Heterogeneity after harmonisation: A retrospective cohort study of bleeding and stroke risk after the introduction of direct oral anticoagulants in four Western European countries.

PURPOSE: Database heterogeneity can impact effect estimates. Harmonisation provided by common protocols and common data models (CDMs) can increase the validity of pharmacoepidemiologic research. In a case study measuring the changes in the safety and effectiveness of stroke prevention therapy after the introduction of direct oral anticoagulants (DOACs), we performed an international comparison. METHODS: Using data from Stockholm, Denmark, Scotland and Norway, harmonised with a common protocol and CDM, two calendar-based cohorts were created: 2012 and 2017. Patients with a diagnosis code of atrial fibrillation 5 years preceding the 1-year cohort window were included. DOAC, vitamin K antagonist and aspirin treatment were assessed in the 6 months prior to the start of each year while strokes and bleeds were assessed during the year. A Poisson regression generated incidence rate ratios (IRRs) to compare outcomes from 2017 to 2012 adjusted for changes in individual-level baseline characteristics. RESULTS: In 280 359 patients in the 2012 cohort and 356 779 in the 2017 cohort, treatment with OACs increased on average from 45% to 65%, while treatment with aspirin decreased from 30% to 10%. In all countries except Scotland, there were decreases in the risk of stroke and no changes in bleeding risk, after adjustment for changes in baseline characteristics. In Scotland, major bleeding (IRR 1.09, 95% confidence interval [CI] [1.00; 1.18]) and intracranial haemorrhage (IRR 1.31, 95% CI [1.13; 1.52]) increased from 2012 to 2017. CONCLUSIONS: Stroke prevention therapy improved from 2012 to 2017 with a corresponding reduction in stroke risk without increasing the risk of bleeding in all countries, except Scotland. The heterogeneity that remains after methodological harmonisation can be informative of the underlying population and database.

Sequence-Dependent Melting and Refolding Dynamics of RNA UNCG Tetraloops Using Temperature-Jump/Drop Infrared Spectroscopy.

Time-resolved temperature-jump/drop infrared (IR) spectroscopy has been used to measure the impact of stem base sequence on the melting and refolding dynamics of ribonucleic acid (RNA) tetraloops. A series of three 12-nucleotide RNA hairpin sequences were studied, each featuring a UACG tetraloop motif and a double-stranded stem containing four base pairs. In each case, the stem comprised three GC pairs plus a single AU base pair inserted at the closing point of the loop (RNAloop), in the middle of the stem (RNAmid), or at the stem terminus (RNAend). Results from analogous DNA tetraloop (TACG) sequences were also obtained. Inclusion of AU or AT base pairs in the stem leads to faster melting of the stem-loop structure compared to a stem sequence featuring four GC base pairs while refolding times were found to be slower, consistent with a general reduction in stem-loop stability caused by the AU/AT pair. Independent measurement of the dynamic timescales for melting and refolding of ring vibrational modes of guanine (GR) and adenine (AR) provided position-specific insight into hairpin dynamics. The GR-derived data showed that DNA sequences melted more quickly (0.5 ± 0.1 to 0.7 ± 0.1 µs at 70 °C) than analogous RNA sequences (4.3 ± 0.4 to 4.4 ± 0.3 µs at 70 °C). Position-sensitive data from the AR modes suggests that DNA hairpins begin melting from the terminal end of the stem toward the loop while RNA sequences begin melting from the loop. Refolding timescales for both RNA and DNA hairpins were found to be similar (250 ± 50 µs at 70 °C) except for RNAend and DNAloop which refolded much more slowly (746 ± 36 and 430 ± 31 µs, respectively), showing that the refolding pathway is significantly impaired by the placement of AU/AT pairs at different points in the stem. We conclude that conformational changes of analogous pairs of RNA and DNA tetraloops proceed by different mechanisms.

Post-mortem computed tomography in the investigation of conflict and terrorist related deaths: UK military experience of developing a multidisciplinary service.

This paper discusses the introduction, development and utility of post-mortem imaging relating specifically to conflict-related and terrorist-related deaths and considers the use of computed tomography (CT) in the investigations. We demonstrate how a multi-disciplinary approach involving direct communication between forensic pathologist and radiologist can maximise evidential yield, reduce the need for unnecessary dissection and further our understanding of such injuries. This summarises our shared experience of hundreds of cases, each having been individually discussed and reviewed, and has helped shape our understanding of conflict injury as well as contributing to the development of mitigation strategies and adaptations to protective equipment. A series of clinical cases are presented to demonstrate some of the strengths and weaknesses of the process.

Measuring RNA UNCG Tetraloop Refolding Dynamics Using Temperature-Jump/Drop Infrared Spectroscopy.

Determining the structural dynamics of RNA and DNA is essential to understanding their cellular function, but direct measurement of strand association or folding remains experimentally challenging. Here we illustrate a temperature-jump/drop method able to reveal refolding dynamics. Time-resolved temperature-jump/drop infrared spectroscopy is used to measure the melting and refolding dynamics of a 12-nucleotide RNA sequence comprising a UACG tetraloop and a four-base-pair double-stranded GC stem, comparing them to an equivalent DNA (TACG) sequence. Stem-loop melting occurred an order of magnitude more slowly in RNA than DNA (6.0 ± 0.1 µs versus 0.8 ± 0.1 µs at 70 °C). In contrast, the refolding dynamics of both sequences occurred on similar time scales (200 µs). While the melting and refolding dynamics of RNA and DNA hairpins both followed Arrhenius temperature dependences, refolding was characterized by an apparent negative activation energy, consistent with a mechanism involving multiple misfolded intermediates prior to zipping of the stem base pairs.

The enhanced recovery after surgery (ERAS) Greenie Board: a Navy-inspired quality improvement tool.

The United States Navy uses a visual feedback system for pilots, named 'the Greenie Board', to improve flight manoeuvres on aircraft carriers. Given that increased compliance with enhanced recovery after surgery protocols reduces postoperative complications, we decided to apply a similar feedback system to our institutional enhanced recovery programme. We undertook a prospective 12-month audit of 194 patients assigned to our enhanced recovery programme and evaluated adherence to the anaesthesia-related components of our protocol, before and after implementing a Greenie Board. A compliance score was calculated by summing points for adherence to: intra-operative antibiotic prophylaxis; temperature management; goal-directed intravenous fluid therapy; postoperative nausea and vomiting prophylaxis; and postoperative fluid restriction. The score for each patient was then colour-coded and anonymously displayed for each anaesthetist on a Greenie Board within the operating theatre suite. Protocol adherence improved significantly following introduction, with 'Green' scores (acceptable compliance) increasing from 33% to 72% of patients (p < 0.0001). The greatest improvement was seen with anti-emetic prophylaxis (49% to 70%, p = 0.004) with a consequent reduction in postoperative nausea and vomiting (OR 0.42, 95% CI 0.19-0.88, p = 0.021). We did not observe a decrease in other postoperative complications nor hospital length of stay. We conclude that this US Navy-inspired feedback system is an easily implemented, low-cost quality improvement tool that significantly improved adherence to intra-operative components of our enhanced recovery protocol. The system lends itself to global scaling to drive quality improvement in healthcare delivery and would be suited to institutions without electronic medical records, including low-resource countries.

An overview of systematic reviews on the public health consequences of social isolation and loneliness.

OBJECTIVES: Social isolation and loneliness have been associated with ill health and are common in the developed world. A clear understanding of their implications for morbidity and mortality is needed to gauge the extent of the associated public health challenge and the potential benefit of intervention. STUDY DESIGN: A systematic review of systematic reviews (systematic overview) was undertaken to determine the wider consequences of social isolation and loneliness, identify any differences between the two, determine differences from findings of non-systematic reviews and to clarify the direction of causality. METHODS: Eight databases were searched from 1950 to 2016 for English language reviews covering social isolation and loneliness but not solely social support. Suitability for inclusion was determined by two or more reviewers, the methodological quality of included systematic reviews assessed using the a measurement tool to assess systematic reviews (AMSTAR) checklist and the quality of evidence within these reviews using the grading of recommendations, assessment, development and evaluations (GRADE) approach. Non-systematic reviews were sought for a comparison of findings but not included in the primary narrative synthesis. RESULTS: Forty systematic reviews of mainly observational studies were identified, largely from the developed world. Meta-analyses have identified a significant association between social isolation and loneliness with increased all-cause mortality and social isolation with cardiovascular disease. Narrative systematic reviews suggest associations with poorer mental health outcomes, with less strong evidence for behavioural and other physical health outcomes. No reviews were identified for wider socio-economic or developmental outcomes. CONCLUSIONS: This systematic overview highlights that there is consistent evidence linking social isolation and loneliness to worse cardiovascular and mental health outcomes. The role of social isolation and loneliness in other conditions and their socio-economic consequences is less clear. More research is needed on associations with cancer, health behaviours, and the impact across the life course and wider socio-economic consequences. Policy makers and health and local government commissioners should consider social isolation and loneliness as important upstream factors impacting on morbidity and mortality due to their effects on cardiovascular and mental health. Prevention strategies should therefore be developed across the public and voluntary sectors, using an asset-based approach.

Does preliminary optimisation of an anatomically correct skull-brain model using simple simulants produce clinically realistic ballistic injury fracture patterns?

Ballistic head injury remains a significant threat to military personnel. Studying such injuries requires a model that can be used with a military helmet. This paper describes further work on a skull-brain model using skulls made from three different polyurethane plastics and a series of skull 'fills' to simulate brain (3, 5, 7 and 10% gelatine by mass and PermaGel™). The models were subjected to ballistic impact from 7.62 × 39 mm mild steel core bullets. The first part of the work compares the different polyurethanes (mean bullet muzzle velocity of 708 m/s), and the second part compares the different fills (mean bullet muzzle velocity of 680 m/s). The impact events were filmed using high speed cameras. The resulting fracture patterns in the skulls were reviewed and scored by five clinicians experienced in assessing penetrating head injury. In over half of the models, one or more assessors felt aspects of the fracture pattern were close to real injury. Limitations of the model include the skull being manufactured in two parts and the lack of a realistic skin layer. Further work is ongoing to address these.

Post-viraemic detection of bovine ephemeral fever virus by use of autogenous lymphoid tissue-derived bovine primary cell cultures.

BACKGROUND: The potential tissue replication sites and specific cell types that support in vivo virus survival beyond the acute phase of bovine ephemeral fever virus (BEFV) infection have not been fully defined in cattle. To clarify the knowledge gap, tissue specimens were tested after collection from an adult steer necropsied 1 week after acute BEF. CASE REPORT: Significant necropsy findings included fibrinoproliferative synovitis in the stifle joints and fibrin clot-laden fluid in serous body cavities. Moderate numbers of infiltrating neutrophils were demonstrated in sections of the prefemoral lymph nodes and haemal node, and lymphoid hyperplasia in the spleen, haemal node and prefemoral lymph nodes. Viral RNA was detected by qRT-PCR in fresh spleen, haemal node, prefemoral lymph node, synovial fluid and in several spleen-derived cell cultures. BEFV was isolated from autogenously derived splenic primary cell cultures 6 days after cessation of viraemia, and characteristic bullet-shaped virions were confirmed by electron microscopy of an ultrathin haemal node section. In sections of the spleen, haemal node and other tissues, immunohistochemistry demonstrated BEFV antigens that were intracellularly associated with probable histiocytic cells. CONCLUSION: BEFV has preferential tropism for bovine lymphoid tissues and the spleen and haemal node may be potential sites for post-viraemic virus replication.

Using experimental and computational energy equilibration to understand hierarchical self-assembly of Fmoc-dipeptide amphiphiles.

Despite progress, a fundamental understanding of the relationships between the molecular structure and self-assembly configuration of Fmoc-dipeptides is still in its infancy. In this work, we provide a combined experimental and computational approach that makes use of free energy equilibration of a number of related Fmoc-dipeptides to arrive at an atomistic model of Fmoc-threonine-phenylalanine-amide (Fmoc-TF-NH2) which forms twisted fibres. By using dynamic peptide libraries where closely related dipeptide sequences are dynamically exchanged to eventually favour the formation of the thermodynamically most stable configuration, the relative importance of C-terminus modifications (amide versus methyl ester) and contributions of aliphatic versus aromatic amino acids (phenylalanine F vs. leucine L) is determined (F > L and NH2 > OMe). The approach enables a comparative interpretation of spectroscopic data, which can then be used to aid the construction of the atomistic model of the most stable structure (Fmoc-TF-NH2). The comparison of the relative stabilities of the models using molecular dynamic simulations and the correlation with experimental data using dynamic peptide libraries and a range of spectroscopy methods (FTIR, CD, fluorescence) allow for the determination of the nanostructure with atomistic resolution. The final model obtained through this process is able to reproduce the experimentally observed formation of intertwining fibres for Fmoc-TF-NH2, providing information of the interactions involved in the hierarchical supramolecular self-assembly. The developed methodology and approach should be of general use for the characterization of supramolecular structures.

Viral neurotropism, peripheral neuropathy and other morphological abnormalities in bovine ephemeral fever virus-infected downer cattle.

OBJECTIVE: This study assessed the neurotropism of bovine ephemeral fever (BEF) virus (BEFV) and described histomorphological abnormalities of the brain, spinal cord and peripheral nerves that may causally contribute to paresis or paralysis in BEF. METHODS: Four paralysed and six asymptomatic but virus-infected cattle were monitored, and blood and serum samples screened by qRT-PCR, virus isolation and neutralisation tests. Fresh brain, spinal cord, peripheral nerve and other tissues were qRT-PCR-tested for viral RNA, while formalin-fixed specimens were processed routinely and immunohistochemically evaluated for histomorphological abnormalities and viral antigen distribution, respectively. RESULTS: The neurotropism of BEFV was immunohistochemically confirmed in the brain and peripheral nerves and peripheral neuropathy was demonstrated in three paralysed but not the six aneurological but virus-infected animals. Wallerian degeneration (WD) was present in the ventral funicular white matter of the lumbar spinal cord of a paralysed steer and in cervical and thoracic spinal cord segments of three paralysed animals. Although no spinal cord lesions were seen in the steer euthanased within 7 days of illness, peripheral neuropathy was present and more severe in nerves of the brachial plexuses than in the gluteal or fibular nerves. The only steer with WD in the lumbar spinal cord also showed intrahistiocytic cell viral antigen that was spatially distributed within areas of moderate brain stem encephalitis. CONCLUSION: The data confirmed neurotropism of BEFV in cattle and documented histomorphological abnormalities in peripheral nerves and brain which, together with spinal cord lesions, may contribute to chronic paralysis in BEFV-infected downer cattle.

Redesign and commissioning of sexual health services in England - a qualitative study.

OBJECTIVES: Responsibility for the commissioning of sexual and reproductive health (SRH) services transferred from the National Health Service to local authorities in England in 2013. This transfer prompted many local authorities to undertake new procurements of these SRH services. This study was undertaken to capture some of the lessons learnt in order to inform future commissioning and system redesign. STUDY DESIGN: A qualitative study was carried out involving semi-structured interviews. METHODS: Interviews were conducted with 13 local authority sexual health commissioners in Yorkshire and the Humber from 11 interviews. Thematic analysis was used to identify themes from transcripts of the interviews with the 13 participants. RESULTS: Key themes identified were as follows: the challenge and complexity to those new to clinical commissioning; the prerequisites of robust infrastructural inputs to undertake the process, including technical expertise, a dependable project team, with clarity over the timescales and the budget; the requirement for good governance, stakeholder engagement and successful management of relationships with the latter; and the need to focus on the outcomes, aiming for value for money and improved system performance. CONCLUSIONS: Several key issues emerged from our study that significantly influenced the outcome of the redesign and commissioning process for sexual health services. An adapted model of the Donabedian evaluation framework was developed to provide a tool to inform future system redesign. Our model helps identify the key determinants for successful redesign in this context which is essential to both mitigate potential risks and maximize the likelihood of successful outcomes. Our model may have wider applications.

Evidence-based guidelines for treating bipolar disorder: Revised third edition recommendations from the British Association for Psychopharmacology.

The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder. The third version is based explicitly on the available evidence and presented, like previous Clinical Practice Guidelines, as recommendations to aid clinical decision making for practitioners: it may also serve as a source of information for patients and carers, and assist audit. The recommendations are presented together with a more detailed review of the corresponding evidence. A consensus meeting, involving experts in bipolar disorder and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from these participants. The best evidence from randomized controlled trials and, where available, observational studies employing quasi-experimental designs was used to evaluate treatment options. The strength of recommendations has been described using the GRADE approach. The guidelines cover the diagnosis of bipolar disorder, clinical management, and strategies for the use of medicines in short-term treatment of episodes, relapse prevention and stopping treatment. The use of medication is integrated with a coherent approach to psychoeducation and behaviour change.

Kinetics of selected plasma cytokines during innate-adaptive immune response transition in adult cattle infected with the bovine ephemeral fever virus.

While virus neutralizing antibodies are known to be variably protective against bovine ephemeral fever (BEF) virus (BEFV) infections, the cytokine events that mediate the nascent adaptive immune response have not been defined in cattle. This study determined the plasma kinetics of IL-2, IFN-γ, IL-6, and IL-10 during the period of innate-immune response transition and evaluated the relationship between the virus neutralizing antibody response and viraemia in BEFV-infected cattle. Plasma from four virus-infected and uninfected negative control animals was tested by cytokine-specific immunoenzymatic assays, viraemia monitored by qRT-PCR, and virus neutralizing antibody titres determined using a standard protocol. Unlike the negative controls, plasma IL-6 and IL-10 were increased in all the virus-infected animals starting several days prior to initiation of viraemia. In one animal, plasma IL-2 and IFN-γ were consistently higher than in the other three virus-infected animals and the negative control mean. The animal with the strongest IL-2 and IFN-γ responses had the shortest viraemia while the heifer with the lowest IL-2/IFN-γ indices demonstrated the longest viraemia. Evidently, increase in plasma IL-6 and IL-10 precedes seroconversion during BEFV infections in cattle suggesting the two cytokines may influence immunological events that pave way to B-cell activation and seroconversion. While there is remarkable variability in IL-2 and IFN-γ expression amongst BEFV-infected animals, increased plasma levels of the two cytokines appear to be associated with a shorter viraemia. Ongoing studies will help define the precise role of T cells in anti-BEFV adaptive immune responses.

The Norwich Patellar Instability Score: Validity, internal consistency and responsiveness for people conservatively-managed following first-time patellar dislocation.

BACKGROUND: This paper assessed the validity, internal consistency, responsiveness and floor-ceiling effects of the Norwich Patellar Instability (NPI) Score for a cohort of conservatively managed people following first-time patellar dislocation (FTPD). METHODS: Fifty patients were recruited, providing 130 completed datasets over 12 months. The NPI Score, Lysholm Knee Score, Tegner Level of Activity Score and isometric knee extension strength were assessed at baseline, six weeks, six and 12 months post-injury. RESULTS: There was high convergent validity with a statistically significant correlation between the NPI Score and the Lysholm Knee Score (p<0.001), Tegner Level of Activity Score (p<0.001) and isometric knee extension strength (p<0.002). Principal component analysis revealed that the NPI Score demonstrated good concurrent validity with four components account for 70.4% of the variability. Whilst the NPI Score demonstrated a flooring-effect for 13 of the 19 items, no ceiling effect was reported. There was high internal consistency with a Cronbach Alpha value of 0.93 (95% CI: 0.91 to 0.93). The NPI Score was responsive to change over the 12 months period with an effect size of 1.04 from baseline to 12 months post-injury. CONCLUSIONS: The NPI Score is a valid tool to assess patellar instability symptoms in people conservatively managed following FTPD. LEVEL OF EVIDENCE: Level II.

Died of wounds: a mortality review.

OBJECTIVES: Combat casualty care is a complex system involving multiple clinicians, medical interventions and casualty transfers. Improving the performance of this system requires examination of potential weaknesses. This study reviewed the cause and timing of death of casualties deemed to have died from their injuries after arriving at a medical treatment facility during the recent conflicts in Iraq and Afghanistan, in order to identify potential areas for improving outcomes. METHODS: This was a retrospective review of all casualties who reached medical treatment facilities alive, but subsequently died from injuries sustained during combat operations in Afghanistan and Iraq. It included all deaths from start to completion of combat operations. The UK military joint theatre trauma registry was used to identify cases, and further data were collected from clinical notes, postmortem records and coroner's reports. RESULTS: There were 71 combat-related fatalities who survived to a medical treatment facility; 17 (24%) in Iraq and 54 (76%) in Afghanistan. Thirty eight (54%) died within the first 24 h. Thirty-three (47%) casualties died from isolated head injuries, a further 13 (18%) had unsurvivable head injuries but not in isolation. Haemorrhage following severe lower limb trauma, often in conjunction with abdominal and pelvic injuries, was the cause of a further 15 (21%) deaths. CONCLUSIONS: Severe head injury was the most common cause of death. Irrespective of available medical treatment, none of this group had salvageable injuries. Future emphasis should be placed in preventative strategies to protect the head against battlefield trauma.

Kinetics of pro-inflammatory cytokines, interleukin-10, and virus neutralising antibodies during acute ephemeral fever virus infections in Brahman cattle.

While fever and inflammation are hallmark features of bovine ephemeral fever (BEF), the cytokine networks that underlie the acute phase of the disease have not been empirically defined in cattle. This study characterised the plasma kinetics of proinflammatory cytokines (IL-1ß, IL-6, TNF-α) and IL-10 during acute BEF and elucidated on the relationship between the onset of the virus neutralizing antibody response and resolution of viraemia in natural BEF virus (BEFV) infections in cattle. Plasma from three BEFV-infected and three uninfected cattle was tested for the study cytokines by a cELISA, viraemia monitored by qRT-PCR, and virus neutralizing antibody titres determined using a standard protocol. Unlike the negative controls, plasma concentrations of IL-1ß, TNF-α, IL-6, and IL-10 were consistently increased in the three virus-infected animals. Two of the infected heifers were recumbent and pyrexic on the first day of monitoring and increased cytokine production was already in progress by the time viraemia was detected in all the three infected animals. In all the virus-infected heifers, IL-1ß was the most strongly expressed cytokine, IL-6 and IL-10 manifested intermediate plasma concentrations while TNF-α was the least expressed and demonstrated bi-phasic peaks three and five days after the onset of pyrexia. In two of the BEFV-infected heifers, viraemia resolved on the day of seroconversion while in the other infected animal, viral RNA was detectable up to three days after seroconversion. The present data document variable increase in plasma IL-1ß, IL-6, TNF-α, and IL-10 during natural BEFV infections and the fact that upregulation of all but TNF-α precedes seroconversion. In addition to virus neutralising antibodies, it is likely that cytokine-mediated cellular mechanisms may be required for resolution of viraemia in BEF. Considering the anti-inflammatory properties of IL-10, its upregulation may potentially antagonise the fever response in BEFV-infected cattle.

Rehabilitation following first-time patellar dislocation: a randomised controlled trial of purported vastus medialis obliquus muscle versus general quadriceps strengthening exercises.

BACKGROUND: We aimed to define whether distal vastus medialis (VM) muscle strengthening improves functional outcomes compared to general quadriceps muscle strengthening following first-time patellar dislocation (FTPD). METHODS: Fifty patients post-FTPD were randomised to either a general quadriceps exercise or rehabilitation programme (n=25) or a specific-VM exercise and rehabilitation regime (n=25). The primary outcome was the Lysholm knee score, and secondary outcomes included the Tegner Level of Activity score, the Norwich Patellar Instability (NPI) score, and isometric knee extension strength at various knee flexion ranges of motion. Outcomes were assessed at baseline, six weeks, six months and 12months. RESULTS: There were statistically significant differences in functional outcome and activity levels with the Lysholm knee score and Tegner Level of Activity score at 12months in the general quadriceps exercise group compared to the VM group (p=0.05; 95% confidence interval (CI): -14.0 to 0.0/p=0.04; 95% CI: -3.0 to 0.0). This did not reach a clinically important difference. There was no statistically significant difference between the groups for the NPI score and isometric strength at any follow-up interval. The trial experienced substantial participant attrition (52% at 12months). CONCLUSIONS: Whilst there was a statistical difference in the Lysholm knee score and Tegner Level of Activity score between general quadriceps and VM exercise groups at 12months, this may not have necessarily been clinically important. This trial highlights that participant recruitment and retention are challenges which should be considered when designing future trials in this population. LEVEL OF EVIDENCE: Therapeutic study, Level I.

No statistically significant kinematic difference found between a cruciate-retaining and posterior-stabilised Triathlon knee arthroplasty: a laboratory study involving eight cadavers examining soft-tissue laxity.

The aim of this study was to compare the maximum laxity conferred by the cruciate-retaining (CR) and posterior-stabilised (PS) Triathlon single-radius total knee arthroplasty (TKA) for anterior drawer, varus-valgus opening and rotation in eight cadaver knees through a defined arc of flexion (0º to 110º). The null hypothesis was that the limits of laxity of CR- and PS-TKAs are not significantly different. The investigation was undertaken in eight loaded cadaver knees undergoing subjective stress testing using a measurement rig. Firstly the native knee was tested prior to preparation for CR-TKA and subsequently for PS-TKA implantation. Surgical navigation was used to track maximal displacements/rotations at 0º, 30º, 60º, 90º and 110° of flexion. Mixed-effects modelling was used to define the behaviour of the TKAs. The laxity measured for the CR- and PS-TKAs revealed no statistically significant differences over the studied flexion arc for the two versions of TKA. Compared with the native knee both TKAs exhibited slightly increased anterior drawer and decreased varus-valgus and internal-external roational laxities. We believe further study is required to define the clinical states for which the additional constraint offered by a PS-TKA implant may be beneficial.