Determinants of beta-lactam PK/PD target attainment in critically ill patients: A single center retrospective study.

PURPOSE: We aimed to identify factors associated with achieving target BL plasma concentrations and describe real world data for therapeutic drug monitoring (TDM). METHODS: A retrospective single center study was conducted. We collected data from patients admitted to ICU with at least one BL TDM. We assessed the proportion of patients attaining the recommended plasma concentrations (i.e 100%fT > 4 to 8 MIC). Univariate and multivariate analyses was performed to identify the determinants of BL target attainment. RESULTS: 156 patients were included. At the first dosing, 34% achieved target BL plasma concentrations, 50% were overdosed, and 16% were underdosed. Median time for 1st TDM were 4 (SD = 2.9) days. Multivariate analysis revealed that CKD-EPI estimated glomerular filtration rate (OR = 1.02; CI [1.01; 1.03]; p < 0.0001) and total body weight (OR = 1.03; CI [1.01; 1.04]; p = 0.0048) were the main determinant of BL target attainment. Conversely, Continuous Renal Replacement Therapy (OR = 0.28; CI [0.09; 0.89]; p = 0.0318) and meropenem use (OR = 0.31; CI [0.14; 0.69]; p = 0.0041) were identified as risk factors for overdosing. No factor was associated with underdosing. CONCLUSION: Achieving target BL plasma concentrations remains challenging in ICUs. Identifying predictive factors of BL target attainment would favor implementing rapid dosing optimization strategies in both under and overdosing high risk patients.

The intersection of Growth Mindset and Accreditation in Pharmacy Education.

OBJECTIVE: To describe existing growth mindset literature within pharmacy and healthcare education, describe how a growth mindset can be beneficial in the accreditation process, and propose potential ways to promote a growth mindset in faculty, preceptors, students, and staff within pharmacy education. FINDINGS: To help pharmacy learners develop a growth mindset, existing literature emphasizes the need for a shift toward and aligning assessment with growth mindset, helping to create self-directed adaptive learners, leading to healthcare providers who can adjust their practice to tackle expected and unexpected challenges throughout their careers. Strategies to create a culture of growth mindset identified include training faculty and learners on growth mindset and developing new assessments that track a learner's growth. Recommendations for pharmacy educators include encouraging educators to assess their own growth mindset and use a variety of teaching methods and provide feedback on learner effort that encourages the process of learning rather than focusing on individual attributes, traits, and results. SUMMARY: Growth mindset intersects with accreditation standards for both professional degree programs and providers of continuing pharmacy education. Continuing professional development process (CPD) is one way to encourage faculty, staff, and students to develop a growth mindset. While a growth mindset can have many positive impacts on pharmacy accreditation, it is essential to recognize that achieving and maintaining accreditation is a multifaceted process involving numerous factors. A growth mindset can positively influence pharmacy education accreditation by fostering a culture of continuous improvement, innovation, resilience, student-centeredness, data-driven decision-making, collaboration, and effective leadership.

Scale-up of the Internet-based Professional Learning to help teachers promote Activity in Youth (iPLAY) intervention: a hybrid type 3 implementation-effectiveness trial.

BACKGROUND: Whole-of-school programs have demonstrated success in improving student physical activity levels, but few have progressed beyond efficacy testing to implementation at-scale. The purpose of our study was to evaluate the scale-up of the 'Internet-based Professional Learning to help teachers promote Activity in Youth' (iPLAY) intervention in primary schools using the RE-AIM framework. METHODS: We conducted a type 3 hybrid implementation-effectiveness study and collected data between April 2016 and June 2021, in New South Wales (NSW), Australia. RE-AIM was operationalised as: (i) Reach: Number and representativeness of students exposed to iPLAY; (ii) Effectiveness: Impact of iPLAY in a sub-sample of students (n = 5,959); (iii) Adoption: Number and representativeness of schools that received iPLAY; (iv) Implementation: Extent to which the three curricular and three non-curricular components of iPLAY were delivered as intended; (v) Maintenance: Extent to which iPLAY was sustained in schools. We conducted 43 semi-structured interviews with teachers (n = 14), leaders (n = 19), and principals (n = 10) from 18 schools (11 from urban and 7 from rural locations) to determine program maintenance. RESULTS: Reach: iPLAY reached ~ 31,000 students from a variety of socio-economic strata (35% of students were in the bottom quartile, almost half in the middle two quartiles, and 20% in the top quartile). EFFECTIVENESS: We observed small positive intervention effects for enjoyment of PE/sport (0.12 units, 95% CI: 0.05 to 0.20, d = 0.17), perceptions of need support from teachers (0.26 units, 95% CI: 0.16 to 0.53, d = 0.40), physical activity participation (0.28 units, 95% CI: 0.10 to 0.47, d = 0.14), and subjective well-being (0.82 units, 95% CI: 0.32 to 1.32, d = 0.12) at 24-months. Adoption: 115 schools received iPLAY. IMPLEMENTATION: Most schools implemented the curricular (59%) and non-curricular (55%) strategies as intended. Maintenance: Based on our qualitative data, changes in teacher practices and school culture resulting from iPLAY were sustained. CONCLUSIONS: iPLAY had extensive reach and adoption in NSW primary schools. Most of the schools implemented iPLAY as intended and effectiveness data suggest the positive effects observed in our cluster RCT were sustained when the intervention was delivered at-scale. TRIAL REGISTRATION: ACTRN12621001132831.

Auditory performance after cochlear reimplantation.

AIM: The aim of this study was to evaluate the impact of cochlear reimplantation (CR) on hearing performance in children and adults with severe to profound hearing loss. MATERIAL AND METHODS: Retrospective observational study. OBJECTIVES: The main objective of this study was to determine whether there was a difference in hearing performance before and after CR. Secondary objectives were to analyze reasons for CR; to assess correlations between auditory performance and complete electrode reinsertion during CR, age, gender, explantation-to-CR interval, and interval between first implantation and CR; and to assess difference in APCEI score and the French evaluation protocol for implanted patients before and after CR. RESULTS: Comparison of speech perception scores before and after explantation-reimplantation showed no significant difference (P>0.005) at 1 year or at 2 years after CR. In 80% of cases, reimplantation was due to hard implant failure. In other cases, it was undertaken for soft failure (diminished performance but no abnormalities on integrity testing) (8%), medical reasons (6%), or undetermined reasons (6%). There was no significant correlation between auditory performance at 1 or 2 years and complete or incomplete reinsertion of electrodes, age, gender, explantation-to-CR interval, or interval between first implantation and CR (P>0.005). For the adult subgroup, the French evaluation protocol scores did not differ after reimplantation (P=0.62). Likewise, for the child sub-group, APCEI and CAP results did not deteriorate after reimplantation. CONCLUSION: Reimplantation had no negative impact on hearing and speech perception, but provided performance equivalent to or better than after initial implantation.

[The evolution of child psychiatry emergencies: Results and reflections from a Nancy University Hospital study]. / Réflexion sur l'évolution à 10 ans des urgences pédopsychiatriques, CHRU-Nancy.

INTRODUCTION: Mental illness is one of the most common causes of disability, morbidity and mortality in childhood. According to the scientific literature, the prevalence of mental health disorders is an estimated 10% to 20% in the USA and similar results are found in France. Although primordial, outpatient care often appears insufficient with inequalities in its geographical distribution and its accessibility. These past decades have been marked by an increase in consultations for mental disorders in pediatric emergency departments. Is this trend indicative of a "defect" in the healthcare organization? Identifying the root causes of this inflation in psychiatric consultations seems of paramount importance in the improvement of healthcare policies. In France and worldwide, only a few studies deal with this subject. That is why we proposed to observe the evolution of the number of consultations for mental health reasons in the pediatric emergency department of Nancy University Hospital and to detail their characteristics. MATERIALS AND METHODS: Ancillary comparative and retrospective study (2003-2013) on minors having received a child psychiatry consultation within the pediatric emergency department of Nancy University Hospital. RESULTS: The number of consultations for mental health reasons increased by 119% (97 in 2003; 212 in 2013), while consultations for pediatrics reasons remained stable over the period studied. Consultations mainly dealt with females representing 55.6% of consultations in 2003 and 63.7% in 2013. Mean age of consultants was stable: 13.9 years (standard deviation=3.3 years) in 2003; 14.1 (2.5) years in 2013. Family structure witnessed a three-fold increase in the single-parent model. Regarding consultation motives, behavioral disorders were significantly more represented in 2013: 27.7% (RR=1.7; 95% CI 1.0-2.8; P<0.05) versus 16.5%. As far as diagnosis is concerned (ICD-10), emotional and behavioral disorders increased to 35.9% from 12.6% (RR=2.8; IC95% 1.6-5.1; P=0.0001). CONCLUSIONS: In France, as well as in other western countries, the number of visits in pediatric emergency departments for mental health reasons more than doubled over a 10-year span. This growth mostly concerned externalizing disorders as a motive for consultation. Causes for this increase are multifactorial and closely related to the prevalence of psychiatric disorders in children. Some studies showed that economic factors played a major role on mental illness during such a downturn as the financial crisis of 2007-2008. Unemployment caused by economic crises can weaken pediatric caregivers and therefore their patients. Evolution of family structure and value also explains this trend. These past decades, the two-parent model, relevant till the 1960s, has evolved to a point where single parents are more quickly overwhelmed. Family values are now focused on consensus rather than duty and hedonism has become a central value. Women are more involved in the working world which became for all a performance field. Several studies have shown that social settings where competitiveness is the norm breed externalized disorders in children by advocating short-term efficiency. Moreover, the widespread use of screens in households as well as early exposure impact the psychomotor development, decrease the amount of sleep and may be responsible for the occurrence of many psychiatric disorders. There are some epidemiological reasons too. In 1971, Omran introduced a concept called "epidemiological transition" explaining how mental health issues appeared in the limelight through to the decline of infectious and cardiovascular diseases. This phenomenon has already occurred in western countries which could explain the increase in the prevalence of psychiatric disorders. In Africa, there is evidence it may have already started. Beyond all these considerations, the increase in consultations for mental disorders in pediatric emergency departments can be explained by a change in care consumption habits. Going straight to the local emergency department, accessible on a 24/7 basis, is easier than waiting for an outpatient appointment and is also free for the have-nots lacking proper insurance coverage. Scarce resources in ambulatory care may also explain the increased recourse to emergency services. Several reports have shown a lack of child psychiatrists and their uneven geographical distribution. For example, in the US only a third of children with mental disorders receive proper care, a lack which doubled between 1997 and 2010. Despite the reason for this trend, it is important to propose a better fitting of the healthcare system to the population needs, and to improve prevention and early identification. All these changes require further collective reflection.

Testing Critical Slowing Down as a Bifurcation Indicator in a Low-Dissipation Dynamical System.

We study a two-dimensional low-dissipation nonautonomous dynamical system, with a control parameter that is swept linearly in time across a transcritical bifurcation. We investigate the relaxation time of a perturbation applied to a variable of the system and we show that critical slowing down may occur at a parameter value well above the bifurcation point. We test experimentally the occurrence of critical slowing down by applying a perturbation to the accessible control parameter and we find that this perturbation leaves the system behavior unaltered, thus providing no useful information on the occurrence of critical slowing down. The theoretical analysis reveals the reasons why these tests fail in predicting an incoming bifurcation.

[Cervicofacial nontuberculous mycobacteria in children: Clinical, microbiological and therapeutic features. A retrospective study and literature review]. / Adénites cervico-faciales à mycobactéries atypiques de l'enfant : caractéristiques cliniques, microbiologiques et thérapeutiques. Étude rétrospective et revue de la littérature.

BACKGROUND: Nontuberculous mycobacteria (NTM) is a common cause of lymphadenitis. A rise in incidence has been reported. Our main aim was to describe the clinical features, microbiological aspects and treatment of the disease. METHODS: We conducted a retrospective, monocentric study between January 2008 and December 2017 (University Hospital of Nantes). INCLUSION CRITERIA: age<18 years, 1 positive lymph node specimen with identification of the species in culture, head-and-neck localization. RESULTS: Forty-nine patients were enrolled from 2008 to 2017. Median age was 28 months (range: 6-141 months). Median time to confirmation of diagnosis was 2.1 months (range: 0.7-6 months). The sites encountered were mandibular (45%), cervical (33%), and parotid (16%). The main clinical signs were a tender nodule (70%), purplish nodule (59%) or painless nodule (83%), without fever (88%). The species identified were: Mycobacterium avium (n=26), M. lentiflavum (n=13), M. intracellulare (n=7), M. malmoense (n=2) and M. scrofulaceum (n=1). Antibiotic treatment was frequent (77% of cases). DISCUSSION: This study is the second largest French cohort of NTM lymphadenitis in children with microbiological confirmation. The most frequent presentation was a tender, purplish, and painless mandibular nodule. The predominant species was M. avium. M. lentiflavum, which emerged during our study, does not figure in any European studies before 2014 but appears in the most recent studies. The effects of discontinuation of mandatory BCG immunization in France in NMT is not statistically demonstrable here due to lack of relevant data prior to 2007. CONCLUSION: A possible diagnosis of NTM lymphadenitis should not be overlooked in children presenting painless, purplish, cervicofacial tumefaction.

Reduced progression of bone erosion in cytomegalovirus seropositive rheumatoid arthritis patients.

BACKGROUND: Human cytomegalovirus (HCMV) seropositivity has been associated with higher inflammation during rheumatoid arthritis (RA). However, no data are available on the impact of HCMV seropositivity on bone erosion progression during RA. METHODS: We selected 487 individuals of ESPOIR cohort who fulfilled the 2010 ACR/EULAR criteria for RA. HCMV serology for these patients was determined using Architect CMV IgG assay. Baseline and 1-year central X-ray reading using modified Total Sharp Score (mTSS), Erosion Sharp Score, and joint space narrowing Sharp score were used to quantify structural damage progression. We performed univariate and multivariate analyses to investigate the association between HCMV status and bone erosion progression. RESULTS: We analyzed 273 HCMV seropositive (HCMV+) and 214 HCMV seronegative (HCMV-) RA patients. At inclusion, HCMV+ patients were less frequently ACPA+ (49.8% versus 58.9%, p < 0.0465) and had a higher DAS28-ESR (5.55 ± 1.24 versus 5.20 ± 1.14, p < 0.0013) in comparison with HCMV-. At 1 year, bone erosion progression (delta erosion Sharp score > 1 point) was lower in HCMV+ patients (16.1% versus 25.2%, p = 0.0128) in comparison with HCMV-. HCMV+ status remained independently associated with lower bone erosion progression in multivariate analysis. CONCLUSIONS: Our findings suggest that, independently of other confounding factors, HCMV seropositivity is associated with a lower progression of bone erosion during RA.

[Interest and difficulties in setting up pharmaceutical reconciliations for patients with dressings for complex wounds]. / Intérêts et difficultés de mise en place de conciliations pharmaceutiques pour les patients porteurs de pansements pour plaies complexes.

OBJECTIVES: The management of wounds is a commonplace activity in a patient's healthcare pathway. The involvement of the pharmacist in the management of complex dressings can help strengthen the continuity of this care thanks to the pharmaceutical reconciliation. The objective of this study was to improve the quality of information transmitted between the city and the hospital regarding complex wound dressings. METHODS: This is a prospective study consisting of two groups in three services (medicine, diabetology, vascular surgery): the control group corresponded to a classic patient care and in the intervention group, the pharmacists performed dressing reconciliations. A follow-up of the patients after coming back home was realized with healthcare professionals of city involved. RESULTS: Twenty patients were included in the control group and 19 in the intervention group. Entry conciliation has improved the quality and quantity of information on wounds transmitted between the city and the hospital. Exit conciliation has increased from 60 to 100% wound and dressing output prescriptions. One hundred percent of nurses surveyed were satisfied with the patients care. CONCLUSIONS: Reconciliation would improve information transmitted between the city and the hospital and avoid a break in the continuity of complex wounds cares. However, the time dedicated and the adhesion of the care services were difficulties encountered. This study is the first highlighting the interest of medical device reconciliation and could allow reconciliation extension toward other medical devices.

[Acute carpal tunnel syndrome caused by a thrombosis of a persistent median artery: 2 case reports]. / Canal carpien aigu : penser à la thrombose de l'artère persistante du nerf médian !

Carpal tunnel syndrome is a common peripheral neuropathy, usually idiopathic or post-traumatic due to the compression of the median nerve. Numbness and paresthesias in the median nerve distribution are the most common symptoms associated with this condition. Persistent median artery is a rare anatomic variation, thrombosis of this additional artery can be responsible for an acute carpal tunnel syndrome, and patients frequently complain about coldness and acute hand swelling. These unusual features must lead clinicians to think of a vascular cause. The diagnosis can be easily confirmed by using ultrasound doppler, but CT-scan and MRI are sometimes helpful. We describe 2 cases of acute carpal tunnel syndrome due to thrombosed persistent median artery, including a case of thromboangiitis obliterans. These thrombosis might also be due to traumatic causes. No guidelines are currently available to help physicians for the management of carpal tunnel syndrome from thrombosed persistent median artery. Antiplatelet therapy, statin, anticoagulant might be helpful, and surgery has sometimes be reported as effective.

Inflammatory cell distribution in colon mucosa as a new tool for diagnosis of irritable bowel syndrome: A promising pilot study.

BACKGROUND: Currently, there are no histological criteria to diagnose irritable bowel syndrome (IBS). Our aims were (i) to examine the distribution of inflammatory cells in the colon of healthy and IBS subjects and (ii) to find histological diagnosis criteria for IBS. METHODS: Colonic biopsies were taken from four distinct regions of the colon from 20 controls (HC) and 11 patients with IBS (4 with constipation (IBS-C) and 7 with diarrhea (IBS-D) and embedded in paraffin. Macrophages, mast cells, eosinophils, and T lymphocytes were immunostained and positive cells counted. KEY RESULTS: In both HC and IBS patients, global cellularity decreased from the cecum to the rectum (P < .01) which is attributed to reduced number of macrophages (P < .05) and eosinophils (P < .001) but not T cells. Mast cells were reduced in IBS (P < .05) but not in HC, particularly in IBS-D (P < .05). Results showed higher number of macrophages in the left colon of IBS subjects than HC (P < .05). CONCLUSION & INFERENCES: Here we report a decreasing gradient of immune cells from the cecum to the rectum of the human colon. Although global cellularity cannot be used to distinguish between IBS and HC, closer analysis of macrophages and mast cells may be useful markers to confirm IBS histologically and to differentiate between IBS-C and IBS-D when clinical presentation alternates between constipation and diarrhoea. This pilot study remains to be confirmed with greater number of patients.

Circulating endothelial progenitors in vascular repair.

Endothelial Colony Forming Cells (ECFCs) are obtained in culture from Circulating Endothelial Progenitor Cells. They display all characteristics of endothelial cells and they display stem cells features. Cord blood-derived ECFCs (CB-ECFCs) have a high clonogenic and proliferative potentials, and exhibit vascular repair capabilities useful for the treatment of ischemic diseases. However, the link between immaturity and functional properties of CB-ECFCs is still poorly defined. We showed that these cells have a high clonogenic potential and are capable to be efficiently reprogrammed into induced pluripotent stem cells. Moreover, we analyzed the expression of a broad panel of genes involved in embryonic stem cell properties. We define a novel stem cell transcriptional signature for CB-ECFCs fora better characterization and stratification according to their stem cell profile. We then improved the yield of CB-ECFC production for obtaining cells more functional in fewer passages. We used Glycosaminoglycans (GAG), components from the extracellular matrix which potentiate heparin binding growth factor activities. GAG mimetics were designed, having the capacity to increase the yield of ECFC during the isolation process, to increase the number of colonies, improve adhesion, proliferation, migration and self-renewal. GAG mimetics have thus great interest for vascular regeneration in combination with ECFC. Our results show that CB-ECFC are immature cells harboring specific functions such as formation of colonies, proliferation and formation of vascular structures in vitro and in vivo.

Sphingosine-1-phosphate receptor-1 (S1P1) is expressed by lymphocytes, dendritic cells, and endothelium and modulated during inflammatory bowel disease.

The sphingosine-1-phosphate receptor-1 (S1P1) agonist ozanimod ameliorates ulcerative colitis, yet its mechanism of action is unknown. Here, we examine the cell subsets that express S1P1 in intestine using S1P1-eGFP mice, the regulation of S1P1 expression in lymphocytes after administration of dextran sulfate sodium (DSS), after colitis induced by transfer of CD4+CD45RBhi cells, and by crossing a mouse with TNF-driven ileitis with S1P1-eGFP mice. We then assayed the expression of enzymes that regulate intestinal S1P levels, and the effect of FTY720 on lymphocyte behavior and S1P1 expression. We found that not only T and B cells express S1P1, but also dendritic (DC) and endothelial cells. Furthermore, chronic but not acute inflammatory signals increased S1P1 expression, while the enzymes that control tissue S1P levels in mice and humans with inflammatory bowel disease (IBD) were uniformly dysregulated, favoring synthesis over degradation. Finally, we observed that FTY720 reduced T-cell velocity and induced S1P1 degradation and retention of Naïve but not effector T cells. Our data demonstrate that chronic inflammation modulates S1P1 expression and tissue S1P levels and suggests that the anti-inflammatory properties of S1PR agonists might not be solely due to their lymphopenic effects, but also due to potential effects on DC migration and vascular barrier function.