Comparative therapeutic strategies for preventing aortic rupture in a mouse model of vascular Ehlers-Danlos syndrome.

Vascular Ehlers-Danlos syndrome is a rare inherited disorder caused by genetic variants in type III collagen. Its prognosis is especially hampered by unpredictable arterial ruptures and there is no therapeutic consensus. We created a knock-in Col3a1+/G182R mouse model and performed a complete genetic, molecular and biochemical characterization. Several therapeutic strategies were also tested. Col3a1+/G182R mice showed a spontaneous mortality caused by thoracic aortic rupture that recapitulates the vascular Ehlers-Danlos syndrome with a lower survival rate in males, thin non-inflammatory arteries and an altered arterial collagen. Transcriptomic analysis of aortas showed upregulation of genes related to inflammation and cell stress response. Compared to water, survival rate of Col3a1+/G182R mice was not affected by beta-blockers (propranolol or celiprolol). Two other vasodilating anti-hypertensive agents (hydralazine, amlodipine) gave opposite results on aortic rupture and mortality rate. There was a spectacular beneficial effect of losartan, reversed by the cessation of its administration, and a marked deleterious effect of exogenous angiotensin II. These results suggest that blockade of the renin angiotensin system should be tested as a first-line medical therapy in patients with vascular Ehlers-Danlos syndrome.

Hepatitis D virus interferes with hepatitis B virus RNA production via interferon-dependent and -independent mechanisms.

BACKGROUND & AIMS: Chronic coinfection with HBV and HDV leads to the most aggressive form of chronic viral hepatitis. Herein, we aimed to elucidate the molecular mechanisms underlying the widely reported observation that HDV interferes with HBV in most coinfected patients. METHODS: Patient liver tissues, primary human hepatocytes, HepaRG cells and human liver chimeric mice were used to analyze the effect of HDV on HBV using virological and RNA-sequencing analyses, as well as RNA synthesis, stability and association assays. RESULTS: Transcriptomic analyses in cell culture and mouse models of coinfection enabled us to define an HDV-induced signature, mainly composed of interferon (IFN)-stimulated genes (ISGs). We also provide evidence that ISGs are upregulated in chronically HDV/HBV-coinfected patients but not in cells that only express HDV antigen (HDAg). Inhibition of the hepatocyte IFN response partially rescued the levels of HBV parameters. We observed less HBV RNA synthesis upon HDV infection or HDV protein expression. Additionally, HDV infection or expression of HDAg alone specifically accelerated the decay of HBV RNA, and HDAg was associated with HBV RNAs. On the contrary, HDAg expression did not affect other viruses such as HCV or SARS-CoV-2. CONCLUSIONS: Our data indicate that HDV interferes with HBV through both IFN-dependent and IFN-independent mechanisms. Specifically, we uncover a new viral interference mechanism in which proteins of a satellite virus affect the RNA production of its helper virus. Exploiting these findings could pave the way to the development of new therapeutic strategies against HBV. IMPACT AND IMPLICATIONS: Although the molecular mechanisms remained unexplored, it has long been known that despite its dependency, HDV decreases HBV viremia in patients. Herein, using in vitro and in vivo models, we showed that HDV interferes with HBV through both IFN-dependent and IFN-independent mechanisms affecting HBV RNA metabolism, and we defined the HDV-induced modulation signature. The mechanisms we uncovered could pave the way for the development of new therapeutic strategies against HBV by mimicking and/or increasing the effect of HDAg on HBV RNA. Additionally, the HDV-induced modulation signature could potentially be correlated with responsiveness to IFN-α treatment, thereby helping to guide management of HBV/HDV-coinfected patients.

Does the type of pushing at delivery influence pelvic floor function at 2 months postpartum? A pragmatic randomized trial-The EOLE study.

INTRODUCTION: Maternal pushing techniques during the second stage of labor may affect women's pelvic floor function. Our main objective was to assess the impact of the type of pushing used at delivery on the mother's medium-term pelvic floor function. MATERIAL AND METHODS: This is a secondary analysis of a randomized clinical trial (clinicaltrials.gov: NCT02474745) that took place in four French hospitals from 2015 through 2017 (n = 250). Women in labor with a singleton fetus in cephalic presentation at term who had undergone standardized training in both of these types of pushing were randomized after cervical dilation ≥7 cm. The exclusion criteria were a previous cesarean, a cesarean delivery in this pregnancy or a fetal heart rate anomaly. In the intervention group, open-glottis (OG) pushing was defined as a prolonged exhalation contracting the abdominal muscles to help move the fetus down the birth canal. Closed-glottis (CG) pushing was defined as Valsalva pushing. The principal outcome was the stage of pelvic organ prolapse (POP) assessed by the Pelvic Organ Prolapse-Quantification 2 months after delivery. A secondary outcome was incidence of urinary incontinence (UI). The results of our multivariable, modified intention-to-treat analysis are reported as crude relative risks (RRs) with their 95% confidence intervals. RESULTS: Our analysis included 207 women. Mode of birth was similar in both groups. The two groups did not differ for stage II POP: 10 of 104 (9.4%) in the OG group compared with 7 of 98 (7.1%) in the CG group, for a RR 1.32, 95% confidence interval [CI] 0.52-3.33, and an adjusted RR of 1.22, 95% CI 0.42-3.6. Similarly, the incidence of UI did not differ: 26.7% in the OG group and 28.6% in the CG group (aRR 0.81, 95% CI 0.42-1.53). Subgroup analysis suggests that for secundiparous and multiparous women, OG pushing could have a protective effect on the occurrence of UI (RR 0.33, 95% CI 0.13-0.80). CONCLUSIONS: The type of directed pushing used at delivery did not impact the occurrence of pelvic organ prolapse 2 months after delivery. OG pushing may have a protective effect against UI among secundiparous and multiparous women.

Clinical practice recommendations for nurse-administered intramuscular injections in mental health: A modified Delphi study.

AIM: To develop clinical practice recommendations for nurse-administered intramuscular injections in mental health. BACKGROUND: Intramuscular injection is the main route of long-acting injectable antipsychotics' administration that appear to improve the long-term prognosis of mental illness. Specific guidelines related to the nurse administration of intramuscular injections need to be updated and to explore not only the technical aspects of this procedure. DESIGN: A modified RAND/University of California Los Angeles (UCLA) appropriateness method Delphi study was conducted between October 2019 and September 2020. METHODS: A multidisciplinary steering committee conducted a literature review and developed a list of 96 recommendations. These recommendations were submitted in a two-round Delphi electronic survey to a panel of 49 experienced practicing nurses from five mental health hospitals in France. Each recommendation was rated for its appropriateness and applicability in clinical practice on a 9-point Likert scale. Consensus among nurses was evaluated. The steering committee discussed the results after each round and approved the final set of recommendations. RESULTS: A final set of 79 specific recommendations were accepted for their appropriateness and applicability in clinical practice. Recommendations were classified in five domains: legal and quality assurance aspects, nurse-patient relationship, hygiene, pharmacology, and injection technique. CONCLUSION: The established recommendations placed patients at the heart of the decisions concerning the intramuscular injection and underlined the need for specific training programs. Future research should focus on the integration of these recommendations in clinical practice, by both before-and-after studies and regular assessments of professional practices with relevant indicators. IMPACT: The recommendations developed for good nursing practices explored not only the technical aspects but integrated the nurse-patient relationship. These recommendations may impact usual practices of administration of long-acting injectable antipsychotics and most of them could be applied in many countries. NO PATIENT OR PUBLIC CONTRIBUTION: Due to the study design.

Atypical variants in COL1A1 and COL3A1 associated with classical and vascular Ehlers-Danlos syndrome overlap phenotypes: expanding the clinical phenotype based on additional case reports.

The vast majority of reported (likely) pathogenic missense variants in the genes coding for the fibrillar collagens leads to the substitution of one of the obligatory glycine residues in the Gly-Xaa-Yaa repeat sequence of the triple helical domain. Their phenotypic consequences and deleterious effects have been well-documented. However, with increasing access to molecular diagnostic testing based on next-generation sequencing techniques, such as sequencing of multi-gene panels and whole-exome sequencing, non-glycine substitutions are more frequently identified in individuals suspected to have a heritable collagen disorder, but their pathogenic effect is often difficult to predict.Some specific non-glycine substitutions in the proα1(I)- (p.(Arg312Cys)) and proα1(III)- (glutamic acid to lysine at different positions) collagen chain have been identified in a number of individuals presenting a phenotype showing features of both classical and vascular Ehlers-Danlos syndrome. The number of reported individuals with these defects is currently very low, and several of these non-glycine substitutions had initially been categorised as variants of unknown significance (VUS), complicating early diagnosis, accurate counselling, management guidelines, and correct classification. This collaborative study reports on the phenotype of 22 and 7 individuals harbouring these rare variants in COL1A1 and COL3A1, respectively, expanding our knowledge on clinical presentation, phenotypic variability, and natural history, and informing on the risk for potentially life-threatening events, such as vascular, gastro-intestinal, and pregnancy-related complications.

Immediate consequences and solutions used to maintain medical education during the COVID-19 pandemic for residents and medical students: a restricted review.

BACKGROUND: The COVID-19 outbreak has dramatically impacted medical education, both bedside and academic teaching had to be adapted to comply with the reorganisation of care and social distancing measures. OBJECTIVES: To overview the impact of the pandemic on medical education, including the pedagogical responses adopted and their assessment by medical students and residents. MATERIAL AND METHODS: This restricted systematic review was performed using Rayyan QCRI, to select observational or interventional articles and field experience reports assessing the impact of the COVID-19 pandemic on medical education for medical students and residents. Study design, study population, geographical origin, use of an educational tools (including softwares and social media), their type and assessment, were recorded. For studies evaluating a specific tool the Medical Education Research Study Quality Instrument (MERSQI) was used to assess study quality. RESULTS: The literature search identified 1480 references and 60 articles were selected. Most articles focused on residents (41/60; 69%), and half (30/60; 50%) involved surgical specialties. Online courses were the most frequently used pedagogical tool (52/60; 88%). Simulation tools were used more frequently in articles involving surgical specialties (15/29; 52%) compared with medical specialties (2/14; 12%) (p=0.01). Only four studies reported the assessment of pedagogical tools by medical students, their MERSQI scores ranged from 5.5/18 to 9.0/18. CONCLUSION: Medical education was highly impacted by the COVID-19 pandemic particularly in surgical specialties. Online courses were the most frequently attempted solution to cope with social distancing constraints. Medical students' assessment of pedagogical tools was mostly positive, but the methodological quality of those studies was limited.

Spontaneous Cervical Artery Dissection in Vascular Ehlers-Danlos Syndrome: A Cohort Study.

BACKGROUND AND PURPOSE: Vascular Ehlers-Danlos syndrome is a rare inherited connective tissue disorder because of pathogenic variants in the COL3A1 gene. Arterial complications can affect all anatomic areas and about 25% involve supra-aortic trunks (SATs) but no systematic assessment of cervical artery lesions has been made. The primary objective was to determine an accurate prevalence of spontaneous SAT lesions in a large series of patients with vascular Ehlers-Danlos syndrome at diagnosis and during follow-up. Secondary objectives were to study their neurological consequences (transient ischemic attack or stroke) and the possible relationships with sex, genotype, ascertainment status. METHODS: A retrospective review of a monocentric cohort of patients with molecularly proven vascular Ehlers-Danlos syndrome followed in a tertiary referral center from 2000 to 2017. RESULTS: One hundred forty-four patients were analyzed, 56.9% (n=82) had SAT lesions: 64.6% females, 74.4% index-case patients. Most lesions were identified in early arterial assessment (48% at first work-up, mean age of 35.7±13.0 years). Cumulative incidence of a first identification of a SAT lesion was 41.7% at 40 years old. On the complete period of survey, 183 SAT lesions (with 132 dissections and 33 aneurysms) were identified, mainly in internal carotid arteries (56.3%) and vertebral arteries (28.9%), more rarely in patients with COL3A1 null mutations (P=0.008). Transient ischemic attack or stroke were reported in n=16 (19.5%) of the 82 patients with SAT lesions without relation with age, sex, treatment, or hypertension. CONCLUSIONS: Cervical artery lesions are frequent and mostly asymptomatic in patients with vascular Ehlers-Danlos syndrome. Local dissections and aneurysms are the most frequent type of lesions, but transient ischemic attack or stroke seem rare.

Periodontal (formerly type VIII) Ehlers-Danlos syndrome: Description of 13 novel cases and expansion of the clinical phenotype.

Periodontal Ehlers-Danlos syndrome (pEDS) is a rare condition caused by pathogenic variants in the C1R and C1S genes, encoding subunits C1r and C1s of the first component of the classical complement pathway. It is characterized by early-onset periodontitis with premature tooth loss, pretibial hyperpigmentation and skin fragility. Rare arterial complications have been reported, but venous insufficiency is rarely described. Here we report 13 novel patients carrying heterozygous pathogenic variants in C1R and C1S including three novel C1S variants (c.962G > C, c.961 T > G and c.961 T > A). In addition to the pEDS phenotype, three patients and one relative displayed widespread venous insufficiency leading to persistent varicose leg ulcers. One patient suffered an intracranial aneurysm with familial vascular complications including thoracic and abdominal aortic aneurysm and dissection and intracranial aneurysm rupture. This work confirms that vascular complications can occur, although they are not frequent, which leads us to propose to carry out a first complete non-invasive vascular evaluation at the time of the diagnosis in pEDS patients. However, larger case series are needed to improve our understanding of the link between complement pathway activation and connective tissue alterations observed in these patients, and to better assess the frequency, type and consequences of the vascular complications.

Vascular Ehlers-Danlos syndrome (vEDS): CT and histologic findings of pleural and lung parenchymal damage.

OBJECTIVES: To describe CT features of lung involvement in patients with vascular Ehlers-Danlos syndrome (vEDS), a rare genetic condition caused by pathogenic variants within the COL3A1 gene, characterized by recurrent arterial, digestive, and pulmonary events. MATERIAL AND METHODS: All consecutive vEDS patients referred to the national tertiary referral center for vEDS, between 2004 and 2016, were included. Chest CT scans obtained during the initial vascular work-up were reviewed retrospectively by two chest radiologists for lung involvement. Five surgical samples underwent histologic examination. RESULTS: Among 136 enrolled patients (83 women, 53 men; mean age 37 years) with molecularly confirmed vEDS, 24 (17.6%) had a history of respiratory events: 17 with pneumothorax, 4 with hemothorax, and 3 with hemoptysis that required thoracic surgery in 11. CT scans detected lung parenchymal abnormalities in 78 (57.3%) patients: emphysema (mostly centrilobular and paraseptal) in 44 (32.3%), comparable for smokers and non-smokers; clusters of calcified small pulmonary nodules in 9 (6.6%); and cavitated nodules in 4 (2.9%). Histologic examination of surgical samples found arterial abnormalities, emphysema with alveolar ruptures in 3, accompanied by diffuse hemorrhage and increased hemosiderin resorption. CONCLUSION: In vEDS patients, identification of lung parenchymal abnormalities is common on CT. The most frequently observed CT finding was emphysema suggesting alveolar wall rupture which might facilitate the diagnostic screening of the disease in asymptomatic carriers of a genetic COL3A1 gene mutation. The prognostic value and evolution of these parenchymal abnormalities remain to be evaluated. KEY POINTS: • Patients with vEDS can have lung parenchymal changes on top of or next to thoracal vascular abnormalities and that these changes can be present in asymptomatic cases. • The presence of these parenchymal changes is associated with a slightly higher incidence of respiratory events (although not statistically significant). • Identification of the described CT pattern by radiologists and chest physicians may facilitate diagnostic screening.

Validation of the French Women Abuse Screening Tool to routinely identify intimate partner violence.

BACKGROUND: Health care professionals strongly underestimate the prevalence of intimate partner violence (IPV), and a few of them think that they screen and refer victims appropriately for assistance. The aim of this study was to cross-culturally validate a French version of the Woman Abuse Screening Tool (WAST). METHODS: A multicenter case-control study was performed in the forensic medicine unit of the University Hospital and two offices of the women's rights association in France. Abused and non-abused women self-completed the WAST and a questionnaire assessing their level of comfort in responding to the WAST during the study and during a hypothetical consultation with a physician in primary care. We analyzed the psychometric properties and screening performance of the WAST. RESULTS: Respondent acceptability was very good, with response rates exceeding 95%. The WAST had a good internal consistency (Cronbach α coefficient = 0.95). Its screening performance with a cut-off score of 5 was excellent: area under the ROC curve was 0.99, sensitivity 97.7%, specificity 97.1%, positive predictive value 97.2% and negative predictive value 97.7%. The levels of comfort were significantly lower among abused compared with non-abused women. Both groups of women were more comfortable answering the WAST during the study than in a hypothetical consultation. CONCLUSION: The French version of the WAST was found to be a well-accepted and valid screening tool for routine use in IPV. It may help health care professionals to detect women experiencing abuse early and to refer them more quickly to specific assistance.

Biallelic B3GALT6 mutations cause spondylodysplastic Ehlers-Danlos syndrome.

Proteoglycans are among the most abundant and structurally complex biomacromolecules and play critical roles in connective tissues. They are composed of a core protein onto which glycosaminoglycan (GAG) side chains are attached via a linker region. Biallelic mutations in B3GALT6, encoding one of the linker region glycosyltransferases, are known to cause either spondyloepimetaphyseal dysplasia (SEMD) or a severe pleiotropic form of Ehlers-Danlos syndromes (EDS). This study provides clinical, molecular and biochemical data on 12 patients with biallelic B3GALT6 mutations. Notably, all patients have features of both EDS and SEMD. In addition, some patients have severe and potential life-threatening complications such as aortic dilatation and aneurysm, cervical spine instability and respiratory insufficiency. Whole-exome sequencing, next generation panel sequencing and direct sequencing identified biallelic B3GALT6 mutations in all patients. We show that these mutations reduce the amount of ß3GalT6 protein and lead to a complete loss of galactosyltransferase activity. In turn, this leads to deficient GAG synthesis, and ultrastructural abnormalities in collagen fibril organization. In conclusion, this study redefines the phenotype associated with B3GALT6 mutations on the basis of clinical, molecular and biochemical data in 12 patients, and provides an in-depth assessment of ß3GalT6 activity and GAG synthesis to better understand this rare condition.

Classical Ehlers-Danlos syndrome with a propensity to arterial events: A new report on a French family with a COL1A1 p.(Arg312Cys) variant.

Ehlers-Danlos syndromes (EDS) are a clinically and genetically heterogeneous group of connective tissue disorders. Overlapping features including arterial aneurysms/dissections in both classical and vascular EDS are a major challenge in the clinical diagnosis of these subtypes. The COL1A1 p.(Arg312Cys) variant leads to a phenotype of classical EDS with a propensity to arterial complications. Our report describes a two-generation family with one individual presenting with a dissection of the right external iliac artery. The primary suspicion of vascular EDS with the unsatisfactory identification of a COL3A1 benign variant was secondarily readjusted with the identification of COL1A1 p.(Arg312Cys) variant. This raises the question of the association of COL1A1 p.(Arg312Cys) with arterial complications and the need for a gene panel including not only the usual genes tested in search of classical or vascular EDS but also COL1A1.

Communication of genetic information to at-risk relatives during the multidisciplinary monitoring of vascular Ehlers-Danlos syndrome in a French referral clinic.

Vascular Ehlers-Danlos syndrome (vEDS) is a rare inherited disorder leading to arterial, digestive, and uterine complications due to pathogenic COL3A1 variants. Identification of causal variants allows family screening, provided that relatives have previously been informed, according to a 2013 French Decree. The aims of our study were to assess the communication of genetic information to at-risk relatives, the impact of diagnosis disclosure and to highlight a possible link between the experience of vEDS patients and ability to communicate about genetic information. A total of n = 51 vEDS adult probands answered a questionnaire during a clinical visit. Communication to relatives was considered effective if the proband gave information to some or all first-degree relatives and considered easily achieved if it was disclosed to all relatives less than a month after the diagnosis and without difficulty. Personal and family vEDS experiences of probands were also assessed. Effective communication of information to relatives was remarkably high (98%). Siblings were the most frequently informed relatives (82%). Women informed their at-risk relatives of genetic family screening faster (p = .006) and easier (p = .004) than men. There was no difference in the disclosure of information to relatives before and after 2013 in our multidisciplinary clinic. Regarding the lived experience of vEDS patients, they felt anxious (78%) at diagnosis disclosure but also considered this diagnosis as an opportunity to start a medical follow-up (82%) putting an end to diagnosis delay. Our findings highlight for the first time that the ability to easily inform at-risk first-degree relatives is related to the relief felt during vEDS-positive diagnosis disclosure (p = .04). In order to improve the communication of genetic information to relatives, we believe that psychological support should systematically be part of the multidisciplinary monitoring, just as medical follow-up and genetic counseling.

Frequency of de novo variants and parental mosaicism in vascular Ehlers-Danlos syndrome.

PURPOSE: Vascular Ehlers-Danlos syndrome (vEDS) is a rare inherited autosomal dominant disorder caused by COL3A1 pathogenic variants. A high percentage of de novo cases has been suggested. Part of it could be due to parental mosaicism, but its frequency is unknown. METHODS: This retrospective study included a large series of COL3A1-confirmed vEDS probands with family information. The frequency of de novo cases was evaluated and the distribution of the type of variants was compared according to the mode of inheritance. The COL3A1 mosaicism was studied by deep targeted next- generation sequencing (NGS) from parental blood DNA. RESULTS: Out of 177 vEDS probands, 90 had a negative family history, suggesting a high rate (50.8%) of de novo pathogenic variants, enriched in the more severe COL3A1 variants (no null variant). Among those, both parental DNA were available in 36 cases and one parental DNA in 18 cases. NGS detected only one mosaicism from maternal blood DNA (allelic ratio 18%), which was confirmed in saliva (allelic ratio 22%). CONCLUSION: vEDS is characterized by a high frequency of de novo pathogenic variants. Parental mosaicism is rare (2-3%), but should be systematically searched with targeted NGS, taking into account its importance in genetic counseling.

Atypical COL3A1 variants (glutamic acid to lysine) cause vascular Ehlers-Danlos syndrome with a consistent phenotype of tissue fragility and skin hyperextensibility.

PURPOSE: The Ehlers-Danlos syndromes (EDS) are a group of rare inherited connective tissue disorders. Vascular EDS (vEDS) is caused by pathogenic variants in COL3A1, most frequently glycine substitutions. We describe the phenotype of the largest series of vEDS patients with glutamic acid to lysine substitutions (Glu>Lys) in COL3A1, which were all previously considered to be variants of unknown significance. METHODS: Clinical and molecular data for seven families with three different Glu>Lys substitutions in COL3A1 were analyzed. RESULTS: These Glu>Lys variants were reclassified from variants of unknown significance to either pathogenic or likely pathogenic in accordance with American College of Medical Genetics and Genomics guidelines. All individuals with these atypical variants exhibited skin hyperextensibility as seen in individuals with classical EDS and classical-like EDS and evidence of tissue fragility as seen in individuals with vEDS. CONCLUSION: The clinical data demonstrate the overlap between the different EDS subtypes and underline the importance of next-generation sequencing gene panel analysis. The three different Glu>Lys variants point toward a new variant type in COL3A1 causative of vEDS, which has consistent clinical features. This is important knowledge for COL3A1 variant interpretation. Further follow-up data are required to establish the severity of tissue fragility complications compared with patients with other recognized molecular causes of vEDS.

Correction: Arterial tortuosity syndrome: 40 new families and literature review.

In the published version of this paper the author Neus Baena's name was incorrectly given as Neus Baena Diez. This has now been corrected in both the HTML and PDF versions of the paper.

Pseudoxanthoma elasticum with prominent arterial calcifications evoking CD73 deficiency.

Pseudoxanthoma elasticum (PXE) is a rare disorder characterized by skin, eye, and cardiovascular lesions due to ectopic mineralization and fragmentation of elastic fibers of connective tissues. We present an atypical case of PXE with diffuse vascular calcification and negligible skin and eye lesions. The patient was a 37-year-old man suffering from severe bilateral arterial calcifications in superficial femoral and posterior tibial arteries. Eye fundoscopy and skin examination were first considered normal. This phenotype suggested first the diagnosis of Arterial Calcification due to Deficiency of CD73 (ACDC) characterized by mutations in NT5E gene. However, we found two variants in ABCC6 gene, and no variant in NT5E. Skin reexamination revealed few lateral skin papules confined to the scalp. Phenotypic overlap was described in vascular calcification disorders, between GACI and PXE phenotypes, and we discuss here expansion of this overlap, including ACDC phenotype. Identification of these expanding and overlapping phenotypes was enabled by genetic screening of the corresponding genes, in a systematic approach. We propose to create a calcification next generation sequencing (NGS) panel with NT5E, GGCX, ENPP1, and ABCC6 genes to improve the molecular diagnosis of vascular calcification.

Nurses' practices in the preparation and administration of intramuscular injections in mental health: A cross-sectional study.

BACKGROUND: Intramuscular injections (IMIs) remain a frequent practice in mental health. Few studies have examined the issue of nurses' practices concerning IMI in this domain, and none considered specifically hygiene. Finally, no study appears to have looked at emergency situations and their possible influence on practices. The principal objective of our study was to assess the practices associated with IMI in mental health, especially the hygiene-related practices. The secondary objectives were as follows: 1) to assess the practices for the preparation and administration of IMI in mental health for criteria other than hygiene and 2) to determine whether professional experience and emergency situations influence these practices. DESIGN: Single-centre cross-sectional study in a psychiatric Hospital and adherence to the STROBE guidelines. METHODS: The participating nurses all worked with inpatients, and all volunteered for the study. A self-administered questionnaire was sent to all participants. The questionnaire included questions about knowledge and practices associated with IMI, some considered in two different situations: emergencies and planned injections. The distribution of the responses was tested by the chi-squared test or Fisher's exact test, as appropriate, or by McNemar's chi-squared test or Friedman's nonparametric chi-squared test for matched data. RESULTS: Response rate was 48.6%. Overall, 81% of nurses reported correct handwashing before preparation, 87.5% responded that the dorsogluteal site is currently recommended for IMI, and 74.6% that they did not know the "Z track" technique. In planned injections, 58.7% reported that the choice of needle was determined, at least in part, by the patient's body mass index. In emergency situations, adherence to guidelines was less frequent for all types of practices. CONCLUSIONS: This study shows the need to improve practices for the frequently used procedure of IMI among mental health nurses. RELEVANCE TO CLINICAL PRACTICE: Better professional education appears necessary to develop optimal practices, especially in emergency situations.

Simultaneous sequencing of 37 genes identified causative mutations in the majority of children with renal tubulopathies.

The clinical diagnosis of inherited renal tubulopathies can be challenging as they are rare and characterized by significant phenotypic variability. Advances in sequencing technologies facilitate the establishment of a molecular diagnosis. Therefore, we determined the diagnostic yield of a next generation sequencing panel assessing relevant disease genes in children followed through three national networks with a clinical diagnosis of a renal tubulopathy. DNA was amplified with a kit provided by the European Consortium for High-Throughput Research in Rare Kidney Diseases with nine multiplex PCR reactions. This kit produced 571 amplicons covering 37 genes associated with tubulopathies followed by massive parallel sequencing and bioinformatic interpretation. Identified mutations were confirmed by Sanger sequencing. Overall, 384 index patients and 16 siblings were assessed. Most common clinical diagnoses were 174 patients with Bartter/Gitelman syndrome and 76 with distal renal tubular acidosis. A total of 269 different variants were identified in 27 genes, of which 95 variants were considered likely, 136 definitely pathogenic and 100 had not been described at annotation. These mutations established a genetic diagnosis in 245 of the index patients. Genetic testing changed the clinical diagnosis in 16 cases and provided insights into the phenotypic spectrum of the respective disorders. Our results demonstrate a high diagnostic yield of genetic testing in children with a clinical diagnosis of a renal tubulopathy, consistent with a predominantly genetic etiology in known disease genes. Thus, genetic testing helped establish a definitive diagnosis in almost two-thirds of patients thereby informing prognosis, management and genetic counseling.

Arterial tortuosity syndrome: 40 new families and literature review.

PURPOSE: We delineate the clinical spectrum and describe the histology in arterial tortuosity syndrome (ATS), a rare connective tissue disorder characterized by tortuosity of the large and medium-sized arteries, caused by mutations in SLC2A10. METHODS: We retrospectively characterized 40 novel ATS families (50 patients) and reviewed the 52 previously reported patients. We performed histology and electron microscopy (EM) on skin and vascular biopsies and evaluated TGF-ß signaling with immunohistochemistry for pSMAD2 and CTGF. RESULTS: Stenoses, tortuosity, and aneurysm formation are widespread occurrences. Severe but rare vascular complications include early and aggressive aortic root aneurysms, neonatal intracranial bleeding, ischemic stroke, and gastric perforation. Thus far, no reports unequivocally document vascular dissections or ruptures. Of note, diaphragmatic hernia and infant respiratory distress syndrome (IRDS) are frequently observed. Skin and vascular biopsies show fragmented elastic fibers (EF) and increased collagen deposition. EM of skin EF shows a fragmented elastin core and a peripheral mantle of microfibrils of random directionality. Skin and end-stage diseased vascular tissue do not indicate increased TGF-ß signaling. CONCLUSION: Our findings warrant attention for IRDS and diaphragmatic hernia, close monitoring of the aortic root early in life, and extensive vascular imaging afterwards. EM on skin biopsies shows disease-specific abnormalities.