Aging is accompanied by changes in the quantity and quality of sleep. Obstructive sleep apnea (OS... more Aging is accompanied by changes in the quantity and quality of sleep. Obstructive sleep apnea (OSA) is also more prevalent in the older population. Although severe OSA has been linked to a higher risk of cardiovascular disease regardless of adult age, clinical consequences of mild-to-moderate OSA in the older adults are still uncertain. Objectives: To investigate the relationships between severity and metabolic, cognitive, and functional characteristics in community-dwelling older adults from a representative sample of the city of São Paulo. Methods: In total, 199 participants of the first follow-up of the São Paulo Epidemiologic Sleep Study (EPISONO, São Paulo, Brazil) >60 years were cross-sectionally assessed through questionnaires, physical evaluations, laboratory tests, and full inlab polysomnography (PSG). Three groups according to the OSA severity were compared according to sociodemographic characteristics, anthropometric measures, PSG parameters, the frequency of comorbidities, and the use of medications. Results: Participants' age ranged from 60 to 87 years with a mean of 70.02 ± 7.31, 59.8% female. In the univariate analysis, body mass index (BMI, kg/m 2) (p = 0.049) and waist circumference (p = 0.005) were significantly higher in the participants with moderate OSA, but not among those with severe OSA. Participants with severe OSA had a higher arousal index (p = 0.007). Multivariate analysis showed that severe OSA was significantly associated with hypertension (p = 0.005), heart diseases (p = 0.025), and the use of two or more medications (p = 0.035). Conclusion: In a population-based study, severe, but not mild-to-moderate, OSA in older adults was associated with hypertension and the use of more medications. As age advances, anthropometric indicators of obesity may not increase the risk of severe OSA.
OBJECTIVE/BACKGROUND The real-world experience of people with narcolepsy is not well understood. ... more OBJECTIVE/BACKGROUND The real-world experience of people with narcolepsy is not well understood. PATIENTS/METHODS The Nexus Narcolepsy Registry (NCT02769780) is a longitudinal, web-based patient registry of self-reported data from adults with physician-diagnosed narcolepsy. Surveys were electronically distributed every 6 months; the current analysis reports registry population demographics, narcolepsy diagnosis journey, and predictors of diagnostic delays. RESULTS The registry population included in this analysis (N = 1024) was predominantly female (85%) and White (92%), with a mean age of 37.7 years. Most participants had education/training beyond high school (93%). Mean (median) reported ages at narcolepsy symptom onset, first consultation for symptoms, and narcolepsy diagnosis were 18.1 (16), 26.4 (24), and 30.1 (28) years, respectively. A majority (59%) of participants reported ≥1 misdiagnosis, and 29% reported consulting ≥5 physicians before narcolepsy diagnosis. More than half (56%) of participants' first consultations for narcolepsy symptoms were with a general practitioner, whereas the diagnosing clinician was usually a sleep specialist (64%) or neurologist (27%). Pediatric symptom onset was associated with a longer mean interval to first consultation than adult symptom onset (10.7 and 4.6 years, respectively; P < 0.001) and a longer mean interval between first consultation and diagnosis (4.5 and 2.2 years, respectively; P < 0.001). Overall, mean (95% CI) time from symptom onset to diagnosis was 11.8 (11.1-12.5) years. CONCLUSIONS The Nexus Narcolepsy Registry data indicate that onset of narcolepsy symptoms frequently occurs in childhood or adolescence. In many individuals, the diagnostic process is long and involves multiple physicians and frequent misdiagnosis.
Introduction: Narcolepsy is a lifelong neurological disorder with disease-onset largely occurring... more Introduction: Narcolepsy is a lifelong neurological disorder with disease-onset largely occurring during childhood/adolescence. Few treatments have been formally evaluated in pediatric populations. Sodium oxybate (Xyrem®) is approved in the United States (US) for the treatment of cataplexy and excessive daytime sleepiness in patients with narcolepsy. The FDA requested a study of sodium oxybate (SXB) in pediatric narcolepsy patients. Methods: Children and adolescents (7-16 years) diagnosed with narcolepsy with cataplexy who were on SXB treatment or were SXB-naïve were eligible. SXB-naïve patients were titrated to a stable dose. After a stable dose period (SD), patients entered a two-week double-blind, placebo-controlled withdrawal period (DB) and were randomized 1:1 to receive either SXB (at stable dose) or placebo. Efficacy assessments compared measurements during or at the end of the DB period, relative to the SD period. Results: The trial enrolled 106 patients; 63 were randomized. Among randomized patients, 41% were aged 7-11, 44% were female, and 38% were on SXB treatment at study entry. A pre-planned interim analysis of 35 patients showed that efficacy was achieved (p<0.005) on the primary endpoint (reduction in weekly cataplexy attacks). The double-blind randomized withdrawal period was therefore terminated early on the advice of the Data Safety Monitoring Board, and in agreement with the FDA. Preliminarily reported adverse events were similar to those seen in adults and in prior pediatric experiences. Results from the randomized cohort will be presented for primary endpoint, key secondary endpoints (Clinical Global Impression of Change (CGIc) for cataplexy severity and change in the Epworth Sleepiness Scale for Children and Adolescents (ESS [CHAD]) score), and safety findings during the DB period. Conclusion: Preliminary results indicate that sodium oxybate is efficacious in reducing cataplexy in pediatric patients with narcolepsy. The safety profile appears similar to that previously observed in adult and pediatric populations. Support (If Any): Jazz Pharmaceuticals.
Objective: To describe the frequency of misdiagnoses and comorbidities in participants diagnosed ... more Objective: To describe the frequency of misdiagnoses and comorbidities in participants diagnosed with narcolepsy. Background: Narcolepsy diagnosis can be challenging. Presence of comorbidities and overlapping symptoms between narcolepsy and other conditions may contribute to diagnostic delay and misdiagnosis. Symptoms of narcolepsy may be mistaken for conditions such as depression or psychiatric illness. Design/Methods: The Nexus Narcolepsy Registry is an ongoing, longitudinal, patient-reported, web-based database of adult participants diagnosed with narcolepsy. Data was collected from June 2015–September 2017, with 1024 participants completing ≥1 assessment. Participants were categorized based on self-reported pediatric ( Results: Nearly 60% (59.3%; 95% confidence interval [CI]: 56.2%–62.5%) of participants reported receiving ≥1 misdiagnosis to explain their narcolepsy symptoms before receiving a narcolepsy diagnosis. The most common misdiagnoses, regardless of age of onset, included: depression (31.3%), anxiety disorder (16.3%), attention deficit/hyperactivity disorder (ADHD, 16.2%), insomnia (14.4%), and hypersomnia (14.3%). Of the most common misdiagnoses, ADHD was more frequent in those with pediatric onset compared to those with adult onset (19.2% vs. 12.3%, p=0.005), as was bipolar disorder (14.2% vs. 9.1%, p=0.019). Epilepsy was also more frequent in pediatric versus adult onset of narcolepsy symptoms (7.8% vs. 3.7%, p=0.013), as was schizophrenia (5.4% vs. 2.1%, p=0.015). The most frequently reported comorbidities, regardless of age of onset, were: depression (34.0%), anxiety disorder (27.1%), obstructive sleep apnea (OSA, 11.6%), hypersomnia (9.9%), and ADHD (9.6%). Of the most common comorbidities, OSA occurred more frequently among those with adult symptom onset (14.2%) versus pediatric symptom onset (9.6%; p=0.033). Conclusions: Patients with narcolepsy may be misdiagnosed and/or have various comorbidities, including psychiatric conditions. These findings are consistent with what has previously been reported in the literature. Disclosure: Dr. Ohayon has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Jazz Pharmaceuticals. Dr. Ohayon has received research support from Jazz Pharmaceuticals. Dr. Thorpy has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Balance Therapeutics, Harmony Biosciences, LLC, Jazz Pharmaceuticals, Merck & Co. Dr. Thorpy has received research support from Balance Therapeutics, Harmony Biosciences, LLC, and Jazz Pharmaceuticals. Dr. Black has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Jazz Pharmaceuticals. Dr. Williams has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with ICON Clinical Research. Dr. Williams has received research support from ICON Clinical Research received funding from Jazz Pharmaceuticals to conduct this research. Dr. Pasta has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with ICON Clinical Research. Dr. Pasta has received research support from ICON Clinical Research and Jazz Pharmaceuticals. Dr. Hyman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Jazz Pharmaceuticals. Dr. Villa has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Jazz Pharmaceuticals.
Objective: To explore factors associated with the use or discontinuation of different treatments ... more Objective: To explore factors associated with the use or discontinuation of different treatments or combinations for the management of narcolepsy. Background: No published studies identify factors associated with use of different medications for management of narcolepsy and few studies report on associated discontinuation rates. Design/Methods: Analyses were conducted using data from the Nexus Narcolepsy Registry, an ongoing study of adults diagnosed with narcolepsy. Using the first two 6-month assessments, 4 logistic regression models were run to identify variables significantly ( P Results: Of the 970 assessments analyzed, 91.7% reported currently taking ≥1 narcolepsy medication. The majority (57.9%) of assessments reported use of stimulants, 45.5% antidepressants, 39.8% M/A, and 30.3% SXB. Stimulant use was associated with: M/A non-use ( P P P =0.001), and currently working for pay ( P =0.021). Antidepressant use was associated with: M/A use ( P P P≤ 0.001), cataplexy history ( P =0.006), higher education ( P =0.015), and residing in Southern or Midwestern US (vs. Western US, P ≤0.036). Covariates significantly associated with SXB treatment were living in any US region (versus ex-US, P≤ 0.001), higher education ( P =0.008), and male gender ( P =0.047). M/A treatment was associated with stimulant non-use ( P P =0.008), and current employment ( P =0.004). There were statistically significant differences in discontinuation rates ( P Conclusions: Most participants took ≥1 narcolepsy medications. Factors associated with medication use were other concomitant medications, sex, region, and work status. SXB was associated with the lowest discontinuation rate in the previous 6-month period. Study Supported by: Jazz Pharmaceuticals. Disclosure: Dr. Villa, MS has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with is an employees of Jazz Pharmaceuticals, Inc., who, in the course of this employment, has received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals plc. Dr. Pasta, MS has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with is an employee of ICON Clinical Research, which was paid by Jazz Pharmaceuticals to provide statistical advice services on this project. Dr. Black has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr Black is a part-time employee of Jazz Pharmaceuticals and shareholder of Jazz Pharmaceuticals plc. Dr. Bujanover, MD has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with is an employee of Jazz Pharmaceuticals, Inc., who, in the course of this employment, have received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals plc. Dr. Cisternas has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with is an employee of ICON Clinical Research, which was paid by Jazz Pharmaceuticals to provide statistical services on this project. Dr. Ohayon has nothing to disclose. Dr. Thorpy has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with has received consultancy fees from Jazz Pharmaceuticals, Merck & Co, Inc., and Teva Pharmaceutical Industries Ltd; and has been a member of the speakers’ bureau for Jazz Pharmaceuticals and Cephalon, Inc. (now Teva Pharmaceutical Industries, Ltd.). Dr. Thorpy has received research support from has received research/grant support and consultancy fees from Jazz Pharmaceuticals, Merck & Co, Inc., and Teva Pharmaceutical Industries Ltd.
Objective: Understanding the predisposing sleep and medical conditions associated with Chronic GE... more Objective: Understanding the predisposing sleep and medical conditions associated with Chronic GERD and their evolution in the general population. Background: GERD is a chronic digestive system disease caused by the spilling of stomach content back into the esophagus. The prevalence of GERD and its evolution with other comorbidities has not been previously assessed in population-based studies in the US. Studying the evolution of GERD in conjunction with sleep, medical and psychiatric conditions can provide important information about the chronicity of the disease and predisposing conditions. Design/Methods: A representative sample of the US general adult population (12,218 subjects at wave 1 (W1) and 10,830 subjects at wave 2 (W2)) was interviewed twice with the Sleep EVAL system. Three years elapsed between the two waves. The participation rate was 88%. Results: According to this study, the prevalence of GERD in the US general population is between 10.6 and 12.4%. Prevalence of GERD increased with age. The greatest risk of developing chronic GERD was found among subjects aged between 45 and 64 years. Among the sleep disorders, nocturnal awakenings were significantly more common both in wave 1 and wave 2. Major depressive disorder was also more likely only in chronic cases of GERD. Obstructive sleep apnea, medical conditions such as diseases of the musculoskeletal system and connective tissue, hypercholesterolemia, and hypertension were also good predictors of GERD chronicity. Finally, high BMI was significantly associated with both chronic GERD and sleep apnea. Smoking and/or drinking alcohol and coffee did not predict chronicity. Conclusions: Nocturnal awakenings are highly prevalent among individuals affected by GERD. GERD chronicity is strongly predicted by insomnia disorder, sleep dissatisfaction, difficulty initiating sleep, major depressive disorder and various medical disorders. Physicians must be aware of these predisposing conditions and factors of chronicity involving Sleep Disorders. Study Supported by: Educational grant from Takeda Pharmaceuticals. Disclosure: Dr. Ohayon has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals, Inc. as a speaker. Dr. Ohayon has received research support from Jazz Pharmaceuticals and Takeda Pharmaceuticals. Dr. Milesi has received personal compensation for activities with Sanofi Genzyme as a speaker. Dr. van Dijk has received personal compensation for activities with Takeda Pharmaceuticals as an employee.
Objective: We explore the association between the intensity in outdoor nighttime light intensity ... more Objective: We explore the association between the intensity in outdoor nighttime light intensity and the sleep habits of the American population. Background: Artificial light at night extends outdoor activities beyond dusk and increases security and safety of the population. In cities, the use of outdoor lights has reduced the exposure to darkness in the 24 hour period. Methods: A representative sample of 15,863 individuals was interviewed by telephone using the Sleep-EVAL expert system between the years 2002 and 2009 and geolocated by latitude and longitude. Data collected during the interviews included sleep habits, sleep, medical and psychiatric disorders. Outdoor nighttime light radiance (NLR) for the locations of the interviews was obtained for the years corresponding to the interviews from the Defense Meteorological Satellite Program’s Operational Linescan System (DMSP/OLS) nighttime imagery. Results: NLR to be associated with a shift in the sleep habits of the general population, resulting in delayed bedtime (p<0.0001) and wake up time (p<0.0001). Overall, NLR is associated with a shortening of the sleep duration (p<0.01) and increased daytime sleepiness (p<0.0001). Exposure to greater NLR also increases the dissatisfaction with sleep quantity and quality (p<0.0001) and the likelihood of having a circadian rhythm disorder (p<0.0001). Conclusions: Outdoor nighttime light exposure is strongly associated with changes in sleep habits and impact our daytime functioning increasing the risks of excessive sleepiness. Disclosure: Dr. Ohayon has received personal compensation for activities with Jazz Pharmaceuticals and Pfizer Inc. Dr. Milesi has nothing to disclose.
L'echelle relationnelle apparait au terme de cette etude comparable a la MADRS (Depression Ra... more L'echelle relationnelle apparait au terme de cette etude comparable a la MADRS (Depression Rating Scale) en ce qui concerne la mesure de la gravite du syndrome depressif. Elle presente l'avantage d'une homogeneite plus grande et d'un pouvoir separateur meilleur en ce qui concerne les categories de patients etudies
Premiere experience de realisation d'un programme informatique capable de reproduire la demar... more Premiere experience de realisation d'un programme informatique capable de reproduire la demarche diagnostique telle qu'elle est presentee dans l'arbre de decision du DSMIII: le modele de raisonnement utilise a ete nomme ADINFER
BACKGROUND The aim of this study was to evaluate the impact of different therapy regimens, includ... more BACKGROUND The aim of this study was to evaluate the impact of different therapy regimens, including sodium oxybate (SXB)-containing regimens, on patient-reported outcomes (PROs) in people with narcolepsy. METHODS Online surveys were used to collect information from persons with narcolepsy in the Nexus Narcolepsy Registry. Surveys contained questionnaires assessing self-reported sleep quality (SQ; via single question), daytime sleepiness and function (Epworth Sleepiness Scale and Functional Outcomes of Sleep Questionnaire), health-related quality of life (HRQoL; 36-Item Short Form Health Survey [SF-36]), work productivity and impairment (Work Productivity and Activity Impairment: Specific Health Problem), and history of injuries or motor vehicle accidents. Treatment with SXB (including monotherapy or combination therapy; SXB group) was compared with non-SXB therapy (No SXB group). The P values presented are nominal, as there are no adjustments for multiplicity. RESULTS From June 2015 through December 2017, 983 participants completed 1760 surveys. SQ and daytime functioning scores were better in the SXB group compared with the No SXB group (all P < 0.001). HRQoL scores were better for the SXB group compared with the No SXB group for the SF-36 Physical Component (P = 0.016), Mental Component (P < 0.001), and all 8 subscales. Additionally, PROs were better for the SXB group for presenteeism, overall work and activity impairment, and risk of motor vehicle accidents (all P ≤ 0.001). CONCLUSION Based on participants' self-assessments, treatment regimens with SXB were associated with better outcomes than regimens not containing SXB across many PROs, including SQ, HRQoL, work and activities, and risk of traffic accidents. CLINICALTRIALS. GOV IDENTIFIER NCT02769780.
Introduction: Nonrestorative sleep (NRS) is one of the sleep disturbances that is under-appreciat... more Introduction: Nonrestorative sleep (NRS) is one of the sleep disturbances that is under-appreciated. Some studies have set its prevalence at around 10% of the general population but definitions are heterogenous. Despite its frequency, studies that paid attention to that symptom are disparate and have often taken many routes. Our aim is to examine its prevalence, its incidence and its predictive factors. Methods: The initial study was carried with 15,929 individuals from 15 US States. The longitudinal study was carried on in eight of these states. A total of 12,218 subjects were interviewed by phone during the first wave (W1) and 10,930 at the second wave (W2) three years apart. The analyses were carried on the subjects who participated in both interviews (N=10,930). NRS was assessed using a series of five questions. The global score determined the presence/absence of NRS. Results: A total of 14.7% (CI95%: 14%-15.4%) reported NRS at W1. At follow-up, 13.1% (CI95%: 12.5%-13.7%) reported NRS. The incidence per year was 2.3%. NRS was chronic in 28.9% of cases. NRS occurred alone (i.e. without any other insomnia symptoms) in 5% of the sample at W1 and 3.6% at W2. 22.2% of those with NRS alone at W1 reported other insomnia symptoms at W2. Sleep duration was at least 6h30 in 81.6% of NRS alone cases at W1 and 76.5% at W2. Daytime repercussions were reported by 66.2% of NRS alone at W1 and 52.8% at W2. NRS alone (RR: 2.4) or in combination with insomnia symptoms (RR: 3.4) was one of the strongest predictors for developing a Major Depressive Disorder at W2. Conclusion: NRS is a sleep disturbance that has some unique features that distinguish it from insomnia symptoms. Nonetheless, it can have a profound impact on daily life and can lead to further difficulties in other areas if not addressed properly.
Aging is accompanied by changes in the quantity and quality of sleep. Obstructive sleep apnea (OS... more Aging is accompanied by changes in the quantity and quality of sleep. Obstructive sleep apnea (OSA) is also more prevalent in the older population. Although severe OSA has been linked to a higher risk of cardiovascular disease regardless of adult age, clinical consequences of mild-to-moderate OSA in the older adults are still uncertain. Objectives: To investigate the relationships between severity and metabolic, cognitive, and functional characteristics in community-dwelling older adults from a representative sample of the city of São Paulo. Methods: In total, 199 participants of the first follow-up of the São Paulo Epidemiologic Sleep Study (EPISONO, São Paulo, Brazil) >60 years were cross-sectionally assessed through questionnaires, physical evaluations, laboratory tests, and full inlab polysomnography (PSG). Three groups according to the OSA severity were compared according to sociodemographic characteristics, anthropometric measures, PSG parameters, the frequency of comorbidities, and the use of medications. Results: Participants' age ranged from 60 to 87 years with a mean of 70.02 ± 7.31, 59.8% female. In the univariate analysis, body mass index (BMI, kg/m 2) (p = 0.049) and waist circumference (p = 0.005) were significantly higher in the participants with moderate OSA, but not among those with severe OSA. Participants with severe OSA had a higher arousal index (p = 0.007). Multivariate analysis showed that severe OSA was significantly associated with hypertension (p = 0.005), heart diseases (p = 0.025), and the use of two or more medications (p = 0.035). Conclusion: In a population-based study, severe, but not mild-to-moderate, OSA in older adults was associated with hypertension and the use of more medications. As age advances, anthropometric indicators of obesity may not increase the risk of severe OSA.
OBJECTIVE/BACKGROUND The real-world experience of people with narcolepsy is not well understood. ... more OBJECTIVE/BACKGROUND The real-world experience of people with narcolepsy is not well understood. PATIENTS/METHODS The Nexus Narcolepsy Registry (NCT02769780) is a longitudinal, web-based patient registry of self-reported data from adults with physician-diagnosed narcolepsy. Surveys were electronically distributed every 6 months; the current analysis reports registry population demographics, narcolepsy diagnosis journey, and predictors of diagnostic delays. RESULTS The registry population included in this analysis (N = 1024) was predominantly female (85%) and White (92%), with a mean age of 37.7 years. Most participants had education/training beyond high school (93%). Mean (median) reported ages at narcolepsy symptom onset, first consultation for symptoms, and narcolepsy diagnosis were 18.1 (16), 26.4 (24), and 30.1 (28) years, respectively. A majority (59%) of participants reported ≥1 misdiagnosis, and 29% reported consulting ≥5 physicians before narcolepsy diagnosis. More than half (56%) of participants' first consultations for narcolepsy symptoms were with a general practitioner, whereas the diagnosing clinician was usually a sleep specialist (64%) or neurologist (27%). Pediatric symptom onset was associated with a longer mean interval to first consultation than adult symptom onset (10.7 and 4.6 years, respectively; P < 0.001) and a longer mean interval between first consultation and diagnosis (4.5 and 2.2 years, respectively; P < 0.001). Overall, mean (95% CI) time from symptom onset to diagnosis was 11.8 (11.1-12.5) years. CONCLUSIONS The Nexus Narcolepsy Registry data indicate that onset of narcolepsy symptoms frequently occurs in childhood or adolescence. In many individuals, the diagnostic process is long and involves multiple physicians and frequent misdiagnosis.
Introduction: Narcolepsy is a lifelong neurological disorder with disease-onset largely occurring... more Introduction: Narcolepsy is a lifelong neurological disorder with disease-onset largely occurring during childhood/adolescence. Few treatments have been formally evaluated in pediatric populations. Sodium oxybate (Xyrem®) is approved in the United States (US) for the treatment of cataplexy and excessive daytime sleepiness in patients with narcolepsy. The FDA requested a study of sodium oxybate (SXB) in pediatric narcolepsy patients. Methods: Children and adolescents (7-16 years) diagnosed with narcolepsy with cataplexy who were on SXB treatment or were SXB-naïve were eligible. SXB-naïve patients were titrated to a stable dose. After a stable dose period (SD), patients entered a two-week double-blind, placebo-controlled withdrawal period (DB) and were randomized 1:1 to receive either SXB (at stable dose) or placebo. Efficacy assessments compared measurements during or at the end of the DB period, relative to the SD period. Results: The trial enrolled 106 patients; 63 were randomized. Among randomized patients, 41% were aged 7-11, 44% were female, and 38% were on SXB treatment at study entry. A pre-planned interim analysis of 35 patients showed that efficacy was achieved (p<0.005) on the primary endpoint (reduction in weekly cataplexy attacks). The double-blind randomized withdrawal period was therefore terminated early on the advice of the Data Safety Monitoring Board, and in agreement with the FDA. Preliminarily reported adverse events were similar to those seen in adults and in prior pediatric experiences. Results from the randomized cohort will be presented for primary endpoint, key secondary endpoints (Clinical Global Impression of Change (CGIc) for cataplexy severity and change in the Epworth Sleepiness Scale for Children and Adolescents (ESS [CHAD]) score), and safety findings during the DB period. Conclusion: Preliminary results indicate that sodium oxybate is efficacious in reducing cataplexy in pediatric patients with narcolepsy. The safety profile appears similar to that previously observed in adult and pediatric populations. Support (If Any): Jazz Pharmaceuticals.
Objective: To describe the frequency of misdiagnoses and comorbidities in participants diagnosed ... more Objective: To describe the frequency of misdiagnoses and comorbidities in participants diagnosed with narcolepsy. Background: Narcolepsy diagnosis can be challenging. Presence of comorbidities and overlapping symptoms between narcolepsy and other conditions may contribute to diagnostic delay and misdiagnosis. Symptoms of narcolepsy may be mistaken for conditions such as depression or psychiatric illness. Design/Methods: The Nexus Narcolepsy Registry is an ongoing, longitudinal, patient-reported, web-based database of adult participants diagnosed with narcolepsy. Data was collected from June 2015–September 2017, with 1024 participants completing ≥1 assessment. Participants were categorized based on self-reported pediatric ( Results: Nearly 60% (59.3%; 95% confidence interval [CI]: 56.2%–62.5%) of participants reported receiving ≥1 misdiagnosis to explain their narcolepsy symptoms before receiving a narcolepsy diagnosis. The most common misdiagnoses, regardless of age of onset, included: depression (31.3%), anxiety disorder (16.3%), attention deficit/hyperactivity disorder (ADHD, 16.2%), insomnia (14.4%), and hypersomnia (14.3%). Of the most common misdiagnoses, ADHD was more frequent in those with pediatric onset compared to those with adult onset (19.2% vs. 12.3%, p=0.005), as was bipolar disorder (14.2% vs. 9.1%, p=0.019). Epilepsy was also more frequent in pediatric versus adult onset of narcolepsy symptoms (7.8% vs. 3.7%, p=0.013), as was schizophrenia (5.4% vs. 2.1%, p=0.015). The most frequently reported comorbidities, regardless of age of onset, were: depression (34.0%), anxiety disorder (27.1%), obstructive sleep apnea (OSA, 11.6%), hypersomnia (9.9%), and ADHD (9.6%). Of the most common comorbidities, OSA occurred more frequently among those with adult symptom onset (14.2%) versus pediatric symptom onset (9.6%; p=0.033). Conclusions: Patients with narcolepsy may be misdiagnosed and/or have various comorbidities, including psychiatric conditions. These findings are consistent with what has previously been reported in the literature. Disclosure: Dr. Ohayon has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Jazz Pharmaceuticals. Dr. Ohayon has received research support from Jazz Pharmaceuticals. Dr. Thorpy has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Balance Therapeutics, Harmony Biosciences, LLC, Jazz Pharmaceuticals, Merck & Co. Dr. Thorpy has received research support from Balance Therapeutics, Harmony Biosciences, LLC, and Jazz Pharmaceuticals. Dr. Black has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Jazz Pharmaceuticals. Dr. Williams has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with ICON Clinical Research. Dr. Williams has received research support from ICON Clinical Research received funding from Jazz Pharmaceuticals to conduct this research. Dr. Pasta has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with ICON Clinical Research. Dr. Pasta has received research support from ICON Clinical Research and Jazz Pharmaceuticals. Dr. Hyman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Jazz Pharmaceuticals. Dr. Villa has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Jazz Pharmaceuticals.
Objective: To explore factors associated with the use or discontinuation of different treatments ... more Objective: To explore factors associated with the use or discontinuation of different treatments or combinations for the management of narcolepsy. Background: No published studies identify factors associated with use of different medications for management of narcolepsy and few studies report on associated discontinuation rates. Design/Methods: Analyses were conducted using data from the Nexus Narcolepsy Registry, an ongoing study of adults diagnosed with narcolepsy. Using the first two 6-month assessments, 4 logistic regression models were run to identify variables significantly ( P Results: Of the 970 assessments analyzed, 91.7% reported currently taking ≥1 narcolepsy medication. The majority (57.9%) of assessments reported use of stimulants, 45.5% antidepressants, 39.8% M/A, and 30.3% SXB. Stimulant use was associated with: M/A non-use ( P P P =0.001), and currently working for pay ( P =0.021). Antidepressant use was associated with: M/A use ( P P P≤ 0.001), cataplexy history ( P =0.006), higher education ( P =0.015), and residing in Southern or Midwestern US (vs. Western US, P ≤0.036). Covariates significantly associated with SXB treatment were living in any US region (versus ex-US, P≤ 0.001), higher education ( P =0.008), and male gender ( P =0.047). M/A treatment was associated with stimulant non-use ( P P =0.008), and current employment ( P =0.004). There were statistically significant differences in discontinuation rates ( P Conclusions: Most participants took ≥1 narcolepsy medications. Factors associated with medication use were other concomitant medications, sex, region, and work status. SXB was associated with the lowest discontinuation rate in the previous 6-month period. Study Supported by: Jazz Pharmaceuticals. Disclosure: Dr. Villa, MS has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with is an employees of Jazz Pharmaceuticals, Inc., who, in the course of this employment, has received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals plc. Dr. Pasta, MS has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with is an employee of ICON Clinical Research, which was paid by Jazz Pharmaceuticals to provide statistical advice services on this project. Dr. Black has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr Black is a part-time employee of Jazz Pharmaceuticals and shareholder of Jazz Pharmaceuticals plc. Dr. Bujanover, MD has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with is an employee of Jazz Pharmaceuticals, Inc., who, in the course of this employment, have received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals plc. Dr. Cisternas has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with is an employee of ICON Clinical Research, which was paid by Jazz Pharmaceuticals to provide statistical services on this project. Dr. Ohayon has nothing to disclose. Dr. Thorpy has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with has received consultancy fees from Jazz Pharmaceuticals, Merck & Co, Inc., and Teva Pharmaceutical Industries Ltd; and has been a member of the speakers’ bureau for Jazz Pharmaceuticals and Cephalon, Inc. (now Teva Pharmaceutical Industries, Ltd.). Dr. Thorpy has received research support from has received research/grant support and consultancy fees from Jazz Pharmaceuticals, Merck & Co, Inc., and Teva Pharmaceutical Industries Ltd.
Objective: Understanding the predisposing sleep and medical conditions associated with Chronic GE... more Objective: Understanding the predisposing sleep and medical conditions associated with Chronic GERD and their evolution in the general population. Background: GERD is a chronic digestive system disease caused by the spilling of stomach content back into the esophagus. The prevalence of GERD and its evolution with other comorbidities has not been previously assessed in population-based studies in the US. Studying the evolution of GERD in conjunction with sleep, medical and psychiatric conditions can provide important information about the chronicity of the disease and predisposing conditions. Design/Methods: A representative sample of the US general adult population (12,218 subjects at wave 1 (W1) and 10,830 subjects at wave 2 (W2)) was interviewed twice with the Sleep EVAL system. Three years elapsed between the two waves. The participation rate was 88%. Results: According to this study, the prevalence of GERD in the US general population is between 10.6 and 12.4%. Prevalence of GERD increased with age. The greatest risk of developing chronic GERD was found among subjects aged between 45 and 64 years. Among the sleep disorders, nocturnal awakenings were significantly more common both in wave 1 and wave 2. Major depressive disorder was also more likely only in chronic cases of GERD. Obstructive sleep apnea, medical conditions such as diseases of the musculoskeletal system and connective tissue, hypercholesterolemia, and hypertension were also good predictors of GERD chronicity. Finally, high BMI was significantly associated with both chronic GERD and sleep apnea. Smoking and/or drinking alcohol and coffee did not predict chronicity. Conclusions: Nocturnal awakenings are highly prevalent among individuals affected by GERD. GERD chronicity is strongly predicted by insomnia disorder, sleep dissatisfaction, difficulty initiating sleep, major depressive disorder and various medical disorders. Physicians must be aware of these predisposing conditions and factors of chronicity involving Sleep Disorders. Study Supported by: Educational grant from Takeda Pharmaceuticals. Disclosure: Dr. Ohayon has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals, Inc. as a speaker. Dr. Ohayon has received research support from Jazz Pharmaceuticals and Takeda Pharmaceuticals. Dr. Milesi has received personal compensation for activities with Sanofi Genzyme as a speaker. Dr. van Dijk has received personal compensation for activities with Takeda Pharmaceuticals as an employee.
Objective: We explore the association between the intensity in outdoor nighttime light intensity ... more Objective: We explore the association between the intensity in outdoor nighttime light intensity and the sleep habits of the American population. Background: Artificial light at night extends outdoor activities beyond dusk and increases security and safety of the population. In cities, the use of outdoor lights has reduced the exposure to darkness in the 24 hour period. Methods: A representative sample of 15,863 individuals was interviewed by telephone using the Sleep-EVAL expert system between the years 2002 and 2009 and geolocated by latitude and longitude. Data collected during the interviews included sleep habits, sleep, medical and psychiatric disorders. Outdoor nighttime light radiance (NLR) for the locations of the interviews was obtained for the years corresponding to the interviews from the Defense Meteorological Satellite Program’s Operational Linescan System (DMSP/OLS) nighttime imagery. Results: NLR to be associated with a shift in the sleep habits of the general population, resulting in delayed bedtime (p<0.0001) and wake up time (p<0.0001). Overall, NLR is associated with a shortening of the sleep duration (p<0.01) and increased daytime sleepiness (p<0.0001). Exposure to greater NLR also increases the dissatisfaction with sleep quantity and quality (p<0.0001) and the likelihood of having a circadian rhythm disorder (p<0.0001). Conclusions: Outdoor nighttime light exposure is strongly associated with changes in sleep habits and impact our daytime functioning increasing the risks of excessive sleepiness. Disclosure: Dr. Ohayon has received personal compensation for activities with Jazz Pharmaceuticals and Pfizer Inc. Dr. Milesi has nothing to disclose.
L'echelle relationnelle apparait au terme de cette etude comparable a la MADRS (Depression Ra... more L'echelle relationnelle apparait au terme de cette etude comparable a la MADRS (Depression Rating Scale) en ce qui concerne la mesure de la gravite du syndrome depressif. Elle presente l'avantage d'une homogeneite plus grande et d'un pouvoir separateur meilleur en ce qui concerne les categories de patients etudies
Premiere experience de realisation d'un programme informatique capable de reproduire la demar... more Premiere experience de realisation d'un programme informatique capable de reproduire la demarche diagnostique telle qu'elle est presentee dans l'arbre de decision du DSMIII: le modele de raisonnement utilise a ete nomme ADINFER
BACKGROUND The aim of this study was to evaluate the impact of different therapy regimens, includ... more BACKGROUND The aim of this study was to evaluate the impact of different therapy regimens, including sodium oxybate (SXB)-containing regimens, on patient-reported outcomes (PROs) in people with narcolepsy. METHODS Online surveys were used to collect information from persons with narcolepsy in the Nexus Narcolepsy Registry. Surveys contained questionnaires assessing self-reported sleep quality (SQ; via single question), daytime sleepiness and function (Epworth Sleepiness Scale and Functional Outcomes of Sleep Questionnaire), health-related quality of life (HRQoL; 36-Item Short Form Health Survey [SF-36]), work productivity and impairment (Work Productivity and Activity Impairment: Specific Health Problem), and history of injuries or motor vehicle accidents. Treatment with SXB (including monotherapy or combination therapy; SXB group) was compared with non-SXB therapy (No SXB group). The P values presented are nominal, as there are no adjustments for multiplicity. RESULTS From June 2015 through December 2017, 983 participants completed 1760 surveys. SQ and daytime functioning scores were better in the SXB group compared with the No SXB group (all P < 0.001). HRQoL scores were better for the SXB group compared with the No SXB group for the SF-36 Physical Component (P = 0.016), Mental Component (P < 0.001), and all 8 subscales. Additionally, PROs were better for the SXB group for presenteeism, overall work and activity impairment, and risk of motor vehicle accidents (all P ≤ 0.001). CONCLUSION Based on participants' self-assessments, treatment regimens with SXB were associated with better outcomes than regimens not containing SXB across many PROs, including SQ, HRQoL, work and activities, and risk of traffic accidents. CLINICALTRIALS. GOV IDENTIFIER NCT02769780.
Introduction: Nonrestorative sleep (NRS) is one of the sleep disturbances that is under-appreciat... more Introduction: Nonrestorative sleep (NRS) is one of the sleep disturbances that is under-appreciated. Some studies have set its prevalence at around 10% of the general population but definitions are heterogenous. Despite its frequency, studies that paid attention to that symptom are disparate and have often taken many routes. Our aim is to examine its prevalence, its incidence and its predictive factors. Methods: The initial study was carried with 15,929 individuals from 15 US States. The longitudinal study was carried on in eight of these states. A total of 12,218 subjects were interviewed by phone during the first wave (W1) and 10,930 at the second wave (W2) three years apart. The analyses were carried on the subjects who participated in both interviews (N=10,930). NRS was assessed using a series of five questions. The global score determined the presence/absence of NRS. Results: A total of 14.7% (CI95%: 14%-15.4%) reported NRS at W1. At follow-up, 13.1% (CI95%: 12.5%-13.7%) reported NRS. The incidence per year was 2.3%. NRS was chronic in 28.9% of cases. NRS occurred alone (i.e. without any other insomnia symptoms) in 5% of the sample at W1 and 3.6% at W2. 22.2% of those with NRS alone at W1 reported other insomnia symptoms at W2. Sleep duration was at least 6h30 in 81.6% of NRS alone cases at W1 and 76.5% at W2. Daytime repercussions were reported by 66.2% of NRS alone at W1 and 52.8% at W2. NRS alone (RR: 2.4) or in combination with insomnia symptoms (RR: 3.4) was one of the strongest predictors for developing a Major Depressive Disorder at W2. Conclusion: NRS is a sleep disturbance that has some unique features that distinguish it from insomnia symptoms. Nonetheless, it can have a profound impact on daily life and can lead to further difficulties in other areas if not addressed properly.
Uploads
Papers by Maurice Ohayon