Relationship between sleep efficacy endpoints and measures of functional status and health-related quality of life in participants with narcolepsy or obstructive sleep apnea treated for excessive daytime sleepiness.

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.

Determination of thresholds for minimally important difference and clinically important response on the functional outcomes of sleep questionnaire short version in adults with narcolepsy or obstructive sleep apnea.

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).

Understanding the burden of illness of excessive daytime sleepiness associated with obstructive sleep apnea: a qualitative study.

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.

The Tardive Dyskinesia Impact Scale (TDIS), a novel patient-reported outcome measure in tardive dyskinesia: development and psychometric validation.

BACKGROUND: Tardive dyskinesia (TD), a movement disorder in which patients experience abnormal involuntary movements, can have profound negative impacts on physical, cognitive, and psychosocial functioning. The Abnormal Involuntary Movement Scale (AIMS), a clinician-rated outcome, is considered the gold standard for evaluating treatment efficacy in TD clinical trials. However, it provides little information about the impacts of uncontrolled movements from a patient perspective and can be cumbersome to administer in clinical settings. The Tardive Dyskinesia Impact Scale (TDIS) was developed as a patient-reported outcome measure to fulfill the need for a disease-specific impact assessment in TD. The objective of the present study was to develop and evaluate the psychometric properties of the TDIS to determine whether it is fit-for-purpose to measure TD impact. METHODS: Data from qualitative studies and phase 3 trials of a VMAT2 inhibitor for the treatment of TD (KINECT3 and KINECT4) were used to determine the psychometric properties of the TDIS. Qualitative research included concept elicitation and cognitive debriefing interviews with TD patients and their caregivers in order to assess how well the TDIS captured key domains of TD impact. Quantitative analyses to examine the psychometric properties of the TDIS included assessing construct validity (factor structure, known groups, and predictive validity) and responsiveness to change. RESULTS: Qualitative results showed that the TDIS captures the key TD impacts reported by patients and caregivers and that the TDIS was interpreted as intended and relevant to patients' experiences. Quantitative results found evidence of 2 underlying domains of the TDIS: physical and socioemotional (Comparative Fit Index > 0.9). Known groups and predictive validity indicated that, compared with the AIMS, the TDIS captures unique content (correlation between AIMS and TDIS = 0.2-0.28). The TDIS showed responsiveness to change in treatment, with TDIS scores improving over 48 weeks in the 2 phase 3 trials. CONCLUSIONS: The TDIS captures relevant information about the impact of TD and is easily administered in a clinician's office or patient's home. It may be used longitudinally to show changes in TD burden over time. The TDIS complements the AIMS; using these assessments together provides a more holistic assessment of TD.

Tardive dyskinesia is a condition where people have uncontrollable movements because of taking certain medications for a long time. It is still poorly understood how these uncontrollable movements affect a person's everyday activities. We created a questionnaire called the Tardive Dyskinesia Impact Scale (TDIS). The TDIS is a questionnaire where people with tardive dyskinesia rate how their symptoms affect daily activities such as speaking and walking. People can also rate how the uncontrollable movements make them feel. We used specific tests called psychometric tests to see if the TDIS measures the correct information and if the information is reliable. Findings from this study show that the TDIS is a good way to measure how a person's uncontrollable movements affect everyday activities. The results also show that when people take medicine to help with their symptoms, their TDIS scores are better. When patients stopped taking the medicine, their symptoms were worse, and their TDIS score was worse. The TDIS can help people explain how their uncontrollable movements affect their daily life. This can then help their doctors understand the person's condition better.

Investigating Real-World Benztropine Usage Patterns in Movement Disorders: Claims Analysis and Health Care Provider Survey Results.

Objective: To evaluate real-world treatment patterns for patients initiating benztropine and to understand treatment approaches in patients with drug-induced movement disorders from a health care provider perspective.Methods: A retrospective claims analysis was conducted among patients with evidence of benztropine initiation from January 2017 through March 2020 to assess treatment patterns and patient health care resource utilization. Subsequently, a 30-minute, United States-based online survey fielded from December 2021 to January 2022 was sent to physicians, nurse practitioners, and physician assistants who reported a primary care or psychiatry specialty currently treating drug-induced movement disorders and prescribed benztropine.Results: The health care claims analysis included 112,542 patients. Polypharmacy and multiple comorbidities were frequent characteristics in this population; 54.1% of patients had ≥ 2 comorbidities at baseline, and 59.1% had claims for > 10 medications. Benztropine was used for > 3 months in > 50% of the population. Health care costs and resource utilization were high, with mean all-cause pharmacy and outpatient costs totaling $11,755. Survey results from 349 primary care or psychiatry health care providers indicated that benztropine is often used in non-tardive dyskinesia drug-induced movement disorders but frequently continued for > 3 months or used in tardive dyskinesia. In this study, psychiatry providers prescribed benztropine in line with guideline recommendations more often than primary care providers; however, < 40% indicated familiarity with 2020 American Psychiatric Association Practice Guideline for the Treatment of Patients with Schizophrenia.Conclusions: These complementary analyses suggest that benztropine is used long-term in non-tardive dyskinesia drug-induced movement disorders and in tardive dyskinesia despite risks of worsening tardive dyskinesia or adverse effects.Prim Care Companion CNS Disord 2023;25(4):22m03472. Author affiliations are listed at the end of this article.

Exploring real-world symptom impact and improvement in well-being domains for tardive dyskinesia in VMAT2 inhibitor-treated patients via clinician survey and chart review.

Introduction: Two vesicular monoamine transporter 2 (VMAT2) inhibitors are approved in the United States (US) for the treatment of tardive dyskinesia (TD). There is a paucity of information on the impact of VMAT2 inhibitor treatment on patient social and physical well-being. The study objective was to elucidate clinician-reported improvement in symptoms and any noticeable changes in social or physical well-being in patients receiving VMAT2 inhibitors. Methods: A web-based survey was offered to physicians, nurse practitioners, and physician assistants based in the US who prescribed valbenazine for TD within the past 24 months. Clinicians reported data from the charts of patients who met the inclusion criteria and were allowed to recall missing information. Results: Respondents included 163 clinicians who reviewed charts of 601 VMAT2-treated patients with TD: 47% had TD symptoms in ≥2 body regions, with the most common being in the head or face and upper extremities. Prior to treatment, 93% of patients showed impairment in ≥1 social domain, and 88% were impaired in ≥1 physical domain. Following treatment, among those with improvement in TD symptoms (n = 540), 80% to 95% showed improvement in social domains, 90% to 95% showed improvement in physical domains, and 73% showed improvement in their primary psychiatric condition. Discussion: In VMAT2-treated patients with TD symptom improvement, clinicians reported concomitant improvement in psychiatric disorder symptoms and in social and physical well-being. Regular assessment of TD impact on these types of domains should occur simultaneously with movement disorder ratings when evaluating the value of VMAT2 inhibitor therapy.

Clinician Perceptions of the Negative Impact of Telehealth Services in the Management of Drug-Induced Movement Disorders and Opportunities for Quality Improvement: A 2021 Internet-Based Survey.

Purpose: 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.

Clinically relevant effects of solriamfetol on excessive daytime sleepiness: a posthoc analysis of the magnitude of change in clinical trials in adults with narcolepsy or obstructive sleep apnea.

STUDY OBJECTIVES: To evaluate the clinical relevance of solriamfetol in treating excessive daytime sleepiness in participants with narcolepsy or obstructive sleep apnea (OSA). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. CLINICAL TRIAL REGISTRATIONS: 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.

Obstructive sleep apnea and risk of motor vehicle accident.

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.

Indirect treatment comparison of solriamfetol, modafinil, and armodafinil for excessive daytime sleepiness in obstructive sleep apnea.

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.

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.

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.

Prevalence of sleepiness and associations with quality of life in patients with sleep apnea in an online cohort.

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.

Prevalence of narcolepsy and other sleep disorders and frequency of diagnostic tests from 2013-2016 in insured patients actively seeking care.

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.

Effects of Solriamfetol on Quality-of-Life Measures from a 12-Week Phase 3 Randomized Controlled Trial.

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).

Comparison of first refill rates among users of sertraline, paroxetine, and citalopram.

BACKGROUND: Research suggests high rates of discontinuation of selective serotonin reuptake inhibitors (SSRIs). OBJECTIVE: 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. METHODS: 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 copayment >15 dollars. RESULTS: 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, P<0.001). In the logistic regression, the effects of age, sex, and copayment were not significant. CONCLUSIONS: 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.

Improving adherence to sertraline treatment: the effectiveness of a patient education intervention.

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.

The impact of urinary incontinence on quality of life of the elderly.

OBJECTIVES: To investigate the impact of urinary incontinence (UI) on health-related quality of life (QOL), as measured by the Medical Outcomes Study Short Form-36 (SF-36) and to compare UI and non-UI elderly Medicare beneficiaries enrolled in managed care plans on the prevalence of depression and self-rated health. METHODS: After excluding beneficiaries younger than 65 years old, a total of 141 815 completed surveys were used for analysis. The survey included 1 question on difficulty in controlling urination, 3 questions on depression, 3 questions on health, a series of questions regarding comorbid medical conditions, and the SF-36. Self-rated health, prevalence of depression, and scores in each domain of QOL were compared between UI and non-UI groups. RESULTS: Overall, the prevalence of UI was 24.7% (20.9% in men, 27.5% in women). The UI group was about twice as likely to feel depressed as the non-UI group. The UI group also rated their health more negatively. Compared with continent respondents, those who were incontinent had lower standardized scores on all 8 subscales of SF-36 as well as 2 summary scores. Results from multiple regressions indicated that UI had a significantly negative impact on all aspects of QOL after adjusting for comorbidities and demographic differences. CONCLUSION: Findings indicate that elderly patients with UI are more depressed and have worse perceived health. On certain domains of QOL, the negative impact of UI even surpasses that of other severe comorbidities.

A Post Hoc Analysis of HbA1c, Hypoglycemia, and Weight Change Outcomes with Alogliptin vs Glipizide in Older Patients with Type 2 Diabetes.

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 < 0.03). Patients with a baseline HbA1c of <8.0% receiving alogliptin were also more likely to achieve HbA1c ≤7.0% without hypoglycemia or weight gain than those receiving glipizide (29% vs 13%, p < 0.03). CONCLUSION: Alogliptin demonstrated similar efficacy to glipizide in lowering HbA1c in older patients with T2DM, but with significantly more patients achieving an HbA1c ≤7.0% without hypoglycemia or an increase in body weight. These results particularly apply to patients with baseline HbA1c below 8.0%. FUNDING: The study was sponsored by Takeda Global Research & Development Center, Inc., Deerfield, IL, and Takeda Global Research and Development Centre Ltd., London, United Kingdom.

A comparison of all-cause mortality with pioglitazone and insulin in type 2 diabetes: an expanded analysis from a retrospective cohort study.

OBJECTIVES: The objectives of this study were to assess and compare all-cause mortality rates between pioglitazone (PIO) and insulin (INS). RESEARCH DESIGN: 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. MAIN OUTCOME MEASURES: 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. RESULTS: After adjustment for >40 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. CONCLUSION: PIO was associated with a lower risk of all-cause mortality than INS.

Management of patients using combination therapy with pioglitazone and a dipeptidyl peptidase-4 inhibitor: an analysis of initial versus sequential combination therapy.

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.