Biomedical Research Institute Sant Pau

Barcelona, Spain

Biomedical Research Institute Sant Pau

Barcelona, Spain

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Hervera A.,Biomedical Research Institute Sant Pau | Leanez S.,Biomedical Research Institute Sant Pau | Motterlini R.,University Paris Est Creteil | Pol O.,Biomedical Research Institute Sant Pau
Anesthesiology | Year: 2013

Background: The administration of μ-opioid receptors (MOR) and δ-opioid receptors (DOR) as well as cannabinoid-2 receptor (CB2R) agonists attenuates neuropathic pain. We investigated if treatment with two carbon monoxide-releasing molecules (CORM-2 and CORM-3) or an inducible heme oxygenase inducer (cobalt protoporphyrin IX, CoPP) could modulate the local and systemic effects and expression of MOR, DOR, and CB2R during neuropathic pain. Methods: In C57BL/6 mice, at 10 days after the chronic constriction of sciatic nerve, we evaluated the effects of the intraperitoneal administration of 10 mg/kg of CORM-2, CORM-3, or CoPP on the antiallodynic and antihyperalgesic actions of a locally or systemically administered MOR (morphine), DOR ([d-Pen(2),d-Pen(5)]- enkephalin) or CB2R ((2-methyl-1-propyl-1H-indol-3-yl)-1-naphthalenylmethanone ) agonist. The effects of CORM-2 and CoPP treatments on the expression of MOR, DOR, CB2R, inducible and constitutive heme oxygenases, microglia activation marker (CD11b/c), and neuronal and inducible nitric oxide synthases were also assessed. Results: Treatments with CO-RMs and CoPP reduced the mechanical and thermal hypersensitivity induced by sciatic nerve injury, increased the local, but not systemic, antinociceptive effects of morphine, and decreased those produced by DPDPE and JWH-015. Both CORM-2 and CoPP treatments enhanced MOR and inducible heme oxygenase expression, unaltered DOR and constitutive heme oxygenase expression, and decreased the overexpression of CB2R, CD11b/c, and neuronal and inducible nitric oxide synthases induced by sciatic nerve injury. Conclusions: This study shows that CO-RMs and CoPP treatments increase the local antinociceptive effects of morphine through enhancing MOR peripheral expression and inhibiting spinal microglial activation and overexpression of neuronal/inducible nitric oxide synthases. © 2013 the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.


Alonso-Coello P.,Biomedical Research Institute Sant Pau | Zhou Q.,McMaster University | Guyatt G.,McMaster University
Thrombosis and Haemostasis | Year: 2012

Oral anticoagulation with vitamin k antagonists (VKAs) requires regular testing and dose adjustment. Home-monitoring (self-testing or self-management) is more effective than usual management. Dabigatran, does not require dose-adjustment and appears to be more effective at reducing the risk of stroke with similar risks of bleeding in patients with atrial fibrillation (AF). Dabigatran, however, has not been compared to the homemonitoring. It was the objective to evaluate the efficacy of dabigatran compared with home-monitoring of oral anticoagulation with VKAs. Randomised controlled trials (RCTs) comparing usual management of oral anticoagulation with home-monitoring, dabigatran with usual management, and RCTs comparing dabigatran with home-monitoring and including patient-important outcomes (thromboembolic events, death and major bleeding) were eligible. For our direct comparison we calculated pooled relative risks (RRs) using the Mantzel-Haenzel random effect model. For the indirect comparison we estimated lnRRs and back transformed to RR. We evaluated the quality of the evidence with the GRADE system. Dabigatran, compared with warfarin, was associated with lower rates of stroke or thromboembolism and systemic embolism but similar rates of major haemorrhage and death. Dabigatran 150 mg also increased non-significantly the rate of myocardial infarction. The quality of the evidence was high. Our indirect comparison of home-monitoring of oral anticoagulation versus dabigatran showed no convincing differences in the risk of thromboembolism, death or major bleeding. The estimates for selfmanagement vs. dabigatran showed stronger but still non-significant trends. The quality of the evidence was low. In conclusion, the indirect comparison of home monitoring of oral anticoagulation with dabigatran suggests that the treatments have similar impact on thrombosis, bleeding and death. However, the confidence in the estimate of effect is low to very low. Our analyses contrast with the available comparison of dabigatran with conventional warfarin monitoring. © Schattauer 2012.


Barajas-Nava L.A.,Biomedical Research Institute Sant Pau
The Cochrane database of systematic reviews | Year: 2013

Infection of burn wounds is a serious problem because it can delay healing, increase scarring and invasive infection may result in the death of the patient. Antibiotic prophylaxis is one of several interventions that may prevent burn wound infection and protect the burned patient from invasive infections. To assess the effects of antibiotic prophylaxis on rates of burn wound infection. In January 2013 we searched the Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid MEDLINE - In-Process & Other Non-Indexed Citations (2013); Ovid EMBASE; EBSCO CINAHL and reference lists of relevant articles. There were no restrictions with respect to language, date of publication or study setting. All randomised controlled trials (RCTs) that evaluated the efficacy and safety of antibiotic prophylaxis for the prevention of BWI. Quasi-randomised studies were excluded. Two review authors independently selected studies, assessed the risk of bias, and extracted relevant data. Risk ratio (RR) and mean difference (MD) were estimated for dichotomous data and continuous data, respectively. When sufficient numbers of comparable RCTs were available, trials were pooled in a meta-analysis to estimate the combined effect. This review includes 36 RCTs (2117 participants); twenty six (72%) evaluated topical antibiotics, seven evaluated systemic antibiotics (four of these administered the antibiotic perioperatively and three administered upon hospital admission or during routine treatment), two evaluated prophylaxis with non absorbable antibiotics, and one evaluated local antibiotics administered via the airway.The 11 trials (645 participants) that evaluated topical prophylaxis with silver sulfadiazine were pooled in a meta analysis. There was a statistically significant increase in burn wound infection associated with silver sulfadiazine compared with dressings/skin substitute (OR = 1.87; 95% CI: 1.09 to 3.19, I(2) = 0%). These trials were at high, or unclear, risk of bias. Silver sulfadiazine was also associated with significantly longer length of hospital stay compared with dressings/skin substitute (MD = 2.11 days; 95% CI: 1.93 to 2.28).Systemic antibiotic prophylaxis in non-surgical patients was evaluated in three trials (119 participants) and there was no evidence of an effect on rates of burn wound infection. Systemic antibiotics (trimethoprim-sulfamethoxazole) were associated with a significant reduction in pneumonia (only one trial, 40 participants) (RR = 0.18; 95% CI: 0.05 to 0.72) but not sepsis (two trials 59 participants) (RR = 0.43; 95% CI: 0.12 to 1.61).Perioperative systemic antibiotic prophylaxis had no effect on any of the outcomes of this review.Selective decontamination of the digestive tract with non-absorbable antibiotics had no significant effect on rates of all types of infection (2 trials, 140 participants). Moreover, there was a statistically significant increase in rates of MRSA associated with use of non-absorbable antibiotics plus cefotaxime compared with placebo (RR = 2.22; 95% CI: 1.21 to 4.07).There was no evidence of a difference in mortality or rates of sepsis with local airway antibiotic prophylaxis compared with placebo (only one trial, 30 participants). The conclusions we are able to draw regarding the effects of prophylactic antibiotics in people with burns are limited by the volume and quality of the existing research (largely small numbers of small studies at unclear or high risk of bias for each comparison). The largest volume of evidence suggests that topical silver sulfadiazine is associated with a significant increase in rates of burn wound infection and increased length of hospital stay compared with dressings or skin substitutes; this evidence is at unclear or high risk of bias. Currently the effects of other forms of antibiotic prophylaxis on burn wound infection are unclear. One small study reported a reduction in incidence of pneumonia associated with a specific systematic antibiotic regimen.


Clinicians, providers and guideline panels use absolute effects to weigh the advantages and downsides of treatment alternatives. Relative measures have the potential to mislead readers. However, little is known about the reporting of absolute measures in systematic reviews. The objectives of our study are to determine the proportion of systematic reviews that report absolute measures of effect for the most important outcomes, and ascertain how they are analyzed, reported and interpreted. We will conduct a methodological survey of systematic reviews published in 2010. We will conduct a 1:1 stratified random sampling of Cochrane vs. non-Cochrane systematic reviews. We will calculate the proportion of systematic reviews reporting at least one absolute estimate of effect for the most patient-important outcome for the comparison of interest. We will conduct multivariable logistic regression analyses with the reporting of an absolute estimate of effect as the dependent variable and pre-specified study characteristics as the independent variables. For systematic reviews reporting an absolute estimate of effect, we will document the methods used for the analysis, reporting and interpretation of the absolute estimate. Our methodological survey will inform current practices regarding reporting of absolute estimates in systematic reviews. Our findings may influence recommendations on reporting, conduct and interpretation of absolute estimates. Our results are likely to be of interest to systematic review authors, funding agencies, clinicians, guideline developers and journal editors.


Tort S.,Biomedical Research Institute Sant Pau
Cochrane database of systematic reviews (Online) | Year: 2012

Fibromyalgia (FM) syndrome is a chronic condition of unknown aetiology characterised by musculoskeletal pain that often co-exists with sleep disturbance, cognitive dysfunction and fatigue. Patients often report high disability levels and poor quality of life. Since there is no specific treatment that alters the pathogenesis of FM, drug therapy focuses on pain reduction and improvement of other bothersome symptoms. The objective of this review was to assess the effectiveness and safety of monoamine oxidase inhibitors (MAOIs) in the treatment of FM syndrome. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 10), MEDLINE (1966 to November 2010), EMBASE (1980 to November 2010) and the reference lists of reviewed articles. We selected all randomised, double-blind trials of MAOIs used for the treatment of FM pain in adult participants. Two authors assessed risk of bias and extracted data independently onto a specially designed pro forma and a third review author cross-checked them. We included two studies of inconsistent risk of bias with a total of 230 patients diagnosed with FM. We evaluated two MAOIs: pirlindole and moclobemide. Pirlindole showed statistically significant results compared with placebo for several outcomes (pain, tender points and overall assessment by the patient and the physician), whereas moclobemide did not show statistically significant differences between groups. Pooled results of the two studies displayed a modest effect size in pain (mean difference (MD) -1.45 (121 patients; 95% confidence interval (CI) -2.71 to -0.20; number needed to treat (NNT) 2 (95% CI 1 to 12); I(2) = 59%)), implying a minimal clinically important difference (MCID) and a small effect on tender points (standardised mean difference (SMD) -0.36 (121 patients; 95% CI -0.72 to -0.00; I(2) = 31%)). No effect was seen on global assessment by patient. Physical function and sleep disturbance were not measured. The most frequent adverse events were nausea and vomiting, with statistically significant differences between groups (risk ratio (RR) 7.82 (89 patients; 95% CI 1.02 to 59.97; NNT 7 (95% CI 4 to 33)). Data suggest that the effectiveness of MAOIs for the treatment of FM symptoms is limited. Although we observed a moderate effect size on pain and a small one on tender points, these results should be taken with caution as they are only based on two studies with a small number of patients and inconsistent risk of bias among them.


Roque i Figuls M.,Biomedical Research Institute Sant Pau | Roque i Figuls M.,Autonomous University of Barcelona
Cochrane database of systematic reviews (Online) | Year: 2012

This is an update of the original Cochrane review published in 2005 and updated in 2007. Acute bronchiolitis is the leading cause of medical emergencies during winter in children younger than two years of age. Chest physiotherapy is thought to assist infants in the clearance of secretions and to decrease ventilatory effort. The main objective was to determine the efficacy of chest physiotherapy in infants aged less than 24 months old with acute bronchiolitis. A secondary objective was to determine the efficacy of different techniques of chest physiotherapy (for example, vibration and percussion and passive forced exhalation). We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4) which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to November week 3, 2011), MEDLINE in-process and other non-indexed citations (8 December 2011), EMBASE.com (1990 to December 2011), CINAHL (1982 to December 2011), LILACS (1985 to December 2011) and Web of Science (1985 to December 2011). Randomised controlled trials (RCTs) in which chest physiotherapy was compared against no intervention or against another type of physiotherapy in bronchiolitis patients younger than 24 months of age. Two review authors independently extracted data. Primary outcomes were respiratory parameters and improvement in severity of disease. Secondary outcomes were length of hospital stay, duration of oxygen supplementation and the use of bronchodilators and steroids. No pooling of data was possible. Nine clinical trials including 891 participants were included comparing physiotherapy with no intervention. Five trials (246 participants) evaluated vibration and percussion techniques and four trials (645 participants) evaluated passive expiratory techniques. We observed no significant differences in the severity of disease (eight trials, 867 participants). Results were negative for both types of physiotherapy. We observed no differences between groups in respiratory parameters (two trials, 118 participants), oxygen requirements (one trial, 50 participants), length of stay (five trials, 222 participants) or severe side effects (two trials, 595 participants). Differences in mild transient adverse effects (vomiting and respiratory instability) have been observed (one trial, 496 participants). Since the last publication of this review new good-quality evidence has appeared, strengthening the conclusions of the review. Chest physiotherapy does not improve the severity of the disease, respiratory parameters, or reduce length of hospital stay or oxygen requirements in hospitalised infants with acute bronchiolitis not on mechanical ventilation. Chest physiotherapy modalities (vibration and percussion or forced expiratory techniques) have shown equally negative results.


Martinez Garcia L.,Biomedical Research Institute Sant Pau
Implementation science : IS | Year: 2012

Scientific knowledge is in constant change. The flow of new information requires a frequent re-evaluation of the available research results. Clinical practice guidelines (CPGs) are not exempted from this phenomenon and need to be kept updated to maintain the validity of their recommendations. The objective of our review is to systematically identify, describe and assess strategies for monitoring and updating CPGs. We conducted a systematic review of studies evaluating one or more methods of updating (with or without monitoring) CPGs or recommendations. We searched MEDLINE (PubMed) and The Cochrane Methodology Register (The Cochrane Library) from 1966 to June 2012. Additionally, we hand-searched reference lists of the included studies and the Guidelines International Network book of abstracts. If necessary, we contacted study authors to obtain additional information. We included a total of eight studies. Four evaluated if CPGs were out of date, three updated CPGs, and one continuously monitored and updated CPGs. The most detailed reported phase of the process was the identification of new evidence. As opposed to studies updating guidelines, studies evaluating if CPGs were out of date applied restricted searches. Only one study compared a restricted versus an exhaustive search suggesting that a restricted search is sufficient to assess recommendations' Validity. One study analyzed the survival time of CPGs and suggested that these should be reassessed every three years. There is limited evidence about the optimal strategies for monitoring and updating clinical practice guidelines. A restricted search is likely to be sufficient to monitor new evidence and assess the need to update, however, more information is needed about the timing and type of search. Only the exhaustive search strategy has been assessed for the update of CPGs. The development and evaluation of more efficient strategies is needed to improve the timeliness and reduce the burden of maintaining the validity of CPGs.


Riba J.,Biomedical Research Institute Sant Pau
Drug testing and analysis | Year: 2012

Ayahuasca is an Amazonian psychotropic plant tea obtained from Banisteriopsis caapi, which contains β-carboline alkaloids, chiefly harmine, harmaline and tetrahydroharmine. The tea usually incorporates the leaves of Psychotria viridis or Diplopterys cabrerana, which are rich in N,N-dimethyltryptamine (DMT), a psychedelic 5-HT(2A/1A/2C) agonist. The β-carbolines reversibly inhibit monoamine-oxidase (MAO), effectively preventing oxidative deamination of the orally labile DMT and allowing its absorption and access to the central nervous system. Despite increased use of the tea worldwide, the metabolism and excretion of DMT and the β-carbolines has not been studied systematically in humans following ingestion of ayahuasca. In the present work, we used an analytical method involving high performance liquid chromatography (HPLC)/electrospray ionization (ESI)/selected reaction monitoring (SRM)/tandem mass spectrometry(MS/MS) to characterize the metabolism and disposition of ayahuasca alkaloids in humans. Twenty-four-hour urine samples were obtained from 10 healthy male volunteers following administration of an oral dose of encapsulated freeze-dried ayahuasca (1.0 mg DMT/kg body weight). Results showed that less than 1% of the administered DMT dose was excreted unchanged. Around 50% was recovered as indole-3-acetic acid but also as DMT-N-oxide (10%) and other MAO-independent compounds. Recovery of DMT plus metabolites reached 68%. Harmol, harmalol, and tetrahydroharmol conjugates were abundant in urine. However, recoveries of each harmala alkaloid plus its O-demethylated metabolite varied greatly between 9 and 65%. The present results show the existence in humans of alternative metabolic routes for DMT other than biotransformation by MAO. Also that O-demethylation plus conjugation is an important but probably not the only metabolic route for the harmala alkaloids in humans. Copyright © 2012 John Wiley & Sons, Ltd.


Roque I Figuls M.,Biomedical Research Institute Sant Pau
Cochrane database of systematic reviews (Online) | Year: 2011

This is an update of the review published in Issue 4, 2003. Bone metastasis cause severe pain as well as pathological fractures, hypercalcaemia and spinal cord compression. Treatment strategies currently available to relieve pain from bone metastases include analgesia, radiotherapy, surgery, chemotherapy, hormone therapy, radioisotopes and bisphosphonates. To determine efficacy and safety of radioisotopes in patients with bone metastases to improve metastatic pain, decrease number of complications due to bone metastases and improve patient survival. We sought randomised controlled trials (RCTs) in MEDLINE, EMBASE, CENTRAL, and the PaPaS Trials Register up to October 2010. Studies selected had metastatic bone pain as a major outcome after treatment with a radioisotope, compared with placebo or another radioisotope. We assessed the risk of bias of included studies by their sequence generation, allocation concealment, blinding of study participants, researchers and outcome assessors, and incomplete outcome data. Two review authors extracted data. We performed statistical analysis as an "available case" analysis, and calculated global estimates of effect using a random-effects model. We also performed an intention-to-treat (ITT) sensitivity analysis. This update includes 15 studies (1146 analyzed participants): four (325 participants) already included and 11 new (821 participants). Only three studies had a low risk of bias. We observed a small benefit of radioisotopes for complete relief (risk ratio (RR) 2.10, 95% CI 1.32 to 3.35; Number needed to treat to benefit (NNT) = 5) and complete/partial relief (RR 1.72, 95% CI 1.13 to 2.63; NNT = 4) in the short and medium term (eight studies, 499 participants). There is no conclusive evidence to demonstrate that radioisotopes modify the use of analgesia with respect to placebo. Leucocytopenia and thrombocytopenia are secondary effects significantly associated with the administration of radioisotopes (RR 5.03; 95% CI 1.35 to 18.70; Number needed to treat to harm (NNH) = 13). Pain flares were not higher in the radioisotopes group (RR 0.74; 95% CI 0.27 to 2.06). There are scarce data of moderate quality when comparing Strontium-89 ((89)Sr) with Samarium-153 ((153)Sm), Rhenium-186 ((186)Re) and Phosphorus-32 ((32)P). We observed no significant differences between treatments. Similarly, we observed no differences when we compared different doses of (153)Sm (0.5 versus 1.0 mCi). This update adds new evidence on efficacy of radioisotopes versus placebo, (89)Sr compared with other radioisotopes, and dose-comparisons of (153)Sm and (188)Re. There is some evidence indicating that radioisotopes may provide complete reduction in pain over one to six months with no increase in analgesic use, but severe adverse effects (leucocytopenia and thrombocytopenia) are frequent.


Torrego A.,Biomedical Research Institute Sant Pau
The Cochrane database of systematic reviews | Year: 2014

Bronchial thermoplasty is a procedure that consists of the delivery of controlled radiofrequency-generated heat via a catheter inserted into the bronchial tree of the lungs through a flexible bronchoscope. It has been suggested that bronchial thermoplasty works by reducing airway smooth muscle, thereby reducing the ability of the smooth muscle to bronchoconstrict. This treatment could then reduce asthma symptoms and exacerbations, resulting in improved asthma control and quality of life. To determine the efficacy and safety of bronchial thermoplasty in adults with bronchial asthma. We searched the Cochrane Airways Group Specialised Register of Trials (CAGR) up to January 2014. We included randomised controlled clinical trials that compared bronchial thermoplasty versus any active control in adults with moderate or severe persistent asthma. Our primary outcomes were quality of life, asthma exacerbations and adverse events. Two review authors independently extracted data and assessed risk of bias. We included three trials (429 participants) with differences regarding their design (two trials compared bronchial thermoplasty vs medical management and the other compared bronchial thermoplasty vs a sham intervention) and participant characteristics; one of the studies included participants with more symptomatic asthma compared with the others.The pooled analysis showed improvement in quality of life at 12 months in participants who received bronchial thermoplasty that did not reach the threshold for clinical significance (3 trials, 429 participants; mean difference (MD) in Asthma Quality of Life Questionnaire (AQLQ) scores 0.28, 95% confidence interval (CI) 0.07 to 0.50; moderate-quality evidence). Measures of symptom control showed no significant differences (3 trials, 429 participants; MD in Asthma Control Questionnaire (ACQ) scores -0.15, 95% CI -0.40 to 0.10; moderate-quality evidence). The risk of bias for these outcomes was high because two of the studies did not have a sham intervention for the control group.The results from two trials showed a lower rate of exacerbation after 12 months of treatment for participants who underwent bronchial thermoplasty. The trial with sham intervention showed a significant reduction in the proportion of participants visiting the emergency department for respiratory symptoms, from 15.3% on sham treatment to 8.4% over 12 months following thermoplasty. The trials showed no significant improvement in pulmonary function parameters (with the exception of a greater increase in morning peak expiratory flow (PEF) in one trial). Treated participants who underwent bronchial thermoplasty had a greater risk of hospitalisation for respiratory adverse events during the treatment period (3 trials, 429 participants; risk ratio 3.50, 95% CI 1.26 to 9.68; high-quality evidence), which represents an absolute increase from 2% to 8% (95% CI 3% to 23%) over the treatment period. This means that six of 100 participants treated with thermoplasty (95% CI 1 to 21) would require an additional hospitalisation over the treatment period. No significant difference in the risk of hospitalisation was noted at the end of the treatment period.Bronchial thermoplasty was associated with an increase in respiratory adverse events, mainly during the treatment period. Most of these events were mild or moderate, appeared in the 24-hour post-treatment period, and were resolved within a week. Bronchial thermoplasty for patients with moderate to severe asthma provides a modest clinical benefit in quality of life and lower rates of asthma exacerbation, but no significant difference in asthma control scores. The quality of life findings are at risk of bias, as the main benefits were seen in the two studies that did not include a sham treatment arm. This procedure increases the risk of adverse events during treatment but has a reasonable safety profile after completion of the bronchoscopies. The overall quality of evidence regarding this procedure is moderate. For clinical practice, it would be advisable to collect data from patients systematically in independent clinical registries. Further research should provide better understanding of the mechanisms of action of bronchial thermoplasty, as well as its effect in different asthma phenotypes or in patients with worse lung function.

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