Publications by authors named "Rosalind Tang"

7 Publications

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Inhaled nitric oxide improves the hepatopulmonary syndrome: a physiologic analysis.

Thorax 2021 Apr 15. Epub 2021 Apr 15.

Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

The hepatopulmonary syndrome (HPS) is defined by liver dysfunction, intrapulmonary vasodilatation and abnormal oxygenation. Hypoxaemia is progressive and liver transplant is the only effective treatment. Severe hypoxaemia is a life-threatening HPS complication, particularly after transplant. We evaluated gas-exchange and haemodynamic effects of invasive therapies in a consecutive sample of 26 pre-transplant patients. Inhaled nitric oxide significantly improved partial pressure of oxygen (12.4 mm Hg; p=0.001) without deleterious effects on cardiac output. Trendelenburg positioning resulted in a small improvement, and methylene blue did not, though individual responses were variable. Future studies should prospectively evaluate these strategies in severe post-transplant hypoxaemia.
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http://dx.doi.org/10.1136/thoraxjnl-2020-216128DOI Listing
April 2021

Adverse childhood experiences, DNA methylation age acceleration, and cortisol in UK children: a prospective population-based cohort study.

Clin Epigenetics 2020 04 7;12(1):55. Epub 2020 Apr 7.

MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.

Background: Epigenetic mechanisms may partly explain the persistent effects of adverse childhood experiences (ACEs) on health outcomes in later life. DNA methylation can predict chronological age, and advanced methylation-predicted age beyond chronological age (DNA methylation age acceleration) is associated with ACEs, adverse mental and physical health, and elevated diurnal and baseline salivary cortisol. Childhood adversity is also associated with dysregulation of the hypothalamic-pituitary-adrenal axis, which produces the neuroendocrine hormone cortisol. It remains unknown whether these associations are specific to certain types of adversity. Herein, we investigate the associations of ACEs with DNA methylation age acceleration and plasma cortisol in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort.

Methods: In this study of the children in ALSPAC, we used multiple linear regression to examine associations of cumulative exposure to ACE, as well as exposure to ten individual types of ACEs, with Horvath-estimated DNA methylation age acceleration and with baseline plasma cortisol. The ten ACEs were those included in the World Health Organization's ACE International Questionnaire. Data on ACEs were prospectively collected from age 0-14 years. DNA methylation age acceleration and plasma cortisol were measured at mean 17.1 years and 15.5 years, respectively.

Results: We included 974 UK children in the present study. Exposure to four or more ACEs compared to zero was associated with DNA methylation age acceleration in girls (β, 95% CI = 1.65, 0.25 to 3.04 years) but not in boys (β, 95% CI = - 0.11, - 1.48 to 1.26 years). Also, in girls, emotional abuse and physical abuse were each associated with DNA methylation age acceleration (β, 95% CI = 1.20, 0.15 to 2.26 years and β, 95% CI = 1.22, 0.06 to 2.38 years, respectively). No other ACEs were associated with accelerated DNA methylation age in either sex. Associations were also null between ACE and cortisol, and cortisol and DNA methylation age acceleration.

Conclusions: In this prospective population-based study of UK children, cumulative ACE exposure, emotional abuse, and physical abuse between age 0 and 14 years were each associated with Horvath-estimated DNA methylation age acceleration at age 17 years in girls but not in boys.
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http://dx.doi.org/10.1186/s13148-020-00844-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137290PMC
April 2020

Female reproductive history in relation to chronic obstructive pulmonary disease and lung function in UK biobank: a prospective population-based cohort study.

BMJ Open 2019 10 28;9(10):e030318. Epub 2019 Oct 28.

MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.

Objectives: Sex differences in respiratory physiology and predilection for developing chronic obstructive pulmonary disease (COPD) have been documented, suggesting that female sex hormones may influence pathogenesis. We investigated whether aspects of female reproductive health might play a role in risk of COPD among women.

Design: Population-based prospective cohort study.

Setting: UK Biobank recruited across 22 centres in the UK between 2006 to 2010.

Primary And Secondary Outcomes Measures: We examined a range of female reproductive health indicators in relation to risk of COPD-related hospitalisation/death (n=271 271) using Cox proportional hazards regression; and lung function (n=273 441) using linear regression.

Results: Parity >3 was associated with greater risk of COPD-related hospitalisation/death (adjusted HR 1.45; 95% CI: 1.16 to 1.82) and lower forced expiratory volume at 1 second/forced vital capacity ratio (FEV/FVC) (adjusted mean difference -0.06; 95% CI: -0.07 to 0.04). Any oral contraception use was associated with lower risk of COPD-related hospitalisation/death (adjusted HR 0.85; 95% CI: 0.74 to 0.97) and greater FEV/FVC (adjusted mean difference 0.01; 95% CI: 0.003 to 0.03). Late menarche (age >15) and early menopause (age <47) were also associated with greater risk of COPD-related hospitalisation/death (but not lung function), while endometriosis was associated with greater FEV/FVC (not COPD-related hospitalisation/death). Early menarche (age <12 years) was associated with lower FEV/FVC (but not COPD hospitalisation/death). Associations with polycystic ovary syndrome (PCOS) or ovarian cysts, any hormone replacement therapy (HRT) use, hysterectomy-alone and both hysterectomy and bilateral oophorectomy were in opposing directions for COPD-related hospitalisation/death (greater risk) and FEV/FVC (positive association).

Conclusions: Multiple female reproductive health indicators across the life course are associated with COPD-related hospitalisation/death and lung function. Further studies are necessary to understand the opposing associations of PCOS/ovarian cysts, HRT and hysterectomy with COPD and objective measures of airway obstruction.
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http://dx.doi.org/10.1136/bmjopen-2019-030318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830692PMC
October 2019

A Gap Analysis Assessing the Perceptions of Primary Care Physicians in the Management of Kidney Recipients After Transplantation.

Prog Transplant 2019 12 11;29(4):309-315. Epub 2019 Sep 11.

Division of Nephrology and the Kidney Transplant Program, University Health Network, Toronto, Ontario, Canada.

Objectives: To examine the practice patterns and perceptions of primary care physicians in the management of chronic diseases in kidney recipients, assess care provided to recipients, and identify barriers to the optimal delivery of primary care to recipients.

Methods: A self-administered questionnaire on the primary care of kidney recipients was developed and implemented. The survey investigated physician comfort and practice patterns in providing preventive and chronic care to recipients, patient self-management support, and physician perceptions on communication with transplant centers and barriers to ideal care.

Results: A total of 210 physicians completed the survey (response rate of 22%). Among the respondents, 73% indicated they were currently providing care to kidney recipients. The majority of physicians specified that they rarely (57%) or never (20%) communicate with transplant centers. Most physicians felt comfortable providing care to recipients for non-transplant-related issues (92.5%), vaccinations (85%), and periodic health examinations (94%). The majority (75.3%) of physicians felt uncomfortable managing the immunosuppressive medications of recipients. Physicians' most commonly stated barriers to delivering optimal care to recipients were insufficient guidelines provided by the transplant center (68.9%) and lack of knowledge in managing recipients (58.8%). Suggested resources by physicians to improve their comfort level in managing recipients included guidelines and continuing medical educational activities related to transplantation.

Conclusions: Our results suggest that there are barriers to delivering optimal primary care to kidney recipients. The approach to providing resources needed to bridge the knowledge gap for physicians in the management of recipients requires further exploration.
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http://dx.doi.org/10.1177/1526924819873911DOI Listing
December 2019

Clotting factor changes during the first cycle of oral contraceptive use.

Contraception 2016 Jan 9;93(1):70-6. Epub 2015 Oct 9.

Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Objectives: The risk of venous thromboembolism (VTE) is highest during the initial months of oral contraceptive (OC) use. We sought to evaluate the extent of hemostatic variable changes during the initial OC cycle and if such changes are related to systemic ethinyl estradiol (EE2) exposure.

Study Design: Participants provided multiple blood samples during a 21-day OC cycle (30mcg EE2; 150mcg levonorgestrel) and after a single dose following a washout period. Analytes included D-dimer, factor VIII activity, protein C total antigen and the hepatic proteins corticosteroid-binding globulin (CBG) and sex-hormone-binding globulin (SHBG). EE2 pharmacokinetic analyses related to the 24h after the first OC tablet (OC1) and at steady state (OC21).

Results: Seventeen women completed the study. D-dimer more than doubled by OC6 (p=.013) and remained elevated at OC21 (p=.012). D-dimer levels within women varied widely from day to day. Factor VIII increased 27% by OC2 (p<.001) but declined to a 9% increase by OC21. Protein C increased only 6%. EE2 steady-state area-under-the-curve ranged from 488 to 1103pg∙h/mL; higher levels were not correlated with greater increases in clotting variables. CBG and SHBG increased significantly but were not significantly correlated with levels of EE2 or with the hemostatic variables.

Conclusions: D-dimer increases during the first OC cycle were at least as great as increases seen with longer OC use. These results provide support for the increased VTE risk during initial OC use. The extreme variability in D-dimer levels may be an important component of this risk.

Implications: This study showed that increases in D-dimer are clearly evident in the first cycle of OC use and may be larger than are seen after a longer duration of use and thus provide biological support for the increased VTE risk during initial OC use found in epidemiological studies.
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http://dx.doi.org/10.1016/j.contraception.2015.09.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004596PMC
January 2016

Risk Factors for Venous Thromboembolism Among Reproductive Age Women.

J Womens Health (Larchmt) 2016 Jan 28;25(1):63-70. Epub 2015 Aug 28.

3 Department of Medicine, Columbia University Medical Center , New York, New York.

Background: Venous thromboembolism (VTE) is rare among young women and is often presumed to occur in the setting of a genetic predisposition or during the use of estrogen-containing combined hormonal contraceptive or to have an unknown cause. This study aims to describe the distribution of VTE risk factors among women with a confirmed VTE.

Methods: We identified all women aged 15-46 years with a VTE diagnosis at Columbia University Medical Center from 2005 to 2012 using medical center databases. We then reviewed all electronic medical records to validate the diagnoses and identify risk factors associated with each confirmed case.

Results: We identified 315 cases and confirmed 186 (59%). The proportion of unconfirmed cases increased over time. Forty percent of confirmed cases were associated with hormonal contraceptives or pregnancy. Ninety-five percent of confirmed cases had identifiable major risk factors including a personal history, family history, malignancy or other predisposing illness, recent long-haul travel, trauma, hospitalization, and obesity; many had multiple simultaneous risk factors. None of the confirmed cases was associated with a previously known genetic predisposition, but in 10 confirmed cases a genetic predisposition was identified during evaluation. In only 10 of the 186 confirmed cases could we not identify any acquired risk factor, and only 2 of those 10 women had a genetic predisposition.

Conclusions: Many reproductive age women experiencing a VTE have risk factors unique to this group, and most have multiple risk factors, confirming that this is a multifactorial disease. The large proportion of unconfirmed cases suggests the need for great caution in using administrative databases for research due to poor diagnostic specificity and due to lack of information about additional risk factors.
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http://dx.doi.org/10.1089/jwh.2015.5259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453493PMC
January 2016

Estimating systemic exposure to ethinyl estradiol from an oral contraceptive.

Am J Obstet Gynecol 2015 May 12;212(5):614.e1-7. Epub 2014 Dec 12.

Pathology and Cell Biology, Columbia University Medical Center, New York, NY.

Objective: This study was conducted to compare single-dose pharmacokinetics of ethinyl estradiol in an oral contraceptive with steady-state values and to assess whether any simpler measures could provide an adequate proxy of the "gold standard" 24-hour steady-state area under the curve (AUC) value. Identification of a simple, less expensive measure of systemic ethinyl estradiol exposure would be useful for larger studies that are designed to assess the relationship between an individual's ethinyl estradiol exposure and side-effects.

Study Design: We collected 13 samples over 24 hours for pharmacokinetic analysis on days 1 and 21 of the first cycle of a monophasic oral contraceptive that contained 30 μg ethinyl estradiol and 150 μg levonorgestrel in 17 nonobese healthy white women. We also conducted an abbreviated single-dose 9-sample pharmacokinetic analysis after a month washout. Ethinyl estradiol was measured by liquid chromatography-tandem mass spectrometry. We compared results of a full 13-sample steady-state pharmacokinetic analysis with results that had been calculated with the use of fewer samples (9 or 5) and after the single doses. We calculated Pearson correlation coefficients to evaluate the relationships between these estimates of systemic ethinyl estradiol exposure.

Results: The AUC, maximum, and 24-hour values were similar after the 2 single oral contraceptive doses (AUC; r=0.92). The steady-state 13-sample 24-hour AUC value was correlated highly with the average 9-sample AUC value after the 2 single doses (r=0.81; P=.0002). This correlation remained the same if the number of single-dose samples was reduced to 4, taken at time 1, 2.5, 4, and 24 hours. The 24-hour value at steady-state was correlated highly with the 24-hour steady-state AUC value (r=0.92; P<.0001). The average of the 24-hour values after the 2 single doses was also correlated quite highly with the steady-state AUC value (r=0.72; P=.0026).

Conclusion: Limited blood sampling, including results from 2 single doses, gave highly correlated estimates of an oral contraceptive user's steady-state ethinyl estradiol exposure.
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http://dx.doi.org/10.1016/j.ajog.2014.12.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417052PMC
May 2015
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