Perioperative administration of tranexamic acid in hip fracture surgery (The PATHS study): national audit of current practice.

INTRODUCTION: Neck of femur fractures (NOFF) are associated with significant morbidity and mortality, exacerbated by anaemia. Evidence indicates tranexamic acid (TXA) administration in NOFF surgery reduces blood loss and transfusion requirements, without increasing complications. The aim of this study was to establish current TXA administration practice in patients undergoing surgery for NOFF in the UK. METHODS: We conducted a multicentre prospective study within the UK over a two-week period in March 2019. Pre-, intra- and postoperative data were collected locally and analysed centrally. RESULTS: Data for 917 patients were submitted from 66 institutions. Of those eligible, 48.0% received TXA perioperatively. Administration rates varied from 0 to 100%. Significantly greater numbers undergoing arthroplasty received TXA (57.6%) compared with internal fixation (38.4%, p<0.01). Some 15.2% of institutions had a protocol for TXA use in NOFF. Patients treated in these units were significantly more likely to receive TXA (86.7%) than those who were not (41.2% p<0.01). Of those receiving TXA, 92.3% were given 1g intravenously (IV) at anaesthetic administration. CONCLUSIONS: Despite supportive evidence for its use, a wide variation in the administration of TXA between hospitals and procedures has been demonstrated. Administration rates were higher for arthroplasty than for fixation procedures. Most centres do not have a protocol guiding TXA administration. We recommend administration of 1g IV TXA perioperatively for patients undergoing NOFF surgery, where not contraindicated, unless future randomised controlled trials support an alternative regimen. We recommend units include their own locally agreed TXA policy within a written protocol for the care of NOFF patients.

Macroinfauna responses and recovery trajectories after an oil spill differ from those following saltmarsh restoration.

Given the severity of injuries to biota in coastal wetlands from the Deepwater Horizon oil spill (DWH) and the resulting availability of funding for restoration, information on impacted salt marshes and biotic development of restored marshes may both help inform marsh restoration planning in the near term and for future spills. Accordingly, we performed a meta-analysis to model a restoration trajectory of total macroinfauna density in constructed marshes (studied for ~30 y), and with a previously published restoration trajectory for amphipods, we compared these to recovery curves for total macroinfauna and amphipods from DWH impacted marshes (over 8.5 y). Total macroinfauna and amphipod densities in constructed marshes did not consistently reach equivalency with reference sites before 20 y, yet in heavily oiled marshes recovery occurred by 4.5 y post spill (although it is unlikely that macroinfaunal community composition fully recovered). These differences were probably due to initial conditions (e.g., higher initial levels of belowground organic matter in oiled marshes) that were more conducive to recovery as compared to constructed marshes. Furthermore, we found that amphipod trajectories were distinctly different in constructed and oiled marshes as densities at oiled sites exceeded that of reference sites by as much as 20x during much of the recovery period. Amphipods may have responded to the rapid increase and high biomass of benthic microalgae following the spill. These results indicate that biotic responses after an oil spill may be quantitatively different than those following restoration, even for heavily oiled marshes that were initially denuded of vegetation. Our dual trajectories for oil spill recovery and restoration development for macroinfauna should help guide restoration planning and assessment following the DWH as well as for restoration scaling for future spills.

Is the number of new trauma and orthopaedic consultant posts increasing or decreasing?

Introduction Trauma and orthopaedics is a popular surgical specialty in the UK. Recent changes to the National Health Service have suggested an imbalance with fewer jobs yet more trainees. Furthermore, subspecialisation is emerging within all surgical disciplines. The aim of this study was to examine whether there were decreasing numbers of trauma and orthopaedic (T&O) consultant appointments in the UK, and to determine the frequency of subspecialisation. Methods All 51 issues of the British Medical Journal (BMJ) careers supplement from the year 2000 were reviewed as well as the 51 issues from 2010. The number of T&O posts, requested subspecialty interests and the number of posts in other surgical specialties were analysed. Results A total of 481 consultant posts in T&O were advertised in the 102 issues of the careers supplements reviewed. Of these, 281 were advertised in 2000 and 200 in 2010. The mean number of posts per issue was 5.5 in 2000 and 3.9 in 2010. In 2000 orthopaedic posts represented 30.5% of all surgical posts while in 2010 this was 37.8%. Under two-thirds (61.6%) of posts requested a specialty interest in 2000 but this increased to 93% in 2010. The greatest increase in named subspecialty was seen in 'spine' (from 4.1% to 19.0%.) while 'general' had the greatest decrease (from 38.4% to 7.0%). Conclusions UK consultant posts in T&O are decreasing in frequency. Most advertised posts request a subspecialty interest but registrar training focuses on producing 'generally' competent orthopaedic consultants. The onus is therefore on fellowships to develop subspecialty interest. As these are not all educationally approved, reconfiguration of fellowships is likely to be necessary.

Chitayat syndrome: hyperphalangism, characteristic facies, hallux valgus and bronchomalacia results from a recurrent c.266A>G p.(Tyr89Cys) variant in the ERF gene.

BACKGROUND: In 1993, Chitayat et al., reported a newborn with hyperphalangism, facial anomalies, and bronchomalacia. We identified three additional families with similar findings. Features include bilateral accessory phalanx resulting in shortened index fingers; hallux valgus; distinctive face; respiratory compromise. OBJECTIVES: To identify the genetic aetiology of Chitayat syndrome and identify a unifying cause for this specific form of hyperphalangism. METHODS: Through ongoing collaboration, we had collected patients with strikingly-similar phenotype. Trio-based exome sequencing was first performed in Patient 2 through Deciphering Developmental Disorders study. Proband-only exome sequencing had previously been independently performed in Patient 4. Following identification of a candidate gene variant in Patient 2, the same variant was subsequently confirmed from exome data in Patient 4. Sanger sequencing was used to validate this variant in Patients 1, 3; confirm paternal inheritance in Patient 5. RESULTS: A recurrent, novel variant NM_006494.2:c.266A>G p.(Tyr89Cys) in ERF was identified in five affected individuals: de novo (patient 1, 2 and 3) and inherited from an affected father (patient 4 and 5). p.Tyr89Cys is an aromatic polar neutral to polar neutral amino acid substitution, at a highly conserved position and lies within the functionally important ETS-domain of the protein. The recurrent ERF c.266A>C p.(Tyr89Cys) variant causes Chitayat syndrome. DISCUSSION: ERF variants have previously been associated with complex craniosynostosis. In contrast, none of the patients with the c.266A>G p.(Tyr89Cys) variant have craniosynostosis. CONCLUSIONS: We report the molecular aetiology of Chitayat syndrome and discuss potential mechanisms for this distinctive phenotype associated with the p.Tyr89Cys substitution in ERF.

Development of bingeing in rats altered by a small operant requirement.

Previous studies have shown that providing an optional food for a brief period of time to non-food deprived rats on an intermittent basis in the home cage engenders significantly more intake (binge-type behavior) than when the optional food is provided for a brief period on a daily basis. Experiment 1 examined the effects of placing a small operant response requirement on access to an optional food (vegetable shortening) on the establishment of binge-type behavior. Experiment 2 examined the effects of different schedules of reinforcement, a period of abstinence from shortening, and 24h of food deprivation on established binge-type behavior. In Experiment 1 the group of rats with 30-min access to shortening on an intermittent basis in their home cages (IC) consumed significantly more shortening than the group with 30-min daily access in the home cage (DC). The group with 30-min intermittent access in an operant chamber (IO group) earned significantly more reinforcers than the group with 30-min daily access in an operant chamber (DO). In Experiment 2, the IO group earned significantly more reinforcers than the DO group regardless of the response cost, the period of shortening abstinence, and overnight food deprivation. These results demonstrate that while intermittent access generates binge-type eating, the size of the binge (intake) can be altered by different contingency arrangements.

Stable Isotope Models Predict Foraging Habitat of Northern Fur Seals (Callorhinus ursinus) in Alaska.

We developed models to predict foraging habitat of adult female northern fur seals (Callorhinus ursinus) using stable carbon (δ13C) and nitrogen (δ15N) isotope values from plasma and red blood cells. Binomial generalized linear mixed models were developed using blood isotope samples collected from 35 adult female fur seals on three breeding colonies in Alaska during July-October 2006. Satellite location and dive data were used to define habitat use in terms of the proportion of time spent or dives made in different oceanographic/bathymetric domains. For both plasma and red blood cells, the models accurately predicted habitat use for animals that foraged exclusively off or on the continental shelf. The models did not perform as well in predicting habitat use for animals that foraged in both on- and off-shelf habitat; however, sample sizes for these animals were small. Concurrently collected scat, fatty acid, and dive data confirmed that the foraging differences predicted by isotopes were associated with diet differences. Stable isotope samples, dive data, and GPS location data collected from an additional 15 females during August-October 2008 validated the effective use of the models across years. Little within year variation in habitat use was indicated from the comparison between stable isotope values from plasma (representing 1-2 weeks) and red blood cells (representing the prior few months). Constructing predictive models using stable isotopes provides an effective means to assess habitat use at the population level, is inexpensive, and can be applied to other marine predators.

Packaging modifications for protecting flavor of extended-shelf-life milk from light.

The effectiveness of titanium dioxide (TiO2)-loaded high-density polyethylene (HDPE) to reduce light-induced oxidation of extended-shelf-life milk (2% total fat) was studied. The objective was to determine differences over time in sensory quality, vitamin retention, and oxidative chemistry as a function of packaging and retail light exposure duration. Effectiveness of packaging for protecting milk quality was assessed by sensory evaluation (triangle tests, untrained panel), changes in volatile compounds, thiobarbituric reactive substances (TBARS), and riboflavin concentration. Milk (2%) was stored in HDPE packages consisting of TiO2 at 3 levels (low: 0.6%; medium: 1.3%; high: 4.3%) at 3 °C for up to 43 d. Light-protected (translucent, foil-wrapped) and light-exposed (translucent) HDPE packages served as controls. The high TiO2-HDPE package provided protection similar to light-protected control package through d 22 of light exposure, with less consistent performance by the medium TiO2 package. The TBARS increased in all treatments during storage. Under the experimental conditions used, a TBARS value of 1.3mg/L could be considered the limiting sensory threshold for differentiating oxidized milk from light-protected milk. Riboflavin concentration decreased 10.5% in the light-protected control and 28.5% in the high TiO2 packaged milk past 29 d of light exposure, but losses were greater than 40% for all other packages. The high TiO2 package protected riboflavin concentration from degradation and controlled aldehyde concentration throughout the test period.

Comprehensive analysis of karyotypic mosaicism between trophectoderm and inner cell mass.

Aneuploidy has been well-documented in blastocyst embryos, but prior studies have been limited in scale and/or lack mechanistic data. We previously reported preclinical validation of microarray 24-chromosome preimplantation genetic screening in a 24-h protocol. The method diagnoses chromosome copy number, structural chromosome aberrations, parental source of aneuploidy and distinguishes certain meiotic from mitotic errors. In this study, our objective was to examine aneuploidy in human blastocysts and determine correspondence of karyotypes between trophectoderm (TE) and inner cell mass (ICM). We disaggregated 51 blastocysts from 17 couples into ICM and one or two TE fractions. The average maternal age was 31. Next, we ran 24-chromosome microarray molecular karyotyping on all of the samples, and then performed a retrospective analysis of the data. The average per-chromosome confidence was 99.95%. Approximately 80% of blastocysts were euploid. The majority of aneuploid embryos were simple aneuploid, i.e. one or two whole-chromosome imbalances. Structural chromosome aberrations, which are common in cleavage stage embryos, occurred in only three blastocysts (5.8%). All TE biopsies derived from the same embryos were concordant. Forty-nine of 51 (96.1%) ICM samples were concordant with TE biopsies derived from the same embryos. Discordance between TE and ICM occurred only in the two embryos with structural chromosome aberration. We conclude that TE karyotype is an excellent predictor of ICM karyotype. Discordance between TE and ICM occurred only in embryos with structural chromosome aberrations.

The effect of trainee involvement on procedure and list times: A statistical analysis with discussion of current issues affecting orthopaedic training in UK.

INTRODUCTION: Training surgeons adds time to the duration of procedures and operation lists. This is not accounted for in the finance received to perform the operation by the hospital in the Payment by Results (PbR) system. PURPOSE OF THE STUDY: To find out: 1. The effect on the duration of a procedure and the number of procedures performed on the list when a trainee is involved. 2. The percentage of orthopaedic cases with trainee involvement. 3. The effect of European working time directive (EWTD) on the trainee involvement in cases from theatre data in 2008 versus logbook data from 2004 - 2008. METHODS: Data was taken from two different sources. Firstly, the Operating Room Information System (ORMIS) and patient operation notes. The second source was a consultant's logbook comprising 227 primary total knee replacements performed between 2004 and 2008. RESULTS: The data produced trends suggesting trainees took longer to perform procedures than consultants. In orthopaedic operations, 92% of cases had trainees present and of these 17% of cases were performed by trainees in 2008. Before the implementation of the EWTD, trainees performed more procedures when compared with current logbook data (38% versus 17% cases). Time taken by a trainee to perform the procedure under direct consultant supervision was significantly higher in comparison to procedures performed by a consultant alone (P = < 0.0001). Analysing the ORMIS and logbook data gave similar conclusions. DISCUSSION & CONCLUSION: Hospitals should be given financial recognition for training. In this debate, we should remain focused on the provision of quality training for the next generation of surgeons.

Preclinical validation of a microarray method for full molecular karyotyping of blastomeres in a 24-h protocol.

BACKGROUND: Preimplantation genetic screening (PGS) has been used in an attempt to determine embryonic aneuploidy. Techniques that use new molecular methods to determine the karyotype of an embryo are expanding the scope of PGS. METHODS: We introduce a new method for PGS, termed 'parental support', which leverages microarray measurements from parental DNA to 'clean' single-cell microarray measurements on embryonic cells and explicitly computes confidence in each copy number call. The method distinguishes mitotic and meiotic copy errors and determines parental source of aneuploidy. RESULTS: Validation with 459 single cells of known karyotype indicated that per-cell false-positive and false-negative rates are roughly equivalent to the 'gold standard' metaphase karyotype. The majority of the cells were run in parallel with a clinical commercial PGS service. Computed confidences were conservative and roughly concordant with accuracy. To examine ploidy in human embryos, the method was then applied to 26 disaggregated, cryopreserved, cleavage-stage embryos for a total of 134 single blastomeres. Only 23.1% of the embryos were euploid, though 46.2% of embryos were mosaic euploid. Mosaicism affected 57.7% of the embryos. Counts of mitotic and meiotic errors were roughly equivalent. Maternal meiotic trisomy predominated over paternal trisomy, and maternal meiotic trisomies were negatively predictive of mosaic euploid embryos. CONCLUSIONS: We have performed a major preclinical validation of a new method for PGS and found that the technology performs approximately as well as a metaphase karyotype. We also directly measured the mechanism of aneuploidy in cleavage-stage human embryos and found high rates and distinct patterns of mitotic and meiotic aneuploidy.

Arthroscopic anterior cruciate ligament surgery: results of autogenous patellar tendon graft versus the Leeds-Keio synthetic graft five year follow-up of a prospective randomised controlled trial.

We conducted a prospective, randomised controlled trial comparing anterior cruciate ligament reconstruction using middle third patellar tendon graft (PT) to synthetic Leeds-Keio (LK) ligament. The patients were randomised (26 PT, 24 LK). Subjective knee function was classified (Lysholm, Tegner activity, IKDC scores), laxity was measured (Lachman test, Stryker laxometer), and functional ability was assessed (one-hop test). There were no significant differences between Lysholm or IKDC scores at any stage by 5 years. Significant differences were found between the groups at 2 years for Tegner activity scores, laxity and one-hop testing. By 5 years there were no significant differences. Clinical equivalence was demonstrated between the two groups for the Lysholm score and one-hop test but not for the Tegner activity score at 5 years. The use of the LK ligament has been largely abandoned due to reports of its insufficiency. Our results demonstrate that it is not as inferior as one might expect. We conclude that the results of LK ligament ACL reconstruction are as acceptable as those using PT. It may provide an additional means of reconstruction where no suitable alternative is present.

Access conditions affect binge-type shortening consumption in rats.

When non-food-deprived rats are given intermittent access to certain substances, consumption of those substances is greater than when more frequent access is provided. The present study examined the effects of three different shortening access conditions on subsequent shortening intake in rats. Each of the three different shortening conditions lasted five weeks and was followed by a five-week period in which shortening access was limited by time (1 h of availability) on either an Intermittent (Monday, Wednesday, Friday) or Daily schedule of access. In Part 1, limiting the quantity of shortening provided during the 1-h period of availability attenuated subsequent 1-h shortening intake in the Intermittent access group, but had no statistically significant effect in the Daily access group. In Part 2, unrestricted availability of shortening (24 h/day-7 days/week) attenuated subsequent 1-h shortening intake in all groups. In Part 3, shortening non-availability for five weeks enhanced subsequent 1-h shortening intake in all groups. It was also shown that rats under an Intermittent, but not a Daily, schedule of access consumed as much shortening during a 1-h period of availability, as was consumed in 24 h when shortening availability was unrestricted. These results demonstrate that while intermittent access is necessary and sufficient to stimulate binge-type eating in rats, the behavioral history can modulate binge size.

How accurate are lockable orthotic knee braces? An objective gait analysis study.

There has been an increasing use of orthotic knee braces in the management of knee injuries but, to our knowledge, there is no gait analysis study assessing the accuracy of these braces. Eight healthy male subjects were studied to determine the accuracy of immobilisation or splintage provided by a lockable orthotic knee brace using gait analysis. Six types of immobilisation were studied: locked at 0, 10, 20, 30 degrees and unlocked in an orthotic knee brace, and without a brace. The knee flexion angles measured using the kinematic instruments at 0 and 10 degrees were significantly greater than those set at the knee brace. The knee flexion angle measured using the unlocked knee brace was significantly greater than that measured in the absence of a brace. This study highlights inaccuracies in a knee brace at low knee flexion angles. The higher actual angles alter the biomechanics of the knee joint and result in greater forces across the knee joint and especially the extensor mechanism.

The relationship of the angle of immobilisation of the knee to the force applied to the extensor mechanism when partially weight-bearing. A gait-analysis study in normal volunteers.

We describe the influence of the angle of immobilisation during partial weight-bearing on the forces across the extensor mechanism of the knee. Gait analysis was performed on eight healthy male subjects with the right knee in an orthotic brace locked at 0 degree, 10 degrees, 20 degrees and 30 degrees, with the brace unlocked and also without a brace. The ground reaction force, the angle of the knee and the net external flexion movement about the knee were measured and the extensor mechanism force was calculated. The results showed a direct non-linear relationship between the angle of knee flexion and the extensor mechanism force. When a brace was applied, the lowest forces occurred when the brace was locked at 0 degree. At 30 degrees the forces approached the failure strength of some fixation devices. We recommend that for potentially unstable injuries of the extensor mechanism, when mobilising with partial weight-bearing, the knee should be flexed at no more than 10 degrees.

The role of preoperative templating in total knee arthroplasty: comparison of three prostheses.

Templating of preoperative radiographs is routinely recommended prior to knee arthroplasty. We performed this study to assess the reproducibility and accuracy of the templates for three commonly used knee implants (PFC, Kinemax, Scorpio). Six lower limb surgeons templated 10 patients for each of the three designs. The inter- and intra-observer reliability and accuracy was calculated. There was marked variation in the reliability of the templating with the tibial insert scoring better than the femoral and the Kinemax being the most reproducible of the three. In general, the intra-observer scores (kappa=0.57-0.81) were better than the inter-observer ones (kappa=0.21-0.60). The Scorpio was the most accurately templated of the three implants, with the percentage correlating with what was actually implanted ranging from 55% to 62% for the femur and 72% to 75% for the tibia, with no templated sizes more than one size different from the actual implant. The other implants ranged from 38% to 42% for the femur and 53% to 58% for the tibia with both having up to 3% more than 1 size difference from the actual implant. We believe that the use of templating in total knee arthroplasty should be interpreted with caution and we urge the development of more accurate prosthesis sizing techniques.

Re-admission rates within 28 days of total hip replacement.

INTRODUCTION: The aim of the study was to identify the reasons for the higher than expected emergency re-admission to hospital within 28 days of total hip replacement (THR) for Stepping Hill Hospital, Stockport. PATIENTS AND METHODS: Over a 42-month period, 65 (8.5%) of 769 patients were re-admitted within 28 days of discharge following primary THR. Case notes for 61 patients were available for retrospective review to assess premorbidity, initial postoperative complications and reason for re-admission. RESULTS: The main reasons for re-admission were complications related to the procedure. These included thrombo-embolic disease 2.5%, atraumatic dislocation 1.4%, wound complications 1.2% and swollen limb 1.8%. Other causes such as admission to another department for problems not related to THR accounted for 0.8%. CONCLUSIONS: Our findings are comparable with the published literature for early complications following THR. The three main reasons for re-admission were atraumatic dislocation, thrombo-embolic and wound complications such as superficial infection and haematoma are the commonest world-wide. The re-admission rate to hospital within the first 28 days following THR was a clinical indicator suggested by the UK Department of Health. It has subsequently been incorporated in a group of indicators used by the CASPE Healthcare Knowledge Systems (CHKS), a private healthcare consultancy and analysis company, for peer benchmarking. Our re-admission rates are inflated by admissions for non-THR-related reasons. The level of post-THR complications leading to re-admission were acceptable compared with the available published literature regarding 28-day re-admission. We anticipate that this study may act as a benchmark for other trusts.