Biomedical subjects

Sarah J Ratcliffe

Publications and source records attributed to Sarah J Ratcliffe.

At least 19 recordsLinked to original sources

PubMed2006

Determinants of serum total and free testosterone levels in women over the age of 65 years.

CONTEXT: Little is known about testosterone (T) levels and their determinants in women of late postmenopausal age. OBJECTIVE: We describe levels of total and free T and selected factors that influence these levels in a random sample of older women. DESIGN: Levels of serum total T and free T by microdialysis were measured using ultrasensitive assays in 347 community-dwelling women aged 65-98 yr enrolled in the Cardiovascular Health Study. Cross-sectional analyses were performed to define factors associated with total and free T levels. RESULTS: In adjusted models: 1) total T levels declined with age until 80, whereas free T levels did not vary by age; 2) women with bilateral oophorectomy had 23% lower total T and 16% lower free T levels than those with at least one intact ovary; 3) oral estrogen users had total and free T levels that were 47% lower than never users; 4) obese women had 47% higher total T and 20% higher free T levels, and overweight women had 24% higher total T and 14% higher free T levels, than normal weight women; and 5) free T levels were 51% higher in black women. Corticosteroid users had 75% lower total T and 43% lower free T levels than nonusers. CONCLUSIONS: Bilateral oophorectomy, estrogen use, corticosteroid use, and low body mass index are independent risk factors for lower T levels in women aged 65 yr and over. Although highly prevalent in women of this age, the physiological significance of low T levels in late postmenopausal women requires further investigation.

Age Distribution↗

PubMed2006

Factors influencing adverse perinatal outcomes in pregnancies achieved through use of in vitro fertilization.

OBJECTIVE: To determine the associations of specific components of IVF treatment with abnormal perinatal outcomes. DESIGN: Case-control study. SETTING: University-based and community-based infertility centers. PATIENT(S): All viable pregnancies achieved through IVF procedures performed between January 1999 and March 2004. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Infertility etiology, gonadotropin exposure, embryo manipulation, and quality. RESULT(S): Of 455 viable pregnancies identified during the study period, 435 met inclusion criteria. While adjusting for maternal age, race, parity, body mass index, infertility center, and year of IVF procedure, multiple gestations were associated with a 12-fold increased risk of poor perinatal outcome compared to singletons. Ovarian hyperstimulation syndrome significantly increased the risk more than 3-fold (odds ratio = 3.14; 95% confidence interval, 1.08-9.14), while endometrial thickness was found to have a significant protective effect (odds ratio = 0.89; 95% confidence interval, 0.80-0.99). We found no effect of etiology of infertility, dose or type of medication used for stimulation, use of embryo-manipulation techniques, or quality on perinatal outcome. CONCLUSION(S): These data confirm and quantify the risk of perinatal morbidity associated with multiple births. After adjusting for multiple births, ovarian hyperstimulation syndrome and suboptimal endometrial development are associated with adverse outcomes in pregnancies achieved through IVF. Our findings suggest that it may be the endometrium rather than the embryo that influences fetal growth and perinatal outcomes after IVF.

Adult↗

PubMed2006

Sex-based differences in myocardial contractile reserve.

Recent studies have identified sex differences in heart function that may affect the risk of developing heart failure. We hypothesized that there are fundamental differences in calcium (Ca) regulation in cardiac myocytes of males and premenopausal females. Isometric force transients (n = 45) were measured at various stimulation frequencies to define the force frequency responses (FFR) (0.5, 1.0, 1.5, and 2.0 Hz) during either changes in bath Ca ([Ca]o) (1.0, 1.75, 3.5, and 7.0 mM) or length-tension (20, 40, 60, 80, and 100% L(max)) in right ventricle trabeculae from normal male (MT) and premenopausal female (FT) cats. Force-Ca measurements were also obtained in chemically skinned trabeculae. Under basal conditions (0.5 Hz, 1.75 mM Ca, 80% L(max)) both MT and FT achieved similar developed forces (DF) (MT 11 +/- 1, FT = 10 +/- 1 mN/mm2). At low rates and lengths, there is no sex difference. At higher preloads and rates, there is a separation in DF in MT and FT. At basal [Ca]o both MT and FT exhibited positive FFR (2.0 Hz, 1.75 mM Ca: MT 38 +/- 3, FT 21 +/- 4 mN/mm2); however, at higher [Ca]o, MT achieved greater DF (2.0 Hz, 7.0 mM Ca: MT 40 +/- 3 and FT = 24 +/- 4 mN/mm2). We detected no sex difference in myofilament Ca sensitivity at a sarcomere length of 2.1 mum. However, rapid cooling contractures indicated greater sarcoplasmic reticulum (SR) Ca load in MT at higher frequencies. Despite virtually identical contractile performance under basal conditions, significant sex differences emerge under conditions of increased physiological stress. Given the lack of sex differences in myofilament Ca sensitivity, these studies suggest fundamental sex differences in cellular Ca regulation to achieve contractile reserve, with myocardium from males exhibiting higher SR Ca load.

Actin Cytoskeleton↗

PubMed2006

Comparison of cool tip versus 8-mm tip catheter in achieving electrical isolation of pulmonary veins for long-term control of atrial fibrillation: a prospective randomized pilot study.

OBJECTIVE: To compare safety and efficacy of 8-mm versus cooled tip catheter in achieving electrical isolation (EI) of pulmonary veins (PV) for long-term control of atrial fibrillation (AF). BACKGROUND: There is paucity of studies comparing safety/efficacy of 8-mm and cooled tip catheters in patients undergoing AF ablation. METHODS AND RESULTS: This was a randomized and patient-blinded study. Subjects were followed by clinic visits (at 6 weeks and 6 months) and transtelephonic monitoring (3-week duration) done around each visit. Primary endpoints were: (1) long-term AF control (complete freedom and/or >90% reduction in AF burden on or off antiarrhythmic drugs at 6 months after a single ablation), and (2) occurrence of serious adverse events (cardiac tamponade, stroke, LA-esophageal fistula, and/or death). Eighty-two patients (age 56 +/- 9 years, 60 males, paroxysmal AF = 59) were randomized (42 patients to 8-mm tip and 40 patients to cooled tip). EI of PVs was achieved in shorter time by the 8-mm tip as compared with cooled tip catheter (40 +/- 23 minutes vs 50 +/- 30 minutes; P < 0.05) but long-term AF control was not different between the two (32 patients [78%] vs 28 patients [70%], respectively; P = NS). One serious adverse event occurred in each group (LA-esophageal fistula and stroke, respectively) and no significant PV stenosis was observed in either. CONCLUSION: EI of PVs using either 8-mm or cooled tip catheter results in long-term AF control in the majority after a single ablation procedure, with comparable efficacy and safety.

Atrial Fibrillation↗

PubMed2006

Is vaginal birth after cesarean (VBAC) or elective repeat cesarean safer in women with a prior vaginal delivery?

OBJECTIVE: This study was undertaken to determine whether vaginal birth after cesarean (VBAC) or elective repeat cesarean delivery is safer overall for a woman with a prior vaginal delivery. STUDY DESIGN: This retrospective cohort study of pregnant women from 1996 to 2000 who had a prior cesarean delivery, was conducted in 17 centers. Trained nurses extracted historical and maternal outcome data on subjects by using standardized tools. This planned secondary analysis examined the subcohort that had also previously undergone a vaginal delivery, comparing those who underwent a VBAC trial with those who elected to have a repeat cesarean delivery. Outcomes included uterine rupture, bladder injury, fever, transfusion and a composite (uterine rupture, bladder injury, and artery laceration). We performed bivariate and multivariable analyses. RESULTS: Of 6619 patients with a prior cesarean delivery who had also had a prior vaginal delivery, 5041 patients attempted a VBAC delivery and 1578 had an elective cesarean delivery. Although there was no significant difference in uterine rupture or bladder injury between the two groups, women who underwent a VBAC attempt were less likely to experience the composite adverse maternal outcome, have a fever, or require a transfusion. CONCLUSION: Among VBAC candidates who have had a prior vaginal delivery, those who attempt a VBAC trial have decreased risk for overall major maternal morbidities, as well as maternal fever and transfusion requirement compared with women who elect repeat cesarean delivery. Physicians should make this more favorable benefit-risk ratio explicit when counseling this patient subpopulation on a trial of labor.

Adult↗

PubMed2006

Clinically silent cerebral ischemic events after cardiac surgery: their incidence, regional vascular occurrence, and procedural dependence.

BACKGROUND: The reported frequency of stroke after coronary artery bypass grafting varies between 1.5% and 6%, approaches 10% after aortic valve replacement, and may occur in between 40 to 70% in high-risk groups. Clinically silent infarction may be far more frequent and could contribute to long-term cognitive dysfunction in patients after cardiac procedures. Using diffusion-weighted magnetic resonance imaging we document the occurrence, vascular distribution, and procedural dependence of silent infarction after cardiac surgery with cardiopulmonary bypass. We also document the association of preexisting white matter lesions with new postoperative ischemic lesions. METHODS: Thirty-four patients underwent T2-weighted fluid attenuated inversion recovery and diffusion-weighted magnetic resonance imaging before and after cardiac surgery with cardiopulmonary bypass for coronary artery bypass grafting, aortic valve replacement, and mitral valve repair or replacement surgery. Images were evaluated by experienced neuroradiologists for number, size, and vascular distribution of lesions. RESULTS: Mean age of participants was 67 +/- 15 years. Imaging occurred before and 6 +/- 2 days after surgery. New cerebral infarctions were evident in 6 of 34 patients (18%), were often multiple, and in 67% of patients were clinically silent. The occurrence of new infarctions by surgical procedure was as follows: aortic valve replacement (2 of 6), coronary artery bypass grafting and aortic valve replacement (3 of 8), aortic valve replacement with root replacement (1 of 1), coronary artery bypass grafting and mitral valve repair or replacement (0 of 4), mitral valve repair or replacement (0 of 2), and isolated coronary artery bypass grafting (0 of 13). New infarction occurred in 6 of 15 (40%) of all procedures involving aortic valve replacement. The severity of preexisting white matter lesions trended toward predicting the occurrence of new lesions (p = 0.055). CONCLUSIONS: Diffusion-weighted imaging reveals new cerebral infarctions in nearly 40% of patients after aortic valve replacement.

Aged↗

PubMed2006

Aging: impact upon local cerebral oxygenation and blood flow with acute isovolemic hemodilution.

Data from the neurosurgical critical care arena demonstrate a correlation between cerebral oxygenation, survival, and cognitive function. Transfusion may increase and hemodilution decrease cerebral oxygenation. Both acute and chronic anemia have been associated with cognitive dysfunction. Aggressive blood conservation protocols have been instituted across all age groups without conclusive evidence for their impact upon outcome. Aged subjects are at the greatest risk of cognitive sequelae after major surgery associated with significant blood loss. We hypothesize that cerebral physiologic changes associated with "normal" aging may compromise cerebral oxygenation in the presence of severe anemia.Fischer 344 rats, the NIH National Institute of Aging normal aging rat model, underwent a stepwise isovolemic hemodilution protocol. Age groups (Age Grp) studied were as follows: Age Grp-A (3 months), n=14; Age Grp-B (9 to 12 months), n=14; and Age Grp-C (24 months), n=14. Brain oxygen tension (PBrO2), laser Doppler flow, and mean arterial pressure were measured. Final hemoglobin averaged 6.1+/-0.9 g/dL. PBrO2 levels decreased from a baseline of 18.1+/-4.1 to 17.5+/-6.8 mm Hg (P=0.49), and laser Doppler flow increased by 18+/-20% (P<0.0001) after hemodilution. Employing repeated measures multiple regression, Age Grp (P=0.30) was not a significant controlling covariate of PBrO2 in response to isovolemic hemodilution. PBrO2 levels were actually higher in Age Grp-C animals at all time points of the hemodilution protocol, although this was not statistically significant. Aged animals were also fully capable of mounting a robust local cerebral hyperemic response to the anemic challenge that was not separable from the response of younger animals.

Aging↗

PubMed2006

Psychometric properties of the Post-Fall Index.

Evaluation and prevention of falls begin with a thorough understanding of their occurrence. Post-fall assessment (PFA) tools should be available to sufficiently guide nursing staff in identification of all possible causes. Absence of empirically tested PFA tools led to the development of the Post-Fall Index (PFI). Developed and validated in three phases, a 76-item PFI was first tested for content validity by national experts. Next, it was tested for feasibility with registered nurses practicing in nursing homes. Last, it was piloted with a sample of 30 falls by older residents of a skilled nursing unit in a continuing care retirement community. Review of data from these 30 falls provided the item analysis. Reflective of evidenced-based guidelines, a 30-item PFI emerged, containing essential items causing falls. Although lengthier than incident reports, its comprehensiveness was deemed of higher value. Large absolute agreement of items (70%-100%) indicates good interrater reliability. The PFI is valid, reliable, and feasible and has clinical utility for the secondary prevention of falls.

Accidental Falls↗

PubMed2006

Incidence of type 1 diabetes in Philadelphia is higher in black than white children from 1995 to 1999: epidemic or misclassification?

OBJECTIVE: To determine the epidemiology of type 1 diabetes in children in Philadelphia, Pennsylvania, from 1995 through 1999 and compare these data with previous cohorts. RESEARCH DESIGN AND METHODS: This is a report of a retrospective population-based registry maintained since 1985. Hospital records meeting the following criteria were reviewed: newly diagnosed type 1 diabetes, age 0-14 years, residing in Philadelphia at the time of diagnosis, and diagnosed from 1 January 1995 to 31 December 1999. The secondary source of validation was the School District of Philadelphia. Incidence rates by race and age were compared with 1985-1989 and 1990-1994 cohorts. RESULTS: A total of 234 case subjects were identified, and the registry was determined to be 96% complete. The overall age-adjusted incidence rate in Philadelphia was 14.8 per 100,000/year. Incidence rates in Hispanic children (15.5 per 100,000/year) and white children (12.8 per 100,000/year) have been relatively stable over 15 years. The incidence in black children (15.2 per 100,000/year), however, has increased dramatically, rising 64% in children 5-9 years of age (14.9 per 100,000/year) and 37% in the 10- to 14-year age-group (26.9 per 100,000/year). CONCLUSIONS: The overall incidence of type 1 diabetes in Philadelphia is increasing and is similar to other U.S. registries. These are the first data reporting a higher incidence in black children in a registry of children 0-14 years of age. The etiology of the marked increase in incidence in the black population is unknown and underscores the need to establish type 1 diabetes as a reportable disease, so that environmental risk factors may be thoroughly investigated.

Adolescent↗

PubMed2005

Maternal complications with vaginal birth after cesarean delivery: a multicenter study.

OBJECTIVE: This study was undertaken to determine incidence and risk factors for uterine rupture in women attempting vaginal birth after cesarean delivery (VBAC) in a wide range of hospital settings. STUDY DESIGN: We performed a case-control study nested within a cohort of women who have had a prior cesarean to determine the incidence and risk factors for uterine rupture in women attempting VBAC. RESULTS: The incidence rate of uterine rupture in those who attempt VBAC was 9.8 per 1000. A prior vaginal delivery was associated with a lower risk of uterine rupture (adjusted odds ratio [OR] = 0.40, 95% CI 0.20-0.81). Although prostaglandins alone were not associated with uterine rupture, sequential use of prostaglandin and pitocin was associated with uterine rupture (adjusted OR = 3.07, 95% CI 0.98-9.88). CONCLUSION: Women with a prior cesarean should be offered VBAC, and women with a prior cesarean and prior vaginal delivery should be encouraged to VBAC. Although other studies have suggested that prostaglandins should be avoided, we suggest that inductions requiring sequential agents be avoided.

Adult↗

PubMed2005

An exploratory study of depression among older African American users of an academic outpatient rehabilitation program.

Variation in the presentation of depressive illness among older African Americans may complicate assessment of depression, especially among those with multiple medical comorbidities and functional disabilities. The purpose of this study was to explore the prevalence of depression among older poor African Americans attending an academic outpatient rehabilitation program, using a depression measure with low somatic item content. Correlates of depression in this population also were explored. Health-care records of 150 older African Americans seen over a 2-year period were examined. Depression was assessed on admission using the 30-item Geriatric Depression Scale (GDS). Using a GDS cutoff score for depression of 11 or higher, 30% of the sample (age 75.5 +/- 7.16 years, range 65-95, 75% women) scored positive for depression. Nine percent also reported having suicidal thoughts within the previous week. Consistent with existing literature, depressed patients, as compared to nondepressed patients, were significantly younger, more suicidal, more likely to rate their general health as poor, had higher mean ratings of pain, and more often limited their social activities. Six GDS items were found to have little ability to discriminate between depressed and nondepressed patients: satisfaction with life, getting bored easily, prefer staying at home, find life exciting, getting started on new projects, and full of energy. The authors recommend further testing of the GDS with similar populations of older, poor, medically ill, and functionally disabled older adults.

Academic Medical Centers↗

PubMed2004

Joint modeling of longitudinal and survival data via a common frailty.

We develop a joint model for the analysis of longitudinal and survival data in the presence of data clustering. We use a mixed effects model for the repeated measures that incorporates both subject- and cluster-level random effects, with subjects nested within clusters. A Cox frailty model is used for the survival model in order to accommodate the clustering. We then link the two responses via the common cluster-level random effects, or frailties. This model allows us to simultaneously evaluate the effect of covariates on the two types of responses, while accounting for both the relationship between the responses and data clustering. The model was motivated by a study of end-stage renal disease patients undergoing hemodialysis, where we wished to evaluate the effect of iron treatment on both the patients' hemoglobin levels and survival times, with the patients clustered by enrollment site.

Algorithms↗

PubMed2004

Deviations from the population-averaged versus cluster-specific relationship for clustered binary data.

There has been much debate about the relative merits of mixed effects and population-averaged logistic models. We present a different perspective on this issue by noting that the investigation of the relationship between these models for a given dataset offers a type of sensitivity analysis that may reveal problems with assumptions of the mixed effects and/or population-averaged models for clustered binary response data in general and longitudinal binary outcomes in particular. We present several datasets in which the following violations of assumptions are associated with departures from the expected theoretical relationship between these two models: 1) negative intra-cluster correlations; 2) confounding of the response-covariate relationship by cluster effects; and 3) confounding of autoregressive relationships by the link between baseline outcomes and subject effects. Under each of these conditions, the expected theoretical attenuation of the population-averaged odds ratio relative to the cluster-specific odds ratio does not necessarily occur. In all cases, the naive fitting of a random intercept logistic model appears to lead to bias. In response, the random intercept model is modified to accommodate negative intra-cluster correlations, confounding due to clusters, or baseline correlations with random effects. Comparisons are made with GEE estimation of population-averaged models and conditional likelihood estimation of cluster-specific models. Several examples, including a cross-over trial, a multicentre nonrandomized treatment study, and a longitudinal observational study are used to illustrate these modifications.

Animals↗

PubMed2003

Precision of the CASL-perfusion MRI technique for the measurement of cerebral blood flow in whole brain and vascular territories.

PURPOSE: To analyze the precision of cerebral blood flow (CBF) measurements made with continuous arterial spin labeling(CASL) perfusion magnetic resonance imaging (MRI) over experimentally relevant intervals. MATERIALS AND METHODS: CASL perfusion MRI measurements of CBF on a 1.5-T GE Signa magnet were repeated in young healthy male and female subjects at one hour and one week. Precision of the measurement was evaluated at both time intervals. RESULTS: CASL perfusion MRI measurements of CBF yielded within-subject coefficients of variation (wsCV) of 5.8% for global and 13% for individual vascular regions when measurements were repeated within one hour. Differences in these values represent the error in post-processing. Global and regional CBF measurements over one week yielded wsCVs of 13% and 14%, respectively. At one week, error secondary to physiologic variability affected global and regional measurements to the same degree and masked the software post-processing error seen at one hour. The magnitude of the difference in repeated measures correlated with the magnitude of the measurement. CONCLUSION: CASL perfusion MRI CBF measurements are accurate and precise. Variability over longer periods of time appears attributable to physiologic factors. Repeatability of the CASL measurement is sensitive to the magnitude of the measurement. This should be taken into account when studies requiring repeated measures involve subjects with significant variability in CBF.

Adult↗

PubMed2002

Functional data analysis with application to periodically stimulated foetal heart rate data. I: functional regression.

Functional regression is used to model longitudinal data where the number of measurements on the functional covariate is much greater than the number of subjects in the study. Thus, functional regression can be thought of as singular longitudinal analysis. We have modified existing functional regression techniques to the case of a functional covariate with a repeated stimulus. We applied this modified functional regression to periodically stimulated foetal heart rates. The heart rate tracings were used as a predictor of the child's psychomotor development at approximately 18 months of age. In the past, this type of data has been analysed using the partially subjective concept of habituation. By using the entire heart rate tracings through functional regression, we have the advantage that habituation does not need to be defined and all available information is used to predict later child development.

Adult↗

PubMed2002

Functional data analysis with application to periodically stimulated foetal heart rate data. II: functional logistic regression.

We present a basis solution for the modelling of a binary response with a functional covariate plus any number of scalar covariates. This can be thought of as singular longitudinal data analysis as there are more measurements on the functional covariate than subjects in the study. The maximum likelihood parameter estimates are found using a basis expansion and a modified Fisher scoring algorithm. This technique has been extended to model a functional covariate with a repeated stimulus. We used periodically stimulated foetal heart rate tracings to predict the probability of a high risk birth outcome. It was found that these tracings could predict 94.1 per cent of the high risk pregnancies and without the stimulus, the heart rates were no more predictive than chance.

Adult↗

PubMedDate not supplied

Acceptance of hepatitis B vaccination by pregnant adolescents.

PURPOSE: To determine (1) the rate of prenatal hepatitis B virus (HBV) vaccine acceptance in HBV nonimmune pregnant adolescents, (2) if postulated behavioral and attitudinal factors are associated with HBV vaccine, and (3) the rate of actual receipt of HBV vaccine postpartum in eligible subjects. DESIGN AND METHODS: During 1999-2000, at an inner-city tertiary-care center prenatal clinic, 160 HBV nonimmune adolescents <18 years who were receiving prenatal and delivery care at the center were identified. The research nurse provided an HBV information pamphlet and offered immediate in-hospital postpartum HBV vaccination. Risk factors for nonacceptance of the vaccine were measured with structured questionnaires and medical record review documenting care attendance. Subsequently, all subjects, irrespective of prenatal acceptance of vaccine, were offered vaccine before postpartum discharge, and the rate of actual acceptance was determined. RESULTS: In these predominantly African American (95%) adolescents, the rate of vaccine acceptance was 91%. Actual vaccination rate was 86%, but it was not associated with prior acceptance of vaccination or behavioral or attitudinal factors. CLINICAL IMPLICATIONS: Acceptance of vaccination and actual vaccination were high in this population of high-risk adolescents. The authors found that reoffering vaccine was a successful intervention, even with adolescents who had less-than-optimal attendance at prenatal visits. Given the high rate of acceptance and vaccination in this setting, the authors would encourage public health programs to implement vaccination programs in adolescent prenatal clinics and to offer vaccination postpartum to those who do not receive it prenatally.

Adolescent↗

PubMedDate not supplied

Ethical conflict in nurse practitioners and physician assistants in managed care.

BACKGROUND: More patients are receiving healthcare services from nurse practitioners (NPs) and physician assistants (PAs). These providers are likely to be confronted with a variety of ethical issues as they balance quality care with their patients' rising cost concerns. However, very little is known about the ethical conflicts and causes of these conflicts experienced by these clinicians in their daily practice. OBJECTIVE: To identify ethical concerns and conflicts NPs and PAs encounter related to managed care in the delivery of primary care to patients and the factors that influence ethical conflict. METHODS: A cross-sectional self-administered mailed questionnaire was sent to 3,900 NPs and PAs randomly selected from primary care and primary care subspecialties in the United States (adjusted response rate, 50.6%). Respondents were surveyed on ethical issues and concerns, ethics preparedness, and ethical conflict. Bivariate and multiple linear regression analyses were used to evaluate predictors of ethical conflict. RESULTS: Insurance constraints were reported to have interfered with the ability to provide quality patient care by 72% of respondents, with 55.3% reporting daily to weekly interferences. Nearly half of respondents (47%) have been asked by a patient to mislead insurers to assist them in receiving care. A perceived obligation to advocate for patients, even if it means exaggerating the severity of a patient's condition, was the single most significant predictor of ethical conflict, explaining 25% of the variance. DISCUSSION: NPs and PAs are experiencing ethical conflict often associated with their perceived professional obligations to advocate for patients. Being well-prepared in ethics and having sufficient professional independence help clinicians balance the ethical complexities and demands of meeting patients' needs within a constrained healthcare system.

Adult↗