Costs of switching to low global warming potential inhalers. An economic and carbon footprint analysis of NHS prescription data in England.

OBJECTIVES: Metered-dose inhalers (MDIs) contain propellants which are potent greenhouse gases. Many agencies propose a switch to alternative, low global warming potential (GWP) inhalers, such as dry powder inhalers (DPIs). We aimed to analyse the impact on greenhouse gas emissions and drug costs of making this switch. SETTING: We studied National Health Service prescription data from England in 2017 and collated carbon footprint data on inhalers commonly used in England. DESIGN: Inhalers were separated into different categories according to their mechanisms of action (eg, short-acting beta-agonist). Within each category we identified low and high GWP inhalers and calculated the cost and carbon impact of changing to low GWP inhalers. We modelled scenarios for swapping proportionally according to the current market share of each equivalent DPI (model 1) and switching to the lowest cost pharmaceutically equivalent DPI (model 2). We also reviewed available data on the carbon footprint of inhalers from scientific publications, independently certified reports and patents to provide more accurate carbon footprint information on different types of inhalers. RESULTS: If MDIs using HFA propellant are replaced with the cheapest equivalent DPI, then for every 10% of MDIs changed to DPIs, drug costs decrease by £8.2M annually. However if the brands of DPIs stay the same as 2017 prescribing patterns, for every 10% of MDIs changed to DPIs, drug costs increase by £12.7M annually. Most potential savings are due to less expensive long-acting beta-agonist (LABA)/inhaled corticosteroids (ICS) inhalers. Some reliever inhalers (eg, Ventolin) have a carbon footprint over 25 kg CO2e per inhaler, while others use far less 1,1,1,2-tetrafluoroethane (HFA134a) (eg, Salamol) with a carbon footprint of <10 kg CO2e per inhaler. 1,1,1,2,3,3,3-Heptafluoropropane (HFA227ea) LABA/ICS inhalers (eg, Flutiform) have a carbon footprint over 36 kg CO2e, compared with an equivalent HFA134a combination inhaler (eg, Fostair) at <20 kg CO2e. For every 10% of MDIs changed to DPIs, 58 kt CO2e could be saved annually in England. CONCLUSIONS: Switching to DPIs would result in large carbon savings and can be achieved alongside reduced drug costs by using less expensive brands. Substantial carbon savings can be made by using small volume HFA134a MDIs, in preference to large volume HFA134a MDIs, or those containing HFA227ea as a propellant.This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors

The inter-relationship of symptom severity and quality of life in 2055 patients with primary biliary cholangitis

BackgroundAge at presentation with primary biliary cholangitis (PBC) is associated with differ-ential response to ursodeoxycholic acid (UDCA) therapy. Younger-presentingpatients are less likely to respond to treatment and more likely to need transplantor die from the disease. PBC has a complex impact on quality of life (QoL), withsystemic symptoms often having significant impact.AimTo explain the impact of age at presentation on perceived QoL and the inter-related symptoms which impact upon it.MethodsUsing the UK-PBC cohort, symptoms were assessed using the PBC-40 and othervalidated tools. Data were available on 2055 patients.ResultsOf the 1990 patients reporting a global PBC-QoL score, 66% reported good/neutralscores and 34% reported poor scores. Each 10-year increase in age at presentationwas associated with a 14% decrease in risk of poor perceived QoL (OR = 0.86,95% CI: 0.75–0.98, P &lt; 0.05). All sympto m domains were similarly age-associated(P &lt; 0.01). Social dysfunction was the symptom factor with the greatest impa ct onQoL. Median (interquartile range) PBC-40 social scores for patient s with good per-ceived QoL were 18 (14–23) compared with 34 (29–39) for those with poor QoL.ConclusionThe majo rity of patients with primary biliary cholangitis do not feel their QoL isimpaired, although impairment is reported by a sizeable minority. Age at presenta-tion is associated with impact on per ceived QoL and the symptoms impairing it,with younger patients being more affected. Social dysfunction makes the greatestcontribution to QoL impairment, and it should be targeted in trials aimed atimproving life quality

The inter-relationship of symptom severity and quality of life in 2055 patients with primary biliary cholangitis.

BACKGROUND: Age at presentation with primary biliary cholangitis (PBC) is associated with differential response to ursodeoxycholic acid (UDCA) therapy. Younger-presenting patients are less likely to respond to treatment and more likely to need transplant or die from the disease. PBC has a complex impact on quality of life (QoL), with systemic symptoms often having significant impact. AIM: To explain the impact of age at presentation on perceived QoL and the inter-related symptoms which impact upon it. METHODS: Using the UK-PBC cohort, symptoms were assessed using the PBC-40 and other validated tools. Data were available on 2055 patients. RESULTS: Of the 1990 patients reporting a global PBC-QoL score, 66% reported good/neutral scores and 34% reported poor scores. Each 10-year increase in age at presentation was associated with a 14% decrease in risk of poor perceived QoL (OR = 0.86, 95% CI: 0.75-0.98, P < 0.05). All symptom domains were similarly age-associated (P < 0.01). Social dysfunction was the symptom factor with the greatest impact on QoL. Median (interquartile range) PBC-40 social scores for patients with good perceived QoL were 18 (14-23) compared with 34 (29-39) for those with poor QoL. CONCLUSION: The majority of patients with primary biliary cholangitis do not feel their QoL is impaired, although impairment is reported by a sizeable minority. Age at presentation is associated with impact on perceived QoL and the symptoms impairing it, with younger patients being more affected. Social dysfunction makes the greatest contribution to QoL impairment, and it should be targeted in trials aimed at improving life quality

Intraspecific Diversity Regulates Fungal Productivity and Respiration

Individuals and not just species are key components of biodiversity, yet the relationship between intraspecific diversity and ecosystem functioning in microbial systems remains largely untested. This limits our ability to understand and predict the effects of altered genetic diversity in regulating key ecosystem processes and functions. Here, we use a model fungal system to test the hypothesis that intraspecific genotypic richness of Paxillus obscurosporus stimulates biomass and CO2 efflux, but that this is dependent on nitrogen supply. Using controlled experimental microcosms, we show that populations containing several genotypes (maximum 8) of the fungus had greater productivity and produced significantly more CO2 than those with fewer genotypes. Moreover, intraspecific diversity had a much stronger effect than a four-fold manipulation of the carbon:nitrogen ratio of the growth medium. The effects of intraspecific diversity were underpinned by strong roles of individuals, but overall intraspecific diversity increased the propensity of populations to over-yield, indicating that both complementarity and selection effects can operate within species. Our data demonstrate the importance of intraspecific diversity over a range of nitrogen concentrations, and the need to consider fine scale phylogenetic information of microbial communities in understanding their contribution to ecosystem processes

Health status in the ambulance services: a systematic review

BACKGROUND: Researchers have become increasingly aware that ambulance personnel may be at risk of developing work-related health problems. This article systematically explores the literature on health problems and work-related and individual health predictors in the ambulance services. METHODS: We identified the relevant empirical literature by searching several electronic databases including Medline, EMBASE, PsychINFO, CINAHL, and ISI Web of Science. Other relevant sources were identified through reference lists and other relevant studies known by the research group. RESULTS: Forty-nine studies are included in this review. Our analysis shows that ambulance workers have a higher standardized mortality rate, higher level of fatal accidents, higher level of accident injuries and a higher standardized early retirement on medical grounds than the general working population and workers in other health occupations. Ambulance workers also seem to have more musculoskeletal problems than the general population. These conclusions are preliminary at present because each is based on a single study. More studies have addressed mental health problems. The prevalence of post-traumatic stress symptom caseness was > 20% in five of seven studies, and similarly high prevalence rates were reported for anxiety and general psychopathology in four of five studies. However, it is unclear whether ambulance personnel suffer from more mental health problems than the general working population. CONCLUSION: Several indicators suggest that workers in the ambulance services experience more health problems than the general working population and workers in other health occupations. Several methodological challenges, such as small sample sizes, non-representative samples, and lack of comparisons with normative data limit the interpretation of many studies. More coordinated research and replication are needed to compare data across studies. We discuss some strategies for future research

A method of determining where to target surveillance efforts in heterogeneous epidemiological systems

The spread of pathogens into new environments poses a considerable threat to human, animal, and plant health, and by extension, human and animal wellbeing, ecosystem function, and agricultural productivity, worldwide. Early detection through effective surveillance is a key strategy to reduce the risk of their establishment. Whilst it is well established that statistical and economic considerations are of vital importance when planning surveillance efforts, it is also important to consider epidemiological characteristics of the pathogen in question—including heterogeneities within the epidemiological system itself. One of the most pronounced realisations of this heterogeneity is seen in the case of vector-borne pathogens, which spread between ‘hosts’ and ‘vectors’—with each group possessing distinct epidemiological characteristics. As a result, an important question when planning surveillance for emerging vector-borne pathogens is where to place sampling resources in order to detect the pathogen as early as possible. We answer this question by developing a statistical function which describes the probability distributions of the prevalences of infection at first detection in both hosts and vectors. We also show how this method can be adapted in order to maximise the probability of early detection of an emerging pathogen within imposed sample size and/or cost constraints, and demonstrate its application using two simple models of vector-borne citrus pathogens. Under the assumption of a linear cost function, we find that sampling costs are generally minimised when either hosts or vectors, but not both, are sampled

Precise determination of the mass of the Higgs boson and tests of compatibility of its couplings with the standard model predictions using proton collisions at 7 and 8 TeV

Peer reviewe

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Search for dark matter produced in association with a single top quark or a top quark pair in proton-proton collisions at s=13 TeV

A search has been performed for heavy resonances decaying to ZZ or ZW in 2l2q final states, with two charged leptons (l = e, mu) produced by the decay of a Z boson, and two quarks produced by the decay of a W or Z boson. The analysis is sensitive to resonances with masses in the range from 400 to 4500 GeV. Two categories are defined based on the merged or resolved reconstruction of the hadronically decaying vector boson, optimized for high- and low-mass resonances, respectively. The search is based on data collected during 2016 by the CMS experiment at the LHC in proton-proton collisions with a center-of-mass energy of root s = 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1). No excess is observed in the data above the standard model background expectation. Upper limits on the production cross section of heavy, narrow spin-1 and spin-2 resonances are derived as a function of the resonance mass, and exclusion limits on the production of W' bosons and bulk graviton particles are calculated in the framework of the heavy vector triplet model and warped extra dimensions, respectively.A search has been performed for heavy resonances decaying to ZZ or ZW in 2l2q final states, with two charged leptons (l = e, mu) produced by the decay of a Z boson, and two quarks produced by the decay of a W or Z boson. The analysis is sensitive to resonances with masses in the range from 400 to 4500 GeV. Two categories are defined based on the merged or resolved reconstruction of the hadronically decaying vector boson, optimized for high- and low-mass resonances, respectively. The search is based on data collected during 2016 by the CMS experiment at the LHC in proton-proton collisions with a center-of-mass energy of root s = 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1). No excess is observed in the data above the standard model background expectation. Upper limits on the production cross section of heavy, narrow spin-1 and spin-2 resonances are derived as a function of the resonance mass, and exclusion limits on the production of W' bosons and bulk graviton particles are calculated in the framework of the heavy vector triplet model and warped extra dimensions, respectively.A search for dark matter produced in association with top quarks in proton-proton collisions at a center-of-mass energy of 13 TeV is presented. The data set used corresponds to an integrated luminosity of 35.9 fb(-1) recorded with the CMS detector at the LHC. Whereas previous searches for neutral scalar or pseudoscalar mediators considered dark matter production in association with a top quark pair only, this analysis also includes production modes with a single top quark. The results are derived from the combination of multiple selection categories that are defined to target either the single top quark or the top quark pair signature. No significant deviations with respect to the standard model predictions are observed. The results are interpreted in the context of a simplified model in which a scalar or pseudoscalar mediator particle couples to a top quark and subsequently decays into dark matter particles. Scalar and pseudoscalar mediator particles with masses below 290 and 300 GeV, respectively, are excluded at 95% confidence level, assuming a dark matter particle mass of 1 GeV and mediator couplings to fermions and dark matter particles equal to unity.Peer reviewe