Unclear Benefit Research Articles

Bivalirudin Medication Use Evaluation and Cost Savings Initiative.

Bivalirudin is a parenteral anticoagulant that elicits its effect through inhibition of both free and clot bound-thrombin. Inhibition of thrombin serves as a unique mechanism for anticoagulation when compared to heparin as thrombin serves as the final common pathway for the intrinsic and extrinsic coagulation cascades. Due to unclear benefit over heparin, concerns regarding reversibility, and most importantly cost its use as a parenteral anticoagulant varies by institution. A recent drug expenditure review within our institution noted a significant increase in the contribution bivalirudin had on the overall drug budget. In an effort to establish the rationale for the cost increase, a medication use evaluation was performed. While it was discovered that 625 out of 1364 days of bivalirudin therapy were potentially avoidable, an equally important discovery was the amount of waste that was associated with bivalirudin therapy. Calculating daily requirements for bivalirudin indicated that 60% of patients required less than 100 mg per day. Within this article, we describe a cost-savings initiative to reduce bivalirudin waste and the resulting cost-avoidance following implementation.

Adjuvant gemcitabine-docetaxel chemotherapy for stage I uterine leiomyosarcoma: Trends and survival outcomes.

To assess recent trends of administering adjuvant gemcitabine-docetaxel (GD) chemotherapy for Stage I uterine leiomyosarcoma, and to compare disease-free and overall survival between women who received and did not receive adjuvant GD chemotherapy. All patients diagnosed with Stage I uterine leiomyosarcoma in a California-Colorado population-based health plan inclusive of 2006-2013 were included in a retrospective cohort. Adjuvant GD chemotherapy rates, clinico-pathologic characteristics and survival estimates were assessed. Of 111 women with Stage I uterine leiomyosarcoma, 33 received adjuvant GD (median 4cycles), 77 received no chemotherapy, and 1 patient excluded for non-GD chemotherapy. GD-chemotherapy and no-chemotherapy groups were similar with respect to age, stage (IA/IB), uterine weight, mitotic index, body mass index, and Charlson comorbidity score. Non-Hispanic white women were twice as likely to receive adjuvant chemotherapy as non-white or Hispanic women (37.7 vs. 17.1%, P=0.02). The proportion of women receiving adjuvant GD chemotherapy increased from 6.5% in 2006-2008 to 46.9% in 2009-2013 (P<0.001). There was no significance difference in unadjusted Kaplan-Meyer estimated disease-free (P=0.95) or overall survival (P=0.43) between GD-chemotherapy and no-chemotherapy cohorts. Corresponding adjusted Cox proportional hazard ratios for adjuvant GD chemotherapy compared to no chemotherapy were 1.01 (95% confidence interval [CI] 0.57-1.80, P=0.97) for recurrence and 1.28 (95% CI 0.69-2.36, P-0.48) for mortality. Use of adjuvant GD chemotherapy for Stage I uterine leiomyosarcoma has increased significantly in the last decade, despite unclear benefit. Compared to no chemotherapy, 4-6cycles of adjuvant GD chemotherapy does not appear to alter survival outcomes.

Breast cancer screening in patients with cancers other than breast.

e13095 Background: Screening mammography can detect early breast cancers and reduce subsequent cancer mortality. However, there is a lack of consensus as to what should trigger screening discontinuation. This absence of clear-cut guidelines means that many patients with advanced malignancies continue screening despite unclear benefit. Methods: We performed a retrospective cohort study of female patients diagnosed with a non-breast malignancy to explore the incidence and effects of screening mammography. Female patients, who were diagnosed between 2007 and 2012 with a non-breast malignancy stage II or higher, were cross-referenced with the Vermont mammography screening logs from January 1, 2007 to September 30, 2014. Additional data was collected through chart reviews, in May 2016. Results: Of 1501 women, 398 (26%) who met the above criteria had a screening mammogram within first 5 years of their cancer diagnosis. Of these 398 women, 193 (48.5%) were alive without cancer, 132 (33.2%) had died, and 73 (18.3%) were alive with cancer at the time of chart review. Of those who died, 84 (63.6%) had a stage III or IV cancer. Eighteen (4.5%) had a breast biopsy following a suspicious screening mammogram, resulting in 13 (3.3%) benign diagnoses and 5 (1.3%) breast cancer diagnoses. No patient died of breast cancer. Conclusions: Female patients diagnosed with an advanced non-breast malignancy have a mortality risk that outweighs the known breast cancer mortality benefit from screening mammography. [Table: see text]

Fluoroquinolone prophylaxis for the prevention of central line-associated bloodstream infection in autologous stem cell transplant.

e19508 Background: Patients (Pts) undergoing stem cell transplant (SCT) for the treatment of hematologic malignancy are at increased risk for central line-associated bloodstream infection (CLABSI). Use of prophylactic antibiotics to prevent CLABSI in autologous SCT (autoSCT) is of unclear benefit. We aimed to evaluate the impact of levofloxacin prophylaxis on reducing CLABSI in autoSCT. Methods: Pts undergoing autoSCT at the University of Pennsylvania received levofloxacin prophylaxis during a 6-month intervention period from 1/13/2016 - 7/12/2016. Levofloxacin was administered from autoSCT until day 13, absolute neutrophil count &gt; 500/mm3, or febrile neutropenia. Outcomes were compared to a retrospective cohort who underwent autoSCT, but did not receive routine antibacterial prophylaxis during the previous year (1/13/2015 – 1/12/2016). The primary endpoint was incidence of CLABSI assessed using Cox proportional hazards regression. Results: A total of 243 pts underwent autoSCT, with 69 receiving levofloxacin prophylaxis during the intervention period. Median age was 59 yrs, 74% had multiple myeloma, and 58% received melphalan 200mg/m2. Median duration of neutropenia was 6 days. CLABSI rate was reduced from 18.4% during the baseline period to 7.3% during the intervention period ( P= 0.03). There were no significant differences in characteristics between the baseline and intervention groups except for liver disease (1% versus 5%, P= 0.03). On multivariable analysis, levofloxacin prophylaxis was associated with a significant reduction in CLABSI incidence (HR 0.33; 95% CI 0.12-0.88; P= 0.02), as was underlying multiple myeloma (HR 0.38; 95% CI 0.20-0.74; P= 0.004) and liver disease (HR 4.31; 95% CI 0.99-18.8; P= 0.05). There was also a reduction in neutropenic (NTP) fever (OR 0.21; 95% CI 0.11-0.38; P&lt; 0.001) and a trend toward reduction in ICU transfer for sepsis (OR 0.13; 95% CI 0.01-1.39; P= 0.08) in patients receiving levofloxacin prophylaxis. There were no significant differences in rates of secondary BSIs, C. difficileinfection, or mortality. Conclusions: Levofloxacin prophylaxis was effective in reducing CLABSI and NTP fever in patients undergoing autoSCT.

Abstract 033: Understanding Diagnostic Factors Predicting Negative Coronary Angiography in Patients With Suspected Ischemic Heart Disease: Can We Prevent the Cost of Unnecessary Procedures?

Background: Low risk patients with suspected coronary ischemic syndrome (CIS) undergo hospital procedures despite unclear benefit. False negative evaluations can contribute to unnecessary testing that increases cost. This analysis stratified the likelihood of non-obstructive disease at time of coronary angiography (CA) to determine predictors of a negative study and assessed subsequent costs resulting from negative CA. Methods: 564 coronary angiograms were performed during 2013 at a single institution. Patients with ST-segment elevation myocardial infarction, cardiac arrest, multiple angiograms, or a clear non-CIS indication for CA (i.e. pre valve surgery) were excluded. 171 patients were included for retrospective chart review and categorized by age, race, gender, body mass index, blood pressure, chest pain quality, biomarker elevation, electrocardiographic findings, and clinical features that include hypertension, lipid status, diabetes, chronic kidney disease, psychiatric disease and substance abuse. These data were then analyzed by univariate assessment and logistic regression models for the multivariate predictors of factors associated with negative CA. Cost analysis was performed using a consumer based average cost database and direct hospital laboratory expense data. Results: Of the 171 patients studied, nearly half (47%) did not have obstructive coronary artery disease. The adjusted odds of negative CA were significantly elevated, in order of predictability, with the absence of chest pain (odds ratio (OR) 7.28, p = 0.0004), atypical chest pain (OR 7.13, p &lt; 0.0001), African American race (OR 4.87, p = 0.0033), no diabetes (OR 4.25, p = 0.0026), female gender (OR 3.70, p = 0.0038), normal Troponin-I level (OR 3.16, p = 0.0208), no hyperlipidemia (OR 2.96, p = 0.0107), and low troponin level 0.033 - 0.1 ng/mL (OR 2.96, p = 0.0025). The total cost of negative CA was $749,088, or $9,363 per patient. Total avoidable direct catheterization laboratory expense was $251,000, or $3,137 per patient. Conclusion: In the evaluation of CIS, a large number of patients that undergo CA have no evidence of obstructive disease. Further study of characteristics that predict the absence of obstructive disease would help reduce the frequency and substantial cost of unnecessary invasive procedures.

Estimating the impact of adopting the revised United Kingdom acetaminophen treatment nomogram in the U.S. population

Background: Acetaminophen toxicity is common in clinical practice. In recent years, several European countries have lowered the treatment threshold, which has resulted in increased number of patients being treated at a questionable clinical benefit.Objective: The primary objective of this study is to estimate the cost and associated burden to the United States (U.S.) healthcare system, if such a change were adopted in the U.S.Methods: This study is a retrospective review of all patients age 14 years or older who were admitted to one of eight different hospitals located throughout the U.S. with acetaminophen exposures during a five and a half year span, encompassing from 1 January 2008 to 30 June 2013. Those patients who would be treated with the revised nomogram, but not the current nomogram were included. The cost of such treatment was extrapolated to a national level.Results: 139 subjects were identified who would be treated with the revised nomogram, but not the current nomogram. Extrapolating these numbers nationally, an additional 4507 (95%CI 3641–8751) Americans would be treated annually for acetaminophen toxicity. The cost of lowering the treatment threshold is estimated to be $45 million (95%CI 36,400,000–87,500,000) annually.Conclusions: Adopting the revised treatment threshold in the U.S. would result in a significant cost, yet provide an unclear clinical benefit.

Abstract TP29: Benefit of Intravenous Alteplase Prior to Mechanical Thrombectomy of Large Vessel Occlusion Ischemic Stroke

Purpose: Intravenous alteplase (IV-tPA) in combination with mechanical thrombectomy is the current standard treatment for ischemic stroke due to large vessel occlusion (LVO). IV-tPA has poor revascularization rate in LVO, and the benefit to the patient with LVO is unclear. The purpose of this study was to compare outcomes between patients with LVO who underwent thrombectomy alone and patients who received IV-tPA prior to thrombectomy. Materials and Methods: We searched our institutional database for patients who presented with acute strokes between 1/2008 and 12/2014. We reviewed all clinical data and images of consecutive patients that underwent thrombectomy. Patients with ASPECT score less than 5 were excluded from the analysis. Group 1 received IV-tPA prior to thombectomy. Group 2 underwent thrombectomy alone. Results: In Group 1, 67 patients (32 males) were identified with mean age of 65 years, mean ASPECT score of 7.1, mean initial NIHSS of 16, 58 (87%) with M1 occlusion and 9 (13%) with ICA occlusion. In Group 2, 46 patients (29 males) were identified with mean age of 66, mean ASPECT score of 7.4, mean initial NIHSS of 15, 40 (87%) with M1 occlusion and 6 (13%) with ICA occlusion. There were no significant differences in the baseline characteristics except that more males were represented in the Group 2. TICI 2b or greater revascularization was achieved at similar rates in both groups - 61% and 63% of patients in Group 1 and Group 2, respectively. Stentriever thrombectomy was performed in 43% vs 50% in Group 1 and Group 2, respectively. Mean 3-month follow up modified Rankin scale score was 3.4 in both groups. Conclusions: Our analyses suggest that iv-tPA for LVO does not improve outcomes if the patient ultimately undergoes mechanical thrombectomy. IV-tPA may carry unnecessary cost in these patients with unclear benefit. Also, the majority of the patients in Group 2 presented with “wake-up strokes” or unknown time of onset and longer time to revascularization. Mechanical thrombectomy alone was the major factor in determining outcome regardless of iv-tPA administration.

Treatment of atrial fibrillation with warfarin among older adults with end stage renal disease.

There is increasing evidence questioning the use of warfarin for atrial fibrillation (AF) among older adults with end stage renal disease (ESRD). We assessed the patterns and determinants of warfarin utilization among these patients in the US. We assembled a cohort of older adults (age ≥65) undergoing dialysis with incident AF from July 2007 to November 2011 from the US Renal Data System (USRDS). We used descriptive statistics to characterize warfarin utilization within 30 days of AF discharge, and logistic regression to quantify patient characteristics associated with warfarin initiation. Among 5730 older adults undergoing dialysis with incident AF, 15.5% initiated warfarin. Among 2906 patients with high risk of bleeding, 12.7% initiated warfarin; whereas 14.9% initiated warfarin among 4824 patients with high risk of stroke. After adjustment for patient characteristics, warfarin initiation was lower among patients who were older [odds ratio (OR) = 0.74 per 10-year increase, 95% confidence interval (CI) 0.66-0.83] and those with a history of diabetes (OR = 0.75, 95% CI 0.63-0.90), myocardial infarction (OR = 0.64, 95% CI 0.50-0.80), or bleeding (OR = 0.63, 95% CI 0.50-0.80). There was no association between sex, race, or dialysis modality and warfarin initiation. Among patients who initiated warfarin, 46.8% discontinued warfarin use after a median treatment length of 8.6 months. Despite the unclear benefit and increased bleeding risk of warfarin treatment in patients with ESRD, 1 in 8 older adults undergoing dialysis with incident AF in the US who had high risk of bleeding used warfarin. Changes to warfarin therapy due to discontinuation were common after initiation.

Exploring the Reality of Using Patient Experience Data to Provide Resident Feedback: A Qualitative Study of Attending Physician Perspectives.

Little is known about the attitudes of faculty and residents toward the use of patient experience data as a tool for providing resident feedback. The purpose of this study was to explore the attitudes of teaching faculty surrounding patient experience data and how those attitudes may influence the feedback given to trainees. From July 2013 to August 2013, we conducted in-depth, face-to-face, semistructured interviews with 9 attending physicians who precept residents in internal medicine at 2 continuity clinics (75% of eligible attendings). Interviews were coded using conventional content analysis. Content analysis identified six potential barriers in using patient experience survey data to provide feedback to residents: 1) perceived inability of residents to learn or to incorporate feedback, 2) punitive nature of feedback, 3) lack of training in the delivery of actionable feedback, 4) lack of timeliness in the delivery of feedback, 5) unclear benefit of patient experience survey data as a tool for providing resident feedback, and 6) lack of individualized feedback. Programs may want to conduct an internal review on how patient experience data is incorporated into the resident feedback process and how, if at all, their faculty are trained to provide such feedback.

Axillary evaluation and lymphedema in women with ductal carcinoma in situ.

Axillary evaluation in women with ductal carcinoma in situ (DCIS) is increasing; however, this may introduce additional morbidity with unclear benefit. Our objective was to examine the morbidity and mortality associated with axillary evaluation in DCIS. We conducted a retrospective cohort study of 10,504 women aged 65-90 years with DCIS who underwent breast conserving surgery between 2002 and 2012 using SEER-Medicare database. Patients were categorized by receipt of axillary evaluation with either sentinel lymph node biopsy (SLNB) or axillary node dissection (ALND). We determined the incidence of lymphedema treatment as defined by diagnostic and procedural codes, as well as 10-year breast cancer-specific and all-cause mortality. 18.3% of those treated with BCS and 69.4% of those treated with mastectomy had an axillary evaluation. One year after treatment, 8.2% of women who had an axillary evaluation developed lymphedema, compared to 5.9% of those who did not. In a multivariable Cox proportional hazard model, the incidence of lymphedema was higher among those who underwent axillary evaluation (HR 1.22, 95% CI 1.04-1.45). Overall 10-year breast cancer-specific survival was similar between both groups (HR 0.83, 95% CI 0.40-1.74). Only 44 (0.40%) women died of breast cancer; receipt of axillary evaluation did not alter overall survival. Axillary evaluation is commonly performed in women with DCIS, especially those undergoing mastectomy. However, women who receive an axillary evaluation have higher rates of lymphedema, without breast cancer-specific or overall survival benefit. Efforts should be made to determine the population of women with DCIS who benefit from this procedure.

A multi-dimensional metric for facilitating sustainable food choices in campus cafeterias

Demand-side initiatives to alter food choices have been repeatedly identified as important tools in reducing the environmental and resource use impacts of our global food systems, and effective strategies to identify and motivate key dietary changes are needed. The environmental and resource use impacts of the most common meals served in the undergraduate residence cafeterias at McGill University in Montreal are evaluated and presented, to inform sustainable food choices in an easy to use manner. The life-cycle land and water use, and greenhouse gas emissions for the 19 most-used ingredients are calculated and compared for different iterations of two typical meals using these ingredients, accounting for multiple origins, methods of production of ingredients, and meal types. These three metrics are kept distinct to better communicate trade-offs and inform decision-making. Overall, meals containing beef and cheese have 2–12 times higher associated water, land use and greenhouse gas emissions impacts than meals with other protein sources and drive impacts more than provenance or production methods assessed. The impacts of eggs and chicken are comparable to or lower than those of many plant-based ingredients. This suggests that the adoption of a lacto-vegetarian diet has an unclear environmental benefit; eating chicken instead of cheese would be more beneficial in some cases. For some ingredients, impacts vary greatly depending on their provenance, independent of transport. There are also substantial trade-offs between the metrics for greenhouse vegetables, but these trade-offs are minimized in milder climates. Given this high context dependence, greater transparency is needed in supply chains at the consumer level, to improve the reliability of food sustainability metrics.

A revisit of the devastating outcome of leptomeningeal disease.

e13504 Background: Leptomeningeal metastasis (LM) represents a devastating complication of malignancies by forming tumor deposits on the leptomeninges at about 5% to 8% of cancer patients (Pts). Standard therapies include radiotherapy (RT) to focal involved areas, systemic and/or intrathecal (IT) chemotherapies which have been recommended for palliation but with unclear benefit toward survival. This study is to review the pattern of the clinical practice and outcomes on Pts with LM who have received care at Henry Ford Hospital between 2004 and 2014 Methods: A retrospective study targeted all Pts of LM (icd-9 code 198.4) between 01/01/2004 and 01/01/2014. Pts with primary brain, orbital and spinal lesions as well as Pts with cord compressions were excluded from this study. LM Pts were included based on MRI images, cerebral spinal fluid (CSF) cytology and/or dural biopsy. Data from onset of primary tumor, therapeutic interventions, methods of LM diagnosis, duration (days) from initial cancer onset to LM diagnosis, then from LM diagnosis to death were collected and analyzed as shown Results: 328 Pts with LM (icd-9: 198.4) were identified, but 58 Pts fulfilled inclusions. Of 58 Pts, 22 (38%) had breast cancer (38%), 12 (21%) NSCLC. LM was diagnosed in 34 Pts (59%) based on MRI findings, 4 (6%) by CSF cytology and 19 (33%) by both. Majority (37 Pts, 64%) received therapy after LM diagnosis: 16 (27%) received IT chemotherapy, 15 (26%) received RT while 6 (10%) received both. Twenty-one of LM Pts (36%) received no treatment under various circumstances. Of 58 Pts, the median time from cancer onset to LM diagnosis was 686 days while median overall survival (OS) was 1038 days, and median OS from LM to death was 95 days. Survival difference was observed for Pts (37, 64%) received LM-directed treatment as 113 days but only 61 days for those received no therapies Conclusions: LM is a prognostic complication in malignancies. It poses a grave challenge due to limited therapeutics that only carry modest survival benefit. Data from these 58 Pts shown a benchmarks of survival from LM diagnosis was 4 months with treatment, and 2 months without. These are consistent with published data over last decades without improvement. Therefore, more clinical researches in LM diagnosis and therapies are needed

Acute Fibrinous and Organizing Pneumonia Associated With Allogenic Hematopoietic Stem Cell Transplant Successfully Treated With Corticosteroids: A Two-Patient Case Series.

Acute fibrinous and organizing pneumonia (AFOP) is an extremely rare, relatively new, and distinct histological pattern of acute lung injury characterized predominately by the presence of intra-alveolar fibrin and associated organizing pneumonia. AFOP may be idiopathic or associated with a wide spectrum of clinical conditions. It has a variable clinical presentation from mild respiratory symptoms to that similar to the acute respiratory distress syndrome. Currently there is no consensus on treatment, and corticosteroids previously were of unclear benefit. To date, there are less than 40 cases of AFOP reported in the literature and only one has been linked to hematopoietic stem cell transplantation. Here we report the first case series of 2 patients who developed AFOP following allogenic stem cell transplant that were successfully treated with high-dose corticosteroids.

Surgical Treatment of Gastro-Esophageal Reflux Disease: A Review of Concepts Misguiding the Indications for Surgery

Context: Clinical therapies and surgical interventions are the acceptable treatments for gastro-esophageal reflux disease (GERD). Referrals for surgery are yet limited, because of disadvantages associated to surgical treatment, including: (a) high rate of mortality; (b) high risk of side eects, especially dysphagia; (c) need for acid-reducing medications after surgery; (d) need for revision surgery; (e) unclear benefit of surgery on the risk of cancer; and (f) dierences in the outcomes between a community setting and a tertiary care center. In contrast, surgeons report excellent outcomes after anti-reflux operation. Evidence Acquisition: A thorough search in literature was performed with predefined keywords to identify relevant articles pub- lished from 1975 to January 2015, in order to analyze the complications from the aspect of current surgeon's perspective. Results: Our review showed that: (a) the mortality rate of the surgical procedure is negligible and PPI therapy is also accompanied with mortality; (b) there is a 5% chance of severe dysphagia after anti-reflux operation; (c) postsurgical use of PPI is not an indication of surgical failure, but often represents misuse of the medication; (d) there is a 5% chance of re-operation after surgery, often because of severe dysphagia; (e) reduction in the risk of adenocarcinoma is probable but still controversial; and (f) good results can be achieved in a community setting. Conclusions: A significant number of patients would benefit from surgical therapy to treat their GERD symptoms, but some incor- rect beliefs still misguide the indications for the surgical procedure.

Health Economic Impact and Prospective Clinical Utility of Oncotype DX® Genomic Prostate Score.

Prostate cancer (CaP) will be diagnosed in approximately 181,000 American men in 2016. Despite the high number of deaths from CaP in the United States, the disease has a protracted natural history and many men diagnosed with CaP will not die of the disease regardless of treatment. Unfortunately, identification of men with truly indolent/ nonaggressive CaP is challenging; limitations of conventional diagnostic modalities diminish the ability of physicians to accurately stage every case of CaP based on biopsy results alone. The resulting uncertainty in prognosis may prompt men with low-risk CaP to proceed to morbid and expensive treatments for an unclear survival benefit. Incorporation of the Genomic Prostate Score (GPS) as part of the decision algorithm for patients with National Comprehensive Cancer Network very low-risk and low-risk cancer led to a substantial increase in uptake of active surveillance and substantial cost savings. GPS provides physicians and patients with an additional tool in assessing personalized risk and helps guide individual decision making.

Computer-Navigated Total Knee Arthroplasty Utilization.

Computer-navigated total knee arthroplasty (CN-TKA) has been used to improve component alignment, though the evidence is currently mixed on whether there are clinically significant differences in long-term outcomes. Given the established increased costs and operative time, we hypothesized that the utilization rate of CN-TKA would be decreasing relative to standard TKA in the Medicare population given the current health care economic environment. We queried 1,914,514 primary TKAs performed in the entire Medicare database from 2005 to 2012. Current Procedural Terminology (CPT) and International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes were used to identify and separate CN-TKAs. Utilization of TKA was compared by year, gender, and region. Average change in cases per year and compound annual growth rate (CAGR) were used to evaluate trends in utilization of the procedure. We identified 30,773 CN-TKAs performed over this time period. There was an increase in utilization of CN-TKA per year from 984 to 5,352 (average = 572/year, R (2) = 0.85, CAGR = 23.58%) from 2005 to 2012. In contrast, there was a slight decrease in overall TKA utilization from 264,345 to 230,654 (average = 4297/year, R (2) = 0.74, CAGR = - 1.69%). When comparing proportion of CN-TKA to all TKAs, there was an increase from 0.37 to 2.32% (average 0.26%/year, R (2) = 0.88, CAGR = 25.70%). CN-TKA growth in males and females was comparable at 24.42 and 23.11%, respectively. The South region had the highest growth rate at 28.76%, whereas the Midwest had the lowest growth rate at 15.51%. The Midwest was the only region that peaked (2008) with a slow decline in utilization until 2012. Despite increased costs with unclear clinical benefit, CN-TKA is increasing in utilization among Medicare patients. Reasons could include patient preference, advertising, proper of coding the procedure, and increased publicly available information about arthroplasty options.

The Value of Serum CA125 in the Diagnosis of Borderline Tumors of the Ovary: A Subanalysis of the Prospective Multicenter ROBOT Study.

The value of the serum tumor marker CA125 in borderline tumors of the ovary (BOTs) is not well defined, with unclear benefit in both diagnosis and follow-up. The aim of the present project was to identify the predictive value of CA125 for stage and relapse. CA125 data were extracted from the ROBOT multicenter study of patients with BOT treated between 1998 and 2008 in 24 German centers. While patients' data were retrieved retrospectively from hospital records and clinical tumor registries, follow-up and independent central pathology review were performed prospectively. We identified 127 patients from the ROBOT database fulfilling the eligibility criterion of available CA125 at initial diagnosis. Eighty-three (65.3%) patients had increased CA125 levels (>35 U/L). Of the patients, 85.0% presented with serous and 13.4% with mucinous BOT histology, whereas 29.9% had stage I disease. Fifteen (11.8%) patients experienced a relapse. Multivariate analysis identified raised CA125, young age, and serous histology as independent predictors of peritoneal implants of any type at initial presentation. Raised CA125 at initial diagnosis was, however, not an independent predictor of future relapse. Elevated CA125 seems to be associated with the presence of peritoneal implants of any type at initial diagnosis of serous BOT, but failed to have any independent predictive value on future relapse. Prospective multicenter studies are warranted to evaluate CA125 measurements in the follow-up management of BOT.

The Effect of Right Ventricular Apical and Nonapical Pacing on the Short- and Long-Term Changes in Left Ventricular Ejection Fraction: A Systematic Review and Meta-Analysis of Randomized-Controlled Trials.

The right ventricular apex (RVA) is the traditional lead site for chronic pacing but in some patients may cause impaired left ventricular (LV) systolic function over time. Comparisons with right ventricular nonapical (RVNA) pacing sites have generated inconsistent results and recent meta-analyses have demonstrated unclear benefit due to heterogeneity across studies. A systematic search for randomized controlled trials that compared LV ejection fraction (LVEF) outcomes between RVNA and RVA pacing was performed up to October 2014. Twenty-four studies (n = 1,628 patients) met the inclusion criteria. To avoid between study heterogeneity two homogenous groups were created; group 1 where studies reported a difference (in favor of RVNA pacing) and group 2 where studies reported no difference between pacing sites. For group 1, weighted mean difference between RVNA and RVA pacing in terms of LVEF at follow-up was 5.40% (95% confidence interval [CI]: 3.94-6.87), related in part to group one's RVA arm demonstrating a significant reduction (mean loss -3.31%; 95% CI: -6.19 to -0.43) in LVEF between study baseline and end of follow-up. Neither of these finding were seen in group 2. Weighted regression modeling demonstrated that inclusion of poor baseline LVEF (<40%) in combination with greater than 12 months follow-up was three times more common in group 1 compared to group 2 (weighted relative risk 2.82; 95% CI: 1.03-7.72; P = 0.043). In patients requiring chronic right ventricular pacing where there is inclusion of impaired baseline LVEF (<40%), RVA pacing is associated with deterioration in LV function relative to RVNA pacing.

Shifting From Volume to Value: Opportunities and Challenges for the Field of Orthopaedic Surgery.

Shifting From Volume to Value: Opportunities and Challenges for the Field of Orthopaedic Surgery.

Androgens/Female Clinical/Female Basic Science.

Editorial Comment: Testosterone therapy for late-onset hypogonadism is a controversial practice. What is not controversial is the need for appropriate patient selection and careful monitoring for treatment emergency adverse events in those patients who do choose to initiate testosterone therapy. While individual practitioners may vary in the details of their follow-up protocols, all experts agree that patients should be followed. This follow-up must include physical examination and routine laboratory testing. This insurance claims database makes clear a distressing reality; there exist a substantial number of U.S. men being treated with testosterone without proper testing before initiation of therapy and/or absence of follow-up serum after therapy has been initiated. As would be expected, clinicians with particular expertise in hypogonadism were more likely to adhere to established guidelines. The issue of PSA screening is itself controversial, and hence, some providers may opt to defer this testing altogether. While deferral of PSA testing may be appropriate in properly counseled patients, it is counter-intuitive, and perhaps medico-legally risky, to avoid PSA testing in a patient receiving a therapy that has been associated with PSA changes and prostate cancer. Setting aside the issue of PSA, it is clearly inappropriate not to test serum testosterone level before starting treatment and/or after therapy has been initiated. While there is controversy about appropriate cutoff levels for “low testosterone,” very few studies support any benefit from supplementation in men with total serum testosterone levels greater than 400 ng/dL; indeed, most studies recommend a much lower cut point around 300 ng/dL. Supplementing men who may have serum levels greater than these cutoffs is potentially risky and of unclear clinical benefit. Unfortunately, providers who are not knowledgeable about established cut-offs are likely less prone to read literature such as this paper. It behooves medical practices and regulatory agencies to ensure that their practitioners adhere to the best available evidence-based guidelines; at a minimum, this should mean pretreatment assessment of serum testosterone levels and follow-up to ensure appropriate supplementation is achieved.