A randomized controlled crossover trial of aspirin for fatigue in multiple sclerosis

Pharmacotherapeutic options for multiple sclerosis (MS)-related fatigue are limited. Thirty patients were randomly assigned to aspirin (ASA) 1,300 mg/day or placebo in a double-blind crossover study. Results favored ASA for the main clinical outcomes: Modified Fatigue Impact Scale scores (p = 0.043) and treatment preference (p = 0.012). There were no significant adverse effects. The results warrant further study and support a role for ASA-influenced mechanisms, perhaps immunologic, in the generation of MS-related chronic fatigue.     

Therapeutic electrical stimulation in cerebral palsy: a randomized, controlled, crossover trial

The aim of this study was to evaluate the effect of therapeutic electrical stimulation (TES) applied to antagonists of spastic leg muscles on gross motor function in children with spastic diplegic cerebral palsy. Twelve children between 5 and 12 years of age completed a 24-month crossover study in which six were randomly assigned to receive TES for the first 12 months and the remaining six for the last 12 months. Physiotherapy and a home training program were not altered. All were evaluated blindly in terms of tests of motor function and video recordings at the start and at 12 and 24 months. At the end of the study parents/carers gave a subjective assessment of the effect of TES. No significant effect of TES on motor or ambulatory function was found on the blinded evaluation, but parents of 11 of the 12 children stated that TES had a significant effect. We conclude that it is unlikely that TES has a significant effect on motor and ambulatory function in spastic diplegia.     

Lamotrigine in treatment-resistant schizophrenia: a randomized placebo-controlled crossover trial.

BACKGROUND: There is no evidence from randomized, controlled trials that demonstrate effectiveness for any pharmacological treatment in clozapine-resistant schizophrenia. Since the introduction of chlorpromazine, all antipsychotics with proven efficacy on positive symptoms have been dopamine antagonists, but recent experimental data suggest that ketamine-induced positive schizophreniform symptoms in healthy subjects can be controlled by a glutamate antagonist lamotrigine. The hypothesis tested was that lamotrigine is more effective than placebo in the treatment of positive schizophrenic symptoms when combined with clozapine. METHODS: Thirty-four hospitalized treatment-resistant patients having chronic schizophrenia participated in a double-blind, placebo-controlled, 14-week, crossover trial where 200 mg/day lamotrigine was gradually added to their ongoing clozapine treatment. Clinical assessments were made by the Positive and Negative Syndrome Scale at the beginning and end of each treatment period. RESULTS: In intention-to-treat analysis, lamotrigine treatment was more effective in reducing positive (effect size.7, p =.009) and general psychopathological (effect size.6, p =.030) symptoms, whereas no improvement was observed in negative symptoms. CONCLUSIONS: These results provide the first evidence from a randomized controlled trial of an effective pharmacological treatment with an anticonvulsant agent in treatment-resistant schizophrenia and indicate that both positive and general psychopathological symptoms in patients with schizophrenia can be controlled by a drug that is not a dopamine antagonist. The results are in line with previous experimental data suggesting that excessive glutamate neurotransmission contributes to the positive symptoms of schizophrenia.     

SIESTA - Home sleep study with BresoDx for obstructive sleep apnea: a randomized controlled trial

Study objectivesThe objectives of this study were to evaluate (1) the accuracy of the clinical diagnosis of obstructive sleep apnea (OSA) informed by the home sleep study with a Type 4 portable monitor BresoDx® versus Type 1 polysomnography (PSG); and (2) agreement of the apnea-hypopnea index (AHI) compared between BresoDx and PSG.Material and methodsThis was a randomized, parallel, multicentre, single-blind, pragmatic controlled trial enrolling adults referred to three Ontario sleep clinics for suspected OSA. Participants were randomized to BresoDx followed by PSG (one-night apart) or PSG followed by BresoDx sleep testing sequence arms. The primary outcomes included the accuracy of clinical diagnosis and OSA severity measured by AHI between tests.ResultsIn sum, 233 participants completed both sleep studies and 206 completed physician consultation visits. The agreement between clinical diagnosis informed by PSG versus BresoDx was fair (Cohen's kappa coefficient = 0.28). The sensitivity of BresoDx-informed clinical diagnosis against PSG was between 0.86 and 0.89, and the specificity between 0.38 and 0.44. For AHI cut-off of ≥5 events/hour the sensitivity, specificity and positive and negative predictive values were 0.85, 0.48, 0.81 and 0.54.ConclusionsHome sleep apnea testing with BresoDx can be used in a referral population with a high pretest probability of OSA similar to other Type IV devices. This study complements the existing body of evidence suggesting that home testing with portable devices plays a valuable role for diagnosing of OSA in a variety of settings.SIESTA trial registrationwww.clinicaltrials.gov (Identifier: NCT02003729).     

Improved sleep continuity and increased slow wave sleep and REM latency during ziprasidone treatment: a randomized, controlled, crossover trial of 12 healthy male subjects

OBJECTIVE: Ziprasidone, an atypical antipsychotic, is a potent dopamine (D(2)) and serotonin (5-HT(2A/C)) receptor blocker, has agonistic properties at the 5-HT(1A) receptor, and blocks serotonin and norepinephrine reuptake. These transmitter systems are closely related to the regulation of sleep. METHOD: The aim of this double-blind, placebo-controlled, randomized, crossover study was to investigate the effects of ziprasidone on polysomnographic sleep structure and subjective sleep quality. Twelve healthy male subjects were randomly assigned to receive ziprasidone 40 mg or placebo for 2 sessions each composed of 2 consecutive nights (night 1, standard sleep conditions; night 2, acoustic stress) 5 days apart. Treatment was administered orally 2 hours before bedtime. The study was conducted from April 2004 to July 2004. RESULTS: Ziprasidone significantly increased total sleep time, sleep efficiency, percentage of sleep stage 2, and slow wave sleep; decreased the number of awakenings; and significantly affected tonic and phasic REM sleep parameters, i.e., it decreased percentage of REM and REM density and profoundly increased REM latency. CONCLUSION: Ziprasidone's effects on the sleep profile are somehow opposite to what is known about sleep of depressed patients (e.g., disturbances of sleep continuity, a reduciton of slow wave sleep, and a disinhibition of REM sleep). Its REM sleep-suppressing properties resemble those of most, although not all, antidepressants and may be clinically relevant. The drug also demonstrates sleep-consolidating properties under both standard routine and acoustic stress conditions. These effects are most likely related to ziprasidone's 5-HT(2C) antagonism, 5-HT(1A) agonism, and serotonin and norepinephrine reuptake inhibition.     

Intensive case management in Australia: a randomized controlled trial.

This study compared intensive case management (ICM) with standard clinical case management in a well-resourced community mental health service in Australia. A total of 73 severely disabled clients of an existing clinical service were randomly allocated to either ICM (caseload 10 clients per clinician) or standard case management (caseload up to 30 clients per clinician) and followed up for 12 months. A greater proportion of clients receiving ICM showed improved social functioning, these clients had fewer psychiatric hospital admissions involving police, and were more likely to engage and remain in treatment compared to those who received standard case management. Clients receiving ICM did not show a reduction in hospitalization duration or total number of episodes. It is suggested that future studies of ICM should focus on which aspects of treatment produce positive outcomes, how they can be applied to routine clinical settings, and over what period of time outcomes are sustained.     

A randomized double-blind fluvoxamine/placebo crossover trial in pathologic gambling.

BACKGROUND: The study assessed the efficacy and tolerability of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine in the treatment of pathologic gambling (PG). METHODS: A 16-week randomized double-blind crossover design insured that each subject received 8 weeks of fluvoxamine and 8 weeks of a placebo. Fifteen patients entered and 10 subjects, all male, completed the study. RESULTS: Fluvoxamine resulted in a significantly greater percent improvement in overall gambling severity on the PG Clinical Global Impression (PG-CGI) scale. There was a significant drug effect on gambling urge and behavior as measured by the PG modification of the Yale-Brown Obsessive Compulsive Scale and PG-CGI scale improvement scores; however, there was a significant interaction of drug effect with the order of administration of drug and placebo. Post hoc analysis, treating each phase as a separate trial, demonstrated a significant difference between fluvoxamine and the placebo in the second phase of the trial but not in the first. Fluvoxamine side effects were of only mild intensity and consistent with SSRI treatment and were not associated with early withdrawal from the study. CONCLUSIONS: These findings suggest that fluvoxamine is well tolerated and may be effective in the treatment of PG in an acute trial, and that an early placebo effect in PG treatment appears to diminish over time. To confirm this finding and to determine whether improvement persists over an extended period of time, a longer duration parallel-design trial with long-term maintenance follow-up should be conducted in a larger and more diverse PG population.     

Use of a self-help book with weekly therapist contact to reduce tinnitus distress: a randomized controlled trial

OBJECTIVE: Tinnitus distress can be reduced by means of cognitive-behavior therapy (CBT). To compensate for the shortage of CBT therapists, we aimed, in this study, to investigate the effects of a CBT-based self-help book guided by brief telephone support. METHODS: Seventy-two patients were randomized either to a self-help book and seven weekly phone calls or to a wait-list control condition, later on receiving the self-help book with less therapist support. The dropout rate was 7%. Follow-up data 1 year after completion of treatment were also collected (12% dropout). The Tinnitus Reaction Questionnaire (TRQ) was the main outcome measure, complemented with daily ratings of tinnitus and measures of insomnia, anxiety, and depression. RESULTS: On the TRQ, significant reductions were found in the treatment group both immediately following treatment and at 1-year follow-up. In the treatment group, 32% reached the criteria for clinical significance (at least 50% reduction of the TRQ) compared to 5% in the wait-list group. Directly after treatment, two out of five measures showed significant differences in favor of the treatment with more therapist support compared with the group who, after their waiting period, received little therapist support. The self-help treatment was estimated to be 2.6 (seven phone calls) and 4.8 (one phone call) times as cost-effective as regular CBT group treatment. CONCLUSIONS: Guided self-help can serve as an alternative way to administer CBT for tinnitus. Preliminary results cast some doubts on the importance of weekly therapist contact. The effect size was somewhat smaller than for regular CBT, but on the other hand, the self-help seems far more cost-effective. Future studies should compare treatment modalities directly and explore cost-effectiveness more thoroughly.     

Treatment of sleep apnea in chronic heart failure patients with auto-servo ventilation improves sleep fragmentation: a randomized controlled trial

BackgroundImpaired sleep efficiency is independently associated with worse prognosis in patients with chronic heart failure (CHF). Therefore, a test was conducted on whether auto-servo ventilation (ASV, biphasic positive airway pressure [BiPAP]–ASV, Philips Respironics) reduces sleep fragmentation and improves sleep efficiency in CHF patients with central sleep apnea (CSA) or obstructive sleep apnea (OSA).MethodsIn this multicenter, randomized, parallel group trial, a study was conducted on 63 CHF patients (age 64 ± 10 years; left ventricular ejection fraction 29 ± 7%) with CSA or OSA (apnea–hypopnea Index, AHI 47 ± 18/h; 46% CSA) referred to sleep laboratories of the four participating centers. Participants were randomized to either ASV (n = 32) or optimal medical treatment alone (control, n = 31).ResultsPolysomnography (PSG) and actigraphy at home (home) with centralized blinded scoring were obtained at baseline and 12 weeks. ASV significantly reduced sleep fragmentation (total arousal index_PSG: −16.4 ± 20.6 vs. −0.6 ± 13.2/h, p = 0.001; sleep fragmentation index_home: −7.6 ± 15.6 versus 4.3 ± 13.9/h, p = 0.003, respectively) and significantly increased sleep efficiency assessed by actigraphy (SE_home) compared to controls (2.3 ± 10.1 vs. −2.1 ± 6.9%, p = 0.002). Effects of ASV on sleep fragmentation and efficiency were similar in patients suffering from OSA and CSA.ConclusionsAt home, ASV treatment modestly improves sleep fragmentation as well as sleep efficiency in CHF patients having either CSA or OSA.     

Neurofeedback in ADHD: a single-blind randomized controlled trial

Neurofeedback treatment has been demonstrated to reduce inattention, impulsivity and hyperactivity in children with attention deficit/hyperactivity disorder (ADHD). However, previous studies did not adequately control confounding variables or did not employ a randomized reinforcer-controlled design. This study addresses those methodological shortcomings by comparing the effects of the following two matched biofeedback training variants on the primary symptoms of ADHD: EEG neurofeedback (NF) aiming at theta/beta ratio reduction and EMG biofeedback (BF) aiming at forehead muscle relaxation. Thirty-five children with ADHD (26 boys, 9 girls; 6–14 years old) were randomly assigned to either the therapy group (NF; n = 18) or the control group (BF; n = 17). Treatment for both groups consisted of 30 sessions. Pre- and post-treatment assessment consisted of psychophysiological measures, behavioural rating scales completed by parents and teachers, as well as psychometric measures. Training effectively reduced theta/beta ratios and EMG levels in the NF and BF groups, respectively. Parents reported significant reductions in primary ADHD symptoms, and inattention improvements in the NF group were higher compared to the control intervention (BF, d _corr = −.94). NF training also improved attention and reaction times on the psychometric measures. The results indicate that NF effectively reduced inattention symptoms on parent rating scales and reaction time in neuropsychological tests. However, regarding hyperactivity and impulsivity symptoms, the results imply that non-specific factors, such as behavioural contingencies, self-efficacy, structured learning environment and feed-forward processes, may also contribute to the positive behavioural effects induced by neurofeedback training.     

Sleep promotion program for improving sleep behaviors among adolescents in selected schools: a randomized controlled trial

Study objectives: The present study evaluated the efficacy of sleep promotion program (SPP) on sleep hygiene practices, sleep quality, daytime sleepiness, and present functioning among adolescents. Methods: A two-arm, parallel, cluster randomized controlled trial was adopted. Participants were 660 adolescents aged 11–17(330 each in the intervention and control group). A socio-demographic questionnaire with sleep and activity items along with standardized questionnaires was used. Results: Significant improvements were observed in the experimental group after the intervention in the sleep hygiene practices, overall sleep quality and its sub-components like subjective sleep quality, sleep latency, and sleep efficiency at 2 weeks, and daytime sleepiness at 6 weeks. Other sleep quality components such as sleep duration, sleep disturbance, daytime dysfunction, and the present functioning compared did not statistically differ from the control group. Statistically significant positive correlations were observed between the target sleep variables. Sleep hygiene tends to deteriorate with higher grade level of adolescents, whereas sleep quality, sleep duration, and daytime sleepiness became worse with higher age and grade level. Conclusions: SPP holds a promise for improving healthy adolescents sleep behaviors. Interventions to improve emotional health could be explored in the future.     

The impact of social skills training for social anxiety disorder: A randomized controlled trial

ObjectiveSocial anxiety disorder (SAD) impacts social, occupational and academic functioning. Although many interventions report change in social distress, improvement in social behavior remains under-addressed. This investigation examined the additive impact of social skills training (SST) for the treatment of SAD.MethodUsing a sample of 106 adults who endorsed SAD across numerous social settings, participants were randomized to exposure therapy (imaginal and in vivo) alone, a combination of SST and exposure therapy known as Social Effectiveness Therapy (SET), or a wait list control. The assessment strategy included self-report measures, blinded clinical ratings and blinded assessment of social behavior.ResultsBoth interventions significantly reduced distress in comparison to the wait list control and at post-treatment, 67% of patients treated with SET and 54% of patients treated with exposure therapy alone no longer met diagnostic criteria for SAD, a difference that was not statistically significant. When compared to exposure therapy alone, SET produced superior outcomes (p < .05) on measures of social skill and general clinical status. In addition to statistical significance, participants treated with SET or exposure reported clinically significant decreases on two measures of self-reported social anxiety and several measures of observed social behavior (all ps < .05).ConclusionsBoth interventions produced efficacious treatment outcome, although SET may provide additional benefit on measures of social distress and social behavior.     

Mindfulness-based therapy in adults with an autism spectrum disorder: A randomized controlled trial

Research shows that depression and anxiety disorders are the most common psychiatric concern in autism spectrum disorders (ASD). Mindfulness-based therapy (MBT) has been found effective in reducing anxiety and depression symptoms, however research in autism is limited. Therefore, we examined the effects of a modified MBT protocol (MBT-AS) in high-functioning adults with ASD. 42 participants were randomized into a 9-week MBT-AS training or a wait-list control group. Results showed a significant reduction in depression, anxiety and rumination in the intervention group, as opposed to the control group. Furthermore, positive affect increased in the intervention group, but not in the control group. Concluding, the present study is the first controlled trial to demonstrate that adults with ASD can benefit from MBT-AS.     

Mindfulness-based therapy in adults with an autism spectrum disorder: A randomized controlled trial

Research shows that depression and anxiety disorders are the most common psychiatric concern in autism spectrum disorders (ASD). Mindfulness-based therapy (MBT) has been found effective in reducing anxiety and depression symptoms, however research in autism is limited. Therefore, we examined the effects of a modified MBT protocol (MBT-AS) in high-functioning adults with ASD. 42 participants were randomized into a 9-week MBT-AS training or a wait-list control group. Results showed a significant reduction in depression, anxiety and rumination in the intervention group, as opposed to the control group. Furthermore, positive affect increased in the intervention group, but not in the control group. Concluding, the present study is the first controlled trial to demonstrate that adults with ASD can benefit from MBT-AS.     

Effects of armagnac or vodka on platelet aggregation in healthy volunteers: a randomized controlled clinical trial

BACKGROUND: Cardiovascular mortality is especially low in southwest France (the French Paradox). In previous experimental studies, we found that alcohol-free extracts of armagnac could inhibit human platelet function in vitro and experimental thrombosis in vivo. To test the possible relevance of these findings, we tested the effects of daily use of small quantities of armagnac against same alcohol strength, polyphenol-free vodka in healthy volunteers. METHOD: Randomized controlled trial comparing 5-year old armagnac (30 ml/day for 2 weeks) to same alcoholic strength vodka, in 20 healthy volunteers, on platelet aggregation induced by ADP, collagen, and thrombin, as well as bleeding time, partial thromboplastin time (pTT), and plasma lipids during and after consumption. Platelet testing was done blind. RESULTS: After 14 days, ADP-induced platelet aggregation was inhibited more in armagnac (-31+/-3.2% compared to pretreatment values, p<.01) than in vodka (-11.0+/-6.8%, NS) users (p<.05, armagnac vs. vodka). A rebound increase of aggregation was found 2 weeks later in vodka but not in armagnac users. The same pattern was found for thrombin-induced aggregation, including post-treatment rebound. No effect was found on collagen-induced aggregation, bleeding time, pTT, or plasma lipids. CONCLUSION: The chronic ingestion of moderate quantities of armagnac modified platelet aggregation to ADP in healthy volunteers. The difference with the effects of same alcohol degree vodka is in favour of an effect of the nonalcoholic fraction in the effects of armagnac, rather than just alcohol. All spirits may not be equal for cardioprotection.     

Reduced glutathione in amyotrophic lateral sclerosis: an open, crossover, randomized trial

The present study set out to define the possible effect of reduced glutathione (GSH), the substrate of glutathione peroxidase (GSH-Px), a free radical inactivating enzyme, in amyotrophic lateral sclerosis (ALS). Thirty-two patients affected by definite ALS seen in our institution between August 1993 and July 1994 were admitted to the study. The effect of GSH was studied in an open, crossover, randomized study. GSH was given at the dose of 600 mg each day intramuscularly for 12 weeks. The patients, taken sequentially, were randomly assigned to two groups. The first group received the drug while the second received only symptomatic therapies for 12 weeks. After a week of wash-out, the second group received GSH and the first only symptomatic therapies for 12 weeks. The rate of progression of the diseases was compared in the two groups. Clinical evaluation included manual test for muscle strength, Norris scale, bulbar scale, and forced vital capacity (FVC) percent. No significant difference was found in the progression of ALS in the two periods, although a slight slowing of the disease progression rate was found during the period of treatment, probably related to the open design of the study. Our data do not show any significant effect of reduced glutathione in modifying the progression of ALS.

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Sommario Lo scopo del lavoro è stato definire il possibile effetto del glutatione ridotto (GSH), il substrato della glutatione perossidasi (GSH-Px), un enzima inattivatore dei radicali liberi, nella sclerosi laterale amiotrofica (SLA). Sono stati ammessi nello studio 32 pazienti affetti da SLA definita visitati nel nostro Istituto dall'agosto 1993 a luglio 1995. L'effetto del GSH è stato studiato in uno studio in aperto, crossover, randomizzato. Il GSH è stato somministrato alla dose di 600 mg per via intramuscolare per 12 settimane. I pazienti sono stati assegnati a caso, secondo l'ordine di visita, a due gruppi. Per le prime 12 settimane il primo gruppo ha ricevuto il farmaco e il secondo solo terapie sintomatiche. Dopo un wash-out di una settimana, il secondo gruppo ha ricevuto il GSH e il primo solo terapie sintomatiche per altre 12 settimane. è stata confrontata la velocità di progressione dei sintomi nei due gruppi. La valutazione clinica comprendeva test manuali per la forza muscolare, la scala di Norris, una scala bulbare e la capacità vitale forzata (FVC). Non è stata trovata alcuna differenza significativa nella velocità di progressione della SLA nei due periodi, anche se è stato osservato un lieve rallentamento nella velocità di progressione durante il perrodo di trattamento, forse dovuto al disegno in aperto dello studio. I nostri dati non dimostrano alcun effetto significativo del glutatione ridotto nel modificare la progressione della SLA.