Publications (19)74.13 Total impact
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Article: An international response to questions about terminologies, investigation, and management of abnormal uterine bleeding: use of an electronic audience response system.
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ABSTRACT: More than 600 registrants attended a two-hour interactive symposium on abnormal uterine bleeding (AUB) at the Federation of Gynecology and Obstetrics World Congress in Cape Town, October 2009. Nearly 250 of these participants answered multiple questions through an electronic audience responder system. The audience heard five structured presentations on clinically important and controversial aspects of AUB, including terminologies and definitions, classification of causes, mechanisms of AUB in the absence of structural lesions of the reproductive tract, the potential for a structured menstrual history, and management of heavy menstrual bleeding (HMB) in low-resource settings. Numerous demographic details were collected, and a total of 30 questions to the audience were interspersed through each of the presentations. The audience demonstrated great variation in the way the terms AUB, menorrhagia, and dysfunctional uterine bleeding (DUB) are used, and considerable majorities agreed that the terms menorrhagia and DUB should be abolished. AUB should be the overarching term to describe all symptomatic departures from normal menstruation or the menstrual cycle. HMB is a suitable replacement term for menorrhagia. DUB can be replaced by the three clinical entities comprising "nonstructural" causes of AUB. There was a high consistency across demographic subgroups in answers to most questions. Acute and chronic AUB were defined, and aspects of a classification system for causes of AUB and of a structured menstrual history were explored. Issues related to investigation and hormonal treatment of HMB in low-resource settings were explored by registrants from developing countries.Seminars in Reproductive Medicine 09/2011; 29(5):436-45. · 3.80 Impact Factor -
Article: A five-year international review process concerning terminologies, definitions, and related issues around abnormal uterine bleeding.
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ABSTRACT: Over the past decade there has been an increasing realization about the extent of confusion associated with the many terminologies used to describe abnormal uterine bleeding (AUB). This led to the organization of an international workshop of 35 experts from 15 countries in Washington, D.C., USA, in 2005, which addressed the confusions and controversies around AUB. The workshop comprehensively addressed anomalies in the terminologies, definitions, and causes of AUB. It also began to address broader issues including investigations, quality of life, the need for structured symptom questionnaires, cultural aspects, and future research needs. This workshop led to a series of recommendations and publications and to the establishment of the International Federation of Gynecology and Obstetrics (FIGO) Menstrual Disorders Working Group. Since then, a series of international presentations and small group workshops has resulted in a wide awareness of the program and a comprehensive series of recommendations and publications. A particularly influential large-scale interactive workshop with 600 attendees was held during the 2009 FIGO World Congress, which demonstrated the broad acceptability of the current recommendations. This article describes the process leading to the development of international recommendations on terminologies, definitions, and classification of causes of AUB and the establishment of the FIGO Menstrual Disorders Working Group.Seminars in Reproductive Medicine 09/2011; 29(5):377-82. · 3.80 Impact Factor -
Article: The FIGO recommendations on terminologies and definitions for normal and abnormal uterine bleeding.
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ABSTRACT: Over the past 5 years there has been a major international discussion aimed at reaching agreement on the use of well-defined terminologies to describe the normal limits and range of abnormalities related to patterns of uterine bleeding. This article builds on concepts previously presented, which include the abandonment of long-used, ill-defined, and confusing English-language terms of Latin and Greek origin, such as menorrhagia and metrorrhagia. The term DYSFUNCTIONAL UTERINE BLEEDING should also be discarded. Alternative terms and concepts have been proposed and defined. The terminologies and definitions described here have been comprehensively reviewed and have received wide acceptance as a basis both for routine clinical practice and for comparative research studies. It is anticipated that these terminologies and definitions will be reviewed again on a regular basis through the International Federation of Gynecology and Obstetrics Menstrual Disorders Working Group.Seminars in Reproductive Medicine 09/2011; 29(5):383-90. · 3.80 Impact Factor -
Article: Physician survey of the effect of the 21-gene recurrence score assay results on treatment recommendations for patients with lymph node-positive, estrogen receptor-positive breast cancer.
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ABSTRACT: To survey the effect of the 21-gene recurrence score (RS) assay results on adjuvant treatment recommendations for patients with lymph node-positive (N+), estrogen receptor-positive (ER+) breast cancer. Medical oncologists who ordered the 21-gene RS assay were invited to complete a survey regarding their most recent patient with N+/ER+ breast cancer. We obtained responses from 160 (16%) of the 1,017 medical oncologists. Most of the respondents were in community (71%) versus academic (25%) settings and had practiced for a median of 11 years. T1, T2, or T3 disease was reported in 62%, 35%, and 3% of patients, respectively. One, two, three, or ≥ 4 nodes were reported in 69%, 18%, 6%, and 3% of patients, respectively. Eighty-six percent of the oncologists made treatment recommendations before obtaining the RS; 51% changed their recommendations after receiving the RS. In 33%, treatment intensity decreased from chemotherapy plus hormonal therapy to hormonal therapy alone. In 9%, treatment intensity increased from hormonal therapy alone to chemotherapy plus hormonal therapy. In 8%, treatment recommendations changed in a way that did not fit the definition of either increased or decreased intensity. In this survey of physician practice, the RS result was used to guide adjuvant treatment decision making in N+/ER+ breast cancer more often in patients with tumors less than 5 cm in size and one to three positive lymph nodes than in patients with larger tumors and four or more positive nodes and yielded an overall reduction in recommendations for chemotherapy.Journal of Oncology Practice 03/2011; 7(2):94-9. -
Article: Ovarian conservation at the time of hysterectomy and long-term health outcomes in the nurses' health study.
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ABSTRACT: To report long-term health outcomes and mortality after oophorectomy or ovarian conservation. We conducted a prospective, observational study of 29,380 women participants of the Nurses' Health Study who had a hysterectomy for benign disease; 16,345 (55.6%) had hysterectomy with bilateral oophorectomy, and 13,035 (44.4%) had hysterectomy with ovarian conservation. We evaluated incident events or death due to coronary heart disease (CHD), stroke, breast cancer, ovarian cancer, lung cancer, colorectal cancer, total cancers, hip fracture, pulmonary embolus, and death from all causes. Over 24 years of follow-up, for women with hysterectomy and bilateral oophorectomy compared with ovarian conservation, the multivariable hazard ratios (HRs) were 1.12 (95% confidence interval [CI] 1.03-1.21) for total mortality, 1.17 (95% CI 1.02-1.35) for fatal plus nonfatal CHD, and 1.14 (95% CI 0.98-1.33) for stroke. Although the risks of breast (HR 0.75, 95% CI 0.68-0.84), ovarian (HR 0.04, 95% CI 0.01-0.09, number needed to treat=220), and total cancers (HR 0.90, 95% CI 0.84-0.96) decreased after oophorectomy, lung cancer incidence (HR=1.26, 95% CI 1.02-1.56, number needed to harm=190), and total cancer mortality (HR=1.17, 95% CI 1.04-1.32) increased. For those never having used estrogen therapy, bilateral oophorectomy before age 50 years was associated with an increased risk of all-cause mortality, CHD, and stroke. With an approximate 35-year life span after surgery, one additional death would be expected for every nine oophorectomies performed. Compared with ovarian conservation, bilateral oophorectomy at the time of hysterectomy for benign disease is associated with a decreased risk of breast and ovarian cancer but an increased risk of all-cause mortality, fatal and nonfatal coronary heart disease, and lung cancer. In no analysis or age group was oophorectomy associated with increased survival.Obstetrics and Gynecology 06/2009; 113(5):1027-37. · 4.73 Impact Factor -
Article: Cost and utilization of COPD and asthma among insured adults in the US.
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ABSTRACT: This study evaluates the burden of concomitant chronic obstructive pulmonary disease (COPD) + asthma, two highly prevalent and costly conditions. The authors identified commercial enrollees from a large health plan database who were aged > or =40 years with medical and pharmacy benefits and medical claims with diagnosis codes for COPD or asthma between January 1, 2004 and December 31, 2004. We assigned patients to COPD or COPD + asthma cohorts, excluding all others. A patient index date was the first evidence date of COPD or COPD + asthma. We excluded those with one outpatient COPD or asthma claim or who were not continuously enrolled during the 12 months before and after index date. After controlling for differences, postindex respiratory-related emergency department (ED) visits and/or hospitalizations and costs were compared between cohorts. We identified 24,935 patients, 17,394 (70%) in the COPD cohort and 7,541 (30%) in the COPD + asthma cohort. COPD + asthma patients were younger (58 versus 60 years; p < 0.0001) and more were females (62% vs 45%; p < 0.0001). COPD + asthma patients were 1.6 times more likely to have respiratory-related EDs and/or hospitalizations than COPD patients (95% CI 1.5, 1.8), and had $1987 (SE = $174, p < 0.0001) more respiratory-related healthcare costs. Mean adjusted respiratory-related healthcare costs were $3803 for COPD and $5790 for COPD + asthma. Limitations include a potential for misclassification due to misdiagnosis or coding errors as well as traditional biases of observational studies including the potential for omitted variable bias. COPD + asthma patients are more costly and use more services than those with COPD, and may be more unstable and require more intensive treatment.Current Medical Research and Opinion 05/2009; 25(6):1385-92. · 2.38 Impact Factor -
Article: Asthma quality-of-care measures using administrative data: identifying the optimal denominator.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 03/2009; 102(2):98-102. · 2.83 Impact Factor -
Article: Clinical outcomes and resource utilization associated with laparoscopic and open colectomy using a large national database.
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ABSTRACT: To clarify national clinical and economic laparoscopic colectomy outcomes, we conducted a study of patients who underwent colectomy by laparoscopic or open approaches. Laparoscopy is becoming the preferred approach for colectomy in benign and malignant diseases. Although it is associated with significant clinical benefits, economic outcomes have varied. We analyzed cohorts of patient-level data from Premier Inc.'s Perspective Rx Comparative Database, which collects data from more than 500 hospitals throughout the United States. By reviewing hospital charge data, patients who underwent elective colectomies from July 1, 2004, through June 30, 2006, were identified using International Classification of Diseases, 9th Revision, Clinical Modification procedure codes. The colectomy had to be listed as the primary or secondary procedure of the hospitalization. Primary outcomes included transfusion rates, in-hospital complications, readmissions within 30 days, reoperations, length of stay, total hospitalization costs, and discharge dispositions and services. We identified 32,733 patients who had elective colectomies throughout 402 hospitals; 11,044 (33.7%) were laparoscopic and 21,689 (66.3%) were open colectomies. The mean age was 64.2 +/- 13.9 years and 53.8% were women. Laparoscopic colectomy patients had a longer mean operative time (195 +/- 76 vs. 178 +/- 80 minutes; P < 0.0001) and higher total hospital costs ($8076 vs. $7678; P = 0.0002). Laparoscopic patients had shorter mean length of stay (7.0 vs. 8.1; P < 0.0001) and fewer mean intensive care unit days (0.7 +/- 3.8 vs. 1.3 +/- 5.2 days; P < 0.0001). The laparoscopic cohort also had lower rates of transfusions (odds ratio [OR] = 0.68; P < 0.0001), in-hospital complications (OR = 0.89; P < 0.0001), and readmissions within 30 days (OR = 0.89; P = 0.0051), although reoperation rates were slightly, but significantly increased (OR = 1.78; P = 0.002). Laparoscopic colectomy patients were more likely to be discharged home without nursing care (OR = 0.70; P < 0.0001). Evaluation of a national administrative data set showed that patients who underwent laparoscopic colectomy had shorter intensive care unit and total hospital stays, fewer complications, lower mortality, fewer readmissions, and less use of skilled nursing facilities after discharge. There was a small but significant increase in reoperation rates and in-hospital costs with laparoscopic colectomy. Improved application of enhanced recovery programs and operative efficiencies may further improve resource utilization associated with laparoscopic colectomy.Annals of surgery 05/2008; 247(5):819-24. · 7.90 Impact Factor -
Article: A process designed to lead to international agreement on terminologies and definitions used to describe abnormalities of menstrual bleeding.
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ABSTRACT: There is considerable worldwide confusion in the use of terminologies and definitions around the symptom of abnormal uterine bleeding, and these are leading increasingly to difficulties in setting up multinational clinical trials and in interpreting the results of studies undertaken in single centers. To develop an agreement process through an international initiative to recommend clear, simple terminologies and definitions that have the potential for wide acceptance. After widespread consultation with relevant international and national organizations, journal editors, and individuals, a modified Delphi process was developed to assess current use of terminologies, followed by a structured face-to-face meeting of 35 clinicians (mostly gynecologists) and scientists in Washington, DC. Focused small-group discussions led to plenary assessment of concepts and recommendations by using an electronic keypad voting system. An international group of experts on disorders of menstruation. Women with complaint of menstrual symptoms. An international debate and consultation process. Expert debate and anonymous voting on agreement through use of electronic keypads. There was almost-universal agreement that poorly defined terms of classical origin that are used in differing ways in the English medical language should be discarded and that these should be replaced by simple, descriptive terms with clear definitions that have the potential to be understood by health professionals and patients alike and that can be translated into most languages. The major recommendations were to replace terms such as menorrhagia, metrorrhagia, hypermenorrhea, and dysfunctional uterine bleeding. Suggestions for potentially suitable replacement terms and definitions are made. A simple terminology has been recommended for the description and definition of symptoms and signs of abnormal uterine bleeding. This article should be a living document and should be part of an ongoing process with international medical and community debate. Classification of causes, investigations, and cultural and quality-of-life issues should be part of the ongoing process.Fertility and sterility 04/2007; 87(3):466-76. · 3.97 Impact Factor -
Article: Tumor necrosis factor antagonists: different kinetics and/or mechanisms of action may explain differences in the risk for developing granulomatous infection.
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ABSTRACT: Tumor necrosis factor (TNF) antagonists fall into 2 classes:etanercept (ETA) is a soluble TNF receptor, while infliximab (INF) and adalimumab (ADA) are monoclonal antibodies against TNF. All 3 drugs are effective in treating rheumatoid arthritis. However, these agents have been associated with an increased risk of granulomatous infections, such as tuberculosis and histoplasmosis. Several reports indicate that the incidence of granulomatous infections may potentially be higher in individuals treated with INF than ETA. We conducted a comprehensive literature search (1966 to 2004) to review the role of TNF in normal and disease states, and the mechanisms of action of the TNF inhibitors. Specifically, we searched for possible mechanisms for the apparent increase in granulomatous infections associated with TNF inhibitors and for reasons that there may be differences between them. Infection may result from a number of differences between ETA and INF or ADA. First, binding avidities are different, with ETA binding in a 1:1 ratio and INF/ADA binding in 2 to 3:1 ratios. Second, the clearances of ADA, ETA, and INF are different, being about 13 times higher for ETA than INF or ADA, thus resulting in higher steady-state drug levels for ADA and INF. Also, the methods of administration are different, intravenously (for INF) versus subcutaneously (for ETA and ADA), which results in lower peak concentrations for ETA and ADA, potentially explaining some of the differences in effects on granuloma formation. Third, INF and ADA have somewhat different mechanisms of action from ETA: INF and ADA are associated with antibody-mediated cell lysis, while ETA is not; INF may induce apoptosis in some tissues (eg, gastrointestinal [GI] mucosa) while ETA does not--although this is controversial and may not be true at steady state in synovium, where both drugs seem to cause apoptosis; ETA binds lymphotoxin-alpha while INF does not (ETA may thus be more efficient at preventing granuloma formation by this mechanism than INF); finally, ADA and INF seem to inhibit IFN-gamma expression (probably indirectly), while ETA does not. There are significant differences between the 2 classes of TNF antagonists in terms of both their kinetics and mechanisms of action. These differences may help explain the apparent differences in the incidence of granuloma-dependent infections among them.Seminars in Arthritis and Rheumatism 01/2007; 36(3):159-67. · 4.97 Impact Factor -
Article: Treatment strategies for skeletal complications of cancer.
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ABSTRACT: Skeletal complications are a common result of many cancers, particularly of multiple myeloma and bone metastases of solid tumors originating in the breast, prostate or lung. A number of treatment options are available, including radiotherapy, radiopharmaceuticals, surgery and chemotherapy. Recently, bisphosphonates have emerged as a promising new treatment option for bone complications of cancer. These agents are potent inhibitors of osteoclast activity that bind to the bone matrix, are released during bone resorption, and are subsequently internalized by osteoclasts, where they interfere with biochemical pathways and induce osteoclast apoptosis. Bisphosphonates also antagonize osteoclastogenesis and promote the differentiation of osteoblasts. As a result, bisphosphonates inhibit tumor-induced osteolysis and reduce skeletal morbidity. Bisphosphonates are generally well tolerated, although they have recently been associated with osteonecrosis of the jaw, a painful and debilitating side effect that is only beginning to be understood. Despite this concern, bisphosphonates are an important tool in the management of skeletal complications of cancer, providing benefits for the treatment of hypercalcemia, osteolytic lesions and fractures, as well as offering amelioration of pain and improvement in quality of life.Cancer biology & therapy 10/2006; 5(9):1074-7. · 2.64 Impact Factor -
Article: Managing bone complications of solid tumors.
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ABSTRACT: Bone metastases are a common occurrence in patients with breast cancer, lung cancer and prostate cancer. Bone metastases cause considerable morbidity including pain, impaired mobility, pathologic fracture, spinal cord or nerve root compression, bone marrow infiltration and hypercalcemia of malignancy. These complications result from the derangement of normal bone metabolism that arise from interactions between factors originating in tumor cells and others originating in the microenvironment of the bone. Fortunately, there is an increasing array of treatment options for the skeletal complications associated with bone metastases arising from breast, lung, and prostate cancer. The goals of treatment for such skeletal complications are to relieve pain and reduce the risk of fracture. Traditional therapies to treat skeletal malignancies include radiation, surgery, and chemotherapy. In recent years, bisphosphonates have become the treatment of choice because of their ability to reduce bone resorption, leading to decreases in hypercalcemia, new osteolytic lesions, and fractures, thereby ameliorating pain and improving quality of life.Cancer biology & therapy 10/2006; 5(9):1086-9. · 2.64 Impact Factor -
Article: Bone complications in multiple myeloma.
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ABSTRACT: Multiple myeloma is the malignant proliferation of plasma cells involving more than 10% of the bone marrow. The bone complications associated with multiple myeloma include bone pain, pathologic fractures, hypercalcemia of malignancy and cord compressions. The principal pathophysiology of bone disease in multiple myeloma is a shift in the balance of bone remodeling toward bone resorption. In recent years, bisphosphonates have become an important treatment for the bone complications of multiple myeloma. Potent inhibitors of osteoclast activity, bisphosphonates interfere with biochemical pathways and induce osteoclast apoptosis. Bisphosphonates also antagonize osteoclastogenesis and promote differentiation of osteoblasts, as well as inhibiting other aspects of osteoclast homeostasis and metabolism. Several studies have evaluated treatment with bisphosphonates in patients with multiple myeloma, and have demonstrated the efficacy of clodronate (Bonefos; Anthra Pharmaceuticals; Princeton, NJ; www.bonefos.com), pamidronate (Aredia; Novartis Pharmaceuticals Corp; East Hanover, NJ; www.pamidronate.com) and zoledronic acid (Zometa; Novartis Pharmaceuticals Corp; East Hanover, NJ; www.us.zometa.com) in reduction of pain, reduction of SREs and survival. Moreover, recent data suggest direct and indirect antimyeloma activity of pamidronate and zoledronic acid.Cancer biology & therapy 10/2006; 5(9):1082-5. · 2.64 Impact Factor -
Article: Pathophysiology of bone metastases.
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ABSTRACT: Normal bone remodeling maintains an appropriate balance between the action of osteoclasts (bone-resorbing cells) and osteoblasts (bone-forming cells). Skeletal malignancies, including bone metastases, disrupt the OPG-RANKL-RANK signal transduction pathway and promote enhanced osteoclast formation, thereby accelerating bone resorption and inducing bone loss. This osteolysis in turn leads to the release of bone-derived growth factors, contributing to a "vicious cycle" in which interactions between tumor cells and osteoclasts not only lead to increased osteoclastogenesis and osteolytic activity, but also aggressive growth and behavior of the tumor cells. The osteolytic complications associated with bone metastases are caused by tumor-induced alterations of the OPG-RANKL-RANK system, which are accompanied by enhanced bone resorption and disassociated from counterbalancing bone formation by osteoblasts.Cancer biology & therapy 10/2006; 5(9):1078-81. · 2.64 Impact Factor -
Article: Reactivation of latent granulomatous infections by infliximab.
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ABSTRACT: Although infliximab and etanercept share tumor necrosis factor (TNF) as a common therapeutic target, accumulating data indicate that infliximab (an anti-TNF monoclonal antibody) poses a greater risk of reactivation of latent granulomatous infections than does etanercept (a soluble TNF receptor). Similarly, infliximab is effective for the treatment of chronic granulomatous inflammatory conditions (e.g., Crohn disease) for which etanercept is ineffective. The ability of infliximab to disrupt established granulomas may be distinct from its ability to neutralize soluble TNF. Further research to elucidate the mechanism of the antigranuloma activity of infliximab is warranted.Clinical Infectious Diseases 09/2005; 41 Suppl 3:S194-8. · 9.15 Impact Factor -
Article: Does the collaborative model improve care for chronic heart failure?
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ABSTRACT: Organizationally based, disease-targeted collaborative quality improvement efforts are widely applied but have not been subject to rigorous evaluation. We evaluated the effects of the Institute of Healthcare Improvement's Breakthrough Series (IHI BTS) on quality of care for chronic heart failure (CHF). We conducted a quasi-experiment in 4 organizations participating in the IHI BTS for CHF in 1999-2000 and 4 comparable control organizations. We reviewed a total of 489 medical records obtained from the sites and used a computerized data collection tool to measure performance on 23 predefined quality indicators. We then compared differences in indicator performance between the baseline and post-intervention periods for participating and non-participating organizations. Participating and control patients did not differ significantly with regard to measured clinical factors at baseline. After adjusting for age, gender, number of chronic conditions, and clustering by site, participating sites showed greater improvement than control sites for 11 of the 21 indicators, including use of lipid-lowering and angiotensin converting enzyme inhibition therapy. When all indicators were combined into a single overall process score, participating sites improved more than controls (17% versus 1%, P < 0.0001). The improvement was greatest for measures of education and counseling (24% versus -1%, P < 0.0001). Organizational participation in a common disease-targeted collaborative provider interaction improved a wide range of processes of care for CHF, including both medical therapeutics and education and counseling. Our data support the use of programs like the IHI BTS in improving the processes of care for patients with chronic diseases.Medical Care 08/2005; 43(7):667-75. · 3.41 Impact Factor -
Article: Mechanisms of differential immunogenicity of tumor necrosis factor inhibitors.
Current Rheumatology Reports 04/2005; 7(1):3-9. -
Article: Granulomatous infections due to tumor necrosis factor blockade: correction.
Clinical Infectious Diseases 11/2004; 39(8):1254-5. · 9.15 Impact Factor -
Article: Mechanisms of action of tumor necrosis factor antagonist and granulomatous infections.
The Journal of Rheumatology 11/2004; 31(10):1888-92. · 3.69 Impact Factor
Top co-authors
Top Journals
Institutions
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2008
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Case Western Reserve University School of Medicine
Cleveland, OH, USA
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2007
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University of Sydney
- Discipline in Obstetrics and Gynaecology
Sydney, New South Wales, Australia
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2006
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Multiple Myeloma - Institute for Myeloma & Bone Cancer Research
California City, CA, USA
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2005
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Brigham and Women's Hospital
- Brigham and Women’s Center for Brain Mind Medicine
Boston, MA, USA
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