Interpreting the Effectiveness of Opioids and Pregabalin for Pain Severity, Pain Interference, and Fatigue in Fibromyalgia Patients.

OBJECTIVE: To evaluate the effectiveness of opioids and/or pregabalin on patient-reported outcomes among fibromyalgia (FM) patients based on levels of improvement. METHODS: A total of 1,421 FM patients were identified, with 3,082 observational periods of opioids with or without pregabalin use between April 2008 and February 2015. Patients were categorized by opioids, and pregabalin with and without opioids; opioids were designated by morphine equivalent dose (MED) of ≤ 20 (low MED), > 20 to < 100 (moderate MED), ≥ 100 (high MED), and pregabalin doses of ≤ 150 mg, 151 to 300 mg, and 301 to 450 mg. Proportions of patients meeting clinically relevant thresholds of ≥ 30% and ≥ 50% improvement for pain interference (ability to enjoy life; activity; mood; relationships; sleep), pain severity, and fatigue were compared among treatments, and area under the curve (AUC) for improvement and worsening of effects was determined, enabling ranking of treatments. Further analysis compared pregabalin doses. RESULTS: Pregabalin without opioids resulted in the highest proportions of patients with ≥ 30% improvement on all pain items and pain interference with "ability to enjoy life," "activity" "mood," and "sleep." For the ≥ 50% threshold, pregabalin alone was highest for all pain interference items and for "average pain" and "worst pain." Pregabalin was consistently lowest across thresholds for fatigue, but showed better results combined with moderate MED opioids. Pregabalin doses recommended for treatment of FM (151 to 450 mg) generally resulted in the highest proportion of patients achieving thresholds relative to opioids. The AUC results were consistent with thresholds; pregabalin without opioids resulted in the greatest benefits with regard to improvement, with the highest ranking for overall improvement and overall effects. CONCLUSION: Pregabalin without opioids provided the most favorable outcomes overall based on ≥ 30% and ≥ 50% improvement thresholds and AUC, with support for moderate MED opioids + pregabalin in patients suffering from fatigue. While most patients took less than recommended pregabalin doses, higher doses may lead to improved outcomes.

Clinical Characteristics of Fibromyalgia in a Chronic Pain Population.

OBJECTIVE: To compare fibromyalgia (FM) characteristics among patients identified in a community-based chronic pain cohort based on traditional International Classification of Diagnoses 9th revision (ICD-9) diagnostic coding, with that of patients identified using a novel predictive model. METHODS: This retrospective study used data collected from July 1999 to February 17, 2015, in multiple chronic pain clinics in the United States. Patients were assigned to the FM case group based on specific inclusion criteria using ICD-9 codes or, separately, from results of a novel FM predictive model that was developed using random forest and logistic regression techniques. Propensity scoring (1:1) matched FM patients (cases) to nonmalignant chronic pain patients without FM (controls). Patient-reported measures (eg, pain, fatigue, quality of sleep) and clinical characteristics (ie, comorbidities, procedures, and regions of pain) were outcomes for analysis. RESULTS: Nine ICD-9 clinical modification diagnoses had odds ratios with large effect sizes (Cohen's d > 0.8), demonstrating the magnitude of the difference between the FM and matched non-FM cohorts: chronic pain syndrome, latex allergy, muscle spasm, fasciitis, cervicalgia, thoracic pain, shoulder pain, arthritis, and cervical disorders (all P < 0.0001). Six diagnoses were found to have a moderate effect size (Cohen's 0.5 < d > 0.8): cystitis, cervical degeneration, anxiety, joint pain, lumbago, and cervical radiculitis. CONCLUSIONS: The identification of multiple comorbidities, diagnoses, and musculoskeletal procedures that were significantly associated with FM may facilitate differentiation of FM patients from other conditions characterized by chronic widespread pain. Predictive modeling may enhance identification of FM patients who may otherwise go undiagnosed.

Measurement properties of painDETECT: Rasch analysis of responses from community-dwelling adults with neuropathic pain.

BACKGROUND: painDETECT (PD-Q) is a self-reported assessment of pain qualities developed as a screening tool for pain of neuropathic origin. Rasch analysis is a strategy for examining the measurement characteristics of a scale using a form of item response theory. We conducted a Rasch analysis to consider if the scoring and measurement properties of PD-Q would support its use as an outcome measure. METHODS: Rasch analysis was conducted on PD-Q scores drawn from a cross-sectional study of the burden and costs of NeP. The analysis followed an iterative process based on recommendations in the literature, including examination of sequential scoring categories, unidimensionality, reliability and differential item function. Data from 624 persons with a diagnosis of painful diabetic polyneuropathy, small fibre neuropathy, and neuropathic pain associated with chronic low back pain, spinal cord injury, HIV-related pain, or chronic post-surgical pain was used for this analysis. RESULTS: PD-Q demonstrated fit to the Rasch model after adjustments of scoring categories for four items, and omission of the time course and radiating questions. The resulting seven-item scale of pain qualities demonstrated good reliability with a person-separation index of 0.79. No scoring bias (differential item functioning) was found for this version. CONCLUSIONS: Rasch modelling suggests the seven pain-qualities items from PD-Q may be used as an outcome measure. Further research is required to confirm validity and responsiveness in a clinical setting.

Mapping painDETECT, a neuropathic pain screening tool, to the EuroQol (EQ-5D-3L).

PURPOSE: To map relationships between painDETECT, a neuropathic pain (NeP) screening tool, and EQ-5D-3L health status in a real-world setting. METHODS: Patients with physician-confirmed NeP and painDETECT score classifications of nociceptive (n = 79), transitional (n = 141), and NeP (n = 386) completed the EuroQol (EQ-5D-3L), which evaluates Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression with three ordinal response levels ("no problem," "some problems," or "extreme problems/unable to do"), and has a health status thermometer (0 = worst health, 100 = perfect health). Multiple linear and logistic regressions were performed (adjusted for age, gender, race, ethnicity, time since NeP diagnosis, number of comorbidities, NeP conditions). RESULTS: Unadjusted mean (±SD) EQ-5D-3L thermometer scores showed poorer health status across painDETECT classifications from nociceptive (67.3 ± 22.1) to transitional (62.3 ± 20.9) to NeP (53.7 ± 21.8), as did utility scores, 0.695 ± 0.206, 0.615 ± 0.216, and 0.506 ± 0.216. In general, the highest odds of health problems were observed for NeP and the lowest for nociceptive, e.g., the NeP group was 6.2 (95 % confidence interval 3.4-11.4) times as likely to have a more severe problem of Usual Activities compared with the nociceptive group. Relative to nociceptive and transitional, NeP had lower adjusted mean thermometer scores, by 12.1 (P < 0.0001) and 7.8 (P = 0.0004) points, respectively, and lower mean utility scores by 0.157 (P < 0.0001) and 0.092 points (P < 0.0001). CONCLUSIONS: This study, the first to map relationships between painDETECT and the EQ-5D-3L in a real-world setting, indicates that the patient burden with respect to pain classification can be characterized and quantified by decrements in health status overall and in specific domains. These data support the psychometric soundness of painDETECT, enhancing its use in pain management.

Using Random Forest Models to Identify Correlates of a Diabetic Peripheral Neuropathy Diagnosis from Electronic Health Record Data.

Objective: To identify variables correlated with a diagnosis of diabetic peripheral neuropathy (DPN) using random forest modeling applied to electronic health records. Design: Retrospective analysis. Setting: Humedica de-identified electronic health records database. Subjects: Subjects ≥ 18 years old with type 2 diabetes from January 1, 2008-September 30, 2013 having continuous data for 1 year pre- and postindex with DPN (n = 35,050) and without DPN (n = 288,328) were identified. Methods: Demographic, clinical, and health care resource utilization variables (e.g., inpatient and outpatient encounters, medications, and procedures) were input into a random forest model to identify the most important correlates of a DPN diagnosis. Random forest modeling is a computationally extensive, robust data mining technique that accommodates large sets of variables to identify associated factors using an ensemble of classifications trees. Accuracy of the model was evaluated using receiver operating characteristic curves (ROC). Results: The final random forest model consisted of the following variables (importance) associated with a DPN diagnosis: Charlson Comorbidity Index score (100%), age (37.1%), number of pre-index procedures and services (29.7%), number of pre-index outpatient prescriptions (24.2%), number of pre-index outpatient visits (18.3%), number of pre-index laboratory visits (16.9%), number of pre-index outpatient office visits (12.1%), number of inpatient prescriptions (5.9%), and number of pain-related medication prescriptions (4.4%). ROC analysis confirmed model performance, with an area under the curve of 0.824 and accuracy of 89.6% (95% confidence interval 89.4%, 89.8%). Conclusions: Random forest modeling can determine likelihood of a DPN diagnosis. Further validation of the random forest model may help facilitate earlier diagnosis and enhance management strategies.

A systematic review of the effectiveness of policies restricting access to pregabalin.

BACKGROUND: Formularies often employ restriction policies to reduce pharmacy costs. Pregabalin, an alpha-2-delta ligand, is approved for treatment of fibromyalgia (FM); neuropathic pain (NeP) due to postherpetic neuralgia (PHN), diabetic peripheral neuropathy (pDPN), spinal cord injury; and as adjunct therapy for partial onset seizures. Pregabalin is endorsed as first-line therapy for these indications by several US and EU medical professional societies. However, restriction policies such as prior authorization (PA) and step therapy (ST) often favor less costly generic pain medications over pregabalin. METHODS: A structured literature search (PubMed, past 11 years) was conducted to evaluate whether restriction policies against pregabalin support real-world economic and healthcare utilization benefits. RESULTS: Search criteria identified three claims analyses and a modeling study that evaluated patients with NeP and/or FM with and without PA restrictions; three other studies included patients with FM and NeP in plans with ST requirements, and one evaluated a mail order requirement program. All studies evaluated outcomes during follow-up periods of 6 months or longer. Overall, PA, ST, and mail order restriction policies effectively reduced pregabalin usage, but the effects were inconsistent with reducing pharmacy costs and were non-significant for total disease-related medical costs. Two studies (one PA; one ST) reported significantly higher disease-related costs in restricted plans. The modeling study failed to demonstrate cost savings with PA. Opioid usage was higher in PA-restricted plans (two studies). The US Centers for Disease Control and Prevention and several professional NeP guidelines recommend opioid use only in cases when other non-opioid pain therapies have proven ineffective. New US Government taskforce guidelines now seek to reduce opioid exposure. Additionally, in both ST studies, gabapentin utilization (a common ST edit) was significantly increased. Both studies had substantial proportions of FM and pDPN patients and the only pain condition gabapentin is approved to treat in the United States is PHN. CONCLUSION: PA and ST restriction policies significantly decrease utilization of pregabalin, but do not consistently demonstrate cost savings for US health plans. More research is needed to evaluate whether these policies may lead to increased opioid usage as found in some studies. TRIAL REGISTRATION: N/A.

Effects of Pregabalin in Patients with Neuropathic Pain Previously Treated with Gabapentin: A Pooled Analysis of Parallel-Group, Randomized, Placebo-controlled Clinical Trials.

OBJECTIVES: This analysis compared the therapeutic response of pregabalin in patients with neuropathic pain (NeP) who had been previously treated with gabapentin to the therapeutic response in patients who had not received gabapentin previously. METHODS: Data were pooled from 18 randomized, double-blind, placebo-controlled trials of pregabalin in patients with NeP. Pregabalin-mediated changes in pain and pain-related sleep interference scores, patient global impression of change scores at endpoint, and the occurrence of adverse events were compared between patients who had received gabapentin previously (+GBN) and patients who had not received gabapentin previously (-GBN). RESULTS: There were no significant differences between the -GBN and +GBN cohorts with regard to the extent of pain relief and relief of pain-related sleep interference for any dose of pregabalin (150, 300, 600, or 150 to 600 mg/day) at any time point (6, 8, or 12 weeks). Additionally, there was no significant difference in the distribution of patient global impression of change scores at study endpoint, or the occurrence of adverse events, between the -GBN and +GBN cohorts. DISCUSSION: The findings presented here support the idea that pregabalin may be used successfully to treat patients with NeP who may be refractory, respond inadequately, or are intolerant to gabapentin. These findings highlight the importance of tailoring treatment of NeP based on individual patient response to different treatments, including the trial of multiple agents within the same mechanistic class.

A retrospective, matched cohort study of potential drug-drug interaction prevalence and opioid utilization in a diabetic peripheral neuropathy population initiated on pregabalin or duloxetine.

BACKGROUND: Anticipating and controlling drug-drug interactions (DDIs) in older patients with painful diabetic peripheral neuropaty (pDPN) presents a significant challenge to providers. The purpose of this study was to examine the impact of newly initiated pregabalin or duloxetine treatment on Medicare Advantage Prescription Drug (MAPD) plan pDPN patients' encounters with potential drug-drug interactions, the healthcare cost and utilization consequences of those interactions, and opioid utilization. METHODS: Study subjects required a pregabalin or duloxetine pharmacy claim between 07/01/2008-06/30/2012 (index event), ≥1 inpatient or ≥2 outpatient medical claims with pDPN diagnosis between 01/01/2008-12/31/2012, and ≥12 months pre- and ≥6 post-index enrollment. Propensity score matching was used to balance the pregabalin and duloxetine cohorts on pre-index demographics and comorbidities. Potential DDIs were defined by Micromedex 2.0 and identified by prescription claims. Six-month post-index healthcare utilization (HCU) and costs were calculated using pharmacy and medical claims. RESULTS: No significant differences in pre-index demographics or comorbidities were found between pregabalin subjects (n = 446) and duloxetine subjects (n = 446). Potential DDI prevalence was significantly greater (p < 0.0001) among duoxetine subjects (56.7%) than among pregabalin subjects (2.9%). There were no significant differences in HCU or costs between pregablin subjects with and without a potential DDI. By contrast, duloxetine subjects with a potential DDI had higher mean all-cause costs ($13,908 vs. $9,830; p = 0.001), more subjects with ≥1 inpatient visits (35.6% vs 25.4%; p = 0.02), and more subjects with ≥1 emergency room visits (32.8% vs. 20.7%; p = 0.005) in comparison to duloxetine subjects without a potential DDI. There was a trend toward a difference between pregabalin and duloxetine subjects in their respective pre-versus-post differences in milligrams (mg) of morphine equivalents/30 days used (60.2 mg and 176.9 mg, respectively; p = 0.058). CONCLUSION: The significantly higher prevalence of potential DDIs and potential cost impact found in pDPN duloxetine users, relative to pregabalin users, underscore the importance of considering DDIs when selecting a treatment.

Functional Impairment Is a Risk Factor for Knee Replacement in the Multicenter Osteoarthritis Study.

BACKGROUND: Debilitating pain associated with knee osteoarthritis (OA) often leads patients to seek and complete total knee arthroplasty (TKA). To date, few studies have evaluated the relation of functional impairment to the risk of TKA, despite the fact that OA is associated with functional impairment. QUESTIONS/PURPOSES: The purpose of our study was to (1) evaluate whether function as measured by WOMAC physical function subscale was associated with undergoing TKA; and (2) whether any such association varied by sex. METHODS: The National Institutes of Health-funded Multicenter Osteoarthritis Study (MOST) is an observational cohort study of persons aged 50 to 79 years with or at high risk of symptomatic knee OA who were recruited from the community. All eligible subjects with complete data were included in this analysis. Our study population sample consisted of 2946 patients with 5796 knees; 1776 (60%) of patients were women. We performed a repeated-measures analysis using baseline WOMAC physical function score to predict the risk of TKA from baseline to 30 months and WOMAC score at 30 months to predict risk of incident TKA from 30 months to 60 months. We used generalized estimating equations to account for the correlation between two knees within an individual and across the two periods. We calculated relative risk (RR) of TKA over 30 months by WOMAC function using a score of 0 to 5 as the referent in multiple binomial regressions with log link. RESULTS: Those with the greatest functional impairment (WOMAC scores 40-68; 62 TKAs in 462 knee periods) had 15.5 times (95% confidence interval [CI], 7.6-31.8; p<0.001) the risk of undergoing TKA over 30 months compared with the referent group (12 TKAs in 3604 knee periods), adjusting for basic covariates, and 5.9 times (95% CI, 2.8-12.5; p<0.001) the risk after further adjusting for knee pain severity. At every level of functional limitation, the RR for TKA for women was higher than for men, but interaction with sex did not reach significance after adjustment for covariates including ipsilateral pain (p=0.138). CONCLUSIONS: Baseline physical function appears to be an important element in patients considering TKA. Future studies should examine whether interventions to improve function can reduce the need for TKA. LEVEL OF EVIDENCE: Level III, observational cohort study.

Burden of illness associated with peripheral and central neuropathic pain among adults seeking treatment in the United States: a patient-centered evaluation.

OBJECTIVE: The aim of this study was to evaluate patient-reported burden associated with peripheral and central neuropathic pain (NeP) by pain severity and NeP condition. DESIGN: Six hundred twenty-four subjects with one of six NeP conditions were recruited during routine office visits. Subjects consented to retrospective chart review and completed a one-time questionnaire (including EuroQol-5 dimensions, 12-item Short-Form Health Survey, Brief Pain Inventory-Short Form, Medical Outcomes Study Sleep Scale, Hospital Anxiety and Depression Scale, and demographic and clinical characteristics). Pain severity scores were used to stratify subjects by mild, moderate, and severe pain. Summary statistics and frequency distributions were calculated. Differences by severity level were compared using Kruskal-Wallis (continuous variables) and chi-square or Fisher's exact test (categorical variables). Effect size was computed with Cohen's d (mild vs severe). RESULTS: Subjects' mean age was 55.5. The majority (80.8%) had moderate or severe pain. Patient-reported outcomes (health status, physical and mental health, pain interference with function, sleep, anxiety, and depression) were significantly worse among subjects with greater pain severity (all P < 0.0001). Severe pain subjects were negatively impacted by ≥30% in each outcome compared with mild pain subjects; standardized effect size was moderate for anxiety (0.59) and large (>0.95) for all others. The observed burden was most substantial among chronic low back pain-NeP, although the pattern of disease burden was similar across the six NeP conditions. CONCLUSIONS: Subjects across NeP conditions exhibited high pain levels, which were significantly associated with poor function, compromised health status and sleep, and increased anxiety and depression. Results indicate substantial patient burden across broad NeP, particularly among subjects with severe pain.

Health care resource utilization and medical costs of spinal cord injury with neuropathic pain in a commercially insured population in the United States.

OBJECTIVE: To evaluate health care resource use, costs, and cost drivers among patients with neuropathic pain (NeP) after spinal cord injury (SCI) in a commercially insured population. DESIGN: Retrospective longitudinal cohort study comparing SCI patients with and without NeP. SETTING: Truven Health MarketScan commercial claims database from 2005 through 2012. PARTICIPANTS: Commercially insured SCI patients with NeP (n=3524) propensity score matched to SCI patients without NeP (n=3524). INTERVENTIONS: Not applicable. MAIN OUTCOMES MEASURES: Health care resource utilization and expenditures for the 12 months after NeP onset (index event; identified through International Classification of Diseases, 9th Revision, Clinical Modification diagnosis 338.0x or use of NeP-specific antiepileptic drugs or NeP-specific antidepressants) in patients with SCI compared with matched patients without NeP. RESULTS: Utilization over 12 months postindex among patients with SCI-associated NeP was higher than among SCI-only patients for inpatient admissions (27.4% vs 22.1%), emergency department visits (36.7% vs 26.4%), and office visits per patient (mean ± SD: 13.0±9.5 vs 9.5±8.3); all P values were <.001. All-cause expenditures showed adjusted incremental costs of $22,545 (95% confidence interval, $19,010-$26,168) per patient with SCI-associated NeP during the 12-month postindex period. CONCLUSIONS: Patients with evidence of NeP secondary to SCI have significantly higher health care utilization and total costs compared with SCI patients without evidence of NeP. Factors contributing to NeP in patients with SCI need to be clinically assessed to determine the optimal approach for treating these individuals.

Systematic review and meta-analysis of pharmacological therapies for painful diabetic peripheral neuropathy.

BACKGROUND: Painful diabetic peripheral neuropathy (pDPN) is prevalent among persons with diabetes and increases over time. Published guidelines recommend a number of medications to treat this condition providing clinicians with a variety of treatment options. This study provides a comprehensive systematic review and meta-analysis of published pharmacologic therapies for pDPN. METHODS: The published literature was systematically searched to identify randomized, controlled trials of all available pharmacologic treatments for pDPN (recommended or nonrecommended) reporting predefined efficacy and safety outcomes. Bayesian fixed-effect mixed treatment comparison methods were used to assess relative therapeutic efficacy and harms. RESULTS: Data from 58 studies including 29 interventions and 11,883 patients were analyzed. Pain reduction over that of placebo on the 11-point numeric rating scale ranged from -3.29 for sodium valproate (95% credible interval [CrI] = [-4.21, -2.36]) to 1.67 for Sativex (-0.47, 0.60). Estimates for most treatments were clustered between 0 and -1.5 and were associated with more study data and smaller CrIs. Pregabalin (≥ 300 mg/day) was the most effective on the 100-point visual analog scale (-21.88; [-27.06, -16.68]); topiramate was the least (-3.09; [-3.99, -2.18]). Relative risks (RRs) of 30% pain reduction ranged from 0.78 (Sativex) to 1.84 (lidocaine 5% plaster). Analysis of the RR ratio of these 2 treatments reveals marginal significance for Sativex (3.27; [1.07, 9.81]), indicating the best treatment is only slightly better than the worst. Relative risks of 50% pain reduction ranged from 0.98 (0.56, 1.52) (amitriptyline) to 2.25 (1.51, 3.00) (alpha-lipoic acid). RR ratio for these treatments was not statistically different (3.39; [0.88, 3.34]). Fluoxetine had the lowest risk of adverse events (0.94; [0.62, 1.23]); oxycodone had the highest (1.55; [1.45, 1.64]). Discontinuation RRs were clustered around 0.8 to 1.5, with those on the extreme having greater uncertainty. CONCLUSIONS: Selecting an appropriate pDPN therapy is key given the large number of available treatments. Comparative results revealed relative equivalence among many of the studied interventions having the largest overall sample sizes and highlight the importance of standardization of methods to effectively assess pain.

Relationship between self-reported low-back pain severity and other patient-reported outcomes: results from an observational study.

STUDY DESIGN: A cross-sectional observational study of physicians and patients with chronic low-back pain (CLBP) in the United States. OBJECTIVE: To evaluate the association of patient-reported CLBP severity with other patient-reported outcomes. SUMMARY OF BACKGROUND DATA: Appropriate management of patients with CLBP can be enhanced by understanding how patients perceive the severity of their CLBP. METHODS: Data were from the 2009 Adelphi Disease Specific Programme. Patients reported the severity of their CLBP condition by answering the question Please rate how your chronic lower back pain condition is today with responses of mild, moderate, and severe. Patient-reported severity was evaluated with respect to scores on standard patient self-report measures of pain, pain interference, health status, functional disability, work productivity, and questions addressing satisfaction with medications for treating CLBP. RESULTS: Of 1860 subjects in the CLBP database, 1363 (73.3%) agreed to complete the survey. This sample was similarly distributed between males (49%) and females (51%), with mean age 54.8 years: 52% were employed at least part-time. CLBP severity was rated as mild, moderate and severe by 28.6%, 53.3%, and 18.2% of patients, respectively. With increasing CLBP severity, significant differences were observed in increased pain (P<0.0001), pain interference with function (P<0.0001), and impairment while working due to CLBP (P<0.01), mainly due to presenteeism. Increased work impairment resulted in higher costs related to lost work productivity; annual lost productivity costs were estimated at $7080, $16,616, and $25,032 per patient for mild, moderate, and severe CLBP, respectively (P<0.0001 for pairwise comparisons). Patient satisfaction with pain-related medication was inversely associated with CLBP severity. CONCLUSIONS: The association between patient-reported CLBP severity and other patient-reported outcomes demonstrates that in the clinical setting, patient-reported CLBP severity provides an accurate and suitable indicator of patient-reported health status. This indicator may be useful for guiding management strategies for CLBP patients.

Clinical characteristics and patterns of healthcare utilization in patients with painful neuropathic disorders in UK general practice: a retrospective cohort study.

BACKGROUND: Clinical characteristics and patterns of healthcare utilization in patients with painful neuropathic disorders (PNDs) who are under the care of general practitioners (GPs) in the UK are not well understood. METHODS: Using a large electronic UK database, we identified all adults (age ≥ 18 years) with any GP encounters between 1 January 2006-31 December 2006 at which a diagnosis of PND was noted ("PND patients"). An age-and gender-matched comparison group also was constituted consisting of randomly selected patients with one or more GP encounters-but no mention of PNDs-during this period. Characteristics and patterns of healthcare utilization of patients in the two groups were then examined over the one-year study period. RESULTS: The study sample consisted of 31,688 patients with mention of PNDs and an equal number of matched comparators; mean age was 56 years, and 62% were women. The prevalence of various comorbidities was higher among patients in the PND group, including digestive disorders (31% vs. 17% for comparison group), circulatory disorders (29% vs. 22%), and depression (4% vs. 3%) (all p < 0.01). Receipt of prescriptions for pain-related pharmacotherapy also was higher among PND patients, including nonsteroidal anti-inflammatory drugs (56% of PND patients had one or more such prescriptions vs. only 22% in the comparison group), opioids (49% vs. 12%), tricyclic antidepressants (20% vs. 1%), and antiepileptics (12% vs. 1%) (all p < 0.01). PND patients also averaged significantly more GP visits (22.8 vs. 14.2) and referrals to specialists (2.8 vs. 1.4) over one year (both comparisons p < 0.01). CONCLUSIONS: Patients with PNDs under the care of GPs in the UK have relatively high levels of use of healthcare services and pain-related pharmacotherapy.

Patterns of pharmacotherapy and health care utilization and costs prior to total hip or total knee replacement in patients with osteoarthritis.

OBJECTIVE: To examine patterns of pharmacotherapy and health care utilization and costs prior to total knee replacement (TKR) or total hip replacement (THR) in patients with osteoarthritis (OA). METHODS: Using a large US health insurance claims database, we identified all patients with OA who were ages ≥40 years and had undergone TKR or THR between January 1, 2006 and December 31, 2007. Patients with <2 years of complete data prior to TKR or THR were excluded, as were those with evidence of other conditions for which TKR or THR may be performed (e.g., rheumatoid arthritis). We then examined patterns of health care utilization and costs over the 2-year period preceding surgery. RESULTS: A total of 16,527 patients met all study entry criteria. Their mean ± SD age was 56.6 ± 6.1 years, and 56% of them were women. In the 2 years preceding surgery, 55% of patients received prescription nonsteroidal antiinflammatory drugs, 58% received opioids, and 50% received injections of corticosteroids. The numbers of patients receiving these drugs increased steadily during the presurgery period. The mean ± SD total health care costs in the 2 years preceding surgery were $19,466 ± 29,869, of which outpatient care, inpatient care, and pharmacotherapy represented 45%, 20%, and 20%, respectively. Costs increased from $2,094 in the eighth calendar quarter prior to surgery to $3,100 in the final quarter. CONCLUSION: Patients with OA who undergo THR or TKR have relatively high levels of use of pain-related pharmacotherapy and high total health care costs in the 2-year period preceding surgery. Levels of utilization and cost increase as the date of surgery approaches.

Impact of self-rated osteoarthritis severity in an employed population: cross-sectional analysis of data from the national health and wellness survey.

BACKGROUND: Although osteoarthritis (OA) often affects older persons, it has a profound effect on individuals actively employed. Despite reports of reduced productivity among workers with OA, data are limited regarding the impact of OA among workers. The objective of this study was to evaluate the impact of self-rated OA severity on quality of life, healthcare resource utilization, productivity and costs in an employed population relative to employed individuals without OA. METHODS: This cross-sectional analysis used data derived from the 2009 National Health and Wellness Survey (NHWS). Multivariable analyses characterized outcomes and costs (direct medical costs and indirect) among workers (full-time, part-time, or self-employed) ≥ 20 years of age who were diagnosed with OA and who self-rated their OA severity as mild, moderate, or severe relative to workers without OA. Evaluated outcomes included productivity, assessed using the Work Productivity and Impairment (WPAI) scale; health-related quality of life, using the SF-12v2 Health Survey; and healthcare resource utilization. RESULTS: 4,876 workers reported being diagnosed with OA (45.0% mild, 45.9% moderate, and 9.1% severe); 34,896 workers comprised the non-OA comparator cohort. There was a greater proportion of females in the OA cohort (55.5% vs 45.6%; P < 0.0001) and more individuals in the 40-64 year and ≥ 65 year age ranges (P < 0.0001). As OA severity increased, workers reported more frequent pain, poorer quality of life, greater use of specific healthcare resources (hospitalizations) and reduced productivity. All outcomes indicated a significantly greater burden among workers with OA relative to those without OA (P < 0.0001). Estimated total annual costs per worker were $9,801 for mild OA, $14,761 for moderate OA, $22,111 for severe OA compared with $7,901 for workers without OA (P < 0.0001). CONCLUSIONS: Workers with OA were characterized by significant disease and economic burdens relative to workers without OA that substantially increased with greater self-rated OA severity. Greater levels of OA severity were associated with reductions in quality of life and productivity, and increases in healthcare resource utilization and costs.

Resource utilization and costs before and after total joint arthroplasty.

BACKGROUND: The purpose of this study was to compare pre- and post-surgical healthcare costs in commercially insured total joint arthroplasty (TJA) patients with osteoarthritis (OA) in the United States (U.S.). METHODS: Using a large healthcare claims database, we identified patients over age 39 with hip or knee OA who underwent unilateral primary TJA (hip or knee) between 1/1/2006 and 9/30/2007. Utilization of healthcare services and costs were aggregated into three periods: 12 months "pre-surgery," 91 days "peri-operative," and 3 to 15 month "follow-up," Mean total pre-surgery costs were compared with follow-up costs using Wilcoxon signed-rank test. RESULTS: 14,912 patients met inclusion criteria for the study. The mean total number of outpatient visits declined from pre-surgery to follow-up (18.0 visits vs 17.1), while the percentage of patients hospitalized increased (from 7.5% to 9.8%) (both p < 0.01). Mean total costs during the follow-up period were 18% higher than during pre-surgery ($11,043 vs. $9,632, p < 0.01), largely due to an increase in the costs of inpatient care associated with hospital readmissions ($3,300 vs. $1,817, p < 0.01). Pharmacotherapy costs were similar for both periods ($2013 [follow-up] vs. $1922 [pre-surgery], p = 0.33); outpatient care costs were slightly lower in the follow-up period ($4338 vs. $4571, p < 0.01). Mean total costs for the peri-operative period were $36,553. CONCLUSIONS: Mean total utilization of outpatient healthcare services declined slightly in the first year following TJA (exclusive of the peri-operative period), while mean total healthcare costs increased during the same time period, largely due to increased costs associated with hospital readmissions. Further study is necessary to determine whether healthcare costs decrease in subsequent years.

Therapy switching, augmentation, and discontinuation in patients with osteoarthritis and chronic low back pain.

BACKGROUND: Recommended pain treatments for osteoarthritis (OA) and chronic low back pain (CLBP) are suboptimal, and limited information is available regarding patterns of pharmacotherapy among patients with these conditions. AIMS: Evaluate patterns of therapy switching, augmentation, and discontinuation after treatment initiation with select pain medications in patients with OA and CLBP. METHODS: Using the U.K. The Health Improvement Network (THIN) database, OA and CLBP patients newly prescribed (index-event) nonselective nonsteroidal anti-inflammatory drugs (NS-NSAIDs), cyclooxygenase-2 inhibitors (Cox-2s), acetaminophen, tramadol and weak or strong opioids were selected. Descriptive statistics, Kaplan-Meier analyses, and COX proportional hazards models were used to evaluate patterns of changes in pharmacotherapy during the 12-month postindex period. RESULTS: Rates of therapy switching, augmentation, and discontinuation, respectively, were significantly different (all P values<0.0001) across the evaluated medication cohorts for both OA and CLBP patients. Discontinuation rates in OA patients were 91.9% (NS-NSAIDs), 86.9% (Cox-2s), 91.4% (acetaminophen), 89.7% (tramadol), 93.2% (weak opioids), and 84.3% (strong opioids); and in CLBP patients were 97.2% (NS-NSAIDs), 94.0% (Cox-2s), 95.0% (acetaminophen), 92.8% (tramadol), 97.0% (weak opioids), and 86.8% (strong opioids). The rates of switching (range 30.0% to 59.6%) and augmentation (range 7.5% to 15.2%) were lower. Estimated probability evaluations suggested that two-thirds of patients who switched, augmented, or discontinued therapy did so within the first couple of months, and a majority did so within 6-months of treatment initiation. CONCLUSIONS: This study demonstrates that therapy switching and discontinuation of select pain medications were common among OA and CLBP patients in the U.K. and may result from inadequate pain relief or undesirable side effects.

Use and costs of prescription medications and alternative treatments in patients with osteoarthritis and chronic low back pain in community-based settings.

OBJECTIVE: To evaluate the use and direct medical costs of pharmacologic and alternative treatments for patients with osteoarthritis (OA) and chronic low back pain (CLBP). METHODS: The LifeLink™ Health Plan Claims Database was used to identify patients ≥18 years old, diagnosed with OA (N = 112,951) or CLBP (N = 101,294). Of these patients, 64,085 with OA and 47,386 with CLBP received pain-related treatments during CY2008 and were selected for inclusion. For patients in both cohorts, pharmacologic and alternative treatments, and direct medical costs were examined during CY2008. RESULTS: Opioids were the most frequently prescribed medication (>70%) in both groups, followed by nonselective nonsteroidal anti-inflammatory drugs (>50%). Over 30% received antidepressants, >20% received benzodiazepines, and 15% in each group received sedative hypnotics. Use of alternative treatments was as follows: chiropractor, OA 11%, CLBP 34%; physical therapy, 20% in both groups; transcutaneous electrical nerve stimulations (TENS), OA 14%, CLBP 22%; acupuncture, hydrotherapy, massage therapy, and biofeedback, <3% in both groups. Mean (SD) total healthcare costs among these patients were, OA: $15,638 ($22,595); CLBP: $11,829 ($20,035). Pharmacologic therapies accounted for approximately 20% of these costs, whereas alternative treatments accounted for only 3% to 4% of the total costs. CONCLUSIONS: Patients with OA and CLBP used a variety of pain-related and adjunctive medications. Although, alternative treatments are widely recommended, we found limited use of several of these in clinical practice, potentially due to the source of our data (commercial claims). Further research is needed to ascertain the extent to which such therapies contribute to the total costs of OA and CLBP management.

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.