Practice-level variation in statin use and low-density lipoprotein cholesterol control in the United States: Results from the Patient and Provider Assessment of Lipid Management (PALM) registry.

BACKGROUND: Adherence to guideline-recommended statin recommendations in the United States is suboptimal. Patients' likelihood to be treated according to guidelines may vary by the practice in which they are treated. METHODS: Variation in the use of statin therapy in 5445 patients, with known or at high risk for atherosclerotic cardiovascular disease (ASCVD) and meeting a statin treatment indication, was examined across 74 US Patient and Provider Assessment of Lipid Management (PALM) Registry clinics. Multivariable generalized linear mixed modeling was used to determine the median odds ratio (MOR) for statin use and 2013 American College of Cardiology/American Heart Association guideline-recommended statin intensity by practice. MOR quantifies between-practice variation by comparing the odds of receiving guideline-recommended statin treatment in a patient from a randomly selected practice with a similar patient from another random practice. Risk-adjusted low-density lipoprotein cholesterol (LDL-C) control (<100 and <70 mg/dL) was compared among practice tertiles based on percentage of eligible patients receiving recommended statin intensity. RESULTS: Among 74 practices (43.2% cardiology) comprised of 300 healthcare providers enrolling 5445 patients (56.2% with ASCVD), statin use at the guideline-recommended intensity at practices varied widely (12.7-71.4%; adjusted MOR 1.45, 95% confidence interval [CI] 1.35-1.64). Results were consistent when evaluated for any statin use overall (adjusted MOR 1.75, 95% CI 1.48-1.99) and when stratified by primary versus secondary prevention patients. Relative to practices with lowest or mid-tertile statin use of statins, highest tertile clinics were more frequently cardiology practices (68.0% vs 48.0% vs 12.5%, P < .001). Compared with lowest tertile clinics, patients at highest tertile clinics were more likely to achieve LDL-C <70 mg/dL (adjusted odds ratio [OR] 1.49, 95% CI 1.08-2.04) and <100 mg/dL (adjusted OR 1.78, 95% CI 1.41-2.25). CONCLUSIONS: US clinics varied widely in their adherence to guideline recommendations for statin therapy, which contributed to significant differences in LDL-C levels.

Does clinician-reported lipid guideline adoption translate to guideline-adherent care? An evaluation of the Patient and Provider Assessment of Lipid Management (PALM) registry.

BACKGROUND: The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol guideline recommends statin treatment based on patients' predicted atherosclerotic cardiovascular disease (ASCVD) risk. Whether clinician-reported guideline adoption translates to implementation into practice is unknown. OBJECTIVES: We aimed to compare clinician lipid management in hypothetical scenarios versus observed practice. METHODS: The PALM Registry asked 774 clinicians how they would treat 4 hypothetical scenarios of primary prevention patients with: (1) diabetes; (2) high 10-year ASCVD risk (≥7.5%) with high low-density lipoprotein cholesterol (LDL-C; ≥130 mg/dL); (3) low 10-year ASCVD risk (<7.5%) with high LDL-C (130-189 mg/dL); or (4) primary and secondary prevention patients with persistently elevated LDL-C (≥130 mg/dL) despite high-intensity statin use. We assessed agreement between clinician survey responses and observed practice. RESULTS: In primary prevention scenarios, 85% of clinicians reported they would prescribe a statin to a diabetic patient and 93% to a high-risk/high LDL-C patient (both indicated by guidelines), while 40% would prescribe statins to a low-risk/high LDL-C patient. In clinical practice, statin prescription rates were 68% for diabetic patients, 40% for high-risk/high LDL-C patients, and 50% for low-risk/high LDL-C patients. Agreement between hypothetical and observed practice was 64%, 39%, and 52% for patients with diabetes, high-risk/high LDL-C, and low-risk/high LDL-C, respectively. Among patients with persistently high LDL-C despite high-intensity statin treatment, 55% of providers reported they would add a non-statin lipid-lowering medication, while only 22% of patients were so treated. CONCLUSIONS: While the majority of clinicians report adoption of the 2013 ACC/AHA guideline recommendations, observed lipid management decisions in practice are frequently discordant.

Statin Use and Adverse Effects Among Adults >75 Years of Age: Insights From the Patient and Provider Assessment of Lipid Management (PALM) Registry.

BACKGROUND: Current statin use and symptoms among older adults in routine community practice have not been well characterized since the release of the 2013 American College of Cardiology/American Heart Association guideline. METHODS AND RESULTS: We compared statin use and dosing between adults >75 and ≤75 years old who were eligible for primary or secondary prevention statin use without considering guideline-recommended age criteria. The patients were treated at 138 US practices in the Patient and Provider Assessment of Lipid Management (PALM) registry in 2015. Patient surveys also evaluated reported symptoms while taking statins. Multivariable logistic regression models examined the association between older age and statin use and dosing. Among 6717 people enrolled, 1704 (25%) were >75 years old. For primary prevention, use of any statin or high-dose statin did not vary by age group: any statin, 62.6% in those >75 years old versus 63.1% in those ≤75 years old (P=0.83); high-dose statin, 10.2% versus 12.3% in the same groups (P=0.14). For secondary prevention, older patients were slightly less likely to receive any statin (80.1% versus 84.2% [P=0.003]; adjusted odds ratio, 0.81; 95% confidence interval, 0.66-1.01 [P=0.06]), but were much less likely to receive a high-intensity statin (23.5% versus 36.2% [P<0.0001]; adjusted odds ratio, 0.54; 95% confidence interval, 0.45-0.65 [P=0.0001]). Among current statin users, older patients were slightly less likely to report any symptoms (41.3% versus 46.6%; P=0.003) or myalgias (27.3% versus 33.3%; P<0.001). CONCLUSIONS: Overall use of statins was similar for primary prevention in those aged >75 years versus younger patients, yet older patients were less likely to receive high-intensity statins for secondary prevention. Statins appear to be similarly tolerated in older and younger adults.

Correction to: Assessment of the 1% of Patients with Consistent < 15% Reduction in Low-Density Lipoprotein Cholesterol: Pooled Analysis of 10 Phase 3 ODYSSEY Alirocumab Trials.

The original version of this article unfortunately contained a mistake in the Discussion section.

Assessment of the 1% of Patients with Consistent < 15% Reduction in Low-Density Lipoprotein Cholesterol: Pooled Analysis of 10 Phase 3 ODYSSEY Alirocumab Trials.

PURPOSE: Clinical trials of statins and other lipid-lowering therapies (LLTs) often report large inter-individual variations in their effects on low-density lipoprotein cholesterol (LDL-C). We evaluated apparent hyporesponsiveness to the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab (defined as < 15% LDL-C reduction from baseline at all timepoints) using data from 10 Phase 3 trials (3120 hypercholesterolemic patients). METHODS: This report assessed the LDL-C percent reduction from baseline at weeks 4-104 (depending on study), and alirocumab serum levels and antidrug antibodies, in patients with apparent hyporesponsiveness. RESULTS: Among the 3120 patients evaluated, 98.9% responded to alirocumab, and 33 (1.1%) had < 15% LDL C reduction at all measured timepoints. Pharmacokinetics data indicated that 13/33 apparent hyporesponders had not received alirocumab; no pharmacokinetics data were available for 14/33, and 6/33 had detectable alirocumab. For the six patients with confirmed alirocumab receipt, the degree of adherence to pre-study concurrent LLTs could not be determined after study start; one of these patients had persistent antidrug antibodies. CONCLUSIONS: Apparent hyporesponsiveness to alirocumab appeared to be due to lack of receipt of alirocumab determined by serum alirocumab levels, possible lack of adherence to concurrent LLTs, a theoretical and rare possibility of biological non-responsiveness due to persistent antidrug antibodies, or other causes, as yet unidentified.

The Relative Burden of Menopausal and Postmenopausal Symptoms versus Other Major Conditions: A Retrospective Analysis of the Medical Expenditure Panel Survey Data.

BACKGROUND: The direct costs associated with menopausal and postmenopausal symptoms (hereafter "menopausal symptoms") may include the costs of physician and emergency department visits, medications, laboratory testing, and the management of side effects. However, much remains unknown about the costs related to menopausal symptoms, including how they compare with the costs of other diseases that are common among menopausal women. OBJECTIVE: To compare the economic burden of menopausal symptoms with other select prevalent chronic conditions among a nationally representative sample of US menopausal women aged 45 to 65 years. METHODS: Women aged 45 to 65 years who have not had a hysterectomy and who participated in the 2010-2012 Medical Expenditure Panel Survey Household Component were included in the analysis. We estimated the direct costs of care associated with the management of menopausal symptoms and compared them with the direct costs of care for other indications, including osteoporosis, influenza, disorders of lipid metabolism, essential hypertension, mood disorders, esophageal disorders, headache, osteoarthritis, urinary tract infections, asthma, glaucoma, anxiety disorder, diabetes, chronic obstructive pulmonary disease/bronchiectasis, and cataract. Regression analyses were used to estimate the differences in direct costs, which included total expenditures and charges for inpatient, outpatient, and emergency department visits. RESULTS: The annual per-patient direct cost of menopausal symptoms was $248 in 2010-2012 dollars. Based on the modeled costs, menopausal symptoms were associated with significantly higher annual costs than osteoporosis, disorders of lipid metabolism, and esophageal disorders; and these annual costs were comparable to those of influenza, asthma, anxiety disorder, essential hypertension, and headache. The direct costs associated with the management of menopausal symptoms were significantly lower than the direct costs associated with osteoarthritis, mood disorders, chronic obstructive pulmonary disease/bronchiectasis, urinary tract infections, diabetes, glaucoma, and cataract. CONCLUSION: The direct costs of care for menopausal symptoms are substantial and are similar to or greater than the direct healthcare costs associated with a number of medical conditions often requiring medical attention in menopausal women.

Impact of a laparoscopic renal surgery mini-fellowship program on postgraduate urologist practice patterns at 3-year followup.

PURPOSE: To assist practicing urologists incorporate laparoscopic renal surgery into their practice we established a 5-day mini-fellowship program with a mentor, preceptor and a potential proctor at our institution. We report the impact of our mini-fellowship program at 3-year followup. MATERIALS AND METHODS: A total of 106 urologists underwent laparoscopic ablative (44) or laparoscopic reconstructive (62) renal surgery training. The 1:2 teacher-to-attendee experience included tutorial sessions, hands-on inanimate and animate skills training, and clinical case observations. Participants were asked to complete a detailed questionnaire on laparoscopic practice patterns 1, 2 and 3 years after the mini-fellowship. RESULTS: The questionnaire response rate at 1 to 3 years was 77%, 65% and 68%, respectively. Of responders 72%, 71% and 71% performed laparoscopic renal surgery at 1 to 3 years, respectively. Of the 106 participants 32 (39%) had previous laparoscopic experience, including 78% who responded to the questionnaire at 3 years. Of those surgeons there was an increase in the practice of laparoscopic radical nephrectomy (88% vs 72%), nephroureterectomy (56% vs 13%), pyeloplasty (40% vs 6%) and partial nephrectomy (32% vs 6%) at 3 years. Of the 106 participants 74 (70%) were laparoscopy naïve, including 48 (65%) who responded to the questionnaire at 3 years. The take rate in this group was 76%, 52%, 34% and 23% for laparoscopic radical nephrectomy, nephroureterectomy, pyeloplasty and partial nephrectomy, respectively. Of the participants 90% indicated that they would recommend this training to a colleague. CONCLUSIONS: An intensive 5-day laparoscopic ablative and reconstructive renal surgery course enabled postgraduate urologists to effectively introduce and expand the volume and breadth of their laparoscopic renal surgery practice.

A microsimulation of the cost-effectiveness of maraviroc for antiretroviral treatment-experienced HIV-infected individuals.

PURPOSE: Maraviroc (MVC) is the first approved CCR5 antagonist. The aim of this study was to explore the cost-effectiveness of MVC in treatment-experienced or treatment-resistant HIV-infected adults. METHODS: The validated HIV microsimulation model ARAMIS was used to predict clinical and economic outcomes of treating patients with optimized background therapy (OBT) alone, as compared to a strategy of testing for the patient's viral tropism and treating with OBT with or without (+/-) MVC in a cohort corresponding to the MOTIVATE screening cohort. RESULTS: Compared to treatment with OBT alone, a treatment strategy of OBT +/- MVC (twice daily) according to tropism test result was predicted to increase CD4+ cell count after 5 years (from mean 249 to 360 cells/microL), undiscounted life expectancy (7.6 to 8.9 years), and quality-adjusted life years (QALYs; from 4.99 to 5.71) for an additional $40,500, giving an incremental cost-effectiveness ratio of $56,400 per QALY gained. The result was relatively insensitive to alternative clinical and cost assumptions within reasonable ranges, but for individuals with HIV susceptible to only two or fewer components of OBT, the ICER decreased to $52,000 per QALY gained. CONCLUSION: MVC is cost-effective, especially among individuals with few remaining options for active antiretroviral therapy.

Long-term impact of a robot assisted laparoscopic prostatectomy mini fellowship training program on postgraduate urological practice patterns.

PURPOSE: Robot assisted laparoscopic prostatectomy has stimulated a great deal of interest among urologists. We evaluated whether a mini fellowship for robot assisted laparoscopic prostatectomy would enable postgraduate urologists to incorporate this new procedure into clinical practice. MATERIALS AND METHODS: From July 2003 to July 2006, 47 urologists participated in the robot assisted laparoscopic prostatectomy mini fellowship program. The 5-day course had a 1:2 faculty-to-attendee ratio. The curriculum included lectures, tutorials, surgical case observation, and inanimate, animate and cadaveric robotic skill training. Questionnaires assessing practice patterns 1, 2 and 3 years after the mini fellowship program were analyzed. RESULTS: One, 2 and 3 years after the program the response rate to the questionnaires was 89% (42 of 47 participants), 91% (32 of 35) and 88% (21 of 24), respectively. The percent of participants performing robot assisted laparoscopic prostatectomy in years 1 to 3 after the mini fellowship was 78% (33 of 42), 78% (25 of 32) and 86% (18 of 21), respectively. Among the surgeons performing the procedure there was a progressive increase in the number of cases each year with increasing time since the mini fellowship training. In the 3 attendees not performing the procedure 3 years after the mini fellowship training the reasons were lack of a robot, other partners performing it and a feeling of insufficient training to incorporate the procedure into clinical practice in 1 each. One, 2 and 3 years following the mini fellowship training program 83%, 84% and 90% of partnered attendees were performing robot assisted laparoscopic prostatectomy, while only 67%, 56% and 78% of solo attendees, respectively, were performing it at the same followup years. CONCLUSIONS: An intensive, dedicated 5-day educational course focused on learning robot assisted laparoscopic prostatectomy enabled most participants to successfully incorporate and maintain this procedure in clinical practice in the short term and long term.

Robot assisted laparoscopic pyeloplasty: a review of the current status.

BACKGROUND: Over the last decade minimally invasive endourologic and laparoscopic techniques have become the first line therapies for primary UPJ obstruction. Robotic assisted laparoscopic pyeloplasty for the correction of ureteropelvic junction has achieved outcomes comparable to those of open and laparoscopic techniques. We present a comprehensive review of the current literature of robotic assisted pyeloplasty. METHODS: We performed a systemic review of all the current literature examining demographic data, intra operative parameters and post-operative outcomes. RESULTS: In most published series in the literature, the operative time ranges from 122 to 300 minutes and the operative time ranges from 27 to 77 ml. Most series considers subjective improvement in the symptoms and improved drainage on post-operative diuretic renal scan as the measures of success. The reported success rates vary from 89 to 100%. CONCLUSION: Robotic pyeloplasty is a feasible alternative to laparoscopic pyeloplasty. Short-term results indicate equivalent outcomes with the laparoscopic procedure. Long-term studies are still needed to compare robotic and open pyeloplasty outcomes, and to define the role of robotic pyeloplasty in a cost prohibitive health care system.

A novel antiviral intervention results in more accurate assessment of human immunodeficiency virus type 1 replication dynamics and T-cell decay in vivo.

Mathematical models provide an understanding of in vivo replication kinetics of human immunodeficiency virus type 1 (HIV-1). With a novel intervention designed for increased potency, we have more accurately deduced the half-lives of virus-producing CD4(+) T cells, 0.7 day, and the generation time of HIV-1 in vivo, approximately 2 days, confirming the dynamic nature of HIV-1 replication.