Combination of Hydrogen and Halogen Bonds in the Crystal Structures of 5-Halogeno-1H-isatin-3-oximes: Involvement of the Oxime Functionality in Halogen Bonding.

Various functional groups have been considered as acceptors for halogen bonds, but the oxime functionality has received very little attention in this context. In this study, we focus on the analysis of the hydrogen and halogen bond preferences observed in the crystal structures of 5-halogeno-1H-isatin-3-oximes. These molecules can be involved in various non-covalent interactions, and the competition between these interactions has a decisive influence on their self-organization. In particular, we were interested to see whether the crystal structures of 5-halogeno-1H-isatin-3-oximes, especially bromine- and iodine-substituted ones, are characterized by the presence of halogen bonds formed with the oxime functionality. The oxime group proved its ability to compete with the other strong donor and acceptor sites by participating in the formation of cyclic hydrogen-bonded heterosynthons oxime∙∙∙amide and Ooxime∙∙∙Br/I halogen bonds.

Effectiveness of spinal manipulation and biopsychosocial self-management compared to medical care for low back pain: a randomized trial study protocol.

BACKGROUND: Chronic low back pain (cLBP) is widespread, costly, and burdensome to patients and health systems. Little is known about non-pharmacological treatments for the secondary prevention of cLBP. There is some evidence that treatments addressing psychosocial factors in higher risk patients are more effective than usual care. However, most clinical trials on acute and subacute LBP have evaluated interventions irrespective of prognosis. METHODS: We have designed a phase 3 randomized trial with a 2 × 2 factorial design. The study is also a Hybrid type 1 trial with focus on intervention effectiveness while simultaneously considering plausible implementation strategies. Adults (n = 1000) with acute/subacute LBP at moderate to high risk of chronicity based on the STarT Back screening tool will be randomized in to 1 of 4 interventions lasting up to 8 weeks: supported self-management (SSM), spinal manipulation therapy (SMT), both SSM and SMT, or medical care. The primary objective is to assess intervention effectiveness; the secondary objective is to assess barriers and facilitators impacting future implementation. Primary effectiveness outcome measures are: (1) average pain intensity over 12 months post-randomization (pain, numerical rating scale); (2) average low back disability over 12 months post-randomization (Roland-Morris Disability Questionnaire); (3) prevention of cLBP that is impactful at 10-12 months follow-up (LBP impact from the PROMIS-29 Profile v2.0). Secondary outcomes include: recovery, PROMIS-29 Profile v2.0 measures to assess pain interference, physical function, anxiety, depression, fatigue, sleep disturbance, and ability to participate in social roles and activities. Other patient-reported measures include LBP frequency, medication use, healthcare utilization, productivity loss, STarT Back screening tool status, patient satisfaction, prevention of chronicity, adverse events, and dissemination measures. Objective measures include the Quebec Task Force Classification, Timed Up & Go Test, the Sit to Stand Test, and the Sock Test assessed by clinicians blinded to the patients' intervention assignment. DISCUSSION: By targeting those subjects at higher risk this trial aims to fill an important gap in the scientific literature regarding the effectiveness of promising non-pharmacological treatments compared to medical care for the management of patients with an acute episode of LBP and the prevention of progression to a severe chronic back problem. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03581123.

Predicting decompression surgery by applying multimodal deep learning to patients' structured and unstructured health data.

BACKGROUND: Low back pain (LBP) is a common condition made up of a variety of anatomic and clinical subtypes. Lumbar disc herniation (LDH) and lumbar spinal stenosis (LSS) are two subtypes highly associated with LBP. Patients with LDH/LSS are often started with non-surgical treatments and if those are not effective then go on to have decompression surgery. However, recommendation of surgery is complicated as the outcome may depend on the patient's health characteristics. We developed a deep learning (DL) model to predict decompression surgery for patients with LDH/LSS. MATERIALS AND METHOD: We used datasets of 8387 and 8620 patients from a prospective study that collected data from four healthcare systems to predict early (within 2 months) and late surgery (within 12 months after a 2 month gap), respectively. We developed a DL model to use patients' demographics, diagnosis and procedure codes, drug names, and diagnostic imaging reports to predict surgery. For each prediction task, we evaluated the model's performance using classical and generalizability evaluation. For classical evaluation, we split the data into training (80%) and testing (20%). For generalizability evaluation, we split the data based on the healthcare system. We used the area under the curve (AUC) to assess performance for each evaluation. We compared results to a benchmark model (i.e. LASSO logistic regression). RESULTS: For classical performance, the DL model outperformed the benchmark model for early surgery with an AUC of 0.725 compared to 0.597. For late surgery, the DL model outperformed the benchmark model with an AUC of 0.655 compared to 0.635. For generalizability performance, the DL model outperformed the benchmark model for early surgery. For late surgery, the benchmark model outperformed the DL model. CONCLUSIONS: For early surgery, the DL model was preferred for classical and generalizability evaluation. However, for late surgery, the benchmark and DL model had comparable performance. Depending on the prediction task, the balance of performance may shift between DL and a conventional ML method. As a result, thorough assessment is needed to quantify the value of DL, a relatively computationally expensive, time-consuming and less interpretable method.

The Lumbar Stenosis Prognostic Subgroups for Personalizing Care and Treatment (PROSPECTS) study: protocol for an inception cohort study.

BACKGROUND: Lumbar spinal stenosis (LSS) is a common degenerative condition that contributes to back and back-related leg pain in older adults. Most patients with symptomatic LSS initially receive non-operative care before surgical consultation. However, there is a scarcity of data regarding prognosis for patients seeking non-surgical care. The overall goal of this project is to develop and evaluate a clinically useful model to predict long-term physical function of patients initiating non-surgical care for symptomatic LSS. METHODS: This is a protocol for an inception cohort study of adults 50 years and older who are initiating non-surgical care for symptomatic LSS in a secondary care setting. We plan to recruit up to 625 patients at two study sites. We exclude patients with prior lumbar spine surgeries or those who are planning on lumbar spine surgery. We also exclude patients with serious medical conditions that have back pain as a symptom or limit walking. We are using weekly, automated data pulls from the electronic health records to identify potential participants. We then contact patients by email and telephone within 21 days of a new visit to determine eligibility, obtain consent, and enroll participants. We collect data using telephone interviews, web-based surveys, and queries of electronic health records. Participants are followed for 12 months, with surveys completed at baseline, 3, 6, and 12 months. The primary outcome measure is the 8-item PROMIS Physical Function (PF) Short Form. We will identify distinct phenotypes using PROMIS PF scores at baseline and 3, 6, and 12 months using group-based trajectory modeling. We will develop and evaluate the performance of a multivariable prognostic model to predict 12-month physical function using the least absolute shrinkage and selection operator and will compare performance to other machine learning methods. Internal validation will be conducted using k-folds cross-validation. DISCUSSION: This study will be one of the largest cohorts of individuals with symptomatic LSS initiating new episodes of non-surgical care. The successful completion of this project will produce a cross-validated prognostic model for LSS that can be used to tailor treatment approaches for patient care and clinical trials.

Nonlinear Dynamics in a Synthetic Momentum-State Lattice.

The scope of analog simulation in atomic, molecular, and optical systems has expanded greatly over the past decades. Recently, the idea of synthetic dimensions-in which transport occurs in a space spanned by internal or motional states coupled by field-driven transitions-has played a key role in this expansion. While approaches based on synthetic dimensions have led to rapid advances in single-particle Hamiltonian engineering, strong interaction effects have been conspicuously absent from most synthetic dimensions platforms. Here, in a lattice of coupled atomic momentum states, we show that atomic interactions result in large and qualitative changes to dynamics in the synthetic dimension. We explore how the interplay of nonlinear interactions and coherent tunneling enriches the dynamics of a one-band tight-binding model giving rise to macroscopic self-trapping and phase-driven Josephson dynamics with a nonsinusoidal current-phase relationship, which can be viewed as stemming from a nonlinear band structure arising from interactions.

Interactions and Mobility Edges: Observing the Generalized Aubry-André Model.

Using synthetic lattices of laser-coupled atomic momentum modes, we experimentally realize a recently proposed family of nearest-neighbor tight-binding models having quasiperiodic site energy modulation that host an exact mobility edge protected by a duality symmetry. These one-dimensional tight-binding models can be viewed as a generalization of the well-known Aubry-André model, with an energy-dependent self-duality condition that constitutes an analytical mobility edge relation. By adiabatically preparing low and high energy eigenstates of this model system and performing microscopic measurements of their participation ratio, we track the evolution of the mobility edge as the energy-dependent density of states is modified by the model's tuning parameter. Our results show strong deviations from single-particle predictions, consistent with attractive interactions causing both enhanced localization of the lowest energy state due to self-trapping and inhibited localization of high energy states due to screening. This study paves the way for quantitative studies of interaction effects on self-duality induced mobility edges.

Effects of Including Epidemiologic Data in Lumbar Spine Imaging Reports on Prescribing Non-Opioid Medications for Pain.

BACKGROUND: Information on the prevalence of common imaging findings among patients without back pain in spine imaging reports might affect pain medication prescribing for patients with back pain. Prior research on inserting this text suggested a small reduction in opioid prescribing. OBJECTIVE: To evaluate the effect of epidemiologic information in spine imaging reports on non-opioid pain medication prescribing for primary care patients with back pain. DESIGN: Post hoc analysis of the Lumbar Imaging with Reporting of Epidemiology cluster-randomized trial. PARTICIPANTS: A total of 170,680 patients aged ≥ 18 years from four healthcare systems who received thoracolumbar, lumbar, or lumbosacral spine imaging from 2013 to 2016 and had not received a prescription for non-opioid pain medication in the preceding 120 days. INTERVENTION: Text of age- and modality-specific epidemiologic benchmarks indicating the prevalence of common findings in people without back pain inserted into thoracolumbar, lumbar, or lumbosacral spine imaging reports at intervention clinics. MAIN MEASURES: Primary outcomes: any non-opioid prescription within 90 days after index imaging, overall, and by sub-class (skeletal muscle relaxants, NSAIDs, gabapentinoids, tricyclic antidepressants, benzodiazepines, duloxetine). SECONDARY OUTCOMES: count of non-opioid prescriptions within 90 days, overall, and by sub-class. KEY RESULTS: The intervention was not associated with the likelihood of patients receiving at least one prescription for new non-opioid pain-related medications, overall (adjusted OR, 1.02; 95% CI, 0.97-1.08) or by sub-class. The intervention was not associated with the number of prescriptions for any non-opioid medication (adjusted incidence rate ratio [IRR], 1.02; 95% CI, 0.99-1.04). However, the intervention was associated with more new prescriptions for NSAIDs (IRR, 1.12) and tricyclic antidepressants (IRR, 1.11). CONCLUSIONS: Inserting epidemiologic text in spine imaging reports had no effect on whether new non-opioid pain-related medications were prescribed but was associated with the number of new prescriptions for certain non-opioid sub-classes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02015455.

Providing Epidemiological Data in Lumbar Spine Imaging Reports Did Not Affect Subsequent Utilization of Spine Procedures: Secondary Outcomes from a Stepped-Wedge Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of inserting epidemiological information into lumbar spine imaging reports on subsequent nonsurgical and surgical procedures involving the thoracolumbosacral spine and sacroiliac joints. DESIGN: Analysis of secondary outcomes from the Lumbar Imaging with Reporting of Epidemiology (LIRE) pragmatic stepped-wedge randomized trial. SETTING: Primary care clinics within four integrated health care systems in the United States. SUBJECTS: 238,886 patients ≥18 years of age who received lumbar diagnostic imaging between 2013 and 2016. METHODS: Clinics were randomized to receive text containing age- and modality-specific epidemiological benchmarks indicating the prevalence of common spine imaging findings in people without low back pain, inserted into lumbar spine imaging reports (the "LIRE intervention"). The study outcomes were receiving 1) any nonsurgical lumbosacral or sacroiliac spine procedure (lumbosacral epidural steroid injection, facet joint injection, or facet joint radiofrequency ablation; or sacroiliac joint injection) or 2) any surgical procedure involving the lumbar, sacral, or thoracic spine (decompression surgery or spinal fusion or other spine surgery). RESULTS: The LIRE intervention was not significantly associated with subsequent utilization of nonsurgical lumbosacral or sacroiliac spine procedures (odds ratio [OR] = 1.01, 95% confidence interval [CI] 0.93-1.09; P = 0.79) or any surgical procedure (OR = 0.99, 95 CI 0.91-1.07; P = 0.74) involving the lumbar, sacral, or thoracic spine. The intervention was also not significantly associated with any individual spine procedure. CONCLUSIONS: Inserting epidemiological text into spine imaging reports had no effect on nonsurgical or surgical procedure utilization among patients receiving lumbar diagnostic imaging.

Nondestructive dispersive imaging of rotationally excited ultracold molecules.

A barrier to realizing the potential of molecules for quantum information science applications is a lack of high-fidelity, single-molecule imaging techniques. Here, we present and theoretically analyze a general scheme for dispersive imaging of electronic ground-state molecules. Our technique relies on the intrinsic anisotropy of excited molecular rotational states to generate optical birefringence, which can be detected through polarization rotation of an off-resonant probe laser beam. Using 23Na87Rb and 87Rb133Cs as examples, we construct a formalism for choosing the molecular state to be imaged and the excited electronic states involved in off-resonant coupling. Our proposal establishes the relevant parameters for achieving degree-level polarization rotations for bulk molecular gases, thus enabling high-fidelity nondestructive imaging. We additionally outline requirements for the high-fidelity imaging of individually trapped molecules.

Effect of Out-of-Hospital Tranexamic Acid vs Placebo on 6-Month Functional Neurologic Outcomes in Patients With Moderate or Severe Traumatic Brain Injury.

Importance: Traumatic brain injury (TBI) is the leading cause of death and disability due to trauma. Early administration of tranexamic acid may benefit patients with TBI. Objective: To determine whether tranexamic acid treatment initiated in the out-of-hospital setting within 2 hours of injury improves neurologic outcome in patients with moderate or severe TBI. Design, Setting, and Participants: Multicenter, double-blinded, randomized clinical trial at 20 trauma centers and 39 emergency medical services agencies in the US and Canada from May 2015 to November 2017. Eligible participants (N = 1280) included out-of-hospital patients with TBI aged 15 years or older with Glasgow Coma Scale score of 12 or less and systolic blood pressure of 90 mm Hg or higher. Interventions: Three interventions were evaluated, with treatment initiated within 2 hours of TBI: out-of-hospital tranexamic acid (1 g) bolus and in-hospital tranexamic acid (1 g) 8-hour infusion (bolus maintenance group; n = 312), out-of-hospital tranexamic acid (2 g) bolus and in-hospital placebo 8-hour infusion (bolus only group; n = 345), and out-of-hospital placebo bolus and in-hospital placebo 8-hour infusion (placebo group; n = 309). Main Outcomes and Measures: The primary outcome was favorable neurologic function at 6 months (Glasgow Outcome Scale-Extended score >4 [moderate disability or good recovery]) in the combined tranexamic acid group vs the placebo group. Asymmetric significance thresholds were set at 0.1 for benefit and 0.025 for harm. There were 18 secondary end points, of which 5 are reported in this article: 28-day mortality, 6-month Disability Rating Scale score (range, 0 [no disability] to 30 [death]), progression of intracranial hemorrhage, incidence of seizures, and incidence of thromboembolic events. Results: Among 1063 participants, a study drug was not administered to 96 randomized participants and 1 participant was excluded, resulting in 966 participants in the analysis population (mean age, 42 years; 255 [74%] male participants; mean Glasgow Coma Scale score, 8). Of these participants, 819 (84.8%) were available for primary outcome analysis at 6-month follow-up. The primary outcome occurred in 65% of patients in the tranexamic acid groups vs 62% in the placebo group (difference, 3.5%; [90% 1-sided confidence limit for benefit, -0.9%]; P = .16; [97.5% 1-sided confidence limit for harm, 10.2%]; P = .84). There was no statistically significant difference in 28-day mortality between the tranexamic acid groups vs the placebo group (14% vs 17%; difference, -2.9% [95% CI, -7.9% to 2.1%]; P = .26), 6-month Disability Rating Scale score (6.8 vs 7.6; difference, -0.9 [95% CI, -2.5 to 0.7]; P = .29), or progression of intracranial hemorrhage (16% vs 20%; difference, -5.4% [95% CI, -12.8% to 2.1%]; P = .16). Conclusions and Relevance: Among patients with moderate to severe TBI, out-of-hospital tranexamic acid administration within 2 hours of injury compared with placebo did not significantly improve 6-month neurologic outcome as measured by the Glasgow Outcome Scale-Extended. Trial Registration: ClinicalTrials.gov Identifier: NCT01990768.

Correlated Dynamics in a Synthetic Lattice of Momentum States.

We study the influence of atomic interactions on quantum simulations in momentum-space lattices (MSLs), where driven transitions between discrete momentum states mimic transport between sites of a synthetic lattice. Low-energy atomic collisions, which are short ranged in real space, relate to nearly infinite-ranged interactions in momentum space. However, the added exchange energy between atoms in distinguishable momentum states leads to an effectively attractive, finite-ranged interaction between atoms in momentum space. In this Letter, we observe the onset of self-trapping driven by such interactions in a momentum-space double well, paving the way for more complex many-body studies in tailored MSLs. We consider the types of phenomena that may result from these interactions, including the formation of chiral solitons in zigzag flux lattices.

Revisiting the "Golden Hour": An Evaluation of Out-of-Hospital Time in Shock and Traumatic Brain Injury.

STUDY OBJECTIVE: We evaluate patients with shock and traumatic brain injury who were previously enrolled in an out-of-hospital clinical trial to test the association between out-of-hospital time and outcome. METHODS: This was a secondary analysis of patients with shock and traumatic brain injury who were aged 15 years or older and enrolled in a Resuscitation Outcomes Consortium out-of-hospital clinical trial by 81 emergency medical services agencies transporting to 46 Level I and II trauma centers in 11 sites (May 2006 through May 2009). Inclusion criteria were systolic blood pressure less than or equal to 70 mm Hg or systolic blood pressure 71 to 90 mm Hg with pulse rate greater than or equal to 108 beats/min (shock cohort) and Glasgow Coma Scale score less than or equal to 8 (traumatic brain injury cohort); patients meeting both criteria were placed in the shock cohort. Primary outcomes were 28-day mortality (shock cohort) and 6-month Glasgow Outcome Scale-Extended score less than or equal to 4 (traumatic brain injury cohort). RESULTS: There were 778 patients in the shock cohort (26% 28-day mortality) and 1,239 patients in the traumatic brain injury cohort (53% 6-month Glasgow Outcome Scale-Extended score ≤4). Out-of-hospital time greater than 60 minutes was not associated with worse outcomes after accounting for important confounders in the shock cohort (adjusted odds ratio [aOR] 1.42; 95% confidence interval [CI] 0.77 to 2.62) or traumatic brain injury cohort (aOR 0.77; 95% CI 0.51 to 1.15). However, shock patients requiring early critical hospital resources and arriving after 60 minutes had higher 28-day mortality (aOR 2.37; 95% CI 1.05 to 5.37); this finding was not observed among a similar traumatic brain injury subgroup. CONCLUSION: Among out-of-hospital trauma patients meeting physiologic criteria for shock and traumatic brain injury, there was no association between time and outcome. However, the subgroup of shock patients requiring early critical resources and arriving after 60 minutes had higher mortality.

The effects of prehospital TXA on mortality and neurologic outcomes in patients with traumatic intracranial hemorrhage: a subgroup analysis from the prehospital TXA for TBI trial.

BACKGROUND: In the Prehospital Tranexamic Acid (TXA) for TBI Trial, TXA administered within two hours of injury in the out-of-hospital setting did not reduce mortality in all patients with moderate/severe traumatic brain injury (TBI). We examined the association between TXA dosing arms, neurologic outcome, and mortality in patients with intracranial hemorrhage (ICH) on computed tomography (CT). METHODS: This was a secondary analysis of the Prehospital Tranexamic Acid for TBI Trial (ClinicalTrials.gov [NCT01990768]) that randomized adults with moderate/severe TBI (Glasgow Coma Scale<13) and systolic blood pressure > =90 mmHg within two hours of injury to a 2-gram out-of-hospital TXA bolus followed by an in-hospital saline infusion, a 1-gram out-of-hospital TXA bolus/1-gram in-hospital TXA infusion, or an out-of-hospital saline bolus/in-hospital saline infusion (placebo). This analysis included the subgroup with ICH on initial CT. Primary outcomes included 28-day mortality, 6-month Glasgow Outcome Scale-Extended (GOSE) < = 4, and 6-month Disability Rating Scale (DRS). Outcomes were modeled using linear regression with robust standard errors. RESULTS: The primary trial included 966 patients. Among 541 participants with ICH, 28-day mortality was lower in the 2-gram TXA bolus group (17%) compared to the other two groups (1-gram bolus/1-gram infusion 26%, placebo 27%). The estimated adjusted difference between the 2-gram bolus and placebo groups was -8·5 percentage points (95% CI, -15.9 to -1.0) and between the 2-gram bolus and 1-gram bolus/1-gram infusion groups was -10.2 percentage points (95% CI, -17.6 to -2.9). DRS at 6 months was lower in the 2-gram TXA bolus group than the 1-gram bolus/1-gram infusion (estimated difference -2.1 [95% CI, -4.2 to -0.02]) and placebo groups (-2.2 [95% CI, -4.3, -0.2]). Six-month GOSE did not differ among groups. CONCLUSIONS: A 2-gram out-of-hospital TXA bolus in patients with moderate/severe TBI and ICH resulted in lower 28-day mortality and lower 6-month DRS than placebo and standard TXA dosing. LEVEL OF EVIDENCE: Therapeutic/Care Management, Level II.

The effects of timing of prehospital tranexamic acid on outcomes after traumatic brain injury: Subanalysis of a randomized controlled trial.

BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic that has shown some promise in improving outcomes in traumatic brain injury (TBI), but only when given early after injury. We examined the association between timing of prehospital TXA administration and outcomes in patients with moderate to severe TBI. METHODS: Patients enrolled in the multi-institutional, double-blind randomized prehospital TXA for TBI trial with blunt or penetrating injury and suspected TBI (Glasgow Coma Scale score ≤ 12, SBP ≥90) who received either a 2-g TXA bolus or a 1-g bolus plus 1 g 8 hour infusion within 2 hours of injury were analyzed. Outcomes were compared between early administration (<45 minutes from injury) and late administration ≥45 minutes from injury) using a χ 2 , Fischer's exact test, t test, or Mann-Whitney U test as indicated. Logistic regression examined time to drug as an independent variable. A p value less than 0.05 was considered significant. RESULTS: Six hundred forty-nine patients met inclusion criteria (354 early and 259 late). Twenty-eight-day and 6-month mortalities, 6-month Glasgow Outcome Scale-Extended, and disability rating scale scores were not different between early and late administration. Late administration was associated with higher rates of deep venous thrombosis (0.8 vs. 3.4%, p = 0.02), cerebral vasospasm (0% vs. 2%, p = 0.01), as well as prolonged EMS transport and need for a prehospital airway ( p < 0.01). CONCLUSION: In patients with moderate or severe TBI who received TXA within 2 hours of injury, no mortality benefit was observed in those who received treatment within 45 minutes of injury, although lower rates of select complications were seen. These results support protocols that recommend TXA administration within 45 minutes of injury for patients with suspected TBI. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level II.

Higher Oxygenation Is Associated with Improved Survival in Severe Traumatic Brain Injury but Not Traumatic Shock.

Pre-hospital resuscitation of critically injured patients traditionally includes supplemental oxygen therapy to address potential hypoxemia. The objective of this study was to explore the association between pre-hospital hypoxemia, hyperoxemia, and mortality in patients with traumatic brain injury (TBI) and traumatic shock. We hypothesized that both hypoxemia and hyperoxemia would be associated with increased mortality. We used the Resuscitation Outcomes Consortium Prospective Observational Prehospital and Hospital Registry for Trauma (ROC PROPHET) database of critically injured patients to identify a severe TBI cohort (pre-hospital Glasgow Coma Scale [GCS] 3-8) and a traumatic shock cohort (systolic blood pressure ≤90 mm Hg and pre-hospital GCS >8). Arterial blood gas (ABG) obtained within 30 min of hospital arrival was required for inclusion. Patients with hypoxemia (PaO2 <80 mm Hg) and hyperoxemia (PaO2 >400 mm Hg) were compared to those with normoxemia (PaO2 80-400 mm Hg) with regard to the primary outcome measure of in-hospital mortality in both the TBI and traumatic shock cohorts. Multiple logistic regression was used to calculate odds ratios (ORs) after adjustment for multiple covariables. In addition, regression spline curves were generated to estimate the risk of death as a continuous function of PaO2 levels. A total of 1248 TBI patients were included, of whom 396 (32%) died before hospital discharge. Associations between hypoxemia and increased mortality (OR, 1.8; 95% confidence interval [CI], 1.2-2.8; p = 0.008) and between hyperoxemia and decreased mortality (OR, 0.6; 95% CI, 0.4-0.9; p = 0.018) were observed. A total of 582 traumatic shock patients were included, of whom 52 (9%) died before hospital discharge. No statistically significant associations were observed between in-hospital mortality and either hypoxemia (OR, 1.0; 95% CI, 0.4-2.4; p = 0.987) or hyperoxemia (OR, 1.9; 95% CI, 0.6-5.7; p = 0.269). Among patients with severe TBI but not traumatic shock, hypoxemia was associated with an increase of in-hospital mortality and hyperoxemia was associated with a decrease of in-hospital mortality.

Effectiveness of Spinal Manipulation and Biopsychosocial Self-Management compared to Medical Care for Low Back Pain: A Randomized Trial Study Protocol.

Background Chronic low back pain (cLBP) is widespread, costly, and burdensome to patients and health systems. Little is known about non-pharmacological treatments for the secondary prevention of cLBP. There is some evidence that treatments addressing psychosocial factors in higher risk patients are more effective than usual care. However, most clinical trials on acute and subacute LBP have evaluated interventions irrespective of prognosis. Methods We have designed a phase 3 randomized trial with a 2x2 factorial design. The study is also a Hybrid type 1 trial with focus on intervention effectiveness while simultaneously considering plausible implementation strategies. Adults (n = 1000) with acute/subacute LBP at moderate to high risk of chronicity based on the STarT Back screening tool will be randomized in to 1 of 4 interventions lasting up to 8 weeks: supported self-management (SSM), spinal manipulation therapy (SMT), both SSM and SMT, or medical care. The primary objective is to assess intervention effectiveness; the secondary objective is to assess barriers and facilitators impacting future implementation. Primary effectiveness outcome measures are: (1) average pain intensity over 12 months post-randomization (pain, numerical rating scale); (2) average low back disability over 12 months post-randomization (Roland-Morris Disability Questionnaire); (3) prevention of cLBP that is impactful at 10-12 months follow-up (LBP impact from the PROMIS-29 Profile v2.0). Secondary outcomes include: recovery, PROMIS-29 Profile v2.0 measures to assess pain interference, physical function, anxiety, depression, fatigue, sleep disturbance, and ability to participate in social roles and activities. Other patient-reported measures include LBP frequency, medication use, healthcare utilization, productivity loss, STarT Back screening tool status, patient satisfaction, prevention of chronicity, adverse events, and dissemination measures. Objective measures include the Quebec Task Force Classification, Timed Up & Go Test, the Sit to Stand Test, and the Sock Test assessed by clinicians blinded to the patients' intervention assignment. Discussion By targeting those subjects at higher risk this trial aims to fill an important gap in the scientific literature regarding the effectiveness of promising non-pharmacological treatments compared to medical care for the management of patients with an acute episode of LBP and the prevention of progression to a severe chronic back problem. Trial registration: ClinicalTrials.gov Identifier: NCT03581123.

Interrater agreement in the evaluation of discrepant imaging findings with the Radpeer system.

OBJECTIVE: The Radpeer system is central to the quality assurance process in many radiology practices. Previous studies have shown poor agreement between physicians in the evaluation of their peers. The purpose of this study was to assess the reliability of the Radpeer scoring system. MATERIALS AND METHODS: A sample of 25 discrepant cases was extracted from our quality assurance database. Images were made anonymous; associated reports and identities of interpreting radiologists were removed. Indications for the studies and descriptions of the discrepancies were provided. Twenty-one subspecialist attending radiologists rated the cases using the Radpeer scoring system. Multirater kappa statistics were used to assess interrater agreement, both with the standard scoring system and with dichotomized scores to reflect the practice of further review for cases rated 3 and 4. Subgroup analyses were conducted to assess subspecialist evaluation of cases. RESULTS: Interrater agreement was slight to fair compared with that expected by chance. For the group of 21 raters, the kappa values were 0.11 (95% CI, 0.06-0.16) with the standard scoring system and 0.20 (95% CI, 0.13-0.27) with dichotomized scores. There was disagreement about whether a discrepancy had occurred in 20 cases. Subgroup analyses did not reveal significant differences in the degree of interrater agreement. CONCLUSION: The identification of discrepant interpretations is valuable for the education of individual radiologists and for larger-scale quality assurance and quality improvement efforts. Our results show that a ratings-based peer review system is unreliable and subjective for the evaluation of discrepant interpretations. Resources should be devoted to developing more robust and objective assessment procedures, particularly those with clear quality improvement goals.

Crystal structure of the complex of 2,4,6-tri-ethyl-1,3,5-tris-[(4-methyl-1H-indazol-1-yl)meth-yl]-benzene with NH4PF6.

The complex of 2,4,6-tri-ethyl-1,3,5-tris-[(4-methyl-1H-indazol-1-yl)meth-yl]-benz-ene with ammonium hexa-fluorophosphate, C39H42N6·NH4 +·PF6 -, crystallizes in the monoclinic space group P21 with two mol-ecules of the receptor, two NH4 + and two PF6 - ions in the asymmetric unit. In each of the complexes the ammonium ion resides in the cavity of the receptor mol-ecule and is fixed in its position by three N-H⋯N bonds, while the remaining hydrogen atom of the cation acts as a bifurcated binding site for N-H⋯F bonding to the counter-anion. The crystal is composed of one-dimensional supra-molecular aggregates extending along the a-axis direction.

Tranexamic acid is not inferior to placebo with respect to adverse events in suspected traumatic brain injury patients not in shock with a normal head computed tomography scan: A retrospective study of a randomized trial.

BACKGROUND: A 2-g bolus of tranexamic acid (TXA) has been shown to reduce 28-day mortality in a randomized controlled trial. This study investigates whether out-of-hospital TXA use is associated with adverse events or unfavorable outcomes in suspected traumatic brain injury (TBI) when intracranial hemorrhage (ICH) is absent on initial computed tomography. METHODS: This study used data from a 2015 to 2017, multicenter, randomized trial studying the effect of the following TXA doses on moderate to severe TBI: 2-g bolus, 1-g bolus plus 1-g infusion over 8 hours, and a placebo bolus with placebo infusion. Of the 966 participants enrolled, 395 with an initial computed tomography negative for ICH were included in this analysis. Fifteen adverse events (28-day incidence) were studied: myocardial infarction, deep vein thrombosis, seizure, pulmonary embolism, acute respiratory distress syndrome, cardiac failure, liver failure, renal failure, cerebrovascular accident, cardiac arrest, cerebral vasospasm, "any thromboembolism," hypernatremia, acute kidney injury, and infection. Other unfavorable outcomes analyzed include mortality at 28 days and 6 months, Glasgow Outcome Scale-Extended score of ≤4 at discharge and 6 months, intensive care unit-free days, ventilator-free days, hospital-free days, and combined unfavorable outcomes. In both study drug groups, the incidence of dichotomous outcomes and quantity of ordinal outcomes were compared with placebo. RESULTS: No statistically significant increase in adverse events or unfavorable outcomes was found between either TXA dosing regimen and placebo. Demographics and injury scores were not statistically different other than two methods of injury, which were overrepresented in the 1-g TXA bolus plus 1-g TXA infusion. CONCLUSION: Administration of either a 2-g TXA bolus or a 1-g TXA bolus plus 1-g TXA 8-hour infusion in suspected TBIs without ICH is not associated with increased adverse events or unfavorable outcomes. Because the out-of-hospital 2-g bolus is associated with a mortality benefit, it should be administered in suspected TBI. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level II.