Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety

<p>Background: Melatonin is extensively used in the USA in a non-regulated manner for sleep disorders. Prolonged release melatonin (PRM) is licensed in Europe and other countries for the short term treatment of primary insomnia in patients aged 55 years and over. However, a clear definition of the target patient population and well-controlled studies of long-term efficacy and safety are lacking. It is known that melatonin production declines with age. Some young insomnia patients also may have low melatonin levels. The study investigated whether older age or low melatonin excretion is a better predictor of response to PRM, whether the efficacy observed in short-term studies is sustained during continued treatment and the long term safety of such treatment.</p> <p>Methods: Adult outpatients (791, aged 18-80 years) with primary insomnia, were treated with placebo (2 weeks) and then randomized, double-blind to 3 weeks with PRM or placebo nightly. PRM patients continued whereas placebo completers were re-randomized 1:1 to PRM or placebo for 26 weeks with 2 weeks of single-blind placebo run-out. Main outcome measures were sleep latency derived from a sleep diary, Pittsburgh Sleep Quality Index (PSQI), Quality of Life (World Health Organzaton-5) Clinical Global Impression of Improvement (CGI-I) and adverse effects and vital signs recorded at each visit.</p> <p>Results: On the primary efficacy variable, sleep latency, the effects of PRM (3 weeks) in patients with low endogenous melatonin (6-sulphatoxymelatonin [6-SMT] ≤8 μg/night) regardless of age did not differ from the placebo, whereas PRM significantly reduced sleep latency compared to the placebo in elderly patients regardless of melatonin levels (-19.1 versus -1.7 min; P = 0.002). The effects on sleep latency and additional sleep and daytime parameters that improved with PRM were maintained or enhanced over the 6-month period with no signs of tolerance. Most adverse events were mild in severity with no clinically relevant differences between PRM and placebo for any safety outcome.</p> <p>Conclusions: The results demonstrate short- and long-term efficacy and safety of PRM in elderly insomnia patients. Low melatonin production regardless of age is not useful in predicting responses to melatonin therapy in insomnia. The age cut-off for response warrants further investigation.</p&gt

Correction: Pulsed moxifloxacin for the prevention of exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial

BACKGROUND: Acute exacerbations contribute to the morbidity and mortality associated with chronic obstructive pulmonary disease (COPD). This proof-of-concept study evaluates whether intermittent pulsed moxifloxacin treatment could reduce the frequency of these exacerbations. METHODS: Stable patients with COPD were randomized in a double-blind, placebo-controlled trial to receive moxifloxacin 400 mg PO once daily (N = 573) or placebo (N = 584) once a day for 5 days. Treatment was repeated every 8 weeks for a total of six courses. Patients were repeatedly assessed clinically and microbiologically during the 48-week treatment period, and for a further 24 weeks' follow-up. RESULTS: At 48 weeks the odds ratio (OR) for suffering an exacerbation favoured moxifloxacin: per-protocol (PP) population (N = 738, OR 0.75, 95% confidence interval (CI) 0.565-0.994, p = 0.046), intent-to-treat (ITT) population (N = 1149, OR 0.81, 95% CI 0.645-1.008, p = 0.059), and a post-hoc analysis of per-protocol (PP) patients with purulent/mucopurulent sputum production at baseline (N = 323, OR 0.55, 95% CI 0.36-0.84, p = 0.006).There were no significant differences between moxifloxacin and placebo in any pre-specified efficacy subgroup analyses or in hospitalization rates, mortality rates, lung function or changes in St George's Respiratory Questionnaire (SGRQ) total scores. There was, however, a significant difference in favour of moxifloxacin in the SGRQ symptom domain (ITT: -8.2 vs -3.8, p = 0.009; PP: -8.8 vs -4.4, p = 0.006). Moxifloxacin treatment was not associated with consistent changes in moxifloxacin susceptibility. There were more treatment-emergent, drug related adverse events with moxifloxacin vs placebo (p < 0.001) largely due to gastrointestinal events (4.7% vs 0.7%). CONCLUSIONS: Intermittent pulsed therapy with moxifloxacin reduced the odds of exacerbation by 20% in the ITT population, by 25% among the PP population and by 45% in PP patients with purulent/mucopurulent sputum at baseline. There were no unexpected adverse events and there was no evidence of resistance development. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00473460 (ClincalTrials.gov)

Mindfulness-based cognitive therapy for psychological distress in pregnancy: study protocol for a randomized controlled trial

BACKGROUND: Clinically significant psychological distress in pregnancy is common, with epidemiological research suggesting that between 15 and 25 % of pregnant women experience elevated symptoms of stress, anxiety, and depression. Untreated psychological distress in pregnancy is associated with poor obstetrical outcomes, changes in maternal physiology, elevated incidence of child physical and psychological disorders, and is predictive of maternal postpartum mood disorders. Despite the wide-ranging impact of antenatal psychological distress on mothers and their children, there is a gap in our knowledge about the most effective treatments that are available for psychological distress experienced in pregnancy. Additionally, no trials have focused on potential physiological changes that may occur as a result of receiving mindfulness training in pregnancy. The proposed trial will determine the effectiveness of an 8-week modified Mindfulness-based Cognitive Therapy (MBCT) intervention delivered during pregnancy. METHODS: A randomized controlled trial (RCT) design with repeated measures will be used to evaluate the effectiveness of MBCT to treat psychological distress in pregnancy. A sample of 60 consenting pregnant women aged 18 years and above will be enrolled and randomized to the experimental (MBCT) or control (treatment as usual) condition. Primary (e.g., symptoms of stress, depression, and anxiety), secondary (cortisol, blood pressure (BP), heart rate variability (HRV), and sleep) and other outcome data (e.g., psychological diagnoses) will be collected via a combination of laboratory visits and at-home assessments from both groups at baseline (T(1)), immediately following the intervention (T(2)), and at 3 months postpartum (T(3)). Descriptive statistics will be used to describe sample characteristics. Data will be analyzed using an intention-to-treat approach. Hierarchical linear models will be used to test intervention effects on primary and secondary outcomes. DISCUSSION: The trial is expected to improve knowledge about evidence-based treatments for psychological distress experienced in pregnancy and to evaluate the potential impact of mindfulness-based interventions on maternal physiology. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02214732, registered on 7 August 2014. Protocol Version 2.0., 5 September 2016. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-016-1601-0) contains supplementary material, which is available to authorized users

Legitimacy, Visibility, and the Antecedents of Corporate Social Performance: An Investigation of the Instrumental Perspective

Using institutional theory as the foundation, this study examines the role of organizational visibility from a variety of sources (i.e., slack visibility, industry visibility, and visibility to multiple stakeholders) in influencing corporate social performance (CSP). The conceptual framework offers important insights regarding the instrumental motives of managers in performing CSP initiatives. Based on a sample of 124 S&P 500 firms, the authors found that it is a firm’s visibility to stakeholders, rather than its economic performance, that has the larger impact on managers’ decisions regarding how much CSP their firms exhibit. The results show that more profitable firms may not be motivated to engage actively in CSP unless they are under greater scrutiny by various firm stakeholders. The authors also found that organizational slack (estimated as cost of capital) is positively associated with a Social CSP dimension but negatively associated with a Strategic CSP dimension. This research contributes to the current CSP literature by demonstrating that motivations in addition to normative or ethical ones may be at play in the decisions firms make regarding their CSP.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Desempenho ocupacional das famílias cuidadoras de pessoas com transtornos mentais atendidas em dispositivo de atenção psicossocial

With the process of psychiatric institutionalization, treatment of people with mental disorders, characterized by long before psychiatric hospitalizations, chronicity and social exclusion, went on to defend the humanized care, the integration of the individual in the family and society. The family of the person with a mental disorder, for a considerable time was excluded from the assistance provided to his family. He is currently an important partner of care, since most people who were treated in closed institutions, today live daily with their caregivers, at home. However, families often are not prepared to act as caretakers of close family members with mental disorders, and thus experience a context of overloads in everyday life. It is not uncommon the fact they have not with satisfactory support to deal with the complex situation of caring for a relative who needs care at length in daily life. This research aims to describe the areas of occupational performance (work, rest and sleep, leisure and social participation), the caregivers families before and after the mental illness of his family and the repercussions of this fact in daily life and living conditions of family caregivers; Identify among the areas of occupational performance (work, rest and sleep, leisure and social participation), those considered most important for family caregivers, and the strategies used by them for the development of these areas, with a view to changes in their daily lives and their living conditions. This is a qualitative, critical and reflective study. Approved by the Research Ethics Committee (CEP) of the University Hospital Lauro Wanderley the Federal University of Paraíba, in the period from July 2014 to February 2015. The instrument for data collection was semi-structured interviews. Data collection took place in October and November 2014, after receiving the assent of the CEP. The material was subjected to the analysis of data according to Minayo (2008), following three methodological steps: pre-analysis, material exploration, processing of data and interpretation. The research findings revealed that with regard to the areas of occupational performance (work, rest and sleep, leisure and social participation) of family before becoming caregivers, four of them worked before the mental illness of their relatives and family, by the will of spouse, only performed housework. With regard to rest and sleep, the five family caregivers, two reported not enjoy a good rest and sleep before getting sick of your family, a fact surely occasioned negative impact on the dynamics of your everyday life . The other three caregivers had a good rest and sleep. It was identified that the leisure of the caregivers in this study, before the mental illness of the family, was designed and related to diverse aspects. The five family caregivers interviewed reported an active social participation, whether in church, community groups, in the family. With regard to the areas of occupational performance after mental illness the family, all family caregivers have had to stop work activities outside the home to care for relatives with mental disorders. The rest and sleep of them had to suffer. The leisure and social participation of family caregivers were determined by dynamic behavior of their relatives with mental disorders. With regard to the areas of occupational performance considered the most important by family caregivers, they elected two: rest and sleep and social participation. With the completion of this study, we can see the relevance of the intervention of health workers, because through dialogue and more systematic follow-up to these families, you can help minimize the impact of a life in organized care and overloads generated by these care and so contribute to improving the quality of life of families and caregivers also of users with mental disorders.Com o processo de desinstitucionalização psiquiátrica, o tratamento das pessoas com transtornos mentais antes caracterizados por longas internações psiquiátricas, cronificação e exclusão social, passou a defender o cuidado humanizado, a reinserção do indivíduo na família e na sociedade. A família da pessoa com transtorno mental, durante tempo considerável foi excluída da assistência prestada ao seu familiar. Atualmente é uma importante parceira do cuidado, pois muitas pessoas que eram tratadas em instituições fechadas, hoje convivem diariamente com seus cuidadores, no domicílio. Porém, as famílias, muitas vezes, não estão preparadas para atuar como cuidadoras desses familiares com transtornos mentais, e assim vivenciam um contexto de sobrecargas no cotidiano. Não é raro o fato de não contarem com suporte satisfatório para lidar com a complexa situação de cuidar de um familiar, o qual necessita de cuidados durante um tempo considerável no cotidiano. Esta pesquisa tem como objetivo descrever as áreas de desempenho ocupacional (trabalho; descanso e sono; lazer e participação social), das famílias cuidadoras, antes e após o adoecimento mental dos seus familiares e as repercussões desse fato no cotidiano e nas condições de vida dos familiares cuidadores; Identificar dentre as áreas de desempenho ocupacional (trabalho; descanso e sono; lazer e participação social), as que são consideradas mais importantes para os familiares cuidadores, e as estratégias utilizadas por eles para o desenvolvimento dessas áreas, com vistas a mudanças no seu cotidiano e nas suas condições de vida. Trata-se de estudo qualitativo, crítico e reflexivo. Aprovado pelo Comitê de Ética e Pesquisa (CEP) do Hospital Universitário Lauro Wanderley da Universidade Federal da Paraíba, desenvolvido no período de julho de 2014 a fevereiro de 2015. O instrumento para coleta de dados foi a entrevista semiestruturada. A coleta de dados aconteceu nos meses de outubro e novembro de 2014, após recebimento do parecer favorável do CEP. O material foi submetido a análise de dados segundo Minayo (2008), seguindo três passos metodológicos: pré-análise, exploração do material, tratamento dos dados obtidos e interpretação. Os achados da pesquisa revelaram que no tocante às áreas de desempenho ocupacional (trabalho, descanso e sono, lazer e participação social) dos familiares antes de se tornarem cuidadores, quatro delas trabalhavam antes do adoecimento mental de seus familiares e uma familiar, por vontade do esposo, só realizava trabalhos domésticos. No que diz respeito ao descanso e sono, das cinco cuidadoras familiares, duas relataram não desfrutarem de um bom descanso e sono, antes do processo de adoecimento do seu familiar, fato este, com certeza, que ocasionava repercussões negativas na dinâmica de seu dia a dia. As outras três cuidadoras apresentavam bom descanso e sono. Identificou-se que o lazer das cuidadoras desse estudo, antes do adoecimento mental do familiar, era concebido e relacionado a aspectos diversificados. As cinco cuidadoras familiares entrevistadas relataram uma participação social atuante, seja na igreja, nos grupos comunitários e na família. No que diz respeito às áreas de desempenho ocupacional após o adoecimento mental do familiar, todas as cuidadoras familiares tiveram de interromper as atividades de trabalho fora de casa para cuidar de familiares com transtornos mentais. O descanso e sono delas apresentavam-se prejudicados. O lazer e a participação social das cuidadoras familiares eram determinados pela dinâmica de comportamento dos seus familiares com transtornos mentais. No concernente às áreas de desempenho ocupacional consideradas as mais importantes pelas cuidadoras familiares, estas elegeram duas: descanso e sono e participação social. Com a realização desse estudo, percebe-se a relevância da intervenção dos trabalhadores da saúde, pois mediante o diálogo e acompanhamento mais sistemático a essas famílias, pode-se contribuir para minimizar o impacto de uma vida organizada em cuidados e sobrecargas geradas por esses cuidados e assim colaborar para a melhoria da qualidade de vida das famílias cuidadoras e também dos usuários com transtornos mentais

Ethanol causes the redistribution of L1 cell adhesion molecule in lipid rafts

10.1111/j.1471-4159.2011.07467.xJournal of Neurochemistry1194859-867JONR