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Aim. This paper is a report of a study to examine, from the perspective of patients, the impact of venous leg ulcers on health-related quality of life in current and former intravenous drug users and the general population. Background. Venous ulceration can be caused by intravenous drug use. There has been little examination on how this affects the quality of life of this group of patients and how they compare with other patients who have venous ulcers. Method. A qualitative approach was adopted, using framework analysis. Semi-structured interviews with 19 participants who had a venous leg ulcer were conducted between August 2005 and February 2006. Interview audiotapes were analysed to identify recurring themes relating to the impact of venous leg ulcers on overall quality of life. Findings. A complex interaction between symptoms, social restriction and attribution of illness influenced the impact of venous leg ulcers. Smell and pain were the symptoms that had the most profound impacts. In addition to the physical and psychological consequences, participants' activities and social interactions were restricted. Intravenous drug users experienced more social isolation and difficulties in accessing treatment for their venous ulcers. Conclusion. While leg ulcer services remain focused on the needs of older people, services for young intravenous drug users are unlikely to improve. A more coherent and earlier intervention, when the ulcers are not as difficult to treat, would decrease time and costs to the health service. The challenge is to find new ways of providing effective and accessible care to this growing population. [ABSTRACT FROM AUTHOR]

BACKGROUND: Patients experience a wide range of symptoms from varicose veins and are seeking treatment from health care providers. However, there is little data on the relative effectiveness of the treatments available. Patients are therefore often confronted with a choice regarding treatment that they are ill-equipped to make. This lack of certainty and the resultant potential for variability in treatment decisions can mean that patients have expectations that are unrealistic or unfulfilled. AIMS AND OBJECTIVES: The aim of our study was to explore patients' expectations and reasons for seeking treatment for varicose veins. Additional aims included the exploration of symptoms associated with varicose veins and their impact on quality of life. DESIGN: Qualitative study conducted in a large NHS Trust. METHODS: A total of 16 patients, who had been referred to a specialist vascular service for the treatment of varicose veins, were recruited. Semi-structured interviews were used to explore the patients' reasons for seeking treatment. Framework analysis was used to analyse the data from the anonymized transcripts. RESULTS: Participants attributed a wide range of symptoms to their varicose veins, and were actively seeking treatment with the expectation that they would gain symptom relief. The symptoms attributed to their varicose veins had a significant negative impact on their quality of life and lifestyle. Improving the cosmetic appearance of their legs was seen as a secondary benefit. CONCLUSIONS: The perceived symptoms of varicose veins can impact on lifestyle and quality of life. Patients seek treatment with the expectation of treatment outcomes that are not supported by robust clinical evidence. Appropriate education and management of such expectations are an essential step in caring for this group of patients. RELEVANCE TO CLINICAL PRACTICE: Nurses are caring for patients with varicose veins in a range of clinical settings. When caring and providing information for this group of patients, nurses need to be aware of the impact of varicose vein symptoms and to understanding that patients may have unrealistic expectations or invalid reasons for seeking treatment. [ABSTRACT FROM AUTHOR]

Brain-computer interfaces (BCIs) have the potential to restore hand movement for people with paralysis, but current devices still lack the fine control required to interact with objects of daily living. Following our understanding of cortical activity during arm reaches, hand BCI studies have focused primarily on velocity control. However, mounting evidence suggests that posture, and not velocity, dominates in hand-related areas. To explore whether this signal can causally control a prosthesis, we developed a BCI training paradigm centered on the reproduction of posture transitions. Monkeys trained with this protocol were able to control a multidimensional hand prosthesis with high accuracy, including execution of the very intricate precision grip. Analysis revealed that the posture signal in the target grasping areas was the main contributor to control. We present, for the first time, neural posture control of a multidimensional hand prosthesis, opening the door for future interfaces to leverage this additional information channel., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Family caregivers provide the majority of long-term care and support of older adults as they age or approach the end of life. Studies often refer to family caregivers as invisible because the American healthcare system, public policy, and society do not support or recognize their work. Family caregivers who provide care to older adults who live in rural areas face unique challenges due to the rural environment. The purpose of this study was to inductively develop a theoretical framework that explains the process of family caregiving to older adults who live at home in rural areas and require daily assistance while exploring their experiences regarding access, utilization, challenges, and effectiveness of patient healthcare services and caregiver resources in rural areas. The grounded theory method of Strauss and Corbin was used for sampling, data collection, and data analysis. Fifteen family caregivers who oversaw and/or provided care on a daily basis to an older adult living in two rural counties of New York State participated in the study. Data were collected through two semi-structured interviews with each participant, yielding 30 interviews. Findings revealed that family caregivers engaged in the process of orchestrating care by growing into caregiving, integrating technology, and utilizing networks when providing and managing caregiving. Understanding caregiving from the perspective of family caregivers engaged in the process can inform healthcare practice, healthcare education, and public policy and can support better outcomes for both older adults and their family caregivers., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Artificial neural networks (ANNs) are a powerful class of computational models for unravelling neural mechanisms of brain function. However, for neural control of movement, they currently must be integrated with software simulating biomechanical effectors, leading to limiting impracticalities: (1) researchers must rely on two different platforms and (2) biomechanical effectors are not generally differentiable, constraining researchers to reinforcement learning algorithms despite the existence and potential biological relevance of faster training methods. To address these limitations, we developed MotorNet, an open-source Python toolbox for creating arbitrarily complex, differentiable, and biomechanically realistic effectors that can be trained on user-defined motor tasks using ANNs. MotorNet is designed to meet several goals: ease of installation, ease of use, a high-level user-friendly application programming interface, and a modular architecture to allow for flexibility in model building. MotorNet requires no dependencies outside Python, making it easy to get started with. For instance, it allows training ANNs on typically used motor control models such as a two joint, six muscle, planar arm within minutes on a typical desktop computer. MotorNet is built on PyTorch and therefore can implement any network architecture that is possible using the PyTorch framework. Consequently, it will immediately benefit from advances in artificial intelligence through PyTorch updates. Finally, it is open source, enabling users to create and share their own improvements, such as new effector and network architectures or custom task designs. MotorNet's focus on higher-order model and task design will alleviate overhead cost to initiate computational projects for new researchers by providing a standalone, ready-to-go framework, and speed up efforts of established computational teams by enabling a focus on concepts and ideas over implementation., Competing Interests: OC, JM, MK, PG No competing interests declared, JP Reviewing editor, eLife, (© 2023, Codol et al.)

Neurons coordinate their activity to produce an astonishing variety of motor behaviors. Our present understanding of motor control has grown rapidly thanks to new methods for recording and analyzing populations of many individual neurons over time. In contrast, current methods for recording the nervous system's actual motor output - the activation of muscle fibers by motor neurons - typically cannot detect the individual electrical events produced by muscle fibers during natural behaviors and scale poorly across species and muscle groups. Here we present a novel class of electrode devices ('Myomatrix arrays') that record muscle activity at unprecedented resolution across muscles and behaviors. High-density, flexible electrode arrays allow for stable recordings from the muscle fibers activated by a single motor neuron, called a 'motor unit,' during natural behaviors in many species, including mice, rats, primates, songbirds, frogs, and insects. This technology therefore allows the nervous system's motor output to be monitored in unprecedented detail during complex behaviors across species and muscle morphologies. We anticipate that this technology will allow rapid advances in understanding the neural control of behavior and identifying pathologies of the motor system., Competing Interests: BC, MZ, KT, JM, AJ, AP, MW, KN, LT, EA, LO, NO, RG, PA, JL, YW, MK, TO, RK, AM, SO, RW, HM, AM, CL, GK, JK, WO, KQ, PP, GG, AT, SC, TK, TS, BB, MZ, CT, SG, AP, MG, EA, NT, DO, BT, SL, MC, RC, JP, SS No competing interests declared, CP, MB Reviewing editor, eLife, (© 2023, Chung, Zia et al.)

Circular extrachromosomal DNA (ecDNA) in patient tumors is an important driver of oncogenic gene expression, evolution of drug resistance and poor patient outcomes. Applying computational methods for the detection and reconstruction of ecDNA across a retrospective cohort of 481 medulloblastoma tumors from 465 patients, we identify circular ecDNA in 82 patients (18%). Patients with ecDNA-positive medulloblastoma were more than twice as likely to relapse and three times as likely to die within 5 years of diagnosis. A subset of tumors harbored multiple ecDNA lineages, each containing distinct amplified oncogenes. Multimodal sequencing, imaging and CRISPR inhibition experiments in medulloblastoma models reveal intratumoral heterogeneity of ecDNA copy number per cell and frequent putative 'enhancer rewiring' events on ecDNA. This study reveals the frequency and diversity of ecDNA in medulloblastoma, stratified into molecular subgroups, and suggests copy number heterogeneity and enhancer rewiring as oncogenic features of ecDNA., (© 2023. The Author(s).)

In recent years many countries have created national bodies that provide evidence-based guidance and policy relating to the commissioning and provision of healthcare services. However, such guidance often fails to be consistently implemented. The differing perspectives from which guidance is developed is suggested as a significant contributor to these failures. A societal perspective is, necessarily, taken by policy makers, while patients and their healthcare professionals are primarily concerned with an individual perspective. This is particularly likely to impair implementation where national policy objectives, such as cost effectiveness, equity, or the promotion of innovation, are embodied in the guidance, while patients and healthcare professionals may consider it appropriate to over-ride these, based upon individual circumstances and preferences. This paper examines these conflicts with reference to guidance issued by the National Institute of Health and Care Excellence in England. Conflicts are identified between the objectives, values, and preferences of those who develop and those who implement such guidance, with consequent difficulties in providing helpful personalised recommendations. The implications of this for the development and implementation of guidance are discussed and recommendations are made regarding the ways in which such guidance is framed and disseminated., Competing Interests: Declaration of Competing Interest Both authors declare funding from the NIHR Programme Development Grants Programme (NIHR202042). JM has previously chaired a National Institute of Health and Care Excellence (NICE) Guideline Development Group and been vice chair of the NICE Appraisals Committee., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Varicose vein (VV) treatments have changed significantly in recent years leading to potential disparities in service provision. The aim of this study was to examine the trends in VV treatment in England and to identify disparities in the provision of day-case and inpatient treatments related to deprivation, ethnicity, and other demographic, and geographical factors., Method: A population-based study using linked hospital episode statistics for England categorized VV procedures and compared population rates and procedure characteristics by ethnicity, deprivation quintile, and geographical area., Results: A total of 311 936 people had 389 592 VV procedures between 2006/07 and 2017/18, with a further 63 276 procedures between 2018/19 and 2020/21. Procedure rates have reduced in all but the oldest age groups, whereas endovenous procedures have risen to more than 60 per cent of the total in recent years. In younger age groups there was a 20-30 per cent reduction in procedure rates for the least-deprived compared with the most-deprived quintiles. Non-white ethnicity was associated with lower procedure rates. Large regional and local differences were identified in standardized rates of VV procedures. In the most recent 5-year interval, the North-East region had a three-fold higher rate than the South-East region with evidence of greater variation between commissioners in overall rates, the proportion of endovenous procedures, and policies regarding bilateral treatments., Conclusions: There are substantial geographical variations in the provision of treatment for VVs, which are not explained by demographic differences. These have persisted, despite the publication of guidelines from the National Institute for Health and Care Excellence, and many commissioners, and providers would seem to implement policies that are contrary to this guidance. Lower rates of procedures in less-deprived areas may reflect treatments carried out in private practice, which are not included in these data., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd.)

Many healthcare agencies are producing evidence-based guidance and policy that may determine the availability of particular healthcare products and procedures, effectively rationing aspects of healthcare. They claim legitimacy for their decisions through reference to evidence-based scientific method and the implementation of just decision-making procedures, often citing the criteria of 'accountability for reasonableness'; publicity, relevance, challenge and revision, and regulation. Central to most decision methods are estimates of gains in quality-adjusted life-years (QALY), a measure that combines the length and quality of survival. However, all agree that the QALY alone is not a sufficient measure of all relevant aspects of potential healthcare benefits, and a number of value assessment frameworks have been suggested. I argue that the practical implementation of these procedures has the potential to lead to a distorted assessment of value. Undue weight may be ascribed to certain attributes, particularly those that favour commercial or political interests, while other attributes that are highly valued by society, particularly those related to care processes, may be omitted or undervalued. This may be compounded by a lack of transparency to relevant stakeholders, resulting in an inability for them to participate in, or challenge, the decisions. The makes it likely that costly new technologies, for which inflated prices can be justified by the current value frameworks, are displacing aspects of healthcare that are highly valued by society., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

One of the primary ways we interact with the world is using our hands. In macaques, the circuit spanning the anterior intraparietal area, the hand area of the ventral premotor cortex, and the primary motor cortex is necessary for transforming visual information into grasping movements. However, no comprehensive model exists that links all steps of processing from vision to action. We hypothesized that a recurrent neural network mimicking the modular structure of the anatomical circuit and trained to use visual features of objects to generate the required muscle dynamics used by primates to grasp objects would give insight into the computations of the grasping circuit. Internal activity of modular networks trained with these constraints strongly resembled neural activity recorded from the grasping circuit during grasping and paralleled the similarities between brain regions. Network activity during the different phases of the task could be explained by linear dynamics for maintaining a distributed movement plan across the network in the absence of visual stimulus and then generating the required muscle kinematics based on these initial conditions in a module-specific way. These modular models also outperformed alternative models at explaining neural data, despite the absence of neural data during training, suggesting that the inputs, outputs, and architectural constraints imposed were sufficient for recapitulating processing in the grasping circuit. Finally, targeted lesioning of modules produced deficits similar to those observed in lesion studies of the grasping circuit, providing a potential model for how brain regions may coordinate during the visually guided grasping of objects., Competing Interests: The authors declare no competing interest.

The rapid development in healthcare technologies in recent years has resulted in the need for health services, whether publicly funded or insurance based, to identify means to maximise the benefits and provide equitable distribution of limited resources. This has resulted in the need for rationing decisions, and there has been considerable debate regarding the substantive and procedural ethical principles that promote distributive justice when making such decisions. In this paper, I argue that while the scientifically rigorous approaches of evidence-based healthcare are claimed as aspects of procedural justice that legitimise such guidance, there are biases and distortions in all aspects of the process that may lead to epistemic injustices. Regardless of adherence to principles of distributive justice in the decision-making process, evidential failings may undermine the fairness and legitimacy of such decisions. In particular, I identify epistemic exclusion that denies certain patient and professional groups the opportunity to contribute to the epistemic endeavour. This occurs at all stages of the process, from the generation, analysis and reporting of the underlying evidence, through the interpretation of such evidence, to the decision-making that determines access to healthcare resources. I further argue that this is compounded by processes which confer unwarranted epistemic privilege on experts in relation to explicit or implicit value judgements, which are not within their remit. I suggest a number of areas in which changes to the processes for developing, regulating, reporting and evaluating evidence may improve the legitimacy of such processes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Monolithic capacitors operating at radio frequencies (RF) serve as critical components in integrated circuits for wireless communication. Design and fabrication innovations for high capacitance density RF capacitors are highly desired for the miniaturization of RFIC chips. However, practical and simple solutions are limited by existing capabilities in three-dimensional (3D) structure construction and the effective configuration of electrodes. We report a unique route to achieve unprecedentedly high capacitance density at a high operating frequency through a capacitor configuration of 3D coil interdigital electrodes using planar semiconductor processing compatible materials and fabrication methods. A systematic mechanical-electrical design principle is demonstrated, and fabricated devices show a maximum 21.5 pF capacitance, which is 17.2× larger after rolling up. The corresponding capacitance density is as large as 371 pF mm -2 , with resonant frequency of 1.5 GHz. The performance could be improved significantly by simply rolling up more turns with minimal change to the area footprint.

Aim: To identify the symptoms and quality of life impacts that are important from the perspective of patients with varicose veins and to compare identified themes to items in varicose vein patient-reported outcome measures (PROMs)., Background: Varicose veins are common worldwide and are considered a chronic condition with implications for quality of life. Treatment is predominantly conservative; therefore, understanding patients' experiences of living with varicose veins is important to inform the provision of clinical care. PROMs are often used to collect data about patients' quality of life., Design: Thematic synthesis of qualitative research reported according to ENTREQ guidelines., Methods: Multiple electronic databases, including MEDLINE and CINAHL, were systematically searched to identify qualitative research examining experiences of adults with varicose veins. Thematic synthesis was then conducted on the included studies., Results: Three studies met the inclusion criteria; the quality of the studies was high. The range and intensity of reported symptoms and participant's experiences of living with varicose veins were varied. Five overarching themes were identified: physical, psychological and social impact of varicose veins, adapting to varicose veins and reasons for seeking treatment. The overall key theme to emerge was adaptation, with patients demonstrating how they adapted to the various impacts., Conclusion: This review demonstrates that varicose veins have a wide range of symptoms and may have a significant impact on quality of life; people made significant adaptations to enable them to live their lives as fully as possible., Relevance to Clinical Practice: Healthcare professionals need to be aware of the range of symptoms and their impact on quality of life. The use of PROMs to gather information about quality of life and symptoms is well established globally; however, PROMs currently used may not capture the full extent of the impact on patient's quality of life., (© 2018 John Wiley & Sons Ltd.)

Considerable progress has been made over the last decades in characterizing the neural coding of hand shape, but grasp force has been largely ignored. We trained two macaque monkeys (Macaca mulatta) on a delayed grasping task where grip type and grip force were instructed. Neural population activity was recorded from areas relevant for grasp planning and execution: the anterior intraparietal area (AIP), F5 of the ventral premotor cortex, and the hand area of the primary motor cortex (M1). Grasp force was strongly encoded by neural populations of all three areas, thereby demonstrating for the first time the coding of grasp force in single- and multi-units of AIP. Neural coding of intended grasp force was most strongly represented in area F5. In addition to tuning analysis, a dimensionality reduction method revealed low-dimensional responses to grip type and grip force. Additionally, this method revealed a high correlation between latent variables of the neural population representing grasp force and the corresponding latent variables of electromyographic forearm muscle activity. Our results therefore suggest an important role of the cortical areas AIP, F5, and M1 in coding grasp force during movement execution as well as of F5 for coding intended grasp force.

Background: E-cigarettes, nicotine transdermal patches, and nicotine chewing gum are occasionally used as cigarette replacements by patients, but it is unknown if their use is a safe alternative to smoking in the perioperative period., Methods: All patients undergoing major surgery at a single outpatient ambulatory surgery center for a 5-year period were tested for urine cotinine, a nicotine metabolite, the day of surgery. Patients were divided into 4 groups: never smoked (group A), quit smoking with negative urine test (group B), continued to smoke (group C), and quit smoking with positive urine test (group D). Statistical significance of complications among groups was tested using right tailed chi-square test and point biserial correlation coefficient calculations. To control for confounding factors, age and BMI of each group were compared using unequal sample size and variance t tests., Results: Four hundred seventy patients were included in the study. Patient count in each group was group A n = 380, group B n = 48, group C n = 32, and group D n = 10. Complication frequency was as follows D > C > A > B. Statistically significant differences were observed between D + C (cotinine positive) and A + B (cotinine negative) P = 0.0001 and between D (nicotine replacement) and B (nicotine abstinence) P = 0.00026. There was neither statistical difference between groups A and B, nor C and D., Conclusions: Nicotine replacement carries similar risks as continued smoking and is not as safe as abstinence in the perioperative period in plastic surgery patients. Importantly, patients who stopped smoking for the surgery had equivalent risk for postoperative complications as patients who had never smoked.

Directing neurons to form predetermined circuits with the intention of treating neurological disorders and neurodegenerative diseases is a fundamental goal and current challenge in neuroengineering. Until recently, only neuronal aggregates were studied and characterized in culture, which can limit information gathered to populations of cells. In this study, we use a substrate constructed of arrays of strain-induced self-rolled-up membrane 3D architectures. This results in changes in the neuronal architecture and altered growth dynamics of neurites. Hippocampal neurons from postnatal rats were cultured at low confluency (∼250 cells mm -2 ) on an array of transparent rolled-up microtubes (μ-tubes; 4-5 μm diameter) of varying topographical arrangements. Neurite growth on the μ-tubes was characterized and compared to controls in order to establish a baseline for alignment imposed by the topography. Compared to control substrates, neurites are significantly more aligned toward the 0° reference on the μ-tube array. Pitch (20-60 and 100 μm) and μ-tube length (30-80 μm) of array elements were also varied to investigate their impact on neurite alignment. We found that alignment was improved by the gradient pitch arrangement and with longer μ-tubes. Application of this technology will enhance the ability to construct intentional neural circuits through array design and manipulation of individual neurons and can be adapted to address challenges in neural repair, reinnervation, and neuroregeneration.

Despite exercise being included in the recommended advice for patients with venous leg ulcers, there is a fear shared by clinicians and patients that exercise may be either inappropriate or harmful and actually delay rather than promote healing. Therefore, before implementing a larger-scale study exploring the effects of a supervised exercise programme in patients with venous ulcers being treated with compression therapy, it is important to assess exercise safety as well as fidelity and progression in a feasibility study. Eighteen participants randomised in the exercise group were asked to undertake 36 (3 times/week for 12 weeks) 60-min exercise sessions, each comprising moderate-intensity aerobic, resistance, and flexibility exercise components. For the purposes of this paper, we analysed the data collected during the exercise sessions. The overall session attendance rate was 79%, with 13 of 18 participants completing all sessions. No in-session adverse events were reported; 100% aerobic components and 91% of resistance components were completed within the desired moderate-intensity target. Similarly, 81% of aerobic components and 93% of flexibility components were completed within the prescribed duration targets. Our data showed that patients with venous ulcers could safely follow a supervised exercise programme incorporating moderate-intensity aerobic, resistance, and flexibility components., (© 2018 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: A third of deaths in the UK from ruptured abdominal aortic aneurysm (AAA) are in women. In men, national screening programmes reduce deaths from AAA and are cost-effective. The benefits, harms, and cost-effectiveness in offering a similar programme to women have not been formally assessed, and this was the aim of this study., Methods: We developed a decision model to assess predefined outcomes of death caused by AAA, life years, quality-adjusted life years, costs, and the incremental cost-effectiveness ratio for a population of women invited to AAA screening versus a population who were not invited to screening. A discrete event simulation model was set up for AAA screening, surveillance, and intervention. Relevant women-specific parameters were obtained from sources including systematic literature reviews, national registry or administrative databases, major AAA surgery trials, and UK National Health Service reference costs., Findings: AAA screening for women, as currently offered to UK men (at age 65 years, with an AAA diagnosis at an aortic diameter of ≥3·0 cm, and elective repair considered at ≥5·5cm) gave, over 30 years, an estimated incremental cost-effectiveness ratio of £30 000 (95% CI 12 000-87 000) per quality-adjusted life year gained, with 3900 invitations to screening required to prevent one AAA-related death and an overdiagnosis rate of 33%. A modified option for women (screening at age 70 years, diagnosis at 2·5 cm and repair at 5·0 cm) was estimated to have an incremental cost-effectiveness ratio of £23 000 (9500-71 000) per quality-adjusted life year and 1800 invitations to screening required to prevent one AAA-death, but an overdiagnosis rate of 55%. There was considerable uncertainty in the cost-effectiveness ratio, largely driven by uncertainty about AAA prevalence, the distribution of aortic sizes for women at different ages, and the effect of screening on quality of life., Interpretation: By UK standards, an AAA screening programme for women, designed to be similar to that used to screen men, is unlikely to be cost-effective. Further research on the aortic diameter distribution in women and potential quality of life decrements associated with screening are needed to assess the full benefits and harms of modified options., Funding: UK National Institute for Health Research Health Technology Assessment programme., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licence. Published by Elsevier Ltd.. All rights reserved.)

Background: Abdominal aortic aneurysm (AAA) screening programmes have been established for men in the UK to reduce deaths from AAA rupture. Whether or not screening should be extended to women is uncertain., Objective: To evaluate the cost-effectiveness of population screening for AAAs in women and compare a range of screening options., Design: A discrete event simulation (DES) model was developed to provide a clinically realistic model of screening, surveillance, and elective and emergency AAA repair operations. Input parameters specifically for women were employed. The model was run for 10 million women, with parameter uncertainty addressed by probabilistic and deterministic sensitivity analyses., Setting: Population screening in the UK., Participants: Women aged ≥ 65 years, followed up to the age of 95 years., Interventions: Invitation to ultrasound screening, followed by surveillance for small AAAs and elective surgical repair for large AAAs., Main Outcome Measures: Number of operations undertaken, AAA-related mortality, quality-adjusted life-years (QALYs), NHS costs and cost-effectiveness with annual discounting., Data Sources: AAA surveillance data, National Vascular Registry, Hospital Episode Statistics, trials of elective and emergency AAA surgery, and the NHS Abdominal Aortic Aneurysm Screening Programme (NAAASP)., Review Methods: Systematic reviews of AAA prevalence and, for elective operations, suitability for endovascular aneurysm repair, non-intervention rates, operative mortality and literature reviews for other parameters., Results: The prevalence of AAAs (aortic diameter of ≥ 3.0 cm) was estimated as 0.43% in women aged 65 years and 1.15% at age 75 years. The corresponding attendance rates following invitation to screening were estimated as 73% and 62%, respectively. The base-case model adopted the same age at screening (65 years), definition of an AAA (diameter of ≥ 3.0 cm), surveillance intervals (1 year for AAAs with diameter of 3.0-4.4 cm, 3 months for AAAs with diameter of 4.5-5.4 cm) and AAA diameter for consideration of surgery (5.5 cm) as in NAAASP for men. Per woman invited to screening, the estimated gain in QALYs was 0.00110, and the incremental cost was £33.99. This gave an incremental cost-effectiveness ratio (ICER) of £31,000 per QALY gained. The corresponding incremental net monetary benefit at a threshold of £20,000 per QALY gained was -£12.03 (95% uncertainty interval -£27.88 to £22.12). Almost no sensitivity analyses brought the ICER below £20,000 per QALY gained; an exception was doubling the AAA prevalence to 0.86%, which resulted in an ICER of £13,000. Alternative screening options (increasing the screening age to 70 years, lowering the threshold for considering surgery to diameters of 5.0 cm or 4.5 cm, lowering the diameter defining an AAA in women to 2.5 cm and lengthening the surveillance intervals for the smallest AAAs) did not bring the ICER below £20,000 per QALY gained when considered either singly or in combination., Limitations: The model for women was not directly validated against empirical data. Some parameters were poorly estimated, potentially lacking relevance or unavailable for women., Conclusion: The accepted criteria for a population-based AAA screening programme in women are not currently met., Future Work: A large-scale study is needed of the exact aortic size distribution for women screened at relevant ages. The DES model can be adapted to evaluate screening options in men., Study Registration: This study is registered as PROSPERO CRD42015020444 and CRD42016043227., Funding: The National Institute for Health Research Health Technology Assessment programme., Competing Interests: Jonathan A Michaels reports grants outside the submitted work from the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme (grant number RP-PG-1210-12009). Janet T Powell report grants from NIHR (HTA 07/37/64) outside the submitted work.

Our voluntary grasping actions lie on a continuum between immediate action and waiting for the right moment, depending on the context. Therefore, studying grasping requires an investigation into how preparation time affects this process. Two macaque monkeys ( Macaca mulatta ; one male, one female) performed a grasping task with a short instruction followed by an immediate or delayed go cue (0-1300 ms) while we recorded in parallel from neurons in the grasp preparation relevant area F5 that is part of the ventral premotor cortex, and the anterior intraparietal area (AIP). Initial population dynamics followed a fixed trajectory in the neural state space unique to each grip type, reflecting unavoidable movement selection, then diverged depending on the delay, reaching unique states not achieved for immediately cued movements. Population activity in the AIP was less dynamic, whereas F5 activity continued to evolve throughout the delay. Interestingly, neuronal populations from both areas allowed for a readout tracking subjective anticipation of the go cue that predicted single-trial reaction time. However, the prediction of reaction time was better from F5 activity. Intriguingly, activity during movement initiation clustered into two trajectory groups, corresponding to movements that were either "as fast as possible" or withheld movements, demonstrating a widespread state shift in the frontoparietal grasping network when movements must be withheld. Our results reveal how dissociation between immediate and delay-specific preparatory activity, as well as differentiation between cortical areas, is possible through population-level analysis. SIGNIFICANCE STATEMENT Sometimes when we move, we consciously plan our movements. At other times, we move instantly, seemingly with no planning at all. Yet, it's unclear how preparation for movements along this spectrum of planned and seemingly unplanned movement differs in the brain. Two macaque monkeys made reach-to-grasp movements after varying amounts of preparation time while we recorded from the premotor and parietal cortex. We found that the initial response to a grasp instruction was specific to the required movement, but not to the preparation time, reflecting required movement selection. However, when more preparation time was given, neural activity achieved unique states that likely related to withholding movements and anticipation of movement, shedding light on the roles of the premotor and parietal cortex in grasp planning., (Copyright © 2018 the authors 0270-6474/18/385759-15$15.00/0.)

Background: Venous leg ulcers (VLUs) are typically painful and heal slowly. Compression therapy offers high healing rates; however, improvements are not usually sustained. Exercise is a low-cost, low-risk and effective strategy for improving physical and mental health. Little is known about the feasibility and efficacy of supervised exercise training used in combination with compression therapy patients with VLUs., Objectives: To assess the feasibility of a 12-week supervised exercise programme as an adjunct therapy to compression in patients with VLUs., Methods: This was a two-centre, two-arm, parallel-group, randomized feasibility trial. Thirty-nine patients with venous ulcers were recruited and randomized 1 : 1 either to exercise (three sessions weekly) plus compression therapy or compression only. Progress/success criteria included exercise attendance rate, loss to follow-up and patient preference. Baseline assessments were repeated at 12 weeks, 6 months and 1 year, with healing rate and time, ulcer recurrence and infection incidents documented. Intervention and healthcare utilization costs were calculated. Qualitative data were collected to assess participants' experiences., Results: Seventy-two per cent of the exercise group participants attended all scheduled exercise sessions. No serious adverse events and only two exercise-related adverse events (both increased ulcer discharge) were reported. Loss to follow-up was 5%. At 12 months, median ulcer healing time was lower in the exercise group (13 vs. 34·7 weeks). Mean National Health Service costs were £813·27 for the exercise and £2298·57 for the control group., Conclusions: The feasibility and acceptability of both the supervised exercise programme in conjunction with compression therapy and the study procedures is supported., (© 2017 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Purpose: To investigate the effects of a 12-week supervised exercise programme on lower-limb cutaneous microvascular reactivity in adults with venous leg ulceration., Methods: Thirty-eight adults with unilateral venous ulceration who were being treated with lower-limb compression therapy (58% male; mean age 65 years; median ulcer size 5 cm 2 ) were randomly allocated to exercise or control groups. Exercise participants (n = 18) were invited to attend thrice weekly sessions of lower-limb aerobic and resistance exercise for 12 weeks. Cutaneous microvascular reactivity was assessed in the gaiter region of ulcerated and non-ulcerated legs at baseline and 3 months using laser Doppler fluxmetry coupled with iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). Cutaneous vascular conductance (CVC) was calculated as laser Doppler flux (AU)/mean arterial pressure (mmHg)., Results: Thirty-seven participants completed follow-up assessments. Median session attendance was 36 (range 2-36). Analyses of covariance revealed greater peak CVC responses to ACh in the exercise group at 3 months in both the ulcerated (adjusted difference = 0.944 AU/mmHg; 95% CI 0.504-1.384) and non-ulcerated (adjusted difference = 0.596 AU/mmHg; 95% CI 0.028-1.164) legs. Peak CVC responses to SNP were also greater in the exercise group at 3 months in the ulcerated leg (adjusted difference = 0.882 AU/mmHg; 95% CI 0.274-1.491), but not the non-ulcerated leg (adjusted difference = 0.392 AU/mmHg; 95% CI - 0.377 to 1.161)., Conclusion: Supervised exercise training improves lower-limb cutaneous microvascular reactivity in adults with venous leg ulceration.

Preparing and executing grasping movements demands the coordination of sensory information across multiple scales. The position of an object, required hand shape, and which of our hands to extend must all be coordinated in parallel. The network formed by the macaque anterior intraparietal area (AIP) and hand area (F5) of the ventral premotor cortex is essential in the generation of grasping movements. Yet, the role of this circuit in hand selection is unclear. We recorded from 1342 single- and multi-units in AIP and F5 of two macaque monkeys (Macaca mulatta) during a delayed grasping task in which monkeys were instructed by a visual cue to perform power or precision grips on a handle presented in five different orientations with either the left or right hand, as instructed by an auditory tone. In AIP, intended hand use (left vs. right) was only weakly represented during preparation, while hand use was robustly present in F5 during preparation. Interestingly, visual-centric handle orientation information dominated AIP, while F5 contained an additional body-centric frame during preparation and movement. Together, our results implicate F5 as a site of visuo-motor transformation and advocate a strong transition between hand-independent and hand-dependent representations in this parieto-frontal circuit.

Background: Hospitals that conduct more procedures on the carotid arteries may achieve better outcomes. In the context of ongoing reconfiguration of UK vascular services, this systematic review was conducted to evaluate the relationship between the volume of carotid procedures and outcomes, including mortality and stroke., Methods: Searches of electronic databases identified studies that reported the effect of hospital or clinician volume on outcomes. Reference and citation searches were also performed. Inclusion was restricted to European populations on the basis that the model of healthcare delivery is similar across Europe, but differs from that in the USA and elsewhere. Analyses of hospital and clinician volume, and carotid endarterectomy (CEA) and carotid artery stenting (CAS) were conducted separately., Results: Eleven eligible studies were identified (233 411 participants), five from the UK, two from Sweden, one each from Germany, Finland and Italy, and a combined German, Austrian and Swiss population. All studies were observational. Two large studies (179 736 patients) suggested an inverse relationship between hospital volume and mortality (number needed to treat (NNT) as low as 165), and combined mortality and stroke (NNT as low as 93), following CEA. The evidence was less clear for CAS; multiple analyses in three studies did not identify convincing evidence of an association. Limited data are available on the relationship between clinician volume and outcome in CAS; in CEA, an inverse relationship was identified by two of three small studies., Conclusion: The evidence from the largest and highest-quality studies included in this review support the centralization of CEA., (© 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Recent models of movement generation in motor cortex have sought to explain neural activity not as a function of movement parameters, known as representational models, but as a dynamical system acting at the level of the population. Despite evidence supporting this framework, the evaluation of representational models and their integration with dynamical systems is incomplete in the literature. Using a representational velocity-tuning based simulation of center-out reaching, we show that incorporating variable latency offsets between neural activity and kinematics is sufficient to generate rotational dynamics at the level of neural populations, a phenomenon observed in motor cortex. However, we developed a covariance-matched permutation test (CMPT) that reassigns neural data between task conditions independently for each neuron while maintaining overall neuron-to-neuron relationships, revealing that rotations based on the representational model did not uniquely depend on the underlying condition structure. In contrast, rotations based on either a dynamical model or motor cortex data depend on this relationship, providing evidence that the dynamical model more readily explains motor cortex activity. Importantly, implementing a recurrent neural network we demonstrate that both representational tuning properties and rotational dynamics emerge, providing evidence that a dynamical system can reproduce previous findings of representational tuning. Finally, using motor cortex data in combination with the CMPT, we show that results based on small numbers of neurons or conditions should be interpreted cautiously, potentially informing future experimental design. Together, our findings reinforce the view that representational models lack the explanatory power to describe complex aspects of single neuron and population level activity., Competing Interests: The authors have declared that no competing interests exist.

The functional communication of neurons in cortical networks underlies higher cognitive processes. Yet, little is known about the organization of the single neuron network or its relationship to the synchronization processes that are essential for its formation. Here, we show that the functional single neuron network of three fronto-parietal areas during active behavior of macaque monkeys is highly complex. The network was closely connected (small-world) and consisted of functional modules spanning these areas. Surprisingly, the importance of different neurons to the network was highly heterogeneous with a small number of neurons contributing strongly to the network function (hubs), which were in turn strongly inter-connected (rich-club). Examination of the network synchronization revealed that the identified rich-club consisted of neurons that were synchronized in the beta or low frequency range, whereas other neurons were mostly non-oscillatory synchronized. Therefore, oscillatory synchrony may be a central communication mechanism for highly organized functional spiking networks., Competing Interests: The authors declare that no competing interests exist.

Background: Intermittent claudication (IC) is a symptom of peripheral arterial disease (PAD) and is associated with high morbidity and mortality. Pentoxifylline, one of many drugs used to treat IC, acts by decreasing blood viscosity, improving erythrocyte flexibility and promoting microcirculatory flow and tissue oxygen concentration. Many studies have evaluated the efficacy of pentoxifylline in treating individuals with PAD, but results of these studies are variable. This is an update of a review first published in 2012., Objectives: To determine the efficacy of pentoxifylline in improving the walking capacity (i.e. pain-free walking distance and total (absolute, maximum) walking distance) of individuals with stable intermittent claudication, Fontaine stage II., Search Methods: For this update, the Cochrane Vascular Group Trials Search Co-ordinator searched the Specialised Register (last searched April 2015) and the Cochrane Register of Studies (2015, Issue 3)., Selection Criteria: All double-blind, randomised controlled trials (RCTs) comparing pentoxifylline versus placebo or any other pharmacological intervention in patients with IC Fontaine stage II., Data Collection and Analysis: Two review authors separately assessed included studies,. matched data and resolved disagreements by discussion. Review authors assessed the methodological quality of studies by using the Cochrane 'Risk of bias' tool and collected results related to pain-free walking distance (PFWD) and total walking distance (TWD). Comparison of studies was based on duration and dose of pentoxifylline., Main Results: We included in this review 24 studies with 3377 participants. Seventeen studies compared pentoxifylline versus placebo. In the seven remaining studies, pentoxifylline was compared with flunarizine (one study), aspirin (one study), Gingko biloba extract (one study), nylidrin hydrochloride (one study), prostaglandin E1 (two studies) and buflomedil and nifedipine (one study). The quality of the evidence was generally low, with large variability in reported findings.. Most included studies did not report on random sequence generation and allocation concealment, did not provide adequate information to allow selective reporting to be judged and did not report blinding of assessors. Heterogeneity between included studies was considerable with regards to multiple variables, including duration of treatment, dose of pentoxifylline, baseline walking distance and participant characteristics; therefore, pooled analysis was not possible.Of 17 studies comparing pentoxifylline with placebo, 14 reported TWD and 11 reported PFWD; the difference in percentage improvement in TWD for pentoxifylline over placebo ranged from 1.2% to 155.9%, and in PFWD from -33.8% to 73.9%. Testing the statistical significance of these results generally was not possible because data were insufficient. Most included studies suggested improvement in PFWD and TWD for pentoxifylline over placebo and other treatments, but the statistical and clinical significance of findings from individual trials is unclear. Pentoxifylline generally was well tolerated; the most commonly reported side effects consisted of gastrointestinal symptoms such as nausea., Authors' Conclusions: Given the generally poor quality of published studies and the large degree of heterogeneity evident in interventions and in results, the overall benefit of pentoxifylline for patients with Fontaine class II intermittent claudication remains uncertain. Pentoxifylline was shown to be generally well tolerated.Based on total available evidence, high-quality data are currently insufficient to reveal the benefits of pentoxifylline for intermittent claudication.

Neural networks of the brain involved in the planning and execution of grasping movements are not fully understood. The network formed by macaque anterior intraparietal area (AIP) and hand area (F5) of the ventral premotor cortex is implicated strongly in the generation of grasping movements. However, the differential role of each area in this frontoparietal network is unclear. We recorded spiking activity from many electrodes in parallel in AIP and F5 while three macaque monkeys (Macaca mulatta) performed a delayed grasping task. By analyzing neural population activity during action preparation, we found that state space analysis of simultaneously recorded units is significantly more predictive of subsequent reaction times (RTs) than traditional methods. Furthermore, because we observed a wide variety of individual unit characteristics, we developed the sign-corrected average rate (SCAR) method of neural population averaging. The SCAR method was able to explain at least as much variance in RT overall as state space methods. Overall, F5 activity predicted RT (18% variance explained) significantly better than AIP (6%). The SCAR methods provides a straightforward interpretation of population activity, although other state space methods could provide richer descriptions of population dynamics. Together, these results lend support to the differential role of the parietal and frontal cortices in preparation for grasping, suggesting that variability in preparatory activity in F5 has a more potent effect on trial-to-trial RT variability than AIP., Significance Statement: Grasping movements are planned before they are executed, but how is the preparatory activity in a population of neurons related to the subsequent reaction time (RT)? A population analysis of the activity of many neurons recorded in parallel in macaque premotor (F5) and parietal (AIP) cortices during a delayed grasping task revealed that preparatory activity in F5 could explain a threefold larger fraction of variability in trial-to-trial RT than AIP. These striking differences lend additional support to a differential role of the parietal and premotor cortices in grasp movement preparation, suggesting that F5 has a more direct influence on trial-to-trial variability and movement timing, whereas AIP might be more closely linked to overall movement intentions., (Copyright © 2015 the authors 0270-6474/15/3511415-18$15.00/0.)

Background: There have been rapid technological developments aimed at improving short- and long-term results of percutaneous transluminal balloon angioplasty (PTA) in peripheral arterial occlusive disease (PAD)., Objectives: To assess current clinical effectiveness and cost-effectiveness evidence of additional techniques to standard PTA for PAD, develop a health economic model to assess cost-effectiveness and to identify where further research is needed., Data Sources: Relevant electronic databases, including MEDLINE, EMBASE and The Cochrane Library were searched from inception to 2011, between May and October 2011., Methods: Systematic reviews were conducted of clinical effectiveness and cost-effectiveness. The population was participants with symptomatic PAD undergoing endovascular treatment for disease distal to the inguinal ligament. Interventions were modifications of and adjuncts to PTA in the peripheral circulation, compared with conventional PTA. Outcomes included measures of clinical effectiveness and costs. Data were extracted from randomised controlled trials (RCTs), which were quality assessed using standard criteria. Where appropriate, meta-analyses using fixed- and random-effects methods produced relative risks (RRs). A discrete-event simulation model was developed to assess the relative cost-effectiveness of the interventions from a NHS perspective over a lifetime. The patient populations of intermittent claudication (IC) and critical limb ischaemia (CLI) were modelled separately. Univariate and probabilistic sensitivity analyses were undertaken., Results: In total, 40 RCTs were included, many of which had small sample sizes. Significantly reduced restenosis rates were shown in meta-analyses of self-expanding stents (SES) {RR 0.67 [95% confidence interval (CI) 0.52 to 0.87]}, endovascular brachytherapy (EVBT) [RR 0.63 (95% CI 0.48 to 0.83)] at 12 months and drug-coated balloons (DCBs) at 6 months [RR 0.40 (95% CI 0.23 to 0.69)], and single studies of stent-graft or drug-eluting stent (DES), compared with PTA; a single study showed improvements with DES versus bare-metal stents (BMSs). Compared with PTA, walking capacity was not significantly affected by cutting balloon, balloon-expandable stents or EVBT; in SES, there was evidence of improvement in walking capacity after up to 12 months. The use of DCBs dominated both the assumed standard practice of PTA with bailout BMS and all other interventions because it lowered lifetime costs and improved quality of life (QoL). These results were seen for both patient populations (IC and CLI). Sensitivity analyses showed that the results were robust to different assumptions about the clinical benefits attributable to the interventions, suggesting that the use of DCBs is cost-saving., Limitations: Differing definitions of restenosis made direct comparison across trials difficult. There were few data available for walking capacity and QoL., Conclusions: The evidence showed a significant benefit to reducing restenosis rates for self-expanding and DESs, stent-graft, EVBT and DCBs. If it is assumed that patency translates into beneficial long-term clinical outcomes, then DCB and bail-out DES are most likely to be the cost-effective enhancements to PTA. A RCT comparing current recommended practice (PTA with bail-out BMS) with DCB and bail-out DES could assess long-term follow-up and cost-effectiveness. Data relating patency status to the need for reintervention and to the probability of symptoms returning should be collected, as should health-related QoL measures [European Quality of Life-5 Dimensions (EQ-5D) and maximum walking distance]., Study Registration: This study is registered as PROSPERO CRD42012002014., Funding: The National Institute for Health Research Health Technology Assessment programme.

Background: An abnormal dilatation of the abdominal aorta is referred to as an abdominal aortic aneurysm (AAA). Due to the risk of rupture, surgical repair is offered electively to individuals with aneurysms greater than 5.5 cm in size. Traditionally, conventional open surgical repair (OSR) was considered the first choice approach. However, over the past two decades endovascular aneurysm repair (EVAR) has gained popularity as a treatment option. This article intends to review the role of EVAR in the management of elective AAA., Objectives: To assess the effectiveness of EVAR versus conventional OSR in individuals with AAA considered fit for surgery, and EVAR versus best medical care in those considered unfit for surgery. This was determined by the effect on short, intermediate and long-term mortality, endograft related complications, re-intervention rates and major complications., Search Methods: The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (January 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 12). The TSC also searched trial databases for details of ongoing or unpublished studies., Selection Criteria: Prospective randomised controlled trials (RCTs) comparing EVAR with OSR in individuals with AAA considered fit for surgery. and comparing EVAR with best medical care in individuals considered unfit for surgery. We excluded studies with inadequate data or using an inadequate randomisation technique., Data Collection and Analysis: Three reviewers independently evaluated trials for appropriateness for inclusion and extracted data using pro forma designed by the Cochrane PVD Group. We assessed the quality of trials using The Cochrane Collaboration's 'Risk of bias' tool. We entered collected data in to Review Manager (version 5.2.3) for analysis. Where direct comparisons could be made, we determined odds ratios (OR). We tested studies for heterogeneity and, when present, we used a random-effects model; otherwise we used a fixed-effect model. We tabulated data that could not be collated., Main Results: Four high-quality trials comparing EVAR with OSR (n = 2790) and one high-quality trial comparing EVAR with no intervention (n = 404) fulfilled the inclusion criteria. In individuals considered fit for surgery, a pooled analysis, including 1362 individuals randomised to EVAR and 1361 randomised to OSR, found short-term mortality (including 30-day or inhospital mortality, excluding deaths prior to intervention) with EVAR to be significantly lower than with OSR (1.4% versus 4.2%, OR 0.33, 95% confidence interval (CI) 0.20 to 0.55; P < 0.0001). Using intention-to-treat analysis (ITT) there was no significant difference in mortality at intermediate follow-up (up to four years from randomisation), with 221 (15.8%) and 237 (17%) deaths in the EVAR (n = 1393) and OSR (n = 1390) groups, respectively (OR 0.92, 95% CI 0.75 to 1.12; P = 0.40). There was also no significant difference in long-term mortality (beyond four years), with 464 (37.3%) deaths in the EVAR and 470 (37.8%) deaths in the OSR group (OR 0.98, 95% CI 0.83 to 1.15; P = 0.78). Similarly, there was no significant difference in aneurysm-related mortality between groups, either at the intermediate- or long-term follow up.Studies showed that both EVAR and OSR were associated with similar incidences of cardiac deaths (OR 1.14, 95% CI 0.86 to 1.52; P = 0.36) and fatal stroke rate (OR 0.81, 95% CI 0.42 to 1.55; P = 0.52). The long-term reintervention rate was significantly higher in the EVAR group than in the OSR group (OR 1.98, 95% CI 1.12 to 3.51; P = 0.02; I(2) = 85%). Results of the reintervention analysis should be interpreted with caution due to significant heterogeneity. Operative complications, health-related quality of life and sexual dysfunction were generally comparable between the EVAR and OSR groups. However, there was a slightly higher incidence of pulmonary complications in the OSR group compared with the EVAR group (OR 0.36, 95% CI 0.17 to 0.75; P = 0.006).In individuals considered unfit for conventional OSR, the one included trial found no difference between the EVAR and no-intervention groups with regard to all-cause mortality at final follow up, with 21.0 deaths per 100 person-years in the EVAR group and 22.1 deaths per 100 person years in the no-intervention group (adjusted hazard ratio (HR) with EVAR 0.99, 95% CI 0.78 to 1.27; P = 0.97). Aneurysm-related deaths were, however, significantly higher in the no-intervention group than in the EVAR group (adjusted HR 0.53, 95% CI 0.32 to 0.89; P = 0.02). There was no difference in myocardial events (HR 1.07, 95% CI 0.60 to 1.91) between the groups in this study., Authors' Conclusions: In individuals considered fit for conventional surgery, EVAR was associated with lower short-term mortality than OSR. However, this benefit from EVAR did not persist at the intermediate- and long-term follow ups. Individuals undergoing EVAR had a higher reintervention rate than those undergoing OSR. Most of the reinterventions undertaken following EVAR, however, were catheter-based interventions associated with low mortality. Operative complications, health-related quality of life and sexual dysfunction were generally comparable between EVAR and OSR. However, there was a slightly higher incidence of pulmonary complications in the OSR group than in the EVAR group.In individuals considered unfit for open surgery, the results of a single trial found no overall short- or long-term benefits of EVAR over no intervention with regard to all-cause mortality, but individuals may differ and individual preferences should always be taken into account.

Background: The aim was to perform an economic evaluation of the cost-effectiveness of endovascular enhancements to percutaneous transluminal balloon angioplasty (PTA) with bail-out bare metal stents for infrainguinal peripheral arterial disease., Methods: The following interventions were considered: PTA with no bail-out stenting, PTA with bail-out drug-eluting stents, drug-coated balloons, primary bare metal stents, primary drug-eluting stents, endovascular brachytherapy, stent-grafts and cryoplasty. A discrete-event simulation model was developed to assess the relative cost-effectiveness of the interventions from a health service perspective over a lifetime. Populations of patients with intermittent claudication (IC) and critical leg ischaemia (CLI) were modelled separately. Univariable and probabilistic sensitivity analyses were undertaken. Effectiveness was measured by quality-adjusted life-years (QALYs)., Results: For both patient populations, the use of drug-coated balloons dominated all other options by having both lower lifetime costs and greater effectiveness. For willingness-to-pay thresholds between £0 and £100,000 per additional QALY, the probability of drug-coated balloons being cost-effective was at least 58.3 per cent for patients with IC and at least 72.2 per cent for patients with CLI. Sensitivity analyses showed that the results were robust to different assumptions regarding the clinical benefits attributable to the interventions., Conclusion: The use of drug-coated balloons represents a cost-effective alternative to the use of PTA with bail-out bare metal stents., (© 2013 Crown copyright. British Journal of Surgery © 2013 British Journal of Surgery Society Ltd.)

Background: There are several additional techniques designed to enhance conventional percutaneous transluminal balloon angioplasty (PTA). This systematic review assessed current evidence on the clinical effectiveness of additional techniques for infrainguinal peripheral arterial occlusive disease (PAD)., Methods: Relevant electronic databases, including MEDLINE, were searched in May 2011. The population comprised participants with symptomatic PAD undergoing endovascular treatment for disease distal to the inguinal ligament. Interventions were additional techniques compared with conventional PTA. Main outcome measures were restenosis and need for reintervention. Randomized clinical trials (RCTs) of clinical effectiveness were assessed for quality and data were extracted. Where appropriate, meta-analysis was undertaken to produce risk ratios (RRs)., Results: Forty RCTs were selected. Meta-analysis showed a significant benefit in reducing restenosis rates at 6 months for self-expanding stents (RR 0.49) and drug-coated balloons (RR 0.40), and at 12 months for endovascular brachytherapy (RR 0.63). There was also evidence that use of a stent-graft significantly reduced restenosis compared with PTA, as did drug-eluting stents compared with bare-metal stents. Meta-analysis showed that use of drug-coated balloons was associated with significantly lower reintervention rates than PTA alone at 6 months (RR 0.24) and 24 months (RR 0.27) of follow-up. There was also evidence of significantly lower reintervention rates for self-expanding stents at 6 months. Other techniques did not show significant treatment effects for restenosis or reintervention., Conclusion: The conclusions of this review should be tempered by small sample sizes, lack of clinical outcome measures and differing outcome definitions, making direct comparison across trials difficult. However, self-expanding stents, drug-eluting stents and drug-coated balloons appeared to be the most promising technologies worthy of future study., (© 2013 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Background: Varicose vein surgery is a common surgical procedure but there is no consensus regarding the best surgical technique. The use of tourniquets during varicose vein surgery has been advocated as a means of reducing the potential for blood loss during the operation., Objectives: To identify whether the use of a tourniquet should be recommended when undertaking surgery for the management of primary varicose veins., Search Methods: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched April 2013) and the CENTRAL (2013, Issue 3)., Selection Criteria: All studies described as randomised controlled trials that examined the use of tourniquets during surgery for patients with primary varicose veins were included., Data Collection and Analysis: Data from eligible studies were extracted and summarised independently by two authors. All studies were cross-checked independently by the authors., Main Results: No additional studies were included or excluded in the updated review. Twenty papers detailing 18 trials were considered. Only three trials were randomised controlled trials and were included in the review. The remaining fifteen studies were excluded for various reasons. All three included trials had a small sample size and reported the trial design, outcome measures and analysis poorly. There were also variations in the outcome measures used between the trials. In addition, there was no consistency on the reporting of mean and medians for blood loss during the operation. It was therefore not possible to pool the data to perform meta-analysis. However, the reported blood loss when using a tourniquet was between 0 and 16 ml compared to between 107 to 133 ml when not using a tourniquet (P < 0.01)., Authors' Conclusions: Although there were significant quality issues with the available evidence, the use of a tourniquet would appear to reduce blood loss during surgery. There were no reported differences between the use or non-use of a tourniquet in terms of complications and morbidity. However, the available trials were not of sufficient size to detect rarer complications such as nerve damage.