Papers by Sarah Ratcliffe
Acta paediatrica (Oslo, Norway : 1992), Jan 2, 2017
The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception, Jan 8, 2016
To evaluate the impact peer counselling has on same-day desire for long-acting, reversible contra... more To evaluate the impact peer counselling has on same-day desire for long-acting, reversible contraception (LARC) among adolescents attending a family planning clinic. A randomised, controlled trial of 110 adolescent females attending an outpatient clinic for contraception in 2013. Adolescents received either brief peer counselling about LARC with routine contraceptive counselling, or routine counselling alone. Bivariate analyses and multivariable logistic regression assessed the primary outcome of same-day desire for LARC and secondary outcomes of change in knowledge and attitudes regarding LARC. Peer counselling was well received and 70% reported that it was helpful in contraceptive decision-making. Peer counselling did not affect same-day desire for LARC, however, adolescents who received the intervention were more likely to report increased knowledge and positive change in attitudes towards LARC (adjusted odds ratios: 6.6 (95% confidence interval: 2.0-22.0 and 6.4 (1.6-26.8), resp...
PLOS Pathogens, 2016
The loss of HIV-specific CD8+ T cell cytolytic function is a primary factor underlying progressiv... more The loss of HIV-specific CD8+ T cell cytolytic function is a primary factor underlying progressive HIV infection, but whether HIV-specific CD8+ T cells initially possess cytolytic effector capacity, and when and why this may be lost during infection, is unclear. Here, we assessed CD8+ T cell functional evolution from primary to chronic HIV infection. We observed a profound expansion of perforin+ CD8+ T cells immediately following HIV infection that quickly waned after acute viremia resolution. Selective expression of the effector-associated transcription factors T-bet and eomesodermin in cytokine-producing HIV-specific CD8+ T cells differentiated HIV-specific from bulk memory CD8+ T cell effector expansion. As infection progressed expression of perforin was maintained in HIV-specific CD8+ T cells with high levels of T-bet, but not necessarily in the population of T-betLo HIV-specific CD8+ T cells that expand as infection progresses. Together, these data demonstrate that while HIV-specific CD8+ T cells in acute HIV infection initially possess cytolytic potential, progressive transcriptional dysregulation leads to the reduced CD8+ T cell perforin expression characteristic of chronic HIV infection.
Stroke, 2016
Stroke is a potentially devastating complication of cardiac surgery. Identifying predictors of ra... more Stroke is a potentially devastating complication of cardiac surgery. Identifying predictors of radiographic infarct may lead to improved stroke prevention for surgical patients. We reviewed 129 postoperative brain magnetic resonance imagings from a prospective study of patients undergoing surgical aortic valve replacement. Acute infarcts were classified as watershed or embolic using prespecified criteria. Acute infarct on magnetic resonance imaging was seen in 79 of 129 patients (61%), and interrater reliability for stroke pathogenesis was high (κ=0.93). Embolic infarcts only were identified in 60 patients (46%), watershed only in 2 (2%), and both in 17 (13%). In multivariable logistic regression, embolic infarct was associated with aortic arch atheroma (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.0-12.0; P=0.055), old subcortical infarcts (OR, 5.5; 95% CI, 1.1-26.6; P=0.04), no history of percutaneous transluminal coronary angioplasty or coronary artery bypass graft (OR, 4.0; 95% CI, 1.2-13.7; P=0.03), and higher aortic valve gradient (OR, 1.3 per 5 mm Hg; 95% CI, 1.09-1.6; P=0.004). Watershed infarct was associated with internal carotid artery stenosis ≥70% (OR, 11.7; 95% CI, 1.8-76.8; P=0.01) and increased left ventricular ejection fraction (OR, 1.6 per 5% increase; 95% CI, 1.08-2.4; P=0.02). The principal mechanism of acute cerebral infarction after aortic valve replacement is embolism. There are distinct factors associated with watershed and embolic infarct, some of which may be modifiable.
Statistics in medicine, Jan 20, 2015
We extend a random pattern mixture joint model for longitudinal ordinal outcomes and informative ... more We extend a random pattern mixture joint model for longitudinal ordinal outcomes and informative dropouts. The patients are generalized to 'pattern' groups based on known covariates that are potentially surrogated for the severity of the underlying condition. The random pattern effects are defined as the latent effects linking the dropout process and the ordinal longitudinal outcome. Conditional on the random pattern effects, the longitudinal outcome and the dropout times are assumed independent. Estimates are obtained via the Expectation-maximization algorithm. We applied the model to the end-stage renal disease data. Anemia was found to be significantly affected by the baseline iron treatment when the dropout information was adjusted via the study model; as opposed to an independent or shared parameter model. Simulations were performed to evaluate the performance of the random pattern mixture model under various assumptions. Copyright © 2015 John Wiley & Sons, Ltd.
Journal of Virology, 2013
Journal of Leukocyte Biology, 2013
In this study, we compared the immunogenicity and protection from repeated low-dose intrarectal S... more In this study, we compared the immunogenicity and protection from repeated low-dose intrarectal SIVmac251 challenge in two groups of vaccinated RMs. Animals were immunized with live SIVmac239, which had been attenuated by a deletion of the nef sequence, or they were vaccinated twice with an E1-deleted AdHu5, expressing SIVmac239gag. The vaccinated animals and a cohort of unvaccinated control animals were then challenged 10 times in weekly intervals with low doses of SIVmac251 given rectally. Our results confirm previous studies showing that whereas SIVΔnef provides some degree of protection against viral acquisition after repeated low-dose rectal SIVmac251 challenges, vaccination with an AdHu5gag vaccine designed to induce only antiviral T cell responses is ineffective. As immunological analyses of prechallenge, vaccine-induced T and B cell responses failed to reveal correlates of protection that distinguished the more susceptible from the more resistant vaccinated animals, we carried out RNA-Seq studies of paired pre- and postvaccination samples to identify transcriptional patterns that correlated with the differences in response. We show that gene expression signatures associated with the delayed SIV infection seen in some AdHu5gag recipients were largely present in prevaccination samples of those animals. In contrast, the responding SIVΔnef-immunized animals showed a predominance of vaccine-induced changes, thus enabling us to define inherited and vaccine-induced gene expression signatures and their associated pathways that may play a role in preventing SIV acquisition.
The Journal of Immunology, 2009
Subscription http://jimmunol.org/subscription is online at: The Journal of Immunology Information... more Subscription http://jimmunol.org/subscription is online at: The Journal of Immunology Information about subscribing to Permissions
JAMA, Jan 6, 2017
Predictions of long-term survival and functional outcomes influence decision making for criticall... more Predictions of long-term survival and functional outcomes influence decision making for critically ill patients, yet little is known regarding their accuracy. To determine the discriminative accuracy of intensive care unit (ICU) physicians and nurses in predicting 6-month patient mortality and morbidity, including ambulation, toileting, and cognition. Prospective cohort study conducted in 5 ICUs in 3 hospitals in Philadelphia, Pennsylvania, and enrolling patients who spent at least 3 days in the ICU from October 2013 until May 2014 and required mechanical ventilation, vasopressors, or both. These patients' attending physicians and bedside nurses were also enrolled. Follow-up was completed in December 2014. ICU physicians' and nurses' binary predictions of in-hospital mortality and 6-month outcomes, including mortality, return to original residence, ability to toilet independently, ability to ambulate up 10 stairs independently, and ability to remember most things, think ...
Applied clinical informatics, 2016
Eliciting knowledge from geographically dispersed experts given their time and scheduling constra... more Eliciting knowledge from geographically dispersed experts given their time and scheduling constraints, while maintaining anonymity among them, presents multiple challenges. Describe an innovative, Internet based method to acquire knowledge from experts regarding patients who need post-acute referrals. Compare, 1) the percentage of patients referred by experts to percentage of patients actually referred by hospital clinicians, 2) experts' referral decisions by disciplines and geographic regions, and 3) most common factors deemed important by discipline. De-identified case studies, developed from electronic health records (EHR), contained a comprehensive description of 1,496 acute care inpatients. In teams of three, physicians, nurses, social workers, and physical therapists reviewed case studies and assessed the need for post-acute care referrals; Delphi rounds followed when team members did not agree. Generalized estimating equations (GEEs) compared experts' decisions by dis...
Muscle & nerve, Jan 7, 2016
Friedreich ataxia (FRDA) leads to increased risk of diabetes. Less is known regarding the dynamic... more Friedreich ataxia (FRDA) leads to increased risk of diabetes. Less is known regarding the dynamics of glucose homeostasis in FRDA, the influence of disease features, and the utility of oral-based metrics for capturing metabolic dysfunction. To examine these dynamics, we analyzed oral and intravenous glucose tolerance test data in 42 non-diabetic patients with FRDA. Patients showed high insulin responsiveness to glucose and low insulin sensitivity. Genetic severity predicted overall metabolic impairment: individuals with longer guanineadenine-adenine (GAA) repeats on the shorter allele showed a lower disposition index. Genetic severity did not predict any other variables. Measures of disposition index from intravenous and oral glucose tolerance testing did not correlate well, possibly reflecting divergent responses to oral and IV glucose loads. FRDA patients demonstrate abnormal compensatory activity for managing glucose. Genetic severity impacts the global homeostatic profile, where...
Sleep, Jan 29, 2016
The goal of this study was to examine different paradigms for determining critical closing pressu... more The goal of this study was to examine different paradigms for determining critical closing pressures (Pcrit). Methods of determining Pcrit were compared, including direct observation of occluded (no flow) breaths versus inferring Pcrit from extrapolated data, and Pcrit generated by aggregating pressure-flow data from multiple runs versus Pcrit averaged across individual pressure-flow runs. The relationship between Pcrit and obstructive sleep apnea (OSA) was examined. A total of 351 participants with and without OSA underwent overnight polysomnography with pressure-flow measurements to determine Pcrit. A series of filters were applied to raw data to provide consistent, objective criteria for determining which data to include in Pcrit calculations. Observed Pcrit values were computed as the mean nasal pressure level at which a subject had at least two breaths with peak inspiratory flow < 50 mL/sec. Extrapolated Pcrit was calculated in two ways: (1) separately for each individual ru...
American journal of respiratory and critical care medicine, 2014
Public Health Nutrition, 2011
To describe patterns of food consumption associated with overweight/obesity (OW/OB) and their lin... more To describe patterns of food consumption associated with overweight/obesity (OW/OB) and their links to socio-economic status (SES) and urbanization. A nationwide cross-sectional survey. Secondary schools in cities, towns and villages in Botswana, Africa. A total of 746 adolescent schoolchildren. OW/OB is associated with greater SES, city residence and a snack-food diet pattern. Students belonging to higher SES compared with those from a lower SES background reported significantly (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0·01) more daily servings of snack foods (1·55 v. 0·76) and fewer servings of traditional diet foods (0·99 v. 1·68) and also reported that they ate meals outside the home more often (90% v. 72%). Students in cities ate significantly (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0·01) more servings of snacks (1·69 v. 1·05 v. 0·51) and fewer servings of traditional foods (0·67 v. 1·52 v. 1·61) compared with those in urban and rural villages. The odds of OW/OB were increased 1·16-fold with a snack-food diet, a result that was diminished when controlled for SES. These data suggest that nutritional transition occurs at different rates across urbanization and SES levels in Botswana. In cities, increasing the availability of fruit while reducing access to or portion sizes of snack items is important. Emphasis on continued intake of traditional foods may also be helpful as rural areas undergo economic and infrastructural development.
Journal of Pediatric Nursing, 2012
in comparison with our general Type 1 diabetes population. The data collection tool included mult... more in comparison with our general Type 1 diabetes population. The data collection tool included multiple sociodemographic factors, HbA1c, and markers of the degree of DKA. Results: We reviewed a total of 167 patients with an admitting diagnosis of DKA; 63 charts were excluded because they did not meet either DKA criteria and age criteria, had new-onset diabetes, or lived outside of West Virginia; 57% were female, 43% male. Average age was 13.6 years (SD = 2.81 years); 56% were covered by Medicaid or CHIPS insurance and 44% by commercial payers; 11.5% were African American and 88.5% were Caucasian. The average HbA1c was 10.85% (SD = 2.364). Average length of stay in the PICU was 17.8 hours (SD = 11.13). We identified peak DKA admissions during April to October, with the lowest admissions being December through March. Conclusions: Salient findings include higher HbA1c and higher rates in African American patients and in those covered by Medicaid/CHIPS. Clinical Implications: This study identifies sociodemographic factors associated with children admitted for DKA in West Virginia. Patients indentified to be at higher risk for DKA include those with elevated HbA1c, of African American race, and covered by Medicaid/ CHIPS. Nurses can utilize these findings to develop strategies to educate these high-risk groups on the prevention of DKA.
AIDS Patient Care and STDs, 2009
The purpose of this study was to assess the feasibility and acceptability of an HIV risk reductio... more The purpose of this study was to assess the feasibility and acceptability of an HIV risk reduction intervention to increase consistent condom use in a sample of older HIV-positive African American men who have sex with men (MSM). Repeated measures were used at baseline, immediate postintervention, and 3 months postintervention to collect data. The development of the intervention was implemented in four phases: focus groups, pilot testing of the questionnaire, modifying the intervention, and executing the intervention. Sixty HIV-positive African American MSM were randomized to either an HIV risk condition or a health condition. Each condition consisted of four 120-minute sessions delivered over a 4-week period in a classroom-like setting using interactive approaches. The primary outcome was consistent condom use during every instance of anal intercourse. In unadjusted analyses, men in the risk reduction group were twice as likely to use condoms consistently (odds ratio [OR] = 2.04; 95% confidence interval [CI] = 0.48-8.77; p = 0.336), although this did not reach statistical significance. All participants reporting consistent condom use at baseline reported consistent use at 3 months giving perfect prediction for the sample. Among men not reporting consistent condom use at baseline, those in the risk reduction group were 5 times more likely to report consistent condom use at 3 months than were those in the health condition (OR = 5.18; 95% CI = 0.97-27.78; p = 0.054). The findings suggest that an HIV risk-reduction condition may increase consistent condom use among HIV-positive African American MSM 50 years and older.
Jaids Journal of Acquired Immune Deficiency Syndromes, Mar 1, 2008
Macrophages are important targets for HIV-1 and R5X4 strains play a central role in pathogenesis,... more Macrophages are important targets for HIV-1 and R5X4 strains play a central role in pathogenesis, especially in late-stage patients who may receive the fusion inhibitor T20. Sensitivity to T20 varies markedly among HIV-1 strains and is influenced by both viral and cellular factors that affect Env/ CD4/coreceptor interactions. We addressed the relationship between T20 inhibition and pathway by which R5X4 HIV-1 infect primary macrophages, which express both coreceptors. In U87/CD4/ coreceptor cells T20 sensitivity for entry through CCR5 and CXCR4 were correlated. In macrophages, the proportion of total entry mediated by each coreceptor differed among isolates. However, neither pathway was uniformly more or less sensitive to T20, nor did the proportion of entry mediated by each coreceptor predict T20 sensitivity. T20 sensitivity for macrophage infection overall correlated modestly with that for entry through CCR5 but not CXCR4, but unlike U87 cells, sensitivity of entry through CCR5 and CXCR4 were not correlated. These results suggest that strainspecific factors influence R5X4 T20 sensitivity regardless of coreceptor used; an absence of systematic differences in efficiency by which R5X4 strains use the two coreceptors; and that efficiency/kinetics of interactions with CCR5 are a central determinant of macrophage entry even when both pathways are utilized.
Data Revues 00029378 V192i4 S000293780500058x, Aug 18, 2011
Objective: This study was undertaken to compare clinical outcomes in women with 1 versus 2 prior ... more Objective: This study was undertaken to compare clinical outcomes in women with 1 versus 2 prior cesarean deliveries who attempt vaginal birth after cesarean delivery (VBAC) and also to compare clinical outcomes of women with 2 prior cesarean deliveries who attempt VBAC or opt for a repeat cesarean delivery. Study design: We performed a secondary analysis of a retrospective cohort study, in which the medical records of more than 25,000 women with a prior cesarean delivery from 16 community and tertiary care hospitals were reviewed by trained nurse abstractors. Information on demographics, obstetric history, medical and social history, and the outcomes of the index pregnancy was obtained. Comparisons of obstetric outcomes were made between women with 1 versus 2 prior cesarean deliveries, and also between women with 2 prior cesarean deliveries who opt for VBAC attempt versus elective repeat cesarean delivery. Both bivariate and multivariate techniques were used for these comparisons. Results: The records of 20,175 women with one previous cesarean section and 3,970 with 2 prior cesarean sections were reviewed. The rate of VBAC success was similar in women with a single prior cesarean delivery (75.5%) compared with those with 2 prior cesarean deliveries (74.6%), though the odds of major morbidity were higher in those with 2 prior cesarean deliveries (adjusted odd ratio[OR] = 1.61 95% CI 1.11-2.33). Among women with 2 prior cesarean deliveries, those who opt for a VBAC attempt had higher odds of major complications compared with those who opt for elective repeat cesarean delivery (adjusted OR = 2.26, 95% CI 1.17-4.37). Conclusion: The likelihood of major complications is higher with a VBAC attempt in women with 2 prior cesarean deliveries compared with those with a single prior cesarean delivery. In women with 2 prior cesarean deliveries, while major complications are increased in those who
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Papers by Sarah Ratcliffe