Efficacy and safety of SENS-401 in sudden sensorineural hearing loss: The AUDIBLE-S randomized placebo-controlled phase IIb trial.

PURPOSE: Safety and efficacy of SENS-401, a serotonin type 3 (5-HT3) receptor antagonist and calcineurin inhibitor, in patients with acute sudden sensorineural hearing loss (SSNHL). METHODS: Multicentre randomized, double blind, placebo-controlled trial enrolled adult subjects with sudden sensorineural hearing loss (SSNHL) or unilateral/bilateral acute acoustic trauma leading to SSNHL within 96 h of disease onset. Subjects were randomly assigned to one of the three oral dose groups: 29 mg, 43.5 mg or placebo given twice daily for 28 days. The primary endpoint was the change from baseline in Pure Tone Average (PTA) in the affected ear to the end of treatment visit (day 28). Subjects were further followed up 8 weeks after the end of the treatment period (day 84). RESULTS: A total of 115 subjects were randomized. SENS-401 was well tolerated. Although the primary efficacy endpoint was not met at day 28, post-hoc analyses revealed clinically significant and meaningful efficacy outcomes with SENS-401 when compared to placebo in a substantial group of participants diagnosed with idiopathic SSNHL and who had received corticosteroid treatment. Notable improvements were observed in the PTA change from baseline, the complete hearing recovery rate, and the Word Recognition Score (WRS), particularly at day 84. The responder rate consistently favored treated subjects over those who received the placebo. CONCLUSION: While the primary endpoint was not achieved at the end of the treatment period, the study revealed consistently positive efficacy results of clinical relevance in patients with idiopathic SSNHL who received SENS-401, particularly in the 8-weeks follow-up phase after the completion of the treatment.

Plant extracts, polymers and new approach methods: Practical experience with skin sensitization assessment.

Over the last decade, research into methodologies to identify skin sensitization hazards has led to the adoption of several non-animal methods as OECD test guidelines. However, predictive accuracy beyond the chemical domains of the individual validation studies remains largely untested. In the present study, skin sensitization test results from in vitro and in chemico methods for 12 plant extracts and 15 polymeric materials are reported and compared to available in vivo skin sensitization data. Eight plant extracts were tested in the DPRA and h-CLAT, with the 2 out of 3 approach resulting in a balanced accuracy of 50%. The balanced accuracy for the 11 plant extracts assessed in the SENS-IS was 88%. Excluding 5 polymers inconclusive in vitro, the remainder, assessed using the 2 out of 3 approach, resulted in 63% balanced accuracy. The SENS-IS method, excluding one polymeric material due to technical inapplicability, showed 68% balanced accuracy. Although based on limited numbers, the results presented here indicate that some substance subgroups may not be in the applicability domains of the method used and careful analysis is required before positive or negative results can be accepted.

Measurement of quality of life in orthognathic surgery using an original questionnaire: About a series of 123 cases.

INTRODUCTION: The aim of this study was to measure changes in the quality of life of patients who had orthognathic surgery using an original questionnaire, designed for this purpose. MATERIAL AND METHOD: This single-center retrospective study included all patients who had orthognathic surgery in our center between 2014 and 2019. An original questionnaire comprising 13 items in 4 domains was sent to patients postoperatively by email after telephone contact and obtaining their consent. Items were scored on a 5-point scale ranging from (-1), worse than before surgery, to (+3), better than before surgery. RESULTS: All data were collected in a standardized way. In total, 123 patients responded. The mean score for all surgeries combined was +1.14, indicating an improvement in QOL considered to be "low to moderate". A total of 118 patients (95.9%) reported an improvement following surgery, including 18 patients (14.6%) who reported a marked improvement. The greatest improvement was observed for psychosocial aspects and morphology. CONCLUSION: This study shows a positive effect of orthognathic surgery on patients' QOL, including self-perception, relationships with others, or functional aspects as mastication and breathing. We propose an original tool that is easy to use by patients to measure quality of life following orthognathic surgery.

[Thadeo, a listening service for caregivers]. / Thadeo, un service d'écoute pour les soignants.

Caregivers, like all working people, can encounter difficulties in the course of their professional activities. These difficulties, compounded by the particularities of caregiving practice, can lead to situations of isolation, overwork, exhaustion, disagreement and even ethical dilemmas in complex situations. Thadeo's free listening service offers support to caregivers who need it.

Criterion Validity of Linear Accelerations Measured with Low-Sampling-Frequency Accelerometers during Overground Walking in Elderly Patients with Knee Osteoarthritis.

Sensors with a higher sampling rate produce higher-quality data. However, for more extended periods of data acquisition, as in the continuous monitoring of patients, the handling of the generated big data becomes increasingly complicated. This study aimed to determine the validity and reliability of low-sampling-frequency accelerometer (SENS) measurements in patients with knee osteoarthritis. Data were collected simultaneously using SENS and a previously validated sensor (Xsens) during two repetitions of overground walking. The processed acceleration signals were compared with respect to different coordinate axes to determine the test-retest reliability and the agreement between the two systems in the time and frequency domains. In total, 44 participants were included. With respect to different axes, the interclass correlation coefficient for the repeatability of SENS measurements was [0.93-0.96]. The concordance correlation coefficients for the two systems' agreement were [0.81-0.91] in the time domain and [0.43-0.99] in the frequency domain. The absolute biases estimated by the Bland-Altman method were [0.0005-0.008] in the time domain and [0-0.008] in the frequency domain. Low-sampling-frequency accelerometers can provide relatively valid data for measuring the gait accelerations in patients with knee osteoarthritis and can be used in the future for remote patient monitoring.

[Choosing to be a psychiatric nurse]. / Choisir d'être infirmier en psychiatrie.

Being a nurse in psychiatry is not an accident. The particularity of the care and people being cared for and the autonomy of the nurse in his or her role as clinician can guide the choice to practice this profession in this environment. Similarly, the particularities of the technical care provided in psychiatry and the special place of the care teams are also arguments to explain this decision.

Comparative study of i-SENS glucometers in neonates using capillary blood samples.

OBJECTIVES: The accuracy of point-of-care blood glucometers in the detection and evaluation of neonatal hypoglycemia is a concern. This study compared the performance of three i-SENS glucometers with that of the YSI 2300 STAT Plus Analyzer, which was used as a reference. METHODS: The leftover neonatal capillary blood samples of 319 patients were used in this study. The evaluation process and accuracy performance criteria were based on the International Organization for Standardization 15197:2013 guidelines. The evaluation involved three i-SENS glucometers (BAROzen H Expert plus, CareSens PRO, and CareSens H Beat) and the ACCU-CHEK® Inform II glucometer. RESULTS: The accuracy evaluation yielded acceptable results as follows: a) 100 and 100% for BAROzen H Expert plus; 99.8 and 100% for CareSens PRO; 98.7%, and 97.2% for CareSens H Beat glucometers were within the range of ±0.8 mmol/L (15 mg/dL) and ±15% of the average reference values at glucose concentrations <5.55 mmol/L (100 mg/dL) and ≥5.55 mmol/L (100 mg/dL), respectively, and b) all estimated glucose values (100%) were within the zones A and B of Consensus Error Grid for all three i-SENS glucometers. There was good correlation between the glucose values estimated by the glucometers and the reference values (R>0.990). CONCLUSIONS: This study demonstrated that i-SENS glucometers exhibit acceptable performance and can be used as effective point-of-care devices in neonates.

Performance of ivisen IA-1400, a new point-of-care device with an internal centrifuge system, for the measurement of cardiac troponin I levels.

BACKGROUND: We present the analytical performance of the ivisen IA-1400, a new point-of-care device that features a characteristic built-in centrifuge system, to measure blood cardiac troponin I (cTnI) levels. METHODS: Whole blood and plasma samples obtained from patients who visited Korea University Guro Hospital were used to analyze measurement range, cross-reactivity, interference, and sensitivity and specificity. We performed a correlation analysis of the ivisen IA-1400 versus the Access AccuTnI+3 immunoassay using the UniCel™ DxI 800 platform and the PATHFAST™ hs-cTnI assay. RESULTS: Within-run precisions were classified as low, 9.8%; middle, 10.2%; and high, 8.5%. The limit of blank was 3.1 ng/L for plasma samples and 4.3 ng/L for whole blood samples. The limit of detection was 8.4 ng/L for plasma samples and 10.0 ng/L for whole blood samples, respectively. The limit of quantitation at a coefficient of variation of 20% and 10% was 19.5 ng/L and 45.5 ng/L for plasma samples, respectively. The comparative evaluation between the two other assays and ivisen IA-1400 showed excellent correlation, with Spearman's correlation coefficients (R) of 0.992 and 0.985. The sensitivity and specificity of ivisen IA-1400 using the optimum cut-off value of 235 ug/L were 94.6% and 98.2%, respectively. CONCLUSION: The ivisen IA-1400 showed acceptable and promising performance in cTnI measurements using whole blood and plasma samples, with limited information in the clinical performance. The flexibility for sample selection using the internal centrifugation system is the main advantage of this point-of-care device.

[Olfactory workshops to renew the links between scents and memory]. / Des ateliers olfactifs pour renouer les liens entre senteurs et mémoire.

Smells and memories are closely linked with a particular emotional status. Most smells are imprinted in our memory from childhood. Based on this observation, a professional from the perfume industry has created olfactory workshops for residents of retirement homes. The workshops focus on well-being and the cognitive perception of odours. Testimonial.

Performance evaluation of three i-SENS glucometers using arterial blood samples compared with the YSI 2300 Glucose Analyzer.

BACKGROUND: Capillary blood is the most commonly used sample for point-of-care (POC) glucometers. However, in critically ill patients, the glucose levels measured from capillary blood may not be reliable. Thus, we aimed to evaluate and compare the accuracy of glucose levels measured with POC glucometers and the YSI 2300 glucose analyzer using leftover arterial blood samples. METHODS: In total, 100 leftover heparinized arterial blood samples were used to evaluate the performance of three i-SENS glucometers (BAROzen H Expert plus, CareSens PRO, and CareSens H Beat) and the ACCU-CHEK® Inform II glucometer. The reference value was obtained using the YSI 2300 glucose analyzer. The results were analyzed based on International Organization for Standardization 15197:2013 guidelines. RESULTS: More than 95% of results obtained using POC glucometers were within ±15 mg/dL of the reference value for glucose concentrations <100 mg/dL and within ±15% of the reference value for glucose concentrations ≥100 mg/dL. In the consensus error grid analysis, more than 99% of results were found to be within zones A and B. An excellent correlation was found between the values obtained using POC glucometers and the YSI 2300 glucose analyzer (R2  > .99). CONCLUSION: The i-SENS glucometers showed stable and accurate results when leftover arterial blood samples were used. Therefore, POC glucometers could be useful in critical care settings, such as intensive care units, where arterial samples are routinely used.

The basophil activation test differentiates between patients with alpha-gal syndrome and asymptomatic alpha-gal sensitization.

BACKGROUND: Galactose-alpha-1,3-galactose (alpha-gal) syndrome is characterized by the presence of serum specific IgE antibodies to alpha-gal and delayed type I allergic reactions to the carbohydrate alpha-gal after consumption of mammalian (red) meat products and drugs of mammalian origin. Diagnostics currently rely on patient history, skin tests, determination of serum specific IgE antibodies, and oral food or drug challenges. OBJECTIVE: We sought to assess the utility of different basophil parameters (basophil reactivity and sensitivity, the ratio of the percentage of CD63+ basophils induced by the alpha-gal-containing allergen to the percentage of CD63+ basophils after stimulation with anti-FcεRI antibody [%CD63+/anti-FcεRI], and area under the dose-response curve [AUC]) as biomarkers for the clinical outcome of patients with alpha-gal syndrome compared with subjects with asymptomatic alpha-gal sensitization. METHODS: In addition to routine diagnostics, a basophil activation test (Flow CAST) with different concentrations of alpha-gal-containing allergens (eg, commercially available alpha-gal-carrying proteins and pork kidney extracts) was performed in 21 patients with alpha-gal syndrome, 12 alpha-gal-sensitized subjects, and 18 control subjects. RESULTS: Alpha-gal-containing allergens induced strong basophil activation in a dose-dependent manner in patients. Basophil reactivity at distinct allergen concentrations, the %CD63+/anti-FcεRI ratio across most allergen concentrations, the AUC of dose-response curves, and basophil allergen threshold sensitivity (CD-sens) with pork kidney extract were significantly higher in patients with alpha-gal syndrome compared with those in sensitized subjects. All parameters were negative in control subjects. CONCLUSION: The basophil activation test should be considered as an additional diagnostic test before performing time-consuming and potentially risky oral provocation tests. The %CD63+/anti-FcεRI ratio for all allergens and AUCs for pork kidney were the best parameters for distinguishing patients with alpha-gal syndrome from subjects with asymptomatic alpha-gal sensitization.

[Touch, an occupational therapy approach to the elderly person]. / Le toucher, une approche en ergothérapie de la personne âgée.

The hand, a vector of knowledge and understanding of the surrounding world, promotes relationships. For all medico-social professionals, taking care of the hand involves touch, benevolent accompaniment to encourage movement and involvement in the activities of daily life. Touch in the relationship with the elderly person places the occupational therapist in the dynamics of rehabilitation in an interprofessional team. Three facets of touch are described.

[Modernity and turmoil of adolescence]. / Modernité et désarrois de l'adolescence.

Teenagers sometimes show us, in quite dramatic fashion, the upheavals they face as they embark on the difficult journey towards adulthood. Removed from parental directions and ideals, they need to follow their own subjective compass, in a social relationship where anxiety is ever present. Far from being indifferent to the world, they offer a lucid insight into its flaws and false pretences, in a distraught search for meaning. In this state of vulnerability and internal disarray, they can be exposed to the risk of fanaticism and deadly beliefs which promise a resolution to the chaos of their existence. The use of screens as a place to hide behind, segregational communities, toxic pathways, like an artificial veil on the world, are all dangerous solutions to which the teenager may turn.

[Meaning of life and mental health: the role of religion]. / Sens de la vie et santé mentale : le rôle de la religion.

Patients suffering from severemental illness often turn to spirituality to help cope with their difficulties, in particular to (re)discover meaning in life.Some thereby try to explain their symptoms through religious causes.Generally, turning to spirituality in this way can be adaptive or on the contrary, detrimental. This question and its therapeutic consequences arediscussed and illustrated through clinical examples.

À la recherche de la vision « normale ¼ : mesurer l'acuité visuelle au XIXe siècle.

This article aims to reconstruct and analyze debates centring on normal eye and vision standards during the second half of the 19th century in Europe. It particularly addresses the creation of ophthalmology charts, one of the main tools for measuring visual acuity. Having briefly described the historical context in which modern eye charts were developed, we will present the better known examples of these and their characteristics. We will then analyze ophthalmologists' debates about what constitutes a normal eye and normal vision, and show the discrepancy between established definitions and clinical studies. Finally, we will consider the issue of measuring eyesight while focusing, on the one hand, on specialists' desire to create a standardized framework to measure visual acuity and, on the other hand, on the multiple hurdles that hindered achieving that goal.

Cet article a pour objectif d'analyser les débats sur les normes définissant l'œil et la vision « normaux ¼ pendant la seconde moitié du XIXe siècle en Europe. Il s'attache en particulier à la création des tableaux ophtalmologiques, l'un des principaux instruments utilisés pour mesurer l'acuité visuelle. Après avoir évoqué le cadre historique dans lequel les tableaux visuels modernes ont été développés, nous présenterons les plus célèbres d'entre eux ainsi que leurs caractéristiques. Nous analyserons ensuite les débats entre ophtalmologistes sur ce que sont une vision ou un œil dits normaux et nous montrerons le décalage entre les définitions théoriques avancées et les résultats des études cliniques. Enfin, nous considérerons la question de la mesure de l'acuité visuelle en dévoilant, d'une part, la volonté des spécialistes d'établir un cadre normatif et, d'autre part, les multiples obstacles qu'ils ont affrontés.

Management of peripheral vertigo with antihistamines: New options on the horizon.

Vertigo is associated with a wide range of vestibular pathologies. It increasingly affects the elderly, with a high cost to society. Solutions include vestibular suppressants and vestibular rehabilitation, which form the mainstay of therapy. Antihistamines represent the largest class of agents used to combat vestibular vertigo symptoms. Agents targeting the H1 and H3 receptors have been in clinical use for several decades as single agents. Nonetheless, effective management of vertigo proves elusive as many treatments largely address only associated symptoms, and with questionable efficacy. Additionally, the primary and limiting side effect of sedation is counterproductive to normal functioning and the natural recovery process occurring via central compensation. To address these issues, the timing of administration of betahistine, the mainstay H3 antihistamine, can be fine-tuned, while bioavailability is also being improved. Other approaches include antihistamine combination studies, devices, physical therapy and behavioural interventions. Recently demonstrated expression of H4 receptors in the peripheral vestibular system represents a new potential drug target for treating vestibular disorders. A number of novel selective H4 antagonists are active in vestibular models in vivo. The preclinical potential of SENS-111 (Seliforant), an oral first-in-class selective H4 antagonist is the only such molecule to date to be translated into the clinical setting. With an excellent safety profile and notable absence of sedation, encouraging outcomes in an induced vertigo model in healthy volunteers have led to ongoing clinical studies in acute unilateral vestibulopathy, with the hope that H4 antagonists will offer new effective therapeutic options to patients suffering from vertigo.

Structural description of surfaces and interfaces in biominerals by DNP SENS.

Biological mineralized tissues are hybrid materials with complex hierarchical architecture composed of biominerals often embedded in an organic matrix. The atomic-scale comprehension of surfaces and organo-mineral interfaces of these biominerals is of paramount importance to understand the ultrastructure, the formation mechanisms as well as the biological functions of the related biomineralized tissue. In this communication we demonstrate the capability of DNP SENS to reveal the fine atomic structure of biominerals, and more specifically their surfaces and interfaces. For this purpose, we studied two key examples belonging to the most significant biominerals family in nature: apatite in bone and aragonite in nacreous shell. As a result, we demonstrate that DNP SENS is a powerful approach for the study of intact biomineralized tissues. Signal enhancement factors are found to be up to 40 and 100, for the organic and the inorganic fractions, respectively, as soon as impregnation time with the radical solution is long enough (between 12 and 24 h) to allow an efficient radical penetration into the calcified tissues. Moreover, ions located at the biomineral surface are readily detected and identified through 31P or 13C HETCOR DNP SENS experiments. Noticeably, we show that protonated anions are preponderant at the biomineral surfaces in the form of HPO42- for bone apatite and HCO32- for nacreous aragonite. Finally, we demonstrate that organo-mineral interactions can be probed at the atomic level with high sensitivity. In particular, reliable 13C-{31P} REDOR experiments are achieved in a few hours, leading to the determination of distances, molar proportion and binding mode of citrate bonded to bone mineral in native compact bone. According to our results, only 80% of the total amount of citrate in bone is directly interacting with bone apatite through two out of three carboxylic groups.

REACH alternative testing strategy for skin sensitization in practice: Fact or fiction?

From October 2016 the REACH Regulation requires an alternative testing strategy for skin sensitization. The current paper describes our experience when putting into practice the REACH alternative testing strategy with a modification for 50 industrial chemicals in total, including mono-constituents, multi-constituents and UVCBs. For mono- and multi-constituents, a tiered approach was followed starting with an in silico (Derek Nexus) assessment, DPRA and KeratinoSens™ assay, followed by a weight of evidence conclusion based on the generated data, or further testing using the U-SENS™ assay. For UVCBs testing started with the KeratinoSens™ assay followed by the U-SENS™ assay if additional relevant information could be gained for an overall conclusion. From the 50 substances tested, for 46% a conclusion on skin sensitization potential and potency could be drawn based on the non-animal testing strategy; however, 54% of the substances still needed to be studied in vivo due to discordant results from non-animal testing or the need for reliable potency data. Important issues with the currently available, validated non-animal methods are the lack or comparability of skin metabolism and lack of potency indication, which is present in the in vivo assays. Skin sensitization testing for UVCBs and multi-constituents is still in a grey area, as neither the in chemico, in vitro assays, and in vivo LLNA have been validated for UVCBs and multi-constituents.

[Vulnerability linked to age and memory disorders]. / Vulnérabilité liée à l'âge et troubles mnésiques.

Violence towards elderly people can be hidden or trivialised. It often results from misunderstandings adding an argumentative edge to the relationship. Its prevention involves respecting elderly people's wishes and acknowledging their efforts and their anxieties and not simply pointing at the inadequacy of the resources available in a practice still too often seen as discriminatory.

[Ageing, a hidden form of violence]. / Vieillir, une violence qui ne dit pas son nom.

Violence towards the elderly can occur in various forms. These include domestic or institutional abuse but other more covert forms exist. The complex conditions of their appearance, both in the elderly victim as well as in their abusers imply a pluridisciplinary repsonse. It is essential to preserve the notions of humanity, the safety of the elderly, autonomy and the respect of the wishes of our senior citizens.