Person: Horowitz, Gary Leigh
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Horowitz
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Gary Leigh
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Horowitz, Gary Leigh
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Publication Attitudes to Mesalamine Questionnaire: A Novel Tool to Predict Mesalamine Nonadherence in Patients with IBD(Springer Nature, 2014) Moss, Alan; Lillis, Yvonne; Edwards George, Jessica B.; Choudhry, Niteesh; Berg, Anders; Cheifetz, Adam; Horowitz, Gary Leigh; Leffler, DanielOBJECTIVES: Poor adherence to mesalamine is common and driven by a combination of lifestyle and behavioral factors, as well as health beliefs. We sought to develop a valid tool to identify barriers to patient adherence and predict those at risk for future nonadherence. METHODS: A 10-item survey was developed from patient-reported barriers to adherence. The survey was administered to 106 patients with ulcerative colitis who were prescribed mesalamine, and correlated with prospectively collected 12-month pharmacy refills (medication possession ratio (MPR)), urine levels of salicylates, and self-reported adherence (Morisky Medication Adherence Scale (MMAS)-8). RESULTS: From the initial 10-item survey, 8 items correlated highly with the MMAS-8 score at enrollment. Computer-generated randomization produced a derivation cohort of 60 subjects and a validation cohort of 46 subjects to assess the survey items in their ability to predict future adherence. Two items from the patient survey correlated with objective measures of long-term adherence: their belief in the importance of maintenance mesalamine even when in remission and their concerns about side effects. The additive score based on these two items correlated with 12-month MPR in both the derivation and validation cohorts (P<0.05). Scores on these two items were associated with a higher risk of being nonadherent over the subsequent 12 months (relative risk (RR) =2.2, 95% confidence interval=1.5–3.5, P=0.04). The area under the curve for the performance of this 2-item tool was greater than that of the 10-item MMAS-8 score for predicting MPR scores over 12 months (area under the curve 0.7 vs. 0.5). CONCLUSIONS: Patients’ beliefs about the need for maintenance mesalamine and their concerns about side effects influence their adherence to mesalamine over time. These concerns could easily be raised in practice to identify patients at risk of nonadherence (Clinical Trial number NCT01349504).Publication The association of circulating angiogenic factors and HbA1c with the risk of preeclampsia in women with preexisting diabetes(Informa UK Limited, 2014) Cohen, Allison L.; Wenger, Julia B.; James-Todd, Tamarra; Lamparello, Brooke M.; Halprin, Elizabeth; Serdy, Shanti; Fan, Shuling; Horowitz, Gary Leigh; Lim, Kee-Hak; Rana, Sarosh; Takoudes, Tamara C.; Wyckoff, Jennifer A.; Thadhani, Ravi; Karumanchi, Subbian; Brown, FlorenceObjective: To assess whether glycemic control, soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF) were associated with the development of preeclampsia (PE) or gestational hypertension (GHTN) in women with preexisting diabetes. Methods: Maternal circulating angiogenic factors (sFlt1 and PlGF) measured on automated platform were studied at four time points during pregnancy in women with diabetes (N = 159) and reported as multiples of the median (MOM) of sFlt1/PlGF ratio (median, 25th–75th percentile) noted in non-diabetic non-hypertensive control pregnant population (N = 139). Diagnosis of PE or GHTN was determined by review of de-identified clinical data. Results: PE developed in 12% (N = 19) and GHTN developed in 23% (N = 37) of the women with diabetes. Among diabetic women without PE or GHTN, median sFlt1/PlGF levels at 35–40 weeks was threefold higher than in non-diabetic controls [MOM 3.21(1.19–7.24), p = 0.0001]. Diabetic women who subsequently developed PE had even greater alterations in sFlt1/PlGF ratio during the third trimester [MOM for PE at 27–34 weeks 15.18 (2.37–26.86), at 35–40 weeks 8.61(1.20–18.27), p ≤ 0.01 for both windows compared to non-diabetic controls]. Women with diabetes who subsequently developed GHTN also had significant alterations in angiogenic factors during third trimester; however, these findings were less striking. Among women with diabetes, glycosylated hemoglobin (HbA1c) during the first trimester was higher in subjects who subsequently developed PE (7.7 vs 6.7%, p = 0.0001 for diabetic PE vs diabetic non-PE). Conclusions: Women with diabetes had a markedly altered anti-angiogenic state late in pregnancy that was further exacerbated in subjects who developed PE. Altered angiogenic factors may be one mechanism for the increased risk of PE in this population. Increased HbA1c in the first trimester of pregnancies in women with diabetes was strongly associated with subsequent PE.Publication Modeling risk for severe adverse outcomes using angiogenic factor measurements in women with suspected preterm preeclampsia(Blackwell Publishing Ltd, 2015) Palomaki, Glenn E; Haddow, James E; Haddow, Hamish R M; Salahuddin, Saira; Geahchan, Carl; Cerdeira, Ana Sofia; Verlohren, Stefan; Perschel, Frank H; Horowitz, Gary Leigh; Thadhani, Ravi; Karumanchi, S Ananth; Rana, SaroshIntroduction: Preeclampsia (PE) is a pregnancy-specific syndrome associated with adverse maternal and fetal outcomes. Patient-specific risks based on angiogenic factors might better categorize those who might have a severe adverse outcome. Methods: Women evaluated for suspected PE at a tertiary hospital (2009–2012) had pregnancy outcomes categorized as ‘referent’ or ‘severe’, based solely on maternal/fetal findings. Outcomes that may have been influenced by a PE diagnosis were considered ‘unclassified’. Soluble fms-like tyrosine kinase (sFlt1) and placental growth factor (PlGF) were subjected to bivariate discriminant modeling, allowing patient-specific risks to be assigned for severe outcomes. Results: Three hundred twenty-eight singleton pregnancies presented at ≤34.0 weeks' gestation. sFlt1 and PlGF levels were adjusted for gestational age. Risks above 5 : 1 (10-fold over background) occurred in 77% of severe (95% CI 66 to 87%) and 0.7% of referent (95% CI <0.1 to 3.8%) outcomes. Positive likelihood ratios for the modeling and validation datasets were 19 (95% CI 6.2–58) and 15 (95% CI 5.8–40) fold, respectively. Conclusions: This validated model assigns patient-specific risks of any severe outcome among women attending PE triage. In practice, women with high risks would receive close surveillance with the added potential for reducing unnecessary preterm deliveries among remaining women. © 2015 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.Publication Raman Spectroscopy Provides a Powerful Diagnostic Tool for Accurate Determination of Albumin Glycation(Public Library of Science, 2012) Dingari, Narahara Chari; Horowitz, Gary Leigh; Kang, Jeon Woong; Dasari, Ramachandra R.; Barman, IshanWe present the first demonstration of glycated albumin detection and quantification using Raman spectroscopy without the addition of reagents. Glycated albumin is an important marker for monitoring the long-term glycemic history of diabetics, especially as its concentrations, in contrast to glycated hemoglobin levels, are unaffected by changes in erythrocyte life times. Clinically, glycated albumin concentrations show a strong correlation with the development of serious diabetes complications including nephropathy and retinopathy. In this article, we propose and evaluate the efficacy of Raman spectroscopy for determination of this important analyte. By utilizing the pre-concentration obtained through drop-coating deposition, we show that glycation of albumin leads to subtle, but consistent, changes in vibrational features, which with the help of multivariate classification techniques can be used to discriminate glycated albumin from the unglycated variant with 100% accuracy. Moreover, we demonstrate that the calibration model developed on the glycated albumin spectral dataset shows high predictive power, even at substantially lower concentrations than those typically encountered in clinical practice. In fact, the limit of detection for glycated albumin measurements is calculated to be approximately four times lower than its minimum physiological concentration. Importantly, in relation to the existing detection methods for glycated albumin, the proposed method is also completely reagent-free, requires barely any sample preparation and has the potential for simultaneous determination of glycated hemoglobin levels as well. Given these key advantages, we believe that the proposed approach can provide a uniquely powerful tool for quantification of glycation status of proteins in biopharmaceutical development as well as for glycemic marker determination in routine clinical diagnostics in the future.Publication Pre-eclampsia, Soluble fms-like Tyrosine Kinase 1, and the Risk of Reduced Thyroid Function: Nested Case-Control and Population Based Study(BMJ Publishing Group, 2009) Levine, Richard J; Vatten, Lars Johan; Horowitz, Gary Leigh; Qian, Cong; Romundstad, Pal R; Yu, Kai F; Hollenberg, Anthony; Hellevik, Alf I; Asvold, Bjorn O; Karumanchi, SubbianObjective: To determine if pre-eclampsia is associated with reduced thyroid function during and after pregnancy. Design: Nested case-control study during pregnancy and population based follow-up study after pregnancy. Setting: Calcium for Pre-eclampsia Prevention trial of healthy pregnant nulliparous women in the United States during 1992-5, and a Norwegian population based study (Nord-Trondelag Health Study or HUNT-2) during 1995-7 with linkage to the medical birth registry of Norway. Participants: All 141 women (cases) in the Calcium for Pre-eclampsia Prevention trial with serum measurements before 21 weeks’ gestation (baseline) and after onset of pre-eclampsia (before delivery), 141 normotensive controls with serum measurements at similar gestational ages, and 7121 women in the Nord-Trondelag Health Study whose first birth had occurred in 1967 or later and in whom serum levels of thyroid stimulating hormone had been subsequently measured. Main outcome measures: Thyroid function tests and human chorionic gonadotrophin and soluble fms-like tyrosine kinase 1 concentrations in the Calcium for Pre-eclampsia Prevention cohort and odds ratios for levels of thyroid stimulating hormone above the reference range, according to pre-eclampsia status in singleton pregnancies before the Nord-Trondelag Health Study. Results: In predelivery specimens of the Calcium for Pre-eclampsia Prevention cohort after the onset of pre-eclampsia, thyroid stimulating hormone levels increased 2.42 times above baseline compared with a 1.48 times increase in controls. The ratio of the predelivery to baseline ratio of cases to that of the controls was 1.64 (95% confidence interval 1.29 to 2.08). Free triiodothyronine decreased more in the women with pre-eclampsia than in the controls (case ratio to control ratio 0.96, 95% confidence interval 0.92 to 0.99). The predelivery specimens but not baseline samples from women with pre-eclampsia were significantly more likely than those from controls to have concentrations of thyroid stimulating hormone above the reference range (adjusted odds ratio 2.2, 95% confidence interval 1.1 to 4.4). Both in women who developed pre-eclampsia and in normotensive controls the increase in thyroid stimulating hormone concentration between baseline and predelivery specimens was strongly associated with increasing quarters of predelivery soluble fms-like tyrosine kinase 1 (P for trend 0.002 and <0.001, respectively). In the Nord-Trondelag Health Study, women with a history of pre-eclampsia in their first pregnancy were more likely than other women (adjusted odds ratio 1.7, 95% confidence interval 1.1 to 2.5) to have concentrations of thyroid stimulating hormone above the reference range (>3.5 mIU/l). In particular, they were more likely to have high concentrations of thyroid stimulating hormone without thyroid peroxidase antibodies (adjusted odds ratio 2.6, 95% confidence interval 1.3 to 5.0), suggesting hypothyroid function in the absence of an autoimmune process. This association was especially strong (5.8, 1.3 to 25.5) if pre-eclampsia had occurred in both the first and the second pregnancies. Conclusion: Increased serum concentration of soluble fms-like tyrosine kinase 1 during pre-eclampsia is associated with subclinical hypothyroidism during pregnancy. Pre-eclampsia may also predispose to reduced thyroid function in later years.