Cancer risk reduction and reproductive concerns in female BRCA1/2 mutation carriers.

BACKGROUND: Women with mutations in the BRCA1 or BRCA2 cancer susceptibility genes face unique choices regarding management of their high risk for breast and ovarian cancer that impact their reproductive options. In order to explore women's preferences for management of elevated cancer risk, we evaluated the decisions of BRCA1/2 mutation carriers about contraception, prophylactic surgery, and family planning. METHODS: An internet-based questionnaire assessing high-risk women's preferences about cancer risk management and reproductive options was designed, pilot-tested and administered electronically to 284 participants of an internet-based advocacy group for women with BRCA1/2 mutations. RESULTS: Two hundred and thirteen eligible participants completed the majority of the survey. Mean age was 34 years; 66% were BRCA1 mutation carriers and 34% were BRCA2 mutation carriers. Most women (92%) had used oral contraceptive pills. About 88% of responders reported frequent or extreme worry about transmitting the mutation to their children. Despite their high level of worry, few responders said they would likely consider using assisted reproduction technologies such as a pregnancy surrogate (3%), cryopreservation of oocytes or embryos (8%), or pre-implantation genetic diagnosis (PGD) to select embryos without BRCA1/2 mutations (13%). CONCLUSIONS: Although they expressed substantial concern about transmitting BRCA1/2 mutations to their children, only a minority of the high-risk women surveyed were likely to consider currently available assisted reproductive strategies. Further research is necessary to explore the risk management preferences of patients with inherited cancer predisposition, and to incorporate these preferences into clinical care.

Effect of oral contraceptives on weight and body composition in young female runners.

PURPOSE: To examine the effect of oral contraceptives (OC) on body weight, fat mass, percent body fat, and lean mass in young female distance runners. METHODS: The study population consisted of 150 female competitive distance runners aged 18-26 yr who had participated in a 2-yr randomized trial of the effect of the OC Lo/Ovral (30 microg of ethinyl estradiol and 0.3 mg of norgestrel) on bone health. Weight and body composition were measured approximately yearly by balance beam scales and dual-energy x-ray absorptiometry, respectively. RESULTS: Women randomized to the OC group tended to gain slightly less weight (adjusted mean difference (AMD) = -0.54 +/- 0.31 kg.yr, P = 0.09) and less fat (AMD = -0.35 +/- 0.25 kg.yr, P = 0.16) than those randomized to the control group. OC assignment was associated with a significant gain in lean mass relative to controls among eumenorrheic women (those who had 10 or more menstrual cycles in the year before baseline; AMD = 0.77 +/- 0.17 kg.yr, P < 0.0001) but not among women with fewer than 10 menstrual cycles in that year (AMD = 0.02 +/- 0.35 kg.yr, P = 0.96). Treatment-received analyses yielded similar results. CONCLUSION: This randomized trial confirms previous findings that OC use does not cause weight or fat mass gain, at least among young female runners. Our finding that this OC is associated with lean mass gain in eumenorrheic runners, but not in those with irregular menses, warrants examination in other studies.

Satellite vegetation index data as a tool to forecast population dynamics of medically important mosquitoes at military installations in the continental United States.

The United States faces many existing and emerging mosquito-borne disease threats, such as West Nile virus and Rift Valley fever. An important component of strategic prevention and control plans for these and other mosquito-borne diseases is forecasting the distribution, timing, and abundance of mosquito vector populations. Populations of many medically important mosquito species are closely tied to climate, and historical climate-population associations may be used to predict future population dynamics. Using 2003-2005 U.S. Army Center for Health Promotion and Preventive Medicine mosquito surveillance data, we looked at populations of several known mosquito vectors of West Nile virus, as well as possible mosquito vectors of Rift Valley fever virus, at continental U.S. military installations. We compared population changes with concurrent patterns for a satellite-derived index of climate (normalized difference vegetation index) and observed instances of population changes appearing to be direct responses to climate. These preliminary findings are important first steps in developing an automated, climate-driven, early warning system to flag regions of the United States at elevated risk of mosquito-borne disease transmission.

Risk factors for stress fracture among young female cross-country runners.

PURPOSE: To identify risk factors for stress fracture among young female distance runners. METHODS: Participants were 127 competitive female distance runners, aged 18-26, who provided at least some follow-up data in a randomized trial among 150 runners of the effects of oral contraceptives on bone health. After completing a baseline questionnaire and undergoing bone densitometry, they were followed an average of 1.85 yr. RESULTS: Eighteen participants had at least one stress fracture during follow-up. Baseline characteristics associated (P<0.10) in multivariate analysis with stress fracture occurrence were one or more previous stress fractures (rate ratio [RR] [95% confidence interval]=6.42 (1.80-22.87), lower whole-body bone mineral content (RR=2.70 [1.26-5.88] per 1-SD [293.2 g] decrease), younger chronologic age (RR=1.42 [1.05-1.92] per 1-yr decrease), lower dietary calcium intake (RR=1.11 [0.98-1.25] per 100-mg decrease), and younger age at menarche (RR=1.92 [1.15-3.23] per 1-yr decrease). Although not statistically significant, a history of irregular menstrual periods was also associated with increased risk (RR=3.41 [0.69-16.91]). Training-related factors did not affect risk. CONCLUSION: The results of this and other studies indicate that risk factors for stress fracture among young female runners include previous stress fractures, lower bone mass, and, although not statistically significant in this study, menstrual irregularity. More study is needed of the associations between stress fracture and age, calcium intake, and age at menarche. Given the importance of stress fractures to runners, identifying preventive measures is of high priority.

The effect of oral contraceptives on bone mass and stress fractures in female runners.

PURPOSE: To determine the effect of oral contraceptives (OC) on bone mass and stress fracture incidence in young female distance runners. METHODS: One hundred fifty competitive female runners ages 18-26 yr were randomly assigned to OC (30 microg of ethinyl estradiol and 0.3 mg of norgestrel) or control (no intervention) for 2 yr. Bone mineral density (BMD) and content (BMC) were measured yearly by dual x-ray absorptiometry. Stress fractures were confirmed by x-ray, magnetic resonance imaging, or bone scan. RESULTS: Randomization to OC was unrelated to changes in BMD or BMC in oligo/amenorrheic (N=50) or eumenorrheic runners (N=100). However, treatment-received analyses (which considered actual OC use) showed that oligo/amenorrheic runners who used OC gained about 1% per year in spine BMD (P<0.005) and whole-body BMC (P<0.005), amounts similar to those for runners who regained periods spontaneously and significantly greater than those for runners who remained oligo/amenorrheic (P<0.05). Dietary calcium intake and weight gain independently predicted bone mass gains in oligo/amenorrheic runners. Randomization to OC was not significantly related to stress fracture incidence, but the direction of the effect was protective in both menstrual groups (hazard ratio [95% CI]: 0.57 [0.18, 1.83]), and the effect became stronger in treatment-received analyses. The trial's statistical power was reduced by higher-than-anticipated noncompliance. CONCLUSION: OC may reduce the risk for stress fractures in female runners, but our data are inconclusive. Oligo/amenorrheic athletes with low bone mass should be advised to increase dietary calcium and take steps to resume normal menses, including weight gain; they may benefit from OC, but the evidence is inconclusive.

Regional bone mineral density in male athletes: a comparison of soccer players, runners and controls.

OBJECTIVES: To investigate the association of soccer playing and long-distance running with total and regional bone mineral density (BMD). DESIGN: Cross-sectional study. SETTING: Academic medical centre. PARTICIPANTS: Elite male soccer players (n = 15), elite male long-distance runners (n = 15) and sedentary male controls (n = 15) aged 20-30 years. MAIN OUTCOME MEASUREMENTS: BMD (g/cm2) of the lumbar spine (L1-L4), right hip, right leg and total body were assessed by dual-energy x-ray absorptiometry, and a scan of the right calcaneus was performed with a peripheral instantaneous x-ray imaging bone densitometer. RESULTS: After adjustment for age, weight and percentage body fat, soccer players had significantly higher whole body, spine, right hip, right leg and calcaneal BMD than controls (p = 0.008, p = 0.041, p<0.001, p = 0.019, p<0.001, respectively) and significantly higher right hip and spine BMD than runners (p = 0.012 and p = 0.009, respectively). Runners had higher calcaneal BMD than controls (p = 0.002). Forty percent of the runners had T-scores of the lumbar spine between -1 and -2.5. Controls were similar: 34% had T-scores below -1 (including 7% with T-scores lower than -2.5). CONCLUSIONS: Playing soccer is associated with higher BMD of the skeleton at all sites measured. Running is associated with higher BMD at directly loaded sites (the calcaneus) but not at relatively unloaded sites (the spine). Specific loading conditions, seen in ball sports or in running, play a pivotal role in skeletal adaptation. The importance of including an appropriate control group in clinical studies is underlined.

Clinical and demographic predictors of long-term disability in patients with relapsing-remitting multiple sclerosis: a systematic review.

OBJECTIVE: To identify clinical and demographic factors associated with long-term disability in patients with relapsing-remitting multiple sclerosis. DATA SOURCES: We searched the MEDLINE (1966-May 2005), EMBASE, CINAHL, Cochrane, and PsycINFO computerized databases, and reviewed reference lists of retrieved articles. STUDY SELECTION: We included studies that examined predictors of long-term disability in patients with relapsing-remitting multiple sclerosis. We excluded studies that did not distinguish relapsing-remitting multiple sclerosis from primary progressive multiple sclerosis, enrolled fewer than 40 subjects, observed subjects for less than 5 years, or collected follow-up information in less than 80% of the inception cohort. DATA EXTRACTION: Two reviewers assessed study quality in 4 domains: cohort assembly, definitions and assessments of prognostic factors and outcomes, and statistical methods. One reviewer extracted data on the direction, magnitude, precision, and statistical significance of the effect of each predictor on prognosis. DATA SYNTHESIS: Heterogeneity of study designs precluded us from pooling the results of 27 eligible studies. Study quality was limited by cross-sectional design, enrollment of prevalent cases from referral centers, and lack of multivariate adjustment. Sphincter symptoms at onset (hazard ratio, 1.1-3.1), incomplete recovery from the first attack (hazard ratio, 1.3-3.3), and a short interval between the first and second attack (hazard ratio, 1.6-1.9) were most strongly and consistently associated with poor prognosis. Other factors widely believed to be of prognostic importance, including sex and age at onset, demonstrated inconsistent or weak effects on prognosis. CONCLUSIONS: The most robust predictors of long-term physical disability in relapsing-remitting multiple sclerosis are sphincter symptoms at onset and early disease course outcomes. These factors can be used to guide treatment decisions for drugs with significant toxicities.

Bartonella spp. in deer keds, Lipoptena mazamae (Diptera: Hippoboscidae), from Georgia and South Carolina, USA.

Deer keds, Lipoptena mazamae (Diptera: Hippoboscidae), were collected from white-tailed deer (Odocoileus virginianus) and humans in Georgia and South Carolina, USA (1 October 2001-6 January 2005) and screened for the presence of DNA from Bartonella spp. Forty deer keds were screened for Bartonella spp. by polymerase chain reaction using primers specific to the riboflavin synthase gene (ribC) of Bartonella. Bartonella species closely related to Bartonella schoenbuchensis and to the etiologic agent of cat-scratch disease (Bartonella henselae) were detected in 10 keds and one ked, respectively.

Disordered eating, menstrual irregularity, and bone mineral density in female runners.

PURPOSE: To examine the relationships between disordered eating, menstrual irregularity, and low bone mineral density (BMD) in young female runners. METHODS: Subjects were 91 competitive female distance runners aged 18-26 yr. Disordered eating was measured by the Eating Disorder Inventory (EDI). Menstrual irregularity was defined as oligo/amenorrhea (0-9 menses per year). BMD was measured by dual x-ray absorptiometry. RESULTS: An elevated score on the EDI (highest quartile) was associated with oligo/amenorrhea, after adjusting for percent body fat, age, miles run per week, age at menarche, and dietary fat, (OR [95% CI]: 4.6 [1.1-18.6]). Oligo/amenorrheic runners had lower BMD than eumenorrheic runners at the spine (-5%), hip (-6%), and whole body (-3%), even after accounting for weight, percent body fat, EDI score, and age at menarche. Eumenorrheic runners with elevated EDI scores had lower BMD than eumenorrheic runners with normal EDI scores at the spine (-11%), with trends at the hip (-5%), and whole body (-5%), after adjusting for differences in weight and percent body fat. Runners with both an elevated EDI score and oligo/amenorrhea had no further reduction in BMD than runners with only one of these risk factors. CONCLUSION: In young competitive female distance runners, (i) disordered eating is strongly related to menstrual irregularity, (ii) menstrual irregularity is associated with low BMD, and (iii) disordered eating is associated with low BMD in the absence of menstrual irregularity.

Effects of ball sports on future risk of stress fracture in runners.

OBJECTIVE: To evaluate whether playing ball sports during childhood and adolescence is associated with the risk of stress fractures in runners later in life. DESIGN: Retrospective cohort study. SETTING: National track and field championships, held at Stanford University. PARTICIPANTS: One hundred fifty-six elite female and 118 elite male distance runners, age 18 to 44 years. INTERVENTIONS: A 1-page questionnaire was used to collect data regarding ages during which athletes played basketball and soccer, as well as other important covariates and outcomes. OUTCOME MEASUREMENTS: Athletes reported the ages when stress fractures occurred. Time to event was defined as the number of years from beginning competitive running to the first stress fracture or to current age, if no fracture had occurred. RESULTS: In both men and women, playing ball sports in youth correlated with reduced stress fracture incidence later in life by almost half, controlling for possible confounders. In men, each additional year of playing ball sports conferred a 13% decreased incidence of stress fracture (adjusted hazard ratio [HR] and 95% confidence interval, 0.87 [0.79-0.95]. Among women with regular menses, the HR for each additional year of playing ball sports was similar: 0.87 (0.75-1.00); however, there was no effect of length of time played among women with irregular menses (HR, 1.03 [0.92-1.16]). In men, younger ages of playing ball sports conferred more protection against stress fractures (HR for each 1-year-older age at first exposure, 1.29 [1.14, 1.45]). CONCLUSIONS: Runners who participate during childhood and adolescence in ball sports may develop bone with greater and more symmetrically distributed bone mass, and with enhanced protection from future stress fractures.