Association is not causation: treatment effects cannot be estimated from observational data in heart failure

Aims: Treatment ‘effects’ are often inferred from non-randomized and observational studies. These studies have inherent biases and limitations, which may make therapeutic inferences based on their results unreliable. We compared the conflicting findings of these studies to those of prospective randomized controlled trials (RCTs) in relation to pharmacological treatments for heart failure (HF). Methods and results: We searched Medline and Embase to identify studies of the association between non-randomized drug therapy and all-cause mortality in patients with HF until 31 December 2017. The treatments of interest were: angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, mineralocorticoid receptor antagonists (MRAs), statins, and digoxin. We compared the findings of these observational studies with those of relevant RCTs. We identified 92 publications, reporting 94 non-randomized studies, describing 158 estimates of the ‘effect’ of the six treatments of interest on all-cause mortality, i.e. some studies examined more than one treatment and/or HF phenotype. These six treatments had been tested in 25 RCTs. For example, two pivotal RCTs showed that MRAs reduced mortality in patients with HF with reduced ejection fraction. However, only one of 12 non-randomized studies found that MRAs were of benefit, with 10 finding a neutral effect, and one a harmful effect. Conclusion: This comprehensive comparison of studies of non-randomized data with the findings of RCTs in HF shows that it is not possible to make reliable therapeutic inferences from observational associations. While trials undoubtedly leave gaps in evidence and enrol selected participants, they clearly remain the best guide to the treatment of patients

Are long term care facilities (LTCF) prepared for H1N1?

Background: A 2007 survey of Midwestern LTCF suggested that less than 25% had a written pandemic influenza response plan. Upon request from a rural nursing home, we developed pandemic influenza planning recommendations for LTCF. Methods: In September 2009, we mailed written recommendations to 144 LTCF in West Texas and New Mexico and included a survey with questions about the facility, facility preparedness, and the usefulness of the recommendations. We performed standard statistical analysis on returned surveys. Results: 24/143 (17%) facilities returned the survey, indicating that they had read (21) or planned to read (3) the recommendations. 15/23 (65%) of surveys were from facilities in rural communities. 16/23 (70%) of facilities already had a written pandemic influenza response plan. Most facilities had stockpiled some supplies: gloves (19/24, 79%), alcohol based hand washes (18/24, 75%), surgical masks (16/24, 67%), and N95 masks (8/24, 33%). 18/24 (75%) had discussed obtaining vaccine with the health department, 17/24 (71%) had instituted staff education and training, and 15/24 (63%) had developed written material for staff and families. 11/24 (49%) anticipated staffing shortages; most planned to use overtime, non-clinical staff, and volunteers to provide for clinical services during staff shortages. Only 3/24 (13%) of these facilities planned to use commercial agencies for staffing shortage. Of those who had read the recommendations, 100% found them helpful or very helpful. The most frequently cited anticipated changes based on the recommendations included changing isolation procedures (11/24, 46%) and vaccination program (9/24, 38%); review of staff absenteeism policies (38%); and revision of the written pandemic influenza plan (38%). There were no statistical differences between facilities in urban and rural communities with regard to the presence of a written plan, staff training, discussions with the health department, stockpiling of supplies, or anticipated changes based on review of the recommendations. Conclusions: This small survey suggests that LTCF may be better prepared for pandemic influenza than they were two years ago. These facilities found that mailed written planning recommendations were helpful, and would result in changes to deal with H1N1 pandemic influenza

Nitric oxide and coronary vascular endothelium adaptations in hypertension

This review highlights a number of nitric oxide (NO)-related mechanisms that contribute to coronary vascular function and that are likely affected by hypertension and thus become important clinically as potential considerations in prevention, diagnosis, and treatment of coronary complications of hypertension. Coronary vascular resistance is elevated in hypertension in part due to impaired endothelium-dependent function of coronary arteries. Several lines of evidence suggest that other NO synthase isoforms and dilators other than NO may compensate for impairments in endothelial NO synthase (eNOS) to protect coronary artery function, and that NO-dependent function of coronary blood vessels depends on the position of the vessel in the vascular tree. Adaptations in NOS isoforms in the coronary circulation to hypertension are not well described so the compensatory relationship between these and eNOS in hypertensive vessels is not clear. It is important to understand potential functional consequences of these adaptations as they will impact the efficacy of treatments designed to control hypertension and coronary vascular disease. Polymorphisms of the eNOS gene result in significant associations with incidence of hypertension, although mechanistic details linking the polymorphisms with alterations in coronary vasomotor responses and adaptations to hypertension are not established. This understanding should be developed in order to better predict those individuals at the highest risk for coronary vascular complications of hypertension. Greater endothelium-dependent dilation observed in female coronary arteries is likely related to endothelial Ca2+ control and eNOS expression and activity. In hypertension models, the coronary vasculature has not been studied extensively to establish mechanisms for sex differences in NO-dependent function. Genomic and nongenomic effects of estrogen on eNOS and direct and indirect antioxidant activities of estrogen are discussed as potential mechanisms of interest in coronary circulation that could have implications for sex- and estrogen status-dependent therapy for hypertension and coronary dysfunction. The current review identifies some important basic knowledge gaps and speculates on the potential clinical relevance of hypertension adaptations in factors regulating coronary NO function

Project Energize: intervention development and 10 years of progress in preventing childhood obesity

Prevention of childhood obesity is a global priority. The school setting offers access to large numbers of children and the ability to provide supportive environments for quality physical activity and nutrition. This article describes Project Energize, a through-school physical activity and nutrition programme that celebrated its 10-year anniversary in 2015 so that it might serve as a model for similar practices, initiatives and policies elsewhere. The programme was envisaged and financed by the Waikato District Health Board of New Zealand in 2004 and delivered by Sport Waikato to 124 primary schools as a randomised controlled trial from 2005 to 2006. The programme has since expanded to include all 242 primary schools in the Waikato region and 70 schools in other regions, including 53,000 children. Ongoing evaluation and development of Project Energize has shown it to be sustainable (ongoing for >10 years), both effective (lower obesity, higher physical fitness) and cost effective (one health related cost quality adjusted life year between $18,000 and$30,000) and efficient ($45/child/year) as a childhood 'health' programme. The programme's unique community-based approach is inclusive of all children, serving a population that is 42 % Ma¯ori, the indigenous people of New Zealand. While the original nine healthy eating and seven quality physical activity goals have not changed, the delivery and assessment processes has been refined and the health service adapted over the 10 years of the programme existence, as well as adapted over time to other settings including early childhood education and schools in Cork in Ireland. Evaluation and research associated with the programme delivery and outcomes are ongoing. The dissemination of findings to politicians and collaboration with other service providers are both regarded as priorities

Corrosion and Passivation of Fe and FeN Films

The role of nitrogen in corrosion and passivation of thin Fe-N films was studied. Sputtered films with different levels of nitrogen were characterized for composition, conductivity, stress, and crystallinity. Corrosion and passivation of the films were evaluated by electrochemical measurements combined with in situ ellipsometry and ex situ x-ray photoelectron spectroscopy. The results indicate that in deaerated solutions the primary action of N is to reduce the catalytic activity of the surface for the hydrogen reaction and thereby reduce corrosion. In aerated solutions the corrosion rate increases with N content. Kinetics of the protective oxide formation as a function of potential, percent N, and the presence of borate buffer are discussed in detail. The work is relevant to the behavior of oxide-free Fe-N surfaces in contact with mild, nearly neutral electrolytes, such as could be used in fabrication of magnetic recording heads

Quantification of ethyl acetate using FAIMS

The enjoyment of wine is based not only on its flavour but also its aroma. The presence of compounds, such as ethyl acetate, can add a desirable depth of body, richness and sweetness to a wine. However, if the levels exceed the human perception threshold (100 - 200 mg/l) an aroma similar to acetone becomes prevalent and the wine is regarded as spoilt.A study was undertaken to determine the concentration of ethyl acetate within wine using a Gas Chromatograph coupled with Field Asymmetric Ion Mobility Spectrometry (FAIMS). The use of FAIMS (also known as Differential Mobility Spectrometry) as a selective detector has increasingly become prevalent within analytical science. There is now a vibrant community of researchers working with the technique and different commercial systems are readily available. Two such systems are the Tourist and Lonestar instruments available from Owlstone Ltd. The Owlstone systems are characterised by the sensor being a solid state device, which imposes constraints on operational parameters but also offers opportunities over comparable devices. FAIMS technology requires the interaction of compounds both within the ionisation and separation region. To influence the interactions in these two regions studies were completed at elevated (compared to ambient) pressures and humidity. The study of ethyl acetate within wine provided an opportunity to investigate these effects and also provided a route for optimisation of the instrument for the study. It was found, in contrast to a previously reported investigation, that increasing the pressure resulted in a greater resolution of compounds. A more complicated relationship was observed with respect to humidity, believed attributable to water being an important constituent of reactive and product ion formation. Additional effects due to the presence of co-solvents were observed and subsequently managed so as to provide increased sensitivity. The quantification of ethyl acetate within wine was accomplished considerably below the human perception threshold providing the opportunity to better manage this multifarious compound throughout manufacture and the product lifecycle

Anti–Vascular Endothelial Growth Factor Drugs Compared With Panretinal Photocoagulation for the Treatment of Proliferative Diabetic Retinopathy: A Cost-Effectiveness Analysis

\ua9 2024Objectives: This study aimed to evaluate the cost-effectiveness of anti–vascular endothelial growth factor drugs (anti-VEGFs) compared with panretinal photocoagulation (PRP) for treating proliferative diabetic retinopathy (PDR) in the United Kingdom. Methods: A discrete event simulation model was developed, informed by individual participant data meta-analysis. The model captures treatment effects on best corrected visual acuity in both eyes, and the occurrence of diabetic macular edema and vitreous hemorrhage. The model also estimates the value of undertaking further research to resolve decision uncertainty. Results: Anti-VEGFs are unlikely to generate clinically meaningful benefits over PRP. The model predicted anti-VEGFs be more costly and similarly effective as PRP, generating 0.029 fewer quality-adjusted life-years at an additional cost of \ua33688, with a net health benefit of −0.214 at a \ua320 000 willingness-to-pay threshold. Scenario analysis results suggest that only under very select conditions may anti-VEGFs offer potential for cost-effective treatment of PDR. The consequences of loss to follow-up were an important driver of model outcomes. Conclusions: Anti-VEGFs are unlikely to be a cost-effective treatment for early PDR compared with PRP. Anti-VEGFs are generally associated with higher costs and similar health outcomes across various scenarios. Although anti-VEGFs were associated with lower diabetic macular edema rates, the number of cases avoided is insufficient to offset the additional treatment costs. Key uncertainties relate to the long-term comparative effectiveness of anti-VEGFs, particularly considering the real-world rates and consequences of treatment nonadherence. Further research on long-term visual acuity and rates of vision-threatening complications may be beneficial in resolving uncertainties

'This is what democracy looks like' : New Labour's blind spot and peripheral vision

New Labour in government since 1997 has been roundly criticized for not possessing a clear, coherent and consistent democratic vision. The absence of such a grand vision has resulted, from this critical perspective, in an absence of 'joined-up' thinking about democracy in an evolving multi-level state. Tensions have been all too apparent between the government's desire to exert central direction - manifested in its most pathological form as 'control freakery' - and its democratising initiatives derived from 'third-way' obsessions with 'decentralising', 'empowering' and 'enabling'. The purpose of this article is to examine why New Labour displayed such apparently impaired democratic vision and why it appeared incapable of conceiving of democratic reform 'in the round'. This article seeks to explain these apparent paradoxes, however, through utilising the notion of 'macular degeneration'. In this analysis, the perceived democratic blind spot of New Labour at Westminster is connected to a democratic peripheral vision, which has envisaged innovative participatory and decentred initiatives in governance beyond Westminster