Pharmacokinetics of 23-epi-26-deoxyactein in women after oral administration of a standardized extract of black cohosh.

Dietary supplements containing black cohosh are alternatives to conventional hormone replacement therapy in menopause. This study investigates the maximum tolerated dose of a 75% ethanol extract of black cohosh and determines the pharmacokinetics of one of its most abundant triterpene glycosides, 23-epi-26-deoxyactein. Single doses of black cohosh extract containing 1.4, 2.8, or 5.6 mg of 23-epi-26-deoxyactein were administered to 15 healthy, menopausal women. Serial blood samples and 24-h urine samples were obtained; blood chemistry, hormonal levels, and 23-epi-26-deoxyactein levels were determined. No acute toxicity or estrogenic hormone effects were observed. Pharmacokinetic analyses of 23-epi-26-deoxyactein in sera indicated that the maximum concentration and area under the curve increased proportionately with dosage, and that the half-life was ~2 h for all dosages. Less than 0.01% of the 23-epi-26-deoxyactein was recovered in urine 24 h after administration. No phase I or phase II metabolites were observed either in clinical specimens or in vitro.

Soy and red clover for mid-life and aging.

INTRODUCTION: Menopause is associated with mid-life, a time when many women begin to experience the signs and symptoms of aging, such as increases in blood pressure, changes in lipid profiles, loss of bone mass density, and diminished memory and cognition. Given the result of the Women's Health Initiative, many women no longer consider hormone therapy the first option for promoting healthy aging. Instead, they are turning to botanical and dietary supplement (BDS) products in place of hormone therapy. This paper reviews the evidence available for use of isoflavones from soy and red clover for the treatment or prevention of these health issues. METHODS: The MEDLINE and EMBASE databases were searched for articles relating to soy or red clover supplement use for prevention and/or treatment of heart disease, hyperlipidemia, osteoporosis, mood disorders and cognitive abilities. Studies were included if they were randomized, controlled trials and included peri- or postmenopausal women. RESULTS: Isoflavone products appear to be the most useful for improving lipid profiles; however, the evidence suggests that isoflavone extracts from soy are less effective than products containing soy protein or red clover isoflavones. Soy protein appears to reduce levels of total cholesterol and low density lipoprotein cholesterol, while red clover reduces levels of triglycerides and increases high density lipoprotein cholesterol. The data were somewhat less convincing, although promising, for increasing bone mass density and improving cognitive abilities. CONCLUSIONS: Research suggests that isoflavones found in soy foods and red clover appear to have a small but positive health effect on plasma lipid concentrations, bone mass density, and cognitive abilities. Given the lack of serious safety concerns in the short term, it would appear that including soy and red clover in the diet of postmenopausal women, not withstanding a soy allergy, might be beneficial.

Drape estimation vs. visual assessment for estimating postpartum hemorrhage.

OBJECTIVE: To compare (1) visual estimation of postpartum blood loss with estimation using a specifically designed blood collection drape and (2) the drape estimate with a measurement of blood loss by photospectrometry. METHODS: A randomized controlled study was performed with 123 women delivered at the District Hospital, Belgaum, India. The women were randomized to visual or drape estimation of blood loss. A subsample of 10 drape estimates was compared with photospectrometry results. RESULTS: The visual estimate of blood loss was 33% less than the drape estimate. The interclass correlation of the drape estimate to photospectrometry measurement was 0.92. CONCLUSION: Drape estimation of blood loss is more accurate than visual estimation and may have particular utility in the developing world. Prompt detection of postpartum hemorrhage may reduce maternal morbidity and mortality in low-resource settings.

A descriptive model of preventability in maternal morbidity and mortality.

OBJECTIVE: To develop a descriptive model of preventability for maternal morbidity and mortality that can be used in quality assurance and morbidity and mortality review processes. STUDY DESIGN: This descriptive study was part of a larger case-control study conducted at the University of Illinois at Chicago in which maternal deaths were cases and women with severe maternal morbidity served as controls. Morbidities and mortalities were classified by a team of clinicians as preventable or not preventable. Qualitative analysis of data was conducted to identify and categorize different types of preventable events. RESULTS: Of 237 women, there were 79 women with preventable events attributable to provider or system factors. The most common types of preventable events were inadequate diagnosis/recognition of high-risk (54.4%), treatment (38.0%), and documentation (30.7%). CONCLUSIONS: A descriptive model was illustrated that can be used to categorize preventable events in maternal morbidity and mortality and can be incorporated into quality assurance and clinical case review to enhance the monitoring of hospital-based obstetric care and to decrease medical error.

Postpartum hemorrhage in resource-poor settings.

Despite the strong interest of international health agencies, worldwide maternal mortality has not declined substantially over the past 10 years. Postpartum hemorrhage (PPH) is the most common cause of maternal death across the world, responsible for more than 25% of deaths annually. Although effective tools for prevention and treatment of PPH are available, most are not feasible or practical for use in the developing world where many births still occur at home with untrained birth attendants. Application of many available clinical solutions in rural areas would necessitate substantial changes in government infrastructure and in local culture and customs surrounding pregnancy and childbirth. Before treatment can be administered, prompt and accurate diagnosis must be made, which requires training and appropriate blood measurement tools. After diagnosis, appropriate interventions that can be applied in remote settings are needed. Many uterotonics known to be effective in reducing PPH in tertiary care settings may not be useful in community settings because they require refrigeration and/or skilled administration. Moreover, rapid transfer to a higher level of care must be available, a challenge in many settings because of distance and lack of transportation. In light of these barriers, low-technological replacements for treatments commonly applied in the developed-world must be utilized. Community education, improvements to emergency care systems, training for birth attendants, misoprostol, and Uniject have shown promise as potential solutions. In the short term, it is expedient to capitalize on practical opportunities that utilize the existing strengths and resources in each community or region in order to implement appropriate solutions to save the lives of women during childbirth.

Conducting international collaborative research in developing nations.

International research partnerships bring together some of the best and the brightest in an effort to tackle global health problems. Such collaborations also pose complex challenges, such as maintaining ethical principles in the conduct of research in developing nations. In implementing a randomized clinical trial to reduce postpartum hemorrhage (PPH) during childbirth in rural India, U.S. and Indian collaborators addressed three such issues: the appropriateness of an ethical randomized controlled trial in the developing world, the inclusion of a placebo arm, and the relevance of informed consent in a semiliterate rural population.

Chemical and biological characterization and clinical evaluation of botanical dietary supplements: a phase I red clover extract as a model.

Botanical dietary supplements, as compared with nutritional supplements or single-component pharmaceutical drugs, are typically less-refined preparations derived from bulk plant material and, as such, require a modified approach to their development, production, and evaluation. An integrated, multidisciplinary team of scientific and clinical investigators is required in order to develop high quality phytomedicines and rigorously evaluate their safety and efficacy. Research on botanicals involves unique challenges as plant source materials frequently vary in chemical content and may contain unwanted pesticides, heavy metals, contaminant plant species, or other adulterants. Ideally, a botanical formulation should be standardized, both chemically and biologically, by a combination of analytical techniques and bioassays. This combination approach provides multiple measures by which reproducible quality and efficacy of botanical supplements may be achieved, and is particularly useful for botanical products for which the active compound(s) have not yet been identified. Safety and toxicity should be evaluated during the supplement development process in both in vitro and in vivo systems. A number of liquid chromatography-mass spectrometry methods can aid in the assessment of purity, bioavailability, toxicity, metabolism, and molecular target profiling of botanical extracts. Clinical investigators must appreciate the complexity of multi-component phytomedicines and adjust trial protocols accordingly. This review highlights practical considerations of value to basic science and clinical investigators engaged in the study of botanical supplements. Lessons and examples are drawn from the authors' experience in designing and developing a red clover (Trifolium pratense L.) standardized extract for evaluation in Phase I and Phase II clinical trials.

Knowledge, beliefs, and risk factors for osteoporosis among African-American and Hispanic women.

The purpose of this work was to develop and conduct a needs and risk instrument to assess knowledge of osteoporosis risk factors, identify beliefs and attitudes about this disease, and delineate the presence and/or absence of healthy behaviors associated with osteoporosis among African American and Hispanic women. The survey findings suggest that African-American and Hispanic women are not well-versed in behaviors that would promote and maintain optimal bone mass. Consequently, they are not practicing appropriate lifestyle and dietary habits to decrease their risk of osteoporosis. Such behaviors include inadequate physical activity, inadequate calcium intake, cigarette smoking, and long-term steroid use. Less than 10% of women in the study were getting adequate daily dietary calcium intake, with only 13% taking daily calcium supplements to augment this deficit and less than one-half of women exercising at a minimal level (20 minutes/3 times a week). Women in this study also had limited knowledge about osteoporosis, perceived this condition to be less of a health threat as compared to breast cancer, heart disease, diabetes, and Alzheimer's disease, and very few had the perception that being Hispanic or African American was a factor to consider in assessing their risk of osteoporosis. Our findings suggest that osteoporosis education and prevention initiatives are needed, specifically for African-American and Hispanic women, to promote healthy behaviors, identify women at-risk, and encourage early diagnosis and treatment.

Maternal deaths in an urban perinatal network, 1992-1998.

OBJECTIVE: The object of this study was to use an in-depth peer-review process to determine the maternal mortality ratio at a single urban perinatal center and to identify factors associated with fatal outcomes to elucidate opportunities for preventive measures to reduce the maternal mortality ratio. STUDY DESIGN: Between 1992 and 1998 all maternal deaths occurring within our perinatal network were identified. A peer-review committee was established to review all available data for each death to determine the underlying cause of death, whether it was related to pregnancy, and whether the death was potentially preventable. RESULTS: There were 131,500 births and 42 maternal deaths, for a maternal mortality ratio of 31.9 maternal deaths per 100,000 live births. The adjusted pregnancy-related maternal mortality ratio was 22.8 maternal deaths per 100,000 live births, with 37% of those deaths (11/30) deemed potentially preventable and a provider factor cited in >80% of these. Pulmonary embolus and cardiac disease together accounted for 40% of the pregnancy-related deaths. CONCLUSION: Local maternal mortality ratios identified through a peer-review process indicate that the magnitude of the problem is much greater than is recognized through national death certificate data. The high proportion of potentially preventable maternal deaths indicates the need for improvement in both patient and provider education if we are to reduce the maternal mortality ratio to 3.3 maternal deaths per 100,000 live births, the stated national health goal of Healthy People 2000.

Differences in menstrual bleeding characteristics, functional status, and attitudes toward menstruation in three groups of women.

This report examines differences in bleeding characteristics, functional status, and attitudes toward menstruation among three groups of women: (1) women who complain of abnormal uterine bleeding (AUB), (2) women who have similar menstrual patterns as those complaining of AUB but who do not perceive themselves to have abnormal bleeding, and (3) women without evidence of prolonged or excessive bleeding. Women who complain of AUB and women with heavy bleeding but not complaining of AUB, although similar on two important menstrual symptoms (very heavy bleeding or episodes of unusually heavy bleeding) differ on a number of other menstrual characteristics, including the frequency of short cycles, the probability of having an abnormally long period, and reporting of unusually heavy bleeding lasting longer than 1 day. Whether women reported concerns with menstruation or not, the majority of women in this analysis had fairly negative attitudes toward menstruation. However, this negativity toward menstruation did not translate into women wanting a hysterectomy, even for those with heavy bleeding. The major difference among the three groups of women was the strong negative effect of AUB on functional status. A majority of women complaining of AUB reported that the bleeding interfered significantly with their daily routine, making them unable to function at work and at home. These results suggest that although the main complaint of women with AUB is very heavy bleeding, a number of other specific menstrual characteristics differentiate women with AUB from other women with very heavy bleeding who do not perceive the bleeding to be problematic. The complaint of AUB appears to be related to how significantly bleeding affects daily functioning. Therefore, an important factor to assess when considering treatment of AUB is the extent to which bleeding symptoms significantly affect functional status.

The decision-making process for the treatment of abnormal uterine bleeding.

This pilot study was conducted to investigate the treatment decision-making process of patients and physicians for abnormal uterine bleeding (AUB). Frequently, women with AUB are referred for hysterectomy without diagnostic workup, alternative therapeutic management, or patient input (i.e., patient treatment preferences). Variations in treatment strategies used for patients may be related to a number of factors external to the patient's underlying disease. However, little is known about which factors are most influential or about the extent to which they influence physicians' and patients' decisions. We prospectively followed the management and treatment of 52 women with complaints of AUB and examined differences in treatment among these patients. Extensive previsit interviews were conducted with these women to identify each patient's symptoms, health status, functional status, and preferences for and expectations of treatment. We then conducted telephone interviews within a week of the visit and again 9-12 months later to determine the treatment plan, patient level of participation in and satisfaction with the treatment, symptoms, and functional status. Overall, our findings suggest that patients want to be involved in making treatment decisions and that when women were presented with alternatives to hysterectomy, many chose alternative medical therapy or other surgical procedures. In addition, women reported that these alternative treatments produced significant improvement in symptom intensity and functioning. Increased patient participation in decision making enhanced patient satisfaction. These findings suggest that hysterectomy rates may be decreased by offering women alternative treatments and by finding ways to increase women's participation in their treatment decisions.

The influence of psychosocial factors on heart transplantation decisions and outcomes.

In January 1990, a well-established heart transplant program added a psychosocial evaluation procedure to its medical evaluation of potential transplant recipients. To determine the predictive value of psychosocial evaluation for decisions to list patients for a transplant and for ultimate clinical outcomes, we reviewed records of 191 patients who underwent psychosocial evaluation in the subsequent 3 years. Informal prescreening for obvious psychopathology and other disqualifiers almost certainly restricted the ranges of psychosocial factors observed in the sample. Of 120 patients listed, 61 actually received transplants. Psychosocial factors were little used in deciding whether to list the patients and were not predictive of recipients' medical outcome or compliance, but were moderately predictive of complication rates and difficulty of managing patients after transplantation. Although psychosocial evaluation of prescreened potential transplant recipients has little value in predicting medical outcome, it may be useful for planning and scheduling care after transplantation.

The impact of nonclinical factors on practice variations: the case of hysterectomies.

OBJECTIVE: This study investigates the role of nonclinical factors (physician characteristics) in explaining variations in hysterectomy practice patterns. DATA SOURCES AND STUDY SETTING: Patient discharge data are obtained from the Arizona state discharge database for the years 1989-1991. Physician data are obtained from the Arizona State Medical Association. The analyses are based on 36,104 cases performed by 339 physicians in 43 hospitals. STUDY DESIGN: This article measures the impact of physician factors on the decision to perform a hysterectomy, controlling for a host of patient and hospital characteristics. Physician factors include background characteristics and training, medical experience, and physician's practice style. Physician effects are evaluated in terms of their overall contribution to the explanatory power of regression models, as well as in terms of specific hypotheses to be tested. DATA COLLECTION: The sources of data were linked to produce one record per patient. PRINCIPAL FINDINGS: As a set, physician factors account for a statistically significant increase in the explanatory power of the model after addition of patient and hospital effects. Parameter estimates provide further support for the hypothesized effects of physicians' background, experience, and practice characteristics. CONCLUSIONS: Overall, the results confirm that nonclinical (physician) factors play a statistically significant role in the hysterectomy decision. Substantively, however, these factors play a smaller, secondary role compared to that of clinical and patient factors in explaining practice variations in hysterectomies. The results suggest that efforts to reduce unnecessary hysterectomies should be directed at identifying the appropriate clinical indications for hysterectomy and disseminating this information to physicians and patients. This may require such intervention strategies as continuing clinical education, promulgation of explicit practice guidelines, peer review, public education, and greater understanding and inclusion of patient preference in the decision process.

The effect of physician factors on the cesarean section decision.

The number of deliveries by cesarean section (c-section) has increased dramatically. Clinical and demographic factors have not adequately explained the increased rate, however. This study investigates the role of nonclinical (i.e., physician) factors in explaining variations in c-section rates, including the physician's training/experience, financial and convenience incentives, and practice characteristics. The study measures the impact of these factors on the decision to perform a c-section rather than opting for vaginal delivery, controlling for a host of patient and hospital characteristics. Physician effects are evaluated in terms of their overall contribution to the explanatory power of logistic regression models, as well as in terms of specific hypotheses to be tested. The analyses are based on 33,233 deliveries performed by 441 physicians in 36 hospitals in 1 state during 1989. As a set, physician factors contribute more to the explanatory power of the model than do hospital factors, despite being added last to the equation. Parameter estimates provide more support for the hypothesized effects of physician convenience incentives than background/training. The log odds of performing a c-section increase with the physician's rate of c-sections in the prior year, delivery on a Friday, and delivery between 6 AM and 6 PM, and decrease with the concentration of the physician's hospital practice. Patient factors appear much more important than both physician and hospital factors, however. Efforts to reduce unnecessary c-sections should focus on identifying the appropriate clinical indications for c-section and disseminating this information to physicians.

[The utilization of Arizona medical services by residents of Mexico]. / Utilización de servicios médicos de Arizona por residentes de México.

Arizona physicians practicing in the four counties bordering Mexico were surveyed regarding the use of their services by residents of Mexico. One hundred eighty-eight (79%) of the 239 respondents to the mail survey reported seeing at least one Mexican resident per week during 1988. Ninety-nine of these physicians (53%) practiced in Tucson; 89 (47%) practiced elsewhere in the four border counties. The mean number of Mexican resident patients seen per week was nine (9% of total) for border physicians and 5 (6% of total) for Tucson physicians. The most frequent responses from border physicians asked to list the most common health conditions of their Mexican resident patients were injury and poisoning (21%) and circulatory diseases (11%), while the most frequent responses of Tucson physicians were circulatory diseases (10%) and digestive diseases (9%). Problems and solutions in the border care health system are mainly related to quality of care and health care financing.

The treatment perspectives of physicians, citizens, and state legislators.

This study addresses the dilemma of physicians to act both as an agent of their patients and as an agent of society. We contrasted the perceptions of physicians, citizens at large, and state legislators about 11 topics related to physician decision making regarding the management of care for seriously ill patients. Significant and interpretable differences were found between physicians and citizens, although there were no differences between these two groups and the state legislators. However, even the obtained differences were fewer and smaller than expected. These results suggest that lay, legislative, and medical viewpoints may be less at odds with each other than the literature would suggest, and reaching an accord on at least some aspects of health policy may not be as difficult as generally is assumed.