The multinational second Diabetes, Attitudes, Wishes and Needs study: results of the French survey

International audienceAIM:The second Diabetes, Attitudes, Wishes and Needs (DAWN2™) multinational cross-sectional study was aimed at generating insights to facilitate innovative efforts by people with diabetes (PWD), family members (FMs), and health care professionals (HCPs) to improve self-management and psychosocial support in diabetes. Here, the French data from the DAWN2™ study are described.METHODS:In France, 500 PWD (80 with type 1 diabetes [T1] and 420 with type 2 diabetes [T2]), 120 FMs, and 288 HCPs were recruited. The questionnaires assessed the impact of diabetes on quality of life and mood, self-management, attitudes/beliefs, and care/support.RESULTS:Diabetes negatively impacted the emotional well-being of 59% of people with T1 versus 45% of people with T2 (P<0.05) and about half of FMs. A high level of distress was felt by about half of PWD and FMs. About half of HCPs reported assessing depression in their patients. Sixty-two percent of FMs considered managing diabetes to be a burden. Hypoglycemia was a source of concern for 64% of people with T1 and 73% of FMs of insulin users. About two-thirds of non-insulin-medicated people with T2 agreed to start insulin if prescribed, while half of HCPs preferred to delay insulin initiation. A discrepancy between HCPs' perceptions of their interactions with their patients and PWD's recollection of these interactions with regard to patients' personal needs and distress was also observed.CONCLUSION:While distress remains under-assessed by HCPs, the negative impact of diabetes on the lives of PWD and FMs clearly induces distress on both groups. These findings provide new understanding of barriers precluding optimal management of diabetes. Developing strategies to overcome these barriers is now warranted

Ototoxicity: a high risk to auditory function that needs to be monitored in drug development

Hearing loss constitutes a major global health concern impacting approximately 1.5 billion people worldwide. Its incidence is undergoing a substantial surge with some projecting that by 2050, a quarter of the global population will experience varying degrees of hearing deficiency. Environmental factors such as aging, exposure to loud noise, and the intake of ototoxic medications are implicated in the onset of acquired hearing loss. Ototoxicity resulting in inner ear damage is a leading cause of acquired hearing loss worldwide. This could be minimized or avoided by early testing of hearing functions in the preclinical phase of drug development. While the assessment of ototoxicity is well defined for drug candidates in the hearing field – required for drugs that are administered by the otic route and expected to reach the middle or inner ear during clinical use – ototoxicity testing is not required for all other therapeutic areas. Unfortunately, this has resulted in more than 200 ototoxic marketed medications. The aim of this publication is to raise awareness of drug-induced ototoxicity and to formulate some recommendations based on available guidelines and own experience. Ototoxicity testing programs should be adapted to the type of therapy, its indication (targeting the ear or part of other medications classes being potentially ototoxic), and the number of assets to test. For multiple molecules and/or multiple doses, screening options are available: in vitro (otic cell assays), ex vivo (cochlear explant), and in vivo (in zebrafish). In assessing the ototoxicity of a candidate drug, it is good practice to compare its ototoxicity to that of a well-known control drug of a similar class. Screening assays provide a streamlined and rapid method to know whether a drug is generally safe for inner ear structures. Mammalian animal models provide a more detailed characterization of drug ototoxicity, with a possibility to localize and quantify the damage using functional, behavioral, and morphological read-outs. Complementary histological measures are routinely conducted notably to quantify hair cells loss with cochleogram. Ototoxicity studies can be performed in rodents (mice, rats), guinea pigs and large species. However, in undertaking, or at the very least attempting, all preclinical investigations within the same species, is crucial. This encompasses starting with pharmacokinetics and pharmacology efficacy studies and extending through to toxicity studies. In life read-outs include Auditory Brainstem Response (ABR) and Distortion Product OtoAcoustic Emissions (DPOAE) measurements that assess the activity and integrity of sensory cells and the auditory nerve, reflecting sensorineural hearing loss. Accurate, reproducible, and high throughput ABR measures are fundamental to the quality and success of these preclinical trials. As in humans, in vivo otoscopic evaluations are routinely carried out to observe the tympanic membrane and auditory canal. This is often done to detect signs of inflammation. The cochlea is a tonotopic structure. Hair cell responsiveness is position and frequency dependent, with hair cells located close to the cochlea apex transducing low frequencies and those at the base transducing high frequencies. The cochleogram aims to quantify hair cells all along the cochlea and consequently determine hair cell loss related to specific frequencies. This measure is then correlated with the ABR &amp; DPOAE results. Ototoxicity assessments evaluate the impact of drug candidates on the auditory and vestibular systems, de-risk hearing loss and balance disorders, define a safe dose, and optimize therapeutic benefits. These types of studies can be initiated during early development of a therapeutic solution, with ABR and otoscopic evaluations. Depending on the mechanism of action of the compound, studies can include DPOAE and cochleogram. Later in the development, a GLP (Good Laboratory Practice) ototoxicity study may be required based on otic related route of administration, target, or known potential otic toxicity

Adaptation et réorganisation psychique dans une maladie somatique chronique (rôle de la personnalité, des représentations de la maladie et de l'alexithymie)

A partir d'une étude comparative entre quatre pathologies somatiques différentes par l'organe atteint et le type de traitement, nous avons cherché à évaluer le rôle de la personnalité, des représentations de la maladie, de l'alexithymie et de la "réalité" de la maladie et du traitement, dans l'adaptation et la réorganisation psychique de sujets confrontés à une maladie à potentialité létale avec des traitements contraignants. Un autre objectif de ce travail est épistémologique dans les sciences psychologiques soulignant l'intérêt d'une double approche méthodologique, l'une expérimentale quantitative avec des autoquestionnaires validés, l'autre qualitative à partir d'études de cas analysés grâce au modèle psychanalytique. L'étude quantitative a mis en évidence qu'à sévérité "égale" et/ou type de traitement identique, les difficultés d'adaptation sont d'autant plus importantes que la dimension névrosisme est élevée, que les traits alexithymiques sont présents, la maladie représentant alors un poids plus important dans la vie. Au contraire, plus les dimensions extraversion, ouverture à l'expérience et conscience sont élevées, meilleure est l'adaptation et la représentation de la maladie. L'analyse qualitative psychanalytique de seize cas cliniques a montré que la réorganisation psychique d'un sujet confronté à une maladie somatique grave, chronique ou non est un processus subjectif dynamique qui nécessite un ajustement continuel du Moi pour rétablir et maintenir, dans la durée, un équilibre intrapsychique. Ce travail du Moi est modulé par l'importance des mécanismes de dégagement et la qualité des relations intersubjectives et dépend de l'équilibre entre investissements narcissiques et objectaux.From a comparative study between four somatic chronic diseases, différent by the affected organ and the type of treatment, we tried to evaluate the role of personality, illness perceptions and alexithymia and, reality of disease and treatment, in adjustment and psychic reorganisation of patients confronted to a potentiel lethal chronic disease and requiring restricting treatments. Another aim of this study is epistemological in psychological sciences, that is, to show the interest of a double methodological approach, one experimental with standardised self-questionnaires and the other one, qualitative with the psychoanalytical model to analyse clinical cases. The quantitative study showed that the adjustment to a chronic somatic illness depends on age, sexe. At equal severity and taking into account the type of treatment, adjustment difficulties are as much important as the dimension "neuroticism" and alexithymic characteristics are high and the burden of illness more important on life. The more, dimensions, extraversion, conscientiousness and openness, are high, the better adjustment and illness perception. The psychoanalytical analysis of sixteen clinical cases showed that the psychic reorganisation, in a serious chronic somatic illness, is a subjective and dynamic process which needs a continuous adjustment of Ego to restore and to maintain the psychic stability in a lasting tune. This Ego work is modulated by the importance of working-off mechanisms and the quality of intersubjective relationship, and the balance between narcissistic and objectal investments.NANTERRE-BU PARIS10 (920502102) / SudocSudocFranceF

Detecting Central Auditory Processing Disorders in Awake Mice

Mice are increasingly used as models of human-acquired neurological or neurodevelopmental conditions, such as autism, schizophrenia, and Alzheimer’s disease. All these conditions involve central auditory processing disorders, which have been little investigated despite their potential for providing interesting insights into the mechanisms behind such disorders. Alterations of the auditory steady-state response to 40 Hz click trains are associated with an imbalance between neuronal excitation and inhibition, a mechanism thought to be common to many neurological disorders. Here, we demonstrate the value of presenting click trains at various rates to mice with chronically implanted pins above the inferior colliculus and the auditory cortex for obtaining easy, reliable, and long-lasting access to subcortical and cortical complex auditory processing in awake mice. Using this protocol on a mutant mouse model of autism with a defect of the Shank3 gene, we show that the neural response is impaired at high click rates (above 60 Hz) and that this impairment is visible subcortically—two results that cannot be obtained with classical protocols for cortical EEG recordings in response to stimulation at 40 Hz. These results demonstrate the value and necessity of a more complete investigation of central auditory processing disorders in mouse models of neurological or neurodevelopmental disorders

Impulse Noise Induced Hidden Hearing Loss, Hair Cell Ciliary Changes and Oxidative Stress in Mice

International audienceRecent studies demonstrated that reversible continuous noise exposure may induce a temporary threshold shift (TTS) with a permanent degeneration of auditory nerve fibers, although hair cells remain intact. To probe the impact of TTS-inducing impulse noise exposure on hearing, CBA/J Mice were exposed to noise impulses with peak pressures of 145 dB SPL. We found that 30 min after exposure, the noise caused a mean elevation of ABR thresholds of ~30 dB and a reduction in DPOAE amplitude. Four weeks later, ABR thresholds and DPOAE amplitude were back to normal in the higher frequency region (8–32 kHz). At lower frequencies, a small degree of PTS remained. Morphological evaluations revealed a disturbance of the stereociliary bundle of outer hair cells, mainly located in the apical regions. On the other hand, the reduced suprathreshold ABR amplitudes remained until 4 weeks later. A loss of synapse numbers was observed 24 h after exposure, with full recovery two weeks later. Transmission electron microscopy revealed morphological changes at the ribbon synapses by two weeks post exposure. In addition, increased levels of oxidative stress were observed immediately after exposure, and maintained for a further 2 weeks. These results clarify the pathology underlying impulse noise-induced sensory dysfunction, and suggest possible links between impulse-noise injury, cochlear cell morphology, metabolic changes, and hidden hearing loss