Targeted CQA analytical control strategy for commercial antibody products: Replacing ion-exchange chromatography methods for charge heterogeneity with multi-attribute monitoring.

Peptide mapping with mass spectrometry (MS) is an important tool for protein characterization in the biopharmaceutical industry. Historically, peptide mapping monitors post-translational modifications (PTMs) of protein products and process intermediates during development. Multi-attribute monitoring (MAM) methods have been used previously in commercial release and stability testing panels to ensure control of selected critical quality attributes (CQAs). Our goal is to use MAM methods as part of an overall analytical testing strategy specifically focused on CQAs, while removing or replacing historical separation methods that do not effectively distinguish CQAs from non-CQAs due to co-elution. For example, in this study, we developed a strategy to replace a profile-based ion-exchange chromatography (IEC) method using a MAM method in combination with traditional purity methods to ensure control of charge variant CQAs for a commercial antibody (mAb) drug product (DP). To support this change in commercial testing strategy, the charge variant CQAs were identified and characterized during development by high-resolution LC-MS and LC-MS/MS. The charge variant CQAs included PTMs, high molecular weight species, and low molecular weight species. Thus, removal of the IEC method from the DP specification was achieved using a validated LC-MS MAM method on a QDa system to directly measure the charge variant PTM CQAs in combination with size exclusion chromatography (SE-HPLC) and capillary electrophoresis (CE-SDS) to measure the non-PTM charge variant CQAs. Bridging data between the MAM, IEC, and SE-HPLC methods were included in the commercial marketing application to justify removing IEC from the DP specification. We have also used this MAM method as a test for identity to reduce the number of QC assays. This strategy has received approvals from several health authorities.

Brachial Gunshot Wounds: Injury Patterns and Considerations for Managing the Abnormal Neurological Examination.

BACKGROUND: Nerve injuries from gunshot wounds (GSWs) to the upper arm can cause significant morbidity and loss of function. However, indications for surgical exploration and nerve reconstruction remain unclear as both low- and high-grade injuries can present with an abnormal neurological examination. METHODS: Adult patients presenting with a history of isolated GSW to the upper arm between 2010 and 2019 at a single urban level 1 trauma center were screened for inclusion in this retrospective study. Patient demographics, neurological examination findings, concurrent injuries, and intraoperative findings were gathered. Bivariate analysis was performed to characterize factors associated with nerve injuries. RESULTS: There were 139 adult patients with isolated brachial GSWs, and 49 patients (35%) presented with an abnormal neurological examination and significantly associated with concurrent humerus fractures (39% vs 21%, P = .026) and brachial artery injuries (31% vs 2%, P < .001). Thirty of these 49 patients were operatively explored. Fifteen patients were found to have observed nerve injuries during operative exploration including 8 patients with nerve transections. The radial nerve was the most commonly transected nerve (6), and among the 16 contused nerves, the median (8) was most common. CONCLUSION: Nerve injury from upper arm GSWs is common with directly traumatized nerves confirmed in at least 39% and nerve transection in at least 16% of patients with an abnormal neurological examination. Timely referral to a hand and/or peripheral nerve surgeon for close clinical follow-up, appropriate diagnosis, and any necessary surgical reconstruction with nerve grafts, tendon transfers, and nerve transfers is recommended.

Reduced Access to Acute Hand Care and Potential Role of Telemedicine in Tennessee During the COVID Pandemic.

INTRODUCTION: Previous studies have identified that there is limited, although expanding, access to acute hand care in Tennessee. Because of the rapid changes that occurred in health delivery and access during the coronavirus disease pandemic, we reassessed access to acute hand care, with particular interest in the utilization of telemedicine to assess if this increased access. METHOD: We surveyed Tennessee hospitals listed by the Tennessee Hospital Association on their management of hand trauma and availability of telemedicine programs. Census data including population demographics such as race, age, income, and county size were merged with the survey data. Descriptive analysis was performed comparing the 2021 cohort with the historic 2018 cohort and between counties that had hand care versus counties that had no hand care. RESULT: Survey response rate was 71.4% (n = 80 of 112). Telemedicine was used in 80% of the hospitals for other specialties but was not used for hand care. Overall, counties that offered hand trauma care reduced from 60% to 26% from 2018 to 2021 ( P < 0.001). This change was associated with a significant reduction of acute hand care among counties that were classified micropolitan (from 56.3% to 6.7%, P < 0.01). Percentage of hand specialists on staff and 24/7 specialists availability remained low and were similar to the availability in 2018. CONCLUSIONS: There was a decrease of acute hand care access in Tennessee during the coronavirus disease pandemic despite widespread utilization of telemedicine for other specialty consults. Expansion of telemedicine in acute hand care, targeted to micropolitan areas, may help to reduce variability in access to care.

How Person-Centred Is Cardiac Rehabilitation in England? Using Bourdieu to Explore Socio-Cultural Influences and Personalisation.

The National Health Service (NHS) cardiac rehabilitation patient care pathway has remained largely unchanged for many years despite, on average, half of all eligible patients declining to engage. To investigate reasons for non-engagement, we explored the experiences of ten cardiac patients who participated in cardiac rehabilitation, dropped out, or declined, as well as experiences of seven people deemed significant others by participants. Our ethnographic study involved participant observations, repeat in-depth semi-structured interviews, and reflexive journaling. Reflexive thematic analysis was conducted, focusing on participants' lived experiences. Utilising Bourdieusian concepts of habitus, capital, and field, this article highlights how personal biography, material conditions, and dispositional inclinations combine to make cardiac health care decision-making individual and complex. Despite this, health professionals were not always attuned to specific circumstances arising from differences in patients' experiences and lifeworlds. By considering service improvement recommendations that acknowledge socio-cultural influences, cardiac rehabilitation can work towards providing patients and their significant others with more appropriate, personalised, and person-centred support.

Weight Bias in Reproductive Medicine: A Curiously Unexplored Frontier.

Obesity has been associated with a multitude of medical comorbidities, infertility, and adverse obstetric outcomes. Weight stigma and weight bias pervade not only the medical field but also education, employment, and activities of daily living. The experience of weight stigma has been shown to adversely impact not only the mental health of individuals with overweight or obesity but also worsen obesogenic behaviors, and medical comorbidities. This review frames the rise of weight stigma and weight bias within the context of the "obesity epidemic" and explores its associations with infertility and decreased access to health care and its subsequent impact on the lives of individuals. Furthermore, it explores the concepts of intrinsic and extrinsic weight stigma/bias and highlights the need for further examination and research into the impact of these factors on access to reproductive medicine and subsequent outcomes.

Overnight Melatonin Concentration and Sleep Quality Are Associated with the Clinical Features of Polycystic Ovary Syndrome.

Circulating melatonin is elevated in women with polycystic ovary syndrome (PCOS); whether circadian disruptions coincide with sleep disturbances in women with PCOS or their symptom severity is unclear. The objective of this observational pilot study was to determine whether altered patterns of melatonin excretion are associated with reduced sleep quality in women with versus without PCOS. Participants underwent a clinical assessment, transvaginal ultrasound, and reproductive hormone testing. Morning and evening urine samples were assayed for urinary 6-sulfatoxymelatonin (MEL) as a proxy for melatonin production. The night (morning MEL)-to-day (evening MEL) ratio, or N:D ratio, was determined to approximate the rhythm of MEL production. Sleep quality and duration were assessed using the Pittsburgh Sleep Quality Index (PSQI) and wrist actigraphy. No differences were detected in overnight MEL, daytime MEL, or the N:D ratio in participants with PCOS versus controls. The PCOS group experienced reduced weekend sleep efficiency vs. controls (81% vs. 88% p < 0.05). The number of follicles per ovary (FNPO) was positively associated with overnight MEL (r = 0.359, p < 0.05). Weekend sleep time and overnight MEL concentrations were dependent on PCOS status. Therefore, diagnostic features of PCOS were associated with MEL production and sleep disturbances, suggesting that women with a more severe clinical presentation of PCOS may be more likely to experience altered MEL production or sleep disturbances.

High-Throughput Expression and Purification of Human Solute Carriers for Structural and Biochemical Studies.

Solute carriers (SLCs) are membrane transporters that import and export a range of endogenous and exogenous substrates, including ions, nutrients, metabolites, neurotransmitters, and pharmaceuticals. Despite having emerged as attractive therapeutic targets and markers of disease, this group of proteins is still relatively underdrugged by current pharmaceuticals. Drug discovery projects for these transporters are impeded by limited structural, functional, and physiological knowledge, ultimately due to the difficulties in the expression and purification of this class of membrane-embedded proteins. Here, we demonstrate methods to obtain high-purity, milligram quantities of human SLC transporter proteins using codon-optimized gene sequences. In conjunction with a systematic exploration of construct design and high-throughput expression, these protocols ensure the preservation of the structural integrity and biochemical activity of the target proteins. We also highlight critical steps in the eukaryotic cell expression, affinity purification, and size-exclusion chromatography of these proteins. Ultimately, this workflow yields pure, functionally active, and stable protein preparations suitable for high-resolution structure determination, transport studies, small-molecule engagement assays, and high-throughput in vitro screening.

Association between sex steroid hormones and subsequent hyperglycemia during pregnancy.

Objective: Sex steroid hormones may play a role in insulin resistance and glucose dysregulation. However, evidence regarding associations between early-pregnancy sex steroid hormones and hyperglycemia during pregnancy is limited. The primary objective of this study was to assess the relationships between first trimester sex steroid hormones and the subsequent development of hyperglycemia during pregnancy; with secondary evaluation of sex steroid hormones levels in mid-late pregnancy, concurrent with and subsequent to diagnosis of gestational diabetes. Methods: Retrospective analysis of a prospective pregnancy cohort study was conducted. Medically low-risk participants with no known major endocrine disorders were recruited in the first trimester of pregnancy (n=319). Sex steroid hormones in each trimester, including total testosterone, free testosterone, estrone, estradiol, and estriol, were assessed using high-performance liquid chromatography and tandem mass spectrometry. Glucose levels of the 1-hour oral glucose tolerance test and gestational diabetes diagnosis were abstracted from medical records. Multivariable linear regression models were fitted to assess the associations of individual first trimester sex steroids and glucose levels. Results: In adjusted models, first trimester total testosterone (ß=5.24, 95% CI: 0.01, 10.46, p=0.05) and free testosterone (ß=5.98, 95% CI: 0.97, 10.98, p=0.02) were positively associated with subsequent glucose concentrations and gestational diabetes diagnosis (total testosterone: OR=3.63, 95% CI: 1.50, 8.78; free testosterone: OR=3.69; 95% CI: 1.56, 8.73). First trimester estrone was also positively associated with gestational diabetes (OR=3.66, 95% CI: 1.56, 8.55). In mid-late pregnancy, pregnant people with gestational diabetes had lower total testosterone levels (ß=-0.19, 95% CI: -0.36, -0.02) after adjustment for first trimester total testosterone. Conclusion: Early-pregnancy sex steroid hormones, including total testosterone, free testosterone, and estrone, were positively associated with glucose levels and gestational diabetes in mid-late pregnancy. These hormones may serve as early predictors of gestational diabetes in combination with other risk factors.

Nerve blocks for occipital headaches: A systematic review and meta-analysis.

Migraine surgeons have identified six "trigger sites" where cranial nerve compression may trigger a migraine. This study investigates the change in headache severity and frequency following nerve block of the occipital trigger site. This PRISMA-compliant systematic review of five databases searched from database inception through May 2020 is registered under the PROSPERO ID: CRD42020199369. Only randomized controlled trials utilizing injection treatments for headaches with pain or tenderness in the occipital scalp were included. Pain severity was scored from 0 to 10. Headache frequency was reported as days per week. Included were 12 RCTs treating 586 patients of mean ages ranging from 33.7 to 55.8 years. Meta-analyses of pain severity comparing nerve blocks to baseline showed statistically significant reductions of 2.88 points at 5 to 20 min, 3.74 points at 1 to 6 weeks, and 1.07 points at 12 to 24 weeks. Meta-analyses of pain severity of nerve blocks compared with treatment groups of neurolysis, pulsed radiofrequency, and botulinum toxin type A showed similar headache pain severity at 1 to 2 weeks, and inferior improvements compared with the treatment groups after 2 weeks. Meta-analyses of headache frequency showed statistically significant reductions at 1 to 6-week follow-ups as compared with baseline and at 1 to 6 weeks as compared with inactive control injections. The severity and frequency of occipital headaches are reduced following occipital nerve blocks. This improvement is used to predict the success of migraine surgery. Future research should investigate spinous process injections with longer follow-up.

Implantable, Bioresorbable Radio Frequency Resonant Circuits for Magnetic Resonance Imaging.

Magnetic resonance imaging (MRI) is widely used in clinical care and medical research. The signal-to-noise ratio (SNR) in the measurement affects parameters that determine the diagnostic value of the image, such as the spatial resolution, contrast, and scan time. Surgically implanted radiofrequency coils can increase SNR of subsequent MRI studies of adjacent tissues. The resulting benefits in SNR are, however, balanced by significant risks associated with surgically removing these coils or with leaving them in place permanently. As an alternative, here the authors report classes of implantable inductor-capacitor circuits made entirely of bioresorbable organic and inorganic materials. Engineering choices for the designs of an inductor and a capacitor provide the ability to select the resonant frequency of the devices to meet MRI specifications (e.g., 200 MHz at 4.7 T MRI). Such devices enhance the SNR and improve the associated imaging capabilities. These simple, small bioelectronic systems function over clinically relevant time frames (up to 1 month) at physiological conditions and then disappear completely by natural mechanisms of bioresorption, thereby eliminating the need for surgical extraction. Imaging demonstrations in a nerve phantom and a human cadaver suggest that this technology has broad potential for post-surgical monitoring/evaluation of recovery processes.

Mechanism matters: A 10-year experience of ballistic injuries of the upper extremity.

INTRODUCTION: Upper Extremity gunshot wounds represent a significant strain on community and hospital resources, and reports of their epidemiology are varied. We hypothesized that demographic and socioeconomic variables would be associated with variable injury patterns and management, and that two distinct populations would be affected by upper extremity ballistic injury based on violent versus accidental, self-inflicted mechanism. MATERIALS & METHODS: Retrospective review of all adult patients sustaining ballistic injury to the upper extremity at a single urban Level I trauma center over 10 years (n = 797). Demographic, injury pattern, treatment, and outcomes data were collected. Comparisons between groups were conducted with unpaired t-tests and chi-square testing where appropriate. RESULTS: Most patients were male (89.1%) and mean age was 30.1 years (18-83). Violence accounted for 89.1% of injuries. Black individuals were disproportionately affected at 87% of patients. Shoulder injuries were most common (34%), and wrist least common (7%). Demographics and injury pattern varied significantly between patients sustaining violent injury and those with self-inflicted mechanisms. Patients sustaining violent injury were most often young, Black men more likely to be injured proximally, whereas patients with self-inflicted injuries were more likely to be older, Caucasian men with more comorbidities injured distally. Cumulatively, 35.3% of patients required operative intervention. Distal injuries were more likely operative. The most commonly injured structure across all levels was bone (53%), and 54.3% of fractures required operation. Median follow-up was 24.5 months. Complication rate was 13.6%. CONCLUSIONS: Gunshot wounds of the upper extremity create complex patterns of injury which vary based on level of injury and mechanism. Violent and self-inflicted injuries occur in dissimilar populations and result in distinctive injury patterns.

Outcomes of Surgical Treatment of Migraines: A Systematic Review & Meta-Analysis.

Background: Migraine surgery at 1 of 6 identified "trigger sites" of a target cranial sensory nerve has rapidly grown in popularity since 2000. This study summarizes the effect of migraine surgery on headache severity, headache frequency, and the migraine headache index score which is derived by multiplying migraine severity, frequency, and duration. Materials and Methods: This is a PRISMA-compliant systematic review of 5 databases searched from inception through May 2020 and is registered under the PROSPERO ID: CRD42020197085. Clinical trials treating headaches with surgery were included. Risk of bias was assessed in randomized controlled trials. Meta-analyses were performed on outcomes using a random effects model to determine the pooled mean change from baseline and when possible, to compare treatment to control. Results: 18 studies met criteria including 6 randomized controlled trials, 1 controlled clinical trial, and 11 uncontrolled clinical trials treated 1143 patients with pathologies including migraine, occipital migraine, frontal migraine, occipital nerve triggered headache, frontal headache, occipital neuralgia, and cervicogenic headache. Migraine surgery reduced headache frequency at 1 year postoperative by 13.0 days per month as compared to baseline (I2 = 0%), reduced headache severity at 8 weeks to 5 years postoperative by 4.16 points on a 0 to 10 scale as compared to baseline (I2 = 53%), and reduced migraine headache index at 1 to 5 years postoperative by 83.1 points as compared to baseline (I2 = 2%). These meta-analyses are limited by a small number of studies that could be analyzed, including studies with high risk of bias. Conclusion: Migraine surgery provided a clinically and statistically significant reduction in headache frequency, severity, and migraine headache index scores. Additional studies, including randomized controlled trials with low risk-of-bias should be performed to improve the precision of the outcome improvements.

Historique: Le traitement de la migraine à l'une des six « zones gâchettes ¼ établies d'un nerf crânien sensoriel cible ont rapidement gagné en popularité depuis 2000. La présente étude résume l'effet du traitement chirurgical de la migraine sur la gravité et la fréquence des céphalées et sur le score de migraine obtenu par la multiplication de la gravité, de la fréquence et de la durée des migraines. Matériel et méthodologie: La présente analyse systématique de cinq bases de données fouillées depuis leur création jusqu'à mai 2020 respecte la liste PRISMA et est enregistrée sous le numéro d'identification CRD42020197085 de PROSPERO. Les chercheurs ont retenu les études cliniques sur le traitement des céphalées par des interventions chirurgicales. Ils ont évalué le risque de biais des études aléatoires et contrôlées. Ils ont également effectué des méta-analyses des résultats au moyen d'un modèle à effets aléatoires pour déterminer le changement moyen regroupé par rapport à l'état de référence et, dans la mesure du possible, pour comparer des sujets traités à des sujets témoins. Résultats: Au total, 18 études respectaient les critères, y compris six études aléatoires et contrôlées, une étude clinique contrôlée, et 11 études non contrôlées auprès de 1 143 patients ayant des pathologies incluant la migraine, la migraine occipitale, la migraine frontale, la céphalée occipitale, la céphalée frontale, la névralgie occipitale et la céphalée cervicogénique. Par rapport à l'état de départ, le traitement chirurgical de la migraine avait réduit la fréquence des céphalées de 13,0 jours par mois (I2 = 0%) un an après l'opération, la gravité des céphalées de 4,16 points sur une échelle de 0 à 10 de huit semaines à cinq ans après l'opération (I2 = 53%) et le score de migraine de 83,1 points de un à cinq ans après l'opération (I2 = 2%). Ces méta-analyses sont limitées par le petit nombre d'études pouvant être analysées, y compris des études comportant de forts risques de biais. Conclusion: Le traitement chirurgical de la migraine assure une diminution cliniquement et statistiquement significative de la fréquence et de la gravité des céphalées, ainsi que des scores de migraine. D'autres études, y compris des études aléatoires et contrôlées comportant un faible risque de biais, devront être exécutées pour mieux préciser les améliorations aux résultats cliniques.

Structure and Dynamics of Three Escherichia coli NfsB Nitro-Reductase Mutants Selected for Enhanced Activity with the Cancer Prodrug CB1954.

Escherichia coli NfsB has been studied extensively for its potential for cancer gene therapy by reducing the prodrug CB1954 to a cytotoxic derivative. We have previously made several mutants with enhanced activity for the prodrug and characterised their activity in vitro and in vivo. Here, we determine the X-ray structure of our most active triple and double mutants to date, T41Q/N71S/F124T and T41L/N71S. The two mutant proteins have lower redox potentials than wild-type NfsB, and the mutations have lowered activity with NADH so that, in contrast to the wild-type enzyme, the reduction of the enzyme by NADH, rather than the reaction with CB1954, has a slower maximum rate. The structure of the triple mutant shows the interaction between Q41 and T124, explaining the synergy between these two mutations. Based on these structures, we selected mutants with even higher activity. The most active one contains T41Q/N71S/F124T/M127V, in which the additional M127V mutation enlarges a small channel to the active site. Molecular dynamics simulations show that the mutations or reduction of the FMN cofactors of the protein has little effect on its dynamics and that the largest backbone fluctuations occur at residues that flank the active site, contributing towards its broad substrate range.

Antibiotic Prophylaxis and Infectious Complications in Isolated Gunshot Wounds to the Upper Extremity.

BACKGROUND: Prophylactic antibiotics are variably prescribed after isolated upper extremity gunshot wounds (UE GSWs). The risk of infection and factors influencing prescribing practice remain poorly understood, and clinical practice guidelines are lacking. METHODS: Adults with isolated UE GSWs over a 10-year period were included. Medical records were reviewed for demographic and injury variables, comorbidities, surgical treatments, antibiotic administration, infectious complications, and follow-up duration. Infection rate was calculated. Bivariate and multivariable linear regression analyses were used to identify patient-related and injury-related factors predictive of prophylactic antibiotic prescription. RESULTS: A total of 281 patients were eligible for inclusion. Prophylactic antibiotics were prescribed at discharge for 111 patients (40%). Multivariable analysis revealed that patients with more distal injuries and ballistic fractures were significantly more likely to receive prophylactic antibiotics. Of patients with at least 30-day postinjury follow-up, 6% developed infections. CONCLUSION: Prophylactic antibiotic administration after UE GSWs was inconsistent but more common in patients with ballistic fractures and injuries in the hand. The overall incidence of infection was found to lie between 3% and 6%. The rate of infection in the antibiotic prophylaxis (2%-6%) group was similar to that in the no-antibiotic (5%-7%) group, suggesting that antibiotic prophylaxis may not have a large impact on infectious risk. However, because this study is nonrandomized, and because this study is underpowered for multivariable modeling of infectious risk, it remains possible that subgroups of this population may still benefit from antibiotic prophylaxis.

Beyond the Cubital Tunnel: Use of Adjunctive Procedures in the Management of Cubital Tunnel Syndrome.

BACKGROUND: Our management of cubital tunnel syndrome has expanded to involve multiple adjunctive procedures, including supercharged end-to-side anterior interosseous to ulnar nerve transfer, cross-palm nerve grafts from the median to ulnar nerve, and profundus tenodesis. We also perform intraoperative brief electrical stimulation in patients with severe disease. The aims of this study were to evaluate the impact of adjunctive procedures and electrical stimulation on patient outcomes. METHODS: We performed a retrospective review of 136 patients with cubital tunnel syndrome who underwent operative management from 2013 to 2018. A total of 38 patients underwent adjunctive procedure(s), and 33 received electrical stimulation. A historical cohort of patients who underwent cubital tunnel surgery from 2009 to 2011 (n = 87) was used to evaluate the impact of adjunctive procedures. Study outcomes were postoperative improvements in Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire scores, pinch strength, and patient-reported pain and quality of life. RESULTS: In propensity score-matched samples, patients who underwent adjunctive procedures had an 11.3-point greater improvement in DASH scores than their matched controls (P = .0342). In addition, patients who received electrical stimulation had significantly improved DASH scores relative to baseline (11.7-point improvement, P < .0001), whereas their control group did not. However, when compared between treatment arms, there were no significant differences for any study outcome. CONCLUSIONS: Patients who underwent adjunctive procedures experienced greater improvement in postoperative DASH scores than their matched pairs. Additional studies are needed to evaluate the effects of brief electrical stimulation in compression neuropathy.

Can Diffusion Tensor Imaging Apparent Diffusion Coefficient Diagnose Carpal Tunnel Syndrome? A Systematic Review and Meta-Analysis.

Magnetic resonance diffusion tensor imaging (DTI) can detect microstructural changes in peripheral nerves. Studies have reported that the median nerve apparent diffusion coefficient (ADC), a quantification of water molecule diffusion direction, is sensitive in diagnosing carpal tunnel syndrome (CTS). Five databases were searched for studies using ADC to investigate CTS. Apparent diffusion coefficient (measured in mm2/s) were pooled in random-effects meta-analyses. Twenty-two studies met criteria yielding 592 patients with CTS and 414 controls. Median nerve ADC were measured at the level of the distal radioulnar joint (CTS ADC: 1.11, 95% CI: 1.07-1.15, I2 = 54%; control ADC: 1.04, 95% CI: 1.01-1.07, I2 = 57%), pisiform (CTS ADC: 1.39, 95% CI: 1.37-1.42, I2 = 0%; control ADC: 1.27, 95% CI: 1.23-1.31, I2 = 59%), hamate (CTS ADC: 1.40, 95% CI: 1.36-1.43, I2 = 58%; control ADC: 1.27, 95% CI: 1.25-1.28, I2 = 47%), and as an combination of several measurements (CTS ADC: 1.40, 95% CI: 1.37-1.47, I2 = 100%; control ADC: 1.39, 95% CI: 1.24-1.53, I2 = 100%). Median nerve ADC is decreased in individuals with CTS compared to controls at the levels of the hamate and pisiform. ADC cut-offs to diagnose CTS should be established according to these anatomic levels and can be improved through additional studies that include use of a wrist coil.

Nationwide Clinical Practice Patterns of Anesthesiology Critical Care Physicians: A Survey to Members of the Society of Critical Care Anesthesiologists.

BACKGROUND: Despite the growing contributions of critical care anesthesiologists to clinical practice, research, and administrative leadership of intensive care units (ICUs), relatively little is known about the subspecialty-specific clinical practice environment. An understanding of contemporary clinical practice is essential to recognize the opportunities and challenges facing critical care anesthesia, optimize staffing patterns, assess sustainability and satisfaction, and strategically plan for future activity, scope, and training. This study surveyed intensivists who are members of the Society of Critical Care Anesthesiologists (SOCCA) to evaluate practice patterns of critical care anesthesiologists, including compensation, types of ICUs covered, models of overnight ICU coverage, and relationships between these factors. We hypothesized that variability in compensation and practice patterns would be observed between individuals. METHODS: Board-certified critical care anesthesiologists practicing in the United States were identified using the SOCCA membership distribution list and invited to take a voluntary online survey between May and June 2021. Multiple-choice questions with both single- and multiple-select options were used for answers with categorical data, and adaptive questioning was used to clarify stem-based responses. Respondents were asked to describe practice patterns at their respective institutions and provide information about their demographics, salaries, effort in ICUs, as well as other activities. RESULTS: A total of 490 participants were invited to take this survey, and 157 (response rate 32%) surveys were completed and analyzed. The majority of respondents were White (73%), male (69%), and younger than 50 years of age (82%). The cardiothoracic/cardiovascular ICU was the most common practice setting, with 69.5% of respondents reporting time working in this unit. Significant variability was observed in ICU practice patterns. Respondents reported spending an equal proportion of their time in clinical practice in the operating rooms and ICUs (median, 40%; interquartile range [IQR], 20%-50%), whereas a smaller proportion-primarily those who completed their training before 2009-reported administrative or research activities. Female respondents reported salaries that were $36,739 less than male respondents; however, this difference was not statistically different, and after adjusting for age and practice type, these differences were less pronounced (-$27,479.79; 95% confidence interval [CI], -$57,232.61 to $2273.03; P = .07). CONCLUSIONS: These survey data provide a current snapshot of anesthesiology critical care clinical practice patterns in the United States. Our findings may inform decision-making around the initiation and expansion of critical care services and optimal staffing patterns, as well as provide a basis for further work that focuses on intensivist satisfaction and burnout.

Activating the 'peerness' of youth leaders in a community sports programme through techne and phronesis.

Peer-to-peer approaches engage groups of people considered to share one or more characteristics that identify them as peers and draw on rationales of credibility, identification and role modelling in peer-to-peer interactions. Despite the popularity of the approach, the ways in which the peer leadership component specifically contributes to health promotion is not thoroughly understood. We suggest that a first step for making use of peer leader characteristics is to make explicit what the peer leadership component is expected to bring to a programme. To approach such an understanding, we investigated how peer leaders can be supported in activating their 'peerness' in health promotion programmes, using as a case the peer leader education of a youth-led, peer-to-peer community sports programme, implemented by the non-profit street sports organization, GAME. We analysed the peer leader training programme's learning objectives and field notes from observations of the training programme. The empirical material was analysed using an abductive approach by drawing upon contemporary interpretations of two forms of knowledge originally proposed by Aristotle. In so doing, this article explores how the development of techne (practical knowledge) and phronesis (practical wisdom) was supported in a peer leader training programme for young people. Findings suggest that supporting the development of both these types of knowledge can strengthen programme planners' attention to the contribution of peers. Concurrently, an emphasis on promoting phronesis in peer leader training can support and encourage peer leaders in activating their 'peerness' in peer-to-peer health promotion programmes.

Peer-to-peer approaches are commonly used in the health promotion. Peer-led programmes engage groups of people considered to share one or more characteristics that identify them as peers. Peer leaders are suggested to be credible sources of information and provide identification and role modelling to their peers. However, despite the popularity of the approach, the ways in which peer leaders specifically contribute to health promotion are not thoroughly understood. It is thus unclear how the 'peerness' of peer leaders is activated in health promotion programmes. In this study, we investigated how peer leaders can be supported in activating their 'peerness' during peer-led activities. To do so, we observed and analysed the peer leader training programme of a youth-led community sport programme, implemented by the non-profit organization, GAME. As a theoretical framework, we employed two forms of knowledge originally proposed by Aristotle; namely, techne (practical knowledge) and phronesis (practical wisdom). Our results suggest that supporting the development of both these types of knowledge can strengthen programme planners' attention to the contribution of peers. Concurrently, an emphasis on promoting phronesis in peer leader training can support and encourage peer leaders in activating their 'peerness' in peer-to-peer health promotion programmes.

Postamputation Residual Limb Pain Severity and Prevalence: A Systematic Review and Meta-Analysis.

Background: Individuals with an extremity amputation are predisposed to persistent pain that reduces their quality of life. Residual limb pain is defined as pain that is felt in the limb after amputation. Methods: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review of 5 databases from inception to June 2020 was performed and is registered under the PROSPERO ID: CRD42020199297. Included studies were clinical trials with residual limb pain assessed at a minimum follow-up of 1 week. Meta-analyses of residual limb pain prevalence and severity were performed with subgroups of extremity and amputation etiology. Results: Twenty clinical trials met criteria and reported on a total of 1347 patients. Mean patient ages ranged from 38 to 77. Residual limb pain prevalence at 1 week, 1 month, 3 months, 6 months, 1 year, and 2 years, respectively, was 50%, 11%, 23%, 27%, 22%, and 24%. Mean residual limb pain severity at the 6 months or longer follow-up was 4.19 out of 10 for cancer amputations, 2.70 for traumatic amputations, 0.47 for vasculopathy amputations, 1.01 for lower extremity amputations, and 3.56 for upper extremity amputations. Conclusions: Residual limb pain severity varies according to the etiology of amputation and is more common after upper extremity amputation than lower extremity amputations. The most severe pain is reported by patients undergoing amputations due to cancer, followed by traumatic amputations, while vascular amputation patients report lower pain severity. Promising methods of reducing long-term pain are preoperative pain control, nerve or epidural blocks, use of memantine, calcitonin-containing blocks, and prophylactic nerve coaptations.

Contexte: Les personnes subissant une amputation d'un membre sont prédisposées à des douleurs persistantes réduisant leur qualité de vie. La douleur du membre résiduel est définie comme étant la douleur ressentie dans le membre après l'amputation. Méthodes: Une revue systématique conforme à PRISMA de 5 bases de données depuis leur création jusqu'en juin 2020 a été effectuée et enregistrée sous l'ID PROSPERO: CRD42020199297. Les études incluses étaient des essais cliniques avec douleur du membre résiduel évaluée à un suivi minimum de 1 semaine. Des méta-analyses sur la prévalence et la sévérité de la douleur du membre résiduel ont été réalisées avec des sous-groupes en fonction du membre et de la cause de l'amputation. Résultats: 20 essais cliniques satisfaisaient les critères et portaient sur un total de 1347 patients. Les âges moyens des patients étaient compris entre 38 et 77 ans. La prévalence de la douleur du membre résiduel à 1 semaine, 1 mois, 3 mois, 6 mois, 1 an et 2 ans était, respectivement, de 50%, 11%, 23%, 27%, 22%, et 24%. La sévérité moyenne de la douleur du membre résiduel aux suivis de 6 mois ou plus a été de 4,19 sur 10 pour les amputations pour cancer, 2,70 pour les amputations post traumatisme, 0,47 pour les amputations liées à une vasculopathie, 1,01 pour les amputations du membre inférieur et 3,56 pour les amputations du membre supérieur. Conclusions: La sévérité de la douleur du membre résiduel varie en fonction du motif de l'amputation, et elle est plus fréquente après une amputation du membre supérieur qu'après des amputations du membre inférieur. La douleur la plus sévère a été décrite par des patients subissant une amputation à cause d'un cancer, suivie des amputations traumatiques, alors que les patients ayant subi une amputation pour cause vasculaire signalent une sévérité plus faible. Des méthodes prometteuses de réduction de la douleur à long terme sont le contrôle préopératoire de la douleur, les blocs nerveux et épiduraux, l'utilisation de la mémantine, de blocs contenant de la calcitonine et la coaptation prophylactique des nerfs.