Comparative efficacy of long-acting bronchodilators for COPD - a network meta-analysis

Background: Clinicians are faced with an increasingly difficult choice regarding the optimal bronchodilator for patients with chronic obstructive pulmonary disease (COPD) given the number of new treatments. The objective of this study is to evaluate the comparative efficacy of indacaterol 75/150/300 μg once daily (OD), glycopyrronium bromide 50 μg OD, tiotropium bromide 18 μg/5 μg OD, salmeterol 50 μg twice daily (BID), formoterol 12 μg BID, and placebo for moderate to severe COPD. Methods: Forty randomized controlled trials were combined in a Bayesian network meta-analysis. Outcomes of interest were trough and post-dose forced expiratory volume in 1 second (FEV1), St. George’s Respiratory Questionnaire (SGRQ) score and responders (≥4 points), and Transition Dyspnea Index (TDI) score and responders (≥1 point) at 6 months. Results: Indacaterol was associated with a higher trough FEV1 than other active treatments (difference for indacaterol 150 μg and 300 μg versus placebo: 152 mL (95% credible interval (CrI): 126, 179); 160 mL (95% CrI: 133, 187)) and the greatest improvement in SGRQ score (difference for indacaterol 150 μg and 300 μg versus placebo: -3.9 (95% CrI -5.2, -2.6); -3.6 (95% CrI -4.8, -2.3)). Glycopyrronium and tiotropium 18 μg resulted in the next best estimates for both outcomes with minor differences (difference for glycopyrronium versus tiotropium for trough FEV1 and SGRQ: 18 mL (95% CrI: -16, 51); -0.55 (95% CrI: -2.04, 0.92). Conclusion: In terms of trough FEV1 and SGRQ score indacaterol, glycopyrronium, and tiotropium are expected to be the most effective bronchodilators

Correlating changes in lung function with patient outcomes in chronic obstructive pulmonary disease: a pooled analysis

Background Relationships between improvements in lung function and other clinical outcomes in chronic obstructive pulmonary disease (COPD) are not documented extensively. We examined whether changes in trough forced expiratory volume in 1 second (FEV1) are correlated with changes in patient-reported outcomes. Methods Pooled data from three indacaterol studies (n = 3313) were analysed. Means and responder rates for outcomes including change from baseline in Transition Dyspnoea Index (TDI), St. George's Respiratory Questionnaire (SGRQ) scores (at 12, 26 and 52 weeks), and COPD exacerbation frequency (rate/year) were tabulated across categories of ΔFEV1. Also, generalised linear modelling was performed adjusting for covariates such as baseline severity and inhaled corticosteroid use. Results With increasing positive ΔFEV1, TDI and ΔSGRQ improved at all timepoints, exacerbation rate over the study duration declined (P < 0.001). Individual-level correlations were 0.03-0.18, but cohort-level correlations were 0.79-0.95. At 26 weeks, a 100 ml increase in FEV1 was associated with improved TDI (0.46 units), ΔSGRQ (1.3-1.9 points) and exacerbation rate (12% decrease). Overall, adjustments for baseline covariates had little impact on the relationship between ΔFEV1 and outcomes. Conclusions These results suggest that larger improvements in FEV1 are likely to be associated with larger patient-reported benefits across a range of clinical outcomes

Retroperitoneal lymph node dissection (RPLND) for malignant phenotype Leydig cell tumours of the testis: a 10-year experience.

Retroperitoneal lymph node dissection (RPLND) is a prognostic, palliative, and potentially therapeutic procedure for patients with malignant phenotype Leydig cell tumours of the testis. We reviewed the records of patients diagnosed with malignant phenotype Leydig cell tumours of the testis treated by RPLND. Modified template dissection was performed in all cases with extra-template excision of tumour mass in Stage II disease. Routine clinico-radiological follow-up was performed. Six open RPLNDs (1 re-do procedure) were performed on 5 patients diagnosed with Stage I (n = 3) and Stage II (n = 2) malignant phenotype Leydig cell tumour of the testis. Median age = 63 years (range = 55-72). Median peri-operative blood loss = 1500 ml (range = 500-1500 ml). Median operating time = 6 h (range = 4.5-6.5). Two patients with Stage II disease developed post-operative complications of acute kidney injury (n = 1) and pneumonia (n = 1). Median length of stay was 8 days (range = 6-11). RPLND specimens from patients with Stage I were tumour-free, whilst patients with Stage II disease had evidence of metastatic tumour. At latest follow-up (median = 13 months, range = 7-22), no patient with Stage I disease had radiological evidence of recurrence, however the two patients with Stage II disease had died due to tumour recurrence at 13 months and 36 months. RPLND for malignant phenotype Leydig cell testicular tumours appears to be well tolerated. Despite surgery, overall outcomes for Stage II appear to be poor due to the disease phenotype. Larger prospective multi-centre studies are required to determine the definitive criteria for surgery in Stage I disease

Free abdominal fluid without obvious solid organ injury upon CT imaging: an actual problem or simply over-diagnosing?

Whereas a non-operative approach for hemodynamically stable patients with free intraabdominal fluid in the presence of solid organ injury is generally accepted, the presence of free fluid in the abdomen without evidence of solid organ injury not only presents a challenge for the treating emergency physician but also for the surgeon in charge. Despite recent advances in imaging modalities, with multi-detector computed tomography (CT) (with or without contrast agent) usually the imaging method of choice, diagnosis and interpretation of the results remains difficult. While some studies conclude that CT is highly accurate and relatively specific at diagnosing mesenteric and hollow viscus injury, others studies deem CT to be unreliable. These differences may in part be due to the experience and the interpretation of the radiologist and/or the treating physician or surgeon

Employing an open-source tool to assess astrocyte tridimensional structure

Astrocytes display important features that allow them to maintain a close dialog with neurons, ultimately impacting brain function. The complex morphological structure of astrocytes is crucial to the role of astrocytes in brain networks. Therefore, assessing morphologic features of astrocytes will help provide insights into their physiological relevance in healthy and pathological conditions. Currently available tools that allow the tridimensional reconstruction of astrocytes present a number of disadvantages, including the need for advanced computational skills and powerful hardware, and are either time-consuming or costly. In this study, we optimized and validated the FIJI-ImageJ, Simple Neurite Tracer (SNT) plugin, an open-source software that aids in the reconstruction of GFAP-stained structure of astrocytes. We describe (1) the loading of confocal microscopy Z-stacks, (2) the selection criteria, (3) the reconstruction process, and (4) the post-reconstruction analysis of morphological features (process length, number, thickness, and arbor complexity). SNT allows the quantification of astrocyte morphometric parameters in a simple, efficient, and semi-automated manner. While SNT is simple to learn, and does not require advanced computational skills, it provides reproducible results, in different brain regions or pathophysiological states.The authors acknowledge funding from national funds through the FCT—Foundation for Science and Technology—project (PTDC/SAU-NSC/118194/2010) to G.T., V.M.S., S.G.G. and J.F.O., and fellowships (SFRH/BD/89714/2012 to V.M.S., SFRH/BPD/97281/2013 to J.F.O., SFRH/BD/101298/2014 to S.G.G., PD/BD/114120/2015 to S.P.N, and PD/BD/127822/2016 to G.T.); Marie Curie Fellowship FP7-PEOPLE-2010-IEF 273936 and BIAL Foundation Grants and 207/14 to J.F.O.; QREN and FEDER funds through Operational program for competitiveness factors—COMPETE, “ON.2 SR&TD Integrated Program—NORTE-07-0124-FEDER-000021”; National and European funds through FCT, and FEDER through COMPETE (PEst-C/SAU/LA0026/2011 and FCOMP-01-0124-FEDER-022724; PEst-C/SAU/LA0026/2013 and FCOMP-01-0124-FEDER-037298, respectively)info:eu-repo/semantics/publishedVersio

A systematic review of interventions to increase awareness of mental health and well-being in athletes, coaches and officials

Full search for the psychinfo database. (DOCX 16 kb

Adaptive Value of Phenological Traits in Stressful Environments: Predictions Based on Seed Production and Laboratory Natural Selection

Phenological traits often show variation within and among natural populations of annual plants. Nevertheless, the adaptive value of post-anthesis traits is seldom tested. In this study, we estimated the adaptive values of pre- and post-anthesis traits in two stressful environments (water stress and interspecific competition), using the selfing annual species Arabidopsis thaliana. By estimating seed production and by performing laboratory natural selection (LNS), we assessed the strength and nature (directional, disruptive and stabilizing) of selection acting on phenological traits in A. thaliana under the two tested stress conditions, each with four intensities. Both the type of stress and its intensity affected the strength and nature of selection, as did genetic constraints among phenological traits. Under water stress, both experimental approaches demonstrated directional selection for a shorter life cycle, although bolting time imposes a genetic constraint on the length of the interval between bolting and anthesis. Under interspecific competition, results from the two experimental approaches showed discrepancies. Estimation of seed production predicted directional selection toward early pre-anthesis traits and long post-anthesis periods. In contrast, the LNS approach suggested neutrality for all phenological traits. This study opens questions on adaptation in complex natural environment where many selective pressures act simultaneously

Investigation of the Climatic and Environmental Context of Hendra Virus Spillover Events 1994–2010

Hendra virus is a recently emerged bat-borne zoonotic agent with high lethality in horses and humans in Australia. This is a rare disease and the determinants of bat to horse transmission, including the factors that bring these hosts together at critical times, are poorly understood. In this cross-disciplinary study climatic and vegetation primary productivity variables are compared for the dispersed and heterogenic 1994–2010 outbreak sites. The significant occurrence of spillover events within the dry season (p =  0.013, 95% CI (0.57–0.98)) suggests seasonal forcing of transmission across species, or seasonal forcing of virus excretion by the reservoir host. We explore the evidence for both. Preliminary investigations of the spatial determinants of Hendra disease locations are also presented. We find that postal areas in the Australian state of Queensland in which pteropid fruit bat (flying fox) roosts occur are approximately forty times more likely (OR = 40.5, (95% CI (5.16, 317.52)) to be the location of Hendra spillover events. This appears to be independent of density of horses at these locations. We consider issues of scale of host resource use, land use change and limitations of existing data that challenge analysis and limit further conclusive outcomes. This investigation of a broad range of potential climatic and environmental influences provides a good base for future investigations. Further understanding of cross-species Hendra virus transmission requires better understanding of flying fox resource use in the urban-rural landscape