Complex Polyploids: Origins, Genomic Composition, and Role of Introgressed Alleles.

Introgression allows polyploid species to acquire new genomic content from diploid progenitors or from other unrelated diploid or polyploid lineages, contributing to genetic diversity and facilitating adaptive allele discovery. In some cases, high levels of introgression elicit the replacement of large numbers of alleles inherited from the polyploid's ancestral species, profoundly reshaping the polyploid's genomic composition. In such complex polyploids it is often difficult to determine which taxa were the progenitor species and which taxa provided additional introgressive blocks through subsequent hybridization. Here, we use population-level genomic data to reconstruct the phylogenetic history of Betula pubescens (downy birch), a tetraploid species often assumed to be of allopolyploid origin and which is known to hybridize with at least four other birch species. This was achieved by modeling of polyploidization and introgression events under the multispecies coalescent and then using an approximate Bayesian computation (ABC) rejection algorithm to evaluate and compare competing polyploidization models. We provide evidence that B. pubescens is the outcome of an autoploid genome doubling event in the common ancestor of B. pendula and its extant sister species, B. platyphylla, that took place approximately 178,000-188,000 generations ago. Extensive hybridization with B. pendula, B. nana, and B. humilis followed in the aftermath of autopolyploidization, with the relative contribution of each of these species to the B. pubescens genome varying markedly across the species' range. Functional analysis of B. pubescens loci containing alleles introgressed from B. nana identified multiple genes involved in climate adaptation, while loci containing alleles derived from B. humilis revealed several genes involved in the regulation of meiotic stability and pollen viability in plant species.

Phylogenetic Analysis of Allotetraploid Species Using Polarized Genomic Sequences.

Phylogenetic analysis of polyploid hybrid species has long posed a formidable challenge as it requires the ability to distinguish between alleles of different ancestral origins in order to disentangle their individual evolutionary history. This problem has been previously addressed by conceiving phylogenies as reticulate networks, using a two-step phasing strategy that first identifies and segregates homoeologous loci and then, during a second phasing step, assigns each gene copy to one of the subgenomes of an allopolyploid species. Here, we propose an alternative approach, one that preserves the core idea behind phasing-to produce separate nucleotide sequences that capture the reticulate evolutionary history of a polyploid-while vastly simplifying its implementation by reducing a complex multistage procedure to a single phasing step. While most current methods used for phylogenetic reconstruction of polyploid species require sequencing reads to be pre-phased using experimental or computational methods-usually an expensive, complex, and/or time-consuming endeavor-phasing executed using our algorithm is performed directly on the multiple-sequence alignment (MSA), a key change that allows for the simultaneous segregation and sorting of gene copies. We introduce the concept of genomic polarization that, when applied to an allopolyploid species, produces nucleotide sequences that capture the fraction of a polyploid genome that deviates from that of a reference sequence, usually one of the other species present in the MSA. We show that if the reference sequence is one of the parental species, the polarized polyploid sequence has a close resemblance (high pairwise sequence identity) to the second parental species. This knowledge is harnessed to build a new heuristic algorithm where, by replacing the allopolyploid genomic sequence in the MSA by its polarized version, it is possible to identify the phylogenetic position of the polyploid's ancestral parents in an iterative process. The proposed methodology can be used with long-read and short-read high-throughput sequencing data and requires only one representative individual for each species to be included in the phylogenetic analysis. In its current form, it can be used in the analysis of phylogenies containing tetraploid and diploid species. We test the newly developed method extensively using simulated data in order to evaluate its accuracy. We show empirically that the use of polarized genomic sequences allows for the correct identification of both parental species of an allotetraploid with up to 97% certainty in phylogenies with moderate levels of incomplete lineage sorting (ILS) and 87% in phylogenies containing high levels of ILS. We then apply the polarization protocol to reconstruct the reticulate histories of Arabidopsis kamchatica and Arabidopsis suecica, two allopolyploids whose ancestry has been well documented. [Allopolyploidy; Arabidopsis; genomic polarization; homoeologs; incomplete lineage sorting; phasing; polyploid phylogenetics; reticulate evolution.].

Radiometric analysis of haze in bright-annealed AISI 430 ferritic stainless steel.

The influence of both topography and optical constants on the optical reflection of bright-annealed AISI 430 ferritic stainless steel has been analyzed to correlate these characteristics with the occurrence of the unwanted haze effect in industrial products. This work reports the analysis of the total-integrated-scattering spectra of bright-annealed AISI 430 ferritic steel plates, on the basis of the microfacet model for the bidirectional reflectance function developed by He and Torrance [Siggraph '91, Proc. of the 18th Annual Conference on Computer Graphics and Interactive Techniques, (1991), p. 175]. Such an approach allows for modeling the optical reflection of these stainless-steel industrial products based on roughness parameters, root-mean square height, and autocorrelation length, derived from scale-limited topographic maps. The functional choice of the cutoff wavelength in the high-pass Gaussian filtering of the topographic map is proven critical. Additionally, optical constants n and k of the steels are estimated based on their total reflection spectra, measured in an 8°/di optical geometry. The results suggest that the haze effect could be due to a non-controlled increase in the thickness of the passive layer during the bright-annealing process.

Physiotherapy rehabilitation for osteoporotic vertebral fracture-a randomised controlled trial and economic evaluation (PROVE trial).

The trial compared three physiotherapy approaches: manual or exercise therapy compared with a single session of physiotherapy education (SSPT) for people with osteoporotic vertebral fracture(s). At 1 year, there were no statistically significant differences between the groups meaning there is inadequate evidence to support manual or exercise therapy. INTRODUCTION: To evaluate the clinical and cost-effectiveness of different physiotherapy approaches for people with osteoporotic vertebral fracture(s) (OVF). METHODS: >Prospective, multicentre, adaptive, three-arm randomised controlled trial. Six hundred fifteen adults with back pain, osteoporosis, and at least 1 OVF participated. INTERVENTIONS: 7 individual physiotherapy sessions over 12 weeks focused on either manual therapy or home exercise compared with a single session of physiotherapy education (SSPT). The co-primary outcomes were quality of life and back muscle endurance measured by the QUALEFFO-41 and timed loaded standing (TLS) test at 12 months. RESULTS: At 12 months, there were no statistically significant differences between groups. Mean QUALEFFO-41: - 1.3 (exercise), - 0.15 (manual), and - 1.2 (SSPT), a mean difference of - 0.2 (95% CI, - 3.2 to 1.6) for exercise and 1.3 (95% CI, - 1.8 to 2.9) for manual therapy. Mean TLS: 9.8 s (exercise), 13.6 s (manual), and 4.2 s (SSPT), a mean increase of 5.8 s (95% CI, - 4.8 to 20.5) for exercise and 9.7 s (95% CI, 0.1 to 24.9) for manual therapy. Exercise provided more quality-adjusted life years than SSPT but was more expensive. At 4 months, significant changes above SSPT occurred in endurance and balance in manual therapy, and in endurance for those ≤ 70 years, in balance, mobility, and walking in exercise. CONCLUSIONS: Adherence was problematic. Benefits at 4 months did not persist and at 12 months, we found no significant differences between treatments. There is inadequate evidence a short physiotherapy intervention of either manual therapy or home exercise provides long-term benefits, but arguably short-term benefits are valuable. TRIAL REGISTRATION: ISRCTN 49117867.

Impact of a national enhanced recovery after surgery programme on patient outcomes of primary total knee replacement: an interrupted time series analysis from "The National Joint Registry of England, Wales, Northern Ireland and the Isle of Man".

OBJECTIVE: We aimed to test whether a national Enhanced Recovery After Surgery (ERAS) Programme in total knee replacement (TKR) had an impact on patient outcomes. DESIGN: Natural-experiment (April 2008-December 2016). Interrupted time-series regression assessed impact on trends before-during-after ERAS implementation. SETTING: Primary operations from the UK National Joint Registry (NJR) were linked with Hospital Episode Statistics (HES) data which contains inpatient episodes undertaken in National Health Service (NHS) trusts in England, and Patient Reported Outcome Measures (PROMs). PARTICIPANTS: Patients undergoing primary planned TKR aged ≥18 years. INTERVENTION: ERAS implementation (April 2009-March 2011). OUTCOMES: Regression coefficients of monthly means of Length of stay (LOS), bed day costs, change in Oxford knee scores (OKS) 6-months after surgery, complications (at 6 months), and rates of revision surgeries (at 5 years). RESULTS: 486,579 primary TKRs were identified. Overall LOS and bed-day costs decreased from 5.8 days to 3.7 and from £7607 to £5276, from April 2008 to December 2016. Oxford knee score (OKS) change improved from 15.1 points in April 2008 to 17.1 points in December 2016. Complications decreased from 4.1 % in April 2008 to 1.7 % in March 2016. 5-year revision rates remained stable at 4.8 per 1000 implants years in April 2008 and December 2011. After ERAS, declining trends in LOS and bed costs slowed down; OKS improved, complications remained stable, and revisions slightly increased. CONCLUSIONS: Different secular trends in outcomes for patients having TKR have been observed over the last decade. Although patient outcomes are better than a decade ago ERAS did not improve them at national level.

Healthcare and wider societal implications of stillbirth: a population-based cost-of-illness study.

OBJECTIVE: To extend previous work and estimate health and social care costs, litigation costs, funeral-related costs, and productivity losses associated with stillbirth in the UK. DESIGN: A population-based cost-of-illness study using a synthesis of secondary data. SETTING: The National Health Service (NHS) and wider society in the UK. POPULATION: Stillbirths occurring within a 12-month period and subsequent events occurring over the following 2 years. METHODS: Costs were estimated using published data on events, resource use, and unit costs. MAIN OUTCOME MEASURES: Mean health and social care costs, litigation costs, funeral-related costs, and productivity costs for 2 years, reported for a single stillbirth and at a national level. RESULTS: Mean health and social care costs per stillbirth were £4191. Additionally, funeral-related costs were £559, and workplace absence (parents and healthcare professionals) was estimated to cost £3829 per stillbirth. For the UK, the annual health and social care costs were estimated at £13.6 million, and total productivity losses amounted to £706.1 million (98% of this cost was attributable to the loss of the life of the baby). The figures for total productivity losses were sensitive to the perspective adopted about the loss of life of the baby. CONCLUSION: This work expands the current intelligence on the costs of stillbirth beyond the health service to costs for parents and society, and yet these additional findings must still be regarded as conservative estimates of the true economic costs. TWEETABLE ABSTRACT: The costs of stillbirth are significant, affecting the health service, parents, professionals, and society. PLAIN LANGUAGE SUMMARY: Why and how was the study carried out? The personal, social, and emotional consequences of stillbirth are profound. Placing a monetary value on such consequences is emotive, yet necessary, when deciding how best to invest limited healthcare resources. We estimated the average costs associated with a single stillbirth and the costs for all stillbirths occurring in the UK over a 1-year period. What were the main findings? The average cost to the National Health Service (NHS) of care related to the stillbirth and a first subsequent pregnancy was £4191 for each stillbirth. For the UK, this cost was £13.6 million annually. Clinical negligence payments to bereaved parents were estimated at £2.5 million per year. Parents were estimated to spend £1.8 million per year on funerals. The cost of workplace absence as parents cope with the effects of grief was estimated at £2476 per stillbirth. For the UK, this cost was £8.1 million annually. The loss of a baby is also the loss of an individual with the potential to become a valued and productive member of society. The expected value of an adult's lifetime working hours was taken as an estimate of this productivity loss, and was £213,304 for each stillbirth. The annual cost for all stillbirths was £694 million. We know from parents that the birth of a subsequent child in no way replaces a stillborn baby. We found that 52% of women fall pregnant within 12 months of a stillbirth. From a purely economic perspective concerned only with the number of individuals in society, babies born during this period could potentially replace the productivity losses of the stillborn baby. Adopting this approach, which we understand is controversial and difficult for bereaved parents, the expected productivity losses would be lower, at £333 million. What are the limitations of the work? For some categories, existing data were unavailable and we used clinical opinion to estimate costs. Furthermore, we were unable to quantify some indirect consequences, for example the psychological distress experienced by wider family members. What is the implication for parents? Placing a monetary value on what is for parents a profound personal tragedy may seem unkind. It is, however, unavoidable if we are to provide policy makers with vital information on the wide-ranging consequences that could be prevented through future investments in initiatives to reduce stillbirth.

Xenopus as a model organism to study heterotrimeric G-protein pathway during collective cell migration of neural crest.

Collective cell migration is essential in many fundamental aspects of normal development, like morphogenesis, organ formation, wound healing, and immune responses, as well as in the etiology of severe pathologies, like cancer metastasis. In spite of the huge amount of data accumulated on cell migration, such a complex process involves many molecular actors, some of which still remain to be functionally characterized. One of these signals is the heterotrimeric G-protein pathway that has been studied mainly in gastrulation movements. Recently we have reported that Ric-8A, a GEF for Gα proteins, plays an important role in neural crest migration in Xenopus development. Xenopus neural crest cells, a highly migratory embryonic cell population induced at the border of the neural plate that migrates extensively in order to differentiate in other tissues during development, have become a good model to understand the dynamics that regulate cell migration. In this review, we aim to provide sufficient evidence supporting how useful Xenopus model with its different tools, such as explants and transplants, paired with improved in vivo imaging techniques, will allow us to tackle the multiple signaling mechanisms involved in neural crest cell migration.

Costs of fragility hip fractures globally: a systematic review and meta-regression analysis.

Purpose This study was conducted in order to systematically review the costs of hip fractures globally and identify drivers of differences in costs. Methods A systematic review was conducted to identify studies reporting patient level fragility hip fracture costs between 1990 and 2015. We extracted data on the participants and costs from these studies. Cost data concerning the index hospitalisation were pooled, and a meta-regression was used to examine its potential drivers. We also pooled data on the first-year costs following hip fracture and considered healthcare, social care as well as other cost categories if reported by studies. Results One hundred and thirteen studies reported costs of hip fracture based on patient level data. Patients developing complications as well as patients enrolled in intervention arms of comparative studies were found to have significantly higher costs compared to the controls. The pooled estimate of the cost for the index hospitalisation was $10,075. Health and social care costs at 12 months were $43,669 with inpatient costs being their major driver. Meta-regression analysis identified age, gender and geographic region as being significantly associated with the differences in costs for the index hospitalisation. Conclusion Hip fracture poses a significant economic burden and variation exists in their costs across different regions. We found that there was a considerable variation across studies in terms of study design, methodology, follow-up period, costs considered and results reported that highlights the need for more standardisation in this area of research.

Perceptions of risks for diabetes-related complications in Type 2 diabetes populations: a systematic review.

AIM: In Type 2 diabetes, there is no clear understanding of how people perceive their risk of experiencing diabetes-related complications. To address this issue, we undertook an evidence-based synthesis of how people with Type 2 diabetes perceive their risk of complications. METHODS: We performed a systematic search of nine electronic databases for peer-reviewed articles published on or before 1 March 2016. Data from 18 studies reporting lay perceptions of risks for complications in Type 2 diabetes populations were included. Publication year ranged between 2002 and 2014. RESULTS: Methods used to assess risk perceptions were heterogeneous, ranging from questionnaires measuring the accuracy of perceived risks to semi-structured and focus group interviews. We found evidence of low risk awareness in most dimensions of risk perceptions measured and the existence of optimistic bias. CONCLUSIONS: Perceptions were generally biased and varied according to the dimension of risk measured, the subpopulation concerned and the type of complications considered. Future work is needed to identify the best practical ways of correcting for biased risk perceptions so as to encourage self-care behaviours and treatment adherence.

Investigation of electronic transport under mechanical strain in a molecular junction composed of a polyyne bridge connected to SWCNT electrodes.

In the present work we propose a novel treatment to investigate ballistic electron transport under mechanical strain in a 1-D molecular bridge composed of alternating simple and triple bonds (polyyne) connected between two Single-Wall Carbon Nanotube (SWCNT) electrodes. Calculations with the DFT-NEGF methodology were performed in order to analyze this system at low values of mechanical strain (compression and distension) and at equilibrium length in the presence of bias voltages applied along the longitudinal direction. The results show that, while the mechanical strain displaces the energy levels and changes the band gap in the nanotube caps, the applied bias breaks the degeneracy in the nanotube cap states and defines the electrical conductance along the system. The analysis of the PDOS suggests that the main contribution to the electrical current comes from the superposition of the nanotube cap states, which is in agreement with the transmission calculation, and this device can be employed as a transistor observed in the I-V curve.

The impact of social isolation on delayed hospital discharges of older hip fracture patients and associated costs.

UNLABELLED: Delayed discharges represent an inefficient use of acute hospital beds. Social isolation and referral to a public-funded rehabilitation unit were significant predictors of delayed discharges while admission from an institution was a protective factor for older hip fracture patients. Preventing delays could save between 11.2 and 30.7 % of total hospital costs for this patient group. INTRODUCTION: Delayed discharges of older patients from acute care hospitals are a major challenge for administrative, humanitarian, and economic reasons. At the same time, older people are particularly vulnerable to social isolation which has a detrimental effect on their health and well-being with cost implications for health and social care services. The purpose of the present study was to determine the impact and costs of social isolation on delayed hospital discharge. METHODS: A prospective study of 278 consecutive patients aged 75 or older with hip fracture admitted, as an emergency, to the Orthopaedics Department of Hospital Universitário de Santa Maria, Portugal, was conducted. A logistic regression model was used to examine the impact of relevant covariates on delayed discharges, and a negative binomial regression model was used to examine the main drivers of days of delayed discharges. Costs of delayed discharges were estimated using unit costs from national databases. RESULTS: Mean age at admission was 85.5 years and mean length of stay was 13.1 days per patient. Sixty-two (22.3 %) patients had delayed discharges, resulting in 419 bed days lost (11.5 % of the total length of stay). Being isolated or at a high risk of social isolation, measured with the Lubben social network scale, was significantly associated with delayed discharges (odds ratio (OR) 3.5) as was being referred to a public-funded rehabilitation unit (OR 7.6). These two variables also increased the number of days of delayed discharges (2.6 and 4.9 extra days, respectively, holding all else constant). Patients who were admitted from an institution were less likely to have delayed discharges (OR 0.2) with 5.5 fewer days of delay. Total costs of delayed discharges were between 11.2 and 30.7 % of total costs (€2352 and €9317 per patient with delayed discharge) conditional on whether waiting costs for placement in public-funded rehabilitation unit were included. CONCLUSION: High risk of social isolation, social isolation and referral to public-funded rehabilitation units increase delays in patients' discharges from acute care hospitals.

Impact of hip fracture on hospital care costs: a population-based study.

UNLABELLED: Using a large cohort of hip fracture patients, we estimated hospital costs to be £14,163 and £2139 in the first and second year following fracture, respectively. Second hip and non-hip fractures were major cost drivers. There is a strong economic incentive to identify cost-effective approaches for hip fracture prevention. INTRODUCTION: The purpose of this study was to estimate hospital costs of hip fracture up to 2 years post-fracture and compare costs before and after the index fracture. METHODS: A cohort of patients aged over 60 years admitted with a hip fracture in a UK region between 2003 and 2013 were identified from hospital records and followed until death or administrative censoring. All hospital records were valued using 2012/2013 unit costs, and non-parametric censoring methods were used to adjust for censoring when estimating average annual costs. A generalised linear model examined the main predictors of hospital costs. RESULTS: A cohort of 33,152 patients with a hip fracture was identified (mean age 83 years (SD 8.2). The mean censor-adjusted 1- and 2-year hospital costs after index hip fracture were £14,163 (95 % confidence interval (CI) £14,008 to £14,317) and £16,302 (95 % CI £16,097 to £16,515), respectively. Index admission accounted for 61 % (£8613; 95 % CI £8565 to £8661) of total 1-year hospital costs which were £10,964 higher compared to the year pre-event (p < 0.001). The main predictors of 1-year hospital costs were second hip fracture, other non-hip fragility fractures requiring hospitalisation and hip fracture-related complications. Total UK annual hospital costs associated with incident hip fractures were estimated at £1.1 billion. CONCLUSIONS: Hospital costs following hip fracture are high and mostly occur in the first year after the index hip fracture. Experiencing a second hip fracture after the index fracture accounted for much of the increase in costs. There is a strong economic incentive to prioritise research funds towards identifying the best approaches to prevent both index and subsequent hip fractures.

Comparing the epidemiology of hospital-acquired methicillin-resistant Staphylococcus aureus clone groups in Alberta, Canada.

Patients with methicillin-resistant Staphylococcus aureus (MRSA) clones, which were traditionally seen in the community setting (USA400/CMRSA7 and USA300/CMRSA10), are often identified as hospital-acquired (HA) infections using Infection Prevention and Control (IPC) surveillance definitions. This study examined the demographics and healthcare risk factors of patients with HA-MRSA to help understand if community MRSA clones are from a source internal or external to the hospital setting. Despite USA300/CMRSA10 being the predominant clone in Alberta, hospital clones (USA100/CMRSA2) still dominated in the acute care setting. In the Alberta hospitalized population, patients with USA400/CMRSA7 and USA300/CMRSA10 clones were significantly younger, had fewer comorbidities, and a greater proportion had none or ambulatory care-only healthcare exposure. These findings suggest that there are two distinct populations of HA-MRSA patients, and the patients with USA400/CMRSA7 and USA300/CMRSA10 clones identified in hospital more greatly resemble patients affected by those clones in the community. It is possible that epidemiological assessment overidentifies HA acquisition of MRSA in patients unscreened for MRSA on admission to acute care.

Alcohol abusive use increases facial trauma?

BACKGROUND: Trauma is among the main death causes and morbidity in the world and is often related to the use of alcohol and its abuse has reached massive proportions, no matter if the country is developed or not, being considered as public health problem. Since there are very few randomized and prospective studies in literature about the association of facial trauma and the use of alcohol, this study aims to investigate the impact of alcohol use in facial trauma. MATERIAL AND METHODS: This was a prospective and cross sectional study, involving facial trauma patients attended at Oral Maxillofacial Surgery Division of a State Hospital. Variables included patient's profile, trauma etiology, facial region involved, type of injury and treatment and days of hospitalization. AUDIT test was applied to identify risks and damages of alcohol use and chemical dependence. Absolute distribution, uni and mutilvaried percentages were made for data evaluation. Pearson's qui-squared and Fisher's Exact tests were also used. RESULTS: One hundred patients were evaluated. The patient's mean age was 33.50 years-old, 48% had between 17 and 29 years old, 28% had 30 to 39, and 24% 40 or more. Most of them were male (86%). The most frequent etiology was traffic accident (57%), the extraoral area was most committed (62%), the most frequent type of injury was fractures (78%) and the most affected bone was the mandible (36%). More than half of the patients (53%) had surgical treatment. 38% had their discharge from hospital right after the first attendance. The AUDIT most frequent answer was "moderate use" (46%) and use at risk (39%). There was significant difference between the use of alcohol (AUDIT) and hematoma (0.003) and number of days of hospitalization (p=0.005). CONCLUSIONS: In this study it was not observed association between alcohol consumption using the AUDIT and trauma etiology, but patient victims of traffic accidents were classified as with risk in the scale. Most of the trauma were caused by traffic accidents using motorcycles and occurred in young aged men.

Topographic characterisation of dental implants for commercial use.

BACKGROUND: To characterize the surface topography of several dental implants for commercial use. MATERIAL AND METHODS: Dental implants analyzed were Certain (Biomet 3i), Tissue Level (Straumann), Interna (BTI), MG-InHex (MozoGrau), SPI (Alphabio) and Hikelt (Bioner). Surface topography was ascertained using a confocal microscope with white light. Roughness parameters obtained were: Ra, Rq, Rv, Rp, Rt, Rsk and Rku. The results were analysed using single-factor ANOVA and Student-Neuman-Keuls (p<0.05) tests. RESULTS: Certain and Hikelt obtained the highest Ra and Rq scores, followed by Tissue Level. Interna and SPI obtained lower scores, and MG-InHex obtained the lowest score. Rv scores followed the same trend. Certain obtained the highest Rp score, followed by SPI and Hikelt, then Interna and Tissue Level. MG-InHex obtained the lowest scores. Certain obtained the highest Rt score, followed by Interna and Hikelt, then SPI and Tissue Level. The lowest scores were for MG-InHex. Rsk was negative (punctured surface) in the MG-InHex, SPI and Tissue Level systems, and positive (pointed surface) in the other systems. Rku was higher than 3 (Leptokurtic) in Tissue Level, Interna, MG-InHex and SPI, and lower than 3 (Platykurtic) in Certain and Hikelt. CONCLUSIONS: The type of implant determines surface topography, and there are differences in the roughness parameters of the various makes of implants for clinical use.

Results of the ROADSTER multicenter trial of transcarotid stenting with dynamic flow reversal.

OBJECTIVE: This report presents the 30-day results of the Safety and Efficacy Study for Reverse Flow Used During Carotid Artery Stenting Procedure (ROADSTER) multicenter trial and evaluates the safety and efficacy of ENROUTE Transcarotid NPS (Silk Road Medical Inc, Sunnyvale, Calif), a novel transcarotid neuroprotection system that provides direct surgical common carotid access and cerebral embolic protection via high-rate flow reversal during carotid artery stenting (CAS). METHODS: A prospective, single-arm, multicenter clinical trial was performed to evaluate the use of the ENROUTE Transcarotid NPS during CAS procedures performed in patients considered to be at high risk for complications from carotid endarterectomy. Symptomatic patients with ≥50% stenosis and asymptomatic patients with ≥70% stenosis were eligible to be treated with any U.S. Food and Drug Administration-approved carotid artery stent. The primary end point was the composite of all stroke, myocardial infarction (MI), and death at 30 days postprocedure as defined in the Food and Drug Administration-approved study protocol. Secondary end points included cranial nerve injury; 30-day stroke, death, stroke/death, and MI; acute device, technical, and procedural success; and access site complications. All major adverse events were adjudicated by an independent clinical events committee. RESULTS: Between November 2012 and July 2014, 208 patients were enrolled at 18 sites. Sixty-seven patients were enrolled as lead-in cases, and 141 were enrolled in the pivotal phase. In the pivotal cohort, 26% were symptomatic and 75% were asymptomatic. Acute device and technical success were 99% (140 of 141). By hierarchical analysis, the all-stroke rate in the pivotal group was 1.4% (2 of 141), stroke and death was 2.8% (4 of 141), and stroke, death and MI was 3.5% (5 of 141). One patient (0.7%) experienced postoperative hoarseness from potential Xth cranial nerve injury, which completely resolved at the 6-month follow-up visit. CONCLUSIONS: The results of the ROADSTER trial demonstrate that the use of the ENROUTE Transcarotid NPS is safe and effective at preventing stroke during CAS. The overall stroke rate of 1.4% is the lowest reported to date for any prospective, multicenter clinical trial of CAS.

The impact of diabetes-related complications on healthcare costs: new results from the UKPDS (UKPDS 84).

AIMS: To estimate the immediate and long-term inpatient and non-inpatient costs for Type 2 diabetes-related complications. METHODS: The costs of all consultations, visits, admissions and procedures associated with diabetes-related complications during UK Prospective Diabetes Study post-trial monitoring in the period 1997-2007 were estimated using hospitalization records for 2791 patients in England and resource use questionnaires that were administered to 3589 patients across the UK. RESULTS: The estimated (95% CI) inpatient care costs (in 2012 pounds sterling) in the event year for the example of a 60-year-old man were: non-fatal ischaemic heart disease £9767 (£7038-£12 696); amputation £9546 (£6416-£13 463); non-fatal stroke £6805 (£3856-£10 278); non-fatal myocardial infarction £6379 (£4290-£8339); fatal stroke £3954 (£2012-£6428); fatal ischaemic heart disease £3766 (£746-£5512); heart failure £3191 (£1678-4903); fatal myocardial infarction £1521 (£647-£2670); and blindness in one eye £1355 (£415-£2655). In subsequent years, estimated (95% CI) costs ranged from £1792 (£1060-£2943) for amputations to £453 (£315-£691) for blindness in one eye. Costs of non-inpatient healthcare in the event year were: amputation £2699 (£1409-£4126); blindness in one eye £1790 (£878-£3056); non-fatal stroke £1019 (£770-£1499); nonfatal myocardial infarction £1963 (£794-£1157); heart failure £979 (£708-£1344); non-fatal ischaemic heart disease £864 (£718-£1014); and cataract extraction £700 (£619-£780). In each subsequent year, non-inpatient costs ranged from £1611 (£1193-£2116) for amputations to £654 (£572-£799) for ischaemic heart disease. CONCLUSIONS: Diabetic complications are associated with substantial immediate and long-term healthcare costs. Our comprehensive new estimates of these costs, derived from detailed recent UK Prospective Diabetes Study post-trial data, should aid researchers and health policy analyses.

Effect of root planing on surface topography: an in-vivo randomized experimental trial.

BACKGROUND AND OBJECTIVE: The root surface topography exerts a major influence on clinical attachment and bacterial recolonization after root planing. In-vitro topographic studies have yielded variable results, and clinical studies are necessary to compare root surface topography after planing with current ultrasonic devices and with traditional manual instrumentation. The aim of this study was to compare the topography of untreated single-rooted teeth planed in vivo with a curette, a piezoelectric ultrasonic (PU) scraper or a vertically oscillating ultrasonic (VOU) scraper. MATERIAL AND METHODS: In a randomized experimental trial of 19 patients, 44 single-rooted teeth were randomly assigned to one of four groups for: no treatment; manual root planing with a curette; root planing with a PU scraper; or root planing with a VOU scraper. Post-treatment, the teeth were extracted and their topography was analyzed in 124 observations with white-light confocal microscopy, measuring the roughness parameters arithmetic average height, root-mean-square roughness, maximum height of peaks, maximum depth of valleys, absolute height, skewness and kurtosis. RESULTS: The roughness values arithmetic average height and root-mean-square roughness were similar after each treatment and lower than after no treatment ( p < 0.05). Absolute height was lower in the VOU group than in the untreated ( p = 0.0026) and PU (p = 0.045) groups. Surface morphology was similar after the three treatments and was less irregular than in the untreated group. Values for the remaining roughness parameters were similar among all treatment groups ( p > 0.05). CONCLUSION: Both ultrasonic devices reduce the roughness, producing a similar topography to that observed after manual instrumentation with a curette, to which they appear to represent a valid alternative.

Topical and intravenous tranexamic acid reduce blood loss compared to routine hemostasis in total knee arthroplasty: a multicenter, randomized, controlled trial.

INTRODUCTION: Tranexamic acid (TXA) is becoming widely used in orthopedic surgery to reduce blood loss and transfusion requirements, but consensus is lacking regarding the optimal route and dose of administration. The aim of this study was to compare the efficacy and safety of topical and intravenous routes of TXA with routine hemostasis in patients undergoing primary total knee arthroplasty (TKA). MATERIALS AND METHODS: We performed a randomized, multicenter, parallel, open-label clinical trial in adult patients undergoing primary TKA. Patients were divided into three groups of 50 patients each: Group 1 received 1 g topical TXA, Group 2 received 2 g intravenous TXA, and Group 3 (control group) had routine hemostasis. The primary outcome was total blood loss. Secondary outcomes were hidden blood loss, blood collected in drains, transfusion rate, number of blood units transfused, adverse events, and mortality. RESULTS: One hundred and fifty patients were included. Total blood loss was 1021.57 (481.09) mL in Group 1, 817.54 (324.82) mL in Group 2 and 1415.72 (595.11) mL in Group 3 (control group). Differences in total blood loss between the TXA groups and the control group were clinically and statistically significant (p < 0.001). In an exploratory analysis differences between the two TXA groups were not statistically significant (p = 0.073) Seventeen patients were transfused. Transfusion requirements were significantly higher in Group 3 (p = 0.005). No significant differences were found between groups regarding adverse events. CONCLUSION: We found that 1 g of topical TXA and 2 g of intravenous TXA were both safe strategies and more effective than routine hemostasis to reduce blood loss and transfusion requirements after primary TKA. LEVEL OF EVIDENCE: I.

Regional differences in the frequency of the c.985A>G ACADM mutation: findings from a meta-regression of genotyping and screening studies.

Several countries include medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, a rare autosomal recessive disease, in their newborn screening programmes despite prevalence uncertainty. We estimated the frequency of its most common mutation, c.985A>G, tested for regional differences and compared screening and genotype frequencies. We identified 43 studies reporting the frequency of c.985A>G over 10 million individuals, and pooled frequency data using a novel Bayesian approach. We found significant variation in the frequency of the mutation across regions supporting a reported founder effect. The proportion of c.985A>G homozygotes was highest in Western Europe with 4.1 (95%CI: 2.8-5.6) per 100,000 individuals, then the New World (3.2, 95%CI: 2.0-4.7), Southern (1.2, 95%CI: 0.6-2.0) and Eastern European regions (0.9, 95%CI: 0.5-1.7). No cases with the mutation were identified in Asian and Middle Eastern regions. Significant differences were found in some countries between the genotype and screening allele frequency of c.985A>G. Our predictions could inform the frequency of the mutation by region and our approach could apply to other genetic conditions.