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1.  An empirical derivation of the optimal time interval for defining ICU readmissions 
Medical care  2013;51(8):706-714.
ICU readmission rates are commonly viewed as indicators of ICU quality. However, definitions of ICU readmissions vary, and it is unknown which, if any, readmissions are associated with ICU quality.
Empirically derive the optimal interval between ICU discharge and readmission for purposes of considering ICU readmission as an ICU quality indicator.
Research Design
Retrospective cohort study
214,692 patients discharged from 157 U.S. ICUs participating in the Project IMPACT database, 2001–2008.
We graphically examined how patient characteristics and ICU discharge circumstances (e.g., ICU census) were related to the odds of ICU readmissions as the allowable interval between ICU discharge and readmission was lengthened. We defined the optimal interval by identifying inflection points where these relationships changed significantly and permanently.
2,242 patients (1.0%) were readmitted to the ICU within 24 hours; 9062 (4.2%) within 7 days. Patient characteristics exhibited stronger associations with readmissions after intervals greater than 48–60 hours. By contrast, ICU discharge circumstances and ICU interventions (e.g. mechanical ventilation) exhibited weaker relationships as intervals lengthened, with inflection points at 30 to 48 hours. Due to the predominance of afternoon readmissions regardless of time of discharge, using intervals defined by full calendar days rather than fixed numbers of hours produced more valid results.
It remains uncertain whether ICU readmission is a valid quality indicator. However, having established two full calendar days (not 48 hours) following ICU discharge as the optimal interval for measuring ICU readmissions, this study will facilitate future research designed to determine its validity.
PMCID: PMC3714373  PMID: 23698182
ICU quality indicators; benchmarking; ICU readmission; outcomes assessment; outcomes research; outcomes assessment; quality assessment; critical care
2.  Increased Mucosal CD4+ T Cell Activation in Rhesus Macaques following Vaccination with an Adenoviral Vector 
Journal of Virology  2014;88(15):8468-8478.
The possibility that vaccination with adenovirus (AdV) vectors increased mucosal T cell activation remains a central hypothesis to explain the potential enhancement of HIV acquisition within the Step trial. Modeling this within rhesus macaques is complicated because human adenoviruses, including human adenovirus type 5 (HAdV-5), are not endogenous to macaques. Here, we tested whether vaccination with a rhesus macaque-derived adenoviral vector (simian adenovirus 7 [SAdV-7]) enhances mucosal T cell activation within rhesus macaques. Following intramuscular SAdV-7 vaccination, we observed a pronounced increase in SAdV-7-specific CD4+ T cell responses in peripheral blood and, more dramatically, in rectal mucosa tissue. Vaccination also induced a significant increase in the frequency of activated memory CD4+ T cells in SAdV-7- and HAdV-5-vaccinated animals in the rectal mucosa but not in peripheral blood. These fluctuations within the rectal mucosa were also associated with a pronounced decrease in the relative frequency of naive resting CD4+ T cells. Together, these results indicate that peripheral vaccination with an AdV vector can increase the activation of mucosal CD4+ T cells, potentially providing an experimental model to further evaluate the role of host-vector interactions in increased HIV acquisition after AdV vector vaccination.
IMPORTANCE The possibility that vaccination with a human adenovirus 5 vector increased mucosal T cell activation remains a central hypothesis to explain the potential enhancement of human immunodeficiency virus (HIV) acquisition within the Step trial. In this study, we tested whether vaccination with a rhesus macaque-derived adenoviral vector in rhesus macaques enhances mucosal CD4+ T cell activation, the main cell target of simian immunodeficiency virus (SIV)/HIV. The results showed that vaccination with an adenoviral vector indeed increases activation of mucosal CD4+ T cells and potentially increases susceptibility to SIV infection.
PMCID: PMC4135938  PMID: 24829340
3.  Serial Echocardiography in Very Preterm Infants: A Pilot Randomized Trial 
Acta paediatrica (Oslo, Norway : 1992)  2013;102(11):10.1111/apa.12389.
To determine whether routine echocardiography increases diagnosis and treatment of patent ductus arteriosus (PDA) and whether randomized non-disclosure is a feasible strategy for studying PDA management.
2 center pilot randomized, controlled trial. 88 infants with birth weights ≤1250 grams and gestational ages ≤30 weeks were randomized to disclosure or non-disclosure of serial echocardiogram findings. Echocardiograms were performed at 3–5 and 7–10 days of life. The primary outcome was time to regain birth weight.
100% of echocardiograms in the disclosure group were disclosed; 16% (echocardiogram #1) and 29% (echocardiogram #2) were disclosed in the non-disclosure group. There was a statistically non-significant decrease in drug therapy for PDA in the non-disclosure group (adjusted odds ratio [AOR] 0.56, 95% confidence interval [CI] 0.24–1.34). There was no difference in time to regain birth weight or in other important neonatal outcomes. However, infants in the non-disclosure group were more likely to demonstrate appropriate weight loss and then regain birth weight within 7–14 days (AOR 2.64, 95% CI 1.08–6.44).
Randomized non-disclosure of echocardiograms is a feasible strategy for evaluation of approaches to PDA management in very preterm infants. Avoidance of routine echocardiography may reduce drug therapy for PDA without adverse clinical effects.
PMCID: PMC3867206  PMID: 23952100
Echocardiogram; Echocardiography; Patent ductus arteriosus; Very low birth weight infant; Very premature infant
4.  An Empirical Comparison of Key Statistical Attributes Among Potential ICU Quality Indicators* 
Critical care medicine  2014;42(8):1821-1831.
Good quality indicators should have face validity, relevance to patients, and be able to be measured reliably. Beyond these general requirements, good quality indicators should also have certain statistical properties, including sufficient variability to identify poor performers, relative insensitivity to severity adjustment, and the ability to capture what providers do rather than patients' characteristics. We assessed the performance of candidate indicators of ICU quality on these criteria. Indicators included ICU readmission, mortality, several length of stay outcomes, and the processes of venous-thromboembolism and stress ulcer prophylaxis provision.
Retrospective cohort study
One hundred thirty-eight U.S. ICUs from 2001-2008 in the Project IMPACT database.
Two hundred sixty-eight thousand eight hundred twenty-four patients discharged from U.S. ICUs.
Measurements and Main Results
We assessed indicators' (1) variability across ICU-years; (2) degree of influence by patient vs. ICU and hospital characteristics using the Omega statistic; (3) sensitivity to severity adjustment by comparing the area under the receiver operating characteristic curve (AUC) between models including vs. excluding patient variables, and (4) correlation between risk adjusted quality indicators using a Spearman correlation. Large ranges of among-ICU variability were noted for all quality indicators, particularly for prolonged length of stay (4.7–71.3%) and the proportion of patients discharged home (30.6–82.0%), and ICU and hospital characteristics outweighed patient characteristics for stress ulcer prophylaxis (ω, 0.43; 95% CI, 0.34–0.54), venous thromboembolism prophylaxis (ω, 0.57; 95% CI, 0.53–0.61), and ICU readmissions (ω, 0.69; 95% CI, 0.52–0.90). Mortality measures were the most sensitive to severity adjustment (area under the receiver operating characteristic curve % difference, 29.6%); process measures were the least sensitive (area under the receiver operating characteristic curve % differences: venous thromboembolism prophylaxis, 3.4%; stress ulcer prophylaxis, 2.1%). None of the 10 indicators was clearly and consistently correlated with a majority of the other nine indicators.
No indicator performed optimally across assessments. Future research should seek to define and operationalize quality in a way that is relevant to both patients and providers.
PMCID: PMC4212919  PMID: 24717464
critical care; ICU quality indicators; outcome measures; process measures; quality and patient safety; quality improvement
5.  Outcomes Among Patients Discharged From Busy Intensive Care Units 
Annals of internal medicine  2013;159(7):447-455.
Strains on the capacities of intensive care units (ICUs) may influence the quality of ICU-to-floor transitions.
To determine how 3 metrics of ICU capacity strain (ICU census, new admissions, and average acuity) measured on days of patient discharges influence ICU length of stay (LOS) and post–ICU discharge outcomes.
Retrospective cohort study from 2001 to 2008.
155 ICUs in the United States.
200 730 adults discharged from ICUs to hospital floors.
Associations between ICU capacity strain metrics and discharged patient ICU LOS, 72-hour ICU readmissions, subsequent in-hospital death, post–ICU discharge LOS, and hospital discharge destination.
Increases in the 3 strain variables on the days of ICU discharge were associated with shorter preceding ICU LOS (all P < 0.001) and increased odds of ICU readmissions (all P< 0.050). Going from the 5th to 95th percentiles of strain was associated with a 6.3-hour reduction in ICU LOS (95% CI, 5.3 to 7.3 hours) and a 1.0% increase in the odds of ICU readmission (CI, 0.6% to 1.5%). No strain variable was associated with increased odds of subsequent death, reduced odds of being discharged home from the hospital, or longer total hospital LOS.
Long-term outcomes could not be measured.
When ICUs are strained, triage decisions seem to be affected such that patients are discharged from the ICU more quickly and, perhaps consequentially, have slightly greater odds of being readmitted to the ICU. However, short-term patient outcomes are unaffected. These results suggest that bed availability pressures may encourage physicians to discharge patients from the ICU more efficiently and that ICU readmissions are unlikely to be causally related to patient outcomes.
Primary Funding Source
Agency for Healthcare Research and Quality; National Heart, Lung, and Blood Institute; and Society of Critical Care Medicine.
PMCID: PMC4212937  PMID: 24081285
6.  Mortality among Patients Admitted to Strained Intensive Care Units 
Rationale: The aging population may strain intensive care unit (ICU) capacity and adversely affect patient outcomes. Existing fluctuations in demand for ICU care offer an opportunity to explore such relationships.
Objectives: To determine whether transient increases in ICU strain influence patient mortality, and to identify characteristics of ICUs that are resilient to surges in capacity strain.
Methods: Retrospective cohort study of 264,401 patients admitted to 155 U.S. ICUs from 2001 to 2008. We used logistic regression to examine relationships of measures of ICU strain (census, average acuity, and proportion of new admissions) near the time of ICU admission with mortality.
Measurements and Main Results: A total of 36,465 (14%) patients died in the hospital. ICU census on the day of a patient’s admission was associated with increased mortality (odds ratio [OR], 1.02 per standardized unit increase; 95% confidence interval [CI]: 1.00, 1.03). This effect was greater among ICUs employing closed (OR, 1.07; 95% CI: 1.02, 1.12) versus open (OR, 1.01; 95% CI: 0.99, 1.03) physician staffing models (interaction P value = 0.02). The relationship between census and mortality was stronger when the census was composed of higher acuity patients (interaction P value < 0.01). Averaging strain over the first 3 days of patients’ ICU stays yielded similar results except that the proportion of new admissions was now also associated with mortality (OR, 1.04 for each 10% increase; 95% CI: 1.02, 1.06).
Conclusions: Several sources of ICU strain are associated with small but potentially important increases in patient mortality, particularly in ICUs employing closed staffing models. Although closed ICUs may promote favorable outcomes under static conditions, they are susceptible to being overwhelmed by patient influxes.
PMCID: PMC3826272  PMID: 23992449
critical care; resource allocation; intensive care unit; physician staffing; regionalization
7.  Increasing Incidence of Type 1 Diabetes in Youth 
Diabetes Care  2013;36(6):1597-1603.
The purpose of this study was to describe the incidence of type 1 diabetes in children in Philadelphia from 2000–2004, compare the epidemiology to the previous three cohorts in the Philadelphia Pediatric Diabetes Registry, and, for the first time, describe the incidence of type 2 diabetes.
Diabetes cases were obtained through a retrospective population-based registry. Hospital inpatient and outpatient records were reviewed for cases of type 1 and type 2 diabetes diagnosed from 1 January 2000 to 31 December 2004. The secondary source of validation was the School District of Philadelphia. Time series analysis was used to evaluate the changing pattern of incidence over the 20-year period.
The overall age-adjusted incidence rate in 2000–2004 of 17.0 per 100,000 per year was significantly higher than that of previous cohorts, with an average yearly increase of 1.5% and an average 5-year cohort increase of 7.8% (P = 0.025). The incidence in white children (19.2 per 100,000 per year) was 48% higher than in the previous cohort. Children aged 0–4 years had a 70% higher incidence (12.2 per 100,000 per year) than the original cohort; this increase was most marked in young black children. The overall age-adjusted incidence of type 2 diabetes was 5.8 per 100,000 per year and was significantly higher in black children.
The incidence of type 1 diabetes is rising among children in Philadelphia. The incidence rate has increased by 29% since the 1985–1989 cohort. The most marked increases were among white children ages 10–14 years and black children ages 0–4 years. The incidence of type 1 diabetes is 18 times higher than that of type 2 in white children but only 1.6 times higher in black children.
PMCID: PMC3661835  PMID: 23340888
8.  Conducting Research Using the Electronic Health Record Across Multi-Hospital Systems: Semantic Harmonization Implications for Administrators 
Administrators play a major role in choosing and managing the use of the electronic health record (EHR). The documentation policies and EHR changes enacted or approved by administrators affect the ability to use clinical data for research. This article illustrates the challenges that can be avoided through awareness of the consequences of customization, variations in documentation policies and quality, and user interface features. Solutions are posed that assist administrators in avoiding these challenges and promoting data harmonization for research and quality improvement.
PMCID: PMC3714548  PMID: 23708504
9.  Developing a Model of the Benefits and Burdens of Research Participation in Cancer Clinical Trials 
AJOB primary research  2012;3(2):10-23.
Recruiting and retaining human participants in cancer clinical trials is challenging for many investigators. Although we expect participants to identify and weigh the benefits and burdens of research participation for themselves, it is not clear what burdens adult cancer participants perceive in relation to benefits. We identify key attributes and develop an initial conceptual framework of benefit and burden based on interviews with individuals enrolled in cancer clinical research.
Semistructured interviews were conducted with a purposive sample of 32 patients enrolled in cancer clinical trials at a large northeastern cancer center. Krueger's guidelines for qualitative methodology were followed.
Respondents reported a range of benefits and burdens associated with research participation. Benefits such as access to needed medications that subjects otherwise might not be able to afford, early detection and monitoring of the disease, potential for remission or cure, and the ability to take control of their lives through actively participating in the trial were identified. Burdens included the potentiality of side effects, worry and fear of the unknown, loss of job support, and financial concerns.
Both benefit and burden influence research participation, including recruitment and retention in clinical trials. Dimensions of benefit and burden include physical, psychological, economic, familial, and social. Understanding the benefit-burden balance involved in the voluntary consent of human subjects is a fundamental tenet of research and important to ensure that subjects have made an informed decision regarding their decision to participate in clinical research.
PMCID: PMC3989990  PMID: 24748992
benefits; burdens; cancer; clinical trials; qualitative methods
10.  Immunological and Virological Analyses of Rhesus Macaques Immunized with Chimpanzee Adenoviruses Expressing the Simian Immunodeficiency Virus Gag/Tat Fusion Protein and Challenged Intrarectally with Repeated Low Doses of SIVmac 
Journal of Virology  2013;87(17):9420-9430.
Human adenovirus (AdHu)-based candidate AIDS vaccine can provide protection from simian immunodeficiency virus (SIV) transmission and disease progression. However, their potential use may be limited by widespread preexisting immunity to the vector. In contrast, preexisting immunity to chimpanzee adenoviruses (AdC) is relatively rare. In this study, we utilized two regimens of prime-boost immunizations with AdC serotype SAd-V23 (also called AdC6) and SAd-V24 (also called AdC7) expressing SIV Gag/Tat to test their immunogenicity and ability to protect rhesus macaques (RMs) from a repeated low-dose SIVmac239 challenge. Both AdC6 followed by AdC7 (AdC6/7) and AdC7 followed by AdC6 (AdC7/6) induced robust SIV Gag/Tat-specific T cell responses as measured by tetramer staining and functional assays. However, no significant protection from SIV transmission was observed in either AdC7/6- or AdC7/6-vaccinated RMs. Interestingly, in the RMs showing breakthrough infections, AdC7/6-SIV immunization was associated with a transient but significant (P = 0.035 at day 90 and P = 0.033 at day 120 postinfection) reduction in the setpoint viral load compared to unvaccinated controls. None of the measured immunological markers (i.e., number or functionality of SIV-specific CD8+ and CD4+ T cell responses and level of activated and/or CCR5+ CD4+ target cells) at the time of challenge correlated with protection from SIV transmission in the AdC-SIV-vaccinated RMs. The robust immunogenicity observed in all AdC-immunized RMs and the transient signal of protection from SIV replication exhibited by AdC7/6-vaccinated RMs even in the absence of any envelope immunogen suggest that AdC-based vectors may represent a promising platform for candidate AIDS vaccines.
PMCID: PMC3754116  PMID: 23804645
11.  Use of mobile telemedicine for cervical cancer screening 
Visual inspection of the cervix with application of 4% acetic acid (VIA) is an inexpensive alternative to cytology-based screening in areas where resources are limited, such as in many developing countries. We have examined the diagnostic agreement between off-site (remote) expert diagnosis using photographs of the cervix (photographic inspection with acetic acid, PIA) and in-person VIA. The images for remote evaluation were taken with a mobile phone and transmitted by MMS. The study population consisted of 95 HIV-positive women in Gaborone, Botswana. An expert gynaecologist made a definitive positive or negative reading on the PIA results of 64 out of the 95 women whose PIA images were also read by the nurse midwives. The remaining 31 PIA images were deemed insufficient in quality for a reading by the expert gynaecologist. The positive nurse PIA readings were concordant with the positive expert PIA readings in 82% of cases, and the negative PIA readings between the two groups were fully concordant in 89% of cases. These results suggest that mobile telemedicine may be useful to improve access of women in remote areas to cervical cancer screening utilizing the VIA `see-and-treat' method.
PMCID: PMC3746464  PMID: 21551217
12.  Determinants of Excessive Daytime Sleepiness and Fatigue in Adults with Heart Failure 
Clinical nursing research  2011;21(3):271-293.
Little is known about excessive daytime sleepiness (EDS) in heart failure (HF). The aim of this cross-sectional descriptive study was to describe the prevalence of EDS and factors associated with it in HF. A secondary purpose was to explore the correlates of fatigue. We enrolled a consecutive sample of 280 adults with a confirmed diagnosis of chronic HF from three outpatient settings in the northeastern US. Patients with major depressive illness were excluded. Clinical, sociodemographic, behavioral, and perceptual factors were explored as possible correlates of EDS. Using an Epworth Sleepiness Scale score >10, the prevalence of EDS was 23.6%. Significant determinants of EDS were worse sleep quality (p=0.048), worse functional class (p=0.004), not taking a diuretic (p=0.005), and lack of physical activity (p=0.04). Only sleep quality was associated with fatigue (p<0.001). Sleep disordered breathing was not significantly associated with EDS or with fatigue. These factors may be amenable to intervention.
PMCID: PMC3501004  PMID: 21878581
fatigue; physical activity; exercise; diuretics; functional class; excessive daytime sleepiness; heart failure
13.  Double jeopardy: the influence of excessive daytime sleepiness and impaired cognition on health-related quality of life in adults with heart failure 
European Journal of Heart Failure  2012;14(7):730-736.
To determine how excessive daytime sleepiness (EDS) and impaired cognition contribute to health-related quality of life (HRQL) in heart failure (HF).
Methods and results
Adults with chronic HF were enrolled into a prospective cohort study. Data were obtained from 280 subjects enrolled from three sites in the northeastern USA; 242 completed the 6-month study. At baseline, cohorts with and without EDS were identified using the Epworth Sleepiness Scale. Each EDS group was further subdivided into those with and without impaired cognition using a battery of five neuropsychological tests. Two disease-specific measures, the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Functional Outcomes of Sleep Questionnaire (FOSQ), were used to measure HRQL. General linear modelling of square-transformed variables was used to test the hypothesis that cohort membership was a significant predictor of HRQL. At 6 months the remaining sample was 62.5 [standard deviation (SD) 12] years old, mostly male (63%), white (65%), and functionally compromised [72% New York Heart Association (NYHA) class III/IV]. The cohort with both EDS and impaired cognition had the lowest KCCQ overall summary score (60.5 ± 22.5) compared with the cohort without EDS or impaired cognition (74.6 ± 17.4, P ≤ 0.001). A similar effect was seen on the FOSQ (16.0 ± 2.8 vs. 18.5 ± 2.2, P < 0.001).
Impaired cognition alone did not explain poor HRQL, but the addition of EDS poses a significant risk for poor HRQL. Interventions designed to influence EDS may improve HRQL in this population.
PMCID: PMC3380544  PMID: 22510422
Heart failure; Quality of life; Sleep; Cognition
14.  Predictors of Objectively Measured Medication Nonadherence in Adults with Heart Failure 
Circulation. Heart Failure  2012;5(4):430-436.
Medication nonadherence rates are high. The factors predicting nonadherence in heart failure (HF) remain unclear.
Methods and Results
A sample of 202 adults with HF was enrolled from the Northeastern U.S. and followed for 6 months. Specific aims were to describe the types of objectively measured medication nonadherence (e.g. taking, timing, dosing, drug holidays) and to identify contributors to nonadherence 6 months after enrollment. Latent growth mixture modeling (GMM) was used to identify distinct trajectories of adherence. Indicators of the five World Health Organization (WHO) dimensions of adherence (socioeconomic, condition, therapy, patient, and health care system) were tested to identify contributors to nonadherence. Two distinct trajectories were identified and labeled persistent adherence (77.8%) and steep decline (22.3%). Three contributors to the steep decline in adherence were identified. Participants with lapses in attention (adjusted odds ratio (OR) = 2.65, p=0.023), those with excessive daytime sleepiness (OR = 2.51, p=0.037), and those with two or more medication dosings per day (OR = 2.59, p=0.016) were more likely to have a steep decline in adherence over time than to have persistent adherence.
Two distinct patterns of adherence were identified. Three potentially modifiable contributors to nonadherence have been identified.
PMCID: PMC3405361  PMID: 22647773
heart failure; medication adherence; patient compliance; self-care; sleep; World Health Organization
15.  Recent and Past Intimate Partner Abuse and HIV Risk Among Young Women 
To examine the associations between past intimate partner abuse experienced during adolescence (verbal and physical), recent intimate partner abuse (verbal, physical, and sexual), and HIV risk (as indicated by lack of condom use) for sexually active young adult women in relationships with male partners.
Secondary data analysis of waves II and III of the National Longitudinal Study of Adolescent Health (Add Health).
The Add Health Study is a longitudinal, in-home survey of a nationally representative sample of adolescents.
Analyses involved 2,058 sexually active young adult women.
Main Outcome Measures
HIV risk was measured by consistent condom use over the past 12 months.
Physical and verbal abuse experienced in adolescence were associated with physical/verbal abuse experienced in young adulthood. Young, sexually active women experiencing no abuse in their relationships were more likely to consistently use condoms in the past 12 months than were their abused counterparts.
A causal pathway may exist between prior abuse, current abuse, and HIV risk.
PMCID: PMC3677848  PMID: 18336447
HIV; adolescent; risk taking; intimate partner violence; dating violence; sexually transmitted diseases
16.  Parent–Adolescent Communication About Sexual Pressure, Maternal Norms About Relationship Power, and STI/HIV Protective Behaviors of Minority Urban Girls 
Racial/ethnic minority adolescent girls bear a disproportionate risk for HIV and face barriers to autonomous sexual decision making, but parental messages may help protect against sexual risk taking. The authors examined African American and Hispanic girls’ sexually transmitted infection (STI) and HIV prevention practices, parent–adolescent communication about sexual pressure, and maternal gender norms (N = 118). Teens were more likely to practice consistent STI/HIV prevention when mothers talked about partner sexual pressure (p = .017) and fathers talked about resisting partner sexual pressure (p = .034). Sexually active girls who perceived that their mothers held egalitarian beliefs about partner decision making had more consistent condom use (p = .029). Given the context of increased STI/HIV risk, it is critical that parents discuss partner dynamics with daughters. Nurses play a unique role in facilitating these conversations; they provide parents with age-appropriate resources and assist in normalizing fears, which can help increase parent–child sexual-risk communication.
PMCID: PMC3677849  PMID: 21672881
parent–adolescent communication; sexual decision making; sexual pressure; partner relationships; sexual risk; adolescent females; HIV prevention
17.  Sexual Relationship Power, Intimate Partner Violence, and Condom Use Among Minority Urban Girls 
Journal of interpersonal violence  2008;23(12):1694-1712.
This study examined the association between sexual relationship power, intimate partner violence, and condom use among African American and Hispanic urban girls. In this sample of 56 sexually active girls, 50% did not use condoms consistently and therefore were at higher risk for acquiring HIV or sexually transmitted diseases (STDs). Teens who experienced more intimate partner violence had a significantly higher likelihood of inconsistent condom use and therefore a greater risk for HIV/STDs. Girls' sense of sexual control in their relationships was not directly associated with inconsistent condom use but was inversely related to verbal and emotional abuse. Interventions aimed at reducing HIV/STD risk for adolescent girls need to address patterns of dominance and control in adolescent relationships as well as multiple forms of partner violence. This suggests the need for multilevel intervention approaches that promote girls' agency and multiple ways to keep girls safe from perpetrators of partner abuse.
PMCID: PMC3677854  PMID: 18349344
adolescents; prevention; condom use; partner abuse; relationship power; intimate partner violence
18.  The Epidemiology of Intensive Care Unit Readmissions in the United States 
Rationale: The incidence of intensive care unit (ICU) readmissions across the United States is unknown.
Objectives: To determine incidence of ICU readmissions in United States hospitals, and describe the distribution of time between ICU discharges and readmissions.
Methods: This retrospective cohort study used 196,202 patients in 156 medical and surgical ICUs in 106 community and academic hospitals participating in Project IMPACT from April 1, 2001, to December 31, 2007. We used mixed-effects logistic regression, adjusting for patient and hospital characteristics, to describe how ICU readmission rates differed across patient types, ICU models, and hospital types.
Measurements and Main Results: Measurements consisted of 48- and 120-hour ICU readmission rates and time to readmission. A total of 3,905 patients (2%) were readmitted to the ICU within 48 hours, and 7,171 (3.7%) within 120 hours. In adjusted analysis, there was no difference in ICU readmissions across patient types or ICU models. Among medical patients, those in academic hospitals had higher odds of 48- and 120-hour readmission than patients in community hospitals without residents (1.51 [95% confidence interval, 1.12–2.02] and 1.63 [95% confidence interval, 1.24–2.16]). Median time to ICU readmission was 3.07 days (interquartile range, 1.27–6.58). Closed ICUs had the longest times to readmission (3.55 d [interquartile range, 1.42–7.50]).
Conclusions: Approximately 2% and 4% of ICU patients discharged to the ward are readmitted within 48 and 120 hours, within a median time of 3 days. Medical patients in academic hospitals are more likely to be readmitted than patients in community hospitals without residents. ICU readmission rates could be useful for policy makers and investigations into their causes and consequences.
PMCID: PMC3359937  PMID: 22281829
ICU readmissions; quality indicators; hospital trends
19.  Posterior leaflet augmentation improves leaflet tethering in repair of ischemic mitral regurgitation☆,☆☆ 
Objectives: Ischemic mitral regurgitation results from annular dilatation, leaflet tethering and leaflet flattening. Undersized annuloplasty corrects annular dilatation but worsens leaflet tethering and flattening. This exacerbation of abnormal leaflet geometry may contribute to poor repair results for ischemic mitral regurgitation (IMR). Using a sheep model of IMR, we hypothesized that posterior leaflet augmentation and less-extreme annular undersizing would relieve tethering and increase leaflet curvature. Methods: Eight weeks after posterolateral infarct, 10 sheep with ≥2+ IMR underwent either a 24-mm planar ring annuloplasty (n = 5) or a 30-mm planar ring annuloplasty with concomitant posterior leaflet augmentation (n = 5). Real-time three-dimensional echocardiography allowed measurement of indices of leaflet curvature and tethering before and after annuloplasty. Results: Comparing pre- and post-repair values in the P1, P2, and P3 leaflet regions, undersized 24-mm ring annuloplasty made no significant difference to mean septolateral curvature (0.23–0.26, 0.33–0.29, and 0.27–0.37 cm−1, respectively), whereas leaflet augmentation in combination with a 30-mm ring annuloplasty increased septolateral curvature (P1 0.30–1.02, P2 0.31–1.23, and P3 0.35–0.84 cm−1, p-values ≪ 0.05). The mean tethering angle formed between the annular plane and the posterior leaflet increased in all three posterior regions for the 24-mm ring group (P1 12–23°, P2 26–31°, and P3 16–25°), but decreased in all regions for the group undergoing leaflet augmentation (P1 +5 to −6°, P2 +13 to −13°, P3 +16-15°, all p-values ≪ 0.05). Conclusions: Undersized annuloplasty exacerbates leaflet tethering. Posterior leaflet augmentation with less severe annular reduction increases leaflet curvature and decreases tethering; this technique more completely addresses the pathogenic mechanism of IMR and may improve repair durability.
PMCID: PMC3598376  PMID: 21546260
Echocardiography; Mitral regurgitation; Mitral valve repair; Myocardial infarction; Posterior leaflet
20.  Ovarian Stimulation and Low Birth Weight in Infants Conceived Through In Vitro Fertilization 
Obstetrics and gynecology  2011;118(4):863-871.
Singleton infants born after in-vitro fertilization (IVF) are at increased risk for low birth weight (LBW) and/or preterm delivery. We sought to assess if the alteration of the peri-implantation maternal environment due to ovarian stimulation may contribute to increased risk in in vitro fertilization (IVF) births.
The Society of Assisted Reproductive Technology database was used to identify IVF-conceived infants born in the United States between 2004-2006. Associations were assessed in infants born after fresh compared with frozen and thawed embryo transfer in women of similar ovarian responsiveness, in paired analysis of infants born to the same woman following both types of embryo transfer, and in infants born following oocyte donation.
Of 56,792 infants identified, 38,626 and 18,166 were conceived following transfer of fresh and frozen embryos, respectively. In singletons, there was no difference in preterm delivery. However, the odds of overall low birth weight (LBW) (10% vs.7.2%; AOR 1.35, 95% CI 1.20-1.51), LBW at term (2.5% vs. 1.2%; AOR 1.73, 95% CI 1.31-2.29), and preterm LBW (34.1% vs. 23.8%; AOR 1.49, 95% CI 1.24-1.78) were all significantly higher following fresh embryo transfer. In singletons following either fresh or frozen embryo transfer in the same patient, this association was even stronger (LBW: [11.5% vs. 5.6%; AOR 4.66, 95% CI 1.18 – 18.38,). In oocyte donor recipients who do not undergo any ovarian hormonal stimulation for either a fresh or a frozen embryo transfer, no difference in LBW was demonstrated (11.5% vs.11.3%; AOR 0.99, 95% CI 0.82 – 1.18).
The ovarian stimulation-induced maternal environment appears to represent an independent mediator contributing to the risk of LBW, but not preterm delivery, in infants conceived following IVF.
PMCID: PMC3178887  PMID: 21934450
21.  The Effect of Insurance Status on Mortality and Procedural Use in Critically Ill Patients 
Rationale: Lack of health insurance may be an independent risk factor for mortality and differential treatment in critical illness.
Objectives: To determine whether uninsured critically ill patients had differences in 30-day mortality and critical care service use compared with those with private insurance and to determine if outcome variability could be attributed to patient-level or hospital-level effects.
Methods: Retrospective cohort study using Pennsylvania hospital discharge data with detailed clinical risk adjustment, from fiscal years 2005 and 2006, consisting of 167 general acute care hospitals, with 138,720 critically ill adult patients 64 years of age or younger.
Measurements and Main Results: Measurements were 30-day mortality and receipt of five critical care procedures. Uninsured patients had an absolute 30-day mortality of 5.7%, compared with 4.6% for those with private insurance and 6.4% for those with Medicaid. Increased 30-day mortality among uninsured patients persisted after adjustment for patient characteristics (odds ratio [OR], 1.25 for uninsured vs. insured; 95% confidence interval [CI], 1.04–1.50) and hospital-level effects (OR, 1.26; 95% CI, 1.05–1.51). Compared with insured patients, uninsured patients had decreased risk-adjusted odds of receiving a central venous catheter (OR, 0.84; 95% CI, 0.72–0.97), acute hemodialysis (OR, 0.59; 95% CI, 0.39–0.91), and tracheostomy (OR, 0.43; 95% CI, 0.29–0.64).
Conclusions: Lack of health insurance is associated with increased 30-day mortality and decreased use of common procedures for the critically ill in Pennsylvania. Differences were not attributable to hospital-level effects, suggesting that the uninsured have a higher mortality and receive fewer procedures when compared with privately insured patients treated at the same hospitals.
PMCID: PMC3208649  PMID: 21700910
insurance; intensive care unit; critical care; mortality
22.  Vitamin D Deficiency is Associated with Type 2 Diabetes Mellitus in HIV Infection 
AIDS (London, England)  2011;25(4):525-529.
Metabolic complications, including type 2 diabetes mellitus (DM) and metabolic syndrome, are increasingly recognized among HIV-infected individuals. Low vitamin D levels increase the risk of type 2 DM, and vitamin D supplementation has been shown to decrease the risk of type 2 DM in patients without HIV infection.
The primary objective was to determine whether vitamin D deficiency (serum 25-hyrdoxyvitamin D<20 ng/mL) was associated with type 2 DM among HIV-infected patients. Our secondary objective was to determine whether vitamin D deficiency was associated with metabolic syndrome in HIV.
We conducted a cross-sectional study among subjects enrolled in the prospective Modena (Italy) HIV Metabolic Clinic Cohort. Clinical and laboratory data, including history of type 2 DM, fasting blood glucose, components of metabolic syndrome, and 25-hydroxyvitamin D levels, were obtained for all subjects.
After adjusting for vitamin D supplementation, sex, age, body mass index, and hepatitis C virus co-infection, vitamin D deficiency was associated with type 2 DM (adjusted OR, 1.85; 95% CI, 1.03–3.32; p=.038). The association between vitamin D deficiency and metabolic syndrome was not significant after adjusting for vitamin D supplementation, sex age and body mass index (adjusted OR 1.32; 95% CI, 1.00–1.75;p=.053).
Our study demonstrates an association between vitamin D deficiency and type 2 DM. Clinical trials are needed to better characterize the association between vitamin D deficiency and type 2 DM in HIV infection and to evaluate whether vitamin D is able to prevent or delay the onset of type 2 DM.
PMCID: PMC3366629  PMID: 21178753
vitamin D deficiency; type 2 DM; insulin resistance; metabolic syndrome
23.  Relationships Between Physical and Non-Physical Forms of Intimate Partner Violence and Depression among Urban Minority Adolescent Females 
Little is known about intimate partner violence (IPV) and depression among low income, urban African American and Hispanic adolescent females.
Interviews with 102 urban African American and Hispanic adolescent females examined physical abuse, emotional/verbal abuse, and threats, and their unique and combined associations with depression.
One-quarter of the sample experienced all three types of abuse. Non-physical forms of IPV were significantly associated with depression.
Some urban adolescent females from lower income households experience high rates of IPV. Physical and non-physical forms of IPV are important in understanding and responding to depression in this population.
PMCID: PMC3100197  PMID: 21617762
Violence; depression; adolescence
24.  Excessive Daytime Sleepiness is Associated with Poor Medication Adherence in Adults with Heart Failure 
Journal of cardiac failure  2010;17(4):340-348.
A relationship between excessive daytime sleepiness (EDS) and poor treatment adherence has been suspected but not confirmed. We hypothesized that medication adherence would be poorer in adults with heart failure (HF) and EDS and that cognitive status would be the mechanism of effect.
A sample of 280 adults with chronic HF was enrolled into a prospective cohort comparison study. We identified a cohort with EDS and a control group without EDS and further divided both groups into those with and without mild cognitive decline. Data on medication adherence was obtained at baseline, 3- and 6-months using the Basel Assessment of Adherence Scale (BAASIS). Regression analysis was used to clarify the contribution of EDS and cognition to medication adherence and to assess relationships over six months after adjusting for age, enrollment site, gender, race, functional class, depression, and premorbid intellect.
At baseline, 62% of subjects were nonadherent to their medication regime. Nonadherence was significantly more common in those with EDS, regardless of cognitive status (p=0.035). The odds of nonadherence increased by 11% for each unit increase in EDS (AOR=1.11, 95% CI=1.05–1.19, p=0.001). In longitudinal models there was a 10% increase in the odds of nonadherence for each unit increase in EDS (p=0.008). The only cognition measure significantly associated with medication adherence was attention (p=0.047).
Adults with HF and EDS are more likely to have problems adhering to their medication regimen than those without EDS, regardless of their cognitive status. Identifying and correcting factors that interfere with sleep may improve medication adherence.
PMCID: PMC3073685  PMID: 21440873
heart failure; sleep; excessive daytime sleepiness; cognition; vigilance; patient compliance; self-care
25.  Acute Anemia Elicits Cognitive Dysfunction and Evidence of Cerebral Cellular Hypoxia in Older Rats with Systemic Hypertension 
Anesthesiology  2010;113(4):845-858.
Postoperative cognitive dysfunction occurs frequently after cardiac, major vascular, and major orthopedic surgery. Aging and hypertensive cerebrovascular disease are leading risk factors for this disorder. Acute anemia, common to major surgery, has been identified as a possible contributor to postoperative cognitive dysfunction. The effect of hypoxia upon cognition and the cellular and molecular processes involved in learning and memory has been well described. Cerebrovascular changes related to chronic hypertension may expose cells to increased hypoxia with anemia.
Young to aged spontaneously hypertensive rats underwent testing for visuospatial memory and learning in the Morris water maze, measurement of cerebral tissue oxygenation via tissue oxygen probe, and measurement of hypoxia-sensitive genes and proteins, under conditions of sham and experimental isovolemic anemia.
Acute isovolemic anemia elicited evidence of aging-dependent visuospatial working memory and learning impairment. Isovolemic anemia did not result in cerebral tissue hypoxia, when measured via tissue oxygen probe. Evidence of cellular hypoxia was, however, identified in response to the anemic challenge, as hypoxia-sensitive genes and proteins were up-regulated. Importantly, cellular hypoxic gene responses were increased with anemia in an age-dependent manner in this model of aging with chronic hypertension.
In a translational model of chronic hypertension, clinically relevant levels of acute anemia were associated with an age-dependent visuospatial working memory and learning impairment that was matched by an age-dependent cellular sensitivity to anemic hypoxia. These data offer support for a possible link between anemic hypoxia and postoperative cognitive dysfunction in humans.
PMCID: PMC3233697  PMID: 20808217

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