Indications related to antidepressant prescribing in the Nivel-PCD database and the SIDIAP database.

BACKGROUND: Antidepressant drug consumption has increased, mainly in the elderly. This trend could be explained by the use for indications other than depression. We aimed to describe the indications related to antidepressant drug new users in two primary care settings. METHODS: A longitudinal study of new antidepressant users aged ≥65 was conducted, with data from the Nivel-PCD (The Netherlands) and SIDIAP (Catalonia) databases (2010-2015). As a proxy for indication, diagnoses registered around the 3 months of antidepressant prescribing were collected. Indications were classified in seven categories and an additional one of non-selected indications. The percentage and incidence calculated over the total population registered was described. RESULTS: A total of 16,537 and 199,168 new antidepressant users were identified in the Nivel-PCD and SIDIAP databases, respectively (women aged 65-69 were the most prevalent). Depression was the most frequent indication (24.0% and 31.3%), followed by anxiety (12.5% and 19.5%) and sleep disorders (10.2% and 26.4%). Tricyclic antidepressants were the most commonly prescribed in Nivel-PCD (48.7%), mainly associated with neuropathic pain, and selective serotonin reuptake inhibitor antidepressants in SIDIAP (63.1%), associated with depression. The non-selected indications category showed an upward trend in the Nivel-PCD database while in the SIDIAP database it decreased. LIMITATIONS: It is not mandatory for physicians to register a diagnosis with each prescription. CONCLUSIONS: Depression was the most common prescribing indication in The Netherlands and Spain, followed by anxiety and sleep disorders. The most commonly prescribed antidepressant differed between the countries and is likely explained by differences in local guidelines.

Adherence to Direct Oral Anticoagulants in Patients With Non-Valvular Atrial Fibrillation: A Cross-National Comparison in Six European Countries (2008-2015).

Aims: To describe and compare the adherence to different direct oral anticoagulants (DOACs) in eight European databases representing six countries. Methods: Longitudinal drug utilization study of new users (≥18 years) of DOACs (dabigatran, rivaroxaban, apixaban) with a diagnosis of non-valvular atrial fibrillation (2008-2015). Adherence was examined by estimating persistence, switching, and discontinuation rates at 12 months. Primary non-adherence was estimated in BIFAP and SIDIAP databases. Results: The highest persistence rate was seen for apixaban in the CPRD database (81%) and the lowest for dabigatran in the Mondriaan database (22%). The switching rate for all DOACs ranged from 2.4 to 13.1% (Mondriaan and EGB databases, respectively). Dabigatran had the highest switching rate from 5.0 to 20.0% (Mondriaan and EGB databases, respectively). The discontinuation rate for all DOACs ranged from 16.0 to 63.9% (CPRD and Bavarian CD databases, respectively). Dabigatran had the highest rate of discontinuers, except in the Bavarian CD and AOK NORDWEST databases, ranging from 23.2 to 64.6% (CPRD and Mondriaan databases, respectively). Combined primary non-adherence for examined DOACs was 11.1% in BIFAP and 14.0% in SIDIAP. There were differences in population coverage and in the type of drug data source among the databases. Conclusion: Despite the differences in the characteristics of the databases and in demographic and baseline characteristics of the included population that could explain some of the observed discrepancies, we can observe a similar pattern throughout the databases. Apixaban was the DOAC with the highest persistence. Dabigatran had the highest proportion of discontinuers and switchers at 12 months in most databases (EMA/2015/27/PH).

Study of antidepressant use in 5 European settings. Could economic, sociodemographic and cultural determinants be related to their use?

BACKGROUND: We aimed at describing the trends in antidepressants use (AD) by age and sex, during 2007-2011, in 5 European settings (Sweden, Norway, Denmark, Catalonia and Veneto), and to assess whether the differences found across settings could be related to economic, social and cultural determinants. METHODS: We collected data of AD use expressed in defined daily doses (DDD). Data were retrieved from population-based databases. We calculated DDD/1000 inhabitants/day. We analysed which economic, social, and cultural covariates determined between-settings differences in AD consumption. RESULTS: The use of AD showed an increasing trend during the study period, being Selective Serotonin Reuptake Inhibitors the most consumed, followed "others AD". Women and the elderly showed the highest AD consumption. Between-settings variability in AD consumption showed a positive correlation with pharmaceutical expenditure and a negative one with general practitioner's rate. After adjusting by pharmaceutical expenditure and general practitioners rate Masculinity, Long-Term Orientation and Individualism cultural dimensions were associated with AD use by using the Hofstede´s cultural dimensions model. LIMITATIONS: This study has been conducted in administrative databases, with no information on AD use by indication; differences among AD use could be related to their prescription for other disorders. Analyses were based on a small dataset and none of the results reached statistical significance. CONCLUSIONS: AD use increased through 2007-2011. Pharmaceutical expenditure and General Practitioners rate, Masculinity, Long-Term Orientation and Individualism explained the differences in AD use between countries. People's attitude should be considered when designing national campaigns to improve antidepressant use.

Exposure to medicines among patients admitted for hip fracture and the case-fatality rate at 1 year: a longitudinal study.

PURPOSE: To describe the demographic and clinical characteristics and the pre-fracture exposure to medicines of patients admitted for a hip fracture, and to explore their association with fatal outcome 1 year after the fracture. METHODS: All patients ≥ 65 years old admitted for a hip fracture in a tertiary hospital in Barcelona between January 1 and December 31 2007 were included. Data on the patients' clinical characteristics before and during hospital admission and on pre-fracture exposures to medicines were collected from the clinical records. One-year mortality was checked by approaching the patients and their families and was cross-checked with the national mortality statistics database. A Cox proportional hazards analysis was carried out. RESULTS: Four hundred and fifty-six patients [mean age (SD) 82.9 (7.2) years, 73.5 % female], were admitted with hip fracture during the study period. Almost 80 % of the patients (363, 79.6 %) had three or more associated conditions, and 41.7 % received pre-fracture treatment with five or more drugs. The case-fatality rate during hospital admission was 4.6 % (21 patients). One hundred and seven patients died within 1 year (23.5 %). Advanced age, male gender, two or more associated chronic conditions, cancer, severe cognitive impairment, and treatment with opiates before fracture were significantly associated with the risk of dying. An inverse association was recorded between mortality and pre-hospital exposure to medicines for osteoporosis. CONCLUSIONS: One-quarter of patients admitted for hip fracture died within 1 year after the fracture. Exposure to opiates before hip fracture was associated with an increased 1-year death rate, whereas treatment with drugs for osteoporosis was associated with a decrease in death rate. These results should be confirmed in studies with detailed prospective collection of information on exposure to medicines.

Acute exercise increases plasma total antioxidant status and antioxidant enzyme activities in untrained men.

Antioxidant defences are essential for cellular redox regulation. Since free-radical production may be enhanced by physical activity, herein, we evaluated the effect of acute exercise on total antioxidant status (TAS) and the plasma activities of catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase and its possible relation to oxidative stress resulting from exercise. Healthy untrained male subjects (n = 34) performed three cycloergometric tests, including maximal and submaximal episodes. Venous blood samples were collected before and immediately after each different exercise. TAS and enzyme activities were assessed by spectrophotometry. An increase of the antioxidant enzyme activities in plasma was detected after both maximal and submaximal exercise periods. Moreover, under our experimental conditions, exercise also led to an augmentation of TAS levels. These findings are consistent with the idea that acute exercise may play a beneficial role because of its ability to increase antioxidant defense mechanisms through a redox sensitive pathway.

Melatonin reduces membrane rigidity and oxidative damage in the brain of SAMP8 mice.

We evaluated the autophagy-lysosomal pathway and membrane fluidity in brain cells and mitochondrial membranes obtained from senescence-accelerated (SAMP(8)) and senescence-resistant (SAMR(1)) mice at 5 and 10 months of age. Moreover, we studied whether chronic treatment from age 1 to 10 months with melatonin stabilizes membrane fluidity. Fluidity was measured by polarization changes of 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene-p-toluene sulfonate. Results showed that in untreated animals at 5 months of age, synaptosomal and mitochondrial fluidity was decreased in SAMP(8) compared to SAMR(1), as was the cathepsin D/B ratio, indicating dysfunction of the autophagy-lysosomal pathway. Moreover, we detected synaptosomal rigidity and programmed cell death capability in both groups at 10 months of age. Mitochondrial fluidity, however, did not show a significant age-dependent change but was lower in SAMP(8) than in SAMR(1) at the 5- and 10-month time points. Melatonin administration prevented rigidity in the mitochondrial membrane and seemed to decrease age-related autophagy-lysosomal alterations. These data suggest that melatonin may act to slow down the aging process because of its ability to enhance membrane fluidity and maintain structural pathways.

Erythrocyte membrane fluidity and indices of plasmatic oxidative damage after acute physical exercise in humans.

Optimal levels of membrane fluidity are essential for numerous cell functions including cell growth, solute transport and signal transduction. Since exercise enhances free radical production, our aim was to evaluate in healthy male subjects the effects of an acute bout of maximal and submaximal exercise on the erythrocyte membrane fluidity and its possible relation to the oxidative damage overproduction due to exercise. Subjects (n = 34) performed three cycloergometric tests: a continuous progressive exercise, a strenuous exercise until exhaustion and an acute bout of exercise at an intensity corresponding to 70% of maximal work capacity for 30 min. Venous blood samples were collected before and immediately after these exercises. Erythrocyte membrane fluidity was assessed by fluorescence spectroscopy. Plasma malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) concentrations and carbonyl content of plasmatic proteins were used as an index of lipid and protein oxidation, respectively. Exercise produced a dramatic drop in the erythrocyte membrane fluidity as compared to resting time, but this was not accompanied by significant changes in the plasmatic MDA and 4-HDA concentrations. The highest erythrocyte membrane rigidity was detected immediately after strenuous exercise until exhaustion was performed. Protein carbonyl levels were higher after exhaustive exercises than at rest. Continuous progressive and strenuous exercises until exhaustion, but not submaximal workload, resulted in a significant enhanced accumulation of carbonylated proteins in the plasma. These findings are consistent with the idea that exercise exaggerates oxidative damage, which may contribute, at least partially, to explain the rigidity in the membrane of the erythrocytes due to acute exercise.

In vivo hepatic oxidative stress because of carbon tetrachloride toxicity: protection by melatonin and pinoline.

The protective in vivo effects of melatonin or pinoline on carbon tetrachloride (CCl(4))-induced oxidative damage were investigated in liver of rats and compared to rats injected only with CCl(4) (5 mL/kg body weight). Hepatic cell membrane fluidity, monitored using fluorescence spectroscopy, exhibited a significant decrease in animals exposed to CCl(4) compared to control rats. Increases in lipid and protein oxidation, as assessed by concentrations of malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA), and protein carbonylation, respectively, were also seen in hepatic homogenates of animals exposed to CCl(4). The administration of melatonin (10 mg/kg body weight) or pinoline injected 30 min before and 1 hr after CCl(4), fully prevented membrane rigidity and protein oxidation. However, treatment with melatonin was more effective in terms of reducing lipid peroxidation than pinoline, as the increases in MDA+4-HDA levels because of CCl(4) were reduced by 93.4% and 34.4% for melatonin or pinoline, respectively. Livers from CCl(4)-injected rats showed several histopathological alterations; above all, there were signs of necrosis and ballooning degeneration. The concurrent administration of melatonin or pinoline reduced the severity of these morphological changes. On the basis of the biochemical and histopathological findings, we conclude that both melatonin and pinoline were highly effective in protecting the liver against oxidative damage and membrane rigidity because of CCl(4). Therefore, these indoles may be useful as cotreatments for patients with hepatic intoxication induced by CCl(4).

Efecto protector de 5-metoxi-indolaminas pineales en la oxidación de sinaptosomas mediada por radicales libres / No disponible

No disponible

Estudio de la repercusión del estrés oxidativo sobre la fluidez de membrana en un modelo animal de la esclerosis lateral amiotrófica / No disponible

No disponible

Peorxidación lipídica en pacientes afectos de tumores del sistema nervioso central / No disponible

No disponible

Efecto protector de la melatonina frente a la toxicidad de la mitomicina C / No disponible

No disponible

Effects of tryptophan and 5-hydroxytryptophan on the hepatic cell membrane rigidity due to oxidative stress.

The ability of several indoleamines to scavenge free radicals is well documented. Our aim was to evaluate the ability of 0.01-3 mM tryptophan (Trp) and 0.1-5 mM 5-hydroxytryptophan (5-OH-Trp) to protect hepatic cell membranes against 0.1 mM FeCl(3) plus 0.1 mM ascorbic acid-induced lipid peroxidation and increases in membrane rigidity. Membrane fluidity was evaluated using fluorescence spectroscopy. Lipid and protein oxidation were estimated by quantifying malondialdehyde (MDA) plus 4-hydroxyalkenals (4-HDA) concentrations and carbonyl group content, respectively. Exposure to FeCl(3) plus ascorbic acid increased hepatic cell membrane rigidity, MDA + 4-HDA and carbonyl content. The presence of 5-OH-Trp, but not Trp, attenuated these changes. In the absence of oxidative stress, neither indoleamine modified fluidity, MDA + 4-HDA or carbonylation. These results suggest that C5 hydroxylation determines the ability of Trp to preserve membrane fluidity in the presence of oxidative stress.

Protective effect of melatonin against mitomycin C-induced genotoxic damage in peripheral blood of rats.

Mitomycin C (MMC) generates free radicals when metabolized. We investigated the effect of melatonin against MMC-induced genotoxicity in polychromatic erythrocytes and MMC-induced lipid peroxidation in brain and liver homogenates. Rats (N = 36) were classified into 4 groups: control, melatonin, MMC, and MMC + melatonin. Melatonin and MMC doses of 10 mg/kg and 2 mg/kg, respectively, were injected intraperitoneally. Peripheral blood samples were collected at 0, 24, 48, 72, and 96 hours posttreatment and homogenates were obtained at 96 hours posttreatment. The number of micronucleated polychromatic erythrocytes (MN-PCE) per 1000 PCE was used as a genotoxic marker. Malondialdehyde (MDA) plus 4-hydroxyalkenal (4-HDA) levels were used as an index of lipid peroxidation. The MMC group showed a significant increase in MN-PCE at 24, 48, 72, and 96 hours that was significantly reduced with melatonin begin coadministrated. No significant differences were found in lipid peroxidation. Our results indicate that MMC-induced genotoxicity can be reduced by melatonin.

Use of granulocyte colony-stimulating factor (G-CSF) and outcome in patients with non-chemotherapy agranulocytosis.

PURPOSE: The use of granulocyte colony-stimulating factor (G-CSF) in the treatment of non-chemotherapy drug- induced agranulocytosis is controversial. We aimed at assessing the effect of G-CSF on the duration of agranulocytosis. METHODS: To assess the effect of G-CSF on the duration of agranulocytosis, a Cox proportional hazard model with an estimated propensity score covariate adjusting for several prognostic factors was used. RESULTS: One hundred and forty-five episodes of agranulocytosis were prospectively collected from January 1994 to December 2000 in Barcelona (Spain). No differences were found in the case-fatality rate between treated (9 of 101, 8.9%) and not treated (5 of 44, 11.4%) patients. The median time to reach a neutrophil count > or =1.0 x 10(9)/L was 5 days (95%CI 5-6) in patients treated with G-CSF compared to 7 days (95%CI 6-8) in those not treated, with a hazard ratio of 1.58 (95% CI 1.1-2.3). CONCLUSIONS: G-CSF shortens time to recovery in patients with agranulocytosis. However, as an effect on case-fatality has not been recorded, and data on cost-effectiveness are lacking, it would be wise to restrict its use to high-risk patients.

Protective effect of melatonin and pinoline on nitric oxide-induced lipid and protein peroxidation in rat brain homogenates.

Nitric oxide (NO) is a physiological neurotransmitter, a mediator of the excitatory neurotransmitter glutamate pathways that regulates several neuroendocrine functions, but excessive NO is toxic by itself and it interacts with superoxide radical (O(2)(-)) to form the peroxynitrite anion (ONOO(-)). Using rat brain homogenates, we investigated the effects of melatonin and pinoline in preventing the level of lipid peroxidation (LPO) and carbonyl contents in proteins induced by nitric oxide (NO) which was released by the addition of sodium nitroprusside (SNP). Lipid and protein peroxidation were estimated by quantifying malondialdehyde (MDA) and 4-hydroxyalkenal (4-HDA) concentrations and carbonyl contents, respectively. SNP increased MDA+4-HDA and carbonyl contents production in brain homogenates in a time and concentration dependent manner. Both, melatonin and pinoline reduced NO-induced LPO and carbonyl contents in a dose-dependent manner in concentrations from 0.03 to 3 mM and 1 to 300 microM, respectively. Under the in vitro conditions of this experiment, both antioxidants were more efficient in limiting SNP protein oxidation than lipid damage.

[Randomised clinical trial to evaluate the efficacy of a multi-factorial intervention to reduce hospitalisation and improve the quality of life of patients with heart failure]. / Ensayo clínico aleatorizado para evaluar la eficacia de una intervención multifactorial para reducir las hospitalizaciones y mejorar la calidad de vida de los pacientes con insuficiencia cardíaca.

OBJECTIVES: To evaluate the efficacy of a multi-disciplinary non-pharmacological intervention to reduce cardiovascular mortality and hospital re-admissions due to heart failure. DESIGN: Randomised, open, controlled, parallel, multi-centre prospective clinical trial. SETTING: Sardenya Primary Care Centre (PCC), les Corts PCC, "El Remei" PCC (Vic Sud), Vall d'Hebron Hospital, Hospital Clínic, Vic Hospital, Hospital Dos de Maig. PARTICIPANTS: 300 patients diagnosed with heart failure. INTERVENTION: Monthly home visits with intercalated phone calls from very well trained nursing staff to provide education on the illness and treatments, optimise therapy compliance, and inform on self-monitoring and management (especially early detection and treatment of decompensation). MAIN MEASUREMENTS: Combined variable of mortality for cardiovascular reasons and re-hospitalisation due to heart failure (via Casualty and/or Admissions) at 1 year. Health-related quality of life. DISCUSSION: Open study, as it is impossible to mask the intervention. The home intervention is not too complex and is easily performed by well-trained health professionals. Its use could be generalised, if a clinically relevant degree of efficacy was shown.

Effects of trace elements on membrane fluidity.

According to the Fluid Mosaic Model, a biological membrane is a two-dimensional fluid of oriented proteins and lipids. The lipid bilayer is the basic structure of all cell and organelle membranes. Cell membranes are dynamic, fluid structures, and most of their molecules are able to move in the plane of the membrane. Fluidity is the quality of ease of movement and represents the reciprocal value of membrane viscosity. Fluid properties of biological membranes are essential for numerous cell functions. Even slight changes in membrane fluidity may cause aberrant function and pathological processes. Several evidences suggest that trace elements, e.g., iron, copper, zinc, selenium, chromium, cadmium, mercury and lead may influence membrane fluidity. The interaction of heavy metals with cellular membranes may contribute to explain, at least partially, the toxicity associated with these metals.

Ensayo clínico aleatorizado para evaluar la eficacia de una intervención multifactorial para reducir las hospitalizaciones y mejorar la calidad de vida de los pacientes con insuficiencia cardíaca / Randomised clinical trial to evaluate the efficacy of a multi-factorial intervention to reduce hospitalisation and improve the quality of life of patients with heart failure

Objetivos. Evaluar la eficacia de una intervención multidisciplinaria no farmacológica para reducir la mortalidad cardiovascular y los reingresos hospitalarios por insuficiencia cardíaca. Diseño. Ensayo clínico prospectivo, aleatorizado, abierto, controlado, paralelo y multicéntrico. Emplazamiento. Centros de atención primaria Sardenya, Les Corts y Vic Sud «El Remei», y hospitales Vall d'Hebron, Clínic, Vic y Dos de Maig. Participantes. Participarán 300 pacientes con el diagnóstico de insuficiencia cardíaca. Intervención. Visitas domiciliarias mensuales con llamadas telefónicas intercaladas por personal de enfermería muy bien entrenado donde se proporcionará educación sobre la enfermedad y los tratamientos, optimización del cumplimiento terapéutico, educación sobre el autocontrol y el manejo (particularmente detección precoz y tratamiento de las descompensaciones). Mediciones principales. Variable combinada de mortalidad por causa cardiovascular y rehospitalizaciones por insuficiencia cardíaca (urgencias y/o ingresos) al cabo de 1 año. Calidad de vida relacionada con la salud. Discusión. Estudio de carácter abierto, ya que no es posible enmascarar la intervención. La intervención domiciliaria no es excesivamente compleja y puede ser realizada con facilidad por profesionales sanitarios bien entrenados; se podría generalizar su aplicación si se demostrara un grado de eficacia clínicamente relevante

Objectives. To evaluate the efficacy of a multi-disciplinary non-pharmacological intervention to reduce cardiovascular mortality and hospital re-admissions due to heart failure. ;;Design. Randomised, open, controlled, parallel, multi-centre prospective clinical trial. ;;Setting. Sardenya Primary Care Centre (PCC), les Corts PCC, "El Remei" PCC (Vic Sud), Vall d'Hebron Hospital, Hospital Clínic, Vic Hospital, Hospital Dos de Maig. ;;Participants. 300 patients diagnosed with heart failure. ;;Intervention. Monthly home visits with intercalated phone calls from very well trained nursing staff to provide education on the illness and treatments, optimise therapy compliance, and inform on self-monitoring and management (especially early detection and treatment of decompensation). ;;Main measurements. Combined variable of mortality for cardiovascular reasons and re-hospitalisation due to heart failure (via Casualty and/or Admissions) at 1 year. Health-related quality of life. ;;Discussion. Open study, as it is impossible to mask the intervention. The home intervention is not too complex and is easily performed by well-trained health

Melatonin improves deferoxamine antioxidant activity in protecting against lipid peroxidation caused by hydrogen peroxide in rat brain homogenates.

Deferoxamine (DF) is an antioxidant molecule because of its ability to chelate iron. This study compared the ability of DF alone or in combination with melatonin, 5-methoxytryptophol or pinoline in preventing lipid peroxidation due to hydrogen peroxide (H(2)O(2)) in rat brain homogenates. Malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) in the homogenates were measured as indices of lipid peroxidation. Incubation of homogenates with DF reduced, in a dose-dependent manner, MDA+4-HDA formation due to H(2)O(2). When melatonin, 5-methoxytryptophol or pinoline were added to the incubation medium, the efficacy of DF in preventing lipid peroxidation was enhanced. These cooperative effects between DF, melatonin, and related pineal products may be important in protecting tissues from the oxidative stress due to iron overload.