The impact of treatment with indacaterol in patients with COPD:A post-hoc analysis according to GOLD 2011 categories A to D

AbstractBackgroundIndacaterol is an inhaled, once-daily, ultra-long-acting β2-agonist for the treatment of chronic obstructive pulmonary disease (COPD). We report on the effectiveness of indacaterol and other bronchodilators compared with placebo in patients across the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 categories A to D.MethodsA post-hoc, subgroup pooled analysis of 6-month efficacy data from three randomized, placebo-controlled, parallel-group studies involving 3862 patients was performed across GOLD 2011 categories A to D, according to baseline forced expiratory volume in 1 s (FEV1) % predicted, modified Medical Research Council (mMRC) dyspnea scale, and exacerbation history in the 12 months prior to entry. Efficacy of once-daily indacaterol 150 and 300 μg, open-label tiotropium 18 μg, twice-daily salmeterol 50 μg, and formoterol 12 μg was compared with placebo. End points analysed were trough FEV1, transition dyspnea index (TDI), and St George's Respiratory Questionnaire (SGRQ) total score, all at Week 26, and mean rescue medication use over 26 weeks.ResultsIndacaterol 150 and 300 μg significantly improved FEV1, compared with placebo across all GOLD groups. Indacaterol 150 and 300 μg also significantly improved TDI, SGRQ total score, and mean rescue medication use compared with placebo across most GOLD subgroups.ConclusionsTreatment selection according to patient's symptoms as well as lung function is an important consideration in maintenance treatment of COPD. Indacaterol 150 and 300 μg effectively improved lung function and symptoms in patients across all GOLD 2011 categories

The impact of treatment with indacaterol in patients with COPD: A post-hoc analysis according to GOLD 2011 categories A to D

BACKGROUND: Indacaterol is an inhaled, once-daily, ultra-long-acting β2-agonist for the treatment of chronic obstructive pulmonary disease (COPD). We report on the effectiveness of indacaterol and other bronchodilators compared with placebo in patients across the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 categories A to D. METHODS: A post-hoc, subgroup pooled analysis of 6-month efficacy data from three randomized, placebo-controlled, parallel-group studies involving 3862 patients was performed across GOLD 2011 categories A to D, according to baseline forced expiratory volume in 1 s (FEV1) % predicted, modified Medical Research Council (mMRC) dyspnea scale, and exacerbation history in the 12 months prior to entry. Efficacy of once-daily indacaterol 150 and 300 μg, open-label tiotropium 18 μg, twice-daily salmeterol 50 μg, and formoterol 12 μg was compared with placebo. End points analysed were trough FEV1, transition dyspnea index (TDI), and St George's Respiratory Questionnaire (SGRQ) total score, all at Week 26, and mean rescue medication use over 26 weeks. RESULTS: Indacaterol 150 and 300 μg significantly improved FEV1, compared with placebo across all GOLD groups. Indacaterol 150 and 300 μg also significantly improved TDI, SGRQ total score, and mean rescue medication use compared with placebo across most GOLD subgroups. CONCLUSIONS: Treatment selection according to patient's symptoms as well as lung function is an important consideration in maintenance treatment of COPD. Indacaterol 150 and 300 μg effectively improved lung function and symptoms in patients across all GOLD 2011 categories

Mindfulness-based interventions in epilepsy: a systematic review

Mindfulness based interventions (MBIs) are increasingly used to help patients cope with physical and mental long-term conditions (LTCs). Epilepsy is associated with a range of mental and physical comorbidities that have a detrimental effect on quality of life (QOL), but it is not clear whether MBIs can help. We systematically reviewed the literature to determine the effectiveness of MBIs in people with epilepsy. Medline, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, Allied and Complimentary Medicine Database, and PsychInfo were searched in March 2016. These databases were searched using a combination of subject headings where available and keywords in the title and abstracts. We also searched the reference lists of related reviews. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Three randomised controlled trials (RCTs) with a total of 231 participants were included. The interventions were tested in the USA (n = 171) and China (Hong Kong) (n = 60). Significant improvements were reported in depression symptoms, quality of life, anxiety, and depression knowledge and skills. Two of the included studies were assessed as being at unclear/high risk of bias - with randomisation and allocation procedures, as well as adverse events and reasons for drop-outs poorly reported. There was no reporting on intervention costs/benefits or how they affected health service utilisation. This systematic review found limited evidence for the effectiveness of MBIs in epilepsy, however preliminary evidence suggests it may lead to some improvement in anxiety, depression and quality of life. Further trials with larger sample sizes, active control groups and longer follow-ups are needed before the evidence for MBIs in epilepsy can be conclusively determined

PRIMA1 mutation: A new cause of nocturnal frontal lobe epilepsy

Objective Nocturnal frontal lobe epilepsy (NFLE) can be sporadic or autosomal dominant; some families have nicotinic acetylcholine receptor subunit mutations. We report a novel autosomal recessive phenotype in a single family and identify the causative gene. Methods Whole exome sequencing data was used to map the family, thereby narrowing exome search space, and then to identify the mutation. Results Linkage analysis using exome sequence data from two affected and two unaffected subjects showed homozygous linkage peaks on chromosomes 7, 8, 13, and 14 with maximum LOD scores between 1.5 and 1.93. Exome variant filtering under these peaks revealed that the affected siblings were homozygous for a novel splice site mutation (c.93+2T>C) in the PRIMA1 gene on chromosome 14. No additional PRIMA1 mutations were found in 300 other NFLE cases. The c.93+2T>C mutation was shown to lead to skipping of the first coding exon of the PRIMA1 mRNA using a minigene system. Interpretation PRIMA1 is a transmembrane protein that anchors acetylcholinesterase (AChE), an enzyme hydrolyzing acetycholine, to membrane rafts of neurons. PRiMA knockout mice have reduction of AChE and accumulation of acetylcholine at the synapse; our minigene analysis suggests that the c.93+2T>C mutation leads to knockout of PRIMA1. Mutations with gain of function effects in acetylcholine receptor subunits cause autosomal dominant NFLE. Thus, enhanced cholinergic responses are the likely cause of the severe NFLE and intellectual disability segregating in this family, representing the first recessive case to be reported and the first PRIMA1 mutation implicated in disease

Epidemic infectious gastrointestinal illness aboard U.S. Navy ships deployed to the Middle East during peacetime operations – 2000–2001

BACKGROUND: Infectious gastrointestinal illness (IGI) outbreaks have been reported in U.S. Navy ships and could potentially have an adverse mission impact. Studies to date have been anecdotal. METHODS: We conducted a retrospective analysis of weekly reported disease and non-battle injury health data collected in 2000 – 2001 from 44 U.S. Navy ships while sailing in the 5(th )Fleet (Persian Gulf and nearby seas). RESULTS: During this period, 11 possible IGI outbreaks were identified. Overall, we found 3.3 outbreaks per 100 ship-weeks, a mean outbreak duration of 4.4 weeks, and a mean cumulative ship population attack rate of 3.6%. Morbidity, represented by days lost due to personnel being placed on sick-in-quarters status, was higher during outbreak weeks compared to non-outbreak weeks (p = 0.002). No clear seasonal distribution was identified. CONCLUSION: Explosive outbreaks due to viruses and bacteria with the potential of incapacitating large proportions of the crew raise serious concerns of mission impact and military readiness

Long telomeres are associated with clonality in wild populations of the fissiparous starfish Coscinasterias tenuispina

7 páginas, 4 figuras, 3 tablasTelomeres usually shorten during an organism’s lifespan and have thus been used as an aging and health marker. When telomeres become sufficiently short, senescence is induced. The most common method of restoring telomere length is via telomerase reverse transcriptase activity, highly expressed during embryogenesis. However, although asexual reproduction from adult tissues has an important role in the life cycles of certain species, its effect on the aging and fitness of wild populations, as well as its implications for the long-term survival of populations with limited genetic variation, is largely unknown. Here we compare relative telomere length of 58 individuals from four populations of the asexually reproducing starfish Coscinasterias tenuispina. Additionally, 12 individuals were used to compare telomere lengths in regenerating and non-regenerating arms, in two different tissues (tube feet and pyloric cecum). The level of clonality was assessed by genotyping the populations based on 12 specific microsatellite loci and relative telomere length was measured via quantitative PCR. The results revealed significantly longer telomeres in Mediterranean populations than Atlantic ones as demonstrated by the Kruskal–Wallis test (K=24.17, significant value: P-valueo0.001), with the former also characterized by higher levels of clonality derived from asexual reproduction. Telomeres were furthermore significantly longer in regenerating arms than in non-regenerating arms within individuals (pyloric cecum tissue: Mann–Whitney test, V=299, P-valueo10− 6; and tube feet tissue Student's t= 2.28, P-value =0.029). Our study suggests that one of the mechanisms responsible for the long-term somatic maintenance and persistence of clonal populations is telomere elongation.This research was financially supported by a PhD fellowship FPI-MICINN (BES-2011-044154) (ACG), the European ASSEMBLY project (227799), the Swedish Royal Academy of Sciences (ACG) and the Spanish Government project CTM2010-22218-C02. The research was also supported by a ‘Juan de la Cierva’ contract from the Spanish Government (RPP) and by the Adlerbertska Research Foundation (HNS).Peer reviewe

Anticoagulant selection in relation to the SAMe-TT2R2 score in patients with atrial fibrillation. the GLORIA-AF registry

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007