Quantifying the real life risk profile of inhaled corticosteroids in COPD by record linkage analysis

BACKGROUND: Inhaled corticosteroids (ICS), especially when prescribed in combination with long-acting β(2) agonists have been shown to improve COPD outcomes. Although there is consistent evidence linking ICS with adverse effects such as pneumonia, the complete risk profile is unclear with conflicting evidence on any association between ICS and the incidence or worsening of existing diabetes, cataracts and fractures. We investigated this using record linkage in a Dundee COPD population. METHODS: A record linkage study linking COPD and diabetes datasets with prescription, hospitalisation and mortality data via a unique Community Health Index (CHI) number. A Cox regression model was used to determine the association between ICS use and new diabetes or worsening of existing diabetes and hospitalisations for pneumonia, fractures or cataracts after adjusting for potential confounders. A time dependent analysis of exposure comparing time on versus off ICS was used to take into account patients changing their exposure status during follow-up and to prevent immortal time bias. RESULTS: 4305 subjects (3243 exposed to ICS, total of 17,229 person-years of exposure and 1062 non exposed, with a follow-up of 4,508 patient-years) were eligible for the study. There were 239 cases of new diabetes (DM) and 265 cases of worsening DM, 550 admissions for pneumonia, 288 hospitalisations for fracture and 505 cataract related admissions. The hazard ratio for the association between cumulative ICS and outcomes were 0.70 (0.43-1.12), 0.57 (0.24-1.37), 1.38 (1.09-1.74), 1.08 (0.73-1.59) and 1.42 (1.07-1.88) after multivariate analysis respectively. CONCLUSION: The use of ICS in our cohort was not associated with new onset of diabetes, worsening of existing diabetes or fracture hospitalisation. There was however an association with increased cataracts and pneumonia hospitalisations

Overtreatment of COPD with Inhaled Corticosteroids - Implications for Safety and Costs: Cross-Sectional Observational Study

<div><p>Introduction</p><p>Combined inhaled long-acting beta-agonists and corticosteroids (LABA+ICS) are costly. They are recommended in severe or very severe chronic obstructive pulmonary disease (COPD). They should not be prescribed in mild or moderate disease. In COPD ICS are associated with side-effects including risk of pneumonia. We quantified appropriateness of prescribing and examined the risks and costs associated with overuse. </p> <p>Methods</p><p>Data were extracted from the electronic and paper records of 41 London general practices (population 310,775) including spirometry, medications and exacerbations. We classified severity, assessed appropriateness of prescribing using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for 2009, and performed a sensitivity analysis using the broader recommendations of the 2011 revision.</p> <p>Results</p><p>3537 patients had a diagnosis of COPD. Spirometry was recorded for 2458(69%). 709(29%) did not meet GOLD criteria. 1749(49%) with confirmed COPD were analysed: 8.6% under-treated, 38% over-treated. Over-prescription of ICS in GOLD stage I or II (n=403, 38%) and in GOLD III or IV without exacerbations (n=231, 33.6%) was common. An estimated 12 cases (95%CI 7-19) annually of serious pneumonia were likely among 897 inappropriately treated. 535 cases of overtreatment involved LABA+ICS with a mean per patient cost of £553.56/year (€650.03). Using the broader indications for ICS in the 2011 revised GOLD guideline 25% were still classified as over-treated. The estimated risk of 15 cases of pneumonia (95%CI 8-22) in 1074 patients currently receiving ICS would rise by 20% to 18 (95%CI 9.8-26.7) in 1305 patients prescribed ICS if all with GOLD grade 3 and 4 received LABA+ICS. </p> <p>Conclusion</p><p>Over-prescription of ICS in confirmed COPD was widespread with considerable potential for harm. In COPD where treatment is often escalated in the hope of easing the burden of disease clinicians should consider both the risks and benefits of treatment and the costs where the benefits are unproven. </p> </div

Log-uniform distribution of gold deposits along major Archean fault zones

International audienceThe location of potentially unrecognized gold deposits in the close vicinity of the Cadillac-Larder Lake Fault Zone in the Archean Abitibi Subprovince (Canada) is predicted by applying a stochastic approach to the distribution of known gold deposits. The methodology uses the distances between neighboring orogenic gold deposits along the fault trace. The cumulative distribution of the curvilinear inter-distances along the fault zone, are adequately represented by a log-uniform model. The average inter-distance is 1.95 km, and an upper inter-distance of 5.6 km is observed. The same distribution pattern appears along the Destor-Porcupine Fault Zone (Abitibi). This log-uniform distribution shows that the spatial distribution of gold deposits is regionally controlled by the major crustal shear zone. Lithologies and structures only seem to exert a local influence at the deposit scale. The log-uniform spacing could be interpreted as the result of the crustal failure locations induced by hydraulic overpressure along mechanically independent segments on the main fault

Isotopic (S, Sr, Sm/Nd, H, Pb) evidences for multiple sources in the Early Jurassic Chaillac F-Ba ore deposit (Indre, France)

During the earliest Jurassic, a widespread hydrothermal event occurred in western Europe producing large veins and stratiform F-Ba-Pb-Zn ore deposits. Previous work argued about genetic processes involving circulation of mineralising brines. Two main alternative genetic models are proposed. The first one proposes a convection of brines through the crust to produce ore deposits, the second an early infiltration of brine in the basement followed by expulsion during Mesozoic extension. In the northern French Massif Central, new data on the F-Ba Chaillac deposit suggest that the genesis of these mineralising brines requires a new discussion. Located in the northern French Massif Central, the Chaillac barite and fluorite ore deposit is an exceptional site where a stratiform deposit is rooted onto a vein. The ore deposition is split in two stages: 1) precipitation of green and purple fluorite within the vein (Fg-p stage), with associated fluid inclusions indicating 135°C for deposition from a low salinity fluid, and 2) yellow fluorite and barite stage (Fy-Ba) filling the vein and forming the stratiform deposit. Fluid inclusions depict a mineralising brine at 110°C. The &lt;sup&gt;87&lt;/sup&gt;Sr/&lt;sup&gt;86&lt;/sup&gt;Sr and &lt;sup&gt;143&lt;/sup&gt;Nd/&lt;sup&gt;144&lt;/sup&gt;Nd isotopic ratios measured in the fluorite are compared to those of French Massif Central rocks. The ratios in green and purple fluorite are similar to those of monzogranite and granodiorite of the basement; those measured in yellow fluorite involve the granulites and other metamorphic rocks of the basement. Measurements of the Sr isotopic ratio and &#948;&lt;sup&gt;34&lt;/sup&gt;SCDT in barite and &#948;D in fluorite fluid inclusions suggest a deposition process by the mixing of a hydrothermal fluid with meteoric water. At the scale of the northern Massif Central district, the successive hydrothermal fluid salinities are highly contrasted as in Chaillac deposit. We propose that the two types of hydrothermal fluids have been produced by the boiling of a single fluid at depth

Petroleum Migration, Fluid Mixing, and Halokinesis as the Main Ore-Forming Processes at the Peridiapiric Jbel Tirremi Fluorite-Barite Hydrothermal Deposit, Northeastern Morocco

The Jbel Tirremi fluorite-barite ± sulfide deposit in northeastern Morocco is hosted in a Jurassic-aged structurally high carbonate platform known as the Jbel Tirremi dome. The host rocks consist of unmetamorphosed, flat-lying early Jurassic dolomitized limestones, locally intruded by Eocene lamprophyre dikes. The orebodies consist mostly of fluorite and barite, and occur as open-space fillings and partial to massive replacement of the enclosing medium- to coarse-grained dolomitized limestones. The ore mineralogy is dominated by fluorite of different colors and habits, barite, and, to a lesser extent, sulfides. Rare earth element compositions along with fluid inclusion, halogen and isotopic data suggest that the fluorite barite mineralization and the spatially associated Eocene alkaline magmatism are petrogenetically unrelated, pointing instead to the regional circulation of hydrothermal basinal brines mixed to various degrees with meteoric water in a dominantly closed rock-buffered system at progressively higher temperatures and fluid/rock ratios. In this respect, fluid inclusion microthermometric measurements show that the ore-bearing hydrothermal system developed in two separate stages of fluorite-barite mineralization, as also revealed by isotopic data. Both stages precipitated from saline fluids at shallow crustal levels (i.e., <5 km), and were related, in varying degrees, to different stages of basin evolution and salt dome growth (salt mobilization and mineralization). During the first stage, the ore fluid was a highly saline aqueous brine with a total salinity up to 44.2 wt % NaCl + KCl equiv, at temperatures ≥82°C and possibly up to 218°C, whereas in the second stage the mineralizing fluid had a similar temperature range, but lower salinities (~20–10 wt % NaCl equiv). The recorded high salinities are interpreted to represent the involvement of a mixture of halite dissolution water and evaporated seawater component. Oxygen (δ18O = 21.7 to 29.6‰ V-SMOW) and carbon (δ13C = −7.9 to 0.2‰ V-PDB) isotope data along with strontium (87Sr/86Sr = 0.70300–070789) and lead (206Pb/204Pb = 17.961–20.96, 207Pb/204Pb = 15.511–15.697, 208Pb/204Pb = 37.784–39.993) isotope ratios suggest the involvement of a mixture of oil-bearing fluids, basinal brines, and meteoric fluids that interacted extensively with the early Jurassic host carbonates, the underlying Triassic salt-bearing diapir, associated siliciclastic rocks, and the highly fractionated and greisenized Hercynian granitic crystalline basement, resulting in the release of fluoride, metals, and other constituents to form the Jbel Tirremi deposit. Petroleum-bearing fluid, released from overpressured portions of the Guercif Basin at lithostatic pressures, and bittern brines dominated the first stage of mineralization. Mixing of saline, oxidized, CaCl2- and sulfate-rich bittern brine with oil-bearing fluid resulted in fluorite precipitation of stage I. Conversely, during the second stage of mineralization, the hydrothermal system was open to the influx of oxidized meteoric water as a consequence of the upward migration of the Triassic salt-bearing diapir and associated pressure decrease. The shift from stage I to stage II is associated with the evolution of the system from lithostatic to mostly hydrostatic pressure conditions. Stage I mineralization is thought to have occurred during the Late Miocene in response to rapid sedimentation and high subsidence rates and subsequent hydrocarbon migration associated with the outward migration of the Rif thrust front. Conversely, stage II mineralization occurred coevally with the uplift phase during Tortonian time

Pulmonary lymphangiomyomatosis treated by single lung transplantation.

Pulmonary lymphangiomyomatosis is a rare disease resistant to almost all medical treatments to date. We describe the case of a 44-yr-old woman with end-stage pulmonary lymphangiomyomatosis who was treated by single-lung transplantation. The patient is doing well in her sixteenth post-transplantation month and has a marked improvement in her pulmonary function tests and walking distance as compared with preoperative values, and she is enjoying an unrestricted life-style