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STUDY OBJECTIVES: Excessive daytime sleepiness associated with obstructive sleep apnea affects 9%–22% of continuous positive airway pressure–treated patients. An indirect treatment comparison meta-analysis was performed to compare efficacy and safety of medications (solriamfetol, modafinil, and armodafinil) approved to treat excessive daytime sleepiness associated with obstructive sleep apnea. METHODS: Efficacy and safety measures assessed in this indirect treatment comparison included Epworth Sleepiness Scale (ESS), 20-minute Maintenance of Wakefulness Test (MWT20), Clinical Global Impression of Change (CGI-C), Functional Outcomes of Sleep Questionnaire (FOSQ), and incidence of treatment-emergent adverse events (any, serious, or leading to discontinuation). RESULTS: A systematic literature review identified 6 parallel-arm, placebo-controlled randomized controlled trials that randomized 1,714 total participants to placebo, solriamfetol, modafinil, or armodafinil. In this indirect treatment comparison, all comparators were associated with greater improvements than placebo on the ESS, MWT20, and CGI-C after 4, 8, and 12 weeks of treatment. Relative to comparators and placebo at 12 weeks, solriamfetol at 150 mg or 300 mg had the highest probabilities of improvement in the ESS, MWT20, and CGI-C. Modafinil (200 or 400 mg) and solriamfetol (150 or 300 mg) were associated with greater improvement on the FOSQ than placebo at 12 weeks. Less than 2% of patients using placebo or comparators experienced serious or discontinuation-related treatment-emergent adverse events. CONCLUSIONS: The results of this indirect treatment comparison show 12 weeks of treatment with solriamfetol, modafinil, and armodafinil resulted in varying levels of improvement on the ESS, MWT20, and CGI-C and similar safety risks in participants with excessive daytime sleepiness associated with obstructive sleep apnea. CITATION: Ronnebaum S, Bron M, Patel D, et al. Indirect treatment comparison of solriamfetol, modafinil, and armodafinil for excessive daytime sleepiness in obstructive sleep apnea. J Clin Sleep Med. 2021;17(12):2543–2555.

STUDY OBJECTIVES: Excessive daytime sleepiness (EDS) is a treatment target for many patients with obstructive sleep apnea (OSA). We aimed to understand the prevalence, risk factors, and quality of life associated with EDS in a nonclinical, “real world” sample of patients with OSA. METHODS: Cross-sectional survey of patients with OSA participating in an online peer support community, assessing demographics, comorbidities, treatment, and quality of life. Differences in those with and without EDS (Epworth Sleepiness Scale > and ≤ 10) were assessed. RESULTS: The sample (n = 422) was 54.2% male, 65.9% were ≥ 55 years, and 43.3% reported sleeping ≤ 6 hours/night. EDS was identified among 31.0% of respondents and 51.7% reported sleepiness as a precipitating factor for seeking initial OSA treatment. EDS was more prevalent in individuals reporting asthma, insomnia symptoms, positive airway pressure (PAP) use less than 6 hours/night on ≥ 5 nights/week, or sleep duration < 6 hours/night. After adjusting for demographics and comorbidities, patients with EDS reported poorer mental and physical health and well-being, lower disease-specific functional status, more activity and work impairment, and more driving impairment (P values < .05). In the subsample (n = 265) with high PAP adherence, 26.0% reported EDS, and similar associations between EDS and outcomes were observed. CONCLUSIONS: These “real world” data suggest that patients seeking online OSA support experience a high prevalence of EDS, which was associated with poorer quality of life and worse functional status. Associations persisted among respondents with high self-reported PAP-therapy adherence, potentially driving these individuals to seek online support for sleepiness-related symptoms. CITATION: Wanberg LJ, Rottapel RE, Reid ML, et al. Prevalence of sleepiness and associations with quality of life in patients with sleep apnea in an online cohort. J Clin Sleep Med. 2021;17(12):2363–2372.

STUDY OBJECTIVES: Solriamfetol, a dopamine/norepinephrine reuptake inhibitor, is approved in the United States and European Union for excessive daytime sleepiness in adults with narcolepsy (75–150 mg/day) or obstructive sleep apnea (OSA; 37.5–150 mg/day). In 12-week studies, solriamfetol was associated with improvements in quality of life in participants with narcolepsy or OSA. These analyses evaluated the long-term effects of solriamfetol on quality of life. METHODS: Participants with narcolepsy or OSA who completed previous solriamfetol studies were eligible. A 2-week titration was followed by a maintenance phase ≤ 50 weeks (stable doses: 75, 150, or 300 mg/day). Quality of life assessments included Functional Outcomes of Sleep Questionnaire short version, Work Productivity and Activity Impairment Questionnaire: Specific Health Problem, and 36-Item Short Form Health Survey version 2. Mean (standard deviation) changes from baseline to end of study were evaluated. Data were summarized descriptively. Adverse events were assessed. RESULTS: Safety population comprised 643 participants (417 OSA, 226 narcolepsy). Solriamfetol improved Functional Outcomes of Sleep Questionnaire short version Total scores (mean change [standard deviation], 3.7 [3.0]) and 36-Item Short Form Health Survey version 2 Physical and Mental Component Summary scores (3.1 [6.9] and 4.3 [8.4], respectively); improvements were sustained throughout treatment. On Work Productivity and Activity Impairment Questionnaire: Specific Health Problem, solriamfetol reduced (improved) % presenteeism, % overall work impairment, and % activity impairment by a minimum of 25%. Common adverse events (≥ 5%): headache, nausea, nasopharyngitis, insomnia, dry mouth, anxiety, decreased appetite, and upper respiratory tract infection. CONCLUSIONS: Long-term solriamfetol treatment was associated with clinically meaningful, sustained improvements in functional status, work productivity, and quality of life for up to 52 weeks. Adverse events were similar between narcolepsy and OSA. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: A Long-Term Safety Study of JZP-110 in the Treatment of Excessive Sleepiness in Subjects with Narcolepsy or OSA; Identifier: NCT02348632; URL: https://clinicaltrials.gov/ct2/show/NCT02348632 CITATION: Weaver TE, Pepin J-L, Schwab R, et al. Long-term effects of solriamfetol on quality of life and work productivity in participants with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea. J Clin Sleep Med. 2021;17(10):1995–2007.

Rimal Bera,1 Morgan Bron,2 Betsy Benning,3 Samantha Cicero,4 Heintje Calara,2 Diane Darling,2 Ericha Franey,2 Kendra Martello,5 Charles Yonan2 1Irvine Medical Center, University of California, Orange, CA, USA; 2Health Economics and Outcomes Research, Neurocrine Biosciences, Inc., San Diego, CA, USA; 3Emerging Biopharma, IQVIA Inc., Danbury, CT, USA; 4Field Medical Affairs, Neurocrine Biosciences, Inc., San Diego, CA, USA; 5Public Policy, Neurocrine Biosciences, Inc., San Diego, CA, USACorrespondence: Rimal Bera, Irvine Medical Center, University of California, 101 City Drive, Orange, CA, 92618, USA, Tel +1-714-456-6898, Fax +1-714-456-5112, Email rbera@hs.uci.eduPurpose: Tardive dyskinesia (TD) is a drug-induced movement disorder (DIMD) seen in patients taking dopamine-receptor blocking agents (DRBAs). Clinicians should regularly monitor patients with or at risk of developing DIMDs; however, telehealth visits during the COVID-19 pandemic presented several significant challenges related to screening and care of these patients. In this observational survey study, respondents compared in-person with video/telephone visits to determine the impact on the evaluation, diagnosis, and monitoring of patients with DIMDs.Methods: The online survey was conducted (May 14–June 21, 2021) with qualified clinicians who prescribed a vesicular monoamine transporter 2 inhibitor or benztropine for DIMDs in the past 6 months, spent ≤ 70% of their professional time in the clinic, and conducted telehealth visits with ≥ 15% of their patients between December 2020 and January 2021. The questionnaire probed clinicians about their ability to evaluate, diagnose and monitor (hereinafter referred to as manage) patients with DIMDs via telehealth.Results: Survey respondents included 277 clinicians from psychiatry (n = 168) and neurology (n = 109) practices. Certain signs and symptoms (visual cues) used for diagnosis of DIMDs were not observable through telehealth and evaluation was comparatively more difficult with phone visits than video visits. Patients without caregivers and lower-functioning patients were at higher risk of missed diagnosis of DIMDs and were also difficult to monitor via telehealth. Limited access to computers or telephones and patients living alone were among the top socioeconomic barriers limiting clinicians’ ability to diagnose DIMDs. Patients without a regular caregiver were also more difficult for clinicians to evaluate and monitor adequately. Further, most clinicians received no training related to evaluation of DIMDs via telehealth or engaging caregivers as health care partners.Conclusion: Our study highlights specific limitations and challenges and provides considerations to help clinicians better manage DIMDs in the context of telehealth services.Keywords: telemental health, telemedicine, psychiatry, caregiver, neurology, training

To evaluate the clinical relevance of solriamfetol in treating excessive daytime sleepiness in participants with narcolepsy or obstructive sleep apnea (OSA).This posthoc analysis includes data from two 12-week, randomized phase 3 studies in participants with narcolepsy or OSA treated with once-daily placebo or solriamfetol 37.5 mg (OSA only), 75 mg, 150 mg, or 300 mg. Excessive daytime sleepiness was assessed with the Epworth Sleepiness Scale (ESS) at baseline and at week 12. Cumulative distribution function plots were generated using a last-observation-carried-forward approach to determine the percentage of participants who achieved ESS scores ≤ 10, within the normal range, and the percentage who achieved a reduction (improvement) in ESS ≥ 25% relative to baseline. Safety was also assessed.In narcolepsy (n = 231), 30.5%-49.2% of participants treated with solriamfetol (across doses) reported ESS scores ≤ 10 and 44.1%-62.7% achieved a ≥ 25% decrease from baseline in ESS scores at week 12, compared with 15.5% and 27.6%, respectively, of placebo recipients. In OSA (n = 459), 51.8%-73.0% of participants treated with solriamfetol (across doses) reported ESS scores ≤ 10 and 50.0%-81.9% achieved a ≥ 25% decrease from baseline in ESS scores at week 12, compared with 37.7% and 36.8%, respectively, of placebo recipients. Results were generally dose-dependent, with more responders at higher solriamfetol doses. Common treatment-emergent adverse events (≥ 5% of solriamfetol recipients in either study) were headache, nausea, decreased appetite, nasopharyngitis, dry mouth, and anxiety.A greater percentage of participants treated with solriamfetol achieved normal ESS scores (≤ 10) or clinically meaningful improvements on the ESS compared with those receiving placebo. The safety profile was similar between participants with narcolepsy and those with OSA.Registry: ClinicalTrials.gov. Names: TONES 2 and TONES 3. URLs: https://www.clinicaltrials.gov/ct2/show/NCT02348593 and https://www.clinicaltrials.gov/ct2/show/NCT02348606. Identifiers: NCT02348593, NCT02348606. Registry: European Union Drug Regulating Authorities Clinical Trials. Names: TONES 2 and TONES 3. URL: https://www.eudract.ema.europa.eu. Identifiers: EudraCT 2014-005487-15, EudraCT 2014-005514-31.

Purpose This study estimated thresholds for clinically important responses and minimally important differences for two indicators of improvement for the 10-item version of the functional outcomes of sleep questionnaire (FOSQ-10). Methods Participants with excessive daytime sleepiness with narcolepsy or obstructive sleep apnea received 12 weeks of solriamfetol treatment. Participants completed the FOSQ-10 and other patient-reported outcome measures, including the single-item patient global impression of change (PGI-C) assessment. Clinicians completed the single-item clinician global impression of change (CGI-C) for each participant. Data from the two studies were analyzed separately, both without regard to treatment assignment. In total, 690 participants (47% female, mean age 48 years, 77% Caucasian, 91% from North America) were enrolled. Two clinically important changes, defined as a minimally important difference and a clinically important response, were determined using distribution and anchor-based analyses. A receiver operating characteristic analysis was used to determine the optimal FOSQ-10 change threshold. Results Spearman correlations between change in FOSQ-10 scores and PGI-C and CGI-C were − 0.57 and − 0.49 for participants with narcolepsy and − 0.42 and − 0.37 for participants with obstructive sleep apnea. Receiver operating characteristic analysis suggested minimally important difference and clinically important response estimates of 1.7 and 2.5 and 1.8 and 2.2 points in narcolepsy and obstructive sleep apnea, respectively. Conclusions Minimally important difference and clinically important response estimates for the FOSQ-10 for adults with excessive daytime sleepiness in narcolepsy or obstructive sleep apnea will be helpful for interpreting changes over time and defining a clinical responder. ClinicalTrials.gov identifiers NCT02348593 (first submitted January 15, 2015) and NCT02348606 (first submitted January 15, 2015)

STUDY OBJECTIVES: The primary objective was to describe trends in the 2-year limited duration prevalence of narcolepsy from 2013–2016 in a large insured population with claims activity. Secondary objectives were to assess the prevalence of other sleep disorders and the frequency of diagnostic sleep testing. METHODS: Nationwide medical/prescription claims (Symphony Health) were analyzed to estimate the annual prevalence per 100,000 persons of narcolepsy and other sleep disorders (obstructive sleep apnea, idiopathic hypersomnia, rapid eye movement sleep behavior disorder, periodic limb movement disorder) and the frequency of diagnostic sleep testing. Prevalence was adjusted to the age/sex distribution of the 2016 US census estimates. RESULTS: The prevalence of narcolepsy per 100,000 persons increased 14% from 38.9 in 2013 to 44.3 in 2016. Obstructive sleep apnea prevalence increased 41% over the study period from 2,429 to 3,420 per 100,000. Large increases in prevalence were also seen for idiopathic hypersomnia (32%), periodic limb movement disorder (30%), and rapid eye movement sleep behavior disorder (64%). For each sleep disorder, prevalence was higher for those with commercial insurance versus Medicare/Medicaid, and markedly lower prevalence was observed for the Northeast compared with the Midwest, South, and Western US regions. The frequency of multiple sleep latency/maintenance of wakefulness testing declined by 20%, and polysomnography declined by 15%. Conversely, home sleep apnea testing increased by 117%. CONCLUSIONS: The prevalence of narcolepsy, obstructive sleep apnea, and the other sleep disorders increased appreciably over the 2013–2016 period. It remains to be determined whether the trends seen in our analyses are due to increased incidence or increased awareness of these conditions. CITATION: Acquavella J, Mehra R, Bron M, Suomi JM-H, Hess GP. Prevalence of narcolepsy, other sleep disorders, and diagnostic tests from 2013–2016: insured patients actively seeking care. J Clin Sleep Med. 2020;16(8):1255–1263.

Rationale: Excessive daytime sleepiness in patients with obstructive sleep apnea is associated with substantial burden of illness. Objectives: To assess treatment effects of solriamfetol, a dopamine/norepinephrine reuptake inhibitor, on daily functioning, health-related quality of life, and work productivity in participants with obstructive sleep apnea and excessive daytime sleepiness as additional outcomes in a 12-week phase 3 trial (www.clinicaltrials.gov identifier NCT02348606). Methods: Participants (N = 476) were randomized to solriamfetol 37.5, 75, 150, or 300 mg or to placebo. Outcome measures included the Functional Outcomes of Sleep Questionnaire short version, Work Productivity and Activity Impairment Questionnaire: Specific Health Problem, and 36-item Short Form Health Survey version 2. A mixed-effects model with repeated measures was used for comparisons with placebo. Results: Demographics, baseline disease characteristics, daily functioning, health-related quality of life, and work productivity were similar across groups. At Week 12, increased functioning and decreased impairment were observed with solriamfetol 150 and 300 mg (mean difference from placebo [95% confidence interval]) on the basis of Functional Outcomes of Sleep Questionnaire total score (1.22 [0.57 to 1.88] and 1.47 [0.80 to 2.13], respectively), overall work impairment (−11.67 [−19.66 to −3.69] and −11.75 [−19.93 to −3.57], respectively), activity impairment (−10.42 [−16.37 to −4.47] and −10.51 [−16.59 to −4.43], respectively), physical component summary (2.07 [0.42 to 3.72] and 1.91 [0.22 to 3.59], respectively), and mental component summary (150 mg only, 2.05 [0.14 to 3.96]). Common adverse events were headache, nausea, decreased appetite, and anxiety. Conclusions: Solriamfetol improved measures of functioning, quality of life, and work productivity in participants with obstructive sleep apnea and excessive daytime sleepiness. Safety was consistent with previous studies. Clinical trial registered with www.clinicaltrials.gov (NCT02348606).

Background: The prevalence of obstructive sleep apnea (OSA) has not been assessed within the United States (US) in over adecade. Objectives:From 2013 to 2016, we calculated annual 2-year limited duration prevalence of diagnosed OSA in a large (~66million), geographically diverse insured population. We evaluated trends by age and sex; and assessed positive airway pressure (PAP) use and excessive sleepiness (hypersomnia diagnosis, or prescriptions for stimulant or wake-promoting agent [WPA]). Methods:Overall and age/sex specific prevalence per 100 insured persons was calculated on an annual basis. The cohort was defined to include those with medical and pharmacy claims activity. To mitigate rule-out diagnoses,cases had to have ≥2 medical claims for OSA within a 6-month period. Overall annual prevalences were directly standardized to the US population using 2016 US age and sex Census weights. Results: Annualage/sex adjusted prevalence of OSA increased from 2.4% in 2013 to 3.4% in 2016. OSA patients had a mean age of 58 years and there was a ≈2:1 male:female prevalence ratio. OSA patients with PAP claims increased from 42.2% to 44.1% over the study period. Excessive sleepiness (hypersomnia or stimulant/WPA prescriptions) for patients with or without PAP use both declined by ≈ 4% -5%. Conclusions:Diagnosed OSA prevalence and PAP use among insured members with claims activity increased during 2013-2016 while clinical markers of excessive sleepiness declined. Males had a much higher prevalence of OSA than females.

Background Obstructive sleep apnea (OSA) is associated with excessive daytime sleepiness (EDS), which may go undiagnosed and can significantly impair a patient’s health-related quality of life (HRQOL). This qualitative research examined timing and reasons patients sought medical care for their EDS and OSA symptoms, and the impact of EDS on HRQOL. Methods Focus groups were conducted in 3 US cities with 42 participants currently experiencing EDS with OSA. Transcripts were coded and analyzed using an adapted grounded theory approach common to qualitative research. Results Over three-fifths of study participants (n = 26, 62%) were currently using a positive airway pressure (PAP) or dental device; one-third (n = 14, 33%) had previously used a positive airway pressure (PAP) or dental device, and the remainder had either used another treatment (n = 1, 2%) or were treatment naïve (n = 1, 2%). Twenty-two participants (52%) reported experiencing OSA symptoms for ≥1 year, with an average duration of 11.4 (median 8.0, range 1–37) years before seeking medical attention. Several (n = 7, 32%) considered their symptoms to be “normal,” rather than signaling a serious medical condition. Thirty participants (71%) discussed their reasons for ultimately seeking medical attention, which included: input from spouse/partner, another family member, or friend (n = 20, 67%); their own concern about particular symptoms (n = 7, 23%); and/or falling asleep while driving (n = 5, 17%). For all 42 participants, HRQOL domains impacted by EDS included: physical health and functioning (n = 40, 95%); work productivity (n = 38, 90%); daily life functioning (n = 39, 93%); cognition (n = 38, 90%); social life/relationships (n = 37, 88%); and emotions (n = 30, 71%). Conclusions Findings suggest that patients may be unaware that their symptoms could indicate OSA requiring evaluation and treatment. Even following diagnosis, EDS associated with OSA can continue to substantially affect HRQOL and daily functioning. Further research is needed to address diagnostic delays and unmet treatment needs for patients with EDS associated with OSA.

Objective To evaluate the association between obstructive sleep apnea (OSA) and risk of motor vehicle accident (MVA). Methods We conducted a cohort study at Kaiser Permanente Washington using electronic health plan data and linked Washington State Department of Transportation MVA records. We included persons 18–79 years of age during 2005–2014. OSA was ascertained via diagnosis codes. The primary outcome, first MVA during cohort follow-up, was ascertained from state MVA records. Risk factors for MVAs, including medical conditions and medication use, were ascertained from health plan data. Multivariable Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI) for the association between OSA and study outcomes. Results Among the 879,547 eligible persons, the unadjusted rate of MVA in those with and without OSA was 238 and 229 per 10,000 person-years, respectively. A diagnosis of OSA was associated with a 17% increased risk of MVA (adjusted HR = 1.17; 95% CI: 1.13 to 1.20). Conclusion In this large population-based study, a diagnosis of OSA was associated with a modestly increased risk of MVA.

IntroductionAs a result of COVID-19, patients and clinicians rapidly shifted to telehealth. An observational survey study, Real-World Tele-Health Evaluation of Tardive Dyskinesia (TD) Symptoms Communication/Observation Procedure Evaluation in Outpatient Clinical Settings (TeleSCOPE), was conducted to better understand how this shift affected the evaluation of drug-induced movement disorders (DIMDs), including TD.MethodsTwenty-minute online quantitative surveys were conducted with neurology and psychiatry specialists (physicians and advanced practice providers) who met the following criteria: ≥3 years of practice with ≥70% of time spent in a clinic; prescribed a vesicular monoamine transporter 2 (VMAT2) inhibitor or benztropine for DIMD at least once in the past 6 months; and conducted telehealth visits with ≥15% of their patients from December 2020 to January 2021.ResultsRespondents included 277 clinicians (neurology = 109, psychiatry = 168). Telehealth visits increased after COVID-19, with significantly greater increases in psychiatry vs neurology: phone (38% vs 21%); video (49% vs 42%). Across both specialties, top drivers/prompts for further DIMD evaluation were as follows: mention of tics or movements by family members or others (86%); trouble with gait, falls, walking, or standing (82%); difficulty swallowing or eating (74%); and difficulty writing, using phone, computer (71%). However, in the 6 months prior to June 2021, virtual evaluation, diagnosis, and monitoring of patients were challenging. For both specialties, many at-risk patients (ie, taking a dopamine receptor blocking agent) were not evaluated for DIMDs via video-based visits (psychiatry = 45%, neurology = 70%) or phone-only visits (psychiatry = 76%, neurology = 91%). Clinicians listed evaluation of gait/falls/walking/standing as the most challenging aspect of virtual assessment for phone-only visits (psychiatry = 53%, neurology = 57%) and video-based visits (psychiatry = 26%, neurology = 31%). Additional challenges included limited access to computers, insufficient training for clinicians and staff, and greater difficulty obtaining reimbursements (especially for complex telehealth visits). Patients without a participating caregiver, along with lower functioning patients, were at the highest risk of a missed DIMD diagnosis.ConclusionsDuring the COVID-19 pandemic, telehealth significantly reduced clinicians’ ability or willingness to evaluate, diagnose, and monitor DIMDs. Clinicians stated multiple factors increased the risk of a missed or incorrect diagnosis. Challenges to optimal telehealth effectiveness included lack of patient access to computers, need for more clinician/staff training, lack of awareness of coverage, need for sufficient fee reimbursement. In-person evaluation continues to be the gold standard for assessing and treating DIMDs. However, if telehealth is necessary, the use of specific questions and directions is recommended for better communication and more accurate assessments.FundingNeurocrine Biosciences, Inc.

This study examined the correlation between improvements in excessive daytime sleepiness in participants with obstructive sleep apnea or narcolepsy and changes in functional status, work productivity and health‐related quality of life. Data from two 12‐week randomized controlled trials of solriamfetol were analyzed. Participants completed the Epworth Sleepiness Scale, 10‐item Functional Outcomes of Sleep Questionnaire, Work Productivity and Activity Impairment questionnaire and 36‐Item Short Form Health Survey and performed the Maintenance of Wakefulness Test at baseline and weeks 4, 8 and 12. Patient Global Impression of Change was assessed at weeks 4, 8 and 12. Pearson correlations were calculated for change in scores from baseline to week 12. For both studies, changes in the 10‐item Functional Outcomes of Sleep Questionnaire were highly correlated (absolute value >0.5) with changes in Epworth Sleepiness Scale scores; changes in multiple domain scores of the 36‐Item Short Form Health Survey and Work Productivity and Activity Impairment questionnaire were moderately correlated (0.3–0.5) with changes in Epworth Sleepiness Scale scores in both studies and highly correlated for participants with narcolepsy. Changes in Maintenance of Wakefulness Test scores correlated moderately with changes in Epworth Sleepiness Scale scores in both studies. At week 12, Patient Global Impression of Change ratings correlated highly with Epworth Sleepiness Scale and 10‐item Functional Outcomes of Sleep Questionnaire scores for both disorders. Other correlations were low. Self‐reported assessments of sleepiness and global improvement appear to be more strongly correlated with measures of functioning and health‐related quality of life than objectively assessed sleepiness.

Background: Obstructive sleep apnea (OSA) with excessive daytime sleepiness (EDS) can impair quality of life (QOL) and may go undiagnosed. Objectives: To examine the diagnosis experience and impacts of EDS with OSA on QOL in the US. Methods: Focus groups in 3 US cities with 42 patients experiencing EDS with OSA; coded transcripts qualitatively analysed using adapted grounded theory approach. Results: Prior to diagnosis, 40% (n=17) of patients were aware of their EDS and 74% (n=31) were informed of their other OSA symptoms by a spouse/partner, family or friends. About half (n=22, 52%) waited an average of 11.4 (range 1-37) years to seek medical care for OSA; 32% (n=7/22) had thought their symptoms were normal rather than a sign of OSA. Reasons for seeking care were: input from a loved one (n=21, 50%); self-concern about symptoms (n=7, 17%); and impaired driving (n=5, 12%). Twenty-seven patients discussed referral pathways: 15/27 (56%) first saw a primary care physician and 12/27 (44%) a specialist. Although 74% (n=31) were currently on OSA treatment, the majority reported EDS impacts on physical functioning (n=40, 95%); daily life (n=39, 93%); cognition (n=38, 90%); social life (n=37, 88%); and work (n=29, 69%). Conclusions: In the US, OSA diagnosis is often delayed, with many patients unaware of the need to seek medical care. Following OSA diagnosis, EDS may continue to impair QOL. Future research should address diagnostic delays and unmet treatment needs for this population.

Introduction Adverse events and complications limit the long-term use of current antidiabetic treatment options for patients with type 2 diabetes mellitus (T2DM), particularly for older adults who are often receiving therapy for other comorbid conditions. The aim of this study was to evaluate the benefits of the dipeptidyl peptidase-4 inhibitor, alogliptin, versus glipizide, a sulfonylurea, in achieving glycemic control without the risk of hypoglycemia, weight gain, or both in older patients with T2DM. Methods This was an exploratory, post hoc analysis of a global, multicenter, randomized, double-blind, active-controlled study comparing alogliptin and glipizide. Patients (n = 441) aged 65–90 years with glycosylated hemoglobin (HbA1c) 6.5–9.0% who failed on diet and exercise alone or who had inadequately controlled T2DM despite oral antidiabetic monotherapy were recruited from 110 sites across 15 countries. Alogliptin 25 mg (n = 222) or glipizide 5 mg up-titrated to 10 mg (n = 219) was administered once daily for 52 weeks. Composite endpoints of HbA1c ≤7.0% coupled with the absence of hypoglycemia and weight gain, or an HbA1c reduction of ≥0.5% in the absence of hypoglycemia and weight gain, were then measured. Results In the primary analysis, least squares mean HbA1c changes from baseline to Week 52 were similar in both the alogliptin and glipizide groups. The proportion of patients achieving HbA1c ≤7.0% without hypoglycemia or weight gain was significantly higher for alogliptin versus glipizide (24% vs 13%, p

The objectives of this study were to assess and compare all-cause mortality rates between pioglitazone (PIO) and insulin (INS).The study population included 56,536 patients with type 2 diabetes aged ≥45 years who were first-time users of PIO or INS. Data from 1 May 2000 until 30 June 2010 from the i3 InVision Data Mart database were linked to death records of the US Social Security Administration obtained in March 2012, with approval from the Institutional Review Board and in full compliance with the Health Insurance Portability and Accountability Act of 1996.Kaplan-Meier curves were generated and hazard ratios (HRs) were estimated for the occurrence of deaths in the PIO and INS cohorts using Cox proportional hazards models adjusted with inverse probability weights derived from propensity scores.After adjustment for40 covariates through inverse probability weights derived from propensity scores, the PIO group showed a significantly lower risk of all-cause mortality (HR 0.33; 95% confidence interval, 0.31, 0.36). The risk of all-cause mortality was also significantly lower in the PIO cohort than the INS cohort among subgroups based on baseline variables such as sex, age (55 years, ≥55 years), antidiabetic medication use (sulfonylureas or metformin), lipid-altering medication use, and congestive heart failure status. The study has some limitations. Use of a claims database means a potential bias toward a younger cohort. Disease-specific mortality was not identified because of no recorded cause of death. Reliable information regarding the differences in disease deterioration rate and some clinical and lab results were not available, which limits the statistical adjustment of baseline variables.PIO was associated with a lower risk of all-cause mortality than INS.

To describe the distribution of costs and to identify the drivers of high costs among adult patients with type 2 diabetes mellitus (T2DM) receiving oral hypoglycemic agents.T2DM patients using oral hypoglycemic agents and having HbA1c test data were identified from the Truven MarketScan databases of Commercial and Medicare Supplemental insurance claims (2004-2010). All-cause and diabetes-related annual direct healthcare costs were measured and reported by cost components. The 25% most costly patients in the study sample were defined as high-cost patients. Drivers of high costs were identified in multivariate logistic regressions.Total 1-year all-cause costs for the 4104 study patients were $55,599,311 (mean cost per patient = $13,548). Diabetes-related costs accounted for 33.8% of all-cause costs (mean cost per patient = $4583). Medical service costs accounted for the majority of all-cause and diabetes-related total costs (63.7% and 59.5%, respectively), with a minority of patients incurring80% of these costs (23.5% and 14.7%, respectively). Within the medical claims, inpatient admission for diabetes-complications was the strongest cost driver for both all-cause (OR = 13.5, 95% CI = 8.1-23.6) and diabetes-related costs (OR = 9.7, 95% CI = 6.3-15.1), with macrovascular complications accounting for most inpatient admissions. Other cost drivers included heavier hypoglycemic agent use, diabetes complications, and chronic diseases.The study reports a conservative estimate for the relative share of diabetes-related costs relative to total cost. The findings of this study apply mainly to T2DM patients under 65 years of age.Among the T2DM patients receiving oral hypoglycemic agents, 23.5% of patients incurred 80% of the all-cause healthcare costs, with these costs being driven by inpatient admissions, complications of diabetes, and chronic diseases. Interventions targeting inpatient admissions and/or complications of diabetes may contribute to the decrease of the diabetes economic burden.

The American Diabetes Association and European Association for the Study of Diabetes issued a new patient-centered approach for the management of hyperglycemia in patients with Type 2 diabetes. With a focus on older adults and the elderly, the authors explored the alignment of elements of the suggested framework with patients' reports of receiving combination or monotherapy using US national survey data (National Health and Nutrition Examination Survey 2001-2010) and a physician survey. Combination therapy was positively associated with age (range: 1.56-1.63; p = 0.04-0.07), obesity (odds ratio [OR]: 1.40; p = 0.01), HbA(1c) ≥7.0 (OR: 2.00; p0.01), number of years of living with diabetes (OR: 1.02 per year; p = 0.01) and hyperlipidemia (OR: 1.36; p = 0.02). An interaction term between years of living with diabetes and comorbidities1 pointed to a trend of those with comorbidities1 to be less probable to report combination therapy (OR: 0.98; p = 0.07) per additional year of diabetes history. Results suggest that sicker, older patients might benefit from more aggressive therapy, in the context of diabetes prevalence, this is expected to continue rising in that population.

Current type 2 diabetes mellitus (T2DM) treatment involves progressive interventions from lifestyle changes to pharmacological therapies. Previous studies found that combination therapy with a dipeptidyl peptidase-4 inhibitor (DPP-4i) and pioglitazone (PIO) is more effective than monotherapies in treating poorly controlled T2DM, but there is no consensus on whether these drugs should be initiated at the same time (initial combination therapy) or sequentially. We aimed to assess glycemic control with initial versus sequential combination therapy with PIO and a DPP-4i in patients with glycosylated hemoglobin (HbA1c) levels ≥ 7%. A retrospective chart review was conducted on T2DM patients from diverse geographic sites in the United States initiating therapies from March 2, 2010 to February 28, 2011. Patients were selected for initial combination therapy, if starting PIO and a DPP-4i within 30 days of each other, or sequential combination therapy, if first taking PIO alone for ≥ 60 days before adding a DPP-4i within 1 year of PIO initiation. The HbA1c level reduction from baseline was compared between cohorts using linear regression models adjusting for demographics, baseline HbA1c, T2DM duration, comorbidities, and various medications. There were 250 patients in the initial and 211 in the sequential combination therapy cohorts; 57.3% were male, 65.3% were Caucasian, and the mean age was 54.3 years. Patients receiving initial combination therapy had a significantly higher mean baseline HbA1c level (8.6% vs 8.0%, P < 0.0001), a higher prevalence of coronary artery disease (11.6% vs 6.2%, P = 0.0430), and a lower prevalence of hyperlipidemia (56.4% vs 67.8%, P = 0.0120) and of hypertension (62.4% vs 72.0%, P = 0.0290), compared with the sequential therapy cohort. In adjusted analyses, initial combination therapy was associated with a significantly greater reduction in HbA1c levels than sequential combination therapy at months 12, 16, and 20 (-0.977 vs -0.819, P = 0.034; -1.453 vs -1.242, P = 0.048; and -1.182 vs -0.810, P = 0.013, respectively). Our findings suggest initial combination therapy may be the preferred option in choosing combination therapies.

To investigate the rate and impact of hypoglycemic events among patients with type 2 diabetes mellitus (T2DM) receiving different classes of oral antidiabetic drugs (OADs).Adult patients with T2DM were extracted from the Ingenix IMPACT claims database. The mean number of health care visits due to hypoglycemic events per patient-year was estimated. Multivariate regression models were used to: 1) assess the risk factors for experiencing a hypoglycemic event; 2) assess the effect of experiencing hypoglycemic events on antidiabetic treatment discontinuation; and 3) compare 12-month post-index date costs between patients with and without hypoglycemic events.212 061 patients with T2DM were included in the analysis. The estimated frequency of hypoglycemia-related health care visits was 0.054 per patient-year. Insulin use was associated with increased risk of developing hypoglycemia, followed by use of sulfonylureas and other OADs (eg, meglitinide and α-glucosidase inhibitors). The impacts of thiazolidinediones, metformin, and dipeptidyl peptidase-4 on hypoglycemia risk were relatively small. Having a hypoglycemic event was associated with significantly increased risk of antidiabetic treatment discontinuation. Patients with hypoglycemia showed significantly higher annual all-cause and diabetes-related health care costs than patients without hypoglycemia (adjusted Δ = +$5024 and +$3747, respectively; both P0.0001).Different OAD classes were associated with different levels of risk for hypoglycemic events. Hypoglycemia was associated with a higher risk of antidiabetic treatment discontinuation and significantly increased health care costs.

To compare glycemic goal achievement (HbA(1c) 7%) in type 2 diabetes patients receiving initial metformin plus pioglitazone combination therapy and initial metformin monotherapy augmented with pioglitazone in a cohort follow-up study.Adult patients were identified from the Ingenix Impact database (01/01/99-03/31/07). Qualified patients had a baseline HbA(1c) ≥ 7%; a second laboratory value within 9 months; no other anti-diabetic prescriptions 6 months before or 30 days after treatment initiation; and continuous enrollment during baseline. The index date was the date on which the second medication was initiated. Goal achievement was compared independently at 6, 12 and 18 months using a chi-square test. Logistic regression was used to control for baseline differences. Last observation carried forward was used to impute missing HbA(1c) values. Sub-group analysis was conducted on patients with baseline HbA(1c) values between 7% and 9%, and9%.The proportion of patients achieving glycemic goal at each specified time point.A total of 179 patients received initial combination therapy and 347 patients received sequential therapy. A greater proportion of initial combination patients achieved the glycemic goal compared to sequential patients at months 6, 12 and 18 (66.5 vs. 49.6%; 65.9 vs. 48.1%; 65.9 vs. 48.4%, respectively; p 0.001 for all). Logistic regression confirmed these findings (odds ratios [OR]: 3.18-3.31). Sub-group analysis showed a more pronounced advantage for aggressive initial combination treatment among patients with HbA(1c) 9% (OR: 5.39-6.04) than among patients with HbA(1c) between 7% and 9% (OR: 2.28-2.79).Initial combination therapy patients are more likely to achieve glycemic control than sequential therapy patients, especially for patients with baseline HbA(1c) 9%. This study is limited by the relatively small sample size and the frequency of HbA(1c) reporting. Future research could examine goal achievement using a larger sample and more complete laboratory data to confirm these findings.

Research suggests high rates of discontinuation of selective serotonin reuptake inhibitors (SSRIs).The aim of this study was to compare the rates of first refill for sertraline, paroxetine, and citalopram, the 3 most commonly used SSRIs that were under patent protection at the time of the study. SSRIs that were available in generic formulations in this period were not included in the analysis because prescribing patterns and compliance rates for generic products may differ from those of branded products.This analysis was conducted using claims data from an administrative database. Claims from January 1, 1999, through June 30, 2002, were analyzed. Adults aged 18 to 64 years with a diagnosis of depression, posttraumatic stress disorder, or social anxiety disorder who had initiated one of the SSRIs of interest during this period were included in the analysis. Refill status was determined based on a refill of the SSRI prescription within 1.5 times the days' supply dispensed or 15 days after the dispensing date of the index SSRI. To adjust for the effects of confounding factors, we conducted a multivariate logistic regression on the status of the first refill. The covariates included age (continuous variable), sex, index drugs (with sertraline as the reference group), and a dummy variable for copayment15 dollars.Recipients of sertraline (n=5590) or citalopram (n=4124) were more likely than recipients of paroxetine (n=5201) to refill their original prescriptions (refill rate, 54.70%, 54.49%, and 50.99%, respectively; both comparisons, P0.001). In the logistic regression, the effects of age, sex, and copayment were not significant.This study found that the likelihood of refilling the first prescription varied by SSRI. In the population studied, patients were significantly more likely to refill the first prescription for sertraline or citalopram than the first prescription for paroxetine.

Background: Previous attempts to improve anti-depressant adherence have achieved mixed results. The current study evaluated the effectiveness of a patient education intervention designed to increase adherence to sertraline treatment. Method: Data from a national pharmacy claims database were used to retrospectively match (along key demographic and clinical variables) consecutive patients prescribed sertraline (N = 1462) who received an educational intervention (Knowing More) between May 1, 2003, and April 30, 2004, with a control group of concurrent sertraline-treated patients who did not receive the intervention (N = 1462). The intervention consisted of 10 newsletters distributed over a 9-month period by mail and e-mail. The intervention and control groups were compared over a 7-month follow-up period on 3 adherence measures: time to discontinuation, days on therapy, and percentage of days on therapy. Results: Cox regression analysis revealed that the time to discontinuation of sertraline (median = 100 days) was significantly greater (p < .0001) for the intervention group compared with the control group (median = 60 days). By the end of the follow-up period, 27% of patients remained on therapy with Knowing More versus 15% of those not enrolled in the compliance program. The mean number of days on therapy was 24.8 days (25.5%) longer for the intervention group compared with the control group (122.5 days for the intervention group versus 97.7 days for the control group). The percentage of days on therapy was 88.2% for the intervention group versus 77.7% for the control group among patients with at least 1 refill prescription (p < .001). Conclusion: The educational compliance intervention, Knowing More, was associated with a significant increase in adherence to antidepressant treatment.

Background Diabetes is an important global disease, associated with significant morbidity and an increased risk of death due to chronic end-organ complications. The thiazolidinediones, used mainly as third-line agents in type 2 diabetes mellitus (T2DM), have been associated with some safety concerns, such as an increased risk of bladder cancer, an increased risk of bone fracture and heterogeneous effects on cardiovascular events. Objective This study aimed to evaluate safety data on pioglitazone for several outcomes and examine them in context with each other as well as with insulin, another third-line treatment for T2DM. Methods This retrospective cohort study extracted data from May 1, 2000 until June 30, 2010, from the i3 InVision Data Mart™ database. To adjust for the testing of multiple hypotheses, the Holm method was applied to endpoints representing potential harm from pioglitazone treatment, separately from those representing potential benefit from pioglitazone. The study population included patients with T2DM ≥ 45 years old who were new users of either pioglitazone or insulin. Key outcomes were incident cases of a composite of myocardial infarction (MI) or stroke requiring hospitalization; bone fracture requiring hospitalization; bladder cancer; and a composite of nine other selected cancers. Kaplan–Meier curves were generated and hazard ratios (HRs) for pioglitazone versus insulin were estimated from Cox proportional hazards models adjusted with inverse probability of treatment weights derived from propensity scores. Results A total of 56,536 patients (pioglitazone group 38,588; insulin group 17,948) qualified for the study. The mean follow-up was 2.2 years for pioglitazone and 1.9 years for insulin patients. Weighted survival analysis of the composite of MI and stroke, as well as the composite of nine cancers, yielded significant differences in favour of pioglitazone. For the composite of MI and stroke, the HR for pioglitazone versus insulin was 0.44 (95 % confidence interval [CI] 0.39–0.50, p