Mitigating emotional responses to stressors: coping strategies, modifiers and support.

OBJECTIVE: The stressful nature of the intensive care unit (ICU) environment is increasingly well characterised. The aim of this paper was to explore modifiers, coping strategies and support pathways identified by experienced Intensivists, in response to these stressors. METHOD: Prospective qualitative study employing interviews with Intensivists in two countries. Participants were asked how they mitigated their emotional responses to the stressors of the ICU. Audio-recordings were transcribed and analysed by all researchers who agreed upon emerging themes and subthemes. RESULTS: A wide range of strategies were reported. Although several participants had sought professional help and all supported its utility, few disclosed accessing such help to others indicating stigma. Many felt a sense of responsibility for the well-being of other staff but identified barriers that suggest alternate support pathways are required. Further implications of these findings to training considerations are described. CONCLUSIONS: Several approaches were described as regularly employed by Intensivists to mitigate ICU environmental stressors. Intensivists perceive themselves to have limited training to provide support to others; they also perceive stigma in seeking professional help.

Behavioural responses of Intensivists to stressors in Intensive Care.

BACKGROUND: The hospital intensive care unit (ICU) environment encompasses sick patients who present for care in health crisis. Healthcare in this setting is complex, often involving the co-ordination of multiple professional teams, all under significant time pressures. The sequelae for staff interacting in this dynamic and often volatile setting are variable, depending upon their coping skillset and their familiarity with the stressors. AIMS: The primary aim of this study was to describe and in doing so, normalize the behavioural responses expressed by ICU doctors (Intensivists) in response to stressful workplace events. The secondary aim was to identify those responses that contributed to resilience. METHODS: A prospective qualitative study of senior Intensivists using a semi-scripted iterative interview. Data were transcribed and thematically analysed with verbatim quotations selected to support coding choices. RESULTS: Nineteen experienced Intensivists from three sites in Australia and Israel participated. Clinicians described conscious, physiological and professional responses to stressors, including sense-making and taking time to process information with appropriate support. Two of the most important mitigation processes revealed were the use of reflective learning and preventative practice changes to prevent future errors. These were overlaid with the importance of disclosure and transparency in clinical work. CONCLUSIONS: Repeated exposure to stressful events potentiates burnout, wherein staff no longer experience satisfaction and enjoyment in what they do. This paper presents the behavioural responses that experienced Intensivists described in relation to stressful events in the ICU, including steps taken to mitigate the effects of these events on their personal well-being.

An innovative route for valorising iron and aluminium oxide rich industrial wastes: Recovery of multiple metals.

Several industrial wastes including biomass, fly ashes, red mud, mill scales, water treatment residues, have significant concentrations of metal oxides: Fe2O3, Al2O3, TiO2, SiO2 etc. Several efforts have been made towards recovering metals within these wastes. Rather than recovering one metal at a time, we report a novel approach for simultaneously extracting multiple metals from mixed oxides in a single process step. Using three distinct furnaces/heating regimes, the carbothermic reduction of Fe2O3/Al2O3/SiO2 system was investigated at 1450-1700 °C for up to 2 h over a wide composition range. Complete reduction was achieved for both Fe2O3 and SiO2 in all cases leading to the formation of Fe and Fe-Si alloys. The reduction of alumina at moderate temperatures was the key challenge. No alumina reduction was observed during reductions at 1450 °C. A partial reduction of alumina and the formation of Fe-Al alloys was detected in the Al2O3/Fe2O3/C system at 1550 °C. The formation of Fe-Si-Al alloys was also observed in the Fe2O3/SiO2/Al2O3/C system at 1550 °C. Complete reduction of alumina was observed at 1600-1700 °C, even for up to 50 wt% alumina in the system. Optimal operating conditions and reference standards were established for the simultaneous recovery of multiple metals from waste oxides. While conserving natural resources, this novel route will lower the burden on waste storage facilities with significant contributions to the economic and environmental sustainability of industrial waste management.

Genetic and pharmacological antagonism of NK1 receptor prevents opiate abuse potential.

Development of an efficacious, non-addicting analgesic has been challenging. Discovery of novel mechanisms underlying addiction may present a solution. Here we target the neurokinin system, which is involved in both pain and addiction. Morphine exerts its rewarding actions, at least in part, by inhibiting GABAergic input onto substance P (SP) neurons in the ventral tegmental area (VTA), subsequently increasing SP release onto dopaminergic neurons. Genome editing of the neurokinin 1 receptor (NK1R) in the VTA renders morphine non-rewarding. Complementing our genetic approach, we demonstrate utility of a bivalent pharmacophore with dual activity as a µ/δ opioid agonist and NK1R antagonist in inhibiting nociception in an animal model of acute pain while lacking any positive reinforcement. These data indicate that dual targeting of the dopaminergic reward circuitry and pain pathways with a multifunctional opioid agonist-NK1R antagonist may be an efficacious strategy in developing future analgesics that lack abuse potential.

Radiomic biomarkers informative of cancerous transformation in neurofibromatosis-1 plexiform tumors.

BACKGROUND: This study explores whether objective, quantitative radiomic biomarkers derived from magnetic resonance (MR), positron emission tomography (PET), and computed tomography (CT) may be useful in reliably distinguishing malignant peripheral nerve sheath tumors (MPNST) from benign plexiform neurofibromas (PN). METHODS: A registration and segmentation pipeline was established using a cohort of NF1 patients with histopathological diagnosis of PN or MPNST, and medical imaging of the PN including MR and PET-CT. The corrected MR datasets were registered to the corresponding PET-CT via landmark-based registration. PET standard-uptake value (SUV) thresholds were used to guide segmentation of volumes of interest: MPNST-associated PET-hot regions (SUV≥3.5) and PN-associated PET-elevated regions (2.0

IOIBD technical review on endoscopic indices for Crohn's disease clinical trials.

BACKGROUND: Crohn's disease (CD) is a chronic disabling and progressive IBD. Only strategies looking beyond symptoms and based on tight monitoring of objective signs of inflammation such as mucosal lesions may have the potential for disease modification. Endoscopic evaluation is currently the gold standard to assess mucosal lesions and has become a major therapeutic endpoint in clinical trials. Several endoscopic indices have been proposed to evaluate disease activity; unvalidated and arbitrary definitions have been used in clinical trials for defining endoscopic response and endoscopic remission in CD. METHODS: In these recommendations from the International Organization for the Study of Inflammatory Bowel Disease, we first reviewed all technical aspects of available endoscopic scoring systems in the literature. Second, in order to achieve consensus on endoscopic definitions of remission and response in trials, a two-round vote based on a Delphi method was performed among 14 specialists in the field of IBDs. RESULTS: At the end of the voting process, the investigators ranked first a >50% decrease in Simple Endoscopic Score for Crohn's Disease (SES-CD) or Crohn's Disease Endoscopic Index of Severity for the definition of endoscopic response, and an SES-CD 0-2 for the definition of endoscopic remission in CD. All experts agreed on a Rutgeerts' score i0-i1 for the definition of endoscopic remission after surgery.

CRMPs: critical molecules for neurite morphogenesis and neuropsychiatric diseases.

Neuronal polarity and spatial rearrangement of neuronal processes are central to the development of all mature nervous systems. Recent studies have highlighted the dynamic expression of Collapsin-Response-Mediator Proteins (CRMPs) in neuronal dendritic/axonal compartments, described their interaction with cytoskeleton proteins, identified their ability to activate L- and N-type voltage-gated calcium channels (VGCCs) and delineated their crucial role as signaling molecules essential for neuron differentiation and neural network development and maintenance. In addition, evidence obtained from genome-wide/genetic linkage/proteomic/translational approaches revealed that CRMP expression is altered in human pathologies including mental (schizophrenia and mood disorders) and neurological (Alzheimer's, prion encephalopathy, epilepsy and others) disorders. Changes in CRMPs levels have been observed after psychotropic treatments, and disrupting CRMP2 binding to calcium channels blocked neuropathic pain. These observations, altogether with those obtained from genetically modified mice targeting individual CRMPs and RNA interference approaches, pave the way for considering CRMPs as potential early disease markers and modulation of their activity as therapeutic strategy for disorders associated with neurite abnormalities.

National hospitalization burden associated with spinal cord injuries in the United States.

OBJECTIVES: The objective of this study was to determine the national hospitalization burden of spinal cord injuries (SCIs) among adults in the United States. Factors predicting hospitalization outcomes including length of stay (LOS), total charges and discharge disposition of death were identified. SETTING: The study was conducted in the United States. METHODS: The 2009 Health Care Utilization Project Nationwide Inpatient Sample (HCUP-NIS) data were used in this study. Hospitalization outcomes among individuals with SCI were compared with a control group of individuals without SCI. Predictors of LOS, total charges and discharge disposition of death for SCI-related hospitalizations were determined using regression techniques. RESULTS: In 2009, there were a total of 11,848 hospitalizations because of SCI in the United States. Hospitalizations because of SCIs had 2.5 times higher LOS (12.37 (± 0.51) versus 4.93 (± 0.09), P<0.0001) and 4 times higher average charges ($142,366 (±$7430.51) versus $35,011 (±$1048.88), P<0.0001) as compared with those for the control group. The total national charge attributable to SCI-related hospitalizations was approximately $1.69 billion in 2009. Percentage of hospitalizations with discharge disposition of death was significantly higher among individuals with SCI as compared with those without SCI (5.77 versus 2.27%, P<0.0001). Different patient and hospital characteristics predicted LOS, total charges and discharge disposition of death for SCI-related hospitalizations. CONCLUSIONS: There is considerable inpatient burden associated with SCI in the United States. Inpatient LOS, charges and percentage of hospitalizations with discharge disposition of death were higher among individuals with SCI as compared with those without SCI.

The current attitudes and practices of dentists in Australia towards composite repair: A cross-sectional survey study.

BACKGROUND: Whether to replace or repair a composite restoration is controversial and varies among clinicians. This study was designed to collect information on the attitudes and practices of Australian dentists towards composite repair. METHODS: An electronic 16-item questionnaire was distributed online on Australian clinicians' dental forum with a URL address and instructions on completing the survey. The questionnaire remained accessible for 2 months. The data collected were analysed statistically using descriptive, average rank, Pearson chi-square and Kruskal-Wallis tests at α = 0.05. RESULTS: Repair of composite restorations was a widely accepted treatment modality among surveyed dentists. Despite this, approximately half of clinicians reported the prognosis of repaired restorations to be worse when compared to replacement. The most cited indications for repair were partial loss or fracture of the restoration, while the most common reason for repair was because this treatment modality was more conservative in terms of tooth structure removal. Most important patient factor influencing decision to repair composite restoration was caries risk of the patient (n = 50). Most significant situational factor to consider in decision whether to repair was previous (failed) attempts to repair (n = 74). The most important tooth level factor was the proximity of restoration to pulp (mean statistic rank 2.22). The most common composite surface treatment employed by participants bonding to old composite was acid etching (n = 87), and the main reason participants employed their chosen surface treatment was based on personal experience (n = 72). CONCLUSION: The repair of composite restorations was a commonly performed procedure that is well accepted but may still be viewed as an inferior treatment to replacement by many Australian dentists. Most dentists agreed on indications for repair restorations and surface conditioning techniques, but there was wide variation in opinions overall. Due to the lack of high-quality evidence regarding composite repair techniques, dentists tend to rely on personal experience to guide their clinical decisions.

Postoperative outcomes for unilateral congenital trochlear nerve palsy: A retrospective cohort study.

PURPOSE: Congenital trochlear nerve palsy is the most common cause of vertical strabismus. The goal of this study was to investigate surgical outcomes after superior oblique tendon plication with or without inferior oblique recession in children and adults with unilateral congenital trochlear nerve palsy. METHODS: Data and outcomes were collected in patients with a diagnosis of unilateral congenital superior oblique palsy during a retrospective single-center study conducted at the University Hospital of Tours. A reproducible, standard ophthalmological and oculomotor examination was performed pre- and postoperatively at 1 year, including presence or absence of diplopia, vertical and horizontal deviations, and compensatory head posture. Surgical success, defined as an endpoint including absence of diplopia in primary position, absence of head tilt, and vertical deviation at distance fixation<5 prism diopters (PD), was analyzed. RESULTS: A total of fifty-seven patients (median [IQR] age of 11 years [5-42]) were analyzed. Patients experienced a significant reduction in vertical distance and near deviations (p<0.001), compensatory head tilt (p < 0.001), and diplopia after surgery (p < 0.001). Surgical success was higher in adults (17/24, 70.8%) than in children (15/33, 45.5%), although this did not reach statistical significance (p=0.0657). CONCLUSION: This study suggests that plication of the superior oblique muscle tendon, with or without recession of the inferior oblique muscle, can be effective in treating unilateral congenital trochlear nerve palsy. Further studies are necessary to compare surgical procedures and investigate their efficacy in adults compared to children in the short and long term.

Severe Optic Neuropathy Induced by Very Prolonged Tedizolid as Suppressive Therapy: Description of a Case Report and Implication for Better Assessment.

The long-term tolerability of linezolid is low because of mitochondrial toxicity, whereas tedizolid may represent a better option for suppressive therapy. We report a first presumed case of tedizolid-associated optic neuropathy after a very prolonged (18-month) intake and believe that screening for optic neuropathy should be considered for patients undergoing tedizolid suppression.

Immune regulation of human herpesviruses and its implications for human transplantation.

Human herpesviruses including cytomegalovirus, Epstein-Barr virus, HHV6, HHV7, HHV8, Herpes simplex virus (HSV)-1 and HSV-2 and varicella zoster virus (VZV) have developed an intricate relationship with the human immune system. This is characterized by the interplay between viral immune evasion mechanisms that promote the establishment of a lifelong persistent infection and the induction of a broad humoral and cellular immune response, which prevents the establishment of viral disease. Understanding the immune parameters that control herpesvirus infection, and the strategies the viruses use to evade immune recognition, has been critical in understanding why immunological dysfunction in transplant patients can lead to disease, and in the development of immunological strategies to prevent and control herpesvirus associated diseases.

Use and cost of psychotropic drugs among recipients with autism in a state Medicaid fee-for-service programme.

BACKGROUND: There has been a significant increase in the prevalence of autism in the USA in the past few decades. The purpose of this study was to provide recent estimates of psychotropic drug use and costs among individuals with autism enrolled in Medicaid programme. METHOD: A cross-sectional analysis of 2007 Mississippi (MS) Medicaid fee-for-service (FFS) programme administrative-claims data was performed. Study sample included recipients (<65 years) who had a medical services claim with a diagnosis of autism in 2007. Psychotropic drug patterns of use and costs were studied. Factors predicting the use of psychotropic drugs were identified using logistic regression analyses. Average number and cost of psychotropic drug claims per recipient were reported. Costs were reported from the perspective of MS Medicaid. RESULTS: In 2007, there were 1330 recipients with a diagnosis of autism in MS Medicaid FFS programme. Among these recipients, 66.32% had a claim for psychotropic drug during the year. Roughly 39% of recipients with autism had a claim for antipsychotics, 31.58% for stimulants, 19.55% for antidepressants, 19.40% for other psychotropics and 14.81% for anxiolytics/hypnotics/sedatives. Results from regression analyses highlighted variation in psychotropic drug use by demographic and co-morbid factors. There were a total of 12,618 claims for psychotropic drugs filled by recipients with autism in 2007, at an average of 14 (±12) claims per recipient. The total cost of these claims paid for by MS Medicaid FFS programme was ∼$2 million. Antipsychotics accounted for more than half (∼58%) of the total costs, and had the highest average cost per claim ($291 ± 205). CONCLUSIONS: The results of this study indicate a high use of psychotropic drugs among individuals with autism enrolled in a state Medicaid programme. There is an urgent need to study the risk-benefit profile of these drugs in this growing population. Psychotropic drug use was found to vary by demographic and co-morbid factors. Among the different classes of psychotropic drugs, antipsychotics were the most commonly used and had the highest cost per claim.

[Impact of the French 2020 COVID-19 lockdown on the treatment and follow-up of patients with exudative age-related macular degeneration]. / Impact du confinement français en 2020 sur la prise en charge des patients atteints de dégénérescence maculaire liée à l'âge exsudative.

PURPOSE: To assess the impact of the measures taken during the lockdown period from March 17 to May 11, 2020 on the management of patients with exudative age related macular degeneration treated by intravitreal anti-VEGF injections at the University Hospital of Tours. METHODS: In this retrospective study, patients were included after analysis of the computerized medical records of patients with age related macular degeneration. Those who were treated for exudative age related macular degeneration who received at least 1 intravitreal injection in the 12 months prior and at least one consultation in the 6 months prior to the lockdown period, were included. The initial and final mean visual acuity were compared with a 5 letter non-inferiority margin. A subgroup analysis was performed according to outcomes. The visual acuities immediately after this period were also recorded. RESULTS: In all, 595 eyes of 493 patients were included. The mean initial visual acuity was 59.6 letters, vs. 58.5 for the final visual acuity, i.e. a difference of -1.13 letters with a lower limit of the confidence interval of less than 5. The visual acuity on release from lockdown was comparable to the other 2 measurements. Initial visual acuity and the number of missed treatments were the main factors associated with functional loss. CONCLUSION: Patients' visual acuity during the lockdown period was able to be maintained despite the restrictive measures and limitation of care access in France. The most common cause of substantial visual decline was missed intravitreal injections.

Harnessing a real-time location system for contact tracing in a busy emergency department.

BACKGROUND: With the persistent threat of emerging infectious diseases (EIDs), digital contact tracing (CT) tools can augment conventional CT for the prevention of healthcare-associated infectious disease transmission. However, their performance has yet to be evaluated comprehensively in the fast-paced emergency department (ED) setting. OBJECTIVE: This study compared the CT performance of a radiofrequency identification (RFID)-based real-time location system (RTLS) with conventional electronic medical record (EMR) review against continuous direct observation of close contacts ('gold standard') in a busy ED during the coronavirus disease 2019 pandemic period. METHODS: This cross-sectional study was conducted at the ED of a large tertiary care hospital in Singapore from December 2020 to April 2021. CT performance [sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and kappa] of the RTLS, EMR review and a combination of the two approaches (hybrid CT) was compared with direct observation. Finally, the mean absolute error (MAE) in the duration of each contact episode found via the RTLS and direct observation was calculated. RESULTS: In comparison with EMR review, both the RTLS and the hybrid CT approach had higher sensitivity (0.955 vs 0.455 for EMR review) and a higher NPV (0.997 vs 0.968 for EMR review). The RTLS had the highest PPV (0.777 vs 0.714 for EMR review vs 0.712 for hybrid CT). The RTLS had the strongest agreement with direct observation (kappa=0.848). The MAE between contact durations of 80 direct observations and their respective RTLS contact times was 1.81 min. CONCLUSION: The RTLS was validated to be a high-performing CT tool, with significantly higher sensitivity than conventional CT via EMR review. The RTLS can be used with confidence in time-strapped EDs for time-sensitive CT for the prevention of healthcare-associated transmission of EIDs.

Evaluating the potential of ChatGPT-4 in ophthalmology: The good, the bad and the ugly.

There is growing interest nowadays for artificial intelligence (AI) in all medical fields. Beyond the direct medical application of AI to medical data, generative AI such as "pre-trained transformer" (GPT) could significantly change the ophthalmology landscape, opening up new avenues for enhancing precision, productivity, and patient outcomes. At present, ChatGPT-4 has been investigated in various ways in ophthalmology for research, medical education, and support for clinical decisions purposes. This article intends to demonstrate the application of ChatGPT-4 within the field of ophthalmology by employing a 'mise en abime' approach. While we explore its potential to enhance the future of ophthalmology care, we will also carefully outline its current limitations and potential risks.

Advances in direct T-cell alloreactivity: function, avidity, biophysics and structure.

Although T-cell-based adaptive immunity plays a crucial role in protection against infectious pathogens and uncontrolled outgrowth of malignant cells, a large portion of these T cells are also capable of responding to allogeneic HLA molecules, violating the paradigm of self-major histocompatibility complex (MHC) restriction. Recent studies have provided insights into the mechanisms by which these T cells recognize allogeneic targets. The role of antiviral T cells in direct alloreactivity through peptide-dependent molecular mimicry and alternate peptide-MHC docking modes has emerged as major models for the human alloresponse. Here, we review in depth recent advances in this field and discuss how molecular interactions between T cells and HLA molecules drive the activation of these effector cells and its potential implications for alloreactivity in human transplantation.

Long-term ophthalmological outcomes in patients with anterior plagiocephaly managed with a fronto-orbital advancement procedure.

BACKGROUND: Anterior plagiocephaly results from early fusion of a unilateral coronal cranial suture, which affects 1/10,000 infants at birth and can be associated with ophthalmological complications. The study aimed to evaluate the frequency of oculomotor disorders and refractive errors in children with non-syndromic anterior plagiocephaly. METHODS: Patients with anterior plagiocephaly undergoing surgery using a fronto-orbital advancement technique were included in this retrospective study between 2011 and 2017. The following data were collected: cycloplegic refraction in diopters (D), best-corrected visual acuity, manifest strabismus in primary position, ocular motility, head tilt in primary position, slit-lamp and fundus examination. The refractive errors were determined by autorefraction after cycloplegia with cyclopentolate. RESULTS: Among the sixteen patients included, hyperopia >2.5D was found in 10 patients, astigmatism >1D in 10 patients and anisometropia >1D in 7 patients. Astigmatism was contralateral to the synostosis in 7 cases. In total, significant refractive errors were found in 92.9%. Amblyopia was found in 33.3% patients. Strabismus was found in 11 patients, most frequently combined horizontal and vertical, of which 4 required strabismus surgery. The most frequent vertical deviation was ipsilateral hypertropia in 54.5%. We found superior oblique muscle limitation in 3 patients. Optic disc pallor was found in 2 patients. CONCLUSION: In the years following fronto-orbital advancement for non-syndromic anterior plagiocephaly, refractive errors and oculomotor disorders are frequently encountered, mainly contralateral astigmatism and strabismus with both horizontal deviation and ispilateral hypertropia.

Impact of the first lockdown related to the COVID-19 pandemic on ophthalmic emergencies in a French University Hospital.

INTRODUCTION: At the beginning of the COVID-19 pandemic, the French government implemented its first national lockdown between March and May 2020 in order to limit the dissemination of the virus. This historic measure affected patients' daily lives and transportation, resulting in changes in the delivery of medical care, particularly emergency care. This study aimed to assess the impact of this restriction policy on the number and severity of ophthalmic emergencies seen in an ophthalmology emergency department. METHODS: This retrospective study conducted at the regional university Hospital of Tours included all patients presenting to the ophthalmology emergency department over four periods: lockdown (03/16/2020 to 05/10/2020), post-lockdown (05/11/2020 to 06/12/2020) and the two corresponding periods in 2019. The following data were recorded: sex, age, time of visit, reason for visit, diagnosis, severity of emergency graded on the BaSe SCOrE, time from first symptoms until visit, existence of a work-related injury, and referral source (ophthalmologist or other). RESULTS: A total of 1186 and 1905 patients were respectively included during the 2020 lockdown period and the corresponding period in 2019. The study populations for the 2019 and 2020 post-lockdown periods consisted of 1242 and 1086 patients respectively. During the lockdown, the number of consultations decreased significantly (-37.7%), affecting mild and severe emergencies similarly. During the post-lockdown period, the number of emergencies gradually increased but did not reach the level of the corresponding period in 2019 (-12.6%). CONCLUSION: The first French lockdown resulted in a significant decrease in ophthalmic emergency visits, similar for all levels of severity. All age groups were impacted similarly, without the expected exaggerated decrease for patients over 50 years of age, who are considered to be at greater risk for developing a severe form of COVID-19. The post-lockdown period showed a gradual increase in ophthalmic emergency visits, although these remained fewer than the previous year.