Publications by authors named "Dina Appleby"

22 Publications

  • Page 1 of 1

Comparison of deep phenotyping features of UCPPS with and without Hunner lesion: A MAPP-II Research Network Study.

Neurourol Urodyn 2021 03 19;40(3):810-818. Epub 2021 Feb 19.

Department of Urology, University of Michigan, Ann Arbor, Michigan, USA.

Objective: To use the phenotyping data from the MAPP-II Symptom Patterns Study (SPS) to compare the systemic features between urologic chronic pelvic pain syndrome (UCPPS) with Hunner lesion (HL) versus those without HL.

Methods: We performed chart review on 385 women and 193 men with UCPPS who enrolled in the MAPP-II SPS. 223 had cystoscopy and documentation of HL status. Among them, 12.5% had HL and 87.5% did not.

Results: UCPPS participants with HL were older, had increased nocturia, higher Interstitial Cystitis Symptom and Problem Indexes, and were more likely to report "painful urgency" compared with those without HL. On the other hand, UCPPS without HL reported more intense nonurologic pain, greater distribution of pain outside the pelvis, greater numbers of comorbid chronic overlapping pain conditions, higher fibromyalgia-like symptoms, and greater pain centralization, and were more likely to have migraine headache than those with HL. UCPPS without HL also had higher anxiety, perceived stress, and pain catastrophizing than those with HL. There were no differences in sex distribution, UCPPS symptom duration, intensity of urologic pain, distribution of genital pain, pelvic floor tenderness on pelvic examination, quality of life, depression, pain characteristics (nociceptive pain vs. neuropathic pain), mechanical hypersensitivity in the suprapubic area during quantitative sensory testing, and 3-year longitudinal pain outcome and urinary outcome between the two groups.

Conclusions: UCPPS with HL displayed more bladder-centric symptom profiles, while UCPPS without HL displayed symptoms suggesting a more systemic pain syndrome. The MAPP-II SPS phenotyping data showed that Hunner lesion is a distinct phenotype from non-Hunner lesion.
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http://dx.doi.org/10.1002/nau.24623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159180PMC
March 2021

Posttraumatic Symptom Reporting and Reported Cigarette Smoking During Pregnancy.

J Womens Health (Larchmt) 2017 06 21;26(6):662-669. Epub 2017 Feb 21.

2 Department of Obstetrics and Gynecology, Perelman School of Medicine at the University of Pennsylvania , Philadelphia, Pennsylvania.

Introduction: Increased prevalence of nicotine dependence among individuals suffering from posttraumatic stress disorder (PTSD) is well established. However, there are limited studies on the prevalence of smoking during pregnancy in relation to prepregnancy history of trauma exposures and active PTSD symptoms during pregnancy. Prenatal smoking has been implicated in a host of negative outcomes for mother and baby. Given maternal and fetal risk, it is critical to define predictors of continued cigarette smoking during pregnancy.

Methods: Pregnant women from an urban perinatal clinic completed an anonymous survey of trauma history using a modified Traumatic Life Events Questionnaire (TLEQ), PTSD symptoms using the PTSD Symptom Checklist-Civilian Version (PCL-C) and current and past smoking behavior. Those who smoked any number of cigarettes per day after pregnancy confirmation were considered to be "pregnant smokers."

Results: Of 218 women who completed the survey, 34 (15.6%) reported smoking cigarettes after confirmation of pregnancy. In unadjusted models, trauma exposure that resulted in fear, helplessness, or horror (FHH), as well as current PTSD symptom severity and probable PTSD diagnosis showed statistical significance as predictors of smoking during pregnancy. After adjusting for age only, PTSD symptoms retained their significant association with smoking during pregnancy. When history of smoking at least five cigarettes per day was added to our models, none of the associations remained significant.

Conclusions: These findings emphasize the importance of the behavioral response to past traumatic exposures in influencing cigarette smoking behavior before pregnancy. Given such behaviors enhance risk for continued tobacco use during pregnancy, a trauma-informed approach to smoking cessation in preconception care may ultimately reduce the likelihood of smoking during pregnancy and requires further study.
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http://dx.doi.org/10.1089/jwh.2016.5928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512338PMC
June 2017

Movement patterns in women at risk for perinatal depression: use of a mood-monitoring mobile application in pregnancy.

J Am Med Inform Assoc 2017 Jul;24(4):746-753

Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Objectives: To examine, using a smartphone application, whether mood is related to daily movement patterns in pregnant women at risk for perinatal depression.

Materials And Methods: Thirty-six women with elevated depression symptoms (PHQ-9 ≥ 5) in pregnancy used the application for 8 weeks. Mood was reported using application-administered surveys daily (2 questions) and weekly (PHQ-9 and GAD-7). The application measured daily mobility (distance travelled on foot) and travel radius. Generalized linear mixed-effects regression models estimated the association between mood and movement.

Results: Women with milder depression symptoms had a larger daily radius of travel (2.7 miles) than women with more severe symptoms (1.9 miles), P  = .04. There was no difference in mobility. A worsening of mood from the prior day was associated with a contracted radius of travel, as was being in the group with more severe symptoms. No significant relationships were found between anxiety and either mobility or radius.

Discussion: We found that the association of mood with radius of travel was more pronounced than its association with mobility. Our study also demonstrated that a change in mood from the prior day was significantly associated with radius but not mood on the same day that mobility and radius were measured.

Conclusion: This study lays the groundwork for future research on how smartphone mood-monitoring applications can combine actively and passively collected data to better understand the relationship between the symptoms of perinatal depression and physical activity that could lead to improved monitoring and novel interventions.
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http://dx.doi.org/10.1093/jamia/ocx005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580935PMC
July 2017

Methodology for Using 3-Dimensional Sonography to Measure Fetal Adrenal Gland Volumes in Pregnant Women With and Without Early Life Stress.

J Ultrasound Med 2016 Sep 25;35(9):2029-37. Epub 2016 Aug 25.

Department of Obstetrics and Gynecology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania USA.

Fetal adrenal gland volumes on 3-dimensional sonography have been studied as potential predictors of preterm birth. However, no consistent methodology has been published. This article describes the methodology used in a study that is evaluating the effects of maternal early life stress on fetal adrenal growth to allow other researchers to compare methodologies across studies. Fetal volumetric data were obtained in 36 women at 20 to 22 and 28 to 30 weeks' gestation. Two independent examiners measured multiple images of a single fetal adrenal gland from each sonogram. Intra- and inter-rater consistency was examined. In addition, fetal adrenal volumes between male and female fetuses were reported. The intra- and inter-rater reliability was satisfactory when the mean of 3 measurements from each rater was used. At 20 weeks' gestation, male fetuses had larger average adjusted adrenal volumes than female fetuses (mean, 0.897 versus 0.638; P = .004). At 28 weeks' gestation, the fetal weight was more influential in determining values for adjusted fetal adrenal volume (0.672 for male fetuses versus 0.526 for female fetuses; P = .034). This article presents a methodology for assessing fetal adrenal volume using 3-dimensional sonography that can be used by other researchers to provide more consistency across studies.
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http://dx.doi.org/10.7863/ultra.15.10046DOI Listing
September 2016

Lisdexamfetamine Effects on Executive Activation and Neurochemistry in Menopausal Women with Executive Function Difficulties.

Neuropsychopharmacology 2017 01 23;42(2):437-445. Epub 2016 Aug 23.

Department of Psychiatry, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA, USA.

Many women with no history of executive dysfunction report difficulties in this domain during the menopause transition. Lisdexamfetamine (LDX) has been suggested to be a safe and effective treatment option for these women. However, the mechanism by which LDX improves executive functioning in these women is not known. Here we investigated the effects of LDX on brain activation and neurochemistry, hypothesizing that LDX would be associated with increased activation and decreased glutamate in executive regions. Fourteen women underwent multimodal neuroimaging at 7T at three time points in this baseline-corrected, double-blind, placebo-controlled, crossover study. Effects of LDX on symptom severity, blood-oxygen-level-dependent (BOLD) signal, and dorsolateral prefrontal cortex (DLPFC) glutamate+glutamine (Glx) were measured using a clinician-administered questionnaire, fMRI during performance of a fractal n-back task, and H-MRS, respectively. The effect of treatment (LDX minus baseline vs placebo minus baseline) on these behavioral and neural markers of executive function was examined using repeated measures mixed effects models. LDX treatment was associated with decreased symptom severity, increased activation in the insula and DLPFC, and decreased DLPFC Glx. In addition, the magnitude of LDX-induced improvement in symptom severity predicted both direction and magnitude of LDX-induced change in insular and DLPFC activation. Moreover, symptom severity was positively correlated with Glx concentration in the left DLPFC at baseline. These findings provide novel evidence that the neural mechanisms by which LDX acts to improve self-reported executive functioning in healthy menopausal women with midlife onset of executive difficulties include modulation of insular and DLPFC recruitment as well as decrease in DLPFC Glx concentration.
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http://dx.doi.org/10.1038/npp.2016.162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399233PMC
January 2017

A randomized controlled trial of negative co-payments: the CHORD trial.

Am J Manag Care 2015 Aug;21(8):e465-73

Center for Health Equity Research & Promotion, Philadelphia Veterans Affairs Medical Center, PA

Objectives: Value-based insurance designs are being widely used. We undertook this study to examine whether a financial incentive that lowered co-payments for blood pressure medications below $0 improved blood pressure control among patients with poorly controlled hypertension.

Study Design: Randomized controlled trial.

Methods: Participants from 3 Pennsylvania hospitals (n = 337) were randomly assigned to: a) be paid $8 per medication per month for filling blood pressure prescriptions, b) a computerized behavioral intervention (CBI), c) both payment and CBI, or d) usual care. The primary outcome was change in blood pressure between baseline and 12 months post enrollment. We also measured adherence using the medication possession ratio in a subset of participants.

Results: There were no significant interactions between the incentive and the CBI interventions. There were no significant changes in medication possession ratio in the treatment group. Blood pressure decreased among all participants, but to a similar degree between the financial incentive and control groups. Systolic blood pressure (SBP) dropped 13.7 mm Hg for the incentive group versus 10.0 mm Hg for the control group (difference = –3.7; 95% CI, –9.0 to 1.6; P = .17). The proportion of patients with blood pressure under control 12 months post enrollment was 35.6% of the incentive group versus 27.7% of the control group (odds ratio, 1.4; 95% CI, 0.8-2.5; P = .19). Diabetics in the incentive group had an average drop in SBP of 12.7 mm Hg between baseline and 12 months compared with 4.0 mm Hg in the control group (P = .02). Patients in the incentive group without diabetes experienced average SBP reductions of 15.0 mm Hg, compared with 16.3 mm Hg for control group nondiabetics (P = .71).

Conclusions: Among patients with poorly controlled blood pressure, financial incentives—as implemented in this trial—did not improve blood pressure control or adherence except among patients with diabetes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171502PMC
August 2015

A randomized controlled trial of co-payment elimination: the CHORD trial.

Am J Manag Care 2015 Aug;21(8):e455-64

Center for Health Equity Research & Promotion, Philadelphia Veterans Affairs Medical Center, PA

Objectives: Efforts to improve adherence by reducing co-payments through value-based insurance design are become more prevalent despite limited evidence of improved health outcomes. The objective of this study was to determine whether eliminating patient co-payments for blood pressure medications improves blood pressure control.

Study Design: Randomized controlled trial.

Methods: The Collaboration to Reduce Disparities in Hypertension (CHORD) was a randomized controlled trial with 12 months' follow-up conducted among patients from the Philadelphia and Pittsburgh Veterans Administration Medical Centers. We enrolled 479 patients with poorly controlled systolic blood pressure. Participants were randomly assigned to: a) receive reductions in co-payments from $8 to $0 per medication per month for each antihypertensive prescription filled, b) a computerized behavioral intervention (CBI), c) both co-pay reduction and CBI, or d) usual care. Our main outcome measure was change in systolic blood pressure from enrollment to 12 months post enrollment. We also measured adherence using the medication possession ratio in a subset of participants.

Results: There were no significant interactions between the co-payment interventions and the CBI interventions. There was no relative difference in the change in medication possession ratio between baseline and 12 months (0.05% and -.90% in control and incentive groups, respectively; P = .74) or in continuous medication gaps of 30, 60, or 90 days. Blood pressure decreased among all participants, but to a similar degree between the financial incentive and control groups. Systolic pressure within the incentive group dropped 13.2 mm Hg versus 15.2 mm Hg for the control group (difference = 2.0; 95% CI, -2.3 to 6.3; P = .36). The proportion of patients with blood pressure under control at 12 months was 29.5% in the incentive group versus 33.9 in the control group (odds ratio, 0.8; 95% CI, 0.5-1.3; P = .36).

Conclusions: Among patients with poorly controlled blood pressure, financial incentives--as implemented in this trial--that reduced patient cost sharing for blood pressure medications did not improve medication adherence or blood pressure control.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142179PMC
August 2015

New onset executive function difficulties at menopause: a possible role for lisdexamfetamine.

Psychopharmacology (Berl) 2015 Aug 11;232(16):3091-100. Epub 2015 Jun 11.

Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA,

Rationale: Reports of cognitive decline, particularly in the domains of executive functions (EFs), are common among menopausal women.

Objective: This study aims to determine the impact of the psychostimulant lisdexamfetamine (LDX) on subjective and objective cognitive function among menopausal women who report new-onset EF complaints.

Methods: Thirty-two healthy perimenopausal and early postmenopausal women experiencing mid-life-onset executive function difficulties as measured using the Brown Attention Deficit Disorder Scale (BADDS) were administered LDX 40-60 mg/day for 4 weeks in this double-blind, placebo-controlled, cross-over study. Diagnosis of lifetime ADHD was exclusionary. BADDS total and subscale scores and performance on verbal memory and working memory tasks were outcomes of interest.

Results: Analyses revealed a significant effect of LDX treatment over placebo for total BADDS scores (p = 0.0001) and for four out of the five BADDS subscales (all p < 0.004). LDX treatment also resulted in significant improvement in delayed paragraph recall (p = 0.018), but there was no significant effect of treatment on other cognitive measures. Systolic blood pressure (p = 0.017) and heart rate increased significantly (p = 0.006) when women were on LDX but remained, on average, within the normal range.

Conclusions: LDX 40-60 mg/day was well tolerated and improved the subjective measures of executive function as well as objective measures of delayed verbal recall in this sample of healthy menopausal women.
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http://dx.doi.org/10.1007/s00213-015-3953-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631394PMC
August 2015

Placental transfer of antidepressant medications: implications for postnatal adaptation syndrome.

Clin Pharmacokinet 2015 Apr;54(4):359-70

Department of Psychiatry, Penn Center for Women's Behavioral Wellness, Perelman School of Medicine at the University of Pennsylvania, 3535 Market St., 3rd Floor, Philadelphia, PA, 19104, USA,

Seven to thirteen percent of women are either prescribed or taking (depending on the study) an antidepressant during pregnancy. Because antidepressants freely cross into the intrauterine environment, we aim to summarize the current findings on placental transfer of antidepressants. Although generally low risk, antidepressants have been associated with postnatal adaptation syndrome (PNAS). Specifically, we explore whether the antidepressants most closely associated with PNAS (paroxetine, fluoxetine, venlafaxine) cross the placenta to a greater extent than other antidepressants. We review research on antidepressants in the context of placental anatomy, placental transport mechanisms, placental metabolism, pharmacokinetics, as well as non-placental maternal and fetal factors. This provides insight into the complexity involved in understanding how placental transfer of antidepressants may relate to adverse perinatal outcomes. Ultimately, from this data there is no pattern in which PNAS is related to placental transfer of antidepressant medications. In general, there is large interindividual variability for each type of antidepressant. To make the most clinically informed decisions about the use of antidepressants in pregnancy, studies that link maternal, placental and fetal genetic polymorphisms, placental transfer rates and infant outcomes are needed.
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http://dx.doi.org/10.1007/s40262-014-0233-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566926PMC
April 2015

Success of the two-dose methotrexate protocol for treatment of ectopic pregnancy in women with a history of prior ectopic pregnancy.

J Reprod Med 2014 Jul-Aug;59(7-8):379-84

Objective: Women with prior ectopic pregnancy (EP) have an increased failure rate when treated with single-dose methotrexate (MTX) for subsequent EP. We sought to determine whether previous EP remained a risk factor for failure when using the two-dose MTX protocol.

Study Design: Retrospective cohort study of women managed with two-dose MTX. Risk factors for MTX failure were evaluated in univariable analysis and multivariable regression modeling.

Results: A total of 234 women with EP between 1999 and 2009 were studied. Of those, 37 (15.8%) had a prior EP. In univariable analysis, prior EP was associated with a greater than twofold increased risk of MTX failure (RR 2.67, 95% CI 1.20-3.77). Higher hCG levels and ultrasound visualization of EP also increased the risk of MTX failure. In multivariable analysis hCG level remained associated with MTX failure, while prior EP did not (adjusted RR 0.97, 95% CI 0.33-2.82).

Conclusion: Prior EP is not independently associated with MTX failure in women receiving two-dose MTX therapy after controlling for known risk factors.
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September 2014

Race modifies the association between adiposity and inflammation in patients with chronic kidney disease: findings from the chronic renal insufficiency cohort study.

Obesity (Silver Spring) 2014 May 11;22(5):1359-66. Epub 2014 Feb 11.

Division of Renal Disease and Hypertension, The George Washington University, Washington, DC.

Objective: The race-specific association of inflammation with adiposity and muscle mass in subjects with chronic kidney disease (CKD) was examined.

Methods: Plasma concentration of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-6, IL-10, tumor necrosis factor (TNF)-α, TGF-β, high-sensitivity C-reactive protein (hs-CRP), fibrinogen, and serum albumin was measured in 3,939 Chronic Renal Insufficiency Cohort study participants. Bioelectric impedance analysis was used to determine body fat mass (BFM) and fat-free mass (FFM).

Results: Plasma levels of hs-CRP, fibrinogen, IL-1RA, IL-6, and TNF-α increased and serum albumin decreased across the quartiles of body mass index. In multivariable analysis, BFM and FFM were positively associated with hs-CRP, fibrinogen, IL-1β, IL-1RA, and IL-6. One standard deviation (SD) increase in BFM and FFM was associated with 0.36 (95% confidence interval [CI] = 0.33, 0.39) and 0.26 (95% CI = 0.22, 0.30) SD increase in log-transformed hs-CRP, respectively (P < 0.001). Race stratified analysis showed that the association between biomarkers and BFM and FFM differed by race, with Caucasians, demonstrating a stronger association with markers of inflammation than African Americans.

Conclusions: BFA and FFM are positively associated with markers of inflammation in patients with CKD. Race stratified analysis showed that Caucasians have a stronger association with markers of inflammation compared to African Americans.
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http://dx.doi.org/10.1002/oby.20692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4327849PMC
May 2014

Heart rate variability is a predictor of mortality in chronic kidney disease: a report from the CRIC Study.

Am J Nephrol 2013 14;38(6):517-28. Epub 2013 Dec 14.

Division of Renal Diseases and Hypertension, University of Minnesota, Minneapolis, Minn., USA.

Background/aims: Low heart rate variability (HRV) is a risk factor for adverse outcomes in the general population. We aimed to determine the factors associated with HRV and evaluate the association between low HRV and clinical outcomes in patients with chronic kidney disease (CKD).

Methods: A 10-second electrocardiogram was obtained at baseline in the Chronic Renal Insufficiency Cohort (CRIC) Study. HRV was measured by the standard deviation of all R-R intervals (SDNN) and the root mean square of successive differences between R-R intervals (RMSSD).

Results: In 3,245 CRIC participants with available baseline SDNN and RMSSD, lower HRV was associated with older age, lack of exercise, heart failure, elevated phosphorus and hemoglobin A1c, and low estimated glomerular filtration rate. After a median follow-up of 4.2 years, in fully adjusted models, lower HRV was not associated with renal [SDNN: hazard rate, HR = 0.96 (95% confidence interval, CI 0.88-1.05); RMSSD: HR = 0.97 (95% CI 0.88-1.07)] or cardiovascular outcomes [SDNN: HR = 1.02 (95% CI 0.92-1.13); RMSSD: HR = 1.00 (95% CI 0.90-1.10)]. There was a nonlinear relationship between RMSSD and all-cause mortality with increased risk with both low and high RMSSD (p = 0.04).

Conclusions: In a large cohort of patients with CKD, multiple risk factors for renal and cardiovascular diseases were associated with lower HRV. Lower HRV was not associated with increased risk for renal or cardiovascular outcomes, but both low and high RMSSD were associated with increased risk for all-cause mortality. In conclusion, HRV measured by RMSSD may be a novel and independent risk factor for mortality in CKD patients.
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http://dx.doi.org/10.1159/000357200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920657PMC
September 2014

Comparing metabolomic and pathologic biomarkers alone and in combination for discriminating Alzheimer's disease from normal cognitive aging.

Acta Neuropathol Commun 2013 Jun 27;1:28. Epub 2013 Jun 27.

Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.

Background: A critical and as-yet unmet need in Alzheimer disease (AD) research is the development of novel markers that can identify individuals at risk for cognitive decline due to AD. This would aid intervention trials designed to slow the progression of AD by increasing diagnostic certainty, and provide new pathophysiologic clues and potential drug targets.

Results: We used two metabolomics platforms (gas chromatography-time of flight mass spectrometry [GC-TOF] and liquid chromatography LC-ECA array [LC-ECA]) to measure a number of metabolites in cerebrospinal fluid (CSF) from patients with AD dementia and from cognitively normal controls. We used stepwise logistic regression models with cross-validation to assess the ability of metabolite markers to discriminate between clinically diagnosed AD participants and cognitively normal controls and we compared these data with traditional CSF Luminex immunoassay amyloid-β and tau biomarkers. Aβ and tau biomarkers had high accuracy to discriminate cases and controls (testing area under the curve: 0.92). The accuracy of GC-TOF metabolites and LC-ECA metabolites by themselves to discriminate clinical AD participants from controls was high (testing area under the curve: 0.70 and 0.96, respectively).

Conclusions: Our study identified several CSF small-molecule metabolites that discriminated especially well between clinically diagnosed AD and control groups. They appear to be suitable for further confirmatory and validation studies, and show the potential to provide predictive performance for AD.
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http://dx.doi.org/10.1186/2051-5960-1-28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3893491PMC
June 2013

Quality of embryos transferred and progesterone levels are the most important predictors of live birth after fresh embryo transfer: a retrospective cohort study.

J Assist Reprod Genet 2014 Feb 8;31(2):185-94. Epub 2013 Nov 8.

Reproductive Medicine Center, Women and Children's Hospital of Guangdong Province, 13 GuangYuanXi RD, Guangzhou, China, 510000,

Purpose: To identify the independent predictors of live birth following IVF, and to assess the role of cohort-specific parameters, including antral follicle count (AFC), the number of oocytes retrieved, the total number of embryos, and the total number of good-quality embryos, in fresh IVF cycles.

Methods: A retrospective cohort study of 2,525 infertile women undergoing IVF between 2002 and 2007. The hypothesis that the number and quality of embryos transferred capture the effects previously attributed to cohort-specific variables was examined using mediation analysis and spline analysis. Independent predictors were identified by a bootstrap algorithm. Multivariable logistic regression was performed and the proportion of explained variation was measured to compare the relative importance of transfer-specific vs. cohort-specific predictors.

Results: The number of good-quality embryos transferred and progesterone level on the day of hCG administration ranked as the two most important predictors of live birth. Prospects of pregnancy started to decrease after progesterone level exceeded 0.6 ng/ml. The achievement of live birth in a fresh IVF cycle is primarily determined by the number and quality of embryos transferred, rather than by embryo cohort-specific variables.

Conclusions: The associations between cohort-specific variables and live birth in a fresh IVF cycle are completely mediated by the quality of embryos transferred. Progesterone level on the day of hCG administration is an independent predictor of pregnancy and merits further investigation.
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http://dx.doi.org/10.1007/s10815-013-0129-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933599PMC
February 2014

Comparative survey of the topographical distribution of signature molecular lesions in major neurodegenerative diseases.

J Comp Neurol 2013 Dec;521(18):4339-55

Penn Memory Center, Departments of Psychiatry and Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, 19104.

An understanding of the anatomic distributions of major neurodegenerative disease lesions is important to appreciate the differential clinical profiles of these disorders and to serve as neuropathological standards for emerging molecular neuroimaging methods. To address these issues, here we present a comparative survey of the topographical distribution of the defining molecular neuropathological lesions among 10 neurodegenerative diseases from a large and uniformly assessed brain collection. Ratings of pathological severity in 16 brain regions from 671 cases with diverse neurodegenerative diseases are summarized and analyzed. These include: 1) amyloid-β and tau lesions in Alzheimer's disease; 2) tau lesions in three other tauopathies including Pick's disease, progressive supranuclear palsy and corticobasal degeneration; 3) α-synuclein inclusion ratings in four synucleinopathies including Parkinson's disease, Parkinson's disease with dementia, dementia with Lewy bodies, and multiple system atrophy; and 4) TDP-43 lesions in two TDP-43 proteinopathies, including frontotemporal lobar degeneration associated with TDP-43 and amyotrophic lateral sclerosis. The data presented graphically and topographically confirm and extend previous pathological anatomic descriptions and statistical comparisons highlight the lesion distributions that either overlap or distinguish the diseases in each molecular disease category.
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http://dx.doi.org/10.1002/cne.23430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3872132PMC
December 2013

Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease.

Kidney Int 2011 Jun 9;79(12):1370-8. Epub 2011 Mar 9.

Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.

Fibroblast growth factor 23 (FGF23) regulates phosphorus metabolism and is a strong predictor of mortality in dialysis patients. FGF23 is thought to be an early biomarker of disordered phosphorus metabolism in the initial stages of chronic kidney disease (CKD). We measured FGF23 in baseline samples from 3879 patients in the Chronic Renal Insufficiency Cohort study, which is a diverse cohort of patients with CKD stage 2-4. Mean serum phosphate and median parathyroid hormone (PTH) levels were in the normal range, but median FGF23 was markedly greater than in healthy populations, and increased significantly with decreasing estimated glomerular filtration rate (eGFR). High levels of FGF23, defined as being above 100 RU/ml, were more common than secondary hyperparathyroidism and hyperphosphatemia in all strata of eGFR. The threshold of eGFR at which the slope of FGF23 increased was significantly higher than the corresponding threshold for PTH based on non-overlapping 95% confidence intervals. Thus, increased FGF23 is a common manifestation of CKD that develops earlier than increased phosphate or PTH. Hence, FGF23 measurements may be a sensitive early biomarker of disordered phosphorus metabolism in patients with CKD and normal serum phosphate levels.
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http://dx.doi.org/10.1038/ki.2011.47DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3134393PMC
June 2011

Utility of dilation and curettage in the diagnosis of pregnancy of unknown location.

Am J Obstet Gynecol 2011 Feb;204(2):130.e1-6

Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Objective: We sought to determine utility of uterine evacuation for diagnosis of nonviable pregnancy of unknown location (PUL).

Study Design: We conducted a cohort study to assess the prevalence of ectopic pregnancy (EP), overall, and stratified by presenting signs and symptoms in women with a nonviable PUL.

Results: Of the 173 women, 66 (38%) had miscarriage (spontaneous abortion [SAB]) and 107 (62%) had EP. When initial human chorionic gonadotropin (hCG) was <2000 mIU/mL, the odds of an EP were greater (odds ratio, 4.32; 95% confidence interval, 2.04-9.12). Demographic factors, obstetric history, and clinical presentation were not useful in distinguishing between EP and SAB. Pre-evacuation hCG increase had strong trend association with EP (odds ratio, 2.14; 95% confidence interval, 0.98-4.68). A >30% fall in postcurettage hCG was suggestive, but was not a diagnostic indicator of SAB.

Conclusion: Uterine evacuation is a useful diagnostic aid for women with nonviable PUL. Nondiagnostic ultrasound findings and absolute and serial hCG values are associated with, but do not accurately predict final diagnosis.
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http://dx.doi.org/10.1016/j.ajog.2010.11.021DOI Listing
February 2011

Clinical factors affecting the accuracy of ultrasonography in symptomatic first-trimester pregnancy.

Obstet Gynecol 2011 Feb;117(2 Pt 1):299-306

From the Departments of Obstetrics and Gynecology and Emergency Medicine, Center for Clinical Epidemiology and Biostatistics, Philadelphia, Pennsylvania.

Objective: To evaluate factors associated with accuracy of initial ultrasonography in patients with symptomatic first-trimester pregnancy.

Methods: Ultrasound diagnosis in the emergency department was compared with an ultimate clinical diagnosis in women in need of a gynecologic consult. The sensitivity, specificity, positive predictive values, and accuracy of the initial ultrasound impression were calculated and stratified by criteria of diagnosis, serum human chorionic gonadotropin (hCG) levels, pain, and bleeding.

Results: Eighteen hundred eighty women were evaluated. Overall accuracy of initial ultrasound diagnosis was 78%. A probable ultrasound diagnosis of ectopic pregnancy (adnexal mass without the presence of a yolk sac or embryo) resulted in a higher sensitivity (42.1% compared with 13.2%: P<.001) but a lower positive predictive value (82.7% compared with 98%: P<.01) compared with a definite diagnosis. A probable ultrasound diagnosis of intrauterine pregnancy (double decidual sign without yolk sac or embryo) resulted in a higher sensitivity (36.0% compared with 4.0%; P<.001) and lower positive predictive value (58.8% compared with 87.0%; P>.001) compared with a definite diagnosis. The sensitivity (34.3% compared with 75.9%; P<.01) and positive predictive value (80.4% compared with 91.5%; P=.02) were lower for diagnosis of ectopic pregnancy when serum hCG level was less than 2,000 milli-international units/mL. Ultrasonography was less accurate when bleeding was the chief complaint (72.7% compared with 84.8% P<.006) but not substantially altered by pain as a chief complaint (78.0 compared with 77.8% P>.99).

Conclusion: A substantial number of misdiagnoses can occur when initial ultrasound diagnosis of intrauterine pregnancy or ectopic pregnancy is made without evidence of a yolk sac or embryo, when hCG values are low, or when a patient has significant bleeding.

Level Of Evidence: II.
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http://dx.doi.org/10.1097/AOG.0b013e3182050ed0DOI Listing
February 2011

Long-term acute care hospital utilization after critical illness.

JAMA 2010 Jun;303(22):2253-9

Division of Pulmonary, Allergy, and Critical Care, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Blockley Hall 723, 423 Guardian Dr, Philadelphia, PA 19104, USA.

Context: Long-term acute care hospitals have emerged as a novel approach for the care of patients recovering from severe acute illness, but the extent and increases in their activity at the national level are unknown.

Objective: To examine temporal trends in long-term acute care hospital utilization after an episode of critical illness among fee-for-service Medicare beneficiaries aged 65 years or older.

Design, Setting, And Patients: Retrospective cohort study using the Medicare Provider Analysis and Review files from 1997 to 2006. We included all Medicare hospitalizations involving admission to an intensive care unit of an acute care, nonfederal hospital within the continental United States.

Main Outcome Measures: Overall long-term acute care utilization, associated costs, and survival following transfer.

Results: The number of long-term acute care hospitals in the United States increased at a mean rate of 8.8% per year, from 192 in 1997 to 408 in 2006. During that time, the annual number of long-term acute care admissions after critical illness increased from 13,732 to 40,353, with annual costs increasing from $484 million to $1.325 billion. The age-standardized population incidence of long-term acute care utilization after critical illness increased from 38.1 per 100,000 in 1997 to 99.7 per 100,000 in 2006, with greater use among male individuals and black individuals in all periods. Over time, transferred patients had higher numbers of comorbidities (5.0 in 1997-2000 vs 5.8 in 2004-2006, P < .001) and were more likely to receive mechanical ventilation at the long-term acute care hospital (16.4% in 1997-2000 vs 29.8% in 2004-2006, P < .001). One-year mortality after long-term acute care hospital admission was high throughout the study period: 50.7% in 1997-2000 and 52.2% in 2004-2006.

Conclusions: Long-term acute care hospital utilization after critical illness is common and increasing. Survival among Medicare beneficiaries transferred to long-term acute care after critical illness is poor.
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http://dx.doi.org/10.1001/jama.2010.761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3094575PMC
June 2010

The use of angiogenic factors in discriminating preeclampsia: are they ready for prime time?

J Matern Fetal Neonatal Med 2010 Nov;23(11):1294-300

Department of Obstetrics and Gynecology, University of Pennsylvania Health System, Philadelphia, PA 19104, USA.

Objectives: We sought to evaluate the association between soluble fms-like tyrosine kinase 1 (sFlt1) and endoglin (ENG) and preeclampsia in an urban population, to develop a discriminatory model, and evaluate the association of these biomarkers with small for gestational age (SGA).

Methods: Cases are prospectively identified with preeclampsia. Controls are term patients without preeclampsia. Commercially available ELISAs were used to measure levels of sFlt1, ENG, and placental growth factor (PlGF). Log-transformed levels were compared and multivariable logistic regression analyses were performed to control for confounders. Receiver operating characteristic curves were developed.

Results: In cases (n=86) compared to controls (n=288), sFlt1 (p=0.24) levels were no different. However, ENG levels were higher (p<0.001), and PlGF levels were lower (p<0.001). Further, levels of sFlt1 had poor discriminatory ability between cases and controls [AUC=0.56, (0.48–0.63)]. The best model to discriminate between groups included clinical risk factors, ENG, and PlGF [AUC=0.89, (0.85–0.92)].

Conclusions: Unlike recent reports, this study suggests that sFlt1 may have limited diagnostic utility in predicting preeclampsia, especially term disease.
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http://dx.doi.org/10.3109/14767051003677988DOI Listing
November 2010

Evidence of a gene-environment interaction that predisposes to spontaneous preterm birth: a role for asymptomatic bacterial vaginosis and DNA variants in genes that control the inflammatory response.

Am J Obstet Gynecol 2010 Apr;202(4):386.e1-6

Division of Maternal-Fetal Medicine, Maternal and Child Research Program, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Objective: We determined whether an environmental exposure to bacterial vaginosis (BV) modified genetic susceptibilities for spontaneous preterm delivery within genes that regulate the inflammatory response.

Study Design: Maternal DNA samples and vaginal smears for Gram staining were collected from 743 women (68 preterm births). We used a 1536-single nucleotide polymorphism (SNP) custom chip to study associations between genotype distributions and preterm birth.

Results: For 8 SNPs in 3 genes (protein kinase C alpha, fms-like tyrosine kinase 1, and interleukin 6), the odds ratios for preterm birth ranged from 1.9-4.0 among women with susceptible genotypes who were BV positive. The odds ratios for preterm birth were 2.0-5.0 times greater among women who were BV positive than among women who were BV negative. The significance of these differences was demonstrated by logistic regression analyses for genotype/BV interaction.

Conclusion: These results demonstrate that the risk of preterm delivery that is associated with tag SNPs in genes that regulate the inflammatory response is modified by an environmental exposure such as bacterial vaginosis.
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http://dx.doi.org/10.1016/j.ajog.2010.01.042DOI Listing
April 2010

Treatment of localized periodontal disease in pregnancy does not reduce the occurrence of preterm birth: results from the Periodontal Infections and Prematurity Study (PIPS).

Am J Obstet Gynecol 2010 Feb;202(2):147.e1-8

Department of Obstetrics and Gynecology, Washington University in St. Louis, School of Medicine, Campus Box 8064, 4911 Barnes-Jewish Hospital Plaza, St. Louis, MO 63110-1094, USA.

Objective: The purpose of this study was to test whether treating periodontal disease (PD) in pregnancy will reduce the incidence of spontaneous preterm delivery (SPTD) at < or = 35 weeks of gestation.

Study Design: A multicenter, randomized clinical trial was performed. Subjects with PD were randomized to scaling and root planing (active) or tooth polishing (control). The primary outcome was the occurrence of SPTD at <35 weeks of gestation.

Results: We screened 3563 subjects for PD; the prevalence of PD was 50%. Seven hundred fifty-seven subjects were assigned randomly; 378 subjects were assigned to the active group, and 379 subjects were assigned to the placebo group. Active treatment did not reduce the risk of SPTD at <35 weeks of gestation (relative risk, 1.19; 95% confidence interval [CI], 0.62-2.28) or composite neonatal morbidity (relative risk, 1.30; 95% CI, 0.83-2.04). There was a suggestion of an increase in the risk of indicated SPTD at <35 weeks of gestation in those subjects who received active treatment (relative risk, 3.01; 95% CI, 0.95-4.24).

Conclusion: Treating periodontal disease does not reduce the incidence of SPTD.
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http://dx.doi.org/10.1016/j.ajog.2009.10.892DOI Listing
February 2010
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