Inflammation appears to play a role in atherosclerosis, raising the possibility that treatments that reduce inflammation could prevent cardiovascular events. In a randomized, placebo-controlled trial ...involving 4745 patients with recent myocardial infarction, low-dose colchicine (0.5 mg once daily) prevented ischemic cardiovascular events.
Abstract
Aims
The COLchicine Cardiovascular Outcomes Trial (COLCOT) demonstrated the benefits of targeting inflammation after myocardial infarction (MI). We aimed to determine whether ...time-to-treatment initiation (TTI) influences the beneficial impact of colchicine.
Methods and results
In COLCOT, patients were randomly assigned to receive colchicine or placebo within 30 days post-MI. Time-to-treatment initiation was defined as the length of time between the index MI and the initiation of study medication. The primary efficacy endpoint was a composite of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring coronary revascularization. The relationship between endpoints and various TTI (<3, 4–7 and >8 days) was examined using multivariable Cox regression models. Amongst the 4661 patients included in this analysis, there were 1193, 720, and 2748 patients, respectively, in the three TTI strata. After a median follow-up of 22.7 months, there was a significant reduction in the incidence of the primary endpoint for patients in whom colchicine was initiated < Day 3 compared with placebo hazard ratios (HR) = 0.52, 95% confidence intervals (CI) 0.32–0.84, in contrast to patients in whom colchicine was initiated between Days 4 and 7 (HR = 0.96, 95% CI 0.53–1.75) or > Day 8 (HR = 0.82, 95% CI 0.61–1.11). The beneficial effects of early initiation of colchicine were also demonstrated for urgent hospitalization for angina requiring revascularization (HR = 0.35), all coronary revascularization (HR = 0.63), and the composite of cardiovascular death, resuscitated cardiac arrest, MI, or stroke (HR = 0.55, all P < 0.05).
Conclusion
Patients benefit from early, in-hospital initiation of colchicine after MI.
Trial Registration
COLCOT ClinicalTrials.gov number, NCT02551094.
Graphical Abstract
Tree-killing bark beetles are the most economically important insects in conifer forests worldwide. However, despite >200 years of research, the drivers of population eruptions and crashes are still ...not fully understood and the existing knowledge is thus insufficient to face the challenges posed by the Anthropocene. We critically analyze potential biotic and abiotic drivers of population dynamics of an exemplary species, the European spruce bark beetle (ESBB) (Ips typographus) and present a multivariate approach that integrates the many drivers governing this bark beetle system. We call for hypothesis-driven, large-scale collaborative research efforts to improve our understanding of the population dynamics of this and other bark beetle pests. Our approach can serve as a blueprint for tackling other eruptive forest insects.
Bark beetles are currently causing unprecedented damage to European and North American forests.Their population dynamics rarely have been studied in a hypothesis-driven manner incorporating exogenous biotic variables.We propose a conceptual framework to reveal the drivers of bark beetle populations.This approach can be equally applied to other eruptive insect pests.
Bark beetles are among the most devastating biotic agents affecting forests globally and several species are expected to be favored by climate change. Given the potential interactions of insect ...outbreaks with other biotic and abiotic disturbances, and the potentially strong impact of changing disturbance regimes on forest resources, investigating climatic drivers of destructive bark beetle outbreaks is of paramount importance. We analyzed 17 time‐series of the amount of wood damaged by Ips typographus, the most destructive pest of Norway spruce forests, collected across 8 European countries in the last three decades. We aimed to quantify the relative importance of key climate drivers in explaining timber loss dynamics, also testing for possible synergistic effects. Local outbreaks shared the same drivers, including increasing summer rainfall deficit and warm temperatures. Large availability of storm‐felled trees in the previous year was also strongly related to an increase in timber loss, likely by providing an alternative source of breeding material. We did not find any positive synergy among outbreak drivers. On the contrary, the occurrence of large storms reduced the positive effect of warming temperatures and rainfall deficit. The large surplus of breeding material likely boosted I. typographus population size above the density threshold required to colonize and kill healthy trees irrespective of other climate triggers. Importantly, we found strong negative density dependence in I. typographus that may provide a mechanism for population decline after population eruptions. Generality in the effects of complex climatic events across different geographical areas suggests that the large‐scale drivers can be used as early warning indicators of increasing local outbreak probability.
Aim: Invasive alien species (IAS) are recognized as major drivers of biodiversity loss, but few causal relationships between IAS and species declines have been documented. In this study, we compare ...the distribution (Belgium and Britain) and abundance (Belgium, Britain and Switzerland) of formerly common and widespread native ladybirds before and after the arrival of Harmonia axyridis, a globally rapidly expanding IAS. Location: Europe Methods: We used generalized linear mixed-effects models (GLMMs) to assess the distribution trends of eight conspicuous and historically widespread and common species of ladybird within Belgium and Britain before and after the arrival of H. axyridis. The distribution data were collated largely through public participatory surveys but verified by a recognized expert. We also used GLMMs to model trends in the abundance of ladybirds using data collated through systematic surveys of deciduous trees in Belgium, Britain and Switzerland. Results: Five (Belgium) and seven (Britain) of eight species studied show substantial declines attributable to the arrival of H. axyridis. Indeed, the two-spot ladybird, Adalia bipunctata, declined by 30% (Belgium) and 44% (Britain) over 5 years after the arrival of H. axyridis. Trends in ladybird abundance revealed similar patterns of declines across three countries. Main conclusion: Together, these analyses show H. axyridis to be displacing native ladybirds with high niche overlap, probably through predation and competition. This finding provides strong evidence of a causal link between the arrival of an IAS and decline in native biodiversity. Rapid biotic homogenization at the continental scale could impact on the resilience of ecosystems and severely diminish the services they deliver.
EFSA was asked for a partial risk assessment of Spodoptera frugiperda for the territory of the EU focussing on the main pathways for entry, factors affecting establishment, risk reduction options and ...pest management. As a polyphagous pest, five commodity pathways were examined in detail. Aggregating across these and other pathways, we estimate that tens of thousands to over a million individual larvae could enter the EU annually on host commodities. Instigating risk reduction options on sweetcorn, a principal host, reduces entry on that pathway 100‐fold. However, sweetcorn imports are a small proportion of all S. frugiperda host imports, several of which are already regulated and further regulation is estimated to reduce the median number entering over all pathways by approximately 10%. Low temperatures limit the area for establishment but small areas of Spain, Italy and Greece can provide climatic conditions suitable for establishment. If infested imported commodities are distributed across the EU in proportion to consumer population, a few hundreds to a few thousands of individuals would reach NUTS 2 regions within which suitable conditions for establishment exist. Although S. frugiperda is a known migrant, entry directly into the EU from extant populations in sub‐Saharan Africa is judged not feasible. However, if S. frugiperda were to establish in North Africa, in the range of thousands to over two million adults could seasonally migrate into the southern EU. Entry into suitable NUTS2 areas via migration will be greater than via commercial trade but is contingent on the establishment of S. frugiperda in North Africa. The likelihood of entry of the pest via natural dispersal could only be mitigated via control of the pest in Africa. If S. frugiperda were to arrive and become a pest of maize in the EU, Integrated Pest Management (IPM) or broad spectrum insecticides currently used against existing pests could be applied.
Evidence suggests a role for excessive inflammation in COVID-19 complications. Colchicine is an oral anti-inflammatory medication beneficial in gout, pericarditis, and coronary disease. We aimed to ...investigate the effect of colchicine on the composite of COVID-19-related death or hospital admission.
The present study is a phase 3, randomised, double-blind, adaptive, placebo-controlled, multicentre trial. The study was done in Brazil, Canada, Greece, South Africa, Spain, and the USA, and was led by the Montreal Heart Institute. Patients with COVID-19 diagnosed by PCR testing or clinical criteria who were not being treated in hospital were eligible if they were at least 40 years old and had at least one high-risk characteristic. The randomisation list was computer-generated by an unmasked biostatistician, and masked randomisation was centralised and done electronically through an automated interactive web-response system. The allocation sequence was unstratified and used a 1:1 ratio with a blocking schema and block sizes of six. Patients were randomly assigned to receive orally administered colchicine (0·5 mg twice per day for 3 days and then once per day for 27 days thereafter) or matching placebo. The primary efficacy endpoint was the composite of death or hospital admission for COVID-19. Vital status at the end of the study was available for 97·9% of patients. The analyses were done according to the intention-to-treat principle. The COLCORONA trial is registered with ClinicalTrials.gov (NCT04322682) and is now closed to new participants.
Trial enrolment began in March 23, 2020, and was completed in Dec 22, 2020. A total of 4488 patients (53·9% women; median age 54·0 years, IQR 47·0–61·0) were enrolled and 2235 patients were randomly assigned to colchicine and 2253 to placebo. The primary endpoint occurred in 104 (4·7%) of 2235 patients in the colchicine group and 131 (5·8%) of 2253 patients in the placebo group (odds ratio OR 0·79, 95·1% CI 0·61–1·03; p=0·081). Among the 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 96 (4·6%) of 2075 patients in the colchicine group and 126 (6·0%) of 2084 patients in the placebo group (OR 0·75, 0·57–0·99; p=0·042). Serious adverse events were reported in 108 (4·9%) of 2195 patients in the colchicine group and 139 (6·3%) of 2217 patients in the placebo group (p=0·051); pneumonia occurred in 63 (2·9%) of 2195 patients in the colchicine group and 92 (4·1%) of 2217 patients in the placebo group (p=0·021). Diarrhoea was reported in 300 (13·7%) of 2195 patients in the colchicine group and 161 (7·3%) of 2217 patients in the placebo group (p<0·0001).
In community-treated patients including those without a mandatory diagnostic test, the effect of colchicine on COVID-19-related clinical events was not statistically significant. Among patients with PCR-confirmed COVID-19, colchicine led to a lower rate of the composite of death or hospital admission than placebo. Given the absence of orally administered therapies to prevent COVID-19 complications in community-treated patients and the benefit of colchicine in patients with PCR-proven COVID-19, this safe and inexpensive anti-inflammatory agent could be considered for use in those at risk of complications. Notwithstanding these considerations, replication in other studies of PCR-positive community-treated patients is recommended.
The Government of Quebec, the Bill & Melinda Gates Foundation, the National Heart, Lung, and Blood Institute of the US National Institutes of Health, the Montreal Heart Institute Foundation, the NYU Grossman School of Medicine, the Rudin Family Foundation, and philanthropist Sophie Desmarais.
In recent decades we have seen rapid and co‐occurring changes in landscape structure, species distributions and even climate as consequences of human activity. Such changes affect the dynamics of the ...interaction between major forest pest species, such as bark beetles (Coleoptera: Curculionidae, Scolytinae), and their host trees. Normally breeding mostly in broken or severely stressed spruce; at high population densities some bark beetle species can colonise and kill healthy trees on scales ranging from single trees in a stand to multi‐annual landscape‐wide outbreaks. In Eurasia, the largest outbreaks are caused by the spruce bark beetle, Ips typographus (Linnaeus), which is common and shares a wide distribution with its main host, Norway spruce (Picea abies Karst.). A large literature is now available, from which this review aims to synthesize research relevant for the population dynamics of I. typographus and co‐occurring species under changing conditions.
We find that spruce bark beetle population dynamics tend to be metastable, but that mixed‐species and age‐heterogeneous forests with good site‐matching tend to be less susceptible to large‐scale outbreaks. While large accumulations of logs should be removed and/or debarked before the next swarming period, intensive removal of all coarse dead wood may be counterproductive, as it reduces the diversity of predators that in some areas may play a role in keeping I. typographus populations below the outbreak threshold, and sanitary logging frequently causes edge effects and root damage, reducing the resistance of remaining trees. It is very hard to predict the outcome of interspecific interactions due to invading beetle species or I. typographus establishing outside its current range, as they can be of varying sign and strength and may fluctuate depending on environmental factors and population phase. Most research indicates that beetle outbreaks will increase in frequency and magnitude as temperature, wind speed and precipitation variability increases, and that mitigating forestry practices should be adopted as soon as possible considering the time lags involved.
Context:
Little is known about the long-term health of subjects treated with GH in childhood, and Safety and Appropriateness of Growth hormone treatments in Europe (SAGhE) is a study addressing this ...question.
Objective:
The objective of the study was to evaluate the long-term mortality of patients treated with recombinant GH in childhood in France.
Design:
This was a population-based cohort study.
Setting:
The setting of the study was a French population-based register.
Participants:
A total of 6928 children with idiopathic isolated GH deficiency (n = 5162), neurosecretory dysfunction (n = 534), idiopathic short stature (n = 871), or born short for gestational age (n = 335) who started treatment between 1985 and 1996 participated in the study. Follow-up data on vital status were available in September 2009 for 94.7% of the patients.
Main outcome measures:
All-cause and cause-specific mortality was measured in the study.
Results:
All-cause mortality was increased in treated subjects standardized mortality ratio (SMR) 1.33, 95% confidence interval (CI) 1.08–1.64. In a multivariate analysis adjusted for height, the use of GH doses greater than 50 μg/kg · d was associated with mortality rates using external and internal references (SMR 2.94, 95% CI 1.22–7.07, hazard ratio 2.79, 95% CI 1.14–6.82). All type cancer-related mortality was not increased. Bone tumor-related mortality was increased (SMR 5.00, 95% CI 1.01–14.63). An increase in mortality due to diseases of the circulatory system (SMR 3.07, 95% CI 1.40–5.83) or subarachnoid or intracerebral hemorrhage (SMR 6.66, 95% CI 1.79–17.05) was observed.
Conclusions:
Mortality rates were increased in this population of adults treated as children with recombinant GH, particularly in those who had received the highest doses. Specific effects were detected in terms of death due to bone tumors or cerebral hemorrhage but not for all cancers. These results highlight the need for additional studies of long-term mortality and morbidity after GH treatment in childhood.
Scolytinae is a subfamily of weevils that contains many major pest species. Most scolytines employ an outbreeding mating system: individuals emerge from their natal host trees and fly to new hosts, ...where they mate with unrelated conspecifics. However, in several outbreeding species, some individuals mate prior to emergence, either with a sibling or an unrelated neighbor from another gallery. Preemergence mating allows females to start adult life with a supply of sperm; they can then dig a gallery on their own in a new host tree. In this study, we examined preemergence mating in
Ips typographus
, a supposedly outbred bark beetle that causes considerable damage to European spruce forests. Our field and laboratory studies have shown that 15–94% of females are mated at (re)emergence, a wide range of values that is shaped by environmental conditions and time of year. This figure is also positively correlated with time spent under the bark. Moreover, in laboratory experiments, outbreeding females had the same level of productivity whether they established themselves with a partner or on their own. However, compared to both types of outbreeding females, solitary inbreeding females exhibited lower productivity due to higher mortality in the egg and postlarval stages, suggesting the presence of inbreeding depression. In a choice experiment, females preferentially entered nuptial chambers containing unrelated males versus brothers. These results shed new light on this bark beetle’s mating behavior, which ultimately influences the species’ ability to colonize new areas.
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