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Cost-effectiveness evaluations play an important role in recommendations for use of pediatric vaccines that are set forth by the US Advisory Committee on Immunization Practices (ACIP). The fact that these evaluations are undertaken and accorded weight suggests that a critical value for designating pediatric vaccines as cost-effective (or not) must exist. For recommended pediatric vaccines, however, reported incremental cost-effectiveness ratios (ICERs) have varied greatly, and there does not appear to be an explicit threshold used by the ACIP to define how much is too much to pay for the prevention of communicable diseases in children. Further complicating this issue is the fact that conventional ICER thresholds-expressed in terms of cost per quality-adjusted life-year (QALY) gained-accord value only to length and quality of life and may not reflect our preferences as individuals or a society. For example, risk, an important attribute of many healthcare decisions, is ignored by the QALY model, as is the distribution of health benefits across different members of society. Are we indeed indifferent about risk and do we really believe that the value of disease prevention in children should be measured by the same "yardstick" as that for older adults? Accordingly, do we really believe that "a QALY is a QALY"? These issues, which are reviewed and discussed in this article, are more than just of theoretical interest; the answers impact how public health policy is determined, which impacts the lives and well-being of entire populations as well as the budgets of payers.

Aims To compare the safety and efficacy of insulin glargine 300 U/mL (Gla-300) versus first-generation standard-of-care basal insulin analogues (SOC-BI; insulin glargine 100 U/mL or insulin detemir) at 6 months. Methods In the 12-month, open-label, multicentre, randomized, pragmatic ACHIEVE Control trial, insulin-naive adults with type 2 diabetes (T2D) and glycated haemoglobin A1c (HbA1c) 64-97 mmol/mol (8.0%-11.0%) after ≥1 year of treatment with ≥2 diabetes medications were randomized to Gla-300 or SOC-BI. The composite primary endpoint, evaluated at 6 months, was the proportion of participants achieving individualized HbA1c targets per HEDIS criteria without documented symptomatic (blood glucose ≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia at any time of the day at 6 months. Results Of 1651 and 1653 participants randomized to Gla-300 and SOC-BI, respectively, 31.3% and 27.9% achieved the composite primary endpoint at 6 months (odds ratio [OR] 1.19; 95% CI 1.01-1.39; P = 0.03 for superiority); 78.4% and 75.3% had no documented symptomatic or severe hypoglycaemia (OR 1.19; 95% CI 1.01-1.41). Changes from baseline to month 6 in HbA1c, fasting plasma glucose, weight, and BI analogue dose were similar between groups. Conclusions Among insulin-naive adults with poorly controlled T2D, Gla-300 was associated with a statistically significant higher proportion of participants achieving individualized HEDIS HbA1c targets without documented symptomatic or severe hypoglycaemia (versus SOC-BI) in a real-life population managed in a usual-care setting. The ACHIEVE Control study results add value to treatment decisions and options for patients, healthcare providers, payers, and decision makers. ClinicalTrials.gov identifier: NCT02451137 This article is protected by copyright. All rights reserved.

Background: Chronic idiopathic constipation (CIC) is a common gastrointestinal disorder in community settings. Limited information exists on its treatment with the prosecretory agents linaclotide and lubiprostone. This retrospective cohort study investigated real-world pharmacotherapy patterns of linaclotide and lubiprostone. Methods: Patients (≥18 years) with CIC who received linaclotide or lubiprostone between January 2013 and December 2015 were identified in a United States health insurance claims database. Follow-up was from the date of the earliest claim for either drug to the end of continuous enrolment or switch to the alternative agent. Patterns of pharmacotherapy, evidence of irritable bowel syndrome (IBS), and concomitant use of selective serotonin reuptake inhibitors were examined using the International Classification of Diseases, Ninth or Tenth Revision, Clinical Modification codes and National Drug Codes. Results: In total, 43,164 and 17,743 patients with CIC received linaclotide and lubiprostone, respectively (~80% women, mean age ~47 years). Approximately 40% of subjects (linaclotide: 40.1%; lubiprostone: 37.6%) had evidence of IBS. Over a mean follow-up of 17 months, mean (standard deviation) treatment duration in patients without IBS was 6.6 (7.9) months for linaclotide and 4.5 (6.5) months for lubiprostone. Treatment episodes >180 days were more common with linaclotide (36.1%) than with lubiprostone (23.2%). At 12 months, Kaplan–Meier estimates of switching from lubiprostone to linaclotide and from linaclotide to lubiprostone were 13.4 and 5.6%, respectively. The number of patients receiving serotonin reuptake inhibitors was unchanged with treatment (~22%). Conclusions: Most patients with CIC receive linaclotide or lubiprostone for 1 year. Additional research is warranted to understand the potential reason(s) for early discontinuation.

At least one-half of adults beginning an immunization series with a three-dose hepatitis B virus (HBV) vaccine (ENGERIX-B, RECOMBIVAX-B) have been reported not to receive the third dose. Use of a two-dose vaccine may improve adherence and lead to greater overall levels of seroprotection.To examine expected levels of adherence and overall seroprotection at one year among adults in routine clinical settings beginning an immunization series with either ENGERIX-B or the two-dose HBV vaccine, HEPLISAV-B.Decision-analytic model comparing expected levels of adherence and overall seroprotection at one year among a hypothetical cohort of one million previously unvaccinated adults aged ≥ 30 years receiving first doses of either ENGERIX-B or HEPLISAV-B in a routine clinical setting. We stratified the population by age (30-49 years vs ≥ 50 years) to allow for possible differences in adherence and seroprotection. We estimated our model using published adherence rates for HBV vaccines, and reported seroprotection rates by number of doses administered. We also compared total expected costs of HBV immunization with each vaccine.Use of a two-dose rather than three-dose HBV vaccine would increase the expected number of adults seroprotected at one year by 275,000 per one million persons beginning immunization series, largely reflecting a gain of 290,000 in the expected number of persons fully vaccinated. Results were similar for the two age groups. While the cost per dose of HEPLISAV-B exceeds that of ENGERIX-B, its estimated mean cost per person seroprotected at one year is $50-$70 (∼15%) lower.Use of a two-dose HBV vaccine would increase the number of adults fully seroprotected at one year compared with the number expected with a three-dose vaccine. Notwithstanding its higher unit cost, mean expected cost per person seroprotected is substantially lower for HEPLISAV-B than ENGERIX-B as a result of much higher levels of seroprotection.

Background: Pulmonary arterial hypertension (PAH) is a disease characterized by dyspnea, fatigue, chest pain and syncope. As there is no known cure for PAH, the goal of treatment is to control symptoms and slow disease progression. Sildenafil, a phosphodiesterase-5 inhibitor, has been indicated to improve exercise capacity in PAH in both the United States and the European Union since 2005; since 2009, it also has been indicated in the United States to delay clinical worsening. Patterns of sildenafil use in PAH patients have not been reported. Objectives: To describe patterns of treatment with sildenafil among commercially insured patients in the United States with PAH. Methods: Using a large U.S. healthcare claims database, we identified all patients with evidence of PAH (International Classification of Disease, 9th Revision, Clinical Modification [ICD-9-CM] diagnosis codes 416.0, 416.8) and receipt of sildenafil between January 1, 2005 and September 30, 2008. The date of each patient’s earliest pharmacy claim for sildenafil was designated as his or her “index date”; patients with

ObjectiveThis was a post hoc analysis of the Edaravone Phase III Study MCI186-19 (‘Study 19’) to examine the utility of clinical staging systems as end points in clinical trials in amyotrophic lateral sclerosis (ALS).MethodsAmyotrophic Lateral Sclerosis Functional Rating Scale—Revised item scores from Study 19 were retrospectively mapped to King’s stage and Milano-Torino staging (MiToS) stage. We assessed the percentage of patients who experienced progression in King’s and MiToS stages during Study 19. We also assessed disease progression in subgroups of patients according to baseline King’s stage.ResultsDuring double-blind treatment, the percentage of patients who experienced a progression in King’s stage was lower for edaravone (42.0%, 95% CI 30.4% to 53.6%) than placebo (55.9%, 95% CI 44.1% to 67.6%). The most pronounced effect was noted among patients who were in stage 1 and was maintained throughout open-label treatment. An analysis of a ≥2-stage progression in MiToS stage showed no difference between treatment arms during double-blind treatment, but during the open-label period, more rapid progression was noted among patients in the placebo–edaravone arm than among those in the edaravone–edaravone arm (log-rank test, pConclusionsThe King’s and MiToS staging systems provided utility in assessing clinical progression in Edaravone Study 19. These findings may support the use of staging systems as end points in ALS clinical trials and to understand the timing of benefit as measured by these scales.

Patients with idiopathic pulmonary fibrosis and emphysema may have artificially preserved lung volumes.In this post hoc analysis, we investigated the relationship between baseline emphysema and fibrosis extents, as well as pulmonary function changes, over 48 weeks.Data were pooled from two phase III, randomized, double-blind, placebo-controlled trials of IFN-γ-1b in idiopathic pulmonary fibrosis (GIPF-001 [NCT00047645] and GIPF-007 [NCT00075998]). Patients with Week 48 data, baseline high-resolution computed tomographic images, and FEVEmphysema was identified in 38% of patients. A negative correlation was observed between fibrosis and emphysema extents (r = -0.232; P 0.001). In quartile analysis, patients with the greatest emphysema extent (28 to 65%) showed the smallest FVC decline, with a difference of 3.32% at Week 48 versus patients with no emphysema (P = 0.047). In multivariate analyses, emphysema extent greater than or equal to 15% was associated with significantly reduced FVC decline over 48 weeks versus no emphysema or emphysema less than 15%. No such association was observed for diffusing capacity of the lung for carbon monoxide or composite physiologic index.FVC measurements may not be appropriate for monitoring disease progression in patients with idiopathic pulmonary fibrosis and emphysema extent greater than or equal to 15%.

BACKGROUND The lifetime economic burden of thoracic spinal cord injury (SCI) is known to be high, but evidence of variability of costs in relation to the American Spinal Injury Association Impairment Scale (AIS) grade is limited. OBJECTIVE To estimate lifetime economic costs of hospitalization by AIS grade in thoracic SCI. METHODS Using SCI Model Systems data from January 2000 to March 2016 from the National Spinal Cord Injury Statistical Center, we estimated mean total annual days of all-cause hospitalization by AIS grade among persons with thoracic SCI, based on assessments 1, 5, and 10 yr post-injury. We combined this information with secondary cost data and projections of life expectancy to estimate lifetime economic costs of hospitalization by AIS grade in persons aged 35 yr at time of thoracic SCI. Future costs were discounted to present value at 3% annually. RESULTS One year post-injury, mean total annual days of hospitalization ranged from 2.1 for persons with AIS-D injuries to 5.9 for those who were AIS-A. Similar differences were noted 5 and 10 yr post-SCI. The estimated net present value of expected lifetime costs of hospitalization following thoracic SCI at age 35 yr was $321 534, $249 514, $188 989, and $68 120 (2015 US$) for AIS-A, AIS-B, AIS-C, and AIS-D injuries, respectively. CONCLUSION Persons with less severe thoracic SCI, as reflected in AIS grade, spend fewer days in hospital over their lifetimes, leading to lower costs of inpatient care. Therapies improving AIS grade following thoracic SCI may provide cost savings in addition to addressing substantial unmet need.

Purpose The purpose of this study was to estimate the risk and economic burden of peristomal skin complications (PSCs) in a large integrated healthcare system in the Midwestern United States. Design Retrospective cohort study. Subjects and setting The sample comprised 128 patients; 40% (n = 51) underwent colostomy, 50% (n = 64) underwent ileostomy, and 10% (n = 13) underwent urostomy. Their average age was 60.6 ± 15.6 years at the time of ostomy surgery. Methods Using administrative data, we retrospectively identified all patients who underwent colostomy, ileostomy, or urostomy between January 1, 2008, and November 30, 2012. Trained medical abstractors then reviewed the clinical records of these persons to identify those with evidence of PSC within 90 days of ostomy surgery. We then examined levels of healthcare utilization and costs over a 120-day period, beginning with date of surgery, for patients with and without PSC, respectively. Our analyses were principally descriptive in nature. Results The study cohort comprised 128 patients who underwent ostomy surgery (colostomy, n = 51 [40%]; ileostomy, n = 64 [50%]; urostomy, n = 13 [10%]). Approximately one-third (36.7%) had evidence of a PSC in the 90-day period following surgery (urinary diversion, 7.7%; colostomy, 35.3%; ileostomy, 43.8%). The average time from surgery to PSC was 23.7 ± 20.5 days (mean ± SD). Patients with PSC had index admissions that averaged 21.5 days versus 13.9 days for those without these complications. Corresponding rates of hospital readmission within the 120-day period following surgery were 47% versus 33%, respectively. Total healthcare costs over 120 days were almost $80,000 higher for patients with PSCs. Conclusions Approximately one-third of ostomy patients over a 5-year study period had evidence of PSCs within 90 days of surgery. Costs of care were substantially higher for patients with these complications.

Summary Using data from the Study of Osteoporotic Fractures (SOF), several clinical characteristics predictive of near-term (1-year) risk of hip and non-vertebral fracture among elderly osteoporotic women were identified, and a subset of those for hip fracture was incorporated into a risk assessment tool. Additional research is needed to validate study findings. Introduction While several risk factors are known to contribute to long-term fracture risk in women with osteoporosis, factors predicting fracture risk over a shorter time horizon, such as over a 1-year period, are less well-established. Methods We utilized a repeated-observations design and data from the Study of Osteoporotic Fractures to identify factors contributing to near-term risk of hip fracture and any non-vertebral fracture, respectively, among osteoporotic women aged ≥65 years. Potential predictors of hip fracture and any non-vertebral fracture over the 1-year period subsequent to each qualifying SOF exam were examined using multivariable frailty models. Because the discriminative ability of the hip fracture model was acceptable, a corresponding risk-prediction tool was also developed. Results Study population included 2499 women with osteoporosis, who contributed 6811 observations. Incidence of fracture in the 1-year period subsequent to each exam was 2.2% for hip fracture and 6.6% for any non-vertebral fracture. Independent predictors of hip fracture included low total hip T-score, prior fracture, and risk factors for falls (multivariable model c-statistic = 0.71 (95% CI 0.67–0.76)). Independent predictors of any non-vertebral fracture included age, total hip T-score, prior falls, prior fracture, walking speed, Parkinson’s disease or stroke, and smoking (multivariable model c-statistic = 0.62 (0.59–0.65)). Conclusions Several clinical characteristics predictive of hip and non-vertebral fracture within a 1-year follow-up period among elderly women with osteoporosis were identified, and a subset of those for hip fracture was incorporated into a risk assessment tool. Assessment of these risk factors may help guide osteoporosis treatment choices by identifying patients in whom there is urgency to treat. Additional research is needed to validate the findings of this study and the accuracy of the risk assessment tool. Electronic supplementary material The online version of this article (doi:10.1007/s00198-017-4103-3) contains supplementary material, which is available to authorized users.

Introduction: In an analysis of pooled data from the GIPF-001 (NCT00047645) and GIPF-007 (NCT00075998) trials of patients with IPF, emphysema extent ≥15% was associated with reduced forced vital capacity (FVC) decline vs no emphysema/emphysema Methods: 455 patients from GIPF-001 and GIPF-007 were stratified by baseline emphysema extent. Parameters collected included FVC, forced expiratory volume in 1 second (FEV 1 ), carbon monoxide diffusing capacity (DLco), University of California San Diego Shortness of Breath Questionnaire (UCSD-SOBQ) score and composite physiologic index (CPI). Results: Baseline parameters for patients stratified by emphysema extent are reported in the Table. Compared with patients with emphysema >0% to 1 /FVC (p 1 , DLco, FVC/DLco, UCSD-SOBQ or CPI. Conclusions: The results of this post-hoc analysis demonstrate differences in baseline characteristics in patients with IPF and emphysema ≥15% vs >0% to

Although clinical guidelines for management of community-acquired pneumonia (CAP) in non-intensive care unit ("non-ICU") hospitalized patients have changed substantially over the last decade, it is unknown how treatment of this disease has evolved over this period.Using data from100 U.S. hospitals, we identified all adults (aged ≥18 years) hospitalized for CAP between January 1, 2000, and June 30, 2009 ("study period"). We excluded patients admitted to ICU24 hours of admission, those not starting antibiotics24 hours of admission, those not receiving antibiotics for ≥48 hours (if alive), and those with probable healthcare-associated pneumonia. We defined "initial therapy" as all parenteral antibiotics received ≤24 hours of admission, and we examined changes in such therapy over the study period. The statistical significance of changes in initial therapy was ascertained using 2-tailed χ tests.We identified 40,392 patients who met all selection criteria. In 2000, the most frequently used initial regimens were levofloxacin (24.0% of all such admissions), ceftriaxone (9.0%), cefotaxime (7.3%), ceftriaxone plus levofloxacin (3.2%) and azithromycin plus cefotaxime (3.0%); in 2009, they were ceftriaxone plus azithromycin (18.5%), levofloxacin (12.7%), ceftriaxone (6.6%), moxifloxacin (4.7%) and ceftriaxone + levofloxacin (3.2%). Use of single-agent regimens declined between 2000 and 2009 (from 48.2%-30.0%); use of vancomycin almost doubled (13.1%-23.3%). All findings were statistically significant (P0.01).Initial antibiotic therapy for non-ICU CAP has changed substantially in the United States over the past decade, in line with evidence of widespread antibiotic resistance, evolving treatment guidelines and, most recently, quality improvement initiatives that tie hospital payments to guideline-based care.

The percentage of isolates resistant to essential antibiotics among clinically significant bacterial pathogens was evaluated using data from 80089 qualifying admissions in 19 US hospitals (2007-2010). Percentage resistant was highest for the following pathogen/antibiotic pairs: Enterococcus faecium/vancomycin (87.1% [95% CI 86.0-88.1] of 4024 isolates), Staphylococcus aureus/oxacillin-methicillin (56.8% [56.1-57.4] of 23477 isolates), S. aureus/clindamycin (39.7% [39.1-40.4] of 21133 isolates), Pseudomonas aeruginosa/fluoroquinolones (32.6% [31.8-33.5] of 10982 isolates), and Escherichia coli/fluoroquinolones (31.3% [30.8-31.8] of 30715 isolates). The percentage resistant was 3.9% (3.2-4.9) for E. faecium/daptomycin (n = 2029 isolates). While these results are consistent with those from earlier studies in many respects, the percentage of E. faecium isolates resistant to daptomycin, while still small, is higher than has been reported to date.

The results of a study to estimate the economic costs of venous thromboembolism (VTE) in hospitalized nonsurgical patients during initial admissions and subsequent to hospital discharge are presented.Using a database linking admission records from more than 150 U.S. hospitals to health insurance claims, 49,948 patients 40 years of age or older who were hospitalized at least once during a 6-year period for diagnoses other than VTE or traumatic injury and who met other inclusion criteria were identified. Costs were tallied from the index admission to postdischarge day 180 for patients with and patients without evidence of VTE. Ordinary least-squares regression was used to estimate the independent relationship between VTE and total health care costs, controlling for differences in patient characteristics.Two hundred forty-two patients (0.5%) had VTE during the index admission, 317 (0.6%) had VTE after the index admission discharge; in total, 559 (1.1%) had VTE through postdischarge day 180. Among the 242 patients with VTE during their index admission, the adjusted mean total health care costs over 180 days were $17,848 higher than among those without VTE ($47,416 versus $29,568, p0.001); for the 317 patients with postdischarge VTE, the adjusted mean total 180-day costs were $51,863 higher than for those without postdischarge VTE ($74,136 versus $22,273, p0.001).Among medically ill patients admitted to the hospital, health care costs were significantly higher among those who developed VTE during hospitalization or after discharge compared with those who did not develop VTE.

To document the risk of skeletal complications in patients with bone metastases from breast cancer (BC), lung cancer (LC), or prostate cancer (PC) in routine clinical practice. We used data from two large US health systems to identify patients aged ≥18 years with primary BC, LC, or PC and newly diagnosed bone metastases between January 1, 1995 and December 31, 2009. Beginning with the date of diagnosis of bone metastasis, we estimated the cumulative incidence of skeletal-related events (SREs) (spinal cord compression, pathologic fracture, radiation to bone, bone surgery), based on review of medical records, accounting for death as a competing risk. We identified a total of 621 BC, 477 LC, and 721 PC patients with newly diagnosed bone metastases. SREs were present at diagnosis of bone metastasis in 22.4, 22.4, and 10.0 % of BC, LC, and PC patients, respectively. Relatively few LC or PC patients received intravenous bisphosphonates (14.8 and 20.2 %, respectively); use was higher in patients with BC, however (55.8 %). In BC, cumulative incidence of SREs during follow-up was 38.7 % at 6 months, 45.4 % at 12 months, and 54.2 % at 24 months; in LC, it was 41.0, 45.4, and 47.7 %; and in PC, it was 21.5, 30.4, and 41.9 %. More than one half of patients with bone metastases had evidence of SREs (BC: 62.6 %; LC: 58.7 %; PC: 51.7 %), either at diagnosis of bone metastases or subsequently. SREs are a frequent complication in patients with solid tumors and bone metastases, and are much more common than previously recognized in women with BC.

Objective: This study aims to compare the effectiveness of insulin glargine 300 U/mL (Gla-300) with its accompanying patient support program with that of other basal insulin and available patient support programs in patients with type 2 diabetes (T2D) in a real-world setting in terms of achieving HEDIS (Healthcare Effectiveness Data and Information Set) individualized glycemic targets without documented symptomatic hypoglycemia. Methods: Achieve Control is a US-based, multicenter, randomized, open-label, active-controlled, parallel group pragmatic Phase IV trial in insulin-naïve patients with T2D uncontrolled on ≥2 oral antidiabetes drugs (OAD) and/or glucagon-like peptide-1 receptor antagonists (GLP-1 RA). Inclusion criteria include a diagnosis of T2D, age ≥18 years, and glycated hemoglobin (HbA1c) between 8.0% and 11.0%. Patients will be assigned to either the Gla-300 or other basal insulin group. The primary end point is the proportion of patients achieving HEDIS HbA1c targets (Conclusion: Pragmatic clinical trials offer the potential to assess comparative effectiveness in broadly based patient populations receiving care (with or without a corresponding educational support program) in real-world clinical settings. The results of Achieve Control should elucidate the benefits of management of T2D with Gla-300 versus other basal insulins in terms of patient outcomes, experiences, and perceptions, and its impact on healthcare resource utilization and cost. Clinical trial registration: www.clinicaltrials.gov identifier is NCT02451137.

Background: Analysis of data from the GIPF-007 trial of IFNγ-1b suggested that FVC decline may be confounded by the extent of emphysema (EE) on HRCT in patients with IPF. IPF progression may, therefore, not be captured using FVC. This finding was further investigated in a combined analysis of data from the GIPF-007 trial and another IFNγ-1b trial, GIPF-001. Methods: The study sample included 455 patients from GIPF-001 and -007. EE and extent of fibrosis were assessed on HRCT. The relationship between EE (no emphysema/EE 1 and DLco at baseline. Results: 281 patients (61.8%) did not have evidence of emphysema on HRCT. Among 174 patients with evidence of emphysema, 56 (12.3%) had EE ≥15% and 118 (25.9%) had EE Conclusion: Patients with IPF and EE ≥15% had, on average, less decline in FVC over 48 weeks than those with no emphysema or EE

Objective: To characterize adherence with antidepressants, antiepileptic drugs, and beta blockers as prophylaxis against migraine in typical clinical practice. Methods: Using a large US health insurance claims database (calendar years 2003 to 2005), we identified all patients with migraine who began prophylaxis with selected antidepressants, antiepileptic drugs, or beta blockers (“study agents”). Patients not continuously enrolled for 6 months prior to start of prophylaxis (“pretreatment”) and for 6 months subsequently (“follow-up”) were excluded. Treatment cohorts were constituted based on the type of prophylaxis received. Adherence with migraine prophylaxis was examined by type of agent received using medication possession ratios (MPRs), defined as total days with medication divided by total follow-up days. MPR

Objectives To examine patterns of health care utilization and costs in patients with generalized anxiety disorder (GAD) who begin treatment with benzodiazepine anxiolytics as add-on therapy. Study Design In a large US health insurance database, we identified all patients with evidence of GAD (International Classification of Diseases, 9th Revision, Clinical Modification diagnosis code 300.02) who received ≥90 days of therapy with a selective serotonin reuptake inhibitor or venlafaxine between January 1, 2003 and December 31, 2007. Among these patients, we selected those who initiated a course of benzodiazepine add-on therapy. Designating the date of initial receipt of a benzodiazepine as the “index date,” we examined health care utilization and costs over the 6-month period preceding this date (“pre-index”) and the 12-month period following it (“follow-up”). Results A total of 2131 patients met all study inclusion criteria. Patients averaged 32 days of therapy with benzodiazepines (median [interquartile range] = 20 [10-30]); 13% of patients received >90 days of therapy, however. In general, levels of health care utilization during the first 6 months of follow-up were higher than those during the pre-index period; between months 7 and 12 of follow-up, however, they were somewhat lower than pre-index levels. Mean (SD) total health care costs were $5148 ($10,658), $6325 ($15,741), and $5373 ($11,230) during pre-index, months 1-6 of follow-up, and months 7-12 of follow-up, respectively. Conclusions Levels of health care utilization and costs increase following initiation of add-on therapy with a benzodiazepine in patients with GAD receiving selective serotonin reuptake inhibitors or venlafaxine. Although duration of add-on therapy is typically brief, some patients are treated for >90 days, raising potential concerns about risks of dependency and sedation.

Objective.Patients with rheumatoid arthritis (RA) are at increased risk of death. Modern RA therapy has been shown to improve health status, but the relationship of such improvements to mortality risk is unknown. We assessed the relationship between health status and all-cause mortality in patients with RA, using the Health Assessment Questionnaire (HAQ) and the Medical Outcomes Study Short Form-36 questionnaire (SF-36) physical and mental component summary scores (PCS, MCS).Methods.Subjects (n = 10,319) were selected from the National Data Bank for Rheumatic Diseases, a prospective longitudinal observational US study with semiannual assessments of HAQ, PCS, and MCS. Risk of death up to 7 years through 2006 was obtained from the US National Death Index. Relationship of HAQ, PCS, and MCS to mortality was assessed using Cox regression models; prediction accuracy was compared using Harrell’s concordance coefficient (C).Results.Over 64,888 patient-years of followup, there were 1317 deaths. Poorer baseline health status was associated with greater mortality risk. Adjusting for age, sex, and baseline PCS and MCS, declines in PCS and HAQ were associated with higher risk of death. HAQ improvement was associated with reduced mortality risk from 6 months through 3 years; a similar relationship was not observed for PCS or MCS improvement. Controlling for baseline values, change in PCS or HAQ did not improve prediction accuracy.Conclusion.The HAQ and the SF-36 PCS are similarly and strongly associated with mortality risk in patients with RA. Change in these measures over time does not appear to add to predictive accuracy over baseline levels.

Objective: To conduct a systematic review of available data from reports of randomized controlled trials on the efficacy, safety, and tolerability of drugs used to treat postherpetic neuralgia (PHN), a common type of neuropathic pain. Data Sources: The MEDLINE (1950-June 30. 2009) and EMBASE (1974-June 30, 2009) databases were used to identify source studies, in conjunction with a review of reference citations from identified published reports. Study Selection and Data Extraction: We selected all English-language reports of randomized placebo-controlled trials of the efficacy, tolerability, and safety of drugs (oral or transdermal) used for treatment in patients with PHN. Studies with treatment duration less than 4 weeks were excluded. From each identified trial, we extracted information on (1) placebo-corrected percentage reductions in pain intensity from randomization to end of active treatment; (2) relative risks of withdrawal due to lack of efficacy; (3) relative risks of various adverse events; and (4) relative risks of withdrawal due to adverse events. Data Synthesis: Twelve reports of randomized controlled trials in patients with PHN were identified, involving 8 different agents (amitriptyline, capsaicin, divalproex sodium, gabapentin, morphine, nortriptyline, pregabalin, tramadol). Most studies were small, involving fewer than 200 patients. Pain intensity was reported to have been reduced significantly with all drugs (range: 13.8% [tramadol] to 42,4% [amitriptyline]); data were pooled using techniques of meta-analysis when information was available from more than 1 trial. No clinical trial reported a significant reduction in risk of withdrawal as a result of lack of efficacy. Analysis of adverse events was greatly limited by erratic and inconsistent reporting and wide variation in sample sizes. Conclusions: While available literature establishes the efficacy of 6 drugs in treatment of PHN, it does not provide adequate guidance as to which agents are best to treat this condition, in part because of inadequate reporting of data on tolerability and safety.

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

Objectives Although the economic costs of substance misuse have been extensively examined in the published literature, information on the costs of nonmedical use of prescription opioids is much more limited, despite being a significant and rapidly growing problem in the United States. Methods We estimated the current economic burden of nonmedical use of prescription opioids in the United States in terms of direct substance abuse treatment, medical complications, productivity loss, and criminal justice. We distributed our broad cost estimates among the various drugs of misuse, including prescription opioids, down to the individual drug level. Results In 2006, the estimated total cost in the United States of nonmedical use of prescription opioids was $53.4 billion, of which $42 billion (79%) was attributable to lost productivity, $8.2 billion (15%) to criminal justice costs, $2.2 billion (4%) to drug abuse treatment, and $944 million to medical complications (2%). Five drugs--OxyContin, oxycodone, hydrocodone, propoxyphene, and methadone--accounted for two-thirds of the total economic burden. Discussion The economic cost of nonmedical use of prescription opioids in the United States totals more than $50 billion annually; lost productivity and crime account for the vast majority (94%) of these costs.

BACKGROUND: While the clinical and economic consequences of S. aureus pneumonia in healthcare settings have been well documented, much less is known about community-acquired S. aureus pneumonia (CAP). METHODS: We retrospectively identified all patients admitted to a large US urban teaching hospital between January 2005 and May 2008 with pneumonia and positive blood or respiratory cultures for S. aureus within 48 hours of admission. Patients with suspected healthcare-associated pneumonia (HCAP) were excluded from the study sample, using established criteria (eg, recent hospitalization, admission from nursing home, hemodialysis). Patients were designated as having methicillin-resistant (MRSA) or methicillin-susceptible (MSSA) CAP based on initial S. aureus isolates. Initial therapy was designated “appropriate” vs. “inappropriate” based on expected susceptibility of the organism to the regimen received. RESULTS: We identified a total of 128 CAP patients with S. aureus isolates; mean (standard deviation [SD]) age was 60 (17) years. A total of 55 patients (43%) had initial cultures positive for MRSA. Patients with MRSA CAP were more likely to receive inappropriate initial therapy (24 [44%] vs. 13 [18%] for MSSA; P = 0.002). Approximately 25% of all patients underwent surgery for pneumonia, 69% received mechanical ventilation, 79% were admitted to intensive care unit (ICU), and 24% died in hospital. Mean (SD) length of stay was 17.0 (15.7) days, and total hospital charges averaged $127,922 ($154,605) per patient; there were no significant differences between patients with MRSA vs. MSSA CAP. CONCLUSION: Outcomes are poor, hospital stays are long, and costs of care are high in patients with S. aureus CAP, and do not differ between those with MRSA vs. MSSA. Journal of Hospital Medicine 2010. © 2010 Society of Hospital Medicine.

Objective: The aim of this analysis was to assess alternative methods of identification of patients treated with peritoneal dialysis (PD) in health care claims databases for possible use in future analyses of costs of this treatment modality. Methods: Using a US health insurance claims database spanning January 1, 2004, to December 31, 2006, we identified all patients with renal failure who satisfied a case-finding algorithm for PD anticipated to be highly specific, but not necessarily sensitive—namely, ≥2 claims for PD-related physician services (algorithm 1). All claims from these patients were assessed to identify additional PD-related codes, from which 6 additional algorithms were developed, each of which focused on specific categories of billing codes (eg, diagnostic, procedural/service, equipment). Patient selection was then reimplemented using these alternative algorithms. Concordance between the various algorithms and the extent to which resulting samples were similar in terms of patient characteristics, health care resource utilization, and costs were assessed. Results: We identified a total of 132,274 patients in the database with ≥1 claim for renal failure and valid enrollment data. Among these patients, a total of 2329 satisfied case-selection criteria for algorithm 1, and 4031 patients met criteria for at least 1 of the 7 algorithms for PD. The most sensitive algorithm identified 2859 patients who might have received PD; the least sensitive, 211. Concordance between algorithms was relatively poor. Patients identified using each algorithm were similar, however, with respect to mean age (45–50 years), sex (54%–56% male), and the prevalence of selected comorbidities. Annualized median health care costs were similar across the various algorithms (range, US $80,967-$118,668). Conclusions: Based on the results from this analysis, it seems that health care providers bill insurers for PD-related care using a variety of codes. Investigators using health insurance claims data for analyses of patients treated with PD need to take this into account.

In a meta-analysis of data from randomized trials, the risk of febrile neutropenia during myelosuppressive chemotherapy was reported to be lower with pegfilgrastim prophylaxis than filgrastim prophylaxis. However, there is limited information on the comparative effectiveness of these agents in clinical practice.This study was undertaken to compare the risks of hospitalization for neutropenic complications of chemotherapy in US clinical practice in patients with primary solid tumors receiving pegfilgrastim or filgrastim prophylaxis.This was a retrospective cohort study employing a US health insurance database. The source population included all patients who received chemotherapy for a primary solid tumor between January 2003 and December 2005 and who received filgrastim or pegfilgrastim during their first course of chemotherapy. All unique chemotherapy cycles were identified for each patient, and cycles in which pegfilgrastim or filgrastim was administered by cycle day 5 (considered to represent prophylaxis) were selected and pooled for analysis. The risks of hospitalization for neutro-penic complications (using both narrow and broad criteria) and for any reason were then compared between cycles in which filgrastim or pegfilgrastim prophylaxis was administered. Generalized estimating equations were used to control for potential confounding variables.Filgrastim prophylaxis was used in 1193 unique chemotherapy cycles (mean [SD] number of days per cycle, 4.5 [3.3]); for pegfilgrastim prophylaxis, the number of unique chemotherapy cycles was 14,570. First-cycle use represented 16% of all cycles analyzed. The mean ages of patients receiving filgrastim and pegfilgrastim prophylaxis were 61 and 60 years, respectively. Breast cancer was the most common tumor type (52% and 51%), followed by non-Hodgkin's lymphoma (21% and 18%) and lung cancer (11% and 15%). Hospitalization for neutropenic complications (narrow criterion) occurred during 2.1% of filgrastim cycles and 1.2% of pegfilgrastim cycles; hospitalization for neutropenic complications (broad criterion) occurred in a respective 4.8% and 3.1% of cycles; and hospitalization for all causes occurred in 8.7% and 6.3% of cycles (all, P0.01). The risks of hospitalization were consistently lower for chemotherapy cycles that involved pegfilgrastim prophylaxis compared with filgrastim prophylaxis (odds ratios = 0.64-0.73; P0.05).The risk of hospitalization for neutro-penic complications during cancer chemotherapy in clinical practice was approximately one third higher among patients who received filgrastim prophylaxis than among those who received pegfilgrastim prophylaxis.

article i nfo Background: Osteoporosis is a major cause of morbidity and mortality. Clinical trials have shown the effectiveness of bisphosphonates, the most commonly prescribed treatments, in reducing fracture risk. The population-based effectiveness of bisphosphonates in clinical practice is uncertain. Methods: This retrospective cohort study used a matched design that compared time to clinical fracture in at- risk community women who initiated a bisphosphonate medication between 7/1/1996 and 6/30/2006 to those who did not. The study was conducted in an HMO in Oregon and Washington. Clinical electronic databases provided data. Eligible members were newly treated women aged ≥55 years with either a BMD T- score of ≤−2.0 or a prior qualifying clinical fracture. They did not have contraindications for bisphosphonate therapy or a diagnosis associated with secondary osteoporosis (n=1829). They were matched to a similar comparison group (n=1829; total N=3658). The primary outcome was the first new incident fracture validated through chart review (closed clinical fracture of any bone except face, skull, finger, or toe or pathological fracture secondary to malignancy) during follow-up. An intention-to-treat analysis used Cox proportional hazards models to estimate the hazard ratio of fracture for treated relative to comparison patients, adjusting for differences in potential confounders. Results: Treated and comparison patients were similar in mean age (72.0 years) and history of fracture (about 45%). The treated group had more women with T-scores of ≤−2.5 (67.3% vs. 54.7%) and a lower mean weight (146.6 lb vs. 151.8 lb). Only about 45% of treated patients had a bisphosphonate medication possession ratio (MPR) of ≥0.80. During follow-up, 198 (10.8%) of patients in the treated group had incident fractures, vs. 179 (9.8%) of patients in the comparison group. After adjustments, patients in the treated group were 0.91 (95% CI 0.74-1.13) as likely to have an incident fracture as the comparison patients (p=0.388). The treatment effect remained non-significant after accounting for MPR. Conclusions: In this analysis of a community cohort of post-menopausal women at risk, the fracture risk of patients who received bisphosphonates did not differ significantly from those who did not. An enhanced understanding of this lack of treatment effect is urgently needed.

Purpose: To examine the use of pregabalin in patients with painful neuropathic disorders under the care of general practitioners (GPs) in the U.K. Materials and Methods: Using a large U.K. database of GP encounters, we identified all persons aged ≥ 18 years with at least one GP encounter with a diagnosis of a painful neuropathic disorder (eg, postherpetic neuralgia, diabetic peripheral neuropathy) between January 1, 2004 and July 31, 2006. Among these patients, we then identified those who initiated therapy with pregabalin; the date of initial receipt of pregabalin was designated the “index date.” We then examined use of pregabalin over the 6-month period following this date (“follow-up”), as well as changes in the use of other pain-related medications (eg, opioids, tricyclic antidepressants [TCAs], other antiepileptics [AEDs]) between the 6-month period preceding the index date (“pretreatment”) and follow-up. Patients with less than 6 months of pretreatment and follow-up data were excluded, as were those without any encounters during pretreatment for a painful neuropathic disorder. Results: A total of 1,400 patients (1.4% of all identified patients with painful neuropathic disorders) initiated therapy with pregabalin and met all other entry criteria; mean age was 62 years, and 58% were women. During pretreatment, most (54%) patients received three or more different types of pain-related medications. During follow-up, patients averaged four prescriptions for pregabalin, totaling 93 therapy days. Compared with pretreatment, fewer patients received other pain-related medications during follow-up, including TCAs (37% during pretreatment vs. 27% during follow-up), opioids (64% vs. 55%), and AEDs other than pregabalin (36% vs. 16%) (all P

Background Several systematic reviews of randomized controlled trials (RCTs) of drugs to treat neuropathic pain have reported summary estimates of efficacy – specifically, the number needed to treat (NNT). Aims To examine whether summary NNTs for drugs to treat neuropathic pain provide useful guidance for clinical decision making. Methods We examined the methods used to pool data across RCTs in systematic reviews – in particular, the extent of heterogeneity of agents (and dosages), neuropathic pain syndromes, and outcome measures. Results Published summary estimates of NNTs of drugs to treat neuropathic pain embody substantial heterogeneity, in that they reflect a pooling of data across agents with different mechanisms of action, across patients with different neuropathic pain syndromes, and/or across different outcome measures. Conclusions Summary NNT estimates may have limited clinical relevance, due to problems of heterogeneity. The most that can be extracted from systematic reviews published to date is the identity of drugs that have demonstrated efficacy for specific types of neuropathic pain, and the strength of such evidence.

To examine characteristics and patterns of healthcare utilization of patients with fibromyalgia (FM) under the care of general practitioners (GPs) in Germany.Retrospective cohort study, using a large electronic database with information on GP encounters in Germany (IMS MediPlus). We identified all patients, agedor =18 years, with any encounters for FM (ICD-10 diagnosis code M79.7) between February 1, 2004 and January 31, 2007. We also constituted a comparison group consisting of randomly selected patients with one or more GP encounters - but none for FM - during this period, who we matched to FM patients based on age and sex. Characteristics and healthcare utilization of patients in the FM and comparison groups were then examined over the 1-year period, February 1, 2006-January 31, 2007.Prevalence of co-morbidities; use of pain-related pharmacotherapy; number of GP office visits; number of specialist referrals; and number of sick notes (physician-excused absences from work).The study sample consisted of 4983 FM patients and an identical number in the comparison group. Mean age was 58 years; 87% were women. The prevalence of various co-morbidities was greater among FM patients, including painful neuropathies (33% vs. 18% for comparison group) and depression (20% vs. 5%) (both p0.01); more FM patients also received pain-related pharmacotherapy (67% vs. 28%; p0.01). Compared with patients in the comparison group, FM patients averaged approximately twice as many GP visits (11.4 [SD=10.1] vs. 5.8 [7.5]), referrals (4.5 [5.2] vs. 2.2 [3.6]), and sick notes (0.6 [1.8] vs. 0.3 [1.1]) (all p0.01).Information in the study database is limited to GP encounters, and the sensitivity and specificity of our case-finding methods are unknown.Patients with FM under the care of GPs in Germany have comparatively more co-morbidities and higher levels of healthcare utilization.

Initial antibiotic therapy in hospitalized adults with complicated intra-abdominal infection (cIAI) usually is empiric. We explored the economic consequences of failure of such therapy in this patient population.Using a large U.S. multi-institutional database, we identified all hospitalized adults admitted between April 1, 2003, and March 31, 2004; who had any cIAI; underwent laparotomy, laparoscopy, or percutaneous drainage of an intra-abdominal abscess ("surgery"); and received intravenous (IV) antibiotics. Initial therapy was characterized in terms of all IV antibiotics received, on the day of or one day before initial surgery. Antibiotic failure was designated on the basis of the need for reoperation or receipt of other IV antibiotics postoperatively. Switches to narrower spectrum agents and changes in regimen prior to discharge with no other evidence of clinical failure were not counted as antibiotic failures. Using multivariable linear regression, duration of IV antibiotic therapy, hospital length of stay, and total inpatient charges were compared between patients who did and did not fail initial therapy. Mortality was compared using multivariable logistic regression.Among 6,056 patients who met the study entrance criteria, 22.4% failed initial antibiotic therapy. Patients who failed received an additional 5.6 days of IV antibiotic therapy (10.4 total days [95% confidence interval 10.1, 10.8] days vs. 4.8 total days [4.8, 4.9] for those not failing), were hospitalized an additional 4.6 days (11.6 total days [11.3, 11.9] vs. 6.9 total days [6.8, 7.0], respectively), and incurred $6,368 in additional inpatient charges ($16,520 [$16,131, $16,919] vs. $10,152 [$10,027, $10,280]) (all, p0.01). They also were more likely to die in the hospital (9.5% vs. 1.3%; multivariable odds ratio 3.58 [95% confidence interval 2.53, 5.06]).Failure of initial IV antibiotic therapy in hospitalized adults with cIAIs is associated with longer hospitalization, higher hospital charges, and a higher mortality rate.

Background Cost of neutropenic complications of myelosuppressive chemotherapy has been reported to be substantial. Prior research, however, has focused on initial hospitalization only and has failed to account for follow-on care. Patients and methods Using a US health-care claims database, all adult cancer patients who received a course of chemotherapy were identified. For each such patient, each unique cycle of chemotherapy within the course and each occurrence of neutropenic complications within these cycles were characterized. Patients developing neutropenic complications in a given cycle (neutropenia patients), starting with the first, were matched (1 : 1) to those who did not develop neutropenic complications in that cycle (comparison patients), and health-care costs (i.e. expenditures) were tallied for each matched pair. Results Neutropenia patients (n = 373) and comparison patients were similar in terms of baseline characteristics. Costs of neutropenia-related care were $12 397 (95% confidence interval $10 274–$14 754) higher for neutropenia versus comparison patients [$14 407 ($12 357–$16 743) versus $2010 ($1490–$2553)]. Among neutropenia patients, mean cost of initial hospitalization for neutropenic complications was $7813 ($6537–$9379); cost of all subsequent neutropenia-related care averaged $6594 ($5217–$8272). Conclusions Neutropenic complications of myelosuppressive chemotherapy are costly. Prior research focusing on initial hospitalization only may have underestimated the cost of these complications by as much as 40%.

Patients with cancer may receive erythropoiesis-stimulating agents (ESAs), including darbepoetin alfa (DA) or epoetin alfa (EA), to treat cancer-related anemia (CRA). DA and EA differ, however, with respect to their assumed duration of effect and thus their approved frequency of dosing, complicating direct comparison of their doses and costs.The objective of this study was to examine, from the perspective of a third-party payer, patterns of use and costs of DA and EA in patients with CRA, using episode-based methodology to account for differences in assumed duration of effect and frequency of dosing with these products.Using a large US health insurance claims database, we identified all patients with cancer who received ESAs between January 1, 2005, and June 30, 2005 (study period). For each such patient, we identified all unique episodes of care (EOCs) with DA or EA, and then compared mean weekly dose and cost of ESA therapy within these EOCs, which were calculated using the ratio of total dose received and total cost of ESA therapy, respectively, to total EOC duration; only the first EOC for each patient was considered. EOCs were assumed to begin on the date of first ESA administration within the study period, and end on the date of final ESA administration (within the episode) plus an assumed duration of effect based on the ESA received and corresponding dose. We also estimated the ratio of mean weekly dose of EA (in units) to mean weekly dose of DA (in micrograms) (EA/DA weekly dose ratio). Multivariate regression was used to control for differences in baseline characteristics of EA and DA patients.We identified a total of 1226 patients with complete EOCs with ESAs (EA, 381; DA, 845). DA patients were more likely to have had evidence of receipt of chemotherapy (54% vs 47% for EA; P = 0.02); they also had more comorbidities (mean Charlson comorbidity scores, 4.3 and 3.9, respectively; P0.01). Estimated mean (95% CI) weekly dose within EOCs was 97 microg (94-99) for DA, and 43,184 U (40,181-46,589) for EA; EA/DA weekly dose ratio was 445:1. Adjustment for differences in patient characteristics yielded a slightly lower ratio (403:1). Results were sensitive to the exclusion of EOCs consisting of a single administration of ESA therapy and/or the addition of an assumed duration of effect to the final ESA dose administered.Cost comparisons of DA and EA are sensitive to the assumed duration of effect added to the final dose of ESA therapy, especially for EOCs with relatively few administrations.

Objective To assess cost-effectiveness of abatacept in patients with moderately to severely active RA and inadequate response to MTX. Methods We developed a simulation model to depict progression of disability [in terms of the HAQ Disability Index (HAQ-DI)] in women aged 55-64 yrs with moderately to severely active RA and inadequate response to MTX. At model entry, patients were assumed to receive either only MTX or MTX plus abatacept. Patients were then tracked from model entry until death. Future health-state utilities and medical-care costs (except study therapy) were estimated based on predicted values of the HAQ-DI. The model was estimated using data from a Phase III clinical trial of abatacept plus various secondary sources. Cost-effectiveness was expressed in terms of incremental cost (2006 US$) per quality-adjusted life-year (QALY) gained over alternatively 10 yrs and a lifetime. Costs and health effects were both discounted at 3% annually. Results Over 10 yrs, abatacept would yield 1.2 additional QALYs (undiscounted) per patient (4.6 vs 3.4 for MTX) at an incremental (discounted) cost of $51,426 ($103,601 vs $52,175, respectively); over a lifetime, corresponding figures were 2.0 QALYS (6.8 vs 4.8) and $67,757 ($147,853 vs $80,096). Cost-effectiveness was [mean (95% CI)] $47,910 ($44,641, $52,136) per QALY gained over 10 yrs and $43,041 ($39,070, $46,725) per QALY gained over a lifetime. Findings were robust in sensitivity analyses. Conclusion Abatacept is cost-effective by current standards of medical practice in patients with moderately to severely active RA and inadequate response to MTX.

Summary Purpose: To examine the characteristics and healthcare costs of fibromyalgia syndrome (FMS) patients in clinical practice.

In the Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial, the risk of new-onset diabetes was reported to be 23% lower among patients initiating therapy with valsartan versus amlodipine. The objective of our study was to examine whether this finding is generalizable to 'real-world' clinical practice. A retrospective cohort design and a large US health insurance database were employed for analyses. Study subjects included all hypertensive patients, aged >or=35 years, who were free from diabetes and who initiated treatment with valsartan (n=9999) or amlodipine (n=18 698) between January 1999 and March 2005. Unadjusted absolute risks of diabetes were 21.4 (95% confidence interval (CI) 18.9-24.3) and 26.3 (95% CI 24.3-28.3) per 1000 patient-years for valsartan and amlodipine, respectively; the corresponding relative risk (RR) for valsartan was 0.82 (95% CI 0.70-0.94). Multivariate analyses - controlling for age, sex, presence of hypercholesterolemia, cardiovascular disease and kidney disease, and pretreatment medical care expenditures - yielded similar results (RR=0.79, 95% CI 0.68-0.92). Our study thus corroborates the finding from VALUE that diabetes risk is lower for patients who receive valsartan versus amlodipine, and extends this finding to a 'real-world' setting.

We developed a decision-analytic model to examine the economic impact of shifting the locus of care for patients with painful neuropathies from specialists to GPs. The impetus for such a shift was assumed to be a formal education program, focusing on the recognition and treatment of neuropathic pain, conducted for GPs. In the model, all patients with neuropathic pain were assumed to initiate care with their GPs and then be referred to specialists and, ultimately, pain clinics as required for adequate pain control. Two alternative scenarios were examined--the "current" arrangement in which most patients were assumed to be referred for treatment by specialists and pain clinics and a "hypothetical" arrangement in which GPs were assumed to play an expanded role in the treatment of neuropathic pain and which, therefore, often precluded the need for referral. The model was populated with clinical, epidemiologic, and economic data from Norway. A total of 34,951 persons in Norway were estimated to seek care for painful neuropathies each year. The formal education program was assumed to cost 1.5 million Kroner (NOK). Shifting the locus of care from specialists to GPs would result in 4,715 additional GP visits, but 12,123 fewer specialist visits and 7,967 fewer visits to pain clinics. This change would result in estimated savings to the Norwegian health-care system in 2004 of 74.1 million NOK (approx. US $11.9 million). A partial shift in the locus of care of painful neuropathies from specialists to GPs may result in substantial cost savings to the Norwegian health-care system.

Background: Concurrent emphysema may be associated with spurious preservation of FVC in CPFE. Serial FVC measurement used to monitor progression of idiopathic pulmonary fibrosis (IPF) might therefore fail to capture disease progression in CPFE. Objective: To evaluate the relationship between extent of emphysema and disease progression in patients with CPFE. Methods: Patients (n = 309) enrolled previously in a placebo-controlled clinical trial of interferon γ-1b to treat IPF were stratified at baseline based on emphysema extent using HRCT. At week 48, the relationship between emphysema extent and ΔFVC was evaluated. A bootstrap analysis was also performed at 5% intervals of emphysema extent to support these findings. Results: FVC did not decline in patients with an emphysema extent ≥15% while it did in patients with no emphysema (ΔFVC=0.17 vs -4.61; P =0.045). In contrast, patients with an emphysema extent P =0.344; 5-15%, ΔFVC=-4.10 vs -4.61; P =0.733). Bootstrap analysis supported the identified 15% threshold (Figure). Other functional measures (DLco, 6MWT distance, SOBQ and CPI score) were not impacted by emphysema extent. Conclusions: For patients with ≥15% extent of emphysema, the course of FVC decline may be confounded. These findings may inform clinical trial design and care of patients with CPFE.