External validation of the In-hospital Mortality for PulmonAry embolism using Claims daTa (IMPACT) multivariable prediction rule.

OBJECTIVE: To validate the In-hospital Mortality for PulmonAry embolism using Claims daTa (IMPACT) multivariable prediction rule using admission claims data. STUDY DESIGN: Retrospective claims database analysis. METHODS: This analysis was performed using Humana admission claims data from January 2007 to March 2014. We included adult patients admitted for their first PE during this period (International Classification of Diseases, ninth edition, Clinical Modification code of 415.1x in in the primary position or secondary position when accompanied by a primary code for a PE complication). The IMPACT rule, consisting of age plus 11 comorbidities, was used to estimate patients' probability of in-hospital mortality and classify risk. Low risk was defined as in-hospital mortality ≤ 1.5%. IMPACT was evaluated by evaluating prognostic test characteristic values and 95% confidence intervals (CIs). RESULTS: A total of 23,858 patients admitted for PE were included, and 3.3% died in-hospital. The IMPACT prediction rule classified 2371 (9.9%) as low-risk; with a sensitivity of 97.6%, 95% CI: 96.1-98.5, specificity of 10.2%, 95% CI: 9.8-10.6, negative and positive predictive values of 99.2% (95% CI: 98.7-99.5) and 3.5% (95% CI: 3.3-3.8) and c-statistic of 0.70, 95% CI: 0.0.68-0.72, for in-hospital mortality. IMPACT classified 42.7% of patients < 65 years old as low-risk; with a sensitivity, specificity and c-statistic of 85.0%, 95% CI: 77.4-90.5, 43.3%, 95% CI: 42.0-44.7 and 0.74, 95% CI: 0.69-0.78, respectively. CONCLUSION: The IMPACT prediction rule was valid when implemented in a database consisting largely of Medicare claims. Following further external validation and direct comparison to commonly used clinical prediction rules, IMPACT may become a valuable tool for payers and hospitals wishing to retrospectively assess whether their PE patients are being kept hospitalized for the optimal period of time.

Incidence of hospital readmission in patients diagnosed with DVT and PE: clinical burden of recurrent events.

BACKGROUND: Venous thromboembolism (VTE), which comprises deep-vein thrombosis (DVT) and pulmonary embolism (PE), is associated with significant morbidity and mortality and represents a considerable economic burden to the US healthcare system. Although it is well established that patients with an initial VTE are at increased risk for recurrent VTE, limited data exist on the clinical burden of a secondary DVT or PE event. The objective of this retrospective observational study was to conduct an epidemiologic evaluation, from a hospital perspective, of patients with an initial DVT or PE who experienced a recurrent event postdischarge requiring hospital readmission. METHODS: Hospital claims containing DVT or PE as a primary diagnosis for hospitalisation during the period October 2009 to April 2013 were identified by retrospective analysis using the MarketScan database. The time to hospital readmission for DVT or PE was assessed using the MarketScan Treatment Pathways tool. RESULTS: Of 214,901 patient admissions identified with a diagnosis of DVT or PE at hospital admission, approximately 4% were subsequently readmitted to the hospital with a diagnosis of PE (8217) or DVT (9138). Of all readmitted patients with a diagnosis of DVT on initial admission, 66% were rehospitalised with a diagnosis of DVT, and 34% were rehospitalised with a diagnosis of PE. Of all readmitted patients with a diagnosis of PE on initial admission, 63% were rehospitalised with a diagnosis of PE and 37% with a diagnosis of DVT. Of all hospital readmissions with a diagnosis of PE or DVT, 62% and 58% occurred within the first 30 days following an initial PE or DVT event, respectively. CONCLUSIONS: The burden of DVT or PE is large, not only because of the initial hospitalisation event but also because of the high number of hospital readmissions, more than half of which occur within 30 days.

Prasugrel vs. clopidogrel in acute coronary syndrome patients treated with prasugrel.

WHAT IS KNOWN AND OBJECTIVE: Current guidelines recommend a combination of clopidogrel and aspirin for management of patients who have experienced an acute coronary syndrome (ACS). Additional antiplatelet agents have been recently approved. Few comparative effectiveness studies are available for these new agents. Accordingly, we evaluated effect on time to hospital admission and resource utilization (number of hospitalizations, ER visits and outpatient visits) of prasugrel vs. clopidogrel in prasugrel-treated patients as assessed in a matched cohort. METHODS: Based on the Truven Health Analytics MarketScan database from 01 January 2009 through 31 July 2012, a retrospective prasugrel-clopidogrel matched cohort was created. Inferences for average treatment effect over 1 and 12 months on time to hospitalization and resource utilization were performed by (i) frequentist Kaplan-Meier estimation with a Cox proportional hazard model and Lin's cost history method for censored resource utilization outcomes and (ii) Bayesian discrete-time hazard and negative binomial models. RESULTS AND DISCUSSION: The 10,963 matched pairs were well balanced on baseline characteristics. Frequentist analyses of time to hospital admission over 365 days and mean all-cause resource utilization over 30 and 365 days showed no statistical differences between prasugrel and clopidogrel (P-values > 0·05). Based on Bayesian analysis of time to admission over 12 months, there was positive evidence of equivalence (0·987 probability of equivalence at a 10% equivalence margin and a Bayes factor of 0·611). Although the frequentist analyses for number of all-cause hospitalizations showed a lack of a significant difference at Months 1 and 12, the Bayesian data analysis showed positive evidence of superiority of clopidogrel at Month 1 (Bayes factor: 5·369); however, at Month 12, there was little evidence of superiority of one treatment over the other (Bayes factor: 0·422). WHAT IS NEW AND CONCLUSION: Using frequentist and Bayesian data analyses, in prasugrel-treated patients, clopidogrel was equivalent to prasugrel for time to hospital admission over 12 months and there was positive evidence that it was superior to prasugrel for number of hospitalizations over the first month of treatment.

Economic benefit of a 1-day reduction in hospital stay for community-acquired pneumonia (CAP).

OBJECTIVE: As a component of healthcare reform, payers, hospital administrators, and physicians are looking for ways to reduce hospital expenditures and improve efficiency. The economic benefit of a reduced hospital stay must be weighed against the cost of the treatment or process necessary to achieve the reduced length of stay (LOS). The objective of this paper was to estimate the potential economic benefit of a reduction in inpatient hospital LOS for a common type of admission, community acquired pneumonia (CAP). RESEARCH DESIGN AND METHODS: Data for this study were from the CAP hospital admissions selected from the 2006 Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS). Potential savings associated with a 1 day reduction in CAP LOS were estimated using three methods: (1) average cost, (2) weighted-average incremental cost of an additional day, and (3) weighted-average predicted mean costs from regression models which were used to estimate incremental cost adjusting for hospitalization characteristics. MAIN OUTCOME MEASURES: Cost per day of CAP hospitalization. RESULTS: A total of 1,471,295 CAP admissions qualified for the analysis. The cost for each day of reduction in LOS in 2009 US dollars was $2273, $2373, and $2319 for the three methods: simple average, incremental, and regression, respectively. Subgroup analysis and regression analysis indicated higher costs were identified: in patients who died in the hospital, had hospital stays in the Northeast or West, and in large hospitals. Longer CAP hospitalizations had a higher cost per additional day. Limitations include those typically associated with the use of administrative claims (e.g., lack of clinical detail, issues related to diagnosis coding). CONCLUSIONS: Eliminating a day during the course of a CAP admission is potentially worth $2273-2373 in economic benefits (2009 dollars). As we strive for greater efficiency in healthcare delivery, changes in processes and/or improved diagnostics or treatments may potentially achieve a reduction in the length of stay. The cost of such changes or improvements must be weighed against the economic benefit of a shorter hospitalization.

Medical resource utilization among community-acquired pneumonia patients initially treated with levofloxacin 750 mg daily versus ceftriaxone 1000 mg plus azithromycin 500 mg daily: a US-based study.

OBJECTIVE: The 2007 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines recommend that community-acquired pneumonia (CAP) patients admitted to hospital wards initially receive respiratory fluoroquinolone monotherapy or beta-lactam plus macrolide combination therapy. There is little evidence as to which regimen is preferred, or if differences in medical resource utilization exist between therapies. Thus, the authors compared length of hospital stay (LOS) and length of intravenous antibiotic therapy (LOIV) for patients who received initial levofloxacin 750 mg daily versus ceftriaxone 1000 mg plus azithromycin 500 mg daily ('combination therapy'). RESEARCH DESIGN AND METHODS: Adult hospital CAP cases from January 2005 to December 2007 were identified by principal discharge diagnosis code. Patients with a chest infiltrate and medical notes indicative of CAP were included. Direct intensive care unit admits and healthcare-associated cases were excluded. A propensity score technique was used to balance characteristics associated with initial antimicrobial therapy using multivariable regression to derive the scores. Propensity score categories, defined as propensity score quintiles, rather than propensity scores themselves, were used in the least squares regression model to assess the impact of LOS and LOIV. RESULTS: A total of 495 patients from six hospitals met study criteria. Of these, 313 (63%) received levofloxacin and 182 (37%) received combination therapy. Groups were similar with respect to age, sex, most comorbidities, presenting signs and symptoms, and Pneumonia Severity Index (PSI) risk class. Patients on combination therapy were more likely to have heart failure and receive pre-admission antibiotics. Adjusted least squares mean (+/-SE) LOS and LOIV were shorter with levofloxacin versus combination therapy: LOS, 4.6 +/- 0.17 vs. 5.4 +/- 0.22 days, p < 0.01; and LOIV, 3.6 +/- 0.17 vs. 4.8 +/- 0.21 days, p < 0.01. Results for PSI risk class III or IV patients were: LOS, 5.0 +/- 0.30 vs. 5.9 +/- 0.37 days, p = 0.07; and LOIV, 3.7 +/- 0.33 vs. 5.2 +/- 0.39 days, p < 0.01. Due to the retrospective study design, limited sample size, and scope (single health-network), the authors encourage replication of this study in other data sources. CONCLUSIONS: Given the LOS and LOIV reductions of 0.8 and 1.2 days, respectively, utilization of levofloxacin 750 mg daily for CAP patients admitted to the medical floor has the potential to result in substantial cost savings for US hospitals.

Patient satisfaction with oral versus nonoral therapeutic approaches in onychomycosis.

The follow-up results of a 9-month observational study of 150 onychomycosis patients treated with a variety of mechanical, topical, and oral therapies by podiatric physicians and dermatologists are presented. Changes from baseline in toenail condition and patient satisfaction were assessed at 4- and 9-month follow-up. At 9 months, patients who had received oral therapy reported significantly fewer onychomycosis-related problems in social situations, including embarrassment or self-consciousness about the appearance of nails, avoidance of contact by others, being perceived as unclean or untidy, and the desire to keep their nails concealed. Patient-reported satisfaction with the treatment program was significantly higher for those receiving oral therapy than for those receiving nonoral therapy.

Comparative safety of bone remodeling agents with a focus on osteoporosis therapies.

This article reviews the different treatments currently available for osteoporosis and examines the benefits and adverse events that are associated with each. While emphasizing safety considerations, this review summarizes the following treatments for osteoporosis: calcium supplements, fluoride, hormone replacement therapy, raloxifene, bisphosphonates, salmon calcitonin, and calcitriol. Before prescribing any of these agents, the clinician should review the risk/benefit profile of each drug in the context of the individual patient's history, concomitant diseases, concurrent medications, and general physical condition.

Osteoporosis therapies for rheumatoid arthritis patients: minimizing gastrointestinal side effects.

OBJECTIVE: This manuscript identifies characteristics that put people with rheumatoid arthritis (RA) at high risk for osteoporosis or gastrointestinal (GI) disturbances. The manuscript then reviews therapies available for osteoporosis in the United States and makes recommendations about choosing therapies that minimize GI adverse effects in RA patients at high risk for such events. DATA SOURCES: References identified through MEDLINE, abstracts, and prescribing information for individual drugs. DATA EXTRACTION: Characteristics that predispose patients to osteoporosis and GI problems were identified. Data on individual osteoporosis therapies were assessed by risk-benefit analysis and appropriateness for use in patients at risk for GI disturbances. DATA SYNTHESIS: High risk of osteoporosis in people with RA is caused by disease activity, medication effects, physical inactivity, and standard risk factors such as postmenopausal status and increased age. Patients with RA are frequently at high GI risk if they are receiving nonsteroidal anti-inflammatory drugs or corticosteroids. Because of the high potential for erosive esophagitis and other upper GI disorders with alendronate, caution is warranted in prescribing alendronate to RA patients with high GI risk. In such patients, estrogen replacement therapy, selective estrogen receptor modulators, or calcitonin should be considered for treatment, and either estrogen replacement therapy or selective estrogen receptor modulators should be considered for osteoporosis prevention. CONCLUSIONS: Assessment of GI risk is important in patients with RA and osteoporosis. Risk factors should be considered when choosing osteoporosis therapies.

Diagnosis and treatment of nonsteroidal anti-inflammatory drug-associated upper gastrointestinal toxicity.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed in the United States to treat pain and reduce inflammation from chronic inflammatory disorders such as rheumatoid arthritis and osteoarthritis. Approximately 40% of older Americans take NSAIDs. Chronic NSAID use carries a risk of peptic ulcer and other gastrointestinal disturbances. This article reviews the diagnosis of medication-induced ulcers based on clinical presentation, laboratory tests, and endoscopic findings to assist the clinician in early diagnosis and appropriate therapy. Risk factors for NSAID-induced ulcers include old age, poor medical status, prior ulcer, alcoholism, smoking, high NSAID dosage, prolonged NSAID use, and concomitant use of other drugs that are gastric irritants, such as alendronate, a bone resorption inhibitor prescribed for osteoporosis. Appropriate treatment options for patients with medication-induced ulcers include dosage reduction, medication substitution, medication withdrawal, antiulcer therapy, and discontinuation of other gastrotoxic drugs.

Perceived risks and reported behaviors associated with osteoporosis and its treatment.

This study investigates older American women's knowledge and risk perceptions about osteoporosis and its treatment. Our results indicate that older U.S. women undervalue the health impact of osteoporosis; they consider it controllable, and neither life threatening nor dreaded relative to other possible diseases or conditions. At least 1/3 of older women in a diagnosed and general sample also confused osteoporosis with arthritis. Women scored highest on osteoporosis knowledge questions related to items under their personal control, such as diet or exercise. Further, women who understood the effects of a particular behavior on osteoporosis were more likely to act in accordance with that knowledge than were women who did not understand those effects.

A health-related quality of life measure for use in patients with onychomycosis: a validation study.

Onychomycosis is a common nail disorder associated with pain, discomfort and varying degrees of physical impairment and loss of dexterity. Psychological and social limitations result from reactions of others to visible impairment. The goal of this research is to validate a questionnaire to measure the impact of toenail onychomycosis on health-related quality of life (HRQoL). One hundred and fifty onychomycosis patients were enrolled in an observational study at eight sites in the US. Attending physicians reported information on clinical status at enrolment. Patients completed a questionnaire covering HRQoL that included general and disease-specific items measuring the impact of onychomycosis on activities and appearance, plus problems and symptoms associated with toenail infection. The subscales of the instrument showed high internal consistency reliability (range = 0.63-0.95). Construct validity reflected the close association of physical functioning scores with onychomycosis impairment. Test-Retest reliability was good to excellent for all scales (ICC = 0.52-0.89). Discriminant validity was evidenced by persons who are younger and female reporting worse disease-specific HRQoL. Responsiveness to clinical change was noted for all disease-specific scale scores for improved patients. This instrument has demonstrated reliability, validity and responsiveness for use in observational and clinical studies of toenail onychomycosis patients. Data indicate that onychomycosis patients report significant pain and discomfort reflecting the need for HRQoL measurement.

Influence of low HDL on progression of coronary artery disease and response to fluvastatin therapy.

BACKGROUND--Patients with coronary artery disease (CAD) commonly have low HDL cholesterol (HDL-C) and mildly elevated LDL cholesterol (LDL-C), leading to uncertainty as to whether the appropriate goal of therapy should be lowering LDL-C or raising HDL-C. METHODS AND RESULTS--Patients in the Lipoprotein and Coronary Atherosclerosis Study (LCAS) had mildly to moderately elevated LDL-C; many also had low HDL-C, providing an opportunity to compare angiographic progression and the benefits of the HMG-CoA reductase inhibitor fluvastatin in patients with low versus patients with higher HDL-C. Of the 339 patients with biochemical and angiographic data, 68 had baseline HDL-C <0.91 mmol/L (35 mg/dL), mean 0.82+/-0.06 mmol/L (31. 7+/-2.2 mg/dL), versus 1.23+/-0.29 mmol/L (47.4+/-11.2 mg/dL) in patients with baseline HDL-C >/=0.91 mmol/L. Among patients on placebo, those with low HDL-C had significantly more angiographic progression than those with higher HDL-C. Fluvastatin significantly reduced progression among low-HDL-C patients: 0.065+/-0.036 mm versus 0.274+/-0.045 mm in placebo patients (P=0.0004); respective minimum lumen diameter decreases among higher-HDL-C patients were 0. 036+/-0.021 mm and 0.083+/-0.019 mm (P=0.09). The treatment effect of fluvastatin on minimum lumen diameter change was significantly greater among low-HDL-C patients than among higher-HDL-C patients (P=0.01); among low-HDL-C patients, fluvastatin patients had improved event-free survival compared with placebo patients. CONCLUSIONS--Although the predominant lipid-modifying effect of fluvastatin is to decrease LDL-C, patients with low HDL-C received the greatest angiographic and clinical benefit.

Maximizing the cost-effectiveness of lipid-lowering therapy.

Cardiovascular disease, including coronary heart disease, is the leading cause of death both in men and in women in the United States. The purpose of this review is to describe the effectiveness of lipid-lowering therapy in reducing cardiovascular morbidity and mortality, which has recently been extended to patients with mild to moderate hypercholesterolemia, and the cost of providing therapy, which would be prohibitive if all persons with hypercholesterolemia received treatment. Cost-effectiveness analysis provides a rational means of allocating limited health care resources by allowing the comparison of the costs of lipid-lowering therapy, in particular, therapy with beta-hydroxy-beta-methylglutaryl-CoA (coenzyme A) reductase inhibitors (statins), with the costs of atherosclerosis that could be prevented by lowering cholesterol. To extend the benefits of treatment to the large number of persons not receiving therapy, we need to implement more cost-effective treatment by improving risk assessment, increasing treatment effectiveness, and reducing the cost of therapy.

Epidemiology, outcomes research, and drug interactions.

Drug interactions are one of several outcomes (typically adverse) associated with drug therapy. The bulk of the clinical literature that has been published about drug interactions has focused either on the mechanisms, pharmacokinetic studies, or cases observed by clinicians. However, when it comes to the true risk of a drug interaction, or the probability of such an interaction occurring in a given population, a dearth of information is available. This area is opportune for the application of epidemiological and outcomes-based studies.

Onychomycosis. Baseline results of an observational study.

The investigators present an analysis of baseline quality-of-life and patient-management approaches from an observational study of 150 patients being treated by podiatric physicians and dermatologists for onychomycosis. The majority (73%) made the initial office visit specifically because of their onychomycosis. Both men and women indicated that they had substantial physical discomfort as well as concerns related to appearance. Women reported significantly more problems than did men as a result of their onychomycosis. Physicians reported that 54% of patients suffered from toenail discomfort, 36% had pain while walking, 40% reported that their condition limited wearing of shoes, and 67% were embarrassed by the condition. The results of this study suggest that the treatment approach of podiatric physicians is more likely to address the palliative concerns of patients with onychomycosis, while the approach of dermatologists is more likely to attempt a definitive cure.

Cigarette smoking and clinically significant drug interactions.

OBJECTIVE: To review clinically significant drug interactions associated with cigarette smoking. DATA SOURCES: Data from scientific literature were identified by using a MEDLINE search. Data were extracted, evaluated, and summarized for this review. STUDY SELECTION: Findings and experiences were selected from clinical, epidemiologic, and pharmacokinetic studies; review articles; case studies; abstracts; letters to the editor, and proceedings. DATA EXTRACTION: Data from human studies published in English were evaluated. Only interactions deemed clinically significant are included in this review. Conclusions derived from review articles on the subject of smoking and drug interactions also were used. DATA SYNTHESIS: Cigarette smoking can affect drug therapy via pharmacokinetic and pharmacodynamic mechanisms. Pharmacokinetic drug interactions are presented for theophylline, tacrine, insulin, flecainide, propoxyphene, propranolol, diazepam, and chlordiazepoxide. Pharmacodynamic interactions are described for antihypertensive and antianginal agents, antilipidemics, oral contraceptives, and histamine2-receptor antagonists. CONCLUSIONS: Cigarette smoking can reduce the efficacy of certain drugs or make drug therapy more unpredictable. Pharmacokinetic interactions may cause smokers to require a larger dosage of certain drugs through an increase in plasma clearance, a decrease in absorption, an induction of cytochrome P450 enzymes, or a combination of these factors. Pharmacodynamic interactions may increase the risk of adverse events in smokers with cardiovascular or peptic ulcer disease, and in women who smoke and use oral contraceptives. Healthcare professionals should pay special attention to patients with these profiles and should try to prevent cigarette smoking or encourage patients to discontinue this addictive habit.