Author
Gideon Koren
Other affiliations: McGill University Health Centre, University of Western Ontario, Sunnybrook Health Sciences Centre ...read more
Bio: Gideon Koren is an academic researcher from Ariel University. The author has contributed to research in topics: Pregnancy & Population. The author has an hindex of 129, co-authored 1994 publications receiving 81718 citations. Previous affiliations of Gideon Koren include McGill University Health Centre & University of Western Ontario.
Topics: Pregnancy, Population, Motherisk, Nausea, Gestational age
Papers published on a yearly basis
Papers
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TL;DR: Identical maternal ethanol exposure levels produced differing levels of fetal exposure in a dizygotic human twin pair and a series of guinea pig littermates as evidenced through FAEE meconium analysis, indicating that the placenta may have a previously unappreciated role in mediating ethanol-induced fetal injury.
Abstract: Mediators of susceptibility to alcohol-related toxicity in the prenatal environment are relatively unknown. The placenta has been proposed as a potential source of variability in the fetal environment, primarily through its significant metabolic capabilities. Meconium is a toxicological matrix unique to the developing fetus that offers an opportunity to quantify fetal exposure to alcohol through the analysis of fatty acid ethyl esters (FAEE) [nonoxidative ethanol metabolites]. To explore the role of the placenta as a potential source of variability in mediating fetal alcohol exposure via meconium analysis of FAEE, by combining a clinical case report involving human dizygotic twins and a series of guinea pig littermates. Meconium was collected from a pair of dizygotic twins with clinical suspicion of prenatal alcohol exposure and analyzed for FAEE to confirm prenatal alcohol exposure. Meconium was also collected from a series of guinea pig pups prenatally exposed to alcohol at a daily dose of 4 g/kg/day administered to the pregnant dam. FAEE levels were analyzed by gas chromatography with flame ionization detection following liquid-liquid extraction from meconium. The dizygotic twin pair yielded positive meconium FAEE results (>2.00 nmoL/g) in the female twin (2.21 nmoL/g) and no detectable FAEE in the male twin. A total of 15 meconium samples were collected from 15 pups of five pregnant guinea pig litters. With the exception of one pair of littermates, meconium FAEE concentrations differed substantially within each litter (FAEE expressed in units of nmoL/g): litter 1 (0.996, 4.43, 1.36); litter 2 (5.17, 4.15, 0.00); litter 3 (5.16, 5.27); litter 4 (18.57, 8.26, 7.46); litter 5 (0.00, 4.32, 0.00, 1.27). Identical maternal ethanol exposure levels produced differing levels of fetal exposure in a dizygotic human twin pair and a series of guinea pig littermates as evidenced through FAEE meconium analysis. These data indicate that the placenta may have a previously unappreciated role in mediating ethanol-induced fetal injury.
26 citations
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TL;DR: A review of the advantages and shortcomings of different drug-induced and genetically mediated LQTS animal models - focusing on mouse and rabbit models since these represent the most commonly used small animal models for LQ TS that can be subjected to genetic manipulation.
Abstract: Long QT syndrome (LQTS) is a rare inherited channelopathy caused mainly by different mutations in genes encoding for cardiac K(+) or Na(+) channels, but can also be caused by commonly used ion-channel-blocking and QT-prolonging drugs, thus affecting a much larger population. To develop novel diagnostic and therapeutic strategies to improve the clinical management of these patients, a thorough understanding of the pathophysiological mechanisms of arrhythmogenesis and potential pharmacological targets is needed. Drug-induced and genetic animal models of various species have been generated and have been instrumental for identifying pro-arrhythmic triggers and important characteristics of the arrhythmogenic substrate in LQTS. However, due to species differences in features of cardiac electrical function, these different models do not entirely recapitulate all aspects of the human disease. In this review, we summarize advantages and shortcomings of different drug-induced and genetically mediated LQTS animal models - focusing on mouse and rabbit models since these represent the most commonly used small animal models for LQTS that can be subjected to genetic manipulation. In particular, we highlight the different aspects of arrhythmogenic mechanisms, pro-arrhythmic triggering factors, anti-arrhythmic agents, and electro-mechanical dysfunction investigated in transgenic LQTS rabbit models and their translational application for the clinical management of LQTS patients in detail. Transgenic LQTS rabbits have been instrumental to increase our understanding of the role of spatial and temporal dispersion of repolarization to provide an arrhythmogenic substrate, genotype-differences in the mechanisms for early afterdepolarization formation and arrhythmia maintenance, mechanisms of hormonal modification of arrhythmogenesis and regional heterogeneities in electro-mechanical dysfunction in LQTS.
25 citations
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TL;DR: The automated data-driven approach allowed us to define the frequency bands in PSD analysis of beat-to-beat time series from different mammals and demonstrated a scaling law between the GMM-identified cutoff frequencies and the typical heart rate (HRm) that can be used to approximate the PSD bands in other mammals.
Abstract: Background: Power spectral density (PSD) analysis of the heartbeat intervals in the three main frequency bands (very low frequency (VLF), low frequency (LF) and high frequency (HF)) provides a quantitative noninvasive tool for assessing the function of the cardiovascular control system In humans, these frequency bands were standardized following years of empirical evidence However, no quantitative approach has justified the frequency cutoffs of these bands and how they might be adapted to other mammals Defining mammal-specific frequency bands is necessary if the PSD analysis of the HR is to be used as a proxy for measuring the autonomic nervous system activity in animal models Methods: We first describe the distribution of prominent frequency peaks found in the normalized PSD of mammalian data using a Gaussian mixture model while assuming three components corresponding to the traditional VLF, LF and HF bands We trained the algorithm on a database of human electrocardiogram recordings (n=18) and validated it on databases of dogs (n=17) and mice (n = 7) Finally, we tested it to predict the bands for rabbits (n=4) for the first time Results: Double-logarithmic analysis demonstrates a scaling law between the GMM-identified cutoff frequencies and the typical heart rate (HRm): f_(VLF-LF)=00037∙〖HR〗_m^058,f_(LF-HF)=00017∙〖HR〗_m^101 and f_(〖HF〗_up )=00128 ∙〖HR〗_m^086 We found that the band cutoff frequencies and Gaussian mean scale with a power law of 1/4 or 1/8 of the typical body mass (BMm), thus revealing allometric power laws Conclusions: Our automated data-driven approach allowed us to define the frequency bands in PSD analysis of beat-to-beat time series from different mammals The scaling law between the band frequency cutoffs and the HRm can be used to approximate the PSD bands in other mammals
25 citations
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TL;DR: This initial report, which should be substantiated and expanded, provides information that can help counsel parents about breastfeeding and celecoxib.
Abstract: Many women of reproductive age take the nonsteroidal antiinflammatory drug celecoxib. No data exist, however, regarding its transfer into human breast milk and safety for breastfed infants. We had the opportunity to obtain such data when a woman who was breastfeeding her infant daughter underwent emergency surgery to remove a gangrenous appendix. She received four doses of oral celecoxib 100 mg and did not breastfeed her daughter for 48 hours after taking the last dose. We analyzed samples of her breast milk and found a concentration of 133 ng/ml at approximately 5 hours after a 100-mg dose and an elimination half-life of 4.0-6.5 hours. This initial report, which should be substantiated and expanded, provides information that can help counsel parents about breastfeeding and celecoxib.
25 citations
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TL;DR: The present review focuses on drug classes for which the risk:benefit ratio during pregnancy has been discussed recently based on human data.
Abstract: Most drugs are not labelled for use in pregnancy. Consequently, large numbers of women expose their fetus to potential risks, either because they do not know that they are pregnant or because they require treatment for gestational pathologies. The present review focuses on drug classes for which the risk:benefit ratio during pregnancy has been discussed recently based on human data. Selective serotonin reuptake inhibitors have gained wide acceptance in the treatment of depression and data on their risk for neonatal adaptation after late exposure are reviewed. Angiotensin converting enzyme inhibitors and angiotensin II receptors antagonists interact with the renin-angiotensin system, although with different mechanisms, and might cause severe fetal tubular dysgenesis. Non-steroidal anti-inflammatory and antiviral drugs and recreational drugs are also presented.
25 citations
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TL;DR: In this review the usual methods applied in systematic reviews and meta-analyses are outlined, and the most common procedures for combining studies with binary outcomes are described, illustrating how they can be done using Stata commands.
31,656 citations
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TL;DR: In those older than age 50, systolic blood pressure of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP, and hypertension will be controlled only if patients are motivated to stay on their treatment plan.
Abstract: The National High Blood Pressure Education Program presents the complete Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Like its predecessors, the purpose is to provide an evidence-based approach to the prevention and management of hypertension. The key messages of this report are these: in those older than age 50, systolic blood pressure (BP) of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP; beginning at 115/75 mm Hg, CVD risk doubles for each increment of 20/10 mm Hg; those who are normotensive at 55 years of age will have a 90% lifetime risk of developing hypertension; prehypertensive individuals (systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg) require health-promoting lifestyle modifications to prevent the progressive rise in blood pressure and CVD; for uncomplicated hypertension, thiazide diuretic should be used in drug treatment for most, either alone or combined with drugs from other classes; this report delineates specific high-risk conditions that are compelling indications for the use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); two or more antihypertensive medications will be required to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg) for patients with diabetes and chronic kidney disease; for patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using two agents, one of which usually will be a thiazide diuretic, should be considered; regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan. Positive experiences, trust in the clinician, and empathy improve patient motivation and satisfaction. This report serves as a guide, and the committee continues to recognize that the responsible physician's judgment remains paramount.
14,975 citations
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TL;DR: In this article, a randomized controlled trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly people was presented. But the authors did not discuss the effect of the combination therapy in patients living with systolic hypertension.
Abstract: ABCD
: Appropriate Blood pressure Control in Diabetes
ABI
: ankle–brachial index
ABPM
: ambulatory blood pressure monitoring
ACCESS
: Acute Candesartan Cilexetil Therapy in Stroke Survival
ACCOMPLISH
: Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension
ACCORD
: Action to Control Cardiovascular Risk in Diabetes
ACE
: angiotensin-converting enzyme
ACTIVE I
: Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events
ADVANCE
: Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation
AHEAD
: Action for HEAlth in Diabetes
ALLHAT
: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack
ALTITUDE
: ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints
ANTIPAF
: ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation
APOLLO
: A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People
ARB
: angiotensin receptor blocker
ARIC
: Atherosclerosis Risk In Communities
ARR
: aldosterone renin ratio
ASCOT
: Anglo-Scandinavian Cardiac Outcomes Trial
ASCOT-LLA
: Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm
ASTRAL
: Angioplasty and STenting for Renal Artery Lesions
A-V
: atrioventricular
BB
: beta-blocker
BMI
: body mass index
BP
: blood pressure
BSA
: body surface area
CA
: calcium antagonist
CABG
: coronary artery bypass graft
CAPPP
: CAPtopril Prevention Project
CAPRAF
: CAndesartan in the Prevention of Relapsing Atrial Fibrillation
CHD
: coronary heart disease
CHHIPS
: Controlling Hypertension and Hypertension Immediately Post-Stroke
CKD
: chronic kidney disease
CKD-EPI
: Chronic Kidney Disease—EPIdemiology collaboration
CONVINCE
: Controlled ONset Verapamil INvestigation of CV Endpoints
CT
: computed tomography
CV
: cardiovascular
CVD
: cardiovascular disease
D
: diuretic
DASH
: Dietary Approaches to Stop Hypertension
DBP
: diastolic blood pressure
DCCT
: Diabetes Control and Complications Study
DIRECT
: DIabetic REtinopathy Candesartan Trials
DM
: diabetes mellitus
DPP-4
: dipeptidyl peptidase 4
EAS
: European Atherosclerosis Society
EASD
: European Association for the Study of Diabetes
ECG
: electrocardiogram
EF
: ejection fraction
eGFR
: estimated glomerular filtration rate
ELSA
: European Lacidipine Study on Atherosclerosis
ESC
: European Society of Cardiology
ESH
: European Society of Hypertension
ESRD
: end-stage renal disease
EXPLOR
: Amlodipine–Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine–Atenolol Combination
FDA
: U.S. Food and Drug Administration
FEVER
: Felodipine EVent Reduction study
GISSI-AF
: Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation
HbA1c
: glycated haemoglobin
HBPM
: home blood pressure monitoring
HOPE
: Heart Outcomes Prevention Evaluation
HOT
: Hypertension Optimal Treatment
HRT
: hormone replacement therapy
HT
: hypertension
HYVET
: HYpertension in the Very Elderly Trial
IMT
: intima-media thickness
I-PRESERVE
: Irbesartan in Heart Failure with Preserved Systolic Function
INTERHEART
: Effect of Potentially Modifiable Risk Factors associated with Myocardial Infarction in 52 Countries
INVEST
: INternational VErapamil SR/T Trandolapril
ISH
: Isolated systolic hypertension
JNC
: Joint National Committee
JUPITER
: Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin
LAVi
: left atrial volume index
LIFE
: Losartan Intervention For Endpoint Reduction in Hypertensives
LV
: left ventricle/left ventricular
LVH
: left ventricular hypertrophy
LVM
: left ventricular mass
MDRD
: Modification of Diet in Renal Disease
MRFIT
: Multiple Risk Factor Intervention Trial
MRI
: magnetic resonance imaging
NORDIL
: The Nordic Diltiazem Intervention study
OC
: oral contraceptive
OD
: organ damage
ONTARGET
: ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial
PAD
: peripheral artery disease
PATHS
: Prevention And Treatment of Hypertension Study
PCI
: percutaneous coronary intervention
PPAR
: peroxisome proliferator-activated receptor
PREVEND
: Prevention of REnal and Vascular ENdstage Disease
PROFESS
: Prevention Regimen for Effectively Avoiding Secondary Strokes
PROGRESS
: Perindopril Protection Against Recurrent Stroke Study
PWV
: pulse wave velocity
QALY
: Quality adjusted life years
RAA
: renin-angiotensin-aldosterone
RAS
: renin-angiotensin system
RCT
: randomized controlled trials
RF
: risk factor
ROADMAP
: Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention
SBP
: systolic blood pressure
SCAST
: Angiotensin-Receptor Blocker Candesartan for Treatment of Acute STroke
SCOPE
: Study on COgnition and Prognosis in the Elderly
SCORE
: Systematic COronary Risk Evaluation
SHEP
: Systolic Hypertension in the Elderly Program
STOP
: Swedish Trials in Old Patients with Hypertension
STOP-2
: The second Swedish Trial in Old Patients with Hypertension
SYSTCHINA
: SYSTolic Hypertension in the Elderly: Chinese trial
SYSTEUR
: SYSTolic Hypertension in Europe
TIA
: transient ischaemic attack
TOHP
: Trials Of Hypertension Prevention
TRANSCEND
: Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease
UKPDS
: United Kingdom Prospective Diabetes Study
VADT
: Veterans' Affairs Diabetes Trial
VALUE
: Valsartan Antihypertensive Long-term Use Evaluation
WHO
: World Health Organization
### 1.1 Principles
The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology …
14,173 citations
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TL;DR: 2007 Guidelines for the Management of Arterial Hypertension : The Task Force for the management of Arterspertension of the European Society ofhypertension (ESH) and of theEuropean Society of Cardiology (ESC).
Abstract: 2007 Guidelines for the Management of Arterial Hypertension : The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).
9,932 citations
01 Jan 2014
TL;DR: These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care.
Abstract: XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.
9,618 citations