Cost Burden of Chronic Pain Patients in a Large Integrated Delivery System in the United States.

OBJECTIVES: To estimate all-cause healthcare resource utilization and costs among chronic pain patients within an integrated healthcare delivery system in the United States. METHODS: Electronic medical records and health claims data from the Henry Ford Health System were used to determine healthcare resource utilization and costs for patients with 24 chronic pain conditions. Patients were identified by ≥ 2 ICD-9-CM codes ≥ 30 days apart from January to December, 2010; the first ICD-9 code was the index event. Continuous coverage for 12 months pre- and postindex was required. All-cause direct medical costs were determined from billing data. RESULTS: A total of 12,165 patients were identified for the analysis. After pharmacy, the most used resource was outpatient visits, with a mean of 18.8 (SD 13.2) visits per patient for the postindex period; specialty visits accounted for 59.0% of outpatient visits. Imaging was utilized with a mean of 5.2 (SD 5.5) discrete tests per patient, and opioids were the most commonly prescribed medication (38.7%). Annual direct total costs for all conditions were $386 million ($31,692 per patient; a 40% increase from the pre-index). Pharmacy costs comprised 14.3% of total costs, and outpatient visits were the primary cost driver. CONCLUSIONS: Chronic pain conditions impose a substantial burden on the healthcare system, with musculoskeletal conditions associated with the highest overall costs. Costs appeared to be primarily related to use of outpatient services. This type of research supports integrated delivery systems as a source for assessing opportunities to improve patient outcomes and lower the costs for chronic pain patients.

Prevalence of Chronic Pain in a Large Integrated Healthcare Delivery System in the U.S.A.

BACKGROUND: There is a paucity of published data on the prevalence of chronic pain conditions within large, integrated healthcare organizations in the U.S.A. Such data are essential to inform the development of appropriate treatment programs. METHODS: Twenty-five selected pain conditions were used to identify patients receiving care within the Henry Ford Health System (HFHS) who were enrolled in the Health Alliance Plan (HAP), a subsidiary of HFHS. Patients aged ≥ 18 years, enrolled in HAP in 2010, and having ≥ 2 encounters, ≥ 30 days apart, with an ICD-9-CM diagnosis code for a pain condition of interest during 2010 were counted. Variables included in the study were as follows: age, gender, body mass index (BMI), and Charlson comorbidity conditions and index score. RESULTS: Altogether, 14,784 persons (11.6% of the total adult population) met the criteria for having a chronic pain condition. Overall, the study population was 64.4% female and had mean age (SD) of 61.2 (15.6) years and mean BMI of 31.4 (7.2) kg/m(2) . Musculoskeletal pain conditions were the most common diagnoses, comprising 75.4% of all pain diagnoses. Diabetes and chronic pulmonary disease were the most common medical comorbidities. CONCLUSIONS: In this comprehensive analysis of 2 years of data from a large, vertically integrated metropolitan health system, chronic pain was identified in 12% of adult patients. Approximately 75% of chronic pain conditions were musculoskeletal. The triad of age ≥ 60 years, BMI ≥ 30, and female sex were the most salient demographic characteristics of patients with chronic pain conditions. These diagnostic and demographic data may be used to inform treatment program development.

The Comparative Burden of Chronic Widespread Pain and Fibromyalgia in the United States.

BACKGROUND/PURPOSE: Little information exists on the comparative patient and economic burden of chronic widespread pain (CWP) and fibromyalgia (FM) in the United States. METHODS: This multistage, observational study included an online screening survey of a large geographically diverse US sample to assess CWP status, a physician/site visit to determine FM diagnosis, and an online subject questionnaire to capture clinical characteristics, pain, health status, functioning, sleep, healthcare resource use (HRU), productivity, and costs. Based on the screener and physician evaluation, mutually exclusive groups of subjects without CWP (CWP-), with CWP but without FM (CWP+), and with confirmed FM were identified. RESULTS: Disease burden was examined in 472 subjects (125 CWP-, 176 CWP+, 171 FM). Age, race, and ethnicity were similar across groups. Mean body mass index and number of comorbidities increased from CWP- to CWP+ to FM (P = 0.0044, P < 0.0001, respectively). From CWP- to CWP+ to FM, there were reductions in health status (EQ-5D, SF-12) and sleep outcomes (MOS-SS, SSQ) (all P < 0.05). Pain severity, interference with function (BPI-SF), and overall work impairment (WPAI:SHP) increased from CWP- to CWP+ to FM (all P < 0.0001). Higher proportions of CWP+ (52.8%) and FM subjects (62.6%) were taking pain-related prescription medications relative to CWP- subjects (32.8%; P < 0.0001). Significant differences in total direct and indirect costs across the three groups (both P < 0.0001) were observed, with highest costs among FM subjects. CONCLUSION: Fibromyalgia subjects were characterized by the greatest disease burden with more comorbidities and pain-related medications, poorer health status, function, sleep, lower productivity, and higher costs.

Societal and individual burden of illness among fibromyalgia patients in France: association between disease severity and OMERACT core domains.

BACKGROUND: Patients with fibromyalgia (FM) report widespread pain, fatigue, and other functional limitations. This study aimed to provide an assessment of the burden of illness associated with FM in France and its association with disease severity and core domains as defined by Outcome Measures in Rheumatology Clinical Trials (OMERACT) for FM. METHODS: This cross-sectional, observational study recruited patients with a prior diagnosis of FM from 18 community-based physician offices in France. Patients completed questions about FM impact (Fibromyalgia-Impact Questionnaire [FIQ]), core symptoms (defined by OMERACT), health-related quality of life (EQ-5D), current overall health status (rated on a scale from 0 to 100), productivity, treatment satisfaction, and out-of-pocket expenses related to FM. Site staff recorded patients' treatment and health resource use based on medical record review. Costs were extrapolated from 4-week patient-reported data and 3-month clinical case report form data and calculated in 2008 Euros using a societal perspective. Tests of significance used the Kruskal-Wallis test or Fisher's Exact test where P < 0.05 was considered significant. RESULTS: Eighty-eight patients (mean 55.2 y; female:male 74:14) were recruited. The majority of patients (84.1%) were prescribed medications for FM. Patients mainly described medications as a little/not at all effective (40.0%) or somewhat effective (52.9%). Current Overall Health rating was 52.9 (± 17.8) and FIQ total score was 54.8 (± 17.3). FIQ total score was used to define FM severity, and 17 patients scored 0- < 39 (mild FM), 33 patients 39- < 59 (moderate FM), and 38 scored 59-100 (severe FM). As FM severity level worsened, patients had poorer overall health status and perceived their prescription medications to be less effective. Average cost/FM patient was higher for severe (€10,087) vs. moderate (€6,633) or mild FM (€5,473); however, the difference was not significant. CONCLUSIONS: In a sample of 88 patients with FM from France, we found that FM poses a substantial economic and human burden on patients and society. FM severity level was significantly associated with patients' health status and core symptom domains.

The comparative burden of mild, moderate and severe fibromyalgia: results from a cross-sectional survey in the United States.

BACKGROUND: Fibromyalgia (FM) is characterized by chronic, widespread pain, fatigue, and other symptoms; yet few studies have comprehensively assessed its humanistic burden. This observational study evaluates the impact of FM severity on patients' symptoms, health-related quality of life (HRQoL), and productivity in the United States. METHODS: 203 FM subjects were recruited from 20 physician offices. Subjects completed a questionnaire including the EuroQol 5D (EQ-5D), Fibromyalgia Impact Questionnaire (FIQ), Multidimensional Assessment of Fatigue (MAF), Medical Outcomes Study Sleep Scale (MOS-SS), and Hospital Anxiety and Depression Scale (HADS) and questions about demographics, pain and other symptoms, HRQoL and productivity. FIQ total scores were used to define FM severity, with 0- < 39, 39- < 59, and 59-100, representing mild, moderate, and severe FM, respectively. Sites recorded subjects' clinical characteristics and FM treatment on case report forms using medical records. Summary statistics were calculated for continuous variables and frequency distributions for categorical variables. Differences across FM severity groups were evaluated using the Kruskal-Wallis or Chi-square tests. Statistical significance was evaluated at the 0.05 level. RESULTS: Mean (SD) age was 47.9 (10.9); 95% were female. Most (92%) were prescribed medication for FM; 24% and 66% reported moderate and severe FM, respectively. Mean (SD) scores were: 6.3 (2.1) for pain intensity; 0.35 (0.35) for EQ-5D; 30.7 (14.2) for MAF; 57.5 (18.4) for MOS-SS Sleep Problems Index; 10.2 (4.8) for HADS anxiety and 9.4 (4.4) for HADS depression. Subjects with worse FM severity reported significantly increased pain severity, HRQoL, fatigue, sleep disturbance, anxiety and depression (p < 0.001). Overall, 50% of subjects reported some disruption in their employment due to FM; this differed across severity levels (p < 0.001). Employed subjects missed a mean (SD) of 1.8 (3.9) workdays during the past 4 weeks; this also differed across severity levels (p = 0.03). CONCLUSIONS: FM imposes a substantial humanistic burden on patients in the United States, and leads to substantial productivity loss, despite treatment. This burden is higher among subjects with worse FM severity.

Relationships between changes in pain severity and other patient-reported outcomes: an analysis in patients with posttraumatic peripheral neuropathic pain.

BACKGROUND: The objective of this study is to use the pain numeric rating scale (NRS) to evaluate associations between change in pain severity and changes in sleep, function, and mood assessed via patient-reported outcomes (PROs) in patients with posttraumatic pain. METHODS: This is a secondary analysis of a clinical trial evaluating pregabalin in patients with posttraumatic peripheral neuropathic pain (N = 254). Regression models were used to determine associations between changes in pain (0-10 NRS) as the predictor and scores on the following PRO measures as the outcome: Pain Interference Index; Hospital Anxiety and Depression Scale anxiety and depression subscales; Medical Outcomes Study-Sleep Scale 9-item Sleep Problems Index and Sleep Disturbance subscale; and Daily Sleep Interference Scale (0-10 NRS). RESULTS: Change in pain severity showed clear, direct relationships with changes in function, anxiety, depression, and sleep PROs, all of which were statistically significant (P <.001). Results from subgroup analyses (≥30% or ≥50% pain responders, pregabalin or placebo treatment, age ≤ 51 years or > 51 years) tended to be consistent with results from the overall sample. CONCLUSIONS: Overall, a direct relationship exists between pain and various aspects of patient's well-being and functioning, which can provide a quantitative assessment of how improvements in pain may be expected to relate to other patient outcomes. (http://ClinicalTrials.gov Identifier number NCT00292188; EudraCT #2005-003048-78).

Applying area-under-the-curve analysis to enhance interpretation of response profiles: an application to sleep quality scores in patients with fibromyalgia.

PURPOSE: To introduce an application of area-under-the-curve (AUC) that can enrich interpretation of response analysis and illustrate this method on sleep quality scores in patients with fibromyalgia. METHODS: Data were from a 14-week, randomized trial conducted in 750 patients with fibromyalgia treated with placebo or pregabalin (300, 450, or 600 mg/day); sleep quality was assessed daily by the patient using an 11-point numeric rating scale. RESULTS: Response profiles were implemented for responders who improved (or stayed the same) numerically in sleep quality scores from baseline to week 14 and, separately, for non-responders who worsened (numerically less favorable scores at week 14). Differences between pregabalin and placebo were assessed using an AUC analysis. Improvement in sleep quality was significantly better with pregabalin and can be interpreted as if pregabalin responders improved by 10.8% (300 mg), 14.7% (450 mg), and 19.0% (600 mg) above the placebo responders. Conversely, decrement in sleep quality was worse with placebo and can be interpreted as if placebo non-responders worsened by 3.6% (300 mg), 2.9% (450 mg), and 3.9% (600 mg) over pregabalin non-responders. CONCLUSIONS: The application of an AUC analysis to response profiles for responders and non-responders can enrich the interpretation of sleep quality scores in patients with fibromyalgia. The method can be applied more generally to facilitate and enhance the interpretation of treatment differences on outcomes.

Correlations between fibromyalgia symptom and function domains and patient global impression of change: a pooled analysis of three randomized, placebo-controlled trials of pregabalin.

OBJECTIVE: The objective of the study was to conduct an analysis of pooled data from pregabalin fibromyalgia clinical trials to determine which fibromyalgia symptom and function domains drive patient perception of improvement. DESIGN: Data from three double-blind, placebo-controlled trials of pregabalin in fibromyalgia patients were pooled for this analysis. Changes in independent variables, including the Medical Outcomes Study 36-item Short-Form Health Survey, Medical Outcomes Study-Sleep Scale, sleep quality score from the daily sleep diary, pain score from the daily pain diary, Fibromyalgia Impact Questionnaire, and Multidimensional Assessment of Fatigue were analyzed as predictors of outcome on the dependent variable, Patient Global Impression of Change (PGIC). Correlation analysis assessed relationships between the independent variables and PGIC. Cluster analysis identified dependencies among variables, and a shrinkage and selection method and stepwise logistic regression determined rank order of variables. RESULTS: Improvement in PGIC at endpoint showed highest correlation with pain improvement, fatigue, sleep, and work and physical function (0.4 < r < 0.6). Cluster analysis identified three main clusters of symptoms at endpoint: mood (anxiety and depression), pain and sleep, and function and fatigue. Pain was ranked as the most important outcome explaining variability in PGIC, followed by fatigue and sleep. CONCLUSIONS: Pain, fatigue, and sleep associate most strongly with improvement in PGIC. Physical- and work-related function also correlated with patients' overall assessment of improvement. These domains and their respective outcome measures can be used to improve assessment of patients' response to treatment.

Retrospective evaluation of clinical characteristics, pharmacotherapy and healthcare resource use among patients prescribed pregabalin or duloxetine for diabetic peripheral neuropathy in usual care.

OBJECTIVE: To evaluate treatment patterns and costs among patients with painful diabetic peripheral neuropathy (pDPN) newly prescribed pregabalin or duloxetine in usual care settings. METHODS: Using the PharMetrics® Database, patients with pDPN (ICD-9-CM codes 357.2 or 250.6x) newly prescribed pregabalin or duloxetine were identified. Patients initiated on duloxetine (n=713; mean age 55.4 ± 9.5 years) were propensity score-matched with patients initiated on pregabalin (n=713; mean age 56.3 ± 9.3 years). Prevalence of comorbidities, pain-related pharmacotherapy and healthcare resource use/costs (pharmacy, outpatient, inpatient, total) were examined during the 12 months preceding (pre-index) and following (follow-up) the date of the first pregabalin or duloxetine prescription. RESULTS: Both cohorts had multiple comorbidities and a substantial pain medication burden. Among pregabalin patients, use of other anticonvulsants (35.6% vs. 24.7%) and tricyclic antidepressants significantly decreased (18.2% vs. 13.7%) and serotonin-norepinephrine reuptake inhibitors (SNRIs) increased (7.9 % vs. 12.9%) in the follow-up period; all P values <0.05. Among duloxetine patients, use of other SNRIs (8.7% vs. 5.2%) and selective serotonin reuptake inhibitors decreased significantly (32.1% vs. 18.9%) in the follow-up period, but there were increases for anticonvulsants (42.1% vs. 48.4%), benzodiazepines (25.5% vs. 32%), and sedative/hypnotics (22.6% vs. 25.8%); all P values <0.05. Among pregabalin and duloxetine patients there were increases (P<0.05) in pharmacy, outpatient, and total healthcare costs from the pre-index to the follow-up period. Total medication costs in the follow-up period were significantly higher for duloxetine (median $6,763 [IQR $3,970-$10,914]) relative to pregabalin (median $6,059 [IQR $3,277-$9,865]); P=0.0017. CONCLUSIONS: Patients with pDPN prescribed pregabalin and duloxetine were characterized by a substantial comorbidity and pain medication burden. Although there were no differences in total healthcare costs, medication costs were significantly higher in the duloxetine cohort relative to the pregabalin cohort.

Clinical characteristics, pharmacotherapy, and healthcare resource use among patients with diabetic neuropathy newly prescribed pregabalin or gabapentin.

OBJECTIVE: To characterize comorbidities, pain-related pharmacotherapy, and healthcare resource use among patients with painful diabetic peripheral neuropathy (pDPN) newly prescribed pregabalin or gabapentin in clinical practice. METHODS: Using the LifeLink(™) Health Plan Claims Database, patients with pDPN (ICD-9-CM codes 357.2 or 250.6) newly prescribed (index event) gabapentin (n = 1,178; 56.9 ± 10.3 years old) were identified and propensity score-matched with patients initiated on pregabalin (n = 1,178; 56.4 ± 9.8 years old). Comorbidities, pain-related pharmacotherapy, and healthcare resource use/costs were examined during the 12-month pre-index and follow-up periods. RESULTS: Both cohorts were characterized by multiple comorbidities and substantial use of pain-related and adjunctive medications. In the pregabalin cohort, the use of tricyclic antidepressants significantly decreased (16.0% vs. 13.2%) and nonsteroidal anti-inflammatory drugs (30.8% vs. 34.8%), muscle relaxants (19.2% vs. 22.9%), anticonvulsants (14.4% vs. 18.1%), benzodiazepines (22.3% vs. 25.0%), and topical agents (7.0% vs. 9.8%) increased (P < 0.05) in the follow-up period. In the gabapentin cohort, there were significant increases (P < 0.05) in the use of short-acting (55.4% vs. 61.2%) and long-acting (9.4% to 12.8%) opioids, serotonin-norepinephrine re-uptake inhibitors (14.2% vs. 16.7%), anticonvulsants (7.1% vs. 19.2%), benzodiazepines (19.1% vs. 24.3%), sedative/hypnotics (14.9% vs. 18.0%), and tramadol (13.3% vs. 16.8%). There were significant increases (P < 0.05) in pharmacy, outpatient, and total costs in both cohorts and in costs of physician office visits in the gabapentin cohort. There was no difference in postindex median total costs between the pregabalin and gabapentin cohorts ($16,137 vs. $15,766). CONCLUSIONS: Patients with pDPN prescribed pregabalin and gabapentin had a substantial comorbidity and pain medication burden. Although healthcare costs increased in both groups, the increase in pain medication burden was higher in the gabapentin group. Direct medical costs were similar for both groups. Given the human and economic burden of pDPN, future research may benefit from a focus on efficacy parameters to further differentiate treatment options.

Newly diagnosed exudative age-related macular degeneration treated with pegaptanib sodium monotherapy in US community-based practices: medical chart review study.

BACKGROUND: Studies have shown that early detection and treatment of neovascular age-related macular degeneration (NV-AMD) can delay vision loss and blindness. The objective of this study was to evaluate the efficacy/safety of intravitreal pegaptanib sodium monotherapy in treatment-naïve subjects with newly diagnosed NV-AMD and to gain insight into characteristics of lesions treated in community-based practices. METHODS: From seven private US practices, charts were retrospectively reviewed on 73 subjects with previously untreated subfoveal choroidal NV-AMD treated with their first dose of pegaptanib monotherapy on/after 4/1/2005 through 6/5/2006, receiving > or =4 treatments at 6-week intervals over 21 weeks. Primary endpoint: mean visual acuity (VA) change from baseline to month 6. RESULTS: 75% of lesions were occult, and 82% were subfoveal. From baseline to month 6, mean VA change was -0.68 lines; 58% and 16% gained > or =0 and > or =3 lines of VA, and 70% were responders (<3 lines lost). In 35 subjects with early disease, 80% were responders with a mean gain of 0.46 lines. CONCLUSION: Pegaptanib is effective in real-world patients with treatment-naïve NV-AMD in uncontrolled community-based retina practices.

Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of blindness in Western countries. Numerous risk factors have been reported but the evidence and strength of association is variable. We aimed to identify those risk factors with strong levels of evidence which could be easily assessed by physicians or ophthalmologists to implement preventive interventions or address current behaviours. METHODS: A systematic review identified 18 prospective and cross-sectional studies and 6 case control studies involving 113,780 persons with 17,236 cases of late AMD that included an estimate of the association between late AMD and at least one of 16 pre-selected risk factors. Fixed-effects meta-analyses were conducted for each factor to combine odds ratio (OR) and/or relative risk (RR) outcomes across studies by study design. Overall raw point estimates of each risk factor and associated 95% confidence intervals (CI) were calculated. RESULTS: Increasing age, current cigarette smoking, previous cataract surgery, and a family history of AMD showed strong and consistent associations with late AMD. Risk factors with moderate and consistent associations were higher body mass index, history of cardiovascular disease, hypertension, and higher plasma fibrinogen. Risk factors with weaker and inconsistent associations were gender, ethnicity, diabetes, iris colour, history of cerebrovascular disease, and serum total and HDL cholesterol and triglyceride levels. CONCLUSIONS: Smoking, previous cataract surgery and a family history of AMD are consistent risk factors for AMD. Cardiovascular risk factors are also associated with AMD. Knowledge of these risk factors that may be easily assessed by physicians and general ophthalmologists may assist in identification and appropriate referral of persons at risk of AMD.

Burden of anemia in patients with osteoarthritis and rheumatoid arthritis in French secondary care.

BACKGROUND: Arthritic disorders can be the cause of hospitalizations, especially among individuals 60 years and older. The objective of this study is to investigate associations between health care resource utilization in arthritis patients with and without concomitant anemia in a secondary care setting in France. METHODS: This retrospective cohort study utilized data on secondary care activity in 2001 from the Programme de Médicalisation des Systèmes d'Information database. Two cohorts were defined using ICD-10 codes: patients with an arthritis diagnosis with a concomitant diagnosis of anemia; and arthritis patients without anemia. Health care resource utilization for both populations was analyzed separately in public and private hospitals. Study outcomes were compared between the cohorts using standard bivariate and multivariable methods. RESULTS: There were 300,865 hospitalizations for patients with arthritis only, and 2,744 for those with concomitant anemia. Over 70% of patients with concomitant anemia were in public hospitals, compared with 53.5% of arthritis-only patients. Arthritis patients without anemia were younger than those with concomitant anemia (mean age 66.7 vs 74.6, public hospitals; 67.1 vs 72.2, private hospitals). Patients with concomitant anemia/arthritis only had a mean length of stay of 11.91 (SD 14.07)/8.04 (SD 9.93) days in public hospitals, and 10.68 (SD 10.16)/9.83 (SD 7.76) days in private hospitals. After adjusting for confounders, the mean (95% CI) additional length of stay for arthritis patients with concomitant anemia, compared with those with arthritis only, was 1.56 (1.14-1.98) days in public and 0.69 (0.22-1.16) days in private hospitals. Costs per hospitalization were €;480 (227-734) greater for arthritis patients with anemia in public hospitals, and €;30 (-113-52) less in private hospitals, than for arthritis-only patients. CONCLUSIONS: Arthritis patients with concomitant anemia have a longer length of stay, undergo more procedures, and have higher hospitalization costs than nonanemic arthritis patients in public hospitals in France. In private hospitals, concomitant anemia was associated with modest increases in length of stay and number of procedures; however, this did not translate into higher costs. Such evidence of anemia-related health care utilization and costs can be considered as a proxy for the clinical significance of anemia.

Evaluation of the safety and efficacy of pregabalin in older patients with neuropathic pain: results from a pooled analysis of 11 clinical studies.

BACKGROUND: Older patients are typically underrepresented in clinical trials of medications for chronic pain. A post hoc analysis of multiple clinical studies of pregabalin in patients with painful diabetic peripheral neuropathy (DPN) or postherpetic neuralgia (PHN) was conducted to evaluate the efficacy and safety of pregabalin in older patients. METHODS: Data from 11 double-blind, randomized, placebo-controlled clinical studies of pregabalin in patients with DPN or PHN were pooled. Efficacy outcomes included change in Daily Pain Rating Scale score, ≥30% and ≥50% responders, and endpoint pain score ≤3. Safety was based on adverse events (AEs). Primary efficacy was analyzed by analysis of covariance with terms for treatment, age category, protocol, baseline pain, and treatment-by-age category interaction. RESULTS: 2516 patients (white, n = 2344 [93.2%]; men, n = 1347 [53.5%]; PHN, n = 1003 [39.9%]; pregabalin, n = 1595) were included in the analysis. Patients were grouped by age: 18 to 64 years (n = 1236), 65 to 74 years (n = 766), and ≥75 years (n = 514). Baseline mean pain and sleep interference scores were comparable across treatment and age groups. Significant improvements in endpoint mean pain were observed for all pregabalin dosages versus placebo in all age groups (p ≤ 0.0009), except for the lowest dosage (150 mg/day) in the youngest age group. Clinically meaningful pain relief, defined as ≥30% and ≥50% pain response, was observed in all age groups. The most common AEs were dizziness, somnolence, peripheral edema, asthenia, dry mouth, weight gain, and infections. The relative risks for these AEs increased with pregabalin dose, but did not appear related to older age or type of neuropathic pain. CONCLUSIONS: Pregabalin (150-600 mg/day) significantly reduced pain in older patients (age ≥65 years) with neuropathic pain and improvements in pain were comparable to those observed in younger patients. Titration of pregabalin to the lowest effective dose should allow for effective pain relief while minimizing AEs in older patients with neuropathic pain. Given the common use of polypharmacy in older patients, the absence of known drug-drug interactions makes pregabalin an important treatment option for older patients with pain of neuropathic origin.

Toward characterization and definition of fibromyalgia severity.

BACKGROUND: There are no standard criteria for defining or assessing severity of fibromyalgia (FM) as a condition as fibromyalgia is associated with multiple symptom domains. The objective of this study was to evaluate whether patient self-reported severity of FM is associated with severity of pain and sleep interference and the presence of core co-morbidities. METHODS: We recruited individuals >or= 18 years of age with a clinician-confirmed diagnosis of FM >or= 3 months and a current pain rating >2 on a 0-10 numeric rating scale (NRS). Patients completed a questionnaire by mail in which they self-rated their FM severity (very mild, mild, moderate, and severe), their current pain severity and extent of sleep interference (NRS; mild, 0-3; moderate, 4-6, severe, 7-10), and provided information (yes/no) on the presence of core comorbidities (symptoms of depression, anxiety, sleep problems, back pain, neck pain) and medication use for FM. The core symptoms of FM were stratified to assist with patient characterization. Analysis of variance (ANOVA) was used to explore the relationship between self-reported FM severity and continuous variables (pain severity and sleep interference), and Mantel-Haenszel chi-square analysis was used to evaluate the trend in the proportions of patients reporting use of medications and core symptoms of FM by severity of FM. To complement patient-reported FM severity and to understand physicians' perspectives, a survey was performed among 28 physician specialists (rheumatology, neurology, anesthesiology/pain management, family practice, internal medicine, and psychiatry) to determine what they assessed when evaluating FM severity in clinical practice. RESULTS: The population (N = 129) of FM patients was predominantly female (89.1%), with a mean age of 49.4 +/- 11.0 years, and 81.4% reported duration >or= 2 years. Self-reported FM severity was moderate/severe in 86.0% of patients; mean current pain score was 6.40 +/- 2.19 (moderate), and mean sleep interference score was 7.28 +/- 2.23 (severe). Greater FM severity was significantly associated with higher levels of current pain and sleep interference (p < 0.0001), the proportion of patients reporting FM medication use (p = 0.0001), and the presence of core comorbidities (p < 0.05). Pain, functional disability, and fatigue severity were ranked as the top three criteria by the highest proportion of physicians when evaluating FM severity. CONCLUSION: With higher self-reported FM severity, patients have greater pain and sleep interference as well as increased frequency of core comorbidities. Further investigation into understanding FM severity is warranted.

Identification of symptom and functional domains that fibromyalgia patients would like to see improved: a cluster analysis.

BACKGROUND: The purpose of this study was to determine whether some of the clinical features of fibromyalgia (FM) that patients would like to see improved aggregate into definable clusters. METHODS: Seven hundred and eighty-eight patients with clinically confirmed FM and baseline pain > or =40 mm on a 100 mm visual analogue scale ranked 5 FM clinical features that the subjects would most like to see improved after treatment (one for each priority quintile) from a list of 20 developed during focus groups. For each subject, clinical features were transformed into vectors with rankings assigned values 1-5 (lowest to highest ranking). Logistic analysis was used to create a distance matrix and hierarchical cluster analysis was applied to identify cluster structure. The frequency of cluster selection was determined, and cluster importance was ranked using cluster scores derived from rankings of the clinical features. Multidimensional scaling was used to visualize and conceptualize cluster relationships. RESULTS: Six clinical features clusters were identified and named based on their key characteristics. In order of selection frequency, the clusters were Pain (90%; 4 clinical features), Fatigue (89%; 4 clinical features), Domestic (42%; 4 clinical features), Impairment (29%; 3 functions), Affective (21%; 3 clinical features), and Social (9%; 2 functional). The "Pain Cluster" was ranked of greatest importance by 54% of subjects, followed by Fatigue, which was given the highest ranking by 28% of subjects. Multidimensional scaling mapped these clusters to two dimensions: Status (bounded by Physical and Emotional domains), and Setting (bounded by Individual and Group interactions). CONCLUSION: Common clinical features of FM could be grouped into 6 clusters (Pain, Fatigue, Domestic, Impairment, Affective, and Social) based on patient perception of relevance to treatment. Furthermore, these 6 clusters could be charted in the 2 dimensions of Status and Setting, thus providing a unique perspective for interpretation of FM symptomatology.

Identifying fibromyalgia-associated symptoms and conditions from a clinical perspective: a step toward evaluating healthcare resource utilization in fibromyalgia.

OBJECTIVE: The study aims to determine from the physician's perspective, the conditions and symptoms most relevant to the diagnosis of fibromyalgia (FM) for identifying International Classification of Diseases-diagnosis codes and prescription medications to evaluate FM-related healthcare resource utilization. METHODS: A questionnaire was administered using an online physician network (SERMO™) from which responses of 102 physicians were evaluated: anesthesiologists (n = 6), neurologists (n = 18), primary care physicians (n = 16), pain specialists (n = 16), psychiatrists (n = 15), and rheumatologists (n = 31). Physicians scored the relative importance to a diagnosis of FM (0 = least relevant/important, 10 = most relevant/important) of 24 conditions and symptoms derived from a list provided by the National Data Bank for Rheumatic Diseases. Conditions and symptoms with mean scores ≥ 5 were considered the most relevant. Other survey questions included treatment goals, assessment of disease severity, medication use, and characterization of the physicians' experience and clinical practice. RESULTS: Ten conditions and symptoms (mean score) were reported as most relevant: Muscle pain (8.7), Fatigue/tiredness (8.5), Insomnia (8.0), Depression (7.8), Thinking/remembering (6.7), Nervousness (6.0), Muscle weakness (5.9), Headache (5.7), Irritable bowel syndrome (5.5), and Pain/cramps in abdomen (5.1). Treatment goals, severity assessment, and use of medications were generally similar across physician specialties. CONCLUSIONS: This survey identified 10 conditions and symptoms that physician respondents considered most relevant to a diagnosis of FM. Further evaluation to determine how these conditions and symptoms contribute to FM-associated healthcare resource utilization is warranted.

Evaluation of the impact of fibromyalgia on patients' sleep and the content validity of two sleep scales.

BACKGROUND: Disturbed sleep is commonly reported in fibromyalgia (FM). Both the Sleep Quality Numeric Rating Scale (NRS) and the Medical Outcomes Study Sleep Scale (MOS-Sleep) have demonstrated positive psychometric properties in patients with FM. However, these assessments were developed prior to the current recommendation to include patient input during the concept elicitation or item generation phases. Therefore, the objective of this study was to evaluate the impact of FM on participants, including their sleep, and to test the content validity of these two sleep measures in FM patients. METHODS: Qualitative interviews were conducted in Raleigh, North Carolina and Detroit, Michigan with 20 adults who reported a physician diagnosis of FM. Sixteen participants were female, 13 were white, and the average age was 50 years. Two researchers conducted all interviews using a structured guide. RESULTS: Participants consistently reported that FM had a debilitating impact on their lives and their sleep, particularly getting to sleep and staying asleep. Participants responded positively to the Sleep Quality NRS as an assessment of their sleep. The majority of participants stated that they would not change the response numbering or wording of the item's anchors. Participants also responded positively to the 24-hour recall period of the Sleep Quality NRS. Participants found the 12-item MOS-Sleep to be appropriate and relevant; 19 participants indicated the measure captured all of their sleep-related symptoms. However, areas for potential modification were identified, such as the need to separate the item regarding awakening short of breath and awakening with a headache into two separate questions. Participants also questioned the relevance of the snoring and awakening short of breath items to FM. Half of participants expressed a preference for a daily rather than a weekly recall period. CONCLUSION: This study demonstrates the significant impact that FM has on patients' lives, particularly sleep. While patients with FM were not part of the development of the generic sleep assessments that were evaluated, this study provides evidence of their content validity, supporting their use in FM studies. Modifications to the MOS-Sleep may improve the psychometric properties and relevance to patients with FM.

Reduction in opioid-related adverse events and improvement in function with parecoxib followed by valdecoxib treatment after non-cardiac surgery: a randomized, double-blind, placebo-controlled, parallel-group trial.

BACKGROUND: Multimodal pain therapy including cyclo-oxygenase-2 inhibitors can result in optimal pain management with decreased opioid use and fewer opioid-related adverse events. Patient reported outcomes (PROs) help identify benefits in reduced opioid use and increased pain control. METHODS: In this randomized, double-blind trial, patients (n = 1062) undergoing major non-cardiac elective surgery received either parenteral parecoxib for 3 days or placebo then oral valdecoxib or placebo for a total of 10 days, with both arms being allowed additional opioid analgesia. Clinically meaningful opioid-related adverse events were assessed daily using the Opioid-Related Symptom Distress Scale (OR-SDS). Pain severity and interference with function were evaluated daily using the modified Brief Pain Inventory exploratory form (mBPI-e). Additional validation work was undertaken to understand the psychometric properties of the two PROs. Detailed clinical results were reported elsewhere. RESULTS: Patients receiving parecoxib/valdecoxib achieved significantly better pain control and consumed 37% and 28% less opioid medication than the placebo group on day 2 and day 3, respectively. Over the 10-day treatment period, patients receiving parecoxib/valdecoxib consumed 31% less opioid medication. This coincided with significantly fewer (p < 0.0001) OR-SDS clinically meaningful events (CMEs) and lower mBPI-e scores from days 2-10 in the parecoxib/valdecoxib group compared with the placebo group. On day 3, the percentage of patients reporting one, two or three CMEs in the parecoxib/valdecoxib versus placebo group was 11.6% versus 13.0%, 2.3% versus 5.1%, and 0.8% versus 2.3%, respectively. The mean (+/- standard error) mBPI-e pain severity scores over days 2-10 were 2.47 +/- 0.04 for the parecoxib/valdecoxib group and 3.01 +/- 0.04 for the placebo group, and the mean mBPI-e pain interference scores were 1.73 +/- 0.04 and 2.19 +/- 0.04, respectively. CONCLUSIONS: Patients receiving parecoxib/valdecoxib had less pain interference on physical functioning, required less opioid medication and experienced fewer clinically meaningful opioid-related adverse events than patients receiving placebo.

Cost-utility of celecoxib use in different treatment strategies for osteoarthritis and rheumatoid arthritis from the Quebec healthcare system perspective.

OBJECTIVE: To assess the cost-utility of celecoxib in three treatment strategies for arthritis in Quebec, considering both upper gastrointestinal (GI) and cardiovascular (CV) events. METHODS: A Markov analytic framework was used to model patients with osteoarthritis and rheumatoid arthritis at low/average and high risk of GI and CV toxicity over 5 years with monthly cycles. Treatment strategies were modelled in line with Canadian clinical practice. In first-line treatment, patients started on celecoxib; second-line, patients started on a non-selective non-steroidal anti-inflammatory drug (NSAID) and switched to celecoxib after a first GI event; third-line, patients started on a non-selective NSAID, added a proton pump inhibitor (PPI) after a first GI event, and switched to celecoxib after a second GI event (while maintaining the PPI). Model inputs were determined through comprehensive literature searches (MEDLINE and EMBASE) from 1995 to 2006. Included studies evaluated GI (dyspepsia, uncomplicated and complicated ulcers, death) and CV (myocardial infarction, stroke, death) events. Drug and procedure costs were derived from Canadian published sources (Can$2005). RESULTS: Total costs per patient for celecoxib first-, second-, and third-line treatment were Can$4,790, $3,390, and $3,466, and total quality-adjusted life-years (QALY) were 3.251, 3.231, and 3.230, respectively. In all risk categories, celecoxib second-line was less costly and as effective as celecoxib third-line, producing savings to the healthcare system. Although celecoxib first-line generated incremental expenditures versus celecoxib second-line, it was also more effective. The resulting cost-utility ratio for the high-risk population was Can$54,696/QALY. Based on this analytical approach, a treatment strategy where celecoxib is used before the combination of a non-selective NSAID plus a PPI possesses cost advantages for the Quebec provincial drug programme. One-way sensitivity analysis (varying GI and CV event rates, utilities, and cost) generally showed second-line treatment with celecoxib as the dominant strategy compared with third-line treatment with celecoxib. CONCLUSION: Although effectiveness of second- and third-line celecoxib use is similar, total cost is lower for second-line. These results suggest that the use of celecoxib before the combination of a non-selective NSAID plus a PPI is relatively cost-effective in the treatment of arthritis pain and support the full benefit listing of celecoxib in Quebec's drug programme.