Translating Science into Sound Clinical Practice ContemporaryOBGYN.net BSO: Solving the risk/benefit equation Choosing candidates, monitoring outcomes Fetal U/S: How to Put Safety First VOLUME 56, NUMBER 7 Is ‘Progress’ Good for Your Practice? 7 Ways to Avoid an Ob/Gyn Shortage JULY 2011 PREMARIN® (CONJUGATED ESTROGENS) VAGINAL CREAM BRIEF SUMMARY: See Package Insert for Full Prescribing Information. For further product information and current package insert, please visit www.premarinvaginalcreamhcp.com or call our medical communications department toll-free at 1-800-934-5556. WARNING: CARDIOVASCULAR DISORDERS, ENDOMETRIAL CANCER, BREAST CANCER and PROBABLE DEMENTIA ESTROGEN-ALONE THERAPY ENDOMETRIAL CANCER There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding [see Warnings and Precautions (5.3)]. CARDIOVASCULAR DISORDERS AND PROBABLE DEMENTIA Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia [see Warnings and Precautions (5.2, 5.4), and Clinical Studies (14.2, 14.3) in full prescribing information]. The Women’s Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg], relative to placebo [see Warnings and Precautions (5.2), and Clinical Studies (14.2) in full prescribing information]. The WHI Memory Study (WHIMS) estrogen alone ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with daily CE (0.625 mg) alone, relative to placebo. It is unknown whether this ﬁnding applies to younger postmenopausal women [see Warnings and Precautions (5.4), Use in Speciﬁc Populations (8.5), and Clinical Studies (14.3) in full prescribing information]. In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and other dosage forms of estrogens. Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman. ESTROGEN PLUS PROGESTIN THERAPY CARDIOVASCULAR DISORDERS AND PROBABLE DEMENTIA Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia [see Warnings and Precautions (5.2, 5.4), and Clinical Studies (14.2, 14.3) in full prescribing information]. The WHI estrogen plus progestin substudy reported increased risks of DVT, pulmonary embolism, stroke and myocardial infarction in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral CE (0.625 mg) combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo [see Warnings and Precautions (5.2), and Clinical Studies (14.2) in full prescribing information]. The WHIMS estrogen plus progestin ancillary study of the WHI, reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this ﬁnding applies to younger postmenopausal women [see Warnings and Precautions (5.4), Use in Speciﬁc Populations (8.5), and Clinical Studies (14.3) in full prescribing information]. BREAST CANCER The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer [see Warnings and Precautions (5.3), and Clinical Studies (14.2) in full prescribing information]. In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA, and other combinations and dosage forms of estrogens and progestins. Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman. INDICATIONS AND USAGE Treatment of Atrophic Vaginitis and Kraurosis Vulvae Treatment of Moderate to Severe Dyspareunia, a Symptom of Vulvar and Vaginal Atrophy, due to Menopause CONTRAINDICATIONS PREMARIN Vaginal Cream therapy should not be used in women with any of the following conditions: • Undiagnosed abnormal genital bleeding • Known, suspected, or history of breast cancer • Known or suspected estrogen-dependent neoplasia • Active deep vein thrombosis, pulmonary embolism or a history of these conditions • Active arterial thromboembolic disease (for example, stroke, and myocardial infarction), or a history of these conditions • Known liver dysfunction or disease • Known thrombophilic disorders • Known or suspected pregnancy WARNINGS AND PRECAUTIONS Risks From Systemic Absorption Systemic absorption occurs with the use of PREMARIN Vaginal Cream. The warnings, precautions, and adverse reactions associated with oral PREMARIN treatment should be taken into account. Cardiovascular Disorders An increased risk of stroke and deep vein thrombosis (DVT) has been reported with estrogen-alone therapy. An increased risk of pulmonary embolism, DVT, stroke and myocardial infarction has been reported with estrogen plus progestin therapy. Should any of these occur or be suspected, estrogens with or without progestins should be discontinued immediately. Risk factors for arterial vascular disease (for example, hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (for example, personal history of venous thromboembolism [VTE], obesity, and systemic lupus erythematosus) should be managed appropriately. Stroke In the Women’s Health Initiative (WHI) estrogen-alone substudy, a statistically signiﬁcant increased risk of stroke was reported in women 50 to 79 years of age receiving daily CE (0.625 mg) compared to women in the same age group receiving placebo (45 versus 33 per 10,000 women-years). The increase in risk was demonstrated in year one and persisted [see Clinical Studies (14.2) in full prescribing information]. Should a stroke occur or be suspected, estrogens should be discontinued immediately. Subgroup analyses of women 50 to 59 years of age suggest no increased risk of stroke for those women receiving CE (0.625 mg) versus those receiving placebo (18 versus 21 per 10,000 women-years).1 In the WHI estrogen plus progestin substudy, a statistically signiﬁcant increased risk of stroke was reported in all women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to placebo (33 versus 25 per 10,000 women-years) [see Clinical Studies (14.2) in full prescribing information]. The increase in risk was demonstrated after the ﬁrst year and persisted.1 Coronary Heart Disease In the WHI estrogen-alone substudy, no overall effect on coronary heart disease (CHD) events (deﬁned as nonfatal myocardial infarction [MI], silent MI, or CHD death) was reported in women receiving estrogen-alone compared to placebo [see Clinical Studies (14.2) in full prescribing information].1 Subgroup analyses of women 50 to 59 years of age suggest a statistically non-signiﬁcant reduction in CHD events (CE 0.625 mg compared to placebo) in women with less than 10 years since menopause (8 versus 16 per 10,000 women-years). In the WHI estrogen plus progestin substudy, there was a statistically non-signiﬁcant increased risk of CHD events in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (41 versus 34 per 10,000 women-years).1 An increase in relative risk was demonstrated in year 1, and a trend toward decreasing relative risk was reported in years 2 through 5 [see Clinical Studies (14.2) in full prescribing information]. In postmenopausal women with documented heart disease (n = 2,763), average age 66.7 years, in a controlled clinical trial of secondary prevention of cardiovascular disease (Heart and Estrogen/Progestin Replacement Study [HERS]), treatment with daily CE (0.625 mg) plus MPA (2.5 mg) demonstrated no cardiovascular beneﬁt. During an average follow-up of 4.1 years, treatment with CE plus MPA did not reduce the overall rate of CHD events in postmenopausal women with established coronary heart disease. There were more CHD events in the CE plus MPA-treated group than in the placebo group in year 1, but not during subsequent users. Two thousand, three hundred and twenty-one (2,321) women from the original HERS trial agreed to participate in an open label extension of HERS, HERS II. Average follow-up in HERS II was an additional 2.7 years, for a total of 6.8 years overall. Rates of CHD events were comparable among women in the CE (0.625 mg) plus MPA (2.5 mg) group and the placebo group in HERS, HERS II, and overall. Venous Thromboembolism (VTE) In the WHI estrogen-alone substudy, the risk of VTE (DVT and pulmonary embolism [PE]) was increased for women receiving daily CE (0.625 mg) compared to placebo (30 versus 22 per 10,000 women-years), although only the increased risk of DVT reached statistical signiﬁcance (23 versus 15 per 10,000 women-years). The increase in VTE risk was demonstrated during the ﬁrst 2 years 3 [see Clinical Studies (14.2) in full prescribing information]. Should a VTE occur or be suspected, estrogens should be discontinued immediately. In the WHI estrogen plus progestin substudy, a statistically signiﬁcant 2-fold greater rate of VTE was reported in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (35 versus 17 per 10,000 women-years). Statistically signiﬁcant increases in risk for both DVT (26 versus 13 per 10,000 women-years) and PE (18 versus 8 per 10,000 women-years) were also demonstrated. The increase in VTE risk was observed during the ﬁrst year and persisted 4 [see Clinical Studies (14.2) in full prescribing information]. Should a VTE occur or be suspected, estrogens should be discontinued immediately. If feasible, estrogens should be discontinued at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization. Malignant Neoplasms Endometrial Cancer An increased risk of endometrial cancer has been reported with the use of unopposed estrogen therapy in a woman with a uterus. The reported endometrial cancer risk among unopposed estrogen users is about 2- to 12-fold greater than in non-users, and appears dependent on duration of treatment and on estrogen dose. Most studies show no signiﬁcant increased risk associated with use of estrogens for less than 1 year. The greatest risk appears to be associated with prolonged use, with increased risks of 15- to 24-fold for 5 to 10 years or more, and this risk has been shown to persist for at least 8 to 15 years after estrogen therapy is discontinued. Clinical surveillance of all women using estrogen-alone or estrogen plus progestin therapy is important. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding. There is no evidence that the use of natural estrogens results in a different endometrial risk proﬁle than synthetic estrogens of equivalent estrogen dose. Adding a progestin to postmenopausal estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. In a 52-week clinical trial using PREMARIN Vaginal Cream alone (0.5 g inserted twice weekly or daily for 21 days, then off for 7 days), there was no evidence of endometrial hyperplasia or endometrial carcinoma. Breast Cancer The most important randomized clinical trial providing information about breast cancer in estrogen-alone users is the Women’s Health Initiative (WHI) substudy of daily CE (0.625 mg). In the WHI estrogen-alone substudy, after an average follow-up of 7.1 years, daily CE (0.625 mg) was not associated with an increased risk of invasive breast cancer [relative risk (RR) 0.80] 5 [see Clinical Studies (14.2) in full prescribing information]. The most important randomized clinical trial providing information about breast cancer in estrogen plus progestin users is the WHI substudy of daily CE (0.625 mg) plus MPA (2.5 mg). After a mean follow-up of 5.6 years, the estrogen plus progestin substudy reported an increased risk of breast cancer in women who took daily CE plus MPA. In this substudy, prior use of estrogen-alone or estrogen plus progestin therapy was reported by 26 percent of the women. The relative risk of invasive breast cancer was 1.24, and the absolute risk was 41 versus 33 cases per 10,000 women-years, for estrogen plus progestin compared with placebo.6 Among women who reported prior use of hormone therapy, the relative risk of invasive breast cancer was 1.86, and the absolute risk was 46 versus 25 cases per 10,000 women-years for estrogen plus progestin compared with placebo. Among women who reported no prior use of hormone therapy, the relative risk of invasive breast cancer was 1.09, and the absolute risk was 40 versus 36 cases per 10,000 women-years for estrogen plus progestin compared with placebo. In the same substudy, invasive breast cancers were larger and diagnosed at a more advanced stage in the CE (0.625 mg) plus MPA (2.5 mg) group compared with the placebo group. Metastatic disease was rare, with no apparent difference between the two groups. Other prognostic factors, such as histologic subtype, grade and hormone receptor status did not differ between the groups [see Clinical Studies (14.2) in full prescribing information]. Consistent with the WHI clinical trial, observational studies have also reported an increased risk of breast cancer for estrogen plus progestin therapy, and a smaller increased risk for estrogen-alone therapy, after several years of use. The risk increased with duration of use, and appeared to return to baseline over about 5 years after stopping treatment (only the observational studies have substantial data on risk after stopping). Observational studies also suggest that the risk of breast cancer was greater, and became apparent earlier, with estrogen plus progestin therapy as compared to estrogen-alone therapy. However, these studies have not generally found signiﬁcant variation in the risk of breast cancer among different estrogen plus progestin combinations, doses, or routes of administration. The use of estrogen-alone and estrogen plus progestin therapy has been reported to result in an increase in abnormal mammograms, requiring further evaluation. All women should receive yearly breast examinations by a healthcare provider and perform monthly breast self-examinations. In addition, mammography examinations should be scheduled based on patient age, risk factors, and prior mammogram results. Ovarian Cancer The WHI estrogen plus progestin substudy reported a statistically non-signiﬁcant increased risk of ovarian cancer. After an average follow-up of 5.6 years, the relative risk for ovarian cancer for CE plus MPA versus placebo, was 1.58 (95 percent nCI 0.77-3.24). The absolute risk for CE plus MPA versus placebo was 4 versus 3 cases per 10,000 women-years.7 In some epidemiologic studies, the use of estrogen-only products, in particular for 5 or more years, has been associated with an increased risk of ovarian cancer. However, the duration of exposure associated with increased risk is not consistent across all epidemiologic studies, and some report no association. Probable Dementia In the estrogen-alone Women’s Health Initiative Memory Study (WHIMS), an ancillary study of WHI, a population of 2,947 hysterectomized women 65 to 79 years of age was randomized to daily CE (0.625 mg) or placebo. In the WHIMS estrogen-alone ancillary study, after an average follow-up of 5.2 years, 28 women in the estrogen-alone group and 19 women in the placebo group were diagnosed with probable dementia. The relative risk of probable dementia for CE-alone versus placebo was 1.49 (95 percent nCI 0.83-2.66). The absolute risk of probable dementia for CE-alone versus placebo was 37 versus 25 cases per 10,000 women-years 8 [see Use in Speciﬁc Populations (8.3), and Clinical Studies (14.3) in full prescribing information]. In the WHIMS estrogen plus progestin ancillary study, a population of 4,532 postmenopausal women 65 to 79 years of age was randomized to daily CE (0.625 mg) plus MPA (2.5 mg) or placebo. After an average follow-up of 4 years, 40 women in the CE plus MPA group and 21 women in the placebo group were diagnosed with probable dementia. The relative risk of probable dementia for CE plus MPA versus placebo was 2.05 (95 percent nCI 1.21-3.48). The absolute risk of probable dementia for CE plus MPA versus placebo was 45 versus 22 cases per 10,000 women-years 8 [see Use in Speciﬁc Populations (8.3), and Clinical Studies (14.3) in full prescribing information]. When data from the two populations were pooled as planned in the WHIMS protocol, the reported overall relative risk for probable dementia was 1.76 (95 percent nCI 1.19-2.60). Since both substudies were conducted in women 65 to 79 years of age, it is unknown whether these ﬁndings apply to younger postmenopausal women8 [see Use in Speciﬁc Populations (8.5), and Clinical Studies (14.3) in full prescribing information]. Gallbladder Disease A 2- to 4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported. Hypercalcemia Estrogen administration may lead to severe hypercalcemia in women with breast cancer and bone metastases. If hypercalcemia occurs, use of the drug should be stopped and appropriate measures taken to reduce the serum calcium level. (continued on next page) Visual Abnormalities Retinal vascular thrombosis has been reported in patients receiving estrogens. Discontinue medication pending examination if there is sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine. If examination reveals papilledema or retinal vascular lesions, estrogens should be permanently discontinued. Addition of a Progestin When a Woman Has Not Had a Hysterectomy Studies of the addition of a progestin for 10 or more days of a cycle of estrogen administration or daily with estrogen in a continuous regimen have reported a lowered incidence of endometrial hyperplasia than would be induced by estrogen treatment alone. Endometrial hyperplasia may be a precursor to endometrial cancer. There are, however, possible risks that may be associated with the use of progestins with estrogens compared to estrogen-alone regimens. These include an increased risk of breast cancer. Elevated Blood Pressure In a small number of case reports, substantial increases in blood pressure have been attributed to idiosyncratic reactions to estrogens. In a large, randomized, placebo-controlled clinical trial, a generalized effect of estrogen therapy on blood pressure was not seen. Hypertriglyceridemia In patients with pre-existing hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis. Consider discontinuation of treatment if pancreatitis occurs. Hepatic Impairment and/or Past History of Cholestatic Jaundice Estrogens may be poorly metabolized in women with impaired liver function. For women with a history of cholestatic jaundice associated with past estrogen use or with pregnancy, caution should be exercised, and in the case of recurrence, medication should be discontinued. Hypothyroidism Estrogen administration leads to increased thyroid-binding globulin (TBG) levels. Women with normal thyroid function can compensate for the increased TBG by making more thyroid hormone, thus maintaining free T4 and T3 serum concentrations in the normal range. Women dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of their thyroid replacement therapy. These women should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range. Fluid Retention Estrogens may cause some degree of ﬂuid retention. Patients with conditions that might be inﬂuenced by this factor, such as cardiac or renal dysfunction, warrant careful observation when estrogens are prescribed. Hypocalcemia Estrogens should be used with caution in individuals with hypoparathyroidism as estrogen-induced hypocalcemia may occur. Exacerbation of Endometriosis A few cases of malignant transformation of residual endometrial implants have been reported in women treated post-hysterectomy with estrogen-alone therapy. For women known to have residual endometriosis posthysterectomy, the addition of progestin should be considered. Angioedema Exogenous estrogens may induce or exacerbate symptoms of angioedema, particularly in women with hereditary angioedema. Exacerbation of Other Conditions Estrogen therapy may cause an exacerbation of asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas and should be used with caution in women with these conditions. Effects on Barrier Contraception PREMARIN Vaginal Cream exposure has been reported to weaken latex condoms. The potential for PREMARIN Vaginal Cream to weaken and contribute to the failure of condoms, diaphragms, or cervical caps made of latex or rubber should be considered. Laboratory Tests Serum follicle stimulating hormone and estradiol levels have not been shown to be useful in the management of moderate to severe symptoms of vulvar and vaginal atrophy. Drug-Laboratory Test Interactions Accelerated prothrombin time, partial thromboplastin time, and platelet aggregation time; increased platelet count; increased factors II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, II-VII-X complex, and beta-thromboglobulin; decreased levels of antifactor Xa and antithrombin III, decreased antithrombin III activity; increased levels of ﬁbrinogen and ﬁbrinogen activity; increased plasminogen antigen and activity. Increased thyroid-binding globulin (TBG) leading to increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T4 levels (by column or by radioimmunoassay) or T3 levels by radioimmunoassay. T3 resin uptake is decreased, reﬂecting the elevated TBG. Free T4 and free T3 concentrations are unaltered. Women on thyroid replacement therapy may require higher doses of thyroid hormone. Other binding proteins may be elevated in serum, for example, corticosteroid binding globulin (CBG), sex hormone-binding globulin (SHBG), leading to increased total circulating corticosteroids and sex steroids, respectively. Free hormone concentrations, such as testosterone and estradiol, may be decreased. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin). Increased plasma HDL and HDL2 cholesterol subfraction concentrations, reduced LDL cholesterol concentrations, increased triglyceride levels. Impaired glucose tolerance. ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: • Cardiovascular Disorders [see Boxed Warning, Warnings and Precautions (5.2)] • Endometrial Cancer [see Boxed Warning, Warnings and Precautions (5.3)] Clinical Study Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trial of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reﬂect the rates observed in practice. In a 12-week, randomized, double-blind, placebo-controlled trial of PREMARIN Vaginal Cream (PVC), a total of 423 postmenopausal women received at least 1 dose of study medication and were included in all safety analyses: 143 women in the PVC-21/7 treatment group (0.5 g PVC daily for 21 days, then 7 days off), 72 women in the matching placebo treatment group; 140 women in the PVC-2x/wk treatment group (0.5 g PVC twice weekly), 68 women in the matching placebo treatment group. A 40-week, open-label extension followed, in which a total of 394 women received treatment with PVC, including those subjects randomized at baseline to placebo. In this study, the most common adverse reactions * 5 percent are shown below (Table 1) [see Clinical Studies (14.1) in full prescribing information]. Table 1: Number (%) of Patients Reporting Treatment Emergent Adverse Events * 5 Percent Only Treatment Body Systema Adverse Event PVC 21/7 (n=143) Placebo 21/7 (n=72) PVC 2x/wk (n=140) Placebo 2x/wk (n=68) Number (%) of Patients with Adverse Event Any Adverse Event Body As A Whole 95 (66.4) 45 (62.5) 97 (69.3) 46 (67.6) Abdominal Pain Accidental Injury Asthenia Back Pain Headache Infection Pain Cardiovascular System 11 (7.7) 4 (2.8) 8 (5.6) 7 (4.9) 16 (11.2) 7 (4.9) 10 (7.0) 2 (2.8) 5 (6.9) 0 3 (4.2) 9 (12.5) 5 (6.9) 3 (4.2) 9 (6.4) 9 (6.4) 2 (1.4) 13 (9.3) 25 (17.9) 16 (11.4) 4 (2.9) 6 (8.8) 3 (4.4) 1 (1.5) 5 (7.4) 12 (17.6) 5 (7.4) 4 (5.9) Vasodilatation 5 (3.5) 4 (5.6) 7 (5.0) 1 (1.5) Table 1: Number (%) of Patients Reporting Treatment Emergent Adverse Events * 5 Percent Only Digestive System Diarrhea Nausea Musculoskeletal System 4 (2.8) 5 (3.5) 2 (2.8) 4 (5.6) 10 (7.1) 3 (2.1) 1 (1.5) 3 (4.4) Arthralgia Nervous System 5 (3.5) 5 (6.9) 6 (4.3) 4 (5.9) Insomnia Respiratory System 6 (4.2) 3 (4.2) 4 (2.9) 4 (5.9) Cough Increased Pharyngitis Sinusitis Skin And Appendages Urogenital System 0 3 (2.1) 1 (0.7) 12 (8.4) 1 (1.4) 2 (2.8) 3 (4.2) 7 (9.7) 7 (5.0) 7 (5.0) 2 (1.4) 16 (11.4) 3 (4.4) 3 (4.4) 4 (5.9) 3 (4.4) Breast Pain 8 (5.6) 1 (1.4) 4 (2.9) 0 Leukorrhea 3 (2.1) 2 (2.8) 4 (2.9) 6 (8.8) Vaginitis 8 (5.6) 3 (4.2) 7 (5.0) 3 (4.4) a Body system totals are not necessarily the sum of the individual adverse events, since a patient may report two or more different adverse events in the same body system. Postmarketing Experience The following adverse reactions have been reported with PREMARIN Vaginal Cream. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Genitourinary System Abnormal uterine bleeding/spotting, dysmenorrhea/pelvic pain, increase in size of uterine leiomyomata, vaginitis (including vaginal candidiasis), change in cervical secretion, cystitis-like syndrome, application site reactions of vulvovaginal discomfort, (including burning, irritation, and genital pruritus), endometrial hyperplasia, endometrial cancer, precocious puberty, leukorrhea. Breasts Tenderness, enlargement, pain, discharge, ﬁbrocystic breast changes, breast cancer, gynecomastia in males. Cardiovascular Deep venous thrombosis, pulmonary embolism, myocardial infarction, stroke, increase in blood pressure. Gastrointestinal Nausea, vomiting, abdominal cramps, bloating, increased incidence of gallbladder disease. Skin Chloasma that may persist when drug is discontinued, loss of scalp hair, hirsutism, rash. Eyes Retinal vascular thrombosis, intolerance to contact lenses. Central Nervous System Headache, migraine, dizziness, mental depression, nervousness, mood disturbances, irritability, dementia. Miscellaneous Increase or decrease in weight, glucose intolerance, edema, arthralgias, leg cramps, changes in libido, urticaria, anaphylactic reactions, exacerbation of asthma, increased triglycerides, hypersensitivity. Additional postmarketing adverse reactions have been reported in patients receiving other forms of hormone therapy. DRUG INTERACTIONS No formal drug interaction studies have been conducted for PREMARIN Vaginal Cream. Metabolic Interactions In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4, such as St. John’s Wort (Hypericum perforatum) preparations, phenobarbital, carbamazepine, and rifampin, may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding proﬁle. Inhibitors of CYP3A4, such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice, may increase plasma concentrations of estrogens and may result in side effects. USE IN SPECIFIC POPULATIONS Pregnancy PREMARIN Vaginal Cream should not be used during pregnancy [see Contraindications (4)]. There appears to be little or no increased risk of birth defects in children born to women who have used estrogens and progestins as an oral contraceptive inadvertently during early pregnancy. Nursing Mothers PREMARIN Vaginal Cream should not be used during lactation. Estrogen administration to nursing mothers has been shown to decrease the quantity and quality of the breast milk. Detectable amounts of estrogens have been identiﬁed in the breast milk of mothers receiving estrogens. Caution should be exercised when PREMARIN Vaginal Cream is administered to a nursing woman. Pediatric Use PREMARIN Vaginal Cream is not indicated in children. Clinical studies have not been conducted in the pediatric population. Geriatric Use There have not been sufﬁcient numbers of geriatric women involved in clinical studies utilizing PREMARIN Vaginal Cream to determine whether those over 65 years of age differ from younger subjects in their response to PREMARIN Vaginal Cream. The Women’s Health Initiative Study In the Women’s Health Initiative (WHI) estrogen-alone substudy (daily conjugated estrogens 0.625 mg versus placebo), there was a higher relative risk of stroke in women greater than 65 years of age [see Clinical Studies (14.2) in full prescribing information]. In the WHI estrogen plus progestin substudy, there was a higher relative risk of nonfatal stroke and invasive breast cancer in women greater than 65 years of age [see Clinical Studies (14.2) in full prescribing information]. The Women’s Health Initiative Memory Study In the Women’s Health Initiative Memory Study (WHIMS) of postmenopausal women 65 to 79 years of age, there was an increased risk of developing probable dementia in women receiving estrogen-alone or estrogen plus progestin when compared to placebo [see Clinical Studies (14.3) in full prescribing information]. Since both ancillary studies were conducted in women 65 to 79 years of age, it is unknown whether these ﬁndings apply to younger postmenopausal women 8 [see Clinical Studies (14.3) in full prescribing information]. Renal Impairment The effect of renal impairment on the pharmacokinetics of PREMARIN Vaginal Cream has not been studied. Hepatic Impairment The effect of hepatic impairment on the pharmacokinetics of PREMARIN Vaginal Cream has not been studied. OVERDOSAGE Overdosage of estrogen may cause nausea and vomiting, breast tenderness, dizziness, abdominal pain, drowsiness/fatigue, and withdrawal bleeding in women. Treatment of overdose consists of discontinuation of PREMARIN therapy with institution of appropriate symptomatic care. This brief summary is based on PREMARIN Vaginal Cream Prescribing Information W10413C022 ET01, Rev 05/10. OUR MISSION Contemporary OB/GYN, a peer-reviewed journal, translates key advances in the specialty into excellence in day-to-day practice. It combines contemporary critical thinking from top academic physicians and evidencebased insights from eminent clinicians into expert articles that are concise, thorough, and compellingly illustrated. EDITORIAL DAN SCHWARTZ Director of Editorial PATRICIA M FERNBERG Editor 440-891-2757 pfernberg@advanstar.com CATHERINE M RADWAN Senior Editor 440-891-2636 cradwan@advanstar.com LISA A HACK MARIAN FREEDMAN Contributing Editors ART & PRODUCTION PETER SELTZER Group Art Director ROBERT M c GARR Group Art Director QUINN WILLIAMS Art Director TERRI JOHNSTONE Sr. Production Manager SALES & MARKETING KEN SYLVIA Vice President, Group Publisher ksylvia@advanstar.com 732-346-3017 AVIVA BELSKY Publisher abelsky@advanstar.com 732-346-3044 BILL SMITH Sales Manager bsmith@advanstar.com 440-891-2718 JACQUELINE MORAN Account Executive, Classifieds 440-891-2762 jmoran@advanstar.com MAUREEN CANNON Permissions/International Licensing mcannon@advanstar.com JOANNA SHIPPOLI Account Executive, Recruitment jshippoli@advanstar.com RENEE SCHUSTER List Account Executive rschuster@advanstar.com EDITOR IN CHIEF CHARLES J LOCKWOOD, MD, MHCM Anita O’Keeffe Young Professor of Women’s Health and Chair, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT EDITORIAL BOARD JONATHAN S BEREK, MD, MMS PAULA J ADAMS HILLARD, MD Professor and Chair, Department of Obstetrics and Gynecology, Stanford University School of Medicine; Director, Women’s Cancer Center, Stanford Cancer Center, Stanford, CA Professor, Department of Obstetrics and Gynecology, Chief, Division of Gynecologic Specialties, Stanford University School of Medicine, Stanford, CA JOSHUA A COPEL, MD SARAH J KILPATRICK, MD, PHD Professor, Obstetrics, Gynecology, and Reproductive Sciences, and Pediatrics, Yale University School of Medicine, New Haven, CT Chair, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA JOHN O L DELANCEY, MD SHARON T PHELAN, MD Norman F Miller Professor of Gynecology, Director, Pelvic Floor Research, Group Director, Fellowship in Female Pelvic Medicine and Reconstructive Surgery, University of Michigan Medical School, Ann Arbor, MI Professor, Department of Obstetrics and Gynecology, University of New Mexico, Albuquerque, NM MARA J DINSMOOR, MD, MPH ELIZABETH E PUSCHECK, MD, MS, CCD Clinical Professor, Department of Obstetrics and Gynecology, NorthShore University HealthSystem, University of Chicago, Pritzker School of Medicine, Evanston, IL VICTORIA L GREEN, MD, MBA, JD Associate Professor, Department of Gynecology and Obstetrics, Emory University, Atlanta, GA FOUNDING EDITOR JOHN T QUEENAN, MD Professor of Obstetrics and Gynecology, Georgetown University School of Medicine, Washington, DC REPRINT SERVICES 800-290-5460, ext. 100 AdvanstarReprints@theYGSgroup.com AUDIENCE DEVELOPMENT JOE MARTIN Audience Development Manager jmartin@advanstar.com CHRISTINE SHAPPELL Audience Development Director 201-391-2359 or 201-240-0867 cshappell@advanstar.com Chair, Dept. of Obstetrics and Gynecology, Wayne State University School of Medicine, Specialist-in-Chief, Detroit Medical Center, Detroit, MI Chief Executive Officer JOSEPH LOGGIA Executive Vice President, Chief Administrative Officer TOM EHARDT Executive Vice President, Chief Marketing Officer STEVE STURM Executive Vice President, Finance and Chief Financial Officer TED ALPERT Executive Vice President GEORGIANN DECENZO Executive Vice President ERIC LISMAN Vice President, Information Technology J VAUGHN Vice President, Media Operations FRANCIS HEID Vice President, Human Resources NANCY NUGENT Vice President, General Counsel WARD D HEWINS Executive Vice President DANNY PHILLIPS Executive Vice President CHRIS DEMOULIN Executive Vice President RON WALL JOE LEIGH SIMPSON, MD Executive Associate Dean for Academic Affairs, Professor of Obstetrics and Gynecology, and Human and Molecular Genetics, Florida International University College of Medicine, Miami, FL EDITORIAL BOARD MEMBERS EMERITUS ANDREW BERCHUCK, MD NICOLETTE S HORBACH, MD RALPH M RICHART, MD NANETTE F SANTORO, MD LEON SPEROFF, MD ADDRESS EDITORIAL AND BUSINESS CORRESPONDENCE to CONTEMPORARY OB/GYN, 24950 Country Club Boulevard, Suite 200, North Olmsted, OH 44070 MAIN NUMBERS: 440-243-8100 or 800-225-4569 DIRECT REPRINT REQUESTS: 800-290-5460, ext. 100; International: 717-505-9701, ext. 100; e-mail: AdvanstarReprints@theYGSgroup.com CUSTOMER SERVICE: 877-922-2022, or write: Circulation Dept, Advanstar Communications Inc, 131 West 1st Street, Duluth, MN 55802 CLASSIFIED ADVERTISING: 800-225-4569 Advanstar Communications Inc. provides certain customer contact data (such as customers’ name, addresses, phone numbers, and e-mail addresses) to third parties who wish to promote relevant products, services, and other opportunities that may be of interest to you. If you do not want Advanstar Communications Inc. to make your contact information available to third parties for marketing purposes, simply call toll-free 866-529-2922 between the hours of 7:30 a.m. and 5 p.m. CST and a customer service representative will assist you in removing your name from Advanstar’s lists. Outside the U.S., please phone 218-740-6477. CONTEMPORARY OB/GYN does not verify any claims or other information appearing in any of the advertisements contained in the publication, and cannot take responsibility for any losses or other damages incurred by readers in reliance on such content. CONTEMPORARY OB/GYN cannot be held responsible for the safekeeping or return of unsolicited articles, manuscripts, photographs, illustrations, or other materials. Library Access Libraries offer online access to current and back issues of CONTEMPORARY OB/GYN through the EBSCO host databases. To subscribe, call toll-free 877-527-7008. Outside the U.S. call 218-740-6477. JULY 2011 CONTEMPORARY OB/GYN 3 JULY 2011 CONTEMPORARYOBGYN.NET VOL. 56, NO. 7 Translating Science into Sound Clinical Practice GRAND ROUNDS 20 BSO: Solving the risk/beneﬁt equation WILLIAM H PARKER, MD Prophylactic bilateral salpingo-oophorectomy at the time of hysterectomy confers long-term health benefits for many women. Success lies in careful candidate selection and monitoring of outcomes. CLINICIAN TO CLINICIAN Is “progress” good for your practice? ALLAN J JACOBS, MD, JD Although advancements in science allow us to better treat patients, the industrialization and bureaucratization of medicine have diminished our status, job satisfaction, and income. Is there a middle ground? 36 Fetal U/S: How to put safety first LAURA HOUSTON, MD ROGER NEWMAN, MD Understanding potential risks and key safety issues associated with fetal ultrasound is the foundation for optimal use of this important imaging modality. 44 An evolving specialty confronts workforce changes ERIN E TRACY, MD, MPH WILLIAM F RAYBURN, MD, MBA 20 NEWSLINE 14 8 10 EDITORIAL CHARLES J LOCKWOOD, MD, MHCM Industrialization of medicine: Coming soon to a practice like yours! 16 CLINICAL INSIGHTS ■ Increasing calcium intake does not further reduce fracture risk LETTERS TO THE EDITOR LEGALLY SPEAKING DAWN COLLINS, JD A retained sponge following hysterectomy raises the question of who was negligent. 51 56 CLASSIFIED AD INDEX Changing workforce needs and expectations have brought about an impending shortage of ob/gyns. But with challenges come solutions, and initiating a dialogue is the first step toward finding them. CONTEMPORARY OB/GYN (Print ISSN#0090-3159, DIGITAL ISSN#2150-6264), is published monthly by Advanstar Communications, Inc, 131 West First St, Duluth, MN 55806-2065. One-year subscription rates: $110.00 per year (USA and Possessions); $140.00 per year (elsewhere). Single copies (prepaid only) $12.00 in the USA; $18.00 per copy elsewhere. Include $6.50 per order plus $2.00 for US postage and handling. Periodicals postage paid at Duluth, MN 55806 and additional mailing offices. POSTMASTER: Please send address changes to Contemporary OB/GYN, PO Box 6084, Duluth, MN 55806-6084. Return Undeliverable Canadian Addresses to: Pitney Bowes, PO Box 25542, London, ON N6C 6B2, CANADA. Canadian GST number: R-124213133RT001. Publications Mail Agreement Number 40612608. Printed in USA. Subscription inquiries/address changes: toll-free 888-527-7008, or dial direct 218-740-6477. ©2011 Advanstar Communications Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including by photocopy, recording, or information storage and retrieval without permission in writing from the publisher. Authorization to photocopy items for internal/educational or personal use, or the internal/educational or personal use of specific clients is granted by Advanstar Communications Inc for libraries and other users registered with the Copyright Clearance Center, 222 Rosewood Dr, Danvers, MA 01923, 978-750-8400 fax 978-646-8700 or visit http://www. copyright.com online. For uses beyond those listed above, please direct your written request to Permission Dept, fax 440-756-5255 or email: mcannon@advanstar.com. 4 CONTEMPORARYOBGYN.NET JULY 2011 COVER ILLUSTRATION BY CHRISTY KRAMES, MA, CMI (TOP); CULTURA/I LOVE IMAGES/GETTY IMAGES(BOTTOM) 28 Have you heard? Contemporary OB/GYN Newsline is a FREE weekly e-newsletter for OB/GYNs and staff, delivering practical and timely specialty information and updates. Breaking Industry News Regulatory Updates Practice Management Tips ! y a d o t p u n Sig ContemporaryOBGYN.net/enewssignup Translating Science into Sound Clinical Practice ONLINE Part of the Your guide to what’s happening online at Contemporary OBGYN.net Y Contemporary OB/GYN is part of the ModernMedicine Network, a Web-based portal for health professionals oﬀering best-in-class content and tools in a rewarding and easy-to-use environment for knowledge-sharing among members of our community. Learn more about averting maternal erythroblastosis and improving fetal outcomes: HTTP://CONTEMPORARYOBGYN.NET/ HEMOLYTIC FREE barcode scanning at www.i-nigma.mobi To join the conversation, use your smartphone and scan the QR code, or go to: HTTP://CONTEMPORARYOBGYN.NET/INCENTIVES Offer your patients with GERD this downloadable, printable list of tips for managing reflux: View a robot-assisted hysterectomy recorded at University Hospitals Case Medical Center in Cleveland HTTP://CONTEMPORARYOBGYN.NET/GERD HTTP://CONTEMPORARYOBGYN.NET/ROBOT THE TOP 7 HIT LIST 3FX, 3D LIFE SCIENCE ANIMATION & EFFECTS (TOP LEFT); BRAND X PICTURES/STEVE ALLEN/GETTY IMAGES (BOTTOM LEFT); LIFESIZE/NISIAN HUGHES/GETTY IMAGES (BOTTOM RIGHT) Dr Joshua Copel blogs about incentives for med students to become primary care providers. 1 Endometrial ablation superior in controlling heavy menses 3 Endometrial ablation is less likely than hysterectomy to lead to later pelvic ﬂoor repair or surgery for urinary incontinence. The top ob/gyn clinical and practice management resources from ModernMedicine.com 6 Preop progesterone helps some BRCA patients Progesterone before breast cancer surgery provides a beneﬁt to women with node-positive disease, a randomized clinical trial shows. 2 Valproate in pregnant women may dramatically worsen the risk of fetal malformation. contemporaryobgyn.net/valproate 4 7 VAP-1 predicts mortality in patients with type 2 diabetes The level of serum vascular adhesion protein-1 can predict the 10-year mortality risk in patients with type 2 diabetes. contemporaryobgyn.net/VAP 5 People who get plenty of omega-3 fatty acids in their diets may have a lower risk for type 2 diabetes. contemporaryobgyn.net/Omega-3 contemporaryobgyn.net/node-pos contemporaryobgyn.net/ablate Fetal risks differ among anticonvulsant combos Omega-3 fats linked to lower diabetes risk Abuse-resistant painkiller gets FDA nod The FDA has approved a pain drug designed to combat the widespread abuse of opioidbased painkillers. contemporaryobgyn.net/Oxecta Early ART reduces HIV transmission risk Starting oral antiretroviral therapy early in those with HIV substantially reduces their risk of transmitting the virus to uninfected sexual partners. contemporaryobgyn.net/antiretroviral LEARN WHAT YOU’RE MISSING: Our online digital editions let you ﬂip through the pages of your favorite Advanstar Communications publications from any computer. Sign up free at the following Web sites: Contemporary Pediatrics: ContemporaryPediatrics.com/digital Medical Economics: memag.com/digital Formulary: formularyjournal.modernmedicine.com/digital Managed Healthcare Executive: managedhealthcareexecutive.com/digital JULY 2011 Drug Topics: drugtopics.com/digital CONTEMPORARY OB/GYN 7 17OHP benefits prior preterm birth patients Dr Charles Lockwood, one of the foremost authorities on preterm birth, has written a balanced and factual editorial laying out his view of progestin use today and in the future.1 However, although his editorial speculates that vaginal progesterone might eventually replace hydroxyprogesterone caproate (17OHP) for reducing the risk of preterm birth, he still recommends 17OHP to treat prior preterm birth patients. Why this apparent contradiction? Te most obvious reason to recommend 17OHP is that current evidence demonstrates that vaginal progesterone is ineﬀective for patients with a prior preterm birth, but shows benefit for short cervix patients. The da Fonseca study using vaginal suppositories was only positive when an analysis excluding many patients was performed2 and a second, larger study using vaginal gel was negative.3 Te 2 prospective studies in which vaginal progesterone showed beneﬁt enrolled women with a short cervix, which represents only about 2% of pregnant women.4,5 Recent literature has documented the risks of serious neonatal morbidity in late preterm births. Hydroxyprogesterone caproate in the National Institute of Child Health and Human Development (NICHD) study6 is the only progestin shown to reduce the number of preterm births (deﬁned as less than 37 weeks). Vaginal progesterone shifed early preterm births to late preterm births. Both the da Fonseca and O’Brien prior preterm birth studies showed no diﬀerence at less than 37 weeks when analyzed using the intent-to-treat principle.2,3 Te short cervix studies either did not report data afer 34 weeks4 or showed no diﬀerence at less than 37 weeks.5 Further, a subanalysis of short-cervix patients in the DeFranco study showed no diﬀerence at less than 37 weeks.7 Terefore, no evidence currently exists that vaginal progesterone has any impact on late preterm birth, which represents the majority of preterm births. Only the NICHD study of 17OHP demonstrates benefit for prior preterm birth patients at early and late gestational ages.6 Tus, the real progestin story is that vaginal progesterone has an important role for short-cervix patients but is unlikely to replace 17OHP for prior preterm birth patients in the foreseeable future. ROBERT BIRCH, PHD DIRECTOR, CLINICAL SCIENCES KV PHARMACEUTICAL COMPANY 2. da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study. Am J Obstet Gynecol. 2003;188(2):419-424. 3. O’Brien JM, Adair CD, Lewis DF, et al. Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebocontrolled trial. Ultrasound Obstet Gynecol. 2007;30(5):687-696. 4. Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH; Fetal Medicine Foundation Second Trimester Screening Group. Progesterone and the risk of preterm birth among women with a short cervix. N Engl J Med. 2007;357(5):462-469. 5. Hassan SS, Romero R, Vidyadhari D, et al. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. April 6, 2011. Epub ahead of print. 6. Meis PJ, Klebanoff M, Thom E, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003;348(24):2379-2385. Erratum in: N Engl J Med. 2003:349(13):1299. 7. DeFranco EA, O’Brien JM, Adair CD, et al. Vaginal progesterone is associated with a decrease in risk for early preterm birth and improved neonatal outcome in women with a short cervix: a secondary analysis from a randomized, double-blind, placebocontrolled trial. Ultrasound Obstet Gynecol. 2007;30(5):697-705. Dr Lockwood responds: Tank you for your interest in my editorial. However, I see no contradiction. I recommend vaginal progesterone for incidentally found short cervices in women without prior preterm births and 17 hydroxyprogesterone (17OHP) in women with prior spontaneous preterm births. As I concluded: “Because the Hassan et al study was underpowered to conﬁrm whether cervical length screening and vaginal progesterone therapy reduced preterm births in previously aﬀected women, and because a prior study by O’Brien and colleagues failed to demonstrate that progesterone 90 mg vaginal gel reduced recurrent preterm birth before 33 weeks among such women, I would still recommend treating patients with singleton gestations and a prior spontaneous preterm delivery with weekly intramuscular injections of 17OHP obtained from the least expensive available and reliable source.” I then go on to speculate: “For these high-risk women, additional studies are needed to determine whether sonographic cervical screening with vaginal progesterone is more cost eﬀective than prophylactic 17OHP therapy. In addition, cerclage may be indicated in such women who are found to have shortened cervices prior to 23 weeks. However, if some combination of cerclage and/or vaginal progesterone produces comparable or better rates of prematurity prevention, 17OHP therapy can be abandoned once again.” Tus, I fail to see any contradiction. Again, thanks for your interest. All the best, REFERENCES CHARLES J LOCKWOOD, MD, MHCM 1. Lockwood CJ. The real progesterone story. Contemp OB/GYN. 2011;56(5):10-15. EDITOR IN CHIEF, CONTEMPORARY OB/GYN 8 CONTEMPORARYOBGYN.NET JULY 2011 A ! F D ed v ow ro N pp A Knowing the Risk Matters You know that HPV causes cervical cancer. You know that identifying the disease early helps improve patient management decisions—and outcomes. But is pooled hrHPV testing enough? Consider these facts: s HPV genotypes 16 and 18 together account for nearly 70% of diagnosed cervical cancers. s In the ATHENA Study using the cobas® HPV Test, 1 in 10 women age 30 years and older who tested positive for HPV 16 and/or 18, actually had cervical precancer, even though they had a normal pap result. s The cobas® HPV Test is the only assay that provides speciﬁc genotyping information for HPV genotypes 16 and 18, while simultaneously reporting the 12 other high-risk HPV types as a pooled result, so you can know more about ‚ your patient s risk for cervical cancer. Call your Roche Molecular Diagnostics Representative today or visit www.hpv1618.info to ﬁnd out more. COBAS and LIFE NEEDS ANSWERS are trademarks of Roche. © 2011 Roche Diagnostics. All rights reserved. 472-50537-0411 The cobas® HPV Test gives you the power to know more about your patients risk for cervical cancer BY CHARLES J LOCKWOOD, MD, MHCM Industrialization of medicine: Coming soon to a practice like yours! H ow did it feel to live in New England in the early 19th century and witness the Industrial Revolution? Well, it likely depended upon your perspective. If you were a wealthy mill owner, it must have felt pretty good. If you were a former farmer forced oﬀ your land by plummeting food prices and now needing to work long hours in that mill for pennies a day, probably not so good. Today we face the industrialization of medicine and, again, how physicians feel about it may depend upon our perspective. If you are a Generation Y member seeking a fuller life outside medicine, the future is bright. If you are a 60-something solo practitioner who has worked 70-hour weeks for 35 years, the future might not seem quite so bright. How did we get into this situation? I have pointed out on these pages a number of times that the United States expends up to 100% more than other industrialized nations for healthcare but is ranked only 37th in healthcare performance by the World Health Organization.1 Despite Data on the care you provide spending more than 17% of our could be made public under a GDP on healthcare, Americans proposed rule. Find out more: contemporaryobgyn.net/ receive about half of the performance recommended preventive care.2 Conversely, while Medicare spending patterns vary substantially among regions, higher spending is not associated with better outcomes, higher patient satisfaction, or improved access to care.3 Worse, preventable errors add billions to our collective healthcare bill.4 Arguing that a relentlessly rising volume of care driven by our discounted fee-for-service payment system is exacerbating both cost inﬂation and suboptimal WE WANT TO HEAR FROM YOU 10 Send your feedback to: DrLockwood@advanstar.com. CONTEMPORARYOBGYN.NET JULY 2011 care, the Centers for Medicare and Medicaid Services (CMS) has decided to adopt value-based purchasing (VBP).5 In brief, the CMS hospital VBP program will aﬀect inpatient Medicare payments beginning in FY 2013 based on discharges accruing on or afer October 1, 2012. Value-based incentive payments will be made to acute care hospitals, depending on how these hospitals perform on 25 CMS Hospital Compare reporting measures. Tese 25 indices include 17 clinical process-of-care measures (70% of bonus/risk) and 8 HCAHPS patient satisfaction measures (30% of bonus/ risk). Ultimately, higher rates of 30-day readmissions and medical errors will be penalized. While superior performance or solid improvement during a ﬁscal year will yield a higher VBP payment, meeting bonus thresholds will be diﬃcult. Te very best performing hospitals, those in the top 10%, will be eligible for extra compensation from the pool of dollars withheld from the lower performing hospitals.6 Conversely, hospitals with higher-thanaverage 30-day readmission rates for diagnoses such as heart failure and pneumonia will face up to 1% penalties starting in 2013, ramping up to 3% in 2015. To meet these tough targets, hospitals will need to strictly control physician practice. In fact, an astonishing 50% of all physician practices are now owned by hospitals or integrated delivery systems and the number of physicians employed by hospitals has increased 75% since 2000.7 But this strategy is not without risk for hospitals. On average, they lose about $200,000 per year per doctor over the ﬁrst 3 years of physician employment.7 However, hospitals appear more than willing to accept such losses in return for better control of patient access and referrals as well as physician performance. Moreover, if accountable care organizations begin to dominate the market and hospital revenues and expenses span both ambulatory and inpatient environments, the incentive to acquire even marginally performing physician practices will accelerate. INTRODUCING PRENATAL the smarter choice for your patients NOW... THE FIRST COMPLETE OTC PRENATAL VITAMIN WITH 350 MG OF DHA • 350 mg — the highest level of DHA in an OTC prenatal vitamin • Contains life’sDHA™ — an all-natural, plant-based source of Omega-3 DHA that is fish free and is the same brand found in 99% of all U.S. infant formulas • Supports healthy fetal eye and brain development and function* • 100% of the recommended daily dose of folic acid and iron • Economically priced for a 30-day supply — lower than most prescription plan co-pays * These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. The smarter choice life’sDHA™ is a trademark of Martek Biosciences Corporation. ©Amerifit, Inc. 2011. BRPP 6154-1 June 2011 EDITORIAL Conversely, increasingly complex VBP, bundled charges, and capitated payment models will make it harder and harder for smaller physician practices to operate at a proﬁt independent of large organizations. The healthcare industrial revolution During my own residency, most community ob/gyns were in solo practice or in groups of 2 at the most. Such practices generally employed no more than a nurse, receptionist, and a part-time bookkeeper; in short, they were the equivalent of a family farm. Now, as I look around our service at Yale, no POWER POINTS obstetric providers remain in solo practice and most practice Value-based performance will in groups of 5 or more physicians become the standard plus nurse practitioners and/ by which healthcare or midwives. Oﬃce staﬀers providers are judged. are highly specialized in the business side of medicine, with Hospitals and large group practices some dealing only with claims are absorbing solo submission and others focusing practices. on managerial functions that the solo physician used to perform for himself or herself. Also needed are information technology expertise, specialized contracting assistance, and staﬀ to ensure that all physicians are credentialed with each payer. But even these medium sized-practices may not have the economies of scale necessary for optimal contracting, eﬃcient billing, sound practice management, aggressive marketing, and the purchase of ever more expensive equipment. Tus, in Connecticut and across the country many practices now are actively seeking purchase by, or other formal aﬃ liation arrangements with, medical schools and large hospitals. In short, the practice of medicine has become a big and complex business, and hospitals and physicians are looking to each other to help ﬁnd their way through all the tumult. Take-home message What should you expect? Over the next 5 years, I predict that fee-for-service revenues will decline to levels not seen since the late 1990s and commercial payers will increasingly adopt such CMS payment innovations as VBP, bundled (physician and hospital) payments, capitated medical homes, and accountable care payment schemes. T is will accelerate the drive to an increasingly “corporate” healthcare delivery system. Mandated publication of patient outcomes, satisfaction scores, and cost of care will be rolled out to ensure that 12 CONTEMPORARYOBGYN.NET JULY 2011 patients and their insurers seek the most eﬃcacious, timely, safe, and eﬃcient options for care. The inpatient environment will see increasing use of standardized treatment protocols for common diagnoses, fewer choices in OR equipment and supplies, as well as mounting pressure to use fewer diagnostic tests and more cost-effective medications. Over time simple process measures, such as a patient with pneumonia getting antibiotics within 6 hours of presentation, will lose importance and true outcome measures will move to the forefront. Policy decisions will be made centrally, and employed physicians will receive periodic “scorecards” measuring numbers of patients cared for, patient satisfaction, and outcomes. Finally, the cost of providing care will increasingly be taken into consideration, such that physicians who provide the highest quality of care for the lowest cost will gain the most in compensation and vice versa. Some will embrace this brave new world; others will choose to retire. It will all depend on their perspective. DR LOCKWOOD, editor in chief, is the Anita O’Keeffe Young Professor of Women’s Health and Chair, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut. REFERENCES 1. World Health Organization. WHO World Health Report. The World Health Organization’s ranking of the world’s health systems. Published 2000. http://www.photius.com/rankings/healthranks.html. Accessed May 15, 2011. 2. McGlynn EA, Asch SM, Adams J, et al. The quality of health care delivered to adults in the United States. N Engl J Med. 2003;348(26):2635-2645. 3. Fisher ES, Wennberg DE, Stukel TA, Gottlieb DJ, Lucas FL, Pinder EL. The implications of regional variations in Medicare spending. Part 2: health outcomes and satisfaction with care. Ann Intern Med. 2003;138(4): 288-298. 4. Porter ME, Teisberg EO. Redefining Health Care: Creating ValueBased Competition on Results. Boston, Massachusetts: Harvard Business School Press; 2006. 5. US Department of Health and Human Services. Centers for Medicare and Medicaid Services. Medicare program; hospital inpatient value-based purchasing program. 45 CFR Parts 422 and 480. Final rule (May 6, 2011). Federal Register. 2011;76(88):26490-26547. 6. US Department of Health and Human Services. Centers for Medicare and Medicaid Services. Medicare program; hospital inpatient value-based purchasing program. 45 CFR Parts 422 and 480. Proposed rules (January 13, 2011). Federal Register. 2011;76(9):2454-2491. http://www.gpo.gov/ fdsys/pkg/FR-2011-01-13/pdf/2011-454.pdf. Accessed June 14, 2011. 7. Kocher R, Sahni NR. Hospitals’ race to employ physicians—the logic behind a money-losing proposition. N Engl J Med. 2011;364(19): 1790-1793. Confidence WITH EVERY STEP Give your patients confidence in their test results. Start with the ThinPrep® Pap test, the only pap test FDA approved as significantly more effective than the conventional pap smear for early detection. Add Dual Review with the ThinPrep Imaging System, proven to increase sensitivity and specificity over manually reviewed ThinPrep Pap test slides.1 Then, increase sensitivity to nearly 100% by recommending Cervista® HPV HR for women age 30 and older or patients with inconclusive pap results.2 Every step you take with ThinPrep and Cervista HPV leads to more accurate and reliable screening. Take the next step. Visit www.thinprep.com today. 1 The Imager clinical trial results showed a statistically significant increase in ASCUS+ sensitivity of 6.4% [95% CI: 2.6-10.0], a statistically significant increase in HSIL+ specificity of 0.2% [95% CI: 0.06-0.4], and a reduction in false negative fraction of 39% (based on ASCUS+ sensitivity). The unsatisfactory rate was not evaluated for statistical significance, but a decrease was observed. Ads-00196-001 Rev. 002 2 Consult package insert (http://www.cervistahpv.com/laboratory/cervistahpvhr/index.html) for full clinical details. Increasing calcium intake does not further reduce fracture risk Consuming more than 700 mg of calcium per day in later years does not further reduce the risk for fracture or osteoporosis and may, in fact, increase the risk for hip fracture, according to the ﬁndings of a large longitudinal and prospective cohort study from Sweden. Te study involved more than 61,000 women between 63 and 97 years of age participating in the Swedish Mammography Cohort, established in 1987. Of these, about 5,000 women participated in a subcohort. During 19 years of follow-up, almost 15,000 women, or just about one-quarter, experienced some type of ﬁrst fracture. Among those, 6% (3,871) experienced a ﬁrst hip fracture. Among the women in the subcohort, 20% met the criteria for osteoporosis. Te researchers found that the risk patterns associated with dietary calcium intake were Raising the cutoff level for a Hybrid capture 2 result New ﬁndings indicate that the cutoﬀ level for the Hybrid capture 2 test (Qiagen; Gaithersburg, Maryland) for primary screening for high-grade cervical intraepithelial neoplasia (CIN) can be increased to reduce the burden on women while still meeting international sensitivity recommendations. Te ﬁndings come from a systematic review of randomized controlled trials without metaanalysis, which was not possible because of the heterogeneity of the trials. Researchers found that the relative sensitivity for CIN grade III or higher at cutoﬀ levels of greater than or equal to 2, 4, 5, and 10 relative light units (rlu)/cutoﬀ (co) compared with a cutoﬀ level of greater than or equal to 1 rlu/co varied by trials. At their lowest, the values were 0.97, 0.92, and 0.91, respectively. Te investigators observed a similar pattern for CIN grade II or higher. Tey also found that speciﬁcity increased by at least 1%, 2%, and 3%, respectively, 14 CONTEMPORARYOBGYN.NET JULY 2011 NEWSLINE nonlinear. Tey calculated that the rate of a ﬁrst fracture of any type among women in the ﬁrst quintile of calcium intake (less than 751 mg per day) was 17.2 per 1,000 person-years at risk; for those in the second quintile (751 to 882 mg per day), the third quintile (882 to 996 mg per day), the fourth quintile (996 to 1,137 mg per day), and the ﬁfh quintile (greater than 1,137 mg per day), the rates were 14.7 (14.2 to 15.3), 14.0 (13.5 to 14.5), 14.1 (13.6 to 14.7), and 14.0 (13.5 to 14.5), respectively. Tose in the lowest quintile were at highest risk for a ﬁrst hip fracture, with an adjusted hazard ratio (HR) of 1.29 (1.17 to 1.43), but the group at next highest risk for hip fracture was the ﬁfh quintile, with an adjusted HR for hip fracture of 1.19 (1.06 to 1.32). A low vitamin D intake made the rate of fracture in the ﬁrst calcium quintile even more pronounced. Adjusted odds ratios for osteoporosis from the ﬁrst to the ﬁfh quintiles were as follows: 1.47 (1.09 to 2.00); 1.26 (0.99 to 1.60); 1.0 (reference); 0.92 (0.74 to 1.15); and 1.01 (0.81 to 1.27). Warensjö E, Byberg L, Melhus H, et al. Dietary calcium intake and risk of fracture and osteoporosis: prospective longitudinal cohort study. BMJ. 2011;342:d1473. so that women could avoid up to 24%, 39%, and 53% of false-positive Hybrid capture 2 test results (ie, results not associated with high-grade neoplasia). For example, a cutoﬀ greater than or equal to 10 rlu/co reduced the risk for a falsepositive result by about one-half among women 30 years of age and older. In younger women, the higher cutoﬀ reduced the risk for a false-positive result by about one-third. Recently published international recommendations for HPV screening in women 30 years of age and older require that new tests to detect HPV DNA demonstrate 90% or higher sensitivity for CIN grade II or higher compared with the sensitivity of the Hybrid capture 2 test using the cutoﬀ greater than or equal to 1 rlu/co. In addition, experts recommend that sensitivity of HPV screening for CIN grade III or higher be above 90%. Te researchers concluded that using a cutoﬀ for the Hybrid capture 2 between greater than or equal to 2 rlu/co and greater than or equal to 10 rlu/co meets these requirements. Rebolj M, Bonde J, Njor SH, Lynge E. Human papillomavirus testing in primary cervical screening and the cut-off level for hybrid capture 2 tests: systematic review. BMJ. 2011;342:d2757. CULTURA/I LOVE IMAGES/GETTY IMAGES Clinical Insights CLI N ICA L I NSIGHTS Women perceive USPSTF mammogram guidelines as unsafe A survey of 247 women 39 to 49 years of age reveals that 89% think that women in their forties should continue to receive yearly mammograms. Researchers from the University of Massachusetts Medical School in Worcester surveyed the women when they came to the hospital for annual well care visits. With regard to the United States Preventive Services Task Force (USPSTF) 2009 recommendations to raise the minimum age at which women receive regular mammographic screening from 40 to 50 years, 86% of the women surveyed believed the recommendations to be unsafe. In fact, even if their physician recommended they do so, 85% of the surveyed women reported that they would not wait until age 50 years to obtain a mammogram. Te BLEND IMAGES/LARRY WILLIAMS/GETTY IMAGES Is mesh better than colporrhaphy for pelvic organ prolapse? Compared with anterior colporrhaphy, a trocarguided transvaginal polypropylene mesh repair kit for prolapse of the anterior vaginal wall (cystocele) results in higher short-term success rates, but also higher rates of surgical complications and postoperative adverse events, according to the ﬁ ndings of a multicenter, parallel-group, randomized, controlled trial from Scandinavia. Researchers from Sweden, Finland, Norway, and Denmark randomly assigned 389 women from 53 clinics to cystocele repair with a mesh kit (the same type used routinely for hernias and incontinence) or to traditional colporrhaphy. At 1 year, using the Pelvic Organ Prolapse Quantiﬁcation system, almost twice as many women (60.8%) who were treated with the mesh repair kit were at the anatomical designation of stage 0 (no prolapse) NEWSLINE USPSTF guidelines also suggested that women between the ages of 50 and 74 years do not need a mammogram any more frequently than every 2 years. Te researchers also found that 88% of the women overestimated their lifetime risk for breast cancer. Tose women who received previous false-positive mammogram results and those with a friend diagnosed with breast cancer were even less likely to accept delaying screening until age 50 years. Te researchers had the women read a few articles on the subject and then complete the questionnaire. Tey found that consistent and highproﬁ le media campaigns had been eﬀective over the years in convincing women that early and regular mammograms lead to early detection, which, in turn, saves lives. Davidson ATS, Liao X, Magee BD. Attitudes of women in their forties toward the 2009 USPSTF mammogram guidelines: a randomized trial on the effects of media exposure. Am J Obstet Gynecol. April 15, 2011. Epub ahead of print. or 1 (position of the anterior vaginal wall more than 1 cm above the hymen) as those who underwent colporrhaphy (34.5%) (absolute diﬀerence, 26.3 percentage points; 95% conﬁdence interval [CI], 15.6 to 37.0). However, surgery lasted longer and rates of intraoperative hemorrhage were higher in the mesh repair group than in the colporrhaphy group (P<0.001 for both comparisons), as were rates of bladder perforation (3.5% vs 0.5%, respectively) and new stress urinary incontinence (12.3% vs 6.3%, respectively). In addition, 3.2% of the 186 women in the mesh group required surgical intervention to correct mesh exposure during follow-up. Investigators noted complications for as long as 1 year afer surgery with the mesh kit. Te authors of the study concluded that physicians, in collaboration with their patients, must weigh the risks and beneﬁts of each treatment option. Altman D, Väyrynen T, Engh ME, Axelsen S, Falconer C, for the Nordic Transvaginal Mesh Group. Anterior colporrhaphy versus transvaginal mesh for pelvic-organ prolapse. N Engl J Med. 2011;364(19):1826-1836. JULY 2011 CONTEMPORARY OB/GYN 15 BY DAWN COLLINS, JD R IS K M A N AG E M EN T I N O B S T E T R I C S A N D GY N ECO LO GY Retained sponge following hysterectomy: Who was negligent? A FLORIDA WOMAN underwent a hysterectomy performed by her gynecologist in 2007. Tree months later the patient returned with abdominal pain and was diagnosed with appendicitis. She underwent emergency surgery, during which a surgical sponge was discovered in the abdominal cavity. Te patient had developed an interabdominal infection that required a bowel resection. Te woman sued her gynecologist and the hospital, alleging that they were negligent in leaving the sponge behind during her hysterectomy. Te hospital settled prior to trial, but the physician maintained that the negligence was on the part of the surgical nurses in their sponge count. A defense verdict was returned for the physician. LEGAL PERSPECTIVE It is most likely that in this case the sponge and needle count was reported correctly, which would account for the hospital settling the case and allowing the physician to point to the nurses’ error. Despite counting procedures, errors still occur and some studies have shown that in 62% Malpractice fears hamper physicianto 88% of cases involving patient communication, according a retained foreign object to a recent study. Read more: (RFO) the sponge and contemporaryobgyn.net/suits needle count is erroneously reported as correct. Preventing RFOs requires a multidisciplinary systematic approach (See Stiller RJ, Tompson T, Ivy MJ. Preventing retained foreign objects in ob/gyn surgery. Contemporary OB/GYN. 2010;55[6]: 22-28). In malpractice cases involving an RFO, the negligence usually is assumed by the fact that an instrument or sponge was lef in the patient’s body. Damages and their MS COLLINS is an attorney specializing in medical malpractice in Long Beach, California. She welcomes feedback on this column via e-mail to dawncfree@gmail.com. 16 CONTEMPORARYOBGYN.NET JULY 2011 monetary value then become the issue. Tese can include any operation or procedure required to remove the RFO, an assessment of pain and suﬀering directly related to the RFO that have been experienced by the patient, and any long-term sequelae resulting from the alleged negligence. In this case, the physician maintained that the patient would have required surgery for the appendicitis anyway, and so she did not have an extra operation to support her claim for damages. Pulmonary embolism after cesarean delivery results in death IN 2005, A 29-YEAR-OLD ILLINOIS WOMAN, pregnant with twins, had a history of 2 prior cesarean deliveries. She was hospitalized for 6 days on bed rest because of preterm contractions. Te patient was discharged home and subsequently was seen several times at the hospital as an outpatient. Tree weeks later she was admitted to the hospital in labor. A cesarean delivery was performed later that day. As the delivery was completed, the patient suddenly became unresponsive and resuscitation attempts were unsuccessful. An autopsy revealed a massive saddle pulmonary embolus, which likely had come from a deep vein thrombus in the legs or pelvis. A lawsuit was ﬁled and her family testiﬁed that the woman had been told to remain on bed rest whenever possible at home and that she had done so. Tey alleged that when bed rest was recommended, the patient should have been started on deep vein thrombosis prophylaxis such as thromboembolic deterrent hosiery, sequential compression devices, and/or heparin. Te defense maintained that no restrictions had been placed on the patient’s activity at home, that she had not been placed on strict bed rest, and that the standard of care required deep vein thrombosis prophylaxis only for patients with a prior history of clots or thrombophilia. Tey argued that the patient had neither medical condition. Tey also argued that heparin would have Maximum Patient Comfort Lowest Complication Rate 1,2 Shown Actual Size Ultra-Slim 5.5 mm Probe 3 The Best Choice for In-Ofﬁce Endometrial Ablation Procedures • Exceptional patient outcomes...high patient satisfaction 4 • Short and efﬁcient total treatment time from pre-procedure to recovery • Sub-zero temperature provides a natural analgesic effect 5 • No intravenous sedation required To ﬁnd out how Her Option can beneﬁt your practice...and your patients, call 800.243.2974 or visit www.HerOption.com 1,2, 3, 4, 5 for reference details see http://www.coopersurgical.com/Documents/HerOptionBrochure.pdf 81788 Rev. 01/11 © 2011 CooperSurgical, Inc. LEGALLY SPEAKING increased the risk of bleeding and that mechanical prophylaxes such as thromboembolic deterrent hosiery and sequential compression devices were not eTective in preventing pulmonary embolism or death. A defense verdict was returned. Woman alleges postpartum hysterectomy was unnecessary A 30-YEAR-OLD ILLINOIS WOMAN presented at the hospital emergency department in 2004 with heavy vaginal bleeding 12 days afer giving birth to her third child. She was evaluated by an obstetrician and an ultrasound was performed. ﬀe scan found retained products of conception with pieces of placental tissue attached to the uterine wall, and a suction dilation and curettage was performed. ﬀe patient was given 2 medications to help her uterus to contract in an eTort to stop the bleeding. When the bleeding did not slow or stop the obstetrician called his senior partner for a second opinion. Both doctors then performed exploratory surgery to identify the source of the bleeding. ﬀey found that the bleeding was diT use throughout the uterus and that the patient already had lost about one-third to one-half of her total blood volume. ﬀey performed a total abdominal hysterectomy. ﬀe patient sued both obstetricians, alleging negligence in performing the hysterectomy. She argued that in addition to being unable to have more children, she suTered chronic pain syndrome as a result of the procedure. ﬀe physicians claimed that they had acted appropriately and had saved the woman’s life. A defense verdict was returned. Complications from ureter injury during surgery for pelvic prolapse A CALIFORNIA WOMAN, 38 years of age, was referred to a gynecologist in 2008 for severe problems with urinary stress incontinence and pelvic prolapse. Surgery was performed using mesh to repair the prolapse, and included a cystocele repair with bilateral sacrospinous ligament ﬁ xation and a prepubic transvaginal sling. Afer the operation the patient suTered pain and fever. A diagnostic laparoscopy performed the next day failed to ﬁnd a suspected bowel perforation; however, 18 CONTEMPORARYOBGYN.NET JULY 2011 an intravenous pyelogram revealed a lef ureteral injury. ﬀe patient was transferred to another hospital for stent placement. She developed a vesicovaginal ﬁstula that included mesh erosion to the bladder. In her lawsuit against the gynecologist, the patient claimed that the initial surgery was not indicated and that conservative treatment should have been tried ﬁrst. She also claimed that too many procedures were done at 1 time, which increased the risk of complications. She also alleged surgical error and mismanagement of her postoperative complications. ﬀe physician claimed that the surgery was indicated, that the patient had not been interested in conservative care, and that the complications she experienced were known risks of the procedure. A defense verdict was returned. Failure to diagnose postpartum breast infection alleged IN 2007, A MISSOURI WOMAN developed a swollen, tender area on her right breast almost 3 weeks afer giving birth. She informed her physician about her condition and told him that pus was oozing from the nipple. ﬀe physician diagnosed a clogged milk duct and prescribed an antibiotic for her. Her condition worsened over the next 2 weeks until milk ceased to ﬂow and her breast became red, painful, and warm. Her obstetrician prescribed a new antibiotic, and at her next oﬃce visit he told her to let the breast milk dry up. Within 24 hours of that visit, pus came through the skin at a point several centimeters above the nipple. ﬀe patient went to an emergency room and an abscess was diagnosed. She underwent surgery during which 100 cc of exudate was removed. ﬀe infection was caused by methicillin-resistant Staphylococcus aureus that was unaTected by the antibiotics prescribed. ﬀe patient’s lef breast also was infected; however, it was caught early enough to be drained with a needle. ﬀe patient sued her obstetrician, claiming that the infection should have been diagnosed earlier and that the infection could not have grown as quickly as the physician claimed it had. ﬀe physician argued that the infection had developed afer the patient’s last oﬃce visit and that staph infections are unusual in nursing mothers. He claimed that the patient had had a clogged milk duct when he saw her and that the infection developed closer to the time that her right nipple began oozing pus. A $200,000 verdict was returned against the obstetrician. JUST BECAUSE AN INCISION STARTS OUT SIMPLE DOESN’T MEAN IT ENDS UP THAT WAY PREVENA™ INCISION MANAGEMENT SYSTEM The first powered negative pressure product designed specifically for management of clean closed surgical incisions For more information, call KCI toll-free at 1.800.275.4528 or visit www.kci1.com Follow local institutional protocols for infection control and waste disposal procedures. Local protocols should be based on applicable local government environmental regulations. NOTE: Speciﬁc indications, contraindications, warnings, precautions and safety information exist for the PrevenaTM Incision Management system. Please consult a physician and product instructions for use prior to application. Rx only. ©2010 KCI Licensing, Inc. All Rights Reserved. All trademarks designated herein are proprietary to KCI Licensing, Inc., its afﬁliates and/or licensors. DSL#10-0506.COGÊUÊÉ£ä GRAND ROUNDS BSO: Solving the risk/benefit equation Choosing candidates, monitoring outcomes Prophylactic bilateral oophorectomy at the time of hysterectomy confers long-term health beneﬁts for many women. BY WILLIAM H PARKER, MD B Review the Society of Gynecologic Oncologists’ guidelines on prophylactic BSO in women at risk for ovarian cancer: contemporaryobgyn. net/BSO 20 ilateral oophorectomy at the time of hysterectomy for benign disease has been commonly recommended to women over the age of 40 or 45 years to prevent the development of ovarian cancer. In the United States, at least 300,000 women annually have bilateral oophorectomy at the time of hysterectomy: approximately 54% of all hysterectomy procedures.1 Concomitant bilateral oophorectomy is most ofen performed in women 50 to 54 years of age. In this group, 78% of hysterectomies include bilateral oophorectomy.1 However, prophylactic surgery should be performed only if there is evidence that it clearly beneﬁts the patient.2 Recent evidence suggests that there may be long-term health beneﬁts and longer survival for women who choose ovarian conservation at the time of hysterectomy for benign disease. In addition, oophorectomy improves quality of life and provides a survival benefit for other women.3 CONTEMPORARYOBGYN.NET JULY 2011 Ovarian cancer prevention in women at increased risk Although the lifetime risk of ovarian cancer is 1.4% overall among US women, the risk varies by subgroup. For example, white women at age 65 who have had 3 or more term pregnancies and at least 4 years of combined oral contraceptive (OC) use have a risk of 0.3%, whereas nulliparous women with the same OC use have a risk of 1.6%.4 Moreover, some women have mutations in the BRCA1 or BRCA2 gene, and such mutations may disrupt DNA repair mechanisms, predisposing these women to oncogenesis in the ovary and breast.5 It appears at present that no more than 10% of epithelial ovarian cancers are due to inherited mutations in ovarian cancer-related genes. 6,7 Nevertheless, the lifetime risk of ovarian cancer among women with these mutations is very high: for women with BRCA1 mutations the risk is 36% to 46%, and for BRCA2 mutations the risk is 10% to 27%.8 In addition, ILLUSTRATION BY CHRISTY KRAMES, MA, CMI women with the hereditary nonpolyposis colorectal cancer mutation have a 12% lifetime risk of ovarian cancer.9 For women with BRCA1 and BRCA2 mutations, annual screening for ovarian cancer using transvaginal ultrasound and the CA125 blood test has not proven efective for detecting disease early enough to inﬁuence survival, and is not recommended.10 ﬀe only intervention shown to be efective in reducing the incidence of ovarian cancer in women carrying the BRCA1 or BRCA2 gene mutation is bilateral salpingo-oophorectomy.11 As a result, authorities agree that women who have known genetic mutations that increase the risk of ovarian and breast cancers should strongly consider oophorectomy aﬂer completion of childbearing.12 About 2% of women have a family history consistent with an increased risk of ovarian or breast cancer. Recent studies suggest that a large number of low-penetrance genetic variants account for instances of women who have a strong family history but do not have BRCA1 or BRCA2 mutations.13 Genetic counseling from a trained healthcare provider can help these women make informed decisions about the advisability of oophorectomy. Removal of the fallopian tubes and ovaries in women with the BRCA1 or BRCA2 gene mutation reduces the risk of ovarian cancer by 80%.14 Further, a large retrospective study noted a decreased risk of breast cancer during follow-up after unilateral oophorectomy alone or bilateral oophorectomy performed with or without hysterectomy, particularly when these procedures were done before age 45 years (ratio of observed to expected cases ranging from 0.65 to 0.89).15 Both fallopian tubes also should be removed at surgery because recent evidence has shown that most BRCA-related ovarian cancers are actually of tubal origin, beginning in the epithelial cells of the T mbria of the fallopian tube.16 ﬀ is T nding also explains why ultrasound is not effective for cancer screening. Additionally, some women without a family or personal history that increases their risk of ovarian cancer may wish to have their ovaries removed because of concerns about the possibility of developing ovarian cancer. If one of these women wishes to proceed with oophorectomy aﬂer a full discussion of her specific risk for ovarian and breast cancers and the risks and beneTts of the surgery, I would certainly respect her wishes. Risks and side effects of oophorectomy Oophorectomy appears to be associated with long-term health risks. In premenopausal women, oophorectomy immediately reduces blood levels of ovarian estrogens and androgens. Even aﬂer menopause, the ovaries continue to produce significant amounts of testosterone and androstenedione, which undergo peripheral conversion to estrone by skin, muscle, and fat cells.17,18 Evidence indicates that endogenous estrogens are beneTcial to the cardiovascular system and for long-term health and neurologic function.19-22 ﬀis is a crucial consideration because although ovarian cancer causes JULY 2011 CONTEMPORARY OB/GYN 21 BILATERAL OOPHORECTOMY POWER POINTS Bilateral oophorectomy during hysterectomy is often recommended to prevent development of ovarian cancer. Prophylactic surgery should be recommended only if it would beneﬁt the patient. Women with BRCA1/2 or hereditary nonpolyposis colorectal cancer mutations are at increased risk for breast and ovarian cancers, and should consider prophylactic bilateral salpingooophorectomy. 22 approximately 15,000 deaths per year in the US, coronary heart disease (CHD) accounts for 327,000 deaths per year, 20 and dementia attributable to bilateral oophorectomy may affect between 100,000 and 200,000 US women.21 For example, a Danish cohort study found 7 times the risk of ischemic heart disease in women with a history of oophorectomy before age 40 years compared with women having oophorectomy afer age 45 years. ﬁe risk of heart disease increased with younger age at oophorectomy.22 With regard to neurologic function, a cohort study of premenopausal women undergoing unilateral or bilateral oophorectomy found that cognitive impairment or dementia occurred in 76 of 813 women (9.3%), representing nearly a 50% increase in risk.23 Dat a f rom t he Nu rses’ Hea lt h Study corroborate these findings. During 24 years of follow-up, oophorectomy was associated with increased risks of death from CHD (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.001.64) and death from all causes (HR, 1.12; 95% CI, 1.03-1.21). 20 Among women who had never used estrogen therapy, bilateral oophorectomy before 50 years of age was associated with increased risks of all-cause mortality, CHD, and stroke. Given that the life expectancy after surgery is 35 years, 1 additional death would be expected for every 9 oophorectomies performed before age 50. After oophorectomy, women had a markedly reduced risk of ovarian cancer; however, they had higher risks of lung cancer (HR, 1.31; 95% CI, 1.02-1.68) and total cancer mortality (HR, 1.17; 95% CI, 1.04-1.32). Oophorectomy was not associated with increased survival in any analysis or age group. In addition to its eﬀects on CHD risk and cognitive impairment or dementia, bilateral oophorectomy before the onset of menopause has been shown to increase the risks of Parkinson disease and anxiety or depression.23-25 Younger age at oophorectomy increased the risks for these neurologic conditions. Although a recent analysis of the Women’s Health Initiative (WHI) found that bilateral oophorectomy might not increase CONTEMPORARYOBGYN.NET JULY 2011 the risks of cardiovascular disease, cancer, or overall mortality when compared with ovarian conservation, this study had a short follow-up (mean, 7.6 years).26 Because 20% of myocardial infarctions occur before age 65 and women were an average age of 63 years when the WHI enrollment began, some selection bias cannot be ruled out. In addition, the premenopausal operations were self-reported, which means that the data may be aﬀected by recall bias. A review of prophylactic oophorectomy by the Society of Gynecologic Oncologists Clinical Practice Committee suggested that ovarian conservation before menopause may be especially important in patients with a personal or strong family history of cardiovascular or neurologic disease.27 ﬁe decision to perform concurrent bilateral salpingooophorectomy in women at average risk of ovarian cancer therefore should include a consideration of individual risk factors, such as family history of cardiovascular and neurologic disease, OC use, parity, and other epidemiologic factors. 28 Careful preoperative counseling is required, and the decision should be individualized. Estrogens and androgens inhibit bone resorption, and androgens stimulate bone formation.29 Both premenopausal and postmenopausal women who undergo bilateral oophorectomy have an increased risk of osteoporosis because of the reduction in hormone levels. Postmenopausal women who underwent oophorectomy at a median age of 62 years had 54% more osteoporotic fractures than those with intact ovaries.30 However, 2 other studies found no association of oophorectomy with bone loss or fracture risk.31,32 About 90% of premenopausal women have vasomotor symptoms after oophorectomy, 33 and many women also experience mood changes, a decline in feelings of well- being, decreased sexual desire, sleep disturbances, and headaches. 34-36 Over time, vaginal dryness, painful intercourse, bladder dysfunction, and symptoms of depression may occur. 36-38 Although estrogen therapy may reduce some of the increased risks and symptoms that occur afer oophorectomy, continuation rates of BUILDING CALCIUM COMPLIANCE INTRODUCING CITRACAL Slow Release 1200 ® The only* calcium supplement taken just once daily • Slo-Cal™ Technology releases calcium continuously for efﬁcient absorption • 24-hour urine excretion levels were signiﬁcantly lower than with Os-Cal® and Caltrate® 1 • 1200 mg of calcium plus 1000 IU of Vitamin D3 in 2 tablets (one dose) RECOMMEND CITRACAL Slow Release *Among leading brands. Os-Cal is a registered trademark of GlaxoSmithKline. Caltrate is a registered trademark of Pﬁzer, Inc. Reference: 1. Data on ﬁle. CITRACAL study. Bayer HealthCare LLC. © 2011 Bayer HealthCare LLC January 2011 42383-6333 BUILT FOR COMPLIANCE BILATERAL OOPHORECTOMY POWER POINTS Risks associated with oophorectomy, particularly in younger women, include heart disease, cognitive impairment/dementia, Parkinson disease, and depression. In women at average risk for ovarian cancer, strategies other than surgery may be advised. In women with breast cancer, oophorectomy combined with tamoxifen therapy has prolonged 10-year disease-free survival rates more effectively than tamoxifen therapy alone. 24 estrogen therapy are low and new hormone prescriptions have decreased significantly over the past decade.39 Likewise, continuation rates for bisphosphonates or statins as specific therapy for osteoporosis or heart disease are less than 25% after 1 year.40,41 Critics suggest that medical therapy can ameliorate all the medical conditions caused by oophorectomy, but this argument is not valid because of the poor continuation rates of these medications. Therefore, medical treatment for conditions related to estrogen defciency aﬁer oophorectomy is not likely to be eﬀective for most women. Ovarian cancer prevention for women at average risk ﬂeoretically, there may be an age at which the benefits of oophorectomy to prevent ovarian cancer outweigh the possibility of increased risks of CHD, neurologic conditions, and overall mortality in low-risk women. ﬂe incidence of ovarian cancer increases with age, peaking at approximately 75 years. It is likely that with advancing age, the inTuence of ovarian hormones decreases compared with that of other known risk factors for heart disease and other causes of mortality. A computer modeling study examined risk data among women with and without oophorectomy and found that ovarian conservation until at least age 65 years improved long-term survival for women who had an average risk of ovarian cancer.42 However, no study has determined the age at which oophorectomy should be recommended. Endogenous bioavailable testosterone and estrogen in postmenopausal women are partly protective against the loss of muscle strength that predisposes these women to falls and against the continuing loss of bone mineral density that increases the risk of fractures.43 ﬂerefore, even in older women, these ovarian hormones may have beneft. Other strategies may be taken to decrease the risk of ovarian cancer, including the use of OC pills or tubal ligation. Taking OCs for 5 or more years decreases the risk of ovarian cancer by 50%,28 and tubal ligation decreases the risk by 34%.44 Hysterectomy alone decreases the risk of ovarian cancer by 33%.45 CONTEMPORARYOBGYN.NET JULY 2011 Oophorectomy and breast cancer A case-control study showed that oophorectomy reduced the risk of breast cancer by 56% for BRCA1 and 46% for BRCA2 carriers.46 Risk reduction was even greater for women younger than 40 years at surgery, and the protective eﬀect persisted 15 years after surgery. A study of a general Swedish population showed a 50% reduction in the risk of breast cancer among women who had bilateral oophorectomy before age 50 years, and this eﬀect was evident within 10 years of the surgery.47 Oophorectomy may be recommended as treatment for some women with breast cancer. Although tamoxifen and aromatase inhibitors are typically used to prevent recurrences of breast cancer in postmenopausal women with estrogen-receptor‒positive, early stage tumors, some investigators recommend oophorectomy combined with tamoxifen therapy. ﬂis combination treatment was associated with higher 10-year disease-free survival than was reported for women treated with tamoxifen alone.48 In addition, oophorectomy has been used as treatment for premenopausal women with metastatic breast cancer, achieving response rates of 14% to 70%, depending on the study.49 Patients with breast cancer in clinical remission who are undergoing a hysterectomy for benign disease may consider concurrent oophorectomy because it has been associated with a reduction in the risk of relapse.50 Oophorectomy and endometriosis Among women with severe, symptomatic endometriosis unresponsive to conservative management, bilateral oophorectomy concurrent with hysterectomy decreased the risks of recurrent or persistent symptoms and the need for reoperation. 51 One study of women with symptomatic endometriosis compared outcomes between women who had a hysterectomy with ovarian conser vation and women who had a hysterectomy with concurrent bilateral o ophore c tomy. 52 O f t he 29 women with ovarian conservation, 18 (62%) had recurrent pain and 9 (31%) required reopera- BILATERAL OOPHORECTOMY tion. Of the 109 women who had both ovaries removed, 11 (10%) had recurrent pain and 4 (4%) required reoperation. Women who underwent hysterectomy with ovarian conservation had 6 times the risk of developing recurrent pain and 8 times the risk of reoperation compared with women who had concurrent bilateral oophorectomy. Another study of conﬁrmed endometriosis found that of the 47 women who had a hysterectomy with ovarian conservation, 9 (19%) required further surgery.53 Te 2-, 5-, and 7-year reoperation rates were 4%, 13%, and 23%, respectively. Of the 50 women who had a hysterectomy with bilateral oophorectomy, only 4 (8%) required reoperation, with reoperation rates of 4% at 2 years, 8% at 5 years, and 8% at 7 years. Preservation of both ovaries doubled the risk of reoperation regardless of the patient’s age. Te authors concluded that local excision of endometriosis is associated with good short-term outcomes but has a high reoperation rate, whereas hysterectomy with bilateral salpingo-oophorectomy has a low reoperation rate. In contrast, an analysis of women younger than 40 years with advanced endometriosis found that the time to repeat surgery was the same whether the ovaries were removed or conserved. Given the problems associated with early menopause, the authors recommended that for women younger than 40 years of age, hysterectomy with ovarian conservation should be considered.53 Avoiding future adnexal surgery Te percentage of women who require reoperation after hysterectomy with ovarian conservation is low, with residual ovary syndrome occurring at a rate of approximately 2.8%. 54 Asymptomatic cystic ovarian tumors are relatively prevalent (6.6%) in postmenopausal women. 55 These cysts do not undergo transformation to cancer, however, and in most cases do not need to be removed. Another study reported that only 0.75% of women developed ovarian cancer afer hysterectomy and ovarian conservation performed by the vaginal or abdominal route.56 Performing oophorectomy to avoid future surgery appears unfounded. Summary Medical decisions involve a balance of beneﬁts and risks for each individual patient. Prophylactic surgery should be performed only if the weight of the evidence establishes that it clearly beneﬁts the patient. Undoubtedly, bilateral salpingo-oophorectomy is advisable for women who have a high risk of ovarian and breast cancer because of gene mutations. In addition, women older than 40 years with severe endometriosis unresponsive to conservative treatment may beneﬁt from oophorectomy. The decision about oophorectomy for other women is problematic, and more research will be needed to answer the remaining clinical questions. Unfortunately, the entire body of evidence that examines the risks and benefits of bilateral salpingo-oophorectomy is derived from observational studies, which have significant inherent limitations. At a minimum, gynecologists should provide detailed informed consent covering the risks and benefits of both oophorectomy and ovarian conservation. POWER POINTS In women with endometriosis, oophorectomy during hysterectomy has reduced system recurrence and need for repeat surgery. DR PARKER is on the adjunct faculty of the John Wayne Cancer Institute at St John’s Health Center and in private practice in Santa Monica, California. He reports no real or apparent conflicts of interest with respect to the content of this article. REFERENCES 1. Whiteman MK, Hillis SD, Jamieson DJ, et al. Inpatient hysterectomy surveillance in the United States, 2000-2004. Am J Obstet Gynecol. 2008;198(1):34.e1-34.e7. 2. Asante A, Whiteman MK, Kulkarni A, Cox S, Marchbanks PA, Jamieson DJ. Elective oophorectomy in the United States: trends and in-hospital complications, 1998-2006. Obstet Gynecol. 2010;116(5):1088-1095. 3. Hickey M, Ambekar M, Hammond I. Should the ovaries be removed or retained at the time of hysterectomy for benign disease? Hum Reprod Update. 2010;16(2):131-141. 4. Hartge P, Whittemore AS, Itnyre J, McGowan L, Cramer D; the Collaborative Ovarian Cancer Group. Rates and risks of ovarian cancer in subgroups of white women in the United States. Obstet Gynecol. 1994;84(5):760-764. 5. Tutt A, Ashworth A. The relationship between the roles of BRCA genes in DNA repair and cancer predisposition. Trends Mol Med. 2002;8(12):571-576. 6. Stratton JF, Gayther SA, Russell P, et al. Contribution of BRCA1 mutations to ovarian cancer. N Engl J Med. 1997;336(16):1125-1130. JULY 2011 CONTEMPORARY OB/GYN 25 BILATERAL OOPHORECTOMY 7. Tinelli A, Malvasi A, Leo G, et al. Hereditary ovarian cancers: from BRCA mutations to clinical management. A modern appraisal. Cancer Metastasis Rev. 2010;29(2): 339-350. 8. Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst. 2009;101(2):80-87. 9. Schmeler KM, Lu KH. Gynecologic cancers associated with Lynch syndrome/HNPCC. Clin Transl Oncol. 2008;10(6):313-317. 10. Evans DG, Gaarenstroom KN, Stirling D, et al. Screening for familial ovarian cancer: poor survival of BRCA1/2 related cancers. J Med Genet. 2009;46(9):593-597. 11. Kauff ND, Domchek SM, Friebel TM, et al. Riskreducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: a multicenter, prospective study. J Clin Oncol. 2008;26(8):1331-1337. 12. Armstrong K, Schwartz JS, Randall T, Rubin SC, Weber B. Hormone replacement therapy and life expectancy after prophylactic oophorectomy in women with BRCA1/2 mutations: a decision analysis. J Clin Oncol. 2004;22(6):1045-1054. 13. Mackay J, Szecsei CM. Genetic counseling for hereditary predisposition to ovarian and breast cancer. Ann Oncol. 2010;21(Suppl 7):vii334-vii338. 14. Finch A, Beiner M, Lubinski J, et al; Hereditary Ovarian Cancer Clinical Study Group. Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 mutation. JAMA. 2006;296(2):185-192. 24. Rocca WA, Bower JH, Maraganore DM, et al. Increased risk of parkinsonism in women who underwent oophorectomy before menopause. Neurology. 2008;70(3):200-209. 25. Rocca WA, Grossardt BR, Geda YE, et al. Long-term risk of depressive and anxiety symptoms after early bilateral oophorectomy. Menopause. 2008;15(6):1050-1059. 26. Jacoby VL, Grady D, Wactawski-Wende J, et al. Oophorectomy vs ovarian conservation with hysterectomy: cardiovascular disease, hip fracture, and cancer in the Women’s Health Initiative Observational Study. Arch Intern Med. 2011;171(8):760-768. 27. Berek JS, Chalas E, Edelson M, et al; Society of Gynecologic Oncologists Clinical Practice Committee. Prophylactic and risk-reducing bilateral salpingooophorectomy: recommendations based on risk of ovarian cancer. Obstet Gynecol. 2010;116(3):733-743. 28. Riman T, Nilsson S, Persson IR. Review of epidemiological evidence for reproductive and hormonal factors in relation to the risk of epithelial ovarian malignancies. Acta Obstet Gynecol Scand. 2004;83(9): 783-795. 29. Raisz LG, Wiita B, Artis A, et al. Comparison of the effects of estrogen alone and estrogen plus androgen on biochemical markers of bone formation and resorption in postmenopausal women. J Clin Endocrinol Metab. 1996;81(1):37-43. 30. Melton LJ 3rd, Khosla S, Malkasian GD, Achenbach SJ, Oberg AL, Riggs BL. Fracture risk after bilateral oophorectomy in elderly women. J Bone Miner Res. 2003;18(5):900-905. 15. Kreiger N, Sloan M, Cotterchio M, Kirsh V. The risk of breast cancer following reproductive surgery. Eur J Cancer. 1999;35(1):97-101. 31. Kritz-Silverstein D, von Mühlen DG, Barrett-Connor E. Hysterectomy and oophorectomy are unrelated to bone loss in older women. Maturitas. 2004;47(1):61-69. 16. Callahan MJ, Crum CP, Medeiros F, et al. Primary fallopian tube malignancies in BRCA-positive women undergoing surgery for ovarian cancer risk reduction. J Clin Oncol. 2007;25(25):3985-3990. 32. Antoniucci DM, Sellmeyer DE, Cauley JA, et al; Study of Osteoporotic Fractures Research Group. Postmenopausal bilateral oophorectomy is not associated with increased fracture risk in older women. J Bone Miner Res. 2005;20(5):741-747. 17. Judd HL, Judd GE, Lucas WE, Yen SS. Endocrine function of the postmenopausal ovary: concentration of androgens and estrogens in ovarian and peripheral vein blood. J Clin Endocrinol Metab. 1974;39(6):1020-1024. 18. Fogle RH, Stanczyk FZ, Zhang X, Paulson RJ. Ovarian androgen production in postmenopausal women. J Clin Endocrinol Metab. 2007;92(8):3040-3043. 19. Colditz GA, Willett WC, Stampfer MJ, Rosner B, Speizer FE, Hennekens CH. Menopause and the risk of coronary heart disease in women. N Engl J Med. 1987;316(18): 1105-1110. 20. Parker WH, Broder MS, Chang E, et al. Ovarian conservation at the time of hysterectomy and long-term health outcomes in the Nurses’ Health Study. Obstet Gynecol. 2009;113(5):1027-1037. 21. Bennett DA. Editorial comment on ‘Prevalence of dementia in the United States: the Aging, Demographics, and Memory Study’ by Plassman et al. Neuroepidemiology. 2007;29(1-2):133-135. 22. Løkkegaard E, Jovanovic Z, Heitmann BL, Keiding N, Ottesen B, Pedersen AT. The association between early menopause and risk of ischaemic heart disease: influence of hormone therapy. Maturitas. 2006;53(2):226-233. 23. Rocca WA, Bower JH, Maraganore DM, et al. Increased risk of cognitive impairment or dementia in women who 26 underwent oophorectomy before menopause. Neurology. 2007;69(11):1074-1083. CONTEMPORARYOBGYN.NET JULY 2011 33. Hansen KA. Female reproductive biology. In: O’Leary JP, Tabuenca A, Capote LR (eds). The Physiologic Basis of Surgery, 4th ed. Philadelphia, Pennsylvania: Lippincott Williams & Wilkins; 2007:314-315. 34. Nathorst-Böös J, von Schoultz B, Carlström K. Elective ovarian removal and estrogen replacement therapy--effects on sexual life, psychological well-being and androgen status. J Psychosom Obstet Gynaecol. 1993;14(4):283-293. 35. Elit L, Esplen MJ, Butler K, Narod S. Quality of life and psychosexual adjustment after prophylactic oophorectomy for a family history of ovarian cancer. Fam Cancer. 2001; 1(3-4):149-156. 36. Taylor M. Psychological consequences of surgical menopause. J Reprod Med. 2001;46(3 Suppl):317-324. 37. Bachmann GA, Nevadunsky NS. Diagnosis and treatment of atrophic vaginitis. Am Fam Physician. 2000;61(10):3090-3096. 38. Shifren JL, Avis NE. Surgical menopause: effects on psychological well-being and sexuality. Menopause. 2007;14(3 Pt 2):586-591. 39. Wegienka G, Havstad S, Kelsey JL. Menopausal hormone therapy in a health maintenance organization before and after Women’s Health Initiative hormone trials termination. J Womens Health (Larchmt). 2006;15(4):369-378. BILATERAL OOPHORECTOMY 40. McCombs JS, Thiebaud P, McLaughlin-Miley C, Shi J. Compliance with drug therapies for the treatment and prevention of osteoporosis. Maturitas. 2004;48(3):271-287. adjuvant oophorectomy and tamoxifen in operable breast cancer in premenopausal women. J Clin Oncol. 2008;26(2):253-257. 41. Huser MA, Evans TS, Berger V. Medication adherence trends with statins. Adv Ther. 2005;22(2):163-171. 49. Prowell TM, Davidson NE. What is the role of ovarian ablation in the management of primary and metastatic breast cancer today? Oncologist. 2004;9(5):507-517. 42. Parker WH, Broder MS, Liu Z, Shoupe D, Farquhar C, Berek JS. Ovarian conservation at the time of hysterectomy for benign disease. Obstet Gynecol. 2005;106(2):219-226. 43. van Geel TA, Geusens PP, Winkens B, Sels JP, Dinant GJ. Measures of bioavailable serum testosterone and estradiol and their relationships with muscle mass, muscle strength and bone mineral density in postmenopausal women: a cross-sectional study. Eur J Endocrinol. 2009;160(4):681-687. 44. Cibula D, Widschwendter M, Májek O, Dusek L. Tubal ligation and the risk of ovarian cancer: review and metaanalysis. Hum Reprod Update. 2011;17(1):55-67. 45. Hankinson SE, Hunter DJ, Colditz GA, et al. Tubal ligation, hysterectomy, and risk of ovarian cancer. A prospective study. JAMA. 1993;270(23):2813-2818. 46. Eisen A, Lubinski J, Klijn J, et al. Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case-control study. J Clin Oncol. 2005;23(30):7491-7496. 47. Schairer C, Persson I, Falkeborn M, Naessen T, Troisi R, Brinton LA. Breast cancer risk associated with gynecologic surgery and indications for such surgery. Int J Cancer. 1997;70(2):150-154. 48. Love RR, Van Dinh N, Quy TT, et al. Survival after 50. Kelsey JL, Bernstein L. Epidemiology and prevention of breast cancer. Annu Rev Public Health. 1996;17:47-67. 51. Vercellini P, Barbara G, Abbiati A, Somigliana E, Viganò P, Fedele L. Repetitive surgery for recurrent symptomatic endometriosis: what to do? Eur J Obstet Gynecol Reprod Biol. 2009;146(1):15-21. 52. Namnoum AB, Hickman TN, Goodman SB, Gehlbach DL, Rock JA. Incidence of symptom recurrence after hysterectomy for endometriosis. Fertil Steril. 1995;64(5):898-902. 53. Shakiba K, Bena JF, McGill KM, Minger J, Falcone T. Surgical treatment of endometriosis: a 7-year follow-up on the requirement for further surgery. Obstet Gynecol. 2008;111(6):1285-1292. 54. Dekel A, Efrat Z, Orvieto R, et al. The residual ovary syndrome: a 20-year experience. Eur J Obstet Gynecol Reprod Biol. 1996;68(1-2):159-164. 55. Bailey CL, Ueland FR, Land GL, et al. The malignant potential of small cystic ovarian tumors in women over 50 years of age. Gynecol Oncol. 1998;69(1):3-7. 56. Naylor AC. Hysterectomy—analysis of 2901 personally performed procedures. S Afr Med J. 1984;65(7):242-245. The 1st & Only FDA Cleared Blood Test for Pre-Surgical Evaluation of Ovarian Masses A sensitive test for a sensitive subject. t OVA1® is the most clinically sensitive FDA cleared* blood test to evaluate an ovarian mass for malignancy before surgery. t OVA1 improved overall Sensitivity (95.7%) and NPV (94.6%) when combined with a physician’s Clinical Impression. (Overall data included patients [n=516] evaluated by either gynecologic oncologists or non-gynecologic oncologists.)1 t OVA1 is available nationwide exclusively through Quest Diagnostics. ova-1.com *FDA clearance does not denote ofﬁcial approval. 1OVA1 product insert. OVA1® is a qualitative serum test that combines the results of ﬁve immunoassays into a single numerical result. It is indicated for women who meet the following criteria: over age 18, ovarian adnexal mass present for which surgery is planned, and not yet referred to an oncologist. OVA1® is an aid to further assess the likelihood that malignancy is present when the physician’s independent clinical and radiological evaluation does not indicate malignancy. The test is not intended as a screening or stand-alone diagnostic assay. Vermillion and OVA1 are registered trademarks of Vermillion, Inc. BY ALLAN J JACOBS, MD, JD P R ACT I C A L A DV I CE F R O M CO M M U N I T Y P H YS I CI A NS Is “progress” good for your practice? S ince World War II, evidence-based medicine has rapidly replaced custom and lore. Proliferation of imaging and laboratory studies has improved diagnostic accuracy. Drugs and other treatments have vastly improved our ability to cure and alleviate disease. For example, survival rates for common kinds of cancer improved from 27% to 550% between the 1950s and the 1990s.1 But interestingly, as physicians’ effectiveness has increased, their satisfaction with their profession has diminished 2: A recent In 1973, less than physician 15% of several thousand survey shows practicing physicians many are reported any doubts that changing practice they had made the correct patterns. career choice. In contrast, Read more surveys administered at contemporaryobgyn.net/ within the past 10 years practice have shown that 30% to 40% of practicing physicians would not choose to enter the medical profession if they were deciding on a career again, and an even higher percentage would not encourage their children to pursue a medical career. In a telephone survey of 2,000 physicians that was conducted in 1995, 40% of the doctors said they CCLINICIAN TO CLINICIAN offers the hard-won w wisdom and expertise of physicians “in the trenches.” W looking for unusual case reports, anecdotes We’re about innovative treatments, and practical solutions for professional problems from community physicians. Send your submission of 750 words or less to Patricia M. Fernberg, Editor, by e-mail (pfernberg@advanstar.com). All submissions are subject to peer review by the Contemporary OB/GYN Editorial Advisory Board. Nevertheless, the concepts discussed may be anecdotal in nature. WE WANT TO HEAR FROM YOU 28 CONTEMPORARYOBGYN.NET JULY 2011 would not recommend the profession of medicine to a qualified college student. In a national survey in 1981, 48% of 1,426 oﬃcebased doctors said they would not recommend the practice of medicine as highly as they would have 10 years earlier. In a follow-up survey in 2001, 58% of 2,608 physicians said that their enthusiasm for medicine had declined in the previous 5 years, and 87% said that the overall morale of physicians had declined during that time. Massachusetts physicians who were asked in 2001 to recall their thoughts about medical practice 5 years earlier reported more current dissatisfaction with virtually all aspects of practice, including income, workload, and time consumed by administrative tasks. Among California physicians questioned in 1991 and again in 1996, the percentage who said they were less than fully satisﬁed with the practice of medicine rose from 53% to 63%. (Internal references omitted.) Te ultimate cause of physician dissatisfaction is the very phenomenon that has led to the success of medicine. Te change of medicine from a craf to an applied science has prompted changes in the nature of the work and the relationships of physicians with all relevant elements of society. T is, in turn, has spurred a decline in income, an increase in managed care, 3 and a rise in malpractice suits. Objective knowledge leads to best practices, which, in turn, leads to well-deﬁ ned standards. Physicians who comply with standards will do things in the same way and will have similar capabilities. T is makes them roughly interchangeable. T is is called industrialization. Industrialization allows organizations and payors to standardize medical roles and enforce standard rules, including practice modes and compensation. T is is called bureaucratization. Tese 2 phenomena leave physicians with little PHOTODISC/CHRISTINE BALDERAS/GETTY IMAGES Although science has produced new and improved procedures and pharmaceuticals that allow us to better treat patients, the byproducts of industrialization and bureaucratization diminish our status, job satisfaction, and income. Is there a happy medium? CLINICIAN TO CLINICIAN The change of medicine from a craft to an applied science has prompted changes in the nature of the work and the relationships of physicians with all relevant elements of society. leverage vis-à-vis payors, patients, government, and hospitals, which in turn decreases extrinsic satisfaction with the ﬃeld. ﬁe practice of medicine now also provides less intrinsic satisfaction. Standardization of practice makes medicine less creative. Furthermore, success is expected, and poor clinical results represent failure. Physicians are not heroes when successful, but are blamed for lack of success. Most feel the pressured by insurance companies to herd patients in and out of the door, push forms, and punch time clocks. Industrialization A visit to a physician used to cost about $10 in the 1950s, but some physicians charged more than $1,000 for the service. Today no physician’s service commands 100 times that of another’s. Professionals in other ﬃelds with unusual skills command vast amounts of money and respect. For every Andre Agassi or Meryl Streep, there are millions of weekend tennis players and amateur actors who are unable to make a living from their respective craTs. Partly for this reason, people with prized skills become known as artists. Artisans also vary in skill and in compensation, although not as much as artists. Industrial workers, on the other hand, have jobs with standardized outcomes that generally cannot be exceeded. ﬁey are supposed to perform a task correctly almost all of the time. ﬁis is possible because management has standardized and simpliﬃed the work. Finally, other jobs, such as that of a bank teller, are easy enough that a person provided minimal training will rarely make mistakes. When products and services arise from tasks and skills rather than from art and craT, a greater quantity of work output becomes possible, the products become less expensive, and the quality of the product becomes more consistent. For example, as the production of goods, such as guns and cloth, became industrialized in the early 19th century, prices fell and quality improved. Because there are more consumers of any product than there are producers, society welcomes industrialization. ﬁe down side is that industrialization decreases a worker’s intrinsic and extrinsic satisfaction with his or her work. When work quality varies, workers enjoy a greater degree of independence because clients and employers seek workers with unique or uncommon skills to accommodate their individual preferences. Furthermore, remuneration decreases as work becomes more reproducible. Similarly, the diference in value between excellent and average work decreases as work becomes standardized. ﬁe best athletes and actors earn many times more money than average ones, while the best and the worst clerks earn relatively the same. Any diferences in salary are not based on ability or performance but on factors unrelated to the job itself, such as seniority or location. Intrinsic satisfaction with work also declines with industrialization. Reproducibility of work minimizes judgment and creativity and increases boredom. It becomes easy to err and hard to excel. Industrial workers cannot do more than to perform a task correctly, but they can fail to do this. One either installs the widget correctly or errs. Clearly, avoiding failure provides less satisfaction than does striving for excellence. Industrialization decreases a worker’s intrinsic and extrinsic satisfaction with his or her work. The industrialization of medicine Physicians’ work is becoming industrialized. Prevention, diagnosis, and treatment of disease all have become more precise and standardized, and much more of medicine is governed by rules, guidelines, and procedures. At one time, physicians difered greatly in their abilities to take histories, perform examinations, and make clinical decisions. Surgeons varied in their ability to operate safely on patients. In a teaching JULY 2011 CONTEMPORARY OB/GYN 29 CLINICIAN TO CLINICIAN setting, citation of the practices of respected local clinicians was as acceptable as citation of literature. For at least the last 50 years, however, tests and treatments have become objectiﬁed and simpliﬁed. In the 1970s, for example, obstetricians estimated date of delivery (EDD) using the history and physical examination, which frequently conﬂ icted. Tey then had to use judgment to decide which factors to accept to establish EDD. Now early ultrasound accurately ﬁ xes the EDD. Similarly, obstetricians monitored for fetal distress during labor with intermittent auscultation. A good or lucky physician might perceive subtle slowing of the fetal heart rate. Now we need only view monitor strips to determine the fetus’s well-being. Where once the management of obstetric complications required experience and superior judgment, now nationally accepted standards govern treatment of such problems as hypertension and streptococcal infection. Obstetricians now consult perinatologists about problems to which guidelines do not readily apply. One not-so-fringe beneﬁt is that preventable causes of fetal mortality decreased by 65% between 1965 to 1990. 5 Te practice of gynecology also has undergone division of labor, standardization, and simpliﬁcation. Treatment of infertility and cancer now largely is handled by certiﬁed subspecialists. Generalists’ surgery has become simpler. For example, sterilization now is accomplished via hysteroscopic tubal occlusion instead of by vaginal hysterectomy or vaginal tubal ligation. New operative techniques, such as stapling and electrosurgery, have made old operations easier and safer. Guidelines for standard of care have proliferated. By 2010, the American College of Obstetricians and Gynecologists (ACOG) had adopted at least 67 clinical Committee Opinions or Practice Recommendations. Individual institutions have adopted many others. Other medical ﬁelds reveal comparable ﬁ ndings. Coronary bypass requires delicate, rapid, and It is extremely difﬁcult for physicians to obtain privileges for new procedures. accurate anastomosis of blood vessels. If diﬀerences in physicians’ skill inﬂuenced clinical results, they surely would for this procedure. Between 2006 and 2008, however, 122 physicians in New York performed at least 50 coronary bypass procedures. Only 7 of these surgeons had mortality rates statistically better or worse than the overall statewide rate of 1.81%. 5 At a signiﬁcance level of P<0.05, one would expect that 6 surgeons would be outliers if no one actually was better or worse than another. Te results indicate that almost any heart surgeon can perform coronary bypass as safely as any other, making heart surgeons virtually interchangeable to employers and payors. Researchers have found similar results among other kinds of surgeons.6,7 Preventive care and treatment of relatively minor common conditions are highly subject to standardization. For example, hospitals report achieving greater than 90% compliance with Surgical Care Improvement Project (SCIP) guidelines.8 Te use of audits9 and computerized records10,11 has enhanced enforcement of these guidelines. Compliance decreases surgical infection rates, but guidelines restrict physicians’ judgment. Physicians can err, but they cannot exceed the standard. Bureaucratization In the 1960s, a group of gynecologists in the United States integrated intestinal and urinary surgery and the administration of chemotherapy into their treatment of patients with cancer. Tey thus created the subspecialty of gynecologic oncology, improving the cure rate and safety for women with gynecologic cancer. No hospital now would now allow physicians to expand the scope of their practice the way these pioneers did. Hospitals deﬁne privileges precisely and award them to strictly deﬁned categories of physicians. It is extremely diﬃcult for physicians to obtain privileges for new procedures. Weber12 described bureaucratization as work governed by well-deﬁ ned roles, with rules governing those roles. Rules dictate how workers must perform, how their work is monitored, and how they are compensated. In medicine, such rules are provided by licensure, certiﬁcation, and credentialing, and by hospital and government laws, rules, and regulations. Increasingly, medical care is managed and dictated by algorithms produced by insurance companies and administered by clerks without healthcare training. continued on page 34 30 CONTEMPORARYOBGYN.NET JULY 2011 Christian Pettker, MD, lead author of a major patient safety study, performs an ultrasound on a patient. Yale-New Haven Hospital doctors and nurses conducted a four-year patient safety study that led to a 40 percent decrease in the hospital’s obstetrical adverse events. Their interventions included team training for hospital staff, standardizing interpretation of fetal monitoring, improved communication between staff and creating the role of patient safety nurse. While interventions of this sort involve fundamental culture change, commitment and persistence, Breaking new ground in the advancement of patient safety the improved outcomes proved that the hard work paid off. In addition to positive results that continue to this day, the program’s pioneering work recently led to an Award of Research Excellence from the Society for Maternal-Fetal Medicine. Our efforts are not only changing how we care for patients at Yale-New Haven, but they are leading the way in the obstetrical patient safety movement across the country. Yale-New Haven Hospital is the primary teaching hospital of Yale School of Medicine. Gynecology services at Yale-New Haven were ranked 15th by U.S.News & World Report in 2010-11. www.ynhh.org Introducing With DHA plus iodine and biotin! Nothing is too good for her little prince > 150 mcg of iodine to compensate for the general reduction in iodine status in the USA1* > Severe iodine deﬁciency during pregnancy has been shown to lead to mental retardation and other developmental abnormalities in infants2 > 250 mcg of biotin to maintain levels during pregnancy3 > 300 mg of DHA may help to improve cognitive development and visual acuity4-7† > The Prenate® Vitamin Family contains Metafolin®, which may help reduce the risk of neural tube defects, especially in those who have difﬁculty metabolizing folic acid8-10 Learn more at www.prenate.com and www.prenateperl.com. * The NHANES I and NHANES III surveys showed that from 1988-1994, 11.7% of Americans exhibited iodine deﬁciency, which represents a 4.5-fold increase compared with 1971-1974.1 † Supportive, but not conclusive, research shows that consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease. One capsule of PRENATE ESSENTIAL™ provides 340 mg of omega-3 fatty acids, of which 300 mg are DHA. WARNING: Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6. Keep this product out of reach of children. In case of accidental overdose, call a doctor or poison control center immediately. WARNING: Ingestion of more than 3 grams of omega-3 fatty acids (such as DHA) per day has been shown to have potential antithrombotic effects, including an increased bleeding time and International Normalized Ratio (INR). Administration of omega-3 fatty acids should be avoided in patients taking anticoagulants and in those known to have an inherited or acquired predisposition to bleeding. Please see full Product Information on reverse. With With them all the way DESCRIPTION: PRENATE ESSENTIAL™ is a prescription prenatal/postnatal multivitamin/mineral/essential fatty acid softgel. Each softgel is blue-green in color, opaque, and imprinted with “Prenate” on one side. Vitamin C 85 mg 142% Vitamin D3 200 IU 50% Vitamin E 10 IU 33% Vitamin B6 25 mg 1250% Folate 1 mg 250% (L-methylfolate as Metafolin 600 mcg) (folic acid, USP 400mcg) 12 mcg 200% Vitamin B12 Biotin 250 mcg 83% Calcium 140 mg 14% (calcium carbonate) 28 mg 156% Iron (ferrous fumarate) Iodine (potassium iodide) 150 mcg 100% Magnesium 45 mg 11% (magnesium oxide) Docosahexaenoic Acid (DHA) 300 mg † Eicosapentaenoic Acid (EPA) 40 mg † (from 340 mg omega-3 fatty acids from ﬁsh oil) 142% 50% 33% 1000% 125% 150% 83% 11% 156% 100% 10% † † Other Ingredients: ﬁsh oil, gelatin, hydrogenated vegetable oil, glycerin, sorbitol, beeswax, soy lecithin, titanium dioxide, vanillin, FD&C blue No. 1, propylene glycol, hypromellose. Have your say about what appears in INDICATIONS: PRENATE ESSENTIAL is a multivitamin/mineral/essential fatty acid nutritional supplement indicated for use in improving the nutritional status of women throughout pregnancy and in the postnatal period for both lactating and non-lactating mothers. PRENATE ESSENTIAL can also be beneﬁcial in improving the nutritional status of women prior to conception. CONTRAINDICATIONS: PRENATE ESSENTIAL is contraindicated in patients with a known hypersensitivity to any of the ingredients. WARNING: Ingestion of more than 3 grams of omega-3 fatty acids (such as DHA) per day has been shown to have potential antithrombotic effects, including an increased bleeding time and International Normalized Ratio (INR). Administration of omega-3 fatty acids should be avoided in patients taking anticoagulants and in those known to have an inherited or acquired predisposition to bleeding. WARNING: Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6. Keep this product out of reach of children. In case of accidental overdose, call a doctor or poison control center immediately. Would you like to join our panel of Clinical Reactors? PRECAUTIONS: Folic acid alone is improper therapy in the treatment of pernicious anemia and other megaloblastic anemias where vitamin B12 is deﬁcient. Folic acid in doses above 1 mg daily may obscure pernicious anemia in that hematologic remission can occur while neurological manifestations progress. ADVERSE REACTIONS: Allergic sensitization has been reported following both oral and parenteral administration of folic acid. DOSAGE AND ADMINISTRATION: Before, during, and/or after pregnancy, one softgel daily or as directed by a physician. HOW SUPPLIED: Unit-dose packs of 30 softgels NDC # 59630-419-30 KEEP THIS AND ALL DRUGS OUT OF THE REACH OF CHILDREN. Store at 20°-25°C (68°-77°F). Excursions permitted to 15°-30°C (59°-86°F). [See USP Controlled Room Temperature] For inquiries call 1-800-849-9707 extension 1454. U.S. Patents #5,997,915; #6,254,904; #6,011,040; #6,451,360; #6,673,381; #6,808,725; #6,441,168 Metafolin® is a registered trademark of Merck KGaA, Darmstadt, Germany. PNE-PI-1 Rev. 02/10 Manufactured for: Manufactured by: Catalent Pharma Solutions, Swindon, UK Made in the United Kingdom Atlanta, Georgia USA 30328 References: 1. Hollowell JG, Staehling NW, Hannon WH, et al. Iodine nutrition in the United States. Trends and public health implications: iodine excretion data from National Health and Nutrition Examination Surveys I and III (1971-1974 and 1988-1994). J Clin Endocrinol Metab. 1998;83(10):3401-3408. 2. Zimmermann MB. Iodine deﬁciency. Endocr Rev. 2009;30(4):376-408. 3. Mock DM. Marginal biotin deﬁciency is common in normal human pregnancy and is highly teratogenic in mice. J Nutr. 2009;139(1):154-157. 4. Horrocks LA, Yeo YK. Health beneﬁts of docosahexaenoic acid (DHA). Pharmacol Res.1999;40(3):211-225. 5. Uauy R, Hoffman DR, Mena P, Llanos A, Birch EE. Term infant studies of DHA and ARA supplementation on neurodevelopment: results of randomized controlled trials. J Pediatr. 2003;143(suppl 4):S17-S25. 6. Birch EE, Garﬁeld S, Hoffman DR, Uauy R, Birch DG. A randomized controlled trial of early dietary supply of long-chain polyunsaturated fatty acids and mental development in term infants. Dev Med Child Neurol. 2000;42(3):174-181. 7. Agostoni C, Trojan S, Bellù R, Riva E, Giovannini M. Neurodevelopmental quotient of healthy term infants at 4 months and feeding practice: the role of long-chain polyunsaturated fatty acids. Pediatr Res. 1995;38(2):262-266. 8. Dietary supplement fact sheet: folate. National Institutes of Health Web site. http://ods.od.nih.gov/factsheets/folate.asp. Accessed March 15, 2010. 9. March of Dimes® Quick Reference. Folic acid. March of Dimes® Web site. http://www.marchofdimes.com/professionals/14332_1151.asp. Accessed March 15, 2010. 10. Metafolin®: about Metafolin®. Merck KGaA Web site. http://www.metafolin.com/servlet/PB/menu/1784410/index.html. Accessed March 15, 2010. Prenate® is a registered trademark and Prenate Essential™ is a trademark of Shionogi Pharma, Inc. Metafolin® is a registered trademark of Merck KGaA, Darmstadt, Germany. © 2010 Shionogi Pharma, Inc. Atlanta, Georgia. All rights reserved. PRE.03.10.019.02 If you’re in active ob/gyn practice, we’d like your opinion on articles we’ve invited. As a Clinical Reactor, you’ll play an active role in helping Editor-in-Chief Charles J Lockwood, MD, MHCM, and our distinguished Editorial Advisory Board keep Contemporary OB/GYN relevant and practical by occasionally reviewing prepublication drafts of upcoming articles. To join the Clinical Reactor panel e-mail: contemporaryobgyn@mail.contemporaryobgyn.net CLINICIAN TO CLINICIAN continued from page 30 Rules also govern billing and payment. Payment schedules are linked to procedure codes, which physicians must link to appropriate diagnoses. Errors can subject physicians to ﬁ nes and criminal action. Te 2011 Current Procedural Terminology manual is 630 pages. Te International Classiﬁcation of Diseases Ninth Revision (ICD-9) is even longer. Rules governing hospital practice and payment are still more elaborate. The consequences In the end, it is increasingly difficult for physicians to manage practices that comply with payors’ and regulators’ requirements. Because institutions must do this, they must exert control over physicians’ practice patterns. In 2004, 65.5% of physicians were self-employed, 8.4% were employed by other physicians, and 26.1% were employed by institutions.13 Near eradication of private practice seems inevitable. Medical industrialization and bureaucratization will continue as technology advances, regardless of how medical care is financed. Although more illnesses will yield to accurate diagnosis and effective, standardized treatment, physicians will become less creative, will use less judgment in practice, and will alter their focus from the pursuit of excellence to the avoidance of mistakes. Physicians are losing importance and standing in the eyes of patients, hospitals, employers, and payors. For example, most patients will switch from a physician with whom they have had a longstanding relationship to a new one if the former is out-of-network and costs more. Thus, physicians’ interchangeability also reduces their income. Between 1995 and 2003, physicians’ income fell by 7%, adjusting for inflation.14 Most physicians soon will be employees of large organizations in which they are not shareholders. Although this would be inevitable even without government involvement, the government is aware of the potential of large groups to control costs and The chief attribute that will differentiate clinicians moving forward will be interpersonal skills. 34 CONTEMPORARYOBGYN.NET JULY 2011 possibly quality, and is spurring the shift with the Patient Protection and Affordable Care Act of 2010, which will force physicians into accountable care organizations. Electronic medical records (EMR) will incorporate care algorithms, which will direct compliance. They will prompt physicians to obtain certain information or to employ certain treatments. EMRs will be necessary to cope with requirements of regulators and payors. Such sophisticated EMRs may be beyond the financial reach of independent physicians, providing another impetus for them to become employees. High-level cognitive skills, such as creativity and judgment, will be reserved for use in research positions. Only a small number of elite schools will train medical leaders, while the others will train clinicians. Medical leaders will be minimally involved in patient care. Clinicians will view their work as a livelihood rather than as a career. They already are more inclined to choose medical specialties that offer short, controllable work hours.15 Highly ambitious people who are willing to invest long hours for the possibility of great reward will enter alternative professions such as investment banking, law, or computer science rather than clinical medicine. Physicians will increasingly regard themselves as workers rather than professionals. The American Medical Association has cautiously endorsed physicians’ unions, preferring the term “independent bargaining units.”16 Physician strikes may occur here, as they have abroad17-19, and their political views likely will continue to move to the left. 20 The one way in which physicians can continue to vary is in their ability to attract patients and persuade them to follow treatment plans. In other words, the chief attribute that will differentiate clinicians moving forward will be interpersonal skills. Perhaps, if nothing else, this inevitable climactic shift in medicine will improve bedside manner. DR JACOBS is chair, obstetrics and gynecology, Flushing Hospital Medical Center, Flushing, New York; professor, obstetrics, gynecology, and reproductive medicine, and affiliated faculty, Center for Medical Humanities, Compassionate Care and Bioethics, Stony Brook University School of Medicine, Stony Brook, New York. He has no conflicts of interest, real or apparent, with regard to the content of this article. The opinions expressed in this article are those of Dr Jacobs, and do not reflect the opinions of the institutions with which he is affiliated or those of the publishers and editors of Contemporary OB/GYN. CLINICIAN TO CLINICIAN Don’t Miss A Single Issue. REFERENCES 1. National Cancer Institute. SEER Cancer Statistics Review 1973-1999. http://www.mindfully.org/ Health/2002/SEER-Cancer1950-99.htm. Accessed June 17, 2011. 2. Zuger A. Dissatisfaction with medical practice. N Engl J Med. 2004;350(1):69-75. 3. Hadley J, Mitchell JM. Efffects of HMO market penetration on physicians’ work effort and satisfaction. Health Aff (Millwood). 1997;16(6):99-111. Translating Science into Sound Clinical Practice New techniques for treating SUI 5. Percutaneous coronary interventions (PCI) in New York State 2006-2008. New York State Department of Health Web site. http://www.nyhealth.gov/statistics/diseases/cardiovascular/docs/ pci_2006-2008.pdf. Published December 2010. Accessed June 15, 2011. 6. Copeland GP, Sagar P, Brennan J, et al. Risk-adjusted analysis of surgeon performance: a 1-year study. Br J Surg. 1995;82(3):408-411. 9. Jamtvedt G, Young JM, Kristoffersen DT, Thomson O’Brien MA, Oxman AD. Audit and feedback: effects on professional practice and health care outcomes. Cochrane Database Syst Rev. 2003;(3):CD000259. 10. East J, Krishnamurthy P, Freed B, Nosovitski G. Impact of a diabetes electronic management system on patient care in a community clinic. Am J Med Qual. 2003;18(4):150-154. 11. Tung Y, Duffy LC, Gyamfi JO, et al. Improvements in immunization compliance using a computerized tracking system for inner city clinics. Clin Pediatr (Phila). 2003;42(7):603-611. 12. Weber M. Economy and Society. Roth G, Wittich C, eds. Berkeley, CA: University of California Press; 1978:956-962. 13. Kane CK; American Medical Association Center for Health Policy Research. Physician marketplace report. http://www.ama-assn.org/resources/doc/health-policy/pmr-022004.pdf. Published February 2004. Accessed June 15, 2011. 14. Tu HT, Ginsburg PB. Losing ground: physician income, 1995–2003. Center for Studying Health System Change. Tracking Report No. 15. http://hschange.org/CONTENT/851/851.pdf. Published June 2006. Accessed June 21, 2011. 15. Dorsey ER, Jarjoura D, Rutecki GW. Influence of controllable lifestyle on recent trends in specialty choice by US medical students. JAMA. 2003;290(9):1173-1178. 16. Greenhouse S. Angered by H.M.O.’s treatment, more doctors are joining unions. The New York Times. February 4, 1999:A1. PAGE 28 Understanding CDC’s new strep B guidelines PAGE 6 Genes determine severe morning sickness sufferers PAGE 10 VOLUME 56, NUMBER 1 7. Sommer F, Ehsan A, Klotz T, Haupt G, Caspers H-P, Engelmann U. Comparison of individual urologists’ performance. Eur Urol. 2001;39(4):369-374. 8. Berenguer CM, Ochsner MG Jr, Lord SA, Senkowski CK. Improving surgical site infections: using National Surgical Quality Improvement Program data to institute Surgical Care Improvement Project protocols in improving surgical outcomes. J Am Coll Surg. 2010;210(5):737-741, 741-743. JANUARY 2011 ContemporaryOBGYN.net 4. Singh GK, Yu SM. Infant mortality in the United States: trends, differentials, and projections, 1950 through 2010. Am J Pub Health. 1995;85(7):957-964. Are infants born under midwife care at higher risk for death? PAGE 14 t 1SPCMFNTPMWJOH DMJOJDBMBSUJDMFT t 1SBDUJDBMJOGPSNBUJPO GSPNýFMEFYQFSUT t $PWFSBHFPG EJBHOPTJTUSFBUNFOU BOEQSBDUJDF NBOBHFNFOU t 6QUPEBUFDMJOJDBM OFXTBOESFTFBSDI “Contemporary OB/GYN is packed with critical, useful information that OB/GYNs can use to improve their practices, even save lives.” 17. Baer N. Despite some PR fallout, proponents say MD walkouts increase awareness and may improve health care. Can Med Assoc J. 1997;157(9):1268-1271. 18. Athens News Agency: News in English (AM), 98-12-22. Athens hospital physicians’ workstoppages over payments. http://www.hri.org/news/greek/apeen/1998/98-12-22.apeen.html. Published December 1998. Accessed June 21, 2011. 19. Harrison M. A profession in conflict: Union militancy among Israeli physicians. Current Research on Occupations and Professions. 1991;6:179-199. 20. Ackermann RT, Carroll AE. Support for national health insurance among U.S. physicians: a national survey. Ann Intern Med. 2003;139(10):795-801. JULY 2011 CONTEMPORARY OB/GYN Translating Science into Sound Clinical Practice ContemporaryOBGYN.net 35 Pregnancy Complications ■ Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) SPONSORS: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Heart, Lung, and Blood Institute (NHLBI); and Office of Research on Women’s Health (ORWH) IDENTIFIER: NCT01322529 ■ Progesterone for the Management of Preterm, Premature Rupture of the Membranes: A Randomized, Controlled Trial SPONSOR: Stanford University IDENTIFIER: NCT01050647 ■ Prenatal and Postnatal Studies of Interventions for Prevention of Mother-To-Child Transmission SPONSORS: International Maternal Pediatric Adolescent AIDS Clinical Trials Group; National Institute of Allergy and Infectious Diseases (NIAID); and Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) IDENTIFIER: NCT00028145 ■ Ribavirin Pregnancy Registry Kendle International; Aurobindo; Genentech; Sandoz Inc; Merck; Teva Pharmaceuticals USA; Three Rivers Pharmaceuticals; and Zydus Pharmaceuticals USA Inc IDENTIFIER: NCT00114712 SPONSORS: This list of US-based National Institutes of Health trials is derived from the NIH database and includes US phase III and IV clinical trials that are currently recruiting female participants. For information, view the complete database at http://ClinicalTrials.gov. Nutritional and Metabolic Disorders ■ Gestational Diabetes Mellitus and Cardiovascular Disease: The Role of Vascular Dysfunction SPONSOR: Brigham and Women’s Hospital IDENTIFIER: NCT00998712 ■ Role of Neural and Hormonal Regulation Factors on Insulin Secretion After Gastric Bypass Surgery SPONSORS: University of Cincinnati and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) IDENTIFIER: NCT00992901 ■ Celiac Disease Database University of Chicago IDENTIFIER: NCT01172665 SPONSOR: ■ Randall’s Plaque Study: Pathogenesis and Relationship to Nephrolithiasis SPONSORS: Indiana Kidney Stone Institute; Indiana University School of Medicine; and University of Chicago IDENTIFIER: NCT00169806 ■ Vitamin D, Diet and Activity Study (ViDA) Fred Hutchinson Cancer Research Center IDENTIFIER: NCT01240213 SPONSOR: ■ Continuous Glucose Monitoring in Pregnant Women Undergoing Betamethasone Therapy SPONSOR: Stanford University IDENTIFIER: NCT01165775 ■ UCB Antiepiieptic Drugs (AED) Pregnancy Registry (Formerly the Keppra Pregnancy Registry) SPONSORS: Kendle International and UCB Inc IDENTIFIER: NCT00345475 ■ Metformin Versus Insulin in Pregnant Women With Type 2 Diabetes SPONSOR: The University of Texas Health Science Center, Houston IDENTIFIER: NCT00678080 ■ Biological Markers of Disease in the Prediction of Preterm Delivery, Preeclampsia and Intra-Uterine Growth Retardation: A Longitudinal Study SPONSORS: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and National Institutes of Health Clinical Center (CC) IDENTIFIER: NCT00340899 ■ Ferumoxytol for the Episodic Treatment of Iron Deficiency Anemia SPONSOR: AMAG Pharmaceuticals Inc IDENTIFIER: NCT01114217 ■ Effect of Vitamin D Supplementation on Inflammation and Cardiometabolic Risk Factors in Obese Adolescents SPONSOR: Stanford University IDENTIFIER: NCT01217840 ■ Preventing Fetal Body and Brain Size Reduction in Low-income Smoking Mothers: A Randomized Clinical Trial SPONSOR: University of South Florida IDENTIFIER: NCT01248260 ■ Vitamin B6 Effects for Women Taking Birth Control Pills SPONSOR: University of Florida IDENTIFIER: NCT01128244 JULY 2011 CONTEMPORARY OB/GYN 35A Bio-Oil® is a skincare oil that helps improve the appearance of scars, stretch marks and uneven skin tone. It contains natural oils, vitamins and the breakthrough ingredient PurCellin Oil™. For comprehensive product information and results of clinical trials, please visit bio-oil.com. Bio-Oil is the No.1 selling scar and stretch mark product in 11 countries. $11.99 (2fl.oz.). ULTRASOUND SAFETY Fetal ultrasound How to put safety first Understanding the potential risks associated with fetal ultrasound and the key safety issues are the foundation for optimal use of this important imaging modality. BY LAURA HOUSTON, MD, AND ROGER NEWMAN, MD T he number of indications for ultrasound examination during pregnancy is rising. In addition, experts have expanded the gestational age range for which fetal ultrasound assessment is appropriate to include the ﬁrst trimester. Considering the increased use of ultrasound, should clinicians heighten their concern regarding the safety of this technique? Are there ways to minimize potential risks to the fetus? What do clinicians need to know about the safety of this important imaging modality during pregnancy? Te answers are not as straightforward as one might think. This article reviews the potential impact of ultrasound on the fetus and ways through which the sonographer can minimize risk and maximize safety. A key element of this is understanding how to use the output display standard (ODS) during all obstetric ultrasound examinations. Te ODS, which is displayed on screen during 36 CONTEMPORARYOBGYN.NET JULY 2011 an ultrasound examination, provides an approximation of biologic risk generated during the exam. It is currently the safety mechanism in place for all ultrasound examinations, and the American College of Obstetricians and Gynecologists (ACOG) supports its use.1 Potential bioeffects of ultrasound Ultrasound diﬀers from other imaging modalities in that it is nonionizing and, thus, considered safer for fetal evaluation.2 Nevertheless, obstetric ultrasound may produce biologic changes through 1 of 2 mechanisms: thermal or nonthermal. Thermal bioeffects refer to biologic changes associated with a rise in temperature in the targeted tissue.3 Although some ultrasound waves ref lect off the exposed tissue and are used for the generation of images, others are absorbed by the tissue and the energy is converted into heat. 3 T is is GETTY IMAGES/COMSTOCK IMAGES/THINKSTOCK ULTRASOUND SAFETY important given the potential teratogenicity of fetal exposure to signiﬁcant temperature elevations.4 Nonthermal bioeffects, frequently referred to as mechanical bioeTects, are biologic changes resulting from ultrasound insonation without a pathophysiologic rise in temperature. Although this concept is somewhat abstract, it nonetheless appears to be relevant in fetal ultrasound safety. 5 Examples of mechanical bioeTects observed with diagnostic ultrasound include cavitation, acoustic streaming, radiation forces, and free-radical generation. The term cavitation, which is frequently encountered when investigating mechanical bioeffects, refers to the interaction between an ultrasound wave and a gas bubble.5 Ultrasound waves can cause gas bubbles to move, expand, or collapse. At the cellular level, even slight movement of gas bubbles can potentially disrupt cellular connections. Output display standard ﬀe ODS was created by the American Institute of Ultrasound in Medicine and the National Electrical Manufacturers Association to approximate the risks for thermal and mechanical bioeTects encountered during an ultrasound examination. As noted earlier, use of the ODS is supported by ACOG1 as well as by the US Food and Drug Administration (FDA).6 ﬀe ODS includes the thermal index (TI) and the mechanical index (MI), which are calculated by the ultrasound machine and displayed in a corner on screen if the machine is capable of generating a TI or MI greater than 1. ﬀe higher the TI or MI value, the greater the probability of a thermal or mechanical bioeTect.6 As a general rule, an index value less than 1 is considered safe (Table 1).6 Displaying the index number on the screen allows the clinician or sonographer to monitor the number while scanning. If the index value is greater JULY 2011 CONTEMPORARY OB/GYN 37 ULTRASOUND SAFETY TABLE 1. Use of the ODS for maintenance of safe index values during ultrasound Abbreviation displayed ODS Goal for safety Need to consider adjustments Thermal index TI <1 >1 Mechanical index MI <1 >1 Abbreviations: MI, mechanical index; ODS, output display standard; TI, thermal index. Information from Barnett SB et al.6 POWER POINTS Although ultrasound is nonionizing radiation, it has the potential to produce thermal and mechanical bioeffects that warrant caution. The Output Display Standard (ODS) approximates the risks of thermal and mechanical bioeffects of ultrasound exposure. The ODS ideally should always be less than 1. than 1, the sonographer can make necessary adjustments. Minimizing the exposure time, changing the ultrasound mode, or adjusting such settings as the power output all can aﬁect the TI or MI values (Table 2).6,7 Te FDA is responsible for designating an upper limit for the allowable output of ultrasound machines. In 1976, this value was set fairly low, at 94 mW/cm 2 , for fetal exposure.6 As technology improved, clearer images and Doppler capability required more powerful output settings. To permit clinical use of these newer ultrasound machines, the FDA increased the allowable output for obstetric ultrasound machines in 1992 to 720 mW/cm2: nearly 8 times higher than the previous limit.6 Currently, instead of ultrasound safety being regulated strictly by the FDA, the responsibility rests largely with the sonographer, who is required to ensure that the limits of the ODS are not exceeded during the ultrasound examination.6 Evidence for ultrasound exposure causing biologic risk Te available evidence on fetal development and neonatal outcomes after ultrasound exposure is strongly reassuring. Much of the research that raises concerns about ulTABLE 2. Appropriate adjustments if the TI or MI exceeds 1 Shorten examination time Change to lower output mode (such as changing Doppler to standard B-mode) Adjust ultrasound settings • Power output • Area of color flow Abbreviations: MI, mechanical index; TI, thermal index. Information from Barnett SB, et al6; Abramowicz JS.7 38 CONTEMPORARYOBGYN.NET JULY 2011 trasound safety was conducted in animals. A 2006 study addressed the possibility that ultrasound exposure might affect the migration of cerebral neurons. 8 The authors of the study exposed pregnant mice late in gestation to ultrasound delivered at 6.7 MHz, a slightly higher frequency than that typically used in humans. Total exposure over a 3-day period ranged from 5 minutes to 420 minutes. Longer exposure times correlated with decreased migration of neurons, which was signiﬀcant for all exposure times longer than 15 minutes. 8 Given the exposure conditions used, the investigators did not believe that temperature was the likely mechanism. Instead they proposed that mechanical eﬁects altered the cellular connections.8 Other studies in mice suggested decreased birth weight in ultrasound-exposed subjects, although follow-up growth at 6 weeks of age was similar to that of unexposed controls.9 Investigators reported postnatal lung hemorrhage in mice in 1990, leading to investigations in prenatal subjects.10 Investigators also found hemorrhages in the brains of fetal mice exposed to pulsed ultrasound.11 In contrast, data in humans generally have not shown a link between prenatal ultrasound exposure and adverse clinical outcomes. Between 1992 and 1994, researchers published a series of papers based on the results from 2 randomized clinical trials in Norway.12-15 Tey assessed clinical outcomes, including body weight and height, school performance, dyslexia, vision, hearing, and speech development in more than 2,000 children who had been either exposed or not exposed to ultrasound at 19 weeks’ and 32 weeks’ gestation. The assessment, which took place when the children were 7, 8, or 9 years of age, found no diﬁerences in any of the clinical outcomes between the exposed and the unexposed children. Similar results from a randomized clinical trial in Sweden published between 1997 and 1998 again demonstrated no diﬁerences in weight, height, vision, hearing, or neurological development between children ex- A smart combination to support prenatal health* t A complete multivitamin plus a DHA/EPA liquid gel with key nutrients to support prenatal health* t From One A Day®, a brand women trust t Conveniently available over the counter and may be more affordable than some branded prescription prenatal vitamins Recommend DHA=docosahexaenoic acid. EPA=eicosapentaenoic acid. *This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. © 2011 Bayer HealthCare LLC April 2011 41772-6923 Changing expectations ULTRASOUND SAFETY POWER POINTS The sonographer is responsible for ultrasound safety. Results of studies in fetal animals link ultrasound exposure with adverse developmental outcomes. Data from human studies have not shown an association between adverse clinical outcomes and prenatal ultrasound exposure. posed to ultrasound at 15 weeks and unexposed children, all of whom were assessed at 8 or 9 years of age.16,17 Other studies have shown no association between ultrasound exposure and childhood cancer.18-20 Moreover, investigators have noted similarities in birth weights, Apgar scores, neonatal intensive care unit admissions, and other outcomes among ultrasound-exposed and -unexposed subjects.21-23 Interestingly, 1 clinical outcome for which a possible association persists is non-right-handedness. In a follow-up of the previously mentioned Norwegian trials, 12-15 the odds of non-right-handedness in children exposed to ultrasound at 19 weeks’ and 32 weeks’ gestation were higher than those of nonexposed children (odds ratio [OR], 1.32; 95% conﬁdence interval [CI], 1.02-1.71).24 In this study, nonright-handedness included children who used both hands equally or their leT hand predominantly. Follow-up of the Swedish trial16,17 found no diﬀerence in non-right-handedness between the ultrasound-screened and the nonscreened groups overall, but reported an increased OR of non-right-handedness among boys (OR, 1.33; 95% CI, 1.02-1.74).25 A meta-analysis of these trials found no overall diﬀerence between the ultrasoundexposed and -unexposed groups; however, a subgroup analysis of males revealed an increased risk for non-right-handedness among the ultrasound-exposed children (OR, 1.26; 95% CI, 1.03-1.54). 26 Although this association does not appear to be particularly strong, other studies have yet to disprove the ﬁnding. Doppler and ultrasound safety Frequent assessment of the ODS is particularly important during Doppler ultrasound examinations. The output potential of ultrasound varies according to mode. Because Doppler uses higher acoustic power focused on a speciﬁc fetal volume, its output is higher than that of standard ultrasound modes. A good example is the use of middle cerebral artery (MCA) Doppler ultrasound for detection of fetal anemia. Bone has a 40 CONTEMPORARYOBGYN.NET JULY 2011 higher absorption potential than other tissues. fus, MCA Doppler involves the use of a higher output ultrasound setting, which is focused on the tissue with the high ultrasound absorption potential. f is is not to say that a medically indicated MCA Doppler ultrasound examination should not be performed. On the contrary, the risk-to-beneﬁt ratio generally favors use of this noninvasive approach with a challenging diagnosis. It is simply important to bear in mind the potential impact of the imaging modality being used and to recognize the safety guidelines that are in place for its use. A 2007 study supported the higher acoustic output potential of Doppler ultrasound over 2-dimensional imaging. Researchers recorded TI during 63 ultrasound examinations, using standard B-mode or Doppler imaging. 27 The mean TI was 0.3 with B-mode sonography, 0.8 with Doppler color f low imaging, and 1.5 with pulsedwave Doppler imaging. fe study demonstrated that a mean TI greater than 1 can occur during a Doppler ultrasound examination, particularly with pulsed-wave Doppler. In 2009, a study in chicks showed an effect of pulsed Doppler ultrasound on memory and learning. Investigators exposed chicks either to standard B-mode ultrasound or to pulsed Doppler. fey noted no diﬀerences in memory in the B-mode group aTer as long as 10 minutes’ exposure; however, chicks demonstrated decreased shortand long-term memory aTer just 4 minutes of exposure to pulsed Doppler ultrasound.28 Overall, studies in humans are reassuring with respect to clinical outcomes aTer Doppler exposure. 29 However, researchers reported concern regarding growth restriction and Doppler exposure in 1 clinical trial in which women were randomized to receive either a single ultrasound imaging study at 18 weeks’ gestation (the regular group) or both ultrasound imaging and continuous-wave Doppler f low studies at 18, 24, 28, 34, and 38 weeks’ gestation (the intensive group).30 fe researchers reported a significant association with growth restriction in the intensively scanned group, ULTRASOUND SAFETY with a higher proportion of birth weights under the tenth percentile (relative risk [RR], 1.35; 95% CI, 1.09-1.67; P=.006) and under the third percentile (RR, 1.65; 95% CI, 1.09-2.49; P=.020). Follow-up of the oﬁspring at ages 1, 2, 3, 5, and 8 years, however, revealed similar growth between the 2 groups.31 Te investigators also evaluated developmental outcomes, including language, social, and motor assessments, and found no differences between the groups. Conclusions Data on the safety of fetal ultrasound exposure generally are reassuring. However, most studies on the subject were conducted prior to 1990, during a period in which the allowable output potential for ultrasound equipment was relatively reduced. Furthermore, at that time, obstetric ultrasound was not performed as frequently in either highrisk or low-risk pregnancies as it is today. Currently, in spite of the lack of deﬀnitive evidence regarding the beneﬀts of obstetric ultrasound screening in low-risk populations, a single targeted “anomaly” scan at 18 weeks’ to 20 weeks’ gestation is part of routine practice. 32 Given the higher levels of energy generated during contemporary ultrasound examinations, new randomized studies to assess the risks are warranted, but would now be more difcult to perform because the routine use of ultrasound in pregnancy has become the de facto standard of care in the US. Studies conducted to evaluate the eﬁect of Doppler ultrasound also are needed. Unfortunately, the level of knowledge regarding ultrasound safety issues appears to be less than desirable. In a 2005 survey of attendees of European postgraduate obstetric ultrasound courses, only 22% and 11% of the participants could explain the TI and MI, respectively, and only 28% could locate this information on the ultrasound screen.33 A similar survey of American ultrasound operators conducted in 2007 revealed comparable results: 17.7% and 3.8% of the participants could describe the TI or MI, respectively, and 20.8% could locate this information on the display.34 TABLE 3. Key points for ultrasound safety • The operator is responsible for ultrasound safety. • Look at the ODS while doing ultrasound. • The ODS should be less than 1. • Use extra care with new machines; evidence regarding their use is limited. • Be aware of higher output with Doppler ultrasound, particularly during the first trimester. Abbreviation: ODS, output display standard. Overall, ultrasound appears to be safe. However, clinicians should realize the limitations in knowledge about the absolute safety of the technology and should strive to ensure that users of the technology routinely employ safety mechanisms, such as the ODS. Ultrasound safety is the responsibility of the sonographer (Table 3). Sonographers should review TI and MI whenever an ultrasound examination is performed. If either index value is greater than 1, the duration or the settings of the examination should be adjusted, particularly if it involves Doppler ultrasound. Safety during imaging can be achieved by adhering to a radiologic principle known as ALARA, which stands for As Low As Reasonably Achievable. T is implies using the minimum duration and the lowest possible ultrasound exposure setting to obtain the diagnostic information needed to complete the examination.6,35 As ultrasound technology improves, new applications and more powerful machines are certain to be developed. We hope these advancements also will yield machines with minimal risks, maximum safety, and greater diagnostic potential. POWER POINTS The acoustic output potential of Doppler ultrasound surpasses that of conventional ultrasound. Although Doppler ultrasound generally is considered safe, 1 study suggested intensive fetal Doppler exposure may affect birth weight. Because data about the safety of fetal ultrasound are not abundant, clinicians and sonographers should err on the side of caution when ordering and performing prenatal imaging. DR HOUSTON is a first-year maternal-fetal medicine fellow and DR NEWMAN is vice chair, Academic Affairs and Women’s Health Research, Department of MaternalFetal Medicine at the Medical University of South Carolina in Charleston. Neither author reports any conflicts of interest, real or apparent, with regard to the content of this article. REFERENCES 1. American College of Obstetricians and Gynecologists. New ultrasound output display standard. ACOG Committee Opinion Number 180, November 1996. Committee on Obstetric Practice. Int J Gynaecol Obstet. 1997;57(2): 227-228. JULY 2011 CONTEMPORARY OB/GYN 41 ULTRASOUND SAFETY 2. American College of Obstetricians and Gynecologists Committee on Obstetric Practice. Guidelines for diagnostic imaging during pregnancy. ACOG Committee Opinion Number 299, September 2004 (replaces Number 158, September 1995). Obstet Gynecol. 2004;104(3):647-651. 3. Duck FA, Starritt HC. A study of the heating capabilities of diagnostic ultrasound beams. Ultrasound Med Biol. 1994;20(5):481-492. 4. Edwards MJ. Review: hyperthermia and fever during pregnancy. Birth Defects Res A Clin Mol Teratol. 2006;76(7):507-516. 20. Shu XO, Jin F, Linet MS, et al. Diagnostic X-ray and ultrasound exposure and risk of childhood cancer. Br J Cancer. 1994;70(3):531-536. 21. Lyons EA, Dyke C, Toms M, Cheang M. In utero exposure to diagnostic ultrasound: a 6-year follow-up. Radiology. 1988;166(3):687-690. 22. Smith CB. Birth weights of fetuses exposed to diagnostic ultrasound. J Ultrasound Med. 1984;3(9):395-396. 5. Stratmeyer ME, Greenleaf JF, Dalecki D, Salvesen KA. Fetal ultrasound: mechanical effects. J Ultrasound Med. 2008;27(4):597-605. 23. Bakketeig LS, Eik-Nes SH, Jacobsen G, et al. Randomised controlled trial of ultrasonographic screening in pregnancy. Lancet. 1984;2(8396):207-211. 6. Barnett SB, Ter Haar GR, Ziskin MC, Rott HD, Duck FA, Maeda K. International recommendations and guidelines for the safe use of diagnostic ultrasound in medicine. Ultrasound Med Biol. 2000;26(3):355-366. 24. Salvesen KA, Vatten LJ, Eik-Nes SH, Hugdahl K, Bakketeig LS. Routine ultrasonography in utero and subsequent handedness and neurological development. BMJ. 1993;307(6897):159-164. 7. Abramowicz JS. Ultrasound in obstetrics and gynecology: is this hot technology too hot? J Ultrasound Med. 2002;21(12):1327-1333. 25. Kieler H, Axelsson O, Haglund B, Nilsson S, Salvesen KA. Routine ultrasound screening in pregnancy and the children’s subsequent handedness. Early Hum Dev. 1998; 50(2):233-245. 8. Ang ES Jr, Gluncic V, Duque A, Schafer ME, Rakic P. Prenatal exposure to ultrasound waves impacts neuronal migration in mice. Proc Natl Acad Sci USA. 2006;103(34):12903-12910. 9. Hande MP, Devi PU. Effect of in utero exposure to diagnostic ultrasound on the postnatal survival and growth of mouse. Teratology. 1993;48(5):405-411. 10. Child SZ, Hartman CL, Schery LA, Carstensen EL. Lung damage from exposure to pulsed ultrasound. Ultrasound Med Biol. 1990;16(8):817-825. 11. Dalecki D, Child SZ, Raeman CH, Cox C. Hemorrhage in murine fetuses exposed to pulsed ultrasound. Ultrasound Med Biol. 1999;25(7):1139-1144. 12. Salvesen KA, Jacobsen G, Vatten LJ, Eik-Nes SH, Bakketeig LS. Routine ultrasonography in utero and subsequent growth during childhood. Ultrasound Obstet Gynecol. 1993;3(1):6-10. 13. Salvesen KA, Bakketeig LS, Eik-Nes SH, Undheim JO, Økland O. Routine ultrasonography in utero and school performance at age 8-9 years. Lancet. 1992;339(8785): 85-89. 14. Salvesen KA, Vatten LJ, Jacobsen G, et al. Routine ultrasonography in utero and subsequent vision and hearing at primary school age. Ultrasound Obstet Gynecol. 1992;2(4):243-244, 245-247. 15. Salvesen KA, Vatten LJ, Bakketeig LS, Eik-Nes SH. Routine ultrasonography in utero and speech development. Ultrasound Obstet Gynecol. 1994;4(2):101-103. 16. Kieler H, Haglund B, Waldenström U, Axelsson O. Routine ultrasound screening in pregnancy and the children’s subsequent growth, vision and hearing. Br J Obstet Gynaecol. 1997;104(11):1267-1272. 17. Kieler H, Ahlsten G, Haglund B, Salvesen K, Axelsson O. Routine ultrasound screening in pregnancy and the children’s subsequent neurologic development. Obstet Gynecol. 1998;91(5 pt 1):750-756. 18. Kinnier Wilson LM, Waterhouse JA. Obstetric ultrasound and childhood malignancies. Lancet. 1984;2(8410):997-999. 19. Cartwright RA, McKinney PA, Hopton PA, et al. 42 Ultrasound examinations in pregnancy and childhood cancer. Lancet. 1984;2(8410):999-1000. CONTEMPORARYOBGYN.NET JULY 2011 26. Salvesen KA, Eik-Nes SH. Ultrasound during pregnancy and subsequent childhood non-right handedness: a metaanalysis. Ultrasound Obstet Gynecol. 1999;13(4):241-246. 27. Sheiner E, Shoham-Vardi I, Pombar X, Hussey MJ, Strassner HT, Abramowicz JS. An increased thermal index can be achieved when performing Doppler studies in obstetric sonography. J Ultrasound Med. 2007;26(1):71-76. 28. Schneider-Kolsky ME, Ayobi Z, Lombardo P, Brown D, Kedang B, Gibbs ME. Ultrasound exposure of the foetal chick brain: effects on learning and memory. Int J Dev Neurosci. 2009;27(7):677-683. 29. Mason GC, Lilford RJ, Porter J, Nelson E, Tyrell S. Randomised comparison of routine versus highly selective use of Doppler ultrasound in low risk pregnancies. Br J Obstet Gynaecol. 1993;100(2):130-133. 30. Newnham JP, Evans SF, Michael CA, Stanley FJ, Landau LI. Effects of frequent ultrasound during pregnancy: a randomised controlled trial. Lancet. 1993;342(8876): 887-891. 31. Newnham JP, Doherty DA, Kendall GE, Zubrick SR, Landau LL, Stanley FJ. Effects of repeated prenatal ultrasound examinations on childhood outcome up to 8 years of age: follow-up of a randomised controlled trial. Lancet. 2004;364(9450):2038-2044. 32. LeFevre ML, Bain RP, Ewigman BG, Frigoletto FD, Crane JP, McNellis D. A randomized trial of prenatal ultrasonographic screening: impact on maternal management and outcome. RADIUS (Routine Antenatal Diagnostic Imaging with Ultrasound) Study Group. Am J Obstet Gynecol. 1993;169(3):483-489. 33. Maršál K. The output display standard: has it missed its target? Ultrasound Obstet Gynecol. 2005;25(3):211-214. 34. Sheiner E, Shoham-Vardi I, Abramowicz JS. What do clinical users know regarding safety of ultrasound during pregnancy? J Ultrasound Med. 2007;26(3):319-325. 35. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin Number 101, February 2009: Ultrasonography in pregnancy. Obstet Gynecol. 2009;113(2 pt 1):451-461. It All Comes Down to ONE ONE SCOPE. EVERY DIRECTION. ONE ENERGY SOURCE. INFINITE OPTIONS. ONE PORT. MULTIPLE INSTRUMENTS. ONE VISUALIZATION PLATFORM. ANY PROCEDURE. The ﬁrst deﬂectable-tip technology brings triangulation inside the patient. Newly engineered ports will revolutionize access by allowing more instruments and greater ﬂexibility. Versatile ultrasonic and advanced bipolar solutions including the new, ergonomically designed HALO™ PKS™ Cutting Forceps. A single video platform that’s compatible with any Olympus scopes, rigid or ﬂexible. TOGETHER WE CAN DO LESS LAPARO-ENDOSCOPIC SINGLE SITE (LESS) SURGERY For more information, visit olympusamerica.com/LESS or call 888-524-7266 © 2010 Gyrus ACMI, Inc. AD618-1210 WORKFORCE CHALLENGES An evolving specialty confronts workforce changes The specialty of obstetrics and gynecology is changing in terms of workforce needs and expectations. We hope this commentary will serve as a basis for ongoing dialogue within our profession as well as with patients and other stakeholders. BY ERIN E TRACY, MD, MPH, AND WILLIAM F RAYBURN, MD, MBA L ike many other specialties in medicine, the ﬁeld of obstetrics and gynecology faces numerous workforce challenges. Te demand for services is rising, the supply of physicians remains relatively constant, and gender and generational changes are having a signiﬁcant impact on the culture of practice. In addition, geographic maldistribution Have you prepared your practice of physicians continues to plague ob/gyn and yourself if a hospital comes as it does many other medical specialties. wooing? Take the right steps: Furthermore, both the impending changes in contemporaryobgyn.net/ healthcare delivery and the ever-present need practicetrend to contain costs can influence an evolving workforce. Anticipated physician shortage T he a c a d e m ic m e d ic a l c om mu n it y recognizes the need for an increased number of physicians in this country. In 2006, the Association of American Medical Colleges (AAMC) called for a 30% increase in graduates from medical schools in the 44 CONTEMPORARYOBGYN.NET JULY 2011 United States. According to a recent AAMC report, ﬁrst-year medical school enrollment will be 23% higher in 2014 than it was in 2002.1 Residency training positions, which are the prerequisite for practice, have grown slowly—about 1% per year—albeit mostly in primary care fields, and have not kept pace with either population growth or allopathic and osteopathic medical school enrollments.2 Compounding this issue is the fact that the number of active physicians approaching retirement age will nearly double in the next decade. 3 An analysis of demographic data from the American Congress of Obstetricians and Gynecologists (ACOG) reveals that the percentage of ob/gyns 55 years of age and older rose from 25% in 2002 to 35% in 2010 (Figure).4 Another contributing factor is the significant increase in the percentage of female physicians, who will occupy a greater propor- GETTY IMAGES/IMAGE SOURCE tion of part-time positions and will work fewer patient-care hours than their male counterparts.5 Several recent reports predict a likely shortage of physicians in at least 21 medical and surgical specialties. 6 Separate studies were conducted by the federal government 3 and the AAMC’s Center for Workforce Studies.7 The AAMC study examined various scenarios related to the change in supply and demand for physicians in the future.7 Under t he “most plausible scena rio,” the investigators projected a shortage of 159,300 physicians by the year 2025.7 It is noteworthy that these projections assume supply equals demand in the base year, yet we know that 65 million Americans reside in areas designated by the Health Resources and Services Administration as “health professional shortage areas.”8 The potential ramifications of a physician workforce shortage in ob/gyn could be profound. Specific sectors of our specialty, including urogynecology and oncology, might consequently require improved access to care. 9 A vicious cycle could ensue if physicians, compelled to see more patients or work longer hours to meet patient service needs, decide to eliminate certain aspects of their practice. For example, the aging population will require increased healthcare services, which would consequently affect the field of gynecology, depending on the practice type. Older patients are likely to have an increased need for the management of urinary incontinence, pelvic organ prolapse, and gynecologic malignancies. Professional liability also must be considered in the future workforce equation. According to the 2009 ACOG Survey on Professional Liability, between 2006 and 2008, 30.2% of physicians reported that they had decreased the number of highrisk obstetric patients that they treated and 8% stopped practicing obstetrics altogether because of the risk or fear of professional liability claims or litigation.10 Evolving conditions in ob/gyn practices and leadership Our specialty is undergoing a dramatic gender shift, with significant increases in the number and proportion of female ob/g yns. The percentage of female ob/ gyn residents increased from 58% in 1995 to 75% in 2005.11 According to a recent AAMC analysis, however, no corresponding growth has occurred in the number of JULY 2011 CONTEMPORARY OB/GYN 45 WORKFORCE CHALLENGES FIGURE . ACOG fellows age 55 or older 40% 35% 30% 25% 20% 15% 10% 5% 0% 2002 2005 2010 Year The proportion of obstetricians/gynecologists 55 years of age and older who are fellows in the American Congress of Obstetricians and Gynecologists increased from 25% in 2002 to 35% in 2010. From: Rayburn WF.4 Reprinted with permission. POWER POINTS By 2025, the number of physicians in the US is expected to decrease by 159,300. Demand for certain ob/gyn subspecialties is expected to increase as the US population ages. Fear of professional liability claims has caused some ob/gyns to stop performing certain procedures or leave practice. 46 women in ob/gyn leadership positions in US medical schools.12 In 2008, compared with women, 3.7 times more men held division/section chief positions, 3.7 times more men held associate chair/vice chair positions, and 6.9 times more men held departmental chair positions.12 Whether this is a function of the relative unavailability of part-time or less traditional employment opportunities for faculty members requires further study. Although the number of physicians working part time has increased, several studies demonstrate no difference in performance measures between part-time and full-time practitioners.13,14 ﬁ is is reassuring news, but from a long-term public health perspective, an increase in the number of part-time practitioners may negatively affect access to care and therefore requires tracking. Moreover, potential barriers to part-time practice include fixed professional liability premiums, medical student debt, incomparable beneTts packages, lower income, practice instability, and questionable future professional opportunities. If physicians do eliminate certain aspects of their practice for a time or stop practicing altogether, some may decide to return to clinical practice. ﬁe exact extent to which physician reentry will become an CONTEMPORARYOBGYN.NET JULY 2011 issue in the ob/gyn specialty is unknown. A recent study of 5,000 physicians listed as being “inactive” in the American Medical Association (AMA) Physician Masterfile revealed that 15% had reentered the workforce.15 Very few retraining programs exist; those that do require signiTcant travel and a substantial T nancial commitment.16 State licensing boards and hospital credentialing committees are beginning to look at the requirements for reentering physicians. In addition, ACOG and the AMA should continue to work to facilitate creation of programs throughout the country that include standardized mechanisms for evaluation and certification. Another issue of significant importance to physicians is work-life balance. Traditional gender roles may complicate this issue for women. Woodrow and colleagues noted, “Female physicians spend more than twice as much time as male physicians on family and household work, despite comparable professional hours.”17-19 This situation may have contributed to a recent special issue of Time magazine being devoted to “ﬁe State of the American Woman.” The following line is displayed on the cover: “A new poll shows that they [women] are more powerful—but less happy,” and one of the articles in this issue is titled, “Daily life is a story of diplomacy under stress.”20 It is interesting to note that employee assistance programs, mentoring, and education on available resources play important roles in helping physicians avoid burnout and improve their sense of well being. Data demonstrate that male and female ob/gyns experience similar degrees of satisfaction with their medical practices. 21 However, a cultural bias may be evolving against male ob/gyns in media portrayals. A recent study of 6 magazines geared toward female readers revealed that female ob/gyns were interviewed as physician experts 47% to 80% of the time. In 5 magazines, pronouns referring to physicians were changed from gender-neutral to female-specific. 22 Although one must acknowledge that historically women were WORKFORCE CHALLENGES not embraced as physicians by either the medical profession or the public, it is important to confront discrimination against men as the pendulum swings in the other direction. ﬁose in charge should aim at directing requests for media interviews that are conducted through medical and academic institutions to both male and female ob/gyns. Workforce pipeline considerations: medical education One cannot discuss potential workforce changes in this country without addressing the future number of ob/gyns and their training. Our profession must meet the service needs of the population. When determining the appropriate number of physicians needed to provide care, advances in the profession and demographic changes must be considered. The very definition of what the practice of ob/gyn entails has changed or evolved significantly over the past few decades. Since the advent of managed care several decades ago, a debate has persisted regarding whether ob/gyns should be considered primary care providers or specialists. The availability of uterine artery embolization, progesterone-releasing intrauterine devices, and endometrial ablation techniques has been associated with a signif icant decrease in the need for hysterectomies. Surveillance data reveal a 1.9% decrease per year in US hysterectomy rates from 1997 to 2005. 23 Some residents have graduated from accredited programs having performed as few as 12 vaginal hysterectomies. The impressive growth of laparoscopic hysterectomies also contributes to the use of fewer open abdominal procedures. 24 Robotic surgery, in which 1 surgeon often is the only person manipulating the instruments, is now part of nearly all training programs but may have a negative impact on the residency surgical experience. Although all of these minimally invasive techniques can have potentially significant benefits for patients, we cannot ignore the effect they are having on resi- dent training. In some institutions, the only patients undergoing total abdominal hysterectomies are those with significant operative risk factors, which limits the number of learning opportunities for junior residents to become proficient and to eventually handle more challenging cases, including cesarean hysterectomies. All of these challenges to education offer opportunities to reevaluate our current graduate medical education (GME) structure, which tends to overemphasize inpatient care, traditional didactic teaching, and off-ser vice time. The current system offers all residents the same experience regardless of their indiv idual practice or fellowship plans. Formal training in such aspects as patient safety, informatics, and practice management might be invaluable to them. Given the limitations of GME funding and the current work-hour restrictions, perhaps we should reevaluate the length and format of training in favor of a 2- or 3-year core experience for all residents, with more learner-driven focus the remainder of the time. Tools such as patient simulation and competencies are helpful but they cannot provide the depth of experience gained from surgical mentoring or reallife ambulatory care experiences. One obvious solution to the looming physician workforce shortage would be to increase the number of residency positions in ob/gyn. Although this seems to be a necessary step, several important aspects must be considered. For example, if the volume of surgical procedures being performed by graduating residents is already insufficient, the addition of more residents to the programs will serve to dilute further the surgical experience. On the other hand, the surgical volume of individual residents might increase if there were fewer residents, but having fewer residency slots in this country will only exacerbate the predicted future workforce shortage. Advocating for increased federal funding for GME is not likely to gain much political traction in this era of deficits and spending reductions. JULY 2011 POWER POINTS The number of female ob/gyns has grown except in leadership positions. More physicians work fewer hours or are reentering practice after leaving or retiring. A cultural bias against male ob/gyns may be developing. CONTEMPORARY OB/GYN 47 WORKFORCE CHALLENGES POWER POINTS Ob/gyn procedures being taught in graduate medical education (GME) are shifting. Current GME offers the same experience to everyone, regardless of their practice or fellowship plans. Both GME and the ob/gyn specialty will be forced to adapt by workforce trends and patient access. 48 Clearly, although many of these forces are contradictory, our profession must address all of them. If more physicians are practicing part time and surgical volume is decreasing, skills will be compromised. If more physicians are retiring early and the aging baby boomer generation requires additional care, access to that care will be compromised. If residents’ surgical experiences are limited by the number of work hours permitted and educational content continues to expand as our understanding of molecular biology and genetics evolves, graduates will not be fully equipped to practice all aspects of our specialty. Increasing the number of ob/g y n residency program slots to meet predicted physician shortages will further compromise surgical experience for trainees. Addressing evolving needs Of the myriad challenges confronting our specialty, workforce issues are the most compelling. If they are not addressed, liability pressures will continue to affect patient access to care if physicians are reluctant to practice obstetrics or if they retire prematurely from this aspect of practice. Physician burnout compounded by issues of increasing healthcare regulation and paperwork contributes to this potential crisis. 25 Thus, it is critically important for our specialty to undergo continuous workforce analyses. Ob/gyn was notably absent from the 21 specialties highlighted in the 2010 AAMC analysis titled, “Recent Studies and Reports on Physician Shortages in the US.”6 A better understanding of potential patient access issues could inf luence policy makers about the need for meaningful tort reform. Phy sic i a n-le d te a m s s t a f fe d w it h nonphysician practitioners may help to provide greater va lue in patient care. Certified nurse midwives and nurse practitioners can be instrumental in meeting burgeoning needs. Evidence has shown that collaborative ob/gyn practices improve outcomes. One study that compared 179 advanced-practice CONTEMPORARYOBGYN.NET JULY 2011 nurse-obstetrician collaborative practice patients with 181 university patients revealed “acceptable perinatal outcomes, as judged by low birth weight and prematurity.”26 According to the ﬁ ndings of another study that evaluated 10 separate collaborative-care ob/gyn practices using patient surveys: “ . . . patients in this survey were accepting of the concept of collaborative practice and felt that it oTered quicker appointments, more time with the provider, more health information, and more specific diet information than did physician-only practices.”27 Policy makers also should recognize the importance of GME financing to selectively increase the number of ob/gyn residency positions. A recent book by Williams, Satiani, and Ellison concludes that the surgical field with the most serious pending shortage of graduating residents is ob/gyn, with approximately 14,000 too few slots. 28 The authors estimate that the current annual cost to train each class is $312 million, and the estimated cost to train the total number of residents deemed necessary from a workforce perspective is $489 million. Although it would be money well spent, the political leverage to dramatically increase GME expenditures does not appear to exist at this time. Summary The needs and expectations of an evolving society are transforming the field of ob/ gyn. Challenges and potential solutions to current work force qua nda ries a re outlined (Table). Forces at work include t h e i nc re a s i n g nu m b e r of o b/g y n s approaching retirement age, the growing population of elderly women with greater hea lt hca re needs, cont inued liabi lit y pressures discouraging physicians from practicing obstetrics, increasing gender and generational issues that bring about changes in practice patterns, and the stagnant number of residency positions. These factors contribute to the perception of an impending shortage of ob/gyns that could lead to decreased access to care. WORKFORCE CHALLENGES TABLE. Challenges and potential solutions to impending workforce issues Challenges Potential solutions Number of retiring physicians Part-time liability insurance rates Part-time practice Flexible job opportunities Gender and generational work hour changes Laborists, collaborative practices Aging population Additional workforce studies Physician geographic maldistribution Student loan forgiveness, incentives Liability pressures are greater than limited practices Meaningful liability reform Inadequate GME positions Enhanced GME financing/ residency slots Abbreviation: GME, graduate medical education. Compelling evidence exists for workforce stud ies in women’s hea lt hca re, including the expanding roles of physician-led collaboratives with nonphysician practitioners. Aspects of ob/gyn workforce needs that merit consideration include physician burnout, par t-time practice, physician reentry into clinical practice, and gender bias. Our specialty faces many challenges in graduate and postgraduate education, including the growth of minimally invasive procedures, increased awareness of robotic surgery, and limited resident exposure to uncomplicated open abdominal surgeries. Strategies to improve education and enhance practice patterns should begin with an ongoing dialogue about our specialty’s critical role in enhancing women’s healthcare. DR TRACY is an assistant professor at Harvard Medical School and attending physician in the Vincent Obstetrics and Gynecology Department at Massachusetts General Hospital, Boston. DR RAYBURN is the Randolph V Seligman Professor and Chair, Department of Obstetrics and Gynecology, University of New Mexico, Albuquerque. Dr Tracy has no conflicts of interest, real or apparent, to disclose with regard to the content of this article. Dr Rayburn reports that he is a member of the faculty/advisory board of the American College of Obstetricians and Gynecologists. The authors would like to acknowledge Edward Salsberg, MPA, and Douglas W Laube, MD, MEd, for their assistance. REFERENCES 1. Association of American Medical Colleges (AAMC) Statement on the Physician Workforce—June 2006. https://www.aamc.org/download/55458/data/ workforceposition.pdf. Accessed June 10, 2011. 2. Association of American Medical Colleges (AAMC) Center for Workforce Studies. Results of the 2009 Medical School Enrollment Survey: Report to the Council of Deans. April 2010. https://www.aamc. org/download/124780/data/enrollment2010.pdf.pdf. Accessed June 10, 2011. 3. US Department of Health and Human Services. Health Resources and Services Administration. Bureau of Health Professions. The Physician Workforce: Projections and Research Into Current Issues Affecting Supply and Demand. December 2008. ftp://ftp.hrsa.gov/migrated/ bhpr/workforce/physicianworkforce.pdf. Accessed June 10, 2011. 4. Rayburn WF. The obstetrician-gynecologist workforce in the United States: Facts, figures, and implications 2011. Washington, DC: American Congress of Obstetricians and Gynecologists; 2011. 5. Cull WL, O’Connor KG, Olson LM. Part-time work among pediatricians expands. Pediatrics. 2010:125(1):152-157. 6. Association of American Medical Colleges (AAMC) Center for Workforce Studies. Recent Studies and Reports on Physician Shortages in the US. May 2011. https://www.aamc.org/download/100598/data/ recentworkforcestudiesnov09.pdf. Accessed June 10, 2011. 7. Dill MJ, Salsberg ES; Center for Workforce Studies. The Complexities of Physician Supply and Demand: Projections Through 2025. Washington, DC: Association of American Medical Colleges; 2008. 8. US Department of Health and Human Services. Health Resources and Services Administration. Health Professions. Shortage Designation: Health Professional Shortage Areas and Medically Underserved Areas/ Populations. http://bhpr.hrsa.gov/shortage/. Accessed June 10, 2011. 9. Morrill M, Lukacz ES, Lawrence JM, Nager CW, Contreras R, Luber KM. Seeking healthcare for pelvic floor disorders: a population-based study. Am J Obstet Gynecol. 2007:197(1):86.e1-86.e6. 10. Klagholz J, Strunk AL. Overview of the 2009 ACOG Survey on Professional Liability. http://www.acog.org/ departments/professionalLiability/2009PLSurveynation al.pdf. Accessed June 10, 2011. 11. Brotherton SE, Rockey PH, Etzel SI. US graduate medical education, 2004-2005: trends in primary care specialties. JAMA. 2005;294(9):1075-1082. 12. Association of American Medical Colleges (AAMC). Women in U.S. Academic Medicine: Statistics and Benchmarking Report. 2008–2009. https://www.aamc. org/download/179554/data/wimstatisticsreport2009. pdf. Accessed June 10, 2011. 13. Fairchild DG, McLoughlin KS, Gharib S, et al. Productivity, quality, and patient satisfaction: comparison of part-time and full-time primary care physicians. J Gen Intern Med. 2001;16(10):663-667. 14. Murray A, Safran DG, Rogers WH, Inui T, Chang JULY 2011 CONTEMPORARY OB/GYN 49 WORKFORCE CHALLENGES H, Montgomery JE. Part-time physicians: physician workload and patient-based assessments of primary care performance. Arch Fam Med. 2000;9(4):327-332. 15. American Medical Association and American Academy of Pediatrics. Physician reentry into the workforce conference. Issue Brief 2: Data on reentry physicians. http://www.aap.org/reentry/reentry _ issuebrief2_final.pdf. Accessed June 17, 2011. 16. American Medical Association Council on Medical Education 2008 report on physician reentry. http://www. ama-assn.org/ama1/pub/upload/nm/377/cmerpt_6a-08. pdf. Accessed June 10, 2011. 17. Woodrow SI, Gilmer-Hill H, Rutka JT. The neurosurgical workforce in North America: a critical review of gender issues. Neurosurgery. 2006;59(4):749755; discussion 755-758. 18. Cujec B, Oancia T, Bohm C, Johnson D. Career and parenting satisfaction among medical students, residents and physician teachers at a Canadian medical school. CMAJ. 2000;162(5):637-640. 19. Kao LS, Wilson EB, Anderson KD. Gender differences among spouses of surgeons. Am J Surg. 2005;189(4):435-440. 20. Time Magazine Special Report: The State of the American Woman. Time. October 26, 2009. http://www. time.com/time/covers/0,16641,20091026,00.html?artI d=20091026?contType=gallery?chn=covers. Accessed June 10, 2011. 21. Emmons SL, Nichols M, Schulkin J, James KE, Cain JM. The influence of physician gender on practice satisfaction among obstetrician gynecologists. Am J Obstet Gynecol. 2006;194(6):1728-1739. 22. Kincheloe LR. Gender bias against male obstetriciangynecologists in women’s magazines. Obstet Gynecol. 2004;104(5 pt 1):1089-1093. 23. Merrill RM. Hysterectomy surveillance in the United States, 1997 through 2005. Med Sci Monit. 2008; 14(1):CR24-CR31. 24. Jacoby VL, Autry A, Jacobson G, Domush R, Nakagawa S, Jacoby A. Nationwide use of laparoscopic hysterectomy compared with abdominal and vaginal approaches. Obstet Gynecol. 2009;114(5):1041-1048. 25. Merrit J, Hawkins J, Miller P. Will the Last Physician in America Please Turn Off the Lights? A Look at America’s Looming Doctor Shortage. Irving, Texas: MHA Group; 2004. 26. Mvula MM, Miller JM Jr. A comparative evaluation of collaborative prenatal care. Obstet Gynecol. 1998:91(2):169-173. 27. Hankins GDV, Shaw SB, Cruess DF, Lawrence HC III, Harris CD. Patient satisfaction with collaborative practice. Obstet Gynecol. 1996:88(6):1011-1015. 28. Williams TE Jr, Satiani B, Ellison EC. The Coming Shortage of Surgeons: Why They Are Disappearing and What That Means for Our Health. Santa Barbara, CA: Praeger/ABC-CLIO; 2009. BEGIN YOUR FREE SUBSCRIPTION TODAY . . . Translating Science into Sound Clinical Practice JANUARY 2011 ContemporaryOBGYN.net New techniques for treating SUI PAGE 28 Understanding CDC’s new strep B guidelines PAGE 6 VOLUME 56, NUMBER 1 Genes determine severe morning sickness sufferers PAGE 10 And start enjoying these beneﬁts: • Peer-reviewed, problem solving clinical articles • Practical, timely information from ⇒eld experts • Information on diagnosis, treatment, and practice management • Up-to-date clinical news and research • Regular departments include Newsline, Legally Speaking, and MFM Consult Are infants born under midwife care at higher risk for death? PAGE 14 “Contemporary OB/GYN is packed with critical, useful information that OB/GYNs can use to improve their practices, even save lives.” 50 CONTEMPORARYOBGYN.NET JULY 2011 ContemporaryOBGYN.net Translating Science into Sound Clinical Practice For Products & Services Advertising, contact: Bill Smith (800) 225-4569 ext. 2718, bsmith@advanstar.com CONTINUING MEDICAL EDUCATION MARKETPLACE MEDICAL EQUIPMENT & SUPPLIES Green Help fund a cure • Soft, durable padded vinyl • Free socks $24.99 • Free shipping a pair • Wholesale pricing • 5% for Breast Cancer Research Foundation Brown Mauve 770-679-0228 Boot-Style Stirrups Fit Ofﬁce Exam Tables Fits Tables By: A Must For Ofﬁce-Based Surgery Midmark® Ritter® Hamilton Brewer ATLANTA, GA • NOVEmbER 3-5, 2011 www.harveystirrups.com 585-455-8229 CONTRACEPTIVE TECHNOLOGY SEMINARS QUEST FOR EXCELLENCE Register Today! Email: info@cforums.com • Phone: (800) 377-7707 • www.ContemporaryForums.com MEDICAL EQUIPMENT & SUPPLIES Don’t settle for cold stirrups, when your patients can snuggle their feet in cozy www.furrups.com For PRODUCTS & SERVICES advertising, please contact: Bill Smith • 800.225.4569, ext. 2718 To see the latest Products & Services ads, visit http://products.modernmedicine.com JULY 2011 CONTEMPORARY OB/GYN 51 RECRUITMENT For Recruitment Advertising, contact: Jacqueline Moran (800) 225-4569 ext. 2762, jmoran@advanstar.com NATIONAL www.PhysicianRecruiting.com Many Lifestyle Practice Opportunities Available with Light Call Schedules or 4 Day Workweeks in Top Locations Nationwide: Metros, Suburbs, Coastal Locations and College Towns. Base Salaries of $250,000 and the Earning Potential of $400,000. State of the Art Labor and Delivery Rooms with DaVinci Robotics available. Explore your options at www.PhysicianRecruiting.com or www.facebook.com/physicianrecruiting. For Immediate Assistance Call (866) 528-2387 CALIFORNIA Northern California Gynecologic Oncologist Position CONNECTICUT MATERNAL FETAL MEDICINE CENTRAL CONNECTICUT Saint Francis Hospital and Medical Center in Hartford, Connecticut, has an exceptional opportunity for a BC/BE Maternal Fetal Medicine Specialist to join a dynamic and evolving group within a multi-specialty teaching hospital. Join three Maternal Fetal Medicine physicians in a department led by Dr. John Rodis, Chairman of the Department of Obstetrics and Gynecology. The Hospital and Medical Center performs 3,200 deliveries per year, and houses a 30-bed postpartum unit and 28-bed Level III NICU. The ideal candidate should have expertise in targeted ultrasound, amniocentesis, CVS, fetal echocardiography and medical complications of pregnancy. The successful candidate will have the opportunity to train residents and fellows in a fully accredited Obstetrics and Gynecology program and to contribute to clinical research endeavors. We offer a competitive salary commensurate with experience and an attractive benefits package. Excellent opportunity for a BC/BE Gynecologic Oncologist to join Gould Medical Group, a 270 member multispecialty group established in 1948. Located just one and a half hours east of San Francisco, Modesto offers easy access to vacation spots such as Lake Tahoe, Napa Valley, and Yosemite National Park as well as affordable housing, good schools, and great weather. We offer competitive compensation, an excellent benefits package, relocation allowance, and early partnership with no “buy in”. If you are an experienced Maternal Fetal Medicine physician interested in an excellent clinical and teaching opportunity in beautiful New England, please contact Christine Bourbeau, Physician Recruitment, at 855.894.5590, or email a letter of interest and CV to cbourbea@stfranciscare.org. Robotic assisted surgery 100% Gynecologic Oncology practice 20 referring Gould OB/GYN Physicians in 4 nearby locations Full call coverage, 4½ day work week Epic EMR PACS radiology services BC/BE GENERAL OB/GYN PHYSICIAN Contact Dr. C.V. Allen Phone: (866) 454-6853 Fax: (209) 550-4892 gmgrecruiting@sutterhealth.org www.suttergould.org/doctors To see the latest RECRUITMENT ads, visit us at http://Careers.ModernMedicine.com 52 ContemporaryObgyn.net JULY 2011 EEO/AA – M/F/D/V, pre-employment drug testing EASTERN CONNECTICUT Five-physician group with 3 nurse midwives seek a bc/be ob gyn physician to join our thriving private practice in historic Eastern Connecticut. We are affiliated with a progressive community hospital that see’s about 500 deliveries per year; with on-site interventional radiology, progressive obstetric care and full scale gyn and advanced minimally invasive surgeries. We perform hysteroscopy, ablation and BTL in our newly-renovated office. Located in a two university town that is a short drive from NYC, Boston and Providence, our community has affordable real estate, exceptional schools and many recreational & cultural activities. Enjoy reasonable call, fast partnership tract, and superb quality of life. Colleen Tighe ctighe@womenshealthusa.com 860-450-7227 RECRUITMENT FLORIDA IDAHO ORLANDO AREA Maternal Fetal Medicine 45 Minutes Frin ue Beaco! Level 3 hospital ~ No emergency room call Income potential unlimited Send CV to e-mail: colleenfitch@mac.com or fax: 407-209-3575 For more information, please call 407-418-9103 OB/GYN • Live and work in a great location • Family-oriented, safe city with all amenities • Flexible schedule including part-time • New 32-bed Level III NICU, OB unit, Boise, Idaho Seeking BC/BE OB/GYN physician and BC/BE URO/GYN physician to join 5 physician group Flexible Practice & Quality Lifestyle maternal transport team and collegial subspecialty • MFM back-up/consultation • Competitive compensation and benefits with exceptional performance-based bonuses ▪ 24/7 laborist model Contact: Sylvia Chariton at 800.309.5388 Email: sylvchar@sarmc.org or FAX: 208.367.7964 http://www.saintalphonsus.org/careers-video.html FLORIDA Family Health Centers of Southwest Florida, Inc. (FHC) is a private, not for profit, multispecialty, Federally Qualified Healthcare Center and has been Joint Commission accredited for 15 years. Headquartered in beautiful Ft. Myers, Florida , our community health center was established in the mid 1960’s. Please visit our website at www.fhcswf.org. KANSAS Fort Myers FHC is offering a great opportunity for an experienced BC OB/GYN; bilingual English-Spanish preferred. Our Women’s Health Team has privileges at the state-of-the-art facilities of Lee Memorial Health System Hospitals. A 3 On Call rotation consisting of ten 12 hour shifts per month, including weekends, behind 6 CNMs. Competitive Salary and Comprehensive Benefits Package including Malpractice Insurance. J-1 Eligible. Respond to Human Resources, P.O. Box 1357, Ft. Myers, FL 33902 or Fax (239) 278-3203; Email fhcopportunities@hcnetwork.org EOE/Drug Free For RECRUITMENT Advertising, Contact: JACQUELINE MORAN 440-891-2762 jmoran@advanstar.com SE Kansas College Community Join well established private practice in dynamic family oriented college community 45 minutes to Wichita and 90 minutes to Tulsa associated with a modern and financially stable hospital with up to date L/D Wing doing 300 annual deliveries. 1-3 call. Excellent salary, bonus, benefits and future partnership. OBGYN Search, 800-831-5475, Fax: 314-984-8246, obgynsrch@aol.com, www.obgynpractices.com MAINE SOUTHERN MAINE Excellent position in patient-centered OBGYN group practice. State-of-the-art medical center; level II nursery; midwives; Women’s Center; Excellent compensation and beneﬁts, 100% student loan reimbursement! $25,000 Sign on bonus, $10,000 moving expenses. Maine’s second largest city. Home of Bates College. 40mins from Portland, Jetport, and coast. Excellent public schools. Vibrant, diverse patient population. Contact: Susan Edson sedson@nehs.net 207-866-5680 www.HealthSearchNewEngland.com HTTP://CAREERS.MODERNMEDICINE.COM JULY 2011 CONTEMPORARY OB/GYN 53 RECRUITMENT MISSOURI NEW YORK St. Louis Area Hospital employed obgyn position in family oriented community 45 minutes to St. Louis suburbs associated with a ﬁnancially stable hospital with modern birthing unit doing 200 annual deliveries. 1-2 call. Excellent salary, bonus and beneﬁts. OBGYN Search, 800-831-5475, Fax: 314-984-8246, obgynsrch@aol.com, www.obgynpractices.com NEW JERSEY A well established growing practice is seeking a full-time OB/ GYN located in Bergen/Hudson county, NJ only minutes from NYC. It is affiliated with a medical center which was recently ranked 4th in the nation by Modern Healthcare Magazine for “Best Places to Work”. The Medical Center handles about 1500 deliveries per year, offers onsite Interventional Radiology, a NeoNatology unit and advanced surgical services including robotic procedures. Candidates must be board-certiﬁed in Obstetrics and Gynecology. Requires participation in group call schedule. Salary is commensurate with experience. Beneﬁts include malpractice, generous CME stipend, vacation, health/dental beneﬁts, 401K and proﬁts sharing after 1 year. Send inquiries to: Ray Dreyfuss 718 Teaneck Road, Teaneck, NJ 07666 Fax: 201-833-3043 NEW MEXICO Farmington, New Mexico Outstanding opportunity for BC/BE Ob-Gyn Physician to join an independent group of four. New facility, on-site Sonography and Pelvic Floor Therapy, Level I Nursery. Competitive salary, excellent beneﬁts, and relocation. Enjoy skiing, ﬁshing, hiking, golf, and many other outdoor adventures. Contact Terri Smith tsmith@sjrmc.net, phone (888)282-6591 www.sanjuanregional.com or www.sjrmcdocs.com NEW YORK Maternal-Fetal Medicine New York, Mid-Hudson Valley Openings for BC/BE Fellowship-trained Maternal-Fetal Medicine Specialist. Support over 20 general Ob/Gyn physicians within multi-specialty group medical practice. 65 miles from Manhattan. Opportunity for personal and professional growth in the fastest growing practice in New York State, located in one of the fastest growing regions in New York State! • State-of-the-art facility. • 10-bed Level II NICU located in all-new hospital birthing center. • Electronic medical records. In-house Digital imaging, including MR, CT and Ultrasound. • Excellent compensation/partnership track; outstanding opportunity in a unique and highly successful practice. Please Write, Fax or Email to: Hal Teitelbaum, MD, MBA, Managing Partner 155 Crystal Run Road, Middletown, NY 10941 Fax: 845. 703. 6201 Email: hteitelbaum@crystalrunhealthcare.com Physician Wanted - NYC Age-Management Clinic Established 1997 seeks Board Certified / Eligible Internist, Gynecologist or Endocrinologist P/T (16-24 hrs/wk) No On-Call Contact Alicia at 212.888.7074 jobs@PhysioAge.com www.PhysioAge.com http://careers.modernmedicine.com 54 ContemporaryObgyn.net JULY 2011 crystalrunhealthcare.com SW New York Hospital employed multispeciality group seeking Obgyn in dynamic family oriented community 90 minutes to New York City with offices in PA/NY associated with a ﬁnancially stable 189 bed hospital with up to date birthing unit doing 300 annual deliveries. 1-3 call. Excellent salary, bonus and beneﬁts. OBGYN Search, 800-831-5475, Fax: 314-984-8246, obgynsrch@aol.com, www.obgynpractices.com Recruitment Advertising Can Work For You! RECRUITMENT NEW YORK UTAH Hospital employed position joining two obgyn’s in family oriented Finger Lakes region 45 minutes to Rochester associated with a modern and financially stable 72 bed hospital with beautiful L/D Unit doing 300 annual deliveries. 1-3 call. Excellent salary, bonus and benefit package. OBGYN Search, 800-831-5475, Fax: 314-984-8246, obgynsrch@aol.com, www.obgynpractices.com Intermountain is frequently referenced nationally as one of the leaders in delivering high quality/low cost health care. Intermountain Healthcare needs one experienced BC OB/GYN in Heber, Utah. Send CV to Intermountain Healthcare, Physician Recruiting, 36 S. State St, 21 Fl, Salt Lake City, UT 84111. 800-888-3134. http://physicianjobsintermountain.org. Rochester Area OHIO NE Ohio Hospital employed obgyn position in dynamic family oriented community one hour to Cleveland and Pittsburgh associated with a modern and financially stable 120 bed hospital with beautiful L/D Wing doing 500-600 annual deliveries. 1-3 call going to 1-4. Excellent salary, bonus and benefits. OBGYN Search, 800-831-5475, Fax: 314-984-8246, obgynsrch@aol.com, www.obgynpractices.com Intermountain is frequently referenced nationally as one of the leaders in delivering high quality/low cost health care. Intermountain Healthcare needs one BC/BE gynecologist in Provo, Utah. Send CV to Intermountain Healthcare, Physician Recruiting, 36 S. State St, 21 Fl, Salt Lake City, UT 84111. 800-888-3134. http://physicianjobsintermountain.org WASHINGTON, D.C. PENNSYLVANIA Pittsburgh Area Two well established lucrative private practices in family oriented communities 45 minutes to downtown Pittsburgh seeking physician for partnership and future takeover of the practice in 259/209 Bed hospitals doing 500-1000 deliveries. 1-2/1-4 call schedules. $250K salary,production bonus and benefits. OBGYN Search, 800-831-5475, Fax: 314-984-8246, obgynsrch@aol.com, www.obgynpractices.com RECRUITMENT WEB PACKAGES Join one of the largest recruitment networks on the Internet with over 250 partner sites. Find The Best Healthcare Candidates. Call Today For Web Package Details! Jacqueline Moran Phone: 800.225.4569, ext. 2762 E-mail: jmoran@advanstar.com Ob/Gyn Generalist POsitiOn Georgetown University Hospital / MedStar Health in the Georgetown section of Washington, DC is seeking a Board Certiﬁed / Board Eligible Ob/Gyn physician for the Generalist Division. The position encompasses direct, full range of Ob/Gyn patient care and an academic title at Georgetown University Medical Center commensurate with experience and training. Medical student and resident teaching is expected. The hospital-based position involves a private practice setting on site at GUH, a full-service hospital with a Level III NICU and on-site MFM providers. The Division of General Gynecology and Obstetrics is seeking a personable and motivated provider with excellent clinical and surgical skills; experience with laparoscopic and vaginal surgery is desired. Call is one in 8-9 nights and only at GUH. Salary is competitive with incentive potential based on productivity after the ﬁrst year. Malpractice costs are covered through the department and beneﬁts are provided through MedStar Health. For more information, please contact Helain J. Landy, MD, Professor and Chair, Department of Ob/Gyn, c/o Robin Reath rar9@gunet.georgetown.edu or 202-444-8757 OB Opportunity in DC Join a highly respected and established private practice in Virginia seeking an experienced obstetrics and gynecology physician who wants to make a difference. The ideal candidate will need to be a team player that can build a strong leadership role with major healthcare facilities nearby. Exceptional salary with all benefits and paid malpractice. Plus enjoy the DC/Fairfax area with cultural activities and strong economy. Contact Natasha Bell at 800-586-5051 ex. 6682 or email Natasha.bell@comphealth.com Ref#21570. Visit Us Online: http://careers.modernmedicine.com JULY 2011 CONTEMPORARY OB/GYN 55 ADVERTISER INDEX AMERIFIT 11 Brainstrong Citracal Qd 23 One A Day Women’s Prenatal 39 COOPER SURGICAL Her Option 17 GENZYME CORPORATION Seprafilm GRACEWAY PHARMACEUTICALS Zyclara GYRUS ACMI Innovate 43 HOLOGIC Cervista HPV 13 KINETIC CONCEPTS Prevena Incision Management System 19 PACIFIC WORLD Bio-Oil PFIZER Premarin Inside front cover-2 ROCHE DIAGNOSTICS HPV Test 9 SCHERING PLOUGH NuvaRing Cover tip SHIONOGI PHARMA INC Prenate VERMILLION INC OVA1 27 YALE NEW-HAVEN HOSPITAL Leadership in Patient Safety 31 BAYER HEALTHCARE LLC FEATURED NEXT MONTH in 5, 6 Inside back cover, back cover 35B 32, 33 • Myofascial pain syndrome: An overlooked source of chronic pain • Addressing the challenges of ectopic pregnancy • MFM Consult: Evaluating and managing isolated echogenic bowel 56 CONTEMPORARYOBGYN.NET JULY 2011 [zi-clar-a] The frequency and severity of local skin reactions were similar in both genders, with the following exceptions: a) flaking/scaling occurred in 40% of men and in 26% of women and b) scabbing/crusting occurred in 34% of men and in 18% of women. In the clinical trials, 32% (126/400) of subjects who used ZYCLARA Cream and 2% (4/202) of subjects who used vehicle cream discontinued treatment temporarily (required rest periods) due to adverse local skin reactions, and 1% (3/400) of subjects who used ZYCLARA Cream discontinued treatment permanently due to local skin/application site reactions. INDICATIONS AND USAGE Other adverse reactions reported in subjects treated with ZYCLARA Cream include: rash, back pain, application site rash, application site cellulitis, application site excoriation, application site bleeding, scrotal pain, scrotal erythema, scrotal ulcer, scrotal edema, sinusitis, nausea, pyrexia, and influenza-like symptoms. External Genital Warts Postmarketing Experience BRIEF SUMMARY OF PRESCRIBING INFORMATION SEE PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION ZYCLARA Cream is indicated for the treatment of external genital and perianal warts (EGW)/condyloma acuminata in patients 12 years or older. Limitations of Use Treatment with ZYCLARA has not been studied for prevention or transmission of HPV. Unevaluated Populations The safety and efficacy of ZYCLARA Cream have not been established in the treatment of: D>;.=1;*527=;*?*027*5,.;?2,*5;.,=*58;27=;**7*51>6*79*925586*?2;*5-2<.*<. D*,=272,4.;*=8<2<@1.7=;.*=.-@2=168;.=1*787.,B,5.=;.*=6.7=,8>;<.27=1.<*6.*;.* D9*=2.7=<@2=1A.;8-.;6*9206.7=8<>6. D<>9.;ficial basal cell carcinoma. D266>78<>99;.<<.-9*=2.7=< The following adverse reactions have been identified during post-approval use of imiquimod. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Application Site Disorders: tingling at the application site. Body as a Whole: angioedema. Cardiovascular: capillary leak syndrome, cardiac failure, cardiomyopathy, pulmonary edema, arrhythmias (tachycardia, supraventricular tachycardia, atrial fibrillation, palpitations), chest pain, ischemia, myocardial infarction, syncope. Endocrine: thyroiditis. Gastro-Intestinal System Disorders: abdominal pain. CONTRAINDICATIONS None. Hematological: decreases in red cell, white cell and platelet counts (including idiopathic thrombocytopenic purpura), lymphoma. WARNINGS AND PRECAUTIONS Hepatic: abnormal liver function. Local Skin Reactions Infections and Infestations: herpes simplex. 7=.7<.58,*5<427;.*,=287<27,5>-270<427@..92708;.;8<287,*78,,>;*/=.;*/.@*9952,*=287<8/ ZYCLARA Cream and may require an interruption of dosing. ZYCLARA Cream has the potential to exacerbate inflammatory,87-2=287<8/=1.<42727,5>-270,1;872,0;*/=?.;<><18<=-2<.*<. Musculo-Skeletal System Disorders: arthralgia. -6272<=;*=2878/)(#;.*62<78=;.,866.7-.->7=25=1.<4272<1.*5.-/;86*7B9;.?28><-;>08; surgical treatment. Respiratory: dyspnea. Systemic Reactions 5>524.<207<*7-<B69=86<6*B*,,869*7B8;.?.79;.,.-.58,*5<427;.*,=287<*7-6*B27,5>-. /*=20>.7*><.*/.?.;6B*502*<*;=1;*502*<6*5*2<.*7-,1255<727=.;;>9=2878/-8<270*7-*<<.<<6.7= of the patient should be considered. Neuropsychiatric: agitation, cerebrovascular accident, convulsions (including febrile convulsions), depression, insomnia, multiple sclerosis aggravation, paresis, suicide. Urinary System Disorders: proteinuria, urinary retention, dysuria. Skin and Appendages: exfoliative dermatitis, erythema multiforme, hyperpigmentation, hypertrophic scar, hypopigmentation. Vascular: Henoch-Schonlein purpura syndrome. Ly691*-.789*=1B8,,>;;.-278/<>+3.,=<@2=1*,=272,4.;*=8<2<=;.*=.-@2=1)(#;.*6%12< ;.*,=287;.<85?.-27*55<>+3.,=<+B@..4<*/=.;,8695.=2878/=;.*=6.7=. USE IN SPECIFIC POPULATIONS Ultraviolet Light Exposure Risks There are no adequate and well-controlled studies in pregnant women. ZYCLARA Cream should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Exposure to sunlight (including sunlamps) should be avoided or minimized during use of ZYCLARA Cream. "*=2.7=<<18>5-+.@*;7.-=8><.9;8=.,=2?.,58=1270.0*1*=@1.7><270)(#;.*6"*=2.7=<@2=h sunburn should be advised not to use ZYCLARA Cream until fully recovered. Patients who may have ,87<2-.;*+5.<>7.A98<>;..0->.=8=1.2;8,,>9*=287*7-=18<.9*=2.7=<@2=1271.;.7=<.7<2=2?2=B=8 sunlight should exercise caution when using ZYCLARA Cream. 7*7*726*5918=8,*;cinogenicity study262:>268-,;.*6<18;=.7.-=1.=26.=8<427=>68;/8;6*=287 The enhancement of ultraviolet carcinogenicity is not necessarily dependent on phototoxic mechanisms. %1.;./8;.9*=2.7=<<18>5-627262C.8;*?82-7*=>;*58;*;=2/2,2*5<>75201=.A98<>;. Increased Risk of Adverse Reactions with Concomitant Imiquimod Use C87,862=*7=><.8/)(#*7-*7B8=1.;262:>268-9;8->,=<27=1.<*6.=;.*=6.7=*;.*<18>5-+. *?82-.-<27,.=1.B,87=*27=1.<*6.*,=2?.270;.-2.7=262:>268-*7-6*B27,;.*<.=1.;2<4/8;*7-<.?.;2=y 8/58,*5<427;.*,=287< The safety of concomitant use of ZYCLARA Cream and any other imiquimod products has not been established and should be avoided since they contain the same active ingredient (imiquimod) and may increase t1.;2<4/8;*7-<.?.;2=B8/<B<=.62,;.*,=287< Immune Cell Activation in Autoimmune Disease Z(#;.*6<18>5-+.><.-@2=1,*>=287279*=2.7=<@2=19;..A2<=270*>=8266>7.,87-2=287<+.,*><. imiquimod activates immune cells. ADVERSE REACTIONS Because clinical trials are conducted under widely varB270,87-2=287<*-?.;<.;.*,=287;*=.<8+<.;ved in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Clinical Trials Experience: External Genital Warts 7=@8-8>+5.+527-95*,.+8,87=;855.-<=>-2.< <>+3.,=<*9952.->9=887.9*,4.=8/)(#;.*6 8;?.12,5.-*25B/8;>9=8@..4< %1.68<=/;.:>.7=5B;.98;=.-*-?.;<.;.*,=287<@.;.*9952,*=287<2=.;.*,=287<*7-58,*5<427;.*,=287< Selected adverse reactions are listed in Table 1. Table 1: Selected Adverse Reactions Occurring in ≥2% of ZYCLARA Treated Subjects and at a Greater Frequency than with Vehicle in the Combined Trials (EGW) ZYCLARA Cream 3.75% Vehicle Cream Preferred Term (N=400) (N=202) Application site pain 28 (7%) 1 (<1%) Application site irritation 2 (1%) Application site pruritus 11 (3%) 2 (1%) Vaginitis bacterial* 2 (2%) Headache 1 (<1%) *Per,.7=*0.+*<.-87/.6*5.989>5*=2878//8;)(#;.*6*7- /8;?.12,5.,;.*6 8,*5<427;.*,=287<@.;.;.,8;-.-*<*-?.;<.;.*,=287<875B2/=1.B.A=.7-.-+.B87-=1.=;.*=6.7=*;.* if they required any medical intervention, or they resulted in patient discontinuation from the study. The incidence and severity of selected local skin reactions are shown in Table 2. Table 2: Selected Local Skin Reactions in the Treatment Area Assessed by the Investigator (EGW) All grades*, (%) ZYCLARA Cream 3.75% Vehicle Cream Severe, (%) (N=400) (N=202) Erythema* 70% 27% Severe erythema 9% <1% Edema* 41% 8% Severe edema 2% 0% Erosion/ulceration* 36% 4% Severe erosion/ulceration 11% <1% Exudate* 34% 2% Severe exudate 2% 0% *Mild, Moderate, or Severe Pregnancy Pregnancy Category C: The animal multiples of human exposure calculations were based on daily dose comparisons for the reproductive toxicology studies described in this label. The animal multiples of human exposure were based on weekly dose comparisons for the carcinogenicity studies described in this label. For the animal multiple of human exposure ratios presented in this label, the Maximum Recommended Human Dose (MRHD) was set at 2 packets (500 mg cream) per treatment of actinic keratosis with ZYCLARA Cream (imiquimod 3.75%, 18.75 mg imiquimod) for BSA comparison. The maximum human AUC value obtained in the treatment of external genital and perianal warts was higher than that obtained in the treatment of actinic keratosis and was used in the calculation of animal multiples of MRHD that were based on AUC comparison. Systemic embryofetal development studies were conducted in rats and rabbits. Oral doses of 1, 5 and 20 mg/kg/day imiquimod were administered during the period of organogenesis (gestational days 6 – 15) to pregnant female rats. In the presence of maternal toxicity, fetal effects noted at 20 mg/kg/day (163X MRHD based on AUC comparisons) included increased resorptions, decreased fetal body weights, delays in skeletal ossification, bent limb bones, and two fetuses in one litter (2 of 1567 fetuses) demonstrated exencephaly, protruding tongues and low-set ears. No treatment related effects on embryofetal toxicity or teratogenicity were noted at 5 mg/kg/day (28X MRHD based on AUC comparisons). Intravenous doses of 0.5, 1 and 2 mg/kg/day imiquimod were administered during the period of organogenesis (gestational days 6 – 18) to pregnant female rabbits. No treatment related effects on embryofetal toxicity or teratogenicity were noted at 2 mg/kg/day (2.1X MRHD based on BSA comparisons), the highest dose evaluated in this study, or 1 mg/kg/day (115X MRHD based on AUC comparisons). A combined fertility and peri- and post-natal development study was conducted in rats. Oral doses of 1, 1.5, 3 and 6 mg/kg/day imiquimod were administered to male rats from 70 days prior to mating through the mating period and to female rats from 14 days prior to mating through parturition and lactation. No effects on growth, fertility, reproduction or post-natal development were noted at doses up to 6 mg/kg/day (25X MRHD based on AUC comparisons), the highest dose evaluated in this study. In the absence of maternal toxicity, bent limb bones were noted in the F1 fetuses at a dose of 6 mg/kg/day (25X MRHD based on AUC comparisons). This fetal effect was also noted in the oral rat embryofetal development study conducted with imiquimod. No treatment related effects on teratogenicity were noted at 3 mg/kg/day (12X MRHD based on AUC comparisons). Nursing Mothers It is not known whether imiquimod is excreted in human milk following use of ZYCLARA Cream. Because many drugs are excreted in human milk, caution should be exercised when ZYCLARA Cream is administered to nursing women. Pediatric Use Safety and efficacy in patients with external genital/perianal warts below the age of 12 years have not been established. Geriatric Use Clinical studies of ZYCLARA Cream for EGW did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Of the 400 subjects treated with ZYCLARA Cream in the EGW clinical studies, 5 subjects (1%) were 65 years or older. OVERDOSAGE Topical overdosing of ZYCLARA Cream could result in an increased incidence of severe local skin reactions and may increase the risk for systemic reactions. Hypotension was reported in a clinical trial following multiple oral imiquimod doses of >200 mg (equivalent to ingestion of the imiquimod content of more than 21 packets of ZYCLARA). The hypotension resolved following oral or intravenous fluid administration. Rx Only Manufactured by 3M Health Care Limited Loughborough LE11 1EP England Distributed by Graceway Pharmaceuticals, LLC Bristol, TN 37620 Issued: March 2011 ZYC031137 What patients want in the treatment of external genital warts (EGW)... Effectively clears genital warts and keeps patients clear Short treatment, daily dosing s Applied once daily for up to 8 weeks Signiﬁcant clearance in females s 37% complete clearance, 48% partial clearance _75% reduction in – Partial clearance deﬁned as > EGW count from baseline Patients who clear with Zyclara can expect to remain clear s Only 15% of patients had a recurrence at 12 weeks posttreatment1 Tough on warts, easy on patients s Low incidence of treatment-related adverse events at the application site: itching (3%), irritation (6%), or pain (7%)1 s Local skin reactions, most of which were mild to moderate, included severe erythema (9%) and severe erosion/ulceration (11%)1 Zyclara Cream is indicated for the treatment of external genital and perianal warts/condyloma acuminata in patients 12 years or older. In clinical studies, the most frequently reported adverse reactions were local skin and application site reactions. These reactions included erythema, edema, erosion or ulceration, and exudate at the genital wart site. Most local skin reactions were rated as mild to moderate. Intense local inﬂammatory reactions and/or ﬂu-like systemic signs and symptoms can occur. Dosing interruptions may be required. Avoid concomitant use of Zyclara Cream and any other imiquimod cream because of increased risk for adverse reactions. Zyclara Cream is not recommended for the treatment of urethral, intra-vaginal, cervical, rectal, or intra-anal human papilloma viral disease as it has not been studied. The effect of Zyclara Cream on the transmission of genital warts is unknown. Zyclara Cream may weaken condoms and diaphragms. Sexual contact should be avoided while the cream is on the skin. Please see Brief Summary of Prescribing Information on adjacent page. Reference: 1. Data on ﬁle. Graceway Pharmaceuticals, LLC. ©2011 Graceway Pharmaceuticals, LLC, Bristol, TN www.gracewaypharma.com ZYC1110186 www.ZyclaraCream.com 1