Outcomes from 871,441 Consecutive Surgical Procedures without Overlap or with Maximally Permissible Non-Concurrent Overlap.

OBJECTIVE: To isolate the impact of subsumed surgery (a shorter procedure completed entirely during overlapping non-critical portions of a longer antecedent procedure) on patient outcomes. SUMMARY BACKGROUND DATA: The American College of Surgeons recently recommended the elimination of "concurrent surgery" with overlap during a procedure's critical portions. Guidelines for non-concurrent overlap have been established, but the safety of subsumed surgery remains to be examined. METHODS: All consecutive procedures from 2013 to 2021 within a multihospital academic medical center were included (n=871,441). Simple logistic regression was performed to compare postoperative events between patients undergoing non-overlap surgery (n=533,032) and completely subsumed surgery (n=11,319). Thereafter, coarsened exact matching was used to match patients with non-overlap and subsumed surgery 1:1 on CPT code, 18 demographic features, baseline health characteristics, and procedural variables (n=7,146). Exact-matched cases were subsequently limited to pairs performed by the same surgeon (n=5,028). Primary outcomes included 30-day readmission, ED visits, and reoperations. RESULTS: Univariate analysis suggested that subsumed surgery had a higher 30-day risk of readmission (OR 1.55, P<0.0001), ED evaluation (OR 1.19, P<0.0001), and reoperation (OR 1.98, P<0.0001). When comparison was limited to the exact same procedure and patients were matched on demographics and health characteristics, there were no outcome differences between patients with subsumed surgery and non-overlapping surgery, even when limiting analyses to the same surgeon. CONCLUSIONS: Similar surgeries for similar patients result in similar outcomes whether there is completely subsumed or no overlap. Individual surgeons performing a specific procedure have no outcome differences with subsumed and non-overlapping cases.

Mapping hippocampal and thalamic atrophy in epilepsy: A 7-T magnetic resonance imaging study.

OBJECTIVE: Epilepsy patients are often grouped together by clinical variables. Quantitative neuroimaging metrics can provide a data-driven alternative for grouping of patients. In this work, we leverage ultra-high-field 7-T structural magnetic resonance imaging (MRI) to characterize volumetric atrophy patterns across hippocampal subfields and thalamic nuclei in drug-resistant focal epilepsy. METHODS: Forty-two drug-resistant epilepsy patients and 13 controls with 7-T structural neuroimaging were included in this study. We measured hippocampal subfield and thalamic nuclei volumetry, and applied an unsupervised machine learning algorithm, Latent Dirichlet Allocation (LDA), to estimate atrophy patterns across the hippocampal subfields and thalamic nuclei of patients. We studied the association between predefined clinical groups and the estimated atrophy patterns. Additionally, we used hierarchical clustering on the LDA factors to group patients in a data-driven approach. RESULTS: In patients with mesial temporal sclerosis (MTS), we found a significant decrease in volume across all ipsilateral hippocampal subfields (false discovery rate-corrected p [pFDR] < .01) as well as in some ipsilateral (pFDR < .05) and contralateral (pFDR < .01) thalamic nuclei. In left temporal lobe epilepsy (L-TLE) we saw ipsilateral hippocampal and some bilateral thalamic atrophy (pFDR < .05), whereas in right temporal lobe epilepsy (R-TLE) extensive bilateral hippocampal and thalamic atrophy was observed (pFDR < .05). Atrophy factors demonstrated that our MTS cohort had two atrophy phenotypes: one that affected the ipsilateral hippocampus and one that affected the ipsilateral hippocampus and bilateral anterior thalamus. Atrophy factors demonstrated posterior thalamic atrophy in R-TLE, whereas an anterior thalamic atrophy pattern was more common in L-TLE. Finally, hierarchical clustering of atrophy patterns recapitulated clusters with homogeneous clinical properties. SIGNIFICANCE: Leveraging 7-T MRI, we demonstrate widespread hippocampal and thalamic atrophy in epilepsy. Through unsupervised machine learning, we demonstrate patterns of volumetric atrophy that vary depending on disease subtype. Incorporating these atrophy patterns into clinical practice could help better stratify patients to surgical treatments and specific device implantation strategies.

iEEG-recon: A fast and scalable pipeline for accurate reconstruction of intracranial electrodes and implantable devices.

OBJECTIVE: Clinicians use intracranial electroencephalography (iEEG) in conjunction with noninvasive brain imaging to identify epileptic networks and target therapy for drug-resistant epilepsy cases. Our goal was to promote ongoing and future collaboration by automating the process of "electrode reconstruction," which involves the labeling, registration, and assignment of iEEG electrode coordinates on neuroimaging. We developed a standalone, modular pipeline that performs electrode reconstruction. We demonstrate our tool's compatibility with clinical and research workflows and its scalability on cloud platforms. METHODS: We created iEEG-recon, a scalable electrode reconstruction pipeline for semiautomatic iEEG annotation, rapid image registration, and electrode assignment on brain magnetic resonance imaging (MRI). Its modular architecture includes a clinical module for electrode labeling and localization, and a research module for automated data processing and electrode contact assignment. To ensure accessibility for users with limited programming and imaging expertise, we packaged iEEG-recon in a containerized format that allows integration into clinical workflows. We propose a cloud-based implementation of iEEG-recon and test our pipeline on data from 132 patients at two epilepsy centers using retrospective and prospective cohorts. RESULTS: We used iEEG-recon to accurately reconstruct electrodes in both electrocorticography and stereoelectroencephalography cases with a 30-min running time per case (including semiautomatic electrode labeling and reconstruction). iEEG-recon generates quality assurance reports and visualizations to support epilepsy surgery discussions. Reconstruction outputs from the clinical module were radiologically validated through pre- and postimplant T1-MRI visual inspections. We also found that our use of ANTsPyNet deep learning-based brain segmentation for electrode classification was consistent with the widely used FreeSurfer segmentations. SIGNIFICANCE: iEEG-recon is a robust pipeline for automating reconstruction of iEEG electrodes and implantable devices on brain MRI, promoting fast data analysis and integration into clinical workflows. iEEG-recon's accuracy, speed, and compatibility with cloud platforms make it a useful resource for epilepsy centers worldwide.

A Randomized Controlled Trial to Assess the Impact of Enhanced Recovery After Surgery on Patients Undergoing Elective Spine Surgery.

OBJECTIVE: To conduct a prospective, randomized controlled trial (RCT) of an enhanced recovery after surgery (ERAS) protocol in an elective spine surgery population. BACKGROUND: Surgical outcomes such as length of stay (LOS), discharge disposition, and opioid utilization greatly contribute to patient satisfaction and societal healthcare costs. ERAS protocols are multimodal, patient-centered care pathways shown to reduce postoperative opioid use, reduced LOS, and improved ambulation; however, prospective ERAS data are limited in spine surgery. METHODS: This single-center, institutional review board-approved, prospective RCT-enrolled adult patients undergoing elective spine surgery between March 2019 and October 2020. Primary outcomes were perioperative and 1-month postoperative opioid use. Patients were randomized to ERAS (n=142) or standard-of-care (SOC; n=142) based on power analyses to detect a difference in postoperative opioid use. RESULTS: Opioid use during hospitalization and the first postoperative month was not significantly different between groups (ERAS 112.2 vs SOC 117.6 morphine milligram equivalent, P =0.76; ERAS 38.7% vs SOC 39.4%, P =1.00, respectively). However, patients randomized to ERAS were less likely to use opioids at 6 months postoperatively (ERAS 11.4% vs SOC 20.6%, P =0.046) and more likely to be discharged to home after surgery (ERAS 91.5% vs SOC 81.0%, P =0.015). CONCLUSION: Here, we present a novel ERAS prospective RCT in the elective spine surgery population. Although we do not detect a difference in the primary outcome of short-term opioid use, we observe significantly reduced opioid use at 6-month follow-up as well as an increased likelihood of home disposition after surgery in the ERAS group.

Spike patterns surrounding sleep and seizures localize the seizure-onset zone in focal epilepsy.

OBJECTIVE: Interictal spikes help localize seizure generators as part of surgical planning for drug-resistant epilepsy. However, there are often multiple spike populations whose frequencies change over time, influenced by brain state. Understanding state changes in spike rates will improve our ability to use spikes for surgical planning. Our goal was to determine the effect of sleep and seizures on interictal spikes, and to use sleep and seizure-related changes in spikes to localize the seizure-onset zone (SOZ). METHODS: We performed a retrospective analysis of intracranial electroencephalography (EEG) data from patients with focal epilepsy. We automatically detected interictal spikes and we classified different time periods as awake or asleep based on the ratio of alpha to delta power, with a secondary analysis using the recently published SleepSEEG algorithm. We analyzed spike rates surrounding sleep and seizures. We developed a model to localize the SOZ using state-dependent spike rates. RESULTS: We analyzed data from 101 patients (54 women, age range 16-69). The normalized alpha-delta power ratio accurately classified wake from sleep periods (area under the curve = .90). Spikes were more frequent in sleep than wakefulness and in the post-ictal compared to the pre-ictal state. Patients with temporal lobe epilepsy had a greater wake-to-sleep and pre- to post-ictal spike rate increase compared to patients with extra-temporal epilepsy. A machine-learning classifier incorporating state-dependent spike rates accurately identified the SOZ (area under the curve = .83). Spike rates tended to be higher and better localize the seizure-onset zone in non-rapid eye movement (NREM) sleep than in wake or REM sleep. SIGNIFICANCE: The change in spike rates surrounding sleep and seizures differs between temporal and extra-temporal lobe epilepsy. Spikes are more frequent and better localize the SOZ in sleep, particularly in NREM sleep. Quantitative analysis of spikes may provide useful ancillary data to localize the SOZ and improve surgical planning.

Long-term epilepsy outcome dynamics revealed by natural language processing of clinic notes.

OBJECTIVE: Electronic medical records allow for retrospective clinical research with large patient cohorts. However, epilepsy outcomes are often contained in free text notes that are difficult to mine. We recently developed and validated novel natural language processing (NLP) algorithms to automatically extract key epilepsy outcome measures from clinic notes. In this study, we assessed the feasibility of extracting these measures to study the natural history of epilepsy at our center. METHODS: We applied our previously validated NLP algorithms to extract seizure freedom, seizure frequency, and date of most recent seizure from outpatient visits at our epilepsy center from 2010 to 2022. We examined the dynamics of seizure outcomes over time using Markov model-based probability and Kaplan-Meier analyses. RESULTS: Performance of our algorithms on classifying seizure freedom was comparable to that of human reviewers (algorithm F1 = .88 vs. human annotator κ = .86). We extracted seizure outcome data from 55 630 clinic notes from 9510 unique patients written by 53 unique authors. Of these, 30% were classified as seizure-free since the last visit, 48% of non-seizure-free visits contained a quantifiable seizure frequency, and 47% of all visits contained the date of most recent seizure occurrence. Among patients with at least five visits, the probabilities of seizure freedom at the next visit ranged from 12% to 80% in patients having seizures or seizure-free at the prior three visits, respectively. Only 25% of patients who were seizure-free for 6 months remained seizure-free after 10 years. SIGNIFICANCE: Our findings demonstrate that epilepsy outcome measures can be extracted accurately from unstructured clinical note text using NLP. At our tertiary center, the disease course often followed a remitting and relapsing pattern. This method represents a powerful new tool for clinical research with many potential uses and extensions to other clinical questions.

Meaningful coproduction with clinicians: establishing a practice-based research network with physiotherapists in regional Australia.

BACKGROUND: The disconnect between research and clinical practice leads to research evidence that is often not useful for clinical practice. Practice-based research networks are collaborations between researchers and clinicians aimed at coproducing more useful research. Such networks are rare in the physiotherapy field. We aimed to describe (i) clinicians' motivations behind, and enablers to, participating in a network, (ii) the process of network establishment and (iii) research priorities for a practice-based network of physiotherapists in the Hunter Region of New South Wales (NSW), Australia that supports research coproduction. METHODS: We describe the methods and outcomes of the three steps we used to establish the network. Step 1 involved consultation with local opinion leaders and a formative evaluation to understand clinicians' motivations behind, and enablers to, participating in a network. Step 2 involved establishment activities to generate a founding membership group and codesign a governance model. Step 3 involved mapping clinical problems through a workshop guided by systems thinking theory with local stakeholders and prioritizing research areas. RESULTS: Through formative evaluation focus groups, we generated five key motivating themes and three key enablers for physiotherapists' involvement in the network. Establishment activities led to a founding membership group (n = 29, 67% from private practice clinics), a network vision and mission statement, and a joint governance group (9/13 [70%] are private practice clinicians). Our problem-mapping and prioritization process led to three clinically relevant priority research areas with the potential for significant change in practice and patient outcomes. CONCLUSIONS: Clinicians are motivated to break down traditional siloed research generation and collaborate with researchers to solve a wide array of issues with the delivery of care. Practice-based research networks have promise for both researchers and clinicians in the common goal of improving patient outcomes.

Telehealth for opioid use disorder: retention as a function of demographics and rurality.

Background: Despite lifesaving medications such as buprenorphine and methadone, the majority of individuals with opioid use disorder (OUD) face access barriers to evidence-based treatment. COVID-19 era regulatory reforms have shown that telehealth can improve access to care, although disparities in clinical outcomes are likely to persist.Objective: We aimed to analyze 180-day and 365-day retention in treatment with buprenorphine for OUD overall and by demographics, hypothesizing that retention would be lower among racial/ethnic minorities and rural patients.Methods: We analyzed data from a cohort of individuals with OUD enrolled in treatment from April 1, 2020 to September 30, 2021, in Pennsylvania and New York using a virtual-first telehealth OUD treatment platform to assess rates of 180-day and 365-day retention. Associations between demographic characteristics and retention were assessed using unadjusted and adjusted logistic regression models.Results: Among 1,378 patients (58.8% male), 180-day retention was 56.4%, and 365-day retention was 48.3%. Adjusted analyses found that only an association between older age and greater odds of 180-day retention was significant (aOR for patients aged 30-50 vs. <30: 1.83 [1.37-2.45]). There were no significant associations between sex, race/ethnicity, state, or rurality with retention.Conclusion: While we were unable to control for socioeconomic variables, we found retention within telehealth services for buprenorphine was high irrespective of geography or race/ethnicity, but disparities with age indicate a subset of patients who may benefit from more intensive services early in care.

Multiplexed and Extraction-Free Amplification for Simplified SARS-CoV-2 RT-PCR Tests.

The rapid onset of the global COVID-19 pandemic has led to challenges for accurately diagnosing the disease, including supply shortages for sample collection, preservation, and purification. Currently, most diagnostic tests require RNA extraction and detection by RT-PCR; however, extraction is expensive and time-consuming and requires technical expertise. With these challenges in mind, we report extraction-free, multiplexed amplification of SARS-CoV-2 RNA from 246 clinical samples, resulting in 86% sensitivity and 100% specificity. The multiplex RT-PCR uses the CDC singleplex targets and has an LoD of 2 c/µL. We also report on amplification using a range of master mixes in different transport media. This work can help guide which combinations of reagents will enable accurate results when availability of supplies changes throughout the pandemic. Implementing these methods can reduce complexity and cost, minimize reagent usage, expedite time to results, and increase testing capacity.

Novel methyllycaconitine analogues selective for the α4ß2 over α7 nicotinic acetylcholine receptors.

Analogues of methyllycaconitine (MLA) based on a (3-ethyl-9-methylidene-3-azabicyclo[3.3.1]nonan-1-yl)methanol template have been designed and synthesised that incorporate the modified ester sidechains distinct from that present in the natural product. Electrophysiology experiments using Xenopus oocytes expressing nicotinic acetylcholine receptors (nAChRs) revealed selected analogues served as non-competitive inhibitors that showed selectivity for the α4ß2 over α7 nAChR subtypes, and selectivity for the (α4)3(ß2)2 over (α4)2(ß2)3 stoichiometry. This study more clearly defines the biological effects of MLA analogues and identifies strategies for the development of MLA analogues as selective ligands for the α4ß2 nAChR subtype.

Recoded organisms engineered to depend on synthetic amino acids.

Genetically modified organisms (GMOs) are increasingly used in research and industrial systems to produce high-value pharmaceuticals, fuels and chemicals. Genetic isolation and intrinsic biocontainment would provide essential biosafety measures to secure these closed systems and enable safe applications of GMOs in open systems, which include bioremediation and probiotics. Although safeguards have been designed to control cell growth by essential gene regulation, inducible toxin switches and engineered auxotrophies, these approaches are compromised by cross-feeding of essential metabolites, leaked expression of essential genes, or genetic mutations. Here we describe the construction of a series of genomically recoded organisms (GROs) whose growth is restricted by the expression of multiple essential genes that depend on exogenously supplied synthetic amino acids (sAAs). We introduced a Methanocaldococcus jannaschii tRNA:aminoacyl-tRNA synthetase pair into the chromosome of a GRO derived from Escherichia coli that lacks all TAG codons and release factor 1, endowing this organism with the orthogonal translational components to convert TAG into a dedicated sense codon for sAAs. Using multiplex automated genome engineering, we introduced in-frame TAG codons into 22 essential genes, linking their expression to the incorporation of synthetic phenylalanine-derived amino acids. Of the 60 sAA-dependent variants isolated, a notable strain harbouring three TAG codons in conserved functional residues of MurG, DnaA and SerS and containing targeted tRNA deletions maintained robust growth and exhibited undetectable escape frequencies upon culturing ∼10(11) cells on solid media for 7 days or in liquid media for 20 days. This is a significant improvement over existing biocontainment approaches. We constructed synthetic auxotrophs dependent on sAAs that were not rescued by cross-feeding in environmental growth assays. These auxotrophic GROs possess alternative genetic codes that impart genetic isolation by impeding horizontal gene transfer and now depend on the use of synthetic biochemical building blocks, advancing orthogonal barriers between engineered organisms and the environment.

Willingness to use a wearable device capable of detecting and reversing overdose among people who use opioids in Philadelphia.

BACKGROUND: The incidence of opioid-related overdose deaths has been rising for 30 years and has been further exacerbated amidst the COVID-19 pandemic. Naloxone can reverse opioid overdose, lower death rates, and enable a transition to medication for opioid use disorder. Though current formulations for community use of naloxone have been shown to be safe and effective public health interventions, they rely on bystander presence. We sought to understand the preferences and minimum necessary conditions for wearing a device capable of sensing and reversing opioid overdose among people who regularly use opioids. METHODS: We conducted a combined cross-sectional survey and semi-structured interview at a respite center, shelter, and syringe exchange drop-in program in Philadelphia, Pennsylvania, USA, during the COVID-19 pandemic in August and September 2020. The primary aim was to explore the proportion of participants who would use a wearable device to detect and reverse overdose. Preferences regarding designs and functionalities were collected via a questionnaire with items having Likert-based response options and a semi-structured interview intended to elicit feedback on prototype designs. Independent variables included demographics, opioid use habits, and previous experience with overdose. RESULTS: A total of 97 adults with an opioid use history of at least 3 months were interviewed. A majority of survey participants (76%) reported a willingness to use a device capable of detecting an overdose and automatically administering a reversal agent upon initial survey. When reflecting on the prototype, most respondents (75.5%) reported that they would wear the device always or most of the time. Respondents indicated discreetness and comfort as important factors that increased their chance of uptake. Respondents suggested that people experiencing homelessness and those with low tolerance for opioids would be in greatest need of the device. CONCLUSIONS: The majority of people sampled with a history of opioid use in an urban setting were interested in having access to a device capable of detecting and reversing an opioid overdose. Participants emphasized privacy and comfort as the most important factors influencing their willingness to use such a device. TRIAL REGISTRATION: NCT04530591.

Long-term dry storage of enzyme-based reagents for isothermal nucleic acid amplification in a porous matrix for use in point-of-care diagnostic devices.

Nucleic acid amplification test (NAAT)-based point-of-care (POC) devices are rapidly growing for use in low-resource settings. However, key challenges are the ability to store the enzyme-based reagents in dry form in the device and the long-term stability of those reagents at elevated temperatures, especially where ambient temperatures could be as high as 45 °C. Here, we describe a set of excipients including a combination of trehalose, polyethylene glycol and dextran, and a method for using them that allows long-term dry storage of enzyme-based reagents for an isothermal strand displacement amplification (iSDA) reaction in a porous matrix. Various porous materials, including nitrocellulose, cellulose, and glass fiber, were tested. Co-dried reagents for iSDA always included those that amplified the ldh1 gene in Staphylococcus aureus (a polymerase and a nicking enzyme, 4 primers, dNTPs and a buffer). Reagents also either included a capture probe and a streptavidin-Au label required for lateral flow (LF) detection after amplification, or a fluorescent probe used for real-time detection. The reagents showed the best stability in a glass fiber matrix when stored in the presence of 10% trehalose and 2.5% dextran. The reagents were stable for over a year at ∼22 °C as determined by lateral flow detection and gel electrophoresis. The reagents also exhibited excellent stability after 360 h at 45 °C; the assay still detected as few as 10 copies of ldh1 gene target by lateral flow detection, and 50 copies with real-time fluorescence detection. These results demonstrate the potential for incorporation of amplification reagents in dry form in point-of-care devices for use in a wide range of settings.

Trends and characteristics of cases when serial carboxyhemoglobins are obtained.

BACKGROUND: Carboxyhemoglobin (COHb) levels are obtained when there is suspicion for carbon monoxide (CO) exposure. Serial COHb levels are sometimes obtained despite the well-established half-life of COHb with oxygen supplementation. We sought to evaluate the trends and characteristics associated with obtaining serial carboxyhemoglobin levels. METHODS: A retrospective review was performed at an academic medical center for all inpatient and emergency department cases with either single COHb or serial COHb levels from 1 April 2010 through 31 March 2015. Data collected included age, gender, pregnancy status, smoking history, encounter month, admission status, oxygen administration, fire or burn history, vital signs, presenting symptoms, hyperbaric oxygen (HBO2) therapy use, initial pH, troponin, lactate, and COHb levels. The time and change in values between serial levels were also obtained. RESULTS: 624 cases were identified, with 106 (17%) having multiple carboxyhemoglobin levels. A mean of 2.6 (range 2 - 9) serial COHb levels were obtained. The average initial COHb was 8.9%. Subsequent serial levels were obtained on average at 353, 663 and 1,095 minutes and averaged 2.8%, 1.8% and 1.1% respectively. Serial COHb levels were obtained more commonly in burn patients, those admitted to the ICU and those who had HBO2 therapy. Four patients had an increase in COHb level on serial testing. The largest increase of these was from 2.0% to 3.9%. CONCLUSION: Serial COHb levels were not infrequent in this study. No clinically significant increase in COHb was identified by serial testing. Further studies should examine the clinical utility of such practices.

Gait and Balance Measures Can Identify Change From a Cerebrospinal Fluid Tap Test in Idiopathic Normal Pressure Hydrocephalus.

OBJECTIVES: To identify in patients with idiopathic normal pressure hydrocephalus (iNPH) undergoing a cerebrospinal fluid (CSF) tap test (TT) for consideration of a ventricular peritoneal (VP) shunt: (1) gait and balance measures, which identify symptom change; (2) differences present between pre- and post-CSF TT scores between patients classified as responders and nonresponder; (3) ability of patients with iNPH to accurately quantify change in their gait and balance symptoms from a CSF TT. DESIGN: Prospective observational study. Post-CSF TT assessment was completed 2-4 hours post. SETTING: Tertiary referral neurological and neurosurgical hospital. PARTICIPANTS: Patients (N=74) with iNPH receiving a 30 mL CSF TT for consideration of a VP shunt. INTERVENTIONS: Patients underwent a battery of gait and balance measures pre- and post-CSF TT and indicated their perceived change on a global rating of change (GRC). Patients deemed to improve and offered VP shunt insertion by a neurologist or neurosurgeon were labeled responders. MAIN OUTCOME MEASURES: Performance oriented mobility assessment (Tinetti), Berg Balance Scale (BBS), timed Up and Go (TUG), 10-meter walk test (10MWT), GRC. RESULTS: Forty patients were classified responders, 34 nonresponders. Significant differences were identified for responders: Tinetti (3.88 points), TUG (3.98 seconds), 10MWT (0.08 m/sec), and BBS (5.29 points). Significant differences were found for nonresponders for the Tinetti (0.91 points) and BBS (2.06 points). Change scores for responders and nonresponders were significantly different for all tests between responders and nonresponders. GRC scores for gait (+2 for responders, 0 for nonresponders) and balance (+2.5 for responders, 0 for nonresponders) were both significantly different. CONCLUSIONS: The Tinetti, BBS, and TUG can identify change in patients undergoing a CSF TT for iNPH. Patients appear to be able to accurately identify if change has occurred.

Telehealth-based model of care redesign to facilitate local fitting and management of patients with a spinal fracture requiring a thoracic lumbar sacral orthosis in rural hospitals in New South Wales.

OBJECTIVE: To develop and implement a telehealth-based model of care for spinal fractures requiring management with thoracic lumbar sacral orthoses that eliminates the need for transfer to a metropolitan tertiary referral hospital. DESIGN: Pre-post design observational study evaluating model of care implementation. SETTING: Rural referral hospitals in a large NSW region covering metropolitan, rural and remote hospitals. PARTICIPANTS: Patients presenting with a thoracic or lumbar spine fracture requiring thoracic lumbar sacral orthoses management and rural clinicians caring for them. OUTCOME MEASURES: Number of patients managed in rural hospitals without transfer to a metropolitan tertiary referral hospital; length of stay and related cost efficiencies; clinicians' perceived skills, knowledge and confidence levels. RESULTS: Model of care was implemented with clinical and system governance processes; and educational workshops across eight rural hospitals. A total of 81 patients managed in rural hospitals under this model between July 2013 and June 2016 without transfer were included in this study. Mean length of stay reduced from nine to four days. Hospital transfers were eliminated from the patient journey, totalling 24 324 km. Workshops were attended by 71 clinicians from nine rural hospitals and survey findings indicated a significant increase in staff knowledge, skill and confidence post education. Cost efficiencies were gained by eliminating 162 inter-hospital transfers and 405 patient bed days. CONCLUSION: This model has streamlined patient journeys and reduced transfers and travel, enabling rural clinicians to provide specialised services in local communities and facilitating timely evidence-based care in local communities without any adverse events.

Multilayered genetic safeguards limit growth of microorganisms to defined environments.

Genetically modified organisms (GMOs) are commonly used to produce valuable compounds in closed industrial systems. However, their emerging applications in open clinical or environmental settings require enhanced safety and security measures. Intrinsic biocontainment, the creation of bacterial hosts unable to survive in natural environments, remains a major unsolved biosafety problem. We developed a new biocontainment strategy containing overlapping 'safeguards'-engineered riboregulators that tightly control expression of essential genes, and an engineered addiction module based on nucleases that cleaves the host genome-to restrict viability of Escherichia coli cells to media containing exogenously supplied synthetic small molecules. These multilayered safeguards maintain robust growth in permissive conditions, eliminate persistence and limit escape frequencies to <1.3 × 10(-12). The staged approach to safeguard implementation revealed mechanisms of escape and enabled strategies to overcome them. Our safeguarding strategy is modular and employs conserved mechanisms that could be extended to clinically or industrially relevant organisms and undomesticated species.

Do trauma patients with phencyclidine-positive urine drug screens have increased morbidity or mortality?

BACKGROUND: Phencyclidine (PCP) use is anecdotally associated with agitation and injury and is frequently tested for in the setting of trauma. We sought to determine characteristics of trauma patients with a PCP-positive urine immunoassay drug screen (UDS) and if they had increased levels of care or mortality. METHODS: A 5-year retrospective review of a level 1 trauma center's trauma registry identified patients with a PCP-positive UDS. This group was then compared with 2 randomly selected control groups from the same trauma registry which were matched for age and sex but differed in that one had no sEtOH detected and a negative UDS (drug-free group) whereas the other had sEtOH or an other-than-PCP-positive UDS (other-drug group). Subgroup analysis was performed comparing PCP-positive patients with undetectable sEtOH with other-drug patients with undetectable sEtOH. RESULTS: The registry contained 7770 patients of which 156 met inclusion criteria. The mean age was 33.4years (range, 19-63), and 77% were male (n=121). When compared with the other-drug group, the PCP-positive group had significantly lower injury severity score, rates of intensive care unit admission, and sEtOH. No difference was seen in vital signs, mechanism of injury, ventilator days, intensive care unit days, total hospital days, disposition, or mortality between the 3 groups. This remained true even when subgroups with negative sEtOH were compared. CONCLUSION: This study suggests that a PCP-positive UDS in the setting of trauma is not associated with increased level of care, length of stay, or mortality.