Clay P. Wiske

Options to Promote Competitive Generics Markets in the United States

In August, the price of the 62-year-old drug pyrimethamine (Daraprim), used to treat many potentially fatal parasitic infections, was increased practically overnight from

Comparing the efficacy of shunting approaches and cerebral monitoring during carotid endarterectomy using a national database

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Physician Specialty Influences Care of Pelvic Inflammatory Disease

750 per tablet. This colossal increase attracted renewed attention to generic pharmaceutical price spikes, prompting public outrage and a new round of proposals to address this issue. Over the past few years, increasing drug shortages and price spikes have affected generic drugs, which now account for 86% of prescriptions and 29% of pharmaceutical spending.1 A stable supply of affordable generic pharmaceuticals is crucial to improve health care access and appropriate utilization for many Americans. A 2014 report from the US Government Accountability Office found that the number of active drug shortages increased steadily from 154 in 2007 to 456 in 2012, and the majority of the affected drugs were generic.2 According to a recent Senate subcommittee investigation, many generic drugs prices have increased substantially as producers have left the market; for example, the price of albuterol sulfate tablets, used for asthma and other lung diseases, increased 4014% between October 2013 and April 2014 from

Ruptured Pseudoaneurysm of the Dorsalis Pedis Artery Following Ankle Arthroscopy

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Practice Patterns of Fenestrated Aortic Aneurysm Repair: Nationwide Comparison of Z-Fen Adoption at Academic and Community Centers Since Commercial Availability:

434.3 These generic drug shortages and price spikes are adverse outcomes of a malfunctioning marketplace. Two features of the US generic drug market make it more prone to price swings and shortages than other commodity markets. First, entry into the generic drug market is restricted, including financial barriers (the cost of product formulation, quality assurance, and bioequivalence testing) and a time barrier due to the need for abbreviated clinical testing and the uncertainty of the Abbreviated New Drug Application (ANDA) review cycle. Second, again in contrast to more efficient commodity markets, there are barriers to the substitution of other products for a given generic drug molecule. The economics of the generic drug market are driven by the opportunity for 180 days of market exclusivity for the first generic product on the market. These products are available at prices only slightly reduced from those of the originator products. Generic manufacturers may enter the market after 180 days in the hope of a substantial financial return in the short period of time before the price of the product declines. Firms take a calculated risk in financing bioequivalence studies and in entering the marketplace without knowing how many competitors will enter the market nor how quickly the price of the product will decline. As other firms enter the market and the price of a product approaches its marginal cost, the incentive to remain a supplier diminishes.4 At that time, firms make decisions about exiting the market without knowledge of the actions of other firms. Eventually, exit of enough firms supplying a particular product can lead to substantial price increases as the remaining firms operate with little competition, or drug shortages if remaining firms lack the capacity to supply the entire market. These are the drug shortages and price increases observed by Congress. Recently, Hillary Clinton unveiled a policy proposal that would require some pharmaceutical companies to reinvest revenue into research and development. Similarly, Senator Bernie Sanders has proposed several policies to address the pharmaceutical market, including a windfall profits tax and price negotiations directly between the US Department of Health and Human Servicesandmanufacturers.Althoughwell intentioned,these policies do not address the underlying market imperfections, and they risk exacerbating price spikes and shortages by further decreasing incentives for pharmaceutical companies to enter or stay in the generics market.

IP099. Practice Patterns of Fenestrated Aortic Aneurysm Repair: Nationwide Comparison of Z-Fen Adoption at Academic and Community Centers Since Commercial Availability

Objective: Carotid endarterectomy practice patterns, including the use of shunts and cerebral monitoring techniques, are typically surgeon‐dependent and differ greatly on a national level. Prior literature evaluating these techniques is often underpowered for detecting variations in low‐frequency outcomes. The purpose of this study was to evaluate current carotid endarterectomy practice patterns and to allow comparison across surgical approaches using a large national database. Methods: We divided carotid cases entered into the Vascular Quality Initiative database between October 2012 and April 2015 into routine shunting, selective shunting, and never shunting cohorts, excluding endarterectomies performed with concomitant procedures and those with incomplete information on the use of a shunt. The selective group was subdivided into cases with awake, electroencephalography, and stump pressure monitoring. We evaluated differences in practice patterns and compared rates of stroke, death, return to the operating room, reperfusion injury, and re‐exploration after closure across these groups. Multivariate logistic regression models adjusting for risk factors were used to identify predictors of each outcome. Results: Between October 2012 and April 2015, there were a total of 28,457 endarterectomies included in our analysis, of which 14,128 involved routine shunting, 1740 involved never shunting, and 12,489 involved selective shunting. Of the selective cases, 6144 involved electroencephalography monitoring, 2310 involved stump pressure monitoring, and 2052 involved awake monitoring. Unadjusted rates of in‐hospital death and stroke were 0.30% (95% confidence interval [CI], 0.21‐0.39) and 0.78% (95% CI, 0.64‐0.93) for routine shunting and 0.22% (95% CI, 0.14‐0.31) and 0.91% (95% CI, 0.75‐1.08) for selective shunting, respectively. The unadjusted rate of in‐hospital death was lower in the awake monitoring group than in the routine shunting group (0.05% vs 0.30%; P = .037). After adjustment for patient risk factors, the multivariate models showed no difference in rates of any primary outcomes among the groups, although there was a shorter postoperative length of stay for the awake monitoring group compared with the routine shunting group (1.55 days vs 2.00 days, respectively; P < .01). Conclusions: Analysis of the Vascular Quality Initiative registry shows equivalent unadjusted rates of in‐hospital death and stroke across different approaches to shunting and cerebral monitoring with the exception of the awake monitoring group, which has lower unadjusted mortality compared with the routine shunting group. In the risk‐adjusted analysis, however, there are no differences across any of the groups. Given the clinical equivalence of approaches to shunting and cerebral monitoring, further work should evaluate the relative cost of these techniques.

Ruptured Pseudoaneurysm of the Dorsalis Pedis Artery Following Ankle Arthroscopy: A Case Report

BACKGROUND CDC guidelines recommend Neisseria gonorrhoeae, Chlamydia trachomatis, and HIV testing, as well as specific antibiotic regimens in the diagnosis and treatment of pelvic inflammatory disease (PID), although latitude in adhering to these guidelines is common. We hypothesized that adherence to CDC guidelines for antibiotic regimens and laboratory testing, coverage for anaerobic organisms, and the use of diagnostic imaging techniques do not differ significantly between practitioners with emergency medicine (EM) versus obstetrics and gynecology (OB-GYN) training. MATERIALS AND METHODS We conducted a retrospective medical chart review on patients (N = 351) discharged with a diagnosis of PID over a 20-month period at two neighboring emergency care facilities-one with EM-trained providers and the other with OB-GYN-trained providers. RESULTS Adjusted for demographic predictors and chief complaint, there was no significant difference in adherence to N. gonorrhoeae and C. trachomatis antibiotic coverage guidelines between the two facilities (adjusted odds ratio [AOR] 1.34; 95% CI 0.66-2.74), using the OB-GYN facility in the numerator of the AOR. Anaerobic coverage was significantly more common at the OB-GYN facility (AOR 9.11; 95% CI 5.36-15.48). Both sites had very low rates of adherence to CDC laboratory testing guidelines with overall rates of adherence at 4.0% (95% CI 1.9%-5.9%). Utilization of diagnostic tests differed greatly between facilities: ultrasound utilization was 66.7% (95% CI 58.2%-75.2%) at the OB-GYN facility and 39.7% (95% CI 33.4%-45.9%) at the EM facility. CONCLUSIONS The diagnostic pathway for PID and adherence to guidelines differ significantly depending on physician specialty and practice environment, suggesting the need for further standardization, perhaps with cross-disciplinary training.

Engineering Insights for Multiplexed Real-Time Nucleic Acid Sequence-Based Amplification (NASBA): Implications for Design of Point-of-Care Diagnostics

Case:We describe the case of a pseudoaneurysm of the dorsalis pedis artery that developed following a repeat ankle arthroscopy for persistent osseous impingement. The patient underwent attempted fluid aspiration for a presumed effusion, and ultimately experienced rupture of the pseudoaneurysm with substantial blood loss, which required emergency vascular repair. Conclusion:Anterior tibial artery and dorsalis pedis artery pseudoaneurysms are relatively rare, but they are well-documented complications of ankle arthroscopy; however, their clinical importance is poorly understood. To our knowledge, this is the first reported case of a ruptured pseudoaneurysm of the dorsalis pedis artery following ankle surgery, and it highlights the need for timely diagnosis.

Impact of Cerebral Monitoring and Shunting on Outcomes in Carotid Endarterectomy

Context: Over the past decade, a number of endovascular approaches have evolved to treat aortic aneurysms with anatomy that is not amenable to traditional endovascular repair, although the optimal practice and referral patterns remain in question. The Zenith fenestrated (Z-Fen) endograft (Cook Medical) represents the first commercially available fenestrated graft product in the United States. Objective: We aim to quantify practice patterns in Z-Fen use during the first 5 years of commercial availability, and we identify predictors of high and low uptake. Design, Setting, and Patients: This is a retrospective review of complete order records for Z-Fen endografts since June 2012. We performed univariate and multivariate regressions of predictors that surgeons and centers would be in the top and bottom quartiles of annual Z-Fen use. Results: Since June 15, 2012, 744 surgeons have been trained to use Z-Fen, and 4133 cases have been performed at 409 trained centers. The average annual number of cases per trained surgeon was 4.46 [95% confidence interval (CI), 3.58-5.70]; however, many surgeons performed few or no cases following training, and there was a skew toward users with low average annual volumes (25th percentile 1.23, 50th percentile 2.35, 75th percentile 4.93, and 99th percentile 33.29). Predictors of high annual use in the years following training included academic center (aOR 5.87, P = .001) and training within the first 2 years of availability (aOR 46.23, P < .001). Conclusion: While there is literature supporting the safety and efficacy of Z-Fen, adoption has been relatively slow in an era when the vast majority of vascular surgeons have advanced endovascular skills. Given the training and resources required to use fenestrated or branched aortic endovascular devices, referral patterns should be determined and training should be focused on centers with high expected volumes.

VESS03. Evaluating the Efficacy of Selective Shunting and Cerebral Monitoring During Carotid Endarterectomy Using the VQI Database

Objectives: The goal of this study was to compare outcomes of endovascular aneurysm repair (EVAR) with contemporary volume-dependent sac embolization with fibrin glue and coils (Embo-EVAR), vs endovascular aneurysm sealing system (EVAS) with the Nellix device (Endologix Inc, Irvine, Calif) in the prevention of type II endoleaks (ELII) and their complications. Methods: This retrospective study included patients with abdominal aortic aneurysm elected for EVAR and identified as “at risk” for ELII in two vascular centers between 2014 and 2016. The definition “at risk” for ELII was patency of inferior mesenteric artery (IMA) with >3 mm diameter; patency of at least three pairs of lumbar arteries, or two pairs of lumbar arteries plus sacral artery or accessory renal artery or any diameter patent IMA. EVAS was performed according to device instructions for use. Overall, 130 patients underwent endovascular repair (Embo-EVAR, n 1⁄4 75 [57.7%]; EVAS, n 1⁄4 55 [42.3%]). ELII rates during follow-up were compared. Freedom from any reintervention and freedom from ELII-related reintervention were compared using Kaplan-Meier estimates. Results: Patient characteristics and Society for Vascular Surgery comorbidity scores (0.93 6 0.53 vs 0.93 6 0.52; P 1⁄4 1.00) as also mean aneurysm sac diameter (61 6 13 vs 57 6 8 mm; P 1⁄4 .05) and mean sac patent lumen diameter (43 6 10 vs 45 6 9 mm; P 1⁄4 .24) were similar between Embo-EVAR and EVAS. However, Embo-EVAR had a significantly higher number of cases with aneurysm sac patent lumen diameter >60 mm compared to EVAS (8% vs 0%; P 1⁄4 .03). Operative time (151 6 37 vs 115 6 23 minutes; P < .001) and length of hospitalization (4.0 6 4.6 vs 2.9 6 1.8 days; P 1⁄4 .02) were longer in Embo-EVAR compared to EVAS. Freedom from ELII was lower in Embo-EVAR at 3 months (92% vs 100%; P 1⁄4 .04), but was similar between Embo-EVAR and EVAS at 6 (93% vs 98%; P 1⁄4 .40), 12 (90% vs 98%; P 1⁄4 .27), and 24 months (100% vs 100%; P 1⁄4 1.00). At 24 months freedom from any reintervention (Embo-EVAR, 98% vs EVAS; 95%; P 1⁄4 .19) and freedom from ELII-related reintervention were similar (100% for both groups; P 1⁄4 1.00). Within Embo-EVAR, ELII-related reintervention was 0% both for patients with <60 mm and >60 mm sac patent lumen (P 1⁄4 .1). Conclusions: EVAS compared to Embo-EVAR is associated to shorter operative time and length of hospitalization. Although further confirmatory studies are needed, both Embo-EVAR and EVAS seem to be associated to a low rate of ELII and EIIerelated reintervention over the midterm follow-up. Embo-EVAR may be a valid alternative for prevention of EII-complications, also for large aneurysm with a sac patent lumen diameter > 60 mm.