Glial immune-related pathways mediate effects of closed head traumatic brain injury on behavior and lethality in Drosophila.

In traumatic brain injury (TBI), the initial injury phase is followed by a secondary phase that contributes to neurodegeneration, yet the mechanisms leading to neuropathology in vivo remain to be elucidated. To address this question, we developed a Drosophila head-specific model for TBI termed Drosophila Closed Head Injury (dCHI), where well-controlled, nonpenetrating strikes are delivered to the head of unanesthetized flies. This assay recapitulates many TBI phenotypes, including increased mortality, impaired motor control, fragmented sleep, and increased neuronal cell death. TBI results in significant changes in the transcriptome, including up-regulation of genes encoding antimicrobial peptides (AMPs). To test the in vivo functional role of these changes, we examined TBI-dependent behavior and lethality in mutants of the master immune regulator NF-κB, important for AMP induction, and found that while sleep and motor function effects were reduced, lethality effects were enhanced. Similarly, loss of most AMP classes also renders flies susceptible to lethal TBI effects. These studies validate a new Drosophila TBI model and identify immune pathways as in vivo mediators of TBI effects.

Highly Sensitive and Selective Detection of L-Tryptophan by ECL Using Boron-Doped Diamond Electrodes.

L-tryptophan is an amino acid that is essential to the metabolism of humans. Therefore, there is a high interest for its detection in biological fluids including blood, urine, and saliva for medical studies, but also in food products. Towards this goal, we report on a new electrochemiluminescence (ECL) method for L-tryptophan detection involving the in situ production of hydrogen peroxide at the surface of boron-doped diamond (BDD) electrodes. We demonstrate that the ECL response efficiency is directly related to H2O2 production at the electrode surface and propose a mechanism for the ECL emission of L-tryptophan. After optimizing the analytical conditions, we show that the ECL response to L-tryptophan is directly linear with concentration in the range of 0.005 to 1 µM. We achieved a limit of detection of 0.4 nM and limit of quantification of 1.4 nM in phosphate buffer saline (PBS, pH 7.4). Good selectivity against other indolic compounds (serotonin, 3-methylindole, tryptamine, indole) potentially found in biological fluids was observed, thus making this approach highly promising for quantifying L-tryptophan in a broad range of aqueous matrices of interest.

Retrospective evaluation of the impact of hypoxemia during thoracic surgery in dogs on outcome: a multicenter analysis of 94 cases.

OBJECTIVE: To investigate the statistical association of severe intraoperative hypoxemia in thoracic surgery with mortality, postoperative hospitalization times and cost of care. STUDY DESIGN: Retrospective study. ANIMALS: Dogs that underwent thoracic surgery in three veterinary hospitals between October 1, 2018 and October 1, 2020. METHODS: Anesthesia and hospitalization records from 112 dogs were reviewed and 94 cases met inclusion criteria. Recorded data included signalment, disease etiology, pulmonary or extrapulmonary nature of disease, surgical procedure performed, episodes of severe intraoperative hypoxemia defined as a pulse oximetry reading (SpO2) <90% of 5 minutes or longer duration, survival to discharge, time from extubation to hospital discharge and total invoice cost for clinical visit. Dogs were divided into two groups, those that experienced severe hypoxemia (group A) and those in which SpO2 reading <90% was not observed throughout the procedure (group B). RESULTS: Group A had a greater risk of mortality (odds ratio 10.6, 95% confidence interval 1.9-106.7; p = 0.002), prolonged hospitalization (median 62 hours versus 46 hours; p = 0.035) and more expensive cost of care (median US$10,287 versus $8506; p = 0.056) than group B. No significant difference was found for the type of surgical procedure or pulmonary versus extrapulmonary nature of disease. CONCLUSIONS AND CLINICAL RELEVANCE: Severe intraoperative hypoxemia was statistically associated with an increased risk of mortality and longer postoperative hospitalization times. Although not achieving statistical significance, there was a trend toward increased costs to the client for animals with intraoperative hypoxemia.

Novel ECL Method for the Determination of Skatole in Porcine Adipose Tissue.

A new method for the determination of skatole present in porcine adipose tissue samples utilizing the electrochemiluminescence of skatole is presented. It has been observed that oxygen radicals produced at a high cathodic voltage can react with oxidized skatole to create an excited intermediate molecule that then relaxes, generating peak photon emission at around 480 nm. A strong electrochemiluminescence or electrogenerated chemiluminescence (ECL) signal using boron-doped diamond (BDD) electrodes was observed optimally when a reduction potential of -1.8 V was applied, held for 40 s, before holding an oxidation potential of 0.8 V for 10 s. Using this principle, a calibration curve using known concentrations of skatole showed good linearity (range 0.025-2 µM) and a very low detection limit (LOD, 0.7 nM). A method that demonstrates for the first time an approach that utilizes this ECL reaction, and has the potential to be developed into an analytical device for use in the slaughterhouse, has been developed. This was achieved by extracting skatole out of the porcine adipose tissues into acetonitrile - giving an extraction efficiency of 67.6%. This method was then validated by analyzing the skatole content of 33 pig fat samples that had been previously tested using a standard technique, high-performance liquid chromatography (HPLC), containing a range of concentrations (0.02-2.58 µg/g). This ECL method exhibited excellent reliability and correlation with HPLC, giving a R2 coefficient of 0.911, thus demonstrating the potential for this method to be developed for an on-line skatole detector.

Hastening Death in Canadian ICUs: End-of-Life Care in the Era of Medical Assistance in Dying.

OBJECTIVES: Since 2016, Canada has allowed for euthanasia based on strict criteria under federal medical assistance in dying legislation. The purpose of this study was to determine how Canadian intensivists perceive medical assistance in dying and whether they believe their approach to withdrawal of life-sustaining therapies has changed following introduction of medical assistance in dying. DESIGN: Electronic survey. SETTING: Participants were recruited from 11 PICU programs and 14 adult ICU programs across Canada. All program leaders for whom contact information was available were approached for participation. PARTICIPANTS: We invited intensivists and critical care trainees employed between December 2019 and May 2020 to participate using a snowball sampling technique in which department leaders distributed study information. All responses were anonymous. Quantitative data were analyzed using descriptive statistics. Categorical variables were analyzed using Pearson chi-square test. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: We obtained 150 complete questionnaires (33% response rate), of which 50% were adult practitioners and 50% pediatric. Most were from academic centers (81%, n = 121). Of respondents, 86% (n = 130) were familiar with medical assistance in dying legislation, 71% in favor, 14% conflicted, and 11% opposed. Only 5% (n = 8) thought it had influenced their approach to withdrawal of life-sustaining therapies. Half of participants had no standardized protocol for withdrawal of life-sustaining therapies in their unit, and 41% (n = 62) had observed medications given in disproportionately high doses during withdrawal of life-sustaining therapies, with 13% having personally administered such doses. Most (80%, n = 120) had experienced explicit requests from families to hasten death, and almost half (47%, n = 70) believed it was ethically permissible to intentionally hasten death following withdrawal of life-sustaining therapies. CONCLUSIONS: Most Canadian intensivists surveyed do not think that medical assistance in dying has changed their approach to end of life in the ICU. A significant minority are ethically conflicted about the current approach to assisted dying/euthanasia in Canada. Almost half believe it is ethical to intentionally hasten death during withdrawal of life-sustaining therapies if death is expected.

Simultaneous monitoring of HIV viral load and screening of SARS-CoV-2 employing a low-cost RT-qPCR test workflow.

The COVID-19 pandemic interrupted routine care for individuals living with HIV, putting them at risk of virologic failure and HIV-associated illness. Often this population is at high risk for exposure to SARS-CoV-2 infection, and once infected, for severe disease. Therefore, close monitoring of HIV plasma viral load (VL) and screening for SARS-CoV-2 infection are needed. We developed a non-proprietary method to isolate RNA from plasma, nasal secretions (NS), or both. The extracted RNA is then submitted to RT-qPCR to estimate the VL and classify HIV/SARS-CoV-2 status (i.e., HIV virologic failure or suppressed; SARS-CoV-2 as positive, presumptive positive, negative, or indeterminate). In contrived samples, the in-house RNA extraction workflow achieved a detection limit of 200-copies per mL for HIV RNA in plasma and 100-copies per mL for SARS-CoV-2 RNA in NS. Similar detection limits were observed for HIV and SARS-CoV-2 in pooled plasma/NS contrived samples. When comparing in-house with standard extraction methods, we found high agreement (>0.91) between input and measured RNA copies for HIV LTR in contrived plasma; SARS-CoV-2 N1/N2 in contrived NS; and LTR, N1, and N2 in pooled plasma/NS samples. We further evaluated this workflow on 133 clinical specimens: 40 plasma specimens (30 HIV-positive), 67 NS specimens (31 SARS-CoV-2-positive), and 26 combined plasma/NS specimens (26 HIV-positive with 10 SARS-CoV-2-positive), and compared the results obtained using the in-house RNA extraction to those using a commercial kit (standard extraction method). The in-house extraction and standard extraction of clinical specimens were positively correlated: plasma HIV VL (R2 of 0.81) and NS SARS-CoV-2 VL (R2 of 0.95 and 0.99 for N1 and N2 genes, respectively); and pooled plasma/NS HIV VL (R2 of 0.71) and SARS-CoV-2 VL (R2 of 1 both for N1 and N2 genes). Our low-cost molecular test workflow ($1.85 per pooled sample extraction) for HIV RNA and SARS-CoV-2 RNA could serve as an alternative to current standard assays ($12 per pooled sample extraction) for laboratories in low-resource settings.

Exploring parity in female authorship of pharmacoepidemiology articles: A case study of the Canadian Network for Observational Drug Effect Studies and its citing articles.

PURPOSE: The Canadian Network for Observational Drug Effect Studies (CNODES) studies the benefits and risks of post-market drugs and evaluates its research mobilization efforts for accountability, demonstrating value, and learning. As part of these evaluation efforts, and acknowledging gender disparity in authorship across many academic disciplines, CNODES examined the relationship between gender and authorship in its own journal articles and the literature citing them. METHODS: CNODES articles (published 2012-2017) and all citing articles were identified and extracted using Scopus. Scopus author IDs were used to extract full names and a web service (www.genderapi.com) was used to estimate gender, converting all probabilities <80% to "indeterminate." T-tests and visualizations were used to compare the proportion of females between CNODES and the citing literature. RESULTS: Twenty-eight CNODES articles and 463 citing articles were identified. The mean number of authors per article was 9.5 in CNODES articles and 5.7 in the citing literature. CNODES articles had a female authorship rate of 36%, compared to 29% in the citing literature (7% difference, 95% CI: [1%, 13%]). There were no female authors in 14% of CNODES articles versus 36% of the citing literature. Women were first authors in 25% and corresponding authors in 14% of CNODES articles. CONCLUSIONS: This analysis provides a benchmark and method to monitor progress in female parity in pharmacoepidemiology authorship. Further work is needed to determine and address barriers and facilitators to women's recruitment and advancement in the field of pharmacoepidemiology.

Magnitude, Direction, Temporal Patterns, and Frequency of Loss of Distal Radius Fracture Reduction in Women 50 Years and Older.

PURPOSE: To determine the magnitude, direction, temporal patterns, and frequency of reduction loss following nonsurgical, closed treatment of distal radius fractures in women 50 years and older and correlate these observations with bone mineral density and age. METHODS: We reviewed registry data on 1,148 patients 50 years and older with distal radius fractures managed by closed reduction and cast immobilization. Radial inclination (RI), ulnar variance (UV), and radial tilt (RT) were measured immediately and at 1, 2, 3, 6, 9, and 12 weeks after reduction. Magnitude, direction, frequency, and patterns of change were compared at each time point and correlated with bone mineral density T-scores and age using paired t tests in a mixed effects model. RESULTS: Over 12 weeks, RI decreased by 3° ± 5°, the majority occurring in the first 2 weeks and significantly correlated with bone mineral density T-score and age. Unexpectedly, RI increased over time in 5% of patients. Ulnar variance increased by 2.3 ± 1.7 mm, the majority occurring in the first 3 weeks and correlated with age. Radial tilt changed by 7° ± 11° in those displacing dorsally and 8° ± 12° in those displacing volarly at 12 weeks, with the majority occurring in the first 3 weeks and significantly correlating with age. Ulnar variance and RT continued to change by small increments between weeks 3 and 6. Nearly 90% of our cohort experienced measurable loss of reduction and 50% changed at least 5° RI, 11° RT, and 2 mm UV. CONCLUSIONS: Most distal radius fracture managed with closed reduction and casting have some loss of reduction, the majority occurring in the first 3 weeks and correlated with increased age and osteoporosis. This guides clinicians in informing patients about expected reduction loss, frequency of clinical and radiographic follow-up, and timing of discussions regarding the need for surgery. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

A randomized controlled trial investigating effects of an individualized pedometer driven walking program on chronic low back pain.

BACKGROUND: Walking is an easily prescribed physical activity for people with low back pain (LBP). However, the evidence for its effectiveness to improve pain and disability levels for people with chronic low back pain (CLBP) within a community setting has not been evaluated. This study evaluates the effectiveness of a clinician guided, pedometer-driven, walking intervention for increasing physical activity and improving clinical outcomes compared to education and advice. METHODS: Randomized controlled trial recruiting N = 174 adults with CLBP. Participants were randomly allocated into either a standardized care group (SG) or pedometer based walking group (WG) using minimization allocation with a 2:1 ratio to the WG. Prior to randomization all participants were given a standard package of education and advice regarding self-management and the benefits of staying active. Following randomization the WG undertook a physiotherapist guided pedometer-driven walking program for 12 weeks. This was individually tailored by weekly negotiation of daily step targets. Main outcome was the Oswestry Disability Index (ODI) recorded at baseline, 12 weeks, 6 and 12 months. Other outcomes included, numeric pain rating, International Physical Activity Questionnaire (IPAQ), Fear-Avoidance Beliefs Questionnaire (FABQ), Back Beliefs questionnaire (BBQ), Physical Activity Self-efficacy Scale, and EQ-5D-5L quality of life estimate. RESULTS: N = 138 (79%) participants completed all outcome measures at 12 weeks reducing to N = 96 (55%) at 12 months. Both observed and intention to treat analysis did not show any statistically significant difference in ODI change score between the WG and the SG at all post-intervention time points. There were also no significant between group differences for change scores in all secondary outcome measures. Post hoc sensitivity analyses revealed moderately disabled participants (baseline ODI ≥ 21.0) demonstrated a greater reduction in mean ODI scores at 12 months in the WG compared to SG, while WG participants with a daily baseline step count < 7500 steps demonstrated a greater reduction in mean ODI scores at 12 weeks. CONCLUSIONS: Overall, we found no significant difference in change of levels of (ODI) disability between the SG and WG following the walking intervention. However, ODI responses to a walking program for those with moderate levels of baseline disability and those with low baseline step count offer a potential future focus for continued research into the benefit of walking as a management strategy for chronic LBP. TRIAL REGISTRATION: United States National Institutes of Health Clinical Trails registry (http://ClinicalTrials.gov/) No. NCT02284958 (27/10/2014).

Exercise treatment effect modifiers in persistent low back pain: an individual participant data meta-analysis of 3514 participants from 27 randomised controlled trials.

BACKGROUND: Low back pain is one of the leading causes of disability worldwide. Exercise therapy is widely recommended to treat persistent non-specific low back pain. While evidence suggests exercise is, on average, moderately effective, there remains uncertainty about which individuals might benefit the most from exercise. METHODS: In parallel with a Cochrane review update, we requested individual participant data (IPD) from high-quality randomised clinical trials of adults with our two primary outcomes of interest, pain and functional limitations, and calculated global recovery. We compiled a master data set including baseline participant characteristics, exercise and comparison characteristics, and outcomes at short-term, moderate-term and long-term follow-up. We conducted descriptive analyses and one-stage IPD meta-analysis using multilevel mixed-effects regression of the overall treatment effect and prespecified potential treatment effect modifiers. RESULTS: We received IPD for 27 trials (3514 participants). For studies included in this analysis, compared with no treatment/usual care, exercise therapy on average reduced pain (mean effect/100 (95% CI) -10.7 (-14.1 to -7.4)), a result compatible with a clinically important 20% smallest worthwhile effect. Exercise therapy reduced functional limitations with a clinically important 23% improvement (mean effect/100 (95% CI) -10.2 (-13.2 to -7.3)) at short-term follow-up. Not having heavy physical demands at work and medication use for low back pain were potential treatment effect modifiers-these were associated with superior exercise outcomes relative to non-exercise comparisons. Lower body mass index was also associated with better outcomes in exercise compared with no treatment/usual care. This study was limited by inconsistent availability and measurement of participant characteristics. CONCLUSIONS: This study provides potentially useful information to help treat patients and design future studies of exercise interventions that are better matched to specific subgroups. PROTOCOL PUBLICATION: https://doi.org/10.1186/2046-4053-1-64.

Improved precision of radiographic measurements for distal radius fractures after a technique-teaching tutorial.

Background: For the management of distal radius fractures, surgical decision-making depends on radiographic measurements of indicators including radial inclination (RI), ulnar variance (UV) and radial tilt (RT). Evaluation of the inter- and intrarater reliability of surgeons' measurements of these criteria has been limited. Methods: Twelve physicians were invited to participate in this study. Anonymously, they measured RI, UV and RT on 30 digitally stored radiographs of distal radius fractures on 3 occasions, each at least 1 week apart, using online measuring tools. After taking the third set of measurements, the participants were given a tutorial by the senior author (G.J.) on a single technique to measure all 3 indicators. The participants then took 3 more sets of measurements using only the technique they had been taught. Intraclass correlation coefficients (ICCs) were used to evaluate interrater reliability each week. Multiple logistic regression was used to calculate the effect of the tutorial, controlling for week of study along with reader (participant) and patient variance. Results: The ICCs indicated that the participants' measurement precision improved promptly after the tutorial, and this improvement was sustained through subsequent readings. The odds of an "accurate" measurement (within 2° of the senior author's measurements for RI, 1 mm for UV and 4° for RT) was 1.7 times higher for RI, 2.7 times higher for UV and 2.3 times higher for RT after the tutorial; all of these results were statistically significant. Conclusion: Surgeons ought to be familiar with a method to reproducibly measure the indicators used in the published guidelines for surgical intervention. The tutorial on a single standardized technique for online measurement of RI, UV and RT in distal radius fractures improved measurement precision.

Contexte: Pour la prise en charge des fractures du radius distal, la prise de décisions chirurgicales dépend de la mesure de plusieurs indicateurs sur les images radiographiques : l'inclinaison radiale (IR), la variance ulnaire (VU) et l'inclinaison sagittale du radius (ISR). La fiabilité interévaluateurs et intra-évaluateur des mesures de ces critères par les chirurgiens a été peu étudiée. Méthodes: Nous avons invité 12 médecins à participer à l'étude. En tout anonymat, ils ont déterminé l'IR, la VU et l'ISR au moyen d'outils de mesure en ligne sur 30 radiographies numérisées de fractures du radius distal. Ils ont répété l'exercice à 3 reprises, à au moins 1 semaine d'intervalle. Après la troisième série, les participants ont suivi un tutoriel de l'auteur principal (G. J.) sur une technique qui peut à elle seule mesurer les 3 indicateurs. Les participants ont ensuite fait 3 autres séries de mesures en utilisant seulement cette technique. Nous avons évalué la fiabilité interévaluateurs pour chaque semaine à partir des coefficients de corrélation intraclasse (CCI). De plus, nous avons calculé l'effet du tutoriel par régression logistique multiple, en tenant compte de la semaine de l'étude et de la variation selon les lecteurs (participants) et les patients. Résultats: Les CCI indiquent que la précision des mesures s'est améliorée rapidement après le tutoriel; cette amélioration a d'ailleurs persisté tout au long des séries subséquentes. La probabilité d'une mesure « exacte ¼ (dont l'écart par rapport aux mesures de l'auteur principal est inférieur à 2° pour l'IR, à 1 mm pour la VU et à 4° pour l'ISR) était 1,7 fois plus grande pour l'IR, 2,7 fois plus grande pour la VU et 2,3 fois plus grande pour l'ISR après le tutoriel. Tous ces résultats sont statistiquement significatifs. Conclusion: Les chirurgiens doivent connaître une méthode de mesure reproductible des indicateurs utilisés dans les directives cliniques publiées pour guider l'intervention chirurgicale. Le tutoriel sur la technique normalisée de mesure en ligne de l'IR, de la VU et de l'ISR dans les cas de fracture du radius distal a amélioré la précision des mesures.

Structural and Functional Characterization of Dynamic Oligomerization in Burkholderia cenocepacia HMG-CoA Reductase.

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR), in most organisms, catalyzes the four-electron reduction of the thioester (S)-HMG-CoA to the primary alcohol (R)-mevalonate, utilizing NADPH as the hydride donor. In some organisms, including the opportunistic lung pathogen Burkholderia cenocepacia, it catalyzes the reverse reaction, utilizing NAD+ as a hydride acceptor in the oxidation of mevalonate. B. cenocepacia HMGR has been previously shown to exist as an ensemble of multiple non-additive oligomeric states, each with different levels of enzymatic activity, suggesting that the enzyme exhibits characteristics of the morpheein model of allostery. We have characterized a number of factors, including pH, substrate concentration, and enzyme concentration, that modulate the structural transitions that influence the interconversion among the multiple oligomers. We have also determined the crystal structure of B. cenocepacia HMGR in the hexameric state bound to coenzyme A and ADP. This hexameric assembly provides important clues about how the transition among oligomers might occur, and why B. cenocepacia HMGR, unique among characterized HMGRs, exhibits morpheein-like behavior.

Surgically positioned paravertebral catheters and postoperative analgesia after open abdominal aortic aneurysm repair.

OBJECTIVE: To compare postoperative morphine equivalent intake after open abdominal aortic aneurysm (AAA) repair among analgesic modalities: systemic analgesia (SA) only with no regional anesthesia, surgically positioned paravertebral catheter (PVC), and thoracic epidural analgesia (TEA). METHODS: This retrospective cohort study included patients undergoing elective open AAA at the Queen Elizabeth II Health Science Center, Halifax, Nova Scotia. Demographics, morphine equivalents, methods of analgesia administration, and outcomes data were collected on all patients from 2005 to 2016. Total morphine equivalent (MEQ) on postoperative days (PODs) 1, 2, and 3 were compared among patients with SA, PVC, and TEA. A multivariable zero-inflated log-linear regression was used to determine the association between analgesic modality and MEQ. Multivariable logistic regression models were used to determine associations between analgesic modality and postoperative pain, rates of discharge from intensive care within 1 day and opioid-related adverse events. RESULTS: The study cohort included 355 patients: 177 retroperitoneal and 178 transperitoneal repairs; 173 patients underwent SA, 117 PVC, and 65 TEA. On POD1, median MEQs were 984 (interquartile range [IQR], 342-1525) for SA, 89 (33-246) for PVC, and 49 (0-90) for TEA. On POD2, the median MEQs were 105 (IQR, 57-210) for SA, 45 (15-99) for PVC, and 30 (0-64) for TEA. On POD3, the median MEQs were 45 (IQR, 15-120) for SA, 30 (0-60) for PVC, and 10 (0-45) for TEA. On multivariable log-linear regression, compared with SA, PVC and TEA were associated with increased odds of receiving no opioids on POD1 (odds ratio [OR], 66.85; 95% confidence interval [CI], 17.49-255.57; and OR, 214.68; 95% CI, 60.20-766.38; respectively), POD 2 (OR, 6.97; 95% CI, 3.61-13.46; and OR, 28.73; 95% CI, 15.68-52.62; respectively), and POD 3 (OR, 3.93; 95% CI, 2.72-5.67; and OR, 4.68; 95% CI, 3.20-6.86; respectively). If patients did receive opioids, compared with SA, PVC and TEA were associated with decreased consumption on POD1 (RR, 0.22; 95% CI, 0.18-0.27; and RR, 0.16; 95% CI, 0.12-0.20; respectively), POD2 (RR, 0.50; 95% CI, 0.42-0.58; and RR, 0.46; 95% CI, 0.37-0.56; respectively), and POD3 (RR, 0.78; 95% CI, 0.66-0.93; and RR, 0.76; 95% CI, 0.63-0.93; respectively). Compared with SA, PVC was associated with earlier discharge from intensive care (OR, 2.75; 95% CI, 1.17-6.45) and TEA was not (OR, 1.12; 95% CI, 0.56-2.2). Compared with TEA, PVC was not associated with increased rate of opioid-related adverse events (OR, 0.44; 95% CI, 0.08-2.44). CONCLUSIONS: PVC and TEA are associated with decreased MEQ compared with SA. PVC is associated with earlier discharge from intensive care compared with SA and similar rates of opioid-related adverse events compared with TEA. Paravertebral analgesia appears to be a safe and effective analgesic modality in patients undergoing retroperitoneal approach for abdominal aneurysm repair.

Clinical Course of Relapsing Remitting Multiple Sclerosis Post-Natalizumab.

Natalizumab is an efficacious disease modifying therapy (DMT) for relapsing remitting multiple sclerosis (RRMS), often limited by risk of progressive multifocal leukoencephalopathy. We describe the clinical course of RRMS patients switched from natalizumab to another DMT. We identified all RRMS patients treated with natalizumab ≥3 months with JC virus antibody positivity who switched to another DMT. Overall, 84 individuals switched DMT with 57 (68%) beginning fingolimod. On fingolimod, survival without a relapse was 74% (55.8-85.6%) at 36 months and survival without disease progression was 78% (62.6-87.6%) at 36 months. In conclusion, fingolimod is an effective therapy post-natalizumab.

L'évolution clinique de patients atteints de la forme cyclique de la sclérose en plaques ayant opté pour un traitement autre que celui au natalizumab. Le natalizumab est un médicament modificateur de l'évolution de la sclérose en plaques (MMSP) efficace pour le traitement de la sclérose en plaques récurrente-rémittente (SEP-RR), souvent limité par le risque de la leucoencéphalopathie multifocale progressive. Nous décrivons l'évolution clinique des patients atteints de SEP-RR qui sont passés du natalizumab à un autre MMSP. Nous avons identifié tous les patients atteints de SEP-RR ayant été traités avec le natalizumab ≥3 mois avec la positivité des anticorps anti-virus JC et ayant opté pour un autre MMSP. Globalement, 84 personnes ont changé de MMSP avec 57 (68%) ayant changé au fingolimod. Parmi les patients sous le fingolimod, la survie sans rechute était de 74% (55,8 à 85,6%) à 36 mois et la survie sans progression était de 78% (62,6 à 87,6%) à 36 mois. En conclusion, le fingolimod est une thérapie post-natalizumab efficace.

After Childhood Cancer: a Qualitative Study of Family Physician, Parent/Guardian, and Survivor Information Needs and Perspectives on Long-Term Follow-up and Survivorship Care Plans.

Despite support for the provision of a survivorship care plan (SCP) to every cancer survivor, there is a lack of understanding of the needs and preferences of key stakeholders. We examined perspectives of a novel personalized SCP for childhood cancer survivors (CCS), their family, and family physicians (FP). We conducted semi-structured telephone interviews with a purposefully selected sample of CCS, parents/guardians, and FPs. Data included responses to stakeholder cancer care information needs, concerns with or gaps in communication, the perceived role of the FP in the long-term management of CCS care, utility of the SCP, preferred format, and suggestions for improvement. A deductive content analysis was conducted. Twenty-four participants including 8 CCS, 10 parents/guardians, and 6 FPs completed an interview. Four main and several sub-categories emerged. Core categories were coded as (1) informative reference, (2) coordination of follow-up, (3) barriers to follow-up care, and (4) suggestions for improvement and future implementation. The majority of participants preferred an electronic- or web-based format. Overall, the SCP was seen as an informative and concise resource. The SCP was thought to be a valuable tool to foster communication and empower CCSs to become more fully engaged in their own cancer-related health care. FPs viewed the SCP as a useful resource to facilitate and guide the long-term management of the CCS. In addition to the treatment summary, a comprehensive follow-up timeline, personalized lifestyle information, and details on how to access additional psychosocial support were highlighted as important components.

Web-Based Tool for Standardized Reporting of Thyroid Ultrasound Studies.

OBJECTIVE: Our objective was to create a user-friendly synoptically driven web-based tool for radiologists to report thyroid ultrasound studies and thereby improve the quality, completeness, and recommendations of reports. CONCLUSION: The tool, developed using JavaScript and PHP (hypertext preprocessor), provides radiologists with a way to generate complete thyroid ultrasound reports and automatically categorize thyroid nodules of varying suspicion. Future work will focus on integration with the radiology information system for seamless reporting and the development of a prospective database.

Intrarater Reliability of Range of Motion Measurements of the Uninjured Wrist in Women After Distal Radius Fracture.

PURPOSE: To determine the intrarater reliability of serial wrist and forearm range of motion (ROM) measurements of the uninjured limb, by 1 evaluator using a standardized technique of measurement, in women who have sustained a distal radius fracture. METHODS: From December 2007 to December 2014, skeletally mature women who had sustained an isolated distal radius fracture routinely had sequential measurements of wrist extension and flexion as well as forearm supination and pronation in both their injured and their uninjured limbs, at a minimum of 3-week intervals. The senior author (G.H.F.J.) used a standardized technique of measurement of ROM throughout this period, and these data related to the uninjured wrist and forearm were retrospectively reviewed. RESULTS: Of 508 women who had a distal radius fracture, 506 had the measurements made of the uninjured wrist and forearm on 2, 300 on 3, and 128 on 4 separate occasions. The average age of the women was 61 years, with a range from 16 to 94 years. The intraclass correlation coefficients between measurements over time for extension, flexion, and supination measurements were 0.71, 0.63, 0.68, respectively, and 0.47 for pronation. The intraclass correlation coefficient varied according to patient age, but without specific progression in any age group for any ROM. Extension, flexion, and supination decreased significantly as age increased, whereas forearm pronation did not. CONCLUSIONS: Measurement of wrist and forearm motion of the uninjured limb can be reliably reproduced by a single rater, most so for extension, flexion, and supination, and less so for pronation. Interrater reliability assessment remains to be evaluated. CLINICAL RELEVANCE: Given the intrarater reliability of wrist and forearm motion measurement, the opposite (uninjured) wrist probably represents a useful reference metric for motion restoration for recovery from injury to the opposite limb.

Prophylactic radiotherapy for the prevention of procedure-tract metastases after surgical and large-bore pleural procedures in malignant pleural mesothelioma (SMART): a multicentre, open-label, phase 3, randomised controlled trial.

BACKGROUND: The use of prophylactic radiotherapy to prevent procedure-tract metastases (PTMs) in malignant pleural mesothelioma remains controversial, and clinical practice varies worldwide. We aimed to compare prophylactic radiotherapy with deferred radiotherapy (given only when a PTM developed) in a suitably powered trial. METHODS: We did a multicentre, open-label, phase 3, randomised controlled trial in 22 UK hospitals of patients with histocytologically proven mesothelioma who had undergone large-bore pleural interventions in the 35 days prior to recruitment. Eligible patients were randomised (1:1), using a computer-generated sequence, to receive immediate radiotherapy (21 Gy in three fractions within 42 days of the pleural intervention) or deferred radiotherapy (same dose given within 35 days of PTM diagnosis). Randomisation was minimised by histological subtype, surgical versus non-surgical procedure, and pleural procedure (indwelling pleural catheter vs other). The primary outcome was the incidence of PTM within 7 cm of the site of pleural intervention within 12 months from randomisation, assessed in the intention-to-treat population. This trial is registered with ISRCTN, number ISRCTN72767336. FINDINGS: Between Dec 23, 2011, and Aug 4, 2014, we randomised 203 patients to receive immediate radiotherapy (n=102) or deferred radiotherapy (n=101). The patients were well matched at baseline. No significant difference was seen in PTM incidence in the immediate and deferred radiotherapy groups (nine [9%] vs 16 [16%]; odds ratio 0·51 [95% CI 0·19-1·32]; p=0·14). The only serious adverse event related to a PTM or radiotherapy was development of a painful PTM within the radiotherapy field that required hospital admission for symptom control in one patient who received immediate radiotherapy. Common adverse events of immediate radiotherapy were skin toxicity (grade 1 in 50 [54%] and grade 2 in four [4%] of 92 patients vs grade 1 in three [60%] and grade 2 in two [40%] of five patients in the deferred radiotherapy group who received radiotherapy for a PTM) and tiredness or lethargy (36 [39%] in the immediate radiotherapy group vs two [40%] in the deferred radiotherapy group) within 3 months of receiving radiotherapy. INTERPRETATION: Routine use of prophylactic radiotherapy in all patients with mesothelioma after large-bore thoracic interventions is not justified. FUNDING: Research for Patient Benefit Programme from the UK National Institute for Health Research.

Incidence of CT Contrast Agent-Induced Nephropathy: Toward a More Accurate Estimation.

OBJECTIVE: Acute kidney injury is common among hospitalized patients and likely leads to inflated reports of the incidence of CT contrast agent-induced nephropathy as a cause of acute kidney injury. For a more accurate estimation, we compared the incidence of acute kidney injury immediately after contrast agent administration and a few days afterward in the same population. We also controlled for a creatinine level increase starting before and continuing after CT, which may be incorrectly associated with the scan itself. MATERIALS AND METHODS: After excluding patients undergoing dialysis, we included all adults who underwent CT from January 2006 through May 2013 in our health region. The incidence of acute kidney injury (Acute Kidney Injury Network stages) and dialysis after acute kidney injury were assessed in the immediate period (24-48 hours) and in a delayed period (72-96 hours) after the scan. New acute kidney injury in either period occurred if the creatinine level had increased at a greater rate than that in a preceding 24-hour interval. The incidence of acute kidney injury and dialysis after acute kidney injury attributable to CT were calculated by subtracting the delayed incidence from the immediate incidence. RESULTS: Incidences of acute kidney injury and dialysis after acute kidney injury attributable to contrast-enhanced CT were statistically insignificant across glomerular filtration rate (GFR) subgroups. Acute kidney injury incidences (Acute Kidney Injury Network stage I or worse) were 0.5% (95% CI, -0.4% to 1.4%) for GFR greater than 60 mL/min/1.73 m(2), 2.4% (95% CI, -0.7% to 5.6%) for GFR 30-59 mL/min/1.73 m(2), -4.3% (95% CI, -19.8% to 11.3%) for GFR 15-29 mL/min/1.73 m(2), and 0% (95% CI, -24.5% to 24.5%) for GFR less than 15 mL/min/1.73 m(2). CONCLUSION: There appears to be a minimal risk of CT contrast agent-induced nephropathy at mild to moderate levels of renal dysfunction.

Validity of cardiovascular risk prediction models in kidney transplant recipients.

BACKGROUND: Predicting cardiovascular risk is of great interest in renal transplant recipients since cardiovascular disease is the leading cause of mortality. OBJECTIVE: To conduct a systematic review to assess the validity of cardiovascular risk prediction models in this population. METHODS: Five databases were searched (MEDLINE, EMBASE, SCOPUS, CINAHL, and Web of Science) and cohort studies with at least one year of follow-up were included. Variables that described population characteristics, study design, and prognostic performance were extracted. The Quality in Prognostic Studies (QUIPS) tool was used to evaluate bias. RESULTS: Seven studies met the criteria for inclusion, of which, five investigated the Framingham risk score and three used a transplant-specific model. Sample sizes ranged from 344 to 23,575, and three studies lacked sufficient event rates to confidently reach conclusion. Four studies reported discrimination (as measured by c-statistic), which ranged from 0.701 to 0.75, while only one risk model was both internally and externally validated. CONCLUSION: The Framingham has underestimated cardiovascular events in renal transplant recipients, but these studies have not been robust. A risk prediction model has been externally validated at least on one occasion, but comprehensive validation in multiple cohorts and impact analysis are recommended before widespread clinical application is advocated.