Study of the strength of the evidence and the redundancy of the research on pharmacological treatment for Alzheimer's disease: a cumulative meta-analysis and trial sequential analysis.

PURPOSE: To study the strength of the evidence on efficacy, safety and acceptability of cholinesterase inhibitors (ChEI) and memantine for Alzheimer's disease (AD); and to determine the number of redundant post-authorisation trials. METHODS: A cumulative meta-analysis with a trial sequential analysis (TSA) was performed. Primary outcomes were cognitive function assessed with ADAS-cog or SIB scales, discontinuation due to adverse events (AE) and discontinuation for any reason. The redundancy of post-authorisation clinical trials was studied by determining the novel aspects of each study on patient, intervention, comparator and trial outcome characteristics. Two criteria of futile trial (lenient and strict) were used. RESULTS: A total of 63 randomised clinical trials (RCTs) (16,576 patients) were included. It was conclusive that neither ChEI nor memantine achieved clinically significant improvement in cognitive function. In relation to safety, there was sufficient evidence to conclude that donepezil caused a clinically relevant increase on dropouts due to AE whereas the evidence was inconclusive for the remaining interventions. Regarding acceptability, it was conclusive that no ChEI improved treatment discontinuation while it was uncertain for memantine. The proportion of redundant trials was 5.6% with the lenient criteria and 42.6% with the strict one. CONCLUSIONS: The evidence is conclusive that ChEI and memantine do not achieve clinically significant symptomatic improvement in AD while the acceptability of ChEI is unsatisfactory. Although evidence on the safety of pharmacological interventions for AD and acceptability of memantine is inconclusive, no further RCTs are needed as their efficacy is not clinically relevant. Redundant trials were identified but their number depends on the criteria of futility used.

Measuring anticholinergic exposure in patients with dementia: A comparative study of nine anticholinergic risk scales.

OBJECTIVE: To describe the prevalence and concordance of anticholinergic exposure according to 9 published scales, to quantify the relative weight of the drug subtypes included in each scale, and to identify clinical variables related to anticholinergic exposure. METHODS: Observational and cross-sectional study using 5323 cases of dementia diagnosed in the 7 hospitals of the public health care system of the Health Region of Girona (Spain) between 2007 and 2014 and registered by the Registry of Dementias of Girona (ReDeGi). We used the Pharmacy database that includes all the drugs prescribed by specialist and primary care physicians and dispensed in pharmacies. We calculated the anticholinergic exposure using the scoring rules of each scale. Age, gender, place of residence, dementia subtype, Clinical Dementia Rating score, Mini-Mental Status Examination score, and Blessed Dementia Rating Score at the moment of dementia diagnose were retrieved from the ReDeGi. RESULTS: Prevalence of the annual anticholinergic exposure ranged from 36.3% to 69.0% according to the different scales, the concordance among scales was poor to moderate, and the central nervous system drugs accounted the most for anticholinergic exposure. Being in a nursing home, having depressive symptoms, having a non-Alzheimer's dementia subtype, the number of drug treatments, and the severity of dementia were main determinants of anticholinergic exposure. CONCLUSIONS: There is a large difference in outcomes among the 9 anticholinergic risk scales. Clinicians and researchers should be aware of these differences when using these instruments in patients with dementia.

Predictors of discontinuation, efficacy, and safety of memantine treatment for Alzheimer's disease: meta-analysis and meta-regression of 18 randomized clinical trials involving 5004 patients.

BACKGROUND: The risk-benefit relationship of memantine treatment for Alzheimer's disease (AD) remains unclear. In addition, variability between the results of clinical trials has been observed. The aim of this study was to investigate the risk-benefit relationship of memantine treatment in patients with AD and to determine the predictor effect of patient, intervention, and study design related covariates. METHODS: A systematic review and meta-analysis of double-blind, placebo controlled clinical trials was performed. Primary outcomes were all-cause discontinuation, discontinuation due to adverse events (AE) and efficacy on cognitive function. Odds ratio (OR) and standard mean difference (SMD) with 95% confidence intervals were calculated. Meta-regression was conducted to identify related covariates. Cochrane Collaboration tool was used to evaluate the risk of bias of included trials. RESULTS: Eighteen studies involving 5004 patients were included. No differences between memantine and placebo were found for all-cause treatment discontinuation (OR=0.97 [0.82, 1.14]) and discontinuation due to AE (OR=1.18 [0.91, 1.53]). Memantine showed small improvement on cognitive function (SMD=0.15 [0.08, 0.22]). Baseline functional ability was positively associated with all-cause treatment discontinuation and discontinuation due to AE. CONCLUSIONS: Our study suggests that memantine has a very small efficacy on AD symptomatology and its safety profile is similar to that of placebo. No evidence of treatment discontinuation improvement with memantine is found, indicating a dubious risk-benefit relationship. No intervention characteristic or subgroup of patients clearly shows a significantly better risk-benefit relationship. PROSPERO REGISTRATION: CRD42014015696 .

Discontinuation, Efficacy, and Safety of Cholinesterase Inhibitors for Alzheimer's Disease: a Meta-Analysis and Meta-Regression of 43 Randomized Clinical Trials Enrolling 16 106 Patients.

Background: We investigated the effect of cholinesterase inhibitors on all-cause discontinuation, efficacy and safety, and the effects of study design-, intervention-, and patient-related covariates on the risk-benefit of cholinesterase inhibitors for Alzheimer's disease. Methods: A systematic review and meta-analysis of randomized placebo-controlled clinical trials comparing cholinesterase inhibitors and placebo was performed. The effect of covariates on study outcomes was analysed by means of meta-regression using a Bayesian framework. Results: Forty-three randomized placebo-controlled clinical trials involving 16106 patients were included. All-cause discontinuation was higher with cholinesterase inhibitors (OR = 1.66), as was discontinuation due to adverse events (OR=1.75). Cholinesterase inhibitors improved cognitive function (standardized mean difference = 0.38), global symptomatology (standardized mean difference=0.28) and functional capacity (standardized mean difference=0.16) but not neuropsychiatric symptoms. Rivastigmine was associated with a poorer outcome on all-cause discontinuation (Diff OR = 1.66) and donepezil with a higher efficacy on global change (Diff standardized mean difference = 0.41). The proportion of patients with serious adverse events decreased with age (Diff OR = -0.09). Mortality was lower with cholinesterase inhibitors than with placebo (OR = 0.65). Conclusion: While cholinesterase inhibitors show a poor risk-benefit relationship as indicated by mild symptom improvement and a higher than placebo all-cause discontinuation, a reduction of mortality was suggested. Intervention- and patient-related factors modify the effect of cholinesterase inhibitors in patients with Alzheimer's disease.

Effectiveness and safety of drugs used for stroke prevention in a cohort of non-valvular atrial fibrillation patients from a primary care electronic database.

PURPOSE: The aim of this study was to assess effectiveness and safety of antithrombotics for stroke prevention in non-valvular atrial fibrillation in real-use conditions. METHODS: We used a population-based retrospective cohort study. Information emerges from SIDIAP, a database containing anonymized information from electronic health records from 274 primary healthcare centres of the Catalan Health Institute, Catalonia (Spain), with a reference population of 5 835 000 people. Population includes all adults with a new diagnosis of non-valvular atrial fibrillation registered in SIDIAP from 2007 to 2012. The main outcome of antithrombotics' effectiveness was stroke. The main outcomes of safety were cerebral and gastrointestinal haemorrhages. We also estimated all-cause mortality. We used multivariable Cox proportional hazard models to examine association between antithrombotic treatment and main outcomes. RESULTS: We included 22 205 subjects with non-valvular atrial fibrillation; 40.8% initiated on vitamin K antagonists (VKA), 33.4% on antiplatelets and 25.8% untreated. We found stroke-risk reduction with VKA, hazard ratio (HR) 0.72 (95% confidence interval (CI), 0.58-0.91), also seen in patients with CHADS2 ≥ 2, HR 0.65 (95%CI, 0.49-0.86), and CHA2 DS2 -VASc ≥ 2, HR 0.66 (95%CI, 0.52-0.84). We observed a higher risk of digestive bleeding with antiplatelets, HR 1.32 (95%CI, 1.01-1.73). Both VKA and antiplatelets were associated with reduction of all-cause mortality risk; HR 0.55 (95%CI, 0.49-0.62) and HR 0.89 (95%CI, 0.80-0.97), respectively. CONCLUSIONS: This study found a stroke-risk reduction associated with VKA and an increased risk of gastrointestinal bleeding associated with platelet-aggregation inhibitors in comparison with untreated patients. Both antithrombotic groups showed a reduction in all-cause mortality. Copyright © 2016 John Wiley & Sons, Ltd.

Psychostimulant drugs for cocaine dependence.

BACKGROUND: Cocaine dependence is a severe disorder for which no medication has been approved. Like opioids for heroin dependence, replacement therapy with psychostimulants could be an effective therapy for treatment. OBJECTIVES: To assess the effects of psychostimulants for cocaine abuse and dependence. Specific outcomes include sustained cocaine abstinence and retention in treatment. We also studied the influence of type of drug and comorbid disorders on psychostimulant efficacy. SEARCH METHODS: This is an update of the review previously published in 2010. For this updated review, we searched the Cochrane Drugs and Alcohol Group Trials Register, CENTRAL, MEDLINE, Embase and PsycINFO up to 15 February 2016. We handsearched references of obtained articles and consulted experts in the field. SELECTION CRITERIA: We included randomised parallel group controlled clinical trials comparing the efficacy of a psychostimulant drug versus placebo. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 26 studies involving 2366 participants. The included studies assessed nine drugs: bupropion, dexamphetamine, lisdexamfetamine, methylphenidate, modafinil, mazindol, methamphetamine, mixed amphetamine salts and selegiline. We did not consider any study to be at low risk of bias for all domains included in the Cochrane 'Risk of bias' tool. Attrition bias was the most frequently suspected potential source of bias of the included studies. We found very low quality evidence that psychostimulants improved sustained cocaine abstinence (risk ratio (RR) 1.36, 95% confidence interval (CI) 1.05 to 1.77, P = 0.02), but they did not reduce cocaine use (standardised mean difference (SMD) 0.16, 95% CI -0.02 to 0.33) among participants who continued to use it. Furthermore, we found moderate quality evidence that psychostimulants did not improve retention in treatment (RR 1.00, 95% CI 0.93 to 1.06). The proportion of adverse event-induced dropouts and cardiovascular adverse event-induced dropouts was similar for psychostimulants and placebo (RD 0.00, 95% CI -0.01 to 0.01; RD 0.00, 95% CI -0.02 to 0.01, respectively). When we included the type of drug as a moderating variable, the proportion of patients achieving sustained cocaine abstinence was higher with bupropion and dexamphetamine than with placebo. Psychostimulants also appeared to increase the proportion of patients achieving sustained cocaine and heroin abstinence amongst methadone-maintained, dual heroin-cocaine addicts. Retention to treatment was low, though, so our results may be compromised by attrition bias. We found no evidence of publication bias. AUTHORS' CONCLUSIONS: This review found mixed results. Psychostimulants improved cocaine abstinence compared to placebo in some analyses but did not improve treatment retention. Since treatment dropout was high, we cannot rule out the possibility that these results were influenced by attrition bias. Existing evidence does not clearly demonstrate the efficacy of any pharmacological treatment for cocaine dependence, but substitution treatment with psychostimulants appears promising and deserves further investigation.

Phlebotonics for venous insufficiency.

BACKGROUND: Chronic venous insufficiency (CVI) is a common condition caused by valvular dysfunction with or without associated obstruction, usually in the lower limbs. It might result in considerable discomfort with symptoms such as pain, itchiness and tiredness in the legs. Patients with CVI may also experience swelling and ulcers. Phlebotonics are a class of drugs often used to treat CVI. This is an update of a review first published in 2005. OBJECTIVES: To assess the efficacy and safety of phlebotonics administered both orally and topically for treatment of signs and symptoms of lower extremity CVI. SEARCH METHODS: For this update, the Cochrane Vascular Trials Search Co-ordinator (TSC) searched the Specialised Register (August 2015), as well as the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 7). The reference lists of the articles retrieved by electronic searches were searched for additional citations. We also contacted pharmaceutical companies and searched the World Health Organization (WHO) International Clinical Trials Registry Platform Search Portal for ongoing studies (last searched in August 2015). SELECTION CRITERIA: Randomised, double-blind, placebo-controlled trials (RCTs) assessing the efficacy of rutosides, hidrosmine, diosmine, calcium dobesilate, chromocarbe, Centella asiatica, disodium flavodate, french maritime pine bark extract, grape seed extract and aminaftone in patients with CVI at any stage of the disease. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the quality of included RCTs. We estimated the effects of treatment by using risk ratios (RRs), mean differences (MDs) and standardised mean differences (SMDs), according to the outcome assessed. We calculated 95% confidence interval (CIs) and percentage of heterogeneity (I(2)). Additionally, we performed sensitivity analyses. MAIN RESULTS: We included 66 RCTs of oral phlebotonics, but only 53 trials provided quantifiable data (involving 6013 participants; mean age 50 years) for the efficacy analysis: 28 for rutosides, 10 hidrosmine and diosmine, nine calcium dobesilate, two Centella asiatica, two aminaftone, two french maritime pine bark extract and one grape seed extract. No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria.Moderate-quality evidence suggests that phlebotonics reduced oedema in the lower legs compared with placebo. Phlebotonics showed beneficial effects among participants including reduced oedema (RR 0.70, 95% CI 0.63 to 0.78; I(2) = 20%; 1245 participants) and ankle circumference (MD -4.27 mm, 95% CI -5.61 to -2.93 mm; I(2) = 47%; 2010 participants). Low-quality evidence reveals no difference in the proportion of ulcers cured with phlebotonics compared with placebo (RR 0.94, 95% CI 0.79 to 1.13; I(2) = 5%; 461 participants). In addition, phlebotonics showed greater efficacy for trophic disorders, cramps, restless legs, swelling and paraesthesia, when compared with placebo. We identified heterogeneity for the variables of pain, itching, heaviness, quality of life and global assessment by participants. For quality of life, it was not possible to pool the studies because heterogeneity was high. However, high-quality evidence suggests no differences in quality of life for calcium dobesilate compared with placebo (MD -0.60, 95% CI -2.15 to 0.95; I(2) = 40%; 617 participants), and low-quality evidence indicates that in the aminaftone group, quality of life was improved over that reported in the placebo group (MD -10.00, 95% CI -17.01 to - 2.99; 79 participants). Moderate-quality evidence shows that the phlebotonics group had greater risk of non-severe adverse events than the placebo group (RR 1.21, 95% CI 1.05 to 1.41; I(2) = 0; 3975 participants). Gastrointestinal disorders were the most frequently reported adverse events. AUTHORS' CONCLUSIONS: Moderate-quality evidence shows that phlebotonics may have beneficial effects on oedema and on some signs and symptoms related to CVI such as trophic disorders, cramps, restless legs, swelling and paraesthesia when compared with placebo but can produce more adverse effects. Phlebotonics showed no differences compared with placebo in ulcer healing. Additional high-quality RCTs focused on clinically important outcomes are needed to improve the evidence base.

Frequency of ambulatory care adverse events in Latin American countries: the AMBEAS/PAHO cohort study.

OBJECTIVE: Determine the frequency and preventability of adverse events (AEs) from available information sources in selected ambulatory care (AC) sites in Latin America (LA). DESIGN: Multinational observational cohort was conducted to determine the period prevalence (retrospective focus) and the cumulative incidence (prospective focus) of AEs. SETTING: Outpatient clinics in Mexico, Peru, Brazil and Colombia. PARTICIPANTS: A random selection of 2080 patients. INTERVENTIONS: The existence of AE was decided based on trigger information provided by the patient and crossing the data with each patient's medical history. MAIN OUTCOME MEASURES: AE occurrences 6 months prior (prevalence) and 42 days after (incidence) the patient receiving AC were identified. AE type and preventability were also described. RESULTS: Two thousand eighty patients participated in the study. AEs prevalence was 5.2% (108/2080) [95% confidence interval (CI) 4.2-6.1%], and cumulative incidence was 2.4% (42/1757) (95% CI 1.7-3.1%). AEs considered preventable were 44% (55/108) of prevalence period, and 52.4% (22/42) of incidence period. Preventability was associated with patient socioeconomic status (OR 3.5, 95% CI 1.4-8.8), medication error (OR 0.1, 95% CI 0.0-0.4), diagnostic error (OR 0.1, 95% CI 0.0-0.8) and a minor impact on the patient (OR 0.2 95% CI 0.1-0.9). CONCLUSION: The frequency of AE in ambulatory settings in LA is in the high-frequency range of research focused on the prevalence of AEs. Fifty percent was preventable. This study provides an approach for assessing the frequency and preventability of AE in order to enhance patient safety in LA.

Treatment discontinuation with methylphenidate in adults with attention deficit hyperactivity disorder: a meta-analysis of randomized clinical trials.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) in adulthood is increasingly diagnosed and treated. Methylphenidate is frequently advocated as a first-line pharmacological treatment. PURPOSE: The aim of our study was to compare all-cause discontinuation rate of methylphenidate and its pharmaceutical presentations with placebo in adults with ADHD. METHODS: This was a systematic review and meta-analysis of randomized controlled trials comparing methylphenidate with placebo in adults with ADHD. All-cause treatment discontinuation was the primary endpoint. The efficacy in reducing ADHD symptoms and safety were the secondary endpoints. RESULTS: Twelve studies (2,496 patients) met the inclusion criteria. Four racemic methylphenidate and one dexmethylphenidate presentations were investigated. The rate of all-cause treatment discontinuation was greater with methylphenidate than with placebo, but this difference was not statistically significant [odds ratio (OR) 1.19, 95 % confidence interval (95 % CI) 0.82-1.74, P = 0.37, I(2) = 64 %] This finding reached the conventional threshold of statistical significance after one outlier study was excluded (OR 1.44, 95 % CI 1.14-1.82, P = 0.002, I(2) = 0). Methylphenidate was more efficacious than placebo for reducing ADHD symptoms and it was associated with a higher proportion of patients dropping out due to adverse effects. CONCLUSIONS: Despite reducing ADHD symptoms, methylphenidate showed no advantage over placebo in terms of treatment discontinuation. More attention should be given in the future to the endpoint "all-cause treatment discontinuation" when making regulatory decisions and developing clinical guidelines involving the treatment of ADHD in adulthood.

Atomoxetine for attention deficit hyperactivity disorder in the adulthood: a meta-analysis and meta-regression.

PURPOSE: Atomoxetine is a non-stimulant drug that could be an alternative to methylphenidate, whose benefit : risk balance for the treatment of adults with attention deficit hyperactivity disorder (ADHD) has recently been shown to be unclear. This study aimed to compare all-cause discontinuation rate between atomoxetine and placebo in adults with ADHD. Secondarily, efficacy and safety were investigated. METHODS: Systematic review and meta-analysis of randomized controlled trials comparing atomoxetine with placebo in adults with ADHD were performed. All-cause treatment discontinuation was the primary endpoint. Efficacy in reducing ADHD symptoms and safety were the secondary endpoints. Odds ratio (OR) and the standardized mean difference (SMD) were calculated for dichotomous and continuous outcomes, respectively. Data were pooled using the fixed and random effects model. The influence of study design-related, intervention-related and patient-related co-variables over the primary endpoint was investigated by means of meta-regression. This study is registered with the international prospective register of systematic reviews (PROSPERO): CRD 42012002042. RESULTS: Twelve studies (3375 patients) were included. Treatment discontinuation was larger with atomoxetine than with placebo (OR = 1.39). No co-variable was found to modify the effect of atomoxetine over treatment discontinuation. Atomoxetine showed modest efficacy in reducing ADHD symptoms irrespective of the assessor: patient (SMD = -0.33); clinician (SMD = -0.40). The rate of adverse events-induced discontinuation was higher with atomoxetine than with placebo (OR = 2.57). CONCLUSION: This study suggests that atomoxetine has a poor benefit-risk balance for the treatment of adults with ADHD. The recommendation of atomoxetine use in this population is weak.

Efficacy of psychostimulant drugs for amphetamine abuse or dependence.

BACKGROUND: Amphetamine dependence is a public health problem with medical, psychiatric, cognitive, legal and socioeconomic consequences. To date, no pharmacological treatment has been approved for this disorder, and psychotherapy remains the mainstay of treatment. In recent years, psychostimulants have been investigated as a possible replacement therapy. OBJECTIVES: To evaluate the efficacy and safety of psychostimulant medications for amphetamine abuse or dependence. The influences of type of drug, type of dependence, comorbid disorders, clinical trial risk of bias and publication of data were also studied. SEARCH METHODS: Relevant trials were searched in the following sources: PubMed (January 1966 to 6 June 2012), EMBASE (January 1988 to 6 June 2012), CENTRAL (The Cochrane Library, Issue 5 of 12, May 2012), PsycINFO (January 1985 to 6 June 2012) and the Specialised Register of the Cochrane Drug and Alcohol Group (June 2012). We also searched the reference lists of retrieved trials, the list of studies citing the included trials and the main electronic registers of ongoing trials (ClinicalTrials.gov, International Clinical Trials Registry Platform and EU Clinical Trials Register). Finally, we contacted investigators to request information about unpublished trials. Searches included non-English language literature. SELECTION CRITERIA: All randomised, placebo-controlled, parallel-group clinical trials investigating the efficacy or safety of psychostimulants for amphetamine dependence or abuse conducted in an outpatient setting. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: Eleven studies were included in the review (791 participants). Studied psychostimulants included dexamphetamine, bupropion, methylphenidate and modafinil. No significant differences were found between psychostimulants and placebo for any of the studied efficacy outcomes. Overall retention in studies was low (50.4%). Psychostimulants did not reduce amphetamine use (mean difference (MD) -0.26, 95% confidence interval (CI) -0.85 to 0.33) or amphetamine craving (MD 0.07, 95% CI -0.44 to 0.59) and did not increase sustained abstinence (relative risk (RR) 1.12, 95% CI 0.84 to 1.49). The proportion of adverse events inducing dropout was similar for psychostimulants and placebo (risk difference (RD) 0.01, 95% CI -0.03 to 0.04). The main findings did not change in any subgroup analysis. AUTHORS' CONCLUSIONS: Results of this review do not support the use of psychostimulant medications at the tested doses as a replacement therapy for amphetamine abuse or dependence. Future research could change this conclusion, as the numbers of included studies and participants are limited and information on relevant outcomes, such as efficacy according to the severity of dependence or craving, is still missing.

Drug-induced Sudden Death: A Scoping Review.

BACKGROUND: The risk of sudden cardiac death (SCD) can be increased with the use of drugs. However, it has been described heterogeneously in the literature. OBJECTIVE: This study aims to systematically review epidemiological studies dealing with druginduced sudden death, describe their methodologies, and summarize the results found. METHODS: A scoping review has been carried out using Medline electronic database. The search was limited up to 2020. Epidemiological studies were included, and case reports or case series were excluded. RESULTS: Out of 3,114 potential articles, 74 were included. Most studies originated from North America (40.5%) or Europe (39.2%). Case-control (47.3%) or cohort (40.5%) studies were the most common designs. The data for outcomes and exposure were retrieved mainly from administrative databases (37.8%) or medical charts/hospital discharge reports (32.4%), but most studies used several sources of information. A composite variable of sudden death or SCD, mainly with ventricular arrhythmia, was the most frequently used endpoint. Only 18.9% of the studies included autopsy results to confirm the death. Psychotropic drugs were the most frequently studied. An increased risk of different outcomes for typical antipsychotics, tricyclic antidepressants, domperidone, and antiepileptics is suggested. CONCLUSION: The methodologies used were highly heterogeneous, and the results were, in general, not conclusive. An improvement of the methodologies is needed to achieve a conclusion regarding the risk of SCD associated with drug use.

[Risk perception, information received and occupational engagement of workers in a university hospital in the face of the COVID-19 pandemic.] / Percepción del riesgo, información recibida y participación laboral de los trabajadores de un hospital universitario ante la pandemia de la COVID-19.

OBJECTIVE: Hospital workers faced the pandemic with a lack of knowledge, procedures and resources, which generated different experiences based on the perceived risk of exposure. It was considered pertinent to conduct a study to learn about the risk perception, the information received and the occupational engagement of workers in a university hospital in the face of the pandemic. METHODS: A cross-sectional study (july-september 2020) was carried out by an ad hoc survey of workers in the Majadahonda Puerta de Hierro University Hospital with 20 items (Likert scale from 0=not at all agree to 5=totally agree). The sample size was set at 828 workers. The absolute frequency and percentage of agreement for each item were described. Chi-Square was used to assess the association of responses with sex, type of worker, work area and activity in COVID-19 units. RESULTS: 992 workers participated, with 80.7% being women, 79.8% healthcare personnel and 33.2% nurses. Workers perceived a high risk of exposure. Approximately half confirmed that they had received information on the use of masks, although not on PPE. More than half stated that they felt involved in teamwork, but not in COVID-19 unit planning. Statistically significant differences (p<0.05) were found in the risk perception by sex, between type of worker (healthcare vs. non-healthcare), work area (healthcare vs. non-healthcare) and working in COVID-19 Units vs. non-COVID-19 Units. CONCLUSIONS: Healthcare personnel who worked in care areas and COVID-19 units present greater perception of the risk of exposure, although they report a higher degree of agreement in the information received and in their work engagement in the face of the pandemic.

OBJETIVO: Los trabajadores del hospital afrontaron la pandemia con falta de conocimientos, procedimientos y recursos, lo que generó diferentes experiencias en base al riesgo de exposición percibido. Se consideró pertinente realizar un estudio para conocer la percepción del riesgo, la información recibida y la participación laboral de los trabajadores de un hospital universitario ante la pandemia. METODOS: Se realizó un estudio transversal (entre julio y septiembre de 2020) mediante una encuesta ad hoc con 20 ítems (Escala Likert de 0=nada de acuerdo a 5=totalmente de acuerdo) a los trabajadores del Hospital Universitario Puerta de Hierro Majadahonda, que desarrollaron su actividad laboral durante la primera ola pandémica de la COVID-19. El tamaño muestral se estableció en 828 sujetos. Se describieron la frecuencia absoluta y el porcentaje de acuerdo de cada ítem. Se usó la chi-cuadrado para valorar la asociación de las respuestas con el sexo, el tipo de trabajador, el área de trabajo y la actividad en unidades de COVID-19. RESULTADOS: Participaron 992 trabajadores, habiendo un 80,7% de mujeres, un de 79,8% personal sanitario y un 33,2% de enfermeras. Los trabajadores percibieron un alto riesgo de exposición. Aproximadamente la mitad afirmaron haber recibido información sobre el uso de mascarillas, aunque no de los equipos de protección individual (EPI). Más de la mitad afirmó sentirse partícipe del trabajo en equipo, pero no de la planificación de unidades de COVID-19. Se encontraron diferencias estadísticamente significativas (<0,05) en la percepción del riesgo por sexo, entre el tipo de trabajador (sanitario frente a no sanitario), el área de trabajo (asistencial frente a no asistencial) y trabajar en Unidades de COVID-19 frente a Unidades de no COVID-19. CONCLUSIONES: Los sanitarios que trabajaron en áreas asistenciales y unidades de COVID-19 presentan mayor percepción del riesgo de exposición, aunque refieren mayor grado de acuerdo en la información recibida y en su participación laboral ante la pandemia.

Effects of selective serotonin reuptake inhibitors and other antidepressant drugs on the risk of hip fracture: a case-control study in an elderly Mediterranean population.

OBJECTIVES: To describe the association between exposure to different antidepressant drugs and hip fracture in an elderly Mediterranean population. METHODS: Cases were all patients aged 50-95 years admitted to the emergency room of our hospital with hip fracture not related to a high intensity trauma during 2010. For each case, four controls were identified from primary care electronic medical records matched by age (±3 years), gender, date of consultation at the primary care centre (±1 month) and primary care centre. Pharmacological treatments received within the previous 5 years were retrieved from the prescription records. Crude and adjusted risks associated with exposures were calculated by conditional logistic regression. ORs were adjusted by matching variables and by significant risk factors identified in the bivariate analysis (prescription of ≥4 drugs, osteoporosis, diabetes mellitus and previous fracture). RESULTS: 136 cases and 544 controls were analysed. Adjusted OR (95% CI) for hip fracture associated with exposure to any antidepressants was 2.42 (1.24 to 4.73); for selective serotonin reuptake inhibitors (SSRIs) it was 3.52 (1.67 to 7.41), for non-selective monoamine reuptake inhibitors 1.07 (0.18 to 6.46) and for other antidepressants 0.82 (0.27 to 2.48). Sertraline (OR 3.88 (1.15 to 13.09)) was the only active principle with significant adjusted risk. When only exposures >6 months were considered, significant risks persisted for SSRIs (OR 2.64 (1.10 to 6.37)). CONCLUSIONS: The results of this study are coincident with other studies in which SSRIs, but not other types of antidepressants, are associated with an increased risk of hip fracture in our setting.

Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting.

AIMS: Despite progress in anti-emetic treatment, many patients still suffer from chemotherapy-induced nausea and vomiting (CINV). This is a pilot, randomized, double-blind, placebo-controlled phase II clinical trial designed to evaluate the tolerability, preliminary efficacy, and pharmacokinetics of an acute dose titration of a whole-plant cannabis-based medicine (CBM) containing delta-9-tetrahydrocannabinol and cannabidiol, taken in conjunction with standard therapies in the control of CINV. METHODS: Patients suffering from CINV despite prophylaxis with standard anti-emetic treatment were randomized to CBM or placebo, during the 120 h post-chemotherapy period, added to standard anti-emetic treatment. Tolerability was measured as the number of withdrawals from the study during the titration period because of adverse events (AEs). The endpoint for the preliminary efficacy analysis was the proportion of patients showing complete or partial response. RESULTS: Seven patients were randomized to CBM and nine to placebo. Only one patient in the CBM arm was withdrawn due to AEs. A higher proportion of patients in the CBM group experienced a complete response during the overall observation period [5/7 (71.4%) with CMB vs. 2/9 (22.2%) with placebo, the difference being 49.2% (95% CI 1%, 75%)], due to the delayed period. The incidence of AEs was higher in the CBM group (86% vs. 67%). No serious AEs were reported. The mean daily dose was 4.8 sprays in both groups. CONCLUSION: Compared with placebo, CBM added to standard antiemetic therapy was well tolerated and provided better protection against delayed CINV. These results should be confirmed in a phase III clinical trial.

Efficacy of psychostimulant drugs for cocaine dependence.

BACKGROUND: Cocaine dependence is an increasingly prevalent disorder for which no medication is approved yet. Likewise opioid for heroin dependence, replacement therapy with psychostimulant could be efficacious for cocaine dependence. OBJECTIVES: To ascertain the efficacy of psychostimulants for cocaine dependence on cocaine use, sustained cocaine abstinence and retention in treatment. The influence of type of drug, comorbid disorders and clinical trial reporting quality over psychostimulants efficacy has also been studied. SEARCH STRATEGY: MEDLINE, EMBASE, PsycINFO, CENTRAL, references of obtained articles and experts in the field. SELECTION CRITERIA: Randomized parallel group controlled clinical trials comparing the efficacy of a psychostimulant against placebo have been included. DATA COLLECTION AND ANALYSIS: Two authors evaluated and extracted data. The Relative Risk (RR) was used to assess dichotomous outcomes except for adverse event (AE) induced dropouts for which the risk difference (RD) was preferred. The Standardized Mean Difference (SMD) was used to assess continuous outcomes. To determine the influence of moderating variables, a stratified analysis was conducted. Funnel plots were drawn to investigate the possibility of publication bias. MAIN RESULTS: Sixteen studies have been included, which have enrolled 1,345 patients. Seven drugs with psychostimulant effect or metabolized to a psychostimulant have been investigated: bupropion, dexamphetamine, methylphenidate, modafinil, mazindol, methamphetamine and selegiline. Psychostimulants did not reduce cocaine use (SMD 0.11, 95%CI: -0.07 to 0.29), showed a statistical trend over improving sustained cocaine abstinence (RR 1.41, 95%CI: 0.98 to 2.02, p=0.07) and did not improve retention in treatment (RR 0.97, 95%CI: 0.89 to 1.05). The proportion of AE induced dropouts was similar for psychostimulants and placebo (RD 0.01, 95%CI: -0.02 to 0.03). When the type of drug was included as a moderating variable, it was shown that the proportion of patients achieving sustained cocaine abstinence was higher with bupropion and dextroamphetamine, and also with modafinil, at a statistical trend of significance, than with placebo. Nevertheless, no studied drug was efficacious on any of the remaining outcomes. Besides, psychostimulants appeared to increase the proportion of patients achieving sustained cocaine and heroin abstinence amongst methadone maintained dual heroin-cocaine addicts. The main findings did not seem to be influenced by clinical trial reporting quality. No evidence of publication bias was found. AUTHORS' CONCLUSIONS: This review found mixed results, therefore evidence of the efficacy of psychostimulants for cocaine dependence is inconclusive. Nevertheless promising results exist for methadone maintained dual heroin-cocaine addicts and for some specific drugs such as dexamphetamine and bupropion.

Efficacy of opiate maintenance therapy and adjunctive interventions for opioid dependence with comorbid cocaine use disorders: A systematic review and meta-analysis of controlled clinical trials.

AIMS: To determine the efficacy of Opiate Maintenance Therapy (OMT) and adjunctive interventions for dual heroin and cocaine dependence by means of a meta-analysis. METHOD: We searched for and retrieved randomized controlled clinical trials. We used RevMan 5.0 with random effects modeling for statistical analysis and for comparisons of relative risk, effect sizes, and confidence intervals. Subsequent moderator variables and sensitivity analyses were performed. RESULTS: Thirty-seven studies, which have enrolled 3,029 patients, have been included in this meta-analysis. High doses of OMT were more efficacious than lower ones in the achievement of sustained heroin abstinence (RR = 2.24 [1.54, 3.24], p < .0001) but had no effect on cocaine abstinence. At equivalent doses, methadone was more efficacious than buprenorphine on cocaine abstinence (RR = 1.63 [1.20, 2.22], p = .002) and also appeared to be superior on heroin abstinence (RR = 1.39 [1.00, 1.93], p = .05). Several pharmacological and psychological potentiation strategies have been investigated. An improvement on sustained cocaine abstinence was achieved with indirect dopaminergic agonists (RR = 1.44 [1.05, 1.98], p = .03) and with contingency management (CM) focusing on cocaine abstinence (RR = 3.11 [1.80, 5.35], p < .0001). CONCLUSIONS: Dual opioid and cocaine dependence can be effectively treated with OMT in combination with adjunctive interventions. Higher OMT doses are preferable to lower ones and methadone to buprenorphine. OMT can be enhanced with indirect dopaminergic drugs and with CM focusing on cocaine abstinence.

[Not Available]. / Utilización de la opinión de los pacientes para la mejora: 5 años de seguimiento (2001-2005).

OBJECTIVE: To evaluate changes in quality over a 5-year period from the perspective of patients, in an attempt to meet their expectations in a new hospital. METHOD: The procedure takes as a reference the results of an opinion survey carried out in the hospital in 2001 and compares these results with those of annual surveys and completes them with information from written complaints and demands for accountability. RESULTS: During the period studied, 821 surveys (a response rate of 22.3%), 3,756 complaints and 105 demands for administrative accountability were received and processed. The surveys revealed a degree of satisfaction of 96%, and study of the changes detected significant differences in comfort and response capacity. The most common reasons for complaints were medical transport (15.3%), delays in receiving care (12.6%), and waiting lists (9.3%). The main reasons for demands for accountability (only 20% of which were accepted) were death or serious secondary outcomes (59%), and the principal causes were related to omissions (42.9%) or malpractice (22.9%). DISCUSSION: Patients' opinions tended to worsen slightly over the 5-year period studied, related to their increased expectations. Although the reasons for making complaints and demands were independent of the problems identified in patients' opinions and showed different dimensions, there were certain areas of overlap. Greater efforts are required in the area of emergency services and, of course, in problems related to comfort, improvement of which is easily achievable and evident with the inauguration of the new hospital.

Efficacy of central nervous system stimulant treatment for cocaine dependence: a systematic review and meta-analysis of randomized controlled clinical trials.

AIMS: To evaluate the efficacy of central nervous system (CNS) stimulants compared with placebo for the treatment of cocaine dependence. METHODS: A systematic review and meta-analysis was carried out. Bibliographic databases were searched, reference lists of retrieved studies were hand-searched and the first authors of each study were contacted. All randomized controlled clinical trials (RCCT) comparing the efficacy of any CNS stimulant with placebo in cocaine-dependent patients were included. Quantitative data synthesis was performed for each single CNS stimulant and for all CNS stimulants. RESULTS: Nine RCCT met the inclusion criteria. These RCCT included 640 patients and compared five CNS stimulants: mazindol, dextroamphetamine, methylphenidate, modafinil and bupropion with placebo. No CNS stimulant improved study retention [RR = 0.94 (0.81-1.09)] or cocaine use [RR = 0.90 (0.79-1.02)]. An exploratory analysis using indirect estimations of cocaine use showed that the proportion of cocaine-positive urine screens was lower with dexamphetamine than with placebo [RR = 0.73 (0.60-0.90)] and that all CNS stimulants pooled together also suggested a significant decrease of cocaine use [RR = 0.87 (0.77-0.99)]. Data on craving could not be meta-analysed due to heterogeneity, but no RCCT found differences in cocaine craving between active drug and placebo except one, whose outcome favoured dexamphetamine. No serious adverse event (AE) was reported. Average of AE-induced dropouts was low and was greater for CNS stimulants than placebo: 4.4% versus 1.3% (P = 0.03). CONCLUSION: The main outcomes of this study do not support the use of CNS stimulants for cocaine dependence. Nevertheless, secondary analyses provide some hopeful results that encourage further research with these drugs, mainly with dexamphetamine and modafinil.

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.