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Michael Benigno,1 Kathryn P Anastassopoulos,2 Arash Mostaghimi,3 Margarita Udall,1 Shoshana R Daniel,1 Joseph C Cappelleri,4 Pratibha Chander,1 Peter M Wahl,2 Jennifer Lapthorn,2 Laura Kauffman,2 Linda Chen,1 Elena Peeva5 1Pfizer Inc, New York, NY 10017, USA; 2Covance Market Access Services Inc, Gaithersburg, MD 20878, USA; 3Brigham & Women’s Hospital, Harvard University, Boston, MA 02115, USA; 4Pfizer Inc., Groton, CT 06340, USA; 5Pfizer Inc., Cambridge, MA 02139, USACorrespondence: Kathryn P AnastassopoulosCovance Market Access Services Inc., 9801 Washingtonian Blvd., 9th Floor, Gaithersburg, MD 20878, USATel +1240 632-3304Email Kathryn.Anastassopoulos@covance.comPurpose: Alopecia areata (AA) is an autoimmune disease characterized by the development of non-scarring alopecia. The prevalence is not well known, and estimates vary considerably with no recent estimates in the United States (US). The objective of this study was to define the current AA point prevalence estimate among the general population in the US overall and by severity.Patients and Methods: We administered an online, cross-sectional survey to a representative sample of the US population. Participants self-screening as positive for AA using the Alopecia Assessment Tool (ALTO) also completed the Severity of Alopecia Tool (SALT) to measure the severity of disease as a percent of scalp hair loss. Self-reported AA participants were invited to upload photographs for adjudication of AA by 3 clinicians.Results: The average age of participants was 43 years. Approximately half of the participants (49.2%) were male, and the majority were white (77.1%) and not of Hispanic origin (93.2%). Among the 511 self-reported AA participants, 104 (20.4%) uploaded photographs for clinician evaluation. Clinician-adjudicated point prevalence of AA was 0.21% (95% CI: 0.17%, 0.25%) overall, 0.12% (95% CI: 0.09%, 0.15%) for “mild” disease (≤ 50% SALT score), and 0.09% (95% CI: 0.06%, 0.11%) for “moderate to severe” disease (> 50% SALT score) with 0.04% (95% CI: 0.02%, 0.06%) for the alopecia totalis/alopecia universalis (100% SALT score) “moderate to severe” subgroup. The average SALT score was 44.4% overall, 8.8% for “mild”, and 93.4% for “moderate to severe”.Conclusion: This study suggests that the current AA prevalence in the US is similar to the upper estimates from the 1970s at approximately 0.21% (700,000 persons) with the current prevalence of “moderate to severe” disease at approximately 0.09% (300,000 persons). Given this prevalence and the substantial impact of AA on quality of life, the burden of AA within the US is considerable.Keywords: epidemiology, Alopecia Assessment Tool, Severity of Alopecia Tool, teledermatology

Stacey J Ackerman,1 Tyler Knight,2 Peter M Wahl,2 Charles P Cartwright3 1Covance Market Access Services Inc., San Diego, CA, USA; 2Covance Market Access Services Inc., Gaithersburg, MD, USA; 3Center for Esoteric Testing, Laboratory Corporation of America Holdings, Burlington, NC, USA Background: Vulvovaginitis (VV) is a common reason women seek medical attention in the USA. Both the non-specific clinical presentation and risk of preterm labor or delivery necessitate accurate identification of the causative agents to guide appropriate therapy. The diagnostic accuracy of amplified molecular probe testing (AMP) has been shown to exceed that of non-amplified molecular probe (NAMP) by 20%–25%.Objective: To evaluate the impact of diagnosis with AMP testing on health care utilization, direct costs, and health outcomes, compared with NAMP, for symptomatic patients with suspected VV from a commercial payer perspective. Methods: Symptomatic women (aged 18–64 years) who underwent VV testing with AMP or NAMP from January 1, 2012–December 31, 2016 were identified using the Truven Health Analytics MarketScan Database; those with continuous medical and pharmacy benefit enrollment 6 months pre/post AMP or NAMP testing were included. Patients were propensity score (PS) matched and 6-month all-cause health care resource utilization, all-cause direct costs (2017 USD), risk of all-cause hospitalization, and risk of preterm labor or delivery were compared between cohorts. Results: After PS match (N=46,810 per group, mean age 34.2 years), AMP had significantly (all P

Background: Several efforts are under way to develop and test methods for prospective drug safety monitoring using large, electronic claims databases. Prospective monitoring systems must incorporate signalling algorithms and techniques to mitigate confounding in order to minimize false positive and false negative signals due to chance and bias.Objective: The aim of the study was to describe a prototypical targeted active safety monitoring system and apply the framework to three empirical examples.Methods: We performed sequential, targeted safety monitoring in three known drug/adverse event (AE) pairs: (i) paroxetine/upper gastrointestinal (UGI) bleed; (ii) lisinopril/angioedema; (iii) ciprofloxacin/Achilles tendon rupture (ATR). Data on new users of the drugs of interest were extracted from the HealthCore Integrated Research Database. New users were matched by propensity score to new users of comparator drugs in each example. Analyses were conducted sequentially to emulate prospective monitoring. Two signalling rules--a maximum sequential probability ratio test and an effect estimate-based approach--were applied to sequential, matched cohorts to identify signals within the system.Results: Signals were identified for all three examples: paroxetine/UGI bleed in the seventh monitoring cycle, within 2 calendar years of sequential data; lisinopril/angioedema in the second cycle, within the first monitoring year; ciprofloxacin/ATR in the tenth cycle, within the fifth year.Conclusion: In this proof of concept, our targeted, active monitoring system provides an alternative to systems currently in the literature. Our system employs a sequential, propensity score-matched framework and signalling rules for prospective drug safety monitoring and identified signals for all three adverse drug reactions evaluated. [ABSTRACT FROM AUTHOR]

In the United States, demand for total hip arthroplasty (THA) and THA revision procedures are increasing due to an aging population, a longer life expectancy, and an increasing prevalence of osteoarthritis. This retrospective cohort study identified patients 65 years and older in the Medicare 5% Standard Analytic Files who underwent THA for osteoarthritis between January 1, 2009, and September 30, 2010. The authors estimated the 5-year cumulative revision risk (CRR) using the Kaplan-Meier method, revision-related complications, and Medicare expenditures. Using a 6.22% compound annual growth rate from the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality, the authors estimated the number of THAs that will be performed from 2018 to 2027 and calculated the 10-year projected savings to Medicare for a 1% reduction in CRR. Among 7820 patients, the mean age was 74.4 years, and 62.4% were female. Cumulative revision risk was 4.2% at 5 years (through September 30, 2015), with 30.8% of revisions occurring within 90 days of the THA. At least 24.4% of revision patients had a complication. Median revision inpatient stay and episode of care (through 90 days) expenditures were $23,847 and $36,157, respectively. With a 1% absolute reduction in CRR, Medicare could save $697 million over a 10-year period, or $985 million when including Medicare Advantage, which represented 29.2% of 2016 Medicare payments. Strategies to reduce the risk of THA revision, such as the use of implant constructs with lower CRR and value-based payment models, are needed to achieve Medicare payment reductions while maintaining or improving quality of care for Medicare beneficiaries. [Orthopedics. 2019; 42(1):e86-e92.]., (Copyright 2018, SLACK Incorporated.)

We conducted a cohort study of acute, noninfectious liver injury among oral antimicrobial users. Potential cases were identified in the HealthCore Integrated Research Database (HIRD(SM)) population between July 1, 2001, and March 31, 2009, using ICD-9-CM codes primarily for acute and subacute necrosis of the liver, hepatic coma, and unspecified hepatitis. Liver test results were used to confirm case status according to published criteria. Two physician reviewers experienced in studying acute liver injury (blinded to study drug exposures) evaluated data abstracted from hospital and emergency department records to validate potential cases. Of 715 potential cases having claims associated with any of the primary screening codes, 312 (44%) were valid cases, 108 (15%) were not cases, and 295 (41%) were of uncertain status (records inadequate for validation). Among potential cases with adequate medical records, the PPV for presence of any of the primary codes was 74% (95% CI, 70%-78%). The highest PPV for a single code was for acute and subacute necrosis of the liver (84%; 95% CI, 77%-90%). Evaluation of cases of noninfectious liver injury using hospital and emergency department medical records continues to represent the preferred approach in studies using insurance claims data.

Study Objective: To estimate the incidence and relative risk of a hospitalization or emergency visit for noninfectious liver injury in users of eight oral antimicrobials-amoxicillin, amoxicillin-clavulanic acid, clarithromycin, cefuroxime, doxycycline, levofloxacin, moxifloxacin, telithromycin-compared with nonusers of these antimicrobials., Design: Retrospective, observational cohort study with a nested case-control analysis., Data Source: HealthCore Integrated Research Database., Patients: Adults with continuous health plan enrollment for at least 6 months before study entry who had a new dispensing of a study antimicrobial between July 1, 2001, and March 31, 2009. Cases had diagnoses indicating noninfectious liver injury during follow-up. To control for potentially confounding risk factors, 10 controls at risk for liver injury during follow-up were matched to each case by age, sex, and event date (liver injury date of the case), and analyses were adjusted for medical history, concomitant drugs, and health care service use., Measurements and Main Results: Two physician reviewers (blind to exposure) validated the cases. Among 1.3 million antimicrobial users, we identified 607 cases of liver injury, including 82 cases of severe hepatocellular injury and 11 cases of liver failure. Liver injury incidence in nonusers of study antimicrobials was 35/100,000 person-years (95% confidence interval [CI] 29-42/100,000 person-years). For valid cases, the adjusted relative risk among current users of multiple antimicrobials was 3.2 (95% CI 1.6-6.7). Levofloxacin had the highest relative risk for current single use (3.2, 95% CI 1.8-5.8). Relative risks were also elevated for amoxicillin-clavulanic acid (2.5, 95% CI 1.3-5.0), doxycycline (2.5, 95% CI 1.2-5.2), moxifloxacin (2.3, 95% CI 1.1-4.7), and amoxicillin (2.3, 95% CI 1.1-4.7)., Conclusion: The results support a comparatively high adjusted relative risk of liver injury among patients exposed concurrently to multiple antimicrobials and modest elevations in the risk for several antimicrobials used alone; however, we found little evidence of any strong effect of commonly used antimicrobials on the risk of liver injury., (© 2013 RTI Health Solutions. Pharmacotherapy published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacy.)

Background: Older-generation anticonvulsants that highly induce cytochrome P450 enzyme system activity produce metabolic abnormalities that may increase cardiovascular risk. The objective of this study was to evaluate the risk of ischemic cerebrovascular and coronary events in adult new users of anticonvulsants that highly induce cytochrome P450 activity compared with other anticonvulsant agents, as observed in a routine care setting., Methods and Results: This was a cohort study of patients 40 to 64 years old from the HealthCore Integrated Research Database who had initiated an anticonvulsant medication between 2001 and 2006 and had no recorded major coronary or cerebrovascular condition in the 6 months before treatment initiation. Propensity score (PS) matching was used to evaluate ischemic cerebrovascular and coronary risk among anticonvulsant new users. High-dimensional propensity score (hdPS)-matched analyses were used to confirm adjusted findings. The study identified 913 events in 166 031 unmatched new treatment episodes with anticonvulsant drugs. In a PS-matched population of 22 864 treatment episodes, the rate ratio (RR) for ischemic coronary or cerebrovascular events associated with highly inducing agents versus other agents was 1.22 (95% CI, 0.90-1.65). The RR moved to 0.99 (95% CI, 0.73-1.33) with adjustment for hdPS matching (RR, 1.47; 95% CI, 0.95-2.28 for cerebrovascular events; RR, 0.70; 95% CI, 0.47-1.05 for coronary events)., Conclusions: In this exploratory analysis, there was no evidence of a consistent and statistically significant effect of initiating anticonvulsants that highly induce cytochrome P450 activity on ischemic coronary or cerebrovascular outcomes compared with other agents, given routine care utilization patterns.

Background: Health insurance claims databases can provide data for studies of vaccine-related Guillain-Barre' Syndrome (GBS), but not all patients with a diagnostic ICD-9-CM code for GBS have the disease. The objective of this study was to evaluate the positive predictive values (PPVs) of claims-based algorithms for identifying GBS cases in 4 claims database environments., Methods: Potential cases were adolescents ages 11-21 with at least one claim for GBS (ICD-9-CM code 357.0). Medical record reviews by a panel of 3 neurologists were conducted for case confirmation. Claims data considered for inclusion in the case-ascertainment algorithm included coding position, physician specialty, visit type, diagnostic tests. PPVs were used to assess the contribution of study factors in predicting case status., Results: Among 361 individuals with a GBS diagnosis code, 106 were confirmed overall (PPV=0.29), varying from 0.24 to 0.56 across the 4 sites. Requiring the GBS code to be associated with a neurologist visit (PPV=0.53) or to be in a primary position on an inpatient claim (0.56) improved the performance. A composite algorithm including a primary inpatient GBS code and a neurologist visit associated with any GBS code gave the highest PPV (0.70). Incorporating claims for diagnostic testing had little impact on the PPV. Findings were generally similar across study sites., Conclusions: Algorithms were able to identify GBS cases better than the single occurrence of the diagnostic code for GBS, and these algorithms may perform similarly in different claims environments., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: A new meningococcal conjugate vaccine (MCV4) was introduced in 2005. Shortly after, case reports of Guillain-Barré syndrome (GBS), a serious demyelinating disease, began to be reported to the Vaccine Adverse Event Reporting System. In 2006, the Centers for Disease Control and Prevention and the Food and Drug Administration requested the evaluation of GBS risk after MCV4 vaccination. We conducted a study to assess the risk of GBS after MCV4 vaccination using health plan administrative and claims data together with the review of primary medical records of potential cases., Methods: Retrospective cohort study among 12.6 million 11- to 21-year-old members of five US health plans with a total membership of 50 million. Automated enrollment and medical claims data from March 2005 through August 2008 were used to identify the population, the vaccinations administered, and the medical services associated with possible GBS. Medical records were reviewed and adjudicated by a neurologist panel to confirm cases of GBS. The study used distributed data analysis methods that minimized sharing of protected health information., Results: We confirmed 99 GBS cases during 18,322,800 person-years (5.4/1,000,000 person-years). More than 1.4 million MCV4 vaccinations were observed. No confirmed cases of GBS occurred within 6 weeks after vaccination. The upper 95% CI for the attributable risk of GBS associated with MCV4 is estimated as 1.5 cases per 1,000,000 doses., Conclusions: Among members of five US health plans, MCV4 vaccination was not associated with increased GBS risk., (Copyright © 2012 John Wiley & Sons, Ltd.)

PURPOSE: To validate the administrative claims identification of a diagnosis of Stevens-Johnson syndrome (SJS) using medical records as the "gold standard" in a large, commercially insured US population. METHODS: Patients with >1 medical claim with the International Classification of Diseases, Ninth Revision, Clinical Modification code 695.1x between 1 July 2000 and 31 May 2007 were queried in the HealthCore Integrated Research Database(SM) , which contains administrative claims data for 14 commercial health insurance plans. Trained nurses and pharmacists abstracted pertinent information from the identified patients' medical records, which were then reviewed by two independent dermatologists to identify criteria to determine SJS diagnosis. Positive predictive values (PPVs) based on the claims and chart data were computed for all the cases. RESULTS: Medical charts for 200 claims-identified cases, with the International Classification of Diseases, Ninth Revision, Clinical Modification code 695.1x, were abstracted and reviewed by the dermatologists. A total of five cases (PPV = 2.50%, 95%CI = 0.8%-5.7%) were determined to be SJS with clinical certainty. PPVs varied with data stratification: PPV for inpatient claims only (PPV = 2.00%, 95%CI = 0.24%-7.04%), inpatient claims with 695.1x in first diagnosis field (PPV = 4.11%, 95%CI = 0.86%-11.54%), and final decisions of either clinical certainty or probable cases of SJS (PPV = 6.00%, 95%CI = 3.14%-10.25%). CONCLUSION: These findings demonstrate the difficulties associated with identifying rare disorders, which lack specific diagnostic criteria, within administrative claims databases. They underscore the challenges of using claims data to monitor ill-defined clinical conditions as well as the need to validate claims-identified cases with information from other sources, such as medical charts. Copyright © 2012 John Wiley & Sons, Ltd., (Copyright © 2012 John Wiley & Sons, Ltd.)

The Post-Licensure Rapid Immunization Safety Monitoring (PRISM) system is a cohort-based active surveillance network initiated by the US Department of Health and Human Services to supplement preexisting and other vaccine safety monitoring systems in tracking the safety of monovalent pandemic 2009 H1N1 influenza vaccine in the United States during 2009-2010. PRISM investigators conducted retrospective analysis to determine whether 2009 H1N1 vaccination was associated with increased risk of any of 14 prespecified outcomes. Five health insurance and associated companies with 38 million members and 9 state/city immunization registries contributed records on more than 2.6 million doses of 2009 H1N1 vaccine. Data on outcomes came from insurance claims. Complementary designs (self-controlled risk interval, case-centered, and current-vs.-historical comparison) were used to optimize control for confounding and statistical power. The self-controlled risk interval analysis of chart-confirmed Guillain-Barré syndrome found an elevated but not statistically significant incidence rate ratio following receipt of inactivated 2009 H1N1 vaccine (incidence rate ratio = 2.50, 95% confidence interval: 0.42, 15.0) and no cases following live attenuated 2009 H1N1 vaccine. The study did not control for infection prior to Guillain-Barré syndrome, which may have been a confounder. The risks of other health outcomes of interest were generally not significantly elevated after 2009 H1N1 vaccination.

Purpose: Proton pump inhibitors (PPIs) and corticosteroids are commonly prescribed drugs; however, each has been associated with fracture and community-acquired pneumonia. How physicians select patients for co-therapy may have implications for potential additive or synergistic toxicities., Methods: We conducted a retrospective cohort study of 13 749 incident corticosteroid users with no prior PPI exposure using the HealthCore Integrated Research Database(SM) . We used logistic regression to evaluate the association between PPI initiation in the first 30 days of steroid therapy and corticosteroid dose, clinical risk factors including comorbid diseases, and medication use including prescription nonsteroidal anti-inflammatory drugs (NSAIDs)., Results: A new PPI prescription within 30 days of starting corticosteroids was filled by 1050 patients (7.6%). PPI use was associated with the number of baseline comorbid conditions (OR = 1.21 for each additional condition, 95%CI = 1.13-1.28), recent hospitalization (OR = 4.71, 95%CI = 4.02-5.52), prednisone dose higher than 40 mg/day (OR = 1.87, 95%CI = 1.45-2.41), history of gastroesophageal reflux or gastric ulcer disease (OR = 1.54, 95%CI = 1.24-1.91), renal insufficiency (OR = 2.06, 95%CI = 1.73-2.46), and liver disease (OR = 1.82, 95%CI = 1.45-2.28). The concomitant use of prescription NSAIDs was also associated with PPI use (OR = 1.89, 95%CI = 1.32-2.70); however, the total use of PPIs in this group was low (6.3%, 95%CI = 4.4-8.2%)., Conclusions: Overall, PPI therapy among corticosteroid users was uncommon, even among those with risk factors for gastrointestinal toxicity. PPI use was significantly more common among patients who had recently been hospitalized, had a greater burden of comorbid illness, or were receiving high daily doses of corticosteroids., (Copyright © 2012 John Wiley & Sons, Ltd.)

It was the purpose of the present study to validate administrative claims codes for idiopathic thrombotic thrombocytopenic purpura (TTP) in a commercially-insured US population. Patients with at least one medical claim with ICD-9 code 446.6X between 1/1/2001 and 5/31/2008 were identified in the HealthCore Integrated Research Database (HIRD). A chart abstraction form was developed to enable case determination for patients identified by the claims code. Two clinical experts, not involved in the design of the study, reviewed the abstracted medical record data and determined whether definite evidence supporting the diagnosis of TTP was present. The positive predictive value (PPV) of the claims coding algorithm for cases assessed by both reviewers was computed. The claims algorithm was further refined and the PPV of the refined algorithm was computed. One hundred eighty-nine abstracted charts were reviewed by two clinical experts; 86 were assessed to have definite evidence supporting the diagnosis of TTP (PPV 45.5% [86/189; 95% confidence interval (CI), 38.3-52.9%]). Refinement of the claims algorithm first included the use of plasma exchange treatment, resulting in 103 potential cases, of which 67 were assessed to have definite evidence supporting the diagnosis of TTP (PPV 65.0%; 95% CI, 55.0-74.2%). Further refinement of the claims algorithm ruled out alternative diagnoses that may mimic TTP; 34 were assessed to have definite evidence supporting the diagnosis of TTP (PPV 72.3% [34/47; 95% CI, 57.4-84.4%]).Our findings demonstrate the difficulty of confirming the diagnosis of rare disorders that lack definite diagnostic criteria, and indicate that more complex claims coding algorithms are necessary for identifying these disorders.

Purpose: To validate administrative claims codes with medical chart review for myocardial infarction (MI), ischemic stroke, and severe upper gastrointestinal (UGI) bleed events in a large, commercially-insured US population., Methods: These validation studies were part of a larger study examining the risk of MI, ischemic stroke, and severe UGI bleeds in patients receiving a new prescription of selective cyclooxygenase (COX)-2 inhibitors (coxibs) and non-over-the-counter (OTC) non-steroidal anti-inflammatory drugs (NSAIDs), between 1 July 2002 and 30 September 2004. Patients from the study cohort and other health plan members from the HealthCore Integrated Research Database(SM) (HIRD) experiencing these events were selected for these studies. The positive predictive value (PPV) of each of the claims code algorithms, using medical chart review as the gold standard, was calculated., Results: Two hundred charts per event were abstracted. The PPV for MI was 88.4% (177/200; 95%CI, 83.2-92.5%); PPV for ischemic stroke was 87.4% (175/200; 95%CI, 82.0-91.7%); PPV for severe UGI bleed was 56.5% (109/193; 95%CI, 49.2-63.6%). Refining the ischemic stroke claims algorithm resulted in a PPV of 95.5% (95%CI, 91.0-98.2%); refining the claims algorithm for severe UGI bleed resulted in a PPV of 87.8% (95%CI, 78.7-94.0%)., Conclusion: The results suggest that, for certain adverse events, claims data can serve as the basis for pharmacoepidemiology research and drug safety surveillance in the US.

Context: In 2008, the US Food and Drug Administration mandated warning labeling for anticonvulsant medications regarding the increased risk of suicidal thoughts and behaviors. The decision was based on a meta-analysis not sufficiently large to investigate individual drugs., Objective: To evaluate the risk of suicidal acts and combined suicidal acts or violent death associated with individual anticonvulsants., Design: A cohort study of the risk of suicidal acts and combined suicidal acts or violent death in patients beginning use of anticonvulsant medications compared with patients initiating a reference anticonvulsant drug., Setting and Patients: Patients 15 years and older from the HealthCore Integrated Research Database (HIRD) who began taking an anticonvulsant between July 2001 and December 2006., Main Outcome Measures: Cox proportional hazards models and propensity score-matched analyses were used to evaluate risk of attempted or completed suicide and combined suicidal acts or violent death, controlling for psychiatric comorbidities and other risk factors, among individual anticonvulsants compared with topiramate and secondarily carbamazepine., Results: The study identified 26 completed suicides, 801 attempted suicides, and 41 violent deaths in 297,620 new episodes of treatment with an anticonvulsant (overall median follow-up, 60 days). The incidence of the composite outcomes of completed suicides, attempted suicides, and violent deaths for anticonvulsants used in at least 100 treatment episodes ranged from 6.2 per 1000 person-years for primidone to 34.3 per 1000 person-years for oxcarbazepine. The risk of suicidal acts was increased for gabapentin (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.11-1.80), lamotrigine (HR, 1.84; 95% CI, 1.43-2.37), oxcarbazepine (HR, 2.07; 95% CI, 1.52-2.80), tiagabine (HR, 2.41; 95% CI, 1.65-3.52), and valproate (HR, 1.65; 95% CI, 1.25-2.19), compared with topiramate. The analyses including violent death produced similar results. Gabapentin users had increased risk in subgroups of younger and older patients, patients with mood disorders, and patients with epilepsy or seizure when compared with carbamazepine., Conclusion: This exploratory analysis suggests that the use of gabapentin, lamotrigine, oxcarbazepine, and tiagabine, compared with the use of topiramate, may be associated with an increased risk of suicidal acts or violent deaths.

Background: Relationships between long-term use and level of dual antiplatelet therapy and outcomes after drug-eluting stent implantation are not well established., Methods: This is a retrospective cohort study of 9,256 patients receiving drug-eluting stents between January 2003 and August 2006. We classified patients according to tertiles of clopidogrel use during the 12 months after stent implantation. We used inverse probability weighting to account for differential selection into levels of clopidogrel use and logistic regression to estimate propensity scores for levels of clopidogrel use. We used Cox proportional hazards models to estimate effects of level of clopidogrel use on risk of bleeding events, death, and death or nonfatal myocardial infarction., Results: There were 3,102 patients in the high-use group, 3,069 in the medium-use group, and 3,085 in the low-use group. Compared with the high-use group, risk of death or nonfatal myocardial infarction was greater in the medium-use group (hazard ratio [HR] 1.46, 95% CI 1.09-1.99, P = .01) and the low-use group (HR 1.59, 95% CI 1.18-2.14, P = .002). The risk of bleeding events was lower in the medium-use group (HR 0.84, 95% CI 0.71-0.98, P = .03) and the low-use group (HR 0.77, 95% CI 0.65-0.90, P = .002)., Conclusions: Higher clopidogrel use 12 months after drug-eluting stent implantation was associated with a greater risk of subsequent bleeding events. Lower use was associated with a greater risk of death or nonfatal myocardial infarction.

Objective: To examine the association of Alzheimer's disease (AD) with common chronic conditions, acute care events, and risk of hospitalization., Study Design: Retrospective matched cohort analysis., Methods: Community-dwelling subjects with a diagnosis of and/or medication for AD were matched to subjects without AD based on age, sex, and geographic region. Administrative claims from commercially insured health plans for medical and pharmacy services provided from January 1, 2000, to March 31, 2006 (inclusive) were analyzed. The Deyo Charlson Index (DCI) was used to assess the number of chronic conditions. The outcomes of interest were risk of fractures and hospitalization., Results: Among 5396 persons with AD and a matched cohort of 5396 persons without the condition, subjects with AD were more likely to have a diagnosis for any of the DCI components, had a higher rate of fractures (17.7% vs 7.9%, P <.00) and other urgent medical events (eg, pneumonia 14.0% vs 6.3%, P <.00), and were more likely to be hospitalized (odds ratio = 1.7; 95% confidence interval = 1.5, 1.9). There were significant differences in the medication use between the 2 groups, with the use of psychotics/tranquilizers 9-fold higher among persons with AD., Conclusion: Persons with AD have higher odds of experiencing a fracture, being hospitalized, and requiring other acute care medical services than those without AD. The disease also is associated with a higher prevalence of common chronic conditions.

Background: Lymphatic mapping and sentinel lymphadenectomy (LM/SL) provide important prognostic information for patients with early-stage melanoma. Although the use of this technique in patients with thin melanomas (< or =1.00 mm) is not routine, risk factors that may predict sentinel lymph node (SLN) positivity in this patient population are under investigation. We sought to determine whether mitotic rate (MR) is associated with SLN positivity in thin-melanoma patients and, therefore, whether it may be used to risk-stratify and select patients for LM/SL., Methods: Clinical and histopathologic variables were reviewed for 181 patients with thin melanomas who underwent LM/SL from January 1996 through January 2004. Univariate and multivariate logistic regression analyses were performed to identify factors associated with SLN positivity. Risk groups were defined on the basis of the development of a classification tree., Results: The overall SLN positivity rate was 5%. All patients with positive SLNs had an MR of >0. By univariate analysis, MR and thickness were significant predictors of SLN positivity. The association between MR and SLN positivity remained significant controlling for each of the other variables evaluated. On the basis of a classification tree, patients with an MR >0 and tumor thickness > or =.76 mm were identified as a higher-risk group, with an SLN positivity rate of 12.3%., Conclusions: In patients with thin melanomas, MR >0 seems to be a significant predictor of SLN positivity that may be used to risk-stratify and select patients for LM/SL. To confirm these results, the predictive value of MR for SLN positivity needs to be validated in other populations of thin-melanoma patients.

Background: Non-small cell carcinoma of the lung invading the pulmonary artery (PA) has traditionally been treated by pneumonectomy. Although PA resection and reconstruction (PAR) has begun to gain acceptance, previous series of PAR by the simplest technique of tangential excision and primary repair have been unfavorable. We have maintained a policy of performing PAR preferentially whenever anatomically feasible, and usually this has been possible by tangential excision and primary repair. This study sought to determine if this approach is sound., Methods: Retrospective clinical and pathologic review., Results: Thirty-three PARs were performed from 1992 to 1999. The patients, followed 6 to 65 months (mean 25), were aged 36 to 80 years (mean 61), and their tumors were pathologic stage IB (n = 7), IIB (n = 13), IIIA (n = 9), and IIIB (n = 4). The mean preoperative forced expiratory volume in 1 second was 70% predicted. The procedures included 14 bronchial sleeve lobectomies with PAR and 19 simple lobectomies with PAR. The PARs were performed without heparinization and included 19 tangential excisions with primary closure, 11 larger tangential excisions with pericardial patch closure, and 3 sleeve resections. There were no operative deaths and 2 (6.1%) early major complications, all unrelated to the PAR. Thirteen patients (39%) had early minor complications. Four-year Kaplan-Meier survival was 48.3% for stages I/II and 45% for stage III. Ipsilateral, central, intrathoracic recurrence occurred in 3 patients (9.1%)., Conclusions: These data are not dramatically different from those reported for standard resections. Although the numbers are small, the results suggest that lobectomy with PAR by tangential excision is an acceptable alternative to pneumonectomy whenever anatomically possible.

Study Objectives: To compare short-term functional outcomes following unilateral and bilateral lung volume reduction surgery (LVRS) performed in patients with advanced emphysema., Methods: LVRS was performed unilaterally in 32 patients and bilaterally in 119 patients. Pulmonary function testing and 6-min walk test (6MWT) were performed preoperatively and repeated at 3 to 6 months postoperatively., Results: Bilateral LVRS was associated with increased in-hospital mortality (10% vs 0%, p<0.05) and a higher incidence of postoperative respiratory failure (12.6% vs 0%; p<0.05) compared with unilateral LVRS. There was no significant difference in duration of air leaks between unilateral and bilateral groups, but the mean hospital stay was significantly longer following bilateral LVRS (21.1+/-32.0 days vs 14.2+/-14.0 days; p<0.05). Preoperatively, there was no significant difference between the unilateral and bilateral groups with respect to FEV1, FVC, residual volume, or 6MWT distance. However, for all of these parameters, the magnitude of improvement was significantly greater following bilateral LVRS. Notably, the magnitude of improvement in each parameter following unilateral LVRS exceeded half that following bilateral LVRS, suggesting that functional outcomes after the unilateral procedure were disproportionate to the amount of tissue resected. Serial functional assessment of seven patients undergoing staged unilateral procedures (two unilateral procedures separated in time by at least 3 months) demonstrated somewhat unpredictable responses; failure to achieve a favorable response to the initial procedure did not necessarily portend a similar outcome with the contralateral side, and vise versa., Conclusions: Bilateral LVRS produces a greater magnitude of short-term functional improvement than does the unilateral procedure and should be considered the procedure of choice for most patients. Unilateral LVRS should be reserved for patients in whom factors contraindicating entrance into one hemithorax exist.

Background: End-stage chronic obstructive pulmonary disease has traditionally been treated with lung transplantation. For 2 years, our lung transplantation program has placed patients with appropriate criteria for lung transplantation and volume reduction into a prospective management algorithm. These patients are offered the lung volume reduction option as a "bridge" to "extend" the eventual time to transplantation. We examine the results of this pilot program., Methods: From October 11, 1993, to April 17, 1997, 31 patients were evaluated for lung transplantation who also had physiologic criteria for volume reduction (forced expiratory volume in 1 second < or = 25%; residual volume > 200%; significant ventilation/perfusion heterogeneity). All patients completed 6 weeks of pulmonary rehabilitation and then had baseline pulmonary function and 6-minute walk tests. These patients were then offered volume reduction as a "bridge" and were simultaneously listed for transplantation. Postoperatively, these 31 patients were then divided into two groups: Those with satisfactory results at 4 to 6 months after volume reduction and those with unsatisfactory results. Volume reduction was performed through a video thoracic approach in 87% of the patients and bilateral median sternotomy in the remaining 13%. The condition of the patients was monitored after the operation with repeated pulmonary function tests and 6-minute walk tests at 3-month intervals., Results: Twenty-four of 31 patients (77.4%) had primary success (at 4 to 6 months) results after lung volume reduction and 7 patients (22.6%) had primary failure, including 1 patient who died in the perioperative period (3.2%). Four patients (16.7%) from the primary success cohort had significant deterioration in their pulmonary function during intermediate-term follow-up and were then reconsidered for lung transplantation. Two of them have subsequently undergone transplantation with good postoperative pulmonary function results. Interestingly, three patients had alpha 1-antitrypsin deficiency; two had a poor outcome of lung volume reduction and primary failure., Conclusions: Lung volume reduction in these patients is safe. Seventy-seven percent of otherwise suitable candidates for lung transplantation achieved initial good results from volume reduction and were deactivated from the list (placed on status 7). Most patients entering our prospective management algorithm have either significantly delayed or completely avoided lung transplantation after volume reduction. Lung volume reduction has substantially affected the practice, timing, and selection of patients for lung transplantation. Our waiting list now has a reduced percentage of patients with a diagnosis of chronic obstructive pulmonary disease compared with 3 years ago. Our experience suggests that lung volume reduction may be limited as a "bridge" in alpha 1-antitrypsin deficiency.

Objective: Traditionally, despite ventilation/perfusion mismatch, single lung transplantation has been the mainstay for end-stage chronic obstructive pulmonary disease. We tested the hypothesis that bilateral sequential lung transplantation has better short- and intermediate-term results than single lung transplantation for chronic obstructive pulmonary disease., Methods: One hundred twenty-six consecutive lung transplants have been performed from November 1991 to March 1996. Seventy-six have been for chronic obstructive pulmonary disease. The diagnosis of this disease includes emphysema (80.3%), alpha 1-antitrypsin deficiency (9.2%), lymphangioleiomyomatosis (7.9%), and obliterative bronchiolitis (2.6%). Twenty-nine transplants have been bilateral and 47 have been single. Mean age was 55.3 for patients having single lung transplantation and 48.8 for those having bilateral lung transplantation (p = 0.001). The distribution of the diagnoses was similar between the two groups. At 6 months, there were 29 survivors of single lung transplantation and 20 survivors of bilateral lung transplantation, with complete data for evaluation. Pulmonary function tests and 6-minute walk tests were evaluated at a mean of 15.4 and 12.8 months after transplantation, respectively., Results: Sixty-day mortality was 21.3% for single lung transplantation versus only 3.45% for bilateral lung transplantation (p = 0.03). Additionally, Kaplan-Meier analysis revealed 1- and 2-year survivals of 71.1% and 63.3% for single lung transplantation versus 90% and 90% for bilateral lung transplantation, respectively. Multiple major morbidities were analyzed. Primary graft failure was significantly reduced in the bilateral group (p = 0.049). Both 6-minute walk tests and forced expiratory volume in 1 second were improved from baseline by both single and bilateral lung transplantation (p = 0.001)., Conclusions: Bilateral lung transplantation improves forced expiratory volume in 1 second and 6-minute walk tests significantly over single lung transplantation (p < 0.0001). Both perioperative mortality and Kaplan-Meier survival (to 3 years) are significantly improved when bilateral rather than single lung transplantation is used for chronic obstructive pulmonary disease in our series (p < 0.05). This is probably the result of significantly reduced primary graft failure.

Study Objectives: To compare short-term outcomes following bilateral lung volume reduction surgery performed by median sternotomy (MS) and video-assisted thoracoscopic surgery (VATS)., Methods: Bilateral lung volume reduction surgery was performed by MS in 80 patients and by VATS in 40. All patients underwent preoperative assessment with pulmonary function testing, arterial blood gas determination, and 6-min walk test (6MWT). Pulmonary function testing and 6MWT were repeated at 3 to 6 months postoperatively., Results: The mean age of the VATS group was lower than that of the MS group (59.3 +/- 9.4 vs 62.4 +/- 6.9 years; p = 0.001), but there were no differences in baseline functional parameters of disease severity (FEV1, FVC, residual volume [RV], arterial PCO2, or 6MWT). All patients in both groups were extubated at the completion of surgery, but 17.5% of patients in the MS group and 2.5% in the VATS group (p = 0.02) subsequently required reintubation at some point during the postoperative course. Thirty-day operative mortality was 4.2% for the MS group and 2.5% for the VATS group (p = not significant). However, total in-hospital mortality was 13.8% for the MS group, while it remained 2.5% for the VATS group (p = 0.05). Mortality was largely confined to patients 65 years of age or older. There was no significant difference in duration of air leaks or length of hospital stay between the two groups. Functional outcomes achieved with the two techniques were similar. Specifically, there was no difference between the two groups in mean postoperative FEV1, FVC, RV, or 6MWT, or in the magnitude of change in these parameters over preoperative values., Conclusions: Bilateral lung volume reduction surgery performed by either MS and VATS approaches leads to similar improvements in pulmonary function and exercise tolerance. VATS is associated with a significantly lower incidence of respiratory failure and a trend toward decreased in-hospital mortality and may be the preferred technique, particularly for high-risk patients.

Background: Cerebral circulation during urgent repair of acute type A aortic dissection has traditionally been managed with cardiopulmonary bypass and aortic cross clamping proximal to the innominate artery or by the use of hypothermic circulatory arrest (HCA). The more recently introduced retrograde cerebral perfusion (RCP) may confer additional cerebral protection during elective aortic arch reconstruction. The purpose of this study was to demonstrate the efficacy of RCP in the urgent repair of acute type A aortic dissection., Methods and Results: We evaluated 60 consecutive patients who underwent repair of acute type A aortic dissection over a 6-year period. Patients were grouped according to intraoperative circulatory management strategies. Group 1 consisted of 41 patients operated on early in the series who were managed by cardiopulmonary bypass and standard aortic cross clamping (n = 21) with conversion to HCA (n = 20) if the intimal tear extended into the aortic arch. Since 1993, 19 patients, who make up group 2, were managed with routine open distal anastomosis and HCA with RCP. Data were analyzed for clinically evident, radiographically confirmed cerebrovascular accidents and 60-day mortality and evaluated by chi 2 analysis. Stroke and mortality rates of patients managed with either cardiopulmonary bypass or HCA were 26.3% and 29.3%, respectively. Patients undergoing RCP experienced statistically significant reductions in rates of confirmed cerebrovascular accidents (0%, P = .015) and mortality (5.3%, P = .04)., Conclusions: We conclude that the introduction of circulatory management using RCP with HCA during urgent operative repair of acute type A aortic dissection has significantly improved both stroke and mortality rates.