Does the Diagnostic Accuracy and Rates of Face-to-Face Visits Occurring Shortly after an Asynchronized Teledermatology Consultation Justify Its Implementation? An 18-Month Cohort Study.

INTRODUCTION: In 2019, Maccabi Health Services (MHS) rolled out the store-and-forward "Dermadetect" teledermatology consultation (TC) application. Study goal was to analyze MHS records of TCs (August 2019-February 2021) for the rate and reasons for face-to-face consultations (FTFC) occurring shortly after a TC with emphasis on FTFCs resulting in a different diagnosis for the same indication. METHODS: The records of FTFCs held up shortly after TCs were reviewed and classified into cases marked as unsuited for teledermatology, cases in which the indication differed, and cases with the same indication, which were analyzed for concordance of diagnoses. RESULTS: Dermadetect was used by 12,815 MHS beneficiaries. In 30% of cases, following FTFC occurred within the subsequent 5 months, and 901 of them occurred in the subsequent 2 weeks and were analyzed. Thirty percent were not suited for teledermatology, 15% were held for a different indication, and 55% occurred for the same indication. The diagnosis concordance between the TC and recurrent FTFC for the same indication was 97.4%, with full concordance at 68.1% and partial concordance at 29.3%. Overall, 13 patients (1.4%) of the 901 patients using the application only once had a subsequent FTFC within 2 weeks and received a different diagnosis than the one given in the TC. CONCLUSIONS: When considering the implementation of store-and-forward TC's, a 30% rate of following FTFC's during the next 5 months should be considered when planning the reimbursement model. Diagnosis discordance may be disregarded due to its low rates.

Epigenetic and Neuronal Activity Markers Suggest the Recruitment of the Prefrontal Cortex and Hippocampus in the Three-Hit Model of Depression in Male PACAP Heterozygous Mice.

Depression and its increasing prevalence challenge patients, the healthcare system, and the economy. We recently created a mouse model based on the three-hit concept of depression. As genetic predisposition (first hit), we applied pituitary adenylate cyclase-activating polypeptide heterozygous mice on CD1 background. Maternal deprivation modeled the epigenetic factor (second hit), and the chronic variable mild stress was the environmental factor (third hit). Fluoxetine treatment was applied to test the predictive validity of our model. We aimed to examine the dynamics of the epigenetic marker acetyl-lysine 9 H3 histone (H3K9ac) and the neuronal activity marker FOSB in the prefrontal cortex (PFC) and hippocampus. Fluoxetine decreased H3K9ac in PFC in non-deprived animals, but a history of maternal deprivation abolished the effect of stress and SSRI treatment on H3K9ac immunoreactivity. In the hippocampus, stress decreased, while SSRI increased H3K9ac immunosignal, unlike in the deprived mice, where the opposite effect was detected. FOSB in stress was stimulated by fluoxetine in the PFC, while it was inhibited in the hippocampus. The FOSB immunoreactivity was almost completely abolished in the hippocampus of the deprived mice. This study showed that FOSB and H3K9ac were modulated in a territory-specific manner by early life adversities and later life stress interacting with the effect of fluoxetine therapy supporting the reliability of our model.

Fluoxetine treatment supports predictive validity of the three hit model of depression in male PACAP heterozygous mice and underpins the impact of early life adversity on therapeutic efficacy.

According to the three hit concept of depression, interaction of genetic predisposition altered epigenetic programming and environmental stress factors contribute to the disease. Earlier we demonstrated the construct and face validity of our three hit concept-based mouse model. In the present work, we aimed to examine the predictive validity of our model, the third willnerian criterion. Fluoxetine treatment was applied in chronic variable mild stress (CVMS)-exposed (environmental hit) CD1 mice carrying one mutated allele of pituitary adenylate cyclase-activating polypeptide gene (genetic hit) that were previously exposed to maternal deprivation (epigenetic hit) vs. controls. Fluoxetine reduced the anxiety level in CVMS-exposed mice in marble burying test, and decreased the depression level in tail suspension test if mice were not deprived maternally. History of maternal deprivation caused fundamental functional-morphological changes in response to CVMS and fluoxetine treatment in the corticotropin-releasing hormone-producing cells of the bed nucleus of the stria terminalis and central amygdala, in tyrosine-hydroxylase content of ventral tegmental area, in urocortin 1-expressing cells of the centrally projecting Edinger-Westphal nucleus, and serotonergic cells of the dorsal raphe nucleus. The epigenetic background of alterations was approved by altered acetylation of histone H3. Our findings further support the validity of both the three hit concept and that of our animal model. Reversal of behavioral and functional-morphological anomalies by fluoxetine treatment supports the predictive validity of the model. This study highlights that early life stress does not only interact with the genetic and environmental factors, but has strong influence also on therapeutic efficacy.