Showing papers by "Gideon Koren published in 2014"
TL;DR: The current evidence assessed in the clinical practice guideline prepared by the Canadian Hypertensive Disorders of Pregnancy Working Group and published by Pregnancy Hypertension to provide a reasonable approach to the diagnosis, evaluation, and treatment of the hypertensive disorders of pregnancy is presented.
Abstract: Objective: This executive summary presents in brief the current evidence assessed in the clinical practice guideline prepared by the Canadian Hypertensive Disorders of Pregnancy Working Group and published by Pregnancy Hypertension (http://www.pregnancyhypertension.org/article/S22107789(14)00004-X/fulltext) to provide a reasonable approach to the diagnosis, evaluation, and treatment of the hypertensive disorders of pregnancy.
367 citations
TL;DR: Revealing differences in how MSCs are affected by age could help identify an optimal cell source for musculoskeletal therapies targeting older patients, and indicates the importance of age as a factor when designing cell-based therapies for older patients.
Abstract: Mesenchymal stem/stromal cells (MSCs) are promising cell sources for regenerative therapies due to their multipotency and ready availability, but their application can be complicated by patient-specific factors like age or illness. MSCs have been investigated for the treatment of many musculoskeletal disorders, including osteoarthritis and osteoporosis. Due to the prevalence of these diseases in older populations, researchers have studied how aging affects MSC properties and have found that proliferation and differentiation potential are impaired. However, these effects have never been compared among MSCs isolated from multiple tissue sources in the same, healthy donor. Revealing differences in how MSCs are affected by age could help identify an optimal cell source for musculoskeletal therapies targeting older patients. MSCs were isolated from young and old rabbit bone marrow, muscle, and adipose tissue. Cell yield and viability were quantified after isolation procedures, and expansion properties were assessed using assays for proliferation, senescence, and colony formation. Multipotency was also examined using lineage-specific stains and spectrophotometry of metabolites. Results were compared between age groups and among MSC sources. Results showed that MSCs are differentially influenced by aging, with bone marrow-derived stem cells having impaired proliferation, senescence, and chondrogenic response, whereas muscle-derived stem cells and adipose-derived stem cells exhibited no negative effects. While age reduced overall cell yield and adipogenic potential of all MSC populations, osteogenesis and clonogenicity remained unchanged. These findings indicate the importance of age as a factor when designing cell-based therapies for older patients.
254 citations
TL;DR: The aim of this study was to evaluate the risk of spontaneous abortion, major birth defects, elective termination of pregnancy, shortened gestational age at delivery, and reduced birth weight in women exposed to MTX.
Abstract: Objective
High-dose methotrexate (MTX) exposure during pregnancy is associated with embryopathy. The teratogenic potential of MTX at dosages typically used in the treatment of rheumatic diseases remains uncertain. The aim of this study was to evaluate the risk of spontaneous abortion, major birth defects, elective termination of pregnancy, shortened gestational age at delivery, and reduced birth weight in women exposed to MTX.
Methods
Pregnancy outcome in women taking MTX (≤30 mg/week) either after conception or within the 12 weeks before conception was evaluated in a prospective observational multicenter cohort study. Pregnancy outcomes in the MTX group were compared to outcomes in a group of disease-matched women and a group of women without autoimmune diseases (neither group was exposed to MTX).
Results
The study sample included 324 MTX-exposed pregnancies (188 exposed post-conception, 136 exposed pre-conception), 459 disease-matched comparison women, and 1,107 comparison women without autoimmune diseases. In the post-conception cohort, the cumulative incidence of spontaneous abortion was 42.5% (95% confidence interval [95% CI] 29.2–58.7), which was significantly higher than the incidence of spontaneous abortion in either comparison group. The risk of major birth defects (7 of 106 [6.6%]) was elevated compared to both the cohort of women without autoimmune diseases (29 of 1,001 [2.9%]) (adjusted odds ratio [OR] 3.1 [95% CI 1.03–9.5]) and the disease-matched cohort (14 of 393 [3.6%]) (adjusted OR 1.8 [95% CI 0.6–5.7]). None of the malformations were clearly consistent with MTX embryopathy. Neither the cumulative incidence of spontaneous abortion (14.4% [95% CI 8.0–25.3]) nor the risk of major birth defects (4 of 114 [3.5%]) was increased in the pre-conception cohort. Elective termination rates were increased in both of the MTX-exposed cohorts. There were no other significant differences among groups in other study end points.
Conclusion
Post-conception administration of MTX at dosages typically used in the treatment of rheumatic diseases was associated with an increased risk of major birth defects and spontaneous abortion. Such evidence was not found among women in our pre-conception cohort.
154 citations
TL;DR: The risk of persistent pulmonary hypertension of the newborn seems to be increased for infants exposed to SSRIs in late pregnancy, independent of the potential moderator variables examined.
Abstract: Objective To examine the risk for persistent pulmonary hypertension of the newborn associated with antenatal exposure to antidepressants. Design Systematic review and meta-analysis. Data sources Embase, Medline, PsycINFO, and CINAHL from inception to 30 December 2012. Eligibility English language studies reporting persistent pulmonary hypertension of the newborn associated with exposure to antidepressants. Two independent reviewers extracted data and assessed the quality of each article. Results Of the 3077 abstracts reviewed, 738 papers were retrieved and seven included. All seven studies were above our quality threshold. Quantitative analysis was only possible for selective serotonin reuptake inhibitors (SSRIs). Although exposure to SSRIs in early pregnancy was not associated with persistent pulmonary hypertension of the newborn (odds ratio 1.23, 95% confidence interval 0.58 to 2.60; P=0.58), exposure in late pregnancy was (2.50, 1.32 to 4.73; P=0.005). Effects were not significant for any of the moderator variables examined, including study design, congenital malformations, and meconium aspiration. It was not possible to assess for the effect of caesarean section, body mass index, or preterm delivery. The absolute risk difference for development of persistent pulmonary hypertension of the newborn after exposure to SSRIs in late pregnancy was 2.9 to 3.5 per 1000 infants; therefore an estimated 286 to 351 women would need to be treated with an SSRI in late pregnancy to result in an average of one additional case of persistent pulmonary hypertension of the newborn. Conclusions The risk of persistent pulmonary hypertension of the newborn seems to be increased for infants exposed to SSRIs in late pregnancy, independent of the potential moderator variables examined. A significant relation for exposure to SSRIs in early pregnancy was not evident. Although the statistical association was significant, clinically the absolute risk of persistent pulmonary hypertension of the newborn remained low even in the context of late exposure to SSRIs.
152 citations
TL;DR: If maternal self-reports are the sole information source upon which health care professionals rely, a number of infants who were prenatally exposed to alcohol are not being recognized as such.
Abstract: Maternal self-reports, used for the detection of prenatal alcohol exposure (PAE), may lack validity, necessitating the use of an objective biomarker. The detection of fatty acid ethyl esters (products of non-oxidative ethanol metabolism) in meconium has been established as a novel biomarker of PAE. The purpose of the current study was to compare the prevalence of PAE as reported via maternal self-reports with the results of meconium testing, and to quantify the disparity between these two methods. A systematic literature search for studies reporting on the prevalence of PAE, using maternal self-reports in combination with meconium testing, was conducted using multiple electronic bibliographic databases. Pooled prevalence estimates and 95% confidence intervals (CI) were calculated based on eight studies, using the Mantel-Haenszel method, assuming a random effects model. A random effects meta-regression was performed to test for a difference. The pooled prevalence of PAE as measured by meconium testing was 4.26 (95% CI: 1.34-13.57) times the pooled prevalence of PAE as measured by maternal self-reports. Large variations across the studies in regard to the difference between estimates obtained from maternal self-reports and those obtained from meconium testing were observed. If maternal self-reports are the sole information source upon which health care professionals rely, a number of infants who were prenatally exposed to alcohol are not being recognized as such. However, further research is needed in order to validate existing biomarkers, as well as discover new biomarkers, for the detection of PAE.
136 citations
TL;DR: Given the known risks of teratogenicity in animals and the present data, women of childbearing potential should use effective contraception during fingolimod therapy and for 2 months after discontinuation.
Abstract: Objective: To report outcomes of pregnancies that occurred during the fingolimod clinical development program. Methods: Pregnancy outcomes from phase II, phase III, and phase IV clinical studies (with optional extensions) were reported by clinical trial investigators. Fingolimod exposure in utero was defined as fingolimod treatment at the time of conception or in the 6 weeks before conception. Results: As of October 31, 2011, 89 pregnancies were reported in completed or ongoing clinical studies, with 74 in fingolimod treatment arms. Of 66 pregnancies with in utero exposure to fingolimod, there were 28 live births, 9 spontaneous abortions, 24 elective abortions, 4 ongoing pregnancies, and 1 pregnancy with an unknown outcome (patient lost to follow-up). Two infants were born with malformations: 1 with congenital unilateral posteromedial bowing of the tibia and 1 with acrania. Elective abortions were performed for 1 case each of tetralogy of Fallot, spontaneous intrauterine death, and failure of fetal development. There were 5 cases (7.6%; 95% confidence interval 3%–17%) of abnormal fetal development in the 66 pregnancies that had in utero exposure to fingolimod. In all 5 cases, fetal exposure to the drug took place in the first trimester of pregnancy. Conclusions: The number of patients becoming pregnant during fingolimod therapy remains small and does not permit firm conclusions to be drawn about fetal safety of fingolimod in humans. Given the known risks of teratogenicity in animals and the present data, women of childbearing potential should use effective contraception during fingolimod therapy and for 2 months after discontinuation.
129 citations
Journal Article•
TL;DR: A growing body of literature investigating the effects of not treating depression on mother and developing fetus suggests that untreated depression is associated with adverse fetal outcomes and a higher risk of maternal morbidity, including suicide ideation and attempts, and postpartum depression.
Abstract: QUESTION: One of my patients who was taking an antidepressant for major depression is now pregnant and does not wish to take it any more. I believe she needs to continue her medication. She, however, is adamant about stopping it because she believes it would put her baby at risk. Is there evidence that not treating depression during pregnancy puts babies at risk? ANSWER: A growing body of literature investigating the effects of not treating depression on mother and developing fetus suggests that untreated depression is associated with adverse fetal outcomes and a higher risk of maternal morbidity, including suicide ideation and attempts, and postpartum depression.
107 citations
TL;DR: In this article, the authors examined the evidence guiding management of multiple sclerosis in reproductive-aged women and conducted an electronic literature search using PubMed, ClinicalTrials.gov, and other available resources.
99 citations
01 Jan 2014
TL;DR: The reviewed data support the conclusion that in the majority of cases, women with MS can safely choose to become pregnant, give birth, and breastfeed children.
Abstract: OBJECTIVE: To examine the evidence guiding management of multiple sclerosis (MS) in reproductive-aged women. DATA SOURCES: We conducted an electronic literature search using PubMed, ClinicalTrials.gov, and other available resources. The following keywords were used: “multiple sclerosis” and “pregnancy.” We manually searched the reference lists of identified studies. METHODS OF STUDY SELECTION: Two reviewers categorized all studies identified in the search by management topic, including effect of pregnancy on MS course, fetal risks associated with disease-modifying treatments during pregnancy, and management of patients off disease-modifying treatment. We categorized studies by strength of evidence and included prior meta-analyses and systematic studies. These studies were then summarized and discussed by an expert multidisciplinary team.
85 citations
TL;DR: Overall, HCC was associated with mental health-related variables mainly reflecting substance use or experiencing a disability, and preliminary analyses suggest a significant curvilinear relationship between HCC and perceived stress.
Abstract: A pooled database from diverse community samples was used to examine the associations of hair cortisol concentration (HCC) with self-reported stress and stress-linked mental health measures, including depression, anxiety, alcohol and drug use, disability and experiences with aggression. As part of innovative research using a mobile laboratory to study community mental health, data were pooled from five sub-studies: a random sample of the general population (n = 70), people who had received treatment for a mental health and/or substance use problem (n = 78), family members of people treated for mental health and/or substance use problems (n = 49), community volunteers who sometimes felt sad or blue or thought they drank too much (n = 83) and young adults in intimate partner relationships (n = 44). All participants completed a computerized questionnaire including standard measures of perceived stress, chronic stress, depression, anxiety, hazardous drinking, tobacco use, prescription drug use, illicit drug use, disability and intimate partner aggression. HCC was significantly associated with use of antidepressants, hazardous drinking, smoking and disability after adjusting for sub-study and potential confounders (sex, body-mass index, use of glucocorticoids and hair dyed). In addition, preliminary analyses suggest a significant curvilinear relationship between HCC and perceived stress; specifically, HCC increased with higher perceived stress but decreased at the highest level of stress. Overall, HCC was associated with mental health-related variables mainly reflecting substance use or experiencing a disability. The relationship between HCC and self-reported stress is unclear and needs further research.
81 citations
TL;DR: Observed benznidazole plasma concentrations in children were markedly lower than those previously reported in adults (treated with comparable mg/kg doses), possibly due to a higher CL/F in smaller children, which was associated to a high therapeutic response in this cohort.
Abstract: Introduction
Chagas disease, caused by the parasite Trypanosoma cruzi, can lead to long term cardiac morbidity. Treatment of children with benznidazole is effective, but no pediatric pharmacokinetics data are available and clinical pharmacology information on the drug is scarce.
Patients and Methods
Prospective population pharmacokinetic (PK) cohort study in children 2–12 years old with Chagas disease treated with oral benznidazole 5–8 mg/kg/day BID for 60 days. (clinicaltrials.gov #NCT00699387).
Results
Forty children were enrolled in the study. Mean age was 7.3 years. A total of 117 samples were obtained from 38 patients for PK analysis. A one compartment model best fit the data. Weight-corrected clearance rate (CL/F) showed a good correlation with age, with younger patients having a significantly higher CL/F than older children and adults. Simulated median steady-state benznidazole concentrations, based on model parameters, were lower for children in our study than for adults and lowest for children under 7 years of age. Treatment was efficacious in the 37 patients who completed the treatment course, and well tolerated, with few, and mild, adverse drug reactions (ADRs).
Discussion
Observed benznidazole plasma concentrations in children were markedly lower than those previously reported in adults (treated with comparable mg/kg doses), possibly due to a higher CL/F in smaller children. These lower blood concentrations were nevertheless associated to a high therapeutic response in our cohort. Unlike adults, children have few adverse reactions to the drug, suggesting that there may be a direct correlation between drug concentrations and incidence of ADRs. Our results suggest that studies with lower doses in adults may be warranted.
Trial Registration
ClinicalTrails.gov NCT00699387
TL;DR: The role of sex hormones in modifying the dynamic spatiotemporal (regional and transmural) heterogeneities in action potential duration and the susceptibility to (sympathetic) triggered activity at the tissue, organ, and whole animal levels is examined.
TL;DR: A high precision study of the polarimetry properties of the cuprates in the THz regime finds features consistent with a loss of both C4 rotation and mirror symmetry in the electronic structure of the CuO2 planes in the pseudogap state.
Abstract: The presence of optical polarization anisotropies, such as Faraday or Kerr effects, linear birefringence, and magnetoelectric birefringence are evidence for broken symmetry states of matter. The recent discovery of a Kerr effect using near-IR light in the pseudogap phase of the cuprates can be regarded as a strong evidence for a spontaneous symmetry breaking and the existence of an anomalous long-range ordered state. In this work we present a high precision study of the polarimetry properties of the cuprates in the THz regime. While no Faraday effect was found in this frequency range to the limits of our experimental uncertainty (1.3 milli-radian or 0.07\ifmmode^\circ\else\textdegree\fi{}), a small but significant polarization rotation was detected that derives from an anomalous linear dichroism. In ${\mathrm{YBa}}_{2}{\mathrm{Cu}}_{3}{\mathrm{O}}_{y}$ the effect has a temperature onset that mirrors the pseudogap temperature ${T}^{*}$ and is enhanced in magnitude in underdoped samples. In $x=1/8$ ${\mathrm{La}}_{2\ensuremath{-}x}{\mathrm{Ba}}_{x}{\mathrm{CuO}}_{4}$, the effect onsets above room temperature, but shows a dramatic enhancement near a temperature scale known to be associated with spin- and charge-ordered states. These features are consistent with a loss of both ${C}_{4}$ rotation and mirror symmetry in the electronic structure of the ${\mathrm{CuO}}_{2}$ planes in the pseudogap state.
TL;DR: Clinicians and scientists recruiting for clinical studies should learn how to use online social media platforms to improve recruitment rates, thus increasing recruitment efficiency and cost-effectiveness.
Abstract: Background
Recruitment of women in the periconceptional period to clinical studies using traditional advertising through medical establishments is difficult and slow. Given the widespread use of the internet as a source for medical information and research, we analyze the impact of social media in the second phase of an ongoing randomized, open-label clinical trial among pregnant women. This study aims to assess the effectiveness of social media as a recruitment tool through the comparison of diverse recruitment techniques in two different phases of the trial.
Methods
Recruitment in Phase 1 of the study consisted solely of traditional healthcare-based sources. This was compared to Phase 2 of the study where traditional recruitment was continued and expanded, while social media was used as a supplementary source. Yearly recruitment and recruitment rates in the two phases were compared using the Mann Whitney U test. The contributions of each recruitment source to overall recruitment were analyzed, and the impact of potential confounders on recruitment rate was evaluated using a multiple regression and Interrupted Time Series Analysis.
Results
In the first phase of the study, with over 56 months of recruitment using traditional sources, 35 women were enrolled in the study, resulting in a mean rate of ±0.62 recruits/month. In the 6 months implementing recruitment through social media, 45 women were recruited, for a 12-fold higher rate of ±7.5 recruits/month. Attrition rates remained constant, suggesting that social media had a positive impact on recruitment. The Interrupted Time Series Analysis detected a significant difference in recruitment after the intervention of social media (p<0.0001) with an evident increase in the number of recruits observed after the use of social media.
Conclusions
Clinicians and scientists recruiting for clinical studies should learn how to use online social media platforms to improve recruitment rates, thus increasing recruitment efficiency and cost-effectiveness.
TL;DR: A large number of potentially beneficial uses of statins in pregnant women have prompted a new evaluation of the risk-benefit ratio of these agents in pregnancy, and a meta-analysis of controlled observational studies has failed to corroborate this.
Abstract: Although an initial case series suggested that use of statins in pregnancy carried teratogenic risk, a recent meta-analysis of controlled observational studies has failed to corroborate this. A large number of potentially beneficial uses of statins in pregnant women have prompted a new evaluation of the risk-benefit ratio of these agents in pregnancy.
TL;DR: Data suggest that, pending further study, dabigatran should not be used for anticoagulation of pregnant women, because the drug may have an adverse effect on fetal blood coagulation.
Journal Article•
TL;DR: Screening for the detection of T gondii is only performed in Nunavik and other parts of northern Quebec owing to the high prevalence of infection in this region and the high cost associated with testing.
Abstract: Question Congenital toxoplasmosis is a dangerous fetal infection. Why is routine screening for Toxoplasma gondii infection during pregnancy not available for most Canadians?
Answer Low prevalence of the infection, high cost associated with testing, low sensitivity of screening tests, false-positive test results, and limitations of treatment effectiveness are all cited as reasons for not routinely screening for T gondii infection in Canada. Currently, screening for the detection of T gondii is only performed in Nunavik and other parts of northern Quebec owing to the high prevalence of infection in this region. Congenital toxoplasmosis causes neurologic or ocular disease (leading to blindness), as well as cardiac and cerebral anomalies.
TL;DR: Hyperactive, hyperphosphorylated RyRs because of reduced local phosphatase activity enhance triggered activity in LQT2 syndrome, and EADs are promoted by aberrant RyR-mediated Ca2+ releases that are present despite a reduction of sarcoplasmic reticulum content.
Abstract: Rationale:Loss-of-function mutations in human ether go-go (HERG) potassium channels underlie long QT syndrome type 2 (LQT2) and are associated with fatal ventricular tachyarrhythmia. Previously, most studies focused on plasma membrane–related pathways involved in arrhythmogenesis in long QT syndrome, whereas proarrhythmic changes in intracellular Ca2+ handling remained unexplored. Objective:We investigated the remodeling of Ca2+ homeostasis in ventricular cardiomyocytes derived from transgenic rabbit model of LQT2 to determine whether these changes contribute to triggered activity in the form of early after depolarizations (EADs). Methods and Results:Confocal Ca2+ imaging revealed decrease in amplitude of Ca2+ transients and sarcoplasmic reticulum Ca2+ content in LQT2 myocytes. Experiments using sarcoplasmic reticulum–entrapped Ca2+ indicator demonstrated enhanced ryanodine receptor (RyR)–mediated sarcoplasmic reticulum Ca2+ leak in LQT2 cells. Western blot analyses showed increased phosphorylation of RyR...
Journal Article•
TL;DR: In this article, a high precision study of the polarimetry properties of the cuprates in the THz regime was presented, and it was shown that a small but significant polarization rotation was detected that derives from an anomalous linear dichroism.
Abstract: The presence of optical polarization anisotropies, such as Faraday or Kerr effects, linear birefringence, and magnetoelectric birefringence are evidence for broken symmetry states of matter. The recent discovery of a Kerr effect using near-IR light in the pseudogap phase of the cuprates can be regarded as a strong evidence for a spontaneous symmetry breaking and the existence of an anomalous long-range ordered state. In this work we present a high precision study of the polarimetry properties of the cuprates in the THz regime. While no Faraday effect was found in this frequency range to the limits of our experimental uncertainty (1.3 milli-radian or 0.07\ifmmode^\circ\else\textdegree\fi{}), a small but significant polarization rotation was detected that derives from an anomalous linear dichroism. In ${\mathrm{YBa}}_{2}{\mathrm{Cu}}_{3}{\mathrm{O}}_{y}$ the effect has a temperature onset that mirrors the pseudogap temperature ${T}^{*}$ and is enhanced in magnitude in underdoped samples. In $x=1/8$ ${\mathrm{La}}_{2\ensuremath{-}x}{\mathrm{Ba}}_{x}{\mathrm{CuO}}_{4}$, the effect onsets above room temperature, but shows a dramatic enhancement near a temperature scale known to be associated with spin- and charge-ordered states. These features are consistent with a loss of both ${C}_{4}$ rotation and mirror symmetry in the electronic structure of the ${\mathrm{CuO}}_{2}$ planes in the pseudogap state.
TL;DR: NVP is associated with favorable fetal outcome, and therefore studies of drug exposure in pregnancy should either match their exposed and control cases for existence and severity of NVP, or adjust for these confounders in their multivariate analysis.
TL;DR: Testing the hypotheses that activation of SK channels in ventricular myocytes requires Ca(2+) release from sarcoplasmic reticulum (SR) and that SK currents contribute to reducing triggered activity in HF concludes that SK upregulation in HF may have an anti-arrhythmic effect by reducing triggeredActivity.
Abstract: SK channels are upregulated in human patients and animal models of heart failure (HF). However, their activation mechanism and function in ventricular myocytes remain poorly understood. We aim to t...
TL;DR: A historical cohort study involving all women who conceived between January 2003 and December 2009 and who were admitted for delivery or spontaneous abortion found no increased risk of spontaneous abortion following exposure to NSAIDs.
Abstract: Background: Spontaneous abortion is the most common complication of pregnancy. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used during pregnancy. Published data are inconsistent regarding the risk of spontaneous abortion following exposure to NSAIDs. Methods: We performed a historical cohort study involving all women who conceived between January 2003 and December 2009 and who were admitted for delivery or spontaneous abortion at Soroka Medical Center, Clalit Health Services, Israel. A computerized database of medication dispensation was linked with 2 computerized databases containing information on births and spontaneous abortions. We constructed time-varying Cox regression models and adjusted for maternal age, diabetes mellitus, hypothyroidism, obesity, hypercoagulation or inflammatory conditions, recurrent miscarriage, in vitro fertilization of the current pregnancy, intrauterine contraceptive device, ethnic background, tobacco use and year of admission. Results: The cohort included 65 457 women who conceived during the study period; of these, 58 949 (90.1%) were admitted for a birth and 6508 (9.9%) for spontaneous abortion. A total of 4495 (6.9%) pregnant women were exposed to NSAIDs during the study period. Exposure to NSAIDs was not an independent risk factor for spontaneous abortion (nonselective cyclooxygenase [COX] inhibitors: adjusted hazard ratio [HR] 1.10, 95% confidence interval [CI] 0.99–1.22; selective COX-2 inhibitors: adjusted HR 1.43, 95% CI 0.79–2.59). There was no increased risk for specific NSAID drugs, except for a significantly increased risk with exposure to indomethacin (adjusted HR 2.8, 95% CI 1.70–4.69). We found no dose–response effect. Interpretation: We found no increased risk of spontaneous abortion following exposure to NSAIDs. Further research is needed to assess the risk following exposure to selective COX-2 inhibitors.
TL;DR: Preliminary findings suggest that smoking cessation intervention is associated with decreased hair cortisol levels and that reduced hair cortisol may be specifically associated with mindfulness training and smoking abstinence and support the use of hair cortisol as a novel objective biomarker in future research.
Abstract: Objectives: Stress is a well-known predictor of smoking relapse, and cortisol is a primary biomarker of stress. The current pilot study examined changes in levels of cortisol in hair within the context of two time-intensity matched behavioral smoking cessation treatments: mindfulness training for smokers and a cognitive-behavioral comparison group. Participants: Eighteen participants were recruited from a larger randomized controlled trial of smoking cessation. Outcome Measures: Hair samples (3 cm) were obtained 1 month after quit attempt, allowing for a retrospective analysis of hair cortisol at preintervention and post–quit attempt time periods. Self-reported negative affect was also assessed before and after treatment. Intervention: Both groups received a 7-week intensive intervention using mindfulness or cognitive-behavioral strategies. Results: Cortisol significantly decreased from baseline to 1 month after quit attempt in the entire sample (d=−0.35; p=.005). In subsequent repeated-measures ...
TL;DR: The hair C/T ratio was significantly correlated with age, BMI and waist circumference better than hair cortisol or testosterone alone and the measurement of hormones in hair is a useful tool in research and possibly clinical practice.
Abstract: Objective: Hair analysis has been demonstrated to accurately reflect exposure to drug abuse, environmental toxins and exogenous hormones. We tested the feasibility of measuring cortisol and testosterone in hair of healthy and obese subjects. Measurements: A modified immunoassay (ELISA) originally developed for saliva was used. Hair, urine and blood samples were collected from young non-obese and obese patients. Perceived stress (PSS) was measured using a validated questionnaire. Results: There was no difference in PSS between non-obese and obese subjects. Hair cortisol levels were significantly correlated with weight (r=0.27, p Conclusion: Hair cortisol levels increase, while hair testosterone levels decrease with obesity. The hair C/T ratio was significantly correlated with age, BMI and waist circumference better than hair cortisol or testosterone alone. As hair collection is non-invasive and is not influenced by moment-to-moment variations, the measurement of hormones in hair is a useful tool in research and possibly clinical practice.
TL;DR: Human and rat hair PBDE measurements correlate strongly with those in alternative matrices, validating the use of hair as a noninvasive biomarker of long-term PBDE exposure.
Abstract: The efficacy of using hair as a biomarker for exposure to polybrominated diphenyl ether (PBDE) flame retardants was assessed in humans and an animal model. Paired human hair and serum samples were obtained from adult men and women (n = 50). In parallel, hair, serum, liver, and fat were collected from adult male Sprague-Dawley rats exposed to increasing doses of the PBDE mixture found in house dust for 70 days via the diet. All samples were analyzed by GC-MS for eight common PBDEs: BDE-28, -47, -99, -100, -153, -154, -183, and -209. Paired human hair and serum samples had five congeners (BDE-28, -47, -99, -100, and -154) with significant individual correlations (0.345-0.566). In rat samples, BDE-28 and BDE-183 were frequently below the level of detection. Significant correlations were observed for BDE-47, -99, -100, -153, -154, and -209 in rat hair, serum, liver, and fat across doses, with r values ranging from 0.803 to 0.988; weaker correlations were observed between hair and other tissues when data from the lowest dose group or for BDE-209 were analyzed. Thus, human and rat hair PBDE measurements correlate strongly with those in alternative matrices, validating the use of hair as a noninvasive biomarker of long-term PBDE exposure.
TL;DR: The literature on SSRIs in pregnancy is somewhat confusing but when analysing all prospective cohort data there seems to be no demonstrable increase in the rate of major anomalies or developmental disorders, and the risk associated with treatment discontinuation appears to outweigh the potential, unproven risks of treatment.
Abstract: There has been an increase in the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy. However, in the last 10 years, in spite of a vast literature regarding use in pregnancy there seems to be some confusion as to the possible risk of these drugs, especially related to cardiovascular anomalies. In addition, there are data on developmental follow-up studies that raise the question of possible slight developmental and neurobehavioral problems. The purpose of the present review is therefore to critically summarize the current evidence for the risk/benefit analysis of SSRI use in human pregnancy. Although most studies have not shown an increase in the overall risk of major malformations, several have suggested that the use of SSRIs may be associated with a small increased risk for cardiovascular malformations. However, new compelling evidence shows that this apparent increased risk occurs also in women with untreated depression, highlighting the probable ascertainment bias involved in many of these studies. Persistent pulmonary hypertension of the newborn (PPHN) has also been described with an absolute risk of <1%; however, here too, higher rates were described among offspring of women with untreated depression. Poor neonatal adaptation has been described in up to 30% of neonates exposed to SSRIs late in pregnancy. Of the few postnatal developmental follow-up studies, there are no significant developmental problems. The literature on SSRIs in pregnancy is somewhat confusing but when analysing all prospective cohort data there seems to be no demonstrable increase in the rate of major anomalies or developmental disorders. When evaluating the risk/benefit ratio of SSRI treatment in pregnancy, the risk associated with treatment discontinuation - e.g. higher frequency of relapse, increased risk of preterm delivery and postpartum depression - appear to outweigh the potential, unproven risks of treatment. Moreover, maternal depression may negatively affect the child's development, emphasizing the importance of prevention by appropriate treatment during pregnancy with the least minimal effective dose.
TL;DR: A range of effects, including physical, mental, behavioral, and/or learning disabilities, that can affect a person's quality of life are studied.
Abstract: A range of effects, including physical, mental, behavioral, and/or learning disabilities, that can o…
Journal Article•
TL;DR: The current available information does not suggest that tacrolimus increases the risk of major congenital malformations above the baseline risk in the general population, but as there are some reports of hyperkalemia and renal impairment in infants exposed to tacolimus in utero, kidney function and electrolytes should be monitored in exposed neonates.
Abstract: Question I have a 30-year-old patient who had a kidney transplant 2 years ago. She is now planning a pregnancy. She has been treated with tacrolimus since her transplant. Will it be safe for the fetus if she continues to take it during the pregnancy or should she switch to a different antirejection medication?
Answer If your patient is stable while taking tacrolimus, there is no reason to switch. The current available information does not suggest that tacrolimus increases the risk of major congenital malformations above the baseline risk in the general population. Premature birth and low birth weight are often reported in this population; however, these effects are frequently reported in pregnant transplant patients treated with other immunosuppressant agents and probably reflect the effects of the maternal condition. As there are some reports of hyperkalemia and renal impairment in infants exposed to tacrolimus in utero, kidney function and electrolytes should be monitored in exposed neonates.
TL;DR: Exposure to SSRIs/SNRIs during gestational week 30 to childbirth did not confer any increased risk of postpartum hemorrhage after vaginal or cesarean delivery, and use of antidepressants in pregnancy was not associated with any obstetrical bleeding outcome.
Abstract: This study aimed to examine obstetric bleeding outcomes after exposure during pregnancy to selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic (TCAs), and other antidepressants (OADs).The Norwegian Mother and Child Cohort Study and the Medical Birth Registry of Norway constituted the data source for the present study. We included 57,279 pregnant women, of which 1.02% reported use of antidepressants during pregnancy, mostly SSRIs/SNRIs (0.92%). We categorized exposure according to antidepressant use in pregnancy (SSRIs/SNRIs, n = 527; TCAs/OADs, n = 59; nonexposed, nondepressed, n = 55,411) with inclusion of a disease comparison group (nonexposed, depressed, n = 1282). We used logistic regression to estimate adjusted odds ratio (aOR) and 95% confidence interval (CI) for vaginal bleeding outcomes in pregnancy and postpartum hemorrhage.Compared with nonexposed subjects, first trimester exposure to SSRIs/SNRIs or TCAs/OADs did not confer any increased risk of vaginal bleeding in early pregnancy (aOR, 0.91; 95% CI, 0.72-1.16 and aOR, 0.83; 95% CI, 0.36-1.92, respectively). No increased risk for vaginal bleeding in midpregnancy was observed among users of SSRIs/SNRIs (aOR, 0.81; 95% CI, 0.50-1.31) or TCAs/OADs (aOR, 0.96; 95% CI, 0.26-3.53) in second trimester. Exposure to SSRIs/SNRIs during gestational week 30 to childbirth did not confer any increased risk of postpartum hemorrhage after vaginal (aOR, 0.90; 95% CI, 0.47-1.74) or cesarean (aOR, 1.47; 95% CI, 0.51-4.22) delivery. Women in the disease comparison group presented a significant moderate increased risk of vaginal bleeding in early pregnancy (aOR, 1.22; 95% CI, 1.06-1.39) and midpregnancy (aOR, 1.28; 95% CI, 1.07-1.55) but not postpartum.Among this Norwegian cohort of pregnant women, use of antidepressants in pregnancy was not associated with any obstetrical bleeding outcome.
TL;DR: In this small cohort of pediatric kidney transplant recipients, POR*28 genotype seems to explain part of the variability found in tacrolimus disposition, in addition to age and CYP3A5 genotype.
Abstract: BACKGROUND:: Both age and CYP3A5 genotype are important determinants of tacrolimus disposition in pediatric kidney transplant recipients. In a recent study in adults, POR*28 was associated with increased dosing requirements early after transplant of CYP3A5-expressing kidney transplant recipients. The authors aimed to evaluate the additional contribution of POR*28 to early tacrolimus disposition in pediatric kidney transplant recipients. METHODS:: Retrospective data of 43 pediatric kidney transplant recipients up to 14 days posttransplant were evaluated on tacrolimus dose and tacrolimus predose blood concentrations. Recipient POR*28 and CYP3A5 genotype were determined. RESULTS:: CYP3A5 expressers carrying at least 1 POR*28 allele had on average 18.3% lower tacrolimus predose concentrations and 20.2% lower concentration/dose ratios compared with CYP3A5 expressers with POR*1/*1 genotype (P = 0.002 and P = 0.001, respectively). In CYP3A5 nonexpressers, tacrolimus disposition did not significantly differ between POR genotypes. CONCLUSIONS:: In this small cohort of pediatric kidney transplant recipients, POR*28 genotype seems to explain part of the variability found in tacrolimus disposition, in addition to age and CYP3A5 genotype. This finding should be validated in a larger population, and it would be worthwhile to evaluate the clinical impact of this genotype.