What remains after the money ends? Evidence on whether admission reductions continued following the largest health and social care integration programme in England.

We study the long-term effects on hospital activity of a three-year national integration programme. We use administrative data spanning from 24 months before to 22 months after the programme, to estimate the effect of programme discontinuation using difference-in-differences method. Our results show that after programme discontinuation, emergency admissions were slower to increase in Vanguard compared to non-Vanguard sites. These effects were heterogeneous across sites, with greater reductions in care home Vanguard sites and concentrated among the older population. Care home Vanguards showed significant reductions beginning early in the programme but falling away more rapidly after programme discontinuation. Moreover, there were greater reductions for sites performing poorly before the programme. Overall, this suggests the effects of the integration programme might have been lagged but transitory, and more reliant on continued programme support.

How Neurotech Start-Ups Envision Ethical Futures: Demarcation, Deferral, Delegation.

Like many ethics debates surrounding emerging technologies, neuroethics is increasingly concerned with the private sector. Here, entrepreneurial visions and claims of how neurotechnology innovation will revolutionize society-from brain-computer-interfaces to neural enhancement and cognitive phenotyping-are confronted with public and policy concerns about the risks and ethical challenges related to such innovations. But while neuroethics frameworks have a longer track record in public sector research such as the U.S. BRAIN Initiative, much less is known about how businesses-and especially start-ups-address ethics in tech development. In this paper, we investigate how actors in the field frame and enact ethics as part of their innovative R&D processes and business models. Drawing on an empirical case study on direct-to-consumer (DTC) neurotechnology start-ups, we find that actors engage in careful boundary-work to anticipate and address public critique of their technologies, which allows them to delineate a manageable scope of their ethics integration. In particular, boundaries are drawn around four areas: the technology's actual capability, purpose, safety and evidence-base. By drawing such lines of demarcation, we suggest that start-ups make their visions of ethical neurotechnology in society more acceptable, plausible and desirable, favoring their innovations while at the same time assigning discrete responsibilities for ethics. These visions establish a link from the present into the future, mobilizing the latter as promissory place where a technology's benefits will materialize and to which certain ethical issues can be deferred. In turn, the present is constructed as a moment in which ethical engagement could be delegated to permissive regulatory standards and scientific authority. Our empirical tracing of the construction of 'ethical realities' in and by start-ups offers new inroads for ethics research and governance in tech industries beyond neurotechnology.

No component loosening of a cementless deep dish rotating platform knee at a 5-year follow-up.

PURPOSE: Cemented fixation remains the gold standard in total knee arthroplasty. With an increasing number of younger patients undergoing total knee arthroplasty and a growing patient population demanding higher physical activity, a rising interest in discussion of cementless fixation is notable. The current scientific literature does not give a clear recommendation for or against uncemented total knee arthroplasty. The purpose of this study was the investigation of the 5-year clinical and radiographic outcomes of a cementless deep-dish rotating platform implant. METHODS: A total of 91 primary cementless total knee arthroplasties were included in this single-centre prospective observational study. The primary outcome was revision rate due to aseptic component loosening. Further outcome measures were assessment of the of the radiographic outcome as well as the clinical outcome based on Range of Motion and scores such as American Knee Society Score, Oxford Knee Score, Knee Injury and Osteoarthritis Outcome Score and European Quality of Life 5 Dimension 3 Level at a follow-up of 5 years. RESULTS: Mean age of the study population was 67.3 ± 6.6 years with 49.5% of the participants being female. Aseptic component loosening occurred in none of the patients. Implant survival with revision for any reason as endpoint was 97.8% (95% CI 100-96%) and 95.6% (95% CI 100-94%) with reoperation of any cause as endpoint. Radiolucent lines were detected in a total of eight cases (8.8%) and disappeared within the first year after surgery in five cases. Total Range of Motion improved significantly from 106° ± 15° preoperatively to 118° ± 10° at final FU (p < 0.001). All investigated scores improved significantly after total knee arthroplasty. CONCLUSION: The results of this study reveal excellent mid-term performance of a cementless deep dish rotating platform total knee implant, with no component loosening, very low overall revision rate, only temporarily present radiolucent lines in a minority of patients and excellent clinical results. Therefore, cementless total knee arthroplasty is an appropriate treatment option for patients with severe osteoarthritis of the knee. LEVEL OF EVIDENCE: Level II (prospective cohort study).

The importance of selecting a cruciate-retaining total knee prosthesis for a patient with a large physiological posterior tibial slope: a case report.

For Japanese individuals, deep bending is inevitable in their daily lives, such as during seiza sitting and kneeling. Thus, achieving a good post-operative range of motion is an important factor in improving patient satisfaction. Even normal knees often have a posterior tibial slope of more than 10°. We report the case of a 76-year-old woman who underwent proximal tibial osteotomy at 8° with the Vanguard Knee cruciate retaining total knee arthroplasty (TKA) system. She required the revision TKA 10 years later due to ultra-high-molecular-weight polyethylene wear and breakage of the posteromedial tibial component.

Locking mechanism failure between tibial baseplate and polyethylene insert in cruciate retaining total knee arthroplasty.

We describe a case of total knee arthroplasty performed with one type of cruciate retaining knee prosthesis (Vanguard CR, Zimmer Biomet), wherein failure of locking mechanism occurred between the tibial baseplate and the polyethylene insert 10 months after initial surgery. While there are very few case reports in literature describing such locking mechanism failure, all of these have been in constrained and posterior stabilized knees. This case, to the best of our knowledge is the first such case seen with a cruciate retaining knee design. A 73-year old lady, having undergone left total knee arthroplasty with the above-mentioned prosthesis, presented 10 months after the index surgery with a 3-week history of worsening knee pain and medially protruding hardware. She mentioned an episode of minor twisting of her knee after which she developed pain and swelling over the medial aspect, and was found to have the locking bar backed out on X-rays. She underwent revision surgery, wherein the locking bar was found to have buttonholed through the medial capsule. She underwent polyethylene liner exchange, with a new locking bar. There was no evidence of infection. Her symptoms fully settled following revision surgery.

Vanguard is a Glucose Deprivation-Responsive Long Non-Coding RNA Essential for Chromatin Remodeling-Reliant DNA Repair.

Glucose metabolism contributes to DNA damage response pathways by regulating chromatin remodeling, double-strand break (DSB) repair, and redox homeostasis, although the underlying mechanisms are not fully established. Here, a previously uncharacterized long non-coding RNA is revealed that is call Vanguard which acts to promote HMGB1-dependent DNA repair in association with changes in global chromatin accessibility. Vanguard expression is maintained in cancer cells by SP1-dependent transcription according to glucose availability and cellular adenosine triphosphate (ATP) levels. Vanguard promotes complex formation between HMGB1 and HDAC1, with the resulting deacetylation of HMGB1 serving to maintain its nuclear localization and DSB repair function. However, Vanguard downregulation under glucose limiting conditions promotes HMGB1 translocation from the nucleus, increasing DNA damage, and compromising cancer cell growth and viability. Moreover, Vanguard silencing increases the effectiveness of poly (ADP-ribose) polymerase inhibitors against breast cancer cells with wild-type breast cancer gene-1 status, suggesting Vanguard as a potential therapeutic target.

Cross-Neutralization of Vanguard C4 Vaccine Against Australian Isolates of Canine Parvovirus Variants CPV-2a, CPV-2b, and CPV-2c.

Canine parvovirus type 2 (CPV-2) remains one of the most significant viral pathogens in dogs in Australia and worldwide despite the availability of safe and effective CPV vaccines. At least three different variants of CPV-2 have emerged and spread all around the world, namely CPV-2a, CPV-2b, and CPV-2c. The ability of the current vaccines containing either original CPV-2 type or CPV-2b variant to cross protect the heterologous variants has been well demonstrated in laboratory studies, despite some concerns regarding the vaccine efficacy against the emerging variants. Vanguard®, a series of multivalent vaccines, has been in the market for a considerable period of time and demonstrated to provide efficacy against all three types of CPV variants CPV-2a, CPV-2b, and CPV-2c. The purpose of this study was to evaluate the ability of the recently registered Vanguard C4 vaccine to induce cross-neutralizing antibodies against the Australian isolates of CPV-2a, CPV-2b, and CPV-2c variants. Blood samples collected from dogs vaccinated with Vanguard C4 were analyzed by virus neutralizing assays developed for each of three CPV variants. The results of the study demonstrated that Vanguard vaccine induced cross-neutralizing antibodies against the Australian isolates of CPV-2a, CPV-2b, and CPV-2c, thus offering cross protection against all three Australian CPV variants.

Hybrid Cementation Technique Using the New Modular System for Aseptic Knee Arthroplasty Revision Surgery.

Background: To evaluate the clinical and radiological outcomes of aseptic revision of total knee arthroplasty (TKA) using the Vanguard 360 Revision Knee System with the hybrid cementation technique. Methods: Between January 2014 and October 2016, nineteen aseptic revision TKAs were carried out with the Vanguard 360 Revision Knee System (Zimmer-Biomet, Warsaw, IN, USA) performed by two different surgeons. The patients were evaluated clinically and radiographically at one, six, and twelve months after surgery and yearly thereafter. Functional outcomes were assessed according to the range of motion (ROM), knee society knee score (KSKS) and knee society function score (KSFS). Radiological evaluations were performed using the hip-knee-ankle angle (HKA), weight-bearing anteroposterior view, latero-lateral view, Rosenberg x-rays of the knee and skyline patellar x-rays. A triple-phase technetium bone scan was performed on all the patients complaining of knee pain after one year from surgery. Results: Clinical and radiological results including KSKS, KSFS, ROM and HKA angle improved after revision of TKA with a statistically significant difference (p <0.05). There were seven revisions of the CCK prosthesis due to persistent pain. Conclusion: Patients who underwent revision of TKA using the Vanguard 360 with the hybrid cementation technique had a failure rate of 36.8% at a mean time of 29 months due to aseptic loosening. Further studies are required to analyse the role of cementation in detail to prevent this complication.

Effects of nonoxynol-9 (N-9) on sperm functions: systematic review and meta-analysis.

Objective: To summarize the currently available phase I and II clinical trials of the effects of nonoxynol-9 (N-9) on human sperm structure and functions. Methods: A systematic review and meta-analysis aiming to evaluate the spermicidal activity of N-9 on motility, was conducted in PubMed, EMBASE, and Cochrane databases by 10 March 2021. The counted numbers of progressive motile (PR) sperm in cervical mucus and the vanguard sperm penetration distances were analyzed. Other effects on sperm structures and physiological activities were reviewed as well. Results: In the pooled results, percentages or counted numbers of PR sperm decreased after the treatment of N-9. Vanguard sperm penetration distance was shortened in treated groups. N-9 has been confirmed to damage the structures of sperm, as well as other organelles like acrosome and mitochondria. The physiological activities such as generation of reactive oxygen species, superoxide dismutase activity, acrosin activity, and hemizona binding were all inhibited in the reviewed studies. Conclusions: N-9 has several impacts on sperm owing to its potency in reducing sperm motility and cervical mucus penetration, as well as other functional competencies. Lay summary: Nonoxynol-9 (N-9) has been used worldwide as a spermicide to kill sperm for more than 60 years but can cause side effects including vaginal irritation and can increase the rate of contraceptive failure. A detailed analysis of published literature aiming to evaluate the spermicidal activity of N-9 on sperm was carried out. In the pooled results, N-9 reduced the number of active sperm and the distance they traveled. It also caused damage to the structures of sperm and to the way the sperm acted and interacted with the egg. In conclusion, N-9 impacts on sperm in a number of ways that lead to sperm death and dysfunction.

IT Evaluation of Foundation Healthcare Group NHS Vanguard programme: IT simultaneously an enabler and a rate limiting factor.

The goal of the Foundation Healthcare Group (FHG) Vanguard model was to develop a sustainable local hospital model between two National Health Service (NHS) Trusts (a London Teaching Hospital Trust and a District General Hospital Trust) that makes best use of scarce resources and can be replicated across the NHS, UK. The aim of this study was to evaluate the provision, use, and implementation of the IT infrastructure based on qualitative interviews focused mainly on the perspectives of the IT staff and the clinicians' perspectives. METHODS: In total, 24 interview transcripts, along with 'Acute Care Collaboration' questionnaire responses, were analyzed using a thematic framework for IT infrastructure, sharing themes across the vascular, pediatric, and cardiovascular strands of the FHG programme. RESULTS: Findings indicated that Skype for Business had been an innovative and helpful development widely available to be used between the two Trusts. Clinicians initially reported lack of IT support and infrastructure expected at the outset for a national Vanguard project but later appreciated that remote access to most clinical applications including scans between the two Trusts became operational. The Local Care Record (LCR), an IT project was perceived to have been delivered successfully in South London. Shared technology reduced patient traveling time by providing locally based shared care. CONCLUSION: Lesson learnt is that ensuring patient benefit and priorities is a strong driver to implementation and one needs to identify IT rate-limiting steps at an early stage and on a regular basis and then focus on rapid implementation of solutions. In fact, future work may also assess how the IT infrastructure developed by FHG vanguard project might have helped/boosted the 'digital health' practice during the COVID-19 times. Spreading and scaling-up innovations from the Vanguard sites was the aspiration and challenge for system leaders. After COVID-19, the use of IT is scaled up and now, the challenges in the use of IT are much less compared to the pre-COVID-19 time when this project was evaluated.

Comparison of the impact of two national health and social care integration programmes on emergency hospital admissions.

BACKGROUND: Policy-makers expect that integration of health and social care will improve user and carer experience and reduce avoidable hospital use. [We] evaluate the impact on emergency hospital admissions of two large nationally-initiated service integration programmes in England: the Pioneer (November 2013 to March 2018) and Vanguard (January 2015 to March 2018) programmes. The latter had far greater financial and expert support from central agencies. METHODS: Of the 206 Clinical Commissioning Groups (CCGs) in England, 51(25%) were involved in the Pioneer programme only, 22(11%) were involved in the Vanguard programme only and 13(6%) were involved in both programmes. We used quasi-experimental methods to compare monthly counts of emergency admissions between four groups of CCGs, before and after the introduction of the two programmes. RESULTS: CCGs involved in the programmes had higher monthly hospital emergency admission rates than non-participants prior to their introduction [7.9 (95% CI:7.8-8.1) versus 7.5 (CI: 7.4-7.6) per 1000 population]. From 2013 to 2018, there was a 12% (95% CI:9.5-13.6%) increase in emergency admissions in CCGs not involved in either programme while emergency admissions in CCGs in the Pioneer and Vanguard programmes increased by 6.4% (95% CI: 3.8-9.0%) and 8.8% (95% CI:4.5-13.1%), respectively. CCGs involved in both initiatives experienced a smaller increase of 3.5% (95% CI:-0.3-7.2%). The slowdown largely occurred in the final year of both programmes. CONCLUSIONS: Health and social care integration programmes can mitigate but not prevent rises in emergency admissions over the longer-term. Greater financial and expert support from national agencies and involvement in multiple integration initiatives can have cumulative effects.

Contextual interference in children with brain lesions: a pilot study investigating blocked vs. random practice order of an upper limb robotic exergame.

INTRODUCTION: Evidence about contextual interference in children with brain lesions when practising motor tasks is lacking. Our main objective was to evaluate the feasibility of a randomised controlled trial (RCT) comparing blocked with random practice order of an upper limb robotic exergame to improve reaching in children with neuromotor disorders with a pilot trial. METHODS: We recruited children with brain lesions and impaired upper limb functions who underwent a 3-week schedule that consisted of baseline assessments, intervention period (participants were randomised to a blocked or random order group), and follow-up assessment. We evaluated ten feasibility criteria, including the practicability of the inclusion/exclusion criteria, recruitment rate, feasibility of randomisation, scheduling procedure, and the participants' programme adherence. RESULTS: The inclusion/exclusion criteria were not completely feasible as patients who were not able to perform the exergames were included. Twelve participants were recruited, and six datasets were used for analysis. The scheduling and randomisation procedures were generally feasible, but the procedure was only partially feasible for the participants, as some sessions were aborted due to lack of motivation and fatigue. CONCLUSION: An RCT following this study protocol is not feasible. We formulated suggestions for future studies that aim to investigate contextual interference as in this pilot study. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02443857 , registered on May 14, 2015.

IT Evaluation of Foundation Healthcare Group Vanguard Project.

The aim of the Foundation Healthcare Group (FHG) Vanguard model was to develop a sustainable local hospital model between two National Health Service (NHS) Trusts (a London Teaching Hospital Trust and a District General Hospital Trust) that makes best use of scarce resources and can be replicated across the NHS, UK. The aim of this study was to evaluate the provision, use and implementation of the IT infrastructure; based on qualitative interviews and focused mainly on the perspectives of the IT staff and the clinicians' perspectives. In total 24 interview transcripts, along with 'Acute Care Collaboration' questionnaire responses, were analysed using a thematic framework for IT infrastructure, sharing themes across the vascular, paediatric and cardiovascular strands of the FHG programme. Findings indicated that Skype for Business had been an innovative and helpful development widely available to be used between the two Trusts. Clinicians initially reported lack of IT support and infrastructure expected at the outset for a national Vanguard project, but later appreciated that remote access to most clinical applications between the two Trusts became operational. The Local Care Record (LCR), an IT project was perceived to have been delivered successfully in South London. Shared technology reduced patient travelling time by providing locally based shared care. Spreading and scaling-up innovations from the Vanguard sites was the aspiration and challenge for system leaders.

Investigating the nature and quality of locally commissioned evaluations of the NHS Vanguard programme: an evidence synthesis.

BACKGROUND: With innovation in service delivery increasingly viewed as crucial to the long-term sustainability of health systems, NHS England launched an ambitious new model of care (Vanguard) programme in 2015. Supported by a £350 million transformation fund, 50 Vanguard sites were to act as pilots for innovation in service delivery, to move quickly to change the way that services were delivered, breaking down barriers between sectors and improving the coordination and delivery of care. METHODS: As part of a national evaluation of the Vanguard programme, we conducted an evidence synthesis to assess the nature and quality of locally commissioned evaluations. With access to a secure, online hub used by the Vanguard and other integrated care initiatives, two researchers retrieved any documents from a locally commissioned evaluation for inclusion. All identified documents were downloaded and logged, and details of the evaluators, questions, methodological approaches and limitations in design and/or reporting were extracted. As included evaluations varied in nature and type, a narrative synthesis was undertaken. RESULTS: We identified a total of 115 separate reports relating to the locally commissioned evaluations. Five prominent issues relating to evaluation conduct were identified across included reports: use of logic models, number and type of evaluation questions posed, data sharing and information governance, methodological challenges and evaluation reporting in general. A combination of resource, data and time constraints means that evaluations often attempted to but did not fully address the wide range of questions posed by individual Vanguards. CONCLUSIONS: Significant investment was made in independent local evaluations of the Vanguard programme by NHS England. This synthesis represents the only comprehensive attempt to capture methodological learning and may serve as a key resource for researchers and policy-makers seeking to understand investigating large-scale system change, both within the NHS and internationally. PROSPERO (Registration number: CRD42017069282).

New integrated care models in England associated with small reduction in hospital admissions in longer-term: A difference-in-differences analysis.

Closer integration of health and social care services has become a cornerstone policy in many developed countries, but there is still debate over what population and service level is best to target. In England, the 2019 Long Term Plan for the National Health Service included a commitment to spread the integration prototypes piloted under the Vanguard `New Care Models' programme. The programme, running from 2015 to 2018, was one of the largest pilots in English history, covering around 9 % of the population. It was largely intended to design prototypes aimed at reducing hospital utilisation by moving specialist care out of hospital into the community and by fostering coordination of health, care and rehabilitation services for (i) the whole population ('population-based sites'), or (ii) care home residents ('care home sites'). We evaluate and compare the efficacy of the population-based and care home site integrated care models in reducing hospital utilisation. We use area-level monthly counts of emergency admissions and bed-days obtained from administrative data using a quasi-experimental difference-in-differences design. We found that Vanguard sites had higher hospital utilisation than non-participants in the pre-intervention period. In the post-intervention period, there is clear evidence of a substantial increase in emergency admissions among non-Vanguard sites. The Vanguard integrated care programme slowed the rise in emergency admissions, especially in care home sites and in the third and final year. There was no significant reduction in bed-days. In conclusion, integrated care policies should not be relied upon to make large reductions in hospital activity in the short-run, especially for population-based models.

Overall outcome after endovascular aneurysm repair with a first-generation stent graft (Vanguard): A 20-year single-center experience.

OBJECTIVE: The problems with first-generation stent grafts for endovascular aneurysm repair are well known, but their long-term outcome remains to be established. The purpose of the study was to characterize the outcome of patients treated for abdominal aortic aneurysm (AAA) with a first-generation stent graft, Vanguard (Boston Scientific, Natick, Mass), in a single academic center with a follow-up of up to 20 years. METHODS: There were 48 AAA patients electively treated with a Vanguard stent graft between February 1997 and November 1999. The patients were monitored annually until the end of 2018. The outcomes were overall survival and the number of graft-related complications and reinterventions. RESULTS: The mean age was 70 years (range, 54-85 years), and the mean follow-up was 107 months (range, 6-262 months). All stent grafts were successfully implanted, but 90% of the patients encountered graft-related complications during follow-up. The most common complications were endoleaks (type I, 27%; type II, 29%; type III, 31%), stent fracture (46%), graft thrombosis (31%), and migration (40%). A total of 40 (83%) patients required a secondary procedure during long-term follow-up. The endovascular method for treating the complication was successful in 73 (87%) of 84 cases. There were no primary conversions, but 10 patients (21%) required a late conversion. In five cases, the complications required relining with a newer device. There were four AAA ruptures (8.3%), two of them fatal. The cumulative overall survival rates were 94%, 69%, 33%, 15%, and 13% at 1 year, 5 years, 10 years, 15 years, and 20 years, respectively. CONCLUSIONS: The use of the Vanguard, a first-generation stent graft, was associated with multiple graft-related complications. However, these complications could mainly be treated by endovascular means. The Vanguard stent graft is a good example of how new technology can cause unpredictable problems that can magnify the workload and endanger the patient's well-being even decades after the initial procedure.

Complex programme evaluation of a 'new care model' vanguard: a shared commitment to quality improvement in an integrated health and care context.

NHS vanguards, under-pressure to perform, required better contracting and data management arrangements with evaluation teams, to ensure that integrated service outcomes could be reported effectively. This communication reflects the experience of evaluating an NHS vanguard and suggests how academic teams can improve capacity for complex programme evaluation of rapid improvements in integrated services. This should be based on a shared commitment to data collection and management. Also, robust knowledge exchange processes can enable systems change and sustainability. The identifying features of the particular site have been withheld.

Low complication rates in outpatient total knee arthroplasty.

PURPOSE: The primary purpose of this study is to report the incidence of complications associated with outpatient total knee arthroplasty (TKA). Secondarily, 2-year minimum outcomes are reported. METHODS: Between 2013 and 2016, 928 patients underwent 1143 outpatient TKAs with the Vanguard Complete Knee System (Zimmer Biomet, Warsaw, IN). Patients were selected for outpatient surgery if they were medically optimized without a failing organ system and had sufficient support at home. Overnight stays, medical complications and early perioperative complications were assessed in this entire cohort. Two-year minimum follow-up was available on 793 patients (978 knees). Patient records were analyzed for outcome measures and revisions. RESULTS: In 124 procedures, the patient stayed overnight for 23-h observation. Thirty-seven (3.2%) were for convenience reasons and 87 (7.6%) for medical observation. Heart disease and chronic obstructive pulmonary disease were associated with increased risk of overnight stay. Excluding manipulations, reoperation within 90 days occurred in eight (0.7%) knees. Patients with 2-year minimum follow-up had significant improvements in ROM, Knee Society Clinical, Functional and Pain scores (p < 0.005). Nine (0.8%) patients required revision. Manipulations were performed on 118 (10.3%) patients. The overall deep infection rate was 0.17% (2/1143). CONCLUSIONS: Outpatient TKA is safe for a large proportion of patients. Certain medical co-morbidities increase the risk of overnight stay. Patients had significant improvement in ROM and outcome scores with low revision rate. LEVEL OF EVIDENCE: III.

Advances in Platelet Subpopulation Research.

Although lacking a nucleus, platelets are increasingly recognized not only for their complexity, but also for their diversity. Some 50 years ago platelet subpopulations were characterized by size and density, and these characteristics were thought to reflect platelet aging. Since, our knowledge of platelet heterogeneity has grown to recognize that differences in platelet biochemistry and function exist. This includes the identification of vanguard and follower platelets, platelets with differing procoagulant ability including "COAT-platelets" which enhance procoagulant protein retention on their surface, and most recently, the identification of platelet subpopulations with a differential ability to generate and respond to nitric oxide. Hence, in this mini-review, we summarize the current knowledge of platelet subpopulation diversity focusing on their physical, biochemical, and functional heterogeneity. In addition, we review how platelet subpopulations may change between health and disease and how differences among platelets may influence response to anti-platelet therapy. Finally, we look forward and discuss some of the future directions and challenges for this growing field of platelet research.

A methodological survey on reporting of pilot and feasibility trials for physiotherapy interventions: a study protocol.

INTRODUCTION: Pilot and feasibility trials aim to test whether a full trial can be conducted or if any procedures must be changed for the full trial. Pilot trials must be reported in a transparent, accurate and complete way. In this report, we present a protocol for a methodological survey with the following aims: (1) to determine the percentage of physiotherapy trial reports which claim to be pilot or feasibility trials that evaluate feasibility, (2) to determine the aspect of feasibility evaluated in the primary objectives of the pilot or feasibility trials, (3) to describe the completeness of reporting of abstracts and full articles of pilot or feasibility trials using the Consolidated Standards of Reporting Trials (CONSORT) extension to randomised pilot and feasibility trials and (4) to investigate factors associated with completeness of reporting of pilot or feasibility trials. METHODS AND ANALYSIS: Reports of randomised controlled trials indexed in the Physiotherapy Evidence Database (PEDro) that claim to be pilot or feasibility trials and published in 2011-2017 will be included. Two independent reviewers will confirm eligibility and classify the aspect of feasibility being evaluated in the objectives of the included pilot or feasibility trials. Completeness of reporting of both the abstract and the full article will be evaluated using the CONSORT extension to randomised pilot and feasibility trials. The primary analysis will be a descriptive analysis about the reporting quality of abstracts and full texts of pilot and feasibility trials. We will use generalised estimating equation analysis to explore factors associated with completeness of reporting. ETHICS AND DISSEMINATION: The results of this study will be disseminated by presentation at conferences and will be submitted for publication in a peer-reviewed journal. Ethical approval is not necessary for this study.