Effectiveness and safety of oral anticoagulants for non-valvular atrial fibrillation: a population-based cohort study in primary healthcare in Catalonia.

Objectives: Our objective was to analyse effectiveness and safety of oral anticoagulants (OAC) for stroke prevention in non-valvular atrial fibrillation. Material and methods: Population-based cohort study including adults initiating oral anticoagulants, either direct oral anticoagulants (DOAC) or vitamin K antagonists (VKA), during 2011-2020. Data source: SIDIAP, capturing information from the electronic health records of Primary Health Care in Catalonia, Spain. Study outcomes: stroke, cerebral and gastrointestinal (GI) haemorrhage, assessed by patients' subgroups according to different clinical characteristics. Results: We included 90,773 patients. Male sex, older than 75, previous event, peripheral artery disease, deep vein thrombosis, or receiving antiplatelets, antidiabetics or proton pump inhibitors (PPI) was associated with higher stroke risk. For DOAC-treated, treatment switch increased stroke risk, while being adherent had a protective effect. Men, antidiabetic treatment or a previous event increased the risk of cerebral bleeding. Receiving direct oral anticoagulants had a protective effect in comparison to vitamin K antagonists. For DOAC-treated, treatment switch increased, and adherence decreased the bleeding risk. Men, people with chronic kidney disease or a previous event posed an increased risk of gastrointestinal bleeding, whereas receiving PPI had a protective effect. For DOAC-treated, switch was associated with a higher bleeding risk. Conclusion: Being men, a previous event and DOAC-switch posed a higher risk for all study outcomes. direct oral anticoagulants had a protective effect against cerebral bleeding in comparison to vitamin K antagonists. Adherence to direct oral anticoagulants resulted in lower risk of stroke and cerebral bleeding. We found no differences in the risk of stroke and gastrointestinal bleeding when we compared direct oral anticoagulants vs. vitamin K antagonists.

Financing and Reimbursement of Approved Advanced Therapies in Several European Countries.

OBJECTIVES: The uncertainty in the cost-benefit of advanced therapy medicinal products (ATMPs) is a current challenge for their reimbursement in health systems. This study aimed to provide a comparative analysis of the National Health Authorities (NHAs) reimbursement recommendations issued in different European countries. METHODS: The NHA reimbursement recommendations for the approved ATMPs were compared among 8 European Union (EU) Countries (EU8: Ireland, England/Wales, Scotland, The Netherlands, France, Germany, Spain, and Italy). The search was carried out until December 31, 2021. RESULTS: A total of 19 approved ATMPs and 76 appraisal reports were analyzed. The majority of the ATMPs were reimbursed, although with uncertainty in added therapeutic value. No relationship between the type of the European Medicines Agency approval and reimbursement was found. Managed entry agreements, such as payment by results, were necessary to ensure market access. The main issue during the evaluation was to base the cost-effectiveness analyses on assumptions because of the limited long-term data. The estimated incremental cost-effectiveness ratio among countries reveals high variability. Overall, the median time to NHA recommendation for the EU8 is in the range of 9 to 17 months. CONCLUSIONS: Transparent, harmonized, and systematic assessments across the EU NHAs in terms of cost-effectiveness, added therapeutic value, and grade of innovativeness are needed. This could lead to a more aligned access, increasing the EU market attractiveness and raising public fairness in terms of patient access and pricing.

Dealing With Immunoglobulin Shortages: A Rationalization Plan From Evidence-Based and Data Collection.

Background: The demand and consumption of immunoglobulins (IgGs) are growing, and there are many difficulties in obtaining supplies. The aim of the study was to analyze the evolution of IgG consumption and cost over a decade, describe the measures implemented for clinical management in the context of regional public health system, and evaluate the initial impact of these measures. Methods: We performed a retrospective longitudinal study including patients of all public health systems in Catalonia. First, we analyzed data on consumption and cost of IgGs during a period between 1 January, 2010 and 31 December 2021. Second, we analyzed the impact of a set of regional measures in terms of annual consumption and cost of IgGs. Regional measures were based on rational evidence-based measures and computer registries. We compared the data of year before applying intervention measures (1 January and 31 December 2020) with data of year after applying clinical management interventions (1 January and 31 December 2021). In addition, detailed information on clinical indications of IgG use between 1 January and 31 December 2021 was collected. Results: Overall, in terms of population, the consumption of IgGs (g/1,000 inhabitants) increased from 40.4 in 2010 to 94.6 in 2021. The mean cost per patient increased from €10,930 in 2010 to €15,595 in 2021. After implementing the measures, the mean annual estimated consumption per patient in 2021 was statistically lower than the mean annual estimated consumption per patient in 2020 (mean difference -47 g, 95% CI -62.28 g, -31.72 g, p = 0.03). The mean annual estimated cost per patient in 2021 was also lower than the mean annual estimated cost per patient in 2020 (the mean difference was -€1,492, 95% CI -€2,132.12, -€851.88; p = 0.027). In 2021, according to evidence-based classification, 75.66% treatments were prescribed for a demonstrated therapeutic evidence-based indication, 12.17% for a developed therapeutic evidence-based indication, 4.66% for non-evidence-based therapeutic role indication, and 8.1% could not be classified because of lack of information. Conclusion: The annual consumption and cost of IgGs have grown steadily over the last decade in our regional public health system. After implementing a set of regional measures, the annual consumption of IgGs per patient and annual cost per patient decreased. However, the decrease has occurred in the context of the coronavirus disease 2019 (COVID-19) pandemic, which may have influenced their clinical use. Managing the use of IgGs through a rational plan with strategies including evidence-based and data collection may be useful in a shortage situation with growing demand. Registries play a key role in collection of systematic data to analyze, synthesize, and obtain valuable information for decision support. The action developed needs close monitoring in order to verify its effectiveness.

Current landscape of clinical development and approval of advanced therapies.

Advanced therapy medicinal products (ATMPs) are innovative therapies that mainly target orphan diseases and high unmet medical needs. The uncertainty about the product's benefit-risk balance at the time of approval, the limitations of nonclinical development, and the complex quality aspects of those highly individualized advanced therapies are playing a key role in the clinical development, approval, and post-marketing setting for these therapies. This article reviews the current landscape of clinical development of advanced therapies, its challenges, and some of the efforts several stakeholders are conducting to move forward within this field. Progressive iteration of the science, methodologically sound clinical developments, establishing new standards for ATMPs development with the aim to ensure consistency in clinical development, and the reproducibility of knowledge is required, not only to increase the evidence generation for approval but to set principles to achieve translational success in this field.

Chronic obstructive pulmonary disease (COPD) in Spain and the different aspects of its social impact: a multidisciplinary opinion document / Enfermedad Pulmonar Obstructiva Crónica (EPOC) y diferentes aspectos de su impacto social: un documento multidisciplinar de opinión

Chronic obstructive pulmonary disease (COPD) is one of the most prevalent diseases in the World, and one of the most important causes of mortality and morbidity. In adults 40 years and older, it affects more than 10% of the population and has enormous personal, family and social burden. Tobacco smoking is its main cause, but not the only one, and there is probably a genetic predisposition that increases the risk in some patients. The paradigm of this disease is changing in Spain, with an increase of women that has occurred in recent years. Many of the physio pathological mechanisms of this condition are well known, but the psychological alterations to which it leads, the impact of COPD on relatives and caregivers, the limitation of daily life observed in these patients, and the economic and societal burden that they represent for the health system, are not so well-known. A major problem is the high under-diagnosis, mainly due to difficulties for obtaining, in a systematic way, spirometries in hospitals and health-care centers. For this reason, the Fundación de Ciencias de la Salud and the Spanish National Network Center for Research in Respiratory Diseases (CIBERES) have brought together experts in COPD, patients and their organizations, clinical psychologists, experts in health economics, nurses and journalists to obtain their opinion about COPD in Spain. They also discussed the scientific bibliometrics on COPD that is being carried out from the CIBERES and speculated on the future of this condition. The format of the meeting consisted in the discussion of a series of questions that were addressed by different speakers and discussed until a consensus conclusion was reached

La enfermedad pulmonar obstructiva crónica (EPOC) es una de las enfermedades más prevalentes en el mundo y una de las causas más importantes de mortalidad y morbilidad. En los adultos de más de 40 años, afecta al menos al 10% de la población y tiene una enorme carga personal, familiar y social. El tabaquismo es su principal causa, pero no la única, y probablemente existe una predisposición genética que aumenta el riesgo en algunos pacientes. El paradigma de esta enfermedad está cambiando en España, con un aumento de la incidencia en mujeres que se ha producido en los últimos años. Muchos de los mecanismos fisiopatológicos de la EPOC son bien conocidos, pero no lo son tanto las alteraciones psicológicas a las que conduce, el impacto de la enfermedad en los familiares y cuidadores, la limitación de la vida cotidiana que se observa en estos pacientes y la carga económica y social que representan para el sistema sanitario. Un problema importante es el elevado infradiagnóstico, debido principalmente a las dificultades para obtener, de forma sistemática, espirometrías en los hospitales y centros de salud. Por este motivo, la Fundación de Ciencias de la Salud y el Centro de Investigación en Enfermedades Respiratorias (CIBERES) han reunido a expertos en EPOC, pacientes y sus organizaciones, psicólogos clínicos, expertos en economía de la salud, enfermeras y periodistas para obtener su opinión sobre la EPOC en España. También se ha hablado de la bibliometría científica sobre la EPOC que se está llevando a cabo desde el CIBERES y se ha especulado sobre el futuro de esta enfermedad. El formato de la reunión consistió en la discusión de una serie de cuestiones que fueron abordadas por diferentes ponentes y discutidas hasta llegar a una conclusión consensuada

Non-inferiority of dose reduction versus standard dosing of TNF-inhibitors in axial spondyloarthritis.

OBJECTIVE: The objective was to determine if dose reduction is non-inferior to full-dose TNFi to maintain low disease activity (LDA) in patients already in remission with TNFi, in axial spondyloarthritis. METHODS: Randomized, parallel, non-inferiority, open-label multicentre clinical trial. Patients were eligible if they had axial spondyloarthritis and had been in clinical remission for ≥ 6 months with any available TNFi (adalimumab, etanercept, infliximab, golimumab) at the dose recommended by product labelling. Patients were randomized by automated central allocation to continue the same TNFi dose schedule, or to reduce the dose by roughly half according to the protocol. The main outcome was the proportion of subjects with LDA after 1 year. Serious adverse reactions or infections were recorded. RESULTS: The trial stopped due to end of the funding period, after 126 patients were randomized; 113 patients (84.1% male, mean age (SD) 45.6 (13.0) years) were included in the main per-protocol subset. Non-inferiority was concluded for LDA at 1 year (47/55 (83.8%) patients in the full-dose and 48/58 (81.3%) patients in the reduced-dose arm, adjusted difference (95% CI) - 2.5% (- 16.6% to 11.7%)). Serious adverse reactions or infections were reported in 7/62 patients (11.3%) assigned to full dose and 2/61 patients (3.3%) assigned to reduced dose (p value = 0.164). CONCLUSION: In patients with ankylosing spondylitis in clinical remission for at least 6 months, dose reduction is non-inferior to full TNF inhibitor doses to maintain LDA after 1 year. Serious adverse events may be less frequent with reduced doses. TRIAL REGISTRATION: EU Clinical Trials Registry, EudraCT 2011-005871-18 and ClinicalTrials.gov, NCT01604629 .

Elderly patients treated with psychotropic medicines admitted to hospital: associated characteristics and inappropriate use.

PURPOSE: The purpose of this study is to describe the characteristics of older patients treated with psychotropic medicines and the associated factors and to assess their inappropriate use. METHODS: An observational, prospective study was carried out in 672 elderly patients admitted to seven hospitals for a year. A comparison of sociodemographic characteristics, geriatric variables, multimorbidity and the number of prescribed medicines taken in the preceding month before hospitalization between patients treated with psychotropics and those not treated was performed. To assess factors associated with psychotropics, multivariate logistic regression analyses were performed. Inappropriate use was assessed using the Beers and the STOPP criteria. RESULTS: A total of 57.5 % patients (median [Q1-Q3] age 81.7 [78.2-86.1], 65.7 % female) were treated with psychotropics (44.2 % anxiolytics, 22.6 % antidepressants and 10.8 % antipsychotics). Independent factors associated with the use of psychotropics were female gender (OR = 2.3; CI 95 %,1.6-3.5), some degree of disability on admission (slight [OR = 2.2; 1.2-4.2], moderate [OR = 3.2, 1.6-6.6], severe [OR = 3.4; 1.4-8] and very severe [OR = 5.1; 2.0-12.8]) and polypharmacy (5-9 medicines [OR = 3.0; 1.3-6.9] and ≥10 medicines [OR = 6.0; 2.7-13.6]). The associated factors varied depending on the different types of psychotropics. In patients treated with psychotropics, the percentage of those with at least one Beers (61.6 %) or at least one STOPP (71.4 %) criteria was significantly higher in comparison with those not treated with psychotropics (30.7 and 47.7 %, respectively, p < 0.001). CONCLUSIONS: Psychotropics are widely used in the elderly population and often their use is inappropriate. Female gender, a poor functional status and polypharmacy, are the characteristics linked to their use. Interventional strategies should be focused on patients with these characteristics.

Evaluation of dose reduction versus standard dosing for maintenance of remission in patients with spondyloarthritis and clinical remission with anti-TNF (REDES-TNF): study protocol for a randomized controlled trial.

BACKGROUND: Dose reduction schedules of tumor necrosis factor antagonists (anti-TNF) as maintenance therapy in patients with spondyloarthritis are used empirically in clinical practice, despite the lack of clinical trials providing evidence for this practice. METHODS/DESIGN: To address this issue the Spanish Society of Rheumatology (SER) and Spanish Society of Clinical Pharmacology (SEFC) designed a 3-year multicenter, randomized, open-label, controlled clinical trial (2 years for inclusion and 1 year of follow-up). The study is expected to include 190 patients with axial spondyloarthritis on stable maintenance treatment (≥4 months) with any anti-TNF agent at doses recommended in the summary of product characteristics. Patients will be randomized to either a dose reduction arm or maintenance of the dosing regimen as per the official labelling recommendations. Randomization will be stratified according to the anti-TNF agent received before study inclusion. Patient follow-up, visit schedule, and examinations will be maintained as per normal clinical practice recommendations according to SER guidelines. The study aims to test the hypothesis of noninferiority of the dose reduction strategy compared with standard treatment. The first patients were recruited in July 2012, and study completion is scheduled for the end of April 2015. DISCUSSION: The REDES-TNF study is a pragmatic clinical trial that aims to provide evidence to support a medical decision now made empirically. The study results may help inform clinical decisions relevant to both patients and healthcare decision makers. TRIAL REGISTRATION: EudraCT 2011-005871-18 (21 December 2011).

Utilización hospitalaria de medicamentos en condiciones diferentes a las aprobadas en la ficha técnica / Off-label drug use in hospitals

No disponible

Deciphering G protein-coupled receptor biology with fluorescence-based methods.

G-protein-coupled receptors (GPCRs) represent the main family of cell surface receptors and are virtually expressed in all eukaryotic cells. Interestingly, a large number of clinically used drugs exert their pharmacological effect via a GPCR, thus it seems crucial to deeply understand the biology of these receptors. The study of GPCR activation and signaling has been classically performed by physiological, biochemical and pharmacological approaches using radioactivity-based tools. However, apart from the potential hazards of radioisotope handling and environmental burden, these approaches have some technical limitations. Therefore, the development of fluorescence-based techniques in general and fluorescence and bioluminescence resonance energy transfer (FRET and BRET) in particular have revolutionized the way to study GPCR functioning both in vitro and in vivo. Indeed, these techniques allow the characterization and visualization of all the individual GPCR signaling steps (i.e. ligand binding, receptor activation, G-protein coupling, G-protein activation, GPCR desensitization) with high temporal and spatial resolution. Here, we review the use and impact of fluorescent-based methodologies on the deciphering of GPCR biology.

Prevalence, risk factors and main features of adverse drug reactions leading to hospital admission.

PURPOSE: To assess the prevalence of hospital admission related to adverse drug reactions (ADRs) in a third-level hospital, to analyse the associated factors, and to describe the reactions and the drugs involved. METHODS: A cross-sectional study was conducted for a 120-day period. Patients that were urgently hospitalized entered the study. The primary endpoint was the ADR-related urgent admission. A descriptive analysis of demographic, clinical, and drug-related variables was performed. The association between the likelihood of urgent admission due to ADRs and age, gender, and number of drugs used was analysed. A descriptive analysis of the suspected drugs and the reactions in ADR-related admissions was performed. RESULTS: Overall, 186 out of 4,403 hospital admissions were due to ADRs (prevalence: 4.2 % [95 % CI 3.7-4.8 %]). Age (≥65 years: OR 1.59 [95 % CI 1.10-2.29]) and number of drugs used at the time of admission (3-5 drugs: OR 5.07 [95 % CI 2.71-9.59]; 6-9 drugs: OR 5.90 [95 % CI 3.16-11.0]; ≥10 drugs: OR 8.94 [95 % CI 4.73-16.89]), but not gender, were identified as independent factors associated with ADR-related hospitalization. The overall in-hospital stay for patients admitted with ADRs amounted to 1,785 days. The ADRs were mainly type A reactions (92 %). Acute renal failure related to renin-angiotensin system inhibitors, haemorrhage due to anticoagulants, and upper gastrointestinal bleeding related to antiplatelet drugs and/or non-steroidal anti-inflammatory drugs were the most frequent. CONCLUSION: Over 4 % of urgent hospitalizations are caused by ADRs, which are dose-related and predictable in more than 90 % of cases. The main risk factors are advanced age and polypharmacy.

A quick diagnosis unit as an alternative to conventional hospitalization in a tertiary public hospital: a descriptive study.

INTRODUCTION:  Reports indicate that a significant number of patients admitted to internal medicine units could be studied on an outpatient basis. OBJECTIVES:  This article assesses a quick diagnosis unit (QDU) as an alternative to acute hospitalization for the diagnostic study of patients with potentially serious diseases and suspected malignancy.  PATIENTS AND METHODS:  Between March 2008 and June 2012, 1226 patients were attended by the QDU. Patients were referred from the emergency department, primary health care centers, and outpatient clinics according to well­defined criteria. Clinical information was prospectively registered in a database.  RESULTS:  There were 634 men (51.7%), with a mean age of 60.5 ±17.5 years. The mean time to the first visit was 3.5 ±5.3 days. Most patients (65.7%) required only 2 visits. The mean interval to diagnosis was 12.2 ±14.7 days. A total of 324 patients (26.4%) had cancer. The diagnosis was  solid tumor in 81.5% of the cases, lymphoma in 19.8%, and various hematologic malignancies in 4.3%. The second most common diagnosis was anemia not associated with cancer (8.6% of the cases). Admission to the QDU allowed to avoid conventional hospitalization for diagnostic studies in 71.5% of the patients, representing a mean freeing­up rate of 7 internal medicine beds per day. In a satisfaction survey, 97% of the patients were completely or very satisfied and 96% preferred the QDU to conventional hospitalization.  CONCLUSIONS:  A QDU may be a feasible alternative to conventional hospitalization for the diagnosis of otherwise healthy patients with suspected severe disease. Appropriately managed and supported, QDUs can lighten the burden of emergency departments and reduce the need for hospitals beds.

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 Parkinson's 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.

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.

BACKGROUND: Several 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. METHODS: Reports 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. RESULTS: A 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). CONCLUSION: Quality 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 intervention to improve spontaneous adverse drug reaction reporting by hospital physicians: a time series analysis in Spain.

BACKGROUND: 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.

Trends in lithium prescription in Spain from 1985 to 2003.

Lithium use for bipolar disorder has decreased in the United States. We aimed at studying lithium prescription in Spain from 1985 to 2003. Prescription data, expressed in daily defined dose per 1,000 inhabitants per day, were obtained. Lithium prescription increased uninterruptedly from 0.21 to 0.79 DID. The psychiatric reform in Spain and a broader definition of BD during the last decades are possible explanations for this rise.

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.