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In the present study, the safety, tolerance and impact of 1×109 cfu Bacillus clausii CSI08, 1×109 cfu Bacillus megaterium MIT411 and a probiotic cocktail containing Bacillus subtilis DE111®, Bacillus megaterium MIT411, Bacillus coagulans CGI314, and Bacillus clausii CSI08 with a total count of 2.0×109 cfu administered daily were assessed as compared with a maltodextrin containing placebo control. A total of 98 study participants received daily doses for 45 days, followed by a washout period of 2 weeks. A questionnaire to capture the incidence and duration of upper respiratory tract, urinary tract and/or gastrointestinal complaints and a diary to capture stool regularity and consistency was kept daily to record compliance throughout the 45 days. Faecal and blood samples were collected for microbiological and haematological analysis at the start and end of the treatment period. The probiotic cocktail significantly decreased the incidence of loose stools throughout the entire study. The recorded respiratory, urinary and gastrointestinal symptoms, defecation frequency and other stool consistency were not influenced. No clinically relevant changes in blood parameters, such as liver and kidney function and no serious adverse events appeared during and after administration. There were no changes in symptoms including sadness, irritability, energy, appetite, tension, stress, sleep, cardiovascular events, aches and pains, and dizziness as determined by a mood questionnaire administered to participants at baseline and at the end of the treatment period. Similarly, the measured inflammatory cytokines, antioxidant levels, cholesterol, triglycerides, free amino acids or minerals remained unaffected. There were no negative changes in alpha or beta diversity of the microbiota with any of the treatment groups. These promising data suggest that these treatments were safe and well tolerated, and further work with larger cohorts are justified to determine the efficacy of these potential probiotics in select demographic groups. Trial registration number with clinicaltrials.gov at NCT04758845.
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Bacillus clausii , Bacillus megaterium , Probióticos , Humanos , Proyectos Piloto , Resultado del Tratamiento , Método Doble Ciego , DolorRESUMEN
Previous studies using ileostomy samples from study participants demonstrated that the spore-forming probiotic Bacillus subtilis DE111® can germinate in the small intestine as early as 4 hours after ingestion. Metabolomics, proteomics and sequencing technologies, enabled further analysis of these samples for the presence of hypoglycaemic, hypolipidemic, antioxidant, anti-inflammatory and antihypertensive molecules. In the DE111 treatment group, the polyphenols trigonelline and 2,5-dihydroxybenzoic acid, orotic acid, the non-essential amino acid cystine and the lipokine 12,13-diHome were increased. DE111 also reduced acetylcholine levels in the ileostomy samples, and increased the expression of leucocyte recruiting proteins, antimicrobial peptides and intestinal alkaline phosphatases of the brush border in the small intestine. The combination of B. subtilis DE111 and the diet administered during the study increased the expression of the proteins phosphodiesterase ENPP7, ceramidase ASAH2 and the adipokine Zn-alpha-2-glycoprotein that are involved in fatty acid and lipid metabolism. Acute B. subtilis DE111 ingestion had limited detectable effect on the microbiome, with the main change being its increased presence. These findings support previous data suggesting a beneficial role of DE111 in digestion, metabolism, and immune health that appears to begin within hours of consumption.
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Bacillus subtilis , Probióticos , Humanos , Bacillus subtilis/fisiología , Intestino Delgado , Antioxidantes/metabolismo , Ingestión de AlimentosRESUMEN
BACKGROUND: Catalonia requires decentralized and simplified strategies for the diagnosis of viremic HCV infection among people who inject drugs (PWID). We aimed to perform a direct comparison of the diagnostic performance between two, single-step strategies for the screening and diagnosis of viremic HCV infection in PWID attending a drug consumption room (DCR) in Barcelona: i) on-site HCV-RNA testing using the point-of-care test (PoCT) Xpert HCV VL Fingerstick; and ii) on-site dried blood spots (DBS) collection for HCV-RNA testing at the laboratory (in-house assay). Additionally, we aimed to assess participants' preferences in receiving HCV-RNA testing results and feasibility of same-day delivery of PoCT results. METHODS: The real-world, clinical performance of these two strategies was established in comparison with the reference method (HCV viral load testing with the Xpert HCV Viral Load assay at the laboratory from venous plasma collected at the DCR). HCV genotypes/subtypes and HIV status were also determined by sequencing and serology, respectively. A questionnaire including preferences regarding the delivery of test results was administered. RESULTS: The prevalence of HCV-RNA was 63.0% (of which 25.8% were co-infected with HIV). The RNA-PoCT showed a sensitivity of 98.4% for detectable viral loads (>4 IU/mL) and of 100% for quantifiable viral loads (≥10, ≥1000 and ≥3000 IU/mL). For the DBS-based assay, a sensitivity of 93.7% was obtained for detectable viral loads, 96.7% for the quantifiable ≥10 IU/mL threshold, and 98.3% for both the quantifiable ≥1000 and ≥3000 IU/mL thresholds. No significant differences were detected between the sensitivity values of these two strategies, and the specificity was 100% in both cases. Half of the participants preferred to receive the HCV-RNA result on the same day, and 80% of participants received their RNA-PoCT results on the same day. CONCLUSIONS: Both the HCV-RNA PoCT and the DBS-based assay are highly reliable tools for the simplified diagnosis of viremic HCV infection among current PWID. These strategies allow for on-site sample collection and delivery of test results, facilitating decentralized care in harm reduction services.
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Hepatitis C , Preparaciones Farmacéuticas , Pruebas con Sangre Seca , Hepacivirus/genética , Hepatitis C/diagnóstico , Hepatitis C/epidemiología , Humanos , Sistemas de Atención de Punto , ARN Viral , Sensibilidad y Especificidad , España/epidemiologíaRESUMEN
INTRODUCTION AND OBJECTIVE: The ODHIN trial found that training and support and financial reimbursement increased the proportion of patients that were screened and given advice for their heavy drinking in primary health care. However, the impact of these strategies on professional accuracy in delivering screening and brief advice is underresearched and is the focus of this paper. METHOD: From 120 primary health care units (24 in each jurisdiction: Catalonia, England, the Netherlands, Poland, and Sweden), 746 providers participated in the baseline and the 12-week implementation periods. Accuracy was measured in 2 ways: correctness in completing and scoring the screening instrument, AUDIT-C; the proportion of screen-negative patients given advice, and the proportion of screen-positive patients not given advice. Odds ratios of accuracy were calculated for type of profession and for intervention group: training and support, financial reimbursement, and internet-based counselling. RESULTS: Thirty-two of 36 711 questionnaires were incorrectly completed, and 65 of 29 641 screen-negative patients were falsely classified. At baseline, 27% of screen-negative patients were given advice, and 22.5% screen-positive patients were not given advice. These proportions halved during the 12-week implementation period, unaffected by training. Financial reimbursement reduced the proportion of screen-positive patients not given advice (OR = 0.56; 95% CI, 0.31-0.99; P < .05). CONCLUSION: Although the use of AUDIT-C as a screening tool was accurate, a considerable proportion of risky drinkers did not receive advice, which was reduced with financial incentives.
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Alcoholismo/diagnóstico , Alcoholismo/terapia , Tamizaje Masivo/organización & administración , Atención Primaria de Salud/organización & administración , Errores Diagnósticos/estadística & datos numéricos , Femenino , Humanos , Masculino , Tamizaje Masivo/economía , Tamizaje Masivo/normas , Motivación , Atención Primaria de Salud/economía , Atención Primaria de Salud/normasRESUMEN
BACKGROUND: Screening and brief interventions (SBI) in primary healthcare are cost-effective in risky drinkers, yet they are not offered to all eligible patients. This qualitative study aimed to provide more insight into the factors and mechanisms of why, how, for whom and under what circumstances implementation strategies work or do not work in increasing SBI. METHODS: Semi-structured interviews were conducted between February and July 2014 with 40 GPs and 28 nurses in Catalonia, the Netherlands, Poland, and Sweden. Participants were purposefully selected from the European Optimising Delivery of Healthcare Interventions (ODHIN) trial. This randomised controlled trial evaluated the influence of training and support, financial reimbursement and an internet-based method of delivering advice on SBI. Amongst them were 38 providers with a high screening performance and 30 with a low screening performance from different allocation groups. Realist evaluation was combined with the Tailored Implementation for Chronic Diseases framework for identification of implementation determinants to guide the interviews and analysis. Transcripts were analysed thematically with the diagram affinity method. RESULTS: Training and support motivated SBI by improved knowledge, skills and prioritisation. Continuous provision, sufficient time to learn intervention techniques and to tailor to individual experienced barriers, seemed important T&S conditions. Catalan and Polish professionals perceived financial reimbursement to be an additional stimulating factor as well, as effects on SBI were smoothened by personnel levels and salary levels. Structural payment for preventive services rather than a temporary project based payment, might have increased the effects of financial reimbursement. Implementing e-BI seem to require more guidance than was delivered in ODHIN. Despite the allocation, important preconditions for SBI routine seemed frequent exposure of this topic in media and guidelines, SBI facilitating information systems, and having SBI in protocol-led care. Hence, the second order analysis revealed that the applied implementation strategies have high potential on the micro professional level and meso-organisational level, however due to influences from the macro- level such as societal and political culture the effects risks to get nullified. CONCLUSIONS: Essential determinants perceived for the implementation of SBI routines were identified, in particular for training and support and financial reimbursement. However, focusing only on the primary healthcare setting seems insufficient and a more integrated SBI culture, together with meso- and macro-focused implementation process is requested. TRIAL REGISTRATION: ClinicalTrials.gov. Trial identifier: NCT01501552 .
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Trastornos Relacionados con Alcohol/diagnóstico , Trastornos Relacionados con Alcohol/terapia , Medicina General/métodos , Entrevista Motivacional , Atención Primaria de Salud/métodos , Desarrollo de Programa/métodos , Adulto , Consumo de Bebidas Alcohólicas/terapia , Actitud del Personal de Salud , Diagnóstico Precoz , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Investigación Cualitativa , Asunción de Riesgos , AutoeficaciaRESUMEN
BACKGROUND: Cannabis use and misuse have become a public health problem. There is a need for reliable screening and assessment tools to identify harmful cannabis use at an early stage. We conducted a systematic review of published instruments used to screen and assess cannabis use disorders. METHOD: We included papers published until January 2013 from seven different databases, following the PRISMA guidelines and a predetermined set of criteria for article selection. Only tools including a quantification of cannabis use and/or a measurement of the severity of dependence were considered. RESULTS: We identified 34 studies, of which 25 included instruments that met our inclusion criteria: 10 scales to assess cannabis use disorders, seven structured interviews, and eight tools to quantify cannabis use. Both cannabis and substance use scales showed good reliability and were validated in specific populations. Structured interviews were also reliable and showed good validity parameters. Common limitations were inadequate time-frames for screening, lack of brevity, undemonstrated validity for some populations (e.g., psychiatric patients, female gender, adolescents), and lack of relevant information that would enable routine use (e.g., risky use, regular users). Instruments to quantify consumption did not measure grams of the psychoactive compounds, which hampered comparability among different countries or regions where tetrahydrocannabinol concentrations may differ. CONCLUSIONS: Current instruments available for assessing cannabis use disorders need to be further improved. A standard cannabis unit should be studied and existing instruments should be adapted to this standard unit in order to improve cannabis use assessment.
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Abuso de Marihuana/diagnóstico , Escalas de Valoración Psiquiátrica/normas , Psicometría/instrumentación , Encuestas y Cuestionarios/normas , HumanosRESUMEN
The constitutional precautionary principle as applied in laws governing health care at the community level requires rigorous scientific assessment. The goal of this assessment is to provide authorities with sound evidence as a basis for implementing precautionary measures in function of degree of risk and other parameters such as the level of public health protection that is high in the EU. As the political authority, the government can act independently of conclusions issued by scientific commissions provided that the commission's level of expertise meets national and European standards and that research methodology and findings are consistent with scientific data published in the international literature. These requirements were not meet for the chikungunya pandemic that struck France on Reunion Island and Mayotte from 2004 to 2006. This epidemic that was preceded by many outbreaks in Indonesia between 2001 and 2003 began in Africa and then swept across the Indian Ocean to India and Asia. After an overview of the scientific assessment, this article raises arguments supporting possible allegations of gross misgovernance by the state and experts.
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Infecciones por Alphavirus/epidemiología , Infecciones por Alphavirus/terapia , Medicina de Emergencia Basada en la Evidencia , Directrices para la Planificación en Salud , Proyectos de Investigación , Infecciones por Alphavirus/transmisión , Fiebre Chikungunya , Comoras/epidemiología , Epidemias , Medicina de Emergencia Basada en la Evidencia/métodos , Medicina de Emergencia Basada en la Evidencia/normas , Gobierno , Humanos , Reunión/epidemiología , Factores de TiempoAsunto(s)
Anafilaxia/complicaciones , Vasos Coronarios/anatomía & histología , Infarto del Miocardio/etiología , Combinación Amoxicilina-Clavulanato de Potasio/efectos adversos , Combinación Amoxicilina-Clavulanato de Potasio/inmunología , Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Anafilaxia/etiología , Anafilaxia/inmunología , Electrocardiografía , Femenino , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Persona de Mediana Edad , Infarto del Miocardio/fisiopatología , Sinusitis/tratamiento farmacológicoRESUMEN
OBJECTIVE: To describe the process performed in Catalonia (Spain) to design an information system for monitoring new cases of HIV infection. METHODS: A survey was used to evaluate perception of the need for notification of HIV infection by health care professionals (n = 106), as well as their opinions of the various possibilities for the implementation of the notification system. As a result of this evaluation, a specific technical report defining the objectives and technical characteristics of the new notification system was produced. The feasibility of the system in health centres was evaluated through discussions with health care professionals, health authorities and Non-Governmental Organizations, and a second survey was designed to evaluate the use of a personal identification code (PIC) from the individual health card (IHC). This process took plabe between 1998 and 2000. RESULTS: A total of 84.5% of the health care professionals believed that HIV notification should be mandatory and confidential; 90.4%, were of the opinion that notification would enable identification of the epidemiological characteristics of infected individualos, and 75% believed that these individuals would have to be identified by name. Finally, 66% of the health care professionals believed that the use of the PIC from the IHC would be feasible as the personal identifier in HIV notification. A final proposal was draw up and 1 January, 2001 was set as the date to initiate the pilot phase of the new HIV notification system. CONCLUSIONS: Most of the health care professionals surveyed expressed the need for notification of HIV infection, and for such notification to receive institutional endorsement. They also believed that, as with other diseases of individualized mandatory reporting, notification should be carried out with a single personal identifier. The information obtained from notification of HIV infection is essential for the optimal planning of preventive programs and the provision of health services. The main difficulties observed were that HIV infection has not been included among the diseases of mandatory reporting, as well as the low implantation of the PIC in the hospitals' clinical registries. All the sectors involved have an important role to play in creating the conditions necessary for the notification system of new cases of HIV infection to be feasible and useful.
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Consenso , Notificación de Enfermedades , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Estudios de Factibilidad , Femenino , Humanos , Masculino , Proyectos Piloto , España , Encuestas y CuestionariosRESUMEN
The XOAZRP TCF sequence was applied to bleach wheat straw pulp. Following each bleaching stage, the properties of the pulp (viz. kappa number, standard viscosity, borohydride viscosity and brightness) and of the resulting effluents were determined. The performance of the reagents was analyzed through the studies of xylanase treatment and crystallinity and scanning electron microscopy of the pulps. Finally, the pulp was refined at 1000 revolutions in a PFI mill and the mechanical properties of the resulting paper were determined and compared with those of paper from a eucalyptus pulp. Despite its shortcomings, wheat straw pulp can be effectively bleached with the proposed TCF sequence.
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Oxidantes Fotoquímicos/química , Ozono/química , Papel , Triticum , Conservación de los Recursos Naturales , Ensayo de Materiales , Control de CalidadRESUMEN
The reaction kinetics of ozone bleaching of wheat straw pulp has been studied for the first time. The results were compared with eucalyptus pulp in order to know that both raw materials have a similar behaviour. Ozone treatments were carried out in a special reactor at low consistency (0.5% o.d.p.). The main variables were consumption of ozone by the pulp and application of a xylanase treatment (X) prior to the oxygen stage (O). The responses measured were kappa number, viscosity and brightness, to give the kinetic expressions for delignification, cellulose degradation and elimination of chromophore groups, along with calculation of selectivity. Cellulose degradation and elimination of lignin and chromophore groups show first-order kinetics in all cases. The kinetics of the enzyme pre-treatment effect shows similar behaviour in both raw materials, although the constants of delignification and elimination of chromophore are higher in straw pulp.
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Conservación de los Recursos Naturales , Oxidantes Fotoquímicos/química , Ozono/química , Triticum , Xilosidasas/farmacología , Cinética , Papel , Xilano Endo-1,3-beta-XilosidasaRESUMEN
OBJECTIVE: To evaluate the reliability of alcohol consumption measured by five different dietary methods in the Catalan Nutrition Survey (1992-1993). DESIGN: The different questionnaires used were: (1) two 7-day food records, (2) five items addressing alcoholic beverages in a 76-item food-frequency questionnaire, (3) a 1-week recall of 13 alcoholic beverages, (4) a 13-item alcoholic beverages frequency questionnaire and (5) two 24-hour recalls. SUBJECTS: Ninety-three of the 120 adults (aged 20 to 70 years) initially recruited completed the questionnaires and provided a peripheral blood sample. RESULTS: Mean daily alcohol intakes as assessed by the questionnaires were very similar. Beer was the alcoholic beverage most frequently consumed, followed by wine and liquor. Eighty-two per cent of the study population consumed less than 20 g of alcohol per day. No biochemical parameters were significantly correlated with alcohol intake estimated from the questionnaires. CONCLUSIONS: We found a satisfactory level of reproducibility and validity in the pattern of alcohol consumption across different levels and types of alcoholic beverage intake. We also found that the self-administered 13-item questionnaire and the 1-week recall were the best techniques to measure moderate or low alcohol consumption, suggesting that the two methods are the most suitable to assess overall alcohol intake in the general population.
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Consumo de Bebidas Alcohólicas/epidemiología , Encuestas y Cuestionarios/normas , Adulto , Anciano , Cerveza , Registros de Dieta , Femenino , Humanos , Masculino , Recuerdo Mental , Persona de Mediana Edad , Encuestas Nutricionales , Reproducibilidad de los Resultados , Autorrevelación , Sensibilidad y Especificidad , España/epidemiología , VinoRESUMEN
BACKGROUND: The World Health Organisation Collaborative Project on Alcohol and Primary Health Care has stressed the need to develop standardised screening tools to enable early identification. The aim of this study was to develop a new systematic tool to register alcohol consumption and to validate its usefulness in order to detect risky drinking in primary health care settings. SUBJECTS AND METHOD: The Systematic Interview of Alcohol Consumption (ISCA) was administered together with the Alcohol Use Disorders Identification Test (AUDIT), which was used as main external criterium, to 255 patients who attended 5 primary health care centers. RESULTS: The correlation between both procedures was highly positive and significant (r = 0.831; p < 0.001). The cut-off scores (> 28 for men and > 17 for women) showed an ISCA sensitivity rank to detect risky drinking of 70-81% for men and 46-100% for women. The ISCA specificity ranks were 82-99% and 97-100%, respectively. CONCLUSIONS: The ISCA seems to be useful to detect risky drinking and it is easy to administer by primary health care professionals. ISCA and AUDIT can be used indistinctly and complementarily.
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Alcoholismo/diagnóstico , Encuestas y Cuestionarios , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Atención Primaria de Salud , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
A prospective, multicentre study was designed to evaluate the impact of a treatment programme in alcohol-dependent patients (n = 850). Drinking status and measures related to quality of life such as morbidity, mortality, alcohol-related problems, and psychological and social functioning were assessed 5 years from the initial contact with the patient. Five years after the initial visit, drinking status followed a bimodal distribution: 371 patients (43.6%) were found to be abstinent, 323 (38%) were heavy drinkers, and only 55 (6.5%) were controlled drinkers. A total of 65 (7.6%) patients died during the study, 33 (3.9%) patients were lost to follow-up and three (0.3%) patients were not collaborative. Differences in health-related issues were identified for each of the drinking status categories. Abstinent patients presented with significantly better outcomes than controlled and heavy drinkers on most medical, socio-economic and psychological measures. Heavy drinkers showed significantly worse outcomes than controlled drinkers.
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Alcoholismo/terapia , Adolescente , Adulto , Alcoholismo/complicaciones , Alcoholismo/mortalidad , Alcoholismo/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , España/epidemiología , Templanza/psicología , Resultado del TratamientoRESUMEN
Primary intestinal T lymphoma with eosinophilia is an infrequent tumour. Its rarity account for the paucity of similar cases recorded in the literature. It affects predominantly middle-aged men and may be associated with ulceration, fistula formation and intestinal perforation with an abdominal mass. Lesions of the intestine with massive tissue eosinophilia may be a difficult diagnostic problem, but this entity displays distinctive histological features. The presence of intense tissue eosinophilia is a T-cell dependent lymphomas response. We describe a case of T lymphoma involving small intestine with massive eosinophilia.
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Eosinofilia , Neoplasias del Yeyuno/inmunología , Linfoma de Células T/inmunología , Anciano , Eosinofilia/patología , Femenino , Humanos , Neoplasias del Yeyuno/patología , Linfoma de Células T/patologíaRESUMEN
Eosinophilic gastroenteritis is a rare clinicopathogenic entity of an unknown aetiology in which a variety of digestive symptoms are associated to the eosinophilic infiltration in the intestinal wall. The clinical features depend on the site of eosinophilic infiltration, and the association with peripheral eosinophilia is very frequent. The radiologic findings were not specific and the diagnostic is based on the endoscopic and/or peroral gastrointestinal biopsy. The response to steroid therapy is spectacular. The etiology is unknown but we review the recent literature.
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Eosinofilia , Gastroenteritis , Eosinofilia/diagnóstico , Eosinofilia/etiología , Eosinofilia/patología , Eosinofilia/terapia , Gastroenteritis/diagnóstico , Gastroenteritis/etiología , Gastroenteritis/patología , Gastroenteritis/terapia , Humanos , PronósticoRESUMEN
OBJECTIVE: To estimate the frequency and characteristic of sleep disorders and consumption of hypnotic drugs in a population attended by primary care physicians (PC). METHODS: Interviewing a population of 602 patients at the office exit of 87 PC physicians in 32 institution in Mallorca 1994. Questionnaire on sleep: hypnotic drugs and scale hospital anxiety-depression, others. RESULTS: 17.4% (95% CI: 14.4%-20.5%) sleepless (DSM-III-R), 27.0% (95% CI: 23.5%-30.6%) complained from poor sleep quality and 16.4% (95% CI: 13.4%-19.4%) usually consumed hypnotic drugs (56.7%, for longer than one year). CONCLUSION: The high frequency of both sleep disorders and chronic consumption of hypnotic drugs represents a relevant health problem.
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Hipnóticos y Sedantes/uso terapéutico , Trastornos del Sueño-Vigilia/epidemiología , Adolescente , Adulto , Anciano , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Trastornos del Humor/epidemiología , Atención Primaria de Salud/estadística & datos numéricos , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Trastornos del Sueño-Vigilia/etiología , Factores Socioeconómicos , España/epidemiología , Encuestas y CuestionariosRESUMEN
Alcohol consumption seems to be decreasing in the traditional wine countries of southern Europe. This paper describes the evolution of alcohol consumption over the last 30 years in France, Greece, Italy, Portugal and Spain. For this purpose, data on alcohol production and per capita alcohol consumption in southern Europe are examined, and their reliability discussed. To analyse alcohol-related mortality, liver cirrhosis death rates are also reviewed. Since 1980 overall alcohol production has increased by 10%, while wine production has decreased by 13%. The consumption of pure alcohol equivalent per capita has continually decreased, from a peak of 14 litres per year in 1974 to 10.4 litres in 1992. The reduction is dramatic for wine (42.3%) and slight for spirits (4.7%), while beer consumption has grown by 36.6%. These data seem to confirm a European trend towards the homogenization of drinking patterns. Marketing factors, public health policies, the evolution of prices and taxation, European Union agricultural policies, a growing awareness of public opinion about the toxicity of alcohol and competition from non-alcoholic drinks are all factors that may partially explain these observed changes.