Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial

IMPORTANCE International guidelines advocate a 7- to 14-day course of systemic glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease (COPD). However, the optimal dose and duration are unknown. OBJECTIVE To investigate whether a short-term (5 days) systemic glucocorticoid treatment in patients with COPD exacerbation is noninferior to conventional (14 days) treatment in clinical outcome and whether it decreases the exposure to steroids. DESIGN, SETTING, AND PATIENTS REDUCE: (Reduction in the Use of Corticosteroids in Exacerbated COPD), a randomized, noninferiority multicenter trial in 5 Swiss teaching hospitals, enrolling 314 patients presenting to the emergency department with acute COPD exacerbation, past or present smokers (≥20 pack-years) without a history of asthma, from March 2006 through February 2011. INTERVENTIONS Treatment with 40 mg of prednisone daily for either 5 or 14 days in a placebo-controlled, double-blind fashion. The predefined noninferiority criterion was an absolute increase in exacerbations of at most 15%, translating to a critical hazard ratio of 1.515 for a reference event rate of 50%. MAIN OUTCOME AND MEASURE Time to next exacerbation within 180 days. RESULTS Of 314 randomized patients, 289 (92%) of whom were admitted to the hospital, 311 were included in the intention-to-treat analysis and 296 in the per-protocol analysis. Hazard ratios for the short-term vs conventional treatment group were 0.95 (90% CI, 0.70 to 1.29; P = .006 for noninferiority) in the intention-to-treat analysis and 0.93 (90% CI, 0.68 to 1.26; P = .005 for noninferiority) in the per-protocol analysis, meeting our noninferiority criterion. In the short-term group, 56 patients (35.9%) reached the primary end point; 57 (36.8%) in the conventional group. Estimates of reexacerbation rates within 180 days were 37.2% (95% CI, 29.5% to 44.9%) in the short-term; 38.4% (95% CI, 30.6% to 46.3%) in the conventional, with a difference of -1.2% (95% CI, -12.2% to 9.8%) between the short-term and the conventional. Among patients with a reexacerbation, the median time to event was 43.5 days (interquartile range [IQR], 13 to 118) in the short-term and 29 days (IQR, 16 to 85) in the conventional. There was no difference between groups in time to death, the combined end point of exacerbation, death, or both and recovery of lung function. In the conventional group, mean cumulative prednisone dose was significantly higher (793 mg [95% CI, 710 to 876 mg] vs 379 mg [95% CI, 311 to 446 mg], P < .001), but treatment-associated adverse reactions, including hyperglycemia and hypertension, did not occur more frequently. CONCLUSIONS AND RELEVANCE In patients presenting to the emergency department with acute exacerbations of COPD, 5-day treatment with systemic glucocorticoids was noninferior to 14-day treatment with regard to reexacerbation within 6 months of follow-up but significantly reduced glucocorticoid exposure. These findings support the use of a 5-day glucocorticoid treatment in acute exacerbations of COPD. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN19646069.

Hot QCD vs cosmology

It is a long-standing dream to “simulate” cosmology in laboratory through heavy ion collision experiments. Although the QCD epoch itself may not leave major cosmological signatures, theoretical methods developed and tested in the context of heavy ion collision experiments could indeed find applications at other energy scales. Here recent progress in this spirit is reviewed.

Aggressive vs. conservative phototherapy for infants with extremely low birth weight.

BACKGROUND: It is unclear whether aggressive phototherapy to prevent neurotoxic effects of bilirubin benefits or harms infants with extremely low birth weight (1000 g or less). METHODS: We randomly assigned 1974 infants with extremely low birth weight at 12 to 36 hours of age to undergo either aggressive or conservative phototherapy. The primary outcome was a composite of death or neurodevelopmental impairment determined for 91% of the infants by investigators who were unaware of the treatment assignments. RESULTS: Aggressive phototherapy, as compared with conservative phototherapy, significantly reduced the mean peak serum bilirubin level (7.0 vs. 9.8 mg per deciliter [120 vs. 168 micromol per liter], P<0.01) but not the rate of the primary outcome (52% vs. 55%; relative risk, 0.94; 95% confidence interval [CI], 0.87 to 1.02; P=0.15). Aggressive phototherapy did reduce rates of neurodevelopmental impairment (26%, vs. 30% for conservative phototherapy; relative risk, 0.86; 95% CI, 0.74 to 0.99). Rates of death in the aggressive-phototherapy and conservative-phototherapy groups were 24% and 23%, respectively (relative risk, 1.05; 95% CI, 0.90 to 1.22). In preplanned subgroup analyses, the rates of death were 13% with aggressive phototherapy and 14% with conservative phototherapy for infants with a birth weight of 751 to 1000 g and 39% and 34%, respectively (relative risk, 1.13; 95% CI, 0.96 to 1.34), for infants with a birth weight of 501 to 750 g. CONCLUSIONS: Aggressive phototherapy did not significantly reduce the rate of death or neurodevelopmental impairment. The rate of neurodevelopmental impairment alone was significantly reduced with aggressive phototherapy. This reduction may be offset by an increase in mortality among infants weighing 501 to 750 g at birth. (ClinicalTrials.gov number, NCT00114543.)

Internetbasierte geleitete Selbsthilfe bei verschiedenen Angststörungen: Eine randomisiert kontrollierte Studie zum Vergleich eines individualisierten vs. standardisierten Ansatzes

Hintergrund und Ziel: Internetbasierte psychotherapeutische Interventionen wurden in den letzten Jahren intensiv erforscht. Als besonders vielversprechend haben sich therapeutengeleitete Selbsthilfeprogramme bei verschiedenen Angststörungen erwiesen. Eine neue Entwicklung sind transdiagnostische und individualisierte Ansätze, in welchen auch komorbide Probleme und Störungen, und breitere Patientengruppen angesprochen werden. Beim individualisierten Ansatz werden dem Selbsthilfeprogramm in Abhängigkeit der Probleme der Patienten unterschiedliche Inhalte zugeschaltet. Das Ziel dieser Studie ist die Evaluation einer internetbasierten, individualisierten, geleiteten Selbsthilfeintervention für verschiedene Angststörungen. Methode: In einer kontrolliert-randomisierten Studie wurde der individualisierte Ansatz mit einer standardisierten Intervention, die sich nur auf die primäre Störung der Klienten bezieht, verglichen. 132 StudienteilnehmerInnen, diagnostiziert mit einer Sozialen Angststörung, Panikstörung mit oder ohne Agoraphobie, und/ oder einer Generalisierten Angststörung wurden randomisiert einer der beiden Behandlungsbedingungen oder einer Warteliste zugeteilt. Die Selbsthilfebehandlung dauerte 8 Wochen und wurde von Therapeuten via Email unterstützt. Erhebungszeitpunkte waren Prä, Post und 6 Monate nach Ende der Behandlung. Primäre Ergebnismasse sind störungsübergreifende Masse wie das Beck Angstinventar (BAI) und Daten aus einem diagnostischen Interview. Sekundäre Ergebnismasse sind störungsspezifische Fragebogen. Ergebnisse: Beide Behandlungsgruppen zeigten gegenüber der Warteliste-Kontrollgruppe signifikante Veränderungen auf allen Ergebnismassen. Auf der Basis der Intent-to-treat-Stichprobe betrugen die über die verschiedenen Ergebnismasse gemittelten Effektstärken im Vergleich zur Warteliste-Kontrollgruppe d=.80 für die individualisierte und d=.82 für die standardisierte Behandlungsbedingung. Die Symptomreduktion wurde bis zum 6-Monats-Follow-Up aufrechterhalten. Zwischen den beiden aktiven Behandlungsbedingungen wurden keine Unterschiede gefunden. Diskussion: Die Ergebnisse zeigen, dass sowohl individualisierte wie auch standardisierte internetbasierte Ansätze zur Behandlung verschiedener Angststörungen vielversprechend sind

Contrasting vulnerability and resilience to drought-induced decline of densely planted vs. natural rear-edge Pinus nigra forests

The southernmost European natural and planted pine forests are among the most vulnerable areas to warming-induced drought decline. Both drought stress and management factors (e.g., stand origin or reduced thinning) may induce decline by reducing the water available to trees but their relative importances have not been properly assessed. The role of stand origin - densely planted vs. naturally regenerated stands - as a decline driver can be assessed by comparing the growth and vigor responses to drought of similar natural vs. planted stands. Here, we compare these responses in natural and planted Black pine (Pinus nigra) stands located in southern Spain. We analyze how environmental factors - climatic (temperature and precipitation anomalies) and site conditions - and biotic factors - stand structure (age, tree size, density) and defoliation by the pine processionary moth - drive radial growth and crown condition at stand and tree levels. We also assess the climatic trends in the study area over the last 60 years. We use dendrochronology, linear mixed-effects models of basal area increment and structural equation models to determine how natural and planted stands respond to drought and current competition intensity. We observed that a temperature rise and a decrease in precipitation during the growing period led to increasing drought stress during the late 20th century. Trees from planted stands experienced stronger growth reductions and displayed more severe crown defoliation after severe droughts than those from natural stands. High stand density negatively drove growth and enhanced crown dieback, particularly in planted stands. Also pine processionary moth defoliation was more severe in the growth of natural than in planted stands but affected tree crown condition similarly in both stand types. In response to drought, sharp growth reduction and widespread defoliation of planted Mediterranean pine stands indicate that they are more vulnerable and less resilient to drought stress than natural stands. To mitigate forest decline of planted stands in xeric areas such as the Mediterranean Basin, less dense and more diverse stands should be created through selective thinning or by selecting species or provenances that are more drought tolerant. (C) 2013 Elsevier B.V. All rights reserved.

Minerale der Molybdänitlagerstätte am Alpjuhorn im Baltschiedertal (VS)

Im Zuge einer Masterarbeit an der Universität Bern und am Naturhistorischen Museum der Burger- gemeinde Bern wurde das Molybdänitvorkommen am Alpjuhorn im Baltschiedertal untersucht. Neben Molybdänit wurden auch Scheelit, Ilmenit, Galenit, Ferberit und die Sekundärmineralien Ferrimolybdit und Powellit gefunden. Speziell am Galenit des Alpjuhorns ist, dass er eine oktaedrische Spaltbar- keit aufweist. Das Auftreten von Ferberit ist insofern erwähnenswert, da aus der Schweiz nur wenige Funde von Mineralien der Wolframit-Reihe (Ferberit- Hübnerit) bekannt sind.

An index to identify stroke-related vs incidental patent foramen ovale in cryptogenic stroke

OBJECTIVE We aimed to create an index to stratify cryptogenic stroke (CS) patients with patent foramen ovale (PFO) by their likelihood that the stroke was related to their PFO. METHODS Using data from 12 component studies, we used generalized linear mixed models to predict the presence of PFO among patients with CS, and derive a simple index to stratify patients with CS. We estimated the stratum-specific PFO-attributable fraction and stratum-specific stroke/TIA recurrence rates. RESULTS Variables associated with a PFO in CS patients included younger age, the presence of a cortical stroke on neuroimaging, and the absence of these factors: diabetes, hypertension, smoking, and prior stroke or TIA. The 10-point Risk of Paradoxical Embolism score is calculated from these variables so that the youngest patients with superficial strokes and without vascular risk factors have the highest score. PFO prevalence increased from 23% (95% confidence interval [CI]: 19%-26%) in those with 0 to 3 points to 73% (95% CI: 66%-79%) in those with 9 or 10 points, corresponding to attributable fraction estimates of approximately 0% to 90%. Kaplan-Meier estimated stroke/TIA 2-year recurrence rates decreased from 20% (95% CI: 12%-28%) in the lowest Risk of Paradoxical Embolism score stratum to 2% (95% CI: 0%-4%) in the highest. CONCLUSION Clinical characteristics identify CS patients who vary markedly in PFO prevalence, reflecting clinically important variation in the probability that a discovered PFO is likely to be stroke-related vs incidental. Patients in strata more likely to have stroke-related PFOs have lower recurrence risk.