Antoni Vallano

Inhaled antibiotic therapy in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa

The aim of this study was to investigate the long-term effectiveness and safety of inhaled antibiotic treatment in non-cystic fibrosis patients with bronchiectasis and chronic infection by Pseudomonas aeruginosa, after standard endovenous and oral therapy for long-term control of the infection had failed. After completing a 2-week endovenous antibiotic treatment to stabilize respiratory status, 17 patients were randomly allocated to a 12-month treatment either with inhaled ceftazidime and tobramycin (group A) or a symptomatic treatment (group B). One patient from group A abandoned inhaled treatment because of bronchospasm and another from group B died before the end of the study. The remaining 15 patients, seven from group A and eight from group B, completed the study. Both groups had similar previous characteristics. The number of admissions and days of admission (mean +/- SEM) of group A [0.6 (1.5) and 13.1 (34.8)] were lower than those of group B [2.5 (2.1) and 57.9 (41.8)] (P < 0.05). Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), PAO2 and PACO2 were similar in the two groups at the end of follow-up, showing a comparable decline in these parameters. There were no significant differences either in the use of oral antibiotics or in the frequency of emergence of antibiotic-resistant bacteria between groups. Microbiological studies suggested that several patients had different Pseudomonas aeruginosa strains. None of the patients presented impaired renal or auditory function at the end of the study. This study suggests that long-term inhaled antibiotic therapy may be safe and lessen disease severity in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa which do not respond satisfactorily to antibiotics administered via other routes.

A critical review of guidelines for low back pain treatment

Main problem: Little is known about the methodological quality of guidelines for low back pain treatment. We evaluated the methods used by the developers according to established standards. Methods: PubMed, guideline databases, and the World Wide Web were used to identify guidelines. Seventeen guidelines met the inclusion criteria: interventions for low back pain stated, recommendations based on or explicitly linked to evidence, and English version available. Guidelines were evaluated independently by two appraisers using a practical tool for this purpose, Users’ Guides to the Medical Literature, and the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument. Results: Thirteen guidelines (76%) specified the most important therapies applied, but only nine (53%) included a complete description of the target population. Explicit processes to identify, select, and combine evidence were described in only six guidelines (35%). Few guidelines (3; 18%) explicitly considered all main outcomes when formulating therapeutic recommendations, and none contained a process to determine the relative value of different outcomes. Methodological criteria for grading the strength of the recommendations varied, and were often insufficiently specified. None of the guidelines assessed the impact of uncertainty associated with the evidence and values used. According to AGREE the quality score was highest for the scope and purpose, and clarity and presentation domains, and lowest for editorial independence and applicability. With regard to the recommendations, there was consensus for some of the interventions for acute pain (analgesics and NSAIDs, maintaining physical activity, and avoiding excessive bed rest), but explicit recommendations were lacking or ambiguous for 41% of the interventions. Most of the guidelines did not contemplate specific recommendations for chronic pain. Conclusions: A small number of the available guidelines for low back pain treatment achieved acceptable results for specific quality criteria. In general, the methods to develop the guidelines’ therapeutic recommendations need to be more rigorous, more explicit and better explained. In addition, greater importance should be placed on the recommendations for chronic pain.

Oral antispastic drugs in nonprogressive neurologic diseases: A systematic review

Objective: To assess the efficacy of oral drugs in the treatment of spasticity in patients with nonprogressive neurologic disease (NPND). Methods: Systematic review of double-blind randomized controlled trials of antispastic oral drugs in the treatment of spasticity in NPND. Data sources: Electronic MEDLINE, PubMed, Cochrane Library, and hand searches. Results: Twelve studies (469 patients) were included (6 on stroke, 3 on spinal cord diseases, and 3 on cerebral palsy). Tizanidine was assessed in four trials (276 patients, 142 exposed), dantrolene in four (103, 93), baclofen in three (70, 55), diazepam in two (127, 76), and gabapentin in one (28, all exposed). Most trials were of small size, of short duration, and their methodologic quality was inadequate. Ten trials were controlled with placebo and only two were direct comparisons between drugs. Efficacy outcome variables were heterogeneous. Only four reports described the magnitude of the antispastic effect. The incidence of adverse drug effects (drowsiness, sedation, and muscle weakness) was high. Conclusion: Evidence on the efficacy of oral antispastic drugs in NPND is weak and does not include evaluation of patients’ quality of life. If any, efficacy is marginal. Adverse drug reactions were common. Better methodologic instruments are needed for the evaluation of antispastic treatment.

An Intervention to Improve Spontaneous Adverse Drug Reaction Reporting by Hospital Physicians : A Time Series Analysis in Spain

AbstractBackground: Spontaneous reporting of adverse drug reactions (ADRs) in hospitals is scarce and several obstacles to such reporting have been identified previously. Objective: To assess the effectiveness of a multifaceted intervention based on healthcare management agreements for improving spontaneous reporting of ADRs by physicians in a hospital setting. Methods: In 2003, the spontaneous reporting of ADRs was included as one of the objectives of hospital physicians at the Vall d’Hebron Hospital, Barcelona, Spain, within the context of management agreements between clinical services and hospital managers. A continuous intervention related to these management agreements, including periodic educational meetings and economic incentives, was then initiated. We carried out an ecological time series analysis and assessed the change in the total number of spontaneous reports of ADRs, and the number of serious ADRs, unexpected ADRs, and ADRs associated with new drugs between a period previous to the intervention (from 1998 to 2002) and the period during the intervention (from 2003 to 2005). A time series analysis with ARIMA (Auto-Regressive Integrated Moving Average) models was performed. Results: The median number of reported ADRs per year increased from 40 (range 23–55) in the first period to 224 (range 98–248) in the second period. In the first period, the monthly number of reported ADRs was stable (3.47 per month; 95% CI 1.90, 5.03), but in the second period the number increased progressively (increase of 0.74 per month; 95% CI 0.62, 0.86). In the second period, the proportion of reported serious ADRs increased nearly 2-fold (63.1% vs 32.5% in the first period). The absolute number of previously unknown or poorly known ADRs increased 4-fold in the second period (54 vs 13 in the first period). There was also an increase in the absolute number of suspected pharmacological exposures to new drugs (97 vs 28) and in the number of different new drugs suspected of causing ADRs (50 vs 19). Conclusion: A continuous intervention based on healthcare management agreements with economic incentives and educational activities is associated with a quantitative and qualitative improvement of spontaneous reporting of ADRs by hospital physicians.

Prevalence of pain in adults admitted to Catalonian hospitals: A cross-sectional study

Objective To survey the prevalence of pain in patients admitted to different hospitals of Catalonia and to describe which factors are related to pain.

G protein-coupled receptor oligomerization for what?

Although the G protein-coupled receptor (GPCR) oligomerization has been questioned during the last decade, under some premises the existence of a supramolecular organization of these receptors begins now to be widely accepted by the scientific community. Indeed, GPCR oligomers may enhance the diversity and performance by which extracellular signals are transferred to the G proteins in the process of receptor transduction, although the mechanism that underlie this phenomenon remains still unexplained. Recently, a trans-conformational switching model has been proposed as a mechanism allowing direct inhibition of receptor activation. Thus, heterotropic receptor–receptor allosteric regulations are behind the GPCR oligomeric function. Accordingly, we revise here how GPCR oligomerization impinge in several important receptor functions like biosynthesis, plasma membrane diffusion or velocity, pharmacology and signaling. Overall, the rationale of receptor oligomerization might lie in the cellular need of sensing complex extracellular signals and to translate into a simple computational mode.

Reporting randomised clinical trials of analgesics after traumatic or orthopaedic surgery is inadequate: a systematic review

BackgroundSeveral randomised clinical trials (RCTs) of analgesics in postoperative pain after traumatic or orthopaedic surgery (TOS) have been published, but no studies have assessed the quality of these reports. We aimed to examine the quality of reporting RCTs on analgesics for postoperative pain after TOS.MethodsReports of RCTs assessing analgesics in postoperative pain after TOS were systematically searched from electronic databases. The quality of reports was assessed using the CONSORT checklist (scoring range from 0 to 22). The quality was considered poor when scoring was 12 or lesser. The publication year and the impact factor of journals were recorded.ResultsA total of 92 reports of RCTs were identified and 69 (75%) scored 12 or lesser in CONSORT checklist (range 5-17). The mean (SD) CONSORT score of all reports was 10.6 (2.7). Missing CONSORT items included primary and secondary outcome measures (11%), the specific objectives and hypothesis definition (12%), the sample size calculation (12%), the dates defining the periods of recruitment (12%), the discussion of external validity of findings (14%), the allocation sequence generation (24%), and the interpretation of potential bias or imprecision of results (25%). There was a little improvement in CONSORT scores over time (r = 0.62; p < 0.001) and with impact factor of journals (r = 0.30; p < 0.001).ConclusionQuality of reporting RCTs on analgesics after TOS is poor. Reporting of those RCTs should be improved according to methodological standard checklists in the next years.

An Update on Adenosine A2A Receptors as Drug Target in Parkinson's Disease

Adenosine receptors are G protein-coupled receptors (GPCRs) that mediate the physiological functions of adenosine. In the central nervous system adenosine A(2A) receptors (A(2A)Rs) are highly enriched in striatopallidal neurons where they form functional oligomeric complexes with other GPCRs such us the dopamine D(2) receptor (D(2)R). Furthermore, it is assumed that the formation of balanced A(2A)R/D(2)R receptor oligomers are essential for correct striatal function as the allosteric receptor-receptor interactions established within the oligomer are needed for properly sensing adenosine and dopamine. Interestingly, A(2A)R activation reduces the affinity of striatal D(2)R for dopamine and the blockade of A(2A)R with specific antagonists facilitates function of the D(2)R. Thus, it may be postulated that A(2A)R antagonists are pro-dopaminergic agents. Therefore, A(2A)R antagonists will potentially reduce the effects associated with dopamine depletion in Parkinsons disease (PD). Accordingly, this class of compounds have recently attracted considerable attention as potential therapeutic agents for PD pharmacotherapy as they have shown potential effectiveness in counteracting motor dysfunctions and also displayed neuroprotective and anti-inflammatory effects in animal models of PD. Overall, we provide here an update of the current state of the art of these A(2A)R-based approaches that are under clinical study as agents devoted to alleviate PD symptoms.

Targeting striatal metabotropic glutamate receptor type 5 in Parkinson's disease: bridging molecular studies and clinical trials.

Metabotropic glutamate (mGlu) receptors are G protein-coupled receptors expressed primarily on neurons and glial cells modulating the effects of glutamatergic neurotransmission. The pharmacological manipulation of these receptors has been postulated to be valuable in the management of some neurological disorders. Accordingly, the targeting of mGlu5 receptors as a therapeutic approach for Parkinsons disease (PD) has been proposed, especially to manage the adverse symptoms associated to chronic treatment with classical PD drugs. Thus, the specific pharmacological blocking of mGlu5 receptors constitutes one of the most attractive non-dopaminergic-based strategies for PD management in general and for the L-DOPA-induced dyskinesia (LID) in particular. Overall, we provide here an update of the current state of the art of these mGlu5 receptor-based approaches that are under clinical study as agents devoted to alleviate PD symptoms.

Editorial Comment: European guidelines for low back pain - a necessary step forward and an opportunity not to be missed.

view of the three documents confirms that they will lead to a change in the current situation, but also shows that additional work is needed to achieve the declared goal of improving the quality and outcome of healthcare for this condition (www.backpaineurope.org). Assessment of the three COST documents with the instruments [7,9,11] used in previous systematic reviews [2,10], allows an evaluation according to standard criteria such as rigor in the development of the guidelines, as well as guarantees of the validity, clarity, strength, and applicability of the recommendations. With regard to rigor in development and guarantees of validity, the authors performed an excellent review of the available evidence from the viewpoint of identification, selection and updating, and highly accurate synthesis and grading of the evidence. The main weak point in these domains is the fact that the method used by the panel of experts to arrive at decisions is not clearly described. In addition, the guidelines for acute and chronic pain were not submitted to external peer review before their publication. These points are more relevant in the guidelines for chronic pain, since the main contributors of some chapters assessing the interventions used for this condition are precisely the “experts” in the field under review, a fact that could imply a higher degree of subjectivity in the judgements. With regard to the clarity of the recommendations, a very positive aspect is that the guidelines clearly indicate which interventions are not, or cannot be, recommended. Nevertheless, the terminology used in the recommendations for which there is stronger evidence sometimes includes rather ambiguous statements in addition to “recommended”, such as “consider using” as well as others (“can be recommended,” “may be recommended,” “can be considered,” and “should be considered”). This limitation is more relevant in the guidelines for chronic low back pain. Although some criteria (“known concerns”) were taken into account to separate the interventions into the categories “recommended” and “consider using”, it remains unclear which of them led to the final decision for cateJosep M. Arnau Ferran Pellisé Antoni Vallano Núria Prat