RESUMEN
OBJECTIVE: We aimed to describe characteristics of patients with ATTR variant polyneuropathy (ATTRv-PN) and ATTRv-mixed and assess the real-world use and safety profile of tafamidis meglumine 20mg. METHODS: Thirty-eight French hospitals were invited. Patient files were reviewed to identify clinical manifestations, diagnostic methods, and treatment compliance. RESULTS: Four hundred and thirteen patients (296 ATTRv-PN, 117 ATTRv-mixed) were analyzed. Patients were predominantly male (68.0%) with a mean age of 57.2±17.2 years. Interval between first symptom(s) and diagnosis was 3.4±4.3 years. First symptoms included sensory complaints (85.9%), dysautonomia (38.5%), motor deficits (26.4%), carpal tunnel syndrome (31.5%), shortness of breath (13.3%), and unexplained weight loss (16.0%). Mini-invasive accessory salivary gland or punch skin and nerve biopsies were most common, with a performance of 78.8-100%. TTR genetic sequencing, performed in all patients, revealed 31 TTR variants. Tafamidis meglumine was initiated in 156/214 (72.9%) ATTRv-PN patients at an early disease stage. Median treatment duration was 6.00 years in ATTRv-PN and 3.42 years in ATTRv-mixed patients. Tafamidis was well tolerated, with 20 adverse events likely related to study drug among the 336 patients. CONCLUSION: In France, ATTRv patients are usually identified early thanks to the national network and the help of diagnosis combining genetic testing and mini-invasive biopsies.
RESUMEN
Individual vulnerability to the reinforcing effects of drugs appear to be a crucial factor in the development of addiction in humans. In the rat, individuals at risk for psychostimulant self-administration (SA) may be identified from their locomotor reactivity to a stress situation such as exposure to a novel environment. Animals with higher locomotor responses to novelty (High Responders, HR) tend to acquire amphetamine SA, while animals with the lower responses (Low Responders, LR) do not. In this study, we examined whether activity of dopaminergic (DA) and serotoninergic (5-HT) systems differed between HR and LR animals. These transmitter systems are thought to be involved in the reinforcing effects of psychostimulants. Animals from both groups were sacrificed under basal conditions and after exposure for 30 or 120 min to a novel environment, and the DA, 3,4-dihydroxyphenylacetic acid (DOPAC), 5-HT, and 5-hydroxyindolacetic acid (5-HIAA) contents were determined in the prefrontal cortex, nucleus accumbens and striatum. The HR rats displayed a specific neurochemical pattern: a higher DOPAC/DA ratio in the nucleus accumbens and striatum and a lower one in the prefrontal cortex. Furthermore, HR animals had lower overall 5-HT and 5-HIAA levels, corresponding to the mean of these compounds for the three structures studied over the three environmental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
