Potential Consequences In Terms Research Articles

Restoration of hip anatomy using computer modelling prior to total hip arthroplasty and its potential consequences in terms of lower limb-length difference.

Restoring hip anatomy during total hip arthroplasty (THA) is the gold standard. The general goal is for hips to be symmetrical in terms of height. This study aimed to analyse the effect of simulating hip length (HL) equalisation on leg-length difference (LLD) before and after THA with a computerised plan. 141 consecutive patients were enrolled following THA. Outcomes of interest were preoperative hip-length difference (HLD) and LLD as determined on CT and final LLD as determined by simulating HL equalisation. We divided patients into 3 groups: no LLD, LLD >5 mm and LLD ⩾10 mm. The rate of preoperative LLD >5 mm and LLD ⩾10 mm was 37.5% and 14.8%, respectively. HL equalisation did not change LLD distribution in the overall cohort. Among patients with smaller preoperative HLs and LLDs, HL equalisation changed the rate of LLD >5 mm from 100% (n = 24) to 41.7% (n = 10) (p < 0.0001) and of LLD ⩾10 mm from 100% (n = 12) to 16.7% (n = 2) (p < 0.0001). Among patients with no preoperative LLD, HL equalisation changed the rate of LLD ⩽5 mm from 100% (n = 64) to 59.3% (n = 38) (p < 0.0001) and of LLD<10 mm from 100% (n = 76) to 89.5% (n = 68) (p = 0.006). Restoring biomechanical hip anatomy by HL equalisation may not be the correct goal for all patients. In patients with no LLD and shorter HLs, equalisation could result in LLD >5 mm in 40% of patients and LLD >10 mm in 10%, demonstrating the necessity to further analyse individuals and propose a personalised stem position.

Integrating statistical and visual analytic methods for bot identification of health-related survey data

ObjectiveIn recent years, we have increasingly observed issues concerning quality of online information due to misinformation and disinformation. Aside from social media, there is growing awareness that questionnaire data collected using online recruitment methods may include suspect data provided by bots. Issues with data quality can be particularly problematic in health and/or biomedical contexts; thus, developing robust methods for suspect data identification and removal is of paramount importance in informatics. In this study, we describe an interactive visual analytics approach to suspect data identification and removal and demonstrate the application of this approach on questionnaire data pertaining to COVID-19 derived from different recruitment venues, including listservs and social media. MethodsWe developed a pipeline for data cleaning, pre-processing, analysis, and automated ranking of data to address data quality issues. We then employed the ranking in conjunction with manual review to identify suspect data and remove them from subsequent analyses. Last, we compared differences in the data before and after removal. ResultsWe performed data cleaning, pre-processing, and exploratory analysis on a survey dataset (N = 4,163) collected using multiple recruitment mechanins using the Qualtrics survey platform. Based on these results, we identified suspect features and used these to generate a suspect feature indicator for each survey response. We excluded survey responses that did not fit the inclusion criteria for the study (n = 29) and then performed manual review of the remaining responses, triangulating with the suspect feature indicator. Based on this review, we excluded 2,921 responses. Additional responses were excluded based on a spam classification by Qualtrics (n=13), and the percentage of survey completion (n=328), resulting in a final sample size of 872. We performed additional analyses to demonstrate the extent to which the suspect feature indicator was congruent with eventual inclusion, as well as compared the characteristics of the included and excluded data. ConclusionOur main contributions are: 1) a proposed framework for data quality assessment, including suspect data identification and removal; 2) the analysis of potential consequences in terms of representation bias in the dataset; and 3) recommendations for implementation of this approach in practice.

Enabling Long-term Predictions and Cost-benefit Analysis Related to Housing Adaptation Needs for a Population Aging in Place: Protocol for a Simulation Study.

BackgroundPolicies that promote aging in place are common in Sweden and many other countries. However, the current housing stock cannot sufficiently accommodate a population aging in place considering how functional capacity and housing needs change as people age. To be suitable for all regardless of their functional ability, housing should be designed or adapted to facilitate the performance of activities of daily living. Long-term planning and plausible projections of development 20 to 30 years into the future are needed.ObjectiveThe overall aim is to develop simulation models that enable long-term predictions and analysis of potential consequences in terms of societal gains and costs for different large-scale measures and interventions in the ordinary housing stock.MethodsThis study is designed as a simulation study and will broadly apply health impact assessment methods in collaboration with five municipalities in Sweden. Individual interviews and research circles were used to identify current and prioritize potential new policies to improve the accessibility of the housing stock. We will run a series of simulations based on an estimated willingness to pay from discussions with the municipalities. Two to three different prioritized policies will be compared simultaneously using Markov cohort analysis to estimate the potential costs and health impact on the population. Using data from a systematic review and existing population-based data sets with individual-level data on home and health variables, we will calculate parameter estimates for the relations between housing accessibility and health outcomes. The potential impact of selected policy interventions will be estimated in several microsimulations representing people living in the community. Sensitivity analyses will be conducted for each simulation.ResultsAs of April 2022, open access data was collected, and a systematic review was underway and expected to be completed by November 2022. Collaboration with five municipalities was established in autumn 2020. In spring 2021, the municipalities developed a list of prioritized policy interventions to be tested and used in the simulation models. Inventories of barrier frequencies in ordinary housing started in spring 2022 and are expected to be completed in autumn 2022. Data gathering and analyses for simulation inputs will be completed during 2022 followed by the simulation modeling analyses to be completed in 2023.ConclusionsImproved accessibility of the ordinary housing stock has the potential to maintain or improve the health of the aging population. This study will generate tools that enable long-term predictions and reliable cost-benefit estimates related to the housing adaptation needs for a population aging in place, thus providing support for the best-informed policy decisions.International Registered Report Identifier (IRRID)DERR1-10.2196/39032

Cancer-related mortality among people with intellectual disabilities: A nationwide population-based cohort study.

BackgroundConcerns have been raised about access to cancer screening and the timely receipt of cancer care for people with an intellectual disability (ID). However, knowledge about cancer mortality as a potential consequence of these disparities is still limited. This study, therefore, compared cancer‐related mortality patterns between people with and without ID.MethodsA historical cohort study (2015‐2019) linked the Dutch adult population (approximately 12 million people with an ID prevalence of 1.45%) and mortality registries. Cancer‐related mortality was identified by the underlying cause of death (according to the chapter on neoplasms in the International Classification of Diseases, Tenth Revision). Observed mortality and calculated age‐ and sex‐standardized mortality ratios (SMRs) with 95% confidence intervals (CIs) were reported.ResultsThere were 11,102 deaths in the ID population (21.7% cancer‐related; n = 2408) and 730,405 deaths in the general population (31.2%; n = 228,120) available for analysis. Cancer was noted as the cause of death more often among people with ID in comparison with the general population (SMR, 1.48; 95% CI, 1.42‐1.54), particularly in the young age groups. High‐mortality cancers included cancers within the national screening program (SMRs, 1.43‐1.94), digestive cancers (SMRs, 1.24‐2.56), bladder cancer (SMR, 2.07; 95% CI, 1.61‐2.54), and cancers of unknown primary (SMR, 2.48; 95% CI, 2.06‐2.89).ConclusionsCancer was reported as the cause of death approximately 1.5 times more often in people with ID compared with the general population. This mortality disparity may indicate adverse effects from inequalities in screening and cancer care experienced by people with ID.Lay Summary People with an intellectual disability (ID) may find it challenging to participate in cancer screening or to receive timely cancer care.To understand potential consequences in terms of mortality, this study compared cancer‐related mortality between people with and without ID in the Netherlands.Cancer was reported as the cause of death approximately 1.5 times more often among people with ID than others.Because large differences were found that were related to screening cancers and cancers for which the primary tumor was unknown, this study's results raise concerns about equality in screening practices and cancer care for people with ID.

Impairment of microbial and meiofaunal ecosystem functions linked to algal forest loss

Habitat loss is jeopardizing marine biodiversity. In the Mediterranean Sea, the algal forests of Cystoseira spp. form one of the most complex, productive and vulnerable shallow-water habitats. These forests are rapidly regressing with negative impact on the associated biodiversity, and potential consequences in terms of ecosystem functioning. Here, by comparing healthy Cystoseira forests and barren grounds (i.e., habitats where the macroalgal forests disappeared), we assessed the effects of habitat loss on meiofaunal and nematode biodiversity, and on some ecosystem functions (here measured in terms of prokaryotic and meiofaunal biomass). Overall, our results suggest that the loss of Cystoseira forests and the consequent barren formation is associated with the loss of meiofaunal higher taxa and a decrease of nematode biodiversity, leading to the collapse of the microbial and meiofaunal variables of ecosystem functions. We conclude that, given the very limited resilience of these ecosystems, active restoration of these vulnerable habitats is needed, in order to recover their biodiversity, ecosystem functions and associated services.

Impact of the COVID-19 Outbreak on the Management of Patients with Cancer.

The coronavirus SARS-CoV-2 (COVID-19) outbreak is having a profound impact on the management of patients with cancer. In this review, we comprehensively investigate the various aspects of cancer care during the pandemic, taking advantage of data generated in Asia and Europe at the frontline of the COVID-19 pandemic spread. Cancer wards have been subjected to several modifications to protect patients and healthcare professionals from COVID-19 infection, while attempting to maintain cancer diagnosis, therapy, and research. In this setting, the management of COVID-19 infected patients with cancer is particularly challenging. We also discuss the direct and potential remote impacts of the global pandemic on the mortality of patients with cancer. As such, the indirect impact of the pandemic on the global economy and the potential consequences in terms of cancer mortality are discussed. As the infection is spreading worldwide, we are obtaining more knowledge on the COVID-19 pandemic consequences that are currently impacting and may continue to further challenge cancer care in several countries.

Policy over- and under-design: an information quality perspective.

This article seeks to improve our understanding of what policy over- and under-design mean; what are the consequences of these suboptimal designs; and how politics matters to these designs. Based on the review of the literature and a variety of examples that focus on the role of information quality in policy design, and drawing on two phenomena from the field of epidemiology (namely, over-adjustment and unnecessary adjustment), the article enhances the definitional clarity of the terms under investigation and allows us to address the difficulty in reconciling technical problem solving with politics. The article proposes new definitional statements of proportionate and disproportionate policy designs that vary according to the extent to which the main design properties are adjusted to low-quality information. It also explores distinct variations in a few policy characteristics resulting from over- and under-design. The policy characteristics examined here include economic efficiency, policy effectiveness, policy robustness; the space for making significant changes at a later stage when high-quality information becomes available; the potential consequences in terms of policy over- and under-reaction; and the political ramifications of these suboptimal designs for elected executives. With regard to the interaction between technical and political logics, the article posits that deliberate policy over- and under-design can be viewed as solutions to serious political problems faced by elected executives, especially in politically sensitive times. Therefore, it facilitates a more realistic understanding of the conditions under which a policy is under- or over-designed to respond to some objectives but entirely proportionate with regard to others.

Potential Output, EU Fiscal Surveillance and the COVID-19 Shock

This paper discusses how the technical foundations of the EU’s fiscal rules constrain the fiscal space in EU countries in the context of the COVID-19 pandemic. We review the evidence on how estimates of potential output, which are at the heart of essential control indicators in EU fiscal surveillance, were revised in the ten years running up to the COVID-19 pandemic, and how these revisions affected the fiscal stance of EU countries. We provide first evidence for downward revisions in the European Commission’s potential output estimates against the background of the COVID-19 shock across the EU27 countries, and we assess the potential consequences in terms of fiscal space. According to our results, one additional percentage point in predicted losses of actual output is associated with a loss in potential output of about 0.6 percentage points. Given the importance of model-based estimates in the EU’s fiscal rules, avoiding pro-cyclical fiscal tightening will require that policymakers’ hands are not tied by overly pessimistic views on the development of potential output.

The Bird Strike Challenge

Collisions between birds and aircraft pose a severe threat to aviation and avian safety. To understand and prevent these bird strikes, knowledge about the factors leading to these bird strikes is vital. However, even though it is a global issue, data availability strongly varies and is difficult to put into a global picture. This paper aims to close this gap by providing an in-depth review of studies and statistics to obtain a concise overview of the bird strike problem in commercial aviation on an international level. The paper illustrates the factors contributing to the occurrence and the potential consequences in terms of effect on flight and damage. This is followed by a presentation of the risk-reducing measures currently in place as well as their limitations. The paper closes with an insight into current research investigating novel methods to prevent bird strikes.

Open heart surgery under acupuncture ? Decrypting a program broadcast on France 2

To analyze a clip from the program ? Acupuncture, osteopathy, hypnosis: do complementary medicines have superpowers ? about acupuncture as an anesthetic for surgical procedures in China. To propose a rational explanation for the phenomena observed. To describe the processes leading a public service broadcasting channel to offer this type of content at prime time and the potential consequences in terms of public health. Analysis using critical thinking attitudes and skills, along with a bibliographical search of Medline, Google Scholar and Cochrane Library databases. The information delivered in the television clip is ambiguous. It does not allow the viewer to form an informed opinion on the relevance of acupuncture as an anesthetic for surgical procedures. It is reasonable to assume that the clip shows surgery performed with undisclosed epidural anesthesia coupled with mild intravenous anesthesia, sometimes performed in other countries. What needs to be highlighted here is the overestimation of acupuncture added to the protocol. The media tend to exaggerate the risks and expected effects of the treatments they report on, which can lead patients to turn to unproven therapies. Broadcasting such a clip at prime time underlines the urgent need for the public and all health professionals to be trained in sorting and critically analyzing health information.

Towards Multilife Marketing: How Goods Multiple Lives Practices Create Value for Consumers

ABSTRACTGoods multiple lives practices (GMLPs) encompass a wide range of diverse practices that extend product lifecycles. We propose that it is through a holistic consideration of the concept that it is possible to understand its breadth and scope as well as its potential consequences in terms of increased value for consumers. Through 15 in-depth interviews and secondary data analysis, this study explores the value-creating potential of GMLPs for consumers. The results suggest that these practices are based upon three key dimensions to create perceived value for consumers: polymorphous exchanges, protean intermediation, and multichannel structuration.

Dopamine-dependent effects on basal and glutamate stimulated network dynamics in cultured hippocampal neurons.

Oscillatory activity occurs in cortical and hippocampal networks with specific frequency ranges thought to be critical to working memory, attention, differentiation of neuronal precursors, and memory trace replay. Synchronized activity within relatively large neuronal populations is influenced by firing and bursting frequency within individual cells, and the latter is modulated by changes in intrinsic membrane excitability and synaptic transmission. Published work suggests that dopamine, a potent modulator of learning and memory, acts on dopamine receptor 1-like dopamine receptors to influence the phosphorylation and trafficking of glutamate receptor subunits, along with long-term potentiation of excitatory synaptic transmission in striatum and prefrontal cortex. Prior studies also suggest that dopamine can influence voltage gated ion channel function and membrane excitability in these regions. Fewer studies have examined dopamine's effect on related endpoints in hippocampus, or potential consequences in terms of network burst dynamics. In this study, we record action potential activity using a microelectrode array system to examine the ability of dopamine to modulate baseline and glutamate-stimulated bursting activity in an invitro network of cultured murine hippocampal neurons. We show that dopamine stimulates a dopamine type-1 receptor-dependent increase in number of overall bursts within minutes of its application. Notably, however, at the concentration used herein, dopamine did not increase the overall synchrony of bursts between electrodes. Although the number of bursts normalizes by 40min, bursting in response to a subsequent glutamate challenge is enhanced by dopamine pretreatment. Dopamine-dependent potentiation of glutamate-stimulated bursting was not observed when the two modulators were administered concurrently. In parallel, pretreatment of murine hippocampal cultures with dopamine stimulated lasting increases in the phosphorylation of the glutamate receptor subunit GluA1 at serine 845. This effect is consistent with the possibility that enhanced membrane insertion of GluAs may contribute to a more slowly evolving dopamine-dependent potentiation of glutamate-stimulated bursting. Together, these results are consistent with the possibility that dopamine can influence hippocampal bursting by at least two temporally distinct mechanisms, contributing to an emerging appreciation of dopamine-dependent effects on network activity in the hippocampus.

Revisiting the Pharmacokinetic Profiles of Gadolinium-Based Contrast Agents

Gadolinium-based contrast agents (GBCAs) have been used for years for magnetic resonance imaging examinations. Because of their rapid blood clearance, they were considered as very safe products until some of them were shown to induce nephrogenic systemic fibrosis in patients with renal failure and hypersignals on T1-weighted unenhanced brain scans of patients with normal renal function. To date, these adverse effects have been related almost exclusively to the use of low-stability linear agents, which are more prone to release free gadolinium. The aim of the present meta-analysis was to ascertain the existence of a deep compartment for gadolinium storage in the body and to assess whether all the GBCAs present the same toxicokinetic profile. Applying a systematic literature search methodology, all clinical and preclinical studies reporting time-dependent plasma concentrations and renal excretion data of gadolinium were identified and analyzed. Since the individual data were not available, the analysis focused on the average values per groups of subjects or animals, which had received a given GBCA at a given dose. The rate constants of the distribution phase (α), rapid elimination phase (β), and residual excretion phase (γ) of gadolinium were determined in each group from the plasma concentration (Cp) time curves and the relative urinary excretion rate (rER) time curves, taking the 2-hour time point as a reference. Moreover, as bone may represent a reservoir for long-term gadolinium accumulation and slow release into the blood stream, the time curves of the relative concentration in the bone (rCB) of Gd-labeled GBCAs in mice or rats were analyzed taking day 1 concentrations as a reference. The ratio of gadolinium concentrations in the bone marrow (CBM) as compared with the bone (CB) was also calculated. The relative urinary excretion rate (rER) plots revealed a prolonged residual excretion phase of gadolinium in healthy volunteers, consistent with the existence of a deep compartment of distribution for the GBCAs. The rate constant γ of gadoterate meglumine (0.107 hour) is 5 times higher than that of the linear agents (0.020 ± 0.008 hour), indicating a much faster blood clearance for the macrocyclic GBCA. Similar results were obtained in the preclinical studies. A strong correlation was shown between the γ values of the different products and their respective thermodynamic stability constants (Ktherm). Greater clearance rates of Gd from murine bone were also found after gadoterate meglumine or gadoteridol injection (0.131-0.184 day) than after administration of the linear agents (0.004-0.067 day). The concentrations of Gd in the bone marrow (CBM) from animals exposed to either gadoterate meglumine or gadodiamide are higher than those in the bone (CB) for at least 24 hours. Moreover, the ratio of concentrations (CBM/CB) at 4 hours is significantly lower with the former agent than the latter (1.9 vs 6.5, respectively). Using a nonconventional pharmacokinetic approach, we showed that gadoterate meglumine undergoes a much faster residual excretion from the body than the linear GBCAs, a process that seems related to the thermodynamic stability of the different chelates. Gadolinium dissociation occurs in vivo for some linear chelates, a mechanism that may explain their long-term retention and slow release from bone. Potential consequences in terms of bone toxicity warrant further investigations.

Behavioural changes in marmots in relation to livestock grazing disturbance: an experimental test

In high-altitude rangeland environments in Nepal and other Himalayan countries, grazing by domestic livestock poses a threat to local wildlife, in terms of competition for resources and other deleterious changes in behaviour. An experimental approach (before-during-after design) was used to investigate the effects of disturbance by livestock and attending herder on the behaviour of the Himalayan marmot (Marmota himalayana)—a common burrowing animal. When disturbed by livestock and herder, marmots reduced their foraging activities and conversely increased vigilance levels. After livestock and herder had departed from a marmot colony, the marmots mostly returned to their normal behaviour; however, prolonged vigilance activity was observed. Marmots appear to have habituated to livestock and herder to some extent, but still responding to the livestock and herder by modifying their behaviour. Increased vigilance behaviour at the expense of foraging time may have potential consequences in terms of meeting energy budgets for winter hibernation. Therefore, future increases in livestock numbers could have a deleterious effect on marmots and other ground-dwelling wildlife in the region.

The dynamical landscape of marine phytoplankton diversity.

Observations suggest that the landscape of marine phytoplankton assemblage might be strongly heterogeneous at the dynamical mesoscale and submesoscale (10-100 km, days to months), with potential consequences in terms of global diversity and carbon export. But these variations are not well documented as synoptic taxonomic data are difficult to acquire. Here, we examine how phytoplankton assemblage and diversity vary between mesoscale eddies and submesoscale fronts. We use a multi-phytoplankton numerical model embedded in a mesoscale flow representative of the North Atlantic. Our model results suggest that the mesoscale flow dynamically distorts the niches predefined by environmental contrasts at the basin scale and that the phytoplankton diversity landscape varies over temporal and spatial scales that are one order of magnitude smaller than those of the basin-scale environmental conditions. We find that any assemblage and any level of diversity can occur in eddies and fronts. However, on a statistical level, the results suggest a tendency for larger diversity and more fast-growing types at fronts, where nutrient supplies are larger and where populations of adjacent water masses are constantly brought into contact; and lower diversity in the core of eddies, where water masses are kept isolated long enough to enable competitive exclusion.

Nostalgic constructions of nurse education in British national newspapers.

To explore nostalgic constructions of nurse education in British National newspapers. British newspaper discourse relating to the increased academic level of nurse education in the UK is negative, evoking comparisons between negative constructions of nurse education in the present and an idealized nostalgic view of the past. Discussion paper. This study used a critical discourse analysis approach to analyse 11 British Newspaper articles, which exemplify nostalgic constructions of nurse education. This was a purposive sample from a database search (LexisNexis) of British national newspaper articles relating to the increasing academic level of nurse education in the period from 1999-2012. A dominant nostalgic discourse constructs a 'golden era' of nurse education, which idealizes the past, making the present flawed in comparison. Nostalgic constructions create group identities creating contrasting 'caring' nurses educated in the idealized past with those educated now, who are perceived as too educated to care. An inherent characteristic of the nostalgic discourse is the notion that the solution to current problems with nurse education is a return to an idealized version of the past. Another less common newspaper discourse views nostalgia as a problematic construct. Nostalgic discourse with a focus on the past potentially acts as a barrier to creating an effective nurse education system for the 21(st) Century. This focus on an idealized past also has potential consequences in terms of public opinion and legitimization of government policy, which might otherwise be viewed as retrograde.

Atrial fibrillation at mid-term after bioprosthetic aortic valve replacement – implications for anti-thrombotic therapy.

Little is known about mid-term (3-month) postoperative atrial fibrillation (MT-POAF) in patients treated with bioprosthetic aortic valve replacement (BAVR). The aim of this study was to describe the natural history, identify the predictors and investigate the potential consequences in terms of anti-thrombotic therapy. During a longitudinal, prospective study, 219 patients were treated with BAVR early (7 days) and at mid-term postoperatively (30 and 90 days). POAF was monitored and risk factors were identified on logistic regression analysis. History of previous AF (OR, 3.08; 95% CI: 1.35-6.98), early POAF (OR, 5.93; 95% CI: 2.96-11.8), and BMI (per 5 kg/m(2): OR, 1.46; 95% CI: 1.03-2.09), were independent predictors for MT-POAF whereas sex, age and Euroscore were not. Results were identical when restricted to the 176 patients free from preoperative AF. In this subgroup, 36 patients (20.4%) had MT-POAF; 33 out of 174 (18.7%) would have required anticoagulation (CHA2DS2VASc score ≥ 1). Conversely, patients with BMI <27.7 and sinus rhythm at early follow-up had a very low risk of MT-POAF (OR, 0.16; 95% CI: 0.06-0.42). There was a higher than expected occurrence of MT-POAF in patients treated with BAVR, particularly in overweight patients with early POAF. This raises the question of implementing an anti-thrombotic therapy in these patients at higher risk of delayed atrial arrhythmia.

Discordance in the minimal inhibitory concentrations of ertapenem for Enterobacter cloacae: Vitek 2 system versus Etest and agar dilution methods

Our objective was to compare the ertapenem minimal inhibitory concentrations (MICs) for Enterobacter cloacae isolates categorized intermediate or resistant to ertapenem when measured with the Vitek 2 system, with the MICs for these isolates when measured by two methods performed in agar medium: the Etest and agar plate dilution method (APDM). Overall, 50 E. cloacae isolates were included in the study. The mean MIC of ertapenem was 2.92±1.77μg/ml according to the Vitek 2 system, 0.94±0.84μg/ml according to the Etest strips, and 0.93±0.62μg/ml according to the APDM. Furthermore, the MICs determined by the Vitek 2 system were higher than the MICs determined by the two other methods for 96% of strains. Lastly, according to the Etest strips and APDM, 42% of E. cloacae were susceptible to ertapenem. No carbapenemase was identified by the screening method used. Using the Vitek 2 system to determine ertapenem MICs for E. cloacae can have potential consequences in terms of additional carbapenemase-detecting tests and antimicrobial therapy. It would be interesting to determine if the Vitek 2 system is more effective for the detection of carbapenemase producers with low-level carbapenem resistance than the two methods performed in agar medium.

Macroautophagy Regulation during HIV-1 Infection of CD4+ T Cells and Macrophages

Autophagy is an intracellular mechanism whereby pathogens, particularly viruses, are destroyed in autolysosomes after their entry into targets cells. Therefore, to survive and replicate in host cells, viruses have developed multiple strategies to either counteract or exploit this process. The aim of this review is to outline the known relationships between HIV-1 and autophagy in CD4+ T lymphocytes and macrophages, two main HIV-1 cell targets. The differential regulation of autophagy in these two cell-types is highlighted and its potential consequences in terms of viral replication and physiopathology discussed.

Abstract P100: The Cardiovascular Consequences of Switching From Atorvastatin to Generic Simvastatin in the Netherlands

OBJECTIVES In January 2009, an authorisation form was implemented which required Dutch clinicians to justify the prescription of branded statins. The effect was significant switching of patients from atorvastatin to generic simvastatin. However, current prescription data indicates that much of this switching is occurring at less than equipotent doses. We sought to assess the potential consequences in terms of cardiovascular disease (CVD). METHODS Data from a pharmacy database covering the majority of drug dispenses in the Netherlands informed dose-specific patterns of switching from atorvastatin to generic simvastatin among 39,031 Dutch patients in Q1 2009. Dose-specific, lipid-modifying potencies of the two statins were derived from a recently-published meta-analysis. The relationship between reduction in LDL-C achieved by statin therapy and relative reduction in risk of CVD was derived from a recently-published meta-regression. This showed that for every 25mg/dL (0.65mmol/L) reduction in LDL-C, the relative risk (RR) (95% confidence interval [CI]) for any CVD event, a coronary event, stroke and cardiovascular death were 0.86 (95%CI 0.84-0.88), 0.84 (95%CI 0.82-0.86), 0.90 (95%CI 0.86-0.94) and 0.89 (95%CI 0.87-0.92), respectively. RESULTS In Q1 2009, 33.7%, 47.2% and 19.1% of Dutch patients initially on atorvastatin were switched to less potent, equipotent and more potent doses of simvastatin, respectively. The net (weighted-average) effect would have been a 5.6% increase in LDL-C. The predicted relative increases (95%CI) in risk of various cardiovascular events are dependent on baseline LDL-C, and are summarized in the Table . CONCLUSIONS In the Netherlands, many patients are being switched from atorvastatin to generic simvastatin at inferior doses, which might lead to a significant increase in future cardiovascular events. Baseline LDL-C Any cardiovascular event Coronary event Stroke Cardiovascular death 2.0 mmol/L 2.4% (2.1-2.7) 2.7% (2.4-3.1) 1.7% (1.0-2.4) 1.9% (1.4-2.2) 2.5 mmol/L 3.0% (2.6-3.4) 3.4% (3.0-3.9) 2.1% (1.3-3.0) 2.4% (1.7-2.8) 3.0 mmol/L 3.6% (3.1-4.1) 4.1% (3.6-4.6) 2.6% (1.5-3.6) 2.8% (2.1-3.3) 3.5 mmol/L 4.2% (3.6-4.8) 4.8% (4.2-5.4) 3.0% (1.8-4.2) 3.3% (2.4-3.9) 4.0 mmol/L 4.8% (5.5-4.1) 5.5% (4.8-6.2) 3.4% (2.1-4.8) 3.8% (2.7-4.5)