Optimal Collision Energies and Bioinformatics Tools for Efficient Bottom-up Sequence Validation of Monoclonal Antibodies.

Rigorous validation of amino acid sequence is fundamental in the characterization of original and biosimilar protein biopharmaceuticals. Widely accepted workflows are based on bottom-up mass spectrometry, and they often require multiple techniques and significant manual work. Here, we demonstrate that optimization of a set of tandem mass spectroscopy (MS/MS) collision energies and automated combination of all available information in the measurements can increase the sequence validated by one technique close to the inherent limits. We created a software (called "Serac") that consumes results of the Mascot database search engine and identifies the amino acids validated by bottom-up MS/MS experiments using the most rigorous, industrially acceptable definition of sequence coverage (we term this "confirmed sequence coverage"). The software can combine spectra at the level of amino acids or fragment ions to exploit complementarity, provides full transparency to justify validation, and reduces manual effort. With its help, we investigated collision energy dependence of confirmed sequence coverage of individual peptides and full proteins on trypsin-digested monoclonal antibody samples (rituximab and trastuzumab). We found the energy dependence to be modest, but we demonstrated the benefit of using spectra taken at multiple energies. We describe a workflow based on 2-3 LC-MS/MS runs, carefully selected collision energies, and a fragment ion level combination, which yields ∼85% confirmed sequence coverage, 25%-30% above that from a basic proteomics protocol. Further increase can mainly be expected from alternative digestion enzymes or fragmentation techniques, which can be seamlessly integrated to the processing, thereby allowing effortless validation of full sequences.

Selective 5-HT(1A)-R-agonist repinotan prevents remifentanil-induced ventilatory depression and prolongs antinociception.

BACKGROUND: 5-HT(1A)-R-agonist repinotan was shown to counteract a morphine-induced ventilatory depression but had pronociceptive effects at small doses (0.2 µg/kg). It remained to be clarified (1) whether a moderate dose of repinotan, sufficient to stimulate spontaneous breathing, impairs antinociception if plasma concentration decreases over time, and if (2) moderate doses prevent ventilatory depression if given before the opioid. METHODS: A dose-response curve of the repinotan effects on spontaneous minute ventilation during continuous remifentanil infusion in anesthetized rats was established to identify moderate doses: (1) tail-flick reflex latencies to assess nociception were recorded until 60 min after cessation of a continuous remifentanil infusion with or without a concomitant moderate repinotan dose (10 µg/kg), and (2) remifentanil boluses (2.5 µg/kg) were given after repinotan (10 and 20 µg/kg). RESULTS: (1) Remifentanil-induced antinociception lasted only 5 min after infusion was stopped (tail-flick reflex latencies; median [interquartile range], 97 [54-100]% of maximum possible effect; P = 0.034), but was extended by repinotan (10 µg/kg) to 30 min (tail-flick reflex latencies, 100 [75-100]% of maximum possible effect; P = 0.031). Repinotan (10 µg/kg) alone did not have any significant antinociceptive effect. (2) The ventilatory depression by remifentanil boluses (2.5 µg/kg; minute ventilation, -65 [-81 to -56]%; P = 0.031, n = 5) was blunted by repinotan (20 µg/kg; minute ventilation, -24 [-53 to 13]%; P = 0.313, compared with the pretreatment level). CONCLUSIONS: Repinotan prevented remifentanil-induced ventilatory depression in spontaneously breathing, anesthetized rats. Although repinotan did not depress nociception itself, it prolonged the profound antinociception after discontinuation of remifentanil infusion.

10 kHz spinal cord stimulation for the treatment of chronic back and/or leg pain: Summary of clinical studies.

Chronic pain has a major impact on sufferers and their families. The associated health care costs are substantial. In the context of increasing prevalence, effective treatment options are ever more important. 10 kHz spinal cord stimulation has been shown to effectively provide pain relief, aid in opioid reduction, and improve quality of life in patients with chronic intractable pain. The present review aims to summarize the clinical evidence related to the use of 10 kHz SCS in chronic back and/or leg pain. We searched the PubMed database between 2009 and 2 June 2020 for articles reporting clinical studies that included at least 10 human subjects permanently treated with a 10 kHz SCS system (Senza® system) for chronic back and/or leg pain for a minimum of 3 months. A randomized controlled trial (SENZA-RCT), as well as several prospective and retrospective studies, reported clinical outcomes in subjects with chronic back and leg pain treated with 10 kHz SCS. A high proportion of subjects (60%-80%) reported long-term response to therapy. Pain relief was provided without paresthesia. Other studies showed promising pain relief outcomes in subjects with back pain ineligible for spinal surgery, neuropathic limb pain, and in those with previously failed traditional low-frequency SCS. Most studies reported improved quality of life metrics and/or reduced opioid intake. Level 1 evidence has already been established for the use of 10 kHz SCS in treating chronic back and leg pain, corroborated by real-world, clinical experience. Exploratory studies also show the potential of the therapy in other refractory pain syndromes, although larger studies are desired to validate their findings. Overall, the literature suggests that 10 kHz SCS provides long-term pain relief in a high proportion of patients, along with improved quality of life and reduced opioid consumption.

Cost effectiveness of imatinib mesylate in the treatment of advanced gastrointestinal stromal tumours.

BACKGROUND AND OBJECTIVE: Imatinib mesylate is the first effective therapy for advanced unresectable gastrointestinal stromal tumours (GIST). Adoption of this therapy in clinical practice is partly dependent on reimbursement by third-party payers in many countries. The objective of this study was to estimate the cost effectiveness of imatinib mesylate in the treatment of GIST. METHODS: A cost-effectiveness model of GIST treatment was developed. Long- term survival and duration of imatinib mesylate benefit were projected by fitting curves to 52-month follow-up data from a phase II clinical trial of imatinib and projecting weekly probabilities of survival and continued treatment over 10 years. Weekly cost estimates in 2005 US dollars included cost of imatinib mesylate 400 mg/day ($US685), other medical services for imatinib mesylate-treated patients ($US359) and palliative care for patients in the end stage of GIST ($US2575). Utility associated with successful treatment was estimated at 0.935 and that of treatment failure and progressive disease at 0.875. Costs, life-years and quality- adjusted life-years (QALYs) were calculated over the 10-year time horizon and discounted to treatment initiation at an annual rate of 3%. RESULTS: Imatinib mesylate therapy for unresectable GIST was projected to increase life expectancy to 5.8 years, an increase of 2.7 years over the control group. This translated into an increase of 1.9 QALYs at a marginal cost of $US74 369, yielding a cost-effectiveness ratio of $US38 723 per QALY. Cost effectiveness was not very sensitive to model parameters other than the cost of imatinib mesylate itself. CONCLUSION: The cost effectiveness of imatinib mesylate in the treatment of GIST is within the commonly accepted range for life-saving interventions, based on US data.

Impact of rosuvastatin use on costs and outcomes in patients at high risk for cardiovascular disease in US managed care and medicare populations: A data analysis.

BACKGROUND: High blood cholesterol is a major modifiable risk factor for coronary heart disease (CHD) and stroke. OBJECTIVE: The aim of this study was to estimate the economic impact of rosuvastatin calcium use in patients at high risk for CHD and stroke, according to the National Cholesterol Education Program Adult Treatment Panel (ATP) III guidelines. METHODS: An economic simulation model was developed that used a Markov process to project the number of cardiovascular events and associated costs in a high-risk population in various treatment scenarios. According to the ATP III, high-risk patients are those with CHD, atherosclerosis of peripheral and/or cerebral arteries, diabetes, and/or multiple other risk factors conferring a risk of at least 20% within 10 years. Data on population characteristics and costs of cardiovascular disease (CVD) were obtained from claims data sets from employer-funded commercial and Medicare health plans in the United States. Treatment of lipid disorders was translated into CVD risk reduction based on results from the Heart Protection Study. The estimated efficacies of individual lipid-lowering drugs were based on data published in package inserts. The model generated costs at the health plan level of lipid-lowering therapy in high-risk patients and the number and total costs of cardiovascular events. Estimates were compared for scenarios representing the mix of treatments used before and after the introduction of rosuvastatin. Estimates were generated separately for commercial and Medicare health plans. RESULTS: For every 1 million members of a commercial health plan, an estimated 44,457 met ATP III criteria for high-risk status. Use of rosuvastatin in place of other 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ("statins") by 11 % of these patients over a period of 5 years was estimated to result in 36 fewer cardiovascular events and a net savings of US 4.03 million dollars. A Medicare plan of 1 million members with an estimated 433,268 high-risk patients and 7% rosuvastatin use was estimated to avoid 727 events and save US 34.32 million dollars. CONCLUSIONS: The results of this data analysis suggest that increasing the use of rosuvastatin can result in cardiovascular event reduction and cost savings. Because the impact of lipid-modifying therapy on cardiovascular risk has not been thoroughly documented in controlled clinical studies, our model assumed that incremental lipid changes had effects in proportion to the magnitude of change.

Patterns of initial pharmacotherapy for Parkinson's disease in the United States.

Data from a mix of employer- and government-funded health plans were used to investigate actual treatment patterns for patients initiating pharmacotherapy for Parkinson's disease in the United States. Treatment patterns evaluated included type of initial therapy and rates and types of adjunctive and substitute therapies. The study confirms that levodopa remains the most often prescribed initial treatment for Parkinson's disease regardless of age or drug benefit coverage. The widespread use of levodopa in young Parkinson's patients (<65 years) with private insurance may indicate that physicians are not overly concerned about or are not fully aware of the association of levodopa with long-term motor complications. It may also indicate that currently available alternatives to levodopa are not sufficiently effective or well tolerated.

Cost effectiveness of adding ezetimibe to atorvastatin therapy in patients not at cholesterol treatment goal in Canada.

INTRODUCTION: This analysis compared the cost effectiveness of adding ezetimibe to atorvastatin therapy versus atorvastatin titration or adding cholestyramine (a resin) for patients at high risk of a coronary artery disease (CAD) event who did not reach target cholesterol levels on their current atorvastatin dosage. The primary analysis focused on 65-year-old patients with low-density lipoprotein cholesterol (LDL-C) levels of 3.1 or 3.6 mmol/L with a treatment goal of <2.5 mmol/L, classified as very high risk according to the 2000 Canadian Guidelines for Management and Treatment of Hyperlipidaemia. METHODS: A previously developed Markov model was utilised to capture the cost and clinical consequences of lipid-lowering therapy in primary and secondary prevention of CAD. Comparisons between treatment strategies were made using ICERs (cost per QALY) from a Canadian Ministry of Health perspective. The effects of lipid-lowering therapies were based on clinical trial data. The risks of CAD events were estimated using Framingham Heart Study risk equations. Treatment costs and the costs of acute and long-term care for CAD events were included in the analysis. Costs (Canadian dollar, 2002 values) and outcomes were discounted at 5% per annum. RESULTS: Ezetimibe added to atorvastatin therapy compared with treatment with the most common fixed atorvastatin daily dosage (10 mg) or with common atorvastatin titration strategies (up to 20 mg daily; up to 40 mg daily) resulted in cost per QALY estimates ranging from 25,344 to 44,332 Canadian dollars. The addition of ezetimibe to atorvastatin therapy was less costly and more effective than the addition of cholestyramine (dominant). CONCLUSION: Our analysis suggests that adding ezetimibe to atorvastatin for patients not achieving treatment goals with their current atorvastatin dose produces greater clinical benefits than treatment with a fixed-dose atorvastatin or atorvastatin titration at an increased overall cost. The cost-effectiveness ratios provide strong evidence for the adoption of ezetimibe within the Canadian healthcare system.

A projection of the impact of lipid-lowering therapy on high-risk employee disability and medical costs.

OBJECTIVE: The objective of this study was to examine the impact of introducing rosuvastatin calcium on direct and indirect costs among patients at high risk for coronary heart disease. METHODS: An economic simulation model was developed to project the number of cardiovascular events and associated direct and indirect costs under varying treatment scenarios. RESULTS: In an average-sized commercial health plan with 210,000 covered lives and 9,336 high-risk patients, an uptake of rosuvastatin by 11% of high-risk patients would result in eight fewer cardiovascular events, a net savings of 0.85 million dollars in direct medical costs and a net savings of 36,404 dollars in productivity loss over a period of 5 years. The overall reduction in total costs is equivalent to 1735 dollars per rosuvastatin-treated patient. CONCLUSIONS: At current statin prices, the use of rosuvastatin could lead to fewer cardiovascular events and lower direct and indirect costs.

Impact of leflunomide versus biologic agents on the costs of care for rheumatoid arthritis in a managed care population.

OBJECTIVE: To compare the impact of leflunomide on resource utilization and costs relative to that of etanercept and infliximab among patients with rheumatoid arthritis (RA) in a managed care setting. METHODS: Data were obtained from the PharMetrics Integrated Outcomes Database for all patients newly starting 1 of the 3 medications of interest in 1999 or 2000. Claims were compiled for 180 days prior to the first prescription for study therapy and for a minimum of 90 days thereafter. Measures of interest during follow-up included the incidence of significant interventions (eg, joint injection, synovectomy), 1-year utilization of study therapy, other RA-related medications, inpatient and outpatient services, and total costs of RA-related care. Data were adjusted for variable follow-up using survival techniques. Multivariate analyses were conducted on total costs, controlling for between-group differences in demographic, clinical, and pretreatment characteristics. RESULTS: A total of 4069 patients were included in the study cohort (n = 2217, 1547, and 305 for leflunomide, etanercept, and infliximab, respectively). Three quarters of the cohort were female; etanercept patients were somewhat younger than leflunomide or infliximab recipients. Severity of illness (as measured by the Charlson index) was highest among infliximab patients. The incidence of significant interventions was high in all patients, but did not differ by treatment group. Use of nonsteroidal anti-inflammatory drugs (8.1 versus 8.9 claims) and narcotic analgesics (7.8 versus 8.5) was substantially lower for leflunomide than for etanercept. Costs of RA-related care were 42% to 53% lower among leflunomide patients for biologic medications ($9618 versus $16,534 and $20,263 for etanercept and infliximab, respectively), primarily as a result of lower medication costs. Findings persisted in multivariate analyses of cost. CONCLUSIONS: Leflunomide is associated with reduced costs of medications and other healthcare services relative to biologic medications among managed care patients with RA.

Outpatient treatment of venous thromboembolism with low-molecular-weight heparin: an economic evaluation.

BACKGROUND: The development of low-molecular-weight heparins (LMWHs) has made it possible to shift treatment of deep vein thrombosis (DVT) from inpatient to outpatient settings, thereby saving costs and improving patient quality of life. OBJECTIVE: To quantify the economic benefits of early discharge of patients treated for DVT with LMWH using data pooled from multiple healthcare plans. METHODS: Data sources were integrated medical and pharmacy claims paid by 37 US health plans (the PharMetrics Integrated Outcomes Database, PharMetrics, Inc., Watertown, MA). Hospitalized patients discharged with a diagnosis of DVT were selected and grouped according to the anticoagulation therapy they received after discharge. Outcomes and costs of DVT treatment were assessed over a 1-year period. RESULTS: Patients discharged on the LMWH enoxaparin and warfarin spent 2.6 fewer days in the hospital than those discharged on warfarin alone (P< .0001), resulting in cost savings of $1911 per patient. Mean costs of outpatient management of DVT, including pharmacy and medical services, were $901 higher in the enoxaparin/warfarin cohort, but rate of readmission was lower (6.7% versus 9.0%; P < .05) and hence subsequent inpatient costs were reduced by $140 per patient. Total cost savings in the enoxaparin/warfarin cohort, net of higher outpatient costs, were $1151 per patient. CONCLUSIONS: Outpatient anticoagulation therapy for DVT with enoxaparin and warfarin is associated with earlier hospital discharge, fewer readmissions, and lower total DVT-related costs compared with warfarin monotherapy.

Use of managed care claims data in the risk assessment of venous thromboembolism in outpatients.

BACKGROUND: Deep vein thrombosis (DVT) is a complication of immobilizing illness in both inpatient and outpatient settings and can lead to serious complications such as pulmonary embolism (PE). DVT and PE are collectively referred to as venous thromboembolism. OBJECTIVE: To develop DVT and PE risk assessment models that can be used in office-based practice and for population-based disease management efforts. METHODS: Data were culled from integrated medical and pharmacy claims paid by 37 health plans in the United States (the PharMetrics Integrated Outcomes Database, PharMetrics Inc., Watertown, MA), and included information on adult plan members enrolled during 1998 and 1999. Patients hospitalized for DVT or PE in 1999 were identified, and potential risk factors were assessed by reviewing claims for the entire study population in 1998 to document prior DVT or immobilizing illness. The contribution of each potential risk factor to the probability of the occurrence of DVT or PE was determined by means of multiple logistic regression analysis. A risk-scoring algorithm based on regression coefficients was then developed. RESULTS: Fifty-two percent of the study population of 2.8 million plan members were women. DVT or PE occurred in 1330 of those 2.8 million individuals (47 per 100,000). Logistic regression results confirmed the role of risk factors previously reported in the literature and revealed additional risk factors that have not been reported previously, including diabetes, renal failure, rheumatoid arthritis, cellulitis, use of warfarin, use of systemic corticosteroids, and use of potassium chloride. When risk scores were applied to the study population, the 1% identified as being at highest risk had a probability for the development of venous thromboembolism that was 10 times greater than that of the population average. CONCLUSIONS: This study confirms the feasibility of using managed care claims data to develop a risk assessment tool for venous thromboembolism that can be used in office-based practice and for population-based disease management.

Incidence of genitourinary conditions in women with a diagnosis of vulvar/vaginal atrophy.

OBJECTIVES: Vulvar/vaginal atrophy (VVA) is one genitourinary condition associated with a decline in estrogen. This may be bothersome for women following menopause. Although the clinical features of VVA and other conditions after menopause have been documented, few studies have quantified the magnitude of association between VVA and other genitourinary conditions. METHODS: A VVA cohort was identified from two United States administrative claims databases. A matched cohort of an equal number of controls was randomly selected from a pool of women 40-79 years of age without VVA. Baseline characteristics and medical history were tabulated for the VVA cohort and matched controls. Six genitourinary conditions ('urinary tract infections', 'other/unspecified genitourinary symptoms', 'other inflammatory diseases of female pelvic organs', 'menopausal disorders', 'female genital pain and other symptoms', and 'other/unspecified female genital disorders') were hypothesized a priori to be associated with VVA. Adjusted incidence rate ratios measured the strength of association of VVA with each condition. RESULTS: A total of 9080 women aged 40-79 years with newly diagnosed VVA during 2000-2010 were identified. The mean age of VVA patients and matched controls was 60.2 years. At baseline, a significantly (p < 0.001) higher proportion of women in the VVA cohort had a diagnosis of angina, osteoporosis, migraines, insomnia, or anxiety, or received estrogen supplementation or selective estrogen receptor modulators. VVA patients had a significantly (p < 0.001) higher incidence of each of the genitourinary conditions compared to controls. The condition most strongly associated with VVA with a relative risk of 6.2 was 'other inflammatory diseases of female pelvic organs'. CONCLUSIONS: Women with VVA have a greater risk of genitourinary conditions compared to those without. The overall prevalence of VVA and other genitourinary conditions may be underreported as claims data only captures information for patients under medical care and many women do not seek consultation for VVA symptoms.

Interaction of [Ru(η6-p-cym)(H2O)3]²âº with citrate and tricarballate ions in aqueous solution; X-ray crystal structure of novel half-sandwich Ru(II)-citrato complexes.

The interaction between [Ru(η(6)-p-cym)(H(2)O)(3)](2+) and an important low molecular weight serum component, citric acid (citrH(3)), was studied with the aid of combined pH-potentiometric, (1)H NMR, (13)C NMR and electrospray ionization mass spectrometry (ESI-MS) methods in aqueous solution. For comparative purposes propane-1,2,3-tricarboxylic acid (tricarballylic acid, tricH(3)) having no alcoholic-OH group in position 2 was also investigated. Stoichiometries, stability constants and the most plausible solution structures of the complexes formed in the systems were determined. Depending upon the pH, citrate was found to coordinate to the metal ion via [COO(-), COO(-), OH] or [COO(-), COO(-), O(-)] fashion yielding mononuclear complexes with high stability. As a consequence at physiological pH the hydrolysis of the metal ion is completely hindered even at 1:1 metal to ligand ratio. Crucial role of the alcoholic/alcoholate function of the citric acid in [Ru(η(6)-p-cym)(H(2)O)(3)](2+) binding is reflected in the low stability of the species formed with tricarballylic acid. The X-ray crystal structures of [Ru(η(6)-p-cym)(citrH)]·H(2)O·CH(3)OH and 2[Ru(η(6)-p-cym)(citrH)]·3H(2)O being the first published structures of an organometallic Ru(II)-citrate and both featuring a [COO(-), COO(-), OH] coordinated ligand, are also reported.

Adult ADHD: prevalence of diagnosis in a US population with employer health insurance.

OBJECTIVE: The burden of attention-deficit/hyperactivity disorder (ADHD) in adults is increasingly recognized. This retrospective analysis was designed to estimate the prevalence of diagnosed ADHD in a population of insured, employed individuals and their dependents in the United States. METHODS: Health care claims data obtained from the MarketScan Commercial Claims and Encounters Database were analyzed. Patients with ADHD were identified by at least two diagnostic claims per calendar year. Once identified, patient records were examined for evidence of continuing ADHD. RESULTS: Between 2002 and 2007, the MarketScan database identified 342,284 patients with more than one claim for ADHD. Of these, 79,368 patients met the eligibility for the prevalence estimates. During the study period, the prevalence of diagnosed ADHD among adults increased more than three-fold: 1.24 to 4.02 cases per 1000 covered members. The largest proportion of cases was in the 18-24 years age group (42.8%-45.8% per year). Most cases were males; however, the ratio of females-to-males diagnosed increased over time. ADHD with hyperactivity was prevalent across all age groups analyzed, although more common in the 18-24 years group. Pharmacy claims showed patients receiving medical treatment for ADHD increased from 78% to 88.5%. A limitation of this study is that it is restricted to employed persons and their dependents. Thus, the results from this database may underestimate the true prevalence of diagnosed ADHD in the US population. CONCLUSIONS: While the claims database used included employed insured persons and dependents only, study results highlight the rising prevalence of diagnosed ADHD in a US adult population. The prevalence increased more than three-fold from 2002 to 2007 with the largest increase in the 18-24 years age group. These findings on ADHD prevalence highlight the need for greater attention to the medical treatment of this disorder in different age groups, particularly in young adults.

Cost effectiveness of tyrosine kinase inhibitor therapy in metastatic gastrointestinal stromal tumors.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) such as imatinib mesylate have revolutionized the treatment of primary unresectable and/or metastatic gastrointestinal stromal tumors (GISTs), providing durable disease control and extended survival. Although most patients eventually progress on therapy, dose escalation has been shown to benefit some patients. Sunitinib, a multitargeted kinase inhibitor is effective against imatinib-resistant or intolerant GIST patients. Although the cost of TKI therapy in GIST is high, no other effective systemic treatment options exist. OBJECTIVE: Review pharmacoeconomic studies to determine the cost effectiveness (CE) of 1st- and 2nd-line TKI therapies in GIST. METHODS: A literature review using Medline and PubMed databases was conducted to identify published economic analyses of TKI therapy in GIST. Key results from these studies were analyzed. RESULTS: Six pharmacoeconomic studies were identified, including three analyses of 1st-line imatinib and three analyses of 2nd-line sunitinib. These studies employed various time horizons and discount rates and modeled CE from a number of different perspectives. Most of the pharmacoeconomic studies reviewed used survival as their efficacy endpoint, projecting outcomes beyond available data to model CE. Analyses of 2nd-line sunitinib using survival additionally faced the challenge of adjusting for the effect of placebo crossover to active treatment in the pivotal phase III study. Most studies used Markov techniques with a range of transition probabilities. CONCLUSIONS: Published pharmacoeconomic studies of 1st- and 2nd-line TKI therapy for advanced GIST employ various time horizons, discount rates, and different CE models. Consequently, these differences make comparisons between studies difficult. Studies of 1st-line imatinib concluded that imatinib was cost effective in advanced, metastatic GIST. Likewise, based on data reviewed here, 2nd-line sunitinib appears to be cost effective in patients with advanced GIST who are intolerant/resistant to imatinib. Key limitations of this review included inconsistency among the studies evaluated with regard to methodologies, countries of origination (currency and healthcare systems), and patient demographics.

Burden of illness in Parkinson's disease.

This study quantifies direct medical care costs for individual patients with Parkinson's disease (PD) and projects total national costs of PD. Anonymous, patient-level data on health care utilization and cost were obtained from Medstat's MarketScan Research Databases. Patients were selected for study if they had either two instances of a diagnosis of PD or one diagnosis and two or more prescriptions for PD-related medication. A control group of persons without PD was selected for comparison. Total annual health care utilization and costs were calculated for both PD patients and controls. A total of 20,016 patients with PD were identified and followed up for an average of 853 days. The mean age of the patients was 73.6 years, and 51.2% were women. Total annual direct costs were 23,101 US Dollars (SD 27,529) per patient with PD versus 11,247 US Dollars (SD 16,486) for controls. The regression-adjusted incremental direct cost of PD versus control was 10,349 US Dollars (95% confidence interval, 9,053, 11,645). Adding 25,326 US Dollars in indirect costs, and multiplying by 645,000 cases of PD in the United States, the total cost to the nation is projected to be 23 billion US Dollars annually. This estimate is higher than most previous studies, with important implications for health care delivery systems worldwide.

Consequences of increased systolic blood pressure in patients with osteoarthritis and rheumatoid arthritis.

OBJECTIVE: To estimate the potential effect on cardiovascular event occurrence and treatment costs associated with increases in systolic blood pressure (SBP) among patients with osteoarthritis (OA) and rheumatoid arthritis (RA). METHODS: We used cardiovascular risk prediction models from the Framingham Heart Study and data on risk factors from the Third National Health and Nutrition Examination Survey (NHANES III) to estimate occurrences of ischemic heart disease and stroke over one year among US adults with OA/RA. Separate analyses were conducted for treated hypertensive patients, and untreated hypertensive and normotensive patients, respectively. Published estimates were used to assign costs to these events and to follow care. The effect of incremental increases in SBP on events and costs was then assessed. Monte Carlo simulation was undertaken to assess the range of event occurrence and costs associated with alternative assumptions regarding the distribution of increased SBP in the at-risk population. RESULTS: Of the estimated 30 million adults in the US aged > or = 35 years with OA and RA, roughly 11.8 million (39%) receive pharmacologic treatment for hypertension. Increases in SBP of 1-5 mm Hg were associated with 7,100-35,700 additional ischemic heart disease and stroke events over one year, with corresponding costs (year 2000 USD) of 114-569 million year 2000 USD. A 20 mm Hg increase in SBP experienced by 15% of the at-risk population (equivalent to a population-average 3 mm Hg increase) is associated with about 21,700 additional events (95% CI 19,120, 24,221) and 346 million year 2000 USD (95% CI 305 year 2000 USD, 387 million) in associated costs. CONCLUSION: Relatively small changes in SBP associated with use of common arthritis medications can have a significant effect on the cardiovascular risk profile. It is important that clinicians who treat patients with OA/RA accurately weigh the potential risks of these medications against their benefits.