularly when psychotic symptoms are present. Drugs used to treat mania are often continued as long-term treatment to prevent relapse. There is a need for evidence of the effectiveness and safety of risperidone as long-term treatment. OBJECTIVES: To assess the randomised evidence for the efficacy and tolerability of risperidone compared with placebo or other active pharmacological treatments as long-term treatment for prevention or attenuation of further episodes of mood disorder in patients with bipolar disorder. SEARCH STRATEGY: The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR-Studies) was search on 12/10/2005, The Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, CINAHL and PsycINFO were searched in October 2005. Reference lists and English language textbooks were searched; researchers in the field were contacted. SELECTION CRITERIA: Randomised trials comparing risperidone with placebo or other drug in long-term treatment for prevention of depressive or manic relapses. DATA COLLECTION AND ANALYSIS: Not applicable. MAIN RESULTS: No randomised trials comparing risperidone with other treatments for the prevention of manic and depressive relapses were identified. AUTHORS' CONCLUSIONS: There is a need for randomised controlled trials comparing risperidone and other treatments for the prevention of relapse in bipolar disorder. The trials should involve randomisation of treatment for relapse prevention and involve long-term follow up.

Haloperidol alone or in combination for acute mania.

BACKGROUND: The main objectives in treating mania are to control dangerous behaviour, reduce suicide, produce appropriate acute sedation and shorten the episode of mood disturbance. Among different drugs, haloperidol has for many years been used in treating psychotic patients, but it has a troublesome side effect profile. OBJECTIVES: To assess the effects of haloperidol for the treatment of mania in comparison with placebo or other active drugs, either as monotherapy or add-on treatment. SEARCH STRATEGY: We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (11 October 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2005), MEDLINE (1966-2003), EMBASE (1980-2003), CINAHL (1982-2003), PsycINFO (1872-2003) and reference lists. We also contacted experts, triallists and pharmaceutical companies in the field. SELECTION CRITERIA: Randomised trials comparing haloperidol with placebo or other active treatment in the treatment of acute manic or mixed episodes in patients with bipolar disorder or schizoaffective disorder. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected adverse effects information from the trials. MAIN RESULTS: Fifteen trials involving 2022 people were included. Compared to placebo, haloperidol was more effective at reducing manic symptoms, both as monotherapy (Weighted Mean Difference (WMD) -5.85, 95% Confidence Interval (CI) -7.69 to -4.00) and as adjunctive treatment to lithium or valproate (WMD -5.20, 95% CI -9.26 to -1.14). There was a statistically significant difference, with haloperidol being less effective than aripiprazole (Relative Risk (RR) 1.45, 95% CI 1.22 to 1.73). No significant differences between haloperidol and risperidone, olanzapine, carbamazepine or valproate were found. Compared with placebo, a statistically significant difference in favour of haloperidol in failure to complete treatment (RR 0.74, 95% Cl 0.57 to 0.96) was reported. Haloperidol was associated with less weight gain than olanzapine (RR: 0.28, 95% CI 0.12 to 0.67), but with a higher incidence of tremor (RR: 3.01, 95% CI 1.55 to 5.84) and other movement disorders. AUTHORS' CONCLUSIONS: There is some evidence that haloperidol is an effective treatment for acute mania. From the limited data available, there was no difference in overall efficacy of treatment between haloperidol and olanzapine or risperidone. Some evidence suggests that haloperidol could be less effective than aripiprazole. Referring to tolerability, when considering the poor evidence comparing drugs, clinicians and patients should consider different side effect profiles as an important issue to inform their choice.

Risperidone alone or in combination for acute mania.

BACKGROUND: Risperidone, an atypical antipsychotic, is used to treat mania both alone and in combination with other medicines. OBJECTIVES: To review the efficacy and tolerability of risperidone as treatment for mania. SEARCH STRATEGY: The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR-Studies December 2004), The Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, CINAHL and PsycINFO were searched in December 2004. Reference lists and English language textbooks were searched; researchers in the field and Janssen-Cilag were contacted. SELECTION CRITERIA: Randomised controlled trials comparing risperidone with placebo or other drugs in acute manic or mixed episodes. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data from trial reports. Janssen-Cilag was asked to provide missing information. QUALITY ASSESSMENT: As in other trials of treatment for mania, the high proportion of imputed efficacy data resulting from rates of failure to complete treatment of between 12% and 62% may have biased the results. MAIN RESULTS: Six trials (1343 participants) of risperidone as monotherapy or as adjunctive treatment to lithium, or an anticonvulsant, were identified. Permitted doses were consistent with those recommended by the manufacturers of Haldol (haloperidol) and Risperdal (risperidone) for treatment of mania and trials involving haloperidol allowed antiparkinsonian treatment. Risperidone monotherapy was more effective than placebo in reducing manic symptoms, using the Young Mania Rating Scale (YMRS) (weighted mean difference (WMD) -5.75, 95% confidence interval (CI) -7.46 to -4.04, P<0.00001; 2 trials) and in leading to response, remission and sustained remission. Effect sizes for monotherapy and adjunctive treatment comparisons were similar. Low levels of baseline depression precluded reliable assessment of efficacy for treatment of depressive symptoms. Risperidone as monotherapy and as adjunctive treatment was more acceptable than placebo, with lower incidence of failure to complete treatment (RR 0.66, 95% CI 0.52 to 0.82, P = 0.0003; 5 trials). Overall risperidone caused more weight gain, extrapyramidal disorder, sedation and increase in prolactin level than placebo. There was no evidence of a difference in efficacy between risperidone and haloperidol either as monotherapy or as adjunctive treatment. The acceptability of risperidone and haloperidol in incidence of failure to complete treatment was comparable. Overall risperidone caused more weight gain than haloperidol but less extrapyramidal disorder and comparable sedation. AUTHORS' CONCLUSIONS: Risperidone, as monotherapy and adjunctive treatment, is effective in reducing manic symptoms. The main adverse effects are weight gain, extrapyramidal effects and sedation. Risperidone is comparable in efficacy to haloperidol. Higher quality trials are required to provide more reliable and precise estimates of its costs and benefits.

Olanzapine alone or in combination for acute mania.

BACKGROUND: Olanzapine, an atypical antipsychotic, is used in the treatment of mania both as monotherapy and combined with other medicines. OBJECTIVES: To review the efficacy and tolerability of olanzapine in the treatment of mania SEARCH STRATEGY: The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), The Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, CINAHL and PsycINFO were searched. SELECTION CRITERIA: Randomised trials comparing olanzapine with placebo or other drug in acute manic or mixed episodes. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data from trial reports MAIN RESULTS: Six trials (1422 participants) were included in the review. There was a high rate of failure to complete treatment on all treatments which may have biased the estimates of relative efficacy. Olanzapine was superior to placebo at reducing manic symptoms as monotherapy (Young Mania Rating Scale (YMRS) - weighted mean difference (WMD): -5.94, 95% CI -9.09 to -2.80) and in combination with lithium/valproate (YMRS) (WMD -4.01, 95% confidence interval -6.06 to -1.96). Olanzapine monotherapy was superior at reducing psychotic symptoms (PANSS positive symptoms subscale WMD: -3.54, 95% CI -5.28 to -1.80). Olanzapine was superior to divalproex at reducing manic symptoms (standardised mean difference (SMD): -0.29, 95% CI -0.50 to -0.08). Olanzapine did not lead to a statistically higher rate of clinical response than haloperidol (RR: 1.03, 95% CI 0.77 to 1.38). Fewer patients discontinued treatment on olanzapine than placebo (RR: 0.62, 95% CI 0.48 to 0.80). Olanzapine caused greater weight gain than placebo (WMD 1.91Kg, 95% CI 1.29 to 2.53) and somnolence (RR: 2.13 95% CI 1.62 to 2.79) but not more depressive symptoms (RR: 0.95, 95% CI 0.65 to 1.40) or movement disorder (WMD: -0.33, 95% CI -0.74 to 0.09). Olanzapine caused more prolactin elevation than placebo (RR: 4.35 95%CI 1.77 to 10.70). Olanzapine caused greater weight gain (WMD: 1.54, 95% CI 1.02 to 2.05); somnolence (RR: 1.80 95% CI 1.32 to 2.46) and movement disorders (SAS - WMD: 0.72 95% CI 0.11 to 1.33) than divalproex but less nausea ( RR: 0.36 95% CI 0.20 to 0.65). Olanzapine caused more weight gain than haloperidol (RR: 3.59, 95% CI 1.49 to 8.64) but less movement disorder (EPS RR: 0.10, 95% CI 0.04 to 0.24). REVIEWER'S CONCLUSIONS: Olanzapine is an effective treatment for mania and may be more efficacious than divalproex, though leads to more weight gain. Clinicians should consider both the relative efficacy and the different incidence of specific adverse effects of available drugs.

The effect of denture adhesive on mandibular movement during chewing.

BACKGROUND: The authors conducted a study to determine if reducing mandibular denture movement through the use of a denture adhesive improves chewing function in edentulous patients. METHODS: The authors compared the mean chewing rates of 10 denture wearers who used and did not use a denture adhesive with that of a control group of 10 dentate people. The authors recorded mandibular movements using a multichannel magnetometer tracking system while the subjects chewed standardized pieces of dried apricots and fresh white bread. They made recordings for the test subjects without the use of denture adhesive and at zero, two and four hours after Fixodent denture adhesive cream (Procter & Gamble Co.) was applied to the mandibular denture. RESULTS: The mean chewing rate for the control group was significantly faster than that of the test group at baseline (P < .01). The authors found statistically significant increases in the mean chewing rates for the test group after the denture adhesive was applied at all time points for both foods. None of the after--adhesive-application rates were significantly different from the control group's rate (P > .05). CONCLUSIONS: Use of denture adhesive increased the mean chewing rate in test subjects immediately after and at two and four hours after denture adhesive was applied to a rate that approximated that observed in control subjects (P > .05). CLINICAL IMPLICATIONS: These findings show that using a denture adhesive promotes a faster and more natural rate of chewing.

The rise of Clostridium difficile: the effect of length of stay, patient age and antibiotic use.

Hospitals in the UK have recently seen a marked increase in C. difficile for reasons which are unclear. Reduced standards of hygiene, increasingly elderly patients, greater cephalosporin use and longer hospital stay have been suggested. We retrospectively studied all cases of C. difficile diarrhoea at Princess Margaret Hospital, Swindon, over two years. Cephalosporins, patient age and LOS appeared unrelated to the rise in C. difficile; penicillins and macrolides were related. Our policy of using amoxycillin and clarithromycin for community-acquired pneumonia coincided with this study and may explain the observed rise in C. difficile.

Effect of health education on patients' beliefs about glaucoma and compliance.

A pretest-posttest control group experimental design (n = 100) was used to determine the effectiveness of an interactive patient education program compared with a didactic approach for persons with primary open angle glaucoma at a major specialist eye hospital in England. This study used a questionnaire with a knowledge test to explore patients' glaucoma knowledge, a series of vignettes to explore understanding of compliance and health motivation, and health locus of control scales to assess the effect of these variables. The improved posttest results (P = .000) suggest that patients benefit from education programs and that the ophthalmic nurse is an effective patient teacher. The interactive program has no statistically significant difference from the didactic presentation. Other types of interactive programs may prove to be more beneficial.

Effect of denture adhesive on retention of the mandibular and maxillary dentures during function.

The purpose of this study was to determine the effect of denture adhesive on retention of mandibular and maxillary dentures over a four-hour period. Denture movements were measured using an alternating magnetic field tracking device that determines the position of magnetic receiver coils relative to a transmitter coil positioned over the head. Ten adults with complete maxillary dentures and complete mandibular implant overdentures were enrolled in the study. Specially fabricated mandibular dentures contained a relief area that exposed the implant post which no longer anchored the denture, but now served as an attachment point for a receiver coil that measured mandibular movement. The denture coil was attached lateral to the post coil on a shelf cut into the denture. Mandibular denture movements were recorded as the difference between the mandible movement signal and the mandible + mandibular denture signals. Measurements of denture movements were made at baseline (no adhesive) and at 0, 2, 4 hours post-adhesive application with Fixodent cream for standardized chewing and biting. The MoveTrack signals were recorded on a digital data cassette recorder for subsequent computer analysis. The results of the measurements were analyzed using paired sample t-tests. Specifically, the following comparisons of movement means were made: mandibular vs. maxillary, baseline vs. post-baseline and successive changes (e.g., baseline vs. hour 0, hour 0 vs. hour 2, etc.). Results of these analyses showed that: 1) mandibular denture movements under both adhesive and non-adhesive conditions were significantly greater than maxillary denture movements; 2) the adhesive significantly reduced movement of the maxillary and mandibular dentures during both chewing and biting; and 3) the improvement occurred immediately post-application of the adhesive and was maintained for the four hours of follow-up.

Implementing a nurse-led telephone advice system in ophthalmology.

This article describes the background research I undertook to determine the potential for a telephone advice line in this major specialist eye hospital in the United Kingdom. The information gained was used to implement a computer-based telephone assessment system with guidelines. This system enables a registered nurse with an ophthalmic qualification to offer telephone triage and general information and advice about eye problems. The help line was identified as a service that would enhance the care of patients with eye problems, their carers, and health providers. The help line, "Moorfields Direct," was given a dedicated telephone number and was officially launched in February 1999.

(ECTO) nucleotidase kinetics observed by 31P-NMR spectroscopy: resolution of signals.

We used 31P-NMR to study the action of the drug ouabain, a digitalis glycoside, on the ecto-nucleotidase catalysed reaction pathway: [formula: see text] Even under conditions where it was impossible to resolve all resonances from the individual species, the rate constants for the individual steps may be evaluated by a chi 2 fit of equations describing the global kinetics to the NMR data. The fitted values of the reaction rate constants show no inhibition of any step in the reaction pathway, confirming previous results. This improved kinetic method can be used to evaluate the effect of different substrates, ions and drugs, both in intact or pathologically altered organs and in tissue subcellular fractions.

The effect of a computer-generated patient-held medical record summary and/or a written personal health record on patients' attitudes, knowledge and behaviour concerning health promotion.

OBJECTIVE: The aim of the study was to examine the effect of a computer-generated patient-held medical record summary (CHR) and/or a written personal health record (PHR) on patients' attitudes, knowledge and behaviour concerning health promotion. METHOD: It was conducted in five general practices in Oxfordshire. Patients aged 25-65 years in each practice were randomly assigned to receive either a CHR plus PHR, CHR only, PHR only, or no personal record. Patients were recruited by mail (one practice) or opportunistically by nurses (four practices). Health checks were carried out using the randomly assigned record, which the patient retained. Attitudes to patient-held records, and pre- and post-intervention knowledge and behaviour concerning health promotion, were assessed using questionnaires. Only those who responded to 'before' and 'after' questionnaires were included in the analysis. RESULTS: A sample of 261 patients was obtained from mail recruitment and 103 from opportunistic nurse recruitment. Patients receiving a CHR as part of mail recruitment were significantly more likely to attend for a health check (P = 0.016). Those receiving both PHR and CHR were more likely to keep (P = 0.014) and use (P = 0.029) the record. Those receiving PHR as part of the package improved their knowledge of health promotion and became more aware of and more likely to change their life-style (P = 0.022). CONCLUSIONS: The effectiveness of a computer-generated patient-held health summary and an explanatory booklet together is greater than either separately in changing patients' knowledge attitudes and behaviour concerning health promotion.

Retention and stability of the maxillary denture during function.

The objectives of this study were to provide a quantitative account of the extent to which the maxillary complete denture moves during function (chewing, swallowing, and speech production) and to determine whether differences in movement occur as a function of denture fit. A total of 24 patients were studied, 12 with poorly fitting dentures and 12 with well-fitting dentures. Denture movements were measured with a Myotronics kinesiograph that tracked the movements of a small magnet attached to the inferior surface of the denture. Results indicated that denture movement was greatest for the two chewing activities; varied extensively from individual to individual; and that there were no statistically significant overall movement effects as a function of fit. It was concluded that all maxillary dentures are subject to movements in all directions, but that the degree of movement is related more to the individual denture wearer than it is to the fit of the denture.

Activation and coordination patterns of the suprahyoid muscles during swallowing.

This study was undertaken to determine the activation and coordination patterns of the three suprahyoid muscles--geniohyoid, mylohyoid, and anterior belly of the digastric muscle--in elevating the larynx during swallowing. Electromyographic activity was also recorded from two intrinsic laryngeal muscles (vocalis and lateral cricoarytenoid) and the anterior genioglossus. Ten adults served as participants. Each participant produced 15 swallows of 15 mL of tap water both normally and with a 12-mm bite block placed between the molars. The electromyographic data were ensemble-averaged with a laboratory computer. Analyses showed that the three suprahyoid muscles were used selectively by different participants. Some participants used all three muscles for hyoid elevation, while others used different pairs of two of the muscles. The activation patterns of the suprahyoid muscles during swallowing also varied with respect to each other and the onset of the laryngeal constrictor muscles; however, use of at least one suprahyoid muscle always preceded the onset of the laryngeal adductors, indicating that larynx elevation consistently preceded glottal adduction. The way in which the muscles responded to the bite block varied considerably both within and among participants. Some maintained temporal stability but increased overall muscle activity; others reorganized temporal relations either with or without corresponding muscle activity adjustments. These findings suggest that the laryngeal elevation system is an adaptive function rather than an immutable action.

Effect of denture adhesive on the retention and stability of maxillary dentures.

This study used quantitative methods to measure the effects of a denture adhesive on the retention and stability of the maxillary denture. Denture movements were measured on 20 patients during standardized chewing, swallowing, and speaking activities, first with no adhesive, and then at 0, 2, 4, 6, and 8 hours after application of an over-the-counter cream adhesive. The major findings were that the denture adhesive produced a statistically significant improvement in the retention and stability of the maxillary denture during the various chewing, swallowing, and speaking activities, for up to 8 hours; there were no statistically significant differences in improvement between a poorly fitting and well-fitting denture; and patients were able to produce significantly greater levels of incisal bite force with the use of the adhesive.

Characteristics of muscle fatigue in patients with myofascial pain-dysfunction syndrome.

The purpose of this study was to compare the properties of muscle fatigue in the masseter and temporalis muscles of normal individuals and those with myofascial pain-dysfunction syndrome (MPD). The MPD muscle is presumed to have different characteristics of fatigue than its healthy counterpart; these characteristics can be quantitated using standard electromyogram (EMG) signal-processing techniques. A total of 18 patients diagnosed as having MPD comprised the experimental group and 15 adults with no history or present symptoms of temporomandibular joint pain and dysfunction served as controls. Surface EMG recordings were made for both the masseter and anterior temporalis muscles while the subject held an incisal bite force level of 10 N for as long as possible. The EMG data were transferred to a microcomputer where the power-density spectrum of the signals were calculated for 2-s samples at 10-s intervals. The mean power frequency (MPF) and power (root mean square, r.m.s.) of the signals were calculated from the power-density spectra. Results showed: (1) the endurance times were significantly shorter for the MPD patients; (2) the masseter was not active in three of 17 MPD patients; (3) decreases in MPF over time were significantly greater for the MPD patients than normal subjects; (4) increases in r.m.s. power were significantly greater over time for the MPD patients; (5) bandwidths of the power-density spectra were similar for the two groups. The implication of these results is the MPD muscle is not in a state of constant fatigue, as is currently believed, but rather demonstrates accelerated fatigue.