Early life poly- and perfluoroalkyl substance levels and adiposity in the first 2 years of life.

IMPORTANCE: Poly- and perfluoroalkyl substances (PFASs) are nondegradable, man-made chemicals. They accumulate in humans with potential harmful effects, especially in susceptible periods of human development, such as the first months of life. We found that, in our cohort, exclusively breastfed (EBF) infants had 3 times higher PFAS plasma levels compared with exclusively formula-fed (EFF) infants at the age of 3 months. Thus, PFASs could potentially reduce the health benefits of breastfeeding. OBJECTIVE: We investigated the associations between PFAS levels at the age of 3 months and accelerated gain in fat mass during the first 6 months of life, body composition at 2 years, and whether these associations differ between EBF and EFF infants. SETTING: In 372 healthy term-born infants, we longitudinally assessed anthropometrics, body composition (by air-displacement plethysmography and dual-energy X-ray absorptiometry), and visceral and subcutaneous fat (by abdominal ultrasound) until the age of 2 years. MEASURES: The plasma levels of 5 individual PFASs were determined by liquid chromatography-electrospray ionization-tandem mass spectrometry at the age of 3 months. MAIN OUTCOMES: We studied associations between PFAS levels and outcomes using multiple regression analyses. RESULTS: Higher early life plasma perfluorooctanoic acid and total PFAS levels were associated with an accelerated gain in fat mass percentage [FM%; >0.67 SD score (SDS)] during the first 6 months of life. Higher early life PFAS levels were associated with lower fat-free mass (FFM) SDS at the age of 2 years, but not with total FM% SDS at 2 years. Furthermore, we found opposite effects of PFAS levels (negative) and exclusive breastfeeding (positive) at the age of 3 months on FFM SDS at 2 years. CONCLUSION: Higher PFAS levels in early life are associated with accelerated gains in FM% during the first 6 months of life and with lower FFM SDS at the age of 2 years, which have been associated with an unfavorable body composition and metabolic profile later in life. Our findings warrant further research with longer follow-up times.

Ensuring quality in 17OHP mass spectrometry measurement: an international study assessing isomeric steroid interference.

OBJECTIVES: Interference from isomeric steroids is a potential cause of disparity between mass spectrometry-based 17-hydroxyprogesterone (17OHP) results. We aimed to assess the proficiency of mass spectrometry laboratories to report 17OHP in the presence of known isomeric steroids. METHODS: A series of five samples were prepared using a previously demonstrated commutable approach. These samples included a control (spiked to 15.0 nmol/L 17OHP) and four challenge samples further enriched with equimolar concentrations of 17OHP isomers (11α-hydroxyprogesterone, 11ß-hydroxyprogesterone, 16α-hydroxyprogesterone or 21-hydroxyprogesterone). These samples were distributed to 38 participating laboratories that reported serum 17OHP results using mass spectrometry in two external quality assurance programs. The result for each challenge sample was compared to the control sample submitted by each participant. RESULTS: Twenty-six laboratories (68 % of distribution) across three continents returned results. Twenty-five laboratories used liquid chromatography-tandem mass spectrometry (LC-MS/MS), and one used gas chromatography-tandem mass spectrometry to measure 17OHP. The all-method median of the control sample was 14.3 nmol/L, ranging from 12.4 to 17.6 nmol/L. One laboratory had results that approached the lower limit of tolerance (minus 17.7 % of the control sample), suggesting the isomeric steroid caused an irregular result. CONCLUSIONS: Most participating laboratories demonstrated their ability to reliably measure 17OHP in the presence of the four clinically relevant isomeric steroids. The performance of the 12 (32 %) laboratories that did not engage in this activity remains unclear. We recommend that all laboratories offering LC-MS/MS analysis of 17OHP in serum, plasma, or dried bloodspots determine that the isomeric steroids are appropriately separated.

Unraveling Dexamethasone-Induced Neurobehavioral and Sleep Problems in Children With ALL: Which Determinants Are Important?

PURPOSE: Dexamethasone, the preferred corticosteroid in most treatment protocols for pediatric acute lymphoblastic leukemia (ALL), can induce undesirable side effects. Neurobehavioral and sleep problems are frequently reported, but the interpatient variability is high. We therefore aimed to identify determinants for parent-reported dexamethasone-induced neurobehavioral and sleep problems in pediatric ALL. METHODS: Our prospective study included patients with medium-risk ALL and their parents during maintenance treatment. Patients were assessed before and after one 5-day dexamethasone course. Primary end points were parent-reported dexamethasone-induced neurobehavioral and sleep problems, measured with the Strengths and Difficulties Questionnaire and Sleep Disturbance Scale for Children, respectively. Analyzed determinants included patient and parent demographics, disease and treatment characteristics, parenting stress (Parenting Stress Index and Distress Thermometer for Parents), dexamethasone pharmacokinetics, and genetic variation (candidate single-nucleotide polymorphisms rs41423247 and rs4918). Statistically significant determinants identified in univariable logistic regression analyses were incorporated in a multivariable model. RESULTS: We included 105 patients: median age was 5.4 years (range, 3.0-18.8) and 61% were boys. Clinically relevant dexamethasone-induced neurobehavioral and sleep problems were reported by parents in 70 (67%) and 61 (59%) patients, respectively. In our multivariable regression models, we identified parenting stress as a significant determinant for parent-reported neurobehavioral (odds ratio [OR], 1.16; 95% CI, 1.07 to 1.26) and sleep problems (OR, 1.06; 95% CI, 1.02 to 1.10). Furthermore, parents who experienced more stress before start of a dexamethasone course reported more sleep problems in their child (OR, 1.16; 95% CI, 1.02 to 1.32). CONCLUSION: We identified parenting stress, and not dexamethasone pharmacokinetics, genetic variation, patient/parent demographics, or disease/treatment characteristics, as a significant determinant for parent-reported dexamethasone-induced neurobehavioral and sleep problems. Parenting stress may be a modifiable target to reduce these problems.

The importance of ligand gated ion channels in sleep and sleep disorders.

On average, humans spend about 26 years of their life sleeping. Increased sleep duration and quality has been linked to reduced disease risk; however, the cellular and molecular underpinnings of sleep remain open questions. It has been known for some time that pharmacological modulation of neurotransmission in the brain can promote either sleep or wakefulness thereby providing some clues about the molecular mechanisms at play. However, the field of sleep research has developed an increasingly detailed understanding of the requisite neuronal circuitry and key neurotransmitter receptor subtypes, suggesting that it may be possible to identify next generation pharmacological interventions to treat sleep disorders within this same space. The aim of this work is to examine the latest physiological and pharmacological findings highlighting the contribution of ligand gated ion channels including the inhibitory GABAA and glycine receptors and excitatory nicotinic acetylcholine receptors and glutamate receptors in the sleep-wake cycle regulation. Overall, a better understanding of ligand gated ion channels in sleep will help determine if these highly druggable targets could facilitate a better night's sleep.

Specificities of Meningitis and Meningo-Encephalitis After Kidney Transplantation: A French Retrospective Cohort Study.

Kidney transplant recipients develop atypical infections in their epidemiology, presentation and outcome. Among these, meningitis and meningoencephalitis require urgent and adapted anti-infectious therapy, but published data is scarce in KTRs. The aim of this study was to describe their epidemiology, presentation and outcome, in order to improve their diagnostic and management. We performed a retrospective, multicentric cohort study in 15 French hospitals that included all 199 cases of M/ME in KTRs between 2007 and 2018 (0.9 case per 1,000 KTRs annually). Epidemiology was different from that in the general population: 20% were due to Cryptococcus neoformans, 13.5% to varicella-zoster virus, 5.5% to Mycobacterium tuberculosis, and 4.5% to Enterobacteria (half of which produced extended spectrum beta-lactamases), and 5% were Post Transplant Lymphoproliferative Disorders. Microorganisms causing M/ME in the general population were infrequent (2%, for Streptococcus pneumoniae) or absent (Neisseria meningitidis). M/ME caused by Enterobacteria, Staphylococci or filamentous fungi were associated with high and early mortality (50%-70% at 1 year). Graft survival was not associated with the etiology of M/ME, nor was impacted by immunosuppression reduction. Based on these results, we suggest international studies to adapt guidelines in order to improve the diagnosis and the probabilistic treatment of M/ME in SOTRs.

A conceptual framework to develop a patient-reported experience questionnaire on the cystic fibrosis journey in France: the ExPaParM collaborative study.

BACKGROUND: The objective of the study was to elaborate a conceptual framework related to the domains of patient experience along the cystic fibrosis (CF) journey from the patients and parents of children with CF to inform the design of a patient-reported experience questionnaire. METHOD: A collaborative research group including patients and parents with clinicians and academic researchers was set up. They identified the situations along the CF care pathway from diagnosis to paediatric care, transition to adult care and adult follow-up, transfer to transplant centres and follow-up after transplantation. Participants were recruited by CF centres in metropolitan France and overseas departments. Semi-structured interviews were conducted, transcribed verbatim and subjected to an inductive analysis conducted in duos of researchers/co-researchers using NVivo®. The conceptual framework was discussed with the research group and presented to the CF centres during two video conferences. The protocol obtained a favourable opinion from the Ethics Evaluation Committee of INSERM (IRB00003888-no. 20-700). RESULTS: The analysis led to a conceptual framework composed of domains of the CF journey, each divided into several items. 1. CF care: Management of care by the CF centre team; in-hospital care; quality of care in the community; therapeutic education and self-management support; at-home care; new therapies and research; procreation; 2. Transplant care: management of transplant and CF care; coordination with other specialties; education and self-management support; at-home care; procreation; new therapies and research; 3. Turning points along the journey: diagnosis of CF, transition to adult care, transfer to transplantation; 4. Social life with CF: housing, employment and education, social relations, social welfare and family finances. The number of patients included and the diversity of situations made it possible to achieve a sufficient richness and saturation of codes by domain to develop patient experience questionnaires. CONCLUSION: This conceptual framework, resulting from the participants' experience, will inform the design of a patient-reported experience tool, whose construct will be tested during the next phase of the ExPaParM project to assess its fidelity, intelligibility, and ability to report patient experience of the CF journey.

Poly- and perfluoroalkyl substances (PFAS) exposure through infant feeding in early life.

BACKGROUND AND AIMS: Per- and polyfluoroalkyl substances (PFAS) are non-degradable, man-made-chemicals with an elimination half-life of multiple years, causing accumulation in the environment and humans with potential harmful effects. However, longitudinal PFAS levels in human milk, daily PFAS intake and the association with infant plasma PFAS levels have never been reported. We investigated longitudinal PFOA and PFOS levels in human milk and the daily PFAS intake through infant feeding in the first 3 months of life, the most important determinants and the correlation with PFAS plasma levels at age 3 months and 2 years. METHODS: In 372 healthy term-born Dutch infants, we determined PFOA and PFOS levels in human milk given at age 1 and 3 months, in 6 infant formula brands and in infant plasma at 3 months and 2 years, using liquid-chromatography-electrospray-ionization-tandem-mass-spectrometry(LC-ESI-MS/MS). We studied the associations between daily PFAS intake and predictive characteristics by multiple regression models. RESULTS: PFOA and PFOS levels in human milk decreased between 1 and 3 months after delivery, regardless whether breastfeeding was given exclusively(EBF) or in combination with formula feeding. PFOA and PFOS could not be detected in any formula feeding. Daily PFAS intake(ng/kg) was highest in EBF-infants. Higher amount of human milk, older maternal age, lower parity and first-time breastfeeding were associated with higher daily intake. Daily PFAS intake in early life was strongly correlated with PFAS plasma levels at age 3 months and 2 years(R = 0.642-0.875, p < 0.001). CONCLUSIONS: Human milk contains PFOA and PFOS, in contrast to formula feeding. Daily PFOA and PFOS intake in early life is highest in exclusively breastfed infants and it is highly correlated with infant's plasma levels throughout infancy. Our findings show that breastfeeding is an important PFAS exposure pathway in the first months of life, with unknown but potential adverse effects. Knowing the important health benefits of breastfeeding, our findings warrant more research about the health outcomes in later life.

Collaborative research protocol to define patient-reported experience measures of the cystic fibrosis care pathway in France: the ExPaParM study.

INTRODUCTION: In France, the cystic fibrosis (CF) care pathway is coordinated by multidisciplinary teams from specialised CF centres or transplant centres. It includes the care provided at home or out of hospital, risk prevention in daily life and adjustments to social life, which together contribute to the person's quality of life. Patient experience is used to describe and evaluate the care and life of patients living with the disease. OBJECTIVES: Our collaborative research aims to identify the most significant areas and criteria that characterise the CF pathway. It will lead to the development of a questionnaire to collect patients' experience, which can be administered to all patients or parents of children registered and followed in the centres. The article describes the protocol developed in partnership with patients and parents of children living with the disease. METHOD: A multidisciplinary research group brings together researchers, patients, parents of children with CF and health care professionals. The patient partnership is involved in the 4 phases of the protocol: (1) setting up the study, recruiting patient and parent co-researchers, training them in qualitative research methods, defining the situations and profiles of patients in the study population, elaborating the protocol; (2) selecting the study sites, recruiting participants, carrying out semi-structured interviews, analysing verbatims using the grounded theory approach; (3) co-elaborating Patient-Reported Experience Measures (PREM) questionnaires adapted to the 4 types of participants: parents, adolescents, non-transplanted adults and transplanted adults; (4) validating the construct with participants and professionals from the study centres. RESULTS: The protocol obtained a favourable opinion from the Ethics Evaluation Committee of INSERM (IRB00003888-no. 20-700). Training was provided to the 5 patients and 2 parent co-researchers to enable them to participate effectively in the research. Eleven centres participated in the recruitment of participants in mainland France and Reunion Island. Eighty hours of interviews were conducted. DISCUSSION: The PREM questionnaires to be elaborated will have to undergo psychometric validation before being used by the actors of the CF network to assess the impact on the care pathways of quality approaches or new therapies available in cystic fibrosis. Trial Registration Registry: IRB00003888 - no. 20-700. Issue date: 06/09/2020.

Tapering of Etanercept is feasible in patients with Rheumatoid Arthritis in sustained remission: a pragmatic randomized controlled trial.

OBJECTIVE: In patients with rheumatoid arthritis (RA) in sustained remission, tapering of biological disease-modifying anti-rheumatic drugs can be considered. Tapering has already been investigated, but its feasibility remains to be determined. Therefore, we explored the feasibility of tapering etanercept in RA in a setting close to practice. METHOD: Patients with RA in 28-joint Disease Activity Score (DAS28) remission (≥ 6 months) and treated with etanercept 50 mg weekly (≥ 1 year) were included in the pragmatic 1 year open-label multicentre randomized controlled TapERA (Tapering Etanercept in Rheumatoid Arthritis) trial. Patients were assigned to continue etanercept weekly or to taper to every other week (EOW). Patients who lost remission [DAS28-C-reactive protein (CRP) ≥ 2.6] were re-escalated to etanercept weekly. The primary outcome was the proportion of patients maintaining DAS28-CRP remission for 6 months. RESULTS: Sixty-six patients were randomized to etanercept weekly (n = 34) or EOW (n = 32). After 6 months, 26/34 patients (76%) in the weekly and 19/32 (59%) in the EOW group maintained disease control (p = 0.136). In the EOW group, 20/32 patients (63%) remained on their tapered treatment during the trial. Two patients reintroduced weekly etanercept themselves. Ten patients were re-escalated to etanercept weekly by the rheumatologist, after a median (interquartile range) interval of 3.0 (2.0-6.0) months. Among these patients, 7/10 regained remission after re-escalation, four of them at the next study visit. CONCLUSIONS: Although non-inferiority could not be demonstrated, tapering of etanercept to EOW appeared feasible in patients in sustained remission.

Longitudinal poly- and perfluoroalkyl substances (PFAS) levels in Dutch infants.

BACKGROUND AND AIMS: Per- and polyfluoroalkyl substances (PFAS) are a potential hazard for public health. These man-made-chemicals are non-degradable with an elimination half-life of multiple years, causing accumulation in the environment and humans. Rodent studies demonstrated that PFAS are harmful, especially when present during the critical window in the first months of life. Because longitudinal data during infancy are limited, we investigated longitudinal plasma levels in infants aged 3 months and 2 years and its most important determinants. METHODS: In 369 healthy term-born Dutch infants, we determined plasma PFOS, PFOA, PFHxS, PFNA and PFDA levels at age 3 months and 2 years, using liquid chromatography-electrospray-ionization-tandem-mass-spectrometry (LC-ESI-MS/MS). We studied the associations with maternal and child characteristics by multiple regression models. RESULTS: At age 3 months, median plasma levels of PFOS, PFOA, PFHxS, PFNA and PFDA were 1.48, 2.40, 0.43, 0.23 and 0.07 ng/mL, resp. Levels decreased slightly until age 2 years to 1.30, 1.81, 0.40, 0.21 and 0.08 ng/mL, resp. Maternal age, first born, Caucasian ethnicity and exclusive breastfeeding were associated with higher infant's plasma levels at age 3 months. Levels at 3 months were the most important predictor for PFAS levels at age 2 years. Infants with exclusive breastfeeding during the first 3 months of life (EBF) had 2-3 fold higher levels throughout infancy compared to infants with exclusive formula feeding (EFF), with PFOA levels at 3 months 3.72 ng/mL versus 1.26 ng/mL and at 2 years 3.15 ng/mL versus 1.22 ng/mL, respectively. CONCLUSION: Plasma PFAS levels decreased only slightly during infancy. Higher levels at age 3 months were found in Caucasian, first-born infants from older mothers and throughout infancy in EBF-infants. Our findings indicate that trans-placental transmission and breastfeeding are the most important determinants of PFAS exposure in early life.

Belgian rheumatologists' preferences regarding measures of disease activity in patients with rheumatoid arthritis: results from a mixed-methods study.

The reliability and clinical usefulness of the different composite disease activity scores and their individual components in Rheumatoid Arthritis (RA) are still debated. This study investigated which measures of disease activity were preferred by rheumatologists. A mixed-method study was performed. First, ten Belgian rheumatologists were invited for individual interviews on their current practice and preferences for measurement of RA disease activity. Results of this qualitative study and evidence from literature served as input for developing a survey. This survey asked rheumatologists to rate preferred standard disease activity score(s), their individual components, ultrasound and related patient-reported outcomes (PROs), by maximum difference scaling. The relative importance score (RIS) for each indicator was calculated using hierarchical Bayes modeling. The qualitative study included 6/10 invited rheumatologists. Composite scores and components were perceived as useful, while PROs were found subjective. Interestingly, ultrasound was used to mediate discrepancies between physician and patient. The survey based on this was sent to 244 Belgian rheumatologists, 83/244 (34%) responded, including 66/83 (80%) complete and 17/83 (20%) incomplete surveys (two missing essential information). Most rheumatologists (75/81, 93%) used a disease activity score and 68/81 (84%) preferred the DAS28-CRP. Swollen joint count obtained the highest mean ± SD RIS (22.54 ± 2.64), followed by DAS28 ESR/CRP (20.61 ± 4.06), ultrasound (16.47 ± 7.97), CRP (13.34 ± 6.11) and physician's global assessment (12.59 ± 7.83). PROs including fatigue, pain, and patient's global assessment, and Health Assessment Questionnaire, obtained the lowest mean RIS (0.34-2.54). Rheumatologists place more faith in self-assessed disease activity components or in laboratory tests. Trust in PROs to evaluate disease activity is low in clinical practice.

Ligand gated receptor interactions: A key to the power of neuronal networks.

The discovery of the chemical synapse was a seminal finding in Neurobiology but the large body of microscopic interactions involved in synaptic transmission could hardly have been foreseen at the time of these first discoveries. Characterization of the molecular players at work at synapses and the increased granularity at which we can now analyze electrical and chemical signal processing that occur in even the simplest neuronal system are shining a new light on receptor interactions. The aim of this review is to discuss the complexity of some representative interactions between excitatory and inhibitory ligand-gated ion channels and/or G protein coupled receptors, as well as other key machinery that can impact neurotransmission and to explain how such mechanisms can be an important determinant of nervous system function.

Is intraoperative heparin during renal transplantation useful to reduce graft vascular thrombosis?

OBJECTIVES: The standard treatment for end-stage renal disease is renal transplantation. As vascular anastomoses are performed during the surgery, it may expose to a risk of vascular thrombosis. This raises the question of using intravenous heparin during the procedure. The purpose of this study was to compare the incidence of renal transplant vascular thrombosis in the perioperative period based on whether the patients received or not intraoperative heparin. METHODS: A single center retrospective study was conducted on a cohort of consecutive patients who underwent renal transplantation between 2011 and 2015. Patients were divided into two groups: patients not receiving heparin vs. receiving heparin at the dose of 0.5mg/kg. A Doppler ultrasound was performed at day one postoperatively to assess the occurrence of vascular thrombosis. Hemorrhagic complications and the need for postoperative transfusion were also assessed. RESULTS: In total, 261 patients were included. Fifty-one patients received heparin (19.5%). Patient's baseline characteristics were comparable between the groups. No significant difference was found regarding the incidence of vascular thrombosis (6% for both groups, P=1). In addition, no difference was found regarding hemorrhagic complications requiring surgical revision (P=1) as well as early postoperative transfusion rate (P=0.57). CONCLUSIONS: Our results suggest that intraoperative IV heparin doesn't improve the risk of vascular thrombosis following renal transplantation. However, intraoperative IV heparin was not significantly associated with a higher rate of hemorrhagic complications suggesting that heparin can be safely used if required in some selected patients at higher risk of thrombosis. LEVEL OF EVIDENCE: 3.

Global DNA (hydroxy)methylation is stable over time under several storage conditions and temperatures.

BACKGROUND: Epigenetic markers are often quantified and related to disease in stored samples. While, effects of storage on stability of these markers have not been thoroughly examined. In this longitudinal study, we investigated the influence of storage time, material, temperature, and freeze-thaw cycles on stability of global DNA (hydroxy)methylation. METHODS: EDTA blood was collected from 90 individuals. Blood (n = 30, group 1) and extracted DNA (n = 30, group 2) were stored at 4°C, -20°C and -80°C for 0, 1 (endpoint blood 4°C), 6, 12 or 18 months. Additionally, freeze-thaw cycles of blood and DNA samples (n = 30, group 3) were performed over three days. Global DNA methylation and hydroxymethylation (mean ± SD) were quantified using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) with between-run precision of 2.8% (methylation) and 6.3% (hydroxymethylation). Effects on stability were assessed using linear mixed models. RESULTS: global DNA methylation was stable over 18 months in blood at -20°C and -80°C and DNA at 4°C and -80°C. However, at 18 months DNA methylation from DNA stored at -20°C relatively decreased -6.1% compared to baseline. Global DNA hydroxymethylation was more stable in DNA samples compared to blood, independent of temperature (p = 0.0131). Stability of global DNA methylation and hydroxymethylation was not affected up to three freeze - thaw cycles. CONCLUSION: Global DNA methylation and hydroxymethylation stored as blood and DNA can be used for epigenetic studies. The relevance of  small differences occuring during storage depend on the expected effect size and research question.

A systematic review on the effect of DMARDs on fertility in rheumatoid arthritis.

INTRODUCTION: Drug therapy could alter fertility in patients with rheumatoid arthritis (RA). We aimed to perform a systematic review to evaluate if Disease-modifying antirheumatic drug (DMARD) therapy influences fertility as this is an important point to consider in shared decision making on RA therapy. METHODS: A search was conducted at 18/10/2019 in EMBASE, PubMed (including MEDLINE) and the Web of Science Core Collection. Our inclusion criteria were studies involving women or men diagnosed with RA, older than 18 years and on DMARD therapy, with as outcome a fertility parameter. Systematic reviews, meta-analyses, case reports, case series and animal studies were excluded. Studies not in English or Dutch or published before 2004 were excluded. Quality appraisal was performed by the CASP systematic review checklist. RESULTS: After duplicate removal, 9030 references were identified. After title/abstract screening, 82 articles remained. After full text screening, 4 articles could be retained. No studies were found through backward snowballing. Only studies involving women could be retained. The included studies investigated the effect of methotrexate, certolizumab pegol, etanercept and sulfasalazine on fertility. No detrimental effects of these DMARDs on time-to-pregnancy, anti-Müllerian hormone serum level or presence of a history of infertility, were reported. CONCLUSION: This systematic review underlines the gap in knowledge regarding the effect of DMARDs on fertility in women and especially men with RA. DMARD treatment, contrary to general belief, seemed to have no harmful effect on fertility, possibly because it resulted in better controlled disease activity. More research is needed to improve guidance for patients with RA with a child wish.

RhBMP7 use for treating scaphoid non-union: 5 cases assessed at 10 years' follow-up.

The scaphoid is the most common non-union site in the wrist. Fixation with vascularised or non-vascularised autograft is the gold standard when it comes to treating these non-unions. But, what can we offer if the autograft fails? Using osteoinductive proteins in difficult cases of long bone non-union yields good results. However, only a few studies have been published on their use for scaphoid non-union. In our study, five patients with an average age of 32 years (ranging from 21 to 44 years) with old non-union (more than 24 months) of the scaphoid were treated after autograft treatment had failed. The procedure consisted of reaming the non-union site, then adding bone autograft combined with BMP-7 (Osigraft®) in the defect and fixing it all with a screw or K-wire. Postoperative immobilisation was prescribed. Only one patient achieved bone union (20%) despite an average follow-up of 10 years (80-143 months). The average flexion-extension loss was 16.6° (0-30) relative to the contralateral side. The average strength deficit was 450 grams (0-2000) for pinch and 12.1kg (0-29) for grip compared to the contralateral side. Self-assessment questionnaires had an average PRWE at 28.9 (10.5-49) and an average QuickDASH at 28.6 (9.09-61.36). Our study could not demonstrate any real benefit of using BMP-7 for treating old scaphoid non-union despite an elevated cost. Further research is needed to look at other treatment approaches, for instance, the use of new scaffolds combining VEGF and BMP.

Provision of information on transplantation to cystic fibrosis patients and their relatives: Overview of French practices and recommendations.

BACKGROUND: How health-care professionals inform cystic fibrosis patients and their relatives about transplantation is not well known. Such information may not be provided in a timely or satisfactory manner. We conducted a survey about patient information practices among professionals from all French cystic fibrosis centers and transplant centers, to determine how they might be improved. METHODS: This was a national, retrospective, multicenter, descriptive assessment of practices involving health-care professionals, transplant recipients and their relatives, and peer patients who are themselves transplant recipients. Questionnaires were developed by the French working group on cystic fibrosis patient education (GETHEM: Groupe éducation thérapeutique et mucoviscidose). At the end of the questionnaires, respondents were invited to suggest ways to improve the current process. RESULTS: In all, 216 professionals, 55 patients, 30 relatives of these patients, and 17 peer patients responded to the questionnaires, which addressed topics in chronological order, from neonatal screening or later diagnosis of the illness to the time of the transplant, if one was performed. CONCLUSIONS: Study findings have allowed us to draft nine recommendations for professionals to improve patient information practices. A booklet now being prepared aims to facilitate the process for professionals, and e-learning modules are also forthcoming.

[Continuing professional development and recertification process in France]. / Développement professionnel continu (DPC) et émergence de la recertification en France. Évolution législative et commentaires.

Continuing medical education (CME) is an obligation in France. The evaluation of professional practices joined in 2004 the obligation to acquire knowledge, becoming the Continuing professional development (CPD) in 2009. Currently, the system is complete: definition, organization and validation. However, the individual obligation to validate the CPD has never been applied. The recertification process provided for by the 2019 law will not be operational until 2021, at the earliest. Its essential pillar is CPD. The recertification mission who prepared the law excludes all knowledge verification tests. Recertification is done by promoting the professional career path including, in addition to CPD, a maintained and regular activity, an improvement in the relationship with the patient, taking into account the doctor's health and the absence of undesirable events. Seeing that the French Medical Council oversees the professional skills of physicians, it is the Council that receives the validation of the CPD and will receive that of recertification.