Pharmacy Benefit Managers in the Eye of the Storm: Growing Multipartite Scrutiny.

The high cost of prescription drugs in the U.S. remains an ongoing national challenge. A recurring focal point in discussions over this distressing steady state is the role(s) played by Pharmacy Benefit Managers (PBMs) who negotiate drug prices with pharmaceutical manufacturers, conduct drug utilization reviews, engage in disease management, and see to formulary creation. At their inception, the multiple newly established PBMs were arguably intent on constraining the rise of prescription drug prices. At the time of this writing, however, the lion share of a far less competitive PBM market is controlled by CVS Caremark, Express Scripts, and OptumRx. It is this evolving reality which could be interpreted to mean that the PBMs may have become part of the problem, rather than part of the solution. Expanded scrutiny of the PBMs by Federal and State authorities as well as by Professional Medical Associations must not be delayed with an eye toward affording the public with relief from the high cost of prescription drugs.

Factors affecting live birth rates in donor oocytes from commercial egg banks vs. program egg donors: an analysis of 40,485 cycles from the Society for Assisted Reproductive Technology registry in 2016-2018.

OBJECTIVE: To examine the differences in live birth rates (LBRs), with single embryo transfer (SET), using oocytes from program generated egg donors vs. commercial egg bank donors and other factors affecting LBRs using donor oocytes. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 40,485 in vitro fertilization cycles using donor oocytes reported to the Society for Assisted Reproductive Technology registry in 2016-2018. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth rate and cumulative LBR for SET using donor oocytes. RESULT(S): Multivariate results from the first SET from 19,128 cycles, including 15,429 from program generated egg donors and 3,699 from commercial egg banks, showed, when controlling for all other variables, the following: the LBR in the first SET cycle using commercial egg banks was 53.3% compared with 55.4% using program recruited egg donors (odds ratio [OR], 0.92); a reduction in the LBR with increasing recipient age, ages 40-44 years (OR, 0.80), 45-49 years (OR, 0.77), and >49 years (OR, 0.65); a steady decline in the LBR with increases in recipient body mass index above normal; and a steady increase in the LBR in association with >16 oocytes retrieved. Double embryo transfer increased the LBR (SET, 52%, vs. double embryo transfer, 58%) but also significantly increased the multiple pregnancy LBR, with 43% twins and 0.9% triplets. Blastocyst transfer had a higher LBR than cleavage stage embryos (52.5% vs. 39.5%). Intracytoplasmic sperm injection vs. conventional insemination when using fresh oocytes from program donors had similar LBRs. CONCLUSION(S): When performing in vitro fertilization using donor oocytes with SET, the LBR is affected by oocyte source, recipient age, recipient body mass index, stage of embryo at transfer, and number of oocytes retrieved.

Governance of Academic Health Centers and Systems: A Conceptual Framework for Analysis.

Health care has evolved from a cottage industry to a very complex one constituting nearly one-fifth of the U.S. economy. Large aggregated health care systems have evolved primarily for the purpose of optimizing financial performance by capturing greater market share and taking advantage of economies of scale in care delivery. With the noble intent of providing a broader base of support for the academic mission, academic health centers (AHCs) have followed suit by partnering with community hospitals and organizations with variable prior experience in the education and research arenas. Such a strategy makes good business sense, but it creates challenges for the academic mission. Singular emphasis on physicians' clinical productivity enhances financial margin but often reduces faculty time and effort dedicated to the academic mission. While individual AHC governance is varied, the leadership structure of large aggregated health systems built around an AHC is even more complex and heterogeneous. Yet, to ensure the prosperity of the academic mission, the governance structure of such health care systems is of critical importance. Preservation of academic oversight of the faculty practice plan, a unifying central focal point of organizational decision making, and genuine physician leadership are three overarching governance characteristics that strengthen the prosperity of the academic mission within large aggregated health systems. Despite the heterogeneous nature of academic health system governance, these critical components of organizational leadership structure facilitate support of a robust academic mission. Understanding these principles and objectives of governance is essential for critical faculty engagement in AHC leadership activities.

Governance of Academic Medical Centers Is Indeed a Complex and Unique Operation.

As academic medical centers (AMCs) have extended their operations into their communities, partnered with new organizations, and developed new modes of operation to achieve their missions, new governance approaches are required. Chari and colleagues, in this issue of Academic Medicine, describe the development and application of criteria to evaluate governance options for the University of California (UC), which has a number of public AMCs, almost all of which are components of individual UC universities. Although many of these criteria may also be applicable to smaller AMCs, a more individual approach to governance is required-that is, one must step back and first ask about the organization, structure, and goals of the entities to be governed. The major nonfederal and nonspecialty teaching hospitals in the United States are about evenly split between those that are university owned or controlled and those having an independent relationship with their associated medical school. However, the challenges, obstacles, and desired end points are similar. The development of a successful governance structure will require identifying and appreciating many factors.

Predictors of pregnancy and live birth after insemination in couples with unexplained or male-factor infertility.

OBJECTIVE: To identify risk factors for pregnancy outcomes in couples treated with intracervical or intrauterine insemination, with or without superovulation for unexplained or male-factor infertility. DESIGN: Secondary analysis of data from a randomized superovulation and intrauterine insemination trial. SETTING: Academic medical centers. INTERVENTION(S): Treatment continued for four cycles unless pregnancy was achieved. PATIENT(S): Out of 932 couples randomized to four treatment groups, 664 couples who had completed the lifestyle questionnaires were assessed for occurrence of pregnancy and live birth. MAIN OUTCOME MEASURE(S): Pregnancy and live birth. RESULT(S): The pregnancy and live birth rates were significantly higher in couples in which the female partners reported that they had consumed coffee or tea in the past or drank alcoholic beverages in the past (past users) compared with those who had never consumed coffee, tea, or alcoholic beverages. Past users also had significantly higher pregnancy and live birth rates than those currently consuming coffee or tea or alcoholic beverages. Demographic, occupational exposure, and other lifestyle factors were not significant. CONCLUSION(S): Couples in which the female partners drank coffee, tea, or alcoholic beverages in the past had higher pregnancy and live birth rates compared with never or current users. When discontinuing these habits, they might have made other lifestyle changes to improve the pregnancy outcome.

Randomized trial of leuprolide versus continuous oral contraceptives in the treatment of endometriosis-associated pelvic pain.

OBJECTIVE: To compare the efficacy of leuprolide and continuous oral contraceptives in the treatment of endometriosis-associated pain. DESIGN: Prospective, randomized, double-blind controlled trial. SETTING: Academic medical centers in Rochester, New York, and Boston, Massachusetts. PATIENT(S): Forty-seven women with endometriosis-associated pelvic pain. INTERVENTION(S): Forty-eight weeks of either depot leuprolide, 11.25 mg IM every 12 weeks with hormonal add-back using norethindrone acetate 5 mg orally, daily; or a generic monophasic oral contraceptive (1 mg norethindrone + 35 mg ethinyl estradiol) given daily. MAIN OUTCOME MEASURE(S): Biberoglu and Behrman (B&B) pain scores, numerical rating scores (NRS), Beck Depression Inventory (BDI), and Index of Sexual Satisfaction (ISS). RESULT(S): Based on enrollment of 47 women randomized to continuous oral contraceptives and to leuprolide, there were statistically significant declines in B&B, NRS, and BDI scores from baseline in both groups. There were no significant differences, however, in the extent of reduction in these measures between the groups. CONCLUSION(S): Leuprolide and continuous oral contraceptives appear to be equally effective in the treatment of endometriosis-associated pelvic pain.

Development of an audit method to assess the prevalence of the ACGME's general competencies in an undergraduate medical education curriculum.

BACKGROUND: Despite the use of competency-based frameworks to evaluate physicians, the role of competency-based objectives in undergraduate medical education remains uncertain. PURPOSE: By use of an audit methodology, we sought to determine how the six Accreditation Council for Graduate Medical Education (ACGME) competencies, conceptualized as educational domains, would map onto an undergraduate medical curriculum. METHODS: Standardized audit forms listing required activities were provided to course directors, who were then asked to indicate which of the domains were represented in each activity. Descriptive statistics were calculated. RESULTS: Of 1,500 activities, there was a mean of 2.13 domains per activity. Medical Knowledge was the most prevalent (44%), followed by Patient Care (20%), Interpersonal and Communication Skills (12%), Professionalism (9%), Systems-Based Practice (8%), and Practice-Based Learning and Improvement (7%). There was considerable variation by year and course. CONCLUSIONS: The domains provide a useful framework for organizing didactic components. Faculty can also consider activities in light of the domains, providing a vocabulary for instituting curricular change and innovation.

Is a history of gestational diabetes related to risk factors for coronary heart disease?

Coronary heart disease (CHD) risk in 20 non-diabetic women with and 20 without a distant history of gestational diabetes (hGDM), matched on age, body mass index, and time since GDM-affected pregnancy, was compared in a case control study. Women with an hGDM had lower high-density lipoprotein cholesterol (HDL-c), p = .02, and higher triglycerides, p < or = .001, versus controls. The combination of high triglycerides and low HDL-c occurred in 25% of hGDM cases versus 0% of controls, p

The economics of new faculty hires in basic science.

PURPOSE: To compare the streams of expenses and revenues associated with investment in a cohort of basic science investigators at the University of Rochester School of Medicine & Dentistry for seven years. METHOD: The authors evaluated a medical school's financial investment in 25 basic science faculty who were hired between 1999 and 2004 to expand basic science research. The authors compared direct and indirect costs with the extramural grant support generated by these investigators through 2006. To facilitate a comparison of investments made and grants generated, the authors calculated present value (in 2006 dollars) of revenues and expenses using the school's approximate cost of capital. RESULTS: Of the 25 faculty members hired, 24 (96%) remained at the school through 2006. From 1999 to 2006, the school invested a total of $69.0 million ($33.1 million in start-up costs and $35.9 million in indirect costs) to support the faculty members. Through 2006, these faculty members generated $99.7 million in extramural grant revenue ($70.7 million in direct grant revenue and $29.1 million in indirect grant revenue). Whereas the faculty generated $1.45 in total grant revenue per dollar invested, start-up expenses and incomplete recovery of indirect costs required the school to add 40 cents to every grant dollar generated to achieve financial equilibrium. CONCLUSIONS: Investments in basic science research, even when successful, may require significant financial subsidies from academic health centers.

Prevalence of metabolic syndrome and related characteristics in obese adolescents with and without polycystic ovary syndrome.

CONTEXT: Adults with polycystic ovary syndrome (PCOS) may be at increased risk for metabolic syndrome (MBS) and related cardiovascular disease. It is not clear whether PCOS diagnosed in adolescence increases the risk of MBS in this age group. OBJECTIVE: The aim was to compare the prevalence and related characteristics of MBS in obese adolescents with and without PCOS. DESIGN: We conducted a cross-sectional study of overweight and obese PCOS adolescents and BMI matched controls. PATIENTS AND PARTICIPANTS: A total of 74 subjects, 43 with PCOS and 31 controls, participated in the study. INTERVENTIONS: Each subject underwent a physical examination and laboratory evaluation for a diagnosis of MBS. Regional fat distribution was determined by computerized tomography scan in the PCOS adolescents. MAIN OUTCOME MEASURES: We measured the prevalence of MBS and its components in adolescent subjects and controls. RESULTS: The PCOS group had larger ovarian volume and higher measures of total testosterone and free androgen index than controls, but there were no differences in waist circumference, fasting glucose, blood pressure, or lipids. PCOS adolescents demonstrated more glucose abnormalities and higher plasminogen activator inhibitor-1. By pediatric criteria, 53% of the PCOS and 55% of the control adolescents had MBS. By adult criteria, 26% of PCOS and 29% of controls met diagnostic criteria for MBS. CONCLUSIONS: Obese adolescent women have a high prevalence of MBS, and PCOS does not add additional risk for MBS. There appears to be an association between MBS and visceral adiposity. PCOS is associated with increased incidence of glucose intolerance and increased plasminogen activator inhibitor-1. Our results reinforce the importance of obesity counseling in adolescents to recognize the possible risk of future cardiovascular disease in these young women.

The impact of metformin, oral contraceptives, and lifestyle modification on polycystic ovary syndrome in obese adolescent women in two randomized, placebo-controlled clinical trials.

CONTEXT: Polycystic ovary syndrome (PCOS) presents in adolescence, and obesity is a common finding. The benefits and risks of alternate approaches to the management of PCOS in obese adolescent women are not clear. OBJECTIVE: We investigated the effects of metformin, oral contraceptives (OCs), and/or lifestyle modification in obese adolescent women with PCOS. DESIGN: Two small, randomized, placebo-controlled clinical trials were performed. PATIENTS AND PARTICIPANTS: A total of 79 obese adolescent women with PCOS participated. INTERVENTIONS: In the single treatment trial, subjects were randomized to metformin, placebo, a lifestyle modification program, or OC. In the combined treatment trial, all subjects received lifestyle modification and OC and were randomized to metformin or placebo. MAIN OUTCOME MEASURES: Serum concentrations of androgens and lipids were measured. RESULTS: Lifestyle modification alone resulted in a 59% reduction in free androgen index with a 122% increase in SHBG. OC resulted in a significant decrease in total testosterone (44%) and free androgen index (86%) but also resulted in an increase in C-reactive protein (39.7%) and cholesterol (14%). The combination of lifestyle modification, OC, and metformin resulted in a 55% decrease in total testosterone, as compared to 33% with combined treatment and placebo, a 4% reduction in waist circumference, and a significant increase in HDL (46%). CONCLUSIONS: In these preliminary trials, both lifestyle modification and OCs significantly reduce androgens and increase SHBG in obese adolescents with PCOS. Metformin, in combination with lifestyle modification and OC, reduces central adiposity, reduces total testosterone, and increases HDL, but does not enhance overall weight reduction.

Ovulation induction management of PCOS.

Ovulation induction is the principal infertility treatment for women with polycystic ovarian syndrome (PCOS). Among PCOS patients who are overweight or obese, weight loss is the most physiologic method of inducing ovulation. For women in whom weight loss is not possible, or for lean women with PCOS, clomiphene citrate is an effective first-line method of ovulation induction. In clomiphene-resistant women, alternative treatments include adjunctive metformin or dexamethasone, aromatase inhibitors, or ovarian drilling. If there is no pregnancy despite several cycles of successful ovulation induction, gonadotropin treatment should be considered, in which case in vitro fertilization is recommended as the safest and most effective strategy.