Clinical Practice Guidelines on Ordering Echocardiography Before Hip Fracture Repair Perform Differently from One Another

Background: Osteoporotic hip fractures typically occur in frail elderly patients with multiple comorbidities, and repair of the fracture within 48 h is recommended. Pre-operative evaluation sometimes involves transthoracic echocardiography (TTE) to screen for heart disease that would alter peri-operative management, yet TTE can delay surgery and is resource intensive. Evidence suggests that the use of clinical practice guidelines (CPGs) can improve care. It is unclear which guidelines are most useful in hip fracture patients. Questions/Purposes: We sought to evaluate the performance of the five commonly used CPGs in determining which patients with acute fragility hip fracture require TTE and to identify common features among high-performing CPGs that could be incorporated into care pathways. Patients and Methods: We performed a retrospective study of medical records taken from an institutional database of osteoporotic hip fracture patients to identify those who underwent pre-operative TTE. History and physical examination findings were recorded; listed indications for TTE were compared against those given in five commonly used CPGs: those from the American College of Cardiology/American Heart Association (ACC/AHA), the British Society of Echocardiography (BSE), the European Society of Cardiology and the European Society of Anaesthesiology(ESC/ESA), the Association of Anaesthetists of Great Britain and Ireland (AAGBI), and the Scottish Intercollegiate Guidelines Network (SIGN). We then calculated the performance (sensitivity and specificity) of the CPGs in identifying patients with TTE results that had the potential to change peri-operative management. Results: We identified 100 patients who underwent pre-operative TTE. Among those, the patients met criteria for TTE 32 to 66% of the time, depending on the CPG used. In 14% of those receiving TTE, the test revealed new information with the potential to change management. The sensitivity of the CPGs ranged from 71% (ESC/ESA and AAGBI) to 100% (ACC/AHA and SIGN). The CPGs\u27 specificity ranged from 37% (BSE) to 74% (ESC/ESA). The more sensitive guidelines focused on a change in clinical status in patients with known disease or clinical concern regarding new-onset disease. Conclusions: In patients requiring fixation of osteoporotic hip fractures, TTE can be useful for identifying pathologies that could directly change peri-operative management. Our data suggest that established CPGs can be safely used to identify which patients should undergo pre-operative TTE with low risk of missed pathology

Machine Learning Based Analytics for the Significance of Gait Analysis in Monitoring and Managing Lower Extremity Injuries

This study explored the potential of gait analysis as a tool for assessing post-injury complications, e.g., infection, malunion, or hardware irritation, in patients with lower extremity fractures. The research focused on the proficiency of supervised machine learning models predicting complications using consecutive gait datasets. We identified patients with lower extremity fractures at an academic center. Patients underwent gait analysis with a chest-mounted IMU device. Using software, raw gait data was preprocessed, emphasizing 12 essential gait variables. Machine learning models including XGBoost, Logistic Regression, SVM, LightGBM, and Random Forest were trained, tested, and evaluated. Attention was given to class imbalance, addressed using SMOTE. We introduced a methodology to compute the Rate of Change (ROC) for gait variables, independent of the time difference between gait analyses. XGBoost was the optimal model both before and after applying SMOTE. Prior to SMOTE, the model achieved an average test AUC of 0.90 (95% CI: [0.79, 1.00]) and test accuracy of 86% (95% CI: [75%, 97%]). Feature importance analysis attributed importance to the duration between injury and gait analysis. Data patterns showed early physiological compensations, followed by stabilization phases, emphasizing prompt gait analysis. This study underscores the potential of machine learning, particularly XGBoost, in gait analysis for orthopedic care. Predicting post-injury complications, early gait assessment becomes vital, revealing intervention points. The findings support a shift in orthopedics towards a data-informed approach, enhancing patient outcomes.Comment: 13 pages, 6 figure

Use of Mobile Learning by Resident Physicians in Botswana

With the growth of mobile health in recent years, learning through the use of mobile devices (mobile learning [mLearning]) has gained recognition as a potential method for increasing healthcare providers\u27 access to medical information and resources in resource-limited settings. In partnership with the University of Botswana School of Medicine (SOM), we have been exploring the role of smartphone-based mLearning with resident (physicians in specialty training) education. The SOM, which admitted its first class of medical students and residents in 2009, is committed to providing high-level on-site educational resources for resident physicians, even when practicing in remote locations. Seven residents were trained to use an Android-based myTouch 3G smartphone equipped with data-enabled subscriber identity module (SIM) cards and built-in camera. Phones contained locally loaded point-of-care and drug information applications, a telemedicine application that allows for the submission of cases to local mentors, and e-mail/Web access. Surveys were administered at 4 weeks and 8 weeks following distribution of phones. We found that smartphones loaded with point-of-care tools are effectively utilized by resident physicians in resource-limited settings, both for accessing point-of-care medical information at the bedside and engaging in self-directed learning at home

Cytoplasmic expression systems triggered by mRNA yield increased gene expression in post-mitotic neurons

Non-viral vectors are promising vehicles for gene therapy but delivery of plasmid DNA to post-mitotic cells is challenging as nuclear entry is particularly inefficient. We have developed and evaluated a hybrid mRNA/DNA system designed to bypass the nuclear barrier to transfection and facilitate cytoplasmic gene expression. This system, based on co-delivery of mRNA(A64) encoding for T7 RNA polymerase (T7 RNAP) with a T7-driven plasmid, produced between 10- and 2200-fold higher gene expression in primary dorsal root ganglion neuronal (DRGN) cultures isolated from Sprague–Dawley rats compared to a cytomegalovirus (CMV)-driven plasmid, and 30-fold greater expression than the enhanced T7-based autogene plasmid pR011. Cell-free assays and in vitro transfections highlighted the versatility of this system with small quantities of T7 RNAP mRNA required to mediate expression at levels that were significantly greater than with the T7-driven plasmid alone or supplemented with T7 RNAP protein. We have also characterized a number of parameters, such as mRNA structure, intracellular stability and persistence of each nucleic acid component that represent important factors in determining the transfection efficiency of this hybrid expression system. The results from this study demonstrate that co-delivery of mRNA is a promising strategy to yield increased expression with plasmid DNA, and represents an important step towards improving the capability of non-viral vectors to mediate efficient gene transfer in cell types, such as in DRGN, where the nuclear membrane is a significant barrier to transfection

A versatile reducible polycation-based system for efficient delivery of a broad range of nucleic acids

Synthetic vectors based on reducible polycations consisting of histidine and polylysine residues (HIS RPCs) were evaluated for their ability to deliver nucleic acids. Initial experiments showed that RPC-based vectors with at least 70% histidine content mediated efficient levels of gene transfer without requirement for the endosomolytic agent chloroquine. Significant gene transfer was observed in a range of cell types achieving up to a 5-fold increase in the percentage of transfected cells compared to 25 kDa PEI, a gold standard synthetic vector. In contrast to 25 kDa PEI, HIS RPCs also mediated efficient transfer of other nucleic acids, including mRNA encoding green fluorescent protein in PC-3 cells and siRNA directed against the neurotrophin receptor p75(NTR) in post-mitotic cultures of rat dorsal root ganglion cell neurons. Experiments to elevate intracellular glutathione and linear profiling of cell images captured by multiphoton fluorescent microscopy highlighted that parameters such as the molecular weight and rate of cleavage of HIS RPCs were important factors in determining transfection activity. Altogether, these results demonstrate that HIS RPCs represent a novel and versatile type of vector that can be used for efficient cytoplasmic delivery of a broad range of nucleic acids. This should enable different or a combination of therapeutic strategies to be evaluated using a single type of polycation-based vector

Efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of acute pain after orthopedic trauma: a practice management guideline from the Eastern Association for the Surgery of Trauma and the Orthopedic Trauma Association

OBJECTIVES: Fracture is a common injury after a traumatic event. The efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs) to treat acute pain related to fractures is not well established. METHODS: Clinically relevant questions were determined regarding NSAID use in the setting of trauma-induced fractures with clearly defined patient populations, interventions, comparisons and appropriately selected outcomes (PICO). These questions centered around efficacy (pain control, reduction in opioid use) and safety (non-union, kidney injury). A systematic review including literature search and meta-analysis was performed, and the quality of evidence was graded per the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. The working group reached consensus on the final evidence-based recommendations. RESULTS: A total of 19 studies were identified for analysis. Not all outcomes identified as critically important were reported in all studies, and the outcome of pain control was too heterogenous to perform a meta-analysis. Nine studies reported on non-union (three randomized control trials), six of which reported no association with NSAIDs. The overall incidence of non-union in patients receiving NSAIDs compared with patients not receiving NSAIDs was 2.99% and 2.19% (p=0.04), respectively. Of studies reporting on pain control and reduction of opioids, the use of NSAIDs reduced pain and the need for opioids after traumatic fracture. One study reported on the outcome of acute kidney injury and found no association with NSAID use. CONCLUSIONS: In patients with traumatic fractures, NSAIDs appear to reduce post-trauma pain, reduce the need for opioids and have a small effect on non-union. We conditionally recommend the use of NSAIDs in patients suffering from traumatic fractures as the benefit appears to outweigh the small potential risks

The 'lived experience' of palliative care patients in one acute hospital setting - a qualitative study

Background There is limited understanding of the ‘lived experience’ of palliative care patient within the acute care setting. Failing to engage with and understand the views of patients and those close to them, has fundamental consequences for future health delivery. Understanding ‘patient experience’ can enable care providers to ensure services are responsive and adaptive to individual patient need. Methods The aim of this study was to explore the ‘lived experience’ of a group of patients with palliative care needs who had recently been in-patients in one acute hospital trust in the north-west of England. Qualitative research using narrative interviews was undertaken, and data was analysed using thematic analysis. A sample of 20 consecutive patients complying with the inclusion/exclusion criteria were recruited and interviewed. Results Patient Sample: Of the 20 patients recruited, there was a fairly equal gender split; all had a cancer diagnosis and the majority were white British, with an age range of 43–87 years. Findings from Interviews: Overall inpatient experience was viewed positively. Individual narratives illustrated compassionate and responsive care, with the patient at the centre. Acts of compassion appeared to be expressed through the ‘little things’ staff could do for patients, i.e., time to talk, time to care, humanity and comfort measures. AHSPCT involvement resulted in perceived improvements in pain control and holistic wellbeing. However, challenges were evident, particularly regarding over-stretched staff and resources, and modes of communication, which seemed to impact on patient experience. Conclusions Listening to patients’ experiences of care across the organisation provided a unique opportunity to impact upon delivery of care. Further research should focus on exploring issues such as: why some patients within the same organisation have a positive experience of care, while others may not; how do staff attitudes and behaviours impact on the experience of care; transitions of care from hospital to home, and the role of social networks

Issues in applying multi-arm multi-stage methodology to a clinical trial in prostate cancer: the MRC STAMPEDE trial

Background: The multi-arm multi-stage (MAMS) trial is a new paradigm for conducting randomised controlled trials that allows the simultaneous assessment of a number of research treatments against a single control arm. MAMS trials provide earlier answers and are potentially more cost-effective than a series of traditionally designed trials. Prostate cancer is the most common tumour in men and there is a need to improve outcomes for men with hormone-sensitive, advanced disease as quickly as possible. The MAMS design will potentially facilitate evaluation and testing of new therapies in this and other diseases.Methods: STAMPEDE is an open-label, 5-stage, 6-arm randomised controlled trial using MAMS methodology for men with prostate cancer. It is the first trial of this design to use multiple arms and stages synchronously.Results: The practical and statistical issues faced by STAMPEDE in implementing MAMS methodology are discussed and contrasted with those for traditional trials. These issues include the choice of intermediate and final outcome measures, sample size calculations and the impact of varying the assumptions, the process for moving between trial stages, stopping accrual to each trial arm and overall, and issues around perceived trial complexity.Conclusion: It is possible to use the MAMS design to initiate and undertake large scale cancer trials. The results from STAMPEDE will not be known for some years but the lessons learned from running a MAMS trial are shared in the hope that other researchers will use this exciting and efficient method to perform further randomised controlled trials

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care