The prevalence and characteristics of patients with classic locked-in syndrome in Dutch nursing homes.

To establish the point prevalence and characteristics of patients with locked-in syndrome (LIS), particularly of the classic type, residing in Dutch nursing homes, a cross-sectional survey of Dutch nursing homes was conducted. The classic form of LIS was defined according to the criteria of the American Congress of Rehabilitation Medicine (1995). All Dutch long-term care organisations (n = 187) were asked if they had any patients with classic LIS as of December 5, 2011. The treating Elderly Care Physicians were then contacted to provide patient characteristics. Of all organisations, 91.4% responded, and 11 organisations reported a total of 12 patients. After analysing the questionnaires, it was determined that ten patients had LIS, and two patients were characterised with vegetative state. Only two patients met the criteria for classic LIS, while six patients showed partial LIS. One of these patients was admitted to the nursing home after December 5, 2011, and was therefore, excluded. LIS without accompanying pontine lesion was observed in the remaining two patients. For the first time, the prevalence of classic LIS has been established at 0.7/10,000 somatic nursing home beds in all Dutch long-term care organisations. Possible explanations for this low prevalence could be the Dutch provision of home care or the influence of end-of-life decisions, such as euthanasia and withholding or withdrawing all medical treatment, including artificial nutrition and hydration. These alternate outcomes should be explored in further studies.

Treatment of atypical depression: post-hoc analysis of a randomized controlled study testing the efficacy of sertraline and cognitive behavioural therapy in mildly depressed outpatients.

OBJECTIVE: Atypical features are common among depressed primary care patients, but clinical trials testing the efficacy of psychopharmacological and/or psychotherapeutic treatment are lacking. This paper examines the efficacy of sertraline and cognitive behavioural therapy (CBT) among depressed patients with atypical features. SUBJECTS AND METHODS: Analyses involve a double-blind comparison of sertraline versus placebo (N=47) and a single-blind comparison between CBT versus a guided self-help group (GSG) (N=48), with primary efficacy endpoints being the Inventory of Depressive Symptomatology (IDS(C)) and Hamilton Depression Scale (HAMD-17). RESULTS: In intent-to-treat (ITT) analyses, the decrease on the IDS(C) scale (and HAMD-17) was greater after CBT compared to GSG: p=0.01 (HAMD-17: p=0.01). The difference between selective serotonin reuptake inhibitors (SSRI) versus placebo was not significant: p=0.22 (HAMD-17: p=0.36). LIMITATIONS: The number of cases in each treatment group was small, thereby limiting statistical power. Patients medicated with sertraline were 10 to 15 years younger than those included in the other groups of treatment. CONCLUSIONS: CBT may be an effective alternative to GSG for mildly depressed patients with atypical features. Although SSRI were not superior to placebo, it would be premature to rule out SSRI as efficacious in atypical depression.

A Dutch case of a takotsubo cardiomyopathy after pacemaker implantation.

An 83-year-old female patient with symptomatic atrial fibrillation was referred to the Department of Cardiology for a scheduled electrocardioversion. Because of a junctional escape rhythm after the electrocardioversion she received a DDD pacemaker which was complicated by dyspnoea and ST-segment elevations in the inferior and precordial leads. Because of suspicion of an acute myocardial infarction she was transferred to a PCI centre. The coronary angiogram showed no abnormalities. In the initial phase, an echocardiogram was performed. The echocardiogram showed apical akinesis and a reduced left ventricular function. During follow-up left ventricular function improved and was completely normal nine weeks after the event. The clinical picture was interpreted as a takotsubo cardiomyopathy after a pacemaker implantation. (Neth Heart J 2009;17:487-90.).

Cognitive behavioural group therapy to improve patients' strategies for coping with restless legs syndrome: a proof-of-concept trial.

BACKGROUND: Restless legs syndrome (RLS) is a usually chronic disorder accompanied by clinically relevant psychosocial impairment. To date, no psychologically based approach is available to improve the coping strategies and quality of life of RLS sufferers. OBJECTIVE: To develop cognitive behavioural therapy tailored to this disorder (the RELEGS coping therapy programme) and present the results of this proof-of-concept study. METHODS: Twenty-five patients (five men, 20 women; 15 medicated, 10 unmedicated; mean (SD) age 56.1 (12.3) years) with subjective psychosocial impairment due to RLS participated in one of three consecutive therapy groups. The severity scales (IRLS and RLS-6) indicated moderate to severe RLS symptoms at baseline. Exclusion criteria were secondary RLS, foreseeable change of RLS medication during the study period, serious physical or psychiatric comorbidity, and severe cognitive deficits. Each group took part in eight group sessions (90 min each with a break). RESULTS: At the end of the treatment, both the RLS-related quality of life and the mental health status of the subjects had improved significantly (QoL-RLS scale: from 28.6 (12.8) to 23.4 (13.1); SCL-90-R: from 51.3 (37.0) to 45.9 (32.9)). The improvement remained at follow-up 3 months later. Subjective ratings of RLS severity had improved at the end of therapy and at follow-up. Psychometric scales not specific for RLS-related impairment remained unaffected by the treatment. CONCLUSIONS: The study establishes the feasibility and high acceptance of the newly devised therapy programme. The application of RLS-oriented specific psychological strategies is a step toward an integrated treatment approach in RLS.

Comparison of Hypericum extract WS 5570 and paroxetine in ongoing treatment after recovery from an episode of moderate to severe depression: results from a randomized multicenter study.

OBJECTIVE: To test and compare the efficacy and safety of Hypericum extract WS 5570 to paroxetine, a potent SSRI, in patients suffering from moderate or severe depression according to DSM-IV criteria. METHODS: In a multicenter, randomized, double-blind phase III study, the changes in moderate to severe major depression DSM-IV; 17-item Hamilton Depression Rating Scale (HAM-D total>or=22) after an acute treatment with Hypericum extract WS 5570 or paroxetine were analyzed in a 16-week continuation phase for relapse prevention. Patients with a HAM-D total score decrease of >or=50% during the 6 weeks of acute treatment were asked to continue the treatment for another 4 months. One-hundred and thirty-three adult out-patients who received maintenance doses of 900 (n=33) or 1800 mg/d (n=38) of WS 5570 and 20 (n=28) or 40 mg/d (n=34) of paroxetine, respectively, were included. The relevant dosage was already fixed during the acute treatment. RESULTS: Between baseline of the acute phase and end of continuation treatment the HAM-D total score decreased from 25.3+/-2.5 (mean+/-SD) to 4.3+/-6.2 points for WS 5570 and from 25.3+/-2.6 to 5.2+/-5.5 points for paroxetine (p=0.49, two-sided t-test; median relative decrease: 92.0 and 85.5%, respectively). During maintenance treatment alone (day 154-day 42), 61.6% of the patients randomized to WS 5570 and 54.6% treated with paroxetine showed an additional reduction (p=0.59) with respect to the HAM-D total score. Remission (HAM-D endpoint total score below 8) occurred in 81.6% (31 patients) of the patients for WS 5570 and in 71.4% (30 patients) for paroxetine (p=0.29). Three patients in the WS 5570 group and 2 patients in the paroxetine group showed a HAM-D increase>5 points during continuation treatment. In the continuation phase there were 0.006 adverse events per day of exposure for WS 5570 and 0.007 events for paroxetine. CONCLUSION: This study showed that WS 5570 and paroxetine were similarly effective in preventing relapse in a continuation treatment after recovery from an episode of moderate to severe depression and point therefore to an important alternative treatment option for long-term relapse-prevention.

[Shared decision-making with hypertensive patients. Results of an implementation in Germany]. / "Shared Decision-Making" mit Bluthochdruckpatienten. Ergebnisse einer Implementierung in Deutschland.

BACKGROUND AND OBJECTIVE: Lack of compliance is a common problem in the treatment of hypertension. Ineffective physician-patient-communication and a lack of patients involvement can play a crucial role. We tested the hypothesis that shared decision-making (SDM) results in higher involvement of patients in their blood pressure lowering therapy and evaluated the effects of SDM on the control of blood pressure. PATIENTS AND METHODS: Two groups of 84 hypertensives were compared: an intervention group (26 women and 13 men, age 61 +/- 10 years) treated by 15 specially SDM-trained primary care physicians, and a control group of 45 hypertensives. All 84 patients were enrolled in a patient education programme. Changes of blood pressure were assessed after one year by self-measurements. Questionnaires about their attitude to patient autonomy, the SDM process, quality of life, physician-patient-relationship and life-style changes were analysed as well. RESULTS: After one year the blood pressure had decreased in both the intervention group (-9.26 +/- 10.2/-5.3 +/- 9.5 mmHg, p < 0.001) and in the control group (-6.0 +/- 11.8/-3.0 +/- 8.3 mmHg, p < 0.05), without a significant difference between the two groups. Among a subgroup of patients with a marked preference for SDM there was a close correlation between an increase of SDM and a decrease in systolic blood pressure (p = 0.016). Also, the numbers of antihypertensive drugs increased more in the intervention group (p = 0.022) than in control patients. Furthermore, increase in knowledge about hypertension and its treatment was greater in the intervention group (P=0.006). CONCLUSION: Implementation of SDM had a significant effect on systolic blood pressure control only in the subgroup of patients with marked preference for SDM. Thus, the identification of patients with a preference for SDM may improve blood pressure control and their adherence to the prescribed drug therapy.

[Bibrocathol eye ointment is efficacious in blepharitis. Results from a randomized, double-blind, controlled clinical trial]. / Bibrocathol-Augensalbe ist wirksam bei Blepharitis. Ergebnisse einer randomisierten, doppelblinden, kontrollierten klinischen Studie.

Bibrocathol (Noviform) 5% ointment is a frequently used therapy for blepharitis. The study included 197 patients who were randomized to be treated over 2 weeks with bibrocathol or an ointment vehicle, respectively. Slit lamp examinations were performed on day 1 (baseline) and day 14 (end of study) to assess lid edema, lid erythema, debris, and pouting of Meibomian glands; patients rated their subjective complaints. Bibrocathol was superior to the control treatment in improving the sum score of the 5 scales (by 7.0 vs 4.7 points, p<0.001), especially in patients with primarily severe symptoms (by 8.3 vs 4.8, p<0.0001). Antiseptic therapy with bibrocathol eye ointment 3 times daily over 2 weeks was found to be efficacious in the treatment of acute forms of blepharitis which do not require antibiotic therapy. Bibrocathol treatment is well tolerated and safe.

Efficacy of cabergoline in restless legs syndrome: a placebo-controlled study with polysomnography (CATOR).

OBJECTIVE: To assess the efficacy and safety of the dopamine agonist cabergoline in the treatment of patients with idiopathic restless legs syndrome (CATOR study). METHODS: Patients with moderate to severe restless legs syndrome (RLS) were randomly assigned to cabergoline (single evening dose: 2 mg) or placebo and treated for 5 weeks in a double-blind, multicenter polysomnography (PSG) trial. The primary efficacy measures were the periodic leg movements during sleep arousal index (PLMS-AI) and sleep efficiency. These and further PSG variables were monitored by centrally evaluated PSG. Severity of RLS was assessed using the International RLS Study Group Severity Scale (IRLS), the RLS-6 scales, the Sleep Questionnaire Form A (SF-A; quality of sleep), and the Quality of Life for RLS questionnaire. RESULTS: Forty-three patients were treated and 40 patients were evaluated with PSG (age 56 +/- 10 years, 73% women). Cabergoline was superior to placebo in terms of the PLMS-AI (-17.7 +/- 16.4 vs -4.5 +/- 20.0 placebo; p = 0.0024), sleep efficiency (+6.2 +/- 13.9% vs +3.3 +/- 11.7%; p = 0.0443), PLMS index (p = 0.0014), PLM index (p = 0.0012), and total sleep time (p = 0.0443). Improvements in IRLS total score (-23.7 +/- 11.2 vs -7.9 +/- 11.0 placebo; p = 0.0002), RLS-6 severity scales during the night (p = 0.0010) and during the day (p = 0.0018), Clinical Global Impressions severity item (p = 0.0003), sleep quality (p = 0.0180), SF-A sleep quality (p = 0.0371), and QoL-RLS (p = 0.0247) were larger in patients treated with cabergoline compared with the placebo group. Adverse events were only mild and well-known side effects of dopamine agonists. CONCLUSION: Single-evening cabergoline is an efficacious and well-tolerated short-term therapy for sensorimotor symptoms of restless legs syndrome and associated sleep disturbances.

Lisuride treatment of restless legs syndrome: first studies with monotherapy in de novo patients and in combination with levodopa in advanced disease.

In two 4-week polysomnography pilot studies with 10 patients each, we investigated the efficacy of oral lisuride as monotherapy in de novo RLS patients as well as in combination with levodopa in advanced RLS. Daily doses at study end were 0.3 mg lisuride, plus 150 mg levodopa in the combination study. Marked improvements occurred in both studies in different PLM indexes and in the CGI. Levodopa dose could be decreased by 27%. Lisuride might be an efficacious treatment for RLS in general, and in combination with levodopa in advanced stage.

Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine.

OBJECTIVE: To investigate the efficacy of hypericum extract WS 5570 (St John's wort) compared with paroxetine in patients with moderate to severe major depression. DESIGN: Randomised double blind, double dummy, reference controlled, multicentre non-inferiority trial. SETTING: 21 psychiatric primary care practices in Germany. PARTICIPANTS: 251 adult outpatients with acute major depression with total score > or = 22 on the 17 item Hamilton depression scale. INTERVENTIONS: 900 mg/day hypericum extract WS 5570 three times a day or 20 mg paroxetine once a day for six weeks. In initial non-responders doses were increased to 1800 mg/day hypericum or 40 mg/day paroxetine after two weeks. MAIN OUTCOME MEASURES: Change in score on Hamilton depression scale from baseline to day 42 (primary outcome). Secondary measures were change in scores on Montgomery-Asberg depression rating scale, clinical global impressions, and Beck depression inventory. RESULTS: The Hamilton depression total score decreased by mean 14.4 (SD 8.8) points, corresponding to 56.6% (SD 34.3%) of the baseline value, in the hypericum group and by 11.4 (SD 8.6) points (44.8% (SD 33.5%) of baseline value) in the paroxetine group (intention to treat analysis; similar results were observed in the per protocol analysis). The intention to treat analysis (lower one sided 97.5% confidence limit 1.5 points for the difference hypericum minus paroxetine) and the per protocol analysis (lower confidence limit 0.7 points) showed non-inferiority of hypericum and statistical superiority over paroxetine. The lower limits in both cases exceeded the pre-specified non-inferiority margin of -2.5 points and the superiority margin of 0. The incidence of adverse events was 0.035 and 0.060 events per day of exposure for hypericum and paroxetine, respectively. CONCLUSIONS: In the treatment of moderate to severe major depression, hypericum extract WS 5570 is at least as effective as paroxetine and is better tolerated.

Fluoxetine versus trimipramine in the treatment of depression in geriatric patients.

INTRODUCTION: Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), and trimipramine, a tricyclic antidepressant (TCA), were compared in terms of efficacy and tolerability in a six-week, parallel group, double-blind pilot study in 41 geriatric patients with major depression (61 - 85 years old). METHOD: The Hamilton Rating Scale for Depression (HAMD-17), the Montgomery-Asberg Rating Scale (MADRS), the Adjective Mood Scale (Bf-S), the Clinical Global Impression (CGI), and the Patients Global Impression (PGI) were used to measure changes in depressive symptoms. RESULTS: Improvement with treatment was found on all scales. Efficacy and tolerability were similar in both groups. No statistically significant differences were found. CONCLUSION: These findings suggest that fluoxetine and trimipramine are comparable in terms of efficacy and tolerability in the treatment of major depression in geriatric patients.

The catechol-O-methyltransferase Val108/158Met polymorphism affects short-term treatment response to mirtazapine, but not to paroxetine in major depression.

The catechol-O-methyltransferase (COMT) is a major degrading enzyme in the metabolic pathways of catecholaminergic neurotransmitters such as dopamine and norepinephrine. This study investigated whether the functionally relevant Val(108/158)Met gene variant is associated with differential antidepressant response to mirtazapine and/or paroxetine in 102 patients with major depression (DSM-IV criteria) participating in a randomized clinical trial with both drugs. In patients treated with mirtazapine, but not paroxetine, allelic variations in the COMT gene were associated with differential response. COMT(VAL/VAL) and COMT(VAL/MET) genotype carriers showed a better response than COMT(MET/MET)-bearing patients in the mirtazapine group. Moreover, carriers of the COMT(VAL/VAL) or COMT(VAL/MET) genotype had significantly greater HAMD-17 (Hamilton Rating Scale for Depression 17 item version) score reductions than COMT(MET/MET) homozygotes from week 2 to 6, respectively, in the mirtazapine group. Time course of response and antidepressant efficacy of mirtazapine, but not paroxetine, seem to be influenced in a clinically relevant manner by this allelic variation within the COMT gene.

Effective cabergoline treatment in idiopathic restless legs syndrome.

OBJECTIVE: To assess the efficacy and safety of the dopamine agonist cabergoline (CAB) in patients with restless legs syndrome (RLS). METHODS: Patients with moderate to severe RLS were randomized into four groups receiving placebo, 0.5 mg, 1 mg, or 2 mg CAB once daily in a double-blind, placebo-controlled, multicenter dose-finding trial followed by an open long-term extension trial of 47 weeks. Efficacy was assessed with the RLS-6 scales and International RLS Study Group severity scale (IRLS). RESULTS: A total of 85 patients (age 56 +/- 10 years, 71% females) were treated. Severity of RLS-6 scale symptoms during the night (the primary endpoint) was markedly improved by all CAB doses compared to placebo (placebo: -1.4 +/- 3.1, 0.5 mg CAB: -4.2 +/- 3.0 [p = 0.0082], 1.0 mg CAB: -4.0 +/- 2.9 [p = 0.0040], 2.0 mg CAB: -4.8 +/- 3.7 [p = 0.0026]). Similar results were found for the RLS severity at bedtime and during the day, IRLS, and satisfaction with sleep. A stable, clinically relevant improvement was achieved in all efficacy measures (severity during the night: change between last assessment and baseline: -5.6 +/- 2.5, rate of remission: 71.2%) throughout 1 year with a mean CAB dose of 2.2 mg per day. During long-term treatment, 6 of 66 treated patients were affected (n = 2) or possibly affected (n = 4) by mild augmentation. Under CAB therapy up to 1 year, 11 of 85 patients discontinued treatment due to a drug-related adverse event. CONCLUSIONS: Cabergoline is an efficacious and well-tolerated option for the treatment of restless legs symptoms during the night and the day.

The assessment of vegetative and functional symptoms in fibromyalgia patients: the tropisetron experience.

Vegetative and functional symptoms are, besides pain and tenderness of tender points, considered as additional information for the diagnosis of fibromyalgia (FM). In clinical trials, vegetative and functional symptoms have been included for selection of patients (e.g. sleep disturbances) and as secondary outcome parameters. Despite the relevance of these symptoms, no validated method is currently available but symptom lists are ad hoc developed by investigators. In this manuscript, data from a published double blind, randomised study are reanalysed which compared oral therapy over 10 days with 5 mg, 10 mg, and 15 mg to placebo in FM patients. This study applied a list of 17 vegetative and functional symptoms, which had to be scored by the patients by use of a 4-point severity scale (0 = none to 3 = severe). Factor analysis of the baseline data from 195 patients suggested to separate 6 sub-scales: Cardiovascular, gastrointestinal, psychiatric (sleep disturbance), nervous, autonomic system, and general disorders. Sleep disturbances, general symptoms (morning stiffness, fatigue) and autonomic symptoms (cold extremities, hyperhidrosis) were most severe in intensity. Analysis of sensitivity for treatment effects made use of differences between placebo and 5 mg tropisetron in changes between baseline and final assessment of the tropisetron trial. While, on the item level, differences in favour of tropisetron could only be demonstrated for sleep disorders, on the sub-scale level, also favourable effects of tropisetron could be shown for cardiovascular and nervous system complaints and, as a tendency, for general symptoms. On the other side, the sub-scale score of gastrointestinal symptoms worsened under tropisetron whilst it improved under placebo which effect was due to side effects of the active treatment. It is concluded that symptom clusters like sub-scales of a list of vegetative and functional symptoms will be more suitable for diagnostic purposes and evaluation of treatment outcome of clinical trials. Further research is urgently required which addresses the development of a FM-specific scale to assess vegetative and functional symptoms.

Intravenous treatment of fibromyalgia with the 5-HT3 receptor antagonist tropisetron in a rheumatological practice.

In 223 fibromyalgia (FM) patients in a rheumatology practice, a follow-up postal survey was carried out 0.5-2 years after a 5-day intravenous (i.v.) treatment with 5 mg of the 5-HT3 receptor antagonist tropisetron daily on the effect of this treatment. 121 patients returned the completed questionnaire. After subtraction of 22 undeliverable questionnaires, this represented 60.2% of patients contacted for whom an assessment of the tropisetron treatment was possible. A good to very good effect of the treatment on the pain was reported by 45% of the patients, and only 25% reported an unsatisfactory effect. The effect of tropisetron IV lasted between one day and 12 weeks (mean 8.6 +/- 13.6 d). Sleep and general condition were also assessed as good or very good by almost half of the patients. The tolerance of tropisetron was generally good. In comparison with the current treatment and the best treatment with other drugs ever received, tropisetron was rated as more efficacious in almost half of the cases, though an unsatisfactory effect of tropisetron compared to other treatments was reported in 30% of the cases. Considered in comparison to less or at most equally efficacious alternatives, according to this open respective study, IV tropisetron treatment represents a promising option for the treatment of FM even though the study design incorporated many imponderables. Particularly the question of whether the success of treatment can be improved further with a longer lasting treatment or a selection of the patients still needs to be settled.

Zotepine versus placebo in the treatment of schizophrenic patients with stable primary negative symptoms: a randomized double-blind multicenter trial.

BACKGROUND: In contrast to traditional antipsychotic medication, newer, the so called atypical antipsychotic drugs promise to reduce primary negative symptoms in both, acute and chronic schizophrenia and improve quality of life. Zotepine, a D (2)5HT (2A) antagonist, was compared to placebo in this clinical trial to address these issues. METHODS: In an adaptive, 8-week multicenter, double-blind, randomized, parallel group study, efficacy and tolerability as well as influence on quality of life of zotepine and placebo were compared in 80 schizophrenic patients (53 % males, age 41 +/- 11 years) who experienced stable primary negative symptoms. Efficacy was assessed using the PANSS (primary outcome criterion: PANSS negative score), CGI, and MADRS; safety was controlled by EPS (Simpson-Angus Scale), TDRS and adverse events. Quality of life was evaluated with the SF-36 health questionnaire. RESULTS: After eight weeks of treatment with an average dose of 131 +/- 49 mg/day of zotepine, no superior efficacy of zotepine compared to placebo with respect to the PANSS subscale "negative symptoms could be demonstrated. Although patients receiving zotepine showed a pronounced reduction (per protocol set: -7.8 +/- 5.8) during treatment, it was not statistically different from a marked placebo response (-6.5 +/- 5.8). Similar small but not significant differences between zotepine and placebo were found in other subscales of the PANSS, the CGI and the MADRS. With regards to the quality of life assessment, patients under zotepine showed better results in the physical component scale and psychological well-being scale. In general, zotepine was well tolerated and there was no excess of extrapyramidal symptoms compared to placebo. CONCLUSIONS: Zotepine was not superior to placebo in reducing the severity of stable primary negative symptoms in schizophrenic patients in this trial. The main reasons for this finding were a high placebo response in a selected population, a probably too low dose of zotepine, and a short study period. However, several findings show clinical benefit of zotepine therapy in efficacy and quality of life.

Efficacy and tolerability of an ulcer compression stocking for therapy of chronic venous ulcer compared with a below-knee compression bandage: results from a prospective, randomized, multicentre trial.

OBJECTIVE: To investigate the possibility of improving healing rates in ulcus cruris venosum by using an ulcer compression stocking (U-Stocking) (Venotrain ulcertec) as compared to compression bandages. RESEARCH DESIGN AND SETTING: Prospective, multicentre, open-labelled, randomized, active-controlled study with blinded assessment of the primary endpoint. Sixteen phlebology outpatient clinics in Germany or the Netherlands or German medical practices specialized in phlebology. PATIENTS AND METHODS: 134 patients with venous leg ulcers entered the study. Among others, patients with infected ulcer or obesity were excluded. 121 patients were eligible for primary efficacy analyses. U-Stocking or bandages applied for at least eight hours per day and for up to 12 weeks. The primary endpoint was the healing rate after 12 weeks as assessed by planimetric measures. The secondary outcome variables were time to healing, changes in ulcer size (planimetry), experience of use and patient compliance. MAIN OUTCOME MEASURES: Therapy with the U-Stocking produced a significantly higher rate of complete healing of 47.5% (29/61) versus 31.7% (19/60) with bandages, 1-sided p = 0.0129 [CI: 95% for differences: 4.3% to 28.5%]. Mean time to healing was 46 days in both groups. Time required for application of the U-Stocking was a mean of 5.4 min (SD 5.4) versus 8.5 min (SD 6.5) for bandages, p = 0.0001. Around three patients in each treatment group were affected by serious adverse events. All treatment-related adverse events are known for compression therapy. CONCLUSIONS: The U-Stocking was superior to bandages in compression therapy for venous ulcer. This is of significance to new treatment standards as well as to future studies of longer term therapy (> 12 weeks) for unhealed ulcers or prevention of recurrence.

Acupuncture and Chinese herbal medicine in the treatment of patients with seasonal allergic rhinitis: a randomized-controlled clinical trial.

BACKGROUND: Patients with allergic rhinitis (AR) increasingly use complementary medicine. The aim of this study was to determine whether traditional Chinese therapy is efficacious in patients suffering from seasonal AR. METHODS: Fifty-two patients between the ages of 20 and 58 who had typical symptoms of seasonal AR were assigned randomly and in a blinded fashion to (i) an active treatment group which received a semi-standardized treatment of acupuncture and Chinese herbal medicine, and (ii) a control group which received acupuncture applied to non-acupuncture points in addition to a non-specific Chinese herbal formula. All patients received acupuncture treatment once per week and the respective Chinese herbal formula as a decoction three times daily for a total of 6 weeks. Assessments were performed before, during, and 1 week after treatment. The change in severity of hay fever symptoms was the primary outcome measured on a visual analogue scale (VAS). RESULTS: Compared with patients in the control group, patients in the active treatment group showed a significant after-treatment improvement on the VAS (P = 0.006) and Rhinitis Quality of Life Questionnaire (P = 0.015). Improvement on the Global Assessment of Change Scale was noted in 85% of active treatment group participants vs 40% in the control group (P = 0.048). No differences between the two groups could be detected with the Allergic Rhinitis Symptom Questionnaire. Both treatments were well-tolerated. CONCLUSIONS: The results of this study suggest that traditional Chinese therapy may be an efficacious and safe treatment option for patients with seasonal AR.

Pharmacokinetic-pharmacodynamic relationship of levodopa with and without tolcapone in patients with Parkinson's disease.

OBJECTIVE: To investigate the effect of administration of the catechol-Omethyltransferase (COMT) inhibitor tolcapone on the concentration-effect relationship of levodopa in patients with advanced Parkinson's disease and on-off fluctuations. DESIGN: Nonblind single-group 2-period pharmacokinetic-pharmacodynamic study. PATIENTS AND PARTICIPANTS: 12 patients, mean age 59 years, with idiopathic Parkinson's disease and response fluctuations. METHODS: The pharmacokinetics [plasma concentrations of levodopa and 3-O-methyldopa (3-OMD)] and motor effects [global score of the Columbia University Rating Scale (CURSsigma)] of levodopa (plus the peripheral decarboxylase inhibitor benserazide 1:4) were determined for 4 consecutive dosage intervals (4 hours each, starting at 8.00am) in 12 patients before (day 1) and during (day 8) coadministration of tolcapone 100 mg 3 times daily for 7 days. RESULTS: Under tolcapone, exposure to levodopa [area under the plasma concentration-time for the dosage interval (AUCt)] observed for the separate doses increased by 1.6- to 2.2-fold, and peak plasma drug concentrations (Cmax) increased by 1.1 - to 2.1 -fold. 3-OMD concentrations at day 8 were reduced to about 20% of the values at day 1. At baseline (day 1, before the first levodopa dose), CURSsigma averaged 40 +/- 10 points. After the first levodopa dose. CURSsigma declined to 20 +/- 9 points. At day 8. the predose CURSsigma decreased to a final score of 31 +/-13 points, and the maximal decline after the first levodopa dose was to a final score of 16 +/- 8 points. Population analysis (NONMEM) of the concentration-effect relationship of levodopa according to a sigmoidal Emax model and over all dosage intervals did not show differences in levodopa responsiveness with or without tolcapone. The population mean of the 50% effective concentration (EC50) of levodopa was 1350 microg/L with an standard error of the population parameter estimate of 18%: adding tolcapone treatment as a covariate did not significantly change the population fit. Circadian influences on levodopa respon- siveness were not evaluable by the NONMEM model due to overparametrisation, but visual inspection of plotted data did not suggest differences in the concentration-effect relationship between the 4 consecutive dosage intervals on days 1 and 8. CONCLUSIONS: The gain in clinical improvement with levodopa under tolcapone can be fully explained by tolcapone-induced changes of peripheral levodopa pharmacokinetics. We suggest that this interaction study, performed in patients and using clinical data, excludes any central effects of tolcapone or any inhibiting effect of 3-OMD on levodopa permeation through the blood-brain barrier, which otherwise would have led to a decrease in the EC50 of levodopa.