Discovery of GSK251: A Highly Potent, Highly Selective, Orally Bioavailable Inhibitor of PI3Kδ with a Novel Binding Mode.

Optimization of a previously reported lead series of PI3Kδ inhibitors with a novel binding mode led to the identification of a clinical candidate compound 31 (GSK251). Removal of an embedded Ames-positive heteroaromatic amine by reversing a sulfonamide followed by locating an interaction with Trp760 led to a highly selective compound 9. Further optimization to avoid glutathione trapping, to enhance potency and selectivity, and to optimize an oral pharmacokinetic profile led to the discovery of compound 31 (GSK215) that had a low predicted daily dose (45 mg, b.i.d) and a rat toxicity profile suitable for further development.

Design and Development of a Macrocyclic Series Targeting Phosphoinositide 3-Kinase δ.

A macrocyclization approach has been explored on a series of benzoxazine phosphoinositide 3-kinase δ inhibitors, resulting in compounds with improved potency, permeability, and in vivo clearance while maintaining good solubility. The thermodynamics of binding was explored via surface plasmon resonance, and the binding of lead macrocycle 19 was found to be almost exclusively entropically driven compared with progenitor 18, which demonstrated both enthalpic and entropic contributions. The pharmacokinetics of macrocycle 19 was also explored in vivo, where it showed reduced clearance when compared with the progenitor 18. This work adds to the growing body of evidence that macrocyclization could provide an alternative and complementary approach to the design of small-molecule inhibitors, with the potential to deliver differentiated properties.

Optimization of Orally Bioavailable PI3Kδ Inhibitors and Identification of Vps34 as a Key Selectivity Target.

Optimization of a lead series of PI3Kδ inhibitors based on a dihydroisobenzofuran core led to the identification of potent, orally bioavailable compound 19. Selectivity profiling of compound 19 showed similar potency for class III PI3K, Vps34, and PI3Kδ, and compound 19 was not well-tolerated in a 7-day rat toxicity study. Structure-based design led to an improvement in selectivity for PI3Kδ over Vps34 and, a focus on oral phramacokinetics properties resulted in the discovery of compound 41, which showed improved toxicological outcomes at similar exposure levels to compound 19.

Translation of Inhaled Drug Optimization Strategies into Clinical Pharmacokinetics and Pharmacodynamics Using GSK2292767A, a Novel Inhaled Phosphoinositide 3-Kinase δ Inhibitor.

This study describes the pharmacokinetic (PK) and pharmaco-dynamic (PD) profile of N-(5-(4-(5-(((2R,6S)-2,6-dimethylmorpholino)methyl)oxazol-2-yl)-1H-indazol-6-yl)-2-methoxypyridin-3-yl)methanesulfonamide (GSK2292767A), a novel low-solubility inhaled phosphoinositide 3-kinase delta (PI3Kδ) inhibitor developed as an alternative to 2-(6-(1H-indol-4-yl)-1H-indazol-4-yl)-5-((4-isopropylpiperazin-1-yl)methyl)oxazole (nemiralisib), which is a highly soluble inhaled inhibitor of PI3Kδ with a lung profile consistent with once-daily dosing. GSK2292767A has a similar in vitro cellular profile to nemiralisib and reduces eosinophilia in a murine PD model by 63% (n = 5, P < 0.05). To explore whether a low-soluble compound results in effective PI3Kδ inhibition in humans, a first time in human study was conducted with GSK2292767A in healthy volunteers who smoke. GSK2292767A was generally well tolerated, with headache being the most common reported adverse event. PD changes in induced sputum were measured in combination with drug concentrations in plasma from single (0.05-2 mg, n = 37), and 14-day repeat (2 mg, n = 12) doses of GSK2292767A. Trough bronchoalveolar lavage (BAL) for PK was taken after 14 days of repeat dosing. GSK2292767A displayed a linear increase in plasma exposure with dose, with marginal accumulation after 14 days. Induced sputum showed a 27% (90% confidence interval 15%, 37%) reduction in phosphatidylinositol-trisphosphate (the product of phosphoinositide 3-kinase activation) 3 hours after a single dose. Reduction was not maintained 24 hours after single or repeat dosing. BAL analysis confirmed the presence of GSK2292767A in lung at 24 hours, consistent with the preclinical lung retention profile. Despite good lung retention, target engagement was only present at 3 hours. This exposure-response disconnect is an important observation for future inhaled drug design strategies considering low solubility to drive lung retention.

Discovery of 6-Amino-2-{[(1S)-1-methylbutyl]oxy}-9-[5-(1-piperidinyl)pentyl]-7,9-dihydro-8H-purin-8-one (GSK2245035), a Highly Potent and Selective Intranasal Toll-Like Receptor 7 Agonist for the Treatment of Asthma.

Induction of IFNα in the upper airways via activation of TLR7 represents a novel immunomodulatory approach to the treatment of allergic asthma. Exploration of 8-oxoadenine derivatives bearing saturated oxygen or nitrogen heterocycles in the N-9 substituent has revealed a remarkable selective enhancement in IFNα inducing potency in the nitrogen series. Further potency enhancement was achieved with the novel (S)-pentyloxy substitution at C-2 leading to the selection of GSK2245035 (32) as an intranasal development candidate. In human cell cultures, compound 32 resulted in suppression of Th2 cytokine responses to allergens, while in vivo intranasal administration at very low doses led to local upregulation of TLR7-mediated cytokines (IP-10). Target engagement was confirmed in humans following single intranasal doses of 32 of ≥20 ng, and reproducible pharmacological response was demonstrated following repeat intranasal dosing at weekly intervals.

Improving workplace productivity--it isn't just about reducing absence.

Employers must get more aggressive in their health and productivity strategies. A comprehensive strategy includes data analytics across health and lost-time programs, absence policies that meet today's needs for both employer and employee, health and wellness programs targeting modifiable health behaviors, and absence program administration that is aligned to operational goals. This article targets key aspects of a comprehensive long-term health and productivity strategic vision. An organization can use these aspects independently to address immediate tactical issues while it develops its broader strategy. The target areas include a view from the perspective of data management, absence program design and management, employee health and wellness, and behavioral health.

Economic burden of epilepsy among the privately insured in the US.

BACKGROUND: The direct cost burden of epilepsy in the US from a third-party payer perspective has not been evaluated. Furthermore, no study has quantified the indirect (work-loss) cost burden of epilepsy from an employer perspective in the US. OBJECTIVE: To assess the annual direct costs for privately insured US patients diagnosed with epilepsy, and indirect costs for a subset of employees from an employer perspective. METHODS: A retrospective analysis of a claims database for the privately insured, including employee disability claims from 1999 through 2005 and comprising 17 US companies, was conducted. A total of 4323 patients aged 16-64 years (including 1886 employees) with at least one epilepsy diagnosis (International Classification of Diseases, 9th edition, Clinical Modification [ICD-9-CM] code 345.x) over the period 1999-2004 were included. The control group was a demographically matched cohort of randomly chosen beneficiaries without an epilepsy diagnosis. All had continuous health coverage during 2004 (baseline) and 2005 (study period). Main outcome measures included annual direct (medical and pharmaceutical) costs and, for employees, indirect (disability and medically related absenteeism) and total costs for the study period. Wilcoxon rank-sum tests were used for univariate comparisons of annual direct costs, indirect costs (costs for the subset of employees with these data), and total (direct and indirect) costs during the study period. Two-part multivariate models that adjusted for patient characteristics were also used to compare costs between the study and control groups. RESULTS: Patients with epilepsy were an average age of 43 years and 57% were female. They had more co-morbidities than controls. On average, direct annual costs were significantly higher per patient with epilepsy than per control ($US10 258 vs $US3862, respectively; p < 0.0001) [year 2005 values], with an annual per-patient difference of $US6396. Epilepsy-related costs ($US2057) accounted for 20% of direct costs for patients with epilepsy. Annual indirect costs were significantly higher for employees with epilepsy than for employed controls ($US3192 vs $US1242, respectively; p < 0.0001), with a difference of $US1950. Total direct plus indirect costs for employees with epilepsy were also higher than those for employed controls ($US13 595 vs $US5338, respectively; p < 0.0001), with a difference of $US8257. CONCLUSIONS: Epilepsy was associated with significant economic burden. The excess direct costs in patients with epilepsy are underestimated when only epilepsy-related costs are considered.

Direct and indirect costs associated with epileptic partial onset seizures among the privately insured in the United States.

PURPOSE: Compare annual direct and indirect costs between privately insured U.S. patients with epileptic partial onset seizures (POS) and matched controls. METHODS: One thousand eight hundred fifty-nine patients (including a subset of 758 employees) with >or=1 (POS) diagnosis (ICD-9-CM: 345.4.x-345.7.x), 1999-2004, ages 16-64 years, were identified from a privately insured claims database. Control group was an age- and gender-matched cohort of randomly chosen beneficiaries without epilepsy (ICD-9-CM: 345.x). All were required to have continuous health coverage during 2004 (baseline) and 2005 (study period). Chi-square tests were used to compare baseline comorbidities. Univariate and multivariate analyses were used for comparisons of annual direct (medical and pharmaceutical) and indirect costs during the study period. RESULTS: Patients with POS were on average 42 years of age, and 57% were women. Patients with POS had significantly higher rates of mental health disorders, migraine, and other neurologic disorders, and higher Charlson comorbidity index (CCI) compared with controls. On average, direct annual costs were significantly higher for POS patients ($11,276) compared with controls ($4,087), p < 0.001; difference of $7,190. Epilepsy-related costs (i.e., costs for antiepileptic drugs, claims with epilepsy or convulsions diagnoses) accounted for $3,290 (29% of direct costs). Employees with POS had substantial and significantly higher indirect (disability- and medically related absenteeism) costs compared with controls ($3,431 vs. $1,511, p < 0.001). Multivariate analyses supported the matched-control univariate findings. CONCLUSION: Patients with POS had significantly higher costs compared with matched controls. Epilepsy-related costs underestimate the excess costs of patients with partial onset seizures.

Comparison of health care use and costs in newly diagnosed and established patients with fibromyalgia.

UNLABELLED: In 2004, the American Pain Society (APS) issued evidence-based fibromyalgia treatment recommendations. The objective of this claims database analysis is to describe prescription and medical use in patients with newly diagnosed and established fibromyalgia. Privately insured patients with 2+ myalgia/myositis claims (1999 to 2005) were categorized as newly diagnosed or established; this dichotomy involves comparisons between prediagnosis (S1) and postdiagnosis (S2) stages in the newly diagnosed and between newly diagnosed (S2) and established patients (S3). Use of APS guideline medications increased across stages: selective serotonin reuptake inhibitors (SSRIs) (S1, S2, S3: 20.6%, 22.9%, 25.3%), serotonin norepinephrine reuptake inhibitors (SNRIs) (4.5%, 6.4%, 8.9%), pregabalin/gabapentin (5.4%, 7.4%, 8.8%), benzodiazepines (19.0%, 21.1%, 24.2%), non-benzodiazepine sedatives (9.1%, 11.5%, 13.7%) (all P < .0001), and opioids (39.5%, 43.3%, 43.9%; S1 vs S2, P < .0001; S2 vs S3, P = .2835). Use of multiple therapeutic classes also increased across stages: 3+ classes (7.1%, 9.6%, 11.8%) (all P < .0001). Office visits to providers increased, on average, after diagnosis: primary care (70.9%, 78.3%, 76.3%; all P < .0001), chiropractors (28.8%, 51.1%, 53.3%; all P < .0001), rheumatologists (4.2%, 9.9%, 10.5%; S1 vs S2, P < .0001; S2 vs S3, P = .0595), mental health (6.4%, 7.3%, 8.3%; S1 vs S2, P < .0001, S2 vs S3, P = .0003). Average health care costs rose after diagnosis in the newly diagnosed group (S1: $6555 vs S2: $8654, P < .0001). PERSPECTIVE: This paper investigates prescription drug and medical care use with respect to stages of fibromyalgia diagnosis. Established fibromyalgia patients use more medical resources and have higher rates of concomitant medication use than newly diagnosed fibromyalgia patients. Findings can help educate providers regarding optimal drug treatment patterns in this population.

The use of partially porous particle columns for the routine, generic analysis of biological samples for pharmacokinetic studies in drug discovery by reversed-phase ultra-high performance liquid chromatography-tandem mass spectrometry.

Recent years have seen the introduction of new high performance liquid chromatography (HPLC) instruments and columns that are capable of achieving high resolution, high speed liquid chromatographic separations at back pressures up to 1000 bar, so-called ultra-high performance liquid chromatography (UHPLC). Ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) is gaining widespread use for this purpose, and for this approach to be successful a generically applicable, robust column is required. Here, data are presented showing the robustness of a partially porous 2.7 microm diameter particle material in this application and the accuracy and precision of an assay for a typical pharmaceutical in plasma. This stationary phase material is evaluated for performance and compared with other materials frequently used for similar analyses using a test mix currently used routinely in our laboratories to assess the performance of UHPLC-MS/MS systems. The partially porous material demonstrates similar resolving power to sub-2 microm materials under the ballistic gradient chromatography conditions employed and exhibits excellent resilience over the analysis of thousands of protein precipitated plasma extracts. It is suggested that this stationary phase material can be an invaluable tool in generic, high throughput assays for pharmaceutical bioanalysts.

Comparative and interactive effects of depression relative to other health problems on work performance in the workforce of a large employer.

OBJECTIVES: To present data on the comparative and interactive workplace costs of depression relative to other health problems in the workforce of a large employer. METHODS: The World Health Organization Health and Work Performance Questionnaire was used to assess self-reported health problems and work performance. Survey data were linked to medical-pharmacy claims data. Regression analysis was used to assess comparative effects of depression in the absence and presence of comorbidities on Health and Work Performance Questionnaire measures of work performance. RESULTS: Depression had the largest individual-level effect on work performance of any condition examined. Several comorbid conditions exacerbated the effect of depression, but had no effects in the absence of depression. CONCLUSIONS: Depression is a strong predictor of decrements in work performance. Other conditions that often co-occur with depression, including anxiety and fatigue-sleep disturbance, exacerbate the adverse effect of depression.

The economic impact of pre-dialysis epoetin alpha on health care and work loss costs in chronic kidney disease: an employer's perspective.

The objective of the study was to quantify the direct and indirect incremental costs of epoetin alpha (EPO) therapy for anemia in pre-dialysis chronic kidney disease (CKD). Using employer claims data from January 1998 to January 2005, direct (medical and pharmacy) and indirect (sick leave and disability) costs were compared between CKD-anemic patients treated with EPO before dialysis (n = 199) and those not treated with an erythropoiesis-stimulating therapy (EST) (n = 196). Among the results, incremental direct and indirect cost savings for EPO-treated patients were $1443 and $328 per member per month (PMPM) (p < 0.001), respectively, compared to non-EST-treated patients with anemia. After multivariate adjustments, direct and indirect costs remained significantly lower by $852 and $308 PMPM (p < 0.001), respectively, for the EPO-treated group. Direct costs during the first 6 months of dialysis also were significantly lower for the EPO-treated group (who received EPO before dialysis), by $1515 PMPM (p = 0.0267, in multivariate regression). In conclusion, anemic CKD patients treated with EPO before dialysis had significantly lower direct and indirect costs compared to non-EST-treated patients.

Employees with fibromyalgia: medical comorbidity, healthcare costs, and work loss.

OBJECTIVES: To compare 2005 health care resources among matched samples of employees with fibromyalgia (FM), osteoarthritis (OA), and controls. METHODS: Using a claims database of privately insured individuals, FM and OA samples were derived from those with two or more disease-specific claims in 1999 to 2005 (> or =1 in 2002 to 2005). RESULTS: Total costs for employees with FM ($10,199) approached OA costs ($10,861, P = 0.3758) and were significantly higher than controls ($5274, P < 0.0001). Cost components varied across disease-specific samples (direct medical: FM $7286 vs OA $8325, P < 0.0287; pharmacy: FM $1630 vs OA $1341; indirect: FM $2913 vs OA $2537, P < 0.0001). Employees with FM had more claims than OA for psychiatric diagnoses, chronic fatigue, and most pain conditions. Use of multiple prescription drug classes was common in both samples. CONCLUSIONS: FM imposes significant economic burden. Work loss contributes substantially to the impact.

The impact of psoriasis on health care costs and patient work loss.

BACKGROUND: There are few comprehensive estimates of the cost of psoriasis in the United States. OBJECTIVE: We sought to quantify the incremental direct medical and indirect work loss costs associated with psoriasis. METHODS: A de-identified claims database from 31 self-insured employers during the period 1998 to 2005 was used. Patients with at least two psoriasis diagnosis claims (N = 12,280) were compared with 3 control subjects (matched on year of birth and sex) without psoriasis. Multivariate two-part regression analysis was used to isolate the incremental cost of psoriasis by controlling for comorbidities and other confounding factors. RESULTS: After multivariate adjustment, the incremental direct and indirect costs of psoriasis were approximately $900 and $600 (P < .001) per patient per year, respectively. LIMITATIONS: The database used in this study does not contain information on patient out-of-pocket costs or loss of productivity costs at work. CONCLUSION: The incremental cost of psoriasis is approximately $1500 per patient per year, with work loss costs accounting for 40% of the cost burden.

The direct and indirect cost burden of atopic dermatitis: an employer-payer perspective.

The goal of this study was to quantify the incremental direct medical and indirect work-loss costs associated with patients diagnosed with atopic dermatitis (AD). A de-identified administrative claims database was used comprising 5.1 million covered beneficiaries from 31 Fortune 500 self-insured employers between 1998 and 2005. Patients with at least two AD diagnosis claims (N = 13,749) were compared with three matched controls (based on yr of birth and gender) with no AD diagnosis (N = 41,247). In addition, a multivariate two-part regression analysis was used to isolate the cost increase attributable to AD by controlling for confounding factors such as age, gender, health plan type, comorbidities, organ transplantation, industry of employer, region, and year. Direct medical and indirect work-loss costs for the AD group were higher on average by $88 and $64 per patient per month, respectively (both P< .001). After multivariate adjustment, the total incremental cost per patient per month for the AD group was $83 (direct: $52, P< .001; indirect: $31, P< .001). Employer-payers experience a significant annual cost burden of $991 per patient attributable to AD. Employee disability and increased sick days account for 38% of the cost burden.

Risk of cancer treatment-associated bone loss and fractures among women with breast cancer receiving aromatase inhibitors.

BACKGROUND: Aromatase inhibitors (AIs) are a novel hormonal therapy for patients with breast cancer. However, AIs can cause bone loss by blocking estrogen production. This study aims to assess the association between AIs and treatment-related bone loss in a large managed-care population of women with breast cancer. PATIENTS AND METHODS: With use of medical and pharmacy claims, data from > 5 million beneficiaries between January 1, 1998, and January 31, 2005, we identified 12,368 patients with > or = 2 breast cancer claims in a 6-month period who also had no bone metastases and no previous osteoporosis or fracture claims. Patients who had received antiestrogen (eg, tamoxifen) therapy were also excluded. One thousand three hundred fifty-four patients receiving an AI (anastrozole, exemestane, or letrozole) were compared with 11,014 controls who did not receive an AI with respect to their risk of bone loss. The observation start date for the AI and control groups was defined as the service date of the first AI claim and breast cancer claim, respectively. The endpoints include (1) bone loss, consisting of osteoporosis or osteopenia, and (2) clinical fractures. RESULTS: The univariate analysis found that the prevalence of bone loss was 8.7% in the AI group versus 7.1% in the control group, resulting in a significant relative risk of 1.3 (95% confidence interval [CI], 1.1-1.6; P = 0.01). The prevalence of bone fracture was also significantly increased in the AI group compared with the controls (13.5% vs. 10.3%) with a relative risk of 1.4 (95% CI, 1.2-1.6, P = 0.001). Multivariate Cox proportional hazards regressions showed that after adjusting for age and comorbidities, the risk of bone loss remained significantly higher in the AI group than in the non-AI group, with a 27% (95% CI, 4%-55%; P = 0.02) and 21% (95% CI, 3%-43%; P = 0.02) increase in the risk of bone loss and fractures, respectively. CONCLUSION: This retrospective longitudinal analysis of a large cohort of patients with breast cancer corroborates previous findings from smaller clinical trials and demonstrates that AI therapies carry an increased risk of bone loss. Monitoring and treatment management strategies to reduce bone loss risk are warranted in women receiving an AI for breast cancer.

A retrospective claims database analysis to assess patterns of interstitial cystitis diagnosis.

OBJECTIVE: Interstitial cystitis (IC) is often misdiagnosed as one of several other conditions manifesting similar symptoms. This analysis assesses the potential extent of IC misdiagnosis while considering concomitant conditions in a managed care population and identifies predictors of IC diagnosis. RESEARCH DESIGN AND METHODS: Administrative insurance claims data covering 1.7 million lives (1999-2003) were analyzed. Insurance enrollees with >or= 1 IC diagnosis (ICD-9-CM of 595.1x) were identified as IC patients. A random sample of non-IC controls was selected using a 10:1 matching ratio. Six-month incidence rates of 'commonly misdiagnosed conditions', (overactive bladder, urinary tract infection, chronic pelvic pain, endometriosis, prostatitis) were compared before and after patients' initial IC diagnosis and the reduction in incidence rate of commonly misdiagnosed conditions was used as a suggestive measure of the extent of IC misdiagnosis. The Kaplan-Meier method was used to assess the extent that commonly misdiagnosed conditions were predictors of subsequent IC. A Cox Proportional Hazards regression model (that adjusts for patient demographics, concomitant and misdiagnosed conditions) was used to estimate the hazard ratio (HR) of these conditions. Similar analyses were performed for the 'commonly concomitant conditions' (fibromyalgia, irritable bowel syndrome, vulvodynia). RESULTS: There were 992 IC patients and 9920 controls identified. The reduced incidence of commonly misdiagnosed conditions after initial IC diagnosis suggests that the misdiagnosis rate could be as high as 38% within the 6-month period before initial IC diagnosis. CONCLUSIONS: Diagnoses of commonly misdiagnosed conditions are significant predictors of future IC diagnosis. When overlooked, potential misdiagnosis of IC can lead to underestimation of the true prevalence of IC. Similarly, diagnoses of commonly concomitant conditions are significant predictors of future IC diagnosis. These initial findings based on claims data suggest hypotheses for further investigation with clinical data. These results suggest more consideration of IC as a diagnosis is warranted, especially when certain diagnoses are repeatedly made and the resulting treatments do not alleviate the patient's symptoms.

Interstitial Cystitis: Cost, treatment and co-morbidities in an employed population.

INTRODUCTION: Recent literature indicates that interstitial cystitis (IC) may affect 20% of women and a smaller proportion of men, although many individuals with IC may be misdiagnosed or remain undiagnosed. Factors that can contribute to the cost of IC include medical and drug utilisation related to treatment and diagnosis of IC and associated conditions (e.g. depression), as well as employee work loss. This study assesses the direct medical cost and indirect cost of work loss for IC patients in the first year after diagnosis, and evaluates IC treatment patterns and prevalence of co-morbidities. METHODS: Data for patients under the age of 65 years with at least one diagnosis of IC (n = 749) were drawn from a de-identified, administrative database of approximately 2 million beneficiaries that included medical, drug and disability claims for 1999-2002. A 2 : 1 matched control sample of patients without an IC diagnosis (non-IC sample) was randomly selected based on patient characteristics. Indirect costs were calculated from a subgroup of 152 IC patients (plus their matched controls) who had disability information available. Costs incurred in the first year after IC diagnosis and co-morbidities were compared between IC patients and the non-IC sample, with the difference in costs defined as 'excess costs' of IC patients. Treatment patterns were profiled in the 2 months following initial diagnosis of IC. Descriptive statistics are presented. A multivariate two-part model was applied to estimate the IC direct medical cost, indirect cost and total cost to adjust for observed patient demographics and co-morbidities. Statistical significance was evaluated by the bootstrap method. RESULTS: The average IC patient had 130% higher direct costs (p < 0.05) and the average IC employee patient had 84% higher indirect costs than the average non-IC control individual. IC patients also had a higher diagnostic prevalence of prostatitis (relative risk [RR] = 40.0), endometriosis (RR = 7.4), vulvodynia (RR = 6.9), chronic pelvic pain (RR = 5.8) and urinary tract infections (RR = 5.1) [all p < 0.05]. IC patients were also more likely to report depression (RR = 2.8) and anxiety (RR = 4.5 ) than non-IC controls (all p < 0.05). Seventeen percent of IC patients received pentosan polysulfate therapy, the only US FDA-approved oral drug therapy indicated for treating IC, within the first 2 months after diagnosis. Of these patients, 69% received at least one 'other' drug from the non-approved oral medications studied. Approximately one-third of IC patients received only 'other' drug therapies, and almost half of IC patients received no drug treatment within the first 2 months after the initial diagnosis. CONCLUSIONS: IC is a costly disease associated with co-morbidities. Following diagnosis, patients with IC are commonly untreated or treated with non-approved drug therapies. It is possible that more accurate diagnosis and earlier and more appropriate treatment of IC would lead to better management (or even prevention) of co-morbidities and reduce healthcare costs, and this should be investigated in future studies.

Economic burden of illness for employees with painful conditions.

OBJECTIVE: We sought to compare the medical services utilization and average annual direct (ie, medical and medication) and indirect (ie, work-loss) costs for employees with painful conditions to a random sample ("average employee"). METHODS: An employer administrative claims database (approximately 600,000 insured lives) was used to identify patients with ICD-9 codes for painful conditions. Direct costs were total employer medical and medication costs and indirect costs were associated with medically related absenteeism days and disability claims. RESULTS: Among employees with painful conditions, total costs were 1.5 to 3.5 times as high (P < 0.01) as those of the average employee (ie, 7088 US dollars to 16,874 US dollars compared with 4,849 US dollars) depending on the painful condition. CONCLUSIONS: Painful conditions are costly to employers, and better management/treatment of such conditions may help reduce the associated employer economic burden.

Employees with overactive bladder: work loss burden.

OBJECTIVE: This study assessed the indirect work loss costs to employers as the result of employees with overactive bladder (OAB). METHODS: Study samples were drawn from an administrative database of 1.2 million beneficiaries, including medical and disability claims (1999-2002). OAB employees were compared with matched employees without OAB. RESULTS: OAB was associated with higher annual occurrences of work loss (P < 0.01). Employees with OAB had 2.2 excess work loss days as the result of medically related absenteeism and 3.4 excess days as the result of disability compared with employees without OAB (P < 0.01 for both comparisons). Employees with OAB had increased risk of disability (P < 0.01), and female employees with OAB had a higher risk of disability than male employees (P < 0.01). CONCLUSIONS: This study found that OAB was associated with work loss costs to employers resulting from increased number of employee sick days and increased risk of employee disability.