Meditative scuba diving improved overall PTSD symptoms after one month more than multisport activity but not significantly.
PTSD Intrusion symptoms were significantly improved after one month by the ...meditative diving.
The positive effects of meditative diving faded after 3 months.
Post-Traumatic Stress Disorder (PTSD) is a chronic and disabling disease that currently has no fully effective therapeutic solution. Complementary approaches, such as relaxation, sport, or meditation, could be therapeutic aids for symptom reduction. Scuba diving combines sport and mindfulness training and has been found to have a positive effect on chronic stress and PTSD.
The first objective of this pilot study is to compare the effectiveness of diving associated with mindfulness exercises (the Bathysmed® protocol) with multisport activity in reducing PTSD symptoms. The secondary objective is to compare the impact of the Bathysmed® protocol on mindfulness functioning in the two groups of subjects suffering from PTSD.
This proof-of-concept took the form of a controlled randomized clinical trial. The primary endpoint was the severity of PTSD symptoms, measured by the PCL-5 (PTSD Check List) scale. Half of the group were exposed to the Bathysmed® protocol (the experimental condition), and the other half to a non-specific multisport program.
Bathysmed® protocol improved PCL-5 scores more than the multisport program but the result was not significant. The protocol was significantly better than the multisport activity in reducing intrusion symptoms of PTSD after one month. Globally, trait mindfulness scores improved up to one month after the course, but the result was not significant. Three months after the course, there was no difference between the two groups with regard to PCL-5 and Freiburg Mindfulness Inventory scores..
Our study demonstrates the value of the Bathysmed® protocol even though it suffers from a lack of power and could only obtain partial but encouraging results. Mindfulness must be practiced over the long term to achieve stable benefits. This probably explains why no differences persisted three months after the course. Further work is needed to confirm the initial results obtained with this pilot study.
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Within the components of Scuba diving there are similarities with meditation and mindfulness techniques by training divers to be in a state of open monitoring associated with slow and ample ...breathing. Perceived stress is known to be diminished during meditation practice. This study evaluates the benefits of scuba diving on perceived stress and mindful functioning.
A recreational diving group (RDG;
= 37) was compared with a multisport control group (MCG;
= 30) on perceived stress, mood, well-being and mindfulness by answering auto-questionnaires before and after a 1-week long UCPA course. For the diving group, stability of the effects was evaluated 1 month later using similar auto-questionnaires.
Perceived stress did not decrease after the course for the MCG The divers showed a significant reduction on the perceived stress score (
< 0.05) with a sustainable effect (
= 0.01). An improvement in mood scale was observed in both groups. This was associated to an increase in mindfulness abilities.
The practice of a recreational sport improves the mood of subjects reporting the thymic benefits of a physical activity performed during a vacation period. The health benefits of recreational diving appear to be greater than the practice of other sports in reducing stress and improving well-being.
Immersion pulmonary edema (IPE) is a misdiagnosed environmental illness caused by water immersion, cold, and exertion. IPE occurs typically during SCUBA diving, snorkeling, and swimming. IPE is ...sometimes associated with myocardial injury and/or loss of consciousness in water, which may be fatal. IPE is thought to involve hemodynamic and cardiovascular disturbances, but its pathophysiology remains largely unclear, which makes IPE prevention difficult. This observational study aimed to document IPE pathogenesis and improve diagnostic reliability, including distinguishing in some conditions IPE from decompression sickness (DCS), another diving-related disorder.Thirty-one patients (19 IPE, 12 DCS) treated at the Hyperbaric Medicine Department (Ste-Anne hospital, Toulon, France; July 2013-June 2014) were recruited into the study. Ten healthy divers were recruited as controls. We tested: (i) copeptin, a surrogate marker for antidiuretic hormone and a stress marker; (ii) ischemia-modified albumin, an ischemia/hypoxia marker; (iii) brain-natriuretic peptide (BNP), a marker of heart failure, and (iv) ultrasensitive-cardiac troponin-I (cTnI), a marker of myocardial ischemia.We found that copeptin and cardiac biomarkers were higher in IPE versus DCS and controls: (i) copeptin: 68% of IPE patients had a high level versus 25% of DCS patients (P < 0.05) (mean ± standard-deviation: IPE: 53 ± 61 pmol/L; DCS: 15 ± 17; controls: 6 ± 3; IPE versus DCS or controls: P < 0.05); (ii) ischemia-modified albumin: 68% of IPE patients had a high level versus 16% of DCS patients (P < 0.05) (IPE: 123 ± 25 arbitrary-units; DCS: 84 ± 25; controls: 94 ± 7; IPE versus DCS or controls: P < 0.05); (iii) BNP: 53% of IPE patients had a high level, DCS patients having normal values (P < 0.05) (IPE: 383 ± 394 ng/L; DCS: 37 ± 28; controls: 19 ± 15; IPE versus DCS or controls: P < 0.01); (iv) cTnI: 63% of IPE patients had a high level, DCS patients having normal values (P < 0.05) (IPE: 0.66 ± 1.50 μg/L; DCS: 0.0061 ± 0.0040; controls: 0.0090 ± 0.01; IPE versus DCS or controls: P < 0.01). The combined "BNP-cTnI" levels provided most discrimination: all IPE patients, but none of the DCS patients, had elevated levels of either/both of these markers.We propose that antidiuretic hormone acts together with a myocardial ischemic process to promote IPE. Thus, monitoring of antidiuretic hormone and cardiac biomarkers can help to make a quick and reliable diagnosis of IPE.
The peroxisome proliferator activated receptors PPARα, PPARγ, and PPARδ are ligand-activated transcription factors that play a key role in lipid homeostasis. The fibrates raise circulating levels of ...high-density lipoprotein cholesterol and lower levels of triglycerides in part through their activity as PPARα agonists; however, the low potency and restricted selectivity of the fibrates may limit their efficacy, and it would be desirable to develop more potent and selective PPARα agonists. Modification of the selective PPARδ agonist 1 (GW501516) so as to incorporate the 2-aryl-2-methylpropionic acid group of the fibrates led to a marked shift in potency and selectivity toward PPARα agonism. Optimization of the series gave 25a, which shows EC50 = 4 nM on PPARα and at least 500-fold selectivity versus PPARδ and PPARγ. Compound 25a (GW590735) has been progressed to clinical trials for the treatment of diseases of lipid imbalance.
IMPORTANCE: Rituximab and short-term corticosteroid therapy are the criterion standard treatments for patients with newly diagnosed moderate to severe pemphigus. OBJECTIVE: To examine factors ...associated with short-term relapse in patients with pemphigus treated with rituximab. DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis of a randomized clinical trial (Comparison Between Rituximab Treatment and Oral Corticosteroid Treatment in Patients With Pemphigus RITUX 3) conducted from January 1, 2010, to December 31, 2015, included patients from 20 dermatology departments of tertiary care centers in France from the RITUX 3 trial and 3 newly diagnosed patients treated according to the trial protocol. Data analysis was performed from February 1 to June 30, 2019. EXPOSURE: Patients randomly assigned to the rituximab group in the RITUX 3 trial and the 3 additional patients were treated with 1000 mg of intravenous rituximab on days 0 and 14 and 500 mg at months 12 and 18 combined with a short-term prednisone regimen. MAIN OUTCOMES AND MEASURES: Baseline (pretreatment) clinical and biological characteristics (Pemphigus Disease Area Index PDAI score, ranging from 0-250 points, with higher values indicating more severe disease) and changes in anti–desmoglein (DSG) 1 and anti-DSG3 values as measured by enzyme-linked immunosorbent assay during the 3 months after rituximab treatment were compared between patients with disease relapse and those who maintained clinical remission during the first 12 months after treatment. The positive and negative predictive values of these factors were calculated. RESULTS: Among 47 patients (mean SD age, 54.3 17.0 years; 17 36% male and 30 64% female) included in the study, the mean (SD) baseline PDAI score for patients with relapsing disease was higher than that of the patients with nonrelapsing disease (54 33 vs 28 24; P = .03). At month 3, 7 of 11 patients with relapsing disease (64%) vs 7 of 36 patients with nonrelapsing disease (19%) had persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher (P = .01). A PDAI score of 45 or higher defining severe pemphigus and/or persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher at month 3 provided a positive predictive value of 50% (95% CI, 27%-73%) and a negative predictive value of 94% (95% CI, 73%-100%) for the occurrence of relapse after rituximab. CONCLUSIONS AND RELEVANCE: The findings suggest that initial PDAI score and changes in anti-DSG antibody values after the initial cycle of rituximab might help differentiate a subgroup of patients with high risk of relapse who might benefit from maintenance rituximab infusion at month 6 from a subgroup of patients with low risk of relapse who do not need early maintenance therapy. TRIAL REGISTRATION: NCT00784589
IMPORTANCE: The Ritux 3 trial demonstrated the short-term efficacy and safety of first-line treatment with rituximab compared with a standard corticosteroid regimen in pemphigus. No data on the ...long-term follow-up of patients who received rituximab as first line are available. OBJECTIVE: To assess the long-term efficacy and safety of the Ritux 3 treatment regimen. DESIGN, SETTING, AND PARTICIPANTS: This 7-year follow-up study of the Ritux 3 trial included patients with pemphigus from 25 dermatology departments in France from January 1, 2010, to December 31, 2015. EXPOSURE: Patients were initially randomized in the rituximab plus prednisone group or prednisone-alone group. MAIN OUTCOMES AND MEASURES: The primary outcome was the 5- and 7-year disease-free survival (DFS) without corticosteroids, assessed by Kaplan-Meier curves. Secondary outcomes were occurrence of relapse, occurrence of severe adverse events (SAEs), and evolution of antidesmoglein (Dsg) antibody enzyme-linked immunosorbent assay values to predict long-term relapse. RESULTS: Of the 90 patients in the Ritux 3 trial, 83 were evaluated at the end of follow-up study visit (44 in the rituximab plus prednisone group; 39 in the prednisone-alone group) with a median (IQR) follow-up of 87.3 (79.1-97.5) months. Forty-three patients (93%) from the rituximab plus prednisone and 17 patients (39%) from the prednisone-alone group had achieved complete remission without corticosteroids at any time during the follow-up. Patients from the rituximab group had much longer 5- and 7-year DFS without corticosteroids than patients from the prednisone-alone group (76.7% and 72.1% vs 35.3% and 35.3%, respectively; P < .001), and had about half the relapses (42.2% vs 83.7%; P < .001). Patients who received rituximab as second-line treatment had shorter DFS than patients treated as first line (P = .007). Fewer SAEs were reported in the rituximab plus prednisone group compared with the prednisone-alone group, 31 vs 58 respectively, corresponding to 0.67 and 1.32 SAEs per patient, respectively (P = .003). The combination of anti-Dsg1 values of 20 or more IU/mL and/or anti-Dsg3 values of 48 or more IU/mL yielded 0.83 positive predictive value and 0.94 negative predictive value to predict long-term relapse. CONCLUSIONS AND RELEVANCE: In this secondary analysis of the Ritux 3 trail, first-line treatment of patients with pemphigus with the Ritux 3 regimen was associated with long-term sustained complete remission without corticosteroid therapy without any additional maintenance infusion of rituximab.
Objective
To determine whether a single session of botulinum toxin type A (BTA) injections into both hands more effectively decreases the frequency of systemic sclerosis–associated Raynaud's ...phenomenon (SSc‐RP) episodes than placebo.
Methods
This multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group phase III trial in patients with SSc‐RP assessed the effect of 50‐unit BTA or placebo injections into the palms of both hands around each neurovascular bundle during 1 session in winter. The primary end point was the between‐group difference in the median change in the number of RP episodes from baseline (day 0) to 4 weeks postinjection. Values between the groups were compared with the Wilcoxon rank‐sum test.
Results
The intent‐to‐treat analysis included 46 BTA‐treated patients and 44 placebo recipients. At 4 weeks after assigned treatment injections, the median number of daily RP episodes decreased comparably in the BTA and placebo groups (median change –1 episode/day interquartile range (IQR) –1.5, 0 episodes/day and –1 episode/day IQR –2.5, 0 episodes/day, respectively) (P = 0.77 versus placebo). Moreover, change in Raynaud's Condition Score, quality of life assessed by Health Assessment Questionnaire disability index, and hand function assessed by shortened Disabilities of the Arm, Shoulder, and Hand (QuickDASH) and Cochin Hand Function Scale from baseline to follow‐up weeks 4, 12, and 24 did not differ significantly between groups. The BTA group experienced transient hand muscle weakness significantly more frequently (P = 0.003).
Conclusion
Neither the primary nor secondary end points were reached, and our results do not support any beneficial effect of palmar BTA injections to treat SSc‐RP.
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Summary Background High doses of corticosteroids are considered the standard treatment for pemphigus. Because long-term corticosteroid treatment can cause severe and even life-threatening ...side-effects in patients with this disease, we assessed whether first-line use of rituximab as adjuvant therapy could improve the proportion of patients achieving complete remission off-therapy, compared with corticosteroid treatment alone, while decreasing treatment side-effects of corticosteroids. Methods We did a prospective, multicentre, parallel-group, open-label, randomised trial in 25 dermatology hospital departments in France (Ritux 3). Eligible participants were patients with newly diagnosed pemphigus aged 18–80 years being treated for the first time (not at the time of a relapse). We randomly assigned participants (1:1) to receive either oral prednisone alone, 1·0 or 1·5 mg/kg per day tapered over 12 or 18 months (prednisone alone group), or 1000 mg of intravenous rituximab on days 0 and 14, and 500 mg at months 12 and 18, combined with a short-term prednisone regimen, 0·5 or 1·0 mg/kg per day tapered over 3 or 6 months (rituximab plus short-term prednisone group). Follow-up was for 3 years (study visits were scheduled weekly during the first month of the study, then monthly until month 24, then an additional visit at month 36). Treatment was assigned through central computer-generated randomisation, with stratification according to disease-severity (severe or moderate, based on Harman's criteria). The primary endpoint was the proportion of patients who achieved complete remission off-therapy at month 24 (intention-to-treat analysis). This study is registered with ClinicalTrials.gov , number NCT00784589. Findings Between May 10, 2010, and Dec 7, 2012, we enrolled 91 patients and randomly assigned 90 to treatment (90 were analysed; 1 patient withdrew consent before the random assignment). At month 24, 41 (89%) of 46 patients assigned to rituximab plus short-term prednisone were in complete remission off-therapy versus 15 (34%) of 44 assigned to prednisone alone (absolute difference 55 percentage points, 95% CI 38·4–71·7; p<0·0001. This difference corresponded to a relative risk of success of 2·61 (95% CI 1·71–3·99, p<0·0001), corresponding to 1·82 patients (95% CI 1·39–2·60) who would need to be treated with rituximab plus prednisone (rather than prednisone alone) for one additional success. No patient died during the study. More severe adverse events of grade 3–4 were reported in the prednisone-alone group (53 events in 29 patients; mean 1·20 SD 1·25) than in the rituximab plus prednisone group (27 events in 16 patients; mean 0·59 1·15; p=0·0021). The most common of these events in both groups were diabetes and endocrine disorder (11 21% with prednisone alone vs six 22% with rituximab plus prednisone), myopathy (ten 19% vs three 11%), and bone disorders (five 9% vs five 19%). Interpretation Data from our trial suggest that first-line use of rituximab plus short-term prednisone for patients with pemphigus is more effective than using prednisone alone, with fewer adverse events. Funding French Ministry of Health, French Society of Dermatology, Roche.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Introduction
Therapeutic drug monitoring of mycophenolate mofetil is recommended because of the interindividual variability in the exposition to its active moiety, mycophenolic acid. However, most of ...the pharmacokinetic studies involved patients cotreated with cyclosporine (INN, ciclosporin).
Methods
We analyzed the pharmacokinetics of mycophenolic acid in 13 renal graft recipients treated with sirolimus in an anticalcineurin–free regimen and compared it with that of 17 patients cotreated with cyclosporine. The area under the concentration versus time curve over a 12–hour period (AUC0–12) of mycophenolic acid was estimated at 2 weeks, 1 month, 2 months, and 3 months after transplantation.
Results
At the first 3 time points, patients cotreated with sirolimus had significantly higher mycophenolic acid AUC0–12 values compared with patients cotreated with cyclosporine, as follows: 81 mg · h/L (SD, 39 mg · h/L) versus 43 mg · h/L (SD, 11 mg · h/L) (P < .001), 72 mg · h/L (SD, 17 mg · h/L) versus 48 mg · h/L (SD, 13 mg · h/L) (P < .001), and 70 mg · h/L (SD, 25 mg · h/L) versus 47 mg · h/L (SD, 17 mg · h/L) (P < .01) at week 2, month 1, and month 2, respectively. At all time points, patients cotreated with sirolimus had significantly higher dose–normalized mycophenolic acid AUC0–12 values. At months 1 and 2, white blood cell counts were lower in the sirolimus group than in the cyclosporine group, as follows: 4.8×103/mL (SD, 1.1×103/mL) versus 6.5×103/mL (SD, 2.2×103/mL) (P < .01) at month 1 and 4.6×103/mL (SD, 1.1×103/mL) versus 5.9×103/mL (SD, 2.0×103/mL) (P < .05) at month 2.
Conclusion
These data show that exposure to mycophenolic acid is higher in patients cotreated with sirolimus than in those cotreated with cyclosporine.
Clinical Pharmacology & Therapeutics (2005) 78, 34–42; doi: 10.1016/j.clpt.2005.03.005
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