Pre-operative resuscitation discussion with patients undergoing fractured neck of femur repair: a service evaluation and discussion of current standards.

INTRODUCTION: The majority of neck of femur (NOF) fracture patients are frail and at a higher risk of cardiac arrest. This makes discussion of treatment escalation vital to informed care. The optimal time for these discussions is prior to admission or trauma. However, when this has not occurred, it is vital that these discussions happen early in the patient's admission when family is often present and before further deterioration in their condition. We undertook a service evaluation to evaluate and discuss the effect of clinician education on improving rates of timely discussion amongst orthopaedic doctors. MATERIALS AND METHODS: The first cycle included 94 patients. Their notes were reviewed for presence of a ReSPECT (Recommend Summary Plan for Emergency Care and Treatment) form prior to operation and whether this it countersigned by a consultant. Following this, clinician education was undertaken and a re-audit was carried out involving 57 patients. RESULTS: ReSPECT form completion rates rose from 23% in cycle 1-32% in cycle 2 following intervention. The proportion which consultants signed rose from 41% to 56% following intervention. CONCLUSION: This project demonstrates how a basic education program can prove limited improvements in the rates of timely resuscitation discussions. We discuss a current lack in quality research into educational programs for discussion of treatment escalation for orthopaedic trainees. We suggest there is room to improve national best practice guidelines and training to ensure these discussions are carried out more frequently and to a better standard.

The safety and efficacy of day-case total joint arthroplasty.

INTRODUCTION: The popularity of day-case arthroplasty has been fuelled by focus on its cost effectiveness for the healthcare system. Safety concerns still remain. The aim of this review was to compare readmission rates after total joint arthroplasty for patients undergoing day-case surgery and for inpatients. METHODS: A comprehensive online search of databases was performed for all published articles in the English language evaluating readmission rates after total hip arthroplasty (THA) and total knee arthroplasty (TKA). Seventeen studies were deemed eligible and included in the meta-analysis. RESULTS: All studies included in the meta-analysis described readmission rates following THA/TKA. The readmission rate for day-case patients was 1.9% (n=124) whereas for inpatients, it was 2.0% (n=12,399). Compared with inpatient arthroplasty, day-case arthroplasty was associated with lower total readmission rates (odds ratio [OR]: 0.77, 95% confidence interval [CI]: 0.63-0.94, p=0.01). Furthermore, day-case surgery conferred a decrease in readmission rates for both THA (1.3% vs 7.0%) and TKA (2.7% vs 4.3%). Moreover, day-case THA and TKA were both associated with a decreased chance of readmission (OR: 0.27, 95% CI: 0.17-0.42, p<0.00001; and OR: 0.55, 95% CI: 0.42-0.72, p<0.00001 respectively). CONCLUSIONS: This review emphasises that with a thoughtful, designated protocol and with careful patient selection, day-case arthroplasty is a safe and effective option.

The accuracy of pre-operative (P)-POSSUM scoring and cardiopulmonary exercise testing in predicting morbidity and mortality after pancreatic and liver surgery: A systematic review.

BACKGROUND: Cardiopulmonary exercise-testing (CPET) and the (Portsmouth) Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity ((P)-POSSUM) are used as pre-operative risk stratification and audit tools in general surgery, however, both have been demonstrated to have limitations in major hepatopancreatobiliary (HPB) surgery. MATERIALS AND METHODS: The aim of this review is to determine if CPET and (P)-POSSUM scoring systems accurately predict morbidity and mortality. Eligible articles were identified with an electronic database search. Analysis according to surgery type and tool used was performed. RESULTS: Twenty-five studies were included in the final review. POSSUM predicted morbidity demonstrated weighted O/E ratios of 0.75(95%CI0.57-0.97) in hepatic surgery and 0.85(95%CI0.8-0.9) in pancreatic surgery. P-POSSUM predicted mortality in pancreatic surgery demonstrated an O/E ratio of 0.75(95%CI0.27-2.13) and 0.94(95%CI0.57-1.55) in hepatic surgery. In both pancreatic and hepatic surgery an anaerobic threshold(AT) of between 9 0.5-11.5 ml/kg/min was predictive of post-operative complications, and in pancreatic surgery ventilatory equivalence of carbon dioxide(˙VE/˙VCO2) was predictive of 30-day mortality. CONCLUSION: POSSUM demonstrates an overall lack of predictive fit for morbidity, whilst CPET variables provide some predictive power for post-operative outcomes. Development of a new HPB specific risk prediction tool would be beneficial; the combination of parameters from POSSUM and CPET, alongside HPB specific markers could overcome current limitations.

Antibodies from Sierra Leonean and Nigerian Lassa fever survivors cross-react with recombinant proteins representing Lassa viruses of divergent lineages.

Lassa virus (LASV) is the causative agent of Lassa fever, an often-fatal hemorrhagic disease that is endemic in West Africa. Seven genetically distinct LASV lineages have been identified. As part of CEPI's (Coalition for Epidemic Preparedness Innovations) Lassa vaccine development program, we assessed the potential of the human immune system to mount cross-reactive and cross-protective humoral immune responses to antigens from the most prevalent LASV lineages, which are lineages II and III in Nigeria and lineage IV in Sierra Leone. IgG and IgM present in the blood of Lassa fever survivors from Nigeria or Sierra Leone exhibited substantial cross-reactivity for binding to LASV nucleoprotein and two engineered (linked and prefusion) versions of the glycoproteins (GP) of lineages II-IV. There was less cross-reactivity for the Zinc protein. Serum or plasma from Nigerian Lassa fever survivors neutralized LASV pseudoviruses expressing lineage II GP better than they neutralized lineage III or IV GP expressing pseudoviruses. Sierra Leonean survivors did not exhibit a lineage bias. Neutralization titres determined using LASV pseudovirus assays showed significant correlation with titres determined by plaque reduction with infectious LASV. These studies provide guidance for comparison of humoral immunity to LASV of distinct lineages following natural infection or immunization.

Effect of breed as a risk factor for humeral condylar fracture in skeletally immature dogs.

OBJECTIVES: To investigate the effect of breed as a risk factor associated with humeral condylar fracture in skeletally immature dogs in the UK. MATERIALS AND METHODS: Retrospective study of dogs under 12 months of age that were presented with humeral condylar fracture to three specialist referral centres between 2015 and 2018. Data retrieved from medical records included breed, age, gender, neuter status, affected limb, fracture configuration and aetiology of the fracture. Breed population percentages were compared with those recorded by the UK Kennel Club. RESULTS: Of the 115 dogs with 118 fractures, French bulldogs (41%) and English springer spaniels (15%) were overrepresented: humeral condylar fractures were more commonly diagnosed in French bulldogs (odds ratio = 5.86) and English springer spaniels (odds ratio = 5.66) compared with mixed-breed dogs. Lateral condylar fractures occurred in 70% of cases, with medial condylar fractures and Y/T fractures accounting for 9% and 21%, respectively. Median age at the time of fracture was 4 months (range 2 to 10 months). CLINICAL SIGNIFICANCE: French bulldogs and English springer spaniels were identified as being at potentially increased risk of humeral condylar fracture in skeletally immature dogs.

Preoperative systemic inflammation and perioperative myocardial injury: prospective observational multicentre cohort study of patients undergoing non-cardiac surgery.

BACKGROUND: Systemic inflammation is pivotal in the pathogenesis of cardiovascular disease. As inflammation can directly cause cardiomyocyte injury, we hypothesised that established systemic inflammation, as reflected by elevated preoperative neutrophil-lymphocyte ratio (NLR) >4, predisposes patients to perioperative myocardial injury. METHODS: We prospectively recruited 1652 patients aged ≥45 yr who underwent non-cardiac surgery in two UK centres. Serum high sensitivity troponin T (hsTnT) concentrations were measured on the first three postoperative days. Clinicians and investigators were blinded to the troponin results. The primary outcome was perioperative myocardial injury, defined as hsTnT≥14 ng L-1 within 3 days after surgery. We assessed whether myocardial injury was associated with preoperative NLR>4, activated reactive oxygen species (ROS) generation in circulating monocytes, or both. Multivariable logistic regression analysis explored associations between age, sex, NLR, Revised Cardiac Risk Index, individual leukocyte subsets, and myocardial injury. Flow cytometric quantification of ROS was done in 21 patients. Data are presented as n (%) or odds ratio (OR) with 95% confidence intervals. RESULTS: Preoperative NLR>4 was present in 239/1652 (14.5%) patients. Myocardial injury occurred in 405/1652 (24.5%) patients and was more common in patients with preoperative NLR>4 [OR: 2.56 (1.92-3.41); P<0.0001]. Myocardial injury was independently associated with lower absolute preoperative lymphocyte count [OR 1.80 (1.50-2.17); P<0.0001] and higher absolute preoperative monocyte count [OR 1.93 (1.12-3.30); P=0.017]. Monocyte ROS generation correlated with NLR (r=0.47; P=0.03). CONCLUSIONS: Preoperative NLR>4 is associated with perioperative myocardial injury, independent of conventional risk factors. Systemic inflammation may contribute to the development of perioperative myocardial injury. CLINICAL TRIAL REGISTRATION: NCT01842568.

Laparoscopic Ovarian Transposition and Ovariopexy for Fertility Preservation in Patients Treated with Pelvic Radiotherapy with or without Chemotherapy.

BACKGROUND: Preservation of fertility in cancer patients of reproductive age is a concern for both the patient and the clinician. In this study, we aimed to study the effectiveness of laparoscopic ovarian transposition or ovariopexy in preserving ovarian function in women undergoing pelvic radiotherapy with or without chemotherapy for pelvic tumours. METHODS: The records of patients who underwent laparoscopic ovarian transposition or ovariopexy prior to pelvic radiation therapy between 2002 and 2018 were reviewed retrospectively. RESULTS: Thirty-nine women or adolescent girls with a diagnosis of cervical cancer (n=15), Hodgkin's lymphoma (n=6) or other types of pelvic tumours (n=18) were included in the study. The majority of patients had bilateral (n=25) or unilateral (n=8) ovarian transposition prior to radiotherapy. Nine out of 10 (90%) patients with soft tissue tumors, Ewing sarcoma or ependymoma, five out of seven (71.4%) patients with Hodgkin's lymphoma, two patients (100%) with rectal and anal cancer, and six out of 15 (40%) with cervical cancer retained ovarian function. Patients with cervical cancer, those who received concomitant chemotherapy and those older than 30 years were more likely to experience ovarian failure. Five patients conceived spontaneously and two women had four live births. CONCLUSION: Laparoscopic repositioning of the ovaries out of the radiation field in order to protect ovarian function in patients receiving radiotherapy appears to be effective in the majority of patients. The procedure seems safe and should be considered either as a sole procedure or in association with other fertility preservation methods prior to pelvic radiotherapy.

Physical and ecological effects of rehabilitating the geothermally influenced Waikite Wetland, New Zealand.

Pressure to optimise land use and to maximise the economic viability of land has had a detrimental impact on wetlands worldwide. Rehabilitating wetlands has been identified by resource managers as increasingly important to enhance environmental values and restore ecosystem functions that may have been lost through developments effecting wetlands. This paper investigates rehabilitating a geothermally influenced wetland that had been drained and used for grazing stock. The Waikite Wetland (New Zealand) is a relatively unique wetland because the primary water source to the wetland has a significant geothermal water component. This results in the area hosting populations of rare flora and fauna that are significant to New Zealand. A range of management actions that included diverting a geothermal stream back into the wetland, blocking drains, pest control, weed control, native plantings, fencing and building a weir to increase water levels were used to rehabilitate the wetland. This was done to promote thermotolerant vegetation growth, restore wetland water levels and minimise pest plant species re-establishing while minimising the effects on geothermal surface features and allowing indigenous wetland vegetation to re-establish. Physical, chemical and vegetation monitoring show that management actions have increased thermotolerant vegetation growth in the wetland while having a small potential impact on geothermal discharges into the wetland. Increasing the water level in the wetland appears to be helping control plant pest species close to the weir, but has also made sensitive vegetation growing close to the waterways more susceptible to flooding caused by high-intensity rainfall events.

Inter-observer reliability of preoperative cardiopulmonary exercise test interpretation: a cross-sectional study.

BACKGROUND: Despite the increasing importance of cardiopulmonary exercise testing (CPET) for preoperative risk assessment, the reliability of CPET interpretation is unclear. We aimed to assess inter-observer reliability of preoperative CPET. METHODS: We conducted a prospective, multi-centre, observational study of preoperative CPET interpretation. Participants were professionals with previous experience or training in CPET, assessed by a standardized questionnaire. Each participant interpreted 100 tests using standardized software. The CPET variables of interest were oxygen consumption at the anaerobic threshold (AT) and peak oxygen consumption (VO2 peak). Inter-observer reliability was measured using intra-class correlation coefficient (ICC) with a random effects model. Results are presented as ICC with 95% confidence interval, where ICC of 1 represents perfect agreement and ICC of 0 represents no agreement. RESULTS: Participants included 8/28 (28.6%) clinical physiologists, 10 (35.7%) junior doctors, and 10 (35.7%) consultant doctors. The median previous experience was 140 (inter-quartile range 55-700) CPETs. After excluding the first 10 tests (acclimatization) for each participant and missing data, the primary analysis of AT and VO2 peak included 2125 and 2414 tests, respectively. Inter-observer agreement for numerical values of AT [ICC 0.83 (0.75-0.90)] and VO2 peak [ICC 0.88 (0.84-0.92)] was good. In a post hoc analysis, inter-observer agreement for identification of the presence of a reportable AT was excellent [ICC 0.93 (0.91-0.95)] and a reportable VO2 peak was moderate [0.73 (0.64-0.80)]. CONCLUSIONS: Inter-observer reliability of interpretation of numerical values of two commonly used CPET variables was good (>80%). However, inter-observer agreement regarding the presence of a reportable value was less consistent.

Creating tissue on chip constructs in microtitre plates for drug discovery.

We report upon a novel coplanar dielectrophoresis (DEP) based cell patterning system for generating transferrable hepatic cell constructs, resembling a liver-lobule, in culture. The use of paper reinforced gel substrates provided sufficient strength to enable these constructs to be transfered into 96-well plates for long term functional studies, including in the future, drug development studies. Experimental results showed that hepatic cells formed DEP field-induced structures corresponding to an array of lobule-mimetic patterns. Hepatic viability was observed over a period of 3 days by the use of a fluorescent cell staining technique, whilst the liver specific functionality of albumin secretion showed a significant enhancement due to the layer patterning of cell lines (HepG2/C3A), compared to 2D patterned cells and un-patterned control. This "build and transfer" concept could, in future, also be adapted for the layer-by-layer construction of organs-on-chip in microtitre formats.

Do health care providers trust product monograph information regarding use of vaccines in pregnancy? A qualitative study.

BACKGROUND: Influenza immunization is recommended in pregnancy to prevent severe infections in pregnant women and newborns, yet vaccine uptake remains low. Studies suggest that cautionary language in vaccine product monographs regarding safety and use in pregnancy affects health care providers' perceptions of vaccine safety and how they counsel pregnant women. OBJECTIVE: To conduct a qualitative analysis of health care provider perceptions of the safety of inactivated influenza vaccines and their recommendations for use in pregnancy based on product monograph language statements. METHODS: Health care providers were recruited at two international health conferences and from teaching programs in Ethiopia, Ghana, Uganda, and Laos during September and October 2015. After reading the product monograph excerpts for three licensed inactivated influenza vaccines, participants completed a ten-item online survey with quantitative and qualitative components that captured perceptions of vaccine safety. RESULTS: Health care providers identified a lack of trust in manufacturers' and product monograph information. They perceived product monograph language as ambiguous and not "up-to-date" with current evidence. Health care providers wanted product monograph language that clearly conveyed evidence for the risks and benefits of the vaccine in an understandable manner. CONCLUSION: This study suggests that adopting best practices in the wording of product monographs would help to support evidence-based use of vaccines in pregnant women.

Are we close to the ideal intravenous fluid?

The approach to i.v. fluid therapy for hypovolaemia may significantly influence outcomes for patients who experience a systemic inflammatory response after sepsis, trauma, or major surgery. Currently, there is no single i.v. fluid agent that meets all the criteria for the ideal treatment for hypovolaemia. The physician must choose the best available agent(s) for each patient, and then decide when and how much to administer. Findings from large randomized trials suggest that some colloid-based fluids, particularly starch-based colloids, may be harmful in some situations, but it is unclear whether they should be withdrawn from use completely. Meanwhile, crystalloid fluids, such as saline 0.9% and Ringer's lactate, are more frequently used, but debate continues over which preparation is preferable. Perhaps most importantly, it remains unclear how to select the optimal dose of fluid in different patients and different clinical scenarios. There is good reason to believe that both inadequate and excessive i.v. fluid administration may lead to poor outcomes, including increased risk of infection and organ dysfunction, for hypovolaemic patients. In this review, we summarize the current knowledge on this topic and identify some key pitfalls and some areas of agreed best practice.

Measuring acute postoperative pain using the visual analog scale: the minimal clinically important difference and patient acceptable symptom state.

Background: The 100 mm visual analog scale (VAS) score is widely used to measure pain intensity after surgery. Despite this widespread use, it is unclear what constitutes the minimal clinically important difference (MCID); that is, what minimal change in score would indicate a meaningful change in a patient's pain status. Methods: We enrolled a sequential, unselected cohort of patients recovering from surgery and used a VAS to quantify pain intensity. We compared changes in the VAS with a global rating-of-change questionnaire using an anchor-based method and three distribution-based methods (0.3 sd , standard error of the measurement, and 5% range). We then averaged the change estimates to determine the MCID for the pain VAS. The patient acceptable symptom state (PASS) was defined as the 25th centile of the VAS corresponding to a positive patient response to having made a good recovery from surgery. Results: We enrolled 224 patients at the first postoperative visit, and 219 of these were available for a second interview. The VAS scores improved significantly between the first two interviews. Triangulation of distribution and anchor-based methods resulted in an MCID of 9.9 for the pain VAS, and a PASS of 33. Conclusions: Analgesic interventions that provide a change of 10 for the 100 mm pain VAS signify a clinically important improvement or deterioration, and a VAS of 33 or less signifies acceptable pain control (i.e. a responder), after surgery.

Correction: Identification of Novel Pre-Erythrocytic Malaria Antigen Candidates for Combination Vaccines with Circumsporozoite Protein.

[This corrects the article DOI: 10.1371/journal.pone.0159449.].

Mining balance disorders' data for the development of diagnostic decision support systems.

In this work we present the methodology for the development of the EMBalance diagnostic Decision Support System (DSS) for balance disorders. Medical data from patients with balance disorders have been analysed using data mining techniques for the development of the diagnostic DSS. The proposed methodology uses various data, ranging from demographic characteristics to clinical examination, auditory and vestibular tests, in order to provide an accurate diagnosis. The system aims to provide decision support for general practitioners (GPs) and experts in the diagnosis of balance disorders as well as to provide recommendations for the appropriate information and data to be requested at each step of the diagnostic process. Detailed results are provided for the diagnosis of 12 balance disorders, both for GPs and experts. Overall, the reported accuracy ranges from 59.3 to 89.8% for GPs and from 74.3 to 92.1% for experts.

Where are we in our understanding of the association between narcolepsy and one of the 2009 adjuvanted influenza A (H1N1) vaccines?

Evaluating new rare serious vaccine safety signals is difficult and complex work. To further assess the observed increase in narcolepsy cases seen in Europe with the 2009 pandemic H1N1 influenza vaccine, the International Alliance for Biological Standardization (IABS) invited a wide range of experts to a one day meeting in Geneva in October 2015 to present data and to discuss the implications. The presentations covered the following topics: clinical picture of childhood narcolepsy following the 2009 H1N1 pandemic vaccination campaigns; epidemiological studies conducted to assess the risk of narcolepsy, other neurological and immune-related diseases following 2009 pandemic H1N1 influenza vaccine; potential biases influencing the different epidemiological study designs; potential genetic contribution to the development of narcolepsy; potential biological mechanisms for development of narcolepsy in this setting including the role of the virus itself, antigenic differences between the vaccines and differences in AS03-adjuvanted vaccines. The presentations were followed by fulsome roundtable discussions. Members from affected families also attended and made informal comments to round out the day's deliberations. This meeting emphasized the value added in bringing together in a neutral setting a wide range of experts and vaccine producers to discuss such a complex new serious adverse event following immunization.

The long and winding road to improving immunization rates: Sharing best practices in Canada.

Vaccines are one of the most effective ways to decrease childhood mortality. Unfortunately, however, Canada placed 28th out of 29 high-income countries in a 2013 UNICEF report that compared national uptake rates of early childhood immunizations. Work is underway to address this issue as reflected in the 2016 federal budget which highlights the importance of improving access to immunization. There are many steps that can be taken to improve vaccine uptake, such as identifying and better understanding the individual and program level factors that underlie delay or refusal to receive vaccines. However, it is challenging to find evidence and ensure its relevancy within the Canadian context. Targeted resources are needed that address the complexity of immunization along the entire continuum from vaccine manufacture through to patient uptake. Although there is a lot of information relevant to Canada, it has not been gathered together in one "go to" site and it is not curated. Canada needs a solid, easily accessible, user-friendly platform for sharing what works in immunization with health care professionals as well as parents and patients. This platform would be a major step in facilitating vaccine acceptance in Canada.