Health care resource use and cost differences by opioid therapy type among chronic noncancer pain patients.

The study assessed 12-month chronic pain (CP)-related health care utilization and costs among chronic noncancer pain (CNCP) patients who initiated various long-term opioid treatments. Treatments included monotherapy with long-acting opioids (mono-LAOs), mono-therapy with short-acting opioids (mono-SAOs), both LAOs and SAOs (combination), and opioid therapy initiated with SAO or LAO and switched to the other class (switch). Using MarketScan® claims databases (2006-2012), we identified CNCP patients with ≥90 days opioid supply after pain diagnosis and continuous enrollment 12 months before pain diagnosis (baseline period) and 12 months after opioid start (post-index period). Outcomes included CP-related health care utilization and costs. Among CNCP patients (n=21,203), the cohort distribution was 74% mono-SAOs, 22% combination, 2% mono-LAOs, and 2% switch. During follow-up, the average daily morphine equivalent dose was highest in mono-LAO patients (96.4 mg) compared with combination patients (89.8 mg), switch patients (64.3 mg), and mono-SAO patients (36.2 mg). After adjusting for baseline differences, the mono-LAO cohort had lower total CP-related costs ($4,933) compared with the mono-SAO ($8,604), switch ($10,470), and combination ($15,190) cohorts (all: P<0.05). Mono-LAO patients had greater CP-related prescription costs but lower medical costs than the other cohorts during the follow-up period, including lower CP-related hospitalizations (1% vs 11%-20%), emergency department visits (4% vs 11%-18%), and diagnostic radiology use (21% vs 54%-61%) (all: P<0.001). Use of pain-related medications and other treatment modalities was also significantly lower in the mono-LAO cohort relative to the other cohorts. CNCP patients using long-term monotherapy with LAOs had the lowest CP-related total health care costs in the 12 months after opioid initiation compared with mono-SAO, switch, or combination patients despite higher opioid daily doses and higher prescription costs. Future research accounting for severity and duration of pain would aid in determining the optimal long-term opioid regimen for CNCP patients.

Burden of Alcohol Abuse or Dependence Among Long-Term Opioid Users with Chronic Noncancer Pain.

BACKGROUND: Substance abuse disorders among chronic noncancer pain (CNCP) patients add to the clinical challenges and economic burden of caring for such patients. Despite potential risks, some CNCP patients with a history of alcohol abuse or dependence (AAD) and pain that is refractory to nonopioid treatment options may still need opioids for pain management. However, there is a lack of data on adverse outcomes in long-term opioid users with CNCP and a history of substance abuse or AAD disorders. OBJECTIVE: To compare adverse outcomes and all-cause health care costs among CNCP patients on long-term opioid treatment with and without a previous diagnosis of AAD. METHODS: Using MarketScan claims databases (2006-2012), CNCP patients with ≥ 90 days of opioid supply after CNCP diagnosis and continuous enrollment 12 months before CNCP diagnosis (baseline period) and 12 months after opioid start (post-index period) were identified. AAD was defined by diagnosis codes at any time before opioid initiation. Outcomes included opioid overdose, accident, and injury episodes identified by ICD-9-CM diagnoses codes. T-tests and Mann-Whitney tests compared continuous measures, and chi-square and Fisher's exact tests compared categorical measures between those with and without AAD. Multivariable analyses for outcomes were conducted, adjusting for baseline differences between cohorts. RESULTS: Of 21,203 CNCP patients with long-term opioid treatment, 750 (3.5%) had an AAD diagnosis before opioid initiation. AAD patients were significantly younger (48.4 [SD ± 11.4] years vs. 52.8 [SD ± 14.8] years), less likely to be enrolled in Medicare (17% commercial vs. 4% Medicare), and more likely to be male (67% vs. 48%; all P < 0.001). There were no differences in type or number of CNCP diagnoses or Charlson Comorbidity Index (CCI) scores. Patients with AAD had significantly higher rates of depression and anxiety diagnoses, antidepressant and benzodiazepine use, and drug abuse/dependence diagnoses in the baseline period. Twelvemonth post-index rates of opioid overdose (1.2% vs. 0.2%), accident (7.3% vs. 2.8%), and injury (46.1% vs. 36.8%) were greater in the AAD cohort (all P < 0.001). The differences were nonsignificant for accidents in multivariable analyses. While mean prescription costs were similar ($3,562 vs. $3,312; P = 0.212), AAD patients had significantly higher mean all-cause medical costs ($28,429 vs. $22,082; P < 0.001) and significantly higher all-cause total health care costs ($31,991 vs. $25,395; P < 0.001). The cost differences remained significant in multivariable analyses. CONCLUSIONS: In the first year after long-term opioid initiation, CNCP patients with a previous AAD diagnosis had 5 times the rate of opioid overdose, 2.3 times the rate of accidents, 1.2 times the rate of injury, and higher all-cause health care costs compared with those not diagnosed with AAD. DISCLOSURES: Funding for this research study and resultant publication was provided by Teva Global Health Economics and Outcomes Research, which fully reviewed the manuscript. Gajria and Yeung are employees of Teva Pharmaceuticals. White was an employee of Teva Pharmaceuticals at the time this research was conducted. Blumberg and Coutinho are employees of Xcenda, which received research funding from Teva Pharmaceuticals for the conduct of this study and for the preparation of this manuscript. Katz has received research funding and consulting fees from Teva Pharmaceuticals unrelated to this study. Study concept and design were contributed by Katz, White, and Blumberg, along with Coutinho and Yeung. Coutinho took the lead in data collection, assisted by the other authors. Data interpretation was performed by Blumberg, Katz, and Gajria, along with the other authors. The manuscript was written by Gajria, Yeung, Coutinho, and Blumberg, along with Katz and White, and revised by Gajria, Blumberg, Katz, and Coutinho, along with Yeung and White.

Humanistic and economic burden of nausea and vomiting among migraine sufferers.

BACKGROUND: While studies have demonstrated the economic burden of migraines in terms of quality of life, health care resource use (HRU), and costs, there exists a notable paucity of data comparing such outcomes among migraineurs with nausea and vomiting (N/V) and those without. The current study aimed to address this gap. METHODS: This was a retrospective study using data from the 2013 US National Health and Wellness Survey, a cross-sectional, internet-based survey. Respondents self-reported their migraine with or without N/V along with demographics and outcomes including depression (Patient Health Questionnaire total score; PHQ-9), sleep problems (11-item total score of sleep problems), HRU (number of physician visits, emergency room [ER] visits, and hospitalizations) and Work Productivity and Activity Impairment-General Health Scale (WPAI-GH), and associated mean annual costs. Generalized linear models, adjusting for covariates, assessed the burden of N/V on all outcomes. RESULTS: Among all migraineurs (N=7,855), 73.4% were female, mean age was 41.82 years old, and 57.6% reported experiencing N/V. Adjusting for covariates, migraineurs with N/V vs without N/V had higher mean PHQ-9 scores (7.91 vs 7.02, p<0.001) and mean sleep problems (3.29 vs 2.64, p<0.001). Mean ER visits were more frequent among migraineurs with N/V than those without N/V (0.48 vs 0.38, p=0.001). This difference translated into a 26.3% increase in estimated mean ER costs (N/V=US$1,499 vs without N/V=US$1,187, p=0.002). Mean percentage activity impairment was higher in migraineurs with N/V than in those without N/V (37.73% vs 35.12%, p=0.002) and migraineurs with N/V had higher work productivity loss costs (N/V=US$10,344 vs without N/V=US$9,218, p=0.016). CONCLUSION: Migraine patients with N/V reported worse depression, sleep problems, and activity impairment, and higher ER visits than those without N/V. Migraine with N/V was also associated with an increase in mean annual ER visit costs and work productivity loss costs. Study findings suggest unmet needs with current treatment options for migraine patients with N/V.

The impact of adjunctive guanfacine extended release on stimulant adherence in children/adolescents with attention-deficit/hyperactivity disorder.

AIM: To assess stimulant adherence among children/adolescents with attention-deficit/hyperactivity disorder (ADHD) augmenting stimulants with guanfacine extended-release (GXR). PATIENTS & METHODS: Inclusion criteria: 6-17 years, ≥1 ADHD diagnosis, ≥1 long-acting and/or short-acting stimulant with GXR augmentation. Modified medication possession ratio (mMPR; days medication available/days in period, excluding medication holidays) was assessed; mMPR <0.80 nonadherent. Regression models assessed change in mMPR adjusting for demographic and clinical characteristics. RESULTS: Among patients nonadherent to stimulants pre-augmentation (n = 165), unadjusted mean (SD) pre- and post-stimulant mMPRs were 0.68 (0.11) and 0.87 (0.16). Adjusted mean change in mMPR was 0.20 for long-acting versus 0.18 for short-acting stimulants (p = 0.34). CONCLUSION: Among patients nonadherent to stimulants, GXR augmentation was associated with increased stimulant adherence.

Impact of breakthrough pain on community-dwelling cancer patients: results from the National Breakthrough Pain Study.

OBJECTIVE: To characterize cancer-related breakthrough pain (BTcP) among community-dwelling patients with cancer. METHODS: Data from the National Breakthrough Pain Study, a cross-sectional observational survey describing breakthrough pain (BTP) in the community, were analyzed for a subset of patients with BTcP. Eligible patients were community-dwelling adults with commercial insurance and insurance claims consistent with cancer and chronic pain who consented to a structured telephone interview. Assessments included the Brief Pain Inventory-Short Form (BPI), the Short Form 12 Health Survey, the Sheehan Disability Scale, the Work Performance Questionnaire, Generalized Anxiety Disorder-7 Screener, and Patient Health Questionnaire-2. RESULTS: In total, 112 patients with cancer pain also experienced BTcP; 83.3% were in remission. Most patients reported experiencing ≥2 BTcP episodes per day, a median time to BTcP peak of 15 minutes, and a median duration of BTcP of 30 minutes. Mild pain at onset that gradually worsened was reported by 54.5% of patients, and incidental pain triggered by physical activity was reported by 58.0%. Most patients who reported using a medication to manage BTcP received an oral immediate-release opioid, such as oxycodone or hydrocodone, and only 1 received a rapid-onset opioid; few (24.1%) reported that pharmacologic treatment for BTcP worked every time. Patients reported mean (standard deviation) BPI scores of 4.2 (1.75) and 5.7 (1.98) for average and worst pain intensity during the preceding 24 hours, respectively, and high interference with activity, mood, ability to walk and work, social relations, sleep, and enjoyment of life. CONCLUSION: Results indicate that BTcP among community-dwelling patients with cancer continues to be a health burden and reveals opportunities to improve its management.

The Caregiver Perspective on Paediatric ADHD (CAPPA) survey: Understanding sociodemographic and clinical characteristics, treatment use and impact of ADHD in Europe.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects the lives of patients and their families. The Caregiver Perspective on Paediatric ADHD (CAPPA) survey was conducted to evaluate the burden associated with ADHD in Europe and to identify unmet needs. Here, we describe sociodemographic and clinical characteristics, treatment use and impact of ADHD. METHODS: The cross-sectional web-based CAPPA survey was fielded in 10 European countries among caregivers of children/adolescents (aged 6-17 years) with ADHD who were currently receiving or had received pharmacotherapy in the previous 6 months. RESULTS: Data on 3688 completed CAPPA surveys were evaluated. Children/adolescents were diagnosed with ADHD at a mean age of 6.9 years; 80% were male. Most children/adolescents (56%) had undergone behavioural therapy. Overall, 78% of children/adolescents currently received ADHD pharmacotherapy; high rates of atypical antipsychotic use were reported in some countries. Overall, 23% of children/adolescents had repeated a school year and 4% had been expelled recently. Most caregivers (68-88%) reported difficulty with schoolwork, social interactions/activities and family relationships, even when the child/adolescent was receiving ADHD medication. Almost one third (31%) of caregivers felt the need to change employment status despite their child/adolescent receiving ADHD medication in 53% of these cases. LIMITATIONS: Information was reported by caregivers recruited through market research panels; reporting, recall and selection biases may be present. CONCLUSION: Variation across Europe was observed in characteristics of caregivers and children/adolescents with ADHD, and treatment use. Even with medication, ADHD compromised or negatively impacted caregivers' work and children/adolescents' schoolwork, their social interactions and family relationships.

Psychometric validation of the Weiss Functional Impairment Rating Scale-Parent Report Form in children and adolescents with attention-deficit/hyperactivity disorder.

BACKGROUND: Measurement properties of the Weiss Functional Impairment Rating Scale-Parent Report Form (WFIRS-P), which assesses attention-deficit/hyperactivity disorder (ADHD)-related functional impairment in children/adolescents (6-17 years), were examined. METHODS: Data from seven randomized, controlled trials were pooled. Analyses were conducted in two random half-samples. WFIRS-P conceptual framework was evaluated using confirmatory factor analyses (CFA). Reliability was estimated using internal consistency (Cronbach's alpha) and test-retest reliability methods. Convergent validity was assessed using correlations between WFIRS-P domain scores and the ADHD-RS-IV and Clinical Global Impression-Severity (CGI-S) scales. Responsiveness was tested by comparing mean changes in WFIRS-P domain scores between responders and non-responders based on clinical criteria. RESULTS: CFA adequately confirmed the item-to-scale relationships defined in the WFIRS-P conceptual framework. Cronbach's alpha coefficient exceeded 0.7 for all domains and test-retest reliability exceeded 0.7 for all but Risky Activities. With few exceptions, WFIRS-P domains correlated significantly (p < 0.05) with ADHD-RS-IV Total, Inattention and Hyperactivity-Impulsivity scores and CGI-S at baseline and follow-up in both random half-samples. Mean changes in WFIRS-P domain scores differed significantly between responder and non-responder groups in the expected direction (p < 0.001). CONCLUSIONS: Study results support the reliability, validity and responsiveness of the WFIRS-P. Findings were replicated between two random samples, further demonstrating the robustness of results.

Preferences for Attention-Deficit/Hyperactivity Disorder (ADHD) Non-Stimulant Treatment Characteristics Among Children and Adolescents With ADHD and Their Caregivers.

Background: Understanding patient and caregiver preferences for treatment is important for optimizing treatment decisions. Non-stimulant therapies are an alternative treatment option to stimulant therapy for attention-deficit/hyperactivity disorder (ADHD). Guanfacine extended release (GXR) and atomoxetine (ATX) are two non-stimulant medications approved in the United States for the treatment of ADHD. Objective: To identify non-stimulant ADHD medication attributes important to caregivers/patients. Methods: US caregivers of ADHD patients (6-17 years) and child/adolescent patients (10-17 years) completed an adaptive conjoint analysis survey. Respondents selected between hypothetical treatments with different attributes. Ordinary least-squares and hierarchical Bayes regression using Sawtooth Software were used to calculate utilities, importance ratings, and preferences. Results: 483 caregivers (mean age: 41.9 years, standard deviation [SD]: 8.7; 75% female) and 211 children/adolescents (mean age: 14.5 years, SD: 2.2; 70% male) completed the survey. Based on importance ratings, the most influential attributes for both caregivers and children/adolescents were chance of somnolence, efficacy, and for caregivers, effect on oppositionality and black box warning. Most caregivers (95.3%) and children/adolescents (93.8%) preferred GXR over ATX. In several sensitivity analyses in which attribute levels varied, GXR remained the preferred medication with the exception of one scenario. Conclusions: Children/adolescents and caregivers demonstrated in this study that they can clearly express their preferences for treatment attributes and treatment choices; in this case they preferred GXR to ATX. Patients and caregiver preferences could be useful inputs to the treatment selection decision-making process.

Adherence, persistence, and medication discontinuation in patients with attention-deficit/hyperactivity disorder - a systematic literature review.

Untreated attention-deficit/hyperactivity disorder (ADHD) can lead to substantial adverse social, economic, and emotional outcomes for patients. The effectiveness of current pharmacologic treatments is often reduced, due to low treatment adherence and medication discontinuation. This current systematic literature review analyzes the current state of knowledge surrounding ADHD medication discontinuation, focusing on: 1) the extent of patient persistence; 2) adherence; and 3) the underlying reasons for patients' treatment discontinuation and how discontinuation rates and reasons vary across patient subgroups. We selected 91 original studies (67 with persistence/discontinuation results, 26 with adherence results, and 41 with reasons for discontinuation, switching, or nonadherence) and 36 expert opinion reviews on ADHD medication discontinuation, published from 1990 to 2013. Treatment persistence on stimulants, measured by treatment duration during the 12-month follow-up periods, averaged 136 days for children and adolescents and 230 days for adults. Owing to substantial study heterogeneity, comparisons across age or medication type subgroups were generally inconclusive; however, long-acting formulations and amphetamines were associated with longer treatment duration than short-acting formulations and methylphenidates. The medication possession ratio, used to measure adherence, was <0.7 for all age groups and medication classes during a 12-month period. Adverse effects were the most commonly cited reason for discontinuation in all studies. Original research studies reported the lack of symptom control as a common discontinuation reason, followed by dosing inconvenience, social stigma associated with ADHD medication, and the patient's attitude. In summary, although there was a lack of consistency in the measurement of adherence and persistence, these findings indicate that drug adherence and persistence are generally poor among patients with ADHD. Clinicians may be able to help improve adherence and persistence to ADHD treatment by educating caregivers and patients on treatment goals, administering long-acting medications, and following-up with patients to verify if medication is still effective and well-tolerated.

Impaired health status and the effect of pain and fatigue on functioning in clinical trial patients with systemic lupus erythematosus.

OBJECTIVE: Our study evaluated the impaired health status of clinical trial patients with systemic lupus erythematosus (SLE) and explored the relationship between changes in fatigue and pain and their effect on overall health status. METHODS: Pooled treatment and placebo data from a phase Ib clinical trial of adults with moderate/severe SLE were analyzed. Measures included patient-reported Medical Outcome Study Short Form-36 Survey, Version 2 (SF-36v2), Fatigue Severity Scale, and numeric rating scales (NRS) for pain and global health assessment and clinician-reported global assessment of disease activity (MDGA). Disease burden was compared to the US general population. Health status of responders and nonresponders on pain or fatigue were compared. RESULTS: The sample included 161 patients with SLE, predominantly female (96%) and white (72%), with average age of 43 ± 11 years. Mean SF-36v2 component summary scores reflected overall problems with physical [physical component summary (PCS); 35.2 ± 9.7] and mental health (mental component summary; 40.9 ± 12.9). Patients with SLE had worse health status on all SF-36v2 subscales than the US general population and comparable age and sex norms (effect size -0.51 to -2.15). Pain and fatigue responders had greater improvements on SF-36v2 scores (bodily pain, physical functioning, social functioning, PCS), patient global health assessment NRS, and MDGA than nonresponders. There was moderate agreement in responder status, based on global assessments by patients and clinicians (68.1%), with some discrepancy between patients who were MDGA responders but patient assessment nonresponders (27.7%). CONCLUSION: Improvements in patient-reported pain or fatigue correlated with improvements in overall health. Patient assessments offer a unique perspective on treatment outcomes. Patient-reported outcomes add value in understanding clinical trial treatment benefits.

Medical costs and healthcare resource use in patients with lupus nephritis and neuropsychiatric lupus in an insured population.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect multiple organ systems, including the kidneys (lupus nephritis) and the central nervous system (neuropsychiatric lupus, or NPSLE). The healthcare costs and resource utilization associated with treating lupus nephritis and NPSLE in a large US managed care plan were studied. METHODS: SLE subjects ≥18 years of age and with claims-based evidence of nephritis or neuropsychiatric conditions were identified from a health plan database. An index date was set as a randomly drawn date from all qualifying claims during 2003-2008 for study subjects. Subjects were matched on the basis of demographic and clinical characteristics to unaffected controls. Costs and resource use were determined during a fixed 12-month post-index period. RESULTS: Nine hundred and seven lupus nephritis subjects were matched to controls, and 1062 subjects with NPSLE were matched to controls. Mean overall post-index healthcare costs were significantly higher among subjects with lupus nephritis in comparison to matched controls ($33,472 vs $5347, p < 0.001). Similarly, mean overall post-index healthcare costs were significantly higher among subjects with NPSLE compared to controls ($30,341 vs $4646, p < 0.001). Subjects with lupus nephritis or NPSLE had higher mean post-index numbers of ambulatory visits, specialist visits, emergency department visits and inpatient hospital stays, compared to controls (all p < 0.001). LIMITATIONS: Additional research, such as medical chart review, could provide validation for the claims-based identification of lupus nephritis and NPSLE subjects. Also, indirect costs were not evaluated in this study. CONCLUSION: Subjects with lupus nephritis or NPSLE have high costs and resource use, compared to unaffected controls.

Epidemiology of adult idiopathic inflammatory myopathies in a U.S. managed care plan.

INTRODUCTION: Idiopathic inflammatory myopathies have a reported incidence of 0.1 to 1 per 100,000 person-years and prevalence of 0.55 to 6 per 100,000 in the United States. METHODS: We retrospectively examined medical claims for adults aged ≥18 years with myositis (International Classification of Diseases, Ninth Revision, Clinical Modification codes 710.3 [dermatomyositis], 710.4 [polymyositis], and 728.81 [interstitial myositis]) from 2003 to 2008 in a large US managed care database. RESULTS: The incidence and prevalence cohorts comprised 1,941 and 3,112 subjects, respectively. From 2003 to 2008, the adjusted annual incidence of myositis ranged from 5.8 to 7.9 per 100,000 person-years, and the annual prevalence of myositis ranged from 14.0 to 17.4 per 100,000. CONCLUSIONS: The incidence and prevalence of idiopathic inflammatory myopathies in the managed care plan studied was higher than previously reported in the United States. Because of the limitations inherent in claims analysis, additional research is needed to substantiate these results.

Functionality and health-status benefits associated with reduction of osteoarthritis pain.

OBJECTIVE: To evaluate the association between pain intensity improvement and improvements in functionality and health status in patients with chronic osteoarthritis pain of the hip or knee. METHODS: Data were obtained from a 12-week, randomized, double-blind, placebo-controlled study of tramadol ER 100 mg, 200 mg, 300 mg, or 400 mg once daily. Patients reported pain intensity with a 100-mm visual analog scale (0 = no pain, 100 = extreme pain) and functionality and health status with the disease-specific Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire and the generic Short-Form-36 Health Survey (SF-36). Pain intensity improvement from baseline was categorized as < 0%, 0-14%, 15-29%, 30-49%, 50-69%, and >or= 70%, and mean changes in WOMAC and SF-36 scores were determined for patients in each category. RESULTS: A total of 1011 patients received placebo (n = 205) or tramadol ER 100 mg (n = 202), 200 mg (n = 201), 300 mg (n = 201), or 400 mg (n = 202). The degree of pain intensity improvement was correlated with the degree of improvement in WOMAC and SF-36 scores; as little as 15% reduction of pain intensity was associated with notable improvements in function and health status. Potential limitations included the lack of established thresholds to assess clinically meaningful changes in these outcomes. CONCLUSIONS: Pain intensity improvement is associated with corresponding improvements in function and health status. While large improvements in pain intensity are associated with large improvements in health status and functionality, modest pain reductions are also associated with improvement of certain health status parameters.

Development and validation of the Premenstrual Symptoms Impact Survey (PMSIS): a disease-specific quality of life assessment tool.

OBJECTIVE: To develop and validate the Premenstrual Symptoms Impact Survey (PMSIS), a brief web-based instrument for evaluating the impact of premenstrual symptoms on health-related quality of life (HRQOL). METHODS: An item bank of 68 questions was administered to a nationally representative sample of 971 women using the web, aged 18-45, who experienced regular menstrual cycles in the past 3 months, were not currently pregnant or breastfeeding, and were not being treated or taking medications for depression-related disorders in the last 2 years. Item reduction was performed using forward stepwise linear regression of an overall symptom severity score onto item scores. Three standards were used to validate the instrument: (1) the American College of Obstetricians and Gynecologists retrospective diagnostic criteria for identifying participants "at risk" for clinically significant premenstrual syndrome (PMS), (2) the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders retrospective diagnostic criteria for identifying participants at risk for premenstrual dysphoric disorder (PMDD), and (3) the Medical Outcomes Study Short Form (SF-12) Health Survey. RESULTS: Six items met entry criteria in the model. Approximately 6.0% of the participants were identified as being at risk for PMDD, and 17.3% were identified as being at risk for clinically significant PMS. PMSIS scale score differed significantly between participants who were and were not at risk for PMDD/clinically significant PMS. PMSIS scale score also differed significantly between participants having either high, average, or low HRQOL as defined by SF-12 physical and mental component summary scores. CONCLUSIONS: These results demonstrate that the PMSIS has excellent discriminative ability to detect differences in groups that are known to differ in terms of clinical criteria. The PMSIS can be used to educate consumers about the impact of their symptoms on QOL.

Health-Related Quality-of-Life Outcomes in Patients Treated with Push-Pull OROS Hydromorphone versus Extended-Release Oxycodone for Chronic Hip or Knee Osteoarthritis Pain: A Randomized, Open-Label, Parallel-Group, Multicenter Study.

BACKGROUND: Chronic osteoarthritis (OA) pain impacts health-related quality of life (HR-QOL). OBJECTIVE: The primary aim of this study was to evaluate and compare HR-QOL outcomes following treatment with once-daily push-pull Osmotic controlled-Release Oral delivery System (OROS) hydromorphone versus twice-daily extended-release (ER) oxycodone for moderate to severe chronic knee or hip OA pain. METHODS: This was a 6-week, randomized, open-label, parallel-group, multicenter study of 124 patients with OA whose pre-trial treatment included NSAIDs or other non-steroidal, non-opioid analgesics. The HR-QOL of patients was assessed using the Medical Outcomes Study (MOS) Sleep Scale and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC™). Within- and between-group changes from baseline to 6 weeks were evaluated using ANOVA. RESULTS: At baseline, trial patients had significantly worse MOS Sleep Scale (multivariate ANOVA [MANOVA] F = 11.0, p < 0.001) and WOMAC™ scores (MANOVA F = 55.7, p < 0.001) than chronic disease benchmarks. Both treatment groups showed significant improvements on the sleep disturbance scale (p < 0.01), with additional improvements observed with OROS hydromorphone on the sleep quantity (p = 0.046), sleep snoring (p = 0.044), awaken short of breath or with a headache (p = 0.024), 6-item sleep problems index I (p < 0.001), and 9-item sleep problems index II (p < 0.001) scales. Significant treatment differences in favor of OROS hydromorphone over ER oxycodone were also observed on the awaken short of breath or with a headache (p = 0.014) scale and sleep problems index I (p = 0.045). Both treatment groups showed comparable large effect size (>0.8 SD unit) improvements on the WOMAC™ scale (measuring functionality outcomes such as pain, stiffness, physical function etc). CONCLUSION: Both OROS hydromorphone and ER oxycodone improved sleep and function, with greater sleep benefits being observed in patients treated with OROS hydromorphone.

Mapping MOS Sleep Scale scores to SF-6D utility index.

OBJECTIVE: Deriving preference scores for the Medical Outcomes Study (MOS) Sleep Scale would enable its use in cost-utility analyses. The objective of this study was to map scores of the MOS Sleep Scale to a preference-based health-state utility index (SF-6D) scored from the SF-36 Health Survey (SF-36). RESEARCH DESIGN AND METHODS: Three datasets were used: (1) the MOS study, a 4-year observational study of chronically ill patients, (2) a 7-week open-label, non-comparative clinical trial of an osmotic controlled-release oral delivery system (OROS) hydromorphone in the treatment of chronic low back pain (CLBP), and (3) a 6-week open-label randomized controlled trial of OROS hydromorphone in the treatment of pain associated with chronic osteoarthritis (OA). Various models were tested, where SF-6D was regressed onto the Sleep Problem Index-II (SLP9) in 1000 random half (developmental) samples of the MOS (n = 1413). The best fitting model was applied to the other 1000 random half (cross-validation) samples of the MOS (n = 1412), and to the two trial samples (n = 199 in the CLBP trial; n = 124 in the OA trial). RESULTS: The best fitting model in the MOS samples included a quadratic term for the SLP9 which explained 34% of the variance in SF-6D in the developmental samples. Errors in prediction were greatest at higher SLP9 scores. Addition of demographic and clinical variables to the model explained minimal incremental amounts of variance (< 5%) in SF-6D scores. These results were replicated in the cross-validation MOS samples. In both developmental and cross-validation MOS samples, mean predicted and observed SF-6D scores were nearly identical. When the mapping algorithm developed in the MOS was applied to the CLBP sample, mean predicted SF-6D scores were 0.09 points higher than observed SF-6D scores at both baseline and final visits, while changes in predicted and observed SF-6D scores were identical. CONCLUSION: Results indicate that it is possible to map MOS SLP9 to SF-6D yielding useable preference-based scores essential for cost-utility analyses. A limitation concerns the interpretation of SF-6D scores estimated from SLP9 scores above 60, where the prediction errors increased considerably.

Pain relief and pain-related sleep disturbance with extended-release tramadol in patients with osteoarthritis.

OBJECTIVE: This analysis evaluated changes in pain and pain-related sleep disturbance with extended-release tramadol (tramadol ER) in patients with moderate, chronic osteoarthritis pain, and the influence of pain reduction on pain-related sleep disturbance. METHODS: Data were obtained from a 12-week, randomized, double-blind, placebo-controlled, fixed-dose study of tramadol ER 100 mg, 200 mg, 300 mg, or 400 mg once daily. Subjects reported osteoarthritis pain intensity with a 100-mm visual analog scale (VAS; 0 = no pain, 100 = extreme pain). A Sleep Problems Index score from 0 to 100 mm (0 = never, 100 = always) was determined from the mean of three subject-reported scores of pain-related sleep disturbance. RESULTS: A total of 815 subjects received tramadol ER (all doses combined) and 205 received placebo. Mean pain reduction at 12 weeks was -30.4 mm and -21.5 mm for tramadol ER and placebo, respectively (p < 0.001). Tramadol ER-treated subjects were nearly twice as likely as placebo subjects to have clinically meaningful pain reduction at 12 weeks, defined as 30 mm or greater reduction (odds ratio [OR] = 1.84, P < 0.001) or 30% or greater reduction (OR = 1.95, P < 0.001) in pain. Clinically meaningful reduction of pain-related sleep disturbance at 12 weeks, defined as 16 mm or greater improvement on the Sleep Problems Index, was more common for tramadol ER than placebo (51% vs. 42%, respectively, p = 0.022). Pain reduction was associated with reduced pain-related sleep disturbance (R = 0.51). Study treatment was generally well tolerated. Possible limitations included homogeneity of pain scores at baseline and the effect of adverse events on sleep analyses. CONCLUSIONS: In patients with chronic osteoarthritis pain, pain reduction is associated with decreased pain-related sleep disturbance.

A psychometric comparison of three patient-based measures of asthma control.

OBJECTIVE: Asthma is a multidimensional disease, characterized by changes in pulmonary function, transient and chronic symptoms, and effects on quality of life. In this study, we compared the psychometric properties and screening accuracy of three patient-based asthma control instruments including: the Asthma Control Test (ACT), a brief instrument developed to assess asthma control of patients in a clinical setting; the Asthma Control Questionnaire (ACQ), an instrument developed for use in clinical research; and the 'Rules of Two', a tool that has been used in both settings. METHODS: Patients (N = 313) completed the ACT, ACQ, and Rules of Two during two asthma clinic visits 4-12 weeks apart. Office staff recorded pre- and post-bronchodilator FEV(1) measurements and asthma specialists provided a global rating of asthma control. Internal consistency reliability was computed and construct validity was evaluated using analysis of variance (ANOVA). Logistic regression and receiving operating characteristic (ROC) curve analysis was conducted to compare the screening accuracy of each measure in identifying patients with uncontrolled or moderate to severe asthma. The responsiveness of each measure to changes in asthma control and severity was tested using correlational and ANOVA methods. RESULTS: Results show that the ACT and ACQ have comparable reliability, validity, screening accuracy, and responsiveness. The Rules of Two, however, did not meet some standards and therefore has weaker psychometric properties. CONCLUSION: The ACT and ACQ are comparable asthma control questionnaires. The choice of which questionnaire to use should be informed by considering several factors, such as the intended purpose and setting where the questionnaire will be used, as well as the content, practicality, availability of benchmark scores, and adaptability to multiple administration modes of each questionnaire. One potential limitation of the study is that the data were collected in a clinical setting with limited demographic information. Hence, additional studies are needed to evaluate the psychometric properties of each instrument across demographic and clinical subgroups of the general population.

Psychometric testing and validation of the Chronic Pain Sleep Inventory.

BACKGROUND: Patients with chronic pain often experience significant disruptions in sleep. A potential benefit of treatment aimed at pain relief is improved quality of sleep in patients with chronic pain. OBJECTIVE: The goal of this study was to evaluate the psychometric properties of the Chronic Pain Sleep Inventory (CPSI) and provide preliminary evidence of its construct validity in assessing sleep problems among patients with chronic pain. METHODS: Data came from four 12-week, multi-center, double-blind, randomized, placebo-controlled clinical trials of chronic low back pain and osteo-arthritis of the hip or knee. CPSI data were collected at baseline and 12 weeks. The 5 CPSI items measured trouble falling asleep (CPSI1), needing sleep medication (CPSI2), awakened by pain during the night (CPSI3) and in the morning (CPSI4), and overall quality of sleep (CPSI5) on a 100-mm visual analog scale. Exploratory and confirmatory factor analyses were conducted to evaluate the underlying dimensionality and structure of the CPSI scales. The known-groups method was used to assess validity by comparing CPSI item scores across groups of patients known to differ in the presence and severity of sleep problems as measured by the Physical Dependence Questionnaire. RESULTS: A total of 2674 patients were included in the study (mean age, 57.6 years; 61.0% female; 80.2% white). The majority of the patients were treated for chronic pain related to osteoarthritis of the hip or knee (n=2294). Findings revealed a single sleep problems index can be scored from 3 of the 5 CPSI items (CPSI1, CPSI3, and CPSI4). All 3 items attributed sleep problems to pain, with high factor loadings (>0.80) and a high internal consistency (>0.90). Moderate to high correlations (r >or= 0.50) between CPSI items demonstrated convergent validity, and weak correlations (r<0.50) with other health-related scales (the Western Ontario and McMaster Universities Osteo-arthritis Index and the 36-item Short-Form Health Survey) demonstrated discriminant validity. All CPSI items showed greater ability to discriminate and respond to changes in the presence and severity of sleep problems than the other health-related scales. CONCLUSIONS: CPSI items showed good construct validity, and the results support the scoring of a reliable single index from 3 of the 5 CPSI items that all attributed sleep problems to pain.